1 the official journal of the fall clinical and winter clinical dermatology conferences welcome to volume 2, issue 1 of skin: the journal of cutaneous medicinetm. we thank you, the readership of skin, for all of your feedback and suggestions. as a journal made by dermatologists for dermatologists, we are constantly looking for ways to implement new features aimed at serving the needs of the dermatology community. our featured article is selected by the editorial team due to the timeliness and pertinence of the information provided within. we are pleased to announce the featured article for volume 2, issue 1, “risk factors for the development of acute radiation dermatitis in breast cancer patients” by jennifer parker, md, et. al. we believe that this article will provide practical information for the practicing dermatologist. one of our goals at skin is to incorporate the use of technology in order to aid in the widespread dissemination of dermatologic knowledge. with this spirit in mind, we are excited to announce the inclusion of 2 videos of cme lectures presented at the 2017 fall clinical dermatology conference®. this issue includes two such videos: “what’s new in the medicine chest, part 2” by james del rosso, do, and “the newest in dermatology” by joshua zeichner, md. the editors of skin hope that you will find the knowledge contained in this issue to be of value. as always, we look forward to your thoughts and ideas of how we can continue to make skin optimize its value to you. editors-in-chief mark lebwohl md professor and chairman, dermatology, icahn school of medicine at mount sinai, new york roger ceilley md clinical professor of dermatology, university of iowa school of medicine, des moines, ia james del rosso do adjunct clinical professor, touro university college of osteopathic medicine, henderson, nv introduction results conclusions methods objective subjects study design assessments tm weber,1 ce arrowitz,1 u scherdin,2 am schoelermann,2 a filbry2 1beiersdorf inc, wilton, ct, usa; 2beiersdorf ag, hamburg, germany a moisturizing spray ointment to help alleviate dry skin symptoms associated with atopic eczema, psoriasis, and xerosis figure 1. figure 2. figure 3. figure 4. figure 5. 55% 6% 35% 2% atopic eczema xerosis psoriasis ichthyosis n=80 2.29 1.61 0.34 0.86 0.51 0.13 0 0.5 1.0 1.5 2.0 2.5 dryness scaling cracks m ea n c lin ic al g ra d in g s co re * * * obs=aquaphor ointment body spray *p<0.0001 vs baseline n=80 baseline end of study 0 20 40 60 severe/ very severe moderate slight none severe/ very severe moderate slight none severe/ very severe moderate slight none 0 20 40 60 0 25 50 75 reduction in dryness reduction in scaling reduction in cracks n=70 n=20 end of study 0.59 1.39 1.39 1.1 0.15 0.81 0.41 0.39 0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 burning erythema itching tightness m ea n c lin ic al g ra d in g s co re * * * * obs=aquaphor ointment body spray *p<0.0001 vs baseline n=80 baseline end of study reduction in itching reduction in erythema 0 20 40 60 0 20 40 60 % o f su b je ct s % o f su b je ct s n=62 n=57 reduction in burning reduction in tightness obs=aquaphor ointment body spray mean duration of treatment=16.2 days % o f su b je ct s % o f su b je ct s 0 20 40 60 0 20 40 60 80 n=35 n=52 severe/ very severe moderate slight none severe/ very severe moderate slight none severe/ very severe moderate slight none severe/ very severe moderate slight none progression to reduced symptom severity baseline end of study p p fc17posterbeiersdorfwebermoisturizingspray.pdf skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 402 research letter low rate of keloid recurrences following treatment of keloidectomy sites with a biologically effective dose 30 of superficial radiation brian berman md, phd1, mark s. nestor md, phd1, michael h. gold md2, david j. goldberg md, jd3, joshua fox md4, george schmieder do5 1center for clinical & cosmetic research, aventura, fl 2gold skin care center, nashville, tn 3skin laser & surgery specialists of ny/nj 4advanced dermatology, ny, ny 5park avenue dermatology, orange park, fl the potential for recurrence of keloids at the sites of previously excised keloids is a wellrecognized consequence following keloidectomy, and based on the published literature, has been reported to occur approximately in 71% of cases.1 superficial radiation reduces wound fibroblast proliferation and enhances apoptosis.2 in this multi-center, case series, we determine the recurrence rate of keloids post keloidectomy with peri-operative treatment with a biologically effective dose 30 of superficial radiation.3 297 keloids were surgically completely excised. starting on post-operative day (pod) 1 the suture closure line, with a 5 mm margin, received a total biologically effective dose 30 (bed 30), either 70 kv or 100 kv, of superficial radiation delivered by an srt-100 (figure 1). one of the following superficial radiation bed 30 fractionation protocols was employed post keloidectomy: one fraction of 13 gy on post-operative day 1; or 2 fractions of 8 gy on post-operative days 1 and 2; or, in the majority of cases, 3 fractions of 6 gy on post-operative days 1, 2 and 3. radiation dermatitis was not reported. the most common adverse local skin reaction was transient (3-6 months) hyperpigmentation, occurring in fitzpatrick skin type v-vi individuals. hypopigmentation was noted to occur rarely. the follow-up period ranged from 1 month to 3 years, with the majority having been followed for more than 1 year. there were 9 clinical keloid recurrences in the 297 keloidectomy sites for a recurrence rate of 3.0%. the observed 3.0% rate of keloid recurrence following surgical keloidectomy and treatment of the excision site with superficial radiation therapy (bed 30) is markedly lower than that reported in the literature following keloid excision alone. a prospective study, with longer follow-up to assess any long term adverse events and late recurrences, is warranted. skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 403 a) baseline. b) postexcision. c) srt 6gy x 3 sessions. d) 6 months post treatment. e) 12 months post treatment. conflict of interest disclosures: drs. berman, nestor, gold, and goldberg are consultants for sensus healthcare. funding: sensus healthcare funded the $400 institutional review board submission fee. . corresponding author: brian berman, md, phd 2925 aventura boulevard, suite 205 aventura, fl email: bbmdphd@gmail.com references: 1. mustoe ta, cooter rd, gold mh, hobbs fd, ramelet aa, shakespeare pg et al. international advisory panel on scar management. international clinical recommendations on scar management. plast reconstr surg 2002; 110: 560–571 2. liu x1, liu jz, zhang e, li p, zhou p, cheng tm, zhou yg. impaired wound healing after local soft x-ray irradiation in rat skin: time course study of pathology, proliferation, cell cycle, and apoptosis. j trauma. 2005 sep;59(3):682-90. 3. kal hb and veen re. biologically effective doses of postoperative radiotherapy in the prevention of keloids. dose-effect relationship. strahlentherapie und onkologie november 2005, volume 181, issue 11, pp 717–7 a b c d e mailto:bbmdphd@gmail.com https://link.springer.com/journal/66 https://link.springer.com/journal/66 https://link.springer.com/journal/66 https://link.springer.com/journal/66 https://link.springer.com/journal/66/181/11/page/1 skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 958 compelling comments xylazine: an ulcerating addiction kripa ahuja ms1, grace desena ba2 1 eastern virginia medical school, norfolk, va 2 the university of florida college of medicine, gainesville, fl xylazine, a muscle relaxant typically used as a horse tranquilizer, has recently found its way to the us drug market.1 there are increasing cases of xylazine-laced fentanyl, further exacerbating the opioid epidemic.1–3 while efforts to combat this new drug issue are underway, dermatologists should be aware of the complications arising from xylazine. regular use of xylazine has been associated with the formation of skin ulcers.13 though the mechanism of action is incompletely understood, a possible pathophysiology may be rooted in xylazine’s role as an alpha-2-agonist.1–3 cutaneously, xylazine functions as a vasoconstrictor, which can drastically reduce skin perfusion and impair wound healing.3 when an ulcer initially forms, it is painful, which may prompt users to continually inject at the site of the ulcer in an attempt to decrease pain, further exacerbating the ulcer.2 the deleterious cycle of vasoconstriction and repeated injection may account for the high infection rate seen with these ulcers, which can even progress to necrosis.1–3 xylazine lesions can develop over areas of the body deprived of intravenous injection, thus providers should not only examine injection sites.4 xylazine ulcers have had a wide characterization, from a sole oval retiform purpuric plaque to extensive necrotic ulcerations.1,3 biopsies have demonstrated epidermal necrosis with focal fibrin thrombi, nonspecific inflammation, and subcutaneous necrosis.1 xylazine-induced skin ulcers are a serious pathology that dermatologists should consider in any patient with a history of iv drug use. the american academy of dermatology (aad) recommends practicing multidisciplinary care including addiction specialists, infectious disease physicians, wound care experts, as well as plastic surgeons.4 a skin biopsy may be warranted if there is a high suspicion of other causes of ulceration (squamous cell carcinoma, pyoderma gangrenosum, etc), though it is not mandatory. the aad does however recommend wound cultures.4 advanced laboratory techniques such as thin-layer chromatography or gas chromatographymass spectrometer can detect xylazine, though these testing modalities are not routinely employed in routine practice.4 thus, xylazine-induced skin ulcers is a clinical diagnosis.4 the limited data on xylazine-skin ulcers have reported improvement from consistent, local wound care, though this is an area necessitating greater exploration.1–4 in less than a decade, xylazine rose from being involved in 2% of fatal heroin and/or fentanyl overdoses to 31%.2,4 concerted efforts are necessary to prevent xylazineinduced pathology. for the time being, skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 959 dermatologists should be increasingly aware of xylazine-skin ulcers, especially in philadelphia, maryland, and connecticut, as these areas have the highest reported prevalence of xylazine.4 conflict of interest disclosures: none funding: none corresponding author: kripa raj ahuja 825 fairfax avenue, norfolk, va 23507 phone: (407) 417-1983 email: ahujak@evms.edu references: 1. rose l, kirven r, tyler k, chung c, korman am. xylazine-induced acute skin necrosis in two patients who inject fentanyl. jaad case rep. 2023;36:113-115. doi:10.1016/j.jdcr.2023.04.010 2. johnson j, pizzicato l, johnson c, viner k. increasing presence of xylazine in heroin and/or fentanyl deaths, philadelphia, pennsylvania, 2010–2019. inj prev. 2021;27(4):395-398. doi:10.1136/injuryprev-2020-043968 3. malayala sv, papudesi bn, bobb r, wimbush a. xylazine-induced skin ulcers in a person who injects drugs in philadelphia, pennsylvania, usa. cureus. published online august 19, 2022. doi:10.7759/cureus.28160 4. heymann, warren. xylazine (“tranq”): the potential for loss of life and limb. american academy of dermatology association. published december 7, 2022. https://www.aad.org/dw/dw-insights-andinquiries/archive/2022/xylazine-potential-for-lossof-life-and-limb skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 620 short communications eccrine porocarcinoma masquerading as squamous cell carcinoma drew kuraitis, md, phd1, yong lee, bs2, abida kadi3, andrea murina, md1 1department of dermatology, tulane university, new orleans, la 2tulane university school of medicine, tulane university, new orleans, la 3department of pathology, tulane university, new orleans, la a squamoid variant of eccrine porocarcinoma (epc) exists and is often misdiagnosed as squamous cell carcinoma (scc) due to clinical and histopathologic similarities. in this report, we present two cases of presumed scc based on biopsy findings, later diagnosed as epc after tumor excision. case 1 a 70-year old caucasian man with a history of neurofibromatosis type i presented with an asymptomatic hyperkeratotic erythematous papule of unknown duration to his upper back (fig 1). shave biopsy revealed invasive, moderately differentiated squamous cell carcinoma (scc; fig 2a). after subsequent excision, the specimen was read as moderately-to-poorly differentiated carcinoma with eccrine ductal differentiation (fig 2b). case 2 a 64-year old caucasian man presented with a 5-year history of an ulcerated hyperkeratotic plaque to his posterior pinna (no clinical photo). shave biopsy revealed scc (figure 3a). after subsequent excision, the specimen was read as poorly differentiated porocarcinoma (figure 3b). figure 1. hyperkeratotic erythematous papule diagnosed as squamous cell carcinoma on biopsy, later diagnosed as eccrine porocarcinoma after excision. in both of these cases, scc diagnosis was rendered based on shave biopsy specimen, but later changed to eccrine porocarcinoma that after excision. there are reports of a introduction case presentation discussion skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 621 figure 2. tumor diagnosed as squamous cell carcinoma on shave biopsy from case 1 (a). the tumor is composed of squamous and basaloid cells and shows continuity with the epidermis. no apparent poroid differentiation. tumor re-diagnosed as porocarcinoma after excision (b). the tumor exhibits anastamosing trabecular growth pattern with ductal differentiation within the dermis. the tumor cells have pleomorphic and vesicular nuclei. squamous variant of epc histopathologically mimics scc or scc in situ, although this presentation is thought to be quite rare. this squamous variant has been characterized in a retrospective study of 21 cases.1 features that favor the diagnosis of squamous epc include tumor cells within the dermis in anastomosing trabeculae and ductal structures lined by tumor cells. although these features were seen on excised specimens, the initial shave biopsies performed on our patients did not allow for assessment of these characteristics, likely lending to the diagnosis of scc. accurate diagnosis of epc is imperative for proper medical management. compared to figure 3. tumor diagnosed as squamous cell carcinoma on shave biopsy from case 2 (a). the lesion shows features of moderately differentiated invasive squamous cell carcinoma, with pleomorphism, increase mitotic activity and keratinization. tumor re-diagnosed as porocarcinoma after excision (b). the tumor is composed of basaloid cells with intracytoplasmic lumina/duct formation and focal keratinization. it has a broadpushing lower borders which are sharply delineated. skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 622 cutaneous scc, epcs have higher rates of local recurrence (20%), regional recurrence (20%), distant metastasis (12%) and mortality (65% with nodal involvement).2 non-surgical scc in situ treatments (topical chemotherapy, electrodessication and curettage) of epc masquerading as scc in situ would be insufficient, likely contributing to delay of appropriate care and poor outcomes. after reviewing our shave biopsy and excision specimens, the diagnosis of epc would have been made if the initial shave biopsies from both cases had deeper dermal sampling. we wish to call attention to the existence of the squamous epc variant, in addition to highlighting the diagnostic difficulty that these lesions may present, as squamous epc variants and squamous cell malignancies may have similar clinical and histopathologic appearance, especially if sampling via shave biopsy provides little dermal tissue for examination. conflict of interest disclosures: none funding: none corresponding author: drew kuraitis 1430 tulane avenue #8036 new orleans, la 70112 phone: 504-988-5114 email: dkuraiti@tulane.edu references: 1. mahomed f, blok j, grayson w. the squamous variant of eccrine porocarcinoma: a clinicopathological study of 21 cases. j clin pathol. 2008;61(3):361-365. 2. 2. snow sn, reizner gt. eccrine porocarcinoma of the face. j am acad dermatol. 1992;27(2 pt 2):306-311. conclusion acknowledgements: this study was funded by ortho dermatologics. medical writing support was provided by prescott medical communications group (chicago, il) with financial support from ortho dermatologics; ortho dermatologics is a division of bausch health us, llc • presented at fall clinical 2020 • october 29 november 1, 2020 • virtual synopsis ◾ the ability of a topical medication to spread is an important parameter, since only the thinnest layer of medication contacting the skin is physiologically active ◾ a thinner film is just as effective as a thicker film from an efficacy standpoint, but a thinner film will spread farther—exhibiting superior spreadability and increasing the number of applications while decreasing the cost per application ◾ from a rheological perspective, products exhibiting low yield stress and lower intrinsic viscosity will have better spreadability and require less effort to spread at the surface of the skin1,2 • yield stress is the minimum force required to make a structured fluid flow • viscosity describes a fluid’s resistance to flow (eg, the “thickness” of a fluid) objective ◾ to compare the spreadability of two topical formulations: tazarotene 0.045% polymeric emulsion lotion versus trifarotene 0.005% cream ◾ to relate the rheological profile of topical products to their spreadability methods ◾ this double-blind, split-body study enrolled male or female adults ≥18 years of age with normal back skin • participants, who provided written informed consent, were assessed for limited back hair which would prevent application of the study products ◾ tazarotene 0.045% lotion was applied to one randomized half of the back and trifarotene 0.005% cream was applied to the opposite randomized half of the back (figure 1) • the back was divided at the vertebral column into right and left • drugs were randomized for right or left application; however, the left back product was always pigmented blue and the right back product was always pigmented green. one toothpick tip of blue or green food-coloring gel was used to pigment the drugs a comparative clinical demonstration of the spreadability of tazarotene lotion 0.045% versus trifarotene cream 0.005% ◾ the blinded dermatologist investigator was presented with 0.1 cc (0.1 ml) of each of the drugs for application by the unblinded coordinator ◾ two 10 cm wide application areas were marked with a gentian violet marker, one on each side of the back; this mark defined the lateral bounds over which the lotion or cream were spread ◾ the investigator applied the products with a gloved hand to obtain an even film, moving study product down the back until it would no longer spread ◾ the lower extent of the study product application was marked with a gentian violet marker and measured in centimeters ◾ a two-tailed student’s t-test was used to assess the spreadability data figure 1. study schematic tazarotene 0.045% lotion and trifarotene 0.005% cream randomized 1:1 left side of back 10 cm right side of back 10 cm a p p lic at io n ar e a • spread 0.1 cc of lotion and cream down the back • measure area covered zoe d draelos, md1; emil a tanghetti, md2 1dermatology consulting services, pllc, high point, north carolina; 2center for dermatology and laser surgery, sacramento, ca figure 3. spreadability of tazarotene 0.045% lotion and trifarotene 0.005% cream on a participant conclusions ◾ the tazarotene 0.045% lotion spread on average 36.7 square centimeters farther than the trifarotene 0.005% cream ◾ these results are supported by the differences in the rheological profiles of the two products, in which tazarotene lotion exhibits lower yield stress and lower intrinsic viscosity versus trifarotene cream3 references 1. adeyeye mc, et al. aaps pharmscitech. 2002;3(2):e8. 2. kryscio dr, et al. aaps pharmscitech. 2008;9(1):84-86. 3. data on file. ortho dermatologics. author disclosures zdd received funding from ortho dermatologics to conduct the research presented in this poster. eat has served as speaker for novartis, ortho dermatologics, sun pharmaceuticals, lilly, galderma, abbvie, and dermira; served as a consultant/clinical studies for hologic, ortho dermatologics, and galderma; and is a stockholder for accure. results ◾ a total of 30 participants were included in the study ◾ participants ranged from 18 to 59 years of age; 26 (87%) were female ◾ tazarotene 0.045% lotion spread over an average area measuring 10 cm x 16.70 cm (167.0 cm2) while the trifarotene 0.005% cream spread over an average area measuring 10 cm x 13.03 cm (130.3 cm2; p<0.001; figure 2) ◾ no adverse reactions or adverse events occurred during the conduct of the study figure 2. mean spreadability of tazarotene 0.045% lotion and trifarotene 0.005% cream (n=30) 160 #( 0 40 80 120 167.0 tazarotene 0.045% lotion m e a n a re a o f p ro d u ct s p re a d ( cm 2 ) 130.3 #( 200 trifarotene 0.005% cream ***p<0.001 vs trifarotene. powerpoint presentation conclusions • in a subset of only adolescent subjects (9 to 17 years of age) treated with topical sb204 4% once-daily, there was a statistically significant reduction (p<0.05) in inflammatory, non-inflammatory and total lesion reductions with sb204 4% compared to vehicle • the percent change from baseline in the number of non-inflammatory lesions was -33.4% for sb204 and -24.2% for vehicle (p=0.0013) • the percent change from baseline in the number of inflammatory lesions was -43.4% for sb204 and 36.4% for vehicle (p=0.0113) • the percent change from baseline in the number of total lesions was -37.4% for sb204 and -29.1% for vehicle (p<0.001) • statistical significance was achieved for iga assessment of 2-grade change from baseline • all doses of sb204 administered in the studies were well tolerated and the adverse event profile was similar in active and vehicle treated subjects efficacy, tolerability and safety of sb204 gel in adolescents (9 to 17 years of age) with acne vulgaris diane thiboutot1, andrea zaenglein2, adelaide hebert3, lawrence eichenfield4 1department of dermatology, penn state hershey medical center, hershey, pa, 2department of dermatology and pediatrics, penn state hershey medical center, hershey, pa, 3department of dermatology, the university of texas medical school, houston, tx, 4department of dermatology, university of california, san diego, ca • sb204, a nitric oxide-releasing topical drug candidate, is in development for the treatment of acne vulgaris • sb204 was previously evaluated in two replicate, multi-center, randomized, double-blinded, vehicle-controlled, parallel group trials with >2600 subjects with moderate-to-severe acne (ni-ac301 and ni-ac302) • acne vulgaris is a common skin disease in adolescents • a post hoc analysis was conducted on a subset of 905 adolescents ranging from ages 9 to 17 years old • sb204 has potential immunomodulating and broad-spectrum antimicrobial activity introduction demographics tolerability results representative clinical photos from sb204 4% treatment group immunomodulatory activity of nitric oxide in acne nitric oxide inhibits the nlrp3 inflammasome, decreasing the downstream release of il-1β and il-17, as well as, kills p. acnes mchale k. effects of sb204 on lps-induced cytokine release in an ex-vivo human skin model. presented at 2017 dermatology summer symposium of the alabama dermatology society. mishra b et al. nitric oxide controls the immunopathology of tuberculosis by inhibiting nlrp3 inflammasome–dependent processing of il-1β. nature immunology. 2013;14:52-60. niedbala w et al. regulation of type 17 helper t-cell function by nitric oxide during inflammation proc natl acad sci usa. 2011;108(22):9220-9225. niedbala w et al. nitric oxide-induced regulatory t cells inhibit th17 but not th1 cell differentiation and function. j immunol. 2013;191(1):164-170. qin m et al. nitric oxide releasing nanoparticles prevent propionibacterium acnes induced inflammation by both clearing the organism and inhibiting microbial stimulation of the innate immune response. j invest dermatol. 2015;135(11):2723-2731. randomized (n = 905; 9 to 17 years of age) 12 weeks sb204 4% gel once daily (n [pooled] = 439) vehicle gel once daily (n [pooled] = 466) • sb204 4% gel (~900mg) or vehicle (~900mg) were applied once daily to the entire face • efficacy endpoints assessed: • absolute change in inflammatory, noninflammatory and total lesion counts from baseline to week 12 • success on investigator’s global assessment (iga) at week 12 (iga success was defined as a score of clear (0) or almost clear (1) and ≥2 grades less than baseline) baseline week 12 ni-ac301 and ni-ac302 sb204 4% (n, pooled = 439) vehicle (n, pooled = 466) gender, n male 228 (52%) 255 (55%) female 211 (48%) 211 (45%) age, mean 14 14 baseline, mean (sd) inflammatory lesion count 28 (5.7) 28 (5.9) non-inflammatory lesion count 42 (13) 42 (13) total lesions 70 (15) 70 (16) baseline iga scores “moderate” or a score of 3 377 (86%) 401 (86%) “severe” or a score of 4 62 (14%) 65 (14%) disposition, n completed 397 (90%) 421 (90%) discontinued 42 (10%) 45 (10%) study overview efficacy results treatment emergent adverse events (teaes) *p-values are based on analysis of covariance, using locf imputation (itt population) *p-values are based on analysis of covariance, using locf imputation (itt population) ni-ac301/302 n overall incidence (%) # of aes dermatitis dryness erythema exfoliation pain sb204 4% 23 1 (0.23%) 3 (0.68%) 2 (0.46%) 1 (0.23%) 7 (1.59%) vehicle 15 0 (0.0%) 1 (0.21%) 3 (0.64%) 2 (0.43%) 5 (1.07%) pruritus rash reaction swelling malaise pyrexia sb204 4% 3 (0.68%) 2 (0.46%) 1 (0.23%) 1 (0.23%) 1 (0.23%) 1 (0.23%) vehicle 2 (0.43%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 1 (0.21%) investigator global assessment scoring grade description 0 clear: clear skin with no inflammatory or non-inflammatory lesions 1 almost clear: rare non-inflammatory lesions with rare papules (papules may be resolving and hyperpigmented, though not pink-red) 2 mild: some non-inflammatory lesions with no more than a few inflammatory lesions 3 moderate: up to many non-inflammatory lesions and may have some inflammatory lesions, but no more than one nodulocystic lesion 4 severe: up to many non-inflammatory and inflammatory lesions, but no more than a few nodulocystic lesions post-hoc analysis conducted by iqvia powerpoint presentation background • a 31-gene expression profile (gep) test which identifies cutaneous melanoma tumors as low risk (class 1) or high risk (class 2) of metastasis has been clinically validated.1-3 • the test has been shown to influence physicians to direct clinical management of cutaneous melanoma patients in several clinical use studies (table 1).4-6 • to further assess the clinical impact of the gep test, we undertook a study to evaluate and compare clinical management plans prospectively, including initial workup, follow-up intervals, and referral patterns, established by physicians prior to and after gep testing. • here we present preliminary results of this multicenter, prospective clinical utility study to determine the clinical impact of the gep test on patient management plans. methods • of 269 patients enrolled in the study, 247 patients from 16 dermatology, medical oncology and surgical oncology centers had complete data at time of censoring (september 30, 2017). • the rt-pcr-based gep test was performed using primary melanoma tumor tissue from ffpe samples. the test provides a binary classification for risk of metastasis, class 1 (low risk) or class 2 (highrisk), using a proprietary predictive modeling algorithm. • at initial evaluation, prior to gep testing, each patient’s pre-test management recommendations were collected, including laboratory tests (labs), imaging, clinical visits, adjuvant treatment discussion, and referral to surgical or medical oncology. • post-test management recommendations were collected at the subsequent visit following receipt of gep test result. • preand post-test management plans were compared and changes were categorized as increase, decrease, or inconclusive. table 4. frequency of each modality of change in class 2 patients with decreases or increases in intensity of clinical management results table 2. cohort demographics conclusions • overall, 49% of tested patients had a change in clinical management. • the majority of reported management changes were in a riskappropriate direction, with 91% of decreases in care provided to low-risk class 1 patients and 72% of increases in care provided to high-risk class 2 patients. • physicians used gep results to individualize management based on biological risk, as determined by the test, while still remaining within the context of established practice guidelines. • results of this prospective study show that the accurate identification of risk provided by the gep informs appropriate clinical management and patient care. the proportion of patients in which the test informs change in management is similar to that reported in three additional clinical utility studies.4-6 references 1. gerami p, cook rw, russell mc, et al. clin cancer res 2015;21:175-83. 2. gerami p, cook rw, wilkinson j, et al. j am acad dermatol 2015;72:780-5 e783. 3. zager js, messina j, sondak vk, et al. j clin oncol 2016;34:9581. 4. berger ac, davidson rs, poitras jk, et al. curr med res opin 201632:1599-604. 5. farberg as, glazer am, white r, rigel ds. j drugs dermatol 2017;16:428-31. 6. schuitevoerder d, heath m, massimino k, et al. ann surg oncol 2017;24:s144. disclosures cj, kc and fam are employees and stockholders of castle biosciences, inc. the proprietary gep test is clinically available through castle biosciences as the decisiondx®melanoma test (www.skinmelanoma.com). clinical impact of a 31-gene expression profile test on physician recommendations for management of melanoma patients in a prospectively tested cohort martin fleming, md1, clare johnson, rn2, kyle covington, phd2, joseph gadzia, md3, larry dillon, md4, federico a. monzon, md2 1the university of tennessee health science center, memphis, tn; 2castle biosciences, inc., friendswood, tx; 3kansas medical clinic, topeka, ks; 4dr. larry dillon, colorado springs, co table 3. clinical and molecular features across treatment groups figure 3. schematic representation of risk stratification using ajcc stage with gep test result to guide patients’ clinical management clinical characteristics overalln=247 median age (range), years 63 (19-94) t stage t1 115 (47%) t2 66 (27%) t3 33 (13%) t4 18 (7%) not assessed 12 (6%) breslow thickness median (range), mm 1.1 (0.1-18.0) ≤1 mm 121 (49%) >1 mm 126 (51%) mitotic index <1/mm2 87 (35%) ≥1/mm2 160 (65%) ulceration absent 204 (83%) present 43 (17%) site trunk 77 (31%) extremity 124 (50%) head and neck 43 (17%) gep result class 1 181 (73%) class 2 66 (27%) feature dermatology n=74 surgical oncology n=166 medical oncology n=7 breslowa 0.6 (0.1-10.3) 1.3 (0.1-8.0) 1.1 (0.2-18.0) ulcerationb absent 65 (88%) 133 (80%) 6 (86%) present 9 (12%) 33 (20%) 1 (14%) mitosisb <1/mm2 38 (51%) 45 (27%) 4 (57%) ≥1/mm2 36 (49%) 121 (73%) 3 (43%) gep classb* class 1 60 (81%) 114 (69%) 7 (100%) class 2 14 (19%) 52 (31%) 0 (0%) amedian (range), bcount (percent), *p<0.05, fisher’s exact test study result berger (2016)4 prospective, multicenter n patients = 163 53% changed mgmt after inclusion of gep result farberg (2017)5 dermatologist survey n physicians = 169 47-50% changed mgmt after inclusion of gep result schuitevoerder (2017)6 prospective, single center n patients = 91 52% of mgmt decision based on gep result using decision tree model table 1. management changes in three clinical use studies class 2 decrease increase labs 3 22 imaging 4 41 visits 1 27 referral 3 13 figure 1. number of cases with a documented change in management class 2 n=66 total cohort n=247 class 1 n=181 slide number 1 skin january 2019 volume 3 issue 1 copyright 2018 the national society for cutaneous medicine 28 research letter rapid access clinic expedites patient connection with dermatologic services and improves productivity tn canavan, md1, rl pearlman, md1, be elewski, md1, lv graham, md, phd1 1department of dermatology, university of alabama at birmingham, birmingham, al access to dermatologic care, especially for urgent complaints, poses an ongoing challenge. to address long scheduling wait times and acute dermatologic complaints, institutions have sought innovative solutions to patient access problems.1-5 to improve access at the university of alabama at birmingham, a twice weekly rapid access clinic (rac) was implemented in 2017 where up to 60 patients are scheduled on tuesday. on fridays, 40 patients were scheduled for the first month with 50 scheduled the subsequent months. these clinics are staffed by 6 dermatology residents plus 2 attendings. referrals are not required. most appointments are scheduled within 2 weeks. this clinic has been in place for around one year and we continue to see a similar number of patients. visits are intended to be limited to a single dermatologic complaint, and patients are informed of this policy. a retrospective review was conducted for all rac patients seen over a 4-month period (9/1/2017-12/31/2017). twenty-seven clinics with 1018 visits were reviewed for demographics, diagnosis, and follow-up recommendations (table 1). the average patient age was 51.5 (range 5-100), 60.1% were female, and 89.7% were new patients. despite our intent to limit visits to 1 complaint, most patients had several complains addressed. seventy eight new cutaneous malignancies were diagnosed, including six melanomas (table 1). rac implementation reduced appointment wait times considerably. our department’s scheduling wait times before rac were 96 and 87 days for new and return patients, respectively (table 2). after 10 months of rac, the wait times were 35 and 32 days for table 1: characterizing patient population, patient diagnoses, and follow-up recommendations from rac. patient demographics (n=1018) mean (± sd) or n (%) age 51.5 (+/18.6) female gender 612 (60.1%) new patient 913 (89.7%) return patient with new complaint 49 (4.8%) total eruptions diagnosed 712 (47.9%) total neoplasms diagnosed 784 (52.1%) follow-up required 611 (60.0%) biopsy results number of patients (total number detected) bcc 39 (45) scc scc in situ 19 (23) 3 (3) melanoma 5 (6) adenocarcinoma 1 (1) skin january 2019 volume 3 issue 1 copyright 2018 the national society for cutaneous medicine 29 new, and returns. the no-show rate for rac was 17.3%. implementation of the biweekly rac model resulted in dramatic departmental productivity enhancement (table 2). the average rac encounter generated approximately 55% more wrvus on average than non-rac clinic visits due to a high proportion of new patients and procedures performed in rac vs non-rac clinic. by replacing one regular clinic with a rac, one faculty member noted an increase of over 1000 wrvus in a 5-month period. the change in wrvus could not be assessed for the other rac attending as they joined the department around the time rac was implemented. the most frequently used billing codes in rac were for skin biopsies, followed closely by destruction of benign lesions (table 2). rac significantly augmented our procedural referrals. rac resulted in 116 procedural referrals, including 54 distinct lesions referred for mohs surgery (table 2). table 2: identifying patient services and assessing productivity gains associated with rac. productivity measures metrics difference in rac vs non-rac wrvus (%) per encounter +55% change in wait times for new patients 61 days shorter change in wait times for return patients 55 days shorter no-show rate (% of rac appointments) 17.3% procedural referrals number of patients (total number of lesions to treat) excision 54 (58) mms 43 (54) laser treatment 4 (4) total 101 (116) table 2: continued. procedure code % of patients (n) skin biopsy (11100) 14.7 (150) destruction of benign lesions (17110) 12.3 (125) destruction of 1st premalignant lesion (17000) 10.2 (104) destruction of premalignant lesions 2-14 (17003) 7.0 (71) distinct procedural services (59 modifier) 4.6 (47) injection 1-7 lesions (11900) 2.2 (22) acne surgery (10040) 1.1 (11) implementing the rac model helped us achieve our goals of shortening wait times, enhancing department revenue, and diagnosing more cutaneous malignancies, especially melanomas. limitations of this study include its retrospective nature and short time frame. the rac was implemented at a large tertiary care academic center staffed by a sizeable department with a broad referral base, thus results may not be generalizable to all clinic settings. improving access to dermatologic care is complex; however, the rac model accomplishes this goal for patients with acute complaints. future studies are needed to assess the flexibility of implementing this model in different practice settings. conflict of interest disclosures: dr. elewski has been a consultant, in which she received honoraria, for the following companies: celgene, leo, lilly, novartis, pfizer, sun, and valeant. dr. elewski has received clinical research support (funds paid to the university of alabama at birmingham) from the following companies: abbvie, boehringer ingelheim, celgene, incyte, leo, lilly, merck, novartis, pfizer, regeneron, sun, and valeant. dr. graham has received clinical research support (funds paid to the university of alabama at birmingham) from pfizer and served as a consultant to ucb. the remaining authors have no conflicts of interest. funding: none. irb status: approved (irb-300000327) skin january 2019 volume 3 issue 1 copyright 2018 the national society for cutaneous medicine 30 corresponding author: lauren graham, md, phd department of dermatology university of alabama at birmingham birmingham, al lvgraham@uabmc.edu references: 1. suneja t, smith ed, chen gj, zipperstein kj, fleischer ab, feldman sr. waiting times to see a dermatologist are perceived as too long by dermatologists: implications for the dermatology workforce. arch dermatol 2001;137(10):1303–7. 2. tsang mw, resneck js. even patients with changing moles face long dermatology appointment wait-times: a study of simulated patient calls to dermatologists. j am acad dermatol 2006;55(1):54–8. 3. kimball ab, resneck js. the us dermatology workforce: a specialty remains in shortage. j am acad dermatol 2008;59(5):741–5. 4. murray m, berwick dm. advanced access: reducing waiting and delays in primary care. jama 2003;289(8):1035–40. 5. anderson be, marks jg, downs e, et al. the hershey access clinic: a model for improving patient access. j am acad dermatol 2007;57(4):601–3. mailto:lvgraham@uabmc.edu emmy graber,1 hilary baldwin,2 andrew f. alexis,3 james del rosso,4 richard g. fried,5 julie c. harper,6 adelaide hebert,7 leon kircik,8 evan a rieder,9 linda stein gold,10 siva narayanan,11 volker koscielny,12 ismail kasujee12 1the dermatology institute of boston and northeastern university, boston, ma; 2acne treatment and research center, brooklyn, ny; 3weill cornell medical college, new york, ny; 4jdr dermatology research/thomas dermatology, las vegas, nv; 5yardley dermatology associates, yardley, pa; 6the dermatology and skin care center of birmingham, birmingham, al; 7uthealth mcgovern medical school, houston, tx; 8icahn school of medicine, mount sinai, new york, ny; 9new york university grossman school of medicine, new york, ny; 10henry ford health system, bloomfield, mi; 11avant health llc, bethesda, md; 12almirall sa, barcelona, spain. objective: evaluate patient self-perceived av symptoms and impact of av on emotional/social functioning and adl, among av patients in community practices across the u.s. methods: single-arm, prospective cohort study (proses: nct04820673) was conducted with moderate-to-severe non-nodular av patients >9yrs who were prescribed sarecycline in real-world u.s community practices. validated asis questionnaire (with signs and impact (emotional & social) domains) and an expert panel questionnaire (epq; emotional functioning (items 1-4), social functioning (items 5-7), and adl (items 8-11)) were completed by patients (>12yrs) and caregivers (for patients 9-11yrs) at baseline and week-12. all items were scored on five-point adjectival response scale (score: 0 (never/not at all) – 4 (all the time/very much/extremely)); a higher asis domain score indicate severe symptoms or negative impact of av. asis domain scores and proportion of patients reporting score=2/3/4 (moderate to high burden/impact or parent understanding (epq10)) for epq items at baseline were analyzed. results: a total of 253 av patients completed the study (pediatric: 39.92%; female: 66.40%; moderate av: 86.56%; severe av: 13.44%). at baseline, patients reported moderate av burden in most domains, as depicted by the following domain score: signs: 1.96, impact: 2.06, emotional impact subdomain: 2.43; social impact subdomain: 0.98. from epq items, proportion of patients reporting score=2/3/4 (moderate to severe burden) at baseline were: patients’ mood/anger (epq1) – 56.13%; worries about av worsening (epq2) – 79.45%; thinking about acne (epq3) – 84.19%; level of acne worries (epq4) – 72.73; patients’ social media/’selfie’ activity (epq5) – 51.38%; impact on real-life plans (epq6) – 44.66%; efforts to hide av (epq7) – 72.73%; picked-on/judged due to av (epq8) – 26.88%; ability to reach future goals (epq9) – 27.27%; sleep impact (epq11) – 27.67%; parent understanding of av concerns (for patients<18yrs; epq10) – 84.16%. conclusion: moderate to severe av burden/impact was observed in this prospective cohort of av patients in the u.s. emotional impact and social impact of av were especially more pronounced among the av population. synopsis conclusions • moderate to severe av burden/impact was observed at study entry, in this prospective cohort of av patients in the u.s. emotional impact and social impact of av were especially more pronounced among the av population. methods • single-arm, prospective cohort study (proses: nct04820673) was conducted with moderate-to-severe non-nodular av patients ≥ 9yrs who were prescribed sarecycline in real-world u.s community practices. • a total of 300 subjects were enrolled from 30 community practices across the u.s. • validated asis questionnaire (with signs and impact (emotional & social) domains) and an expert panel questionnaire (epq; emotional functioning (items 1-4), social functioning (items 5-7), and adl (items 8-11)) were completed by patients (>12yrs) and caregivers (for patients 9-11yrs) at baseline and week-12. • asis items are scored on a five-point adjectival response scale (score 0-4); higher scores indicate severe symptoms or negative impact of acne. • epq items (1-9 & 11) were scored on five-point adjectival response scale (score: 0 (no burden/impact) – 4 (most burden/impact)); a higher epq score indicate severe symptoms or negative impact of av. • epq item 10 was scored on five-point adjectival response scale (score: 0 (not at all) – 4 (very much), this question only asked to the pediatric/caregiver subgroup; higher score indicate better understanding. • asis domain scores and proportion of patients reporting score=2/3/4 (moderate to high burden/impact) for individual epq items at baseline were evaluated, as observed. objective • evaluate patient self-perceived av symptoms and impact of av on emotional/social functioning and adl, among av patients in community practices across the u.s. majority of patients reported moderate to severe av burden in several areas associated with emotional and physical functioning, and adl note: n=253 *only asked for pediatric patient/caregiver subgroup (n=101). table 3: asis domain scores at baseline depicting moderate to severe av burden asis domain domain scores at baseline (n=253) signs 1.96 impact 2.06 emotional impact 2.43 social impact 0.98 results acne symptoms and impact of acne on social functioning, emotional functioning, and activities of daily living (adl) among patients with moderate to severe non-nodular acne vulgaris (av) in community practices across the u.s: an analysis of proses study cohort 56.13% 72.73% 79.45% 84.19% 43.87% 27.27% 20.55% 15.81% 0% 20% 40% 60% 80% 100% epq1: patients' mood/anger epq4: level of acne worries epq2: worries about av worsening epq3: thinking about acne p ro po rt io n of p at ie nt s reporting 0/1: never/ rarely reporting 0/1: not at all/ slightly reporting 2/3/4: some/ most/ all of the time reporting 2/3/4: somewhat/ moderately/ extremely epq domain: emotional functioning epq domain: social functioning epq domain: activities of daily living 51.38% 44.66% 72.73% 48.62% 55.34% 27.27% 0% 20% 40% 60% 80% 100% epq5: patients’ social media/’selfie’ activity epq6: impact on real-life plans epq7: efforts to hide av p ro po rt io n of p at ie nt s reporting 0/1: never/ rarely reporting 2/3/4: some/ most/ all of the time 26.88% 27.67% 27.27% 84.16% 73.12% 72.33% 72.73% 20.55% 0% 20% 40% 60% 80% 100% epq8: picked-on/judged due to av epq11: sleep impact epq9: ability to reach future goals epq10*: parent understanding of av concerns p ro po rt io n of p at ie nt s reporting 0/1: never/ rarely reporting 2/3/4: some/most/all of the time ■ reporting 0/1: not at all/ a little ■ reporting 2/3/4: somewhat/ quite a bit / very much ■ reporting 0/1: not at all/ slightly ■ reporting 2/3/4: somewhat/ moderately/ extremely table 1: baseline patient characteristics n=253 age group, % pediatric (<18 yrs) 39.92 adult (≥18 yrs) 60.08 age group, mean pediatric (<18 yrs) 14.81 adult (≥18 yrs) 26.63 gender, % male 33.60 female 66.40 race,% white 66.80 other 15.81 black/african american 9.88 asian 5.93 prefer not to answer 3.16 american indian or alaskan 0.79 native hawaiian/pacific islander 0.40 ethnicity,% (hispanic, latino or of spanish origin) yes 33.99 no 66.01 baseline iga, % moderate 86.56 severe 13.44 table 2: site characteristics n=30 current workplace, % private, office-based practice 100.00 hospital-based practice 0.00 total number of board-certified dermatologists in the clinic/practice, mean 3.10 number of patients with av managed by the clinic in a given month, mean 86.90 number of years practicing dermatology, mean 19.30 skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 170 brief article cutaneous type pemphigus vulgaris of the scalp: a rare unilesional presentation stefanie altmann, do1, adam chahine, md1, jarett casale, do2, jessica forbes, bs3, sarah ferrer-bruker, do1,4 1orange park medical center, orange park, fl 2sampson regional medical center, clinton, nc 3nova southeastern university college of osteopathic medicine, davie, fl 4park avenue dermatology, orange park, fl pemphigus represents a rare group of autoimmune bullous diseases affecting the skin and mucous membranes with an incidence of 1 to 16 per million annually.1,2 pemphigus vulgaris (pv) is the most common subtype, comprising 70% of all cases of pemphigus and can be further subdivided into mucocutaneous and mucosal dominant types, depending on the extent of cutaneous involvement.1 almost all cases of pv have mucosal involvement; however, a rare variant of cutaneous-only pv has been reported in the literature.3 we present a case of cutaneous-only pv involving the scalp. a 36-year-old otherwise healthy caucasian woman presented to the dermatology office with a painful, pruritic, erythematous plaque isolated to the vertex scalp that had been present for one year. the patient had previously seen an outside provider and was prescribed a four-week oral prednisone taper, oral minocycline, ketoconazole shampoo, and gentamicin ointment. minimal improvement was noted on this regimen, and the patient was still experiencing pain and irritation which led her to seek secondary evaluation by a dermatology physician. physical examination at this time revealed a beefy red, macerated plaque on her vertex scalp with overlying scale (figure 1). no other cutaneous or mucosal lesions were noted. two 4-mm punch biopsies were performed and sent for histopathological and immunohistochemical analysis. laboratory studies included cbc, cmp, quantiferontb gold, a hepatitis panel, and an hiv test. histopathology revealed suprabasilar acantholytic dermatitis at all levels of the epidermis (figure 2). direct abstract pemphigus vulgaris (pv) is the most common subtype of pemphigus, a rare group of autoimmune bullous diseases affecting the skin and mucous membranes. pv can be further subdivided into mucocutaneous and mucosal dominant types, depending on the extent of cutaneous involvement. almost all cases of pv have mucosal involvement; however, a rare variant of cutaneous-only pv has been reported in the literature. to our knowledge, only two previous accounts of unilesional scalp pv have been reported. we present an unusual case of cutaneous-only pv involving the scalp. introduction case presentation skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 171 immunofluorescence staining was positive for linear/granular igg deposition throughout the epithelial cell surfaces. linear/granular deposits of c3 were also noted in the lower two-thirds of the epithelial strata (figures 3, figure 4). no immunoreactants were noted at the basement membrane zone and no iga, igm, c5b-9 or fibrinogen deposits were seen. these immunofindings, coupled with the histological analysis, strongly supported the diagnosis of pemphigus vulgaris. figure 1. initial presentation—beefy, red, macerated plaque on the vertex scalp. the patient was treated with mycophenolate mofetil 500mg twice daily, prednisone 20mg twice daily, doxycycline 100mg twice daily, and fluocinolone oil. one-month follow-up revealed significant improvement of the scalp lesion. the patient was maintained on mycophenolate mofetil 500mg twice daily with topical fluocinonide oil and prednisone was tapered off. at six-month follow-up she had nearly complete resolution. serum indirect immunofluorescence was assessed after nine months of treatment and was nonreactive on monkey esophagus, salt-split skin, and murine bladder correlating with successful disease remission and clinical clearance. figure 2. histopathology showing suprabasilar acantholysis and characteristic “tombstoning” of basilar keratinocytes (h&e, 10x). pv is an autoimmune bullous disease that can affect both the skin and mucous membranes. autoantibodies to desmoglein (dsg) antigens represent the major pathogenic factor in pemphigus. mucosal dominant pv has predominantly anti-dsg3 autoantibodies, while mucocutaneous pv has both anti-dsg3 and anti-dsg1 autoantibodies. cutaneous-type pv (cpv) is an extremely rare variant of pv that presents with cutaneous findings in the absence of any mucosal involvement. currently, there is limited literature on this mucosal-sparing phenotype with only a handful of documented cases.3,4,5 rangel reported one case of cutaneous-type pv associated with pregnancy.4 gheisari et al. recently reported that 30/560 (5.3%) of their studied patients with pv had only cutaneous involvement, suggesting that cpv is much more prevalent than previously thought.5 furthermore, only two previous accounts of unilesional scalp pv have been reported.6,7 our case is a unique presentation of unilesional cutaneous pv in a young woman. discussion skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 172 figure 3. direct immunofluorescence showing igg deposition involving follicular epithelium of the scalp. (igg, 400x) figure 4. direct immunofluorescence showing linear/granular deposits of igg throughout the epidermis of the scalp. (igg, 400x) scalp involvement is seen in 16-60% of patients with pv and is the primary location in 9-15% of patients.8 the high frequency of scalp involvement in pv is likely due to the presence of high levels of desmogleins in hair follicles.8 in cases of suspected pemphigus limited to the scalp, the additional use of trichoscopy can aid in diagnosis.7 several hypotheses for the pathogenesis of cpv have been proposed in the literature. yoshida et al. hypothesized cpv to be caused by a combination of pathogenically weak anti-dsg3 with potent anti-dsg1.3 sarpomian et al. suggested that other antigens may be involved as targets in the pathogenesis of pv and that the desmoglein autoantibodies detected may be the result, rather than the cause, of the observed acantholysis.8 carew et al. reported concomitant pathogenic and non-pathogenic epitopes of dsg3 in mice.2 further studies are needed to fully understand this complex pathogenesis. in our case, elisa was not performed in addition to iif, but could be a consideration in future cases to help potentially understand the pathogenesis of cpv. the clinical significance of this case highlights a rare form of pv without mucosal involvement, a hallmark of pv. it is important to consider pemphigus vulgaris, even in the absence of mucosal involvement when evaluating isolated scalp lesions. abbreviations: pv – pemphigus vulgaris pf – pemphigus foliaceous gerd – gastroesophageal reflux disease dsg – desmoglein dif – direct immunofluorescence conflict of interest disclosures: this research was supported in part by hca healthcare or an hca healthcare affiliated entity. the views expressed in this publication represent those of the authors and do not necessarily represent the official views of hca healthcare or any of its affiliated entities. funding: none corresponding author: stefanie altmann, do division of dermatology orange park medical center 2001 kingsley ave orange park, fl 32073 phone: 401-414-6556 conclusion skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 173 email: stefanie.altmann@hcahealthcare.com references: 1. kridin k. pemphigus group: overview, epidemiology, mortality, and comorbidities. immunol res. 2018;66(2):255-270. 2. carew b, wagner g. cutaneous pemphigus vulgaris with absence of desmoglein 1 autoantibodies. an example of the extended desmoglein compensation theory. australas j dermatol. 2014;55(4):292-295. 3. yoshida k, takae y, saito h, et al. cutaneous type pemphigus vulgaris: a rare clinical phenotype of pemphigus. j am acad dermatol. 2005;52(5):839-845. 4. rangel j. pregnancy-associated "cutaneous type" pemphigus vulgaris. perm j. 2016;20(1):e101–2. 5. gheisari m, shahidi-dadrass m, nasiri s, dargah sm, dadkhahfar s, abdollahimajd f. cutaneoustype of pemphigus vulgaris. j am acad dermatol. 2020;83(3):919-920. 6. oretti g, giordano d, di lella f, gradoni p, zendri e, ferri t. unilesional pemphigus vulgaris of the scalp after cochlear implantation. am j otolaryngol. 2011 jan-feb;32(1):80-1. 7. ferrara g, massone c, zalaudek i, argenziano g. unilesional pemphigus vulgaris of the scalp. dermatol online j. 2009 oct 15;15(10):9. 8. sar-pomian m, rudnicka l, olszewska m. the significance of scalp involvement in pemphigus: a literature review. biomed res int. 2018;2018:1-8. mailto:stefanie.altmann@hcahealthcare.com skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 19 research letters perceptions of teledermatology among people with hidradenitis suppurativa ashley eichelberger, crnp1, melissa butt, mph1, colleen silva, md1, aretha mosley1, joslyn s. kirby, md, ms, med1 1department of dermatology, penn state milton s hershey medical center, hershey, pa coronavirus disease (covid-19) impacted healthcare delivery for providers and patients as encounters shifted from inperson to telehealth. teledermatology has become widespread during this time. its benefits include reduced wait times and improved access, which support its ongoing use.1,2 teledermatology can be valuable for people with hidradenitis suppurativa (hs) who may require maintenance therapy, as well as flare interventions, for the chronic and acute aspects of this inflammatory skin disease, respectively.3 however, we hypothesized people with hs may have concerns or challenges participating in teledermatology due to the location of hs lesions in body areas that are sensitive or difficult to photograph without assistance. the objective of this survey study was to investigate patients’ perceived challenges and willingness-to-pay for teledermatology as compared to in-person visits for hs management. a cross-sectional survey was conducted march 23 – may 1, 2020. the survey was developed and data managed in redcap, a secure web-based software.4 the survey was developed by the authors and pilot tested prior to dissemination. a link to an abstract introduction: hidradenitis suppurativa (hs) is a chronic inflammatory condition that requires frequent dermatology visits. coronavirus disease (covid-19) led to a shift in healthcare delivery to telemedicine. teledermatology can be valuable for hs patients to decrease travel and wait times and improve patient access. however, we hypothesized that people with hs may have concerns or challenges participating in hs due to its frequent occurrence in sensitive or difficult-to-photograph locations. methods: a cross-sectional survey was sent to patients with hs at one academic institution as well as leaders of three patient networks. results: survey responses were received from 149 patients. a total of 94.4% were willing to have an online appointment due to covid-19, and 88.9% were willing to use teledermatology if covid-19 had not happened. 32.3% of patients reported that they had ever missed an appointment not due to covid-19. discussion: our findings support patient willingness to use teledermatology for treatment and management of their hs. introduction methods skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 20 anonymous survey was sent to people with hs seen at one academic institution and to leaders of three patient networks. in addition, network recruitment was utilized, as participants could share the link with family and friends with hs. data analysis, including descriptive statistics and chi square for comparisons, was conducted in may 2020 using sas 9.4. the study was reviewed and approved by the penn state institutional review board. a total of 149 patients completed the survey (table 1). the actual response rate is unknown since it cannot be determined what number received the link. survey results (table 2) indicate that 140 (94.6%) patients were willing to have an online appointment due to covid-19. additionally, 132 (89.2%) patients identified they would be willing to use teledermatology if covid-19 had not happened. patient-reported concerns with teledermatology were: concern with provider difficulty in assessing hs (74 patients, 50.0%), and concern with the security of their photos (64 patients, 43.2%) or the security of their information (46 patients, 31.1%). in total, 38 (26.5%) respondents missed or cancelled an appointment because of covid-19. additionally, 46 (32.3%) patients identified that they have ever missed or cancelled an appointment for reasons other than covid-19. the survey provided possible options for missing appointments other than covid-19 and the most common responses included: 17 (37.0%) patients who identified that they were not able to leave work/school/duties at home, as well as 17 (37.0%) patients who identified that they were feeling really low/depressed and did not feel like attending their appointment. table 1. participant characteristics (n=149) variable n (%) sex male 12 (8.1) female 136 (91.2) decline to answer 1 (0.7) age (1 missing) 18-24 13 (8.8) 25-34 37 (25.0) 35-44 52 (35.1) 45-54 31 (21.0) 55-64 12 (8.1) 65+ 3 (2.0) ethnicity hispanic/latino 8 (5.3) non-hispanic/latino 137 (92.0) decline to answer 4 (2.7) race asian 5 (3.4) black/ aa 11 (7.4) american indian/ alaska native 2 (1.3) white 119 (79.9) mixed race 7 (4.7) decline to answer 5 (3.4) our findings support shah et al. and their emphasis on the utilization and effectiveness of teledermatology to diagnose, treat, and manage patients with hs.3 the results of this study are useful for clinicians so that they can anticipate some of the teledermatology-related concerns or challenges for people with hs. patient concerns included cost of the teledermatology appointments, security of their photos and information during these visits, and the ability for the provider to adequately assess their hs through these visits. privacy and accuracy concerns could be addressed by sharing information about the software’s security features and demonstrated accuracy of teledermatology5, respectively. regarding cost, telehealth has been covered by insurance during the results discussion skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 21 table 2. n (%) yes p value have you missed an in-person appointment for your hs or cancel close to the date: due to covid? unrelated to covid? 38 (25.5) 46 (30.9) 0.32 most frequent reasons for missed in-person appointment: work, school, duties at home feeling low/depressed too much hs-related pain 17/46 (37.0) 17/46 (37.0) 16/46 (34.8) are you willing to have an online appointment with your dermatologist? due to covid? unrelated to covid? 140 (94.6) 132 (89.2) 0.09 are you willing to submit photos of your hs to your doctor through the computer? due to covid? unrelated to covid? 140 (94.6) 137 (92.6) 0.48 most frequent concerns about teledermatology: provider difficulty assessing hs security of my photos security of my information 74 (50.0) 64 (43.2) 46 (31.1) covid-19 pandemic and there is pressure to continue this coverage.6 there are limitations to this study. the results may not be generalizable due to recall bias or selection bias related to online recruitment. this was a cross-sectional study so cannot determine changes in telehealth use over time or clinical outcomes. overall, teledermatology was welcomed by our patients and will hopefully be used during this challenging time and thereafter. irb status: the study was reviewed and approved by the penn state institutional review board conflict of interest disclosures: kirby: speaker for abbvie, consultant for abbvie, chemocentryx, incyte, novartis, ucb eichelberger, silva, butt, mosley: no disclosures funding: none corresponding author: joslyn s. kirby, md, ms, med associate professor penn state milton s hershey medical center 500 university dr hershey, pa 17033 email: jkirby1@pennstatehealth.psu.edu references: 1. gupta r, ibraheim mk, doan hq. teledermatology in the wake of covid-19: advantages and challenges to continued care in a time of disarray. j am acad dermatol. 2020. 2. latifi r, doarn cr. perspective on covid-19: finally, telemedicine at center stage. telemed j e health. 2020. 3. shah m, naik hb, alhusayen r. hidradenitis suppurativa: the importance of virtual outpatient care during covid-19 pandemic. j am acad dermatol. 2020. 4. harris pa, taylor r, thielke r, payne j, gonzalez n, conde jg. research electronic data capture (redcap)--a metadata-driven methodology and workflow process for providing translational research informatics support. j biomed inform. 2009;42(2):377381. 5. lamel s, chambers cj, ratnarathorn m, armstrong aw. impact of live interactive teledermatology on diagnosis, disease management, and clinical outcomes. arch dermatol. 2012;148(1):61–65. 6. wicklund, e., 2020. experts weigh in on post-covid19 telehealth rules and policies. [online] mhealthintelligence. available at: <https://mhealthintelligence.com/news/experts-weighin-on-post-covid-19-telehealth-rules-and-policies> [accessed 17 june 2020]. skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 338 brief articles new-onset vitiligo following etanercept for ankylosing spondylitis carly dunn, ba1, stacy l. mcmurray, md1, allison jones, md1, debendra pattanaik, md2 1department of dermatology, university of tennessee, memphis, tn 2division of rheumatology, university of tennessee, memphis, tn tumor necrosis factor-alpha (tnf-α) inhibitors are used widely to treat a variety of chronic inflammatory conditions such as ankylosing spondylitis (as), crohn’s disease, rheumatoid arthritis, and psoriasis. although tnf-α inhibitors have been proven to be effective and safe for use in many conditions, reports of paradoxical immunological skin conditions, such as psoriasis, granuloma annulare, lichen planus, and vitiligo, are associated with their use.1,2,3 we report a case of as who initiated therapy with a tnf-α inhibitor and developed vitiligo shortly thereafter. a 19-year-old male with diagnosis of as was referred by rheumatology for evaluation of suspected vitiligo. the patient was initially treated for as with adalimumab which failed to control the disease. he was subsequently switched to etanercept with marked improvement in his as symptoms. however, within a month of starting etanercept, he developed depigmented macules and patches on his upper vermillion lip (figure 1), anterior base of the neck, dorsal hands (figure 2), volar wrists, and thighs. the patient had no personal or family history of vitiligo. despite the marked improvement in as symptoms, the decision was made per abstract tumor necrosis factor-alpha (tnf-α) inhibitors, are used widely to treat a variety of chronic inflammatory conditions such as ankylosing spondylitis, crohn’s disease, rheumatoid arthritis, and psoriasis. recently, there has been an increase in the number of reports of immunemediated skin diseases, such as lichen planus, psoriasis, or granuloma annulare, following the initiation of tnf-α inhibitors. although the exact mechanism is unknown, the proposed hypothesis is that tnf-α blockade results in a cytokine shift which activates autoreactive t cells and ultimately leads to an immunologic imbalance. we present a patient with ankylosing spondylitis previously treated with adalimumab who developed vitiligo shortly after switching to etanercept to achieve better control of his joint disease. there is no currently treatment algorithm for new-onset vitiligo following tnf-α inhibitor use. in many cases the drug is continued with a favorable outcome; however, withdrawal of the tnf-α inhibitor with initiation of an alternative tnf-α agent or biologic agent in a different class may be considered. introduction case report skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 339 patient and physicians to switch from etanercept to secukinumab due to the vitiligo. at his 3-month follow up the patient’s skin lesions were stable with no progression of disease. figure 1. depigmented patch on patient’s upper vermillion lip. figure 2. well-circumscribed depigmented macules and patches on patient’s dorsal hands. tnf-α has been linked to the pathogenesis of vitiligo. this cytokine has been shown to inhibit melanocyte differentiation and function and can cause apoptosis of melanocytes.4 simon et al showed that tnfα blockade can improve existing vitiligo.5 however, there have been an increasing number of reports of new-onset vitiligo following initiation of tnf-α inhibitors. since the first case report of de novo vitiligo under infliximab in 2005,6 there have been at least 17 other case reports as well as a retrospective study and a population-based study detailing cases from use of various biological agents.1,3,7,8,9 one study estimates one per 5437 patients on a biologic agent will develop de novo vitiligo.9 although the exact mechanism is unknown, it is postulated that tnf-α inhibition modifies the cytokine balance and affects downstream pathways, resulting in activation of autoreactive t cells and immunologic imbalance.4,7 a retrospective study by exarchou et al showed that 10 out of 183 (5.5%) patients with as who had been treated with tnf-α inhibitors had immune-mediated skin lesions (with one case of vitiligo).1 a 10-year population-based study demonstrated an increased risk of vitiligo in patients receiving tnf-α inhibitors, with an incidence rate of 5.9 vs 2.5 per 10,000 person-years in those on tnf-α inhibitors versus control, respectively. this translates to an overall increased risk of 1.99 in the treatment group. in subgroup analysis, they found that the risk of vitiligo was highest in female patients, those on etanercept, and patients with as.7 our patient adds to the growing number of reports of etanercept-induced vitiligo in as after prior treatment failure with adalimumab. as de novo vitiligo following tnf-α inhibitor use is rare, there is currently no treatment algorithm for this phenomenon. in a nationwide retrospective study by merybossard et al, 18 patients with de novo vitiligo were reported from july 2013 to january 2015.8 in most cases (66.6%) the drug was continued without any worsening of the vitiligo. however, in six of these cases discussion skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 340 patients underwent treatment with topical steroids, which may be a confounding factor. in three cases, the tnf-α inhibitor was changed, due to the underlying inflammatory condition, without progression of the patients’ vitiligo. the authors conclude that continuing anti-tnf-α therapy is appropriate if the underlying inflammatory condition is well-controlled. other therapy options include an alternative tnf-α inhibitor or another biological agent in patients whose underlying inflammatory condition had not improved or whose skin lesions progress.8 with growing literature describing immunemediated skin diseases following tnf-α inhibitors, dermatologists, rheumatologists, and gastroenterologists need to be aware of these potential side-effects. an interdisciplinary approach to a patient presenting with vitiligo following initiation of a tnf-α inhibitor can help determine whether the patient should continue the tnf-α inhibitor, switch to a different tnf-α inhibitor, or start an alternative biologic medication. conflict of interest disclosures: none funding: none corresponding author: carly dunn, ba department of dermatology, university of tennessee 1977 butler blvd, suite e6.200 houston, tx 77030 713-870-5413 carly.dunn@gmail.com references: 1. exarchou sa, voulgari dv, markatseli te, zioga a, drosos aa. immune-mediated skin lesions in patients treated with anti-tumor necrosis factor alpha inhibitors. scand j rheum. 2009;38(5):328-331. 2. ismail wa, al-enzy sa, alsurayei sa, ismail ae. vitiligo in a patient receiving infliximab for refractory ulcerative colitis. arab j gastroenterol. 2011;12(2):109-111. doi:10.1016/j.ajg.2011.03.001. 3. carvalho cldb, ortigosa lcm. segmental vitiligo after infliximab use for rheumatoid arthritis – a case report. an bras dermatol. 2014;89(1). doi: 10.1590/abd1806-4841.20142887 4. toussirot e, aubin f. paradoxical reactions under tnf-α blocking agents and other biological agents given for chronic immune-mediated diseases: an analytical and comprehensive overview. rmd open. 2016;2(2):1-12. doi:10.1136/rmdopen-2015-000239. 5. simon ja, burgos-vargas r. vitiligo improvement in a patient with ankylosing spondylitis treated with infliximab. case rep dermatol. 2008;216:234-235. doi: 10.1159/000112932 6. ramirez‐hernandez m, marras c, martinez‐ escribano ja. infliximab‐induced vitiligo. dermatology 2005; 210(1):79–80. doi:10.1159/000081494. 7. bae jm, kim m, lee hh, et al. increased risk of vitiligo following anti-tumor necrosis factor therapy: a 10-year population-based cohort study. j invest dermatol. 2018;138(4):768-774. doi:10.1016/j.jid.2017.11.012. 8. mery-bossard l, bagny k, charby g, et al. new onset vitiligo and progression of pre-existing vitiligo during treatment with biological agents in chronic inflammatory diseases. j eur acad dermatol venerol. 2017;31:181-186. doi:10.1111/jdv.13759. 9. webb kc, tung r, winterfield ls, et al. tumour necrosis factor-α inhibition can stabilize disease in progressive vitiligo. br j dermatol. 2015;173(3):641–650. doi:10.1111/bjd.14016. mailto:carly.dunn@gmail.com https://doi.org/10.1159/000112932 skin may 2018 volume 2 issue 3 copyright 2018 the national society for cutaneous medicine 181 brief articles coexisting basal cell carcinoma and squamous cell carcinoma in congenital nevus sebaceous jordan rosen bs a , katherine nolan md a , noah shaikh bs a , les rosen md a , martin zaiac md a a department of dermatology and cutaneous surgery, university of miami miller school of medicine, miami, fl nevus sebaceous (ns) is a congenital epidermal hamartoma that is present in less than 1% of newborns. 1 ns appears classically on the face or scalp as a waxy, yellowor orange-colored linear or round plaque. lesions can involve the epidermis, hair follicle, sebaceous glands, and apocrine glands. ns frequently increases in size during puberty. 2 as patients age, there is an increasing risk for the development of cutaneous neoplasms within ns. 3 the vast majority of ns-associated neoplasms are benign. malignant neoplasms, most notably basal cell carcinoma (bcc), represent less than 1% of the cutaneous neoplasms arising from ns, and frequently affect those over the age of twenty. 3,4 we report the fourth case to our knowledge of bcc and scc arising concurrently in the same ns. a 56-year-old hispanic female with no significant medical history presented to clinic regarding a lesion on her left cheek (figure 1). the lesion had been present since birth but had begun to grow over the last several months. the patient also noted mild discomfort at the site of the lesion beginning around the same time that the lesion started to grow. family history was negative for any skin cancers or other malignancies. on examination there was a well-defined 1.4-cm x 0.8-cm pink, translucent, pearly ovoid plaque with arborizing telangiectasias overlying the mandible on the left cheek. two biopsies were taken from the lesion edges and were sent for pathological examination. the first biopsy specimen abstract nevus sebaceous is a congenital epidermal hamartoma characterized by hyperplastic changes to the epidermis and adnexa. nevus sebaceous is associated with an elevated risk of cutaneous neoplasms, most often benign; however, malignant neoplasms, most notably basal cell carcinoma, can also present in these patients. although a rare occurrence more often affecting adult patients, squamous cell carcinomas have also been reported to arise at the site of pre-existing nevus sebaceous. herein we report a unique case of a patient with basal cell carcinoma and squamous cell carcinoma arising concurrently in the same nevus sebaceous. introduction case report skin may 2018 volume 2 issue 3 copyright 2018 the national society for cutaneous medicine 182 revealed acantholysis, papillamotosis, dilated apocrine glands, large sebaceous lobules, and a lack of terminal hairs, all of which are consistent with ns (figures 2-3). the second biopsy demonstrated nodular basaloid tumor nests, with a peripheral palisading pattern, fibromyxoid stroma, and focal retraction. additionally, the second biopsy showed a prominent surrounding inflammatory infiltrate with eosinophils and peripheral trapping of elastic fibers. the findings in the second biopsy were congruent with a superficial type bcc in association with a scc (figures 4-5). given the location of the lesion and the malignant features, the patient underwent mohs surgery for complete removal of the ns. pathological evaluation of the surgical specimen confirmed clear margins. at 6-month follow-up the surgical site is now well healed with no evidence of reoccurrence. figure 1. a 1.4x0.8cm pink, translucent, pearly, ovoid papule with arborizing telangiectasias involving the left cheek figure 2. classic features of nevus sebaceous are seen, including papillomatosis and acanthosis. (a) h&e 5x (b) h&e 10x (c) h&e 20x skin may 2018 volume 2 issue 3 copyright 2018 the national society for cutaneous medicine 183 figure 3. apocrine glands and large sebaceous lobules are present throughout the dermis (h&e 20x) figure 4. within the nevus sebaceous there are characteristic findings of bcc with nodular basaloid tumor nests, peripheral palisading, fibromyxoid stroma and focal retraction artifact (a) h&e 5x (b) h&e 10x figure 5. there is scc characterized by proliferation of atypical keratinocytes with glassy cytoplasm extending into the reticular dermis in association with an inflammatory cell infiltrate consisting of eosinophils, lymphocytes, and histocytes (a) h&e 5x (b) h&e 20x a. b. a. b. skin may 2018 volume 2 issue 3 copyright 2018 the national society for cutaneous medicine 184 although ns is considered a benign congenital lesion, there are important associations and considerations to take when caring for such patients. ns is classically thought to progress through three clinical stages as patients age. the first stage occurs throughout childhood and presents with a smooth yellowor orangecolored plaque characterized by limited hair or sebaceous glands. the second stage, occurring during puberty and likely related to hormonal changes, is associated with a more verrucous appearing lesion and maturation of apocrine and sebaceous glands. finally, the last stage is associated with the presence of benign and malignant cutaneous neoplasms. 5 ambiguity regarding ns and the risk of future malignancy has made it difficult for physicians to determine when to recommend surgical excision versus continued observation with follow-up. ns are often found on the scalp and, unsurprisingly, tumors arising from within ns occur more frequently on the scalp. 6 the most common tumor types that are found to arise within ns are benign; more specifically, between 90% and 97.5% of tumors developing within ns are benign. 2,3 trichoblastoma and syringocystadenoma are the most common neoplasms that occur in ns. 2,3 the most common malignant tumor associated with ns is bcc, followed by scc. 2 the mean age of patients presenting with bcc or scc is 54 and 49 years of age, respectively. 2 additionally, there have been three similar cases of bcc and scc arising concurrently within an ns. unlike this case, which describes a lesion on the mandible, the other three cases describe lesions in other areas. the earliest case was described in 1970 in a 56-year-old woman who presented with an ulcerated lesion on the temple. 7 in 2005, ball et al. reported a case of bcc and scc developing from within an ns located on the scalp of a 35-year-old man. 8 lastly, in 2007, arshad et al. described a similar case of a 55-year-old man with scc and bcc arising from a ns on the scalp 9 ; despite wide excision and radiotherapy, the patient’s scc metastasized, leading the author to suspect increased aggression of scc that arises from within ns. 9 while, in this case report we describe an extremely rare case of simultaneous bcc and scc in a single lesion of nevus sebaceous, there have been other reports of two distinct malignancies developing in the background of ns. 10 there have been two reported cases of simultaneous sccs developing within a single ns. 10,11 although uncommon for children to develop scc within ns, belhadjali et al. reported a case of an 11-year-old patient with ns containing two simultaneous sccs in different stages of invasion. 11 in that case the lesion was excised and was not reported to have reoccurred. in conclusion, this case describes the rare occurrence of simultaneous bcc and scc in a single lesion of ns. while basaloid and adnexal neoplasms are most commonly thought of in relation to ns, this case highlights that scc can also occur and be associated with more aggressive behavior. the association between bcc, scc, and ns may also offer insight into the underlying pathogenesis of these three neoplasms. discussion skin may 2018 volume 2 issue 3 copyright 2018 the national society for cutaneous medicine 185 conflict of interest disclosures: none funding: none corresponding author: jordan rosen, bs university of miami miller school of medicine 1600 nw 10 th ave miami, fl 33136 305-781-5342 (office) j.rosen14@med.miami.edu references: 1. alper jc, holmes lb. the incidence and significance of birthmarks in a cohort of 4,641 newborns. pediatr dermatol. 1983;1(1):58-68. 2. idriss mh, elston dm. secondary neoplasms associated with nevus sebaceus of jadassohn: a study of 707 cases. j am acad dermatol. 2014;70(2):332-37. 3. cribier b, scrivener y, grosshans e. tumors arising in nevus sebaceus: a study of 596 cases. j am acad dermatol. 2000;42(2):263-68. 4. jaqueti, g., requena, l. and yus, e. (2000). trichoblastoma is the most common neoplasm developed in nevus sebaceus of jadassohn. am j dermatopathol. 22(2), pp.108-118. 5. eisen db, michael dj. sebaceous lesions and their associated syndromes: part i. j am acad dermatol. 2009;61(4):549-60. 6. rosen h, schmidt b, lam hp, meara jg, labow bi. management of nevus sebaceous and the risk of basal cell carcinoma: an 18‐year review. pediatr dermatol. 2009;26(6):676-81. 7. wilson-jones e. naevus sebaceus. a report of 140 cases with special regard to the development of secondary malignant tumours. br j dermatol. 1970;82:99-117. 8. ball, e., hussain, m. and moss, a. (2005). squamous cell carcinoma and basal cell carcinoma arising in a naevus sebaceous of jadassohn: case report and literature review. clinical and experimental dermatology. 30(3), pp.259-260. 9. arshad, a., azman, w. and kreetharan, a. (2008). solitary sebaceous nevus of jadassohn complicated by squamous cell carcinoma and basal cell carcinoma. head & neck. 30(4), pp.544-548. 10. turan e, buyukgural b, ilhan celik o. simultaneous occurrence of two squamous cell carcinomas developing in a nevus sebaceous. arch iranian med. 2015;18(4):253-6. 11. belhadjali h, moussa a, yahia s, njim l, zakhama a, zili j. simultaneous occurrence of two squamous cell carcinomas within a nevus sebaceous of jadassohn in an 11‐year‐old girl. pediatr dermatol. 2009;26(2):236-37. skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 817 brief article treatment of severe recalcitrant atopic dermatitis with dupilumab in a kidney transplant patient vivian li, mms1, sophie guenin, msc2 3, mark lebwohl, md3 1lake erie college of osteopathic medicine, erie, pa 2new york medical college, valhalla, ny 3department of dermatology, icahn school of medicine at mount sinai, new york, ny atopic dermatitis (ad) is a chronic inflammatory skin condition that affects both children and adults. clinical symptoms of ad include severe itching, redness, and dry skin. ad relapse is driven by genetic predisposition and includes altered skin barrier function associated with filaggrin gene mutation and filaggrin deficiency.1 type 2 cytokines such as interleukin (il)-4 and il-13 play a significant role in the pathogenesis of ad. il-4 has been shown to initiate the th2 response while il-13 maintains the response.1 although topical corticosteroids are the first line treatment for ad, systemic immunomodulating agents such as mycophenolate mofetil or prednisone may be used in patients who do not respond well to topical therapy or have severe refractory ad.2 these systemic agents aim to reduce cutaneous inflammation and achieve longterm disease control by disrupting disease pathways, leading to reduced lymphocyte proliferation; however, these treatments are related to notable adverse effects, such as an increased risk of infections and the occurrence of rebound flares.3,4 this case report highlights the unique specificity and safety of dupilumab, a biologic agent that selectively targets cytokines (il-4 and il-13) that are crucial in the pathogenesis of ad, in abstract this case report highlights the successful treatment of refractory atopic dermatitis (ad) in an immunosuppressed patient using dupilumab, a biologic agent that selectively targets cytokines crucial in the pathogenesis of ad. the patient had a history of failed treatment with numerous topical and systemic immunomodulating agents, including corticosteroids and immunosuppressive drugs for organ transplant. dupilumab treatment resulted in significant improvement of symptoms, including reduced pruritus, and ultimately achieved disease control. importantly, the patient experienced no adverse effects apart from one covid-19 infection over three years of co-administration of dupilumab with immunosuppressive transplant rejection treatment. the safety of dupilumab in immunocompromised and transplant patients has been a concern, but studies have shown its safety and efficacy in these patient populations. this case highlights the potential for dupilumab as a safe and effective treatment option for patients with severe ad who are immunocompromised or have undergone solid organ transplantation. introduction skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 818 successfully treating an immunosuppressed patient with refractory ad. a 30-year-old male first presented to us with severe atopic dermatitis in the context of an atopic triad. his past medical history included congenital kidney dysplasia and end-stage renal disease for which he received three kidney transplantations. of note, he was on oral tacrolimus 1.5 mg twice daily, mycophenolate mofetil 1000 mg twice daily, and prednisone 5 mg daily for transplant immunosuppression. his atopic dermatitis was inadequately controlled with fluocinonide cream and clobetasol, evidenced by the presence of pigmented patches, xerosis, excoriations, and mild to moderate, generalized pruritus throughout the body. over the next year, the patient was treated with phototherapy and various topicals, such as pimecrolimus, tacrolimus, mometasone, and methylprednisolone. notably, his oral transplant anti-rejection medications did not adequately treat his ad symptoms. the following year, the patient presented with exacerbation of his ad, asthma, and allergies. at this time, his eczema assessment severity index (easi) score was 37 and he was initiated on dupilumab therapy. the dupilumab treatment consisted of an initial 600 mg dose, followed by 300 mg dose every two weeks thereafter. within two weeks of his initial treatment, the patient reported that his skin had improved considerably, and the general level of pruritus had reduced significantly. physical examination during the patient’s follow-up appointment three months later showed that his skin was clear, and the symptoms of ad had largely disappeared. his use of topical treatments for ad is minimal, with rare flares controlled with topical ruxolitinib. the patient’s easi score was reduced to 0, and he reports a dramatic increase in quality of life. importantly, the patient experienced no adverse effects apart from one covid-19 infection over three years of co-administration of dupilumab with immunosuppressive transplant rejection treatment. dupilumab is a monoclonal antibody that selectively inhibits the signaling of both il-4 and il-13, key drivers of the inflammatory response in atopic dermatitis, by binding to their shared receptor alpha subunit.5 this blocks downstream signaling and ultimately decreases the th2-driven inflammatory response to help reduce skin inflammation and improve skin barrier function.5 dupilumab is approved for the treatment of moderate to severe atopic dermatitis.5 patients in the dupilumab clinical trials reported 75% or greater improvement from their baseline easi score over the course of sixteen weeks, relief from pruritus, and enhanced quality of life.5 although our patient was on an immunosuppressive organ transplant regimen, his ad remained uncontrolled. mycophenolate mofetil inhibits the proliferation of t and b cells thereby, reducing the production of cytokines that contribute to inflammatory pathways.6 similarly, oral tacrolimus functions by forming a complex with fkbp-12 to inhibit the downstream effects of calcineurin, a key enzyme responsible for t-cell activation.7 prednisone, a corticosteroid, broadly suppresses the immune system.8 however, despite a robust combination of immunosuppressive therapies, our patient’s ad failed to respond. case report discussion skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 819 the safety of dupilumab in immunocompromised and transplant patients has been a concern due to the potential risk of infections and impaired immune function. however, lukac et al. conducted a study which demonstrated the safety of dupilumab in these patient populations.9 other studies have also reported successful use of dupilumab in patients with ad and underlying primary immunodeficiency disorders, such as x-linked agammaglobulinemia and hyper ige syndrome.10,11 the risk of infections with dupilumab appears to be similar to that of placebo, and there have been no reports of opportunistic infections or reactivation of latent infections.12 demonstrated by our patient, dupilumab can be considered as a safe and effective treatment option for patients with severe ad who are immunocompromised or have undergone solid organ transplantation. conflict of interest disclosures: vivian li and sophie guenin have no conflicts of interest. mark lebwohl is an employee of mount sinai and receives research funds from: abbvie, amgen, arcutis, avotres, boehringer ingelheim, cara therapeutics, dermavant sciences, eli lilly, incyte, inozyme, janssen research & development, llc, novartis, ortho dermatologics, regeneron, and ucb, inc. dr. lebwohl is also a consultant for anaptysbio, arcutis, inc., arena pharmaceuticals, aristea therapeutics, avotres therapeutics, biomx, boehringer-ingelheim, brickell biotech, castle biosciences, corevitas, dermavant sciences, evommune, inc., facilitatation of international dermatology education, forte biosciences, foundation for research and education in dermatology, hexima ltd., meiji seika pharma, mindera, national society of cutaneous medicine, new york college of podiatric medicine, pfizer, seanergy, sun pharma, verrica, and vial. funding: none corresponding author: vivian li, mms lake erie college of osteopathic medicine erie, pa email: livivian23@gmail.com references: 1. dubin c, del duca e, guttman-yassky e. the il4, il-13 and il-31 pathways in atopic dermatitis. expert rev clin immunol. 2021;17(8):835-852. doi:10.1080/1744666x.2021.1940962 2. sidbury r, davis dm, cohen de, et al. guidelines of care for the management of atopic dermatitis: section 3. management and treatment with phototherapy and systemic agents. j am acad dermatol. 2014;71(2):327-349. doi:10.1016/j.jaad.2014.03.030 3. sidbury r, kodama s. atopic dermatitis guidelines: diagnosis, systemic therapy, and adjunctive care. clin dermatol. 2018;36(5):648652. doi:10.1016/j.clindermatol.2018.05.008 4. davari dr, nieman el, mcshane db, morrell ds. current perspectives on the systemic management of atopic dermatitis. j asthma allergy. 2021;14:595-607. published 2021 jun 1. doi:10.2147/jaa.s287638 5. simpson el, bieber t, guttman-yassky e, et al. two phase 3 trials of dupilumab versus placebo in atopic dermatitis. n engl j med. 2016;375(24):2335-2348. doi:10.1056/nejmoa1610020 6. eichenfield lf, tom wl, berger tg, et al. guidelines of care for the management of atopic dermatitis: section 2. management and treatment of atopic dermatitis with topical therapies. j am acad dermatol. 2014;71(1):116-132. doi:10.1016/j.jaad.2014.03.023 7. cross sa, perry cm. tacrolimus once-daily formulation: in the prophylaxis of transplant rejection in renal or liver allograft recipients. drugs. 2007;67(13):1931-1943. doi:10.2165/00003495-200767130-00012 8. siegels d, heratizadeh a, abraham s, et al. systemic treatments in the management of atopic dermatitis: a systematic review and metaanalysis. allergy. 2021;76(4):1053-1076. doi:10.1111/all.14631 9. lukac d, pagani k, mcgee js. overview of use, efficacy, and safety of dupilumab in complex patients: a retrospective, case-series study from a large, urban academic center [published online ahead of print, 2022 jun 18]. arch dermatol res. 2022;10.1007/s00403-022-02362-y. doi:10.1007/s00403-022-02362-y 10. fan yh, lin tl, sun hl, pan hh, ku ms, lue kh. successful treatment of atopic dermatitis with dupilumab in the setting of x-linked agammaglobulinemia. j allergy clin immunol pract. 2022;10(11):3032-3034.e1. doi:10.1016/j.jaip.2022.07.026 skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 820 11. wang hj, yang tt, lan ce. dupilumab treatment of eczema in a child with stat3 hyperimmunoglobulin e syndrome. j eur acad dermatol venereol. 2022;36(5):e367-e369. doi:10.1111/jdv.17889 12. blauvelt a, de bruin-weller m, gooderham m, et al. long-term management of moderate-tosevere atopic dermatitis with dupilumab and concomitant topical corticosteroids (liberty ad chronos): a 1-year, randomised, doubleblinded, placebo-controlled, phase 3 trial. lancet. 2017;389(10086):2287-2303. doi:10.1016/s0140-6736(17)31191-1 brodalumab, a human anti–interleukin-17 receptor a monoclonal antibody, shows low immunogenicity in patients with moderate-to-severe psoriasis kristian reich,1 mark lebwohl,2 carle paul,3 mads røpke,4 monika rosen,4 klaus hansen4 1dermatologikum hamburg and sciderm research institute, hamburg, germany; 2icahn school of medicine at mount sinai, new york, ny, usa; 3paul sabatier university, toulouse, france; 4leo pharma, ballerup, denmark winter clinical dermatology conference hawaii® • january 12-17, 2018 • lahaina, hi introduction • brodalumab is a human anti–interleukin (il)-17 receptor a monoclonal antibody, which is delivered via subcutaneous injection, that demonstrated high efficacy in the treatment of moderate-to-severe psoriasis1–4 • biologic therapies, such as brodalumab, have the potential to elicit an immune response in humans, which may result in the production of anti-drug antibodies (adas)5 • adas may change the pharmacokinetic and/or pharmacodynamic profile of a drug and thereby compromise its efficacy and/or safety profile6 – adas have been associated with hypersensitivity and immune reactions,7,8 which may be preceded by localized inflammation at an injection site9,10 – neutralizing antibodies can prevent the drug from binding to the target receptor11 • this analysis was performed to evaluate immunogenicity and rates of hypersensitivity and injection-site reactions related to brodalumab methods study design • immunogenicity data from a 12-week phase ii study (nct00975637),1 its open-label extension (nct01101100; cut-off date: 16 june 2014),2 and three 52-week phase iii studies (amagine-1,3 -2 and -34) were included • all studies were placebo controlled for the first 12 weeks, and amagine-2 and -3 also included ustekinumab as a comparator up to week 52 – treatment changes were incorporated into the design of each study; therefore, patients had exposure to different therapies and experienced different durations of treatment with those therapies – brodalumab was administered at doses of 70, 140 or 210 mg every 2 weeks (q2w), with an additional initial dose at week 1, or at a dose of 280 mg every 4 weeks (q4w) immunogenicity assessments • in the phase ii study, serum samples were tested at baseline and weeks 4 and 16 • in the phase ii open-label extension, serum samples were tested at the open-label extension baseline and weeks 4, 12, 24, 36, 48 and every 24 weeks thereafter (to a maximum of week 336 or end of treatment) • in the phase iii studies, serum samples were tested at baseline and weeks 0, 4, 12, 24, 48 and 52 • samples were treated with 300 mm acetic acid to enable antibody complex dissociation prior to analysis and thus increase the probability that anti-brodalumab antibodies would be detected • a highly sensitive (15 ng/ml) electrochemiluminescent bridging immunoassay with a drug tolerance threshold of 100.0 μg/ml, defined by a positive-control antibody, was used to detect brodalumab-specific adas in samples • samples with a positive immunoassay result were tested for brodalumab-specific neutralizing adas with a validated cell-based assay that used il-8 cytokine measurement as a surrogate endpoint – assay sensitivity was 0.5 μg/ml, with a lower limit of reliable detection of 2.5 μg/ml and a drug tolerance of 0.78–1.25 μg/ml – confirmatory assays were conducted on positive samples by incubating the sample in the absence of il-17 and brodalumab statistical analysis • this analysis included all patients who received at least one dose of brodalumab in any of the studies • adas were considered to be transient if the result of the patients’ final on-study test was negative • descriptive statistics were used to summarize positive and negative antibody responses in each treatment group results patients • immunogenicity was assessed in a total of 4461 patients across all studies – 564 patients were treated with ustekinumab before they received brodalumab 210 mg anti-drug antibodies • steady-state brodalumab serum concentrations were below the drug tolerance threshold in all samples for the immunoassay used to detect adas • 122 patients (2.7%) tested positive for adas at any time after receiving brodalumab (table 1) – 15 patients also tested positive for adas at baseline – adas were transient in 58 patients (1.4%) • no patients had neutralizing adas, including those who received brodalumab 210 mg after ustekinumab (table 1) effect of anti-drug antibodies pharmacokinetics • because anti-brodalumab antibody incidence was <3% of the patient population, anti-brodalumab antibody status was not evaluated in a population pharmacokinetic model; however, based on tabulated pharmacokinetic data (data not shown), no trends were observed to suggest reduction in pharmacokinetics due to the presence of binding adas efficacy • there was no clear initial indication that patients with adas developed tolerance to brodalumab with loss of therapeutic effect, based on static physician’s global assessment (spga) responses. among patients with binding adas: – 3/5 (60%) patients treated with brodalumab 210 mg q2w and 9/14 (64%) patients treated with brodalumab 140 mg q2w achieved spga success (score of 0 or 1) at week 12 – 7/14 (50%) patients in the brodalumab 210 mg q2w group, 1/12 (8.3%) in the 140 mg q8w group, 0/8 in the 140 mg q4w group, and 5/21 (24%) in the 140 mg q2w group achieved spga success at week 52 hypersensitivity and injection-site reactions • no meaningful differences were observed in the incidence of hypersensitivity or injection-site reactions for brodalumab compared with placebo or ustekinumab within the 12 weeks of the phase ii study or the 12-week induction phases of the phase iii studies (table 2) – the most frequent (≥0.3% in any group) hypersensitivity reaction was pruritus – the most frequent injection-site reactions were injection-site pain, erythema, bruising, and generalized injection-site reaction • there were no reports of serious hypersensitivity or injection-site reactions in the first 12 weeks of the study, including hypersensitivity within 1 day of treatment administration table 1. total antibody incidence brodalumab 140 mg q2w* (n=279) brodalumab 210 mg q2w† (n=1291) variable brodalumab dosing‡ (n=2327) brodalumab 210 mg after ustekinumab§ (n=564) all (n=4461) patients with a positive ada result prior to the first dose of brodalumab n=255 n=1257 n=2231 n=562 n=4305 binding 0 4 (0.3) 4 (0.2) 7 (1.2) 15 (0.3) neutralizing 0 0 0 0 0 patients with an on-study positive ada result n=277 n=1287 n=2325 n=564 n=4453 binding 6 (2.2) 24 (1.9) 78 (3.4) 14 (2.5) 122 (2.7) neutralizing 0 0 0 0 0 patients with a positive ada result after the first active brodalumab dose who had a negative or no result before the first active brodalumab dose n=274 n=1281 n=2316 n=375 n=4246 binding 6 (2.2)0 20 (1.6) 74 (3.2) 7 (1.9) 107 (2.5) transient 3 (1.1) 8 (0.6) 44 (1.9) 3 (0.8) 58 (1.4) neutralizing 0 0 0 0 0 transient 0 0 0 0 0 all data are n (%) unless otherwise stated. treatment groups are as treated after the first dose of brodalumab. *≥75% of doses were 140 mg. †≥75% of doses were 210 mg. ‡all other brodalumab-treated patients without ustekinumab exposure. §includes three patients not randomized to ustekinumab who inadvertently received a dose of ustekinumab. table 2. incidence of hypersensitivity and injection-site reactions up to week 12 placebo (n=879) ustekinumab (n=613) brodalumab 140 mg q2w (n=1491) brodalumab 210 mg q2w (n=1496) all brodalumab doses* (n=3066) hypersensitivity aes† 27 (3.1) 8 (1.3) 39 (2.6) 26 (1.7) 66 (2.2) pruritus 14 (1.6) 5 (0.8) 18 (1.2) 10 (0.7) 28 (0.9) injection-site reaction‡ 11 (1.3) 12 (2.0) 25 (1.7) 23 (1.5) 56 (1.8) injection-site pain 3 (0.3) 4 (0.7) 7 (0.5) 9 (0.6) 20 (0.7) injection-site erythema 3 (0.3) 3 (0.5) 6 (0.4) 5 (0.3) 16 (0.5) injection-site bruising 2 (0.2) 1 (0.2) 4 (0.3) 4 (0.3) 9 (0.3) injection-site reaction 0 (0.0) 1 (0.2) 5 (0.3) 1 (0.1) 4 (0.1) all data are n (%). *70 mg q2w (n=38), 140 mg q2w (n=1491), 210 mg q2w (n=1496), 280 mg q4w (n=41). †standardized medical dictionary for regulatory activities (meddra) query. ‡amgen-defined medical query. acknowledgments: the brodalumab clinical study programme was sponsored by amgen/ astrazeneca, and this analysis was performed by amgen/astrazeneca. this poster was sponsored by leo pharma. medical writing support was provided by laura maguire, mchem from mudskipper business ltd, funded by leo pharma. author disclosures: the authors disclose past or current financial relationships with the following companies: reich – abbvie, affibody, amgen, biogen, boehringer ingelheim, celgene, centocor, covagen, forward pharma, glaxosmithkline, janssen-cilag, leo pharma, lilly, medac, merck, novartis, ocean pharma, pfizer, regeneron, sanofi, takeda, ucb, and xenoport; lebwohl – amgen, anacor, boehringer ingelheim, celgene, eli lilly, janssen biotech, kadmon, leo pharma, medimmune, novartis, pfizer, sun pharmaceutical industries, and valeant pharmaceuticals north america llc; paul – none; røpke – leo pharma; rosen – leo pharma; and hansen – leo pharma. references: 1. papp ka et al. n engl j med. 2012;366:1181-1189. 2. papp ka et al. j am acad dermatol. 2014;71:1183-1190. 3. papp ka et al. br j dermatol. 2016;175:273-286. 4. lebwohl m et al. n engl j med. 2015;373:1318-1328. 5. purcell rt & lockey rf. j invest allergol clin immunol. 2008;18:335-342. 6. smith a et al. j immunol res. 2016;2016:2342187. 7. schellekens h. clin ther. 2002;24:1720-1740. 8. lecluse lla et al. arch dermatol. 2010;146:127-132. 9. liang f & loré k. clin transl immunology. 2016;5:e74. 10. martinon f et al. annu rev immunol. 2009;27:229-265. 11. van schouwenburg pa et al. j biol chem. 2014;289:34482-34488. conclusions • the overall incidence of brodalumab-specific immunogenicity in patients with moderateto-severe psoriasis was low, and adas were transient in almost half the patients in whom they were detected • brodalumab-neutralizing adas were not detected in any patients, including those who received brodalumab 210 mg after ustekinumab • there was no association between adas and reduction of response to brodalumab or increased incidence of hypersensitivity or injection-site reactions © 2017. all rights reserved. powerpoint presentation patient preferences for vehicle and overall preference of calcipotriene 0.005%/betamethasone dipropionate 0.064% foam and gel in the pso-insightful study chih-ho hong, md1, dharm s. patel, phd2, katja wendicke lophaven, msc2 1university of british columbia, department of dermatology and skin science and probity medical research, 2leo pharma introduction results conclusions materials & methods acknowledgements references  topical therapies are the first-line treatment for mild-tomoderate plaque psoriasis or are used in combination with other therapies for severe disease.1  patient compliance to topical therapy is a significant issue, with adherence rates estimated at 40-70%.2 patient preference for vehicle formulation can impact adherence, and thus, real-life effectiveness.3  the pso-insightful study was designed to gain insight on patient reported factors that influence preference following once-daily topical treatment with calcipotriene 0.005%/betamethasone dipropionate 0.064% foam and gel.  subjects’ preference assessment (spa) and vehicle preference measure (vpm) were completed by patients to assess preference differences based on vehicle and overall preference of cal/bd foam and gel. pso-insightful study design  pso-insightful was a prospective, multicenter, phase iiib, open-label, randomized, two-arm crossover study held in germany and canada (nct02310646)4  adult patients ≥ 18 years with mild-to-severe psoriasis of ≥ 6 months’ involving 2-30% body surface area (bsa) and mpasi ≥ 2 were included in study (table 1)  after a 4-week washout period, 213 patients were randomized 1:1 to once-daily cal/bd foam for 1 week, followed by cal/bd gel for 1 week, or vice-versa (fig 1) figure 1: schematic of study design of pso-insightful, [nct02310646]4 study assessments  patients completed questionnaires to assess therapy usability and preference differences: o subjects’ preference assessment (spa) – developed by leo pharma o vehicle preference measure (vpm) – wake forest health sciences5 all patients n = 212 (%) age category, n (%) 18 – 39 years 48 (22.6) 40 – 59 years 92 (43.4) ≥ 60 years 72 (34.0) male : female, n (%) 133:79 (63:37) bmi, n (%) < 25 kg/m2 37 (17.5) 25 – 30 kg/m2 73 (34.4) > 30 kg/m2 102 (48.1) pga, n (%) mild 61 (28.8) moderate 122 (57.5) severe 29 (13.7) duration of psoriasis, n (%) < 2 years 4 (1.9) 2 – 5 years 30 (14.2) > 5 years 178 (84.0) bsa, n (%) < 4% 93 (43.9) 4 – 6% 56 (26.4) 6 – 11% 38 (17.9) 11 – 15% 11 (5.2) ≥ 15% 14 (6.6) mpasi, n (%) 2 – 5 86 (40.6) 5.1 – 10 91 (42.9) > 10 35 (16.5) mean dlqi 7.8 localized:widespread distribution of psoriasis, % 62:38 table 1. patient demographics and baseline characteristics (adapted from pso-insightful) bmi, body mass index; bsa, body surface area; mpasi, modified psoriasis and severity index; pga, physician’s global assessment of disease severity  spa: individual baseline characteristics were examined in a two-factor logistic regression model including treatment sequence and various baseline characteristics as factors.  the full analysis set (fas) comprised all randomized patients who completed an on-study questionnaire. statistical analysis subjects’ preference assessment (spa)  at the end of week 2 visit, patients completed: o spa: comprised of two domains, the patient indicated: (a) if they preferred cal/bd foam or gel based on the previous 14 days; and (b) how much each of the 22 application-, formulation and container-related items contributed to their overall preference using a four-point scale ranging from ‘very important’ to ‘not at all important’ vehicle preference measure (vpm)  at the end of weeks 1 and 2, patients completed questionnaire based on their treatment experience during the previous 7 days: o vpm: comprised seven items that were assessed on a seven-point scale ranging from –3, ‘extremely unappealing’, to +3, ‘extremely appealing’  the pso-insightful study demonstrated that overall patient preference was similar between cal/bd foam and gel.  main drivers for patients preferring cal/bd foam over gel were items related to sensation (i.e. ‘immediate feeling of relief’ and ‘felt soothing to skin’)  cal/bd gel scored higher vs foam for items related to ease of application, time it takes to apply, and odor.  cal/bd foam was generally preferred by younger patients (aged 18–39 years), whereas cal/bd gel tended to be preferred by older patients (aged ≥40 years).  pso-insightful study demonstrates that psoriasis patients have diverse needs and different preferences for topical treatment, which can influence adherence and outcomes. figure 2: reasons for preference of cal/bd foam (spa): (a) application; (b) formulation; and (c) container items (fas). subjects’ preference assessment (spa)  equal preference of subjects preferring foam and the other half gel (table 2)  logistic regression analysis performed to identify baseline characteristics driving preference choices: o a difference in preference between age category was observed (table 2) o no robust findings on other baseline characteristics (e.g. gender, disease severity, phenotype)  reason for preference not very discriminant, however: o for foam, size of application area and items related to feeling of relief/soothing seems to be a preference factor (fig 2) o for gel, precision of application seems to be preference factor (fig 3) figure 3: reasons for preference of cal/bd gel (spa): (a) application; (b) formulation; (c) container items (fas). poster presented at the 2018 winter clinical dermatology conference in maui, hi; january 12-17th, 2018. table 3. vehicle preference measure (vpm) for cal/bd foam and gel. generally high scores for both cal/bd foam and gel (table 3): • the highest mean scores for foam for: o ‘time it takes to apply’ o ‘how it feels on the skin’ • the highest mean scores for gel for o ‘time it takes to apply’ o ‘ease of application’ o ‘how it smells’ • no major difference between treatments (significant for odor) 1. nast, a. et al. european s3-guidelines on the systemic treatment of psoriasis vulgaris-update 2015--short version--edf in cooperation with eadv and ipc. j. eur. acad. dermatol. venereol. jeadv 29, 2277–2294 (2015). 2. devaux, s. et al. adherence to topical treatment in psoriasis: a systematic literature review. j. eur. acad. dermatol. venereol. 26, 61–67 (2012). 3. feldman, s. r. et al. psoriasis: improving adherence to topical therapy. j. am. acad. dermatol. 59, 1009–1016 (2008). 4. nct02310646 patient insights following use of leo 90100 aerosol foam and daivobet® gel in subjects with psoriasis vulgaris. available at: http://www.clinicaltrial.co/showtrial/nct02310646. (accessed: 3rd november 2017) 5. housman, t. s., mellen, b. g., rapp, s. r., fleischer, a. b. & feldman, s. r. patients with psoriasis prefer solution and foam vehicles: a quantitative assessment of vehicle preference. cutis 70, 327–332 (2002). this study was sponsored by leo pharma. up to 14 days, if needed cal/bd foam cal/bd foam 7 days 7 days visit 2 day 8 visit 1 day 1 screening day -28 to 1 visit 3 day 15 cross-overrandomization 4-week washout, if needed follow-up cal/bd gel cal/bd gel vpm 1 vpm 2 spa assessment: 51 46 48 50 45 46 49 47 53 32 35 31 37 34 39 30 26 31 0 20 40 60 80 100 quickly absorbed dried quickly immediate feeling of relief felt soothing appleaing to touch felt moisturising not too greasy odorless absence of staining 52 55 43 54 32 31 33 34 0 20 40 60 80 100 out of container easy easy to use easy to keep clean desired amount (a) (b) (c) 51 50 39 47 34 41 44 38 54 39 39 41 39 39 44 38 41 36 0 20 40 60 80 100 quickly absorbed dried quickly immediate feeling of relief felt soothing appleaing to touch felt moisturising not too greasy odorless absence of staining 52 57 45 59 41 36 38 33 0 20 40 60 80 100 out of container easy easy to use easy to keep clean desired amount (a) (b) (c) 54 61 52 46 50 44 46 49 56 37 30 41 45 38 42 46 42 36 0 20 40 60 80 100 ease of application ease of application on lesion only ease of spreading lack of mess good for small areas good for large areas quick to apply total time spent acceptable easily incorporated into daily routine very important (gel pref.) fairly important (gel pref.) 51 48 65 48 54 62 55 57 61 30 31 24 34 30 26 34 26 24 0 20 40 60 80 100 ease of application ease of application on lesion only ease of spreading lack of mess good for small areas good for large areas quick to apply total time spent acceptable easily incorporated into daily routine very important (foam pref.) fairly important (foam pref.) age class prefer foam prefer gel all (n=208) 49.5% 50.5% 18-39 years (n=48) 72.9% 27.1% 40-59 years (n=90) 44.4% 55.6% >=60 years (n=70) 40.0% 60.0% table 2. overall patient preferences, by age, for cal/bd foam or gel. foam mean (n=211) gel mean (n=210) ease of application 1.5 1.9 time it takes to apply 1.9 2.0 how well it is absorbed 1.4 1.4 how it feels to touch 1.4 1.6 how it smells 1.6 1.9 how it feels on the skin 1.8 1.8 how much it stains 1.4 1.3 slide number 1 scan qr code to download this poster. background • psoriasis (pso) is a chronic, inflammatory disease that affects the skin, with an estimated prevalence of 2.6% to 3.7% in the united states1 • pso is associated with many comorbidities, including psoriatic arthritis (psa)2; up to 30% of patients with pso may have a concurrent diagnosis of psa3,4 • secukinumab is a fully human, interleukin-17a inhibitor approved for treatment of both psa and pso; it has demonstrated significant efficacy in moderate to severe plaque pso, improvement of physical functioning and quality of life, resolution of enthesitis and dactylitis, and inhibits progression of joint structural damage5-9 • little is known about treatment satisfaction and symptom control with secukinumab among patients with psa and pso in a real-world setting objective • to evaluate patient-reported secukinumab treatment satisfaction and psa symptom control in us patients with pso in conjunction with psa in a real-world setting methods study design and patient population • data were collected from a cross-sectional, panel-based web survey of patients with psa in the united states – a random sample of patients were invited to participate in the survey by survey sampling international through their patient panels – of 2755 patients screened for psa or ankylosing spondylitis (as), 269 patients with psa were eligible for the analysis • eligible patients were ≥ 18 years of age with a self-reported diagnosis of psa, initiated secukinumab ≥ 3 months before survey participation, and had received secukinumab continuously since initiation – of the 269 eligible patients with psa, 266 completed the survey; 66 patients had concurrent as and were not included in this analysis, and 3 did not consent to participate – patients included in this analysis also had a self-reported diagnosis of pso in conjunction with active psa study variables and data analysis • patient characteristics, including demographics, clinical characteristics, and medication history, were assessed at the time of survey participation • the primary outcomes were satisfaction with secukinumab treatment and with psa symptom control, including joint pain or tenderness, pain disrupting sleep, swelling of entire finger or toe, fatigue, morning stiffness, ankle and heel pain, and sore areas other than joints • descriptive analyses were conducted for each question; data were summarized using frequency counts and percentages for categorical variables and mean and standard deviation for continuous variables results patient population • of eligible patients with psa who completed the survey; 56 patients (28.0%) with concurrent pso were included in this analysis – demographics and patient characteristics are shown in table 1 • most patients (89.3%) received ≥ 1 biologic prior to secukinumab treatment (table 1) us patient satisfaction with secukinumab treatment among patients with both psoriatic arthritis and psoriasis: data from a web-based survey marina magrey, md,1 daniel wolin, bs,2 margaret mordin, ms,2 lori mcleod, phd,2 eric davenport, mecon, mstat,2 peter hur, pharmd, mba3 1case western reserve university, cleveland, oh; 2rti-health solutions, research triangle park, nc; 3novartis pharmaceuticals corporation, east hanover, nj your document will be available for download at the following url: http://http://novartis.medicalcongressposters.com/default.aspx?doc=305c7 and via text message (sms) text: q305c7 to: 8nova (86682) us only +18324604729 north, central and south americas; caribbean; china +447860024038 uk, europe & russia +46737494608 sweden, europe note: downloading data may incur costs which can vary depending on your service provider and may be high if you are using your smartphone abroad. please check your phone tariff or contact your service provider for more details. presented at the 2018 winter clinical dermatology conference; january 12-17, 2018; lahaina, hi. table 1. patient demographics and clinical characteristics characteristics patients with psa and pso(n = 56) age, mean (sd) 35.7 (10.6) male, n (%) 33 (58.9) race*, n (%) white 46 (82.1) hispanic 21 (37.5) black 5 (8.9) other 4 (7.1) region, n (%) east 10 (17.9) south 17 (30.4) midwest 19 (33.9) west 10 (17.9) years since psa symptom onset, mean (sd) 4.4 (4.6) years since diagnosis with psa, mean (sd) 3.6 (4.1) deformities due to psa, n (%) 45 (80.4) comorbidity*, n (%) anxiety 33 (58.9) depression 26 (46.4) obesity 22 (39.3) fatigue 21 (37.5) prior biologic use, n (%) biologic experienced 50 (89.3) biologic naive 6 (10.7) biologic use prior to secukinumab, n (%) adalimumab 32 (57.1) certolizumab pegol 21 (37.5) etanercept 31 (55.4) golimumab 18 (32.1) infliximab 19 (33.9) rituximab 19 (33.9) ustekinumab 12 (21.4) ixekizumab 18 (32.1) psa, psoriatic arthritis; pso, psoriasis. * patient may select all that apply. discontinuation of prior treatments • lack of efficacy (27.3%) was the most frequently cited reason for the discontinuation of previous treatment (figure 1) psa symptoms before and after secukinumab initiation • 85.7% of patients reported better overall symptom control after secukinumab initiation compared with before secukinumab initiation (“a little better,” 26.8%; “moderately better,” 39.3%; “much better,” 19.6%) (figure 2) – better symptom control was noted for each psa symptom assessed in the online survey (figure 2) time to symptom improvement after secukinumab initiation • of the patients who reported overall psa symptom improvement after secukinumab initiation (n = 48), the majority (n = 30; 62.5%) noticed overall symptom improvement within 4 weeks of initiating secukinumab; ≈ 90% of patients experienced improvement within 6 months (figure 3) • ≥ 50% of patients experienced a fast improvement (within 2 weeks) in joint pain and fatigue figure 3. patient-reported time to first noticeable improvements in psa disease symptoms since secukinumab initiation 40.6 16.1 43.6 51.4 34.2 27.0 50.0 16.7 34.4 64.5 35.9 20.0 44.7 48.6 23.8 45.8 15.6 9.7 12.8 20.0 13.2 13.5 19.0 22.9 3.1 6.5 5.1 5.7 5.3 5.4 4.8 10.4 6.2 3.2 2.6 2.9 2.6 5.4 2.4 4.2 0 10 20 30 40 50 60 70 80 90 100 ankle or heel pain† sore areas other than joints morning stiffness fatigue swelling of entire finger/toe* pain disrupting sleep joint pain or tenderness overall current psa symptoms proportion of patients, % within 2 weeks 3-4 weeks 1-2 months 3-6 months > 6 months * an indicator of dactylitis. † an indicator of enthesitis. treatment satisfaction with secukinumab • the majority of patients with pso in conjunction with psa expressed overall satisfaction (“very satisfied” and “mostly satisfied”) with their secukinumab treatment experience (figure 4) • most patients also reported better treatment experience with secukinumab compared with their previous treatment (figure 5) – > 90% of patients experienced better overall symptom improvement compared to their previous treatment figure 4. overall treatment satisfaction with secukinumab (n = 56) 64.3 33.9 55.4 58.9 55.4 41.1 71.4 26.8 57.1 32.1 26.8 30.4 53.6 21.4 7.1 7.1 12.5 14.3 14.3 5.4 7.1 1.8 1.8 0 10 20 30 40 50 60 70 80 90 100 patient support services side effects ease of use method of administration frequency of treatment speed of symptom improvement symptom improvement proportion of patients, % very satisfied mostly satisfied somewhat satisfied not satisfied figure 5. treatment experience with secukinumab compared with previous treatment (n = 56) 72.7 58.2 54.5 67.3 63.6 58.2 56.4 90.9 25.5 38.2 40.0 30.9 36.4 38.2 43.6 9.1 1.8 3.6 5.5 1.8 3.6 0 10 20 30 40 50 60 70 80 90 100 ease of switching to secukinumab patient support services side effects ease of use method of administration frequency of medication speed of symptom improvement overall symptom improvement proportion of patients, % secukinumab better about the same previous treatment better limitations • the patient population in this analysis was small (n = 56) • as with all survey-based research, patient perspectives may be subject to the patients’ bias and experience • this is a cross-sectional study which may be influenced by recall bias conclusions • in this real-world analysis, > 60% of patients with pso in conjunction with psa experienced overall symptom improvement within 4 weeks of initiating secukinumab • the majority of patients were satisfied with secukinumab treatment and reported better treatment experience with secukinumab than with their previous treatment • these results provide early insight into secukinumab treatment satisfaction among us patients with pso in conjunction with psa references 1. rachakonda td, et al. j am acad dermatol. 2014;70(3):512-6. 2. greb je, et al. nat rev dis primers. 2016;2:16082. 3. reich k, et al. br j dermatol. 2009;160(5):1040-7. 4. mease pj, et al. j am acad dermatol. 2013;69(5):729-35. 5. langley rg, et al. n engl j med. 2014;371(4):326-38. 6. mease pj, et al. n engl j med. 2015;373(14):1329-39. 7. mcinnes ib, et al. lancet. 2015;386(9999):1137-46. 8. kavanaugh a, et al. arthritis care res (hoboken). 2017;69(3):347-55. 9. husted ja, et al. arthritis care res (hoboken). 2011;63(12):1729-35. disclosures m. magrey received research funding from abbvie for clinical trials; served as a consultant for janssen and novartis; and was a member of an advisory board for janssen, novartis, and ucb. d. wolin, m. mordin, l. mcleod, and e. davenport are employees of rti-health solutions. p. hur is an employee of novartis. acknowledgments support for third-party writing assistance for this poster, furnished by kheng bekdache, phd, of health interactions, inc, was provided by novartis pharmaceuticals corporation, east hanover, nj. this study was sponsored by novartis pharmaceuticals corporation, east hanover, nj. © 2017 novartis pharmaceuticals corporation. figure 1. reasons for discontinuation of previous treatment prior to secukinumab treatment (n = 55) 1.8 3.6 3.6 5.5 7.3 10.9 16.4 23.6 27.3 too many doctor visits decline of insurance coverage high frequency of dosing high co-pay inconvenient treatment regimen painful injection/infusion fear of injections/needles side effects lack of efficacy 0 10 20 30 40 50 proportion of patients, % figure 2. improvement in psa symptoms with secukinumab compared with before secukinumab initiation * an indicator of dactylitis. † an indicator of enthesitis. 0 0 5.8 6.7 0 2.2 9.1 1.8 5.3 4.8 1.9 2.2 6.1 10.9 0 7.1 0 7.1 5.8 6.7 8.2 0 3.8 0 10.5 14.3 11.5 6.7 8.2 6.5 7.5 5.4 18.4 14.3 21.2 15.6 12.2 23.9 22.6 26.8 36.8 40.5 15.4 24.4 38.8 39.1 20.8 39.3 28.9 19.0 38.5 37.8 26.5 17.4 35.8 19.6 0 10 20 30 40 50 60 70 80 90 100 ankle or heel pain† sore areas other than joints morning stiffness fatigue swelling of entire finger/toe* pain disrupting sleep joint pain or tenderness overall proportion of patients, % a lot worse moderately worse a little worse no change a little better moderately better much better skin may 2018 volume 2 issue 3 copyright 2018 the national society for cutaneous medicine 175 brief articles development of bullous pemphigoid while receiving pd-1 checkpoint inhibitor nivolumab zp nahmias md a , ed merrill b , cc briscoe jd a , ce mount md c , s abner md a , a schaffer md phd a , mj anadkat md a a washington university school of medicine, st. louis, mo b university of missouri-kansas city school of medicine, kansas city, mo c allegheny general dermatology, pittsburgh, pa monoclonal antibodies (mab) targeting components of cell cycle regulation are a proven modality for the treatment of cancer. blockade of the programmed death-1 (pd-1) pathway provides a treatment arm for some cases of metastatic disease. nivolumab and pembrolizumab are humanized igg4 antipd-1 monoclonal antibodies. blockade occurs via programmed death-ligand 1 to pd-1 on cells, a process that facilitates activation of t lymphocytes, allowing the immune system to attack cancerous cells. 1 more than 40% of melanoma patients treated with anti-pd-1 therapy develop dermatologic complications. 2 the cutaneous manifestations associated with anti-pd-1 therapy are generally self-limited and mild and can be managed conservatively. the most commonly reported cutaneous side effects in melanoma patients were a nonspecific macular and papular rash with pruritus, a lichenoid or psoriasiform drug eruption, and vitiligo. 2 development of blistering disease associated with the use of anti-pd-1 therapy has not commonly been abstract monoclonal antibodies against pd-1 are becoming increasingly important agents in the oncologist's armamentarium against a variety of cancers, including melanoma and squamous cell carcinoma. most reported cutaneous reactions to these agents are mild and resolve with a conservative treatment approach. we present two cases of patients treated with anti-pd-1 agents who developed bullous pemphigoid shortly after initiation of therapy. we then review the literature of anti-pd-1-associated bullous pemphigoid, which is likely a bona fide side effect of anti-pd-1 therapy. finally, we discuss management of these cases, where the risks of bullous pemphigoid must be weighed against the benefits of anti-pd-1 treatment. as the number of indications for pd-1 monoclonal antibodies expands, dermatologists will need to recognize their cutaneous adverse events and assist oncologists in the management of such complications. introduction skin may 2018 volume 2 issue 3 copyright 2018 the national society for cutaneous medicine 176 reported to date; however, recent reports that bullous pemphigoid (bp) may be a rare side effect of anti-pd-1 therapy continue to accumulate. in this review, we present two patients who developed bp shortly after starting nivolumab. we then review the literature of anti-pd-1-associated bp. a discussion of management and treatment options follows. an 80-year-old white male presented with stage iv cutaneous squamous cell carcinoma with disease burden in the axillary lymph node basin, lungs, mediastinum, pleura, and liver. he had previously failed three months of therapy with carboplatin, paclitaxel, and cetuximab, and was subsequently started on nivolumab. seven months later, the patient developed a pruritic rash on his trunk and extremities that was histopathologically consistent with a lichenoid drug eruption. he was treated with topical triamcinolone ointment 0.1% and clobetasol ointment 0.05%. six weeks later, the patient presented with bullae clinically consistent with bp (figure 1). biopsy confirmed bp with blister cavities, eosinophils, and strong linear deposition of c3 at the dermal-epidermal junction. nivolumab was discontinued and, given his multiple comorbidities, he was treated with a steroid taper and dapsone. after several weeks of treatment with dapsone, he developed a hemolytic anemia and this agent was discontinued. the bp remained controlled on 10 mg prednisone daily with sporadic use of topical clobetasol. five months after discontinuation of nivolumab, the patient was stable without evidence of disease progression. figure 1. tense fluid-filled blisters with an erythematous underlay and several crusted papules and excoriations present on the extremities an 85-year-old white male undergoing treatment for metastatic braf-negative melanoma developed non-pruritic blisters on his trunk and extremities 8 to 9 weeks after starting nivolumab. the blisters were tense and clinically consistent with bp (figure 2). initial biopsy was equivocal, but repeat biopsy during a time of relative flaring was consistent with bp on both h&e and dif. the patient substantially improved following discontinuation of nivolumab therapy. the addition of dapsone and topical clobetasol case series: patient 1 case series: patient 2 skin may 2018 volume 2 issue 3 copyright 2018 the national society for cutaneous medicine 177 ointment 0.05% significantly improved the extent and severity of his rash. the burden of his bp is currently limited to minimal red patches with no bullae present, and a dapsone taper is planned. figure 2. several tense fluid-filled blisters with crusted pink papules and red plaques diffusely on the body when combined with the existing literature, these two cases add to a growing body of evidence surrounding a unique side effect of pd-1 antagonists (table 1). to date, the most common cutaneous adverse events associated with these agents are a nonspecific macular and papular rash or a lichenoid eruption. 2 keen clinical judgment is needed given the numerous variables involved, including the timing of the rash in the treatment course, the clinical status of the patient, any known allergies or previous adverse drug reactions, and the likelihood of successfully managing the rash. recognizing the development of a blistering disease as a distinct entity separate from drug-induced dermatitis is important, as a change in cancer therapy may be indicated depending on its severity. our patients add to the previous literature and combine for a total of 18 cases of pd-1 antagonist-associated bp (11 nivolumab, 6 pembrolizumab, 1 durvalumab). the median age of patients was 73.5 (range of 42 to 85), and the median number of weeks of anti-pd-1 treatment prior to onset of bp was 17 (range of 3 to 91). before developing bp, many patients had earlier cutaneous symptoms, such as a pruritic maculopapular rash or a lichenoid drug eruption. discussion skin may 2018 volume 2 issue 3 copyright 2018 the national society for cutaneous medicine 178 table 1. details of 18 reported cases of bullous pemphigoid developing in the setting of pd-1 checkpoint inhibitor therapy f = female; m = male; bp = bullous pemphigoid; nivo = nivolumab; pembro = pembrolizumab; durva = durvalumab; iv = intravenous. skin may 2018 volume 2 issue 3 copyright 2018 the national society for cutaneous medicine 179 treatment regimens have included a combination of oral and topical corticosteroids, often in conjunction with discontinuation of the anti-pd-1 therapy. in situations where the anti-pd-1 therapy is ineffective and did not achieve the desired result, discontinuation is clearly warranted. however, in the context of a clinical response to anti-pd-1 therapy, discontinuing the agent is challenging, and the risks of continued treatment must be carefully weighed against its benefits. as a further complication, treatment with corticosteroids is potentially problematic when using antipd1 agents due to the theoretical risk of diminishing the immunomodulatory actions of such drugs. topical steroids are generally first-line treatment for bp and are largely safe due to their limited systemic absorption. in contrast, some authors have avoided prolonged use of systemic corticosteroids given their adverse effects. in one case, the authors avoided systemic corticosteroids by using rituximab, which was started after discontinuation of nivolumab and led to resolution of bp. 3 in another, the authors were able to reintroduce nivolumab with concurrent omalizumab while using systemic steroids to control the patient’s bp. 4 future studies are needed to better define the efficacy of using targeted immunotherapy alongside anti-pd-1 treatment. with an increasing number of indications for treatment, use of anti-pd-1 agents by oncologists and dermatologists will become increasingly common. individuals with metastatic disease who have failed one or more therapies frequently have several comorbidities associated with their primary oncologic process, further complicating management considerations. the population at risk for bp is also elderly and therefore at an increased risk for comorbid conditions like hypertension, thromboembolism, and cardiovascular disease. 12 going forward, dermatologists will play a critical role in the management of patients taking anti-pd-1 agents, as optimizing quality of life and treatment will need to take into account each patient’s cutaneous adverse effects within the context of a broader medical picture. conflict of interest disclosures: none funding: none corresponding author: cristopher c. briscoe, jd 660 s. euclid ave campus box 8123 st. louis, mo 63110 314-362-9859 (office) briscoec@wustl.edu references: 1. pardoll dm. the blockade of immune checkpoints in cancer immunotherapy. nat rev cancer. 2012;12(4):252–264. 2. sibaud v, meyer n, lamant l, vigarios e, mazieres j, delord jp. dermatologic complications of anti-pd-1/pd-l1 immune checkpoint antibodies. curr opin oncol. 2016;28(4):254–263. 3. sowerby l, dewan ak, granter s, gandhi l, leboeuf nr. rituximab treatment of nivolumab-induced bullous pemphigoid. jama dermatol. 2017;153(6):603–605. 4. damsky w, kole l, tomayko mm. development of bullous pemphigoid during nivolumab therapy. jaad case rep. 2016;2(6):442–444. skin may 2018 volume 2 issue 3 copyright 2018 the national society for cutaneous medicine 180 5. naidoo j, schindler k, querfeld c, busam k, cunningham j, page db, postow ma, weinstein a, lucas as, ciccolini kt, quigley ea, lesokhin am, paik pk, chaft je, segal nh, d'angelo sp, dickson ma, wolchock jd, lacouture me. autoimmune bullous skin disorders with immune checkpoint inhibitors targeting pd-1 and pd-l1. cancer immunol res. 2016;4(5):383–389. 6. kwon cw, land as, smoller br, scott g, beck la, mercurio mg. bullous pemphigoid associated with nivolumab, a programmed cell death 1 protein inhibitor. j eur acad dermatol venereol. 2017;31(8):e349-e350. 7. jour g, glitza ic, ellis rm, torrescabala ca, tetzlaff mt, li jy, nagarajan p, huen a, aung pp, ivan d, drucker cr, prieto vg, rapini rp, patel a, curry jl. autoimmune dermatologic toxicities from immune checkpoint blockade with anti-pd-1 antibody therapy: a report on bullous skin eruptions. j cutan pathol. 2016;43(8):688–696. 8. mochel mc, ming me, imadojemu s, gangadhar tc, schuchter lm, elenitsas r, payne as, chu ey. cutaneous autoimmune effects in the setting of therapeutic immune checkpoint inhibition for metastatic melanoma. j cutan pathol. 2016;43(9):787–791. 9. parakh s, nguyen r, opie jm, andrews mc. late presentation of generalised bullous pemphigoid-like reaction in a patient treated with pembrolizumab for metastatic melanoma. australas j dermatol. 2017;58(3):e109-e112. 10. hwang sj, carlos g, chou s, wakade d, carlino ms, fernandez-peñas p. bullous pemphigoid, an autoantibody-mediated disease, is a novel immune-related adverse event in patients treated with anti-programmed cell death 1 antibodies. melanoma res. 2016;26(4):413– 416. 11. carlos g, anforth r, chou s, clements a, fernandez-peñas p. a case of bullous pemphigoid in a patient with metastatic melanoma treated with pembrolizumab. melanoma res. 2015;25(3):265–268. 12. cugno m, marzano av, bucciarelli p, balice y, cianchini g, quaglino p, calzavara pinton p, caproni m, alaibac m, de simone c, patrizi a, cozzani e, papini m, tedeschi a, berti e, rosendaal fr. increased risk of venous thromboembolism in patients with bullous pemphigoid. the inventep (incidence of venous thromboembolism in bullous pemphigoid) study. thromb haemost. 2016;115(1):193–199. powerpoint presentation early insights into the characteristics of tralokinumab patients in a real-world setting in the united states raj chovatiya1, sanjeev balu2, yestle kim2, amanda g. althoff3, lawrence rasouliyan3 1. northwestern university feinberg school of medicine, chicago, il; 2. leo pharma, madison, nj; 3. omny health, atlanta, ga table 2. baseline demographic characteristics at index tralokinumab prescription conclusions • this study provides early insights into the baseline characteristics of tralokinumab patients in a real-world setting in the us • while many characteristics were similar between biologic-naïve and biologicexperienced patients, a higher proportion of biologic-experienced patients had a greater degree of documented disease severity • understanding the types of patients who were being prescribed tralokinumab may help identify other patients who may benefit from tralokinumab to manage their moderateto-severe ad • additional real-world studies are required to observe the changes in clinical outcomes after the initiation of tralokinumab over a longer period of time objective the objective of this study was to understand the demographic, medical history, and clinical baseline characteristics of adult patients who were prescribed tralokinumab for the treatment of ad in a realworld setting. materials and methods • this retrospective, observational, descriptive study used electronic health record (ehr) data from the omny health platform • the omny health platform is comprised of approximately 1,500 dermatologists and clinicians from integrated delivery networks and ambulatory dermatology practices in the us • patients who met both of the following criteria were included: • ever had a prescription for tralokinumab from february 2022 to september 2022 • 18 years or older at the date of first the tralokinumab prescription • patients were further divided into two groups for comparative analysis: biologic-naïve and biologicexperienced. the biologic-experienced group was composed of patients who had a history of dupilumab prescription in their medical history, as it was the only us-approved biologic for ad prior to tralokinumab • deidentified ehr data was summarized to report descriptive statistics of the patient characteristics • the study index date was the date of the first tralokinumab prescription • baseline clinical characteristics, demographic, and prescription data were collected from the index date and the time period preceding the index date • all variables were derived from ehrs that were populated during patient encounters in the real-world healthcare setting: • patient demographics (age, gender, race, and weight) • treatment characteristics (dose and prescriber) • disease activity metrics (body surface area [bsa], investigator’s global assessment [iga], itch numerical rating scale [nrs] score) • comorbidities • treatment history and concomitant medications results patient population • as of september 2022, 195 adult patients met the criteria for this analysis (table 1) • of the 195, 105 (54%) had a previous prescription of dupilumab (biologic-experienced) disclosures rc has served as an advisory board member, consultant, and/or investigator for abbvie, apogee, arcutis, arena, argenx, aslan, beiersdorf, boehringer ingelheim, bristol myers squibb, cara therapeutics, dermavant, eli lilly and company, epi health, incyte, leo pharma, l’oréal, national eczema association, pfizer inc., regeneron, sanofi, and ucb, and speaker for abbvie, arcutis, dermavant, eli lilly and company, epi health, incyte, leo pharma, pfizer inc., regeneron, sanofi, and ucb. sb and yk are employees of leo pharma. aga and lr are employees of omny health and have received research funding from leo pharma. introduction • tralokinumab-ldrm (adbrytm) was approved in the united states (us) in december 2021 for the treatment of moderate-to-severe atopic dermatitis (ad) in adult patients • real-world characteristics of patients prescribed tralokinumab are not yet understood comorbidities and treatment history • in the entire cohort, the most documented comorbidities were systemic infection and skin infection (figure 1) • a higher proportion of biologic-experienced patients had systemic infection (29.5%) and skin infection (20.0%) compared to the biologic-naïve patients (16.7% and 14.4%, respectively; figure 1) • history of asthma was recorded in less than 20% of the entire cohort, and it was more prevalent in biologic-experienced patients (14.3% vs 3.3%; figure 1) • overall, the most common previously used ad treatments were topical corticosteroids, topical calcineurin inhibitors, and systemic corticosteroids. all these treatments were more prevalent among the biologic-experienced vs biologic-naïve patients (table 3) patient demographics • majority of patients were female, >50 years old, and self-identified as white race (table 2) • biologic-naïve patients, on average, had a higher proportion of females and were older than biologicexperienced patients table 3. treatment history at index tralokinumab prescription clinical characteristics at baseline • dermatologists were more likely to prescribe tralokinumab to biologic-naïve patients than biologicexperienced patients (43.2% vs 30.4%); the opposite trend was observed for nurse practitioners (5.7% for biologic-naïve patients; 14.7% for biologic-experienced patients) (table 4) • among patients with available disease activity data, approximately 79% had moderate or severe ad per their recorded index iga score • the mean ad-affected bsa at index was 22.0% and the mean itch nrs score was 5.7 (range: 0 to 10) • more biologic-experienced patients had severe ad compared to their biologic-naïve counterparts, while the opposite trend was observed with moderate ad • a larger proportion of biologic-experienced patients had documented ad involvement of the face and hands compared to the biologic-naïve patients table 1. patient criteria figure 1. medical history and comorbidities at index tralokinumab prescription winter clinical dermatology conference – miami, february 1420, 2023 criteria n ever had a prescription for tralokinumab 198 and age 18 years or older at time of first tralokinumab prescription 195 biologic naïve 90 biologic experienced 105 study limitations • the omny health platform did not include all ehrs across the entire us, which may limit generalizability • as with all ehrs, clinicians may not have documented disease activity measures consistently within the structured data, resulting in missing data • other treatments, diagnoses, and health events occurring outside of these settings or outside of this time period may not have been captured in this data source; thus, only data that the provider chose to record in the structured ehr fields were available for analysis study population n = 195 biologic naive n = 90 biologic experienced n = 105 gender, n (%) n = 195 n = 90 n = 105 female 107 (54.9%) 55 (61.1%) 52 (49.5%) male 88 (45.1%) 35 (38.9%) 53 (50.5%) age (years) n = 195 n = 90 n = 105 mean (sd) 50.9 (18.2) 54.1 (18.7) 48.2 (17.5) median (q1, q3) 53.0 (36.5, 62.5) 57.5 (40.2, 66.0) 50.0 (34.0, 60.0) min, max 18, 90 20, 90 18, 90 race, n (%) n = 112 n = 47 n = 65 white 87 (77.7%) 34 (72.3%) 53 (81.5%) black or african american 18 (16.1%) 10 (21.3%) 8 (12.3%) american indian or alaska native 1 (0.9%) 1 (2.1%) 0 (0.0%) asian 3 (2.7%) 1 (2.1%) 2 (3.1%) other 3 (2.7%) 1 (2.1%) 2 (3.1%) ethnicity, n (%) n = 81 n = 39 n = 42 hispanic or latino 7 (8.6%) 2 (5.1%) 5 (11.9%) not hispanic or latino 74 (91.4%) 37 (94.9%) 37 (88.1%) region, n (%)* n = 193 n = 89 n = 104 northeast 28 (14.5%) 12 (13.5%) 16 (15.4%) southeast 83 (43.0%) 41 (46.1%) 42 (40.4%) southwest 43 (22.3%) 22 (24.7%) 21 (20.2%) midwest 37 (19.2%) 13 (14.6%) 24 (23.1%) west 2 (1.0%) 1 (1.1%) 1 (1.0%) study population n = 195 biologic naive n = 90 biologic experienced n = 105 topical corticosteroids 157 (80.5%) 69 (76.7%) 88 (83.8%) topical calcineurin inhibitors 74 (37.9%) 28 (31.1%) 46 (43.8%) systemic corticosteroids 68 (34.9%) 30 (33.3%) 38 (36.2%) ruxolitinib cream 44 (22.6%) 14 (15.6%) 30 (28.6%) crisaborole 34 (17.4%) 10 (11.1%) 24 (22.9%) systemic immunosuppressants 18 (9.2%) 7 (7.8%) 11 (10.5%) phototherapy 12 (6.2%) 3 (3.3%) 9 (8.6%) janus kinase inhibitors 3 (1.5%) 0 (0.0%) 3 (2.9%) other biologic* 3 (1.5%) 2 (2.2%) 1 (1.0%) apremilast 2 (1.0%) 1 (1.1%) 1 (1.0%) antidepressants 2 (1.0%) 0 (0.0%) 2 (1.9%) tapinarof cream 0 (0.0%) 0 (0.0%) 0 (0.0%) roflumilast cream 0 (0.0%) 0 (0.0%) 0 (0.0%) study population n = 195 biologic naive n = 90 biologic experienced n = 105 clinician taxonomy, n (%) n = 190 n = 88 n = 102 dermatology 69 (36.3%) 38 (43.2%) 31 (30.4%) physician assistant 86 (45.3%) 39 (44.3%) 47 (46.1%) nurse practitioner 20 (10.5%) 5 (5.7%) 15 (14.7%) internal medicine 1 (0.5%) 1 (1.1%) 1 (1.0%) other 1 (0.5%) 5 (5.7%) 8 (7.8%) ad-affected body surface area percent n = 83 n = 40 n = 43 mean (sd) 22.0 (19.9) 21.0 (17.2) 22.9 (22.2) median (q1, q3) 15.0 (9.5, 28.0) 20.0 (10.0, 26.0) 15.0 (8.0, 30.0) min, max 0, 100 1, 70 0, 100 investigator’s global assessment, n (%) n = 56 n = 26 n = 30 clear 3 (5.4%) 0 (0.0%) 3 (10.0%) almost clear 2 (3.6%) 2 (7.7%) 0 (0.0%) mild 7 (12.5%) 3 (11.5%) 4 (13.3%) moderate 32 (57.1%) 16 (61.5%) 16 (53.3%) severe 12 (21.4%) 5 (19.2%) 7 (23.3%) itch numerical rating scale (0 to 10 scale) n = 35 n = 19 n = 16 n 35 19 16 mean (sd) 5.7 (2.6) 6.1 (2.6) 5.2 (2.7) median (q1, q3) 6.0 (4.0, 8.0) 6.0 (4.5, 8.0) 5.0 (3.8, 7.2) min, max 1, 10 1, 10 1, 10 ad current/previous face involvement, n (%) n = 26 n = 14 n = 12 yes 4 (15.4%) 2 (14.3%) 2 (16.7%) no 22 (84.6%) 12 (85.7%) 10 (83.3%) ad current/previous hand involvement, n (%) n = 26 n = 14 n = 12 yes 11 (42.3%) 5 (35.7%) 6 (50.0%) no 15 (57.7%) 9 (64.3%) 6 (50.0%) table 4. clinical characteristics at index tralokinumab prescription *geographic region was defined based on observed values as follows: northeast (md, pa), southeast (fl, ga, nc, sc, tn, va, wv), southwest (az, tx), midwest (il, in, ks, mi, mn, mo, oh), and west (co). acknowledgement writing support was provided by yk and omny health. leo pharma sponsored this analysis and the production of this poster. *other biologics include the following: certolizumab pegol, secukinumab, etanercept, adalimumab, tildrakizumab-asmn, infliximab, brodalumab, golimumab, risankizumab-rzaa, ustekinumab, ixekizumab, and/or guselkumab 16.7% 14.4% 10.0% 3.3% 5.6% 2.2% 29.5% 20.0% 13.3% 14.3% 4.8% 6.7% 0% 5% 10% 15% 20% 25% 30% 35% any systemic infection any skin infection any cardiovascular disease asthma any oncologic disease allergic rhinitis percent of patients with history of medical condition biologic naïve (n=90) biologic experienced (n=105) skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 359 original research tumor characteristics predicting perineural invasion in cutaneous squamous cell carcinoma identified by stepwise logistic regression analysis brandon t. beal md1,2, maulik m. dhandha md2,3 , melinda b. chu md2,4, vamsi varra bs5, eric s. armbrecht phd6, jordan b. slutsky md2,7, scott w. fosko md2,8. 1department of dermatology, cleveland clinic, cleveland, oh 2department of dermatology, saint louis university, st. louis, mo 3maine-dartmouth, family medicine residency, augusta, me 4onco derm, st. louis, mo 5case western reserve university school of medicine, case western reserve, cleveland, oh 6saint louis university center for outcomes research, saint louis university, st. louis, mo 7department of dermatology, stony brook medicine, stony brook, ny 8department of dermatology, mayo clinic, jacksonville, fl perineural invasion (pninv) in cutaneous squamous cell carcinoma (cscc) has been established as a significant independent risk factor for metastasis and death.1-5 accordingly, pninv is included as a high-risk factor in the national comprehensive cancer network’s (nccn) cscc guidelines.4 while the association of pninv with poor outcomes is well known, factors contributing to the introduction background: perineural invasion (pninv) is a significant risk factor for metastasis and death in cutaneous squamous cell carcinoma (cscc). despite this known association, factors contributing to the presence of pninv are not well characterized. aims: to determine risk factors associated with the presence of pninv using the high-risk cscc criteria developed by the national comprehensive cancer network (nccn). methods: after receiving institutional review board approval for this retrospective review, the presence of nccn high-risk factors for cscc were recorded for patients treated at a tertiary referral academic medical center, from january 1, 2010 to march 31, 2012. stepwise logistic regression was used to identify factors associated with the presence of pninv. results: pninv was present in 34 of 507 (6.7%) csccs. moderately or poorly differentiated histology (p<0.001, or 6.6 [95% ci, 3.2-13.7]), acantholytic, adenosquamous, or desmoplastic subtype (p=0.01, or 1.8 [95% ci, 0.8-4.2]), and tumors in areas m (≥10mm) and h ( ≥6mm) (p =0.05, or 5.0 [95% ci, 1.2-21.0]) were significantly associated with the presence of pninv. conclusions: this data suggests clinicians should have a higher suspicion and may be able to identify pninv in high-risk cscc based on the presence of specific high-risk factors. abstract skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 360 presence of pninv in cscc are not well characterized. our aim was to determine risk factors associated with the presence of pninv using the high-risk cscc criteria developed by the nccn. after receiving institutional review board approval, electronic medical records (emr) were queried for all patients diagnosed with cscc of the head and neck treated at a tertiary referral academic medical center from january 2010 to march 2012. patients were seen across multidisciplinary settings including the departments of dermatology, otolaryngology-head and neck surgery, hematology and oncology, radiation oncology, surgical oncology, and plastic surgery. patient demographic data as well as the presence of the nccn high-risk factors for head and neck cscc were recorded. nccn defines high-risk location/size as ≥10 mm in area m (forehead, scalp, cheek, neck, and pretibia) and ≥6 mm in area h, “mask areas of the face” (central face, eyelids, eyebrows, periorbital, nose, lips [cutaneous and vermilion], chin, mandible, preauricular and postauricular skin/sulci, temple, ear), genitalia, hands, and feet. breslow depth (bd) and clark level (cl) were available for 6 of 507 tumors (1.2%); thus, tumors were not excluded if they had incomplete bd or cl. tumors with incomplete emr data, other than bd or cl, were excluded. pninv was defined as tumor cell invasion within the perineurium or endoneurium as identified on the biopsy or excision pathology, or during mohs micrographic surgery. pninv was determined by reviewing the dermatopathology and surgical pathology reports. stepwise logistic regression was used to identify nccn cscc high-risk factors associated with the presence of pninv. alpha was set at 0.05. there were a total of 520 csccs of the head and neck identified and 13 were excluded due to incomplete emr data. the analysis included 507 tumors from 471 patients. pninv was present in 34 of 507 csccs (6.7%) from 34 patients (29 male and 5 female). the average age of the pninv cohort was 77 years (sd 13.1 years). the mean size of tumors with pninv was 2.6 cm (median 1.6 cm, range 0.6-8 cm) compared to a mean of 1.3 cm (median 1.0 cm, range 0.3-8.5 cm) for the overall cohort (table 1). the majority (58.8%) of tumors with pninv were ≤ 2.0 cm. the most common anatomic locations of cscc for the overall and pninv cohorts were the ear (19.5% vs. 14.7%), scalp (15.4% vs. 17.6%), and cheek (15.0% vs. 14.7%). areas m (> 10 mm) and h (> 6 mm) contained 12 (35.3%) and 20 (58.8%) of csccs with pninv, respectively. the logistic regression model identified three statistically significant nccn high-risk factors associated with the presence of pninv in cscc: moderately or poorly differentiated histology (p<0.001, or 6.6 [95% ci, 3.213.7]), acantholytic, adenosquamous, or desmoplastic subtype (p =.01, or 1.8 [95% ci, 0.8-4.2]), and tumors fitting nccn criteria for areas m and h (p = .05 or 5.0 [95% ci, 1.2-21.0]) (table 2). results methods skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 361 table 1: nccn patient and tumor data. overall cohort n = 507 (%) pninv cohort n = 34 (%) p value location/size as a high-risk feature, no. (%) 393 (77.5) 32 (94.1) 0.03 area m >10 mma, no. (%) 137 (27.0) 12 (35.3) 0.10 area h > 6 mmb, no. (%) 256 (50.5) 20 (58.8) 0.41 moderately or poorly differentiated 72 (14.2) 16 (47.1) <.001 acantholytic, adenosquamous or desmoplastic subtypes 76 (15.0) 8 (23.5) 0.23 depth >2mm or clark level iv, vc, no. (%) 5 (1.0) 1 (2.9) 0.89 rapidly growing 78 (15.4) 12 (35.3) 0.002 poorly-defined borders 68 (13.4) 2 (5.9) 0.28 recurrence 50 (9.9) 8 (23.5) 0.014 immunosuppression 34 (6.7) 3 (8.8) 0.88 site of prior radiation therapy or chronic inflammatory process 5 (1.0) 2 (5.9) 0.04 neurological symptoms 1 (0.2) 0 (0) 1.00 vascular involvementd 1 (0.2) 1 (2.9) 0.08 pninv, perineural invasion; no., number. aarea m: ≥10 mm on the forehead, scalp, cheek, neck, and pretibia. barea h: ≥ 6 mm on the “mask areas of the face” (central face, eyelids, eyebrows, periorbital, nose, lips (cutaneous and vermilion), chin, mandible, preauricular and postauricular skin/sulci, temple, ear), genitalia, hands, and feet. c depth or clark level was rarely recorded, 6 of 507 tumors. dpninv and vascular invasion are considered as a single grouping for the nccn criteria. table 2: multivariable predictors of perineural invasion. entire cohort n = 507 (%) pninv cohort n=34 (%) p value odds ratios (95% c.i.) moderately or poorly differentiated 72 (14.2) 16 (47.1) <.001 6.6 (3.213.7) acantholytic, adenosquamous or desmoplastic subtypes 76 (15.0) 8 (23.5) 0.01 1.8 (0.84.2) location/size as a high-risk feature 393 (77.5) 32 (94.1) 0.05 5.0 (1.221.0) area m >10 mma 137 (27.0) 12 (35.3) area h > 6 mmb 256 (50.5) 20 (58.8) pninv, perineural invasion. a area m: ≥10 mm on the forehead, scalp, cheek, neck, and pretibia. b area h: ≥ 6 mm on the “mask areas of the face” (central face, eyelids, eyebrows, periorbital, nose, lips (cutaneous and vermilion), chin, mandible, preauricular and postauricular skin/sulci, temple, ear), genitalia, hands, and feet. in this study, moderately or poorly differentiated histology, acantholytic, adenosquamous, or desmoplastic subtypes, and tumors fulfilling nccn criteria for areas m and h were significantly associated with the presence of pninv in cscc (table 2). this data suggests clinicians should have a higher suspicion and may be able to identify pninv in cscc based on these specific highrisk factors. as independent risk factors for cscc, tumor size, location on the face, and moderately or poorly differentiated histology have been associated with metastasis and death,1-6 while acantholytic, adenosquamous, or desmoplastic subtypes discussion skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 362 of cscc have received considerably less attention in the literature. the identification of patients with high-risk cscc is critical to the subsequent management of these tumors, as well as improving patient outcomes. by identifying csccs with pninv and other high-risk characteristics early, prompt and aggressive management can be initiated providing patients the best outcomes possible. this includes initial treatment with complete margin assessment, such as mohs micrographic surgery, to maximize complete tumor removal. waiting until pninv is symptomatic likely means involvement of larger diameter nerves, which is associated with an aggressive clinical course.1-3,6 though further validation is needed, csccs with pninv may not possess traditional highrisk features for metastasis, such as increased size >2cm or lip location. interestingly, in the pninv cohort the majority (n=20, 58.8%) were ≤2 cm and only 1 tumor was on the lip. of note, the scalp and cheek two frequent sites for pninv in this analysis are classified in area m, which requires a larger tumor (≥ 10 mm) to be considered high-risk compared to area h (≥ 6 mm). established cscc high-risk factors excluded from the model due to lack of statistical significance with pninv included the following: poorly-defined borders, recurrence, immunosuppression, site of prior radiation therapy or chronic inflammatory process, neurologic symptoms, depth > 2mm or cl iv, v, and vascular involvement (table 1). the lack of statistical significance for many established cscc high-risk factors was unexpected, but could be related to the characteristics of the sample or its size. the excluded factors may be rare enough in presentation not to merit inclusion in the model or they may have been present, but were infrequently recorded. of note, bd and cl were rarely recorded (6 of 507 tumors, 1.2%). consequently, the minimal data on bd and cl impacted our ability to fully examine their association with pninv. in our experience, there are significant interinstitutional differences in the routine collection of bd and cl. in summary, the results reported herein are informative and advocate for clinicians having a higher suspicion for pninv in cscc with moderate or poor differentiation, acantholytic, adenosquamous, or desmoplastic subtypes, and those tumors in areas m (≥ 10 mm) and h (≥ 6 mm). additionally, we identified that tumors ≤ 2cm in diameter were often (58.8%) associated with pninv. conflict of interest disclosures: none. funding: none. corresponding author: brandon t. beal, md department of dermatology cleveland clinic 9500 euclid avenue, a60 cleveland, oh e-mail: bealb@ccf.org references: 1) rowe de, carroll rj, day cl jr. prognostic factors for local recurrence, metastasis, and survival rates in squamous cell carcinoma of the skin, ear, and lip. j am acad dermatol 1992;26(6):976-90. 2) carter jb, johnson m, chua tl, karia ps, schmults cd. outcomes of primary cutaneous squamous cell carcinoma with perineural invasion: an 11-year conclusion mailto:bealb@ccf.org skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 363 cohort study. jama dermatol 2013;149(1):35-41. 3) brougham nd, dennett er, cameron r, tan st. the incidence of metastasis from cutaneous squamous cell carcinoma and the impact of its risk factors. j surg oncol 2012;106(7):8115. 4) “nccn guidelines version 1.2016 squamous cell skin cancers.” national comprehensive cancer network. http://www.nccn.org/professionals/p hysician_gls/pdf/ squamous.pdf accessed april 1, 2016. 5) schmults cd, karia ps, carter jb, han j, qureshi aa. factors predictive of recurrence and death from cutaneous squamous cell carcinoma: a 10-year, single-institution cohort study. jama dermatol 2013;149(5):541-7. 6) campoli m, brodland dg, zitelli j. a prospective evaluation of the clinical, histologic, and therapeutic variables associated with incidental perineural invasion in cutaneous squamous cell carcinoma. j am acad dermatol. 2014 apr;70(4):630-6. synopsisobjective to assess the impact of certolizumab pegol on dermatology life quality subdomains over the course of 144 weeks of treatment in patients with moderate to severe plaque psoriasis. introduction • certolizumab pegol (czp) is an fc-free, pegylated, anti-tumor necrosis factor agent that has shown durable clinical improvements over 144 weeks of treatment in patients with moderate to severe plaque psoriasis (pso).1,2 • pso can negatively impact health-related quality of life (hrqol), with links to pain and discomfort, social stigmatization, and psychological distress.3 therefore, it is important to understand whether clinical responses translate into long-term improvements in hrqol. • here, we present dermatology life quality index (dlqi) results over 144 weeks of czp treatment to evaluate the impact of czp across different dlqi subdomains and to expand upon dlqi remission rates (dlqi 0/1) previously reported.2 materials and methods study design and patients • data were pooled from cimpasi-1 (nct02326298) and cimpasi-2 (nct02326272), phase 3 trials in adults with moderate to severe pso; detailed study designs have been described previously (figure 1).2,4 • dlqi by initial czp randomization group through week 144 is reported, as observed. • we report: – absolute scores for total dlqi and dlqi subdomains through weeks 0–144. – rate of dlqi subdomain remission, defined as a score of 0, indicating no impact of skin disease on that concept, at weeks 48 and 144. results • baseline demographics are shown in table 1 and patient numbers with available dlqi data at each week are shown in table 2. • improvements in total dlqi observed over the first 48 weeks of czp treatment were durable through to week 144 (figure 2). • across all dlqi subdomains, baseline mean scores were similar between treatment groups (table 3). • at baseline, the dlqi subdomains with the highest scores were symptoms and feelings, daily activities, and leisure, indicating greatest impact of disease on these areas (table 3). • improvements in the scores for these dlqi subdomains over the first 48 weeks were durable through to week 144 for both treatment groups (figure 3). • remission rates at week 48 across subdomains of interest were also maintained until week 144 for both treatment groups (figure 4). a. blauvelt,1 r.b. warren,2 k. reich,3 f. brock,4 f. fierens,5 v. ciaravino,6 m. lebwohl7 bmi: body mass index; bsa: body surface area; czp: certolizumab pegol; dlqi: dermatology life quality index; il: interleukin; oc: observed case; pasi: psoriasis area and severity index; pga: physician’s global assessment; pso: psoriasis; q2w: every two weeks; sd: standard deviation; tnf: tumor necrosis factor. remission is defined as a score of 0, indicating no impact of skin disease on that concept. table 2 patient numbers with available dlqi data table 3 baseline dlqi subdomain scores (oc) figure 1 cimpasi-1 and cimpasi-2 study design figure 2 total dlqi through weeks 0–144 (oc)table 1 demographic and baseline characteristics figure 4 remission rates for dlqi subdomains at week 48 and 144 (oc) figure 3 absolute scores by dlqi subdomain through weeks 0–144 (oc) aczp 200 mg q2w patients received czp 400 mg q2w at weeks 0, 2 and 4. adults with pso ≥6 months (pasi >12, bsa affected ≥10% and pga ≥3 on a 5-point scale) were enrolled. at week 48, patients entering the open-label period from blinded treatment received czp 200 mg q2w, with subsequent dose adjustments permitted. patients not achieving pasi 50 at week 16 entered the escape arm for treatment with czp 400 mg q2w; at week 48 these patients continued to receive czp 400 mg q2w or, if they achieved pasi 75, could have had their dose reduced at the investigator’s discretion. aloading dose of czp 400 mg q2w at weeks 0, 2 and 4 or weeks 16, 18 and 20. bdose adjustments were mandatory or at the discretion of the investigator, based on pasi response. aczp 200 mg q2w patients received czp 400 mg q2w at weeks 0, 2 and 4. lower scores indicate greater quality of life. all subdomains are scored 0–6 with the exception of work and school and treatment which are scored 0–3. mean ± sd unless stated czp 400 mg q2w (n=175) czp 200 mg q2wa (n=186) all czp (n=361) age (years) 45.0 ± 12.9 45.6 ± 13.2 45.3 ± 13.0 male, n (%) 103 (58.9) 125 (67.2) 228 (63.2) bmi, kg/m2 31.2 ± 7.9 32.0 ± 7.8 31.6 ± 7.8 duration of pso (years) 18.5 ± 12.6 17.7 ± 12.9 18.1 ± 12.7 pasi 19.6 ± 7.3 19.2 ± 7.2 19.4 ± 7.3 bsa (%) 23.6 ± 14.3 23.5 ± 14.9 23.5 ± 14.6 pga score, n (%) 3: moderate 126 (72.0) 128 (68.8) 254 (70.4) 4: severe 49 (28.0) 58 (31.2) 107 (29.6) total dlqi 13.7 ± 6.9 14.3 ± 7.4 14.0 ± 7.1 prior biologic use, n (%) 59 (33.7) 62 (33.3) 121 (33.5) anti-tnf 40 (22.9) 44 (23.7) 84 (23.3) anti-il17 8 (4.6) 16 (8.6) 24 (6.6) anti-il-12/il-23 10 (5.7) 3 (1.6) 13 (3.6) mean ± sd czp 400 mg q2w (n=173) czp 200 mg q2wa (n=183) all czp (n=356) symptoms and feelings 4.1 ± 1.4 4.2 ± 1.5 4.2 ± 1.4 daily activities 3.2 ± 1.7 3.2 ± 1.9 3.2 ± 1.8 leisure 2.4 ± 1.9 2.7 ± 2.0 2.5 ± 2.0 work and school 0.9 ± 1.0 0.9 ± 1.0 0.9 ± 1.0 personal relationships 1.9 ± 1.9 2.0 ± 1.9 1.9 ± 1.9 treatment 1.2 ± 1.1 1.3 ± 1.1 1.3 ± 1.1 study week 0 2 8 12 16 24 32 48 60 72 84 96 108 120 132 144 czp 400 mg q2w 173 172 171 168 170 159 152 148 140 141 136 131 124 123 114 113 czp 200 mg q2w 183 183 173 177 174 164 159 151 142 138 130 128 124 119 106 110 institutions: 1oregon medical research center, portland, or; 2dermatology centre, salford royal nhs foundation trust, manchester nihr biomedical research centre, the university of manchester, manchester, uk; 3translational research in inflammatory skin diseases, institute for health services research in dermatology and nursing, university medical center hamburgeppendorf and skinflammation® center, hamburg, germany; 4ucb pharma, slough, uk; 5ucb pharma, brussels, belgium; 6ucb pharma, colombes, france; 7icahn school of medicine at mount sinai, new york, ny presented at fall clinical dermatology conference 2020 | october 29–november 1 | las vegas, nv conclusion improvements in total dlqi were durable from week 48 to week 144 across both czp treatment groups. this pattern was reflected in the dlqi subdomains (symptoms and feelings, daily activities, and leisure) which had the greatest impact on patients’ lives at baseline. durability of dlqi improvements among patients with moderate to severe plaque psoriasis treated with certolizumab pegol: three-year results from two phase 3 trials (cimpasi-1 and cimpasi-2) references: 1gordon k. bjd 2020; doi.org/10.1111/bjd.19393; 2blauvelt a. bjd 2020; doi.org/10.1111/bjd.19314; 3bhosle mj. health qual life outcomes 2006;4:35; 4gottlieb ab. jaad 2018;79:302–14.e6; 5finlay ay. clin exp dermatol 1994;19:210–6. author contributions: substantial contributions to study conception/design, or acquisition/analysis/interpretation of data: ab, rbw, kr, fb, ff, vc, ml; drafting of the publication, or revising it critically for important intellectual content: ab, rbw, kr, fb, ff, vc, ml; final approval of the publication: ab, rbw, kr, fb, ff, vc, ml. author disclosures: ab: scientific adviser and/or clinical study investigator for abbvie, allergan, almirall, athenex, boehringer ingelheim, bristol myers squibb, dermavant, eli lilly, forte, galderma, incyte, janssen, leo pharma, novartis, pfizer, rapt, regeneron, sanofi genzyme, sun pharma, and ucb pharma; paid speaker for abbvie; rbw: consulting fees from abbvie, almirall, amgen, arena, avillion, boehringer ingelheim, bristol myers squibb, celgene, eli lilly, janssen, leo pharma, novartis, pfizer, sanofi, and ucb pharma; research grants from abbvie, almirall, amgen, celgene, eli lilly, janssen, leo pharma, novartis, pfizer, and ucb pharma; kr: served as advisor and/or paid speaker for and/or participated in clinical trials sponsored by abbvie, affibody, almirall, amgen, avillion, biogen, boehringer ingelheim, bristol myers squibb, celgene, centocor, covagen, dermira, eli lilly, forward pharma, fresenius medical care, galapagos, gsk, janssen, kyowa kirin, leo pharma, medac, msd, miltenyi biotec, novartis, ocean pharma, pfizer, regeneron, samsung bioepis, sanofi, sun pharma, takeda, ucb pharma, valeant/bausch health, and xenoport; fb, ff, vc: employees of ucb pharma; ml: employee of mount sinai which receives research funds from abbvie, amgen, arcutis, boehringer ingelheim, dermavant, eli lilly, incyte, janssen, leo pharma, ortho dermatologics, pfizer, and ucb pharma; consultant for aditum bio, allergan, almirall, arcutis, avotres, birchbiomed, bmd skincare, boehringer ingelheim, bristol myers squibb, cara therapeutics, castle biosciences, corrona, dermavant, evelo, facilitate international dermatologic education, foundation for research and education in dermatology, inozyme pharma, leo pharma, meiji seika pharma, menlo, mitsubishi pharma, neuroderm, pfizer, promius/dr. reddy’s laboratories, serono, theravance, and verrica. acknowledgements: this study was funded by ucb pharma. we thank the patients and their caregivers in addition to the investigators and their teams who contributed to this study. the authors acknowledge susanne wiegratz, msc, ucb pharma, monheim am rhein, germany for publication coordination, ruth moulson, mph, costello medical, london and joe dixon, phd, costello medical, cambridge for medical writing and editorial assistance and the costello medical design team for design support. all costs associated with development of this poster were funded by ucb pharma in accordance with the good publication practice (gpp3) guidelines. a) symptoms and feelings b) daily activities c) leisure d lq i re m is si o n r a te ( % ) 100 80 60 40 20 0 week 48 week 144 d lq i re m is si o n r a te ( % ) 100 80 60 40 20 0 week 48 week 144 d lq i re m is si o n r a te ( % ) 100 80 60 40 20 0 week 48 week 144 52.7 40.4 47.8 40.9 76.4 66.2 71.7 71.8 83.8 74.8 78.8 79.1 czp 400 mg q2w czp 200 mg q2wczp 400 mg q2w czp 200 mg q2w czp 400 mg q2w czp 200 mg q2w a) symptoms and feelings b) daily activities c) leisure open-label period with possible dose adjustment open-label period with possible dose adjustment open-label period with possible dose adjustment s u b d o m a in s c o re ( m e a n ) 6 5 4 3 2 1 0 s u b d o m a in s c o re ( m e a n ) 0 s u b d o m a in s c o re ( m e a n ) 0 czp 400 mg q2w czp 200 mg q2w czp 400 mg q2w czp 200 mg q2w czp 400 mg q2w czp 200 mg q2w 6 5 4 3 2 1 0 6 5 4 3 2 1 0 16 32 48 64 80 96 112 128 144 0 16 32 48 64 80 96 112 128 144 0 16 32 48 64 80 96 112 128 144 0.4 0.4 0.4 0.3 0.5 0.5 0.6 0.4 0.9 1.2 0.8 1.1 week weekweek open-label period with possible dose adjustment t o ta l d lq i (m e a n ) 30 25 20 15 10 5 0 czp 400 mg q2w czp 200 mg q2w 0 16 32 48 64 80 96 112 128 144 2.6 2.9 2.0 2.7 week the dlqi questionnaire is comprised of 10 questions, each providing a score of 0–3 where higher scores indicate a greater impact of skin on that aspect of a patient’s quality of life.5 here, we present analyses based on total dlqi and individual subdomains: the dlqi subdomains with the highest scores at baseline were symptoms and feelings, daily activities, and leisure. remission rates (score of 0) in these subdomains after 144 weeks of treatment for patients randomized to czp 400 mg q2w and czp 200 mg q2w were as follows: daily activities 71.7% 71.8% leisure 78.8% 79.1% symptoms and feelings 47.8% 40.9% czp 400 mg q2w czp 200 mg q2w itchy/sore/ painful stinging embarrassed/ self-conscious interference with shopping/home/ garden influence on clothes worn problems with partners/friends/ relatives any sexual di�culties • • • • • • • • • • a�ects social/ leisure activities makes it di�cult to do any sports symptoms and feelings daily activities personal relationships leisure prevents or causes problems with work or studying how much of a problem is treatment work and school treatment methods results improvements in dlqi among czp-treated patients were durable from week 48 to week 144. conclusion score range of 0–3 (1 question each) score range of 0–6 (2 questions each) <pasi 50 initial treatment period (double-blinded) screening maintenance period safety follow-up open-label extension period (dose adjustment possible)b lda 48week 32 152160 40 144 mandatory at the investigator's discretion withdrawal placebo q2w czp 400 mg q2w escape: open-label czp 400 mg q2w czp 200 mg q2w czp 200 mg q2w 1: 2 :2 ra n d o m iz a ti o n czp 400 mg q2w ≥pasi 50, <pasi 75 lda ≥pasi 75 <pasi 50 ≥pasi 75 ≥pasi 50 <pasi 75 <pasi 50 – withdrawn<pasi 50 – withdrawn ≥pasi 75 skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 13 original research genomic atypia to enrich melanoma positivity in biopsied lesions: gene expression and pathology findings from a large u.s. registry study brook brouha, md, phd1, laura k. ferris, md, phd2, maral k. skelsey3, md, gary peck, md4, jim rock, ms5, anh nguyen, bs5, zuxu yao, phd5, michael d. howell, phd5, burkhard jansen, md5, clay j. cockerell, md, mba6 1west dermatology, la jolla, ca 2department of dermatology, university of pittsburgh, pittsburgh, pa 3department of dermatology, georgetown university school of medicine, washington, dc 4dermatologic surgery center of washington, chevy chase, md 5dermtech, inc., la jolla, ca 6cockerell dermatopathology, dallas, tx melanoma is a life-threatening skin cancer where early detection and intervention can significantly improve clinical outcome and eliminate disease. an estimated 196,060 cases of melanoma will be diagnosed in the u.s. in 2020, accounting for approximately 6,850 deaths, many of which could have been prevented through early detection.1 currently, clinically suspicious pigmented abstract importance: melanoma is diagnosed in approximately 200,000 people within the us each year and is responsible for more than 6,850 deaths. currently, clinical suspicion guides biopsy decisions and melanoma is confirmed in approximately 4% of biopsied lesions. a non-invasive two-gene expression test (2-gep) was shown to enhance the physical exam by evaluating genomic atypia to guide biopsy decisions. this study examines the corresponding histopathology of real-world 2-gep-positive cases. methods: cutaneous lesions suspicious for melanoma (n=3,418) were 2-gep tested by 90 licensed clinicians in real-world practice. 2-gep-positive lesions (genomically atypical as indicated by the detection of linc and/or prame) were biopsied in 316 out of 324 (97.5%) cases and 313 pathology reports were available for analysis. results: biopsied 2-gep-positive lesions were separated into diagnostic subgroups based on corresponding pathology reports. the prevalence of melanoma in biopsies of 2-gep-positive lesions was 18.7%. gene expression of both linc and prame was present in ever-increasing percentages of melanocytic lesions as pathology reports demonstrated increasing levels of atypia. notably, 47.5% of the histopathologically-confirmed melanomas demonstrated this double positive genomic signature while 23.7% were single-positive for linc and 28.8% were single-positive for prame. discussion: these data show that biopsied 2-gep-positive lesions are enriched almost five-fold for advanced histopathologic features compared to those biopsied based solely on visual assessment criteria. the close correlation between genomic atypia and atypical pathology should be considered when planning treatment of a 2-gep-positive lesion. consideration of genomic atypia may be a superior approach to guide biopsy decisions and manage pigmented lesions. introduction skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 14 lesions are evaluated by visual assessment and corresponding histopathology. in current standard practice, approximately 4.5 million clinically suspicious pigmented lesions are biopsied each year based on visually guided biopsy decisions; however, fewer than 200,000 cases (approximately 4%) of these biopsies are confirmed as melanoma or melanoma in situ by histopathology.1 these numbers are corroborated by recent number needed to biopsy analyses where approximately 25 biopsies identified one melanoma.2,3 recent advances in genomic analysis enable earlier detection of melanoma and offer advantages over invasive biopsies and histopathology.4-8 the evaluated 2-gep test (the pigmented lesion assay, pla, dermtech, la jolla, ca) uses a non-invasive, adhesive platform to collect skin samples from lesions clinically suspicious for melanoma.4-8 rna is then isolated and analyzed for the genomic expression of prame (preferentially expressed antigen in melanoma) and linc (linc00518, long intergenic non-coding rna 518) to guide biopsy decisions and detect melanoma early.4-8 the 2-gep test has been comprehensively validated and is characterized by high sensitivity (91%), specificity (69%), and negative predictive value (99%).4 the high-performance of 2gep testing enables the combination of clinical visual assessment and non-invasive genomic assessment to more accurately guide biopsy decisions. this current study compared genomic atypia (the expression of linc and/or prame) with histopathology findings of biopsied real-world 2-geppositive cases from a large us registry study. between july 2018 and june 2019, 90 licensed providers within 53 practices throughout the us participated in this 2-gep registry study. a total of 3,418 lesions clinically suspicious for melanoma were evaluated by 2-gep testing and included in the registry.8 single-read pathology report information from multiple pathologists available for 313 of 316 2-gep positive biopsied cases, was correlated with corresponding genomic atypia 2-gep results. overall, 62.8% of assessed lesions were contributed by board certified dermatologists; 37.2% were contributed by other licensed clinicians such as primary care physicians, physician assistants and nurse practitioners. to reduce bias, the clinicians in this registry were free to submit biopsy samples to pathologists of their own choosing with no outside influence. using the 2-gep test , linc and/or prame gene expression was detected in 324 out of the 3,418 (9.5%) lesions assessed in this registry. here we focused on analyses of 2gep-positive lesions (linc and/or prame detected) that were surgically biopsied and assessed by histopathology (n=316). based on 313 corresponding pathology reports available for analysis, 2-gep-positive lesions were separated into commonly used diagnostic subgroups (figure 1). overall, 18.7% (59/316) of 2-gep positive lesions were diagnosed as melanomas with 14.9% (47/316) diagnosed as melanomas in situ and 3.8% (12/316) as invasive melanomas. we further investigated the relationship between double-gene positive (linc and prame detected) and single-gene-positive (linc or prame detected) 2-gep test results and their histopathologic assessment (table 1). gene expression of both linc and prame was ever more prevalent as corresponding histopathologic analysis methods results skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 15 figure 1. histopathology of 2-gep-positive lesions clinically suspicious of melanoma. demonstrated ever-increasing atypia. notably, both were seen in 38.3% (18/47) of in situ melanomas and in 83.3% (10/12) of invasive melanomas for a total of 47.5% (28/59) of all confirmed melanomas. linc alone was detected in 23.7% (14/59) and prame alone was detected in 28.8% (17/59) of confirmed melanomas. figure 2 summarizes key steps in routine use of the 2-gep test. this pigmented lesion shown in figure 2 as an example had some visual irregularity, a clinical history of change, but reassuring dermoscopic features. detection of both linc and prame led to a biopsy that established the diagnosis of melanoma with a breslow depth of 0.5mm (stage pt1a). management of pigmented lesions remains a challenge and each year more than 4.5 million surgical biopsies are performed on clinically suspicious pigmented lesions based on visual atypia (e.g. abcde criteria). upon subsequent histopathological assessment, approximately 4% of these lesions are confirmed to be melanoma further illustrating the challenges in the current care standard to rule out melanoma.1-3 discussion skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 16 table 1. correlation of genomic atypia (linc and prame, prame-only, linc-only gene expression in 2-gep-positive lesions) with diagnoses based on realworld single-read histopathologic assessments. dermatopathology diagnosis linc & prame prame only linc only benign nevus or solar lentigo (n=77) 19.5% (15/77) 15.6% (12/77) 64.9% (50/77) atypical nevus with mild to moderate atypia (n=112) 22.3% (25/112) 18.8% (21/112) 58.9% (66/112) atypical nevus with severe atypia (n=24) 33.3% (8/24) 16.7% (4/24) 50% (12/24) melanoma in situ (n=47) 38.3% (18/47) 34% (16/47) 27.7% (13/47) invasive melanoma pt1a (n=11) 81.8% (9/11) 9.1% (1/11) 9.1% (1/11) invasive melanoma pt2a (n=1) 100% (1/1) 0% (0/1) 0% (0/1) non-melanocytic lesion or scar (n=41) 14.6% (6/41) 19.5% (8/41) 65.9% (27/41) no pathology available (n=3) 0% (0/3) 66.7% (2/3) 33.3% (1/3) advancements in genomic technology, such as the non-invasive 2-gep test, offer clinicians the opportunity to render biopsy decisions based on genomic differences.4-8 the 2-gep test specifically analyzes the expression of the melanoma-associated genes linc and prame. while our team was the first to fully describe the expression of linc in melanoma, the expression of prame is well documented.2 prame’s importance in melanoma has been further corroborated by a growing body of evidence focused on immunohistochemistry after surgical biopsies. when used to support histopathologic diagnoses, prame staining requires a surgically obtained specimen and subjective evaluation.9 in contrast, 2-gep is a non-invasive, objective, extensively validated test characterized by high sensitivity, specificity, and negative predictive value.4-8 in this study, we demonstrate that using genomic atypia in addition to clinical concerns to guide biopsy decisions, is associated with a nearly 5-fold enrichment of melanoma in biopsy specimens. specifically, 18.7% of surgically excised 2-gep-positive lesions in this registry study, compared to 4% of lesions biopsied based on visual atypia, were histopathologically confirmed as melanoma in situ or invasive melanoma.-3 taken together with our previous reports, the 2-gep test has the potential to transform management of pigmented lesions by noninvasively guiding biopsy decisions to detect melanoma while reducing surgical biopsies by approximately 90%.7,8 an integrated approach to optimize pigmented lesion management appears well aligned with the most recent 2019 american academy of dermatology (aad) cutaneous melanoma guidelines which state “that efforts to standardize the histopathologic diagnosis and categorization of melanocytic neoplasms are underway to reduce the significant interobserver variability among pathologists. ongoing advances in genomic medicine may make many of the aforementioned issues obsolete before the next aad melanoma clinical practice guidance is issued.”10 the guidelines, updated approximately every 5 years, also recommend that, for a lesion clinically suggestive of cutaneous melanoma, an excisional/complete biopsy is ideally performed.10 data presented here demonstrate that lesions clinically suggestive of melanoma with positive genomic atypia are further enriched for histopathologic features of melanoma making an excisional/complete biopsy even more appropriate. skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 17 figure 2. example of clinical use of 2-gep. this sharply-demarcated, 6mm, homogeneous, irregularly-shaped macule with reassuring dermoscopic features had a history of change. moderate clinical suspicion was decisively augmented by a positive 2-gep result (linc and prame detected) guiding the clinician’s (b.b.) biopsy decision. genomic atypia may be a superior approach to manage pigmented lesions since lesions clinically suspicious of melanoma exist along a spectrum of genomic atypia that corresponds to increasing histologic atypia and characteristics of melanoma. the close correlation between increasing genomic atypia and melanoma-associated pathology atypia further cements utility of the 2-gep test as a non-invasive approach to detect melanoma early and guide treatment of a 2gep positive lesion. conflict of interest disclosures: bb, lkf, mks, gp and cjc are investigators, consultants or scientific advisory board members for dermtech, jr, an, zy, mdh and bj are employees at dermtech. funding: this study was supported by dermtech. corresponding author: brook brouha, md, phd west dermatology la jolla, ca email: bbrouha@gmail.com references: 1. cancer facts and figures 2020. american cancer society. https://www.cancer.org/content/dam/can cer-org/research/cancer-facts-andstatistics/annual-cancer-facts-andfigures/2020/cancer-facts-and-figures2020.pdf. accessed january 8, 2020. 2. anderson, am, matsumoto m, saul mi, secrest am, ferris lk. accuracy of skin cancer diagnosis by physician assistants compared with dermatologists in a large health care system. jama dermatol. 2018 may; 154(5):569-573. conclusion mailto:bbrouha@gmail.com https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2020/cancer-facts-and-figures-2020.pdf https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2020/cancer-facts-and-figures-2020.pdf https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2020/cancer-facts-and-figures-2020.pdf https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2020/cancer-facts-and-figures-2020.pdf https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2020/cancer-facts-and-figures-2020.pdf skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 18 3. nault a, zhang c, kim km, saha s, bennett dd, xu yg. biopsy use in skin cancer diagnosis. jama dermatol. 2015 august; 151(8):899-902. 4. gerami p, yao z, polsky d, jansen b, busam k, ho j, martini m, ferris lk. development and validation of a noninvasive 2-gene molecular assay for cutaneous melanoma. j am acad dermatol. 2017 jan;76(1):114-20 e2. [pmid: 27707590]. 5. ferris lk, moy rl, gerami p, sligh je, jansen b, yao z, cockerell cj. noninvasive analysis of high-risk driver mutations and gene expression profiles in primary cutaneous melanoma. j invest dermatol. 2019 may;139(5):1127-1134. [pmid: 30500343]. 6. ferris lk, rigel ds, siegel dm, skelsey mk, peck, gl, hren c, gorman c, frumento g, jansen b, zuxu y, rock, j, knezevich sr, cockerell cj. impact on clinical practice of a noninvasive gene expression melanoma rule-out test: 12-month follow-up of negative test results and utility data from a large us registry study. dermatol online j. 2019 may;25(5):1-8. 7. jackson cullison sr, jansen b., yao z, ferris lk. risk stratification of severely dysplastic nevi by non-invasively obtained gene expression and mutation analyses. skin. 2020 march 8;4(2):105110. 8. brouha b, ferris lk, skelsey mk, peck g, moy r, yao z, jansen b. real-world utility of a noninvasive gene expression test to rule out primary cutaneous melanoma: a large us registry study. j drugs dermatol. 2020 march; 19(3)257-262. 9. raghavan ss, wang jy, kwok s, rieger ke, novoa ra, brown ra. prame expression in melanocytic proliferations with intermediate histopathologic or spitzoid features. j cutan pathol. 2020; 47:1023-1131. 10. swetter sm, tsao h, bichakjian ck et al. guidelines of care for the management of primary cutaneous melanoma. j am acad dermatol. 2019 january; 80(1):208-250. synopsis • atopic dermatitis (ad) is associated with higher rates of anxiety and depression, likely due to a number of contributing factors such as intense itching, disrupted sleep, stigma, increased healthcare costs, and a decreased quality of life1 • lebrikizumab (leb) is a novel, high-affinity monoclonal antibody targeting il-13 that selectively prevents formation of the il-13rα1/il-4rα heterodimer receptor signaling complex while leaving endogenous regulation of il-13 intact • in a randomized, double-blinded, placebo-controlled, dose-ranging, phase 2b study of leb in patients with moderate-to-severe ad (nct03443024),² leb demonstrated dose-dependent, statistically significant improvement in the primary endpoint (percent change from baseline to week 16 in eczema area and severity index [easi]), along with a favorable safety profile objective • because patient-reported outcomes have proven to be valuable measures of treatment effect in ad, the objective here was to evaluate the impact of leb on patient-reported outcomes, including those for anxiety and depression, using data from the phase 2b study of leb in adult patients with moderate-to-severe ad methods study design • this phase 2b study consisted of a 16-week treatment period with a 16-week safety follow-up (figure 1) • patients were randomized 3:3:3:2 to subcutaneous leb 125 mg every 4 weeks (q4w; 250 mg loading dose [ld]), 250 mg q4w (500 mg ld), 250 mg every 2 weeks (q2w; 500 mg ld at weeks 0 and 2), or placebo q2w for 16 weeks • patients requiring rescue therapy were allowed to use topical corticosteroids for as brief a period as necessary and could remain in the study; those requiring systemic rescue therapy were discontinued figure 1. study design week 0 week 4 week 8 week 12 week 16 week 32 placebo q2w (n=52) leb 250 mg q2w (n=75) 500 mg ld week 0 & 2 leb 250 mg q4w (n=80) 500 mg ld week 0 leb 125 mg q4w (n=73) 250 mg ld week 0 safety follow-up to week 32 screening (≤30 days) randomized, double-blind treatmenta primary endpoint: percent change in easi from baseline at week 16 3:3:3:2 randomization n=280 apatients were seen every two weeks and received all study drug injections in the clinic. *follow-up safety visit at week 24 and a follow-up phone call at week 32; off-treatment results for select efficacy assessments were collected at week 20 and week 24 easi, eczema area and severity index; ld, loading dose; leb, lebrikizumab; q2w, every 2 weeks; q4w, every 4 weeks; wk, week efficacy and patient-reported outcomes assessments • the primary endpoint was percent change in easi from baseline at week 16 • key secondary endpoints included patient-reported outcomes: – pruritus numeric rating scale (nrs) ≥4-point improvement and percent change from baseline at week 16 – sleep-loss nrs percent change from baseline at week 16 – patient-oriented eczema measure (poem) change from baseline at week 16 – dermatology life quality index (dlqi) 0 or 1 (no impact of ad on qol) and change from baseline at week 8 and week 16 • post hoc analyses evaluated hospital anxiety and depression scale (hads) total score change from baseline at week 16 statistical analyses • analyses used the modified intention-to-treat (mitt) population (all patients who were randomized and received study drug) • missing data through week 16 were imputed using markov chain monte carlo (mcmc) multiple imputation for efficacy data • there was no imputation of missing data for patient-reported outcomes results • a total of 73, 80, 75, and 52 patients were randomized to leb 125 mg q4w, 250 mg q4w, 250 mg q2w, and placebo, respectively • week 16 completion rates were similar across all leb groups (77.3%-79.5%) and greater than placebo (44.2%) • rescue medication use was almost 3-fold higher in leb-treated patients vs. placebo-treated patients: 12.3%, 12.5%, and 13.3% for leb 125 mg q4w, 250 mg q4w, 250 mg q2w, respectively, vs. 34.6% for placebo • patient demographics and baseline disease characteristics were well matched across groups (table 1) table 1. demographics and baseline characteristics placebo q2w n=52 leb 125 mg q4w n=73 leb 250 mg q4w n=80 leb 250 mg q2w n=75 baseline demographics age, mean (sd), years 42.2 (18.2) 36.7 (16.5) 40.2 (17.9) 38.9 (17.4) male, no. (%) 28 (53.8) 27 (37.0) 33 (41.3) 26 (34.7) race, no. (%) white 26 (50.0) 37 (50.7) 42 (52.5) 40 (53.3) black or african american 16 (30.8) 26 (35.6) 28 (35.0) 23 (30.7) american indian or alaska native 0 1 (1.4) 1 (1.3) 1 (1.3) asian 6 (11.5) 8 (11.0) 7 (8.8) 6 (8.0) multiple/other 4 (7.7) 1 (1.4) 2 (2.5) 5 (6.7) baseline disease characteristics disease duration, mean (sd), years 24.4 (17.4) 22.8 (15.4) 23.3 (16.7)a 22.1 (17.2) easi, mean (sd) 28.9 (11.8) 29.9 (13.5) 26.2 (10.1) 25.5 (11.2) iga, no. (%) 3, moderate 32 (61.5) 43 (58.9) 54 (67.5) 53 (70.7) 4, severe 20 (38.5) 30 (41.1) 26 (32.5) 22 (29.3) bsa involvement, mean (sd), percent 46.5 (22.7) 45.5 (24.5) 41.1 (20.9) 39.4 (21.5) pruritus nrs score, mean (sd)b 7.4 (2.4) 7.6 (2.0) 7.1 (2.4) 7.6 (1.9) sleep-loss nrs score, mean (sd)c 1.8 (1.2) 2.1 (1.0) 2.0 (1.2) 2.2 (1.2) poem total score, mean (sd) 19.4 (6.8) 21.5 (5.7)d 19.9 (6.7) 20.4 (5.7) dlqi, mean (sd) 14.1 (7.1) 14.5 (7.1)d 14.2 (7.7) 14.1 (6.9) hads total score, mean (sd) 13.6 (8.0) 12.7 (8.0) 13.5 (8.9) 12.5 (7.8) asample size is n=79; bsample sizes are as follows: n=49 for placebo and n=68, n=77, and n=69 for the 3 leb groups, respectively csample sizes are as follows: n=49 for placebo and n=68, n=77, and n=70 for the 3 leb groups, respectively dsample size is n=72. bsa, body surface area; dlqi, dermatology life quality index; easi, eczema area and severity index; iga, investigator’s global assessment; leb, lebrikizumab; nrs, numeric rating scale; poem, patient-oriented eczema measure. primary endpoint • all leb groups showed dose-dependent, statistically significant improvement in the primary endpoint vs. placebo at week 16 (least squares mean percent change in easi: leb 125 mg q4w [-62.3%; p<0.05], 250 mg q4w [-69.2%, p<0.01], 250 mg q2w [-72.1%, p<0.001] vs. placebo [41.1%]) (figure 2a) – dose-dependent differences in mean percent change in the easi were seen as early as the first visit (week 4) (figure 2b) figure 2. percent change in easi placebo q2w n=52 leb 125 mg q4w n=73 leb 250 mg q4w n=80 leb 250 mg q2w n=75 -41.1 -62.3 * -69.2 ** -72.1 *** 0 -20 -40 -60 -80 -100 l s m ea n c ha ng e fr om b as el in e (% ) at week 16 (primary endpoint) 0 -20 -40 -60 -80 -100 m ea n c ha ng e fr om b as el in e (% ) to week 16 4 8 12 16 a. b. placebo q2w (n=52) leb 125 mg q4w (n=73) leb 250 mg q4w (n=80) leb 250 mg q2w (n=75) -25.4 -31.3 -34.0 -40.6 -42.4 -53.9 -62.5 -61.5* 0 -46.5 -61.2 -64.7 -69.7** -50.4 -64.1 -73.5 -72.8*** *p<0.05, **p<0.01, and ***p<0.001 vs. placebo from least squares mean values and an analysis of covariance with a factor of treatment group and corresponding baseline easi as a covariate; statistical comparison at week 16 only. post-baseline up through week 16 visit summary statistics represent average values, obtained by averaging the summary statistics generated from each imputed dataset. easi, eczema area and severity index; leb, lebrikizumab; ls, least squares; q2w, every 2 weeks; q4w, every 4 weeks. patient-reported outcomes • leb-treated patients showed a numerically greater reduction in pruritus nrs by day 2 vs. placebo-treated patients, with further improvement across leb arms vs. placebo to week 16 as assessed by ≥4-point improvement or percent change from baseline (figure 3) – differences in the proportions of patients achieving pruritus nrs change ≥4 points at day 2: 6.3%, 5.6%, 15.3% of leb 125 mg q4w, 250 mg q4w, 250 mg q2w vs. 4.5% of placebo-treated patients, respectively figure 3. lebrikizumab improved pruritus through week 16 0 2 4 6 8 10 12 14 m ea n c ha ng e fr om b as el in e (% ) percent change from baselinechange ≥4 points p at ie nt s (% ) week week b.a. 16 20 0 -20 -40 -60 -80 -100 100 80 60 40 20 0 0 2 4 6 8 10 12 14 16 13.2 27.5 37.1 39.3 28.6 16.7 19.0 27.3 21.1 32.7 34.0 42.3 51.0 44.7 46.7 41.8 19.7 30.9 46.6 50.9 50.0 57.1 56.8 47.4 31.7 51.9 51.9 58.5 61.8 63.3 68.2 *** 70.0 -4.7 -29.6 -21.9 -25.2 -25.4 -31.3 -34.4 -38.8 -27.7 -32.0 -45.0 -53.0 -21.7 -39.6 -48.6 -45.7 -22.4 -31.3 -44.5 -57.1 -13.3 -41.2 -50.9 -60.1 -15.8 -41.9 -52.3 -63.7 6.8 ** -36.9 *** -48.6 *** -61.8 placebo q2w leb 125 mg q4w leb 250 mg q4w leb 250 mg q2w placebo q2w leb 125 mg q4w leb 250 mg q4w leb 250 mg q2w **p<0.01 and ***p<0.001 vs. placebo; panel a: from pairwise cochran-mantel-haenszel tests; panel b: from ls mean and an analysis of covariance with a factor of treatment group and corresponding baseline pruritus nrs as the covariate; statistical comparison at week 16 only. patient numbers fluctuate at each week as these are observed data. leb, lebrikizumab; ls, least squares; nrs, numeric rating scale; q2w, every 2 weeks; q4w, every 4 weeks. • by week 16, leb-treated patients showed numerically greater improvements in disease severity vs. placebo as assessed by poem change from baseline (figure 4) figure 4. lebrikizumab improved disease severity at week 16 placebo q2w (n=24) leb 125 mg q4w (n=59) leb 250 mg q4w (n=62) leb 250 mg q2w (n=59) -5.8 -8.9 -11.4 -12.4 0 -3 -6 -9 -12 -15 m ea n c ha ng e fr om b as el in e poem placebo q2w: 19.4 (6.8) baseline score mean (sd) leb 125 mg q4w: 21.5 (5.7) leb 250 mg q4w: 19.9 (6.7) leb 250 mg q2w: 20.4 (5.7) mitt population; no imputations were made for missing data; responses of “not done” were not included in summaries; statistical comparisons were not performed. leb, lebrikizumab; mitt, modified intent-to-treat; poem, patient-oriented eczema measure; q2w, every 2 weeks; q4w, every 4 weeks. • reduction in sleep-loss was numerically greater in all leb arms vs. placebo by week 1, with further improvement to week 16 – week 1 mean change from baseline: leb 125 mg q4w (-15.7%), 250 mg q4w (-9.5%), 250 mg q2w (-32.0%) vs. placebo (-2.7%) – week 16 mean change from baseline:: leb 125 mg q4w (-48.7%, n.s.), 250 mg q4w (-53.0%, p<0.05), 250 mg q2w (-64.7%, p<0.01) vs. placebo (-20.2%) • leb-treated patients showed numerically greater improvements vs. placebo in dlqi change from baseline and percentage of patients with dlqi 0/1 qol at week 8 and week 16 (figure 5) impact of lebrikizumab on patient-reported outcomes in atopic dermatitis: prospective and post hoc analyses of a phase 2b clinical trial demonstrate clinically meaningful improvements e. guttman-yassky,1 a. blauvelt,2 l. eichenfield,3 a. paller,4 a. armstrong,5 j. drew,6 r. gopalan,6 and e. simpson7 1icahn school of medicine at mount sinai, new york city, ny; 2oregon medical research center, portland, or; 3departments of dermatology and pediatrics, university of california; rady children’s hospital, san diego, ca; 4departments of dermatology and pediatrics, northwestern university feinberg school of medicine, chicago, il 5department of dermatology, keck school of medicine at university of southern california, los angeles, ca; 6dermira, inc., a wholly-owned subsidiary of eli lilly and company, menlo park, ca; 7department of dermatology, oregon health & science university, portland, or poster presented virtually at the fall clinical dermatology conference • october 29 november 1, 2020 figure 5. lebrikizumab improved dermatology health-related qol at week 8 and week 16 -3.1 -8.0 -8.6 -9.3 -5.9 -7.9 -9.2 -9.7 m ea n c ha ng e fr om b as el in e week -2 0 -10 -8 -6 -4 0 8 16 dlqi placebo q2w: 14.1 (7.1) baseline score mean (sd) leb 125 mg q4w: 14.5 (5.7) leb 250 mg q4w: 14.2 (7.7) leb 250 mg q2w: 14.1 (6.9) 30.9 22.4 19.7 5.1 39.0 32.3 13.6 16.7 p at ie nt s (% ) week 80 100 0 20 40 60 0 8 16 dlqi 0/1 placebo q2w leb 125 mg q4w leb 250 mg q4w leb 250 mg q2w mitt population; no imputations were made for missing data; responses of “not done” were not included in summaries; statistical comparisons were not performed. dlqi, dermatology life quality index; leb, lebrikizumab; mitt, modified intention-to-treat; qol, quality of life; q2w, every 2 weeks; q4w, every 4 weeks. • post hoc exploratory analyses showed a numerically greater improvement in hads total score change from baseline for leb arms compared with placebo (figure 6) figure 6. lebrikizumab improved patient-reported anxiety and depression (hads total score at week 8 and week 16) -2.6 -3.0 -3.8 -4.1 -2.7 -3.6 -3.8 -5.1 m ea n c ha ng e fr om b as el in e weeks post-baseline -1 0 -6 -5 -4 -3 -2 0 8 16 placebo q2w leb 125 mg q4w leb 250 mg q4w leb 250 mg q2w mitt population; no imputations were made for missing data; responses of “not done” were not included in summaries. hads, hospital anxiety and depression scale; leb, lebrikizumab; mitt, modified intent-to-treat; q2w, every 2 weeks; q4w, every 4 weeks. conclusions • in the phase 2b, placebo-controlled study, all leb groups showed dose-dependent and statistically significant improvement in the primary endpoint (percent change in easi from baseline at week 16) • selective blockade of il-13 with leb improved symptoms and qol in a rapid, clinically-meaningful, dose-dependent manner compared to placebo across a range of ad-specific and other measures – pruritus improved by day 2 (≥4-pt improvement on pruritus nrs) – disease severity improved at week 16 (poem) – sleep improved by week 1 with further improvement through week 16 (sleep-loss nrs) – dermatology-related qol improved by week 8 (dlqi and dlqi 0/1) – post hoc analyses showed a dose-dependent reduction in anxiety and depression with leb compared to placebo as measured by hads total score • these data highlight that selective blockade of il-13 with leb leads to clinically-relevant improvements in ad symptoms and patient-reported outcomes references 1. silverberg et al., br j dermatol., 2019;181:554-565. 2. guttman-yassky et al., jama derm., 2020;156:411-420. acknowledgments this study was funded by dermira, inc., a wholly-owned subsidiary of eli lilly and company. medical writing support was provided by prescott medical communications group (chicago, il). skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 952 compelling comments patch-type granuloma annulare with clinical and histological features of morphea: a true overlap? carlie reeves, ba, ms1, lauryn m falcone, md, phd2, colleen j beatty, md2, viktoryia kazlouskaya, md, phd2, joseph english iii, md2 1 university of mississippi medical center, jackson, ms 2 department of dermatology, university of pittsburgh, pittsburgh, pa ga is a chronic granulomatous disorder that usually presents as erythematous papules or plaques in an annular arrangement1. histologically, ga is characterized by mucin deposition, lymphohistiocytic infiltrate, and degeneration of collagen2. numerous inciting factors for ga have been reported, including viruses, arthropods, hiv, and borrelia infection1. ga often spontaneously resolves and is mostly a cosmetic concern to patients. however, some forms of ga are associated with systemic disease, such as generalized ga and diabetes mellitus (dm)3. patch-type ga is a distinct variant of this condition, presenting with large asymptomatic annular plaques4. this peculiar ga type is often misdiagnosed with other dermatoses, more commonly tinea, morphea, or mycosis fungoides. histopathologically, it also differs from classical ga, closely resembling inflammatory stages of morphea and interstitial granulomatous dermatitis of autoimmune disease, and interstitial drug eruption4. herein, we described a case of patch-type ga with overlapping features of morphea and discuss the existing literature of the topic. a 67-year-old woman with a past medical history of essential hypertension, type 2 diabetes, and hypercholesterolemia was evaluated in an outpatient dermatology clinic for an asymptomatic, erythematous rash on the trunk and legs that had been worsening abstract a 67-year-old woman was evaluated for a worsening asymptomatic rash located on her torso, back, and legs. she denied any chills or fevers and reported feeling otherwise well. clinically, large brownish, slightly atrophic plaques were seen on the torso suggestive of either morphea or a granulomatous condition. histopathologic examination revealed an increase in interstitial histiocytes infiltrating between altered collagen fibers, palisaded granulomas with increased mucin, suggestive of granuloma annulare (ga), as well as dermal sclerosis, perineural infiltrates with plasma cells and diminished cd34 counts, that are more typical for localized scleroderma/morphea. morphea and patch-type ga may be indistinguishable clinically and share some histopathological features. this case demonstrates similarities between these conditions and features of both conditions in the same patient. introduction case report skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 953 figure 1. (a): clinical photograph of left breast exhibiting erythematous skin with sharp border (b): clinical photograph exhibiting erythematous, annular patches of various sizes, located mostly on the lateral back. some patches demonstrate central clearing (arrow) (c): clinical photograph of erythematous, confluent patches that cover the majority of the right side and axilla (d): clinical photograph of the medial torso featuring a large erythematous patch with sharp borders. skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 954 figure 2. (a): marked sclerosis and thickened collagen bundles of the superficial and mid dermis zone (zone a) with foci of interstitial granulomatous infiltrate (zone b) and zones of perineural inflammation (zone c), hematoxylin eosin stain, x40. (b) higher magnification of the interstitial granulomatous infiltrate and homogenized collagen, hematoxylin eosin stain, x200. (c): higher magnification of perineural infiltrate with collections of plasma cells, hematoxylin eosin stain, x200. (d): increased amount of interstitial mucin, alcian blue stain, x100. (e): loss of cd34 immunostain in the superficial dermis, cd34 immunostain, x100. skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 955 over the previous 6 to 8 months (figure 1). the rash was characterized by large, nonscaly, brownish patches with central atrophy/clearing. laboratory evaluation was notable for low vitamin d levels. lyme disease antibodies were negative. punch biopsies from the lower back and abdomen revealed significant thickening of the dermal fibers with homogenization in the superficial dermis and thickened fat septae. there was an interstitial infiltrate of spindled histiocytes infiltrating between swollen collagen fibers, and focally increased interstitial mucin. scattered rare eosinophils were also noted as well as perineural plasma rich cell infiltrate. in addition, there is extensive sclerosis of the superficial and middle dermis with diminished cd34 counts (figure 2). periodic acid-schiff (pas) stain was used to identify any fungal microorganisms and basement membrane changes, both of which were absent. the patient was diagnosed with interstitial ga and possible morphea overlap and started on methotrexate 15 mg per week. the rash showed significant improvement on methotrexate after three months. patch-type ga is a poorly described entity. the largest clinic-morphological study of patch ga by khanna et al demonstrates the challenges in diagnosing this condition4. histopathologically, it was described to have unique features including predominantly interstitial infiltrate and presence of eosinophils and plasma cells4. the authors mention that these features were not previously described in the previous reports of patch-type ga and are usually considered features of morphea. we, additionally, found the presence of perineural infiltrates with plasma cells previously described as features of morphea5. interestingly, coexisting morphea and ga was described in a few reports in the literature. the first known case described a 62-year-old patient with linear morphea on pretibial surfaces and ga on the medial thigh6. two more patients were reported in 1999: one patient had ga on the thigh and morphea on the chest; the second patient had morphea on the right breast and lateral back and ga on the inner thigh and right shoulder2. a third report from 2019 describes a patient with morphea on the lower limbs and ga on the abdomen and dorsum of the feet7. another interesting case report described the development of morphea after granulomatous fasciitis induced by lyme8. it has been suggested that the coexistence of these conditions may be due to a common etiological link such as autoimmunity or previous injury6. antinuclear antibodies (ana) may be increased in up to half of all cases of morphea9. however, this is a nonspecific finding as even healthy individuals can have a positive ana. in our patient, ana was negative. scleroderma and centromere b antibodies, which are anas specific for systemic sclerosis, were also within normal limits10. in regard to previous injury, studies have shown that repeated friction, as occurs along the bra line and waistband area, may play a role in morphea developing at those susceptible sites11. our patient had patches along the underside of the breast which frequently contacts the bra lining (figure 1d). however, our patient also had more diffuse involvement across her back and chest in areas that would not be subject to repetitive friction. our patient had several comorbidities that may be risk factors for developing ga, discussion skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 956 including diabetes mellitus (dm) and hyperlipidemia. a 2021 study investigated the findings of 5,137 patients with ga. investigators reported that 21% of patients with ga had dm compared to the 13% seen in the control group. a larger percentage of patients with ga had hyperlipidemia compared to the control group (33% vs 28%)12. this study suggested that dm and hyperlipidemia may predispose one to ga through t-cell dysregulation. other studies have found t-helper 1 cells (th1), t-helper 2 cells (th2), and the janus kinase-signal transducer and activator of transcription (jak-stat) pathway to be implicated in dysregulation of ga13. increased expression of cytokines corresponding to the t-cell axes were noted; this is particularly true for il-4 mrna (corresponding to the th2 pathway), which exhibited a 15,600-fold increase in ga lesions versus control skin13. an interesting finding shared by ga and morphea is that both exhibit alterations in collagen and cd34 loss2,14,6. it has been proposed that the collagen degeneration seen in ga is mediated by m1 macrophages, a type of macrophage that initiates inflammation15. inflammation is then followed by an m2 macrophage mediated response, resulting in mucin deposition15. collagen degeneration can be analyzed by immunohistochemical staining for cd34. cd34 is a marker for vascular endothelial progenitors16. endothelial cell damage has been proposed as an inciting factor in developing morphea17. an important finding in morphea is the loss of cd34 dermal dendritic cells (ddcs)18. this cd34 loss is also seen in ga18. findings from an investigation that analyzed 50 skin lesions from patients with morphea suggest that a phenotypic change of cd34+ ddcs to smooth muscle actin positive (sma) myofibroblasts is responsible for the disease extent and fibrosis in morphea19. because cd34 counts are decreased in both morphea and ga, phenotypic changes of cd34+ ddcs could play a role in the overlapping nature as seen in our patient. however, it is rare for ga and morphea to occur in the same patient and even more rare for the diseases to occupy the same location. thus, more studies are needed to further discuss what etiological link, if any, may connect these two disorders. to conclude, we report a case of patch-type granuloma annulare with clinical and histopathological features of morphea. this case presents a challenging clinical and pathologic differential diagnosis and raises the possibility of an overlap of these two conditions. further studies are needed to better elucidate what etiologic link, if any, exists between these two entities. consent: all ethical standards have been maintained. patient gave consent to the production of this manuscript. conflict of interest disclosures: none funding: none corresponding author: carlie reeves, ba, ms university of mississippi medical center jackson, ms email: creeves4@umc.edu references: 1. schmieder sj, harper cd, schmieder gj. granuloma annulare. in: statpearls. treasure island (fl): statpearls publishing; april 18, 2022. 2. ben-amitai d, hodak e, lapidoth m, david m. coexisting morphoea and granuloma annulareare the conditions related? clin exp dermatol. 1999 mar;24(2):86-9. doi: 10.1046/j.13652230.1999.00425.x. pmid: 10233660. 3. agrawal p, pursnani n, jose r, farooqui m. granuloma annulare: a rare dermatological manifestation of diabetes mellitus. j family med conclusion mailto:creeves4@umc.edu skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 957 prim care. 2019 oct 31;8(10):3419-3421. doi: 10.4103/jfmpc.jfmpc_616_19. pmid: 31742181; pmcid: pmc6857419. 4. khanna u, north jp. patch-type granuloma annulare: an institution-based study of 23 cases. j cutan pathol. 2020 sep;47(9):785-793. doi: 10.1111/cup.13707. epub 2020 apr 27. pmid: 32279342. 5. dhaliwal ca, mackenzie ai, biswas a. perineural inflammation in morphea (localized scleroderma): systematic characterization of a poorly recognized but potentially useful histopathological feature. j cutan pathol. 2014 jan;41(1):28-35. doi: 10.1111/cup.12242. epub 2013 oct 24. pmid: 24117981. 6. holmes rc, meara rh. morphoea, sclerotic panatrophy and disseminated granuloma annulare. clin exp dermatol. 1983 mar;8(2):2013. doi: 10.1111/j.1365-2230.1983.tb01767.x. pmid: 6851242. 7. ağırgöl ş, yöntem ö, leblebici c, akbulut tö, demir ft, türkoğlu z. coexistence of morphea and granuloma annulare: a rare case report. sao paulo med j. 2019 jan-feb;137(1):96-99. doi: 10.1590/1516-3180.2017.0091060617. epub 2017 nov 17. pmid: 29166431. 8. christensen a, di loreto c, smitaman e, paravar t, jones ka, guma m. granulomatous fasciitis followed by morphea profunda: is granulomatous fasciitis part of a spectrum of deep morphea? a case report and review of the literature. clin case rep. 2018 jun 4;6(8):1412-1417. doi: 10.1002/ccr3.1608. pmid: 30147873; pmcid: pmc6098999. 9. adigun r, goyal a, hariz a. systemic sclerosis. 2022 may 8. in: statpearls [internet]. treasure island (fl): statpearls publishing; 2022 jan–. pmid: 28613625. 10. stochmal a, czuwara j, trojanowska m, rudnicka l. antinuclear antibodies in systemic sclerosis: an update. clin rev allergy immunol. 2020 feb;58(1):40-51. doi: 10.1007/s12016-0188718-8. pmid: 30607749. 11. grabell d, hsieh c, andrew r, martires k, kim a, vasquez r, jacobe h. the role of skin trauma in the distribution of morphea lesions: a crosssectional survey of the morphea in adults and children cohort iv. j am acad dermatol. 2014 sep;71(3):493-8. doi: 10.1016/j.jaad.2014.04.009. epub 2014 may 28. pmid: 24880663; pmcid: pmc4135004. 12. barbieri js, rosenbach m, rodriguez o, margolis dj. association of granuloma annulare with type 2 diabetes, hyperlipidemia, autoimmune disorders, and hematologic malignant neoplasms. jama dermatol. 2021 jul 1;157(7):817-823. doi: 10.1001/jamadermatol.2021.1805. pmid: 34106218; pmcid: pmc8190702. 13. min ms, wu j, he h, sanz-cabanillas jl, del duca e, zhang n, renert-yuval y, pavel ab, lebwohl m, guttman-yassky e. granuloma annulare skin profile shows activation of t-helper cell type 1, t-helper cell type 2, and janus kinase pathways. j am acad dermatol. 2020 jul;83(1):63-70. doi: 10.1016/j.jaad.2019.12.028. epub 2019 dec 20. pmid: 31870914. 14. jindal r, shirazi n, chauhan p. histopathology of morphea: sensitivity of various named signs, a retrospective study. indian j pathol microbiol 2020;63:600-3 15. joshi tp, duvic m. granuloma annulare: an updated review of epidemiology, pathogenesis, and treatment options. am j clin dermatol. 2022 jan;23(1):37-50. doi: 10.1007/s40257-02100636-1. epub 2021 sep 8. pmid: 34495491; pmcid: pmc8423598. 16. sidney le, branch mj, dunphy se, dua hs, hopkinson a. concise review: evidence for cd34 as a common marker for diverse progenitors. stem cells. 2014 jun;32(6):1380-9. doi: 10.1002/stem.1661. pmid: 24497003; pmcid: pmc4260088. 17. sartori-valinotti jc, tollefson mm, reed am. updates on morphea: role of vascular injury and advances in treatment. autoimmune dis. 2013;2013:467808. doi: 10.1155/2013/467808. epub 2013 nov 12. pmid: 24319593; pmcid: pmc3844232. 18. borretta, lisa j. md*,†; crawford, richard i. md*,† cd34 staining in disorders of collagen degeneration other than morphea, the american journal of dermatopathology: august 2020 volume 42 issue 8 p 623-624. doi: 10.1097/dad.0000000000001584 19. lee js, park hs, yoon hs, chung jh, cho s. cd34 stromal expression is inversely proportional to smooth muscle actin expression and extent of morphea. j eur acad dermatol venereol. 2018 dec;32(12):2208-2216. doi: 10.1111/jdv.15120. epub 2018 jul 6. pmid: 29888507. conclusions objective introduction results methods ● the objective of this analysis was to assess tcs use in patients with moderate-to-severe ad receiving tralokinumab combined with tcs in the ecztra 3 trial patients ● eligible patients were 18 years of age with a confirmed diagnosis of ad for 1 year and with an inadequate response to treatment with topical medications. additional eligibility requirements included an ad body surface area involvement of 10%, easi score of 12 at screening and 16 at baseline, and iga score of 3 study design 2:1 randomization washout of tcs and other ad medication 300 mg q2w after initial loading dose (600 mg) clinical response defined as iga-0/1 or easi-75 tralokinumab q2w � tcs (n=69) 16-week responders tralokinumab q4w � tcs (n=69) 1:1 re-randomization tralokinumab q2w � tcs (n=95) 16-week non-responders placebo q2w � tcs (n=41) 16-week responders tralokinumab q2w � tcs (n=79) 16-week non-responders screening initial treatment continuation treatment safety follow-up o�-treatment period 46 weeks32 weeks16 weeks0-6 weeks tralokinumab q2w � tcs placebo q2w � tcs n=253 n=127 figure 1. study design of the ecztra 3 trial 193.5 g 134.9 g 200 150 100 50 0 1-2 3-4 5-6 7-8 9-10 11-12 13-14 15-16 week c u m u la ti ve a m o u n t o f tc s , g placebo q2w � tcs (n=126) tralokinumab q2w � tcs (n=252) * * ** ** figure 2. cumulative tcs use through week 16 1–2 3–4 5–6 7–8 9–10 11–12 13–14 15–16 week 40 0 10 20 30 tralokinumab q2w + tcs (n=252) placebo + tcs (n=126) a m o u n t o f tc s u se d , g * * ** ** ***** 20.2 g 11.6 g figure 3. amount of tcs used by visit, assuming no tcs used from non-returned tubes 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 week 4 1 2 3 n u m b e r o f d a ys ( w e e kl y a ve ra g e ) w it h o u t to p ic a l t re a tm e n t u se * * * * **** ** tralokinumab q2w + tcs (n=252) placebo + tcs (n=126) figure 5. days without topical treatment use (weekly average) during the initial treatment period 100 50 60 70 80 90 40 30 20 10 0 r e sp o n d e rs , % tralokinumab q2w � tcs/ q2w � tcs tralokinumab q2w � tcs/ q4w � tcs initial/ continuation treatment n/n 43/48 38/49 62/67 59/65 iga-0/1 easi-75 89.6% 77.6% 92.5% 90.8% figure 6. proportion of tralokinumab q2w plus responders (iga-0/1 and easi-75) at week 16a who maintained their clinical response at week 32 when receiving tralokinumab q2w plus tcs or q4w plus tcs 17–18 19–20 21–22 23–24 25–26 27–28 29–30 31–32 week 10 0 20 30 tralokinumab q4w + tcs (n=65) tralokinumab q2w + tcs (n=67) a m o u n t o f tc s u se d , g figure 7. tcs use in patients receiving tralokinumab q2w or q4w during the continuation period (week 16 to 32) who achieved easi-75 at week 16 without rescue medication tralokinumab q2w + tcs (n=252) placebo + tcs (n=126) pa ti e n ts ,% pa ti e n ts , % tcs used, g 0 100 200 300 0 100 200 300 0 100 200 300 0 100 200 300 0 100 200 300 0 100 200 300 0 100 200 300 0 100 200 300 tcs used, g 0 100 200 300 0 100 200 300 0 100 200 300 0 100 200 300 0 100 200 300 0 100 200 300 0 100 200 300 0 100 200 300 0 10 20 30 40 50 60 0 10 20 30 40 50 60 29.2% 19.8% 39.9% 28.8% 41.5% 30.6% 30.3% 48.6% 26.7% 47.1% 35.0% 57.3% 32.5% 53.4% 36.7% 55.3% weeks 1–2a b weeks 3–4 weeks 5–6 weeks 7–8 weeks 9–10 weeks 11–12 weeks 13–14 weeks 15–16 weeks 1–2 weeks 3–4 weeks 5–6 weeks 7–8 weeks 9–10 weeks 11–12 weeks 13–14 weeks 15–16 figure 4. distribution of tcs use by visit (a) for tralokinumab q2w plus tcs and (b) placebo plus tcs placebo + tcs (n=127) tralokinumab q2w + tcs (n=253) table 1. patient demographics and disease characteristics at baseline dlqi, dermatology life quality index; nrs, numerical rating scale; scorad, scoring atopic dermatitis. aincludes usa and canada; bincludes belgium, germany, netherlands, poland, spain, and uk. medication, n (%) placebo + tcs (n=127) tralokinumab q2w + tcs (n=253) table 2. rescue medication use by type during the initial treatment period week 16, n (%) placebo + tcs (n=126) tralokinumab q2w + tcs (n=252) table 3. summary of adverse events in the initial 16-week treatment perioda apreferred terms according to medical dictionary for regulatory activities, version 20.0. ● tralokinumab 300 mg q2w plus tcs was significantly more efficacious than placebo plus tcs at treating moderate-to-severe ad ● the lower use of tcs by tralokinumab-treated patients compared to placebo-treated patients through the initial 16-week treatment period, and the lower use of rescue medication in the tralokinumab arm, demonstrated the potential steroid-sparing effects of tralokinumab — by week 16, tcs use was 50% higher for placebo compared to tralokinumab, suggesting the observed high placebo response could be attributed to high tcs use — for comparison, the level of tcs use (38.1 g/month)12 reported in a recent prescription database study in patients with moderate-to-severe ad was similar to that seen in the placebo-treated patients presented here ● the reduction in tcs use is important because prolonged use of tcs is associated with unwanted adverse events, especially in patients concomitantly receiving other forms of corticosteroids,8 reflecting the “real-world” setting use of topical corticosteroids with tralokinumab in adult patients with moderate-to-severe atopic dermatitis: results from the 32-week, phase 3 ecztra 3 trial jonathan i. silverberg,1 andrew e. pink,2 azra kurbasic,3 christina kurre olsen,3 stephan weidinger4 1department of dermatology, the george washington university school of medicine and health sciences, washington, dc, usa; 2st. john’s institute of dermatology, guy’s and st. thomas’ hospitals, london, uk; 3leo pharma a/s, ballerup, denmark; 4department of dermatology and allergy, university hospital schleswig-holstein, campus kiel, kiel, germany 2020 fall clinical dermatology conference, october 29-november 1, 2020, live virtual meeting ● atopic dermatitis (ad) is a chronic inflammatory skin disease1,2 characterized by eczematous lesions and multiple symptoms including pruritus, sleep disturbance, and depression.3-5 the type 2 cytokine, interleukin (il)-13, is a key driver of the underlying inflammation of ad and is overexpressed in lesional and non-lesional ad skin6,7 ● depending on the severity of ad, topical corticosteroids (tcs) are recommended as a first-line pharmacological intervention; however, tcs alone are often inadequate for the treatment of moderate-to-severe ad and prolonged use of tcs may cause unwanted adverse effects8,9 ● tralokinumab, a first-in-class, fully human monoclonal antibody, is designed to neutralize il-13, specifically inhibiting downstream il-13 signaling and thereby preventing pro-inflammatory activity6,7,10 ● the ecztra 3 trial (nct03363854) evaluated the efficacy, safety, and use of tralokinumab plus tcs, compared with placebo plus tcs, in treating patients with moderate-to-severe ad for up to 32 weeks — significantly more patients achieved the primary efficacy endpoints of an investigator’s global assessment (iga) score of 0 (clear) or 1 (almost clear) [iga-0/1] and a 75% improvement in eczema area and severity index (easi) [easi-75], with tralokinumab every 2 weeks (q2w) plus tcs compared with placebo plus tcs during the initial 16 week treatment period11 concomitant tcs use during ecztra 3 ● tcs (mometasone furoate, 0.1% cream, 180−200 g. europe: class 3 [potent]; usa: class 4 [midstrength]) was supplied proactively from randomization to the end of treatment ● throughout the entire treatment period, a thin film of the dispensed mometasone was applied by the patient once daily to active lesions as needed; patients were instructed to return used and unused tubes at each trial visit to allow measurement of the amount of tcs used ● tcs use was continually monitored for safety and appropriateness, and was discontinued gradually when control was achieved ● lower-potency tcs or topical calcineurin inhibitors could be prescribed if needed on areas where the supplied tcs was inadvisable or on areas where continued treatment with tcs was considered unsafe endpoints ● additional secondary endpoints assessed at week 16 were the amount of tcs used and the number of days without tcs use ● continuation endpoints included iga-0/1 at week 32 among patients with iga-0/1 at week 16 and easi-75 at week 32 among patients with easi-75 at week 16, both after initial randomization to tralokinumab statistical analyses ● primary endpoints for the initial 16-week treatment period were assessed using a hierarchical testing procedure and holm-bonferroni multiplicity adjustment ● the amount of tcs used and the number of days without topical treatment use were determined by a 2-week period and 1-week period, respectively. each endpoint was analyzed by a repeated measurements model with an unstructured covariance matrix and the mean modelled as: y = treatment*week + region + baseline iga. data observed after initiation of rescue treatment or after permanent discontinuation of investigational medicinal product (imp) were excluded from the analyses ● iga-0/1 and easi-75 at week 32 were summarized using descriptive statistics ● safety analyses were performed using the safety analysis set, with initial treatment and continuation treatment reported separately patient characteristics ● a total of 380 patients were randomized to receive either tralokinumab q2w plus tcs (n=253) or placebo plus tcs (n=127) over the initial 16-week treatment period ● baseline demographics and disease characteristics were similar across both treatment groups (table 1). all patients had received prior therapy, with almost all receiving tcs (98.2%); 61.1% had used systemic steroids, while cyclosporine was the most common prior oral immunosuppressant used (31.1%) *p<0.05 versus placebo plus tcs; **p<0.01 versus placebo plus tcs. assuming no non-returned tubes were used. data collected after permanent discontinuation of imp or initiation of rescue medication not included. repeated measurements model: tcs (g) = treatment*week + region + baseline iga. tcs use during the continuation treatment period ● at week 32, 89.6% and 92.5% of patients treated with tralokinumab q2w plus tcs and 77.6% and 90.8% of patients treated with tralokinumab q4w plus tcs, who responded to tralokinumab q2w plus tcs treatment at week 16, maintained an iga-0/1 and easi-75 response, respectively (figure 6) ● mean compliance with returning of tcs tubes was similar in the tralokinumab q2w plus tcs group and the placebo plus tcs group (95.1% and 97.5%, respectively data collected after permanent discontinuation of imp or initiation of rescue medication not included. repeated measurements model. tcs amount (g) = treatment*week + region + baseline iga. ● a greater proportion of patients used 5 g of tcs at week 15 to 16 with tralokinumab (55.3%) versus placebo (36.7%) (figure 4) ● the number of days without topical treatment was slightly higher in patients treated with tralokinumab plus tcs compared to the placebo group during the initial treatment period, with separation observed at week 7 and from week 9 to week 15, respectively (p0.05) (figure 5) data collected after permanent discontinuation of imp or initiation of rescue medication not included. repeated measurements model: number of days (weekly average) = treatment*week + region + baseline iga. aanalysis of patients who achieved a clinical response with tralokinumab q2w plus tcs at week 16 and were re-randomized to receive either tralokinumab q2w plus tcs or tralokinumab q4w plus tcs until week 32. the amount of tcs used by visit, assuming no tcs used from the non-returned tubes. repeated measurements model: change = treatment*week + baseline*week + baseline iga. no statistically significant differences were observed at any time point. ● in patients who did not respond to tralokinumab q2w plus tcs at week 16 and then continued with tralokinumab q2w plus tcs treatment up to week 32, tcs use increased from 13.8 g at week 16 to 15.0 g at week 32 (data not shown) ● tcs use decreased from 25.4 g to 16.3 g between weeks 16 and 32 in placebo non-responders who were assigned to tralokinumab q2w plus tcs at week 16 (data not shown) safety ● tralokinumab in combination with tcs was well tolerated in patients with moderate-to-severe ad (table 3) ● the safety profile at week 32 was comparable with the initial 16-week treatment period disclosures the tralokinumab ecztra 3 study was sponsored by leo pharma. jonathan i. silverberg has received honoraria as a consultant/advisory board member from leo pharma and acted as a consultant for, and/or received grants/honoraria from, abbvie, anaptysbio, asana biosciences, lilly, galderma research and development, glaxosmithkline, glenmark generics, kiniksa, leo pharma, medimmune, menlo therapeutics, pfizer, puricore, regeneron, and sanofi. andrew e. pink has acted as an advisor/speaker for abbvie, almirall, janssen, la roche-posay, leo pharma, lilly, novartis, pfizer, sanofi, and ucb. azra kurbasic, and christina kurre olsen are employees of leo pharma. stephan weiginder has received honoraria as an advisory board member/speaker from abbvie, lilly, la roche-posay laboratorie pharmaceutique, leo pharma, novartis, sanofi genzyme, and sanofi/regeneron, received fees as an investigator from abbvie, almirall, lilly, leo pharma, pfizer, and sanofi genzyme, and received grants/research funding from la roche-posay laboratorie pharmaceutique, leo pharma, and novartis. references 1. nutten s. ann nutr metab 2015; 66(suppl 1): 8–16. 2. weidinger s, novak n. lancet 2016; 387: 1109–1122. 3. eckert l et al. j am acad dermatol 2017; 77: 274–279.e273. 4. silverberg ji et al. ann allergy asthma immunol 2018; 121: 340–347. 5. dalgard fj et al. j invest dermatol 2015; 135: 984–991. 6. bieber t. allergy 2020; 75: 54–62. 7. tsoi lc et al. j invest dermatol 2019; 139: 1480–1489. 8. eichenfield lf et al. j am acad dermatol 2014; 71: 116–132. 9. boguniewicz m et al. j allergy clin immunol pract 2017; 5: 1519–1531. 10. popovic b et al. j mol biol 2017; 429: 208–219. 11. weidinger s et al. oral presentation at the american academy of dermatology virtual meeting, 2020. 12. choi jy et al. br j dermatol 2020; 182: 1017–25. ● patients were randomized 2:1 to receive either subcutaneous tralokinumab 300 mg q2w plus tcs, after a 600 mg loading dose of tralokinumab, or placebo plus tcs over an initial treatment period of 16 weeks (figure 1) ● at 16 weeks, tralokinumab responders (defined as being iga-0/1 and/or easi-75 responders at week 16) were re-randomized 1:1 to continuation treatment with tralokinumab q2w or every 4 weeks (q4w) plus tcs for an additional 16 weeks. placebo responders continued with placebo plus tcs and all non-responders received tralokinumab q2w plus tcs for an additional 16 weeks safety ● adverse events assessments were performed at baseline and at each visit tcs use during the initial treatment period ● cumulative tcs use was 30.3% lower at weeks 15 to 16 with tralokinumab (adjusted mean 134.9 g) versus placebo (adjusted mean 193.5 g; p=0.004) with separation observed from week 9-10 (figure 2) ● use of rescue treatment, which included higher potency tcs or systemic treatment for ad, was reported by 2.8% of patients in the tralokinumab q2w plus tcs group and 10.2% of those in the placebo plus tcs group (table 2) assuming no tcs used from the non-returned tubes. ● at weeks 15 to 16, patients in the tralokinumab group used approximately 50% less of the supplied tcs compared to patients who received placebo (tralokinumab, 11.6 g; placebo, 20.2 g; p=0.002) (figure 3) ● the high level of maintained response at week 32 with tralokinumab q2w or q4w in patients who achieved easi-75 at week 16 was not associated with an increased use of tcs (figure 7) skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 321 brief articles a rare case of multicentric reticulohistiocytosis priscilla ly bsa, paige hoyer bsa, adrian subrt mdb, brandon goodwin mdb, brent kelly mdb athe university of texas medical branch at galveston, school of medicine bthe university of texas medical branch at galveston, department of dermatology multicentric reticulohistiocytosis (mrh) is a rare, systemic inflammatory disease characterized by papulonodular skin lesions and severe destructive arthritis. though mrh primarily involves the skin and joints, it has been reported to involve nearly every organ system.1 to date, there have only been approximately 300 reported cases of this disease.2 the average onset of mrh is in the fourth decade, but there have been reports of cases in children and the elderly.36 the female to male ratio is 3:1, and there is no familial tendency.7,8 eighty-five percent of cases have been in caucasians, but there have been reports in hispanic, african american, native american, and asian individuals.9 patients with mrh often present with a symmetrical polyarthritis involving the joints of the fingers, elbows, shoulders, and knees.10 the arthritis may persist for several years before skin nodules erupt, making this disease difficult to differentiate from rheumatoid arthritis.10 the papulonodular lesions in mrh appear reddish-brown and can vary in size, involving the upper trunk, multicentric reticulohistiocytosis (mrh) is a rare, histiocytic disorder that primarily affects the skin and joints. this disease can have systemic involvement of various organ systems and has been associated with underlying malignancy. middle-aged, caucasian females are the most commonly affected demographic group in this disease. we present a case of a 56year-old african american male with debilitating joint pain and a papulonodular rash on his face, chest, arms, and hands. biopsy of skin lesions confirmed the diagnosis of multicentric reticulohistiocytosis. histological findings revealed dermal infiltrate composed of glassy histiocytes and giant cells with eosinophilic cytoplasm. the patient was started on 15 mg of methotrexate weekly, 1 mg of folic acid daily, and 60 mg of prednisone daily with mild improvement of skin lesions at one month follow-up. he expired from other comorbidities before long term treatment could be achieved. the potential for disfiguring skin lesions and debilitating arthropathy emphasizes the importance of early recognition and treatment of mrh. corticosteroids and methotrexate are recommended for patients with moderate to severe disease and have been shown to be successful in some cases. more studies are needed on patients with mrh to further elucidate the etiology and pathogenesis of this disease. abstract introduction skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 322 acral and extensor surfaces of extremities, and nail folds.11 lesions may be scattered and isolated or grouped to give a cobblestone appearance.9 when eruptions occur in the periungual region, a pathognomonic “coral bead” appearance is seen.12 constitutional symptoms such as fever, malaise, weakness, and weight loss may also be present.11 an underlying internal malignancy is associated with about 25% of cases.13 various malignancies including endometrial carcinoma, adenocarcinoma of the gastrointestinal tract, burkitt lymphoma, liver carcinoma, acute myeloid leukemia, ovarian carcinoma, melanoma, and mesothelioma have been reported.14-20 this high rate of association has led to debate of mrh being a paraneoplastic syndrome. however, there is no consistent type of neoplasm associated with mrh, and the two diseases do not always run a parallel course.21 nevertheless, ruling out malignancy in a patient with mrh is crucial. diagnosis of mrh is made with a skin biopsy that demonstrates numerous histiocytes with multinucleated giant cells and ground-glass appearing eosinophilic cytoplasm.2 the histiocytes contain periodic acid-schiff (pas) positive material.2 early and accurate diagnosis of mrh is important because untreated cases can progress to arthritis mutilans.21 despite this condition being aggressive and debilitating, the etiology of mrh remains poorly understood. further investigation is needed to better understand the phenomenon and treatment of this disease. a 56-year-old african american male presented with a 9 month history of symmetrical joint pain and a new onset rash on his face, arms, chest, and hands. his past medical history is significant for hypertension, hyperlipidemia, atrial fibrillation, and degenerative osteoarthritis of the knees. he complained of debilitating joint tenderness of his hands, shoulders, and knees which had significantly affected his mobility. he also reported subjective weight loss and generalized weakness. on physical exam, the patient had multiple erythematous papulonodular lesions distributed on his cheeks, ears, chest, arms, fingers and periungual regions (figure 1a). the rash on his chest presented in a photodistributed pattern, and the lesions on both arms were grouped to give a cobblestone appearance (figure 1b, c). he had the characteristic coral bead appearance of nodules surrounding the periungual regions (figure 1d, e). the patient also displayed limited range of motion and was unable to lift his arms over his head, make a complete fist, or ambulate freely. x-ray imaging of his shoulders, hands, and knees are shown (figure 2a, b, c). biopsy of his skin lesions revealed a diagnosis of multicentric reticulohistiocytosis. histology showed mononuclear histiocytes and multinucleated giant cells with eosinophilic cytoplasm resembling a ground glass appearance (figure 3a,b). the cells stained cd68(+) and pas(+) (figure 3c). labs revealed the patient was slightly anemic with an elevated esr and crp. he tested ana(+) with a titer of 1:640 and anti-ssa(+). labs were negative for rheumatoid factor, anti-ccp, anti-ssb, anti-dsdna, anti-sm/rnp, hcv, hbv, hiv, and tb. the patient was started on 15 mg of methotrexate weekly, 1 mg of folic acid daily, and 60 mg of prednisone daily, the latter of which was gradually tapered down to 10 mg daily. at one month case report skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 323 figure 1: multiple erythematous papules and nodules. (a) papulonodular lesions scattered on the cheeks. (b) the rash presenting in a photodistributed pattern on the chest. (c) papules on the arm are grouped to give a cobblestone appearance. (d) erythematous papules and nodules are found on the fingers. (e) a pathognomonic “coral bead” appearance is seen surrounding the periungual regions. follow up, he experienced mild improvement of his rash, with little to no improvement of his joint pain. unfortunately, the patient expired a few months later from sepsis secondary to hospital acquired pneumonia after a several week hospitalization. the autopsy report revealed glassy histiocytes characteristic of mrh found in the synovia of the knee and sternoclavicular joint. similar cells were also found infiltrating the epicardium. the lungs showed extensive involvement by a fibrosing and inflammatory process with patterns of organizing pneumonia and diffuse alveolar damage. there were numerous clusters of macrophages which may have been associated with the patient’s underlying mrh. the autopsy report did not reveal an underlying neoplasm. figure 2: x-ray imaging of the shoulder, hand, and knee. (a) osteoarthrosis and erosive changes of the acromioclavicular joint. (b) erosive changes in the mcp and pip joints. (c) severe osteoarthrosis with erosive changes in the medial compartment of the knee. a b c d e a b c skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 324 figure 3: histopathology of the skin shows dermal infiltration of mononuclear histiocytes and multinucleated giant cells with “ground-glass” cytoplasm. (a) h&e x40 (b) h&e x200 (c) ihc for cd68 x100 multicentric reticulohistiocytosis is a histiocytic disorder of unknown etiology that primarily affects the skin and joints. owing to its rarity, the diagnosis of mrh can be challenging. patients may present with symmetrical polyarthritis for several months to years before skin changes appear.10 the skin changes in mrh involve reddish-brown papulonodular lesions commonly found on the face and hands. patients may present with lesions that are several millimeters to 2 cm wide, ranging in number from a few to a hundred.22 if eruptions occur around the nail folds, a pathognomonic “coral bead” appearance is appreciated, though this only occurs in 50% of cases.11 on rare occasions, skin changes may overlap with features seen in dermatomyositis.2 for example, one case reported a photodistributed rash on the chest and neck with violaceous papules on the extensor surfaces of the hands, mimicking poikiloderma and gottron’s papules seen in dermatomyositis.23 with the variability in presentation, it is not uncommon for patients to be misdiagnosed with more prevalent diseases such as rheumatoid arthritis or dermatomyositis.24-26 increased awareness among clinicians plays an important role in treating patients with this disease. although there are no specific laboratory tests for diagnosing mrh, the workup should include labs to evaluate the presence of any autoimmune, infectious, or neoplastic conditions. mild anemia and elevated erythrocyte sedimentation rate are seen in about one half of patients.1 one third of patients may present with hyperlipidemia or a positive ppd.21 rheumatoid factor (rf) and cyclic citrullinated protein (ccp) are usually negative, but there have been reports of these labs testing positive along with other autoimmune markers.8 imaging discussion b c a skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 325 studies may play an important role in differentiating mrh from other causes of arthritis. x-rays will show erosive lesions that appear discrete and well-defined but can progress to involve the entire articular surface of involved joints.8 unlike other forms of inflammatory arthritis, osteopenia and periosteal bone formation are absent.9 definitive diagnosis of mrh is made with a skin biopsy. histopathology will demonstrate histiocytes with multinucleated giant cells and eosinophilic cytoplasm resembling a ground-glass appearance.2 immunohistochemical staining is positive for cd68.9 due to its rarity, a standardized treatment for mrh does not exist. a rheumatology consult should be considered for any patient diagnosed with this condition. in patients with mild symptomatic disease, nonsteroidal anti-inflammatory agents may be helpful.27 both systemic and intralesional steroids have been used with reported improvement in both skin and joint symptoms.11 various disease-modifying antirheumatic drugs have also been tried with success, often used in combination with steroids.8 in a review by tariq et al, methotrexate and prednisone were the most commonly used drugs to treat mrh.2 use of biologics such as etanercept, adalimumab, and infliximab for treatment has also shown positive results, though malignancy should be excluded before starting these drugs.11 without randomized control trials, it is difficult to know for sure whether improvement in symptoms is due to therapy or spontaneous remission of the disease.1 diagnostic test and treatment studies should be done to improve our understanding and management of mrh. conflict of interest disclosures: none. funding: provided through the utmb department of dermatology. corresponding author: priscilla ly the university of texas medical branch at galveston (214)235-1693 pfly@utmb.edu references: 1. rapini rp. multicentric reticulohistiocytosis. clinics in dermatology. 1993;11(1):107-111. doi:10.1016/0738-081x(93)90105-l. 2. tariq s, hugenberg st, hirano-ali sa, tariq h. multicentric reticulohistiocytosis (mrh): case report with review of literature between 1991 and 2014 with in depth analysis of various treatment regimens and outcomes. springerplus. 2016;5:180. doi:10.1186/s40064-0161874-5. 3. lesher jl, allen bs. multicentric reticulohistiocytosis. j am acad dermatol 1984;11:713-23. 4. jha vk, kumar r, kunwar a, et al. efficacy of vinblastine and prednisone in multicentric reticulohistiocytosis with onset in infancy. pediatrics. 2016;137(6). doi:10.1542/peds.20152118. 5. olson j, mann ja, white k, cartwright vw, bauer j, nolt d. multicentric reticulohistiocytosis: a case report of an atypical presentation in a 2-yearold. pediatric dermatology. 2015;32(3). doi:10.1111/pde.12531. 6. hotta m, minamimoto r, suzuki d, takahashi a. multicentric reticulohistiocytosis mimicking malignancy on 18f-fdg pet/ct. clinical nuclear medicine. 2017;42(7):567-568. doi:10.1097/rlu.0000000000001661. skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 326 7. barrow mv, holubar k (1969) multicentric reticulohistiocytosis. a review of 33 patients. medicine 48(4):287–305 8. islam ad, naguwa sm, cheema gs, hunter jc, gershwin me. multicentric reticulohistiocytosis: a rare yet challenging disease. clinical reviews in allergy & immunology. 2013;45(2):281-289. doi:10.1007/s12016-013-8362-2. 9. tajirian al, malik mk, robinsonbostom l, lally ev. multicentric reticulohistiocytosis. clinics in dermatology. 2006;24(6):486-492. doi:10.1016/j.clindermatol.2006.07.01 0. 10. webb-detiege t, sasken h, kaur p. infiltration of histiocytes and multinucleated giant cells in the myocardium of a patient with multicentric reticulohistiocytosis. jcr: journal of clinical rheumatology. 2009;15(1):25-26. doi:10.1097/rhu.0b013e31817d1197. 11. macía-villa cc, zea-mendoza a. multicentric reticulohistiocytosis: case report with response to infliximab and review of treatment options. clinical rheumatology. 2014;35(2):527-534. doi:10.1007/s10067-014-2611-5. 12. catterall md. multicentric reticulohistiocytosis a review of eight cases. clinical and experimental dermatology. 1980;5(3):267-279. doi:10.1111/j.13652230.1980.tb01705.x. 13. snow jl, muller as. malignancyassociated multicentric reticulohistiocytosis: a clinical, histological and immunophenotypic study. br j dermatol 1995; 133: 71–76. 14. malik mk, regan l, robinson-bostom l, pan td, mcdonald cj (2005) proliferating multicentric reticulohistiocytosis associated with papillary serous carcinoma of the endometrium. j am acad dermatol 53(6):1075–9 15. kishikawa t, miyashita t, fujiwara e, shimomura o, yasuhi i, niino d et al (2007) multicentric reticulohistiocytosis associated with ovarian cancer. mod rheumatol/japan rheum assoc 17(5):422–5 16. han l, huang q, liao kh, chen lj, kong wy, fu ww et al (2012) multicentric reticulohistiocytosis associated with liver carcinoma: report of a case. case rep dermatol 4(2):163–9 17. hinchman kf, wu jj, soden ce jr, waldman j, dyson sw (2008) multicentric reticulohistiocytosis associated with burkitt lymphoma and adenocarcinoma. cutis; cutan med pract 82(2):113–4 18. tirumalae r, rout p, jayaseelan e, shet a, devi s, kumar kr (2011) paraneoplastic multicentric reticulohistiocytosis: a clinicopathologic challenge. indian j dermatol venereol leprology 77(3):318–20 19. kenik jg, fok f, huerter cj, et al. multicentric reticulohistiocytosis in a patient with malignant melanoma: a response to cyclophosphamide and a unique cutaneous feature. arthritis rheum 1990;33:1047-51. 20. honeyboume d, kellett jk. a mesothelioma presenting with multicentric reticulohistiocytosis. postgrad med j 1985;61:57-9. 21. trotta f, castellino g, lo ma (2004) multicentric reticulohistiocytosis. best pract res clin rheumatol 18(5):759– 72 22. baek iw, yoo sh, yang h, park j, kim kj, cho cs. a case of multicentric skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 327 reticulohistiocytosis. mod rheumatol 27: 165-168, 2017. 23. muñoz-santos c, sàbat m, sáez a, gratacós j, luelmo j. multicentric reticulohistiocytosis-mimicking dermatomyositis. case report and review of the literature. dermatology. 2007;214(3):268–271. doi: 10.1159/000099594. 24. saba r, kwatra sg, upadhyay b, mirrakhimov ae, khan fn. multicentric reticulohistiocytosis presenting with papulonodular skin lesions and arthritis mutilans. case reports in rheumatology. 2013;2013:201563. doi:10.1155/2013/201563. 25. song sh, kim hj, kang dh, lim sy. a case of multicentric reticulohistiocytosis misdiagnosed as rheumatoid arthritis. kosin medical journal. 2012;27(2):181. doi:10.7180/kmj.2012.27.2.181. 26. fett n, liu rh. multicentric reticulohistiocytosis with dermatomyositis-like features: a more common disease presentation than previously thought. dermatology. 2011;222(2):102-108. doi:10.1159/000323254. 27. webb-detiege t, sasken h, kaur p. infiltration of histiocytes and multinucleated giant cells in the myocardium of a patient with multicentric reticulohistiocytosis. jcr: journal of clinical rheumatology. 2009;15(1):25-26. doi:10.1097/rhu.0b013e31817d1197. s2010517 fcpanp 2020 silverberg_without qr code.indd presented at the 5th fall clinical dermatology conference for pas & nps (fcpanp). background • the patient-oriented eczema measure (poem) is a validated, 7-item questionnaire, which assesses patient-reported frequency of atopic dermatitis (ad) symptoms from the previous week1–3 – the harmonising outcome measures for eczema initiative recommends poem as the core outcome instrument for measuring patient-reported ad symptoms in clinical trials4 • dupilumab is a fully human monoclonal antibody5,6 that blocks the shared receptor component for interleukin (il)-4 and il-13, thus inhibiting signaling of both il-4 and il-13, which are key and central drivers of type 2 infl ammation in multiple diseases7 • in the 52-week, phase 3, randomized, double-blinded liberty ad chronos trial (nct02260986), dupilumab with concomitant topical corticosteroids (tcs) vs placebo with tcs signifi cantly improved ad signs, symptoms, and patient quality of life with an acceptable safety profi le8 long-term effect of dupilumab with concomitant topical corticosteroids on poem in adults with moderate-to-severe atopic dermatitis: liberty ad chronos trial jonathan i. silverberg1 , benjamin lockshin2, melinda gooderham3,4, zhen chen5, abhijit gadkari5, ana b. rossi6 1george washington university school of medicine, washington, dc, usa; 2georgetown university, rockville, md, usa; 3skin centre for dermatology, peterborough, on, canada; 4queen’s university, kingston, on, canada; 5regeneron pharmaceuticals, inc., tarrytown, ny, usa; 6sanofi genzyme, cambridge, ma, usa methods study design • the detailed study design, patient population, effi cacy, and safety of the chronos study have been previously reported8 endpoints • outcomes assessed in this analysis included – least squares (ls) mean change from baseline to week 52 in total poem score – proportion of patients in severity grades classifi ed according to poem scores through week 52 – proportion of patients in each category of the 7 items of poem through week 52 0 = no days 1 = 1–2 days 2 = 3–4 days 3 = 5–6 days 4 = every day analysis • the analysis presented here is focused on the placebo + tcs group (control) and the dupilumab 300 mg q2w + tcs group (approved dose in adults) • effi cacy was analyzed in all randomized patients (full analysis set) • safety was analyzed in the safety analysis set, which included all patients who received ≥ 1 dose of study drug objective • to analyze the effect of dupilumab with concomitant tcs on poem in a 52-week, phase 3 trial in adults with moderate-to-severe ad using data from the liberty ad chronos trial screening moderate-to-severe ad for ≥ 3 years age: ≥ 18 years iga: ≥ 3 easi: ≥ 16 bsa: ≥ 10% post-treatment options: • open-label extension • safety follow-up through week 64 treatment period (52 weeks) follow-up period (12 weeks)loading dose on (day 1a ) day –35 to –1 baseline week 64week 52 r 3 3 1 dupilumab 300 mg sc qw + tcsb (n = 319) dupilumab 300 mg sc q2w + tcsb (n = 106) placebo sc qw + tcsb (n = 315) figure 1. chronos study design. adupilumab, 600 mg loading dose; placebo, matching placebo. bpatients were required to use tcs for the entire treatment period. bsa, body surface area; iga, investigator’s global assessment; easi, eczema area and severity index; r, randomization; qw, weekly; q2w, every 2 weeks; sc, subcutaneous. 0 –28 placebo qw + tcs dupilumab 300 mg q2w + tcs 299/16 102/4 w1 w2 w4 w6 w8 w12 w16 w20 w24 w28 w32 w36 w40 w44 w48 w52 297/18 101/5 272/43 99/7 249/66 98/8 241/74 94/12 212/103 93/13 189/126 92/14 174/141 90/16 160/155 88/18 152/163 87/19 145/170 85/21 136/179 84/22 128/187 84/22 125/190 82/24 123/192 84/22 121/194 84/22 0 4 8 week 12 16 20 24 28 32 36 40 44 48 52 –24 –20 –16 l s m e a n ( ± s e ) c h a n g e in t o ta l p o e m –12 –8 –13.7************ *************** ************ *** *** ** –5.9 –4 placebo qw + tcs (n = 315) dupilumab 300 mg q2w + tcs (n = 106) number of patients/ imputed subjects figure 2. change in total poem score from baseline up to week 52. **p < 0.01, ***p < 0.0001 vs placebo. se, standard error p ro p o rt io n o f p a ti e n ts ( % ) 100 80 60 40 20 0 56.8 40.6 2.5 baseline week 2 week 4 week 8 mild (0–7) moderate (8–19) severe (20–28) % of patients in poem category week 16 week 52a 33.0 54.6 12.4 35.9 46.7 17.5 41.9 40.6 17.5 51.4 30.8 17.8 68.6 18.1 13.3 b p ro p o rt io n o f p a ti e n ts ( % ) 100 80 60 40 20 0 61.3 36.8 1.9 baseline week 2 week 4 week 8 week 16 week 52 17.0 61.3 21.7 11.3 50.0 38.7 16.0 33.0 50.9 17.0 34.0 49.1 23.6 16.0 60.4 figure 3. categorical change in ad severity according to total poem score in (a) placebo + tcs group and (b) dupilumab 300 mg q2w group. missing poem scores were imputed into “severe” category. p ro p o rt io n o f p a ti e n ts ( % ) 100 80 60 40 20 0 88.9 5.7 4.4 baseline week 2 week 4 week 8 placebo qw + tcsa itchy skin disturbed sleep bleeding skin weeping/oozing skin cracked skin flaking skin dry/rough skin b c d e f g 0 days 1–2 days 3–4 days 5–6 days every day% of patients in poem category week 16 week 52 66.0 14.6 9.5 7.9 1.9 65.4 8.6 13.0 11.1 1.9 66.3 9.2 10.8 11.4 2.2 71.4 7.9 9.2 9.5 1.9 78.7 4.1 6.0 6.7 4.4 p ro p o rt io n o f p a ti e n ts ( % ) 100 80 60 40 20 0 93.4 3.8 1.9 baseline week 2 week 4 week 8 dupilumab 300 mg q2w + tcs week 16 week 52 55.7 10.4 17.9 15.1 40.6 14.2 17.0 23.6 4.7 39.6 7.5 11.3 34.0 7.5 36.8 7.5 15.1 27.4 13.2 34.0 1.9 17.0 30.2 17.0 p ro p o rt io n o f p a ti e n ts ( % ) 100 80 60 40 20 0 31.1 14.9 17.1 20.3 16.5 baseline week 2 week 4 week 8 placebo qw + tcs week 16 week 52 19.4 7.6 15.6 26.3 31.1 21.6 5.1 12.1 24.8 36.5 30.2 5.1 9.8 20.3 34.6 44.8 4.4 7.3 14.3 29.2 63.8 1.3 3.5 9.2 22.2 dupilumab 300 mg q2w + tcs p ro p o rt io n o f p a ti e n ts ( % ) 100 80 60 40 20 0 30.2 20.8 17.9 19.8 11.3 baseline week 2 week 4 week 8 week 16 week 52 9.4 8.5 14.2 34.0 34.0 7.5 6.6 8.5 24.5 52.8 12.3 4.7 1.9 17.9 63.2 15.1 2.8 4.7 13.2 64.2 20.8 1.9 1.9 9.4 66.0 p ro p o rt io n o f p a ti e n ts ( % ) 100 80 60 40 20 0 baseline week 2 week 4 week 8 placebo qw + tcs week 16 week 52 p ro p o rt io n o f p a ti e n ts ( % ) 100 80 60 40 20 0 baseline week 2 week 4 week 8 week 16 week 52 30.8 12.7 21.3 21.6 13.7 19.0 18.1 9.2 25.1 28.6 25.4 7.0 16.2 22.5 28.9 32.7 8.3 10.5 23.5 25.1 47.6 5.7 10.5 15.9 20.3 64.4 4.1 2.9 10.5 18.1 23.6 22.6 15.1 28.3 10.4 8.5 13.2 5.7 23.6 49.1 7.5 8.5 19.8 63.2 11.3 2.8 3.8 17.0 65.1 13.2 3.8 1.9 20.8 60.4 21.7 1.9 13.2 63.2 dupilumab 300 mg q2w + tcs p ro p o rt io n o f p a ti e n ts ( % ) 100 80 60 40 20 0 baseline week 2 week 4 week 8 week 16 week 52 p ro p o rt io n o f p a ti e n ts ( % ) 100 80 60 40 20 0 baseline week 2 week 4 week 8 week 16 week 52 22.5 10.2 19.7 23.5 24.1 14.6 14.3 7.6 24.1 39.4 23.2 6.0 11.1 19.7 40.0 31.4 5.4 6.7 19.0 37.5 45.1 3.5 9.8 13.7 27.9 63.8 1.64.1 8.3 22.2 26.4 11.3 11.3 29.2 21.7 7.5 12.3 2.8 18.9 58.5 8.5 6.6 1.9 16.0 67.0 12.3 2.8 1.9 13.2 69.8 15.1 1.9 17.0 65.1 21.7 2.8 12.3 62.3 placebo qw + tcs dupilumab 300 mg q2w + tcs 21.7 20.8 17.9 6.6 33.0 51.9 16.0 15.1 11.3 5.7 11.3 9.4 12.3 35.8 31.1 18.9 15.1 6.6 12.3 47.2 19.8 1.9 45.3 25.5 7.5 8.5 23.6 4.7 47.2 16.0 35.2 11.1 15.2 22.2 16.2 53.7 13.0 14.0 11.4 7.9 36.2 11.1 18.4 21.9 12.4 43.5 9.2 14.6 21.0 11.7 55.6 7.6 15.9 11.4 9.5 70.5 4.4 4.4 12.7 7.9 p ro p o rt io n o f p a ti e n ts ( % ) 100 80 60 40 20 0 baseline week 2 week 4 week 8 placebo qw + tcs week 16 week 52 p ro p o rt io n o f p a ti e n ts ( % ) 100 80 60 40 20 0 baseline week 2 week 4 week 8 dupilumab 300 mg q2w + tcs week 16 week 52 32.1 12.3 16.0 26.4 13.2 63.2 13.2 8.5 6.6 8.5 22.6 9.4 28.3 23.6 16.0 10.4 22.6 12.3 35.8 18.9 30.2 1.9 35.8 20.8 11.3 5.7 25.5 23.6 36.8 8.5 46.7 10.5 9.5 17.1 16.2 64.4 11.7 6.3 12.7 46.0 9.5 11.7 17.5 15.2 50.5 9.2 11.4 18.4 10.5 58.4 8.3 8.6 14.6 10.2 73.7 6.3 8.3 8.6 p ro p o rt io n o f p a ti e n ts ( % ) 100 80 60 40 20 0 baseline week 2 week 4 week 8 placebo qw + tcs week 16 week 52 p ro p o rt io n o f p a ti e n ts ( % ) 100 80 60 40 20 0 baseline week 2 week 4 week 8 dupilumab 300 mg q2w + tcs week 16 week 52 3.2 4.8 50.0 13.2 3.8 18.9 14.2 85.8 6.6 34.0 10.4 15.1 18.9 21.7 9.4 31.1 17.0 16.0 26.4 32.1 6.6 26.4 18.9 16.0 7.5 31.1 20.8 27.4 13.2 61.3 13.7 4.4 8.3 12.4 85.1 5.7 6.3 59.4 12.4 4.1 9.8 14.3 60.0 12.4 3.8 12.4 11.4 67.3 9.5 4.1 10.8 8.3 80.0 4.4 6.0 6.7p ro p o rt io n o f p a ti e n ts ( % ) 100 80 60 40 20 0 baseline week 2 week 4 week 8 placebo qw + tcs week 16 week 52 p ro p o rt io n o f p a ti e n ts ( % ) 100 80 60 40 20 0 baseline week 2 week 4 week 8 dupilumab 300 mg q2w + tcs week 16 week 52 2.9 2.2 2.8 3.8 figure 4. categorical change in each response on the individual questions of the poem questionnaire (a) itchy skin, (b) disturbed sleep, (c) bleeding skin, (d) weeping/oozing skin, (e) cracked skin, (f) fl aking skin, and (g) dry/rough skin. missing poem scores were imputed into “every day” category. table 1. baseline demographics and disease characteristics (full analysis set). scoring placebo qw + tcs (n = 315) dupilumab 300 mg q2w + tcs (n = 106) age, mean (sd), years – 36.6 (13.01) 39.6 (13.98) male, n (%) – 193 (61.30) 62 (58.50) total poem, mean (sd) 0–28 20.0 (5.99) 20.3 (5.68) itchy skin 0–4 3.8 (0.54) 3.9 (0.43) sleep disturbance 0–4 2.2 (1.48) 2.4 (1.39) bleeding skin 0–4 2.2 (1.44) 2.2 (1.36) weeping/oozing skin 0–4 1.8 (1.47) 1.9 (1.53) cracked skin 0–4 2.9 (1.36) 3.0 (1.28) flaking skin 0–4 3.2 (1.18) 3.2 (1.32) dry/rough skin 0–4 3.7 (0.73) 3.7 (0.75) ad severity according to poem, n (%) mild 0–7 8 (2.5) 2 (1.9) moderate 8–19 128 (40.6) 39 (36.8) severe 20–28 178 (56.8) 65 (61.3) sd, standard deviation. table 2. overall safety summary of patients during the 52-week treatment period (safety analysis set). patients with, n (%) placebo qw + tcs (n = 315) dupilumab 300 mg q2w + tcs (n = 110) dupilumab 300 mg qw + tcs (n = 315) any teae 268 (85.1) 97 (88.2) 263 (83.5) teaes leading to discontinuation 25 (7.9) 2 (1.8) 9 (2.9) death 0 0 1 (0.3) any te sae 16 (5.1) 4 (3.6) 10 (3.2) nasopharyngitisa,b 62 (19.7) 25 (22.7) 62 (19.7) dermatitis atopica,b 147 (46.7) 22 (20.0) 55 (17.5) injection-site reactiona,b 25 (7.9) 16 (14.5) 61 (19.4) conjunctivitisb,c 25 (7.9) 15 (13.6) 61 (19.4) apatients with ≥ 1 such event. bmeddra pt. cnarrow conjunctivitis including meddra pts of conjunctivitis, conjunctivitis allergic, conjunctivitis bacterial, conjunctivitis viral, and atopic keratoconjunctivitis. meddra, medical dictionary for regulatory activities; pt, preferred term; teae, treatment-emergent adverse event; te sae, treatment-emergent serious adverse event references: 1. c harman cr, et al. arch dermatol. 2004;140:1513-9. 2. s chmitt j, et al. j allergy clin immunol. 2007;120:1389-98. 3. g erbens la, et al. allergy. 2017;72:146-63. 4. c halmers jr, et al. br j dermatol. 2016;175:69-79. 5. macdonald le, et al. proc natl acad sci u s a. 2014;111:5147-52. 6. murphy aj, et al. proc natl acad sci u s a. 2014;111:5153-8. 7. gandhi na, et al. expert rev clin immunol. 2017;13:425-37. 8. blauvelt a, et al. lancet. 2017;389:2287-303. acknowledgments: data fi rst presented at the 78th annual meeting of the american academy of dermatology (aad 2020); denver, co, usa; march 20–24, 2020. research sponsored by sanofi and regeneron pharmaceuticals, inc. clinicaltrials.gov identifi er: liberty ad chronos (nct02260986). medical writing/editorial assistance provided by toby leigh bartholomew, phd, of excerpta medica, funded by sanofi genzyme and regeneron pharmaceuticals, inc. disclosures: silverberg ji: abbvie, celgene, eli lilly, gsk, incyte, kiniksa pharmaceuticals, leo pharma, realm therapeutics, regeneron pharmaceuticals, inc. – investigator; abbvie, eli lilly, galderma, gsk, incyte, kiniksa pharmaceuticals, leo pharma, medimmune (astrazeneca), menlo therapeutics, pfi zer, realm therapeutics, regeneron pharmaceuticals, inc. – consultant; regeneron pharmaceuticals, inc. – speaker. lockshin b: eli lilly, regeneron pharmaceuticals, inc. – investigator, speaker; anacor, dermira, franklin bioscience, leo pharma – investigator; abbvie – investigator, speaker, consultant. gooderham m: abbvie, akros, amgen, arcutis antiobix, boehringer ingelheim, bristol-myers squibb, celgene, coherus biosciences, dermira, eli lilly, galderma, gsk, janssen, kyowa kirin, leo pharma, merck, medimmune, novartis, pfi zer, regeneron pharmaceuticals, inc., roche, sanofi genzyme, sun pharma, ucb, valeant/bausch – investigator, advisor, and/or speaker. chen z, gadkari a: regeneron pharmaceuticals, inc. − employees and shareholders. rossi ab: sanofi genzyme − employee, may hold stock and/or stock options in the company. methods (cont.) results (cont.) effi cacy results safety conclusions • dupilumab + tcs signifi cantly improved the total poem score over the 52-week study period, and signifi cant improvements were observed in all individual domains, with most patients reporting “mild” symptoms by the end of the study • more patients receiving dupilumab + tcs vs control reported “0 days” of signs and symptoms on the 7 poem items at week 52 powerpoint presentation presented at 40th annual fall clinical dermatology conference, october 29–november 1, 2020 roflumilast cream (arq-151) improved itch severity and itch-related sleep loss in adults with chronic plaque psoriasis in a phase 2b study introduction • roflumilast cream (arq-151), a potent phosphodiesterase-4 (pde-4) inhibitor, is under investigation as a once-daily topical treatment for plaque psoriasis1,2 • in a randomized, double-blind, phase 2b trial of 331 adults with chronic plaque psoriasis, roflumilast cream administered once daily was superior to vehicle cream2 – primary endpoint of achievement of “clear” or “almost clear” skin based on investigator global assessment (iga) at week 6 was met • roflumilast 0.3%: 28.0% (p<0.001 vs vehicle) • roflumilast 0.15%: 22.8% (p=0.004 vs vehicle) • vehicle: 8.3% – treatment-related adverse events (aes), including application site pain, were uncommon and the frequency was similar in all groups • here we report the effect of roflumilast cream on itch, a highly prevalent and frequently bothersome symptom of chronic plaque psoriasis that negatively impacts quality of life,3 assessed using patient-reported outcome (pro) measures in this study objective • to assess the effect of roflumilast cream on various pros related to itch methods • design: parallel-group, randomized, double-blind, vehicle-controlled phase 2b study (clinicaltrials.gov nct03638258; figure 1)2 • location: 30 sites in the united states and canada conclusions • once-daily roflumilast cream demonstrated significant improvement in reducing itch in patients with psoriasis compared with vehicle cream – patients reported a rapid and clinically significant reduction in the severity and burden of itch – significant itch reduction occurred by week 2 and continued with further reductions through week 12 – in a subgroup of patients with greater severity of itch at baseline (wi-nrs ≥6), more than half of the patients had a substantial (≥4-point) reduction in itch by week 6, and the response rate continued to increase through week 12 – reduction in itch resulted in significant improvement in sleep loss by week 6 • roflumilast cream was well-tolerated and application site pain was uncommon and similar to vehicle table 1. baseline characteristics roflumilast 0.3% (n=109) roflumilast 0.15% (n=113) vehicle (n=109) age, mean (sd), years 51.7 (14.1) 54.4 (14.2) 55.5 (13.5) sex, male, n (%) 56 (51.4) 62 (54.9) 67 (61.5) race, n (%) white 82 (75.2) 95 (84.1) 92 (84.4) black 12 (11.0) 10 (8.8) 7 (6.4) multiple/other 15 (13.8) 8 (7.1) 10 (9.2) psoriasis-affected bsa, mean (sd), % 6.3 (4.0) 6.4 (3.9) 6.4 (3.6) iga score 2 (mild), % 15.6 15.9 10.1 3 (moderate), % 77.1 73.5 81.7 4 (severe), % 7.3 10.6 8.3 pasi, mean score (sd) 7.7 (3.6) 8.0 (3.9) 7.6 (3.1) wi-nrs score ≥6, n (%) 71 (65.1) 62 (54.9) 64 (58.7) wi-nrs, mean score* (sd) 6.1 (2.7) 5.6 (3.1) 5.9 (2.9) psd item 1, itch severity,* mean score (sd) 5.5 (2.8) 5.3 (3.1) 5.5 (3.0) psd item 2, itch burden,* mean score (sd) 5.2 (3.0) 5.2 (3.3) 5.5 (3.2) itch-related sleep loss nrs,* mean score (sd) 2.9 (3.2) 3.0 (3.2) 3.4 (3.2) data are presented for intent-to-treat population. *scale of 0 (none) to 10 (worst). bsa: body surface area; iga: investigator global assessment; nrs: numeric rating scale; pasi: psoriasis area and severity index; psd: psoriasis symptom diary; sd: standard deviation; wi-nrs: worst itch numeric rating scale. in a phase 2b study, roflumilast cream, an investigational once-daily, nonsteroidal topical pde-4 inhibitor, was effective in achieving “clear” or “almost clear” skin and improving itch and itch-related sleep loss in patients with chronic plaque psoriasis references 1. papp ka, et al. j drugs dermatol 2020;19:734-740. 2. lebwohl mg, et al. n engl j med 2020;383:229-239. 3. naegeli an, et al. int j dermatol 2015;54:715-722. 4. lebwohl m, et al. int j dermatol 2014;53:714-722. 5. strober be, et al. value health 2013;16:1014-1022. 6. strober b, et al. int j dermatol 2016;55:e147-e155. 7. kimball ab, et al. br j dermatol 2016;175:157-162. acknowledgements • this study was supported by arcutis biotherapeutics, inc. • thank you to the investigators and their staff for their participation in the trial • we are grateful to the study participants and their families for their time and commitment • writing support was provided by aleksandra adomas, phd, cmpp, touch scientific, philadelphia, pa, and funded by arcutis biotherapeutics, inc. disclosures lsg, mgl, kap, mjg, lhk, zdd, sek, dmp, ja-l, and dpt: investigator, consultant, and/or advisory board member for arcutis biotherapeutics, inc. zdd has received grant support from arcutis biotherapeutics, inc. ks, rch, ln, and drb: employees of arcutis biotherapeutics, inc. hw has a patent application relevant to this work. • itch was assessed at baseline and weeks 2, 4, 6, 8, and 12 using pro measures: – worst itch numeric rating scale (wi-nrs)3 assessed the worst itch – psoriasis symptom diary (psd) items 1 and 24-6 assessed burden and severity of itch – itch-related sleep loss nrs assessed intensity of sleep loss – all pro measures assessed itch over the previous 24 hours and were rated on a scale from 0 (no impact) to 10 (as bad as it can be) results • in total, 331 patients were randomized to roflumilast 0.3% (n=109), roflumilast 0.15% (n=113), or vehicle (n=109)2 • baseline characteristics are presented in table 1 table 2. summary of aes teae, n (%) roflumilast 0.3% (n=109) roflumilast 0.15% (n=110) vehicle (n=107) patients with any teae 42 (38.5) 30 (27.3) 32 (29.9) patients with any treatmentrelated teae 7 (6.4) 3 (2.7) 7 (6.5) patients with any saea 1 (0.9) 1 (0.9) 2 (1.9) patients who discontinued study due to aeb 1 (0.9) 0 2 (1.9) most common teae (>2% of patients in any group) upper respiratory tract infection (including viral) 9 (8.3) 8 (7.3) 4 (3.7) nasopharyngitis 4 (3.7) 3 (2.7) 4 (3.7) application site pain 2 (1.8) 1 (0.9) 3 (2.8) sinusitis 3 (2.8) 0 0 urinary tract infection 0 3 (2.7) 1 (0.9) aroflumilast 0.3%: worsening of chest pain in a patient with history of myocardial infarction; roflumilast 0.15%: melanoma (not in treatment area); vehicle group: acute infarction of left basal ganglia, spontaneous miscarriage. broflumilast 0.3%: onset of worsening psoriasis; vehicle: mood swings, contact dermatitis. data are presented for safety population. ae: adverse event; sae: serious adverse event; teae: treatment-emergent adverse event. • treatment-emergent aes were uncommon in this study and were similar across treatment groups (table 2)2 • more patients discontinued the study due to an ae in the vehicle group than in the roflumilast groups • rates of application site pain were low and similar to vehicle • 97% of aes were rated mild or moderate figure 2. wi-nrs score: “what was the worst level of itch over the past 24 hours?” data are presented for intent-to-treat population. missing data imputed using linear interpolation and last observation carried forward where linear interpolation was not computationally possible. ls: least squares; wi-nrs: worst itch numeric rating scale. *nominal p<0.05 vs vehicle assessed on a scale from 0 (no itch) to 10 (worst imaginable itch) -4 -3 -2 -1 0 baseline week 2 week 4 week 6 week 8 week 12 ls m ea n ch an ge in w in rs s co re * * * * * * * * * * • both roflumilast doses showed similar improvements in wi-nrs score and mean change from baseline in wi-nrs score was significantly superior to vehicle throughout the trial (p≤0.002; figure 2) • previous studies have shown that a 4-point change is optimal for demonstrating a clinically meaningful itch response in patients with moderate to severe plaque psoriasis7 • among patients with a wi-nrs score ≥6 at baseline (n=197/331), rates of achievement of a ≥4-point reduction from baseline in wi-nrs score were significantly greater with roflumilast 0.3% vs vehicle at all timepoints (p≤0.034), and significantly greater with roflumilast 0.15% vs vehicle at weeks 6 and 12 (p≤0.012; figure 3) figure 3. proportion of patients with a wi-nrs score ≥6 at baseline who achieved a ≥4-point reduction from baseline in wi-nrs score wi-nrs assessed the worst itch over the past 24 hours on a scale ranging from 0 (no itch) to 10 (worst imaginable itch). data are presented for intent-to-treat population. missing data imputed using linear interpolation and last observation carried forward where linear interpolation was not computationally possible. wi-nrs: worst itch numeric rating scale. • robust improvements in severity of itch based on item 1 of the psd were observed for both roflumilast 0.3% and 0.15% at weeks 2 through 12 (p≤0.012 vs vehicle; figure 4) figure 4. psd item 1: “how severe was your psoriasis-related itching over the past 24 hours?” data are presented for intent-to-treat population. missing data imputed using linear interpolation and last observation carried forward where linear interpolation was not computationally possible. ls: least squares; psd: psoriasis symptom diary. -4 -3 -2 -1 0 baseline week 2 week 4 week 6 week 8 week 12 ls m ea n ch an ge in ps d it em 1 * * * * * * * * * * *nominal p<0.05 vs vehicle assessed severity of itch on a scale from 0 (no itching) to 10 (as bad as you can imagine) • robust improvements in burden of itch based on item 2 of the psd were observed for both roflumilast 0.3% and 0.15% at weeks 2 through 12 (p≤0.012 vs vehicle; figure 5) -4 -3 -2 -1 0 baseline week 2 week 4 week 6 week 8 week 12 ls m ea n ch an ge in ps d it em 2 * * * * * * * * • improvements in the itch-related sleep loss score were significantly greater with both roflumilast doses vs vehicle at weeks 6 through 12 (p≤0.022; figure 6) -4 -3 -2 -1 0 baseline week 2 week 4 week 6 week 8 week 12 ls m ea n ch an ge in it ch -r el at ed sl ee p lo ss n rs s co re * * * * * * *nominal p<0.05 vs vehicle 0 20 40 60 80 week 2 week 4 week 6 week 8 week 12 pa ti en ts , % * * * * * * * roflumilast 0.15% (n=62) vehicle (n=64)roflumilast 0.3% (n=71) i m p r o v e m e n t i m p r o v e m e n t i m p r o v e m e n t figure 5. psd item 2: “how bothered were you by your psoriasis-related itching over the past 24 hours?” data are presented for intent-to-treat population. missing data imputed using linear interpolation and last observation carried forward where linear interpolation was not computationally possible. ls: least squares; psd: psoriasis symptom diary. *nominal p<0.05 vs vehicle assessed burden of itch on a scale from 0 (not bothered at all) to 10 (as bothered as you can imagine) figure 6. itch-related sleep loss nrs score: “how intense was your itch-related sleep loss over the past 24 hours?” data are presented for intent-to-treat population. missing data imputed using linear interpolation and last observation carried forward where linear interpolation was not computationally possible. ls: least squares; nrs: numeric rating scale. *nominal p<0.05 vs vehicle assessed on a scale from 0 (no itch-related sleep loss) to 10 (sleep loss as bad as it can be) roflumilast 0.3% (n=109) roflumilast 0.15% (n=113) vehicle (n=109) * * figure 1. study design bsa: body surface area; iga: investigator global assessment; nrs: numeric rating scale; qd: once daily; pasi: psoriasis area and severity index; psd: psoriasis symptom diary; wi-nrs: worst itch numeric rating scale. roflumilast cream 0.3% qd roflumilast cream 0.15% qd vehicle qd endpoints • primary: iga “clear or “almost clear” at week 6 • secondary: – iga “clear” or “almost clear” skin + ≥2-grade improvement – pasi-75 and pasi-90 – intertriginous-iga “clear” or “almost clear” skin + ≥2-grade improvement – wi-nrs – psd – itch-related sleep loss nrs • safety and tolerability 12 weeks ra nd om iz at io n 1:1:1 n=331 eligibility • diagnosis of at least mild plaque psoriasis • age ≥18 years • 2-20% bsa linda stein gold,1 mark g. lebwohl,2 kim a. papp,3 melinda j. gooderham,4 leon h. kircik,5 zoe d. draelos,6 steven e. kempers,7 david m. pariser,8 javier alonso-llamazares,9 darryl p. toth,10 kathleen smith,11 robert c. higham,11 lynn navale,11 howard welgus,11 david r. berk11 1henry ford medical center, detroit, mi, usa; 2icahn school of medicine at mount sinai, new york, ny, usa; 3probity medical research and k papp clinical research, waterloo, on, canada; 4skin centre for dermatology, probity medical research and queen’s university, peterborough, on, canada; 5icahn school of medicine at mount sinai, new york, ny, indiana medical center, indianapolis, in, physicians skin care, pllc, louisville, ky, and skin sciences, pllc, louisville, ky, usa; 6dermatology consulting services, high point, nc, usa; 7minnesota clinical study center, fridley, mn, usa; 8department of dermatology, eastern virginia medical school and virginia clinical research, inc., norfolk, va, usa; 9driven research llc, coral gables, fl, usa; 10xlr8 medical research, probity medical research, windsor, on, canada; 11arcutis biotherapeutics, inc., westlake village, ca, usa roflumilast 0.3% (n=109) roflumilast 0.15% (n=113) vehicle (n=109) i m p r o v e m e n t roflumilast 0.3% (n=109) roflumilast 0.15% (n=113) vehicle (n=109) i m p r o v e m e n t roflumilast 0.3% (n=109) roflumilast 0.15% (n=113) vehicle (n=109) scan qr code for a digital copy of this poster roflumilast cream (arq-151) improved itch severity and itch-related sleep loss in adults with chronic plaque psoriasis in a phase 2b study << /ascii85encodepages false /allowpsxobjects false /allowtransparency false /alwaysembed [ true ] /antialiascolorimages false /antialiasgrayimages false /antialiasmonoimages false 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/pdfxoutputintentprofile (u.s. web coated \050swop\051 v2) /pdfxregistryname (http://www.color.org) /pdfxsetbleedboxtomediabox false /pdfxtrapped /false /pdfxtrimboxtomediaboxoffset [ 0 0 0 0 ] /parsedsccomments true /parsedsccommentsfordocinfo true /parseiccprofilesincomments true /passthroughjpegimages true /preservecopypage true /preservedicmykvalues true /preserveepsinfo true /preserveflatness false /preservehalftoneinfo false /preserveopicomments false /preserveoverprintsettings true /startpage 1 /subsetfonts true /transferfunctioninfo /apply /ucrandbginfo /remove /useprologue false /srgbprofile (srgb iec61966-2.1) >> setdistillerparams << /hwresolution [2400 2400] /pagesize [612.000 792.000] >> setpagedevice references 1. karia ps et al. j am acad dermatol. 2013;68:957–966. 2. rogers hw et al. jama dermatol. 2015;151:1081–1086. 3. que sk et al. jaad. 2018;78:237–247. 4. ahmed sr et al. expert rev clin pharmacol. 2019;12:947–951. 5. migden mr et al. n engl j med. 2018;379:341–351. 6. rischin d et al. ann oncol. 2019;30(suppl 5):536–537. 7. migden mr et al. j clin oncol. 2019;37(15 suppl):6015. 8. migden mr et al. lancet oncol. 2020;21:294–305. 9. aaronson nk et al. j natl cancer inst. 1993;85:365–376. 10. mills kc et al. arch dermatol. 2012;148:1422–1423. 11. osoba d et al. j clin oncol. 1998;16:139–144. 12. scott nw et al. eortc qlq-c30 reference values. 2nd ed. brussels, belgium: eortc quality of life group. 2008. available at: www.eortc.org/ app/uploads/sites/2/2018/02/reference_values_manual2008.pdf. [accessed may 1, 2020]. funding sources funding was provided by regeneron pharmaceuticals, inc. and sanofi. acknowledgments the authors would like to thank the patients, their families, all other investigators, and all investigational site members involved in this study. the study was funded by regeneron pharmaceuticals, inc. and sanofi. medical writing support was provided by e. jay bienen, phd, and typesetting was provided by kate carolan, phd, of prime, knutsford, uk, funded by regeneron pharmaceuticals, inc. and sanofi. for any questions or comments, please contact dr michael r migden, mrmigden@mdanderson.org disclosures m. r. migden reports honoraria and travel expenses from regeneron pharmaceuticals, inc., sanofi, novartis, genentech, eli lilly, and sun pharma; and institutional research funding from regeneron pharmaceuticals, inc., novartis, genentech, and eli lilly. d. rischin reports institutional research grant and funding from regeneron pharmaceuticals, inc., roche, merck sharp & dohme, bristol-myers squibb, and glaxosmithkline; uncompensated scientific committee and advisory board from merck sharp & dohme, regeneron pharmaceuticals, inc., sanofi, glaxosmithkline, and bristol-myers squibb; travel and accommodation from merck sharp & dohme and glaxosmithkline. a. pavlick reports honoraria and consulting or advisory roles at bristol-myers squibb, merck, regeneron pharmaceuticals, inc., array, novartis, seattle genetics, and amgen; research funding from bristol-myers squibb, merck, regeneron pharmaceuticals, inc., celldex, and forance; travel, accommodation, and expenses from regeneron pharmaceuticals, inc., array, and seattle genetics. c.d. schmults is a steering committee member for castle biosciences; a steering committee member and consultant for regeneron pharmaceuticals, inc.; a consultant for sanofi; has received research funding from castle biosciences, regeneron pharmaceuticals, inc., novartis, genentech, and merck, and is a chair for the national comprehensive cancer network. a. guminski reports personal fees and non-financial support (advisory board and travel support) from bristol-myers squibb and sun pharma; personal fees (advisory board) from merck kgaa, eisai, and pfizer; non-financial (travel) support from astellas; and clinical trial unit support from ppd australia. a. hauschild reports institutional grants, speaker’s honoraria, and consultancy fees from amgen, bristol-myers squibb, merck sharp & dohme/merck, pierre fabre, provectus, roche, and novartis; institutional grants and consultancy fees from merck serono, philogen, and regeneron pharmaceuticals, inc.; and consultancy fees from oncosec. a.l.s. chang reports consulting and advisory roles at regeneron pharmaceuticals, inc. and merck; research funding from regeneron pharmaceuticals, inc., novartis, galderma, and merck. g. rabinowits reports consulting and advisory roles for emd serono pfizer, sanofi, regeneron pharmaceuticals inc., merck and castle, and stock/other ownership interests from syros pharmaceuticals and regeneron pharmaceuticals, inc. s. ibrahim reports research funding from regeneron pharmaceuticals, inc. and castle, speakers’ bureau from genentech, and travel and accommodation expenses from regeneron pharmaceuticals, inc. and genentech. m. sasane, v. mastey, z. chen, d. bury, i. lowy, m.g. fury, s. li, and c-i chen are employees and shareholders of regeneron pharmaceuticals, inc. summary and conclusion • in advanced cscc patients, treatment with cemiplimab resulted in clinically meaningful reduction in pain as early as cycle 3 with maintenance of effect through cycle 12. • improvement in global health status/hrql was observed as early as cycle 3 with clinically meaningful improvement seen by cycle 12. • by cycle 6, the majority of patients experienced clinically meaningful improvement or stability in global health status/hrql and functional status, while maintaining a low symptom burden. • these results further support cemiplimab as a new standard of care option in the treatment of advanced cscc. synopsis • cutaneous squamous cell carcinoma (cscc) is considered the second most common malignancy in the us, although its exclusion from national cancer registries has presented a barrier to epidemiologic characterization.1 estimates suggest an incidence of around 1.5 million cases per year in the us.2 the incidence of cscc is increasing yearly in the us.3 • most cscc patients have a favorable prognosis, but for the patients who are not amenable to curative surgery, palliative systemic therapy has been administered.1 • cemiplimab is a programmed cell death (pd)-1 inhibitor that is indicated for treatment of cscc in patients with metastatic (mcscc) or locally advanced (lacscc) disease not amenable to curative surgery or curative radiation.4 cemiplimab demonstrated a robust durable clinical response and a safety profile consistent with other checkpoint inhibitors in a recent phase 2 study (nct02760498).5–8 longer follow-up data from the phase 2 study of cemiplimab in patients with advanced cscc is presented in the poster titled “phase 2 study of cemiplimab in patients with advanced cutaneous squamous cell carcinoma (cscc): longer follow-up”, also available on the 2020 fall clinical dermatology conference platform. no new safety signals emerged with longer follow-up. the most common treatment-emergent adverse events of any grade were fatigue (n=67, 34.7%), diarrhea (n=53, 27.5%), and nausea (n=46, 23.8%). • the phase 2 trial included the european organisation for research and treatment of cancer (eortc) cancer-specific 30-item questionnaire (qlq-c30)9 as a measure of patient-reported health-related quality of life (hrql). • pain is an important and bothersome symptom in the diagnosis and treatment of cscc from the patient and clinical perspectives.10 objective • this post hoc exploratory analysis examined the qlq-c30 data from a phase 2 clinical trial (nct02760498) to determine the effects of cemiplimab treatment on hrql and pain. methods • for inclusion in the phase 2, non-randomized, global, pivotal trial of cemiplimab (figure 1), adults with invasive cscc not amenable to curative surgery or curative radiotherapy according to the investigator were also required to have ≥1 lesion, eastern cooperative oncology group (ecog) performance status ≤1, and life expectancy >12 weeks. adult patients (n=193) received intravenous (iv) cemiplimab 3 mg/kg every 2 weeks (q2w; mcscc n=59; lacscc n=78) for 12 treatment cycles or 350 mg every 3 weeks (q3w; mcscc n=56) for six treatment cycles. treatment cycle length was 8 weeks for groups 1 and 2 and 9 weeks for group 3. the primary efficacy endpoint was objective response rate, defined as the proportion of patients with complete or partial response. • at baseline and day 1 of each treatment cycle until progression, patients were administered the qlq-c30.9 group 1 – adult patients with metastatic (nodal and/or distant) cscc cemiplimab 3 mg/kg q2w iv, for up to 96 weeks cemiplimab 350 mg/kg q3w iv, for up to 54 weeks tumor response assessment by icr (recist v1.1 for scans; modified who criteria for photos) eortc qlq-c30 quality of life questionnaire administered at baseline and day 1 of each treatment cycle tumor imaging every 8 weeks for the assessment of clinical activity tumor imaging every 9 weeks for the assessment of clinical activity group 3 – adult patients with metastatic (nodal and/or distant) cscc group 2 – lacscc key inclusion criteria • ecog performance status of 0 or 1 • adequate organ function • groups 1 and 3: at least one lesion measurable by recist v1.1 • group 2 at least one lesion measurable by digital medical photography cscc lesion that is not amendable to curative surgery or curative radiation therapy per investigators’ assessment tumor biopsies at baseline and on day 29, for exploratory biomarker analysis, unless considered to have unacceptable safety risks by the investigator key exclusion criteria • ongoing or recent (within 5 years) autoimmune disease requiring systemic immunosuppression • prior treatments with anti–pd-1 or anti–pd-l1 therapy • history of solid organ transplant, concurrent malignancies (unless indolent or not considered life-threatening; for example, basal cell carcinoma), or hematologic malignancies figure 1. study design icr, independent central review; pd-l1, pd-ligand 1; recist v1.1, response evaluation criteria in solid tumors version 1.1; who, world health organization. 29.8 (30.4) 20.3 (26.9) 13.6 (20.2) 16.0 (23.0) 12.7 (19.5) 14.9 (22.8) 12.5 (21.9) 9.4 (17.6) 12.8 (23.3) 12.7 (22.4) 8.3 (18.2) 12.4 (20.9) 65.1 (22.9) 70.1 (21.6) 75.4 (19.7) 75.8 (19.0) 75.3 (18.4) 73.4 (21.2) 75.1 (21.0) 77.4 (18.5) 75.8 (19.5) 77.8 (16.6) 78.2 (18.8) 77.1 (19.9) 100 80 60 40 20 0 100 80 60 40 20 0 baseline 2 3 4 5 6 7 8 9 10 11 12 150 136 122 104 104 101 84 73 65 59 52 43 152 137 125 105 105 101 84 73 65 59 52 43 m e a n p a in s c o re ( s d ); lo w e r sc o re = b e tt e r o u tc o m e n = n = cycle (day 1) m e a n g lo b a l h e a lth sta tu s/h r q l sc o re (s d ); h ig h e r sc o re = b e tte r o u tc o m e figure 2. qlq-c30 pain and global health status/hrql scores by cycle 23 14 30 40 35 14 56 16 44 47 23 28 28 30 51 60 77 60 53 60 72 28 79 30 30 58 58 49 56 40 16 9 9 7 5 14 16 5 26 23 19 14 23 14 9 improvement maintenance deterioration cycle 12 (n=43) 13 7 22 28 31 19 43 11 37 35 23 26 28 23 43 75 88 64 62 51 71 41 78 31 49 55 59 40 56 40 12 5 14 10 18 10 17 11 33 17 22 15 33 21 18 0 20 40 60 80 100 global health status/hrql physical function role function emotional function cognitive function social function fatigue nausea/vomiting pain dyspnea insomnia appetite loss constipation diarrhea financial problems patients (%) 0 20 40 60 80 100 patients (%) cycle 6 (n=101) figure 3. proportion of patients reporting clinically meaningful change at cycle 6 and cycle 12 health-related quality of life (hrql) in patients with advanced cutaneous squamous cell carcinoma (cscc) treated with cemiplimab: post hoc exploratory analysis of a phase 2 clinical trial michael r. migden,1 danny rischin,2 medha sasane,3 vera mastey,4 anna pavlick,5 chrysalyne d. schmults,6 zhen chen,4 alexander guminski,7 axel hauschild,8 denise bury,9 anne lynn s. chang,10 guilherme rabinowits,11 sherrif ibrahim,12 israel lowy,4 matthew g. fury,4 siyu li,13 chieh-i chen4 1departments of dermatology and head and neck surgery, university of texas md anderson cancer center, houston, tx, usa; 2department of medical oncology, peter maccallum cancer centre, melbourne, australia; 3sanofi, bridgewater, nj, usa; 4regeneron pharmaceuticals, inc., tarrytown, ny, usa; 5department of medical oncology, new york university langone medical center, new york, ny, usa; 6department of dermatology, brigham and women’s hospital, harvard medical school, boston, ma, usa; 7department of medical oncology, royal north shore hospital, st leonards, australia; 8department of dermatology, university hospital (uksh), kiel, germany; 9sanofi, cambridge, ma, usa 10department of dermatology, stanford university school of medicine, ca, usa; 11department of hematology/oncology, miami cancer institute/baptist health south florida, miami, fl, usa; 12department of dermatology, rochester medical center, rochester, ny, usa; 13regeneron pharmaceuticals, inc., basking ridge, nj, usa table 1. demographic and clinical characteristics of the full analysis set variable total (n=193) mcscc 350 mg q3w (n=56) mcscc 3 mg/kg q2w (n=59) lacscc 3 mg/kg q2w (n=78) age, mean ± sd, years 71.1 ± 11.4 69.7 ± 12.8 70.4 ± 10.1 72.5 ± 11.2 ≥65 years, n (%) 144 (74.6) 42 (75.0) 43 (72.9) 59 (75.6) male, n (%) 161 (83.4) 48 (85.7) 54 (91.5) 59 (75.6) ecog performance status, n (%) 0 86 (44.6) 25 (44.6) 23 (39.0) 38 (48.7) 1 107 (55.4) 31 (55.4) 36 (61.0) 40 (51.3) primary site, n (%) head and neck 131 (67.9) 31 (55.4) 38 (64.4) 62 (79.5) other 62 (32.1) 25 (44.6) 21 (35.6) 16 (20.5) prior cancer-related systemic therapy, n (%) 65 (33.7) 20 (35.7) 33 (55.9) 12 (15.4) prior cancer-related radiotherapy, n (%) 131 (67.9) 38 (67.9) 50 (84.7) 43 (55.1) sd, standard deviation. table 2. baseline scores and change from baseline (mmrm) in patients in the full analysis set who had baseline and post-baseline assessments on each qlq-c30 scale or item qlq-c30 scale/item baseline, mean ± sd (n) ls mean change ± se (n) cycle 3 cycle 12 global health status/hrql 65.1 ± 22.9 (150) 7.8 ± 1.6 (122)** 11.1 ± 2.6 (43)** functional scales† physical function 80.1 ± 22.8 (151) 1.1 ± 1.3 (124) 4.0 ± 2.1 (43) role function 75.8 ± 30.0 (151) 0.4 ± 2.1 (123) 5.6 ± 3.4 (43) emotional function 80.2 ± 21.2 (151) 4.2 ± 1.3 (123)* 5.3 ± 2.2 (43)* cognitive function 83.4 ± 22.2 (151) 1.7 ± 1.4 (123) 2.5 ± 2.3 (43) social function 74.4 ± 31.8 (150) 5.3 ± 1.8 (122)* 8.6 ± 3.0 (43)* symptoms‡ fatigue 30.2 ± 24.6 (152) –2.8 ± 1.7 (125) –4.8 ± 2.8 (43) nausea/vomiting 4.6 ± 12.2 (152) –1.6 ± 0.8 (125)* –2.9 ± 1.3 (43)* pain 29.8 ± 30.4 (152) –11.5 ± 1.9 (125)** –14.3 ± 3.1 (43)** dyspnea 12.9 ± 23.4 (152) 0.7 ± 1.7 (125) 1.5 ± 2.9 (43) insomnia 27.4 ± 28.0 (151) –9.1 ± 2.0 (123)** –17.4 ± 3.3 (43)** appetite loss 19.5 ± 29.3 (152) –8.4 ± 1.6 (124)** –13.7 ± 2.7 (43)** constipation 13.6 ± 24.1 (152) –4.5 ± 1.5 (125)* –11.2 ± 2.5 (43)** diarrhea 4.9 ± 13.6 (150) 3.6 ± 1.4 (121)* 0.6 ± 2.3 (43) financial difficulty 19.1 ± 30.7 (150) 0.5 ± 2.0 (122) –3.4 ± 3.3 (43) **p<0.001 and *p<0.05 versus baseline. †higher scores reflect better outcomes. ‡lower scores reflect better outcomes. • the qlq-c30 assesses hrql over the past week among cancer patient populations using a global health status/hrql scale, five functional scales, and nine symptom scales/items. functional scales include physical, role, cognitive, emotional, and social functioning. symptom scales/items include fatigue, pain, nausea/vomiting, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties. scores range from 0 to 100; high scores on functional scales and low scores on symptom scales reflect better outcomes. a change ≥10 points from baseline is considered clinically meaningful.11 • the full analysis set included patients who had baseline and at least one post-baseline assessment for any qlq-c30 scale. • descriptive statistics were used to summarize hrql scores over time (only pain and global health status/hrql scores are shown). • mixed effects repeated measures models (mmrm) were used to estimate the mean treatment effect (change from baseline while accounting for missing data) for all qlq-c30 scales. the model included fixed effects of treatment, visit, treatment-by-visit interaction, and baseline value of the specified individual item. results are expressed as the least squares (ls) mean and standard error (se). • a responder analysis was also conducted at cycle 6 and cycle 12 based on evaluation of average change from baseline among patients who had baseline scores that allowed a ≥10-point change. a responder was defined as a patient who achieved an average 10-point increase in functional scale scores and 10-point decline in symptom scale scores. results patient population and baseline scores • a total of 193 adult patients were enrolled in the study, and demographic characteristics were generally similar across the treatment groups (table 1). • baseline scores for qlq-c30 indicated generally moderate to high levels of functioning and moderate to low symptom burden (table 2). pain is of importance as a symptom in patients with advanced cscc, and the baseline pain score of patients with advanced cscc receiving cemiplimab (29.8 ± 30.4) was worse than that reported by patients with advanced head and neck cancer (24.9 ± 26.3; n=1722) and the general population (20.9 ± 27.6; n=7802) in the literature12; comparisons with both groups were significant, p<0.05 and p<0.0001, respectively. longitudinal analysis • among the symptom scales and items, a marked improvement in pain score was observed as early as cycle 2 (figure 2). the initial clinically meaningful improvement (≥10 points) in pain score at cycle 3 (ls mean [se] change –11.5 [1.9]; p<0.0001) was maintained during study treatment to cycle 12 (ls mean [se] change –14.3 [3.1]; p<0.0001) (table 2). at cycle 3, significant improvements from baseline were also observed for symptoms of insomnia, appetite loss, and constipation. at cycle 12, these improvements reached the clinically meaningful threshold (table 2). with the exception of a significant worsening of diarrhea at cycle 3 and a significant improvement of nausea/vomiting at cycle 12, all other domains/symptoms remained stable relative to baseline. by cycle 12, diarrhea remained stable relative to baseline. • among the functional scales, significant improvements were observed in emotional and social function at cycle 3 and cycle 12. all other functional scales remained stable relative to baseline (table 2). • for global health status/hrql, significant improvement from baseline was observed at cycle 3. at cycle 12, this improvement reached the clinically meaningful threshold (ls mean [se] change 11.1 [2.6]; p<0.0001) (table 2). responder analysis • by cycle 6, the majority of patients experienced clinically meaningful (≥10 points) improvement or stability including pain (83%), nausea/vomiting (89%), diarrhea (95%), constipation (86%), and appetite loss (90%), as well as functional scales (77%–86%) (figure 3). these effects likely account for the clinically meaningful improvement or stability also reported on global health status/hrql among the majority of patients (82%). • at cycle 12, the majority of patients showed sustained improvement and stabilization across all symptoms and functional scales (74%–95%). ninetyone percent of patients experienced clinically meaningful improvement or stability in global health status/hrql scores at cycle 12 (figure 3). • the proportions of patients with clinically meaningful deterioration were generally low at both evaluated time points (figure 3). the highest rate of clinically relevant deterioration among the symptoms was observed for fatigue. study limitations • this was a non-randomized, single-arm, open-label study. • the 10-point threshold considered indicative of a clinically meaningful change has not been validated for this specific patient population (i.e., advanced cscc). presented at the 2020 fall clinical dermatology conference, october 29–november 1, virtual scientific meeting (encore of asco 2020 poster presentation). skin may 2019 volume 3 issue 3 copyright 2018 the national society for cutaneous medicine 180 in-depth reviews a review of treatments for dissecting cellulitis of the scalp andrew x. tran bs1, rebecca m. sarac bs1, lisa prussick bs, ms2, stella m. radosta ba, ms1, andrea murina md1* atulane university school of medicine, department of dermatology new orleans, la btufts university school of medicine, department of dermatology, boston, massachusetts the main features of dissecting cellulitis of the scalp (dcs) are pustules, suppurative nodules, draining sinuses, and scars. it can be associated with acne conglobata, hidradenitis suppurativa, and pilonidal cysts which are collectively referred to as the follicular occlusion tetrad12. although these diseases are specific to different body sites, they are characterized by follicular-based inflammation that leads to tissue scarring. the pathogenesis of dcs is unknown, although it is speculated to be related to follicular occlusion that is secondary to an infection3. however, a specific pathogenic bacterium has yet to be determined4. dcs is also classified as a primary cicatricial alopecia, where the hair follicles are irreparably destroyed and replaced by fibrous tissue5. patients with dissecting cellulitis may experience psychological distress as a result of the alopecia and scarring. dcs has a higher prevalence in african american males between the ages of 20-406, although there have been reports of this condition occurring in women7 and men of other ethnic origins8, 9. histologically, there are abscesses, inflammatory infiltrates of neutrophils, dermal fibrosis, and decreased introduction dissecting cellulitis of the scalp (dcs) is a rare and chronic skin disorder that presents with suppurative nodules on the scalp with associated scarring alopecia. the pathogenesis of the disease involves inflammation and destruction of the hair follicle. this makes it clinically and pathologically similar to acne conglobata and hidradenitis suppurativa, which can also occur concomitantly. many therapies exist to treat dcs, but its refractory nature makes treatment difficult and combination therapies are often needed. the aim of this review is to evaluate the evidence-based medical and surgical treatments for this disease so that clinicians can choose the best treatments according to the disease stage and severity. knowledge of the clinical endpoints of each treatment modality is important for managing patient expectations and setting treatment goals. there is no standardized method for measurement of clinical improvement in dcs, and each individual treatment can improve one or more aspect of disease activity (such as inflammation or scarring). topical and oral medications will be reviewed in addition to surgical and laser treatments. abstract skin may 2019 volume 3 issue 3 copyright 2018 the national society for cutaneous medicine 181 density of hair follicles10. culture of the exudate may reveal the presence of bacteria that is secondary to the follicular occlusion, most commonly staphylococcal species10. dcs is characterized by the absence of fungi, as tinea capitis can be a mimicker11. treatment of dcs varies greatly based on the severity of disease. a patient with early stage disease will likely benefit from treatments that are directed against bacterial colonization and inflammation such as oral and topical antibiotics, retinoids, and biologics. later stage disease requires treatments that address the end-stage scarring and alopecia associated with the disease. these treatments can include intralesional steroids to decrease scar, excision or marsupialization of the diseased skin, or laser treatments to target the hair. early and late inflammatory stages of dcs are illustrated in figure 1 and figure 2. antibiotics oral antibiotics have demonstrated success in dissecting cellulitis and are appropriate agents for patients with early limited disease. oral antibiotics are used for their quick action and anti-inflammatory effect, however relapses can occur when stopped. a retrospective review of 40 patients with dcs showed clinical improvement while on oral antibiotics such as doxycycline, pristinamycin, rifampicin, or a combination of several antibiotics, however all patients relapsed when discontinuing the medication12. a retrospective review of 21 patients with biopsy-proven dcs reported positive outcomes with doxycycline, azithromycin, or a combination rifampicin and clindamycin13. two case studies demonstrated complete resolution with figure 1. early inflammatory stage dissecting cellulitis with sinus tracts and alopecia. oral antibiotics in combination with adalimumab and intralesional steroids were used in this patient. figure 2. late stage dissecting cellulitis with significant scarring alopecia. oral antibiotics and intralesional steroids were used to treat this patient. ciprofloxacin for 1 month with treatmentrefractory dcs14, 15. oral clindamycin in combination with topical clobetasol was also successful at improving disease burden in a series of three patients17. these findings are summarized in table 1. treatments skin may 2019 volume 3 issue 3 copyright 2018 the national society for cutaneous medicine 182 table 1. treatment of dcs with antibiotics. author reference study design method number of patients treatment duration disease symptom improvements (yes/no) hair regrowth? (yes/no) seguradomiravalles et al. 2017 retrospective review doxycycline 100 mg q.d. 5 n/a yes, 4 of 5 patients n/a azithromycin 500 mg q.d. three times a week 3 n/a yes n/a rifampicin 300 mg b.i.d. and clindamycin 300 mg b.i.d. 1 10 weeks yes n/a garelli et al. 2017 case series clindamycin 300 mg b.i.d. 4 1 month yes n/a badaoui et al. 2016 retrospective review doxycycline, pristinamycin, rifampicin, or combination of antibiotics 40 11 months yes, but relapse reported after treatment discontinuation n/a onderdijk and boer 2010 case report ciprofloxacin 500 mg b.i.d. for 1 month then 250 mg b.i.d. for 3 weeks 1 5 months yes n/a greenblatt et al. 2008 case report ciprofloxacin 250 mg b.i.d. for 1 month then 250 q.d. for 4 months 1 5 months yes yes salim et al. 2003 case report trimethoprim 100 mg b.i.d. and clindamycin aqueous solution 1 18 months yes n/a table 2. treatment of dcs with retinoids. author reference study design method number of patients treatment duration disease symptom improvements (yes/no) hair regrowth? (yes/no) seguradomiravalles et al. 2017 retrospective study isotretinoin 30 mg q.d. 8 n/a yes, 7 of 8 patients n/a marquis et al. 2017 case report isotretinoin 20 mg q.d. 1 4 months yes yes badaoui et al. 2016 retrospective review isotretinoin 0.50.8 mg/kg q.d. 35 6 months yes, 33 of 35 patients but relapse reported after treatment discontinuation n/a acitretin 30 mg q.d. 1 11 months n/a n/a jacobs et al. 2011 case report acitretin 10 mg q.d. 1 6 months yes n/a skin may 2019 volume 3 issue 3 copyright 2018 the national society for cutaneous medicine 183 georgala et al. 2008 case series isotretinoin 0.5 mg/kg q.d. for 34 months 4 7 – 8 months yes n/a bolz et al. 2008 case report isotretinoin 80 mg q.d for 4 weeks then with dapsone 50 mg b.i.d. for 10 months 1 12 months yes yes khaled et al. 2007 case report isotretinoin 0.8 mg/kg q.d. 1 12 months yes yes shaffer et al. 1992 case report triamcinolone acetonide (40 mg/ml) intralesional injections and isotretinoin 0.85 1.48 mg/kg over x 5 months 1 5 months yes yes table 3. treatment of dcs with biologic agents. author reference study design method number of patients treatment duration disease symptom improvements (yes/no) hair regrowth? (yes/no) badaoui et al. 2016 retrospective review infliximab 1 11 months no n/a mansouri et al. 2016 case report adalimumab 80 mg on day 0, 40 mg on day 7, and 40 mg every other week thereafter 1 5 months yes n/a infliximab 5 mg/kg at week 0, 2 and 6, followed by 8 week intervals 1 20 months yes n/a wollina et al. 2012 case report infliximab 5 mg/kg body weight at weeks 0, 2, and 6 1 6 weeks yes n/a navarini and trüeb 2010 case series adalimumab 80 mg followed by 40 mg 1 week after and an additional 40 mg every 2 weeks 3 1 – 7 years yes, but relapse reported within 4 weeks after treatment discontinuation n/a skin may 2019 volume 3 issue 3 copyright 2018 the national society for cutaneous medicine 184 table 4. procedural therapies. procedure authors study design method time of followup dcs recurrence? (yes/no) hair regrowth? (yes/no) surgical excision housewright et al. 2011 case report scalpectomy with split thickness skin graft 10 months no no bellew et al. 2003 case report 2 months no no williams et al. 1986 case report 1 – 4 years no no badaoui et al. 2016 retrospective study surgical treatment (excision or abscess drainage) n/a n/a n/a meunier et al. 2014 case report marsupialization 7 months no no laser-assisted epilation krasner et al. 2006 observational nd:yag laser 1 year no yes, 3 of 4 patients boyd and binhlam 2002 case report 800-nm longpulsed diode laser 6 months no no photodynamic therapy (pdt) liu et al. 2013 case report ala pdt 5 months no no x-ray epilation mcmullan and zeligman 1956 case series x-ray 6 months – 1 year no yes skin may 2019 volume 3 issue 3 copyright 2018 the national society for cutaneous medicine 185 combination therapy with corticosteroids oral, intralesional or topical corticosteroids can be used in dcs to reduce inflammation and swelling of the scalp, and to minimize scarring. monotherapy with oral corticosteroids is not recommended due to the risk of relapse and long-term side effects. salim et al. reported a case of a man with dcs and spondylarthropathy who noted improvement with prednisolone 30mg daily but relapsed when the prednisolone was tapered19 intralesional triamcinolone and topical steroids can be used alone in patients with limited disease or in combination with systemic treatments. these combination treatments are included in table 2. topical corticosteroids have not been studied as monotherapy in dcs. retinoids isotretinoin and acitretin are used for the treatment of dcs because they reduce follicular occlusion and decrease sebaceous activity. isotretinoin can offer good results, particularly when used early in the disease course, because of the possibility of remission within one year of therapy21-24. patients in a case report and comprehensive review were able to achieve remission on monotherapy with isotretinoin doses from 0.5-1 mg/kg over 4-12 months21, 23, although one case report added dapsone for sustained improvement22. one case report of a 25-yearold man was administered 0.8 mg/kg isotretinoin and achieved significant clinical improvement within 4 months of treatment, with evidence of hair regrowth at 6 months. he was also able to discontinue isotretinoin after 12 months with sustained remission 6 months later21. shaffer et al. reported successful resolution of dcs in a patient treated with a combination of 5 months of isotretinoin and bimonthly intralesional triamcinolone injections18. a retrospective study conducted at two dermatology departments in france between 1996-2013 found similar efficacy, with 92% of patients treated with isotretinoin 0.5-0.8 mg/kg achieving remission within 3 months of therapy. however, their data found frequent relapse upon discontinuation, suggesting that longer courses may be required for sustained remission12. acitretin can be used for patients requiring long-term systemic therapy as well. jacobs et al., reported a patient treated with prednisolone, topical corticosteroids, topical tacrolimus, and acitretin. the systemic and topical steroids were tapered, and the patient remained stable on acitretin six months later20. retinoids can be considered as monotherapy in early disease or in combination with other systemic and topical agents in later stage disease. it is important to consider the use of isotretinoin early in the disease course in order to attempt to stop further structural damage to the hair follicle. these findings are summarized in table 2. biologics tumor necrosis factor (tnf) inhibitors have been used in dcs due to its similar pathogenesis to hidradenitis suppurativa. tnf inhibition is effective for suppression of the inflammation of dcs, but studies show that it does not reverse fibrosis. a case series by navarini and trueb demonstrated significant symptomatic improvement on adalimumab in three patients with severe clinical disease who had failed isotretinoin therapy25. these patients were subcutaneously administered 80mg at week 0, 40mg at week 1, and 40mg every 2 weeks thereafter. subjective burden of disease was significantly reduced in all three patients at 8 weeks of treatment, however, relapse skin may 2019 volume 3 issue 3 copyright 2018 the national society for cutaneous medicine 186 occurred within 4 weeks of discontinuing therapy25. other case reports using adalimumab have found similar clinical improvement and reduction in dermatology life quality index (dlqi) with this dosing regimen26, 27. higher doses may provide additional efficacy, but no studies have been reported using a weekly dosing regimen. infliximab may also provide similar improvement to adalimumab. in a recent case report, a patient with a severe suppurative dcs had reduced symptoms and inflammation on infliximab (5 mg/kg at weeks 0, 2, and 6, with 8-week intervals thereafter), but did not have reversal of the fibrosis associated with dcs26. tnf inhibitors like adalimumab and infliximab are useful treatment options for patients with moderate to severe disease with prominent nodules, abscesses and sinus tracts 25. patients with prominent scarring will likely require combination with other treatments such as intralesional corticosteroids or procedural therapies. these findings are summarized in table 3. procedural therapies for intractable cases of dcs, procedural therapies including x-ray epilation, surgical excision, laser treatment and photodynamic therapy have been reported. x-ray therapy is no longer a primary treatment option due to increased risk of skin cancer28. surgical procedures that have shown benefit in the treatment of dcs include scalpectomy (excision of the diseased scalp skin) and marsupialization. treatment with scalpectomy was first reported in 1986 with subsequent publication of successful cases6, 29, 30. more recently, marsupialization was shown to be of benefit in dcs as it is significantly less invasive and can heal remarkably well by secondary intention without the requirement for split-thickness grafting31. however, new lesions can occur in untreated areas and in all reported surgical modalities, hair regrowth was never observed29-31. in patients with longstanding disease and significant scarring, surgical options can be discussed early to provide a targeted reduction in disease burden. recently, hair follicle ablation with laser treatment has been successfully reported in regard to achieving long-term remission of dcs and can also stimulate hair regrowth. in one case series, four patients were treated with three to seven monthly treatments over one year with the 1,064-nm nd:yag laser. three patients had at least partial hair regrowth at treatment sites32. the use of 5aminolevulinic acid photodynamic therapy (ala-pdt) has been reported to be successful in one case with no recurrent disease at 5 months follow up. laser and light therapies may be preferential to surgery for patients who have failed multiple conventional therapies and seek to retain hair and may be combined with systemic and topical treatments. these findings are summarized in table 4. the multitude of treatment options for dcs reflects the refractory nature of this chronic skin condition. this makes dcs challenging to treat and places a substantial burden on the quality of life of those afflicted. due to the progressive nature of the disease, establishing the diagnosis early and providing directed treatments will lead to the best patient outcomes. treatment selection should account for disease severity and the amount of abscesses, sinus tracts and scar. combination treatments with both medical and surgical modalities may offer patients discussion skin may 2019 volume 3 issue 3 copyright 2018 the national society for cutaneous medicine 187 with dcs the best results to address both the inflammatory and fibrotic processes of this disease. conflict of interest disclosures: dr. murina is a speaker for abbvie, celgene, janssen and novartis funding: none. corresponding author: andrea murina, md department of dermatology tulane university school of medicine new orleans, la amurina@tulane.edu references: 1. chicarilli, z. n., follicular occlusion triad: hidradenitis suppurativa, acne conglobata, and dissecting cellulitis of the scalp. ann plast surg 1987, 18 (3), 230-7. 2. plewig, g.; kligman, a., in acne: morphogenesis and treatment, springer-verlag: berlin, 1975; pp 1923. 3. mundi, j. p.; marmon, s.; fischer, m.; kamino, h.; patel, r.; shapiro, j., dissecting cellulitis of the scalp. dermatol online j 2012, 18 (12), 8. 4. lebwohl, m., treatment of skin disease : comprehensive therapeutic strategies. 3rd ed. ed.; saunders: [edinburgh?], 2010. 5. rigopoulos, d.; stamatios, g.; ioannides, d., primary scarring alopecias. curr probl dermatol 2015, 47, 76-86. 6. williams, c. n.; cohen, m.; ronan, s. g.; lewandowski, c. a., dissecting cellulitis of the scalp. plast reconstr surg 1986, 77 (3), 378-82. 7. goldsmith, p. c.; dowd, p. m., successful therapy of the follicular occlusion triad in a young woman with high dose oral antiandrogens and minocycline. j r soc med 1993, 86 (12), 729-30. 8. koca, r.; altinyazar, h. c.; ozen, o. i.; tekin, n. s., dissecting cellulitis in a white male: response to isotretinoin. int j dermatol 2002, 41 (8), 509-13. 9. lim, d. t.; james, n. m.; hassan, s.; khan, m. a., spondyloarthritis associated with acne conglobata, hidradenitis suppurativa and dissecting cellulitis of the scalp: a review with illustrative cases. curr rheumatol rep 2013, 15 (8), 346. 10. lee cn, chen w, hsu ck, weng tt, lee jy, yang cc. dissecting folliculitis (dissecting cellulitis) of the scalp: a 66patient case series and proposal ofclassification. j dtsch dermatol ges. 2018 oct;16(10):1219-1226. 11. stein, l. l.; adams, e. g.; holcomb, k. z., inflammatory tinea capitis mimicking dissecting cellulitis in a postpubertal male: a case report and review of the literature. mycoses 2013, 56 (5), 596600. 12. badaoui, a.; reygagne, p.; cavelierballoy, b.; pinquier, l.; deschamps, l.; crickx, b.; descamps, v., dissecting cellulitis of the scalp: a retrospective study of 51 patients and review of literature. br j dermatol 2016, 174 (2), 421-3. 13. segurado-miravalles, g.; camachomartínez, f. m.; arias-santiago, s.; serrano-falcón, c.; serrano-ortega, s.; rodrigues-barata, r.; jaén olasolo, p.; vañó-galván, s., epidemiology, clinical presentation and therapeutic approach in a multicentre series of dissecting cellulitis of the scalp. j eur acad dermatol venereol 2017, 31 (4), e199e200. 14. greenblatt, d. t.; sheth, n.; teixeira, f., dissecting cellulitis of the scalp mailto:amurina@tulane.edu skin may 2019 volume 3 issue 3 copyright 2018 the national society for cutaneous medicine 188 responding to oral quinolones. clin exp dermatol 2008, 33 (1), 99-100. 15. onderdijk, a. j.; boer, j., successful treatment of dissecting cellulitis with ciprofloxacin. clin exp dermatol 2010, 35 (4), 440. 16. georgala, s.; korfitis, c.; ioannidou, d.; alestas, t.; kylafis, g.; georgala, c., dissecting cellulitis of the scalp treated with rifampicin and isotretinoin: case reports. cutis 2008, 82 (3), 195-8. 17. garelli, v.; didona, d.; paolino, g.; didona, b.; calvieri, s.; rossi, a., dissecting cellulitis: responding to topical steroid and oral clindamycin. g ital dermatol venereol 2017, 152 (3), 324-325. 18. shaffer, n.; billick, r. c.; srolovitz, h., perifolliculitis capitis abscedens et suffodiens. resolution with combination therapy. arch dermatol 1992, 128 (10), 1329-31. 19. salim, a.; david, j.; holder, j., dissecting cellulitis of the scalp with associated spondylarthropathy: case report and review. j eur acad dermatol venereol 2003, 17 (6), 689-91. 20. jacobs, f.; metzler, g.; kubiak, j.; röcken, m.; schaller, m., new approach in combined therapy of perifolliculitis capitis abscedens et suffodiens. acta derm venereol 2011, 91 (6), 726-7. 21. khaled, a.; zeglaoui, f.; zoghlami, a.; fazaa, b.; kamoun, m. r., dissecting cellulitis of the scalp: response to isotretinoin. j eur acad dermatol venereol 2007, 21 (10), 1430-1. 22. bolz, s.; jappe, u.; hartschuh, w., successful treatment of perifolliculitis capitis abscedens et suffodiens with combined isotretinoin and dapsone. j dtsch dermatol ges 2008, 6 (1), 44-7. 23. scheinfeld, n., dissecting cellulitis (perifolliculitis capitis abscedens et suffodiens): a comprehensive review focusing on new treatments and findings of the last decade with commentary comparing the therapies and causes of dissecting cellulitis to hidradenitis suppurativa. dermatol online j 2014, 20 (5), 22692. 24. marquis, k.; christensen, l. c.; rajpara, a., dissecting cellulitis of the scalp with excellent response to isotretinoin. pediatr dermatol 2017, 34 (4), e210e211. 25. navarini, a. a.; trüeb, r. m., 3 cases of dissecting cellulitis of the scalp treated with adalimumab: control of inflammation within residual structural disease. arch dermatol 2010, 146 (5), 517-20. 26. mansouri, y.; martin-clavijo, a.; newsome, p.; kaur, m. r., dissecting cellulitis of the scalp treated with tumour necrosis factor-α inhibitors: experience with two agents. br j dermatol 2016, 174 (4), 916-8. 27. wollina, u.; gemmeke, a.; koch, a., dissecting cellulitis of the scalp responding to intravenous tumor necrosis factor-alpha antagonist. j clin aesthet dermatol 2012, 5 (4), 36-9. 28. mcmullan, f. h.; zeligman, i., perifolliculitis capitis abscedens et suffodiens; its successful treatment with x-ray epilation. ama arch derm 1956, 73 (3), 256-63. 29. bellew, s. g.; nemerofsky, r.; schwartz, r. a.; granick, m. s., successful treatment of recalcitrant dissecting cellulitis of the scalp with complete scalp excision and split-thickness skin graft. dermatol surg 2003, 29 (10), 1068-70. 30. housewright, c. d.; rensvold, e.; tidwell, j.; lynch, d.; butler, d. f., excisional surgery (scalpectomy) for dissecting cellulitis of the scalp. dermatol surg 2011, 37 (8), 1189-91. skin may 2019 volume 3 issue 3 copyright 2018 the national society for cutaneous medicine 189 31. meunier, n.; zaleski, l.; bloom, d.; steger, j., treatment of dissecting cellulitis of the scalp and the use of marsupialization: a review. j dermatolog clin res: 2014; vol. 2, p 1015. 32. krasner, b. d.; hamzavi, f. h.; murakawa, g. j.; hamzavi, i. h., dissecting cellulitis treated with the long-pulsed nd:yag laser. dermatol surg 2006, 32 (8), 1039-44. 48 the newest in dermatology-acne, atopic dermatitis, actinic keratoses, psoriasis, skin cancer, and more joshua zeichner, md video length: 34:43 video description: in a cme podium lecture presented at the 2017 fall clinical dermatology conference® in las vegas, nevada, joshua zeichner, md, reviews cutting edge research presented at this year’s academic poster session, covering all aspects of dermatology. powerpoint presentation combining the 31-gene expression profile test for cutaneous melanoma with the american joint committee on cancer staging identifies the highest-risk patients with stage i-ii disease background ›cutaneous melanoma (cm) management guidelines are based on patients’ recurrence risk by stage. most newly diagnosed patients (88%) are node-negative (stage i-ii) and considered low risk. however, due to the size of the group, the majority of melanoma-associated deaths each year occur in patients diagnosed as stage i-ii.1-4 ›a subset of these patients (stage iib-iic) are currently eligible for adjuvant therapy; although, it is unclear which of these patients will benefit from and which do not need therapy.5 ›in the keynote-716 trial, patients with stage iib-iic melanoma treated with pembrolizumab saw a 9% rfs improvement, but 80% had an adverse event (16% grade 3), and 18% discontinued due to adverse events.5 ›these data emphasize the need for prognostic tools beyond current staging factors to identify patients with the highest and lowest risk of poor outcomes so that patients receive risk-aligned treatment.1-2 ›the 31-gep test has been shown in multiple prospective and independent studies to be a consistent and independent predictor of survival outcomes in large populations of patients with stage i-iii cm; clinicians use the 31-gep to guide patient management decisions.3, 610 acknowledgments & disclosures references ›bm, cnb, and ts are employees and shareholders of castle biosciences, inc. ›dh receives honoraria and is a speaker and consultant for exact sciences and castle biosciences, inc. dh receives research funding from castle biosciences, inc. ›jsb and vip have no disclosures results david hyams, md,1 jung s. byun, phd, mph,2 brian martin, phd,3 christine n. bailey, mph,3 timothy stumpf,3 valentina i. petkov, md, mph2 1desert surgical oncology, rancho mirage, ca 2surveillance research program, national cancer institute, bethesda, md, 3castle biosciences, friendswood, tx objective in collaboration with the national cancer institute’s surveillance, epidemiology, and end results (seer) program (covering 34% of the u.s. population during the study period) this study sought to: ›demonstrate the performance of the 31-gep to identify patients with high-risk tumor biology in an unselected, clinically tested cohort of patients who are node negative. ›in a large, unselected cohort of patients with stage i-ii cm, the 31-gep class 2b result identified patients with a high risk of death from melanoma who should be considered for more aggressive management. ›conversely, the high npv suggests that the 31-gep reliably identifies patients at low risk of tumor progression who could safely avoid intensive surveillance and intervention. conclusions ›seer registries linked individuals diagnosed with cm between 20132018 to data for 31-gep-tested patients (n=9,207 after exclusions). analysis focused on the subset reported as node negative (n=6,301). patient 5-year melanoma-specific survival (mss) was estimated using kaplan-meier analysis and the log-rank test. multivariable cox regression analysis was used to evaluate significant predictors of melanoma-specific death. scan or click here for more info methods 1. thomas, d. c. et al. ann surg oncol 26, 2254–2262 (2019). 2.jones, e. l. et al. jama surgery 148, 456–61 (2013). 3. greenhaw, et al. dermatol surg 44, 1494–1500 (2018). 4. o’connell, e. et al. mel research 26, 66-70 (2016). 5. luke et al. lancet, 399, 1718-1729 (2022) 6. hsueh, e. c. et al. jco precision oncology 5, 589–601 (2021). 7. vetto, j. t. et al. future oncology 15, 1207–1217 (2019). 8. podlipnik, s. et al. j eur acad dermatol venereol 33, 857–862 (2019). 9. dillon, l. d. et al. skin j cutaneous med 2, 111–121 (2018). 10. berger, a. c. et al. curr med res opin 32, 1599– 1604 (2016). figure 1. using the 31-gep in patients with a negative lymph node identifies those at highest risk of dying from their disease. table 1. multivariable analysis demonstrates independent and significant prognostic information compared to traditional staging factors melanoma-specific survival multivariable hr p-value 31-gep class 1a reference -31-gep class 1b/2a 1.56 0.232 31-gep class 2b 4.08 <0.001 age (continuous) 1.05 <0.001 ulceration (negative) reference -ulceration (present) 2.10 0.006 mitotic rate (continuous) 1.02 0.612 breslow thickness (continuous) 1.16 0.002 clinical impact ›patients with class 1a results had higher 5-year mss than those with class 1b/2a or class 2b results. ›the 31-gep had a sensitivity of 78.4% and a negative predictive value (npv) of 99.4%. ›using the 31-gep results to guide increased clinical management and surveillance for patients at high risk of melanoma-specific death may improve patient management decisions. sln neg class 1a class 1b-2b continue low intensity management consider increased intensity management, adjuvant therapy (stage iib, iic and iii) or clinical trials increased surveillance = early detection of metastasis (low tumor burden) demonstrated improved response to surgical and systemic therapy all node negative (n=6,301) class 1a class 1b/2a class 2b all 97.9% (96.7-99.2%) 95.7% (93.0-98.5%) 85.8% (80.5-91.5%) 5-year mss (95% ci) log-rank test: p<0.001 https://castlebiosciences.com/research-development/publications/ https://castlebiosciences.com/research-development/publications/ slide 1 internal use 1. bickers dr, lim hw, margolis d, et al. j am acad dermatol. 2006; 55:490-500. 2. timms rm. psychol health med. 2013; 18(3):310–320. 3. revol o, milliez n, gerard d. br j dermatol. 2015; 172(suppl 1):52–58. 4. leyden jj, sniukiene v, berk d, kaoukhov a. j drugs dermatol. 2018 mar 1;17(3):333-338 5. moore a, green lj, bruce s, et al. j drugs dermatol. 2018 sep 1;17(9):987-996. sponsored by almirall, s.a. references emmy graber,1 hilary baldwin,2 andrew f. alexis,3 james del rosso,4 richard g. fried,5 julie c. harper,6 adelaide hebert,7 leon kircik,8 evan a rieder,9 linda stein gold,10 siva narayanan,11 volker koscielny,12 ismail kasujee12 1the dermatology institute of boston and northeastern university, boston, ma; 2acne treatment and research center, brooklyn, ny; 3weill cornell medical college, new york, ny; 4jdr dermatology research/thomas dermatology, las vegas, nv; 5yardley dermatology associates, yardley, pa; 6the dermatology and skin care center of birmingham, birmingham, al; 7uthealth mcgovern medical school, houston, tx; 8icahn school of medicine, mount sinai, new york, ny; 9new york university grossman school of medicine, new york, ny; 10henry ford health system, bloomfield, mi; 11avant health llc, bethesda, md; 12almirall sa, barcelona, spain. clinician satisfaction with treatment outcomes among patients with moderate to severe non-nodular acne vulgaris (av) administered sarecycline in community practices across the u.s in proses study: analysis by concomitant medication use • acne vulgaris (av), hereinafter referred to as acne, affects up to 50 million americans and is the most common skin condition in the united states (us).1 • acne has been shown to negatively affect patient functioning, emotions, and overall qol. 2,3 • recommended treatment for moderate to severe inflammatory av are oral antibiotics. however, currently used tetracyclines like doxycycline and minocycline impose negative effects by disrupting the gastrointestinal microbiome thereby, making it challenging for patients to comply with therapy. 4 • sarecycline is a newer oral tetracycline-derived narrow spectrum antibiotic, a first line therapy treatment for moderate to severe acne patients. sarecycline is a viable option for acne patients to reduce disease burden, due to its safety profile and efficacy demonstrated in two identical phase-iii randomized, controlled trials.5 • limited data are available on clinician satisfaction with av treatment outcomes in general, and no such data is available corresponding to patients using sarecycline as monotherapy or in combination with other av treatments, in the real-world. • clinician satisfaction with sarecycline treatment outcomes (at individual patient-level) could complement clinical assessment of treatment effectiveness and could portray a full picture of value of av treatments in the real-world. background conclusions • within the study cohort administered sarecycline, a narrow-spectrum, tetracyclinederived antibiotic, for 12 weeks, for majority of patients, clinicians were very satisfied/satisfied with sarecycline treatment outcomes at week-12, and clinician satisfaction was similar among patients on sarecycline monotherapy and those on concomitant av medications. methods • a single-arm, prospective cohort study (proses) was conducted with moderate-to-severe non-nodular av patients >9 years who were prescribed sarecycline in real-world community practices in the us. • a total of 300 subjects were enrolled from 30 community practices across the u.s. • patients and clinicians completed surveys and clinical assessments at baseline and weeks 4, 8 & 12. • clinician satisfaction with sarecycline treatment outcomes was assessed at week-12, on a five-point adjectival response scale (1 (very dissatisfied)-5 (very satisfied)). • proportion of patients for whom clinicians reported very satisfied/satisfied was analyzed at week-12, as observed, for the overall study cohort, as well as stratified by the use of any concomitant av medication during the study (yes vs. no (monotherapy)). objective the objective of this analysis was to evaluate clinician satisfaction with treatment outcomes, stratified by the use or non-use of concomitant acne medications, among av patients administered sarecycline in community practices across the u.s. results table 1: patient baseline characteristics n=253 age group, % pediatric (<18 yrs) 39.92 adult (≥18 yrs) 60.08 age group, mean yrs pediatric (<18 yrs) 14.81 adult (≥18 yrs) 26.63 gender, % male 33.60 female 66.40 race,% white 66.80 other 15.81 black/african american 9.88 asian 5.93 prefer not to answer 3.16 american indian or alaskan 0.79 native hawaiian/pacific islander 0.40 ethnicity,% (hispanic, latino or of spanish origin) yes 33.99 no 66.01 baseline iga, % moderate 86.56 severe 13.44 88.98% 87.30% 11.02% 12.70% 0.00% 10.00% 20.00% 30.00% 40.00% 50.00% 60.00% 70.00% 80.00% 90.00% 100.00% sarecycline combination therapy (n=127) sarecycline monotherapy (n=126) p ro po rti on o f p at ie nt s figure 2: regardless of concomitant medication use, for majority of patients, clinicians were “very satisfied / satisfied” with sarecycline outcomes at week-12 very satisfied/satisfied other n=253 note: 0.00% of clinicians rated “very dissatisfied” with sarecycline at week-12. • a total of 253 av patients completed the study surveys at week-12 and included in the analyses. • proportion of patients with moderate/severe facial acne (per iga scores) at baseline was 100%. at week-12, patients with moderate/severe acne significantly reduced to 11.10% (p<0.0001). • for the overall cohort, for 88.14% of patients, clinicians were ‘very satisfied/satisfied’ with sarecycline treatment outcomes, at week-12 (figure 1). 0.00% 5.14% 6.72% 37.55% 50.59% 0.00% 10.00% 20.00% 30.00% 40.00% 50.00% 60.00% very dissastified dissatisfied neutral sastisfied very satisfied p ro po rti on o f p at ie nt s figure 1: for majority of patients, clinicians were “very satisfied / satisfied” with sarecycline outcomes at week-12 88.14% n=253 table 2: concomitant medication use n=253 has not used any acne medication, % 49.80 topical medication, % topical retinoids 24.51 salicylic acid 1.19 benzoyl peroxide 5.93 topical antibiotics 13.44 topical dapsone 5.14 azelaic acid 2.77 topical clascoterone 0.79 other* 17.00 oral medication^, % 4.74 *11.07% were on adapalene/benzoyl peroxide; ^4.35% were on spironolactone. venous leg ulcers (vlu), based upon revision of the starling principle in 2010 (1), are now recognized to be associated with significant dermal and deep lymphatic dysfunction in addition to chronic venous insufficiency (cvi), also known as phlebolymphedema. dermatitis is a near consistent, aggravating component of vlus and contribute to wound non-closure and early recidivism. the standard of care vlu treatment has typically focused on venous procedures/ablation in an attempt to eliminate the superficial venous hypertension component of cvi and graded compression stocking utilization with little attention to the dermatitis component (2). our wound clinic practice has begun to actively manage the dermatitis component of vlus through consistent use of 1) oral micronized purified flavanoid fraction (diosmiplex 630mg) (3,4) 2) proprietary emulsion composed of a 3:1:1 ratio of ceramide: conjugated linoleic acid: cholesterol (5,6) 3) fuzzy wale compression garment (7,8) applied under inelastic compression to achieve minimum 20-30mmhg gradient compression. synopsis results case #1 67 year old male, cvi, phlebolymphedema, complicated by work related chemical burn. non diabetic, no tobacco use. abis normal, no pad. underwent radiofrequency ablation of incompetent r gsv 2 months prior to wound clinic consult, no improvement of wound size or pain. post procedure use of standard 30-40mmhg graded static compression stocking, foam dressing to wound. multiple courses of antibiotic therapy. day 1 clinic consult photo. initiation mpff (diosmiplex 630mg), proprietary 3:1:1 ceramide dominant emulsion, fuzzy wale dermal compression under inelastic compression, hocl wound washes the synergistic, amplifying use of micronized purified flavanoid fraction, proprietary ceramide emulsion, and dermal microdeformation fuzzy wale compression under inelastic compression for the management of venous leg ulcers ■ matthew m. melin, md, facs, rpvi,faccws; jennifer reinders, wocn; angie wubben, wocn; katie cecconi, pa ■ wound healing institute, m health fairview, edina, mn objective assess use of simultaneous treatment methods for accelerated wound healing and dermatitis improvement conclusions the dermal lymphatic component of vlus and cvi remains a significantly underrecognized, underappreciated and undermanaged component of treatment, resulting in slow wound closure times and unacceptable high recidivism rates. the synergistic, amplifying, consistent application of the 4 components of oral mpff (diosmiplex 630mg), proprietary 3:1:1 ceramide dominant emulsion, fuzzy wale dermal microdeformation under inelastic compression resulted in accelerated wound closure outcomes for the 3 patient series described. the impact of oral mpff (diosmiplex 630mg) of increased lymphatic and venous tone with decreased icam and vcam, combined with direct dermal lymphatic stimulation, potentially resulting in increased lymphangion contractility, significantly reduces interstitial edema. a larger, randomized controlled clinical trial is indicated methods references 1.levick jr, michel cc. microvascular fluid exchange and the revised starling principe. cardiovascular research 2010;87:198-210.2.o’donnell tf, passman ma, et al. management of venous leg ulcers: clinical practice guidelines of the society for vascular surgery and the american venous forum. j vasc surg 2014;60:3s-59s.3.raffetto jd, eberhardt rt, dean sm, et al. pharmacologic treatment to improve venous leg ulcer healing. j vasc surg:venous and lym dis 2016;4:371-4.ulloa jh. micronized purified flavanoid fraction (mpff) for patients suffering from chronic venous disease: a review of new evidence. adv ther 2019 doi.org/10.1007/s12325-019-0884-4. p.1-6.5.choi mj, maibach hi. role of ceramides in barrier function of healthy and diseased skin. american journal of clinical dermatology 2005;6:215-223.6.sugarman jl, parish lc. efficacy of a lipid-based barrier repair formulation in moderate-to-severe pediatric atopic dermatitis. journal of drugs in dermatology 2009;8(12):1106-1111.7.ehmann s, walker kj, bailey cm, et al. experimental simulation study to assess pressure distribution of different applications applied over an innovative primary wound dressing. wounds 2020 epub august 17; 1-11. 8.wiegand c, white r. microdeformation in wound healing. wound rep reg 2013;21:793-799. a case series of three patients with cvi, phlebolymphedema, vlu and dermatitis debridement, biopsies as indicated, ankle brachial indices (abi) and venous insufficiency ultrasounds were performed patients were initiated on oral mpff (diosmiplex 630mg (vasculera)), proprietary 3:1:1 ceramide dominant emulsion (epiceram), fuzzy wale dermal microdeformation compression under inelastic compression vlu specific dressing included hocl washes and an antibacterial foam adjunctive micronutrient therapy consisting of vitamin d, c, b12 and folate are advised mthfr status is evaluate, b12 and folate are utilized if heteroor homozygous to improve endothelial functionality case #2 83 year old female, cvi, phlebolymphedema, obesity, adult onset diabetes, no pad. no h/o dvt, pe. case #3 45 year old male, obesity, aodm, prior left gsv stripping, no pad, no tobacco use. multiple episodes of cellulitis, chronic interstitial edema, lymphoedema. surgical debridement day 2 and 67 (application cadaver skin) note longitudinal dermal microdeformation from fuzzy wale day 104, closed vlu, pain markedly improved, dermatitis improved. continued daily ceramide, mpff (diosmiplex 630mg), graded compression day 1 day 67 day 104 chronic spinal stenosis, back pain, difficulty using compression stockings, chronic leg pain multiple episodes cellulitis, hospitalization for erysipelas left leg. day 1 initiated mpff (diosmiplex 630mg), proprietary 3:1:1 ceramide emulsion, fuzzy wale compression with inelastic compression (applied by husband) day 83 telehealth visit wound closed, improved dermatitis day 83 day 1 initiation mpff (diosmiplex 630mg), proprietary 3:1:1 ceramide dominant emulsion, fuzzy wale dermal compression under inelastic compression (intermittent 2 layer compression with nurse clinic changes), hocl wash. serial clinic debridement of biofilm resolution of pain day 1 day 181day 71day 49 day 1 medical writing assistance for this poster was provided by primus pharmaceuticals: m. mark melin md is a sponsored educational presenter for primus pharmaceuticals skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 185 brief article coexisting pediatric acute generalized exanthematous pustulosis and staphylococcal scalded skin syndrome cassandra beard, do, mph1, rafael mojica, bs2, sarah ferrer-bruker, do1, karthik krishnamurthy, do1 1division of dermatology, hca healthcare/mercer university school of medicine/orange park medical center program, orange park, fl 2edward via college of osteopathic medicine, spartanburg, sc acute generalized exanthematous pustulosis (agep) is a disease of acute onset, typically following drug intake. patients with agep develop an abrupt febrile eruption of pinhead-sized nonfollicular pustules on an erythematous base favoring the face or intertriginous areas. the lesions quickly spread within hours to involve the trunk and limbs.1 staphylococcal scalded skin syndrome (ssss) presents in a similar distribution with swelling and erythema with subsequent bulla formation and exfoliation.2 although rare, ssss most commonly presents in the pediatric population with an annual incidence of 7.67 per million u.s. children.3 there are far fewer reported cases of agep in the pediatric population, which is highlighted by the paucity of such incidence reports.4 we present a case of a four-yearold female whose diagnosis was complicated by overlapping features of both ssss and agep. a previously healthy four-year-old female presented to her pediatrician with a fever of 101°f/38°c, facial edema, and a shiny erythematous eruption of her face, neck, and shoulders that spread to the neck and axilla overnight. she then developed rhinorrhea and shallow perinasal erosions with yellow crusting, leading to a diagnosis of bullous impetigo. she was given topical mupirocin ointment and oral amoxicillin. the erythema continued to spread across the chest, down the back, and across the face with areas of vesiculation that ruptured, leading to crusts and scaling. she also developed radial fissuring around the mouth and eyes, clinically consistent with staphylococcal scalded skin. the following day, the exanthem evolved into a different abstract acute generalized exanthematous pustulosis is a rare drug-induced skin disorder that can present at any age. it is typically noted by swelling and erythema, with numerous facial and/or anogenital nonfollicular pustules that quickly disseminate. staphylococcal scalded skin syndrome presents with erythema and swelling that similarly favor the head and intertriginous sites with subsequent bullae formation. we present a case of a four-year-old female who presented with ssss complicated by the development of agep and discuss the course of her condition and treatment. introduction case report skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 186 figure 1. paranasal, periorbital, and frontal erosions with yellow crusting and desquamation. figure 2. popliteal advancing erythema featuring nonfollicular pustules at the edge. morphology. nonfollicular pustules developed at the advancing edge of the erythema. a wound culture of the pustules was negative for bacterial growth. a shave biopsy of the right thigh demonstrated subcorneal pustules with eosinophils, consistent with agep.5 amoxicillin was discontinued and treatment with vancomycin initiated. upon discharge two days later, the patient completed a short course of oral cephalexin and tid application of triamcinolone cream 0.1% with complete resolution of skin lesions. the subcorneal pustules are a common histological feature of both ssss and agep [6]. in our case, the presence of an inflammatory infiltrate favors agep, as ssss typically lacks inflammatory cells both in the bullae and in the underlying dermis.7 in ssss, the exfoliative toxins a and/or b released from staphylococcus aureus attack desmoglein 1, resulting in loss of adhesion of keratinocytes in the granular layer of the epidermis without apoptosis and does not elicit an inflammatory response.8,9 therefore, in ssss, early treatment with antibiotics is prudent. additional supportive care with fluid and electrolytes might result in quick recovery. patient might under short hospitalization, if intravenous antibiotics are necessary, and is advised to continue treatment for up to 15 days. in cases of agep, treatment with oral antibiotics do not provide significant improvement, and side effects from antibiotic treatment may worsen the patient’s condition.1 if the source of treatment is a cutaneous infection, topical antibiotics may be an acceptable alternative in a non-toxic discussion skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 187 pediatric patient. however, early treatment with systemic antibiotics can be lifesaving for deteriorating patients who may have disseminated staphylococcus or streptococcus infection. while agep is not associated with high rates of mortality, it is important to control in young, elderly, immunocompromised, or pregnant patients.8 alternatively, in most cases of agep, withdrawal of the offending drug and supportive care results in recovery. moist dressings and antiseptics can be considered during the pustular phase. in rare but severe cases, infliximab and etanercept have been shown to rapidly stop the pustulation and hasten recovery. in case pruritus is a prominent symptom topical steroids and other anti-pruritic creams (e.g. camphor/menthol) may be helpful. oral steroids have not been shown to shorten the overall duration of the condition or improve outcomes. if a drug reaction is suspected, patch testing can be considered.10 the presentation of ssss and agep can be differentiated clinically at their initial presentation but may appear very similar in their later stages. early on the disease process, ssss can be distinguished from agep by the presence of a scarlatiniform rash and desquamation in areas of friction e.g. the flexural folds in the absence of an iatrogenic exposure.5 although there have been rare reports of an infectious etiology in agep, most cases have been diagnosed by the onset of symptomatology within 24-48 hours following drug intake.6 the above case is interesting due to the primary diagnosis of ssss but with the complicated development of nonfollicular pustules along the advancing edge of lesional erythema following amoxicillin exposure and subsequent histological confirmation of agep. histologic features of agep include the presence of a mixed interstitial and middermal perivascular infiltrate along with necrotic keratinocytes and the absence of tortuous or dilated blood vessels, whereas the subcorneal pustules of ssss are not associated with an inflammatory infiltrate [1]. once a diagnosis of ssss or agep has been made, it is important to choose the appropriate antibiotic therapy and supportive treatment for each disease and patient population. conflict of interest disclosures: none funding: none corresponding author: cassandra beard, do, mph division of dermatology hca healthcare/mercer university school of medicine/orange park medical center program 2001 kingsley ave orange park, fl 32073 phone: 573-301-9744 email: cjbeard@atsu.edu references: 1. sidoroff a, dunant a, viboud c, halevy s, bavinck jb, et al. (2007) risk factors for acute generalized exanthematous pustulosis (agep)— results of a multinational case–control study (euroscar). br j dematol 157: 989-996. 2. napoli b, d'arpa n, d'amelio l, et al. staphylococcal scalded skin syndrome: criteria for differential diagnosis from lyell's syndrome. two cases in adult patients. ann burns fire disasters. 2006;19(4):188–191. 3. staiman, a., hsu, d. and silverberg, j. (2018), epidemiology of staphylococcal scalded skin syndrome in u.s. children. br j dermatol, 178: 704-708. 4. davidovici b, dodiuk-gad r, rozenman d. the profile of acute generalized exanthematous pustulosis in israel during the period 2002–2005. imaj 2008: 10: june: 410-412 5. henry sm, stanfield mm, dorey hf (2019) pediatric acute generalized exanthematous pustulosis involving staphylococcal scarletfever. med case rep vol. 5 no.1:88. 6. szatkowski j, schwartz ra. acute generalized exanthematous pustulosis (agep): a review and conclusion mailto:cjbeard@atsu.edu skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 188 update. journal of the american academy of dermatology. mosby inc (2015) p 843 – 848 7. de a, das s, sarda a, pal d, biswas p. acute generalised exanthematous pustulosis: an update. indian j dermatol. 2018;63(1):22–29. 8. mishra ak, yadav p, mishra a. a systemic review on staphylococcal scalded skin syndrome (ssss): a rare and critical disease of neonates. open microbiol j. 2016;10:150–159 p. 9. finlay, a. and patel, g. (2019). staphylococcal scalded skin syndrome: diagnosis and management. j clin dermatol (2003) 4: 165 10. 10. pecina jl, cappel ma. acute generalized exanthematous pustulosis. skinmed 8(4), 210– 214 p skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 556 research letters a cross-sectional study on herpes zoster diagnosis in the time of covid-19 niki nourmohammadi mph,1 katerina yale md,2 alessandro ghigi ms,3 kai zheng phd, 3 natasha a. mesinkovska md, phd2 1lake erie college of osteopathic medicine, greensburg, pa, usa 2university of california irvine school of medicine, department of dermatology, irvine, usa 3university of california irvine donald bren school of information and computer science, department of informatics, irvine, usa amidst the covid-19 pandemic, several published reports note concomitant cases of herpes zoster (hz) infections in covid-19 positive patients, suggesting a potential coexistence of the two viruses, or an increased incidence of hz in this population (1-4). in order to investigate the credibility of this association and determine whether the covid-19 pandemic has truly affected the overall incidence of hz, we analyzed the university of california covid research data set (uc cords). this centralized, de-identified database provides access to health records for patients with covid-19 pcr testing across abstract background: the covid-19 pandemic has presented various cutaneous manifestations in covid19 positive patients, including rising cases of herpes zoster (hz). objective: our investigation sought to assess the proposed association between a positive covid19 test result and herpes zoster, and determine whether the covid-19 pandemic has affected the overall incidence of hz. methods: in this large crosssectional study, patients were collected from university of california covid research data set (uc cords), a centralized, rapidly accumulating de-identified database and were then divided into those diagnosed with hz before covid test and those with hz diagnosis after covid testing. the total number of hz cases to the total number of medical visits during the same six-month time frame (march to august) in 2019 and 2020 were also collected to assess if covid-19 impacted the hz incidence. results: a total of 608 patients were diagnosed with hz from march 1 to august 31, 2020; of which, 2.1% (n=13) tested positive and 97.9% (n=595) tested negative for covid-19. from march to august 2019 there were 4,349 reported hz cases, and in comparison, there were 3,551 reported cases of hz in 2020, a significant decrease (χ2 =90.6454, p<.00001). conclusion: there was no evidence to substantiate an association between hz and covid-19. the overall decrease in hz incidence may be due to patients less likely to seek medical care. introduction skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 557 five uc medical institutions: davis, irvine, los angeles, san diego and san francisco (5). from march 1 to august 31, 2020, it contains patient demographics, medical history, medical visit type (including inpatient, outpatient, and telehealth), and covid-19 status on 226,093 patients. patients collected from the uc cords were divided into two subgroups, those with a diagnosis code for hz before covid test and those with hz after covid testing within two months, prior or subsequent, of each other, to assess whether one infection may indicate the development of the other. to analyze whether there was an increase in the hz condition rate during the pandemic, we compared the total number of hz cases to the total number of medical visits during the same six-month time frame (march to august) in 2019 and 2020 using the general de-identified uc health data warehouse (uchdw). statistical analysis was completed using chisquared tests to determine a significant relationship between those with or without hz and covid-19 infections. to analyze whether there was an increase in the hz condition rate during the pandemic, we compared the total number of hz cases to the total number of medical visits during the same six-month time frame (march to august) in 2019 and 2020 using the general de-identified uc health data warehouse (uchdw). statistical analysis was completed using chisquared tests to determine a significant relationship between those with or without hz and covid-19 infections. a total of 608 patients were diagnosed with hz from march 1 to august 31, 2020; of which, 2.1% (n=13) tested positive and 97.9% (n=595) tested negative for covid19 (table 1). when compared to the overall covid-19 positive test rate of 3.9% in the uc cords, the incidence of covid-19 was lower in patients with hz (χ2 = 4.9331, p=.0264). among patients with an hz diagnosis prior to covid-19 testing, only one patient (0.3%) developed hz within two months prior to covid-19 diagnosis. comparatively, among patients with a hz diagnosis within two months subsequent to covid-19 testing, only three patients (1.0%) tested positive; one of which was diagnosed with hz on the same day as covid-19. table 1. patients with herpes zoster diagnosis who underwent covid testing (uc cords) in march to august 2020 condition (age range, avg age) total, n covid-19 (+), n (%) covid-19 (-), n hz diagnosis from march 1 to august 31, 2020 (8-89, 59y) 608 13 (2.1%) 595 male 248 2 (0.8%) 246 female 360 11 (3.1%) 349 hz diagnosis within 2 months prior to covid19 test (11-89, 60y) 340 1 (0.3%) 339 male 138 0 (0%) 138 female 202 1 (0.5%) 201 hz diagnosis within 2 months after covid-19 test (11-89, 58y) 297 3 (1.0%) 294 male 130 1 (0.8%) 129 female 167 2 (1.2%) 165 within the uchdw, from march to august 2019 there were 4,349 reported hz cases (n=1,697,851), and in comparison, there were 3,551 reported cases of hz in 2020 (n=1,718,275) (table 2). these results methods results skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 558 demonstrate an hz condition rate of 0.0026 in 2019 and 0.0021 in 2020 (χ2 =90.6454, p<.00001), indicating a significant decrease. table 2. cases of herpes zoster recorded during covid-19 pandemic march-august 2019 vs. 2020 (de-identified uchdw) time period (avg age) herpes zoster cases, n condition rate marchaugust 2019 (61y) 4349 0.0026 marchaugust 2020 (60y) 3551 0.0021 in this study we did not find evidence to substantiate an association between hz diagnosis and covid-19. additionally, the data suggests that, during the covid-19 pandemic, there has been no increase in medical visits for hz in the uc medical system, both in person and by telehealth. limitations include use of tertiary center data, lack of clinical details, such as hz location or disease treatment, due to deidentified data, rapidly changing testing criteria and availability, and inability for longitudinal follow-up. we recognize the overall number of hz cases may be lower due to less patients seeking medical care due to the pandemic, leading to an apparent negative correlation between hz and covid-19. future studies with larger databases may help better assess the details of this relationship. in this limited dataset, there was no evidence to substantiate an association between hz and covid-19 infection, nor was there an increase in the number of cases of hz during the time of the covid19 pandemic. conflict of interest disclosures: the project described was supported by the national center for research resources and the national center for advancing translational sciences, national institutes of health, through grant ul1 tr001414. the content is solely the responsibility of the authors and does not necessarily represent the official views of the nih. funding: none corresponding author: niki nourmohammadi mph lake erie college of osteopathic medicine at seton hill 20 seton hill dr. greensburg, pa 15601 phone: 949 903-3584 email: nnourmoham98861@med.lecom.edu references: 1. tartari f, spadotto a, zengarini c, et al. herpes zoster in covid-19-positive patients. int j dermatol. 2020;59(8):1028-1029. doi:10.1111/ijd.15001 2. shors ar. herpes zoster and severe acute herpetic neuralgia as a complication of covid-19 infection. jaad case rep. 2020;6(7):656-657. doi:10.1016/j.jdcr.2020.05.012 3. ertugrul g, aktas h. herpes zoster cases increased during covid-19 outbreak. is it possible a relation? [published online ahead of print, 2020 jul 7]. j dermatolog treat. 2020;1. doi:10.1080/09546634.2020.1789040 4. de freitas ferreira aca, romão tt, silva macedo y, pupe c, nascimento oj. covid-19 and herpes zoster co-infection presenting with trigeminal neuropathy [published online ahead of print, 2020 may 24]. eur j neurol. 2020;10.1111/ene.14361. doi:10.1111/ene.14361 5. university of california. 2020. university of california health creates centralized data set to accelerate covid-19 research. [online] available at: <https://www.universityofcalifornia.edu/pressroom/university-california-health-createscentralized-data-set-accelerate-covid-19research> [accessed 12 august 2020] discussion conclusion skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 152 brief article an uncommon location for granular cell tumor in a 10-year-old caucasian female joanna trigg, do1, stefanie cubelli, do, mbs1, graham h. litchman, do, ms1, jason a. cohen, md2, suzanne sirota rozenberg, do, faocd, faad1 1department of dermatology, st. john’s episcopal hospital, far rockaway, ny 2dermpath diagnostics, white plains, ny granular cell tumor is a term used to describe a group of soft tissue neoplasms with cells that are made of granular cytoplasm from the accumulation of lysosomal granules.1 granular cell tumors are rare tumors that mostly occur in adults between 30 and 60 years old, with a 1:3 male-to-female ratio, and most often in individuals of african descent.1,4 most cases present as a poorly defined solitary tumor and a large majority are typically found in the head and neck regions, with 30% located on the tongue because they develop from the gastrointestinal mucosa.3,5 there have been 5,039 reported granular cell tumors, of which only 128 are pediatric cases. given the rarity of these tumors, especially in the pediatric population, clinical diagnosis is difficult and histopathologic analysis is often necessary. here we report a case of a granular cell tumor in a 10-yearold caucasian female. a 10 year old caucasian girl without prior medical conditions presented with a solitary bump on the left upper extremity present for an unknown amount of years. they denied pain, discharge from the area, or changes in growth of the lesion over time. the patient denied fever or chills. on physical exam, the left ventral extremity had a slightly pink/flesh-colored, indurated, round nodule. there was no opening to the surface of the skin (figure 1). a 2mm punch biopsy revealed a proliferation of cells with oval and round nuclei and abundant cytoplasm filled with granules (figure 2) arranged in nested aggregations throughout the dermis, without mitotic figures or atypia noted (figures 3) consistent with granular cell tumor. based on the pathology reading and the fact that it was a small, solitary lesion, the tumor was very likely benign. however, given abstract granular cell tumors are uncommon soft-tissue neoplasms of confirmed neural origin and are typically found in females of african descent between 30 and 60 years old.1-3 most cases are found in the head and neck region, specifically the tongue, although there have been reports of other anatomic variants in patients outside of the typical epidemiology. we report a case of a granular cell tumor in a 10-yearold caucasian female located on the left ventral upper arm with a biopsy confirming the histopathological diagnosis. introduction case presentation skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 153 extension into the peripheral margin and that some cells were found around peripheral nerves, the patient ideally would have had a wide excision of the lesion to minimize the chance of recurrence. unfortunately, she was lost to follow up. figure 1. granular cell tumor on proximal left arm of the patient. most granular cell tumors present as asymptomatic, skin-colored to brown/red, firm dermal or subcutaneous nodules.1,8 they typically range in size from 0.5-3.0cm. at times, the surface might be ulcerated or verrucous.8 some lesions might also elicit pain or pruritus. they are usually slow growing benign tumors found in the oral cavity in females ages 30-50 years old of african descent. this demographic differed from that in our case of a 10-year-old caucasian female. there are three variants of granular cell tumors. the first normal variant described above, which positively expresses the s100 protein. 8, 11 the second is a non-neural granular cell tumor which has similar features to the normal variant, but is s100 negative. the third is a congenital granular lesion that is typically located in the gingiva of newborns, and is also s100 negative. histologically, the dermis shows a nodule made of polygonal, pale-staining cells with abundant lysosomal granules which give it the name “granular cell tumor”. one to three percent of cases are found to be malignant and are more likely to occur when the original tumor is found in viscera or deep soft tissue.4 figure 2. granular cell tumor with cells that have abundant cytoplasm filled with granules and nuclei that are oval and round. no mitotic figures or atypia noted.7 (h&e, 20x) figure 3. cells arranged in nested aggregations throughout the dermis.7 (h&e, 200x) discussion skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 154 these malignant tumors also have a risk of metastasizing to regional lymph nodes, and, in even rarer cases, to the lungs or bone.9 benign characteristics of granular cell tumors include: (1) origination within the skin; (2) less than 3 cm diameter; and (3) no new growth in long-standing lesions.10 there have been attempts to develop histopathologic criteria to identify malignant tumors. kim and lee report that malignancy criteria include necrosis, spindling, vesicular nuclei with large nucleoli, increased mitotic activity (more than 2 mitoses per 10 high power fields at 200 magnification), high nuclear to cytoplasmic ratio, and pleomorphism.10 if 3 or more of these criteria are present, the tumor can be termed malignant.6, 10 if one or two criteria are found, then the tumor may be considered atypical.6 if only one criterion is met, the tumor is classified as benign. in this case, our patient had both clinical and histopathologic characteristics of a benign granular cell tumor. clinical differential diagnosis includes dermatofibroma, regressing verruca, adnexal neoplasms, basal cell carcinomas, leiomyomas, and leiomyosarcomas and even squamous cell carcinoma if the tumor is located near an epithelial surface and demonstrates pseudoepitheliomatous hyperplasia.5,9, 10 because a granular cell tumor is uncommon and has no specific clinical features, diagnosis can be clinically challenging. treatment of granular cell tumors is with complete excision. there is a higher local recurrence rate if the tumor is not excised with clear margins, likely due to plexiform or perineurial growth patterns.1 kim and lee report that tumors on extremities could infiltrate deeper than clinically expected, and a wider, deeper margin should be considered.10 depending on location, further surgical management may be appropriate. granular cell tumors are rare soft tissue neoplasms. they are most likely found in the head and neck region of females between 30 and 60 years old. however, tumors have been reported in unusual populations, specifically, in pediatric patients. therefore, granular cell tumors should be considered in the differential diagnosis of a solitary lesion on the extremity of a pediatric patient. conflict of interest disclosures: none funding: none corresponding author: steganie cubelli do, mbs 9 drake court, boonton, nj 07005 phone: 201-213-1503 email: cubelli90@gmail.com references: 1. argenyi zb. neural and neuroendocrine neoplasms (other than neurofibromatosis). in: dermatology. vol 115. philadelphia, pa: elsevier; 2016:2050-2067. 2. daulatabad d, grover c, tanveer n, bansal d. granular cell tumor in a child: an uncommon cutaneous presentation. indian dermatology online j . 2016;7(5):390-392. 3. yasak t, ozkaya o, ayberk a, kayadibi t, erzurumluoglu n. report of two cases of granular cell tumor, a rare tumor in children. j pediatr surg case rep. 2016;14:1-3. 4. patterson jw. neural and neuroendocrine tumors. in: weedon's skin pathology. vol 37. 4th ed. philadelphia, pa: elsevier; 2016:1041-1067. 5. goldblum jr. soft tissues. in: rosai and ackerman's surgical pathology. vol 41. 11th ed. philadelphia, pa: elsevier; 2018:1810-1914. 6. fanburg-smith jc, meis-kindblom jm, fante r, kindblom l-g. malignant granular cell tumor of soft tissue: diagnostic criteria and clinicopathologic correlation. the am j surg pathol. 1998;22(7):779794. 7. cohen, j. figures 2,3. dermpath diagnostics. port chester, ny. 2018 8. james w, berger t, elston d. dermal and subcutaneous tumors. in: andrews' diseases of the conclusion skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 155 skin . vol 28. 12th ed. philadelphia, pa: elsevier; 2016:579-624. 9. gunduz o, erkin g, bilezikci b, adanali g. slowly growing nodule on the trunk: cutaneous granular cell tumor. dermatopathology. 2016;3:23-27. 10. kim hj, lee m-g. granular cell tumors on unusual anatomic locations. yonsel medical journal. 2015;56(6):1731-1734. doi:http://dx.doi.org/10.3349/ymj.2015.56.6.1731 11. goldblum j, folpe a, weiss s. benign tumors of peripheral nerves . in: enzinger and weiss's soft tissue tumors. 6th ed. philadelphia , pa: elsevier; 2014:784-854. skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 189 compelling comment a commentary on colorism and skin bleaching in asian and asian american patients kezia i. surjanto bs1, michael b. phan bs2, laura williams md1 1tulane university school of medicine, new orleans la 2university of texas medical branch, school of medicine, galveston tx the light-skinned asian beauty standard that is prevalent today may have roots in colorism that extend far back into asian history. colorism is a bias according to a skin color hierarchy within ethnoracial groups that leads to systematic discrimination against individuals with darker skin tones.1,2 in japan, light skin reflected nobility based on the implication that fair-skinned individuals were exempt from outdoor labor.1,2 in india, possessing darker skin implied that one was of a lower caste.2 similar colorism trends were also present in china, pakistan, vietnam, korea, the philippines, cambodia, thailand, and indonesia, ultimately associating fair skin with improved social privilege and beauty.1, 2 these biases impact individuals whose skin tone does not conform to the culturally rooted standard that is perpetuated throughout generations. the discrimination seeps into their education and employment, rendering them vulnerable to skin tone specific microaggressions and potential internalized feelings of inferiority compared to their fairskinned counterparts.2 as a result, asians and asian americans use skin bleaching products, despite their ingredients’ adverse effects which include, but are not limited to: exogenous ochronosis (hydroquinone), membranous nephropathy (mercury), and superficial mycoses (steroids).1,3 with this in mind, one can understand that the practice of skin bleaching is not only an attempt to attain beauty, but also a means to evade skin tone specific discrimination.2 it is crucial for dermatologists— especially those serving a diverse patient demographic— to be aware of the origins of skin bleaching and approach patients suspected of this practice from a culturally sensitive perspective. dermatologists have the opportunity for educating patients while remaining open to their needs, especially if they suffer from pigmentary disorders and are pursuing lightening outside of a purely cosmetic reason. this approach may produce better health outcomes in these patients and improve physician-patient relationships. conflict of interest disclosures: none funding: none corresponding author: kezia surjanto 1430 tulane ave new orleans, la 70112 phone: 949-637-8614 email: ksurjanto@tulane.edu references: 1. gupta ma, gupta ak. the color of skin: psychiatric ramifications. clin dermatol. 2019;37(5):437-446. 2. bettache k. a call to action: the need for a cultural psychological approach to discrimination on the basis of skin color in asia. perspect psychol sci. 2020;15(4):1131-1139. 3. mahé a. the practice of skin-bleaching for a cosmetic purpose in immigrant communities. j travel med. 2014;21(4):282-287. mailto:ksurjanto@tulane.edu skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 109 short communications a female with thick intertriginous vegetative plaques brandon t. beal, md1; hannah cundall bs2; anthony p. fernandez, md, phd3 1department of dermatology, cleveland clinic, cleveland, oh 2school of medicine, case western reserve university, cleveland, oh 3department of dermatology, cleveland clinic, cleveland, oh a woman in her 80’s presented with exudative, malodorous, and vegetative plaques in the bilateral axillary vault, groin, and right inframammary fold for 18 months (figure 1). her past medical history was significant for a remote history of breast cancer treated with unilateral left mastectomy without recurrence. she denied history of inflammatory bowel disease (ibd) and gastrointestinal symptoms. oral and ocular examinations were unremarkable. work-up was notable for a peripheral eosinophilia (24.1%). indirect immunofluorescence (if) for igg and igg4 antibodies and enzymelinked immunosorbent assay (elisa) for desmoglein (dsg) 1 and 3 antibodies were negative. a 4-mm punch biopsy was obtained (figure 2). direct immunofluorescence (dif) to evaluate for pemphigus vegetans revealed weak granular deposition of complement c3 at the basement membrane zone. pyodermatitis vegetans (pdv) is a rare cutaneous inflammatory disease characterized by thick intertriginous vegetative plaques and peripheral eosinophilia (1). pyostomatitis vegetans is characterized by pustular and vegetative plaques of the oral mucosa, and is considered to be the oral equivalent of pdv. pyodematitis-pyostomatitis vegatans is often associated with ibd, in particular ulcerative colitis (2,3). pdv can be difficult to distinguish from pemphigus vegetans, a rare autoimmune bullous disease, since the two disorders share many clinical and histologic features. figure 1: plaques present in the inframammary fold. case report discussion skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 110 figure 2: lesional hematoxylin-eosin staining demonstrated mild spongiosis with abundant eosinophils, prominent epidermal acanthosis, intraepidermal microabscesses with eosinophils, and a dense perivascular and interstitial inflammatory infiltrates with eosinophils and neutrophils. common histologic findings in pdv include intraepidermal eosinophilic microabscesses, eosinophilic and neutrophilic infiltrates, and acanthosis (1,4). unlike pdv, pemphigus vegetans is not associated with ibd (5). dif and if are crucial to distinguish between these disorders (4). pemphigus vegetans dif demonstrates igg and c3 epidermal deposits and if or elisa reveals igg antibodies against dsg 3 (4). in summary, we present a case of pdv without mucosal involvement and not associated with ibd. this case highlights a rare disease entity whose clinical and histologic features are important for dermatologists and dermatopathologists to be knowledgeable about. conflict of interest disclosures: none. funding: none. corresponding author: brandon t. beal, md department of dermatology, cleveland clinic cleveland, oh bealb@ccf.org references: 1. matias f, rosa d, carvalho m, castanon mc. pyodermatitis-pyostomatitis vegetans: case report and review of medical literature. an bras dermatol 2011; 86 (4 suppl): s137-40. 2. clark l, tolkachjov s, bridges a, camilleri m. pyostomatitis vegetans (psv)pyodermatitis vegetans (pdv): a clinicopathologic study of 7 cases at a tertiary referral center. jaad 2016; 75: 578-584. 3. dodd em, howard jr, dulaney ed, rosenthal si, wanna mr, farah rs. pyodermatitis-pyostomatitis vegetans associated with asymptomatic inflammatory bowel disease. international journal of dermatology 2017. 4. nico m, hussein t, aoki v, lourenco s. pyostomatitis vegetans and its relation to inflammatory bowel disease, pyoderma gangrenosium, pyodermatitis vegetans, and pemphigus. journal of oral pathology & medicine 2012; 584-588. 5. nigen s, poulin y, rochette l, lévesque mh, gagné e. pyodermatitis-pyostomatitis vegetans: two cases and a review of the literature. j cutan med surg. 2003; 7: 250-5. https://www.ncbi.nlm.nih.gov/pubmed/?term=dodd%20em%5bauthor%5d&cauthor=true&cauthor_uid=28474357 https://www.ncbi.nlm.nih.gov/pubmed/?term=howard%20jr%5bauthor%5d&cauthor=true&cauthor_uid=28474357 https://www.ncbi.nlm.nih.gov/pubmed/?term=dulaney%20ed%5bauthor%5d&cauthor=true&cauthor_uid=28474357 https://www.ncbi.nlm.nih.gov/pubmed/?term=dulaney%20ed%5bauthor%5d&cauthor=true&cauthor_uid=28474357 https://www.ncbi.nlm.nih.gov/pubmed/?term=rosenthal%20si%5bauthor%5d&cauthor=true&cauthor_uid=28474357 https://www.ncbi.nlm.nih.gov/pubmed/?term=wanna%20mr%5bauthor%5d&cauthor=true&cauthor_uid=28474357 https://www.ncbi.nlm.nih.gov/pubmed/?term=farah%20rs%5bauthor%5d&cauthor=true&cauthor_uid=28474357 poster presented at the winter clinical dermatology conference, january 12–17, 2018, lahaina, hi, usa introduction • the optima (efficacy of optimized retreatment and step-up therapy with omalizumab in patients with chronic idiopathic/ spontaneous urticaria [ciu/csu]; nct02161562) study was designed to address some of the key gaps in the knowledge of optimal ciu/csu treatment with omalizumab • owing to the intermittent nature of ciu/csu, physicians may want to consider stopping omalizumab treatment in patients who are symptom free for a period of time • symptoms may re-emerge after a period of treatment withdrawal; the primary objective of the study was therefore to determine the efficacy and safety of retreatment in patients who respond to an initial course of omalizumab omalizumab retreatment of patients with chronic idiopathic urticaria/spontaneous urticaria (ciu/csu) following return of symptoms: primary results of the optima study gordon sussman,1 jacques hébert,2 wayne gulliver,3 charles lynde,4 william h. yang,5 olivier chambenoit,6 antonio vieira,7 frederica detakacsy,7 lenka rihakova7 1department of medicine, university of toronto, toronto, on, canada; 2department of medicine, centre hospitalier de l’université laval, québec, qc, canada; 3faculty of medicine, memorial university of newfoundland, st. john’s, nl, canada; 4lynde institute for dermatology, markham, on, canada; 5ottawa allergy research corporation, university of ottawa medical school, on, canada; 6novartis pharmaceuticals corporation, east hanover, nj, usa; 7novartis pharmaceuticals canada inc., dorval, qc, canada references 1. clinicaltrials.gov – nct02161562. 2. sussman g, et al. design and rationale of the optima study: retreatment or step-up therapy with omalizumab in patients with chronic idiopathic/ spontaneous urticaria (ciu/csu). wcdc 2018. poster. acknowledgments the complete optima study team comprised: 35 active sites in the following countries: argentina, brazil, canada, chile, dominican republic, guatemala, mexico, and panama; syreon clinical research for project management, data management, and medical writing; and novartis pharmaceuticals canada and novartis in participating countries. all authors participated in the development of the poster and approved the final poster for presentation. editorial assistance in the development of this poster was provided by jessica donaldson-jones of fishawack communications ltd, abingdon, uk. this poster was previously presented at the european academy of allergy and clinical immunology congress, june 17–21, 2017, helsinki, finland, and at the fall clinical dermatology conference, october 12–15, 2017, las vegas, nv, usa. funding this study was funded by novartis pharmaceuticals canada inc. disclosures authors declare the following, real or perceived conflicts of interest: gs, jh, wg, cl, and why received honoraria as investigators and consultants. gs received honoraria as speaker of this corresponding study. oc, av, fdt, and lr are employees of novartis pharmaceuticals. contact information lenka rihakova – lenka.rihakova@novartis.com antonio vieira – antonio.vieira@novartis.com novartis pharmaceuticals canada: +1(514) 631 6775 • if patients relapsed (uas7 ≥16) upon withdrawal, they were retreated with their starting dose for 12 weeks inclusion criteria • men or women at least 18 years of age • diagnosis of ciu/csu and the presence of symptoms for ≥6 months prior to the screening visit • patients must have been on an approved dose of nonsedating h1-antihistamine for ciu/csu, and no other concomitant ciu/ csu treatment, for at least the 7 consecutive days immediately prior to the randomization visit and must have documented current use on the day of the randomization visit • uas7 ≥16 (scale 0−42) and itch component of uas7 ≥8 (scale 0−21) during 7 days prior to randomization exclusion criteria • patients with a clearly defined underlying etiology for chronic urticaria other than ciu/csu • patients with urticarial vasculitis, urticaria pigmentosa, erythema multiforme, mastocytosis, hereditary or acquired angioedema, lymphoma or leukemia, active atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus, or other skin disease associated with itch that could interfere with study outcomes conclusions • after being well controlled (uas7 ≤6), upon withdrawal 44.4% of patients on omalizumab 150 mg and 50.0% of patients on omalizumab 300 mg relapsed (uas7 ≥16) • the overall time to relapse for both dosages was 4.7 weeks • retreatment with both dosages is effective. overall, 87.8% of patients regained symptom control upon retreatment, after initially being well controlled and subsequent relapse table 1. demographics and baseline characteristics characteristic omalizumab 150 mg (n=178) omalizumab 300 mg (n=136) overall (n=314) age, mean (range), years 46.7 (18–79) 45.8 (20–78) 46.3 (18–79) gender, % male female 27.0 73.0 27.2 72.8 27.1 72.9 race, % white asian black am. indian/alaska native other 76.4 8.4 5.6 1.1 8.4 83.1 7.4 4.4 2.2 2.9 79.3 8.0 5.1 1.6 6.1 time to ciu/csu symptoms, n (%) ≤1 year >1–≤2 years >2–10 years >10 years 28 (15.7) 25 (14.0) 84 (47.2) 41 (23.0) 22 (16.2) 25 (18.4) 54 (39.7) 35 (25.7) 50 (15.9) 50 (15.9) 138 (43.9) 76 (24.2) baseline uas7, mean (range) 29.7 (16.0–42.0) 30.0 (16.0–42.0) 29.8 (16.0–42.0) # prior medications used for ciu/csu, mean (range) 1.8 (0.0–12.0) 2.1 (0.0–8.0) 1.9 (0.0–12.0) ciu/csu, chronic idiopathic/spontaneous urticaria; uas7, weekly urticaria activity score. discontinued 10 patients (5.6%) not controlled – step-up 141 patients (79.2%) discontinued 5 patients (3.7%) well controlled 88 patients (64.7%) relapsers 44 patients (50.0%) nonrelapsers 44 patients (50.0%) nonrelapsers 15 patients (55.6%) well controlled 27 patients (15.2%) relapsers 12 patients (44.4%) extended treatment 43 patients (31.6%) omalizumab 300 mg 136 patients omalizumab 150 mg 178 patients 314 randomized patients figure 3. disposition after withdrawal period – patients to receive retreatment 314 randomized patients omalizumab 150 mg, 178 patients omalizumab 300 mg, 136 patients figure 2. patient randomization ratio table 2. mean time to relapse omalizumab 150 mg omalizumab 300 mg overall 4.8 weeks 4.7 weeks 4.7 weeks 40 35 30 25 20 m e a n ( 9 5 % c i) u a s 7 15 10 5 0 day 0 month 1 month 2 month 3 1st dosing period month 4 month 5 month 6 month 7 month 8 month 9 month 10 month 11 omalizumab 150 mg (n=12) 29.8 1.3 3.8 29.4 omalizumab 300 mg (n=37a) 30.1 1.2 28.3 2.3 withdrawal period 2nd dosing period figure 4. mean uas7 of retreated patients throughout the study a7 out of 44 patients on omalizumab 300 mg did not complete the 2nd dosing period or did not submit the participant diary as per protocol. ci, confidence interval; uas7, weekly urticaria activity score. p a ti e n ts ( % ) omalizumab 150 mg (n=12) omalizumab 300 mg (n=37a) 83.3% 89.2% 87.8% overall (n=49) 100 75 50 25 0 figure 5. proportion of patients regaining symptom control upon retreatment a7 out of 44 patients on omalizumab 300 mg did not complete the 2nd dosing period or did not submit the participant diary as per protocol. error bars represent 95% confidence intervals. objectives • four objectives were to be answered in optima: − if a patient is well controlled and therefore treatment is stopped, will the patient relapse? how long will it take to relapse? − if treatment is restarted, will the patient respond to retreatment? − if the patient does not respond to omalizumab 150 mg, will step-up therapy help? − if the patient does not respond to omalizumab 300 mg, will treatment extension help? • this poster will cover the first two questions methods study design • optima is a phase 3b, international, multicenter, randomized, open-label, noncomparator study.1 for details about the study design, please see the companion poster being presented at this congress (sussman, et al. wcdc 2018)1,2 • patients with ciu/csu who were symptomatic despite h1-antagonists were randomized 4:3 to omalizumab 150 mg or 300 mg for 24 weeks (1st dosing period) • based on weekly urticaria activity score (uas7), patients entered one of the following phases: treatment withdrawal (if uas7 ≤6), step-up to 300 mg (if 150 mg initially and uas7 >6 at weeks ≥8 to 24), or continued treatment for 12 more weeks (if 300 mg initially and uas7 >6 at week 24) • patients with a history of malignancy of any organ system • patients should stay on same approved dose of nonsedating h1-antihistamine during all trial duration. no rescue medication is allowed results baseline characteristics uas7 >6 omalizumab 150 mg screen & washout g ro u p a g ro u p b uas7 ≤6 uas7 <16 omalizumab 300 mg r a n d o m iz a ti o n 4 :3 −5 to −1week 0 4 8 12 16 2420 0 4 8 12 0 4 uas7 ≤6 uas7 <16 omalizumab 300 mg omalizumab 300 mg uas7 >6 screen 1st dosing study treatment withdrawal 2nd dosing follow-up 0 4 8 omalizumab 300 mg stop therapy uas7 ≥16 stop therapy uas7 ≥16 follow-up omalizumab 150 mg figure 1. study design for retreated patients uas7, weekly urticaria activity score. scan this qr code visit the web at: http://novartis.medicalcongressposters.com/default.aspx?doc=e4212 mobile friendly e-prints 3 ways to instantly download an electronic copy of this poster to your mobile device or e-mail a copy to your computer or tablet text message (sms) text: qe4212 to: 8nova (86682) us only +18324604729 north, central and south americas; caribbean; china +447860024038 uk, europe & russia +46737494608 sweden, europe standard data or message rates may apply. skin january 2019 volume 3 issue 1 copyright 2018 the national society for cutaneous medicine 49 compelling comments fast absorbing cat-gut sutures jake a gibbons, bs1, tyler marions, bs, mba1 1university of texas medical branch school of medicine, galveston, tx before becoming mainly synthetic in the 20th century, sutures consisted primarily of natural materials.1 catgut, an absorbable suture, is of historical interest as its use dates back to 175 a.d.2 despite the name, catgut has no relation to the common household pet. the word is likely derived from “kitgut,” a word for a fiddle with strings constructed from sheep intestine. the catgut suture was, in fact, made from the small intestine submucosa of sheep and the small intestine serosa of cattle.2 catgut is absorbed rapidly compared to other absorbable sutures. catgut elicits an inflammatory response from the host, leading to the breakdown and absorption of the suture. this process results in catgut retaining little tensile strength after two weeks.2 professor joseph lister was one of the first individuals to study the absorbability of catgut. he experimented by tying catgut around the carotid artery of a calf. after the calf was killed thirty days later, lister reexamined the knot and found that the suture was no longer present and had been replaced with living tissue. lister applied his own antiseptic techniques during his experimentation with the suture, as he understood the risk of infection when exposing patients to raw intestine.3 further advancements in the development of absorbable sutures were made, leading to the development of sutures such as polyglycan 910 and polyglycolic acid. these sutures provide additional tensile strength and knot security, while eliciting less tissue inflammation.1 though absorbable gut sutures are not used superficially for skin closure, they are used by dermatologists in sewing split thickness skin grafts in sensitive areas of the face and in the mouth to promote rapid healing and obviate the need for suture removal. historically, the use catgut for generations was an imperative stepping stone for the development of fast absorbing sutures still used today. conflict of interest disclosures: none. funding: none. corresponding author: jake gibbons, bs the university of texas medical branch galveston, tx jagibbon@utmb.edu references: 1. swanson na, tromovitch ta. suture materials, 1980s: properties, uses, and abuses. international journal of dermatology. 1982;21(7):373-378. doi:10.1111/j.13654362.1982.tb03154.x. mailto:jagibbon@utmb.edu skin january 2019 volume 3 issue 1 copyright 2018 the national society for cutaneous medicine 50 2. roenigk rk, roenigk hh. roenigk & roenigks dermatologic surgery: principles and practice. new york: m. dekker; 1996. 3. holder ej. the story of catgut. postgraduate medical journal. 1949;25:427-433. skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 332 brief articles resolution of post-surgical hypergranulation tissue with topical aluminum chloride giselle prado mda, anna nichols md, phdb, martin zaiac mdc anational society for cutaneous medicine, new york, ny bdepartment of dermatology & cutaneous surgery, university of miami miller school of medicine, miami, fl cgreater miami skin and laser center, miami beach, fl hypergranulation, also commonly referred to as overgranulation or proud flesh, is the extension of granulation tissue beyond the amount required to close a tissue defect.1 this is an infrequent, albeit not entirely rare, occurrence in wound healing. hypergranulation tissue presents as a moist, vascular, red tissue with a granular surface that extends above the level of the surrounding skin. newly formed epithelial tissue at the edges of the granulation tissue may be seen proliferating towards the center. histologically, this tissue is comprised of a dense network of capillaries, many fibroblasts and macrophages, and newly created collagen fibers.1 there are three phases in wound healing: inflammation, proliferation, and maturation. hypergranulation can occur during the proliferative phase of wound healing. normally, granulation tissue fills in wounds by growing from the base of the wound until becoming level with the surface of the skin.1 in hypergranulation, the granulation tissue continues to proliferate beyond the height of the wound surface. this impairs reepithelialization from the wound edge because the epithelial cells must now migrate vertically to achieve closure. many treatment options for hypergranulation have been reported in the literature including: silver nitrate, both topical and intralesional corticosteroids, laser ablation, hydrocolloid dressings, trichloroacetic acid, polyurethane abstract hypergranulation is the extension of granulation tissue beyond the required amount to close a tissue defect. we report our experience using aluminum chloride to treat a series of two patients with hypergranulation tissue. both patients had lengthy treatment courses after mohs surgery with growth of hypergranulation tissue that resolved once aluminum chloride was placed on the wound. aluminum chloride is a useful hemostatic agent frequently employed in dermatology. it is a readily available and low-cost option for management of hypergranulation after dermatologic procedures. chronic wounds are a common treatment challenge for clinicians. due to its affordability and availability, clinicians may consider topical aluminum chloride when managing post-surgical hypergranulation tissue. introduction skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 333 foam, surgical excision, both sugar and salt application, and enzymes such as papain. traditionally, chemical cautery with silver nitrate has been used as the last resort treatment option after milder methods have failed. the use of aluminum chloride to treat hypergranulation tissue has not been explored extensively in the literature. at the present time, no cases describing the management and long-term clinical outcomes of the use of aluminum chloride to treat hypergranulation could be found. we report our experience using aluminum chloride to treat a series of two patients with hypergranulation tissue. patient 1: a 76-year-old man presented to clinic for treatment of a squamous cell carcinoma measuring 2.1 x 2.3 cm on the medial parietal scalp. mohs micrographic surgery was done in one stage and the defect was repaired with a primary closure. the sutures were removed 12 days after surgery, and the wound had normal post-operative appearance. three weeks after mohs, the patient presented with pain at the surgical site. on review, the wound had dehisced and was covered with a yellow crust. bacterial culture revealed heavy growth of methicillin-susceptible staphylococcus aureus (mssa). the wound was gently debrided and covered with a hydrocolloid dressing and oil emulsion. the patient was instructed to clean the wound daily with soap and water and continue covering the wound with a hydrocolloid dressing. one month after the surgical procedure, the wound was noted to have developed exuberant granulation tissue. (figure 1a) the traditional method of treatment with pressure dressings was attempted. at this point, the patient was seen every 4 days for dressing changes and cleaning. the wound was also gently debrided with a curette three more times during the next month. approximately two months after mohs, during debridement the wound began to bleed. aluminum chloride was placed on the wound to achieve hemostasis. flurandrenolide 0.05% cream was applied, and then the wound was covered with a hydrocolloid dressing. on follow up, it was noted that the granulation tissue had improved significantly. (figure 1b) aluminum chloride was then applied weekly for a period of 4 weeks and until resolution. six weeks after its appearance, the granulation tissue had fully resolved. (figure 1c) patient 2: an 87-year-old man presented to clinic for removal of a squamous cell carcinoma measuring 2.0 x 2.0 cm on the medial parietal scalp. mohs micrographic surgery was performed, and the lesion was cleared in one stage. the defect was repaired with a primary closure. the sutures were removed 13 days after mohs, and the wound had a normal post-operative appearance. eleven days after suture removal, the patient presented to clinic with a surgical site infection that was draining purulent material. the wound was incised and drained. a bacterial culture revealed heavy growth of mssa. over the course of the eight weeks, the patient completed two courses of antibiotics, first minocycline 100 mg twice a day for five days and then dicloxacillin 500 mg twice a day for seven days. additionally, he was seen in clinic approximately every 4 days for wound checks and gentle debridement. wound care consisted of cleansing with soap and water, application of an oil emulsion dressing, and then hydrocolloid dressing. case report skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 334 figure 1. a) a 76-year-old man with evidence of hypergranulation tissue on the scalp after mohs micrographic surgery for squamous cell carcinoma. b) the patient’s hypergranulation tissue is resolving after an application of aluminum chloride. c) the patient’s scalp defect resolved entirely 10 weeks after the original mohs procedure. more than two months after mohs, the wound had not fully healed and hypergranulation tissue was noted. topical aluminum chloride was applied to the wound once, the wound was left open without a bandage, and then three weeks later the wound was closed. aluminum chloride is an effective hemostatic agent commonly used in dermatology. it is a readily available and low-cost option for use after dermatologic procedures such as biopsies.2 aluminum chloride is a caustic agent that is hydrolyzed by water to produce hydrated aluminum hydroxide and hydrochloric acid.3 this is thought to lead to vasoconstriction, tissue coagulation, and activation of the coagulation pathway.3 this protein coagulating effect induces tissue necrosis, eschar formation, and finally hemostasis.4 it also acts as an astringent to contract and retract the tissues it contacts.5 hypergranulation tissue is a highly vascular and friable tissue that responds to hemostatic agents by necrosing and involuting. aluminum chloride has an advantage over other hemostatic agents such as silver nitrate and ferric subsulfate because it is less likely to leave behind pigment particles that may stain the skin.4 as evidenced by the two cases reported, topical aluminum chloride is an effective treatment option for hypergranulation tissue. no adverse events were seen in our two patients, but given the lack of previous reports, further studies are needed to examine the side effect profile of this regimen. chronic wounds are a common treatment challenge for clinicians. they are expensive to treat, as they frequently do not respond to standard of care treatment modalities. due to its low cost and widespread availability, clinicians may consider topical aluminum chloride when managing post-surgical hypergranulation tissue. conflict of interest disclosures: none. funding: none. skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 335 corresponding author: giselle prado, md national society for cutaneous medicine, new york, ny drgiselleprado@gmail.com references: 1. 1) vuolo j. hypergranulation: exploring possible management options. br j nurs. 2010;19(6):s4, s68. 2. glick, jaimie b., ravneet r. kaur, and daniel siegel. "achieving hemostasis in dermatology-part ii: topical hemostatic agents." indian dermatology online journal 4.3 (2013): 172. 3. kitchens, craig s., et al. consultative hemostasis and thrombosis: expert consult-online and print. (541). elsevier health sciences, 2013. 4. nguygen th. hemostasis. in: robinson jk, hanke cw, sengelmann rd, siegel dm, editors. surgery of the skin: procedural dermatology. 1st ed. chap. 17. new york, london: elsevier mosby; 2005. pp. 245–58. 5. strassler, howard e., and leendert boksman. "tissue management, gingival retraction and hemostasis." oral health 101.7 (2011): 35. efficacy and safety of brodalumab in obese patients with moderate-to-severe plaque psoriasis abby s. van voorhees,1 sylvia hsu,2 boni elewski,3 shipra rastogi,4 robert j. israel5 1eastern virginia medical school, norfolk, va; 2temple university school of medicine, philadelphia, pa; 3university of alabama at birmingham school of medicine, birmingham, al; 4ortho dermatologics, bridgewater, nj; 5valeant pharmaceuticals north america llc, bridgewater, nj winter clinical dermatology conference hawaii® • january 12-17, 2018 • lahaina, hi introduction • brodalumab is a fully human anti–interleukin-17 receptor a (il-17ra) monoclonal antibody indicated for the treatment of moderate-to-severe plaque psoriasis1 • efficacy and safety of brodalumab were evaluated in a phase 3, multicenter, randomized, double-blind, placebo-controlled study (amagine-1)1 • there is a well-established association between psoriasis and obesity, with the risk of psoriasis directly related to body mass index (bmi)2,3 – risk estimate (95% ci) for psoriasis in those with bmi ≥30 kg/m2 was 1.9 (1.2-2.8), as determined from an analysis of an italian cohort3 • obese patients with psoriasis often experience decreased efficacy and increased susceptibility to certain side effects of therapeutic agents, making effective treatment in this population challenging2 objective • to evaluate the efficacy and safety of brodalumab in nonobese and obese patients with moderate-tosevere plaque psoriasis methods study design • efficacy and safety of brodalumab were investigated in a phase 3, multicenter, randomized trial of patients with moderate-to-severe plaque psoriasis (amagine-1) – patients were randomized to receive brodalumab 210 mg or placebo every 2 weeks (q2w) for 12 weeks – after 12 weeks, patients were re-randomized to receive brodalumab 210 mg q2w or placebo for up to 52 weeks • on the basis of bmi, patients were categorized as nonobese (bmi <30 kg/m2) or obese (bmi ≥30 kg/m2) • comparisons between nonobese and obese patients were made among patients who received continuous treatment with brodalumab 210 mg q2w through 52 weeks endpoints/assessments • skin clearance was monitored by the static physician’s global assessment (spga) and the psoriasis area and severity index (pasi) • safety was assessed by monitoring exposure-adjusted treatment-emergent adverse event (teae) rate per 100 patient-years results patient demographics and baseline disease characteristics • most patients were male, with an approximate mean (standard deviation) age of 45.8 (13.3) years for nonobese patients and 47.0 (12.4) years for obese patients (table 1) • of 659 total patients at baseline, 54.6% (n=360) were nonobese and 45.4% (n=299) were obese • weight and bmi were similar between the placebo and brodalumab groups within the nonobese and obese groups efficacy • in a post hoc comparison of patients receiving continuous brodalumab 210 mg q2w, rates of achieving spga score of 0 or 1 (spga 0/1), 75% improvement in pasi (pasi 75), pasi 90, and pasi 100 were higher among nonobese patients than obese patients at weeks 12 and 52 (figure) • the percentage of patients achieving pasi 100 increased from week 12 to week 52 in both nonobese and obese patients • obese patients had a larger increase in response rates of skin clearance as measured by spga 0/1, pasi 75, pasi 90, and pasi 100 from week 12 to week 52 compared with nonobese patients • at week 12, 2.3% (3/130), 3.1% (4/130), 1.5% (2/130), and 0.8% (1/130) of nonobese patients receiving placebo achieved spga 0/1, pasi 75, pasi 90, and pasi 100, respectively, compared with 0% (0/89), 2.2% (2/89), 0% (0/89), and 0% (0/89) of obese patients (data not shown) – among nonobese and obese patients randomized to the placebo group after week 12, none achieved spga 0/1, pasi 75, pasi 90, or pasi 100 at week 52 (data not shown) safety • through 52 weeks, 388.7 teaes per 100 patient-years were reported among nonobese patients continuously treated with brodalumab 210 mg q2w compared with 370.8 teaes per 100 patientyears among obese patients (table 2) table 1. baseline characteristics table 2. exposure-adjusted teae rates through week 52 figure. nonobese and obese patients who achieved (a) spga 0/1, (b) pasi 75, (c) pasi 90, and (d) pasi 100 at weeks 12 and 52. r es po nd er s, % 60 0 40 20 100 80 week 12 spga 0/1 86.8 99 69 63.9 week 52 86.7 78.9 a r es po nd er s, % 60 0 40 20 100 80 week 12 pasi 75 90.4 75.9 week 52 91.1 81.6 b r es po nd er s, % 60 0 40 20 100 80 week 12 pasi 90 80.7 59.3 week 52 84.4 71.1 c r es po nd er s, % 60 0 40 20 100 80 week 12 pasi 100 55.3 27.8 week 52 80.0 52.6 d nonobese obese 39 30 n n n n103 82 41 31 2036306327386492 pasi 75, 90, and 100, psoriasis area and severity index 75%, 90%, and 100% improvement; spga 0/1, static physician’s global assessment score of 0 or 1. acknowledgments: medical writing support was provided by medthink scicom and was funded by ortho dermatologics. this study was sponsored by amgen inc. author disclosures: the authors disclose past or current financial relationships with the following companies: van voorhees – abbvie, allergan, celgene, dermira, derm tech, novartis, and valeant pharmaceuticals north america llc; hsu – abbott, abbvie, amgen, biogen, centocor biotech, dermik, eli lilly, galderma, genentech, janssen biotech, medicis pharmaceutical, novartis, promius pharma, regeneron, sun pharmaceutical industries/ranbaxy, and valeant pharmaceuticals north america llc; elewski – abbvie, amgen, anacor, boehringer ingelheim, celgene, eli lilly, incyte, merck, novan, novartis, pfizer, sun pharmaceutical industries, valeant pharmaceuticals north america llc, and viamet; rastogi – ortho dermatologics and valeant pharmaceuticals north america llc; and israel – valeant pharmaceuticals north america llc. references: 1. papp et al. br j dermatol. 2016;175:273-286. 2. bremmer et al. j am acad dermatol. 2010;63:1058-1069. 3. naldi et al. j invest dermatol. 2005;125:61-67. conclusions • higher rates of skin clearance as assessed by spga and pasi were associated with brodalumab 210 mg q2w in nonobese vs obese patients • rates of complete skin clearance (pasi 100) increased in both nonobese and obese patients with longer duration of treatment with brodalumab 210 mg q2w (through 52 weeks) • the increase in response rate of skin clearance from week 12 to week 52 in obese patients was greater than that in nonobese patients, suggesting that response rate can be improved with longer treatment in obese patients nonobese obese placebo (n=130) brodalumab 210 mg q2w (n=114) placebo (n=89) brodalumab 210 mg q2w (n=108) age, mean (sd), y 47.4 (13.7) 44.7 (11.9) 46.1 (12.5) 48.0 (12.3) sex, n (%) male female 101 (77.7) 29 (22.3) 79 (69.3) 35 (30.7) 59 (66.3) 30 (33.7) 82 (75.9) 26 (24.1) weight, mean (sd), kg 78.6 (12.2) 75.7 (12.5) 107.2 (17.0) 108.0 (20.5) bmi, mean (sd), kg/m2 26.1 (2.6) 25.7 (2.9) 36.4 (5.8) 36.7 (7.2) bmi, body mass index; q2w, every 2 weeks; sd, standard deviation. n (r) nonobese (n=181) obese (n=164) all teaes 558 (388.7) 474 (370.8) all saes 10 (7.0) 17 (13.3) deaths 2 (1.4) 1 (0.8) infections fungal infections 174 (121.2) 7 (4.9) 149 (116.6) 11 (8.6) n, number of teaes; r, exposure-adjusted event rate per 100 patient-years (n/patient-year*100); sae, serious adverse event; teae, treatmentemergent adverse event. © 2017. all rights reserved. 7812_efficacy in obese populations_m1-3.indd 1 12/12/17 11:17 am sernivo poster 4 x 4. vr11 efficacy of a novel formulation of betamethasone dipropionate 0.05% spray versus augmented betamethasone dipropionate 0.05% lotion in patients ≥ 18 years of age with moderate plaque psoriasis: a pooled analysis all other trademarks are property of their respective owners. all rights reserved. objective methods results introduction ©2023 primus pharmaceuticals, inc. scottsdale, az 85253 to further assess the e�cacy of bds versus bdl in patients with moderate plaque psoriasis using pooled data from two phase 3 clinical trials. pooled e�cacy analysis included patients with stable disease (present for ≥ 3 months), an investigator global assessment (iga) = 3, and a body surface area (bsa) of 10-20% who received either bds (n = 356) or bdl (n = 90). e�cacy included the proportion of patients with success de�ned as an iga = 0 or 1 (none or minimal) and ≥ 2-grade improvement at day 15; the proportion of patients with a tss50 (total sign score improvement of at least 50%); the proportion of patients with a tss = 0 or 1 (clear or slight to mild) strati�ed by sign; and the relative proportion of patients receiving bds (within group) with a tss = 0 or 1 strati�ed by sign. statistical analysis included a fisher’s exact (2-tail) test for categorical data. success based on iga was greater for bds versus bdl at days 4 (2.2% versus 1.1%, p = 0.6941), 8 (11.5% versus 6.7%, p = 0.2480), and 15 (20.2% versus 18.9%, p = 0.8829), but not statistically signi�cant. the proportion of patients with a tss50 was greater for bds at days 4 (13.2% versus 5.6%, p = 0.0438), 8 (34.7% versus 29.2%, p = 0.3789), and 15 (51.0% versus 42.0%, p = 0.1523) with statistical signi�cance at day 4. the proportion of patients with a tss = 0 or 1 strati�ed by sign is presented in table 1. statistically signi�cant superiority was observed in patients receiving bds versus bdl for erythema at day 4, and scaling at days 4 and 15. within group (bds) comparisons for each tss sign are presented in table 2. the proportion of patients with a tss = 0 or 1 was statistically greater for scaling versus erythema and plaque elevation at all time points. success was similar between a novel mid-potent formulation of betamethasone dipropionate 0.05% spray (bds) and super-high potency augmented betamethasone dipropionate 0.05% lotion (bdl). patients receiving bds achieved greater treatment e�cacy regarding scaling than those receiving bdl. bds was most successful within group in the treatment of scaling versus erythema and plaque elevation. study 1 nct 01947491 n=394 randomized 4:2:2:1 study 2 nct 01967069 n=277 randomized 2:1 bds n=174 bdl n=90 vehicle spray n=87 vehicle lotion n=43 bds n=182 vehicle spray n=95 figure 1. trial designs references: 1. kircik l, okumu f, kandavilli s, sugarman j. rational vehicle design ensures targeted cutaneous steroid delivery. j clin aesthetic dermatol. 2017;10(2):12-19. 2. fowler jf, hebert aa, sugarman j. dfd-01, a novel medium potency betamethasone dipropionate 0.05% emollient spray,demonstrates similar e�cacy to augmented betamethasone dipropionate 0.05% lotion for the treatment of moderate plaque psoriasis. j drugs dermatol jdd. 2016;15(2):154-162. 3. sidgiddi s, pakunlu ri, allenby k. e�cacy, safety, and potency of betamethasone dipropionate spray 0.05%: a treatment for adults with mild-to-moderate plaque psoriasis. j clin aesthetic dermatol. 2018;11(4):14-22. 4. stein gold l, jackson jm, knuckles mlf, weiss js. improvement in extensive moderate plaque psoriasis with a novel emollient spray formulation of betamethasone dipropionate 0.05. j drugs dermatol jdd. 2016;15(3):334-342. conclusions linda stein gold md jonathan s. weiss md joseph f. fowler md adelaide a. hebert md jeffrey sugarman md henry ford health system, detroit, mi geogia dermatology partners and gwinnett clinical research center, inc., snellville, ga university of louisville, louisville, ky uthealth mcgovern medical school, houston, tx redwood dermatology research, santa rosa, ca this submission was supported by primus pharmaceuticals. sign day 4 day 8 day 15 erythema scaling plaque elevation success (0 or 1) success (0 or 1) success (0 or 1) 84/356 (23.6%) 141/356 (39.6%) 99/356 (27.8%) 169/346 (48.8%) 213/346 (61.6%) 177/346 (51.2%) 214/347 (61.7%) 254/347 (73.2%) 228/347 (65.7%) scaling vs erythema erythema vs plaque elevation scaling vs plaque elevation p-value[a] p-value[a] p-value[a] < 0.0001 0.2298 0.0011 0.0010 0.5946 0.0073 0.0016 0.3048 0.0392 table 2. bds within group: a pooled analysis of sign scores (itt population) [a] p-values derived from fisher's exact (2-tail) test. executed on 30dec22:13:06; sas (v9.4) success table 1. bds versus bdl: a pooled analysis of sign scores (itt population) sign study day success/failure bds bdl p-value[a] erythema baseline day 4 day 8 day 15 [a] p-values derived from fisher's exact (2-tail) test. executed on 30dec22:13:06; sas (v9.4) success (0 or 1) failure success (0 or 1) failure success (0 or 1) failure success (0 or 1) failure 8/356 (2.2%) 348/356 (97.8%) 84/356 (23.6%) 272/356 (76.4%) 169/346 (48.8%) 177/346 (51.2%) 214/347 (61.7%) 133/347 (38.3%) 1/90 (1.1%) 89/90 (98.9%) 11/90 (12.2%) 79/90 (87.8%) 34/89 (38.2%) 55/89 (61.8%) 48/88 (54.5%) 40/88 (45.5%) 0.6941 0.0206 0.0754 0.2255 scaling baseline day 4 day 8 day 15 success (0 or 1) failure success (0 or 1) failure success (0 or 1) failure success (0 or 1) failure 12/356 (3.4%) 344/356 (96.6%) 141/356 (39.6%) 215/356 (60.4%) 213/346 (61.6%) 133/346 (38.4%) 254/347 (73.2%) 93/347 (26.8%) 3/90 (3.3%) 87/90 (96.7%) 23/90 (25.6%) 67/90 (74.4%) 51/89 (57.3%) 38/89 (42.7%) 54/88 (61.4%) 34/88 (38.6%) 1.0000 0.0144 0.4680 0.0355 plaque elevation baseline day 4 day 8 day 15 success (0 or 1) failure success (0 or 1) failure success (0 or 1) failure success (0 or 1) failure 18/356 (5.1%) 338/356 (94.9%) 99/356 (27.8%) 257/356 (72.2%) 177/346 (51.2%) 169/346 (48.8%) 228/347 (65.7%) 119/347 (34.3%) 2/90 (2.2%) 88/90 (97.8%) 19/90 (21.1%) 71/90 (78.9%) 43/89 (48.3%) 46/89 (51.7%) 51/88 (58.0%) 37/88 (42.0%) 0.3915 0.2294 0.6369 0.2131 betamethasone dipropionate 0.05% spray (bds sernivo®, primus pharmaceuticals) is a novel mid-potent formulation indicated for the treatment of plaque psoriasis. in vitro testing has proven greater residence time for bds within the skin compared to super-high potency augmented betamethasone dipropionate 0.05% lotion (bdl diprolene®, organon).1 in two identically designed phase 3 trials, bds showed statistically signi�cant superiority over vehicle in both studies, and equivalence to bdl in study 1 in terms of treatment success.2-4 data from these two phase 3 trials have been pooled to further evaluate the e�ectiveness of bds versus bdl. disclosures: lsg investigator, advisor, and/or speaker for arcutis, dermavant, leo, ortho derm, p�zer, primus pharmaceuticals jsw research grants: almirall, dr. reddy’s lab, galderma, ortho, promius consulting: cutera, dr. reddy’s lab, epi health, galderma, novan, ortho, promius advisory boards: dr. reddy’s lab, galderma, ortho, promius jff consultant for primus pharmaceuticals; speaker and consultant for smartpractice, inc. aah research grants (paid to the medical school): p�zer, arcutis, abbvie, leo, xencor honoraria (advisory boards and lectures): p�zer, arcutis, leo, ortho dermatologics, incyte, almirall dsmb: ortho dermatologics, gsk, regeneron, sano� js consulting: galderma, incyte, sol-gel advisory boards: incyte, p�zer, sol-gel speaker: galderma, incyte, p�zer honoraria: galderma, incyte, sol-gel results • at 16 weeks during the first treatment cycle, a higher proportion of moderate and severe lesions at baseline treated with diacerein 1% ointment achieved treatment success, as compared with vehicle-treated lesions (58% vs 40%; p=.036) (figure 4) • similarly, at 16 weeks, the proportion of lesions treated with diacerein 1% ointment showing a 2-point reduction in iga score trended higher, as compared with vehicle-treated lesions (70% vs 47%; p=.067) (figure 5) figure 4. percentage of moderate and severe lesions achieving treatment success (iga 0/1 and a 2-point reduction) 58% 40% diacerein (n=76) placebo (n=58) -18 p er ce nt 100 80 60 40 20 0 70% 47% diacerein (n=76) placebo (n=58) -23 p er ce nt 100 80 60 40 20 0 p=.036 p=.067 • the mean absolute change in the iga score from baseline to the end of the follow-up period at 16 weeks was significantly greater for diacerein-treated lesions vs vehicle-treated lesions (2.4 vs 1.7; p=.001) • the mean iga for diacerein-treated lesions was significantly lower than that of vehicle-treated lesions at 16 weeks (1.08 vs 1.74; p=.004) (figure 6) figure 6. mean iga at each study visit (baseline, 4 weeks, 16 weeks) 3.49 2.54 1.08 3.43 2.79 1.74 0 1 2 3 4 m ea n ig a (s e m ) baseline 4 weeks 16 weeks p=.004 diacerein (n=76) placebo (n=58) diacerein (n=76) placebo (n=58) sem=standard error of the mean. • a reduction in blister counts positively correlated to improvements in overall disease severity (figure 7) figure 7. linear relationship between mean iga score and total blister counta m ea n ig a s co re total blister count pearson correlation coefficient=0.4855 (p=.001) m ea n ig a s co re total blister count pearson correlation coefficient=0.4855 (p=.001) conclusion • analysis of the phase 2 diacerein 1% ointment study demonstrated that more moderate or severe lesions achieved treatment success with diacerein than with placebo – treatment success was defined as the proportion of lesions resolving to iga 0 or 1 with a minimum 2-point reduction in the iga score • a reduction in blister counts positively correlated to improvements in overall disease severity • in addition, a significantly greater mean reduction in the iga score from baseline was achieved with diacerein as compared with placebo introduction • a phase 2 study of diacerein 1% topical ointment in patients with epidermolysis bullosa simplex (ebs) has demonstrated efficacy as compared with placebo with regard to blister count reduction • static scales that measure a clinician’s global impression of disease severity at a single time point are widely used in clinical trials for dermatological conditions and, although ebs scales exist in clinical practice, a standardized static scale for assessing ebs severity has yet to be developed • this report presents an analysis of data from the first treatment course and corresponding follow-up in the phase 2 crossover trial, was conducted to validate a novel, ebs-specific 5-point investigator’s global assessment (iga) scale based on efficacy data generated from the phase-2 study to measure the effects of diacerein 1% ointment vs vehicle control in the treatment of ebs analysis objectives • end points for the analysis of the phase 2 data were as follows: – primary end point was the proportion of patients with moderate to severe lesions who achieved “treatment success” at year 1 • treatment success was defined as an iga disease severity grade of 0 or 1 at visit 3 (week 16) with at least a 2-point reduction in the iga score, as compared with visit 2 (week 0) at year 1 • the χ2 test was used to determine the statistically significant difference between the diacerein 1% ointment and the control ointment treatment groups – additional end points included the proportion of patients from baseline to week 16 with a 2-pointreduction and the mean decrease in iga phase 2, randomized, controlled original study design • treatment in a 4-week intervention period, with a 3-month follow-up, was conducted in 2 successive years, with a cross-over of patients after the first year (figure 1) • secondary end points included the recurrence of blisters after a 12-week follow-up, a reduction of pain and pruritus, and quality of life measurements figure 1. diacerein 1% topical ointment for the treatment of ebs indication generalized, severe ebs primary objective reduction of blister numbers (by 40%) in the treated skin area (3% of body surface) vs placebo after 4 weeks study design cross-over design, randomized, double-blind, vehicle-controlled part 1: intervention phase for 4 weeks; part 2: 3-month follow-up study population generalized, severe ebs with k14 or k5 gene mutations, age 4-19 yr number of patients 17 therapy once-daily, self-application for 4 weeks study nurse visits time points for assessments year 1 4 weeks 3 months v0 t0 1 2 3 4 v1 v2 5 6 7 v3 follow-up follow-up diacerein placebo year 2 4 weeks 3 months v4 8 9 10 11 12 v5 v6 13 14 15 v7 follow-up follow-up diacerein placebo study nurse visits time points for assessments year 1 4 weeks 3 months v0 t0 1 2 3 4 v1 v2 5 6 7 v3 follow-up follow-up diacerein placebo year 2 4 weeks 3 months v4 8 9 10 11 12 v5 v6 13 14 15 v7 follow-up follow-up diacerein placebo original phase 2 efficacy at 4 and 16 weeks of year 1 • significantly more patients in the diacerein group achieved the primary end point of >40% reduction in blister numbers at both 4 weeks and at the end of the follow-up period at 16 weeks of year 1 (figure 2) figure 2. (a) proportion of patients with >40% reduction in blister numbers at 4 weeks (t4) and 3 months (t7). (b) representative images of improvements in lesions. 86% 100% 14% 57% t4 t7 p-values were calculated using a one-sided, bernard’s test for superiority. p er ce nt 100 80 60 40 20 0 p=.007 p=.038 diacerein placebo 86% 100% 14% 57% t4 t7 p-values were calculated using a one-sided, bernard’s test for superiority. p er ce nt 100 80 60 40 20 0 p=.007 p=.038 diacerein placebo iga scale for analysis • the iga is the investigator’s clinical assessment of the average overall severity of all ebs lesions, considered together, at a particular time point (table 1) table 1. investigator’s global assessment (iga) scale for ebs score definition 0 = clear no blisters, no erosions, minimal erythema and/or pigmentary changes may be present 1 = near clear 2 or fewer small blisters, faint signs of erosion may be present, barely perceptible evidence of crusting, slight erythema 2 = mild predominantly small and some medium blisters, minimal erosions, clear crusting, definite well-defined erythema 3 = moderate mix of small and medium blisters, definite erosions, limited areas of crusting, marked erythema 4 = severe mix of medium and large blisters, marked erosions, ulceration may be present, marked and extensive crusting, intense erythema methods for analysis • each photograph taken during the phase 2 blister-counting analysis study was labelled by patient id (1001-2011), visit number (0-7), and location to ensure a complete list of available areas for analysis • for patients with several affected locations in a sequence of visits, these locations were split into separate images to allow for independent analysis • photographs of the same location were displayed together on the same page, resulting in some pages with several photographs but one rating area. patients without images for all visits were not included in the iga analysis • following the organization of the photographs using this method, a 164page iga rating document was developed • each page contained a photograph (or photographs) of an affected location of a patient on the left side of the page and the iga rating scale on the right of the page, with a checkbox for the dermatologist to check, indicating the iga score that he or she assigned to the affected area (figure 3) please check box (✓) for appropriate iga score: 0 clear no blisters, no erosions, no crusting, minimal erythema and/or pigmentary changes may be present score definition 1 near clear 2 or fewer small blisters, faint signs of erosion may be present, barely perceptible evidence of crusting, slight erythema 2 mild predominantly small and some medium blisters, minimal erosions, clear crusting, definite well-defined erythema 3 moderate mix of small and medium blisters, definite erosions, limited areas of crusting, marked erythema 4 severe mix of medium and large blisters, marked erosions, ulceration may be present, marked and extensive crusting, intense erythema please check box (✓) for appropriate iga score: 0 clear no blisters, no erosions, no crusting, minimal erythema and/or pigmentary changes may be present score definition 1 near clear 2 or fewer small blisters, faint signs of erosion may be present, barely perceptible evidence of crusting, slight erythema 2 mild predominantly small and some medium blisters, minimal erosions, clear crusting, definite well-defined erythema 3 moderate mix of small and medium blisters, definite erosions, limited areas of crusting, marked erythema 4 severe mix of medium and large blisters, marked erosions, ulceration may be present, marked and extensive crusting, intense erythema figure 3. example of iga rating document layout • 10 leading dermatologists and eb experts from the us, europe, and australia were selected to blindly review and rate the photographs using the iga scale • each investigator was mailed a packet that contained instructions for the iga assessment project, an iga training manual, an iga rating document, and a prepaid return label and envelope • the photographs mailed to each dermatologist were randomly sorted during printing. thus, each dermatologist reviewed the same photographs • 10 investigators rated all photographs independently using the iga scale and reported the one integer that best described the average overall severity of all the ebs lesions considered together use of an investigator’s global assessment scale to evaluate disease severity in patients with epidermolysis bullosa simplex johann w. bauer1, amy paller2, jemima e. mellerio3, alain hovnanian4, john j. pan5, panagiotis zografos5, greg p. licholai5, and dedee f. murrell6 1department of dermatology, university hospital salzburg, paracelsus medical university, salzburg, austria; 2department of dermatology, northwestern university feinberg school of medicine, chicago, il, usa; 3department of pediatric and genetic dermatology, st. john’s institute of dermatology, guy’s and st. thomas’ nhs foundation trust, london, united kingdom; 4department of genetics, imagine institute, university paris descartes, paris, france; 5department of medical affairs, castle creek pharmaceuticals llc, parsippany, nj, usa, 6department of dermatology, st george hospital, and faculty of medicine, university of new south wales, sydney, australia reference bauer j. diacerein for the treatment of epidermolysis bullosa – a phase ii randomized, placebo controlled, double-blind multi-center clinical trial. presented at aad, 2017. figure 5. percentage of lesions with a 2-point reduction in iga score 58% 40% diacerein (n=76) placebo (n=58) -18 p er ce nt 100 80 60 40 20 0 70% 47% diacerein (n=76) placebo (n=58) -23 p er ce nt 100 80 60 40 20 0 p=.036 p=.067 athe correlation was between the total blister count and the mean (over lesions) iga score for the 14 patients who have the iga scores available. blister count data are available for each of the 3 timepoints (baseline, 4 weeks, and 16 weeks) for each of the 14 patients (n=42 timepoints) • danielle greenblatt, consultant dermatologist, department of pediatric and genetic dermatology, st. john’s institute of dermatology, guy’s and st. thomas’ nhs foundation trust, london, uk • anna bruckner, colorado children’s hospital, aurora, co, usa • aida lugo-somolinos, department of dermatology, university of north carolina chapel hill, nc, usa • joyce teng, stanford university department of dermatology, stanford, ca, usa • ena sokol, university medical center-groningen, the netherlands • john browning, texas dermatology and laser specialists research unit, san antonio, tx, usa • emily becker, texas dermatology and laser specialists research unit, san antonio, tx, usa • special thanks to sean kelly, operations manager at ccp, for his efforts in creating the rating document from randomized pictures, data collection and organization of source data files and preparing the results tables editorial support was provided by p-value communications. acknowledgments the authors wish to thank the following investigators who participated in the analysis project: start v0 2 weeks v1 4 weeks v2 4 months v3 p la c e b o d ia c e r e in a. b. skin july 2019 volume 3 issue 4 copyright 2019 the national society for cutaneous medicine 258 brief articles evaluation of cutaneous squamous cell carcinomas that extend to the parotid: the value of negative surgical margins brandon t. beal1 m.d., vamsi varra2 b.s., melinda b. chu3 m.d., eric s. armbrecht4 ph.d., ronald j. walker5,6 m.d., mark a. varvares7 m.d., scott w. fosko4,8,9 m.d. 1department of dermatology, cleveland clinic, cleveland, oh 2case western university school of medicine, cleveland, oh 3private practice, saint louis, mo 4saint louis university center for health outcomes research, saint louis university, saint louis, mo 5department of otolaryngology – head and neck surgery, saint louis university, saint louis, mo 6saint louis university cancer center, saint louis university, st. louis, mo 7department of otolaryngology, harvard medical school, boston, ma 8department of dermatology, mayo clinic, jacksonville, fl 9department of dermatology, saint louis university, saint louis, mo while high-risk characteristics for cutaneous squamous cell carcinoma (cscc) and the management of metastatic cscc have received considerable attention in the literature, standard of care management for the positive mms margin at the parotid fascia in cscc has yet to be clarified. the aim of this study is to better define optimal management approaches for the positive deep mohs micrographic surgery (mms) margin at the parotid fascia. inclusion criteria for this retrospective case series were patients presenting to the saint louis university with biopsy proven cscc with a positive deep mms margin at the parotid fascia who were referred to hns and treated with curative intent. the following data were recorded: age; gender; nccn high-risk factors; adjuvant surgical, medical, radiation (rt), or chemoradiation (crt) therapies; outcomes; and follow-up data. eight patients undergoing mms had a positive deep margin at the parotid fascia. hns performed 7 parotidectomies and 1 wide local excision (wle), obtaining negative margins in 75.0% (6/8) of patients (5/7 parotidectomies and 1/1 wle). obtaining negative surgical margins (6/8 patients) resulted in a disease free survival (dfs) and overall survival (os) of 27.8 and 43.6 months, respectively; compared to a dfs of 20.6 months and os of 39.1 months for positive margins (2/8 patients). this study demonstrates that resection with negative surgical margins results in excellent long-term local and regional disease control, and overall survival for cscc patients with positive deep mms margin at the parotid fascia. abstract skin july 2019 volume 3 issue 4 copyright 2019 the national society for cutaneous medicine 259 in 2012, approximately 700,000 new cases of cutaneous squamous cell carcinoma (cscc) were diagnosed in the us. of these, approximately 5,500 progressed to nodal metastasis and 4,000 caused death, highlighting the considerable burden of the disease.1 the preauricular area is a common site for cscc as well as a region of particular morbidity and mortality as it overlies the parotid gland containing cranial nerve vii.2 while high-risk characteristics for cscc and the management of metastatic cscc have received considerable attention in the literature, standard of care management for the positive mms margin at the parotid fascia in cscc has yet to be clarified.3 the aim of this study is to better define optimal management approaches for the positive deep mms margin at the parotid fascia. this retrospective case series was approved by the saint louis university institutional review board. initial inclusion criteria were all patients presenting to the saint louis university departments of dermatology and otolaryngology head and neck surgery (hns) with biopsy proven cscc treated with curative intent from january 1, 2000 to january 1, 2014. final inclusion criteria were patients with a positive deep mms margin at the parotid fascia who were referred to hns and treated with curative intent. the following data were recorded: age; gender; nccn high-risk factors; adjuvant surgical, medical, radiation (rt), or chemoradiation (crt) therapies; outcomes; and follow-up data. patient medical records and the social security death index were reviewed to determine disease-free survival (dfs) and overall survival (os), respectively. mms treated 325 patients with csccs in the preauricular, cheek, or temple anatomic regions. of these patients, 56 (17.2%, 56/325) were referred to hns for further evaluation. fifty-four patients had 1 cscc and 2 patients had 2 csccs. during individual chart review, 8 patients (2.5%, 8/325) undergoing mms had a positive deep margin at the parotid fascia. patients with a positive mms margin at the parotid fascia had a mean age of 77.1 years (range 57.2-90.2 years) and the majority were male (87.5%, 7/8). in this series, average tumor size was 2.8 cm (range 1.5 4.8 cm), 75.0% (6/8) were recurrent, and perineural invasion (pni) was present in 50.0% (4/8) of csccs (table 1). of note, 62.5% (5/8) of csccs were welldifferentiated and did not recur. two of eight csccs were noted to have keratoacanthoma (ka) features, one of which metastasized to the parotid gland (table 2). hns performed 7 parotidectomies and 1 wide local excision (wle), obtaining negative margins in 75.0% (6/8) of patients (5/7 parotidectomies and 1/1 wle). in the 2 patients who had positive margins after hns parotidectomies, rt was utilized (of note, 1 patient with positive margins after hns deferred parotidectomy several months until a palpable mass was found on physical exam). obtaining negative surgical margins (6/8 patients) resulted in a dfs and os of 27.8 and 43.6 months, respectively; compared to a dfs of 20.6 months and os of 39.1 months for positive margins (2/8 patients). for the entire cohort, dfs was 25.7 months and os was 42.5 months. 25.7 months and os was 42.5 months. introduction results methods skin july 2019 volume 3 issue 4 copyright 2019 the national society for cutaneous medicine 260 in this cohort, negative surgical margins improved dfs by 7.2 months and os by 4.5 months (table 1). negative surgical margins provide patients with high-risk cscc the best possible outcome, a definitive cure, and thus remains the treatment goal.4 mms remains the firstline treatment for high-risk cscc, as it provides thorough surgical margin evaluation, which allows a positive deep margin at the parotid fascia to be identified and further managed by hns.5 interestingly, the finding of a positive deep surgical margin led to the identification of microscopic disease in the parotid gland that was not detected with preoperative ct scans in two patients (table 2). this early detection of microscopic regional disease may have contributed to the improved outcomes observed in our cohort. when confronted with the positive deep mms margin at the parotid fascia, standard of care management has yet to be definitively defined. this finding has clear prognostic and therapeutic implications as involvement of the parotid has been associated with worse outcomes.2 patients with a positive deep margin at the parotid fascia should undergo hns evaluation and surgical management, as this is the most appropriate next step.5 surgical continuity of care, mms handing off a positive deep margin at the parotid fascia to hns, provides the patient the best opportunity to achieve negative surgical margins, and thus delivers the best possible outcome. clinicians have several options for treatment when the mms margin is positive at the parotid fascia, including hns excision, rt, crt, or a combination of hns excision and adjuvant rt or crt5. this study substantiates previous findings, further confirming the importance of obtaining negative surgical margins for cscc with parotid involvement.5 when negative surgical margins are unobtainable or there is lymph node involvement, surgery plus rt has been shown to be superior to either treatment modality individually.5 today, patients with highly locally invasive or metastatic disease would be candidates for the recently fda approved pd-1 inhibitor, cemiplimab.6 the limitations of this study include the following: it is a small retrospective case series and lacks randomization and blinding. a multi-institution prospective randomized control trial is needed to provide definitive evidence based standard of care management recommendations for high-risk and invasive cscc. discussion skin july 2019 volume 3 issue 4 copyright 2019 the national society for cutaneous medicine 261 table 1. patient demographics, tumor characteristics, and outcomes. variable n (%) mean range patient demographics: age, years 77.1 57.2 90.2 gender male 7 (88%) female 1 (13%) tumor characteristics size, cm 2.8 1.5 4.8 location cheek and temple 3 (38%) preauricular 5 (63%) recurrent tumors 6 (75%) primary tumors 2 (25%) histology well-differentiation 5 (63%) moderate-differentiation 3 (38%) keratoacanthomaa 2 (25%) acantholytic 1 (13%) perineural invasion 4 (50%) perineural inflammation 1 (13%) lymphovascular invasion 1 (13%) skin july 2019 volume 3 issue 4 copyright 2019 the national society for cutaneous medicine 262 abbreviations: hns, otolaryngology – head and neck surgery. atwo csccs had keratoacanthoma features. one was well-differentiated, and the other was moderatelydifferentiated and metastasized to the parotid gland. summary of outcomes entire cohort 8 (100) follow-up, months 23.1 0.0 64.4 disease-free survival 25.7 4.0 64.4 overall survival 42.5 15.0 85.0 negative margins after hns 6 (75%) disease-free survival 27.8 6.0 64.4 overall survival 43.6 16.0 85.0 positive margins after hns 2 (25%) disease-free survival 20.6 4.0 37.1 overall survival 39.1 15.0 63.2 skin july 2019 volume 3 issue 4 copyright 2019 the national society for cutaneous medicine 263 table 2. patient characteristics, management approaches, and outcomes. location/ size tumor features physical exam/ imaging/ consults surgical management disease-free survival/overall survival 1 left preauricular/2.6x1.4cm recurrent, pninv, welldifferentiated ct: negative. premms hns consult 1. slow mohsa: 1 stage. positive margin at parotid fascia. 2. hns: superficial parotidectomy and neck dissection. intraand peri parotid ln levels ii, iii, and v positive with ecs. margins negative. 3. adjuvant rt. dfs: 64.4mo / os: (cod unknown) 73.4mo 2 left preauricular /3.0x2.3cm recurrent s/p ln2; moderately differentiated with keratoacanthoma features, pninf; ct: negative 1. mms: 1 stage. positive margin at parotid fascia. 2. slow mohs: 2nd stage (excision processing). positive deep margin. 3. hns: parotidectomy. parotid gland positive; lns negative. positive margins. pt declined further surgery. 4. adjuvant rt (positive re-excision margins). dfs: 37.1mo/ os: currently alive, 63.2mo 3 right temple and cheek/2.2x1.6cm recurrent s/p 2 excisions; welldifferentiated, pninv, lymphovascular invasion; muscular invasion p/e: parotid mass. ct: positive 1. mms: 4 stages. positive margin at parotid fascia. 2. pt declined parotidectomy. 3. palpable mass noted on p/e during 2month f/u 4. hns: superficial parotidectomy and neck dissection. parotid gland and parotid lns positive with ecs. positive margin. 5. adjuvant rt (positive re-excision margins and to recurrence) dfs: 4mo (metastasis in subcarinal ln, received subsequent rt to chest)/ os: (cod unknown) 15mo 4 right preauricular/4.8x2.3cm welldifferentiated, acantholytic, pninv ct: parotid invasion. pre1. slow mohs: 1 stage. positive margin at parotid fascia. 2. hns: parotidectomy and neck dissection. parotid gland positive; dfs: 6mo /os: currently alive, 21mo skin july 2019 volume 3 issue 4 copyright 2019 the national society for cutaneous medicine 264 mms hns consult ln negative. margins negative. 5 left temple and cheek/1.5x1.0cm recurrent, moderatedifferentiation, pninv no imaging 1. slow mohs: 3 stage. positive margin at parotid fascia. 2. hns: re-excision, superficial parotidectomy, and neck dissection. parotid gland negative. margins negative. dfs: 20.8mo/ os: (cod unknown) 39.7mo 6 right preauricular/3.2x2.7cm moderatedifferentiation ct: negative 1. mohs: 6 stages. positive margin at parotid fascia. 2. hns: re-excision and parotidectomy. parotid gland negative. margins negative. dfs: 9.6mo/ os: (cod unknown) 26.4mo 7 left preauricular/3.3x2.1cm recurrent s/p ed&c and excision, welldifferentiated with keratoacanthoma features no imaging 1. slow mohs: 1 stage. positive margin at parotid fascia. 2. hns: re-excision and superficial parotidecomy. parotid gland negative. margins negative. dfs: no followup/ os: (cod unknown) 16mo 8 right temple and cheek/ 2.0x2.0cm recurrent, welldifferentiated no imaging 1. slow mohs: 1 stage. positive deep margin. 2. hns: re-excision. margins negative. dfs: 38.0mo/ os: currently alive, 85 mo abbreviations: pninv, perineural invasion; ct, computed tomography; mms, mohs micrographic surgery, frozen sections only; hns, otolaryngology-head and neck surgery; ecs, extracapsular spread; rt, radiation therapy; dfs, disease-free survival; os, overall survival; cod, cause of death; ln2, liquid nitrogen; pninf, perinerual inflammation; ed&c, electrodessication and curettage. aslow mohs: mms with staged excision pathology; permanent sections only. bpatient differed parotidectomy until parotid swelling was found on physical exam during follow-up. local and distant metastases were noted on computed tomography scan. skin july 2019 volume 3 issue 4 copyright 2019 the national society for cutaneous medicine 265 this study and others demonstrate that resection with negative surgical margins results in excellent long-term local and regional disease control, and overall survival for patients with high-risk and invasive cscc.4 when caring for complex patients with invasive cscc we utilize an early, collaborative, and multidisciplinary approach with hns that includes the concept of surgical continuity of care. surgical continuity of care means when managing the mms positive deep margin we collaborate closely with hns in an attempt to obtain negative surgical margins prior to rt, crt, or other treatment modalities when treating patients with curative intent. tumor free surgical margins remain the treatment goal for invasive and locoregional cscc, because a clear surgical margin provides the best outcome for our patients. conflict of interest disclosures: none. funding: none. corresponding author: brandon t. beal, m.d. department of dermatology cleveland clinic cleveland, ohio bealb@ccf.org references: 1. karia ps, han j, schmults cd. cutaneous squamous cell carcinoma: estimated incidence of disease, nodal metastasis, and deaths from disease in the united states. j am acad dermatol. 2013;68(6):957-66. 2. veness mj, porceddu s. palme ce, morgan gj. cutaneous head and neck squamous cell carcinoma metastatic to parotid and cervical lymph nodes. head neck. 2007 jul;29(7):621-31. 3. que skt, zwald fo, schmults cd. cutaneous squamous cell carcinoma: management of advanced and highstage tumors. j am acad dermatol. 2018;78(2):249-261. 4. stewart tj, saunders a. risk factors for positive margins after wide local excision of cutaneous squamous cell carcinoma. j dermatolog treat. 2018:1-3. 5. fu t, aasi sz, hollmig st. management of high-risk squamous cell carcinoma of the skin. curr treat options oncol. 2016;17(7):34. 6. migden mr, rischin d, schmults cd, guminski a, hauschild a, lewis kd, chung ch, hernandez-aya l, lim am, chang als, rabinowits g, thai aa, dunn la, hughes bgm, khushalani ni, modi b, schadendorf d, gao b, seebach f, li s, li j, mathias m, booth j, mohan k, stankevich e, babiker hm, brana i, gil-martin m, homsi j, johnson ml, moreno v, niu j, owonikoko tk, papadopoulos kp, yancopoulos gd, lowy i, fury mg. pd-1 blockade with cemiplimab in advanced cutaneous squamous-cell carcinoma. new england journal of medicine. 2018;379(4):341-351. conclusion file:///c:/users/vladimir%20prado/appdata/local/temp/temp1_archive.zip/bealb@ccf.org poster presented at the 25th eadv congress, vienna, austria, 28 september – 2 october 2016 calcipotriol plus betamethasone dipropionate foam is effective in patients with moderate-to-severe psoriasis: post-hoc analysis of the pso-able study carle paul,1 craig leonardi,2 alan menter,3 kristian reich,4 linda stein gold,5 richard b warren,6 anders møller,7 mark lebwohl8 1paul sabatier university and larrey hospital, toulouse, france; 2st louis university school of medicine, st louis, mo, usa; 3baylor university medical center, dallas, tx, usa; 4dermatologikum hamburg and sciderm gmbh, hamburg, germany; 5henry ford health system, detroit, mi, usa; 6dermatology centre, university of manchester, manchester, uk; 7leo pharma a/s, ballerup, denmark; 8icahn school of medicine at mount sinai, new york, ny, usa introduction ● most guidelines recommend that mild-to-moderate psoriasis be treated with topical therapies.1,2 use of topical therapies in severe/extensive psoriasis is not generally recommended ● ointment and gel formulations of fixed combination calcipotriol 50 μg/g (cal) plus betamethasone 0.5 mg/g (bd) are established first-line topical treatments.3 a foam formulation has been developed with the aim of enhancing adherence and increasing the therapeutic options available ● studies with cal/bd foam have demonstrated greater in vitro drug penetration and a greater antipsoriatic effect over 4 weeks of treatment than cal/bd ointment and vehicle, with a comparable tolerability profile4–7 ● the phase iii pso-able study (nct02132936) in patients with mild-to-severe psoriasis demonstrated that cal/bd foam had superior efficacy at week 4 compared with cal/bd gel at week 8 (based on the recommended treatment periods in the approved labels)8 ● this analysis from pso-able assesses the efficacy of cal/bd foam and gel in the subgroup of patients with moderate-to-severe psoriasis materials and methods pso-able study design ● prospective, multicentre, investigator-blinded ● patients were randomized 4:4:1:1 to once-daily cal/bd foam, cal/bd gel, foam vehicle or gel vehicle for up to 12 weeks8 patients ● aged ≥18 years with mild-to-severe psoriasis according to the physician’s global assessment of disease severity (pga), involving 2–30% body surface area (bsa), and a modified (excluding the head, which was not treated) psoriasis area and severity index (mpasi) of ≥2 ● for inclusion in this subgroup analysis, a patient was required to have ‘moderate-to-severe’ psoriasis based on the ‘rule of tens’9: – bsa affected ≥10% or mpasi score >10 or dermatology life quality index (dlqi) score >10 assessments and endpoints ● efficacy was assessed at weeks 4, 8 and 12 by calculating: – proportion of patients achieving a ≥75% or ≥90% reduction in mpasi – change from baseline in bsa affected – proportion of patients who were clear/almost clear of psoriasis, with a ≥2 grade improvement according to pga (defined as ‘treatment success’) ● patients completed the dlqi questionnaire at baseline and weeks 4, 8 and 12 (range 0–30). quality of life was assessed by calculating the proportion of patients achieving: – dlqi score of 0/1 (ie no impact of psoriasis on the patient’s life) – decrease in dlqi score of ≥5 (ie the minimal clinically important difference) ● the amount of each product used throughout the study was also assessed statistical analysis ● analyses were conducted on the full analysis set, which comprised all patients with moderate-to-severe psoriasis ● last observation carried forward (locf) was used to impute values for missing mpasi data. an observed case approach was used for other variables ● this subgroup analysis demonstrates that cal/bd foam is effective in patients with moderate-to-severe psoriasis; it should be noted however, that it is difficult to treat psoriasis patients who have large bsa involvement purely with topical therapy. the superior efficacy of cal/bd foam over cal/bd gel that was observed in the primary pso-able study was maintained for up to 12 weeks 8 in these patients ● potential limitations of this analysis: the definition of moderate-to-severe (based on the ‘rule of tens’9) differs from that used in studies of systemic therapies, where patients are typically required to have bsa ≥10% and pasi >10; mean bsa, mpasi score and dlqi scores in this study were close to 10, therefore on the threshold for moderate-to-severe psoriasis ● this subanalysis suggests cal/bd foam may be a costsaving alternative to systemic therapies, in some patients with moderate-to-severe psoriasis who are able to maintain adherence to topical therapy and do not want to be exposed to systemic therapy conclusions results patients ● 463 patients were randomized to cal/bd foam (n=185), cal/bd gel (n=188), foam vehicle (n=47) and gel vehicle (n=43) seventy-seven cal/bd foam patients and 82 cal/bd gel patients – were classified as having moderate-to-severe psoriasis (table 1) acknowledgements this study was sponsored by leo pharma. medical writing support was provided by andrew jones, phd, from mudskipper business ltd, funded by leo pharma references 1. menter a et al. j am acad dermatol 2009;60:643–659. 2. nast a et al. arch dermatol res 2012;304:87–113. 3. laws pm & young hs. expert opin pharmacother 2010;11:1999–2009. 4. hollesen basse l et al. j invest dermatol 2014;134:s33:abst 192. 5. koo j et al. j dermatolog treat 2016;27:120–127. 6. leonardi c et al. j drugs dermatol 2015;14:1468–1477. 7. queille-roussel c et al. clin drug investig 2015;35:239–245. 8. paul c et al. j eur acad dermatol venereol 2016;in press. 9. finlay ay. br j dermatol 2005;152:861–867. 60 (a) (b) 50 40 20 30 10 0 week 4 week 8 week 12 cal/bd foam (n=77) cal/bd gel (n=82) pa ti en ts a ch ie vi ng m pa si 75 (% ) 30 25 15 20 10 5 0 week 4 week 8 week 12 pa ti en ts a ch ie vi ng m pa si 90 (% ) 40.3 17.1 53.2 22.0 57.1 35.4 11.7 2.4 27.3 8.5 15.6 12.2 figure 1. proportion of patients with moderate-to-severe psoriasis achieving (a) mpasi75 and (b) mpasi90 (locf) 100 80 60 40 20 0 baseline week 4 week 8 week 12 n=77cal/bd foam n=75 n=73 n=71 n=82cal/bd gel cal/bd foam cal/bd gel n=79 n=77 n=76 ch an ge in b sa a � ec te d (% ) figure 2. reduction in bsa affected by psoriasis from baseline in moderate-to-severe patients (observed cases) 40 35 30 20 25 10 15 5 0 week 4 week 8 week 12 cal/bd foam cal/bd gel pa ti en ts a ch ie vi ng tr ea tm en t s uc ce ss (% ) n=75 n=79 n=73 n=77 n=71 n=76 32.0 19.0 35.6 16.9 38.0 31.6 figure 3. proportion of moderate-to-severe patients achieving treatment success during treatment (observed cases) 60 50 40 20 30 10 0 week 4 week 8 week12 cal/bd foam cal/bd gel pa ti en ts a ch ie vi ng d lq i s co re of 0 o r 1 (% ) n=74 n=78 n=73 n=74 n=70 n=76 33.8 14.1 42.5 28.4 55.7 29.3 figure 4. proportion of patients achieving a dlqi score of 0/1 (observed cases) table 1. patient demographics and disease characteristics at baseline cal/bd foam (n=77) cal/bd gel (n=82) males:females, n 49:28 47:35 age, years 53.2 ± 12.9 52.1 ± 14.8 bsa, % 10.9 ± 6.8 10.4 ± 6.4 mpasi score 10.2 ± 5.2 8.9 ± 4.0 dlqi score 10.4 ± 5.7 12.0 ± 6.4 note: all data are mean ± standard deviation (sd) mpasi scores ● the proportion of patients achieving mpasi75 and mpasi90 was greater with cal/bd foam than cal/bd gel at weeks 4, 8 and 12 (figure 1) – percentage mean (± sd) reduction in mpasi from baseline to week 12 was 66.8 ± 37.6% with cal/bd foam and 57.7 ± 34.4% with cal/bd gel bsa affected by psoriasis ● the proportion of bsa affected decreased throughout treatment in both cal/bd foam and cal/bd gel groups (figure 2) – percentage mean (± sd) reduction from baseline to week 12 was 50.2 ± 43.0% with cal/bd foam and 39.2 ± 37.7% for cal/bd gel treatment success ● treatment success rates increased throughout the first 6 weeks, reaching 32.0% by week 4 in the cal/bd foam group; these rates continued to increase up to week 12 (figure 3) success rates were higher with cal/bd foam than cal/bd gel at – each time point dlqi scores ● a greater proportion of patients achieved a dlqi of 0/1 at weeks 4, 8 and 12 with cal/bd foam than cal/bd gel (figure 4) ● the proportion of patients achieving a decrease in dlqi of ≥5 with cal/bd foam was greater than with cal/bd gel at week 4 (70.3% vs 56.4%), then similar at weeks 8 (68.5% vs 66.2%) and 12 (62.9% vs 64.0%) amount of product used ● the mean amount of cal/bd foam used was 28.0 ± 20.3 g/week, compared with 22.6 ± 18.1 g/week of cal/bd gel the greatest usage of cal/bd foam occurred in the first 6 weeks– pcg-workstation-2 sticky note marked set by pcg-workstation-2 pcg-workstation-2 sticky note marked set by pcg-workstation-2 pcg-workstation-2 sticky note marked set by pcg-workstation-2 pcg-workstation-2 sticky note marked set by pcg-workstation-2 pcg-workstation-2 sticky note marked 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the national society for cutaneous medicine 7 original research a novel hydrocortisone-ethanol gel ointment for treating atopic dermatitis in children: a double blind, randomized, controlled clinical trial dale l pearlman, md1 1orliderm inc., menlo park, ca atopic dermatitis (ad) affects 17% of children1 and 7% of adults in the usa2. moderate to severe ad disrupts the lives of children and their families3. current therapies’ success is limited by low efficacy (40-60%), long duration of treatment (3-12 weeks4,5) and parental concerns about treatment safety. they worry antibiotics may cause antibiotic resistant bacteria6. more than 50% of patients (or their caregivers) turn to alternative (complementary) therapies because of these concerns7. a key component of ad therapy is directed at suppressing bacteria. staphylococcus aureus is a primary trigger of the inflammatory changes in ad. patients with atopic dermatitis are colonized by extremely high levels of staphylococcus aureus8. the patients have elevated levels of ige directed introduction importance: current treatments for moderate to severe atopic dermatitis (ad) in children are limited by incomplete efficacy, long time to benefit, and parental concerns about safety. this study evaluated a novel ointment for treating ad containing 1% hydrocortisone and 17% dispersed ethanol gel micro bubbles. observations: 20 children with moderate to severe ad participated in a one-week double blind, randomized, and controlled clinical trial. they were randomly assigned to apply bid either an ointment with 1% hydrocortisone ointment (hc) or a novel ointment containing 1% hydrocortisone and dispersed ethanol gel droplets (hc-eg). the primary endpoint was superiority of hc-eg over hc ointment in scorad score improvement during therapy. a secondary endpoint was improvement in pruritus score during therapy. both the primary and secondary endpoints were reached in this study. scorad score improved 74% on average with hc-eg ointment vs 41% with hc ointment (p=.02). pruritus score improved 68% on average with hc-eg ointment vs 37% with hc ointment (p=.009). no toxicity requiring stopping therapy was observed in either treatment group. conclusions and relevance: in this small controlled study hc-eg ointment was superior to hc ointment both in improving visible rash and pruritus of ad. parents felt hc-eg ointment was safe because it contains no prescription corticosteroids, prescription immunosuppressants, or antibiotics. independent, larger studies would be a next step in evaluating further this new way to treat ad. abstract skin january 2019 volume 3 issue 1 copyright 2018 the national society for cutaneous medicine 8 against staphylococcal cell surface proteins9. oral antibiotics, topical antibiotics, and bleach baths are often used to treat ad10. a novel antibacterial strategy could be topical application of alcohol-based hand sanitizer gel (abhsg). such gels contain 62-70% ethanol and are reported to be 99.999% effective against staphylococci11. children under the age of six years old may use abhsg’s if an adult supervises the application12. one cannot directly apply abhsg to eczematous skin because of stinging. while there is evidence that ethanol in solution with hydrocortisone does enhance delivery of the hydrocortisone across the skin13, we could find no report in the literature when the ethanol is in the form of gel microbubbles dispersed in an ointment. to use abshg in topical therapy of ad we needed to develop a new topical formulation which would prevent stinging, block possible absorption of ethanol and hydrocortisone across eczematous skin, and avoid exacerbating skin dryness. the novel ointment contains the ethanol in the form of dispersed abhsg microbubbles. the dispersion minimizes stinging and absorption. skin dryness is avoided by using an ointment vehicle and because abhsg contains moisturizers. trial design this is a double blind, randomized, controlled trial design in which neither the principle investigator (pi), patients, nor parents know whether hc or hc-eg ointment is used. patients are randomly assigned to a treatment group. patients have a pre-therapy visit and an end-therapy visit. at each visit the pi determines a modified scorad score based on surface area affected and the degree of redness, scaling, oozing/crusting, swelling, and excoriations. at each visit the parents score the pruritus in the preceding 24 hours on a 0 to 10 point scale. at the endtherapy visit parents are asked about local stinging with treatment, any change in skin color (blanching) where the ointment is applied, and signs of ethanol intoxication. participants written informed consent to participate and for photographs was obtained from the parents of the children participating. all photographs maintain the anonymity of the participant. no compensation was paid for participation. an independent irb function was provided by a group of pediatricians at a local multispecialty clinic. they reviewed and approved the study design. the principles outlined in the declaration of helsinki were followed. criteria for entry: 1) at the initial visit crusted and oozing lesions on some or all of these areas: trunk, limbs, and face. 2) history of inadequate response to prior used over-the counter ointments as well as to one or more of the following prescription medications: topical corticosteroids, topical calcineurin inhibitors, and topical and oral antibiotics. 3) age 3 months and older. intervention the test ointments were pre-formulated for dispensing. a) hc ointment: aquaphor® and corticosteroid 2.5% ointment in a ratio to yield 1% concentration of hydrocortisone. b) hc-eg ointment: aquaphor®, corticosteroid 2.5% ointment, and 70% methods skin january 2019 volume 3 issue 1 copyright 2018 the national society for cutaneous medicine 9 ethanol gel in a ratio to yield 1% hydrocortisone and 17% by volume ethanol gel. treatment patients applied at home a saturating dose of the assigned ointment to the affected areas bid for a week. a “saturating dose” meant apply ointment until no more will absorb and then wipe off the excess with a paper towel. during the clinical trial the only allowed topical treatment was the assigned ointment. the only oral therapy allowed was prn use of prior used oral antihistamines. outcomes the primary endpoint was superiority in average scorad improvement in patients treated with hc-eg ointment vs hc ointment. secondary endpoints were: 1. pruritus: superiority of hc-eg ointment vs hc ointment in average reduction in pruritus score. 2. enhanced corticosteroid absorption: lack of difference in skin blanching between the two treatment groups. 3. adverse effects local: stinging at time of application 4. adverse effects systemic: symptoms of ethanol intoxication: lack of difference in symptoms of mental confusion, slurred speech, and difficulty walking between the two groups. 5. parental concern about the safety of the medication. recruitment 20 patients were recruited from the local pediatricians who had reviewed and approved the study protocol. all 20 patients were available at the initial and end therapy visit. age ranged from 3 months to 12 years. primary endpoint: average scorad improved 74% in the hceg ointment treated patients vs 41% in the hc ointment treated patients. this is a statistically significant difference with p=.02 (table 1). these data are especially interesting in that they demonstrate that hc-eg ointment is better at treating more severe cases than hc ointment is at treating milder cases. by random assignment in this study, the patients table 1: change in scorad score in 20 patients with moderate to severe atopic dermatitis randomly assigned to apply for one week twice daily either 1% hydrocortisone (hc) ointment or 1% hydrocortisone ointment-ethanol gel (hc-eg). average scorad score 10 patients using hc ointment 10 patients using hc-eg ointment pre-treatment 28.9 42.1 end-treatment 17.1 10.9 average change pre to end treatment -40.8%* -74.2%* *statistically significant different between hc and hceg ointment group p=0.02. table 2: change in pruritus score in 20 patients with moderate to severe atopic dermatitis randomly assigned to apply either for one week twice daily 1% hydrocortisone (hc) ointment or 1% hydrocortisone ointment-ethanol gel (hc-eg) ointment. average pruritus score (0-10) 10 patients used hc ointment twice daily 10 patients used hc-eg ointment twice daily pre-treatment 6.1 6.1 end-treatment 4.1 1.95 % improvement 37%* 68%* *statistically significant different between hc and hceg ointment group p=0.009. results skin january 2019 volume 3 issue 1 copyright 2018 the national society for cutaneous medicine 10 that used hc-eg ointment turned out to be a more severe group than the group who received hc ointment. at entry into the study the patients assigned to hc-eg ointment had a worse average score than the hc ointment group (42.1 vs 28.9). despite starting with a worse average scorad at entry, the hc-eg ointment cohort ended treatment with a better average scorad score at the end of therapy (scorad of 10.9 with hc-ed ointment vs 17.1 with hc ointment) for examples of the degree of improvement with the hc-eg vs hc ointment see figure 1 and figure 2. secondary endpoints: pruritus: average score was 68% improved in the hc-eg ointment treated patients vs 37% in the hc ointment treated patients. this is a statistically significant difference with p=0.009 (table 2). stinging: one of ten of the hc-eg ointment treated patients experienced mild to moderate stinging when the ointment was applied. the remaining 9 patients and all the hc ointment patients reported no stinging. the stinging was relieved and the patient continued treatment by first applying a layer of aquaphor® and then the ointment for the first two days of therapy. after day two of therapy no further pre-application of aquaphor was needed. local corticosteroid effects via percutaneous absorption on eczematous skin: no patient in either cohort exhibited local blanching at the post-therapy examination or parent reported seeing blanching during treatment at home. evidence of systemic ethanol effect via percutaneous absorption on eczematous skin: none of the treated patients in the study figure 1: a patient with atopic dermatitis behind the knee randomized to treatment with hc ointment. a) before treatment. b) after 1 week of hc ointment. figure 2: another patient with more severe atopic dermatitis behind the knee randomized to treatment with hc-eg ointment. a) before treatment. b) after 1 week of 1% hc-eg therapy. a b a b skin january 2019 volume 3 issue 1 copyright 2018 the national society for cutaneous medicine 11 evidenced at end-therapy exam or was reported by parents during home therapy to have mental confusion, impaired balance, unsteady walking, or other signs of inebriation. concerns of patients about the safety of the study medications: all said they felt safe and comfortable about the ingredients in the study ointments and using them as directed to treat the ad. limitations of this study include the small sample size and the potential bias by the principle investigator due to conflict of interest. in this study we hypothesized that the dispersed ethanol gel microbubbles in the hydrocortisone ointment would increase efficacy by suppressing the eczematous skin’s staphylococcal population. while this study showed the anticipated increased clinical efficacy, the antibacterial basis for the improvement was not investigated in this trial. we did not measure the change in the staphylococcal biofilm population before and after treatment. thus further study will be needed to assess evaluate this hypothesized mechanism of action. in these patients with moderate to severe ad, 1% hydrocortisone-ethanol gel (hc-eg) ointment was superior to 1% hydrocortisone ointment (hc) in both objective improvement and reduction in pruritus. local irritation was minimal and easily managed. no systemic signs of ethanol intoxication occurred. parents reported their preference for hc-eg because of its rapid efficacy and being free of prescription corticosteroids and antibiotics. this is significant as parental noncompliance due to safety concerns can interfere with treatment.14,15 conflict of interest disclosures: the principle investigator and article author is the inventor and holds patents on this new technology. funding: none. corresponding author: dale l. pearlman, md orliderm inc. menlo park, ca md@dpearlman.biz acknowledgements: jade marcos provided principle administrative support for conducting this study. other members of my staff who also provided administrative support during this study: valerie santos, gianna panlasigui, linda vien, and elana naderzad, harry morewitz ph.d. provided extensive review of the literature as well as analysis of the physical chemistry aspects of the formulation. myra morewitz provided editorial guidance in this manuscript. references: 1. carbone a, siu a, and patel r, “pediatric atopic dermatitis: a review of the medical management”, ann pharmacother 2010;44:1448-58. 2. silverberg ji and greenland p, “eczema and cardiovascular risk factors in 2 us adult population studies “, journal of allergy and clinical immunology, 2015(135) 3, pages 721-728. 3. national institute for health and care excellence, “atopic eczema in children: management of atopic eczema in children from birth up to the age of 12 years”, www.nice.org.uk/nicemedia/pdf/cg057f ullguideline.pdf (accessed2009 march 15) 4. vernon hj, lane at, and weston w, “ comparison of mometasone furoate 0.1% cream and hydrocortisone 1.0% cream in the treatment of childhood atopic dermatitis”, jaad 1991;24:603-7. 5. huang jt, abrams m, tlougan b, et al, treatment of staphylococcus aureus discussion mailto:dalepearlmanmd@orliderm.com skin january 2019 volume 3 issue 1 copyright 2018 the national society for cutaneous medicine 12 colonization in atopic dermatitis decreases disease severity, pediatrics 2009;123;e808. 6. kojima r1, fujiwara t, matsuda a, narita m, matsubara o, nonoyama s, ohya y, saito h, matsumoto k, factors associated with steroid phobia in caregivers of children with atopic dermatitis, pediatr dermatol. 2013 jan-feb;30(1):29-35. 7. simpson el, basco m, hanifin j, a crosssectional survey of complementary and alternative medicine use in patients with atopic dermatitis, am j contact dermat. 2003 sep;14(3):144-7. 8. cho s-h, strickland i, boguniewicz m, et al. fibronectin and fibrinogen contributes to the enhanced binding of s. aureus to atopic skin. j allergy clin immunol 2001;108:269–74. 9. zollner tm, wichelhaus ta, hartung a, von mallinckrodt c, wagner to, brade v, et al. colonization with superantigenproducing staphylococcus aureus is associated with increased severity of atopic dermatitis. clin exp allergy 2000;30: 994-1000. 10. jennifer th, melissa a, brook t, rademaker, and paller as, “treatment of staphylococcus aureus colonization in atopic dermatitis decreases disease severity” pediatrics. 2009 may;123 (5):2008-2217. 11. hall ts, wren mw, jeanes a, and gant va, “a comparison of the antibacterial efficacy and cytotoxicity to cultured human skin cells of 7 commercial hand rubs and xgel, a new copper-based biocidal hand rub”, am j infect control. 2009 may;37(4):322-6. doi: 10.1016/j.ajic.2008.09.011. epub 2008 dec 31. 12. us department of health and human services, household products database, http://householdproducts.nlm.nih.gov/cgi bin/household/brands?tbl=brands&id=70 05062 accessed 09/05/2015. 13. liu p, kurihara-bergstrom t, good, cotransport of estradiol and ethanol through human skin in vitro: understanding the permeant/enhancer flux relationship, wrpharm res. 1991 jul;8(7):938-44. 14. hon kl1, kam wy, leung tf, lam mc, wong ky, lee kc, luk nm, fok tf, ng pc, steroid fears in children with eczema. acta paediatr. 2006 nov;95(11):1451-5. 15. kojima r1, fujiwara t, matsuda a, narita m, matsubara o, nonoyama s, ohya y, saito h, matsumoto k, factors associated with steroid phobia in caregivers of children with atopic dermatitis, pediatr dermatol. 2013 jan-feb;30(1):29-35. statistical analysis • proportions of patients who achieved a 75% or 90% improvement from baseline in pasi (pasi 75 or pasi 90), a physician’s global assessment score of 0 or 1 (pga 0/1), dermatology life quality index (dlqi) 0/1 through 128 weeks of treatment with czp 400 mg q2w (weeks 16–144 of the study) are reported. • responder rates in the subset of patients who achieved a pasi 75 response following 16 weeks of treatment with czp 400 mg q2w in the escape arm are also reported. • estimates of responder rate were based on the simple average response. patients mandatorily withdrawn from the study were treated as non-responders at subsequent timepoints; all other missing data were imputed using markov chain monte carlo (mcmc) methodology. results patient population and baseline characteristics • 116 patients did not achieve pasi 50 after 16 weeks of placebo treatment and entered the open-label czp 400 mg q2w escape arm. baseline demographics of these patients are shown in table 1. response to czp treatment • patients demonstrated a rapid response during the first 16 weeks of czp 400 mg q2w treatment; 74.7% of patients achieved pasi 75 at week 32, 48.7% achieved pasi 90, and 65.4% achieved pga 0/1 (figure 2a). • initial responder rates were sustained to week 144 (figure 2a). • similar trends were observed for dlqi 0/1 (figure 2b). maintenance of response • of the 82 patients who achieved pasi 75 after 16 weeks of czp 400 mg q2w treatment (week 32): – the majority (82.4%) maintained pasi 75 over a further 112 weeks of treatment (figure 3a) – 65.9% also achieved pasi 90 at week 32, and this value was maintained to 64.4% at week 144 (figure 3a) – 61.0% also reported dlqi 0/1 at week 32, which increased to 68.0% at week 144 (figure 3b) conclusions czp dosed at 400 mg q2w offers a durable, long-term treatment option for patients with moderate to severe pso. synopsis patients with moderate to severe plaque psoriasis were treated with certolizumab pegol dosed at 400 mg every two weeks for up to 128 weeks. patients demonstrated a rapid response in the first 16 weeks of treatment, with a high proportion achieving pasi 75, pasi 90, dlqi 0/1, and pga 0/1 responses, which were durable to week 128 of treatment. objectives to assess the long-term efficacy of czp dosed at 400 mg every two weeks (q2w), in addition to the durability of response in patients who achieve pasi 75 after an initial 16 weeks of treatment. background • plaque psoriasis (pso) is an immune-mediated, inflammatory disease that affects around 2−4% of the population in western countries.1 • certolizumab pegol (czp) is a unique fc-free, pegylated, anti-tumor necrosis factor approved by the fda and ema for the treatment of moderate to severe pso.2,3 • in phase 3 trials, patients with moderate to severe pso have demonstrated a durable response to czp over one year (48 weeks) of double-blinded treatment.4,5 • here, we report the long-term clinical responses for patients with pso who received open-label treatment with czp dosed at 400 mg every two weeks (q2w) for up to 128 weeks. methods study design • data were pooled from three phase 3 trials in adults with pso: cimpasi-1 (nct02326298), cimpasi-2 (nct02326272), and cimpact (nct02346240). full study designs have been reported previously.4,5 • at week 0, patients were randomized to receive czp 200 mg q2w (400 mg loading dose at weeks 0/2/4), czp 400 mg q2w, etanercept (cimpact only), or placebo. • patients included in this analysis: – were randomized to placebo at week 0 – failed to achieve a 50% improvement from baseline in psoriasis area and severity index (pasi 50) at week 16 – entered the open-label escape arm where they received czp 400 mg q2w for up to 128 weeks (figure 1) • dosing adjustment was permitted from week 48 of the study based on pasi response and the investigator’s discretion. • patients who did not achieve pasi 50 at any visit after receiving unblinded czp 400 mg q2w for 16 weeks were withdrawn from the study. patients • patient inclusion and exclusion criteria have been reported previously.4,5 k. gordon,1 r.b. warren,2 a.b. gottlieb,3 a. blauvelt,4 d. thaçi,5 y. poulin,6 m. boehnlein,7 f. brock,8 c. arendt,9 k. reich10 figure 1 study designs apresence of concurrent psa was self-reported. institutions: 1department of dermatology, medical college of wisconsin, milwaukee, wi, usa; 2dermatology centre, salford royal nhs foundation trust, manchester nihr biomedical research centre, the university of manchester, uk; 3department of dermatology, icahn school of medicine at mount sinai, new york, ny, usa; 4oregon medical research center, portland, or, usa; 5institute and comprehensive center for inflammation medicine, university of lübeck, lübeck, germany; 6centre de recherche dermatologique du québec métropolitain, québec, canada; 7ucb pharma, monheim am rhein, germany; 8ucb pharma, slough, uk; 9ucb pharma, brussels, belgium; 10centre for translational research in inflammatory skin diseases, institute for health services research in dermatology and nursing, university medical center hamburg-eppendorf and skinflammation® center, hamburg, germany. presented at fall clinical dermatology conference 2020 | october 29–november 1 | las vegas, nv durable efficacy of certolizumab pegol dosed at 400 mg every two weeks over 128 weeks in patients with plaque psoriasis enrolled in three phase 3 trials (cimpasi-1, cimpasi-2, and cimpact) references: 1parisi r. j invest dermatol 2013;133:377–85; 2certolizumab pegol prescribing information. available at http://www.accessdata.fda.gov; 3certolizumab pegol summary of product characteristics. available at http://www.ema.europa.eu/ema; 4gottlieb ab. jaad 2018;79:302–14; 5lebwohl m. jaad 2018;79:266–76. author contributions: substantial contributions to study conception/design, or acquisition/analysis/interpretation of data: kg, rbw, abg, ab, dt, yp, mb, fb, ca, kr; drafting of the publication, or revising it critically for important intellectual content: kg, rbw, abg, ab, dt, yp, mb, fb, ca, kr; final approval of the publication: kg, rbw, abg, ab, dt, yp, mb, fb, ca, kr. author disclosures: kg: honoraria and/or research support from abbvie, almirall, amgen, boehringer ingelheim, bristol-myers squibb, celgene, dermira inc., eli lilly, janssen, novartis, pfizer, sun pharma, and ucb pharma; rbw: research grants from abbvie, almirall, amgen, celgene, eli lilly, janssen, leo pharma, novartis, pfizer and ucb pharma; consultant for abbvie, almirall, amgen, arena, avillion, bristol myers squibb, boehringer ingelheim, celgene, eli lilly, janssen, leo pharma, novartis, pfizer, sanofi and ucb pharma; abg: current consulting/advisory board agreements with abbvie, avotres therapeutics, beiersdorf, boehringer ingelheim, bristol-myers squibb, celgene, eli lilly, incyte, janssen, leo pharma, novartis, sun pharma, ucb pharma, and xbiotech; research and educational grants from boehringer ingelheim, incyte, janssen, novartis, ucb pharma, and xbiotech; ab: served as a scientific adviser and/or clinical study investigator for abbvie, aclaris, allergan, almirall, athenex, boehringer ingelheim, bristol-myers squibb, dermavant, dermira inc., eli lilly, forte, galderma, incyte, janssen, leo pharma, novartis, ortho, pfizer, rapt, regeneron, sandoz, sanofi genzyme, sun pharma, and ucb pharma, and as a paid speaker for abbvie; dt: honoraria for participation on advisory boards, as a speaker and for consultancy from abbvie, almirall, amgen, biogen-idec, boehringer ingelheim, bristol-myers squibb, celgene, ds-biopharma, eli lilly, galapagos, janssen, leo pharma, morphosis, novartis, pfizer, regeneron, samsung, sandoz-hexal, sanofi and ucb pharma; research grants received from celgene, leo pharma and novartis; yp: investigator (research grants) from abbvie, baxter, boehringer ingelheim, celgene, centocor/janssen, eli lilly, emd serono, gsk, leo pharma, medimmune, merck, novartis, pfizer, regeneron, takeda, and ucb pharma; speaker (honoraria) from abbvie, celgene, janssen, eli lilly, leo pharma, novartis, regeneron, and sanofi genzyme; mb, fb, ca: employees of ucb pharma; kr: served as advisor and/or paid speaker for and/or participated in clinical trials sponsored by abbvie, affibody, almirall, amgen, avillion, biogen, boehringer ingelheim, bristol myers squibb, celgene, centocor, covagen, dermira, eli lilly, forward pharma, fresenius medical care, galapagos, gsk, janssen, kyowa kirin, leo pharma, medac, msd, miltenyi biotec, novartis, ocean pharma, pfizer, regeneron, samsung bioepis, sanofi, sun pharma, takeda, ucb pharma, valeant/bausch health, and xenoport. acknowledgements: the studies were funded by dermira inc. in collaboration with ucb pharma. ucb pharma is the regulatory sponsor of certolizumab pegol in psoriasis. we thank the patients and their caregivers in addition to the investigators and their teams who contributed to this study. the authors acknowledge susanne wiegratz, msc, ucb pharma, monheim am rhein, germany for publication coordination and joe dixon, phd, costello medical, cambridge, uk, for medical writing and editorial assistance, and the costello medical design team for design support. all costs associated with development of this poster were funded by ucb pharma in accordance with the good publication practice (gpp3) guidelines. figure 2 response over 128 weeks of treatment with czp 400 mg q2w bsa: body surface area; bw: bi-weekly; czp: certolizumab pegol; dlqi 0/1: dermatology life quality index of 0 or 1, no effect of disease on quality of life; etn: etanercept; il: interleukin; mcmc: markov chain monte carlo; ld: loading dose; pasi: psoriasis area severity index; pasi 50/75/90: 50%/75%/90% improvement from baseline in pasi; pga 0/1: physician’s global assessment score of 0 or 1 (“clear” or “almost clear”) with ≥2-point improvement from baseline; psa: psoriatic arthritis; pso: plaque psoriasis; q2w: every two weeks; sd: standard deviation; tnf: tumor necrosis factor. open-label escape czp 400 mg q2w n=53 open-label escape czp 400 mg q2w, n=72 <pasi 50 – withdrawn (weeks 32–144) week 0 14412 16 4832 placebo q2w lda czp 400 mg q2w initial treatment period (double-blinded) maintenance period open-label period czp 200 mg q2w <pasi 50 czp 200 mg q2w possible dose adjustmentsb 1:2:2 randomization n=100 etn 50 mg bw czp 200 mg q2w czp 400 mg q2w <pasi 50 – withdrawn (weeks 32–144) placebo q2w lda initial treatment period (double-blinded) maintenance period open-label period washout <pasi 75 czp 200 mg q2w possible dose adjustmentsb 1:3:3:3 randomization n=57 week 0 14412 16 4832 aloading dose of czp 400 mg q2w at weeks 0, 2, and 4; bdepending on pasi response, any dose adjustments were either mandatory or at the investigator’s discretion. only relevant treatment arms shown. figure 3 maintenance of response in patients who achieved pasi 75 following 16 weeks of treatment with czp 400 mg q2w pasi 75 pga 0/1 pasi 90 dlqi 0/1 c z p 4 0 0 m g q 2 w c z p 4 0 0 m g q 2 w p la c e b o p la c e b o p la c e b o r e sp o n d e r ra te in a ll p a ti e n ts ( % ) week 12811296806448320 14416 r e sp o n d e r ra te in p a s i 7 5 re sp o n d e rs ( % ) week 12811296806448320 14416 r e sp o n d e r ra te in a ll p a ti e n ts ( % ) week 12811296806448320 14416 r e sp o n d e r ra te in p a s i 7 5 re sp o n d e rs ( % ) 80 60 40 20 100 0 week 12811296806448320 14416 p la c e b o open-label period: 66.0% who entered this period remained on czp 400 mg q2wa,b open-label period: 66.0% who entered this period remained on czp 400 mg q2wa,b open-label perioda open-label perioda 68.0% 61.0%59.2% 50.2% 82.4% 71.8% 64.4% 100.0% 81.7% 65.9% 74.7% 65.4% 48.7% 75.5% 66.4% 57.6% 80 60 40 20 100 0 80 60 40 20 100 0 80 60 40 20 100 0 patients who were mandatorily withdrawn from week 32 onwards were treated as non-responders at subsequent timepoints. other missing data were imputed using mcmc methodology and responder rates reflect the simple average response and include patients who did and did not dose adjust during the open-label period. adepending on pasi response, dose reductions to czp 200 mg q2w were permitted at the discretion of the investigator; b64 of the 97 patients (66.0%) who completed the trial to week 48 and continued into the open-label period remained on czp 400 mg q2w for the remainder of the trial. table 1 demographics and baseline characteristics of included patients placebo → czp 400 mg q2w (n=116) age (years), mean ± sd 46.4 ± 12.6 male, n (%) 76 (65.5) caucasian, n (%) 108 (93.1) weight (kg), mean ± sd 94.0 ± 26.1 duration of pso (years), mean ± sd 17.7 ± 12.1 concomitant psa,a n (%) 19 (16.4) pasi, mean ± sd 18.8 ± 6.7 bsa (%), mean ± sd 23.2 ± 13.9 pga score, n (%) 3: moderate 81 (69.8) 4: severe 35 (30.2) dlqi total score, mean ± sd 12.9 ± 7.4 any prior systemic therapy use for pso, n (%) 87 (75.0) prior biologic use, n (%) 33 (28.4) anti-tnf 19 (16.4) anti-il-17 12 (10.3) anti-il-12/il-23 6 (5.2) previously presented at aad 2020 a) cimpasi-1 and cimpasi-2 b) cimpact a) pasi 75, pasi 90, and pga 0/1 response (n=116) a) pasi 75, pasi 90, and pga 0/1 response (n=82) b) dlqi 0/1 response (n=116) b) dlqi 0/1 response (n=82) skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 854 in-depth review apremilast in the management of generalized granuloma annulare: a case series jazmine nesvik, do1, leslie marshall, do2, david cleaver, do3, jonathan cleaver, do3, lloyd cleaver, do3 1 northeast regional medical center, kirksville, mo 2 ozarks medical center, west plains, mo 3 cleaver dermatology, kirksville, mo granuloma annulare (ga) is a benign cutaneous disease that appears as erythematous papules coalescing into annular plaques with granulomatous inflammation seen histologically.1 the most common clinical phenotypes include localized ga, subcutaneous ga, and generalized ga (gga). although ga is commonly self-limited, gga is diffuse and tends to be the subtype most refractory to treatment with the possibility of persisting for years.2 commonly employed treatment modalities have not been thoroughly studied outside of case studies or series. however, there is strong expert consensus for intralesional triamcinolone as first-line therapy. other treatment modalities that have shown some efficacy in ga include puva, uva1, narrowband uvb, pulsed-dye laser, abstract background: granuloma annulare is a difficult disease to treat and can lead to anxiety and frustration for both patients and providers. the pathogenesis of granuloma annulare is unknown, resulting in few thoroughly studied or consistently effective treatments. objective: 1) to discuss whether treatment with apremilast could lead to improvement or resolution of generalized granuloma annulare. 2) to explore the possible pathogenesis of granuloma annulare and the mechanism of apremilast in treating this disease. methods: a case series was used to study the clinical response of 6 patients with a history of recalcitrant generalized granuloma annulare taking apremilast 30mg twice daily. results: two patients achieved complete clearance of their disease without recurrence while the remaining 4 patients achieved significant improvement in lesion number, induration, and erythema. limitations: this is a small case series and larger, controlled trials with long-term follow-up are needed. there is no objective method for evaluating the extent of disease improvement in granuloma annulare. furthermore, our patients used concomitant topical and intralesional steroids while on apremilast. conclusion: this case series illustrates a novel therapy, apremilast, a phosphodiesterase-4 inhibitor, in the treatment of patients with generalized granuloma annulare and explores possible mechanisms behind the success of this treatment. introduction skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 855 antimalarial drugs such as chloroquine and hydroxychloroquine, tnf-alpha inhibitors, fumaric acid esters, and vitamin e, among others.1 ga has been associated with several diseases including diabetes, hyperlipidemia, hypothyroidism, systemic lupus erythematosus, rheumatoid arthritis, and hypertension.3 hypertension, however, may not be independently associated with ga and instead secondarily associated via its association with hyperlipidemia and diabetes. the etiology of ga is unknown; however, several theories have been proposed. multiple studies support the hypothesis of ga being triggered by a delayed-type iv hypersensitivity.4 low levels of tgf-beta and elevations in il-1 and il-2 receptors were identified in one study, leading authors to conclude that collagen synthesis is regulated by helper t cells as a result of a reparative mechanism in ga.4 an additional theory is that ga represents an immune-mediated, type iii hypersensitivity reaction resulting in a chronic vasculitis.5 apremilast is an oral, small molecule that inhibits phosphodiesterase-4 (pde4).6 phosphodiesterases typically degrade camp intracellularly. apremilast’s inhibition of pde4 prevents camp from being degraded leading to increased levels of camp, a second messenger important in regulating inflammation in numerous cell types throughout the body. side effects from apremilast are very mild and most commonly include diarrhea, nausea, headache, upper respiratory tract infection, and nasopharyngitis.7 after exhausting standard treatment options for patient 1’s gga without success, she expressed frustration and embarrassment over her extensive ga lesions. needing to explore other off-label options for this patient, it was decided to trial apremilast given its known anti-inflammatory effects and wellstudied safety profile with minimal adverse effects. once success was seen with treating this first patient, we continued to trial apremilast in additional patients experiencing recalcitrant gga which we discuss in this case series. we report six cases of recalcitrant gga in five females and one male who experienced improvement in their disease while on apremilast. the time from diagnosis to apremilast initiation ranged from 3 months to 5 years (table 1). the patients had a variety of associated comorbidities, including obesity, diabetes, and hypothyroidism. the diagnosis of ga was made clinically in all 6 patients and was further confirmed with punch biopsy in 4 of the 6 patients. all 6 failed multiple treatments for ga including topical, intralesional, and oral steroids; narrowband uvb; hydroxychloroquine; and minocycline. given the patients continued pruritus and cosmetic concerns over the lesions, further treatment was desired. each patient was initiated on an apremilast starter pack, beginning with 10mg daily on day 1 and titrating up to 30mg twice daily by day 7. patient responses were assessed by physicians during in-person clinic visits every 1-3 months based upon improvement in number, size, and appearance of lesions including induration and erythema. all patients experienced improvement of their gga as early as 4 weeks after initiation. responses varied, ranging from complete clearance without relapses to significant improvement in lesion induration, erythema, and number. a summary of patient responses is shown in table 1. duration of control on apremilast ranged from 6 months case report skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 856 table 1. individual patient characteristics, response to treatment, and treatment status. patient 1 patient 2 patient 3 patient 4 patient 5 patient 6 age (years) 30 66 61 73 45 67 sex f f f f m f comorbidities obesity, htm obesity, sebopso obesity, diabetes obesity, hld, hx breast ca hld, htm diabetes, hld, hx uterine ca morphology generalized pink papules coalescing into large plaques generalized pink annular papules and plaques generalized pink papules and plaques annular pink papules on arms, neck annular pink papules on upper and lower extremities generalized pink to orange papules coalescing into large plaques time to response on apremilast 3 months 6 weeks 4 weeks unknown 3 months 10 weeks duration of control on apremilast 47 months 20 months 8 months 10 months 6 months 6 months response to apremilast mostly clear with rare mild flares complete clearance after 6 weeks without relapse significant improvement in induration and plaque number significant improvement in lesion induration, erythema, and number complete clearance without relapse significant improvement in lesion induration, erythema, and number reason for discontinuing n/a – still on 30 mg qd n/a – still on 30 mg bid stopped responding after temporarily discontinuing stopped responding after temporarily discontinuing n/a – still on 30 mg bid ran out of medication biopsy confirmed yes no yes yes yes no adverse effects none none none none none none previously failed treatments topical, oral, and il steroids topical steroids topical steroids, hcq hcq, minocycline, oral steroids topical and il steroids, minocycline topical and il steroids concomitant therapies topical steroids topical steroids topical steroids topical and il steroids il steroids topical steroids skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 857 figure 1. patient 1 treatment response. figure 2. patient 2 treatment response. figure 3. patient 5 treatment response. skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 858 to 47 months and counting. three patients who are either mostly clear or completely clear still remain on apremilast. patient 1 has been well-controlled on 30mg daily for 47 months (figure 1). an attempt was recently made to decrease to 30 mg daily instead of twice daily apremilast, but this triggered a flare which resolved when she resumed 30mg twice daily. patients 2 and 5 are completely clear on 30mg twice daily (figures 2 and 3). patients 3 and 4 stopped responding after temporary apremilast discontinuation unrelated to medication adverse effects and did not respond when apremilast was reinitiated. patient 6 selfdiscontinued after running out of medication although she was improving while taking it. none of the patients experienced any medication-related adverse events. as mentioned above, apremilast is a pde4 inhibitor that leads to increased camp within cells. in diseases with increased expression of pde4 isoforms, such as psoriasis, decreased intracellular camp results in elevated levels of pro-inflammatory mediators and decreased levels of antiinflammatory mediators.6 by inhibiting pde4 in psoriasis, apremilast leads to increased camp and decreased pro-inflammatory mediators, including tnf-alpha, ifn-gamma, and il-2. notably, increased il-2 production has also been identified in ga lesions.8 in our patients’ cases, we theorize apremilast works mechanistically for ga similarly to how it works for psoriasis. given that il-2 production and increased il-2 receptors have been identified in ga, apremilast may interfere with il-2 production in t cells. alternatively, it could interfere with macrophage activation via ifn-gamma receptors on t-cells or tissue destruction by macrophages via tnf-alpha, all through suppression by camp. furthermore, apremilast may function on a broader level in ga by interfering with the release of proinflammatory cytokines or by increasing the release of anti-inflammatory cytokines via camp. we also must consider the possibility that the patients’ gga resolved as part of its natural course in conjunction with the administration of apremilast, although this is unlikely to have happened in all 6 patients shortly after medication initiation after years of recalcitrant disease. another limitation of our study is the fact that the study type is a case series. a larger, randomized controlled trial would be beneficial to determine if apremilast is effective for gga. additionally, most of our patients were concomitantly treated with intralesional and topical steroids while on apremilast which could have influenced their disease course. further, a more objective evaluation of disease improvement would be beneficial. other case studies on this subject mentioned that biopsying the lesions could be a limitation to the study as it may stimulate resolution of the disease. however, only 4 out of 6 of our patients had confirmation biopsies, which makes it less likely that the patients’ disease resolved secondary to biopsy trauma. at the time of writing, four case studies with a cumulative total of 9 patients have been published on the treatment of gga with apremilast. our case series adds 6 patients to this total further supporting the use of apremilast as a novel treatment for gga. it also follows patients over a longer period comparatively. our study is also differentiated from the four patient case series by blum and altman in that our patients continued topical and intralesional steroids during treatment with apremilast while their patients discontinued steroid use.9 discussion skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 859 this case series illustrates a novel therapy, apremilast, in the successful treatment of six patients with recalcitrant gga. pde4 inhibition in ga may exert its effect by decreasing pro-inflammatory cytokines, decreasing il-2 production, increasing ifngamma stimulation or tnf-alpha release, or increasing anti-inflammatory cytokines, likely through a second messenger pathway involving increased camp. our study further supports prior literature regarding the use of apremilast as a novel treatment for recalcitrant gga. larger, controlled trials with long-term follow-up are needed to further evaluate the efficacy of apremilast in the treatment of gga. ga = granuloma annulare, gga = generalized granuloma annulare, puva = psoralen plus ultraviolet a phototherapy, uva1 = ultraviolet a1 phototherapy, uvb = ultraviolet b phototherapy, m = male, f = female, n/a = not applicable, qd = daily, bid = twice daily; hld = hyperlipidemia; hcq = hydroxychloroquine; htm = hypothyroidism; ca = cancer; sebopso = sebopsoriasis; il = intralesional; hx = history conflict of interest disclosures: none funding: none corresponding author: jazmine nesvik, do 315 s osteopathy kirksville, mo 63501 email: jazminenesvik@atsu.edu phone: (320) 491-0988 references: 1. piette, e., and m. rosenbach. “granuloma annulare.” journal of the american academy of dermatology, vol. 75, no. 3, 1 sept. 2016, pp. 457–465. 2. lukács, j., et al. “treatment of generalized granuloma annulare a systematic review.” journal of the european academy of dermatology and venereology, vol. 29, no. 8, 2015, pp. 1467–1480., doi:10.1111/jdv.12976. 3. barbieri, john s., et al. “association of granuloma annulare with type 2 diabetes, hyperlipidemia, autoimmune disorders, and hematologic malignant neoplasms.” jama dermatology, vol. 157, no. 7, 1 july 2021, doi:10.1001/jamadermatol.2021.1805. 4. kallioinen m, sandberg m, kinnunen t, oikarinen a. collagen synthesis in granuloma annulare. journal of investigative dermatology. 1992;98:463–8. 5. dahl mv, ullman s, goltz rw. vasculitis in granuloma annulare: histopathology and direct immunofluorescence. arch of dermaol. 1977;113:463–7. 6. schafer p. apremilast mechanism of action and application to psoriasis and psoriatic arthritis. biochem pharm. [internet]. 2012;83:1583–90., doi:10.1016/j.bcp.2012.01.001. 7. p.j. mease, a. kavanaugh, d.d. gladman, et al. “2013 annual meeting abstract supplement.” arthritis & rheumatism, vol. 65, no. s10, 2013, doi:10.1002/art.38216. 8. mempel m, musette p, flageul b, schnopp c, remling r, gachelin g, et al. t-cell receptor repertoire and cytokine pattern in granuloma annulare: defining a particular type of cutaneous granulomatous inflammation. j invest dermatol. 2002;118:957–66. 9. blum, stacy, and david altman. “treatment of generalized granuloma annulare with apremilast: a report of 2 cases.” jaad case reports, vol. 5, no. 11, 11 nov. 2019, pp. 976–978., doi:10.1016/j.jdcr.2019.09.015. 10. bishnoi, anuradha, et al. “refractory generalized granuloma annulare treated with oral apremilast.” jama dermatology, vol. 155, no. 11, 21 aug. 2019, p. 1318., doi:10.1001/jamadermatol.2019.2130. 11. hansel, k., et al. “generalized granuloma annulare successfully treated with apremilast: report of two cases and literature review.” clinical and experimental dermatology, 29 june 2021, doi:doi.org/10.1111/ced.14806. 12. tejas, joshi p., and jaime tschen. “apremilast in the management of disseminated granuloma annulare.” cureus, 9 may 2021, doi:10.7759/cureus.14918. conclusion poster presented at the winter clinical dermatology conference, january 12–17, 2018, lahaina, hi, usa introduction • chronic idiopathic/spontaneous urticaria (ciu/csu) is defined as the repeated occurrence of spontaneous wheals (hives) and/or angioedema for at least 6 weeks without a specific external trigger1,2 • between 33% and 67% of patients with ciu/csu are reported to experience hives and angioedema; 1%–13% experience only angioedema3 • angioedema is a major driver of quality of life (qol) impairment in patients with ciu/csu;4 owing to the unpredictable development of disfigurement and/or functional impairment, angioedema episodes can have a significant impact on daily activities and social interactions5 • omalizumab is approved as an add-on therapy in patients with ciu/csu refractory to h1-antihistamines.6 subcutaneous omalizumab (300 mg) has been shown to reduce the frequency and severity of angioedema in h1-antihistamine-refractory ciu/csu, as well as reducing qol impairment7 omalizumab improves angioedema-related quality of life (qol) impairment in patients with chronic idiopathic/chronic spontaneous urticaria (ciu/csu): results from the x-act study karsten weller,1 petra staubach,2 martin metz,1 nadine chapman-rothe,3 christian sieder,4 matthias bräutigam,4 marcus maurer1 1charité – universitätsmedizin berlin, berlin, germany; 2university medical center mainz, mainz, germany; 3novartis pharma ag, basel, switzerland; 4novartis pharma gmbh, nuremberg, germany patient-reported outcomes: qol, disease activity, and psychological well-being • outcomes reported in this poster were measured using the following assessments: – ae-qol: angioedema quality of life questionnaire; 17 items that include four subdomains (functioning, fatigue/mood, fears/shame, and food). scores range from 0 to 100, with higher scores indicative of higher impairment to qol – weekly aas (aas7): angioedema activity score; scores range from 0 to 105, with higher scores indicating higher disease activity – who-5: world health organization well-being index; a 5-item questionnaire with a maximum score of 25. values lower than 13 indicate signs of depression statistical analysis • in the full analysis set (fas; all those randomized who received ≥1 dose of study drug), patients were analyzed according to the treatment to which they were randomized • treatment group comparisons of change in ae-qol scores were performed using an analysis of covariance (ancova) model with treatment and center as factors, and baseline score as a covariate. the analysis was conducted in the fas by using observed values for ae-qol scores5 • the aas7 and who-5 results were analyzed analogously to the ae-qol as a mean difference from baseline to week 28 in an ancova conducted on the fas by using observed cases5 • the who-5 assessment and the question regarding fear of a life-threatening swelling episode were regarded as exploratory endpoints • pearson correlation coefficients were computed to explore the correlations between different endpoints5 results patients • a total of 91 patients were randomized, with 68 (omalizumab, n=35; placebo, n=33) completing the 28-week treatment period • patient demographics and baseline disease characteristics are shown in table 1 – female patients had higher ae-qol total scores at baseline compared with male patients (p=0.001) and a tendency toward higher disease activity (higher aas7 scores, p=0.086) conclusions • omalizumab 300 mg treatment led to a rapid and sustained reduction of angioedema-related qol impairment − this is correlated with decreased angioedema activity • omalizumab rapidly improved ae-qol subdomain scores for functioning, fatigue/mood, and fear/shame − numerical improvements in the food subdomain were observed but did not reach statistical significance • discontinuation of omalizumab treatment resulted in the return of angioedema symptoms • symptom-related fears of suffocation and life-threatening episodes in the omalizumab group decreased versus those in the placebo group, supporting the benefit of omalizumab treatment in patients with ciu/csu with h1-antihistamine-refractory angioedema and decreased qol • general psychological well-being improved with omalizumab treatment, as indicated by increased mean who-5 scores to levels above the depression threshold table 2. patient fear of a life-threatening swelling episode (baseline to follow-up at week 36) baseline week 4 week 12 week 28 follow-up omalizumab (n=44) placebo (n=46) omalizumab (n=43) placebo (n=45) omalizumab (n=37) placebo (n=34) omalizumab (n=22) placebo (n=24) omalizumab (n=32) placebo (n=28) 'were you afraid of a life-threatening swelling episode?' never 7 (15.9) 6 (13.0) 19 (44.2) 15 (33.3) 20 (54.1) 11 (32.4) 14 (63.6) 7 (29.2) 12 (37.5) 10 (35.7) rarely 11 (25.0) 6 (13.0) 11 (25.3) 7 (15.6) 6 (16.2) 9 (26.5) 5 (22.7) 7 (29.2) 10 (31.3) 4 (14.3) occasionally 11 (25.0) 16 (34.8) 3 (7.0) 16 (35.6) 9 (24.3) 6 (17.6) 3 (13.6) 7 (29.2) 6 (18.8) 10 (35.7) often 8 (18.2) 11 (23.9) 7 (16.3) 6 (13.3) 1 (2.7) 3 (8.8) 0 (0.0) 1 (4.2) 3 (9.4) 2 (7.1) very often 7 (15.9) 7 (15.2) 3 (7.0) 1 (2.2) 1 (2.7) 5 (14.7) 0 (0.0) 2 (8.3) 1 (3.1) 2 (7.1) data presented as n (%). table 1. patient demographics and baseline disease characteristics omalizumab (n=44) placebo (n=47) age, years, mean (sd) 44.9 (13.7) 41.1 (10.6) female, n (%) 30 (68.2) 33 (70.2) bmi, mean (sd) kg/m2 27.3 (6.3) 29.0 (5.9) aas7, mean (sd) 22.5 (20.6) 28.1 (24.1) angioedema-burdened days, mean (sd)a 2.7 (2.3) 3.5 (2.4) ae-qol total score, mean (sd) 56.2 (18.7) 59.9 (19.2) dlqi total score, mean (sd) 14.6 (5.7) 16.6 (7.3) aat week 1 during the 2-week screening period. aas7, weekly angioedema activity score; ae-qol, angioedema quality of life questionnaire; bmi, body mass index; dlqi, dermatology life quality index; sd, standard deviation. objective • to examine the effect of omalizumab treatment on angioedema-related qol, including patient fear of a life-threatening angioedema (swelling) episode, in the x-act study (nct01723072) methods study design • the x-act (xolair effects on angioedema in chronic spontaneous urticaria treatment) study was a phase 3, randomized, double-blind, placebo-controlled, multicenter study conducted in germany7 • patients were randomized 1:1 to receive subcutaneous omalizumab 300 mg or placebo every 4 weeks for 28 weeks, with an 8-week follow-up period (figure 1) angioedema-related qol and disease activity • improvement in angioedema-related qol correlated with reduced angioedema activity (week 12: 0.526, p<0.001; week 28: 0.501, p<0.001; pearson correlation coefficient) • after treatment discontinuation, both angioedema-related qol impairment and angioedema activity approached placebo levels (figure 2) – least squares (ls) mean difference (95% confidence interval [ci]) in ae-qol score for omalizumab versus placebo at: week 4, −17.6 (−26.9, −8.2); week 12, −26.0 (−38.1, −13.9); week 20, −16.3 (−27.6, −5.0); week 28, −22.7 (−33.1, −12.2) – ls mean difference (95% ci) in aas7 for omalizumab versus placebo at: week 4, −15.6 (−22.7, −8.6); week 12, −14.1 (−22.7, −5.5); week 20, −7.0 (−14.1, 0.2); week 28, −9.8 (−18.9, −0.7) scan this qr code visit the web at: http://novartis.medicalcongressposters.com/default.aspx?doc=f0252 mobile friendly e-prints 3 ways to instantly download an electronic copy of this poster to your mobile device or e-mail a copy to your computer or tablet text message (sms) text: qf0252 to: 8nova (86682) us only +18324604729 north, central and south americas; caribbean; china +447860024038 uk, europe & russia +46737494608 sweden, europe standard data or message rates may apply. days −14–1 (2 weeks) randomization days 1–197 (28 weeks) days 198–253 (8 weeks) omalizumab 300 mg s.c. every 4 weeks placebo s.c. every 4 weeks screening period follow-up perioddouble-blind treatment period ae-qol evaluationmonthly omalizumab or placebo treatment primary efficacy endpoint figure 1. x-act study design ae-qol, angioedema quality of life questionnaire; s.c., subcutaneous. functioning c h a n g e f ro m b a s e li n e , m e a n ( s d ) 0 −10 −20 −30 −40 −50 −60 −70 fatigue/mood fear/shame food *** ** * omalizumab placebo figure 3. change from baseline in ae-qol subdomain scores at week 4 change versus placebo: *p<0.05; **p<0.01; ***p<0.001. ae-qol, angioedema quality of life questionnaire; sd, standard deviation. 15.0 10.8 16.7 12.1 18.6 11.5 15.2 11.6 baseline 10.0 7.7 m e a n ( s d ) to ta l s c o re 25 20 15 10 5 0 week 4 week 12 week 28 follow-up depression threshold (who-5 index total score: 13) * *** *** omalizumab placebo figure 4. who-5 index total scores omalizumab versus placebo: *p<0.05; ***p<0.001. sd, standard deviation; who-5, 5-item world health organization well-being index. baseline m e a n ( s d ) s c o re 70 60 50 40 30 20 10 0 4 *** *** *** ** 12 20 28 follow-up weeks ae-qol total score omalizumab placebo baseline m e a n ( s d ) s c o re 35 30 25 20 15 10 5 0 4 *** ** *p=0.056 12 20 28 follow-up weeks aas7 figure 2. angioedema-related qol and disease activity omalizumab versus placebo: *p<0.05; **p<0.01; ***p<0.001. aas7, weekly angioedema activity score; ae-qol, angioedema quality of life questionnaire; sd, standard deviation. • as early as week 4, patients in the omalizumab group had significantly greater improvements from baseline in three subdomains of the ae-qol compared with the placebo group (figure 3) fear of life-threatening swelling episode • at baseline, when patients were asked if they were afraid of a life-threatening swelling episode, 67% responded ‘occasionally’, ‘often’, or ‘very often’. at week 28, this decreased to 13.6% in the omalizumab group versus 41.7% in the placebo group • similarly, 49% of patients at baseline were ‘occasionally’ to ‘very often’ afraid that ‘they could suffocate due to swelling episode’. at week 28, this decreased to 4.5% in the omalizumab group versus 25.1% in the placebo group • reduced fear of life-threatening swelling episodes was evident from as early as 4 weeks after starting omalizumab treatment, but increased upon discontinuation of treatment psychological well-being • omalizumab treatment, but not placebo, increased the mean who-5 total score to levels above the depression threshold (indicating no signal for depression) (figure 4) study population • key inclusion criteria for the x-act study included: – age 18–75 years – moderate-to-severe ciu/csu with frequent angioedema episodes (≥4 episodes within the last 6 months before study enrollment) – medically confirmed diagnosis of ciu/csu that is refractory to treatment with 2–4 times the approved dose of second-generation h1-antihistamines – at week 28, 63.6% of patients in the omalizumab group were ‘never’ afraid of life-threatening swelling episodes compared with 29.2% in the placebo group. during the follow-up period, these proportions were 37.5% and 35.7% in the omalizumab and placebo groups, respectively (table 2) acknowledgments medical writing in the development of this presentation was provided by novartis ireland ltd. editorial assistance was provided by heather st michael of fishawack communications ltd, abingdon, uk, and this service was supported by novartis pharmaceuticals corporation, east hanover, nj, usa. the scientific content of this poster was originally presented orally at the 36th annual congress of the european academy of allergy and clinical immunology, june 17–21, 2017, helsinki, finland. funding this study was supported by novartis pharma gmbh, germany. disclosures in relation to this presentation, we declare the following real or perceived conflicts of interest: kw has received honoraria for educational lectures (dr r. pfleger, essex pharma [now msd], moxie, novartis, ucb, uriach); has received honoraria for consulting (novartis); was involved in clinical research projects (dr r. pfleger, essex pharma [now msd], faes, novartis, uriach). ps has received research funding and/or fees for consulting and/or lectures (abbvie, astellas, celgene, csl behring, dr r. pfleger [now msd], genentech, janssen, karrer, leo, leti, lilly, msd, novartis, pfizer, shire, sobi, ucb). mmetz has received honoraria as a speaker (bayer pharma, dr r. pfleger [now msd], essex pharma, leo, merck, moxie, novartis, recordati pharma, sanofi, shire, ucb, uriach). nc-r is an employee of novartis pharma ag. cs and mb are employees of the study sponsor, novartis pharma gmbh. mmau has received research funding and/or fees for consulting and/or lectures (faes, genentech, gsk, moxie, msd, novartis, ucb, uriach). references 1. zuberbier t, et al. allergy. 2014;69:868–87. 2. grattan c. clin med. 2012;12:164–7. 3. maurer m, et al. allergy. 2011;66:317–30. 4. choi ws, et al. korean j intern med. epub ahead of print jun 1, 2016. doi: 10.3904/ kjim.2015.195. 5. staubach p, et al. allergy. epub ahead of print oct 23, 2017. doi: 10.1111/all.13339. 6. mccormack pl. drugs. 2014;74:1693–9. 7. staubach p, et al. allergy. 2016;71:1135–44. skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 407 research letter topical corticosteroid clinical decision support for primary care providers: there’s an app for that! laura burbach1, melissa butt, mph 2, jessica butts, md3, todd felix, md3, daniel schlegel, md3, kassidy shumaker2, joslyn s kirby, md, ms, med2 1penn state college of medicine, hershey pa 2department of dermatology, penn state milton s. hershey medical center, hershey pa, 3department of family and community medicine, penn state milton s. hershey medical center, hershey, pa literature has indicated that 20-36% of patients in pcp offices have dermatologic conditions1. pcps have been shown to prescribe inappropriately high-potency topical corticosteroids (tcs), or, conversely, inappropriately low-potency tcs.2 in addition, drug costs may be higher if multiple small tubes are dispensed over the treatment course.3 importantly, mobile devices and applications provide significantly increased access to point-of-care tools and, with use by providers, demonstrate better clinical decision-making and improved patient outcomes.4,5 the focus of this study was to develop and evaluate an application (‘app’) designed as a clinical decision support for pcp use of tcs. the app was developed using clinical practice guidelines for topical corticosteroid use. app design and functionality was iteratively developed by a multidisciplinary group of professional app designers (3), pcps (3), and dermatology providers (3). a study of the app was performed with pcps to determine changes in potency, vehicles and amount of corticosteroid prescriptions before and after app use (corticocream calculator, https://www.padermatology.org/corticreamcalculator.html). the study was approved by the penn state institutional review board. pcps were recruited on june 7, 2017, then 3 months later their prescription records were retrieved for the three months before and after the recruitment date (march 7september 7, 2017). surveys collected participants’ perceptions of app utility, performance, and pcps’ perceptions about their personal confidence in prescribing tcs. descriptive statistics were performed and the t test, chi-square test or fisher’s exact test were used to determine statistical significance. study sample characteristics are reported in table 1. there was an increase in the percentage of prescriptions for intermediate sized (45-170g) units, with a baseline percentage of 48.6% and an increase to 58.6%. there was a decrease in the percentage of prescriptions for small sized (15-30g) units, with a baseline percentage of 42.0% and a decrease to 36.3% (p=.07). there was also a shift away from low-potency towards high-potency tcs (figure 1). lowpotency prescriptions decreased from 25% to 22.6% and high-potency increased from 16.0% to 19.0% after initiating app use, but weren’t statistically significant (p=.68). there skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 408 were shifts in the choice of vehicles, with an increase from 4.7% to 7.1% for shampoo, gel, solution and foam, which are sometimes preferred for hair-bearing areas (p=.55). survey results, collected at 0, 1, and 3 months of application use, showed an increase in certainty of prescribing appropriate quantity and vehicle. certainty for quantity increased from 30.8% to 46.1% (p=.27). similarly, certainty for vehicle increased from 30.8% to 61.5% (p=.29). lastly, the application was described as “very easy to use,” “intuitive” and “an excellent tool,” with one participant commenting it “broadened [their] knowledge of what to use and how much to give.” in conclusion, a clinical decision app increased pcps’ perception of certainty when prescribing steroids and resulted in nearly significant differences in amounts of tcs prescribed to patients. there were figure 1: potency, vehicle and volume prescription habits before and after use of application. skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 409 changes, though not statistically significant in higher potency steroids and more vehicle diversity associated with app use. this app could aid pcps in their management of patients and reduce unnecessary appointments to dermatologists. this would offer dermatologists more availability for patients with urgent concerns or truly recalcitrant dermatoses. conflict of interest disclosures: none. funding: this study was supported in part by a research grant from pfizer independent grants for learning and change to the pennsylvania academy of dermatology and dermatologic surgery. pfizer had no responsibility for or input into the any analyses, interpretations, or conclusions. corresponding author: joslyn kirby, md, ms, med penn state hershey department of dermatology 500 university drive mail code hu14 hershey pa email: jkirby1@pennstatehealth.psu.edu references: 1. federman dg, concato j, kirsner rs. comparison of dermatologic diagnoses by primary care practitioners and dermatologists. a review of the literature. archives of family medicine. mar-apr 1999;8(2):170-172. 2. balkrishnan r, cook jm, shaffer mp, saltzberg fb, feldman sr, fleischer ab, jr. analysis of factors associated with prescription of a potentially inappropriate combination dermatological medication among us outpatient physicians. pharmacoepidemiology and drug safety. mar 2004;13(3):133-138. 3. skojec a, foulke g, kirby js. variation in the cost of generic topical corticosteroids. jama dermatology. aug 19 2015. 4. aungst td. medical applications for pharmacists using mobile devices. the annals of pharmacotherapy. jul-aug 2013;47(7-8):1088-1095. 5. ventola cl. mobile devices and apps for health care professionals: uses and benefits. p & t : a peer-reviewed journal for formulary management. may 2014;39(5):356-364. mailto:jkirby1@pennstatehealth.psu.edu skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 59 in-depth reviews caffeine in the treatment of atopic dermatitis and psoriasis: a review mais alashqar, md1, norman goldstein, md2 1alfaisal university, riyadh, saudi arabia 2department of dermatology, icahn school of medicine at mount sinai, new york, ny atopic dermatitis (ad) and psoriasis are inflammatory, t-cell mediated disorders of the skin. ad presents as erythematous, pruritic papules, exacerbated by xerosis. its chronic lesions become lichenified, hyperpigmented, and are often excoriated. [1] it usually starts in childhood, but may have an adult onset as well. [2] it was believed that the majority of children affected would outgrow this condition, but recent work in jama dermatology has shown that for most it will be a life-long disorder. [3] up to 20% of children in the world are affected by ad, and up to 3% of adults, so this disease is one of significant global burden. [4] psoriasis presents as well-demarcated micaceous plaques or papules, usually with silver scales. sometimes it presents with pustules, and many psoriasis patients also have nail and/or joint involvement. stress and infections usually worsen the symptoms. in a 2014 study, the prevalence of psoriasis in introduction atopic dermatitis (ad) and psoriasis are inflammatory skin diseases. ad is characterized by immune dysregulation and barrier impairment, while psoriasis is by immune dysfunction and resultant keratinocyte hyperproliferation. caffeine has shown positive effects on the symptoms of both diseases, but it is not conclusive through which pathways. the aim of this study was to provide a detailed discussion of available work on this topic, as well as known modes of action of caffeine that are relevant to these two conditions. after an extensive review of the literature, we found that both diseases have decreased intracellular cyclic adenosine monophosphate (camp) levels in cutaneous leukocytes, so it is very likely that being a methylxanthine, and hence a phosphodiesterase (pde) inhibitor, caffeine raises intracellular camp levels, which suppresses inflammatory pathways and potentiates anti-inflammatory ones. moreover, caffeine is known to be an atr (ataxia-telangiectasia mutated) kinase and an atm (atmand rad3-related) kinase inhibitor, which promotes prompt apoptosis of damaged cells. it was also found to have anti-necrotic effects in reactive oxygen species (ros)-damaged cells. these pro-apoptotic and anti-necrotic properties may also be reducing the inflammation. finally, caffeine's metabolites have shown antioxidizing effects against ros, which certainly would reduce inflammation caused by lipid peroxidation, dna damage and organelle destruction. we find that caffeine acts in a number of ways to improve symptoms of inflammation and that it may be an effective adjunct to therapy in ad and psoriasis. abstract skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 60 adults was reported as 3.2% in the united states.[5] topical caffeine has been shown to help both diseases, in a number of trials. below we review available work on the topic and currently known modes of action of caffeine in inflammatory skin disorders. these diseases are, at their core, idiopathic, but many theories exist to explain the laboratory and clinical findings associated with them. atopic dermatitis: atopic patients were known to have hypersensitivity to β-adrenergic blockade, which spiked an interest in the possible role of camp level abnormalities and βadrenergic dysregulation in ad. [6] there is a statistically significant decrease in camp levels of cutaneous and peripheral blood leukocytes in atopic dermatitis. [6] this decrease may be due to the increased activity of pde in these cells, as was reported in many studies. [7-11] normal pde levels in local and peripheral leukocytes have also been declared. [12, 24] despite the mixed results, pde inhibitors, which raise the intracellular camp, remain effective in the treatment of ad. [14-18] one such example is e6005. it is a topical, potent pde4 inhibitor that has proven to alleviate the pruritic component of ad, by multiple mechanisms: suppressing the proteinaseactivated receptor 2 (par2) effect (a known possible component of the pruritic pathway [19]) and by raising camp levels, which reduces ltb4 production in keratinocytes (also a possible component of the pruritic pathway [20]). [21-23] forskolin, also a camp elevator, has shown to have anti-pruritic properties. [22] rolipram, ro 20-1724, and nitraquazone have all been shown to improve ad as well, in a study from 1993. [24] in 2016, two double-blind studies confirmed the efficacy and safety of the use of crisaborole ointment, another pde4 inhibitor, in the treatment of ad. [14,25] higher camp levels have been shown to inhibit pro-inflammatory pathways, induce anti-inflammatory pathways, and affect gene expression (through modulation of camp response element-binding proteins (creb)) in leukocytes, keratinocytes, and cutaneous fibroblasts. [6,26] this includes reduced levels of ifnβ, ifn -γ, tnf-α, interleukin 12, inducible nitric oxide (no) synthase, leukotriene b4, macrophage inflammatory proteins 1α and 1β, and nuclear factorkappab; while increased production of interleukin 10. [6,26-28] theories that attempt to explain ad are many, but there is definitely a component of immune dysregulation and one of poor skin barrier function; yet which ignites the other remains controversial. [1] the outside-inside hypothesis suggests that genetic abnormalities cause a barrier dysfunction, and secondarily dermatitis. for example, flg gene mutations, affecting the filaggrin protein, impair the integrity of the corneal layer and tight junction mutations affect that of the granular layer of the skin in ad. [1] both of these mutations can increase the skin’s permeability to allergens, irritants, and infectious agents, that would ignite inflammation.[1] the inside-outside hypothesis, however, suggests the genetic abnormalities cause immune dysregulation first. ad leukocytes models of pathogenesis skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 61 have intrinsically higher levels of camp phosphodiesterase, and consequently lower intracellular camp and higher ige production, which suppresses the th1 immune responses, and promotes a th2-oriented response, with resultant cytokines and rosdamage weakening the barrier. [1] alternatively, the outside-inside-outside hypothesis suggests that the immune dysfunction and the impaired barrier act simultaneously to form a vicious cycle, both exacerbating one another. an impaired barrier would allow allergens to easily penetrate, and activate the inflammatory process, which being abnormal and exaggerated, would further damage the barricade. [1] regardless of the sequence, each component in the inflammatory pathway and the barrier dysfunction involved is a potential target for novel therapy. psoriasis: psoriasis is a multifactorial disease that remains largely idiopathic. it is known to be autoimmune and inflammatory, with both genetic and environmental triggers and aggravators. [1,29] in fact 71% of children affected have a family history of psoriasis, as reported by morris et al. [30] a vicious cycle exists in predisposed individuals, where an abnormal and inflated immune response to an allergen occurs, with cytokines released actually causing both inflammation, as well as keratinocyte hyperproliferation; hence the distinctive raised plaques and mica-like scales of psoriasis. [29] the cell cycle of the keratinocytes is also expedited. [31] these keratinocytes produce cytokines, themselves, that attract more leukocytes to the lesion, further propagating the cycle.[29] in psoriasis, as with ad, the findings include decreased camp levels. [32,33] some studies have countered this, and researchers offered that previously recorded camp levels were altered by the biopsying technique, or by the lack of β-adrenergic response and ischemic effect in psoriatic lesions. [34-36] the overwhelming mass of research, however, has recognized the beneficial effects of pde inhibitors for the treatment of psoriasis. the fact that they raise intracellular camp levels supports the initial notion that camp levels are decreased in leukocytes of psoriatic lesions. [19] for example, apremilast and benzoxaboroles (particularly crisaborole) are both pde4 inhibitors, and they have shown great results, diminishing psoriatic lesions and reducing inflammatory cytokine production. [6,38-40,44] caffeine has been shown to provide relief to ad patients. [45,46] in 1976, kaplan et al conducted a preliminary trial on 20 patients, where they compared the effectiveness of 10% caffeine (in a hydrophilic base) with a placebo, on the following scales: erythema, pruritus, scaling, oozing, lichenification, and overall subjective evaluation. [45] they found a statistically significant improvement in the overall subjective evaluation, so pursued a follow-up study using a caffeine concentration of 30% on 40 ad patients (28 were included in the analysis). [45,46] in the second research, published the year after, kaplan et al reported a statistically significant improvement in all scales tested in the caffeine group, while the placebo group showed improvement only in pruritus. [46] in pharmacology skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 62 1978, another study on 83 ad patients was published comparing three formulations (all in hydrophilic bases): 0.5% hydrocortisone ointment, caffeine 30% and hydrocortisone 0.5% ointment, and betamethasone valerate 0.1% cream. they noted improvement in all study groups on all scales; however, the caffeine-hydrocortisone group and the betamethasone group were significantly superior to the hydrocortisone group on the scales of excoriation, lichenification, and global impression. moreover, the caffeinehydrocortisone and the betamethasone groups did not differ statistically significantly on any scale. [47] the main side effect of the caffeine preparation was an immediate pruritic or burning sensation, which occurred in 4 out of an original 90 participants selected for the study. this may have been due to the “grittiness” of the caffeine blend, as described by the authors. [47] corticosteroids, on the other hand, may cause side effects such as pigment changes, perioral dermatitis, delayed wound healing, and others, making the use of caffeine to enhance the effect of lower concentrations of corticosteroids an attractive option. [47,48] in another trial, vali et al tested caffeine 10% (in a plastibase of liquid paraffin and polyethylene) on the plaque psoriasis of 39 patients, versus a placebo. a statistically significant difference was observed, but only after 8 weeks of treatment. one side effect was noted, which was mild pruritus. [49] caffeine as a pde inhibitor: caffeine is a methylxanthine, so is an inhibitor of the pde enzymes, and hence increases intracellular camp levels. as discussed earlier, this has an antiinflammatory effect, as it counteracts the noted decrease in camp levels in ad and psoriasis. in fact, kaplan et al and vali et al both associate their findings to this sequence. [45-47,49] caffeine as an atr kinase inhibitor: generally, when a cell in the body undergoes dna damage, checkpoint activations are induced and are followed by cell cycle arrest, and then apoptosis or dna repair. [50,51] the repair process, also known as the dna damage response (ddr), is a network of interlinked pathways, controlled by the atm (ataxia-telangiectasia mutated) and atr (atmand rad3-related) kinases. while atm is mainly concerned with doublestranded dna breaks (dsbs), atr is activated by many forms of dna damage, including dsbs.[50,52] the function of this process is to restore the dna; however, sometimes the repair is imperfect, and although allows the cell to survive, it causes abnormalities in the cell cycle, potentially leading to malignancy. [50,53] inhibition of these pathways induces unhazardous cell apoptosis instead. [63, 68] many studies have recognized the value of inhibiting atr and atm in 1) preventing cancers and 2) in improving therapeutic outcomes. work by charrier et al describes the use of aminopyrazines to inhibit atr, and so allow dna-damaging chemotherapy to work more effectively, by preventing the cancerous cells from repairing their dna after this tackle. [64] pires et al and fokas et al used the atr inhibitors ve-821 and ve822 to successfully improve outcomes of radiotherapy. [55,56] caffeine is also a known dna repair inhibitor, as described by lehmann and rauth. [52, 57] later work describes that gaps formed during dna replication in the daughter strands were skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 63 not repaired if caffeine was present in the medium. [57-60] in fact, caffeine has been used to enhance the cytotoxic effect of radio and chemotherapy in many trials. gaudin et al showed that caffeine could re-sensitize cytoxan-resistant plasmacytomas to the effects of x-rays, nitrogen mustard, and cytoxan. [61] rauth et al used it to enhance cytotoxicity to mitomycin c.[62] sarkaria et al identified caffeine as both an atr and an atm inhibitor and noted its ability to increase radiosensitivity of cultured cells. [63] zajdela et al conducted two independent experiments on healthy mice ears, where they coated one ear with 0.1% caffeine solution before irradiating both ears with uv light, to find that 89% of uncoated ears developed cutaneous tumors, while only 47%-54% of coated ears did. [64] upon rosinduced damage, caffeine was found to reduce necrosis of skin fibroblasts. [65] moreover, that study reported no statistically significant increase in the number of apoptotic fibroblasts, indicating that the antinecrotic effect may have been through another unidentified pathway. what is of interest to us here is that caffeine seems to possess both pro-apoptotic and anti-necrotic properties, which serve to inhibit inflammation caused by external factors. necrosis causes a sudden release of selfantigens and cell components into the surrounding milieu, which promotes harmful consequent inflammation.[66] at the same time, cells that are damaged beyond repair should be removed instantaneously by apoptosis. additionally, the inhibition of atr and atm has been shown to upregulate il10 gene expression, and il-10 is a prominent anti-inflammatory cytokine.[67] these properties may play a role in caffeine’s anti-inflammatory effect on psoriasis and ad. caffeine as an antioxidant: oxidants are chemical compounds with the ability to damage other particles by acquiring one or more of their electrons; thereby creating a self-propagating, destructive succession of free radicles. in the setting of a cell, such a sequence occurs commonly, from toxins or uv radiation for example, ionizing compounds. not only does this cause dna damage, but also inflammation by lipid peroxidation and other destructive processes. thankfully, antioxidants are abundant in the body, like glutathione. it is then a balance between the oxidants and the anti-oxidants. in 2007, a study reported that daily oral caffeine intake reduced the risk of nonmelanoma skin cancer by 30%.[68,69] later reports confirmed this relationship for melanoma as well. [70] an in vitro study by chu et al found that crude caffeine had antioxidant activity and cyclooxygenase-2 inhibition. interestingly they did not find the same effects in pure caffeine.[71] other in vitro investigations also record the ability of caffeine to neutralize singlet oxygen and oxygen radicles and to decrease subsequent lipid peroxidation. [72,73] more recent work has actually identified the caffeine metabolites: 1-methylxanthine, 1methyl uric acid, and 1,7-dimethyl uric acid as the real facilitators of this antioxidant activity. [74,75] these results support those of the study by silverberg et al, where the topical caffeine exerted a protective effect against ros-damage, but not through an antioxidizing effect (there was a time delay in action), presumably because it had not gone skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 64 through the systemic circulation and was not turned into its metabolites by hepatic microsomes. [65,76] patients with ad are particularly vulnerable to oxidative stress, as their immune dysfunction and barrier impairment cause chronic inflammation. [1] in this already sensitive environment, any additional oxidative dna or organelle damage would directly defect the physical barrier further, as well as induce more pro-inflammatory cytokines. [77] those, in turn, would produce more ros and would exacerbate the pruritus and physical damage, and the vicious cycle continues.[77] tsukahara et al present that children with acute ad exacerbations had abnormally elevated markers of oxidative stress, oxidative dna damage, and lipid peroxidation, compared to their healthy counterparts.[78] ros are very likely contributors in the development of psoriasis, as well, as redoxsensitive transduction systems are known to be implicated in its pathogenesis. [79-82] additionally, administering antioxidants has proven useful in the treatment of psoriasis.[83,84] this suggests a possible role of caffeine and its metabolites in the treatment of ad and psoriasis, through an ros-related mechanism. caffeine is usually used as the model for hydrophilic compounds in penetration studies; hence, much data establishes caffeine’s skin penetration from work both in vivo and in vitro. absorption of this highly water-soluble compound is unaffected by skin thickness, and was even shown to penetrate through hair follicles at higher speeds than through the inter-follicular epidermis.[85,86] delivering this compound in hydrophilic-lipophilic nanoemulsions, solid lipid nanoparticles, and the addition of chemical penetration enhancers all further heighten its permeation.[87-89] it is expected that damage of the stratum corneum, which usually protects the skin, would cause an increase in permeability. work by rubio et al shows that as skin barrier impairment increases, the rate of caffeine absorption increases exponentially. [90] this is not true for all compounds, as they also found that the increase in the case of salicylic acid is only linear.[90] with barrier dysfunction underpinning the pathogenesis of ad, these results further promote caffeine as a potential part of the therapy.[1] because we do not fully understand neither the pathogeneses of these diseases, nor the thorough pharmacology of this compound, we are only left to hypothesize on its possible modes of action in each case; but what we do know is that it is useful. we know that it is effective in inhibiting dna repair and inducing sound apoptosis of uv-damaged cells. we know that it can reduce injurious necrosis of ros-damaged cells. we know that it can help reduce inflammation by raising intracellular camp levels of cutaneous and peripheral leukocytes. finally, we know that its metabolites can neutralize oxidants in the body. all of these effects, combined, may act to reduce inflammation caused by internal and external sources, which is particularly valuable in inflammatory cutaneous disorders like psoriasis and atopic dermatitis. in fact, because the vast majority of skin diseases have at least some degree of inflammation, we may see caffeine supplementing the penetration discussion skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 65 therapy of others in the future. more research is needed to fully elucidate its potential, but so far results are promising. caffeine is a cheaper, safer alternative that could complement the long-term therapy of ad and psoriasis patients. conflict of interest disclosures: none. funding: none. corresponding author: mais alashqar, md alfaisal university riyadh, saudi arabia maisalashqar@gmail.com references: 1. rudikoff, d., cohen, s. r., & scheinfeld, n. (2014). atopic dermatitis and eczematous disorders. boca raton: crc press, taylor & francis group. 2. leung, d. y., & bieber, t. (2003). atopic dermatitis. the lancet,361(9352), 151-160. doi:10.1016/s0140-6736(03)12193-9 3. margolis, j. s., abuabara, k., bilker, w., hoffstad, o., & margolis, d. j. (2014). persistence of mild to moderate atopic dermatitis. jama dermatology, 150(6), 593-600. 4. nutten, s. (2015). atopic dermatitis: global epidemiology and risk factors. annals of nutrition and metabolism, 66(suppl. 1), 8-16. 5. rachakonda, t. d., schupp, c. w., & armstrong, a. w. (2014). psoriasis prevalence among adults in the united states. journal of the american academy of dermatology, 70(3), 512516. 6. sawai, t., ikai, k., & uehara, m. (1995). elevated cyclic adenosine monophosphate phosphodiesterase activity in peripheral blood mononuclear leucocytes from children with atopic dermatitis. british journal of dermatology, 132(1), 22-24. 7. salpietro, d. c., naccari, f., polimeni, i., & pellegrino, c. (1998). reduced plasma c-amp levels in children with atopic dermatitis. pediatric allergy and immunology : official publication of the european society of pediatric allergy and immunology, 9(3), 130132. doi:10.1111/j.1399-3038.1998.tb00358.x 8. hanifin, j. m., chan, s. c., cheng, j. b., tofte, s. j., henderson, w. r., kirby, d. s., & weiner, e. s. (1996). type 4 phosphodiesterase inhibitors have clinical and in vitro anti-inflammatory effects in atopic dermatitis. journal of investigative dermatology,107(1), 51-56. doi:10.1111/1523-1747.ep12297888 9. butler, j. m., chan, s. c., stevens, s., & hanifin, j. m. (1983). increased leukocyte histamine release with elevated cyclic ampphosphodiesterase activity in atopic dermatitis. journal of allergy and clinical immunology, 71(5), 490-497. 10. grewe, s. r., chan, s. c., & hanifin, j. m. (1982). elevated leukocyte cyclic amp— phosphodiesterase in atopic disease: a possible mechanism for cyclic amp—agonist hyporesponsiveness. journal of allergy and clinical immunology, 70(6), 452-457. 11. chan, s. c., reifsnyder, d., beavo, j. a., & hanifin, j. m. (1993). immunochemical characterization of the distinct monocyte cyclic amp-phosphodiesterase from patients with atopic dermatitis. journal of allergy and clinical immunology, 91(6), 1179-1188. 12. levy, j., zhou, d. m., & zippin, j. h. (2016). cyclic adenosine monophosphate signaling in inflammatory skin disease. journal of clinical and experimental dermatology research, 7(326), 2. 13. hanifin, j. m., & chan, s. c. (1995). monocyte phosphodiesterase abnormalities and mailto:maisalashqar@gmail.com skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 66 dysregulation of lymphocyte function in atopic dermatitis. journal of investigative dermatology, 105(1), s84-s88. 14. paller, a. s., tom, w. l., lebwohl, m. g., blumenthal, r. l., boguniewicz, m., call, r. s., ... & spellman, m. c. (2016). efficacy and safety of crisaborole ointment, a novel, nonsteroidal phosphodiesterase 4 (pde4) inhibitor for the topical treatment of atopic dermatitis (ad) in children and adults. journal of the american academy of dermatology, 75(3), 494-503. 15. ahluwalia, j., udkoff, j., waldman, a., borok, j., & eichenfield, l. f. (2017). phosphodiesterase 4 inhibitor therapies for atopic dermatitis: progress and outlook. drugs. doi:10.1007/s40265-017-0784-3 16. felding, j., sørensen, m. d., poulsen, t. d., larsen, j., andersson, c., refer, p., ... & hegardt, p. (2014). discovery and early clinical development of 2-{6-[2-(3, 5-dichloro-4-pyridyl) acetyl]-2, 3-dimethoxyphenoxy}-npropylacetamide (leo 29102), a soft-drug inhibitor of phosphodiesterase 4 for topical treatment of atopic dermatitis. journal of medicinal chemistry, 57(14), 5893–5903. 17. hanifin, j. m., chan, s. c., cheng, j. b., tofte, s. j., henderson, w. r., kirby, d. s., & weiner, e. s. (1996). type 4 phosphodiesterase inhibitors have clinical and in vitro anti-inflammatory effects in atopic dermatitis. journal of investigative dermatology, 107(1), 51-56. 18. samrao, a., berry, t. m., goreshi, r., & simpson, e. l. (2012). a pilot study of an oral phosphodiesterase inhibitor (apremilast) for atopic dermatitis in adults. archives of dermatology, 148(8), 890-897. 19. frateschi, s., camerer, e., crisante, g., rieser, s., membrez, m., charles, r. p., ... & rotman, s. (2011). par2 absence completely rescues inflammation and ichthyosis caused by altered cap1/prss8 expression in mouse skin. nature communications, 2, 161. 20. tsuji, f., aono, h., tsuboi, t., murakami, t., enomoto, h., mizutani, k., & inagaki, n. (2010). role of leukotriene b4 in 5-lipoxygenase metabolite-and allergy-induced itch-associated responses in mice. biological and pharmaceutical bulletin, 33(6), 1050-1053. 21. andoh, t., & kuraishi, y. (2014). antipruritic mechanisms of topical e6005, a phosphodiesterase 4 inhibitor: inhibition of responses to proteinase-activated receptor 2 stimulation mediated by increase in intracellular cyclic amp. journal of dermatological science,76(3), 206-213. doi:10.1016/j.jdermsci.2014.10.005 22. wakita, h., ohkuro, m., ishii, n., hishinuma, i., & shirato, m. (2015). a putative antipruritic mechanism of the phosphodiesterase-4 inhibitor e6005 by attenuating capsaicin-induced depolarization of c-fibre nerves. experimental dermatology,24(3), 215-216. doi:10.1111/exd.12606 23. andoh, t., yoshida, t., & kuraishi, y. (2014). topical e6005, a novel phosphodiesterase 4 inhibitor, attenuates spontaneous itch-related responses in mice with chronic atopy-like dermatitis. experimental dermatology,23(5), 359-361. doi:10.1111/exd.12377 24. serezani, c. h., ballinger, m. n., aronoff, d. m., & peters-golden, m. (2008). cyclic amp: master regulator of innate immune cell function. american journal of respiratory cell and molecular biology, 39(2), 127-132. 25. dina coronado, b. s., & zane, l. t. (2016). crisaborole topical ointment, 2%: a nonsteroidal, topical, anti-inflammatory phosphodiesterase 4 inhibitor in clinical development for the treatment of atopic dermatitis. j drugs dermatol, 15(4), 390-396. skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 67 26. grewe, s. r., chan, s. c., & hanifin, j. m. (1982). elevated leukocyte cyclic amp— phosphodiesterase in atopic disease: a possible mechanism for cyclic amp—agonist hyporesponsiveness. journal of allergy and clinical immunology, 70(6), 452-457. 27. qi, x. f., kim, d. h., yoon, y. s., li, j. h., song, s. b., jin, d., ... & lee, k. j. (2009). the adenylyl cyclase-camp system suppresses tarc/ccl17 and mdc/ccl22 production through p38 mapk and nf-κb in hacat keratinocytes. molecular immunology, 46(10), 1925-1934. 28. hanifin, j. m., & chan, s. c. (1995). monocyte phosphodiesterase abnormalities and dysregulation of lymphocyte function in atopic dermatitis. journal of investigative dermatology, 105(1), s84-s88. 29. menter, a., ryan, c., & menter, a. (2017). psoriasis. boca raton, fl: crc press, taylor & francis group. 30. morris, a., rogers, m., fischer, g., & williams, k. (2001). childhood psoriasis: a clinical review of 1262 cases. pediatric dermatology, 18(3), 188-198. 31. grewal, i. s. (2009). emerging protein biotherapeutics. boca raton: crc press. 32. voorhees, j. j., duell, e. a., bass, l. j., powell, j. a., & harrell, e. r. (1972). decreased cyclic amp in the epidermis of lesions of psoriasis. archives of dermatology, 105(5), 695-701. 33. voorhees, j. j., stawiski, m., duell, e. a., haddox, m. k., & goldberg, n. d. (1973). increased cyclic gmp and decreased cyclic amp levels in the hyperplastic, abnormally differentiated epidermis of psoriasis. life sciences,13(6), 639-653. doi:10.1016/00243205(73)90281-6 34. adachi, k., iizuka, h., halprin, k. m., & levine, v. (1980). epidermal cyclic amp is not decreased in psoriasis lesions. the journal of investigative dermatology, 74(2), 74-76. 35. herlin, t., & kragballe, k. (1981). enhanced monocyte and neutrophil cytotoxicity and normal cyclic nucleotide levels in severe psoriasis. british journal of dermatology, 105(4), 405-414. 36. iizuka, h., & ohkawara, a. (1986). “ischemic” rise of epidermal cyclic amp is a beta-adrenergic adenylate cyclase-dependent process. journal of investigative dermatology, 86(3), 271-274. 37. wittmann, m., & helliwell, p. s. (2013). phosphodiesterase 4 inhibition in the treatment of psoriasis, psoriatic arthritis and other chronic inflammatory diseases. dermatology and therapy, 3(1), 1-15. 38. gooderham, m., & papp, k. (2015). selective phosphodiesterase inhibitors for psoriasis: focus on apremilast. biodrugs,29(5), 327-339. doi:10.1007/s40259-015-0144-3 39. dong, c., virtucio, c., zemska, o., baltazar, g., zhou, y., baia, d., . . . jarnagin, k. (2016). treatment of skin inflammation with benzoxaborole phosphodiesterase inhibitors: selectivity, cellular activity, and effect on cytokines associated with skin inflammation and skin architecture changes. journal of pharmacology and experimental therapeutics,358(3), 413-422. doi:10.1124/jpet.116.232819 40. tenor, h., hatzelmann, a., church, m. k., schudt, c., & shute, j. k. (1996). effects of theophylline and rolipram on leukotriene c4 (ltc4) synthesis and chemotaxis of human eosinophils from normal and atopic subjects. british journal of pharmacology, 118(7), 1727-1735. 41. samrao, a., berry, t. m., goreshi, r., & simpson, e. l. (2012). a pilot study of an oral phosphodiesterase inhibitor (apremilast) for atopic dermatitis in adults. archives of dermatology, 148(8), 890-897. skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 68 42. schafer, p. h., parton, a., gandhi, a. k., capone, l., adams, m., wu, l., ... & baillie, g. s. (2010). apremilast, a camp phosphodiesterase ‐ 4 inhibitor, demonstrates anti ‐ inflammatory activity in vitro and in a model of psoriasis. british journal of pharmacology, 159(4), 842-855. 43. nazarian, r., & weinberg, j. m. (2009). an2728, a pde4 inhibitor for the potential topical treatment of psoriasis and atopic dermatitis. current opinion in investigational drugs (london, england: 2000), 10(11), 12361242. 44. rafael, a., & torres, t. (2016). topical therapy for psoriasis: a promising future. focus on jak and phosphodiesterase-4 inhibitors. european journal of dermatology, 26(1), 3-8. 45. kaplan, r. j., daman, l., shereff, r., rosenberg, e. w., & robinson, h. (1976). treatment of atopic dermatitis with topically applied caffeine. archives of dermatology, 112(6), 880-881. 46. kaplan, r. j., daman, l., rosenberg, e. w., & feigenbaum, s. (1977). treatment of atopic dermatitis with topically applied caffeine—a follow-up report. archives of dermatology, 113(1), 107-107. 47. kaplan, r. j., daman, l., rosenberg, e. w., & feigenbaum, s. (1978). topical use of caffeine with hydrocortisone in the treatment of atopic dermatitis. archives of dermatology, 114(1), 6062. 48. furue, m., terao, h., rikihisa, w., urabe, k., kinukawa, n., nose, y., & koga, t. (2003). clinical dose and adverse effects of topical steroids in daily management of atopic dermatitis. british journal of dermatology, 148(1), 128-133. 49. vali, a., asilian, a., khalesi, e., khoddami, l., shahtalebi, m., & mohammady, m. (2005). evaluation of the efficacy of topical caffeine in the treatment of psoriasis vulgaris. journal of dermatological treatment, 16(4), 234-237. 50. maréchal, a., & zou, l. (2013). dna damage sensing by the atm and atr kinases. cold spring harbor perspectives in biology, 5(9), a012716. 51. tibbetts, r. s., brumbaugh, k. m., williams, j. m., sarkaria, j. n., cliby, w. a., shieh, s. y., ... & abraham, r. t. (1999). a role for atr in the dna damage-induced phosphorylation of p53. genes & development, 13(2), 152-157. 52. lehmann, a. r. (1972). effect of caffeine on dna synthesis in mammalian cells. biophysical journal, 12(10), 1316-1325. 53. khanna, k. k., & jackson, s. p. (2001). dna double-strand breaks: signaling, repair and the cancer connection. nature genetics, 27(3), 247. 54. charrier, j. d., durrant, s. j., golec, j. m., kay, d. p., knegtel, r. m., maccormick, s., ... & rutherford, a. p. (2011). discovery of potent and selective inhibitors of ataxia telangiectasia mutated and rad3 related (atr) protein kinase as potential anticancer agents. journal of medicinal chemistry, 54(7), 2320-2330. 55. pires, i. m., olcina, m. m., anbalagan, s., pollard, j. r., reaper, p. m., charlton, p. a., ... & hammond, e. m. (2012). targeting radiationresistant hypoxic tumour cells through atr inhibition. british journal of cancer, 107(2), 291. 56. fokas, e., prevo, r., pollard, j. r., reaper, p. m., charlton, p. a., cornelissen, b., ... & muschel, r. j. (2012). targeting atr in vivo using the novel inhibitor ve-822 results in selective sensitization of pancreatic tumors to radiation. cell death & disease, 3(12), e441. 57. rauth, a. m. (1967). evidence for darkreactivation of ultraviolet light damage in mouse l cells. radiation research, 31(1), 121-138. 58. domon, m., & rauth, a. m. (1969). ultravioletlight irradiation of mouse l cells: effects on cells skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 69 in the dna synthesis phase. radiation research, 40(2), 414-429. 59. m. domon, b. barton, a. porte & a.m. rauth (1970) the interaction of caffeine with ultraviolet-light-irradiated dna, international journal of radiation biology and related studies in physics, chemistry and medicine, 17:4, 395399, doi: 10.1080/09553007014550481 60. roberts, j. j., sturrock, j. e., & ward, k. n. (1974). the enhancement by caffeine of alkylation-induced cell death, mutations and chromosomal aberrations in chinese hamster cells, as a result of inhibition of post-replication dna repair. mutation research/fundamental and molecular mechanisms of mutagenesis, 26(2), 129-143. 61. gaudin, d., & yielding, k. l. (1969). response of a “resistant” plasmacytoma to alkylating agents and x-ray in combination with the “excision repair inhibitors caffeine and chloroquine∗. proceedings of the society for experimental biology and medicine, 131(4), 1413-1416. 62. rauth, a. m., barton, b., & lee, c. p. y. (1970). effects of caffeine on l-cells exposed to mitomycin c. cancer research, 30(11), 27242729. 63. sarkaria, j. n., busby, e. c., tibbetts, r. s., roos, p., taya, y., karnitz, l. m., & abraham, r. t. (1999). inhibition of atm and atr kinase activities by the radiosensitizing agent, caffeine. cancer research, 59(17), 4375-4382. 64. zajdela, f., & latarjet, r. (1973). inhibitory effect of caffeine on the induction of cutaneous cancers by ultraviolet rays in the mouse. comptes rendus hebdomadaires des séances de l'académie des sciences. série d: sciences naturelles, 277(12), 1073-1076. 65. silverberg, j. i., patel, m., brody, n., & jagdeo, j. (2012). caffeine protects human skin fibroblasts from acute reactive oxygen speciesinduced necrosis. journal of drugs in dermatology: jdd, 11(11), 1342-1346. 66. rock, k. l., & kono, h. (2008). the inflammatory response to cell death. annual review of pathology, 3, 99–126. http://doi.org/10.1146/annurev.pathmechdis.3 .121806.151456 67. muralidharan, s., & mandrekar, p. (2013). cellular stress response and innate immune signaling: integrating pathways in host defense and inflammation. journal of leukocyte biology, 94(6), 1167-1184. 68. abel, e. l., hendrix, s. o., mcneeley, s. g., johnson, k. c., rosenberg, c. a., mossavarrahmani, y., ... & kruger, m. (2007). daily coffee consumption and prevalence of nonmelanoma skin cancer in caucasian women. european journal of cancer prevention, 16(5), 446-452. 69. song, f., qureshi, a. a., & han, j. (2012). increased caffeine intake is associated with reduced risk of basal cell carcinoma of the skin. cancer research, 72(13), 3282-3289. 70. loftfield, e., freedman, n. d., graubard, b. i., hollenbeck, a. r., shebl, f. m., mayne, s. t., & sinha, r. (2015). coffee drinking and cutaneous melanoma risk in the nih-aarp diet and health study. journal of the national cancer institute, 107(2), dju421. 71. chu, y. f., chen, y., brown, p. h., lyle, b. j., black, r. m., cheng, i. h., ... & prior, r. l. (2012). bioactivities of crude caffeine: antioxidant activity, cyclooxygenase-2 inhibition, and enhanced glucose uptake. food chemistry, 131(2), 564-568. 72. devasagayam, t. p. a., kamat, j. p., mohan, h., & kesavan, p. c. (1996). caffeine as an antioxidant: inhibition of lipid peroxidation induced by reactive oxygen species. biochimica et biophysica acta (bba)biomembranes, 1282(1), 63-70. skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 70 73. shi, x., dalal, n. s., & jain, a. c. (1991). antioxidant behaviour of caffeine: efficient scavenging of hydroxyl radicals. food and chemical toxicology, 29(1), 1-6. 74. lee, c. (2000). antioxidant ability of caffeine and its metabolites based on the study of oxygen radical absorbing capacity and inhibition of ldl peroxidation. clinica chimica acta, 295(1), 141154. 75. scurachio, r. s., mattiucci, f., santos, w. g., skibsted, l. h., & cardoso, d. r. (2016). caffeine metabolites not caffeine protect against riboflavin photosensitized oxidative damage related to skin and eye health. journal of photochemistry and photobiology b: biology, 163, 277-283. 76. berthou, f. r. a. n. c. o. i. s., flinois, j. p., ratanasavanh, d., beaune, p. h. i. l. l. i. p. e., riche, c. h. r. i. s. t. i. a. n., & guillouzo, a. n. d. r. e. (1991). evidence for the involvement of several cytochromes p-450 in the first steps of caffeine metabolism by human liver microsomes. drug metabolism and disposition, 19(3), 561-567. 77. ji, h., & li, x. (2016). oxidative stress in atopic dermatitis. oxidative medicine and cellular longevity, 2016, 1-8. doi:10.1155/2016/2721469 78. tsukahara, h., shibata, r., ohshima, y., todoroki, y., sato, s., ohta, n., ... & mayumi, m. (2003). oxidative stress and altered antioxidant defenses in children with acute exacerbation of atopic dermatitis. life sciences, 72(22), 25092516. 79. zhou, q., mrowietz, u., & rostami-yazdi, m. (2009). oxidative stress in the pathogenesis of psoriasis. free radical biology and medicine, 47(7), 891-905. 80. gabr, s. a., & al-ghadir, a. h. (2012). role of cellular oxidative stress and cytochrome c in the pathogenesis of psoriasis. archives of dermatological research, 304(6), 451-457. 81. yildirim, m., inaloz, h. s., baysal, v., & delibas, n. (2003). the role of oxidants and antioxidants in psoriasis. journal of the european academy of dermatology and venereology, 17(1), 34-36. 82. api, h., & atik, u. (2003). oxidant/antioxidant status in patients with psoriasis. yonsei medical journal, 44(6), 987990. 83. lin, x., & huang, t. (2016). oxidative stress in psoriasis and potential therapeutic use of antioxidants. free radical research, 50(6), 585595. 84. kharaeva, z., gostova, e., de luca, c., raskovic, d., & korkina, l. (2009). clinical and biochemical effects of coenzyme q 10, vitamin e, and selenium supplementation to psoriasis patients. nutrition, 25(3), 295-302. 85. otberg, n., patzelt, a., rasulev, u., hagemeister, t., linscheid, m., sinkgraven, r., ... & lademann, j. (2008). the role of hair follicles in the percutaneous absorption of caffeine. british journal of clinical pharmacology, 65(4), 488-492. 86. wilkinson, s. c., maas, w. j., nielsen, j. b., greaves, l. c., van de sandt, j. j., & williams, f. m. (2006). interactions of skin thickness and physicochemical properties of test compounds in percutaneous penetration studies. international archives of occupational and environmental health, 79(5), 405-413. 87. abd, e., namjoshi, s., mohammed, y. h., roberts, m. s., & grice, j. e. (2015). synergistic skin penetration enhancer and nanoemulsion formulations promote the human epidermal permeation of caffeine and naproxen. journal of pharmaceutical sciences. 88. jagannath, s. s., manohar, s. d., & bhanudas, s. r. (2013). chemical penetration enhancers—a skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 71 review. world journal of pharmacy and pharamceutical sciences, 3(2), 1068-80. 89. abd, e., roberts, m. s., & grice, j. e. (2016). a comparison of the penetration and permeation of caffeine into and through human epidermis after application in various vesicle formulations. skin pharmacology and physiology, 29(1), 24-30. 90. rubio, l., alonso, c., lópez, o., rodríguez, g., coderch, l., notario, j., ... & parra, j. l. (2011). barrier function of intact and impaired skin: percutaneous penetration of caffeine and salicylic acid. international journal of dermatology, 50(7), 881-889. skin november 2017 volume 1 issue 3 copyright 2017 the national society for cutaneous medicine 143 therapeutic tips clinically important considerations with the use of oral doxycycline james q. del rosso, do a,b,c a touro university nevada, henderson, nv b jdr dermatology research, las vegas, nv c thomas dermatology, las vegas, nv tetracyclines are the most commonly prescribed antibiotics in dermatology in the united states (us). 1 these oral agents, predominantly doxycycline and minocycline, comprise approximately 75% of all antibiotic prescriptions written by dermatologists, with dermatologists accounting for approximately 20% of all tetracyclines prescribed among all physicians in the us. 1-4 both doxycycline and minocycline are highly lipophilic, which explains their marked skin penetration, with the reasonable scientific assumption that high concentrations are achieved within the lipid-rich pilosebaceous unit. 3 skin penetration is important for treatment of both cutaneous infections and non-infectious dermatoses, such as acne vulgaris (av), rosacea, and other inflammatory dermatologic disorders that are treated with tetracycline agents; pilosebaceous unit penetration is important in acne therapy as follicular propionibacterium acnes is one of the therapeutic targets in av. 2-8 both doxycycline and minocycline exhibit a broad range of activity against several bacterial organisms relevant to commonly encountered skin conditions, such as p acnes (av) and staphylococcus aureus, including methicillin-resistant strains. 2-5,9 importantly, tetracyclines also exhibit multiple biologic effects unrelated to their antibiotic activity which appear to play important mechanistic roles in the treatment of common facial inflammatory dermatoses, abstract tetracyclines are the most commonly prescribed oral antibiotics in dermatology. they are used to treat bothcutaneous infections and non-infectious inflammatory disorders, the latter often with chronic therapy. doxycycline may be favored by some dermatologists over minocycline due to a lower risk of certain adverse reactions, especially some with systemic manifestations. the major adverse events that are more common with doxycycline are gastrointestinal side effects, including pill esophagitis, and phototoxicity. this article reviews practical tips when prescribing oral doxycycline, emphasizing suggestions to optimize therapeutic success and reduce untoward reactions. introduction skin november 2017 volume 1 issue 3 copyright 2017 the national society for cutaneous medicine 144 such as av and rosacea, and less common diseases such as bullous pemphigoid and granulomatous disorders. 2,6-8,10,11 it is important to recognize that although doxycycline and minocycline are within the same general class of antibiotics, namely tetracyclines, there are several clinically relevant differences between these drugs, especially in their potential adverse reaction profiles. 2-5,12 this article specifically reviews clinically relevant considerations when prescribing oral doxycycline, with emphasis on four important practical tips to optimize therapeutic success and avoid adverse sequelae. doxycycline is available as either doxycycline hyclate or doxycycline monohydrate, with no clinical evidence of differences in efficacy or safety between the two salts of doxycycline when administered as immediate-release antibiotic-dose formulations . 2,13,14 enteric-release doxycycline and a specific small-tablet brand doxycycline have been shown to exhibit similar pharmacokinetic profiles, with both demonstrating very similar low rates of potential for gastrointestinal (gi) aes, such as nausea, abdominal discomfort/pain, and/or vomiting, even in the absence of food. 14 importantly, however, concurrent administration with food further decreases the risk of gi-related aes. 14 enteric-coated doxycycline has been shown to markedly reduce the risk of gi-related aes compared to a standard brand immediate-release doxycycline formulation. 15 subantibiotic dose doxycycline, administered as a specific modified-release 40 mg capsule once daily for papulopustular rosacea, was associated with a marked decrease of gi-related aes as compared to immediate-release doxycycline 100 mg once daily; none of the study subjects receiving subantibiotic dose doxycycline experienced nausea, abdominal discomfort, vomiting, or diarrhea. 16 doxycycline is a leading cause of pill esophagitis, which occurs when patients do not properly administer the drug; in many cases this was associated with inadequate patient education. 2,17,18 esophageal inflammation, erosions, and ulcerations have been described with this entity at all levels within the esophagus. the most commonly associated symptoms are odynophagia, retrosternal pain, and dysphagia. 17,18 in almost all cases, pill esophagitis occurred in patients who reported a history of swallowing their oral doxycycline with only a small amount of water, and taking the medication in a recumbent position, or both. 2,17,18 with proper patient education and compliance, pill esophagitis can be prevented. it is important that patients be instructed to ingest oral doxycycline with a large glass of water, to be in an upright position while ingesting the medication, and to preferably administer during or immediately after a meal. 2,14,17,18 although the potential for photoxicity associated with oral doxycycline use is wellrecognized, a recent systematic review of phototoxicity of doxycycline identified mostly tip #1: consider the formulation when prescribing oral doxycycline tip #2: reduce the potential for “pill esophagitis” by optimizing patient education on proper administration of oral doxycycline tip #3: consider potential doserelated phototoxicity and employ preventative measures to reduce risk skin november 2017 volume 1 issue 3 copyright 2017 the national society for cutaneous medicine 145 case reports and only a few studies that shed light on this topic. 19 the potential for phototoxicity is not dependent on gender, age, or duration of therapy, but rather the intensity and duration of ultraviolet light (uv) exposure, with fitzpatrick skin types i and ii exhibiting an enhanced risk. 19,20 phototoxic skin reactions or photo-onycholysis may occur. the potential for phototoxicity induced by doxycycline appears to be doserelated; one series following patients treated with doxycycline over a 2 year period (n=106) reported phototoxicity in 42% (32/76) of those treated with 200 mg/day and in 20% (6/30) of those treated with 150 mg/day. 21 the reactions did not typically occur during usual daily sun exposure, but rather during periods of much greater uv exposure while on vacation in a sunny climate. 21 it is important to recognize that tetracyclinerelated phototoxicity is mediated in the long wavelength of the uva spectrum (340-400 nm). 19 sunscreens that absorb uva light only in the shorter wavelength end of the uva spectrum, such as oxybenzone (340360 nm), are inadequate in preventing doxycycline-induced phototoxic reactions. 19,22 it is prudent in patients treated with oral doxycycline to educate them on principles of photoprotection, including the use and periodic re-application of a sunscreen that filters across the entire uva spectrum, protective clothing, and avoidance of intense mid-day sun exposure whenever possible. 19 use of oral polypodium leucotomos extract (ple) to further supplement sunscreen use and other photoprotection measures may further reduce the risk of phototoxic effects; this suggestion is based on theoretical consideration of data supporting the ameliorating effects of ple after uva or uvb exposures. 23 for treatment of chronic inflammatory disorders such as av, it is reasonable to suggest to patients to temporarily discontinue oral doxycycline use over the short duration of a vacation to be spent outdoors in a sunny climate or location of high uv exposure. 21 the overall safety profile of tetracycline antibiotics is very favorable. 2,4,5,12 the most common potential aes associated with oral doxycycline use are gi-related aes, including pill esophagitis, and phototoxicity. 2,5,12,18,18 both are reasonably preventable as explained above. doxycycline use has not been associated with some of the potential aes encountered with utilization of oral minocycline, such as vestibular aes (eg vertigo, dizziness), cutaneous and/or mucosal hyperpigmentation, and autoimmune reactions (eg hepatitis, drug-induced lupuslike syndrome), the latter being rare but with systemic manifestations; drug hypersensitivity syndrome (drug reaction with eosinophilia and systemic symptoms [dress]) has been reported much more commonly with oral minocycline, and appears to be very rare and of negligible risk with oral doxycycline. 2-5,12-14 the rate of acute vestibular aes associated with oral minocycline use has been shown to be less with use of weight-based dosing (1 mg/kg/day) with a specific extended-release minocycline tablet formulation. 2 benign intracranial hypertension (pseudotumor cerebri), often presenting with intractable cephalgia, nausea/vomiting, photophobia, and/or diplopia, is a rare side effect that may occur after use of any tetracycline agent, is diagnosed by the presence of papilledema, and warrants early detection and tip #4: evaluate the adverse reaction profile when prescribing oral doxycycline skin november 2017 volume 1 issue 3 copyright 2017 the national society for cutaneous medicine 146 intervention to reduce the risk of vision loss. 2 when treating papulopustular rosacea with an oral agent, it has been suggested that subantibiotic dose doxycycline (40 mg mr capsule once daily or 20 mg twice daily) be used initially, as there are data demonstrating efficacy comparable to oral doxycycline 100 mg daily with fewer girelated aes, and avoidance of antibiotic resistance due to absence of selection pressure. 2,16,24 doxycycline is a commonly prescribed oral antibiotic in dermatology, used for treatment of uncomplicated cutaneous infections, such as those caused by mrsa, and some noninfectious inflammatory dermatoses, such as av, rosacea, and bullous pemphigoid. pill esophagitis and phototoxicity are two preventable aes that can occur with use of oral doxycycline. ingestion with a large glass of water and food while maintaining an upright position can prevent pill esophagitis. enteric-coated and a special small tablet formulation of doxycycline are both associated with a low risk of gi-related aes. prevention of doxycycline-induced phototoxicity warrants photoprotection measures that includes use of a sunscreen that filters out the full uva spectrum. oral doxycycline is essentially devoid of certain side effects associated with oral minocycline use, such as vertigo/dizziness, hyper pigmentation, drug hypersensitivity syndrome, and autoimmune reactions. subantibiotic dose doxycycline is a preferred oral therapy choice for papulopustular rosacea due to low potential for aes and avoidance of antibiotic resistance. conflict of interest: none. disclosures: dr. del rosso is a consultant, investigator, and/or speaker for allergan, aqua/almirall, bayer, biopharmx, celgene, cipher (innocutis), cutanea, dermira, exeltis, ferndale, foamix, galderma, genentech, leopharma, novan, pfizer (anacor), pharmaderm, promius, regeneron, sanofi/genzyme, sebacia, sunpharma, taro, unilever, valeant (ortho dermatologics), and viamet. this article was developed and written solely by the author. the author did not receive any form of compensation, either directly or indirectly, from any company or agency related to the development, authorship, or publication of this article. funding: none. corresponding author: james q. del rosso, do jdr dermatology research 9080 west post road suite 100 las vegas, nevada 89148 702-331-4123 jqdelrosso@yahoo.com references: 1. del rosso jq, webster gf, rosen t, et al. status report from the scientific panel on antibiotic use in dermatology of the american acne and rosacea society part 1: antibiotic prescribing patterns, sources of antibiotic exposure, antibiotic consumption and emergence of antibiotic resistance, impact of alterations in antibiotic prescribing, and clinical sequelae of antibiotic use. j clin aesthet dermatol. 2016;9(4):18–24. 2. kim s, michaels bd. kim gk, del rosso jq. systemic antibacterial agents. in: wolverton se, ed, comprehensive dermatologic drug therapy, 3 rd edition, elsevier-saunders, philadelphia, pennsylvania, 2013, pp 61-98. 3. leyden jj, del rosso jq. oral antibiotic therapy for acne vulgaris: pharmacokinetic and pharmacodynamic perspectives. j clin aesthet dermatol. 2011;4(2):40-47. 146 summary skin november 2017 volume 1 issue 3 copyright 2017 the national society for cutaneous medicine 147 4. del rosso jq. topical and oral antibiotics for acne vulgaris. semin cutan med surg. 2016;35(2):5761. 5. del rosso jq, kim gk. optimizing use of oral antibiotics in acne vulgaris. dermatol clin. 2009;27(1):33-42. 6. korting hc, schollmann c. tetracycline actions relevant to rosacea treatment. skin pharmacol physiol. 2009;22(6):287-294. 7. webster gf, del rosso jq. anti-inflammatory activity of tetracyclines. dermatol clin. 2007;25(2):133-135. 8. bhatia n. use of antibiotics for noninfectious dermatologic disorders. dermatol clin. 2009;27(1):85-89. 9. del rosso jq, rosen t, thiboutot d, et al. status report from the scientific panel on antibiotic use in dermatology of the american acne and rosacea society part 3: current perspectives on skin and soft tissue infections with emphasis on methicillin-resistant staphylococcus aureus, commonly encountered scenarios when antibiotic use may not be needed, and concluding remarks on rational use of antibiotics in dermatology. j clin aesthet dermatol. 2016;9(6):17–24. 10. del rosso jq. a status report on the use of subantimicrobial-dose doxycycline: a review of the biologic and antimicrobial effects of the tetracyclines. cutis. 2004;74(2):118-122. 11. sapadin an, fleischmajer r. tetracyclines: nonantibiotic properties and their clinical implications. j am acad dermatol. 2006;54(2):258-265. 12. del rosso jq. oral antibiotics. in: shalita ar, del rosso jq, webster gf, eds, acne vulgaris, informa healthcare, london, united kingdom, 2011, pp 113-124. 13. del rosso jq. systemic therapy for rosacea: focus on oral antibiotic therapy and safety. cutis. 2000;66(4 suppl):7-13. 14. del rosso jq. oral doxycycline in the management of acne vulgaris: current perspectives on clinical use and recent findings with a new double-scored small tablet formulation. j clin aesthet dermatol. 2015;8(5):19-26. 15. berger rs. a double-blind, multiple-dose, placebo-controlled, cross-over study to compare the incidence of gastrointestinal complaints in healthy subjects given doryx r and vibramycin r. j clin pharmacol. 1988;28(4):367-370. 16. del rosso jq, schlessinger j, werschler p. comparison of anti-inflammatory dose doxycycline versus doxycycline 100 mg in the treatment of rosacea. j drugs dermatol. 2008;7(6):573-576. 17. kadayifci a, gulsen mt, koruk m, et al. doxycycline-induced pill esophagitis. dis esophagus. 2004;17(2):168-171. 18. dağ ms, öztürk za, akın i, et al. drug-induced esophageal ulcers: case series and the review of the literature. turk j gastroenterol. 2014;25(2):180-184. 19. goetze s, hiernickel c, elsner p. photoxicity of doxycycline. skin pharmacol physiol. 2017;30:7680. 20. yong ck, prendiville j, peacock dl, et al. an unusual presentation of doxycycline-induced photsoensitivity. pediatrics. 2000;106:e13. 21. layton am, cunliffe wj. phototoxic eruptions due to doxycycline – a dose-related phenomenon. clin exp dermatol. 1993;18:425427. 22. lim ds, murphy gm. high-level ultraviolet a photoprotection is needed to prevent doxycycline: lessons learned in east timor. br j dermatol. 2003;149:213-214. 23. del rosso jq. use of polypodium leucotomas extract in clinical practice: a primer for the clinician. j clin aesthet dermatol. 2016;9(5):3742. skin november 2017 volume 1 issue 3 copyright 2017 the national society for cutaneous medicine 148 24. del rosso jq, baldwin h, webster g, et al. american acne & rosacea society rosacea medical management guidelines. j drugs dermatol. 2008;7(6):531-533. introduction • in patients with psoriasis, assessment of body surface area (bsa) involvement is a common measure of disease severity1,2 — an acceptable response to treatment after 3 months is defined by the national psoriasis foundation as bsa ≤3%, whereas the target response to treatment at 3 months is defined as bsa ≤1%3 • deucravacitinib (bms-986165) is a novel, oral, allosteric inhibitor that selectively inhibits intracellular signaling by cytokines involved in psoriasis pathogenesis by binding to tyrosine kinase 2 (tyk2) at its pseudokinase domain rather than to the conserved active site in the kinase domain4,5 • in a phase 2 double-blind trial in patients with moderate to severe plaque psoriasis (pso; nct02931838), 67%–75% of patients treated with deucravacitinib at dosages of 3 or 6 mg twice daily (bid) or 12 mg once daily (qd) achieved psoriasis area and severity index 75 (pasi 75; ≥75% reduction from baseline pasi) at week 12 vs 7% of patients who received placebo (p<0.001)5 — additionally, more patients in the phase 2 trial treated with 3 mg bid, 6 mg bid, or 12 mg qd deucravacitinib reported normal or near-normal quality of life (qol) than placebo recipients (42%, 60%, and 64%, respectively, vs 4%)5 objective • the objective of this post hoc analysis of data from the phase 2 trial was to evaluate bsa changes over time as well as the relationship between bsa reductions and improvements in qol at week 12 methods patient population • adults with moderate to severe pso were randomized equally to 1 of 5 deucravacitinib dosages (3 mg every other day to 12 mg qd) or placebo — patients in the 3 most efficacious dose groups (3 mg bid [n=45], 6 mg bid [n=45], 12 mg qd [n=44]) and in the placebo group (n=45) were included in this analysis assessments • mean change from baseline in bsa over time — measurement of bsa involvement with skin lesions was estimated using the handprint method, with the size of a patient’s handprint representing ~1% of bsa involvement • percentage of patients who achieved bsa of ≤1% and ≤3% at week 12 • dermatology life quality index (dlqi; range, 0−30, with higher scores indicating worse qol) at week 12 in subgroups of patients with bsa ≤1% or ≤3% • patients who discontinued the trial early or had a missing value at any time point had outcomes imputed as a nonresponse at that time point, regardless of the status of response at the time of discontinuation results change from baseline in bsa over time • at baseline, bsa involvement was generally comparable across deucravacitinib dosage groups and the placebo group (mean [sd]: 3 mg bid (n=45), 24.5% [15.5%]; 6 mg bid (n=45), 24.8% [13.0%]; 12 mg qd (n=44), 20.6% [12.0%]; and placebo (n=45), 24.2% [13.3%]) • substantial improvements from baseline in mean bsa were observed over time with deucravacitinib treatment, with similar improvements observed in each of the 3 deucravacitinib dosage groups (figure 1) figure 1. mean change from baseline in bsa over time m e an c h an ge f ro m b as e li n e ( % ), s e time (weeks) 2 6 104 8 12 -25 -20 -15 -10 -5 0 0 placebo (n=45) 3 mg bid (n=45) 6 mg bid (n=45) 12 mg qd (n=44) bid, twice daily; bsa, body surface area; qd, once daily. percentage of patients who achieved bsa of ≤1% and ≤3% at week 12 • bsa ≤1% was achieved by approximately one-third of patients receiving deucravacitinib vs 0% of those receiving placebo (figure 2) — additionally, bsa ≤3% was achieved by approximately one-half of patients receiving deucravacitinib vs 2.2% receiving placebo • nearly 40% of patients achieved bsa ≤1 and nearly 60% achieved bsa ≤3 in the highest-responding deucravacitinib 12 mg qd group figure 2. percentage of patients with bsa involvement of ≤1% or ≤3% at week 12 p at ie n ts ( % ) 70 20 10 0 50 30 60 40 0/45n/n: 12/45 17/45 bsa ≤1% 0 26.7 37.8 38.6 2.2 51.1 44.4 56.8 bsa ≤3% 17/44 1/45 23/45 20/45 25/44 90 80 100 placebo 3 mg bid 6 mg bid 12 mg qd bid, twice daily; bsa, body surface area; qd, once daily. dlqi at week 12 according to level of bsa involvement • mean dlqi at week 12 was lower among patients with bsa ≤1% and ≤3% who received deucravacitinib compared with the placebo recipient with bsa ≤3% (figure 3) — mean dlqi at week 12 was also numerically lower in those patients who received a daily dose of 12 mg deucravacitinib (ie, 6 mg bid and 12 mg qd groups) than in those who received 6 mg daily doses (ie, 3 mg bid; figure 3) figure 3. mean* dlqi at week 12 according to level of bsa involvement m e an d lq i at w e e k 1 2 6 1 0 4 2 5 3 0/45n/n: 12/45 17/45 bsa ≤1% n/a 2.4 1.5 0.9 8.0 2.9 1.4 1.0 bsa ≤3% 17/44 1/45 23/45 20/45 25/44 8 7 9 placebo 3 mg bid 6 mg bid 12 mg qd bid, twice daily; bsa, body surface area; dlqi, dermatology life quality index; n/a, not applicable; qd, once daily. *error bars are sds. conclusions • this post hoc analysis indicates that deucravacitinib is associated with clinically meaningful decreases in bsa over time, and that clinically meaningful dlqi values were reported in patients who achieved bsa ≤1% and ≤3% • a substantial number of patients treated with deucravacitinib at the 3 highest tested doses achieved absolute and acceptable treat-totarget bsa values established by the national psoriasis foundation3 • five phase 3 trials in pso (nct03624127, nct03611751, nct04167462, nct03924427, and nct04036435) are currently evaluating the efficacy and safety of deucravacitinib in larger patient cohorts over a longer treatment period references 1. puig l et al. acta derm venereol. 2019;99:971-7. 2. spuls pi et al. j invest dermatol. 2010;130:933-43. 3. armstrong aw et al. j am acad dermatol. 2017;76:290-8. 4. burke jr et al. sci transl med. 2019;11:1-16. 5. papp k et al. n engl j med. 2018;379:1313-21. acknowledgments • this clinical trial was sponsored by bristol myers squibb. professional medical writing assistance from ann marie fitzmaurice, phd and editorial assistance were provided by peloton advantage, llc, an open health company, parsippany, nj, and were funded by bristol myers squibb. relationships and activities • am: advisory board: abbott labs, amgen, boehringer ingelheim, janssen biotech, leo pharma. consultant: abbott labs, amgen, eli lilly, janssen biotech, leo pharma, novartis, sun pharma, ucb. investigator: abbott labs, amgen, boehringer ingelheim, celgene, eli lilly, janssen biotech, leo pharma, merck, novartis, sun pharma, ucb. speaker: abbott labs, amgen, janssen biotech, leo pharma, sun pharma, ucb. grant: abbott labs, amgen, boehringer ingelheim, celgene, janssen biotech, leo pharma, merck, sun pharma. honoraria: abbott labs, amgen, boehringer ingelheim, eli lilly, janssen biotech, leo pharma, novartis, sun pharma, ucb. • ab: scientific advisor and/or clinical study investigator: abbvie, almirall, arena, athenex, boehringer ingelheim, bristol myers squibb, dermavant, eli lilly and company, forte, galderma, incyte, janssen, leo pharma, novartis, pfizer, rapt, regeneron, sanofi genzyme, sun pharma, ucb pharma. speaker: abbvie. • bs: honoraria or consultation fees: abbvie, almirall, amgen, arena, boehringer ingelheim, bristol myers squibb, celgene, dermavant, dermira, eli lilly, gsk, janssen, kyowa hakko kirin, leo pharma, medac, meiji seika pharma, novartis, ortho dermatologics, pfizer, regeneron, sanofi genzyme, sun pharma, ucb. speaker: abbvie, janssen, lilly, ortho dermatologics. scientific director: corrona psoriasis registry. investigator: abbvie, corrona psoriasis registry, dermavant, dermira. • cl: honoraria or consultation fees: abbvie, amgen, boehringer ingelheim, dermira, eli lilly, janssen, leo pharma, ortho dermatologics, pfizer, sandoz, ucb. speaker: amgen, abbvie, celgene, eli lilly, janssen, novartis, sun pharmaceuticals, ucb. investigator: abbvie, allergan, amgen, boehringer ingelheim, celgene, cellceutix, coherus, corrona psoriasis registry, dermira, eli lilly, galderma, glenmark, janssen, leo pharma, merck, novartis, novella, pfizer, sandoz, sienna, stiefel, ucb, wyeth. • mjc, rmk, sk, and sb: employees and shareholders of bristol myers squibb deucravacitinib (bms-986165), an oral, allosteric tyrosine kinase 2 inhibitor, reduces body surface area involvement and improves quality of life in patients with psoriasis alan menter,1 andrew blauvelt,2 bruce strober,3 matthew j. colombo,4 renata m. kisa,4 sudeep kundu,4 subhashis banerjee,4 craig leonardi5 1baylor university medical center, dallas, tx; 2oregon medical research center, portland, or; 3yale university, new haven, ct, and central connecticut dermatology research, cromwell, ct; 4bristol myers squibb, princeton, nj; 5saint louis university school of medicine, st. louis, mo presented at the 2020 fall clinical dermatology conference; october 29−november 1, 2020; virtual meeting and at las vegas, nevada http://www.globalbmsmedinfo.com this poster may not be reproduced without written permission from the authors of this poster. s2010515 fcpanp 2020 sher_without qr code.indd presented at the 5th fall clinical dermatology conference for pas & nps (fcpanp). background • atopic dermatitis (ad) is a chronic infl ammatory skin disease often associated with atopic comorbidities1 • as previously reported, patients with ad have a high prevalence of comorbid atopic conditions, including allergic rhinitis (ar)2 • dupilumab, a fully human monoclonal antibody, blocks the shared receptor subunit for interleukin (il)-4 and il-13, inhibiting signaling of both il-4 and il-13, which are key drivers of type 2-mediated infl ammation in multiple diseases, such as ad and ar3 • in dupilumab trials, > 80% of adult patients have reported ≥ 1 comorbid condition, and as many as 50% have reported comorbid ar4 dupilumab in adolescents with moderate-to-severe atopic dermatitis and a history of allergic rhinitis: subgroup analysis from a phase 3 trial (liberty ad adol) lawrence sher1, weily soong2, randy prescilla3, zhen chen4, ashish bansal4 1peninsula research associates, rolling hills estates, ca; 2alabama allergy & asthma center, birmingham, al; 3sanofi genzyme, cambridge, ma; 4regeneron pharmaceuticals inc., tarrytown, ny; usa analysis • this analysis includes the subpopulation of patients who reported a history of ar at baseline and the complementary subpopulation without a history of ar • effi cacy outcomes were analyzed among randomized patients (full analysis set) among the 2 subgroups • safety was assessed among patients who received ≥ 1 dose of any study drug results patients • of the 251 patients randomized, 166 had a history of ar and 85 did not have a history of ar • baseline disease characteristics were similar among treatment groups and between subgroups with a history of ar and no history of ar (table 1) objective • to determine if a history of ar impacts the effi cacy of dupilumab treatment in adolescent patients with moderate-to-severe ad enrolled in a phase 3 trial a p ro p o rt io n o f p a ti e n ts a c h ie vi n g ig a 0 o r 1 a t w e e k 1 6 ( % ) placebo 0 n = 28 n = 50 22.0 18.5 (6.06, 30.93) n = 34 11.8 11.8 (0.93, 22.59) dupilumab 300 mg q4w dupilumab 200 mg or 300 mg q2w 0 20 40 60 80 100 patients with ar patients without ar n = 59 25.4 21.9 (9.82, 34.01) n = 23 21.7 21.7 (4.88, 38.60) 3.5 n = 57 b p ro p o rt io n o f p a ti e n ts a c h ie vi n g e a s i7 5 a t w e e k 1 6 ( % ) placebo dupilumab 300 mg q4w n = 59 n = 23 44.1 35.3 (20.65, 49.94) 34.8 27.6 (5.96, 49.32) dupilumab 200 mg or 300 mg q2w 0 20 40 60 80 100 patients with ar patients without ar n = 34 36.0 27.2 (12.03, 42.42) 41.2 34.0 (14.94, 53.13) n = 50 8.8 n = 57 n = 28 7.1 p ro p o rt io n o f p a ti e n ts a c h ie vi n g ≥ 3 -p o in t im p ro ve m e n t in p e a k p ru ri tu s n r s a t w e e k 1 6 ( % ) f placebo dupilumab 300 mg q4w n = 59 n = 23 47.5*** 36.9 (21.90, 51.96) 52.2** 45.0 (22.50, 67.56) dupilumab 200 mg or 300 mg q2w 0 20 40 60 80 100 patients with ar patients without ar n = 34 38.8** 28.2 (12.45, 44.05) 38.2** 31.1 (12.18, 50.01) n = 49 10.5 n = 57 n = 28 7.1 e p ro p o rt io n o f p a ti e n ts a c h ie vi n g ≥ 4 -p o in t im p ro ve m e n t in p e a k p ru ri tu s n r s a t w e e k 1 6 ( % ) placebo 26.5 21.2 (7.48, 34.87) n = 34 26.5 22.9 (6.55, 39.24) dupilumab 300 mg q4w dupilumab 200 mg or 300 mg q2w 0 20 40 60 80 100 patients with ar patients without ar n = 59 37.3 31.9 (18.26, 45.61) n = 23 34.8 31.2 (10.57, 51.85) n = 56 n = 28 3.65.4 n = 49 –27.3 –16.7 d % c h a n g e f ro m b a s e lin e in e a s i a t w e e k 1 6 , l s m e a n ( ± s e ) placebo dupilumab 300 mg q4w dupilumab 200 mg or 300 mg q2w –100 –80 –60 –40 –20 0 n = 23n = 59 –62.5 –45.7 (–70.03, –21.45)–67.8 –40.5 (–55.09, –25.93)–69.6 –52.9 (–74.62, –31.11) –62.2 –35.0 (–50.46, –19.46) n = 34n = 50n = 28n = 57 patients with ar patients without ar p ro p o rt io n o f p a ti e n ts a c h ie vi n g ≥ 6 -p o in t im p ro ve m e n t in c d l q i a t w e e k 1 6 ( % ) h placebo dupilumab 300 mg q4w n = 50 n = 21 60.0** 38.0 (20.22, 55.78) 61.9** 46.5 (21.55, 71.49) dupilumab 200 mg or 300 mg q2w 0 20 40 60 80 100 patients with ar patients without ar n = 28 62.8*** 40.8 (22.34, 59.25) 53.6** 38.2 (15.09, 61.29) n = 43 22.0 n = 50 n = 26 15.4 c p ro p o rt io n o f p a ti e n ts a c h ie vi n g e a s i5 0 a t w e e k 1 6 ( % ) placebo n = 28n = 57 dupilumab 300 mg q4w dupilumab 200 mg or 300 mg q2w 0 20 40 60 80 100 66.1*** 50.3 (34.97, 65.66) n = 23 47.8** 40.7 (18.15, 63.22) 15.8 7.1 52.0*** 36.2 (19.44, 52.98) n = 34 58.8*** 51.7 (32.58, 70.78) n = 50 n = 59 patients with ar patients without ar –20.6 –18.7 g % c h a n g e f ro m b a s e lin e in p e a k p ru ri tu s n r s a t w e e k 1 6 , l s m e a n ( ± s e ) placebo dupilumab 300 mg q4w dupilumab 200 mg or 300 mg q2w –100 –80 –60 –40 –20 0 –47.5*** –26.9 (–39.35, –14.42) –52.0** –33.3 (–52.58, –14.00) –44.4** –23.9 (–37.53, –10.20) –48.9** –30.2 (–50.48, –9.83) patients with ar patients without ar n = 34 n = 59 n = 23n = 57 n = 28 n = 50 figure 2. (a) proportion of patients achieving iga 0 or 1 at week 16; (b) proportion of patients achieving easi-75 at week 16; (c) proportion of patients achieving easi-50 at week 16; (d) percent change from baseline to week 16 in easi; (e) proportion of patients with ≥ 4-point reduction from baseline in peak pruritus nrs at week 16; (f) proportion of patients with ≥ 3-point reduction from baseline in peak pruritus nrs at week 16; (g) percent change from baseline to week 16 in peak pruritus nrs scores; (h) proportion of patients with ≥ 6-point reduction from baseline in cdlqi through week 16. difference vs placebo (95% confi dence interval (ci)) are shown below percent values on top of bar graphs. **p < 0.01; ***p < 0.0001. ls, least squares; se, standard error. screening • age 12–17 years • moderate-to-severe ad • inadequately controlled with topical therapies • scores on iga ≥ 3, easi ≥ 16, peak pruritus nrs ≥ 4; bsa involvement ≥ 10% washout • prior medication stratification • body weight (< 60 kg vs ≥ 60 kg) • iga (3 vs 4) treatment period (16 weeks) follow-up period (12 weeks) loading dose on day 1a day –35 to day –1 baseline week 28week 16 post-treatment options • open-label extension • safety follow-up through week 28 placebo (n = 85) dupilumab q4w 300b mg sc (n = 84) dupilumab q2w 200/300c mg sc (n = 82) r 1:1:1 figure 1. study design. t opical therapy and other systemic ad therapies were prohibited but allowed as rescue treatment for intolerable symptoms. aall patients receiving q4w, regardless of weight, received a 600 mg loading dose. for q2w, patients with body weight < 60 kg at baseline received a loading dose of 400 mg on day 1, while patients with body weight ≥ 60 kg received a 600 mg loading dose. bin the q4w group, patients received 300 mg regardless of body weight. cin the q2w group, patients with body weight < 60 kg received 200 mg of the study drug; patients with body weight ≥ 60 kg received 300 mg. bsa, body surface area; easi, eczema area and severity index; iga, investigator’s global assessment; nrs, numerical rating scale; q2w, every 2 weeks; q4w, every 4 weeks; r, randomization; sc, subcutaneous. conclusions • similar to previous fi ndings in the adult population,5,6 dupilumab improved signs and symptoms of ad in adolescent patients with moderate-to-severe ad regardless of history of ar, indicating that a potentially increased type 2 burden does not impact dupilumab effi cacy methods study design • this was a randomized, double-blinded, placebo-controlled, parallelgroup, phase 3 trial of dupilumab in adolescents with moderate-to-severe ad (liberty ad adol, nct03054428, figure 1)5 table 1. baseline disease characteristics by history of ar. patients with a history of ar patients without a history of ar placebo (n = 57) dupilumab 300 mg q4w (n = 50) dupilumab 200 mg or 300 mg q2w (n = 59) placebo (n = 28) dupilumab 300 mg q4w (n = 34) dupilumab 200 mg or 300 mg q2w (n = 23) duration of ad, mean (sd), years 12.4 (3.37) 12.2 (3.08) 12.3 (3.06) 12.0 (3.64) 11.6 (3.32) 12.9 (2.76) iga score 4, n (%) 33 (57.9) 28 (56.0) 32 (54.2) 13 (46.4) 18 (52.9) 11 (47.8) easi, mean (sd) 37.3 (14.00) 36.2 (15.05) 35.4 (12.68) 32.0 (13.46) 35.1 (14.68) 34.9 (16.75) scorad total score, mean (sd) 71.8 (13.48) 69.7 (13.27) 71.4 (13.12) 67.7 (12.56) 70.0 (15.49) 68.5 (15.80) bsa involvement of ad, mean (sd), % 58.9 (24.34) 58.1 (22.68) 57.1 (19.99) 51.3 (23.28) 55.2 (24.93) 53.0 (24.91) peak pruritus nrs, mean (sd) 7.6 (1.65) 7.3 (2.06) 7.5 (1.45) 7.9 (1.58) 7.8 (1.44) 7.7 (1.70) cdlqi, mean (sd) 13.1 (6.69) 15.2 (6.97) 12.4 (5.93) 13.2 (6.90) 14.2 (8.00) 14.5 (6.81) cdlqi, children’s dermatology life quality index; scorad, scoring atopic dermatitis; sd, standard deviation. table 2. safety outcomes in adolescent patients. patients with, n (%) placebo (n = 85) dupilumab 300 mg q4w (n = 83) dupilumab 200 mg/300 mg q2w (n = 82) teae 59 (69.4) 53 (63.9) 59 (72.0) teae leading to permanent study discontinuation 1 (1.2) 0 0 serious teae 1 (1.2) 0 0 death 0 0 0 most common teaesa dermatitis atopic (pt) 21 (24.7) 15 (18.1) 15 (18.3) skin infection (adjudicated) 17 (20.0) 11 (13.3) 9 (11.0) upper respiratory tract infection (pt) 15 (17.6) 6 (7.2) 10 (12.2) headache (pt) 9 (10.6) 4 (4.8) 9 (11.0) conjunctivitisb 4 (4.7) 9 (10.8) 8 (9.8) nasopharyngitis (pt) 4 (4.7) 9 (10.8) 3 (3.7) infection and infestation (soc) 37 (43.5) 38 (45.8) 34 (41.5) injection-site reaction (hlt) 3 (3.5) 5 (6.0) 7 (8.5) herpes viral infection (hlt) 3 (3.5) 4 (4.8) 1 (1.2) aby pt, in ≥ 5% of patients in any treatment group. bincludes the pts atopic keratoconjunctivitis, conjunctivitis, conjunctivitis allergic, conjunctivitis bacterial, conjunctivitis viral. hlt, meddra high level term; meddra, medical dictionary for regulatory activities; pt, meddra preferred term; soc, meddra system organ class; teae, treatment-emergent adverse event. references: 1. shrestha s, et al. adv ther. 2017;34:1989-2006. 2. silverberg ji, simpson el. pediatr allergy immunol. 2013;24:476-86. 3. gandhi na, et al. nat rev drug discov. 2016;15:35-50. 4. thaçi et al. j allergy clin immunol. 2018;141 suppl:ab136. data presented at 2018 american academy of allergy, asthma & immunology (aaaai)/world allergy organization (wao) joint congress; orlando, fl, usa; march 2–5, 2018; poster p430. 5. simpson el, et al. jama dermatol. 2019 nov 6 [epub ahead of print]. doi: https://doi.org/10.1001/jamadermatol.2019.3336 6. prens e, et al. allergy. 2018;73(s105): 3-115 ab0140. data presented at 2018 european academy of allergy and clinical immunology (eaaci); munich, germany; may 26–30, 2018; oral presentation and poster. acknowledgments: data fi rst presented at the 2020 annual meeting of the american academy of allergy, asthma & immunology (aaaai); philadelphia, pa, usa; march 13–16, 2020. research sponsored by sanofi and regeneron pharmaceuticals, inc. clinicaltrials.gov identifi er: nct03054428 (liberty ad adol). medical writing/editorial assistance provided by luke shelton, phd, of excerpta medica, funded by sanofi genzyme and regeneron pharmaceuticals, inc. disclosures: sher l: aimmune, optinose, regeneron pharmaceuticals, inc., sanofi genzyme – advisory board member; regeneron pharmaceuticals, inc., sanofi genzyme – speaker fees; aimmune, amgen, astrazeneca, circassia, dbv, galderma, gsk, lupin, merck, mylan, novartis, novo nordisk, optinose, pearl, pfi zer, pulmagen, roxane, sanofi , spirometrix, teva, vectura, watson – clinical trial funding. soong w: astrazeneca, regeneron pharmaceuticals, inc. – speaker, advisory board member, investigator; abbvie, regeneron pharmaceuticals, inc. – consultant; abbvie – investigator; aimmune, gsk, leo pharma, novartis, pfi zer, teva, vanda pharmaceuticals – investigator grants; genentech – investigator grants, honorarium, advisory board member; stallergenes greer – advisory board member. chen z, bansal a: regeneron pharmaceuticals, inc. − employees and shareholders. prescilla r: sanofi genzyme − employee, may hold stock and/or stock options in the company. safety methods (cont.) results (cont.) effi cacy ● atopic dermatitis (ad) is a chronic inflammatory skin disease,1 characterized by eczematous lesions and multiple symptoms including pruritus, sleep disturbance, and depression2,3 ● tralokinumab is a first-in-class, fully human monoclonal antibody, designed to neutralize interleukin-13, a key driver of the underlying inflammation of ad which is overexpressed in lesional and non-lesional ad skin4,5 ● the ecztra 3 study reflected clinical practice by evaluating the use of tralokinumab 300 mg every 2 weeks in combination with a topical corticosteroid (tcs) used as needed on active lesions compared with placebo plus tcs as needed6 ● tralokinumab plus tcs demonstrated superiority versus placebo plus tcs in achieving the primary endpoints of an investigator’s global assessment (iga) score of 0 (clear) or 1 (almost clear) [iga-0/1] and a 75% improvement in eczema area and severity index (easi-75) at week 166 ● use of iga and easi as primary outcomes in clinical studies is driven in part by guidance from regulatory authorities such as the u.s. food and drug administration and the european medicines agency ● patient−clinician discussions around the decision to continue, switch, combine, increase dose, or stop therapy should be based on a more comprehensive assessment of treatment and response7 ● the harmonising outcome measures for eczema (home) initiative suggested that comprehensive assessment of long-term control of ad should include domains of signs, symptoms, quality of life, and a patient global instrument8 patients and study design ● ecztra 3 enrolled adults with a diagnosis of ad for more than 1 year and a recent history of inadequate response to treatment with topical medications (figure 1) ● patients were randomly assigned (2:1) to either subcutaneous tralokinumab 300 mg every other week plus tcs or placebo every other week plus tcs for 16 weeks, after which tralokinumab responders (iga-0/1 and/or easi-75) were re-randomized 1:1 to continuation treatment with tralokinumab 300 mg every other week or every 4 weeks plus tcs for an additional 16 weeks tralokinumab q4w + tcs (n=69) tralokinumab q2w + tcs (n=69) screening continuation treatment clinical response defined as iga-0/1 or easi-75 o�-treatment period safety follow-up 0–6 weeks 32 weeks 46 weeks16 weeks n=253 n=127 the post-hoc analyses focused on pooled data from all patients who were randomized to tralokinumab at the start of the study 2:1 randomization 1:1 re-randomization washout of tcs and other ad medication initial treatment 300 mg q2w after initial loading dose (600 mg) 16-week responders 16-week non-responders 16-week responders 16-week non-responders tralokinumab q2w + tcs (n=95) placebo q2w + tcs (n=41) tralokinumab q2w + tcs (n=79) tralokinumab q2w + tcs placebo q2w + tcs figure 1. ecztra 3 trial design (nct03363854)6 p a ti e n ts a ch ie vi n g t a rg e t, % 100 10 20 30 50 40 60 70 80 90 0 all patients 204/252 pgi-b + any other target at week 12 175/193 all patients 174/252 pgi-b + any other target at week 12 148/193 easi-50 at week 24 easi-75 at week 24 81% 91% 69% 77% figure 3. impact of holistic assessment of response at month 3 on achievement of easi improvement with tralokinumab q2w or q4w plus tcs at month 6 disease domain and scoring initial treatment phase minimal target (clinically relevant change versus baseline after 3 months) maintenance treatment phase ideal target (mild disease activity after 6 months) table 1. disease domains and targets assessed aweekly average of worst daily score, 11-point scale, 0 = “no itch” to 10 = “worst itch imaginable”; bworst score recorded during the week, 5-point scale, 0 = “not at all” to 4 = “very much”; c10 items addressing impact of skin disease over the last week, 4-point scale, 0 = “not at all, not relevant” to 3 = “very much”; dmeasured at week 20; etotal frequency of 7 symptoms over the last week (itching, sleep, bleeding, weeping, cracking, flaking, and dryness), 5-point scale, 0 = “no days” to 4 = “every day” week 16, n (%) placebo q2w + tcs (n=126) tralokinumab q2w + tcs (n=252) table 3. adverse events in the initial treatment period up to week 16 ae, adverse event, apreferred terms according to medical dictionary for regulatory activities, version 20.0. tralokinumab q2w + tcs (n=253d) aincludes usa and canada; bincludes belgium, germany, netherlands, poland, spain, and uk; cpgi-b: 0: “not at all”, 1: “slightly”, 2: “somewhat”, 3: “a lot”, or 4: “very much”; done patient was not dosed due to use of prohibited medication and was therefore excluded from the full analysis set. tralokinumab improves clinically relevant outcome measures: a post hoc analysis of ecztra 3, a randomized clinical trial in patients with moderate-to-severe atopic dermatitis 1stephan weidinger,1 andrew e. pink,2 juan francisco silvestre,3 azra kurbasic,4 christina kurre olsen,4 andreas westh vilsbøll,4 marjolein de bruin weller5 1department of dermatology and allergy, university hospital schleswig-holstein, kiel, germany; 2st. john’s institute of dermatology, guy’s and st. thomas’ hospitals, london, uk; 3dermatology department, hospital general universitario de alicante, alicante, spain; 4leo pharma a/s, ballerup, denmark; 5department of dermatology and allergology, university medical center utrecht, national expertise center for eczema, utrecht, the netherlands patient characteristics ● patients had a long duration of ad prior to being enrolled into the study; almost half of patients had severe ad (iga-4) at baseline and mean body surface area (bsa) involvement was close to 50% (table 2) ● overall, 60% of patients had a worst pgi-b score of 4 (very much bothered by their ad) at baseline ● ecztra 3 included assessment of: iga and easi assessed every 2 weeks patient global impression of bother (pgi-b) and numerical rating scale (nrs) for worst daily pruritus assessed daily and recorded as the worst weekly and daily score respectively dermatology life quality index (dlqi) and patient-oriented eczema measure (poem) assessed bi-weekly until week 8, every 4 weeks until week 20, and then at week 28 and 32 post hoc analysis ● following home recommendations,8 outcomes were selected in the domains o clinician-assessed signs (easi), patient-reported symptoms (pruritus nrs and poem) quality of life (dlqi), and a patient global instrument (pgi-b) (table 1) ● outcomes were assessed at time points typically used in clinical practice for patient follow-up, i.e. after 3 months in the initiation phase and every 6 months in the maintenance phase ● clinically relevant targets were selected to reflect the achievement of a clinically meaningful change versus baseline during the initial treatment phase (minimal target) and to reflect achievement of mild disease activity (ideal target) during the maintenance phase ameasured at week 20. pruritus nrs assessed in patients with worst daily pruritus nrs 3 at baseline; dlqi and poem assessed in patients with dlqi/poem total score 4 at baseline; pgi-b assessed in patients with pgi-b 1 at baseline. introduction results methods objective ● the objective of this post hoc analysis was to assess response to tralokinumab in combination with tcs as needed, based on outcome domains and time points typically used in clinical practice 2020 fall clinical dermatology conference, october 29-november 1, 2020, live virtual meeting ● this post hoc analysis included pooled data from all patients who were randomized to tralokinumab plus tcs at the start of ecztra 3 to assess: the proportion of tralokinumab plus tcs-treated patients who achieved the individual disease domain targets at 3 and 6 months the impact of selecting patients by holistic assessment at month 3 on the proportion achieving meaningful improvement in the extent and severity of lesions (easi-50 or easi-75) at month 6 • subgroup analyses of patients achieving both a perceived improvement in the overall disease burden (pgi-b) and a meaningful improvement in any one of the other targets at 3 months statistical analyses ● post hoc analysis was based on the full analysis set and included all patients who received tralokinumab plus tcs in the initial treatment period ● in the assessment of the defined binary targets, subjects who received rescue medication were considered non-responders and subjects with missing data were imputed as non-responders table 2. patient demographics and disease characteristics at baseline easi-50 79% (199/252) worst pgi-b �1-point reduction 79% (199/252) dlqi �4 point reduction 77% (191/248) poem �4-point reduction 78% (195/250) worst pruritus nrs �3 point reduction 59% (148/251) patients achieving any of the five defined minimum initiation phase targets after 3 months = 91% (225/247) a b 0% 20% 40% 80% 100% easi �7 69% (147/252) worst pgi-b absolute score �2 43% (108/252) dlqi absolute score �5a 59% (146/248) poem absolute score �7a 37% (93/250) worst pruritus nrs absolute score �4 61% (152/251) patients achieving any of the five defined optimal maintenance phase targets after 6 months = 82% (202/247) 60% 0% 20% 40% 80% 100% 60% figure 2. proportion of patients achieving the individual disease domain targets for (a) clinically relevant change at 3 months and (b) mild ad activity at 6 monthsa safety ● tralokinumab in combination with tcs was well tolerated with the overall safety being comparable to that of placebo in the initial treatment period up to 16 weeks (table 3). overall, the safety profile at week 32 was comparable with the initial treatment period ● tralokinumab in combination with tcs was associated with lower rates of severe and serious infections and eczema herpeticum versus placebo plus tcs ● all conjunctivitis cases were mild to moderate and only one led to treatment discontinuation ● overall, 82% of patients receiving tralokinumab every 2 weeks or every 4 weeks plus tcs achieved at least one of the defined optimal targets (equivalent to mild disease) at month 6 in the maintenance treatment phase (figure 2b) 59−69% achieved mild ad as judged by easi, dlqi, and worst daily pruritus nrs 37% and 43% of patients achieved mild ad as judged by poem or worst weekly pgi-b, respectively ● overall, 78% (193/247 patients with data at baseline and month 3) achieved both a 1-point reduction in pgi-b and at least one of the other disease domain endpoints at month 3 ● response rates for easi-50 and easi-75 at month 6 were higher in the subgroup of patients who achieved both a 1-point reduction in pgi-b and at least one of the other disease domain endpoints at month 3, compared with the whole cohort (figure 3) conclusions ● tralokinumab 300 mg every other week in combination with tcs as needed was associated with a high proportion of patients (91%) achieving a clinically meaningful improvement (minimal target) in at least one of the pre-defined disease domains (ad signs and symptoms and ad-related quality of life) 3 months after initiating treatment ● a high proportion of patients (82%) achieved an outcome equivalent to mild disease activity (ideal target) in at least one of the pre-defined disease domains (ad signs and symptoms and ad-related quality of life) during the maintenance treatment phase ● using a holistic approach combining the achievement of the patients’ impression of burden target (pgi-b) in combination with one other initiation period target increased the proportion of patients who achieved easi-50 and easi-75 in the maintenance period ● this post hoc assessment is in line with previous data showing that iga and easi scores do not correlate perfectly with symptom outcome measures and suggest that jointly agreed treatment targets between patients and the clinician are important, as are holistic assessments references 1. weidinger s, novak n. lancet 2016; 387: 1109–1122. 2. silverberg ji et al. ann allergy asthma immunol 2018; 121: 340–347. 3. dalgard fj et al. j invest dermatol 2015; 135: 984–991. 4. bieber t. allergy 2020; 75: 54–62. 5. tsoi lc et al. j invest dermatol 2019; 139: 1480–1489. 6. weidinger s et al. oral presentation at the american academy of dermatology virtual meeting, 2020. 7. thyssen jp et al. j eur acad dermatol venereol 2020; doi: 10.1111/jdv.16716. 8. chalmers jr et al. br j dermatol 2018; 178: e332–e341. disclosures stephan weidinger has acted as an advisory board member/speaker/investigator for, and/or has received grants/research funding from, abbvie, almirall, laboratorie pharmaceutique, la roche-posay, leo pharma, lilly, novartis, pfizer, sanofi genzyme, and sanofi/regeneron. andrew e. pink has acted as an adviser or speaker for abbvie, almirall, janssen, la roche-posay, leo pharma, lilly, novartis, pfizer, sanofi, and ucb. juan francisco silvestre has acted as a consultant/advisor for abbvie, novartis regeneron, and sanofi genzyme. azra kurbasic, christina kurre olsen, and andreas westh vilsbøll are employees of leo pharma. marjolein de bruin weller has acted as a consultant/advisor for abbvie, leo pharma, lilly, pfizer, regeneron, sanofi genzyme, and ucb, and has received grant/research support from regeneron and sanofi genzyme. the tralokinumab ecztra 3 study was sponsored by leo pharma target achievement at months 3 and 6 ● overall, 91% of patients receiving tralokinumab every 2 weeks plus tcs achieved at least one of the defined minimum targets (clinically relevant change) for easi, pruritus, poem, dlqi, and pgi-b at 3 months (figure 2a) 77-79% achieved a clinically relevant change as judged by easi, pgi-b dlqi, and poem, respectively 59% achieved a clinically relevant change as judged by worst daily pruritus nrs kim papp, md, phd,1 jacek c. szepietowski, md, phd,2 leon kircik, md,3 darryl toth, md,4 michael e. kuligowski, md, phd, mba,5 may e. venturanza, md,5 kang sun, phd,5 eric l. simpson, md6 background ● atopic dermatitis (ad) is a chronic, inflammatory skin disease that greatly impacts patients’ quality of life1,2 ● janus kinases (jaks) modulate inflammatory cytokines involved in the pathogenesis of ad3 and may also directly modulate itch4 ● ruxolitinib (rux) is a potent, selective inhibitor of jak1 and jak25 ● in a phase 2 study (nct03011892), rux cream provided strength-dependent efficacy in patients with ad and a safety profile similar to vehicle6 objectives ● to report efficacy and safety of rux cream in patients with ad in two phase 3 studies (true-ad1 [nct03745638] and true-ad2 [nct03745651]) methods patients and study design ● eligible patients were aged ≥12 years with ad for ≥2 years, an investigator’s global assessment (iga) score of 2 or 3, and 3% to 20% affected body surface area ● key exclusion criteria were unstable course of ad, other types of eczema, immunocompromised status, use of ad systemic therapies during the washout period and during the study, use of ad topical therapies (except bland emollients) during the washout period and during the study, and any serious illness/medical condition that could interfere with study conduct, interpretation of data, or patients’ well-being ● true-ad1 and true-ad2 had identical study designs (figure 1) – in both studies, patients were randomized (2:2:1) to either of 2 rux cream strength regimens (0.75% twice daily [bid], 1.5% bid) or vehicle cream for 8 weeks of double-blind treatment – patients on rux cream could subsequently continue treatment for 44 weeks; patients initially randomized to vehicle were re-randomized 1:1 to either rux cream regimen figure 1. study design vehicle-controlled period (8 continuous weeks) long-term safety (treat as needed for 44 weeks) recurrence of lesions clearance of lesions patients initially randomized to rux remain on their regimen patients on vehicle randomized 1:1 to 0.75% rux or 1.5% rux 1.5% rux bid (n=~240 in each study) 0.75% rux bid (n=~240 in each study) patients randomized 2:2:1 vehicle (n=~120 in each study) rux* visits every 4 weeks week 52day 1 week 8 ad, atopic dermatitis; bid, twice daily; bsa, body surface area; rux, ruxolitinib. * patients will self-evaluate recurrence of lesions between study visits and will treat lesions with active ad (≤20% bsa). if lesions clear between study visits, patients will stop treatment 3 days after lesion disappearance. if new lesions are extensive or appear in new areas, patients will contact the investigator to determine if an additional visit is needed. assessments ● the primary endpoint was the proportion of patients achieving iga-treatment success (iga-ts; score of 0/1 with ≥2-grade improvement from baseline) at week 8 ● the main secondary endpoints were the proportion of patients achieving ≥75% improvement in eczema area and severity index score vs baseline (easi-75) and the proportion of patients with a ≥4-point improvement in itch numerical rating scale (nrs) score from baseline to week 8 statistical analyses ● the primary and main secondary endpoints were analyzed by logistic regression using the intent-to-treat population ● all other secondary endpoints were analyzed using descriptive statistics ● the efficacy population consisted of 631 patients for true-ad1 (all randomized patients) and 577 patients for true-ad2 (vehicle, n=118; 0.75% rux, n=231; 1.5% rux, n=228) ● all patients who applied the study cream at least once (same as all randomized patients) were included in the safety population in both studies 1k. papp clinical research and probity medical research, waterloo, on, canada; 2department of dermatology, venereology and allergology, wroclaw medical university, wroclaw, poland; 3icahn school of medicine at mount sinai, new york, ny, usa; 4xlr8 medical research and probity medical research, windsor, on, canada; 5incyte corporation, wilmington, de, usa; 6oregon health and science university, portland, or, usa presented at the fall clinical dermatology conference october 29 – november 1, 2020 results patients ● in true-ad1, 631 patients were randomized, and 558 (88.4%) completed treatment in the 8-week vehicle-controlled period ● in true-ad2, 618 patients were randomized, and 561 (90.8%) completed treatment in the 8-week vehicle-controlled period ● distribution of baseline demographics and clinical characteristics was similar across treatment groups (table 1) table 1. patient demographics and baseline clinical characteristics true-ad1 true-ad2 vehicle (n=126) 0.75% rux (n=252) 1.5% rux (n=253) vehicle (n=124) 0.75% rux (n=248) 1.5% rux (n=246) age, median (range), y 31.5 (12–82) 34.0 (12–85) 30.0 (12–77) 37.5 (12–82) 33.0 (12–81) 32.0 (12–85) 12–17, n (%) 23 (18.3) 53 (21.0) 47 (18.6) 22 (17.7) 55 (22.2) 45 (18.3) ≥18, n (%) 103 (81.7) 199 (79.0) 206 (81.4) 102 (82.3) 193 (77.8) 201 (81.7) female, n (%) 79 (62.7) 154 (61.1) 158 (62.5) 80 (64.5) 150 (60.5) 150 (61.0) race, n (%)* white 85 (67.5) 171 (67.9) 175 (69.2) 84 (67.7) 174 (70.2) 178 (72.4) black 29 (23.0) 55 (21.8) 56 (22.1) 32 (25.8) 63 (25.4) 57 (23.2) other 12 (9.5) 26 (10.3) 21 (8.3) 8 (6.5) 11 (4.4) 11 (4.5) region, n (%) north america 88 (69.8) 176 (69.8) 176 (69.6) 84 (67.7) 166 (66.9) 165 (67.1) europe 38 (30.2) 76 (30.2) 77 (30.4) 40 (32.3) 82 (33.1) 81 (32.9) bsa, mean ± sd, % 9.2±5.1 9.9±5.4 9.3±5.2 10.1±5.8 10.1±5.3 9.9±5.4 baseline easi, mean ± sd 7.4±4.3 8.2±4.8 7.9±4.6 8.2±5.2 8.1±5.0 7.8±4.9 baseline iga, n (%) 2 31 (24.6) 61 (24.2) 60 (23.7) 33 (26.6) 64 (25.8) 63 (25.6) 3 95 (75.4) 191 (75.8) 193 (76.3) 91 (73.4) 184 (74.2) 183 (74.4) itch nrs score, mean ± sd 5.1±2.5 5.1±2.3 5.2±2.5 5.1±2.4 5.2±2.5 4.9±2.5 itch nrs score ≥4, n (%) 78 (61.9) 156 (61.9) 161 (63.6) 81 (65.3) 168 (67.7) 154 (62.6) duration of disease, median (range), y 17.9 (1.9–79.1) 14.1 (1.0–68.8) 16.0 (0–69.2) 15.9 (0.8–70.7) 15.9 (0.1–68.6) 16.6 (0–68.8) facial involvement, n (%) 52 (41.3) 112 (44.4) 118 (46.6) 41 (33.1) 83 (33.5) 79 (32.1) bsa, body surface area; easi, eczema area and severity index; iga, investigator’s global assessment; nrs, numerical rating scale; rux, ruxolitinib. * data missing from 1 patient in the 1.5% rux group in true-ad1. efficacy ● significantly more patients treated with rux cream regimens vs vehicle demonstrated iga-ts (primary endpoint); responses were time and strength dependent (figure 2) ● significantly more patients treated with rux cream achieved easi-75 vs vehicle; responses were time and strength dependent (figure 3) ● both strengths of rux cream showed greater improvement in mean percentage change in easi scores vs vehicle; statistical significance was observed at week 2 and later (figure 4) ● significantly greater reductions in itch nrs scores were observed within 12 hours of the first application of rux cream (1.5%; p<0.05; figure 5) vs vehicle ● significantly more patients treated with rux cream demonstrated clinically meaningful reduction in itch (≥4-point improvement in itch nrs) vs vehicle (figure 6) figure 2. proportion of patients with iga-ts pr op or tio n (s e) o f ig a re sp on de rs , % † 0 10 20 30 40 50 60 pr op or tio n (s e) o f ig a re sp on de rs , % † 0 10 20 30 40 50 60 0 2 4 8 week 0 2 4 8 week true-ad1 true-ad2 vehicle (n=118) 0.75% rux (n=231) 1.5% rux (n=228) vehicle (n=126) 0.75% rux (n=252) 1.5% rux (n=253) 27.3 46.6 53.8 *** 25.0 43.4 51.3 *** 22.2 42.5 50.0 *** 17.3 35.5 39.0 *** 3.2 6.3 15.1 4.2 5.9 7.6 iga, investigator’s global assessment; iga-ts, investigator’s global assessment-treatment success; rux, ruxolitinib; se, standard error. *** p<0.0001. † defined as patients achieving an iga score of 0 or 1 with an improvement of ≥2 points from baseline. patients with missing post-baseline values were imputed as nonresponders at weeks 2, 4, and 8. figure 3. proportion of patients achieving easi-75 pr op or tio n (s e) o f ea si -7 5 re sp on de rs , % † 0 10 20 30 40 50 70 60 pr op or tio n (s e) o f ea si -7 5 re sp on de rs , % † 0 10 20 30 40 50 70 60 0 2 4 8 week 0 2 4 8 week true-ad1 true-ad2 vehicle (n=118) 0.75% rux (n=231) 1.5% rux (n=228) vehicle (n=126) 0.75% rux (n=252) 1.5% rux (n=253) 5.6 14.3 24.6 30.2 51.6 56.0 36.0 58.5 62.1 *** *** 4.2 10.2 14.4 25.5 42.0 51.5 31.6 50.4 61.8 *** *** easi-75, ≥75% improvement in eczema area and severity index score from baseline; rux, ruxolitinib; se, standard error. *** p<0.0001. † patients with missing post-baseline values were imputed as nonresponders at weeks 2, 4, and 8. figure 4. easi percentage change from baseline m ea n (9 5% c i) pe rc en ta ge c ha ng e fr om b as el in e in e as i s co re , % –90 –80 –70 –60 –50 –40 –10 0 –20 –30 m ea n (9 5% c i) pe rc en ta ge c ha ng e fr om b as el in e in e as i s co re , % –90 –80 –70 –60 –50 –40 –10 0 –20 –30 0 2 4 8 week 0 2 4 8 week true-ad1 true-ad2 vehicle 0.75% rux 1.5% ruxvehicle 0.75% rux 1.5% rux *** *** *** *** *** *** –16.1 –23.5 –40.5 –51.9 –68.4 –72.2 –56.6 –71.2 –77.2 *** *** *** *** *** *** –13.5 –21.1 –28.9 –45.6 –65.3 –74.8 –49.5 –66.2 –74.7 easi, eczema area and severity index; rux, ruxolitinib. *** p<0.0001. figure 5. change from baseline in daily itch nrs score m ea n ch an ge f ro m b as el in e in d ai ly it ch n rs s co re –3.5 –3.0 –2.5 –2.0 –1.5 0 –0.5 –1.0 m ea n ch an ge f ro m b as el in e in d ai ly it ch n rs s co re b 7 14 21 28 –3.5 –3.0 –2.5 –2.0 –1.5 0 –0.5 –1.0 b 7 14 21 28 study day study day true-ad1 true-ad2 vehicle 0.75% rux 1.5% ruxvehicle 0.75% rux 1.5% rux –3.39 –2.81 –1.03 *** *** * –1.09 –2.89 –2.88 ****** * b, baseline; nrs, numerical rating scale; rux, ruxolitinib. * p<0.05; *** p<0.0001. figure 6. proportion of patients with ≥4-point improvement in itch nrs pr op or tio n (s e) o f itc h nr s re sp on de rs , % † 0 10 20 30 40 50 60 pr op or tio n (s e) o f itc h nr s re sp on de rs , % † 0 10 20 30 40 50 60 0 2 4 8 week 0 2 4 8 week true-ad1 true-ad2 vehicle (n=80) 0.75% rux (n=157) 1.5% rux (n=146) vehicle (n=78) 0.75% rux (n=156) 1.5% rux (n=161) 5.1 11.5 15.4 26.3 38.5 40.4 33.5 51.6 52.2 ** *** 5.0 12.5 16.3 27.4 38.2 42.732.2 45.2 50.7 *** *** nrs, numerical rating scale; rux, ruxolitinib; se, standard error. ** p<0.001; *** p<0.0001. † patients in the analysis had an nrs score ≥4 at baseline. patients with missing post-baseline values were imputed as nonresponders at weeks 2, 4, and 8. safety ● rux cream was well tolerated and not associated with clinically significant application site reactions (table 2) ● all treatment-related treatment-emergent adverse events (teaes) were mild or moderate in severity ● no teaes suggestive of a relationship to bioavailability were observed table 2. treatment-emergent adverse events true-ad1 true-ad2 vehicle (n=126) 0.75% rux (n=252) 1.5% rux (n=253) vehicle (n=124) 0.75% rux (n=248) 1.5% rux (n=246) patients with teae, n (%) 44 (34.9) 74 (29.4) 73 (28.9) 40 (32.3) 73 (29.4) 58 (23.6) patients with treatment-related teae, n (%) 16 (12.7) 15 (6.0) 14 (5.5) 12 (9.7) 8 (3.2) 11 (4.5) most common treatment-related teaes, n (%) application site burning 2 (1.6) 0 2 (0.8) 8 (6.5) 2 (0.8) 2 (0.8) application site pruritus 2 (1.6) 2 (0.8) 0 4 (3.2) 2 (0.8) 0 pruritus 2 (1.6) 2 (0.8) 1 (0.4) 0 0 0 discontinuation due to a teae, n (%) 5 (4.0) 3 (1.2) 3 (1.2) 3 (2.4) 1 (0.4) 0 serious teae, n (%)* 2 (1.6) 1 (0.4) 2 (0.8) 0 3 (1.2) 1 (0.4) rux, ruxolitinib; teae, treatment-emergent adverse event. * no serious teaes were related to rux treatment. conclusions ● ruxolitinib cream showed superior efficacy vs vehicle in iga-ts, easi-75, and ≥4-point reduction in itch nrs score in these two phase 3 studies ● application of ruxolitinib cream brought about rapid (within 12 hours of initiation of therapy), substantial, and sustained reduction in itch ● ruxolitinib cream demonstrated a dual mode of action: antipruritic and anti-inflammatory ● no notable safety findings (either local or systemic) were associated with treatment, including on sensitive skin areas ● the successful outcomes of true-ad1 and true-ad2 support the potential of ruxolitinib cream as an effective and well-tolerated topical treatment for patients with ad disclosures kp has received honoraria or clinical research grants as a consultant, speaker, scientific officer, advisory board member, and/or steering committee member for abbvie, akros, amgen, anacor, arcutis, astellas, bausch health/valeant, baxalta, boehringer ingelheim, bristol-myers squibb, can-fite, celgene, coherus, dermira, dow pharmaceuticals, eli lilly, galderma, genentech, gilead, glaxosmithkline, inflarx, janssen, kyowa hakko kirin, leo pharma, medimmune, meiji seika pharma, merck (msd), merck serono, mitsubishi pharma, moberg pharma, novartis, pfizer, prcl research, regeneron, roche, sanofi-aventis/genzyme, sun pharmaceuticals, takeda, and ucb. jcs has served as an advisor for abbvie, leo pharma, novartis, pierre fabre, menlo therapeutics, and trevi; has received speaker honoraria from abbvie, janssen-cilag, leo pharma, novartis, sanofi-genzyme, sun pharma, and eli lilly; and has received clinical trial funding from abbvie, almirall, amgen, galapagos, holm, incyte, inflarx, janssen-cilag, menlo therapeutica, merck, novartis, pfizer, regeneron, trevi, and ucb. lk has served as an investigator, consultant, or speaker for abbvie, amgen, anaptys, arcutis, dermavant, eli lilly, glenmark, incyte, kamedis, leo pharma, l’oreal, menlo, novartis, ortho dermatologics, pfizer, regeneron, sanofi, sun pharma, and taro. dt has served as an investigator for abbvie, avillion, amgen, arcutis, astellas, astion, boehringer ingelheim, celgene, dermira, ds biopharma, dow pharmaceuticals, eli lilly, f. hoffmann-la roche ltd, galderma, glaxosmithkline, incyte, isotechnika, janssen, leo pharma, merck, novartis, pfizer, regeneron, and ucb biopharma. mek, mev, and ks are employees and shareholders of incyte corporation. els is an investigator for abbvie, eli lilly, galderma, kyowa hakko kirin, leo pharma, merck, pfizer, and regeneron, and is a consultant with honorarium for abbvie, eli lilly, forte bio, galderma, incyte, leo pharma, menlo therapeutics, novartis, pfizer, regeneron, sanofi genzyme, and valeant. acknowledgments support for this study was provided by incyte corporation. medical writing assistance was provided by mayur kapadia, md, an employee of icon plc (north wales, pa, usa), and was funded by incyte corporation. references 1. wei w, et al. j dermatol. 2018;45(2):150-157. 2. silverberg ji, et al. ann allergy asthma immunol. 2018;121(3):340-347. 3. bao l, et al. jakstat. 2013;2(3):e24137. 4. oetjen lk, et al. cell. 2017; 171(1):217-228. 5. quintas-cardama a, et al. blood. 2010;115(15):3109-3117. 6. kim bs, et al. j allergy clin immunol. 2020;145(2):572-582. efficacy and safety of ruxolitinib cream for the treatment of atopic dermatitis: results from two phase 3, randomized, double-blind studies to download a copy of this poster, scan code. skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 425 brief articles reticular erythematous mucinosis: case report and review of literature roxanne rajaii, ms, do1, summer moon, do1, timothy nyckowski, do2, john pui, md1, michael mahon, do1 1beaumont health systems -farmington hills campus, farmington hills, michigan 2medical college of wisconsinmilwaukee, wisconsin reticular erythematous mucinosis (rem) is a disorder of dermal mucin accumulation that has been reported throughout the world. this rarity of the disease prevents many dermatologists from recognizing its hallmark features and treatment options. in the second-largest clinical study to date on rem, the authors diagnosed only 14 patients with rem over a 5 year period, and all of these patients had been referred by primary dermatologists for alternative diagnoses.1 while there is ongoing debate regarding the pathogenesis and clinical associations of rem, our case report highlights some its most salient characteristics. our diagnostic and treatment approach is based on a review of current research, and this report aims to demonstrate a classical presentation of rem and treatment options. a 29-year-old caucasian female presented with a one-year history of an erythematous, mildly pruritic rash localized bilaterally on the breasts. the patient denied any recent infections, constitutional symptoms, or new medications. she noted a long-standing history of smoking and reported exacerbation of skin lesions with sun exposure. the lesion was unresponsive to several previous antifungal and steroid treatments. on examination, the patient had erythematous reticulated plaques on the lateral aspects of bilateral breasts, more prominent on the left (figure 1). there was also slight erythema with scattered papules in the lower sternal region (figure 2). the initial differential diagnosis included irritant and allergic contact dermatitis, tinea corporis, and interstitial granuloma annulare. reticular erythematous mucinosis (rem) is a rare disorder that requires both a clinical and a pathological diagnosis. multiple relevant associations and triggers are known, though exact etiology is unclear. this report aims to demonstrate a classical presentation of rem and available treatment options that have proved efficacious to date. abstract introduction case report skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 426 figure 1: mildly pruritic, erythematous reticulated plaques on the lateral aspects of the breast a 4 mm punch biopsy of the left breast showed a superficial to mid perivascular inflammatory cell infiltrate consisted predominantly of lymphocytes (figure 3a). the collagen fibers within the reticular dermis were widely separated, and an alcian blue stain showed deposition of increased dermal mucin within these spaces (figure 3b). based on the clinical and histopathological results of the skin biopsy, the patient was diagnosed with reticular erythematous mucinosis. after clearance by an ophthalmologist, the patient was started on 200 mg of hydroxychloroquine daily. appropriate sun protection of the affected area, as well as smoking cessation, were thoroughly discussed with the patient. she denied symptoms of common comorbidities with rem such as discoid lupus erythematosus (dle), idiopathic thrombocytopenic purpura (itp), diabetes mellitus, and thyroid disease. she was instructed to follow-up with her primary care physician for further workup of associated conditions and age-appropriate cancer screening. figure 2: slight erythema with scattered papules in the lower sternal region. reticular erythematous mucinosis was initially classified in 1974, though similar clinical and histological descriptions of plaque-like cutaneous mucinosis date back to 1960.2,3,4,5 rem typically affects middleaged females with a female: male ratio of 2:1.5,6 its hallmark features of are erythematous macules and papules that coalesce into a reticulated pattern, favoring the midline chest and mid-back.5, 6,7 the macules and papules may be indurated but lack scale or other surface changes, and may also be less commonly found on the neck, face, upper abdomen, and limbs.1,5,7most patients show no associated clinical symptoms, though 20-30% of patients report pruritus or a slight burning sensation.1,5,6 rem is a subtype of cutaneous mucinoses that often requires histologic assessment for diagnosis, demonstrating an accumulation of dermal-type mucin in the upper and mid dermis, which is predominantly composed of hyaluronic acid and other glycasimoglycans. discussion skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 427 figure 3: a) moderately dense superficial to mid perivascular lymphocytic infiltrate with separation of reticular dermal collagen. (h and e stain, original magnification 100x). b) increased dermal mucin within reticular dermis. (alcian blue stain, original magnification 100x) alcian blue or colloidal iron staining shows this dermal mucin to be prominent around a perivascular and perifollicular lymphocytic infiltrate.5, 7,9 this excessive mucin accumulation leads to marked separation of dermal collagen bundles, which is a hallmark of rem.7 the epidermis is usually unaffected in rem, with only focal spongiosis and lichenoid inflammation when the epidermis is involved.2,6,7,9 in the 2 largest clinical reports on rem in publication, 20% and 54% of patients reported photosensitivity leading to rem exacerbations.1,5 only 1 of these patients from both studies showed clinically reproducible rem lesions following uva and uvb photo-provocation tests, though smaller studies have demonstrated histological (without clinical) rem exacerbation with photo-provocation.12among reports of rem exacerbated with photo-provocation testing, some patients required up to a 4 week interval to display rem symptoms after testing, making it difficult to demonstrate a causal link between photosensitivity and rem.11,13 smoking appears to be another important risk factor associated with rem, as studies have shown up to 91% concurrence rate.1,10 rem can be comorbid with several medical conditions, including thyroid disease and internal malignancies of the lung, breast, and colon.1,5 less substantiated associations with rem include oral contraceptives, itp, dle, diabetes mellitus, hypertension, hiv, and monoclonal gammopathy.5,7,11,14 currently, hypotheses regarding rem pathophysiology are centered around mucin synthesis, which is modulated by tgf-β, interleukins, tnf-α, and interferons.6 this theory is supported by the association of rem with lung, breast, and colon carcinomas, as mucinogens are produced in these cancerous states and can reach the cutaneous lymphovascular structures as seen on histology.6,7 furthermore, mucinproducing mucin1 and mucin4 genes are upregulated in lung carcinomas.7 dermal fibroblasts have an abnormal response to il1β, resulting in excessive hyaluronic acid production and causing the dermal mucin accumulation seen in rem.6,7,9,10 the differential diagnosis for rem includes lupus erythematous tumidus, and there has been considerable debate regarding the relationship and distinction of these two skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 428 entities. there are subtle clinical and histologic differences between these two entities; perhaps the most distinct is the typical midline location and lack of basement membrane thickening in rem.9 jessner’s lymphocytic infiltrate can be nearly impossible to differentiate clinically and histologically when it presents with increased mucin.5 other cutaneous mucinoses to consider include papular mucinosis, acral persistent papular mucinosis, dermatomyositis, degos disease, and granuloma annulare.7 first-line therapy for rem is antimalarials, including hydroxychloroquine and chloroquine diphosphate.1, 2,5,9,15 these drugs can inhibit the release of il-2 from cd4+ t cells and inhibit major histocompatibility complex expression by macrophages.6 most patients found resolution of rem symptoms in 1-2 months following anti-malarial therapy.1,5 patients on these medications should be monitored for side effects such as irreversible ophthalmologic manifestations, gastrointestinal upset, and neurologic symptoms.1,5,6,9,15 in recalcitrant cases of rem, light therapies have shown some efficacy. pulsed dye laser (pdl) therapy reduces the mucin and lymphocytic infiltrate of rem, with a lower rate of recurrence compared to hydroxychloroquine treatment.16 other light therapies with promising results for treatment of rem include uva and uvb phototherapy.2, 14,16 2 case reports have demonstrated partial treatment of rem with uvb therapy with no appreciable adverse side effects.14,17 animal models suggest that uvb decreases hyaluronic acid synthase activity by decreasing expression of the tgfβ receptor and decreasing production of hyaluronic acid synthase mrna from murine papillary dermis.14 uva, particularly uva-1, penetrates deeper into the dermis and has demonstrated efficacy as monotherapy in rem treatment in 2 reported cases.2,16 uva1can induce proteoglycanase in dermal fibroblasts and induce formation of dermal reactive oxygen species, which may degrade hyaluronic acid depositions.2, 18 reticular erythematous mucinosis can be recognized by clinical and histological findings. studies have demonstrated rem to be associated with sun exposure and smoking.1,10 the best studied and first line drugs of choice for rem include hydroxychloroquine and chloroquine.1,2,5,9,15 uva and uvb therapies may also be useful in treating this relapsing disease in recalcitrant cases. conflict of interest disclosures: none. funding: none. corresponding author: timothy nyckowski 6000 university ave. #450 west des moines, ia 50266 email: timothynyckowski@gmail.com references: 1. kreuter a, scola n, tigges c, altmeyer p, gambichler t. clinical features and efficacy of antimalarial treatment for reticular erythematous mucinosis: a case series of 11 patients. arch dermatol. 2011 jun;147(6):710-5. doi: 10.1001/archdermatol.2011.12. pubmed pmid: 21339419. 2. meewes c, henrich a, krieg t, hunzelmann n. treatment of reticular erythematous mucinosis with uv-a1 radiation. arch dermatol. 2004 jun;140(6):660-2. pubmed pmid: 15210454. conclusion mailto:timothynyckowski@gmail.com skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 429 3. braddock sw, davis cs, davis rb. reticular erythematous mucinosis and thrombocytopenic purpura. report of a case and review of the world literature, including plaquelike cutaneous mucinosis. j am acad dermatol. 1988 nov;19(5 pt 1):859-68. review. pubmed pmid: 3056996. 4. steigleder gk, gartmann h, linker u. rem syndrome: reticular erythematous mucinosis (round-cell erythematosis), a new entity? br j dermatol. 1974 aug;91(2):191-9. pubmed pmid: 4472292. 5. rongioletti f, merlo v, riva s, cozzani e, cinotti e, ghigliotti g, parodi a, kanitakis j. reticular erythematous mucinosis: a review of patients' characteristics, associated conditions, therapy and outcome in 25 cases. br j dermatol. 2013 dec;169(6):1207-11. doi: 10.1111/bjd.12577. pubmed pmid: 23937648. 6. kucukunal a, altunay i, demirci gt, sarikaya s, sakiz d. reticular erythematous mucinosis on the midline of the back. cutis. 2014 jun;93(6):2946. pubmed pmid: 24999640. 7. thareja s, paghdal k, lien mh, fenske na. reticular erythematous mucinosis-a review. int j dermatol. 2012 aug;51(8):903-9. doi: 10.1111/j.13654632.2011.05292.x. review. pubmed pmid: 22788804. 8. fernandez-flores a, saeb-lima m. mucin as a diagnostic clue in dermatopathology. j cutan pathol. 2016 nov;43(11):1005-1016. doi: 10.1111/cup.12782. review. pubmed pmid: 27500958. 9. cinotti e, merlo v, kempf w, carli c, kanitakis j, parodi a, rongioletti f. reticular erythematous mucinosis: histopathological and immunohistochemical features of 25 patients compared with 25 cases of lupus erythematosus tumidus. j eur acad dermatol venereol. 2015 apr;29(4):689-97. doi: 10.1111/jdv.12654. pubmed pmid: 25087914. 10. haendchen lc, sabbag ds, furlani wde j, de souza pk, rotta o. reticular erythematous mucinosis. cutis. 2014 mar;93(3):e21-4. pubmed pmid: 24738106. 11. adamski h, le gall f, chevrant-breton j. positive photobiological investigation in reticular erythematous mucinosis syndrome. photodermatol photoimmunol photomed. 2004 oct;20(5):235-8. pubmed pmid: 15379872. 12. mcfadden n, larsen te. reticular erythematous mucinosis and photosensitivity: a case study. photodermatol. 1988 dec;5(6):270-2. pubmed pmid: 3249684. 13. morison wl, shea cr, parrish ja. reticular erythematous mucinosis syndrome. report of two cases. arch dermatol. 1979 nov;115(11):1340-2. pubmed pmid: 507890. 14. miyoshi k, miyajima o, yokogawa m, sano s. favorable response of reticular erythematous mucinosis to ultraviolet b irradiation using a 308-nm excimer lamp. j dermatol. 2010 feb;37(2):1636. doi: 10.1111/j.13468138.2009.00779.x. pubmed pmid: 20175851. 15. lin q, luo dq, liu jh, yang w. hydroxychloroquine-induced reversible hypomnesis in a patient with reticular erythematous mucinosis. ann dermatol. 2012 nov;24(4):490-1. doi: 10.5021/ad.2012.24.4.490. pubmed pmid: 23197926; pubmed central pmcid: pmc3505791. skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 430 16. greve b, raulin c. treating rem syndrome with the pulsed dye laser. lasers surg med. 2001;29(3):248-51. pubmed pmid: 11573227. 17. yamazaki s, katayama i, kurumaji y, yokozeki h, nishioka k. treatment of reticular erythematous mucinosis with a large dose of ultraviolet b radiation and steroid impregnated tape. j dermatol. 1999 feb;26(2):115-8. pubmed pmid: 10091482. 18. amherd-hoekstra a, kerl k, french le, hofbauer gf. reticular erythematous mucinosis in an atypical pattern distribution responds to uva1 phototherapy. j eur acad dermatol venereol. 2014 may;28(5):672-3. doi: 10.1111/jdv.12247. pubmed pmid: 23952909. dermatology professionals, even prior to the coronavirus disease 2019 (covid-19) pandemic, have identified that the use of prolonged ppe (i.e. masks, gloves, and gowns) is associated with high rates of various adverse skin reactions (asrs).1 recently, asrs incidence has been reported to range from 61% to 95% and with current cdc hygiene recommendations regarding hand washing and using a 60%-95% alcohol-based hand rub, it is expected to see skin damage.2,3 characteristics most often include dryness, redness, itching, disease flares, and associated risk factors depending on the type of ppe (table 1). with the size and scope of the current pandemic, the healthcare community is most susceptible to these asrs and are often the ones who first seek treatment. table 1: clinical symptoms following prolonged use of ppe1 synopsis type of ppe used symptom identified n95 mask gown acne • itch • rash • pigmentation • scar/redness at nosebridge • dry skin • wheals increased pore size • peeling nose/runny nose • worsened asthma dry skin • itch • rash • wheals results presentation: 30-year-old female nurse noticed a hand rash following ppe attire (repeated gloves) the rash became erythematous itchy scales with painful blistering and fissuring. prior failed treatments included: variety of over-thecounter ointment and creams utilized for weeks, mometasone and tacrolimus all of which provided no relief. 2-weeks: the patient was given clobetasol for 2 weeks once daily and epiceram, a skin barrier repair emulsion containing ceramides, conjugated linoleic acid, and cholesterol (as a 3:1:1 ratio) in an emollient base, once to twice daily as a stepup therapy. the patient stated improvement in pain, blistering, and fissuring within 2 to 3 days of use. a few days later, the itching and erythema also began to improve. maintenance phase (6months): the patient continues to use skin barrier repair emulsion daily as a preventative measure after each hand wash and reports no further ppe associated skin irritation on her hands and has incorporated lifestyle changes (i.e. chemical free soaps and detergents). step-up therapy with skin barrier repair emulsion in personal protective equipment (ppe) associated adverse skin reactions during the covid-19 pandemic itch • rash katlyn anderson, pa-c arkansas dermatology and skin cancer center, little rock, ar objective epiceram is a skin barrier repair emulsion containing ceramides, conjugated linoleic acid, and cholesterol (as a 3:1:1 ratio) in an emollient base. lipid-based barrier repair therapy, if comprised of the 3 key stratum corneum lipids, in sufficient quantities and at an appropriate molar ratio, may have the potential to correct the barrier abnormality and reduce inflammation in a variety of dermatoses.4 the aim was to identify individual cases of ppe associated asrs in healthcare workers and evaluate the step-up therapy and maintenance use of a lipid based barrier repair therapy. gloves conclusions step-up and maintenance therapy with a 3:1:1 skin barrier repair emulsion was associated with improved outcomes in ppe associated skin irritation on the hands. as covid-19 has enhanced a focus on proper hygiene and ppe, asrs are likely to become more prevalent not only in the healthcare community but at some point will move towards frontline workers, in general. it is therefore important to re-evaluate and evolve approaches in the prevention, treatment, and maintenance of ppe associated asrs. further well controlled analyses are needed to elucidate the findings of this case report. methods this patient case report reviews the signs, symptoms, diagnostic work-up, treatment, and follow up of a 30-year old female nurse working in allergy and asthma. disclosures katlyn anderson is a paid consultant to primus pharmaceuticals. references 1.foo cc, goon a, leow yh, et al. adverse skin reactions to personal protective equipment against severe acute respiratory syndrome – a descriptive study in singapore. contact dermatitis 2006: 55: 291–294 2.hu k, fan j, li x, gou x, li x, zhou x. the adverse skin reactions of health care workers using personal protective equipment for covid-19. medicine 2020;99:24(e20603) 3.centers for disease control and prevention. hand hygiene recommendations guidance for healthcare providers about hand hygiene and covid-19. https://www.cdc.gov/coronavirus/2019-ncov/hcp/hand-hygiene. html. accessed 21 sept 2020 4.elias pm, wakefield js, man m. moisturizers versus current and next-generation barrier repair therapy for the management of atopic dermatitis. skin pharmacol physiol 2019;32:1–7 skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 78 short communications expanding armor-like scales in a middle-aged woman christina e. bax, ba1, robert j. smith, md1, cory l. simpson, md, phd1 1department of dermatology, university of pennsylvania, philadelphia, pa to the editor: a woman in her 50s presented with a 7-month history of worsening pruritic papules and bullae on her face, trunk, arms, and axillae. her medical history was significant for meniere disease and hyperthyroidism. at an outside clinic, an initial skin biopsy from the arm showed intraepidermal acantholysis with dyskeratosis and she was diagnosed with transient acantholytic dermatosis (grover disease). treatments included triamcinolone ointment, doxycycline, antihistamines, and short courses of prednisone without clinical improvement. over the following two months, her eruption worsened, and she developed painful oral mucosal erosions. physical examination revealed vegetative scale-crusts overlying erosions on the face, arms, and chest in an armor-like pattern (figure 1) as well as flaccid bullae on the back and erosions of the gingival and labial mucosae. a shave biopsy of the skin from the upper back was performed (figure 2). direct immunofluorescence showed intercellular epidermal deposition of igg and c3. indirect immunofluorescence was positive on monkey esophagus substrate in an intercellular pattern at a titer of 1:5120 and enzyme-linked immunosorbent assay (elisa) quantified anti-desmoglein-1 (dsg1) and anti-desmoglein-3 (dsg3) antibodies at 620 (negative<20) and 176 units (negative<20), respectively. figure 1. armor-like vegetative scale-crusts on the right chest and arm. pemphigus vulgaris (pv) is an autoimmune blistering disease that affects stratified epithelia including the skin and mucosal surfaces. pv is characterized by loss of keratinocyte cell-to-cell adhesion secondary to circulating autoantibodies targeting the adhesive domains of desmosomal cadherins, dsg1 and dsg3. binding of autoantibodies compromises tissue integrity, leading to intraepithelial acantholysis, which manifests in patients as bullae and erosions.1 the diagnosis should be considered in patients with flaccid skin bullae, but pv may initially present with only skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 79 mucosal erosions or gingival sloughing. as in this case, vegetative scale-crusts can develop over long-standing erosions and, particularly when they are localized to intertriginous areas, the disease may be termed pemphigus vegetans. figure 2. histopathology shows the characteristic tombstone pattern resulting from suprabasal epidermal acantholysis (h&e x40). scale bar = 100 microns. while a biopsy of grover disease can show pv-like suprabasal acantholysis, mucosal erosions are not seen in this disease. likewise, pemphigus foliaceus (pf) lacks mucosal involvement due to production of anti-dsg1 but not anti-dsg3 autoantibodies1; 2 and presents with more superficial skin erosions and crusting from subcorneal acantholysis. bullous pemphigoid and linear iga bullous dermatosis can feature both oral erosions and skin blistering, but they are more likely to produce larger and tense bullae due to sub-epidermal blister formation. definitive diagnosis of pv depends on demonstration of typical suprabasal epidermal acantholysis along with detection of tissue-deposited or circulating auto-antibodies by immunofluorescence or elisa, which measures antibodies recognizing dsg1 and/or dsg3.2 treatment of pv is dictated by the extent of skin and/or mucosal involvement. limited disease may be managed with high-potency topical corticosteroids while extensive disease necessitates initial high-dose systemic corticosteroids with transition to a steroid-sparing immunosuppressive agent.2 rituximab, an anti-cd20 monoclonal antibody, was approved by the u.s. food and drug administration for moderate-tosevere pv.3 other off-label systemic agents that may be employed include mycophenolate, azathioprine, methotrexate, dapsone, and intravenous immunoglobulin.2 although relapse rates remain high in pv, rituximab can induce long-term remission4 and ongoing clinical trials assessing comparative treatment efficacy should advance evidence-based practices for treating pv patients. conflict of interest disclosures: none funding: c.l.s. is supported by nih k08-ar075846 corresponding author: cory l. simpson, md, phd department of dermatology hospital of the university of pennsylvania 3600 spruce street, 2 east gates building #2063 philadelphia, pa 19104 phone: 215-614-1612 fax: 215-615-3140 email: cory.simpson@pennmedicine.upenn.edu references: 1. mahoney mg, wang z, rothenberger k, koch pj, amagai m, stanley jr. explanations for the clinical and microscopic localization of lesions in pemphigus foliaceus and vulgaris. j clin invest. 1999;103(4):461-468. 2. schmidt e, kasperkiewicz m, joly p. pemphigus. lancet. 2019;394(10201):882-894. 3. joly p, maho-vaillant m, prost-squarcioni c, et al. firstline rituximab combined with short-term prednisone versus prednisone alone for the treatment of pemphigus (ritux 3): a prospective, multicentre, parallel-group, openlabel randomised trial. lancet. 2017;389(10083):20312040. 4. kushner cj, wang s, tovanabutra n, tsai de, werth vp, payne as. factors associated with complete remission after rituximab therapy for pemphigus. jama dermatol. 2019;155(12):1404-1409 mailto:cory.simpson@pennmedicine.upenn.edu skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 308 in-depth reviews revisiting the beneficial effects of estrogen on the skin: a comprehensive review of the literature and a look to the future ryan m. svoboda md, msa, james q. del rosso dob, josh a. zeichner mdc, zoe d. draelos mdd aduke university school of medicine, durham, nc bjdr dermatology research, las vegas, nv cicahn school of medicine at mount sinai, new york, ny ddermatology consulting services, high point, nc medical advances and public health initiatives have led to a 62% increase in mean life expectancy over the course of the last century.1 this significant improvement in lifespan has led to new challenges in addressing physiologic aging processes and treating diseases that are rarely encountered in younger individuals. although all organ systems undergo change with increasing age, the integumentary system—given both its size and its exposure to the external environmental forces—is highly susceptible. as the skin ages, its structure begins to change in predictable ways. processes such as thinning of the epidermis2 and decreased density of collagen and elastin fibers3 lead to perceptible changes in appearance such as atrophy and wrinkling. it is increasingly apparent that hormonal changes play a significant role in this process. observation of increased susceptibility to age-associated changes in the skin of post-menopausal women has led to understanding of the importance of estrogens in the maintenance of integumentary health and appearance.4 introduction the process of aging is associated with anticipated cutaneous changes such as epidermal thinning, dehydration, loss of barrier function, and decreased extracellular matrix components. these physiologic changes translate to clinical findings such as atrophy, pigmentary changes, and wrinkling. over the past century, the role of decreased circulating estrogens in the process of cutaneous aging has been elucidated. estrogen replacement, both systemic and topical, has been shown to have positive effects on aging skin by promoting fibroblast proliferation and increasing collagen density. however, despite these positive effects on skin health and appearance, estrogens also display a wide-range of actions on various other systems. even topical estrogen application can result in unwanted systemic effects. research into alternative substances such as soft estrogens—synthetic, non-hormonal molecules that produce local, cutaneous estrogenic effects and are then metabolized to inactive compounds prior to being absorbed into the systemic circulation— suggests that estrogenic-like benefits on aging skin could be harnessed safely, while avoiding the potential pitfalls associated with estrogen use. abstract skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 309 in this article, we review the historical observations that have led to the current understanding of estrogenic interaction with the skin, we summarize research detailing the positive effects of estrogen on aging skin, and we discuss the controversies related to the use of estrogen-containing compounds for skin rejuvenation. finally, we discuss areas of active investigation aimed at devising novel, non-hormonal synthetic products that locally recapitulate the positive effects of estrogen while avoiding unwanted extracutaneous side effects. anecdotal observations suggesting the importance of estrogens to skin health date back to at least the first decades of the 20th century, when it was commonplace for estrogen-containing products to be marketed as over-the-counter cosmetic facial creams.5 major changes were introduced when the federal food, drug, and cosmetic act of 1938—brought about by concern over instances of injury and death related to use of consumer products—formally defined cosmetic products as those that do not alter structure or function of tissues.6 under this doctrine, creams and ointments containing hormones—formerly mainstay ingredients of over-the-counter products—were reclassified as drugs and placed under the jurisdiction of the fda. with increased regulation, widespread use of estrogen-containing topical products for skin rejuvenation predictably decreased. however, this created an impetus for formal and systematic investigation into the cutaneous effects of estrogens. as early as the 1940s, evidence linking application of topical estrogens to the reversal of agerelated skin changes began to appear in the scientific literature. in an early experiment, goldzieher extrapolated that the beneficial effects of estrogens on genital atrophy in post-menopausal women might apply to the skin more broadly.7 he tested his hypothesis by treating the skin of five post-menopausal women with topical estrogen ointments, containing either estradiol or diethylstilbestrol (a synthetic nonsteroidal estrogen no longer in use due to its effects on the children of women exposed during pregnancy). after six weeks of treatment, biopsies of the treated individuals revealed thickening of the atrophic epidermis and increased hypodermal connective tissue—changes not noted from biopsies of three control individuals treated with a vehicle alone. these results led goldzieher to conclude that application of topical estrogens might be useful for the reversal of age-related pathologic changes. these early findings demonstrating the effects of estrogens on integumentary structure were replicated by eller and eller three years later in a larger group of patients.8 despite these promising early observations in human subjects, work in castrated mice provided contradictory data, with low-dose, short-duration estrogen therapy increasing epidermal thickness and high-dose, longduration therapy paradoxically leading to acceleration of epidermal thinning.9 in 1950, dunaif and finnerty showed that in ovariectomized mice, injections of low doses of estrogen slowed epidermal thinning whereas high-dose injections were associated with an exacerbation of the process, corroborating the earlier findings.10 these same researchers noted that topical application of estrogen resulted in increased epidermal proliferation, although lower topical concentrations produced a more profound positive effect than higher doses. these findings led dunaif and finnerty to hypothesize that estrogens act locally at the historical perspective skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 310 skin to promote epidermal thickening, but that this effect is antagonized when higher systemic concentrations are achieved, possibly due to a secondary mechanism of action at a remote site.10 these early experiments laid the scientific foundation for the treatment of aging skin with estrogens. subsequent work over the past several decades has continued to elucidate the mechanisms by which estrogenic compounds delay and reverse ageassociated atrophy. although not well understood at the time, many of the estrogenic effects on skin noted by these pioneer researchers are now thought to be related to the integumentary system’s function as a peripheral endocrine organ— producing, altering, and responding to hormonal signals. although the primary functions of the skin have traditionally been barrier function, sensation, and temperature regulation, more recent research has begun to delineate the role of hormones (including estrogen) in influencing the structure and function of the skin. additionally, the ability of the skin to manufacture and metabolize hormones has become increasingly apparent.11 these observations have made clear the integument’s role in the endocrine system. the neuroendocrine theory of aging proposes that senescent processes are a result of naturally-occurring changes in the complex signaling network of the hypothalamic-pituitary-adrenal axis.12 resultant deficiencies in the communication between different organs involved in this system lead to structural changes, and in many cases, decreased functionality. decreases in estrogen in particular have been implicated in age-related pathology in a variety of organ systems and appear to have an important impact on multiple components of the skin, as outlined previously.13 the endocrine theory of aging, when considered in the context of the skin, offers an explanation as to why many of the skinrelated changes often associated with aging (reduced elasticity, increased wrinkle formation, atrophy)14 are accelerated after the onset of menopause. estrogen signaling represents a complex, incompletely understood pathway.15 multiple hormone receptors (er-α and er-β), which are differentially expressed in varying tissue types, respond to endocrine signals relayed by circulating estrogens.15 even within the environment of the skin alone, estrogen receptors are expressed in varying proportions by multiple skin cell types, including keratinocytes, fibroblasts, melanocytes, and cells of the epidermal appendages.16 although a detailed explanation is beyond the scope of this review, it is important to understand that the underlying positive effects of exogenous estrogen administration on aged skin are likely related to replacing the endogenous signal that becomes diminished with increasing age (and is accelerated in women with the onset of menopause). the action of estrogenic molecules on their hormone receptors have varied and complex consequences on dna transcription. 16. it is this alteration in gene expression that presumably leads to the observed beneficial effects of estrogen on the skin: increased collagen and elastin concentrations, improved skin thickness, enhanced keratinocyte proliferation, and decreased inflammation (table 1). estrogen, the skin, & the endocrine theory of aging skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 311 table 1. observed beneficial effects of estrogens on the skin. increased extracellular matrix components collagen18-20,22 elastin2 fibrillin2 increased retention of moisture increased hyaluronic acid and mucopolysaccharides3 increased thickness of cutaneous layers epidermis23 dermis24 as the human body ages, the concentration of connective tissue components in the dermis, collagen and elastin, both diminish— a process greatly accelerated by menopause in females.17 decreased collagen leads to loss of firmness and also has potential implications for wound healing, while loss of elastin leads to decreased skin turgor. multiple studies have measured the effects of exogenous estrogen on skin collagen levels. work by brincat et al. in the 1980s demonstrated significantly increased collagen content in the skin of postmenopausal women treated with systemic estrogen/testosterone implants (48% greater than the untreated group, p<0.01)18 and topical estradiol gel (increase in abdominal skin collagen content over 1 year treatment period, <0.001)19. these and other studies also provided evidence that local, topical therapy may be more efficacious in increasing skin collagen levels than systemic therapy.20 this finding mirrors the earlier observations of dunaif and finnerty and provides support for the endocrine theory in the process of cutaneous aging.10 a study by varila et al. measured the effects of topical estradiol treatment once daily for three months on the skin of the lower abdomen in 12 post-menopausal women, with contralateral skin being subjected only to vehicle application. upon follow-up, blisters were induced and hydroxyproline (the principal component of collagen) and procollagen levels from the blister fluid were measured. the treated skin showed a 38% increase in hydroxyproline over the control skin (p=0.012) and also an increase in procollagen (p=0.024). electron microscopy revealed increased density of collagen and elastin fibers.21 similar increases in expression of procollagen, tropoelastin, and fibrillin-1 mrna have been seen in aged skin treated with topical 17β-estradiol.2 more recent investigations have also shown similar results with topical estradiol therapy. in 2017, silva et al. performed a randomized trial comparing the effects of topical estradiol and genistein (a phytoestrogen) on the facial skin of 30 women. biopsy revealed increased levels of type i and type iii collagen compared to pre-treatment in both groups, although the increase in collagen concentration was significantly greater in the group treated with topical estradiol (p<0.001).22 in addition to having a positive effect on extracellular collagen and elastin fibers, estrogenic action leads to increased concentrations of hyaluronic acid and mucopolysaccharides, which promotes skin moisture.3 thin, atrophied skin is a common physiologic change associated with increasing age. the impact of estrogens on delaying and reversing this process is well-documented.3 in 1994, maheux et al. performed the first randomized, double-blind, controlled trial assessing the effects of systemic estrogen effect on extracellular matrix effect on skin thickness skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 312 replacement on skin thickness. after 12 months of treatment, epidermal thickness as measured by ultrasonography—increased significantly compared to baseline in the treatment group (p<0.001) and with no significant change in the control group. likewise, the thickness of the dermis, as measured by skin biopsy, also increased significantly in the treatment group.23 patriarca et al. demonstrated similarly enhanced epidermal and dermal thickness in facial skin treated with topical estradiol in a group of patients on chronic systemic estrogen replacement therapy.24 despite the skin benefits, potential concerns have been raised as well. there has been some conflicting reports regarding a potential association between estrogens and malignant melanoma in women.5 a large case-control study conducted by smith et al. did not provide conclusive evidence of a link between oral contraceptive use or oral estrogen replacement therapy and melanoma incidence.25 another potential concern with the use of estrogenic compounds for the treatment of aging skin relates to topical utilization, which is associated with the development of undesirable facial telangiectasias.5 furthermore, pigmentary changes including melasma are a concern with oral estrogen replacement and have been described with topical use as well.26 perhaps the most publicized concern related to estrogens, however, comes from the women’s health initiative (whi) study. the whi was a large, double-armed randomized trial (estrogen-only and combined estrogenprogestin hormone replacement therapy versus placebo) comprised of 27,000 postmenopausal women, aimed at recapitulating and clarifying earlier epidemiologic findings suggesting a potential benefit of hormone replacement therapy (hrt) in protecting against cardiovascular disease and osteoporosis. 27 the trial was discontinued early due to an unexpected increase in thromboembolic adverse events in both treatment groups, including coronary events, stroke, and venous thromboembolism.28 additionally, an increased incidence of invasive breast cancer was seen in the treatment groups.28 publication of data from the whi and resultant pickup by the press led to a decline in the use of hrt, with the proportion of postmenopausal women maintained on this therapy dropping by a factor of four over a ten-year period.29 however, extrapolation of the findings of the whi to topical application on aging skin is problematic. the whi focused solely on oral hrt (and specifically a formulation containing approximately 10 additional active metabolites beyond 17β estradiol) and did not consider topical use. furthermore, the positive cutaneous effects of estrogen were overlooked altogether in this study.5 more recent examinations of the whi data has revealed several issues with the conclusions.27 in an effort to selectively harness the positive effects of estrogen stimulation while avoiding the negative effects, selective estrogen receptor modulators (serms) were developed (table 2). serms are a therapeutic class of compounds which can act as estrogen receptor agonists in specific tissue types while having anti-estrogenic effects in others.16 this medication class holds the potential to incite an estrogenic effect where needed without unintended increased risk of adverse effects, such as carcinogenesis and coronary vascular potential concerns estrogen alternatives skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 313 disease. although the major goals of serm development have been breast cancer treatment and the prevention of osteoporosis, one study by sumino et al. demonstrated similar increases in skin elasticity in a group of 17 postmenopausal women treated with the serm raloxifene compared to 19 women treated with hrt.30 certainly there is potential for a novel serm with efficacy in prevention and treatment of age-related skin pathology to be developed.30 phytoestrogens—estrogen-like compounds derived from plants—also hold promise in recapitulating the positive effects of estrogens on the skin (table 2). recent research has shown promise in the use of phytoestrogens (both dietary and as contained in cosmeceutical products) to improve age-related skin changes17,31, although the effects may be subpar compared to traditional estrogens.22 additionally, phytoestrogens are considered to be endocrine disruptors and thus may have potential deleterious effects of their own.32 significantly more research into the therapeutic effects and safety profile of phytoestrogens is needed prior to widespread use in the treatment of aging skin. the optimism associated with the use of serms and phytoestrogens for treatment of aging skin lies in the promise of harnessing the powerful skin-protective effects while minimizing the far-reaching endocrine actions of these molecules on other organ systems. however, the ideal situation would be one in which these extracutaneous effects could be predictably avoided all together. the realm of soft drug design is an area of interest that holds potential for creating such a situation. table 2. potential alternatives to estrogen therapy for treatment of aging skin. class pros cons selective estrogen receptor modulators (serms) agonist or antagonist effect on estrogen receptor depending on type of tissue act at multiple sites cutaneous effects understudied phytoestrogens shown to have positive effects on age-related skin changes efficacy may be subpar compared to traditional estrogens considered endocrine disruptors may have farreaching systemic effects soft estrogens predictable metabolism to inactive compounds in the hypodermis no significant systemic absorption activity limited to the skin decreased potential for drug-drug interactions not commercially available the overarching principle behind soft drug design is to optimize therapeutic index by specifically targeting metabolism considerations when synthesizing a new therapeutic agent.33 the goal is to develop a close structural analogue of a known compound that exerts a desired therapeutic action locally near the site of delivery and is soft drug design & soft estrogens skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 314 promptly and predictably metabolized to inactive metabolites prior to becoming systemically distributed. apart from this advantage in toxicity, these soft drugs are outside the purview of the cytochrome p450 system and thus drug-drug interactions are unlikely. by altering the chemical structure of known therapeutic agents in a way that predictably alters metabolism, soft drugs have been developed for a wide variety of applications. for example, the addition of an ester group to active compounds leads to local metabolism by ubiquitously-distributed plasma esterases. this allows for medications to be rendered inactive by esterases after acting locally, prior to significant systemic absorption. .34 currently, several united states patents exist for topical estradiol-16α-carboxylic acid esters and 15αcarboxylic acid esters that act locally as “soft estrogens.”35,36 these compounds are irreversibly metabolized to inactive compounds by esterases in the hypodermis (and plasma), thus allowing for local cutaneous estrogenic effects while avoiding unwanted systemic actions. this has been corroborated in rat models.43 unlike classic estrogens, the activity of the compounds is limited to the skin. as opposed to serms, the selective action of soft estrogens is not related to variable activation of different estrogen receptor subsets, but rather altered metabolism, ensuring only local effects and preventing systemic distribution. although not yet commercially available, these synthetic, non-hormonal products hold great promise in harnessing the “holy grail” of estrogenic benefits on aging skin while sidestepping some of the concerns raised by the use of traditional estrogenic compounds. aging of the skin is a complex, multi-faceted process that has not only cosmetic but also medical and quality of life implications. the process appears to be triggered in part by decreasing levels of circulating estrogens with increasing age. although there is significant evidence supporting the positive effects of topical estrogen replacement to combat age-related skin pathology, risk of systemic absorption and resultant untoward adverse effects limit the utility and practicality of such a strategy. the key to combatting the ill effects of aged skin will lie in developing a product that harnesses the protective local effects of estrogens while avoiding the remote, endocrine-related effects on other organ systems. while serms and phytoestrogens hold some promise in this regard, the concept of applying “soft drug design” to the development of locally-acting compounds with estrogenic activity limited to the cutaneous microenvironment holds perhaps the most promise in safely harnessing the positive cutaneous effects of estrogens while avoiding unwanted systemic activity. to prevent significant morbidity in an aging population, continued research leading to the availability of such products will be paramount. conflict of interest disclosures: dr. svoboda received an honorarium from or-genix therapeutics, inc. for participating in a round table discussion. dr. del rosso reports no conflicts of interest with this article. funding: none. corresponding author: ryan m. svoboda md, ms department of dermatology duke university school of medicine durham, nc rmsvoboda@gmail.com conclusion & future directions mailto:rmsvoboda@gmail.com skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 315 references: 1. ten great public health achievements-united states, 2001-2010. mmwr morbidity and mortality weekly report. 2011;60(19):619623. 2. son ed, lee jy, lee s, et al. topical application of 17beta-estradiol increases extracellular matrix protein synthesis by stimulating tgf-beta signaling in aged human skin in vivo. the journal of investigative dermatology. 2005;124(6):1149-1161. 3. shah mg, maibach hi. estrogen and skin. an overview. american journal of clinical dermatology. 2001;2(3):143-150. 4. wilkinson hn, hardman mj. the role of estrogen in cutaneous ageing and repair. maturitas. 2017;103:60-64. 5. draelos zd. topical and oral estrogens revisited for antiaging purposes. fertility and sterility. 2005;84(2):291-292; discussion 295. 6. administration ufad. how did the federal food, drug, and cosmetic act come about? 2018; https://www.fda.gov/aboutfda/transparen cy/basics/ucm214416.htm. accessed february 9, 2018, 2018. 7. goldzieher ma. the effects of estrogens on the senile skin. journal of gerontology. 1946;1:196-201. 8. eller jj, eller wd. estrogenic ointments; cutaneous effects of topical applications of natural estrogens, with report of 321 biopsies. archives of dermatology and syphilology. 1949;59(4):449-464. 9. bullough hf. epidermal thickness following oestrone injections in the mouse. nature. 1947;159(4029):101. 10. dunaif cb, finerty jc. the effects of estrogen administration upon epidermal proliferation. the journal of investigative dermatology. 1950;15(5):363-371. 11. zouboulis cc. the human skin as a hormone target and an endocrine gland. hormones (athens, greece). 2004;3(1):9-26. 12. toescu ec. neuroendocrine theory of aging. in: gellman md, turner jr, eds. encyclopedia of behavioral medicine. new york, ny: springer new york; 2013:13111315. 13. saville cr, hardman mj. the role of estrogen deficiency in skin aging and wound healing. in: farage ma, miller kw, fugate woods n, maibach hi, eds. skin, mucosa and menopause: management of clinical issues. berlin, heidelberg: springer berlin heidelberg; 2015:71-88. 14. monteleone p, mascagni g, giannini a, genazzani ar, simoncini t. symptoms of menopause global prevalence, physiology and implications. nature reviews endocrinology. 2018. 15. stevenson s, thornton j. effect of estrogens on skin aging and the potential role of serms. clinical interventions in aging. 2007;2(3):283-297. 16. thornton mj. estrogens and aging skin. dermato-endocrinology. 2013;5(2):264-270. 17. irrera n, pizzino g, d'anna r, et al. dietary management of skin health: the role of genistein. nutrients. 2017;9(6). 18. brincat m, moniz cf, studd jw, darby aj, magos a, cooper d. sex hormones and skin collagen content in postmenopausal women. british medical journal (clinical research ed). 1983;287(6402):1337-1338. 19. brincat m, versi e, o'dowd t, et al. skin collagen changes in post-menopausal women receiving oestradiol gel. maturitas. 1987;9(1):1-5. 20. oikarinen a. systemic estrogens have no conclusive beneficial effect on human skin connective tissue. acta obstetricia et gynecologica scandinavica. 2000;79(4):250254. 21. varila e, rantala i, oikarinen a, et al. the effect of topical oestradiol on skin collagen of postmenopausal women. british journal of obstetrics and gynaecology. 1995;102(12):985989. https://www.fda.gov/aboutfda/transparency/basics/ucm214416.htm https://www.fda.gov/aboutfda/transparency/basics/ucm214416.htm skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 316 22. silva la, ferraz carbonel aa, de moraes arb, et al. collagen concentration on the facial skin of postmenopausal women after topical treatment with estradiol and genistein: a randomized double-blind controlled trial. gynecological endocrinology : the official journal of the international society of gynecological endocrinology. 2017;33(11):845-848. 23. maheux r, naud f, rioux m, et al. a randomized, double-blind, placebo-controlled study on the effect of conjugated estrogens on skin thickness. american journal of obstetrics and gynecology. 1994;170(2):642-649. 24. patriarca mt, goldman kz, dos santos jm, et al. effects of topical estradiol on the facial skin collagen of postmenopausal women under oral hormone therapy: a pilot study. european journal of obstetrics, gynecology, and reproductive biology. 2007;130(2):202-205. 25. smith ma, fine ja, barnhill rl, berwick m. hormonal and reproductive influences and risk of melanoma in women. international journal of epidemiology. 1998;27(5):751-757. 26. snyder a, schiechert ra, zaiac mn. melasma associated with topical estrogen cream. the journal of clinical and aesthetic dermatology. 2017;10(2):57-58. 27. langer rd, manson je, allison ma. have we come full circle or moved forward? the women's health initiative 10 years on. climacteric : the journal of the international menopause society. 2012;15(3):206-212. 28. rossouw je, anderson gl, prentice rl, et al. risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the women's health initiative randomized controlled trial. jama. 2002;288(3):321-333. 29. sprague bl, trentham-dietz a, cronin ka. a sustained decline in postmenopausal hormone use: results from the national health and nutrition examination survey, 1999-2010. obstetrics and gynecology. 2012;120(3):595603. 30. verdier-sévrain s. effect of estrogens on skin aging and the potential role of selective estrogen receptor modulators. climacteric : the journal of the international menopause society. 2007;10(4):289-297. 31. amori p, lotti j, lotti t, vitiello g. spontaneous retrospective clinical evaluation of a new phytoestrogen-based cosmetic gel cream on postmenopausal women's skin. journal of biological regulators and homeostatic agents. 2017;31(2 suppl. 2):147151. 32. bennetau-pelissero c. risks and benefits of phytoestrogens: where are we now? current opinion in clinical nutrition and metabolic care. 2016;19(6):477-483. 33. bodor n, buchwald p. soft drug design: general principles and recent applications. medicinal research reviews. 2000;20(1):58101. 34. graffner-nordberg m, sjodin k, tunek a, hallberg a. synthesis and enzymatic hydrolysis of esters, constituting simple models of soft drugs. chemical & pharmaceutical bulletin. 1998;46(4):591-601. 35. hochberg rb. estradiol-16α-carboxylic acid esters as locally active estrogens. in: google patents; 2002. 36. hochberg r. 15α-substituted estradiol carboxylic acid esters as locally active estrogens. in: google patents; 2006. skin may 2019 volume 3 issue 3 copyright 2018 the national society for cutaneous medicine 232 compelling comments the rose of dermatology tyler marion, bs, mba1, jake a gibbons, bs1 1university of texas medical branch school of medicine, galveston, tx women serve a pivotal role in dermatology, accounting for more than half of residency spots as of 2015.1 in the early 1900’s, however, women were a minority within the field. the emergence of female dermatologists began with rose hirschler. born in butler, indiana in 1875, hirschler’s journey into dermatology was a circuitous one. she trained to become a certified masseuse in sweden before enrolling at the women’s medical college in philadelphia, graduating with her medical degree in three years.2 after graduation, hirschler worked with renowned dermatologist, jay f. schamberg. schamberg was an important mentor for hirschler. together, they published several papers on various dermatologic conditions including lichen planus, lichen sclerosus, and syphilis.3 hirschler began teaching at women’s medical college of pennsylvania in 1900. she originally served as a gynecology instructor, but her passion for dermatology was not lost. in 1918, she became acting clinical professor of dermatology. obtaining this position was a momentous step forward for women, as this was one of the earliest instances of women teaching women in dermatology.3 in 1936, hirschler took another leap when she was appointed as chair of the department of dermatology, becoming the first female to do so.3 additionally, dr. hirschler was the only female to contribute in the founding of the american academy of dermatology. hirschler’s leadership was unprecedented, and the department of dermatology at women’s medical college flourished under her leadership. unfortunately, her tenure as chair was cut short as she fell victim to lymphocytic leukemia and passed away in 1940.3 to honor dr. hirschler, an award of her namesake, the rose hirschler award, is given annually to female dermatologists who have made significant contributions to medicine and dermatology. dr. hirschler was a true pioneer for women in dermatology, paving the way for future females entering the field. conflict of interest disclosures: none. funding: none. corresponding author: tyler marion, b.s., m.b.a. the university of texas medical branch galveston, tx trmarion9@gmail.com references: 1. grant-kels j, murrell d. history of women in dermatology series. international journal of womens dermatology. 2015;1(3):115. doi:10.1016/j.ijwd.2015.07.005. 2. crissey jt, parish lc, holubar k. historical atlas of dermatology and mailto:trmarion9@gmail.com skin may 2019 volume 3 issue 3 copyright 2018 the national society for cutaneous medicine 233 dermatologists. boca raton: parthenon pub. group; 2002. 3. reid ee, james wd. int j womens dermatol. 2015 apr 23;1(2):99-103. doi: 10.1016/j.ijwd.2015.03.003. references 1. migden mr et al. cancer treat rev. 2018;64:1–10. 2. lear jt et al. br j cancer. 2014;111:1476–1481. 3. kudchadkar r et al. semin oncol. 2012;39:139–144. 4. american cancer society. treating basal cell carcinoma; 2019. available at: https://www.cancer.org/cancer/ basal-and-squamous-cell-skin-cancer/treating/basal-cell-carcinoma.html. [accessed july 24, 2020]. 5. trakatelli m et al. eur j dermatol. 2014;24:312–329. 6. national comprehensive cancer network. nccn clinical practice guidelines in oncology: basal cell skin cancer version 1.2020; 2019. available at: https://www.nccn.org/professionals/physician_gls/pdf/nmsc.pdf. [accessed june 2, 2020]. 7. cancer council australia/australian cancer network. basal cell carcinoma, squamous cell carcinoma (and related lesions) – a guide to clinical management in australia; 2008; 2008. available at: https://www.cancer.org. au/content/pdf/healthprofessionals/clinicalguidelines/basal_cell_carcinoma_squamous_cell_carcinoma_guide_ nov_2008-final_with_corrigendums.pdf. [accessed july 24, 2020]. 8. goldenberg g et al. j am acad dermatol. 2016;75:957–966. 9. sekulic a et al. j am acad dermatol. 2015;72:1021–1026 e1028. 10. basset-seguin n et al. eur j cancer. 2017;86:334–348. acknowledgments the study was funded by regeneron pharmaceuticals, inc. and sanofi. editorial writing support was provided by atif riaz, phd, of prime, knutsford, uk, funded by regeneron pharmaceuticals, inc. and sanofi. disclosures jessica j jalbert, chieh-i chen, ning wu, matthew g fury, and wenzhen ge are employees and shareholders of regeneron pharmaceuticals, inc. emily ruiz has received consulting fees from pellepharm, sanofi, regeneron pharmaceuticals, inc., and leo pharmaceuticals, and is on the consulting and advisory board for checkpoint therapeutics. summary and conclusion • the majority (>99%) of patients initiated vismodegib. • most patients (~70%) used hhis alone versus using hhis as potential neoadjuvant or adjuvant treatment. • although variability was observed based on the selected grace period, median treatment duration was <180 days even when using a 120-day grace period. median duration of hhi treatment was considerably shorter than the median treatment duration (8.6–13.3 months) reported in the pivotal clinical trials of vismodegib.8,9 median duration of use was shorter (by >20 days) for patients using hhis as potential neoadjuvant or adjuvant treatment compared to patients using hhi monotherapy. • few patients reinitiated hhis after discontinuation. the probability of hhi reinitiation within 12 months of discontinuation was 20% using a grace period of 60 days. the probability of reinitiation at 12 months was similar among patients using hhis only and those taking hhis potentially neoadjuvantly. • characterizing real-world persistence on hhis is challenging due to the likely use of drug holidays, as treatment discontinuations, treatment duration, and reinitiations were sensitive to the duration of the grace period selected. moreover, results were sensitive to the type of hhi use (i.e. potential adjuvant or neoadjuvant treatment). • real-world studies of medications with tolerability issues should consider use of drug holidays, and in oncology, the intent of treatment (i.e. adjuvant/ neoadjuvant) use should be considered when characterizing drug exposure. synopsis • in the us, it is estimated that >2 million patients are diagnosed with basal cell carcinoma (bcc) annually.1 • most cases of bcc are treatable by surgery; however, in approximately 1% of patients who develop advanced bcc (including metastatic and locally advanced bcc) additional therapies are required.1-8 • oral targeted therapies such as the hedgehog inhibitors (hhis) vismodegib and sonidegib have shown clinical benefit in advanced bcc.8,9 however, patients treated with hhis commonly experience side effects, which may require permanent or temporary treatment discontinuation.9,10 • we hypothesized that hhi treatment patterns may vary according to the selected grace period. objective • to assess the impact of grace period selection on patterns of hhi treatment discontinuation, treatment duration, and reinitiations among patients with bcc. methods • this retrospective, observational cohort study used data from the ibm marketscan® commercial and medicare claims database. • we identified new users of hhis (vismodegib or sonidegib) by selecting the first hhi dispensation (date of first dispensation = index date) during the study period (january 1, 2013 and march 30, 2019) and requiring ≥6 months of continuous health plan enrollment with medical and pharmacy benefits (i.e. baseline period). to be included in the study, patients were also required to be ≥18 years on the index date and to have ≥1 diagnosis of bcc during the baseline period (including the index date). • hhi use was identified using national drug codes, and bcc diagnoses were identified using international classification of diseases (icd)-9 and icd-10 codes. • hhi use was categorized according to whether it was hhi only, potentially adjuvant, neoadjuvant, or both neoadjuvant and adjuvant use: hhi only: no surgery or radiotherapy within 60 days before or after initiation of hhis potential adjuvant: surgery or radiotherapy followed by initiation of hhis within 60 days potential neoadjuvant: initiation of hhis followed by surgery and radiotherapy within 60 days both: surgery or radiotherapy both within 60 days before and after hhi initiation. • surgery and radiotherapy were identified using icd-9 and icd-10 procedure codes, current procedural terminology, 4th edition codes, or healthcare common procedure coding system codes. • hhi treatment discontinuations were defined as the lack of an hhi dispensation before the exhaustion of the days’ supply and allotted grace period. a grace period is the gap between the exhaustion of the days’ supply and a subsequent refill that is permitted for treatment to be considered continuous. hhis are generally dispensed in 30-days’ supply, benefit of treatment is continuously assessed, and treatment interruptions are commonly employed during hhi therapy.10 we, therefore, used grace periods of 14, 30, 60, 90, and 120 days. • hhi treatment duration was estimated as days between the index date to the end of treatment (last dispensation + days’ supply). • reinitiation was defined as ≥1 hhi dispensation after treatment interruption. • the risk of hhi treatment discontinuation at 12 months, and median time (95% confidence intervals [cis]) to treatment discontinuation was estimated via kaplan– meier survival analysis using different grace periods and stratified by type of hhi use (i.e. potential adjuvant, neoadjuvant, or both neoadjuvant and adjuvant use) using a 60-day grace period. patterns of hedgehog inhibitor (hhi) treatment interruptions and reinitiations among patients with basal cell carcinoma (bcc) in real-world clinical practice jessica j jalbert,1 chieh-i chen,1 ning wu,1 matthew g fury,1 emily ruiz,2 wenzhen ge1 1regeneron pharmaceuticals, inc., tarrytown, ny, usa; 2brigham and women’s hospital, boston, ma, usa • among patients with hhi treatment discontinuation, the risk of 12-month hhi reinitiation, median time (95% cis) to reinitiation, and the risk of treatment discontinuation following second hhi use at 12 months was estimated via kaplan–meier analysis and stratified by type of hhi use (i.e. potential adjuvant, neoadjuvant, or both neoadjuvant and adjuvant use) using a 60-day grace period. results patient demographics • a total of 526 patients who initiated hhis were included in this study (table 1). • the mean (standard deviation [sd]) age was 67.0 (15.8) years; 65.4% were men. • the proportion of patients covered by commercial insurance was 53.4%. • the majority (75.9%) of patients had bcc of the head and neck. presented at the 2020 fall clinical dermatology conference, october 29-november 1, virtual scientific meeting (encore of icpe 2020 poster presentation). table 1. baseline characteristics of patients with bcc initiating hhi treatment n=526 age, years mean (sd) 67.0 (15.8) median (q1–q3) 64.0 (56.0–81.0) male, n (%) 344 (65.4) payer, n (%) commercial 281 (53.4) medicare 245 (46.6) geographic us region, n (%)† midwest 107 (21.7) northeast 72 (14.6) south 233 (47.3) west 81 (16.4) hhi index year, n (%) 2013–2014 166 (31.6) 2015–2016 176 (33.5) 2017–2018 145 (27.6) 2019 39 (7.4) vismodegib, n (%) 522 (99.2) potential adjuvant or neoadjuvant hhi use, n (%) hhi only 366 (69.6) potential neoadjuvant 20 (3.8) potential adjuvant 117 (22.2) both‡ 23 (4.4) bcc location, n (%)# head and neck 399 (75.9) limb 140 (26.6) trunk 166 (31.6) cci score, n (%) 0 518 (98.5) ≥1 8 (1.5) †geographic data is missing for 33 (6.3%) patients. percentages are calculated per number of patients with available data. ‡surgery or radiotherapy both within 60 days before and after hhi initiation. #tumor locations are not mutually exclusive. patients can have tumors at multiple sites. cci, charlson comorbidity index (excluding cancer); q, quintile. table 3. patterns of hhi discontinuation and reinitiation using a 60-day grace period, stratified by type of hhi use first episode of hhi use hhi reinitiation following first discontinuation second episode of hhi use starting sample size, n patients discontinuing hhis, n median treatment duration, days, (95% ci) risk of discontinuation at 6 months, % (95% ci) patients reinitiating hhis, n probability of reinitiation at 12 months, % (95% ci) patients discontinuing hhis, n median treatment duration days, (95% ci) overall 526 360 144 (131–162) 60.1 (55.0–64.6) 75 19.7 (15.0–24.2) 53 118 (89–172) potential neoadjuvant use 20 16 107 (86–na) 52.0 (23.4–69.9) 2 16.9 (0–35.9) 2 183 (114–na) potential adjuvant use 117 82 128 (118–171) 63.3 (52.1–71.9) 21 22.0 (11.7–31.1) 16 118 (63–na) both 23 15 90 (40–na) 71.7 (39.3–86.9) 3 13.3 (0–28.9) 2 89 (51–na) hhis only 366 247 148 (134–172) 59.0 (52.7–64.4) 49 19.4 (13.7–24.9) 33 122 (87–174) †surgery or radiation both within 60 days before and after hhi initiation. na, not applicable due to small patient numbers. table 2. patterns of hhi reinitiation among patients discontinuing hhis grace period probability of reinitiation following first hhi discontinuation time to second hhi discontinuation among those who reinitated hhis patients discontinuing hhis, n patients reinitiating hhis, n probability of reinitiation at 12 months, % (95% ci) patients discontinuing hhis, n median treatment duration, days, (95% ci) 14-day 425 170 40.9 (35.6–45.7) 145 64 (59–81) 30-day 387 105 27.0 (21.9–31.7) 80 97 (81–136) 60-day 360 75 19.7 (15.0–24.2) 53 118 (89–172) 90-day 341 61 15.8 (11.4–20.1) 43 137 (112–189) 120-day 322 53 13.6 (9.3–17.6) 34 171 (114–318) 1.00 0.75 0.50 0.25 0 0 90 180 270 360 450 14-day 30-day 60-day 90-day 120-day 94 (90–109) 123 (115–135) 144 (131–162) 156 (142–178) 172 (155–190) 78.8 (74.5–82.4) 68.3 (63.4–72.5) 60.1 (55.0–64.6) 56.1 (51.0–60.7) 52.5 (47.4–57.2) grace period median treatment duration, days (95% cis) risk of discontinuation at 6 months, % (95% cis) 540 630 720 810 900 990 1080 1170 526v30::all 302 112 50 21 9 8 7 3 1 1 1 1 1 526v14::all 255 79 30 16 7 6 5 3 1 1 1 1 1 526v60::all 324 137 67 17 11 10 7 5 3 3 2 1 1 526v90::all 334 149 82 34 15 13 10 6 4 3 2 1 1 526v120::all 343 160 87 38 19 16 11 7 4 3 2 1 1 c u m u la ti ve r is k o f h h i tr e a tm e n t d is c o n ti n u a ti o n time in days number at risk s tr a ta 0 90 180 270 360 450 540 630 720 810 900 990 1080 1170 time in days v30::all v14::all v60::all v90::all v120::allstrata figure 1. hhi treatment discontinuation using different grace periods v14, 14-day grace period; v30, 30-day grace period; v60, 60-day grace period; v90, 90-day grace period; v120, 120-day grace period. limitations • unable to distinguish between permanent versus temporary discontinuation of hhi treatment. • information pertaining to reasons for discontinuing hhi treatment as well as disease severity were not available. • there was no information regarding indication of hhi treatment, i.e. whether it was used as neoadjuvant or adjuvant therapy. type of hhi treatment • the majority of patients (99.2%) initiated hhi therapy with vismodegib. • most patients (69.6%) were treated solely with hhis. hhis were used as adjuvant therapy in 22.2% of patients and neoadjuvant therapy in 3.8% of patients. patterns of hhi discontinuations using different grace periods • risk of treatment discontinuation at 6 months ranged from 78.8% when requiring a 14-day grace period to 52.5% when requiring a 120-day grace period (figure 1). • median treatment durations were 94 days (95% ci: 90–109) using a grace period of 14 days, 144 days (95% ci: 131–162) using a grace period of 60 days, and 172 days (95% ci: 155–190) using a grace period of 120 days (figure 1). patterns of hhi reinitiation using different grace periods • the risk of hhi reinitiation at 12 months was 40.9% (95% ci: 35.6–45.7) using a grace period of 14 days, 19.7% (95% ci: 15.0–24.2) using a grace period of 60 days, and 13.6% (95% ci: 9.3–17.6) using a grace period of 120 days (table 2). • among patients reinitiating hhis, median time to subsequent discontinuation was 64 days (95% ci: 59–81) using a grace period of 14 days, 118 days (95% ci: 89–172) using a grace period of 60 days, and 171 days (95% ci: 114–318) using a grace period of 120 days (table 2). patterns of hhi discontinuations using a 60-day grace period, stratified by type of hhi use • risk of treatment discontinuation at 6 months was 52.0% (95% ci: 23.4–69.9) with potential neoadjuvant use and 63.3% (95% ci: 52.1–71.9) with potential adjuvant use (table 3). • median treatment duration from hhi initiation to first treatment discontinuation was 107 days (95% ci: 86–not applicable [na]) with potential neoadjuvant use, and 128 days (95% ci: 118–171) with potential adjuvant use (table 3). patterns of hhi reinitiation using a 60-day grace period, stratified by type of hhi use • the risk of subsequent hhi reinitiation was 16.9% (95% ci: 0–35.9) with potential neoadjuvant hhi use, and 22.0% (95% ci: 11.7–31.1) with potential adjuvant hhi use (table 3). • median treatment duration following hhi reinitiation was 183 days (95% ci: 114–na) with potential neoadjuvant hhi use and 118 days (95% ci: 63–na) with potential adjuvant hhi use (table 3). p u r p o s e high dose rate electronic brachytherapy (ebx) provides a non-surgical treatment option for nonmelanoma skin cancer (nmsc). this matched-pair cohort study compared the outcomes of treatment with ebx to those of mohs micrographic surgery (mms) in patients with nmsc. m e t h o d s all patients who had already received ebx for nmsc at 4 clinical sites and met the eligibility criteria were invited to participate. ebx was previously administered using the xoft® axxent® electronic brachytherapy system® (xoft, inc., a subsidiary of icad, inc. san jose, ca). standard surface applicators (xoft, inc.) included sizes 10, 20, 35, and 50 mm in diameter and ebx was administered in 8-10 fractions twice per week, with a dose per fraction of 4, 4.5 or 5 gy, to an average depth of 3mm. mms was previously performed by clinicians who had completed mohs fellowship training, and surgeries were conducted according to guidelines of the acms. the ebx participants were individually matched with mms patients based on patient age, lesion size (≤1cm, >1cm ≤2cm, >2cm ≤3 cm) type, and location (head, nose, torso, upper extremity, lower extremity), and treatment dates. eligibility criteria included: completion of ebx or mms for nmsc ≥3 years prior to enrollment; age >40 years; pathological diagnosis confirmed (scc, bcc) prior to treatment; cancer stage 0-2. exclusion criteria included: target area adjacent to a burn scar; surgical resection of the cancer prior to ebx; known metastatic disease. data were collected prospectively at an office visit, during which patients were clinically evaluated by the physician who had conducted the ebx or mms, and each participant completed a questionnaire. results the 369 patients (188 in the ebx treatment group and 181 in the mms treatment group) had 416 lesions (208 in the ebx group and 208 in the mms group), including 226 basal cell carcinomas (bcc) and 190 squamous cell carcinomas (scc). most patients were caucasian (98.9% and 99.5%) and male (65.4% and 66.3%) of median age 80.7 (ebx) and 76.8 years (mms). most lesions were size >1 cm and ≤2 cm, and located on the head (ear/eyelid/face/neck/lip/scalp), 59.2% in each group. at follow up, 66.7% of ebx and 68.8% showed a relatively invisible scar (p=ns). 99.5% of ebx and 100.0% of mms-treated lesions were recurrence-free (p=ns). physicians rated cosmesis as “excellent” or “good” in 97.6% and 95.7% of ebxtreated and mms-treated lesions respectively (p=ns). c o n c lu s i o n recurrence rates and patient reported outcomes with ebx and mms were similar at a mean of 3.4 years following treatment of nmsc. comparison of electronic brachytherapy and mohs micrographic surgery for the treatment of early-stage non-melanoma skin cancer: a matched pair cohort study a. rakesh patel, md; b. robert strimling, md; c. stephen doggett, md; d. mark willoughby, md and erick mafong, md; e. kenneth miller, md, pc; f. lawrence dardick, md a. good samaritan radiation oncology, los gatos, ca; b. strimling dermatology, laser vein institute, las vegas, nv; c. aegis oncology, tustin, ca; d. san diego dermatology and laser institute, san diego, ca; e. miller dermatology, los gatos, ca; f. berman skin institute, placerville, ca table 1. patient demographics at time of treatment variable ebx mms number of patients (%) 188 181 age (years) median 80.7 76.8 range 61.1 – 98.0 51.4 – 98.4 gender male 123 (65.4%) 120 (66.3%) female 65 (34.6%) 61 (33.7%) ethnicity caucasian/non-hispanic 186 (98.9%) 180 (99.5%) african-american 0 (0.0%) 1 (0.5%) asian/pacific islander 2 (1.1%) 0 (0.0%) prior skin cancer prior skin cancer 147 (78.2%) 136 (75.1%) types: melanoma 13 (6.9%) 8 (4.4%) bcc 135 (71.8%) 114 (63.0%) scc 105 (55.9%) 97 (53.6%) bsc 1 (0.5%) 0 (0.0%) prior surgery or treatment of another lesion 57 (30.3%) 124 (68.5%) ebx=electronic brachytherapy; mms=mohs micrographic surgery; bcc=basal cell carcinoma; scc=squamous cell carcinoma; bsc=basosquamous carcinoma table 2. lesion characteristics at time of treatment variable ebx mms number of lesions (%) 208 208 histopathology bcc 113 (54.3%) 113 (54.3%) scc 95 (45.7%) 95 (45.7%) cancer staging1 stage 0: tis, n0, m0 101 (48.6%) 76 (36.5%) stage 1: t1, n0, m0 103 (49.5%) 129 (62.0%) stage 2: t2, n0, m0 & ≤ 4 cm in diameter 4 (1.9%) 3 (1.4%) lesion size (cm) ≤ 1 cm 57 (27.4%) 57 (27.4%) > 1 cm and ≤ 2 cm 146 (70.2%) 146 (70.2%) > 2 cm and ≤ 3 cm 5 (2.4%) 5 (2.4%) lesion location head 5 (2.4%) 5 (2.4%) ear 10 (4.8%) 10 (4.8%) eyelid 5 (2.4%) 5 (2.4%) face/neck 72 (34.6) 72 (34.6) lip 4 (1.9%) 4 (1.9%) scalp 14 (6.7%) 14 (6.7%) nose 33 (15.9%) 33 (15.9%) torso 12 (5.8%) 12 (5.8%) lower extremity 23 (11.1%) 23 (11.1%) upper extremity 30 (14.4%) 30 (14.4%) ebx=electronic brachytherapy; mms=mohs micrographic surgery; bcc=basal cell carcinoma; scc=squamous cell carcinoma; t=tumor; n=nodes (lymph); m=metastases; g=grade 1. cancer staging system of the american joint committee on cancer table 3. treatment characteristics for electronic brachytherapy (ebx) number of lesions (%) 208 applicator size (mm) 10 mm 78 (37.5%) 20 mm 103 (49.5%) 35 mm 25 (12.0%) 50 mm 2 (1.0%) total received dose 32 gy 5 (2.4%) 36 gy 1 (0.5%) 40 gy 207 (99.5%) 50 gy 1 (0.5%) number of fractions 8/8 198 (95.2%) 10/10 10 (4.8%) dose per fraction 4 gy 14 (6.7%) 4.5 gy 1 (0.5%) 5 gy 193 (92.8%) table 4. treatment characteristics for mohs micrographic surgery (mms) number of lesions (%) n= 208 stages/levels required for clear margins 1 177 (85.1%) 2 30 (14.4%) 3 1 (0.5%) closure method surgical closure 192 (92.3%) secondary intension 16 (7.7%) table 5. primary endpoint: absence of local recurrence at followup visit ebx mms number of lesions (%) 208 208 absence of local recurrence 207 (99.5%) 208 (100.0%) 95% ci: 97.4% 100% 98.2% 100% p-value (fisher’s exact test): 1.000 follow-up time (years) mean ± std 3.3 ± 0.4 3.5 ± 0.5 median 3.2 3.4 range 2.6 – 4.3 2.3 – 5.0 table 6. long-term toxicities present at followup visit ebx mms number of lesions (%) 208 208 no changes, relatively invisible scar 138 (66.7%) 143 (68.8%) late toxicities: hypopigmentation 124 (59.6%) 109 (52.4%) hyperpigmentation 11 (5.3%) 4 (1.9%) erythematous scar 6 (2.9%) 15 (7.2%) telangiectasia 65 (31.4%) 23 (11.1%) hair loss 8 (3.9%) 7 (3.4%) fibrosis 3 (1.4%) 2 (1.0%) atrophy 12 (5.8%) 9 (4.3%) loss of subcutaneous tissue 7 (3.4%) 6 (2.9%) hypertrophy (excessive fibrosis) or keloid 0 (0.0%) 3 (1.4%) poor healing, ulceration, erosion 4 (1.9%) 0 (0.0%) ebx=electronic brachytherapy; mms=mohs micrographic surgery table 7. secondary endpoint: cosmesis grade at follow-up visit ebx mms number of lesions (%) 208 208 clinician cosmetic grade excellent/good 203 (97.6%) 199 (95.7%) 95% ci: 94.5% 99.2% 92.0% 98.0% p-value (χ2 test): 0.277 clinician cosmesis grade1 excellent 133 (63.9%) 142 (68.3%) good 70 (33.7%) 57 (27.4%) fair 1 (0.5%) 9 (4.3%) poor 4 (1.9%) 0 ( 0.0%) subject cosmesis grade1 excellent 140 (67.3%) 148 (71.1%) good 48 (23.1%) 50 (24.0%) fair 15 (7.2%) 10 (4.8%) poor 5 (2.4%) 0 (0.0%) (χ2 p-value = 0.277). cosmesis ratings by patients were “excellent” or “good” in 90% of ebt-treated sites and 95% of mms-treated sites 1. adapted from cox et al. table 8. results of patient satisfaction questionnaire at followup visit total score ebx n=208 mms n=208 mean ± std 54.0 ± 9.0 56.0 ± 5.3 median [range] 58.0 [10 – 60] 59.0 [38 – 60] individual questions2 treatments were convenient (5=strongly agree) 4.3 ± 1.1 5.0 [0 – 5] 4.7 ± 0.6 5.0 [2 – 5] satisfied with how well treatment worked (5=strongly agree) 4.5 ± 1.0 5.0 [0 – 5] 4.8 ± 0.5 5.0 [1 – 5] satisfied with appearance of the treated area (5=strongly agree) 4.4 ± 1.0 5.0 [0 – 5] 4.6 ± 0.7 5.0 [2 – 5] if another cancer, would use same treatment (5=strongly agree) 4.1 ± 1.4 5.0 [0 – 5] 4.6 ± 0.7 5.0 [1 – 5] have not had any skin problems with treated area (5=strongly agree) 4.5 ± 1.2 5.0 [0 – 5] 4.7 ± 0.6 5.0 [1 – 5] since treatment, frustrated about appearance of treated site (5=strongly disagree) 4.5 ± 1.1 5.0 [0 – 5] 4.6 ± 1.0 5.0 [0 – 5] since treatment, embarrassed about appearance of treated site (5=strongly disagree) 4.6 ± 0.9 5.0 [0 – 5] 4.7 ± 0.7 5.0 [1 – 5] since treatment, depressed about appearance of treated site (5=strongly disagree) 4.5 ± 1.1 5.0 [0 – 5] 4.6 ± 0.8 5.0 [0 – 5] treatment prevented me from participating in daily activities (5=strongly disagree) 4.6 ± 0.9 5.0 [0 – 5] 4.6 ± 0.9 5.0 [0 – 5] treatment made it hard to work or do what i enjoy (5=strongly disagree) 4.7 ± 0.7 5.0 [0 – 5] 4.6 ± 0.8 5.0 [0 – 5] would recommend treatment to others (5=strongly agree) 4.4 ± 1.3 5.0 [0 – 5] 4.7 ± 0.7 5.0 [0 – 5] always followed instructions related to care of treated area (5=strongly agree) 4.9 ± 0.4 5.0 [3 – 5] 4.7 ± 0.5 5.0 [2 – 5] std=standard deviation 2. a score of 5 represents the maximum positive or favorable response to each question. fc17posterxoftpatelcomparison.pdf skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 65 brief articles a case report of a primary cutaneous adenoid carcinoma: a diagnostic and management challenge trang t. vu, md, phd, bsc1, muba taher, md, frcpc1, tawny hung, md, frcpc2 1division of dermatology, department of medicine, faculty of medicine and dentistry university of alberta, alberta, ca 2division of pathology, department of laboratory medicine and pathology, university of alberta, alberta, ca adenoid cystic carcinoma (acc) is a slow growing, usually asymptomatic neoplasm most commonly associated with secretory glands. rarely is it observed as a primary tumor on the skin.1 it is unclear whether pcacc is of eccrine or apocrine origin.2 salivary gland acc rarely metastasizes to skin.3 however, acc is also observed in the lungs, breasts, prostate and cervix and identification of cutaneous acc should prompt investigations for metastasis or direct extension from salivary glands adjacent to the skin.1 further, the median age for developing pcacc is 61 years old with equal disease incidence in men and women. primary neoplastic sites include the head and neck (46%), followed by upper limbs (17%), trunk (15%) and lower limbs (13%).1,4 we report a case of pcacc that presents both as a diagnostic and management challenge. a 52 year old female presented to an outpatient dermatology clinic with an asymptomatic 5 mm skin colored, subcutaneous papule on the left mid back resembling a cyst. given the clinical resemblance to a cystic lesion, it was treated with intralesional triamcinolone. despite treatment, the lesion persisted and a biopsy was performed. histologic examination showed a dermal nodular proliferation of basaloid islands and cords separated by spaces with an amorphous pas+ material. initial pathology was interpreted as a benign sweat duct tumor, demonstrating the diagnostic challenges with these lesions. cognizant that malignant sweat gland tumors can be misread as benign lesions, a second opinion from a more experienced dermatopathologist was sought. on second opinion the diagnosis was of a malignant, low-grade, sweat duct tumor. staining of areas of ductal abstract primary cutaneous adenoid cystic carcinoma (pcacc) is a rare glandular neoplasm that mimics benign lesions both clinically and histologically making it a diagnostic challenge. although indolent, acc has potential for local regional and distant metastasis and, even after surgical excision, there is a high recurrence rate. this report outlines a case of a ppacc and reviews current therapeutic approaches. introduction case presentation https://paperpile.com/c/nzabld/aym9 https://paperpile.com/c/nzabld/yu1b https://paperpile.com/c/nzabld/gpwg https://paperpile.com/c/nzabld/aym9 https://paperpile.com/c/nzabld/aym9+xeid skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 66 figure 1. histopathologic diagnosis of pcacc. (a) hematoxylin and eosin staining showing an infiltrating intradermal basaloid tumor with a cribriform pattern and mucinous secretions (h&e, 20x). (b) positive luminal and pseudocystic spaces staining with ema (10x). (c) positive c-kit (cd117) staining around the pseudocyst (10x). differentiation showed cea+, ema+, s100+ and lmwck+ and c-kit+ (cd117) favoring the diagnosis of an acc (figure 1). the lesion was excised by wide local excision with 1.0 cm tumor free margins. a complete lymph node examination did not show any lymphadenopathy. whole body pet-ct did not show metastasis suggesting local, regional disease. management of acc remains a challenge since there is a high incidence of recurrence especially if there is perineural invasion.5 recurrence following surgical resection is around 44% with an average follow-up time of 58 months.3,5 there is no consensus on the optimal treatment of pcacc. surgical excision with adjuvant radiotherapy is routinely used for pcacc with skin-limited disease, although comparative studies have not conclusively demonstrated that adjuvant radiotherapy is superior to surgery alone.6 reported surgical modalities include local excisions, wide local excision (wle) with 1.0 – 2.0 cm safety margins and mohs surgery.2,5,7 perineural invasion and local recurrence has been reported in 76% and 44%, respectively with traditional surgical excision.5 therefore, in or practice, a wle with at least 1.0 cm margins is performed. on the head and neck, 23% of pcacc have been identified on the face and 8.6% on eyelids. mohs surgery should be considered in these cases to spare tissue and preserve function.2,5 however, pcacc can spread asymmetrically along nerves, therefore mohs surgery can have limitations for identifying margin clearance when there is perineural invasion.2 staging of pcacc should include routine lymph node examination with whole body imaging to assess for extracutaneous involvement. lymph node dissection is suggested for nodal involvement5. whole body imaging should include the head and neck since primary acc accounts for 10% of salivary glands neoplasms. the most common areas for metastasis include the lungs, bone and liver. since primary acc can arise from breast and in the discussion https://paperpile.com/c/nzabld/nc1v https://paperpile.com/c/nzabld/nc1v https://paperpile.com/c/nzabld/gpwg https://paperpile.com/c/nzabld/nc1v https://paperpile.com/c/nzabld/vzho https://paperpile.com/c/nzabld/9tza+yu1b+nc1v https://paperpile.com/c/nzabld/nc1v https://paperpile.com/c/nzabld/yu1b+nc1v https://paperpile.com/c/nzabld/yu1b https://paperpile.com/c/nzabld/nc1v skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 67 genitourinary tract, an age appropriate mammogram, pap smear and/or prostate examination should be included in the workup.2 chemotherapy is first line for advanced, metastatic acc, albeit this is not standardized.8 classical chemotherapy agents including cisplatin, 5-fluorouracil, or a combination of cisplatin, doxorubicin and cyclophosphamide are utilized for metastatic disease. several studies have shown that drugs targeting epidermal growth factor receptor or the downstream tyrosine kinases has shown some promise in treating advanced acc in a cohort of patients.8 more molecular, genetic and clinical studies are needed to identify therapeutic agents specifically targeting acc. there are no standard guidelines for followup of patients with pcacc. pcacc follows an indolent course and the reported time to recurrence following surgical excision ranges from 1 month to 35 years.3 a review of fifty cases in the literature showed that on average the cases recurred within 58 months.3 follow-up frequency may also vary depending on the presence of any metastatic disease. therefore, there is insufficient evidence to support any definitive recommendations for follow-up and this should be done on a case-by-case basis. pcacc can be diagnostically challenging owing to its indolent growth and its ability to mimic benign entities. although there is no consensus regarding management of pcacc, we suggest wle of at least 1.0 cm margins, full lymph node examination and imaging to elucidate the etiology. routine follow-up with imaging is suggested given the high incidence of recurrence. conflict of interest disclosures: none funding: none corresponding author: tawny hung md, frcpc department of laboratory medicine and pathology, university of alberta edmonton, alberta, canada phone: 780-407-8822 email: tawny.hung@gmail.com references: 1. dillon pm, chakraborty s, moskaluk ca, joshi pj, thomas cy. adenoid cystic carcinoma: a review of recent advances, molecular targets, and clinical trials. head neck. 2016;38(4):620627. 2. xu yg, hinshaw m, longley bj, ilyas h, snow sn. cutaneous adenoid cystic carcinoma with perineural invasion treated by mohs micrographic surgery-a case report with literature review. j oncol. 2010;2010:469049. 3. naylor e, sarkar p, perlis cs, giri d, gnepp dr, robinson-bostom l. primary cutaneous adenoid cystic carcinoma. j am acad dermatol. 2008;58(4):636-641. 4. ramakrishna r, raza sm, kupferman m, hanna e, demonte f. adenoid cystic carcinoma of the skull base: results with an aggressive multidisciplinary approach. j neurosurg. 2016;124(1):115-121. 5. tiwari r, agarwal s, sharma m, gaba s. primary cutaneous adenoid cystic carcinoma: a clinical and histopathological mimic: a case report. oral and maxillofacial surgery cases. 2018;4(4):175179. doi:10.1016/j.omsc.2018.09.002 6. jaso j, malhotra r. adenoid cystic carcinoma. arch pathol lab med. 2011;135(4):511-515. 7. cacchi c, persechino s, fidanza l, bartolazzi a. a primary cutaneous adenoid-cystic carcinoma in a young woman. differential diagnosis and clinical implications. rare tumors. 2011;3(1):7-9. doi:10.4081/rt.2011.e3 8. chae yk, chung sy, davis aa, et al. adenoid cystic carcinoma: current therapy and potential therapeutic advances based on genomic profiling. oncotarget. 2015;6(35):37117-37134. conclusion https://paperpile.com/c/nzabld/yu1b https://paperpile.com/c/nzabld/7o92 https://paperpile.com/c/nzabld/7o92 https://paperpile.com/c/nzabld/gpwg https://paperpile.com/c/nzabld/gpwg http://paperpile.com/b/nzabld/aym9 http://paperpile.com/b/nzabld/aym9 http://paperpile.com/b/nzabld/aym9 http://paperpile.com/b/nzabld/aym9 http://paperpile.com/b/nzabld/aym9 http://paperpile.com/b/nzabld/aym9 http://paperpile.com/b/nzabld/aym9 http://paperpile.com/b/nzabld/yu1b http://paperpile.com/b/nzabld/yu1b http://paperpile.com/b/nzabld/yu1b http://paperpile.com/b/nzabld/yu1b http://paperpile.com/b/nzabld/yu1b http://paperpile.com/b/nzabld/yu1b http://paperpile.com/b/nzabld/yu1b http://paperpile.com/b/nzabld/gpwg http://paperpile.com/b/nzabld/gpwg http://paperpile.com/b/nzabld/gpwg http://paperpile.com/b/nzabld/gpwg http://paperpile.com/b/nzabld/gpwg http://paperpile.com/b/nzabld/gpwg http://paperpile.com/b/nzabld/xeid http://paperpile.com/b/nzabld/xeid http://paperpile.com/b/nzabld/xeid http://paperpile.com/b/nzabld/xeid http://paperpile.com/b/nzabld/xeid http://paperpile.com/b/nzabld/xeid http://paperpile.com/b/nzabld/xeid http://paperpile.com/b/nzabld/nc1v http://paperpile.com/b/nzabld/nc1v http://paperpile.com/b/nzabld/nc1v http://paperpile.com/b/nzabld/nc1v http://paperpile.com/b/nzabld/nc1v http://paperpile.com/b/nzabld/nc1v http://paperpile.com/b/nzabld/nc1v http://dx.doi.org/10.1016/j.omsc.2018.09.002 http://paperpile.com/b/nzabld/vzho http://paperpile.com/b/nzabld/vzho http://paperpile.com/b/nzabld/vzho http://paperpile.com/b/nzabld/vzho http://paperpile.com/b/nzabld/9tza http://paperpile.com/b/nzabld/9tza http://paperpile.com/b/nzabld/9tza http://paperpile.com/b/nzabld/9tza http://paperpile.com/b/nzabld/9tza http://paperpile.com/b/nzabld/9tza http://paperpile.com/b/nzabld/9tza http://dx.doi.org/10.4081/rt.2011.e3 http://paperpile.com/b/nzabld/7o92 http://paperpile.com/b/nzabld/7o92 http://paperpile.com/b/nzabld/7o92 http://paperpile.com/b/nzabld/7o92 http://paperpile.com/b/nzabld/7o92 http://paperpile.com/b/nzabld/7o92 skin may 2018 volume 2 issue 3 copyright 2018 the national society for cutaneous medicine 205 compelling comments cocaine and the local anesthetic tyler marion bs mba a , jake alan gibbons bsa a a the university of texas medical branch, galveston, tx the first use of local anesthetics dates back to the 16th century when bernabe cobo, a spanish missionary, noted that toothaches could be alleviated by chewing coca leaves. 1 however, the active component remained a mystery until 1860 when german chemist, albert niemann, isolated and termed the component ‘cocaine’. 1 the discovery of cocaine sparked great interest within the medical community. amongst those interested was founder of psychoanalysis, sigmund freud. freud experimented with cocaine, erroneously reporting that cocaine produced no compulsive desire to reuse the substance. 2 during this same time period, dr. carl koller, a viennese ophthalmologist and acquaintance of freud, pioneered the use of cocaine as an anesthetic through his experiments focused on the cornea of dogs and guinea pigs. 1 cocaine was used for a nerve block for the first time in 1884 by william halsted, one of the founders of john hopkins school of medicine. 2 advancements were made using cocaine as an anesthetic, including the first spinal anesthesia performed by james corning. 2 however, the toxicities and addictive potential of cocaine were identified, leading to decreased use as an anesthetic. researchers were prompted to experiment with other agents. an early breakthrough came in 1905, when alfred einhorn, a german chemist, synthesized procaine. a derivative of paraaminobenzoic acid, procaine gained popularity due to its wide safety margin, but carried the risk of allergic reactions in patients. 3 in 1943, nils löfgren and bengt lundqvist from stockholm university developed lidocaine, a long-acting anesthetic agent without the propensity of allergic reactions. 1 lidocaine gained popularity amongst clinicians and became the ubiquitous drug that it is today in dermatology. dermatologists commonly administer intradermal injections of lidocaine for skin biopsies, lesion excisions, and soft tissue augmentation. although cocaine is no longer used for numbing effects, it paved the way for the development of local anesthetics still used today. conflict of interest disclosures: none funding: none corresponding author: tyler marion, bs, mba 301 university blvd, galveston, tx 77555 817-501-9357 tmarion9@gmail.com skin may 2018 volume 2 issue 3 copyright 2018 the national society for cutaneous medicine 206 references: 1. walsh a, walsh s. local anaesthesia and the dermatologist. clin exp dermatol. 2011;36(4):337-343. 2. redman m. cocaine: what is the crack? a brief history of the use of cocaine as an anesthetic. reg anesth pain med. 2011;1(2). 3. grekin rc, auletta mj. local anesthesia in dermatologic surgery. j am acad dermatol. 1988;19(4):599-596. skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 293 brief article a rare presentation of concomitant alopecia areata and vitiligo in a teenager antonio jimenez, bs1, paige hoyer, md2, lindy ross, md2 1the university of texas medical branch, school of medicine 2the university of texas medical branch, department of dermatology alopecia areata (aa) and vitiligo are two chronic, immune-mediated skin conditions. the clinical presentation of aa is inflammatory, patchy hair loss. in contrast, vitiligo presents as circumscribed, depigmented macules or patches of skin in a sporadic or segmental distribution. the two conditions are common; the lifetime incidence of aa and vitiligo are 2% and 1%, respectively.1,2 however, coexistent disease is rare. while their clinical presentations differ, their pathogenesis is believed to be similar. we present a 13-year-old female who presented to the dermatology clinic with the classic presentation of aa. the patient then developed depigmented patches of hair on her scalp and right eyelash, concerning for aa-vitiligo disease overlap a 13-year-old caucasian female with no pertinent past medical history presented to the dermatology clinic for evaluation of bald abstract introduction: alopecia areata (aa) and vitiligo are two chronic, autoimmune skin diseases. while these two conditions are common, their co-existence is rare. case presentation: a 13-year-old caucasian female presented to the dermatology clinic with a 1-2month history of hair loss on her occipital scalp. the patient was diagnosed with aa and prescribed topical mometasone 1% lotion twice daily and pulse-dose prednisolone solution 12 ml 1 day per month for 3 months. at her 3-month follow-up, the patient reported new-onset hair depigmentation. on physical examination, the patient’s occipital scalp and right eyelash demonstrated a depigmented patch of hair, concerning for vitiligo. the patient was diagnosed with concomitant disease and topical tofacitinib was added to her treatment regimen. discussion/conclusion: the colocalization of aa and vitiligo is rare, and the presentation suggests an underlying pathogenic link between the two skin diseases. while the definitive immunologic pathway remains unknown, researchers have narrowed down inflammatory markers involved in the development of both conditions, including cd8+ cytotoxic t-cells, interferon gamma (ifn-ɣ), and ifnɣ-induced chemokines. we present a 13-year-old female patient who presented to the clinic with scalp alopecia and later developed overlying scalp and eyelash vitiligo. the rare nature of the patient’s presentation makes concomitant disease a therapeutic challenge and can impose significant psychological distress to a pediatric patient. introduction case presentation skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 294 spots on her scalp. she said she first noticed hair loss 1-2 months ago, and she had not used a new scalp or hair treatment. the patient denied weight changes, dry skin, heat/cold intolerance, trichotillomania, pruritus, pain, and bleeding from the site. the patient’s family history is pertinent for a paternal grandmother and paternal aunt with thyroid disease and psoriasis. on physical examination, the patient demonstrated patchy, non-scarring hair loss on the right side of the scalp and scalp vertex. she was diagnosed with alopecia areata and offered both intralesional and topical treatment. at this time, she declined steroid injections and was prescribed mometasone 0.1% lotion twice daily to affected areas and pulse-dose prednisolone solution 12 ml daily for 1 day of the month for 3 months. at her 1-month follow-up, the patient reported new areas of hair loss on the left and occipital scalp and diffuse scaling, despite consistent use of mometasone. she was encouraged to continue her treatment regimen at this visit. at her 3-month follow-up, the patient reported hair growth since her last visit. on physical examination, a patch of depigmented hair was discovered on her occipital scalp and right eyelash (fig 1a, 1b). the patch of depigmentation was suspicious for vitiligo, and the patient was instructed to add crisaborole 2% ointment to the white areas daily. the patient was unable to afford the ointment, and she was instead prescribed topical tofacitinib for the white areas. she was scheduled for a followup in 4-6 weeks. alopecia areata (aa) is an organ-specific, inflammatory, and non-scarring form of hair loss. the condition is caused by cd4+ and cd8+ t-cell-mediated destruction of anagen-phase hair follicles.3 aa often figure 1a. alopecia areata with concomitant vitiligo on occipital scalp. the patient demonstrated patchy hair loss with overlying depigmented patches of skin and hair on her posterior scalp concerning for vitiligo. figure 1b. vitiligo on right eyelash. the patient demonstrated depigmented hair growth in her right eyelash presents in patients aged 30-40 and there is no sex predominance; the degree of disease ranges from mild, circumscribed patches of alopecia to complete scalp and body hair loss.3 the etiology and pathogenesis of the disease is unknown, but it is theorized that there is an intermingling between genetic, discussion skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 295 environmental (e.g., stress, trauma, viral illnesses), hormonal, and autoimmune factors that predispose patients to the chronic disorder. in contrast, vitiligo is a chronic, immune-mediated depigmenting skin condition; it is due to cd8+ destruction of epidermal melanocytes. this condition often presents in the pediatric population, with over half of cases reported before age 20.2 vitiligo and aa both fall under the spectrum of autoimmune diseases. patients with either disease are inclined to suffer from other autoimmune cutaneous and systemic diseases, including psoriasis, lichen planus, atopic dermatitis, systemic lupus erythematous, autoimmune thyroiditis, and diabetes mellitus.3 the concomitant presentation of both aa and vitiligo is uncommon. however, the colocalization of aa and vitiligo is rarer, and its unique presentation has piqued dermatologists’ interest in the clinical and immunologic commonalities between the two diseases. the clinical presentation of aa has been theorized to be interconnected with melanocytes and pigmentation. in aa, autoimmune destruction of hair follicles is specific to pigmented hair; white hair remains unscathed. in addition, after aa has been treated, depigmented hair grows first.4 in vitiligo, the active re-pigmentation process first begins at the follicular and peri-follicular region of hair shafts.4,5 these clinical manifestations support evidence of an underlying link between the two diseases. therefore, investigations that revolve around the identification of a common pathogenic pathway are underway. it is well-elucidated that cd8+ cytotoxic tcells have a role in the destruction of hair follicles and melanocytes in aa and vitiligo, respectively; however, the two diseases have more striking pathogenic similarities.6 rork et. al suggest that the initiating trigger for both diseases is increased reactive oxygen species and cellular stress levels. in addition, mice models have demonstrated that interferon-gamma (ifn-ɣ) and ifn-ɣinduced cytokines are additional drivers in disease pathogenesis.7 kumar et. al also proposed the notion that localized, proinflammatory th1 cell reactions or the inactivation of an immune suppressor mechanism leads to concomitant damage to the melanocytes and hair follicles, explaining the regional overlap of the disease in our patient.4 to date, the exact pathogenic link has not been determined. the management of aa includes topical and intra-lesional corticosteroids, topical calcineurin inhibitors, and narrow-band ultraviolet b phototherapy (nb-uvb). the treatment of vitiligo is similar. however, the straightforward management of each disease becomes challenging when they present concurrently. in literature, there are few details regarding treatment and followup for patients with concomitant disease. harris et. al reported success with the use of ruxolitinib, a janus kinase (jak) inhibitor, in a patient with coexistent aa and vitiligo. jak inhibitors interfere with ifn-ɣ signaling and ifn-ɣ-induced chemokines, which could explain its success in the treatment of both conditions.8 in our case, the patient presented a therapeutic challenge because of her concomitant disease. her vitiligo was present on her right eyelash – a location which led us to choose a steroid-sparing agent such as crisaborole 2% ointment as a first-line treatment option for her vitiligo. while the fda has approved crisaborole for atopic dermatitis in adults and children, case reports have noted its success in the treatment of vitiligo.9 to our knowledge however, no studies have reported improvement of alopecia areata with crisaborole. while other steroid-sparing agents such as jak inhibitors can be used skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 296 for the initial management of concomitant disease, the patient’s insurance coverage prevented us from considering these agents as first-line therapy. additional studies should be completed to determine the best management for this rare presentation. we present a 13-year-old female who presented to the dermatology clinic for patchy hair loss and subsequent development of overlying scalp and eyelash vitiligo. the colocalization of the two diseases in her scalp is rare, and studies have proposed a common immunologic mechanism that drives the regional presentation of her disease. however, the exact pathway has not been elucidated. this presentation remains a therapeutic challenge because of limited research on adequate treatment regimens and its ability to cause significant psychosocial distress to the patient. conflict of interest disclosures: none funding: none corresponding author: antonio jimenez, bs 301 university blvd galveston, tx 77555 phone: 956-763-5779 email: anrjimen@utmb.edu references: 1. miteva m, villasante a. epidemiology and burden of alopecia areata: a systematic review. clinical, cosmetic and investigational dermatology. 2015:397. 2. matin r. vitiligo in adults and children. bmj clin evid. 2011;2011:1717. 3. barahmani n, schabath mb, duvic m. history of atopy or autoimmunity increases risk of alopecia areata. journal of the american academy of dermatology. 2009;61(4):581-591. 4. kumar s, mittal j, mahajan b. colocalization of vitiligo and alopecia areata: coincidence or consequence? international journal of trichology. 2013;5(1):50. 5. cui j, shen l-y, wang g-c. role of hair follicles in the repigmentation of vitiligo. journal of investigative dermatology. 1991;97(3):410416. 6. harris je. vitiligo and alopecia areata: apples and oranges? experimental dermatology. 2013;22(12):785-789. 7. rork jf, rashighi m, harris je. understanding autoimmunity of vitiligo and alopecia areata. current opinion in pediatrics. 2016;28(4):463-469. 8. harris je, rashighi m, nguyen n, et al. rapid skin repigmentation on oral ruxolitinib in a patient with coexistent vitiligo and alopecia areata (aa). journal of the american academy of dermatology. 2016;74(2):370-371. 9. tausend, w., hoyer, p., arnold, m., wagner, k., ross, l., goodwin, b. p., & wilson, j. m. (2019). successful treatment of vitiligo with crisaborole 2% ointment. skin the journal of cutaneous medicine, 3(2), 111-113. conclusion safety and efficacy of a-101 hydrogen peroxide topical solution 40% in adults with seborrheic keratosis: results from the phase 3, randomized, double-blind, vehicle-controlled study zoe d. draelos, md,1 steven e. kempers, md,2 stacy r. smith, md,3 david c. wilson, md,4 christopher v. powala,5 mark bradshaw, phd,6 esther estes, md, mph,5 stuart d. shanler, md, faad, facms5 1dermatology consulting services, high point, nc; 2minnesota clinical study center, fridley, mn; 3california dermatology & clinical research institute, encinitas, ca; 4the education and research foundation, inc., lynchburg, va; 5aclaris therapeutics, malvern, pa; 6global consulting partners in medical biometrics, new york, ny introduction • seborrheic keratosis (sk) is a common cutaneous lesion that affects more than 83 million americans,1 particularly those who are middle-aged and older. while benign, these lesions are cosmetically unacceptable to many patients. • malignancy concerns following the appearance of lesions act as a primary driver for a patient to seek medical advice. • removal of sks is often performed for cosmetic reasons, but it may be indicated for inflamed, pruritic, or painful lesions. • prior to december 2017, there was no us fda–approved drug for the treatment of sks. ablative/destructive procedures (eg, cryosurgery, electrodessication/curettage, etc) had been available; however, their efficacy and safety have not been rigorously evaluated in well-controlled clinical trials, and they often involve burning, cutting, or freezing. • a noninvasive, well-tolerated, topical agent for the removal of sks is an important unmet need. • a-101 is a patented topical formulation based on a high concentration of hydrogen peroxide (40% w/w) for asymptomatic sk.2 • phase 2 studies showed that a numerically greater percentage of subjects achieved lesion clearance when treated with a-101 40% versus a-101 32.5%; both concentrations achieved significantly greater clearance than placebo.3 • the purpose of this study (a-101-sebk-301; nct02667236) was to evaluate the safety and efficacy of a-101 40% versus its matching vehicle for the treatment of sk. materials and methods patients and study design • multicenter, phase 3, randomized, double-blind, vehicle-controlled study. patients were randomized 1:1 to receive a-101 or matching vehicle. • eligible patients: aged ≥ 18 years with 4 eligible lesions, identified by study investigator. • eligible target lesions were stable, typical sks, measuring 5-15 mm in both width and length, 1-2 mm in thickness, and physician’s lesion assessment (pla) grade ≥ 2 (table 1).4 patients were required to present with ≥ 1 sk on the trunk or extremities and ≥ 1 sk on the face. — target sks could not be on the eyelid, within 5 mm of the orbital rim, in an intertriginous area, or pedunculated. table 1: validated physician’s lesion assessment (pla)3 scale grade descriptor 0 clear: no visible sk 1 near clear: a visible sk with a surface appearance different from the surrounding skin (not elevated) 2 thin: a visible sk (≤ 1 mm) 3 thick: a visible sk (> 1 mm) table 2: > 90% of sks without local dyspigmentation or scarring no reaction mild moderate severe hypopigmentation a-101 40% vehicle 97.7% 99.9% 2.3% 0.1% 0.0% 0.0% 0.0% 0.0% hyperpigmentation a-101 40% vehicle 93.8% 99.8% 5.6% 0.1% 0.6% 0.1% 0.0% 0.0% scarring a-101 40% vehicle 99.3% 100.0% 0.6% 0.0% 0.1% 0.0% 0.0% 0.0% conclusions • a-101 (hydrogen peroxide) topical solution, 40% (w/w) is a safe, effective, and well-tolerated treatment for seborrheic keratoses (figure 3). • for sks on the face and cosmetically sensitive locations, a-101 was highly effective, with very low occurrence of hypopigmentation and/or scarring. • on december 14, 2017, a-101 (hydrogen peroxide) topical solution, 40% (w/w) was approved by the fda as the first and only topical treatment for raised seborrehic keratoses. references 1. bickers dr, et al. j am acad dermatol. 2006;55:490-500. 2. simionescu o, et al. j cell mol med. 2012;16:1223-1231. 3. dubois jc, et al. dermatol surg. 2017; doi: 10.1097/dss.0000000000001302. 4. data on file. aclaris therapeutics inc., 2014, malvern, pa, usa. acknowledgments this study was funded by aclaris therapeutics, inc. editorial support for this poster was provided by parexel and funded by aclaris therapeutics, inc. figure 3: patient photos of sk, before and after a-101 treatment female, forehead (met primary endpoint) female, temple (did not meet primary endpoint) pla 3 baseline pla 3 baseline clear pla 0 day 106 near clear pla 1 day 106 • all treatments were performed by a nonphysician subinvestigator to maintain blinding. after initial treatment on day 1, sks with a pla score > 0 were retreated on day 22. at day 106, the investigator assessed the sks using the validated pla scale. endpoints • primary efficacy endpoint: percent of patients with complete clearance (pla = 0) of all 4 sks at 106 days after first treatment. • secondary endpoint: percent of patients with complete clearance (pla = 0) in at least 3 of 4 sks. • exploratory endpoints: — mean per-patient percent of sks judged clear/near clear (pla ≤ 1). — mean per-patient percent of sks on the face judged clear/near clear (pla ≤ 1). • safety: adverse events (aes), local skin reactions. results • a total of 450 patients were enrolled—220 of 223 and 226 of 227 patients randomized to a-101 and vehicle, respectively, completed the study. • demographic characteristics were similar across all treatment groups. • mean age of patients was 69 years (range, 42–90). 59% of subjects were women, and 97.8% (440) were caucasian. • fitzpatrick types 1 to 5 were represented: — type 1: 72 (16.0%); type 2: 211 (46.9%); type 3: 123 (27.3%); type 4: 40 (8.9%); type 5: 4 (0.9%). efficacy primary and secondary endpoints • significantly more patients receiving a-101 completely cleared (pla = 0) all 4 of 4 sks (4.0% vs 0%, p < 0.002) and 3 of 4 sks (13.5% vs 0%, p < 0.0001) versus vehicle in the primary and secondary endpoints, respectively, at day 106 (figure 1). exploratory endpoints • significantly higher mean per-patient percentage of sks achieving clear/near clear (pla ≤ 1) was observed in the a-101 arm (48% vs 10% at day 106) (figure 2a). • significantly higher mean per-patient percentage of facial sks achieving clear/near clear (pla ≤ 1) was also observed in the a-101 arm (64% vs 15% at day 106) (figure 2b). figure 1: percentage of patients with complete clearance (pla 0) of all 4 sks (a) and at least 3 of 4 sks (b) 0 2 1 3 4 5 6 7 8 9 10 day 106 0 a b 0 day 106 p at ie n ts , % 0 6 8 10 12 14 4 2 16 p at ie n ts , % 4% 13% p < 0.002 p < 0.0001 vehicle a-101 40% 0 20 10 30 40 50 60 70 se b or rh e ic k e ra to se s, % 0 30 20 10 40 50 60 70 se b or rh e ic k e ra to se s, % 48% 64% 10% 15% a b day 106 day 106 vehicle a-101 40% figure 2: mean per-patient percent of sks (a) or facial sks (b) judged to be clear/near clear (pla ≤ 1) safety • aes were comparable between groups: 54 (24.2%) patients in the a-101 group versus 45 (19.8%) patients in the vehicle group. — the most frequently reported treatment-emergent aes were nasopharyngitis (1.3% a-101 vs 3.1% vehicle), bronchitis (1.3% a-101 vs 0.4% vehicle), and upper respiratory tract infection (0.4% a-101 vs 1.3% vehicle). — 4 (1.8%) patients in the a-101 group had 4 serious aes (saes) versus 6 (2.6%) patients in the vehicle group who had 7 saes. all saes were considered not related to study medication. • local skin reactions were predominantly mild and had generally resolved by day 106 (table 2). • at all visits, atrophy, erosion, hypopigmentation, scarring, or ulceration were reported for ≤ 4% of sks. gs1444 236102 aclaris winter clinical a101 3.5ft x 7ft s05.indd 1 20/12/2017 10:33 skin july 2018 volume 2 issue 4 copyright 2018 the national society for cutaneous medicine 219 original research the comparative effects of various moisturizers on epidermal barrier function recovery after bathing in atopic dermatitis vy shi md a , n foolad bs b , j ornelas md c , w burney mbbs b , melody maarouf mhs d , l hassoun md c , g monico bs c , n takeda md c , s bosanac md c , lf eichenfield md e,f , rk sivamani md ms cat b,g a department of medicine, division of dermatology, university of arizona, tucson, az b department of dermatology, university of california davis, sacramento, ca c university of california davis school of medicine, sacramento, ca d university of arizona college of medicine, tucson, az e departments of pediatrics and dermatology, university of california san diego, school of medicine san diego, ca f pediatric and adolescent dermatology, rady children’s hospital, san diego, ca g department of biological sciences, california state university, sacramento, ca abstract background/aims: an important pillar of ad management involves moisturizer application following bathing to restore epidermal barrier function (ebf). in this study, we aim to bring additional evidence to the “soak-and-smear” regimen, comparing ebf recovery by various moisturizers following bathing in ad and healthy subjects. methods: volar forearms of 10 ad patients and 10 healthy controls were immersed in water for 10 minutes to simulate bathing. immediately after bathing, ceramide-containing emollient (cer), a humectant (10% glycerin, gly), an occlusant (white petrolatum, petr), and aloe vera 5% extract (aloe) were applied to separate test sites on the forearm. one test site did not receive any moisturizer and served as control. ebf parameters (hydration, tewl, and ph) were recorded at baseline, and 15, 30, and 60-minutes post-bathing. results: ad and controls shared similar trends. aloe had the most significant ph decrease while gly had the highest ph increase. hydration significantly increased in all moisturizers compared to control. gly led to the highest increase, peaking at 15-minutes for both ad and healthy subjects. ad subjects had higher hydration following cer than healthy subjects throughout the entire study. all four moisturizers increased tewl compared to control, though petr had the lowest initial tewl increase. conclusion: all moisturizers had an immediate effect on improving sc hydration. their initial effects on tewl increase recovers toward control levels by 60-minutes. future studies are needed to examine the effect of repeated moisturizer post-bathing over longer study periods. skin july 2018 volume 2 issue 4 copyright 2018 the national society for cutaneous medicine 220 atopic dermatitis (ad) is a remittingrelapsing inflammatory skin condition characterized by xerosis, itching, and eczematous lesions. patients have defective epidermal barrier function (ebf) associated with decreased ceramide levels and stratum corneum (sc) hydration, and increased transepidermal water loss (tewl) and ph. 1 management recommendations emphasize the “soak and smear” technique, by applying moisturizers immediately after bathing. 2 few studies have reported the quantitative effect of moisturizers on ebf following bathing, and even less have compared the various ingredients. the goal of this study is to compare ebf recovery among various moisturizers after bathing in ad and healthy subjects. the moisturizers tested encompass a wide spectrum of barrierrepairing properties and include a ceramidecontaining emollient (cer), humectant (10% glycerin, gly), occlusive (white petrolatum, petr), and aloe vera 5% extract (aloe). the study was approved by the institutional review board at the university of california, davis (irb# 523979) and registered on clinicaltrials.gov (nct02594969). following informed consent, ten patients with ad (mean age 26.3 years, range 12-45 years; 5 mild, 3 moderate, 2 severe) and ten healthy volunteers (mean age 28.5 years, range 2234 years) participated in this study. cer (valeant pharmaceuticals, usa) and petr (covidien, usa) were purchased commercially. gly 10% solution was prepared in phosphate-buffered saline. for aloe extraction, 2.5g of fresh aloe vera leaf was added to 50ml sterile water, heated at 80c while stirred for 30-minutes, cooled to room temperature, then centrifuged at 2000rpm for 10 minutes followed by serial filtering. testing was conducted on volar forearms. none of the subjects bathed or applied topical moisturizers or medications for 12hours prior to the study session. test arms were immersed in room temperature nonionized water for 10-minutes, followed by dab-drying with towels. ebf including hydration (moisturemeter sc, delfin technologies, inc., usa), tewl (tewameter, courage and khazaka, germany) and ph (dry skin ph meter, hanna instruments, usa) were measured immediately post-immersion. within 3minutes post-bath, 0.2ml of each of the four moisturizers were applied to separate 1inch 2 spots on the forearm, and gently massaged until no residual product was visible. the control spot did not receive any moisturizer. ebf were measured again at 15, 30 and 60-minutes post-bathing. participants were asked to report skin discomfort, including itching, burning or pain at any time during the study. outcome measures are presented in table 1. ebf status changes were compared to post-bath values. time course changes in ebf are presented in figure 1. ad and healthy subjects had very similar trends. none of the participants reported discomfort. no increased erythema or signs of irritation were observed in any of the participants. introduction methods results skin july 2018 volume 2 issue 4 copyright 2018 the national society for cutaneous medicine 221 table 1. outcome measures. percent differences in epidermal barrier function (ebf) (ph, hydration, and tewl) compared to control (no moisturizer). ph hydration tewl ad 15min 30min 60min 15min 30min 60min 15min 30min 60min cer 97.5% 100.5% 102.4% 442.9%* 394.4%* 413.2%* 493.5% 219.9%* 240.7% gly 106.1% 107.1%* 103.6% 828.3%* 722.9%* 684.3%* 379.4%* 179.0%* 218.5%* petr 96.3% 99.0% 97.5% 173.4% 315.7%* 382.8%* 181.7% 207.5%* 182.4%* aloe 88.2%* 94.1%* 92.3%* 328.2%* 256.9%* 269.7%* 246.2%* 202.0%* 184.8%* healthy 15min 30min 60min 15min 30min 60min 15min 30min 60min cer 99.2% 100.3% 98.1% 334.7%* 282.7%* 296.7%* 573.7%* 242.9%* 164.8% gly 110.4%* 108.3%* 100.7%* 815.2%* 695.1%* 639.4%* 455.0%* 206.1%* 171.3% petr 102.2% 99.1% 97.0% 96.8% 217.7%* 343.4%* 242.3%* 209.9%* 220.0%* aloe 91.2% 94.1% 91.1% 471.5%* 303.0%* 268.7%* 291.5%* 221.9%* 285.8%* ebf values were measured three-times to calculate average values. hydration and tewl were normalized to post-bath values. statistical analysis was performed using two-tailed-paired ttest. results were compared to post-bath values. differences in ebf were considered statistically significant when p-values were ≤ 0.05. * = p<0.05. ad, atopic dermatitis; tewl, transepidermal water loss; cer, ceramide-containing emollient cream; gly, 10% glycerin; petr, white petrolatum; aloe, 5% aloe vera extract. aloe is associated with the most significant decrease in absolute ph values throughout all time points in all subjects, nadir at 15minutes (88.2% in ad, 91.2% in healthy). in contrast, gly is associated with highest ph increase, values peaking at 15-minutes (106.1% in ad, 110.4% in healthy). there was no statistical difference in mean ph between cer and petr compared to control in both ad and healthy subjects at all time points measured. all four moisturizers increased hydration compared to control. gly led to the highest increase, peaking at 15-minutes for both ad (828.3%) and healthy (815.2%) subjects. petr led to initial hydration decrease with nadir at 15-minutes, followed by rapid recovery by 60-minutes. ad subjects had higher hydration following cer (442.9% 394.4%  413.2%) than healthy subjects (334.7%  282.7%  296.7%) throughout the entire study. to our surprise, all four moisturizers increased tewl compared to control throughout the entire study period. cer is associated with the highest initial tewl among all moisturizers, peaking at 15minutes (493.5% in ad, 573.7% in healthy), followed by rapid decrease by 60-minutes (240.7% in ad, 164.8% in healthy). petr is associated with the lowest initial tewl among all moisturizers at 15-minutes (246.2% in ad, 242.3% in healthy), followed by steady maintenance throughout the study. skin july 2018 volume 2 issue 4 copyright 2018 the national society for cutaneous medicine 222 figure 1. changes in epidermal barrier function (ebf) due to various moisturizers post-bathing. hydration and tewl values are normalized to baseline reading. percent post-bath of ph hydration, and tewl vs. time are graphed for ad and healthy participants. all 3 parameters were measured 3 times to obtain an average value with standard deviation. ph values for 3 healthy subjects were not obtained due to equipment malfunction. ph, ad ph, healthy skin july 2018 volume 2 issue 4 copyright 2018 the national society for cutaneous medicine 223 this study aimed to bring additional evidence to the “soak-and-smear” regimen by examining the effect of various types of moisturizers on ebf recovery post-bathing. we have previously demonstrated that bathing temporarily introduces moisture to the skin with a peak in hydration status immediately post-bathing in ad and healthy subjects [3]. in the current study, aloe is best at lowering sc ph. gly is best at introducing sc hydration. cer led to the most rapid tewl increase. petr is superior at limiting tewl at the initial phase. overall, moisturizers had an immediate effect on sc hydration status, whereas their effect on tewl is delayed, but slowly recovers toward control levels by 60-minutes. our study duration was limited by practical considerations of subject patience with participants sitting in the room during the entire study period. we did not follow the ebf measurements beyond 60-minutes post-bathing, which may explain that despite trending towards baseline, tewl status after moisturizer application was higher than control. the initial tewl increase within the first 60-minutes may be due to increased local water concentration after bathing and hydrating effects of the moisturizers. future studies are needed to examine the effect of repeated moisturizer use throughout the day following bathing or with repeated daily bathing, as recommended in real life practice. conflict of interest disclosures: dr. shi has equirty in dermveda and is a paid advisor for melno therapeutics and the national eczema association, as well as a paid preceptor for novartis. dr. sivamani is a scientific advisor for dermveda. the remainder of the authors have no relevant conflicts of interest. funding: none corresponding author: raja sivamani, md, ms, cat department of dermatology university of california, davis 3301 c street, suite 1400, sacramento, ca 95816 916-703-5145 (office) 916-734-4833 (fax) raja.sivamani.md@gmail.com references: 1 elias pm, schmuth m: abnormal skin barrier in the etiopathogenesis of atopic dermatitis. curr opin allergy clin immunol 2009; 9: 437-46. 2 gutman ab, kligman am, sciacca j, james wd: soak and smear: a standard technique revisited. arch dermatol 2005; 141: 1556-9. 3 shi vy, foolad n, ornelas jn, hassoun la, monico g, takeda n, saric s, prakash n, eichenfield lf, sivamani rk: comparing the effect of bleach and water baths on skin barrier function in atopic dermatitis: a split-body randomized controlled trial. br j dermatol 2016; 175: 212-4. discussion/conclusions introduction � many topical corticosteroids (cs) of differing potencies and formulations are available for treating psoriasis vulgaris � topical cs potency can be assessed by the vasoconstriction assay (mckenzie-stoughton), which is based on the blanching response of skin induced by topical cs application on healthy skin1 – this assay is recommended for topical cs potency ranking based on a correlation with clinical efficacy in psoriasis � a foam formulation of fixed-dose combination calcipotriol 50 µg/g (cal) and betamethasone 0.5 mg/g (as dipropionate; bd) has been developed as a treatment option for patients with psoriasis – clinical studies have demonstrated greater efficacy with cal/bd foam versus the gel and ointment formulations 2-6 � the objective of this study was to compare the cs potency of bd in cal/bd foam with existing cs-containing topical products methods patients � the study enrolled healthy, non-smoking volunteers aged 18–50 years – all subjects were required to demonstrate adequate vasoconstriction prior to the study, defined as a visual skin blanching score of at least one unit following non-occlusive bd 0.05% ointment application for 4–6 hours � subjects were excluded if they received systemic treatments or any medications that could interfere with the blanching reaction within 2 weeks, or had used topical cs on the test sites within 4 weeks prior to enrolment study design � this was a phase i, single-centre, investigator-blinded, vehicle-controlled, intra-individual comparison study (nct02973776) � each volunteer received a single application, under non-occlusive conditions of: cal/bd foam, clobetasol propionate 0.05% cream (cp; very potent), bd 0.05% ointment (potent), mometasone furoate 0.1% cream (mf; potent), hydrocortisone-17-butyrate 0.1% ointment (hb; moderately potent) and foam vehicle to six circular test sites (each 2.2 cm in diameter) on the anterior forearms � after 16 hours of exposure, any remaining product was removed study objectives and assessments � the primary objective was to compare the vasoconstriction potential of cal/bd foam with the other treatments using the human skin blanching test (mckenzie-stoughton vasoconstriction assay)1 � skin blanching for each treatment was assessed 2 hours after the 16-hour application period by two independent, trained observers – visual assessment of skin blanching was scored on a 9-point scale from 0–4 (0 = no change, 4 = maximal blanching; half-point scores were used for intermediate changes) � local tolerability was assessed at the same time as skin blanching and at follow-up; safety was assessed throughout the study by evaluation of adverse events (aes) statistical analysis � the mean of the two individual skin blanching visual scores were calculated for each treatment, and non-parametric tests were performed. kruskal-wallis test for the overall effect, and wilcoxon signed rank test for the pairwise comparisons (cal/bd foam vs other treatments) results patients � a total of 36 healthy volunteers were randomized and analysed (table 1) assessment of skin blanching � all active treatments resulted in greater skin blanching compared with foam vehicle (figure 1; table 2) � skin blanching with cal/bd foam was significantly lower than with cp cream (p<0.001), similar to bd ointment and mf cream, and significantly higher than hb ointment and foam vehicle (p<0.001 for both) [figure 1; table 2] � no aes were reported, and all subjects had a local tolerability score of 0 (ie, no reaction) vasoconstrictor potency of fixed combination calcipotriol plus betamethasone dipropionate foam versus other corticosteroid psoriasis treatments catherine queille-roussel,1 jakob nielsen2 1centre de pharmacologie clinique appliquée à la dermatologie, nice, france; 2leo pharma a/s, ballerup, denmark p1908 poster presented at the 26th eadv congress, geneva, switzerland, 13–17 september 2017 � understanding topical cs potency is important to ensure the appropriate use of treatments for psoriasis: – the degree of skin blanching is used as a measure of the inherent potency of a cs, and its ability to diffuse into the skin � this study showed that, consistent with cs potency classifications, the steroid potency of cal/bd foam was similar to bd ointment and mf cream, significantly stronger than that of hb ointment, but weaker than that of very potent cp cream � these findings expand on those from a previously reported phase i study, which showed that cal/bd foam was a more potent formulation than cal/bd ointment7 conclusions acknowledgements � this study was sponsored by leo pharma. medical writing support was provided by andrew jones, phd, from mudskipper business limited, funded by leo pharma references 1. mckenzie aw & stoughton rb. arch dermatol 1962;86:608–10 2. leonardi c et al. j drugs dermatol 2015;14:1468–77 3. koo j et al. j dermatolog treat 2016;27:120–7 4. paul c et al. j eur acad dermatol venereol 2017;31:119–26 5. queille-roussel c et al. clin drug investig 2015;35:239–45 6. stein gl et al. j drugs dermatol 2016;15:951–7 7. queille-roussel c et al. j eur acad dermatol venereol 2016;30:1951–6 table 2. skin blanching scores by treatment, assessed 2 hours after 16 hours of treatment application treatment mean (sd) median (range) p value (v cal/bd foam) cal/bd foam 1.93 (0.56) 2.00 (0.75–3.00) – cp cream 3.09 (0.55) 3.00 (1.75–4.00) <0.001 bd ointment 1.85 (0.59) 1.75 (0.75–3.00) 0.30 mf cream 2.11 (0.59) 2.00 (1.00–3.75) 0.22 hb ointment 1.40 (0.66) 1.25 (0.50–3.00) <0.001 foam vehicle 0.06 (0.13) 0 (0–0.50) <0.001 sd, standard deviation table 2. baseline demographic and characteristics of randomized subjects subjects (n=36) median age (range), years 34.5 (19–50) males:females, n (%) 14:22 (38.9:61.1) race, n (%) white 36 (100.0) fitzpatrick skin type, n (%) ii 5 (13.9) iii 30 (83.3) iv 1 (2.8) median bmi (range), kg/m2 22.9 (16.2–34.5) bmi, body mass index figure 1. box plot showing visual assessment of skin blanching 2 hours after 16 hours of treatment application the horizontal line represents the median, and the circle represents the mean; the box represents the interquartile range (iqr), and the whiskers represent the range within 1.5 x iqr cal/bd foam cp cream bd ointment mf cream hb ointment vehicle sk in b la nc hi ng 2 h ou rs a ft er pr od uc t r em ov al 4 3 2 1 0 pcg-workstation-2 sticky note marked set by pcg-workstation-2 pcg-workstation-2 sticky note marked set by pcg-workstation-2 pcg-workstation-2 sticky note marked set by pcg-workstation-2 pcg-workstation-2 sticky note marked set by pcg-workstation-2 pcg-workstation-2 sticky note marked set by pcg-workstation-2 pcg-workstation-2 sticky note marked set by pcg-workstation-2 pcg-workstation-2 sticky note marked set by pcg-workstation-2 pcg-workstation-2 sticky note marked set by pcg-workstation-2 pcg-workstation-2 sticky note marked set by pcg-workstation-2 pcg-workstation-2 sticky note marked set by pcg-workstation-2 pcg-workstation-2 sticky note marked set by pcg-workstation-2 pcg-workstation-2 sticky note marked set by pcg-workstation-2 deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, in moderate to severe plaque psoriasis: efficacy by baseline demographic and disease characteristics in the phase 3 poetyk pso-1 and pso-2 trials melinda gooderham,1 lynda spelman,2 shinichi imafuku,3 marco romanelli,4 joseph f. merola,5 april w. armstrong,6 elizabeth colston,7 subhashis banerjee,7 thomas scharnitz,7 andrew blauvelt8 1skin centre for dermatology, queen’s university, and probity medical research, peterborough, on, canada; 2veracity clinical research, brisbane, qld, australia; 3fukuoka university hospital, fukuoka, japan; 4university of pisa, pisa, italy; 5brigham and women's hospital, brigham dermatology associates, and harvard medical school, boston, ma, usa; 6university of southern california, los angeles, ca, usa; 7bristol myers squibb, princeton, nj, usa; 8oregon medical research center, portland, or, usa introduction • deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 (tyk2) inhibitor, is approved in the us, eu, and other countries for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy1,2 • deucravacitinib has a unique mechanism of action distinct from janus kinase (jak) inhibitors3,4 (figure 1) — binds to the tyk2 regulatory domain and inhibits tyk2 via an allosteric mechanism3 — inhibits tyk2-mediated signaling of cytokines involved in psoriasis pathogenesis (interleukin-23 and type i interferons)3 • deucravacitinib was significantly more efficacious than placebo or apremilast and was well tolerated in patients with moderate to severe plaque psoriasis in the 52-week, phase 3 poetyk pso-1 (nct03624127) and poetyk pso-2 (nct03611751) trials5,6 objective • the current pooled analyses of the poetyk pso-1 and pso-2 trials at weeks 24 and 52 were performed to evaluate the efficacy of deucravacitinib across baseline patient demographics and disease characteristics methods study designs • the study designs for poetyk pso-1 and pso-2 are summarized in figure 2 • key eligibility criteria included the following: — age ≥18 years — diagnosis of moderate to severe plaque psoriasis • baseline psoriasis area and severity index (pasi) ≥12, static physician’s global assessment (spga) ≥3, and body surface area (bsa) involvement ≥10% • patient randomization was stratified by geographic region, body weight, and prior biologic use • in poetyk pso-1, 97.8% and 97.2% of patients completed 24 weeks of deucravacitinib and apremilast treatment, respectively; in poetyk pso-2, 96.3% and 95.9% of patients completed 24 weeks of deucravacitinib and apremilast treatment, respectively • in poetyk pso-1, 89.5% of patients completed 52 weeks of deucravacitinib treatment • all patients were eligible for a long-term extension trial after 52 weeks of treatment figure 2. poetyk pso-1 and pso-2 study designs poetyk pso-1 (n = 666) deucravacitinib 6 mg qdplacebo (n = 166) deucravacitinib 6 mg qd apremilast 30 mg bid 1 :2 :1 r an d o m iz at io n 52weeks deucravacitinib 6 mg qd (n = 332) 16 24 ≥pasi 50 apremilast 30 mg bida (n = 168) primary endpoint 0 <pasi 50 poetyk pso-2 (n = 1020) placebo (n =255) deucravacitinib 6 mg qd (n = 511) deucravacitinib 6 mg qd deucravacitinib 6 mg qd<pasi 75 deucravacitinib 6 mg qd deucravacitinib 6 mg qd apremilast 30 mg bida (n=254) ≥pasi 75 52weeks 1:1 placebob deucravacitinib 6 mg qd 16 24 <pasi 75 primary endpoint 1 :2 :1 r an d o m iz at io n placebob deucravacitinib 6 mg qd 0 ≥pasi 75 coprimary endpoints: pasi 75 and spga 0/1 for deucravacitinib vs placebo at week 16 from armstrong aw, et al. deucravacitinib versus placebo and apremilast in moderate to severe plaque psoriasis: efficacy and safety results from the 52-week, randomized, double-blinded, placebo-controlled phase 3 poetyk pso-1 trial. j am acad dermatol. 2023;8:29-39. https://www.jaad.org/article/s0190-9622(22)02256-3/pdf. this work is licensed under a creative commons attribution license (cc by-nc-nd 4.0). https://creativecommons.org/licenses/ by-nc-nd/4.0/. from strober b, et al. deucravacitinib versus placebo and apremilast in moderate to severe plaque psoriasis: efficacy and safety results from the 52-week, randomized, double-blinded, phase 3 program for evaluation of tyk2 inhibitor psoriasis second trial. j am acad dermatol. 2023;88:40-51. https://www.jaad.org/article/s0190-9622(22)02643-3/pdf. this work is licensed under a creative commons attribution license (cc by-nc-nd 4.0). https://creativecommons.org/ licenses/by-nc-nd/4.0/. aapremilast was titrated from 10 mg qd to 30 mg bid over the first 5 days of dosing. bupon relapse (≥50% loss of week 24 pasi percentage improvement from baseline), patients were to be switched to deucravacitinib 6 mg qd. bid, twice daily; pasi, psoriasis area and severity index; pasi 50, ≥50% reduction from baseline in pasi; pasi 75, ≥75% reduction from baseline in pasi; qd, once daily; spga 0/1, static physician's global assessment score of 0 (clear) or 1 (almost clear) with a ≥2-point improvement from baseline. assessments and statistical analyses • data from subgroups with the following baseline patient demographics and disease characteristics in poetyk pso-1 and pso-2 were pooled and analyzed for the coprimary endpoints (≥75% reduction from baseline in pasi [pasi 75] and spga score of 0 [clear] and 1 [almost clear] with a ≥2-point improvement from baseline [spga 0/1]) and ≥90% reduction from baseline in pasi (pasi 90) vs apremilast at week 24 — baseline patient demographics: age (<40 y, 40-65 y, ≥65 y); weight (<90 kg, ≥90 kg, body weight deciles); body mass index (bmi; <25 kg/m2, 25-<30 kg/m2, 30-<35 kg/m2, ≥35 kg/m2); sex; race (white, asian) • due to a low number of patients in these subgroups, black or african american or other races were not analyzed — baseline disease characteristics: pasi score (≤20, >20); spga score (3 [moderate], 4 [severe]); bsa involvement (10-20%, >20%) • in patients who received continuous deucravacitinib treatment from day 1, data were also analyzed at week 52 (poetyk pso-1) • differences between treatment groups were calculated using a stratified cochran-mantel-haenszel test • missing data were imputed using nonresponder imputation results patients • baseline patient demographics and disease characteristics were largely similar across treatment groups in both trials (table 1) table 1. baseline patient demographics and disease characteristics pooled poetyk pso-1 and pso-2 parameter placebo (n = 421) deucravacitinib (n = 843) apremilast (n = 422) total (n = 1686) age, mean (sd), y 47.5 (13.7) 46.5 (13.5) 45.7 (12.8) 46.6 (13.4) <65 y, n (%) 370 (87.9) 763 (90.5) 384 (91.0) 1517 (90.0) ≥65 y, n (%) 51 (12.1) 80 (9.5) 38 (9.0) 169 (10.0) weight, mean (sd), kg 90.6 (21.1) 90.6 (21.9) 91.1 (22.0) 90.7 (21.7) female, n (%) 127 (30.2) 277 (32.9) 155 (36.7) 559 (33.2) race, n (%) white 360 (85.5) 741 (87.9) 368 (87.2) 1469 (87.1) asian 42 (10.0) 83 (9.8) 40 (9.5) 165 (9.8) black or african american 12 (2.9) 10 (1.2) 10 (2.4) 32 (1.9) other 7 (1.7) 9 (1.1) 4 (0.5) 20 (1.2) disease duration, mean (sd), y 18.9 (12.9) 18.6 (12.7) 18.5 (12.1) 18.6 (12.6) prior systemic therapy, n (%) biologic 146 (34.7) 295 (35.0) 145 (34.4) 586 (34.8) no prior systemic therapy 173 (41.1) 369 (43.8) 173 (41.0) 715 (42.4) pasi score, mean (sd) 20.9 (8.6) 21.1 (8.0) 21.6 (8.6) 21.2 (8.3) ≤20, n (%) 254 (60.3) 475 (56.3) 241 (57.1) 970 (57.5) >20, n (%) 167 (39.7) 368 (43.7) 181 (42.9) 716 (42.5) spga score, n (%) 3 (moderate) 345 (81.9) 665 (78.9) 335 (79.4) 1345 (79.8) 4 (severe) 75 (17.8) 178 (21.1) 87 (20.6) 340 (20.2) bsa involvement, mean (sd), % 25.3 (16.1) 26.4 (15.8) 27.6 (16.4) 26.4 (16.0) bsa ≤20%, n (%) 226 (53.7) 421 (49.9) 200 (47.4) 847 (50.2) bsa >20%, n (%) 195 (46.3) 422 (50.1) 222 (52.6) 839 (49.8) bsa, body surface area; pasi, psoriasis area and severity index; sd, standard deviation; spga, static physician’s global assessment. efficacy • analyses of pooled data from poetyk pso-1 and pso-2 using pasi 75 (figure 3; figure 4), pasi 90 (figure 5; figure 6), and spga 0/1 (figure 7; figure 8) demonstrated a consistent treatment benefit of deucravacitinib (n = 843) vs apremilast (n = 422) across multiple baseline patient demographics and disease characteristics at week 24 — deucravacitinib also demonstrated a consistent treatment benefit vs placebo and apremilast across these characteristics at week 167,8 figure 3. pasi 75 outcomes by baseline demographics (week 24; pooled poetyk pso-1 + pso-2) -20 -10 0 10 20 30 40 50 60 70 body weight 10th decile (heaviest) body weight 9th decile body weight 8th decile body weight 7th decile body weight 6th decile body weight 5th decile body weight 4th decile body weight 3rd decile body weight 2nd decile body weight 1st decile (lightest) weight ≥90 kg weight <90 kg age ≥65 y age 40-65 y age <40 y difference (95% ci) patients, n/n (%) deucravacitinib apremilast difference vs apremilast (95% ci) asian white female male bmi ≥35 kg/m2 bmi 30-<35 kg/m2 bmi 25-<30 kg/m2 bmi <25 kg/m2 19.0 (1.0, 37.0) 15.1 (-2.9, 33.1) 11.9 (-6.8, 30.6) 28.4 (12.0, 44.8) 44.3 (27.0, 61.6) 26.6 (8.9, 44.3) 32.0 (14.2, 49.7) 19.3 (2.1, 36.4) 27.2 (8.9, 45.5) 24.7 (7.1, 42.2) 23.8 (15.8, 31.9) 26.0 (18.1, 33.8) 2.9 (-15.8, 21.6) 20.3 (12.6, 27.9) 38.6 (29.4, 47.8) 37.3 (19.8, 54.8) 24.2 (18.1, 30.2) 25.3 (15.8, 34.8) 25.6 (18.6, 32.5) 12.3 (0.0, 24.7) 28.7 (17.6, 39.8) 29.9 (20.0, 39.9) 28.0 (15.8, 40.1) 14/40 (35.0) 13/42 (31.0) 15/39 (38.5) 13/49 (26.5) 13/41 (31.7) 15/43 (34.9) 13/39 (33.3) 25/51 (49.0) 17/40 (42.5) 22/38 (57.9) 64/203 (31.5) 96/219 (43.8) 23/38 (60.5) 93/236 (39.4) 44/148 (29.7) 12/40 (30.0) 143/368 (38.9) 70/155 (45.2) 90/267 (33.7) 39/97 (40.2) 31/102 (30.4) 46/131 (35.1) 43/91 (47.3) 48/86 (55.8) 38/82 (46.3) 43/86 (50.0) 45/82 (54.9) 58/78 (74.4) 51/83 (61.4) 59/90 (65.6) 54/79 (68.4) 54/78 (69.2) 76/92 (82.6) 221/399 (55.4) 305/437 (69.8) 50/77 (64.9) 292/490 (59.6) 184/269 (68.4) 56/83 (67.5) 462/734 (62.9) 193/274 (70.4) 333/562 (59.3) 92/174 (52.9) 128/217 (59.0) 178/275 (65.1) 127/169 (75.1) apremilast better deucravacitinib better bmi, body mass index; ci, confidence interval; pasi 75, ≥75% reduction from baseline in psoriasis area and severity index. figure 4. pasi 75 outcomes by baseline disease characteristics (week 24; pooled poetyk pso-1 + pso-2) apremilast better deucravacitinib better -20 -10 0 10 20 30 40 50 60 70 difference vs apremilast (95% ci) bsa >20% bsa 10-20% spga score, 4 (severe) spga score, 3 (moderate) pasi >20 pasi ≤20 23.2 (15.3, 31.2) 26.7 (18.6, 34.9) 23.6 (11.3, 36.0) 25.2 (18.8, 31.6) 27.3 (18.7, 35.9) 23.2 (15.6, 30.7) 86/222 (38.7) 74/200 (37.0) 30/87 (34.5) 130/335 (38.8) 67/181 (37.0) 93/241 (38.6) 260/417 (62.4) 266/419 (63.5) 105/177 (59.3) 421/659 (63.9) 236/365 (64.7) 290/471 (61.6) difference (95% ci) patients, n/n (%) deucravacitinib apremilast bsa, body surface area; ci, confidence interval; pasi, psoriasis area and severity index; pasi 75, ≥75% reduction from baseline in pasi; spga, static physician’s global assessment. figure 5. pasi 90 outcomes by baseline demographics (week 24; pooled poetyk pso-1 + pso-2) -20 -10 0 10 20 30 40 50 body weight 10th decile (heaviest) body weight 9th decile body weight 8th decile body weight 7th decile body weight 6th decile body weight 5th decile body weight 4th decile body weight 3rd decile body weight 2nd decile body weight 1st decile (lightest) weight ≥90 kg weight <90 kg age ≥65 y age 40-65 y age <40 y difference (95% ci) patients, n/n (%) deucravacitinib apremilast difference vs apremilast (95% ci) asian white female male bmi ≥35 kg/m2 bmi 30-<35 kg/m2 bmi 25-<30 kg/m2 bmi <25 kg/m2 9.9 (-4.5, 24.2) 7.5 (-7.3, 22.2) 4.3 (-11.7, 20.2) 13.9 (0.1, 27.6) 28.6 (13.3, 43.9) 12.7 (-2.7, 28.0) 21.1 (5.8, 36.3) 23.0 (7.0, 39.1) 12.6 (-5.7, 30.8) 21.9 (3.5, 40.2) 12.5 (5.9, 19.1) 18.6 (11.2, 26.0) 14.8 (-3.4, 32.9) 9.9 (3.1, 16.7) 26.1 (17.8, 34.3) 30.5 (14.2, 46.8) 14.4 (9.0, 19.9) 15.9 (6.6, 25.1) 16.5 (10.7, 22.3) 2.6 (-7.9, 13.2) 20.2 (11.2, 29.1) 18.3 (9.5, 27.1) 22.2 (10.2, 34.1) 23/86 (26.7) 20/82 (24.4) 21/86 (24.4) 23/82 (28.0) 32/78 (41.0) 26/83 (31.3) 33/90 (36.7) 37/79 (46.8) 35/78 (44.9) 54/92 (58.7) 111/399 (27.8) 193/437 (44.2) 32/77 (41.6) 160/490 (32.7) 112/269 (41.6) 42/83 (50.6) 259/734 (35.3) 123/274 (44.9) 181/562 (32.2) 44/174 (25.3) 71/217 (32.7) 103/275 (37.5) 86/169 (50.9) 6/40 (15.0) 7/42 (16.7) 8/39 (20.5) 7/49 (14.3) 6/41 (14.6) 8/43 (18.6) 6/39 (15.4) 12/51 (23.5) 13/40 (32.5) 14/38 (36.8) 31/203 (15.3) 56/219 (25.6) 10/38 (26.3) 54/236 (22.9) 23/148 (15.5) 8/40 (20.0) 77/368 (20.9) 45/155 (29.0) 42/267 (15.7) 22/97 (22.7) 13/102 (12.7) 25/131 (19.1) 26/91 (28.6) apremilast better deucravacitinib better bmi, body mass index; ci, confidence interval; pasi 90, ≥90% reduction from baseline in psoriasis area and severity index. figure 6. pasi 90 outcomes by baseline disease characteristics (week 24; pooled poetyk pso-1 + pso-2) apremilast better deucravacitinib better -20 -10 0 10 20 30 40 50 difference vs apremilast (95% ci) bsa >20% bsa 10-20% spga score, 4 (severe) spga score, 3 (moderate) pasi >20 pasi ≤20 18.2 (11.1, 25.4) 13.2 (6.0, 20.3) 17.5 (6.5 , 28.5) 15.0 (9.4 , 20.7) 22.0 (14.1, 29.8) 10.8 (4.3, 17.4) 47/222 (21.2) 40/200 (20.0) 17/87 (19.5) 70/335 (20.9) 38/181 (21.0) 49/241 (20.3) 166/417 (39.8) 138/419 (32.9) 68/177 (38.4) 236/659 (35.8) 158/365 (43.3) 146/471 (31.0) difference (95% ci) patients, n/n (%) deucravacitinib apremilast bsa, body surface area; ci, confidence interval; pasi, psoriasis area and severity index; pasi 90, ≥90% reduction from baseline in pasi; spga, static physician’s global assessment. figure 7. spga 0/1 outcomes by baseline demographics (week 24; pooled poetyk pso-1 + pso-2) -20 -10 0 10 20 30 40 6050 body weight 10th decile (heaviest) body weight 9th decile body weight 8th decile body weight 7th decile body weight 6th decile body weight 5th decile body weight 4th decile body weight 3rd decile body weight 2nd decile body weight 1st decile (lightest) weight ≥90 kg weight <90 kg age ≥65 y age 40-65 y age <40 y difference (95% ci) patients, n/n (%) deucravacitinib apremilast difference vs apremilast (95% ci) asian white female male bmi ≥35 kg/m2 bmi 30-<35 kg/m2 bmi 25-<30 kg/m2 bmi <25 kg/m2 42/86 (48.8) 35/82 (42.7) 33/86 (38.4) 36/82 (43.9) 48/78 (61.5) 44/83 (53.0) 51/90 (56.7) 47/79 (59.5) 42/78 (53.8) 68/92 (73.9) 183/399 (45.9) 263/437 (60.2) 42/77 (54.5) 248/490 (50.6) 156/269 (58.0) 49/83 (59.0) 391/734 (53.3) 167/274 (60.9) 279/562 (49.6) 79/174 (45.4) 108/217 (49.8) 152/275 (55.3) 107/169 (63.3) 9/40 (22.5) 11/42 (26.2) 12/39 (30.8) 12/49 (24.5) 13/41 (31.7) 11/43 (25.6) 10/39 (25.6) 19/51 (37.3) 14/40 (35.0) 16/38 (42.1) 52/203 (25.6) 75/219 (34.2) 15/38 (39.5) 79/236 (33.5) 33/148 (22.3) 12/40 (30.0) 111/368 (30.2) 61/155 (39.4) 66/267 (24.7) 31/97 (32.0) 27/102 (26.5) 38/131 (29.0) 31/91 (34.1) 24.7 (8.1, 41.3) 16.4 (-0.8, 33.5) 7.3 (-10.6, 25.3) 19.5 (3.5, 35.6) 31.5 (3.5, 49.6) 27.6 (10.7, 44.5) 31.1 (13.8, 48.3) 22.4 (5.3, 39.6) 19.3 (1.0, 37.7) 31.8 (13.6, 50.0) 20.2 (12.5, 27.9) 25.9 (18.2, 33.7) 14.5 (-4.8, 33.8) 17.2 (9.7, 24.7) 35.6 (26.8, 44.5) 28.8 (11.3, 46.4) 23.2 (17.3, 29.1) 21.6 (12.0, 31.2) 24.9 (18.3, 31.6) 13.1 (1.2, 25.0) 23.5 (12.7, 34.2) 26.3 (16.5, 36.0) 29.3 (17.1, 41.5) apremilast better deucravacitinib better bmi, body mass index; ci, confidence interval; spga 0/1, static physician’s global assessment score of 0 (clear) or 1 (almost clear) with a ≥2-point improvement from baseline. figure 8. spga 0/1 outcomes by baseline disease characteristics (week 24; pooled poetyk pso-1 + pso-2) apremilast better deucravacitinib better -20 -10 0 10 20 30 40 6050 difference vs apremilast (95% ci) bsa >20% bsa 10-20% spga score, 4 (severe) spga score, 3 (moderate) pasi >20 pasi ≤20 25.3 (17.7, 32.9) 21.0 (13.0, 29.1) 24.7 (13.2, 36.3) 22.8 (16.6, 29.1) 25.7 (17.4, 34.0) 21.3 (13.8, 28.7) 63/222 (28.4) 64/200 (32.0) 20/87 (23.0) 107/335 (31.9) 49/181 (27.1) 78/241 (32.4) 225/417 (54.0) 221/419 (52.7) 86/177 (48.6) 360/659 (54.6) 194/365 (53.2) 252/471 (53.5) difference (95% ci) patients, n/n (%) deucravacitinib apremilast bsa, body surface area; ci, confidence interval; pasi, psoriasis area and severity index; spga, static physician’s global assessment; spga 0/1, spga score of 0 (clear) or 1 (almost clear) with a ≥2-point improvement from baseline. • efficacy was observed through week 52 in patients who received continuous deucravacitinib treatment in poetyk pso-1 (n = 332), regardless of baseline patient demographics or disease severity (table 2; table 3) table 2. week 52 outcomes by baseline demographics (poetyk pso-1) pasi 75 pasi 90 spga 0/1 parameter deucravacitinib, n/n (%) (n = 332) deucravacitinib, n/n (%) (n = 332) deucravacitinib, n/n (%) (n = 332) age, y <40 71/109 (65.1) 44/109 (40.4) 59/109 (54.1) 40-65 125/197 (63.5) 88/197 (44.7) 101/197 (51.3) ≥65 20/26 (76.9) 14/26 (53.8) 15/26 (57.7) weight, kg <90 146/200 (73.0) 103/200 (51.5) 121/200 (60.5) ≥90 70/132 (53.0) 43/132 (32.6) 54/132 (40.9) body weight categories, decile 1st decile (lightest) 29/39 (74.4) 26/39 (66.7) 28/39 (71.8) 2nd decile 31/41 (75.6) 25/41 (61.0) 23/41 (56.1) 3rd decile 28/38 (73.7) 19/38 (50.0) 24/38 (63.2) 4th decile 31/41 (75.6) 19/41 (46.3) 22/41 (53.7) 5th decile 21/34 (61.8) 10/34 (29.4) 19/34 (55.9) 6th decile 20/25 (80.0) 14/25 (56.0) 19/25 (76.0) 7th decile 14/24 (58.3) 8/24 (33.3) 12/24 (50.0) 8th decile 14/32 (43.8) 10/32 (31.3) 9/32 (28.1) 9th decile 12/27 (44.4) 6/27 (22.2) 6/27 (22.2) 10th decile (heaviest) 16/31 (51.6) 9/31 (29.0) 13/31 (41.9) bmi, kg/m2 <25 55/78 (70.5) 45/78 (57.7) 46/78 (59.0) 25-<30 89/123 (72.4) 56/123 (45.5) 74/123 (60.2) 30-<35 40/69 (58.0) 25/69 (36.2) 31/69 (44.9) ≥35 32/62 (51.6) 20/62 (32.3) 24/62 (38.7) sex male 139/230 (60.4) 82/230 (35.7) 105/230 (45.7) female 77/102 (75.5) 64/102 (62.7) 70/102 (68.6) race white 168/267 (62.9) 115/267 (43.1) 141/267 (52.8) asian 45/59 (76.3) 31/59 (52.5) 33/59 (55.9) bmi, body mass index; pasi 75/90, ≥75%/≥90% reduction from baseline in psoriasis area and severity index; spga 0/1, static physician’s global assessment score of 0 (clear) or 1 (almost clear) with a ≥2-point improvement from baseline. table 3. week 52 outcomes by baseline disease characteristics (poetyk pso-1) pasi 75 pasi 90 spga 0/1 parameter deucravacitinib, n/n (%) (n = 332) deucravacitinib, n/n (%) (n = 332) deucravacitinib, n/n (%) (n = 332) pasi score ≤20 109/177 (61.6) 69/177 (39.0) 85/177 (48.0) >20 107/155 (69.0) 77/155 (49.7) 90/155 (58.1) spga score 3 (moderate) 166/257 (64.6) 107/257 (41.6) 137/257 (53.3) 4 (severe) 50/75 (66.7) 39/75 (52.0) 38/75 (50.7) bsa involvement, % 10-20% 102/162 (63.0) 61/162 (37.7) 82/162 (50.6) >20% 114/170 (67.1) 85/170 (50.0) 93/170 (54.7) bsa, body surface area; pasi, psoriasis area and severity index; pasi 75/90, ≥75%/≥90% reduction from baseline in pasi; spga, static physician’s global assessment; spga 0/1, spga score of 0 (clear) or 1 (almost clear) with a ≥2-point improvement from baseline. conclusions • deucravacitinib is efficacious in adults with moderate to severe plaque psoriasis, regardless of baseline patient demographics and disease characteristics — deucravacitinib was more efficacious than apremilast across baseline subgroups at week 24 in the pooled analysis of poetyk pso-1 and pso-2 — continuous deucravacitinib treatment was efficacious across baseline subgroups at week 52 in poetyk pso-1 • these findings further support deucravacitinib, a once-daily oral drug, as an efficacious therapeutic option for adults with moderate to severe plaque psoriasis regardless of baseline patient demographics or disease characteristics references 1. sotyktu™ (deucravacitinib) [package insert]. princeton, nj; bristol-myers squibb company; september 2022. 2. sotyktu (deucravacitinib) [summary of product characteristics]. dublin, ireland: bristol-myers squibb pharma eeig; march 2023. 3. burke jr, et al. sci transl med. 2019;11:eaaw1736. 4. wrobleski st, et al. j med chem. 2019;62:8973-8995. 5. armstrong aw, et al. j am acad dermatol. 2023;88:29-39. 6. strober b, et al. j am acad dermatol. 2023;88:40-51. 7. gooderham m, et al. presented at 30th eadv congress; september 29–october 2, 2021. 8. merola jf, et al. presented at 30th eadv congress; september 29–october 2, 2021. acknowledgments • this study was sponsored by bristol myers squibb • writing and editorial assistance was provided by jieming fang, md, of peloton advantage, llc, an open health company, parsippany, nj, usa, funded by bristol myers squibb disclosures • mg: advisory board, principal investigator, and lecture fees: abbvie, galderma, leo pharma, pfizer, and regeneron; advisory board and lecture fees: actelion; principal investigator and consulting fees: akros pharma; advisory board, principal investigator, lecture fees, and consulting fees: amgen, boehringer ingelheim, celgene, eli lilly, janssen, novartis, sanofi genzyme, and valeant; principal investigator: arcutis, bristol myers squibb, dermira, glaxosmithkline, medimmune, merck, roche laboratories, and ucb; principal investigator and lecture fees: glenmark • ls: consultant, paid investigator, and/or speaker: abbvie, amgen, anacor, ascend, astellas, astrazeneca, blaze bioscience, boehringer ingelheim, botanix, bristol myers squibb, celgene, dermira, eli lilly, galderma, genentech, glaxosmithkline, hexima, janssen, leo pharma, mayne pharma, medimmune, merck, merck-serono, novartis, otsuka, pfizer, phosphagenics, photon md, regeneron, roche, samumed, sanofi genzyme, shr pharmacy, sun pharma anz, trius, ucb, and zai lab • si: grants and personal fees: abbvie, eisai, janssen, kyowa kirin, leo pharma, maruho, sun pharma, taiho yakuhin, tanabe mitsubishi, and torii yakuhin; personal fees: amgen (celgene), boehringer ingelheim, bristol myers squibb, daiichi sankyo, eli lilly, glaxosmithkline, novartis, and ucb • mr: nothing to disclose • jfm: consultant and/or investigator: abbvie, amgen, biogen, bristol myers squibb, dermavant, eli lilly, janssen, leo pharma, novartis, pfizer, regeneron, sanofi, sun pharma, and ucb • awa: grants and personal fees: abbvie, bristol myers squibb, eli lilly, janssen, leo pharma, and novartis; personal fees: boehringer ingelheim/parexel, celgene, dermavant, genentech, glaxosmithkline, menlo therapeutics, merck, modernizing medicine, ortho dermatologics, pfizer, regeneron, sanofi genzyme, science 37, sun pharma, and valeant; grants: dermira, kyowa kirin, and ucb, outside the submitted work • ec, sb, and ts: employees and shareholders: bristol myers squibb • ab: speaker (with honoraria): abbvie, arcutis, bristol myers squibb, eli lilly, pfizer, regeneron, sanofi, and ucb; scientific adviser (with honoraria): abbvie, abcentra, affibody, aligos, almirall, alumis, amgen, anaptysbio, arcutis, arena, aslan, athenex, bluefin biomedicine, boehringer ingelheim, bristol myers squibb, cara therapeutics, dermavant, ecor1, eli lilly, escient, evelo, evommune, forte, galderma, highlightii pharma, incyte, innoventbio, janssen, landos, leo pharma, merck, novartis, pfizer, rapt, regeneron, sanofi genzyme, spherix global insights, sun pharma, tll pharmaceutical, trialspark, ucb, vibliome, and xencor; clinical study investigator (institution has received clinical study funds): abbvie, acelyrin, almirall, amgen, arcutis, athenex, boehringer ingelheim, bristol myers squibb, concert, dermavant, eli lilly, evelo, evommune, galderma, incyte, janssen, leo pharma, merck, novartis, pfizer, regeneron, sun pharma, and ucb presented at the fall clinical dermatology conference for pas & nps®; june 9-11, 2023; orlando, fl this is an encore of the 2023 aad poster email: mgooderham@centrefordermatology.com copies of this poster are for personal use only and may not be reproduced without written permission of the authors. figure 1. mechanism of action of deucravacitinib deucravacitinib (allosteric inhibitor class) unique tyk2 regulatory domain catalytic domain (highly conserved across jak family) atp-binding active site (approved jak inhibitor class) tyk2 selectivity in cells3,4: • ≥100-fold greater selectivity for tyk2 vs jak1 and jak3 • ≥2000-fold greater selectivity for tyk2 vs jak2 atp, adenosine 5′-triphosphate; jak, janus kinase; tyk2, tyrosine kinase 2. https://creativecommons.org/licenses/by-nc-nd/4.0/ https://creativecommons.org/licenses/by-nc-nd/4.0/ https://creativecommons.org/licenses/by-nc-nd/4.0/ https://creativecommons.org/licenses/by-nc-nd/4.0/ mailto:mgooderham@centrefordermatology.com 23-1156c fcpanp eff by bc ds [23tyk2130] 23-1156c fcpanp eff by bc ds [23tyk2130]_brk skin march 2018 volume 2 issue 2 copyright 2018 the national society for cutaneous medicine 135 brief articles distinguishing features: staphylococcal scalded skin syndrome vs. toxic epidermal necrolysis hannah badon bs a , joy king md b , robert t. brodell md b,c , adam byrd md d a university of mississippi medical center, jackson, ms b department of pathology, university of mississippi medical center, jackson, ms c department of dermatology, university of mississippi medical center, jackson, ms staphylococcal scalded skin syndrome (ssss) and toxic epidermal necrolysis (ten) share many clinical features. both demonstrate widespread blistering, positive nikolsky sign and tender skin. in fact, when ten was first described in 1956, it was reported to be “an eruption resembling scalding of the skin.” 1 there are many differences, however. staphylococcal scalded skin syndrome is usually seen in young children and infants, though it can be seen in adults with renal failure. the mortality of ten (25%-35%) 2 is generally higher than ssss (4% in children and infants). however, due to comorbid conditions, the mortality of ssss in adults can be as high as 60%. 3 most importantly, these conditions have entirely different pathophysiologic mechanisms. distinguishing between these two conditions with similar clinical features early in the course of the process is important since the correct diagnosis impacts both the prognosis and treatment approach. there are notable differences in the pathophysiologic basis of these two conditions (table 1). histologically, in ssss, the epidermis is detached from the granular layer and blisters are subcorneal in location so that the skin turns red and “slides off in sheets.” 4 this detachment occurs due to the bacteria and its exotoxin, a serine protease that destroys desmoglein 1. 5 the exfoliative toxins a and b are the specific abstract staphylococcal scalded skin syndrome (ssss) and toxic epidermal necrolysis (ten) are dermatologic conditions that have a similar clinical appearance. careful attention to clinical features, such as the coloration at the base of the blister, and histopathology are utilized to make an accurate diagnosis. while supportive therapy is required for both conditions, ssss requires appropriate antibiotics to treat the underlying staphylococcus and ten requires elimination of an offending drug (usually an antibiotic). introduction pathophysiology skin march 2018 volume 2 issue 2 copyright 2018 the national society for cutaneous medicine 136 exotoxins that cause this detachment and are only produced by approximately 5% of staphylococcal aureus bacteria. 5 these are the same toxins that produce bullous impetigo. widespread blistering only occurs in infants with immature kidneys and adults with renal failure who cannot clear the toxins rapidly. because the blistering is superficial, it does not cause scarring. the poor prognosis in adults with ssss is due to the severity of the underlying staphylococcal infection in addition to that of the significant renal impairment. it is not uncommon for adults over the age of 70 to experience chronic renal disease, and this pathological process can result in failure to excrete exotoxins produced by staphylococcal bacteria. 5 ten is a complication associated with a newly administered medication. while it is rare, it is accompanied by a mortality rate between 25% and 35% due to the extensive nature of the dermal-epidermal blistering process which is similar in its impact to a 3 rd degree burn. 2 the pathophysiological mechanism of ten is largely unknown, but current studies believe that it is due to a delayed hypersensitivity reaction along with a genetic component involving one’s abilities to destroy drug metabolites. the necrosis factor of ten is mediated by cd8 cells that induce apoptosis of keratinocytes. 6 table 1. comparison of salient features of staphylococcal scalded skin syndrome and toxic epidermal necrolysis staphylococcal scalded skin syndrome toxic epidermal necrolysis blister coloration tan or brown white mucosa involvement no yes affected skin layer subcorneal (desmoglein 1) epidermal-dermal junction (keratinocytes) mortality greater mortality in adults greater mortality in children the simplest way to distinguish ssss and ten in fitzpatrick skin types iv-vi is to examine the coloration at the base of a blister compared to normal skin. the superficial blisters of ssss show the same color at the base of the blister as adjacent skin (figure 1). the dermal-epidermal blister of ten demonstrates a white or pink base— the color of the dermis—depending upon the amount of vasculature, while surrounding skin is tan, brown, or black due to melanin pigment at and above the basal layer of the epidermis (figure 2). 7 routine histological examination is the gold standard for distinguishing ssss from ten. ssss demonstrates a subcorneal blister usually with scant inflammation (figure 3). ten shows a dermal-epidermal blister with focal dyskeratosis and areas of full thickness epidermal necrosis (figure 4). unfortunately, this approach can delay the diagnosis by 48 hours due to the processing time for standard hematoxylin and eosin sections. distinguishing features skin march 2018 volume 2 issue 2 copyright 2018 the national society for cutaneous medicine 137 frozen section histologic technology permits a faster assessment of the location of the blister, but the degree of dyskeratosis and the nature of the underlying inflammation is harder to assess when compared to permanent sections. figure 1. the base of a blister in a patient with staphylococcal scalded skin syndrome demonstrating the brown base resulting from a sub-corneal blistering process. figure 2. the base of a blister in a patient with toxic epidermal necrolysis showing the white coloration of the dermis exposed with dermal-epidermal blistering. figure 3. ssss—subcorneal splitting (granular layer) of epidermis with intracellular spongiosis. sparse interstitial lymphohistiocytic infiltrate and telangiectasias in the dermis. no epidermal necrosis is noted (h&e, 100x). provided by dr. joy king. figure 4. ten—full-thickness epidermal necrosis and underlying dermal-epidermal separation with sparse dermal inflammatory infiltrate and marked red blood cell extravasation. (h&e, 100x). provided by dr. joy king. skin march 2018 volume 2 issue 2 copyright 2018 the national society for cutaneous medicine 138 treatment for ssss generally involves supportive therapy with the addition of appropriate antibiotics to eradicate the underlying staphylococcal infection. most ssss causing strains of staphylococcal aureus are resistant to penicillin, but synthetic substitutes such as nafcillin or oxacillin are usually successful. additionally, ssss can be caused by methicillin-resistant (mrsa) bacteria, so antibiotics such as vancomycin should be utilized if mrsa is suspected. 7 infants that have a higher chance of developing a metabolic imbalance even with superficial blistering may require supportive therapy including intravenous ringer’s solution to replenish fluid loss; however, dermal substitutes such as omniderm © and suprathel © may be necessary. 8 the first step in the treatment of toxic epidermal necrolysis is to discontinue the offending medication. supportive care in a burn unit utilizing intravenous fluids is imperative to maintain metabolic equilibrium and avoid fluid-balance complications that can lead to death. topical antiseptics such as silver sulfadiazine (silvadine©) are commonly used along with non-adherent gauze to cover the blistering areas. appropriate antibiotics can be given in response to secondary infections. evolving systemic treatments for ten include short courses of glucocorticosteroids, cyclosporine, intravenous immunoglobulins, and anti-tnf biologic therapy. further studies should be conducted to delineate the position of each of these options. 9 conflict of interest disclosures: dr. brodell has participated in multi-center clinical trials for galderma laboratories, l.p., novartis, and glaxosmithkline. he serves on the editorial boards of the american medical student research journal, practice update dermatology, practical dermatology, journal of the mississippi state medical society, and skin: the journal of cutaneous medicine. funding: none. corresponding author: robert t. brodell, md department of dermatology university of mississippi medical center 2500 north state street, jackson, ms 601-815-8000 (office) 602-984-2250 (fax) rbrodell@umc.edu references: 1. lyell a. toxic epidermal necrolysis: an eruption resembling scalding of the skin. br j dermatol. 1956; 68: 355-361. 2. miliszewski ma, kirchhof mg, sikora s, et al. stevens-johnson syndrome and toxic epidermal necrolysis: an analysis of triggers and implications for improving prevention. am j med. 2016; 129: 12211225. 3. patel gk, finlay ay. staphylococcal scalded skin syndrome: diagnosis and management. am j clin dermatol. 2003; 4: 165-175. treatment skin march 2018 volume 2 issue 2 copyright 2018 the national society for cutaneous medicine 139 4. melish me, glasgow la, turner md. the staphylococcal scalded-skin syndrome: isolation and partial characterization of the exfoliative toxin. j infect dis. 1972; 125: 129-140. 5. handler mz, schwartz ra. staphylococcal scalded skin syndrome: diagnosis and management in children and adults. j eur acad dermatol venereol. 2014; 28: 1418-1423. 6. wong a, malvestiti aa, hafner mf. stevens-johnson syndrome and toxic epidermal necrolysis: a review. revista da associacao medica brasileira 1992; 62: 468-473. 7. mishra ak, yadav p, mishra a. a systemic review on staphyloccal scalded skin syndrome (ssss): a rare and critical disease of neonates. open microbiol j. 2016; 31: 150-159. 8. baartmans mg, dokter j, den hollander jc, et al. use of skin substitute dressings in the treatment of staphylococcal scalded skin syndrome in neonates and young infants. neonatology 2011; 100: 9-13. 9. paulman m, mockenhaupt m. fever in stevens-johnson syndrome and toxic epidermal necrolysis in pediatric cases: laboratory work-up and antibiotic therapy. pediatri infect dis j. 2017; 36: 513-515. fc17posterskinfixdonaldcomparison.pdf skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 491 in-depth review a systematic review of neurovascular complications in patients with pseudoxanthoma elasticum colin m. domzalski1, nancy w. wei1, mark g. lebwohl, md1 1the kimberly and eric j. waldman department of dermatology, icahn school of medicine at mount sinai hospital, new york, ny pseudoxanthoma elasticum (pxe) is a rare connective tissue disorder characterized by fragmentation and ectopic calcification of elastic fibers in the skin, ocular, and cardiovascular systems. the disease is linked to loss of function mutations in the abcc6 genes and has a prevalence of 1 in 160,000 with a 2:1 female to male ratio.1,2although there exist sporadic reports of acquired pxe, the majority of cases are inherited in an autosomal recessive fashion.3 characteristic cutaneous and ophthalmic manifestations of pxe include the presence of yellow papules in a linear or reticular pattern that often coalesce into larger plaques most commonly overlying flexural surfaces and angioid streaks in bruch’s membrane, respectively.4 additionally, gastrointestinal and retinal abstract background: pseudoxanthoma elasticum (pxe) is a rare, hereditary connective tissue disorder characterized by ectopic calcification of multiple organ systems. cardiovascular complications secondary to accelerated atherosclerosis are well-documented in published literature; however, there is a paucity of studies that reviews serious neurovascular complications including cva(cerebral vascular accident), tia(transient ischemic attack), and intracranial aneurysm in pxe patients. objective: to review current literature reporting cases of serious ischemic and hemorrhagic neurovascular complications in pxe patients as of september 2020 and reexamine current guidelines on antiplatelet therapy in pxe patients methods: a search of the pubmed database limited to english language case reports using the key words “pseudoxanthoma elasticum”, “neuro*”, “cerebr*”, “cva”, “tia”, and “aneurysm” was performed. results: a total of 67 cases of cerebral disease were reported; ranging from ages 2-71 years from 12 countries. the most common neurovascular complication seen was ischemic stroke (68.7%) followed by tia (20.8%), intracranial aneurysm (6.0%) and lastly hemorrhagic stroke (4.5%). conclusions: pxe patients have a greater incidence of ischemic strokes compared to the general population. clinicians should thus monitor this patient population for signs of neurovascular complications and carefully weigh the benefits of antiplatelet therapy in patients with known neurovascular disease against the risk of bleeding. introduction skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 492 hemorrhages are notable complications of pxe that generally result in the avoidance of long-term antiplatelet therapies in these patients.5 paradoxically, pxe patients are known to be at greater risk than the general population for coronary artery disease and peripheral artery disease, likely secondary to pxe-associated calcification and atherosclerosis.6 less commonly described in the literature are cerebrovascular complications resulting from pxe: ischemic infarction, intracranial aneurysm formation, and intracranial hemorrhage that can occur even in absence of aneurysm. although these serious neurovascular events have the potential to result in permanent disability or death, current guidelines do not recommend prophylactic antiplatelet therapy for pxe patients due to the low incidence of these acute events and aforementioned risk of hemorrhage. our systematic review of the literature aims to describe the prevalence and spectrum of neurovascular complications that may arise in pxe and use this context to re-examine current practice and guidelines regarding antiplatelet therapy in pxe patients. we performed a pubmed search using the key words “pseudoxanthoma elasticum”, “neuro*”, “cerebr*”, “cva”, “tia”, “stroke” and “aneurysm” and limited our investigation to case reports and cohort studies appearing in the english-language literature. (figure 1) articles with an irrelevant publication type such as literature reviews, conference abstracts, posters and editorials were excluded. articles wherein the full text was not available were excluded from review. we reviewed case descriptions appearing in the full text of 10 case reports and 5 cohort/cross-sectional studies in which adult and pediatric patients diagnosed with pxe presented with neurovascular complications including ischemic and hemorrhagic cva, tia and intracranial aneurysm. 10 case reports and 5 cohort studies from 12 countries were reviewed with a total of 67 cases of cerebral disease reported in pxe patients ranging from ages 2 to 71 years. publication years of the articles spanned from 1988-2020. the characteristics of pxe patients with neurovascular events from case studies vs cohort studies are listed in tables 1 and 2 respectively. overall, the most common neurovascular complications were ischemic strokes (n=46, 68.7%) followed by tias (n= 14, 20.8%). there were 4 (6.0%) reports of intracranial aneurysm formation and 3 (4.5%) cases of hemorrhagic strokes. of the 13 pxe subjects whose ischemic cvas were methods results skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 493 table 1. characteristics of pxe patients with neurovascular complications across case studies case report age male female country ischemic cva hemorrhagic cva tia aneurysm aralikatti et al12 36 1 0 united kingdom 1 0 0 0 araki et al13 63 1 0 japan 1 0 0 0 bertamino et al14 5 2 0 1 1 0 italy 2 0 0 0 bock et al15 38 1 0 switzerland 1 1 0 0 defillo et al16 nr 0 2 united states 0 0 0 2 del zotto et al17 39 0 1 italy 1 0 0 0 hirano et al18 47 54 62 1 0 0 0 1 1 japan 1 1 1 0 0 0 0 0 0 0 0 0 kumar et al19 65 1 0 india 1 0 0 1 lanfranconi et al10 62 1 0 italy 1 0 0 0 pavlovic et al20 47 49 71 0 1 0 1 0 1 serbia 1 1 1 0 1 0 table 2. characteristics of included cohort studies and cross-sectional studies study mean age (sd) male sex % country study design cerebral disease pxe patients cerebral disease n (%) kauw et al21 61 (12) 26 netherlands pfu ichemic cva, intracranial hemorrhage, intracranial aneurysm 178 31 (17%) neldner et al22 29.5 (nr) 30 usa/canada crosssectional ruptured cerebral aneurysm 100 1 (1%) omarjee et al25 nr nr france rr ischemic cva, hemorrhagic cva 151 13 (8.6%) van den berg et al23 31.4 (nr) 37 netherlands pfu ischemic cva 94 8 (8.5%) vanakker et al24 52 (nr) 40 belgium crosssectional ischemic cva 42 6 (14%) nr: not reported; pfu: prospective follow-up; rr: retrospective review skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 494 table 3. reported neurovascular complications in pxe patients ischemic cva, n (%) hemorrhagic cva, n (%) tia, n (%) intracranial aneurysm, n (%) total n neurovascular complication 46 (68.7%)* 4 (6.0%) 14 (20.8%) 3 (4.5%) 67 small artery 12 0 0 0 12 large artery 2 0 0 0 2 *percentages are calculated over total # of neurovascular complications in pxe patients (67) attributed to a specific location of infarct, 12 (92.3%) had infarctions in small arteries of the brain, whereas only 1 patient’s cva involved infarction of a large cerebral artery. (see table 3 for summary of neurovascular complications) within the individual cohort studies, van der berg et al analyzed 100 patients affected by pxe, followed-up for 17.1 years, and found 8 % incidence of stroke.23 kauw et al found a comparable 8% incidence of stroke within their 178 pxe patient cohort.21 in their smaller 42 patient cohort, vanakker et al found a 14% incidence of ischemic cvas in their smaller cohort of 42 pxe patients.24 the pathogenesis of cardiovascular disease in pxe is characterized by progressive calcification in the medial layers of medium and small sized arteries. previous studies have shown that pathogenic variants in the abcc6 gene are associated with an increased risk for ischemic stroke in humans.8 it is thus reasonable to hypothesize that pxe patients would therefore be at higher risk for ischemic and hemorrhagic neurovascular events when compared to the general population. accordingly, individual cohort studies van der berg et al and kauw et al found an 8% prevalence for ischemic cvas in pxe patients, compared to the 3% prevalence for ischemic cvas seen in the general population.9 relative risk of developing ischemic strokes is estimated to be 3.6 in pxe patients less than 65 years compared with the general population (95 % confidence interval 3.3–4.0).23,21 as demonstrated in bertamino et al and araki et al, an ischemic stroke can be a rare presenting symptom in both pediatric and adult cases of pxe.14, 13 while an increased risk for neurovascular events in the general population warrants the initiation of prophylactic antiplatelet therapy, there is no current consensus on antiplatelet in pxe patients.5 while the 100 patient cohort in van der berg et. al had 8 patients with ischemic cvas, 17 patients from the same cohort developed serious gastrointestinal bleeding, one of whom suffered a fatal hemorrhage while taking aspirin.23 liaqat et al reported a pxe patient who underwent successful coronary artery bypass surgery and was discharged on aspirin 81 mg daily and apixaban 2.5mg bid without bleeding complications.5 lanfranconi et al reported successful intravenous thrombolytic treatment of acute ischemic stroke in a 62 year old male pxe patient that resulted in resolution of neurological symptoms without bleeding complication.10 however, there were no case reports regarding use of aspirin as primary prevention for neurovascular events in pxe patients. in conclusion, pxe patients are at higher risk than the general population for discussion conclusion skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 495 developing neurovascular disease, especially ischemic stroke. clinicians should thus monitor pxe patients for neurological symptoms suggestive of neurovascular disease at visits. given that bleeding complications are more common than ischemic stroke, anti-platelet therapy as primary prevention for pxe patients without known neurovascular disease is currently not recommended. further studies must be conducted to determine the safety and efficacy of aspirin and thrombolytic therapy in the treatment and secondary prevention of neurovascular complications in pxe patients. conflict of interest disclosures: none funding: none corresponding author: nancy w wei 5 east 98th street, 5th floor new york, ny 10029 phone: 212-241-7568 fax: 212-987-1197 email: nancy.wei@mountsinai.org references: 1. bergen, arthur a. b., et al. “abcc6 and pseudoxanthoma elasticum.” pflügers archiv european journal of physiology, vol. 453, no. 5, 2006, pp. 685–691., doi:10.1007/s00424-0050039-0. 2. d'marco l, lima-martínez m, karohl c, chacín m, bermúdez v. pseudoxanthoma elasticum: an interesting model to evaluate chronic kidney disease-like vascular damage without renal disease. kidney dis (basel). 2020;6(2):92-97. doi:10.1159/000505026 3. ringpfeil f, mcguigan k, fuchsel l, et al. pseudoxanthoma elasticum is a recessive disease characterized by compound heterozygosity. j invest dermatol.2006;126(4):782-786. doi:10.1038/sj.jid.5700115 4. risseeuw s, ossewaarde-van norel j, van buchem c, spiering w, imhof sm, van leeuwen r. the extent of angioid streaks correlates with macular degeneration in pseudoxanthoma elasticum [published online ahead of print, 2020 jul 20]. am j ophthalmol. 2020;s00029394(20)30379-2. doi:10.1016/j.ajo.2020.07.022 5. liaqat m, heymann wr. anticoagulation in patients with pseudoxanthoma elasticum. skinmed. 2017;15(4):319-320. published 2017 aug 1. 6. veken, bieke van der, et al. “development of atherosclerotic plaques in a mouse model of pseudoxanthoma elasticum.” acta cardiologica, vol. 69, no. 6, 2014, pp. 687–692., doi:10.1080/ac.69.6.1000012. 7. roach, e. steve, and monica p. islam. “pseudoxanthoma elasticum.” neurocutaneous syndromes handbook of clinical neurology, 2015, pp. 215–221., doi:10.1016/b978-0-44462702-5.00015-9. 8. de vilder eyg, cardoen s, hosen mj, et al. pathogenic variants in the abcc6 gene are associated with an increased risk for ischemic stroke. brain pathol. 2018;28(6):822-831. doi:10.1111/bpa.12620 9. benjamin ej, virani ss, callaway cw, et al. heart disease and stroke statistics-2018 update: a report from the american heart association [published correction appears in circulation. 2018 mar 20;137(12):e493]. circulation. 2018;137(12):e67e492. 11 10. lanfranconi s, ghione i, valcamonica g, corti sp, bonato s, bresolin n. safety and efficacy of rt-pa treatment for acute stroke in pseudoxanthoma elasticum: the first report [published online ahead of print, 2020 may 26]. j thromb thrombolysis. 2020;10.1007/s11239020-02150-3. doi:10.1007/s11239-020-02150-3 11. li q, guo h, chou dw, et al. warfarin accelerates ectopic mineralization in abcc6(-/-) mice: clinical relevance to pseudoxanthoma elasticum. am j pathol. 2013;182(4):1139-1150. doi:10.1016/j.ajpath.2012.12.037 12. aralikatti ak, lee mw, lipton me, kamath gg. visual loss due to cerebral infarcts in pseudoxanthoma elasticum. eye (lond). 2002;16(6):785-786. doi:10.1038/sj.eye.6700173 13. araki y, yokoyama t, sagawa n, et al. pseudoxanthoma elasticum diagnosed 25 years after the onset of cardiovascular disease. intern med. 2001;40(11):1117-1120. doi:10.2169/internalmedicine.40.1117 14. bertamino m, severino m, grossi a, et al. abcc6 mutations and early onset stroke: two cases of a typical pseudoxanthoma elasticum. eur j paediatr neurol. 2018;22(4):725-728. doi:10.1016/j.ejpn.2018.04.002 skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 496 15. bock, andreas, and guido schwegler. "intracerebral haemorrhage as first manifestation of pseudoxanthoma elasticum." clinical neurology and neurosurgery 110.3 (2008): 262264. 16. defillo a, nussbaum es. intracranial aneurysm formation in siblings with pseudoxanthoma elasticum: case report. j neurosurg sci. 2010;54(3):105-107. 17. del zotto e, ritelli m, pezzini a, et al. clinical, neuroradiological and molecular features of a patient affected by pseudoxhantoma elasticum associated to carotid rete mirabile: case report. clin neurol neurosurg. 2012;114(6):758761. doi:10.1016/j.clineuro.2011.12.031 18. hirano t, hashimoto y, kimura k, uchino m. rinsho shinkeigaku. 1996;36(5):633-639. 19. kumar gn, ragi kv, nair ps. pseudoxanthoma elasticum with cerebrovascular accident. indian j dermatol venereol leprol. 2007;73(3):191-193. doi:10.4103/0378-6323.32746 20. pavlovic am, zidverc-trajkovic j, milovic mm, et al. cerebral small vessel disease in pseudoxanthoma elasticum: three cases. can j neurol sci. 2005;32(1):115-118. doi:10.1017/s0317167100016991 21. kauw f, kranenburg g, kappelle lj, et al. cerebral disease in a nationwide dutch pseudoxanthoma elasticum cohort with a systematic review of the literature. j neurol sci. 2017;373:167-172. doi:10.1016/j.jns.2016.12.053 22. k.h. neldner, pseudoxanthoma elasticum, clin. dermatol. 6 (1) (1988) 1–159. 23. van den berg js, hennekam rc, cruysberg jr, et al. prevalence of symptomatic intracranial aneurysm and ischaemic stroke in pseudoxanthoma elasticum. cerebrovasc dis. 2000;10(4):315-319. doi:10.1159/000016076 24. vanakker, olivier m., et al. “novel clinico‐ molecular insights in pseudoxanthoma elasticum provide an efficient molecular screening method and a comprehensive diagnostic flowchart.” wiley online library, john wiley & sons, ltd, 21 dec. 2007, onlinelibrary.wiley.com/doi/10.1002/humu.9514/a bstract. 25. omarjee l, fortrat jo, larralde a, et al. internal carotid artery hypoplasia: a new clinical feature in pseudoxanthoma elasticum. j stroke. 2019;21(1):108-111. doi:10.5853/jos.2018.02705 skin july 2018 volume 2 issue 4 copyright 2018 the national society for cutaneous medicine 252 brief article nail biopsy in the diagnosis of systemic amyloidosis cc briscoe md a , zp nahmias md b , ha jones md b , is rosman md b,c , mj anadkat md b a washington university school of medicine b division of dermatology, washington university school of medicine c department of pathology and immunology, washington university school of medicine amyloidosis is characterized by the extracellular deposition of insoluble fibrillary proteins. al amyloidosis (or primary amyloidosis) involves the deposition of amyloid light-chain due to an underlying plasma cell dyscrasia, while aa amyloidosis (or secondary amyloidosis) involves the deposition of serum amyloid a, most often due to a chronic inflammatory condition. cutaneous manifestations of amyloidosis, seen in almost half of patients, classically include purpura, ecchymoses, petechiae, and waxy papules and nodules. 1 we present a case in which dystrophic nail changes were the sole presenting sign of al amyloidosis. a 60-year-old woman with common variable immunodeficiency and a 13-year history of igg monoclonal gammopathy of undetermined significance (mgus) was seen in clinic due to nail changes of six months’ duration. examination of the fingernails demonstrated distal nicking and onychomadesis, as well as onychorrhexis and slight swelling of the proximal nail folds (figure 1). the toenails showed signs of fungal infection but no other changes, and her dermatologic exam was otherwise unremarkable. on follow up four months later, the patient described increased tenderness of her fingernails while doing housework. examination showed worsening of her nail abstract a 60-year-old woman with a 13-year history of monoclonal gammopathy of unknown significance (mgus) presented with worsening nail dystrophy. prior workup for systemic amyloidosis had been unrevealing, and no other signs of cutaneous disease were present. nail biopsy was consistent with amyloid deposition, and the patient subsequently underwent autologous hematopoietic stem cell transplantation for al amyloidosis. in light of the growing literature regarding nail changes as a presenting sign of systemic amyloidosis and the promising utility of nail biopsy, we suggest a low threshold for biopsy in appropriate patients when nail changes characteristic of amyloidosis are refractory to conventional treatment. introduction case report skin july 2018 volume 2 issue 4 copyright 2018 the national society for cutaneous medicine 253 changes, and a 4 mm punch biopsy of the left thumb nail matrix was performed. on h&e, the biopsy showed dull pink globules filling widened papillae within the nail matrix. staining with crystal violet and pas (figure 2) were consistent with amyloid deposition. at the time of initial presentation to our clinic, the patient was asymptomatic and abdominal fat pad biopsy, skeletal surveys, and cardiac magnetic resonance imaging had been unremarkable. she was being observed without therapy by her oncologist. following the nail biopsy, repeat abdominal fat pad biopsy was positive for amyloid deposition, though the skeletal survey and cardiac workup remained unremarkable. bone biopsy showed 5 percent monoclonal plasma cells and no amyloid. the patient was diagnosed with al amyloidosis and underwent autologous hematopoietic stem cell transplantation within three months of her nail biopsy. figure 1. nail dystrophy consistent with amyloidosis. distal nicking, onychorrhexis, and slight swelling of the proximal nail folds are seen. figure 2. pas stain of the nail matrix. positive pas staining is consistent with amyloid deposition. diagnosis of systemic amyloidosis remains challenging because its presentation depends on the organ system(s) affected and is often nonspecific. moreover, confirmation of amyloid on tissue biopsy is required. in cases of suspected amyloidosis with known organ impairment, the first diagnostic step is generally biopsy of the affected organ. in cases with no specific organ involvement, the first step is often a screening biopsy of the abdominal fat pad, rectal mucosa, or minor salivary glands. abdominal fat pad biopsy, the preferred site, has a reported sensitivity of anywhere from 14 to over 90 percent, though this yield decreases substantially in patients with lower total body amyloid burdens. 2 once diagnosed, the prognosis of al amyloidosis is highly variable depending on the organ systems affected. historically the prognosis has been dismal, but recent advances in treatment and earlier detection discussion skin july 2018 volume 2 issue 4 copyright 2018 the national society for cutaneous medicine 254 rates have resulted in improved survival. early detection therefore plays a critical role in maximizing outcomes. while nail changes are a relatively rare finding of systemic amyloidosis, they have been noted in at least 32 cases to date (table 1). 1, 3-12 the nail changes most often described include increased brittleness, longitudinal ridging, and onycholysis, though chronic paronychia and verrucous subungual plaques have also been observed. 1, 10-11 easy bruising, purpura, ecchymoses, and/or petechiae represent the most common cutaneous findings overall, present in 44 percent of the cases. alopecia and macroglossia were the next most common mucocutaneous findings, seen in 39 percent and 23 percent of cases, respectively. of note, 19 percent of the patients had a history of carpal tunnel syndrome, higher than its estimated prevalence in the general population. nail changes were the sole presenting sign of amyloidosis in almost 20 percent of the cases, highlighting its potential role in early detection. moreover, in the 23 cases with a clear timeline, dystrophic nail changes began on average more than two and a half years prior to systemic presentation. in all cases where nail biopsy was undertaken, amyloid deposition was confirmed, indicating its promising diagnostic utility. interestingly, one case even describes resolution of the nail dystrophy one year after autologous stem cell transplant, suggesting the possibility of reversibility with treatment. 6 in conclusion, we suggest a low threshold for consideration of nail bed biopsy in patients with trachyonychia, onychorrhexis, and onycholysis refractory to conventional treatment. this is particularly appropriate if other signs of systemic amyloidosis are present, for example macroglossia, alopecia, carpal tunnel syndrome, or known mgus. used in this manner, nail matrix biopsy may provide a reliable method for the early diagnosis of systemic amyloidosis, analogous to the current first-line diagnostic step of biopsy of an affected organ. conflict of interest disclosures: none funding: none corresponding author: cristopher c. briscoe, md 4901 forest park avenue, suite 502 st. louis, mo 63110 (314) 362-9859 (office) briscoec@go.wustl.edu references: 1. renker t, haneke e, röcken c, borradori l. systemic light-chain amyloidosis revealed by progressive nail involvement, diffuse alopecia and sicca syndrome: report of an unusual case with a review of the literature. dermatology. 2014; 228: 97-102. 2. quarta cc, gonzalez-lopez e, gilbertson ja, et al. diagnostic sensitivity of abdominal fat aspiration in cardiac amyloidosis. eur heart j. 2017; ehx047. 3. rao rr, yong wc, wasko mc. systemic light chain amyloidosis mimicking rheumatic disorders. case rep med. 2016; 2016: 7649510. 4. que skt, sloan b, dadras ss. trachyonychia, cutis laxa, and easy bruising of the skin. jama dermatol. 2014; 150: 1357-1358. skin july 2018 volume 2 issue 4 copyright 2018 the national society for cutaneous medicine 255 5. fernandez-flores a, castañóngonzález ja, guerrero-ramos b, et al. systemic amyloidosis presenting with glans penis involvement. j cutan pathol. 2014; 41: 791-796. 6. oberlin ke, wei ex, cho-vega jh, tosti a. nail changes of systemic amyloidosis after bone-marrow transplantation in a patient with multiple myeloma. jama dermatol. 2016; 152: 1395-1396. 7. shim jh, oh sh, jun jy, et al. trachyonychia as the presenting sign of myeloma-associated amyloidosis. int j dermatol. 2016; 55: e410-e412. 8. barja j, piñeyro f, almagro m, et al. systemic amyloidosis with an exceptional cutaneous presentation. dermatol. online j. 2013; 19(1). 9. xu j, tahan s, jan f, et al. nail dystrophy as the initial sign of multiple myeloma-associated systemic amyloidosis. j cutan pathol. 2016; 43: 543-545. 10. ahmed i, cronk js, crutchfield ce, dahl mv. myeloma-associated systemic amyloidosis presenting as chronic paronychia and palmodigital erythematous swelling and induration of the hands. j am acad dermatol. 2000; 42: 339-342. 11. tausend w, neill m, kelly b. primary amyloidosis-induced nail dystrophy. dermatol. online j. 2014; 20(1). 12. etienne m, denizon n, maillard h. anomalies unguéales révélant une amylose systémique al. rev med interne. 2015; 36: 356-358. skin november 2017 volume 1 issue 3 copyright 2017 the national society for cutaneous medicine 161 brief articles minocycline-induced agranulocytosis presenting as ecthyma gangrenosum katherine nolan mda, reema ishteiwy phda, john alexis mbchbb,c, martin n. zaiac mdd,e, anna j. nichols md phda a department of dermatology and cutaneous surgery, university of miami miller school of medicine, miami, fl, usa b department of pathology, mount sinai medical center, miami beach, fl, usa c department of pathology, herbert wertheim college of medicine at florida international university, miami, fl, usa d department of dermatology, herbert wertheim college of medicine at florida international university, miami, fl, usa e greater miami skin and laser center, miami beach, fl, usa a 51-year-old woman with a history of rheumatoid factor negative rheumatoid arthritis was admitted for tender abscesses, intermittent spiking fevers, chills, night sweats, malaise, shortness of breath and non-productive cough. she was diagnosed with rheumatoid arthritis 16 years prior to abstract a 51-year-old female with a history of rheumatoid arthritis was admitted for progressive fevers, chills and malaise. five weeks prior, she started minocycline for an ra exacerbation. two weeks after starting minocycline she developed an abscess on her right ankle that was treated at an urgent care facility with ceftriaxone and trimethoprim-sulfamethoxazole. she had minimal improvement so was switched to clindamycin. she developed additional abscesses on her right ankle and right axilla and spiking fevers so she was treated with incision and drainage under general anesthesia. routine blood work obtained prior to surgery revealed severe neutropenia (0.74 103/ul) and the patient was urgently referred to the emergency department. skin biopsy was obtained on admission and revealed ulceration, necrosis, acute and chronic inflammation, vasculitis with vascular thrombosis and rod-shaped bacteria in blood vessel walls and lumina consistent with ecthyma gangrenosum. the following day tissue and blood cultures confirmed the growth of pseudomonas aureginosa. bone-marrow biopsy showed decreased granulopoiesis and hematopoiesis, and a diagnosis of minocycline-induced agranulocytosis presenting as ecthyma gangrenosum was made. the patient had dramatic improvement with appropriate antibiotic therapy, discontinuation of minocycline and initiation of filgrastrim. she has remained healthy without recurrence for 17 months. case report skin november 2017 volume 1 issue 3 copyright 2017 the national society for cutaneous medicine 162 presentation. her rheumatoid arthritis was successfully treated with minocycline 100 mg daily for 6 months and subsequently her disease went into remission. five weeks prior to admission she developed worsening joint pain and swelling. given her prior treatment success with minocycline, her rheumatologist prescribed minocycline 100 mg daily. three weeks prior to admission she developed a tender violaceous papule with surrounding erythema on the right lateral leg. over the following 3 weeks the patient was treated at an urgent care center four times. she was diagnosed with an abscess and treated with intramuscular ceftriaxone, trimethoprimsulfamethoxazole ds twice a day, clindamycin 300 mg three times a day. she developed additional abscesses at distant sites and ultimately was treated with incision and drainage of the abscesses under general anesthesia because of the progression of symptoms despite oral antibiotics. the following day, the patient was notified that blood work drawn prior to surgery revealed an abnormally low white blood cell count. she was referred to the emergency department for further evaluation and admission for intravenous antibiotics. at the time of admission, review of systems was positive for intermittent spiking fevers, chills, night sweats, malaise, shortness of breath and non-productive cough. she denied unintentional weight loss. the patient had a complete blood count 3 months prior, which was normal. on admission the patient had temperature of 98.2f, heart rate 77, respiratory rate 20, blood pressure 113/77. she was initially treated with vancomycin but continued to develop intermittent episodes of fever (tmax 103.2f) a blood pressure of 79/50 so meropenem was added. pertinent laboratory analyses included decreased white blood cell count of 0.74 10 3 /ul, hemoglobin 11.2 g/dl, hematocrit 33.5% (mean cell volume 87.5 fl) and absolute neutrophil count of 0.16 10 3 /ul but increased platelet count 514 10 3 /ul, esr 72 mm/hr, crp 153 mg/l and lactic acid 3 mmol/l. chest x-ray showed peripheral prominent patchy airspace opacities more confluent in the bilateral upper lung fields and bilateral lower lung fields, blunting of the costophrenic angles consistent with multifocal pneumonia and small bilateral pleural effusions. dermatology was consulted and a skin biopsy was obtained for tissue culture and histology. histopathologic analysis of the edge of the right lateral leg ulcer showed ulceration, necrosis, acute and chronic inflammation, vasculitis with vascular thrombosis, and rod-shaped bacteria in blood vessel walls, lumina and the dermis. with this result, vancomycin and meropenem were discontinued, piperacillintazobactam, ciprofloxacin and filgrastrim were initiated. the following day, tissue culture and blood cultures grew pseudomonas aureginosa. peripheral blood flow cytometry failed to reveal a monoclonal b-cell proliferation or an aberrant t-cell immunophenotype and there was no evidence of a discrete blast population. bone marrow biopsy showed decreased granulopoiesis and hematopoiesis with adequate iron stores and without evidence of fibrosis, necrosis, granulomatous inflammation, lymphoma, leukemia, or cells extrinsic to the marrow. based on these findings, a diagnosis of minocycline-induced agranulocytosis presenting as ecthyma gangrenosum was made. skin november 2017 volume 1 issue 3 copyright 2017 the national society for cutaneous medicine 163 minocycline had been discontinued upon admission to the hospital. the patient had a dramatic improvement after piperacillintazobactam, ciprofloxacin and filgrastrim were initiated; vital signs and white blood cell count normalized and repeat blood cultures were negative for growth of p. aeruginosa. figure 1. clinical and histopathological images of ecthyma gangrenosum that developed in a patient treated with minocycline for rheumatoid arthritis. clinical progression of the initial lesion on the right ankle from a dusky, violaceous and tender papule to a necrotic ulcer in the weeks prior to hospitalization, images were taken by the patient (a-c). appearance of the lesions on the day of presentation to the hospital (d-e). histopathology revealed ulceration, necrosis and mixed acute and chronic inflammation (f-g) and vessels with vasculitis and rod shaped bacteria within the lumen and wall (h). minocycline is a semisynthetic tetracycline derivative antibiotic commonly used for the treatment of aerobic and anerobic gram positive and negative bacterial as well as fungal infections. interestingly, minocyline is involved with a wide variety of biological actions other than anti-microbial activity. for example, this drug decreases the production of substances causing inflammation, such as prostaglandins, metalloproteinases and leukotrienes and therefore is used to treat the inflammation associated with acne vulgaris as well as that inherent to autoimmune diseases such as rheumatoid arthritis. although minocycline has been used as a successful treatment for many diseases, serious but rare adverse events such as neutropenia associated autoimmune hepatitis and minocycline-induced lupus with neutropenia have been reported. 1-2 druginduced agranulocytosis occurs with a discussion skin november 2017 volume 1 issue 3 copyright 2017 the national society for cutaneous medicine 164 variety of classes of medications including dipyrone, diclofenac, ticlopidine, antithyroid drugs such as methimazole, carbamazepine, clozapine, and trimethoprim-sulfamethoxazole. a rapid decrease in agranulocytes often occurs within hours 1 to 2 days after administration of the drug. the recovery of the neutrophil count can take an average of 9 days to return to within normal limits (range: 9-24 days). 3 treatment of neutropenia usually consists of supportive care, including broadspectrum antibiotics for febrile patients. 4 delivery of granulocyte colony stimulating factors such as g-csf and gm-csf, has been shown to contribute to rapid healing by partial recovery of neutrophil production and function. 4 the neutropenia caused by minocycline therapy is thought to be immunologic in origin. although the mechanism(s) are unclear, it is thought that the unique metabolism of minocycline may be responsible for the increase in serious adverse events compared to other tetracycline antibiotics. minocycline reactive metabolites may bind tissue macromolecules causing direct cell damage or these metabolites may act as haptens and elicit immune responses in a secondary manner. 5 in conclusion, we present a rare case of minocycline-induced agranulocytosis presenting as ecthyma grangrenosum in a previously healthy patient with rapid resolution upon immediate discontinuation of minocycline and subsequent treatment with piperacillin-tazobactam, ciprofloxacin and filgrastrin. seventeen months after this illness, she remains in excellent health without any recurrences. although neutropenia due to minocycline appears to be a rare adverse event, it is important to draw attention to these known severe sequelae given the frequently with which minocycline is used. immediate discontinuation of the offending medication, initiation of broad-spectrum antibiotics and consideration of the use of granulocyte colony-stimulating factors may help improve outcomes in similar cases. conflict of interest disclosures: none. funding: none. corresponding author: katherine nolan, m.d. university of miami miller school of medicine 1600 nw 10th ave, rosensteil science medical building, room 2023a miami, florida 33136 305-243-4472 (office) 305-243-6191 (fax) katherine.nolan@jhsmiami.org references: 1. garrido-mesa n, zarzuelo a, gálvez j. review. minocycline: far beyond an antibiotic. br j pharmacol. 2013;169(2):337-52. 2. ahmed f, kelsey pr, shariff n. lupus syndrome with neutropenia following minocycline therapy a case report. int j lab hematol. 2008;30(6):543-5. 3. pick, a., nystrom k. nonchemotherapy druginduced neutropenia and agranulocytosis: could medication be the culprit? j pharm pract 2014;27(5):447-452. 4. gregorini m, castello m, rampino t, bosio f, bedino g, esposito p, borroni g., dal canton a. gmcsf contributes to prompt healing of ecthyma gangrenosum lesions in kidney transplant recipient. j nephrol. 2012;25(1):137-9. 5. ishikawa t, sakurai y, tanaka m, daikoku n, ishihara t, nakajima m, miyagawa s, yoshioka a. ecthyma gangrenosum-like lesions in a healthy child after infection treated with antibiotics. pediatr dermatol. 2005;22(5):453-6. http://www.ncbi.nlm.nih.gov/pubmed/23441623 http://www.ncbi.nlm.nih.gov/pubmed/18983308 http://www.ncbi.nlm.nih.gov/pubmed/18983308 http://www.ncbi.nlm.nih.gov/pubmed/18983308 http://www.ncbi.nlm.nih.gov/pubmed/16191001 http://www.ncbi.nlm.nih.gov/pubmed/16191001 powerpoint presentation andrew blauvelt1, steven kempers2, seth forman3, edward lain4, suzanne bruce5, glynis ablon6, abel jarell7, michael bukhalo8, robert lieberman9, jane fang10, tirbanibulin phase iii study group 1oregon medical research center, portland, or, usa; 2associated skin care specialists, fridley, mn, usa; 3forward clinical trials, tampa, fl, usa; 4austin institute for clinical research, pflugerville, tx, usa; 5the center for skin research, houston, tx, usa; 6the ablon skin institute research center, manhattan beach, ca, usa; 7activmed practices & research, portsmouth, nh, usa; 8arlington dermatology, arlington heights, il, usa; 9henderson dermatology research, henderson, nv, usa; 10athenex, inc., buffalo, ny, usa tirbanibulin ointment 1%, a novel inhibitor of tubulin polymerization and src kinase signaling, for the treatment of actinic keratosis (ak): results from two pivotal phase iii studies table 3. maximal post-baseline severe (grade 3) lsrs (safety population) • actinic keratosis (ak) are precancerous lesions that if left untreated may lead to invasive squamous cell carcinoma1 • tirbanibulin (kx2-391, kx01) is a synthetic, highly selective, novel inhibitor of tubulin polymerization and src kinase signaling developed as a first-in-class topical formulation for the treatment for ak2 • previous phase i and ii studies demonstrated that tirbanibulin ointment 1% was active against ak lesions on the forearm and face or scalp, respectively. local skin reactions (lsrs) were mostly transient and mildto-moderate in severity, and tirbanibulin was well tolerated3,4 • this poster presents results from two phase iii, double-blinded, vehiclecontrolled, randomized, parallel-group, multicenter studies (kx01-ak003 [nct03285477]; kx01-ak-004 [nct03285490]) that evaluated the efficacy and safety of tirbanibulin versus vehicle in adults with ak lesions on the face or scalp synopsis tirbanibulin phase iii study group: of kx01-ak-003 (nct03285477) and kx01-ak-004 (nct03285490): jerry bagel, joshua berlin, norman bystol, anne chapas, joel cohen, j clay davis, jess demaria, sunil dhawan, janet dubois, robert fixler, joseph fowler jr, scott fretzin, david greenstein, scott guenthner, fashat hamzavi, george han, c william henke iii, catherine hren, john humeniuk, stephen huang, sarah jackson, sasha jazayeri, peter jenkin, timothy jochen, terry jones, debra liu, keith loven, kappa meadows, adnan nasir, terri nutt, maureen olivier, james pehoushek, catherine pointon, edward primka, marta rendon, jeffrey rosen, todd schlesinger, joel schlessinger, james solomon, kenneth stein, melody stone, dow stough, leonard swinyer, jens thiele, douglas thomas, aldo trovato, anne truitt, eduardo tschen, john tu, stephen tyring, darryl wong, martin zaiac, matthew zook. editorial support, under the direction of the authors, was provided by gemma mcgregor, phd, of cmc affinity, a division of mccann health medical communications ltd, glasgow, uk, in accordance with good publication practice (gpp3) guidelines and was funded by almirall sa. acknowledgments ‒ kx01-ak-003: 44% vs 5% (complete clearance); 68% vs 16% (partial clearance), respectively ‒ kx01-ak-004: 54% vs 13% (complete clearance); 76% vs 20% (partial clearance), respectively • significantly higher complete and partial clearance rates for tirbanibulin compared with vehicle were also demonstrated in subgroup analyses for age, baseline ak lesion count, gender, skin type, and treatment location (face or scalp) in both studies (p<0.001) • to assess the efficacy and safety of tirbanibulin compared with vehicle in participants with ak lesions on the face or scalp objective • adult participants with 4–8 typical, visible ak lesions in a 25 cm2 treatment area on the face or scalp were enrolled (2:1) in the study • participants were randomized to receive either tirbanibulin ointment 1% or vehicle (1:1); treatment was self-applied once-daily for 5 consecutive days and left in place for ~12 hours • the primary efficacy endpoint was complete (100%) clearance of ak lesions at day 57 • partial (≥75% reduction of ak lesions) clearance was a secondary efficacy endpoint • safety assessments included adverse events (aes) and monitoring of lsrs including erythema, flaking/scaling, crusting, swelling, vesicles/pustules, and erosions/ulcers as graded on a 4-point scale (0 [absent] to 3 [severe]); composite lsr score was the sum of all six lsr grades (possible range: 0–18) methods this study was sponsored by athenex, inc. authors are either investigators (ab, sk, sf, el, sb, ga, aj, mb, rl) or consultants (sk, sf, jf) of athenex, inc. disclosures 1. fernandez figueras mt. j eur acad dermatol venereol. 2017;31 suppl 2:5-7 2. smolinksi, mp, et al. j med chem. 2018;61:4707-4719 3. dubois j, et al. phase i study of tirbanibulin ointment 1%, a novel src phosphorylation and tubulin polymerization inhibitor, in subjects with actinic keratosis. poster presented at the 6th annual practical symposium, beaver creek, co, usa, august 8–11, 2019 4. dubois j, et al. phase ii study of tirbanibulin ointment 1%, a novel src phosphorylation and tubulin polymerization inhibitor, for actinic keratosis. poster presented at the 6th annual practical symposium, beaver creek, co, usa, august 8–11, 2019 references conclusions • tirbanibulin ointment 1% once-daily for 5 days resulted in higher overall complete ak clearance rates at day 57 than vehicle in two phase iii studies (kx01-ak-003: 44% vs 5%; kx01-ak-04: 54% vs 13%, respectively; p<0.0001) • statistically significant differences were demonstrated in all subgroups analyzed for the face and scalp • most treatment-related teaes were mild-to-moderate, transient application site pruritus, or pain that did not require treatment • mean composite lsr scores were low and peaked at day 8 before resolving by day 29 • over 99% of participants completed the full 5-day self-application of tirbanibulin study participants • overall 702 participants were enrolled from 62 study sites in the us (n=351 from 31 sites per study where each site participated in only one study); over 99% of participants were treatment compliant • demographics and baseline characteristics were similar between treatment groups; most participants were white males (mean age, 70 years) and had a fitzpatrick skin type of i–ii (table 1) • the intent-to-treat and safety population were the same for both studies and included all randomized participants who were dosed. participants who discontinued early were considered non-responders results table 1. demographics and baseline characteristics (itt population) kx01-ak-003 (n=351) kx01-ak-004 (n=351) tirbanibulin (n=175) vehicle (n=176) tirbanibulin (n=178) vehicle (n=173) mean age, years 69.5 70.2 69.1 70.2 male, n (%) 147 (84) 154 (88) 158 (89) 150 (87) white, n (%) 175 (100) 175 (99) 177 (99) 173 (100) fitzpatrick skin type i-ii, n (%) 123 (70) 142 (81) 126 (71) 120 (69) median baseline ak lesion count 6 6 6 6 treatment area face:scalp ratio 119:56 121:55 119:59 118:55 safety • treatment-related treatment-emergent aes (teaes) were reported in 56 participants receiving tirbanibulin (kx01-ak-003, n=20 [11%]; kx02-ak004, n=36 [20%]) and 35 participants treated with vehicle (kx01-ak-003, n=16 [9%]; kx02-ak-004, n=19 [11%]) ‒ most treatment-related teaes were mild-to-moderate, transient application site pruritus or pain that did not require treatment • two tirbanibulin-treated participants did not complete treatment for reasons unrelated to study drug but remained in the study • in the vehicle-treated group, two participants discontinued early from the study for reasons unrelated to treatment • no discontinuations or serious aes related to tirbanibulin were reported • no ocular exposure led to ocular aes, and there were no clinically significant abnormal electrocardiograms, laboratory findings, physical examinations, or vital signs local skin reaction assessments • lsrs were mostly mild-to-moderate erythema and flaking/scaling • mean composite lsr scores were low for tirbanibulin, peaked on day 8 and were resolved by day 29 (figure 1) • the most common maximal post-baseline severe (grade 3) lsrs were erythema and flaking/scaling (table 3) table 2. complete (100%) and partial (≥75%) clearance rates of ak lesions (itt population) kx01-ak-003 (n=351) kx01-ak-004 (n=351) tirbanibulin (n=175) vehicle (n=176) p-value tirbanibulin (n=178) vehicle (n=173) p-value 100% clearance, n (%) 77 (44%) 8 (5%) <0.0001 97 (54%) 22 (13%) <0.0001 face 50% 6% <0.0001 61% 14% <0.0001 scalp 30% 2% <0.0001 41% 11% 0.0003 ≥75% clearance, n (%) 119 (68%) 29 (16%) <0.0001 136 (76%) 34 (20%) <0.0001 subgroup analysis age <65 years old 45% 2% <0.0001 63% 10% <0.0001 ≥65 years old 44% 5% <0.0001 51% 13% <0.0001 gender female 61% 14% 0.0007 85% 13% <0.0001 male 41% 3% <0.0001 51% 13% <0.0001 baseline ak lesion count 4–6 ak lesions 49% 6% <0.0001 61% 13% <0.0001 7–8 ak lesions 31% 2% <0.0001 42% 11% 0.0002 fitzpatrick skin type i or ii 45% 5% <0.0001 54% 13% <0.0001 iii, iv, v, or vi 42% 3% <0.0001 56% 13% <0.0001 ak actinic keratosis; itt, intent-to-treat ak actinic keratosis; itt, intent-to-treat kx01-ak-003 (n=351) kx01-ak-004 (n=351) n (%) tirbanibulin (n=175) vehicle (n=176) tirbanibulin (n=178) vehicle (n=173) erythema 5 (3) 0 17 (10) 0 flaking/scaling 11 (6) 0 20 (11) 1 (<1) crusting 2 (1) 0 5 (3) 0 swelling 1 (<1) 0 1 (<1) 0 vesicles/pustules 1 (<1) 0 1 (<1) 0 erosions/ulcers 0 0 0 0 lsrs, local skin reactions 0 2 4 6 8 10 12 14 16 18 1 5 8 15 29 57 m e a n c o m p o s it e l s r study day 0 2 4 6 8 10 12 14 16 18 1 5 8 15 29 57 m e a n c o m p o s it e l s r study day tirbanibulin vehicle kx01-ak-003 (n=351) kx01-ak-004 (n=351) lsrs were graded on a 4-point scale (0=absent; 1=mild [slightly or barely perceptible]; 2=moderate [distinct presence]; 3=severe [marked/intense]). composite lsr score is the sum of all six lsr (erythema, flaking/scaling, crusting, swelling, vesicles/pustules, erosions/ulcers) grades with a possible range of 0–18 lsr, local skin reaction figure 1. mean composite lsr scores (safety population) presented at the fall clinical dermatology conference®, october 17–20, 2019, wynn hotel, las vegas, nv, usa efficacy • complete (100%) and partial (≥75%) clearance rates were significantly higher in participants administered tirbanibulin compared with vehicle in both studies (p<0.0001) (table 2) acknowledgements: medical writing support was provided by prescott medical communications group (chicago, il) with financial support from ortho dermatologics; ortho dermatologics is a division of bausch health us, llc • presented at winter clinical dermatology conference 2023 • january 13-18, 2023 • waimea, hi synopsis � topical retinoids are a mainstay in the treatment of acne, but cutaneous irritation may limit their use and patient adherence � tolerability of topical retinoids can be impacted by the retinoid itself, the concentration used, and the vehicle used for its delivery,1 as well as skin hydration � newer, thirdand fourth-generation topical retinoid formulations have been developed using lower concentrations, enhanced vehicles, and/or novel retinoids to be efficacious while providing a more patient-friendly tolerability profile2 � low-dose tazarotene 0.045% lotion was developed using polymeric emulsion technology to provide uniform and rapid distribution of tazarotene and hydrating ingredients on the skin in a highly spreadable formulation3 objectives � to compare the tolerability of tazarotene 0.045% lotion with adapalene 0.3% gel and trifarotene 0.005% cream methods � healthy adults (≥18 years) with fitzpatrick skin types i–ii and normal upper back skin were enrolled in two identical 12-day modified cumulative irritation patch studies � in each study, two patches loaded with active ingredients and one control patch (no study product) were placed on participants’ upper back in a randomized, double-blind fashion � in study 1, active patches were loaded with 0.1 cc of adapalene 0.3% gel or tazarotene 0.045% lotion; in study 2, active patches were loaded with 0.1 cc of trifarotene 0.005% cream or tazarotene 0.045% lotion (figure 1) • patches were replaced every 2–3 days, for a total of 5 applications � at each patch removal, dermal effects were assessed using an 8-point scale (0=no evidence of irritation; 7=strong reaction spreading beyond application site) and other effects were assessed using a 7-point scale (0=no other effects; 6=small petechial erosions and/or scabs) • assessments were analyzed using a wilcoxon signed-rank test; group differences were considered significant at a p-value of ≤0.05 comparison of cutaneous irritation with repeated application of tazarotene 0.045% lotion, adapalene 0.3% gel, and trifarotene 0.005% cream zoe d draelos, md1; patricia farris, md2; hilary baldwin, md3,4; emil a tanghetti, md5 1dermatology consulting services, high point, nc; 2 tulane university school of medicine department of dermatology, new orleans, la; 3 the acne treatment and research center, brooklyn, ny; 4robert wood johnson university hospital, new brunswick, nj; 5 center for dermatology and laser surgery, sacramento, ca results study 1: adapalene 0.3% gel vs tazarotene 0.045% lotion � 20 white adults (22–69 years; 95% female) were enrolled and completed this study � tazarotene 0.045% lotion and adapalene 0.3% gel were both assessed as mildly irritating, with dermal effects mean scores <1 (figure 2) • differences in dermal effects mean scores between drugs were not statistically significant at any assessment, though there was slightly less irritation overall with tazarotene lotion than adapalene gel (highest mean scores: 0.50 and 0.80, respectively) � other effects mean scores were negligible (≤0.05) with both drugs � no irritation was observed at the control patch site at any study visit figure 2. study 1: irritation potential of adapalene 0.3% gel vs tazarotene 0.045% lotion tazarotene 0.045% lotion adapalene 0.3% gel control tazarotene 0.045% lotion adapalene 0.3% gel control 0.0 0.5 1.0 1.5 2.0 2.5 3.0 1 2 3 4 5 6 m e a n s co re , d e rm a l e ff e ct s a. dermal effects b. other effects m e a n s co re , o th e r e ff e ct s 0.0 0.5 1.0 1.5 2.0 2.5 3.0 1 2 3 4 5 6 visit visit 1=minimal erythema; barely perceptible 2=definite erythema, readily visible; minimal edema/ papular response 3=erythema and papules 3=glazing with peeling and cracking 2=marked glazing 1=slight glazed appearance *p<0.05; **p<0.01; ***p<0.001 vs control. patches were applied at visits 1–5 after any skin assessments were made. visits 1–6 correspond to study days 1, 3, 5, 8, 10, and 12, respectively. figure 3. study 2: irritation potential of trifarotene 0.005% cream vs tazarotene 0.045% lotion tazarotene 0.045% lotion trifarotene 0.005% cream control tazarotene 0.045% lotion trifarotene 0.005% cream control 0.0 0.5 1.0 1.5 2.0 2.5 3.0 1 2 3 4 5 6 m e a n s co re , d e rm a l e ff e ct s a. dermal effects b. other effects m e a n s co re , o th e r e ff e ct s 0.0 visit visit 0.5 1.0 1.5 2.0 2.5 3.0 1 2 3 4 5 6 1=slight glazed appearance 2=marked glazing 3=glazing with peeling and cracking 1=minimal erythema; barely perceptible 2=definite erythema, readily visible; minimal edema/ papular response 3=erythema and papules *p<0.05; **p<0.01; ***p≤0.001 vs control. #p<0.05; ##p<0.01; ###p≤0.001 trifarotene 0.005% cream vs tazarotene 0.045% lotion. patches were applied at visits 1–5 after any skin assessments were made. visits 1–6 correspond to study days 1, 3, 5, 8, 10, and 12, respectively. study 2: trifarotene 0.005% cream vs tazarotene 0.045% lotion � 20 adults (22–74 years; 90% female; 90% white, 10% african american) were enrolled and completed this study � dermal effects mean scores with trifarotene cream were significantly greater than with tazarotene lotion at the first assessment (2 days after first patch application; p<0.05) and increased over the remaining visits (highest mean scores: 2.20 vs 0.70, respectively; p<0.001, all; figure 3) � other effects mean scores were significantly greater with trifarotene cream than with tazarotene lotion, beginning at the second assessment (4 days after first patch application) and continuing through remaining visits (highest mean scores: 0.70 vs 0.20, respectively; p<0.01, all) � no irritation was observed at the control patch site at any study visit � images of representative participants are shown in figure 4 figure 4. study 2: participant photographs at visit 6 (day 12; final assessment) control tazarotenetrifarotene controltazarotene trifarotene 42-year-old male effects score trifarotene tazarotene control dermal 3 0 0 other 1 0 0 30-year-old female effects score trifarotene tazarotene control dermal other 2 1 0 1 0 0 individual results may vary. references 1. leyden j, et al. j drugs dermatol. 2004;3(6):341–651. 2. baldwin h, et al. am j clin dermatol. 2021;22:315–327. 3. tanghetti ea, et al. j dermatolog treat. 2019;1–8. 4. culp l, et al. j cutan med surg. 2015;19(6):530–538. author disclosures zoe draelos received funding from ortho dermatologics to conduct the research presented in this poster. patricia farris serves as an advisor, speaker or consultant to beauty, la roche posay, neostrata, neutrogena, nutraceutical wellness, and usk. hilary baldwin has served as advisor, investigator, and on speakers’ bureaus for almirall, cassiopea, foamix, galderma, ortho dermatologics, sol gel, and sun pharma. emil tanghetti has served as speaker for novartis, ortho dermatologics, sun pharma, lilly, galderma, abbvie, and dermira; served as a consultant/clinical studies for hologic, ortho dermatologics, and galderma; and is a stockholder for accure. conclusions � in a modified cumulative irritation study, tazarotene 0.045% lotion was significantly less irritating than trifarotene 0.005% cream � tazarotene 0.045% lotion was numerically less irritating than adapalene 0.3% gel, one of the best-tolerated topical retinoids2,4 � tazarotene 0.045% lotion allows for simultaneous, uniform, and rapid delivery of hydrating ingredients along with less than half the concentration of tazarotene versus other commercially available 0.1% formulations3 • the lower retinoid concentration combined with moisturizing/ hydrating ingredients (sorbitol, light mineral oil, diethyl sebacate, water3) in a proprietary polymeric mesh vehicle may help minimize instances of retinoid-induced irritationfigure 1. study design visit 1 (day 1) visit 2 (day 3) visit 3 (day 5) visit 4 (day 8) visit 5 (day 10) visit 6 (day 12) patches placed: irritation assessed: tazarotene 0.045% lotion adapalene 0.3% gel control (no drug) study 1: tazarotene 0.045% lotion study 2: trifarotene 0.005% cream control (no drug) the order of patches on participants’ backs was randomized. figure 2. obs clinical grading improvements in ashen appearance and dry skin parameters figure 3. obs improved ashen appearance, dryness, flaking, tactile roughness and radiance after 2 weeks of daily use figure 4. obs and aho significantly improved dryness, scaling, cracking, and roughness figure 5. comparison of daily obs and aho for treatment of dry heel skin demonstrated comparable efficacy introduction results results conclusions conclusions methods methods objective objective (obs) on large areas of dry, ashen skin of women with darker skin complexions skin on heels compared to aquaphor healing ointment (aho) at week 1 (p<0.05) and week 2 (p<0.001) compared with baseline and compared with untreated legs (p<0.05) (figure 1) parameters for both obs and aho at days 5, 10, and 15 compared to baseline (p<0.001) (figure 4) (figure 5) such as the lower legs skin on the heels, and were not statistically different subjects study design assignment) for 2 weeks assessments subjects study design the other once daily for 15 days assessments tm weber,1 ce arrowitz,1 li jiang,2 k qian,2 a filbry3 1beiersdorf inc., wilton, ct, usa; 2thomas j. stephens & associates, richardson, tx, usa; 3beiersdorf ag, hamburg, germany efficacy of an ointment body spray to improve the appearance of dry, ashy skin and alleviate moderate to severe dryness on the heel figure 1. obs significantly improved skin hydration of dry skin compared with baseline and untreated skin 19.6 23.5 24.9 20.4 20.1 21.1 10 12 14 16 18 20 22 24 26 28 30 baseline wk 1 wk 2 treated untreated n=31 c o rn eo m et er u n it s skin hydration a,c b,c obs=ointment body spray ap<0.05 vs baseline bp<0.001 vs baseline cp<0.05 vs control 5.7 4.3 3.4 5.8 5.8 5.8 0.0 1.0 2.0 3.0 4.0 5.0 6.0 7.0 baseline week 1 week 2 0.0 1.0 2.0 3.0 4.0 5.0 6.0 7.0 baseline week 1 week 2 0.0 1.0 2.0 3.0 4.0 5.0 6.0 7.0 baseline week 1 week 2 ashen appearance m ea n c lin ic al g ra d in g s co re s a,b a,b a,b a,b 5.7 4.8 4.1 5.7 5.9 5.9 a,b a,b dryness 5.5 4.1 3.1 5.5 5.6 5.6 flaking n=31 ap<0.001 vs baseline bp<0.001 vs control treated untreated 0 1 2 3 4 5 6 7 baseline day 5 day 10 day 15 baseline day 5 day 10 day 15 baseline day 5 day 10 day 15 baseline day 5 day 10 day 15 m ea n c lin ic al g ra d in g s co re 0 1 2 3 4 5 6 7 scaling dryness cracking 0 1 2 3 4 5 6 7 0 1 2 3 4 5 6 7 obs aho a a a a a a a a a a a a a a a a a a a a a a a a roughness n=18ap=0.001 vs baseline aquaphor healing ointment’s (aho) efficacy in reducing moderately to severely dry skin is well established. however, application of ointments on large areas can be messy and challenging. ointment body spray (obs) was developed to enable the delivery two clinical studies were conducted to evaluate the efficacy of obs. study a study b untreated: baseline untreated: baseline treated: baseline treated: baseline untreated: week 2 – no change untreated: week 2 – no change treated: week 2 – clinical improvement treated: week 2 – clinical improvement baseline day 15 obs obsaho aho all parameters compared with baseline and untreated legs at week 1 and week 2 (p<0.001) (figure 2, tactile roughness and radiance data not shown) fc17posterbeiersdorfweberefficacyointmentheel.pdf skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 160 brief article clinical and histological spectrum of primary cutaneous b-cell lymphoma in an ethnically-diverse group of patients: a case series sahira farooq, bs1,, madeline frizzell, bs, ms2, emily limmer3, ritu swali, md4, stephen tyring, md, phd, mba4,5 1mcgovern medical school, houston, tx 2 texas a&m university college of medicine, houston, tx 3university of texas southwestern medical school, dallas, tx 4department of dermatology, university of nebraska medical center, omaha, ne 5department of dermatology, mcgovern medical school at ut houston health science center, houston, tx while dermatologic findings may not be what initially come to mind when identifying lymphomas, these neoplasms can and do present cutaneously. primary cutaneous lymphomas, which are diagnosed with only skin involvement, can be of b or t cell origin, with b cells making up merely 2530% of cases. they commonly present with nodules or with plaques or papules.1 previously lymphomas were classified as simply hodgkin or non-hodgkin.2 however, due to their varied origin as well as their diverse presentations, these groups have been divided further into more descriptive and representative groups. broadly, nonhodgkin lymphoma derived from b cells include diffuse large b cell lymphoma (dlbcl), burkitt lymphoma, follicular lymphoma, and marginal zone lymphoma, among others.3 here, we present the cases of three ethnically diverse patients with distinct clinical and histological forms of cutaneous b cell lymphoma. patient a a 67-year-old hispanic male, with a past medical history of coronary artery disease, hypertension, hyperlipidemia, and type 2 diabetes, presented to the dermatology clinic with a two-month history of a red nodule on his left ear. he denied pain, pruritus, and/or bleeding. he had been using triamcinolone 1% ointment on the lesion with minor improvement. on clinical examination, abstract primary cutaneous lymphomas, which are diagnosed with only skin involvement, can be of b or t cell origin. due to their varied origin as well as their diverse presentations, these groups have been divided further into more descriptive and representative groups. the subtypes are primary cutaneous marginal zone lymphoma (pcmzl), primary cutaneous follicle center lymphoma (pcfcl), primary cutaneous diffuse large b cell lymphoma, leg type (pcdlbcl-lt) and intravascular large b-cell lymphoma. here, we present the cases of three ethnically diverse patients with distinct clinical and histological forms of cutaneous b cell lymphoma. introduction case presentation skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 161 there was a pearly nodule on the left antitragus (figure 1). a shave biopsy was performed to rule out basal cell carcinoma. histopathological examination revealed an atypical dense infiltrate of lymphocytes with a grenz zone. immunohistochemistry demonstrated cd20+, cd3+, bcl-2+, cd10+, bcl-6+, and ki67+, while mum1-, cd30-, and cd21-. results were consistent with germinal center type diffuse large b-cell lymphoma. patient b a 79-year-old african american male, with a history of diabetes and hypertension, presented to the dermatology clinic with a scalp lesion present for the past two years. he noted that the lesion stung upon manipulation. no treatment had been pursued up to this point. on physical exam, there was a notable skin-colored nodule (33mm x 22mm) on the left crown of the scalp (figure 2). a punch biopsy was performed. histopathology revealed sheets of markedly atypical lymphoid cells. immunohistochemical stains were cd20+, ki-67+, cd3+, cd4+, cd8+, cd30+, cd10-, cd23-, s100-, ae1/3-. lesional cells were mum+, consistent with diffuse large b-cell lymphoma, leg type. patient c a 73-year-old caucasian male with a past medical history of hypertension, diabetes, and anemia, presented to the dermatology clinic with a bleeding growth on his right upper extremity for the past month. clinical examination revealed a cluster of 2-4mm pink-red papules and vesicles on his right wrist (figure 3). a shave biopsy was performed. immunohistochemistry demonstrated cd20+, cd3+, cd4+, cd5+, cd8+, bcl-2+, cd10-, cd30-, s100-, cd21-, eber-. the lambda/kappa ratio was elevated by in-situ hybridization. the diagnosis of marginal zone b-cell lymphoma was favored. the patients were referred to oncology for further work up and therapy. figure 1. patient a. a pearly nodule, reminiscent of basal cell carcinoma, representing germinal center type diffuse large b-cell lymphoma on the ear of a 67year-old hispanic male. figure 2: patient b. symptomatic, skin-colored lesion representing diffuse large b-cell lymphoma, leg type, on the scalp of a 79-year-old african american male. skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 162 figure 3: patient c. bleeding, erythematous papules and vesicles representing marginal zone b-cell lymphoma on the wrist of a 73-year-old caucasian male. primary cutaneous lymphomas, which are skin-limited lymphoproliferative neoplasms or b or t cell origin, are uncommon, occurring with an estimated incidence of 0.5 to 1 case per 100,000 people annually.4 primary cutaneous b-cell lymphomas (pcbcls) make up around one-quarter of the cutaneous lymphomas.4 according to the world health organization european organization for research and treatment of cancer (who-eortc) 2018 classifications for pcl, there are 4 subtypes of pcbcls with one provisional subtype being ebv mucocutaneous ulcer. the subtypes are primary cutaneous marginal zone lymphoma (pcmzl), primary cutaneous follicle center lymphoma (pcfcl), primary cutaneous diffuse large b cell lymphoma, leg type (pcdlbcl-lt) and intravascular large b-cell lymphoma.5 primary cutaneous lymphomas (pcls) are, by definition, a cutaneous manifestation that is not secondary to extracutaneous spread, so their diagnosis requires a thorough workup to exclude systemic disease. a biopsy is necessary to analyze morphology, immunohistochemistry (ihc), and staging to exclude systemic disease.6 immunophenotype workup is also necessary to differentiate between types of cutaneous lymphomas. presence of the cd20 marker differentiates b-cell lymphomas from t-cell lymphomas.9 additional markers are tested to determine the pattern and location of infiltrate to distinguish between the types of cutaneous b-cell lymphomas.9 panel recommendations include cd3, cd5, cd10, bcl2, bcl6, and mum1. additional testing can include cd21, cd23, cd43, cyclin d1, ki-67, immunoglobulins igm and igd, as well as kappa/lambda light chain analysis.4 who’s current classification system of pcbcls considers primary cutaneous diffuse large b-cell lymphoma-leg type (pcdlbcl-lt) to be the only primary cutaneous diffuse large b-cell lymphoma. while patients a and b were both diagnosed with pcdlbcls because there have been multiple reports of pcdlbcl that do not fit into the leg-type description, there is still debate as to whether they represent an atypical variant of the leg type or a separate entity.10 pcdlbcl-lt commonly presents in elderly females with rapidly progressive tumors on the legs. however, 15-20% of the lesions present at locations outside the legs, such as our patient b.5,6 on the other hand, pcdlbcl presents more commonly on the trunk of elderly men with frequent involvement of the limbs, head and neck regions.10 histologically, the leg type is characterized by diffuse large cells infiltrating to subcutaneous tissue with rare intermingled reactive t lymphocytes; pcdlbcl has a histologic pattern that discussion skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 163 figure 4: primary cutaneous lymphoma: stratification and demographic data. stratification of primary cutaneous b-cell lymphoma into its subgroups is shown in the blue boxes. demographic data overall and with respect to specific groups is detailed in the gray boxes. includes large centroblastic or immunoblastic cells. based on expression of bcl-6, cd10, and mum-1, diffuse large b-cell lymphomas can be further divided into germinal center (gc) and non-germinal center subtypes.11 given that bcl-6 and cd10 are markers for germinal center b-cells, patient a’s ihc results were consistent with a diagnosis of pcdlbcl, gc subtype.11 patient’s b’s ihc results were consistent with a diagnosis of pcdlbcl-lt, as leg type is usually positive for bcl2, mum1 and bcl6, but negative for cd10.4 primary cutaneous marginal zone lymphomas (pcmzl) is an indolent lymphoma, classically presenting as solitary or multifocal erythematous to brown-colored plaques, papules, or nodules. they typically appear in young adults distributed on the skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 164 trunk or upper extremities.4,5 pruritus is commonly associated with pcmzl, but pain, night sweats, fever and weight loss are not expected.5 on histopathology, pcmzl reveals a nodular or diffuse mixed infiltrate of small, marginal zone b-cells, lymphoplasmacytic cells, plasma cells, and reactive t cells. these findings typically spare the epidermis and superficial papillary dermis. marginal zone b cells are characteristically bcl‐2 and mum-1 positive, but lack bcl‐6 or cd10 expression.4,6 the immunohistochemistry features of patient c’s biopsy and the characteristics of the tumor on histopathology favored a diagnosis of pcmzl. another pcbcl worth mentioning, although not found in our three patients, is primary cutaneous follicle center b cell (pcfcl). the median age of presentation is 60 and typically presents with localized skin lesions on the head, neck and trunk.4 pcfcl is characterized by a predominance of large centrocytes and centroblasts that stain positive for cd20, bcl-6, cd10 and negative for bcl-2 and mum-1. this lymphoma has an excellent prognosis and can be easily managed with local radiotherapy.5 there are limited trials and data regarding treatment for pcbcls, and therapy is primarily guided by whether the nature of the lymphoma is indolent or aggressive.4 no standard of treatment exists for the indolent lymphomas, such as pcmzl and pcfcl, however, treatment options include local radiotherapy, excision, and intralesional steroids.4,7 prognosis is excellent with 5year survival of > 95%.4,7 in contrast, pcdlbcl is aggressive in nature, and first line treatment is intravenous rituximab with a combination of chemotherapy agents.4,7 prognosis is poorer with 5-year survival of 50-70%.4,7 relapses and systemic spread are common for pcdlbcl despite therapy.7 overall, though pcbcls are uncommon, it is important for clinicians to be aware of the diverse clinical and histological presentations of these indolent lymphomas, because they have a relatively good prognosis with appropriate therapy. the more aggressive, leg type lymphoma must be closely managed given its poorer prognosis. optimal care of pcbcls may involve a multidisciplinary approach, consisting of dermatology, medical oncology, and radiation oncology.6 conflict of interest disclosures: none funding: none corresponding author: ritu swali, md 985645 nebraska medical center omaha, ne, 68198 phone: 402-552-5525 email: rituswali@gmail.com references: 1. kempf w, kazakov dw, mitteldorf c. cutaneous lymphomas: an update. part 2: b-cell lymphomas and related conditions. am j dermatopathol, 2014. 36(3): p. 197-208; quiz 209-10. 2. alizadeh aa, et al. distinct types of diffuse large b-cell lymphoma identified by gene expression profiling. nature. 2000. 403(6769): p. 503-11. 3. teras, lr, et al., 2016 us lymphoid malignancy statistics by world health organization subtypes. ca cancer j clin. 2016. 66(6): p. 443-459. 4. malachowski sj, sun j, chen p-l, seminariovidal l. diagnosis and management of cutaneous b-cell lymphomas. dermatologic clinics. 2019;37(4):443-454. 5. willemze r, cerroni l, kempf w, berti e, facchetti f, steven h. swerdlow, elaine s. jaffe; the 2018 update of the who-eortc classification for primary cutaneous lymphomas. blood. 2019; 133 (16): 1703–1714. conclusion skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 165 6. campbell sm, peters sb, zirwas mj, wong hk, campbell sm. immunophenotypic diagnosis of primary cutaneous lymphomas: a review for the practicing dermatologist. j clin aesthet dermatol. 2010;3(10):21-25. 7. sica a, vitiello p, caccavale s, et al. primary cutaneous dlbcl non-gcb type: challenges of a rare case. open med (wars). 2020;15:119– 125. published 2020 mar 19. 8. bradford pt, devesa ss, anderson wf, toro jr. cutaneous lymphoma incidence patterns in the united states: a population-based study of 3884 cases. blood. 2009;113(21):5064-5073. 9. wilcox ra (2013), cutaneous b‐cell lymphomas: 2013 update on diagnosis, risk‐stratification, and management. am. j. hematol., 88: 73-76. 10. hans cp, weisenburger dd, greiner tc, et al. confirmation of the molecular classification of diffuse large b-cell lymphoma by immunohistochemistry using a tissue microarray. blood. 2004;103(1):275-282. 11. goyal a, leblanc re, carter jb. cutaneous bcell lymphoma. hematol oncol clin north am. 2019;33(1):149-161. skin january 2018 volume 2 issue 1 copyright 2018 the national society for cutaneous medicine 2 original research risk factors for the development of acute radiation dermatitis in breast cancer patients jennifer j. parker, md phd a , alfred rademaker phd b , eric d. donnelly md a , jennifer n. choi, md c northwestern university feinberg school of medicine, chicago, il a department of radiation oncology, robert h. lurie comprehensive cancer center b department of preventative medicine, division of biostatistics c department of dermatology, division of oncodermatology, robert h. lurie comprehensive cancer center abstract objective: adjuvant breast radiation increases the risk of acute dermatitis. we aimed to identify patient and treatment characteristics that may increase this risk to help individualize the prevention and management of radiation-induced skin toxicities. methods/materials: we analyzed 320 women with breast cancer who received adjuvant radiation for increased risk of acute dermatitis based upon age, bmi, histology, stage, chemotherapy, radiation fractionation, whole breast dose, tumor bed boost dose, total dose, diuretics use, smoking, diabetes, autoimmune disease, and chronic immunosuppression. univariate logistic regression was used to compare each factor across the dermatitis groups. significant factors were analyzed in a multivariate analysis. results: on univariate analysis, grade 3 dermatitis was more likely with a 1 unit bmi increase (or 1.084, p=0.005). grade 2 dermatitis risk increased with each 100 cgy increase in breast dose (or 1.14, p=<0.001). every 100 cgy total dose increase resulted in higher grade 2 and 3 dermatitis risks (or 1.13 and 1.45, p=<0.001). there was decreased risk of grade 2 and 3 dermatitis with hypofractionated radiation (grade 2: or 0.16, p=<0.0001; grade 3: or 0.08, p=0.017). on multivariate analysis, higher risk of grade 2 (or 1.06, p=0.014) and 3 dermatitis (or 1.12, p=<0.001) remained with increasing bmi. higher total dose increased grade 3 dermatitis (or 1.35, p=0.019). hypofractionated radiation continued to decrease the risk of grade 2 dermatitis (or 0.08, p=<0.001). conclusion: lower bmi, lower total dose, and hypofractionated radiation were beneficial to decrease dermatitis risk. the other risk factors were not significant within our patient population. skin january 2018 volume 2 issue 1 copyright 2018 the national society for cutaneous medicine 3 adjuvant radiation therapy following breastconserving surgery for invasive breast cancer is widely utilized. after long-term follow-up in large randomized trials, this approach showed equal efficacy to mastectomy without significant differences in survival. 1-3 a meta-analysis by the early breast cancer trialists’ collaborative group analyzed data from multiple randomized trials that showed decreased 10-year recurrence and 15-year breast cancer death with radiation therapy after breastconserving surgery. 4 in addition, adjuvant radiation therapy has been studied extensively in noninvasive breast cancer and has been shown to have a local control benefit after breast-conserving surgery as well. 5-6 as a result, many patients undergo radiation therapy for their noninvasive and invasive breast cancer. one of the most common side effects is the development of acute skin toxicities. up to 90% of patients develop dose-dependent skin reaction within the treated area that may include mild erythema, dry desquamation, moist desquamation, and, rarely, ulceration. 7 studies have shown acute skin reactions are associated with the development of late skin toxicities that lead to poor cosmetic outcomes and decreased quality of life, including pain, impaired body image, and impaired functioning. 8 one prospective study showed that in long-term follow-up, patients who developed acute skin toxicities were at a higher risk of telangiectasias and fibrosis. 9 this study seeks to better determine which patient and/or treatment factors are detrimental or protective against developing acute dermatitis in breast cancer patients. understanding these factors could help individualize the prevention and management of radiation-induced skin toxicities in patients undergoing breast cancer treatment. the medical records of 320 breast cancer patients treated between 2011 and 2014 with histologically confirmed ductal carcinoma in situ, invasive ductal carcinoma, or invasive lobular carcinoma were obtained. patients who were american joint committee on cancer (ajcc) stage 0 to 3 were included. those with metastatic disease were excluded. patients may or may not have received chemotherapy. the patients received radiation therapy treatment in the northwestern memorial hospital department of radiation oncology after breast-conserving surgery. the patients were either treated in the supine or prone position with three-dimensional conformal radiotherapy (3d-crt) administered daily, monday through friday, as whole breast photon radiotherapy using standard or hypofractionation. patients may or may not have received a tumor bed boost using photon or electron radiotherapy. patients who received nodal radiotherapy were excluded. acute skin toxicity was measured using the national cancer institute−issued common terminology criteria for adverse events (ctcae) version 4.0. dermatitis from radiation was categorized from grades 1 to 5. faint erythema or dry desquamation were classified as grade 1. moderate to brisk erythema; patchy, moist desquamation mostly confined to skin folds and creases; and moderate edema were recorded as grade 2. moist desquamation in areas other than skin folds and creases and bleeding induced by minor trauma or abrasion were classified as grade 3. life-threatening introduction methods skin january 2018 volume 2 issue 1 copyright 2018 the national society for cutaneous medicine 4 consequences, skin necrosis or ulceration of full thickness dermis, spontaneous bleeding from involved site, and skin graft indicated were recorded as grade 4; death was recorded as grade 5. this information was retrospectively evaluated in mosaiq (radiation oncology care management software). epic, the electronic medical record, was used to obtain the patient’s cancer and noncancer clinical history, including patient-specific parameters (age, body mass index [bmi], medications, smoking status, comorbidities), tumorspecific parameters (tumor histology and stage), and treatment-specific parameters (whole breast fractionation schedule and dose, tumor bed boost dose). descriptive data were summarized using means and standard deviations for continuous data and percentages for categorical data. for both univariate and multivariate analysis of correlates of dermatitis, logistic regression with a generalized logit related the 3-category measure of dermatitis to either categorical or continuous correlates. odds ratios for the relationship between dermatitis grades 2 and 3 relative to the reference category grade 1 were calculated from the regression model. both a global p-value for the 3 category dermatitis variable and individual pvalues for each of grades 2 and 3 were calculated. p-value <0.05 was deemed significant. patient, tumor, and treatment characteristics the average age was 56.4 years and average bmi was 28.4. most patients did not have a history of diuretic use, type 2 diabetes mellitus, autoimmune disease, or chronic immunosuppression. in addition, the majority of patients were nonsmokers. these patients most often had noninvasive or early-stage breast cancer and did not receive chemotherapy. furthermore, the majority of patients were treated with standard whole breast radiation therapy (wbrt) fractionation (table 1). univariate analysis of dermatitis risk factors univariate analysis was performed to determine if age, weight, height, bmi, wbrt dose, tumor bed boost dose, total breast dose, wbrt dose fractionation, chemotherapy use, smoking status, years smoked, diuretic use, history of type 2 diabetes mellitus, history of autoimmune disease, and chronic immunosuppression were risk factors (table 2). weight was found to be a risk factor for the development of grade 3 dermatitis as compared to grade 1 dermatitis. weight was related to grade 3 dermatitis, with odds ratios being the foldincrease in odds for every 10-pound increase in weight (or 1.114, 95% ci 1.002-1.020, p=0.017). results skin january 2018 volume 2 issue 1 copyright 2018 the national society for cutaneous medicine 5 in addition, for a 1-unit increase in bmi, grade 3 dermatitis was more likely (grade 3: or 1.084, 95% ci 1.025-1.146, p=0.005). for every 100-cgy increase in whole breast dose, grade 2 dermatitis was more likely (or 1.14, 95% ci 1.06-1.23, p=<0.001). a similar phenomenon was seen with a 100cgy increase in tumor bed boost dose. a 100-cgy increase in total dose (wbrt and tumor bed boost dose) resulted in a higher risk of grade 2 and grade 3 dermatitis (grade 2: or 1.13, 95% ci 1.06-1.22, p=<0.001 and grade 3: or 1.45, 95% ci 1.17-1.80, p=<0.001). when patients received hypofractionated rt, they were less likely to have grade 2 or grade 3 dermatitis (or grade 2: or 0.16, 95% ci 0.08-0.32, p=<0.0001 and grade 3: or 0.08, 95% ci 0.01-0.42, p=0.017). autoimmune disease increased the risk of grade 3 dermatitis as compared to grade 1 (or 4.89, 95% ci 1.92-2.33, p=0.05). age, height, smoking status, years smoked, diuretic use, chemotherapy, diabetes, and chronic immunosuppression did not affect risk for development of dermatitis. skin january 2018 volume 2 issue 1 copyright 2018 the national society for cutaneous medicine 6 table 1. patient, tumor, and treatment characteristics all patients dermatitis=1 dermatitis=2 dermatitis=3 n mean (sem) n mean(sem) n mean(sem) n mean(sem) age 320 56.4 (0.6) 91 56.7 (1.1) 200 56.4 (0.7) 28 56.5 (2.1) weight (lb) 319 165.7 (2.5) 91 159.4 (4.2) 200 166.3 (3.2) 28 182.4 (7.9) height (in) 316 64.0 (0.2) 90 64.4 (0.3) 198 63.8 (0.2) 28 63.8 (0.4) bmi 316 28.4 (0.4) 90 27.0 (0.7) 198 28.6 (0.5) 28 31.4 (1.2) wbrt dose 320 4732 (19) 91 4627 (41) 201 4775 (21) 28 4768 (53) tumor bed boost dose 311 1224 (17) 86 1193 (31) 197 1219 (22) 28 1357 (50) total dose 311 5963 (19) 86 5841 (44) 197 5993 (21) 28 6125 (43) years smoking 91 18.6 (1.3) 23 21.1 (2.6) 62 18.0 (1.7) 6 15.3 (3.6) n % n % n % n % tnm stage 0 111 34.6 29 31.9 75 37.3 6 21.4 1 135 42.1 42 46.2 80 39.8 13 46.4 2 72 22.4 20 22.0 43 21.4 9 32.1 3 3 0.9 0 0 3 1.5 0 0 histology idc 196 61.1 57 62.6 120 59.7 19 67.9 dcis 111 34.6 29 31.9 75 37.3 6 21.4 ilc 8 2.5 3 3.3 4 2.0 1 3.6 mixed 5 1.6 2 2.2 2 1.0 1 3.6 other 1 0.3 0 0 0 0 1 3.6 chemotherapy given 1 yes 65 21.0 15 17.2 41 21.1 9 32.1 2 no 244 78.0 72 82.8 153 78.9 19 67.9 missing 12 diuretics 1 yes 44 13.8 12 13.2 29 14.4 3 11.1 2 no 275 86.2 79 86.8 172 85.6 24 88.9 missing 2 current smoker 1 yes 9 2.8 1 1.1 7 3.5 1 3.6 2 no 311 97.2 90 98.9 194 96.5 27 96.4 former smoker 1 yes 97 30.9 27 30.0 64 32.5 6 22.2 2 no 217 69.1 63 70.0 133 67.5 21 77.8 missing 7 diabetes mellitus 1 yes 22 6.9 5 5.5 16 8.0 1 3.6 2 no 298 93.1 86 94.5 185 92.0 27 96.4 missing 1 autoimmune disease 1 yes 10 3.1 3 3.3 3 1.5 4 14.3 2 no 309 96.9 88 96.7 197 98.5 24 85.7 missing 2 chronic immunosuppresion 1 yes 6 1.9 2 2.2 3 1.5 1 3.6 2 no 313 98.1 89 97.8 197 98.5 27 96.4 missing 2 wbrt dose fractionation hypofractionated 42 13.1 28 30.8 13 6.5 1 3.6 standard 278 86.9 63 69.2 188 93.5 27 96.4 missing 1 skin january 2018 volume 2 issue 1 copyright 2018 the national society for cutaneous medicine 7 table 2. univariate analysis of dermatitis risk factors univariate generalized logistic regression odds ratio (or) definition or 95% ci p-value* age 0.97 grade 2 vs grade 1, odds ratio of grade 2 for a 5 year increase in age 0.997 0.973 1.021 0.80 grade 3 vs grade 1, odds ratio of grade 3 for a 5 year increase in age 0.998 0.958 1.040 0.92 weight (lb) 0.058 grade 2 vs grade 1, odds ratio of grade 2 for a 10 pound increase in weight 1.042 0.979 1.010 0.20 grade 3 vs grade 1, odds ratio of grade 3 for a 10 pound increase in weight 1.114 1.002 1.020 0.017 height (in) 0.28 grade 2 vs grade 1, odds ratio of grade 2 for a 3 inch increase in height 0.82 0.63 1.06 0.12 grade 3 vs grade 1, odds ratio of grade 3 for a 3 inch increase in height 0.80 0.53 1.21 0.29 bmi 0.018 grade 2 vs grade 1, odds ratio of grade 2 for a 1 unit increase in bmi 1.037 0.997 1.079 0.07 grade 3 vs grade 1, odds ratio of grade 3 for a 1 unit increase in bmi 1.084 1.025 1.146 0.005 wbrt dose 0.002 grade 2 vs grade 1, odds ratio of grade 2 for a 100 cgy increase in wbrtdose 1.14 1.06 1.23 <0.001 grade 3 vs grade 1, odds ratio of grade 3 for a 100 cgy increase in wbrtdose 1.13 0.99 1.29 0.06 tumor bed boost dose 0.044 grade 2 vs grade 1, odds ratio of grade 2 for a 100 cgy increase in boost 1.03 0.95 1.13 0.49 grade 3 vs grade 1, odds ratio of grade 3 for a 100 cgy increase in boost 1.19 1.04 1.37 0.014 wbrt + boost <0.001 grade 2 vs grade 1, odds ratio of grade 2 for a 100 cgy increase in total dose 1.13 1.06 1.22 <0.001 grade 3 vs grade 1, odds ratio of grade 3 for a 100 cgy increase in total dose 1.45 1.17 1.80 <0.001 years smoking 0.49 grade 2 vs grade 1, odds ratio of grade 2 for a 1 year increase in years smoked 0.98 0.95 1.02 0.34 grade 3 vs grade 1, odds ratio of grade 3 for a 1 year increase in years smoked 0.96 0.89 1.04 0.32 tnm stage no odds ratios calculated due to small sample sizes in the multiple subcategories 0.69 histology no odds ratios calculated due to small sample sizes in the multiple subcategories 0.85 chemotherapy given 0.25 grade 2 vs grade 1, odds ratio of grade 2 for chemo vs no chemo 1.29 0.67 2.48 0.45 grade 3 vs grade 1, odds ratio of grade 3 for chemo vs no chemo 2.27 0.86 5.99 0.10 diuretics use 0.88 grade 2 vs grade 1, odds ratio of grade 2 for diuretic use vs no diuretic use 1.11 0.54 2.29 0.78 grade 3 vs grade 1, odds ratio of grade 3 for diuretic use vs no diuretic use 0.82 0.21 3.16 0.78 current smoker 0.54 grade 2 vs grade 1, odds ratio of grade 2 for current smoker vs not current smoker 3.25 0.39 16.8 0.27 grade 3 vs grade 1, odds ratio of grade 3 for current smoker vs not current smoker 3.33 0.20 55.1 0.40 former smoker 0.55 grade 2 vs grade 1, odds ratio of grade 2 for former smoker vs not former smoker 1.12 0.65 1.93 0.67 grade 3 vs grade 1, odds ratio of grade 3 for former smoker vs not former smoker 0.67 0.24 1.84 0.43 diabetes mellitus (dm) 0.58 grade 2 vs grade 1, odds ratio of grade 2 for dm vs no dm 1.49 0.53 4.19 0.45 grade 3 vs grade 1, odds ratio of grade 3 for dm vs no dm 0.64 0.07 5.69 0.69 autoimmune disease (aid) 0.01 grade 2 vs grade 1, odds ratio of grade 2 for aid vs no aid 0.45 0.09 2.26 0.33 grade 3 vs grade 1, odds ratio of grade 3 for aid vs no aid 4.89 1.02 23.3 0.05 chronic immunosuppresion (ci) 0.74 grade 2 vs grade 1, odds ratio of grade 2 for ci vs no ci 0.68 0.11 4.13 0.67 grade 3 vs grade 1, odds ratio of grade 3 for ci vs no ci 1.65 0.14 18.9 0.69 wbrt dose fractionation <0.0001 grade 2 vs grade 1, odds ratio of grade 2 for hypofractionation vs standard 0.16 0.08 0.32 <0.0001 grade 3 vs grade 1, odds ratio of grade 3 for hypofractionation vs standard 0.08 0.01 0.42 0.017 *p≤0.05 significance level skin january 2018 volume 2 issue 1 copyright 2018 the national society for cutaneous medicine 8 table 3. multivariate analysis of dermatologic risk factors multivariate generalized logistic regression odds ratio (or) definition or 95% ci p-value* bmi 0.002 grade 2 vs grade 1, odds ratio of grade 2 for a 1 unit increase in bmi 1.06 1.01 1.11 0.014 grade 3 vs grade 1, odds ratio of grade 3 for a 1 unit increase in bmi 1.12 1.05 1.19 <0.001 total dose 0.006 grade 2 vs grade 1, odds ratio of grade 2 for a 100 cgy increase in total dose 0.92 0.80 1.07 0.29 grade 3 vs grade 1, odds ratio of grade 3 for a 100 cgy increase in total dose 1.35 1.05 1.74 0.019 fractionation 0.002 grade 2 vs grade 1, odds ratio of grade 2 for hypofractionation vs standard 0.08 0.02 0.31 <0.001 grade 3 vs grade 1, odds ratio of grade 3 for hypofractionation vs standard 0.53 0.02 6.16 0.64 *p≤0.05 significance level multivariate analysis of dermatologic risk factors multivariate analysis assessed variables significant in the univariate analysis including bmi, total dose, and fractionation schedule. the variables selected did not include those from univariate analysis that were related to another variable and did not pass the p-value test for multivariate analysis. thus, weight, wbrt dose, and tumor bed boost dose were not included in the analysis. autoimmune disease was not examined due to the small number of patients. the higher risk of grade 2 (or 1.06, 95% ci 1.01-1.11, p=0.014) and grade 3 dermatitis (or 1.12, 95% ci 1.05-1.19, p=<0.001) persisted with increasing bmi. total breast dose still increased the risk of grade 3 dermatitis (or 1.35, 95% ci 1.051.74, p=0.019). hypofractionated rt still decreased the risk of grade 2 dermatitis. however, decreased risk of grade 3 dermatitis as compared to standard fractionated rt was no longer statistically significant (table 3). significant progress has been made over the years to reduce potential toxicities of external beam radiation therapy after breastconserving surgery. there are now improved radiation techniques including 3dcrt and intensity-modulated radiation therapy, which allow for better dose homogeneity. 10-12 hypofractionated courses of radiation therapy to the breast have been found to have better long-term cosmetic outcomes in randomized control trials. 13 discussion skin january 2018 volume 2 issue 1 copyright 2018 the national society for cutaneous medicine 9 there are also cardiac-sparing techniques to reduce potential late side effects from breast radiotherapy. 14 despite these significant advances in reducing potential toxicities from radiation therapy, patients continue to frequently have acute skin reactions while undergoing breast radiotherapy. previous studies have sought to examine which patient and treatment factors play a role in acute skin reaction from breast radiation therapy. radiation fractionation schedule, patient position, 3dcrt, imrt, concomitant hormone treatment, and patient-related factors including high bmi, large breast volumes, smoking during treatment, and single nucleotide polymorphisms in genes involved in dna repair pathways have all been examined. increased risk of acute dermatitis was found with standard fractionation schedules, 3d-crt technique compared to imrt, largest breast size, high bmi, and smoking. 10,15-17 across these studies there was significant disagreement on the most significant factors for the development of acute breast radiation dermatitis, likely due to the smaller study number of these retrospective reviews. in our study, bmi, total radiation dose, and radiation fractionation schedule appear to be the most important factors for development of breast radiation dermatitis. unlike current studies available, our study also determined specific thresholds significant for the development of breast dermatitis, including a 1-unit increase in bmi and a 100-cgy increase in dose to the breast for the development of moderate to severe acute dermatitis. in addition, a hypofractionated course of radiation therapy seems to be beneficial for decreasing acute dermatitis risk and would support using this regimen over a standard fractionated course of radiation therapy. though autoimmune disease was not analyzed on multivariate analysis given the smaller sample size of patients, it may be a significant risk factor for the development of radiation dermatitis if a large enough sample size of patients with autoimmune disease can be obtained. understanding when these risk factors affect the development of acute dermatitis may help physicians to counsel the patients who are more likely to develop these skin toxicities. in addition, it may lead physicians to re-examine their treatment approach to help minimize the moderate to severe skin reactions that ultimately could lead to worse cosmetic outcomes in the long-term. finally, individuals at high risk of such toxicity may benefit from additional and earlier skindirected interventions to potentially mitigate acute skin toxicity. conflict of interest disclosures: none. funding: none. acknowledgements: this study was supported by irb# stu00103702. corresponding author: jennifer j. parker, md, phd department of radiation oncology robert h. lurie comprehensive cancer center northwestern university feinberg school of medicine arkes pavilion 676 north saint clair street, suite 1820 chicago, il 60611 312-926-3521 jennifer.parker@northwestern.edu references: skin january 2018 volume 2 issue 1 copyright 2018 the national society for cutaneous medicine 10 1. fisher b, anderson s, bryant j, margolese rg, deutsch m, fisher er, et al. twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. n engl j med. 2002;347:1233-1241. 2. poggi mm, danforth dn, sciuto lc, smith sl, steinberg sm, liewehr dj, et al. eighteen-year results in the treatment of early breast carcinoma with mastectomy versus breast conservation therapy: the national cancer institute randomized trial. cancer. 2003;98:697-702. 3. veronesi u, cascinelli n, mariani l, greco m, saccozzi r, luini a, et al. twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for breast cancer. n engl j med. 2002;347:1227-1232. 4. early breast cancer trialists’ collaborative group (ebctcg). effect of radiotherapy after breastconserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10,801 women in 17 randomised trials. lancet. 2011; 378:1707-1716. 5. wapnir il, dignma jj, fisher b, mamounas ep, anderson sj, julian tb, et al. long-term outcomes of invasive ipsilateral breast tumor recurrences after lumpectomy in nsabp b-17 and b-24 randomized clinical trials for dcis. j natl cancer inst. 2011;103:478-488. 6. early breast cancer trialists’ collaborative group (ebctcg). overview of the randomized trials of radiotherapy in ductal carcinoma in situ of the breast. j natl cancer inst monogr. 2010; 41:162-177. 7. salvo n, barnes e, van draanen j, stacey e, mitera g, breen d, et al. prophylaxis and management of acute radiation-induced skin reactions: a systematic review of literature. curr oncol. 2010;17:94112. 8. schnur jb, love b, scheckner bl, green s, wernicke ag, montgomery gh. a systematic review of patientrated measures of radiodermatitis in breast cancer radiotherapy. am j clin oncol. 2011; 34:529-536. 9. lilla c, ambrosone cb, kropp s, helmbold i, schmezer p, von fournier d, et al. predictive factors for late normal tissue complications following radiotherapy for breast cancer. breast cancer res treat. 2007;106:143-150. 10. pignol jp, olivotto i, rakovitch e, gardner s, sixel k, beckham w, et al. a multicenter randomized trial of breast intensity-modulated radiation therapy to reduce acute radiation dermatitis. j clin oncol. 2008;26:2085-2092. 11. harsolia a, kestin l, grills i, wallace m, jolly s, jones c, et al. intensity-modulated radiotherapy skin january 2018 volume 2 issue 1 copyright 2018 the national society for cutaneous medicine 11 results in significant decrease in clinical toxicities compared with conventional wedge-based breast radiotherapy. int j radiat oncol biol phys. 2007;68:1375-1380. 12. formenti sc, gidea-addeo d, goldberg jd, roses df, guth a, rosenstein bs, et al. phase i-ii trial of prone accelerated intensity modulated radiation therapy to the breast to optimally spare normal tissue. j clin oncol. 2007;25:22362242. 13. haviland, j.s., owen, j.r., dewar, j.a., agrawal, r.k., barrett, j., barrett-lee, p.j., dobbs, h.j., hopwood, p., lawton, p.a., magee, b.j., mills, j., simmons, s., sydenham, m.a., venables, k., bliss, j.m., yarnold, j.r. the uk standardisation of breast radiotherapy (start) trials of radiotherapy hypofractionation for treatment of early breast cancer: 10-year follow-up results of two randomized controlled trials. the lancet oncology. 2013; 14:10861094. 14. register s, takita c, reis i, zhao w, amestoy w, wright, j. deep inspiration breath hold technique for leftsided breast cancer: an analysis of predictors for organ-atrisk sparing. med dosim. 2015;40:89-95. 15. freedman gm, anderson pr, li j, eisenberg df, hanlon al, wang l, et al. intensity modulated radiation therapy (imrt) decreases acute skin toxicity for women receiving radiation for breast cancer. am j clin oncol. 2006;29:66-70. 16. de langhe s, mulliez t, velderman l, remouchamps v, van greveling a, gilsoul m, et al. factors modifying the risk of developing acute skin toxicity after wholebreast intensity modulated radiotherapy. bmc cancer. 2014;14:711-719. 17. kraus-tiefenbacher u, sfintizky a, welzel g, simeonova a, sperk e, siebenlist k, et al. factors of influence on acute skin toxicity of breast cancer patients treated with standard three-dimensional conformal therapy (3d-crt) after breast conserving surgery (bcs). radiation oncology. 2012;7:217225. introduction • psoriasis is a chronic, systemic in� ammatory disease that is associated with signi� cant impairments in quality of life (qol), which may include physical discomfort, pruritus, and emotional distress.1-4 • apremilast is an oral, small-molecule phosphodiesterase 4 inhibitor that has demonstrated ef� cacy and safety vs. placebo (pbo) in the liberate global phase 3b trial in patients with moderate to severe plaque psoriasis.5 • ef� cacy was maintained for up to 104 weeks in patients who continued treatment with apremilast 30 mg twice daily (apr) in the liberate trial.6 • to further understand the clinical pro� le of apr, the effect of long-term apr treatment on patient-reported outcomes assessed at 104 weeks was evaluated in the liberate patient population. methods patients key inclusion criteria • adults ≥18 years of age • chronic plaque psoriasis for ≥12 months • candidates for phototherapy who had no prior exposure to biologics for the treatment of psoriatic arthritis or psoriasis • moderate to severe plaque psoriasis, as de� ned by psoriasis area and severity index (pasi) score ≥12, psoriasis-involved body surface area (bsa) ≥10%, and static physician global assessment (spga) score ≥3 • inadequate response, inability to tolerate, or contraindication to ≥1 conventional systemic agent for the treatment of psoriasis key exclusion criteria • prior treatment with >3 systemic agents for the management of psoriasis • other clinically signi� cant or major uncontrolled diseases • serious infections, including latent, active, or history of incompletely treated tuberculosis study design • liberate consisted of 2 treatment phases: a 16-week randomized, double-blind, pbo-controlled phase and an 88-week apr extension phase for an overall treatment duration of 104 weeks (figure 1). – patients were randomized (1:1:1) to pbo, apr, or etanercept 50 mg once weekly (etn). – at week 16, all patients in the pbo and etn groups switched to apr, and patients in the apr group continued apr. treatment with apr was maintained from weeks 16 to 104 (apr extension phase). figure 1. study design follow-up phase 4 weeks week ‒5 week 16 primary end point week 32 topicals/phototherapy* for non-responders week 104 week 0 apremilast extension phase placebo-controlled phase screening period etanercept 50 mg qw + placebo tablets dose titration apremilast 30 mg bid + placebo injection apremilast 30 mg bid apremilast 30 mg bid apremilast 30 mg bid no dose titration placebo tablets + placebo injection r an d o m iz e (1 :1 :1 ) screening week 52 analysis clinicaltrials.gov: nct01690299 note: liberate was not powered for apr vs. etn comparisons. *starting at week 32, all non-responders (<pasi-50) had the option of adding topical therapies and/or ultraviolet b phototherapy (excluding oral psoralen combined with ultraviolet a) to their treatment regimen. pasi-50=50% or greater reduction from baseline in psoriasis area and severity index score. methods (cont’d) patient-reported assessments • at weeks 16 and 104, the proportion of patients achieving response, de� ned as the minimal clinically important difference (mcid), was evaluated for the following patient-reported outcomes: – dermatology life quality index (dlqi); mcid de� ned as a ≥5-point decrease from baseline in patients with baseline dlqi score >57 – pruritus visual analog scale (vas; 0–100 mm); mcid de� ned as a decrease from baseline ≥20%8 – 36-item short form health survey version 2 (sf-36v2) mental and physical component summary scores (mcs and pcs); both mcids de� ned as an increase of ≥2.5 points from baseline9 – patient health questionnaire-8 (phq-8); mcid de� ned as achievement of score ≤4 (no signi� cant depressive symptoms)10 safety assessments • safety was assessed based on adverse events (aes), vital signs, clinical laboratory assessments, and physical examinations. statistical analysis • achievement of mcid on the dlqi at week 16 and week 104 was a prespeci� ed exploratory end point, whereas achievement of mcid on the pruritus vas, the mcs and pcs, and the phq-8 were post hoc analyses. • all mcid analyses were performed using the modi� ed intent-to-treat (mitt) population, which included all randomized patients who received ≥1 dose of study medication and had an evaluation at baseline and at the speci� ed time point. • end points were analyzed using descriptive statistics, including proportions of patients achieving each end point by treatment group; associated 95% con� dence intervals (cis) were calculated. all data were analyzed as observed, with no imputation for missing values. • the safety population consisted of all patients who were randomized and received ≥1 dose of study medication. descriptive statistics were used for summaries of treatment-emergent aes and other safety assessments. results patients • the mitt population consisted of 250 patients (pbo, n=84; apr, n=83; etn, n=83). • patient demographics and baseline disease characteristics were generally comparable between treatment groups (table 1). table 1. patient demographics and baseline disease characteristics pbo n=84 apr n=83 etn n=83 age, mean (sd), years 43.4 (14.9) 46.0 (13.6) 47.0 (14.1) male, n (%) 59 (70.2) 49 (59.0) 49 (59.0) white, n (%) 80 (95.2) 79 (95.2) 75 (90.4) body mass index, mean (sd), kg/m2 29.6 (6.6) 29.1 (5.9) 29.9 (6.9) weight, mean (sd), kg 89.5 (23.1) 88.5 (19.8) 88.1 (20.5) duration of psoriasis, mean (sd), years 16.6 (12.1) 19.7 (12.7) 18.1 (11.7) pasi score (0–72), mean (sd) 19.4 (6.8) 19.3 (7.0) 20.3 (7.9) pasi score >20, n (%) 32 (38.1) 28 (33.7) 34 (41.0) body surface area, mean (sd), % 27.3 (16.1) 27.1 (15.6) 28.4 (15.7) body surface area >20%, n (%) 42 (50.0) 45 (54.2) 47 (56.6) spga of 4 (severe), n (%) 23 (27.4) 17 (20.5) 13 (15.7) prior use of conventional systemic medications, n (%) 70 (83.3) 66 (79.5) 58 (69.9) vas scores* (0–100 mm), mean (sd), mm pruritus 62.5 (22.7) 62.6 (25.7) 57.2 (27.7) skin discomfort/pain 43.9 (31.2) 51.8 (30.8) 47.3 (32.8) patient global assessment of psoriasis disease activity, mean (sd) 53.6 (21.6) 60.9 (24.6) 55.6 (24.2) dlqi score* (0–30), mean (sd) 11.4 (6.3) 13.6 (6.7) 12.5 (7.0) phq-8* (0–24), mean (sd) 4.8 (4.4) 5.8 (5.0) 5.0 (5.2) sf-36v2,* mean (sd) mcs (0–100) 44.3 (11.0) 42.8 (12.6) 45.6 (10.8) pcs (0–100) 50.8 (7.8) 46.1 (9.0) 46.2 (9.1) *n=number of patients randomized; number of patients with scores available at baseline differs from randomized n for the following parameters: vas (pbo, n=81; apr, n=79; etn, n=78); dlqi and sf-36v2 mcs and pcs (pbo, n=81; apr, n=81; etn, n=80); phq-8 (pbo, n=81; apr, n=82; etn, n=80). results (cont’d) patient-reported outcomes dlqi mcid achievement: week 16 and week 104 • at week 16, a higher proportion of patients in the apr and etn groups achieved dlqi mcid compared with the pbo group; response was generally maintained at week 104 among patients who continued apr or who were switched at week 16 from pbo to apr (pbo/apr) or from etn to apr (etn/apr) and remained on apr at week 104 (figure 2). figure 2. achievement of dlqi mcid at week 16 and week 104 59 70 75 69 80 68 0 20 40 60 80 100 n/m= pa ti en ts a ch ie vi ng d lq i m c id ( % ) pbo/apr apr/apr etn/aprpbo apr etn 35/59 28/40 48/64 25/36 52/65 27/40 week 16 week 16week 16week 104 week 104week 104 includes patients in the mitt population with a dlqi score >5 at baseline, with a value at baseline and at the speci� ed time point. mcid=≥5-point decrease from baseline; n/m=number of patients achieving dlqi mcid/number of patients with evaluable data at the time point. pruritus vas mcid achievement at week 16 and week 104 • at week 16, a higher proportion of patients in the apr and etn groups achieved pruritus vas mcid compared with the pbo group. response was maintained at week 104 in the apr/apr group and in patients who switched at week 16 from etn or pbo to apr (figure 3). figure 3. achievement of pruritus vas mcid at week 16 and week 104 60 77 87 80 89 80 0 20 40 60 80 100 n/m= pa ti en ts a ch ie vi ng p ru ri tu s va s m c id ( % ) pbo/apr apr/apr etn/aprpbo apr etn 42/70 37/48 60/69 32/40 67/75 37/46 week 16 week 16week 16week 104 week 104week 104 includes patients in the mitt population with a value at baseline and at the speci� ed time point. mcid=improvement ≥20% from baseline; n/m=number of patients achieving pruritus improvement ≥20% from baseline/number of patients with evaluable data at the time point. mcs and pcs mcid achievement at week 16 and week 104 • the proportions of patients achieving the mcid for the mcs were generally similar among the treatment groups at week 16. at week 104, mcs response was maintained in pbo/apr patients and was comparable between apr/apr and etn/apr patients at week 104 (figure 4a). • at week 16, the proportion of patients achieving pcs mcid was lowest in the pbo group. at week 104, pcs response was comparable between the apr/apr and etn/apr groups and remained lower in the pbo/apr group (figure 4b). results (cont’d) figure 4. achievement of mcid on mcs (a) and pcs (b) at week 16 and week 104 51 54 59 45 53 45 0 40 20 60 80 100 n/m= pa ti en ts a ch ie vi ng sf -3 6v 2 m c s m c id ( % ) pbo/apr apr/apr mcs mcida. pcs mcidb. etn/aprpbo apr etn 36/70 26/48 42/71 18/40 41/77 21/47 week 16 week 16week 16week 104 week 104week 104 29 31 41 48 60 49 0 40 20 60 80 100 n/m= pa ti en ts a ch ie vi ng sf -3 6v 2 pc s m c id ( % ) pbo/apr apr/apr etn/aprpbo apr etn 20/70 15/48 29/71 19/40 46/77 23/47 week 16 week 16week 16week 104 week 104week 104 includes patients in the mitt population with a baseline value and a value at the speci� ed time point. mcid=improvement ≥2.5 from baseline; n/m=number of patients achieving sf-36v2 mcs or pcs mcid/number of patients with evaluable data at the time point. phq-8 mcid achievement • at week 16 and week 104, proportions of patients achieving the mcid for phq-8 (i.e., score ≤4 [no signi� cant depressive symptoms]) were generally similar among the treatment groups; response was maintained at week 104 in the apr/apr group and in patients who switched at week 16 from etn or pbo to apr (figure 5). figure 5. achievement of phq-8 mcid at week 16 and week 104 33 40 34 33 43 49 0 20 40 60 80 100 n/m= pa ti en ts a ch ie vi ng p h q -8 m c id ( % ) pbo/apr apr/apr etn/aprpbo apr etn 23/70 19/48 24/71 13/40 32/75 23/47 week 16 week 16week 16week 104 week 104week 104 includes patients in the mitt population with a baseline value and a value at the speci� ed time point. mcid=score ≤4; n/m=number of patients achieving phq-8 score ≤4/number of patients with evaluable data at the time point. safety • during the pbo-controlled period (weeks 0 to 16), aes occurring in ≥5% of patients in any treatment group were diarrhea, nausea, upper respiratory tract infection, nasopharyngitis, headache, and tension headache (table 2). • during the apr extension phase (weeks 16 to 104), aes that occurred in ≥5% of patients in any treatment group included those observed during the pbo-controlled period as well as arthralgia, rebound psoriasis, pain in extremity, bronchitis, psoriasis, and sinusitis. • most aes were mild or moderate in severity, did not increase with prolonged apr exposure, and did not lead to study discontinuation. results (cont’d) table 2. summary of safety during weeks 0 to 165 pbo-controlled phase weeks 0 to 16* pbo n=84 apr n=83 etn n=83 patients, n (%)§ ≥1 ae 45 (53.6) 59 (71.1) 44 (53.0) ≥1 serious ae 0 (0.0) 3 (3.6) 2 (2.4) ≥1 severe ae 2 (2.4) 3 (3.6) 3 (3.6) ae leading to drug withdrawal 2 (2.4) 3 (3.6) 2 (2.4) aes reported by ≥5% of patients in any treatment group diarrhea 3 (3.6) 9 (10.8) 1 (1.2) nausea 1 (1.2) 9 (10.8) 4 (4.8) upper respiratory tract infection 2 (2.4) 6 (7.2) 2 (2.4) nasopharyngitis 8 (9.5) 4 (4.8) 8 (9.6) headache 3 (3.6) 11 (13.3) 5 (6.0) tension headache 4 (4.8) 5 (6.0) 3 (3.6) *each patient is counted once for each applicable category. §safety population. • no clinically meaningful changes were reported in laboratory parameters. • no cases of tuberculosis (new or reactivation) were reported during the trial. conclusions • in biologic-naive patients with moderate to severe psoriasis, improvements in patient-reported outcomes, including qol and pruritus, were generally maintained with continued apr treatment up to 104 weeks. • aes were consistent with the known safety pro� le of apr. references 1. reich k. j eur acad dermatol venereol. 2012;26(suppl 2):3-11. 2. owczarek k, jaworski m. postepy dermatologii i alergologii. 2016;33:102-108. 3. meyer n, et al. j eur acad dermatol venereol. 2010;24:1075-1082. 4. reich a, et al. acta derm venereol. 2010;90:257-263. 5. reich k, et al. j eur acad dermatol venereol. 2017;31:507-517. 6. reich k, et al. safety and ef� cacy of apremilast through 104 weeks in patients with moderate to severe psoriasis who continued on apremilast or switched from etanercept treatment in the liberate study. presented at: annual meeting of the american academy of dermatology; march 3-7, 2017; orlando, fl. 7. basra mk, et al. dermatology. 2015;230:27-33. 8. reich a, et al. acta derm venereol. 2013;93:609-610 [abstract il26]. 9. strand v, et al. health qual life outcomes. 2013;11:82. 10. kroenke k, et al. j affect disord. 2009;114:163-173. acknowledgments the authors acknowledge � nancial support for this study from celgene corporation. the authors received editorial support in the preparation of this poster from amy shaberman, phd, of peloton advantage, llc, parsippany, nj, usa, funded by celgene corporation, summit, nj, usa. the authors, however, directed and are fully responsible for all content and editorial decisions for this poster. correspondence shane chapman – michael.shane.chapman@hitchcock.org disclosures sc: nothing to disclose. jc: celgene corporation – employment. sm: nothing to disclose. presented at: the winter clinical dermatology conference – hawaii; january 12–17, 2018; maui, hi. sustained improvement in patient-reported outcomes with continued apremilast treatment over 104 weeks in patients with moderate to severe psoriasis shane chapman, md1; joshua cirulli, pharmd2; sandy mcbride, md3 1dartmouth–hitchcock medical center, lebanon, nh, usa; 2celgene corporation, summit, nj, usa; 3royal free london nhs foundation trust, london, uk ● atopic dermatitis (ad) is a chronic inflammatory skin disease affecting 2.1−4.9% of adults across north america, europe, and japan1 ● ad is characterized by excessive dryness, intense itching, inflamed skin, and open sores or oozing2-3 and has a significant impact on quality of life due to itch, sleep interference, and psychological distress4 ● tralokinumab is a fully human monoclonal antibody which neutralizes interleukin-13, a key driver of the chronic inflammation underlying moderate-to-severe ad5-9 ● primary analysis of the phase 3 trials (ecztra 1 [nct03131648] and ecztra 2 [nct03160885]) demonstrated superiority of tralokinumab 300 mg every 2 weeks compared with placebo in all primary and secondary endpoints of the initial 16-week treatment period. superiority of tralokinumab for the primary endpoint of investigator’s global assessment (iga) 0/1 was more pronounced in ecztra 2 than in ecztra 1 ● ecztra 1 and ecztra 2 followed an identical design, but recruited patients from different countries across europe, north america, asia, and oceania. the randomization procedure stratified patients by geographical region and baseline iga score (moderate or severe). hence, an imbalance in baseline characteristics may be present within countries a b 0 10 20 30 40 50 60 70 80 90 100 north america (usa) (n=198) europe (n=477) asia (japan) (n=127) all subjects (n=802) p a ti e n ts , % 0 10 20 30 40 50 60 70 80 90 100 north america (usa & canada) (n=361) europe (n=234) asia (korea) (n=78) australia (n=121) all subjects (n=794) p a ti e n ts , % ecztra 2 ecztra 1 moderate (iga=3) severe (iga=4) moderate (iga=3) severe (iga=4) figure 2. proportion of patients with severe (baseline iga=4) and moderate (iga=3) ad by region in (a) ecztra 1 and (b) ecztra 2 a b 0 10 20 30 40 50 north america (usa) (n=198) europe (n=477) asia (japan) (n=127) all subjects (n=802) m e a n b a se lin e e a s i 0 10 20 30 40 50 north america (usa & canada) (n=361) europe (n=234) asia (korea) (n=78) australia (n=121) all subjects (n=794) m e a n b a se lin e e a s i ecztra 2 ecztra 1 moderate (iga=3) severe (iga=4) moderate (iga=3) severe (iga=4) figure 3. mean baseline easi scores of patients by region and baseline iga in (a) ecztra 1 and (b) ecztra 2 a 0 20 40 60 80 100 wet wraps phototherapy antibiotics other immunosuppressant azathioprine methotrexate cyclosporine mycophenolate systemic steroids calcineurin inhibitors topical corticosteroid any previous treatment patients, % p ri o r a d t re a tm e n t north america (n=361) europe (n=234) asia (korea) (n=78) australia (n=121) ecztra 1 wet wraps phototherapy antibiotics other immunosuppressant azathioprine methotrexate cyclosporine mycophenolate systemic steroids calcineurin inhibitors topical corticosteroid any previous treatment p ri o r a d t re a tm e n t north america (n=198) europe (n=477) asia (japan) (n=127) b ecztra 2 0 20 40 60 80 100 patients, % axis axis figure 4. prior ad treatments in all randomized patients by region in (a) ecztra 1 and (b) ecztra 2 a b 0 20 40 60 80 100 p a ti e n ts , % 0 20 40 60 80 100 p a ti e n ts , % ecztra 2 ecztra 1 topical corticosteroid potency topical corticosteroid potency 37.4% 34.8% 15.2% 52.0% 45.7% 23.3% 50.1% 11.1% 12.8% 21.5% 49.6% 22.3%20.9% 33.8% 36.3% 19.9% 35.7% 29.9% 11.1% 23.1% 46.2% 10.3% north america (n=198) europe (n=477) asia (japan) (n=127) north america (n=361) europe (n=234) asia (korea) (n=78) australia (n=121) low moderate unknown high ultra high low moderate unknown high ultra high figure 5. potency of prior tcs used in all randomized patients in (a) ecztra 1 and (b) ecztra 2 2020 fall clinical dermatology conference, october 29-november 1, 2020, live virtual meeting ● in this post hoc analysis of the ecztra 1 and ecztra 2 studies, regional differences were observed in disease severity and prior ad treatment, despite identical inclusion criteria ● japan and australia enrolled a similarly high proportion of patients with severe ad (iga-4); however, australia had the highest levels of prior medication use, compared with low use of medications (including systemic immunosuppressants) in japan, most likely due to regional differences in ad treatment guidelines ● regional differences in standard of care, in addition to differential assessment of study outcomes may, in part, explain the differences in therapeutic responses observed between ecztra 1 and ecztra 2. these analyses highlight the importance of stratification by region in the randomization procedure as performed in these trials conclusions characteristic ecztra 1 (n=802) ecztra 2 (n=794) mean age, years (sd) 38.8 (14.1) 36.7 (14.6) male, % 59.1 59.6 severe disease (iga-4), % 50.7 48.7 mean easi (sd) 32.4 (13.8) 32.2 (14.2) mean scorad (sd) 70.6 (12.9) 70.1 (13.1) mean dlqi (sd) 16.9 (7.0) 17.7 (7.1) mean weekly average worst daily pruritus nrs (sd) 7.7 (1.4) 7.9 (1.4) mean duration of ad, years (sd) 28.3 (14.7) 28.1 (15.6) mean bsa involvement with ad, % (sd) 53.1 (24.5) 52.7 (25.4) table 1. demographics and baseline characteristics of all randomized patients dlqi, dermatology life quality index. patient demographics and ad severity at baseline ● in total, 802 and 794 patients were randomized in ecztra 1 and 2, respectively. overall the demographic and disease characteristics at baseline were similar across the trials (table 1) ● patients had a long mean duration of ad (28.3/28.1 years) and high body surface area (bsa) involvement (53.1/52.7%) study design and patients ● ecztra 1 and ecztra 2 were identically designed, multinational, double-blind, randomized, placebo-controlled, 52-week clinical trials of tralokinumab monotherapy in patients with moderate-to-severe ad — in ecztra 1, patients were enrolled from europe (germany, france, spain), north america (usa), and asia (japan) — in ecztra 2, patients were enrolled from europe (uk, italy, denmark, poland, and russia), north america (usa and canada), asia (korea), and australia ● based on the inclusion criteria, eligible patients were 18 years of age, with a confirmed diagnosis of ad for 1 year, eczema area and severity index (easi) score of 16, iga 3, pruritus numeric rating scale (nrs) 4, and were candidates for systemic therapy due to a recent (within 1 year) history of inadequate response or intolerance to topical treatment ● before treatment, patients underwent a washout period of 2 weeks for topical treatments including topical corticosteroids (tcs), 4 weeks for systemic medications, and 6 weeks for phototherapy (figure 1) references 1. barbarot s et al. allergy 2018; 73: 1284−1293. 2. nutten s. ann nutr metab 2015; 66(suppl 1): 8–16. 3. weidinger s, novak n. lancet 2016; 387: 1109–1122. 4. silverberg ji et al. ann allergy asthma immunol 2018; 121: 340–347. 5. szegedi k et al. j eur acad dermatol venereol 2015; 29: 2136–2144. 6. popovic b et al. j mol biol 2017; 429: 208–219. 7. furue k et al. immunology 2019; 158: 281–286. 8. tsoi lc et al. j invest dermatol 2019; 139: 1480–1489. 9. bieber t. allergy 2020; 75: 54–62. disclosures eric simpson reports grants and/or personal fees from abbvie, boehringer ingelheim, celgene, dermavant, dermira, forte bio, galderma, incyte, kyowa hakko kirin, leo pharma, lilly, medimmune, menlo therapeutics, merck, novartis, ortho dermatologics, pfizer, pierre fabre dermo cosmetique, regeneron, sanofi, tioga, and valeant. thomas werfel has received honoraria for invited talks or scientific advice and research grants from astellas, galderma, janssen/jnj, leo pharma, lilly, novartis, pfizer, and sanofi/regeneron. thomas bieber has been a lecturer and/or consultant for abbvie, almiral, anaptysbio, arena, asana biosciences, astellas, bioversys, boehringer ingelheim, celgene, daiichi sankyo, davos biosciences, dermavant/roivant, dermtreat, ds pharma, evaxion, flx bio, galapagos/morphosys, galderma, glaxosmithkline, glenmark, incyte, kymab, leo pharma, lilly, l´oréal, menlo therapeutics, novartis, pfizer, pierre fabre, sanofi/regeneron, ucb, and vectans. louise abildgaard steffensen, alexandra kuznetsova, and marie louise østerdal are employees of leo pharma. hidehisa saeki is an advisor to leo pharma. the tralokinumab ecztra 1 and 2 studies were sponsored by leo pharma ● of the patients with severe ad (iga-4) at baseline, higher mean baseline easi was observed in japan (46.3 and australia (48.0), compared with europe (37.9/40.9), north america (37.6/34.9), and korea (42.3) (figure 3) prior treatment for ad ● the trial population was heavily pretreated for ad. almost all patients across all regions had received prior tcs (96−100%) (figure 4) — the proportion of patients who had received ultra-high potency tcs was highest in japan, whereas in korea the majority of tcs used was of low and moderate potency (figure 5) ● prior systemic steroid treatment was highest in australia (80.2%) and korea (79.5%) ● there was high variability in prior use of systemic immunosuppressants. cyclosporine was the most commonly used systemic immunosuppressant, used by 40% of patients in japan, europe, korea, and australia. use of mycophenolate, methotrexate, and azathioprine was less common, in ,22% of patients, except in australia where methotrexate and azathioprine were used by 33.9% and 28.9%, respectively ● more patients in europe and australia had received phototherapy for ad compared with asia and north america, and use of wet wraps was also higher in australia compared with other regions tralokinumab 300 mg q2w tralokinumab 300 mg q2w placebo q2w placebo q2w tralokinumab 300 mg q4w alternating with placebo open-label treatment tralokinumab 300 mg q2w optional tcs and optional home use placebo q2w 3:1 randomization washout of tcs and other ad medication 300 mg q2w after initial loading dose (600 mg) patient with clinical response of iga-0/1 or easi-75 2:2:1 randomization ecztra 1 (n=603) ecztra 2 (n=593) ecztra 1 (n=199) ecztra 2 (n=201) screening initial treatment maintenance treatment safety follow-up 66 weeks52 weeks16 weeks0-6 weeks key inclusion criteria • diagnosis of ad for �1 year • bsa involvement �10% • easi score �12 at screening and 16 at baseline • iga score �3 at screening and at baseline • worst daily pruritus nrs average score ≥4 prior to baseline • patients not achieving iga-0/1 or easi-75 at week 16 • patients transferred from maintenance treatment secondary endpoints • reduction of worst daily pruritus nrs (weekly average) �4 from baseline to week 16 • change in scoring atopic dermatitis (scorad) from baseline to week 16 • change in dlqi score from baseline to week 16 maintenance endpoints • iga-0/1 at week 52 • easi-75 at week 52 primary endpoints • iga-0/1 at week 16 • easi-75 at week 16 figure 1. ecztra 1 and ecztra 2 trial design introduction results methods objective ● the objective of this post hoc analysis was to evaluate whether there were meaningful regional differences in baseline characteristics and prior ad treatment in the large cohort of patients with moderate-to-severe ad from the phase 3 tralokinumab studies (ecztra 1 and ecztra 2) tralokinumab monotherapy in adult patients with moderate-to-severe atopic dermatitis: regional differences in baseline disease characteristics and prior treatment in the ecztra 1 and ecztra 2 trials 1department of dermatology, oregon health & science university, portland, or, usa; 2department of dermatology and allergy, hannover medical school, hannover, germany; 3department of dermatology and allergy, university medical center, bonn, germany; 4leo pharma a/s, ballerup, denmark; 5department of dermatology, nippon medical school, tokyo, japan eric simpson,1 thomas werfel,2 thomas bieber,3 louise abildgaard steffensen,4 alexandra kuznetsova,4 marie louise østerdal,4 hidehisa saeki5 post hoc analysis ● this analysis compared patient demographics, disease characteristics, and prior use of ad treatments in all randomized patients by region in the ecztra 1 and ecztra 2 trials ● the proportion of patients with severe ad (iga-4) was 50.7% and 48.7% for the overall study populations in ecztra 1 and 2, respectively. japan (66.1%) and australia (63.6%) had the highest proportions of patients with severe ad (iga-4) compared with europe (52.6/51.3%), north america (36.4/43.2%), and korea (43.6%) (figure 2) skin july idr 1134 proof returned skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 333 in-depth review treatment of pyodermatitis-pyostomatitis vegetans: a systematic review and meta-analysis landon k. hobbs, bs1*, alina g. zufall, ba1*, shadi khalil, md, phd2, richard h. flowers, md1 1department of dermatology, university of virginia school of medicine, charlottesville, va 2department of dermatology, university of california san diego, san diego, ca *contributed equally as first authors pyodermatitis-pyostomatitis vegetans is a rare mucocutaneous disorder often associated with inflammatory bowel disease (ibd) that can be extremely difficult to treat. due to is rarity, no standardized trials exist comparing the efficacy of different medications, and recommendations for treatment of this disease are limited and not evidence-based. pyodermatitis vegetans (pdv) was first described by the french dermatologist francois hallopeau in 1898 as a distinct disease of vegetating plaques of the skin which he termed “pyodermite vegetante.”1 in 1949, mccarthy described three cases of pdv with mucosal-dominant disease as “pyostomatitis vegetans.”2 clinically, pdv is abstract background: pyodermatitis-pyostomatitis vegetans (pdv-psv) is a rare muco-cutaneous disorder characterized by vegetating and pustular plaques and is often associated with inflammatory bowel disease (ibd). the purpose of this study was to systematically identify and analyze reports of pdv-psv to determine the most effective treatment. methods: reports of pdv-psv were identified using the ovid-medline database from inception through november 2019. publications were excluded if no new patient case was included, if there was not clinical and histological evidence of pdv, psv, or pdv-psv, or if no treatment was discussed. results: the final sample was comprised of 74 publications plus an additional patient from the authors’ institution, corresponding to 95 total patients. the basis of the review and analysis is limited to case reports and case series, which likely only report the cases with positive outcomes. statistical analysis revealed that oral corticosteroids (ocs), 6-mercaptopurine/azathioprine, oral calcineurin inhibitors (ocni), 5-aminosalicylic-acid (5-asa), and biologics (bio) were the most effective treatments for pdvpsv. topical medications, colchicine, oral dapsone, and other antibiotics were ineffective treatments, with topical medications being the least effective option. when ocs are used, they work best when used as initial treatment to induce remission. 5-asa and bio are most effective when used as maintenance therapies after initial remission. conclusions: thus, first line therapy for pdv-psv should begin with ocs with transition to steroidsparing agents including ocni, bio, and 5-asa if indicated. introduction skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 334 characterized by erythematous pustules that become exudative vegetative plaques with well-defined elevated borders.3 pyostomatitis-vegetans (psv) similarly presents with sterile pustules on mucosal sites which erode and coalesce into “snail track” ulcers.4 histological analysis of these lesions reveals eosinophilic or neutrophilic microabscesses and infiltrates, epidermal hyperplasia and often focal acantholysis.1,3,5 the spectrum of disease is referred to as pyodermatitis-pyostomatitis vegetans (pdvpsv), with patients presenting with cutaneous symptoms only, mucosal symptoms only, or both cutaneous and mucosal symptoms. since 1949, pdv-psv has been documented in association with ibd in 80% of cases.1,5,6 treatment is often directed at underlying ibd, though cutaneous and mucosal disease can prove refractory. the purpose of this review was to determine the most effective treatment options for pdvpsv based on the success of medications used for patients with pdv-psv found in the literature. the demographics of this population are presented, as well as the medications attempted for treatment. medications are compared to determine which are most effective for the treatment of pdv-psv. search strategy and inclusion criteria a systematic review was conducted up to november 2019, using the search terms “pyostomatitis vegetans” and “pyodermatitis vegetans” in the pubmed/medline database. all reports were analyzed by two independent reviewers to determine which met inclusion criteria. review papers were used to find any reports missed in the initial literature search. reports were included in the review if there was a new patient case, clinical and histological evidence of pdv, psv, or pdvpsv, and treatment was discussed. a diagnosis of pdv-psv was confirmed by one dermatologist based on the clinical and histological description of pdv-psv in each report. the exclusion criteria included any report that did not meet the above criteria, which included all review papers, reports without evidence of pdv-psv, or those with cases that did not discuss treatment options. an additional case from the authors’ institution was also included for metaanalysis. data extraction and preparation using the prisma guidelines for extracting and assessing data, data from each paper was collected by two independent reviewers and is summarized in table 1, along with the ratings of the quality of evidence of each paper. no methods were used to assess the risk of bias, as this review and analysis consists only of case reports and case series. data collected included patient demographics, including sex, age, and ethnicity, presence and type of concomitant inflammatory bowel disease, histological description of pdv-psv (including immunofluorescence results), complete blood count results prior to initiating treatment (including presence of eosinophilia), inflammatory markers (erythrocyte sedimentation rate (esr) or creactive protein (crp)) prior to initiating treatment, and all medications attempted with associated response. treatment responses were separated into three categories depending on the type of response: partial response, complete response, and no response. partial response was defined as incomplete resolution of lesions, with the disease described as: “relapsing intermittently,” “having slight clinical improvement,” methods skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 335 table 1. summary of findings in 95 reported cases report rating of qoe demographic ibd pdv/ psv response to treatment no response partial response cr-i cr-m cr-d abellaneda 20117 5 35m, spanish uc pdvpsv aza, mtx, dap, col, ret, 5-asa, msc ocs aza + 5-asa ahn 20048 5 33f, korean uc pdvpsv dap, col, osc dap, col, osc 5-asa al-rimawi 19989 5 7m uc psv ocs, 5-asa, chl 5f chronic colitis psv t-cs/cni, ocs atarbashi-moghadam 201610 5 39f cd psv 5-asa, aza ayangco 200211 5 22f, white cd psv t-cs/cni 5-asa ballo 198912 5 39f uc psv abx, t-cs/cni, msc ocs 5-asa bens 200313 5 35f cd psv bio mtx bertlich 201914 5 51f uc pdvpsv aza + ocs + tcs/cni bio, ocs, tcs/cni bianchi 20014 5 48f uc pdv abx 5-asa brinkmeier 200115 5 32f, white none pdvpsv dap, 5-asa ocs, tcs/cni, ocs + ret, ocs + ocni calobrisi 199516 5 65m, white uc psv t-cs/cni total colectomy canpolat 201117 5 64m uc pdv ocs, abx 5-asa carvalho 201618 5 79f none pdv abx + ocs cataldo 198119 5 48m, white cd psv t-cs/cni ocs chan 199120 5 23m, white uc psv fes, tcs/cni, ocs, abx 5-asa 17f, white uc psv 5-asa, tcs/cni, fes chaudhry 199921 5 63m uc psv t-cs/cni, abx clark 20163 4 22f uc psv 5-asa, tcs/cni 30m uc pdvpsv ocs, dap, aza, nys, ptr 29m cd psv ocs, dap skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 336 54m cd psv ocs, t-cs/cni, dap, ocni, mm bio 44f uc pdvpsv ocs, tcs/cni, ptr 21m uc pdvpsv dap, tcs/cni 58m cd pdvpsv ocs, t-cs/cni, dap, msc dodd 201722 5 30f cd pdvpsv bio, aza ocs, tcs/cni bio + dap dupuis 201623 5 48m colitis pdvpsv ocs ficarra 199324 5 45f, italian cd pdvpsv zinc ocs forman 196525 5 45f uc pdvpsv acth, abx 44f uc pdvpsv dap dap abx, tcs/cni gonzalez-moles 200826 5 84f none psv t-cs/cni + nys hansen 198327 5 37m, white uc psv ocs ocs + 5-asa harish 200628 5 35m uc pdv ocs 5-asa healy 199429 5 27m, white uc psv dap, ocs, tcs/cni, aza 5-asa 24f, white none psv chl kajihara 201330 5 78m none pdv ocs + tcs/cni + col ocs + col kalman 201331 5 41f cd psv ocs bio khader 201632 5 21m uc pdv ocs kim 201533 5 27m cd pdvpsv col; osc, dap (high dose) ocs, dap (low dose) kitayama 201034 5 51f, japanese uc pdvpsv ocni, ocs, aza 5-asa knapp 201635 5 10m uc psv abx aza ocs t-cs/cni + aza ko 200936 5 47m none pdvpsv abx, t-cs/cni ocs (high dose) ocs (low dose) 24f none pdvpsv ocs ocs konstantopoulou 200537 5 19m uc pdvpsv abx, t-cs/cni dap ocs + abx leibovitch 200538 5 29m uc pdvpsv abx ocs, tcs/cni 5-asa, ocs skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 337 li 201839 5 25m none pdvpsv ocs 5-asa lopez 201240 5 35m uc pdvpsv msc t-cs/cni, nys, 5-asa lourenco 201041 5 63f uc psv ocs, dap maseda 201742 5 49m cd pdv abx markiewicz 200743 5 30m, white uc psv 5-asa marks 196244 5 20m uc pdvpsv abx, dap abx ocs, acth matias 201145 5 47f none pdv abx ocs (low dose) + dap ocs (higher dose) mccarthy 19632 5 27m, white uc psv t-cs/cni mehravaran 19975 5 43f none pdvpsv ocs+aza ocs merkourea 201346 5 58m cd psv 5-asa (“low dose”) mesquita 201247 5 12m none pdvpsv ocs + aza dap mijandrusic-sincic 201048 5 23f cd psv bio 32f uc psv aza mizukami 201949 5 29f uc psv ocs dap molnar 201150 5 16m cd psv ocs, aza+bio moloney 201151 5 50f uc pdvpsv dap dap + aza + 5-asa naish 197052 5 26m, black uc psv ocs nayak 201753 5 33f uc pdvpsv ocs ocs neville 198554 5 47f, black cd psv ocs 5-asa + ocs nico 201255 4 63f uc psv ocs ocs 33m colitis psv ocs t-cs/cni 33f uc psv ocs 34m uc psv ocs niezgoda 201856 5 69m uc psv ocs + ocni nigen 200357 5 22f none pdvpsv dap t-cs/cni, abx ocs 57f none pdvpsv abx ocs o'hagan 199858 5 65f none pdvpsv ocs t-cs/cni + aza pazheri 201059 5 15f cd psv t-cs/cni peuvrel 200860 5 28m none psv ocs ocs ruiz-roca 200561 5 51f uc psv abx, t-cs/cni saghafi 201162 5 30f none psv ocs skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 338 shah 201363 5 63m uc psv dap soriano 199964 5 49m, white uc pdvpsv 5-asa, tcs/cni t-cs/cni + 5asa 5-asa stingeni 201565 5 17m uc psv ocs aza storwick 199466 5 42f uc pdvpsv ocs t-cs/cni, abx thornhill 199267 5 26f, white uc psv ocs + 5-asa dap 51m, white none psv ocs abx + dap 33f, greek none pdvpsv ocs abx, dap, aza tursi 201668 5 42f uc psv ocs, dap bio, abx uzuncakmak 201569 5 16m uc pdv ocs, abx van hale 198570 5 23f uc pdvpsv abx, dap, msc ocs, tcs/cni colectomy 24f uc pdvpsv aza t-cs/cni, iv alb, msc dap wang 201371 5 42f uc pdvpsv alb, ocs werchniak 200572 5 30f uc pdv nys t-cs/cni 5-asa wolz 201373 5 21m, white uc pdvpsv t-cs/cni + dap dap 58m, white cd pdvpsv ocs + dap dap wray 198474 5 58m, white uc psv 5-asa ocs t-cs/cni 52m, white none psv t-cs/cni + 5asa yasuda 200875 5 37m uc pdvpsv t-cs/cni total colectomy t-cs/cni index patient 5 51f, hispanic uc pdvpsv mtx, t-cs/cni, abx, msc ret, mm, abx, tcs/cni dap, ocs, abx empty box: not mentioned or specified in primary paper abbreviations: 5-asa, sulfasalazine/sulphasalazine, aminosalicylates, mesalamine; abx, antibiotics (piperacillin4, metronidazole4,17,37,41, amoxicillin clavulanate17,18,38,67, dicloxacillin38, ciprofloxacin41,42, clarithromycin42, vancomycin37, penicillin44, di-iodohydroxyquinoline44, streptomycin44, doxycycline61, sulfonamides25,67, and tetracycline20,21); acth, adrenocorticotropic hormone; alb, albumin; aza, azathioprine, mercaptopurine; bio, biologic (infliximab3,14,22,31,41, adalimumab22,48,50, and golimumab68); cd, crohn’s disease; chl, chlorhexidine mouthwash; col, colchicine; cr-d, complete response-discontinuation; cr-i, complete response—initial; cr-m, complete response— maintenance; dap, dapsone; f, female; fes, ferrous sulfate; m, male; mm, mycophenolate mofetil; msc, miscellaneous (intravenous immunoglobulin7, aurothiomalate7, acyclovir12, ketoconazole3, “antifungals40,” topical imiquimod, vitamin therapy70, diphenhydramine elixer70, and viscous lidocaine70); mtx, methotrexate; nys, nystatin; ocs, systemic corticosteroids; ocni, oral calcineurin inhibitors; ptr, petrolatum; qoe, quality of evidence; ret, retinoids; t-cs/cni, topical corticosteroids or topical calcineurin inhibitor; uc, ulcerative colitis. skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 339 “improved but still present,” “regressed,” or “still mildly active.” cases with complete response required evidence of good control of the disease after initiating or discontinuing the medication. response of the disease to treatment in these cases was described as: “having marked or significant improvement,” “resolution,” “relief,” or being “wellcontrolled.” complete response was further subdivided into three categories: resolution while on—initial (cr-i); response while on— maintenance (cr-m); and remission after discontinuation (cr-d). drugs were split into initial and maintenance categories if one drug resulted in the resolution of lesions (cr-i) then a second drug was added immediately after to maintain remission (cr-m). if a treatment resulted in resolution of pdv-psv while on the drug, but lesions recurred after discontinuation, then this medication was considered cr-i. a treatment required only intermittently for relapse control resulting in complete control was also considered cr-i. drugs directed at underlying ibd were generally included in the cr-m category, as patients often remained on these medications indefinitely. medications that resulted in sustained clearance of pdv-psv after their discontinuation were considered cr-d. medications were included in this category if the authors stated that there was “complete remission” after drug discontinuation or sustained clearance was noted after follow-up, with follow-up times ranging from 15 days to 20 years (mean= 26.4 months, median=12 months). the medications used to treat pdv-psv were divided as follows: oral corticosteroids (ocs), topical medications (t-cs/cni), colchicine (col), azathioprine/6mercaptopurine (aza), 5-aminosalicylic-acid (5-asa) derivatives, oral calcineurin inhibitors (ocni: tacrolimus and cyclosporine), biologics, oral dapsone (dap), other antibiotics (abx), and miscellaneous medications (msc). topical corticosteroids and topical tacrolimus were combined into a topical medications category (t-cs/cni) due to their limited systemic effects. oral dapsone and other antibiotics were separated because dapsone is most commonly used for its anti-neutrophilic and general antiinflammatory mechanisms. other antibiotics used to treat pdv-psv included: piperacillin4, metronidazole4,17,37,41, amoxicillin clavu-lanate17,18,38,67, dicloxacillin38, cipro-floxacin41,42, clarithromycin42, vancomycin37, penicillin44, diiodohydroxyquinoline44, strep-tomycin44, doxycycline61, sulfonamides25,67, and tetracycline.20,21 all biologic medications were combined into one category, as they were all tnf alpha blocking agents (infliximab3,14,22,31,41, adalimumab22,48,50, and golimumab68). drugs in the miscellaneous category were not included in the statistical analysis because all were used only once. this included intravenous immunoglobulin7, aurothiomalate7, acyclovir12, ketoconazole3, “antifungals40,” topical imiquimod, vitamin therapy70, diphenhydramine elixer70, and viscous lidocaine.70 statistical analysis each medication was compared across different subgroups to determine if any medications were more successful in patients with certain characteristics. these subgroups included: sex (male versus female), type of inflammatory bowel disease (ulcerative colitis (uc) versus crohn’s disease (cd)), presence of colitis, presence of eosinophilia, presence of elevated inflammatory markers (esr or crp), and subtype of pdv-psv (pdv only versus pdv only versus pdvpsv). this was done using 2x2 chi square tests to compare the number of times each treatment was successful versus unsuccessful within each subgroup. p-values were adjusted to account for running multiple tests using the holm method. skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 340 in this review, 128 related articles were identified using the search criteria discussed above (figure 1). after the initial abstract screening 38 articles were excluded. an additional 23 reports were excluded because they did not meet the inclusion criteria for this review. six additional articles were included from reference lists of pdv-psv review papers. for the final review, 74 reports were used, which included 72 case reports and 2 case series. this corresponded to 94 unique patients. no prospective or retrospective cohort trials were found for pdv-psv. with the addition of a patient from the authors’ institution, 95 total patients were used in this review an analysis. there was no evidence of duplicate cases. demographics of the study population are summarized in table 2. seventy-six patients (80%) had concomitant ibd. the median age was 35 (iqr=24) years old and 47 (49%) of the patients were female. the median number of treatments per patient was 2 (iqr=2), with a median follow-up time of up to 12 months (iqr=20). several treatments were found to be effective (with greater than 75% of patients having a complete response to the medication), including ocs, aza, 5-asa, ocni, and bio. t-cs/cni, colchicine, oral dapsone, and other antibiotics appeared to have lowest efficacy in treating the disease (table 3). ocs were the most commonly used treatment, used in 79 of 95 patients (83%). ocs also demonstrated strong efficacy with a complete response achieved in 80% (63/79) patients. osc was table 2. characteristics of the pdv-psv patients characteristics values total number of patients 95 female, n (%) 47 (49%) median age in years (iqr) 35 (24) ethnicity white/caucasian, n (%) 18 (19%) other, n (%) 8 (8%) unspecified, n (%) 69 (73%) associated with ibd/chronic colitis, n (%) 76 (80%) uc, n (%) 55 (72%) ibd presented before pdvpsv, n (%) 56 (74%) location of muco-cutaneous lesions psv only, n (%) 46 (48%) pdv-psv, n (%) 39 (41%) pdv only, n (%) 10 (11%) peripheral eosinophilia, n (%) 30 (32%) elevated inflammatory markers, n (%) 23 (24%) median follow up time in months (iqr) 12 (20) achieved complete response, n (%) 86 (91%) median number of treatments, n (iqr) 2 (2) abbreviations: crp, c-reactive protein; esr, erythrocyte sedimentation rate; ibd, inflammatory bowel disease; iqr, interquartile range; pdv, pyodermatitis vegetans; pdv-psv, pyodermatitis-pyostomatitis vegetans; psv, pyostomatitis vegetans; uc, ulcerative colitis. determined to be most successful when used as initial therapy, achieving cr-i in 49% (31/63) of patients achieving complete remission. topical therapies were used in nearly half of patients (45/95, 47%), but were often unsuccessful, resulting in complete resolution of lesions in only 49% (22/45) of cases. aza was used by 19 patients (22%) and found to be effective, resulting in cr in 12 (80%) patients. aza therapy was not found to be more successful in one subgroup of cr over another. results skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 341 table 3. total number of patients per response category by medication class number of within each response category (total patients = 95) number of patients within each complete response (cr) subgroup medication total patients (%) no response (%) partial response (%) complete response (%) cr-i (% of cr) cr-m (% of cr) cr-d (% of cr) ocs 79 (83%) 10 (13%) 6 (9%) 63 (80%) 31 (49%) 23 (23%) 9 (14%) t-cs/cni 45 (47%) 10 (22%) 12 (27%) 23 (51%) 6 (26%) 11 (48%) 6 (26%) dap 36 (38%) 10 (28%) 5 (14%) 21 (58%) 7 (33%) 13 (62%) 1 (5%) 5-asa 31 (33%) 5 (16%) 1 (3%) 25 (81%) 3 (12%) 21 (84%) 1 (4%) abx 29 (31%) 10 (34%) 4 (14%) 15 (52%) 3 (20%) 7 (47%) 5 (33%) aza 19 (20%) 5 (26%) 2 (11%) 12 (63%) 4 (33%) 5 (42%) 3 (25%) bio 9 (9%) 2 (22%) 0 (0%) 7 (78%) 1 (14%) 5 (71%) 1 (14%) col 6 (6%) 1 (17%) 1 (17%) 4 (67%) 3 (75%) 1 (25%) 0 (0%) ocni 4 (4%) 0 (0%) 0 (0%) 4 (100%) 2 (50%) 2 (50%) 0 0%) partial response was defined as incomplete resolution of lesions. complete response required evidence of good control of the disease after initiating or discontinuing the medication. abbreviations: 5-asa, sulfasalazine/sulphasalazine, aminosalicylates, mesalamine; abx, antibiotics; aza, azathioprine, mercaptopurine; bio, biologics; col, colchicine; cr, complete response; cr-d, complete response-discontinuation; cr-i, complete response – initial; cr-m, complete response – maintenance; dap, dapsone; ocni, oral calcineurin inhibitors; ocs, systemic corticosteroids; nr, no response; pr, partial response; t-cs/cni, topical corticosteroids or topical calcineurin inhibitor. 5-asa was used by 31 (33%) patients and found to be effective, with 25 (81%) patients achieving cr. bio were used by 9 (9%) patients and also found to effective, resulting in cr in 7 (78%) patients. 5-asa and bio were statistically most successful when used as maintenance therapies with 21/25 (84%) and 5/7 (71%) patients achieving a complete response when the therapies were used as maintenance, respectively. ocni were only used by four (4%) patients, but were still found effective, achieving complete response in 100% of patients. abx were used in 29 (31%) patients and found to be poorly effective, achieving complete response in only 15 (52%) individuals. dap was used by 36 (38%) patients and was also found to be ineffective, with 21 (58%) patients achieving any complete response. col was used by 6 (6%) patients and was found to be ineffective, despite 4/6 (67%) patients achieving complete response. a comparison of the medications’ success within subgroups was analyzed by chisquared test. no medications were found to be more successful when treating males versus females, patients with uc versus cd, patients with colitis versus without colitis, patients with versus without eosinophilia prior to initiating therapy, patients with versus without elevated inflammatory markers prior to initiating therapy, and patients with pdv versus psv versus pdv-psv. pyodermatitis-pyostomatitis (pdv-psv) is a rare mucocutaneous dermatosis characterized by pustular and vegetating lesions of the skin and oral mucosa. in the literature, 80% of cases of pdv-psv were associated with ibd, though gastrointestinal symptoms may not initially be present. therefore, the presence of pdv-psv should trigger further investigation for underlying ibd.16,35 the proposed mechanism and disease process of pdv-psv remains unknown. while the name “pyoderma” suggests skin infection, no consistent pathogenic bacteria, fungi, or viruses have discussion skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 342 been discovered.48 thus, pdv-psv is thought to result from an abnormal inflammatory response to unknown factors. due to the high proportion of pdv-psv cases associated with ibd, these factors are hypothesized to be antigens shared by bacteria in both the gut and the skin. multiple treatment options exist for pdvpsv, primarily targeting underlying ibd and the pathologic cutaneous inflammatory response. unfortunately, due to the rarity of pdv-psv, no controlled trials exist comparing different treatment modalities. healey et al published an initial treatment algorithm for only psv in 1994.29 consequently, drugs like biologics and calcineurin inhibitors, more commonly used now than 26 years ago, were not represented. the present review of treatment data from 95 cases provides updated evidence regarding the most effective therapies. multiple therapies are often required with widely varying levels of success. in the present review, many patients had success with oral corticosteroids when used initially, either followed by steroid-sparing maintenance therapy or when used intermittently for relapse control. improvement in skin and oral lesions generally correlated with treatment of underlying ibd, likely because of shared pathogenesis involving overactive inflammatory response.1,5,11,15,16,29,61,65,66 the results suggest that a patient, with or without ibd, may see benefit with a course of ocs as the initial intervention. in patients with active ibd, 5-asa may be helpful in managing both the ibd and mucocutaneous symptoms. 5-asa can also be attempted if ocs fail to result in remission for patients without associated ibd, as the data does not suggest an increased efficacy in ibd associated pdv-psv versus skin only disease. maintenance therapy can also be initiated if a patient is requiring frequent courses of ocs due to relapse of the disease. while topical steroids are currently considered first line treatment based on healey’s treatment algorithm, the data clearly demonstrates pdv-psv responds poorly to topical medications. oral dapsone and colchicine are also commonly used but demonstrate poor efficacy for the treatment of pdv-psv. antibiotics were found to be ineffective medications for the treatment of pdv-psv but should be considered if there is concern for superinfection. if the above medications fail, are poorly tolerated, or the provider or patient prefers, azathioprine or 6-mercaptopurine or an oral calcineurin inhibitor may be attempted for patients with or without associated ibd. in refractory cases, a tnf-alpha blocking biologic can be used. given their safety and significant effectiveness as maintenance therapies, biologics can also be considered earlier in the treatment course. however, data is limited by small sample size. this review has several limitations. first, there are no prospective studies regarding the treatment of pdv-psv due to the rarity of the disease, so this analysis is limited to case reports and case series. this lends to both publication and reporting bias. reports were likely not written and/or published if medications used to treat pdv-psv were ineffective, leading to a lack of negative data. additionally, studies may have selectively reported only positive outcomes, and there was no standardized way of reporting these outcomes. due to this lack of standardization of the magnitudes of the responses to the medications, response categories were created based on the specific phrases used in the primary literature. this made the vocabulary used in each article extremely important, as specific wording was skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 343 categorized as different levels of response. this use of categorization based on semantics is inherent in retrospective papers, as well as review papers. prospective data and controlled studies would be necessary to fully compare different regimens. furthermore, the reviewers grouped medications (such as topical medications and biologics) into classes for statistical analysis due to small sample sizes. this could mask the effects of individual agents. finally, follow-up time varied greatly (mean=28.3 months, range=1-252 months), thus making it difficult to determine long-term effects. some patients had no follow up or were seen as early as one-week post discontinuation of their medication(s). some papers did not record follow up results at all. because of this variation in follow-up reported, the maintenance of remission following discontinuation of a medication could not always be determined. when a patient is diagnosed with pdv-psv, it is important to evaluate for underlying ibd due to the high number of associated cases. no treatments proved to be more or less effective for ibd associated pdv-psv versus skin-only disease, but pdv-psv improvement tended to correlate with management of associated ibd if present. oral corticosteroids were the most commonly used and most effective medication at obtaining resolution of the mucocutaneous lesions of pyodermatitis-pyostomatitis vegetans. based on the literature review conducted, other effective treatments include azathioprine and 6-mercaptopurine, 5aminiosalicylic acid derivatives, oral calcineurin inhibitors, and tnf-alpha blocking biologics. it will be important to improve the evidence for the efficacy of these medications through rigorous prospective studies. acknowledgements: no external or internal funding. all authors declare that they have no conflict of interest. all contributors did necessary work to qualify for authorship, no other contributors. conflict of interest disclosures: none funding: none corresponding author: landon hobbs, bs department of dermatology university of virginia school of medicine 1215 lee street charlottesville, va 22903 phone: 434-924-5115 fax: 434-244-4504 email: 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th, kim s-c. pyodermatitis-pyostomatitis vegetans associated with crohn’s disease. ann dermatol. 2015 oct;27(5):624–5. 34. kitayama a, misago n, okawa t, iwakiri r, narisawa y. pyodermatitis-pyostomatitis vegetans after subtotal colectomy for ulcerative colitis: pyodermatitis-pyostomatitis vegetans. j dermatol. 2010 jul 22;37(8):714–7. 35. knapp n, khan z, albuquerque r, richards a, brown rm. pyostomatitis vegetans in ulcerative colitis; management with topical tacrolimus and systemic azathioprine in a 10-year-old boy (case report and review of the literature). j int oral health. 2015 aug 15;8(1):132–6. 36. ko h-c, jung d-s, jwa s-w, cho h-h, kim b-s, kwon k-s, et al. two cases of pyodermatitispyostomatitis vegetans. j dermatol. 2009 may;36(5):293–7. 37. konstantopoulou m, o’dwyer em, steele jc, field ea, lewis m a. o, macfarlane aw. pyodermatitis–pyostomatitis vegetans complicated by methicillin-resistant staphylococcus aureus infection. clin exp dermatol. 2005;30(6):666–8. 38. leibovitch i, ooi c, huilgol sc, reid c, james cl, selva d. pyodermatitis-pyostomatitis vegetans of the eyelids case report and review of the literature. ophthalmology. 2005 oct;112(10):1809–13. 39. li s, li z, feng s. low-dose sulfasalazine in a case of pyodermatitis-pyostomatitis vegetans. j am acad dermatol. 2018 oct 20; 40. lopez-jornet p, gomez-garcia f, camachoalonso f. pyostomatitis vegetans. clinical marker of ulcerative colitis. n y state dent j. 2012 mar;78(2):36–7. 41. lourenço sv, hussein tp, bologna sb, sipahi am, nico mms. oral manifestations of inflammatory bowel disease: a review based on the observation of six cases. j eur acad dermatol venereol jeadv. 2010 feb;24(2):204– 7. 42. maseda r, rodriquez ai, feito m, de lucas r. a case of pyoderma vegetans associated with crohn’s disease under adalimumab. j am acad dermatol. 2017 jun;76(6):ab8. 43. markiewicz m, suresh l, margarone j, aguirre a, brass c. pyostomatitis vegetans: a clinical marker of silent ulcerative colitis. j oral maxillofac surg. 2007 feb;65(2):346–8. 44. gold s. ulcerative colitis with pyodermite vegetante. proc r soc med. 1962 dec;55:1072– 3. 45. matias f de at, rosa dj de f, carvalho mtf de, castañon mcmn. pyodermatitispyostomatitis vegetans: case report and review of medical literature. an bras dermatol. 2011 aug;86(4 suppl 1):s137-140. 46. merkourea ss, tosios ki, merkoureas s, sklavounou-andrikopoulou a. pyostomatitis vegetans leading to crohn’s disease diagnosis. ann gastroenterol. 2013;26(2):187. 47. mesquita k de c, costa imc. case for diagnosis. an bras dermatol. 2012 dec;87(6):929–31. 48. mijandrusić-sincić b, licul v, gorup l, brncić n, glazar i, lucin k. pyostomatitis vegetans associated with inflammatory bowel disease-report of two cases. coll antropol. 2010 apr;34 suppl 2:279–82. 49. mizukami y, imanishi h, tateishi c, kaneshiro s, sowa-osako j, ohsawa m, et al. successful treatment of pyostomatitis vegetans with ulcerative colitis using dapsone without systemic steroids. 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publ int assoc oral pathol am acad oral pathol. 2012 sep;41(8):584–8. 56. niezgoda a, białecka a, marek-józefowicz l, skrzeczko-kwela e, czajkowski r. pyoderma gangrenosum with its subtype affecting oral mucosa pyostomatitis vegetans following skin melanoma surgical excision in a patient with ulcerative colitis: a case report. postepy dermatol alergol. 2018 apr;35(2):212–6. 57. nigen s, poulin y, rochette l, lévesque m-h, gagné e. pyodermatitis-pyostomatitis vegetans: skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 346 two cases and a review of the literature. j cutan med surg. 2003 jun;7(3):250–5. 58. o’hagan ah, irvine ad, allen ge, walsh m. pyodermatitis-pyostomatitis vegetans: evidence for an entirely mucocutaneous variant. br j dermatol. 1998 sep;139(3):552–3. 59. pazheri f, alkhouri n, radhakrishnan k. pyostomatitis vegetans as an oral manifestation of crohn’s disease in a pediatric patient. inflamm bowel dis. 2010 dec;16(12):2007. 60. 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[pyodermatitispyostomatitis vegetans with nasal involvement]. ann dermatol venereol. 2008 nov;135(11):753– 6. 61. ruiz-roca ja, berini-aytés l, gay-escoda c. pyostomatitis vegetans. report of two cases and review of the literature. oral surg oral med oral pathol oral radiol endod. 2005 apr;99(4):447– 54. 62. saghafi s, falaki f, bashardoost n. pyostomatitis vegetans: report of a rare case. pol j pathol off j pol soc pathol. 2011;62(2):125–8. 63. shah s, cotliar j. pyostomatitis vegetans. n engl j med. 2013 may 16;368(20):1918–1918. 64. soriano ml, martínez n, grilli r, fariña mc, martín l, requena l. pyodermatitis-pyostomatitis vegetans: report of a case and review of the literature. oral surg oral med oral pathol oral radiol endod. 1999 mar;87(3):322–6. 65. stingeni l, tramontana m, bassotti g, bianchi l, lisi p. pyodermatitis-pyostomatitis vegetans and antibullous pemphigoid antigen 180 autoantibodies: a casual association? br j dermatol. 2015 mar;172(3):811–3. 66. storwick gs, prihoda mb, fulton rj, wood ws. pyodermatitis-pyostomatitis vegetans: a specific marker for inflammatory bowel disease. j am acad dermatol. 1994 aug;31(2):336–41. 67. thornhill mh, zakrzewska jm, gilkes jjh. pyostomatitis vegetans: report of three cases and review of the literature. j oral pathol med. 1992 mar;21(3):128–33. 68. tursi a. concomitant hidradenitis suppurativa and pyostomatitis vegetans in silent ulcerative colitis successfully treated with golimumab. dig liver dis off j ital soc gastroenterol ital assoc study liver. 2016 dec;48(12):1511–2. 69. uzunçakmak t, akdeniz n, karadağ a, çobanoğlu b. pyodermatitis vegetans after total colectomy. indian dermatol online j. 2015;6(7):9. 70. vanhale hm, rogers rs, zone jj, greipp pr. pyostomatitis vegetans. a reactive mucosal marker for inflammatory disease of the gut. arch dermatol. 1985 jan;121(1):94–8. 71. wang h, qiao s, zhang x, liu c. a case of pyodermatitis-pyostomatitis vegetans. am j med sci. 2013 feb;345(2):168–71. 72. werchniak ae, storm ca, plunkett rw, beutner eh, dinulos jgh. treatment of pyostomatitis vegetans with topical tacrolimus. j am acad dermatol. 2005 apr;52(4):722–3. 73. wolz mm, camilleri mj, mcevoy mt, bruce aj. pemphigus vegetans variant of iga pemphigus, a variant of iga pemphigus and other autoimmune blistering disorders. am j dermatopathol. 2013 may;35(3):e53-56. 74. wray d. pyostomatitis vegetans. br dent j. 1984 nov 10;157(9):316–8. 75. yasuda m, amano h, nagai y, tamura a, ishikawa o, yamaguchi s. pyodermatitispyostomatitis vegetans associated with ulcerative colitis: successful treatment with total colectomy and topical tacrolimus. dermatology. 2008;217(2):146–8 powerpoint presentation angela moore1,2, lawrence j. green3, jodi l. johnson4, ayman grada5 1baylor university medical center, dallas, texas, usa, 2arlington research center, arlington, texas, usa, 3lawrence j. green, md, llc, george washington university school of medicine, washington, dc, usa 4departments of dermatology and pathology, feinberg school of medicine, northwestern university, usa, 5r&d and medical affairs, almirall (us), exton, pennsylvania, usa (grada@bu.edu) introduction methods efficacy safety conclusion efficacy and safety of narrow-spectrum oral sarecycline for moderate to severe acne vulgaris co-primary efficacy endpoints sc1401 sc1402 placebo n=485 sarecycline n=483 difference (95% ci) [p-value] placebo n=515 sarecycline n=519 difference (95% ci) [p-value] change from baseline in inflammatory lesion count at week 12, ls mean (se) -10.1 (0.6) -15.3 (0.6) -5.2 (-6.7, -3.6) [<0.0001] -10.7 (0.5) -15.1 (0.6) -4.4 (-5.8, -2.9) [<0.0001] iga success at week 12 10.5% 21.9% 11.05 (6.39, 15.72) [<0.0001] 15.3% 22.6% 7.30 (2.53, 12.07) [0.0038]  statistically significant reduction in mean absolute and percent inflammatory lesion count as early as week 3. iga success rates were 21.9% and 22.6% (sarecycline) versus 10.5% and 15.3% (placebo; p < .0001 and p = .0038)  statistically significant reduction in comedonal lesion count was observed at week 6 in sc1401, and at week 9 in sc1402 baseline week 12 iga score 4 1 inflammatory lesions 50 4 comedonal lesions 22 17 baseline week 12 iga score 4 1 inflammatory lesions 33 8 comedonal lesions 33 5 baseline week 12 iga score 3 0 inflammatory lesions 21 0 comedonal lesions 62 4 23 years-old female 19 years-old female 14 years-old male teaes common to tetracycline-class antibiotics sc1401 sc1402 placebo (n=483) sarecycline (n=481) placebo (n=513) sarecycline (n=513) nasopharyngitis 8 (1.7%) 15 (3.1%) 15 (2.9%) 13 (2.5%) headache 13 (2.7%) 13 (2.7%) 25 (4.9%) 15 (2.9%) gastrointestinal adverse events nausea 12 (2.5%) 22 (4.6%) 5 (1.0%) 10 (1.9%) vomiting 7 (1.4%) 10 (2.1%) 2 (0.4%) 3 (0.6%) diarrhea 8 (1.7%) 5 (1.0%) 6 (1.2%) 6 (1.2%) abdominal pain 6 (1.2%) 6 (1.2%) 1 (0.2%) 3 (0.6%) vestibular effects dizziness 7 (1.4%) 3 (0.6%) 4 (0.8%) 2 (0.4%) vertigo 0 0 0 0 tinnitus 0 0 0 0 phototoxic effects photosensitivity 0 0 0 1 (0.2%) sunburn 2 (0.4%) 3 (0.6%) 1 (0.2%) 4 (0.8%) vaginal yeast infections in females vulvovaginal candidiasis 0 3 (1.1%) 0 1 (0.3%) vulvovaginal mycotic infection 0 2 (0.7%) 0 3 (1.0%) moore a, green lj, bruce s, et al. once-daily oral sarecycline 1.5 mg/kg/day is effective for moderate to severe acne vulgaris: results from two identically designed, phase 3, randomized, double-blind clinical trials. journal of drugs in dermatology: jdd. 2018 sep;17(9):987-96. financial support provided by almirall, llc  sarecycline is a narrow-spectrum tetracycline-class antibiotic designed for the treatment of moderate-tosevere acne.  sarecycline’s narrow-spectrum anti-bacterial activity and lipophilicity may minimize side effects commonly associated with broad-spectrum tetracyclines, such as minocycline and doxycycline.  here, we report the results of 2 identically designed, phase 3 pivotal trials, sc1401 and sc1402, to evaluate the efficacy and safety of once-daily sarecycline (n=2002). males and females aged 9 to 45 years between 33 kg and 136 kg moderate to severe (iga ≥ 3) facial acne 20 – 50 inflammatory lesions ≤ 100 noninflammatory lesions ≤ 2 nodules subjects randomized 1:1 to sarecycline 1.5 mg/kg/day oral or placebo  two phase 3 multicentre, randomized, double-blind, placebo-controlled, parallel group studies  up to 35 day screening period to establish eligibility and baseline  12 week double-blind treatment with study visits at 3, 6, 9, and 12 weeks  co-primary efficacy endpoints:  absolute change in facial inflammatory lesion count at week 12  iga success – iga score of 0 (clear) or 1 (almost clear) and ≥ 2 point improvement from baseline  secondary efficacy endpoints included absolute and percent change from baseline in inflammatory and noninflammatory lesions at weeks 3, 6, 9 & 12. iga success for truncal acne was reported as well n=2002  the same iga scale was used for the chest and back assessments as for facial acne  back: significant improvements at week 12 in sc1401 (-32.9 vs -17.1%; p < 0.001) and sc1402 (-33.2 vs -25.7%; p < 0.05).  chest: significant improvements was seen at week 12in sc1401 (-29.5 vs -19.6%; p < 0.05) and sc1402 (-36.6 vs -21.6%; p < 0.001) facial acne truncal acne (back and chest)  the fda-approved narrow-spectrum antibiotic sarecycline was safe, well-tolerated, and effective for moderate to severe inflammatory acne vulgaris in patients 9 years old and older  significant reduction in inflammatory lesions as early as 3 weeks  significant improvement in truncal acne (chest and back) was reported  significant improvement on comedonal acne was reported as well  incidence of side effects commonly associated with tetracycline-class antibiotics was low (<5%) mailto:grada@bu.edu slide number 1 skin july 2018 volume 2 issue 4 copyright 2018 the national society for cutaneous medicine 248 brief article treatment of telangiectasia macularis eruptiva perstans with an intense pulsed light device william h. sipprell iii md a , harjot s. maan md b , sherrif f. ibrahim md phd a,c a department of dermatology, university of rochester medical center, rochester, ny b department of dermatology, sutter north advanced dermatology and laser center, yuba city, ca c department of oncology, university of rochester medical center, rochester, ny telangiectasia macularis eruptiva perstans (tmep) is a rare adult mastocytosis with prominent cutaneous manifestations. it was first described by parkes weber in the 1930s. 1 irregular red to brown telangiectatic macules, usually on the chest or limbs, are seen clinically. tmep can be a cause of significant morbidity with both cutaneous and extracutaneous symptoms. these include flushing, blisters, pruritus, ulcers, hypotension, dyspnea and gastrointestinal symptoms such as reflux and diarrhea. 2 overall, tmep is considered to have a good prognosis with the majority of cases lacking systemic involvement. 3,4 if skin biopsies are performed in patients with tmep, findings typically include dilated upper dermal capillaries and venules with an upper dermal inflammatory infiltrate, largely comprised of mast cells around neurovascular bundles. 5 various approaches have been used to treat the cutaneous manifestations of tmep including psoralen plus ultraviolet light a (puva), topical corticosteroids, electron beam radiation and the 585-nm flashlamppumped dye laser. 2,5-7 these approaches have shown variable success. there are no previous reports in the literature describing the treatment of tmep with an intense pulsed light (ipl) device. however, the characteristic cutaneous lesions, with dilated capillaries of the superficial venous plexus of abstract telangiectasia macularis eruptiva perstans (tmep) is a rare adult mastocytosis with prominent cutaneous manifestations including red to brown telangiectatic macules typically on the chest or limbs. tmep can be a cause of morbidity with associated cutaneous findings (e.g. flushing, pruritus, ulcers) and extracutaneous symptoms (e.g. dyspnea, reflux, diarrhea, hypotension). previous attempts to treat the cutaneous manifestations of tmep include puva, topical steroids, electron beam radiation, and 585-nm flashlamp-pumped dye laser. we report the first case of successful treatment of the cutaneous findings of tmep with intense pulsed light (ipl). the patient underwent 2 treatments with ipl spaced 3 months apart, and remained entirely clear at 14 months follow-up. case report skin july 2018 volume 2 issue 4 copyright 2018 the national society for cutaneous medicine 249 the dermis, lend themselves to such an approach. we present the case of a patient with tmep and the associated characteristic cutaneous manifestations who was successfully treated with ipl. the patient was a 53-year-old gentleman who presented with a 2-year history of diffuse red telangiectatic blanching macules on both arms, hands and shins. histology was consistent with tmep. over the previous 6 months he had two episodes of diffuse flushing and dizziness that lasted 1 hour. for these possible systemic components of disease, he was started on 10 mg of cetirizine nightly and advised to avoid histamine releasers like alcohol, anticholinergic medications, aspirin, nonsteroidal anti-inflammatory drugs, heat, friction and opioids. medical history revealed that the appearance of his arms and legs had a large impact on his life. incessant comments from others led him to become self-conscious, agoraphobic and he would not leave his home without full sleeve shirts and pants. on examination we found numerous, confluent, blanching arborizing small vessels coalescing into large patches over the dorsal hands, forearms, posterior upper arms (figures 1a-1e) and shins. in an effort to address his cutaneous findings, a trial with ipl was conducted. the patient’s bilateral arms underwent field treatment with an ipl device (cutera limelight, brisbane, california). using a handpiece size of 10 x 30 mm, an energy level of 14-18 j/s and a pulse width set to target vascular lesions (program a). the entire affected area was treated in a confluent and sequential manner with a single pass with 10% overlap. pretreatment with 150 mg of ranitidine and 180 mg of fexofenadine was used to mitigate any potential treatment-induced mast cell histamine release. after a single treatment there was a remarkable difference with only minimal remaining involvement. a second treatment to these areas was performed 3 months later with complete resolution. treatment associated adverse events included mild erythema and edema and mild discomfort that resolved within 48 hours. his arms remain entirely clear and without recurrence 14 months later (figure 2). figure 1. extensive telangiectasias noted pretreatment a: left arm b: right arm, c: left elbow, d: right posterior upper arm, e: left posterior upper arm. figure 2. post-treatment of bilateral arms showing complete resolution of telangiectasias 14 months after treatment. skin july 2018 volume 2 issue 4 copyright 2018 the national society for cutaneous medicine 250 the treatment of tmep is largely based on the degree of systemic involvement or clinical symptoms the patient may have. 4 aside from the possible systemic symptoms of tmep, its appearance can be unsightly and lead to significant social and emotional distress. patients may report agoraphobia, social anxiety and low self-esteem which can significantly affect their quality of life and functioning. our patient had an astonishing response with one treatment session with only minimal day of treatment mild discomfort and erythema but no long-term side effects. the therapy was tolerated well without textural change. he is without recurrence 14 months after treatment. he continues to take 10 mg of cetirizine daily for any possible systemic involvement and has been free of symptoms. there is no standard of care for the treatment of tmep. the experimental treatments described previously include puva therapy, total body electron beam therapy and 585-nm flashlamp-pumped dye laser treatment. phototherapy with puva or uvb therapy can be helpful in terms of both pruritus and cutaneous appearance but requires the patient to come in several times per week and the lesions have been noted to recur after several months. 6,7 moreover, the patient is exposed to uv radiation. a single case report of total body electron beam therapy demonstrates successful treatment of tmep. the patient was free of his intense pruritus and cutaneous findings for up to one year. however, the treatment is expensive and required 24 treatment sessions over 6 weeks. adverse effects of this therapy can include “mild erythema, xerosis, temporary scalp alopecia, nail stasis, desquamation, anhidrosis, minor parotiditis, nosebleeds, and blistering or edema of hands and feet, as well as gynecomastia in males.” 6 the 585-nm flashlamp-pumped dye laser has been reported to be effective for the treatment of tmep in two cases. in both cases, the lesions begin to recur after 1 year. moreover, one patient required general anesthesia and experienced immediate wheal and flare reaction to all treated lesions as well as swelling, pruritus and vesiculation of the lesions within 6-12 hours. 2 our patient experienced only minimal erythema and tolerated the treatment with topical anesthesia. previous histologic evaluation after treatment with a 585-nm flashlamp-pumped dye laser revealed fibrosis of the superficial vasculature, however, the number of mast cells were essentially unchanged. the authors suggested that the results were due to selective vascular fibrosis rather than destruction of mast cells. 2 this observation may imply that vascular laser therapy only treats the cutaneous appearance of the condition and does not address the underlying etiology and will not address any systemic symptoms that the patient may have. it is important that this be discussed with the patient as well as to inform them of the risk of eventual recurrence of their skin findings. in summary, ipl is an effective treatment option for the cutaneous manifestations of tmep. further studies are warranted to fully explore this option. discussion skin july 2018 volume 2 issue 4 copyright 2018 the national society for cutaneous medicine 251 conflict of interest disclosures: none funding: none corresponding author: william h. sipprell iii, md 400 red creek dr., suite 200 rochester, ny 14623 585-487-1440 (office) 585-334-5823 (fax) william.sipprell@gmail.com references: 1. nguyen nq. telangiectasia macularis eruptiva perstans. dermatol online j. 2004;10(3):1. 2. ellis dl. treatment of telangiectasia macularis eruptiva perstans with the 585-nm flashlamp-pumped dye laser. dermatol surg. 1996;22(1):33-37. 3. marrouche n, grattan c. tmep or not tmep: that is the question. j am acad dermatol. 2014;70(3):581-582. 4. costa dl, moura hh, rodrigues r et al. telangiectasia macularis eruptiva perstans: a rare form of adult mastocytosis. j clin aesthet dermatol. 2011;4(10):52-54. 5. sarkany rp, monk be, handfield-jones se. telangiectasia macularis eruptiva perstans: a case report and review of the literature. clin exp dermatol. 1998;23(1):38-39. 6. monahan tp, petropolis aa. treatment of telangiectasia macularis eruptiva perstans with total skin electron beam radiation. cutis. 2003;71(5):357-359. 7. sotiriou e, apalla z, ioannides d. telangiectasia macularis eruptive perstans successfully treated with puva therapy. photodermatol photoimmunol photomed. 2010;26(1):46-47. conclusions superior pasi 90 and iga 0/1 responses were observed with bimekizumab compared with ustekinumab at week 16. after one dose, faster onset of response was observed with bimekizumab compared with ustekinumab. clinical responses with bimekizumab were durable through week 52. bimekizumab was well-tolerated and the safety profile was consistent with previous studies.4,5,9,10 objectives to compare the efficacy and safety of bimekizumab with ustekinumab and placebo in patients with moderate to severe plaque psoriasis treated for one year. background bimekizumab is a monoclonal igg1 antibody that selectively inhibits il-17f in addition to il-17a. both of these interleukins are implicated in the immunopathogenesis of psoriasis.1–3 bimekizumab led to substantial clinical improvements in patients with moderate to severe plaque psoriasis (pso) in the phase 2 be able study, with no unexpected safety findings.4,5 methods adult patients with moderate to severe pso were enrolled in the pivotal phase 3 be vivid study (nct03370133), a randomized, double-blinded superiority study in which patients were treated with bimekizumab, ustekinumab, or placebo (figure 1). • the co-primary endpoints were superiority of bimekizumab versus placebo in 90% improvements from baseline in psoriasis area and severity index (pasi 90) and an investigator’s global assessment score of 0 or 1 (iga 0/1). • missing data were imputed with non-responder imputation (nri). • treatment emergent adverse events (teaes) were classified using meddra version 19.0. results patient population • baseline characteristics are shown in table 1. efficacy • at week 16, the proportions of patients receiving bimekizumab who achieved pasi 90 and iga 0/1 were significantly greater than for ustekinumab or placebo (figure 2). • response was rapid, with 76.9% of bimekizumab-treated patients achieving pasi 75 at week 4, compared to 15.3% for ustekinumab and 2.4% for placebo (p<0.001 vs ustekinumab and placebo). safety • overall, bimekizumab was well-tolerated and discontinuation due to teaes was low (table 2). • the vast majority of the oral candidiasis cases were localized, mild or moderate superficial infections, and did not lead to discontinuation (table 2). • all incidences of major adverse cardiac events (mace) occurred in patients with ≥2 pre-existing cardiovascular risk factors (table 2). • overall incidence of mace across the bimekizumab in pso clinical program (phase 2/phase 3/open-label extension to nov 1, 2019) was 0.66/100 patient-years and consistent with the background risk within the pso population and incidence for other anti-il biologics.6–8 k. reich,1 k.a. papp,2 a. blauvelt,3 r. langley,4 a. armstrong,5 r.b. warren,6 k. gordon,7 j.f. merola,8 c. madden,9 m. wang,9 v. vanvoorden,10 m. lebwohl11 figure 1 study design author affiliations: 1center for translational research in inflammatory skin diseases, institute for health services research in dermatology and nursing, university medical center hamburg-eppendorf and skinflammation® center, hamburg, germany; 2probity medical research and k papp clinical research, waterloo, on, canada; 3oregon medical research center, portland, or, usa; 4dalhousie university, halifax, ns, canada; 5keck school of medicine of usc, dermatology, los angeles, ca, usa; 6the dermatology centre, salford royal nhs foundation trust, manchester nihr biomedical research centre, university of manchester, manchester, uk; 7medical college of wisconsin, milwaukee, wi, usa; 8department of dermatology, brigham and women’s hospital and harvard medical school, boston, ma, usa; 9ucb pharma, raleigh, nc, usa; 10ucb pharma, brussels, belgium; 11icahn school of medicine, new york, ny, usa. presented at fall clinical dermatology conference 2020 | october 29–november 1 | las vegas, nv efficacy and safety of bimekizumab in patients with moderate to severe plaque psoriasis: results from be vivid, a 52-week phase 3, randomized, double-blinded, ustekinumaband placebo-controlled study references: 1durham l. curr rheumatol reports 2015;17:55; 2fujishima s. arch dermatol res 2010;302:499–505; 3johnston a. et al. j immunol 2013;190:2252–62; 4papp k. et al. jaad 2018;79:277–86, nct02905006; 5blauvelt a. et al. aad 2019 (op11180), nct03010527; 6fda briefing document, dermatologic and opthalmic drugs advisory committee, july 19 2016; 7kerkhof pc. et al. jaad 2016; 75:83–98; 8australian public report for ixekizumab, may 2017; 9glatt s. et al. br j clin pharm 2017;83(5):991–1001; 10glatt s. et al. ann rheum dis 2018;77:523–32. author contributions: substantial contributions to study conception/design, or acquisition/analysis/interpretation of data: kr, kap, ab, rl, aa, rbw, kg, jfm, cm, mw, vv, ml; drafting of the publication, or revising it critically for important intellectual content: kr, kap, ab, rl, aa, rbw, kg, jfm, cm, mw, vv, ml; final approval of the publication: kr, kap, ab, rl, aa, rbw, kg, jfm, cm, mw, vv, ml. author disclosures: kr: served as advisor and/or paid speaker for and/or participated in clinical trials sponsored by abbvie, affibody, almirall, amgen, avillion, biogen, boehringer ingelheim, bristol-myers squibb, celgene, centocor, covagen, dermira inc., eli lilly, forward pharma, fresenius medical care, galapagos, glaxosmithkline, janssen-cilag, kyowa kirin, leo pharma, medac, merck sharp & dohme, miltenyi biotec, novartis, ocean pharma, pfizer, regeneron, samsung bioepis, sanofi, sun pharma, takeda, ucb pharma, valeant, and xenoport. kap: honoraria and/or grants from abbvie, akros, amgen, arcutis, astellas, baxalta,boehringer ingelheim, bristol-myers squibb, canfite, celgene, coherus, dermira, dow pharma, eli lilly, forward pharma, galderma, genentech, gilead, glaxosmithkline, janssen, kyowa hakko kirin, leo pharma, medimmune, merck sharp & dohme, merck-serono, mitsubishi pharma, moberg pharma, novartis, pfizer, prcl research, regeneron, roche, sanofi aventis/genzyme, sun pharma, takeda, ucb pharma, and valeant/bausch health; consultant (no compensation) for astrazeneca and meiji seika pharma. ab: served as a scientific adviser and/or clinical study investigator for abbvie, aclaris, allergan, almirall, athenex, boehringer ingelheim, bristol-myers squibb, dermavant, dermira inc., eli lilly, forte, galderma, janssen, leo pharma, novartis, ortho, pfizer, rapt, regeneron, sandoz, sanofi genzyme, sun pharma, and ucb pharma, and as a paid speaker for abbvie. rl: honoraria from abbvie, amgen, centocor, pfizer, janssen pharmaceuticals, leo pharma, boehringer ingelheim, eli lilly, and valeant pharmaceuticals for serving as an advisory board member, principal investigator, and speaker. aa: research investigator and/or consultant for abbvie, bristol-myers-squibb, dermavant, dermira inc., eli lilly, janssen, leo pharma, khk, modernizing medicine, novartis, ortho dermatologics, regeneron, sanofi, sun pharma, and ucb pharma, rbw: research grants and/or consulting fees from abbvie, almirall, amgen, arena, avillion, bristol-myers squibb, boehringer ingelheim, celgene, eli lilly, janssen, leo pharma, novartis, pfizer, sanofi, and ucb pharma. kg: honoraria and/or research support from abbvie, almirall, amgen, boehringer ingelheim, bristol-myers squibb, celgene, dermira inc., eli lilly, janssen, novartis, pfizer, sun pharma, and ucb pharma. jfm: consultant and/or investigator for abbvie, aclaris, almirall, amgen, biogen, celgene, dermavant, eli lilly, glaxosmithkline, incyte, kiniksa, janssen, mallinckrodt, merck, momenta, novartis, pfizer, samumed, sanofi regeneron, science 37, sun pharma, and ucb pharma; speaker’s bureau for abbvie. cm, mw, vv: employees of ucb pharma. ml: employee of mount sinai which receives research funds from: abbvie, amgen, arcutis, astrazeneca, boehringer ingelheim, celgene, clinuvel, eli lilly, incyte, janssen research & development, llc, kadmon corp., llc, leo pharma, medimmune, novartis, ortho dermatologics, pfizer, sciderm, ucb pharma, inc., and vidac. consultant for allergan, almirall, arcutis, inc., avotres therapeutics, birchbiomed inc., boehringer ingelheim, bristol-myers squibb, cara therapeutics, castle biosciences, corrona, dermavant sciences, evelo, foundation for research and education in dermatology, inozyme pharma, leo pharma, meiji seika pharma, menlo, mitsubishi, neuroderm, pfizer, promius/dr. reddy’s laboratories, theravance, and verrica. acknowledgements: this study was funded by ucb pharma. we thank the patients and their caregivers in addition to the investigators and their teams who contributed to this study. the authors acknowledge susanne wiegratz, msc, ucb pharma, monheim am rhein, germany and eva cullen, phd, ucb pharma, brussels, belgium for publication coordination and critical review, daniel smith, ba (hons), costello medical, cambridge, uk, for medical writing and editorial assistance, and the costello medical design team for design support. all costs associated with development of this poster were funded by ucb pharma in accordance with the good publication practice (gpp3) guidelines. austekinumab dosing was based on weight: patients ≤100 kg at baseline received one ustekinumab 45 mg injection and one placebo injection, patients >100 kg at baseline received two ustekinumab 45 mg injections. synopsis patients were randomized 4:1:2 to receive bimekizumab every four weeks, placebo or ustekinumab methods to compare the efficacy and safety of bimekizumab with ustekinumab and placebo in patients with moderate to severe plaque psoriasis objective be vivid met both of its co-primary endpoints at week 16, with significantly higher pasi 90 and iga 0/1 responder rates vs placebo; superiority vs ustekinumab was also demonstrated results bimekizumab was superior to ustekinumab and placebo in pasi 90 and iga 0/1 at week 16, and was generally well tolerated with a safety profile consistent with phase 2 studies conclusion table 1 baseline characteristics figure 2 responder rates over 52 weeks (itt, nri) table 2 safety bsa: body surface area; dlqi: dermatology life quality index; iga 0/1: score of 0 (clear) or 1 (almost clear) with ≥2-category improvement relative to baseline in investigator’s global assessment, scored on a 5-point scale; il: interleukin; itt: intent-to-treat; lft: liver function test; mace: major adverse cardiac events; nec: not elsewhere classified; nri: non-responder imputation; pasi: psoriasis area severity index; pso: psoriasis; q4w: every 4 weeks; q12w: every 12 weeks; sd: standard deviation; sib: suicide-ideation behaviors; teaes: treatmentemergent adverse events; tnf: tumor necrosis factor. austekinumab (q12w) dosing was based on weight: patients ≤100 kg at baseline received one ustekinumab 45 mg injection and one placebo injection, patients >100 kg at baseline received two ustekinumab 45 mg injections; bincludes patients switching from placebo to bimekizumab 320 mg q4w at week 16; only events occurring after switching are included in this column; cone esophageal adenocarcinoma; done gastric cancer; eone basal cell carcinoma; fhypersensitivity reactions were predominantly cutaneous and subcutaneous, with no cases of anaphylaxis in any treatment group; gincidence of lft elevations among bimekizumab-treated patients was generally low and comparable to placebo and ustekinumab; hall fungal infections not classified as candida or tinea were classified as fungal infections nec; iin addition, all opportunistic infections were localized mucocutaneous fungal infections defined as opportunistic by convention; there were no systemic opportunistic infections or cases of active tuberculosis reported. austekinumab (q12w) dosing was based on weight: patients ≤100 kg at baseline received one ustekinumab 45 mg injection and one placebo injection, patients >100 kg at baseline received two ustekinumab 45 mg injections; *p<0.001 vs placebo; †p<0.001 vs ustekinumab; ‡nominal p<0.001 vs placebo; §nominal p<0.001 vs ustekinumab. p values for the comparison of treatment groups were based on the cochran–mantel–haenszel test from the general association; nominal p values for the general association were based on a stratified cochran–mantel–haenszel test where region and prior biologic exposure were used as stratification variables and were not controlled for multiplicity. at week 16, patients receiving placebo were switched to bimekizumab 320 mg q4w. a rapid response was observed, with over 75% of bimekizumabtreated patients achieving pasi 75 at week 4, after only one dose a) pasi 90 b) iga 0/1 c) pasi 100 initial period (weeks 0–16) initial and maintenance periods (weeks 0–52) placebo (n=83) n (%) bimekizumab 320 mg q4w (n=321) n (%) ustekinumaba (n=163) n (%) bimekizumab 320 mg q4wb (n=395) n (%) ustekinumaba (n=163) n (%) incidence of teaes any teae 39 (47.0) 181 (56.4) 83 (50.9) 323 (81.8) 130 (79.8) serious teaes 2 (2.4) 5 (1.6) 5 (3.1) 24 (6.1) 12 (7.4) discontinuation due to teaes 6 (7.2) 6 (1.9) 3 (1.8) 21 (5.3) 7 (4.3) drug-related teaes 8 (9.6) 79 (24.6) 19 (11.7) 147 (37.2) 33 (20.2) severe teaes 3 (3.6) 5 (1.6) 3 (1.8) 20 (5.1) 8 (4.9) deaths 1 (1.2) 1 (0.3) 1 (0.6) 2 (0.5) 1 (0.6) common teaes (>5% of patients) nasopharyngitis 7 (8.4) 30 (9.3) 14 (8.6) 86 (21.8) 36 (22.1) oral candidiasis 0 28 (8.7) 0 60 (15.2) 1 (0.6) upper respiratory tract infection 2 (2.4) 9 (2.8) 5 (3.1) 36 (9.1) 18 (11.0) urinary tract infection 5 (6.0) 6 (1.9) 2 (1.2) 12 (3.0) 7 (4.3) back pain 2 (2.4) 3 (0.9) 4 (2.5) 10 (2.5) 9 (5.5) headache 0 11 (3.4) 7 (4.3) 16 (4.1) 9 (5.5) hypertension 1 (1.2) 7 (2.2) 5 (3.1) 14 (3.5) 10 (6.1) safety topics of interest inflammatory bowel disease 0 1 (0.3) 0 1 (0.3) 0 adjudicated sib 0 0 0 1 (0.3) 1 (0.6) malignancies 1 (1.2)c 0 0 1 (0.3)d 1 (0.6)e neutropenia 0 2 (0.6) 0 4 (1.0) 1 (0.6) hypersensitivity reactionsf 0 16 (5.0) 10 (6.1) 47 (11.9) 15 (9.2) adjudicated mace 0 1 (0.3) 0 5 (1.3) 0 acute myocardial infarction 0 0 0 1 (0.3) 0 cardiac arrest 0 1 (0.3) 0 1 (0.3) 0 myocardial infarction 0 0 0 2 (0.5) 0 cerebral infarction 0 0 0 1 (0.3) 0 hepatic events 1 (1.2) 4 (1.2) 0 10 (2.5) 4 (2.5) liver function analysesg 1 (1.2) 4 (1.2) 0 8 (2.0) 4 (2.5) fungal infectionsh,i 0 45 (14.0) 1 (0.6) 92 (23.3) 4 (2.5) candida infections 0 33 (10.3) 0 72 (18.2) 1 (0.6) tinea infections 0 5 (1.6) 0 11 (2.8) 1 (0.6) pbo/bimekizumab 320 mg q4w (n=83) bimekizumab 320 mg q4w (n=321) ustekinumaba (n=163) age (years), mean ± sd 49.7 ± 13.6 45.2 ± 14.0 46.0 ± 13.6 male, n (%) 60 (72.3) 229 (71.3) 117 (71.8) caucasian, n (%) 63 (75.9) 237 (73.8) 120 (73.6) weight (kg), mean ± sd 89.1 ± 26.4 88.7 ± 23.1 87.2 ± 21.1 duration of pso (years), mean ± sd 19.7 ± 13.8 16.0 ± 11.6 17.8 ± 11.6 pasi, mean ± sd 20.1 ± 6.8 22.0 ± 8.6 21.3 ± 8.3 bsa (%), mean ± sd 27.0 ± 16.3 29.0 ± 17.1 27.3 ± 16.7 iga, n (%)b 3: moderate 54 (65.1) 201 (62.6) 96 (58.9) 4: severe 28 (33.7) 119 (37.1) 66 (40.5) dlqi total, mean ± sd 10.0 ± 6.8 9.9 ± 6.3 11.0 ± 6.9 any prior systemic therapy, n (%) 64 (77.1) 267 (83.2) 132 (81.0) prior biologic therapy, n (%) 33 (39.8) 125 (38.9) 63 (38.7) anti-tnf 16 (19.3) 51 (15.9) 24 (14.7) anti-il-17 18 (21.7) 76 (23.7) 38 (23.3) anti-il-23 5 (6.0) 16 (5.0) 6 (3.7) austekinumab (q12w) dosing was based on weight: patients ≤100 kg at baseline received one ustekinumab 45 mg injection and one placebo injection, patients >100 kg at baseline received two ustekinumab 45 mg injections; bin each treatment group, one patient with mild iga score was mistakenly enrolled. previously presented at aad 2020 n=321 n=163 n=83 week 16baseline week 52 2–5 weeks bimekizumab 320 mg q4w bimekizumab 320 mg q4w placebo ustekinumab 45/90 mg q12wa 20 weeks after last dose: safety follow-up open-label extension study (be bright) 4:1:2 randomization n=567 co-primary endpoints pasi 90 and iga 0/1 at week 16 screening initial treatment period active comparator period maintenance period 25 75 50 0 100 p ro p o rt io n o f p a ti e n ts a c h ie vi n g p a s i 9 0 ( % ) 012 4 128 16 20 24 28 32 36 4440 48 52 4.8% 49.7% 55.8% 81.6%† 85.0%*† 2.4% 3.1% 43.6%‡§ p<0.001p<0.001 25 75 50 0 100 p ro p o rt io n o f p a ti e n ts a c h ie vi n g i g a 0 /1 ( % ) 012 4 128 16 20 24 28 32 36 4440 48 52 77.9%† 60.7% 4.8%2.4% 12.9% 53.4% 49.8%‡§ 84.1%*† p<0.001p<0.001 25 75 50 0 100 p ro p o rt io n o f p a ti e n ts a c h ie vi n g p a s i 10 0 ( % ) 012 4 128 16 20 24 28 32 36 4440 48 52 38.0% 64.2%§ 58.6%*§ 20.9% 0%1.2% 15.0% p<0.001 p<0.001 ustekinumaba (n=163) bimekizumab 320 mg q4w (n=321)placebo (n=83) 2.4% week week week week 16 iga 0/1 proportion of patients achieving iga 0/1 (%) week 16 pasi 90 proportion of patients achieving pasi 90 (%) ustekinumab (n=163) 4.8% 4.8% bimekizumab 320 mg q4w (n=321) 84.1% placebo (n=83) ustekinumab (n=163) bimekizumab 320 mg q4w (n=321) placebo (n=83) 85.0% 49.7% 53.4% p<0.001 p<0.001 p<0.001 p<0.001 skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 947 skinmages actinomycetoma following traumatic inoculation of nocardia brasiliensis mckenzie a. dirr, md1, mary dick, md2, alan s. boyd, md2,3, philip b. milam, md2 1 medical university of south carolina, college of medicine, charleton, sc 2 vanderbilt university medical center, department of dermatology, nashville, tn 3 vanderbilt university medical center, department of pathology, nashville, tn a 32-year-old male without significant past medical history presented with acute-onchronic, mildly tender, enlarging, draining nodules and sinus tracts on the right lower extremity. the lesions had been present for 2 years following a penetrating injury at a construction site in central mexico. he sought local hospital attention after the injury and was treated with penicillin. he had temporary improvement in nodule formation and subsequent healing with atrophic scars; however, after the completion of antibiotics, the nodules redeveloped and progressed distally down the leg. at presentation, he was afebrile, and without signs of systemic infection. an mri of the right leg revealed widespread superficial soft tissue nodules, fascial edema, and no evidence of bone involvement. a chest, abdomen, and pelvis ct was unremarkable. examination of the right leg revealed multiple pink atrophic scars with hyperpigmented borders and erythematous nodules draining serous fluid (figure 1). infectious workup skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 948 was negative for hiv, syphilis, cryptococcosis, blastomycosis, and coccidiomycosis. fungal and acid-fast bacilli (afb) blood cultures were negative. a wedge excision down to fascia was obtained from an active nodule. histopathology demonstrated suppurative dermal inflammation with filamentous organisms and surrounding eosinophilic fringe consistent with nocardiosis or actinomycotic organisms (figure 2). tissue culture was positive for nocardia brasiliensis approximately 20 days later, confirming diagnosis of actinomycetoma. mycetomas ensue from implantation of a pathogen into skin resulting in edema, nodules, abscesses, fistulas, sinuses, and purulent drainage with variably colored granules.1,2,3 there are several subtypes of mycetomas, including eumycotic (fungal pathogens), botryomycosis (bacterial pathogens), and actinomycotic (filamentous branching organisms, including nocardia species).1 most mycetomas occur following trauma with exposure to contaminated soil.1 actinomycetomas can be caused by various species of aerobic filamentous organisms, including nocardia brasiliensis, a grampositive, filamentous, aerobe found in soil.1,2,3 chronic infections may result from this microbe’s capacity to adapt and survive the host’s immune response. differential expression of non-coding rna may play a role in this process.2 diagnosis can be made by evaluating tissue samples or wound cultures with pathogen visualization.3 actinomycetomas contain granules up to 1μm in size, and nocardia species appear as white or yellow/orange chalky colonies on culture that typically grow after one week.3 treatment consists of prolonged antibiotic treatment with trimethoprim-sulfamethoxazole (tmp-smx) or dapsone combined with an aminoglycoside, either amikacin or streptomycin. 1 recent studies have found success with linezolid and rifampin.4 actinomycetomas commonly affect central and south american males around 20-50 years old. 1 while this diagnosis is uncommon in the united states, it is important to elucidate the history of this condition to facilitate quick identification and treatment in regions where the disease is not endemic. conflict of interest disclosures: none funding: none corresponding author: mckenzie a. dirr, md medical university of south carolina 96 jonathan lucas street suite 601, msc 617 charleston, sc 29425 phone: 843-792-2081 email: dirr@musc.edu references: 1. bolognia j, schaffer jv, cerroni l. dermatology. fourth edition. bolognia j, schaffer jv, cerroni l, editors. fungal diseases, elewski b, hughey l, hunt km, hay rj. philadelphia, pa: elsevier; 2018. 1329-1363 2. cruz-rabadán js, miranda-ríos j, espínocampo g, méndez-tovar lj, maya-pineda hr, hernández-hernández f. non-coding rnas are differentially expressed by nocardia brasiliensis in vitro and in experimental actinomycetoma. the open microbiology journal. 2017;11(1):112– 25. 3. welsh o, vera-cabrera l, welsh e, salinas mc. actinomycetoma and advances in its treatment. clinics in dermatology. 2012;30(4):372–81. 4. sardana k, chugh s. newer therapeutic modalities for actinomycetoma by nocardia species. international journal of dermatology. 2018;57(9):e64–e65. fc20 poster kirsch cl108 = brandon kirsch, md1, janet dubois, md2, martin n. zaiac3, sanjeev ahuja, md, mba, facp4, deepak chadha, ms, mba, rac5 1kirsch dermatology, naples, fl, 2dermresearch inc., austin, tx, 3sweet hope research specialty, hialeah, fl , 4former cmo, brickell biotech, inc., boulder, co, 5brickell biotech, inc., boulder, co a multi-center, open-label extension study to assess the long-term safety, tolerability and pharmacokinetics, and explore the efficacy of sofpironium bromide gel, 15% applied topically to children and adolescents, 9 to 16 years of age, with primary axillary hyperhidrosis (bbi-4000-cl-108) hyperhidrosis affects approximately 15 million americans. sofpironium bromide is a retrometabolically designed analog of glycopyrrolate (anticholinergic) in development for the topical treatment of primary axillary hyperhidrosis. retro-metabolically designed drugs are intended to be rapidly metabolized in the bloodstream, potentially allowing for optimal therapeutic effect at the site of application with minimal systemic side effects. approximately 2.1% of individuals <18 years of age have primary hyperhidrosis with ~65% having axillary hyperhidrosis.1 the long-term safety, tolerability and efficacy of topical treatments for axillary hyperhidrosis have rarely been studied in the pediatric population. the mean age (sd) of the subjects was 13.3 (2.29) years. sixteen subjects completed 24-weeks of treatment. seven subjects had treatment emergent adverse events (teaes). four subjects had teaes that were considered related to study drug, which included expected systemic anticholinergic effects (blurred vision, dry mouth, dry eyes, mydriasis) and local site reactions (pain, pruritus, rash, erythema). two subjects discontinued the study due to adverse events, which included dry eye, dry mouth, pruritus and rash. the majority of subjects did not have any local signs or symptoms and none were severe. pharmacokinetic analysis did not show any evidence of sofpironium or bbi-4010 (major metabolite) accumulation, with most subjects having plasma concentrations that were not quantifiable. for the validated patient-reported outcome measure hyperhidrosis disease severity measure-axillary (hdsm-ax), the mean (sd) change from baseline (from study bbi-4000-cl-105) to week 24 of this study was -1.91 (1.038). a change of -1.00 represents clinically meaningful improvement. in this 24-week study in the pediatric population, sofpironium bromide gel, 15% appeared safe and generally well tolerated. the majority of subjects did not report any teaes, and there were no severe or serious aes. there was no evidence of drug accumulation. there was clinically meaningful improvement in axillary hyperhidrosis. brickell biotech, inc. supported the study and preparation of this abstract. funding statement conclusion background methods academic poster presented at the 2020 fall clinical dermatology conference | las vegas, nv | october 29 november 1, 2020 objective evaluate the long-term safety, tolerability and pharmacokinetics of topically applied sofpironium bromide gel, 15% for the treatment of axillary hyperhidrosis in pediatric subjects, as well as to explore efficacy. figure 1: sofpironium and bbi-4010 plasma concentration levels table 1: incidence & severity of teaes (n=21) results twenty-one subjects with primary axillary hyperhidrosis of ≥6 months duration ranging in age from 9 to 16 years, who had participated in and completed a previous 1-week safety and pharmacokinetic (pk) study (bbi-4000-cl-105), were enrolled and treated with sofpironium bromide gel, 15% applied to the axillae for 24 weeks. 1doolittle j, walker p, mills t, thurston j. hyperhidrosis; an update on prevalence and severity in the united states. arch dermatol res. 2016; 308:743-749. references 0 0. 1 0. 2 0. 3 wee k 0 wee k 4 wee k 24c o n ce n tr a ti o n ( n g /m l) nominal timepoint so fp iro niu m b bi -40 10 pk study (bbi-4000-cl-105) day 8 (± 1 day)/visit 4 day 28 (±3)/ visit 2 week 26/ end of study day 1/ visit 1 1 pump (~0.67ml) applied to each axilla, once daily, before bedtime day 56 (±5)/ visit 3 day 84 (±5)/ visit 4 day 112 (±5)/ visit 5 day 140 (±5)/ visit 6 day 168 (±5)/ visit 7 day 182 (±5)/ visit 8 week 4 week 8 week 12 week 16 week 20 week 24/ end of treatment or early termination week 0 screening/enrollment pk sample ≥12 hours after last dose pk sample ≥12 hours after last dose subjects with teaes 7 (33.3%) number of teaes 21 subjects with treatment-related aes 4 (19.0%) subjects with saes 0 subject discontinuations due to teae 2 (9.5%) teae by severity (all teaes) mild 5 (23.8%) [8] moderate 5 (23.8%) [13] teae by severity (relationship – possibly, probably or definitely related) mild 3 (14.3%) [4] moderate 4 (19.0%) [11] table 2: frequency of anticholinergic teaes (≥5%) (n=21) dry eye 1 (4.8%) [1] dry mouth 1 (4.8%) [1] mydriasis 1 (4.8%) [1] vision blurred 1 (4.8%) [1] note: a teae is defined as any ae occurring on or after first dose. the first number corresponds to the count of unique subjects and percentage, while the second number in [n] is the count of raw events. subjects are counted only once at the strongest relationship to the study medication. 0 1 2 3 4 b aselin e wee k 24 h d s m -a x s co re study timepoint the hyperhidrosis disease severity measure-axillary© (hdsm-ax) is a validated 11-item measure of axillary hyperhidrosis severity and frequency with a 5-point scale for each item. a change of -1.00 from the mean baseline score has been defined to represent clinically meaningful improvement. figure 2: hyperhidrosis disease severity measure-axillary (hdsm-ax) scores figure 3: patient global assessment of severity (pgi-s) 0 2 4 6 8 10 ve ry s e ve re s e ve re m oder ate m i ld non en u m b e r o f s u b je ct s severity b aselin e wee k 24 0 2 4 6 8 10 v e ry mu ch w o r se m od er ate ly w o r se a lit tle w or se a lit tle be tt e r m od er ate ly b e tt e r v e ry mu ch b et te rn u m b e r o f s u b je ct s change wee k 12 wee k 24 pgi-c: the response that best describes the overall change in underarm sweating since the subject started taking the study medication. patient global impression of severity (pgi-s): the response that best describes the severity of underarm sweating over the past week. figure 4: change in global assessment of severity (pgi-c) any present minimal mild moderate severe subjects with any local symptoms by worst severity 10 (47.6%) 4 (19.0%) 1 (4.8%) 5 (23.8%) 0 burning 4 (19.0%) 1 (4.8%) 1 (4.8%) 2 (9.5%) 0 stinging 3 (14.3%) 1 (4.8%) 1 (4.8%) 1 (4.8%) 0 itching 7 (33.3%) 2 (9.5%) 2 (9.5%) 3 (14.3%) 0 scaling 1 (4.8%) 1 (4.8%) 0 0 0 erythema 9 (42.9%) 4 (19.0%) 2 (9.5%) 3 (14.3%) 0 note: the severity shown is the greatest severity reported for a particular assessment (burning/stinging/itching/scaling/erythema). maximum severity assessed for either axilla is reported. table 3: local site reactions (n=21) skin september 2017 volume 1 issue 2 copyright 2017 the national society for cutaneous medicine 64 in-depth reviews antibiotic resistance considerations of importance to clinical dermatologists james q. del rosso, do a a adjunct clinical professor (dermatology), touro university nevada, henderson, nevada; research director, jdr dermatology research, las vegas, nevada; dermatology and cutaneous surgery, thomas dermatology, las vegas, nevada. the topic of antibiotic resistance has gained progressive attention globally in the lay press, in the medical literature, and among several organizations who are actively promoting antibiotic stewardship in the united states (us) and many other countries. 1-10 in fact, many countries, such as in europe, have preceded the us in strongly promoting initiatives to limit antibiotic prescribing over the past few decades due to concerns related to the consequences of widespread antibiotic resistance and the slow development of new antibiotics. 1-3,8,9 in the us and within the specialty of dermatology, the scientific panel on antibiotic use in dermatology (spaud), a project administered by the american acne & rosacea society (aars), has been evaluating antibiotic use within the dermatology specialty since 2005 and has provided educational initiatives and publications related to the subject of bacterial resistance to antibiotics and optimal antibiotic prescribing. 2,3,11-15 several leading dermatologists with strong clinical and academic interest in abstract antibiotic resistance is a major health concern worldwide as the list of bacterial pathogens that are insensitive to available antibiotics continues to grow in both hospitals and outpatient communities. the slow development of newer antibiotics adds to the formidable challenge that clinicians face with treatment of infections caused by antibiotic-resistant bacteria. this article discusses important caveats related to antibiotic use in dermatology. these include understanding that both topical and oral antibiotics contribute to the emergence and spread of resistant bacteria, that antibiotic monotherapy is to be avoided for treatment of acne vulgaris, that effective treatment of rosacea does not require the use of an antibiotic, that antibiotic therapy in the management of atopic dermatitis is best limited to treatment of an active clinical infection, and that routine post-operative use of a topical antibiotic is not suggested after most office-based dermatologic procedures. by following principles of antibiotic stewardship, dermatologists are major players in the battle against antibiotic resistance. introduction skin september 2017 volume 1 issue 2 copyright 2017 the national society for cutaneous medicine 65 this subject area have contributed to the activities of spaud and its publications. 15 this article highlights five important top line observations that may assist dermatologists in optimal antibiotic prescribing, avoiding antibiotic use where it is not needed, and reducing the emergence of antibiotic-resistant bacteria. (1) topical antibiotics contribute to antibiotic resistance at sites of application and at sites remote from where they are applied topical antibiotic agents, especially clindamycin and erythromycin, are commonly used for treatment of acne vulgaris (av). it has been recommended that they be applied concomitantly with benzoyl peroxide (bp) to reduce emergence of resistant strains of propionibacterium acnes. 16-18 however, this may not occur reliably, either because the prescriber does not combine both agents, or the patient does not acquire or utilize both agents together. it has been demonstrated that topical antibiotic therapy (ie erythromycin) induces resistant strains of p acnes and staphylococci on the face where it was applied, but also resistant bacteria on the back and anterior nares where it was not applied. 19-21 it has also been shown that clindamycin-resistant group b streptococcus strains are not uncommon, including in pregnant women where untoward sequelae may occur, and may be associated with multi-drug resistance. 22,23 topical use of clindamycin, especially monotherapy, may contribute to the increase in resistant bacterial pathogens, including streptococci, staphylococci, and p acnes. 13,24 (2) antibiotic monotherapy is not recommended in the treatment of acne vulgaris although the concept of avoiding antibiotic monotherapy for av is practically intuitive among almost all dermatologists, it is important that it be stressed, especially in an era when patients do not always get access to all the medications that are prescribed. factors that contribute to this include the amount of prescription copays, insurance coverage, attempts by pharmacies to change what is prescribed, patients running out of some medications and not making contact to arrange refills, and patients electing not to use some of the medications that were prescribed. therefore, it is important to verify at each visit what patients are actually using day to day to treat their av to assure that antibiotic monotherapy is avoided. the rationale for avoiding monotherapy with oral and/or topical antibiotics is reduction in emergence of antibiotic-resistant bacteria, both p acnes, and other organisms that comprise the commensal and transient flora. 1,3,11-13 to add, normal flora bacteria such as staphylococcus epidermidis are capable of transferring resistance genes to potentially pathogenic bacteria such as s aureus. 21-23,25 this compounds the ecologic mischief related to antibiotic use, whereby emergence of resistant bacteria in a given individual can affect larger communities as individuals pass bacteria to others they are in close contact with, and the bacteria may pass resistance genes to other bacteria that are of different genus and/or species. importantly, topical antibiotics affect the microbiota of the skin and regional mucosa (ie anterior nares); oral antibiotics have a more widespread impact, affecting the microbiota of the skin/nares, oropharyngeal region, gastrointestinal tract, and genitourinary tract. 3,13 the clinical efficacy skin september 2017 volume 1 issue 2 copyright 2017 the national society for cutaneous medicine 66 of antibiotic therapy for av can be adversely impacted by the emergence of an adequate magnitude of antibiotic-resistant p acnes strains. 3,11,12,24,26 in addition, reducing antibiotic use in a given community can reduce the prevalence of bacteria resistant to that antibiotic over time, supporting the importance of judicious prescribing of antibiotic therapy. 27-29 (3) management of rosacea does not require an antibiotic effect to achieve therapeutic benefit available evidence supports that the pathophysiology of rosacea, including cases presenting as diffuse centrofacial erythema with or without papulopustular lesions, involves both cellular and neurovascular inflammatory pathways, and is not related to the presence/proliferation of a specific bacterium. 30-34 as a result, many of the studies of therapies used to treat rosacea (eg tetracyclines, azelaic acid, ivermectin) especially with presence of papulopustular lesions, appear to affect inflammatory pathways/modes of action unrelated to an underlying bacterial trigger that appear to be operative in rosacea pathophysiology (eg inhibition of matrix metalloproteinases, downregulation of cathelicidin pathway, reduction in number of demodex mites). 35-43 the large body of evidence supporting an inflammatory pathogenesis of rosacea that is not triggered by a bacterial etiology has led globally to rosacea management recommendations supporting that avoidance of an antibiotic effect whenever possible is favorable in order to reduce the emergence of antibiotic-resistant bacteria. 44-47 in their rosacea medical management guidelines, the american acne & rosacea society stated the following: “the lack of data supporting a bacterial component definitively related to the pathogenesis of rosacea suggests overall that medical therapies which are anti-inflammatory in nature are best considered for initial treatment of rosacea, especially the inflammatory (papulopustular) subtype, with oral antibiotic agents used in cases that are poorly responsive to a reasonable trial of topical therapy and/or oral anti-inflammatory therapy”. 44 to achieve this, available topical agents with demonstrated anti-inflammatory effects, efficacy, and safety in rosacea would include azelaic acid and ivermectin. 41,42,44-49 sub-antibiotic dose doxycycline (such as the modified-release 40 mg capsule once daily or 20 mg immediate-release tablet twice daily) provides anti-inflammatory effects with efficacy and favorable safety for rosacea, without inducing antibiotic selection pressure. 40,44-47,50 (4) antibiotic use in atopic dermatitis is best limited to treatment of skin infection with avoidance of chronic suprressive oral or topic antibiotic therapy atopic skin is commonly colonized with s aureus, with presence on eczematous skin, uninvolved skin, and within anterior nares in 85%, 60%, and 60% of cases, respectively. 51-54 this skin colonization information, coupled with the suggestion that certain strains of s aureus may induce and/or prolong exacerbations of atopic dermatitis (ad) via production of specific toxins and other exoproducts, has led to a greater frequency of antibiotic use to manage and suppress ad. 52,54 when a cutaneous infection is diagnosed clinically, antibiotic therapy is therapeutically beneficial in ad. however, chronic topical or oral antibiotic therapy is not recommended as a treatment to manage or suppress ad in the absence of a true skin infection, and it skin september 2017 volume 1 issue 2 copyright 2017 the national society for cutaneous medicine 67 serves only to promote antibiotic resistance. 3,14,52 in fact, in the management of ad, topical corticosteroid therapy and topical epidermal barrier repair can reduce the density of s aureus that is present on eczematous dermatitis by decreasing skin inflammation and by mitigating both the permeability barrier and antimicrobial barrier dysfunctions associated with atopic skin and ad. 14,52,56-58 to summarize, it is recommended that antibiotic therapy be limited in the management of ad to treatment of actual clinical skin infection; chronic suppressive therapy is not suggested as this approach has not been shown to be effective and promotes the development of antibiotic-resistant bacterial strains such as s aureus. (5) use of a topical antibiotic agent is not suggested for routine use after superficial cutaneous surgeries performed in the outpatient office setting a meta-analysis based on data pooled from four studies failed to demonstrate a statistically significant difference between application of topical antibiotics versus topical petrolatum/paraffin in preventing post-surgical infections after dermatologic procedures. 58 this is especially relevant clinically in the office-based dermatology setting where many cutaneous surgeries are superficial (eg most biopsies, curettage, saucerization, cryotherapy) and involve clean or clean-contaminated surgical wounds. 14,52,58 another study (n=1207 wounds) compared post-procedure application of white petrolatum ointment or bacitracin ointment used daily over a duration of 7 to 10 days (n=1207 wounds); contact dermatitis was noted in 0.9% of patients who applied bacitracin daily as compared to none of the patients applying white petrolatum daily. 59 available evidence suggests that routine postsurgical use of a topical antibiotic is not recommended overall after office-based dermatologic procedures, especially those that are not at high risk of infection; this includes clean and cleancontaminated wounds, after procedures in patients that are immunocompetent and not at high risk of infection, after surgeries performed in regions above the knee, and after surgeries not involving the groin, ears, or mucosal region of the nose or mouth. 14,52,60,61 in selected cases where the risk of post-operative infection is deemed to be high and avoidance of infection is a major priority due to patient-related risk factors, it is believed to be a better choice to utilize oral antibiotic prophylaxis as topical therapy alone is not as likely to provide adequate prevention of infection in such cases. 14,52 antibiotic resistance continues to be a major health concern worldwide. the list of pathogens that are less sensitive to available antibiotics both within hospitals/health care facilities, and within urban and rural communities continues to grow. coupled with the slow development of new and novel antibiotics and other alternative antibiotic approaches, the increase in antibiotic-resistant bacteria present a formidable challenge for clinicians. each clinician can assist in the fight against resistance by using antibiotics only when they feel they are clearly needed to treat a given patient, and in regimens that are optimal for treatment of the disease state being targeted. this article emphasizes the importance of recognizing that both topical and oral antibiotics contribute to the emergence and spread of resistant bacteria, that antibiotic monotherapy is to be avoided for treatment of av, that effective treatment of rosacea does not necessitate the use of summary skin september 2017 volume 1 issue 2 copyright 2017 the national society for cutaneous medicine 68 table 1: clinical caveats related to antibiotic use in dermatology 3,11-14,16,17,19,20,26,44-56,58-60 tables topical antibiotics used to treat acne vulgaris can induce the emergence of antibiotic-resistant bacteria.  facial application of topical erythromycin was associated with an increase in resistant staphylococci and p acnes on the face and on the back; resistant staphylococci were also noted in the anterior nares. antibiotic monotherapy is not recommended for the treatment of acne vulgaris.  increased emergence of antibiotic-resistant bacteria such as p acnes occurs especially in the absence of concomitant benzoyl peroxide use.  decreased activity against p acnes has been correlated with decreased therapeutic effect in acne vulgaris. evidence to date supports that the pathophysiology of rosacea does not involve pathways induced by a bacterium. an antibiotic effect is not needed for effective treatment of rosacea, nor does it appear to contribute to therapeutic activity in this disease.  anti-inflammatory therapies that appear to modulate inflammatory pathways operative in rosacea, especially when papulopustular lesions are present, include some topical agents and sub-antibiotic dose doxycycline therapy. use of topical or oral antibiotic therapy in atopic dermatitis is suggested for treatment of an active skin infection.  chronic antibiotic use is not suggested for management or suppression of atopic dermatitis as this approach is not effective and contributes to the emergence of antibiotic-resistant bacteria. available evidence supports that routine use of a topical antibiotic after office-based elective dermatologic procedures is not recommended, especially in those cases that are not at high risk of infection such as with clean and clean-contaminated wounds, and in immunocompetent patients.  overall, the potential for skin infection after superficial dermatologic procedures is low, and is not reduced by application of a topical antibiotic ointment as compared to white petrolatum ointment.  use of a topical antibiotic (such as those containing bacitracin and/or neomycin) is associated with a definite risk of allergic contact dermatitis; patients may often confuse these reactions with post-operative infection. skin september 2017 volume 1 issue 2 copyright 2017 the national society for cutaneous medicine 69 an antibiotic, that antibiotic therapy in the management of ad is best limited to treatment of an active infection, and that routine post-operative use of a topical antibiotic is not suggested after most officebased dermatologic procedures. over time, the collective benefit of dermatologists complying with principles of antibiotic stewardship as best as possible will assist in reducing the challenges clinicians face related to antibiotic resistance. conflict of interest disclosures: dr. del rosso is a consultant, investigator, and/or speaker for allergan, aqua/almirall, bayer, biopharmx, celgene, cipher (innocutis), cutanea, dermira, ferndale, foamix, galderma, genentech, innovaderm, leopharma, novan, pfizer (anacor), pharmaderm, promius, regeneron, sanofi/genzyme, sebacia, sunpharma, taro, unilever, valeant (ortho dermatologics), and viamet. this article was developed and written solely by the author. the author did not receive any form of compensation, either directly or indirectly, from any company or agency related to the development, authorship, or publication of this article. funding: none. corresponding author: james q. del rosso, do jdr dermatology research 9080 west post road suite 100 las vegas, nevada 89148 702-331-4123 jqdelrosso@yahoo.com references: 1. dreno b, thiboutot d, gollnick h, et al. antibiotic stewardship in dermatology: limiting antibiotic use in acne. eur j dermatol. 2014;24(3):330–334. 2. del rosso jq. report from the scientific panel on antibiotic use in dermatology: introduction. cutis. 2007;79(6s):6–8. 3. leyden jj, del rosso jq, webster gf. clinical considerations in acne vulgaris and other inflammatory skin disorders: focus on 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in cutaneous propionibacteria clinically relevant? implications of resistance for acne patients and prescribers. am j clin dermatol. 2003;4(12):813–831. 27. goossens h. antibiotic consumption and link to resistance. clin microbiol infect. 2009;15(suppl 3):12–15. 28. seppala et al. the effect of changes in the consumption of macrolide antibiotics on erythromycin resistance in group a streptococci in finland. finnish study group for antimicrobial resistance. n engl j med. 1997;337(7): 441–446. 29. bergman m, huikko s, pihlajamäki m, et al. effect of macrolide consumption on erythromycin resistance in streptococcus pyogenes in finland in 1997–2001. clin infect dis. 2004;38(9):1251–1256. 30. steinhoff m, buddenkotte j, aubert j, et al. clinical, cellular, and molecular aspects in the pathophysiology of rosacea. j investig dermatol symp proc. 2011; 15:2–11. 31. two am, wu w, gallo rl, et al. rosacea: part i. introduction, categorization, histology, pathogenesis, and risk factors. j am acad dermatol. 2015;72:749-758. 32. schwab vd, sulk m, seeliger s, et al. neurovascular and neuroimmune aspects in the pathophysiology of rosacea. j investig dermatol symp proc. 2011;15:53-62. 33. del rosso jq. advances in understanding and managing rosacea: part 1: connecting the dots between pathophysiological mechanisms and common clinical features of rosacea with emphasis on vascular changes and facial erythema. j clin aesthet dermatol. 2012;5(3):16-25. 34. yamasaki k, gallo rl. the molecular pathology of rosacea. j dermatol sci. 2009;55:77-81. 35. del rosso jq, gallo rl, tanghetti e, et al. an evaluation of potential correlations between pathophysiologic mechanisms, clinical manifestations, and management of rosacea. cutis. 2013;91(3s):1-7. 36. steinhoff m, schmelz m, schauber j. facial erythema of rosacea – aetiology, different pathophysiologies, and treatment options. acta venereol. 2016;96:579-86. 37. del rosso jq, thiboutot d, gallo r, et al. consensus recommendations from the american acne & rosacea society on the management of rosacea, part 5: a guide on the management of rosacea. cutis. 38. korting hc, schollmann c. tetracycline actions relevant to rosacea treatment. skin pharmacol physiol. 2009;22(6):287-294. 39. webster gf, del rosso jq. antiinflammatory activity of tetracyclines. dermatol clin. 2007;25(2):133-135. 40. del rosso jq. a status report on the use of sub-antimicrobial dose doxycycline: a review of athe biologic and antimicrobial effects of the tetracyclines. cutis. 2004;74(2):118-122. 41. coda ab, hata t, miller j, et al. cathelicidin, kallikrein 5, and serine protease activity is inhibited during treatment of rosacea with azelaic acid 15% gel. j am acad dermatol. 2013; 69:570–7. 42. schaller m, gonser l, belge k, et al. dual anti-inflammatory and anti-parasitic action of topical ivermectin 1% in papulopustular rosacea. j eur acad dermatol venereol. 2017 jun 27. doi: 10.1111/jdv.14437. [epub ahead of print] skin september 2017 volume 1 issue 2 copyright 2017 the national society for cutaneous medicine 72 43. casas c, paul c, lahfa m, et al. quantification of demodex folliculorum by pcr in rosacea and its relationship to skin innate immune activation. exp dermatol. 2012; 21:906–10. 44. del rosso jq, baldwin h, webster g, et al. american acne & rosacea society rosacea medical management guidelines. j drugs dermatol. 2008;7(6):531-533. 45. asai y, tan j, baibergenova a, et al. canadian clinical practice guidelines for rosacea. j cut med surg. 2016;20(5):432-445. 46. schaller m, schofer h, homey b, et al. rosacea management: update on general measures and topical treatment options. j dtsch dermatol ges. 2016;14(suppl 6):1727. 47. mikkelsen cs, holmgren hr, kjellman p, et al. rosacea: a clinical review. dermatol reports. 2016;8:6387. 48. del rosso jq, kircik lh. update on the management of rosacea: a status report on the current role and new horizons with topical azelaic acid. j drugs dermatol. 2014;13(12):s101-107. 49. siddiqui k, stein gold l, gill j. the efficacy, safety, and tolerability of ivermectin compared with current topical treatments for the inflammatory lesions of rosacea: a network meta-analysis. springerplus. 2016;5(1):1151. 50. del rosso jq, et al. consensus recommendations from the american acne & rosacea society on the management of rosacea, part 3: a status report on systemic therapies. cutis. 2014;93(1):18-28. 51. hon kl, tsang yc, pong nh. clinical features and staphylococcus aureus colonization/infection in childhood atopic dermatitis. j dermatolog treat. 2016;27(3):235–240. 52. hirschmann jv. when antibiotics are unnecessary. dermatol clin. 2009;27(1):75– 83. 53. breuer k, haussler s, kapp a, et al. staphylococcus aureus: colonizing features and influence of an antibacterial treatment in adults with atopic dermatitis. br j dermatol. 2002;147(1):55–61. 54. neimann al, lipoff j, garner r, et al. the role of infectious agents in atopic dermatitis. in: rudikoff d, cohen sr, scheinfeld n, eds. atopic dermatitis and eczematous disorders. boca raton, florida: crc press; 2014:164– 177. 55. nilsson ej, henning cg, magnusson j. topical corticosteroids and staphylococcus aureus in atopic dermatitis. j am acad dermatol. 1992;27:29–34. 56. stalder jf, fleury m, sourisse m, et al. local steroid therapy and bacterial skin flora in atopic dermatitis. br j dermatol. 1994;131:536–540. 57. del rosso jq, levin j. the clinical relevance of maintaining the functional integrity of the stratum corneum in both healthy and disease-affected skin. j clin aesthet dermatol. 2011;4(9):22–42. 49 58. saco m, howe n, nathoo r, et al. topical antibiotic prophylaxis for prevention of surgical wound infections from dermatologic procedures: a systematic review and metaanalysis. j dermatolog treat. 2015;26(2):151–158. 59. smack dp, harrington ac, dunn c, et al. infection and allergy incidence in ambulatory surgery patients using white petrolatum vs skin september 2017 volume 1 issue 2 copyright 2017 the national society for cutaneous medicine 73 bacitracin ointment. a randomized controlled trial. jama. 1996;276(12):972–977. 60. dixon aj, dixon mp, dixon jb. randomized clinical trial of the effect of applying ointment to surgical wounds before occlusive dressing. br j surg. 2006;93(8):937–943. 61. wright ti, baddour lm, berbari ef, et al. antibiotic prophylaxis in dermatologic surgery: advisory statement 2008. j am acad dermatol. 2008;59(3):464–473. skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 90 brief articles subcutaneous panniculitis-like t-cell lymphoma: a mixed diagnostic approach to diagnosing a vague clinical picture callie r hill, bs,1 apphia wang, md1 boni e elewski, md1, peter g pavlidakey, md1 1department of dermatology, university of alabama at birmingham, birmingham, al subcutaneous panniculitis-like t-cell lymphoma (sptcl) is a rare disease, accounting for less than 1% of non-hodgkin’s lymphomas, that is characterized by infiltration of t-cells in the subcutaneous adipose tissue typically without lymph node involvement.1, 2 it was first described in 1991, and was later accepted as a distinct disease by the world health organization in 2001.3, 4 sptcl classically follows an indolent clinical course with good prognosis.4 associated symptoms are commonly constitutional and nonspecific, including fever, weight loss, and fatigue. however, more severe symptoms, including central nervous system involvement and hemophagocytic syndrome, have also been reported and associated with poorer prognosis.5, 6 physical exam findings typically reveal multiple subcutaneous nodules or plaques, most commonly located on the trunk or extremities, that can be associated with other features such as pain, erythema, warmth, and induration.5, 7 sptcl subcutaneous panniculitis-like t-cell lymphoma (sptcl) is a rare subtype of cutaneous tcell lymphoma, and it has been associated with a range of clinical symptoms from mild to severe. most commonly, this disease is described as following a slowly progressing course, associated with vague constitutional symptoms and good prognosis. this case report describes the clinical presentation and findings of sptcl in a 31 year old female and describes the challenges of recognizing and properly diagnosing this disease. sptcl has been described as a mimicker of other, more common and nonmalignant diseases of the skin, such as lupus panniculitis. this report highlights a variety of specific tests including immunohistochemical and immunoperoxidase staining, as well as genotypic analysis of tcell receptors, that were effective in combination in isolating this diagnosis. moreover, choice of treatment for these patients can be challenging, as an array of interventions have been described in past cases to treat sptcl. this report recognizes the efficacy of a treatment course that included a six-cycle course of combined chemotherapy (vincristine, doxurubicine, cyclophosphamide, and prednisone, also known as chop) followed by weekly methotrexate and pet scan surveillance for two years. with both initial and maintenance therapy, this patient showed excellence response evidenced by a progressive decrease in metabolic activity of malignant lesions, lack of new lesions, and remaining without symptoms. while this disease is rare, it is important to include sptcl in the differential when considering patients with a panniculitic picture. abstract introduction skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 91 can be difficult to discern from more common skin conditions including cellulitis, psoriasis, benign panniculitis, and other soft tissue inflammatory conditions.7 to make this challenging diagnosis, clinicians employ an assortment of specific tests that go beyond histopathological findings and exploit the immunophenotypic and genotypic qualities of t-cell receptors in the subcutaneous tissue. 6 treatment approaches for sptcl are also quite variable and patient-specific, often taking into consideration factors of local versus diffuse disease, pathologic features, and severity of symptoms.8 a 31-year-old african american female presented with a two-year history of tender, enlarging subcutaneous nodules of her right breast and arm. she reported them as initially dime-sized and painless, but became progressively tender as they grew in size. she denied history of fever, weight loss, rashes, patchy alopecia, photosensitivity, raynaud’s phenomenon, xerostomia, nasal or oral ulcers, dysphagia, muscle weakness, or thrombotic events. she denied history of local trauma, chronic pancreatitis, recent travel, sick contacts, or animal bites when nodules first appeared. physical exam was performed and significant for a warm, indurated subcutaneous mass measuring 4 cm and localized to the outer upper quadrant of the right breast. similar areas of induration were noted along the dorsal aspect of the right upper arm (fig 1), and the inner upper quadrant of the left breast. complete blood count, metabolic panel, and rheumatologic labs were drawn. investigators found a leukopenia of 3.90× 109/l (normal range, 4.5 11.0 × 109/l) and mildly elevated rnp/sm: 25 units (normal < 20 units). serologic workup was negative for lupus anticoagulant and rheumatologic labs: ana, scl, anti-dna, anti-sm, anca, mpo, ace, and beta-glycoprotein. chest x-ray was unremarkable. punch biopsy from a right chest nodule showed an atypical panniculitic infiltrate most consistent with subcutaneous panniculitislike t-cell lymphoma (fig 2). a cd123 immunostain highlighted diffuse numbers of plastacytoid dendritic cells. immunohistochemical staining of cd8+ was notable for neoplastic cells rimming numerous adipocytes. a tcr beta f1 also highlighted neoplastic cells. immunoperoxidase staining of ki-67 also appreciated high numbers of lymphocytes rimming adipocytes (fig 3). figure 1: 3-4 cm indurated, erythematous plaque of the right proximal arm. case report skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 92 in addition, genotypic analysis of t-cell receptor (tcr) gene rearrangement by pcr assay was positive for clonal peaks (fig 4). examination of the clinical picture, in conjunction with histopathological evidence, immunohistochemical staining, and genotypic analysis led to the diagnosis of subcutaneous panniculitis-like t-cell lymphoma. initial staging with whole body pet/ct showed a large fdg cutaneous and subcutaneous lesion of the right breast with extension into the pectoralis major muscle and another intensely hypermetabolic lesion of the right arm consistent with active lymphoma. in addition, hypermetabolic adenopathy of the right axilla and left external iliac and inguinal nodes was shown. the patient was started on a combination therapy of vincristine, doxurubicine, cyclophosphamide, and prednisone, also commonly known as chop. the patient completed six cycles of chop therapy and was started on weekly maintenance therapy with methotrexate. pet imaging in the following two years showed an interval decrease in hypermetabolic activity of the existing subcutaneous masses and without occurrence of new lesions. figure 2: histopathological findings: skin, right chest, punch biopsy: atypical panniculitic infiltrate consistent with subcutaneous panniculitis-like t-cell lymphoma. figure 3: targeted ki-67 study highlighting high numbers of lymphocytes (top) and cd8 staining showing neoplastic cells (bottom) reaming numerous adipocytes. sptcl is a rare disease that typically follows an indolent clinical course, first described by gonzalez and colleagues in 1991.3, 9 the world health organization-european organization for research and treatment of cancer (who-eortc) classifies sptcl as an indolent subtype of cutaneous t-cell lymphoma (ctcl).10 using data from 1476 patients registered by dutch and austrian cutaneous lymphoma groups, sptcl was found to have a frequency and 5-year survival of 1% and 82%, respectively.10 this disease is easily misdiagnosed due to its strong histological and clinical resemblance discussion skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 93 figure 4 (a-c): t-cell gene rearrangement showing clonal peaks with intensity consistent with clonal neoplasms. a: clonal peaks migrating at 190 bases on t-cell receptor gamma b: clonal peaks at 254 bases (vbeta + jbeta, tube a) c: clonal peak at 278 bases (dbeta + jbeta, tube c) on t-cell receptor beta to nonmalignant panniculitis, such as lupus panniculitis.11, 12 sptcl is a cytotoxic t-cell lymphoma derived from α/β t-cells within subcutaneous tissue and commonly cd8+ and cd56-.10, 1316 this is an important distinction, as cases of ctcl with ϒ/δ t-cell phenotype typically represent a more aggressive clinical course with distinctly different immunophenotypical and histological characteristics. therefore, sptcl has been reserved for cases with α/β phenotypes, whereas ϒ/δ phenotypes are now classified as primary cutaneous ϒ/δ tcell lymphomas.10 the mechanism by which tumor cells migrate to subcutaneous tissue in sptcl is not understood; however, the pathology of sptcl may be related to chemokine receptors on tumor cells. one group recognized the expression of ccr4 and ccr5 on neoplastic t-lymphocytes of a patient with sptcl. furthermore, these receptors were proposed to play a role in promoting the recruitment, migration, and expansion of malignant lymphocytes in the subcutaneous tissue.16 this disease is most common in young adults, with an increased predominance in women.14 patients typically present with multiple subcutaneous nodules or plaques, with the most common locations being the extremities or trunk.11, 17 unique to this patient’s case is the occurrence of nodules on the breast. the spectrum of associated clinical symptoms is otherwise nonspecific in sptcl. interestingly, while not reported in this patient, fever of unknown origin is a common symptom reported to precede the diagnosis of sptcl.18 weight loss and fatigue may herald a more rapidly progressive syndrome; however, involvement extending beyond cutaneous tissue is still rare.19 facial swelling has also been reported in some cases.20, 21 in addition, hemophagocytosis (hps), pancytopenia, coagulopathy, and hepatosplenomegaly have been reported on rare instances of sptcl. hps is a result of t cell overproduction of cytokines (interferon-ϒ, il2, il-6, il-12, il-18 and tumor necrosis factor-alpha) and is associated with poorer prognosis. 8, 15, 22, 23 radiologic imaging has been used in the initial work-up and detection of disseminated sptcl. in similar case reports describing sptcl diagnosed in breast tissue, radiologic findings have ranged from ill-defined hyperdensity to calcifications suggestive of fat necrosis. seo et al described a patient with similar presenting features of subcutaneous breast nodule and skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 94 mammographic findings of increased opacity without calcifications or architectural distortion. this patient was also initially diagnosed with lupus panniculitis.17 architectural distortion and asymmetrical density with “flakelike” calcifications suggesting fat necrosis has also been described 24. radiologic imaging has not only been used to detect disseminated or extracutaneous sptcl, but also to determine treatment response.2 as seen in this case, pet/ct whole body initial staging showed fdg hypermetabolic areas of the breast and upper arm consistent with active lymphoma. there has been a reported case of sptcl in which fluorine-18 fluorodeoxyglucose (f-18 fdg) pet/ct showed enhancing subcutaneous nodules with an infiltrative pattern throughout the body and following three cycles of chop therapy, a total remission of metabolically active lesions in repeat f-18 fdg pet/ct of their patient was demonstrated.1 biopsy for histopathological interpretation is commonly performed as a first step in diagnosis. a predominant infiltrate of small, hyperchromatic cells with irregularly shaped nuclei are characteristic, as well as neoplastic cells rimming adipocytes are typically seen.19, 20 t-cells of this disease characteristically have immunohistochemical phenotype of cd3+, cd4-, cd8+, cd56-, and tcr+.2 as seen in this patient, diagnostic testing showing cd8+ and ki-67 was useful in identifying neoplastic cells rimming adipocytes.8 this feature was described in the original case of sptcl by gonzalez and colleagues.3 one study recognized this phenomenon in 16 cases of sptcl, noting it to be a helpful diagnostic tool in identifying the disease. however, while helpful, this finding is not specific to sptcl, as it can be found in other cases of lobular panniculitis, as well as primary and secondary cutaneous lymphomas.12 first interpretation of the biopsy from our patient was read as mixed septal and lobular panniculitis, prompting an initial diagnosis of lupus panniculitis. still, with histopathology alone, our clinicians were unable to firmly rule out t-cell lymphoma. for this reason, more precise tests were warranted. the finding of diffuse numbers of plastacytoid dendritic cells with immunohistochemical staining for cd123 in our patient was notable, as this phenomenon has been observed in both sptcl and lupus erythematous profundus (lep). one study found an overlap of both sptcl characteristics of lymphocytes rimming adipocytes as well as other areas of b-cell nodules arranged peripherally to fat lobules resembling lep histopathology. therefore, as in this patient, lep is a potential mimic for sptcl. another hypothesis suggests lep and sptcl could be two ends of one disease spectrum.25 tcell receptor gene rearrangement analysis, as applied in this case, has shown significance in the diagnosis of malignant lymphomas.10, 26, 27 while this study is useful in detecting clonal t-cell populations in patients with t-cell lymphomas, they can also be seen in other benign conditions such as pleva, lichen sclerosis, lichen planus, and some pseudolymphomas. therefore, it is important to recognize the use of these tests in conjunction with clinical and histologic findings when arriving at a diagnosis of sptcl.10 standardized therapy guidelines have yet to be established for this disease. this patient showed an excellent response to six cycles of chop therapy evidence by decreased hypermetabolic activity on pet surveillance. she continued to show improvement and remain asymptomatic with weekly methotrexate maintenance over the following two years. a wide variety of therapies have been used in the treatment of sptcl, skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 95 including radiotherapy, chop (cyclophosphamide, hydroxydaunorubicin, vincristine and prednisolone), auto/allo-stem cell transplant, cyclosporine, high dose steroids, as well as other derivations of chemotherapy regimens.8, 14 therefore, when determining therapy for these patients, consideration of factors such as extent of disease, severity of symptoms, pathologic features, and response to past treatments is important. in the few case reports describing breast involvement of sptcl, treatment regimens including chop and local radiotherapy have been found to induce remission.17 cyclosporine alone has also been reported to successfully treat sptcl with long term remission.20, 28 another group found cyclosporine, when added to chop therapy in a relapsed patient, to be efficacious in inducing long term remission.5 the primary mechanism of action of this drug is to decrease expression of cytokines.14 other clinicians have shown the effectiveness of cyclosporine in treating relapsed sptcl that was refractory to anthracycline based chemotherapy, but question its efficacy as first line treatment.26, 28 another consideration, in patients with severe systemic symptoms, is to combine cyclosporine with high dose steroids.20 one group noted complete clinical remission with monotherapy of corticosteroids in a pregnant patient.29 therefore, when considering therapy, risks and benefits of certain therapies should be weighed for each patient. when considering recurrent or refractory disease, a wide variety of salvage chemotherapies and treatment modalities have been explored. in regards to chop therapy, one group found gemcitabine, cisplatin, and methylprednisolone (gem-p) to be efficacious in a patient refractory to chop.8 the effectiveness of stem cell transplation in patients with refractory or recurring sptcl has been reported in several cases.15, 30, 31 as this case demonstrates, the clinical presentation, diagnostic approaches, and therapies for sptcl are not straightforward. it is important that sptcl is ruled out when considering other non-malignant, panniculitis-like pictures. careful attention to histopathological evidence should be combined with approaches such as immunohistochemical staining and genotypic studies to further distinguish this disease. a large-volume patient study is warranted to determine standardized approaches to therapy as it relates to extent of disease, pathologic features, and history of relapse. moreover, a small number of case reports have found value in fdg-ct/pet imaging to identify distribution, morphological patterns, metabolic activity, and treatment response of sptcl. therefore, use of this imaging modality could be helpful in both the preand posttreatment setting of patients with sptcl, as well as in determining the need for maintenance therapy. conflict of interest disclosures: none. funding: none. corresponding author: callie hill uab school of medicine birmingham, al callier@uab.edu references: 1. kim, j.s., et al., usefulness of f-18 fdg pet/ct in subcutaneous panniculitislike t cell lymphoma: disease extent and treatment response evaluation. radiol oncol, 2012. 46(4): p. 279-83. conclusion mailto:callier@uab.edu skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 96 2. schramm, n., et al., subcutaneous panniculitis-like t-cell lymphoma with breast involvement: functional and morphological imaging findings. br j radiol, 2010. 83(989): p. e90-4. 3. gonzalez, c.l., et al., t-cell lymphoma involving subcutaneous tissue. a clinicopathologic entity commonly associated with hemophagocytic syndrome. am j surg pathol, 1991. 15(1): p. 17-27. 4. sugeeth, m.t., et al., subcutaneous panniculitis-like t-cell lymphoma. proc (bayl univ med cent), 2017. 30(1): p. 76-77. 5. chen, r., l. liu, and y.m. liang, treatment relapsed subcutaneous panniculitis-like t-cell lymphoma together hps by cyclosporin a. hematol rep, 2010. 2(1): p. e9. 6. shen, g., l. dong, and s. zhang, subcutaneous panniculitis-like t cell lymphoma mimicking early-onset nodular panniculitis. am j case rep, 2016. 17: p. 429-33. 7. bagheri, f., et al., an illustrative case of subcutaneous panniculitis-like t-cell lymphoma. j skin cancer, 2011. 2011: p. 824528. 8. gorodetskiy, v.r., et al., fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography evaluation of subcutaneous panniculitis-like t cell lymphoma and treatment response. world j clin cases, 2016. 4(9): p. 258-63. 9. gallardo, f. and r.m. pujol, subcutaneous panniculitic-like t-cell lymphoma and other primary cutaneous lymphomas with prominent subcutaneous tissue involvement. dermatol clin, 2008. 26(4): p. 529-40, viii. 10. bolognia, j., jorizzo, j. and schaffer, j. , dermatology. 2012, philadephia: elsevier saunders. 11. vijaya, b., m.d. sunila, and g.v. manjunath, subcutaneous panniculiticlike t-cell lymphoma: a red alert! the role of a vigilant histopathologist. indian j pathol microbiol, 2011. 54(2): p. 376-8. 12. lozzi, g.p., et al., rimming of adipocytes by neoplastic lymphocytes: a histopathologic feature not restricted to subcutaneous t-cell lymphoma. am j dermatopathol, 2006. 28(1): p. 9-12. 13. francis, a., et al., subcutaneous panniculitis-like t-cell lymphoma. indian j dermatol, 2010. 55(3): p. 2902. 14. iqbal, n. and v. raina, successful treatment of disseminated subcutaneous panniculitis-like t-cell lymphoma with single agent oral cyclosporine as a first line therapy. case rep dermatol med, 2014. 2014: p. 201836. 15. sakurai, e., et al., subcutaneous panniculitis-like t-cell lymphoma (sptcl) with hemophagocytosis (hps): successful treatment using high-dose chemotherapy (bfm-nhl & all-90) and autologous peripheral blood stem cell transplantation. j clin exp hematop, 2013. 53(2): p. 135-40. 16. kitayama, n., et al., ccr4 and ccr5 expression in a case of subcutaneous panniculitis-like t-cell lymphoma. eur j dermatol, 2017. 27(4): p. 414-415. 17. jeong, s.i., et al., subcutaneous panniculitis-like t-cell lymphoma of the breast. korean j radiol, 2013. 14(3): p. 391-4. 18. puchi silva, a., et al., [paniculitis as manifestation of prolonged febrile syndrome: case report]. rev chil pediatr, 2017. 88(3): p. 398-403. skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 97 19. james, w.d., elston, d. m., berger, t. g., & andrews, g. c. , andrews’ disease of the skin: clinical dermatology. 2011, london: saunders/elsevier. 20. asati, d.p., et al., subcutaneous panniculitis-like t-cell lymphoma with macrophage activation syndrome treated by cyclosporine and prednisolone. indian dermatol online j, 2016. 7(6): p. 529-532. 21. kosari, f. and s. akbarzadeh hosseini, local facial edema: a novel presentation of subcutaneous panniculitis-like t-cell lymphoma in a 30-year-old iranian woman. acta med iran, 2014. 52(12): p. 950-3. 22. koh, m.j., et al., aggressive subcutaneous panniculitis-like t-cell lymphoma with hemophagocytosis in two children (subcutaneous panniculitis-like t-cell lymphoma). j am acad dermatol, 2009. 61(5): p. 87581. 23. jung, h.r., et al., cyclosporine in relapsed subcutaneous panniculitislike t-cell lymphoma after autologous hematopoietic stem cell transplantation. cancer res treat, 2011. 43(4): p. 255-9. 24. sy, a.n., t.p. lam, and u.s. khoo, subcutaneous panniculitislike t-cell lymphoma appearing as a breast mass: a difficult and challenging case appearing at an unusual site. j ultrasound med, 2005. 24(10): p. 145360. 25. bosisio, f., et al., lobular panniculitic infiltrates with overlapping histopathologic features of lupus panniculitis (lupus profundus) and subcutaneous t-cell lymphoma: a conceptual and practical dilemma. am j surg pathol, 2015. 39(2): p. 206-11. 26. rojnuckarin, p., et al., cyclosporin in subcutaneous panniculitis-like t-cell lymphoma. leuk lymphoma, 2007. 48(3): p. 560-3. 27. hu, z.l., et al., subcutaneous panniculitis-like t-cell lymphoma in children: a review of the literature. pediatr dermatol, 2015. 32(4): p. 52632. 28. lee, w.s., et al., cyclosporine a as a primary treatment for panniculitis-like t cell lymphoma: a case with a longterm remission. cancer res treat, 2014. 46(3): p. 312-6. 29. west, e.s., et al., remission of subcutaneous panniculitis-like t-cell lymphoma in a pregnant woman after treatment with oral corticosteroids as monotherapy. jaad case rep, 2017. 3(2): p. 87-89. 30. ichii, m., et al., successful treatment of refractory subcutaneous panniculitislike t-cell lymphoma with allogeneic peripheral blood stem cell transplantation from hla-mismatched sibling donor. leuk lymphoma, 2006. 47(10): p. 2250-2. 31. dholaria, b., et al., relapsed subcutaneous panniculitis-like t cell lymphoma: role of haploidentical hematopoietic stem cell transplant. ann hematol, 2017. 96(12): p. 2125-2126. skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 264 clinical management recommendations oxybenzone and sunscreens: a critical review of the evidence and a plan for discussion with patients rachel s mirsky baa, giselle prado mdb, ryan m svoboda md, msc, darrell s rigel md, msd aalbert einstein college of medicine, bronx, ny bnational society for cutaneous medicine, new york, ny cduke university school of medicine, durham, nc ddepartment of dermatology, nyu school of medicine, new york, ny there has been recent extensive controversy concerning potential environmental and health hazards of oxybenzone (also known as benzophenone-3 and eusolex 4360). in july 2018, the hawaii governor signed a law prohibiting sale and distribution of sunscreens containing oxybenzone.1 the ban will go into effect in january 2021 and is intended to alleviate possible negative environmental effects of sunscreen chemicals on nearby coral reefs. although there has been widespread related media attention, there is little definitive scientific research supporting the associated concerns.1 in addition, some advocacy groups have raised worries regarding potential human health hazards of oxybenzone. given these controversies, it is critical that dermatologists have a clear understanding of the underlying issues related to oxybenzone in order to effectively counsel their patients. the purpose of this paper is to provide dermatologists with a framework for presenting this issue to patients. in-vitro experiments have found oxybenzone can cause coral bleaching at concentrations of 33-50 parts per million (ppm).2 however, these experiments created artificial conditions not reflective of actual marine reef ecosystems. additionally, they raised oxybenzone concentrations to levels much greater than those found in the ocean. to put this into perspective, water sampled off the coasts of hawaii and the us virgin islands have shown maximum oxybenzone concentrations of 0.019 and 1.4 ppm respectively – materially less than those noted in the in-vitro study and therefore unlikely to cause harm.3 environmental changes such as global warming are a more likely culprit in coral bleaching. in hawaii, water temperature more strongly correlates geographically with coral bleaching than visitor density and associated oxybenzone levels.4 the increased water temperatures promote viral infection of an important algae, zooxanthellae, that lives symbiotically on coral.2 the algae are necessary for coral to perform photosynthesis. scientists believe that coral bleaching on the great barrier reef has occurred as a direct result of increased water temperatures from global warming.5 additionally, the locations where maximal coral bleaching has occurred is oxybenzone the reason for coral bleaching? skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 265 do not correlate with where humans populate.6 there are no in-vivo studies that have shown oxybenzone to be directly causative in coral bleaching. oxybenzone has the ability to penetrate the skin, and its metabolic breakdown products are excreted in the urine. systemic absorption has been observed at a rate of 1% to 2% after topical application.7 however, the concentrations achieved by cutaneous penetration are too low to cause toxicity.8 very high levels of oxybenzone were associated with estrogenic effects in rats.9 in that study, immature rats were given extreme doses of oxybenzone orally and found to have increased uterine weights. to reach equivalent systemic concentrations of oxybenzone in humans, one would need to apply sunscreen at the fda recommended density of 2 mg/cm2 to 100% body surface area daily for 35 years.10 researchers also measured plasma concentrations of oxybenzone and reproductive hormones in men and women after application of 10% oxybenzone, finding no biologically significant differences in hormone levels.11 oxybenzone has also been suggested as a contact allergen. however, a meta-analysis of 64 studies measuring oxybenzone rates of sensitization and irritation found only 0.07% of 19,570 patients had true contact dermatitis to oxybenzone when undergoing patch testing.12 another study of 23,908 patients found only 0.9% had a patch-test-proven sunscreen allergy.13 to date, there have been no clinically significant negative effects of oxybenzone in humans. since 1978, oxybenzone has been an fda approved sunscreen agent. although there are some restrictions and labeling requirements for use in europe, it is widely used in sunscreens and other consumer products in the us.14 it has broad-spectrum coverage, successfully filtering uva (320440 nm) and uvb (290-320 nm) rays. oxybenzone has many advantages over inorganic ingredients (tio2 and zno). it is photostable, inexpensive, and easily spread on skin. consumers often prefer sunscreen formulations with organic sunscreening agents due to greater cosmetic acceptability. although inorganic sunscreens have a relatively flat uv protection spectrum, they have significant disadvantages, including minimal water-resistance, clumping, need for more frequent reapplication, and inability to achieve high spfs without being cosmetically unacceptable due to deposition of a white cast on the skin. the highest spf sunscreens often require a combination of both organic and inorganic filters to optimize uv-protection. regular sunscreen usage reduces skin cancer risk.15 hawaii has one of the highest rates of skin cancer in the us making it surprising that this state chose to implement this law. as such, the hawaii medical association, many expert dermatologists, and sunscreen manufacturers all opposed the law.1 other states may follow hawaii’s lead in banning oxybenzone. is there data to sugest that oxybenzone is harmful to humans? why is oxybenzone used in the majority of u.s. sunscreens? are there other potential problems with oxybenzone restrictions? skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 266 only 30% of sunscreens will be available to the population in hawaii leading to a potential increased future skin cancer risk in both residents and visitors.1 spray formulations of sunscreen are rapidly becoming the most popular choice of sunscreen users16 and creating oxybenzone-free versions of these products is difficult due to the inherent physical properties of inorganic sunscreen agents. patients are ill informed about sunscreen, including gaps in understanding of concepts such as “sun protection factor”, “broad spectrum”, and proper techniques of sunscreen application.17,18 additionally, little research has been done on patient knowledge of sunscreen composition. due to this knowledge gap, the most worrisome outcome is that consumers may decide to forgo sunscreen based on unfounded fears that “sunscreen is bad” and thus increase their skin cancer risk. the current state of science does not appear to justify instituting an outright ban on oxybenzone. misinformation and misinterpretation of studies that were not done in humans (such as those done on rats, in vitro, and in artificial marine ecosystems) led to this law.2,3,9 as dermatologists and physicians, we should strive to be patient centric and continue our focus on lowering skin cancer incidence and mortality. this is not to say that dermatologists are not sensitive to possible negative effects on the environment. while we encourage further research, we believe that the potential risks to patients by curtailing access to effective sunscreening agents must be seriously considered. a recently published review of the environmental effects of sunscreen ingredients concluded that potential environmental concerns alone should not detract dermatologists from continuing to educate their patients on the importance of sun protection.19 weighing a theoretical risk of coral damage versus a clear benefit from sunscreen usage and then prohibiting patients from obtaining over 70% of sunscreens is not in their benefit. given this, we suggest the following approach when discussing these issues with patients: 1) there is strong data to support sunscreen usage lowers skin cancer risk. 2) there is laboratory evidence to suggest oxybenzone has negative environmental effects, but these experiments were not representative of real-world conditions and thus results are inconclusive. 3) if a patient is concerned about possible environmental effects, they may use inorganic sunscreens, but they should be counseled about the associated disadvantages. 4) sunscreens are one part of a total sun-protection package that includes avoiding the midday sun and using sun-protective clothing. 5) the optimal sunscreen is one that patients will use consistently, keeping in mind cost and cosmetic acceptability. with the media attention given to this topic, public awareness and questions from our patients will continue to increase in magnitude. using this framework, dermatologists will be more prepared to answer patient questions, dispel how should dermatologists reconcile the science to advocate for patients? what is a reasonable approach to discuss this issue with patients? skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 267 misconceptions, and optimize sunscreen selection. conflict of interest disclosures: dr. rigel has been an investigator for neutrogena in the past. ms. mirsky, dr. prado, and dr. svoboda have no conflicts to disclose. funding: none. corresponding author: giselle prado, md national society for cutaneous medicine new york, ny 10016 drgiselleprado@gmail.com references: 1. bever l. hawaii just banned your favorite sunscreen to protect its coral reefs. washington post. jul 6, 2018. https://www.washingtonpost.com/ne ws/energyenvironment/wp/2018/07/02/hawaii -is-about-to-ban-your-favoritesunscreen-to-protect-its-coralreefs/?noredirect=on&utm_term=.d3a 78b2ef2b1. accessed jul 11, 2018. 2. danovaro r, bongiorni l, corinaldesi c, et al. sunscreens cause coral bleaching by promoting viral infections. environ health perspect. 2008;116(4):441-7. 3. downs ca, kramarsky-winter e, segal r, et al. toxicopathological effects of the sunscreen uv filter, oxybenzone (benzophenone-3), on coral planulae and cultured primary cells and its environmental contamination in hawaii and the u.s. virgin islands. arch environ contam toxicol. 2016;70(2):265-88. 4. rodgers ks, bahr kd, jokiel pl, richards donà a. patterns of bleaching and mortality following widespread warming events in 2014 and 2015 at the hanauma bay nature preserve, hawai'i. peerj. 2017;5:e3355. 5. hughes tp, kerry jt, baird ah, et al. global warming transforms coral reef assemblages. nature. 2018;556(7702):492-496. 6. bruno jf, valdivia a. coral reef degradation is not correlated with local human population density. sci rep. 2016;6:29778. 7. hayden cg, roberts ms, benson ha. systemic absorption of sunscreen after topical application. lancet. 1997;350(9081):863-4. 8. hayden cg, cross se, anderson c, saunders na, roberts ms. sunscreen penetration of human skin and related keratinocyte toxicity after topical application. skin pharmacol physiol. 2005;18(4):170-4. 9. schlumpf m, cotton b, conscience m, haller v, steinmann b, lichtensteiger w. in vitro and in vivo estrogenicity of uv screens. environ health perspect. 2001;109(3):239-44. 10. wang sq, burnett me, lim hw. safety of oxybenzone: putting numbers into perspective. arch dermatol. 2011;147(7):865-6. 11. janjua nr, mogensen b, andersson am, et al. systemic absorption of the sunscreens benzophenone-3, octylmethoxycinnamate, and 3-(4-methylbenzylidene) camphor after wholebody topical application and reproductive hormone levels in humans. j invest dermatol. 2004;123(1):57-61. 12. agin pp, ruble k, hermansky sj, mccarthy tj. rates of allergic sensitization and irritation to oxybenzone-containing sunscreen products: a quantitative meta-analysis of 64 exaggerated use studies. photodermatol photoimmunol photomed. 2008;24(4):211-7. mailto:drgiselleprado@gmail.com skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 268 13. warshaw em, wang mz, maibach hi, et al. patch test reactions associated with sunscreen products and the importance of testing to an expanded series: retrospective analysis of north american contact dermatitis group data, 2001 to 2010. dermatitis. 2013;24(4):176-82. 14. mancuso jb, maruthi r, wang sq, lim hw. sunscreens: an update. am j clin dermatol. 2017;18(5):643-50. 15. ghiasvand r, weiderpass e, green ac, lund e, veierød mb. sunscreen use and subsequent melanoma risk: a population-based cohort study. j clin oncol. 2016;34(33):3976-3983. 16. teplitz rw, glazer am, svoboda rm, rigel ds. trends in us sunscreen formulations: impact of increasing spray usage. j am acad dermatol. 2018;78(1):187-18 17. kong by, sheu sl, kundu rv. assessment of consumer knowledge of new sunscreen labels. jama dermatol. 2015;151(9):1028-30. 18. glazer am, svoboda rm, teplitz rw, et al. overcoming consumer challenges in sunscreen selection. skin – j cutan med. 2018;2(3):168-171. 19. schneider sl, lim hw. review of environmental effects of oxybenzone and other sunscreen active ingredients. j am acad dermatol. 2018; skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 317 brief articles a case of familial focal dermal hypoplasia: a report of 3 cases in consecutive generations david e. castillo mda, nicole nagrani bsa, david castillo mdb, rocio reyes muñoz mdb, mayerlis cárdenas guevara mdb, samuel d. morales mdb, anna nichols md, phda adepartment of dermatology & cutaneous surgery, university of miami miller school of medicine, miami, fl bfuninderma, fundación para la investigación en dermatología, bogotá, cundinamarca, colombia focal dermal hypoplasia (fdh), also known as goltz syndrome, is a rare genetic disorder that arises from mutations in the porcn gene.1,2 the disorder affects organs derived from ectodermal and mesodermal structures, with the skin, eyes, teeth, and musculoskeletal systems most commonly affected.3,4 the classic skin findings are linear hypopigmented papules and plaques with hyperor hypopigmentation along the lines of blaschko.4 it is known that 95% of all cases arise from novo mutations, only 5% are familial cases with an x-linked dominant inheritance pattern.3,5,6 here, we describe an uncommon presentation of 3 family members from consecutive generations with fdh. focal dermal hypoplasia (fdh), or goltz syndrome, is a rare multisystem disorder affecting mesodermal and ectodermal structures, with the skin, eyes, teeth, and musculoskeletal systems most commonly affected. fdh results from mutations in the porcn gene. ninety five percent of cases arise from novo mutations, whereas 5% are hereditary with an x-linked dominant inheritance pattern. here, we describe an uncommon presentation of fdh in three consecutive generations. patient 1 is an 8-month-old female born of non-consanguineous marriage who presented with diffuse alopecia of the scalp, linear hypopigmented, atrophic papules, and plaques with peripheral hyperpigmentation on the right hemiabdomen and right lateral leg along blaschko's lines as well as syndactyly of the right second and third toes. skin biopsy from the abdomen showed a thin epidermis with flattened rete ridges and massive dermal edema within collagen fibers and reactive capillaries. family history was significant for similar skin lesions and bone deformities in her mother and similar skin lesions in her grandmother. patient 2 (patient 1’s mother) is a 17-year-old female with similar linear hypopigmented, atrophic plaques with peripheral hyperpigmentation on the abdomen and right axilla, syndactyly of the right hand, patchy alopecia of the scalp, microdontia, teeth fusion, enamel defects, verrucous papillomas in the axillae and onycholysis. patient 3 (patient 1’s grandmother), presented with similar hypopigmented, atrophic plaques on the abdomen and left arm. abstract introduction skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 318 patient 1 is an 8-month-old female born of non-consanguineous marriage who presented with linear hypopigmented, atrophic papules and plaques with peripheral hyperpigmentation along the lines of blaschko on the right hemiabdomen and right lateral leg (figure 1a). the patient had diffuse alopecia and syndactyly of the right second and third toes (figure 1b and 1c). the nails and oral mucosa were normal. the remainder of the physical exam was normal. prenatal, perinatal, and the remainder of her medical history were unremarkable. family history was significant for similar skin lesions in both her mother and grandmother. skin biopsy from an abdominal lesion showed a thin epidermis with flattened rete ridges and massive edema in the dermis within collagen fibers and reactive capillaries (figure 2). patient 2 (patient 1’s mother) is a 17-year-old female that presented with similar skin lesions from birth. she also had dental and scalp defects as well as multiple wart-like lesions on the genital area that had been removed previously. she was born from a non-consanguineous marriage and was the youngest of three children. physical exam was significant for linear hypopigmented, atrophic plaques with peripheral hyperpigmentation following blaschko's lines on the left hemiabdomen (figure 1d) and right axilla. she had alopecia on the frontal and temporal area, microdontia, diastema with teeth fusion and enamel defects (figure 1e). further examination revealed syndactyly of the right third and fourth fingers with distal onycholysis of right fifth finger, syndactyly of the right fourth and fifth toes with distal onycholysis (figure 1f), and verrucous papillomas in the axillae. figure 1. patient 1 (8-month-old female), a: linear hypopigmented, atrophic papules and plaques with peripheral hyperpigmentation on right lateral leg. b: diffuse alopecia. c: syndactyly of the right second and third toes. patient 2 (patient 1’s mother), d: linear hypopigmented, atrophic plaques with peripheral hyperpigmentation following blaschko's lines on left hemiabdomen. e: microdontia, diastema with teeth fusion and enamel defects. f: syndactyly of the right fourth and fifth toes. patient 3 (patient 1’s grandmother), g: linear hypopigmented, atrophic plaques on left hemiabdomen along blaschko’s lines. h: linear hypopigmented, atrophic plaques on left arm. i: onychodystrophy of the left first finger. figure 2. skin biopsy from an abdominal lesion from patient 1: thin epidermis with flattened rete ridges and massive edema in the dermis within collagen fibers and reactive capillaries. case report skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 319 patient 3 (patient 1’s grandmother) is a 44year-old female with similar hypopigmented skin lesions. her past medical history was unremarkable. physical examination revealed similar hypopigmented, atrophic plaques on left hemiabdomen and left arm (figure 1g and 1h), and onychodystrophy of the left first finger (figure 1i). there were no mucosal, scalp or musculoskeletal findings. focal dermal hypoplasia (fdh), or goltz syndrome, is a rare genetic disorder resulting from mutations in the porcn gene. this multisystem disease affects the embryonic development of ectodermal, mesodermal, and endodermal tissues resulting in a wide range of abnormalities with variable expression.7 when hereditary, fdh is inherited in an x-linked dominant pattern with mosaic distribution in affected tissues [7]. the mutations in the porcn gene located on the x chromosome result in disruption of wnt signaling.8 ninety percent of patients with fdh are female, 95% of those are due to new mutations, 5% are inherited, and affected individuals may be heterozygous or mosaic.1,5,6 non-mosaic male porcn pathogenic variants are presumed to be lethal2; therefore, post-zygotic mosaicism allows males with fdh to overcome this consequence. there have been reports of “pseudo-anticipation” in fdh where the affected parent has milder symptoms than that observed in the affected child as was seen in our case series.9 the clinical presentation of fdh is often variable, making diagnosis difficult. the characteristic skin manifestations include hypopigmented or depigmented macules with patchy skin hypoplasia and hyperpigmentation following blaschko’s lines or with a reticulated configuration.2 telangiectasias interspersed between the atrophic plaques are also commonly observed. these features can be present at birth initially as blisters or erosions that heal with atrophic scars anywhere on the body.7 there have been reports of xerosis, photosensitivity, lipomatous hamartomas, and pruritus within these atrophic areas.10 the dermal defects permit fat herniation, which appears as soft, pink-brown nodules overlying the thin atrophic skin.7 additional cutaneous findings include fibrovascular papillomas which can also arise on mucous membranes, particularly the perineal, vulvar, and perianal regions, and often manifest later in life.1,11 laryngeal and esophageal papillomas have also been described.1 fdh may cause ridged, dysplastic, or hypoplastic nail, and hair growth can be sparse or completely absent leading to diffuse or patchy alopecia.11 extra-cutaneous involvement varies and involves multiple organs and systems. manifestations of fdh in the eye include iris or chorioretinal colobomas, microphthalmia or anophthalmos, lacrimal duct abnormalities, cataracts, nystagmus, and strabismus.11 when genetic testing is not available, as in this case, clinical evaluation is generally sufficient to establish a diagnosis. bostwick et. al proposed diagnostic criteria for fdh including three or more characteristic skin findings and one or more characteristic limb malformations. skin findings must be congenital in onset, which helps differentiate fdh from rothmund-tomson syndrome, which presents with a similar cutaneous phenotype including patchy skin aplasia, nodular fat herniation, hyperor hypopigmentation along blaschko’s lines, telangiectasias, and nail abnormalities.11 limb abnormalities seen in fdh include split hand/foot, transverse limb defects (ectrodactyly), syndactyly, oligodactyly, and marked long bone reduction.11,12 discussion skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 320 we present a rare case series of familial fdh in three consecutive generations. the diagnosis was based on clinical and histopathological features. the clinical presentation of patient 2 and patient 3 illustrates the “pseudo-anticipation” phenomenon and predicts that patient 1 may manifest additional features of fdh later in life and thus should be monitored by a multidisciplinary team including but not limited to a dermatologist, orthopedist, ophthalmologist, and dentist. the goal of treatment is to improve functionality and quality of life. conflict of interest disclosures: none. funding: none. corresponding author: david e. castillo, md department of dermatology & cutaneous surgery university of miami miller school of medicine miami, fl 33136 e-mail: dxc925@miami.edu references: 1. goltz, r.w., focal dermal hypoplasia syndrome. an update. arch dermatol, 1992. 128(8): p. 1108-11. 2. bostwick, b., et al., phenotypic and molecular characterization of focal dermal hypoplasia in 18 individuals. am j med genet c semin med genet, 2016. 172c(1): p. 9-20. 3. wang, l., et al., focal dermal hypoplasia: updates. oral dis, 2014. 20(1): p. 17-24. 4. severino-freire, m., et al., mosaic focal dermal hypoplasia (goltz syndrome) in two female patients. acta derm venereol, 2017. 97(7): p. 853-854. 5. mary, l., et al., prenatal diagnosis of focal dermal hypoplasia: report of three fetuses and review of the literature. am j med genet a, 2017. 173(2): p. 479-486. 6. wang, x., et al., mutations in x-linked porcn, a putative regulator of wnt signaling, cause focal dermal hypoplasia. nat genet, 2007. 39(7): p. 836-8. 7. jain, a., et al., a rare multisystem disorder: goltz syndrome case report and brief overview. dermatol online j, 2010. 16(6): p. 2. 8. bornholdt, d., et al., porcn mutations in focal dermal hypoplasia: coping with lethality. hum mutat, 2009. 30(5): p. e618-28. 9. sellars, e.a., et al., variable presentation between a mother and a fetus with goltz syndrome. prenat diagn, 2013. 33(12): p. 1211-3. 10. bree, a.f., et al., dermatologic findings of focal dermal hypoplasia (goltz syndrome). am j med genet c semin med genet, 2016. 172c(1): p. 44-51. 11. bostwick, b., i.b. van den veyver, and v.r. sutton, focal dermal hypoplasia, in genereviews(r), m.p. adam, et al., editors. 1993: seattle (wa). 12. smith, a. and t.r. hunt, 3rd, the orthopedic characterization of goltz syndrome. am j med genet c semin med genet, 2016. 172c(1): p. 41-3. mailto:dxc925@miami.edu distribution of depression and suicidality in a psoriasis clinical trial population steven r. feldman,1 susan harris,2 shipra rastogi,3 robert j. israel2 1wake forest university school of medicine, winston-salem, nc; 2valeant pharmaceuticals north america llc, bridgewater, nj; 3ortho dermatologics, bridgewater, nj winter clinical dermatology conference hawaii® • january 12-17, 2018 • lahaina, hi synopsis • patients with psoriasis have an increased risk of depression and suicidal ideation and behavior (sib)1,2 • brodalumab is a fully human anti–interleukin-17 receptor a monoclonal antibody that antagonizes the action of specific inflammatory cytokines involved in psoriasis3 • one multicenter, randomized, placebo-controlled phase 3 trial (amagine-1), 2 multicenter, randomized, placebo and active comparator–controlled phase 3 trials (amagine-2/-3), and one phase 2 trial demonstrated the efficacy and safety of brodalumab in patients with moderate-to-severe psoriasis3-5 • all regions involved in the trials reported baseline rates of depression and sib • rates of sib events were low throughout all trials (range, 0 to 0.77 per 100 patient-years [py]) objective • this analysis evaluated rates of depression adverse events (aes) and sib in patients participating in one phase 2 and three phase 3 clinical trials of brodalumab methods study design • pooled data for all trials in patients who received any dose of brodalumab are included • of note, the brodalumab trials had no exclusions based on the presence or history of psychiatric disorders or substance abuse endpoints/assessments • rates of depression aes and sib (intentional self-injury, suicidal behavior, suicide attempt, and completed suicide) in the united states, canada, europe, australia, and russia were assessed at baseline and throughout the trials results patient demographics and baseline disease characteristics • a total of 4464 patients received brodalumab, with cumulative exposure times of 3672.6 py in the us (n=1937), 1473.4 py in canada (n=631), 3492.7 py in europe (n=1651), 388.8 py in australia (n=180), and 134.4 py in russia (n=65) safety • at baseline, depression was observed across most study regions, which is representative of the psoriasis population (figure 1) • depression ae rate in py from the first dose of brodalumab through end of study was also consistent across regions (figure 2) • sib was observed at baseline across all countries involved in the 4 trials (figure 3) • follow-up observation time-adjusted incidence rates of sib events from the first dose of brodalumab through end of study were consistent across regions (figure 4) acknowledgments: medical writing support was provided by medthink scicom and was funded by ortho dermatologics. this study was sponsored by amgen inc. author disclosures: the authors disclose past or current financial relationships with the following companies: feldman – abbvie, advance medical, almirall, anacor, astellas, baxter, boehringer ingelheim, caremark, celgene, cosmederm bioscience, galderma, glaxosmithkline/stiefel, informa, janssen, leo pharma, eli lilly & co, merck, merz, mylan, national biological corporation, national psoriasis foundation, novan, novartis, parion, pfizer, qurient, regeneron, suncare research, taro, uptodate, valeant pharmaceuticals north america llc, gerson lehrman, guidepoint global, www.drscore.com, and causa research; harris – valeant pharmaceuticals north america llc; israel – valeant pharmaceuticals north america llc; and rastogi – ortho dermatologics and valeant pharmaceuticals north america llc. references: 1. kurd skk et al. arch dermatol. 2010;146:891-895. 2. koo j et al. j eur acad dermatol venereol. 2017 [epub ahead of print]. 3. lebwohl m et al. n engl j med. 2015;373:1318-1328. 4. papp ka et al. br j dermatol. 2016;175:273-286. 5. papp ka et al. n engl j med. 2012;366:1181-1189. conclusions • clinical trials of brodalumab reflected real-world populations of patients with moderate-to-severe psoriasis • the patients in these 4 trials had baseline rates of depression and sib that were consistent with those in other studies2 • the follow-up observation time-adjusted incidence rates (per 100 py) of sib events from the first dose of brodalumab through end of study were consistent across regions © 2017. all rights reserved. 5.7% 0% 22.7% 20% 18.6% figure 1. incidence of depression at baseline across geographic regions in patients who received any dose of brodalumab in any of the 4 trials. number of patients who had valid measurements at baseline: united states, 1937; canada, 631; europe, 1651; australia, 180; and russia, 65. in ci de nc e ra te o f s ib pe r 10 0 pa ti en tye ar s 3 0 2 1 5 4 0.52 united states 0.14 canada 0.29 europe 0.77 australia 0 russia figure 4. follow-up observation time-adjusted incidence rates (per 100 patient-years) of sib events from the first dose of brodalumab through end of study in patients from the long-term extension of any of the 4 trials. sib, suicidal ideation and behavior. total patient-year exposure for each region: united states, 3672.6; canada, 1473.4; europe, 3492.7; australia, 388.8; and russia, 134.4. t im ead ju st ed d ep re ss io n ad ve rs e ev en t ra te pe r 10 0 pa ti en tye ar s 3 0 2 1 5 4 2.8 united states 2.9 canada 1.6 europe 4.6 australia 1.5 russia figure 2. depression adverse event rate in patient-years from the first dose of brodalumab through end of study. total patient-year exposure for each region: united states, 3680.9; canada, 1473.5; europe, 3496.3; australia, 388.9; and russia, 134.4. 1.8% 3.1% 6.7% 2.8% 3.8% figure 3. incidence of baseline sib across geographic regions in patients who received any dose of brodalumab in any of the 4 trials. sib, suicidal ideation and behavior. number of patients who had valid measurements at baseline: united states, 1937; canada, 631; europe, 1651; australia, 180; and russia, 65. skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 608 brief articles a rapidly enlarging solitary infantile myofibroma: a case report and a review of current monitoring guidelines stephany vittitow, ba1, merrick d. kozak, md2, reza j. daughtery, md3, barrett j. zlotoff, md2 1university of virginia school of medicine, charlottesville, va 2university of virginia department of dermatology, charlottesville, va 3university of virginia department of radiology, charlottesville, va infantile myofibromatosis (im) is a mesenchymal disorder characterized by a fibrous proliferation that can affect the skin, bones, muscle and viscera. once classified as fibroblastic/myofibroblastic in origin, these neoplasms have recently been reclassified as pericytic tumors.1 there are three distinct clinical subtypes of im: solitary, multicentric without visceral involvement, and multicentric with visceral involvement (generalized).2 im usually presents before age two, with 50% of solitary forms and 90% of multicentric forms being congenital.2,3 the remaining 50% of solitary forms may present in older children and adults and tend to have a better prognosis.2,3 the estimated incidence of im is between 1 in 150,000 to 400,000 live births.4 typically, im presents as a firm, subcutaneous nodule on the head and neck. imaging is mandatory, in order to assess for multicentric and visceral disease, as both morbidity and mortality increase with more extensive involvement. a 6-week-old caucasian male with a history of a congenital violaceous nodule on the left occipital scalp presented to the emergency department after the lesion rapidly increased in size and subsequently ulcerated. the mass drained copious amounts of foulsmelling, purulent discharge. the patient’s mother reported a measured fever of 101.7 degrees fahrenheit, vomiting, and fussiness. he was given a dose of acetaminophen and ceftriaxone at an outside emergency department prior to transfer to our facility. physical examination revealed a 5cm x 5.5cm firm, non-fluctuant, violaceous nodule with overlying abstract infantile myofibromatosis is a rare disorder of mesenchymal cell proliferation that can affect the skin, bone, muscle, and viscera. we present a case of a 6-week-old male with a rapidly enlarging congenital solitary infantile myofibroma. the differential for congenital tumors of the head and neck is broad, and thorough evaluation is required to rule out life-threatening malignancy. currently, there is no first-line imaging modality of choice to assess for skeletal and/or visceral involvement in patients with infantile myofibromatosis. we recommend the use of whole-body magnetic resonance imaging (mri), as it quickly provides detailed information regarding extent of disease and does not expose the patient to the harmful effects of radiation. introduction case presentation skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 609 figure 1. violaceous 5cm nodule with overlying hemorrhagic crust on the left occipital scalp. hemorrhagic crust (figure 1). there was no occipital or posterior cervical adenopathy. the remainder of the examination was unremarkable. a complete blood count was notable for a white blood cell count of 15.9 x 109/l and a platelet count of 673 x 109/l. grey scale and doppler ultrasound were nondiagnostic. non-contrast computed tomography (ct) revealed no evidence of erosion of the mass into the occipital bone (figure 2a-d). histological examination revealed a dermal proliferation of spindled cells with elongated oval nuclei and indistinct eosinophilic cytoplasmic borders. the spindled cells were arranged in short fascicles intermixed with thin strands of collagen bundles. nuclear pleomorphism and mitotic activity were absent. the ki-67 proliferation index was approximately 5-10%. immunohistochemical (ihc) staining demonstrated positivity for smooth muscle actin (sma) and negativity for desmin and myogenin. (figure 3a-d). these findings confirmed a diagnosis of congenital infantile myofibromatosis. cultures returned positive for methicillin-sensitive staphylococcus aureus (mssa). further screening was recommended to rule out the presence of multicentric and visceral disease. a chest x-ray, a skeletal survey and an abdominal ultrasound demonstrated no evidence of systemic involvement (images not included). the patient underwent treatment with intravenous nafcillin and was later transitioned to oral cephalexin for a total duration of 14 days. a whole-body mri and surgical removal of the mass were recommended as an outpatient. the mass was surgically excised one month later. of the three clinical variants of im, the solitary presentation occurs predominantly in males and typically involves the dermis, subcutis, or deep soft tissues.3,5 the multicentric presentation consists of multiple lesions with involvement limited to the skin, subcutaneous tissues, muscles, and bones.6 involvement of bone has been reported in 17-77% of patients with the multicentric form, but is only seen in approximately 5% of those with solitary myofibromas.2,3 the generalized form is characterized by the involvement of the skin and viscera, which frequently results in organ failure and death.6 the differential diagnosis of congenital tumors of the head and neck is broad and includes: dermoid cyst, langerhans cell histiocytosis, rhabdomyosarcoma, fibrosarcoma, congenital hemangioma, and cutaneous neuroblastoma. due to the malignant nature of some of these entities, it discussion skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 610 figure 2. mri of the brain with contrast (a) t2 weighted sequence showing an isointense mass that is (b) hypointense on t1 and (c) shows peripheral enhancement; (d) swi demonstrates foci of low intensity suggesting internal calcifications or hemorrhage. skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 611 figure 3. (a) dermal spindled cell proliferation (h&e, 4x) (b) short fascicles of spindled cells admixed with collagen bundles. (h&e, 20x) immunohistochemical stains demonstrated positivity for smooth muscle actin (c) and negativity for desmin (d). is important that all solitary nodules on the head and neck be diagnosed promptly. definitive diagnosis can be confirmed via histopathology. surgical biopsies of infantile myofibromatosis typically demonstrate a proliferation of myofibroblasts with pale eosinophilic cytoplasm that may be arranged in whorled or interlacing fascicles.2,6 often there is a richly vascular central area that may resemble hemangiopericytomas.7 ihc staining is positive for vimentin and sma and negative for s-100, epithelial membrane antigen (ema), and cytokeratins. there is variable reactivity for desmin.6 prognosis depends on the specific variant of im. the solitary or multicentric form, in the absence of visceral involvement, is usually associated with an excellent prognosis, with spontaneous regression occurring within one to two years.2,7 the generalized variant with visceral spread carries the worst prognosis. visceral myofibromas most frequently present in the gastrointestinal tract, heart, kidneys and lungs and carry a mortality rate approaching 73%.4 involvement of the heart and lungs portend a particularly poor prognosis, as these patients often succumb to cardiopulmonary failure early in life.7 visceral disease may be treated with radical surgical excision in addition to chemotherapy and/or radiation.2,7 treatment of solitary lesions is not typically required due to the high rate of spontaneous skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 612 regression; however, conservative surgical excision may be performed to improve a patient’s quality of life if the risk for complications is minimal.6,9 due to the possibility of recurrence, follow-up is essential in all patients.6 once the diagnosis is confirmed, the determination of disease extent and progression with imaging is mandatory.7 mri has long been considered the gold standard imaging technique for soft tissue evaluation, and is particularly adept at detecting visceral involvement in im.7,10 whole-body mri enables a complete imaging survey within a short period of time and provides detailed information regarding the extent of disease and spread in contiguous organs.7 this makes it ideal to evaluate systemic involvement both initially, and every 6 months until myofibromas spontaneously regress. additionally, mri is an ideal imaging modality to use in the pediatric population, as it spares the patient from ionizing radiation.7 infantile myofibromatosis is a rare disorder, however, its consequences can be deadly. prompt diagnosis and subsequent imaging to assess for visceral involvement has the potential to reduce both morbidity and mortality. there are no formal guidelines regarding the imaging modality of choice for initial evaluation and surveillance. we suggest whole-body mri as the optimal imaging modality due to its ability to assess the skin/soft tissues, bones, and viscera without exposure to radiation. conflict of interest disclosures: none funding: none corresponding author: merrick douglas kozak, md 1221 lee street po box 300708 charlottesville va 22908 phone: 757-236-1393 email: mdk7g@virginia.edu references: 1. jo vy, fletcher cd. who classification of soft tissue tumours: an update based on the 2013 (4th) edition. pathology. 2014;46(2):95-104. 2. wu w, chen j, cao x, yang m, zhu j, zhao g. solitary infantile myofibromatosis in the bones of the upper extremities: two rare cases and a review of the literature. oncol lett. 2013;6(5):1406-1408. 3. larralde m, ferrari b, martinez jp, barbieri maf, méndez jh, casas j. infantile myofibromatosis. an bras dermatol. 2017;92(6):854-857. 4. wiswell te, davis j, cunningham be, solenberger r, thomas pj. infantile myofibromatosis: the most common fibrous tumor of infancy. j pediatr surg. 1988;23(4):315-8. 5. josephson gd, patel s, duckworth l, goldstein j. infantile myofibroma of the nasal cavity; a case report and review of the literature. int j pediatric otorhinolaryngology. 2010;74(12):1452-4. 6. mota f, machado s, moreno f, barbosa t, selores m. infantile myofibromatosis a clinical and pathological diagnostic challenge. dermatol online j. 2017;23(4) 7. salerno s, terranova mc, rossello m, piccione m, ziino o, re gl. whole-body magnetic resonance imaging in the diagnosis and follow-up of multicentric infantile myofibromatosis: a case report. mol clin oncol. 2017;6(4):579-582. 8. dachy g, de krijger rr, fraitag s, et al. association of pdgfrb mutations with pediatric myofibroma and myofibromatosis. jama dermatol. 2019; 9. maby a, guay b, thuot f. infantile myofibromatosis treated by mandibulectomy and staged reconstruction with submental flap and free fibula flap: a case report. j otolaryngol head neck surg. 2019;48(1):14. 10. counsell sj, devile c, mercuri e, allsop jm, birch r, muntoni f. magnetic resonance imaging assessment of infantile myofibromatosis. clin radiol. 2002;57(1):67-70. conclusion mailto:mdk7g@virginia.edu table 1. schedule of assessments assessment study enrollment gcm observational study informed consent x crf/clinician information form x eligibility screening x patient gcm exercise x clinician gcm exercise x patient surveys x qualitative patient interviews x group concept mapping exercise • psoriasis patients (n = 20) and clinicians (n = 10) who agree to participate in the gcm exercise will be sent a link to the globalmax platform, where they will participate in concept generation, sorting, and rating activities (figure 2; table 2). • the responses will be used to generate a qualitative representation of unmet treatment needs in psoriasis. implementation of gcm results • upon completion of the gcm exercise, the research team will interpret the gcm results and identify key research interests for the psoriasis population. analysis and interpretation will guide selection of pro measures and the development of qualitative interview topics, which will be employed in the second phase of the study. psoriasis patient survey • the remaining psoriasis patients (n = 100) will be surveyed for the pro measures directly aligned with the research questions and concepts elicited in the gcm exercise. 1. langley rb, krueger gg, griffiths ce. psoriasis: epidemiology, clinical features, and quality of life. ann rheum dis 2005;64(suppl 2):ii18-ii23. 2. mayo clinic staff. diseases and conditions psoriasis. mayo clinic. available at: http://www.mayoclinic.org/diseasesconditions/psoriasis/basics/definition/con-20030838. accessed 15 september 2017. 3. rachakonda td, schupp cw, armstrong aw. psoriasis prevalence among adults in the united states. j am acad dermatol 2014;70(3):512-516. 4. lebwohl m. future psoriasis therapy. dermatologic clinics 1995;13(4):915. 5. bhosle mj, kulkarni a, feldman sr, balkrishnan r. quality of life in patients with psoriasis. health qual life outcomes 2006;4(1):35. colby evans,1 louise humphrey,2 corey pelletier,3 stacie hudgens4 1evans dermatology, austin, tx, us; 2clinical outcomes solutions, folkestone, kent, uk; 3celgene corporation, summit, nj, us; 4clinical outcomes solutions, tucson, az, us group concept mapping to understand the patient perspective and burden of psoriasis conclusions references acknowledgements the authors acknowledge the financial support for this study from celgene corporation. the authors received editorial assistance and printing support from clinical outcomes solutions, sponsored by celgene corporation. presented at the 2017 fall clinical dermatology conference, 12–15 october 2017, las vegas, nevada, us results disclosures ● colby evans is a consultant/speaker for celgene and abbvie; and speaker for novartis. ● louise humphrey and stacie hudgens have nothing to disclose. ● corey pelletier is a celgene employee. • psoriasis is one of the most prevalent autoimmune diseases in the united states and impacts up to 2% of the nation’s population.1 • it is a chronic, symptomatic condition that goes through cycles of weekto month-long flares. some common symptoms of psoriasis are skin redness, burning, itching, and joint stiffness.2 • psoriasis can present at any age, but has been observed to have a bimodal onset across populations, peaking at 15–20 and 55–60 years of age.1 • caucasians have the highest prevalence of psoriasis in the united states at an estimated 3.6%, followed by african americans (1.9%,) hispanics (1.6%,) and others (1.4%).3 • topical corticosteroids are the traditional and most widely used psoriasis therapy in the us, ranging from over-thecounter 1% hydrocortisone to more potent class 1 corticosteroids.4 – additional treatments are phototherapy, systemic retinoids, methotrexate, cyclosporine, apremilast, and newer biological agents.5 • the symptoms and treatment of psoriasis have a significant negative impact on patient-reported quality of life (qol). – a survey by the national psoriasis foundation showed that nearly 75% of patients believed psoriasis had a moderate to large negative impact on their qol, with alterations in their daily activities.5 • there are a number of clinical outcome assessments that have been used to measure qol in psoriasis patients ranging from psoriasis-specific measures (psoriasis index of quality of life, psoriasis disability index), to skin-specific measures (questionnaire on experience with skin complaints, dermatology life quality index) to generic measures (short form-36, euroqol 5d, work productivity assessment index).5 • with a high prevalence and large burden of disease, there is interest to explore and understand patient priorities and unmet needs for the treatment of psoriasis. – this initiative will engage patients, clinicians, and payers to develop research questions and execute prospective research activities with the aim of generating evidence to support identified areas of unmet need in psoriasis. • to collect quantitative and qualitative insights into patients’ experiences with psoriasis that identify the most important and relevant outcomes for psoriasis patients and identify populations of psoriasis patients who may benefit from new treatment options. • group concept mapping (gcm) will be used to develop research questions based on data gathered from patient and clinician participants. guided by these gcm results, data from multiple sources will be collected and triangulated: – patient-reported outcomes (pro) data; – clinical chart data and clinician-reported outcomes data; – qualitative data generated from interviews with psoriasis patients. study design • the study consists of two phases (figure 1): 1. a gcm exercise involving psoriasis patients and clinician participants to identify key concepts and areas of unmet need in the psoriasis patient population. 2. a cross-sectional, non-interventional, mixed-methods study to more thoroughly explore the identified concepts through the administration of surveys and qualitative interviews to psoriasis patients. • this study is currently in progress. • this ongoing study uses a novel methodology to characterize the burden of psoriasis from the patient and clinician perspectives. recruitment • up to 10 sites will be recruited in the united states (us) to identify 120 patients with psoriasis to participate in either the gcm exercise or observational study. • additionally, 10 clinicians will be recruited for the gcm exercise. participant selection criteria patient inclusion criteria • aged ≥ 18 years; • able to read, comprehend, and complete questionnaires and interview in english; • has access to an internet-connected computer/ tablet/ smart-phone; • has clinician-confirmed diagnosis of current moderatesevere psoriasis as judged by clinician in the case report form; and • able to read, comprehend, and sign informed consent. patient exclusion criteria • has a mental or physical condition that would prevent completion of questionnaires or participation in interviews; • is currently enrolled in any other psoriasis interventional study or quality of life (qol) study (registry studies and post-marketing safety studies are permitted); or • has a documented history in the past 12 months of alcohol or other substance abuse. clinician inclusion criteria • is currently practicing as a prescribing dermatologist; • has a significant number of patients treated in their clinical practice with psoriasis; and • is fluent in us english and able to read, comprehend, and sign an informed consent form for participation. clinician exclusion criteria • is on the fda debarment list; or • is unwilling or unable to comply with requirements of the study. background information and chart review • for psoriasis patients, clinicians complete chart data relating to the patient’s disease and treatment history. • clinicians will provide information regarding their work and experience with psoriasis patients (table 1). figure 2. process for conducting gcm study recruitment/ screening via centralized recruitment agency participants sent link and login id for globalmax website concept generation participants respond to prompts sorting participants sort responses into groups based on meaningfulness to them participants sent 2nd link to globalmax website researchers harmonize list of generated concepts rating responses rated by participants using most meaningful/appropriate scale mapping multivariate and cluster analyses to generate 2d concept map of most important treatment outcomes for patients and clinicians figure 1. study schematic clinro = clinician reported outcome; gcm = group concept mapping; pro = patient reported outcome site identification and phase 1 clinician/patient recruitment phase 1 phase 2 gcm exercise identification of key concepts and unmet need patient recruitment and retrospective chart review patient can be identified for the study and consented pro measures data collection chart review and clinro collection conduct patient interviews crf = case report form; gcm = group concept mapping psoriasis patient interviews • twenty psoriasis patients who completed the survey will be scheduled for a qualitative telephone interview with a trained interviewer. • interview content will be guided by the research questions and concepts elicited in the gcm exercise, but is expected to entail: – burden of illness in terms of symptoms, impact experience, functional status, cost of care, and qol; – unmet clinical needs in terms of treatment options; impression of treatment satisfaction. analyses • the results of the gcm exercise will be developed into a visual representation of the burden and unmet needs of psoriasis patients and will be used to develop and select research questions, survey instruments, and interview guides for the observational study. • clinical data and clinician-reported data will be considered against the patient reported qol, symptom, and treatment satisfaction data to measure and characterize the unmet needs and burden of psoriasis from the gcm exercise and to identify populations of psoriasis patients who may benefit from new psoriasis treatments. introduction objective methods table 2. gcm prompts population prompt psoriasis patients • an ideal treatment to manage the symptoms of my psoriasis should … clinicians • an ideal treatment to manage the symptoms of psoriasis should … fc17postercelgeneevansgroupconceptmapping.pdf skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 421 brief articles unilateral pemetrexed-induced pseudocellulitis mimicking bacterial cellulitis fatema s. esaa ba1, skylar n. travis md2, glynis a. scott md2, and christopher t. richardson md, phd2 1university of rochester school of medicine and dentistry, rochester, new york 2department of dermatology, university of rochester medical center, rochester, new york pemetrexed is a multi-targeted anti-folate chemotherapeutic agent approved for the treatment of malignant pleural mesothelioma and locally advanced or metastatic non-small cell lung cancer (nsclc).1 it interferes with dna synthesis by inhibiting thymidylate synthetase and other enzymes involved in folate metabolism.2 it is used as either a single agent or in combination with cisplatin or carboplatin.2 a variety of cutaneous adverse reactions (cars) have been reported with usage of pemetrexed and combinations of pemetrexed and cisplatin/carboplatin. the most common cars, including periorbital edema with conjunctivitis and limb edema with severe fluid retention, have been observed in approximately one-third of patients, but have not significantly influenced treatment.3 cases of more severe cars have also been reported including toxic epidermal necrolysis, asteatotic eczema, radiation recall dermatitis, pityriasis lichenoides, acute generalized exanthematous pustulosis and pseudocellulitis, which typically manifests bilaterally.2, 4-9 here we present a case of unilateral pemetrexed-induced pseudocellulitis. a 67-year-old obese man with a history of peripheral vascular disease and stage iv moderately differentiated adenocarcinoma of the right lung with presumed bone pseudocellulitis, manifesting as erythema, warmth, and tenderness of the lower extremities, is a recently recognized cutaneous adverse reaction (car) associated with the use of pemetrexed, a multi-targeted folate antagonist. this reaction typically manifests bilaterally, helping to distinguish pemetrexed-induced pseudocellulitis from a bacterial cellulitis. we present a case of unilateral pemetrexed-induced pseudocellulitis. the patient was initially treated for cellulitis but failed to respond adequately to antibiotics, prompting a biopsy that showed the characteristic findings of pemetrexed-induced pseudocellulitis. pemetrexedinduced pseudocellulitis is important to recognize as it may be dose-limiting or necessitate treatment modification. furthermore, increased awareness of this car can help clinicians avoid unnecessary antibiotic use. abstract introduction case report skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 422 metastases received four cycles of combination carboplatin and pemetrexed and two maintenance doses of pemetrexed. eight days into his first dose of maintenance pemetrexed, he was admitted to the hospital with fever, pancytopenia and presumed pneumonia. he was initially treated with cefepime and then transitioned to amoxicillinclavulanate, completing a seven-day course of antibiotics. during this admission, he developed erythema of the right lower extremity. ultrasound was negative for deep vein thrombosis (dvt). the erythema slowly improved during admission, though it did not completely resolve. shortly after discharge, the erythema of his right ankle worsened and was associated with new pain and swelling. his primary care physician prescribed trimethoprimsulfamethoxazole out of concern that persistence of the painful erythema was due to a mrsa infection. at a follow-up appointment one week later, he reported minimal improvement. the following week, he received a second dose of maintenance pemetrexed as scheduled by his oncologist. following the treatment, he noticed progression of the erythema and increased tenderness and edema. he was again admitted to the hospital for cellulitis and treated with broad spectrum antibiotics. the erythema failed to improve despite adequate treatment with broad spectrum antibiotics and the dermatology team was consulted. exam was notable for bright red blanching erythema of the right lower extremity extending from the dorsal foot to the distal knee (figure 1). the entire area was warm and tender to light touch. there was also 2+ edema of the lower extremities bilaterally. however, his overall clinical presentation was inconsistent with a poorlycontrolled, antibiotic-resistant infection as he was generally well-appearing, afebrile and figure 1: the patient was initially diagnosed with cellulitis but, after inadequate response to broad spectrum antibiotics, a biopsy was performed consistent with pemetrexed induced pseudocellulitis. without leukocytosis. doppler ultrasound was negative for dvt. a 4-mm punch biopsy of the right upper thigh was performed to evaluate for cellulitis vs pemetrexed-induced pseudocellulitis. biopsy revealed mild acanthosis of the epidermis and superficial lymphocytic infiltrate with numerous eosinophils, characteristic of pemetrexedinduced pseudocellulitis (figure 2). there was no evidence of cutaneous infection. antibiotics and pemetrexed were discontinued and the patient was started on triamcinolone 0.1% cream applied twice daily. at his initial follow up appointment, there was significant improvement in the redness, swelling and pain. on the right lower extremity, extending from the lower thigh skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 423 distally to the toes, was a blanching, light pink patch that was no longer warm or tender. there was superficial desquamation on the right thigh and shin. twice daily application of triamcinolone 0.1% cream for an additional month was recommended, as well as urea 40% cream as needed. pemetrexed was discontinued by oncology and the rash has since resolved and not reappeared over the last six months. figure 2: pathology was consistent with pemetrexedinduced pseudocellulitis, showing mild acanthosis of the epidermis and a superficial lymphocytic infiltrate (a) with numerous eosinophils (b). in this case, the patient’s presentation of unilateral lower extremity erythema, edema, warmth, and tenderness was consistent with cellulitis and was treated as such after the evaluation by multiple specialists, including hematology and oncology, emergency medicine and infectious disease. however, the patient not only failed to respond adequately to antibiotics, but failed to develop any other signs or symptoms of uncontrolled bacterial cellulitis, clues pointing to an alternate diagnosis. in these situations, histologic evaluation can be particularly helpful. while other adverse events of pemetrexed are often attributed to its cytotoxicity, the eosinophilic infiltrate in pseudocellulitis suggests a hypersensitivity reaction. interestingly, pseudocellulitis has also been reported in patients treated with gemcitabine, another chemotherapeutic agent that interferes with dna synthesis.10,11 recognizing the potential for pemetrexedinduced pseudocellulitis or other drug hypersensitivity reactions to present unilaterally could limit unnecessary use of broad-spectrum antibiotics, and in some cases, including this one, may require adjusting a patient’s cancer treatment regimen. conflict of interest disclosures: none. funding: none. corresponding author: christopher t. richardson, md,phd university of rochester medical center 601 elmwood ave, po box 697 rochester, ny 14642 email: crichardson@urmc.rochester.edu discussion a b mailto:christopher_richardsom@urmc.rochester.edu skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 424 references: 1. rollins kd, lindley c. pemetrexed: a multitargeted antifolate. clin ther. 2005 sep;27(9):1343-82. 2. piérard-franchimont c, quatresooz p, reginster m, piérard ge. revisiting cutaneous adverse reactions to pemetrexed. oncology letters. 2011;2(5):769-772. 3. eguia b, ruppert am, fillon j, et al. skin toxicities compromise prolonged pemetrexed treatment. j thorac oncol. 2011 dec;6(12):2083-9 4. then c, von einem jc, müller d et al. toxic epidermal necrolysis after pemetrexed and cisplatin for non-small cell lung cancer in a patient with sharp syndrome. onkologie. 2012;35(12):783-6. 5. vitiello, m, romanelli p, kerdel fa. painful generalized erythematous patches: a severe and unusual cutaneous reaction to pemetrexed. j. am. acad. dermatol. 2011;65(1):243244. 6. frouin e, sebille g, freudenberger s et al. asteatotic eczema ('eczema craquelé') with histopathological interface dermatitis: a new cutaneous reaction following pemetrexed. br j dermatol. 2012 jun;166(6):1359-60 7. santosa a, liau mm, tan kb, tan lc. pemetrexed-induced eccrine squamous syringometaplasia manifesting as pseudocellulitis (in a patient with non– small cell lung cancer). jaad case reports. 2017;3(1):64-66. 8. liau mm, santosa a, huang j, tan lc. pemetrexed-induced lower limb pseudocellulitis. clin exp dermatol. 2017 dec;42(8):914-916. 9. tracey, h. modi b, micheletti rg. pemetrexed-induced pseudocellulitis reaction with eosinophilic infiltrate on skin biopsy. am j dermatopathol. 2017 jan;39(1):e1-e2 10. gill d, schrader j, kelly m et al. gemcitabine associated pseudocellulitis: a missed diagnosis. j oncol pharm pract. 2017 jan 1:1078155217719584. 11. asemota e, reid e, kovarik c. gemcitabine-induced pseudocellulitis in a patient with non–small cell lung carcinoma. jaad case reports. 2015;1(4):178-181. https://www-ncbi-nlm-nih-gov.ezpminer.urmc.rochester.edu/pubmed/?term=rollins%20kd%5bauthor%5d&cauthor=true&cauthor_uid=16291410 https://www-ncbi-nlm-nih-gov.ezpminer.urmc.rochester.edu/pubmed/?term=lindley%20c%5bauthor%5d&cauthor=true&cauthor_uid=16291410 https://www-ncbi-nlm-nih-gov.ezpminer.urmc.rochester.edu/pubmed/?term=eguia%20b%5bauthor%5d&cauthor=true&cauthor_uid=21892100 https://www-ncbi-nlm-nih-gov.ezpminer.urmc.rochester.edu/pubmed/?term=ruppert%20am%5bauthor%5d&cauthor=true&cauthor_uid=21892100 https://www-ncbi-nlm-nih-gov.ezpminer.urmc.rochester.edu/pubmed/?term=fillon%20j%5bauthor%5d&cauthor=true&cauthor_uid=21892100 https://www-ncbi-nlm-nih-gov.ezpminer.urmc.rochester.edu/pubmed/21892100 https://www-ncbi-nlm-nih-gov.ezpminer.urmc.rochester.edu/pubmed/?term=then%20c%5bauthor%5d&cauthor=true&cauthor_uid=23207626 https://www-ncbi-nlm-nih-gov.ezpminer.urmc.rochester.edu/pubmed/?term=von%20einem%20jc%5bauthor%5d&cauthor=true&cauthor_uid=23207626 https://www-ncbi-nlm-nih-gov.ezpminer.urmc.rochester.edu/pubmed/?term=m%c3%bcller%20d%5bauthor%5d&cauthor=true&cauthor_uid=23207626 https://www-ncbi-nlm-nih-gov.ezpminer.urmc.rochester.edu/pubmed/?term=pemetrexed+then+c https://www-ncbi-nlm-nih-gov.ezpminer.urmc.rochester.edu/pubmed/?term=frouin%20e%5bauthor%5d&cauthor=true&cauthor_uid=22182200 https://www-ncbi-nlm-nih-gov.ezpminer.urmc.rochester.edu/pubmed/?term=sebille%20g%5bauthor%5d&cauthor=true&cauthor_uid=22182200 https://www-ncbi-nlm-nih-gov.ezpminer.urmc.rochester.edu/pubmed/?term=freudenberger%20s%5bauthor%5d&cauthor=true&cauthor_uid=22182200 https://www-ncbi-nlm-nih-gov.ezpminer.urmc.rochester.edu/pubmed/22182200 https://www-ncbi-nlm-nih-gov.ezpminer.urmc.rochester.edu/pubmed/22182200 https://www-ncbi-nlm-nih-gov.ezpminer.urmc.rochester.edu/pubmed/?term=liau%20mm%5bauthor%5d&cauthor=true&cauthor_uid=28815694 https://www-ncbi-nlm-nih-gov.ezpminer.urmc.rochester.edu/pubmed/?term=santosa%20a%5bauthor%5d&cauthor=true&cauthor_uid=28815694 https://www-ncbi-nlm-nih-gov.ezpminer.urmc.rochester.edu/pubmed/?term=huang%20j%5bauthor%5d&cauthor=true&cauthor_uid=28815694 https://www-ncbi-nlm-nih-gov.ezpminer.urmc.rochester.edu/pubmed/?term=tan%20lc%5bauthor%5d&cauthor=true&cauthor_uid=28815694 https://www-ncbi-nlm-nih-gov.ezpminer.urmc.rochester.edu/pubmed/28815694 https://www.ncbi.nlm.nih.gov/pubmed/?term=modi%20b%5bauthor%5d&cauthor=true&cauthor_uid=27415636 https://www.ncbi.nlm.nih.gov/pubmed/?term=micheletti%20rg%5bauthor%5d&cauthor=true&cauthor_uid=27415636 https://www.ncbi.nlm.nih.gov/pubmed/27415636 https://www-ncbi-nlm-nih-gov.ezpminer.urmc.rochester.edu/pubmed/?term=gill%20d%5bauthor%5d&cauthor=true&cauthor_uid=28714381 https://www-ncbi-nlm-nih-gov.ezpminer.urmc.rochester.edu/pubmed/?term=schrader%20j%5bauthor%5d&cauthor=true&cauthor_uid=28714381 https://www-ncbi-nlm-nih-gov.ezpminer.urmc.rochester.edu/pubmed/?term=kelly%20m%5bauthor%5d&cauthor=true&cauthor_uid=28714381 https://www-ncbi-nlm-nih-gov.ezpminer.urmc.rochester.edu/pubmed/28714381 https://www-ncbi-nlm-nih-gov.ezpminer.urmc.rochester.edu/pubmed/28714381 tralokinumab 300 mg q2w placebo q2w placebo q2w tralokinumab 300 mg q4w alternating with placebo open-label treatment tralokinumab 300 mg q2w � optional tcs 3:1 randomization washout of tcs and other ad medication 300 mg q2w after initial loading dose (600 mg) patients with clinical response of iga-0/1 or easi-75 2:2:1 randomization screening initial treatment maintenance treatment safety follow-up 66 weeks52 weeks16 weeks0-6 weeks tralokinumab 300 mg q2w placebo q2w ecztra 1 (n=603) ecztra 2 (n=593) ecztra 1 (n=199) ecztra 2 (n=201) figure 1. ecztra 1 and 2 trial design ig a -0 /1 , % n/n 14/197 95/601 16/197 115/601 22/201 131/591 25/201 142/591 sensitivity analysisb (rescue allowed) primary analysisa (nri) primary analysisa (nri) sensitivity analysisb (rescue allowed) ecztra 1 ecztra 240 35 30 25 20 15 10 5 0 placebo tralokinumab 300 mg q2w ea s i75 , % n/n 25/197 150/601 34/197 201/601 23/201 196/591 3/201 224/591 sensitivity analysisb (rescue allowed) primary analysisa (nri) primary analysisa (nri) sensitivity analysisb (rescue allowed) a b 7.1% 8.1% 10.9% 12.4% 15.8%* 19.1%** 22.2%** 24.0%** 12.7% 17.3% 11.4% 16.4% 25.0%*** 33.4%** 33.2%** 37.9%**ecztra 1 ecztra 240 35 30 25 20 15 10 5 0 placebo tralokinumab 300 mg q2w figure 2. iga-0/1 and easi-75 at week 16 ecztra 1a30 25 20 15 10 5 0 a b ecztra 2a week 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 1615 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 1615 week w o rs t d a ily p ru ri tu s n r s re d u ct io n �� 4 , % 30 25 20 15 10 5 0 w o rs t d a ily p ru ri tu s n r s re d u ct io n �� 4 , % placebo (n=194) tralokinumab q2w (n=594) placebo (n=200) tralokinumab q2w (n=575) 20.0% 10.3% 25.0% 9.5% * ** ** *** ** ** *** *** *** *** *** *** ****** ** ** *** *** *** *** *** *** ** *** *** *** ***** figure 3. worst daily pruritus nrs (weekly average) reduction 4introduction results methods objectives ● the objectives of ecztra 1 (nct03131648) and 2 (nct03160885) were to evaluate the efficacy and safety of tralokinumab monotherapy compared with placebo in patients with moderate-to severe ad for up to 1 year, as assessed by severity and extent of ad, itch, and health-related quality of life ecztra 1 (n=802) ecztra 2 (n=794) placebo (n=199) tralokinumab q2w (n=603) placebo (n=201) tralokinumab q2w (n=593) table 1. demographic and clinical characteristics of randomized patients at baseline conclusions ● tralokinumab demonstrated superiority over placebo in all primary and secondary endpoints at week 16 ● the majority of patients maintained responses at week 52 with tralokinumab q2w (without the use of tcs) ● after having achieved response, q4w dosing could be appropriate for some patients ● continued treatment beyond 16 weeks resulted in additional patients achieving treatment success ● the overall frequency of aes among tralokinumab-treated patients was comparable with that in the placebo group over 52 weeks ● specifically targeting il-13 with tralokinumab represents a novel and efficacious approach for the long-term treatment of ad ● atopic dermatitis (ad) is a chronic inflammatory skin disease characterized by intense itch and eczematous lesions1 ● the underlying pathophysiology of ad is a complex and multifaceted combination of skin barrier dysfunction and immune dysregulation, leading to chronic type 2 inflammation2,3 ● tralokinumab is a fully human monoclonal antibody designed to specifically neutralize interleukin (il)-13, a key driver of the underlying inflammation in ad4-8 ● the ecztra 1 and ecztra 2 studies were identically designed, multinational, double-blind, randomized, placebo controlled, 52-week trials of tralokinumab monotherapy in more than 1500 patients with moderate-to-severe ad patients ● eligible patients were 18 years of age, with a confirmed diagnosis of ad for 1 year, and candidates for systemic therapy due to a recent (within 1 year) history of inadequate response to treatment with topical treatments or for whom topical treatments were medically inadvisable ● rescue treatment for ad could be provided if medically necessary. however, patients who received rescue treatment were considered non-responders in the primary analyses study design ● patients were randomly assigned 3:1 to receive either subcutaneous tralokinumab 300 mg or placebo every 2 weeks (q2w) for an initial treatment period of 16 weeks (figure 1) eric simpson,1 andrew blauvelt,2 emma guttman-yassky,3 margitta worm,4 charles lynde,5 hidehisa saeki,6 yves poulin,7 andreas wollenberg8 1department of dermatology, oregon health & science university, portland, or, usa; 2oregon medical research center, portland, or, usa; 3department of dermatology and the immunology institute, icahn school of medicine at mount sinai, new york, ny, usa; 4division of allergy and immunology, department of dermatology, venereology, and allergy, charité – universitätsmedizin berlin, berlin, germany; 5lynde dermatology, probity medical research, markham, on, canada and department of medicine, university of toronto, toronto, on, canada; 6department of dermatology, nippon medical school, tokyo, japan; 7laval university and centre dermatologique du québec métropolitain and centre de recherche dermatologique du québec métropolitain, québec, qc, canada; 8klinikum der universität münchen, klinik und poliklinik für dermatologie und allergologie, munich, germany endpoints ● primary efficacy endpoints were an iga score of 0 (clear) or 1 (almost clear) [iga-0/1] and a 75% improvement in easi (easi-75), both at week 16 ● key secondary endpoints were change from baseline to week 16 in scoring ad (scorad) score, reduction of worst daily pruritus numeric rating scale (nrs) [weekly average] 4 from baseline to week 16, and change from baseline to week 16 in dermatology life quality index (dlqi) score ● maintenance endpoints were iga-0/1 at week 52 among patients with iga-0/1 at week 16, achieved without rescue medication, and easi-75 at week 52 among patients with easi-75 at week 16, achieved without rescue medication, both after initial randomization to tralokinumab ● adverse events (aes) were assessed at baseline and each subsequent visit statistical analysis ● to control for the overall type 1 error rate at a 5% significance level, a prespecified testing hierarchy was used for assessment of the primary, key secondary, and maintenance endpoints ● the primary analysis of the binary endpoints considered patients who received rescue medication (including tcs) and patients with missing data to be non-responders. an alternative analysis was also applied where all observed data was used, irrespective of rescue medication use, with missing data imputed as non-responders — the difference between response rates among treatment groups was analyzed using the cochran-mantel haenszel test, stratified by baseline iga score and region ● for the primary analysis of the continuous endpoints, a repeated measurements model was used, where data collected after permanent discontinuation or initiation of rescue medication were excluded from the analysis ● the primary analysis of the maintenance endpoints considered patients who, prior to week 52, received rescue medication and/or were transferred to open-label treatment as non-responders. the differences in response rates were analyzed using the cochran-mantel-haenszel test, stratified by region patient characteristics ● patients were randomly assigned to recieve either tralokinumab 300 mg every other week or placebo; 603:199 in ecztra 1 and 593:201 in ecztra 2 ● baseline demographics and disease characteristics were well balanced between randomized groups. patients had a long duration of ad and over 50% had severe ad (iga-4) at baseline (table 1) maintenance/open-label phase ● after the initial 16-week treatment period, eligible patients were transferred to either the maintenance phase or open-label tralokinumab as appropriate (figure 1) ● iga-0/1 response at week 16, achieved without rescue medication, was maintained at week 52 in 51.3% and 59.3% of patients who continued tralokinumab q2w (figure 5a) and easi-75 response at week 16, achieved without rescue medication, was maintained at week 52 in 59.6% and 55.8% of patients who continued with tralokinumab q2w (figure 5b) ausa only in ecztra 1; usa and canada in ecztra 2; bfrance, germany, and spain in ecztra 1; italy, poland, russia, denmark, and uk in ecztra 2; cjapan in ecztra 1 and korea in ecztra 2. primary endpoints ● at week 16, significantly greater iga-0/1 and easi-75 response rates were observed with tralokinumab compared with placebo, using both the primary and alternative analysis approaches (figure 2) ● in the primary analysis, iga-0/1 was achieved by 15.8% versus 7.1% (p0.01) and 22.2% versus 10.9% (p0.001) with tralokinumab versus placebo in ecztra 1 and 2 and easi-75 was achieved by 25.0% versus 12.7% and 33.2% versus 11.4% with tralokinumab versus placebo in ecztra 1 and 2 (figure 2) — rescue medication was used by 35.8% and 22.8% of patients receiving tralokinumab and by 46.2% and 44.3% of patients receiving placebo in ecztra 1 and 2, respectively *p<0.01 versus placebo; **p<0.001 versus placebo. ause of rescue medication considered as non-response and missing data imputed as non-response; ball data used as observed at week 16, regardless of rescue medication use, and missing data imputed as non-response. nri, non-responder imputation. primary analysis approach: use of rescue medication considered non-response and missing data imputed as non-response. *p<0.05 versus placebo; **p<0.01 versus placebo; ***p<0.001 versus placebo. abased on full analysis set with baseline worst daily pruritus nrs (weekly average) ≥4. ig a -0 /1 , % n/n n/n ecztra 1 ecztra 270 60 50 40 30 20 10 0 70 60 50 40 30 20 10 0 re-randomization q2w to q2w q2w to q4w q2w to placebo re-randomization q2w to q2w q2w to q4w q2w to placebo ea s i75 , % a b 51.3% 38.9% 47.4% 59.6% 49.1% 33.3% 25.0% 44.9% 21.4% 51.4%* 59.3%** 55.8%** ecztra 1 ecztra 2 28/47 28/57 10/30 43/77 38/74 9/42 20/39 14/36 9/19 32/54 22/49 7/28 figure 5. maintenance of clinical response at week 52a *p<0.01 versus placebo; **p<0.001 versus placebo. aassessed in patients achieving given primary endpoint (iga-0/1, easi-75) at week 16 without use of rescue medication after initial randomization to tralokinumab. patients who, after week 16, received rescue medication or were transferred to open-label treatment are considered non-responders at week 52. missing values imputed as non-response. 7.6% 29.3% 40.7% 53.2% 17.1% 36.5% ig a -0 /1 , % iga-0/160 50 40 30 20 10 0 60 50 40 30 20 10 0 ea s i75 , % a b easi-75 16 20 24 28 32 36 40 44 48 52 week 16 20 24 28 32 36 40 44 48 52 week iga-2 (n=167) iga-3 (n=386) iga-4 (n=132) week 16 iga score 50-�75% (n=269) 25-�50% (n=177) �25% (n=215) week 16 easi reduction figure 6. iga-0/1 and easi-75 with open-label tralokinumab 1 optional tcs by ad disease activity at week 16 data are pooled from ecztra 1 and 2; all patients were initially randomized to tralokinumab up to week 16 n (%) in the initial 16-week period ecztra 1 ecztra 2 placebo (n=196) tralokinumab q2w (n=602) placebo (n=200) tralokinumab q2w (n=592) frequent aes (≥5% in any treatment group)a table 2. summary of aes in the 16 week initial treatment period aaes reported by system organ class and preferred term according to medical dictionary for regulatory activities, version 20.0 in the initial treatment period. references 1. weidinger s, novak n. lancet 2016; 387: 1109–1122. 2. boguniewicz m, leung dy. immunol rev 2011; 242: 233–246. 3. guttman-yassky e et al. semin cutan med surg 2017; 36: 100–103. 4. szegedi k et al. j eur acad dermatol venereol 2015; 29: 2136–2144. 5. popovic b et al. j mol biol 2017; 429: 208–219. 6. furue k et al. immunology 2019; 158: 281–286. 7. tsoi lc et al. j invest dermatol 2019; 139: 1480–1489. 8. bieber t. allergy 2020; 75: 54–62. disclosures eric simpson reports grants and/or personal fees from abbvie, boehringer ingelheim, celgene, dermira, dermavant, forte bio galderma, incyte, kyowa hakko kirin, leo pharma, lilly, medimmune, menlo therapeutics, merck, novartis, ortho dermatologics, pfizer, pierre fabre dermo cosmetique, regeneron, sanofi, tioga, and valeant. andrew blauvelt has served as a scientific adviser and/or clinical study investigator for abbvie, aclaris, almirall, arena, athenex, boehringer ingelheim, bristol-myers squibb, dermavant, dermira, lilly, flx bio, forte, galderma, janssen, leo pharma, novartis, ortho, pfizer, regeneron, sandoz, sanofi genzyme, sun pharma, and ucb pharma, and as a paid speaker for abbvie. emma guttman-yassky has received honoraria for consultant services from abbvie, almirall, amgen, asana biosciences, boerhinger ingelhiem, cara therapeutics, celgene, concert, dbv, dermira, ds biopharma, lilly, emd serono, escalier, galderma, glenmark, kyowa kirin, leo pharma, mitsubishi tanabe, pfizer, rapt therapeutics, regeneron, sanofi, sienna biopharma, and union therapeutics, and received research grants for investigator services from abbvie, almirall, amgen, anaptysbio, asana biosciences, boerhinger ingelhiem, celgene, concert, dermavant, dermira, ds biopharma, lilly, glenmark, galderma, innovaderm, janssen, kiniska, kyowa kirin, leo pharma, novan, pfizer, ralexar, regeneron, sienna biopharma, ucb, and union therapeutics. margitta worm declares that she has receipt honoraria or consultation fees by alk-abelló arzneimittel gmbh, mylan germany gmbh, leo pharma gmbh, sanofi-aventis deutschland gmbh, regeneron pharmaceuticals, inc., dbv technologies s.a, stallergenes gmbh, hal allergie gmbh, allergopharma gmbh & co. kg, bencard allergie gmbh, aimmune therapeutics uk limited, actelion pharmaceuticals deutschland gmbh, novartis ag and biotest ag. charles lynde has received honoraria or consultant fees from abbvie, amgen, bausch health, boerhinger ingelheim, celgene, lilly, galderma, glenmark, janssen, leo pharma, novartis, pfizer, regeneron, sanofi, sun pharma, and valeant. hidehisa saeki is an advisor to leo pharma. yves poulin has received grant funding and honoraria for services as an investigator, speaker, and member of advisory boards from abbvie, amgen, bausch, centocor ortho/janssen, ucb biopharma, and has received grant funding as an investigator from baxter, boehringer ingelheim, bristol-myers squibb, celgene, galderma, genentech, glaxosmithkline, lilly, incyte, leo pharma, medimmune, merck, novartis, pfizer, regeneron, serono, and takeda. andreas wollenberg has received grants, personal fees, or nonfinancial support from abbvie, almirall, beiersdorf, bioderma, chugai, galapagos, galderma, hans karrer, leo pharma, lilly, l’oreal, maruho, medimmune, novartis, pfizer, pierre fabre, regeneron, santen, and sanofi-aventis. the ecztra 1 and 2 studies were sponsored by leo pharma. patient images provided with consent to use; courtesy of prof. ketty peris. figure 4. example patient case of improvement in easi from baseline to week 16 week 0 easi: 32 nrs: 8 week 8 easi: 4 nrs: 3 week 16 easi: 4 nrs: 3 efficacy and safety of tralokinumab monotherapy in adult patients with moderate-to-severe atopic dermatitis: results from two 52-week, phase 3 trials (ecztra 1 and ecztra 2) 2020 fall clinical dermatology conference, october 29-november 1, 2020, live virtual meeting secondary endpoints ● a reduction in worst daily pruritus nrs (weekly average) 4 was achieved by more patients treated with tralokinumab than with placebo in ecztra 1 (20% vs. 10.3%; p=0.002) and in ecztra 2 (25% vs. 9.5%; p0.001) at week 16 (figure 3) ● mean change from baseline in scorad at week 16 was greater with tralokinumab compared with placebo in ecztra 1 (–25.2 vs. –14.7; p0.001) and ecztra 2 (–28.1 vs. –14.0; p0.001) ● mean change from baseline in dlqi at week 16 was greater with tralokinumab than with placebo in ecztra 1 (–7.1 vs. –5.0; p=0.02) and ecztra 2 (–8.8 vs. –4.9; p0.001) ● greater improvements in scorad and dlqi with tralokinumab compared with placebo were observed from the first assessment (week 2) and at each assessment throughout the initial treatment period ● at 16 weeks, tralokinumab responders (investigator’s global assessment [iga]-0/1 and/or eczema area and severity index [easi]-75 were re-randomized 2:2:1 to receive tralokinumab 300mg q2w or every 4 weeks (q4w), or placebo, for an additional 36 weeks of maintenance treatment ● non-responders at week 16 were transferred to open-label tralokinumab 300 mg q2w with optional use of topical corticosteroids (tcs) for an additional 36 weeks ● some patients − transferred to open-label tralokinumab q2w plus optional tcs − not achieving iga-0/1 or easi-75 at week 16 improved with continued treatment (figure 6) safety ● the overall frequency and severity of aes over 16 weeks was comparable between tralokinumab and placebo (table 2) ● in total, 97% of conjunctivitis cases were mild to moderate, and only one led to treatmentdiscontinuation ● the safety profile at week 52 was comparable with that in the initial treatment period ● there was visible improvement in ad lesions within 16 weeks (figure 4) powerpoint presentation figure 1: schematic of study design of pso-insightful, [nct02310646]2 poster presented at the fall clinical dermatology conference in las vegas, nv; october 12-15, 2017. up to 14 days, if needed cal/bd foam cal/bd foam 7 days 7 days visit 2 day 8 visit 1 day 1 screening day -28 to 1 visit 3 day 15 cross-overrandomization 4-week washout, if needed follow-up cal/bd gel cal/bd gel patient preference for calcipotriene 0.005%/betamethasone dipropionate 0.064% foam or topical suspension vs. latest topical treatment in the pso-insightful study jennifer soung, md,1 lisa tiu, pharmd,2 karen veverka, phd,2 chih-ho hong, md3 1southern california dermatology; 2leo pharma inc; 3university of british columbia, department of dermatology and skin science and probity medical research introduction results conclusions materials & methods acknowledgements references  topical therapies are a mainstay in psoriasis vulgaris treatment and are used in combination therapy even in patients receiving systemic or biologic therapy  patient preference for vehicle formulation can impact adherence and, consequently, real-life effectiveness  the pso-insightful study was designed to assess patient-reported factors that influence preference following once-daily topical treatment with calcipotriene 0.005%/betamethasone dipropionate 0.064% (cal/bd) foam and gel1  questionnaires (including topical product usability questionnaire, tpuq; comparison to latest topical treatment, cltt) were completed by patients at baseline and timepoints during the study to assess usability and preference differences pso-insightful study design  pso-insightful was a prospective, multicenter, phase iiib, open-label, randomized, two-arm crossover study including patients ≥18 years with mild-to-severe psoriasis of ≥6 months’ duration involving 2-30% bsa and mpasi of ≥2 (table 1)  after 4-week washout, 213 patients were randomized 1:1 to once-daily cal/bd foam for 1 week, followed by cal/bd gel for 1 week, or vice-versa (figure 1) study assessments  patients completed questionnaires to assess therapy usability and preference differences o topical product usability questionnaire (tpuq) o comparison to latest topical treatment (cltt) all patients n = 212 (%) age category, n (%) 18 – 39 years 48 (22.6) 40 – 59 years 92 (43.4) ≥ 60 years 72 (34.0) male : female, n (%) 133:79 (63:37) bmi, n (%) < 25 kg/m2 37 (17.5) 25 – 30 kg/m2 73 (34.4) > 30 kg/m2 102 (48.1) pga, n (%) mild 61 (28.8) moderate 122 (57.5) severe 29 (13.7) duration of psoriasis, n (%) < 2 years 4 (1.9) 2 – 5 years 30 (14.2) > 5 years 178 (84.0) bsa, n (%) < 4% 93 (43.9) 4 – 6% 56 (26.4) 6 – 11% 38 (17.9) 11 – 15% 11 (5.2) ≥ 15% 14 (6.6) mpasi, n (%) 2 – 5 86 (40.6) 5.1 – 10 91 (42.9) > 10 35 (16.5) mean dlqi 7.8 localized:widespread distribution of psoriasis, % 62:38 table 1. patient demographics and baseline characteristics (adapted from pso-insightful) bmi, body mass index; bsa, body surface area; mpasi, modified psoriasis and severity index; pga, physician’s global assessment of disease severity  full analysis set comprised all randomized patients who completed an on-study questionnaire  ltt analysis set comprised all randomized patients who had used topical treatment within 3 months before baseline statistical analysis topical product usability questionnaire (tpuq)  each patient assessed the extent to which they agreed with each of the 26 items using 5-point scale (-2 to 2), organized into four domains: “application”, “formulation”, “container”, “satisfaction,” regarding product usability.  frequency: o following randomization, the tpuq was used to assess the ltt at baseline o during visits to the clinic at the end of weeks 1 and 2, patients completed tpuq based on their treatment experience during the previous 7 days comparison to latest topical treatment (cltt)  patients stated whether they preferred their ltt or cal/bd foam/gel, or had no preference  frequency: o during visits to the clinic at the end of weeks 1 and 2, patients completed cltt based on their treatment experience during the previous 7 days  overall, patients from the pso-insightful study had stronger preferences for either cal/bd foam or gel as compared to their last topical treatment  these results from the topical product usability questionnaire are further corroborated with the similar results in the comparison to latest topical treatment survey  the significant differences observed in favor of cal/bd foam as compared to the topical suspension formulation are related mainly to application and a “feeling of relief” which may be attributable to the vehicle  these data provide insight into aspects of topical product usability, but more robust research is necessary to obtain a complete understanding ltt (n=118) cal/bd foam (n=116) cal/bd topical suspension (n=115) application domain scores ease of application 1.4 1.2 1.5 ease of application on lesion only 1.3 0.9* 1.4 ease of spreading 1.5 1.5 1.7* lack of mess 0.6 0.9 1.0** good for use on small areas 1.1 1.0 1.4* good for use on large areas 0.9 1.4*** 1.5*** quick to apply 1.2 1.5** 1.3 total time spent acceptable 1.1 1.6*** 1.4** easily incorporated into daily routine 1.0 1.5*** 1.4*** formulation domain scores quickly absorbed 0.2 0.7** 0.6** dried quickly 0 0.5** 0.4** immediate feeling of relief 0.1 1.1*** 0.7*** felt soothing 0.6 1.3*** 1.0** appealing to touch 0.2 1.0*** 0.9*** felt moisturizing 0.6 1.3*** 1.2*** not greasy –0.5 0.2*** 0.2*** odourless 1.2 1.3 1.5** no staining 0.4 0.9** 0.9*** container domain scores easy to get medication out of container 1.3 1.2 1.3 easy to use 1.3 1.2 1.4 easy to keep clean 1.1 1.3 1.3 accurately dispense wanted amount 1.0 0.9 1.5*** satisfaction domain scores confidence in using 0.6 1.3*** 1.2*** would use regularly 0.9 1.4** 1.3* would recommend 0.4 1.3*** 1.0*** overall satisfaction 0.3 1.2*** 1.1*** table 2. mean tpuq scores compared with llt, by domain, for cal/bd foam and topical suspension range: –2, strongly disagree to +2, strongly agree *p<0.05; **p<0.01; ***p<0.001 vs ltt. ltt included various corticosteroids (of different potencies) and combination products, with similar types of products in all categories (ointment, cream, ‘other’) cal/bd foam or cal/bd topical suspension vs. ltt:  mean tpuq domain scores were often significantly in favor of both cal/bd foam and topical suspension compared with ltt  scores for cal/bd topical suspension were generally higher than for ltt  most scores for cal/bd foam were higher, although some related to ease of application and container items were comparable to ltt cal/bd foam vs. cal/bd topical suspension:  mean application, container and satisfaction domain scores were high for both cal/bd foam and gel  both cal/bd foam and cal/bd gel had very high application domain scores for: o good for use on large areas o total time spent acceptable o quick to apply o easily incorporated into daily routine  significant differences observed in favor of cal/bd foam vs topical suspension in the domains of “immediate feeling of relief” and “soothing feeling”  significant differences observed in favor of cal/bd topical suspension vs foam included: o ease of application, ease of application on lesion only, and ease of spreading o good for use on small areas o odorless o accurately dispensed wanted amount cal/bd foam (n=212) cal/bd topical suspension (n=212) p value application domain scores ease of application 1.1 1.5 ** ease of application on lesion only 0.9 1.4 *** ease of spreading 1.5 1.7 ** lack of mess 0.8 1.0 ns good for use on small areas 1.0 1.4 *** good for use on large areas 1.4 1.5 ns quick to apply 1.4 1.4 ns total time spent acceptable 1.5 1.5 ns easily incorporated into daily routine 1.4 1.5 ns formulation domain scores quickly absorbed 0.7 0.7 ns dried quickly 0.5 0.5 ns immediate feeling of relief 1.0 0.7 ** felt soothing 1.2 1.0 ** appealing to touch 0.9 0.9 ns felt moisturizing 1.1 1.2 ns not greasy 0 0.3 * odourless 1.3 1.6 *** no staining 1.0 1.0 ns container domain scores easy to get medication out of container 1.1 1.3 ns easy to use 1.1 1.4 *** easy to keep clean 1.2 1.4 * accurately dispense wanted amount 0.9 1.5 *** satisfaction domain scores confidence in using 1.2 1.2 ns would use regularly 1.3 1.3 ns would recommend 1.2 1.1 ns overall satisfaction 1.1 1.2 ns range: –2, strongly disagree to +2, strongly agree *p<0.05; **p<0.01; ***p<0.001 table 3. mean tpuq scores, by domain, for cal/bd foam and topical suspension all patients; foam-gel* localized (n = 128) 0.5 ± 8.8 widespread (n = 78) -2.1 ± 8.2 all patients (n = 204) -0.5 ± 8.2 *negative difference indicates preference for gel table 4. difference in total formulation score (tpuq) between study treatments by psoriasis distribution phenotype (fas) differences in tpuq scores between study treatments by psoriasis distribution  the forward selection procedure identified psoriasis distribution as a significant factor  trend towards more favorable scores for cal/bd foam in patients with localized distribution and in favor of gel for patients with widespread distribution 1 hong c-h, papp ka, lophaven kw, et al. patients with psoriasis have different preferences for topical therapy, highlighting the importance of individualized treatment approaches: randomized phase iiib pso-insightful study [submitted]. 2 clinicaltrials.gov. bethesda (md): national library of medicine (us). 2017 jun 1. identifier: nct02310646. patient insights following use of leo 90100 aerosol foam and daivobet® gel in subjects with psoriasis vulgaris. https://clinicaltrials.gov/ct2/show/nct02310646?term=nct02310646&rank=1 this study was sponsored by leo pharma; editorial support was provided by dharm patel, phd at leo pharma inc. us. slide number 1 post hoc analysis of health-related quality of life in the same patient population is presented in the poster titled “health-related quality of life (hrql) in patients with advanced cutaneous squamous cell carcinoma (cscc) treated with cemiplimab: post hoc exploratory analysis of a phase 2 clinical trial”, also available on the 2020 fall clinical dermatology conference platform. references 1. que skt et al. j am acad dermatol. 2018;78:237–247. 2. cranmer ld et al. oncologist. 2010;15:1320–1328. 3. national comprehensive cancer network. nccn clinical practice guidelines in oncology: squamous cell skin cancer (version 2.2019). 2018. available at: https://www.nccn.org/professionals/physician_gls/pdf/squamous.pdf. [accessed march 20, 2020]. 4. karia ps et al. j clin oncol. 2014;32:327–334. 5. weinberg as et al. dermatol surg. 2007;33:885–899. 6. schmults cd et al. jama dermatol. 2013;149:541–547. 7. cowey c et al. cancer med. 2020 [in press]. 8. burova e et al. mol cancer ther. 2017;16:861–870. 9. migden mr et al. lancet oncol. 2020;21:294–305. 10. migden mr et al. n engl j med. 2018;379:341–351. 11. rischin d et al. poster presented at maui dermatology conference, january 25–29, 2020. 12. eisenhauer ea et al. eur j cancer. 2009;45:228–247. acknowledgments the authors would like to thank the patients, their families, all other investigators, and all investigational site members involved in this study. the study was funded by regeneron pharmaceuticals, inc. and sanofi. medical writing support and typesetting was provided by kate carolan, phd, of prime, knutsford, uk, funded by regeneron pharmaceuticals, inc. and sanofi. for any questions or comments, please contact dr danny rischin, danny.rischin@petermac.org disclosures danny rischin reports institutional research grant and funding from regeneron pharmaceuticals, inc., roche, merck sharp & dohme, bristol-myers squibb, and glaxosmithkline; uncompensated scientific committee and advisory board from merck sharp & dohme, regeneron pharmaceuticals, inc., sanofi, glaxosmithkline, and bristol-myers squibb; travel and accommodation from merck sharp & dohme and glaxosmithkline. nikhil i. khushalani reports grants from regeneron pharmaceuticals, inc.; grants and advisory board fees from bristol-myers squibb and huya bioscience international; advisory board fees from emd serono, regeneron pharmaceuticals, inc., genentech, astrazeneca (data safety monitoring committee), merck, array biopharma, jounce therapeutics, and immunocore; grants from merck, novartis, glaxosmithkline, cellgene, and amgen; honorarium from sanofi; and common stock ownership of bellicum pharmaceuticals, mazor robotics, amarin, and transenetrix. chrysalyne d. schmults reports steering committee member for castle biosciences; a steering committee member and consultant for regeneron pharmaceuticals, inc.; a consultant for sanofi; research funding from castle biosciences, regeneron pharmaceuticals, inc., novartis, genentech, and merck, and is a chair for the national comprehensive cancer network. alexander guminski reports personal fees and non-financial support (advisory board and travel support) from bristol-myers squibb and sun pharma; personal fees (advisory board) from merck kgaa, eisai, and pfizer; non-financial (travel) support from astellas; and clinical trial unit support from ppd australia. anne lynn s. chang reports consulting and advisory roles at regeneron pharmaceuticals, inc. and merck; research funding from regeneron pharmaceuticals, inc., novartis, galderma, and merck. karl d. lewis reports grants and personal fees from regeneron pharmaceuticals, inc. during the conduct of the study. annette m. lim reports uncompensated advisory board from merck sharp & dohme and bristol-myers squibb with travel and accommodation expenses. leonel hernandez-aya reports consulting and advisory roles at massive bio; speakers’ bureau roles at sanofi and regeneron pharmaceuticals, inc.; travel, accommodations, and expenses from regeneron pharmaceuticals, inc., sanofi, and bristol-myers squibb; research funding from bristol-myers squibb, regeneron pharmaceuticals, inc., immunocore, merck sharp & dohme, polynoma, corvus pharmaceuticals, roche, merck serono, amgen, medimmune, and takeda. brett g.m. hughes reports consulting or advisory roles at merck sharp & dohme, bristol myers squibb, astrazeneca, pfizer, roche, eisai, and merck; institutional research funding from amgen. dirk schadendorf reports institutional patients’ fees from regeneron pharmaceuticals, inc.; advisory board honorarium fees from amgen and leo pharma; speaker fee from boehringer ingelheim; advisory board, speaker honorarium and patients’ fees from roche, novartis, bristol-myers squibb, and merck-emd; advisory board and speaker honorarium fees from incyte and pierre fabre; advisory board honorarium and patients’ fees from msd, steering committee honorarium fees from 4sc, advisory board fees from astrazeneca, pfizer, and array; advisory board and patients’ fees from philiogen. axel hauschild reports institutional grants, speaker’s honoraria, and consultancy fees from amgen, bristol-myers squibb, merck sharp & dohme/merck, pierre fabre, provectus, roche, and novartis; institutional grants and consultancy fees from merck serono, philogen, and regeneron pharmaceuticals, inc.; consultancy fees from oncosec. michael r. migden reports honoraria and travel expenses from regeneron pharmaceuticals, inc., sanofi, novartis, genentech, eli lilly, and sun pharma; institutional research funding from regeneron pharmaceuticals, inc., novartis, genentech, and eli lilly. elizabeth stankevich, jocelyn booth, siyu li, zhen chen, emmanuel okoye, israel lowy, and matthew g. fury are employees and shareholders of regeneron pharmaceuticals, inc. summary and conclusion • for patients with advanced cscc, cemiplimab achieved orr of 46.1%. • patients had deepening responses over time as evidenced by increasing complete response rates.9–11 overall, the complete response rate is now 16.1% and median time to complete response was 11.2 months. • dor and os are longer than what has been previously described with other agents.7 • with median dor not reached after an additional 1 year of follow-up, this analysis indicates an increasing, clinically meaningful dor with cemiplimab. • the discontinuation rate, regardless of attribution, was low and most traes were grades 1–2. synopsis • cutaneous squamous cell carcinoma (cscc) is the second most common cancer in the us and its incidence is increasing.1 • most cases of cscc are cured by complete surgical excision.2,3 however, a small but substantial number of patients present with either metastatic cscc (mcscc) or locally advanced cscc (lacscc) not amenable to curative surgery or curative radiotherapy (collectively referred to as “advanced cscc”), both of which have poor prognoses.4–6 • historical data shows median overall survival (os) of approximately 15 months with conventional chemotherapy or epidermal growth factor receptor inhibitors.7 • cemiplimab is a high-affinity, highly potent human immunoglobulin g4 monoclonal antibody to the programmed cell death (pd)-1 receptor.8 • cemiplimab monotherapy achieved clinically meaningful activity in patients with advanced cscc and has a safety profile consistent with other anti–pd-1 agents.9–11 • based on initial data (median follow-up of 9.4 months in the pivotal study, nct02760498), cemiplimab (cemiplimab-rwlc in the us) was approved for the treatment of patients with advanced cscc. group 1 – adult patients with metastatic (nodal and/or distant) cscc cemiplimab 3 mg/kg q2w iv, for up to 96 weeks cemiplimab 350 mg q3w iv, for up to 54 weeks tumor response assessment by icr (recist 1.1 for scans; modified who criteria for photos) tumor imaging every 8 weeks for the assessment of clinical activity tumor imaging every 9 weeks for the assessment of clinical activity group 3 – adult patients with metastatic (nodal and/or distant) cscc group 2 – lacscc key inclusion criteria • ecog performance status of 0 or 1 • adequate organ function • groups 1 and 3: at least one lesion measurable by recist 1.1 • group 2 at least one lesion measurable by digital medical photography cscc lesion that is not amenable to curative surgery or curative radiation therapy per investigators’ assessment tumor biopsies at baseline and on day 29, for exploratory biomarker analysis, unless considered to have unacceptable safety risks by the investigator key exclusion criteria • ongoing or recent (within 5 years) autoimmune disease requiring systemic immunosuppression • prior treatments with anti–pd-1 or anti–pd-l1 therapy • history of solid organ transplant, concurrent malignancies (unless indolent or not considered life-threatening; for example, basal cell carcinoma), or hematologic malignancies figure 1. study design ecog, eastern cooperative oncology group; iv, intravenously; pd-l1, pd-ligand 1. phase 2 study of cemiplimab in patients with advanced cutaneous squamous cell carcinoma (cscc): longer follow-up danny rischin,1 nikhil i. khushalani,2 chrysalyne d. schmults,3 alexander guminski,4 anne lynn s. chang,5 karl d. lewis,6 annette m. lim,1 leonel hernandez-aya,7 brett g.m. hughes,8 dirk schadendorf,9 axel hauschild,10 elizabeth stankevich,11 jocelyn booth,11 suk-young yoo,11 zhen chen,12 emmanuel okoye,13 israel lowy,12 matthew g. fury,12 michael r. migden14 1department of medical oncology, peter maccallum cancer centre, melbourne, australia; 2department of cutaneous oncology, moffitt cancer center, tampa, fl, usa; 3department of dermatology, brigham and women’s hospital, harvard medical school, boston, ma, usa; 4department of medical oncology, royal north shore hospital, st leonards, australia; 5department of dermatology, stanford university school of medicine, redwood city, ca, usa; 6university of colorado denver, school of medicine, aurora, co, usa; 7division of medical oncology, department of medicine, washington university school of medicine, st louis, mo, usa; 8royal brisbane & women’s hospital and university of queensland, brisbane, australia; 9university hospital essen, essen and german cancer consortium, essen, germany; 10schleswig-holstein university hospital, kiel, germany; 11regeneron pharmaceuticals, inc., basking ridge, nj, usa; 12regeneron pharmaceuticals, inc., tarrytown, ny, usa; 13regeneron pharmaceuticals, inc., london, uk; 14departments of dermatology and head and neck surgery, university of texas md anderson cancer center, houston, tx, usa results patients • a total of 193 patients were enrolled (group 1, n=59; group 2, n=78; group 3, n=56) (table 1). table 1. baseline demographics advanced cscc (n=193) median age, years (range) 72.0 (38–96) male, n (%) 161 (83.4) ecog performance status, n (%) 0 86 (44.6) 1 107 (55.4) primary cscc site: head and neck, n (%) 131 (67.9) mcscc, n (%) 115 (59.6) lacscc, n (%) 78 (40.4) patients with cemiplimab as first-line therapy, n (%) 128 (66.3) patients with prior systemic therapy, n (%)† 65 (33.7) median duration of exposure to cemiplimab, weeks (range) 51.1 (2.0–109.3) median number of doses of cemiplimab administered (range) 18.0 (1–48) †settings for prior lines of therapy included metastatic disease, adjuvant, chemotherapy with concurrent radiation, or other and the most common types of prior systemic therapy were platinum compounds (n=46/65 [70.8%]) and monoclonal antibodies (n=18/65 [27.7%]). table 2. duration of follow-up and tumor response to cemiplimab per icr group 1 (mcscc) 3 mg/kg q2w (n=59) group 2 (lacscc) 3 mg/kg q2w (n=78) group 3 (mcscc) 350 mg q3w (n=56) total (n=193) median duration of follow-up, months (range) 18.5 (1.1–36.1) 15.5 (0.8–35.6) 17.3 (0.6–26.3) 15.7 (0.6–36.1) orr, % (95% ci) 50.8 (37.5–64.1) 44.9 (33.6–56.6) 42.9 (29.7–56.8) 46.1 (38.9–53.4) complete response, n (%) 12 (20.3) 10 (12.8) 9 (16.1) 31 (16.1) partial response, n (%) 18 (30.5) 25 (32.1) 15 (26.8) 58 (30.1) stable disease, n (%) 9 (15.3) 27 (34.6) 10 (17.9) 46 (23.8) non-complete response/non-progressive disease, n (%) 3 (5.1) 0 2 (3.6) 5 (2.6) progressive disease, n (%) 10 (16.9) 10 (12.8) 14 (25.0) 34 (17.6) not evaluable, n (%) 7 (11.9) 6 (7.7) 6 (10.7) 19 (9.8) disease control rate, % (95% ci) 71.2 (57.9–82.2) 79.5 (68.8–87.8) 64.3 (50.4–76.6) 72.5 (65.7–78.7) durable disease control rate,† % (95% ci) 61.0 (47.4–73.5) 62.8 (51.1–73.5) 57.1 (43.2–70.3) 60.6 (53.3–67.6) median observed time to response, months (iqr)‡ 1.9 (1.8–2.0) 2.1 (1.9–3.8) 2.1 (2.1–4.2) 2.1 (1.9–3.7) median observed time to complete response, months (iqr) 11.1 (7.5–18.4) 10.5 (7.4–12.9) 12.4 (8.2–16.6) 11.2 (7.4–14.8) median dor, months (95% ci)‡ nr (20.7–ne) nr (18.4–ne) nr (ne–ne) nr (28.8–ne) kaplan–meier 12-month estimate of patients with ongoing response, % (95% ci) 89.5 (70.9–96.5) 83.2 (64.1–92.7) 91.7 (70.6–97.8) 87.8 (78.5–93.3) kaplan–meier 24-month estimate of patients with ongoing response, % (95% ci) 68.8 (46.9–83.2) 62.5 (38.4–79.4) ne (ne, ne) 69.4 (55.6–79.6) †defined as the proportion of patients without progressive disease for at least 105 days. ‡based on number of patients with confirmed complete or partial response. orr per inv was 54.4% (95% ci: 47.1–61.6) for all patients; 50.8% (95% ci: 37.5–64.1) for group 1, 56.4% (95% ci: 44.7–67.6) for group 2, and 55.4% (95% ci: 41.5–68.7) for group 3. orr per inv was 57.8% (95% ci: 48.8–66.5) among treatment-naïve patients and 47.7% (95% ci: 35.1–60.5) among previously treated patients. ci, confidence interval; ne, not evaluable; nr, not reached. table 3. teaes regardless of attribution advanced cscc (n=193) n (%) any grade grade ≥3 any 192 (99.5) 94 (48.7) led to discontinuation 19 (9.8) 14 (7.3) most common† fatigue 67 (34.7) 5 (2.6) diarrhea 53 (27.5) 2 (1.0) nausea 46 (23.8) 0 pruritus 41 (21.2) 0 rash 32 (16.6) 1 (0.5) cough 32 (16.6) 0 arthralgia 28 (14.5) 1 (0.5) constipation 26 (13.5) 1 (0.5) vomiting 24 (12.4) 1 (0.5) actinic keratosis 23 (11.9) 0 maculopapular rash 23 (11.9) 1 (0.5) anemia 22 (11.4) 8 (4.1) hypothyroidism 22 (11.4) 0 headache 21 (10.9) 0 upper respiratory tract infection 20 (10.4) 0 †teaes reported in ≥10% of patients, ordered by frequency of any grade. • orr per icr was 46.1% (95% ci: 38.9–53.4) among all patients; 50.8% (95% ci: 37.5–64.1) for group 1, 44.9% (95% ci: 33.6–56.6) for group 2, and 42.9% (95% ci: 29.7–56.8) for group 3 (table 2). • per icr, orr was 48.4% and 41.5% among those who had not received prior anticancer systemic therapy (n=128) and those who had received prior anticancer systemic therapy (n=65), respectively. • overall, the observed time to response was 2 months for 41 (46.1%) patients, 2–4 months for 29 (32.6%) patients, 4–6 months for eight (9.0%) patients, and >6 months for 11 (12.4%) patients. • median dor has not been reached (observed dor range: 1.9–34.3 months). in responding patients, the estimated proportion of patients with ongoing response at 24 months was 69.4% (95% ci: 55.6–79.6) (figure 3). treatment-emergent adverse events • in total, 192 (99.5%) patients experienced at least one teae of any grade regardless of attribution (table 3). • overall, the most common teaes of any grade were fatigue (n=67, 34.7%), diarrhea (n=53, 27.5%), and nausea (n=46, 23.8%). • grade ≥3 teaes regardless of attribution occurred in 94 (48.7%) of patients. the most common grade ≥3 teaes were hypertension (n=9; 4.7%) and anemia and cellulitis (each n=8; 4.1%). • grade ≥3 treatment-related adverse events (traes) were reported in 33 (17.1%) patients, with the most common being pneumonitis (n=5, 2.6%), autoimmune hepatitis (n=3; 1.6%), anemia, colitis, and diarrhea (all n=2; 1.0%). • no new teaes resulting in death were reported compared to previous reports.9–11 clinical activity • complete response rates at primary analysis, ~1-year follow-up for groups 1, 2, and 3, and ~2-year follow-up for group 1 are shown in figure 2. • among 89 responders, median time to complete response was 11.2 months (interquartile range [iqr], 7.4–14.8). • estimated median pfs was 18.4 months (95% ci: 10.3–24.3) for all patients. the kaplan–meier estimated progression-free probability at 24 months was 44.2% (95% ci: 36.1–52.1) (figure 4a). • median os has not been reached. the kaplan–meier estimated probability of os at 24 months was 73.3% (95% ci: 66.1–79.2) (figure 4b). figure 3. kaplan–meier curves of dor per icr 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 p ro b a b ili ty o f n o p ro g re s s io n o r d e a th month number of patients at risk 30 30 29 28 23 23 23 23 23 20 18 16 16 16 10 9 6 2 0 0 0group 1 (n=59) 35 33 32 30 27 25 22 21 17 14 10 8 6 6 5 4 0 0 0 0 0group 2 (n=78) 24 24 24 23 21 21 20 19 17 11 5 0 0 0 0 0 0 0 0 0 0group 3 (n=56) total (n=193) 89 87 85 81 71 69 65 63 57 45 33 24 22 22 15 13 6 2 0 0 0 group 1 (mcscc) 3 mg/kg q2w (n=59) group 2 (lacscc) 3 mg/kg q2w (n=78) group 3 (mcscc) 350 mg q3w (n=56) total (n=193) figure 2. complete response rates per icr 25 20 15 10 5 0 c o m p le te r e s p o n s e r a te s ( % ) group 1 (mcscc) 3 mg/kg q2w group 2 (lacscc)† 3 mg/kg q2w group 3 (mcscc) 350 mg q3w n=10 12.8 n=3 5.4 n=4 6.8 n=10 16.9 n=12 20.3 n=10 12.8 n=9 16.1 primary ~1-year follow-up ~2-year follow-up figure 4. kaplan–meier curves for a) pfs per icr and b) os group 1 (mcscc) 3 mg/kg q2w (n=59) group 2 (lacscc) 3 mg/kg q2w (n=78) group 3 (mcscc) 350 mg q3w (n=56) total (n=193) 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 p ro b a b ili ty o f o s monthnumber of patients at risk 59 56 52 49 47 46 41 39 39 38 38 37 35 33 24 16 11 4 1 0group 1 (n=59) 47 78 76 73 67 65 64 62 59 54 44 41 33 25 22 15 12 8 3 1 0group 2 (n=78) 65 56 52 49 46 45 38 38 38 37 29 20 9 2 0 0 0 0 0 0 0group 3 (n=56) 44 total (n=193) 193 184 174 162 157 156 148 141 136 130 111 99 79 62 55 39 28 19 7 2 0 b group 1 (mcscc) 3 mg/kg q2w (n=59) group 2 (lacscc) 3 mg/kg q2w (n=78) group 3 (mcscc) 350 mg q3w (n=56) total (n=193) 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 p ro b a b ili ty o f p f s month number of patients at risk 59 42 38 36 32 27 27 27 27 27 24 24 21 20 20 12 9 6 1 0 0group 1 (n=59) 78 61 48 43 39 37 33 29 26 20 17 16 12 10 7 5 5 2 0 0 0group 2 (n=78) 56 48 33 31 31 28 26 26 24 24 17 10 1 1 0 0 0 0 0 0 0group 3 (n=56) 193 151 119 110 102 92 86 82 77 71 58 50 34 31 27 17 14 8 1 0 0total (n=193) a †among 23 lacscc patients who were included in the pre-specified group 2 interim analysis, there were no complete responses. presented at the 2020 fall clinical dermatology conference, october 29–november 1, virtual scientific meeting (encore of asco 2020 poster presentation). objectives • the primary objective of the phase 2 study was to evaluate the objective response rate (orr) by independent central review (icr) per response evaluation criteria in solid tumors version 1.1 (recist 1.1) (for scans)12 and modified world health organization (who) criteria (for photos). • key secondary objectives included orr per investigator review (inv), duration of response (dor) by icr and inv, progression-free survival (pfs) by icr and inv, os, complete response rate by icr, safety and tolerability, and assessment of health-related quality of life. durable disease control rate, defined as the proportion of patients with response or stable disease for at least 105 days, was also examined. • here, we present up to 3-year follow-up (median duration of follow-up for all patients: 15.7 months) from the largest and most mature prospective data set in advanced cscc. methods • empower-cscc-1 is an open-label, non-randomized, multicenter, international phase 2 study of patients with advanced cscc. • patients received cemiplimab 3 mg/kg every 2 weeks (q2w) (group 1; mcscc; group 2, lacscc) or cemiplimab 350 mg every 3 weeks (q3w) (group 3, mcscc) (figure 1). • the severity of treatment-emergent adverse events (teaes) was graded according to the national cancer institute common terminology criteria for adverse events (version 4.03). • the data cut-off was october 11, 2019. skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 431 brief articles microsporum canis infection presenting as cutaneous pseudolymphoma. case report and review of the literature lizy mariel paniagua gonzalez, md,1 adrian subrt, md,2 bernard gibson, md,2 1university of texas medical branch department of internal medicine galveston, tx 2university of texas medical branch department of dermatology galveston, tx microsporum canis is taxonomically classified to the ascomycota phylum and the arthrodermataceae family. it is a zoophilic dermatophyte infection commonly affecting cats, dogs, and other mammals. the fungi typically affect the hair, the skin, and rarely the nails, causing an ectothrix infection.1 in humans, m. canis causes dermatophytosis, infecting children most frequently. it has been reported to cause tinea capitis, tinea faciei, tinea corporis, tinea pedis, and tinea unguium[1]. microsporum canis has a worldwide distribution with the highest prevalence in iran[1]. dermatophyte invasion of the skin leads to lymphocytic inflammation in the dermis that, depending on the severity of the reaction, can be confused with malignant lymphocytic infiltration.1-3 we describe a case of a 63 year old patient who presented with pruritic, erythematous, thin, annular, scaling plaques localized to the forearms, abdomen and left hand. the patient was initially treated as an allergic reaction with triamcinolone. a biopsy performed by the patient’s primary care physician raised concern for a cutaneous lymphoma. after referral to dermatology, a koh and fungal culture were performed which suggested a dermatophyte infection caused by microsporum canis. the patient was treated with oral fluconazole for a month and a half with resolution of most of the lesions as well as his symptoms. this clinical improvement supported the diagnosis of tinea corporis instead of a cutaneous lymphoma. this case illustrates that differentiating between cutaneous pseudolymphoma and microsporum canis cutaneous infection mimicking histopathologically a cutaneous t cell lymphoma is discussed. a 63 year old male presented with pruritic, erythematous thin annular, scaling plaques localized to the forearms, abdomen and left hand. a primary care physician’s biopsy raised concern for a cutaneous lymphoma. at the dermatology clinic, a koh and fungal culture suggested a dermatophyte infection caused by microsporum canis. the patient was treated with oral fluconazole with resolution of most of the lesions and symptoms. this clinical improvement supported the diagnosis of tinea corporis instead of a cutaneous lymphoma. to the best of our knowledge, this is the first reported case of microsporum canis mimicking cutaneous t-cell lymphoma. abstract introduction skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 432 figure 1 (a) left hand with erythematous, thin, annular, scaling plaques at presentation to dermatology clinic. (b) right forearm with several erythematous, scaly plaques at presentation to dermatology clinic. (c) low magnification of the right forearm biopsy. (d & e) perivascular t-lymphocytic infiltration without epidermotropism on h&e 100x and h&e 200x, respectively. (f) atypical lymphocytes on h&e 400x. cutaneous lymphoma can be challenging. proper history, physical exam, and laboratory testing are essential to accurately diagnose cutaneous pseudolymphoma. to the best of our knowledge, this is the first reported case of microsporum canis infection mimicking cutaneous t-cell lymphoma. a 63 year old male with past medical history of hypertension, diverticulosis, and prostate cancer treated with prostatectomy in 2014, presented to his primary care physician (pcp) for evaluation of a rash that initially started on his right forearm about one month prior. the patient started to develop new lesions; five additional lesions appeared on figure 2: (a) cd 3 immunostaining. the lymphocytic infiltrate clearly shows a positive cd 3 stain. (b) cd 20 immunostaining. the infiltrate is negative for cd 20. his arms and one on his abdomen (figure 1a1b). the lesions were pruritic and occasionally some of the lesions had slight serous drainage. at his initial pcp visit, he was prescribed triamcinolone for presumed allergic reaction. the patient stated that the steroid helped with the itching, however, new lesions appeared on the left hand. the pcp performed a biopsy of the original lesion on the right forearm. it showed atypical perivascular t-lymphocytic infiltrate with cd3 positive, cd20 negative lymphocytes (figure 2a-b) without apparent epidermotropism, (figure 1c-f). the patient was told that he had cutaneous lymphoma and was referred to dermatology and oncology. at the dermatology clinic, the patient stated that he continued to itch and was taking hydroxyzine to relieve his symptoms. the cutaneous lesions raised clinical suspicion for a fungal infection. significantly, he reported that he was in contact with many stray cats, as he volunteered at an animal shelter on a weekly basis. for this reason, a koh preparation and a skin biopsy of the left radial wrist were performed. the koh preparation suggested the presence of dermatophytes (figure 3c-d). a fungal culture was performed which grew microsporum canis (figure 3e). the biopsy showed intracorneal hyphae with a positive periodic acid-schiff (pas)-stain, consistent with tinea corporis, no malignancy. the patient was told that he likely had inflammatory tinea corporis not lymphoma. case report a a a b e c d f a b skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 433 figure 3: (a) right forearm with few erythematous papules and postinflammatory hyperpigmentation (pih). (b) left hand with pih and few erythematous papules. (a&b) resolving lesions after one month of fluconazole treatment. (c) spindle-shaped, long, thick-walled macroconidia of microsporum canis. (d) koh preparation showing hyphae under light microscopy. (e) fungal culture growing m. canis. he was started on fluconazole 200 mg daily for one month. he returned to clinic one month later, and his lesions had improved significantly. the patient only had a few erythematous papules remaining, with post inflammatory hyperpigmentation. he continued fluconazole 200 mg daily for another 15 days and was told to avoid animal shelters (figure 3a-3b). at return to clinic two weeks later, there were no new lesions present, he was essentially clear, and continued to be asymptomatic. the patient presented with pruritic, erythematous, thin, annular, scaling plaques that could be the manifestation of a large number of conditions from benign entities to life-threatening lesions. this patient illustrates a challenging differential diagnosis that ranged from allergic reaction to cutaneous lymphoma. his initial evaluation suggested lymphoma, which on further evaluation, was shown to be a dermatophyte infection. pseudolymphoma is an inflammatory response with t-cell and/or b-cell lymphoproliferative infiltrate that may simulate cutaneous lymphoma.2 t-cell pseudolymphoma typically presents as an erythematous patch and/or plaque that can have scale. b-cell pseudolymphoma typically manifests as singular or multiple erythematous to purple nodules.4 both tend to have pruritus. this clinical presentation is similar to that of cutaneous lymphoma. there are several known and idiopathic causes that can lead to the development of pseudolymphoma. organisms that have been reported to cause pseudolymphoma include trichophyton rubrum5, stenotrophomonas maltophilia6, helicobacter pylori, secondary syphilis, arthropod reactions, and viral infections such as orf, milker's nodule, herpes simplex, herpes zoster, and molluscum contagiosum7. additionally, diseases such as lichenoid pigmented purpuric dermatosis, lichen sclerosus, inflammatory stage of morphea, lupus panniculitis, and contact dermatitis can present as pseudolymphoma. drug eruption and tattoos have also been linked to developing pseudolymphoma.3 differentiating a cutaneous lymphoma from pseudolymphoma histopathologically can be challenging. this patient’s biopsy showed a cd3-positive and cd 20-negative lymphocytic infiltration, which indicates the presence of only t-cells on histology. pseudolymphoma classically contains a mixture of t cells, b cells, macrophages, and dendritic cells.3 this case had primarily t cells, which can make the differential diagnosis even more difficult to establish. tcell lymphomas such as mycosis fungoides, as well as sézary syndrome would need to be considered. the literature suggests that on histopathology the presence of a mixture of histiocytes, eosinophils, plasma cells and lymphocytes is more suggestive of a discussion d c a b skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 434 cutaneous pseudolymphoma than of cutaneous lymphoma.8. if there is nuclear atypia, it tends to be mild compared to that seen in cutaneous t or b cell lymphoma. pseudolymphoma does not usually have epidermotropism of t cell infiltrate that is often seen in cutaneous lymphoma.9 in this case, microsporum canis infection was the cause of the pseudolymphoma. microsporum canis has been reported as a mimicker of several other diseases. there are reports of m. canis causing tinea faciei simulating sweets syndrome.10 this dermatophyte has also simulated pemphigus erythematosus11 and neonatal lupus.12 it is crucial to distinguish between pseudolymphoma and cutaneous lymphoma as it essential for proper treatment of the patient. proper history, physical exam, koh fungal preparation, specific staining for potential etiological agents, and cultures are ideal in determining the accurate diagnosis. to the best of our knowledge, this is the first reported case of microsporum canis mimicking cutaneous t-cell lymphoma. conflict of interest disclosures: none. funding: none. corresponding author: lizy mariel paniagua department of internal medicine university of texas medical branch galveston, tx email: lmpaniag@utmb.edu references: 1. segundo c, martínez a, arenas r, fernández r, cervantes ra. superficial infections caused by microsporum canis in humans and animals. rev iberoam micol. 2004;21:39-41. 2. dragonetti, e., cianchini, g., mastrangelo, l., mellone, p., baldi, a. cutaneous pseudolymphoma: a case report. in vivo. 2004;18(5):549-552. 3. kash, n., vin, h., danialan, r., prieto, v., duvic, m., stenotrophomonas maltophilia with histopathological features mimicking cutaneous gamma/delta t-cell lymphoma. int. j. of infect dis. 2015;30:7-9. 4. bergman, r. pseudolymphoma and cutaneous lymphoma: facts and controversies. clinc in dermatol. 2010;28(5):568-574. 5. terada, t. cutaneous pseudolymphoma: a case report with an immunohistochemical study. int. j. clin. exp. pathol. 2013;6(5):966-972. 6. viera, m.h, costales, s.m., regalado, j., alonso-llamazares, j. inflammatory tinea faciei mimicking sweet’s syndrome. actas dermosifiliogr. 2013;104(1):75-76. 7. amano, h., kishi, c., yokoyama, y., shimizu, a., anzawa, k., mochizuki, t., ishikawa, o., microsporum canis infection mimics pemphigus erythematosus. indian j. dermatol. 2013;58(3):243. 8. bangert, c., wheeland, r., orlick, k., levine, n. tinea capitis due to microsporum canis mimicking neonatal lupus in a 10-day neonate. j. am. acad. dermatol. 2005; 52(3):130. 9. kerl, h, fink-puches, r, cerroni, l. diagnostic criteria of primary cutaneous bcell lymphomas and pseudolymphoma. keio j. med. 2001; 50(4):269-273. 10. burg, g., kerl, h, schmoeckel, c. differentiation between malignant b-cell lymphoma and pseudolymphoma of the skin. j dermatol surg. oncol. 1984; 10(4): 271-275. 11. fung, m.a. epidermotropism vs, exocytosis of lymphocytes 101:definition of terms. j cutan pathol. 2010; 37(5):525529. mailto:lmpaniag@utmb.edu skin july 2018 volume 2 issue 4 copyright 2018 the national society for cutaneous medicine 256 brief article cutaneous manifestations of disseminated histoplasmosis in a patient with aids luis j. borda md a , kate e. oberlin md a , anna j. nichols md phd a a department of dermatology and cutaneous surgery, university of miami miller school of medicine, miami, fl disseminated histoplasmosis is typically an opportunistic infection in states of immunosuppression, such as in human immunodeficiency virus (hiv)-infected patients. the initial infection primarily affects the lungs, but in patients with acquired immunodeficiency syndrome (aids) with low cd4 t-cell counts the disease can evolve into disseminated histoplasmosis leading to poor prognosis. 1 the clinical manifestations of disseminated histoplasmosis depend on the severity of immunodeficiency of the host and the degree of exposure to the pathogen. 1,2 patients often present with hepatosplenomegaly, pancytopenia, gastrointestinal and oropharyngeal lesions. 2 furthermore, cutaneous lesions have been described in 10-15% of cases abstract introduction: disseminated histoplasmosis is often seen in immunocompromised individuals, such those with acquired immunodeficiency syndrome (aids). the initial infection mainly involves the lungs but it may develop into a disseminated form especially in immunocompromised patients. since it can be a systemic disease with cutaneous manifestations, dermatologists must be able to recognize its clinical presentation to ensure prompt management. case: we present a man in his 50s with past medical history of aids who developed disseminated histoplasmosis with skin and gastrointestinal involvement over a one-month period of time. despite receiving induction therapy with intravenous amphotericin b followed by oral itraconazole, the patient expired. his death was attributed to his persistently low cd4 t-cell count and secondary bacteremia. discussion: this condition should be recognized early and treated aggressively. however, patients with multiple comorbidities are at increased risk of mortality even despite adequate treatment. this case highlights the significant mortality risk of disseminated histoplasmosis in patients with aids. introduction skin july 2018 volume 2 issue 4 copyright 2018 the national society for cutaneous medicine 257 of disseminated histoplasmosis. 3 we describe a patient with disseminated histoplasmosis in which we highlight that the clinical diagnosis can be challenging and prompt treatment is critical. a man in his 50s with aids and a cd4 count of 3 cells/mm 3 was admitted for a 1month history of malaise, fever, diarrhea and a new skin rash. he reported that the pruritic rash began on his face before spreading to his bilateral upper extremities. he denied a history of a similar rash in the past and had no prior treatment. he was undomiciled and denied recent travel. the patient was not compliant with antiretroviral medications. physical examination revealed a cachectic and ill-appearing adult man with numerous skin-colored firm papules, some with overlying excoriations, involving his face, bilateral upper extremities and dorsal hands (figure 1a and b). initial laboratory examination was notable for an elevated lactate dehydrogenase (ldh), leukopenia and acute kidney injury. punch biopsy specimens from the distal left upper extremity were performed for histopathological analysis and tissue culture. skin biopsy demonstrated pseudoepitheliomatous hyperplasia and extensive perivascular macrophage infiltrates containing numerous tiny intracellular organisms, highlighted by the gomori methanamine silver (gms) stain (figure 2a and b). tissue culture from a lesion identified histoplasma capsulatum and h. capsulatum serum antigen was positive. the diagnosis of disseminated histoplasmosis was made. given the patient’s severity of symptoms, a bone marrow biopsy was performed and was negative for involvement. the patient received induction therapy with intravenous amphotericin b for one week and was then continued on oral itraconazole therapy 200 mg twice daily. the patient’s antiretroviral therapies were reinitiated. unfortunately, due to coexisting morbidities, persistently low cd4 count and complicating bacteremia, the patient ultimately expired. figure 1. (a) photograph from clinical examination shows numerous 1-5mm indurated skin-colored papules on the forehead and bilateral malar cheeks; (b) coalescing similar lesions observed on the distal upper extremities. figure 2. histopathological findings from the upper extremity show characteristic intracellular 2-4 µm yeast forms within the cytoplasm of macrophages (a), which are further highlighted by gms staining (b) (h&e, x40). case report skin july 2018 volume 2 issue 4 copyright 2018 the national society for cutaneous medicine 258 histoplasmosis is a dimorphic fungal infection caused by histoplasma capsulatum and is the most prevalent endemic mycosis in the united states. birds and bats serve as the primary reservoirs with endemic areas in the midwest and mississippi regions. 4 high-risk areas include caves, construction sites, and chicken coops, locations in which spores are inhaled from the soil by a susceptible host. immunocompetent hosts may present with subclinical disease, however, with immunosuppression, dissemination of disease can occur. 5 the most common sites of involvement include the lung, spleen, lymph nodes, bone marrow and liver; dissemination to the skin occurs infrequently. 2,5 . risk factors for dissemination include immunodeficiency, extremes of age, and immunosuppression. a cd4 count of less than 50 cells/mm 3 has been reported in association with disseminated cases in patients with aids. 6 tnfα inhibitor therapy has been implicated in 74 cases of disseminated disease in a recent study. 7 the clinical presentation of disseminated histoplasmosis manifests in a variety of cutaneous presentations. oral ulcerations are the most common associated findings; however, non-specific papules, nodules and plaques may also arise on the face, extremities and trunk [2]. additional presentations include psoriasiform lesions, diffuse erythroderma, purpura and even hyperpigmentation secondary to adrenal involvement with resulting addison’s disease. 8 the differential diagnosis in our patient included pruritic papular eruption of hiv, eosinophilic folliculitis and opportunistic infections including cryptococcosis, blastomycosis, coccidiomycosis, penicillinosis, histoplasmosis, and leishmaniasis. the characteristic histopathologic features of histoplasmosis, namely intracellular 2-4 µm yeast forms within the cytoplasm of macrophages surrounded by an artefactual halo of clearing were demonstrated in our case. other diseases manifesting with similar appearing intracellular organisms engulfed by macrophages include leishmaniasis, granuloma inguinale, rhinoscleroma and penicillinosis. additionally, the organisms are strikingly similar to those seen in leishmaniasis, however, they lack a kinetoplast and are more evenly distributed throughout the cytoplasm. gms and pas stains assist in the correct diagnosis. the work-up involves histologic examination, and the gold standard of diagnosis is fungal culture. 9,10 determination of the urinary or serum histoplasma antigen can be helpful in monitoring and guiding treatment response. 10 laboratory evaluation for anemia, transaminitis, bilirubinemia, uremia and hypoalbumenia can be predictive factors for more severe disease within the aids population. 11 these patients should be recognized early and treated aggressively. 12 treatment involves initial intravenous amphotericin b therapy followed by oral itraconazole therapy twice daily. according to the 2007 infectious diseases society of america (idsa) guidelines, itraconazole therapy can be discontinued in disseminated cases in patients with aids once the following criteria are met: 12 months of discussion skin july 2018 volume 2 issue 4 copyright 2018 the national society for cutaneous medicine 259 itraconazole therapy, cd4 count of at least 150 cells/mm 3 , negative fungal blood cultures, and serum and urine antigen levels less than 4 u/ml. 10 our patient was treated accordingly, however, due to coexisting morbidities and low cd4 count, the patient ultimately expired. this case serves to highlight that disseminated histoplasmosis may result in substantial morbidity in critically ill patients, especially in patients with aids. these patients presenting with disseminated disease are significantly ill and require prompt recognition and management to maximize the efficacy of treatment. conflict of interest disclosures: none funding: none corresponding author: anna j. nichols, md, phd 1600 nw 10 th avenue rmsb 2023a miami, fl 33135 305-243-6734 (office) a.nichols@med.miami.edu references: 1. kauffman ca. diagnosis of histoplasmosis in immunosuppressed patients. curr opin infect dis. 2008;21(4):4215. 2. goodwin ra, jr., shapiro jl, thurman gh, thurman ss, des prez rm. disseminated histoplasmosis: clinical and pathologic correlations. medicine (baltimore). 1980;59(1):1-33. 3. assi ma, sandid ms, baddour lm, roberts gd, walker rc. systemic histoplasmosis: a 15-year retrospective institutional review of 111 patients. medicine (baltimore). 2007;86(3):162-9. 4. bahr nc, antinori s, wheat lj, sarosi ga. histoplasmosis infections worldwide: thinking outside of the ohio river valley. curr trop med rep. 2015;2(2):70-80. 5. wheat lj, slama tg, zeckel ml. histoplasmosis in the acquired immune deficiency syndrome. am j med. 1985;78(2):203-10. 6. nacher m, adenis a, blanchet d, vantilcke v, demar m, basurko c, et al. risk factors for disseminated histoplasmosis in a cohort of hiv-infected patients in french guiana. plos negl trop dis. 2014;8(1):e2638. 7. vergidis p, avery rk, wheat lj, dotson jl, assi ma, antoun sa, et al. histoplasmosis complicating tumor necrosis factor-alpha blocker therapy: a retrospective analysis of 98 cases. clin infect dis. 2015;61(3):409-17. 8. pastor ta, holcomb mj, motaparthi k, grekin sj, hsu s. disseminated histoplasmosis mimicking secondary syphilis. dermatol online j. 2011;17(11):10. 9. moreno-coutino g, hernandez-castro r, toussaint-caire s, montiel-robles m, sanchez-perez fs, xicohtencatl-cortes j. histoplasmosis and skin lesions in hiv: a safe and accurate diagnosis. mycoses. 2015;58(7):413-5. 10. wheat lj, freifeld ag, kleiman mb, baddley jw, mckinsey ds, loyd je, et al. clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the infectious diseases society of america. clin infect dis. 2007;45(7):807-25. 11. adenis a, nacher m, hanf m, vantilcke v, boukhari r, blachet d, et al. hiv-associated skin july 2018 volume 2 issue 4 copyright 2018 the national society for cutaneous medicine 260 histoplasmosis early mortality and incidence trends: from neglect to priority. plos negl trop dis. 2014;8(8):e3100. 12. nacher m, adenis a, mc donald s, do socorro mendonca gomes m, singh s, lopes lima i, et al. disseminated histoplasmosis in hiv-infected patients in south america: a neglected killer continues on its rampage. plos negl trop dis. 2013;7(11):e2319. v2 draft plaplus fc 10042020 combining dna and rna analyses enhances non-invasive early detection of cutaneous melanoma stephanie r jackson cullison, md, phd1, laura k ferris, md, phd2, zuxu yao, phd3 , claudia ibarra3, michael d howell, phd3, and burkhard jansen, md3 1department of dermatology, new york university school of medicine, new york, ny, 2department of dermatology, university of pittsburgh, pittsburgh, pa, 3dermtech, inc, la jolla, ca methods synopsis 1.gerami p et al. development and validation of a non-invasive 2gene molecular assay for cutaneous melanoma. j am acad dermatol, 2017;76(1)114-120.e2 2.ferris l et al. noninvasive analysis of high-risk driver mutations and gene expression profiles in primary cutaneous melanoma. j invest dermatol, 2019; 139(5):1127-1134 3.jackson s et al. risk stratification of severely dysplastic nevi by non-invasively obtained gene expression and mutation analyses. skin, 2020, 4(2) 4.robinson j et al. caring for melanoma survivors with self-detected concerning moles during covid 19 restricted physician access: a cohort study. skin, 2020, 4(3) to summarize available data and assess the real-world use of combining linc00518 and prame gene expression analyses with tert promoter mutation mutation analyses. the pigmented lesion assay (pla) is a gene expression test enhancing early melanoma detection. the test uses a proprietary non-invasive sample collection platform to objectively rule out melanoma and guide biopsy decisions. the pla has been evaluated in over 60,000 patients with approximately 90% (54,000) of patients avoiding surgical biopsies due to negative results. the test’s negative predictive value of >99% has been validated in long-term follow-up studies. combined with the rapid and painless application, the pla is an attractive solution that misses fewer melanomas while reducing costs. clinicians follow the guidance of the test in 98% of cases corroborating high clinical utility. to further improve the high performance of the pla, rna and dna analyses were combined in a new test termed plaplus. plaplus combines gene expression analyses for linc00518 and prame with tert promoter mutation analyses thereby elevating the test’s overall sensitivity from 91% to 97%. the individual sensitivity numbers of these genomic targets on cases with consensus diagnoses of melanoma were 84% (linc00518), 83% (prame), and 73% (tert). additional studies in real-world use cohorts (n=1,415) demonstrated the presence of tert promoter mutations in up to 24% of pla positive and 12% of pla negative tests. tert 146g>a mutations were the most frequently observed mutational change (48%). tert 124g>a (30%) and tert138g>a (12%) as well as tert 139g>a mutations (10%) were also detected. plaplus enhances the early detection of melanoma by combining dna and rna analyses of non-invasively collected samples of pigmented skin lesions clinically suspicious of melanoma. all clinical studies were irb approved. gene expression analyses were performed by rt-pcr as previously described. mutation analyses were performed by sanger sequencing. objectives conclusions references conflict of interest disclosures: srjc and lkf are advisors and/or investigators, zy, ci, mdh and bj are employees of dermtech • adding tert promotor mutation analyses to linc00518 and prame gene expression analyses further increases test’s sensitivity from 91% to 97%. • the individual target’s sensitivity numbers are 84%, 83% and 73% for linc00518, prame and tert, respectively. • adding tert promotor mutation analyses to linc00518 and prame gene expression analyses further increases test’s negative predictive value from 99.3% to 99.6%. • both pla and plaplus lend themselves to remote sample collection under physician guidance in teledermatology environments. results efforts to further improve the high performance of the pla led to a strategy that combines rna and dna analyses to create a new test termed plaplus. plaplus combines gene expression analyses for linc00518 and prame (two targets overexpressed in melanoma) with tert promoter mutation analyses (figure 1) which elevates the test’s overall sensitivity from 91% to 97% (figure 2). individual sensitivity numbers of these genomic targets on cases with consensus diagnoses of melanoma were 84% (linc00518), 83% (prame), and 73% (tert). plaplus conservatively focuses on maximizing sensitivity while maintaining a high specificity of 62%. adding tert promotor mutation analyses to linc00518 and prame further increases the test’s negative predictive value from 99.3% to 99.6%. studies in real-world use cohorts (n=1,415) demonstrated the presence of tert promoter mutations in up to 24% of pla positive and 12% of pla negative tests. while the biologic significance of different types of tert mutations is the subject of ongoing studies, tert 146g>a mutations were the most frequently observed mutational change (48%) in our study cohorts. tert 124g>a (30%) and tert138g>a (12%) as well as tert 139g>a mutations (10%) were also detected. increasing genomic atypia that may precede morphologic atypia can be found on the spectrum of pigmented skin lesions from benign nevi to melanoma. figure 1: plaplus genomic targets. figure 2: plaplus combines gene expression and mutation analyses to further enhance early melanoma detection. • linc is detected in 84% of histopathologically confirmed melanomas • recently discovered marker • member of a rapidly growing family of regulatory rna molecules that play a role in melanoma proliferation and invasion linc00518 long intergenic non-coding rna 518 prame preferentially expressed antigen in melanoma • prame is detected in 83% of histopathologically confirmed melanomas1 • well described in many tumors, independently validated by haqq, myriad, castle • promotes tumor progression by interfering with retinoic acid receptor signaling tert telomerase reverse transcriptase • tert promoter mutations are detected in 73% of histopathologically confirmed melanomas • mutations lead to oncogenesis through functional increases in tert protein, telomerase activity, telomere length, cell immortalization and proliferation • associated with histopathologic features of aggressiveness and poor survival in melanoma pl a pl a p lu s impact of a prognostic 40-gene expression profiling test on clinical management decisions for high-risk cutaneous squamous cell carcinoma graham h. litchman,1 alison l. fitzgerald,2 sarah j. kurley,2 robert w. cook,2 darrell s. rigel3 1clinical research fellow, national society for cutaneous medicine, new york, ny 2castle biosciences, inc., friendswood, tx 3clinical professor of dermatology, nyu grossman school of medicine, new york, ny synopsis one million cases of cutaneous squamous cell carcinoma (cscc) are estimated to be diagnosed annually with an mortality rate of 1.5%-2%.1 a 40-gene expression profile (40gep) test that assesses the biology of a primary cscc tumor was recently validated for determining metastatic potential.2 the 40-gep test classifies patients into three risk groups: low (class 1), high (class 2a), and highest (class 2b) risk for developing regional or distant metastasis within 3 years post-diagnosis. to assess the potential utility of the 40-gep test for guiding cscc patient management decisions, a clinical impact study was undertaken to determine if more precise risk assessment through 40-gep testing would alter physicians’ management decisions. references conclusions funding & disclosures objective dermatology clinicians (dermatologists, nurse practitioners [nps] and physician assistants [pas]) attending a national dermatology conference were presented with 40-gep test validation data. they were asked to rate clinicopathological features and molecular test results to assess their opinion of how concerning each is to cscc prognosis (figure 1). vignettes describing patients with high-risk features were presented and clinicians were then asked to select a treatment plan using pre-test (no 40-gep results), then, post-test (40-gep class 1, 2a, or 2b results) methodology. results figure 1. clinician assessment of perceived risk of metastasis with molecular 40-gep class and clinicopathologic features in cscc* table 2. clinical characteristics of patient vignettes table 1. clinician demographics (n=162) figure 2. effect of 40-gep test results on clinicians’ management decisions table 3. comparison of changes by management modality • results from this study support that dermatologists, nps and pas understand the prognostic risk associated with each 40-gep class and can appropriately incorporate 40-gep test results to assist in management decisions for high-risk cscc patients. • management was altered in a risk-appropriate manner to align with metastatic risk as determined by 40-gep class results. • the findings of this study suggest the possibility of more appropriate management and efficient resource allocation for cscc patients when the 40-gep test information is included in prognostic risk assessment. 1. skin cancer foundation. https://www.skincancer.org/ 2. wysong, et al. 2020 under review jaad this study was sponsored in full by castle biosciences, inc. ghl participated in a research fellowship, which was partially funded by castle biosciences, inc. dsr is a consultant and a member of the speaker bureau for castle biosciences, inc. alf, sjk, and rwc are employees and also hold stock options at castle biosciences, inc. years in practice resident 11.7% 1-10 years 40.7% 11-20 years 14.2% 21-30 years 19.8% >30 years 13.6% specialty dermatologist 77.2% dermatologist/mohs surgeon 11.1% dermatopathologist 1.2% dermatology np/pa 8.6% other 1.9% newly diagnosed invasive cscc patients seen in 2019 <50 31.5% 50-100 34.0% 100-200 16.7% 200-400 14.2% >400 3.7% high-risk cscc patients encountered ≤1% 12.3% 2-5% 34.0% 6-10% 30.2% 11-20% 14.8% >20% 8.6% cscc staging system used i do not use any of these methods 30.9% i am not aware of these methods 13.0% i use a cscc staging system: 56.1% ajcc7 17.6% ajcc8 58.2% bwh 24.2% np/pa = nurse practitioner/physician assistant, ajcc7 or ajcc8 = american joint committee on cancer staging manual edition 7 or 8, bwh = and brigham and women’s hospital vignette age, sex tumor location size depth of lesion margin status histological differentiation ajcc stage 1 67, male scalp 1.2 cm 1.2mm well-defined poor t1 2 67, male scalp 1.2 cm beyond subcutaneous fat well-defined well t3 40-gep class p value for comparison to feature <0.0001 <0.05 n.s. class 1 all other features ----class 2a perineural invasion, immunosuppressed patient, class 1 and 2b invasion beyond subcutaneous fat mask area, scalp >1cm, below neck >2cm class 2b mask area, scalp >1cm, below neck >2cm, class 1 and 2a invasion beyond subcutaneous fat perineural invasion, immunosuppressed patient 0% 20% 40% 60% 80% 100% no 40-gep class 1 class 2a class 2b no 40-gep class 1 class 2a class 2b sentinel lymph node biopsy (slnb) avoid consider recommend vignette 1 vignette 2 0% 20% 40% 60% 80% no 40-gep class 1 class 2a class 2b no 40-gep class 1 class 2a class 2b follow-up intervals 1-2x per year 2-4x per year 4-12x per year vignette 1 vignette 2 0% 20% 40% 60% 80% 100% no 40-gep class 1 class 2a class 2b no 40-gep class 1 class 2a class 2b nodal imaging none nodal us or ct 1x per yr nodal us or ct 4x per yr vignette 1 vignette 2 0% 20% 40% 60% 80% 100% no 40-gep class 1 class 2a class 2b no 40-gep class 1 class 2a class 2b adjuvant radiation avoid consider recommend vignette 1 vignette 2 0% 20% 40% 60% 80% 100% no 40-gep class 1 class 2a class 2b no 40-gep class 1 class 2a class 2b adjuvant chemotherapy avoid consider recommend vignette 1 vignette 2 management modality* vignette 1 vignette 2 class 1 class 2a class 2b class 1 class 2a class 2b reduce increase reduce increase reduce increase reduce increase reduce increase reduce increase follow-up 47 4 18 22 4 86 43 4 20 15 1 72 sentinel lymph node biopsy 59 1 11 30 2 133 83 5 25 19 0 118 nodal imaging 35 4 12 20 2 103 44 4 26 13 1 89 adjuvant radiation 53 1 11 25 1 133 71 2 27 17 2 117 adjuvant chemotherapy 34 1 9 26 4 112 53 2 17 15 1 104 *fisher’s exact test with freeman-halton extension indicated that each row had statistically significant differences p<0.0001 when comparing class 1, 2a, and 2b for a given modality. methods to determine how results from the prognostic 40-gep test would impact clinician management decisions and how their choices would align with a risk-directed management plan for high-risk cscc, consistent with recommendations from the national comprehensive cancer network (nccn). 40-gep class p value for comparison to 'no 40-gep' vignette 1 vignette 2 <.0001 <.05 ns <.0001 <.05 ns class 1 slnb f/u, chemo, imaging, rt ---slnb, rt f/u, imaging, chemo ---class 2a ------f/u, slnb, imaging, chemo, rt ------f/u, slnb, imaging, chemo, rt class 2b f/u, slnb, imaging, chemo, rt ------f/u, slnb, imaging, chemo, rt ------slnb = sentinel lymph node biopsy, f/u = follow-up, chemo = adjuvant chemotherapy, imaging = nodal imaging, rt = adjuvant radiation. using a friedman’s test with dunn’s multiple comparisons correction, statistical significance was determined for each vignette when all post-test 40-gep results were compared to pre-test 40-gep (no 40-gep) * graphs represent percentage of clinicians who would develop either a low (blue bar), moderate (orange bar), or high (red bar) intensity management plan based on pre-test (no 40gep data), then, post-test (class 1, 2a, or 2b) results. results cont. *all clinicians surveyed were asked to rate, on a scale of 1-10 (1, lowest; 10, highest), the level of risk for metastasis associated with each of the features presented, independent of each other. median values are plotted with error bars denoting 95% confidence intervals. p values for comparisons of risk between two features are shown in the table and reflect friedman tests with a dunn’s correction for multiple comparisons. increasing risk https://www.skincancer.org/ introduction • plaque psoriasis is a debilitating, chronic, immune-mediated skin disorder that impairs patients’ health-related quality of life (hrqol) and productivity1 • treatment outcomes for plaque psoriasis based on the absolute psoriasis area and severity index (pasi) are indicative of an individual patient’s disease severity at the time of analysis2 — absolute pasi may be more clinically meaningful than percentage change in pasi from baseline captured by scores such as pasi 75 (≥75% reduction from baseline pasi)2 — although a consensus therapeutic target has yet to be defined, a recent analysis reported that attainment of an absolute pasi of ≤2 translates to meaningful improvements in clinical and hrqol outcomes2 • previous studies have demonstrated that an absolute pasi ≤2 correlates with pasi 90 (≥90% improvement from baseline pasi), static physician’s global assessment (spga) score of 0/1 (range, 0–5; higher scores indicate greater disease severity), and dermatology life quality index (dlqi) of 0/1 (range, 0–30; higher scores indicate worse hrqol)2 • deucravacitinib (bms-986165) is an oral, selective, allosteric inhibitor of tyrosine kinase 2 (tyk2), an intracellular enzyme involved in key cytokine signaling pathways in plaque psoriasis pathogenesis3 — in a phase 2, double-blind, randomized trial in patients with moderate to severe plaque psoriasis (nct02931838), 67%–75% of patients treated with deucravacitinib at doses of 3 or 6 mg twice daily (bid) or 12 mg once daily (qd) achieved pasi 75 at week 12 (primary endpoint) vs 7% with placebo (p<0.001)3 — deucravacitinib had a favorable safety and tolerability profile, and was associated with low rates of treatment discontinuation3 objective • this post hoc analysis of the phase 2 trial compared the efficacy of deucravacitinib vs placebo based on absolute pasi over time up to week 12 materials and methods inclusion criteria • adults with body mass index of 18–40 kg/m2 • moderate to severe plaque psoriasis for ≥6 months affecting ≥10% of body surface area — pasi ≥12 (range, 0–72; higher scores indicate greater disease severity) — spga ≥3 • eligible for phototherapy or systemic therapy exclusion criteria • diagnosis of nonplaque psoriasis or other immune-mediated condition requiring concomitant systemic immunosuppressant therapy • history or evidence of specific infections (eg, hiv or hepatitis b or c infection) or risk of tuberculosis • previous lack of response to any therapeutic agent targeting the tyk2 pathway (eg, interleukin-12/-23 pathways) treatment • patients were randomized equally to 1 of 5 oral doses of deucravacitinib (3 mg every other day, 3 mg qd, 3 mg bid, 6 mg bid, or 12 mg qd) or matching oral placebo for 12 weeks study endpoints • this post hoc analysis assessed the following efficacy endpoints in the 3 most effective deucravacitinib dose groups (3 mg bid, 6 mg bid, 12 mg qd) vs placebo — mean absolute pasi over time — mean percentage change from baseline in absolute pasi over time — percentage of patients at week 12 who achieved an absolute pasi of ≤1, ≤2, ≤3, and ≤5 statistical analysis • this post hoc efficacy analysis was performed in the efficacy analysis population • absolute pasi over time and within predefined categories are expressed as patient numbers and percentages • patients who discontinued the treatment regimen early or who had a missing value at any time point had outcomes imputed as a nonresponse at that time point, regardless of response status at time of discontinuation results baseline demographics and disease characteristics • 179 patients were included in this post hoc analysis (deucravacitinib groups, n=134; placebo, n=45) • baseline demographics and disease characteristics of patients in each dose group are presented in table 1 — most patients were male (58%–82% across treatment groups), mean patient age was 43–47 years, and mean body mass index was 27–30 kg/m2 — baseline mean pasi was similar across treatment groups (18–19) — median disease duration was 13–20 years and 41%–44% of patients had received prior biologic therapy table 1. baseline demographics and disease characteristics3 deucravacitinib characteristic* placebo (n=45) 3 mg bid (n=45) 6 mg bid (n=45) 12 mg qd (n=44) demographic characteristics mean age, y 46 ± 12 46 ± 15 43 ± 13 47 ± 12 male sex, n (%) 37 (82) 26 (58) 35 (78) 30 (68) race, n (%) white 40 (89) 39 (87) 35 (78) 37 (84) asian 5 (11) 5 (11) 9 (20) 6 (14) other 0 1 (2) 1 (2) 1 (2) body weight, kg 96 ± 21 84 ± 18 84 ± 19 88 ± 24 body mass index, kg/m2 30 ± 6 28 ± 5 27 ± 5 29 ± 5 clinical characteristics median (range) disease duration, y 18 (2–48) 13 (1–61) 15 (1–55) 20 (1–47) prior use of biologic therapy, n (%) 20 (44) 19 (42) 20 (44) 18 (41) pasi† 19 ± 6 19 ± 8 18 ± 6 18 ± 5 dlqi‡ 13 ± 7 13 ± 5 11 ± 6 13 ± 7 body surface area, % 24 ± 13 24 ± 15 25 ± 13 21 ± 12 from n engl j med, papp k, gordon k, thaçi d, et al, phase 2 trial of selective tyrosine kinase 2 inhibition in psoriasis, 379(14):1313-1321. copyright © 2018 massachusetts medical society. reprinted with permission. bid, twice daily; dlqi, dermatology life quality index; pasi, psoriasis area and severity index; qd, once daily. * values are means ± sd unless otherwise noted. data have been rounded to the nearest integer. percentages may not total 100 because of rounding. †pasi ranges from 0–72, with higher scores indicating greater severity of psoriasis. ‡dlqi scores range from 0–30, with higher scores indicating worse quality of life. absolute pasi • deucravacitinib was associated with lower absolute pasi compared with placebo up to week 12 (figure 1) — each of the 3 deucravacitinib doses evaluated resulted in similar levels of improvement in median absolute pasi over time figure 1. median absolute pasi through week 12 0 5 10 15 20 25 35 30 40 45 a b so lu te p a si baseline week 4 week 8 week 12 3 mg bidplacebo 6 mg bid 12 mg qd deucravacitinib bid, twice daily; pasi, psoriasis area and severity index; qd, once daily. • deucravacitinib was also associated with greater reductions in mean percentage change from baseline in absolute pasi than placebo from week 1 to week 12 (figure 2) figure 2. mean percentage change from baseline in absolute pasi through week 12 0 2 6 104 8 12 3 mg bid placebo 6 mg bid 12 mg qd deucravacitinib time (weeks) -90 -80 -70 -60 -50 -40 -30 -20 -10 0 m e an ± s e p e rc e n ta ge c h an ge f ro m b as e li n e i n a b so lu te p a si bid, twice daily; pasi, psoriasis area and severity index; qd, once daily. • the percentages of patients achieving absolute pasi values of ≤1, ≤2, ≤3, and ≤5 at week 12 were higher in the deucravacitinib groups than in the placebo group (table 2) table 2. absolute pasi at week 12 patients achieving pasi threshold, % (intent-to-treat population) absolute pasi placebo (n=45) deucravacitinib 3 mg bid (n=45) deucravacitinib 6 mg bid (n=45) deucravacitinib 12 mg qd (n=44) deucravacitinib combined (n=134) ≤1 0 24.4 33.3 34.1 30.6 ≤2 0 46.7 44.4 50.0 47.0 ≤3 2.2 57.8 53.3 63.6 58.2 ≤5 8.9 73.3 64.4 77.3 71.6 bid, twice daily; pasi, psoriasis area and severity index; qd, once daily. patients who discontinued the treatment regimen early or who had a missing value at any time point had outcomes imputed as a nonresponse at that time point, regardless of response status at time of discontinuation. conclusions • this analysis suggests that deucravacitinib elicits a rapid response and is efficacious in achieving an absolute pasi of ≤2 in approximately 50% of patients and an absolute pasi ≤1 in approximately 30% of patients with moderate to severe plaque psoriasis — as mentioned earlier, an absolute pasi of ≤2 has been shown to be clinically meaningful for clinical and hrqol outcomes2 — mean percentage change from baseline in absolute pasi at week 12 was approximately 80% in deucravacitinib–treated patients • five ongoing phase 3 trials in plaque psoriasis (nct03624127, nct03611751, nct04167462, nct03924427, and nct04036435) involving deucravacitinib treatment will evaluate this further over a longer duration and in larger patient cohorts • pasi ≤2 has the potential to be an alternative therapeutic goal to percent pasi improvements and spga scores for patients with moderate to severe plaque psoriasis references 1. weigle n, mcbane s. am fam physician. 2013;87(9):626-633. 2. puig l et al. acta derm venereol. 2019;99(11):971-977. 3. papp k et al. n engl j med. 2018;379(14):1313-1321. acknowledgments • this work was sponsored by bristol myers squibb. professional medical writing from ann marie fitzmaurice, phd and editorial assistance were provided by peloton advantage, llc, an open health company, parsippany, nj, and were funded by bristol myers squibb. relationships and activities • bs: honoraria or consultation fees: abbvie, almirall, amgen, arena, boehringer ingelheim, bristol myers squibb, celgene, dermavant, dermira, eli lilly, gsk, janssen, kyowa hakko kirin, leo pharma, medac, meiji seika pharma, novartis, ortho dermatologics, pfizer, regeneron, sanofi-genzyme, sun pharma, ucb; speaker: abbvie, janssen, lilly, ortho dermatologics; scientific director (consulting fee): corrona psoriasis registry; investigator: abbvie, corrona psoriasis registry, dermavant, dermira • abg: grant/research funding (paid to institution): boehringer ingelheim, incyte, janssen-ortho, novartis, ucb, xbiotech; honoraria or consultation fees (paid to abg): abbott (abbvie), amgen, bristol myers squibb, celgene, eli lilly, incyte, janssen biotech, janssen-ortho, leo pharma, lilly icos, novartis, sun pharma, ucb, xbiotech, and avotres (no direct compensation received from avotres); stock options: xbiotech • dt: research support/principal investigator (clinical trials): abbvie, almirall, amgen, biogen idec, boehringer ingelheim, celgene, chugai, dermira, ds-pharma, eli lilly, galderma, gsk, janssen-cilag, leo pharma, msd, novartis, pfizer, regeneron, roche, sandoz-hexal, sanofi, ucb; consultant: abbvie, almirall, celgene, dignity, galapagos, leo pharma, maruho, mitsubishi, novartis, pfizer, xenoport; lectures: abbvie, almirall, amgen, ds-pharma, janssen, leo pharma, msd, novartis, pfizer, la roche-posay, sandoz-hexal, sanofi, target-solution, ucb; scientific advisory board: abbvie, amgen, celgene, ds-pharma, eli lilly, galapagos, janssen-cilag, leo pharma, morphosis, msd, novartis, pfizer, sandoz, sanofi, ucb • lp: grant/research support or participation in clinical trials (paid to institution): abbvie, almirall, amgen, boehringer ingelheim, celgene, eli lilly, janssen, leo pharma, novartis, pfizer, regeneron, roche, sanofi, ucb; honoraria or consultation fees (paid to lp): abbvie, almirall, amgen, baxalta, biogen, boehringer ingelheim, celgene, eli lilly, fresenius kabi, gebro, janssen, leo pharma, merck-serono, msd, mylan, novartis, pfizer, regeneron, roche, samsung bioepis, sandoz, sanofi, ucb; speakers bureau: celgene, eli lilly, janssen, msd, novartis, pfizer • mjc, sk, rk, and sb: employees and shareholders of bristol myers squibb an oral, selective tyrosine kinase 2 inhibitor, deucravacitinib (bms-986165), reduced absolute psoriasis area and severity index in a phase 2 trial in psoriasis bruce strober,1 alice b. gottlieb,2 diamant thaçi,3 luis puig,4 matthew j. colombo,5 sudeep kundu,5 renata kisa,5 subhashis banerjee5 1yale university, new haven, ct, and central connecticut dermatology research, cromwell, ct, usa; 2icahn school of medicine at mount sinai, new york, ny, usa; 3research institute and comprehensive center for inflammation medicine, university of lübeck, lübeck, germany; 4hospital de la santa creu i sant pau, universitat autònoma de barcelona, barcelona, spain; 5bristol myers squibb, princeton, nj, usa presented at the 2020 fall clinical dermatology conference: october 29−november 1, 2020; virtual meeting and at las vegas, nevada this poster may not be reproduced without written permission from the authors of this poster. email: http://www.globalbmsmedinfo.com skin may 2018 volume 2 issue 3 copyright 2018 the national society for cutaneous medicine 156 original research do second-time users of topical imiquimod have a more rapid onset of clinical response? stacy l. mcmurray md a , matthew reynolds, mpas pa-c b , matthew s. dinehart ba m.ed c , scott m. dinehart md b a university of tennessee department of dermatology, memphis tn b arkansas dermatology, little rock, ar c university of arkansas for medical sciences, little rock, ar abstract introduction: topical imiquimod is commonly used in dermatology for treatment of actinic keratoses (ak). prior studies in humans and mice have suggested the potential for immune recall with imiquimod based on higher degrees of ak clearance and activation of memory γδ t-cells in a mouse model. anecdotal reports suggest a more rapid time-to-onset of clinical response with second time use of imiquimod. however, the potential for immune recall demonstrated by time-to-onset of clinical response has not been formally investigated. objective: the primary objective of this study was to determine if there is a difference in time-to-onset of clinical response between naïve and prior users of topical imiquimod for the treatment of actinic keratoses. methods: a total of 92 patients were treated with 5% imiquimod cream for actinic keratoses of the head and neck. patients were instructed to apply 5% imiquimod cream to the affected areas once daily until reaching a therapeutic endpoint of crusting/scabbing. the primary endpoints in the study were time (days) to onset of erythema and time to onset of crusting/scabbing. results were self-reported. results: the average time (days) to onset of erythema was 5.48 ± 3.19 days in naïve users and 4.7 ± 2.91 days in prior users (p= 0.22). average time to onset of crusting/scabbing was 9.2 ± 4.34 days in naïve users and 9.02 ± 3.65 days in prior users (p=0.35). conclusion: our study revealed there is no difference in time-to-onset of erythema or scabbing/crusting with second-time use of imiquimod. while immune recall may be possible with use of imiquimod, the results of this study indicate that it may be independent of timeto-onset of clinical response. skin may 2018 volume 2 issue 3 copyright 2018 the national society for cutaneous medicine 157 topical imiquimod is a commonly used therapy in dermatology, approved for treatment of actinic keratoses (ak), genital warts, and superficial basal cell carcinoma. 1 it is also frequently used off-label for treatment of select squamous cell carcinoma in-situ, melanoma in-situ, and a variety of other dermatologic conditions. 2 imiquimod was initially thought to exert antiviral and antitumoral effects via selective agonism of toll-like receptor 7 (tlr7). recent studies have revealed that its mechanism of action is more complex. imiquimod stimulates innate and adaptive immunity not only via tlr7, but also through toll-like receptor 8 (tlr8), the nuclear factor kappa b (nf-κb) pathway, the hedgehog pathway (via adenylate cyclase), and the opioid growth factor receptor (ogfr) (figure 1). 3,4 many ak treatment protocols utilizing imiquimod dictate several courses of therapy separated by rest periods. in addition, some patients will use a second course of imiquimod months or even years after their initial course. patients and physicians have anecdotally reported that time-to-onset of clinical response is shorter in patients who have previously used imiquimod, proposing the generation of immune recall with use of the medication. the potential for immune recall with imiquimod has been previously suggested based on studies showing higher rates of sustained field clearance. 2 one study by krawtchenko et al reported that 5% imiquimod cream produced significantly greater sustained total field clearance of ak at 12-months post treatment when compared to 5-fu and cryotherapy. 5 in a mouse model, hartwig et al showed imiquimod-induced clonal expansion of memory γδ t-cells, which persisted in both treated and untreated dermis long after initial treatment (6). second time use of imiquimod in these mice resulted in a robust and exaggerated inflammatory response. in this report, we present observations that arose from a quality improvement (qi) project initially designed to improve documentation of treatment response time in patients with actinic keratoses. our findings shed light onto whether the aforementioned phenomenon can be detected clinically in patients by comparing time-to-onset of clinical response in naïve and prior users of imiquimod for treatment of actinic keratoses. introduction skin may 2018 volume 2 issue 3 copyright 2018 the national society for cutaneous medicine 158 figure 1. imiquimod mechanism of action. imiquimod acts via agonism of toll-like receptor 7 (tlr7) and the nuclear factor kappa-b (nfκ-b) pathway, antagonism of toll-like receptor 8 (tlr8), the a2a receptor via adenylate cyclase (a precursor in the downstream hedgehog pathway), and the opioid growth factor receptor (ogfr). adapted from bozrova et al 2013. as part of a qi initiative performed in a private practice setting, a protocol of data collection was put in place for patients treated with 5% imiquimod cream for actinic keratoses of the head and neck. the goal of this data collection initiative was to determine factors leading to quicker onset of action and better outcomes that could be applied to future qi cycles. a total of 92 patients were included in this initiative. as per our standard protocol, patients were instructed to apply 5% imiquimod cream to the affected areas once daily until reaching a therapeutic endpoint of crusting/scabbing. patients received extensive instruction on medication use, supplemented with clinical photos of the desired endpoints of erythema and crusting/scabbing. the primary data points collected were time (days) to onset of erythema and time to onset of crusting/scabbing. results were selfreported, and all patients were evaluated in clinic at follow up in 14 days. patients were asked to send a clinical photo for methods skin may 2018 volume 2 issue 3 copyright 2018 the national society for cutaneous medicine 159 telemedicine review or to come to the clinic for evaluation if in doubt of whether they had reached the desired endpoint. when analyzing the results for qi purposes, an interesting observation regarding onset of clinical response in those who had been previously treated with imiquimod versus those who were imiquimod-naïve arose, and further analysis (stratifying results by these two treatment groups) was performed to investigate these findings more thoroughly. out of the 92 patients who took part in this project, there were 41 naïve users and 51 prior users of imiquimod. all patients reported adherence to the specified treatment regimen, and no unexpected adverse events were noted. the average time (days) to onset of erythema was 5.48 ± 3.19 days in naïve users and 4.7 ± 2.91 days in prior users (p= 0.22). average time to onset of crusting/scabbing was 9.2 ± 4.34 days in naïve users and 9.02 ± 3.65 days in prior users (p=0.35) (figure 2). there was no statistically significant difference between the two groups. figure 2. results. the average time (days) to onset of erythema was 5.48 ± 3.19 in naïve users and 4.7 ± 2.91 in prior users (p= 0.22). average time (days) to onset of crusting/scabbing was 9.2 ± 4.34 in naïve users and 9.02 ± 3.65 in prior users (p=0.35). results skin may 2018 volume 2 issue 3 copyright 2018 the national society for cutaneous medicine 160 imiquimod has been shown to act via a variety of complex mechanisms involving both innate and adaptive immunity. prior studies suggestive of higher sustained field clearance of ak with imiquimod, mouse studies showing activation of memory γδ t-cells, and numerous anecdotal reports from patients and physicians of faster onset of clinical response with second time use suggest the potential for immune recall. our study revealed there is no difference in time-toonset of erythema or scabbing/crusting with second-time use of imiquimod. while immune recall may be possible with use of imiquimod, the results of this study indicate that it may be independent of timeto-onset of clinical response. knowledge of time-to-onset of clinical response with use of imiquimod has significant clinical implications. it allows practitioners to appropriately set patient expectations for length of treatment course with initial and subsequent use. practitioners can also anticipate that the same quantity of medication may be required for each treatment course. while no difference in time-to-onset of clinical response was seen in this study, there is still evidence for higher sustained clearance of ak with use of imiquimod. with changing payment models and the potential for bundled reimbursement for clearance of ak, knowledge of which therapies achieve and sustain the highest degree of clearance may have financial implications in the future. 7 limitations of the study include the small sample size and the single clinical setting, in addition to the fact that our observations spawned from a qi project. moreover, only actinic keratoses were studied, and the selfreported nature of the primary outcomes is subject to recall bias. there is also potential for confounding factors given the observational nature of the study. conflict of interest disclosures: none funding: none corresponding author: stacy l. mcmurray, md university of tennessee health science center department of dermatology 930 madison avenue, suite 840 memphis, tn 38163 423-967-6710 (office) 423-967-6710 (fax) smcmurr4@uthsc.edu references: 1. exton, pa: graceway pharmaceuticals; 2008. aldara [package insert] 2. del rosso jq. the treatment of viral infections and nonmelanoma skin cancers. cutis. 2007;79(4 suppl):29–35. 3. yang x, dinehart m. triple hedgehog pathway inhibition for basal cell carcinoma. journal of clinical & aesthetic dermatology [serial online]. april 2017;10(4):47-49. available from: cinahl complete, ipswich, ma. accessed january 22, 2018. discussion skin may 2018 volume 2 issue 3 copyright 2018 the national society for cutaneous medicine 161 4. bozrova s, levitsky v, nedospasov s, et al. imiquimod: the biochemical mechanisms of immunomodulatory and antiinflammatory activity. biochemistry (moscow) supplement series b: biomedical chemistry [serial online]. april 1, 2013;7(2):136-145. available from: scopus®, ipswich, ma. accessed january 23, 2018. 5. krawtchenko n, roewert-huber j, ulrich m, et al. a randomised study of topical 5% imiquimod vs. topical 5-fluorouracil vs. cryosurgery in immunocompetent patients with actinic keratoses: a comparison of clinical and histological outcomes including 1-year followup. british journal of dermatology [serial online]. december 1, 2007;157(suppl. 2):34-40. available from: scopus®, ipswich, ma. accessed january 23, 2018. 6. hartwig t, pantelyushin s, croxford al, et al. dermal il-17-producing gammadelta t cells establish long-lived memory in the skin. eur j immunol. 2015;45(11):3022-33. 7. kirby j, miller j, delikat a, leslie d. bundled payment models for actinic keratosis management. jama dermatol [serial online]. n.d.;152(7):789-796. available from: science citation index, ipswich, ma. accessed january 22, 2018. acknowledgements: medical writing support was provided by prescott medical communications group (chicago, il) with financial support from ortho dermatologics; ortho dermatologics is a division of bausch health us, llc | 2020 fall clinical dermatology conference® for pas & nps • april 3-5, 2020 • orlando, fl synopsis ◾ onychomycosis—a chronic fungal nail infection—can occur in children, ranging in prevalence from 0.35% – 5.5% worldwide1 ◾ onychomycosis has been reported to be responsible for approximately 15% of all nail dystrophies in children2 ◾ treatment of onychomycosis is challenging, and can require systemic antifungals for prolonged periods of time; however, parents and healthcare practitioners are hesitant to use long-term systemic treatments in children3 ◾ efinaconazole 10% topical solution (jublia® ortho dermatologics, bridgewater, nj) is an azole antifungal indicated for the topical treatment of onychomycosis of the toenails due to trichophyton rubrum and trichophyton mentagrophytes objective ◾ to evaluate efinaconazole 10% topical solution in pediatric patients with onychomycosis methods ◾ this phase 4, multicenter, open-label study evaluated safety, pharmacokinetics (pk), and efficacy of efinaconazole 10% topical solution in pediatric patients with distal lateral subungual onychomycosis ◾ efinaconazole was administered once daily for 48 weeks, with a 4-week posttreatment follow up at week 52 ◾ participants were aged 6 – 16 years with culture-positive mild-to-severe onychomycosis affecting ≥20% of at least 1 great toenail ◾ the pk subset was patients 12 – 16 years with moderate-to-severe onychomycosis affecting ≥50% of each great toenail and onychomycosis in ≥4 additional toenails ◾ the primary objective of this study was evaluation of safety and pk • safety included adverse events (aes) and serious aes (saes) • pk assessments included area under the concentration time curve from 0 to 24 hours (auc0 -24 ), maximum plasma concentration (cmax ), and time to cmax (tmax ); pk parameters were assessed based on blood samples collected on days 28 and 29 (predose and up to 24 hours postdose) ◾ efficacy assessments included mycologic cure, complete cure, and clinical efficacy safety, pharmacokinetics, and efficacy of efinaconazole 10% topical solution for the treatment of onychomycosis in pediatric patients pharmacokinetics ◾ the final pk analysis population comprised 15 patients; 2 patients were not included (samples arrived thawed from facility [n=1] and statistical outlier [n=1]) ◾ the concentration-time profiles for efinaconazole and the h3 metabolite were relatively stable, with only minor fluctuations during the 24-hour dosing interval (figure 1) ◾ systemic exposure to efinaconazole was low (table 2) ◾ based on mean auc0-24 in molar amounts, exposure to the h3 metabolite was approximately 5-fold higher than that observed for efinaconazole (0.169 versus 0.0327 nmol*h/ml) figure 1. mean efinaconazole and h3 metabolite plasma concentration-time profiles after topical administration of efinaconazole solution on day 28 (pk analysis population) 2.00 1.75 1.50 1.25 1.00 0.75 0.50 0.25 0m e a n p la sm a c o n ce n tr a ti o n ( n g /m l) time (hours) 0 2 4 12 24 e�naconazole (n=15) h3 metabolite (n=15) table 2. mean pharmacokinetic parameters of efinaconazole and h3 metabolite after topical administration of efinaconazole solution on day 28 (pk analysis population) efinaconazole (n=15) h3 metabolite (n=15) tmax , median (range), h 12.0 (0.00 – 24.5) 4.05 (0.00 – 24.5) cmax , mean (sd), ng/ml 0.549 (0.375) 1.65 (1.31) auc0-24, mean (sd), ng*h/ml 11.4 (7.68)a 38.1 (30.4)b an=11; bn=13. auc0-24 , area under the concentration time curve from 0 to 24 hours; cmax , maximum plasma concentration; sd, standard deviation; tmax , time to maximum plasma concentration. efficacy ◾ by week 52, 65.0% of patients achieved mycologic cure, with a 36.7% mycologic cure rate observed as early as week 12 (figure 2) ◾ a total of 40.0% of patients had complete cure by week 52 (figure 3), and half of patients achieved clinical efficacy by study end (figure 4) figure 2. mycologic cure (safety population, locf) 0% 25% 50% 75% 100% 0 12 24 36 48 52 p e rc e n ta g e o f p a rt ic ip a n ts study visit (weeks) e�naconazole 10% (n=60) 0% 36.7% 70.0% 70.0% 65.0% 53.3% mycologic cure was defined as negative potassium hydroxide (koh) and negative fungal culture. locf, last observation carried forward. figure 3. complete cure (safety population, locf) 0% 25% 50% 75% 100% 0 12 24 36 48 52 p e rc e n ta g e o f p a rt ic ip a n ts study visit (weeks) e�naconazole 10% (n=60) 0% 0% 8.3% 35.0% 40.0% 0% complete cure was defined as 0% clinical involvement of the target toenail and mycologic cure (negative koh and negative fungal culture). locf, last observation carried forward. figure 4. clinical efficacy (safety population, locf) 0% 25% 50% 75% 100% 0 12 24 36 48 52 p e rc e n ta g e o f p a rt ic ip a n ts study visit (weeks) e�naconazole 10% (n=60) 0% 0% 18.3% 43.3% 50.0% 8.3% clinical efficacy was defined as affected target great toenail area <10%. locf, last observation carried forward. conclusions ◾ efinaconazole 10% topical solution administered once daily for a year was well tolerated in this pediatric population ◾ the systemic exposure to efinaconazole in this pediatric population was comparable to that previously reported in adults (cmax , 0.67 ng/ml; auc0-24 , 12.15 ng*h/ml)4 ◾ efinaconazole was efficacious in pediatric patients, with improved mycologic cure (65%) and complete cure (40%) rates compared with adults from two 1-year studies (mycologic cure: 53.4–55.2%; complete cure: 15.2–17.8%)4 references 1. gupta ak, et al. pediatr dermatol. 2018;35(5):552-559. 2. rodriguez-pazos l, et al. mycoses. 2011;54(5):450-453. 3. eichenfield lf, friedlander sf. j drugs dermatol. 2017;16(2):105-109. 4. prescribing information. jublia® (efinaconazole) topical solution, 10%. ortho dermatologics. author disclosures le has served as investigator and consultant for ortho dermatologics. be has provided clinical research support (research funding to university) for abbvie, anaptysbio, boehringer ingelheim, bristol myers squibb, celgene, incyte, leo, lilly, merck, menlo, novartis, pfizer, regeneron sun, ortho dermatologics, vanda; and as consultant (received honorarium) from boehringer ingelheim, celgene, leo, lilly, menlo, novartis, pfizer, sun, ortho dermatologics, verrica. js is a consultant for ortho dermatologics, bausch health, regeneron, sanofi, and pfizer. tr has served as consultant for ortho dermatologics. ag has served as consultant, speaker, and investigator for ortho dermatologics. wc has nothing to disclose. rp is an employee of bausch health us, llc and may hold stock and/or stock options in its parent company. aj is an employee of ortho dermatologics and may hold stock and/or stock options in its parent company. results study population ◾ a total of 62 patients were enrolled in the study; of these, 12 (19.4%) patients did not complete the study (withdrawal by parent/guardian, n=6; lost to follow-up, n=5; participant request, n=1) ◾ sixty participants administered ≥1 dose of study drug (safety population), 17 of whom had pk data on days 28 and 29 (pk population) ◾ in the safety population, mean age was 13.4 years (range: 6 – 16 years), 66.7% were male, and 88.3% were white ◾ in the pk population, mean age was 14.1 years (range: 12 – 16 years), 64.7% were male, and 100% were white safety ◾ a summary of all treatment-emergent aes (teaes) is shown in table 1 ◾ all teaes were mild or moderate and none led to study discontinuation ◾ the only treatment-related teae was ingrowing nail, with 8 events in 2 participants (table 1) ◾ no treatment-related saes were reported ◾ no safety signals or trends associated with local skin reactions were observed table 1. treatment-emergent adverse event summary (safety population) efinaconazole solution (n=60) number of teaes, no. 99 participants with ≥1 teae, n (%) 38 (63.3) participants with ≥1 treatment-emergent sae, n (%) 1 (1.7)a most common teaes (>5% in safety population), n (%) nasopharyngitis 18 (30.0) headache 6 (10.0) influenza 5 (8.3) tinea pedis 4 (6.7) contusion 4 (6.7) nail injury 4 (6.7) ingrowing nail 4 (6.7) treatment-related teae, n (%) ingrowing nail 2 (3.3) athe sae of pneumonia was deemed unrelated to treatment; the moderate event resolved with hospitalization and did not require a change in study drug application. sae, serious adverse event, teae, treatment-emergent adverse event. lawrence f eichenfield, md1; boni elewski, md2; jeffrey l sugarman, md, phd3; ted rosen, md4; aditya gupta, md, phd5; wendy cantrell, dnp, crnp6; radhakrishnan pillai, phd7; abby jacobson, ms, pa-c8 1departments of dermatology and pediatrics; university of california, san diego school of medicine and rady children’s hospital, san diego, ca; 2university of alabama at birmingham school of medicine, birmingham, al; 3university of california, san francisco, ca; 4baylor college of medicine, houston, tx; 5mediprobe research inc., london, on, can and university of toronto, toronto, on, can; 6village dermatology, birmingham, al; 7bausch health us, llc*, petaluma, ca; 8ortho dermatologics*, bridgewater, nj *bausch health us, llc is an affiliate of bausch health companies inc. ortho dermatologics is a division of bausch health us, llc. skin september 2017 volume 1 issue 2 copyright 2017 the national society for cutaneous medicine 100 brief articles hailey-hailey disease complicated by herpes simplex viral infection morgan arnold, b.s. a , mai-anh vu, b.s. a , emily grimshaw, m.d. b and michael wilkerson, m.s., m.d. b a university of texas medical branch at galveston school of medicine b university of texas medical branch at galveston department of dermatology eczema herpeticum refers to a disseminated hsv infection in areas of impaired skin barrier, most commonly in the setting of atopic dermatitis. it has rarely been reported in the literature in hailey-hailey disease patients. when recognized early, eczema herpeticum is easily and effectively treated with antiviral medications. a 51-year-old man with a history of haileyhailey disease and recurrent mrsa cutaneous infections presented with a rash in his groin persisting for two weeks. this flare was more painful than usual and felt “like ants under (his) skin”. he had been treated without improvement at an outside facility for presumed staphylococcal and yeast infections with low-dose prednisone, iv daptomycin, and topical nystatin. gold bond powder was also unhelpful. on physical exam, macerated erythematous thin plaques were present with superimposed grouped punched-out ulcers in the inguinal folds and on the scrotum. there were also crusted small red papules scattered over the central chest, upper back, axillary vaults and posterior neck. biopsy from the upper back showed extensive suprabasal acantholysis consistent with hailey-hailey disease. secondary infection in the groin with herpes simplex virus (hsv) was suspected; a viral culture from the abstract a 51-year-old man with a history of hailey-hailey disease presented to clinic due to worsening discomfort from a rash in his groin. physical examination of the inguinal area and scrotum revealed grouped, punched -out ulcers on a base of macerated, erythematous plaques. viral culture from the ulcers was positive for hsv -2. the patient had no known history of herpesvirus infection. treatment with oral valacyclovir resulted in marked clinical improvement. although cases of hailey hailey herpeticum are much less common than the better-studied eczema herpeticum, it is important for physicians to be aware that any disease that disrupts the stratum corneum increases the risk of superimposed hsv infection, which constitutes a medical emergency. prompt treatment with antiviral agents can hasten patient recovery and optimize outcomes. introduction case presentation skin september 2017 volume 1 issue 2 copyright 2017 the national society for cutaneous medicine 101 inguinal ulcers was positive for hsv type 2. a pemphigus antibody panel was negative and cbc showed mild leukocytosis. the patient denied a history of genital or oral ulcers and had no known history of hsv infection. the patient experienced significant improvement with oral valacyclovir. figures figure 1: crusted erythematous papules scattered over the central chest. figure 3: h&e (40x). suprabasal acantholysis throughout the epidermis consistent with haileyhailey disease figure 2: macerated erythematous thin plaques with superimposed crusted punched-out ulcers in the inguinal fold and scrotum. skin september 2017 volume 1 issue 2 copyright 2017 the national society for cutaneous medicine 102 eczema herpeticum (eh), also known as kaposi varicelliform eruption, was initially described by kaposi in 1887, who thought it resembled chickenpox 1 . eh is the dissemination of a viral infection in the setting of a preexisting skin disease. haileyhailey disease, also known as familial benign pemphigus, is a chronic autosomal dominant blistering dermatosis which usually presents around the third or fourth decades. the disease is a rare genetic disorder that is caused by a lack of protein hspca1 produced by gene atp2c1 located on chromosome 3. this protein is essential for the proper health of skin. the lack of the normal protein causes cells of the skin not to adhere together properly due to malformation of intercellular desmosomes. patients with such disease will develop blisters and erosions most often affecting the neck, armpits, skin folds and genitals. eh in the setting of hailey-hailey disease is an uncommon occurrence and only a handful of cases have been reported in the literature 2,3 . most cases of eh are due to herpes simplex virus type 1 or 2. other viruses may rarely be responsible, such as coxsackievirus a16 1 . this potentially fatal infection appears in areas of compromised skin barrier, including those affected by atopic and contact dermatitis, thermal burns, pemphigus, darier disease, cutaneous t cell lymphoma, seborrheic dermatitis, and hailey-hailey disease among others 2,3 . it usually begins as clusters of vesiculopustules on affected skin and may be accompanied by flu-like symptoms such as fever, chills, and malaise. eh can progress to have severe sequelae, such as herpes keratitis, secondary bacterial infection, disseminated infection with multiorgan involvement, and death, with mortality ranging from 1 to 9 percent 4 . diagnostic methods of herpes infection include viral culture, direct fluorescent antibody staining, skin biopsy, tzanck smear exhibiting epithelial multinucleated giant cells and acantholysis, and polymerase chain reaction 1,2,3,5 . early initiation of antiviral therapy in suspected cases should not be delayed while awaiting test results. the nucleoside analogs, which inhibit viral dna polymerase, are most commonly used and are very effective 4 as was seen in our patient. eczema herpeticum can be life-threatening and is considered a dermatologic emergency 4,6 . this case demonstrates the importance for physicians to consider superinfection with herpes in patients with a breakdown of skin barrier, especially in particularly painful and treatment-resistant flares of their skin disease. early recognition and treatment of eczema herpeticum with an antiviral can rapidly mitigate the morbidity associated with the infection. conflict of interest disclosures: none. funding: none. corresponding author: michael wilkerson, md 301 university blvd. 4. 112 mccullough bldg galveston, texas 77555-0783 phone: (409) 772 1911 email: mgwilker@utmb.edu references: 1. lin cy. “eczema herpeticum.” dermnet nz. dermnet new zealand trust. 1996. web. 10 apr 2016. conclusion discussion skin september 2017 volume 1 issue 2 copyright 2017 the national society for cutaneous medicine 103 2. de aquino paulo filho t, defreitas ykr, da nóbrega mta, et al. “hailey-hailey disease associated with herpetic eczema—the value of the tzanck smear test.” dermatology practical & conceptual. 2014;4(4):29-31. 3. lee gh, kim ym, lee sy, lee js, park yl, whang ku. “a case of eczema herpeticum with hailey-hailey disease.” annals of dermatology. 2009;21(3):311-314. 4. olson j, robles dt, kirby p, colven r. “kaposi varicelliform eruption (eczema herpeticum).” dermatol online journal. 2008 feb 28;14(2):18. 5. schirren h, schirren cg, schlupen em, volkenandt m, kind p. “exacerbation of hailey-hailey disease by infection with herpes simplex virus. detection with polymerase chain reaction.” hautarzt. 1995;46:494–497. 6. mackley cl, adams dr, anderson b, miller jj. “eczema herpeticum: a dermatologic emergency.” dermatol nurs. 2002 oct;14(5):307-10, 323. powerpoint presentation david m. pariser1, lawrence j. green2, edward l. lain3, jodi l. johnson4, ayman grada5 1eastern virginia medical school and virginia clinical research, inc., norfolk, va, usa; 2george washington university school of medicine, washington, dc, usa; 3austin institute for clinical research, pflugerville, tx, usa; 4departments of dermatology and pathology, feinberg school of medicine, northwestern university, usa, 5r&d and medical affairs, almirall (us), exton, pennsylvania, usa. email: grada@bu.edu introduction methods results conclusion long-term safety and tolerability of sarecycline for the treatment of acne vulgaris: results from a phase iii, multicenter, open-label study and a phase i phototoxicity study  sarecycline is a narrow-spectrum tetracycline-class antibiotic designed for the treatment of moderate-to-severe acne.  sarecycline’s narrow-spectrum anti-bacterial activity and lipophilicity may minimize side effects commonly associated with broad-spectrum tetracyclines, such as minocycline and doxycycline.  here, we report the results of 2 identically designed, phase 3 pivotal trials, sc1401 and sc1402, to evaluate the efficacy and safety of oncedaily sarecycline (n=2002). • sarecycline was associated with low rates of teaes, with nasopharyngitis, upper-respiratory-tract infection, headache, and nausea being the only teaes reported ≥2% or more of patients with moderate-to-severe acne vulgaris aged nine years or older treated with sarecycline once daily for up to 40 weeks. • rates of teaes commonly associated with other tetracycline antibiotics were for dizziness (0.4%) and sunburn (0.2%), and for gastrointestinal teaes, nausea (2.1%), vomiting (1.9%), and diarrhea (1.0%). vulvovaginal mycotic infection (0.8%). • sarecycline has low potential to cause clinically significant phototoxicity • no clinically meaningful safety findings were noted.  patients (n=483) aged 9 years or older with moderate-to-severe acne who completed one of two prior pivotal phase iii, double-blind, placebo-controlled, 12week trials in which they received sarecycline 1.5mg/kg/day or placebo once daily were continued on once daily sarecycline for up to 40 weeks study visits: weeks 2, 6, 12,18, 24, 32 and 40  excluded: receiving/planning to receive any systemic acne vulgaris medication, systemic retinoids, systemic corticosteroids or any androgen/anti-androgenic therapy (e.g. testosterone, spironolactone)  included: allowed use of topical acne vulgaris medications  the primary assessment was the safety of sarecycline 1.5mg/kg/day for 40 weeks as indicated by adverse events (aes), vital signs, electrocardiograms, clinical laboratory tests, and physical examinations.  patterns of sarecycline use were a secondary assessment.  subjects treated until adequate improvement obtained as per investigator judgment (eg, iga score of 0 or 1) and re-initiated if acne recurred (eg, iga score ≥ 3) phase-3 long-term safety (40-week) synopsis pariser dm, green lj, lain el, schmitz c, chinigo as, mcnamee b, berk dr. safety and tolerability of sarecycline for the treatment of acne vulgaris: results from a phase iii, multicenter, open-label study and a phase i phototoxicity study. the journal of clinical and aesthetic dermatology. 2019 nov;12(11):e53.  19 subjects (healthy; non-smoker, men, aged 18 to 45 years) received placebo or 240mg of sarecycline in a random order in each of the two treatment periods (not weight based)  a two-treatment, two-period, two-sequence crossover design. treatment periods were separated by at least nine days  at three hours after administration of the study treatment, a previously unexposed area of each subject’s back was irradiated with 16j/cm2 of uva, after which point, another area was irradiated with uva/uvb at 50 percent of the subject’s minimum erythemal dose (med)  uv-exposed skin was assessed visually at 24, 48, and 72 hours after irradiation, and uv-induced skin reaction was evaluated using dermal response score scale  mean and maximum numerical uv-induced dermal response scores were determined for sarecycline and placebo phase-1 phototoxicity teaes of interest safety population placebo/sarecycline (n=236), n (%) sarecycline/sarecycline (n=247), n (%) total (n=483), n (%) common teaes (≥2% of patients in either group) nasopharyngitis 13 (5.5) 5 (2.0) 18 (3.7) upper-respiratory-tract infection 7 (3.0) 9 (3.6) 16 (3.3) headache 9 (3.8) 5 (2.0)b 14 (2.9)b urinary tract infection 2 (0.8) 5 (2.0) 7 (1.4) gastrointestinal nausea 4(1.7) 6(2.4) 10(2.1) vomiting 3(1.3) 6(2.4) 9(1.9) diarrhea 3 (1.3) 2 (0.8) 5 (1.0) constipation 2 (0.8) 0 2 (0.4) vestibular dizziness 1(0.4) 1(0.4) 2(0.4) vertigo 0 0 0 tinnitus 0 0 0 sunburn and skin hyperpigmentation sunburn 0 1(0.4) 1(0.2) skin hyperpigmentation 1(0.4) 0 1(0.2) vaginal yeast infections in females vulvovaginal mycotic infection 0 2(1.6) 2(0.8) genital fungal infection 0 1(0.4) 1(0.2) genital candidiasis 1(0.4) 0 1(0.2) results: dermal response to uv exposure did not exceed mild erythema with either sarecycline or placebo at any time point, and the mean and maximum uvinduced dermal response scores for both sarecycline and placebo were low. no teaes or serious aes were reported in the phototoxicity study the safety population included 483 patients; 354 patients (73.3%) completed the study 1 mailto:grada@bu.edu https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6937166/ slide number 1 efficacy of tapinarof cream by body region in subjects with plaque psoriasis in a phase 2b randomized controlled study robert bissonnette md msc,1 linda stein gold md,2 leon kircik md,3,4 stephen tyring md phd mba,5 anna m tallman pharmd,6 april armstrong md mph7 1innovaderm research inc., montreal, qc, canada; 2henry ford health system, detroit, mi, usa; 3skin sciences pllc, louisville, ky, usa; 4icahn school of medicine at mount sinai, new york, ny, usa; 5the university of texas health science center, houston, tx, usa; 6dermavant sciences, inc., long beach, ca, usa; 7keck school of medicine of the university of southern california, los angeles, ca, usa introduction ■ psoriasis is a chronic, immune-mediated disease characterized by scaly, erythematous, and pruritic plaques that can be painful and disfiguring1 ■ plaque localization can impact quality of life, and response to treatment may also vary by body region2 ■ although multiple options are available for the treatment of plaque psoriasis, there is a need for effective topical therapies that can be used without body surface area (bsa) restrictions or concerns for the duration of treatment ■ tapinarof is a therapeutic aryl hydrocarbon receptor modulating agent (tama) under investigation for the treatment of psoriasis (nct03956355 & nct03983980) and atopic dermatitis ■ this previously conducted phase 2b dose-finding study (nct02564042) was designed to assess the efficacy and safety of tapinarof cream in subjects with plaque psoriasis3,4 ■ this analysis was conducted to explore whether the efficacy and safety of tapinarof varied across body regions objectives ■ to report efficacy outcomes by mean change in psoriasis area and severity index (pasi) from baseline, overall and by body region methods study design ■ in this multicenter (united states, canada, and japan), phase 2b, double-blind, vehicle-controlled, randomized study, adult subjects with psoriasis were randomized 1:1:1:1:1:1 to receive tapinarof cream 0.5% or 1% once (qd) or twice daily (bid) or vehicle qd or bid for 12 weeks and followed up for 4 more weeks (figure 1) figure 1. study design tapinarof 1% bid (n=38) tapinarof 1% qd (n=38) tapinarof 0.5% bid (n=38) tapinarof 0.5% qd (n=38) vehicle bid (n=37) vehicle qd (n=38) offtreatment adult subjects with stable plaque psoriasis for ≥6 months • aged 18–65 years • bsa ≥1%–≤15%* • pga ≥2 (n=227) r double-blind treatment (12 weeks) follow-up (4 weeks) *excluding scalp. bid, twice daily; bsa, body surface area; pga, physician global assessment; qd, once daily; r, randomized. study outcomes and statistical analysis ■ the primary endpoint was physician global assessment (pga) response rate at week 12, defined as the proportion of subjects with a pga score of clear (0) or almost clear (1) and ≥2-grade improvement in pga score from baseline to week 123 ■ additional post-hoc efficacy analyses reported here include mean change in pasi from baseline overall and by body region (upper extremities, lower extremities, head/neck, and trunk) ■ incidence, frequency, and nature of adverse events (aes) and serious aes were collected from the start of study treatment until the end-of-study visit at week 16 results subject disposition ■ a total of 227 subjects (of 290 screened) were randomized (intent-to-treat population), and of those randomized, 175 subjects (77%) completed the study, including the week 16 follow-up visit baseline characteristics ■ mean demographic and baseline characteristics were comparable across groups (table 1) ■ mean pasi score at baseline was 8.8 (standard deviation 4.5) ■ pga category at baseline: – 15% had a pga of 2 (mild) – 80% had a pga of 3 (moderate) – 5% had a pga of 4 (severe) table 1. baseline subject demographics and characteristics tapinarof cream 1% tapinarof cream 0.5% vehicle bid (n=38) qd (n=38) bid (n=38) qd (n=38) bid (n=37) qd (n=38) mean age, years (sd) 45.9 (11.9) 48.5 (10.6) 49.6 (10.9) 48.7 (9.7) 46.7 (12.6) 46.4 (10.2) male sex, n (%) 26 (68) 26 (68) 24 (63) 25 (66) 23 (62) 29 (76) mean weight, kg (sd) 85.6 (22.5) 86.7 (22.6) 88.6 (27.4) 89.3 (23.1) 87.8 (28.3) 91.6 (21.6) pga, mean (sd) 2.9 (0.4) 2.7 (0.5) 3.0 (0.5) 2.9 (0.4) 3.0 (0.3) 2.8 (0.4) pasi, mean (sd) 10.6 (5.0) 8.5 (3.6) 8.2 (4.5) 7.9 (4.8) 9.0 (4.3) 8.7 (4.4) % bsa affected, mean (sd) 8.2 (4.5) 6.5 (3.3) 7.2 (4.5) 6.1 (4.3) 6.6 (3.6) 7.0 (4.6) pruritus score, mean (sd)* 5.6 (2.6) 4.4 (2.9) 6.2 (2.2) 4.5 (2.6) 5.5 (2.8) 4.9 (2.4) characteristics provided for the mitt population (n=196), which included subjects in the itt population minus the subjects from one site due to protocol violation. demographics (age, sex, and weight) provided for the safety population (n=227). *mean scores based on a numeric rating scale of 0 ‘absent’ to 10 ‘worst imaginable’; data provided for subjects with available results (n=32, 35, 30, 32, 29, and 32, respectively). bid, twice daily; bsa, body surface area; itt, intent-to-treat; mitt, modified intent-to-treat; pasi, psoriasis area and severity index; pga, physician global assessment; qd, once daily; sd, standard deviation. pga response rates ■ primary endpoint: pga response rates (defined as pga score 0 or 1 and ≥2-grade improvement) at week 12 were significantly higher (at 0.05 significance level) in the tapinarof cream groups than the vehicle groups (65% [1% bid], 56% [1% qd], 46% [0.5% bid], and 36% [0.5% qd] vs 11% [vehicle bid] and 5% [vehicle qd]) and were maintained for 4 weeks after the end-of-study treatment in all active treatment groups, except for the 0.5% bid group3 mean change in pasi ■ mean pasi improvements at week 12 were significantly greater in all tapinarof groups vs vehicle groups (all p<0.001): –8.70 (1% bid), –6.62 (1% qd), –6.30 (0.5% bid), and –5.41 (0.5% qd) vs –2.77 (vehicle bid) and –1.54 (vehicle qd); significant improvements were maintained in all tapinarof groups for 4 weeks after the last application through week 16 (figure 2) figure 2. mean change in pasi from baseline n=23 n=25 n=26 n=28 n=19 n=20 *** *** *** *** n=24 n=26 n=26 n=28 n=19 n=19 *** *** ** *** m e a n c h a n g e i n p a s i -6 0 -12 week 12 week 16 (end-of-treatment follow-up) tapinarof 1% bid tapinarof 1% qd tapinarof 0.5% bid tapinarof 0.5% qd vehicle bid vehicle qd n is number of subjects with available results at weeks 12 and 16. difference vs vehicle was statistically significant at **p<0.01, ***p<0.001. bid, twice daily; pasi, psoriasis area and severity index; qd, once daily. mean change in pasi by body region ■ upper extremities: mean pasi improvements in the upper extremities at week 12 were significantly greater in all tapinarof groups vs vehicle groups: –9.65 (1% bid; p=0.001), –9.05 (1% qd; p<0.001), –8.70 (0.5% bid; p=0.011), and –6.04 (0.5% qd; p<0.001) vs –4.88 (vehicle bid) and –1.61 (vehicle qd); significant improvements were maintained in all tapinarof groups for 4 weeks after the last application through week 16 (figure 3) figure 3. mean change in pasi from baseline in the upper extremities n=23 n=21 n=23 n=24 n=17 n=18 ** *** * *** n=24 n=22 n=23 n=26 n=17 n=17 ** *** * *** m e a n c h a n g e i n p a s i -6 0 -12 week 12 week 16 (end-of-treatment follow-up) tapinarof 1% bid tapinarof 1% qd tapinarof 0.5% bid tapinarof 0.5% qd vehicle bid vehicle qd n is number of subjects with available results at weeks 12 and 16. difference vs vehicle was statistically significant at *p<0.05, **p<0.01, ***p<0.001. bid, twice daily; pasi, psoriasis area and severity index; qd, once daily. ■ lower extremities: mean pasi improvements in the lower extremities at week 12 were significantly greater in all tapinarof groups vs vehicle groups (all p<0.001): –8.74 (1% bid), –8.19 (1% qd), –7.16 (0.5% bid), and –6.33 (0.5% qd) vs –2.47 (vehicle bid) and –2.0 (vehicle qd); significant improvements were maintained in all tapinarof groups for 4 weeks after the last application through week 16 (figure 4) figure 4. mean change in pasi from baseline in the lower extremities n=23 n=21 n=25 n=27 n=19 n=19 *** *** *** *** n=24 n=22 n=25 n=27 n=19 n=18 *** *** *** *** -6 0 -12 m e a n c h a n g e i n p a s i week 12 week 16 (end-of-treatment follow-up) tapinarof 1% bid tapinarof 1% qd tapinarof 0.5% bid tapinarof 0.5% qd vehicle bid vehicle qd n is number of subjects with available results at weeks 12 and 16. difference vs vehicle was statistically significant at ***p<0.001. bid, twice daily; pasi, psoriasis area and severity index; qd, once daily. ■ head/neck: mean pasi improvements in the head/neck at week 12 were significantly greater in all tapinarof groups vs vehicle groups, except for the 0.5% bid group: –9.0 (1% bid; p= 0.023), –7.40 (1% qd; p= 0.019), –5.0 (0.5% bid; p= 0.149), and –9.0 (0.5% qd; p= 0.007) vs –1.75 (vehicle bid) and –2.5 (vehicle qd); significant improvements were maintained in the 1% tapinarof groups for 4 weeks after the last application through week 16 (figure 5) figure 5. mean change in pasi from baseline in the head/neck n=16 n=20 n=18 n=16 n=8 n=10 * * ** n=18 n=22 n=19 n=17 n=8 n=9 * * -6 0 -12 m e a n c h a n g e i n p a s i week 12 week 16 (end-of-treatment follow-up) tapinarof 1% bid tapinarof 1% qd tapinarof 0.5% bid tapinarof 0.5% qd vehicle bid vehicle qd n is number of subjects with available results at weeks 12 and 16. difference vs vehicle was statistically significant at *p<0.05, **p<0.01. bid, twice daily; pasi, psoriasis area and severity index; qd, once daily. ■ trunk: mean pasi improvements in the trunk at week 12 were significantly greater in all tapinarof groups vs vehicle groups, except for the 0.5% bid group: –11.94 (1% bid; p<0.001), –9.13 (1% qd; p<0.001), –9.0 (0.5% bid; p= 0.052), and –8.25 (0.5% qd; p= 0.001) vs –4.08 (vehicle bid) and –1.85 (vehicle qd); significant improvements were maintained in all tapinarof groups, except for 0.5% bid, for 4 weeks after the last application through week 16 (figure 6) figure 6. mean change in pasi from baseline in the trunk n=17 n=16 n=16 n=16 n=13 n=13 *** *** ** n=18 n=17 n=17 n=17 n=13 n=14 * *** ** week 12 week 16 (end-of-treatment follow-up) -6 0 -12 m e a n c h a n g e i n p a s i n is number of subjects with available results at weeks 12 and 16. difference vs vehicle was statistically significant at *p<0.05, **p<0.01, ***p<0.001. bid, twice daily; pasi, psoriasis area and severity index; qd, once daily. safety ■ tapinarof cream was generally well tolerated3 ■ treatment-emergent aes (teaes) were mostly mild to moderate in severity ■ the most common treatment-related teaes were folliculitis (10% tapinarof vs 1% vehicle), contact dermatitis (3%; all tapinarof), and headache (1%; all tapinarof) conclusions ■ tapinarof cream demonstrated consistent and durable efficacy across body regions as measured by mean change in pasi from baseline to week 12, which was maintained for 4 weeks after last application of study treatment ■ these findings support previously reported efficacy and safety outcomes3,4 ■ a phase 3 clinical trial program of tapinarof cream 1% qd in psoriasis, consisting of two studies psoaring 1 (nct03956355) and psoaring 2 (nct03983980) has completed. the long-term extension study psoaring 3 (nct04053387) is ongoing references 1. menter a et al. j am acad dermatol. 2008;58:829–850. 2. dopytalska k et al. reumatologia. 2018;56:392–398. 3. robbins k et al. j am acad dermatol. 2019;80:714–721. 4. stein gold l et al. j am acad dermatol. 2020. doi: 10.1016/j.jaad.2020.04.181. acknowledgments the authors thank the participating investigators, patients and their families, and colleagues involved in the conduct of the study. editorial and medical writing support under the guidance of the authors was provided by apothecom, uk, and was funded by dermavant sciences, inc. in accordance with good publication practice (gpp3) guidelines (ann intern med. 2015;163:461–464). contact dr robert bissonnette at rbissonnette@innovaderm.com with questions or comments. figure 2. a) inter-assay correlation analysis for 168 cases; b) blandaltman plot for 168 cases showing estimated bias (mean difference in discriminant scores, red line) and 95% confidence interval (dashed lines); c) instrument-to-instrument correlation analysis for 21 cases; d) blandaltman plot for 21 cases showing estimated bias (mean difference in discriminant scores, red line) and 95% confidence interval (dashed lines) background • the majority of metastases and death attributed to cutaneous melanoma (cm) occur in patients who are initially diagnosed with stage i or stage ii disease.1 • a 31-gene expression profile (gep) test that provides a molecular classification associated with risk of metastasis has been validated and clinically available since 2013.2,3 • the test determines a low risk (class 1) or high risk (class 2) of metastasis within five years of the primary diagnosis of cm with an area of reduced confidence identified from the true positives and negatives from the training set. • this study evaluated the analytical reliability and reproducibility of the 31-gep test • we also report the technical experience of the test and the association of risk prediction with standard clinicopathologic factors linked to cm metastasis and death. methods • formalin-fixed paraffin-embedded tissue from primary melanoma tumors was successfully processed for 8,244 patients from 1,123 centers in the u.s. and spain between march 2013 and june 2016 using the 31-gep rt-pcr-based assay. • metastatic risk class was determined using a proprietary predictive modeling algorithm which provides two results: a binary classification of class 1 (low risk) or class 2 (high-risk) tumor biology, and a quantitative discriminant score from 0 to 1.0, for which 0.5 represents the cutoff score between the binary classes. • testing was repeated for a subset of the specimens to assess interassay variability and concordance of risk assignment. • quality control and multiple gene failures were assessed, and pathology reports were evaluated for all specimens to evaluate association of the test results with clinical and pathologic characteristics of the samples. table 2. pathologic characteristics of all successfully reported samples according to gep class result; stage iib and above, breslow >1mm, ulceration, and mitotic rate ≥1/mm2 were significantly associated with class result (fisher’s exact test, p<0.0001) results conclusions • the 31-gep test demonstrates robust, reproducible and reliable performance in primary tumor ffpe specimens. • educational efforts in biopsy tissue conservation practices have yielded significant improvements in the rate of tissue received with adequate tumor nuclei content. • though high-risk (class 2) molecular classification is associated with pathologic stage and other prognostic factors, a significant number of metastatic cases classified as low risk by anatomic staging are identified by the gep.2,3 references 1. morton dl, et al. n engl j med 2014;370:599-609. 2. gerami p, et al. clin cancer res 2015;21:175-83. 3. gerami p, et al. j am acad dermatol 2015;72:780-5 e783. disclosures the proprietary gep test is clinically available through castle biosciences as the decisiondx®-melanoma test (www.skinmelanoma.com). clinical reliability and reproducibility of a prognostic 31-gene expression profile test for cutaneous melanoma, and association of the test with standard clinicopathologic factors robert w. cook, phd, kristen oelschlager, rn, trisha poteet, derek maetzold, john stone, phd, federico monzon, phd castle biosciences, inc., friendswood, tx, us figure 3. discriminant scores for a single class 1 tumor control sample across 47 experiments figure 5. example of ‘educational tool’ that was developed to encourage tumor tissue preservation as well as to sensitize to tumor density analysis table 1. overview of technical reproducibility studies study design concordance r2 value inter-assay 168 samples run on two separate days 99.4% 0.96 instrument-toinstrument 21 samples run on two machines 95% 0.85 inter-operator 268 samples run by two personnel 100% 1.0 inter-assay, instrument-toinstrument, and intra-operator reliability 0.0 0.5 1.0 discriminant score march 1, 2013 – december 31, 2015 january 1, 2016 – june 30, 2016 reduction in required tumor content from >60% to >40% and improvements in biopsy tissue preservation figure 4. technical experience of the 31-gep test for samples submitted from march 2013 to june 2016 figure 1. workflow schematic of the 31-gep test class 1 (%) n = 5,594 class 2 (%) n = 1,301 breslow thickness, mm 0-1.00 (thin) 71% 12% 1.01-4.00 (intermediate) 27% 68% >4.01 (thick) 1% 19% unknown 1% 1% ulceration absent 89% 47% present 7% 48% unknown 4% 5% mitotic rate <1/mm2 39% 7% ≥1/mm2 40% 73% unknown 21% 20% ajcc stage 0 0.1% 0% i 79% 25% ii 9% 63% iii 0.4% 1% unknown 11% 11% a b c d fc17postercastlebiosciencescookclinicalreliability.pdf skin may 2018 volume 2 issue 3 copyright 2018 the national society for cutaneous medicine 202 brief articles mycobacterium marinum infection in a post-katrina carpenter: the importance of exposures zachary p. nahmias md a , tina hsu ba b , c. brad bledsoe md c , robert skinner, md d rebecca todd-bell e a division of dermatology, washington university school of medicine, st. louis, mo b washington university school of medicine, st. louis, mo c advanced dermatology and skin cancer associates, memphis, tn d division of dermatology, university of tennessee health science center, memphis, tn e central dermatology center, chapel hill, nc mycobacterium marinum, typically found in salt and fresh water environments, is a bacterium that can infect the skin after puncture and generally manifests as a localized granuloma or lymphangitis in a sporotricotic distribution. 1 m. marinum infection is typically seen in patients who have a history of exposure to aquariums. we report a unique case of m. marinum that developed on the right knee following participation in a hurricane katrina reconstruction project. a 47-year-old hispanic male presented with a three-year history of an asymptomatic hyperkeratotic pink plaque on the right knee that developed while doing carpentry work in post-katrina new orleans. the patient noted the lesion to be unresponsive to over-thecounter topical steroids and antifungal medications. he had no other medical history. other than the lesion, physical exam findings were negative (figure 1). a skin biopsy was performed on the lesion and sent for histologic examination with h&e staining, as well as fungal and mycobacterial abstract microbial exposure patterns are often altered as the result of natural disasters, causing certain infections with a normally characteristic epidemiologic profile to be seen in unfamiliar contexts. this phenomenon was well-demonstrated in new orleans following the devastation caused by hurricane katrina, with many relief workers experiencing unusual infections. we report a case of cutaneous mycobacterium marinum infection in a carpenter following participation in a hurricane katrina reconstruction project. introduction case report skin may 2018 volume 2 issue 3 copyright 2018 the national society for cutaneous medicine 203 tissue cultures. h&e staining demonstrated pseudoepitheliomatous hyperplasia with nodular chronic inflammation to the deep dermis with granulomatous perifolliculitis (figure 2). no fungal elements were observed on pas staining. fungal culture was negative at 4 weeks. mycobacterial culture demonstrated m. marinum at 4 weeks. figure 1. the patient presented with an ivory-white and pink hyperkeratotic plaque on the right knee. figure 2. there is pseudoepitheliomatous hyperplasia with chronic nodular inflammation to the deep dermis with granulomatous perifolliculitis. these findings are consistent with infection due to m. marinum. (h&e, 5x magnification). natural disasters create a unique exposure to rarely seen infectious agents. among hurricane katrina evacuees and rescue workers, there were at least 30 cases of methicillin-resistant staphylococcus aureus infection and 24 cases of hurricaneassociated vibrio vulnificus and v. parahaemolyticus wound infections reported. six of these infections resulted in death. 2 a 26-year-old relief worker with a three-month history of skin lesions, pulmonary symptoms, ataxia, and left-sided weakness was diagnosed with blastomycosis. 3 following a visit to her flooded new orleans home, an 85-year-old woman undergoing treatment with azathioprine for autoimmune hepatitis developed fever, chills, mild hypoxia, and dysuria, and she was subsequently diagnosed with urosepsis caused by buldvicia aquatica. this was the first reported case of b. aquatica infection in a patient. 4 when working up patients following natural disasters, clinicians should be mindful of alterations in the environment, just as they would a patient with a significant travel or occupational exposure history. following natural disasters, stagnant water, destroyed man-made and natural materials, and nonnative bacteria may be more prevalent in the environment and pose a significant risk to relief workers and returning evacuees. historically, cutaneous infection with m. marinum has been associated with people introduction skin may 2018 volume 2 issue 3 copyright 2018 the national society for cutaneous medicine 204 who handle fish and those who work in aquariums. 5 the course of infection is usually indolent but can occasionally follow a rapidly progressive course, resulting in sepsis. it is important to elicit a thorough history given the relative rarity of this condition. in the patient discussed above, exposure history was critical to broadening the differential diagnosis and workup to include cultures for less commonly encountered infectious agents along with routine bacterial and fungal stains and cultures. in addition to infections by m. marinum, infections by v. vulnificus and v. parahaemolyticus must also be considered in post-hurricane relief areas. 6 use of minocycline, clarithromycin, and ethambutol has been described for the treatment of m. marinum infection; our patient cleared infection with an extended half-year course of minocycline. in the case of deep or widespread infection, surgical intervention may be needed in addition to medical therapy. 4 conflict of interest disclosures: none funding: none corresponding author: zachary p. nahmias, md division of dermatology washington university school of medicine 660 south euclid avenue campus box 8123 st. louis, mo 63110 314-454-8622 (office) nahmias@wustl.edu references: 1. rallis e, koumantaki-mathioudaki e. treatment of mycobacterium marinum cutaneous infections. expert opin pharmacother. 2007;8(1744-7666 (electronic)):2965-2978. 2. jablecki j, norton sa, keller r, et al. infectious disease and dermatologic conditions in evacuees and rescue workers after hurricane katrina multiple states, august-september, 2005. j am med assoc. 2005;294(17):2158-2160. 3. szeder v, ortega-gutierrez s, frank m, jaradeh ss. cns blastomycosis in a young man working in fields after hurricane katrina. neurology. 2007;68(20):1746-1747. 4. corbin a, delatte c, besson s, et al. budvicia aquatica sepsis in an immunocompromised patient following exposure to the aftermath of hurricane katrina. j med microbiol. 2007;56(8):1124-1125. 5. nordén a, linell f. a new type of pathogenic mycobacterium [4]. nature. 1951;168(4280):826. 6. rhoads j. post-hurricane katrina challenge: vibrio vulnificus. j am acad nurse pract. 2006;18(7):318-324. doi:10.1111/j.17457599.2006.00139.x. skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 435 short communications eccrine nevus of the forearm controlled with topical glycopyrrolate ella n. glaser ms1, anastasia o. kurta do2, dee a. glaser md2 1university of missouri-kansas city school of medicine, kansas city, mo 2department of dermatology, saint louis university school of medicine, st. louis, mo eccrine nevus is a rare skin hamartoma with limited representation in literature. most commonly, it presents in childhood or early adolescence, but few cases have been reported presenting in late adulthood.1 the lesion is identified pathologically with a characteristic increased number and/or size of eccrine glands with a preserved morphology of the gland.2-3 the presentation of eccrine nevus can vary, with most presenting with localized hyperhidrosis without associated skin abnormalities, and others presenting with varied overlying skin changes in the absence of hyperhidrosis.4-5 these lesions occur equally in males and females and are most commonly found on the forearm.2 there are reports of successful treatment by surgical excision, topical aluminum chloride, systemic and topical anticholinergic agents, and botulinum toxin injection.2,4,6 a man in his 30s presented with a 21-year history of intermittent excessive perspiration localized to his left forearm. he had no significant past medical or surgical history. previously he tried using topical aluminum chloride products without improvement in his sweating and had a side effect of skin irritation and dryness. his focal hyperhidrosis lead to physical discomfort and embarrassment, especially since it interfered with the use of a computer keyboard at work. subjectively, he perceived his sweating as severe, with a grade of 4, on the hyperhidrosis disease severity scale (hdss). on physical examination, the patient had no visible cutaneous abnormalities. a minor starch iodine test was performed, which demonstrated a welldefined patch of hyperhidrosis on the patient’s left forearm (figure 1). based on the severity of his symptoms and negative effect on quality of life, several treatment options were offered, including botulinum toxin type a injections or compounded 1% glycopyrrolate cream, which he elected to try first. he applied the cream once daily for approximately 2 weeks to gain control of his symptoms. his sweating remains controlled after 2 years with once weekly maintenance application and without reported adverse effects as demonstrated by a post-treatment minor starch iodine test (figure 2). introduction case report skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 436 figure 1: left forearm after a minor starch iodine test highlighting localized hyperhidrosis. figure 2: minor starch iodine test after two-year long maintenance therapy with topical glycopyrrolate this figure shows significant improvement in hyperhidrosis severity. our patient presented with classic symptoms and location of an eccrine nevus and without other clinical exam findings. although a biopsy was offered, it is not required, and a starch iodine test is very helpful in making the diagnosis. management should be conservative. symptomatic focal hyperhidrosis of eccrine nevi can be successfully controlled with cost-effective, topical, anticholinergic therapy, as our patient demonstrates. we propose that it should be offered as first line treatment and can be used long term for maintenance therapy. topical antiperspirants are often ineffective at controlling symptoms and can also frequently cause irritation. topical anticholinergic therapy is well tolerated, easy to use, and minimizes the systemic side effects of oral anticholinergic use. conflict of interest disclosures: none. funding: none. corresponding author: ella glaser, ms university of missouri-kansas city school of medicine 2911 walnut street kansas city, mo email: engxtd@mail.umkc.edu references: 1. ruiz de erenchun f, vazquez-doval fj, mejuto fc, quintanilla e. localized unilateral hyperhidrosis: eccrine nevus. j am acad dermatol. 1992;27:115-6 2. jung wk, lee js, jung mj, whang kw, kim yk. a case of eccrine nevus. ann dermatol. 1995;7:270-2 3. kawaoka jc, gray j, schappell d, robinsonbostom l. eccrine nevus. j am acad dermatol. 2004;51:301-304 4. lera m, espana a, idoate ma. focal hyperhidrosis secondary to eccrine naevus successfully treated with botulinum toxin type a. clinical and experimental dermatol. 2015:640-43 5. kang mj, yu ds, kim jw. a case of eccrine nevus. annals of dermatol. 2008;20:29-31 6. dua j, grabcyznska s. eccrine nevus affecting the forearm of an 11-year-old girl successfully controlled with topical glycopyrrolate. pediatr dermatol. 2014;31:611-24 discussion mailto:engxtd@mail.umkc.edu skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 949 compelling comments generalized eruptive keratoacanthomas of grzybowski and the sign of zorro philip r. cohen, md1,2 1 department of dermatology, university of california, davis medical center, sacramento, ca 2 touro university california college of osteopathic medicine, vallejo, ca i read with interest the excellent case report by taylor et al.1 they described not only eruptive keratoacanthomas, but also welldifferentiated squamous cell carcinomas and prurigo nodules in a 59-year-old man with chronic kidney disease. they also shared the challenges encountered with the diagnosis and management of their patient’s skin lesions. generalized eruptive keratoacanthomas of grzybowski is a non-hereditary onset of hundreds to thousands of small keratoacanthomas that can appear not only on the skin but also the mucous membranes of the eyes and mouth. eyelid tumors may cause ectropion and lesions may occur on the buccal mucosa, lips, and tongue.1-5 masked facies, also referred to as hypomimia, is most associated with parkinson disease; however, this phenomenon has also been observed in other conditions (table 1).1-6 in addition, some patients with generalized eruptive keratoacanthomas of grzybowski present with masked facies. these can either present as sclerotic mask-like facies (or sclerodermalike masked facies) without any facial expression or they can appear as confluent individual keratoacanthomas that essentially cover the entire face like a mask.3-5 importantly, another distinctive--and possibly pathognomonic--salient feature of generalized eruptive keratoacanthomas of grzybowski is the sign of zorro.2 zorro--don diego de la vega--is a fictional spanish nobleman who defended the people by behaving as an outlaw against those who acted against them. he who wore a black mask that covered the areas around his eyes and the bridge of his nose to conceal his identity.2 the sign of zorro, in association with generalized eruptive keratoacanthomas of grzybowski, was initially described in 2014.2 it represents the prominent appearance of multiple individual and confluent keratoacanthomas predominantly restricted to the periorbital region--including the eyebrows, eyelids, and even extending to include the cutaneous and mucosal conjunctiva (figure 1a).2,5 since the distribution of keratoacanthomas presents like a mask covering these affected areas, this unique feature has more recently also been referred to as the mask of zorro.5 skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 950 table 1. clinical differential diagnosis of masked facies carbon monoxide poisoning fragile x-associated tremor/ataxia syndrome (fxtas) generalized eruptive keratoacanthomas of grzybowski (gekg) manganisma osmotic demyelination syndromeb pantothenate-kinase-associated neurodegeneration (pkan) parkinson disease progressive supranuclear palsy (psp) shy-drager syndrome athis is also referred to as manganese-associated neurotoxicity. bthis was associated with extrapontine myelinolysis and reversible parkinson disease after hyponatremia correction in a woman with a pituitary adenoma and hypopituitarism. figure 1. generalized eruptive keratoacanthomas of grzybowski-associated sign of zorro. a 68-year-old man, who had completed treatment for metastatic colon cancer six months earlier, presented with hundreds of pruritic small (1 to 5 millimeters) erythematous papules with a central umbilication and a horny, keratotic plug located on his head and neck, chest and abdomen, and arms and legs. he had a positive sign of zorro since the periorbital distribution of keratoacanthomas on his face--around his eyes and on the bridge of his nose--mimicked the mask of the fictional character zorro (a). acitretin was started; after the initial dose of 10 milligrams daily was increased to 40 milligrams daily, all the lesions eventually completely resolved. his mask of zorro was no longer present at a follow-up visit one month after stopping the acitretin treatment that he received for eight months (b). some of the details of this patient have previously been reported.2 skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 951 oral retinoids are often used in the initial management of generalized eruptive keratoacanthomas of grzybowski.1-5 therapy may not only require achieving the optimal dose to prevent new keratoacanthomas and progression of current tumors, but also several months of treatment to achieve complete resolution of all lesions and maintain clearance without new neoplasms developing.2,4 in conclusion, when a patient with generalized eruptive keratoacanthomas of grzybowski has a positive sign of zorro, successful intervention of the condition is characterized by disappearance of zorro’s mask (figure 1b).2 conflict of interest disclosures: none funding: none corresponding author: philip r. cohen, md 10991 twinleaf court san diego, ca 92131-3643 email: mitehead@gmail.com references: 1. taylor m, pham a, clausen m, darabi k. eruptive keratoacanthoma in a 59-year-old female with chronic kidney disease: a case report and review of treatment approaches. skin j cutan med. 2023;7(3):764-770. 2. anzalone cl, cohen pr. generalized eruptive keratoacanthomas of grzybowski. int j dermatol. 2014;53(2):131-136. 3. haas n, schadendorf d, henz bm, fuchs pg. nine-year follow-up of a case of grzybowski type multiple keratoacanthomas and failure to demonstrate human papillomavirus. br j dermatol. 2002;147(4):793-796. 4. relvas m, calvao j, coutinho i, cardoso jc. case for diagnosis. a pruritic eruption of keratotic papules over the face and neck. an bras dermatol. 2021;96(1):100-102. 5. parry f, sauniere d, huertas diaz dl, dandurand m. generalized eruptive keratoacathomas of grzybowski: a case report followed over 11 years. ann chir plast esthet. 2017;62(2):176-180. 6. hou x, zhang y, wang y, wang x, zhao j, zhu x, su j. a markerless 2d video, facial feature recognition-based, artificial intelligence model to assist with screening for parkinson disease: development and usability study. j med internet res. 2021;23(11):e29554. skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 343 compelling comments the cutaneous horn: fascinating since 1588 nicole nagrani bsa, adrianna gonzalez bsa, anna nichols md, phda,b adepartment of dermatology and cutaneous surgery, university of miami miller school of medicine, miami, fl bdepartment of dermatology and cutaneous surgery, sylvester comprehensive cancer center, miami, fl in 1588, margaret gryffith captured the attention of many after growing a four-inch horn from her forehead (figure 1a). according to folklore, margaret’s husband, just before his death, accused her of “giving him the horn,” a phrase implying that she had been unfaithful. margaret denied this allegation and countered that a horn would grow from her forehead if she had committed adultery. according to the legend, a horn did grow and suggested to people that this “unworldly horn” was a warning for others to repent their sins and ask god for forgiveness. margaret was put on display in london, attracting poets and playwrights, who would later document their observations in their writings.1 these descriptions are thought to be the first written record of a cutaneous horn. in 1598, 35-year-old frenchman francois trouvillou was discovered in france with a large, finger-length horn protruding from his forehead that curved backwards nearly penetrating his scalp.2 trouvillou’s case was documented in judge du thou’s historical anecdotes. in 1642 thomas bartholin encountered this report, which stimulated his interest in cutaneous horns and propelled figure 1. (a) a depiction of margaret gryffith (image reproduced with permission from the mary evans picture gallery). (b) table listing skin conditions associated with cutaneous horns. him to investigate them further. ultimately, bartholin concluded that cutaneous horns were not supernatural phenomenon as originally believed, but rather were produced by skin tumors. bartholin’s work prompted german scholar georg franck von franckenau to write the first article dedicated to the cutaneous horn. published in 1676, tractatus philologico-mediscus de cornutis describes a series of 25 cases of cutaneous horns reported by multiple medical dignitaries.2 skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 344 in 1791, everard home published an article supporting bartholin’s hypothesis that cutaneous horns were tumors that resulted from altered skin growth.3 it is now wellestablished that cutaneous horns are composed of cornified keratinaceous material, have a predilection for sunexposed skin, and can arise from benign, pre-malignant, and malignant skin lesions (figure 1b).2 conflict of interest disclosures: none. funding: none. corresponding author: nicole nagrani, bs department of dermatology and cutaneous surgery university of miami miller school of medicine nxn237@miami.edu references: 1. wood jo. woman with a horn. huntington library quarterly 1966; 29: 295–300. 2. bondeson j. everard home, john hunter, and cutaneous horns: a historical review. the american journal of dermatopathology. 2001;23(4):362369. 3. home e. observations on certain horny excrescences of the human body. philos trans r soc lond b biol sci 1791; 81: 95–105. mailto:nxn237@miami.edu skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 389 in-depth reviews a review of biologics and other treatment modalities in hiv-associated psoriasis joshua r. kaminetsky ba1,2, mina aziz ba1, shivani b. kaushik md1 1department of dermatology, icahn school of medicine at mount sinai, new york, ny 2albert einstein college of medicine, bronx, ny psoriasis is a common, chronic inflammatory condition caused by hyperproliferation and abnormal maturation of keratinocytes in the dermis. this results in erythematous plaques and papules with a silver scale, most commonly on the knees, elbows, scalp, and extensor surfaces of the limbs. while mild to moderate psoriasis can be managed with topical treatments and phototherapy, more pervasive and severe disease often necessitates the use of systemic agents. traditionally, acitretin, cyclosporine, and methotrexate were the only available systemic agents, but biologics are now becoming the first-line therapy for moderate to severe psoriasis. dermatologists are increasingly using biologics to treat psoriasis, owing to their high efficacy, but these potent medications are not administered without consideration of their risks. by nature of their immuneregulating molecular mechanisms, biologic agents often result in a relatively immunosuppressed state. their use can be particularly challenging in patients who are immunosuppressed at baseline, such as transplant recipients or hiv patients. according to the nih, about 2.2% of the united states population suffers from psoriasis, and this prevalence is similar if not abstract introduction psoriasis poses a significant challenge to dermatologists, and comorbid conditions may further exacerbate that challenge. this is especially true for conditions that compromise a patient’s immune status—such as human immunodeficiency virus (hiv)—as many of the most potent medications in the psoriasis armamentarium rely on immunomodulation. moreover, patients with hiv are often not included in clinical trials because of their immunocompromised state. therefore, most treatment recommendations rely on limited evidence derived from case reports and case series. this article reviews the current literature regarding management of hiv-associated psoriasis, with a particular focus on the relatively recent use of biologic agents in this population. though there is a risk of compounding patients’ suppressed immune status, the reports to date have demonstrated promise in treating hiv-associated psoriatic disease, and these agents may play a role in managing appropriately selected patients. skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 390 increased in hiv-positive patients. moreover, psoriasis in patients suffering from hiv can be more severe, often correlating with the degree of a patient’s immunosuppression.1 similarly, psoriatic arthritis is also noted to be more severe in this population.2 thus, these patients are often in need of the most efficacious systemic therapy to manage the severity of their psoriatic disease, yet their comorbid hiv-status relatively contraindicates one of the most potent classes of medication in the psoriasis armamentarium. data regarding the use of biologic agents in treating psoriasis in hiv patients is limited, as these patients are often not included in clinical trials. however, a continually growing number of case reports reveals an important role for these agents in treating hivassociated psoriasis without significant detriment to patients’ immune status. in this review, we discuss the challenges and considerations warranted in treating psoriasis in the hiv population, with a particular focus on biologics and the role they may play in treating psoriatic disease in hiv-positive patients. new onset psoriasis may be the presenting feature of hiv infection. in patients already suffering from psoriasis, hiv infection may exacerbate their course, resulting in more chronic, severe, and recalcitrant disease.3 thus, diligent management by a dermatologist is of the utmost importance in caring for these patients. given the crucial role of t-cells in psoriasis pathogenesis4 and the t-cell depletion that typically characterizes hiv infection, the correlative relationship between these two diseases seems somewhat paradoxical at first glance. however, it is suggested that cd8+ t-cells and the interferon-γ they produce are largely involved in psoriatic lesions5,6 while cd4+ t-lymphocytes are those destroyed in hiv. the relative imbalance between cd4 and cd8 cells that results from hiv-mediated cd4+ t-cell destruction is suggested to play a role in hiv-associated psoriasis, among other changes in the lymphocyte population and the relative amounts of various cytokines they produce.7 accordingly, by protecting cd4+ cells and mitigating the impact of this lymphocyte imbalance, antiretroviral therapy (art) may be an essential component of an hivassociated psoriasis treatment regimen. moreover, art may also have a secondary benefit by combating the effects of the proinflammatory cytokine tnf-α2, believed to contribute to both hiv and psoriasis pathogenesis. mechanistic hypotheses aside, while the nature of the biomolecular relationship between hiv and psoriasis continues to be explored, the clinical evidence is strongly suggestive of art’s utility in managing hiv-associated psoriasis. there are a notable number of reports supporting the use of art in combating hiv-associated psoriasis5,8,9,10,11, even administered as monotherapy.12 it should be noted that while art has demonstrated success in treating hivassociated psoriasis, the degree to which it responds varies from patient to patient. nonetheless, patients whose psoriatic disease does not respond to antiretrovirals should strongly consider continuing on an optimal art regimen under the care of a qualified infectious disease specialist. these medications are a cornerstone of hiv hiv associated psoriasis & antiretroviral therapy skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 391 management, and suppressing viral replication will help protect against the other pernicious ramifications of cd4+ t-cell depletion13, including other hiv-related dermatologic conditions. in addition to managing a patient’s immune status, first-line treatment for mild hivassociated psoriasis relies on targeted modalities such as topical agents, as is recommended in the general population. commonly used medications include topical corticosteroids, calcipotriol14, tazarotene, and a variety of formulations combining two of the abovementioned medications.2 by nature of their limited and localized effects, topical medications pose little risk of compounding the immunosuppressive state in hiv. overall, they can be safely used in this population and the adverse effect profile is the same as would be expected in the general population. limitations of topical therapy include lack of potency, limited field coverage, and inconvenience of application, especially if disease is more widespread. accordingly, first-line treatment for moderate to severe psoriatic disease in patients who are averse to topical agents includes ultraviolet phototherapy, which inhibits cell proliferation and inflammation.2,7 reports of cases treated with psoralen and ultraviolet a (puva) or ultraviolet b (uvb) have demonstrated clinical improvement of hivassociated psoriasis.15,16,17,18 although some animal and in vitro studies have noted possible activation of hiv by uv radiation19, most reports suggest safe use in clinical practice without detriment to cd4+ t-cell counts or increases in viral load.18,20 traditional systemic agents serve as possible options for patients intolerant of and/or unresponsive to art, topical agents, and phototherapy. traditional systemic agents include acitretin, methotrexate and cyclosporine. among these agents, acitretin has the notable advantage of not causing or exacerbating immunosuppression. in a 20 week study of 11 hiv-positive patients with moderate to severe psoriasis treated with 100mg of acitretin, 4 patients achieved greater than 75% reduction in their psoriasis area and severity index (pasi) score, with another 2 achieving 51-75% reduction.21 side effect profile of retinoids, including dryness, hypertriglyceridemia and hepatotoxicity remains the same in hiv population, but clinicians should be especially vigilant in monitoring for pancreatitis, as its risk can be increased in combination with certain art medications.2 methotrexate has been used successfully to treat psoriasis for over half a century, but its immunosuppressive and hepatotoxic effects are of particular concern in the hiv population. a handful of case reports have documented effective treatment with methotrexate22,23, but weighing the risks of immunosuppression against the therapeutic benefits is critical, as it has been notably associated with an increased risk of opportunistic infections.23 therefore, methotrexate is traditionally reserved for the most severe cases of hiv-associated psoriasis and should be used cautiously with close collaboration of a dermatologist and infectious disease specialist.7,23 phototherapy traditional systemic agents topical therapy skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 392 similarly, there are a handful of case reports of successful cyclosporine use in hiv patients with psoriasis. while cyclosporine is also immunosuppressive, there has been no notable increase in opportunistic infections with its use.24,25 in fact, it is hypothesized that cyclosporine’s ability to prevent t-cell activation may slow the destruction of immune cells by hiv.25 nonetheless, cyclosporine should be administered judiciously in this population. if given, trough serum levels should be monitored, especially in patients whose hiv regimens contain protease inhibitors or other medications used for opportunistic infection prophylaxis, as these agents can increase bioavailability of cyclosporine.26 the past decade has seen a paradigm shift in psoriasis pathogenesis leading to development of highly efficacious and safe biologic agents. in the two decades since etanercept was first approved for treatment of rheumatoid arthritis, biologic agents have continually demonstrated efficacy in treating a wide variety of ailments across the vast spectrum of medical specialties. however, their use in the hiv population is a more nuanced matter. data regarding biologic use in hiv patients is scarce owing to their relative recency and lack of clinical trials, making blanket recommendation algorithms difficult to generate. theoretically, anti-tnf-α biologic agents could have several desirable roles in hivassociated psoriasis. in addition to contributing to the inflammation underlying psoriasis, tnf-α may also contribute to hiv disease progression. though its exact role in hiv pathogenesis is not certain, tnf-α is overexpressed at all stages of hiv infection, and it is hypothesized to enhance hiv expression and replication through nf-κβ signaling and assist in cd4+ lymphocyte programmed cell death.27 it may also underlie the manifestations of fever, fatigue, and cachexia in the setting of advanced hiv/acquired immunodeficiency syndrome (aids).7 tnf-α blockade can thus serve several purposes in patients with hivassociated psoriasis. on the other hand, tnf-α is also an essential inflammatory mediator of the immune system, and its suppression should be handled cautiously in the setting of systemic immunodysfunction secondary to hiv infection.27 in the general population the iatrogenic tnf-α suppression resulting from these biologic agents leaves patients more susceptible to infectious insult, and it is not clear to what extent this phenomenon is potentiated in hiv-positive patients. despite these concerns, a growing number of case reports have demonstrated success with anti-tnf-α and other biologic agents in treating hiv-associated psoriasis. moreover, the vast majority of cases demonstrate no detriment to cd4 lymphocyte counts, serum viral loads, overall immune status, and susceptibility to infection. in fact, cd4 count increased in a majority of patients following treatment. tables 1-3 summarize the reports to date utilizing common anti-tnf-α therapies in treating refractory hivassociated psoriasis. adalimumab is a human monoclonal antibody that binds and prevents the activity of solubilized and bound tnf-α (table 1). a couple of case reports in just the last few years have demonstrated safe and successful use of this drug in treating psoriasis refractory to other modalities. lindsey et al notes complete clearance of a biologics skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 393 patient’s psoriasis after failing numerous treatments.1 the patient was treated for 30 months and experienced no adverse effects. etanercept is a soluble receptor fusion protein that binds solubilized tnf-α and prevents its interaction with cell surface receptors (table 2); it has been used most frequently among the biologic agents in the hiv-associated psoriasis literature. mikhail et al reported that not only did the psoriasis resolve in one patient, but his presenting leukocytosis and fevers normalized as well.28 linardaki et al and di lernia et al met similar success, notably without aggravating their respective patients’ hepatitis c coinfection.29,30 bardazzi et al discusses the largest case series hitherto in the literature on biologic treatment of hiv-associated psoriasis, in addition to the longest followup.31 he concludes that more evidence is necessary, but preliminary data support the use of these medications with appropriate monitoring. it is worth mentioning the report of fatal infection in the etanercept report by aboulafia et al that ultimately resulted in the patient’s death.32 infliximab, is a chimeric monoclonal antibody that has higher affinity for tnf-α and hence a higher potency (table 3).33 indeed, cepeda et al demonstrated successful use of infliximab for treatment of psoriasis in hiv patients who insufficiently responded to etanercept.34 sellam et al similarly reported a few cases whose skin and debilitating psoriatic arthritis responded favorably upon addition of infliximab to their methotrexate regimen.35 as evidenced by these cases, the vast majority of patients responded well to biologics intervention, with no deleterious effect on cd4 count, viral load, or immune status. in addition to the anti-tnf-α agents, other biologics also seem promising in hivassociated psoriasis. several reports cite successful use of ustekinumab, which was well-tolerated by patients (table 4). ustekinumab targets other inflammatory immune-regulating cytokines, notably il-12 and il-23. having agents with alternative molecular mechanisms and targets can be beneficial, as wieder et al demonstrated treatment success using ustekinumab after failing several anti-tnf-α agents.37 saeki et al also administered ustekinumab after the patient did not respond to numerous medications, including adalimumab.38 similar to tnf-α inhibitors, however, ustekinumab should be reserved for severe cases, as il-12 and il-23 play a role in warding off opportunistic infections in the hiv population.39 overall, while the success of biologics has been encouraging, due to the theoretical immunosuppressive risks, current recommendations favor their use only for cases that are unresponsive to other therapies.2 anti-tnf-α therapy may promote opportunistic infections and increase the risk of lymphoproliferative malignancies that result from hiv-induced immunedysregulation, as well as possibly reactivating latent tuberculosis, a potential complication present even in the general immunocompetent population while on biologic agents.42 further research is necessary, and concomitant antiretroviral regimens are recommended to reduce the risk of developing complications during treatment with these potent agents.2,7,35 skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 394 table 1. adalimumab report cohort treatment results lindsey et al.1, 2014 • 49 y.o. male with pso, psa, hiv on art • minimally responsive to acitretin, phototherapy, and topical agents • cd4: 127 • vl: 14,649 • loading dose of 80mg, followed by 40mg every other week • 30 months course • therapy yielded complete clearance of skin disease and near complete resolution of joints • last viral load undetectable • transient decrease in cd4 count managed with change in art regimen bardazzi et al.31, 2017 • 2 patients with hiv and moderate-tosevere pso • both failed csa therapy • patient 1 cd4: 472, not on art • patient 2 cd4: 725, on art • loading dose of 80mg, 40mg at week 1, then 40mg every 2 weeks thereafter • both patients reached 75% reduction in pasi • no adverse effects, including infections • transient, clinically insignificant reduction in cd4 • patient 1 cd4: 456 • patient 2 cd4: 800 table 2. etanercept report cohort treatment results aboulafia et al.32, 2000 • 45 y.o. male with hiv on art, pso and debilitating psa • failed corticosteroids, hydroxychloroquine, minocycline • cd4: 20; vl: 14,000 • 25 mg twice weekly for 8 weeks • dramatic improvement of skin and joint disease • cd4 and viral counts remained stable • however, recurrent microbial infections requiring abx led to cessation of therapy linardaki et al.29, 2007 • 42 y.o. male with hiv on art, hcv, pso, psa and hemophilia a • failed mtx and csa • cd4: 380; vl: 4,100 • 25 mg twice weekly for 2 years (ongoing) • complete remission of pso within 1 month • no change in liver panel • cd4 > 450; vl: undetectable mikhail et al.28, 2008 • 32 y.o. male with von zumbusch pustular pso, psa, and hiv on art • failed topical • 50 mg weekly (ongoing) • complete remission of skin within 4 weeks, though mild recurrence noted • cd4: 633; vl: undetectable • no infectious episodes skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 395 treatment • cd4: 435; vl: < 75 di lernia et al.30, 2013 • 51 y.o. male with widespread pso, hiv on art, hcv, and alcoholism • failed corticosteroids, acitretin, csa, phototherapy • pasi: 13.4 • cd4: 200-499; vl: 7,930 • 50 mg twice weekly for 12 weeks, then 50 mg weekly • 132 weeks • pasi reduced to 6.2 • cd4 remained stable; vl: undetectable • no significant infectious episodes • mild relapses of pso managed with topical therapy de simone et al.6, 2016 • 50 y.o. male with pso, hiv on art, and hcv • failed acitretin and topicals • previous hbv infection • pasi: 24.2 • cd4: 445 • 50 mg twice weekly for 12 weeks, then 50 mg weekly • 6 months (ongoing) • pasi reduced to 1.8 • no significant change in viral load, cd4 count, hcv viral load, and liver tests • no hbv reactivation • mild relapses of pso managed with topical therapy bardazzi et al.31, 2017 • 4 patients with hiv and moderate-tosevere pso • all failed csa therapy • patient 1 cd4: 486, not on art • patient 2 cd4: 1000, on art • patient 3 cd4: 265, on art • patient 4 cd4: 870, on art • 50 mg twice weekly for 12 weeks, then 50 mg weekly • all patients reached 75% reduction in pasi • no adverse effects, including infections • transient reduction in cd4 • patient 1 cd4: 491 • patient 2 cd4: 1000 • patient 3 cd4: 350 • patient 4 cd4: 885 table 3. infliximab report cohort treatment results bartke et al.36, 2004 • 46 y.o. male with pso, psa, and hiv on art • failure of acitretin, mtx, corticosteroids, phototherapy and • infliximab 3 mg/kg loading does, at 2 weeks and 6 weeks • rapid response of skin and joints within 2 days • serum hiv rna remained undetectable during treatment • cd4: 107 skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 396 topicals • cd4: 193 sellam et al.35, 2007 • patient 1 had hiv on art, pso, psa, debilitating arthritis, sacroilitis, 2º syphilis, and urethritis; pso failed topicals, prednisone, and mtx • patient 1 cd4: 425; vl: <50 • patient 2 had hiv on art, pso, and psa; pso failed topicals, acitretin • patient 2 cd4: 16; vl: 300,000 • patient 1: 20mg at weeks 0, 2, 6 and then every 8 weeks • total of 15 infusions • received infliximab in addition to continued mtx • patient 2: 2 mg/kg at weeks 0, 2, 6 and then every 8 weeks • total of 25 infusions • received infliximab in addition to continued mtx • both patients had dramatic improvement of skin and joint disease • cd4 and vl largely unchanged • no adverse effects nor infectious episodes • patient 1 experienced escape phenomenon, managed with increase in dosing frequency cepeda et al.34, 2008 • review of 8 hiv patients with rheumatic disease refractory to other treatment • of 8, 3 had psa and pso • patient 1 cd4: 750; vl: 22,148, not on art • patient 2 cd4: 268, vl: <50, on art • patient 3 cd4: 446, vl: < 400, on art • all psoriatic patients received some combination of biologic agents, adding to the regimen if the previous agent was insufficient (etanercept 25 mg twice weekly, adalimumab 40 mg every other week, infliximab 5 mg/kg every 6-8 weeks) • while some had moderate responses to adalimumab and etanercept, response to infliximab was satisfactory across all patients • treatment durations from 13-55 months • all 3 pso patients has nearcomplete clearing of skin • patient 1 cd4: 741; vl: 54,227 • patient 1 had transient increase in viral load responsive to temporary discontinuation and subsequent resumption of medication • patient 2 cd4: 417; vl: <50 • patient 2 had facial abscess responsive to abx • patient 3 cd4: 456; vl: <400 skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 397 table 4. ustekinumab report cohort treatment results paparizos et al.40, 2011 • 61 y.o. male with hiv and pso • unresponsive to art, acitretin, phototherapy, mtx, csa and etanercept • pasi: 11.9 • cd4: 429; vl: < 50 • 45 mg at weeks 0, 4, and 16 • maintenance dose of 45 mg every 12 weeks (ongoing) • pasi reduced to 2.7 at week 12 • achieved 90% reduction by week 18 • increase in cd4 • no adverse effects wieder et al.37, 2014 • 39 y.o. male with hiv on art, pso, and psa • failed topicals, phototherapy, mtx, acitretin, hydroxyurea, etanercept, adalimumab, golimumab • pasi: 48 • cd4: 847; vl: undetectable • total of six 45mg doses and one 90-mg dose • erratic dosing schedule due to poor patient compliance • pasi reduced to 19 • cd4 remained stable and viral load remained undetectable • only notable side effect were genital condylomata acuminate, also present before treatment saeki et al.38, 2015 • 47 y.o. male with hiv on art and plaque pso • failed uvb, csa, etretinate, adalimumab • pasi: 15.1; it decreased to 1.7 with adalimumab, but then increased to 9.7 • cd4: 602; vl: 29 • 45 mg every 3 months • 4 months (ongoing) • sustained pasi reduction to 0.8 • no adverse effects or change in cd4; vl < 20 bardazzi et al.31, 2017 • 4 patients with hiv and moderate-tosevere pso • all failed csa therapy • patient 1 cd4: 523, on art • patient 2 cd4: 537, on art • patient 3 cd4: 186, on art • 45 mg at week 0 and week 4, and every 12 weeks thereafter • all patients reached 75% reduction in pasi • transient reduction in cd4 • relapses were noted in 2 patients, managed by addition of phototherapy • patient 1 cd4: 454 • patient 2 cd4: 606 • patient 3 cd4: 330 • patient 4 cd4: 610 skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 398 • patient 4 cd4: 535, on art carpentieri et al.41, 2017 • 4 patients with hiv on art and pasi values ranging from 16.2 to 19 • failed traditional systemic therapies • not specified • all experienced 75% reduction in pasi score • well-tolerated • cd4 count increased in 3 patients abbreviations: abx = antibiotics, art = antiretroviral therapy, cd4 = cd4+ t-cell count in cells/mm3, csa = cyclosporine, hbv = hepatitis b virus, hcv = hepatitis c virus, mtx = methotrexate, pasi = psoriasis area severity index, pso = psoriasis, psa = psoriatic arthritis, vl = viral load in copies/ml, wbc = white blood cell count, y.o. = years old skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 399 unfortunately, there are no randomized controlled trials assessing the efficacy and safety of commonly used psoriasis treatments in the hiv population. most data are derived from anecdotal evidence such as case reports and case series.2 with that said, these isolated reports, particularly those on biologics, are slowly coalescing into a more robust literature that can help guide clinicians in determining the most appropriate treatment for psoriasis in hivpositive patients. psoriasis in its own right, particularly if severe, poses numerous challenges to dermatologists, and these are only compounded in the hiv population. psoriasis in hiv patients should be treated as per guidelines of national psoriasis foundation and require the coordinated interdisciplinary care of dermatologists and infectious disease specialists.2 additional studies are necessary to further explore the utility of these potent agents in treating hiv-associated psoriasis, but the reported cases thus far have been promising. conflict of interest disclosures: none. funding: none. corresponding author: joshua kaminetsky 1425 madison avenue, 15th floor new york, ny 10029 email: jkaminet@mail.einstein.yu.edu references: 1) lindsey sf, weiss j, lee es, et al. treatment of severe psoriasis and psoriatic arthritis with adalimumab in an hiv-positive patient.
 j drugs dermatol. 2014;13:869-871. 2) menon k, van voorhees as, bebo bf jr, et al. psoriasis in patients with hiv infection: from the medical board of the national psoriasis foundation. j am acad dermatol. 2010;62:291. 3) mallon e, bunker cb. hiv-associated psoriasis. aids patient care & stds. 2000;14:239-46 
 4) monteleone g, pallone f, macdonald tt, et al. psoriasis: from pathogenesis to novel therapeutic approaches. clin sci (lond). 2010;120(1):1-11. 5) fischer t, schwörer h, vente c, et al. clinical improvement of hivassociated psoriasis parallels a reduction of hiv viral load induced by effective antiretroviral therapy. aids. 1999;13:628. 6) de simone c, perino f, caldarola g, et al. treatment of psoriasis with etanercept in immunocompromised patients: two case reports. j int med res. 2016;44:67-71. 7) morar n, willis-owen sa, maurer t, et al. hiv-associated psoriasis: pathogenesis, clinical features, and management. lancet infect dis. 2010;10:470-78. 8) kaplan mh, sadick ns, wieder j, et al. antipsoriatic effects of zidovudine in human immunodeficiency virusassociated psoriasis. j am acad dermatol. 1989; 20:76. 9) duvic m, crane mm, conant m, et al. zidovudine improves psoriasis in human immunodeficiency virus conclusion mailto:jkaminet@mail.einstein.yu.edu skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 400 positive males. arch dermatol. 1994;130:447. 10) mahajan vk, sharma nl, sarin s, et al. triple antiretroviral therapy improves psoriasis associated with human immunodeficiency virus infection: a clinico-therapeutic experience. j eur acad dermatol venereol. 2008;22:1017. 11) mamkin i, mamkin a, ramanan sv. hiv-associated psoriasis. the lancet infectious diseases. 2007;7:496. 12) vittorio luigi de socio g, simonetti s, stagni g. clinical improvement of psoriasis in an aids patient effectively treated with combination antiretroviral therapy. scand j infect dis. 2006; 38:74. 13) günthard hf, saag ms, benson ca, et al. antiretroviral drugs for treatment and prevention of hiv infection in adults: 2016 recommendations of the international antiviral society-usa panel. jama. 2016;316:191. 14) gray jd, bottomley w, layton am, cotterill ja, monteiro e. the use of calcipotriol in hiv-related psoriasis. clin exp dermatol. 1992;17:342-3. 15) breuer-mcham j, marshall g, adu-oppong a, et al. alterations in hiv expression in aids patients with psoriasis or pruritus treated with phototherapy. j am acad dermatol. 1999; 40:48. 16) meola t, soter na, ostreicher r, et al. the safety of uvb phototherapy in patients with hiv infection. j am acad dermatol. 1993; 29:216.
 17) ranki a, puska p, mattinen s, et al. effect of puva on immunologic and virologic findings in hiv-infected patients. j am acad dermatol. 1991;24:404-10. 18) pechère m, yerly s, lemonnier e, et al. impact of puva therapy on hiv viremia: a pilot study. dermatology. 1997; 195:84. 19) cavard c, zider a, vernet m, et al. in vivo activation by ultraviolet rays of the human immunodeficiency virus type 1 long terminal repeat. j clin invest. 1990; 86:1369. 20) fotiades j, lim hw, jiang sb, et al. efficacy of ultraviolet b phototherapy for psoriasis in patients infected with human immunodeficiency virus. photodermatol photoimmunol photomed. 1995;11:107-11. 
 21) buccheri l, katchen br, karter aj, cohen sr. acitretin therapy is effective for psoriasis associated with human immunodeficiency virus infection. arch dermatol. 1997;133:711. 22) masson c, chennebault jm, leclech c. is hiv infection contraindication to the use of methotrexate in psoriatic arthritis? j rheumatol. 1995;22:2191. 23) maurer ta, zackheim hs, tuffanelli l, et al. the use of methotrexate for treatment of psoriasis in patients with hiv infection. j am acad dermatol. 1994;31:372-5. 24) allen br. use of cyclosporin for psoriasis in hiv-positive patient. lancet. 1992;339:686. 25) tourne l, durez p, van vooren jp, et al. alleviation of hiv-associated psoriasis and psoriatic arthritis with cyclosporine. j am acad dermatol. 1997;37:501. 26) rosmarin dm, lebwohl m, elewski be, et al. cyclosporine and psoriasis: 2008 national psoriasis foundation consensus conference. j am acad dermatol. 2010; 62:838. 27) calabrese lh, zein n, vassilopoulos d. safety of antitumor necrosis factor (anti-tnf) therapy in patients with chronic viral infections: hepatitis c, skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 401 hepatitis b and hiv infection. ann rheum dis. 2006;65:983-9 28) mikhail m, weinberg jm, smith bl. 2008. successful treatment with etanercept of von zumbusch pustular psoriasis in a patient with human immunodeficiency virus. arch. dermatol. 144:453– 456. 29) linardaki g, katsarou o, ioannidou p. effective etanercept treatment for psoriatic arthritis complicating concomitant human immunodefiency virus and hepatitis c virus infection. j rheumatol. 2007;34(6):1353-5. 30) di lernia f, zoboli g, ficarelli e. longterm management of hiv/hepatitis c virus associated with etanercept. indian j dermatol venereol leprol. 2013;79(3):444. 31) bardazzi f, magnano m, campanati a, et al. biologic therapies in hivinfected patients with psoriasis: an italian experience. acta derm venereol. 2017;97(8):989-990. 32) aboulafia dm, bundow d, wilske k, et al. etanercept for the treatment of human immunodeficiency virusassociated psoriatic arthritis. mayo clin proc. 2000; 75:1093. 33) scallon b, cai a, solowski n, et al. binding and functional comparisons of two types of tumor necrosis factor antagonists. j pharmacol exp ther. 2002; 301:418-26. 34) cepeda ej, williams fm, ishimori ml, et al. the use of anti-tumour necrosis factor therapy in hiv-positive individuals with rheumatic disease. ann rheum dis. 2008; 67:710. 35) sellam j, bouvard b, masson c, et al. use of infliximab to treat psoriatic arthritis in hiv-positive patients. joint bone spine. 2007; 74:197. 36) bartke u, venten i, kreuter a, et al. human immunodeficiency virusassociated psoriasis and psoriatic arthritis treated with infliximab. br j dermatol. 2004; 150:784. 37) wieder s, routt e, levitt j, et al. treatment of refractory psoriasis with ustekinumab in an hiv-positive patient: a case presentation and review of the biologic literature. journal of psoriasis and psoriatic arthritis. 2014;20(3):96-102. 38) saeki h, ito t, hayashi m, et al. successful treatment of ustekinumab in a severe psoriasis patient with human immunodeciency virus infection. j eur acad dermatol venereol. 2015;29:1653-1655. 39) yannam gr, gutti t, poluektova ly. il23 in infections, inflammation, autoimmunity and cancer: possible role in hiv-1 and aids. j neuroimmune pharmacol. 2012;7:95-112. 40) paparizos v, rallis e, kirsten l, kyriakis k. ustekinumab for the treatment of hiv psoriasis. j dermatolog treat. 2012;23:398. 41) carpentieri a, silvestris r, mascia p, et al. evaluation of efficacy and safety of biological therapy in patients with psoriasis and hiv coinfection. j am acad dermatol. 2017;76(6):ab128. 42) patel rv, weinberg jm. psoriasis in the patient with human immunodeficiency virus, part 2: review of treatment. cutis. 2008;82(3):202-10. skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 174 brief article a sweet presentation of a bitter disease: acute febrile neutrophilic dermatosis associated with coccidioidomycoses zainab a. jafri, do1, lydia shedlofsky, do2, andrew newman, do2, travis lam, do2, yebabe mengesha, md2 1arizona college of osteopathic medicine, glendale, az 2affiliated dermatology and dermatology department at honor health, scottsdale, az acute febrile neutrophilic dermatosis (afnd) was first described by robert douglas sweet in 1964 and thus eponymously termed sweet syndrome.1,2 afnd is subdivided into three categories based on clinical settings: classic, malignancy-associated, and drug-induced.3,4 classic afnd is described in association with infections, inflammatory bowel disease, and pregnancy. most commonly, classic afnd follows upper respiratory infection but has also been associated with yersinia, tuberculosis, histoplasmosis, and toxoplasmosis. coccidioidomycosisassociated afnd has rarely been reported in literature. afnd is an uncommon inflammatory condition characterized clinically by sudden onset of erythematous skin eruption, presenting as papules, nodules, and plaques commonly on the upper extremity, trunk, neck, and face.1 the histological hallmark is variably dense dermal infiltrate largely composed of mature neutrophils, together with edema of the papillary dermis.5 coccidioidomycosis, also known as valley fever, is an airborne, fungal disease caused by coccidioides immitis or coccidioides posadasii, a soil-dwelling fungus prevalent in regions of southwestern north and central america.7 during 1998-2014, there were ∼147,000 coccidioidomycosis cases reported to the centers for disease control and prevention (cdc) with, approximately two thirds occurring among arizona residents.8 this typically presents as a subclinical pulmonary infection, with selfresolution in immunocompetent individuals. the skin along with lymph nodes, meninges, and the musculoskeletal system, are the abstract acute febrile neutrophilic dermatosis, also known as sweet syndrome, is an uncommon inflammatory disorder. though the exact etiology is unclear, it has been presented in association with various entities. the majority of cases present following upper respiratory infections or viral gastroenteritis. other causes include drug-induced reactions, pregnancy-related manifestations, or in association with specific hematologic or solid tumors. rarely, it has been associated with coccidioidomycosis, a prevalent fungus endemic to the southwestern regions of the united states with a literature review revealing only three previous cases of coccidioidomycosis-associated sweet syndrome. here we report two new cases in individuals residing in arizona. introduction skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 175 most common sites of disseminated infection. cutaneous involvement generally presents as polymorphous lesions, resembling acne or rosacea. herein we examine two cases of afnd secondary to coccidioidomycosis. case report one a 55-year-old woman presented to her primary care physician with shortness of breath and rash. she was empirically treated with cefuroxime and amoxicillin without resolution in symptoms. subsequently she presented to outpatient dermatology clinic a month later for evaluation of the rash. she presented with deep red, sharply demarcated nodules and papules that appeared edematous and vesiculated, some coalescing into larger groups, bilaterally on upper and lower extremities, back, chest and abdomen (figure 1). no lesions appeared on the palms or soles. two 4 mm punch biopsies were obtained from the thighs, and lab work was drawn. the biopsies returned with interstitial granulomatous dermatitis with papillary dermal edema and eosinophils, negative for fungal organisms, consistent with histiocytoid sweet syndrome. further workup resulted yielded positive serology for coccidioidomycosis igm and igg antibodies. she was referred to the infectious disease team, who initiated treatment with oral fluconazole and oral corticosteroids. she continued to follow up, gradually tapering the oral steroids. at four months the rash had resolved leaving only post-inflammatory hyperpigmentation. case report two a 57-year-old homeless gentleman presented to the emergency department figure 1. left medial lower extremity revealing classic afnd architecture of erythematous plaques complaining of a cough and a diffuse rash. he was initiated on ceftriaxone and azithromycin after being diagnosed with left lower lobe pneumonia. review of systems was positive for headaches, fever, shaking chills, and nausea. the dermatology service was consulted due to diffuse large, erythematous nodules coalescing into plaques on the left shoulder and neck (figure 2). on physical examination firm nodules on the right forearm and chest were noted with several scattered vesicles on the extremities. vesicles were swabbed for bacterial and viral cultures, with negative findings and several skin biopsies were obtained. serology confirmed the presence of coccidioidomycosis with a positive igm. biopsies revealed diffuse neutrophilic infiltrate with perivascular nuclear dust and massive papillary edema, all consistent with afnd. infectious disease and pulmonology services were consulted, and the patient was initiated on intravenous corticosteroids with discussion of need for anti-fungal medications and careful monitoring. he case presentation https://assets.cureus.com/uploads/figure/file/108548/lightbox_56a6e6d0986c11ea8a1ebf6fdd47556e-1---new.png skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 176 gradually improved throughout his hospital stay but was lost to follow up upon discharge. figure 2. posterior neck. indurated erythematous nodules and pseudovesicles the diagnosis of classic afnd requires the presence of both major criteria and two out of the four minor criteria (table 1).4 symptoms and clinical manifestations typically respond rapidly to high-dose systemic corticosteroids. second-line systemic agents include colchicine, dapsone, tnf-alpha antagonists and cyclosporine.4,6 the pathogenesis for acute febrile neutrophilic dermatosis (afnd) is not fully elucidated but may be related to cytokinemediated recruitment of neutrophils to the skin. for this reason, afnd is treated firstline with corticosteroids, especially with extensive involvement, and has historically shown dramatic resolution. this disease has been associated with several clinical settings, and treatment should be guided by the underlying cause. though rare, in endemic areas underlying fungal etiologies must be considered and diagnostic tests should be considered when index of suspicion is high, such as these two cases. confirmatory testing for coccidioidomycosis is needed for diagnosis. diagnostic modalities such as serology, culture, and antibody screen are useful, as symptoms may be nonspecific. table 1. sweet syndrome diagnostic criteria criteria major criteria 1. abrupt onset of painful erythematous plaques or nodules 2. histopathological evidence of dense neutrophil infiltrate in the dermis without evidence of leukocytoclastic vasculitis minor criteria 1. fever > 38 °c 2. association with an underlying hematological, or visceral malignancy, inflammatory disease, or pregnancy, or preceded by an upper respiratory or gastrointestinal infection or vaccination 3. response to treatment with potassium iodide or steroids 4. abnormal laboratory values (3 of the following 4) a. erythrocyte sedimentation rate greater than 20 mm/h b. positive c-reactive protein c. >8,000 leukocytes d. >70% neutrophils diagnosing the appropriate cause of afnd is critical in the treatment and management of the disease. general first-line therapy, corticosteroids, should be avoided as the sole treatment modality in infectious etiologies.9 patients with afnd secondary to coccidioidomycosis will typically require antifungal medication. azole antifungals, specifically fluconazole and itraconazole are the initial therapy of choice for disseminated infections.7 therefore, close monitoring and referral to infectious disease is recommended. in this setting consideration for optimization of therapy and management discussion https://assets.cureus.com/uploads/figure/file/108551/lightbox_e5358000986c11ea9c4013f253ea7764-3---new.png skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 177 of the overall infection will improve prognosis and reduce patient morbidity. these unique cases of coccidioidomycosisassociated sweet syndrome demonstrate the importance of consideration of this uncommon etiology. importance should be given to individuals residing in the endemic regions, such as southwestern regions of the united states or with recent travel to these areas. in conclusion, until now, three cases of coccidioidomycosis-associated acute febrile neutrophilic dermatosis (afnd) have been reported.10 coccidioides, fungi endemic to the southwestern regions of the united states, central, and south america is a common pathogen that must be considered in patients presenting with clinical signs of afnd. these patients should be followed with a treatment plan of antifungal therapy, in addition to systemic corticosteroids, to appropriately treat these rare cutaneous manifestations. conflict of interest disclosures: none funding: none corresponding author: lydia b. shedlofsky, do affiliated dermatology honor health 20401 n 73rd street #230 scottsdale, az 85255 phone: 480-556-0446 fax: 480-556-0447 email: lshedlofsky@affderm.com references: 1. korkut m. a dermatologic emergency; sweet’s syndrome. the american journal of emergency medicine. 2019;37(9):1807.e1-1807.e3. doi:10.1016/j.ajem.2019.06.012 2. sweet’s syndrome (acute febrile neutrophilic dermatosis) journal of the american academy of dermatology. accessed june 19, 2020. https://www.jaad.org/article/s01909622(94)70215-2/pdf 3. nelson ca, noe mh, mcmahon cm, et al. sweet syndrome in patients with and without malignancy: a retrospective analysis of 83 patients from a tertiary academic referral center. journal of the american academy of dermatology. 2018;78(2):303-309.e4. doi:10.1016/j.jaad.2017.09.013 4. cohen pr, kurzrock r. sweet’s syndrome. am j clin dermatol. 2002;3(2):117-131. doi:10.2165/00128071-200203020-00005 5. secchin p, gomes mk, quintella dc, et al. idiopathic histiocytoid sweet syndrome: a case report with clinical and histopathological considerations. int j dermatol. 2018;57(10):1182-1186. doi:10.1111/ijd.14159 6. heath ms, ortega-loayza ag. insights into the pathogenesis of sweet’s syndrome. front immunol. 2019;10:414. doi:10.3389/fimmu.2019.00414 7. “the acutely ill patient with fever and rash.” mandell, douglas, and bennett's principles and practice of infectious diseases, by john e. bennett et al., 9th ed., elsevier / saunders, 2015, pp. 801–818.e4. 8. jones jm, koski l, khan m, brady s, sunenshine r, komatsu kk. coccidioidomycosis: an underreported cause of death—arizona, 2008–2013. medical mycology. 2018;56(2):172-179. doi:10.1093/mmy/myx041 9. sweet’s syndrome associated with myelodysplasia: possible role of cytokines in the pathogenesis of the disease reuss‐borst 1993 british journal of haematology wiley online library. accessed june 19, 2020. https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1 365-2141.1993.tb03083.x 10. dicaudo dj, ortiz kj, mengden sj, lim kk. sweet syndrome (acute febrile neutrophilic dermatosis) associated with pulmonary coccidioidomycosis. arch dermatol. 2005;141(7). doi:10.1001/archderm.141.7.881 conclusion mailto:lshedlofsky@affderm.com https://doi.org/10.1016/j.ajem.2019.06.012 https://www.jaad.org/article/s0190-9622(94)70215-2/pdf https://www.jaad.org/article/s0190-9622(94)70215-2/pdf https://doi.org/10.1016/j.jaad.2017.09.013 https://doi.org/10.2165/00128071-200203020-00005 https://doi.org/10.1111/ijd.14159 https://doi.org/10.3389/fimmu.2019.00414 https://doi.org/10.1093/mmy/myx041 https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2141.1993.tb03083.x https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2141.1993.tb03083.x https://doi.org/10.1001/archderm.141.7.881 skin july 2019 volume 3 issue 4 copyright 2019 the national society for cutaneous medicine 283 compelling comments the father of modern cryotherapy caroline crain, bs1,jake alan gibbons, bsa1, tyler marion, b., mba1 1the university of texas medical branch school of medicine, galveston, tx cryotherapy, the destruction of living tissue through freezing, is extensively utilized in the modern practice of dermatology. its use dates back to the mid nineteenth century by dr. james arnott of england. born in 1797, arnott is widely regarded as the father of cryotherapy.1 he used a solution of crushed ice and salt, reaching temperatures as low as -24°c, to freeze tumors in patients with advanced cancers. this technique was useful in reducing tumor size, decreasing bleeding, and ameliorating pain.1 in his own words, dr. arnott described the significance of his work: “congelation arresting the accompanying inflammation, and destroying the vitality of the cancer cell, is not only calculated to prolong life for a great period, but may, not improbably, in the early stage of the disease, exert a curative action.”2 arnott designed his own cryotherapy device, which consisted of a cushion connected to two tubes that carried water from a reservoir containing the freezing salt solution. dr. arnott presented and won a medal for this device at the great exhibition of london in 1851.3 in addition to treating tumors, arnott also proposed that cryotherapy could be used to treat acne, neuralgia, and headaches due to the numbing effects of freezing temperatures. additionally, arnott suggested that the numbing effects of the cold should be further utilized to anesthetize skin prior to surgery.1 from arnott’s early work, the practice of cryotherapy has blossomed into a staple in the practice of modern dermatology. today, dermatologists use cryotherapy in the form of liquid nitrogen to treat cutaneous lesions. it has emerged as an inexpensive, safe, and easy way to treat skin lesions in a clinical setting. furthermore, cryotherapy provides great cosmetic results which is a significant upside for the practicing dermatologist. conflict of interest disclosures: none. funding: none. corresponding author: tyler marion, b.s., m.b.a. the university of texas medical branch, 301 university blvd, galveston, tx 77555 trmarion9@gmail.com references: 1. cooper sm, dawber rpr. the history of cryosurgery. journal of the royal society of medicine. 2001; 94(4):196-201. 2. arnott j. practical illustrations of the remedial efficacy of a very low or anesthetic temperature. i. in cancer. lancet. 1850; 2:257–259. 3. bird h. james arnott, md (aberdeen), 1797-1883, a pioneer in refrigeration. anaesthesia 1949; 4: 10-17. skin january 2019 volume 3 issue 1 copyright 2018 the national society for cutaneous medicine 24 research letter current curriculum on reflectance confocal microscopy: a national survey of dermatology faculty and residents jonathan m soh, md1, alice p pentland, md1 1department of dermatology, university of rochester medical center, rochester, ny reflectance confocal microscopy (rcm) is a non-invasive imaging modality used in dermatology since the 1990s.1,2 as its diagnostic accuracy and precision grew throughout the past decades, it gained category 1 current procedural terminology (cpt) codes (96931-96936) by centers for medicare and medicaid services in 2016.3 this has allowed reimbursement for dermatologists and dermatopathologists to procure, read and interpret images of various skin lesions. highlighting its growing utility, a recent citation search on pubmed.gov using “reflectance confocal microscopy skin” revealed 1 result in 1994 to 30 in 2010 to 116 citation results in 2016. we surveyed dermatology residency programs to explore the exposure trainees have to rcm. to our knowledge, this is the first study quantifying use of rcm in academic training programs. this observational study was exempt per institutional board review. the nine question survey, designed by a dermatology resident and attending, was distributed to the national email listserv of the association of dermatology professors (apd). (figure 1) this email group is composed of faculty members including program directors and chairs. within the email, faculty, fellows and residents were invited to anonymously participate. it was up to the discretion of the faculty member to distribute or forward the invitation on to his or her residents. the survey was open for 8 weeks with recruitment emails sent at week 0 and 4. survey design, distribution and analysis were similar to previously published studies assessing dermatology residency curriculum.4 descriptive statistics were used to characterize the survey responses. figure 1: survey questions. 1. what state is your training program in? 2. what is your role? • program director • other faculty • resident/fellow 3. how is reflectance confocal microscopy included within resident curriculum? • directly: faculty or industry led didactic that results in understanding of and experience in reading images. • indirectly: resident-led or self-learned through reading, videos, seminars, etc. • not-at-all: to best of your knowledge, rcm is not taught or learned in any meaningful capacity • other: 4. if answered “directly”, “indirectly” or “other” above, how often is reflectance confocal microscopy taught by either a faculty, fellow, resident or industry member? skin january 2019 volume 3 issue 1 copyright 2018 the national society for cutaneous medicine 25 • <1-3 times per week • 1-3 times per week • >1-3 times per week 5. how often is conventional dermatopathology (ie. traditional h&e slides) taught by a faculty, fellow, resident or industry member? • <1-3 times per week • 1-3 times per week • >1-3 times per week 6. does your program have clinical or research faculty who use rcm on a routine basis? • yes • no • unknown • other 7. is reflectance confocal microscopy reimbursable in your area? • yes • no • unknown • other 8. in the next 5 years, do you foresee a need to directly incorporate rcm into resident curriculum? • yes • no • unknown • other 9. comments during the 8-week period, 70 responses (40 residents, 29 faculty, 1 unspecified) were collected and outlined in table 1.the response rate amongst faculty was 6.6% (29/439). the resident response rate is unclear as there is no way to estimate how many residents the recruitment email was ultimately forwarded to. approximately 54% of respondents answered that rcm is not taught or learned table 1: survey responses. % demographics faculty 42 residents/fellows 58 how is rcm included within resident curriculum? directly: faculty or industry led didactic leading to understanding of and experience in reading images 29 indirectly: resident-led or self-learned through reading, videos, seminars 13 not-at-all: rcm not taught or learned in meaningful capacity 54 other 4 if answered "directly", "indirectly" or "other" above, how often is reflectance confocal microscopy taught by either a faculty, fellow, resident or industry member? <1-3 times per week 91 1-3 times per week 9 >1-3 times per week 0 how often is conventional dermatopathology (ie. traditional h&e slides) taught by a faculty, fellow, resident or industry member? <1-3 times per week 7 1-3 times per week 77 >1-3 times per week 16 does your program have clinical or research faculty who use reflectance confocal microscopy on a routine basis? yes 40 no 47 unknown 13 is reflectance confocal microscopy reimbursable in your area? yes 22 no 9 unknown 70 in the next 5 years, do you foresee a need to directly incorporate rcm into resident curriculum? yes 46 no 20 unknown 33 in a meaningful capacity. for those who received indirect or direct training in rcm, it was taught on average <1-3 times per week vs. an average 1-3 times per week for traditional dermatopathology. nearly 40% of skin january 2019 volume 3 issue 1 copyright 2018 the national society for cutaneous medicine 26 responses indicated that rcm is routinely used by faculty within clinical and research settings. about half of respondents stated a need to incorporate rcm within residency curriculum. the majority of respondents (70%) did not know if rcm was reimbursable. as rcm’s use becomes standardized and streamlined into clinical use,5,6 there may be a need to systematically train residents in the acquisition and interpretation of its images. this national survey is one of the first to characterize rcm’s current integration into residency education. the results suggest that despite a lack of formalized training, there is cautious optimism towards the modality’s usage in dermatologic practice. while the majority of responders envisioned a need to incorporate rcm into residency curriculum within 5 years, one-third of respondents were currently undecided about its importance. within the comments section of the survey, some respondents cited the time involved as an obstacle to rcm’s integration into daily work flow. highlighting the current use of rcm, 40% of responses indicated that faculty routinely integrate rcm into clinical and research settings. despite this popularity, there remains room for growth and education. only 22% of respondents knew that rcm was potentially reimbursable. the current reimbursement structure for rcm is based on a per-lesion basis (effective 1/1/2017). similar to traditional biopsy and pathology; rcm payment best approximates the time and effort that goes into acquiring and interpreting each lesion and is similar to that of traditional biopsy and pathology payments. as more dermatologists adopt rcm, the us centers for medicare and medicaid services will be able to redefine and match reimbursement with time involved.5 given the low faculty response rate, this study could be susceptible to a response bias where those interested in rcm may have responded favorably. therefore, while the results suggest an enthusiastic trend, we are cautious to generalize to the greater academic population at this time. our hope is that this and future studies can provide insight into the need for a standardized rcm curriculum. conflict of interest disclosures: none. funding: none. corresponding author: jonathan m. soh, md university of rochester medical center department of dermatology rochester, ny jonathan_soh@urmc.rochester.edu references: 1. federman d piérard ge. in vivo confocal microscopy: a new paradigm in dermatology. dermatology. 1993;186(1):45. http://www.ncbi.nlm.nih.gov/pubmed/84 35516. accessed september 3, 2017. 2. rajadhyaksha m, grossman m, esterowitz d, webb rh, rox anderson r. in vivo confocal scanning laser microscopy of human skin: melanin provides strong contrast. j invest dermatol. 1995;104(6):946-952. doi:10.1111/15231747.ep12606215 3. association am. cpt 2017 professional edition. 4th editio. chicago, il: american medical association; 2016. 4. burgin s, homayounfar g, newman lr, sullivan a. instruction in teaching and teaching opportunities for residents in us dermatology programs: results of a national survey. j am acad dermatol. 2017;76(4):703-706. doi:10.1016/j.jaad.2016.08.043 mailto:jonathan_soh@urmc.rochester.edu skin january 2019 volume 3 issue 1 copyright 2018 the national society for cutaneous medicine 27 5. rajadhyaksha m, marghoob a, rossi a, halpern ac, nehal ks. reflectance confocal microscopy of skin in vivo: from bench to bedside. lasers surg med. 2017. doi:10.1002/lsm.22600 6. hoogedoorn l, gerritsen mjp, wolberink eaw, peppelman m, van de kerkhof pcm, van erp pej. a four-phase strategy for the implementation of reflectance confocal microscopy in dermatology. j eur acad dermatology venereol. 2016;30(8):13081314. doi:10.1111/jdv.13627 poster presented at 13th annual winter clinical dermatology conference | maui, hi | january 12 17, 2018 open-label study (arido) evaluating long-term safety of topical glycopyrronium tosylate (gt) in patients with primary axillary hyperhidrosis dee anna glaser,1 adelaide a. hebert,2 alexander nast,3 william p. werschler,4 stephen shideler,5 lawrence green,6 richard d. mamelok,7 janice drew,8 john quiring,9 david m. pariser10 1saint louis university, st. louis, mo; 2uthealth mcgovern medical school, houston, tx; 3charité–universitätsmedizin berlin, berlin, germany; 4premier clinical research, spokane, wa; 5shideler dermatology and skin care center, carmel, in; 6george washington university school of medicine, washington, dc; 7mamelok consulting, palo alto, ca; 8dermira, inc., menlo park, ca; 9qst consultations, allendale, mi; 10eastern virginia medical school and virginia clinical research, inc., norfolk, va introduction • hyperhidrosis affects an estimated 4.8% of the us population, or approximately 15.3 million people,1 and the impact of hyperhidrosis on quality of life is reported as comparable to, or greater than, psoriasis or eczema2 • glycopyrronium tosylate (gt; formerly drm04) is a topical cholinergic receptor antagonist being developed for the treatment of primary axillary hyperhidrosis in patients ≥9 years of age • gt has been assessed in 2 replicate, randomized, double-blind, vehicle-controlled, pivotal phase 3 lead-in trials (atmos-1 and atmos-2) – gt was generally well tolerated and demonstrated clinically meaningful improvements in disease severity and reductions in sweat production through 4 weeks in these trials3 • arido (nct02553798) assessed the long-term safety of gt in a minimum of 100 patients with primary axillary hyperhidrosis treated for at least 12 months methods study design • arido was a 44-week, open-label extension of atmos-1 (nct02530281) and atmos-2 (nct02530294) (figure 1) • in atmos-1/atmos-2 patients with primary axillary hyperhidrosis were randomized 2:1 to gt (3.75% topical solution) or vehicle applied once daily to each axilla for 28 days (figure 1) • patients who completed atmos-1/atmos-2 with ≥80% treatment compliance were eligible to continue into arido and receive open-label gt for up to 44 weeks or until early termination, including patients terminated once the study objective of 100 patients receiving treatment for ≥12 months was achieved (figure 1) • key inclusion criteria for atmos-1/atmos-2 were: – ≥9 years of age (patients <16 years were recruited only at us sites) – primary axillary hyperhidrosis for ≥6 months – gravimetrically-measured sweat production of ≥50 mg/5 min in each axilla – axillary sweating daily diary (asdd; for patients ≥16 years of age) or asdd-children (asdd-c; for patients <16 years of age) axillary sweating severity item (item 2) 4 score ≥4 (0 to 10 numeric rating scale) – hyperhidrosis disease severity scale (hdss) ≥3 • key exclusion criteria for atmos-1/atmos-2 were: – history of a condition that could cause secondary hyperhidrosis – prior surgical procedure or treatment with a medical device for axillary hyperhidrosis – treatment with iontophoresis within 4 weeks or treatment with botulinum toxin within 1 year for axillary hyperhidrosis – axillary use of nonprescription antiperspirants within 1 week or prescription antiperspirants within 2 weeks – new or modified psychotherapeutic medication regimen within 2 weeks – treatment with medications having systemic anticholinergic activity, centrally acting alpha-2 adrenergic agonists, or beta-blockers within 4 weeks unless dose had been stable ≥4 months and was not expected to change – conditions that could be exacerbated by study medication figure 1. study design wk 0 randomization baselinea wk 4 wk 49 end of study screening double-blindtreatment 44-week open-label extension arido atmos-1 and atmos-2 target recruitment (both trials combined): 660 patients randomized 2:1 gt gt 564 (86.6%) patients continued into arido vehicle wk 48 abaseline for arido was week 0 of atmos-1/atmos-2 gt, topical glycopyrronium tosylate; wk, week assessments • primary objective was long-term safety – safety was evaluated via treatment-emergent adverse events (teaes) through week 45 (week 44 + 1 week safety follow-up), local skin reactions (lsrs) through week 44, laboratory testing, vital signs, and physical examinations – teaes are summarized overall from the first application of study drug in arido to week 45 • descriptive efficacy assessments evaluated in arido were an extension of the primary endpoints in atmos-1/atmos-2 – change from baseline in atmos-1/atmos-2 in gravimetrically-measured sweat production at week 44 (up to 48 weeks of gt) – change from baseline in atmos-1/atmos-2 in hdss responder rate (≥2-grade improvement) at week 44 (up to 48 weeks of gt) • all safety and efficacy analyses were performed on the safety population (patients receiving ≥1 dose of gt and having ≥1 post-baseline assessment in arido) results • the majority of patients (86.6%; n=564) completing atmos-1/atmos-2 (369 patients [65.4%] had received gt, and 195 [34.6%] had received vehicle) continued into arido (figure 2) • of the patients enrolled in arido, most patients were female (55.3%) and white (83.3%) with a mean age of 33.0 years and mean bmi of 27.3 kg/m2 (table 1) • the trial was terminated, per protocol, once study objectives were reached – a total of 226 patients completed 44 weeks of treatment figure 2. patient disposition gt n=426 n=332 (58.9%) gt n=564a (86.6%) n=226 (40.1%) vehicle n=225 completed 44 weeks completed atmos-1 and atmos-2n=651 gt n=369 vehicle n=195 entered arido discontinued due to: lost to follow-up consent withdrawn adverse event noncompliance pregnancy protocol violation physician decision (16.3%) (14.5%) (7.8%) (1.4%) (0.5%) (0.4%) (0.2%) 92 82 44 8 3 2 1 discontinued due to: study objectives met/ study terminatedb 106 (18.8%) a14 patients in arido did not have a post-baseline assessment and were therefore excluded from the safety population bsponsor terminated study early, per protocol, when study objective of 100 patients receiving treatment for at least 12 months was achieved gt, topical glycopyrronium tosylate table 1. demographics and baselinea disease characteristics (safety populationb) gt (n=550) demographics age (years), mean ± sd 33.0 ± 11.4 age group, n (%) ≥16 years <16 years 522 (94.9) 28 ( 5.1) female, n (%) 304 (55.3) white, n (%) 458 (83.3) bmi (kg/m2), mean ± sd 27.3 ± 5.0 baseline disease characteristics sweat production (mg/5 min), c mean ± sd 164.7 ± 145.0 hdss,d,e n (%) grade 3 grade 4 348 (63.3) 201 (36.5) quality of life dlqi,f mean ± sd cdlqi,g mean ± sd 11.4 ± 5.9 8.9 ± 5.4 abaseline in atmos-1/atmos-2 bpatients receiving ≥1 dose of gt and having ≥1 post-baseline assessment in arido cgravimetrically-measured average from the left and right axillae dhdss ≥3 was an inclusion criteria en=549; 1 subject entered atmos-2 with hdss=2, which was a protocol violation fpatients >16 years of age gpatients ≤16 years of age bmi, body mass index; cdlqi, children’s dlqi; dlqi, dermatology life quality index; gt, topical glycopyrronium tosylate; hdss, hyperhidrosis disease severity scale; sd, standard deviation efficacy assessments • through week 44/et in arido (up to 48 weeks of gt), gt-treated patients continued to demonstrate improvements in efficacy measures, including sweat production and hdss responder rate (figure 3) – from baseline in atmos-1/atmos-2 to week 44/et in arido, mean sweat production decreased by 95.7 ± 140.8 mg/5 min, which was maintained from a decrease of 107.6 ± 207.2 mg/5 min in gt-treated patients after 4 weeks in atmos-1/atmos-2 (figure 3a) – at week 44/et in arido, hdss responder rate (≥2-grade improvement) was 63.2%, a further improvement from 59.1% in gt-treated patients at week 4 in atmos-1/atmos-2 • hdss grade improved by 1, 2, and 3 grades in 30.9%, 46.7%, and 16.5% of patients, respectively (figure 3b) figure 3. mean sweat production and hdss improvement from baselinea to week 44/et (safety populationb) baseline (n=550) 164.7 week 44/et (n=430) 63.1 mean cfb: -95.7 ± 140.8 none 5.9% 1 grade 30.9% 2 grades 46.7% 3 grades 16.5% improvement 350 300 250 200 150 100 50 -100 -50 0 m ea n s w ea t p ro du ct io n (m g/ 5 m in ) a. sweat productionc 100 80 60 40 20 0 p ro po rt io n of s ub je ct s (% ) b. hdss improvementd abaseline in atmos-1/atmos-2 bpatients receiving ≥1 dose of gt and having ≥1 post-baseline assessment in arido cgravimetrically-measured average from the left and right axillae dn=437 cfb, change from baseline; et, early termination; hdss, hyperhidrosis disease severity scale safety assessments • after 44 weeks, 329 (59.8%) patients reported ≥1 teae, though most were mild or moderate in severity (table 2) • a total of 44 (8.0%) patients discontinued due to a teae and 7 (1.3%) reported ≥1 serious teae (table 2) • prespecified anticholinergic teaes of interest were reported in 78 (14.2%) patients; most were mild or moderate in severity and were able to be managed by dose interruption (table 2) – 37 patients reported 45 vision blurred events; 40 (88.9%) were bilateral – 29 patients reported 37 mydriasis events; 31 (83.8%) were unilateral • generally, teaes, including teaes prespecified as anticholinergic teaes of interest, did not increase over time with longer duration of exposure (table 3) • 179 (32.5%) of patients reported lsrs, which were typically mild or moderate in severity (figure 4) • there were no clinically meaningful changes in laboratory parameters or vital signs table 2. summary of treatment-emergent adverse events from baselinea to week 45/et (safety populationb) gt (n=550) any teae, n (%) 329 (59.8) any serious teae, n (%) 7 ( 1.3)c discontinuation due to a teae, n (%) 44 ( 8.0) deaths, n (%) 0 most frequently reported teaes (>5% patients), n (%) dry mouth vision blurred application site pain nasopharyngitis mydriasis 93 (16.9) 37 ( 6.7) 35 ( 6.4) 32 ( 5.8) 29 ( 5.3) prespecified anticholinergic teaes of interest, n (%) vision blurred mydriasis urinary hesitation nocturia urine flow decreased hypermetropia pollakiuria pupils unequal 78 (14.2) 37 ( 6.7)d 29 ( 5.3)e 23 ( 4.2) 2 ( 0.4) 2 ( 0.4) 1 ( 0.2) 1 ( 0.2) 1 ( 0.2) any teaes (n=329) teaes by severity, n (%) mild moderate severe 148 (45.0) 153 (46.5) 28 ( 8.5) relation to study drug, n (%) not related related 131 (39.8) 198 (60.2) numbers in table represent the number of patients reporting ≥1 teae, not number of events ateaes are those with an onset after first application of study drug in arido bpatients receiving ≥1 dose of gt and having ≥1 post-baseline assessment in arido cinfectious colitis, affective disorder, suicide attempt, mydriasis, chest pain, concussion, diverticulitis d37 patients reported 45 vision blurred events; 40 (88.9%) were bilateral e29 patients reported 37 mydriasis events; 31 (83.8%) were unilateral et, early termination; gt, topical glycopyrronium tosylate; teae, treatment-emergent adverse event table 3. summary of frequently reported teaes and teaes of special interest (safety populationa) teaes, n (%) duration of exposure 0 to 4 weeks (n=550) >4 to 8 weeks (n=537) >8 to 20 weeks (n=479) >24 to 36 weeks (n=417) >36 weeks to es (n=365) any teae 176 (32.0) 148 (27.6) 102 (21.3) 78 (18.7) 59 (16.2) teaes reported in >5% of patients dry mouth vision blurred application site pain nasopharyngitis mydriasis 59 (10.7) 11 ( 2.0) 16 ( 2.9) 14 ( 2.5) 8 ( 1.5) 23 ( 4.3) 14 ( 2.6) 9 ( 1.7) 9 ( 1.7) 8 ( 1.5) 19 ( 4.0) 7 ( 1.5) 5 ( 1.0) 4 ( 0.8) 9 ( 1.9) 15 ( 3.6) 5 ( 1.2) 6 ( 1.4) 5 ( 1.2) 5 ( 1.2) 5 ( 1.4) 4 ( 1.1) 3 ( 0.8) 3 ( 0.8) 2 ( 0.5) prespecified anticholinergic teaes of interest vision blurred mydriasis urinary hesitation nocturia urine flow decreased hypermetropia pollakiuria pupils unequal 11 ( 2.0) 8 ( 1.5) 14 ( 2.5) 2 ( 0.4) 1 ( 0.2) 0 0 1 ( 0.2) 14 ( 2.6) 8 ( 1.5) 4 ( 0.7) 0 1 ( 0.2) 0 0 0 7 ( 1.5) 9 ( 1.9) 4 ( 0.8) 0 0 0 0 0 5 ( 1.2) 5 ( 1.2) 2 ( 0.5) 0 0 1 ( 0.2) 1 ( 0.2) 0 4 ( 1.1) 2 ( 0.5) 1 ( 0.3) 0 0 0 0 0 numbers in table represent the number of patients reporting ≥1 teae, not number of events teaes are those with an onset after first application of study drug in arido apatients receiving ≥1 dose of gt and having ≥1 post baseline assessment on arido es, end of study; gt, topical glycopyrronium tosylate; teae, treatment-emergent adverse event figure 4. summary of local skin reactions by severity from baselinea to week 44/et (safety populationb) any (n=179) 44 (25%) 120 (67%) 15 (8%) erythema (n=116) 27 (23%) 81 (70%) 8 (7%) burning/stinging (n=73) 24 (33%) 42 (58%) 7 (10%) pruritus (n=68) 26 (38%) 31 (46%) 11 (16%) dryness (n=48) 8 (17%) 39 (81%) 1 (2%) edema (n=34) 8 (24%) 24 (71%) 2 (6%) scaling (n=25) 5 (20%) 20 (80%) mild moderate severe 200 160 120 80 40 0 n um be r of l s r s patients were counted as having an lsr if any post-baseline assessment was mild, moderate, or severe abaseline in atmos-1/atmos-2 bpatients receiving ≥1 dose of gt and having ≥1 post-baseline assessment in arido et, early termination; gt, topical glycopyrronium tosylate; lsr, local skin reaction conclusions • safety results were consistent with anticholinergic treatment and with the safety profile observed in prior gt studies,3 with no new or unexpected findings – most teaes were mild or moderate in severity and considered by the investigator to be related to study drug – a low number of subjects discontinued due to a teae – while approximately one-third of patients reported local skin reactions, most were mild or moderate in severity – incidence of teaes, including prespecified anticholinergic teaes of interest, did not increase with long-term treatment • efficacy measures obtained at the end of treatment in arido indicated that subjects had maintained sweat production reduction and less bothersome sweating compared with baseline in atmos-1/atmos-2 • gt was generally well tolerated and improvements in efficacy measures were maintained in patients with primary axillary hyperhidrosis when applied once daily to both axillae over a maximum of 48 weeks references 1. doolittle et al. arch dermatol res. 2016;308(10):743-9. 2. hamm. dermatol clin. 2014;32(4):467-76. 3. pariser et al. poster presented at: 25th european academy of dermatology and venerology congress; september 28-october 2, 2016; vienna, austria. 4. glaser et al. poster presented at: 13th maui derm for dermatologists congress; march 20-24, 2017; maui, hi. acknowledgements this study was funded by dermira, inc. medical writing support was provided by prescott medical communications group (chicago, il). all costs associated with development of this poster were funded by dermira, inc. author disclosures dag: consultant and investigator for dermira, inc. aah: consultant for dermira, inc.; employee of the university of texas medical school, houston, which received compensation from dermira, inc. for study participation. an: employee of charité – universitätsmedizin berlin, which received compensation from dermira, inc. for study participation. wpw: consultant and investigator for dermira, inc. ss: investigator for dermira, inc. lg: consultant and investigator for dermira, inc.; investigator for brickell. rdm: consultant for dermira, inc. jd: employee of dermira, inc. jq: employee of qst consultations. dmp: consultant and investigator for dermira, inc. abstract • introduction: an increased incidence of cardiovascular (cv) events has been reported in psoriasis subjects. secukinumab, a fully human monoclonal antibody that selectively neutralizes il-17a, has significant efficacy in moderate-to-severe psoriasis and psoriatic arthritis. carima explored the effect of secukinumab on cv risk markers in psoriasis. • methods: carima was a 52-week, multicenter, exploratory, randomized, double-blind, placebo-controlled trial (nct02559622). subjects with moderate-to-severe plaque psoriasis but without manifest cv diseases were eligible. the primary outcome measure was endothelial function, a marker of early atherosclerosis, measured by flow-mediated dilation (fmd). • results: 151 subjects (mean age 45 years, 68% male) were randomized. of these, 48 and 54 subjects received 300 mg and 150 mg secukinumab, respectively and 26 and 23 subjects received placebo followed by 300 mg or 150 mg secukinumab, respectively. a baseline fmd (mean±sd) of 4.6% (±3.5), 4.6% (±4.6), 3.9% (±3.9), and 3.7% (±3.2) was observed for subjects assigned to 300 or 150 mg secukinumab or placebo followed by 300 mg or 150 mg secukinumab. at week 12, the baseline-adjusted fmd showed a numerically larger improvement in subjects receiving 300 mg secukinumab vs. the pooled placebo group (δ = 1.2%, ci [-0.7; 3.1], p=0.223) than in subjects receiving 150 mg secukinumab vs. the pooled placebo group (δ = 0.8%, ci [-1.0; 2.6], p=0.403). at week 52, fmd was increased by 2.1% in subjects receiving 300 mg secukinumab (ci [0.8; 3.3], p=0.002) and by 2.1% in subjects receiving 150 mg secukinumab (ci [0.7; 3.4], p=0.003) vs. baseline. there were no deaths and no myocardial infarctions in the study. there was one case of a cerebral infarction, which was not suspected to be related to study medication. • conclusions: although subjects with established cv diseases were excluded, the comparably large carima study population confirmed earlier findings of endothelial dysfunction associated with subclinical atherosclerosis in psoriasis. a numerical, clinically meaningful improvement of fmd was observed after 12 weeks (secukinumab 300 mg). the difference reached statistical significance after 52 weeks (150 and 300 mg). the safety profile of secukinumab was comparable to prior studies and there were no new safety signals. secukinumab may improve endothelial function, which could help to prevent cardiovascular disease progression in psoriatic subjects. introduction • an increased incidence of cv events has been reported in psoriasis patients • this comorbidity could be the result of a prolonged subclinical systemic inflammatory response • secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin (il)-17a, has shown significant efficacy in the treatment of moderate-to-severe psoriasis and psoriatic arthritis, demonstrating a rapid onset of action and sustained response with a favorable safety profile1 • previous studies have shown that a 1% increase in fmd corresponds to a 13% relative cv risk reduction2 • carima aimed to explore the effect of secukinumab on cv risk markers in psoriasis patients methods • carima was a multicenter, exploratory, interdisciplinary, randomized, double-blind, placebo-controlled trial (nct02559622). only subjects with moderate-to-severe plaque psoriasis and without known severe cv diseases were eligible • they were randomized in a 2:2:1:1 ratio to 300 mg or 150 mg secukinumab until week 52 or to placebo until week 12 followed by 300 mg or 150 mg secukinumab until week 52. placebo groups were pooled for week 12 comparisons • the primary outcome measure was endothelial function, a marker of early atherosclerosis, measured by fmd • experienced sonographers were trained and certified to measure fmd using a standard protocol, equipment, and software. fmd values of 49 volunteers (not study subjects) were acquired twice on the same day to assess reproducibility • the subject’s arm was immobilized using a pneumatic pillow and brachial artery diameter was measured at rest (1 minute), during inflation of the distal cuff to 220 mmhg for 5 minutes and for 4 minutes following deflation. fmd was measured as the % maximal increase in diameter following deflation of the cuff • data were assessed by cardiologists at a reading center for quality control and blinded evaluation of results secukinumab 150 mg (wk 12 and q4wk) secukinumab 300 mg (wk 12 and q4wk) secukinumab 150 mg (bsl; wk 1, 2, 3, 4, 8) secukinumab 300 mg (bsl; wk 1, 2, 3, 4, 8) week 52week 12 placebo (bsl; wk 1, 2, 3, 4, 8) baseline secukinumab 150 mg (wk 12, 13, 14, 15, 16, 20 and q4wk) secukinumab 300 mg (wk 12, 13, 14, 15, 16, 20 and q4wk) placebo (bsl; wk 1, 2, 3, 4, 8) oitar noitazi modna r 2 : 2 : 1 1 : figure 1. carima study design results table 1. baseline demographic and disease characteristics characteristic a. sec 300 mg (n = 48) b. sec 150 mg (n = 54) c. pbo – sec 300 mg (n = 26) d. pbo – sec 150 mg (n = 23) mean age, years (sd) 44.2 (12.9) 46.0 (14.4) 43.7 (11.4) 46.8 (13.1) male gender, n (%) 37 (77.1) 31 (57.4) 18 (69.2) 16 (69.6) body weight (kg), mean (sd) 86.5 (15.3) 84.4 (19.3) 95.4 (26.0) 89.8 (22.0) bmi (kg/m2) 27.8 28.1 30.1 29.7 baseline pasi, mean (sd) 19.3 (7.9) 21.7 (10.5) 17.5 (4.2) 19.5 (6.1) mean time since psoriasis diagnosis, years (sd) 20.6 (12.7) 20.8 (13.3) 18.9 (11.7) 20.3 (11.7) psoriatic arthritis reported, n (%) 12 (25.0) 15 (27.8) 4 (15.4) 4 (17.4) prior non-biologic, systemic therapy, n (%) 43 (89.6) 46 (85.2) 24 (92.3) 16 (69.6) prior biologic therapy, n (%) 15 (31.3) 20 (37.0) 8 (30.8) 9 (39.1) diabetes, n (%) 4 (8.3) 9 (16.7) 3 (11.5) – dyslipidemia / hyperlipidemia, n (%) 3 (6.3) 3 (5.6) 5 (19.2) 1 (4.3) hypertension, n (%) 13 (27.1) 14 (25.9) 9 (34.6) 7 (30.4) smoking status, n (%) never 19 (39.6) 21 (38.9) 11 (42.3) 9 (39.1) smoking status, n (%) former 9 (18.8) 11 (20.4) 3 (11.5) 7 (30.4) smoking status, n (%) current 20 (41.7) 22 (40.7) 12 (46.2) 7 (30.4) bmi, body mass index; pasi, psoriasis area and severity index; pbo, placebo; sd, standard deviation; sec, secukinumab • at week 12, the baseline-adjusted fmd showed a numerically larger improvement in subjects receiving 300 mg secukinumab vs. the pooled placebo group (δ = 1.2%, ci [-0.7; 3.1], p=0.223) than in subjects receiving 150 mg secukinumab vs. the pooled placebo group (δ = 0.8%, ci [-1.0; 2.6], p=0.403) • there were no deaths and no myocardial infarctions in the study up to week 52 • there was one case of a cerebral infarction after surgery for ovarian cancer in a 67-year-old hypertensive subject who had received 150 mg secukinumab for 94 days, which was not suspected to be related to the study medication 4.4% 6.1% 0.0% 2.0% 4.0% 6.0% 8.0% 10.0% psoriasis patients total study population n = 132 volunteers for studysite fmd training not treated in the study n = 49 figure 2. baseline fmd 0.5% 2.1% 0.1% 2.1% -0.1% 2.2% 0.1% 1.2% -3.0% -2.0% -1.0% 0.0% 1.0% 2.0% 3.0% 4.0% 5.0% sec 300 mg week 12 n = 39 sec 300 mg week 52 n = 38 sec 150 mg week 12 n = 48 sec 150 mg week 52 n = 43 pbo sec 300 mg week 12 n = 21 pbo sec 300 mg week 52 n = 20 pbo sec 150 mg week 12 n = 17 pbo sec 150 mg week 52 n = 17 * * ns ns ns ns ns ns figure 3. fmd change vs. baseline conclusions • although subjects with known severe cv diseases were excluded, the comparably large carima study population confirmed earlier findings of endothelial dysfunction associated with subclinical atherosclerosis in psoriasis subjects • the safety profile of secukinumab was comparable to prior studies and there were no new safety signals • a numerical, but clinically meaningful, improvement in fmd (> 1%) was observed after 12 weeks (secukinumab 300 mg). the difference reached statistical significance after 52 weeks (150 and 300 mg) • the carima study results indicate that secukinumab may improve endothelial function, thereby reducing cv disease progression in psoriatic subjects bsl, baseline; q4wk, every 4 weeks; wk, week. adjusted mean improvement vs. baseline +/confidence interval. *p<0.01; ns: nonsignificant fmd, flow-mediated dilation; pbo, placebo; sec, secukinumab mean +/standard deviation fmd, flow-mediated dilation secukinumab reduces endothelial dysfunction in subjects with moderate-to-severe plaque psoriasis over 52 weeks: results of the exploratory carima study e von stebut1, k reich2, d thaçi3, w koenig4, a pinter5, a körber6, t rassaf7, a waisman1, v mani8, d yates9, j frueh10, c sieder11, n melzer11, t gori1 1university medical center mainz, mainz, germany; 2dermatologikum hamburg and sciderm research institute, hamburg, germany; 3university hospital schleswig-holstein, lübeck, germany; 4university of ulm medical center, ulm, germany, deutsches herzzentrum münchen, technische universität münchen, munich, germany; 5university hospital frankfurt, frankfurt, germany; 6university hospital essen, essen, germany; 7west-german heart and vascular center, university hospital essen, essen, germany; 8icahn school of medicine at mount sinai, new york, ny, usa; 9novartis institutes for biomedical research, cambridge, ma, usa; 10novartis pharma ag, basel, switzerland; 11novartis pharma gmbh, nürnberg, germany download document at the following url: http://novartis.medicalcongressposters.com/default.aspx?doc=19d4f and via text message (sms) text: q19d4f to: 8nova (86682) us only +18324604729 north, central and south americas; caribbean; china +447860024038 uk, europe & russia +46737494608 sweden, europe scan to download a reprint of this poster references 1. langley rg et al. n engl j med. 2014;371:326-338. 2. inaba y et al. int j cardiovasc imaging. 2010;26:631-640. disclosures e von stebut: honoraria from novartis. k reich: advisor and/or paid speaker for and/or participated in clinical trials sponsored by abbvie, amgen, biogen, boehringer-ingelheim, celgene, centocor, covagen, forward pharma, glaxosmithkline, janssen-cilag, leo, lilly, medac, merck sharp & dohme corp., novartis, ocean pharma, pfizer, regeneron, takeda, ucb pharma, xenoport. d thaçi: honoraria from abbvie, amgen, almirall biogen idec, celgene, dignity, lilly, galapagos, glaxosmithkline, janssen-cilag, leo pharma, maruho, mitsubishi, msd, novartis, pfizer, regeneron, sanofi, ucb, xenoport. w koenig: honoraria from pfizer, astrazeneca, novartis, the medicines company, dalcor, sanofi, berlin-chemie, kowa, amgen; grants and nonfinancial support from roche diagnostics, beckmann, singulex, abbott. all outside the submitted work. a pinter: honoraria from abbvie, amgen, biogen-idec, bms, celgene, lilly, janssen-cilag, leo pharma, merck, novartis, pfizer, regeneron, roche. a körber: honoraria from celgene, lilly, janssen-cilag, leo pharma, novartis, pfizer, almirall, grünenthal, abbvie, msd, ucb. t rassaf: honoraria from astrazeneca and bayer ag. a waisman: honoraria from novartis. v mani: grant support from aegerion, amgen, novartis, daiichi sankyo; honoraria from aegerion; consultant for tursiop inc. and medlion inc. d yates, j frueh, c sieder, and n melzer: employees of novartis. t gori: honoraria from novartis, abbott vascular/st jude, bayer, daiichi-sankyo, boehringer-ingelheim, volcano, astrazeneca, bms, stentys. acknowledgements the authors thank the patients and their families and all investigators and their staff for participation in the study. oxford pharmagenesis, inc., newtown, pa, usa, provided assistance with layout and printing the poster; this support was funded by novartis pharmaceuticals corporation, east hanover, nj. the authors had full control of the contents of this poster. this research was sponsored by novartis pharma gmbh, nuremberg, germany. originally presented at: 26th annual congress of the european academy of dermatology and venereology, geneva, switzerland; september 13–17, 2017. poster presented at: 13th annual winter clinical dermatology conference, maui, hi, usa; january 12–17, 2018. 2:1 randomization washout of tcs and other ad medication 300 mg q2w after initial loading dose (600 mg) clinical response defined as iga-0/1 or easi-75 tralokinumab q2w  tcs (n=69) 16-week responders tralokinumab q4w  tcs (n=69) 1:1 re-randomization tralokinumab q2w  tcs (n=95) 16-week non-responders placebo q2w  tcs (n=41) 16-week responders tralokinumab q2w  tcs (n=79) 16-week non-responders screening initial treatment continuation treatment safety follow-up o�-treatment period 46 weeks32 weeks16 weeks0-6 weeks tralokinumab q2w  tcs placebo q2w  tcs n-253 n=127 figure 1. study design of the ecztra 3 trial 193.5 g 134.9 g 250 200 150 100 50 0 0 2 4 6 8 10 12 14 16 week c u m u la ti ve a m o u n t o f tc s , g placebo q2w  tcs (n=126) tralokinumab q2w  tcs (n=252) * * ** ** figure 3. the cumulative amount of tcs used through week 16 56.0% 35.7% iga-0/160 50 40 30 20 10 0 a b easi-75 0 2 4 6 8 10 12 14 16 week ig a -0 /1 , % 60 50 40 30 20 10 0 ea s i75 , % placebo q2w  tcs (n=126) tralokinumab q2w  tcs (n=252) placebo q2w  tcs (n=126) tralokinumab q2w  tcs (n=252) 0 2 4 6 8 10 12 14 16 week * ** *** *** *** ## * # 38.9% 26.2% figure 2. proportion of patients receiving placebo q2w plus tcs or tralokinumab q2w plus tcs who achieved a an iga score of 0 (clear) or 1 (almost clear) skin and b) a 75% improvement in easi score over the 16-week initial treatment period worst daily pruritus nrs reduction ��4 100 50 60 70 80 90 40 30 20 10 0 a p a ti e n ts , % placebo q2w � tcs (n=126) tralokinumab q2w � tcs (n=249) 45.4% 34.1% * dlqi 0 –10 –5 –15 –20 c a d ju st e d m e a n c h a n g e fr o m b a se lin e placebo q2w � tcs (n=126) tralokinumab q2w � tcs (n=252) –8.8 –11.7 ** scorad 0 –50 –40 –30 –20 –10 –60 –70 b a d ju st e d m e a n c h a n g e fr o m b a se lin e placebo q2w � tcs (n=126) tralokinumab q2w � tcs (n=252) –26.8 –37.7 ** figure 4. a) percentage of patients with a reduction in worst daily pruritus nrs (weekly average) 4, b) adjusted mean change from baseline in scorad, c) adjusted mean change from baseline in dlqi 32.9% 21.4% 79.4% 57.9% easi-50 60 50 70 80 40 30 20 10 0 a b easi-90 0 2 4 6 8 10 12 14 16 week ea s i50 , % 60 50 40 30 20 10 0 ea s i90 , % placebo q2w  tcs (n=126) tralokinumab q2w  tcs (n=252) 0 2 4 6 8 10 12 14 16 week * * ** ** * * ** ** *** * *** *** *** figure 5. the proportion of patients achieving the additional secondary endpoints at week 16: a) at least a 50% reduction in easi score and b) at least a 90% reduction in easi score 100 50 60 70 80 90 40 30 20 10 0 a r e sp o n d e rs , % tralokinumab q2w  tcs/ q2w  tcs tralokinumab q2w  tcs/ q4w  tcs initial/ continuation treatment n/n 43/48 38/49 62/67 59/65 iga-0/1 easi-75 60 50 40 30 20 10 0 b r e sp o n d e rs , % 29/95b patients 53/95b patients iga-0/1 easi-75 89.6% 77.6% 30.5% 55.8% 92.5% 90.8% figure 6. treatment response after continuation of treatment for a further 16 weeks: a) proportion of tralokinumab q2w plus tcs responders (iga-0/1 and easi-75) at week 16a who maintained their clinical response at week 32 when receiving tralokinumab q2w plus tcs or q4w plus tcs and b) proportion of patients who became iga-0/1 or easi-75 responders at week 32 after continued treatment with tralokinumab q2w plus tcs introduction results methods objective ● the objective of the ecztra 3 trial (nct03363854) was to evaluate the efficacy and safety of tralokinumab in combination with tcs, compared with placebo in combination with tcs, in treating patients with moderate-to severe ad for up to 32 weeks. the ecztra 1 (nct03131648) and ecztra 2 (nct03160885) trials, described elsewhere, assessed tralokinumab monotherapy placebo q2w  tcs (n=127) tralokinumab q2w 1 tcs (n=253) table 1. patient demographics and disease characteristics at baseline n (%), week 16 placebo q2w 1 tcs(n=126) tralokinumab q2w 1 tcs (n=252) table 2. summary of adverse events in the initial 16-week treatment period conclusions ● all primary and secondary endpoints at week 16 demonstrated superiority of tralokinumab 300 mg q2w plus tcs compared with placebo q2w plus tcs ● approximately 90% of patients treated with tralokinumab q2w plus tcs who responded at week 16 maintained their response at week 32 with tralokinumab q2w plus tcs ● less frequent (q4w) dosing of tralokinumab could be appropriate in some patients ● less tcs was used by tralokinumab-treated patients compared with those who received placebo through the initial 16-week treatment period ● continued treatment with tralokinumab q2w plus tcs improved the initial response in many patients beyond 16 weeks ● the overall frequency of adverse events was comparable across treatment groups and did not increase with prolonged treatment efficacy and safety of tralokinumab plus concomitant topical corticosteroids in adult patients with moderate-to-severe atopic dermatitis: results from the 32-week, phase 3 ecztra 3 trial stephan weidinger,1 jonathan i. silverberg,2 darryl toth,3 thomas bieber,4 andrew f. alexis,5 boni e. elewski,6 andrew e. pink,7 dirkjan hijnen8 1department of dermatology and allergy, university hospital schleswig-holstein, kiel, germany; 2department of dermatology, the george washington university school of medicine and health sciences, washington, dc, usa; 3xlr8 medical research and probity medical research, windsor, on, canada; 4department of dermatology and allergy, university medical center, bonn, germany; 5department of dermatology, icahn school of medicine at mount sinai, new york, ny, usa; 6department of dermatology, university of alabama, birmingham, al, usa; 7st. john’s institute of dermatology, guy’s and st. thomas’ hospitals, london, uk; 8department of dermatology, erasmus university medical center, rotterdam, the netherlands ● atopic dermatitis (ad) is a chronic inflammatory skin disease1,2 characterized by eczematous lesions and multiple symptoms including pruritus, sleep disturbance, and depression.3-5 the type 2 cytokine, interleukin (il)-13, is a key driver of the underlying inflammation of ad and is overexpressed in lesional and non-lesional ad skin6,7 ● topical corticosteroids (tcs) are the current mainstay of therapy for ad, but tcs alone are often inadequate for the treatment of moderate-to-severe ad. in addition, prolonged use of tcs may cause unwanted adverse effects8,9 ● tralokinumab, a first-in-class, fully human monoclonal antibody, is designed to neutralize il-13, specifically inhibiting downstream il-13 signaling and thereby preventing pro-inflammatory activity6,7,10 patients ● eligible patients were 18 years of age with a confirmed diagnosis of ad for 1 year and with an inadequate response to treatment with topical medications. additional eligibility requirements included an ad body surface area involvement of 10%, eczema area and severity index (easi) of 12 at screening and 16 at baseline, investigator’s global assessment (iga) score of 3, and worst daily pruritus numeric racing scale (nrs) of 4 prior to baseline study design ● patients were randomized 2:1 to receive either subcutaneous tralokinumab 300 mg every 2 weeks (q2w) plus tcs or placebo q2w plus tcs over an initial treatment period of 16 weeks (figure 1) 2020 fall clinical dermatology conference, october 29-november 1, 2020, live virtual meeting patient characteristics ● a total of 380 patients were randomized to receive either tralokinumab q2w plus tcs (n=253) or placebo q2w plus tcs (n=127) over the initial 16-week treatment period ● baseline demographics and disease characteristics were similar across both treatment groups (table 1). patients had a long duration of ad prior to being enrolled into the study, with nearly half of patients experiencing severe ad (iga-4) at baseline aincludes usa and canada; bincludes belgium, germany, netherlands, poland, spain, and uk. primary endpoints ● at week 16, more patients achieved an iga-0/1 and easi-75 with tralokinumab q2w plus tcs compared with placebo q2w plus tcs (p0.05 and p0.001, respectively) (figure 2) *p0.05 versus placebo plus tcs; **p0.01 versus placebo plus tcs; ***p0.001 versus placebo plus tcs. model-based treatment difference: #p0.05 versus placebo plus tcs; ##p0.001 versus placebo plus tcs. composite estimand (primary analysis): patients who received rescue medication considered non-responders; patients with missing data imputed as non-responders. ● the cumulative amount of tcs used through to week 16 was lower with tralokinumab q2w plus tcs (134.9 g) compared with placebo q2w plus tcs (193.5 g; p0.01) (figure 3) ● use of rescue treatment, which included higher potency tcs or systemic treatment for ad, was reported by 2.8% of patients in the tralokinumab q2w plus tcs group and 10.2% of those in the placebo q2w plus tcs group *p0.05 versus placebo plus tcs; **p0.01 versus placebo plus tcs. assuming no nonreturned tubes were used. data collected after permanent discontinuation of investigational medicinal product or initiation of rescue medication not included. repeated measurements model: tcs (g) = treatment*week  region  baseline iga. secondary endpoints ● tralokinumab q2w plus tcs significantly improved outcomes for all key secondary endpoints (figure 4) ● a greater percentage of patients treated with tralokinumab q2w plus tcs had a reduction in worst daily pruritus nrs (weekly average) 4 at week 16 compared with placebo q2w plus tcs (p=0.037) (figure 4a) ● patients treated with tralokinumab q2w plus tcs also had a greater mean change from baseline in scorad and dlq compared with those who received placebo q2w plus tcs (both p0.001) (figures 4b and 4c) *p=0.037 versus placebo q2w plus tcs; **p0.001 versus placebo q2w plus tcs. adata collected after permanent discontinuation of investigational medicinal product or initiation of rescue medication not included. repeated measurements model on postbaseline data: change = treatment* week  baseline*week  region  baseline iga. in case of no postbaseline assessments before initiation of rescue medication, the week 2 change is imputed as 0; bmean across multiple imputations where applicable. patients who received rescue medication considered non-responders. patients with missing data at week 16 imputed as non-responders. single imputation analyses: cochran-mantel-haenszel test, stratified by region and baseline iga. multiple imputation analyses: combined inference from multiple mantel-haenszel risk differences and associated se. number of patients (n) based on patients in full analysis set with a baseline pruritus nrs weekly average of at least 4. ● more patients treated with tralokinumab q2w plus tcs achieved the additional secondary endpoints of easi-50 and easi-90 at week 16 compared with those who received placebo q2w plus tcs (figure 5) *p0.05 versus placebo plus tcs; **p0.01 versus placebo plus tcs; ***p0.001 versus placebo plus tcs. patients with missing data imputed as non-responders. aanalysis of patients who achieved a clinical response with tralokinumab q2w plus tcs at week 16 and were re-randomized to receive either tralokinumab q2w plus tcs or tralokinumab q4w plus tcs until week 32; bof the 95 patients who received tralokinumab q2w plus tcs as initial treatment and were assigned to the tralokinumab non-responder group, seven were mis-assigned: one achieved easi-75 and iga-0/1, and six achieved easi-75. continuation endpoints ● a clinical response with tralokinumab q2w plus tcs was maintained at week 32 in patients who achieved a response at week 16 (figure 6a) ● some patients who did not achieve iga-0/1 or easi-75 at week 16 were found to improve their iga-0/1 or easi-75 scores with continued tralokinumab q2w plus tcs treatment up to week 32 (figure 6b) safety ● tralokinumab in combination with tcs was well tolerated in patients with moderate-to-severe ad (table 2) ● the safety profile at week 32 was comparable with the initial 16-week treatment period ● tralokinumab plus tcs was associated with lower rates of severe and serious infections and eczema herpeticum compared with placebo plus tcs ● all conjunctivitis cases in patients treated with tralokinumab plus tcs were mild or moderate, with only one case leading to treatment discontinuation apreferred terms according to medical dictionary for regulatory activities, version 20.0. ● at 16 weeks, tralokinumab responders (defined as being iga-0/1 and/or easi-75 responders at week 16) were re-randomized 1:1 to continuation treatment with tralokinumab q2w or every 4 weeks (q4w) plus tcs for an additional 16 weeks. placebo responders continued with placebo and al non-responders received tralokinumab q2w plus tcs for an additional 16 weeks endpoints ● primary efficacy endpoints were an iga score of 0 (clear) or 1 (almost clear) [iga-0/1] and a 75% improvement in easi (easi-75), both at week 16 ● key secondary endpoints were change from baseline to week 16 in scoring ad (scorad) score, reduction of worst daily pruritus nrs (weekly average) 4, and dermatology life quality index (dlqi) score ● continuation endpoints included iga-0/1 at week 32 among patients with iga-0/1 at week 16 and easi-75 at week 32 among patients with easi-75 at week 16, both after initial randomization to tralokinumab concomitant tcs use during ecztra 3 ● tcs (mometasone furoate, 0.1% cream, 180−200 g. europe: class 3 [potent]; usa: class 4 [midstrength]) was supplied proactively from randomization to the end of treatment ● a thin film of the dispensed mometasone was applied by the patient once daily to active lesions as needed and discontinued when control was achieved ● lower-potency tcs or topical calcineurin inhibitor could be prescribed if needed on areas where the supplied tcs was not advisable or was considered unsafe safety ● adverse events assessments were performed at baseline and at each visit statistical analyses ● primary and key secondary endpoints for the initial 16-week treatment period were assessed using a hierarchical testing procedure and holm-bonferrioni multiplicity adjustment ● iga-0/1 and easi-75 at week 32 were summarized using descriptive statistics references 1. nutten s. ann nutr metab 2015;66(suppl 1):8–16. 2. weidinger s, novak n. lancet 2016;387:1109–1122. 3. eckert l et al. j am acad dermatol 2017; 77: 274–279.e273. 4. silverberg ji et al. ann allergy asthma immunol 2018;121:340–347. 5. dalgard fj et al. j invest dermatol 2015;135:984–991. 6. bieber t. allergy 2020;75:54–62. 7. tsoi lc et al. j invest dermatol 2019;139:1480–1489. 8. eichenfield lf et al. j am acad dermatol 2014;71:116–132. 9. boguniewicz m et al. j allergy clin immunol pract 2017;5:1519–1531. 10. popovic b et al. j mol biol 2017; 429: 208–219. disclosures the tralokinumab ecztra 3 study was sponsored by leo pharma. stephan weidinger has acted as an advisory board member/speaker/investigator for, and/or has received grants/research funding from, abbvie, almirall, laboratorie pharmaceutique, la roche-posay, leo pharma, lilly, novartis, pfizer, sanofi genzyme, and sanofi/regeneron. jonathan i. silverberg has acted as a consultant/advisory board member for, and/or has received grants/honoraria from, abbvie, anaptysbio, asana biosciences, galderma research and development, glaxosmithkline, glenmark, kiniksa, leo pharma, lilly, medimmune, menlo therapeutics, pfizer, puricore, regeneron, and sanofi. darryl toth has acted as an investigator/advisory board member for abbvie, arcutis, avillion, boehringer ingelheim, bristol-myers squibb, incyte, janssen, leo pharma, lilly, merck, pfizer, and regeneron. thomas bieber has acted as a lecturer and/or consultant for abbvie, almiral, anaptysbio, arena, asana biosciences, astellas, bioversys, boehringer ingelheim, celgene, daiichi sankyo, davos biosciences, dermavant/roivant, dermtreat, ds pharma, evaxion, flx bio, galapagos/morphosys, galderma, glaxosmithkline, glenmark, incyte, kymab, leo pharma, lilly, l´oréal, menlo therapeutics, novartis, pfizer, pierre fabre, sanofi/regeneron, ucb, and vectans. andrew f. alexis has acted as a consultant and/or received grants/research funding from almirall, beiersdorf, bristol-myers squibb, celgene, dermavant, foamix, galderma, leo pharma, l’oreal, menlo therapeutics, novartis, pfizer, sanofi/regeneron, scientis, ucb, unilever, and valeant (bausch health). boni e. elewski has acted as a consultant for, and/or received researching funding from, abbvie, anaptysbio, boehringer ingelheim, bristol-myers squibb, celgene, incyte, leo pharma, lilly, menlo therapeutics, merck, novartis, pfizer, regeneron, sun, valeant (ortho dermatologics), vanda, and verrica. andrew e. pink has acted as an advisor/speaker for abbvie, almirall, janssen, la roche-posay, leo pharma, lilly, novartis, pfizer, sanofi, and ucb. dirkjan hijnen has received honoraria as a consultant/advisory board member for, and/or received grants/honoraria from, abbvie, incyte, janssen, leo pharma, lilly, medimmune, pfizer, and sanofiregeneron. conclusions high levels of skin clearance were observed with bimekizumab after one dose and at week 16, compared with placebo. clinical responses were durable through 56 weeks, regardless of bimekizumab dosing schedule. bimekizumab was well-tolerated and the safety profile was consistent with previous studies.4–7 objectives to compare the efficacy and safety of bimekizumab with placebo over 16 weeks in patients with plaque psoriasis, and evaluate the effect of randomized treatment withdrawal, compared with continued treatment, in week 16 responders. background bimekizumab is a monoclonal igg1 antibody that has been rationally designed to selectively inhibit il-17f in addition to il-17a.1,2 both of these interleukins are implicated in the immunopathogenesis of plaque psoriasis (pso).3 bimekizumab led to substantial clinical improvements in patients with moderate to severe pso in the phase 2 be able study (nct02905006, nct03010527), with no unexpected safety findings.4,5 methods adult patients with moderate to severe pso were enrolled in the pivotal phase 3 be ready study (nct03410992), which incorporated a 16-week randomized, double-blinded, placebo-controlled period followed by a 40-week randomized withdrawal period (figure 1). • the co-primary endpoints were a 90% improvement from baseline in psoriasis area and severity index (pasi 90) and an investigator’s global assessment score of 0 or 1 (iga 0/1) at week 16. secondary endpoints included pasi 100 at week 16 and pasi 75 at week 4. other endpoints included pasi 75, pasi 90, and pasi 100 at other timepoints. • missing data were imputed with non-responder imputation (nri). • treatment emergent adverse events (teaes) were classified using meddra version 19.0. results patient population • baseline characteristics are shown in table 1. efficacy • co-primary endpoints of pasi 90 and iga 0/1 at week 16 were achieved by 90.8% and 92.6% of bimekizumab-treated patients, respectively, compared with 1.2% and 1.2% in the placebo group, respectively (p<0.001 for both). • response was rapid, with over 75% of bimekizumab-treated patients achieving pasi 75 at week 4, after just one dose (figure 2). • pasi 90 response was well-maintained in patients re-randomized to bimekizumab, regardless of dosing schedule (figure 3). • among patients re-randomized to placebo, loss of response was slow; median time to relapse (loss of pasi 75 response following re-randomization was ~28 weeks (~32 weeks from last bimekizumab dose). safety • overall, bimekizumab was well-tolerated; discontinuation due to teaes was low, and there were no deaths in the study (table 2). • all cases of oral candidiasis were localized, mild, or moderate superficial infections, and no cases led to discontinuation (table 2). the most common teaes with bimekizumab were nasopharyngitis, oral candidiasis, and upper respiratory tract infection. k. gordon,1 p. foley,2 j.g. krueger,3 a. pinter,4 k. reich,5 r. vender,6 v. vanvoorden,7 c. madden,8 l. peterson,8 a. blauvelt9 figure 1 study design author affiliations: 1medical college of wisconsin, milwaukee, wi, usa; 2skin health institute, carlton, victoria, australia; 3the rockefeller university, new york, ny, usa; 4university hospital frankfurt am main, department of dermatology, frankfurt am main, germany; 5center for translational research in inflammatory skin diseases, institute for health services research in dermatology and nursing, university medical center hamburg-eppendorf and skinflammation® center, hamburg, germany; 6division of dermatology, mcmaster university, hamilton, ontario, canada; 7ucb pharma, brussels, belgium; 8ucb pharma, raleigh, nc, usa; 9oregon medical research center, portland, or, usa. presented at fall clinical dermatology conference 2020 | october 29–november 1 | las vegas, nv efficacy and safety of bimekizumab in patients with moderate to severe plaque psoriasis: results from be ready, a 56-week phase 3, randomized, double-blinded, placebo-controlled study with randomized withdrawal references: 1durham l. curr rheumatol reports 2015;17:55; 2fujishima s. arch dermatol res 2010;302:499–505; 3johnston a. et al. j immunol 2013;190:2252–62; 4papp k. et al. jaad 2018;79(2):277–286, nct02905006; 5blauvelt a. et al. aad 2019 (op11180), nct03010527; 6glatt s. et al. br j clin pharm 2017;83(5):991i1001; 7glatt s. et al. ann rheum dis 2018;77:523–32. author contributions: substantial contributions to study conception/design, or acquisition/analysis/interpretation of data: kg, pf, jgk, ap, kr, rv, vv, cm, lp, ab; drafting of the publication, or revising it critically for important intellectual content: kg, pf, jgk, ap, kr, rv, vv, cm, lp, ab; final approval of the publication: kg, pf, jgk, ap, kr, rv, vv, cm, lp, ab. author disclosures: kg: honoraria and/or research support from abbvie, almirall, amgen, boehringer ingelheim, bristol-myers squibb, celgene, dermira inc., eli lilly, janssen, novartis, pfizer, sun pharma, and ucb pharma. pf: received grant support from abbvie, amgen, celgene, eli lilly, janssen, merck, novartis, pfizer, sun pharma, and sanofi; served as an investigator for abbvie, amgen, astrazeneca, bristol-myers squibb, boehringer ingelheim, botanix, celgene, celtaxsys, csl, cutanea, dermira inc., eli lilly, galderma, genentech, geneseq, gsk, hexima, janssen, leo pharma, merck, novartis, pfizer, regeneron pharmaceuticals inc., reistone, roche, sanofi, sun pharma, ucb pharma, and valeant; served on the advisory board of abbvie, amgen, bristol-myers squibb, celgene, eli lilly, galderma, janssen, leo pharma, mayne pharma, merck, novartis, pfizer, sanofi, sun pharma, ucb pharma, and valeant; served as a consultant for bristol-myers squibb, eli lilly, janssen, novartis, pfizer, ucb pharma, and wintermute; received travel grants from abbvie, eli lilly, janssen, leo pharma, merck, novartis, pfizer, roche, and sanofi; served as a speaker for or received honoraria from abbvie, celgene, eli lilly, galderma, janssen, leo pharma, merck, novartis, pfizer, and roche. jgk: grants paid to institution from abbvie, akros, allergan, amgen, avillion, biogen ma, boehringer ingelheim, botanix, bristol-myers squibb, celgene, eli lilly, exicure, incyte, innovaderm, janssen, leo pharma, novan, novartis, paraxel, pfizer, regeneron, sienna, ucb pharma, and vitae; personal fees from abbvie, allergan, almirall, amgen, arena, aristea, asana, aurigne, biogen, boehringer ingelheim, bristol-myers squibb, celgene, eli lilly, escalier, leo pharma, nimbus, novartis, menlo, sanofi, sienna, sun pharma, pfizer, ucb pharma, and valeant. ap: worked as an investigator and/or speaker and/or advisor for abbvie, almirall hermal, amgen, biogen, boehringer ingelheim, celgene, gsk, eli lilly, galderma, hexal, janssen, leo pharma, mc2, medac, merck serono, mitsubishi, msd, novartis, pfizer, tigercat pharma, regeneron, roche, sandoz biopharmaceuticals, schering-plough, and ucb pharma. kr: served as advisor and/or paid speaker for and/or participated in clinical trials sponsored by abbvie, affibody, almirall, amgen, avillion, biogen, boehringer ingelheim, bristol-myers squibb, celgene, centocor, covagen, dermira inc., eli lilly, forward pharma, fresenius medical care, galapagos, gsk, janssen-cilag, kyowa kirin, leo pharma, medac, merck sharp & dohme, miltenyi biotec, novartis, ocean pharma, pfizer, regeneron, samsung bioepis, sanofi, sun pharma, takeda, ucb pharma, valeant, and xenoport. rv: consultant, and/or scientific advisor, and/or investigator, and/or speaker for amgen, abbvie, astellas, bausch health/valeant, bristolmyers squibb, boehringer ingelheim, celgene, dermira inc., eli lilly, galderma, gsk, janssen, leo pharma, merck, sharp & dohme, merck serono, novartis, pfizer, regeneron, roche, sanofi-aventis/genzyme, sun pharma, takeda, and ucb pharma. vv, cm, lp: employees of ucb pharma. ab: served as a scientific adviser and/or clinical study investigator for abbvie, aclaris, allergan, almirall, athenex, boehringer ingelheim, bristol-myers squibb, dermavant, dermira inc., eli lilly, forte, galderma, janssen, leo pharma, novartis, ortho, pfizer, rapt, regeneron, sandoz, sanofi genzyme, sun pharma, and ucb pharma; paid speaker for abbvie. acknowledgements: this study was funded by ucb pharma. we thank the patients and their caregivers in addition to the investigators and their teams who contributed to this study. the authors acknowledge susanne wiegratz, msc, ucb pharma, monheim am rhein, germany and eva cullen, phd, ucb pharma, brussels, belgium for publication coordination and critical review, joe dixon, phd, costello medical, cambridge, uk, for medical writing and editorial assistance, and the costello medical design team for design support. all costs associated with development of this poster were funded by ucb pharma in accordance with the good publication practice (gpp3) guidelines. aone placebo-randomized patient achieved pasi 90 at week 16 and continued to receive placebo treatment to week 56. synopsis patients were randomized 4:1 to receive bimekizumab every four weeks or placebo for an initial 16 weeks of treatment methods to compare the efficacy and safety of bimekizumab with placebo in patients with moderate to severe plaque psoriasis objective be ready met both of its co-primary endpoints at week 16, with significantly higher pasi 90 and iga 0/1 responder rates vs placebo results pasi 90 high levels of skin clearance were observed with bimekizumab at week 16 bimekizumab was well-tolerated and the safety profile was consistent with previous studies conclusion iga 0/1 table 1 baseline characteristics figure 2 pasi 75, pasi 90, and pasi 100 over 16 weeks (itt, nri) figure 3 pasi 90 in maintenance and withdrawal arms (week 16 pasi 90 responders, nri) table 2 safety placebo n=86 bimekizumab 320 mg q4w n=349 all patients n=435 age (years), mean ± sd 43.5 ± 13.1 44.5 ± 12.9 44.3 ± 12.9 male, n (%) 58 (67.4) 255 (73.1) 313 (72.0) caucasian, n (%) 79 (91.9) 324 (92.8) 403 (92.6) weight (kg), mean ± sd 91.7 ± 22.2 88.7 ± 20.6 89.3 ± 20.9 duration of pso (years), mean ± sd 19.1 ± 12.8 19.6 ± 13.3 19.5 ± 13.2 pasi, mean ± sd 20.1 ± 7.6 20.4 ± 7.6 20.3 ± 7.6 bsa (%), mean ± sd 24.4 ± 16.0 24.6 ± 15.2 24.5 ± 15.4 iga, n (%) 3: moderate 62 (72.1) 242 (69.3) 304 (69.9) 4: severe 24 (27.9) 107 (30.7) 131 (30.1) dlqi total, mean ± sd 11.3 ± 6.9 10.4 ± 6.3 10.6 ± 6.4 any prior systemic therapy, n (%) 71 (82.6) 276 (79.1) 347 (79.8) prior biologic therapy, n (%) 37 (43.0) 154 (44.1) 191 (43.9) anti-tnf 12 (14.0) 62 (17.8) 74 (17.0) anti-il-17 18 (20.9) 85 (24.4) 103 (23.7) anti-il-23 5 (5.8) 28 (8.0) 33 (7.6) anti-il-12/23 11 (12.8) 40 (11.5) 51 (11.7) bsa: body surface area; dlqi: dermatology life quality index; iga: investigator’s global assessment; il: interleukin; itt: intent-to-treat; lft: liver function test; mace: major adverse cardiovascular event; nec: not elsewhere classified; nri: non-responder imputation; pasi 75/90/100: ≥75/90/100% improvement from baseline in psoriasis area and severity index; pso: psoriasis; q4w: every 4 weeks; q8w: every 8 weeks; sd: standard deviation; sib: suicidal-ideation behavior ; teae: treatment emergent adverse event; tnf: tumor necrosis factor. initial period (weeks 0–16) randomized withdrawal period (weeks 16–56) bimekizumab 320 mg q4w placebo (n=86) n (%) bimekizumab 320 mg q4w (n=349) n (%) placebo (n=105) n (%) bimekizumab 320 mg q8w (n=100) n (%) bimekizumab 320 mg q4w (n=106) n (%) incidence of teaes any teae 35 (40.7) 213 (61.0) 72 (68.6) 77 (77.0) 78 (73.6) serious teaes 2 (2.3) 6 (1.7) 4 (3.8) 3 (3.0) 5 (4.7) discontinuation due to teaes 1 (1.2) 4 (1.1) 3 (2.9) 2 (2.0) 0 drug-related teaes 7 (8.1) 65 (18.6) 23 (21.9) 23 (23.0) 28 (26.4) severe teaes 1 (1.2) 3 (0.9) 4 (3.8) 1 (1.0) 4 (3.8) deaths 0 0 0 0 0 common teaes (>5% of patients) nasopharyngitis 4 (4.7) 23 (6.6) 20 (19.0) 23 (23.0) 11 (10.4) oral candidiasis 0 21 (6.0) 6 (5.7) 9 (9.0) 12 (11.3) upper respiratory tract infection 7 (8.1) 14 (4.0) 5 (4.8) 8 (8.0) 12 (11.3) teaes of interest inflammatory bowel disease 0 0 0 0 0 adjudicated sib 0 0 0 0 0 malignancies 0 1 (0.3)a 1 (1.0)b 0 0 neutropenia 0 3 (0.9) 0 1 (1.0) 0 hypersensitivity reactionsc 1 (1.2) 12 (3.4) 3 (2.9) 2 (2.0) 3 (2.8) adjudicated mace 0 0 0 1 (1.0)d 0 hepatic events 1 (1.2) 10 (2.9) 0 3 (3.0) 8 (7.5) liver function analysese 1 (1.2) 9 (2.6) 0 2 (2.0) 8 (7.5) fungal infectionsf,g 2 (2.3) 40 (11.5) 7 (6.7) 14 (14.0) 22 (20.8) candida infections 0 27 (7.7) 6 (5.7) 10 (10.0) 16 (15.1) tinea infections 0 9 (2.6) 0 1 (1.0) 4 (3.8) aone case of basal cell carcinoma; bone case of prostate cancer; chypersensitivity reactions were predominantly cutaneous, with no cases of acute anaphylaxis in any treatment group; da non-fatal myocardial infarction in a 53-year old male with 6 pre-existing cardiovascular risk factors, which was not attributed to the study drug; ein the initial treatment period, incidence of lft elevations with bimekizumab was generally low and comparable to placebo; majority of lft elevations were transient and resolved by end of study; fall fungal infections not classified as candida or tinea were classified as fungal infections nec; gin addition, all opportunistic infections were localized mucocutaneous fungal infections defined as opportunistic by convention; there were no systemic opportunistic infections or cases of active tuberculosis reported. *p<0.001 versus placebo. for pasi 75 at week 4, and pasi 90/pasi 100 at week 16, p values for the comparison of treatment groups were based on the cochran–mantel–haenszel test from the general association; for other comparisons, p values for a general association were based on a stratified cochran–mantel–haenszel test, where region and prior biologic exposure were used as stratification variables, are considered nominal, and were not controlled for multiplicity. placebo responder rates at week 4: pasi 75=1.2%, pasi 90=0%, pasi 100=0%; placebo responder rates at week 16: pasi 75=2.3%, pasi 90=1.2%, pasi 100=1.2%. *nominal p<0.001 versus placebo. p values for the comparison of treatment groups were based on stratified cochran–mantel–haenszel test, where region and prior biologic exposure were used as stratification variables. patients randomized to bimekizumab 320 mg q4w who achieved pasi 90 at week 16 were re-randomized for maintenance treatment; for patients re-randomized to placebo, the last dose of bimekizumab was at week 12. n=349 n=86 n=100 n=106 n=105 week 16baseline week 56 20 weeks after last dose for patients not enrolling in extension study: safety follow-up 2–5 weeks bimekizumab 320 mg q4w bimekizumab 320 mg q4w 12-week escape arm: bimekizumab 320 mg q4w bimekizumab 320 mg q8w placeboa placeboa <pasi 75 from week 20 <pasi 90 open-label extension study (be bright) 4:1 randomization ≥pasi 90 1:1:1 re-randomization co-primary endpoints pasi 90 and iga 0/1 at week 16 screening initial treatment period randomized withdrawal period 75.9%* 45.3%* 18.9%* pasi 75 pasi 90 pasi 100 95.4%* 90.8%* 68.2%* p ro p o rt io n o f p a ti e n ts ( % ) 0 1 2 4 8 weeks 12 16 0 25 50 75 100 placebo (n=86) bimekizumab 320 mg q4w (n=349)dose p ro p o rt io n o f p a ti e n ts ( % ) 0 16 20 24 28 32 36 40 44 48 52 56 weeks 0 25 50 75 100 placebo (n=105) bimekizumab 320 mg q4w (n=106) bimekizumab 320 mg q8w (n=100) 16.2% 86.8%* 91.0%* proportion of patients achieving pasi 90 (%) at week 16 90.8% bimekizumab 320 mg q4w (n=349) placebo (n=86) p<0.001 1.2% bimekizumab 320 mg q4w (n=349) placebo (n=86) 1.2% proportion of patients achieving iga 0/1 (%) at week 16 92.6% p<0.001 previously presented at aad 2020 integrated safety and efficacy analysis of fmx103 1.5% topical minocycline foam for the treatment of moderate-to-severe papulopustular rosacea: results from two phase 3 studies james q. del rosso, do1; linda stein gold, md2; leon kircik, md3; neal d. bhatia, md4; neil sadick, md5; matthew zirwas, md6; edward lain, md7; iain stuart, phd8 1jdr dermatology research/thomas dermatology, las vegas, nv; 2 henry ford health system, detroit, mi; 3icahn school of medicine at mount sinai, new york, ny; 4therapeutics clinical research, san diego, ca; 5sadick dermatology, new york, ny; 6dermatologists of the central states, columbus, oh; 7sanova dermatology, austin, tx; 8menlo therapeutics inc., bridgewater, nj introduction • rosacea is a common, chronic, inflammatory cutaneous disorder involving the face that affects approximately 16 million individuals in the united states1,2 • rosacea is typically characterized by cutaneous signs such as flushing, erythema, edema, papules, and pustules1-5 • topical therapies such as metronidazole, azelaic acid, and ivermectin are considered first-line therapies for papulopustular rosacea2-5 – oral tetracyclines, specifically doxycycline and minocycline, are mainstays of treatment for moderate-tosevere disease; however, they have the potential for significant systemic side effects2,4 – independent of their antimicrobial activity, tetracyclines may exert beneficial effects in rosacea due, in part, to their anti-inflammatory, antiapoptotic, and antiangiogenic activities6 • fmx103 1.5% is a topical minocycline foam being developed for the treatment of moderate-to-severe papulopustular rosacea7,8 – the efficacy, safety, and tolerability of fmx103 1.5% from two identical, phase 3, randomized, double-blind, vehicle-controlled studies, fx2016-11 (study 11) and fx2016-12 (study 12), have previously been presented8 • objective: to compare integrated efficacy and safety of fmx103 1.5% vs vehicle administered daily for 12 weeks methods • the 2 pivotal phase 3 studies (fx2016-11, study 11; fx2016-12, study 12) were randomized, double-blind comparisons of fmx103 1.5% with vehicle foam (figure 1) • qualified subjects were enrolled and randomly assigned in a 2:1 ratio to receive either fmx103 1.5% or vehicle • subjects applied the assigned study drug once daily for 12 weeks and returned for visits at weeks 2, 4, 8, and 12 • the efficacy data from studies 11 and 12 were pooled for analysis both in totality and for the predefined subgroup of baseline disease severity (moderate, iga=3; severe, iga=4) • safety endpoints included adverse events and local facial tolerability assessments, which were summarized for the overall pooled population, as well as for predefined subgroups including sex, race, age, and baseline disease severity figure 1. study design week 12baseline key inclusion criteria • males and nonpregnant females ≥18 years • moderate-to-severe facial papulopustular rosacea (iga score of 3 or 4) • >15 to ≤75 facial papules and pustules, excluding lesions involving eyes and scalp; ≤2 nodules on the face • presence or history of facial erythema or flushing integrated efficacy populationa (n=1522) vehicle foam (n=513) fmx103 1.5% (n=1009) study 11, n=256 study 12, n=257 study 11, n=495 study 12, n=514 • • co-primary efficacy endpoints absolute change in the inflammatory lesion count at week 12 compared to baseline iga success rate (dichotomized as yes/no) at week 12, where success was defined as an iga score of 0 or 1, and at least a 2-grade improvement (decrease) from baseline week 4 week 8 athe integrated efficacy population consisted of all randomized subjects that were pooled from studies 11 (n=751) and 12 (n=771). one subject was randomized but discontinued prior to taking the first dose and was therefore not included in the integrated safety population. iga, investigator’s global assessment; based upon a 5-point scale with 0=clear, 1=almost clear, 2=mild, 3=moderate, and 4=severe. results baseline demographics and disease characteristics • 1522 subjects were included in the integrated efficacy population • baseline demographics and disease characteristics are shown in table 1 • the majority of subjects were female (70.6%) and white (96.4%). the mean age was 50.0 and ranged from 18-86 years. at baseline, 86.9% and 13.1% of subjects had moderate (iga=3) or severe (iga=4) disease, respectively • baseline demographics and disease characteristics were similar across treatment groups table 1. baseline demographics and disease characteristics variable fmx103 1.5%(n=1009) vehicle foam (n=513) overall (n=1522) mean age (sd) 49.9 (13.84) 50.3 (13.17) 50 (13.61) 18 to 40 years, n (%) 265 (26.3) 118 (23.0) 383 (25.2) 41 to 64 years, n (%) 588 (58.3) 311 (60.6) 899 (59.1) 65 years, n (%) 156 (15.5) 84 (16.4) 240 (15.8) sex, m (%) male 289 (28.6) 159 (31.0) 448 (29.4) female 720 (71.4) 354 (69.0) 1074 (70.6) race white 973 (96.5) 491 (96.1) 1464 (96.4) black 14 (1.4) 5 (1.0) 19 (1.3) other 21 (2.1) 15 (2.9) 36 (2.4) mean inflammatory lesion count, n (sd) 29.2 (12.48) 29.6 (12.57) 29.4 (12.5) iga score, n (%) 3 – moderate 887 (87.9) 435 (84.8) 1322 (86.9) 4 – severe 122 (12.1) 78 (15.2) 200 (13.1) iga, investigator’s global assessment; sd, standard deviation. note that percentages exclude missing values. pooled efficacy data • in the combined analysis of the two pivotal phase 3 studies, fmx103 1.5% demonstrated statistically significant benefit compared to vehicle foam for both co-primary endpoints (figure 2) – at week 12, fmx103 1.5% demonstrated a significantly greater reduction from baseline in inflammatory lesions than vehicle foam (figure 2a) – a significantly greater number of subjects receiving fmx103 1.5% achieved iga treatment success at week 12 than those receiving vehicle foam (figure 2b) figure 2. co-primary efficacy endpoints % ig a s uc ce ss a t w ee k 12 r ed uc tio n fr om b as el in e at w ee k 12 in in fla m m at or y le si on s (l s m ea n) ba -20 -16 -12 -8 -4 -18 -14 -10 -6 0 -2 -18.0 n=1009 fmx103 1.5% -14.9 n=513 vehicle foam p<0.001, lsm diff: 3.0 lsm diff 95% ci: 1.92, 4.16 0 20 40 60 10 30 50 fmx103 1.5% n=1009 50.6% vehicle foam n=513 41.0% p<0.001 rr: 1.24; 95% ci: 1.095, 1.394 iga, investigator’s global assessment; lsm diff, lsmean difference; ci, confidence interval; rr, risk ratio. integrated efficacy population (multiple imputation). • fmx103 1.5% demonstrated a statistically significant advantage over vehicle foam for inflammatory lesions beginning as early as week 4 (figure 3) – the fmx103 1.5% group exhibited a significantly greater reduction in inflammatory lesions at week 4 than the vehicle foam group – this statistically significant advantage over vehicle was maintained at weeks 8 and 12 figure 3. change from baseline in inflammatory lesion counts by visit r ed u ct io n f ro m b as el in e at w ee k 12 in in fl am m at o ry le si o n s (l s m d if f) -25 -20 -15 -10 -5 0 0 4 8 12 fmx103 1.5% n=1009 vehicle foam, n=513 week integrated efficacy population (multiple imputation); lsm diff, least squares mean difference • fmx103 1.5% demonstrated a statistically significant advantage over vehicle foam for iga treatment success beginning as early as week 4 (figure 4) – this statistical advantage over vehicle was maintained throughout the study, with approximately half of the subjects in the fmx103 1.5% group achieving treatment success by week 12 figure 4. iga treatment success over time % ig a tr ea tm en t s uc ce ss 0 50 25 75 week 4 128 fmx103 1.5% (n=1009) vehicle foam (n=513) 16.0 9.4 37.8 30.0 50.6 41.0 p=0.001 p=0.003 p<0.001 iga, investigator’s global assessment; integrated efficacy population (multiple imputation); p values are based on common risk ratios. efficacy results in the patient subgroups scored as moderate or severe at baseline • fmx103 1.5% demonstrated statistically significant advantages over vehicle foam in both baseline disease severity subgroups (figure 5) – in both moderate (iga=3) and severe (iga=4) subpopulations, the change from baseline at week 12 in inflammatory lesions was significantly greater in the fmx103 1.5% group than in the vehicle foam group (figure 5a) – similarly, a significantly greater number of subjects in the fmx103 1.5% group achieved iga treatment success by week 12 than in the vehicle foam group, regardless of baseline disease severity (figure 5b) – the treatment effect for fmx103 1.5% vs vehicle foam was more pronounced in the severe subgroup than in the moderate subgroup for both inflammatory lesions (figure 5a) and iga treatment success (figure 5b) figure 5. efficacy of fmx103 1.5% across baseline disease severities r ed uc tio n fr om b as el in e at w ee k 12 in in fla m m at or y le si on s (l s m ea n) a -30 -20 -10 -25 -15 0 -5 -18.0 1009 overall baseline lesion counta: 513 -14.9 -16.7 887 moderate (iga=3) 435 -14.6 -26.0 122 severe (iga=4) 78 27.1 27.2 44.9 43.3 -15.1 p<0.001 p<0.001 p<0.001 % ig a tr ea tm en t s uc ce ss a t w ee k 12 b 0 20 40 10 30 60 50 50.6% 1009 overall 513 41.0% 52.5% 887 moderate (iga=3) 435 45.7% 36.8% 122 severe (iga=4) 78 14.9% p<0.001 p=0.01 p=0.003 n= n= fmx103 1.5% vehicle foam iga, investigator’s global assessment; integrated efficacy population (multiple imputation); abaseline lesion counts are based on observed cases. safety endpoints • overall summary of adverse events is shown in table 2 • all serious teaes were considered by the investigators as not related to study drug • 9 subjects reported 10 teaes resulting in study discontinuation – 7 subjects in the fmx103 1.5% group and 2 subjects in the vehicle group – one teae (moderate pruritis) leading to drug withdrawal was considered related to study drug. the subject was randomized to fmx103 1.5% treatment table 2. summary of teaes and aes in the integrated safety population fmx103 1.5% (n=1008) vehicle foam (n=513) overall (n=1521) subjects with any ae, n(%) 232 (23) 129 (25.1) 361 (23.7) number of aes 380 200 580 subjects with any teae, n(%) 219 (21.7) 122 (23.8) 341 (22.4) number of teaes 350 184 534 subjects with any serious teae, n(%) 3 (0.3) 5 (1.0) 8 (0.5) number of serious teaes 8a 9b 17 subjects with any treatment-related teae, n(%) 3 (0.3) 5 (1.0) 8 (0.5) number of treatment-related teaes 24c 17d 41 subjects with any teae leading to discontinuation, n(%) 7 (0.7) 2 (0.4) 9 (0.6) number of teaes leading to study discontinuation 8e 2f 10 anausea, chest discomfort, fatigue, seasonal allergy, dehydration, syncope, dyspnea, hypertension bgastrointestinal hemorrhage, chest pain, pyrexia, dyspnea, asthma, hypertension, myocardial infarction, tachycardia cpruritis, rash, dermatitis, dermatitis contact, hair color changes, nail discoloration, skin hyperpigmentation, application site pain, application site erythema, facial pain, nodule, migraine, dizziness, dysgeusia, aphthous ulcer, cheilitis, eye irritation, ophthalmic herpes simplex, sunburn dnail discoloration, rosacea, skin exfoliation, application site pain, facial pain, application site pruritis, headache, cellulitis, skin cancer, urine odor abnormal epruritis, dermal cyst, dermatitis, telangiectasia, influenza, urinary tract infection, bladder mass frash pustular, myocardial infarction • the incidence rate of the most frequently reported teaes (≥1% in any group) was similar between treatment groups (table 3) • overall, most subjects reported teaes that were not related to study drug (89.7%, 306/341) table 3. summary of non-cutaneous teaes in the integrated safety population by preferred term (≥1% in any group) teaes in ≥1% of subjects in either group, n (%) fmx103 1.5%(n=1008) vehicle foam (n=513) overall (n=1521) viral upper respiratory tract infection 24 (2.4) 12 (2.3) 36 (2.4) upper respiratory tract infection 19 (1.9) 13 (2.5) 32 (2.1) headache 14 (1.4) 10 (1.9)a 24 (1.6) sinusitis 11 (1.1) 2 (0.4) 13 (0.9) diarrhea 10 (1.0) 2 (0.4) 12 (0.8) a2 cases were considered to be treatment-related • the incidence rate of teaes by severity was similar between treatment groups (table 4) • overall, most subjects reported teaes that were mild (68.0%, 232/341) or moderate (29.9%, 102/341) in severity • 7 subjects (2.1%, 7/341) reported severe teaes • all severe teaes were considered not related to the study medication by the investigator table 4. summary of teaes by severity fmx103 1.5% (n=1008) vehicle foam (n=513) overall (n=1521) oa mild mod sevr oa mild mod sevr oa mild mod sevr subjects reporting any teae, n (%)a 219 (21.7) 145 (14.4) 71 (7.0) 3b (0.3) 122 (23.8) 87 (17.0) 31 (6.0) 4c (0.8) 341 (22.4) 232 (15.3) 102 (6.7) 7 (0.5) mod, moderate; oa, overall; sevr, severe. asubjects experiencing one or more adverse events are counted only once for each adverse event term and counted only by the maximum severity. if severity is missing, it is counted as severe. brosacea, post-traumatic headache, application site pain. cfall, dyspnea, asthma, pyrexia, myocardial infarction. • similar incidence rates of teaes were observed across both treatment groups for predefined subgroups (figure 6): – sex – race – age – baseline disease severity (iga) figure 6. summary of overall percentages of aes in all groups 0 15 45 50 a dv er se e ve nt s, % sex fmx103 1.5% vehicle foam 5 10 20 25 30 35 40 race age baseline iga severity female male white non-white 18-40 years 41-64 years ≥65 years iga 3 iga 4 22.9 25.7 18.7 19.5 21.5 23.4 27.8 31.8 18.5 26.3 22.3 22.2 25.2 26.2 23.0 21.821.6 24.1 • the majority of subjects in both treatment groups recorded local tolerability assessments as none or mild at both baseline and week 12 (figure 7) – similar rates of mild, moderate, and severe assessments were observed across both treatments and timepoints within each subgroup category – no notable differences were observed in facial tolerability assessments by subgroup – at week 12, all facial local tolerability assessments showed improvement compared to baseline – notable improvements in erythema were observed, with the percentage of patients with clear or almost clear signs of erythema increasing from 6.1% at baseline to 44.8% at week 12 figure 7. facial local tolerability assessments at baseline and week 12 in fmx103 1.5% treatment group bl wk 52 erythema bl wk 12 bl wk 12 bl wk 12 bl wk 12 bl wk 12 bl wk 12 bl wk 12 hyperpigmentation peeling/ desquamation itchingdryness/ xerosis flushing/ blushing burning/ stinging telangiectasia 10.55.1 34.3 28.9 36.2 63.8 18.3 0.7 clear severe moderate mild almost clear none mild moderate severe 1.3 1.0 12.5 20.2 52.3 83.9 17.1 50.5 37.4 72.0 44.2 76.7 57.2 81.9 64.9 74.754.8 61.0 27.6 13.3 38.7 39.0 36.8 23.9 35.0 20.0 31.5 16.1 28.3 22.532.6 18.8 19.8 2.8 40.3 9.6 25.2 4.0 20.1 3.3 11.0 1.9 6.8 2.8 0.1 0.0 0.3 0.0 4.0 0.9 0.6 0.1 0.6 0.0 0.2 0.1 0.0 0.0 0% 25% 50% 100% 75% s ub je ct s w ith lo ca l s ig ns o r sy m pt om s, % bl=baseline, n=1008; wk 12=week 12, n=897; all symptoms were evaluated on a 4-point scale consisting of 0=none, 1=mild, 2=moderate, and 3=severe, except for erythema, which was evaluated on a 5-point scale consisting of 0=clear, 1=almost clear, 2=mild, 3=moderate, and 4=severe. summary efficacy summary • fmx103 1.5% demonstrated efficacy over vehicle foam in treating papulopustular rosacea in a pooled population of ~1500 subjects, with effects being observed as early as 4 weeks into treatment • sub-analyses were performed on the integrated data set to characterize the efficacy of fmx103 1.5% in treating papulopustular rosacea in predefined subgroups of subjects – fmx103 1.5% demonstrated significant efficacy benefits in treating papulopustular rosacea in subgroups of subjects that had either moderate (iga=3) or severe (iga=4) disease severity at baseline, with a more pronounced effect in the severe subpopulation • findings from this integrated efficacy analysis are thus consistent with those from the individual phase 3 studies, both of which achieved statistically significant differences for all primary efficacy endpoints and further demonstrated significant differences as early as 4 weeks into treatment safety summary • fmx103 1.5% was generally safe and well tolerated • 341 (22.4%) subjects reported a teae during the 2 identical double-blind phase 3 studies – in general, no differences were observed between treatment groups in the incidence of teaes – the most frequently reported teaes for fmx103 1.5% vs vehicle, respectively, were viral upper respiratory tract infection (2.4% vs 2.3%), upper respiratory tract infection (1.9% vs 2.5%), and headache (1.4% vs 1.9%) – the majority of teaes reported were mild in severity (overall 68%) – 7 subjects reported severe teaes; all were considered to be unrelated to treatment, and were similar between treatment groups • teaes were similar across clinically relevant subgroups, including sex, race, age, and baseline iga score • at week 12, all facial tolerability assessments had higher percentages of “none” compared to baseline and trended towards improving scores in the fmx103 1.5% treatment group limitations • a limitation of these studies relates to the generalizability of the data to a more ethnically diverse population, or to patients not conforming to the inclusion criteria of the studies • an inclusionary criterion was to avoid common rosacea triggers, so efficacy would not be affected by such triggers conclusions • fmx103 1.5% demonstrated statistically significant differences compared with vehicle for both co-primary endpoints in a pooled population of two phase 3 studies, and numerical advantages across clinically relevant subpopulations • the results of the pooled safety analysis of 1,521 patients from two identical phase 3 studies demonstrated that fmx103 1.5% topical minocycline foam appeared to be safe and well tolerated with no serious treatmentrelated adverse events when administered daily for 12 weeks for the treatment of moderate-to-severe facial papulopustular rosacea disclosures/acknowledgment disclosures dr. del rosso is a consultant for aclaris, almirall, athenex, cutanea, dermira, ferndale, galderma, genentech, leo pharma, menlo, novan, ortho, pfizer, promius, sanofi/regeneron, skinfix, and sunpharma; he has received research support from aclaris, almirall, athenex, botanix, celgene, cutanea, dermira, galderma, genentech, leo pharma, menlo, novan, ortho, promius, regeneron, sunpharma, and thync; he receives honoraria from aclaris, celgene, galderma, genentech, leo pharma, novartis, ortho, pfizer, promius, sanofi/regeneron, and sunpharma; and he participates in speakers bureaus for honoraria from aclaris, celgene, galderma, genentech, leo pharma, novartis, ortho, pfizer, promius, sanofi/regeneron, and sunpharma. dr. stein gold is an advisor and investigator for foamix pharmaceuticals inc, galderma, leo pharma, novartis, and valeant and is an investigator for janssen, abbvie, and solgel. dr. kircik is an investigator and consultant for foamix pharmaceuticals. dr. bhatia is an investigator and consultant for foamix pharmaceuticals. dr. sadick is a consultant for almirall, galderma usa, venus concept, allergan, inc., auxilium pharmaceuticals, inc., btg plc, cynosure, inc., endo international plc, eternogen, ferndale loboratories, inc., gerson lehrman group, merz aesthetics, valeant pharmaceticals international; an advisor for slender medical ltd., galderma laboratories, l.p., merz aesthetics, suneva medical, inc., a stockholder in vascular insights, llc; a principal investigator for actavis, anacor pharmaceuticals, inc., bayer, biorasi, llc, cassiopea spa, celgene corporation, cynosure, inc., dusa pharmaceuticals, inc., eli lilly and company, endo international plc, galderma usa, hydropeptide, llc, neostrata, novartis, nutraceutical wellness, llc., palomar medical technologies, roche laboratories, samumed, llc, valeant pharmaceuticals international, vanda pharmaceuticals; a speaker for celgene corporation, cutera, inc., endymed medical inc. usa, solta medical, storz medical ag, and venus concept. dr. zirwas is a consultant for regeneron/sanofi, fit bit, l’oreal, menlo, leo, lilly, ortho derm, arcutis; an investigator for regeneron/sanofi, leo, janssen, incyte, foamix, ucb, pfizer, lilly, asana, avillion, abbvie, edessa biotech, galderma, dermavant, arcutis; a speaker for regeneron/sanofi, genench/novartis and part owner of asepticmd. dr. lain is an advisor, speaker, and investigator for foamix pharmaceuticals. dr. stuart is an employee and stockholder at menlo therapeutics inc. acknowledgment editorial support was provided by scient healthcare communications. funding this study is funded by foamix pharmaceuticals ltd, a wholly owned subsidiary of menlo therapeutics inc. references 1. li wq, cho e, khalili h, et al. rosacea, use of tetracycline, and risk of incident of inflammatory bowel disease in women. clin gastroenterol hepatol. 2016;14(2):220-225. 2. taieb a, gold ls, feldman sr, et al. cost-effectiveness of ivermectin 1% cream in adults with papulopustular rosacea in the united states. j manag care spec pharm. 2016;22(6):654-665. 3. rainer bm, kang s, chien al. rosacea: epidemiology, pathogenesis, and treatment. dermatoendocrinol. 2017;9(1):e1361574. 4. oge lk, muncie hl, phillips-savoy ar. rosacea: diagnosis and treatment. am acad fam physicians. 2015;92(3):187-196. 5. schaller m, schofer h, homey b, et al. rosacea management: update on general measures and topical treatment options. j dtsch dermatol ges. 2016;14(s6):17-27. 6. sapadin an , fleischmajer r. tetracyclines: nonantibiotic properties and their clinical implications. j am acad dermatol 2006;54:258-65. 7. mrowietz u, kedem th, keynan r, et al. a phase ii, randomized, double-blind clinical study evaluating the safety, tolerability, and efficacy of a topical minocycline foam, fmx103, for the treatment of facial papulopustular rosacea. am j clin dermatol. 2018;19(3)427-436. 8. stein gold l, del rosso jq, kircik l, et al. minocycline 1.5% foam for the topical treatment of moderateto-severe papulopustular rosacea: results of two phase 3, randomized, clinical trials. j am acad dermatol. 2020; doi: 10.1016/j.jaad.2020.01.043 presented at fall clinical dermatology conference® 2017 | las vegas, nv, usa | 12–15 october, 2017 | previously presented at eadv 2017 – sensitivity: >10 times more sensitive than the previous assay used in other czp pk studies (lower limit of quantification [lloq]: 0.032 µg/ml).8 – specificity: requires binding of czp to tnf and detection with an anti-peg antibody.8 • the presence of anti-czp antibodies in blood was determined using a previously validated enzyme-linked immunosorbent assay (elisa). samples were defined as positive if anti-czp antibody levels were >2.4 units/ml.9 study assessments • blood samples were collected from the mothers, umbilical cords, and infants at delivery, and from infants again at weeks 4 and 8 post-delivery (figure 1). • safety analyses included all mothers who received at least one dose of czp, and the infants of participating mothers. adverse events (aes) were coded according to the meddra v18.1. statistical analyses • no formal sample size calculations were performed, as no statistical hypotheses were tested. all pk variables were based on the observed values; no imputation for missing data was used. results baseline characteristics • 21 czp-treated pregnant women were screened; 5 women discontinued screening. based on preliminary pk and safety analyses, which showed consistent data for the initial mother/infant pairs enrolled, the study concluded with a final enrollment of 16 pregnant women, which was deemed sufficient to assess the primary objective. • of the 16 mothers who entered the sampling period, 15 were on czp 200 mg q2w and 1 on 400 mg q4w (table 1). • the gestational age and weight at birth of the 16 infants were within the expected range for healthy infants (table 1). background • women affected by chronic inflammatory diseases, such as psoriatic disease, need effective and safe treatments during pregnancy.1,2 • adequate disease control is important to reduce the risk of adverse pregnancy outcomes.3 • anti-tnfs are efficacious, but because most cross the placenta, treatment is often stopped during pregnancy.4,5 • certolizumab pegol (czp), due to its fc-free molecular structure, is not expected to undergo active placental transfer compared to other antibody-based anti-tnfs.6,7 • crib (nct02019602) is the first prospective, industry-sponsored study designed to evaluate placental transfer of czp from the mother to her infant. methods patients and study design • crib was a pharmacokinetic (pk) study of pregnant women receiving commercial czp for an approved indication. • the primary endpoint was the concentration of czp in the infants’ plasma at birth (figure 1). • key inclusion criteria: – patients were ≥30 weeks pregnant with a singleton or twins at the time of informed consent. – patients were being treated with czp as per the locally approved label and prescriber’s discretion. – patients started or decided to continue czp treatment independently from and prior to participating in this study and in accordance with the treating physician. – patients received a czp dose within 35 days prior to delivery. • key exclusion criteria: – patients had any pregnancy-related, clinically significant abnormality noted on obstetric ultrasound or other imaging assessment, or had significant laboratory abnormalities during their pregnancy. – patients were taking or had taken any medication with strong positive evidence of human fetal risk of teratogenicity during pregnancy. – patients had received treatment with any biological therapeutic agent, including anti-tnfs other than czp, during pregnancy. detection of czp and anti-czp antibodies • czp concentrations in blood were measured using a highly sensitive, czp-specific electrochemiluminescence immunoassay (figure 2): references 1. chakravarty e. et al. bmj open 2014;4:e004081; 2. de man y. et al. arthritis rheum 2009;60(11):3196–3206; 3. mouyis m. et al. j rheumatol 2017;44:128–129; 4. ng s. et al. expert rev clin immunol 2013;9(2):161–173; 5. østensen m. et al. curr opin pharmacol 2013;13(3):470–475; 6. mahadevan u. et al. clin gastroenterol hepatol 2013;11(3):286–292; 7. förger f. et al. joint bone spine 2016;83:341–343; 8. smeraglia j et al. bioanalysis 2017;9(16):1217–1226; 9. wade j. et al. j clin pharmacol 2015;55(8):866–874; 10. clowse m. et al. arthritis rheumatol 2017;69(suppl 10):abstract 1309. author contributions substantial contributions to study conception/design, or acquisition/analysis/interpretation of data: abk, xm, ba, af, ff, am, r-mf, avt, ls, js, mt, eh, mw, ec; drafting of the publication, or revising it critically for important intellectual content: abk, xm, ba, af, ff, am, r-mf, avt, ls, js, mt, eh, mw, ec; final approval of the publication: abk, xm, ba, af, ff, am, r-mf, avt, ls, js, mt, eh, mw, ec. disclosures abk: consultant for: ucb pharma, dermira, janssen, abbvie; xm: grant/research support: biogen, pfizer, ucb pharma; consultant for: bms, gsk, lfb, pfizer, ucb pharma. ba: grant/research support: janssen, ucb pharma; speaker’s fees: abbvie, american reagent, janssen, ucb pharma. af: grant/research support: ucb pharma. ff: grant/research support: ucb pharma; speaker’s fees: mepha, roche, ucb pharma. am: grant/research support: msd, abbvie, pfizer, ucb pharma; consultant for: msd, abbvie, pfizer, ucb pharma. r-mf: consultant for: ucb pharma. avt: grant/ research support: pfizer, abbvie, ucb pharma, janssen-cilag, celgene, novartis, msd; speaker’s fees: msd, janssen-cilag, pfizer; consultant for: abbvie, novartis, janssen-cilag, pfizer. ls, js, mt, eh, mw: employee of ucb pharma. ec: grant/research support: ucb pharma. acknowledgements this study was funded by ucb pharma. we are indebted to the mothers and their infants for their altruistic participation. we thank the nurses, investigator teams, and nicole hurst (ppd), and acknowledge cécile ecoffet and simone e. auteri (ucb pharma) for publication coordination. editorial services for this poster were provided by costello medical consulting. all costs associated with the development of this poster were funded by ucb pharma. n (%)a mothers (n=21)b infants (n=16) any teaes 15 (71.4) 5 (31.3) severe teaes 2 (9.5) 1 (6.3) discontinuation due to teaes 2 (9.5) 0 drug-related teaes 3 (14.3) 1 (6.3) serious teaesc 7 (33.3) 2 (12.5) deaths 0 0 serious teaes by mother-infant pair sf placental insufficiency premature baby n/a 1 arrested labor none 2 arrested labor none 3 prolonged labor none 4 gestational diabetes polyhydramnios none 5 none hypoglycemia infection 6 perineal abscess none 7 vaginal laceration macrosomia meconium in amniotic fluid teaes were defined as any ae captured from the time of informed consent until the safety followup; bold text indicates severe teaes. anumber of mothers or infants reporting at least one ae for the indicated category; bsafety set for mothers (includes 5 screen failures); cserious teaes were classified using the fda definition of serious aes. teae: treatment-emergent adverse event; sf: screen failure; n/a: not applicable. table 2. safety overview figure 2. czp-specific immunoassay athe sulfo-tag label emits light upon electrochemical stimulation initiated at the electrode surface. peg: polyethylene glycol; fab’: fragment antigen-binding; tnf: tumor necrosis factor. median (min, max), unless stated otherwise mothers (n=16)a age, years 31 (18, 40) mother’s indication for czp treatment, n rheumatoid arthritis 11 crohn’s disease 3 psoriatic arthritis 1 axial spondyloarthritis/ankylosing spondylitis 1 delivery type, n vaginal 14 cesarean section 2 median (min, max), unless stated otherwise infants (n=16) female, n (%) 10 (62.5) gestational age at birth, weeks 39.9 (37.7, 41.7) weight at birth, kg 3.3 (2.6, 4.0) length at birth,b cm 49.5 (46.0, 55.9) normal apgar score (7 to 10) at 1 and 5 minutes,c n 16 amothers who entered the sampling period; bn=15 (1 infant with missing data); capgar scores range from 0 to 10; scores of 7 to 10 are considered normal. min: minimum; max: maximum; apgar: appearance, pulse, grimace, activity, respiration. table 1. baseline characteristics of mothers and infants conclusions • using a highly sensitive and czp-specific assay, czp levels were below lloq (<0.032 µg/ml) in 13/14 infant blood samples at birth and in all infant blood samples at weeks 4 and 8. • this indicates no to minimal placental transfer of czp from mothers to infants, suggesting a lack of in utero fetal exposure during the third trimester. • no new safety signals were identified in the mothers. aes experienced by the infants did not show any patterns or clusters of events suggesting a specific safety signal in children. • combined with evidence from early exposure,10 these data support continuation of czp treatment throughout pregnancy, if anti-tnf therapy is considered necessary. figure 1. crib study design figure 3. plasma czp concentrations in mothers and infants (n=14 mother-infant pairsa) a2/16 infants were excluded from the per protocol analysis set: 1 due to missing data at birth, and 1 due to implausible pk data at birth (i.e. data not consistent with a pediatric czp pk model, based on the expected range of clearance, volume of distribution, and subsequent elimination half-life); b±24 hours; c±7 days (2 samples not collected); d±7 days. blq: below lloq (<0.032 µg/ml). objective • to accurately measure the level of placental transfer of certolizumab pegol (czp) from mothers to infants using a highly sensitive czp-specific assay. lack of placental transfer of certolizumab pegol during pregnancy: results from crib, a prospective, postmarketing, multicenter, pharmacokinetic study alexa b. kimball,1 xavier mariette,2 bincy abraham,3 ann flynn,4 frauke förger,5 anna moltó,6 rené-marc flipo,7 astrid van tubergen,8 laura shaughnessy,9 jeff simpson,9 marie teil,10 eric helmer,11 maggie wang,9 eliza chakravarty12 1harvard medical faculty physicians at beth israel deaconess medical center, boston, ma; 2université paris-sud, le kremlin-bicêtre, france; 3houston methodist hospital, houston, tx; 4university of utah, salt lake city, ut; 5university of bern, bern, switzerland; 6groupe hospitalier cochin, paris, france; 7centre hospitalier régional universitaire de lille, lille, france; 8maastricht university medical center, maastricht, netherlands; 9ucb pharma, raleigh, usa; 10ucb pharma, slough, uk; 11ucb pharma, brussels, belgium; 12oklahoma medical research foundation, oklahoma city, ok czp plasma concentrations • in all mothers enrolled (n=16), czp plasma levels at delivery were within the expected therapeutic range (median [range]: 24.4 [5.0–49.4] µg/ml). • two infants were excluded from the per protocol analysis set: 1 due to missing data at birth, and 1 due to implausible pk data at birth (i.e. data not consistent with a pediatric czp pk model, based on the expected range of clearance, volume of distribution, and subsequent elimination half-life). • of the remaining 14 infants, 13 had no quantifiable czp plasma levels at birth (<0.032 µg/ml); 1 infant had a minimal czp level at birth of 0.042 µg/ml (infant/mother plasma ratio: 0.0009) (figure 3). • none of the 14 infants had quantifiable czp plasma levels at weeks 4 and 8 (figure 3). of note, 9 of these infants were breastfed while their mothers were taking czp. • of the 16 umbilical cord samples, 1 was excluded due to missing data. of the remaining 15 cords, 3 had quantifiable czp levels (maximum: 0.048 µg/ml). safety and immunogenicity analysis • aes in the mothers were consistent with the known safety profile of czp and pregnancy profile of these underlying diseases (table 2). • serious aes (saes) in the mothers were mild to moderate, except one case of arrested labor and one case of prolonged labor. six saes led to hospitalization; all were resolved except for delivery of a premature baby (table 2). sulfo-tag streptavidina biotin-labeled anti-peg antibody czp tnf-coated electrode fab' peg 100 10 1 0.1 blq c z p c o n c e n tr a ti o n ( µ g /m l ) deliveryb week 4c week 8d lloq=0.032 µg/ml mothers infants • aes experienced by the infants did not show any patterns or clusters of events suggesting a specific safety signal in children (table 2). • four saes were reported in two infants; all were mild to moderate except the infection. all saes were resolved (table 2). • no anti-czp antibodies were detected in the mothers, umbilical cords, or infants at any time point during the study. home health nursing visits screening period sampling period start of pregnancy birth 4 weeks (±7 days) postpartum safety follow-up 8 weeks (±7 days) postpartum 5 weeks (±5 days) after final sample ≤35 days prior to deliverya screening (≥30 weeks pregnant) czp dosing: = czp 200 mg q2w = czp 400 mg q4w primary endpoint: = infant blood sampling (birth) secondary endpoint: = cord blood sampling = mother blood sampling exploratory endpoint: infant blood sampling (4 and 8 weeks) = n=16n=21 alast czp dose given within 35 days prior to delivery. q2w: every 2 weeks; q4w: every 4 weeks. fc17posterucbpharmakimballlackofplacentaltransfer.pdf i n t r o d u c t i o n • �atopic�dermatitis�(ad)�is�a�relapsing,�chronic,�pruritic,�inflammatory�skin�disease� associated�with�gene-environment�interactions,�immune�dysregulation,�and�skin� barrier�dysfunction.1 � –��ad�affects�around�3.2%�of�adults�in�the�usa.2 • �severe�disease�is�often�associated�with�significant�disability,�leading�to�high� socioeconomic�costs�including:�psychological�problems,�significant�sleep�loss,� and�impaired�quality�of�life.3 • �the�current�treatment�approach�for�ad�is�to�reactively�treat�flares. � –��topical�corticosteroids�are�most�frequently�prescribed�for�the�treatment�of�ad;4 however, in patients with moderate-to-severe disease and inadequate response�to�topical�therapy,�more�aggressive�systemic�therapies�are� medically�necessary.5 • �at�present,�the�real-world�treatment�patterns�and�unmet�needs�of�adult�patients� with�moderate-to-severe�ad�are�poorly�quantified�for�patients�treated�with� systemic�therapies. o b j e c t i v e • �to�evaluate�from�a�patient�perspective�the�adequacy�of�systemic�treatment�and� to�document�potential�unmet�needs�in�the�treatment�of�moderate-to-severe�ad.� m e t h o d s • �the�study�was�a�longitudinal�prospective�observational�study�of�adult�patients� with�moderate-to-severe�ad,�receiving�a�systemic�medication�for�the�treatment�of� ad�in�the�previous�6�months. • �study�subjects�were�adult�commercial�health�plan�enrollees�with�ad,�identified� from�the�optum�research�database. • �ad�was�defined�using�international�classification�of�disease,�ninth�or�tenth� revision,�clinical�modification�(icd-9-cm�or�icd-10-cm). • �eligible�study�participants�were�invited�by�mail�to�participate�in�a�baseline�paper� survey,�followed�by�web-based�surveys�at�3,�6,�9,�and�12�months.�monthly� abbreviated�web-based�surveys�were�also�included. • �diagnosis�of�ad,�moderate-to-severe�ad�(during�the�previous�12�months),�and� systemic�medication�use�was�verified�by�patients�at�the�time�they�completed�the� baseline�survey. • �an�informed�consent�statement�was�provided�with�the�paper�survey,�and�consent� for�study�participation�was�implied�when�the�survey�was�returned. inclusion criteria • �aged�≥18�years. • �at�least�one�medical�claim�with�an�icd-9-cm�diagnosis�code�for�ad�(691.8)�or� icd-10-cm�diagnosis�code�(l200,�l2081,�l2082,�l2083,�l2084,�l2089,�l209)� from�a�dermatologist�or�allergist/immunologist�over�the�last�5�years;�or • �at�least�one�medical�claim�with�a�diagnosis�code�for�contact�dermatitis�due�to�an� unspecified�condition�(icd-9:�692.9,�icd-10:�l259)�or�rash�and�other� non-specific�skin�eruption�(icd-9:�782.1,�icd-10:�r21)�from�a�dermatologist�or� allergist/immunologist�over�the�last�5�years;�and at least two non-diagnostic medical�claims�at�least�30�days�apart�with�a�diagnosis�code�for�asthma,�food� allergies,�or�allergic�rhinitis. • �at�least�one�pharmacy�claim�or�medical�claim�over�the�last�6�months�for:�at�least� one�oral�corticosteroid;�at�least�one�injectable�corticosteroid;�at�least�one� phototherapy�treatment;�or�any�immunosuppressant. • �continuous�enrollment�with�both�medical�and�pharmacy�benefits�in�a�large� commercial�us�health�plan�affiliated�with�optum�during�the�past�6�months.� • �able�and�willing�to�complete�surveys. • �self-reported�ad�diagnosis�in�the�patient�survey.� • �moderate-to-severe�ad�over�the�past�12�months�using�the�rajka�and� langeland�criteria.6 exclusion criteria • �participation�in�a�clinical�trial�for�ad�in�the�last�6�months. • �at�least�two�non-diagnostic�medical�claims�at�least�30�days�apart�with�a� diagnosis�code�for�conditions�that�may�be�treated�with�systemic�steroids�during� the�last�5�years. • �at�least�one�pharmacy�or�medical�claim�for�an�immunosuppressant�in�the�last� 5�years�and�at�least�two�non-diagnostic�medical�claims�at�least�30�days�apart�with� a�diagnosis�code�for�conditions�that�may�be�treated�with�immunosuppressants. • �at�least�two�non-diagnostic�medical�claims�at�least�30�days�apart�with�a� diagnosis�code�that�may�be�treated�with�systemic�immunosuppressants�within� the�past�5�years. • �at�least�two�non-diagnostic�claims�at�least�30�days�apart�with�a�code�indicating�a� solid�organ�transplant�over�the�last�5�years. • �surveys�that�were�partially�completed,�ineligible,�returned�too�late,�or�had� non-responses�were�excluded. survey outcomes • �the�baseline�paper�survey�collected�the�following�from�patients: � –��sociodemographic�characteristics:�race,�ethnicity,�marital�status,�education� level,�and�household�income�level. � –��medical�history:�patient�confirmation�of�ad�diagnosis�by�a�healthcare� professional,�age�at�ad�diagnosis,�and�self-reported�disease�severity�using�the� rajka�and�langeland�criteria.6 � –��signs�and�symptoms�of�ad:�patient-reported�flares,�patient-orientated�eczema� measure�(poem)7�and�the�pruritus�numeric�rating�scale�(nrs).8 � –��disease-specific�quality�of�life�assessed�using�the�dermatology�life�quality� index�(dlqi)9�and�work�productivity�assessed�by�the�work�productivity�and� activity�impairment�scale�(wpai).10 � –��prior�and�ongoing�medications�for�ad:�systemic�immunosuppressants�and� corticosteroids,�topical�corticosteroids�and�immunomodulators,�phototherapy,� antibiotics,�and�antihistamines. � –��treatment�satisfaction�using�the�treatment�satisfaction�questionnaire�for� medication�(tsqm-ii).11 statistical analysis • �chi-square�tests�and�t-tests�were�used�for�bivariate�comparisons�of�demographics� and�outcome�measures�based�on�the�distribution�of�the�measure.�spearman’s� rank-order�correlation�analyses�were�conducted�to�examine�the�relationship� between�number�of�flares�and�select�patient-reported�outcome�measures. –��unless�otherwise�specified,�tests�of�significance�were�two-tailed�and�carried� out�at�the�5%�level�of�significance.� r e s u lt s demographics, ad history and medication use • �from�6000�potential�study�participants,�5199�patients�were�excluded�and�801� (13.4%)�were�included�in�the�analysis. � –��mean�age�of�patients�was�45.2�years;�71.8%�were�female;�83.7%�were� caucasian�(table 1).� • �many�patients�(66.3%)�reported�that�they�were�diagnosed�with�ad�after�the�age� of�20. � –��per�the�self-completed�rajka�and�langeland�criteria,�73.7%�of�patients�had� moderate�ad�and�26.3%�had�severe�ad. –���in�the�12�months�prior�to�baseline,�38.3%�of�patients�reported�no�remission,� 35.8%�reported�<3�months�of�remission,�and�25.8%�reported�3�or�more�months� of�remission�(table�1). • �medication�used�within�the�last�month�included:�topical�corticosteroids,�63.6%;� topical�calcineurin�inhibitors,�7.7%;�oral�corticosteroids,�8.5%;�and oral immunosuppressants,�5.0%�(figure 1). a real-world study evaluating adequacy of existing systemic treatments for patients with moderate-to-severe atopic dermatitis (ad-quest): baseline treatment patterns and unmet needs assessment wenhui wei1*, eric ghorayeb2, michael andria3, valery walker4, jingdong chao3, james schnitzer2, martha kennedy3, zhen chen3, angela belland4, john white4, jonathan i. silverberg5 1formerly of sanofi, bridgewater, nj, usa; 2sanofi bridgewater, nj, usa; 3regeneron pharmaceuticals, inc., tarrytown, ny, usa; 4optum, eden prairie, mn, usa; 5northwestern university feinberg school of medicine, chicago, il, usa *current address: regeneron pharmaceuticals, inc., tarrytown, ny, usa presented at the annual winter clinical dermatology conference hawaii, january 12–17, 2018, maui, hawaii previously presented at the 76th annual meeting of the society for investigative dermatology (sid), april 26–29, 2017, portland, oregon table 1. baseline demographic characteristics and ad diagnosis and severity. characteristics total (n = 801) age�(years),�mean�(sd) 45.21�(13.84) n % age group 18–44 363 45.32 45–64 396 49.44 65+ 42 5.24 gender male 226 28.21 female 575 71.79 geographic region northeast 72 8.99 midwest 185 23.10 south 402 50.19 west 142 17.73 hispanic yes 67 8.48 no 723 91.52 race* white�or�caucasian 665 83.65 black�or�african�american 66 8.30 american�indian�or�alaska�native 15 1.89 asian�or�pacific�islander 41 5.16 other 31 3.90 missing 6 – employed† yes 631 78.78 no 170 21.22 age at ad diagnosis under�5�years 99 12.41 5–10�years 59 7.39 11–20�years� 111 13.91 21�years�or�older 529 66.29 missing 3 – ad�severity�categories�(rajka�and�langeland�grading�system) moderate�(4.5–7.5) 590 73.66 severe�(8–9) 211 26.34 ad�severity�score�(rajka�and�langeland�grading�system),�mean�(sd) 6.67�(1.21) total�time�patients�experienced�remission�from�ad no�remission�during�last�12�months 307 38.33 <3�months�of�remission�during�the�last�12�months 287 35.83 3�or�more�months�of�remission�during�the�last�12�months 207 25.84 sd,�standard�deviation.�*respondent�could�select�more�than�one�response;�†employment�status�(working�for�pay)�was�derived�from�the� first�question�in�the�wpai table 2. baseline ad flares. ad flares total (n = 801) n % are�you�currently�experiencing�a�flare�of�your�ad? yes 449 56.20 no 350 43.80 missing 2 – over�the�past�month,�how�many�flares�have�you�experienced? 0 149 18.70 1 186 23.34 2 157 19.70 >2 305 38.27 missing 4 – over�the�past�month,�on�average,�approximately�how�long�did�each�flare(s)�last? <1�week 145 22.34 1�week�to�<2�weeks 205 31.59 2�weeks�to�<3�weeks 117 18.03 3�or�more�weeks 182 28.04 have�you�recovered�from�your�most�recent�flare? i�have�completely�recovered 84 12.96 i�have�partially�recovered 422 65.12 i�have�not�recovered�at�all 142 21.91 over�the�past�month,�how�often�did�you�worry�about�having�a�flare�of�your�ad always 170 21.30 often 188 23.56 sometimes 237 29.70 rarely 136 17.04 never 67 8.40 missing 3 – over�the�past�month,�on�average,�how�worried�were�you�about�your�next�flare? extremely�worried 74 9.28 very�worried 115 14.43 somewhat�worried 283 35.51 not�very�worried 228 28.61 not�at�all�worried 97 12.17 missing 4 – table 3. baseline ad patient-reported outcomes. total (n = 801) n mean (sd) dlqi score* 789 6.44�(6.28) n % dlqi categories no�effect�on�qol 180 22.81 small�effect�on�qol 263 33.33 moderate�effect�on�qol 176 22.31 very�large�effect�on�qol 131 16.60 extremely�large�effect�on�qol 39 4.94 missing 12 – n mean (sd) tsqm score† effectiveness 800 50.08�(24.20) side�effects 799 87.85�(23.31) convenience 796 64.09�(17.53) global�satisfaction 797 60.17�(21.47) wpai score‡ absenteeism�(hours�missed�from�work�in�the�past� 7�days�due�to�ad) 625 0.63�(3.16) number�of�hours�missed�for�those�who�missed� >0�hours�(due�to�ad) 56 7.05�(8.19) percent�impairment�while�working�in�the�past� 7�days�due�to�ad 559 14.74�(21.35) presenteeism (unproductive hours in the past 7�days�due�to�ad) 559 5.53�(8.37) work�productivity�loss�(in�hours)�in�past�7�days� (absenteeism + presenteeism) due to ad 558 6.11�(9.43) percent�impairment�in�regular�daily�activities�in� the�past�7�days�due�to�ad 792 18.88�(24.76) n % work�time�missed�due�to�ad 564 2.11 *dlqi�scores�range�from�0�(no�effect�on�qol)�to�30�(extremely�large�effect�on�qol).�†tsqm�scores�range�from�0–100�where�higher� scores�represent�better�satisfaction.� ‡higher�wpai�scores�indicate�greater�impairment. acknowledgements the�study�was�funded�by�sanofi�and�regeneron�pharmaceuticals�inc.�medical�writing�support�was�provided�by�abby�armitt,�prime,� knutsford,�uk�and�funded�by�sanofi�and�regeneron�pharmaceuticals,�inc. disclosures wenhui�wei�is�a�former�employee�and�current�stockholder�of�sanofi�and�an�employee�of�regeneron�pharmaceuticals,�inc.�eric�ghorayeb� and�james�schnitzer�are�employees�of�and�stockholders�in�sanofi.�michael�andria,�jingdong�chao,�martha�kennedy�and�zhen�chen�are� employees�of�and�stockholders�in�regeneron�pharmaceuticals,�inc.�valery�walker,�angela�belland�and�john�white�are�employees�of� optum,�a�company�that�received�research�funding�for�the�current�study.�jonathan�silverberg�is�a�member�of�an�institution�that�received� research�funding�for�the�current�study. c o n c l u s i o n s • �despite�standard-of-care�treatments,�adults�with�moderate-to-severe�ad�report� high�disease�burden�from�disease�symptoms,�recurrent�flares�and�impaired�qol,� suggesting�significant�unmet�therapeutic�needs. no oral immunosuppressants or corticosteroids no injectable immunosuppressants or corticosteroids no oral or injectable immunosuppressants or steroids injectable immunosuppressants (methotrexate) oral or injectable methotrexate oral corticosteroids any systemic steroids* injectable corticosteroid any systemic immunosuppressant* oral immunosuppressant topical corticosteroids topical calcineurin inhibitors phototherapy antibiotics any antihistamine antihistamines with a prescription antihistamines without a prescription 0 10040302010 60 87.56 95.00 85.16 0.62 1.12 8.49 11.36 4.37 5.12 4.99 63.55 7.74 2.12 4.74 38.20 13.11 32.83o th er m ed ic at io ns fo r a d s ys te m ic m ed ic at io ns fo r a d 7050 80 90within the last month (n = 801) percentage figure 1. baseline ad medication used within the last month. *oral�or�injectable side effects convenience global satisfaction 0 5040302010 60 p < 0.0001 p < 0.0001 p < 0.0001 p < 0.0001effectiveness 58.10 (sd 23.19) 43.86 (sd 23.17) 50.10 (sd 24.22) 91.63 (sd 19.04) 84.86 (sd 25.83) 87.82 (sd 23.33) 61.06 (sd 17.29) 64.14 (sd 17.52) 68.08 (sd 17.04) 66.91 (sd 19.34) 54.95 (sd 21.53) 60.20 (sd 21.42) 908070 100 total currently experiencing a flare not currently experiencing a flare mean tsqm score absenteeism (hours missed from work) number of hours missed for those who missed >0 hours percent impairment while working presenteeism (unproductive hours) work hours lost (in hours) percent impairment in regular daily activities 0 252015105 30 p = 0.071 p = 0.446 p < 0.0001 p < 0.0001 p < 0.0001 p < 0.0001 0.63 (sd 3.16) 0.83 (sd 3.41) 0.38 (sd 2.80) 7.05 (sd 8.19) 6.61 (sd 7.44) 8.67 (sd 10.73) 14.76 (sd 21.38) 20.00 (sd 24.27) 7.78 (sd 14.04) 5.54 (sd 8.38) 7.35 (sd 9.53) 3.12 (sd 5.73) 6.11 (sd 9.44) 8.17 (sd 10.71) 3.39 (sd 6.51) 18.90 (sd 24.79) 25.88 (sd 27.55) 10.03 (sd 17.07) total currently experiencing a flare not currently experiencing a flare mean *tsqm�scores�range�from�0–100�where�higher�scores�represent�better�satisfaction.�†higher�wpai�scores�indicate�greater�impairment� and�are�for�over�the�past�7�days�due�to�ad. figure 3. baseline ad patient-reported outcomes by current ad flare status a) mean tsqm score*; b) mean wpai score†. a) b) l i m i tat i o n s • �this�study�was�a�patient�survey�where�recall�bias�was�a�limitation. • �additionally,�in�the�current�baseline�analysis,�patients’�assessment�of�outcomes� like�dlqi�were�based�on�the�past�7�days�and�may�not�capture�the� comprehensive�impact�of�change�to�ad,�given�the�fluctuation�of�the�disease. • �since�ad-quest�was�a�longitudinal�survey,�the�follow-up�survey�should�provide� more comprehensive understanding�of�the�disease�burden. 28 26 24 22 20 18 16 14 12 10 8 6 4 2 0 n = 799 n = 449 n = 350 10.29 (sd 7.62) 13.50 (sd 6.94) 6.17 (sd 6.38) p o e m s co re * total currently experiencing a flare not currently experiencing a flare 10 9 8 7 6 5 4 3 2 1 0 p ru ri tu s n r s s co re † n = 795 n = 447 n = 348 n = 794 n = 446 n = 348 5.11 (sd 3.22) 6.34 (sd 2.58) 3.52 (sd 3.27) 3.70 (sd 2.78) 4.82 (sd 2.56) 2.26 (sd 2.34) itch at worst moment during 24 hours itch overall (on average) during 24 hours figure 2. baseline ad patient-reported outcomes by current ad flare status: a) poem score; b) pruritus nrs score. *poem�scores�range�from�0�(no�eczema)�to�28�(very�severe�eczema).�the�proposed�banding�for�poem�scores�are:�0–2�(clear/almost� clear);�3–7�(mild);�8–16�(moderate);�17–24�(severe);��25–28�(very�severe).7� †pruritus�nrs�scores�range�from�0�(no�itch)�to�10�(worst�itch�imaginable).�the�proposed�banding�for�nrs�scores�are:�<3�(mild�itch); �>6.9�(severe�itch);�>9.0�(very�severe�itch).8 a) b) patient reported flares, poem, and pruritus nrs • �a�total�of�56.2%�patients�were�currently�experiencing�a�flare,�and�38.3%� experienced�more�than�two�flares�over�the�past�month. � –��of�those�experiencing�at�least�one�flare�over�the�last�month,�65.1%�and�21.9%� had�partial�or�no�recovery�of�their�most�recent�flares�(table 2). • �mean�poem�score�over�the�last�week�was�10.3�(poem�scores�range�from�0–28,� with�higher�scores�indicating�more�severe�eczema),�with�57.6%� reporting�moderate�to�very�severe�symptoms�based�on�poem�scores�of�8�or� greater.�23.3%�of�patients�reported�sleep�disturbance�for�at�least�3�days�out�of� 7�days.�the�mean�pruritus�nrs�score�for�the�worst�itch�during�the�previous� 24�hours�was�5.1�(pruritus�nrs�scores�range�from�0�(no�itch)�to�10�(worst� itch�imaginable). • �at�baseline,�the�number�of�flares�correlated�with�the�poem�categories�and� poem�sleep�disruption�days,�pruritus�nrs�itch�at�worst�moment,�and�pruritus� nrs�overall�itch�(correlation�coefficient�0.5172,�0.4061,�0.4250�and�0.4694,� respectively;�all�p�<�0.001).� • �mean�poem�and�pruritus�nrs�scores�for�worst�itch�and�itch�overall�were� significantly�higher�in�those�experiencing�a�flare�versus�those�not�experiencing� a�flare�(all�p�<�0.001)�(figure�2).�among�those�experiencing�a�flare,�33.2%�of� patients�reported�sleep�disturbance�for�at�least�3�out of�7�days. dlqi, tsqm and wpai • �twenty-two�percent�of�patients�reported�that�ad�had�a�very�or�extremely�large� effect�on�quality�of�life�(qol),�while�the�tsqm�score�for�global�satisfaction�was� 60.2�(tsqm�scores�range�from�0–100,�with�higher�scores�representing�better� satisfaction).�among�working�patients�(78.8%),�work�productivity�loss�in�the�past� 7�days�was�6.1�hours�(table�3). • �outcomes�were�worse�for�patients�experiencing�flares�compared�with�those�not� experiencing�flares�according�to�dlqi�(8.60�vs�3.67,�respectively;�p�<�0.001),�all� four�tsqm�domains�and�wpai,�except�for�hours�missed�from�work�for�all�patients� and�patients�who�missed�work�(figure 3). references 1.�� �boguniewicz�m�et�al.�immunol rev.�2011;242:233–246. 2.�� �silverberg�et�al.�j allergy clin immunol.�2013;132:1132–1138. 3.�� hong�j�et�al.�dermatol ther.�2008;21:54–59. 4.�� �eichenfield�lf�et�al.�j am acad dermatol.�2014;71:116–132. 5.�� �denby�ks�et�al.�curr opin allergy clin immunol.�2012;12:421–426. 6.�� �rajka�g�et�al.�acta derm venereol suppl (stockh). 1989;144:13–14. 7.�� �charman�cr�et�al.�arch dermatol.�2004;140:1513–1519. 8.�� �pereira�mp�et�al.�allergol int.�2017;66:3–7. 9.�� �finlay�ay�et�al.�clin exp dermatol.�1994;19:210–216. 10.���reilly�mc�et�al.�pharmacoeconomics.�1993;4:353–365. 11.���atkinson�mj�et�al.�value health.�2005;8�suppl�1:s9–s24. skin july 2018 volume 2 issue 4 copyright 2018 the national society for cutaneous medicine 261 short communication an eruption of follicular keratotic spicules with alopecia andrew s. desrosiers ma a , anas bernieh md b , adam c. byrd md c , robert t. brodell md c a university of mississippi school of medicine, jackson, ms b department of pathology, university of mississippi medical center, jackson, ms c department of dermatology, university of mississippi medical center, jackson, ms a 62 year-old woman presented with hair loss on her scalp, face, neck, and arms for 2 years. the hair loss was associated with an initial red rash that persisted for several months, and then cleared. the hair loss persisted with dryness, flaking, and itching. there were no known aggravating or alleviating factors and no previous medical problems. the patient was taking no medications or supplements. thyroid stimulating hormone (tsh) and antinuclear antibody (ana) screen were negative. a physical examination revealed follicular keratotic papules and associated hair loss distributed throughout the scalp, postauricular area, and posterior neck (figure 1). figure 1. follicular keratotic papules and associated hair loss on scalp of 62 year-old female. a punch biopsy was performed (figure 2). pathologic examination of a punch biopsy specimen revealed hair follicles demonstrating spongiosis with reticular degeneration and mucin deposition that was confirmed with a colloidal iron stain with appropriate control. surrounding mixed inflammation was noted including numerous eosinophils. there was neither lichenoid inflammation nor amyloid deposition. there were no mycosis cells, pautrier microabscesses, or tagging of lymphocytes along the dermal-epidermal junction. histological and clinical features were consistent with follicular mucinosis. specific features of cutaneous t-cell lymphoma were not identified. figure 1. punch biopsy revealing spongiosis with reticular degeneration and mucin deposition. case report skin july 2018 volume 2 issue 4 copyright 2018 the national society for cutaneous medicine 262 follicular mucinosis (fm), also known as alopecia mucinosa, is an uncommon inflammatory disorder first described by pinkus in 1957. 1 the condition tends to affect children and adults in the third and fourth decades of life. 2 there are two subsets of fm. primary fm is an idiopathic and benign form presenting as an acute or subacute eruption in children or young adults manifesting as pink plaques of grouped follicular papules on the face or scalp associated with alopecia. 3 secondary fm is a chronic condition in older patients associated with atopic dermatitis or cutaneous t-cell lymphoma (particularly mycosis fungoides and sézary syndrome) presenting with a generalized distribution of large plaques. 4 there is no single reliable criterion for differentiating between primary and mycosis fungoides-associated fm. the primary form tends to be associated with younger patients, a solitary or smaller number of plaques, localization around the head and neck, and spontaneous resolution. 2 some cases of primary fm may represent a more indolent, localized form of cutaneous t-cell lymphoma. 5 for many cases of primary fm, spontaneous resolution occurs within 2-24 months. watchful waiting is a reasonable course of action. 2 in some cases patients have benefited from corticosteroids, puva, dapsone, antimalarials, indomethacin, minocycline, isotretinoin, interferon-α-2b, orthovoltage irradiation, or uva1 phototherapy. 2 for secondary fm, treatment should focus on the underlying t-cell lymphoma. in contrast to primary cicatricial alopecia, in which hair follicles are irreversibly destroyed and replaced by fibrous tissue resolution of both types of fm is generally not accompanied by the formation of a true scar, allowing hair regeneration to occur. 6 conflict of interest disclosures: none funding: none corresponding author: andrew desrosiers, ma 2500 north state street, jackson, ms 39216 asdesrosiers@gmail.com references: 1. 1. pinkus h, macaulay w, lund h, delaney j, anderson h, hitch j. alopecia mucinosa: inflammatory plaques with alopecia characterized by root-sheath mucinosis. arch dermatol. 1957;76(4):419-426. 2. 2. bolognia j, jorizzo j, schaffer j, eds. dermatology. philadelphia: elsevier saunders; 2008. 3. 3. brown ha, gibson le, pujol rm, lust ja, pittelkow mr. primary follicular mucinosis: long-term follow-up of patients younger than 40 years with and without clonal t-cell receptor gene rearrangement. j am acad dermatol. 2002;47(6):856-862. 4. 4. rongioletti f, de lucchi s, meyes d, et al. follicular mucinosis: a clinicopathologic, histochemical, immunohistochemical and molecular study comparing the primary benign form and the mycosis fungoidesassociated follicular mucinosis. j cutan pathol. 2010;37(1):15-19. discussion skin july 2018 volume 2 issue 4 copyright 2018 the national society for cutaneous medicine 263 5. cerroni l, fink-puches r, bäck b, kerl h. follicular mucinosis: a critical reappraisal of clinicopathologic features and association with mycosis fungoides and sézary syndrome. arch dermatol. 2002;138:182-189. 6. sellheyer k, bergfeld wf. histopathologic evaluation of alopecias. am j dermatopathol. 2006;28(3):236-259. skin november 2017 volume 1 issue 3 copyright 2017 the national society for cutaneous medicine 173 brief articles sixteen years of a pruritic unilateral axillary eruption: a rare presentation of extramammary paget’s disease amy weiss ba a , robbie drossner md b , mark jacobson, md c a rutgers new jersey medical school, newark, nj b division of dermatology, overlook hospital, summit, nj c departments of medicine, pathology, montefiore medical center/albert einstein college of medicine, bronx, ny an 81 year-old caucasian female presented with a 16 year history of a pruritic rash in the left axilla (figure 1). she reported that it started as a dime-sized red spot and gradually expanded to cover her entire axillary vault. she had been treated with a variety of topical medications, including steroids, pimecrolimus, antifungals, and antiyeast creams. the rash improved but never cleared, despite multiple visits to various internists and dermatologists over the years. patient denied fever, weight loss, malaise and had a negative review of systems. on exam, there was an erythematous erosive plaque with white scale in the left axilla. the lesion measured 7x9 cm. there were no palpable lymph nodes. the right axilla and anogenital regions were clear. a 3.5 mm punch biopsy was performed and sent to the dermatopathologist. skin biopsy revealed a proliferation of large atypical epithelial cells with abundant mucincontaining cytoplasm within the epidermis, both at the dermo-epidermal junction and above it. immunohistochemical staining was positive for cam5.2 and ck7 (figures 2-3) and negative for s100 protein and ck20, abstract extramammary paget’s disease (empd) is a rare intraepithelial adenocarcinoma of apocrine gland-bearing skin. the most common sites affected are the vulva in women and the perinanal, scrotal, and penile regions in men. one quarter of cases are extensions of an underlying visceral malignancy, usually colorectal or urothelial carcinoma. the typical presentation is an expanding erythematous plaque that shows large cells with vacuolated cytoplasm and centrally located nuclei on histology. here we present a case of axillary empd that was incorrectly diagnosed and treated as various forms of dermatitis for over fifteen years. fewer than fifteen cases of axillary empd have been reported in the literature in the past ten years. case report skin november 2017 volume 1 issue 3 copyright 2017 the national society for cutaneous medicine 174 consistent with a diagnosis of extramammary paget’s disease. the patient was referred to an oncologic surgeon for wide local excision of the lesion and primary closure. a ct scan of the chest prior to surgery was negative. surgical margins were clear. at a six month follow up visit, the surgical scar was clear with no evidence of recurrent disease. figure 1: erythematous, scaly, erosive plaque in the left axilla, measuring 7x9 cm figure 2: 40x h&e. intraepithelial proliferation of large atypical cells with large nuclei, prominent nucleoli and abundant pale blue cytoplasm figure 3: biopsy with ck7 stain: highlighting low molecular weight cytokeratins of the tumor cells, not expressed by the surrounding epidermal cells skin november 2017 volume 1 issue 3 copyright 2017 the national society for cutaneous medicine 175 extramammary paget’s disease (empd) is a rare intraepithelial adenocarcinoma of apocrine gland-bearing skin. the vulva in women and the perianal, scrotal and penile regions in men are the most commonly affected sites. 1 empd can be categorized as primary or secondary to an underlying malignancy. in approximately 25% of cases, empd represents extension of an underlying colorectal or urothelial carcinoma, or rarely an adnexal carcinoma. the remainder are primary intraepithelial adenocarcinomas. 2 empd of the axilla is rare, comprising less than 1% of cases. 1 a review of the literature shows fewer than 15 reported cases in the past ten years. a slowly expanding erythematous plaque is a typical clinical presentation. the diagnosis must be confirmed by histological examination. large cells with vacuolated cytoplasm and centrally located nuclei, socalled paget cells, are distinctive, but immunohistochemical staining is important to exclude pagetoid melanoma and squamous cell carcinoma, as well as differentiate between primary and secondary disease. 2 empd rarely metastasizes. however, since it may be associated with an underlying visceral malignancy, most commonly apocrine carcinomas of the bladder, colon, rectum and reproductive organs, a workup for internal malignancies is important. 2 a ct scan of the chest, abdomen, and pelvis, as well as possible pelvic ultrasound, colonoscopy and mammogram, may be indicated, depending on the location of the cutaneous disease. 3 the location of the empd is useful in predicting the risk of an associated cancer. for example, 25-35% of empd in the perianal area is associated with an underlying colorectal cancer. positive staining for cytokeratin 20 and carcinoembryonic antigen in the tissue also raises the suspicion of underlying malignancy. 3 because empd of the axilla is so rare, there are no specific guidelines for visceral malignancy screening. most patients with axillary empd have simultaneous empd in the anogenital region and the other axilla, the so-called “triple paget’s disease.” 1,2 accordingly, ohno, et al. has even recommended skin biopsy from the contralateral axilla and anogenital region, even if they appear clinically normal. 4 treatment options for axillary empd are the same as those used for non-axillary empd, and they include mohs micrographic surgery, wide local excision, radiotherapy, photodynamic therapy, co2 laser ablation as well as the use of topical therapies such as imiquimod 5% cream, topical 5fluorouracil, and retinoic acid. 1-4 the prognosis is good for primary empd confined to the epidermis, and the recurrence rate is low. 1,2 monitoring for early detection of local recurrence is recommended at 6 months and long term, given the multifocal pattern often present in empd. in cases of secondary empd, the prognosis is related to the underlying malignancy. 1-4 in this case, the only workup performed was a chest ct scan based on the location of the cutaneous disease. biopsies of the anogenital region and contralateral axillae were not performed due to patient preference. this case is unusual because of its location and typical in its delay in discussion skin november 2017 volume 1 issue 3 copyright 2017 the national society for cutaneous medicine 176 diagnosis. it illustrates the need for any chronic, eczematous lesion of the axilla to be biopsied. it is impossible to clinically distinguish empd of the axilla from other chronic skin conditions such as eczema, intertrigo, psoriasis, lichen simplex chronicus and candidiasis, making the histopathology critical for diagnosis. additionally, axillary empd may possibly be associated with a higher risk of underlying carcinoma than empd found in other regions, making early detection of this disease even more important. 1 conflict of interest disclosures: none. funding: none. corresponding author: amy weiss, ba 37 normandy drive westfield, nh 07090 (908) 884-6121 arw114@njms.rutgers.edu references: 1. chiu cs, yang ch, chen ch. extramammary paget’s disease of the unilateral axilla: a review of seven cases in a 20-year experience. int j. derm. 2011;50:157–160. 2. lloyd j, flanagan am. mammary and extramammary paget’s disease. j. clin pathol. 2000; 53:742-749. 3. al hallak mn, zouain n. extramammary perianal paget’s disease. case rep in gastroenterol. 2009;3(3):332-337.chanda jj. extramammary paget’s disease: prognosis and relationship to internal malignancy. j am acad dermatol. 1985;13:1009-1014. 4. ohno h, hatoko m, kuwahara m, et al. two cases of unilateral axillary paget’s disease. j dermatol. 1998; 25: 260–263. skin january 2019 volume 3 issue 1 copyright 2018 the national society for cutaneous medicine 31 brief articles widespread erythematous plaques in a multigravid female alex harrison, bs,1 george gibbons, md,2 joseph dyer, do,3 1edward via college of osteopathic medicine, auburn, al 2dermpath diagnostics, tampa, fl 3avail dermatology, fayetteville, ga dermatologic conditions in pregnancy can be attributed to physiological adaptations, changes in pre-existing skin diseases, or development of new dermatologic conditions specific to pregnancy.1,2 although controversy exists, there is an ill-defined group of pruritic conditions that are considered pregnancy-specific skin dermatoses, which include pemphigoid gestationis, polymorphic eruption of pregnancy (pep), intrahepatic cholestasis of pregnancy, atopic eruption of pregnancy, and generalized pustular psoriasis of pregnancy (gppp).3 excluding intrahepatic cholestasis of pregnancy, which presents with secondary skin lesions like excoriations, prurigo nodularis, and occasionally jaundice, these conditions can often manifest as widespread erythematous plaques and papules. when these conditions occur simultaneously with chronic dermatologic conditions, such as herpes labialis, correct diagnosis can be elusive. because pemphigoid gesationis and gppp carry potential risk to the fetus, cutaneous eruptions in pregnancy should prompt immediate consultation and evaluation by a dermatologist.4 prognosis is typically favorable with early recognition and management. delayed or misdiagnosis may result in placental insufficiency, preterm delivery, growth restrictions, miscarriage, and stillbirth.4,5,6 a 35-year-old g2p1 caucasian female at 36 weeks gestation with chronic hypertension and history of herpes labialis presented with a pruritic eruption for two weeks. the eruption began on her abdomen involving the striae and subsequently generalized. she reported dysphagia but no other systemic complaints. physical exam showed erythematous plaques and papules without when dermatological eruptions present diagnostic uncertainty, there is cause for concern, especially when treating the mother of an unborn child. while cutaneous outbreaks in pregnancy can be benign, suspicious disseminating rashes should warrant further investigation. we present a case of generalized pustular psoriasis of pregnancy that manifested in an atypical fashion and could have been overlooked without the utilization of biopsy and histopathological analysis. due to reports of unfavorable maternal-fetal outcomes, prompt evaluation and treatment is critical. abstract introduction case report skin january 2019 volume 3 issue 1 copyright 2018 the national society for cutaneous medicine 32 figure 1: erythematous plaques present on the axilla. bullae, pustules or scales distributed on upper and lower extremities, truncal and intertriginous skin (figure 1), and the left labia majora. the rash included palmoplantar involvement. a small superficial erosion was also noted on the soft palate. the clinical differential diagnosis included erythema multiforme, pep, herpes gestationis, and psoriasis. the patient completed a prednisone taper and was started on topical steroids with no improvement over two weeks. two punch biopsies were obtained, and histopathology revealed psoriasiform epidermal hyperplasia with mounds of parakeratosis containing neutrophils with slight spongiosis and no increase of eosinophils (figure 2). the other showed spongiform pustule formation with parakeratosis and minimal spongiosis with dilated tortuous blood vessels in dermal papillae (figure 3). the patient was monitored closely in conjunction with her obstetrician. significant laboratory studies revealed mild hypocalcemia of 8.6 mg/dl (reference range 8.7-10.2 mg/dl), leukocytosis of 13.3 x10e3/ul (reference range 3.4-10.8 x 10e3/ul) and a neutrophilia of 9.2 x 10e3/ul (reference range 1.4-7.0 x 10e3/ul). considering the new evidence, a diagnosis of gppp was made. the patient was treated with topical steroids and underwent cesarean section due to hypertension at 38 weeks gestation. a healthy baby girl was delivered. over a two-month period, the treatment regimen consisted of oral prednisone 20mg, mometasone 0.1% topical cream, clobetasol 0.05% topical cream, and triamcinolone acetonide 0.1% topical cream. the pruritic eruption resolved eight weeks post-partum. figure 2: psoriasiform epidermal hyperplasia with mounds of parakeratosis containing neutrophils with slight spongiosis and no increase of eosinophils. figure 3: spongiform pustule formation with parakeratosis and minimal spongiosis with dilated tortuous blood vessels in dermal papillae. skin january 2019 volume 3 issue 1 copyright 2018 the national society for cutaneous medicine 33 generalized pustular psoriasis of pregnancy, formerly known as impetigo herpetiformis, is considered a rare variant of generalized pustular psoriasis that can occur anytime during pregnancy, but often presents in the third trimester. although the etiology is unclear, elevated serum progesterone, hypocalcemia, stress and infections have been suggested as potential triggers.7 an elevation in cytokines due to mutations in il36 receptor antagonist has also been suggested to contribute to the inflammatory response seen in gppp.8 the rash of gppp is characterized by sterile pustules at the periphery of erythematous plaques initially arising from intertriginous areas of the body with subsequent involvement of the trunk and limbs.1 our patient presented in a similar fashion in terms of progression, but interestingly never revealed pustules throughout the course of disease. in addition to oral herpetic lesions, she displayed an acral eruption involving the palms and soles, which are usually spared in gppp. initially, erythema multiforme was considered given the history, distribution, and contemporaneous active herpes labialis. polymorphic eruption of pregnancy was also possible given it is much more common and characteristically involves the striae. despite the lack of bullae, pemphigoid gestationis is a diagnostic consideration that must be ruled out, as it too can present as urticarial plaques or papules surrounding the umbilicus and increases the risk of maternal-fetal harm.4 unlike the other pregnancy-specific dermatoses, gppp is often accompanied by systemic signs and symptoms of fever, malaise, vomiting, diarrhea, convulsions, delirium and elevated markers of inflammation.7 our patient did not exhibit any of these, except mild dysphagia. when presenting with non-specific erythematous papules and plaques without prominent systemic symptoms, gppp could easily be misdiagnosed and progress untreated. clinical history and morphology can help differentiate gppp from similar dermatoses, but ultimately punch biopsy with histopathologic analysis is recommended for definitive diagnosis.4,9 the characteristic spongiform pustules containing neutrophils along with psoriasiform epidermal hyperplasia and parakeratosis were seen in our patient despite the absence of clinical pustules. current literature suggests early treatment with systemic corticosteroids or low dose cyclosporine for immunosuppression.7 infliximab, a tnf-α inhibitor, has also been used in a minority of cases as a first-line agent for severe forms.7 our patient gradually improved over a two-month period. early in the course, she completed a prednisone taper but was subsequently managed with topical mometasone and clobetasol creams. numerous publications note rapid resolution of disease following delivery, but some reports suggest gppp may recur in subsequent pregnancies.10,11,12 in some instances it has been reported that the pustular form evolved into classic psoriatic lesions.10 differing opinions exist as to whether personal or family history of psoriasis confers increased risk of gppp.7,10,11,12 our patient had no personal or family history and reported complete resolution eight weeks postpartum with only faint post-inflammatory erythema. discussion skin january 2019 volume 3 issue 1 copyright 2018 the national society for cutaneous medicine 34 generalized pustular psoriasis of pregnancy is an uncommon dermatosis of pregnancy often associated with obscure clinical and laboratory findings. keeping gppp on the differential of pruritic eruptions presenting with erythematous papules and plaques is important, even when no pustules are appreciable. close management and follow up is recommended as fetal harm could be imminent. our case sheds light on gppp, illustrating a rare condition in attenuated form. utilizing biopsy and histopathological analysis is critical in the diagnostic pursuit, as we identified gppp despite the absence of pustules and averted harm to mother and child. conflict of interest disclosures: none. funding: none. corresponding author: alex harrison edward via college of osteopathic medicine auburn, al taharrison@auburn.vcom.edu references: 1. wamalwa e. recurrent impetigo herpetiformis: case report. pan african medical journal. 2017;27. 2. vaughan jones s, ambros-rudolph c, nelson-piercy c. skin disease in pregnancy. bmj. 2014;348(jun03 3):g3489-g3489. 3. sachdeva s. the dermatoses of pregnancy. indian journal of dermatology. 2008;53(3):103. 4. lehrhoff s, pomeranz m. specific dermatoses of pregnancy and their treatment. dermatologic therapy. 2013;26(4):274-284. 5. lotem m, katzenelson v, rotem a, hod m, sandbank m. impetigo herpetiformis: a variant of pustular psoriasis or a separate entity?. journal of the american academy of dermatology. 1989;20(2):338-341. 6. oumeish o. some aspects of impetigo herpetiformis. archives of dermatology. 1982;118(2):103-105. 7. trivedi m, vaughn a, murase j. pustular psoriasis of pregnancy: current perspectives. international journal of women's health. 2018;volume 10:109115. 8. kar s, krishnan a, shivkumar pv. pregnancy and skin [published online august 28, 2012]. j obstet gynaecol india. 2012;62:268-275. 9. goldberg green m, bragg j, rosenman k, keltz pomeranz m. pustular psoriasis of pregnancy in a patient whose dermatosis showed features of acute generalized exanthematous pustulosis. international journal of dermatology. 2009;48(3):299-303. 10. mansouri b, benjegerdes k, hyde k, kivelevitch d. pustular psoriasis: pathophysiology and current treatment perspectives. psoriasis: targets and therapy. 2016;volume 6:131-144. 11. vena g, cassano n, bellia g, colombo d. psoriasis in pregnancy: challenges and solutions. psoriasis: targets and therapy. 2015;:83. 12. flynn a, burke n, byrne b, gleeson n, wynne b, barnes l. two case reports of generalized pustular psoriasis of pregnancy: different outcomes. obstetric medicine. 2016;9(2):55-59. conclusion mailto:taharrison@auburn.vcom.edu this initial demographic analysis of patients with advanced cscc receiving cemiplimab in real-world practice indicates that most patients were male and elderly, with ~20% being immunosuppressed or immunocompromised to varying degrees. only 54.1% of cases had multi disciplinary input in their disease management. these data suggest that there are varying factors affecting advanced cscc treatment decisions in a real-world clinical setting. future analyses will provide additional outcome measures from c.a.s.e. including patient experience, safety outcomes, and effectiveness of cemiplimab in the real-world setting. synopsis • cutaneous squamous cell carcinoma (cscc) is one of the most commonly diagnosed cancers worldwide and incidence rates are increasing.1,2 • most early cases are typically treated with curative surgery.3 however, a small percentage of patients develop locally advanced cscc, that is not amenable to curative surgery or curative radiotherapy (rt).4 • until recently, patients with advanced cscc, who were not candidates for curative surgery or radiation, had poor prognosis.5,6 • cemiplimab is a high-affinity, monoclonal antibody that blocks programmed cell death (pd)-1 binding to pd-ligand (l)1 and pd-l2 and has demonstrated substantial antitumor activity in patients with advanced cscc.4, 7-9 • cemiplimab (cemiplimab-rwlc in the us) is approved by the european medicines agency and is the first pd-1 inhibitor approved by the us food and drug administration for the treatment of patients with locally advanced or metastatic cscc who are not candidates for curative surgery or curative radiation.10,11 • limited data exist on the clinical characteristics, management, disease progression and survivorship of patients with advanced cscc in real-world clinical practice. objectives • patients receiving cemiplimab in the real world will likely have their treatment initiated at various timepoints and at different stages of their disease evolution. • cemiplimab-rwlc survivorship and epidemiology (c.a.s.e.) study aims to evaluate the effectiveness, safety, disease evolution, survivorship, and quality of life (qol) in patients with advanced cscc treated with cemiplimab in a real-world setting. • here, we describe baseline demographics for the first set of patients currently enrolled in the c.a.s.e. study. methods • c.a.s.e. is a prospective, multicenter, longitudinal study evaluating the clinical activity, safety, disease evolution, survivorship, and qol in adult patients with advanced cscc who initiate treatment with cemiplimab, with the primary data collection in real-world clinical settings. • key endpoints include effectiveness of cemiplimab treatment, safety, patient-reported outcomes, treatment adherence, and health resource utilization. • patient-reported outcomes collected: the european organisation for research and treatment of cancer (eortc) qol questionnaire (qlq-c30), eortc qlq-eld14, skin care index, pain numerical rating scale, and sun exposure behaviour inventory. • demographic and baseline data from the first set of patients enrolled in the c.a.s.e. study were analyzed and are presented here. demographics, prior therapies, and reasons for cemiplimab treatment: prospective cemiplimab-rwlc survivorship and epidemiology (c.a.s.e.) study in patients with advanced cutaneous squamous cell carcinoma guilherme rabinowits,1 jade homsi,2 mina nikanjam,3 rhonda gentry,4 john strasswimmer,5 suraj venna,6 michael r. migden,7 sunandana chandra,8 emily ruiz,9 haixin r. zhang,10 jennifer mcginniss,10 alex seluzhytsky,11 jigar desai10 1department of hematology and oncology, miami cancer institute/baptist health south florida, miami, fl, usa; 2division of hematology/oncology, university of texas southwestern medical center, dallas, tx, usa; 3division of hematology and oncology, university of california san diego, ca, usa; 4carti cancer center, little rock, ar, usa; 5college of medicine (dermatology) and college of sciences (biochemistry), florida atlantic university, fl, usa; 6inova schar cancer institute melanoma center, fairfax, va, usa; 7departments of dermatology and head and neck surgery, university of texas md anderson cancer center, houston, tx, usa; 8division of hematology oncology, northwestern university feinberg school of medicine, chicago, il, usa; 9brigham and women’s hospital, boston, ma, usa; 10regeneron pharmaceuticals, inc., tarrytown, ny, usa; 11sanofi, cambridge, ma, usa. table 1. patients demographics n (%) advanced cscc (n=61) median age, years (range) 78.0 (50–98) <65 years 9 (14.8) ≥65 – <75 years 16 (26.2) ≥75 – <85 years 19 (31.2) >85 years 17 (27.9) male 45 (73.8) race, white 59 (96.7) ecog performance status 0 14 (23.0) 1 35 (57.4) 2 4 (6.6) locally advanced cscc 34 (55.7) metastatic cscc 27 (44.3) ecog, eastern cooperative oncology group. table 2. patient and tumor characteristics n (%) advanced cscc (n=61) immunocompromised or immunosuppressed* 13 (21.3) solid organ transplant recipient 3 (4.9) extensive actinic keratosis 20 (32.8) perineural invasion 13 (21.3) histological differentiation moderately differentiated 23 (37.7) well differentiated 14 (23.0) poorly differentiated 12 (19.7) unknown 12 (19.7) *immunocompromised refers to patients who have an autoimmune disease, who have received a solid organ transplant, allogeneic bone marrow transplant, or who have a history of treated or active hematologic malignancies. immunosuppression refers to patients with chronic steroid use or who use chronic immunosuppressive agents. references 1. rogers hw et al. jama dermatol. 2015;151:1081–1086. 2. leiter u et al. j invest dermatol. 2017;137:1860–1867. 3. jennings l and schmults cd. j clin aesthet dermatol. 2010;3:39–48. 4. migden mr et al. n engl j med. 2018;379:341–351. 5. schmults cd et al. jama dermatol. 2013;149:541–547. 6. weinberg as et al. dermatol surg. 2007;33:885–899. 7. burova e et al. mol cancer ther. 2017;16:861–870. 8. migden mr et al. j clin oncol. 2019;37:6015–6015. 9. rischin d et al. j immunother cancer. 2020;8:e000775. 10. regeneron pharmaceuticals, inc. libtayo® [cemiplimab-rwlc] injection full us prescribing information. available from: https://www.accessdata. fda.gov/drugsatfda_docs/label/2018/ 761097s000lbl.pdf. accessed july 13, 2020. 11. european medicines agency. libtayo: epar product information. available from: https://www.ema.europa. eu/en/documents/product-information/libtayo-eparproduct-information_en.pdf. accessed august 24, 2020. acknowledgments the authors would like to thank the patients, their families, all other investigators, and all investigational site members involved in this study. the study was funded by regeneron pharmaceuticals, inc. and sanofi. editorial writing support was provided by jenna lee of prime, knutsford, uk, funded by regeneron pharmaceuticals, inc. and sanofi. disclosures guilherme rabinowits reports consulting/advisory role for emd serono, pfizer, sanofi, regeneron pharmaceuticals, inc., and merck and castle, and stock/other ownership interests from syros pharmaceuticals and regeneron pharmaceuticals, inc. jade homsi reports personal fees from sanofi, novartis, and regeneron pharmaceuticals, inc. mina nikanjam reports support for running clinical trials from regeneron pharmaceuticals, inc., and support for running industrysponsored clinical trials from idera pharmaceuticals, bms, novartis, and immunocore. rhonda gentry is a principal investigator for the c.a.s.e. registry. john strasswimmer reports a grant as an investigator for the clinical trial. suraj venna declares no conflict of interest. michael r. migden reports honoraria from regeneron pharmaceuticals, inc., sanofi, novartis, genentech, eli lilly, and sun pharma. sunandana chandra reports consulting/advisory role for sanofi-genzyme, bristol-myers squibb, emd serono, biodesix, array biopharma, novartis, and regeneron pharmaceuticals, inc., and other conflicts with sanofi-genzyme, bristol-myers squibb, emd serono, biodesix, and regeneron pharmaceuticals, inc. emily ruiz reports consulting fees from regeneron pharmaceuticals, inc., leo pharma, checkpoint therapeutics, and pellepharma. haixin r. zhang, jennifer mcginniss, and jigar desai are employees and stockholders of regeneron pharmaceuticals, inc. alex seluzhytsky is an employee of sanofi genzyme. results baseline demographics and disease characteristics • as of january 31, 2020, 61 patients were enrolled (median age: 78.0 years [interquartile range: 70–86]); 73.8% were male and 96.7% were caucasian (table 1). table 3. prior treatments n (%) advanced cscc (n=61) any prior cscc surgery 46 (75.4) number of prior cscc-related surgery 1 17 (27.9) 2 14 (23.0) 3 6 (9.8) >3 9 (14.8) any prior rt 25 (41.0) number of prior cscc-related rt 1 18 (29.5) 2 6 (9.8) ≥3 1 (1.6) without any prior cscc systemic therapy (1l) 38 (62.3) any prior cscc systemic therapy (2l+) 23 (37.7) prior systemic therapy setting metastatic disease 12 (19.7) adjuvant 7 (11.5) chemotherapy with concurrent rt 2 (3.3) neoadjuvant 2 (3.3) number of prior cscc systemic therapies 1 15 (24.6) 2 5 (8.2) ≥3 3 (4.9) 1l, first-line; 2l, second-line. • the majority of patients, for whom staging tool data were provided, were classified using the american joint committee on cancer staging manual, 8th edition. the most common cancer stages at initial diagnosis were t3 and t4a (4.9% each). baseline tumor characteristics • cscc tumors were classified histologically as well differentiated in 23.0% of patients, moderately differentiated in 37.7%, poorly differentiated in 19.7%, and unknown in 19.7% (table 2). • tumors in 21.3% of patients had perineural invasion and 8.2% had histological heterogeneity. prior therapies • most patients had received prior cscc therapy, 75.4% had prior cscc-related surgery, and 41.0% received cscc-related rt (table 3). multidisciplinary management and factors affecting cemiplimab treatment decisions • fifty-four percent of patients had multidisciplinary input in their advanced cscc management. • reasons for cemiplimab treatment are shown in figure 2. figure 1. summary of advanced cscc in patients in real-world practice head and neck 68.9% 29.5%upper and lower extremities 9.8%thorax and abdomen 4.9%not known • this initial demographic analysis of patients with advanced cscc receiving cemiplimab in real-world practice indicate ~20% being immunosuppressed or immunocompromised to varying degrees. • only 54.1% of cases had multi-disciplinary input in their disease management. • data suggest there are varying factors affecting advanced cscc treatment decisions in a real-world clinical setting. • fifty-six percent of the patients had locally advanced cscc and 44.3% had metastatic cscc (table 1). • approximately 20% of patients were immunocompromised or immunosuppressed, including 4.9% who had solid organ transplant (table 2). • the most common current cscc tumor location was head and neck (68.9%) (figure 1). summary and conclusion figure 2. reasons for cemiplimab initiation* 6.6 4.9 locally advanced cscc not amenable for curative surgery or radiation not a candidate for curative surgery metastatic local-regional disease distant metastatic disease patient preference not a candidate for curative radiation other 34.4 29.5 23 23 14.8 40 35 30 25 20 15 10 5 0% o f p a ti e n ts ( to ta l = 6 1 ) *more than one reason for cemiplimab initiation could be given for a single patient. presented at the 2020 fall clinical dermatology conference, october 29–november 1, virtual scientific meeting (encore of esmo 2020 poster presentation). skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 228 in-depth review verrucous carcinoma arising secondary to diabetic foot lesions: a systematic review of the literature kayla neville, ms1, aleksandar obradovic, mphil2,3 1new york college of podiatric medicine, new york, ny 2department of systems biology, columbia university irving medical center, new york, ny 3columbia university center for translational immunology, new york, ny diabetic foot ulcers are a common complication of chronic uncontrolled diabetes, and the lifetime incidence of foot ulcers is estimated to affect 19% to 34% of people with diabetes.1 diabetic foot ulceration is often complicated by other diabetic symptoms, including severe peripheral neuropathy, peripheral arterial disease, and systemic immunosuppression.2 foot ulcers place patients at significant risk of infection, as more than half of ulcers become infected,3 potentially leading to sepsis or lower limb amputation in approximately 20% of moderate or severe diabetic foot infections.1,4,5 therefore, management of chronic diabetic foot ulcers comprises represents a significant area of concern in primary care of diabetic patients. a rare and often unappreciated sequelae of diabetic foot ulceration is malignant transformation resulting in verrucous carcinoma. verrucous carcinoma is classically considered a variant of squamous cell carcinoma, which forms painful lesions marked by an exophytic appearance, with deep invasion into local underlying structures.6,7 ackerman first described verrucous carcinoma in the oral cavity, associated with chewing tobacco,7 and verrucous carcinoma of the oral cavity has been so closely associated with the use of snuff and chewing tobacco that is has been abstract verrucous carcinoma is classically considered a variant of squamous cell carcinoma, most commonly occurring in the oral cavity in association with snuff and chewed tobacco. however, the association between verrucous carcinoma of the foot and diabetes is less well known. this study presents a systematic review of all articles containing the search term “verrucous carcinoma” and “diabetic foot ulcer” in the abstract or title that have been published in pubmed before september 2020. the requirement for inclusion in our report were that the patient data had been documented in a case‐ related manner and the patient diagnosed with verrucous carcinoma secondary to diabetic foot lesion. seven descriptions of verrucous carcinoma presenting in patients with diabetic foot ulcers were presented across six case reports, and clinical case descriptions are collected here along with treatment outcomes, where available, and discussion of common mimics of verrucous carcinoma of the foot. due to treatability and potential for extensive invasion of local structures requiring resection with wide margins, verrucous carcinoma should be carefully considered in the differential diagnosis of a warty foot lesion in the setting of the diabetic foot. introduction skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 229 called the “snuff dipper’s cancer”.8 however, verrucous carcinoma has been reported to arise outside of the oral cavity in the larynx, the genitalia, and the foot.9 the association between verrucous carcinoma of the foot and diabetes is less well known. here we have conducted a systematic review of literature describing verrucous carcinoma developing secondary to a diabetic foot ulcer. this is an important item on differential diagnosis of dermatologic deformity secondary to diabetic foot ulceration, particularly as the warty appearance of these carcinomas may mimic more common foot pathology. verrucous carcinoma, when diagnosed early, is treatable, but any delay in treatment may increase the degree of local invasion, and it therefore should not be overlooked as a diagnosis. this article represents the most comprehensive review to date of published cases describing verrucous carcinoma arising secondary to diabetic foot ulcers, and provides important insights into the presentation and management of this rare complication of diabetes. we retrieved all articles containing the search term “verrucous carcinoma” and “diabetic foot ulcer” in the abstract or title that had been published in pubmed (www.pubmed.com) before september 2020. until that time, there had been no systematic reviews or meta-analyses analyzed following prisma guidelines.10 sixteen publications were analyzed in more detail, of which six met the requirements to be included in our review. the selection was made by two authors (kn and ao). there were no discrepancies in the lists of articles selected by the two authors. the requirement for inclusion in our report were that the patient data had been documented in a case‐related manner and the patient diagnosed with verrucous carcinoma secondary to diabetic foot lesion. one case of carcinoma cuniculatum11 and one case of ackerman carcinoma12 were included in our analysis, as these are classified as alternate names for verrucous carcinoma.6 one case report13 included two separate cases of verrucous carcinoma secondary to diabetic ulcer in the same patient, for a total of seven such cases across six case reports. finally, we did not include articles that described patients with different disorders such as verrucous skin lesions, verrucous hyperplasia, etc. that were not verrucous carcinoma. data collected included gender, age at the time of diagnosis, comorbidities, lesion location and size, lesion duration prior to verrucous carcinoma diagnosis, histological and gross pathological features, treatment approach, and recurrence status. a quantitative meta‐analysis of outcomes to treatment was not possible based on the limited number of total reported cases in the literature and variations in longitudinal follow-up. diabetes history patients included both men11,14,15,16 and women,12,13 with ages ranging from 44 to 72 years old (table 1). across the six reported cases, all patients had a past history of diabetic foot ulcers followed by histopathological confirmed diagnosis of verrucous carcinoma arising in the region of the ulcer. only two of six studies reported hba1c as an objective metric of diabetes control (case 1 hba1c = 5.9%12, case 3 hba1c=7.7%14). cases did not uniformly describe the severity of diabetes, though 5/6 cases specify that the patient’s diabetes was poorly controlled with several diabetic methods results skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 230 table 1. summary of patient characteristics. demographics diabetes history lesion location lesion duration treatment approach recurrence case 1: dörr et al. 72 y/o female peripheral artery disease, neuropathy, stage g3ba2 nephropathy, previous partial amputations and revascularizations of the foot r medial foot 8 years -primary tumor excision -second resection with tumor free margins -split-skin graft and negative pressure wound therapy no long-term follow-up case 2: di palma et al. 44 y/o female uncontrolled type 2 diabetes with severe peripheral neuropathy in both feet r plantar 1st mtp l plantar 5th mtp ~1 year ~5 months -primary wide excision -secondary mohs resection -mohs resection recurrence at 14 months, no longerterm follow-up no long-term follow-up case 3: priesand et al. 62 y/o male type 1 diabetes, neuropathy with renal insufficiency, hypertension, hyperlipidemia, diabetic retinopathy, multiple digital amputations l plantar 1st mtp 1 month -wide excision with tumor-free margins -partial first ray and hallux amputation no long-term follow-up case 4: nakamura et al. 66 y/o male insulin-dependent diabetes, neuropathy r sole 6 years -excision with 1 cm margin no recurrence at 12 months case 5: penera et al. 44 y/o male uncontrolled type 2 diabetes r dorsal 1st mtp 1 year -wide excision -full thickness skin graft no recurrence at 12 months case 6: lozzi et al. 72 y/o male 15-year history of diabetes mellitus r sole 6 years -tumor excision no recurrence at 36 months complications including: diabetic neuropathy (n=4), kidney manifestations (n=2), and previous partial amputations (n=2). table 1 lists the complications detailed in each case. no patients were described as having a history of cutaneous malignant tumors or other predisposing risk factors, with the exception of case 1 who admitted to smoking, nor were they described as taking any immunosuppressive medications (i.e. steroids, chemotherapy, etc). presentation and timeline carcinomatous lesions arose from foot ulcers ranging in size from 1 to 7cm in width, all occurring in the forefoot. patient ulcers had a peripheral hyperkeratotic border with subsequent wart or cauliflower-like transformation. malodorous secretions were described in several cases,12,13,16 although one case specifically noted a lack of malodor or drainage.14 verrucous carcinoma was diagnosed over a very short or long period following initial ulcer development, presenting in a range from 1 month14 to 8 years.12 only a single patient13 reported pain in the lesion, with the rest reporting painless presentation throughout the disease course, a finding which may be explained by concurrent peripheral neuropathy. case 3 skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 231 illustrates that it is possible for verrucous carcinoma to develop even after a previously active ulcer is considered healed and closed, as carcinomatous transformation in this patient was noted at the 1 month follow up appointment post wound closure.14 presentation was primarily unilateral, with the exception of a single patient who developed carcinomatous transformation in an ulcer of the left foot after previous transformation and treatment of a verrucous carcinoma arising from an ulcer of the right foot.13 diagnosis and treatment verrucous carcinoma significantly overlaps in presentation with common foot dermatopathology, and was misdiagnosed as a straightforward diabetic foot ulcer (cases 1, 2, 3, 5), verrucous skin lesions on the feet in the setting of diabetic neuropathy (case 4), and plantar wart (case 6). however, wound debridement and cryotherapy were ineffective in treatment of verrucous carcinoma. lesions were diagnosed following biopsy, and definitive surgical treatment included excision of the lesion with tumor-free margins, curative in five of the six clinical cases, with varying length of follow-up. however, case 2 experienced recurrence of the lesion 14 months after primary excision, and thus a mohs surgery was performed on the recurrent lesion and as primary treatment for the subsequent verrucous carcinoma observed on the contralateral foot in that patient. this article presents a comprehensive review of the literature to date describing malignant transformation of diabetic foot ulcers into verrucous carcinoma, and provides important insights into the presentation and treatment of this rare diabetic complication. to date, descriptions of verrucous carcinoma in the literature have been sparse and potentially misleading in the context of diabetes, describing a classic clinical presentation of painful ulcers most often localized in the throat.6,7,8 cases of chronic diabetic foot ulcers resulting in verrucous carcinoma of the foot are comparatively under-appreciated. further study of this transformation is needed to determine molecular drivers and predictors of cancer development among patients, and we have collected here the clinical information on these cases available to date. critically, we find that among 6 described cases of diabetic foot ulcer resulting in verrucous carcinoma, only a single patient reported pain in the area of the lesion. therefore, concurrent diabetic neuropathy effectively disguises the typical presentation of this carcinoma. instead, reported cases describe warty or cauliflower like lesions arising over months to years following development of diabetic foot ulcers with no associated pain. this presentation mimics a range of more common dermatological diagnoses including plantar warts. however, it is unresponsive to the first-line treatments for these more benign diagnoses including cryotherapy and wound debridement. clinically, patients presenting with warty lesions in the setting of chronic diabetic foot ulcers and refractory to repeated first-line plantar wart treatment should be promptly biopsied for pathological assessment of verrucous carcinoma as a “do-not-miss” diagnosis. reports suggest effectiveness of surgical intervention in such cases, with 5 out of 6 patients cured by total excision of the lesion with tumor-free margins. a single patient required mohs surgery for curative treatment, which was subsequently applied in the first line on a recurrent tumor in the contralateral foot, but the relative rarity of discussion skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 232 this presentation is difficult to assess from the extent of current literature. increased awareness of verrucous carcinoma as a consequence of diabetic ulceration will result in larger cohorts of reported patients and their response to varying treatment approaches, enabling more comprehensive assessment of excision vs. mohs surgery as a first line surgical approach. most importantly, physicians should strongly consider the possibility of malignant transformation in chronic diabetic foot ulcers as a mimic of more benign foot pathology in any treatment-refractory cases, since surgical therapy appears effective, and early intervention in these cases may greatly reduce the degree of local tissue invasion and subsequent post-surgical morbidity. conflict of interest disclosures: none funding: none corresponding author: kayla neville, ms new york college of podiatric medicine 53 e 124th st, new york, ny 10035 phone: 631-456-9961 email: kneville2023@nycpm.edu references: 1. armstrong dg, boulton aj, bus sa: diabetic foot ulcers and their recurrence. new england journal of medicine 376: 2367, 2017. 2. nathan dm: long-term complications of diabetes. new england journal of medicine 328: 1676, 1993. 3. prompers l, huijberts m, apelqvist j, et al.: high prevalence of ischaemia, infection and serious comorbidity in patients with diabetic foot disease in europe. baseline results from the eurodiale study. diabetologia 50: 18, 2007. 4. lipsky ba, berendt ar, cornia pb, et al.: 2012 infectious diseases society of america clinical practice guideline for the diagnosis and treatment of diabetic foot infections. clinical infectious diseases 54: e132, 2012. 5. lavery la, armstrong dg, wunderlich rp, et al.: diabetic foot syndrome: evaluating the prevalence and incidence of foot pathology in mexican americans and non-hispanic whites from a diabetes disease management cohort. diabetes care 26: 1435, 2003. 6. devaney ko, ferlito a, rinaldo a, et al.: verrucous carcinoma (carcinoma cuniculatum) of the head and neck: what do we know now that we did not know a decade ago?. european archives of oto-rhino-laryngology 268: 477, 2011. 7. ackerman lv: verrucous carcinoma of the oral cavity. surgery 23: 670, 1948. 8. santoro a, pannone g, contaldo m, et al.: a troubling diagnosis of verrucous squamous cell carcinoma (“the bad kind” of keratosis) and the need of clinical and pathological correlations: a review of the literature with a case report. journal of skin cancer 2011: 370605, 2011. 9. kraus ft, perez‐mesa c: verrucous carcinoma. clinical and pathologic study of 105 cases involving oral cavity, larynx and genitalia. cancer 19: 26, 1966. 10. moher d, liberati a, tetzlaff j: preferred reporting items for systematic reviews and metaanalyses: the prisma statement. plos med 6: e1000097, 2009. 11. lozzi gp, peris k: carcinoma cuniculatum. cmaj 177: 249, 2007. 12. dörr s, lucke-paulig l, vollmer c, et al.: malignant transformation in diabetic foot ulcers—case reports and review of the literature. geriatrics, 4: 62. 2019 13. di palma v, stone jp, schell a, et al.: mistaken diabetic ulcers: a case of bilateral foot verrucous carcinoma. case reports in dermatological medicine 2018: 4192657, 2018. 14. priesand sj, holmes cm: malignant transformation of a site of prior diabetic foot ulceration to verrucous carcinoma: a case report. wounds: a compendium of clinical research and practice 29: e125, 2017. 15. nakamura y, kashiwagi k, nakamura a, et al.: verrucous carcinoma of the foot diagnosed using p53 and ki-67 immunostaining in a patient with diabetic neuropathy. the american journal of dermatopathology 37: 257, 2015. 16. penera ke, manji ka, craig ab, et al.: atypical presentation of verrucous carcinoma: a case study and review of the literature. foot & ankle specialist 6: 318, 2013. efficacy and safety of tralokinumab with concomitant topical corticosteroids in north american adults with moderate-to-severe atopic dermatitis: a subanalysis of the ecztra 3 trial boni e. elewski,1 matthew j. zirwas,2 richard g. langley,3 andrew f. alexis,4 karen a. veverka,5 john zoidis,5 azra kurbasic,6 jonathan i. silverberg7 1university of alabama, birmingham, al, usa; 2probity medical research, columbus, oh, usa; 3dalhousie university, halifax, nova scotia, canada; 4icahn school of medicine at mount sinai, new york, ny, usa; 5leo pharma, madison, nj, usa; 6leo pharma a/s, ballerup, denmark; 7the george washington university school of medicine and health sciences, washington, dc, usa leo 6 fall clinical dermatology conference, las vegas, nv, usa, october 29−november 1, 2020 introduction • atopic dermatitis (ad) is a common, chronic inflammatory skin disease, characterized by excessive pruritus and sleep disturbance, among other symptoms1-3 • tralokinumab is a fully human monoclonal antibody that specifically neutralizes interleukin-13 (il-13), a key cytokine of the chronic type 2 inflammation underlying ad; il-13 is overexpressed in lesional and non-lesional ad skin4-6 • ecztra 3 (nct03363854) was a phase 3, randomized, double-blind, placebocontrolled trial that evaluated the efficacy and safety of subcutaneous tralokinumab 300 mg every 2 weeks (q2w) vs. placebo (after a loading dose of 600 mg), in combination with topical corticosteroids (tcs) as needed, for an initial treatment period of 16 weeks in adults with moderate-to-severe ad across europe and north america — significantly more patients achieved the primary endpoints of investigator’s global assessment (iga) score of 0/1 (clear/almost clear) and/or a 75% improvement in eczema area and severity index (easi-75) at week 16 with tralokinumab plus tcs compared with placebo plus tcs — tralokinumab demonstrated improvements vs. placebo across key secondary endpoints in patient-reported outcomes (dermatology life quality index [dlqi], pruritus numeric rating scale [nrs], and scoring atopic dermatitis [scorad]) at week 16 — cumulative tcs use in tralokinumab-treated patients was lower than that of those who received placebo at week 16, suggesting achievement of endpoints was not likely attributable to tcs use alone objective • to evaluate the efficacy and safety of tralokinumab 300 mg q2w in combination with tcs in the ecztra 3 north american subpopulation at week 16 methods study design and patients • ecztra 3 was a randomized, double-blind, placebo-controlled, 32-week trial in adult patients with moderate-to-severe ad (figure 1) • patients were enrolled from europe (belgium, germany, the netherlands, poland, spain, and uk) and north america (usa and canada) • eligible patients were 18 years of age, with a confirmed diagnosis of ad for 1 year and ad involvement of 10% of body surface area, easi score of 12 at screening and 16 at baseline, iga score of 3, pruritus nrs score of 4, and were candidates for systemic therapy due to a recent (within 1 year) history of inadequate response or intolerance to topical treatment • patients were stratified by region and baseline disease severity (iga-3 [moderate] or iga-4 [severe]) and were randomized 2:1 to receive subcutaneous tralokinumab 300 mg or placebo q2w (after a loading dose of 600 mg), plus tcs as needed, for an initial treatment period of 16 weeks • use of tcs (mometasone furoate: us class 4 [midstrength]) was permitted as early as day 0, after a washout period of 2 weeks for tcs • rescue treatment, which included higher-potency tcs (e.g. clobetasol), was permitted in the form of topical and systemic medications to control intolerable ad symptoms endpoints • primary endpoints were defined as iga-0/1 and/or easi-75 at week 16 • key secondary endpoints included reduction of worst daily pruritus nrs (weekly average) of at least 4 from baseline to week 16 and change from baseline to week 16 in scorad and dlqi safety assessments • adverse events were collected from the first trial-related activity after patients provided informed consent until completion of the clinical trial statistical analysis • for binary endpoints, the difference in response rates between treatment groups was analyzed using the cochran-mantel-haenszel test, stratified by baseline iga score; patients receiving rescue medication prior to week 16 or with missing data were considered non-responders • continuous endpoints were assessed using a mixed-effect model for repeated measurements, with an unstructured covariance matrix to model within-patient variation and the mean change modeled as: change from baseline = treatment*week + baseline*week + baseline iga; denominator degrees of freedom were estimated using kenward-roger approximation — data collected after permanent discontinuation of investigational medicinal product or after initiation of rescue medication were excluded from the analysis • descriptive statistics were used to present baseline demographics, baseline disease characteristics, and safety assessments results patient characteristics • in total, 380 patients were randomized in ecztra 3, with 160 patients (42.1%) from north america (table 1) • overall, the north american and primary study populations had similar baseline demographics, although there was slight variation in the baseline disease characteristics:7 — the percentage of severe ad (iga-4) was slightly lower in the north american population, although mean easi scores did not objectively differ — mean body surface area involvement with ad was slightly lower in the north american population iga and easi-75 at week 16 • at week 16, a numerically higher proportion of tralokinumab-treated patients in the north american population achieved iga-0/1 compared with placebo (40.0% vs. 25.9%) [figure 2] • a higher proportion of tralokinumab-treated patients in the north american population achieved easi-75, compared with placebo (58.1% vs. 37.0%) at week 16 use of rescue medication • use of rescue medication, which included higher-potency tcs or systemic treatment for ad, was low in the north american population during the initial treatment period (figure 3) — when compared with placebo, rescue medication use was lower in tralokinumabtreated patients (4.7% vs. 9.3%) change in scorad, dlqi, and pruritus nrs • reduction in scorad (−38.6 vs. −23.0) and dlqi (−11.5 vs. −7.6) were greater with tralokinumab compared with placebo in the north american population from baseline to week 16 (figure 4) • a numerically greater proportion of the north american population treated with tralokinumab achieved a worst daily pruritus nrs reduction of 4 at week 16 compared with placebo (42.3% vs. 31.5%) [figure 5] safety • the overall rate of adverse events was similar between tralokinumab and placebo groups in the north american population (table 2) • most adverse events were mild to moderate in severity figure 1. ecztra 3 trial design placebo q2w + tcs tralokinumab q2w + tcs tralokinumab q4w + tcs (n=69) tralokinumab q2w + tcs (n=69) screening continuation treatment clinical response defined as iga-0/1 or easi-75 o�-treatment period safety follow-up 0 32 weeks 46weeks16 weeks-6 weeks n=253 this ecztra 3 sub-analysis focused on the initial treatment period n=127 2:1 randomization 1:1 re-randomization washout of tcs and other ad medication initial treatment 300 mg q2w after initial loading dose (600 mg) 16-week responders 16-week non-responders 16-week responders primary endpoints • iga-0/1 and/or easi-75 at week 16 secondary endpoints • change in scorad from baseline to week 16 • change in dlqi score from baseline to week 16 • reduction of worst daily pruritus nrs (weekly average) �4 from baseline to week 16 • adverse events/serious adverse events by preferred term 16-week non-responders tralokinumab q2w + tcs (n=95) placebo q2w + tcs (n=41) tralokinumab q2w + tcs (n=79) figure 3. rescue medication use in the ecztra 3 north american population during the initial 16-week treatment period p a ti e n ts , % 12 8 10 6 4 2 0 9.3% 4.7% tralokinumab q2w + tcs (n=104) placebo + tcs (n=54) treatment figure 4. change in (a) scorad and (b) dlqi in the ecztra 3 north american population at week 16 c h a n g e in s c o r a d a 0 −50 −40 −30 −20 −10 c h a n g e in d lq i b 0 −14 −8 −6 −12 −10 −4 −2 −38.6 *** −11.5 *** −7.6 −23.0 tralokinumab q2w + tcs (n=105) placebo + tcs (n=54) treatmenttreatment tralokinumab q2w + tcs (n=105) placebo + tcs (n=54) ***p0.001 vs. placebo + tcs. data collected after permanent discontinuation of investigational medicinal product or initiation of rescue medication not included. repeated measurements model: change from baseline = treatment*week + baseline*week + baseline iga. figure 5. proportion of patients achieving a reduction in pruritus nrs 4 in the ecztra 3 north american population at week 16 p a ti e n ts , % 50 40 30 20 10 0 31.5% 42.3% tralokinumab q2w + tcs (n=104) placebo + tcs (n=54) treatment patients receiving rescue medication prior to week 16 or with missing data were considered non-responders. figure 2. (a) iga-0/1 and (b) easi-75 in the ecztra 3 north american population at week 16 p a ti e n ts , % a 0 p a ti e n ts , % b 70 30 20 10 0 40 50 60 70 30 20 10 40 50 60 25.9% 40.0% tralokinumab q2w + tcs (n=105) placebo + tcs (n=54) tralokinumab q2w + tcs (n=105) placebo + tcs (n=54) treatmenttreatment 37.0% 58.1% * *p0.05 vs. placebo + tcs. patients receiving rescue medication prior to week 16 or with missing data were considered non-responders. table 1. patient demographics and disease characteristics at baseline north america (n=160) tralokinumab q2w + tcs (n=106) placebo + tcs (n=54) mean age (sd) 42.4 (17.6) 39.5 (16.2) male, % 46.2 53.7 mean duration of ad, years (sd) 27.1 (18.3) 27.7 (15.7) iga score of 4, % 37.1 38.9 mean easi score (sd) 26.2 (11.4) 28.3 (11.4) mean scorad (sd) 65.2 (13.4) 67.5 (13.2) mean dlqi (sd) 16.5 (7.3) 18.0 (7.1) mean weekly average worst daily pruritus nrs score (sd) 7.7 (1.6) 8.2 (1.6) mean bsa involvement with ad, % (sd) 41.0 (20.6) 41.2 (23.6) bsa, body surface area; sd, standard deviation. table 2. adverse events in the initial 16-week treatment period n (%) north america (n=160) tralokinumab q2w + tcs (n=105) placebo + tcs (n=54) at least one adverse event 60 (57.1) 28 (51.9) at least one serious adverse event 0 1 (1.9) adverse event leading to withdrawal from trial 2 (1.9) 0 severity mild moderate severe 50 (47.6) 18 (17.1) 0 20 (37.0) 12 (22.2) 3 (5.6) outcome not recovered/not resolved recovering/resolving recovered/resolved recovered/resolved with sequelae 18 (17.1) 2 (1.9) 55 (52.4) 1 (1.0) 5 (9.3) 2 (3.7) 25 (46.3) n/a n/a, not available. references 1. weidinger s, novak n. lancet 2016; 387: 1109–1122. 2. silverberg ji et al. ann allergy asthma immunol 2018; 121: 340–347. 3. dalgard fj et al. j invest dermatol 2015; 135: 984–991. 4. bieber t. allergy 2020; 75: 54–62. 5. tsoi lc et al. j invest dermatol 2019; 139: 1480–1489. 6. popovic b et al. j mol biol 2017; 429: 208–219. 7. silverberg ji et al. br j dermatol 2020; in press. disclosures • boni e. elewski has received honoraria as a consultant from boehringer ingelheim, bristol-myers squibb, celgene, leo pharma, lilly, menlo therapeutics, novartis, pfizer, sun, valeant (ortho dermatologics), and verrica and received research funding from abbvie, anaptysbio, boehringer ingelheim, bristol-myers squibb, celgene, incyte, leo pharma, lilly, menlo therapeutics, merck, novartis, pfizer, regeneron, sun, valeant (ortho dermatologics), and vand • matthew j. zirwas has acted as a consultant for abbvie, aclaris, arcutis, asana, aseptic md, avillion, ds biopharma, fitbit, foamix, genentech, incyte, janssen, leo pharma, lilly, l’oreal, menlo, novartis, ortho dermatologics, pfizer, regeneron, sanofi, and ucb • richard g. langley has received honoraria as an advisory board member from abbvie, amgen, boehringer ingelheim, celgene, leo pharma, lilly, merck, novartis, pfizer, and ucb, and as a speaker from abbvie, amgen, celgene, leo pharma, merck, novartis, and pfizer • andrew f. alexis has acted as a consultant for beiersdorf, bristol-myers squibb, celgene, dermavant, foamix, galderma, leo pharma, l’oreal, menlo therapeutics, novartis, pfizer, sanofi/regeneron, scientis, ucb, unilever, and valeant (bausch health) and received grants/research support from almirall, bristol-myers squibb, cara, celgene, galderma, leo pharma, menlo therapeutics, novartis, and valeant (bausch health) • karen a. veverka, john zoidis, and azra kurbasic are employees of leo pharma • jonathan i. silverberg has received honoraria as a consultant/advisory board member from leo pharma and acted as a consultant for, and/or received grants/honoraria from, abbvie, anaptysbio, asana biosciences, galderma research and development, glaxosmithkline, glenmark generics, kiniksa, leo pharma, lilly, medimmune, menlo therapeutics, pfizer, puricore, regeneron, and sanofi acknowledgments • the ecztra 3 study was sponsored by leo pharma • medical writing and editorial assistance were provided by henna potigadoo, msc, and lauren smith, ba (hons), from mccann health, funded by leo pharma • the north american population represented 42.1% of the overall ecztra 3 study population • in this subanalysis of the ecztra 3 trial, tralokinumab 300 mg q2w plus tcs was well tolerated and displayed superior efficacy in patients with moderateto-severe ad in the north american population compared with placebo — tralokinumab plus tcs demonstrated improvements in ad symptoms and patient quality of life • tralokinumab plus tcs was well tolerated in the north american population, suggesting no special considerations in safety for this trial subpopulation are required • overall, tralokinumab plus tcs displayed similar efficacy and safety across the north american population comparable to that of the primary study population7 conclusions acknowledgements: medical writing support was provided by prescott medical communications group (chicago, il) with financial support from ortho dermatologics; ortho dermatologics is a division of bausch health us, llc • presented at winter clinical dermatology conference 2023 • january 13-18, 2023 • waimea, hi efinaconazole in the age of antifungal resistance ahmed gamal,1 mohammed elshaer,1,2 lisa long,1 thomas s. mccormick,1 boni elewski,3 mahmoud a. ghannoum1,4 1case western reserve university, cleveland, oh; 2mansoura faculty of medicine, mansoura, egypt; 3university of birmingham, al; 4university hospitals cleveland medical center, cleveland, oh.*bausch health us, llc is an affiliate of bausch health companies inc. background � the global rise and spread of antifungal resistance is complicating the treatment of onychomycosis, a fungal infection of the toenail bed or plate � causative dermatophyte species resistant to oral antifungals like terbinafine are being increasingly detected1,2 � further, resistant yeast and mold species are now categorized by the world health organization as fungal pathogens that represent a great threat to public health3 � accordingly, patients in the us are presenting with onychomycosis resistant to terbinafine or second-line systemic therapies like oral fluconazole or itraconazole4 � it is crucial to find alternative approaches to combat this clinical resistance, including implementing antifungal stewardships programs and identifying antifungals that are effective against both susceptible and resistant fungal strains objective � the goal of this study was to evaluate the activity of oral and topical antifungals against susceptible and resistant clinical isolates of dermatophytes, yeasts, and molds methods � antifungal activity of efinaconazole was compared with terbinafine, itraconazole, and fluconazole using in vitro assays evaluating minimum inhibitory concentration (mic) and minimum fungicidal concentration (mfc) against susceptible and resistant strains � mic is the lowest concentration of an antifungal that inhibits fungal growth (threshold for inhibition varies depending upon fungus being tested); mic50 is the lowest concentration that inhibits growth in 50% of the fungal isolates tested • mic testing was performed according to the clinical and laboratory standard institute (clsi) microdilution methods for yeasts5 and for dermatophytes and non-dermatophyte molds6 � mfc determines if a test compound is fungicidal (≥99.9% reduction of the fungus) or fungistatic � lower mic and mfc values are more favorable, as less drug is required for antifungal activity � clinical isolates tested due to suspicion of antifungal resistance included: • dermatophytes (trichophyton mentagrophytes [n=16], t. rubrum [n=43], t. tonsurans [n=18], and t. violaceum [n=4]) • yeasts (candida albicans [n=55] and c. auris [n=30]) • molds (fusarium sp., scedosporium sp., and scopulariopsis sp. [n=15 each]) results � efinaconazole showed superior potent activity against a broad panel of susceptible and resistant dermatophyte, candida, and mold isolates (figures 1–3) � although none of the tested compounds showed fungicidal activity against all tested isolates, efinaconazole demonstrated more fungicidal activity against t. rubrum isolates compared to other antifungals (data not shown) figure 3. antifungal ac tivity against molds 100 10 1 0.010.1 drug concentration (µg/ml) on logarithmic scale fluconazole (2 – >64) terbina�ne (0.5 – >64) itraconazole (1 – >64) e�naconazole (0.016 – 2) more potent antifungal activity all mold isolatesa (n=45) e�naconazole was the most active compound against different types of molds, including those with high itraconazole and terbina�ne mics ascedosporium, fusarium spp., scopulariopsis. bar graphs indicate mic ranges for all isolates tested; range values indicated below drug name. conclusions � efinaconazole demonstrated superior in vitro activity compared to fluconazole, itraconazole, and terbinafine against a broad range of dermatophytes and non-dermatophytes commonly implicated in onychomycosis � efinaconazole also demonstrated potent antifungal activity against isolates resistant to terbinafine and/or itraconazole, suggesting efinaconazole may be an efficacious treatment for resistant organisms references 1. hiruma j, et al. j dermatol. 2021;48(4):564-567. 2. noguchi h, et al. j dermatol. 2019;46(12):e446-e447. 3. world health organization. who releases first-ever list of health-threatening fungi. accessed november 29, 2022. https://www.who.int/news/item/25-102022-who-releases-first-ever-list-of-healththreatening-fungi. 4. gu d, et al. jaad case rep. 2020;6(11):1153-1155. 5. clinical and laboratory standards institute. 2017. document m27ed4e. 6. clinical and laboratory standards institute. 2017. document m38ed3e. author disclosures boni elewski has provided clinical research support (research funding to university) for abbvie, anaptys-bio, boehringer ingelheim, bristol-myers squibb, celgene, incyte, leo pharma, lilly, merck, menlo, novartis, pfizer, regeneron, sun pharma, ortho dermatologics, and vanda; and as consultant (received honorarium) from boehringer ingelheim, bristol meyers squibb, celgene, leo pharma, lilly, menlo, novartis, pfizer, sun pharma, ortho dermatologics, and verrica. mahmoud ghannoum has acted as a consultant or received contracts from scynexis, inc, bausch & lomb, pfizer, and mycovia. the remaining authors have nothing to disclose. figure 1. antifungal ac tivity against dermatophy tes e�naconazole demonstrated the most potent antifungal activity against 81 dermatophyte isolates, including 27 resistant isolates with elevated mics against terbina�ne 100 10 1 0.1 0.0010.01 drug concentration (µg/ml) on logarithmic scale mic 50 = 1 fluconazole(≤0.125 – >64) mic 50 = 0.03 terbina�ne(≤0.001 – >64) mic 50 = 0.03 itraconazole(≤0.016 – 1) mic 50 = 0.002 e�naconazole(≤0.001 – 0.25) more potent antifungal activity all dermatophyte isolates (n=81) 100 10 1 0.1 0.0010.01 drug concentration (µg/ml) on logarithmic scale mic 50 = 0.5 fluconazole(≤0.125 – 32) mic 50 = 4 terbina�ne(0.5 – >64) mic 50 = 0.03 itraconazole(≤0.016 – 0.5) mic 50 = 0.002 e�naconazole(≤0.001 – 0.25) more potent antifungal activity resistant dermatophyte isolatesa (n=27) aresistant dermatophytes defined as isolates that showed elevated mic values against terbinafine. bar graphs indicate mic ranges for all isolates tested; range values indicated below drug name. diamonds indicate mic50, defined as lowest concentration of antifungal that inhibits growth in 50% of the isolates tested. figure 2. antifungal ac tivity against candida 0.001100 10 1 0.1 0.00010.01 drug concentration (µg/ml) on logarithmic scale mic 50 = 1 fluconazole(≤0.125 – >64) mic 50 = 2 terbina�ne(≤0.125 – >64) mic 50 = 0.25 itraconazole(≤0.03 – >64) mic 50 = 0.016 e�naconazole(≤0.00024 – 32) more potent antifungal activity 100 10 1 0.1 0.0010.01 drug concentration (µg/ml) on logarithmic scale terbina�ne (16 – >64) itraconazole (1 – >64) e�naconazole (0.008 – 32) more potent antifungal activity all isolates (n=85)candida resistant isolatesa (n=11)candida e�naconazole demonstrated the most potent antifungal activity against 85 isolates, including 11 isolates with high itraconazole and/or terbina�ne micscandida aresistant candida: four c. albicans isolates with elevated mics against terbinafine, four isolates (c. albicans and c. auris) with elevated mics against itraconazole, and three c. albicans isolates with elevated mics against both terbinafine and itraconazole. bar graphs indicate mic ranges for all isolates tested; range values indicated below drug name. diamonds indicate mic50, defined as lowest concentration of antifungal that inhibits growth in 50% of the isolates tested. skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 437 compelling comments diaries of james clarke white tyler marion, bs, mba1, jake alan gibbons, bsa1 1the university of texas medical branch school of medicine, galveston, tx james clarke white, born in 1833 of scotchirish descent, was a true pioneer for the specialty of dermatology. growing up in maine, his innate sense of curiosity drove him to pursue many scholastic endeavors. his early thirst for knowledge was genuine and without intention; he studied for the knowledge itself. he learned botany and ornithology, and often shot and stuffed birds for the harvard natural history society as an undergraduate.1 in his senior year of college, he chose medicine, writing in his diary: “there came to me this afternoon in church the sudden conviction that i would choose medicine as my life work.”2 white earned his m.d. from harvard medical school. in 1855, he served as medical house pupil at massachusetts general hospital, and later traveled to vienna to continue his medical studies.2 in vienna, white became interested in skin pathology. there, he focused on dermatology without any plan of making it his sole focus. much of his passion for dermatology can be attributed to ferdinand von hebra, chief of the german school of dermatology, who captivated white with his teaching methods and detailed clinical illustrations.2 upon return to massachusetts, white worked as a professor and developed the resolution to specialize specifically in dermatology, a rare decision in the medical landscape at that time. he was appointed as the first chair of dermatology at harvard, a position specifically designed for him. white went on to become a founding member and first president of the american dermatological association.1 additionally, white contributed to medical literature by publishing his own book entitled dermatitis venenata.2 in 1914, white privately published sketches of my life, a diary of personal reflections from his times at harvard.1 dr. white was a figurehead of dermatology and served a critical role in its development as a unique medical specialty. figure 1. photograph of james clarke white. skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 438 conflict of interest disclosures: none. funding: none. corresponding author: tyler marion, bs, mba the university of texas medical branch 301 university blvd, galveston, tx email: trmarion9@gmail.com references: 1. shattuck, f. (1917). james clarke white (1833-1916). proceedings of the american academy of arts and sciences,52(13), 873876. retrieved from http://www.jstor.org/stable/20025731 2. post a. james clarke white, m.d. the boston medical and surgical journal. 1916;174(3):106-106. doi:10.1056/nejm191601201740318. mailto:trmarion9@gmail.com http://www.jstor.org/stable/20025731 http://www.jstor.org/stable/20025731 maximal use study of tapinarof cream 1% in subjects with extensive plaque psoriasis john e jett,1 michael mclaughlin,1 mark s lee,2 lawrence charles parish,3 glenn tabolt,1 timothy wilson,1 matthew c somerville,1 wayne dellamaestra,1 stephen c piscitelli1 1dermavant sciences, inc., durham, nc, usa; 2progressive clinical research, san antonio, tx, usa; 3paddington testing company, inc., philadelphia, pa, usa synopsis ■ psoriasis is a chronic, immune-mediated disease characterized by scaly, erythematous, and pruritic plaques that can be painful and disfiguring1 ■ there is a need for efficacious topical therapies for plaque psoriasis without concerns for duration of treatment due to potential for long-term adverse effects or local intolerance. however, no topicals with novel mechanisms have been introduced in recent years ■ tapinarof is a novel, first-in-class, non-steroidal, topical therapeutic aryl hydrocarbon receptor modulating agent (tama) in clinical development for the treatment of psoriasis and atopic dermatitis ■ this phase 2a, multicenter, open-label study was designed to assess the safety and tolerability, pharmacokinetics (pk), and efficacy of tapinarof cream 1% once daily (qd) under maximal use conditions for 29 days in adults with plaque psoriasis and a body surface area (bsa) involvement of ≥20% objectives ■ the primary objectives were to evaluate the safety and tolerability, and pk of topical tapinarof cream 1% in adult patients with extensive plaque psoriasis ■ the secondary objectives were to exclude clinically relevant effects on qt interval corrected for heart rate using fridericia’s formula (qtcf) and evaluate the efficacy of tapinarof cream 1% in adult patients with extensive plaque psoriasis methods ■ in this phase 2a, multicenter, open-label study, patients with extensive plaque psoriasis received tapinarof cream 1% qd for 29 days (figure 1) ■ key inclusion and exclusion criteria are presented in table 1 figure 1. study design adult patients with plaque psoriasis • aged 18–75 years • pga score ≥3 • bsa ≥20% (n=21) open-label treatment (29 days) tapinarof cream 1% qd (n=19) day 29 final assessments follow-up visit 7 days after end of treatment bsa, body surface area; pga, physician global assessment; qd, once daily. endpoints and statistical analysis ■ safety and tolerability were evaluated by assessment of clinical laboratory tests, physical examinations, vital signs, electrocardiogram (ecg), and local tolerability scales ■ plasma pk parameter estimates for tapinarof and its metabolite, tapinarof sulfate, on days 1 and 29 were calculated using non-compartmental analysis of the plasma concentration versus time data, as data permitted. assay lower limits of quantitation were 50 pg/ml for tapinarof and 10 pg/ml for tapinarof sulfate ■ to exclude effects of tapinarof cream 1% on qtcf, change in qtcf at each time point after application and by tapinarof plasma concentration were analyzed based on linear mixed-effects models as previously described.2 qt prolongation was assessed per the food and drug administration (fda) requirements for all investigational drugs ■ mean and percent change in physician global assessment (pga), psoriasis area and severity index (pasi), and bsa from baseline to day 29 were summarized descriptively and analyzed with a one-sample t-test. treatment success, defined as the proportion of patients with a pga score of clear (0) or almost clear (1) and ≥2-grade improvement in pga score from baseline, was assessed table 1. key inclusion and exclusion criteria key inclusion criteria males and females aged 18–75 years confirmed chronic psoriasis and stable disease for ≥6 months bsa involvement ≥20% pga score ≥3 at screening key exclusion criteria psoriasis other than plaque variant infection of any of the psoriatic plaques evidence of significant concurrent diseases that would affect participation or interpretation of results laboratory values significantly outside normal ranges or qtcf interval >470 milliseconds concomitant use of medications or ultraviolet light therapy that could affect efficacy assessments bsa, body surface area; pga, physician global assessment; qtcf, qt interval corrected for heart rate using fridericia’s formula. results study population ■ in total, 21 patients (of 36 screened) were enrolled into the study and received tapinarof cream 1% qd; 19 patients (90.5%) completed the study, one patient (4.8%) withdrew consent, and one patient (4.8%) was lost to follow-up ■ patient demographics and baseline disease characteristics are presented in table 2 table 2. baseline patient demographics and characteristics baseline demographics and characteristics tapinarof 1% qd (n=21) age, years, mean (sd) 51.8 (13.9) male, n (%) 13 (61.9) female, n (%) 8 (38.1) childbearing potential = yes 2 (25.0) ethnicity, n (%) hispanic or latino 9 (42.9) not hispanic or latino 12 (57.1) race, n (%) american indian or alaska native 1 (4.8) black or african american 3 (14.3) white 16 (76.2) not reported 1 (4.8) pga of 3 – moderate, n (%) 13 (61.9) pga of 4 – severe, n (%) 8 (38.1) %bsa affected, mean (sd) 27.2 (7.5) %bsa affected, median (min, max) 25.5 (20.5, 46.0) pasi, mean (sd) 24.7 (7.1) pasi, median (min, max) 22.2 (14.4, 36.9) bsa, body surface area; pasi, psoriasis area and severity index; pga, physician global assessment; sd, standard deviation.ts safety and cardiodynamic results ■ tapinarof was well tolerated at application sites, including in seven patients (33.3%) who applied tapinarof to sensitive areas, such as genitals, face, neck, and skin folds ■ there were no treatment interruptions and no patient discontinued study drug due to treatment-emergent adverse events (teaes) ■ twelve patients (57.1%) reported teaes; the most frequently reported teaes related to the study drug were folliculitis (n=4) and headache (n=2) ■ there were no clinically meaningful changes in clinical laboratory values, vital signs, qtc interval, or other ecg parameter values ■ cardiodynamic analysis by time point (figure 2a) and by concentration–qt modeling (figure 2b) demonstrated tapinarof had no clinically relevant effects on qtcf following application and at plasma concentrations up to ~4600 pg/ml. a qtcf effect exceeding 10 milliseconds can be excluded within the range of tapinarof plasma concentrations up to ~4600 pg/ml figure 2. change from baseline qtcf by time point (a) and qtcf by concentration–qt modeling (b) error bars represent 90% ci. dotted horizontal line represents qtcf effect exceeding 10 milliseconds. ci, confidence interval; qtcf, qt interval corrected for heart rate using fridericia’s formula. pk results ■ tapinarof plasma exposure was low, with 68% of samples below the lower limit of quantitation (50 pg/ml) ■ the highest tapinarof plasma concentrations were observed on day 1 (figure 3a), which were approximately 10-fold lower by day 29 (figure 3b) ■ no patient had measurable concentrations of tapinarof sulfate at any time point figure 3. mean (sd) tapinarof plasma concentration versus time curves on days 1 (a) and 29 (b) *all tapinarof sulfate concentrations were below the lloq of 10 pg/ml. tapinarof lloq was 50 pg/ml. lloq, lower limit of quantitation. sd, standard deviation. efficacy results ■ nineteen patients who completed the study were included in the efficacy analysis (table 3) ■ mean (standard deviation) change in pga score from baseline at day 29 was –1.2 (1.03) (p<0.0001) ■ at day 29, 14 patients (73.7%) had ≥1-grade improvement in pga score, six patients (31.6%) had ≥2-grade improvement, and four patients (21.1%) achieved pga score of 0 or 1 and ≥2-point improvement in pga score ■ at day 29, 18 patients (95%) demonstrated improvement in pasi and 17 patients (89%) demonstrated improvement in bsa during the study ■ mean percent change in pasi score from baseline at day 29 was –59.6% (p<0.0001) ■ mean percent change in bsa from baseline at day 29 was –49.8% (p<0.0001) table 3. efficacy following 29 days of treatment efficacy parameter tapinarof 1% qd (n=19) patients with ≥1-point improvement in pga score, n (%) 14 (73.7) patients with ≥2-point improvement in pga score, n (%) 6 (31.6) patients with pga score of 0 or 1 and ≥2-point improvement in pga score, n (%) 4 (21.1) mean change in pga from baseline to day 29 (sd) –1.2 (1.0) mean % change in pasi score from baseline to day 29 (sd) –59.6 (29.0) mean % change in bsa from baseline to day 29 (sd) –49.8 (32.5) patients who achieved pasi75, n (%) 7 (36.8) bsa, body surface area; pasi, psoriasis area and severity index; pasi75, ≥75% improvement in pasi from baseline; pga, physician global assessment; qd, once daily; sd, standard deviation. conclusions ■ tapinarof cream 1% has a favorable safety profile and is well tolerated, including in sensitive areas, with no clinically meaningful effect on qtc interval or other ecg parameters per fda requirements for all investigational drugs ■ application of tapinarof cream 1% qd resulted in limited systemic exposure, even in subjects with extensive plaque psoriasis up to 46% bsa ■ tapinarof cream 1% qd demonstrated significant efficacy after only 4 weeks of treatment in subjects with moderate to severe plaque psoriasis ■ these findings support the safety and efficacy of tapinarof demonstrated in other clinical studies,3,4 including the pivotal phase 3 trials psoaring 1 and psoaring 2 ■ tapinarof cream may address many of the limitations of each of the current therapeutic classes for psoriasis, with the potential to be used across the disease spectrum, providing physicians and patients with a highly effective treatment option references 1. menter a, et al. j am acad dermatol. 2008;58:826–850; 2. garnett c, et al. j pharmacokinet pharmacodyn. 2018;45:383–397; 3. robbins k, et al. j am acad dermatol. 2019;80:714–721; 4. stein gold l, et al. j am acad dermatol. 2020; doi: 10.1016/j.jaad.2020.04.181 acknowledgments this study was funded by dermavant sciences, inc. the authors thank the participating investigators, patients and their families, and colleagues involved in the conduct of the study. editorial support under the guidance of the authors was provided by apothecom, uk, and was funded by dermavant sciences, inc. in accordance with good publication practice (gpp3) guidelines (ann intern med. 2015;163:461–464). contact dr stephen c piscitelli at steve.piscitelli@dermavant.com with questions or comments. δ q t cf ( m il li se co n d s) day 1 time point (hours) a 15 10 5 0 tapinarof cream 1% 10 milliseconds -5 -10 -15 1 2 3 4 5 8 12 24 δ q t cf ( m il li se co n d s) tapinarof concentration (pg/ml) b 40 20 0 tapinarof cream 1% mean predicted 90% ci 10 milliseconds -20 0 -40 1000 2000 3000 4000 m e a n c o n ce n tr a ti o n ( p g /m l ) nominal time (hours) a b day 1 day 29 10000 1000 100 10 1 tapinarof cream 1% 1 10000 1000 100 10 1 0 2 3 4 5 8 12 24 tapinarof sulfate* m e a n c o n ce n tr a ti o n ( p g /m l ) nominal time (hours) 0 1 2 3 4 5 8 12 24 low rate of keloid recurrences following treatment of keloidectomy sites with a biological effective dose 30 of superficial radiation brian berman, m.d., ph.d mark s. nestor, m.d., ph.d joshua fox, m.d. michael jones, m.d. george schmieder, d.o. eduardo t. weiss, m.d. purpose design recurrences of keloids at sites of previously excised keloids is a well-recognized common occurrence following keloidectomy, and based on review of the published literature, has been reported to occur approximately in 71% of cases. superficial radiation therapy (srt) reduces wound fibroblast proliferation and enhances apoptosis. in this multicenter, case series report the recurrence rate of keloids post keloidectomy with perioperative treatment with a biological effective dose 30 of superficial radiation was determined. 132 keloids in 104 patients were surgically excised. on postoperative day 1 the suture closure line with a 5 mm margin received a biologically effective dose 30 (bed 30), either 70 kv or 100 kv, of superficial radiation. one of the 3 following superficial radiation bed 30 fractionation protocols was employed post keloidectomy: one fraction of 13 gy on postoperative day 1; or 2 fractions of 8 gy on postoperative days 1 and 2; or 3 fractions of 6 gy on postoperative days 1, 2 and 3. keloidectomies and superficial radiation therapy (srt) treatments were performed at one of 5 facilities from november 2013-january 2017. results the 132 srt-treated keloidectomy sites were in 6 anatomical sites: ear (40), head/neck (23), arm/shoulder (17), back/ buttocks (9), chest/abdomen (34), and scalp (9). the follow-up period ranged from 3 months to 3 years, with the majority (83/104) have been followed for more than 1 year. two (1.9%) keloids recurred at excision sites. one recurrence occurred in a patient who had received a single fraction of 13 gy. the second recurrence occurred in a woman following excision of her chest keloid and srt treatment, and wound dehiscence 10 days postoperatively and subsequently let to heal by secondary intent. hyperpigmentation in the irradiated field was the most common adverse event, noted in a minority of patients and which tended to resolve after several months posttreatment. left earlobe keloid. pre-excision post-excision srt 6 gy on pod 1, 2, 3 suture removal at pod 7 conclusion the observed 1.9% rate of keloid recurrence following keloidectomy and excision site treatment with superficial radiation therapy (bed 30) is markedly lower than that reported in the literature following keloid excision alone. sensushealthcare.com 1-800-324-9890 fc17postersensusberman.pdf skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 22 rising derm stars ® abstracts increased pd-l1 tumor expression correlates with high rate of response to pd-1 inhibitors in patients with unresectable, recurrent, and metastatic cutaneous squamous cell carcinoma nathan bowers, md1, mercedes porosnicu, md2 1department of dermatology, wake forest university school of medical, winston-salem, nc 2department of internal medicine, section of hematology & oncology, wake forest university school of medicine, winston salem, nc pd-1 inhibitors were approved for locally advanced and metastatic cutaneous squamous cell carcinoma (cscc) in 2019 with orr of 47% and cr of 4%. the identification of tumor characteristics that predict potential responders to immune checkpoint inhibitors (ici) is an area of ongoing research. here we present a series of consecutive patients with locally advanced unresectable, recurrent, or metastatic cscc treated with pd-1 inhibitors and analyze tumor and blood genomics as well as pd-l1 expression with the aim to correlate with treatment response. we analyzed all cases of cscc treated with single agent pd-1 inhibitors in the last 2 years at wake forest comprehensive cancer center. demographic and outcome data was collected. tumors tested for genomics and pd-l1 expression in all cases with available tissue. pd-l1 tumor expression was tested by ihc utilizing dako 22c3 pharmdx antibodies. tumor genomic studies including tmb and msi were performed by foundation medicine platform. blood was tested for circulating tumor dna by guardant 360 platform, at the beginning of treatment and in follow up at the time of maximum response. response was assessed by recist 1.1 criteria. eleven patients with cscc treated with pd1 ici were included in this study. five patients had locally advanced disease, five patients had recurrent locally advanced disease, and three patients had metastatic disease. three patients received treatment for at least 12 months and all have cr to date. two patients have been on treatment for 6 months, and they have excellent pr with possible cr per imaging studies. of the six patients who have been on treatment for less than 6 months, one patient has excellent pr with negative pet, three patients have very good clinical response with imaging studies pending, one patient has questionable response, and one patient only recently started treatment. treatment is well tolerated with no treatment discontinuation. immune-related complications are rare consisting of only one patient developing hypothyroidism during introduction methods results skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 23 table 1. g a s l/r/m iod (mo) ior d previous pd-l1 tmb guardant before io guardant after io f1 ae obs tp53 other tp53 other tp53 other m 73 n l 20 cr on surg, adj crt tps 60% 61 0 0 y163n arid1a atm g266e r248q brip1, cd22, fancc, men1, notch2 other primary cscc x5 ra-pdn 5 mg + mtx f 97 n l 14 cr 3 mo tps 60% 11 0 kit crca1 0 kit brca2 e286k cdkn2a, notch2, tert hypothyroid other primary cscc x3 m 76 n l 14 cr on surg, adj rt tps 30% 19 0 jak2 0 0 p278s asxl, cdkn2a, notch1, pik3ca, tert fatigue mets to right parotid f 81 n l 9 pr on n/a net s99f q100 q16 ss snv cdkn2a brca2 map2k1 nd nd net net other primary cscc x2 m 91 fs m 6 pr on adj rt net net net net net net net net fatigue m 75 n r 4 pr on none tps 20% 21 h193l r342 0 nd nd g245n r342 casp8, mll2, notch1, rb1 fatigue f 64 n r 4 pd on surg, adj rt cps 30 8 g266r 0 nd nd g262v fgf12, mdm2, notch1, pik3ca, prkci, sox2, tert, terc m 77 fs r 5 pr on surg, adj rt tps 90% 163 v143m r248w q136 ccnd2 cdkn2a brca2 tert nd nd r248w alk, brca2, ccnd1, bard1, atr, axin1, cdkn2a/b, fgf19, fgf3, fgf4, mycn, notch1, tert lung nodules m 83 n r 5 pr on surg tps 20% 35 0 kras nd nd r213q p278f ss 751g>a asxl1, cdkn2a, dbmt3a, mll2, notch1, rb1, tert, tet2 m 80 n m 4 pd on surg net net 0 nras nd nd nd nd m 65 fs l 8 pr on surg, rt tps 10% nd t155p pten nd nd r342 r213 cdkn2a, hgf, keap1, mll2, mre11a, smarca4, tnfaip3 g = gender; a = age; l/r/m = loco-regional/recurrent/metastatic; iod = duration of treatment with immunotherapy; ior= response obtained with immunotherapy (cr = complete response, pr = partial response, pd = progression of disease); d = duration of response after immunotherapy was stopped; previous = treatments received before starting immunotherapy; pd-l1 = pd-l1 status measured in all cases with dako223 antibodies; tmb = tumor mutation burden measured by foundation medicine in tumor tissue; guardant before/after io = genomic mutations in blood tested by guardant 360 platform;f1 = genomic mutation in tumor tested by foundation; ae = adverse events; obs = observations; net = not enough tissue for testing. skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 24 treatment. eight patients had sufficient tumor tissue for genomic and pd-l1 testing. initial blood genomic testing was performed in 10 of 11 patients and in follow up in all three patients who achieved maximum response. patients with cr had pd-l1 of at least 30%. the additional tested patients have pd-l1 above 10%. the most frequently mutated tdna gene was tp53 and the second most frequently mutated gene was the notch1/2. tmb was intermediate or high in all tested patients. treatment of locally advanced unresectable, recurrent, and metastatic cscc with ici has led to a dramatic change in the management and prognosis of cscc. our series of patients with cscc has a higher than reported rate of response and especially complete response. this corresponds with high tp53 alterations (100% of patients), notch 1/2 alterations (90% of patients) and high level of expression of pd-l1 (90% patients). interestingly, pd-l1 rates were higher than previously published. conflict of interest disclosures: none funding: none corresponding author: nathan l. bowers, md, phd department of dermatology wake forest university school of medical winston-salem, nc email: nbowers@wakehealth.edu references: 1. migden mr, rischin d, schmults cd, guminski a, hauschild a, lewis kd, et al. pd-1 blockade with cemiplimab in advanced cutaneous squamous-cell carcinoma. n engl j med. 2018;379:341–51. 2. garcia-pedrero jm, martinez-camblor p, diazcoto s, et al. tumor programmed cell death ligand 1 expression correlates with nodal metastasis in patients with cutaneous squamous cell carcinoma of the head and neck. j am acad dermatol. 2017;77(3):527-533. 3. pickering cr, zhou jh, lee jj, et al. mutational landscape of aggressive cutaneous squamous cell carcinoma. clin cancer res. 2014;20(24):6582–6592. doi:10.1158/10780432.ccr-14-1768. discussion acknowledgements: medical writing support was provided by prescott medical communications group (chicago, il) with financial support from ortho dermatologics; ortho dermatologics is a division of bausch health us, llc • presented at fall clinical 2020 • october 29 november 1, 2020 • virtual novel polymeric tazarotene 0.045% lotion for moderate-to-severe acne: pooled phase 3 analysis by race fran e cook-bolden, md1; neal bhatia, md2; jonathan s weiss, md3; neil sadick, md4; stephen k tyring, md, phd5; eric guenin, pharmd, phd, mph6; anya loncaric, ms7; susan harris, ms8 1fran e. cook-bolden, md, pllc and department of dermatology, mount sinai hospital center, new york, ny; 2therapeutics clinical research, san diego, ca; 3georgia dermatology partners, and gwinnett clinical research center, inc., snellville, ga; 4department of dermatology, weill cornell medical college, new york, ny and sadick dermatology, new york, ny; 5university of texas health science center, houston, tx; 6ortho dermatologics,* bridgewater, nj; 7bausch health us, llc,* petaluma, ca; 8bausch health us, llc,* bridgewater, nj *bausch health us, llc is an affiliate of bausch health companies inc. ortho dermatologics is a division of bausch health us, llc. synopsis ■ patients with skin of color have an increased risk of acne and inflammation-related sequalae, including post-inflammatory hyperpigmentation (pih) associated with acne resolution or irritation from treatment1 ■ topical retinoids such as tazarotene treat acne by inhibiting multiple inflammatory pathways and normalizing desquamation2; however, skin irritation and other skin reactions may limit the use of some tazarotene gel and cream formulations3 ■ a recently-approved, lower-dose tazarotene 0.045% lotion formulation (arazlo™, ortho dermatologics) was developed utilizing polymeric emulsion technology (figure 1)4 • this highly spreadable lotion formulation was developed to allow for more efficient delivery of tazarotene into dermal layers while reducing the potential for skin irritation4 figure 1. polymeric emulsion technology for tazarotene 0.045% lotion 3-d mesh (polymeric matrix) holding water and water-soluble hydrating agents within the mesh droplets consisting of tazarotene and oil-soluble moisturizing agents held apart by the 3-d mesh 3-d mesh allows for uniform distribution of tazarotene and moisturizing agents 25-50 μm 1-2 μm objective ■ data from two phase 3 studies were pooled to evaluate the efficacy and safety of once-daily tazarotene 0.045% lotion compared with vehicle lotion in participants of white or black race (self-identified) methods ■ in two phase 3, double-blind, 12-week studies (nct03168334; nct03168321),5,6 participants with moderate-to-severe acne were randomized 1:1 to tazarotene 0.045% lotion or vehicle lotion (n=1614) • in these studies, cerave® hydrating cleanser and cerave® moisturizing lotion (l’oreal, ny) were provided as needed for optimal moisturization/cleaning of the skin. ■ this pooled, post hoc analysis included subsets of participants segmented by white (n=1191) or black race (n=262) ■ coprimary endpoints were inflammatory/noninflammatory lesion counts and treatment success; treatment-emergent adverse events (teaes) and cutaneous safety and tolerability were also evaluated results figure 2. participant demographics and baseline characteristics (itt population, pooled) black (n=262) white (n=1191) 24.0 years 19.6 years 26.6 28.5 40.6 40.9 mean age: % female: % non-hispanic/latino: mean in�ammatory lesion count: mean nonin�ammatory lesion count: % egss distribution (moderate and severe): 63.2%78.2% 74.2%94.3% 90% 10% 95% 5% • demographics and baseline characteristics were generally similar between subgroups, though: • black participants were on average older and more likely to be female • a higher proportion of white participants had a baseline egss of 4 (“severe”) egss, evaluator’s global severity score; itt, intent to treat. figure 3. efficacy outcomes at week 12 by race (itt population, pooled) -70% -50% -30% -10% black participants white participants black participants white participants black participants white participantsls m e a n c h a n g e f ro m b a se lin e a. in�ammatory lesion reduction b. nonin�ammatory lesion reduction -70% -50% -30% -10% ls m e a n c h a n g e f ro m b a se lin e tazarotene 0.045% lotion: • black and white participants had a similar reduction in in�ammatory and nonin�ammatory lesions by week 12 • lesion counts decreased over time in both black and white participants (data not shown) • greater percentage of black and white participants achieved treatment success vs vehicle n=125 -60.4% n=137 -57.8% n=591 -57.6% n=600 -45.0% n=125 -52.6% n=137 -44.5% n=600 -40.7% n=591 -56.1% 0% 20% 40% 60% 80% 100% p e rc e n ta g e o f p a rt ic ip a n ts n=125 29.6% n=137 19.6% c. treatment successa n=591 31.2% n=600 16.7% vehicle lotion tazarotene 0.045% lotion vehicle lotion tazarotene 0.045% lotion vehicle lotion tazarotene 0.045% lotion *p<0.05; ***p<0.001 vs vehicle. adefined as at least a 2-grade reduction from baseline in evaluator’s global severity score and a score of ‘clear’ or ‘almost clear’. itt, intent to treat; ls, least-squares. ■ rates of teaes were similar for taz-treated black and white participants; teaes were mostly mild or moderate and unrelated to treatment (table 1) table 1. participants reporting any treatment-emergent adverse event (safety population, pooled) participants, n (%) black participants white participants taz 0.045% lotion (n=121) vehicle lotion (n=132) taz 0.045% lotion (n=575) vehicle lotion (n=584) reporting any teae 30 (24.8) 17 (12.9) 165 (28.7) 118 (20.2) reporting any saea 1 (0.8) 1 (0.8) 3 (0.5) 3 (0.5) discontinued due to a teaeb 5 (4.1) 0 16 (2.8) 4 (0.7) severity of teaes reported mild 22 (18.2) 8 (6.1) 103 (17.9) 63 (10.8) moderate 7 (5.8) 7 (5.3) 54 (9.4) 53 (9.1) severe 1 (0.8) 2 (1.5) 8 (1.4) 2 (0.3) relationship to study drug related 15 (12.4) 1 (0.8) 68 (11.8) 8 (1.4) unrelated 15 (12.4) 16 (12.1) 97 (16.9) 110 (18.8) most common teaesc application site pain 8 (6.6) 0 30 (5.2) 2 (0.3) application site dryness 4 (3.3) 0 24 (4.2) 1 (0.2) application site exfoliation 6 (5.0) 0 8 (1.4) 0 viral urtia 6 (5.0) 2 (1.5) 25 (4.3) 25 (4.3) ano instances were considered by the investigator to be treatment related. bincludes participants who discontinued study drug or prematurely discontinued from the study. creported in ≥3% of participants in any treatment group. sae, serious adverse event; taz, tazarotene; teae, treatment-emergent adverse event; urti, upper respiratory tract infection. figure 4. cutaneous safety by race (safety population, pooled) 0% 20% 40% 60% 80% 100% p e rc e n ta g e o f p ar ti ci p an ts scaling erythema hypopigmentation hyperpigmentation taz vehicle taz vehicle taz vehicle taz vehicle p e rc e n ta g e o f p ar ti ci p an ts 0% 20% 40% 60% 80% 100% scaling erythema hypopigmentation hyperpigmentation taz vehicle taz vehicle taz vehicle taz vehicle tazarotene-treated participants: • high baseline rates of hyperpigmentation (black participants) and erythema (white participants) decreased by week 12 • participant-reported tolerability assessments of itching, burning, and stinging were low in both groups (data not shown) b. white participants a. black participants at baseline: at week 12: mild moderate severe mild moderate severe at baseline: at week 12: mild moderate severe mild moderate severe data for “none” are not shown. n values were as follows: black: taz baseline n=121, taz week 12 n=102, vehicle baseline n=132, vehicle week 12 n=121; white: taz baseline n=575, taz week 12 n=512, vehicle baseline n=584, vehicle week 12 n=532. taz, tazarotene 0.045% lotion. conclusions ■ in two pooled phase 3 studies, tazarotene 0.045% lotion demonstrated efficacy in the treatment of moderate-to-severe acne in both white and black participants • in white participants, tazarotene was significant versus vehicle for all 3 efficacy assessments • in black participants, only reduction in noninflammatory lesions was significant for tazarotene versus vehicle; the lack of a statistical difference in the reduction of inflammatory lesions is likely due to the high response rate to vehicle in black participants, whereas the statistical analysis of treatment success may have been limited in part by the small sample size ■ this new formulation of tazarotene was well tolerated compared with vehicle lotion, and treatment with tazarotene lotion led to improvements in inflammation-associated sequelae of acne, including hyperpigmentation ■ tazarotene 0.045% lotion may be an effective and well tolerated treatment option for acne in patients with skin of color figure 5. postinflammatory hyperpigmentation improvement in black participants baseline baseline week 12 week 12 two participants selected from a post hoc evaluation of study photographs to identify individuals who achieved improvement in postinflammatory hyperpigmentation. individual results may vary. references 1. alexis af. j drugs dermatol. 2014;13(6):s6-s10. 2. leyden j, et al. dermatol ther (heidelb). 2017;7(3):293-304. 3. del rosso jq and tanghetti e. j drugs dermatol. 2013;12(3)s53-58. 4. tanghetti ea, et al. j drugs dermatol. 2019;18(6):542 5. tanghetti ea, et al. j drugs dermatol. 2020;19(1)70-77. 6. tanghetti ea, et al. j drugs dermatol. 2020;19(3)272-279. author disclosures fcb has served as consultant, speaker, investigator for galderma, leo pharma, almirall, cassiopea, ortho dermatologics, investigators encore, foamix, hovione, aclaris, cutanea. nb has received honoraria and investigator grants from bausch health. jw a consultant, speaker, advisor, and/or researcher for abbvie, ortho dermatologics, jansen biotech, dermira, almirall, brickell biotech, dermtech, scynexis. ns has served on advisory boards, as a consultant, investigator, speaker, and/or other and has received honoraria and/or grants/research funding from almirall, actavis, allergan, anacor pharmaceuticals, auxilium pharmaceuticals, bausch health, bayer, biorasi, btg, carma laboratories, cassiopea, celgene corporation, cutera, cynosure, dusa pharmaceuticals, eclipse medical, eli lilly and company, endo international, endymed medical, ferndale laboratories, galderma, gerson lehrman group, hydropeptide, merz aesthetics, neostrata, novartis, nutraceutical wellness, palomar medical technologies, prescriber’s choice, regeneron, roche laboratories, samumed, solta medical, storz medical ag, suneva medical, vanda pharmaceuticals, and venus concept. st has acted as an investigator for ortho dermatologics. eg is an employee of ortho dermatologics and may hold stock or stock options in its parent company. al and sh are employees of bausch health us, llc and may hold stock and/or stock options in its parent company. acknowledgements: medical writing support was provided by prescott medical communications group (chicago, il) with financial support from ortho dermatologics; ortho dermatologics is a division of bausch health us, llc • presented at the pa & np fall clinical dermatology conference • june 9-11, 2023 • orlando, fl background and rationale � patient age or sex may impact the efficacy and tolerability of topical acne treatments1-3 • managing acne in younger patients is complicated by low rates of treatment adherence4 and the potential for more irritation with topical treatments than in adults5 • among adults, females may be more susceptible to dry skin, making irritation with topical treatment a significant concern6 � idp-126 fixed-dose polymeric mesh gel (clindamycin phosphate 1.2%/benzoyl peroxide [bpo] 3.1%/ adapalene 0.15%) is the first triple-combination, fixed-dose, topical acne treatment in development � idp-126 demonstrated superior efficacy to vehicle and component dyads, with good safety and tolerability, in a phase 27 and two phase 3 studies of participants with moderate-to-severe acne objective � to assess the impact of age or sex on efficacy and safety/tolerability of idp-126 gel methods � in two phase 3, double-blind, randomized studies (nct04214639, nct04214652), eligible participants aged ≥9 years with moderate-to-severe acne were randomized 2:1 to receive idp-126 or vehicle gel once daily for 12 weeks • cerave® hydrating cleanser and cerave® moisturizing lotion (l’oreal, ny) were provided as needed for optimal skin moisturization/cleaning � data from these studies were pooled and analyzed post hoc by participant age (pediatric, <18 years; adult, ≥18 years) or sex � endpoints included treatment success (≥2-grade reduction from baseline in evaluator’s global severity score [egss] and a score of 0 [clear] or 1 [almost clear]) and least-squares mean percent change from baseline in inflammatory and noninflammatory lesion counts • acne severity was assessed via egss, which was scored as: 0 (clear) = normal, clear skin/no evidence of acne; 1 (almost clear) = rare noninflammatory lesions, with rare noninflamed papules; 2 (mild) = some noninflammatory lesions, with few inflammatory lesions; 3 (moderate) = noninflammatory lesions predominate, with multiple inflammatory lesions: several/many comedones and papules/pustules, ≤1 nodulocystic lesion; 4 (severe) = inflammatory lesions more apparent, many comedones/papules/ pustules, ≤2 nodulocystic lesions � treatment-emergent adverse events (teaes) and cutaneous safety/tolerability were also assessed figure 1. treatment success a at week 12 (itt population) 40% p e rc e n ta g e o f p ar ti ci p an ts 80% 20% 52.7% <18 y 60% 121n= 24.0% 52 45.9% ≥18 y 116 23.5% 69 by age 0% 40% 80% 20% 53.7% females 60% 144n= 23.0% 68 43.1% males 98 24.6% 53 by sex 0% idp-126 gel vehicle gel *p<0.05; **p<0.01; ***p≤0.001 vs vehicle. adefined as percentage of participants achieving ≥2-grade reduction from baseline in egss and a score of 0 (clear) or 1 (almost clear). values have been adjusted for multiple imputation. egss, evaluator’s global severity score; idp-126, clindamycin phosphate 1.2%/benzoyl peroxide 3.1%/ adapalene 0.15%; itt, intent to treat. figure 2. lesion reduc tions from baseline to week 12 (itt population) -40% ls m e an p e rc e n t c h an g e f ro m b as e lin e -80% <18 y -20% by age -100% -60% -78.6% 126n= -50.4% 52 ≥18 y -76.6% 116 -62.8% 69 0% -40% -80% females -20% by sex -100% -60% -77.7% 144n= -57.9% 68 males -77.5% 98 -57.1% 53 0% in�ammatory lesions -40% ls m e an p e rc e n t c h an g e f ro m b as e lin e -80% <18 y -20% by age -100% -60% -73.8% 126n= -41.1% 52 ≥18 y -70.7% 116 -52.2% 69 0% -40% -80% females -20% by sex -100% -60% -72.5% 144n= -45.6% 68 males -72.3% 98 -49.6% 53 0% nonin�ammatory lesions idp-126 gel vehicle gel ***p≤0.001 vs vehicle. values have been adjusted for multiple imputation. idp-126, clindamycin phosphate 1.2%/benzoyl peroxide 3.1%/adapalene 0.15%; itt, intent to treat; ls, least squares. impact of age or sex on efficacy and safety of a fixed-dose clindamycin phosphate 1.2%/benzoyl peroxide 3.1%/adapalene 0.15% gel in participants with moderate-to-severe acne linda stein gold, md,1 leon h kircik, md,2-4 william philip werschler, md,5 hilary baldwin, md,6,7 valerie callender, md,8,9 lawrence green, md,10 neil sadick, md,11,12 jeffrey l sugarman, md, phd,13 zoe d draelos, md,14 emil a tanghetti, md,15 neal bhatia, md16 1henry ford hospital, detroit, mi; 2icahn school of medicine at mount sinai, new york, ny; 3indiana university medical center, indianapolis, in; 4physicians skin care, pllc, dermresearch, pllc, and skin sciences, pllc, louisville, ky; 5elson s. floyd college of medicine, washington state university, spokane, wa; 6the acne treatment and research center, brooklyn, ny; 7robert wood johnson university hospital, new brunswick, nj; 8callender dermatology and cosmetic center, glenn dale, md; 9howard university college of medicine, washington dc; 10george washington university school of medicine, washington, dc; 11weill cornell medical college, new york, ny; 12sadick dermatology, new york, ny; 13university of california, san francisco, ca; 14dermatology consulting services, pllc, high point, nc; 15center for dermatology and laser surgery, sacramento, ca; 16therapeutics clinical research, san diego, ca figure 3. acne improvements with idp-126 gel baseline egss: 4 il: 51 nil: 40 14-year-old female – white, non-hispanic week 12 egss: 2 il: 10 (-80%) nil: 8 (-80%) baseline egss: 3 il: 43 nil: 47 25-year-old female – black, hispanic week 12 egss: 2 il: 2 (-95%) nil: 14 (-70%) baseline egss: 3 il: 53 nil: 55 16-year-old male – white, non-hispanic week 12 egss: 1 il: 7 (-87%) nil: 9 (-84%) baseline egss: 3 il: 48 nil: 49 44-year-old male – asian, non-hispanic week 12 egss: 0 il: 0 (-100%) nil: 2 (-96%) individual results may vary. egss, evaluator’s global severity score; idp-126, clindamycin phosphate 1.2%/benzoyl peroxide 3.1%/adapalene 0.15%; il, inflammatory lesions; nil, noninflammatory lesions. table 1. summary of adverse events through week 12 (safety population) n (%) <18 years ≥18 years females males idp-126 (n=126) veh (n=52) idp-126 (n=116) veh (n=69) idp-126 (n=144) veh (n=68) idp-126 (n=98) veh (n=53) teaes 32 (25.4) 3 (5.8) 34 (29.3) 7 (10.1) 39 (27.1) 6 (8.8) 27 (27.6) 4 (7.5) related 23 (18.3) 0 25 (21.6) 2 (2.9) 28 (19.4) 2 (2.9) 20 (20.4) 0 not related 9 (7.1) 3 (5.8) 9 (7.8) 5 (7.2) 11 (7.6) 4 (5.9) 7 (7.1) 4 (7.5) serious aes 0 0 0 0 0 0 0 0 discontinued drug/study due to teae 3 (2.4) 0 4 (3.4) 0 4 (2.8) 0 3 (3.1) 0 most common treatment-related teaes (≥2% participants in any treatment) as pain 16 (12.7) 0 15 (12.9) 1 (1.4) 16 (11.1) 1 (1.5) 15 (15.3) 0 as dryness 3 (2.4) 0 4 (3.4) 0 3 (2.1) 0 4 (4.1) 0 erythema 3 (2.4) 0 3 (2.6) 0 2 (1.4) 0 4 (4.1) 0 as irritation 1 (0.8) 0 4 (3.4) 0 4 (2.8) 0 1 (1.0) 0 xerosis 0 0 3 (2.6) 1 (1.4) 3 (2.1) 1 (1.5) 0 0 as exfoliation 2 (1.6) 0 2 (1.7) 0 3 (2.1) 0 1 (1.0) 0 as, application site; idp-126, clindamycin phosphate 1.2%/benzoyl peroxide 3.1%/adapalene 0.15% gel; teae, treatment-emergent adverse event; veh, vehicle gel. results participants � the 363 participants in the overall pooled population were evenly divided between pediatric and adult participants (n=178 and 185, respectively); overall, almost 60% were female (n=212) � across all subgroups, most participants were white (68.6%78.7%) and non-hispanic (76.9%79.5%), with baseline egss score of 3 (moderate; 87.4%-93.9%) efficacy � at week 12, over half of pediatric and almost half of adult idp-126-treated participants achieved treatment success, versus one-fourth with vehicle; results by sex were similar (figure 1) � at week 12, idp-126 provided >70% reductions in inflammatory/ noninflammatory lesions in all subgroups; reductions were significantly greater versus vehicle (figure 2) � differences in rates of treatment success and percent reductions from baseline in inflammatory and noninflammatory lesions were not statistically significant between idp-126–treated age or sex subgroups � images of representative idp-126– treated participants from each subgroup are shown in figure 3 safety and tolerability � teae rates/severity/relationship to study drug, and the most common teaes, were similar across age and sex subgroups (table 1) • most teaes were of mild-tomoderate severity (data not shown) � rates of idp-126 discontinuations due to teaes were low (<4%) in all subgroups � mean scores for cutaneous safety and tolerability assessments (erythema, scaling, hyperpigmentation, hypopigmentation, itching, burning, and stinging) were <1 (mild) at all study visits (data not shown) conclusions � the innovative fixed-dose, triple-combination idp-126 gel (clindamycin phosphate 1.2%/benzoyl peroxide 3.1%/adapalene 0.15%) was efficacious and well tolerated, regardless of age or sex, in participants with moderate-to-severe acne • at week 12, approximately half of participants achieved treatment success with idp-126 gel versus less than one fourth with vehicle • in all subgroups, idp-126 provided over 70% reductions from baseline in inflammatory and noninflammatory lesions � the efficacy and favorable safety profile of idp-126 gel in children, adults, females and males demonstrate its potential as a topical treatment option for acne in a variety of patient populations references 1. tanghetti e. j drugs dermatol. 2012;11(12):1417-1421. 2. stein gold l. j drugs dermatol. 2019;18(12):1218-1225. 3. cook-bolden f. j drugs dermatol. 2020;19(1):78-85. 4. hester c, et al. pediatr dermatol. 2016;33(1):49-55. 5. kraft j and freiman a. cmaj. 2011; 183(7):e430-435. 6. zeichner ja, et al. j clin aesthet dermatol. 2017;10(1):37-46. 7. stein gold l, et al. am j clin dermatol. 2022;23(1):93-104. author disclosures lsg has served as investigator/consultant or speaker for ortho dermatologics, leo pharma, dermavant, incyte, novartis, abbvie, pfizer, sun pharma, ucb, arcutis, and lilly. lk has acted as an investigator, advisor, speaker, and consultant for ortho dermatologics. wpw has served as an investigator for ortho dermatologics. hb has served as advisor, investigator, and on speakers’ bureaus for almirall, cassiopea, foamix, galderma, ortho dermatologics, sol gel, and sun pharma. vc has served as an investigator, consultant, or speaker for abbvie, galderma, l’oréal, ortho dermatologics, and vyne. lg has served as investigator, consultant, or speaker for almirall, cassiopea, galderma, ortho dermatologics, sol gel, sun pharma, and vyne. ns has served on advisory boards, as a consultant, investigator, speaker, and/or other and has received honoraria and/or grants/research funding from almirall, actavis, allergan, anacor pharmaceuticals, auxilium pharmaceuticals, bausch health, bayer, biorasi, btg, carma laboratories, cassiopea, celgene corporation, cutera, cynosure, dusa pharmaceuticals, eclipse medical, eli lilly and company, endo international, endymed medical, ferndale laboratories, galderma, gerson lehrman group, hydropeptide, merz aesthetics, neostrata, novartis, nutraceutical wellness, palomar medical technologies, prescriber’s choice, regeneron, roche laboratories, samumed, solta medical, storz medical ag, suneva medical, vanda pharmaceuticals, and venus concept. jls is a consultant for ortho dermatologics, bausch health, regeneron, sanofi, verrica, and pfizer. zdd has received funding from ortho dermatologics. eat has served as speaker for novartis, ortho dermatologics, sun pharma, lilly, galderma, abbvie, and dermira; served as a consultant/clinical studies for hologic, ortho dermatologics, and galderma; and is a stockholder for accure. nb has served as advisor, consultant, and investigator for abbvie, almirall, biofrontera, bi, brickell, bms, epi health, ferndale, galderma, incyte, isdin, j&j, laroche-posay, leo pharma, ortho dermatologics, regeneron, sanofi, sunpharma, verrica, and vyne. skin january 2019 volume 3 issue 1 copyright 2018 the national society for cutaneous medicine 39 brief articles langerhan's cell histiocytosis masquerading as intertrigo matthew a cornacchia, bs,1 david munger, do,2 vaagn andikyan, md,3 charles l halasz, md,4 1ross university school of medicine, miramar, fl 2department of radiology, norwalk hospital, norwalk, ct 3university of vermont, western connecticut health network, vt 4department of dermatology, columbia university, new york, ny langerhan’s cell histiocytosis (lch) is a clonal neoplastic disease of the langerhan’s cell1. langerhan’s cell histiocytosis was first described by dr. alfred hand in 1893, although he incorrectly attributed the presentation to tuberculosis2. subsequently a heterogenous group of diseases were described, mainly in children and eventually unified under the name histocytosis x in 1953 and then finally langerhan’s cell histiocytosis in 1987 once the cell of origin was elucidated3. langerhan’s cell histiocytosis is a disease primarily of children, with a smaller second peak occurring in adults and is rare in the elderly4. langerhan’s cell histiocytosis is classified based on the number of organ systems involved and focality of the lesions1. although the etiology of lch is unknown, a recent study shows that approximately half of lch cases have an activating braf v600e mutation, suggesting that it is a neoplastic rather than a hyperplastic process5. we present a case of an elderly patient with langerhan’s cell histiocytosis that had been misdiagnosed and treated for over a year as severe, refractory intertrigo. a 70 year old caucasian female presented with a 1 year history of painful rash involving the inframammary and inguinal folds, vulva and scalp. the vulvar erosions were causing dysuria. her past medical history was significant for diabetes insipidus, diagnosed 7 years prior, treated with desmopressin cutaneous langerhan’s cell histiocytosis (lch) is considered a great clinical mimicker that affects the scalp and intertriginous regions although it may be generalized. cutaneous lch is commonly misdiagnosed and thus patients can receive inadequate or inappropriate treatment for considerable periods of time. we present a case report of a patient who had lch that was masquerading as intertrigo for years. with the proper diagnosis the patient had a remarkable response to methotrexate. this case highlights the importance of keeping langerhan’s cell histiocytosis (lch) on the differential and once the diagnosis is made, evaluating for extracutaneous lch. abstract introduction case report skin january 2019 volume 3 issue 1 copyright 2018 the national society for cutaneous medicine 40 intranasal spray bid three days a week, hypertension treated with carvedilol and diverticulitis requiring a hartman procedure and subsequent colostomy reversal. prior to presentation she was treated with many antifungals in varied formulations including oral, topical and vaginal suppository. she stated none of these seemed to work so she has been using vaseline and gold bond powder. physical exam revealed a scalp with thick yellow adherent scale also present along the hair shafts. the bilateral inframammary and inguinal creases exhibited beefy red-purple eroded and macerated plaques with purulent drainage (figure 1 and 2). purple-red edematous plaques with purulent drainage were observed on the labia majora. laboratory studies were unremarkable except for a bacterial culture which grew methicillin sensitive staph aureus, alpha hemolytic strep, and gamma strep, and a fungal culture positive for candida albicans, taken from the inframammary fold. complete metabolic panel was unremarkable with the exception of alkaline phosphatase 431 (reference range 35-105 u/l). the patient was treated with a 7 day course of cephalexin and 4 day course of fluconazole without resolution in symptoms. punch biopsies were obtained from the abdomen. punch biopsies of the central and left abdomen revealed an atypical infiltrate that filled the papillary dermis with epidermotropism consisting of large cells with abundant cytoplasm and reniform-type nuclei admixed with eosinophils (figure 3). the atypical cells stained strongly for cd1a and s100 and were negative for melan-a. the findings were consistent with langerhan’s cell histiocytosis. figure 1 and 2: erythematous plaques present on the inframammary folds. cutaneous lch is considered a great clinical mimicker that affects the scalp and intertriginous regions although it may be generalized. cutaneous lch is commonly misdiagnosed as intertrigo, eczema, inverse psoriasis, and when present in the scalp it may be misdiagnosed as seborrheic dermatitis1. skin-limited lch is rare, as occult multisystem disease is identified in most patients following systematic work up1. a mayo clinic cohort of 314 patients aged 2 months to 83 years, revealed only 14 patients with isolated mucocutaneous lch4. this highlights the importance of fully staging a patient who is diagnosed with lch. full discussion skin january 2019 volume 3 issue 1 copyright 2018 the national society for cutaneous medicine 41 figure 3: histopathology showing atypical infiltrated filling the papillary dermis with epidermotropism and abundant cytoplasm. staging includes complete blood count and metabolic panel (including liver enzymes), coagulation studies, thyroid stimulating hormone, free t4, urinalysis, skeletal survey (including a skull series), and chest x-ray1. treatment of lch with localized cutaneous involvement includes topical nitrogen mustard 20% and phototherapy 1. for mild symptoms, with no “risk organs” involved including bone marrow, liver, spleen and cns, methotrexate 20mg po/iv weekly, azathioprine 2mg/kg/day po or thalidomide 100mg daily po are recommended1. our patient had mucocutaneous lch involving the vulva, scalp and intertriginous creases with likely pituitary involvement given the preceding diagnosis of diabetes insipidus with no obvious findings on the brain mri at the time of diagnosis, 7 years prior. pituitary disease is most commonly due to osseous involvement1. after the diagnosis of lch was made, a skeletal survey was performed and was negative, despite the alkaline phosphatase elevation. the patient was started on methotrexate increasing from 15mg once weekly after the first month to 25 mg once weekly. there was significant improvement in degree of maceration after 5 months of therapy (figure 4). the elevated alkaline phosphatase subsequently responded to methotrexate therapy, raising the question of possible subclinical osseous involvement. langerhan’s cell histocytosis is a rare dermatosis that should remain on the differential for patients presenting with refractory intertrigo. once the diagnosis is determined, a full staging as outlined above should be performed and will dictate the aggressiveness of treatment. conflict of interest disclosures: none. funding: none. corresponding author: mary gail mercurio, md university of rochester rochester, ny marygail_mercurio@urmc.rochester.edu references: 1. girschikofsky m, arico m, castillo d et al. management of adult patients with langerhans cell histiocytosis: recommendations from an expert panel on behalf of euro-histio-net. orphanet j rare dis. 2013 may 14;8:72. 2. hand a jr. 1893. polyuria and tuberculosis. arch. pediatr. 10:673–75 3. badalian-very g, vergilio ja, fleming m, rollins bj. pathogenesis of langerhans cell histiocytosis. annu rev pathol. 2013 jan 24;8:1-20. 4. howarth dm, gilchrist gs, mullan bp, wiseman ga, edmonson jh, schomberg pj. langerhans cell histiocytosis: diagnosis, natural history, management, and outcome. cancer. 1999 may 15;85(10):2278-90. 5. badalian-very g1, vergilio ja, degar ba et al. recurrent braf mutations in langerhans cell histiocytosis. blood. 2010 sep 16;116(11):1919-23. mailto:marygail_mercurio@urmc.rochester.edu https://www.ncbi.nlm.nih.gov/pubmed/?term=howarth%20dm%5bauthor%5d&cauthor=true&cauthor_uid=10326709 https://www.ncbi.nlm.nih.gov/pubmed/?term=gilchrist%20gs%5bauthor%5d&cauthor=true&cauthor_uid=10326709 https://www.ncbi.nlm.nih.gov/pubmed/?term=mullan%20bp%5bauthor%5d&cauthor=true&cauthor_uid=10326709 https://www.ncbi.nlm.nih.gov/pubmed/?term=mullan%20bp%5bauthor%5d&cauthor=true&cauthor_uid=10326709 https://www.ncbi.nlm.nih.gov/pubmed/?term=wiseman%20ga%5bauthor%5d&cauthor=true&cauthor_uid=10326709 https://www.ncbi.nlm.nih.gov/pubmed/?term=edmonson%20jh%5bauthor%5d&cauthor=true&cauthor_uid=10326709 https://www.ncbi.nlm.nih.gov/pubmed/?term=edmonson%20jh%5bauthor%5d&cauthor=true&cauthor_uid=10326709 https://www.ncbi.nlm.nih.gov/pubmed/?term=schomberg%20pj%5bauthor%5d&cauthor=true&cauthor_uid=10326709 https://www.ncbi.nlm.nih.gov/pubmed/?term=badalian-very%20g%5bauthor%5d&cauthor=true&cauthor_uid=20519626 https://www.ncbi.nlm.nih.gov/pubmed/?term=vergilio%20ja%5bauthor%5d&cauthor=true&cauthor_uid=20519626 https://www.ncbi.nlm.nih.gov/pubmed/?term=degar%20ba%5bauthor%5d&cauthor=true&cauthor_uid=20519626 skin may 2018 volume 2 issue 3 copyright 2018 the national society for cutaneous medicine 186 original research incorporating discussion of seborrheic keratoses during primary care visits keith wagner ms a , daniel juarez md b , bernard gibson md a a department of dermatology, the university of texas medical branch, galveston, tx b primary care clinic, san antonio, tx seborrheic keratoses (sk) are a common benign epidermal neoplasm. the prevalence of sk increases with age and may be related to sun exposure. 1 although sk are often asymptomatic, they can itch, bleed, or become irritated, especially if they are traumatized. patients may also be concerned about sk because of cosmetic disfigurement or skin cancer fears. given that sk are so common, and primary care visits comprise such 52.2% of total health care visits 2 , it is likely that primary care physicians will see a very high volume of sk in their practices. a quality improvement project (qip) was undertaken to determine if patients with chronic medical conditions in a primary care general internal medicine practice have worries about their sk that could be addressed during these clinical encounters. english and spanish speaking patients age 65+ from a primary care outpatient clinic in san antonio, texas presenting for nonabstract seborrheic keratoses are a common benign epidermal neoplasm in the elderly. primary care physicians caring for adult and geriatric populations will observe them regularly during the physical examinations they perform on their patients. this quality improvement project was developed to determine if primary care physicians could provide additional benefit to their patients during office visits by addressing the concerns they may have about seborrheic keratoses. data gathered by this project indicates that some patients could benefit from reassurance that their seborrheic keratoses are not skin cancer, or by making dermatology referrals if patient seborrheic keratoses are symptomatic, particularly if they are pruritic or bleeding. in addition, some patients may welcome a referral to a dermatologist who will be able to address any cosmetic concerns related to seborrheic keratoses, especially when they are present in visibly sensitive areas such as the face and hands. introduction methods skin may 2018 volume 2 issue 3 copyright 2018 the national society for cutaneous medicine 187 dermatologic issues were asked structured and open-ended questions about sk and inspected for these benign epidermal tumors (box 1). patients were also excluded if they had dementia. dementia was investigated by chart history, patient admission, or confirmation by a relative who attended the visit with the patient. a likert scale with response choices ranging from 1 to 5 was also used to determine how much sk bothered each patient, with “1” indicating no bother at all and “5” indicating significant distress. descriptive statistics were used to analyze data. all patients were reassured by their primary care physician that their sk were benign and not skin cancer. referrals were offered to dermatologists when the sk were symptomatic for evaluation and management. qips are currently exempt from irb oversight at this institution. four participants of the 23 who volunteered to be examined for sk demonstrated no sk. no patients were excluded for dementia. twelve men and seven women ranging from 65 to 89 years old (mean age 75.6 years) had sk on physical examination. the back was the most common location for sk (n=17), followed by the chest (n=14), face (n=11), abdomen (n=8), arm and hands (n=5), and leg and foot (n=2). fourteen patients, several with multiple concerns, indicated that they were displeased with their sk by scoring higher than a 1 on the bother score (6), having worries about skin cancer (5), itching (5), having specific complaints about their sk obtained during open-ended questioning (4), or bleeding (2). of the six patients reporting symptomatic sk (itching or bleeding), 3 patients had more than 20 sk, 2 had between 11 and 20 sk, and 1 had between 1 and 10. for the 5 patients found to be worried about skin cancer, only 2 asked the examining physician about it. the likert scale mean for the entire group of participants for sk was 1.4, the same as for the 5 participants that were worried that their sk were skin cancer. however, when the 6 patients were analyzed who had symptomatic sk (itching or bleeding) the likert scale mean was 1.7. the highest likert scale scores recorded were 3s by two women, one with a pruritic sk and the other who complained that she did not like their appearance. three participating patients previously had seborrheic keratoses destroyed by liquid nitrogen or by surgical removal. seborrheic keratoses were very common among the participating group, with 79% (19/24) of examined participants having at least one seborrheic keratosis. in 2015 it was estimated that 84 million americans have sk. 3 skin disease is a rapidly growing area of medical expense. additionally, it has been estimated that skin disease results in 56.2 billion dollars in quality of life losses. 4 some patients presenting to dermatology practices are unhappy with their sk and are interested in treatment. 5 the number of patients with sk who complained of itching, bleeding, being bothered, worried about cancer, or had previously had sk removed was 14 (74%). it is interesting that despite patient concerns and occasional destructive treatment interventions, the likert scale scores were relatively low, even for the subgroups with skin cancer concerns (1.4) and the group experiencing symptoms of itching and bleeding (1.7). a possible explanation for the relatively low likert scale scores found in this primary care internal medicine practice is that none of these patients presented with results discussion skin may 2018 volume 2 issue 3 copyright 2018 the national society for cutaneous medicine 188 box 1. seborrheic keratosis quality improvement primary care provider tool skin may 2018 volume 2 issue 3 copyright 2018 the national society for cutaneous medicine 189 a chief complaint of sk, and that all participants were are at their appointment for the management of multiple chronic health conditions such as diabetes mellitus, chronic obstructive pulmonary disease, congestive heart failure, and hypertension. this context of sk together with systemic illnesses could be causing patients to evaluate their sk concerns relatively lower compared to their primary medical issues. this qip indicates that there is potential patient benefit for primary care physicians to address patient concerns when sk are found on physical exams in their adult and geriatric patients. additionally, since the back is the most frequent site for melanoma in the united states and this area of the body is difficult for patients to see, physician reassurance that there are only sk on the back and that no melanoma is present should be of great value. among the effective and minimally invasive treatments of sk are cryotherapy for patients with relatively little pigmentation and electrodessication for patients with more melanin. 6 referral for sk that are symptomatic or atypical in appearance, possibly indicative of non-melanoma skin cancer or melanoma, is always appropriate. however, if sk are not symptomatic, their treatment is considered to be cosmetic. important research by del rosso indicates that patients with cosmetic concerns about sk may welcome referral to dermatologists that can address this cosmetic concern. 5 it would be potentially beneficial to patient well-being if primary care physicians addressed patients concerns about sk during regular or non-emergent physical examinations. this is especially true considering the volume of patients that primary care physician likely see. the tool used in our qip appears to be an easilyimplementable provider instrument that could help to ensure streamlined attention to primary care patients with sk lesions. however, this qip report is based on the primary care practice of one physician in an urban setting; any practice considering implementation of this process should consider adapting the tool to their own workflow and setting. furthermore, future plan-do-study-act cycles in our program should examine the effect of this protocol on dermatology referral rates. patients should be reassured that sk are not cancer, and that if they are symptomatic, there are several minimally invasive and effective treatment options available. when asking patients about their sk in primary care practices, physicians and investigators should be aware that patients may be comparing their sk concerns relative to their general health complaints, resulting in understatement of their sk concerns. conflict of interest disclosures: none funding: none corresponding author: keith d. wagner, ms department of dermatology 301 university blvd. 4.112, mccullough bldg. galveston, tx 77555 409-747-3376 (office) 409-772-4456 (fax) kedwagne@utmb.edu conclusion skin may 2018 volume 2 issue 3 copyright 2018 the national society for cutaneous medicine 190 references: 1. yeatman j, kilkenny m, marks, r. the prevalence of seborrheic keratoses in an australian population: does exposure to sunlight play a part in their frequency? br j dermatol. 1997;137(3):411-414. 2. centers for disease control and prevention. (2010). national ambulatory medical care survey: 2014 state and national summary tables, tables 1, 11, 16. available at: https://www.cdc.gov/nchs/data/ahcd /namcs_summary/2014_namcs_web_t ables.pdf. accessed december 20, 2017. 3. jackson j, alexis a, berman b, et al. current understanding of seborrheic keratosis: prevalence, etiology, clinical presentation, diagnosis, and management. j drugs dermatol. 2015;14(10):1119-1125. 4. bickers d, lim h, margolis d, et al. the burden of skin diseases: 2004: a joint project of the american academy of dermatology association and the society for investigative dermatology. j am acad dermatol. 2006;55(3):490500. 5. del rosso j. a closer look at seborrheic keratoses: patient perspectives clinical relevance, medical necessity, and implications for management. j clinl aesthet dermatol. 2017;10(35):16-25. 6. ranasinghe g, friedman, a. managing seborrheic keratoses: evolving strategies for optimizing patient outcomes. j drugs dermatol. 2017;16(11):1064-1068. https://www.cdc.gov/nchs/data/ahcd/namcs_summary/2014_namcs_web_tables.pdf https://www.cdc.gov/nchs/data/ahcd/namcs_summary/2014_namcs_web_tables.pdf https://www.cdc.gov/nchs/data/ahcd/namcs_summary/2014_namcs_web_tables.pdf https://www.cdc.gov/nchs/data/ahcd/namcs_summary/2014_namcs_web_tables.pdf microsoft word 7. 376 proof done.docx skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 57 brief articles subcorneal pustular dermatosis successfully treated with acitretin in a patient with glucose-6-phoshate dehydrogenase deficiency hosseinipour, mojgan do,1 baigrie, dana do,2 crane, jonathan do2 1department of dermatology at st. barnabas hospital, bronx, ny 2department of dermatology at campbell university school of osteopathic medicine sampson regional medical center, clinton, nc a 71-year-old african american woman presented for evaluation of a painful and pruritic rash of the right lower extremity that had developed one year prior. she was referred by her primary care physician after treatment with trimethoprimsulfamethoxazole and clotrimazole for suspected bacterial and dermatophyte infection without resolution. at the dermatology office, she was initially evaluated by a physician assistant and found to have excoriated plaques on the right proximal pretibial region and right distal calf. a shave biopsy was performed revealing an impetiginized nummular dermatitis. triamcinolone acetonide 0.1% ointment was prescribed for twice daily use with modest improvement in her skin lesions. she was eventually diagnosed with pustular psoriasis based on clinical findings and started on topical treatment with calcipotriene 0.005% topical ointment to use twice daily. upon follow-up evaluation four months later, the rash continued to spread and the patient reported draining lesions and worsening pruritus despite compliance with topical therapy. at this visit, she was evaluated by the dermatologist. on examination, the patient was found to have crops of erythematous scaly papules and plaques studded with pustules distributed on the trunk, upper and lower extremities (figure 1-4). two punch biopsies were performed and direct immunofluorescence (dif) was requested. the patient was instructed to discontinue calcipotriene and begin prednisone 20 mg daily for one week. on follow-up evaluation one week later, annular and serpiginous erythematous patches and peripheral case report subcorneal pustular dermatosis (spd) is a rare neutrophilic dermatosis. spd most commonly presents as a serpiginous pattern of pustules on the trunk or intertriginous areas of middleaged females. it tends to have a chronic disease course and patients may experience relapses. dapsone currently remains the treatment of choice for spd. however, in patients with glucose6-phosphate dehydrogenase (g6pd) deficiency, alternative therapies are required. we report a case of subcorneal pustular dermatosis in a g6pd deficient patient successfully treated with acitretin. abstract skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 58 pustules were noted on physical examination. the pathology results revealed subcorneal collections of neutrophils with negative dif study (figure 5). based on clinical and histopathological examination, findings were most consistent with subcorneal pustular dermatosis. the patient was counseled on the risks, benefits and alternatives to starting dapsone therapy. a glucose-6-phosphate dehydrogenase (g6pd) level and baseline labs were ordered prior to initiating treatment with dapsone. she was found to be g6pd deficient on repeated laboratory analysis. therefore, she was started on acitretin 25mg once daily in addition to a one-week course of oral corticosteroids. the patient was also evaluated by her primary care physician in search of a gammopathy or associated comorbidity, which was unremarkable. the patient has shown immense clinical improvement on acitretin with minimal to no adverse effects. after approximately eight months of therapy with acitretin, the lesions cleared with some residual post-inflammatory hyperpigmentation. the patient experienced a relapse of her skin disease and was restarted on acitretin 25mg once daily and subsequently increased to 25mg twice daily. once she maintained clearance, she was titrated down to acitretin 25mg once daily and remained well-controlled on a scheduled dose of 25mg every other day. • subcorneal pustular dermatosis is a rare, chronic, pustular eruption typically presenting in middle-aged women on the trunk, in intertriginous areas and on the limbs. • although the mainstay of therapy is dapsone, oral retinoids may produce rapid and complete resolution of symptoms for patients in which dapsone is contraindicated. figure 1. scaly erythematous papules studded with pustules distributed on anterolateral upper extremity. figure 2. scaly erythematous papules studded with pustules distributed on posterior upper extremity. practice points skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 59 figure 3. scaly erythematous papules studded with pustules distributed on lateral lower extremity. figure 4. scaly erythematous papules studded with pustules distributed on upper anterior trunk. figure 5. h&e demonstrating subcorneal collections of neutrophils subcorneal pustular dermatosis, also referred to as sneddon-wilkinson disease, is a rare, pruritic, pustular eruption that is distributed typically on the trunk, intertriginous areas and limbs. it commonly presents in middle-aged women and may be associated with lymphoproliferative disorders such as iga or igg gammopathies or myelomas. the condition may also be associated with cancer, infection, medications or systemic or autoimmune diseases.1 the primary cutaneous lesion is a superficial, flaccid pustule arising on a somewhat erythematous base that subsequently ruptures and develops crusting or scale. the lesions may coalesce to form an annular or serpiginous pattern and tend to be symmetrically distributed.1 the etiology of subcorneal pustular dermatosis is unknown. the condition tends to have a chronic course with relapses and remissions over many years.2 the pathophysiology of subcorneal pustular comment skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 60 dermatosis is believed to be migration of neutrophils to the epidermis to form sterile pustules.3 histopathology is characterized by subcorneal pustules with abundant neutrophils, absence of acantholysis and spongiosis, and negative direct immunofluorescence.4 the absence of acantholysis and spongiosis is what distinguishes spd from impetigo histopathologically. spd must also be distinguished from iga pemphigus which will demonstrate immunoblotting with autoantigen human desmocollin 1. other histologic differentials include pustular psoriasis and superficial bacterial and fungal infections.5 the most likely diagnoses to consider in this patient are spd and pustular psoriasis. we favor spd because the patient presented with recurrent annular pustular lesions that tended to expand peripherally over a chronic period and resolve with hyperpigmentation. the histopathology exhibited subcorneal pustules without significant spongiform features. sanchez et al. report a relationship between spd and pustular psoriasis, and consider spd a part of the spectrum of pustular psoriasis, specifically the annular presentation. however, these patients tend to present in childhood and have a personal or family history of psoriasis. in many cases, these patients eventually progress into pustular psoriasis, and the typical histopathologic features of acanthosis, parakeratosis and dilated blood vessels are evident.6 in pustular psoriasis of the annular pattern, lesions can present with pain and expand more acutely in a centrifugal pattern over a period of days. patients may also experience systemic symptoms including fever and malaise, and may require hospitalization. in contrast, patients with spd present with a more benign course.7 both spd and pustular psoriasis can present clinically and histopathologically similar, which can be diagnostically challenging. the treatment of choice is dapsone at a dose of 50-200mg daily, which typically produces complete remission within 4 weeks. however, our patient had g6pd deficiency, an inherited x-linked metabolic disorder that affects red blood cell function. unlike most cells in the body, red blood cells only have one enzyme to catalyze dehydrogenase reactions necessary for metabolism. metabolism of dapsone produces toxic metabolites with directly-acting hemolytic properties.8 in patients with decreased activity of the g6pd enzyme, red blood cells become more vulnerable to oxidative stress resulting in acute hemolytic anemia. retinoids such as acitretin have comparable efficacy to dapsone. they act more rapidly and are better tolerated. previous literature report eruptions healing within 2 weeks of therapy and complete clearance within 8 months.2 acitretin is believed to exert its therapeutic effects by inhibiting neutrophil migration and function.2,3 most patients tend to have dramatic improvement of symptoms within 1 week of starting low-dose retinoids. unlike dapsone, toxicities are not a limiting factor for treatment with acitretin. dapsone has risk for serious toxicities such as hemolytic anemia and methemoglobinemia. treatment can be refractory in many cases requiring maintenance therapy to prevent relapses.1,4 with low-dose acitretin, 0.5mg/kg/day, the most frequently report adverse effect was cheilitis.2,3,4 alternative treatments including corticosteroid therapy and phototherapy are less effective. subcorneal pustular dermatosis is a rare neutrophillic skin disorder that can significantly impact a patient’s quality of life. it typically presents in middle-aged women as polycyclic or serpiginous pustules that conclusion skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 61 rupture and form superficially crusted plaques. though lesions may resolve relatively rapidly (within approximately four weeks) when treated with dapsone, certain situations such as failed response or contraindications to therapy may necessitate alternative treatments considerations. our patient was g6pd deficient, therefore dapsone was dismissed as a treatment option and the patient was started on acitretin, an oral retinoid. she remains clear and off of the medication eight months after treatment initiation. conflict of interest disclosures: none funding: none corresponding author: dana baigrie do department of dermatology sampson regional medical center 1099 medical center drive #201 wilmington nc 28412 phone: 850-241-6862 fax: 910-343-6006 e-mail: dbaigrie@vcom.edu references: 1. cohen pr. sweet's syndrome a comprehensive review of an acute febrile neutrophilic dermatosis. orphanet j rare dis. 2007;2:34. 2. canpolat f, akpinar h, cemil bc, eskioglu f, ozturk e. a case of subcorneal pustular dermatosis in association with monoclonal iga gammopathy successfully treated with acitretin. j dermatolog treat 2010; 21: 114-6. 3. marlière v, beylot-barry m, beylot c, doutre m. successful treatment of subcorneal pustular dermatosis (sneddon–wilkinson disease) by acitretin: report of a case. dermatology. 1999;199:153–155. 4. teixeira m, alves r, selores m. subcorneal pustular dermatosis in association with a monoclonal ıga gammopathy: successful treatment with acitretin. eur j dermatol. 2006;16:588–590. 5. james, w. d., elston, d. m., berger, t. g., & andrews, g. c. seborrheic dermatitis, psoriasis, recalcitrant palmoplantar eruptions, pustular dermatitis, and erythroderma in andrews' diseases of the skin: clinical dermatology. 2011;10(3)185-198. 6. sanchez, np, ho perry, sa muller, r k winkelmann. subcorneal pustular dermatosis and pustular psoriasisa clinicopathologic correlation. arch dermatol. 1983;119(9):715-721. 7. khosravi-hafshejani t, dutz jp. chronic annular pustular psoriasis resembling subcorneal pustular dermatosis: a case report. sage open med case rep. 2019;7:2050313x19857392. 8. luzzatto l., nannelli c. & notaro r. glucose-6phosphate dehydrogenase deficiency. hematol oncol clin n. 2016;30:373–93. emollient cp=clobetasol propionate; ingmeb=ingenol mebutate. figure 1 was republished with permission of journal of american academy of dermatology from topical corticosteroid has no influence on inflammation or efficacy after ingenol mebutate treatment of grade i to iii actinic keratoses (ak): a randomized clinical trial, erlendsson am, et al. j am acad dermatol 2016 apr;74(4):709-15. evaluation of different approaches in managing local skin reactions with the use of ingenol mebutate 0.015% and 0.05% during the treatment of actinic keratosis scott freeman,1 miriam bettencourt,2 meg corliss,3 nikeshia dunkelly-allen,3 karen a. veverka3 1spencer dermatology & skin surgery center, st. petersburg, fl; 2department of dermatology, university of nevada, las vegas, nv; 3leo pharma inc, madison, nj, usa introduction • actinic keratoses (aks) are epidermal lesions on the skin caused by damage from chronic exposure to uv rays from the sun and/or indoor tanning1 • aks have a risk of progressing to invasive squamous cell carcinoma (scc) if untreated; the majority of clinically diagnosed sccs originate from concomitant aks1 • ingenol mebutate (imb) (0.015% or 0.05%) gel is a topical ak treatment used to treat ak on the trunk and extremities, but it can elicit local skin reactions (lsrs) at the application site2-4 – lsrs are associated with erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration – managing lsrs during treatment of ak may be important for treatment adherence and setting patient expectations • previous clinical data have demonstrated that the treatment burden of lsrs associated with imb gel is minimal, manageable, and short lasting5 objective • to perform a systematic review of approaches used for managing or decreasing lsrs during treatment of ak with imb materials and methods • we systematically searched the electronic databases pubmed and medline to identify all relevant records through august 2019 • search terms included “ingenol mebutate,” “ambulatory care facilities,”“actinic keratosis,” “therapy,” and “lsr” – all relevant clinical studies in humans examining the clinical utility of imb were included – scientific review articles, as well as studies not published in english, were excluded – there were no limitations for date of publication • the literature search returned 49 results – titles, abstracts, and full text articles of the search results were screened for relevance – 6 studies were identified for in-depth analysis results • the 6 studies selected for the analysis represented a range of study designs (table 1) – retrospective chart reviews1,6,7 n=3 – randomized controlled trial8 n=1 – investigator-initiated single-blinded study9 n=1 – observational longitudinal cohort study10 n=1 • the 6 studies examined a total of 1437 patients; 1424 patients were evaluated for lsrs associated with imb • 3 of the studies only examined the resolution of lsrs over time in the absence of any intervention6,7,10 • the other studies evaluated different approaches in managing or minimizing lsrs during the treatment of ak – use of various topical moisturizers1,2,10 – implementing a low-dose regimen of imb6 – application of dimethicone9 – application of clobetasol propionate8 in-depth analysis of individual studies erlendsson am et al, 2016 • in a blinded, randomized controlled trial, erlendsson am et al, treated patients with multiple aks on the face and scalp with imb daily for 3 days8 • for each patient, 1 of 2 areas was randomized to receive topical clobetasol propionate (0.05%) twice daily for 4 days to treat lsrs, while the other area was left untreated • lsr rates in patients treated with imb were: – erythema (100%) – flaking (100%) – crusting (91%) • areas randomized to receive clobetasol propionate had no benefit over untreated areas in reducing lsrs and their associated pain and pruritis (figure 1) – by 2 weeks after treatment initiation, lsrs had returned to baseline both in areas treated with imb (0.67) and in areas treated with imb + clobetasol propionate (0.38; p=.250) jim on sc et al, 2017 • jim on sc, et al, studied 20 patients with multiple facial aks being treated with imb gel, 0.015%9 • 1% dimethicone lotion was applied once daily to 1 of 2 areas on the face containing 3-8 aks in an investigator-blinded manner • lsrs included the following and were graded on a scale from 0 (no reaction) to 4 (severe reaction) – erythema – flaking/scaling – swelling – vesiculation/pustulation – erosion/ulceration • dimethicone lotion with imb had no significant effect on lsr severity over treatment with imb alone (figure 2) figure 2. mean lsr scores in patients treated with imb vs imb + 1% dimethicone9 0 1 2 3 4 5 6 7 8 9 10 11 2 4 8 15 29 57 m ea n (± se ) l sr t ot al s co re day imb only imb + dimethicone se=standard error. figure 2 republished with permission of journal of drugs in dermatology from assessment of efficacy and irritation of ingenol mebutate gel 0.015% used with or without dimethicone lotion for treatment of actinic keratosis on the face, jim on sc, et al. j drugs dermatol. 2017; 16(5):432-436. neri l et al, 2017 • neri l et al, conducted an observational, multicenter, longitudinal cohort study in 1136 adult patients with multiple grade i/ii aks10 • lsrs were assessed at 2 follow-up visits: – t1: 8 days after initiation of ak treatment – t2: 25-30 days after initiation of ak treatment • approximately 37% of patients received treatment for lsrs at t1 – 53% received topical antibiotics – 47% received emollient creams • roughly 14% received treatment at t2 – 70% received emollient creams – 29% received antibiotics • there was a steep decrease in average lsr score (scale=0-4) from the first follow-up visit (2.6±1.5) to the second follow-up visit (0.9+1.0), which was seen in both lsr-treated and untreated groups bettencourt ms, 2016 • bettencourt ms conducted a study at a community dermatology practice in 78 male patients with recurring and relapsed scalp ak2 • all patients exhibited lsrs on the first day of treatment – erythema (100%) – flaking/scaling (97%) – crusting (66%) – swelling (6%) – vesiculation/pustulation (32%) – erosion/ulceration (13%) • 44% of the patients treated their lsrs with a topical product (figure 3) • lsrs were resolved in 10-14 days regardless of the use of a topical product – in 1 patient, lsrs were resolved at day 20 bettencourt ms, 2014 • bettencourt ms conducted a retrospective chart review of 135 patients who had a prolonged history of aks treated with imb7 • regardless of body area or use of lsr treatment, most patients had developed lsrs by day 2 of treatment (table 2) • most patients used no additional treatment for their lsrs – face: 83% used no treatment vs 17% used additional treatment – scalp: 85% used no treatment vs 15% used additional treatment – trunk/extremities: 92% used no treatment vs 8% used additional treatment bettencourt ms, 2014 (cont’d) table 2. lsr incidence and resolution by severity7 erythema flaking/scaling crusting resolution of lsrs without treatment mild moderate mild moderate mild moderate severe mild, moderate, & severe face (n=72) 72% 28% 75% 25% 19% 7% 1% 60/72 (83.3%) scalp (n=72) 73% 33% 34% 66% 7% 5% 0% 35/41 (85.4%) trunk/ extremities (n=24) 75% 4% 0% 8% 13% 4% 0% 22/24 (91.7%) • lsrs improved by 1 week after peak inflammation, despite being untreated in most patients7 • lsrs may resolve over time without the need for additional treatment joe hj et al, 2017 • joe hj et al, retrospectively evaluated patients with ak treated with normal (recommended-amount) or low-dose (low-amount) imb6 • recommended-amount group (rag) 18.8 mg/cm2 (n=20) • low-amount group (lag)a 10 mg/cm2 (n=27) • although the low-dose imb produced a significantly lower lsr score, the mean ak clearance rate in the rag was significantly greater than that of the lag – maximum composite lsr score, mean ± sd: 15.45 ± 2.70 in the rag vs 12.18 ± 3.29 in the lag, p<.001 – maximum pain score (vas), mean ± sd: 7.95 ± 0.99 in the rag vs 6.55 ± 1.42 in the lag, p<.001 – ak clearance rate, mean ± sd: 88.16 ± 12.30 in the rag vs 75.56 ± 9.44 in the lag, p<.001 – ak clearance rate (%), range: 66.67-100 in the rag vs 63.64-100 in the lag, p<.001 clearance rate = (the number of aks decreased after treatment/the number of aks before treatment) x 100 (%); p value, independent samples test. vas=visual analog scale; sd=standard deviation. adose used in the lag is lower than the approved labelling for imb. conclusions • topical application of imb gel in patients with ak elicits lsrs at the application site • based on available literature, lsrs in most patients treated with imb resolve spontaneously over time without the need for additional treatment – evidence is lacking to support a singular strategy for reducing or preventing imb-induced lsrs – studies evaluating the role of topical lotions, antibiotics, or moisturizers to treat lsrs found that these treatments provided no significant benefit in improving lsr severity over treatment with imb alone • after treatment with imb gel, 0.015% or 0.05%, lsrs only peak in intensity up to 1 week following treatment completion, and resolve spontaneously in 2-4 weeks without treatment3 – therefore, lsrs are unlikely to influence patients’ adherence behavior to imb – an understanding that lsrs typically resolve spontaneously over time may help manage patient expectations and improve patient satisfaction references 1. berman b, cohen de, amini s. what is the role of field-directed therapy in the treatment of actinic keratosis? part 1: overview and investigational topical agents. cutis. 2012;89(5):241-250. 2. bettencourt ms. tolerability of ingenol mebutate gel, 0.05%, for treating patients with actinic keratosis on the scalp in a community dermatology practice. j clin aesthet dermatol. 2016;9(3):20-24. 3. picato (ingenol mebutate) gel 0.015%, 0.05% [package insert]. madison, nj: leo pharma inc.; 2019. 4. lebwohl m, swanson n, anderson ll, et al. ingenol mebutate gel for actinic keratosis. n engl j med. 2012;366(11):1010-1019. 5. hanke wc, norlin jm, mark knudsen k, et al. quality of life in treatment of ak: treatment burden of ingenol mebutate gel is small and short lasting. j dermatolog treat. 2016;27(5):450-455. 6. joe hj, oh bh. ingenol mebutate in low amounts for the treatment of actinic keratosis in korean patients. clin cosmet investig dermatol. 2017;10:93-98. 7. bettencourt ms. use of ingenol mebutate gel for actinic keratosis in patients in a community dermatology practice. j drugs dermatol. 2014;13(3):269-273. 8. erlendsson am, karmisholt ke, haak cs, et al. topical corticosteroid has no influence on inflammation or efficacy after ingenol mebutate treatment of grade i to iii actinic keratoses (ak): a randomized clinical trial. j am acad dermatol. 2016;74(4):709-715. 9. jim on sc, hashim pw, nia jk, lebwohl mg. assessment of efficacy and irritation of ingenol mebutate gel 0.015% used with or without dimethicone lotion for treatment of actinic keratosis on the face. j drugs dermatol. 2017;16(5):432-436. 10. neri l, peris k, longo c, et al; actinic keratosis — treatment adherence initiative (ak-train) study group. physician-patient communication and patient-reported outcomes in the actinic keratosis treatment adherence initiative (ak-train): a multicenter, prospective, real-life study of treatment satisfaction, quality of life and adherence to topical field-directed therapy for the treatment of actinic keratosis in italy. j eur acad dermatol venereol. 2019;33(1):93-107. disclosures dr. freeman is an advisor and has received honoraria from foamix pharmaceuticals inc, castle biosciences, galderma usa, leo pharma inc and novartis; he participates in speaker bureaus and has received honoraria from foamix pharmaceuticals inc, leo pharma inc and novartis. dr. bettencourt is an advisor and has received honoraria from bristol myers squibb; she participates in speaker bureaus and has received honoraria from abbvie, almirall, celgene, leo pharma inc, ortho dermatologics, pfizer and sun pharmaceuticals. drs. ka veverka, n dunkelly-allen and m corliss are employees of leo pharma inc. funding this study was funded by leo pharma. acknowledgments editorial support funded by leo pharma inc was provided by p-value communications. poster no. 16258 reference study design number of patients in study number of patients evaluated for lsrs treatment for lsrs used conclusions 1 erlendsson am et al. j am acad dermatol. 2016;74(4):709-715. randomized controlled trial 21 21 clobetasol propionate, twice daily for 4 days, to one of 2 areas on the face or scalp patients randomized to receive clobetasol propionate had no benefit over untreated patients in reducing lsrs and their associated pain and pruritus 2 jim on sc. j drugs dermatol. 2017;16(5):432-436. investigator-initiated single-blinded study 20 20 1% dimethicone lotion, applied once daily to one of 2 areas on the face containing 3-8 aks dimethicone lotion with imb had no significant effect on lsr severity over treatment with imb alone 3 neri l et al. j eur acad dermatol venereol. 2019;33(1):93-107. observational longitudinal cohort study 1136 420 during first 8 days; 149 during follow-up follow-up 1 • emollient creams: 47% • topical antibiotics: 53% follow-up 2 • emollient creams: 70% • antibiotics: 29% there was a steep decrease in average lsr score (0-4) from the first follow-up visit (2.7±1.4) to the second follow-up visit (0.8±0.8), which was seen in both lsr-treated and untreated groups 4 bettencourt ms. j clin aesthet dermatol. 2016;9(3):20-24. retrospective chart review 78 65 34 of 78 treated their lsrs with: moisturizers (n=16) neosalus hydrating cream (n=9) skin barrier emollient cream (n=3) antipruritic hydrogel (n=3) petrolatum-based cream (n=2) dimethicone-based cream (n=2) anti-itch hydrogel (n=1) lsrs were resolved by 10-14 days in 98% of patients evaluated regardless of their use of moisturizers or emollients • in 1 patient, lsrs resolved by day 20 5 bettencourt ms. j drugs dermatol. 2014;13(3):269-273. retrospective chart review 135 total face (n=77) scalp (n=45) trunk (n=32) face (n=72) scalp (n=41) trunk (n=24) no treatment: 26% moisturizers & creams: 4% oral prednisone & tacrolimus 0.1%: 1 patient lsrs were cleared 1 week after peak inflammation in most patients, independent of treatment with moisturizers, creams, or oral prednisone and tacrolimus 6 joe hj, oh bh. clin cosmet investig dermatol. 2017;10:93-98. retrospective chart review 47 47 none below-recommended dosing of imb (10 mg/cm2) significantly reduced lsr score and pain score but was associated with a significantly lower ak clearance rate vs recommended dose imb (18.8 mg/cm2) presented at the 2020 american academy of dermatology, annual meeting, denver, colorado, march 20-24, 2020. table 1. profile of studies evaluating management of lsrs with the use of imb in treating ak dimethicone-based emollient cream [cerave – l’oréal group] 3% antipruritic hydrogel [exeltis usa] 4% skin barrier emollient cream [encore dermatology, inc.] 4% neosalus hydrating topical cream [quinnova pharmaceuticals llc] 12% anti-itch hydrogel [valeant pharmaceuticals international] 1% moisturizers 21% no treatment 56% petrolatum-based emollient cream [galderma laboratories] 3% figure 3. treatments used for lsrsfigure 1. development of lsrs in a patient treated with imb with or without clobetasol propionate – swelling (91%) – vesiculation (69%) – erosion (29%) skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 906 brief article a suspected case of imported yaws in new york mairead moloney, bs1, rebeca teplitz, do2, brian how, do2, suzanne sirota-rozenberg, do, faad, faocd2 1 new york institute of technology college of osteopathic medicine, old westbury, ny 2 st. john’s episcopal hospital, far rockaway, ny yaws is a non-venereal endemic treponematosis, which is morphologically and antigenically identical to venereal syphilis, caused by treponema pallidum, subspecies pallidum.1,2 yaws is caused by subspecies pertenue, and is characterized by chronic skin infections.3 yaws occurs in warm, humid, tropical climates, with an annual temperature of >27°c, and an annual rainfall of >1,300 mm/year.1,4 transmission occurs through direct skin-toskin contact with an infected lesion.3,4 risk factors include broken skin and injuries, such as bites and wounds.5-7 lesions are most commonly found on the lower extremities.2,3 a majority of cases (70-85%) occur in children under 15 years old.2 those affected abstract introduction: yaws is an endemic non-venereal treponematoses, which is caused by treponema pallidum, subspecies pertenue and is spread from person-to-person through direct skin contact with an infected lesion. yaws causes a chronic skin infection that is characterized by papillomas and ulcers and if left untreated can be disfiguring and debilitating. cases typically occur in warm, humid, tropical climates and cases are commonly seen in children under 15 years old. however, due to migration, cases can be seen outside of its endemic region. case description: we present a case of a 39-year-old african american male who presented with painless bilateral ulcers on his dorsal feet that began as blisters approximately 1-2 weeks prior to presentation at our clinic. our patient had recent travel history to jamaica and reported potential sources of trauma to his feet by walking barefoot on the beach and roofing in sandals prior to onset. these findings led to the clinical diagnosis of yaws. a regimen of azithromycin and basic wound care led to significant improvement. discussion: non-venereal endemic treponematoses, such as yaws, are typically not seen outside of their endemic region. however, due to migration and the ease of travel nonvenereal endemic treponematoses can be found elsewhere and it is important for healthcare workers to keep these diseases on their differential, especially in a patient with travel history. after making the diagnosis of yaws, proper treatment and basic wound care can result in rapid significant improvement and prevent the progression of yaws lesions to the subsequent stage. introduction skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 907 figure 1. progression of yaws lesions. figure 2. ulcerative plaque with a rolled border and amber-yellow crust on the patient’s right (a) and left (b) dorsal aspect of his foot and ankle in november 2022. photo taken one week after turning from jamaica and two weeks after initial onset. skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 908 figure 3. healing ulcerative plaque on patient’s right (a) and left (b) dorsal aspect of his foot and ankle in january 2023, approximately 9 weeks after initial presentation and after taking oral azithromycin and following a wound care regimen. are typically impacted by low socio-economic conditions, such as overcrowding and poor sanitation.4 lesions can progress through three stages (figure 1). the primary lesion, “mother yaw,” occurs at the site of inoculation typically within nine days to three months.1,2 it presents as an erythematous painless papule that enlarges peripherally, ulcerates, and develops an amber-yellow crust. ulcers are typically circular with a raised border and granulation tissue in the center.3 the primary lesion is rich in treponemes, which can disseminate through the bloodstream leading to secondary yaws. secondary yaws, “daughter yaws,” are smaller and more widespread than primary yaws.1 they occur close to body orifices and heal spontaneously over three to six months.1,3 both primary and secondary lesions are highly contagious.4 about 10% of individuals will progress to noncontagious tertiary yaws, in which, abscesses form, become necrotic, and ulcerate.1 the diagnosis of yaws is typically made clinically.1,3 the treponemes cannot be cultured on synthetic media.3 silver stains and dark-field microscopy can identify the spirochetes of endemic treponemes, but cannot differentiate between that of venereal syphilis.3 serologic testing also does not help differentiate between treponematoses.1,3 the current first-line treatment of yaws is a one-time oral dose of azithromycin (30 mg/kg, maximum 2g).1 for over 50 years, the first-line treatment was a single intramuscular benzathine penicillin injection.1 a benefit of azithromycin is that it can be easily skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 909 administered orally and can be given to those with a penicillin allergy.1 we report a case of suspected yaws in a new york patient who recently traveled to jamaica. a 39-year-old african american male with a past medical history of type 1 diabetes mellitus presented to the clinic in november 2022 with a chief complaint of painless ulcers on his bilateral dorsal feet. the ulcers started as blisters approximately 2 weeks prior, while he was in jamaica. he reported that before the blisters appeared, he frequently walked along the beach barefoot and was roofing wearing sandals. he saw a doctor when the blisters started to ulcerate and expand. he received a penicillin injection, a prescription of oral doxycycline 100mg twice daily for one week, and silver sulfadiazine cream applied daily. the patient denied any pain or systemic symptoms when he presented at our clinic. physical exam revealed large ulcerative plaques with rolled borders and without exudate on bilateral dorsal feet (figure 2). yaws, cutaneous leishmaniasis, and pyoderma gangrenosum (pg) were on the differential. a shave biopsy was taken from the patient’s left anterior ankle and an rpr blood test was ordered. the patient was prescribed a one-time dose of oral azithromycin 2g and daily application of silver sulfadiazine while keeping the ulcers wrapped. during his initial follow-up 4 days later, he reported significant improvement, which made yaws more likely than pg or leishmaniasis. the patient was instructed to continue the same wound care with the addition of daily saline soaks. he was then prescribed additional doses of azithromycin (250mg daily for 5 days) and was instructed to follow up in one week. the patient’s rpr returned negative and histopathological examination showed ulceration, granulation tissue and epidermal hyperplasia. the diagnosis of yaws was made clinically based on the patient’s history and rapid improvement with azithromycin. continuous improvement was seen at each follow-up visit (figure 3). broken skin and minor injuries are risk factors for yaws transmission which can occur in an individual of any age.7-12 our patient had a history of walking barefoot and roofing in sandals, which could have easily caused minor traumas to our patient’s feet/ankles. jamaica is a prime location with an ideal climate for yaws since it is located between the tropics. in the 1950s, jamaica was known to be an endemic country of yaws. after the world health organization’s (who) yaws eradication campaign, formal reporting of yaws stopped in many countries.4 jamaica currently falls into a group of countries previously known as endemic, with unknown current status.11 tropical treponematoses only occur in endemic countries, however, due to migration and travel, cases can be imported to non-endemic countries.3,7 one case of yaws was reported in the netherlands from a child who was infected with the disease in ghana.7 our patient most likely contracted yaws in jamaica and imported the disease to new york. therefore, it is important for healthcare providers to be aware that these treponematoses exist, as the disease can be easily missed.3,7 case report discussion skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 910 the diagnosis of yaws was made clinically in our patient based on lesion morphology, progression and history, although the who requires serologic positivity for case confirmation.4 the spirochetes are unable to be visualized on h&e. dark-field microscopy was not feasible and not completed. an rpr serologic test is a nonspecific nontreponemal antibody test that is typically positive in untreated cases.3 our patient had already been treated with a penicillin injection in jamaica by a doctor who also suspected yaws, which could explain the negative rpr. additionally, the antibody response in yaws is often not detected in the first 3 weeks of the infection.3 our patient received both treatment regimens for yaws, intramuscular penicillin and oral azithromycin. additional doses of oral azithromycin were prescribed due to the rapid clinical improvement noted four days after the initial dose. proper wound care is essential for patients with ulcerative lesions. rapid improvement was noted in our patient with daily saline soaks, silver sulfadiazine cream application, and having the ulcers wrapped. consistency with this wound care regimen and follow-up resulted in significant improvement. conflict of interest disclosures: none funding: none corresponding author: rebeca teplitz, do st. john’s episcopal hospital far rockaway, ny email: rebecateplitz@gmail.com references: 1. sommer ll, reboli ac, heymann wr. nonvenereal (endemic) treponematoses. in: dermatology. ; 2018:1259-1295. 2. world health organization. yaws. published 2023. accessed february 1, 2023. https://www.who.int/news-room/factsheets/detail/yaws 3. mitjà o, šmajs d, bassat q. advances in the diagnosis of endemic treponematoses: yaws, bejel, and pinta. plos negl trop dis. 2013;7(10). doi:10.1371/journal.pntd.0002283 4. kazadi wm, asiedu kb, agana n, mitjà o. epidemiology of yaws: an update. clin epidemiol. 2014;6(1):119-128. doi:10.2147/clep.s44553 5. world health organization. yaws (endemic treponematoses). accessed february 1, 2023. https://www.who.int/healthtopics/yaws#tab=tab_1 6. world health organization. global report on neglected tropical diseases 2023. published 2023. accessed february 5, 2023. https://www.who.int/teams/control-ofneglected-tropical-diseases/global-report-onneglected-tropical-diseases-2023 7. engelkens hjh, oranje ap, stolz e. early yaws, imported in the netherlands. genitourin med. 1989;65(5):316-318. doi:10.1136/sti.65.5.316 8. meteorological service division. our climate. accessed february 5, 2023. https://metservice.gov.jm/ourclimate/#:~:text=the island is surrounded by,florida and the panama canal. 9. ferguson ja, bryan p, buisseret dj, black c v. climate of jamaica. britannica. published 2022. accessed february 5, 2023. https://www.britannica.com/place/jamaica/cli mate 10. jamaica weather. met office. accessed february 5, 2023. https://www.metoffice.gov.uk/weather/travel/h oliday-weather/americas/caribbean/jamaicaweather 11. global health observatory data repository: status of endemicity for yaws data by country. world health organization. published 2022. accessed february 15, 2023. https://apps.who.int/gho/data/node.main.ntd yawsend?lang=en 12. boock au, awah pk, mou f, nichter m. yaws resurgence in bankim, cameroon: the relative effectiveness of different means of detection in rural communities. plos negl trop dis. 2017;11(5):1-14. doi:10.1371/journal.pntd.0005557 tapinarof cream for the treatment of plaque psoriasis: efficacy and safety by baseline disease characteristics and skin type in a phase 2b randomized study mark lebwohl md,1 james del rosso do,2 chih-ho hong md,3 anna m tallman pharmd,4 leon kircik md1,5 1icahn school of medicine at mount sinai, new york, ny, usa; 2jdr dermatology research/thomas dermatology, las vegas, nv, usa; 3university of british columbia and probity medical research, surrey, bc, canada; 4dermavant sciences, inc., long beach, ca, usa; 5skin sciences, pllc, louisville, ky, usa. introduction ■ psoriasis is a chronic, immune-mediated disease characterized by scaly, erythematous, and pruritic plaques that can be painful and disfiguring1 ■ although multiple options are available for the treatment of plaque psoriasis, there is a need for effective topical therapies that can be used without body surface area (bsa) restrictions or concerns for the duration of treatment ■ tapinarof cream is a therapeutic aryl hydrocarbon receptor modulating agent (tama) under investigation for the treatment of psoriasis (nct03956355 & nct03983980) and atopic dermatitis ■ this previously conducted phase 2b dose-finding study (nct02564042) was designed to assess the efficacy and safety of tapinarof cream in subjects with plaque psoriasis2,3 ■ factors related to disease characteristics and skin type may influence clinical outcomes in psoriasis4,5 ■ this post-hoc analysis was conducted to explore whether the efficacy and safety of tapinarof cream varied across subgroups by baseline disease characteristics and skin type objectives ■ to evaluate the efficacy and safety of tapinarof through post-hoc analysis of a phase 2b study in subjects with plaque psoriasis stratified by baseline disease characteristics, including % bsa affected, duration of psoriasis, and fitzpatrick skin type methods study design ■ in this multicenter (united states, canada, and japan), phase 2b, double-blind, vehicle-controlled, randomized study, adult subjects with psoriasis were randomized 1:1:1:1:1:1 to receive tapinarof cream 0.5% or 1% once (qd) or twice daily (bid) or vehicle qd or bid for 12 weeks and followed up for 4 more weeks (figure 1) figure 1. study design tapinarof 1% bid (n=38) tapinarof 1% qd (n=38) tapinarof 0.5% bid (n=38) tapinarof 0.5% qd (n=38) vehicle bid (n=37) vehicle qd (n=38) offtreatment adult subjects with stable plaque psoriasis for ≥6 months • aged 18–65 years • bsa ≥1%–≤15%* • pga ≥2 (n=227) r double-blind treatment (12 weeks) follow-up (4 weeks) *excluding scalp. bid, twice daily; bsa, body surface area; pga, physician global assessment; qd, once daily; r, randomized. study outcomes and statistical analysis ■ the primary endpoint was physician global assessment (pga) response rate at week 12, defined as the proportion of subjects with a pga score of clear (0) or almost clear (1) and ≥2-grade improvement in pga score from baseline to week 122 ■ additional post-hoc efficacy analyses reported here include pga response rates at week 12, stratified by the following baseline disease characteristics and skin type: – baseline % bsa affected: 1 to <10% and ≥10% – baseline duration of psoriasis: 6 months to <5 years, 5 years to <10 years, and ≥10 years – fitzpatrick skin type: fitzpatrick skin type i and ii, fitzpatrick skin type iii and iv, and fitzpatrick skin type v and vi ■ incidence, frequency, and nature of adverse events (aes) and serious aes were collected from the start of study treatment until the end-of-study visit at week 16 results subject characteristics ■ a total of 227 subjects (of the 290 subjects originally screened) were randomized (intent-to-treat population), and of those randomized, 175 subjects (77%) completed the study, including the week 16 follow-up visit ■ mean demographic and baseline characteristics were comparable across treatment groups (table 1) ■ overall, 15% of subjects had a baseline pga category of 2 (mild), 80% had a pga category of 3 (moderate), and 5% had a pga category of 4 (severe) ■ baseline mean psoriasis area and severity index score was 8.8 (standard deviation [sd] 4.5) table 1. baseline subject demographics and characteristics tapinarof cream 1% tapinarof cream 0.5% vehicle bid (n=38) qd (n=38) bid (n=38) qd (n=38) bid (n=37) qd (n=38) mean age, years (sd) 45.9 (11.9) 48.5 (10.6) 49.6 (10.9) 48.7 (9.7) 46.7 (12.6) 46.4 (10.2) male sex, n (%) 26 (68) 26 (68) 24 (63) 25 (66) 23 (62) 29 (76) mean weight, kg (sd) 85.6 (22.5) 86.7 (22.6) 88.6 (27.4) 89.3 (23.1) 87.8 (28.3) 91.6 (21.6) pga, mean (sd) 2.9 (0.4) 2.7 (0.5) 3.0 (0.5) 2.9 (0.4) 3.0 (0.3) 2.8 (0.4) pasi, mean (sd) 10.6 (5.0) 8.5 (3.6) 8.2 (4.5) 7.9 (4.8) 9.0 (4.3) 8.7 (4.4) % bsa affected, mean (sd) 8.2 (4.5) 6.5 (3.3) 7.2 (4.5) 6.1 (4.3) 6.6 (3.6) 7.0 (4.6) pruritus score, mean (sd)* 5.6 (2.6) 4.4 (2.9) 6.2 (2.2) 4.5 (2.6) 5.5 (2.8) 4.9 (2.4) mean duration of psoriasis, years (sd) 15.7 (14.1) 16.6 (12.9) 17.9 (14.1) 16.6 (13.3) 18.1 (15.0) 16.0 (12.4) fitzpatrick skin type i, n (%) 2 (6) 3 (9) 1 (3) 2 (6) 1 (3) 1 (3) fitzpatrick skin type ii, n (%) 8 (24) 7 (20) 10 (31) 6 (19) 5 (17) 13 (39) fitzpatrick skin type iii, n (%) 17 (50) 14 (40) 6 (19) 13 (41) 11 (37) 11 (33) fitzpatrick skin type iv, n (%) 2 (6) 7 (20) 7 (22) 7 (22) 7 (23) 5 (15) fitzpatrick skin type v, n (%) 5 (15) 3 (9) 5 (16) 4 (13) 5 (17) 3 (9) fitzpatrick skin type vi, n (%) 0 1 (3) 3 (9) 0 1 (3) 0 baseline disease characteristics provided for the mitt population (n=196), which included subjects in the itt population minus the subjects from one site due to protocol violation. demographics (age, sex, and weight) provided for the safety population (n=227). *mean scores based on an nrs of 0 ‘absent’ to 10 ‘worst imaginable’; data provided for subjects with available results (n=32, 35, 30, 32, 29, and 32, respectively). bid, twice daily; bsa, body surface area; itt, intent-to-treat; mitt, modified intent-to-treat; nrs, numeric rating scale; pasi, psoriasis area and severity index; pga, physician global assessment; qd, once daily; sd, standard deviation. pga response rates ■ primary endpoint: pga response rates (defined as pga score 0 or 1 and ≥2-grade improvement) at week 12 were significantly higher (at 0.05 significance level) in the tapinarof cream groups than the vehicle groups (65% [1% bid], 56% [1% qd], 46% [0.5% bid], 36% [0.5% qd] vs 11% [vehicle bid] and 5% [vehicle qd]) and were maintained for 4 weeks after the end-of-study treatment in all active treatment groups except for the 0.5% bid group2 pga response rates by baseline % bsa affected ■ pga response rates at week 12 were higher in tapinarof cream groups than vehicle groups, regardless of baseline % bsa affected (figure 2) – 1 to <10% bsa affected (n=102): 67% (1% bid), 60% (1% qd), 33% (0.5% bid), and 35% (0.5% qd) vs 13% (vehicle bid) and 6% (vehicle qd) – ≥10% bsa affected (n=39): 64% (1% bid), 40% (1% qd), 75% (0.5% bid), and 38% (0.5% qd) vs 0% (vehicle bid) and 0% (vehicle qd) figure 2. proportion of subjects who achieved pga response* at week 12 by % bsa affected at baseline 38 n=8 75 n=8 40 n=5 64 n=11 6 n=17 13 n=15 35 n=20 33 n=18 60 n=20 67 n=12 p ro p o rt io n o f su b je ct s, % bsa affected, % 60 80 100 40 20 0 1% to <10% ≥10% tapinarof 1% bid tapinarof 1% qd tapinarof 0.5% bid tapinarof 0.5% qd vehicle bid vehicle qd n=4 0 0 n=3 n is number of subjects with available results at week 12. *defined as pga score 0 or 1 and ≥2-grade improvement from baseline. bid, twice daily; bsa, body surface area; pga, physician global assessment, qd, once daily. pga response rates by baseline duration of psoriasis ■ pga response rates at week 12 were higher in tapinarof cream groups than in vehicle groups, regardless of baseline duration of psoriasis, except for the 0.5% bid treatment group in the 5 years to <10 years subgroup (figure 3) – 6 months to <5 years (n=27): 50% (1% bid), 80% (1% qd), 50% (0.5% bid), and 29% (0.5% qd) vs 0% (vehicle bid) and 0% (vehicle qd) – 5 years to <10 years (n=32): 67% (1% bid), 50% (1% qd), 20% (0.5% bid), and 50% (0.5% qd) vs 25% (vehicle bid) and 0% (vehicle qd) – ≥10 years (n=82): 73% (1% bid), 50% (1% qd), 53% (0.5% bid), and 33% (0.5% qd) vs 8% (vehicle bid) and 8% (vehicle qd) figure 3. proportion of subjects who achieved pga response* at week 12 by duration of psoriasis at baseline p ro p o rt io n o f su b je ct s, % duration of psoriasis 60 80 100 40 20 0 6 months to <5 years 5 years to <10 years ≥10 years 50 80 50 29 0 0 n=6 n=5 n=4 n=7 n=3 n=2 0 67 50 20 50 25 n=6 n=6 n=5 n=6 n=4 n=5 73 50 53 33 8 8 n=11 n=14 n=17 n=15 n=12 n=13 tapinarof 1% bid tapinarof 1% qd tapinarof 0.5% bid tapinarof 0.5% qd vehicle bid vehicle qd n is number of subjects with available results at week 12. *defined as pga score 0 or 1 and ≥2-grade improvement from baseline. bid, twice daily; pga, physician global assessment, qd, once daily. pga response rates by fitzpatrick skin type ■ pga response rates at week 12 were higher in tapinarof cream groups than vehicle groups, regardless of fitzpatrick skin type (figure 4) – fitzpatrick skin type i/ii (n= 41): 60% (1% bid), 67% (1% qd), 50% (0.5% bid), and 25% (0.5% qd)vs 0% (vehicle bid) and 10% (vehicle qd) – fitzpatrick skin type iii/iv (n=73): 54% (1% bid), 47% (1% qd), 60% (0.5% bid), and 44% (0.5% qd) vs 18% (vehicle bid) and 0% (vehicle qd) – fitzpatrick skin type v/vi (n=27): 100% (1% bid), 75% (1% qd), 25% (0.5% bid), and 25% (0.5% qd) vs 0% (vehicle bid) and 0% (vehicle qd) figure 4. proportion of subjects who achieved pga response* at week 12 by fitzpatrick skin type p ro p o rt io n o f su b je ct s, % fitzpatrick skin type 60 80 100 40 20 0 tapinarof 1% bid tapinarof 1% qd tapinarof 0.5% bid tapinarof 0.5% qd vehicle bid vehicle qd 60 67 50 25 0 10 i/ii n=5 n=6 n=8 n=8 n=4 n=10 0 iii/iv 54 47 60 44 18 n=13 n=15 n=10 n=16 n=11 n=8 v/vi 100 75 25 25 0 0 n=5 n=4 n=8 n=4 n=4 n=2 n is number of subjects with available results at week 12. *defined as pga score 0 or 1 and ≥2-grade improvement from baseline. bid, twice daily; pga, physician global assessment, qd, once daily. safety ■ treatment-emergent aes (teaes) were mostly mild to moderate in severity ■ the most common treatment-related teaes were folliculitis (10% tapinarof vs 1% vehicle), contact dermatitis (3%; all tapinarof), and headache (1%; all tapinarof) ■ incidence and type of aes were generally comparable across subgroups and consistent with those observed in the overall population conclusions ■ overall, tapinarof cream was efficacious and well tolerated regardless of baseline % bsa affected, psoriasis duration, and fitzpatrick skin type ■ higher pga response rates at week 12 were observed in the tapinarof cream 1% qd group vs vehicle across all subgroups ■ these findings support the previously reported efficacy and safety outcomes of the overall population2,3 ■ a phase 3 clinical trial program of tapinarof cream 1% qd in psoriasis, consisting of two studies psoaring 1 (nct03956355) and psoaring 2 (nct03983980) has completed. the long-term extension study psoaring 3 (nct04053387) is ongoing references 1. menter a et al. j am acad dermatol. 2008;58:829–850; 2. robbins k et al. j am acad dermatol. 2019;80:714–721; 3. stein gold l et al. j am acad dermatol. 2020. doi: 10.1016/j.jaad.2020.04.181; 4. gisondi p et al. int j mol sci. 2017;18:2427; 5. alexi af, blackcloud p. j clin aesthet dermatol. 2014;7:16–24. acknowledgments the authors thank the participating investigators, patients and their families, and colleagues involved in the conduct of the study. editorial and medical writing support under the guidance of the authors was provided by apothecom, uk, and was funded by dermavant sciences, inc. in accordance with good publication practice (gpp3) guidelines (ann intern med. 2015;163:461–464). skin july 2019 volume 3 issue 4 copyright 2019 the national society for cutaneous medicine 266 brief articles lepromatous leprosy: an elusive mimicker mistaken for polyarteritis nodosa and disseminated tuberculosis danielle fasciano, do1, matthew innes, md2, david dorn, md1, david ullman, md1 , elizabeth ergen, md2, vishnu reddy, md1 , peter pavlidakey, md1, 2. 1department of pathology and laboratory medicine, university of alabama at birmingham, birmingham, al 2department of dermatology, university of alabama at birmingham, birmingham, al leprosy or hansen’s disease refers to an infection caused by the obligate-intracellular organism mycobacterium leprae or less commonly mycobacterium lepromatosis. it affects fewer than 250 individuals in the united states per year (1), although epidemiologic data is based on voluntary reporting and likely underestimates its true incidence. most cases occur in immigrants from other countries. the average incubation time is 5 years. it primarily affects the skin, peripheral nerves, upper respiratory tract, eyes and reticuloendothelial system (1). clinically, the disease may initially present as hypopigmented macules, sometimes mistaken for tinea versicolor or vitiligo. the ridley-jopling classification system classifies cases along a spectrum with a tuberculoid leprosy is a chronic infectious disease caused by the obligate intracellular microorganism, mycobacterium leprae and presents as skin lesions and peripheral neuropathies with upper respiratory mucosa involvement. we present a case of a 36-year-old immunocompromised female whom was recently diagnosed polyarteritis nodosa vasculitis (pan) in trinidad and returned back to the us with a two-week history of pleuritic chest pain, fever, chills, fatigue, nausea, vomiting, epistaxis and cough. physical examination revealed a diffuse rash. pancytopenia prompted a bone marrow biopsy, which revealed acid-fast bacteria, suspicious for disseminated tuberculosis. histologic examination of the skin lesions revealed disseminated acid-fast, fite-positive microorganisms within the dermis and nerves. she developed anuric renal failure and purpura fulminans with disseminated intravascular coagulation (dic). pcr results from the skin sample shortly thereafter revealed the presence of m. leprae dna. mycobacterium tuberculosis complex dna was not identified. this case demonstrates an unusual presentation of leprosy with bone marrow involvement and highlights the importance of utilizing histologic examination together with molecular diagnostic techniques to aid in establishing the correct diagnosis and treatment. this case also cautions that leprosy can be misdiagnosed as a vasculitis, specifically pan, as there is overlap in the clinical presentation of each disease and that clinicopathologic correlation is essential. abstract introduction skin july 2019 volume 3 issue 4 copyright 2019 the national society for cutaneous medicine 267 pole and a lepromatous pole (tuberculoid, borderline tuberculoid, mid-borderline, borderline lepromatous, lepromatous and indeterminate) depending on the integrity of the individual’s immune response (2). the tuberculoid pole is characterized by a robust host immune response with few organisms and typical clinical findings of one to three hypopigmented, hypoesthetic, welldemarcated patches. the lepromatous pole is typified by an ineffective host immune response with numerous organisms and widely distributed, raised skin lesions forming coalescing plaques (2). histologically, the disease is diverse on a spectrum and may demonstrate dermal granulomas with or without abundant langerhans cells, lymphocytes and foamy macrophages with blue-gray cytoplasm; however, clinicopathological correlation is essential for properly assigning a specific diagnosis among the various clinical forms of the disease. leprosy is a curable disease with treatment consisting of a multidrug regimen administered for 24-months with the aim of preventing resistance and relapse. a combination of dapsone and rifampin is generally used for tuberculoid leprosy with clofazamine added for lepromatous disease (1, 10). a 36-year-old woman from trinidad and tobago presented with localized skin nodules on the right foot and leg, lower extremity paresthesia, progressive difficulty walking, fatigue and low-grade fevers. she was diagnosed with polyarteritis nodosa (pan) by her doctor in trinidad and tobago and initiated on prednisone (1 mg/kg, tapered over months). four months later, azathioprine was added for persistent fever, malaise and skin lesions. three weeks later, after returning to the u.s., she presented with fever, chills, fatigue, nausea, vomiting, epistaxis and cough. examination revealed numerous erythematous-violaceous papules on the trunk and extremities as well as livedoid erythema of the lower extremities (figure 1). labs were notable for pancytopenia: wbc of 3.0 x 109/l (absolute neutrophil count of 0), platelets of 80 x 109/l and a hemoglobin of 8.3 g/dl. blood cultures were positive for streptococcus mitas/oralis. a t2 candida antigen was positive, consistent with candida fungemia. a bone marrow biopsy revealed hypocellular marrow with abundant foamy macrophages and acid-fast bacilli (figure 2). treatment was initiated for presumed tuberculosis with rifampin 600 mg/d, isoniazid 300mg/d, pyrazinamide 1500 mg/d and ethambutol 1370 mg/d (ripe) in addition to piperacillin/tazobactam and amphotericin b for treatment of bacterial and fungal sepsis. a skin biopsy of the lesions revealed abundant acid-fast, fite-positive bacilli throughout the dermis and within nerves, foamy macrophages with blue-grey cytoplasm as well as an extensive thrombotic vasculopathy (figure 3). the patient developed anuric renal failure, purpura fulminans and disseminated intravascular coagulation (dic) and died within 2 weeks of presentation and initiation of ripe therapy. a skin biopsy sent for pcr revealed mycobacterium leprae dna. mycobacterium tuberculosis complex dna was not identified. figure 1. skin examination revealed livedoid erythema of the bilateral lower extremities (a) and widely scattered annular, raised, 0.5-2 cm, dusky, erythematous-violaceous papules on the trunk and extremities (b) case report skin july 2019 volume 3 issue 4 copyright 2019 the national society for cutaneous medicine 268 figure 2. bone marrow biopsy (20x) showing markedly hypocellular marrow with abundant foamy macrophages (a). additional afb stain (100x) demonstrates rare acid-fast bacilli within the bone marrow (b). figure 3. skin biopsy of lesion (4x) showing abundant foamy macrophages within the dermis and subcutaneous tissue (a). foamy macrophages with blue-grey cytoplasm (20x) surrounding adnexal structures (b). accompanying fite stain (100x) demonstrating numerous positive staining microorganisms within macrophages in dermis (c). leprosy should be considered in the differential of skin lesions on the extremities, especially those occurring on the hands and discussion skin july 2019 volume 3 issue 4 copyright 2019 the national society for cutaneous medicine 269 feet with associated sensory loss. in the united states, most cases are acquired abroad, so foreign birth or a history of international travel increase the probability of the diagnosis (2). in this case, the patients presenting symptoms were attributed to pan. other authors have cautioned about leprosy being misdiagnosed as a vasculitis, specifically pan (3, 4). both diseases can present with nodules on the skin of the lower legs with associated numbness and weakness (in the case of pan this is due to mononeuritis multiplex). a biopsy generally allows for a clear distinction. this avoidable error has important consequences as immunosuppressive therapy further impairs the host response to m. leprae and may lead to a worse prognosis. m. tuberculosis and mycobacterium avium complex are more frequently encountered in bone marrow biopsies than m. leprae. all of these organisms are acid-fast and paspositive (6). a fite stain should routinely be done as it has higher specificity in the skin and helps to avoid missing this diagnosis. in this case, the patient was initially presumed to have disseminated tuberculosis based on a positive acid-fast stain in the bone marrow. because bone marrow evaluation is not routinely done in leprosy care (6) the frequency of bone marrow involvement is unknown. the histologic features have been described in case series (8, 9). pancytopenia has been reported (6, 10) in association with bone marrow involvement. the pancytopenia observed in this case may have been due to lepromatous infiltration of bone marrow, azathioprine toxicity or sepsis. catastrophic immunologic reactions may occur in the course of leprosy, bacterial and fungal sepsis or as a consequence of initiation of rifampin for disseminated mycobacterial disease (11, 12). in this case, the patient developed dic and purpura fulminans within 11 days of diagnosis, despite treatment for disseminated mycobacterial, fungal and bacterial infections. while her labs later in the admission supported the diagnosis of dic (including elevated pt/ptt and d-dimer), we also considered the possibility of lucio phenomenon to explain the livedoid erythema on her legs that we noted on our initial examination. in summary, this case highlights the importance of combining clinical presentation and histologic examination with further ancillary testing including appropriate immunohistochemistry and molecular testing to aid in a definitive diagnosis and subsequent proper treatment. this case further demonstrates the importance of considering an infectious disease such as leprosy in the clinical setting of cutaneous vasculitis such as pan or autoimmune disease and under immunosuppressive therapy. skin july 2019 volume 3 issue 4 copyright 2019 the national society for cutaneous medicine 270 conflict of interest disclosures: none. funding: none. corresponding author: danielle fasciano university of alabama at birmingham, department of pathology, south, birmingham, al dfasciano@uabmc.edu references: 1. hansen's disease (leprosy). centers for disease control and prevention. last updated: 2017 feb 10. accessed: 2018 oct 11. retrieved from: https://www.cdc.gov/leprosy/index.ht ml. 2. pardillo f, fajardo t, abalos r, scollard d, gelber r. methods for the classification of leprosy for treatment purposes. clinical infectious diseases. 2007; 44(8): 1096 3. national hansen's disease (leprosy) program caring and curing since 1894. health resources and services administration. last updated: 2018 may 1. accessed: 2018 oct 11. retrieved from: https://www.hrsa.gov/hansensdisease/index.html. 4. powell s, mcdougall c. clinical recognition of leprosy: some factors leading to delays in diagnosis. british medical journal. 1974; 1(5908): 612. 5. misra dp, parida jr, chowdhury ac, et al. lepra reaction with lucio phenomenon mimicking cutaneous vasculitis. case reports in immunology. 2014; 2014: 641989. 6. naidoo s, naicker vl. a demonstration of the similiarities and differences in bone marrow morphology with nontuberculous mycobacterial infections. international journal of laboratory hematology. 2015; 37(2): e19. 7. somanath p, vijay kc. bone marrow evaluation in leprosy: clinical implications. leprosy review. 2016; 87(1): 122. 8. singh n, bhatia a, lakra a, arora vk, bhattacharya sn. comparative cytomorphology of skin, lymph node, liver and bone marrow in patients with lepromatous leprosy. cytopathology : official journal of the british society for clinical cytology. 2006; 17(5): 257. 9. sen r, sehgal pk, dixit v, et al. lipidladen macrophages in bone marrow of leprosy patients. leprosy review. 1991; 62(4): 374. 10. binitha mp, saritha s, riyaz n, mary v. pancytopenia due to lepromatous involvement of the bone marrow: successful treatment with multidrug therapy. leprosy review. 2013; 84(2): 145. 11. havey tc, cserti-gazdewich c, sholzberg m, keystone js, gold wl. recurrent disseminated intravascular coagulation caused by intermittent dosing of rifampin. the american journal of tropical medicine and hygiene. 2012; 86(2): 264. 12. chen g, he jq. rifampicin-induced disseminated intravascular coagulation in pulmonary tuberculosis treatment: a case report and literature review. medicine. 2017; 96(7): e6135. file:///c:/users/vladimir%20prado/appdata/local/temp/temp1_archive.zip/dfasciano@uabmc.edu patient concerns and treatment satisfaction in patients treated with azelaic acid foam for rosacea williamson t1; cameron j1; mcleod k2; turner b2; quillen a2; larose a1 bayer healthcare pharmaceuticals inc., whippany, nj, usa; 2xcenda, palm harbor, fl, usa sponsorship: this research was sponsored by bayer healthcare pharmaceuticals.presented at the 2018 winter clinical dermatology conference, january 12-17, 2018; lahaina, hawaii synopsis • rosacea is a common, chronic, inflammatory skin disorder affecting the convexities of the central face and can be categorized into 4 main subtypes: erythematotelangiectatic, papulopustular, phymatous, and ocular.1,2 • regardless of subtype, non-pharmacologic or behavioral interventions are useful for the management of skin flares; however, for patients with mild to moderate cases, especially of papulopustular rosacea, topical therapies are usually used as first-line therapy.1,3 • the use of topical medications, including metronidazole and azelaic acid gel, has shown efficacy in clinical trials vs placebo in reducing inflammatory lesion counts in patients with papulopustular rosacea; however, these treatments were associated with higher incidences of post-application skin discomfort, as patients reported burning, itching, and stinging sensations.1,2,4-6 • formulations like azelaic acid foam have the potential to offer improvements over the side effect profiles of these treatment options. objective • this study aimed to survey patients with rosacea about their concerns, treatment satisfaction, and quality of life (qol) associated with their azelaic acid foam treatment. methods study design • the study utilized a non-interventional, prospective, observational design and enrolled participants via email in collaboration with a patient support program, the rosacea concierge program. • a cross-sectional design was used to assess key patient concerns, treatment satisfaction, and qol related to azelaic acid foam for rosacea. sample selection • 2,150 patients from the united states (us) who were enrolled in the rosacea concierge program were invited to participate in the study. • all inclusion and exclusion criteria were patient reported. • inclusion criteria: − at least 18 years of age − diagnosis of rosacea by a medical professional − currently using azelaic acid foam as topical monotherapy for rosacea − willing and able to provide voluntary, informed consent to participate in the study • exclusion criteria: − use of any other topical treatment for rosacea at the time of enrollment study endpoints • eligible, consenting patients completed a 1-time survey assessing demographics, clinical characteristics (ie, rosacea-relevant comorbidities and complications), treatment history, and adverse events. • table 1 includes a brief overview of the 3 questionnaires included in the survey. figure 2. patient concerns with rosacea treatment 74.1% 11.1% 5.6% 5.6% 5.6% 5.6% 1.9% 2.0% 2.0% 2.0% 0.0% 0.0% 0.0% 0.0% 0% 20% 40% 60% 80% 100% none cost efficacy application dryness residue left on face sun sensitivity itching scarring burning smell soreness stinging texture % o f r e sp o n d e n ts r e p o rt in g c o n ce rn concern limitations • due to the limited respondent pool, further research is needed to confirm these results. − the international society of pharmacoeconomics and outcomes research (ispor) recommends that a minimum sample size of 200 patients is needed to obtain meaningful survey results in research on patient-reported outcomes. a total of 2,150 patients were invited to participate in this study, and 150 responded; however, only 54 met eligibility criteria and were enrolled in the study. conclusion • azelaic acid foam was well tolerated and efficacious, with less than 26% of participants reporting any concerns or side effects and 6% reporting a concern with treatment efficacy. • azelaic acid foam users reported favorable results in the domains of burning, itching, and stinging. • due to the limited respondent pool, further research is needed to confirm these results. references 1. webster gf. rosacea. med clin north am. 2009;93(6):1183-1194. 2. powell fc. clinical practice. rosacea. n engl j med. 352(8):793-803. 3. van zuuren ej, kramer s, carter b, graber ma, fedorowicz z. interventions for rosacea. cochrane database syst rev. 2011;(3):cd003262. 4. culp b, scheinfeld n. rosacea: a review. p&t. 2009;34(1):38-45. 5. berg m, liden s. an epidemiological study of rosacea. acta dermatol venereol. 1989;69:419-423. 6. wilkin j, dahl m, detmar m, et al. standard classification of rosacea: report of the national rosacea society expert committee on the classification and staging of rosacea. j am acad dermatol. 2002;(4):584-587. table 2. baseline characteristics and rosacea-relevant medical conditions total, n=54 gender, n (%) female 49 90.7 male 5 9.3 age (years) mean (standard deviation) 48.1 (9.4) min 26.0 median 48.5 max 63.0 health insurance coverage type, n (%) preferred provider organization 41 75.9 health maintenance organization 8 14.8 worker’s compensation/motor vehicle/third-party liability 0 0.0 medicaid 2 3.7 medicare/medicare supplemental 0 0.0 indemnity 0 0.0 other 5 9.3 rosacea-relevant medical conditions, n (%) none 42 77.8 depression 5 9.3 migraine 5 9.3 conjunctivitis 4 7.4 blepharitis 1 1.9 corneal neovascularization/keratitis 0 0 patient attrition • study recruitment and patient attrition are summarized in figure 1. • 2,150 program-identified patients were invited to participate, 150 patients responded, and 54 met all eligibility criteria and were included in the study. results figure 1. study recruitment and patient attrition patients invited to participate in the study (n=2,150) eligible patients included in the study (n=54) patients responding to the invitation (n=150) ineligible not using azelaic acid foam as monotherapy (n=50, 36.0%) • incomplete survey (n=43, 28.7%)• no diagnosis of rosacea by a medical professional (n=2, 1.3%) • repeat survey responses (n=1, 0.7%) • figure 6. mean satmed-q scores 58.4 2.5 70.8 76.1 51.7 75.9 79.0 0 20 40 60 80 100 satmed-q score undesirable side effects treatment effectiveness convenience of use impact on daily activities medical care global satisfaction m e a n s co re satmed-q category key: satmed-q – satisfaction with medicines questionnaire. demographics • a total of 54 patients were included in the study. patient population characteristics and rosacea medical history are described in table 2. • participants were primarily female (90.7%), ranging in age from 26 to 63 years. • the majority of participants (77.8%) reported no rosacea-relevant medical conditions. • the most common subtypes reported by study participants were erythematotelangiectatic and papulopustular (74.1% each), with 59.3% of participants reporting “mild” rosacea symptoms (16.7% “absent”; 24.1% “moderate”) in the 4 weeks before enrollment. • only 13.0% of patients reported no previous rosacea treatment. figure 3. rosacea treatment concerns’ mean importance scores cost efficacy application dryness residue sun sensitivity itching scarring burning smell soreness stinging texture 9.3 10.0 9.0 8.0 6.3 10.0 8.0 8.0 3.0 0.0 0.0 0.0 0.0 0 2 4 6 8 10 m e a n i m p o rt a n ce s co re o f c o n ce rn concern figure 4. side effects with rosacea treatment none dryness stinging itching redness/worsening of rosacea burning residue left on face soreness uneven skin tone side effect 77.8% 13.0% 7.4% 5.6% 5.6% 3.7% 1.9% 0.0% 0.0% 0% 20% 40% 60% 80% 100% % o f r e sp o n d e n ts r e p o rt in g s id e e ff e ct figure 5. mean importance scores of rosacea treatment side effects 5.3 2.5 4.7 8.3 7.0 2.0 0.0 0.0 0 2 4 6 8 10 dryness stinging itching redness/worsening of rosacea burning residue left on face soreness uneven skin tone m e a n i m p o rt a n ce s co re o f s id e e ff e ct side effect treatment satisfaction and qol • the global satisfaction (satmed-q) mean score was 79.0 and treatment effectiveness mean score was 70.8 (figure 6). standardized scores for the satmed-q ranged from 0 to 100, with an overall score of 59.3 indicating feeling neutral and each additional 13.4-point increase indicating a clinically meaningful movement toward satisfaction. • the impact of rosacea on qol was “minimal” (mean dlqi score: 2.35). dlqi scores ranged from 0 to 30 (with 0–1 indicating rosacea has no effect on qol and 21–30 indicating rosacea has an extremely large effect on qol). exploratory analysis • in regression models used for the exploratory analysis, increasing dryness importance scores were significantly associated with worsening treatment satisfaction and qol in satmed-q and dlqi. • the most commonly reported topical agent for prior rosacea treatment was metronidazole gel (7.4%). patient concerns • the majority of patients reported no concerns (74.1%) with their treatment (figure 2). the biggest concern reported was cost (11.1% of patients), with a mean importance score (is) on a 10-point scale of 9.3 (figure 3). table 1. questionnaires included in the patient survey questionnaire details rosacea treatment preference questionnaire • 9-question survey composed of both aided and unaided questions. • assesses patient self-reported rosacea subtype and severity and evaluates drug characteristics that contribute to patient satisfaction/dissatisfaction and treatment decisions with rosacea topical treatments. • respondents list up to 5 concerns as well as up to 5 side effects with their current topical rosacea treatment experienced in the past 4 weeks and rate the importance of each reported concern or side effect. • respondents rank a list of pre-identified issues with topical rosacea treatment (eg, efficacy, cost, texture, dryness, etc) on a scale of importance from 0 to 10 (with 0 = not at all important; 10 = extremely important) in terms of how important the issue is when they consider using a new topical rosacea treatment. satmed-q • 17-question, validated, multidimensional, generic questionnaire designed for use in patients with any chronic disease treated with medicines measuring treatment satisfaction. • composed of 6 domains: − undesirable side effects (3 questions) − efficacy (3 questions) − convenience and ease of use (3 questions) − impact of medicine (3 questions) − medical follow-up/review (2 questions) − overall opinion (3 questions) dlqi • 10-question, widely used dermatology-related qol tool. • questions are general and cover symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment experience over the previous week. key: dlqi – dermatology life quality index; qol – quality of life; satmed-q – satisfaction with medicines questionnaire. statistical analysis • all study analyses conducted were exploratory and descriptive in nature. • the primary analysis population set included all patients who met the eligibility criteria and completed the survey. − baseline characteristics were calculated as mean values for continuous variables and percentages for categorical variables. − proportions of patients listing each concern or side effect related to azelaic acid foam in the rosacea treatment preference questionnaire were assessed. − all the importance or tolerability scores that patients assigned to each concern or side effect, the satisfaction score from the satisfaction with medicines questionnaire (satmed-q), and the qol score from the dermatology life quality index (dlqi) were computed and summarized using means standard deviations and medians as appropriate. • as an exploratory analysis to assess the association between concerns and side effects vs overall treatment satisfaction and overall qol, regression analyses were conducted. • a majority (77.8%) of patients reported no side effects (figure 4). dryness was the most commonly reported side effect (13.0%; is: 5.3). other side effects reported included stinging (7.4%, is: 2.5), itching (5.6%; is: 4.7), redness (5.6%; is: 8.3), and burning (3.7%; is: 7.0) (figure 5). patient concerns and treatment satisfaction in patients treated with azelaic acid foam for rosacea williamson t1; cameron j1; mcleod k2; turner b2; quillen a2; larose a1 bayer healthcare pharmaceuticals inc., whippany, nj, usa; 2xcenda, palm harbor, fl, usa continue >> patient concerns and treatment satisfaction in patients treated with azelaic acid foam for rosacea williamson t1; cameron j1; mcleod k2; turner b2; quillen a2; larose a1 bayer healthcare pharmaceuticals inc., whippany, nj, usa; 2xcenda, palm harbor, fl, usa sponsorship: this research was sponsored by bayer healthcare pharmaceuticals.presented at the 2018 winter clinical dermatology conference, january 12-17, 2018; lahaina, hawaii synopsis • rosacea is a common, chronic, inflammatory skin disorder affecting the convexities of the central face and can be categorized into 4 main subtypes: erythematotelangiectatic, papulopustular, phymatous, and ocular.1,2 • regardless of subtype, non-pharmacologic or behavioral interventions are useful for the management of skin flares; however, for patients with mild to moderate cases, especially of papulopustular rosacea, topical therapies are usually used as first-line therapy.1,3 • the use of topical medications, including metronidazole and azelaic acid gel, has shown efficacy in clinical trials vs placebo in reducing inflammatory lesion counts in patients with papulopustular rosacea; however, these treatments were associated with higher incidences of post-application skin discomfort, as patients reported burning, itching, and stinging sensations.1,2,4-6 • formulations like azelaic acid foam have the potential to offer improvements over the side effect profiles of these treatment options. objective • this study aimed to survey patients with rosacea about their concerns, treatment satisfaction, and quality of life (qol) associated with their azelaic acid foam treatment. methods study design • the study utilized a non-interventional, prospective, observational design and enrolled participants via email in collaboration with a patient support program, the rosacea concierge program. • a cross-sectional design was used to assess key patient concerns, treatment satisfaction, and qol related to azelaic acid foam for rosacea. sample selection • 2,150 patients from the united states (us) who were enrolled in the rosacea concierge program were invited to participate in the study. • all inclusion and exclusion criteria were patient reported. • inclusion criteria: − at least 18 years of age − diagnosis of rosacea by a medical professional − currently using azelaic acid foam as topical monotherapy for rosacea − willing and able to provide voluntary, informed consent to participate in the study • exclusion criteria: − use of any other topical treatment for rosacea at the time of enrollment study endpoints • eligible, consenting patients completed a 1-time survey assessing demographics, clinical characteristics (ie, rosacea-relevant comorbidities and complications), treatment history, and adverse events. • table 1 includes a brief overview of the 3 questionnaires included in the survey. figure 2. patient concerns with rosacea treatment 74.1% 11.1% 5.6% 5.6% 5.6% 5.6% 1.9% 2.0% 2.0% 2.0% 0.0% 0.0% 0.0% 0.0% 0% 20% 40% 60% 80% 100% none cost efficacy application dryness residue left on face sun sensitivity itching scarring burning smell soreness stinging texture % o f r e sp o n d e n ts r e p o rt in g c o n ce rn concern limitations • due to the limited respondent pool, further research is needed to confirm these results. − the international society of pharmacoeconomics and outcomes research (ispor) recommends that a minimum sample size of 200 patients is needed to obtain meaningful survey results in research on patient-reported outcomes. a total of 2,150 patients were invited to participate in this study, and 150 responded; however, only 54 met eligibility criteria and were enrolled in the study. conclusion • azelaic acid foam was well tolerated and efficacious, with less than 26% of participants reporting any concerns or side effects and 6% reporting a concern with treatment efficacy. • azelaic acid foam users reported favorable results in the domains of burning, itching, and stinging. • due to the limited respondent pool, further research is needed to confirm these results. references 1. webster gf. rosacea. med clin north am. 2009;93(6):1183-1194. 2. powell fc. clinical practice. rosacea. n engl j med. 352(8):793-803. 3. van zuuren ej, kramer s, carter b, graber ma, fedorowicz z. interventions for rosacea. cochrane database syst rev. 2011;(3):cd003262. 4. culp b, scheinfeld n. rosacea: a review. p&t. 2009;34(1):38-45. 5. berg m, liden s. an epidemiological study of rosacea. acta dermatol venereol. 1989;69:419-423. 6. wilkin j, dahl m, detmar m, et al. standard classification of rosacea: report of the national rosacea society expert committee on the classification and staging of rosacea. j am acad dermatol. 2002;(4):584-587. table 2. baseline characteristics and rosacea-relevant medical conditions total, n=54 gender, n (%) female 49 90.7 male 5 9.3 age (years) mean (standard deviation) 48.1 (9.4) min 26.0 median 48.5 max 63.0 health insurance coverage type, n (%) preferred provider organization 41 75.9 health maintenance organization 8 14.8 worker’s compensation/motor vehicle/third-party liability 0 0.0 medicaid 2 3.7 medicare/medicare supplemental 0 0.0 indemnity 0 0.0 other 5 9.3 rosacea-relevant medical conditions, n (%) none 42 77.8 depression 5 9.3 migraine 5 9.3 conjunctivitis 4 7.4 blepharitis 1 1.9 corneal neovascularization/keratitis 0 0 patient attrition • study recruitment and patient attrition are summarized in figure 1. • 2,150 program-identified patients were invited to participate, 150 patients responded, and 54 met all eligibility criteria and were included in the study. results figure 1. study recruitment and patient attrition patients invited to participate in the study (n=2,150) eligible patients included in the study (n=54) patients responding to the invitation (n=150) ineligible not using azelaic acid foam as monotherapy (n=50, 36.0%) • incomplete survey (n=43, 28.7%)• no diagnosis of rosacea by a medical professional (n=2, 1.3%) • repeat survey responses (n=1, 0.7%) • figure 6. mean satmed-q scores 58.4 2.5 70.8 76.1 51.7 75.9 79.0 0 20 40 60 80 100 satmed-q score undesirable side effects treatment effectiveness convenience of use impact on daily activities medical care global satisfaction m e a n s co re satmed-q category key: satmed-q – satisfaction with medicines questionnaire. demographics • a total of 54 patients were included in the study. patient population characteristics and rosacea medical history are described in table 2. • participants were primarily female (90.7%), ranging in age from 26 to 63 years. • the majority of participants (77.8%) reported no rosacea-relevant medical conditions. • the most common subtypes reported by study participants were erythematotelangiectatic and papulopustular (74.1% each), with 59.3% of participants reporting “mild” rosacea symptoms (16.7% “absent”; 24.1% “moderate”) in the 4 weeks before enrollment. • only 13.0% of patients reported no previous rosacea treatment. figure 3. rosacea treatment concerns’ mean importance scores cost efficacy application dryness residue sun sensitivity itching scarring burning smell soreness stinging texture 9.3 10.0 9.0 8.0 6.3 10.0 8.0 8.0 3.0 0.0 0.0 0.0 0.0 0 2 4 6 8 10 m e a n i m p o rt a n ce s co re o f c o n ce rn concern figure 4. side effects with rosacea treatment none dryness stinging itching redness/worsening of rosacea burning residue left on face soreness uneven skin tone side effect 77.8% 13.0% 7.4% 5.6% 5.6% 3.7% 1.9% 0.0% 0.0% 0% 20% 40% 60% 80% 100% % o f r e sp o n d e n ts r e p o rt in g s id e e ff e ct figure 5. mean importance scores of rosacea treatment side effects 5.3 2.5 4.7 8.3 7.0 2.0 0.0 0.0 0 2 4 6 8 10 dryness stinging itching redness/worsening of rosacea burning residue left on face soreness uneven skin tone m e a n i m p o rt a n ce s co re o f s id e e ff e ct side effect treatment satisfaction and qol • the global satisfaction (satmed-q) mean score was 79.0 and treatment effectiveness mean score was 70.8 (figure 6). standardized scores for the satmed-q ranged from 0 to 100, with an overall score of 59.3 indicating feeling neutral and each additional 13.4-point increase indicating a clinically meaningful movement toward satisfaction. • the impact of rosacea on qol was “minimal” (mean dlqi score: 2.35). dlqi scores ranged from 0 to 30 (with 0–1 indicating rosacea has no effect on qol and 21–30 indicating rosacea has an extremely large effect on qol). exploratory analysis • in regression models used for the exploratory analysis, increasing dryness importance scores were significantly associated with worsening treatment satisfaction and qol in satmed-q and dlqi. • the most commonly reported topical agent for prior rosacea treatment was metronidazole gel (7.4%). patient concerns • the majority of patients reported no concerns (74.1%) with their treatment (figure 2). the biggest concern reported was cost (11.1% of patients), with a mean importance score (is) on a 10-point scale of 9.3 (figure 3). table 1. questionnaires included in the patient survey questionnaire details rosacea treatment preference questionnaire • 9-question survey composed of both aided and unaided questions. • assesses patient self-reported rosacea subtype and severity and evaluates drug characteristics that contribute to patient satisfaction/dissatisfaction and treatment decisions with rosacea topical treatments. • respondents list up to 5 concerns as well as up to 5 side effects with their current topical rosacea treatment experienced in the past 4 weeks and rate the importance of each reported concern or side effect. • respondents rank a list of pre-identified issues with topical rosacea treatment (eg, efficacy, cost, texture, dryness, etc) on a scale of importance from 0 to 10 (with 0 = not at all important; 10 = extremely important) in terms of how important the issue is when they consider using a new topical rosacea treatment. satmed-q • 17-question, validated, multidimensional, generic questionnaire designed for use in patients with any chronic disease treated with medicines measuring treatment satisfaction. • composed of 6 domains: − undesirable side effects (3 questions) − efficacy (3 questions) − convenience and ease of use (3 questions) − impact of medicine (3 questions) − medical follow-up/review (2 questions) − overall opinion (3 questions) dlqi • 10-question, widely used dermatology-related qol tool. • questions are general and cover symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment experience over the previous week. key: dlqi – dermatology life quality index; qol – quality of life; satmed-q – satisfaction with medicines questionnaire. statistical analysis • all study analyses conducted were exploratory and descriptive in nature. • the primary analysis population set included all patients who met the eligibility criteria and completed the survey. − baseline characteristics were calculated as mean values for continuous variables and percentages for categorical variables. − proportions of patients listing each concern or side effect related to azelaic acid foam in the rosacea treatment preference questionnaire were assessed. − all the importance or tolerability scores that patients assigned to each concern or side effect, the satisfaction score from the satisfaction with medicines questionnaire (satmed-q), and the qol score from the dermatology life quality index (dlqi) were computed and summarized using means standard deviations and medians as appropriate. • as an exploratory analysis to assess the association between concerns and side effects vs overall treatment satisfaction and overall qol, regression analyses were conducted. • a majority (77.8%) of patients reported no side effects (figure 4). dryness was the most commonly reported side effect (13.0%; is: 5.3). other side effects reported included stinging (7.4%, is: 2.5), itching (5.6%; is: 4.7), redness (5.6%; is: 8.3), and burning (3.7%; is: 7.0) (figure 5). patient concerns and treatment satisfaction in patients treated with azelaic acid foam for rosacea williamson t1; cameron j1; mcleod k2; turner b2; quillen a2; larose a1 bayer healthcare pharmaceuticals inc., whippany, nj, usa; 2xcenda, palm harbor, fl, usa continue >> patient concerns and treatment satisfaction in patients treated with azelaic acid foam for rosacea williamson t1; cameron j1; mcleod k2; turner b2; quillen a2; larose a1 bayer healthcare pharmaceuticals inc., whippany, nj, usa; 2xcenda, palm harbor, fl, usa sponsorship: this research was sponsored by bayer healthcare pharmaceuticals.presented at the 2018 winter clinical dermatology conference, january 12-17, 2018; lahaina, hawaii synopsis • rosacea is a common, chronic, inflammatory skin disorder affecting the convexities of the central face and can be categorized into 4 main subtypes: erythematotelangiectatic, papulopustular, phymatous, and ocular.1,2 • regardless of subtype, non-pharmacologic or behavioral interventions are useful for the management of skin flares; however, for patients with mild to moderate cases, especially of papulopustular rosacea, topical therapies are usually used as first-line therapy.1,3 • the use of topical medications, including metronidazole and azelaic acid gel, has shown efficacy in clinical trials vs placebo in reducing inflammatory lesion counts in patients with papulopustular rosacea; however, these treatments were associated with higher incidences of post-application skin discomfort, as patients reported burning, itching, and stinging sensations.1,2,4-6 • formulations like azelaic acid foam have the potential to offer improvements over the side effect profiles of these treatment options. objective • this study aimed to survey patients with rosacea about their concerns, treatment satisfaction, and quality of life (qol) associated with their azelaic acid foam treatment. methods study design • the study utilized a non-interventional, prospective, observational design and enrolled participants via email in collaboration with a patient support program, the rosacea concierge program. • a cross-sectional design was used to assess key patient concerns, treatment satisfaction, and qol related to azelaic acid foam for rosacea. sample selection • 2,150 patients from the united states (us) who were enrolled in the rosacea concierge program were invited to participate in the study. • all inclusion and exclusion criteria were patient reported. • inclusion criteria: − at least 18 years of age − diagnosis of rosacea by a medical professional − currently using azelaic acid foam as topical monotherapy for rosacea − willing and able to provide voluntary, informed consent to participate in the study • exclusion criteria: − use of any other topical treatment for rosacea at the time of enrollment study endpoints • eligible, consenting patients completed a 1-time survey assessing demographics, clinical characteristics (ie, rosacea-relevant comorbidities and complications), treatment history, and adverse events. • table 1 includes a brief overview of the 3 questionnaires included in the survey. figure 2. patient concerns with rosacea treatment 74.1% 11.1% 5.6% 5.6% 5.6% 5.6% 1.9% 2.0% 2.0% 2.0% 0.0% 0.0% 0.0% 0.0% 0% 20% 40% 60% 80% 100% none cost efficacy application dryness residue left on face sun sensitivity itching scarring burning smell soreness stinging texture % o f r e sp o n d e n ts r e p o rt in g c o n ce rn concern limitations • due to the limited respondent pool, further research is needed to confirm these results. − the international society of pharmacoeconomics and outcomes research (ispor) recommends that a minimum sample size of 200 patients is needed to obtain meaningful survey results in research on patient-reported outcomes. a total of 2,150 patients were invited to participate in this study, and 150 responded; however, only 54 met eligibility criteria and were enrolled in the study. conclusion • azelaic acid foam was well tolerated and efficacious, with less than 26% of participants reporting any concerns or side effects and 6% reporting a concern with treatment efficacy. • azelaic acid foam users reported favorable results in the domains of burning, itching, and stinging. • due to the limited respondent pool, further research is needed to confirm these results. references 1. webster gf. rosacea. med clin north am. 2009;93(6):1183-1194. 2. powell fc. clinical practice. rosacea. n engl j med. 352(8):793-803. 3. van zuuren ej, kramer s, carter b, graber ma, fedorowicz z. interventions for rosacea. cochrane database syst rev. 2011;(3):cd003262. 4. culp b, scheinfeld n. rosacea: a review. p&t. 2009;34(1):38-45. 5. berg m, liden s. an epidemiological study of rosacea. acta dermatol venereol. 1989;69:419-423. 6. wilkin j, dahl m, detmar m, et al. standard classification of rosacea: report of the national rosacea society expert committee on the classification and staging of rosacea. j am acad dermatol. 2002;(4):584-587. table 2. baseline characteristics and rosacea-relevant medical conditions total, n=54 gender, n (%) female 49 90.7 male 5 9.3 age (years) mean (standard deviation) 48.1 (9.4) min 26.0 median 48.5 max 63.0 health insurance coverage type, n (%) preferred provider organization 41 75.9 health maintenance organization 8 14.8 worker’s compensation/motor vehicle/third-party liability 0 0.0 medicaid 2 3.7 medicare/medicare supplemental 0 0.0 indemnity 0 0.0 other 5 9.3 rosacea-relevant medical conditions, n (%) none 42 77.8 depression 5 9.3 migraine 5 9.3 conjunctivitis 4 7.4 blepharitis 1 1.9 corneal neovascularization/keratitis 0 0 patient attrition • study recruitment and patient attrition are summarized in figure 1. • 2,150 program-identified patients were invited to participate, 150 patients responded, and 54 met all eligibility criteria and were included in the study. results figure 1. study recruitment and patient attrition patients invited to participate in the study (n=2,150) eligible patients included in the study (n=54) patients responding to the invitation (n=150) ineligible not using azelaic acid foam as monotherapy (n=50, 36.0%) • incomplete survey (n=43, 28.7%)• no diagnosis of rosacea by a medical professional (n=2, 1.3%) • repeat survey responses (n=1, 0.7%) • figure 6. mean satmed-q scores 58.4 2.5 70.8 76.1 51.7 75.9 79.0 0 20 40 60 80 100 satmed-q score undesirable side effects treatment effectiveness convenience of use impact on daily activities medical care global satisfaction m e a n s co re satmed-q category key: satmed-q – satisfaction with medicines questionnaire. demographics • a total of 54 patients were included in the study. patient population characteristics and rosacea medical history are described in table 2. • participants were primarily female (90.7%), ranging in age from 26 to 63 years. • the majority of participants (77.8%) reported no rosacea-relevant medical conditions. • the most common subtypes reported by study participants were erythematotelangiectatic and papulopustular (74.1% each), with 59.3% of participants reporting “mild” rosacea symptoms (16.7% “absent”; 24.1% “moderate”) in the 4 weeks before enrollment. • only 13.0% of patients reported no previous rosacea treatment. figure 3. rosacea treatment concerns’ mean importance scores cost efficacy application dryness residue sun sensitivity itching scarring burning smell soreness stinging texture 9.3 10.0 9.0 8.0 6.3 10.0 8.0 8.0 3.0 0.0 0.0 0.0 0.0 0 2 4 6 8 10 m e a n i m p o rt a n ce s co re o f c o n ce rn concern figure 4. side effects with rosacea treatment none dryness stinging itching redness/worsening of rosacea burning residue left on face soreness uneven skin tone side effect 77.8% 13.0% 7.4% 5.6% 5.6% 3.7% 1.9% 0.0% 0.0% 0% 20% 40% 60% 80% 100% % o f r e sp o n d e n ts r e p o rt in g s id e e ff e ct figure 5. mean importance scores of rosacea treatment side effects 5.3 2.5 4.7 8.3 7.0 2.0 0.0 0.0 0 2 4 6 8 10 dryness stinging itching redness/worsening of rosacea burning residue left on face soreness uneven skin tone m e a n i m p o rt a n ce s co re o f s id e e ff e ct side effect treatment satisfaction and qol • the global satisfaction (satmed-q) mean score was 79.0 and treatment effectiveness mean score was 70.8 (figure 6). standardized scores for the satmed-q ranged from 0 to 100, with an overall score of 59.3 indicating feeling neutral and each additional 13.4-point increase indicating a clinically meaningful movement toward satisfaction. • the impact of rosacea on qol was “minimal” (mean dlqi score: 2.35). dlqi scores ranged from 0 to 30 (with 0–1 indicating rosacea has no effect on qol and 21–30 indicating rosacea has an extremely large effect on qol). exploratory analysis • in regression models used for the exploratory analysis, increasing dryness importance scores were significantly associated with worsening treatment satisfaction and qol in satmed-q and dlqi. • the most commonly reported topical agent for prior rosacea treatment was metronidazole gel (7.4%). patient concerns • the majority of patients reported no concerns (74.1%) with their treatment (figure 2). the biggest concern reported was cost (11.1% of patients), with a mean importance score (is) on a 10-point scale of 9.3 (figure 3). table 1. questionnaires included in the patient survey questionnaire details rosacea treatment preference questionnaire • 9-question survey composed of both aided and unaided questions. • assesses patient self-reported rosacea subtype and severity and evaluates drug characteristics that contribute to patient satisfaction/dissatisfaction and treatment decisions with rosacea topical treatments. • respondents list up to 5 concerns as well as up to 5 side effects with their current topical rosacea treatment experienced in the past 4 weeks and rate the importance of each reported concern or side effect. • respondents rank a list of pre-identified issues with topical rosacea treatment (eg, efficacy, cost, texture, dryness, etc) on a scale of importance from 0 to 10 (with 0 = not at all important; 10 = extremely important) in terms of how important the issue is when they consider using a new topical rosacea treatment. satmed-q • 17-question, validated, multidimensional, generic questionnaire designed for use in patients with any chronic disease treated with medicines measuring treatment satisfaction. • composed of 6 domains: − undesirable side effects (3 questions) − efficacy (3 questions) − convenience and ease of use (3 questions) − impact of medicine (3 questions) − medical follow-up/review (2 questions) − overall opinion (3 questions) dlqi • 10-question, widely used dermatology-related qol tool. • questions are general and cover symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment experience over the previous week. key: dlqi – dermatology life quality index; qol – quality of life; satmed-q – satisfaction with medicines questionnaire. statistical analysis • all study analyses conducted were exploratory and descriptive in nature. • the primary analysis population set included all patients who met the eligibility criteria and completed the survey. − baseline characteristics were calculated as mean values for continuous variables and percentages for categorical variables. − proportions of patients listing each concern or side effect related to azelaic acid foam in the rosacea treatment preference questionnaire were assessed. − all the importance or tolerability scores that patients assigned to each concern or side effect, the satisfaction score from the satisfaction with medicines questionnaire (satmed-q), and the qol score from the dermatology life quality index (dlqi) were computed and summarized using means standard deviations and medians as appropriate. • as an exploratory analysis to assess the association between concerns and side effects vs overall treatment satisfaction and overall qol, regression analyses were conducted. • a majority (77.8%) of patients reported no side effects (figure 4). dryness was the most commonly reported side effect (13.0%; is: 5.3). other side effects reported included stinging (7.4%, is: 2.5), itching (5.6%; is: 4.7), redness (5.6%; is: 8.3), and burning (3.7%; is: 7.0) (figure 5). patient concerns and treatment satisfaction in patients treated with azelaic acid foam for rosacea williamson t1; cameron j1; mcleod k2; turner b2; quillen a2; larose a1 bayer healthcare pharmaceuticals inc., whippany, nj, usa; 2xcenda, palm harbor, fl, usa background • hyperhidrosis is defined as uncontrollable and excessive sweat production beyond what is necessary to maintain thermal regulation and affects an estimated 4.8% of the total u.s. population and approximately 2% of those under the age of 18; more recent data include findings from an online survey in the u.s. showing that roughly 17% of teens report experiencing excessive sweating, with nearly 75% of those characterizing it as leading to major or moderate daily impairment.1,2 • in general, there is a lack of awareness of hyperhidrosis as a bona fide medical condition and an underappreciation for the extent of burden caused by the disease.3-7 though primary focal hyperhidrosis typically has a childhood/adolescent onset, very few studies exist on the impact and burden of the disease in younger patients compared with adult patients. – survey results show that nearly half of all those affected report waiting 10 or more years before seeking medical help for their excessive sweating.8 – this delay in seeking help occurs despite the fact that those suffering with hyperhidrosis have a decreased quality of life, including social embarrassment and negative effects on emotional/mental health and limiting daily activities.1,8-11 • here, we report results of a qualitative research collaboration, utilizing interviews and focus groups in children, adolescents (and their caregivers) and young adults to characterize the quality of life impact in this understudied population. additional findings from this study provide insights on experiences and perceived gaps in available resources for hyperhidrosis support, diagnosis and common management strategies. methods study design and participants • figure 1 summarizes the study features, which included a deductive qualitative design supported by in-person interviews in children with excessive sweating and their caregivers (ages 6-13 years) as well as in-person focus groups (no more than 4 participants per group) with adolescents (ages 14-17 years) and young adults (ages 18-30 years). adult participants were asked to reflect on their experiences living with hyperhidrosis when they were younger. • participants were recruited by third-party patient recruiters and a main hyperhidrosis patient advocacy organization (the international hyperhidrosis society [ihhs; www.sweathelp.org]). • a clinical diagnosis of moderate-to-severe hyperhidrosis, self-identification of excessive sweating, or identification of likely primary hyperhidrosis via targeted screening questions was required.12,13 – screening questions were hierarchical (i.e., a minimum number of hyperhidrosis-indicating responses were required for more detailed questioning). – participants 17 years of age or less required caregiver consent. • participants underwent an initial, online pre-screening followed by a validation phase. – eligibility was validated via phone, during which a trained recruiter confirmed online responses for study inclusion criteria. – compensation was offered for time spent in interviews. data collection • data were collected during 90-minute in-depth interviews or small focus groups conducted in september 2019 in houston, texas and atlanta, georgia. • professional moderators using a structured interview guide led the discussion to understand the emotions, perceptions, and adjustments made with respect to living (or caring for someone) with hyperhidrosis as well as treatment experience and awareness of the disease. • all interviews and focus groups were recorded and transcribed for subsequent content, linguistic, and thematic analysis to identify and categorize topics, ideas and patterns of meaning that were repeated. • interviewers led an emoji exercise, where respondents could select a visual cue in the form of an emoji icon to best capture how hyperhidrosis makes them feel; participants also completed drawings. figure 1. study summary conducted in september 2019 • prompted discussion via structured interview guide • emoji exercise • drawings focus groups participants recruited from atlanta, ga and houston, tx screening third party recruiter children (6-13 y) and caregivers n=25 adolescents (14-17 y) n=7 young adults (18-30 y) n=8 in-person interviews international hyperhidrosis society results study participants • characteristics of the 40 participants are described in table 1. – participants reported a wide range in the age of onset. – most participants reported experiencing excessive sweating in multiple focal areas. – areas with excessive sweating were generally consistent with focal hyperhidrosis, including palmar (96%), axillary (86%), plantar (86%), craniofacial (61%), back (61%), and inguinal (18%) regions. table 1. participant characteristics n=40 children (6-13 y)a and caregivers n=25 adolescents (14-17 y) n=7 young adults (18-30 y) n=8 % male 6/13 (46%) 2/7 (29%) 4/8 (50%) mean age (years) 10 16 25 mean age of onset 7 11 16 areas of hh involvement, n (%) palmar 13 (100%) 6 (86%) 8 (100%) plantar 10 (77%) 6 (86%) 8 (100%) axillary 11 (85%) 5 (71%) 8 (100%) craniofacial 12 (92%) 4 (57%) 1 (13%) back 9 (69%) 4 (57%) 4 (50%) inguinal (groin) 2 (15%) 2 (29%) 1 (13%) aincludes 13 children, including one set of twins, and 12 caregivers quality of life impact (children, adolescents, caregivers, and young adults) • age-dependent trends emerged with respect to quality of life impact, concurrent with progression through different life phases (figure 2). – young children (1st – 3rd grade) primarily demonstrate physical and functional impairment related to daily activities. – among 4th to 8th graders, physical impact increases as sweating worsens and expands to additional regions, resulting in significant functional impairment in school (difficulty holding pencils, using technology that requires tactile imprint). • importantly, children in this age group have grown more conscious of social norms, leading to an increased social/emotional impact and reduced academic, extracurricular, and social activity participation. – in the high school age group, all quality of life domains are negatively impacted, though financial impact was not as notable. • this group was most likely to report teasing/bullying from their peers and report increases in anxiety. • social situations (dating, dances, extracurricular activities) increase anxiety, worry, embarrassment, anger, shame, and frustration and may lead to restrictive or isolating adaptive behaviors. figure 2. quality of life impact varies across age groups representative quotes in their own words grades 1-3 grades 4-5 grades 6-8 grades 9-12 post high schooldomain impacted physical functional social limited limited limited limited limited limited emotional financial “ my best friends, they crack a joke with me about it. they're like, you look gross', or whatever, 'she's sweaty!” “ …what's going to happen if i come over there and i shake their hand, or they're going to want to go in for a hug… if i'm thinking about it, like leading up to it, that's the worst.” “i change my clothes multiple times a day so i can control everything i do! last night and today i've worn three different shirts and three different pairs of underwear because i just want to make sure i'm okay, yes, it's a self-conscious thing.” “ i've got to have a desk job because i can't be sweating on people. that helps more, actually, because you don't have to interact with as many people.” “ there is a lot of sweat on my feet, my hands, my face and body.” “ i don’t like taking shoes off in front of a lot of people, it just wears me out, my feet are just gross.” “i check if anyone is around and hide it so that no one can see, make sure it’s not obvious that i am sweating.” “ when my feet are sweating and i don’t have socks on it is hard to walk around and it feels like i am walking on water.” “ when i try to answer something in class i have to find a different way of putting my hand up [to hide damp armpits] … it’s really awkward.” “ i don’t want to talk to my friends about it because i don’t think they would understand.” • the burden of hyperhidrosis does not appear to be diminished in adulthood. – adults report limiting situations that make them sweat more (e.g., meeting new people, outdoor concerts). – functional impacts evolve as they are confronted with professional interactions (shaking hands, wearing business attire, working in an office, interacting with new people), which in turn may have a negative financial impact as a result of adapting professional choices and behaviors in order to navigate the disease. • across all age groups, language and visual depictions of associations with sweating were negative and dramatically described (e.g., damp, embarrassing, gross, disgusting). – this negative association was visualized through an emoji exercise in which the most common emotions across all age groups are sadness, embarrassment and anger (figure 3a). – in addition, the negative association was candidly represented through drawing, even among the youngest patients (figure 3b). . figure 3. negative association of sweating among children angry (n=4)embarrassed (n=7)sad (n=7) a. emoji exercise b. drawings “i feel amazing…i will never sweat again and maybe nobody would notice and my mother will stop telling me i stink all the time and i won’t have to keep my fan on at night, that i won’t be told that i smell like dirty children, that i won’t be sticky all the time, that my shirt won’t stick to my back…that my feet won’t feel that they came out of a box of old water. the best thing would be that i would feel comfortable.” sufferer, female 4th-6th grade “my drawing is in green because green is gross. sweating is like when my brother backwashes.” sufferer, female 4th-6th grade “it shows me sweating and feeling unwell.” sufferer, female 6th-8th grade “it shows i feel embarrassed… it’s constantly happening, it’s wet down my back.” sufferer, female 6th-8th grade “a happy person, not sweating!” sufferer, female 6th-8th grade “happy, regular, not sweating.” sufferer, female 6th-8th grade a world without sweat how sweating feels disease awareness • hyperhidrosis disease awareness among these participants was minimal (figure 4). figure 4. lack of hyperhidrosis awareness lack of disease awareness • a minority of participants (n=6) were aware of the term “hyperhidrosis,” with a few participants providing vague mentions of “hyper-something” or “something-hidro” in their responses. limited hcp engagement • less than half of the sample had consulted a pediatrician (n=8 of 20 pediatric participants), and even fewer (n=3 of 28 participants with excessive sweating) reported having seen a dermatologist. • participants often discussed these symptoms with their healthcare providers as part of an annual exam or during a visit for another reason as opposed to one specifically related to excessive sweating. suboptimal treatment • among the 28 participants with excessive sweating (not caregivers), only one had received a prescription for hyperhidrosis treatment. • of note, caregiver feedback was not systematically collected; however, moderators did note a reluctance by some caregivers to ‘medicalize’ the condition. several caregivers in the study (n=6) also suffer from hyperhidrosis themselves and are more conscious of the impact. while some of these were very supportive and understanding, other caregivers tended to downplay the impact of excessive sweating to protect their child’s self-esteem. management strategies • the most common coping strategies described by participants in this study generally fell into one of three categories: adapting daily living behaviors, adding hygiene steps, or changing social interactions (figure 5). – respondents noted the need to plan ahead to account for a change of clothes and report making specific clothing choices (eg, loose-fitting, colors that won’t show sweat stains). – in addition, children note particular school behaviors that are adapted in order to minimize their worry (eg, avoiding raising their hand in class, bringing towels to absorb sweat, or minimizing activity in gym class). – though data were not systematically collected, gender-specific differences were most evident among adolescents with respect to physical activity, with female adolescents/older children more likely to comment on restricting their physical activity than male respondents. – in addition, adolescent female sufferers appeared more likely than male counterparts to experience a high emotional burden due to self-esteem issues (e.g., concerns about appearance, limitations in clothing choices) and were more likely to carry additional hygiene products with them. • figure 5. management strategies used across hyperhidrosis sufferers adapting daily living behavior clothing choices adding hygiene steps general hygiene keeping clothes clean changing social interactions isolating behaviors clothing choices highly impacted: • loose clothing; cotton or dry-fit fabrics; light or dark colors that don't show sweat/stains • absorbent socks; avoiding plastic sandals • washing shoes, inserts or frequent replacements • wearing layers even in hot weather to hide sweat • shower 1-3 times/day • frequent washing, showering, and wiping • increased use of antiperspirants and powders • ensure access to hygiene aids throughout day (spare antiperspirant / wipes / towels, and clothes) • shoe washing, buying inserts, replacing frequently • spare clothes kept in locker/ bag / car from older childhood onwards • order of extra school uniforms • high laundry burden from regular washing of multiple clothing changes each day • mentions of wearing maxipads / napkins under armpits to soak up sweat • older children (4th 5th and 6th 8th grade) and adolescents avoid putting up hand in class / raising arms in public; avoid joining in activities, avoid high fives or other hand contact. • older children / adolescents (esp. females) may avoid activity at recess / pe to avoid sweating (though others like physical activity as sweating is "permissible") conclusions • one of the main objectives of this study was to better understand the impact to individual quality of life domains in the youngest hyperhidrosis patients. to our knowledge, this study is the first to describe quality of life impact across age groups in a pediatric population who suffer with excessive sweating. • the interview and focus group data show that there is an evolution of quality of life impact, with a clear impact within the functional domain at even the earliest ages and increasing social/emotional burden developing over time. this phenomenon has not been documented previously in the literature. • disease awareness in this study was low, and participants had minimal experience with treatment beyond basic coping mechanisms, which underscores the need to raise awareness of this disease and of available treatment options, including among healthcare professionals, particularly given that effective treatment options are available and can improve symptoms and quality of life.14-16 • the value of the current study is that it represents a first step for subsequent systematic data collection in pediatric hyperhidrosis patients, data that are sorely needed to guide optimal management of these patients. the results of this research are currently being used to inform the development of a large, quantitative survey to further understand the awareness and impact of hyperhidrosis on a young person’s life. references 1. doolittle j, walker p, mills t, thurston j. hyperhidrosis: an update on prevalence and severity in the united states. arch dermatol res. 2016;308(10):743-749. 2. hebert a, glaser da, ballard a, pieretti l, trindade de almeida a, pariser d. prevalence of primary focal hyperhidrosis (pfhh) among teens 12-17 in us population. oral (latebreaker) presented at 75th annual meeting of the american academy of dermatology; 2017; orlando, fl. 3. augustin m, radtke ma, herberger k, kornek t, heigel h, schaefer i. prevalence and disease burden of hyperhidrosis in the adult population. dermatology. 2013;227(1):10-13. 4. ro km, cantor rm, lange kl, ahn ss. palmar hyperhidrosis: evidence of genetic transmission. journal of vascular surgery. 2002;35(2):382-386. 5. wadhawa s, agrawal s, chaudhary m, sharma s. hyperhidrosis prevalence: a disease underreported by patients and underdiagnosed by physicians. indian dermatol online j. 2019;10(6):676-681. 6. gelbard cm, epstein h, hebert a. primary pediatric hyperhidrosis: a review of current treatment options. pediatr dermatol. 2008;25(6):591-598. 7. shalaby m, abd el hay s. hyperhidrosis in children and review of its current 8. evidence-based management. ann pediatr surg 2015;11:169-172. 9. glaser da, hebert a, pieretti l, pariser d. understanding patient experience with hyperhidrosis: a national survey of 1,985 patients. j drugs dermatol. 2018;17(4):392-396. 10. cetindag ib, boley tm, webb kn, hazelrigg sr. long-term results and quality-of-life measures in the management of hyperhidrosis. thorac surg clin. 2008;18(2):217-222. 11. hamm h. impact of hyperhidrosis on quality of life and its assessment. dermatol clin. 2014;32(4):467-476. 12. kamudoni p, mueller b, halford j, schouveller a, stacey b, salek ms. the impact of hyperhidrosis on patients’ daily life and quality of life: a qualitative investigation. health qual life outcomes. 2017;15(1):121. 13. glaser da, hebert aa, pariser dm, solish n. primary focal hyperhidrosis: scope of the problem. cutis. 2007;79(5 suppl):5-17. 14. hornberger j, grimes k, naumann m, et al. recognition, diagnosis, and treatment of primary focal hyperhidrosis. j am acad dermatol. 2004;51(2):274-286. 15. bohaty br, hebert aa. special considerations for children with hyperhidrosis. dermatol clin. 2014;32(4):477-484. 16. ihhs. hyperhidrosistreatment algorithms https://www.sweathelp.org/treatments-hcp/clinical-guidelines/hyperhidrosis-treatment-algorithms.html. updated september 23 2018. accessed june 3, 2019. 17. ihhs. treatment overview https://www.sweathelp.org/treatments-hcp/treatment-overview.html. accessed june 3, 2019. quality of life impact and awareness of primary focal hyperhidrosis in children and adolescents z.p. rice,a l.j. pieretti,b a. wheeler,c j. payne,c k.k. gillard,d t. devlin,d and a.a. heberte adermatology associates of georgia, atlanta, ga; binternational hyperhidrosis society, center valley, pa; ccello health insight, new york, ny; ddermira, inc., a wholly-owned subsidiary of eli lilly and company, menlo park, ca; euthealth mcgovern medical school, houston, tx poster presented virtually at the fall clinical dermatology conference • october 29 november 1, 2020 skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 340 short communications serum sickness secondary to fluoxetine fatema s. esaa, baa; pooja r. shah, mdb; and lisa a. beck, mdb auniversity of rochester school of medicine and dentistry, rochester, new york bdepartment of dermatology, university of rochester medical center, rochester, new york a 15-year-old female with past medical history significant for generalized anxiety disorder, ptsd, and depression was admitted to the hospital for suicidal ideation. her psychiatric symptoms were not responsive to sertraline, prompting a crosstaper with fluoxetine 20mg. three days later, the patient developed an itchy cutaneous eruption associated with new-onset joint pain and swelling in her hands, wrists, and shoulders. skin examination was notable for blanchable, confluent, polycyclic, erythematous patches and plaques consistent with urticaria on the chest, abdomen, back (figure 1), upper extremities (figure 2), and thighs, although sparing face and neck. lymph node examination was normal. laboratory testing revealed a normal complete blood count (cbc), comprehensive metabolic panel (cmp), and erythrocyte sedimentation rate (esr), but an elevated c-reactive protein (crp) (45 mg/l), low-normal complement c3 (89 mg/dl), and low complement c4 (5 mg/dl). the cutaneous eruption and joint complaints resolved within a week after discontinuation of fluoxetine, and in response to treatment with topical triamcinolone 0.1% ointment. repeat laboratory testing within two weeks showed that c3 and c4 complement levels had returned to normal (128 and 31 mg/dl, respectively). given the temporal association with the administration of a new drug and the concurrence of dermatitis, arthralgias, and hypocomplementemia, this was most consistent with a case of serum sickness. figure 1. confluent, polycyclic, blanchable erythematous plaques over the back. case report skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 341 drug-related cutaneous eruptions are common, affecting approximately 2-3% of hospitalized patients, and varying in severity from benign to life-threatening.1 serum sickness is a rare, systemic, immunologic condition, often presenting with fever, rash, and joint pain. it is caused by the deposition of immune complexes in blood vessels and other tissues, resulting in complement activation and consumption and ensuing inflammation. a serum sickness-like reaction (sslr) presents very similarly and spontaneously resolves with withdrawal of the culprit drug. while the mechanism for sslrs is not well understood, it is thought to be distinct from a true serum sickness and typically does not present with hypocomplementemia, vasculitis, lymphadenopathy, or hepatic and renal dysfunction. a number of drug classes including antibiotics, beta-blockers, and antidepressants have been implicated in sslrs, with only 3 reported cases associated with fluoxetine.3-5 given the benign clinical course, absence of organ dysfunction, and onset of rash within few days of drug onset, our patient was initially diagnosed with a serum sickness-like reaction secondary to fluoxetine. however, the presence of hypocomplementemia in our patient is highly suggestive of a true serum sickness rather than sslr, as this is often the distinguishing factor between the two conditions. furthermore, the resolution of hypocomplementemia within weeks of discontinuation of the culprit drug (fluoxetine) supports immune complex deposition as the underlying etiology. providers should be aware that rarely serum sickness may occur with administration of figure 2. blanchable erythematous patches over the bilateral forearms and dorsal hands. non-biologic drugs as was the case with our patient. serum sickness with fluoxetine, although rare, has been reported.5,6 although our patient was young and relatively healthy, such a reaction has the potential for severe consequences especially in patients with immunosuppression, autoimmune disease, or other significant comorbidities. conflict of interest disclosures: none funding: none. discussion skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 342 corresponding author: pooja r. shah, md department of dermatology, university of rochester medical center 601 elmwood ave, po box 697 rochester, ny 14642 pooja_shah@urmc.rochester.edu references: 1. roujeau, jc, stern rs. severe adverse cutaneous reactions to drugs. n engl j med 1994; 331:1272-1285 2. schryver sd, netchiporouk e, benshoshan m. severe serum sicknesslike reaction: challenges in diagnosis and management. j clin exp dermatol res 6:279. 3. shapiro, le, knowles, sr, shear, nh. fluoxetine-induced serum sicknesslike reaction. annals of pharmacotherapy 1997; 31 (7-8) 4. warnock jk, morris dw. adverse cutaneous reactions to antidepressants. am j clin dermatol. 2002;3(5):329-39. 5. miller, l, bowman, r, mann, d, tripathy, a. a case of fluoxetineinduced serum sickness. am j psychiatry 1989; 146:1616–7 6. vincent, a, baruch, m. serum sickness induced by fluoxetine. the american journal of psychiatry 1991; 148 (11):1602-3. mailto:pooja_shah@urmc.rochester.edu skin january 2019 volume 3 issue 1 copyright 2018 the national society for cutaneous medicine 51 compelling comments dermoscopy: past and future andrew m armenta, bs1, alex steele, bs2, paul r massey, md3 1university of texas medical branch, school of medicine, galveston, texas 2university of texas health and science center at san antonio, school of medicine, san antonio, texas 3division of dermatology, dell medical school, university of texas at austin, austin, tx in vivo cutaneous microscopy was born in the mid-17th century when nascent microscopes were employed to examine nailbed vessels [1]. in 1878, german physicist ernst abbe discovered that oil applied to the epidermis rendered it translucent [1]. dermoscopy was first applied in the united states by dermatologist jeffrey michael of houston, texas in 1922.1 american surgeon leon goldman described dermoscopy’s effectiveness in pigmented skin lesions1 and in 1971, scottish dermatologist rona mackie argued that dermoscopy could be used to distinguish benign and malignant lesions. 1 despite these advances, widespread use of dermoscopy was still limited by impracticality (figure 1). 1 initially, the size of microscopes a limiting factor and the first portable dermatoscopes emitted light weakly. in 2001, a stronger, polarized light with a crosspolarization filter was added to the handheld dermatoscope1, allowing the viewer to examine deeper structures in the skin by eliminating reflected light from the highly refractive stratum corneum. this advance also provided the flexibility to use the dermatoscope without contact fluid. 1 eighty one percent of dermatologists report using dermoscopy regularly, including 98% of dermatologists recently graduated from training2, and the study of dermoscopy has evolved to become a field unto itself. the first consensus conference on dermoscopy was held in 1989. today the international dermoscopy society boasts over 13,000 members from 168 countries, holds annual meetings and publishes a journal dedicated to dermoscopy. figure 1: the zeiss operation microscope utilized by dr. rona mackie in a 1971 study on cutaneous microscopy. reproduced with permission from british journal of dermatology. skin january 2019 volume 3 issue 1 copyright 2018 the national society for cutaneous medicine 52 dermoscopy may prove an essential part of a virtual evaluation as the practice of teledermatology widens. arzberger et al. reported excellent correlation in the management decisions of pigmented lesions (e.g. self-monitoring, short term follow up, excision) between in-person and teledermoscopic evaluation in a high-risk melanoma cohort, a finding which has been replicated in other studies.3 these data speak to the potential benefit of teledermoscopy for providers and patients who may not have in-person access to a dermatologist and reflect the bright future of dermoscopy in the house of dermatology. conflict of interest disclosures: none. funding: none. corresponding author: paul r. massey, md division of dermatology, dell medical school austin, texas prmassey@ascension.org references: 1. stolz w, braun-falco o, semmelmayer u, kopf a. the encyclopedia of visual medicine series: atlas of dermoscopy. abingdon, uk: taylor &francis; 2004. 2. murzaku, e.c., s. hayan, and b.k. rao, methods and rates of dermoscopy usage: a cross-sectional survey of us dermatologists stratified by years in practice. j am acad dermatol, 2014. 71(2): p. 393-5. 3. arzberger e., curiel-lewandrowski c., blum a, chubisov d., oakley a., rademaker m., soyer h., hofmannwellenhof r. teledermoscopy in highrisk melanoma patients: a comparative study of face-to-face and teledermatology visits. acta derm venereol. 2016 aug 23;96(6):779-83. mailto:prmassey@ascension.org results: rapid and effective in conclusion, bpx-01 2% minocycline topical gel resulted in rapid improvement and better outcomes than vehicle control in the treatment of moderateto-severe non-nodular inflammatory acne vulgaris. this treatment may provide an effective new option with a favorable safety profile and potential for high patient compliance. this work was sponsored by biopharmx; all investigators were active participants in the trial. bpx-01 is limited by federal or us law to investigational use only. introduction a reduction of 25% in the number of inflammatory lesions is considered clinically important and is recognized by patients as an indicator of an effective treatment. because this milestone was reached within two weeks of treatment with bpx -01, it has the potential to result in optimal treatment compliance and improved patient satisfaction. the rapid rate of improvement (43% after four weeks) outpaced that observed in a separate clinical trial with oral minocycline for acne in which improvement exceeding 40% required 12 weeks of treatment,4 with much lower systemic exposure. additionally, bpx-01 2% resulted in 58.5% reduction in lesions with consistent trends toward improvement in iga, pgi, and satisfaction scores. the medication was well tolerated with good safety profile and was largely undetectable in blood plasma, hence no systemic side effects are anticipated. 1mount sinai st luke’s, new york ny; 2del rosso dermatology research center, las vegas nv; 3acrc trials/innovative dermatology, plano, tx; 4image dermatology, montclair, nj; 5dermatology consulting services, high point, nc; 6international clinical research-tennessee, murfreesboro, tn; 7international clinical research, sanford, fl; 8ds research, louisville, ky; 9tennessee clinical research center, nashville, tn; 10skin research institute, coral gables, fl; 11austin institute for clinical research, heatherwilde, tx; 12progressive clinical research, san antonio, tx; 13medaphase, newnan, ga; 14medical & cosmetic dermatology, santa monica, ca; 15premier clinical research, spokane, wa; 16biopharmx, menlo park, ca methods this phase 2b study was intended to describe the safety and efficacy of topical minocycline in the treatment of inflammatory acne vulgaris. acne affects up to 50 million americans annually.1 it can be caused by sebaceous gland hyperactivity, abnormal keratinocyte desquamation, and bacteria-related local inflammatory changes.2,3 comedones and inflammatory papules, pustules and nodules are sites of proliferation for propionibacterium acnes bacteria. bpx-01 topical minocycline gel the study medication: bpx-01 is the first completely solubilized minocycline gel for topical use. it is intended for the treatment of non-nodular, moderate-to-severe inflammatory acne vulgaris in patients nine years of age and older. its preliminary safety and efficacy profile have been demonstrated in extensive preclinical testing and a phase 2a study: strong efficacy » stabilizes & solubilizes minocycline » delivered directly to pilosebaceous unit » targeted penetration strong safety profile » low dose: 1% and 2% minocycline » minimizes side effects » low systemic exposure » rapidly absorbing » non-staining » non-oily » non-fluorescing » very high patient satisfaction in clinical trials positive patient experience primary endpoint achieved: reduction in p. acnes colonies change from baseline at 4 weeks mean (log10) percentage bpx-01 minocycline (n=17) -1.04 -90.9% vehicle (n=7) -0.46 -65.3% » no drug-related adverse events » no detectable plasma minocycline » no cutaneous toxicity » 100% patient satisfaction r e s u lt s favorable secondary and safety endpoints » randomized, double-blind, vehicle-controlled, dose-ranging study in 226 patients with moderate-to-severe acne » 12-week study evaluating 3 arms: bpx-01 1% , bpx-01 2%, vehicle » conducted at 15 u.s. sites » patients ages 9 to 40, iga* of 3 or 4, 20-60 non-nodular inflammatory lesions 1. bickers dr, lim hw, margolis d, weinstock ma, goodman c, faulkner e, et al. the burden of skin diseases: 2004 a joint project of the american academy of dermatology association and the society for investigative dermatology. j am acad dermatol. 2006;55:490-500. 2. gollnick h, cunliffe w, berson d, dreno b, finlay a, leyden jj, et al. management of acne: a report from a global alliance to improve outcomes in acne. j am acad dermatol. 2003;49(1 suppl):s1-37. 3. weiss js. acne: evolving concepts of pathogenesis need to guide therapeutic developments. j drugs dermatol. 2013; 12: s66. 4. torok hm. extended-release formulation of minocycline in the treatment of moderate-tosevere acne vulgaris in patients over the age of 12 years. j clin aesthet dermatol. 2013;6[7]:19–22. poster presented at the 2017 fall clinical dermatology conference®; las vegas, nv; october 12-15, 2017. primary endpoint: absolute mean change in number of inflammatory lesions from baseline at week 12en d p o in t s secondary endpoint: proportion of subjects with at least a two-grade reduction in iga* to clear or almost clear (0 or 1) at week 12 s t u d y d e s ig n » minocycline plasma concentrations » safety – adverse events » cutaneous tolerance » patient satisfaction » non-inflammatory lesion reduction * investigator global assessment; based on scale of 0 (clear) to 4 (severe) e x p l o r a t o r y / s a f e t y bpx-01 1% bpx-01 2% vehicle subjects per arm 73 72 74 absolute mean change in inflammatory lesions at week 12 15.5 15.4 11.2 p-value 0.0543 0.0352 percent reduction in inflammatory lesions 54.4% 58.5% 43.8% p-value 0.0765 0.0256 15% » primary endpoint: absolute mean change in number of inflammatory lesions from baseline at week 12 » the above analysis reflects the intent to treat (itt) population of 219 rapid rate of improvement in bpx-01 2% arm: key takeaways » > 25% reduction in lesions at week 2 with both doses » a 25% improvement is considered meaningful to patients » reaching a 25% improvement within 2 weeks may lead to patient compliance and satisfaction with treatment » 43.3% reduction in lesions at week 4 with 2% dose » 58.5% reduction in lesions at week 12 with 2% dose week 12 59% clear trend in iga reduction for 2% treatment arm bpx-01 1% bpx-01 2% vehicle subjects per arm 73 72 74 proportion with ≥ twograde reduction and clear or almost clear 20.5% 25.0% 17.6% p-value (vs vehicle) >0.9999 0.5445 » secondary endpoint*: 25% of subjects in the 2% arm demonstrated at least a twograde reduction in iga to clear or almost clear (0 or 1) » 7.4% separation between 2% dose and vehicle informs sample size for confirmatory phase 3 trials 7.4% demonstrated rapid lesion reduction reduction in inflammatory lesions safety endpoint: systemic exposure » treatment-related adverse events occurred in 0.4% of subjects » generally safe and well tolerated in this study » no serious treatment-related adverse events » no photosensitivity or postinflammation hyperpigmentation was reported » no staining and/or skin discoloration was reported would you consider using again? yes / no 86% of subjects would use bpx-01 2% again bpx-01 1% bpx-01 2% vehicle baseline bloq bloq bloq week 4 bloq bloq bloq week 12 bloq bloq* bloq *one subject measured 42 ng/ml at 12 weeks; no aes bloq=below limit of quantification (10 ng/ml) » minocycline was undetectable in the plasma of 99.5% of subjects. » further support for no anticipated systemic side effects » highly sensitive assay with lloq for minocycline of 10 ng/ml in plasma yes nopositive patient experience: bpx-01 2% shows potential for high patient compliance p e rc e n ta g e r e d u ct io n v s. b a se li n e * study was not powered for this endpoint week 2 >25% week 4 43% onset of benefit: bpx-01 vs. oral minocycline er 0.0% -43.3% -49.5% -58.5% -70% -60% -50% -40% -30% -20% -10% 0% baseline week 4 week 8 week 12 bpx-01 2% 0.0% -31.6% -39.9% -44.5% -70% -60% -50% -40% -30% -20% -10% 0% baseline week 4 week 8 week 12 oral minocycline er *see reference #4 below. the results of two phase 3 studies were combined for comparison. p e rc e n ta g e l e si o n r e d u ct io n vs . b a se li n e » not conducted as a head-to-head trial. while recognizing that these trial data cannot be directly compared, bpx-01 may demonstrate a more rapid rate of improvement when compared to clinical data available for oral er minocycline.* » bpx-01 may demonstrate a greater percentage of reduction in inflammatory lesions at all time points. 79% 1 2 3 4 5 (most favorable) ease of use and application scale of 1-5 79% of subjects thought bpx-01 2% was easy to use and apply andrew alexis,1 james del rosso,2 seemal r. desai,3 jeanine downie,4 zoe diana draelos,5 christina feser,6 rion forconi,7 joseph fowler,8 michael gold,9 joely kaufman-janette,10 edward lain,11 mark lee,12 mark ling,13 ava shamban,14 william werschler,15 annamarie daniels16 rapid improvement with bpx-01 minocycline topical gel in the treatment of moderate-to-severe inflammatory acne vulgaris: a randomized, double-blind, vehicle-controlled study -70% -60% -50% -40% -30% -20% -10% 0% baseline week 4 week 8 week 12 bpx-01 1% bpx-01 2% vehicle baseline 0.0% 0.0% 0.0% week 2 -32.8% -27.6% -25.7% week 4 -39.7% -43.3% -25.3% week 8 -50.5% -49.5% -38.7% week 12 -54.4% -58.5% -43.8% adverse events baseline week 2 week 4 week 8 week 12 25% reduction fc17posterbiopharmxrapidimprovementalexis.pdf introduction � a foam formulation of fixed combination calcipotriol 50 µg/g (cal) and betamethasone 0.5 mg/g (as dipropionate; bd) has been developed as a treatment option for patients with psoriasis1 � the phase iii pso-fast (cal/bd foam in psoriasis vulgaris, a four-week, vehicle-controlled, efficacy and safety trial) study demonstrated that cal/bd foam provides significantly greater efficacy than vehicle in patients with psoriasis2 � itch is a common and distressing aspect of psoriasis that negatively impacts on a patient’s quality of life, causing discomfort, potentially aggravating the lesion, and often leading to sleep loss3,4 � in this sub-analysis of the pso-fast study we assessed changes in itch during treatment with cal/bd foam, in patients who had clinically relevant itch at baseline (defined as visual analogue scale [vas] score of >30)5 methods study design and patients � pso-fast was a phase iii, multicentre, double-blind, randomized study conducted at 27 sites in the united states (nct01866163)2 � patients were randomized (3:1) to cal/bd foam or foam vehicle once daily for up to 4 weeks � patient eligibility: aged ≥18 years; at least mild psoriasis, according to the physician’s global assessment of disease severity; modified psoriasis area and severity index (mpasi) score of ≥2; and, 2–30% body surface area (bsa; trunk and/or limbs) affected by psoriasis itch assessment � itch was evaluated based on a vas (range 0–100 mm, where 0 is no itch and 100 mm is the worst itch imaginable) � patients assessed maximal itch intensity over the 24-hour period prior to days 3 and 5, and at weeks 1, 2, and 4 using a subject diary statistical analysis � patients included in this sub-analysis were those with a baseline itch vas score >30, ie, of clinical relevance5 � change in vas scores from baseline for cal/bd and vehicle foam treatment groups were compared using analysis of variance (anova), adjusting for baseline score and pooled centres � the proportion of patients achieving a 70% reduction in itch were compared between treatment groups using the mantel-haenszel method, adjusting for pooled centres results patients � in total, 323 patients were randomized to cal/bd foam, and 103 to vehicle – of these, 225/323 (70%) patients in the cal/bd foam treatment group, and 75/103 (73%) patients in the vehicle group had a baseline itch vas score of >30 � among patients with baseline itch vas score of >30, mean (±sd) baseline score was 66.1 ± 19.9 in the cal/bd foam group and 69.9 ± 18.1 in the vehicle group � treatment groups were generally well balanced in terms of demographic and baseline factors, although the gender balance was different between cal/bd foam and vehicle (table 1) assessment of itch � patients receiving cal/bd foam reported significant and rapid reduction in itch relief compared with patients receiving vehicle – itch relief was observed by day 3 and continued to improve during the 4-week study (figure 1; table 2) � significant treatment differences were noted at the first assessment on day 3 (p=0.019) and were maintained at all subsequent time points throughout treatment (figure 1; table 2) � at week 4, 84.7% of patients using cal/bd foam achieved a 70% reduction in their itch (figure 2) – this was statistically significantly greater than vehicle (39.7%; or 7.6; 95% ci 4.2, 14.0; p<0.001) treatment with fixed combination calcipotriol 50 µg/g and betamethasone dipropionate 0.5 mg/g foam provides rapid and significant itch relief in patients with psoriasis linda stein gold,1 paul yamauchi,2 david pariser,3 zhenyi xu,4 marie louise østerdal,4 jerry bagel5 1henry ford health system, detroit, mi, usa; 2division of dermatology, david geffen school of medicine at ucla, los angeles, ca, usa; 3department of dermatology, eastern virginia medical school and virginia clinical research, inc., norfolk, va, usa; 4leo pharma a/s, ballerup, denmark; 5psoriasis treatment center of central new jersey, east windsor, nj, usa p1933 poster presented at the 26th eadv congress, geneva, switzerland, 13–17 september 2017 acknowledgements � this study was sponsored by leo pharma. medical writing support was provided by andrew jones, phd, from mudskipper business limited, funded by leo pharma references 1. paul c et al. expert opin pharmacother 2017;18:115–21 2. leonardi c et al. j drugs dermatol 2015;14:1468–77 3. korman nj et al. dermatol online j 2015;21 4. szepietowski jc & reich a. curr probl dermatol 2016;50:102–10 5. stander s et al. acta derm venereol 2013;93:509–14 6. koo j et al. j dermatolog treat 2016;27:120–7 7. paul c et al. j eur acad dermatol venereol 2017;31:119–26 8. queille-roussel c et al. clin drug investig 2015;35:239–45 9. stein gl et al. j drugs dermatol 2016;15:951–7 table 1. baseline demographic and clinical characteristics of patients with baseline itch score >30 cal/bd foam (n=225) vehicle (n=75) age, years 50.6 (14.0) 45.6 (12.9) male:female, n (%) 132:93 (59:41) 28:47 (37:63) race, n (%) white 194 (86.2) 65 (86.7) duration of psoriasis, years 15.1 (13.5) 15.0 (11.1) bsa affected, % 8.1 (7.0) 8.3 (6.8) pga, n (%) mild 29 (12.9) 11 (14.7) moderate 174 (77.3) 53 (70.7) severe 22 (9.8) 11 (14.7) mpasi score 7.8 (5.0) 8.4 (7.3) data are shown as mean (standard deviation [sd]), unless otherwise stated table 2. adjusted mean itch vas scores during treatment in patients with baseline itch score >30 cal/bd foam, mean change vehicle, mean change mean difference (95% ci) p value day 3 –31.4 –23.5 –7.86 (–14.41, –1.30) 0.019 day 5 –41.4 –29.1 –12.25 (–18.65, –5.85) <0.001 week 1 –46.2 –30.8 –15.42 (–21.82, –9.01) <0.001 week 2 –51.7 –31.9 –19.82 (–26.16, –13.47) <0.001 week 4 –56.7 –31.1 –25.60 (–31.96, –19.25) <0.001 ci, confidence interval figure 1. adjusted mean change in itch vas scores over 4 weeks in patients with baseline itch score >30 (observed cases) bars represent 95% confidence intervals (ci); *p=0.019; **p<0.001 cal/bd foam vs vehicle ad ju st ed m ea n ch an ge fr om ba se lin e in it ch v as sc or e cal/bd foam vehicle n=225 215 213 216 217 216 n=75 72 72 75 74 73 0 -10 -20 -30 -40 -50 -60 -70 0 day 3 * ** ** ** ** day 5 week 2 week 4week 1 figure 2. proportion of patients with baseline itch score >30 achieving a 70% reduction in itch by visit (observed cases) day pa tie nt s ( % ) cal/bd foam vehicle 90 80 70 60 50 40 20 0 42153 10 week 30 34.0 (n=215) 22.2 (n=72) 50.2 (n=213) 29.2 (n=72) 60.6 (n=216) 32.0 (n=75) 72.4 (n=217) 45.0 (n=74) 39.7 (n=73) 84.7 (n=216) p=0.002 p<0.001 p<0.001 p<0.001 � itch is considered one of the most distressing symptoms of psoriasis, but current treatment options are limited4 � this analysis of patients with psoriasis who had clinically relevant itch at baseline demonstrates that cal/bd foam leads to rapid and significant relief of itch, which continues to improve throughout treatment � these findings expand on the primary efficacy results of the pso-fast study, showing that cal/bd foam is highly efficacious and well tolerated in patients with psoriasis2,6-9 conclusions pcg-workstation-2 sticky note marked set by pcg-workstation-2 pcg-workstation-2 sticky note marked set by pcg-workstation-2 pcg-workstation-2 sticky note marked set by pcg-workstation-2 pcg-workstation-2 sticky note marked set by pcg-workstation-2 pcg-workstation-2 sticky note marked set by pcg-workstation-2 pcg-workstation-2 sticky note marked set by pcg-workstation-2 pcg-workstation-2 sticky note marked set by pcg-workstation-2 pcg-workstation-2 sticky note marked set by pcg-workstation-2 pcg-workstation-2 sticky note marked set by pcg-workstation-2 pcg-workstation-2 sticky note marked set by pcg-workstation-2 pcg-workstation-2 sticky note marked set by pcg-workstation-2 pcg-workstation-2 sticky note marked set by pcg-workstation-2 pcg-workstation-2 sticky note marked set by pcg-workstation-2 pcg-workstation-2 sticky note marked set by pcg-workstation-2 pcg-workstation-2 sticky note marked set by pcg-workstation-2 pcg-workstation-2 sticky note marked set by pcg-workstation-2 pcg-workstation-2 sticky note marked set by pcg-workstation-2 pcg-workstation-2 sticky note marked set by pcg-workstation-2 pcg-workstation-2 sticky note marked set by pcg-workstation-2 pcg-workstation-2 sticky note marked set by pcg-workstation-2 powerpoint-præsentation © mc2 therapeutics  1 phase 3 trial demonstrates superior patient treatment convenience of mc2-01 calcipotriene plus betamethasone dipropionate cream compared to current topical suspension adults mild to moderate psoriasis r mc2-01 cream (n=343) mc2-01 cream vehicle (n=115) cal/bdp topical suspension (n=338) 2 week followup introduction: pad™ technology has for the first time enabled formulation of mc2-01 cream is a first aqueous topical treatment of psoriasis containing the active ingredients calcipotriene and betamethasone dipropionate (0.005% / 0.064% w/w, cal/bdp). mc2-01 cream is based on pad™ technology and designed for high penetration of the actives combined with excellent cosmetic elegance. patient convenience data from a phase 3 trial is presented comparing mc2-01 cream to cal/bdp topical suspension (“cal/bdp ts”) in adults with mild to moderate psoriasis. methods: the phase 3, randomized, multicenter, investigator-blind, parallel-group trial evaluated the efficacy, safety and convenience of mc2-01 cream compared to mc2-01 vehicle and the cal/bdp ts (sourced as taclonex® topical suspension) in adult patients with psoriasis vulgaris on the body. the trial enrolled 796 patients at 55 clinical sites across the united states: mc2-01 cream (n=343), cal/bdp ts (n=338), mc2-01 vehicle (n=115). patients applied trial medication once daily for eight weeks. the primary objective was to demonstrate non-inferiority of mc201 cream to cal/bdp ts on pga treatment success at week 8. a novel patient treatment convenience scale (ptcs), currently being validated, was administered at week 1, week 4 and week 8 to evaluate patient acceptance of the topical formulations (fig. 5). the ptcs accumulates scores of five simple questions rated on an 10-point numeric rating scale with a high score indicating high convenience. an extra question evaluated overall satisfaction of the medical treatment. superiority of ptcs at week 8 comparing mc2-01 cream to cal/bdp ts was evaluated as a secondary endpoint. morten præstegaard1, birgitte vestbjerg1, johan selmer1, tove holm-larsen2 1mc2 therapeutics, hørsholm, denmark; 2pharma evidence, farum, denmark how easy was the treatment to apply to the skin? very difficult very easy 1 2 3 4 5 6 7 8 9 10 how greasy was the treatment when applying it to the skin? very greasy not greasy 1 2 3 4 5 6 7 8 9 10 how moisturized did your skin feel after applying the treatment? not moisturized very moisturized 1 2 3 4 5 6 7 8 9 10 how greasy did your skin feel after applying the treatment? very greasy not greasy 1 2 3 4 5 6 7 8 9 10 how much did treating your skin disrupt your daily routine? very disturbing not disturbing 1 2 3 4 5 6 7 8 9 10 overall, how satisfied were you with the medical treatment? not satisfied very satisfied 1 2 3 4 5 6 7 8 9 10 0 2 4 6 8 10 0 2 4 6 8 p tc s q ue st io n 2 weeks 0 2 4 6 8 10 0 2 4 6 8 p tc s q ue st io n 3 weeks 0 2 4 6 8 10 0 2 4 6 8 p tc s q ue st io n 4 weeks 0 2 4 6 8 10 0 2 4 6 8 p tc s q ue st io n 5 weeks 0 2 4 6 8 10 0 2 4 6 8 p tc s q ue st io n e weeks fig.3: primary efficacy variable: % pga treatment success 0 10 20 30 40 50 0 2 4 6 8 % p g a t re at m en t su cc es s weeks **** **** **** **** p < 0.0001 (mc2-01 cream vs. cal/bdp ts) mc2-01 cream cal/bdp ts mc2-01 vehicle 0 2 4 6 8 10 0 2 4 6 8 p tc s q ue st io n 1 weeks 1 2 3 4 5 e 1) how easy was the treatment to apply to the skin? 2) how greasy was the treatment when applying it to the skin? 4) how greasy did your skin feel after applying the treatment? 3) how moisturized did your skin feel after applying the treatment? 5) how much did treating your skin disrupt your daily routine? e) overall, how satisfied were you with the medical treatment? further evaluation of mc2-01 cream treatment convenience at week 1 (39.7 vs. 36.9, p<0.0001) and week 4 (40.2 vs. 37.1, p<0.0001) confirmed superiority compared to cal/bdp ts throughout treatment. analysis of single questions clarified that the highest preference for mc201 cream versus cal/bdp ts arose in questions “how greasy was the treatment when applying it to the skin” and “how greasy did your skin feel after applying the treatment”, showing that lower greasiness is a key differentiating feature of mc2-01 cream compared to the topical suspension (fig. 6). the extra question evaluating overall satisfaction with treatment followed the trend of other efficacy variables in the trial. the safety profile of mc2-01 cream was similar to that known for cal/bdp products. fig.4: secondary pro variable: patient treatment convenience 0 10 20 30 40 50 0 2 4 6 8 p at ie nt t re at m en t c on ve ni en ce e weeks **** ******** efficacy results: the phase 3 trial met its primary objective of treatment success, and data further showed superiority of mc2-01 cream versus cal/bdp ts at week 8 (mc2-01 cream 40.1% vs. cal/bdp ts 24.0%, p<0.0001) (fig. 3). the secondary endpoint assessing patient treatment convenience (ptcs) at week 8 demonstrated superiority of mc2-01 cream compared to cal/bdp ts (41.5 vs. 37.5, p<0.0001) (fig. 4). figure 2: phase 3 trial design betamethasone diproponate (bdp) requires ph>8 for stability vitamin d analogue requires ph 4-6 for stability potent corticosteroid calcipotriene (cal)  dual additive efficacy of cal and bdp  improved safety profile compared to the individual actives alone ‒ bdp counteracts potential skin irritation of cal ‒ cal mitigates potential skin atrophogenic effect of bdp  pad™ technology uniquely enables a stable combination of cal and bdp in an elegant and fast absorbing aqueous cream figure 1: rationale for mc2-01 cream figure 5: patient treatment convenience scale (ptcs) conclusions the phase 3 trial showed that mc2-01 cream has an improved overall efficacy compared to the current cal/bdp ts. superior patient convenience of mc2-01 cream enabled by the pad™ technology, including its lower greasiness, may increase treatment compliance among psoriasis patients, and positively impact real-life treatment outcomes even further. figure 6: ptcs individual questions mc2-01 cream cal/bdp ts mc2-01 vehicle mc2-01 cream cal/bdp ts mc2-01 vehicle mc2-01 cream cal/bdp ts mc2-01 vehicle mc2-01 cream cal/bdp ts mc2-01 vehicle mc2-01 cream cal/bdp ts mc2-01 vehicle mc2-01 cream cal/bdp ts mc2-01 vehicle mc2-01 cream cal/bdp ts mc2-01 vehicle slide number 1 effect of combination therapy on visible/non-visible symptoms, and disease burden associated with severe rosacea: results from a post-hoc analysis of a randomized controlled trial james del rosso, do1, mark jackson, md2, sandra johnson, md3, alison harvey, phd, ms4, rajeev chavda, md5 1jdr dermatology research/thomas dermatology, las vegas, nv; 2university of louisville, louisville, ky; 3johnson dermatology clinic, fort smith, ar; 4galderma laboratories, fort worth, tx; 5galderma s.a., tour-de-peilz, switzerland synopsis • rosacea affects over 16 million people in the us with symptoms in central areas of the face, causing flushing, stinging/burning, chronic erythema, and inflammatory lesions, with major negative impact on quality of life.1-3 • the disease is chronic and inflammatory in nature and burden typically extends beyond visible symptoms with impact on emotional, social, and psychological aspects of life.4 • in a global survey (n=710) evaluating impact of symptoms associated with disease burden in rosacea, non-visible symptoms such as itching, burning/pain, and swelling were significantly associated with high disease burden.4 • combination therapy with multiple mechanisms of actions are often used to manage symptoms associated with rosacea. however, limited numbers of controlled studies have evaluated impact of combination therapy vs monotherapy on reducing the signs and symptoms associated with rosacea.5 • ivermectin and doxycycline are two well-established molecules with proven efficacy and safety, targeting different and complementary pathological features of severe rosacea.5 conclusions combined ivm and dmr improved both visible (eg, inflammatory lesions, erythema, flushing) and non-visible symptoms (eg, stinging/burning) of rosacea. correlations between symptom reduction and dlqi suggest improvements in different aspects of quality of life. results from this phase 4 study and this post-hoc analysis emphasize the importance of targeting both the visible and nonvisible signs and symptoms in patients with severe rosacea with combination therapy to create best outcomes. acknowledgements this research was sponsored by galderma laboratories, fort worth, tx; medical writing support was provided by medicalwriters.com, new york, usa. references 1. steinhoff m, schmelz m, schauber j. facial erythema of rosacea aetiology, different pathophysiologies and treatment options. acta derm venereol. 2016;96(5):579–586. 2. schaller m, almeida lmc, bewley a, et al. recommendations for rosacea diagnosis, classification and management: update from the global rosacea consensus (rosco) 2019 panel. br j dermatol. august 2019. [epub ahead of print] 3. national rosacea society website. https://www.rosacea.org/rosacea-review/2010/winter/rosacea-now-estimated-to-affect-at-least-16-million-americans. accessed november 21, 2019. 4. tan j, steinhoff m, bewley a, gieler u, rives v. characterizing high-burden rosacea subjects: a multivariate risk factor analysis from a global survey. j dermatolog treat. june 2019. [epub ahead of print] 5. schaller m, kemeny l, havlickova b, et al. a randomized phase 3b/4 study to evaluate concomitant use of topical ivermectin 1% cream and doxycycline 40 mg modified-release capsules versus topical ivermectin 1% cream and placebo in the treatment of severe rosacea. j am acad dermatol. may 2019. [epub ahead of print] objective the objective of this post-hoc analysis was to extend beyond the phase 4 study looking at the efficacy and safety of ivermectin 1% cream (ivm) and doxycycline 40 mg modified release (dmr) in severe rosacea subjects, and highlight the impact on the visible and nonvisible symptoms associated with rosacea. the relationship between the following parameters was assessed: • impact of changes in the visible and nonvisible symptoms of rosacea on dermatology life quality index (dlqi) • impact of baseline lesion count, prior rosacea treatment, and disease duration on efficacy of combination therapy methods the study was a 12-week, multicenter, randomized, investigator-blinded, parallel-group comparative study in 273 adults with severe rosacea, as previously described (clinicaltrials.gov number: nct03075891).4 post-hoc analyses assessed the correlations between change in visible symptoms, stinging/burning, flushing severity, and dermatology life quality index (dlqi) and impact on disease burden using the spearman's rank correlation coefficient, mann–whitney u test, chi-square test, or kruskal–wallis test. analyses were performed on the combined treatment arms. results • impact of stinging/burning and ‘clear’ vs ‘almost clear’ on dlqi • a significant correlation was seen between change in stinging/burning over 12 weeks and change in dlqi score over 12 weeks (0.325; p =.000). [figures 1a–b] • significant correlations between the reduction in stinging/burning and individual dlqi parameters were found for itchy, painful skin (0.338; p =.000), problems with partner/friends (0.247; p =.000), feeling embarrassed (0.243; p=.000), and social activities (0.237; p =.000). [figure 1c] • significant correlations between ‘clear’ or ‘almost clear’ and individual dlqi parameters were found for feeling embarrassed (0.253; p =.000), interference with shopping/home garden (-0.161; p =.012), and social activities (-0.143; p=.026). [figure 1d] • severity of flushing and impact on dlqi • there was a significant correlation between change in flushing severity over 12 weeks and dlqi change over 12 weeks (0.222; p=.001). [figure 2] • impact of baseline lesion count, previous oral and/or topical treatment, and disease duration on efficacy of combination therapy • at week 12, there was a significant and strong correlation (-0.727; p=.000) between lesion counts at baseline and absolute change in lesion counts for the combined treatment arms. [figures 3 a–c] • in the combination therapy arm, the highest significant percent reduction in lesion count was observed for previous oral plus topical treatment (p=.016). [figure 4] • disease duration for up to 9 years was significantly correlated with highest percent change in lesion counts from baseline to week 12 in the combination therapy arm (p=.006). [figure 5] impact of reaching ‘clear ’ and ‘almost clear ’ on dlqi figure 1: d) spearmanʼs correlation between individual dlqi parameters and completely/almost clear by iga (the three parameters with the strongest correlations are shown) iga score at 12 weeks (locf) -0.253 0.000 243 correlation coefficient how embarrassed or self-conscious have you been because of your skin? p-value n -0.161 0.012 243 correlation coefficienthow much has your skin interfered with you going shopping or looking after your home or garden? p-value n -0.143 0.026 243 correlation coefficient how much has your skin affected any social or leisure activities? p-value n analyses were performed on the combined treatment arms. impact of reduction in stinging/burning on dlqi figure 1: a) change in dlqi score over 12 weeks versus change in stinging/burning score over 12 weeks in treatment groups combined. b) spearmanʼs correlation for the change in dlqi score versus change in stinging/burning score in treatment arms combined. c) spearmanʼs correlation between individual dlqi parameters and stinging/burning (the four parameters with strongest correlations are shown) 10 0 -10 -20 -30 -3 -2 -1 0 1 2 235 211 199 17 189 188 change in stinging/burning over 12 weeks (locf) ch an ge in d lq i s co re o ve r 1 2 w ee ks b) a) c) change in dlqi score over 12 weeks 0.325 0.000 243 correlation coefficient change in stinging/burning class over 12 weeks (locf) p-value n change in stinging/burning over 12 weeks (locf) 0.338 0.000 243 correlation coefficient change in how itchy, sore, painful, or stinging has your skin been? p-value n 0.247 0.000 243 correlation coefficientchange in how much has your skin created problems with your partner or any of your close friends or relatives? p-value n 0.243 0.000 243 correlation coefficient change in how embarrassed or self-conscious have you been because of your skin? p-value n 0.237 0.000 243 correlation coefficient change in how much has your skin affected any social or leisure activities? p-value n analyses were performed on the combined treatment arms. impact of reduction in severity of flushing and dlqi figure 2: spearmanʼs correlation of flushing severity with dlqi change in dlqi score over 12 weeks 0.222 0.001 216 correlation coefficient change in flushing severity class over 12 weeks (locf) p-value n impact of prior rosacea treatment on efficacy of combination therapy impact of disease duration on efficacy of combination therapy figure 4: association between oral versus topical previous treatment and percentage change in lesion count from baseline to week 12 investigated by kruskal–wallis test in the individual treatment arms and in the treatment arms combined figure 5: association between disease duration and percentage change in lesion count from baseline to week 12 investigated by kruskal–wallis test percentage change in lesion count from baseline to week 12 (locf) treatment 8.273 2 0.016 chi-square ivm+dmr df asymp. sig. percentage change in lesion count from baseline to week 12 (locf) treatment 10.266 2 0.006 chi-square ivm+dmr df asymp. sig. percentage change in lesion count from baseline to week 12 (locf) treatment mean nduration of rosacea standard deviation ivm+dmr -75.60–4 years 46 22.4 -86.55–9 years 39 17.8 -79.8≥10 years 50 22.9 -80.3total 135 21.7 percentage change in lesion count from baseline to week 12 (locf) treatment mean noral, topical or both standard deviation ivm+dmr -75.9oral 6 17.6 -70.2topical 31 25.1 -84.8oral+topical 18 23.7 -75.6total 55 24.5 impact of baseline lesion count on efficacy of combination therapy figure 3: a) box plot of number of lesions at baseline versus absolute change in lesion count from baseline to week 12 for the treatment arms combined. association between number of lesions at baseline versus absolute change in lesion count from baseline to week 12 in the treatment arms combined examined by b) kruskal–wallis test and c) spearmanʼs correlation 25 0 -50 -25 -75 20–29 30–39 40–49 50–69 131 113 238 146 222 154 102 196 167 156 137 169 32194 number of lesions (papules+pustules) at baseline ab so lu te ch an ge in le si on co un ts ov er 1 2 w ee ks (l o cf ) treatment arms: ivm+dmr and ivm+placebo change in lesion counts over 12 weeks (locf) 138.206 3 0.000 chi-square df asymp. sig. number of lesions (papules+pustules) at baseline -0.727 0.000 273 correlation coefficient p-value n change in lesion counts over 12 weeks (locf) a) b) c) fig 6. subject visual symptom improvement from baseline to week 12 ivm+dmr therapy resulted in notable reduction in visible symptoms baseline iga=4; il=55; cea=2 week 12 iga=1; il=1; cea=1 d) soo.p-rd113322-14 steve midgley line skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 125 resident competition research article the global burden of skin and subcutaneous disease: a longitudinal analysis from the global burden of disease study from 1990-2017 rachel l. giesey, do1, sino mehrmal, do2, prabhdeep uppal, do, ms3,4, gregory r. delost, do5,6 1department of dermatology, university hospitals cleveland medical center, cleveland, oh 2department of internal medicine, alameda health system – highland hospital, oakland, ca 3department of emergency medicine, christiana care health system, newark, de 4department of family medicine, christiana care health system, newark, de 5apex dermatology and skin surgery center, mayfield heights, oh 6lake erie college of osteopathic medicine, erie, pa skin and subcutaneous diseases are highly prevalent and one of the greatest contributors to disease morbidity in the world. in 2013, they were the fourth largest cause of nonfatal disease burden worldwide and ranked 18th in the top global contributors to disease burden.1 that same year in the united states alone, one in four individuals across all ages were seen by a physician for at least a single skin condition.2 half of all skin conditions are associated with mortality, and on average, death from skin disease has been seen to occur five years younger (68.2 years) than the average age of death for all causes.2 abstract background: the global prevalence and disability of skin and subcutaneous diseases have grown annually in recent decades. large-scale epidemiologic data is useful for better characterization of skin disease to create more impactful and sustainable interventions. methods: we assessed multiple global trends in skin and subcutaneous disease from 1990 to 2017 in 195 countries worldwide through the latest global burden of disease study results from 2017. results: skin and subcutaneous disease grew 46.8% between 1990 to 2017 and is ranked fourth by incidence of all causes of disease. there is global variation in disease burden when stratified by age, sex, geographic regions, and sociodemographic index. many global regions experience disproportionately elevated disease burden from certain subcategories of skin and subcutaneous disease. wealthier countries generally experienced the highest age-standardized disability rates of skin and subcutaneous disease. conclusion: the incidence, prevalence, and disability of skin and subcutaneous diseases are increasing disproportionately among countries and sociodemographic groups. this data may improve our understanding of skin and subcutaneous diseases to direct funding and resources to reduce global disparities. introduction skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 126 skin and subcutaneous diseases involve the global interaction of a variety of factors that impact regional disease morbidity. analyzing these trends on a large scale may improve our understanding of the risk factors and characteristics of skin and subcutaneous diseases to direct funding and resources to reduce global disparities through more impactful and sustainable interventions. one measurement of disease morbidity is disability-adjusted life years (dalys), measured as years of life lost due to premature mortality in the population plus the years lost due to disability (yld) for people living with a health condition or its consequences.3,4 furthermore, the sociodemographic index (sdi) was developed in 2016 to track key measures of socioeconomic development, predict health outcomes, monitor inequalities, and monitor the impact of interventions on health outcomes such as dalys.5,6 the sdi combines income per capita, years of schooling, and total fertility rate (tfr) to identify where countries sit on a spectrum of development on a scale of zero to one.5 the tfr is a summary measure of the average number of children a woman would deliver over her lifetime.5 one represents the highest possible income per capita, greatest average number of years of schooling, and lowest tfr.5 these metrics are useful in helping dermatologists and public health officials formulate and endorse data driven public health policies and guidelines to reduce the global burden of skin and subcutaneous disease. in this study, we show epidemiological data and multiple global trends in skin and subcutaneous disease. all results are derived from the global burden of disease (gbd) database. we also provide various indicators of global skin and subcutaneous disease disability and how they relate to age, geographic regions of the world, and sdi. other studies exist describing the global burden of skin and subcutaneous disease using 2010 and 2013 gbd study data.1,7 to our knowledge, there have been no further developments that include the most recent 2017 gbd study results. in addition, current gbd literature in skin and subcutaneous diseases have not yet addressed epidemiologic and disease burden trends as they relate to sdi. our study makes an important contribution to the growing and rapidly changing body of literature addressing global trends in the epidemiology and burden of skin and subcutaneous disease. our data was derived from publicly available gbd datasets from 2017. the gbd datasets provide data to compare the magnitude of diseases, injuries, and risk factors across age groups, sexes, countries, regions, and time from 1990 to the present day for over 350 diseases in 195 countries.5 a list of multiple disease etiologies measured by the gbd (e.g. skin and subcutaneous disease, cardiovascular diseases, neoplasms) with their corresponding global yld rank and percent change from 1990 to 2017 is provided (table 1). a similar table was created listing disease etiologies by global incidence rank along with their corresponding percent change from 1990 to 2017 (table 2). we provided a world map of the percent change in age-standardized prevalence rate of skin and subcutaneous disease per 100,000 population by country from 1990 to 2017 (figure 6). global prevalence metrics for ages ranging from age 0 to 95+ and the sex categories male and female were also provided for skin and subcutaneous disease methods skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 127 table 1: years lived with disability (yld) ranks when considering skin and subcutaneous disease collectively from 1990-2017. cause 2017 global ylds percent change (1990-2017) 2017 yld rank musculoskeletal disorders 135,881,239 66.0% 1 mental disorders 122,746,275 49.4% 2 neurological disorders 73,161,793 59.1% 3 sense organ diseases 66,576,077 76.2% 4 other non-communicable diseases 53,645,926 41.9% 5 diabetes & chronic kidney disease 45,844,350 117.5% 6 chronic respiratory diseases 44,311,836 49.7% 7 nutritional deficiencies 42,376,235 -15.5% 8 skin and subcutaneous diseases 41,621,861 40.2% 9 unintentional injuries 36,509,677 51.5% 10 cardiovascular diseases 35,697,253 87.7% 11 substance use disorders 31,052,753 56.6% 12 maternal & neonatal disorders 29,894,299 83.2% 13 digestive diseases 19,939,736 58.0% 14 neglected topical diseases & malaria 13,622,881 -8.1% 15 transport injuries 13,394,368 61.6% 16 respiratory infections & tuberculosis 11,670,255 27.6% 17 enteric injections 10,583,692 43.8% 18 neoplasms 7,775,158 124.0% 19 self-harm & violence 7,270,424 43.8% 20 hiv/aids & sexually transmitted infections 5,369,731 185.7% 21 other infectious diseases 4,056,632 4.4% 22 in 2017 (figure 1). when looking at the global morbidity of dermatoses as measured in dalys per 100,000 population in 2017, comparisons were made to age ranges (figure 2), and geographic regions of the world (figure 3). a comparison of global skin and subcutaneous disease change in dalys per 100,000 population between 1990 and 2017 is also given for the seven gbd super-regions along with the global average (figure 4). further comparisons were made between age-standardized dalys rates from dermatoses in all 195 countries surveyed by the gbd in 2017 with the respective sdi for each country (figure 5). across all disease categories measured by the gbd, skin and subcutaneous disease ranked ninth in 2017 when measured by yld, with an annual percent increase from 1990 to 2017 of 40.2% (table 1). when ranked by incidence, skin and subcutaneous disease ranked fourth with an annual percent increase of 46.8% between 1990 to 2017 (table 2). results skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 128 table 2: incidence ranks when considering skin and subcutaneous disease collectively from 1990-2017. cause number of new cases (1990-2017) percent change (1990-2017) 2017 incidence rank respiratory infections & tuberculosis 17,942,622,200 32.9% 1 enteric infections 6,307,792,414 51.6% 2 other non-communicable diseases 4,209,629,187 33.2% 3 skin and subcutaneous diseases 4,185,971,292 46.8% 4 nutritional deficiencies 1,186,745,815 32.5% 5 neurological disorders 1,006,294,496 46.2% 6 hiv/aids & sexually transmitted infections 769,111,205 42.1% 7 other infectious diseases 478,720,559 5.5% 8 digestive diseases 465,978,615 66.1% 9 unintentional injuries 415,410,278 47.9% 10 neglected topical diseases & malaria 357,652,091 29.4% 11 mental disorders 336,996,264 46.1% 12 musculoskeletal disorders 334,744,943 58.1% 13 maternal & neonatal disorders 101,960,798 6.7% 14 cardiovascular diseases 72,721,168 82.6% 15 transport injuries 63,920,593 57.4% 16 chronic respiratory diseases 62,161,350 26.0% 17 substance use disorders 60,099,555 44.2% 18 diabetes & chronic kidney disease 43,444,563 88.1% 19 self-harm & violence 41,379,417 27.2% 20 neoplasms 24,361,623 100.6% 21 many geographic clusters of the globe had an overall increase in skin and subcutaneous diseases including north america, the lower half of south america, western europe, eastern asia, and oceania (figure 6). not all countries exhibited increased prevalence, and many countries scattered throughout africa and southeast asia exhibited the greatest overall decrease in rates of dermatoses. females experience greater age-specific prevalence rates of skin disease on a global scale until about the age of 70, where the trend was seen to reverse with a slight male predominance (figure 1). skin and subcutaneous disease daly rates by age appear to have a bimodal distribution with peaks between 0 to 18 years of age and past 65 years of age (figure 2). most skin disease disability during infancy was seen between 28 to 364 days of age. a large peak in the combined daly rates of all dermatoses is seen immediately after infancy between 1 to 4 years of age, with an overall decrease in morbidity until 35 to 39 years of age before disease burden continues to increase up to 95+ years of age. skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 129 figure 1. age patterns by sex in 2017 of the total number of prevalent cases and age-specific prevalence rate of skin and subcutaneous diseases at the global level. the world regions with the greatest daly rates in 2017 included high-income north america, western europe, and australasia, while the lowest daly rates were seen in central asia, north africa and the middle east, and central europe (figure 3). three of the seven gbd super-regions (“highincome,” “sub-saharan africa,” and “latin american and caribbean”) exhibited greater dalys per 100,000 population than the combined global average of all regions (figure 4). a cluster of high sdi with high age-standardized daly rates could be seen when comparing age-standardized daly rates from skin and subcutaneous disease by country and sdi (figure 5). generally, a wide variation in age-standardized daly rates could be seen for other countries along the middle and lower ends of the sdi spectrum. both the global prevalence and associated dalys of skin and subcutaneous disease have grown in recent decades. the global prevalence of all skin disease was 26.79% in 2017, up from 26.15% in 1990, while the percentage of total dalys due to skin and subcutaneous diseases was 1.76% in 2017, up from 1.21% in 1990.9 the top three most prevalent dermatoses were fungal skin diseases (10.09%); “other skin conditions” encompassing skin diseases such as bullous diseases, connective tissue diseases, and cutaneous drug reactions discussion skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 130 figure 2. skin and subcutaneous disease daly rate per 100,000 at the global level by age, 2017. (7.47%); and atopic dermatitis (2.79%).9,10 the top three most disabling dermatoses as measured in dalys were atopic dermatitis (0.36%), psoriasis (0.22%), and urticaria (0.20%).9 a few easily treated or preventable dermatoses including fungal skin disease, dermatitis (atopic, contact and seborrheic), and scabies have a disproportionately high loss of productivity and income.10 the gbd study diagnoses are arranged according to the international classification of diseases (icd) system, leading to many dermatologic conditions or manifestations grouped in entirely separate disease categories outside the scope of this study.11 for example, melanoma and nonmelanoma skin cancer (nmsc) are grouped as “neoplasms”, and the entire burden of lupus erythematosus is found in “other musculoskeletal diseases".7 multiple trends regarding the age and sex distribution of skin and subcutaneous diseases have been described. infants are commonly affected by dermatitis and skin infections; atopic dermatitis is the most common skin disease in children, especially in developed countries, before gradually decreasing with increased age.12 viral warts caused by human papillomavirus ranks skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 131 figure 3. skin and subcutaneous disease daly rate per 100,000 by gbd world regions, 2017. second in children.13 similarly, children in developing countries also generally have high levels of viral warts before prevalence peaks in adolescence and generally resolves by age 16.14 children in developing countries also have greater prevalence of fungal infections such as tinea capitis.15 in elderly populations, there is a general predisposition to dermatitis and pressure ulcers due to degenerative skin changes.16 pressure ulcers affect approximately 25% of the population over the age of 70 and are associated with decreased quality of life, increased rates of disability, and higher treatment costs.17 seborrheic dermatitis prevalence in this population has a male predisposition and may be as high as 31%, leading to significant distress from pruritus that worsens in the winter.16 by 2050, 80% of older populations will be living in lowand middle-income countries.18 as the elderly population and corresponding rates of skin and subcutaneous disease continue to grow, an emphasis on primary prevention may serve dual functions of lowering disease burden and serving as a cost-effective intervention for lower income populations. wide geographic variation is also characteristic of many skin and subcutaneous diseases and may be attributed to a variety of factors. for example, there appears to be some association in the prevalence of psoriasis and country distance from the equator.19 however, the geographic variation of psoriasis remains poorly understood and may be due to a combination of climate, genetics, and environmental factors such as antigen exposure and vitamin d levels.19 skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 132 figure 4. trends from 1990 to 2017 in dalys per 100,000 rates of skin and subcutaneous skin diseases in seven gbd super-regions along with the global value. geopolitical factors like armed conflict may lead to crowding in refugee camps, thus promoting the spread of transmissible diseases like scabies.20 climate change may also promote variable burden of bacteria, viruses, fungi, and parasites, leading to spread of previously endemic skin diseases beyond their traditional geographic borders.21 socioeconomic factors also affect disease burden as they may dictate the availability and quality of available diagnostics and treatments. high sdi countries were seen to have high levels of inflammatory dermatoses such as atopic dermatitis and psoriasis. in the case of atopic dermatitis, the hygiene hypothesis has attempted to describe the trend of industrialized countries having higher levels of atopic conditions.22 the lack of microbial burden from improved living conditions, antibiotic use, and childhood vaccinations have been seen to promote atypical immune responses.22 the risk may be increased further by environmental factors such as increased particle air pollution from motor skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 133 figure 5. age-standardized dalys rates from skin and subcutaneous by socio-demographic index (sdi) for all 195 countries and territories in 2017. expected values are shown as the black line. vehicles or second-hand smoke indoors.23 there is little data correlating psoriasis with the socioeconomic status of countries, but studies have shown a significant association between poor control of psoriasis and lower educational attainment.24,25 part of the high disease burden in more affluent countries may also be attributed to increased data collection from easier access to physician led specialty care and high sensitivity diagnostics.2,26 though outside the scope of gbd estimates of skin and subcutaneous disease, high skin cancer burden in high sdi populations is a well-studied phenomenon and is a major example of high socioeconomic status driving high disease burden. in the case of skin cancer, high socioeconomic populations are predisposed to increased exposures to occupational chemicals and greater ultraviolet radiation exposure due to easier access to indoor tanning, social pressures of skin appearance, and increased holiday travel.27 skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 134 figure 6. percent change in age-standardized prevalence rate of skin and subcutaneous disease per 100,000 population from 1990 to 2017. the top ten countries with the largest increase were: singapore, south korea, ireland, spain, malta, cyprus, chile, austria, luxembourg, and portugal. the top ten countries with largest decrease were: bangladesh, rwanda, bhutan, mali, burundi, nepal, eritrea, equatorial guinea, comoros, and burkina faso. at the middle and low ends of the sdi spectrum, countries were seen to have higher disease burden from dermatologyrelated infectious diseases including scabies and fungal diseases. high scabies disease burden has been seen in hot, tropical areas as well as overcrowded regions, which may result from armed conflict or natural disaster.20 high household density has been shown to be a more important contributor to transmissible skin disease than salary, literacy, shoe use, distance to a water source, and quality of home construction.28 unfortunately, there is little high-quality research on the socioeconomic burden of skin disease in resource-poor settings. lack of public education and resources may also continue to account for the large number of people continuing to live with disabling skin conditions in these areas, in addition to the lack of physician-led dermatologic care in many low and middle income countries.11,29 the lack of research in these regions often leads to extrapolation of findings from high income countries as these countries are often the leaders in shaping global health policies.11 unfortunately, such findings are not always relevant to or feasible in resource poor populations and settings. recent estimates of total health care costs of skin disease in the united states were $75 billion, with per capita costs of $240 annually.2 these costs are mitigated by relatively high individual spending power and well developed health systems. indirect opportunity costs such as missing work are also relatively easier to cope with in high sdi countries. unfortunately, these are not the features or characteristics of resourcepoor populations and settings. cost-effective strategies have been described to help bridge such disparities and improve quality of care in resource-poor settings including teledermatology, development of point-ofcare diagnostics, and education of lay persons by experienced providers.11 however, increased funding and research is skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 135 required to account for the different financial, geographic, and cultural variations in resource-poor settings as they relate to skin and subcutaneous disease.11 there are limitations when considering the global burden of skin and subcutaneous diseases. as mentioned previously, some dermatologic conditions or manifestations (e.g. melanoma, nmsc, and lupus erythematosus) fall outside the scope of this study as their icd classifications place them in categories entirely separate from skin and subcutaneous disease, which likely underestimates the true burden of skin disease.7,11 disability estimates may also only reflect symptoms such as itch and appearance changes and may lack the inclusion of complications such as secondary infection or mental health impact.1,11 there may also be limitations in geographic diversity where certain populations have a relative excess or scarcity of studies in relation to their total population, which may lead to filling of data gaps through statistical modeling. additionally, patients may be reluctant to report skin conditions as is commonly seen with the social stigmatization associated with psoriasis, leading to underestimation of disease burden.30 despite the limitations inherent to the gbd and the global reporting of the burden of dermatoses, large scale epidemiological data continues to help dermatologists and key policy and decision makers shape public health policies and better understand skin disease. dermatologists will continue to face challenges as they strive to reduce the global burden of skin and subcutaneous diseases. an emphasis on community engagement, outreach, and prevention may lead to more sustainable interventions with greater public health impact. as the growth of our elderly populations outpaces that of other ages, we must be especially cognizant of this vulnerable group with high skin disease burden. we must also keep the accessibility and finances of future interventions in mind to determine their global relevance and feasibility. increased funding, collaboration with other specialties and health professionals in the care of dermatoses and their comorbidities, and development of new therapies are promising steps to overcome the challenge of reducing the global burden of skin and subcutaneous diseases. abbreviations: dalys – disability adjusted life years gbd – global burden of disease study icd – international classification of diseases nmsc – non-melanoma skin cancer sdi – socio-demographic index tfr – total fertility rate conflict of interest disclosures: the authors have no conflict of interest to declare. this research has been conducted as part of the global burden of diseases, injuries, and risk factors study (gbd), coordinated by the institute for health metrics and evaluation. all authors are collaborators with the global burden of disease. this article was not developed with consultation or support with the global burden of disease research team. funding: the gbd was partially funded by the bill & melinda gates foundation; the funders had no role in the study design, data analysis, data interpretation, or writing of the report. corresponding author: rachel giesey, do department of dermatology university hospitals cleveland medical center 11100 euclid avenue lakeside 3500 cleveland, oh 44106 phone: 330-592-6091 fax: 216-844-8993 email: rachel.giesey2@uhhospitals.org conclusion skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 136 references: 1. karimkhani c, dellavalle rp, coffeng le, et al. global skin disease morbidity and mortality: an update from the global burden of disease study 2013. jama dermatol. 2017;153(5):406-412. 2. lim hw, collins sab, resneck js, et al. the burden of skin disease in the united states. j am acad dermatol. 2017;76(5):958-972.e952. 3. metrics: disability-adjusted life year (daly). world health organization. https://www.who.int/healthinfo/global_burden_disease/ metrics_daly/en/. accessed march 26, 2020. 4. organization wh. health statistics and information systems. https://www.who.int/healthinfo/global_burden_disease/ metrics_daly/en/. accessed may 26, 2020. 5. frequently asked questions. ihme. http://www.healthdata.org/gbd/faq. accessed may 26, 2020. 6. leach-kemon k. a new way of measuring development helps assess health system performance. ihme. http://www.healthdata.org/actingdata/new-way-measuring-development-helps-assesshealth-system-performance. published 2017. accessed may 26, 2020. 7. hay rj, johns ne, williams hc, et al. the global burden of skin disease in 2010: an analysis of the prevalence and impact of skin conditions. j invest dermatol. 2014;134(6):1527-1534. 8. protocol for the global burden of diseases, injuries, and risk factors study (gbd). in: institute for health metrics and evaluation; 2018. 9. network gbodc. global burden of disease study 2017 results. in: evaluation ifhma, ed. seattle, united states: global burden of disease collaborative network. ; 2018. 10. mehrmal s, uppal p, giesey rl, delost gr. identifying the prevalence and disability-adjusted life years of the most common dermatoses worldwide. j am acad dermatol. 2020;82(1):258-259. 11. seth d, cheldize k, brown d, freeman ef. global burden of skin disease: inequities and innovations. curr dermatol rep. 2017;6(3):204-210. 12. vakirlis e, theodosiou g, apalla z, et al. a retrospective epidemiological study of skin diseases among pediatric population attending a tertiary dermatology referral center in northern greece. clin cosmet investig dermatol. 2017;10:99-104. 13. nanda a, al-hasawi f, alsaleh qa. a prospective survey of pediatric dermatology clinic patients in kuwait: an analysis of 10,000 cases. pediatr dermatol. 1999;16(1):6-11. 14. sladden mj, johnston ga. common skin infections in children. bmj. 2004;329(7457):95-99. 15. kiprono sk, muchunu jw, masenga je. skin diseases in pediatric patients attending a tertiary dermatology hospital in northern tanzania: a cross-sectional study. bmc dermatol. 2015;15:16. 16. farage ma, miller kw, berardesca e, maibach hi. clinical implications of aging skin: cutaneous disorders in the elderly. am j clin dermatol. 2009;10(2):73-86. 17. rasero l, simonetti m, falciani f, fabbri c, collini f, dal molin a. pressure ulcers in older adults: a prevalence study. adv skin wound care. 2015;28(10):461-464. 18. ageing and health. world health organization. https://www.who.int/news-room/factsheets/detail/ageing-and-health. published 2018. accessed may 26, 2020. 19. griffiths cem, van der walt jm, ashcroft dm, et al. the global state of psoriasis disease epidemiology: a workshop report. br j dermatol. 2017;177(1):e4-e7. 20. karimkhani c, colombara dv, drucker am, et al. the global burden of scabies: a cross-sectional analysis from the global burden of disease study 2015. lancet infect dis. 2017;17(12):1247-1254. 21. kaffenberger bh, shetlar d, norton sa, rosenbach m. the effect of climate change on skin disease in north america. j am acad dermatol. 2017;76(1):140-147. 22. okada h, kuhn c, feillet h, bach jf. the 'hygiene hypothesis' for autoimmune and allergic diseases: an update. clin exp immunol. 2010;160(1):1-9. 23. venn aj, yemaneberhan h, bekele z, lewis sa, parry e, britton j. increased risk of allergy associated with the use of kerosene fuel in the home. am j respir crit care med. 2001;164(9):1660-1664. 24. kimball ab, augustin m, gordon kb, et al. correlation of psoriasis activity with socioeconomic status: crosssectional analysis of patients enrolled in the psoriasis longitudinal assessment and registry (psolar). br j dermatol. 2018;179(4):984-986. 25. mahé e, beauchet a, reguiai z, et al. socioeconomic inequalities and severity of plaque psoriasis at a first consultation in dermatology centers. acta derm venereol. 2017;97(5):632-638. 26. apalla z, lallas a, sotiriou e, lazaridou e, ioannides d. epidemiological trends in skin cancer. dermatol pract concept. 2017;7(2):1-6. 27. brouse ch, hillyer gc, basch ce, neugut ai. geography, facilities, and promotional strategies used to encourage indoor tanning in new york city. j community health. 2011;36(4):635-639. 28. gibbs s. skin disease and socioeconomic conditions in rural africa: tanzania. int j dermatol. 1996;35(9):633-639. 29. tsang mw, kovarik cl. the role of dermatopathology in conjunction with teledermatology in resource-limited settings: lessons from the african teledermatology project. int j dermatol. 2011;50(2):150-156. 30. michalek im, loring b, john sm, world health organization. global report on psoriasis. geneva, switzerland: world health organization; 2016. improvements in lesional pain and itch symptoms with brodalumab in psoriasis studies lawrence f. eichenfield,1 april armstrong,2 lawrence green,3 shipra rastogi,4 radhakrishnan pillai,5 robert israel6 1university of california, san diego, ca; 2university of southern california, los angeles, ca; 3george washington university school of medicine, washington, dc; 4ortho dermatologics, bridgewater, nj; 5dow pharmaceutical sciences (a division of valeant pharmaceuticals north america llc), petaluma, ca; 6valeant pharmaceuticals north america llc, bridgewater, nj 2017 fall clinical dermatology conference® • october 12-15, 2017 • las vegas, nv introduction • the interleukin-17 receptor a (il-17ra) antagonist brodalumab has demonstrated efficacy and safety for the treatment of moderate-to-severe plaque psoriasis in phase 3 clinical studies1,2 – amagine-1: adult patients were randomized to receive placebo, brodalumab 140 mg, or brodalumab 210 mg every 2 weeks (q2w)1 – amagine-2/-3: patients were randomized to receive placebo, brodalumab (140 or 210 mg q2w), or ustekinumab (45 or 90 mg depending on body weight)2 – brodalumab demonstrated superior efficacy at week 12 vs placebo and ustekinumab amagine-1: brodalumab 140 mg q2w and 210 mg q2w vs placebo as measured by static physician’s global assessment (spga) success (0 or 1) and psoriasis area and severity index (pasi) 75 amagine-2/-3: brodalumab 210 mg q2w vs ustekinumab as measured by pasi 100 – the most common adverse events across the 3 trials included nasopharyngitis, upper respiratory tract infections, and headache1,2 • the psoriasis symptom inventory (psi) is a validated, 8-item, patient-reported outcome instrument designed to assess pain, itch, cracking, scaling, redness, flaking, burning, and stinging in psoriasis3-5 – the psi assesses signs and symptoms that contribute to disease burden and are considered key measures of patient improvement3 – two items assessed by the psi, pain and itch, have been identified by patients as separate psoriasis symptoms that may contribute to diminished health-related quality of life3 – itch is of particular interest because the itch-scratch cycle can increase inflammation, intensify original itch, traumatize skin, and expand psoriatic lesions through koebnerization6 objective • the effect of brodalumab on lesional pain and itch, as measured within the psi, was assessed in patients with moderate-to-severe psoriasis from three phase 3, multicenter, randomized, double-blind, placeboand active-comparator– controlled studies (amagine-1/-2/-3) methods procedures • patients in the amagine-1/-2/-3 studies were randomized to receive treatment during the 12-week induction phase as follows: amagine-1: brodalumab (140 or 210 mg q2w) or placebo; amagine-2: brodalumab (140 or 210 mg q2w), placebo, or ustekinumab; amagine-3: brodalumab (140 or 210 mg q2w), placebo, or ustekinumab • patients used a daily electronic diary to rate the severity of symptoms during the previous 24 hours on a psi scale of 0 (not at all severe) to 4 (very severe) – in addition to visual assessments of redness, scaling, cracking, and flaking symptoms, which were also included in pasi and spga evaluations, the psi assessed pain, itch, burning, and stinging symptoms statistical analysis • daily assessments of pain and itch symptoms were analyzed as weekly psi item average scores. at each study visit (including the baseline assessment), the psi responder status of patients was assessed; a responder for the pain and itch items was defined as having a weekly psi item average score ≤1 • statistical comparisons were based on cochran-mantel-haenszel or analysis of covariance models stratified by total body weight at baseline (≤100 kg, >100 kg), prior biologic use (yes, no), geographic region, study, and adjusting for baseline psi score (≤ median, > median). there was no adjustment for multiplicity results patient demographics • baseline demographics and disease characteristics, including mean overall psi scores, were similar across treatment groups (table 1) mean psi item scores for pain and itch • at baseline, average pain and itch scores were comparable between placebotreated and brodalumab-treated patients (table 2) – at week 1, mean scores (standard deviation [sd]) for symptoms of pain (placebo, 1.9 [1.1]; brodalumab 140 mg q2w, 1.6 [1.1]; brodalumab 210 mg q2w, 1.5 [1.1]) and itch (placebo, 2.5 [0.9]; brodalumab 140 mg q2w, 2.2 [0.9]; brodalumab 210 mg q2w, 2.2 [0.9]) were significantly lower with both doses of brodalumab vs placebo (all p<0.001) • mean pain and itch scores remained significantly lower with brodalumab vs placebo through week 12 (table 2 and figure 1) psi item responders • at baseline, the percentages of patients with pain and itch with an average weekly score ≤1 (classified as responders) were 24.2% and 5.5%, respectively, for the placebo group, 23.4% and 6.7% for the brodalumab 140-mg group, and 23.4% and 6.2% for the brodalumab 210-mg group, respectively – at week 1, the proportion of responders for pain and itch had significantly increased from baseline with both doses of brodalumab vs placebo pain: placebo, 25.4%; 140 mg q2w, 34.9% (p<0.0001); 210 mg q2w, 37.4% (p<0.0001) itch: placebo, 5.8%; 140 mg q2w, 10.4% (p=0.0002); 210 mg q2w, 11.9% (p<0.0001) – at week 12, for both pain and itch, a significantly greater proportion of patients treated with either dose of brodalumab vs placebo were psi item responders (figure 2) pain and itch response over time • in amagine-1/-2/-3, percentage-point increases from baseline for pain and itch at week 12 were 9.3% and 7.7% for the placebo group, 47.7% and 54.1% for the brodalumab 140-mg q2w group, and 55.1% and 65.1% for the brodalumab 210-mg group, respectively (all p<0.0001 vs placebo) • in a combined analysis of the two phase 3 studies with ustekinumab as the active comparator (amagine-2/-3), treatment with brodalumab demonstrated rapid and significant improvement vs ustekinumab starting with week 1 for pain (ustekinumab, 31.3%; brodalumab 140 mg q2w, 35.8% [p=0.0207]; brodalumab 210 mg q2w, 38.3% [p=0.0007]) and with week 2 for itch (ustekinumab, 17.1%; brodalumab 140 mg q2w, 30.9% [p<0.0001]; brodalumab 210 mg q2w, 36.4% [p<0.0001]; figure 3) – significant treatment differences in response rates were observed with brodalumab 210 mg q2w vs ustekinumab through week 10 for pain (p<0.01) and week 12 for itch (p<0.01; figure 3) table 2. summary of psi item scores (as observed) by treatment group at baseline and week 12 in amagine-1/-2/-3 table 1. patient baseline demographics and clinical characteristics (integrated amagine-1/-2/-3 induction phase analysis set) amagine-1/-2/-3 pain amagine-1/-2/-3 itch r es po nd er , % 60 0 40 20 80 100 33.5 283/844 1036/1458 1145/1458 n 111/844 887/1458 1040/1458 n *** 71.1 a *** 78.5 placebo 140 mg q2w 210 mg q2w brodalumab r es po nd er , % 60 0 40 20 80 100 13.2 *** 60.8 b *** 71.3 placebo 140 mg q2w 210 mg q2w brodalumab figure 2. percentage of psi item responders for symptoms of (a) pain and (b) itch in patients treated with brodalumab (140 or 210 mg q2w) or placebo at week 12 in phase 3 studies. figure 1. percent improvement from baseline in observed psi item mean scores at week 12 in symptoms of (a) pain and (b) itch in patients treated with brodalumab (140 or 210 mg q2w) or placebo at week 12. im pr ov em en t fr om b as el in e, % 60 0 40 20 80 100 10.0 762 1312 1309 n 762 1312 1309 n 70.0 a 81.0 placebo 140 mg q2w 210 mg q2w brodalumab amagine-1/-2/-3 pain amagine-1/-2/-3 itch im pr ov em en t fr om b as el in e, % 60 0 40 20 80 100 3.8 61.5 b 72.0 placebo 140 mg q2w 210 mg q2w brodalumab psi, psoriasis symptom inventory; q2w, every 2 weeks. acknowledgments: medical writing support was provided by anthony hutchinson, phd, medthink scicom, and funded by ortho dermatologics. these studies were sponsored by amgen inc. references: 1. papp ka, reich k, blauvelt a, et al. br j dermatol. 2016;175(2):273-286. 2. lebwohl m, strober b, menter a, et al. n engl j med. 2015;373(14):1318-1328. 3. martin ml, mccarrier kp, chiou cf, et al. j dermatolog treat. 2013;24(4):255-260. 4. bushnell dm, martin ml, mccarrier k, et al. j dermatolog treat. 2013;24(5):356-360. 5. revicki da, jin y, wilson hd, chau d, viswanathan hn. j dermatolog treat. 2014;25(1):8-14. 6. dawn a, yosipovitch g. dermatol nurs. 2006;18(3):227-233. conclusions • brodalumab demonstrated significant improvement in patient-reported pain and itch symptoms of psoriasis vs placebo and ustekinumab, as measured by the psi, in three phase 3 controlled clinical trials – significant improvement in pain was observed at week 1 and persisted through week 10 in patients treated with brodalumab 210 mg q2w compared with ustekinumab – significant improvement in itch was observed at week 2 and persisted through week 12 in patients treated with brodalumab 210 mg q2w compared with ustekinumab brodalumab placebo (n=844) 140 mg q2w (n=1458) 210 mg q2w (n=1458) age, mean (sd), y 44.7 (12.9) 44.8 (13.0) 45.1 (12.9) male, n (%) 588 (69.7) 1012 (69.4) 1013 (69.5) white, n (%) 769 (91.1) 1322 (90.7) 1319 (90.5) weight, mean (sd), kg 90.2 (22.0) 90.4 (21.6) 90.7 (23.1) body mass index, mean (sd), kg/m2 30.2 (6.8) 30.4 (7.0) 30.5 (7.3) duration of psoriasis, mean (sd), y 18.5 (12.0) 18.1 (11.9) 18.7 (12.4) psoriatic arthritis (yes), n (%) 173 (20.5) 319 (21.9) 299 (20.5) bsa, mean (sd), % 27.6 (17.1) 27.8 (17.8) 26.8 (16.8) pasi score, mean (sd) 20.1 (8.2) 20.2 (8.2) 20.2 (8.0) spga score, n (%) 3 4 5 (very severe) 473 (56.0) 324 (38.4) 47 (5.6) 899 (61.7) 489 (33.5) 70 (4.8) 810 (55.6) 567 (38.9) 81 (5.6) psi score, mean (sd) 18.8 (6.9) 18.7 (7.1) 18.7 (7.0) prior biologic therapy (yes), n (%) 267 (31.6) 438 (30.0) 439 (30.1) bsa, psoriasis body surface area involvement; pasi, psoriasis area and severity index; psi, psoriasis symptom inventory; q2w, every 2 weeks; sd, standard deviation; spga, static physician’s global assessment. brodalumab psi item placebo (n=844)a 140 mg q2w (n=1458)a 210 mg q2w (n=1458)a pain mean baseline score (sd) mean score at week 12 (sd) ls mean treatment difference vs placebo (95% ci) p value 2.0 (1.2) 1.8 (1.3) 2.0 (1.2) 0.6 (1.0) -1.1 (-1.2, -1.0) <0.001 2.1 (1.2) 0.4 (0.8) -1.3 (-1.4, -1.3) <0.001 itch mean baseline score (sd) mean score at week 12 (sd) ls mean treatment difference vs placebo (95% ci) p value 2.6 (0.9) 2.5 (1.1) 2.6 (0.9) 1.0 (1.1) -1.4 (-1.5, -1.3) <0.001 2.5 (0.9) 0.7 (0.9) -1.7 (-1.8, -1.6) <0.001 ci, confidence interval; ls, least squares; psi, psoriasis symptom inventory; q2w, every 2 weeks; sd, standard deviation. anumber of patients at baseline. at baseline, the number of evaluable patients was as follows: placebo, n=790; brodalumab 140 mg q2w, n=1357; brodalumab 210 mg q2w, n=1368. at week 12, the number of evaluable patients was 762, 1312, and 1309, respectively. nonresponder imputation was used to impute missing data. psi item responders were defined as having a psi item weekly average score ≤1. psi, psoriasis symptom inventory; q2w, every 2 weeks. ***p<0.0001 vs placebo. ustekinumab (n=613) brodalumab 140 mg q2w (n=1239) brodalumab 210 mg q2w (n=1236) r es po nd er , % 60 0 40 20 80 100 a week 0 1 2 3 4 5 6 7 8 9 10 11 12 amagine-2/-3 pain ** **** *** *** ** *** *** *** *** *** *** **** *** * *** r es po nd er , % 60 0 40 20 80 100 b week 0 1 2 3 4 5 6 7 8 9 10 11 12 amagine-2/-3 itch *** ***** *** *** *** *** *** *** *** *** *** ***** *** *** ** figure 3. psi item response over time for symptoms of (a) pain and (b) itch in patients treated with brodalumab (140 or 210 mg q2w) or ustekinumab. shaded portion of figure highlights significant increase in responders observed with brodalumab vs ustekinumab at week 1 for pain and week 2 for itch. nonresponder imputation was used to impute missing data. psi, psoriasis symptom inventory; q2w, every 2 weeks. *p<0.05 vs ustekinumab. **p<0.01 vs ustekinumab. ***p<0.0001 vs ustekinumab. © 2017. all rights reserved. 7590_pain and itch (wcdc encore)_m1-3.indd 1 10/2/17 12:14 pm fc17postervaleanteichenfieldimprovementpainanditch.pdf compatibility of a colloidal oatmeal containing body wash for pediatric subjects with atopic dermatitis arrowitz cea, jiang lb, hino pdb, weber tma abeiersdorf inc., wilton, ct, usa. bthomas j. stephens & associates, inc., richardson, tx, usa. background: cleansing is an important part of regular hygiene, especially for patients with atopic dermatitis (ad) due to their susceptibility to skin infections. however, for these patients, regular cleansing with soaps and detergents can irritate their sensitive skin and exacerbate flares. current aad guidelines for the management of ad recommend use of non-soap cleansers that are low-ph, hypoallergenic, and fragrance-free. the following clinical trial tested a specially formulated mild cream body wash (mcbw) containing 2% colloidal oatmeal (skin protectant), mild surfactants, ceramide np, and components of the natural moisturizing factor on children with ad. the mcbw formula was further optimized for this population by its low ph, and fragrance-, dye-, and soap-free properties. aim: this clinical trial was conducted to test the tolerability of a mcbw when used for regular bathing (once daily) by children and young adults with clinically confirmed ad. method: study duration was 2 weeks with tolerability evaluations (clinical grading) and self-assessment questionnaires (completed by a parent/guardian when appropriate) conducted at baseline, week 1, and week 2 clinical visits. 35 male and female children, ages 2 months to 18 years old were included in the following three age bands: 2 months through 24 months n=10, 25 months through 12 years n=14, 13 years to 18 years n=11. subjects were instructed to use only the mcbw for their bathing routines. results: the mcbw was well tolerated by all subjects. statistically significant (p<0.001) reductions in clinically graded erythema, dryness, and itching were observed at weeks 1 and 2 compared to baseline (pre-cleanser use). additionally, significantly fewer subjects reported itching (p<0.05) and dryness (p<0.001) after bathing at weeks 1 and 2 compared to baseline. after 1 week of use, 91.4% of parents/guardians found that the cleanser was gentle on their child’s eczematic/eczema-prone skin, and 88.6% agreed the cleanser was gentle enough for everyday use. conclusion: mcbw was very well tolerated by pediatric subjects with clinically confirmed ad. the results demonstrate that the skin protectant body wash is well-suited for everyday use by subjects with ad, helping to reduce the irritation caused by regular bathing. • mild cream body wash was well tolerated • statistically significant reductions in erythema, dryness, and itching were observed at weeks 1 and 2 compared to baseline (pre-cleanser use) • a significant decrease in irritation parameters from bathing was observed with product use • subjects reported the cleanser to be gentle on their eczematic skin, and gentle enough for everyday use abstract conclusions research sponsored by beiersdorf inc. perception of tolerability (week 1) a baseline week 1 week 2 ** 0.43 ** 0.31 0.80 ** 0.86 ** 0.64 1.54 0 0 0.09 ** 0.37 ** 0.20 0.83 m e a n g ra d e erythema dryness burning itching **statistically significant compared to baseline (p<0.001) figure 1. tolerability grading: mean scores. tolerability evaluations for erythema, dryness, burning, and itching were conducted at baseline, week 1, and week 2 using a 0 to 3 scale (0=none to 3=severe). subjects (n=35) bathed daily utilizing the mild cream body wash as part of their bathing routine for two weeks. 1.8 1.6 1.4 1.2 1.0 0.8 0.6 0.4 0.2 0.0 tolerability grading 100% 80% 60% 40% 20% 0% % s u b je c ts figure 3. skin condition after bathing. self-assessments were conducted at baseline, week 1, and week 2 using a subject questionnaire. subjects (n=35) bathed daily utilizing the mild cream body wash as part of their bathing routine for two weeks. a. skin irritation after bathing; b. skin itches after bathing; c. skin feels dry after bathing; d. skin appears red after bathing. baseline week 1 week 2 agree disagree ** 62.9% 14.3% ** 71.4% 14.3% 28.6% 42.8% **statistically significant compared to baseline (p!0.001) 100% 80% 60% 40% 20% 0% % s u b je c ts baseline week 1 week 2 agree disagree ** 45.7% 40.0% 14.3% ** 74.3% 20.0% 80.0% **statistically significant compared to baseline (p!0.001) 100% 80% 60% 40% 20% 0% % s u b je c ts baseline week 1 week 2 agree disagree * 51.4% 34.3%37.2% * 62.9% 25.7% 50.0% *statistically significant compared to baseline (p!0.05) 100% 80% 60% 40% 20% 0% % s u b je c ts baseline week 1 week 2 agree disagree * 60.0% 25.7% 31.4% * 65.8% 17.2% 51.4% *statistically significant compared to baseline (p!0.05) my (child’s) skin feels dry after bathing my (child’s) skin itches after bathing my (child’s) skin is irritated after bathing my (child’s) skin appears red after bathing c b a d 2020 fall clinical dermatology conference b 91.4%** 5.7%** 74.3** 20% 88.6%** 11.4%** 94.3%** 5.8%** the cleanser is gentle on my (child’s) eczematic skin the cleanser is gentle during application the cleanser did not burn my (child’s) eczematic skin the cleanser is gentle enough to use every day agree disagree**statistically significant compared to baseline (p<0.001) week 1 0 20 40 60 80 100 88.5%** 5.8%** 82.9** 14.3% 85.8%** 8.6%** 91.5%** 5.7%** the cleanser is gentle on my (child’s) eczematic skin the cleanser is gentle during application the cleanser did not burn my (child’s) eczematic skin the cleanser is gentle enough to use every day 0 20 40 60 80 100 figure 2. perception of tolerability. self-assessments were conducted at week 1 and week 2 using a subject questionnaire. subjects (n=35) bathed daily utilizing the mild cream body wash as part of their bathing routine for two weeks. a. week 1; b. week 2. agree disagree**statistically significant compared to baseline (p<0.001) week 2 perception of tolerability (week 2) bookmarks skin march 2018 volume 2 issue 2 copyright 2018 the national society for cutaneous medicine 140 brief articles case report of a successful hair transplantation in a patient with lichen planopilaris/frontal fibrosing alopecia due to incidental chemotherapy for breast carcinoma allison l. limmer bs ba a , jennifer krejci-manwaring md b , bobby l. limmer md b a mcgovern medical school at uthealth, houston, tx b the university of texas health science center at san antonio, san antonio, tx a 67-year-old female presented to our office for hair loss evaluation in 2008. she noted progressive hair loss throughout her scalp but most pronounced at her hairline and crown. on exam, there were patches of scant hair growth with background scarring of the crown and mid-scalp with regression of the frontal hairline of approximately 3 cm. there was perifollicular scale and erythema at the crown and mid-scalp but most prominent along the frontal hairline. there were decreased vellus hairs in the crown and few at the hairline, but miniaturization was present in the mid-scalp. no photos were taken, but a biopsy was performed and consistent with late-stage lpp/ffa with a background of androgenetic alopecia. she underwent one treatment with intralesional triamcinolone 2.4 mg/ml x 20 ml to the frontal hairline and vertex scalp and was lost to follow-up. in 2009 the patient was diagnosed with breast carcinoma and underwent mastectomy and chemotherapy. she was treated with 9 cycles of doxorubicin, cyclophosphamide, and dexamethasone; some cycles included docetaxel. she returned for re-evaluation of her alopecia in 2010, 7 months after completion of chemotherapy. on examination, there was early regrowth of hair from chemotherapy abstract lichen planopilaris (lpp) and its variant frontal fibrosing alopecia (ffa) are disfiguring alopecias that rarely yield satisfactory hair transplantation results. grafts may grow initially only to be obliterated by re-activation of the disease within the first few months to years post-transplant. here, we detail the management of a patient who was diagnosed and treated for breast carcinoma after her diagnosis of lpp/ffa. two years after completion of chemotherapy, the patient presented with quiescence of her lpp and successfully underwent hair transplantation by follicular unit transplantation method. she has maintained the grafts without re-activation of her scarring alopecia for 7 years – a success we attribute to chemotherapy. case report skin march 2018 volume 2 issue 2 copyright 2018 the national society for cutaneous medicine 141 induced anagen effluvium but no erythema or perifollicular scale. conservative medical management with rogaine was recommended. repeat biopsy was not performed. at 1-year follow-up, her hair had recovered back to baseline, as her exam remained virtually unchanged from 2009: scarring alopecia measuring approximately 5 x 8 cm of the crown and 3 cm regression of the frontal hairline with no scale or erythema – no evidence of active lpp/ffa (figure 1a, b). the mid-scalp still demonstrated sparse coverage with features of androgenetic alopecia – diffuse thinning, variation in hair shaft caliber, and miniaturization. the rest of the patient’s hair shafts were noted to be “fine” in texture. notably, the patient continued to wear a wig daily since her chemotherapy-induced anagen effluvium. the patient elected to proceed to transplantation by follicular unit transplantation method (fut/strip), recognizing the potential for re-activation of her lpp and the limitations relative to fine texture of her donor hair. her primary goal was to be able to abandon her wig and to reestablish a frontal hairline in a more natural position. transplantation was done in april 2011, utilizing approximately 1200 grafts to the frontal hairline concentrated at the frontal tuft and mid-scalp. at 1-year post-transplant, with no medical intervention, the grafts demonstrated stable growth (figure 2a, b). the patient was re-evaluated yearly until 2014. at that time, she was satisfied with her hair restoration and had abandoned her wig (figure 3a, b). she did have a mild telogen effluvium in 2014 due to new-onset thyroid disease, but to date there has been no evidence of re-activation of her scarring alopecia. figure 1. pre-transplantation: regression of frontal hairline, atrophic porcelain quality of upper forehead skin (a), scant hair growth at crown and mid-scalp but no active disease (b). general “fine” hair texture and diffuse loss in uninvolved scalp. a b skin march 2018 volume 2 issue 2 copyright 2018 the national society for cutaneous medicine 142 figure 2. 1-year post-transplant. lowered, fuller frontal hairline (a) and improvement of hair growth at the crown and mid-scalp (b). figure 3. 3-year post-transplant. persistent improvement in frontal hairline (a) and at crown and mid-scalp (b) a b a b skin march 2018 volume 2 issue 2 copyright 2018 the national society for cutaneous medicine 143 lpp/ffa is a cicatricial alopecia and is especially problematic from the aspects of medical therapy and surgical restoration. most medical therapy is of limited success, with the main goal being to halt progression of hair loss. treatments include topical, intralesional, and oral corticosteroids; hydroxychloroquine; tetracyclines; 5αreductase inhibitors; pioglitazone; and immunosuppressants. 1 surgical restoration is known to cause re-activation of disease to the implanted follicles and their subsequent obliteration, but reports also suggest hair transplantation can cause primary activation of lpp in patients not previously known to have the disease. 2,3 it is the authors’ opinion that activation of lpp after hair transplantation is more likely undiagnosed lpp that pre-dated the hair transplant. one case report indicates hair transplantation in lpp patients can be successful if scalp and beard hair are combined and platelet rich plasma (prp) is injected intradermally prior to graft placement. 4 it is important to note that the follow-up period was only 10 months whereas other reports suggest graft rejection may not start until well over a year after transplantation. in addition, there was more than one variable in the procedure (scalp hair / beard hair / prp), so it is impossible to know if there were a true causative effect. here we present a case from a large hair restoration practice who has had durable remission of lpp/ffa after fut transplantation. we attribute the remission of the disease process to her incidental chemotherapy for breast cancer. we also raise the question to the medical community, especially our oncology colleagues: is there any potentially safe method by which chemotherapy drugs could be administered topically for this disfiguring cicatricial alopecia? conflict of interest disclosures: none. funding: none. corresponding author: allison l. limmer, bs, ba 6431 fannin st. houston, tx 77030 allison.l.limmer@uth.tmc.edu references: 1. whiting da. cicatricial alopecia: clinicpathological findings and treatment. clin dermatol. 2001;19:211-25. 2. jiménez f, poblet e. is hair transplantation indicated in frontal fibrosing alopecia? the results of test grafting in three patients. dermatol surg. 2013;39:1115-8. 3. donovan j. lichen planopilaris after hair transplantation: report of 17 cases. dermatol surg. 2012;38:1998-2004. 4. saxena k, saxena dk, savant ss. successful hair transplant outcome in cicatricial lichen planus of the scalp by combining scalp and beard hair along with platelet rich plasma. j cutan aesthet surg. 2016;9:51-5. discussion s1 why publish this special issue? a new paradigm in the use of technology to aid in the widespread dissemination of dermatologic knowledge we have all been there…putting in hours of work into a clinical research poster presented at a major academic conference, only to have the information within lost forever following the conclusion of the meeting. at skin: the journal of cutaneous medicinetm, we understand the importance of preserving and disseminating such vital information. research efforts aside, the loss of knowledge to the dermatology community that occurs each time a poster is discarded goes against the spirit of broad-based knowledge dissemination and academic pursuit. while publication expenses and space limitations have limited the ability to distribute scientific posters through traditional print venues, we at skin see the great potential in using an online platform to make free open access to poster presentations beyond those who attend a conference a possibility. in the interest of applying technology to education and to meet this challenge, we are proud to introduce our first supplemental issue. in this issue of skin, you will find 138 scientific posters presented at the 2017 fall clinical dermatology conference® in las vegas, nv, from october 12-15, 2017, grouped by topic. we hope that making this knowledge easily available to you will facilitate expedited dissemination into clinical practice where appropriate. the editors of skin hope that you will find the information presented to be informative and useful and look forward to your thoughts and ideas of how we can continue to make skin optimize its value to you. poster supplement section editors mark lebwohl md professor and chairman, dermatology, icahn school of medicine at mount sinai, new york james del rosso do adjunct clinical professor, touro university college of osteopathic medicine, henderson, nv darrell s rigel md, ms clinical professor of dermatology, new york university school of medicine, new york, ny synopsis patients with moderate to severe plaque psoriasis were treated with certolizumab pegol for up to 144 weeks, initially dosed at either 200 mg or 400 mg every two weeks. high proportions of patients achieved and maintained stringent absolute pasi thresholds. patients • patient inclusion and exclusion criteria have been reported previously.2 statistical analysis • proportions of patients achieving an absolute pasi score <5, <3, and <2 through weeks 0–144 (week 0 czp-randomized patients) or weeks 16–144 (placebo-randomized week 16 pasi 50 non-responders) are reported. • patients who were withdrawn at week 32 or later due to lack of pasi 50 response, and those randomized to czp who entered the escape arm at week 16, were treated as non-responders at subsequent timepoints. all other missing data were imputed using markov chain monte carlo (mcmc) multiple imputation methodology. responder rates reflect the simple average response; calculations included patients who did and did not dose adjust during the ole. results patient population and baseline characteristics • at week 0, 175 and 186 patients were randomized to czp 400 mg q2w and czp 200 mg q2w, respectively. • 72 placebo-randomized patients did not achieve pasi 50 at week 16 and entered the open-label czp 400 mg q2w escape arm. • baseline demographics are shown in table 1. achievement and maintenance of low absolute pasi thresholds • patients randomized to czp demonstrated an initial rapid response, maintained to week 48 (figure 2). – in czp 400 mg q2w-randomized patients, responder rates decreased during the ole following mandatory dose reduction (figure 2a). – in czp 200 mg q2w-randomized patients, improvements were sustained to week 144 (figure 2b). • 32 weeks after switching to open-label czp 400 mg q2w treatment (study week 48), 66.0% of patients initially randomized to placebo achieved pasi <2, and 75.9% achieved pasi <3 (figure 2c). responder rates were maintained through 128 weeks of czp treatment (study week 144). conclusions high proportions of patients dosed with both czp 400 mg q2w and czp 200 mg q2w achieved and maintained stringent absolute pasi thresholds. objectives to assess the long-term maintenance of absolute pasi <5, <3, and the more stringent <2 over three years in patients enrolled in two identically designed czp in pso phase 3 trials, the data from which were pooled. background • plaque psoriasis (pso) is an immune-mediated, inflammatory disease that affects around 2−4% of adults.1 • certolizumab pegol (czp) is an fc-free, pegylated anti-tumor necrosis factor (anti-tnf) with demonstrated efficacy and safety in the treatment of moderate to severe pso.2,3 • an absolute psoriasis area and severity index (pasi) score ≤5 has been associated with good quality of life in patients with pso,4 while a pasi score ≤3 is considered excellent.5,6 methods study design • data were pooled from two phase 3 trials in adults with pso: cimpasi-1 (nct02326298) and cimpasi-2 (nct02326272). • at week 0, patients were randomized 2:2:1 to receive czp 200 mg every 2 weeks (q2w) (400 mg loading dose at weeks 0, 2, and 4), czp 400 mg q2w, or placebo. • patients included in this analysis were either: – randomized to czp 200 mg q2w or czp 400 mg q2w at week 0, or; – randomized to placebo at week 0, did not achieve ≥50% improvement from baseline in pasi (pasi 50) at week 16, and entered the open-label escape arm where they received czp 400 mg q2w for up to 128 weeks (figure 1). • patients receiving double-blinded treatment who achieved pasi 50 at week 48 received czp 200 mg q2w upon entry to the open-label extension (ole). • dosing adjustment was permitted from week 48 onwards based on pasi response and the investigator’s discretion. a.b. gottlieb,1 a. blauvelt,2 d. thaçi,3 y. poulin,4 f. brock,5 c. arendt,6 m. boehnlein,7 k. reich8 figure 1 study design: cimpasi-1 and cimpasi-2 figure 2 achievement and maintenance of low absolute pasi thresholds through to week 144 author affiliations: 1department of dermatology, icahn school of medicine at mount sinai, new york, ny, usa; 2oregon medical research center, portland, or, usa; 3institute and comprehensive center for inflammation medicine, university of lübeck, lübeck, germany; 4centre de recherche dermatologique du québec métropolitain, québec, canada; 5ucb pharma, slough, uk; 6ucb pharma, brussels, belgium; 7ucb pharma, monheim am rhein, germany; 8translational research in inflammatory skin diseases, institute for health services research in dermatology and nursing, university medical center hamburg-eppendorf, and skinflammation® center, hamburg, germany. presented at fall clinical dermatology conference 2020 | october 29–november 1 | las vegas, nv reductions in absolute pasi over 144 weeks of treatment with certolizumab pegol in patients with plaque psoriasis: pooled analysis from two phase 3 trials (cimpasi-1 and cimpasi-2) references: 1parisi r. j invest dermatol 2013;133:377–85; 2gottlieb ab. jaad 2018;79:302–14; 3lebwohl m. jaad 2018;79:266–76; 4zweegers j. et al. br j dermatol 2017;176:786–93; 5carrascosa carrillo jm. j dermatolog treat 2017;29:140–4; 6puig l. eur j dermatol 2015;25:410–7. author contributions: substantial contributions to study conception/design, or acquisition/analysis/interpretation of data: abg, ab, dt, yp, fb, ca, mb, kr; drafting of the publication, or revising it critically for important intellectual content: abg, ab, dt, yp, fb, ca, mb, kr; final approval of the publication: abg, ab, dt, yp, fb, ca, mb, kr. author disclosures: abg: received honoraria as an advisory board member and consultant for avotres therapeutics, beiersdorf, boehringer ingelheim, bristol-myers squibb co., eli lilly, incyte, janssen, leo pharma, novartis, sun pharma, ucb pharma, and xbiotech (only stock options which she has not used); and has received research/educational grants from boehringer ingelheim, incyte, janssen, novartis, sun pharma, ucb pharma, and xbiotech; ab: served as a scientific adviser and/or clinical study investigator for abbvie, aclaris, allergan, almirall, athenex, boehringer ingelheim, bristol-myers squibb, dermavant, dermira inc., eli lilly, forte, galderma, janssen, leo pharma, novartis, ortho, pfizer, regeneron, sandoz, sanofi genzyme, sun pharma, and ucb pharma, and as a paid speaker for abbvie; dt: honoraria for participation on advisory boards, as a speaker and for consultancy from abbvie, almirall, amgen, biogen-idec, boehringer ingelheim, bristol myers squibb, celgene, ds-biopharma, eli lilly, galapagos, janssen, leo pharma, morphosis, novartis, pfizer, regeneron, samsung, sandoz-hexal, sanofi and ucb pharma; research grants received from celgene, leo pharma and novartis; yp: investigator (research grants) from abbvie, baxter, boehringer ingelheim, celgene, centocor/janssen, eli lilly, emd serono, gsk, leo pharma, medimmune, merck, novartis, pfizer, regeneron, takeda, and ucb pharma. speaker (honoraria) from abbvie, celgene, janssen, eli lilly, leo pharma, novartis, regeneron, and sanofi genzyme; fb, ca, mb: employees of ucb pharma; kr: served as advisor and/or paid speaker for and/or participated in clinical trials sponsored by abbvie, affibody, almirall, amgen, avillion, biogen, boehringer ingelheim, bristol myers squibb, celgene, centocor, covagen, dermira, eli lilly, forward pharma, fresenius medical care, galapagos, gsk, janssen, kyowa kirin, leo pharma, medac, msd, miltenyi biotec, novartis, ocean pharma, pfizer, regeneron, samsung bioepis, sanofi, sun pharma, takeda, ucb pharma, valeant/bausch health, and xenoport. acknowledgements: the studies were funded by dermira inc. in collaboration with ucb pharma. ucb is the regulatory sponsor of certolizumab pegol in psoriasis. we thank the patients and their caregivers in addition to the investigators and their teams who contributed to this study. the authors acknowledge susanne wiegratz, msc, ucb pharma, monheim am rhein, germany for publication coordination and dan smith, ba (hons), costello medical, cambridge, uk for medical writing and editorial assistance and the costello medical design team for design support. all costs associated with development of this poster were funded by ucb pharma in accordance with the good publication practice (gpp3) guidelines. bsa: body surface area; czp: certolizumab pegol; dlqi: dermatology life quality index; il: interleukin; ld: loading dose; mcmc: markov chain monte carlo; ole: open-label extension; pasi: psoriasis area and severity index; pasi 50/75: 50%/75% or greater improvement from baseline in pasi; pga: physician’s global assessment; psa: psoriatic arthritis; pso: plaque psoriasis; q2w: every two weeks; sd: standard deviation; tnf: tumor necrosis factor. week 0 14416 4832 initial treatment period (double-blinded) maintenance period (double-blinded) open-label treatment <pasi 50 (weeks 32–132) – withdrawn placebo q2w lda <pasi 50 open-label escape czp 400 mg q2w czp 200 mg q2w open-label dose switchingb 1:2:2 randomization lda ≥pasi 50, <pasi 75 czp 200 mg q2w czp 400 mg q2w aloading dose of czp 400 mg q2w at weeks 0, 2, and 4 or weeks 16, 18, and 20; bdepending on pasi response, any dose adjustments were either mandatory or at the investigator’s discretion. patients who did not achieve pasi 50 at week 32, 40, or 48 during double-blinded maintenance treatment, or at any visit after receiving unblinded czp 400 mg q2w for 12 weeks, were withdrawn from the study. 97/132 (73%) who entered the ole remained on czp 200 mg q2w 38/60 (63%) who entered the ole remained on czp 400 mg q2w r e sp o n d e r ra te ( % ) 90 week 0 84 966048403224168 72 108 120 132 144 czp 200 mg q2wb czp 200 mg q2w (open-label) week 0–48 week 48–144adose continuation pasi <5 pasi <3 pasi <2 80 70 60 50 40 30 20 10 0 100 r e sp o n d e r ra te ( % ) 90 week 0 84 966048403224168 72 108 120 132 144 czp 400 mg q2w (open-label) czp 400 mg q2w (open-label) week 16–48 week 48–144a pasi <5 pasi <3 pasi <2 80 70 60 50 40 30 20 10 0 100 dose continuation r e sp o n d e r ra te ( % ) 90 week 0 84 966048403224168 72 108 120 132 144 czp 400 mg q2w czp 200 mg q2w (open-label) week 0–48 week 48–144adose reduction pasi <5 pasi <3 pasi <2 80 70 60 50 40 30 20 10 0 100 p la c e b o 81/130 (62%) who entered the ole remained on czp 200 mg q2w 75.9% 58.2% 44.3% 74.9% 63.1% 53.3% 72.4% 59.9% 49.7% 79.0% 65.7% 53.6% 87.0% 75.9% 66.0% 80.7% 66.5% 57.2% 80.7% 62.0% 49.7% 82.2% 73.8% 63.6% 71.0% 59.6% 44.9% missing data were imputed using mcmc methodology and responder rates reflect the simple average response; calculations included patients who did and did not dose adjust during the ole. adosing adjustment was permitted during the open-label period based on pasi response, and was either mandatory or at the investigator’s discretion; bpatients received loading dose of czp 400 mg at weeks 0, 2, and 4. table 1 demographics and baseline characteristics of included patients apatients received loading dose of czp 400 mg at weeks 0, 2, and 4; bpresence of concomitant psa was self-reported. czp 400 mg q2w (n=175) czp 200 mg q2wa (n=186) placebo/escape czp 400 mg q2w (n=72) age (years), mean ± sd 45.0 ± 12.9 45.6 ± 13.2 46.7 ± 13.1 male, n (%) 103 (58.9) 125 (67.2) 48 (66.7) caucasian, n (%) 160 (91.4) 173 (93.0) 64 (88.9) weight (kg), mean ± sd 92.0 ± 24.8 95.1 ± 23.4 91.6 ± 21.6 duration of pso (years), mean ± sd 18.5 ± 12.6 17.7 ± 12.9 16.9 ± 11.9 concomitant psa,b n (%) 41 (23.4) 32 (17.2) 8 (11.1) pasi, mean ± sd 19.6 ± 7.3 19.2 ± 7.2 18.3 ± 6.3 bsa (%), mean ± sd 23.6 ± 14.3 23.5 ± 14.9 22.4 ± 13.8 pga score, n (%) 3: moderate 126 (72.0) 128 (68.8) 53 (73.6) 4: severe 49 (28.0) 58 (31.2) 19 (26.4) dlqi total score, mean ± sd 13.7 ± 6.9 14.3 ± 7.4 12.9 ± 7.4 any prior systemic therapy use for pso, n (%) 124 (70.9) 131 (70.4) 52 (72.2) prior biologic use, n (%) 59 (33.7) 62 (33.3) 23 (31.9) anti-tnf 40 (22.9) 44 (23.7) 14 (19.4) anti-il-17 8 (4.6) 16 (8.6) 4 (5.6) anti-il-12/il-23 10 (5.7) 3 (1.6) 6 (8.3) previously presented at aad 2020 a) czp 400 mg q2w-randomized patients (n=175) b) czp 200 mg q2w-randomized patients (n=186) c) placebo-randomized patients who entered the open-label czp 400 mg q2w escape arm at week 16 (n=72) skin july 2018 volume 2 issue 4 copyright 2018 the national society for cutaneous medicine 224 in-depth review current therapy for advanced melanoma and a look at future signaling pathways to target peter chow bs a , pablo angulo do b , kasie kudrewicz adkins do c a university of kansas school of medicine, wichita, ks b children’s specialty center of nevada, las vegas, nv c group health trihealth physician partners, cincinnati, oh melanoma is a deadly skin cancer arising from melanocytes, the cells in the basal layer of the epidermis responsible for forming the pigment in our skin, hair and eyes. melanoma’s incidence has continuously increased throughout the years. 1 due to public awareness and advancements in diagnostic methods, cases of melanoma frequently are diagnosed earlier through surgical excision, and thus carry a good prognosis and 5-year survival rate. 2 however, advanced metastatic stages of melanoma (iii and iv) have proven to be difficult to treat, with traditional chemotherapeutic drugs like dacarbazine (dtic) proving ineffective. in more recent years, targeted therapy, most famously, vemurafenib, a drug that targets melanomas harboring a v600e mutation, have shown improvement and promise in treating metastatic melanoma. 1 even still, metastatic melanoma has proven resilient to new treatments with its unique, heterogenous resistance mechanisms, requiring new approaches to bypass resistance. 3 abstract metastatic melanoma is a heterogeneous tumor of the skin derived from melanocytes notorious for its resistance to various forms of systemic therapy. many different types of monotherapies and combination therapies have been developed in recent years, each with their own setbacks, and drawbacks. this review article will provide an overview of current fda approved drug therapies for stage iii and iv metastatic melanoma, key signaling pathways they target, and mechanisms of drug resistance. this paper will then look at future therapy for metastatic melanoma with a particular focus on targeted therapy on embryonic and evolutionarily conserved pathways in metastatic melanoma, including notch, wnt, hippo, hedgehog signaling, among others. introduction skin july 2018 volume 2 issue 4 copyright 2018 the national society for cutaneous medicine 225 interferon alpha-2b traditional therapy for melanoma includes surgery, radiation and systemic therapy, the latter a category which encompasses chemotherapy and immunotherapy. 4 immunotherapy enhances the body’s immune function to combat tumors. fda approved management options for resected stage iii melanoma immunotherapy includes interferon alpha-2b. interferon alpha-2b has multiple actions in the body, including binding to cell receptors and subsequently initiating increased phagocytic activity of macrophages and increased cytotoxicity of lymphocytes. interferon alpha-2b has shown benefit in relapse-free survival benefit (1.72 vs 0.98 years), but no significant difference in overall survival (os). 5 interleukin-2 fda approved immunotherapy options for stage iv melanoma includes interleukin-2 (il-2). il-2 is a t-cell growth factor. treatment with il-2 carries only a 16% overall response rate with a 6% complete response. 6 anti-ctla-4 antibody more recent research has focused on activating adaptive and innate immune responses against tumor antigens. ipilimumab is an fda-approved immunotherapy for stage iv melanoma. 7 it is a monoclonal antibody that blocks cytotoxic t-lymphocyte-associated antigen 4 (ctla4), which normally acts as an immune checkpoint in the body that inhibits t cell activation. therefore, by targeting ctla-4, ipilimumab enhances t cell activation and cytokine production. in a phase 3 randomized controlled study, ipilimumab significantly improved overall survival in metastatic melanoma. 8 data suggested a 28% to 34% decrease in mortality rates in advanced melanoma patients who were treated with ipilimumab and a significant improvement in overall survival. 7 however, drawbacks can include a potential vast and dangerous array of autoimmune side effects, including but not limited to: enterocolitis, hypophysitis, pancreatitis, leukopenia, hepatitis, and these drug toxicities can be treatment-limiting and life threatening. 8,9 pd-1 and pd-l1 inhibitors programmed cell death protein 1 (pd-1) is a receptor expressed on lymphocytes that binds its ligand pd-l1 expressed on tumor cells. the pd-1/pd-l1 is an immune checkpoint interaction that ultimately leads to t cell exhaustion and tumor cell evasion. 10 nivolumab is a monoclonal antibody developed to target pd-1, inhibiting its interaction with pd-l1, and potentiating immune responses against tumor cells. 11 clinical trials have shown promising results of nivolumab compared to other therapies 11 , and the efficacy of nivolumab combined with ipilimumab in a phase 3 clinical trial has shown significant regression when the two immune checkpoint blockers were combined when compared to either drug alone. 4 chemotherapy dacarbazine (dtic) is the only fda approved chemotherapy drug for the treatment of advanced melanoma. dtic is believed to be an alkylating agent that adds methyl adducts onto dna, inducing cytotoxic and antitumor effects. 12 however, responses to it are low at 5-12%, the responses to the treatment themselves do not last long, and it has not been proven to prolong overall survival. 13,14 current fda approved immunotherapy and chemotherapy for stage iii and iv melanoma (table 1) skin july 2018 volume 2 issue 4 copyright 2018 the national society for cutaneous medicine 226 table 1. overview of currently available immunotherapy and chemotherapy options for advanced melanoma fda approved immunotherapy and chemotherapy for stage iii and iv melanoma drug mechanism of action common side effects interferon alpha2b increases macrophage phagocytosis, increases cytotoxicity of lymphocytes, and blocks oncogene expression flu-like symptoms, elevated transaminases, nausea, vomiting, diarrhea, neutropenia, leukopenia, thrombocytopenia interleukin-2 t cell growth factor flu-like symptoms, hypotension, arrhythmias, nausea, vomiting, diarrhea, oliguria ipilimumab blocks ctla-4 immune checkpoint inhibition, causing enhanced t cell activation and cytokine production. rash, nausea, diarrhea, fatigue, weight loss nivolumab blocks pd-1 and pd-l1 immune checkpoint interaction between tumor and t lymphocyte, ultimately preventing tumor cell evasion. fatigue, malaise, hyperglycemia, hypertriglyceridemia, hyponatremia, lymphocytopenia. skin july 2018 volume 2 issue 4 copyright 2018 the national society for cutaneous medicine 227 braf inhibitors the brafv600 somatic missense mutation is in approximately 66% of malignant melanomas. 15 the mutation entails a constitutively active ras-raf-mitogenactivated protein kinase (mapk) pathway, a pathway that is in charge of cell growth and proliferation. braf inhibitors that are fda approved for unresectable stage iii melanoma and stage iv melanoma harboring a brafv600 mutation include vemurafenib and dabrafenib. vemurafenib’s initial efficacy and low toxicity profile were documented in a 2011 phase 3 randomized clinical trial by chapman et al comparing vemurafenib to dtic in patients harboring a brafv600 mutation. in the study, the overall survival of patients receiving vemurafenib compared to dacarbazine was 84% at 6 months with a relative risk of death reduction of 63%. 16 another braf inhibitor, dabrafenib, was approved in 2013, and it showed similar results to vemurafenib. 17 due to mechanisms of resistance, the longevity of efficacy of a braf inhibitor has been called into question. the response duration to treatment ranges from 2 months to more than 18 months. 18 researchers have shown that melanoma has a diverse array of mechanisms of resistance to escape braf inhibitor drug therapy. in a study by shi et al examining acquired resistance to melanoma braf inhibitor therapy, multiple mechanisms of resistance were detected from tumor samples from patients: an estimated 52% of melanomas escaped via mapk reactivating mechanisms, 4% escaped via the phosphatidylinositol 3’-kinase (pi3k)-ptenakt pathway, 18% escaped via both core pathways, and 26% of melanomas escaped in an unknown fashion. additionally, when they were able to take samples from multiple tumors in the same patient, they discovered 81% (13/16) patients harbored multiple mechanisms of resistance. 19 mek + braf combination inhibitors in order to further improve survival rates in melanoma patients harboring a brafv600 mutation, combination therapy targeting other aspects of the ras-raf-mapk pathways have been believed to be a potential method to overcome escape pathways of melanoma cells to braf inhibitor monotherapy. trametinib is an fda approved targeted therapy option for patients who carry the brafv600e who have unresectable stage iii melanoma or stage iv melanoma. trametinib targets mek, a protein downstream of braf. a phase 3 clinical trial showed the benefits of combining a braf inhibitor (dabrafenib) with the mek inhibitor, trametinib. robert et al’s results show that combining dabrafenib with trametinib compared to vemurafenib alone yielded positive outcomes: overall survival rate at 12 months was 72% in combination treatment compared to 65% in vemurafenib alone. 20 there are still patients who fail combination therapy though, and when they do fail they form a more aggressive, metastatic melanoma. 21 additionally, in many cases of combined mek-braf inhibitor treatment, approximately 30% of patients still have signs of progressive disease at 6 months. 22 current fda approved targeted drug treatments for melanoma (table 2) skin july 2018 volume 2 issue 4 copyright 2018 the national society for cutaneous medicine 228 table 2. overview of currently available targeted therapy for advanced melanoma fda approved targeted therapy for stage iii and iv melanoma drug mechanism of action common side effects vemurafenib targets brafv600 mutation in mapk pathway fatigue, prolonged q-t interval, hypertension, peripheral neuropathy, rash, alopecia, skin photosensitivity, arthralgia, keratoacanthoma, dabrafenib targets brafv600 mutation in mapk pathway hyperglycemia, skin rash, fatigue, headache, lymphocytopenia, arthralgia trametinib targets mek in patients with a brafv600 mutation, a protein downstream to braf in the mapk pathway rash, hypoalbuminemia, diarrhea, anemia, elevated transaminases table 3. important melanoma signaling pathways signaling pathways that are potential targets for future melanoma therapies pathway involvement in melanoma kit a receptor that can be targeted upstream of the mapk pathway pi3k/akt a pathway involved in tumor angiogenesis and invasion. notch embryonic cell pathway that possibly promotes tumor chemoresistance, tumorigenesis and progression wnt related to melanoma tumor formation and metastasis hippo a pathway thought to contribute to melanoma invasion and metastasis. hedgehog involved in spatiotemporal development in embryos as well as melanoma cell proliferation and metastasis. skin july 2018 volume 2 issue 4 copyright 2018 the national society for cutaneous medicine 229 kit inhibitors kit is a transmembrane receptor tyrosine kinase upstream of the ras-braf-mapk pathway, and is in charge of cell survival and proliferation in melanocytes. 23 many melanomas on mucosal, acral, and sun damaged sites harbor kit mutations. 24 thus, kit inhibitors like imatinib can be a possible drug therapy. guo et al’s phase 2 trial of imatinib on kit mutations in metastatic melanoma showed that imatinib demonstrated significant activity against patients with a kit mutation. 25 however, they do note imatinib’s overall response rate (23.3%) is much lower than that of vemurafenib, which had an 81% response rate in braf patients, indicating the kit inhibitor has a lower specificity. in another study of imatinib treatment of metastatic melanoma, challenges in identifying appropriate patients for kit inhibition treatment was highlighted. compared to braf mutations, kit mutations can be more widely distributed in the coding region, providing patient identification challenges in kit inhibitor therapy. 24 thus, although kit inhibitors have had meaningful treatment outcomes in melanoma, more research is required to enhance responsiveness to this targeted therapy’s overall response rate. pi3k/akt pathway the pi3k (phosphatidylinositol 3 kinase)akt-mtor pathway is involved in cell proliferation, invasion, metabolism, and angiogenesis in normal and tumor cells. 26 it is separate from the ras-raf-mapk pathway. there are studies now elucidating the relationship between the mapk and pi3k pathways and mechanisms of tumor resistance to targeted drug therapy. in patient cell lines who were resistant to a raf or mek inhibitor, the pi3k pathway was found to be frequently upregulated or persistent in response. 26 thus, co-targeting the pi3k and braf pathways can potentially enhance metastatic melanoma sensitivity and prevent drug resistance. so far, co-targeting of mek and pi3k/mtor pathways showed more effective inhibition of braf mutant melanoma cell lines compared to the braf and pi3k/mtor cotargeting inhibition. 27 more testing and in a wider number and range of patients is required to further elucidate the relationship. another protein involved in the pi3k pathway is phosphatase and tensin homolog deleted in from chromosome 10 (pten), a tumor suppressor gene. pten is a pi3k pathway inhibitor, and its loss has been associated with tumor development in 3050% of melanomas. 28,29 in stahl et al’s study of mice models, pten loss was associated with decreased apoptosis in melanoma cells and pten expression associated with increased apoptosis. 30 furthermore, there have been studies that show that braf mutant melanoma cells actually utilize pten loss in order to progress to metastatic melanoma. the combination of braf mutation and loss of pten is estimated in approximately 20% of melanomas. 31 thus, a more intricate understanding of pten expression, pi3k pathway, mapk and their role in melanoma tumorigenesis will be useful for combating resistance. notch pathway the notch pathway is a new avenue in battling melanoma which holds promise in preventing chemoresistance. the notch pathway is an evolutionarily conserved embryonic cell pathway important for cell fate and differentiation. 32 studies have suggested that dysregulated notch signaling can prolong and confer life to cancer stem cells, which are thought to be important in tumor chemoresistance. 33 other studies the promising future of melanoma therapy (table 3) skin july 2018 volume 2 issue 4 copyright 2018 the national society for cutaneous medicine 230 have shown that notch activation promotes melanoma tumorigenesis and progression. 32 thus, therapeutic benefit of targeting notch signaling includes preventing tumor angiogenesis, cancer stem cell depletion, and cell death. 34 the notch receptor family consists of four transmembrane receptors (notch 1-4). 35 recent research on melanoma cells correlate metastasis of melanoma cells with expression of notch4 gene, suggesting this protein and the notch pathway can be a potential target of melanoma therapy. 36 there is currently research on drug therapy that can target notch signaling in melanoma cells. kaushik et al have demonstrated that honokiol (a biphenolic organic compound) can target notch signaling, confirmed with decreased downstream effector target genes of notch: hes-1, and cyclin d1. 35 wnt signaling pathway the wnt signaling pathway is important for cell proliferation, differentiation, migration, and many other processes of cell fate during embryonic development. 37 beta-catenin is a downstream transcription factor of the wnt pathway that can translocate to the nucleus for target gene expression. understanding of the wnt signaling pathway in melanoma progression may be critical-studies have found canonical and noncanonical wnt signaling effect different stages of tumor progression, with canonical affecting melanoma formation and noncanonical affecting melanoma metastasis. 38 there exists controversy in regards to the exact involvement wnt signaling has on melanoma behavior. one study showed loss of nuclear beta-catenin staining was associated with aggressive melanoma behavior, 39 and another study showed that elevated levels of nuclear beta-catenin was associated with reduced proliferation of melanoma cells. 40 combined these findings suggest that wnt/beta-catenin signaling is important for melanoma cell homeostasis, and if dysregulated, can lead to transformation of melanoma cells. 41 hippo signaling while many drug therapies and studies are focusing on the ras-raf-mapk pathway in melanoma, fewer studies are focusing on targeting the invasive potential of melanoma cells. the mechanisms underlying melanoma invasion are presently poorly understood. the hippo pathway (the salvador-warts-hippo) is an evolutionarily conserved mechanism in charge of tissue and cell growth. 42 downstream in the hippo pathway are yap and taz effector proteins which are amplified in many cancers and promote epithelial-mesenchymal transition-a frequent hallmark of metastasis. 43 in a model of skin reconstruct, yap overexpression led to increased melanoma cell invasiveness, and yap knockdown led to decreased metastasis potential. 43 thus, mutations in the hippo pathway yield increased activation of yap and taz, which promote metastasis regardless of braf mutation status in melanomas. 42,44 current research is examining verteprofin, 44 a molecule that inhibits yap function and whether or not it can successfully regulate hippo effector functions and subsequently melanoma invasion. hedgehog pathway another way to target cancer stem cells involves the hedgehog signaling pathway. this is an evolutionarily conserved pathway in charge of spatiotemporal development in embryos. 45 the pathway includes smoothened g-protein coupled receptor-like receptor (smo) 45 and downstream of smo include many transcription factors including gli1 and gli2, both proven in recent years to help melanoma cell proliferation and metastasis. 46,47 microarray gene expression profiles of metastatic melanoma tumors skin july 2018 volume 2 issue 4 copyright 2018 the national society for cutaneous medicine 231 showed elevated smo, which correlated with overall decreased survival in melanoma patients. 45 promising studies have demonstrated that by selectively blocking smo in the hedgehog pathway with nvplde-225, melanoma growth is suppressed in vitro and in vivo. 45,48 melanoma is a heterogenous tumor capable of resisting drugs through escape mechanisms. existing fda approved monotherapies have mostly been unsuccessful in the treatment of metastatic melanoma. emerging research targeting embryonically conserved pathways, among others, are showing promising solutions to beating this cancer. conflict of interest disclosures: none funding: none corresponding author: peter chow, bs university of kansas, school of medicine 1010 n kansas street, wichita, ks pchow@kumc.edu references: 1. tang t, eldabaje r, yang l. current status of biological therapies for the treatment of metastatic melanoma. anticancer res. 2016 jul;36(7):3229-41. review. 2. paluncic j, kovacevic z, jansson pj, kalinowski d, merlot am, huang ml, lok hc, sahni s, lane dj, richardson dr. roads to melanoma: key pathways and emerging players in melanoma progression and oncogenic signaling. biochim biophys acta. 2016 apr;1863(4):770-84. 3. shi h, hugo w, kong x, hong a, koya rc, moriceau g, chodon t, guo r, johnson db, dahlman kb, kelley mc, kefford rf, chmielowski b, glaspy ja, sosman ja, van baren n, long gv, ribas a, lo rs. acquired resistance and clonal evolution in melanoma during braf inhibitor therapy. cancer discov. 2014 jan;4(1):80-93. 4. wolchok jd, chiarion-sileni v, gonzalez r, rutkowski p, grob jj, cowey cl, lao cd, wagstaff j, schadendorf d, ferrucci pf, smylie m, dummer r, hill a, hogg d, haanen j, carlino ms, bechter o, maio m, marquezrodas i, guidoboni m, mcarthur g, lebbé c, ascierto pa, long gv, cebon j, sosman j, postow ma, callahan mk, walker d, rollin l, bhore r, hodi fs, larkin j. overall survival with combined nivolumab and ipilimumab in advanced melanoma. n engl j med. 2017 oct 5;377(14):1345-1356. 5. fox mc, lao cd, schwartz jl, frohm ml, bichakjian ck, johnson tm. management options for metastatic melanoma in the era of novel therapies: a primer for the practicing dermatologist: part i: management of stage iii disease. j am acad dermatol. 2013 jan;68(1):1.e1-9; quiz 10-12. 6. fox mc, lao cd, schwartz jl, frohm ml, bichakjian ck, johnson tm. management options for metastatic melanoma in the era of novel therapies: a primer for the practicing dermatologist: part ii: management of stage iv disease. j am acad dermatol. 2013 jan;68(1):13.e1-13; quiz 26-8. 7. o'sullivan coyne g, madan ra, gulley jl. nivolumab: promising survival signal coupled with limited toxicity raises expectations. j clin oncol. 2014 apr 1;32(10):986-8. conclusion skin july 2018 volume 2 issue 4 copyright 2018 the national society for cutaneous medicine 232 8. hodi fs, o'day sj, mcdermott df, weber rw, sosman ja, haanen jb, gonzalez r, robert c, schadendorf d, hassel jc, akerley w, van den eertwegh aj, lutzky j, lorigan p, vaubel jm, linette gp, hogg d, ottensmeier ch, lebbé c, peschel c, quirt i, clark ji, et al. improved survival with ipilimumab in patients with metastatic melanoma. n engl j med. 2010 aug 19;363(8):711-23. 9. weber j. ipilimumab: controversies in its development, utility and autoimmune adverse events. cancer immunol immunother. 2009 may;58(5):823-30. 10. dolan de, gupta s. pd-1 pathway inhibitors: changing the landscape of cancer immunotherapy. cancer control. 2014 jul;21(3):231-7. 11. johnson db, peng c, sosman ja. nivolumab in melanoma: latest evidence and clinical potential. ther adv med oncol. 2015 mar;7(2):97-106. 12. marchesi f, turriziani m, tortorelli g, avvisati g, torino f, de vecchis l. triazene compounds: mechanism of action and related dna repair systems. pharmacol res. 2007 oct;56(4):275-87. 13. garbe c, eigentler tk, keilholz u, hauschild a, kirkwood jm. systematic review of medical treatment in melanoma: current status and future prospects. oncologist. 2011;16(1):5-24. 14. atkinson v. medical management of malignant melanoma. aust prescr. 2015 jun;38(3):74-8. 15. davies h, bignell gr, cox c, stephens p, edkins s, clegg s, teague j, woffendin h, garnett mj, bottomley w, davis n, dicks e, ewing r, floyd y, gray k, hall s, hawes r, hughes j, kosmidou v, menzies a, mould c, parker a, et al. mutations of the braf gene in human cancer. nature. 2002 jun 27;417(6892):949-54. 16. chapman pb, hauschild a, robert c, haanen jb, ascierto p, larkin j, dummer r, garbe c, testori a, maio m, hogg d, lorigan p, lebbe c, jouary t, schadendorf d, ribas a, o'day sj, sosman ja, kirkwood jm, eggermont am, dreno b, nolop k, et al. improved survival with vemurafenib in melanoma with braf v600e mutation. n engl j med. 2011 jun 30;364(26):2507-16. 17. hauschild a, grob jj, demidov lv, jouary t, gutzmer r, millward m, rutkowski p, blank cu, miller wh jr, kaempgen e, martínalgarra s, karaszewska b, mauch c, chiarion-sileni v, martin am, swann s, haney p, mirakhur b, guckert me, goodman v, chapman pb. dabrafenib in braf-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial. lancet. 2012 jul 28;380(9839):358-65. 18. flaherty kt, puzanov i, kim kb, ribas a, mcarthur ga, sosman ja, o'dwyer pj, lee rj, grippo jf, nolop k, chapman pb. inhibition of mutated, activated braf in metastatic melanoma. n engl j med. 2010 aug 26;363(9):809-19. 19. shi h, hugo w, kong x, hong a, koya rc, moriceau g, chodon t, guo r, johnson db, dahlman kb, kelley mc, kefford rf, chmielowski b, glaspy ja, sosman ja, van barenn, long gv, ribas a, lo rs. acquired resistance and clonal evolution in melanoma during braf inhibitor therapy. cancer discov. 2014 jan;4(1):80-93. skin july 2018 volume 2 issue 4 copyright 2018 the national society for cutaneous medicine 233 20. robert c, karaszewska b, schachter j, rutkowski p, mackiewicz a, stroiakovski d, lichinitser m, dummer r, grange f, mortier l, chiarion-sileni v, drucis k, krajsova i, hauschild a, lorigan p, wolter p, long gv, flaherty k, nathan p, ribas a, martin am, sun p, et al. improved overall survival in melanoma with combined dabrafenib and trametinib. n engl j med. 2015 jan 1;372(1):30-9. 21. smalley ks, fedorenko iv. inhibition of braf and braf+mek drives a metastatic switch in melanoma. mol cell oncol. 2015 mar 19;2(4):e1008291. 22. long gv, stroyakovskiy d, gogas h, levchenko e, de braud f, larkin j, garbe c, jouary t, hauschild a, grob jj, chiarion sileni v, lebbe c, mandalà m, millward m, arance a, bondarenko i, haanen jb, hansson j, utikal j, ferraresi v, kovalenko n, mohr p, et al. combined braf and mek inhibition versus braf inhibition alone in melanoma. n engl j med. 2014 nov 13;371(20):1877-88. 23. wehrle-haller b. the role of kit-ligand in melanocyte development and epidermal homeostasis. pigment cell res. 2003 jun;16(3):287-96. 24. carvajal rd, antonescu cr, wolchok jd, chapman pb, roman ra, teitcher j, panageas ks, busam kj, chmielowski b, lutzky j, pavlick ac, fusco a, cane l, takebe n, vemula s, bouvier n, bastian bc, schwartz gk. kit as a therapeutic target in metastatic melanoma. jama. 2011 jun 8;305(22):2327-34. 25. guo j, si l, kong y, flaherty kt, xu x, zhu y, corless cl, li l, li h, sheng x, cui c, chi z, li s, han m, mao l, lin x, du n, zhang x, li j, wang b, qin s. phase ii, open-label, single-arm trial of imatinib mesylate in patients with metastatic melanoma harboring c-kit mutation or amplification. j clin oncol. 2011 jul 20;29(21):2904-9. 26. atefi m, von euw e, attar n, ng c, chu c, guo d, nazarian r, chmielowski b, glaspy ja, comin-anduix b, mischel ps, lo rs, ribas a. reversing melanoma cross-resistance to braf and mek inhibitors by co-targeting the akt/mtor pathway. plos one. 2011;6(12):e28973. 27. penna i, molla a, grazia g, cleris l, nicolini g, perrone f, picciani b, del vecchio m, de braud f, mortarini r, anichini a. primary cross-resistance to brafv600e-, mek1/2and pi3k/mtorspecific inhibitors in braf-mutant melanoma cells counteracted by dual pathway blockade. oncotarget. 2016 jan 26;7(4):3947-65. 28. paluncic j, kovacevic z, jansson pj, kalinowski d, merlot am, huang ml, lok hc, sahni s, lane dj, richardson dr. roads to melanoma: key pathways and emerging players in melanoma progression and oncogenic signaling. biochim biophys acta. 2016 apr;1863(4):770-84. 29. wu h, goel v, haluska fg. pten signaling pathways in melanoma. oncogene. 2003 may 19;22(20):3113-22. 30. stahl jm, cheung m, sharma a, trivedi nr, shanmugam s, robertson gp. loss of pten promotes tumor development in malignant melanoma. cancer res. 2003 jun 1;63(11):2881-90. 31. dankort d, curley dp, cartlidge ra, nelson b, karnezis an, damsky we jr, you mj, depinho ra, mcmahon m, bosenberg m. braf(v600e) cooperates with pten loss to skin july 2018 volume 2 issue 4 copyright 2018 the national society for cutaneous medicine 234 induce metastatic melanoma. nat genet. 2009 may;41(5):544-52. 32. pinnix cc, herlyn m. the many faces of notch signaling in skin-derived cells. pigment cell res. 2007 dec;20(6):458-65. 33. capaccione km, pine sr. the notch signaling pathway as a mediator of tumor survival. carcinogenesis. 2013 jul;34(7):142030. 34. koch u, radtke f. notch signaling in solid tumors. curr top dev biol. 2010;92:411-55. 35. kaushik g, venugopal a, ramamoorthy p, standing d, subramaniam d, umar s, jensen ra, anant s, mammen jm. honokiol inhibits melanoma stem cells by targeting notch signaling. mol carcinog. 2015 dec;54(12):1710-21. 36. lin x, sun b, zhu d, zhao x, sun r, zhang y, zhang d, dong x, gu q, li y, liu f. notch4+ cancer stem-like cells promote the metastatic and invasive ability of melanoma. cancer sci. 2016 aug;107(8):107991. 37. komiya y, habas r. wnt signal transduction pathways. organogenesis. 2008 apr;4(2):68-75. 38. kulikova, ksenia & kibardin, alexey & gnuchev, n.v. & georgiev, g.p. & larin, sergey. (2012). wnt signaling pathway and its significance for melanoma development. sovremennye tehnologii v medicine. 2012. 107-111. 39. bachmann im, straume o, puntervoll he, kalvenes mb, akslen la. importance of p-cadherin, beta-catenin, and wnt5a/frizzled for progression of melanocytic tumors and prognosis in cutaneous melanoma. clin cancer res. 2005 dec 15;11(24 pt1):8606-14. 40. chien aj, moore ec, lonsdorf as, kulikauskas rm, rothberg bg, berger aj, major mb, hwang st, rimm dl, moon rt. activated wnt/beta-catenin signaling in melanoma is associated with decreased proliferation in patient tumors and a murine melanoma model. proc natl acad sci u s a. 2009 jan 27;106(4):1193-8. 41. kovacs d, migliano e, muscardin l, silipo v, catricalà c, picardo m, bellei b. the role of wnt/β-catenin signaling pathway in melanoma epithelial-to-mesenchymal-like switching: evidences from patients-derived cell lines. oncotarget. 2016 jul 12;7(28):4329543314. 42. harvey kf, zhang x, thomas dm. the hippo pathway and human cancer. nat rev cancer. 2013 apr;13(4):246-57. 43. nallet-staub f, marsaud v, li l, gilbert c, dodier s, bataille v, sudol m, herlyn m, mauviel a. pro-invasive activity of the hippo pathway effectors yap and taz in cutaneous melanoma. j invest dermatol. 2014 jan;134(1):123-132. 44. sanchez im, aplin ae. hippo: hungry, hungry for melanoma invasion. j invest dermatol. 2014 jan;134(1):14-16. 45. o'reilly ke, de miera ev, segura mf, friedman e, poliseno l, han sw, zhong j, zavadil j, pavlick a, hernando e, osman i. hedgehog pathway blockade inhibits melanoma cell growth in vitro and in vivo. pharmaceuticals (basel). 2013 nov 11;6(11):1429-50. skin july 2018 volume 2 issue 4 copyright 2018 the national society for cutaneous medicine 235 46. stecca b, mas c, clement v, zbinden m, correa r, piguet v, beermann f, ruiz i altaba a. melanomas require hedgehog-gli signaling regulated by interactions between gli1 and the ras-mek/akt pathways. proc natl acad sci u s a. 2007 apr 3;104(14):5895-900. 47. alexaki vi, javelaud d, van kempen lc, mohammad ks, dennler s, luciani f, hoek ks, juàrez p, goydos js, fournier pj, sibon c, bertolotto c, verrecchia f, saule s, delmas v, ballotti r, larue l, saiag p, guise ta, mauviel a. gli2-mediated melanoma invasion and metastasis. j natl cancer inst. 2010 aug 4;102(15):1148-59. 48. jalili a, mertz kd, romanov j, wagner c, kalthoff f, stuetz a, pathria g, gschaider m, stingl g, wagner sn. nvplde225, a potent and selective smoothened antagonist reduces melanoma growth in vitro and in vivo. plos one. 2013 jul 30;8(7):e69064. skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 336 brief articles treatment of pityriasis rubra pilaris with adalimumab: a case report joshua r. kaminetsky baa,b, eric j. feit baa,b, jonathan p. ungar mda adepartment of dermatology, icahn school of medicine at mount sinai, new york, ny balbert einstein college of medicine, bronx, ny a 65-year-old woman with a history of hypertension, hypercholesterolemia, and successfully excised melanoma presented with an “itchy rash”. the rash had begun several months earlier and had now progressed to involve most of the body. the patient endorsed moderate pruritus. physical exam revealed generalized erythematous and scaly plaques with follicular keratosis of the trunk, abdomen, extremities, face, and scalp. marked scaling and fissuring of the feet and hands were noted. the groin and antecubital fossae were spared. topical emollients had yielded no improvement. she was also treated with ultraviolet phototherapy without success. biopsy samples taken from the back and temple demonstrated chronic spongiotic and psoriasiform dermatitis. the epidermis was acanthotic with foci of mild intercellular edema, scattered parakeratotic foci, and perivascular mononuclear infiltrate. flow cytometry with peripheral smear was negative, excluding possible cutaneous t cell lymphoma. the histologic findings, combined with the clinical picture, favored a diagnosis of pitryriasis rubra pilaris. the patient was started on adalimumab 40 mg every two weeks and noted marked improvement of erythema, scale, and pruritus at her first follow-up visit. she continued on adalimumab, and her lesions had completely resolved by her last visit save for a few remaining areas of mild follicular hyperkeratosis. abstract pityriasis rubra pilaris (prp) is a rare inflammatory dermatosis of unknown etiology and variable presentation. common clinical features include hyperkeratotic follicular papules, palmoplantar hyperkeratosis and well-demarcated red-orange scaly plaques interspersed with islands of unaffected skin. a limited body of anecdotal evidence predominantly supports the use of systemic retinoids and/or methotrexate in treating the disease. in a subset of these patients, there has been a documented role for biologic tumor necrosis factor (tnf) inhibitors, especially in patients who have failed retinoid or antimetabolite therapy. we present a case of a woman whose prp responded favorably to adalimumab, highlighting the role of tnf inhibitors and the need for their continued exploration in the treatment of prp. case report skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 337 figure 1. notable erythema and scaling of the dorsum of the hand prior to treatment. figure 2. marked resolution of disease following adalimumab. like other rare diseases, prp’s low incidence—as low as 1 in 400,000 according to some estimates—poses a challenge in the development of effective and widely accepted treatment recommendations, as large controlled trials are difficult to conduct. augmenting this low incidence, the poorly understood etiology and pathophysiology of the disease has resulted in treatment algorithms based largely on anecdotal evidence such as case series and case reports. in light of this, we hope reporting of our case will contribute to the ever-growing body of literature supporting adalimumab and other tnf inhibiting agents in the treatment of prp. while mild cases of prp can be responsive to topical agents, extensive disease like our patient’s necessitates systemic therapy. based on the current literature, the most utilized treatment is systemic retinoid therapy1, most commonly isotretinoin 1-1.5 mg/kg/day. for those patients who are not candidates for retinoids, 10-25 mg of methotrexate weekly has demonstrated efficacy as well.2 though potentially effective, both systemic retinoids and methotrexate are associated with notable adverse effects, ranging from mild xerosis to teratogenicity, hepatotoxicity, and myelosuppression. given the limitations of the above mentioned first line therapies for prp, other classes of medication are often necessary. though the pathogenesis of prp is not fully understood, immunologic and inflammatory factors likely contribute on a cellular and biomolecular level. tnf-alpha is a proinflammatory cytokine known to play a role in many inflammatory disorders such as psoriasis, crohn’s disease, ulcerative colitis, and rheumatoid arthritis. similarly, it has been demonstrated that tnf-alpha levels are upregulated in areas of skin affected by prp.3 it follows, therefore, that tnf inhibitors could produce a beneficial effect in treating the disease. indeed, over the last ten years there have been a growing number of reports of tnf inhibitors demonstrating success in treating refractory patients or those intolerant of retinoids or antimetabolites. agents that have met success include etanercept4, infliximab5, and—as in our case— adalimumab6,7,8,910, with some patients showing complete resolution. adalimumab is a recombinant human monoclonal antibody with high affinity for tnf-alpha, thereby combating some of the inflammatory discussion skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 338 processes underlying the disease. systemic review of the role of anti-tnf agents in prp has demonstrated marked clinical response within three to eight weeks in those patients who received adalimumab monotherapy.11 while potentially beneficial for patients, tnf inhibitors are not without risks of their own. adverse effects include injection site reactions, headaches, and increased creatine kinase. downregulation of immune surveillance is also an undesired concomitant effect of tnf inhibitors’ anti-inflammatory properties. this leaves patients more susceptible to a variety of infections, as well as some malignancies. weighing these effects is of particular importance in our patient’s case given her history of melanoma, as there are accumulating reports that antitnf agents may be associated with the development or recurrence of latent malignancies, specifically malignant melanoma.12 our case adds to the continually expanding body of evidence advocating anti-tnf agents in the treatment of prp. while their therapeutic effects must certainly be weighed against their risks, these medications are often well tolerated by patients, and clinicians should continue to consider and further explore their use for appropriate candidates. conflict of interest disclosures: dr. ungar is an employee of the mount sinai medical center, which receives research funds from abgenomics, amgen, anacor, boehringer ingleheim, celgene, ferndale, lilly, janssen biotech, kadmon, leo pharmaceuticals, medimmune, novartis, pfizer, sun pharmaceuticals, and valeant pharmaceuticals. funding: none. corresponding author: joshua kaminetsky 1425 madison avenue, 15th floor new york, ny 10029 jkaminet@mail.einstein.yu.edu references: 1) borok m, lowe nj. pityriasis rubra pilaris. further observations of systemic retinoid therapy. j am acad dermatol. 1990;22(5 pt 1):792. 2) chapalain v, beylot-barry m, doutre ms, beylot c. treatment of pityriasis rubra pilaris: a retrospective study of 14 patients. j dermatolog treat. 1999;10:113-117. 3) zhang yh, zhou y, ball n, su mw, xu jh, zheng zz. type i pityriasis rubra pilaris: upregulation of tumor necrosis factor alpha and response to adalimumab therapy. j cutan med surg. 2010 jul;14(4):185-8. 4) seckin d, tula e, ergun t. successful use of etanercept in type i pityriasis rubra pilaris. br j dermatol 2008; 158: 642-4. 
 5) garcovich s, di giampetruzzi ar, antonelli g, garcovich a, didona b. treatment of refractory adult-onset pityriasis rubra pilaris with tnf-alpha antagonists: a case series. j eur acad dermatol venereol. 2010;24(8):881. 6) walling hw, swick bl. pityriasis rubra pilaris responding rapidly to adalimumab. arch dermatol. 2009 jan;145(1):99-101.1 7) o'kane d, devereux ce, walsh my, hoey se. rapid and sustained remission of pityriasis rubra pilaris with adalimumab treatment. clin exp dermatol. 2010;35(4):e155. 8) schreml s, zeller v, babilas p, karrer s, landthaler m, szeimies rm. pityriasis rubra pilaris successfully treated with adalimumab. clin exp dermatol. 2010 oct;35(7):792-3. 9) wassef c, lombardi a, rao bk. adalimumab for the treatment of pityriasis rubra pilaris: a skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 339 case reprot. cutis. 2012 november;90(5):244247. 10) bravo e, carrion l, paucar, sm, mendoza r, rivera c. successful treatment of pityriasis rubra pilaris with adalimumab. dermatol online journal. 2014 jan;20(4):11. 11) petrof g, almaani n, archer c, griffiths w, smith c. a systematic review of the literature on the treatment of pityriasis rubra pilaris type 1 with tnf-antagonists. jeadv 2013; 27: 1315. 
 12) kouklakis g, efremidou e, pitiakoudis m, et al. development of primary malignant melanoma during treatment with a tnf-α antagonist for severe crohn’s disease: a case report and review of the hypothetical association between tnf-α blockers and cancer. drug des devel ther. 2013.7: 195-9 powerpoint presentation ` mcscc (n=10) locally advanced cscc (n=16) overall (n=26) median age, years (min–max) 71 (56–86) 73 (56–88) 73 (56–88) males, n (%) 8 (80.0) 13 (81.3) 21 (80.8) ecog performance status, n (%) 0 4 (40.0) 6 (37.5) 10 (38.5) 1 6 (60.0) 10 (62.5) 16 (61.5) primary cscc site, n (%) head/neck 5 (50.0) 13 (81.3) 18 (69.2) extremity 3 (30.0) 2 (12.5) 5 (19.2) trunk 1 (10.0) 1 (6.3) 2 (7.7) genital 1 (10.0) 0 1 (3.8) any prior systemic therapy, n (%) 9 (90.0) 6 (37.5) 15 (57.7) any prior radiation therapy, n (%) 6 (60.0) 14 (87.5) 20 (76.9) number of doses of cemiplimab, median, (min–max) 12.5 (3–23) 10.0 (2–24) 11.0 (2–24) months of follow up, median, (min–max) 7.3 (1.6–13.8) 6.6 (1.1–13.3) 6.9 (1.1–13.8) presented at the 13th winter clinical dermatology conference, january 12–17, 2018, lahaina, hi, usa (encore of asco 2017 oral presentation) cemiplimab (regn2810), a fully human anti-pd-1 monoclonal antibody, for patients with unresectable locally advanced or metastatic cutaneous squamous cell carcinoma (cscc): initial safety and efficacy from expansion cohorts of phase 1 study kyriakos p. papadopoulos,1 taofeek k. owonikoko,2 melissa l. johnson,3 irene braňa,4 marta gil-martin,5 raymond p. perez,6 victor moreno,7 april k. salama,8 emiliano calvo,9 nelson s. yee,10 howard safran,11 antonio gonzález-martín,12 raid aljumaily,13 daruka mahadevan,14 kosalai k. mohan,15 jingjin li,16 elizabeth stankevich,15 israel lowy,15 matthew g. fury,15 jade homsi17 1south texas accelerated research therapeutics, san antonio, tx, usa; 2emory winship cancer institute, atlanta, ga, usa; 3sarah cannon research institute, nashville, tn, usa; 4vall d’hebron institute of oncology, barcelona, spain; 5institut català d'oncologia, barcelona, spain; 6unversity of kansas, fairway, ks, usa; 7start madrid fundacion jimenez diaz, madrid, spain; 8duke university medical center, durham, nc, usa; 9start madrid, hospital madrid norte sanchinarro, madrid, spain; 10penn state cancer institute, hershey, pa, usa; 11miriam hospital, providence, ri, usa; 12formerly of md anderson international españa, madrid, spain; 13university of oklahoma health sciences center, oklahoma city, ok, usa; 14formerly of university of arizona cancer center, tucson, az, usa; 15regeneron pharmaceuticals inc., tarrytown, ny, usa; 16regeneron pharmaceuticals inc., basking ridge, nj; 17formerly of banner md anderson cancer, gilbert, az, usa. • selected inclusion criteria include: – eastern cooperative oncology group (ecog) performance status of 0 or 1. – measureable disease by recist 1.1. – adequate organ function (bone marrow, kidney, liver). – mcscc (m1): expansion cohort 7. – unresectable locally and/or regionally advanced cscc (m0): expansion cohort 8: • acceptable reasons for surgery to be deemed inappropriate are: – recurrence of cscc after 2 or more surgical procedures and an expectation that curative resection would be unlikely, and/or; – substantial morbidity or deformity anticipated from surgery. • selected exclusion criteria: – autoimmune disease within 5 years. – active brain metastases. – other invasive malignancy within 5 years (no exclusion for tumors considered cured by localized treatment). – immunosuppressive doses of steroids (>10 mg prednisone daily or equivalent). – systemic antitumor treatment within 4 weeks of initial dose of cemiplimab. – history of solid organ transplant. – tumors of lip or eyelid not eligible for cscc cohorts. results patient characteristics • as of april 27, 2017 (data cut-off date), 26 patients (median age, 73 years) from the cscc expansions cohorts have been treated with cemiplimab. • patient characteristics and exposure to cemiplimab are summarized in table 1. disclosures dr. kyriakos papadopoulos: institutional research funding from abbvie, medimmune, daiichi sankyo, glaxosmithkline, regeneron, sanofi, armo biosciences, arqule, amgen, calithera biosciences, curagenix, incyte, merck, peloton therapeutics, 3d medicines, formation biologics, emd serona. taofeek owonikoko: consulting/advisory role for abbvie, celgene, eisai, g1 therapeutics, genentech/roche, eli lilly, novartis, sandoz, and takeda; institutional research funding from abbvie, astellas pharma, astrazeneca/medimunne, bayer, bms, celgene, g1 therapeutics, novartis, regeneron, stemcentrix; institutional patents, royalties, other intellectual property from “overcoming acquired resistance to chemotherapy treatments through suppression of stat3; selective chemotherapy treatments and diagnostics methods related thereto”. melissa johnson: institutional consulting/advisory role for astellas, bi, celgene, genentech/roche, otsuka; research funding from array, biopharm, astrazeneca, bergenbio, checkpoint therapeutics, inc., emd serono, genentech/roche, genemab, janseen, kadmox, lilly, mirati therapeutics, inc., novartis, oncomed, pfizer, regeneron, stementrx. irene braňa: no disclosures. marta gil martin: no disclosures. raymond perez: consulting/advisory role for pharmaceutical research associates; institutional research funding from agensys, altor bioscience, bristol-myers squibb, dompe farmaceutici, genentech/roche, immunogen, incyte, lilly, medimmune, millennium, novartis, onyx, regeneron, tetralogic pharmaceuticals. victor moreno: no disclosures. april salama: honoraria and consulting/advisory role for bms; institutional research funding from abbvie, bms, celldex, genentech, gsk, immunocore, merck, reata pharmaceuticals. emiliano calvo: consulting/ advisory role for astellas pharma, gsk, lilly/imclone, nanobiotix, novartis, pfizer, roche/genentech; speakers bureau fee from novartis; institutional research funding from abbvie, boehringer ingelheim, bristol-myers, squibb, eisai, janssen oncology, lilly, merck, millenium, nektar, novartis, oncomed, pfizer, pharmamar, psi oxus, puma biotechnology, roche/genentech, sanofi, spectrum pharmaceuticals. nelson yee: consulting/ advisory role for bayer; institutional research funding from emd serono, medpace, momenta pharmaceuticals, onxeo, pharmacycles, regeneron. howard safran: no disclosures. antonio gonzález-martín: consulting/advisory role for, speakers bureau and travel/accommodations/expenses fees from roche and pharmamar, speakers bureau and travel/accommodations/expenses fees from astrazeneca. raid aljumaily: no disclosures. daruka mahadevan: no disclosures. kosalai mohan: stockholder and employee of regeneron pharmaceuticals, inc. jingjin li: stockholder and employee of regeneron pharmaceuticals, inc. elizabeth stankevich: employee of regeneron pharmaceuticals, inc., stockholder at regeneron pharmaceuticals, inc., bms, celgene, merck. israel lowy: stockholder and employee of regeneron pharmaceuticals, inc. matthew fury: stockholder and employee of regeneron pharmaceuticals, inc.; consulting/advisory role for egenix; research funding from astrazeneca/medimmune, novartis, regeneron; institutional patents, royalties, other intellectual property from regeneron. jade homsi: honoraria and speakers’ bureau fees from genentech, merck; consulting/advisory role for castle biosciences, novartis; research funding from bristol-myers squibb, regeneron; travel/accommodations/expenses from genentech, merck, novartis. references 1. papadopoulos kp et al. j clin oncol. 2016:34 (suppl; abstr 3024). 2. karia ps et al. j am acad dermatol. 2013;68:957–966. 3. stratigos a et al. eur j cancer. 2015;51:1989–2007. 4. karia ps et al. j clin oncol. 2014;32:327–334. 5. cranmer ld et al. oncologist. 2010;15:1320–1328. ` table 1. patient characteristics and exposure to cemiplimab †5 patients not evaluated by immunohistochemistry: 1 cr, 1 pr, 2 sd, 1 pd; ‡includes 1 unconfirmed pr. ne, not evaluable. figure 4. early response to cemiplimab in a 62-year old male with locally advanced cscc screening response after 6 weeks of cemiplimab ` figure 5. durable response with cemiplimab in an 86-year old with cscc of trunk, metastatic to bilateral axillary lymph nodes screening >6 months after treatment discontinuation background • cemiplimab (regn2810) is a human immunoglobulin g4 monoclonal antibody directed against pd-1.1 • phase 1 results from the first 60 patients with advanced solid tumors showed no dose-limiting toxicities:1 – the most common treatment-related adverse events were fatigue (28%), arthralgia (12%), and nausea (12%). – the overall response rate was 18%. • cemiplimab 3 mg/kg every 2 weeks (q2w) was selected for further study in expansion cohorts. • as of april 27, 2017, 392 patients have been enrolled in the phase 1 study. • cutaneous squamous cell carcinoma (cscc) is the 2nd most common skin cancer in us.2 • risk factors for cscc include ultraviolet exposure, advanced age, immunosuppression.3 – there is a predominance of males and a median age of 71 years at diagnosis.4 • cscc has a surgical cure rate of >95% in early stage disease; however, a small percentage of patients develop unresectable locally advanced or metastatic cscc4 – us mortality: 3,900–8,800/year.4 • there is no widely accepted standard of care systemic therapy for locally advanced or metastatic cscc (mcscc).5 – conventional cytotoxic chemotherapy can induce tumor responses, but often is poorly tolerated among older patients with cscc. – in a single arm trial with cetuximab (n=36), median overall survival was 8.1 months.6 • in phase 1 dose escalation study of cemiplimab, a durable radiologic complete response to cemiplimab was achieved in a cscc patient.1,7 • there is a higher mutation burden in cscc than any tumor type in the cancer genome atlas (tcga).8 • immunosuppression is a well-described risk factor for cscc (especially in solid organ transplant patients).9 • programmed death-ligand 1 (pd-l1) expression has been associated with high-risk disease10; cscc tumors may therefore be responsive to pd-1 checkpoint blockade. objectives • the co-primary objectives of the cscc expansion cohorts of this phase 1 open label study were to: – characterize the safety and tolerability of intravenous cemiplimab 3 mg/kg. – evaluate the efficacy of cemiplimab by measuring overall response rate (orr). methods study design: cscc expansion cohorts (nct02383212) • cohort 7 enrolled 10 patients with mcscc and cohort 8 enrolled 16 patients with unresectable locally and/or regionally advanced cscc (figure 1). figure 1. study design: cscc expansion cohorts metastatic cscc cohort 7 (n=10) cemiplimab 3 mg/kg q2w, for up to 48 weeks response assessments every 8 weeks (recist 1.1)locally and/or regionally advanced cscc cohort 8 (n=16) research tumor biopsies were taken at screening and day 29±3. recist, response evaluation criteria in solid tumors. • all patients received cemiplimab 3 mg/kg q2w for up to 48 weeks (if no progression or intolerance), followed by post-treatment follow-up. – there is an option for re-treatment for patients who experienced disease progression during posttreatment follow-up, but no cscc patients have required this re-treatment option at this time. • all patients underwent tumor imaging every 8 weeks, and response assessments are per recist 1.1. • research biopsies were performed at baseline and at day 29. treatment-related teaes of any grade occurring in ≥2 patients, or ≥grade 3 in any patient number of patients (%) any grade ≥grade 3 fatigue 6 (23.1) 0 arthralgia 2 (7.7) 1 (3.8) rash, maculopapular 2 (7.7) 1 (3.8) diarrhea 2 (7.7) 0 nausea 2 (7.7) 0 hypothyroidism 2 (7.7) 0 asthenia 1 (3.8) 1 (3.8) aspartate aminotransferase elevation 1 (3.8) 1 (3.8) alanine aminotransferase elevation 1 (3.8) 1 (3.8) ` table 2. summary of treatment-related teaes (n=26) immunohistochemistry • a total of 17 of 21 evaluated tumors (81%) were positive (≥1%) for tumor expression of pd-l1 by immunohistochemistry (table 4). • there was no apparent association between pd-l1 immunohistochemistry results and objective responses. ` table 4. tumor pd-l1 expression by immunohistochemistry using dako 22c3 clone tumor pd-l1 total cr pr sd pd ne orr† number of patients ≥50% 8 0 3‡ 3 2 0 38% (3/8)‡ ≥1–49% 9 1 4 0 2 2 56% (5/9) <1% 4 0 2 1 1 0 50% (2/4) conclusions • this is the first prospective study of a pd-1 inhibitor in patients with advanced cscc. • cemiplimab was generally well tolerated in cscc in this predominantly older population. • both locally advanced and mcscc are highly responsive to cemiplimab (combined orr 46.2%), and durability is emerging. • eighty-one percent of pre-treatment tumor samples were pd-l1 positive. • a unifying characteristic of cutaneous malignancies appears to be responsiveness to immune checkpoint inhibition. • a phase 2 study is ongoing in patients with unresectable locally advanced and mcscc (nct02760498). 6. maubec e et al. j clin oncol. 2011;29:3419–3426. 7. falchook gs et al. j immunother cancer. 2016;4:70. 8. pickering cr et al. clin cancer res. 2014;20:6582–6592. 9. euvrard e et al. n engl j med. 2003;348:1681–1691. 10. slater na, googe pb. j cutan pathol. 2016;43:663–670. acknowledgments we thank the patients and their families, the investigators and study teams involved in this study. this study was funded by regeneron pharmaceuticals inc, and sanofi. we would like to acknowledge the following people from the study sponsors: bo gao, frank seebach, laura simpson, ana kostic, usman chaudhry, wilson caldwell, minjie feng, dale lesueur. medical writing support and typesetting was provided by prime, knutsford, uk, funded by sanofi and regeneron pharmaceuticals inc. treatment-emergent adverse events (teaes) • treatment-related teaes occurring in ≥2 patients overall, or ≥grade 3 in any patient are summarized in table 2. investigator assessment mcscc (n=10), n (%) locally advanced cscc (n=16), n (%) overall (n=26), n (%) complete response 0 2 (12.5) 2 (7.7) partial response 6 (60.0)† 4 (25.0) 10 (38.5) stable disease 1 (10.0) 5 (31.3) 6 (23.1) progressive disease 2 (20.0) 4 (25.0) 6 (23.1) not evaluated 1 (10.0) 1 (6.3) 2 (7.7) tumor response • tumor response by cohort are summarized in table 3. • investigator assessed preliminary orr (complete response [cr] + partial response [pr] + one unconfirmed pr) by recist 1.1 was 46.2% (12/26 patients; 95% ci: 26.6–66.6; intention-to-treat population). • disease control rate (dcr = orr + stable disease [sd]) was 69.2% (18/26 patients; 95% ci: 48.2–85.7). • clinical activity in all patients with at least 1 response evaluation of target lesions are shown in figure 2. • cemiplimab also produced rapid, deep and durable tumor reductions in target lesions in both cohorts (figure 3). ` table 3. best overall tumor response rate by cohorts †includes 5 confirmed partial responses and 1 unconfirmed partial response. ` figure 3. change in target lesion over time mcscc (recist responses) *patient progressed at subsequent assessment; however, the sum of target lesions are not evaluable. pd, progressive disease; upr, unconfirmed partial response. 1 2 3 4 5 6 7 8 9 11 40 20 0 –20 –40 –60 –80 –100 0 p er ce nt c ha ng e in ta rg et le si on s fr om b as el in e first cr/pr first pd months 10 12 * locally advanced (recist responses) locally advanced (sd, pd) • figure 4 shows a case example of a cscc patient with early response. • figure 5 shows a case example of a patient with cscc of trunk, metastatic to bilateral axillary lymph nodes, with durable response to cemiplimab. – cemiplimab was discontinued due to an adverse event (rash) after 3 doses; patient continued to maintain response >6 months after discontinuation. ` plot shows 22 patients who had at least 1 response evaluation. not listed are 4 enrolled patients who did not have at least 1 response evaluation due to death in cycle 1 (2 patients), early clinical progression but no scans (1 patient), and end-of-cycle 1 response assessment that showed new lesions but unevaluable target lesions (1 patient). †patient had new lesions at end of cycle 1. ‡patients had stable disease despite large decreases in target lesions: 1 patient discontinued treatment after cycle 1 due to arthralgia, so is stable disease by recist; 1 patient developed new lesions during cycle 2 so is stable disease by recist. b es t p er ce nt c ha ng e in ta rg et le si on s fr om b as el in e figure 2. clinical activity in all patients with at least 1 response evaluation of target lesions number of patients with confirmed responses = 11 one had progressive disease at 21 weeks, 10 remain in response (>8 to >40 weeks duration of responses) 40 20 0 –20 –40 –60 –80 –100 ‡‡† • two patients discontinued study treatment after treatment-related teaes – 86-year old female developed grade 3 rash after 3 doses; she continues post-treatment follow-up – 88-year old male withdrew consent following grade 3 transaminase elevation and grade 2 fatigue after 6 doses. • there were 2 deaths within 30 days of last dose of study drug, both considered unrelated to study drug. mcscc (sd, pd, upr) progressive disease stable disease unconfirmed response confirmed response slide number 1 skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 34 covid concepts new cases of syphilis and molluscum contagiosum in the covid19 pandemic: a sign that social distancing guidelines are not being adhered to? haley d. heibel, md1, parneet dhaliwal, do2, clay j. cockerell, md, mba1,3 1cockerell dermatopathology, dallas, tx 2department of pathology, baylor university medical center, dallas, tx 3departments of dermatology and pathology, ut southwestern medical center, dallas, tx to the editor: social distancing has played an important role in reducing the transmission of covid-19. however, in the covid-19 era, we have diagnosed multiple cases of syphilis and molluscum contagiosum histopathologically, the vast majority of which were not suspected by referring clinicians. as syphilis is spread by direct sexual contact and molluscum contagiosum by close physical contact (including sexual contact),1 if the general public had been uniformly adhering to social distancing and hand hygiene recommendations from the centers for disease control and prevention (cdc),2 we would theoretically expect no new diagnoses of these diseases. however, the number of syphilis (8) and molluscum contagiosum (88) cases were greater between the dates of march 1 to august 28, 2020, compared with number of cases of syphilis (5) and molluscum contagiosum (87) diagnosed between march 1 to august 28, 2019. the incidence of both of these diagnoses increased as the volume of specimens had decreased in 2020 (83,227) from 2019 (107,435) during this time period. abstract social distancing has played an important role in reducing the transmission of covid-19, and, if the general public uniformly followed social distancing guidelines, we would theoretically expect no new diagnoses of sexually transmitted diseases (stds) during this time period. however, during the covid-19 era, we have diagnosed multiple cases of syphilis and molluscum contagiosum histopathologically with an increased incidence in our practice from the dates of march 1 to august 28, 2020, compared with these dates in 2019. the vast majority of these cases were not suspected by referring clinicians. dermatologists are experts in the recognition of the cutaneous manifestations of venereal diseases which is critical to appropriate diagnosis and management, and they should continue to provide care during this pandemic. individuals who acquire stds during this time may increase the strain on already limited health care resources by disregarding social distancing recommendations. all medical providers must consider how we can better encourage individuals to abide by social distancing recommendations, optimize care for patients during the pandemic, and prevent the misallocation of valued health care resources. skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 35 this evidence suggests that, despite the consistent message regarding social distancing provided by the cdc, health care providers, and others, a proportion of the population is not abiding by these recommendations as well as engaging in unsafe risky sexual behavior. as primary syphilis occurs about 3 weeks after infection, and secondary syphilis occurs approximately 2 to 10 weeks after the primary chancre, some of these cases of syphilis may have been contracted prior to implementation of social distancing guidelines although this is unlikely.3 we theorize that quarantine and social distancing restrictions as well as stress from the pandemic itself and consequences of it (such as losing one’s job) may have led to a sensation of isolation, which influenced individuals to seek out human interaction in an ill-advised manner, including unsafe sexual practices. according to karen surita, acting sexually transmitted disease program (std) manager for the texas department of state health services (oral communication, september 2020), resources for contract tracing for stds in the texas department of state health services have been deployed to cases of covid-19 during the pandemic. therefore, these cases may not be traced as they normally would be. contact tracing for syphilis and other reportable diseases continues to be important to ensure appropriate treatment and evaluation of sexual contacts and to prevent spread of these diseases. covid-19 is bringing to the forefront the difficulties std public health programs have experienced for years. individuals who acquire stds during this time may increase the strain on already limited health care resources by disregarding social distancing recommendations. limited access to care and resources, especially in rural communities, has been a difficulty faced by public health programs in texas. therefore, education of the community, including patients, health care providers, and others, regarding testing guidelines for individuals who may be at risk for stds, as well as treatment and reporting of these conditions has been priority the texas department of state health services. this is becoming increasingly important with more limited staff and clinic availability in the context of covid-19 and social distancing guidelines. as many dermatology practices reduced inoffice patient visits during the pandemic, it is possible that venereal diseases with cutaneous manifestations were not evaluated by dermatologists, misdiagnosed or unrecognized, and that the incidence of these conditions is likely higher than we observed in our practice. dermatologists are experts in the recognition of the cutaneous manifestations of stds, which is critical to appropriate diagnosis and management, and they should continue to provide care during this pandemic. if patients sought care elsewhere and were misdiagnosed, this could have led to a delay in treatment for both patients and their partners as well as complications from progression of the disease process. dermatologists may play an integral role in the prevention, early recognition, and treatment of stds through routinely discussing safe sex practices with patients, appropriately screening patients who are suspected to be at risk for an std by obtaining a complete sexual history and testing them, and remaining up to date on the guidelines for the recommendations of testing and treatments for stds. all medical providers must consider how we can better encourage individuals to practice social skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 36 distancing not only to prevent the spread of covid-19 but also to prevent misallocation of valued health care resources. abbreviations used: centers for disease control and prevention (cdc), sexually transmitted disease (std) conflict of interest disclosures: none funding: none corresponding author: haley d. heibel, md 2110 research row suite 100 dallas, tx 75235 phone: 214-530-5200 email: hheibel@dermpath.com references: 1. murray, pr, rosenthal, ks, pfaller ma. medical microbiology. 7th ed. philadelpha, pa: saunders elsevier; 2013. 2. social distancing keep a safe distance and slow the spread. centers for disease control and prevention web site. https://www.cdc.gov/coronavirus/2019ncov/prevent-getting-sick/social-distancing.html. updated july 15, 2020. accessed july 24, 2020. 3. mcadam, aj, milner, da, sharpe ah. infectious diseases. in: kumar, v, abbas ak, aster jc, eds. robbins and contran pathologic basis of disease. 9th ed. philadelpha, pa: saunders elsevier; 2015: 341-402. mailto:hheibel@dermpath.com https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/social-distancing.html https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/social-distancing.html tapinarof cream 1% qd for the treatment of plaque psoriasis: efficacy and safety in two pivotal phase 3 trials mark lebwohl,1 linda stein gold,2 bruce strober,3 april armstrong,4 h chih-ho hong,5 leon kircik,1,6 jennifer soung,7 jeff fromowitz,8 scott guenthner,9 stephen c piscitelli,10 david s rubenstein,10 philip m brown,10 anna m tallman,10 robert bissonnette11 1icahn school of medicine, mount sinai, new york, ny, usa; 2henry ford health system, detroit, mi, usa; 3yale university, new haven and central connecticut dermatology research, cromwell, ct, usa; 4keck school of medicine university of southern california, los angeles, ca, usa; 5university of british columbia and probity medical research, surrey, bc, canada; 6skin sciences, pllc, louisville, ky, usa; 7southern california dermatology, santa ana, ca, usa; 8dermatology of boca, boca raton, fl, usa; 9the indiana clinical trials center, pc, plainfield, in, usa; 10dermavant sciences, inc., durham, nc, usa; 11innovaderm research inc., montreal, qc, canada synopsis ■ psoriasis is a chronic, immune-mediated disease characterized by scaly, erythematous, and pruritic plaques that can be painful and disfiguring1 ■ there is a need for efficacious topical therapies for plaque psoriasis without concerns for duration of treatment due to potential for long-term adverse effects or local intolerance. however, no topicals with novel mechanisms have been fda approved in recent years ■ tapinarof is a first-in-class, non-steroidal, topical therapeutic aryl hydrocarbon receptor modulating agent (tama) in development for the treatment of psoriasis and atopic dermatitis ■ psoaring 1 (nct03956355) and psoaring 2 (nct03983980) were two pivotal phase 3 studies designed to assess the efficacy and safety of tapinarof cream 1% once daily (qd) in patients with plaque psoriasis objective ■ to present the pivotal phase 3 primary efficacy endpoint (proportion of patients who achieved a physician global assessment [pga] response at week 12), key secondary efficacy endpoint (proportion of patients who achieved ≥75% improvement in psoriasis area and severity index [pasi75] from baseline at week 12), and safety results of psoaring 1 and 2 methods study design ■ in two identical, phase 3, multicenter (us and canada), double-blind, vehicle-controlled, randomized studies, patients with mild to severe plaque psoriasis were randomized 2:1 to receive tapinarof cream 1% qd or vehicle qd for 12 weeks (figure 1) ■ following the double-blind period, patients could enroll in a separate open-label, long-term extension study for an additional 40 weeks of treatment, or complete a follow-up visit 4 weeks after the end of treatment (week 16) figure 1. study design double-blind treatment (12 weeks) adult subjects with stable plaque psoriasis ■ aged 18–75 years ■ pga score ≥2* ■ bsa ≥3%–≤20% 2:1 2:1 n=510 n=515 tapinarof 1% qd (n=340) tapinarof 1% qd (n=343) vehicle qd (n=172) vehicle qd (n=170) r r *pga of 2 (mild) or 4 (severe) was limited to ~10% each of the total randomized population; ~80% of the randomized population had a pga of 3 (moderate). bsa, body surface area; pga, physician global assessment; qd, once daily; r, randomized endpoints and statistical analysis ■ the primary endpoint was pga response at week 12, defined as the proportion of patients with a pga score of clear (0) or almost clear (1) and ≥2-grade improvement in pga score from baseline to week 12 ■ the key secondary efficacy endpoint was the proportion of patients who achieved pasi75 from baseline to week 12 ■ the incidence, frequency, and nature of adverse events (aes) and serious aes were monitored from the start of study treatment until the end-of-study visit ■ efficacy endpoints were derived from the intent-to-treat (itt) population using multiple imputation analysis ■ p values for differences between tapinarof cream 1% qd and vehicle in both studies were calculated using cochran-mantel-haenszel analysis and stratified by baseline pga score results patient disposition and baseline characteristics ■ in psoaring 1 and 2, a total of 510 and 515 patients were randomized (itt), respectively, across 97 sites in the us and canada ■ overall, mean demographic and baseline characteristics were comparable across treatment groups and studies (table 1) ■ at baseline, 79.2% and 83.9% of patients had a pga score of 3, mean (standard deviation [sd]) pasi score was 8.9 (4.1) and 9.1 (3.8), and mean (sd) body surface area was 7.9% (4.8) and 7.6% (4.3) in psoaring 1 and 2, respectively table 1. baseline patient demographics and characteristics psoaring 1 psoaring 2 tapinarof 1% qd (n=340) vehicle qd (n=170) tapinarof 1% qd (n=343) vehicle qd (n=172) mean age, years (sd) 49.8 (13.7) 49.1 (13.3) 50.0 (13.1) 50.0 (13.7) male, n (%) 213 (62.6) 86 (50.6) 188 (54.8) 102 (59.3) weight, kg, mean (sd) 91.7 (24.6) 92.8 (22.7) 92.9 (24.3) 89.6 (19.9) bmi, kg/m2, mean (sd) 31.4 (7.8) 32.5 (7.6) 31.8 (7.7) 30.7 (6.3) pga, n (%) 2 – mild 39 (11.5) 21 (12.4) 28 (8.2) 15 (8.7) 3 – moderate 271 (79.7) 133 (78.2) 288 (84.0) 144 (83.7) 4 – severe 30 (8.8) 16 (9.4) 27 (7.9) 13 (7.6) pasi, mean (sd) 8.7 (4.0) 9.2 (4.4) 9.1 (3.7) 9.3 (4.0) bsa affected, %, mean (sd) 7.8 (4.6) 8.2 (5.1) 7.8 (4.4) 7.3 (4.1) itt population. bmi, body mass index; bsa, body surface area; itt, intent-to-treat; pasi, psoriasis area and severity index; pga, physician global assessment, qd, once daily; sd, standard deviation. primary endpoint: pga response ■ the primary endpoint (pga of 0 or 1 and ≥2-grade improvement at week 12) was met; pga response rates were highly statistically significant in the tapinarof cream 1% qd group versus the vehicle group in both psoaring 1 and 2: 35.4% vs 6.0% (p<0.0001) and 40.2% vs 6.3% (p<0.0001), respectively (figure 2) ■ figure 3 displays photographs of the clinical response of a patient treated with tapinarof 1% qd who achieved the primary and secondary efficacy endpoints at week 12 figure 2. pga response at week 12 itt population. p value based upon cochran-mantel-haenszel analysis stratified by baseline pga score. itt, intent-to-treat; pga, physician global assessment; qd, once daily; sem, standard error of mean. figure 3. clinical response of patient with plaque psoriasis treated with tapinarof 1% qd baseline week 4 week 12 pga and pasi are global efficacy assessments. example of one representative target lesion of one tapinarof 1% qd treated patient; individual results may vary. photographs demonstrate improvement in pga and pasi at week 4 and 12. pasi, psoriasis area and severity index; pga, physician global assessment; qd, once daily. secondary endpoint: pasi75 ■ pasi75 response rates at week 12 were highly statistically significant in the tapinarof cream 1% qd group versus the vehicle group in both psoaring 1 and 2: 36.1% vs 10.2% (p<0.0001) and 47.6% vs 6.9% (p<0.0001), respectively (figure 4) figure 4. pasi75 response at week 12 δ 25.9% 36.1% 10.2% p<0.0001 m e a n p a s i7 5 r e sp o n se ra te , % ( s e m ) psoaring 1 30 40 50 60 20 10 0 tapinarof 1% qd (n=340) vehicle qd (n=170) δ 40.7% 47.6% 6.9% p<0.0001 psoaring 2 tapinarof 1% qd (n=343) vehicle qd (n=172) itt population. p value based upon cochran-mantel-haenszel analysis stratified by baseline pga score. itt, intent-to-treat; pasi75, ≥75% improvement in psoriasis area and severity index; pga, physician global assessment; qd, once daily; sem, standard error of mean safety ■ overall, treatment-emergent aes (teaes) in psoaring 1 and 2 were comparable, in which the majority were mild or moderate in severity and most did not lead to study discontinuation (table 2) ■ the most common (≥1% in any group) treatment-related teaes were folliculitis, contact dermatitis, headache, pruritus, and dermatitis – folliculitis was mostly mild or moderate in severity in both studies, and study discontinuation due to folliculitis was low in psoaring 1 and 2: 1.8% (6/340) vs 0.0% (0/170) and 0.9% (3/343) vs 0.0% (0/172), respectively table 2. safety overview patients, n (%) psoaring 1 psoaring 2 tapinarof 1% qd (n=340) vehicle qd (n=170) tapinarof 1% qd (n=343) vehicle qd (n=172) teae 171 (50.3) 38 (22.4) 187 (54.5) 45 (26.2) mild 76 (22.4) 16 (9.4) 80 (23.3) 17 (9.9) moderate 82 (24.1) 22 (12.9) 98 (28.6) 28 (16.3) severe 11 (3.2) 0 (0.0) 8 (2.3) 0 (0.0) serious teae 9 (2.6) 0 (0.0) 7 (2.0) 0 (0.0) study discontinuation due to aes 19 (5.6) 0 (0.0) 20 (5.8) 1 (0.6) most common treatment-related teaes (≥1% in any group) folliculitis 70 (20.6) 2 (1.2) 54 (15.7) 1 (0.6) contact dermatitis 13 (3.8) 1 (0.6) 16 (4.7) 0 (0.0) headache 5 (1.5) 1 (0.6) 1 (0.3) 0 (0.0) pruritus 4 (1.2) 0 (0.0) 2 (0.6) 0 (0.0) dermatitis 1 (0.3) 0 (0.0) 4 (1.2) 0 (0.0) study discontinuation due to aesi folliculitis 6 (1.8) 0 (0.0) 3 (0.9) 0 (0.0) contact dermatitis 5 (1.5) 0 (0.0) 7 (2.0) 0 (0.0) headache 1 (0.3) 0 (0.0) 2 (0.6) 0 (0.0) severity of folliculitis, n (%) among subset of patients with aesi of folliculitis mild 51 (63.8) 1 (50.0) 44 (72.1) 0 (0.0) moderate 28 (35.0) 1 (50.0) 17 (27.9) 1 (100.0) severe 1 (1.3) 0 (0.0) 0 (0.0) 0 (0.0) a patient is counted once only for each meddra preferred term. safety population. teae defined as an ae that starts on or after the date of first dose of study drug. ae, adverse event; aesi, adverse event of special interest; meddra, medical dictionary for regulatory activities; qd, once daily; teae, treatment-emergent adverse event. conclusions ■ both the primary and secondary endpoints were met, demonstrating highly statistically significant and clinically meaningful efficacy with tapinarof cream 1% qd compared with vehicle ■ tapinarof cream 1% qd was well tolerated, consistent with previous studies2,3 ■ tapinarof cream 1% qd has potential to be the first topical psoriasis treatment with a novel mechanism of action in over 20 years references 1. menter a, et al. j am acad dermatol. 2008;58:826–850; 2. robbins k, et al. j am acad dermatol. 2019;80:714–721; 3. stein gold l, et al. j am acad dermatol. 2020; doi: 10.1016/j.jaad.2020.04.181. acknowledgments this study was funded by dermavant sciences, inc. the authors thank the participating investigators, patients and their families, and colleagues involved in the conduct of the study. editorial and medical writing support under the guidance of the authors was provided by apothecom, uk, and was funded by dermavant sciences, inc. in accordance with good publication practice (gpp3) guidelines (ann intern med. 2015;163:461–464). contact dr mark lebwohl at lebwohl@aol.com with questions or comments. δ 29.4% 35.4% 6.0% p<0.0001 m e a n t re a tm e n t su cc e ss , % ( s e m ) psoaring 1 30 40 50 60 20 10 0 tapinarof 1% qd (n=340) vehicle qd (n=170) δ 33.9% 40.2% 6.3% p<0.0001 psoaring 2 tapinarof 1% qd (n=343) vehicle qd (n=172) • pga = 3 • pasi = 17.6 • pga = 2 • pasi = 4 • pga = 0 • pasi = 0 poster presented at 13th annual winter clinical dermatology conference | maui, hi | january 12 17, 2018 patient-reported outcomes from two randomized, double-blind, vehicle-controlled phase 3 trials in axillary hyperhidrosis (atmos-1 & atmos-2) david m. pariser,1 adelaide a. hebert,2 janice drew,3 john quiring4, dee anna glaser5 1eastern virginia medical school and virginia clinical research, inc., norfolk, va; 2uthealth mcgovern medical school at houston, houston, tx; 3dermira, inc., menlo park, ca; 4qst consultations, allendale, mi; 5saint louis university, st. louis, mo introduction • hyperhidrosis affects an estimated 4.8% of the us population, or approximately 15.3 million people, and negative psychological consequences are experienced by approximately 75% of patients with the disorder1 • the prevalence of anxiety and depression is over 3.5 times greater in people with hyperhidrosis than in those without it, and there is a positive correlation between the severity of hyperhidrosis and rates of anxiety and depression2 • glycopyrronium tosylate (gt; formerly drm04) is a topical cholinergic receptor antagonist being developed for the treatment of primary axillary hyperhidrosis in patients ≥9 years of age • gt has been assessed in two randomized, phase 3 clinical trials (atmos-1 and atmos-2); the primary efficacy and safety results of these studies have been previously reported3 • patient-reported outcomes (pros) in these trials were assessed using recently developed axillary hyperhidrosis patient measures (ahpm) which includes three separate assessments: the 4-item axillary sweating daily diary (asdd; patients <16 years of age completed a modified, child-specific 2-item version [asdd-c]), 6 weekly impact items, and a single-item patient global impression of change (pgic)3,4 – asdd/asdd-c axillary sweating severity item (item 2) has been specifically developed and validated to support regulatory approval3 objective • to evaluate changes in patient-reported outcomes after 4 weeks of treatment with gt compared with vehicle in atmos-1 and atmos-2 methods atmos-1 and atmos-2 study design • atmos-1 (drm04-hh04; nct02530281) and atmos-2 (drm04-hh05; nct02530294) were parallel-group, 4-week, double-blind, phase 3 clinical trials in which patients with primary axillary hyperhidrosis were randomized (2:1) to gt or vehicle (figure 1) – coprimary endpoints included asdd axillary sweating severity item (item 2) responder rate (defined as ≥4-point improvement from baseline) at week 4 and mean absolute change from baseline in gravimetrically-measured sweat production at week 4 • eligible patients were ≥9 years of age (patients <16 years were only recruited at us sites), had primary axillary hyperhidrosis for ≥6 months, gravimetrically-measured sweat production of ≥50 mg/5 min in each axilla, asdd item 2 score ≥4, and hyperhidrosis disease severity scale (hdss) grade ≥3 • patients were excluded for history of a condition that could cause secondary hyperhidrosis; prior surgical procedure or treatment with a medical device for axillary hyperhidrosis; treatment with iontophoresis within 4 weeks or treatment with botulinum toxin within 1 year for axillary hyperhidrosis; axillary use of nonprescription antiperspirants within 1 week or prescription antiperspirants within 2 weeks; new or modified psychotherapeutic medication regimen within 2 weeks; and/or treatment with medications having systemic anticholinergic activity, centrally acting alpha-2 adrenergic agonists, or beta-blockers within 4 weeks unless dose had been stable ≥4 months and was not expected to change figure 1. study design week 0 week 4 atmos-1 and atmos-2 target recruitment: 330 patients randomized in each study 2:1 gt vehicle gt, glycopyrronium tosylate patient-reported outcomes • ahpm (table 1) – the asdd consists of 4 items and was used for patients ≥16 years; patients <16 years of age completed a modified, 2-item version of the asdd, the asdd-c (table 1) – patients ≥16 years were additionally asked to complete 6 weekly impact items and a single-item pgic (table 1) • mean changes from baseline were summarized by descriptive statistics in the intent-to-treat (itt) population (all randomized subjects who were dispensed study drug) – for asdd item 2 (all patients) and asdd items related to the impact and bother of axillary sweating (items 3 and 4, respectively; patients ≥16 years of age), baseline was defined as the average of ≥4 days of data in the most recent 7 days prior to randomization – for the weekly impact items (patients ≥16 years of age), baseline was defined as the last available record prior to day 1 – as the pgic was only administered at the end of study treatment, there was no baseline value • missing values for asdd items 2 through 4 were not imputed; for weekly impact items, the last observation carried forward (locf) approach was used to impute missing values • an additional analysis was performed to assess the percent improvement from baseline to week 4 in asdd item 2, 3, and 4 scores table 1. axillary hyperhidrosis patient measures (ahpm)a axillary sweating daily diary (asdd)b instructions: the questions in the diary are designed to measure the severity and impact of any underarm sweating you have experienced within the previous 24 hour period, including nighttime hours. while you may also experience sweating in other locations on your body, please be sure to think only about your underarm sweating when answering these questions. please complete the diary each evening before you go to sleep. item 1 [gatekeeper] during the past 24 hours, did you have any underarm sweating? yes/no when item 1 is answered “no,” item 2 is skipped and scored as zero item 2 during the past 24 hours, how would you rate your underarm sweating at its worst?0 (no sweating at all) to 10 (worst possible sweating) item 3 during the past 24 hours, to what extent did your underarm sweating impact your activities?0 (not at all), 1 (a little bit), 2 (a moderate amount), 3 (a great deal), 4 (an extreme amount) item 4 during the past 24 hours, how bothered were you by your underarm sweating? 0 (not at all bothered), 1 (a little bothered), 2 (moderately bothered), 3 (very bothered), 4 (extremely bothered) axillary sweating daily diary-children (asdd-c)c instructions: these questions measure how bad your underarm sweating was last night and today. please think only about your underarm sweating when answering these questions. please complete these questions each night before you go to sleep. item 1 [gatekeeper] thinking about last night and today, did you have any underarm sweating? yes/no when item 1 is answered “no,” item 2 is skipped and scored as zero item 2 thinking about last night and today, how bad was your underarm sweating? 0 (no sweating at all) to 10 (worst possible sweating) weekly impact itemsb instructions: please respond “yes” or “no” to each of the following questions. a. during the past 7 days, did you ever have to change your shirt during the day because of your underarm sweating? yes/no b. during the past 7 days, did you ever have to take more than 1 shower or bath a day because of your underarm sweating? yes/no c. during the past 7 days, did you ever feel less confident in yourself because of your underarm sweating? yes/no d. during the past 7 days, did you ever feel embarrassed by your underarm sweating? yes/no e. during the past 7 days, did you ever avoid interactions with other people because of your underarm sweating? yes/no f. during the past 7 days, did your underarm sweating ever keep you from doing an activity you wanted or needed to do? yes/no patient global impression of change (pgic) itemb overall, how would you rate your underarm sweating now as compared to before starting the study treatment? 1 (much better), 2 (moderately better), 3 (a little better), 4 (no difference), 5 (a little worse), 6 (moderately worse), 7 (much worse) aasdd/asdd-c item 2 is a validated pro measure bfor use in patients ≥16 years of age cfor use in patients ≥9 to < 16 years of age results • a total of 697 patients were randomized and were asked asdd/asdd-c items 1 and 2 on a daily basis; 665 patients were ≥16 years of age and were asked asdd items related to the impact and burden of sweating on a daily basis (items 3 and 4, respectively), the weekly impact items on a weekly basis, and the pgic at end of treatment • demographic and baseline disease characteristics from the primary studies are presented in table 2 table 2. demographics and baseline disease characteristics atmos-1 atmos-2 vehicle (n=115) gt (n=229) vehicle (n=119) gt (n=234) demographics age (years), mean ± sd 34.0 ± 13.1 32.1 ± 11.2 32.8 ± 11.2 32.6 ± 10.9 age group, n (%) <16 years ≥16 years 6 ( 5.2) 109 (94.8) 5 ( 2.2) 224 (97.8) 10 ( 8.4) 109 (91.6) 11 ( 4.7) 223 (95.3) male, n (%) 55 (47.8) 99 (43.2) 59 (49.6) 113 (48.3) white, n (%) 94 (81.7) 182 (79.5) 102 (85.7) 192 (82.1) bmi (kg/m2), mean ± sd 27.2 ± 4.9 27.6 ± 5.8 28.4 ± 5.5 27.3 ± 5.0 baseline disease characteristics, mean ± sd years with primary axillary hyperhidrosis 16.0 ± 11.4 13.7 ± 10.4 15.9 ± 9.9 16.9 ± 11.1 sweat production (mg/5 min)a 170.3 ± 164.2 182.9 ± 266.9 181.9 ± 160.1 162.3 ± 149.5 asdd/asdd-c item 2 (severity) 7.1 ± 1.7 7.3 ± 1.6 7.2 ± 1.6 7.3 ± 1.6 asdd item 3 (impact)b 2.2 ± 0.9 2.4 ± 0.9 2.3 ± 1.0 2.5 ± 0.8 asdd item 4 (burden)b 2.4 ± 0.9 2.6 ± 0.8 2.5 ± 0.9 2.7 ± 0.9 agravimetrically-measured bmean baseline scores for asdd items 3 and 4 are based on all patients in the itt populations of atmos-1 and atmos-2 ≥16 years of age only baseline scores for items 2 to 4 were based on the average of ≥4 days of data in the most recent 7 days prior to randomization asdd, axillary sweating daily diary; asdd-c, asdd-children; bmi, body mass index; gt, topical glycopyrronium tosylate • the asdd item 2 responder rate (coprimary outcome; ≥4-point improvement) was significantly greater for gt-treated patients than for vehicle-treated patients in atmos-1 (53% vs 28%) and atmos-2 (66% vs 27%) (p<0.001 both studies) • improvement in axillary sweating severity (asdd/asdd-c item 2) was greater for gt-treated patients compared with vehicle-treated patients at every study week (figure 2) – after 4 weeks of treatment in atmos-1, scores improved 58% (-4.3 point change) in gt-treated patients and 35% (-2.5) in vehicle-treated patients compared with baseline – after 4 weeks of treatment in atmos-2, scores improved 67% (-4.9 point change) in gt-treated patients and 36% (-2.6) in vehicle-treated patients compared with baseline figure 2. percent improvement from baseline in axillary sweating severity (asdd/asdd-c item 2) scores by week vehiclegt vehiclegt 80 60 40 20 0 p er ce nt im pr ov em en t i n a xi lla ry s w ea tin g s ev er it y (a s d d /a s d d -2 it em 2 ) s co re s atmos-1 week atmos-2 0 1 2 3 4 80 60 40 20 0 week 0 1 2 3 4 67% 36%35% 58% data are representative of the intent-to-treat (itt) population; figures represent the change in scores in terms of percent improvement asdd item 2: during the past 24 hours, how would you rate your underarm sweating at its worst? 0 (no sweating at all) to 10 (worst possible sweating) asdd-c item 2: thinking about last night and today, how bad was your underarm sweating? 0 (no sweating at all) to 10 (worst possible sweating) asdd, axillary sweating daily diary; asdd-c, asdd-children; gt, topical glycopyrronium tosylate • improvement in scores related to the impact of axillary sweating (asdd item 3) scores was greater for gt-treated patients than vehicle-treated patients at every study week (figure 3) – after 4 weeks of treatment in atmos-1, scores improved by 63% (-1.5 point change) in gt-treated patients and 39% (-0.8) in vehicle-treated patients compared with baseline – after 4 weeks of treatment in atmos-2, scores improved by 72% (-1.7 point change) in gt-treated patients and 41% (-1.0) in vehicle-treated patients compared with baseline figure 3. percent improvement from baseline in scores related to the impact of axillary sweating (asdd item 3) by week vehiclegt vehiclegt 80 60 40 20 0 p er ce nt im pr ov em en t i n s co re s r el at ed to th e im pa ct of a xi lla ry s w ea tin g (a s d d it em 3 ) atmos-1 week atmos-2 0 1 2 3 4 80 60 40 20 0 week 0 1 2 3 4 72% 41% 63% 39% data are representative of the intent-to-treat (itt) population of patients ≥16 years of age; figures represent the change in scores in terms of percent improvement asdd item 3: during the past 24 hours, to what extent did your underarm sweating impact your activities? 0 (not at all), 1 (a little bit), 2 (a moderate amount), 3 (a great deal), 4 (an extreme amount) asdd, axillary sweating daily diary; gt, topical glycopyrronium tosylate • improvement in scores related to the bother of axillary sweating (asdd item 4) was greater in gt-treated patients than vehicle-treated patients at every study week (figure 4) – after 4 weeks of treatment in atmos-1, item 4 scores improved by 64% (-1.7 point change) in gt-treated patients and by 39% (-0.9) in vehicle-treated patients compared with baseline – after 4 weeks of treatment in atmos-2, item 4 scores improved by 72% (-1.9 point change) in gt-treated patients and by 41% (-1.0) in vehicle-treated patients compared with baseline figure 4. percent improvement from baseline in scores related to the bother of axillary sweating (asdd item 4) by week vehiclegt vehiclegt 80 60 40 20 0 p er ce nt im pr ov em en t i n s co re s r el at ed to th e b ot he r of a xi lla ry s w ea tin g (a s d d it em 4 ) atmos-1 week atmos-2 0 1 2 3 4 80 60 40 20 0 week 0 1 2 3 4 72% 41% 64% 39% data are representative of the intent-to-treat (itt) population of patients ≥16 years of age; figures represent the change in scores in terms of percent improvement asdd item 4: during the past 24 hours, how bothered were you by your underarm sweating? 0 (not at all bothered), 1 (a little bothered), 2 (moderately bothered), 3 (very bothered), 4 (extremely bothered) asdd, axillary sweating daily diary; gt, topical glycopyrronium tosylate • the proportion of patients who were negatively impacted by aspects of sweating (weekly impact items) decreased at week 4 for all patients regardless of treatment; the magnitude of the decrease was greater in patients treated with gt than with vehicle on all items, indicating greater improvement with gt treatment (figure 5) figure 5. proportion of patients answering ‘yes’ to weekly impact items 85.6% 32.1% a. needed to change shirt during the day 59.2% 23.7% b. needed ≥1 shower/bath a day 91.0% 38.8% c. felt less confident 98.5% 43.8% d. felt embarrassed 67.7% 17.9% e. avoided interactions 62.7% 13.8% f. kept from doing an activity 80.6% 50.5% a. needed to change shirt during the day 62.1% 43.1% b. needed ≥1 shower/bath a day 86.4% 58.7% c. felt less confident 93.2% 63.3% d. felt embarrassed 68.9% 34.9% e. avoided interactions 49.5% 21.1% f. kept from doing an activity 87.5% 22.5% a. needed to change shirt during the day 55.0% 14.9% b. needed ≥1 shower/bath a day 93.0% 33.3% c. felt less confident 96.0% 39.2% d. felt embarrassed 67.0% 15.8% e. avoided interactions 59.5% 10.8% f. kept from doing an activity 87.0% 55.0% a. needed to change shirt during the day 52.0% 24.8% b. needed ≥1 shower/bath a day 93.0% 61.5% c. felt less confident 97.0% 67.0% d. felt embarrassed 61.0% 34.9% e. avoided interactions 56.0% 31.2% f. kept from doing an activity baseline week 4 baseline week 4 80 100 60 40 20 0 80 100 60 40 20 0 80 100 60 40 20 0 80 100 60 40 20 0 p ro po rt io n of p at ie nt s an sw er in g “y es ” to w ee kl y im pa ct it em s (% ) gt vehicle p ro po rt io n of p at ie nt s an sw er in g “y es ” to w ee kl y im pa ct it em s (% ) a tm o s -2 a tm o s -1 data are representative of the intent-to-treat (itt) population of patients ≥16 years of age gt, topical glycopyrronium tosylate • following treatment in atmos-1 and atmos-2, 73.6% and 80.4% of gt-treated patients rated their axillary sweating as much or moderately better, compared with 38.2% and 40.6% of vehicle-treated patients, respectively (figure 6) • following treatment in atmos-1 and atmos-2, more vehicle-treated patients (29.4% and 36.5%, respectively) reported no difference or a little worsening in axillary sweating following treatment compared with those receiving gt (8.6% and 5.4%, respectively; figure 6) figure 6. distribution of patient responses to pgic vehiclegt 52.3% 17.6% 1 much better 21.3% 20.6% 2 moderately better 17.8% 32.4% 3 a little better 8.1% 24.5% 4 no difference 0.5% 4.9% 5 a little worse 0%0% 6 moderately worse 0% 0% 7 much worse vehiclegt 63.7% 26.0% 1 much better 16.7% 14.6% 2 moderately better 14.2% 22.9% 3 a little better 4.9% 32.3% 4 no difference 0.5% 4.2% 5 a little worse 0%0% 6 moderately worse 0% 0% 7 much worse 80 60 40 20 0 p ro po rt io n of p at ie nt r es po ns es to p g ic , % atmos-1 80 60 40 20 0 p ro po rt io n of p at ie nt r es po ns es to p g ic , % atmos-2 data are representative of the intent-to-treat (itt) population of patients ≥16 years of age pgic item: overall, how would you rate your underarm sweating now as compared to before starting the study treatment? 1 (much better), 2 (moderately better), 3 (a little better), 4 (no difference), 5 (a little worse), 6 (moderately worse), 7 (much worse) gt, topical glycopyrronium tosylate; pgic, patient global impression of change conclusions • after 4 weeks, gt-treated patients reported greater weekly average improvement than vehicle-treated patients on all asdd items (ie, severity, impact, and bother of axillary sweating on daily activities) that measured the daily burden of disease associated with axillary hyperhidrosis • at the end of treatment, fewer gt-treated patients reported the occurrence of the specific negative behaviors or feelings associated with their excessive axillary sweating than did vehicle-treated patients • following treatment, approximately 2-fold more gt-treated patients rated their axillary sweating as much or moderately better versus vehicle-treated patients • these additional results from atmos-1 and atmos-2 suggest that gt, if approved, has the potential to reduce the burden of disease for patients with axillary hyperhidrosis references 1. doolittle et al. arch dermatol res. 2016; 308 (10):743-9. 2. bahar et al. j am acad dermatol. 2016; 75(6):1126-33. 3. pariser et al. poster presented at: 13th annual maui derm for dermatologists; 2017; maui, hi. 4. nelson et al. development and validation of the axillary sweating daily diary: a patient-reported outcome measure to assess sweating severity. br j dermatol. [submitted] acknowledgements the authors would like to thank sheri fehnel, dana dibenedetti, and lauren nelson, from rti health solutions, as well as diane ingolia and christine conroy, from dermira, inc., for their work developing the pro questionnaire. these studies were funded by dermira, inc. medical writing support was provided by prescott medical communications group. all costs associated with development of this poster were funded by dermira, inc. author disclosures dmp: consultant and investigator for dermira, inc. aah: consultant for dermira, inc.; employee of the university of texas medical school, houston, which received compensation from dermira, inc. for study participation. jd: employee of dermira, inc. jq: employee of qst consultations. dag: consultant and investigator for dermira, inc. schedule of pro assessments in ecztra 1-3 patient-reported outcome measure dlqi poem eczema-related sleep nrs (weekly average) assessed daily with ediary assessed daily with ediary worst daily pruritus nrs (weekly average) baseline x x week 1 week 2 x x week 3 week 4 x x week 5 week 6 x x week 7 week 8 x x week 9 week 10 visit 5a week 11 week 12 x x week 13 week 14 visit 7a week 15 week 16 visit 1a visit 2a visit 3a visit 4a visit 6a visit 8a x x earliest possible time point for assessment figure 1. schedule of pro measure assessments in initial 16-week period introduction methods objective ● the objective of this analysis was to examine early changes in several pro measures across the ecztra 1/2 and ecztra 3 trials conclusions ● tralokinumab, with or without concomitant tcs, led to early (within 1−3 weeks) improvements in patient-relevant endpoints compared to placebo across the three trials ● ad severely impacts a patient’s quality of life; interventions with the potential to provide such early improvements are highly desirable ● concomitant use of tcs in ecztra 3 may explain why differences between tralokinumab and placebo were observed earlier in ecztra 1/2 ● the long-term resilience of pro measure improvements is being assessed in the ongoing ecztend trial for tralokinumab (nct03587805) ● these findings support the previously demonstrated superiority of tralokinumab 300 mg every two weeks when compared to placebo, over 16 weeks of treatment across multiple outcome measures, reflecting the signs and symptoms of ad ● atopic dermatitis (ad) is a chronic, inflammatory skin disease, with an estimated prevalence of between 2.1% and 4.9% in adults across north america, europe, and japan1 ● moderate-to-severe ad is characterized by symptoms including excessive dryness, scaling, red or inflamed skin, blisters or bumps, open sores or oozing, and intense itching.2 these symptoms can be severely debilitating to patients and their quality of life, resulting in sleep disturbance, pain, and depression2 ● the pathogenesis of ad is complex and multifactorial, combining skin barrier dysfunction and immune dysregulation, leading to chronic type 2 inflammation3,4 ● interleukin (il)-13, a key type 2 cytokine, has been identified as a key driver of the underlying inflammation of ad, with il-13 levels within lesional skin correlating with ad severity5-8 ● tralokinumab is a fully human monoclonal antibody which specifically neutralizes il-139 recent phase 3, placebo-controlled trials have investigated tralokinumab in the treatment of moderate-to severe ad as a monotherapy (ecztra 1, nct03131648; ecztra 2, nct03160885) and in combination with topical corticosteroids (tcs) [ecztra 3, nct03363854] efficacy results from these trials were promising, with significantly more patients achieving the primary endpoints of investigator’s global assessment (iga) score of 0 or 1 and eczema area and severity index (easi) score of 75 (a 75% reduction in easi score) at 16 weeks with tralokinumab versus placebo in all three studies ● it is important to assess the efficacy of tralokinumab in terms of patient-reported outcomes (pros), which are vital for providing insight on the real-life value of treatments for ad10 study design ● ecztra 1 and 2 were two identically designed, multinational, double-blind, randomized, placebo-controlled, 52-week trials ● ecztra 3 was a multinational, double-blind, randomized, placebo plus tcs-controlled 32-week trial ● all trials were conducted in adults with moderate-to-severe ad who were candidates for systemic therapy patients ● key inclusion criteria common for all trials were: 18 years of age; confirmed diagnosis of ad for 1 year; inadequate response to topical medications 1 year prior to screening; iga score of 3; and easi score of 12 at screening and 16 at baseline ● patients were randomized 3:1 to subcutaneous tralokinumab 300 mg or placebo every 2 weeks (ecztra 1/2) or 2:1 to subcutaneous tralokinumab 300 mg plus tcs or placebo every 2 weeks plus tcs (ecztra 3) for an initial 16 weeks ● rescue treatment in the form of topical and systemic medications was permitted in all trials to control intolerable ad symptoms patient-reported outcomes ● a series of pro measures were assessed in the three trials (figure 1) numeric rating scale (nrs) for worst daily pruritus (11-point scale with 0 being “no itch” and 10 being “worst itch imaginable”) [daily via an ediary] nrs for eczema-related sleep interference (11-point scale with 0 indicating that it “did not interfere” and 10 indicating that it “completely interfered”) [daily via an ediary] dermatology life quality index (dlqi): 10 items addressing a patient’s perception of the impact of their skin disease on different aspects of their daily life over the last week – patients scored the impact on each activity on a 4-point scale (where 0 is “not at all, not relevant” to 3 for “very much”) [bi-weekly to week 8, then at weeks 12 and 16] patient-orientated eczema measure (poem): consisting of seven items eac addressing a specific ad symptom over the last week (itching, sleep, bleeding, weeping, cracking, flaking, and dryness) – patients indicated the frequency of each experienced in the previous week to generate a total score (bi-weekly to week 8, then at weeks 12 and 16) dlqi and poem were answered electronically at the study site and all pro measures were reported prior to clinician assessments 2020 fall clinical dermatology conference, october 29-november 1, 2020, live virtual meeting early changes in patient-relevant endpoints in three tralokinumab pivotal phase 3 trials (ecztra 1−3) in adult patients with moderate-to-severe atopic dermatitis jonathan i. silverberg,1 michael cork,2 andreas wollenberg,3 norito katoh,4 louise abildgaard steffensen,5 azra kurbasic,5 christina kurre olsen,5 alexandra kuznetsova,5 marie louise østerdal,5 andreas westh vilsbøll,5 mette deleuran6 1department of dermatology, the george washington university school of medicine and health sciences, washington, dc, usa; 2sheffield dermatology research, department of infection, immunity & cardiovascular disease, faculty of medicine, dentistry & health, the university of sheffield, sheffield, uk; 3department of dermatology and allergy, ludwig-maximilian university, munich, germany; 4department of dermatology, kyoto prefectural university of medicine, kyoto, japan; 5leo pharma a/s, ballerup, denmark; 6department of dermatology, aarhus university hospital, aarhus, denmark safety ● adverse events were assessed at baseline and at each subsequent visit statistical analysis ● the changes in worst daily pruritus, eczema-related sleep interference, dlqi, and poem were assessed by a repeated measurements model, including baseline iga, region, and treatment-by-week interaction as factors and interaction between week and baseline value as covariates — change = treatment*week + baseline*week + region + baseline iga — data collected after permanent discontinuation or initiation of rescue medication were excluded patient-reported outcomes ● tralokinumab improved weekly average nrs worst daily pruritus from baseline compared with placebo by week 1 in ecztra 1 (–0.7 vs. –0.2; p0.001) and ecztra 2 (–0.7 vs. –0.3; p0.001), and week 3 in ecztra 3 (–2.6 vs. –2.0; p=0.003) (figure 2) ● tralokinumab reduced weekly mean eczema-related sleep interference from baseline compared with placebo by week 1 in ecztra 1 (–0.6 vs. –0.2; p0.001) and ecztra 2 (–0.7 vs. –0.2; p0.001) and week 2 in ecztra 3 (–2.3 vs. –1.9; p=0.037) (figure 3) characteristic ecztra 1 ecztra 2 ecztra 3 table 1. demographics and clinical characteristics of randomized patients at baseline q2w, every 2 weeks; scorad, scoring atopic dermatitis; sd, standard deviation. aincluding american indian or alaska native and native hawaiian or other pacific islander; bn=197; cn=195; dn=194; en=601; fn = 598; gn=591; hn=589; in=200; jn=592; kn=591; ln=584; mn=587; nn=586; on=126; pn=125; qn=252; rn=251; sn=250. week c h a n g e in w o rs t d a ily p ru ri tu s n r s tralokinumab q2w (n=601) placebo (n=197) 0 -2 -1 -3 -4 -5 0 2 3 4 5 6 7 8 9 10 11 12 13 15 1614 week c h a n g e in w o rs t d a ily p ru ri tu s n r s tralokinumab q2w (n=591) placebo (n=201) 0 -4 -2 -5 -3 -1 0 0 1 1 2 3 4 5 6 7 8 9 10 11 12 13 15 1614 week ecztra 3 c h a n g e in w o rs t d a ily p ru ri tu s n r s tralokinumab q2w + tcs (n=252) placebo + tcs (n=126) 0 a b c -2 -1 -4 -3 -5 1 2 3 4 5 6 7 8 9 10 11 12 13 15 1614 ** ** * * ** *** *** *** *** *** *** *** ****** ecztra 1 *** *** *** *** *** *** *** *** *** ** *** *** *** ****** *** ecztra 2 *** *** *** *** *** *** *** *** *** *** *** *** *** ****** *** figure 2. changes in worst daily pruritus nrs in ecztra 1, 2, and 3 a b c c ha ng e in ec ze m a -r el a te d s le ep n rs tralokinumab q2w (n=601) placebo (n=197) 0 -4 -2 -3 -1 -5 0 -2 -4 -3 -1 -5 0 ecztra 1 *** *** *** *** *** *** *** *** ** ** ** ** ** **** ecztra 2 c ha ng e in ec ze m a -r el a te d s le ep n rs tralokinumab q2w (n=591) placebo (n=201) 0 *** *** *** *** *** *** *** *** *** *** *** *** *** *** ****** ecztra 3 c ha ng e in ec ze m a -r el a te d s le ep n rs 0 -2 -4 -5 -3 -1 week 0 1 2 3 4 5 6 7 8 9 10 11 12 13 15 1614 week 1 2 3 4 5 6 7 8 9 10 11 12 13 15 1614 week 1 2 3 4 5 6 7 8 9 10 11 12 13 15 1614 *** ** ** *** *** *** *** *** *** *** *** *** ****** tralokinumab q2w + tcs (n=252) placebo + tcs (n=126) *** figure 3. changes in daily eczema-related sleep nrs in ecztra 1, 2, and 3 in ecztra 1, 2, and 3 p0.05; **p0.01; ***p0.001. data collected after permanent discontinuation of investigational medicinal product or initiation of rescue medication not included. in case of no post-baseline assessments before initiation of rescue medication, the week 2 change will be imputed as 0. ecztra 2 b c h a n g e in d lq i tralokinumab q2w (n=591) placebo (n=201) 0 2 4 6 8 10 12 1614 ****** ****** *** *** 0 -2 -4 -8 -12 -14 -6 -10 a week c h a n g e in d lq i tralokinumab q2w (n=601) placebo (n=197) 0 2 4 6 8 10 12 1614 *** *** *** *** *** ** 0 -2 -4 -8 -12 -14 -6 -10 ecztra 1 week c ****** ****** ** * week ecztra 3 c h a n g e in d lq i tralokinumab q2w + tcs (n=252) placebo + tcs (n=126) 0 -2 -4 -8 -12 -14 -6 -10 0 2 4 6 8 10 12 1614 figure 4. changes in dlqi in ecztra 1, 2, and 3 *p0.05; **p0.01; ***p0.001. data collected after permanent discontinuation of investigational medicinal product or initiation of rescue medication not included. in case of no post-baseline assessments before initiation of rescue medication, the week 1 change will be imputed as 0. *p<0.05; **p<0.01; ***p<0.001. data collected after permanent discontinuation of investigational medicinal product or initiation of rescue medication not included. in case of no postbaseline assessments before initiation of rescue medication, the week 1 change will be imputed as 0. *p0.05; **p0.01; ***p0.001. data collected after permanent discontinuation of investigational medicinal product or initiation of rescue medication not included. in case of no postbaseline assessments before initiation of rescue medication, the week 2 change will be imputed as 0. week c h a n g e in p o em tralokinumab q2w (n=591) placebo (n=201) 0 -2 -4 -6 -10 -14 -8 -12 0 2 4 6 8 10 12 1614 *** *** ****** *** *** ecztra 2 a week c h a n g e in p o em tralokinumab q2w (n=601) placebo (n=197) -14 0 2 4 6 8 10 12 1614 ecztra 1 *** *** ****** *** *** week ecztra 3 c h a n g e in p o em tralokinumab q2w + tcs (n=252) placebo + tcs (n=126) 0 -4 -10 -14 -12 -8 -2 -6 0 2 4 6 8 10 12 1614 ** *** ****** *** *** figure 5. changes in poem score in ecztra 1, 2, and 3 patient characteristics ● 802, 794, and 380 patients were randomized in ecztra 1, 2, and 3, respectively. ● patient demographics were well balanced between randomized groups (table 1) results safety ● in the 16-week period, the overall safety of tralokinumab was comparable to placebo ● the incidence of 1 adverse event was similar between tralokinumab and placebo patients in all three trials (76.4% vs. 77.0% in ecztra 1, 61.5% vs. 66.0% in ecztra 2, and 71.4% vs. 66.7% in ecztra 3) ● the majority of adverse events were mild or moderate in severity ● tralokinumab reduced mean dlqi compared with placebo in ecztra 1 (–4.4 vs. –2.5; p0.001), ecztra 2 (–4.7 vs. –2.2; p0.001), and ecztra 3 (–8.9 vs. –7.3; p=0.011) by week 2 (figure 4) avisit with efficacy assessment after baseline. ● tralokinumab reduced mean poem compared with placebo in ecztra 1 (–4.0 vs. –1.3; p0.001), ecztra 2 (–4.6 vs. –1.6; p0.001), and ecztra 3 (–7.9 vs. –5.9; p=0.006) by week 2 (figure 5) ● mean improvements from baseline for dlqi and poem reached minimally clinical important difference of 4 at week 2 for tralokinumab disclosures jonathan i. silverberg has received grants, personal fees, or nonfinancial support from abbvie, anaptysbio, arena, asana, boehringer ingelheim, celgene, dermavant, dermira, lilly, galderma, glaxosmithkline, kiniksa, leo pharma, medimmune, menlo, novartis, pfizer, regeneron, and sanofi. michael cork is an investigator and/or consultant for astellas, boots, dermavant, galapagos, galderma, hyphens, johnson & johnson, leo pharma, l’oréal, menlo therapeutics, novartis, oxagen, pfizer, procter & gamble, reckitt benckiser, regeneron, and sanofi genzyme. andreas wollenberg has received grants, personal fees, or nonfinancial support from abbvie, almirall, beiersdorf, bioderma, chugai, galapagos, galderma, hans karrer, leo pharma, lilly, l’oreal, maruho, medimmune, novartis, pfizer, pierre fabre, regeneron, santen, and sanofi-aventis norito katoh is an advisor, speaker, or investigator for abbvie, lilly, leo pharma, maruho, mitsubishi tanabe, kyowa kirin, taiho, regeneron, and sanofi. louise abildgaard steffensen, azra kurbasic, christina kurre olsen, alexandra kuznetsova, marie louise østerdal, and andreas westh vilsbøll are employees of leo pharma. mette deleuran has received research support, consulting/advisory board agreements, and/or honoraria for lecturing from abbvie, almirall, galapagos, leo pharma, lilly, meda, novartis, pfizer, pierre fabre, regeneron, and sanofi gen. the tralokinumab ecztra 1, 2, and 3 studies were sponsored by leo pharma. references 1. barbarot s et al. allergy 2018; 73: 1284–1293. 2. silverberg ji et al. ann allergy asthma immunol 2018; 121: 340–347. 3. guttman-yassky e et al. semin cutan med surg 2017; 36: 100–103. 4. czarnowicki t et al. j allergy clin immunol 2019; 143: 1–11. 5. szegedi k et al. j eur acad dermatol venereol 2015; 29: 2136–2144. 6. tsoi lc et al. j invest dermatol 2019; 139: 1480–1489. 7. bieber t. allergy 2020; 75: 54–62. 8. pavel ab et al. j am acad dermatol 2020; 82: 690–699. 9. popovic b et al. j mol biol 2017; 429: 208–219. 10. mercieca-bebber r et al. patient relat outcome meas 2018; 9: 353–367. skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 25 rising derm stars® abstracts preventative medicine in dermatologic care: providing immunization education and convenient pneumococcal immunizations for patients receiving immunosuppressive therapy ashleigh workman, do1, josh lindsley, ms-iii2, nathaniel webb, mph3, thaddeus miller, drph, mph4, erica stockbridge, phd4, jean charles, do1, michael carletti, do1,2, stephen weis, do1,2,5 1department of dermatology, medical city weatherford, weatherford, tx 2texas college of osteopathic medicine, university of north texas health science center (unthsc), fort worth, tx 3department of biostatistics & epidemiology, school of public health (sph), unthsc, fort worth, tx 4department of health behavior & health systems, sph, unthsc, fort worth, tx 5john peter smith hospital, jps health network, fort worth, tx immunosuppressive therapies increase risk of infections 2-fold when compared to naive individuals;1 however, an observational study found that only 4% of patients with psoriasis who were on or planned to start immunosuppressive therapy were immunized with pneumococcus.2 factors positively influencing vaccination uptake include having vaccines available same day in clinic and education about vaccines. negative influences include no recommendation from the treating clinician and no insurance.3 failure to vaccinate occurs by overlooking indication and an uncertainty as to who is responsible for vaccination.4 since the early 2000’s, vaccinations have been offered in pharmacies. this could result in additional confusion regarding vaccination responsibility. as a result of not being immunized, patients on immunosuppressive medications experience higher rates of preventable infections. we observed that many of our patients’ immunizations were incomplete and sought to increase immunization uptake through a quality improvement (qi) project beginning in fall 2019. we evaluated the project’s approach of providing education with immediate onsite immunization availability relative to standard care to determine if vaccination uptake per cdc guidelines5 can be increased. we compared acceptance of cdc recommended pneumococcal immunization for patients on immunosuppressive therapy who were and were not subject to the qi project at the 2 urban dermatology clinics. patients in the comparison group were under the care of other dermatologists. all patients in the qi group were educated on benefits of immunizations and offered immediate immunizations. those who had never received the pcv13 or ppsv23 were introduction methods skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 26 table 1. immunization status by group and time point, including unadjusted and adjusted column percentages. n=201. unadjusted column percentages qi group (n=146) comparison group (n=55) pvalue immunization status initial observation final observation initial observation final observation no immunization 69.9 (61.9, 76.8) 13.7 (9.0, 20.4) 60.0 (46.4, 72.2) 60.0 (46.4, 72.2) <0.001 partially immunized 18.5 (13.0, 25.7) 47.9 (39.9, 56.1) 32.7 (21.5, 46.3) 32.7 (21.5, 46.3) fully immunized 11.6 (7.3, 18.0) 38.4 (30.8, 46.6) 7.3 (2.7, 18.1) 7.3 (2.7, 18.1) adjusted column percentages* qi group (n=146) comparison group (n=55) pvalue immunization status initial observation final observation initial observation initial observation no immunization 66.3 (59.8, 72.7) 16.1 (10.9, 21.3) 62.1 (53.6, 71.6) 62.1 (53.6, 71.6) <0.001 partially immunized 26.1 (21.3, 30.9) 43.2 (37.0, 49.4) 28.7 (21.4, 36.0) 28.7 (21.4, 36.0) fully immunized 7.7 (3.9, 11.4) 40.6 (0.34, 0.47) 9.2 (5.0, 13.4) 9.2 (5.0, 13.4) *adjusted column percentages are the average predicted probabilities calculated based on results of a multivariable ordered logit model; probabilities multiplied by 100 and expressed as percentages. defined as unimmunized. patients who had received either vaccination were partially immunized. patients who received both were completely immunized. we collected demographics and immunization status for all patients. using stata 14.2 [statacorp, college station, tx], we compared immunization status at baseline and final observations for patients in the qi and comparison groups using a multivariable ordered logit model, and used multiple logistic regression to examine receipt of a vaccination within the qi group. the qi (n=146) and comparison groups (n=55) did not differ significantly on sociodemographic or clinical characteristics, including baseline immunization. after adjusting for patient characteristics, baseline immunization rates for fully, partially, and unimmunized patients were 9.2%, 28.7%, and 62.1% for the comparison group and 7.7%, 26.1%, and 66.3% for the qi group, respectively. immunization statuses within the comparison group did not change over time, but at final observation 40.6%, 43.2%, and 16.1% of the qi group were fully, partially, and unimmunized, respectively (table 1; p<0.001). of patients in the qi group eligible for vaccination at baseline, 81% (105/129) received a vaccination. there was a significant association between immunization and insurance; uninsured patients in the qi group had significantly lower odds of receiving a vaccination (table 2; p=0.015). providing patients on immunosuppressive regimens with education and immediate vaccination access in a dermatology clinic. results conclusion skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 27 table 2. unadjusted and adjusted associations between receipt of one or more pneumonia vaccinations during the qi project and characteristics of persons in the qi group who were not already fully immunized (n=129). unadjusted associations adjusted associations variable total n=129 column % (95% ci) vaccine not received n=24 column % (95% ci) vaccine received n=105 column % (95% ci) p-value odds ratio (or) 95% confidence interval of or p-value gender female 64.3 (55.6, 72.2) 66.7 (45.4,82.8) 63.8 (54.1, 72.5) 0.792 1.00 (ref) male 35.7 (27.8, 44.4) 33.3 (17.2, 54.5) 36.2 (27.5, 45.9) 1.06 0.35 3.24 0.917 age <=34 22.5 (16.0, 30.6) 25.0 (11.4, 46.4) 21.9 (14.9, 31.0) 0.610 1.00 (ref) 35-44 22.5 (16.0, 30.6) 33.3 (17.2, 54.5) 20.0 (13.3, 28.9) 0.81 0.20 3.37 0.777 45-54 19.4 (13.4, 27.2) 12.5 (3.9, 33.2) 21.0 (14.1, 29.9) 3.79 0.56 25.67 0.172 55-64 25.6 (18.7, 33.9) 20.8 (8.7, 42.1) 26.7 (19.0, 36.1) 1.40 0.26 7.64 0.699 >=65 10.1 (5.9, 16.7) 8.3 (2.0, 28.8) 10.5 (5.8, 18.1) 1.06 0.15 7.50 0.955 primary insurance private 13.2 (8.3, 20.3) 8.3 (2.0, 28.8) 14.3 (8.7, 22.5) 0.007 1.00 (ref) public (medicare or medicaid) 52.7 (44.0, 61.3) 45.8 (27.0, 65.9) 54.3 (44.6, 63.7) 0.89 0.15 5.22 0.893 county program 24.0 (17.4, 32.3) 16.7 (6.2, 37.7) 25.7 (18.2, 35.0) 1.10 0.15 8.06 0.927 uninsured 10.1 (5.9, 16.7) 29.2 (14.2, 50.5) 5.7 (2.6, 12.3) 0.07 0.01 0.59 0.015 patient used translator no 82.9 (75.3, 88.6) 91.7 (71.2, 98.0) 81.0 (72.2, 87.4) 0.208 1.00 (ref) yes 17.1 (11.4, 24.7) 8.3 (2.0, 28.8) 19.0 (12.6, 27.8) 7.14 0.91 56.31 0.062 count of prior office-based contacts (all provider specialties) 0-3 visits 30.2 (22.8, 38.8) 33.3 (17.2, 54.5) 29.5 (21.5, 39.1) 0.89 1.00 (ref) skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 28 4-8 visits 29.5 (22.2, 38.0) 33.3 (17.2, 54.5) 28.6 (20.7, 38.1) 0.62 0.17 2.28 0.473 9-14 visits 26.4 (19.4, 34.7) 20.8 (8.7, 42.1) 27.6 (19.8, 37.1) 0.85 0.20 3.68 0.829 >=15 visits 14.0 (8.9, 21.2) 12.5 (3.9, 33.2) 14.3 (8.7, 22.5) 0.74 0.14 3.82 0.717 visit type at initial observation initial 20.2 (14.0, 28.1) 25.0 (11.4, 46.4) 19.0 (12.6, 27.8) 0.512 1.00 (ref) follow-up 79.8 (71.9, 86.0) 75.0 (53.6, 88.6) 81.0 (72.2, 87.4) 1.98 0.52 7.51 0.317 number of indications other than medication(s) and age† count variable‡ 0.81 (0.64, 0.97) 0.75 (0.35, 1.14) 0.82 (0.64, 1.00) 0.746 0.98 0.50 1.91 0.952 immunosuppresive medications used prior to initial observation no 16.3 (10.8, 23.8) 12.5 (3.9, 33.2) 17.1 (11.0, 25.7) 0.578 1.00 (ref) yes 83.7 (76.2, 89.2) 87.5 (66.8, 96.1) 82.9 (74.3, 89.0) 0.40 0.08 2.06 0.271 † includes heart disease (congestive heart failure or coronary artery disease), diabetes, lung disease (chronic obstructive pulmonary disease or asthma), chronic renal failure, or being a current smoker. possible range 0-5, actual range 0-4. ‡ unadjusted numbers represent mean significantly increased uptake of recommended pneumococcal immunization. widespread use of this practice could reduce vaccine preventable illness and improve population health. furthermore, there is a clear need for additional interventions targeting uninsured patients. conflict of interest disclosures: none funding: none corresponding author: dr. stephen weis, d.o. health science center medical city weatherford department of dermatology 1301 throckmorton street unit 1803 fort worth, texas email: stephen.weis@unthsc.edu references: 1. r gluck, t. and u. muller-ladner (2008). "vaccination in patients with chronic rheumatic or autoimmune diseases." clin infect dis 46(9): 1459-1465. 2. bonhomme, a., et al. (2017). "[vaccination status in psoriasis patients on immunosuppressant therapy (including biologics)]." ann dermatol venereol 144(2): 92-99. 3. bacurau agm, francisco pmsb. reasons for non-vaccination against influenza among older adults with hypertension in brazil: a crosssectional study. sao paulo med j. 2020;138(4):322-325. doi:10.1590/15163180.2020.0042.r1.15052020 4. lejri-el euchi, h., et al. (2019). "vaccination against influenza and pneumococcal infections in patients with autoimmune disorders under biological therapy: coverage and attitudes in patients and physicians." eur j intern med. 5. rubin, l. g., et al. (2014). "2013 idsa clinical practice guideline for vaccination of the immunocompromised host." clin infect dis 58(3): 309-318. mailto:stephen.weis@unthsc.edu skin march 2018 volume 2 issue 2 copyright 2018 the national society for cutaneous medicine 96 featured article utility of food patch testing in the evaluation and management of irritable bowel syndrome grace h. shin md a , michael s. smith md mba b , butros toro md c , adam c. ehrlich md mph a , sanjana luther md c , deena midani md a , inki hong md c , michael stierstorfer md d,e,f a section of gastroenterology, department of medicine, lewis katz school of medicine at temple university b section of gastroenterology, department of medicine, icahn school of medicine at mount sinai c lewis katz school of medicine at temple university d east penn dermatology, pc e university of pennsylvania school of medicine f ibs centers for advanced dermatology food allergy testing, llc abstract background. irritable bowel syndrome (ibs) is a functional gastrointestinal (gi) disorder of unknown etiology. objective. we sought to investigate whether specific type 4 food allergens identified by skin patch testing, when eliminated from the diet, alleviate symptoms of ibs. methods. in this case series, skin patch testing was performed on 60 ibs patients using an extensive panel of type 4 food allergens after which food avoidance diets directed by the patch test results were implemented. questionnaires assessing abdominal pain/discomfort and global improvement in ibs symptoms were used to assess one month and three or more month outcomes. results. there were statistically significant improvements in abdominal pain/discomfort and in global ibs symptoms after one month and again at an average of 7.6 months of patch test-guided food avoidance. conclusions. sustained improvement with avoidance of type 4 food allergens identified by skin patch testing suggests a role for delayed-type food hypersensitivities in the pathogenesis of some cases of ibs. a subset of patients whose ibs symptoms resolve completely may be better characterized as having a newly proposed disease, allergic contact enteritis (ace). skin march 2018 volume 2 issue 2 copyright 2018 the national society for cutaneous medicine 97 irritable bowel syndrome (ibs) is the most common gastrointestinal (gi) disorder presenting to a primary care office, accounting for up to 50% of visits associated with a gi problem 1 . it is characterized by abdominal pain coinciding with altered stool form or frequency, with a complex microbiome-brain-gut axis 2 . despite the high prevalence of ibs, its pathophysiology is not fully understood and patients often undergo a variety of tests to rule out other diseases prior to being diagnosed with ibs. recent observations of the pathophysiology of ibs suggest various causes for the symptoms 3 . mounting evidence points to the presence of inflammation in the intestinal lining and proinflammatory mediators in the bloodstream in many individuals with ibs symptoms 4,5,6 . an association of ibs in some individuals with quiescent inflammatory bowel disease or postinfectious gastroenteritis 7 also supports a role for inflammation, but most ibs sufferers have had neither. furthermore, there has been increased interest in looking at the potential inflammatory effects of food in the gi tract 8,9,10 , as up to 50% of ibs sufferers report that foods aggravate their symptoms 11 . the preponderance of investigation of food allergy in ibs has focused on the antibody-mediated humoral (type 1, 2 and 3 allergy) arm of the immune system. both a landmark consensus report considering all aspects of food allergy 12 issued by the national institutes of allergy and infectious disease and a comprehensive position statement on ibs management 13 by an american college of gastroenterology task force fail to invoke an immunologic mechanism for the pathogenesis of ibs, by default suggesting a poorly understood non-immunologic mechanism for food intolerance. in contradistinction to skin prick and scratch tests, antibody assays and other serologic tests used to investigate humoral immunity, skin patch testing is a common dermatologic procedure used to investigate the cellmediated (type 4 allergy) arm of the immune system. patch testing is routinely employed to detect causes of allergic contact dermatitis, a t lymphocyte-mediated type 4 eczematous allergic reaction in the skin. many foods have the potential to cause allergic contact dermatitis 14 . a proof-ofconcept case series in 2013 used food patch testing to investigate a role for a cellmediated immune mechanism in ibs 15 . in that study, 27% of the 51 individuals with ibs symptoms benefited from limited type 4 food allergen patch testing and subsequent dietary avoidance of the foods identified by the testing. by performing skin patch testing with an expanded panel of type 4 food allergens on patients with physician-diagnosed ibs and/or who fulfill the rome iii criteria 16 , followed by assessment of their ibs symptoms one month and again three or more months after implementation of an elimination diet guided by the patch test results, our study further probes the question whether food-related type 4 hypersensitivities may cause ibs symptoms. this prospective case series was conducted in a secondary care community-based setting. all participants were self-referred over a 36 month period, had physicianintroduction methods skin march 2018 volume 2 issue 2 copyright 2018 the national society for cutaneous medicine 98 diagnosed ibs and/or met the rome iii criteria for ibs and presented expressly for the food patch testing on a fee-for-service basis. ibs subtype was determined upon presentation by self-reported historically predominant symptom. duration of ibs symptoms was self-reported and was rounded to the nearest year for purposes of data collection. if duration was reported as a range of years, the average between the shorter and longer estimate was used and if reported as “at least x” years, “x” was the duration used for data collection. patients who were pregnant; were known to have an allergy to adhesive tape or any of the food allergens used in the study; had a severe skin rash; had symptoms that had a known cause other than ibs; or were on active treatment with any systemic immunosuppressive medications were excluded from the study. skin patch testing was initiated using an extensive non-fda-approved panel of 117 to 121 type 4 food allergens (table 1) identified in the literature 14 , most utilizing standard formulations 17 or available from reputable patch test manufacturers (brial allergen gmbh, greven, germany; chemotechnique diagnostics, vellinge, sweden). the freeze-dried vegetable formulations were derived from unpublished data. standard skin patch test procedure protocols 14 were used affixing the patches to the upper aspect of the back. table 1. type 4 food allergens used in the patch testing and the total number of questionable or positive reactions for each allergen at 72 or 96 hours. allergen # of positive results allergen # of positive results 1-malic acid 1 formic acid 1 2-tert-butyl-4methoxyphenol (bha) 1 garlic 0 acetoin 0 garlic powder 1 aconitic acid 0 geraniol 0 almond oil 0 geranyl acetate 1 amaranth (red #2) 5 ginger oil 1 anethole 0 glyceryl tributyrate 0 anise seed oil 0 green food color (yellow #5, blue #1) 2 arabic gum 0 guar gum 0 artichoke 0 horseradish 28 asparagus 2 hydroxycitronellal 0 aspartame 1 isoeugenol 2 azorubine 3 karaya gum 1 balsam of peru 6 leeks 1 bay leaf oil 3 lettuce 1 beeswax 0 linalyl acetate 0 benzaldehyde 1 menthol 1 benzoic acid 7 methyl anthranilate 0 benzoin gum 0 mushroom 4 benzoyl peroxide 25 nickel sulfate hexahydrate 8 benzyl benzoate 0 octyl gallate 11 blue food color 0 oil of bergamot 0 skin march 2018 volume 2 issue 2 copyright 2018 the national society for cutaneous medicine 99 (blue #1) brilliant black 0 oil of chamomile 1 calcium disodium edta 0 oil of cinnamon 1 capsicum 1 oil of clove 1 caraway oil 0 oil of eucalyptus 0 carmine 29 oil of rose 0 carnauba wax 1 oil of rosemary 0 carrot 0 onion 1 carrot seed oil 0 paraben mix 2 carvone 1 patent blue 1 acetaldehyde 0 pectin 0 celery 1 pinene alpha 2 chicory 0 polysorbate 80 2 chives 0 potassium bromate 3 chlorophyll 0 potassium sorbate 2 allyl isothiocyanate 0 propionic acid 0 cinnamic aldehyde 1 propyl gallate 1 cinnamon bark oil 36 quinolone yellow 0 citral 1 red food color (red #3, red #40) 7 citric acid 1 saccharin 1 citronellal 0 salicylaldehyde 0 aluminum sulfate 0 sesame oil 0 corn 1 sesquiterpene lactone mix 1 coumarin 1 sodium benzoate 1 cucumber 1 sodium bisulfate 8 d limonene 1 sodium bisulfite 27 dl-alpha-tocopherol 0 sodium diphosphate 0 dodecyl gallate 6 sodium glutamate 1 endive 2 sodium nitrite 2 erythrosin (red #3) 2 sorbic acid 2 ethyl acetate 0 strawberry aldehyde 2 ethyl butyrate 1 tartrazine 0 ethyl vanillin 1 tomato 2 vanilla extract 1 vanillin 0 eucalyptol 0 wool alcohol 2 eugenol 0 yellow food color (yellow #5) 0 2,6-di-tert-butyl-4cresol (bht) 1 polysorbate 60 1 butyric acid 0 propylene glycol 0 diallyl disulfide 0 terpineol alpha 0 nutmeg 0 # of positive results, all patch test results that were questionable or positive by standard patch test reading convention. 18 table 1 (continued) skin march 2018 volume 2 issue 2 copyright 2018 the national society for cutaneous medicine 100 following patch test application on day 1, two follow up visits occurred on day 3 and either day 4 or 5. on day 3, patches were removed and the initial results were read by one board-certified dermatologist according to a standard grading system 18 . interpretation of patch tests included no reaction; questionable reaction consisting of macular erythema; weak reaction consisting of erythema and slight edema; or strong reaction consisting of erythema and marked edema. on day 4 or 5, the final patch test reading was performed to account for delayed reactions up to 96 hours. patients were informed of the results and advised to avoid ingestion of all foods that elicited a questionable or positive patch test response, with information about the foods distributed and reviewed. those with questionable or positive patch tests at 72 or 96 hours were invited to participate in an investigational review board (irb)-approved study by completing a questionnaire (chart 1) that assessed both compliance with dietary avoidance and response of gastrointestinal symptoms to these changes. abdominal pain/discomfort was assessed at baseline and at one month with the difference at these two junctures used to measure effect of dietary avoidance on these symptoms. global ibs symptom improvement at one month was assessed by a single 0 to 10 self-rated scale. the questionnaire was to be completed and returned by each patient along with the questionnaire informed consent after avoidance of the identified allergens for one month. patients received $20 compensation for completion and return of both. a second irb-approved long term follow-up questionnaire assessing compliance with the dietary avoidance, abdominal pain/discomfort and global improvement (chart 2) was mailed to individuals with ibs who reported symptom improvement at the one month interval. it was accompanied by an irb-approved follow-up study invitation, informed consent, $10 non-binding cash payment and a stamped, addressed return envelope. these materials were mailed three or more months after implementation of the avoidance diet. each participant’s responses after one month from the first questionnaire were provided on the followup questionnaire as a frame of reference for the long term follow-up answers. data from the follow-up questionnaire was subsequently compared to those same endpoints from the initial one month questionnaire. total duration from initiation of the avoidance diet also was recorded for each completed long term follow-up questionnaire. statistical analysis of data collected from the study questionnaires was performed with microsoft excel. mean abdominal pain/discomfort and mean global improvement scores were reported with one standard deviation. for comparison of mean abdominal pain/discomfort and improvement in global ibs symptoms after 1 month and after 3 months of identified allergen avoidance, a paired sample t-test was used as the data followed a normal distribution, with a value of p < 0.05 being considered statistically significant. all authors had access to the study data and had reviewed and approved the final manuscript. skin march 2018 volume 2 issue 2 copyright 2018 the national society for cutaneous medicine 101 ibs food avoidance questionnaire instructions: please read the accompanying informed consent. if you choose to complete this questionnaire, sign and date the informed consent, sign and da te this completed questionnaire, and mail them back to us in the enclosed stamped, addressed envelope. please do so within 2 weeks after avoiding the foods in question for 1 month. we will send you a check for $20 within 4 weeks after receiving your completed informed consent and questionnaire. your full name: ________________ age: ____ sex: female male race: caucasian african-american hispanic asian mixed other ______________________ prefer not to answer have you or any blood-related family members ever had eczema, asthma, hay fever, other seasonal allergies or allergies to dogs, cats, pollen, mold, grass or other environmental allergens? (circle one) yes no not sure dermatologist who performed your food patch testing: _______________________________ foods/food additives to which you had a positive skin test (list all): 1. __________________________ 2. __________________________ 3. __________________________ 4. __________________________ in the past month, how well were you able to avoid the foods/food additives listed above? completely partially not at all not sure please explain, if necessary: _______________________________________ on a scale of 0 to 10, before you had the food patch testing done, how severe, on average, was your belly pain/discomfort? (0 = no symptoms and 10 = very severe) (circle your answer) 0 1 2 3 4 5 6 7 8 9 10 on a scale of 0 to 10, after you avoided the food(s) to which you reacted with the patch tests for one month, how severe, on average, was your belly pain/discomfort? (0 being no symptoms and 10 being very severe) (circle your answer) 0 1 2 3 4 5 6 7 8 9 10 by the end of the one month food avoidance period, how much improvement in your overall ibs symptoms did you have? (0 = no improvement, 10 = great improvement) (circle your answer) 0 1 2 3 4 5 6 7 8 9 10 which of your ibs symptoms, of the following, have you mostly had problems with? (circle one) constipation diarrhea neither both, at various times on average, about how many times a day did you have bowel movements before you underwent the patch testing and avoided the foods in question? (circle one) 0 to 1 1 to 2 2 to 3 3 or more or: very variable, can't choose any of the above choices after avoiding the foods in question for one month, about how many times a day do you have bowel movements? (circle your answer) 0 to 1 1 to 2 2 to 3 3 or more or: very variable, can't choose any of the above choices if you did experience improvement in your ibs symptoms, about how long after starting to avoid the foods did you notice the improvement? (circle your answer) within a few days, or less within a week or two not until the end of the month please write any comments about the testing or your experience that you feel are relevant: chart 1. questionnaire to assess ibs symptoms one month after starting the patch testguided food avoidance diet. skin march 2018 volume 2 issue 2 copyright 2018 the national society for cutaneous medicine 102 ibs food avoidance follow-up questionnaire instructions: please read the accompanying informed consent. if you choose to complete this questionnaire, sign and date the informed consent, complete the questionnaire (where appropriate, circle your answers), and mail them both back to us in the enclosed stamped, addressed envelope at your earliest convenience. enclosed please find $10 for your efforts. your full name: ____________________________ age: _______ foods/food additives to which you had a positive skin test: 5. __________________________ 6. __________________________ 7. __________________________ 8. __________________________ 9. ___________________________ as a reminder, on a scale of 0 to 10, before you had the food patch testing done, you reported to us that the severity, on average, of your belly pain/discomfort was (0 = no symptoms and 10 = very severe): 0 1 2 3 4 5 6 7 8 9 10 you also previously had reported to us that after one month, the success you had with avoiding the foods in question was: completely partially not at all not sure 1. now, at this point in time, how well have you been able to avoid the foods/food additives listed above? completely partially not at all not sure please explain, if necessary: _______________________________________ 2. now that it has been at least several months since you underwent the food patch testing, on a scale of 0 to 10, how severe, o n average, has your belly pain/discomfort been? (0 being no symptoms and 10 being very severe) 0 1 2 3 4 5 6 7 8 9 10 as a reminder, on a scale of 0 to 10, after one month of avoidance of the food(s) in question, you reported to us that the improvement in your overall ibs symptoms was (0 = no improvement and 10 = great improvement): 0 1 2 3 4 5 6 7 8 9 10 3. now that it has been at least several months since you underwent the food patch testing, on a scale of 0 to 10, how much improvement in your overall ibs symptoms have you had? (0 = no improvement, 10 = great improvement) 0 1 2 3 4 5 6 7 8 9 10 please write any comments about the food patch testing or your experience that you feel are relevant: chart 2. follow-up questions to assess ibs symptoms and dietary compliance 3 or more months after start of the patch test-guided avoidance diet, for patients who reported improvement one month after starting the same diet. skin march 2018 volume 2 issue 2 copyright 2018 the national society for cutaneous medicine 103 eighty-five consecutive patients underwent the patch testing and were eligible for participation in the study. one patient had no patch test reactions and 24 did not return the initial one month questionnaire. sixty patients were included for this study by virtue of having at least one questionable or positive patch test reaction and subsequently completing and returning their initial questionnaire informed consent and study questionnaire. fifty-six of the patients (93.3%) were caucasian, two (3.3%) were african-american and one (1.7%) each were hispanic and asian. subcategories of ibs included 46.7% diarrhea-predominant, 20.0% constipation-predominant, and 33.3% mixed. table 2 summarizes the raw data and overall results for all 60 study participants as well as results for the subgroups of 40 patients reporting improvement at one month and at three or more months (subgroup a), 10 patients reporting improvement at one month but not returning their long term follow-up questionnaire (subgroup b), and 10 patients reporting no improvement at one month (subgroup c). fifty (83.3%) patients reported at least slight to marked improvement in their abdominal pain/discomfort and in their global ibs symptoms after one month of patch testdirected food avoidance. accounting for all 60 patients including those who reported no improvement, there was a mean decrease in the severity of abdominal pain/discomfort of 4.1±2.6 points (p<0.001) and a mean improvement in global ibs symptoms vs. baseline of 6.0±3.2 points (p<0.001) at one month of food avoidance. there were no statistically significant differences in improvement of abdominal pain/discomfort or global improvement among the ibs subtypes. of the 50 patients who reported improvement one month after start of the patch test-directed avoidance diet, 40 (80.0%) completed and returned the long term follow-up questionnaire and accompanying informed consent (table 2, subgroup a). 92.5% were caucasian, 5.0% african american, and 2.5% hispanic. mean duration of food avoidance was 7.6 ± 3.9 months. the improvement in abdominal pain/discomfort at baseline vs. at three or more months was 4.7 (p<0.001). mean global ibs symptom improvement at three or more months was 7.3 ± 2.8 (p<0.001). table 3 and table 4 provide an overview of global ibs symptom improvement and abdominal pain/discomfort scores at one month and at three or more months of patch testguided dietary avoidance, respectively. results skin march 2018 volume 2 issue 2 copyright 2018 the national society for cutaneous medicine 104 table 2. raw data and overall results for all study participants. subgroup a patients who reported improvement with avoidance diet at one month and at three or more months abdominal pain/discomfort dietary compliance global symptom improvement time to improvement sex age ibs duration (years)/ ibs type total # of ? or 1+ or > patches total # of 1+ or > patches base -line at 1 month at 3 or more months at 1 month at 3 or more months at 1 month at 3 or more months f 35 18/d 3 1 9 1 7 p p 8 7 d m 30 3/d 1 1 7 3 3 p p 7 7 w f 42 20/d 2 2 7 2 2 p p 9 9 w m 64 1/d 4 2 7 2 2 c c 7 9 w f 76 31/d 4 2 10 3 0 c c 10 10 w m 35 20/c 7 1 10 4.5 3.5 c p 6 8 w f 46 20/d 3 1 10 1 0 c c 10 10 d f 43 12/m 10 6 8 1 3 p p 9 10 w f 40 2/c 4 3 8 5 4 p p 8 10 w f 11 2/d 6 4 10 0 0 p p 10 10 d m 31 1/m 6 1 5 1 2 c c 8 8 m f 47 15/d 8 4 6 2 1 c c 8 9 d f 59 20/d 6 1 7 2 2 p p 7 9 w m 45 7/d 7 3 6 1 3 p p 10 9 d f 75 12/m 6 2 2 1 2 p p 4 4 w m 35 14/d 5 4 4 2 3 p p 5 7 w f 57 1/d 4 1 10 6 5 p p 6 7 w f 21 5/m 1 1 7 1 2 c c 10 8 d f 55 3/c 4 2 7 2 7 c p 2 5 d f 65 47/d 8 1 8 3 2 p p 7 8 d f 42 25/c 4 1 6 3 5 p p 5 0 d f 13 2/m 3 3 8 1 3 p p 10 9 d f 52 13/c 7 2 8 0 3 c p 10 8 w f 48 8/m 6 2 7 1 1 p p 9 10 w f 46 10/m 4 3 4 1 1.5 p p 2 9 w f 48 3/m 4 3 7 3 2.5 p p 8 2.5 m f 57 10/m 5 0 10 6 1 c p 6 10 m f 13 9/c 6 2 8.5 7 1.5 p c 3.5 7 w subgroup a totals/ averages f 45 2/d 3 2 8 3 5 c p 8 7 w f 29 6/d 7 2 8 5 2 p p 4 9 m f 42 20/m 2 0 8 4 2 c c 7 8 w f 20 5/d 7 1 8 1 1 p p 8 9 w f 41 20/d 6 3 8 6 4 p p 5 2 m f 52 7/c 2 1 8.5 1 0 c c 10 10 d f 37 6/m 2 1 7 5 5 c p 5 6 w f 31 7/d 3 1 10 1 2 c p 10 10 w f 59 1/d 8 6 10 2 7 p p 7 7 d f* 30 2/m 4 1 8 2 8* p n 9 0* d f 65 13/d 5 2 3 0 1 p p 3 3 d f 27 22/m 3 1 8 6 3 p p 3 3 m 34 f 6 m 42.7 ± 16.0 11.1 ± 9.8 4.8 ± 2.1 2.1 ± 1.4 7.5 ± 1.9 2.5 ± 1.9 2.8 ± 2.0 15 c 25 p 9 c 30 p 1 n 7.1 ± 2.5 7.3 ± 2.8 14 d 20 w 6 m skin march 2018 volume 2 issue 2 copyright 2018 the national society for cutaneous medicine 105 subgroup b patients who reported improvement at one month but did not return follow-up questionaire subgroup b totals/ averages f 24 15/m 3 0 8 5 p 5 m f 16 4/d 4 0 7 5 p 9 w f 41 15/c 3 1 8 4 c 8 m f 42 20/m 6 1 5.5 0 p 8 d f 33 10/d 2 1 6 1 c 10 d m 59 15/d 9 4 6 1 p 10 d f 37 2/m 4 3 9 4 p 7 w f 27 10/m 5 1 7 3 c 6 d f 45 15/m 9 2 10 5 c 5 m m 61 35/m 5 5 6 5 p 3 w 8 f 2 m 38.5 ± 14.4 14.1 ± 9.2 5.0 ± 2.4 1.8 ± 1.7 7.3 ± 1.5 3.3 ± 2.0 4 c 6 p 7.1 ± 2.3 4 d 3 w 3 m subgroup c patients who reported no improvement with avoidance diet at one month subgroup c totals/ averages f 52 35/d 1 0 8 8 c 0 m 64 10/d 4 0 3 3 p 0 m 64 2/d 7 1 4 4 c 0 f 24 2/c 7 2 8 8 c 0 f 59 5/m 1 1 1 0 c 0 f 28 10/c 5 1 4 1 c 1 f 22 3/d 2 1 4 4 c 0 m 44 10/c 2 2 7 7 c 0 f 24 2/c 3 1 8 8 p 0 f 56 40/d 4 1 10 10 p 0 7 f 3 m 43.7 ± 17.6 11.9 ± 14.0 3.6 ± 2.2 1.0 ± 0.6 5.7 ± 2.7 5.3 ± 3.4 7 c 3 p 0.1 ± 0.3 complete study group totals/ averages 49 f 11 m 42.2 ± 15.9 11.7 ± 10.4/ 28 d 12 c 20 m 4.6 ± 2.2 1.8 ± 1.4 7.2 ± 2.1 3.1 ± 2.4 26 c 34 p 6.0 ± 3.2 f, female; m, male; ibs type: c, constipation-type; d, diarrhea-type; m, mixed-type; ?, questionable; >, greater than; dietary compliance: p, partial; c, complete; n, not at all; time to improvement: d, days; w, 1 to 2 weeks; m, end of month. * this patient reported pain/discomfort and overall improvement at one month of patch test-directed food avoidance. at some time after the first month her ibs symptoms reverted to baseline, prompting selfabandonment of this diet and start of a low fermentable oligosaccharide, disaccharide, monosaccharide, and polyol (fodmap) diet 19 which resulted in sustained improvement. for data collection purposes for this study, her baseline and one month follow-up data were used as she reported. since her long term follow-up selfassessment scores were attributable to the low fodmap diet, they were discarded for purposes of this study in favor of her baseline pain/discomfort score (8) and assignment of a score of 0 for her long term overall improvement score, to more accurately reflect the patch test-guided avoidance diet outcome. table 2 (continued) skin march 2018 volume 2 issue 2 copyright 2018 the national society for cutaneous medicine 106 table 3. global ibs symptom improvement scores with patch test-guided food avoidance diet. number of patients / percentage reported improvement in global ibs symptoms vs. baseline at one month n=60 at three or more months *n=40 none (0 to <2) 10/16.7% 1 / 2.5% slight (2 to <5) 8 / 13.3% 5 / 12.5% moderate (5 to <8) 17 / 28.3% 9/ 22.5% marked (8 to 10) 25 / 41.7% 25 / 62.5% n, number of patients *includes all patients who reported improvement at one month and returned their three or more month followup questionnaire. table 4. abdominal pain/discomfort scores with patch test-guided avoidance diet. number of patients / percentage abdominal pain/ discomfort baseline n=60 at one month n=60 at three or more months *n=40 0 to <2 1 / 1.7% 19 / 31.7% 11 / 27.5% 2 to <5 8 / 13.3% 19 / 31.7% 22 / 55.0% 5 to <8 20 / 33.3% 12 / 20.0% 7 / 17.5% 8 to 10 31 / 51.7% 10 / 16.7% 0 based on a 0 to 10 self-reported rating scale with 0=no abdominal pain/discomfort and 10=very severe abdominal pain/discomfort. n, number of patients *includes all patients who reported improvement at one month and returned their three or more month follow-up questionnaire. skin march 2018 volume 2 issue 2 copyright 2018 the national society for cutaneous medicine 107 approximately 50% of patients with ibs report that foods aggravate their symptoms 11 , spawning great interest in the role of food allergies in its pathogenesis. until recently, attention has focused on igemediated immediate-type (type 1) hypersensitivity and igg antibody-mediated mechanisms but there has been insufficient evidence to support the routine recommendation of such diagnostic testing 12 . in contrast, the aforementioned 2013 proofof-concept study 15 and our study investigate a role for cell-mediated (type 4) immunity in ibs pathogenesis. the 2013 study was, to our knowledge, the first to investigate the utility of patch testing a panel of type 4 food allergens for ibs. food allergens generating a type 4 allergic reaction mostly are different substances than type 1 food allergens (i.e. peanuts, shellfish, milk proteins, etc.). the 2013 study showed partial or complete overall improvement after one week of patch test-directed food avoidance in 27.5% of participants tested to 28 to 40 foods. stierstorfer, et al posit that the same or a similar allergic contact response as elicited in the skin by contact with the allergenic foods during patch testing likely occurs in the intestinal lining when the same foods are ingested, resulting in inflammation that triggers ibs symptoms, and newly described as allergic contact enteritis (ace). limitations of that study include short duration of the avoidance diet and follow-up, non-blinded participation, and absence of a control group. additionally, placebo effect is most prevalent for conditions such as ibs where primarily subjective outcome measures are available 20 , with a prevalence of up to 40% in ibs 21 . in a 1999 report 22 , spiller analyzed 25 randomized, placebocontrolled ibs clinical trials, observing that placebo effect begins to diminish after about 12 weeks. he concluded that the optimum length of an ibs trial be greater than three months. in the absence of blinding and of a control group in our study, its extended follow-up of over seven months vs. the 2013 study allows for better assessment of durability of response and validity of its results. forty (80.0%) of the 50 patients who benefited after one month of food avoidance returned their long term follow-up questionnaires. the average follow-up of 7.6 ± 3.9 months in these 40 patients surpasses spiller’s minimum ibs study duration recommendation of at least 3 months. the decrease in abdominal pain/discomfort and improvement in overall ibs symptom scores were largely sustained over this time period, thus supporting a role for delayed-type food hypersensitivities in the pathogenesis of ibs symptoms, independent of placebo effect. the retrospective manner in which the selfassessments were reported in this study introduces the potential for recall bias, another variable that could affect results. the presence and direction of bias by any given individual cannot be known, making it difficult to determine any effect it may have had. mechanistically, our findings support the hypothesis that in some patients who fulfill the diagnostic criteria for ibs, a very similar inflammatory response as elicited in the skin (allergic contact dermatitis) by the patch tests likely occurs in the intestinal mucosa discussion skin march 2018 volume 2 issue 2 copyright 2018 the national society for cutaneous medicine 108 when culprit foods are ingested, thereby disrupting motility and causing ibs-like symptoms. in the subset of ibs sufferers whose symptoms have remitted completely over a sustained period with patch testguided food avoidance, these results further support the existence of the newly proposed disease, allergic contact enteritis (ace), its symptoms mimicking those of ibs. many of the type 4 food allergens used in this study are commonly encountered in the average american diet. some of the most reactive allergens are also some of the most ubiquitous, including cinnamon bark oil; carmine, a red food dye; sodium bisulfite, a preservative; and benzoyl peroxide, used to bleach flour and cheese. examples of food components that less often elicited patch test skin reactions are pinene alpha, naturally occurring in parsley, carrots, parsnips and celery, and d-limonene, present in citrus. dietary avoidance of the foods identified by patch testing proved to be challenging. thirty (75.0%) of the 40 participants with sustained improvement at 3 or more months reported partial avoidance. twenty-seven elected to comment, reporting as reasons for partial rather than complete avoidance: difficulty avoiding the multiple or ubiquitous allergens to which they reacted; uncertainty when their food was not selfprepared; and/or difficulty when processed food labels did not specifically identify each ingredient; i.e., “artificial flavors”, “natural flavors”, “spices”. many of these same participants correlated minor or major flares of their ibs symptoms when straying from their avoidance diet. in summary, the findings of this expanded proof-of-concept study suggest the possible pathophysiology for some cases of ibs. dietary avoidance of trigger foods identified by patch testing may offer a cost effective, non-pharmacologic approach to treat patients who carry this diagnosis. further study is needed to investigate the hypothesis that delayed-type food hypersensitivities may contribute to or mimic ibs. randomized trials in which ibs patient cohorts are blinded to their patch test results and assigned blinded diets with food allergen(s) avoided or not avoided for a period of time, then crossed over, would further mitigate the role of placebo in future validation studies. small bowel biopsy in patients who benefit from patch test-guided food avoidance while on the avoidance diet and after food rechallenge could definitively investigate the hypothesized correlation between skin inflammation elicited by food patch testing and intestinal mucosal inflammation elicited by ingestion of the same food(s). strategically timed cytokine profile assays in search of a proinflammatory state may be similarly informative in a less invasive manner. it will also be of interest to compare efficacy of patch test-guided type 4 food allergen elimination diets with that of a diet low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols (fodmaps), another dietary intervention recently demonstrated to improve ibs symptoms 19 . acknowledgements: the authors thank bruce brod, md for support in preparation of the manuscript. conflict of interest disclosures: michael b. stierstorfer, md is the director of the ibs centers for advanced food allergy testing, llc; has a canadian patent: food patch testing for irritable bowel syndrome and undifferentiated gastrointestinal disorders; and has submitted patent applications to united states patent and trademark office and the equivalent agency in europe for the same. for the remaining authors, there are no conflicts of interest. funding: none. skin march 2018 volume 2 issue 2 copyright 2018 the national society for cutaneous medicine 109 corresponding author: michael b. stierstorfer, md 2101 market street, suite 2802 philadelphia, pa 19103 215-557-7430 (office) 215-661-0302 (fax) mstierstorfer@eastpennderm.com references: 1. wilson a, longstreth gf, knight k, et al. quality of life in managed care patients with irritable bowel syndrome. managed care interface. 2004;17:24-28, 34. 2. mayer ea. gut feelings: the emerging biology of gut-brain communication. nat rev neurosci. 2011;12:453-463. 3. spiller r. irritable bowel syndrome: new insights into symptom mechanisms and advances in treatment. f1000research, 2016; available at: https://www.ncbi.nlm.nih.gov/pmc/ar ticles/pmc4856111/. accessed june 25, 2016. 4. chadwick vs, chen w, shu d, et al. activation of the mucosal immune system in irritable bowel syndrome. gastroenterology. 2002;122:17781783. 5. tornblom h, lindberg g, nyberg b, veress b. full-thickness biopsy of the jejunum reveals inflammation and enteric neuropathy in irritable bowel syndrome. gastroenterology. 2002;123:1972-1979. 6. o'mahony l, mccarthy j, kelly p, et al. lactobacillus and bifidobacterium in irritable bowel syndrome: symptom responses and relationship to cytokine profiles. gastroenterology. 2005;128:541-551. 7. grover m, herfarth h, drossman da.the functional–organic dichotomy: postinfectious irritable bowel syndrome and inflammatory bowel disease–irritable bowel syndrome. clin 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gastroenterol. 2009;104:s1-35. 14. rietschel rl, fowler jf. fisher's contact dermatitis. hamilton, ontario (canada):bcdecker; 2008. 15. stierstorfer mb, sha ct, sasson m. food patch testing for irritable bowel syndrome. j am acad dermatol. 2013;68:377-384. 16. rome foundation. guidelines--rome iii diagnostic criteria for functional gastrointestinal disorders. j gastrointestin liver dis. 2006;15:307312. 17. degroot ac. patch testing. the netherlands:acdegroot publishing; 2008. 18. marks jg, belsito dv, deleo md, et al. north american contact dermatitis group patch test results for the detection of delayed-type hypersensitivity to topical allergens. j am acad dermatol. 1998;38:911-918. 19. halmos ep, power va, shepherd sj, et al. a diet low in fodmaps reduces symptoms of irritable bowel syndrome. gastroenterology. 2014;146:67-75.e5. 20. hrobiartsson a, gotzsche pc. is the placebo powerless? an analysis of clinical trials comparing placebo with no treatment. n engl j med. 2001;344:1594-1602. 21. ford ac, moayyedi p. meta-analysis: factors affecting placebo response rate in the irritable bowel syndrome. aliment pharmacol ther. 2010;32(2):144-158. 22. spiller rc. problems and challenges in the design of irritable bowel syndrome clinical trials: experience from published trials. am j med. 1999;107:91s-97s acknowledgements: medical writing support was provided by prescott medical communications group (chicago, il) with financial support from ortho dermatologics; ortho dermatologics is a division of bausch health us, llc • presented at the fall clinical dermatology conference for pas and nps • june 9-11, 2023 • orlando, fl background and rationale � for acne vulgaris, the recommended first-line treatments are topical benzoyl peroxide (bpo) or retinoids as monotherapy, or in combination with each other and/or an antibiotic1 � cutaneous irritation or dermatitis—either irritant (occurs rapidly post-contact) or allergic (a less common, delayed immunemediated response)—may limit use of bpo or retinoids2,3 � idp-126 polymeric mesh gel (clindamycin phosphate 1.2%/bpo 3.1%/adapalene 0.15%) is the first triple-combination, fixed-dose topical acne product in development and it addresses major acne pathophysiological processes � in a phase 2 and two phase 3 studies in participants with moderate-to-severe acne, idp-126 resulted in over 70% reductions of inflammatory and noninflammatory lesions at week 12, with good safety/tolerability4 objectives � to assess dermal irritation/sensitization and safety of idp-126 gel in two phase 1 studies � to compare irritancy of idp-126 gel and commercially available bpo 2.5%/ adapalene 0.3% gel in one phase 1 study of healthy participants methods � two phase 1, randomized, evaluatorblinded, within-participant, dermal safety studies enrolled healthy participants aged ≥18 years (figure 1) � patches were applied to participants’ upper back multiple times over 6-8 weeks (ript) or every 24 hours for 21 days (cipt; figure 1) • participants in each study received all treatments � endpoints comprised sensitization potential (allergic; ript only), mean cumulative/total irritation scores, and treatment-emergent adverse events (teaes) • clinical grading of irritation consisted of a combination of letter and numerical grades (see table at bottom in figure 2) figure 1. study designs for the ript and cipt studies2,5,6 repeat insult patch test (ript) idp-126 gel vehicle gel saline 0.9% (negative control) patch applications (for 48-72 h; 3x/wk)b in induction and challenge phases, patches were applied 10 times to left or right upper back over 6-8 weeks. if re-challenge a was required, patches were applied 11 additional times. all who received study treatment safety population all who completed challenge phase sensitization population all who completed induction phase cumulative irritancy population study populations determines the potential of a topical treatment to induce sensitization (allergic potential) via repeated applications cumulative irritancy patch test (cipt) patch applications (once daily)b over 21 days, patches were applied once daily to the left or right upper back for 24h. all who received study treatment safety population study populations evaluates a topical treatment’s irritancy potential as a result of direct damage to the epidermal cells (without involvement of allergic or immunologic mechanism) via repeated applications idp-126 gel vehicle gel saline 0.9% (negative control) sodium lauryl sulfate 0.5% (positive control) bpo 2.5%/adap 0.3% gel (active comparator) aparticipants were only re-challenged to a study material if there were signs suggestive of contact sensitization observed at any challenge evaluations or at the investigator’s discretion. btreatment patch placement was randomized for each participant. adap, adapalene; bpo, benzoyl peroxide; idp-126, clindamycin phosphate 1.2%/benzoyl peroxide 3.1%/adapalene 0.15%. dermal irritation, sensitization, and safety of fixed-dose triple-combination clindamycin phosphate 1.2%/benzoyl peroxide 3.1%/adapalene 0.15% gel in healthy participants zoe d draelos, md,1 emil a tanghetti, md,2 linda stein gold, md,3 leon h kircik, md,4-6 neal bhatia, md,7 joshua a zeichner, md,4 jeffrey l sugarman, md, phd8 1dermatology consulting services, pllc, high point, nc; 2center for dermatology and laser surgery, sacramento, ca; 3henry ford hospital, detroit, mi; 4icahn school of medicine at mount sinai, new york, ny; 5indiana university medical center, indianapolis, in; 6physicians skin care, pllc, dermresearch, pllc, and skin sciences, pllc, louisville, ky; 7therapeutics clinical research, san diego, ca; 8university of california, san francisco, ca figure 2. mean cumulative irritation scores (ript cumulative irritancy population; cipt safety population) 0.37 0.07 0.05 0 1 2 3 m ea n s co re ± s d 1.29 0.32 0.30 1.17 1.96 0 1 2 3 *** *** *** *** *** g re at er ir ri ta tio n cipt (n=44)ript (n=209) idp-126 vehicle gel saline 0.9% idp-126 sls 0.5% bpo 2.5%/ adap 0.3% vehicle gel saline 0.9% ***p<0.001 vs idp-126 gel. saline 0.9%=negative control; sls 0.5%=positive control; bpo 2.5%/adap 0.3%=active comparator. bpo 2.5%/adap 0.3%, benzoyl peroxide 2.5%/adapalene 0.3% gel; cipt, cumulative irritancy patch test; idp-126, clindamycin phosphate 1.2%/benzoyl peroxide 3.1%/adapalene 0.15% gel; ript, repeat insult patch test; sd, standard deviation; sls, sodium lauryl sulfate. figure 3. normalized total irritation scores (cipt safety population) 264 66 63 232 401 0 100 200 300 400 500 600 *** *** *** n or m al iz ed t ot al ir ri ta tio n s co re no significant irritation slightly irritating moderately irritating highly irritating idp-126 vehicle gel saline 0.9% sls 0.5% cipt (n=44) to determine irritation classification of each treatment, a normalized total score for each patch was calculated by multiplying the mean total irritation score by a factor of 10 • 0–49 = no significant irritation • 50–199 = slightly irritating • 200–449 = moderately irritating • 450–630 = highly irritating bpo 2.5%/ adap 0.3% ***p<0.001 vs idp-126 gel. saline 0.9%=negative control; sls 0.5%=positive control; bpo 2.5%/adap 0.3%=active comparator. bpo 2.5%/adap 0.3%, benzoyl peroxide 2.5%/adapalene 0.3% gel; cipt, cumulative irritancy patch test; idp-126, clindamycin phosphate 1.2%/benzoyl peroxide 3.1%/adapalene 0.15% gel; sls, sodium lauryl sulfate. results participants � a total of 279 participants were randomized � ript populations: safety, n=234; cumulative irritancy, n=209; sensitization, n=206 • a total of 210 participants completed the induction phase and received the challenge phase applications, and 206 (88.0%) completed the study � cipt population: safety, n=45 • a total of 44 participants were included in the irritation analysis, and 42 (93.3%) completed the study � in both studies, the mean age of participants was ~55 years, and the majority were female (ript: 71.4%; cipt: 77.8%), black (ript/cipt: ~68%), and non-hispanic (89.3%; 91.1%), with a fitzpatrick skin type of iv-vi (65.4%; 80.0%) dermal sensitization and irritation � overall, irritation with idp-126 was moderate and not clinically significant � ript: no participants had investigatorconfirmed sensitization to any treatments • as expected, mean cumulative irritation scores were higher with idp-126 vs vehicle or saline 0.9% (p<0.001, both; figure 2) • idp-126 gel, vehicle gel, and saline 0.9% were all classified as not causing clinically significant irritation � cipt: idp-126 had a score of “moderately irritating,” but was significantly less irritating than bpo 2.5%/adapalene 0.3% (p<0.001; figures 2 and 3) • the highest normalized total irritation score was observed for bpo 2.5%/ adapalene 0.3% gel, which was significantly greater than idp-126 (401 vs 264; p<0.001; figure 3) adverse events � in both studies, most teaes were of mild-moderate severity, and <3% of participants discontinued due to aes/teaes (table 1) � no teaes/serious aes were related to treatment � there was no contact dermatitis or discontinuation of patch applications due to irritation table 1. treatment-emergent adverse events (safety populations) n (%) ript (n=234) cipt (n=45) participants reporting any teae 4 (1.7) 1 (2.2) participants reporting any saea 1 (0.4) 1 (2.2) participants discontinuing due to ae/teaeb 3 (1.3) 1 (2.2) deaths 1 (0.4)c 0 severity of teaes mild 2 (0.9) 0 moderate 1 (0.4) 1 (2.2) severe 1 (0.4) 0 relationship to study drug related 0 0 unrelated 4 (1.7) 1 (2.2) anone of the participants had saes that were considered treatment related. bdiscontinuing from the study or study drug; none of the aes were deemed related to treatment. cpatient died during hospitalization for suspected covid-19; no proof of death could be obtained. ae, adverse event; cipt, cumulative irritancy patch test; ript, repeat insult patch test; sae, serious adverse event; teae, treatment-emergent adverse event. conclusions � in two phase 1 studies, fixed-dose, triplecombination idp-126 polymeric mesh gel had moderate irritancy and no confirmed sensitization (ie, allergic potential) in healthy participants � additionally, idp-126 gel demonstrated significantly less irritation versus commercially available, branded bpo 2.5%/adapalene 0.3% gel � idp-126 was well tolerated, with most teaes of mild-moderate severity � overall, idp-126 demonstrated good safety and tolerability, mirroring the phase 2 and phase 3 study results4 references 1. zaenglein, a.l. j am acad dermatol. 2016;74(5):945-73. 2. nguyen, h.l. clin rev allergy immunol. 2019;56(1):41-59. 3. foti, c. dermatol ther. 2015;28(5):323-9. 4. stein gold, l. j am acad dermatol. 2022;87(3):sab50. 5. jordan, w.p. contact dermatitis. 1980;6(2):151-2. 6. berger, r.s. j toxicol, cutan ocul toxicol. 1982;1(2):109-115. author disclosures zdd has received funding from ortho dermatologics. eat has served as speaker for novartis, ortho dermatologics, sun pharma, lilly, galderma, abbvie, and dermira; served as a consultant/clinical studies for hologic, ortho dermatologics, and galderma; and is a stockholder for accure. lsg has served as investigator/consultant or speaker for ortho dermatologics, leo pharma, dermavant, incyte, novartis, abbvie, pfizer, sun pharma, ucb, arcutis, and lilly. lhk has acted as an investigator, advisor, speaker, and consultant for ortho dermatologics. nb has served as advisor, consultant, and investigator for abbvie, almirall, biofrontera, bi, brickell, bms, epi health, ferndale, galderma, incyte, isdin, j&j, larocheposay, leo pharma, ortho dermatologics, regeneron, sanofi, sunpharma, verrica, and vyne. jaz has served as advisor, consultant, or speaker for abbvie, allergan, dermavant, dermira, epi health, galderma, incyte, johnson and johnson, l’oreal, ortho dermatologics, pfizer, procter and gamble, regeneron, sun pharma, ucb, unilever, and vyne. jls is a consultant for ortho dermatologics, bausch health, regeneron, sanofi, verrica, and pfizer. numerical grade 0 no evidence of irritation 1 minimal erythema; barely perceptible 2 definite erythema, readily visible; or minimal edema; or minimal papular response 3 erythema, edema, and/or papules; vesicular eruption; or strong spreading reaction letter grade (converted to numbers) 0 slight glazed appearance 1 marked glazing 2 glazing with peeling and cracking 3 glazing with fissures; film of dried serous exudate; or small petechial erosions cumul ative irritation score numerical gr ade + let ter gr ade ma x worst score = 6 skin july 2019 volume 3 issue 4 copyright 2019 the national society for cutaneous medicine 253 brief articles cvid-associated granulomatous dermatosis resembling sarcoidosis jeanette r. zambito1, pooja r. shah1, glynis scott1, andrew evans1, lisa a. beck1 1university of rochester medical center, school of medicine and dentistry, rochester, ny our patient is a 75-year-old male former smoker with a past medical history of common variable immunodeficiency (cvid) on weekly subcutaneous human immunoglobulin, hypertension, hyperlipidemia, coronary artery disease, and chronic kidney disease, who presented to the hospital with new-onset weakness and ataxia, as well as urinary and fecal incontinence. he had been diagnosed with cvid four months prior to presentation due to three recurrent episodes of pneumonia over a two month period. he had no prior history of other autoimmune or inflammatory disease. review of systems was notable for low-grade fevers and intermittentlyproductive cough for several months. dermatology was consulted for evaluation of a pruritic full-body rash that had been present for approximately one year. previous treatment with ultrapotent topical steroids did not provide any benefit; however, a sevenday oral prednisone taper resulted in partial improvement of pruritus and mental status. skin examination was notable for diffuse pink to red papules with overlying fine white scale (figure 1), as well as isolated linear excoriations on the trunk and extremities. additionally, there were blanchable red to introduction common variable immunodeficiency (cvid) is a disorder of the adaptive immune system predominantly characterized by hypogammaglobulinemia and variable t-cell abnormalities. patients classically present with recurrent sinopulmonary infections, but interstitial lung disease, autoimmunity, and lymphoproliferative disorders are also common. approximately 10% of cvid patients are reported to have noncaseating granulomatous disease that is indistinguishable from sarcoidosis on pathology; it most commonly affects the lungs, lymph nodes, and liver. we present the case of a 75-year-old male with known cvid who presented with granulomatous dermatosis on the trunk and extremities in the setting of progressive cognitive impairment, new-onset cough with ground glass opacities on chest computed tomography in the setting of stable mediastinal lymphadenopathy, and the presence of granulomas on prior bone marrow biopsy, initially suggesting the diagnosis of sarcoidosis. though clinically and histologically similar, it is important to make the distinction between cvid-associated granulomatous disease and sarcoidosis in order to select appropriate treatment. abstract skin july 2019 volume 3 issue 4 copyright 2019 the national society for cutaneous medicine 254 violaceous macules with minimal scale on the bilateral palms and soles. skin biopsies were performed on the left arm and back and revealed multiple noncaseating dermal granulomas associated with a sparse cuff of lymphocytes (figure 2). given his clinical presentation, immunocytochemical staining against treponema pallidum (monoclonal antibody to t. pallidum) was performed to rule out syphilis and was negative. further staining with cd30 showed scattered reactive cd30-positive cells, thus ruling out clonal lymphoproliferative disorders. of note, a prior bone marrow biopsy showed noncaseating granulomatous disease with negative fungal and mycobacterial stains (figure 3). workup was notable for a normocytic anemia (hemoglobin 10.8 g/dl), thrombocytopenia (platelet count 117 k/mcl), elevated creatinine (1.71 mg/dl), and elevated alkaline phosphatase level (201 iu/l). erythrocyte sedimentation rate was within normal limits, but c-reactive protein was elevated at 25 mg/l. prior serum igg, iga, and igm levels were all below detection. blood and urine cultures were negative. chest ct revealed prominent mediastinal lymph nodes (unchanged from earlier cts), in addition to new patchy, nodular parenchymal disease within the right upper lobe. head ct and non-contrast magnetic resonance imaging showed chronic small-vessel disease, mild generalized cerebral volume loss, and cerebellar atrophy, but no acute intracranial abnormalities or features consistent with sarcoidosis. cerebrospinal fluid studies were unremarkable and ruled out infectious or inflammatory causes of encephalitis. the patient was referred to immunology for further management. the patient was started on prednisone 40mg daily and infliximab 5mg/kg intravenous every 6 weeks (following induction with 5mg/kg at weeks 0, 2, and 6) for suspected neurosarcoidosis. the patient’s skin findings improved dramatically with this treatment regimen, while he also became increasingly alert and responsive to stimuli. however, his cough was persistent and his memory remained poor. two months after starting the above regimen, the patient was readmitted to the hospital with fevers to 103.3ºf and altered mental status. he developed acute respiratory failure and was diagnosed with pneumocystis jirovecii pneumonia, with prednisone and infliximab likely serving as contributing factors. despite adequate treatment with a 21-day course of trimethoprimsulfamethoxazole, the patient failed to return to baseline and required close outpatient monitoring. he was readmitted with fevers of unknown origin (temperature 103.1 ºf) and altered mental status. figure 1. skin examination was notable for diffuse pink to erythematous papules with overlying fine white scale, as well as isolated linear excoriations on the trunk and extremities. skin july 2019 volume 3 issue 4 copyright 2019 the national society for cutaneous medicine 255 during this third admission, he underwent repeat bone marrow biopsy and was found to have epstein barr virus-positive hodgkin’s lymphoma. he received a course of high dose steroids without improvement. his hospitalization course was further complicated by acute renal failure, hyperbilirubinemia, metabolic encephalopathy, and ultimately acute respiratory failure requiring intubation and leading to his demise. figure 2. a) scanning photomicrograph of a biopsy from the left arm shows an ill-defined infiltrate of histiocytes and lymphocytes in the upper dermis (hematoxylin and eosin, 2x). b) higher power shows a non-caseating granuloma (hematoxylin and eosin, 20x). figure 3. bone marrow biopsy shows a non-caseating granuloma (hematoxylin and eosin, 20x) cvid is the most common primary immunodeficiency, with an annual incidence between 1:50,000 and 1:200,000. patients typically present with recurrent sinopulmonary infections, though clinical phenotype is highly variable. initial clinical manifestations are relatively nonspecific, often resulting in delayed diagnosis and treatment with subsequent increased risk of serious complications including chronic otitis media, deafness, pulmonary fibrosis, bronchiectasis, and cor pulmonale. cvid is also associated with autoimmune disorders and malignancy, with lymphoma being the most common cause of death, primarily of bcell origin and non-hodgkin type1. our patient was initially presumed to have sarcoidosis given the presence of noncaseating granulomas on skin pathology and prior bone marrow biopsy, in the context of new-onset cough and neurologic symptoms. granulomatous disease is observed in approximately 10% of cvid patients. of those cvid patients with granulomatous disease, the most commonly affected sites are lung (50%), lymph nodes (40%), and liver (30%). granulomatous discussion skin july 2019 volume 3 issue 4 copyright 2019 the national society for cutaneous medicine 256 involvement of the skin or bone marrow is less common, seen in approximately 20% and 5% of cvid patients, respectively2,3,4. cutaneous involvement in sarcoidosis is more common, with some reports citing up to 35% prevalence, whereas osseous bone involvement is seen in 10-15% of sarcoidosis patients5,6. cases of sarcoid involving the bone marrow have been reported, although very rare7,8. our patient’s neurological symptoms were initially attributed to neurosarcoidosis. though neurosarcoid-like granulomas in the setting of cvid have been reported9, this diagnosis was ruled out with normal findings on magnetic resonance imaging of brain and cerebrospinal fluid analysis. ultimately it was proposed that his progressive cognitive impairment may be explained by an underlying frontotemporal dementia leading to acute decompensation in mental status, secondary to recurrent infections and newly diagnosed lymphoma. sarcoidosis and cvid-associated granulomatous disease may be indistinguishable based on clinical and histological features2,10,11. the two entities, however, can be distinguished based upon immunoglobulin levels. low immunoglobulin (ig) levels are typical of cvid. a study of 224 cvid patients reported mean igg, iga, and igm levels at initial diagnosis as 258 mg/dl (reference range 768 to 1728 mg/dl), 28 mg/dl (reference range 99 to 396 mg/dl), and 40 mg/dl (reference range 38 to 266 mg/dl), respectively12. in contrast, sarcoidosis typically presents with polyclonal hypergammaglobulinemia10. finally, it is important to distinguish between the two clinical entities as the management highly differs. while sarcoidosis is typically steroid-responsive, cvid patients with granulomas are treated with ivig to address their primary immunodeficiency. treatment with ivig allows for an immunosuppressivesparing option in these patients with baseline immunosuppression, thus potentially avoid some of the complications seen in our patient. based on some case reports, treatment with ivig may improve the granulomas as well10. in some refractory cases, however, tnf-alpha inhibitors have been shown to improve the cvid-associated granulomas13. foot note: authors jeanette r. zambito and pooja r. shah contributed equally to this work. skin july 2019 volume 3 issue 4 copyright 2019 the national society for cutaneous medicine 257 conflict of interest disclosures: none. funding: none. corresponding author: jeanette r zambito university of rochester medical center, school of medicine and dentistry rochester, ny jeanette_zambito@urmc.rochester.edu references: 1. mortaz e, tabarsi p, mansouri d, et al. cancers related to immunodeficiencies: update and perspectives. front immunol. 2016;7:365. 2. ardeniz o, cunningham-rundles c. granulomatous disease in common variable immunodeficiency. clin immunol. 2009;133(2):198-207. 3. abdelhakim s, cafone j, basak rb. cutaneous manifestations of primary immunodeficiency. indian j paediatr dermatol 2017;18:155-9 4. salzer u, warnatz k, peter hh. common variable immunodeficiency: an update. arthritis res ther. 2012;14(5):223. 5. awada h, abi-karam g, fayad f. musculoskeletal and other extrapulmonary disorders in sarcoidosis. best pract res clin rheumatol. 2003;17:971–987 6. yanardag h, tetikkurt c, bilir m, demirci s, iscimen a. diagnosis of cutaneous sarcoidosis; clinical and the prognostic significance of skin lesions. multidiscip respir med. 2013;8(1):26. 7. sargın g, yavaşoğlu i, kadıköylü g, bolaman z. bone and bone marrow involvement in sarcoidosis. turk j haematol. 2014;31(2):192-3. 8. zhou y, lower ee, li h, farhey y, baughman rp. clinical characteristics of patients with bone sarcoidosis. semin arthritis rheum. 2017;47(1):143-148. 9. malhotra k, ramanathan s, agrawal d, rana s, scott t. neurology apr 2014, 82 (10 supplement) p5.171; 10. arnold df, wiggins j, cunninghamrundles c, misbah sa, chapel hm. granulomatous disease: distinguishing primary antibody disease from sarcoidosis. clin immunol. 2008;128(1):18-22. 11. roelandt pr, blockmans d. common variable immunodeficiency (cvid): case report and review of the literature. acta clin belg. 2009; 64:355-60 12. quinti i, soresina a, spadaro g, et al. long-term follow-up and outcome of a large cohort of patients with common variable immunodeficiency. j clin immunol. 2007;27(3):308-16. 13. smith kj, skelton h: common variable immunodeficiency treated with a recombinant human igg, tumour necrosis factor-alpha receptor. mailto:jeanette_zambito@urmc.rochester.edu mailto:jeanette_zambito@urmc.rochester.edu skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 233 in-depth review the implementation of educational videos in mohs micrographic surgery for improved patient satisfaction and comprehension: a review of literature antonio jimenez, bs1, kristyna gleghorn, md1, richard wagner, md1 1the university of texas medical branch, department of dermatology video education has become a popular, innovative tool to explain standardized health information to patients in a simple and interactive manner. it has demonstrated improved patient education and satisfaction in surgical and procedural specialties, including gynecologic surgery and plastic surgery.1 while verbal communication has long dominated patient education, there is encouraging evidence that instructional videos, which incorporate both verbal and visual learning techniques, are beneficial for patient education. mohs micrographic surgery (mms) is a surgical procedure that is performed by mohs surgeons for the removal of skin cancers. the surgery removes narrow, pathologic tissue margins until abstract background: patients are reported to understand less than half of the information communicated to them by physicians. in an effort to better promote patient education, instructional videos have been implemented in surgical specialties, with demonstrable improvement in patient satisfaction and knowledge. in mohs micrographic surgery (mms), mohs surgeons have begun to implement educational videos to supplement the traditional informed consent discussion and wound care demonstration. objective: to review published literature to determine if video education in mms can improve patient satisfaction and comprehension of their procedure. methods: a review of literature was performed using the pubmed database from 2000 to 2020. the articles selected focused on the implementation of educational videos in mohs surgery for improvement of the informed consent process, post-surgical wound care instructions, and overall patient satisfaction and comprehension. results: a total of seven articles met the criteria for review. the videos were noted to improve certain aspects of the informed consent discussion, including a patient’s knowledge on the procedural risks. in regard to wound care education, some patients preferred video education to surgeon instruction. while patient comprehension was similar between the intervention and control groups, most studies demonstrated overall patient satisfaction. in addition, the results noted that most patients who watched a video would recommend it to a peer undergoing mms. conclusion: educational videos have demonstrated promise for patient education in mms and patients are receptive to learn from them. introduction skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 234 histopathological tumor clearance is confirmed. it is performed for 3.5 million patients annually. a patient’s education on the procedure and their post-surgical expectations are important aspects of patient satisfaction, safety, and overall clinical outcomes. in mms, fleischman and garcia noted that patients who were informed of ten possible mohs-related complications had an overall retention rate of 24.4% after 1 week.2 the three most retained complications were death (45.9%), blood loss (41.2%), and scar formation (37.7%). while the patients were presented with the information in a straightforward manner and advised that their retention of the complications would be examined later, their recollection remained low. therefore, technological advancements in healthcare have sought to bridge this physician-patient communication gap with the integration of digital media (e.g., internet, e-mails, text messages, and videos) in medicine. while online information can provide patients with a quick and convenient source of mms knowledge, mohs surgeons are encouraged to utilize evidence-based patient education modalities – as internet resources available on the procedure are deemed too convoluted for patient comprehension.3 in an effort to improve patient participation and post-operative satisfaction, mohs surgeons have begun to implement creative techniques to better educate their patients, including the creation of their own educational videos that supplement the traditional informed consent and wound care discussions. the objective of this review is to determine if instructional videos are a suitable tool for patient education in mms. a review of published literature on mms and video education was performed on medline by pubmed from january 2020 to july 2020 for english-language articles. the following terms were searched: “mohs micrographic surgery” or “mohs surgery” combined with “videos,” “video education,” and “multimedia education.” the inclusion criteria were (1) the article was a randomized control trial and (2) the implementation of videos for patient education in mms was discussed. exclusion criteria were articles that did not discuss the implementation of videos to educate patients on mms. the pubmed search yielded twenty-two articles. of the twenty-two articles found, seven met the inclusion criteria and were reviewed. the reviewed articles assessed the usefulness of videos to address one of three important aspects of mms procedures: informed consent, post-surgical wound care instructions, and a patient’s perception of educational videos. each article’s research design, number of patients studied, and clinical endpoints are outlined in table 1. the impact of videos on informed consent in mms, the traditional informed consent conversation is limited to dialogue delivered by a mohs surgeon.4 a discussion about mms can become convoluted and leave patients overwhelmed and confused, which can diminish their overall clinical experience. in an effort to improve patient comprehension and satisfaction, three studies conducted research on the usefulness of educational videos to supplement the informed consent discussion in mms. west and colleagues created an instructional mms video to determine if it methods results skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 235 was a useful supplement to the informed consent process.5 patients were randomized into a video or non-video group. patients in both groups were then asked to complete a questionnaire regarding their satisfaction with the consent process. the results indicated that there were no significant differences in patient satisfaction between the two groups. however, the video group did report a moderate-to-significant improvement in understanding the procedure.5 there was also improvement in a patient’s perception on the ability to understand their procedure (p=0.038) and to ask questions (p=0.003). migden and his team created an educational video on the risks, benefits, and alternatives to mms.4 the video was delivered before the patients were asked to sign their consent form. patients were randomized into a video or non-video group. after the visit, both groups answered a satisfaction questionnaire on the consent process. all patients were satisfied with the consent process, regardless of the video; however, 100% of patients who watched the video method of informed consent would recommend it to a friend undergoing mms.4 delcambre et al created a video which highlighted the risks, benefits, and alternatives to mms. patients were randomized into an intervention and control group. after the informed consent process, the two groups were asked to complete a pre-operative state-trait anxiety inventory (stai), a 7-question satisfaction questionnaire, and 10 multiple-choice questions. in the video group, 82% of patients were satisfied with their preoperative education, compared to 66.7% of patients in the control group. however, the results were not of statistical significance (p=.212).6 there was also no significant difference in knowledge (p=.131) or anxiety levels (p=.626) between both groups. however, there was a significant difference (p <0.001) in a patient’s identification of procedural complications in the intervention group (88%) compared to the control (69%) based on their responses to the post-video questionnaire. after the video, three-fourths of subjects in the intervention group would recommend the informed consent video to other patients undergoing mms.6 the impact of videos on mms wound care instruction skin defects repaired during mms require aggressive wound care for prevention of post-surgical complications, including wound dehiscence, bleeding, or infection.7 traditional wound care instruction has relied on a conversation between the mohs surgeon/nurse and patient, with a stepwise, verbal description of a plan for action. however, the recent implementation of educational videos in select mohs practices has looked to audiovisual media to improve wound care instruction for their patients. two of the seven articles integrated educational videos before the traditional nurse demonstration to assess for improved wound care comprehension. migden et al created an educational video of a nurse demonstrating and discussing the proper application of a wound dressing. the video was shown to patients’ postprocedure, after which the nurse would enter the room and complete the traditional demonstration. the non-video group had a nurse demonstration and verbal instructions only. after the clinic visit, patients answered a satisfaction questionnaire and a multiplechoice quiz to evaluate their knowledge on the instruction provided.4 all patients were satisfied with their wound care instruction, and 100% of patients who watched the video would recommend it to a peer undergoing mms. in addition, the patients skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 236 who watched the video scored higher on average on their quiz (91.6% versus 84%).4 van acker’s team created a video in which a mohs surgeon discussed adequate wound care.7 the objective of the initiative was to evaluate a patient’s retention when a video was delivered preor post-mms, as the authors noted how traditional wound care conversations at the end of the visit were limited by post-surgical stress. after the completion of the video, the patients were asked to complete a 10-question multiplechoice quiz to assess their retention of wound care guidelines.7 the authors found no significant difference in overall questionnaire performance when the videos were delivered preor post-mms (77 士 14% versus 83 士 11%, p=0.13). however, 74% of the patients preferred the wound care video compared to a face-to-face demonstration with a healthcare provider.7 a patient’s perception of videos, anxiety, and overall satisfaction a patient’s receptiveness to learn from videos is important to consider, as their perception of the educational modality can determine its clinical value. hawkins and colleagues created an instructional video that described the mms procedure.8 three additional wound care videos were also created for patient-specific surgical repairs, including regular (flaps, primary closure), grafts, or extremity with compression wraps.8 patients were asked to complete a pre-video anxiety questionnaire and a 10-question procedural knowledge quiz; a satisfaction survey was also obtained at their 1-week follow-up visit. of the patients that watched the informational video (n=47), 94% of patients reported that the mms video was either “very helpful” or “helpful” in providing them with information about their procedure. 100% of patients who watched wound care video specific to their repair reported that it was “very helpful” or “helpful” in understanding how to provide adequate care for their wound.8 in regard to anxiety, patients in the video group had a mean anxiety level of 3.7/10 before their video. after the video, the average anxiety level was 3.0, which represented a 19% decrease (p=0.00062). there was no statistical significance between procedural knowledge in the video or non-video group (p=0.21498).8 in addition, 98% of patients agreed that videos should be used as a form of patient education.9 newsom and her team developed two informational videos on mms: a traditional, didactic video and a narrative video that included patient testimonials and procedural animations. before their consultation, patients were asked to answer the general anxiety disorder-7 (gad-7) to assess for pre-operative anxiety. all patients watched the video on initial intake and later met with the mohs surgeon. a post-video questionnaire was also given to assess a patient’s satisfaction. on a scale of 5, with 5 being the highest satisfaction level, the average scores were 4.7 and 4.6 between the narrative and traditional group, respectively. there was no significant difference in satisfaction levels between the two groups; however, both groups still demonstrated high satisfaction levels watching the consultation video, regardless of its traditional or narrative content. all established patients found the videos helpful but preferred the narrative (72.5%) over the traditional (27.5%) video (p=0.01).10 digital media is an emerging tool in mms, and it represents an effort to make patient education more accessible and discussion skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 237 table 1. patient video education in mohs surgery authors year study design article topic subjects (n) clinical end points results migden et al4 2008 randomized controlled trial informed consent, wound care 45 patients’ overall satisfaction and knowledge on mohs surgery after watching a video. 100% of patients in the video group would recommend it to a friend undergoing mms. patients who watched the video scored higher on their wound care instruction quiz (91.6% vs. 84%). van acker et al7 2014 randomized controlled trial wound care 51 patients’ knowledge on wound care if videos are delivered preor post-mohs surgery. no significant difference in overall questionnaire performance when the videos were delivered pre or post-mms (77 士 14% versus 83 士 11%, p=0.13). 74% of the patients preferred the wound care video compared to surgeon instruction. hawkins et al9 2017 investigatorblinded randomized controlled trial patient anxiety and satisfaction 90 patients’ perception of digital media for the delivery of health information in dermatologic surgery. 98% of patients reported that they would like other doctors to use educational videos as a form of patient education. newsom et al10 2018 randomized controlled trial patient anxiety and satisfaction 120 patients’ preference on mohsrelated video content. both the traditional and narrative video groups demonstrated high satisfaction levels watching the consultation video. hawkins et al8 2018 investigatorblinded randomized controlled trial patient anxiety and satisfaction 90 patients’ satisfaction, anxiety, and knowledge after watching a mms video. 94% of patients reported that the mms video was helpful. intervention group had a 19% decrease in anxiety after the video (p=0.00062). no statistical significance in procedural knoweldge was identified (p=0.21498). delcambre et al6 2020 single-center randomized controlled trial informed consent 231 patients’ satisfaction, anxiety, and comprehension after watching a mohs video. no significant difference in knowledge (p=0.131) or anxiety levels (p=0.626) was identified. a significant difference was noted in a patient's identification of procedural complications compared to the control (p<0.001). west et al5 2020 prospective, observational randomized control trial informed consent 60 patients’ satisfaction on mohs surgery after watching a video. no significant difference in patient comprehension between either group. intervention group demonstrated significance in their perception of greater opportunities to ask questions (p=0.003) and understand their procedure (p=.038). skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 238 comprehensible. instructional videos incorporate both verbal and visual cues to describe a select intervention. they can be interactive and engage patients more than traditional physician encounters. in order to gauge the value of videos as a tool for patient education in mms, mohs surgeons should consider their accessibility, a patient’s perception of digital media, and a patient’s receptiveness to learn from videos, as these aspects can determine long-term patient satisfaction and information retention. in published literature, educational videos have been used in mms to augment the traditional informed consent discussion and wound care demonstration. based on the results of the review, patients were receptive to learn from instructional videos on mms most of the studies demonstrated a positive trend of increased patient satisfaction and knowledge of procedural risks. in addition, patients in the video group were more likely to recommend video education to peers undergoing mms. while the studies were limited by their sample size, and there were only seven studies to review, the research on video education demonstrates that it could be useful to supplement traditional face-to-face conversations, such as in informed consent or wound care demonstrations. video education in mms has demonstrated promise and its content can be diverse and applicable to a range of mohs techniques. educational videos remain a challenging conundrum for healthcare providers. while most studies demonstrated improved patient satisfaction and comprehension after video education, it can be a difficult for mohs surgeons to create an instructional tool of clinical value, as patients have a diverse level of education, attention span, and learning style. it is important to consider the video’s content and length. delcambre and her team created a condensed 1:40 minute video on mms, but it was of insufficient duration to have a significant impact on patient knowledge.6 in contrast, newsom’s instructional video of 4-6 minutes addressed more patient concerns and questions, but 40% of participants reported that the video was “too long.”10 newsom and colleagues describe the challenge of creating a “onesize-fits-all” video, as patient preferences can range from a detailed illustration of the procedure to a real-life, beforeand aftermms photo comparison.10 in addition, mohs surgeries are patient-specific, and one broad video on mms might not be generalizable to their situation. hawkins et al thus created wound care videos that were specific to three common repairs in mms.8 the creation of a customizable, interactive video is therefore one potential option to address the range of patient procedures and learning techniques, as well as to incorporate active learning in the education process. nonetheless, the results of this review indicate that patients are appreciative and receptive of educational videos for mms education, regardless of their ability to address all of a patient’s individual concerns. based on this review, educational videos can be used to supplement the traditional face-to-face discussion. as per migden’s article, patients who watched mms videos asked more subjectively educated questions in comparison to patients who did not.4 the videos thus can lead to effective, yet succinct conversations with patients. mohs surgeons should consider the creation and integration of instructional videos for their current practice, as the evidence trends toward increased patient satisfaction and comprehension of procedural risks. skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 239 public health is interdependent on patient education. technological innovations such as high-definition video modules have demonstrated effectiveness in bridging the physician-patient communication gap in other specialties. mms is a complex surgical procedure that necessitates patient comprehension for informed consent and adequate post-surgical wound care instruction. the implementation of educational videos for mms has demonstrated promise. the results of this review indicate that multimedia has the potential to be as effective as physician instruction – and is sometimes even preferred. in addition, some articles noted how video education increased a patient’s recognition of mms risks and benefits. while more research needs to be done on the utilization and effectiveness of videos for mms education, this review highlights the widespread patient acceptance of instructional videos for patient care and health education. conflict of interest disclosures: none funding: none corresponding author: antonio jimenez, bs 301 university blvd galveston, tx 75555 phone: 956-763-5779 email: anrjimen@utmb.edu references: 1. koya kd, bhatia kr, hsu jt, bhatia ac. youtube and the expanding role of videos in dermatologic surgery education. semin cutan med surg. 2012;31(3):163-167. 2. fleischman m, garcia c. informed consent in dermatologic surgery. dermatol surg. 2003;29(9):952-955. 3. vargas cr, depry j, lee bt, bordeaux js. the readability of online patient information about mohs micrographic surgery. dermatol surg. 2016;42(10):1135-1141. 4. migden m, chavez-frazier a, nguyen t. the use of high definition video modules for delivery of informed consent and wound care education in the mohs surgery unit. semin cutan med surg. 2008;27(1):89-93. 5. west l, srivastava d, goldberg lh, nijhawan ri. multimedia technology used to supplement patient consent for mohs micrographic surgery. dermatol surg. 2020;46(5):586-590. 6. delcambre m, haynes d, hajar t, et al. using a multimedia tool for informed consent in mohs surgery: a randomized trial measuring effects on patient anxiety, knowledge, and satisfaction. dermatol surg. 2020;46(5):591-598. 7. van acker mm, kuriata ma. video education provides effective wound care instruction preor post-mohs micrographic surgery. j clin aesthet dermatol. 2014;7(4):43-47. 8. hawkins sd, koch sb, williford pm, feldman sr, pearce dj. web appand text messagebased patient education in mohs micrographic surgery-a randomized controlled trial. dermatol surg. 2018;44(7):924-932. 9. hawkins sd, barilla s, williford pwm, feldman sr, pearce dj. patient perceptions of textmessages, email, and video in dermatologic surgery patients. dermatol online j. 2017;23(4):1-3. 10. newsom e, lee e, rossi a, dusza s, nehal k. modernizing the mohs surgery consultation: instituting a video module for improved patient education and satisfaction. dermatol surg. 2018;44(6):778-784. conclusion efficacy of ala–pdt in the treatment of actinic keratoses on the upper extremities: a post hoc analysis of a phase 3, randomized, vehicle-controlled trial brian berman,1,2 neal bhatia,3 daniel piacquadio,4 anna houlihan,5 and daniel siegel6,7 1center for clinical and cosmetic research, aventura, fl, usa; 2department of dermatology and cutaneous surgery, university of miami miller school of medicine, miami, fl, usa; 3therapeutics clinical research, san diego, ca, usa; 4therapeutics, inc., san diego, ca, usa; 5dusa pharmaceuticals, inc., wilmington, ma, usa; 6department of dermatology, the state university of new york downstate health sciences university, brooklyn, ny, usa; 7dermatology service, veterans affairs new york harbor healthcare system, brooklyn, ny, usa background • actinic keratoses (aks) are precancerous, dysplastic epidermal lesions that may progress to squamous cell carcinoma (scc)1 • aminolevulinic acid (ala) 20% solution photodynamic therapy (pdt) is indicated for targeted treatment of ak on the face, scalp, and upper extremities2 • in a phase 3, randomized, evaluator-blinded, vehicle-controlled trial (nct02137785), ala 20% solution–pdt at baseline and week 8 using lesion-targeted treatment and a 3-hour occluded incubation was superior to vehicle (veh)–pdt for ak clearance of the upper extremities3 — the study assessed response of the entire field to treatment, including new aks present at follow-up, in calculations of clearance rates objective • to assess clearance rate relative to baseline, cumulative disease area clearance, and complete clearance rate by lesion size in treated lesions only in patients treated with ala-pdt for aks on the upper extremities methods study design • this is a post hoc analysis of a phase 3, randomized, evaluator-blinded, vehicle-controlled, parallel group trial (nct02137785) conducted between may 8, 2014, and march 5, 20153 • the study enrolled men and women ≥18 years of age with 4–15 grade 1–2 aks on ≥1 upper extremity treatment area, defined as the area between the elbow and the base of the fingers • if both arms qualified for inclusion, the treatment arm was defined as the arm with greater number of lesions, or the arm with higher grade lesions if both had an equal number • major exclusion criteria included presence within the treatment area of grade 3 or atypical aks larger than 1 cm, lesions suspicious for skin cancer, or untreated skin cancer • patients were randomized in a 1:1 ratio to receive topical application of ala 20% or veh to aks within the treatment area, followed by 3 h incubation with occlusion and 10 j/cm2 blue light photodynamic therapy at 10 mw/cm2 • treatment was repeated at week 8 if any lesions were present within the treatment area, and patients were followed for up to 12 weeks postbaseline endpoints and assessments • ak lesion count and mapping were performed at baseline and at weeks 4, 8, and 12; lesion size and grade were assessed at baseline and at weeks 8 and 12 • post hoc assessments included mean ak clearance rate compared to baseline, cumulative disease area clearance, and subgroup analysis of complete clearance rate by lesion size • safety assessments included assessment of pdt responses (tolerability) and adverse event (ae) monitoring throughout the study statistical analyses • continuous variables were summarized using descriptive statistics (n, mean, median, standard deviation [sd], and range), and categorical variables were summarized using frequency counts and percentages • lesion clearance rate was calculated as (1 – number of treated ak lesions present at follow-up/ number of ak lesions at baseline) x 100 • percent cumulative disease area cleared was calculated as (1 – sum of treated lesion sizes at follow-up/sum of lesion sizes at baseline) x 100 • statistical comparisons of clearance rate and percent cumulative disease area cleared used a linear mixed model with fixed effects for treatment group, time point, and treatment group by time point interaction results • the study enrolled 269 patients,135 and 134 randomized to ala-pdt and veh-pdt, respectively; 132 (97.8%) patients who received ala-pdt and 130 (97.0%) patients who received veh-pdt treatment completed the study, and all patients were included in the current post hoc analysis • the mean (sd) age was 67.6 (8.6) and 67.6 (9.4) years for the ala-pdt and vehicle group respectively; patients were predominantly male (188 [69.9%]) both in the ala-pdt (92 [68.1%]) and the veh-pdt group (96 [71.6%], table 1) • the mean (sd) number of lesions per patient in the treated area at baseline was 8.5 (3.6) for the ala-pdt group and 8.6 (3.4) for the veh-pdt group (table 1) • the mean cumulative disease area at baseline was 149 mm2 and 154 mm2 for ala-pdt and vehpdt-treated aks, respectively (table 1) table 1. patient demographics and baseline disease characteristics ala-pdt (n = 135) veh-pdt (n = 134) age, years, mean (sd) 67.6 (8.6) 67.6 (9.4) sex, male 92 (68.1) 96 (71.6) ethnicity hispanic or latino 0 3 (2.2) not hispanic or latino 135 (100.0) 131 (97.8) race white 135 (100.0) 134 (100.0) number of lesions 1150 1149 grade 1 576 (50.1) 580 (50.5) grade 2 574 (49.9) 569 (49.5) lesions per patient, mean (sd) 8.5 (3.6) 8.6 (3.4) mean cumulative disease area, mm2 149 154 data presented as n (%) unless otherwise indicated. ala-pdt, aminolevulinic acid combined with photodynamic therapy; sd, standard deviation; veh-pdt, vehicle combined with photodynamic therapy. • the mean (sd) ak clearance rate for lesions of all sizes treated with ala-pdt was 80.6% (22.6%) at 12 weeks (after up to 2 treatments), compared with 45.5% (37.2%) for lesions treated with vehpdt (p <0.0001, linear mixed model, figure 1) figure 1. clearance rate of treated actinic keratoses of all sizes at week 8 and 12 ***p <0.0001 using linear mixed model with fixed effects for treatment group, time point, and treatment group by time point interaction. ak, actinic keratosis; ala-pdt, aminolevulinic acid combined with photodynamic therapy; sd, standard deviation; veh-pdt, vehicle combined with photodynamic therapy. • at week 12, a mean (sd) of 82.4% (26.3%) of the cumulative disease area was cleared after alapdt, compared with 42.6% (49.4%) after veh-pdt (p <0.0001, linear mixed model, figure 2) figure 2. percent cumulative disease area cleared at week 8 and 12 ***p <0.0001 using linear mixed model with fixed effects for treatment group, time point, and treatment group by time point interaction. ala-pdt, aminolevulinic acid combined with photodynamic therapy; sd, standard deviation; veh-pdt, vehicle combined with photodynamic therapy. • more than half of patients treated with ala-pdt experienced complete clearance of larger lesions at 12 weeks, with 48/68 (70.6%) patients exhibiting complete clearance of lesions 25–36 mm2 and 25/42 (59.5%) patients exhibiting complete clearance of lesions ≥36 mm2 (table 2) table 2. clearance of lesions by size at week 8 and 12 week 8 week 12 bl lesion size n complete clearance ≥75% clearance n complete clearance ≥75% clearance <10 mm2 ala-pdt 95 44 (46.3) 59 (62.1) 104 59 (56.7) 74 (71.2) veh-pdt 90 15 (16.7) 23 (25.6) 104 25 (24.0) 37 (35.6) 10–25 mm2 ala-pdt 103 43 (41.7) 49 (47.6) 115 66 (57.4) 72 (62.6) veh-pdt 102 20 (19.6) 24 (23.5) 114 31 (27.2) 38 (33.3) 25–36 mm2 ala-pdt 57 32 (56.1) 33 (57.9) 68 48 (70.6) 50 (73.5) veh-pdt 52 18 (34.6) 18 (34.6) 56 18 (32.1) 18 (32.1) ≥36 mm2 ala-pdt 37 20 (54.1) 22 (59.5) 42 25 (59.5) 31 (73.8) veh-pdt 40 9 (22.5) 9 (22.5) 43 11 (25.6) 13 (30.2) data presented as n (%) unless otherwise indicated. ala-pdt, aminolevulinic acid combined with photodynamic therapy; bl, baseline; veh-pdt, vehicle combined with photodynamic therapy. presented at fall clinical dermatology conference for pas & nps 2020, april 3–5, orlando, fl, usa • reactions to pdt were all expected, nonserious, and would typically resolve within several weeks • as anticipated, pretreatment with ala resulted in a greater incidence and severity of certain pdt side effects (erythema, edema, stinging/burning, scaling and dryness, and oozing/vesiculation/ crusting) than was seen after pretreatment with veh • by the end of the study (4 weeks after the second pdt treatment), most patients had returned to their baseline status with respect to these effects • no clinically significant aes were reported for either study group (table 3) and there were no discontinuations due to aes • a total of 16 skin carcinomas were diagnosed in the study: — nine sccs were diagnosed in 7 patients treated with ala-pdt, all of whom had prior history of scc; 2 sccs were within the treatment area — three sccs were diagnosed in 3 patients treated with veh-pdt, of whom 2 had prior history of scc; 1 scc was within the treatment area — four bccs were diagnosed in 3 patients treated with veh-pdt, all of whom had prior history of bcc; no bccs were within the treatment area table 3. adverse events reported in ≥3 patients in either treatment group ala-pdt (n = 135) veh-pdt (n = 134) infections and infestations nasopharyngitis 2 (1.5) 4 (3.0) sinusitis 3 (2.2) 0 neoplasms benign, malignant, and unspecified (including cysts and polyps) basal cell carcinoma 0 3 (2.2) squamous cell carcinoma 3 (2.2) 1 (0.7) squamous cell carcinoma of skin 4 (3.0) 2 (1.5) data presented as n (%). ala-pdt, aminolevulinic acid combined with photodynamic therapy; veh-pdt, vehicle combined with photodynamic therapy. conclusions • ala-pdt resulted in significantly higher clearance rates of treated aks and significantly higher percent of treated disease area cleared vs veh-pdt, with good response of large lesions • therapy with ala-pdt was well tolerated, and no safety concerns were raised references 1. criscione, vd et al. cancer. 2009; 115:2523–30. 2. levulan kerastick (aminolevulinic acid hcl) for topical solution, 20%. full prescribing information. dusa pharmaceuticals, inc., wilmington, ma, usa. 2017. 3. brian jiang, si et al. dermatol surg. 2019; 45:890–7. acknowledgments we thank the patients for their participation. the study was supported by dusa pharmaceuticals, inc. medical writing support was provided by ginny feltzin, phd, of alphabiocom, llc, and was funded by sun pharmaceutical industries, inc. disclosures bb has received grants and consulting fees from anacor; pfizer; dusa pharmaceuticals, inc., sun pharmaceutical industries, inc.; and biofrontera. nb is an advisor, consultant, investigator, and speaker for anacor, merz, sandoz, and valeant. dp is an employee of therapeutics inc. ah is an employee of dusa pharmaceuticals, inc. ds is a member of the board of directors for caliber i.d.; member of the clinical advisory board for michelson diagnostics, ltd; and an advisory board attendee for castle biosciences inc. week 8 week 12 37.2 45.5 67.3 80.6 *** *** ala-pdt veh-pdt 0 20 40 60 80 100 m ea n c le ar an ce ra te o f tr ea te d a k s + s d ala-pdt veh-pdt 37.2 42.6 67.8 82.4 *** *** week 8 week 12 0 20 40 60 80 100 p er ce n t c u m u la ti ve d is ea se ar ea c le ar ed + s d efficacy outcomes in the phase 3 combi-ad study of adjuvant dabrafenib plus trametinib vs placebo in patients with stage iii braf v600e/k–mutant melanoma georgina v. long,1 axel hauschild,2 mario santinami,3 victoria atkinson,4 mario mandalà,5 vanna chiarion-sileni,6 james larkin,7 marta nyakas,8 caroline dutriaux,9 andrew haydon,10 caroline robert,11 laurent mortier,12 jacob schachter,13 dirk schadendorf,14 thierry lesimple,15 ruth plummer,16 ran ji,17 pingkuan zhang,17 bijoyesh mookerjee,17 jeff legos,17 richard kefford,18 reinhard dummer,19 john m. kirkwood20 1melanoma institute australia, the university of sydney, royal north shore and mater hospitals, sydney, nsw, australia; 2university hospital schleswig-holstein, kiel, germany; 3fondazione istituto nazionale tumori, milano, italy; 4princess alexandra hospital, gallipoli medical research foundation, university of queensland, qld, australia; 5papa giovanni xxiii cancer center hospital, bergamo, italy; 6melanoma oncology unit, veneto oncology institute, gattamelata, padova, italy; 7royal marsden nhs foundation trust, london, united kingdom; 8oslo university hospital, oslo, norway; 9centre hospitalier universitaire de bordeaux, hôpital saintandré, bordeaux, france; 10the alfred hospital, melbourne, vic, australia; 11institute gustave roussy, paris, france; 12université de lille, inserm u 1189, chru lille, france; 13ella institute for melanoma, sheba medical center, tel hashomer, israel; 14university hospital essen, essen, germany, and german cancer consortium, heidelberg, germany; 15medical oncology department, centre eugène marquis, rennes, france; 16northern centre for cancer care, freeman hospital, newcastle upon tyne, united kingdom; 17novartis pharmaceuticals corporation, east hanover, nj, united states; 18macquarie university, melanoma institute australia, westmead hospital, and university of sydney, nsw, australia; 19university hospital zürich skin cancer center, zürich, switzerland; 20melanoma program, hillman upmc cancer center, university of pittsburgh, pittsburgh, pa, united states introduction • surgery alone is often curative for patients with localized melanoma; however, those with regional involvement (stage iii disease) are at a higher risk for disease progression even with complete surgical resection.1,2 • in phase 3 trials involving patients with previously untreated advanced or metastatic braf v600-mutant melanoma, dabrafenib plus trametinib combination therapy improved clinical outcomes and was well tolerated.3,4 • the combi‑ad study (nct01682083) is a randomized, double-blind, placebo-controlled, phase 3 trial that evaluated the efficacy and safety of dabrafenib plus trametinib combination therapy in patients with completely resected, high-risk, stage iii, braf v600e/k-mutant melanoma without prior anticancer therapy.5 figure 1. study rationale3, 5–8 time from randomisation, months o s , p ro p o rt io n a liv e 0 6 12 18 24 30 36 42 1.0 0.0 0.8 0.6 0.4 0.2 48 54 60 66 dabrafenib dacarbazine dabrafenib plus trametinib dabrafenib plus placebo perk proliferation, survival, invasion, metastasis ras mek mut braf dabrafenib mapk pathway trametinib overall survival benefit in braf v600–mutant stage iv melanoma can we prevent stage iv? mapk, mitogen-activated protein kinase; mut, mutated; perk, phosphorylated extracellular signalregulated kinase. figure 2. study design 1:1 dabrafenib 150 mg bid + trametinib 2 mg qd (n = 438) 2 matched placebos (n = 432) n = 870 follow-upb until end of studyc median follow-up for primary analysis: 2.8 years • primary endpoint: rfsd • secondary endpoints: os,e dmfs, ffr, safety treatment duration: 12 monthsa r a n d o m i s a t i o n key eligibility criteria • completely resected stage iiia (lymph node metastasis > 1 mm), iiib, or iiic cutaneous melanoma • braf v600e/k mutation • surgically free of disease ≤ 12 weeks before randomisation • ecog performance status 0 or 1 • no prior radiotherapy or systemic therapy stratification • braf mutation status (v600e, v600k) • disease stage (iiia, iiib, iiic) bid, twice daily; dmfs, distant metastasis–free survival; ecog, eastern cooperative oncology group; ffr, freedom from relapse; os, overall survival; qd, once daily; rfs, relapse-free survival. a or until disease recurrence, death, unacceptable toxicity, or withdrawal of consent. b patients were followed for disease recurrence until the first recurrence and thereafter for survival. c the study will be considered complete and final os analysis will occur when ≈ 70% of randomized patients have died or are lost to follow-up. d study was designed to provide > 90% power (assuming ≈ 410 rfs events observed) to detect an hr of 0.71 with an overall 2-sided type i error rate of 5%. new primary melanoma considered as an event. e os was to be tested only if the primary endpoint (rfs) significantly favoured the combination arm. figure 3. primary analysis: rfs and os median follow-up: 2.8 years 438 413 405 392 382 373 355 336 325 299 282 276 263 257 233 202 194 147 116 110 66 52 42 19 7 2 0 432 387 322 280 263 243 219 203 198 185 178 175 168 166 158 141 138 106 87 86 50 33 30 9 3 0 0 no. at risk 0 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 p ro p o rt io n a liv e a n d r e la p se f re e 1 y, 88% 2 y, 67% 3 y, 58%1 y, 56% 2 y, 44% 3 y, 39% relapse-free survival (primary endpoint) overall survival months from randomisation group events, n (%) median (95% ci), months hr (95% ci) dabrafenib plus trametinib 166 (38) placebo 248 (57) nr (44.5-nr) 16.6 (12.7-22.1) 0.47 (0.39-0.58); p <.001 1 y, 97% 2 y, 91% 3 y, 86% 1 y, 94% 2 y, 83% 3 y, 77% 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 p ro p o rt io n a liv e group events, n (%) median (95% ci), months hr (95% ci) dabrafenib plus trametinib 60 (14) placebo 93 (22) nr (nr-nr) nr (nr-nr) 0.57 (0.42-0.79); p = .0006a 438 426 432 425 0 2 416 415 4 414 410 6 408 401 8 401 386 10 395 378 12 387 362 14 381 346 16 376 337 18 370 328 20 366 323 22 362 308 24 352 303 26 328 284 28 301 269 30 291 252 32 233 202 34 180 164 36 164 152 38 105 94 40 82 64 42 67 51 44 28 17 46 12 7 48 5 1 50 0 0 52 0 0 54 no. at risk months from randomisation data cutoff: 30 june 2017. nr, not reached. a prespecified significance boundary (p = .000019); next interim analysis planned when 50% of events have occurred. figure 4. primary analysis: rfs by subgroup 0.01 1.000.10 0.51 0.37 0.51 0.33 0.43 0.43 10.00hazard ratio favours dabrafenib plus trametinib 0.45 0.50 0.38 0.51 0.55 0.43 0.48 0.54v600k (n = 78) v600e (n = 792) male (n = 482) female (n = 388) < 65 years (n = 712) ≥ 65 years (n = 158) disease stage iiia (n = 154) disease stage iiib (n = 356) disease stage iiic (n = 347) micrometastasis(n = 309) macrometastasis(n = 319) micrometastasis and ulceration (n = 143) micrometastasis and no ulceration (n = 165) macrometastasis and ulceration (n = 116) macrometastasis and no ulceration (n = 201) 1 nodal metastatic mass (n = 360) 2–3 nodal metastatic masses (n = 308) ≥ 4 nodal metastatic masses (n = 145) 0.52 0.49 0.44 0.44 favours placebo data cutoff: 30 june 2017. figure 5. rfs: stage iiia 83 81 81 80 79 77 76 74 73 70 68 66 62 62 58 52 51 40 34 33 12 6 5 3 0 0 71 67 59 56 55 53 50 46 45 44 43 42 41 41 39 34 32 22 20 20 6 4 4 0 0 0 months from randomisation dabrafenib plus trametinib placebo no. at risk 0 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 p ro p o rt io n a liv e a n d r e la p se f re e 2 y, 84.3% 3 y, 79.3%1 y, 79.3% 1 y, 97.5% 2 y, 69.5% 3 y, 62.9% group events, n (%) hr (95% ci) dabrafenib plus trametinib 15 (18) nr (nr-nr) nr (nr-nr) 0.44 (0.23-0.84)placebo 23 (32) median (95% ci), months nr, not reached. figure 6. rfs: stage iiib 169 161 158 151 147 142 134 126 121 110 103 101 99 96 84 72 70 50 40 38 32 25 21 10 4 2 187 177 154 135 126 116 102 95 92 84 79 79 74 73 67 57 57 49 38 38 27 19 18 7 2 0 dabrafenib plus trametinib placebo no. at risk 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 1 y, 87.2% 2 y, 65.6% 3 y, 57.3%1 y, 58.8% 2 y, 43.7% 3 y, 38.5% 0 0 52 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 p ro p o rt io n a liv e a n d r e la p se f re e group events, n (%) hr (95% ci) dabrafenib plus trametinib 64 (38) nr (33.2-nr) 17.2 (13.8-27.5) 0.50 (0.37-0.67)placebo 110 (59) median (95% ci), months months from randomisation nr, not reached. figure 7. rfs: stage iiic 181 167 162 157 152 150 142 133 128 116 109 107 100 97 89 76 71 56 41 38 21 20 16 6 3 0 166 137 103 84 77 69 64 59 58 54 53 51 50 49 49 47 46 33 27 26 15 9 7 2 1 0 dabrafenib plus trametinib placebo no. at risk 0 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 p ro p o rt io n a liv e a n d r e la p se f re e months from randomisation 1 y, 85.6% 2 y, 60.9% 3 y, 50.2% 1 y, 42.2% 2 y, 34.2% 3 y, 30.0% 0 0 52 group events, n (%) hr (95% ci) dabrafenib plus trametinib 84 (46) 39.5 (27.4-nr) 7.4 (5.6-11.5) 0.45 (0.33-0.60)placebo 111 (67) median (95% ci), months nr, not reached. figure 8. rfs: stage iiib and iiic 350 328 320 308 299 292 276 259 249 226 212 208 199 193 173 148 141 106 81 76 53 45 37 16 7 2 353 314 257 219 203 185 166 154 150 138 132 130 124 122 116 104 103 82 65 64 42 28 25 9 3 0 dabrafenib plus trametinib placebo no. at risk 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 0 0 52 1 y, 86% 2 y, 63% 3 y, 54% 1 y, 51% 2 y, 39% 3 y, 35% 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 p ro p o rt io n a liv e a n d r e la p se f re e months from randomisation group events, n (%) hr (95% ci) dabrafenib plus trametinib 148 (42) 44.5 (33.1-nr) 12.8 (9.5-16.9) 0.48 (0.39-0.59)placebo 221 (63) median (95% ci), months nr, not reached. figure 9. rfs: micrometastases 152 144 143 138 136 133 129 123 122 114 110 107 102 102 96 85 82 60 51 50 24 14 12 5 1 1 157 149 134 121 116 109 99 92 89 84 80 79 75 75 69 60 58 45 36 36 17 12 12 3 2 0 dabrafenib plus trametinib placebo no. at risk 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 0 0 52 1 y, 93.6% 2 y, 77.4% 3 y, 70.3%1 y, 70.0% 2 y, 55.6% 3 y, 49.5% 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 p ro p o rt io n a liv e a n d r e la p se f re e months from randomisation group events, n (%) hr (95% ci) dabrafenib plus trametinib 39 (26) nr (nr-nr) 33.1 (19.8-nr) 0.44 (0.30-0.64)placebo 72 (46) median (95% ci), months nr, not reached. figure 10. rfs: macrometastases 158 150 147 142 138 135 128 120 115 107 99 97 96 92 79 67 63 48 35 32 26 23 18 8 2 0 161 148 122 102 93 85 75 68 67 61 59 57 55 54 52 46 45 37 32 31 23 14 12 5 0 0 dabrafenib plus trametinib placebo no. at risk 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 0 0 52 1 y, 87.2% 2 y, 66.7% 3 y, 58.1% 1 y, 51.4% 2 y, 38.2% 3 y, 35.4% 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 p ro p o rt io n a liv e a n d r e la p se f re e months from randomisation group events, n (%) hr (95% ci) dabrafenib plus trametinib 61 (39) nr (33.1-nr) 13.6 (8.3-19.2) 0.43 (0.31-0.58)placebo 101 (63) median (95% ci), months nr, not reached. figure 11. rfs: without primary tumour ulceration 253 243 240 234 228 222 215 207 201 184 175 172 162 157 141 120 119 95 76 72 40 30 24 12 2 0 249 230 192 172 161 152 137 128 126 120 116 115 111 109 104 90 88 64 53 53 30 21 20 5 0 0 dabrafenib plus trametinib placebo no. at risk 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 0 0 52 1 y, 90.8% 2 y, 70.3% 3 y, 63.3% 1 y, 59.8% 2 y, 50.4% 3 y, 44.2% 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 p ro p o rt io n a liv e a n d r e la p se f re e months from randomisation group events, n (%) hr (95% ci) dabrafenib plus trametinib 87 (34) nr (45.6-nr) 24.4 (15.9-41.2) 0.49 (0.37-0.64)placebo 130 (52) median (95% ci), months nr, not reached. figure12. rfs: with primary tumour ulceration 179 165 160 153 150 148 138 127 122 113 106 103 100 99 91 81 74 52 40 38 26 22 18 7 5 2 177 153 127 105 99 88 80 73 70 63 60 58 55 55 52 49 48 40 32 31 18 12 10 4 3 0 dabrafenib plus trametinib placebo no. at risk 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 0 0 52 1 y, 85.4% 2 y, 63.0% 3 y, 52.2% 1 y, 50.2% 2 y, 35.7% 3 y, 32.3% 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 p ro p o rt io n a liv e a n d r e la p se f re e group events, n (%) hr (95% ci) dabrafenib plus trametinib 76 (42) 44.5 (29.3-nr) 12.0 (8.3-16.6) 0.46 (0.34-0.61)placebo 114 (64) months from randomisation median (95% ci), months nr, not reached. table 1. type of recurrence at first recurrence type of recurrence, n (%) dabrafenib plus trametinib (n = 166) placebo (n = 248) distant recurrence 103 (62) 133 (54) local/regional recurrence 61 (37) 114 (46) secondary primary melanoma 7 (4) 8 (3) death 3 (2) 1 (< 1) table 2. primary analysis: safety summary ae category, n (%) dabrafenib plus trametinib (n = 435) placebo (n = 432) any ae 422 (97) 380 (88) aes related to study treatment 398 (91) 272 (63) grade 3/4 aes related to study treatment 136 (31) 21 (5) any sae 155 (36) 44 (10) saes related to study treatment 117 (27) 17 (4) aes leading to dose interruption 289 (66) 65 (15) aes leading to dose reduction 167 (38) 11 (3) aes leading to treatment discontinuationa 114 (26) 12 (3) fatal aes related to study drug 0 0 ae, adverse event; sae, serious adverse event. a most common aes leading to treatment discontinuation in the dabrafenib plus trametinib arm were pyrexia (9%) and chills (4%). • most common aes in the dabrafenib plus trametinib arm were pyrexia (63%) and fatigue (47%) table 3. characterisation of pyrexia events dabrafenib plus trametinib (n = 435) placebo (n = 432) patients with pyrexia events, n (%) 292 (67) 66 (15) median time to onset of first pyrexia occurrence (range), days 23 (1-28) 53 (1-373) median duration of pyrexia (range), days 3 (1-92) 3 (1-340) pyrexia event characteristics, n (%)a serious adverse event grade 3 grade 4 71 (24) 24 (8) 1 (< 1) 4 (6) 2 (3) 0 number of pyrexia occurrences, n (%)a 1 2 ≥ 3 83 (28) 57 (20) 152 (52) 45 (68) 11 (17) 10 (15) a percentage based on number of patients with pyrexia. table 4. pyrexia management and outcome dabrafenib plus trametinib (n = 435) placebo (n = 432) action taken with dabrafenib/trametinib, n (%)a drug withdrawn dose reduced drug interrupted 40 (14)/27 (9) 86 (29)/18 (6) 202 (69)/121 (41) — — — recovered/resolved, n (%)a 289 (99) 64 (97) a percentage based on number of patients with pyrexia. table 5. secondary malignanciesa dabrafenib plus trametinib (n = 435) placebo (n = 432) new primary melanoma 11 (3) 10 (2) new cuscc or keratoacanthoma 8 (2) 7 (2) new basal cell carcinoma 19 (4) 14 (3) new nonskin malignancies 10 (2) • endometrial, n = 2 • lung, breast, renal cell, adenocarcinoma nos, chronic myeloid leukaemia, b-cell lymphoma, lymphoma, prostate, n = 1 each 4 (1) • colon, pancreatic, renal cell, bladder transitional cell, n = 1 each cuscc, cutaneous squamous cell carcinoma; nos, not otherwise specified. a includes events occurring after randomisation. data presented as: n (%). conclusions • dabrafenib plus trametinib reduced the risk of disease recurrence vs placebo in patients with resected stage iii, braf v600e/k–mutant melanoma; this result was statistically significant and clinically meaningful – rfs hr, 0.47 (95% ci, 0.39-0.58; p < .001) – os hr, 0.57 (95% ci, 0.42-0.79, p = .0006 [prespecified significance boundary, p = .000019]) • rfs benefit was observed in all patient subgroups – stage iiia hr, 0.44; stage iiib hr, 0.50; stage iiic hr, 0.45 – micrometastases hr, 0.44; macrometastases hr, 0.43 – nonulcerated hr, 0.49; ulcerated hr, 0.46 • although pyrexia was the most common ae, it was well characterised and manageable • dabrafenib plus trametinib represents a significant advance for the adjuvant treatment of stage iii braf v600–mutant melanoma acknowledgements • we thank the patients and their families for their participation • we also thank study site staff, additional investigators, and others for their contributions • this study was sponsored by glaxosmithkline; dabrafenib and trametinib are assets of novartis ag as of 2 march 2015 • financial support for medical editorial assistance was provided by novartis pharmaceuticals corporation references 1. gershenwald je, et al. ca cancer j clin. 2017;67(6):472-492. 2. siegel rl, et al. ca cancer j clin. 2017;67(1):7-30. 3. long gv, et al. ann oncol. 2017;28(7):1631-1639. 4. robert c, et al. n engl j med. 2015;372(1):30-39. 5. long gv, et al. n engl j med. 2017;377(19):1813-1823. 6. long gv, et al. j clin oncol. 2011;29:1239-1246. 7. jakob ja, et al. cancer. 2012;118:4014-4023. 8. chapman pb, et al. j clin oncol. 2017;35:[abstract 9526]. poster presentation at the winter clinical dermatology conference; january 12–17, 2018; kaanapali, hi. this was previously presented at the 9th world congress of melanoma/14th international congress of the society for melanoma research skin january 2019 volume 3 issue 1 copyright 2018 the national society for cutaneous medicine 47 compelling comments was it auspitz’s sign? andrew m armenta, bs1, alex steele, bs2, mara m dacso, md3 1university of texas medical branch school of medicine, galveston, tx 2university of texas health and science center at san antonio, san antonio, texas 3department of dermatology, university of texas southwestern medical center, dallas, texas the auspitz sign describes the phenomenon of pinpoint bleeding following the scraping of psoriatic plaques’ silvery scale – a classic finding in psoriasis. this finding is due to both a thinning of the epidermis and exposure of the underlying dilated post-capillary venules located within the dermal papillae. although first described in psoriasis, this clinical feature can be demonstrated in other skin conditions like darier’s disease and actinic keratosis.1 today, most associate this psoriatic pinpoint bleeding with carl heinrich auspitz, an austrian dermatologist. however, contrary to what the eponym suggests, auspitz was not the first to describe the phenomenom.2,3 the earliest known description of this finding was written by daniel turner, a disfranchised surgeon who, in 1736, wrote, “in [a patient],…whose knee a large [lichen] eruption, was seated, accompanied with great itching: whence, upon rubbing, a scale should throw off…i raised one of these…with the edge of my spathula, several small specks of blood appeared underneath…”.2 again in 1808 while commenting on psoriasis, english dermatologist robert willan, wrote, “...should any portion of the diseased surface be forcibly excoriated, there issues out a thin lymph, mixed with some drops of blood”.2 30 years later, auspitz’s mentor, ferdinand ritter von hebra, was credited for first observing this clinical sign in one of moritz kaposi’s textbooks, without mention of auspitz.2 how then did the name of carl heinrich auspitz become tacked to this quickly recognizable finding? the auspitz sign is known as it is today not because of his discovery, but rather his impactful treatise on pathology and therapeutics of the skin.3 it is in this treatise he describes the phenomenon that has been attributed to his name.3 it was translated into english in 1885 and became one of the early foundational pieces of modern european dermatopathology. conflict of interest disclosures: none. funding: none. corresponding author: mara m. dacso, m.d. university of texas southwestern medical center, dallas, texas mara.dacso@gmail.com references: 1. bernhard, j.d., auspitz sign is not sensitive or specific for psoriasis. j am acad dermatol, 1990. 22(6 pt 1): p. 1079-81. mailto:mara.dacso@gmail.com skin january 2019 volume 3 issue 1 copyright 2018 the national society for cutaneous medicine 48 2. holubar, k. and s. fatović-ferencić, papillary tip bleeding or the auspitz phenomenon: a hero wrongly credited and a misnomer resolved. j am acad dermatol, 2003. 48(2): p. 263-4. 3. shareef, s., et al., acantholysis or the auspitz sign? a revelation of the life of carl heinrich auspitz. indian j dermatol venereol leprol, 2017. 83(4): p. 512. powerpoint presentation presented at the winter clinical dermatology conference hawaii® (wch23), january 13–18, 2023, kohala coast, hi, usa figure 2. patient disposition atwo patients withdrew from the study due to “other” reasons, which was covid-19 disruption. references 1. dong c, et al. j pharmacol exp ther 2016;358:413–422. 2. lebwohl mg, et al. n engl j med 2020;383:229–239. 3. stein gold ls, et al. poster presented at: innovations in dermatology; march 16-20, 2021; virtual. introduction • roflumilast cream, a phosphodiesterase 4 (pde4) inhibitor that is more potent than other pde4 inhibitors,1 was recently approved as a once-daily, nonsteroidal, topical treatment for psoriasis, including intertriginous areas, in patients 12 years of age and older with no limitations on duration of use • in a phase 2b, randomized, double-blind, 12-week trial of 331 adults with chronic plaque psoriasis, roflumilast cream once daily was superior to vehicle cream and was well tolerated2 • the durability of response was assessed in a multicenter, open-label, 52-week study conducted to evaluate long-term safety of roflumilast 0.3% cream in patients with chronic plaque psoriasis methods • this multicenter, open-label, single-arm, long-term, phase 2 safety trial was conducted at 30 centers in the united states and canada • two cohorts of patients were enrolled: cohort 1 patients were those who completed the phase 2b trial through week 12, whereas cohort 2 eligible patients were newly enrolled (treatment-naïve; figure 1) conclusions • in this phase 2 long-term safety study, roflumilast cream 0.3%, a once-daily, nonsteroidal topical pde4 inhibitor, was well-tolerated with a safety profile consistent with the parent phase 2b trial (trial 201) – rates of discontinuations due to aes and lack of efficacy were low – no tachyphylaxis occurred and efficacy was consistent over time (iga success, iga 0/1, and percentage change from baseline in bsa and pasi) – of the 185 patients who achieved iga clear/almost clear during the open-label trial, the median durability of iga of clear/almost clear was 10 months (40.1 weeks) results • patient demographics and clinical characteristics at baseline were similar across cohorts (table 1) • of the 249 subjects who completed trial 201 from sites that participated in this open-label trial, 230 (92.4%) of them enrolled into this study • 244 (73.5%) completed the 202 trial of the 332 patients enrolled across cohort 1 (n=230) and cohort 2 (n=102; figure 2) • percentages of patients achieving investigator global assessment (iga) success and an iga of clear or almost clear were consistent over time (figure 3) mark lebwohl,1 linda stein gold,2 melinda j. gooderham,3 kim a. papp,4 laura k. ferris,5 david n. adam,6 h. chih-ho hong,7 leon h. kircik,8 matthew zirwas,9 patrick burnett,10 robert higham,10 david krupa,10 david berk10 1icahn school of medicine at mount sinai, new york, ny, usa; 2henry ford medical center, detroit, mi, usa; 3skin centre for dermatology, probity medical research and queen’s university, peterborough, on, canada; 4probity medical research and k papp clinical research, waterloo, on, canada; 5university of pittsburgh, department of dermatology, pittsburgh, pa, usa; 6cca medical research, probity medical research and temerty faculty of medicine, university of toronto, toronto, on, canada; 7probity medical research and university of british columbia, department of dermatology and skin science, surrey, bc, canada; 8icahn school of medicine at mount sinai, new york, ny, indiana medical center, indianapolis, in, physicians skin care, pllc, louisville, ky, and skin sciences, pllc, louisville, ky, usa; 9dermatologists of the central states, probity medical research, and ohio university, bexley, oh, usa; 10arcutis biotherapeutics, inc., westlake village, ca, usa durability of efficacy and safety of roflumilast cream 0.3% in adults with chronic plaque psoriasis from a 52-week, phase 2 open-label safety trial figure 1. study design aexcludes scalp, palms, soles. bsa: body surface area; iga: investigator global assessment; qd: once daily; pasi: psoriasis area severity index; sae: serious adverse event; teae: treatment-emergent adverse event. table 1. baseline disease characteristics roflumilast 0.15% and 0.3% → roflumilast 0.3% (n=164) cohort 2 and vehicle → roflumilast 0.3% (n=168) overall total (n=332) bsa, mean % 6.6 6.0 6.3 pasi, mean 7.2 6.3 7.1 iga score, n (%) 1 (almost clear) 0 (0.0) 8 (4.8) 8 (2.4) 2 (mild) 28 (17.1) 40 (23.8) 68 (20.5) 3 (moderate) 124 (75.6) 110 (65.5) 234 (70.5) 4 (severe) 12 (7.3) 10 (6.0) 22 (6.6) intertriginous involvement (i-iga ≥2) i-iga, n (%) 2 (mild) 14 (8.5) 17 (10.1) 31 (9.3) 3 (moderate) 11 (6.7) 18 (10.7) 29 (8.7) 4 (severe) 1 (0.6) 1 (0.6) 2 (0.6) baseline is defined as the last observation prior to the first dose of roflumilast cream in the parent trial (cohort 1 roflumilast 0.3% and roflumilast 0.15% groups) or the current trial (cohort 1 vehicle group and cohort 2). bsa: body surface area; iga: investigator global assessment; i-iga: intertriginous-iga; pasi: psoriasis area severity index. table 2. summary of aes (safety population) teae, n (%) roflumilast 0.15% and 0.3% → roflumilast 0.3% (n=164) cohort 2 and vehicle → roflumilast 0.3% (n=168) overall (n=332) patients with any teae 79 (48.2) 85 (50.6) 164 (49.4) patients with any treatmentrelated teae 4 (1.7) 5 (4.9) 9 (2.7) patients with any sae 8 (4.9) 4 (2.4) 12 (3.6) any treatment-related sae 0 (0) 0 (0) 0 (0) patients who discontinued study drug due to ae 8 (4.9) 5 (3.0) 13 (3.9) treatment-emergent adverse event defined as event with an onset on or after the date of the first study drug application in arq-151-202 study. ae: adverse event; sae: serious adverse event; teae: treatment-emergent adverse event. table 3. most common aes (>2% overall) teae, n (%) roflumilast 0.15% and 0.3% → roflumilast 0.3% (n=164) cohort 2 and vehicle → roflumilast 0.3% (n=168) overall (n=332) upper respiratory tract infection/ viral urti 10 (6.1) 12 (7.1) 22 (6.6) nasopharyngitis 6 (3.7) 6 (3.6) 12 (3.6) urinary tract infection 5 (3.0) 6 (3.6) 11 (3.3) sinusitis 3 (1.8) 5 (3.0) 8 (2.4) ae: adverse event; teae: treatment-emergent adverse event; urti: upper respiratory tract infection. figure 7. mean percent bsa affected observed data. no imputations of missing values. baseline is defined as the last observation prior to the first dose of roflumilast cream in the arq-151-202 study. bsa: body surface area; sd: standard deviation. 2.6 2.3 2.2 2.2 2.2 3.9 2.6 2.4 2.2 2.2 0 1 2 3 4 5 6 7 8 9 10 week 4 week 12 week 24 week 36 week 52 m e a n p a s i s co re roflumilast 0.15% and 0.3% → roflumilast 0.3% (n=164) cohort 2 and vehicle → roflumilast 0.3% (n=168) roflumilast → roflumilast 162 150 136 128 119 vehicle/naive → roflumilast 162 154 140 129 127 201 parent trial baseline mean (sd) bsa: 6.15 (3.9) cohort 2 baseline mean (sd) bsa: 6.6 (5.3) figure 4. percentage of patients with i-iga success over time3,a acohort 1 not shown because i-iga added as study amendment and numbers of patients evaluated are very small at each timepoint. i-iga: intertriginous investigator global assessment; i-iga success: i-iga score of clear or almost clear plus 2-grade improvement from baseline. 42.9 60.0 60.0 56.3 66.7 0 20 40 60 80 100 week 4 (n=21) week 12 (n=20) week 24 (n=20) week 36 (n=16) week 52 (n=15) p a ti e n ts , % roflumilast cream 0.3% n=81 roflumilast cream 0.15% n=83 vehicle cream n=66 completed n=244 (73.5%) roflumilast cream 0.3% n=102 discontinued: 88 (26.5%) withdrew: 36 (10.8%) lost to follow-up: 34 (10.2%) adverse event: 13 (3.9%) lack of efficacy: 3 (0.9%) other: 2 (0.6%)a cohort 1 cohort 2 enrolled n=332 figure 3. percentage of patients achieving (a) iga success and (b) clear or almost clear as observed. no imputation of missing values. baseline is defined as the last observation prior to the first dose of roflumilast cream in the parent trial (cohort 1 roflumilast 0.3% and roflumilast 0.15% groups) or the current trial (cohort 1 vehicle group and cohort 2). iga: investigator global assessment; iga success = iga score of clear or almost clear plus two-grade improvement from baseline. 32.7 36.7 36.0 30.5 35.3 12.9 36.1 29.3 32.0 37.5 0 10 20 30 40 50 60 70 80 90 100 week 4 week 12 week 24 week 36 week 52 p a ti e n ts , % roflumilast 0.15% and 0.3% → roflumilast 0.3% (n=164) cohort 2 and vehicle → roflumilast 0.3% (n=168) roflumilast → roflumilast 162 150 136 128 119 vehicle/naive → roflumilast 163 154 140 129 127 a 40.7 45.3 44.9 39.1 42.0 22.6 48.3 39.1 44.3 47.5 0 10 20 30 40 50 60 70 80 90 100 week 4 week 12 week 24 week 36 week 52 p a ti e n ts , % roflumilast 0.15% and 0.3% → roflumilast 0.3% (n=164) cohort 2 and vehicle → roflumilast 0.3% (n=168) roflumilast → roflumilast 162 150 136 128 119 vehicle/naive → roflumilast 163 154 140 129 127 b figure 6. mean pasi score observed data. no imputation of missing values. pasi assessment was added as an amendment to the trial. pasi: psoriasis area and severity index; sd: standard deviation. 3.37 2.53 2.56 2.57 2.74 3.34 2.5 2.49 2.6 2.37 0 1 2 3 4 5 6 7 8 9 10 week 4 week 12 week 24 week 36 week 52 m e a n p a s i s co re roflumilast 0.15% and 0.3% → roflumilast 0.3% (n=164) cohort 2 and vehicle → roflumilast 0.3% (n=168) roflumilast → roflumilast 17 65 111 128 119 vehicle/naive → roflumilast 101 122 129 129 127 201 parent trial baseline mean (sd) pasi: 7.1 (3.3) cohort 2 baseline mean (sd) pasi: 6.8 (3.3) figure 5. median duration of iga of clear or almost clear duration of iga 0/1: the time from the first observation of iga 0/1 to the first subsequent time a patient’s iga is not iga 0/1. patients who received vehicle in parent study and rolled over into study 202 with a 0/1 assessment are excluded from this analysis (n=324). iga: investigator global assessment. ~57.1% (n=185) of patients achieved iga 0/1 during the trial; patients have a 50% probability of a duration of iga of clear or almost clear of more than 10 months (40.1 weeks) duration of iga clear or almost clear (weeks) 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 p ro b a b il it y i g a c le a r o r a lm o st c le a r 4 12 20 28 360 8 16 24 32 44 56 6440 48 6052 censored 170 138 114 93 69185 166 123 101 82 41 5 063 37 28at risk roflumilast cream phase 2b (trial #201; nct03638258)2 roflumilast cream phase 2 long-term safety (trial #202; nct03764475) eligibility • diagnosis of at least mild plaque psoriasis • age ≥18 years • 2-20% bsaa roflumilast cream 0.3% qd roflumilast cream 0.15% qd vehicle qd endpoints primary: safety • occurrence of teaes • occurrence of saes secondary: efficacy • iga clear or almost clear • intertriginous-iga clear or almost clear • pasi • bsa 12 weeks r a n d o m iz a ti o n 1:1:1 n=331 eligibility • diagnosis of at least mild plaque psoriasis for at least 6 months • age ≥18 years • 2-25% bsa* cohort 1 (rollovers) roflumilast cream 0.3% qd (n=230) 52 weeks cohort 2 (naïve) roflumilast cream 0.3% qd (n=102) completed trial #201 through 12 weeks patients could stop applying treatment to lesions that cleared patients could completely stop treatment when pasi and iga = 0 following an office visit treatment could be resumed when patient-observed psoriasis recurred disclosures ml, lsg, mjg, kap, lkf, dna, hch, lhk, and mz are investigators and/or consultants for arcutis biotherapeutics, inc. and received grants/research funding and/or honoraria; pb, rh, dk, and db are employees of arcutis biotherapeutics, inc. additional disclosures provided on request. acknowledgements • this study was supported by arcutis biotherapeutics, inc. • thank you to the investigators and their staff for their participation in the trial • we are grateful to the study participants and their families for their time and commitment • writing support was provided by by christina mcmanus, phd, alligent biopharm consulting llc, and funded by arcutis biotherapeutics, inc. • among patients with intertriginous area involvement, roflumilast cream provided consistent improvement of intertriginous-investigator global assessment (i-iga; figure 4) • median duration of iga of clear or almost clear was 10 months (figure 5) • a 60.5% mean improvement from baseline in psoriasis area severity index (pasi) and 60.1% mean improvement from baseline in body surface area (bsa) affected were observed at week 12 (figures 6 and 7) – results were consistent through week 52 – median bsa at week 52 was 1.0% • safety was consistent with the parent trial (tables 2 and 3) • 94% of adverse events (aes) were rated mild or moderate in severity • 97% of aes were unrelated or unlikely to be related to treatment as determined by the investigator • ≥97% of patients had no evidence of irritation per investigator local tolerability assessment at each visit (figure 8) figure 8. percentage of patients with investigator-rated tolerability score >0 1.2% 0.6% 1.0% 0.4% 0.0% 0.0% 0 10 20 30 40 50 60 70 80 90 100 baseline week 4 week 12 week 24 week 36 week 52 p a ti e n ts , % overall (n=332) scale for investigator-rated local tolerability (0–7) 0 = no evidence of irritation 1 = minimal erythema, barely perceptible 2 = definite erythema, readily visible; minimal edema or minimal papular response 3 = erythema and papules 4 = definite edema 5 = erythema, edema and papules 6 = vesicular eruption 7 = strong reaction spreading beyond application site n=331 n=324 n=304 n=276 n=255 n=238 slide 1: durability of efficacy and safety of roflumilast cream 0.3% in adults with chronic plaque psoriasis from a 52-week, phase 2 open-label safety trial skin march 2018 volume 2 issue 2 copyright 2018 the national society for cutaneous medicine 155 compelling comments rorschach nevus kevin cao bs a , tyler marion bs mba a , jorge roman md b a the university of texas medical branch school of medicine, galveston, tx b department of internal medicine, texas health presbyterian hospital, dallas, tx in the novel sula by toni morrison, a powerful use of symbolism was expressed in the main antagonist’s skin. sula peace was described as a “heavy brown with large quiet eyes, one of which featured a birthmark that spread from the middle of the lid toward the eyebrow, shaped something like a stemmed rose.”. 1 the most interesting facet of sula’s birthmark is how it is perceived differently by different characters. the shape that other characters perceive her mark perhaps says more about them than about sula. sula’s birthmark functioned as a rorschach test of sorts for various characters in the novel. to the people of the bottom, the predominantly black community in which the characters grow up, sula embodies adventure, freedom, passion, danger, and independence; values that are in stark contrast to the community’s societal norms. as such the people of the bottom despise sula and view her birthmark as something threatening and fearful. the community perceives the mark looks like a snake. to shadrack, who made a living from fishing, sula’s birthmark looked like a tadpole. a world war i veteran suffering from “shell shock”, shadrack undergoes a psychological metamorphosis through the story. to jude, the mark also resembled a snake. symbolic of the serpent in the garden of eden, the mark becomes archetypal of the sin that the married jude commits when he has a sexual affair with sula. in dermatology, the skin has traditionally been portrayed as a window to the internal state of the body. rarely however, do we consider how the skin can give us insight into ourselves, a mirror within the window. conflict of interest disclosures: none. funding: none. corresponding author: jorge roman, md 8200 walnut hill lane dallas, tx 75231 joromanmd@gmail.com references: 1. morrison t. sula. london: vintage; 2004. 2. hirsch m. mother/daughter plot: narrative, psychoanalysis, feminism. bloomington: indiana university press; 1989. skin january 2019 volume 3 issue 1 copyright 2018 the national society for cutaneous medicine 42 short communications bilateral acquired blashkoid dermatitis dathan hamann, md1, catherine ulman, md1 1contact dermatitis institute, phoenix, az 2division of dermatology, ohio state university, columbus, oh acquired blaschkoid dermatitis (abd) is a rare self-limited inflammatory skin disease characterized by eczematous papules and plaques that follow the embryonic migration lines of blaschko. a 68 year old man presented with a 3 month history of ill-defined pruritic rash on the bilateral forearms, ankles, and feet. he had no improvement using antifungals for a presumed diagnosis of tinea corporis with id reaction. skin biopsy demonstrated subacute spongiotic dermatitis with rare eosinophils and dyskeratosis. patch testing to rule out allergic contact dermatitis was negative. he worsened despite systemic and topical steroid therapy and presented 2 months later with a striking non-dermatomal, linear and whorled dermatitis classic for acquired blaschkoid dermatitis (abd) involving the bilateral upper and lower lateral extremities. abd was first reported as “blaschkitis” in 19901 and the nomenclature “acquired relapsing self-healing blaschko dermatitis” was proposed by megahed et al in 1994.2 the similarities between abd and the common childhood dermatosis lichen striatus (ls) has previously cast doubt on abd as a distinct disease entity.3 many dermatologists now generally consider abd and ls to be on a united spectrum of blaschkolinear disease.4 recently, three cases of blaschkoid dermatoses were reported with prominent interface changes,5—which may be the a newly recognized manifestation of the blaschkoid disease spectrum. unlike most dermatitis, abd is rarely steroid-responsive and generally resolves without therapy, though protracted disease courses have been reported. awareness of blaschkoid dermatoses in adults is necessary to distinguish between abd and other diseases with linear morphology such as herpes zoster, linear lichen planus, or linear psoriasis. in children, blaschkoid dermatoses may also be confused with inflamed linear verrucous epidermal nevus. we here present a rare case of bilateral acquired blaschkoid dermatitis. blaschkoid dermatoses are typically limited to 1 extremity and are almost always characterized by a unilateral introduction case report discussion skin january 2019 volume 3 issue 1 copyright 2018 the national society for cutaneous medicine 43 distribution. bilateral ls has been described in several children.6 we here present a rare case of bilateral acquired blaschkoid dermatitis. bilateral ls has been described in several children, but we are unaware of prior reports of bilateral abd. figure 1: a 68 year old man with striking, blaschkoid, linear and whorled dermatitis on bilateral lateral upper and lower extremities. conflict of interest disclosures: none. funding: none. corresponding author: dathan hamann, md contact dermatitis institute phoenix, az dathanhamann@gmail.com references: 1. grosshans e, marot l. blaschkitis in adults. ann dermatol venereol. 1990;117(1):9-15. 2. megahed m, reinauer s, scharffetterkochanek k, et al. acquired relapsing selfhealing blaschko dermatitis. j am acad dermatol. 1994 nov;31(5 pt 2):849-52. 3. hofer t. lichen striatus in adults or 'adult blaschkitis'?. there is no need for a new naming. dermatology. 2003;207(1):89-92. 4. müller cs, schmaltz r, vogt t, et al. lichen striatus and blaschkitis: reappraisal of the concept of blaschkolinear dermatoses. br j dermatol. 2011 feb;164(2):257-62. 5. suárez-peñaranda jm, figueroa o, rodríguez-blanco i, et al. unusual interface dermatoses distributed along blaschko's lines in adult patients. am j dermatopathol. 2017 feb;39(2):144-149. 6. kurokawa m, kikuchi h, ogata k, et al. bilateral lichen striatus. j dermatol. 2004 feb;31(2):129-32. conclusion mailto:dathanhamann@gmail.com powerpoint presentation reduced blood-brain barrier penetration of sarecycline relative to minocycline in rats corresponds with lipophilicity and low vestibular side effects linda stein-gold1, angela moore2,3, s. ken tanaka4, jodi l. johnson5, ayman grada6 1henry ford health system, detroit, michigan, 2baylor university medical center, dallas, texas, usa, 3arlington research center, arlington, texas, usa, 4paratek pharmaceuticals, inc. king of prussia, pennsylvania, usa, 5departments of dermatology and pathology, feinberg school of medicine, northwestern university, usa, 6r&d and medical affairs, almirall (us), exton, pennsylvania, usa email: grada@bu.edu financial support: financial support provided by almirall, llc. introduction methods conclusions results table 1. unlike minocycline, sarecycline was not detectable in the brain in rats results table 2. sarecycline has slightly lower lipophilicity than minocycline and doxycycline discussion table 3. vestibular adverse events were low in phase 3 efficacy and safety studies for sarecycline time mcn-pl scn-pl mcn-br scn-br (hours) µg/ml µg/ml µg/g µg/g 1 0.333 0.460 0.074 blq 3 0.174 0.217 0.139 blq 6 0.077 0.049 0.068 blq pl = plasma, br = brain, mcn = minocycline, scn = sarecycline limit of quantitation (loq) (plasma) = 0.025 µg/ml, loq (brain) = 0.05 µg/g; blq – below the limit of quantitation compound ph 5.5 ph 7.4 sarecycline hcl -0.16 + 0.01 -0.26 + 0.01 doxycycline hcl -0.00 + 0.02 -0.18 + 0.03 minocycline hcl 0.09 + 0.02 0.12 + 0.02 octanol/water distribution coefficients of sarecycline hcl, minocycline hcl, and doxycycline hcl at 25°c. the numbers after ± represent standard deviations obtained from triplicate samples.  sarecycline’s inability to cross the blood-brain barrier compared to minocycline corresponds with sarecycline’s lower lipophilicity and may explain the low rate of vestibular adverse events observed in sarecycline’s clinical trials. discussion table 4. vestibular adverse events were low in an openlabel long-term safety study for sarecycline vestibular effects sarecycline (n=994) placebo (n=996) dizziness 5 (0.5) 11 (1.1) vertigo 0 0 tinnitus 0 0  pooled safety data from 2 identical phase 3 studies (sc1401, sc1402).  12 week double-blind treatment with study visits at 3, 6, 9, and 12 weeks vestibular effects placebo/ sarecycline (n=236) sarecycline/ sarecycline (n=247) total (n=483) dizziness 1 (0.4) 1 (0.4) 2 (0.4) vertigo 0 0 0 tinnitus 0 0 0  patients from previous 12 week phase 3 studies received once daily sarecycline for up to 40 weeks.  sarecycline is an fda-approved narrow-spectrum tetracycline-class oral antibiotic specifically designed for the treatment of moderate-to-severe acne vulgaris.  doxycycline and minocycline have historically been reported with side effects of dizziness, vertigo, or tinnitus.  pooled data from 2 phase iii randomized controlled trials (n=2002) and a 40-week open-label extension study (n=483) for sarecycline reported low rates of vestibular events (dizziness (<0.5%), vertigo (0%), and tinnitus (0%)).  we sought to investigate penetration of the blood-brain barrier of sarecycline relative to minocycline in a rat model and the relative lipophilicity of sarecycline compared to minocycline and doxycycline. table 1. blood-brain barrier penetration: rats (pre-cannulated, jugular vein) were dosed with iv sarecycline or minocycline at a total dose of 1.0 mg/kg. rats were fasted overnight (about 16 hours) prior to dosing and access to food was restored 2 hours after dosing. animals were euthanized via co2 and whole blood (via heart puncture) and brain were collected from 2 rats at each of the following time points: 1, 3 and 6 hr post dosing. table 2. lipophilicity: the octanol/water distribution coefficients (logd) of sarecycline, minocycline, and doxycycline were measured using the shake flask method at ph 5.5 and 7.4 at 25°c. reference: moore a, green lj, bruce s, et al. once-daily oral sarecycline 1.5 mg/kg/day is effective for moderate to severe acne vulgaris: results from two identically designed, phase 3, randomized, double-blind clinical trials. journal of drugs in dermatology: jdd. 2018 sep;17(9):987-96. reference: pariser dm, green lj, lain el, et al. safety and tolerability of sarecycline for the treatment of acne vulgaris: results from a phase iii, multicenter, open-label study and a phase i phototoxicity study. journal of clinical and aesthetic dermatology. 2019;12(11):e53-e62. mailto:grada@bu.edu slide number 1 improvement of nail psoriasis with brodalumab in phase 3 trials mark g. lebwohl,1 lawrence green,2 sylvia hsu,3 shipra rastogi,4 tina lin,5 radhakrishnan pillai,6 robert j. israel5 1icahn school of medicine at mount sinai, new york, ny; 2george washington university school of medicine, washington, dc; 3baylor college of medicine, houston, tx; 4ortho dermatologics, bridgewater, nj; 5valeant pharmaceuticals north america llc, bridgewater, nj; 6dow pharmaceutical sciences (a division of valeant pharmaceuticals north america llc), petaluma, ca 2017 fall clinical dermatology conference® • october 12-15, 2017 • las vegas, nv introduction • psoriasis is a chronic inflammatory condition characterized by thick, scaly patches on the skin – interleukin-17 (il-17) has been identified to play a significant role in disease pathogenesis1 • nail involvement occurs in approximately half of all patients with psoriasis and is often difficult to treat2 • brodalumab is a monoclonal antibody that targets the receptor il-17ra and has demonstrated efficacy and safety in the treatment of plaque psoriasis3,4 objective • to evaluate the efficacy of brodalumab in nail psoriasis methods • brodalumab was evaluated in three phase 3 multicenter, randomized, double-blind, placebo-controlled studies in patients with moderate-to-severe psoriasis3,4 • patients were treated with brodalumab (140 or 210 mg every 2 weeks [q2w]) or placebo during the 12-week induction phase • nail involvement was assessed at baseline using the nail psoriasis severity index (napsi) – patients were evaluated by the nail with the highest psoriasis involvement score • improvement in napsi score was assessed in patients with a baseline napsi score ≥6 • the mean improvement in napsi score from baseline was evaluated at week 12 • comparisons were made by analysis of covariance, adjusting for baseline body weight, prior biologic use, geographic region, study, and baseline napsi score results patient demographics and characteristics • mean baseline napsi scores were similar in all groups (range, 9.5-9.6; table 1) improvement in napsi score at week 12 • the improvements observed with both brodalumab doses compared with placebo were significant (p<0.001; figure 1) • after 12 weeks, improvements from baseline of 11.6%, 37.5%, and 46.3% were observed in the placebo, brodalumab 140 mg q2w, and brodalumab 210 mg q2w groups, respectively (figure 2) • after 12 weeks, treatment with brodalumab 210 mg q2w led to a greater decrease in napsi score compared with brodalumab 140 mg q2w relative to placebo (table 2) table 1. patient baseline demographics and clinical characteristics (integrated amagine-1/-2/-3 studies) figure 1. napsi score at baseline and week 12 (as observed). n a ps i s co re , m ea n (s d ) 6 0 4 2 10 12 14 8 bl bl * blweek 12 week 12 week 12 brodalumab 140 mg q2w placebo brodalumab 210 mg q2w 261n 466 472 1.1 (3.2)improvement over baseline(as observed), mean (sd) 3.6 (3.9) 4.4 (3.8) 5.16.08.4 9.59.69.5 * bl, baseline; napsi, nail psoriasis severity index; q2w, every 2 weeks; sd, standard deviation. *p<0.001 vs bl. figure 2. percent improvement over baseline at week 12 (as observed). n a ps i s co re im pr ov em en t ov er b as el in e, % 30 0 20 10 50 60 40 placebo 11.6% 37.5% 46.3% brodalumab 140 mg q2w brodalumab 210 mg q2w 261 n466 472 napsi, nail psoriasis severity index; q2w, every 2 weeks. acknowledgments: this study was sponsored by ortho dermatologics. medical writing support was provided by medthink scicom and funded by ortho dermatologics. references: 1. kim and krueger. annu rev med. 2017;68:255-269. 2. crowley et al. jama dermatol. 2015;151:87-94. 3. lebwohl et al. n engl j med. 2015;373:1318-1328. 4. papp et al. br j dermatol. 2016;175:273-286. conclusions • brodalumab 140 and 210 mg q2w were associated with significant improvements in psoriatic nail symptoms after 12 weeks of treatment • because nail turnover is slower than skin turnover, longer periods of brodalumab therapy would be expected to result in continued nail improvement brodalumab placebo (n=844) 140 mg q2w (n=1458) 210 mg q2w (n=1458) age, mean (sd), y 44.7 (12.9) 44.8 (13.0) 45.1 (12.9) male, n (%) 588 (69.7) 1012 (69.4) 1013 (69.5) white, n (%) 769 (91.1) 1322 (90.7) 1319 (90.5) weight, mean (sd), kg 90.2 (22.1) 90.4 (21.6) 90.7 (23.1) bmi, mean (sd), kg/m2 30.2 (6.8) 30.4 (7.0) 30.5 (7.3) duration of psoriasis, mean (sd), y 18.5 (12.0) 18.1 (11.9) 18.7 (12.4) psoriatic arthritis (yes), n (%) 173 (20.5) 319 (21.9) 299 (20.5) bsa, mean (sd), % 27.6 (17.1) 27.8 (17.8) 26.8 (16.8) pasi score, mean (sd) 20.1 (8.3) 20.2 (8.2) 20.2 (8.0) spga score, n (%) 3 4 5 (very severe) 473 (56.0) 324 (38.4) 47 (5.6) 899 (61.7) 489 (33.5) 70 (4.8) 810 (55.6) 567 (38.9) 81 (5.6) prior biologic therapy (yes), n (%) 267 (31.6) 438 (30.0) 439 (30.1) napsi score, mean (sd) 9.5 (3.4) 9.6 (3.9) 9.5 (4.0) patients with napsi ≥6, n (%) 261 (30.9) 466 (32.0) 472 (32.4) bmi, body mass index; bsa, body surface area; napsi, nail psoriasis severity index; pasi, psoriasis area and severity index; q2w, every 2 weeks; sd, standard deviation; spga, static physician’s global assessment. table 2. treatment differences with brodalumab vs placebo at week 12 (multiple imputation) brodalumab placebo (n=261) 140 mg q2w (n=466) 210 mg q2w (n=472) napsi, mean (se) 8.5 (0.3) 6.0 (0.2) 5.2 (0.2) treatment difference vs placebo, least squares mean (95% ci) — 2.5 (2.0, 3.0) 3.3 (2.8, 3.8) p value vs placebo <0.001 <0.001 ci, confidence interval; napsi, nail psoriasis severity index; q2w, every 2 weeks; se, standard error. © 2017. all rights reserved. 7589_napsi (aad encore)_m1-1.indd 1 9/22/17 9:41 am fc17postervaleantlebwohlimprovementnailpsoriasisphase3.pdf skin november 2017 volume 1 issue 3 copyright 2017 the national society for cutaneous medicine 150 brief articles timolol for treatment of recalcitrant pyogenic granulomas: a case report and review of the literature paige hoyer bs a , priscilla ly bs a , lindy ross md b , michael wilkerson md b a the university of texas medical branch at galveston, school of medicine b the university of texas medical branch at galveston, department of dermatology pyogenic granuloma (pg) is a benign vascular tumor also known as a lobular capillary hemangioma. it grows rapidly on the skin or mucosal surfaces, commonly affecting the face, oral mucosa, and sites of previous injury. pgs appear as a solitary, pedunculated lesion with a friable surface that bleeds easily. 1 though some pgs resolve spontaneously, treatment is often warranted to prevent bleeding, ulceration, and scarring. current treatment techniques include cryotherapy, laser, electrodessication, curettage or shave excision, sclerotherapy, corticosteroid abstract importance: pyogenic granuloma (pg) is a benign vascular tumor that forms commonly on the face, oral mucosa, or a site of previous injury. though some pgs resolve spontaneously, most require some-to-multiple form(s) of treatment to prevent bleeding, ulceration, and scarring. current treatment options for pgs include cryotherapy, laser, electrodessication, curettage or shave excision, sclerotherapy, corticosteroid injections, and imiquimod 5% cream. timolol 0.5% ophthalmic solution has been used as a noninvasive topical treatment for pg in the pediatric population. objective: to present a case of successful treatment of a recalcitrant pg with topical timolol, and to report on the current literature for similar cases. case presentation: we present a case of a 40-year-old healthy female who developed a biopsy-proven pg on her index finger. this is the first reported case to successfully use tangential biopsy and electrodessication followed by twice daily topical timolol to treat recalcitrant pg. conclusions: this case supports the use of 0.5% timolol ophthalmic solution and demonstrates that it is a safe and economical therapy for adult patients with recurrent pgs. a review of the current literature is discussed and supports timolol as an easy and economical therapy option. introduction skin november 2017 volume 1 issue 3 copyright 2017 the national society for cutaneous medicine 151 injections, and imiquimod 5% cream either alone or in combination. 2 unfortunately, these treatment options have been associated with pain, scarring, or other side effects. 3 this poses a challenge when dealing with pediatric patients or when treating on sensitive areas like the face. beta blockers, such as propranolol, have shown great success in reducing the size of vascular tumors like hemangiomas. 4 the exact mechanism of growth inhibition on capillary tumors by beta blockers is unknown. it is thought that they inhibit growth through four main mechanisms: vasoconstriction, inhibition of angiogenesis, induction of apoptosis, and recruitment of endothelial progenitor cells. 5,6 timolol 0.5% ophthalmic solution is thought to work similarly on pyogenic granulomas and has been reported as an effective noninvasive treatment option for multiple cases. 6 we report a challenging case of a woman with recalcitrant pg that was successfully treated with topical timolol. a 40-year-old caucasian female presented to the dermatology clinic in november 2015 for the evaluation of a bump on her right index finger (figure 1a, b). she denied any previous injury to the site. a tangential biopsy was performed and histopathology of the lesion was consistent with pyogenic granuloma. hemostasis was obtained with aluminum chloride, and electrodessication was performed. when the patient returned to clinic 1 month later, the lesion had regrown and was treated with a second tangential excision, repeat electrodessication, and a 5 mg/ml intralesional kenalog injection into the base of the lesion. three months later, the patient reported regrowth of the lesion and returned to clinic. after reviewing the literature, a trial of timolol 0.5% ophthalmic solution twice daily was started. the lesion did not improve with timolol 0.5% twice daily alone, and the patient returned to clinic 2 weeks later with continued bleeding and pain. the recurrent lesion was treated with a third tangential excision with electrodessication, and the patient was instructed to apply one drop of timolol 0.5% ophthalmic solution to the base of the lesion twice daily. one month follow up via telephone revealed the lesion had not recurred and the patient reduced her timolol applications to once daily. per our request during the one month telephone follow up, the patient sent photos of the nearly resolved lesion to the clinic. (figure 2a, b) case presentation a. figure 1: recurrent pyogenic granuloma after two shave excisions b. skin november 2017 volume 1 issue 3 copyright 2017 the national society for cutaneous medicine 152 pyogenic granuloma (pg) can be difficult to treat and often recurs. treatment options generally include one or more of the following options: cautery, laser, excision, curettage, sclerotherapy, or cryotherapy. imiquimod 5% cream is a less invasive option for treating pg, but it can be limited by its adverse effects of crusting, superficial scarring, and dyspigmentation. 7 based on our review of the literature, timolol 0.5% ophthalmic solution has been utilized as either a primary or adjunctive therapy for pgs. timolol is a beta-adrenergic receptor blocker, which is hypothesized to work similarly to propranolol, which can be used to treat cutaneous vascular tumors such as hemangiomas. 4 it is thought to work through local blockade of the vascular beta receptors, resulting in vasoconstriction, decreased vascular growth factors, and decreased blood flow into the vascular tumor which inhibits growth and proliferation. 5,6 noninvasive topical timolol is an important alternative for the treatment of pgs in pediatric patients who cannot undergo invasive procedures for pgs located on sensitive areas such as the face. topical application of timolol is not associated with systemic side effects of beta adrenergic blockers and does not require any monitoring. 8 treatment is often painless, noninvasive, and cheap compared to alternate therapies. we present the first reported case to successfully treat pgs using tangential biopsy and electrodessication followed by twice daily topical timolol. there are currently 19 cases, 5 adult and 14 pediatric, in the literature that have shown improvement or complete resolution of pg with either timolol alone or as adjuvant therapy (table 1). our case and review of the current literature suggests that topical timolol 0.5% ophthalmic solution may be an effective single agent or adjunctive therapy for primary and recurrent pyogenic granuloma in both children and adults. more studies are needed in this area of research to provide additional evidence that supports this treatment. discussion figure 2: patient-provided follow-up images of resolution of pyogenic granuloma b. a. skin november 2017 volume 1 issue 3 copyright 2017 the national society for cutaneous medicine 153 table 1. previously reported cases of pyogenic granulomas treated with timolol author / year age (yrs) sex location diameter (mm) treatment treatment duration treatment response wine l, et a.l 2013 (6) 32 mos f cheek n/a curettage + 0.5% timolol gfs (bid) 6 months complete resolution 4 f cheek n/a 2% timolol gfs (bid) 2 months partial response at 2 months, resolution at 3 months 6 m lower eyelid n/a 2% timolol gfs (tid) 2 months partial response at 2 months, near resolution at 4 months 7 f medial canthus n/a 2% timolol gfs (tid) 6 weeks partial response 8 m scalp n/a 0.5% timolol gfs (tid) 12 weeks partial response at 6 weeks, complete resolution 5 f forearm n/a electrocautery → 2% timolol gfs (tid) 8 weeks partial response 6 m buccal mucosa n/a excision x4, intralesional triamcinolone, potassium titanyl phosphate laser → propranolol 2mg/kg/day (bid) 6 months resolution khorsand k, et a. 2014 (11) 5 mos f cheek 7mm 0.5% timolol gfs 0.5% timolol gfs 1 month 8 months mild improvement complete resolution malik m, et al. 2014 (13) 14 n/a finger n/a 0.5% timolol gfs (bid) 3 weeks complete resolution after 7 months milsop jw, et al. 2014 (2) 39 m scalp 50mm acticoat 7-silver coated low adherent primary wound dressing → 5% topical imiquimod (qhs), 1% topical clindamycin (bid), oral doxycycline 100mg (bid) → pulsed dye laser + 0.5% timolol gfs + oral doxycycline 100mg (bid) → vascular laser + silver nitrate + intralesional injections of triamcinolone acetonide (10mg/ml) → vascular lasers + intralesional steroids + 0.5% timolol gfs 2 weeks 1 month 4 weeks 3 months no improvement mild improvement improvement + intermittent bleeding complete resolution resenstein r, et al. 2015 (14) 39 f periungual n/a 0.5% timolol gfs (1-2x daily) + mupirocin (prn) 1 month complete resolution skin november 2017 volume 1 issue 3 copyright 2017 the national society for cutaneous medicine 154 table 1 (continued). previously reported cases of pyogenic granulomas treated with timolol author / year age (yrs) sex location diameter (mm) treatment treatment duration treatment response gupta d, et al. 2016 (10) 26 m finger 7mm 0.5% timolol maleate (ii gtt qid) 3 days complete resolution 20 f lip 6mm 0.5% timolol maleate (ii gtt qid) 2.5 months partial response 16 m scalp 13mm 0.5% timolol maleate (ii gtt qid) 22 days complete resolution 16 m arm 30mm 0.5% timolol maleate (ii gtt qid) 24 days complete resolution 50 m scalp (multiple) 1-4mm 0.5% timolol maleate (ii gtt qid) 16 days complete resolution of smaller papules. no response of other lesions 15 m abdomen 4mm 0.5% timolol maleate (ii gtt qid) 12 days partial response chiriac a, et al. 2016 (9) 2 m palpebral area n/a 0.1% timolol in occlusive dressing (bid) + 2 applications of 70% trichloroacetic acid (1 every 7 days) 2 weeks complete resolution 13 mos f face n/a 0.1% timolol in occlusive dressing (bid) + 1 application of 70% trichloroacetic acid 2 weeks complete resolution knöpfel m, et al. 2016 (12) 2 m scalp n/a 0.5% timolol gfs (bid) 1 month almost complete resolution hoyer p, et al. 2017 40 f finger n/a electrodessication → electrodessication + kenalog 5mg/ml → 0.5% timolol gfs (bid) → electrodessication + 0.5% timolol gfs (bid) 1 month 1 month 2 weeks 1 month regrowth of lesion regrowth of lesion bleeding and pain complete resolution topical timolol was an effective treatment for our case of pyogenic granuloma. no side effects were associated with the treatment and a complete resolution of the lesion was observed. our case report supports the use of 0.5% timolol ophthalmic solution as a safe and cost effective adjunctive option for pg therapy. our review of the literature suggests that topical timolol may be effective as a single agent or as adjunctive treatment for primary and recurrent pgs in both pediatric and adult populations. more studies are needed in this area of research to provide additional evidence that supports this treatment. conflict of interest disclosures: none. funding: none. corresponding author: paige hoyer, bs 301 university blvd galveston, tx 77551 512-968-5742 pehoyer@utmb.edu conclusion skin november 2017 volume 1 issue 3 copyright 2017 the national society for cutaneous medicine 155 references: 1. walsh j, eady j. vascular tumors. hand clinics. 2004;20(3):261-268. 2. millsop jw, trinh n, winterfield l., berrios r., hutchens ka., tung r. resolution of recalcitrant pyogenic granuloma with laser, corticosteroid, and timolol therapy. dermatology online journal. 2014;20(3). . 3. gilmore a, kelsberg g, safranek s. clinical inquiries. what's the best treatment for pyogenic granuloma? j fam pract. 2010;59:40-2. 4. leaute-labreze c, dumas de la roque e, hubiche t., et al. propranolol for severe hemangiomas of infancy. n engl j med. 2008;358(24):2649–2651. 5. shah s, frieden ij. treatment of infantile hemangiomas with beta-blockers: a review. skin therapy letter. 2013;18(6):5-7. 6. wine lee l, goff kl, lam jm, low dw, yan ac, castelo-soccio l. treatment of pediatric pyogenic granulomas using b-adrenergic receptor antagonists. pediatr dermatol. 2013;31(2):203-7. 7. qiu y, ma g, yang j, et al. imiquimod 5% cream versus timolol 0.5% ophthalmic solution for treating superficial proliferating infantile haemangiomas: a retrospective study. clin exp dermatol. 2013;38(8):845–850. 8. chakkittakandiyil a, phillips r, frieden ij, siegfried e, lara-corrales i, lam j, et al. timolol maleate 0.5% or 0.1% gel-forming solution for infantile hemangiomas: a retrospective, multicenter, cohort study. pediatr dermatol. 2011;29:28-31. 9. chiriac a, birsan c, podoleanu c, moldovan c, brzezinski p, stolnicu s. noninvasive treatment of pyogenic granulomas in young children with topical timolol and trichloroacetic acid, the journal of pediatrics. 2016;169:322. 10. gupta d, singh n, and thappa dm. is timolol an effective treatment for pyogenic granuloma? int j dermatol. 2016;55(5):592-5. 11. khorsand k, maier m, and brandling-bennett ha. pyogenic granuloma in a 5-month-old treated with topical timolol. pediatr dermatol. 2014;32(1):150-1. 12. knöpfel m, escudero-góngora m, bauzà a, martín-santiago a. timolol for the treatment of pyogenic granuloma (pg) in children. journal of the american academy of dermatology. 2016;75(3):105-106. 13. malik m, murphy r. a pyogenic granuloma treated with topical timolol. british journal of dermatology. 2014;171(6):1537-8. 14. resenstein r, lewellis s, leger m. periungual pyogenic granuloma formation in a patient with complex regional pain syndrome. dermatology online journal. 2015;21(12). skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 140 covid concept use of absorbable cutaneous sutures amid the covid-19 pandemic paige hoyer, md1, julie a. croley, md1, richard f. wagner, jr., md1 1the university of texas medical branch at galveston, department of dermatology, galveston, tx absorbable cutaneous sutures are an option for dermatologic surgeons to decrease the number of times “high risk” patients return to the clinic, eliminating additional potential exposures for patients, surgeons, and medical staff to covid-19. an 88 year old woman with multiple comorbidities presented to the mohs surgery service for treatment of a primary welldifferentiated squamous cell carcinoma of the left nasal supratip. her final wound size was 1.0 cm x 0.7 cm. after discussion with the patient, a primary closure was pursued. she was very anxious about returning to the clinic for suture removal, and absorbable surface sutures as an alternative to traditional non-absorbable sutures was preferred by the patient. absorbable 4-0 buried poliglecaprone-25 sutures were used to close the superficial fascia and dermal layers. absorbable simple interrupted 5-0 plain gut surface sutures were used to further approximate the wound edges (figure 1). the patient was advised that plain gut surface sutures typically dissolve within 10-14 days with routine postoperative care. the patient returned three weeks later for an additional mohs surgery procedure at a separate site. she had a well-healed scar, and stated she was satisfied with the cosmetic result of the nasal repair using absorbing sutures (figure 2). studies have shown no significant difference in cosmetic outcomes between polypropylene non-absorbing suture and plain gut absorbable suture.1,2,3 many patients express anxiety over the thought of suture removal, and often ask if the sutures will dissolve on their own during the surgery. use of absorbable epicuticular sutures is one way surgeons can help allay this fear, and studies have shown similar patient abstract the use of absorbable epicuticular sutures is highlighted as a measure to decrease the number of patient visits, eliminating the risk of additional exposures for patients and medical staff during the covid-19 pandemic. we present a case where the use of absorbable epicuticular sutures was preferred over non-absorbable sutures. studies have shown no significant difference in cosmetic outcomes between non-absorbing suture and absorbable suture. many patients express anxiety over the thought of suture removal, and often ask if the sutures will “dissolve on their own” during the surgery. use of absorbable top sutures is one way surgeons can help allay this fear, and studies have shown similar patient satisfaction between absorbable and non-absorbable sutures. additional stress may be prominent during the current pandemic. dermatologic surgeons should strongly consider the use of absorbable cutaneous sutures during this pandemic, as this likely improves patient and staff safety, and studies have shown similar cosmetic outcomes and patient satisfaction. skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 141 satisfaction between absorbable and nonabsorbable sutures.4 additional stress may occur during the current covid-19 pandemic, especially for patients considered high risk by cdc. the cdc initially identified patients over the age of 65 as high risk for covid-19 mortality, but have now clarified that patients of all ages, including pediatric populations, can sustain significant morbidity from this virus. however, those over the age of 65 are more likely to have comorbidities.5 patients with chronic kidney disease, type 2 diabetes, chronic obstructive pulmonary disease, obesity, compromised immune systems (e.g. solid organ transplant patients), and heart disease are at a much higher risk of significant morbidity and mortality from covid-19.5 the american academy of dermatology recommends the use of absorbable sutures during the current pandemic as well.6 we requested that patients who did not return for in-person follow up, upload postop photos via our patient portal system. these photos were then reviewed by the surgeons involved in the case. along with the photos the patients were able to report any symptoms they may be having. wounds were evaluated for healing, bleeding, cosmesis, and infection. additionally, the mohs medical assistant called all post-op patients 1 week after surgery to check in. no post-op wound infections occurred in this population, and all patients expressed satisfaction with their procedure. dermatologic surgeons should consider the use of absorbable cutaneous sutures during this pandemic in appropriate patients, especially for patients at higher risk for covid-19 morbidity and mortality. this intervention likely improves safety for patients, physicians and medical staff, and studies have shown similar cosmetic outcomes and patient satisfaction. figure 1. immediately post-op. figure 2. two weeks post-op, well-healed scar. conflict of interest disclosures: none funding: none corresponding author: paige hoyer, md 301 university blvd. 4.112, mccullough building galveston, tx 77555 skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 142 phone: 409-747-3376 fax: 409-772-4456 email: pehoyer@utmb.edu references: 1. xu b, xu bo, wang l, chen, c, et al. absorbable versus nonabsorbable sutures for skin closure: a meta-analysis of randomized controlled trials. ann of plas surg. 2016;76(5):598-606. 2. luck r1, tredway t, gerard j, eyal d, et al. comparison of cosmetic outcomes of absorbable versus nonabsorbable sutures in pediatric facial lacerations. pediatr emerg care. 2013;29(6):6915. 3. guyuron b, vaughan c. a comparison of absorbable and nonabsorbable suture materials for skin repair. plast reconstr surg 1992;89:234– 6. 4. aboul-fettouh n, marzolf s, smith jm, srivastava d, et al. patient satisfaction and preference for absorbable versus nonabsorbable sutures for linear repairs. j am acad dermatol. 2018;79(3):561-562. 5. cdc. cdc updates, expands list of people at risk of severe covid-19 illness. jun 7, 2020. accessed sept. 9, 2020. <https://www.cdc.gov/media/releases/2020/p062 5-update-expands-covid-19.html> 6. der sarkissian s, kim l, veness m, yiasemides e, et al. “recommendations on dermatologic surgery during the covid-19 pandemic.” j am acad dermatol. 2020;83(1):e29-e30. mailto:pehoyer@utmb.edu http://qxmd.com/r/23714755 http://qxmd.com/r/23714755 http://qxmd.com/r/23714755 https://www.cdc.gov/media/releases/2020/p0625-update-expands-covid-19.html https://www.cdc.gov/media/releases/2020/p0625-update-expands-covid-19.html clinical impact of a 31-gene expression profile test on physician recommendations for management of melanoma patients in a prospectively tested cohort martin fleming, md1, clare johnson, rn2, kyle covington, phd2, joseph gadzia, md3, larry dillon, md4, federico a. monzon, md2 1the university of tennessee health science center, memphis, tn; 2castle biosciences, inc., friendswood, tx; 3kansas medical clinic, topeka, ks; 4dr. larry dillon, colorado springs, co background • a 31-gene expression profile (gep) test which identifies cutaneous melanoma tumors as low risk (class 1) or high risk (class 2) of metastasis has been clinically validated.1-4 • the test has been shown to influence physicians to direct clinical management of cutaneous melanoma patients in several clinical use studies (table 1).5-7 • to further assess the clinical impact of the gep test, we undertook a study to evaluate and compare clinical management plans prospectively, including initial workup, follow-up intervals, and referral patterns, established by physicians prior to and after gep testing. • here we present preliminary results of this multicenter, prospective clinical utility study to determine the clinical impact of the gep test on patient management plans. results table 2. cohort demographics conclusions • overall, 46% of tested patients had a change in clinical management • the majority of reported management changes were in a risk-appropriate direction, with 81% of decreases in care provided to lowrisk class 1 patients and 87% of increases in care provided to high-risk class 2 patients • physicians used gep results to individualize management based on biological risk, as determined by the test, while still remaining within the context of established practice guidelines • results of this prospective study show that the accurate identification of risk provided by the gep informs appropriate clinical management and patient care. the change in management is similar to three additional clinical utility studies. references 1. gerami p, et al. clin cancer res 2015;21:175-83. 2. gerami p, et al. j am acad dermatol 2015;72:780-5 e783. 3. zager js, et al. j clin oncol 2017;34:9581. 4. hsueh ec, et al. j hematol oncol 2017;10:152. 5. berger ac, et al. curr med res opin 201632:1599-604. 6. farberg as, et al. j drugs dermatol 2017;16:428-31. 7. schuitevoerder d, et al. ann surg oncol 2017;24:s144. disclosures cj, kc and fam are employees and stockholders of castle biosciences, inc. the proprietary gep test is clinically available through castle biosciences as the decisiondx®-melanoma test (www.skinmelanoma.com). table 3. clinical and molecular features across treatment groups clinical characteristics overall n=127 median age (range), years 63 (28-95) t stage t1 61 (48%) t2 32 (25%) t3 17 (13%) t4 8 (6%) not reported 9 (7%) breslow thickness median (range), mm 1.0 (0.1-18.0) ≤1 mm 66 (52%) >1 mm 61 (48%) mitotic index <1/mm2 78 (61%) ≥1/mm2 49 (31%) ulceration absent 103 (81%) present 20 (16%) growth pattern superficial spreading 30 (24%) nodular 16 (13%) desmoplastic 6 (5%) lentigo maligna 3 (2%) other/not assessed 72 (56%) site trunk 43 (34%) extremity 66 (52%) head and neck 18 (14%) gep result class 1 96 (76%) class 2 31 (24%) feature dermatology n=41 surgical oncology n=82 medical oncology n=4 breslowa* 0.5 (0.1-4.9) 1.2 (0.0-7.5) 1.7 (0.2-18.0) ulcerationb absent 88% (36) 78% (64) 75% (3) present 12% (5) 17% (14) 25% (1) mitosisb <1/mm2 68% (28) 60% (49) 25% (1) ≥1/mm2 32% (13) 40% (33) 75% (3) gep classb class 1 83% (34) 71% (58) 100% (4) class 2 17% (7) 29% (24) 0% (0) class 1 class 2 decrease increase decrease increase labs* 3 0 1 7 imaging* 4 0 2 14 adjuvant 0 0 0 1 visits* 14 4 0 10 referral* 13 2 3 6 amedian (range), bpercent (count), *p<0.001 *p≤0.005, fisher’s exact test figure 1. number of cases increasing or decreasing intensity of management by gep class table 4. frequency of each modality of change in patients with decreases or increases in intensity of clinical management figure 2. schematic representation of risk stratification using ajcc stage with gep test result to guide patients’ clinical management melanoma staging (per nccn) decisiondx low risk: class 1 decisiondx high risk: class 2 increase intensity (trials) decrease intensity continue high intensity mgmt (encourage trials) decisiondx low risk: class 1 decisiondx high risk: class 2 low intensity mgmt (derm) ajcc low risk stage i, iia ajcc high risk stage iib, iic, iii early detection of recurrence appropriate treatment or clinical trial methods • the rt-pcr-based gep test was performed using primary tumor tissue. metastatic risk class was determined using a proprietary predictive modeling algorithm which provides a binary classification of class 1 (low risk) or class 2 (high-risk). • at initial evaluation, prior to gep testing, each patient’s baseline data was assessed. physicians’ pre-test recommendations for follow-up were collected and categorized as laboratory tests (labs), imaging, clinical visits, adjuvant treatment discussion, and referral to surgical or medical oncology. • at the subsequent visit following receipt of gep test result, follow-up recommendations were again collected to capture any changes in management. • changes were categorized as increases, decreases or no change based on comparison of management plans preand post-receipt of gep test result. study result berger (2016)5 prospective, multicenter n patients = 163 53% changed mgmt after inclusion of gep result farberg (2017)6 dermatologist survey n physicians = 169 47-50% changed mgmt after inclusion of gep result schuitevoerder (2017)7 prospective, single center n patients = 91 52% of mgmt decision based on gep result using decision tree model table 1. management changes in three clinical use studies methods • of 204 patients enrolled in the study, 127 patients from 15 dermatology, medical oncology and surgical oncology centers completed study participation at time of censoring (june 30, 2017). of 36 class 1 patients who changed, 81% had reduced surveillance intensity and/or referral of 23 class 2 who changed, 86% had increased surveillance intensity and/or referral overall 46% of patients (59/127) had a documented change in management following test result class 1: 38% (36/96) of patients changed class 2: 74% (23/31) of patients changed fc17postercastlebiosciencesflemingclinicalimpact.pdf skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 102 brief articles lues maligna in an immunocompetent male carly dunn, ba1; danielle s. applebaum, md2 1school of medicine, baylor college of medicine, houston, texas 2baylor college of medicine, department of dermatology, houston, texas syphilis, a sexually transmitted disease from the spirochete treponema pallidum, is often referred to as the “the great imitator” because of its plethora of clinical presentations.1,2 lues maligna (malignant syphilis) is a rare, aggressive variant of secondary syphilis predominately found in patients with immunodeficiency; however, it has also been described in patients with chronic alcohol or drug abuse, tuberculosis, or diabetes mellitus.1 we present a case of an immunocompetent patient diagnosed with lues maligna. a 29-year-old immunocompetent african american male presented with diffuse, painful, boils for two weeks. the rash originated as a single bullous lesion and became generalized despite empiric treatment with cephalexin for ten days. he had no past medical history. the patient was afebrile, and physical examination revealed widespread hyperpigmented papules, nodules, and ulcerated papulonodules with overlying crusts on his torso, buttocks, and extremities as shown in figure 1. biopsy of a lesion on his back revealed an inflammatory crust, necrosis in the epidermis and mid-dermis, and a wedge-shaped mononuclear infiltrate containing eosinophils in the deep dermis. the biopsy was initially read as consistent with pleva. prior to initiation of methotrexate for pleva, laboratory examination revealed a positive rpr. hiv testing was negative. the patient was diagnosed with lues maligna given his lues maligna (malignant syphilis) is an aggressive, rapidly developing, rare variant of secondary syphilis and is characterized by flu-like prodromal symptoms followed by an eruption of irregularly scattered erythematous papules and pustules that quickly progress into well-defined necrotic ulcers. atypical presentations of syphilis, such as lues maligna, occur more commonly in hiv-positive and immunocompromised individuals. we present a rarer case of an immunocompetent patient with lues maligna. syphilis mimics many other conditions and it is easily treatable once diagnosed. therefore, dermatologists should think beyond pityriasis rosea-like rashes and consider syphilis when patients present with lesions that resemble pityriasis lichenoides et varioliformis acuta (pleva), drug eruption, disseminated herpes or zoster infection, cutaneous t-cell lymphoma, and ulcerating vasculitis. abstract introduction case report skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 103 figure 1: multiple ulcerated and necrotic papulonodules with a secondary hemorrhagic crust as well as hyperpigmented macules. clinical, histopathologic, and positive rpr. the patient experienced complete resolution in two to three weeks with enduring postinflammatory hyperpigmentation after treatment with a single dose of benzathine penicillin g 2.4 million units intramuscularly. syphilis progresses from primary to secondary to tertiary syphilis; however, at each stage the presentation can deviate. secondary syphilis can be variable, including, but not limited to: diffuse maculopapular rash that involves the palms and soles with lymphadenopathy, highly infectious condyloma lata, syphilitic hepatitis, mild constitutional symptoms, and/or bone pain1. lues maligna (malignant syphilis) is an aggressive, rapidly developing, rare variant of secondary syphilis and is characterized by flu-like prodromal symptoms followed by an eruption of irregularly scattered erythematous papules and pustules that quickly progresses into well-defined necrotic ulcers. the lesions most commonly present with a pityriasis rosea-like eruption, are polymorphic, often involve the scalp and face, and can become covered with a dark, rupioid crusterror! bookmark not defined.,2. atypical presentations of syphilis, such as lues maligna, commonly occur in hivpositive and immunocompromised individualserror! bookmark not defined.,error! bookmark not defined.,. a retrospective, multicenter study of 11,368 patients with hiv revealed that 1.3% of them had concurrent syphilis and of those 7.3% had lues maligna.2 another retrospective study by romero-jimenez found that approximately 80% of patients with lues maligna had a concurrent aids-defining illness with cd4 counts less than 200 cells/ml3. however, it is thought that a functional, rather than quantitative deficit is responsive for its aggressive presentation, as many cases of lues maligna are seen in individuals with cd4 counts greater than 200 cells/ml.1 characteristic histologic findings are similar to other presentations of secondary syphilis and include epidermal necrosis, dense perivascular and interstitial inflammation, lymphocyte and plasma cell invasion, and vascular changeserror! bookmark not defined.,error! bookmark not defined.. the vessel involvement spans from endothelial swelling and/or proliferation, hyaline thrombi, and fibrinoid deposition i . along with clinical and histologic findings, immunohistochemical staining can identify spirochetes thus aiding in diagnosiserror! bookmark not defined.. the differential diagnosis for malignant syphilis includes disseminated herpes simplex or zoster, pityriasis lichenoides et varioliformis acuta, drug eruption, cutaneous t-cell lymphoma, and ulcerating vasculitiserror! bookmark not defined.,6. lues maligna can be differentiated using the clinical presentation, serological syphilis testing, histologic correlation, jarischdiscussion skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 104 herxheimer reaction, and a response to treatment.error! bookmark not defined. the gold standard treatment for lues maligna is a single intramuscular dose of benzathine penicillin g 2.4 million units.7 in cases where the patient is allergic to penicillin, ceftriaxone can be used as an alternative.7 ulcers respond more slowly than other stages of lues maligna; however, most patients respond completely to therapy within 2 weeks to 4 months.i conflict of interest disclosures: none. funding: none. corresponding author: carly dunn baylor dermatology clinic houston, tx 77030 email: carlyd@bcm.edu references: 1. watson kmt, white jml, salisbury jr, creamer d. lues maligna. clin exp dermatol. 2004;29(6):625-627. doi:10.1111/j.13652230.2004.01630.x. 2. chang wt, hsieh tt, wu yh. malignant syphilis in human immunodeficiency virus-infected patients. derm sinica. 2015;33:21-25. 3. pföhler c, koerner r, von müller l, vogt t, müller csl. lues maligna in a patient with unknown hiv infection. bmj case rep. 2011;2011:bcr0520114221. doi:10.1136/bcr.05.2011.4221. 4. stevenson j, heath m. syphilis and hiv infection: an update. dermatol clin. 2006;24:497-507. 5. schöfer h, imhof m, thoma-greber e, et al. active syphilis in hiv infection: a multicentre retrospective survey. genitourin med. 1996;72:176-81. 6. romero-jimenez mj, suarez lozano i, fajardo pico jm, baron franco b. malignant syphilis in patient with human immunodeficiency virus (hiv): case report and literature review. an med interna. 2003;20(7):373–6 [in spanish]. 7. maldonado p, sendagorta cudos e, zamora vargas fx, merino mj, pinto ph. pathologically confirmed malignant syphilis using immunohistochemical staining: report of 3 cases and review of literature. sex transm dis. 2014;41:9497. 8. witkowski ja, parish lc. the great imitator: malignant syphilis with hepatitis. clin dermatol. 2002;20(2):156-163. doi:10.1016/s0738-081x(01)00249-8. 9. yamashita m, fujii y, ozaki k, et al. human immunodeficiency viruspositive secondary syphilis mimicking cutaneous t-cell lymphoma. diagn pathol. 2015;10(1). doi:10.1186/s13000-015-0419-5. 10. stary, a, stary, g. sexually transmitted infections. dermatology, by jean l. bolognia et al., elsevier, 2018, pp. 1447–1469. 11. sands m, markus a. lues maligna, or ulceronodular syphilis, in a man infected with human immunodeficiency virus: case report and review. clin infect dis. 1995;20:387-390. mailto:carlyd@bcm.edu 1school of medicine, baylor college of medicine, houston, texas 2baylor college of medicine, department of dermatology, houston, texas pasi changes in dose adjusters • patients who dose reduced to czp 200 mg q2w (n=33) achieved at least 75.9% improvement from baseline pasi at the time of first dose adjustment (table 2). – 19/33 (57.6%) of whom showed 100% improvement from baseline pasi at the time of first dose adjustment. • following the first dose reduction, 9/33 (27.3%) patients lost pasi 75 response and returned to czp 400 mg q2w (figure 2). – 7/9 (77.8%) of these dose re-adjusters regained pasi 75 within 12 weeks of returning to czp 400 mg q2w (figure 2). – 2/9 (22.2%) dose re-adjusters reduced their dose again from 400 mg to 200 mg q2w (figure 2). conclusions among patients in the czp 400 mg q2w escape arm, the majority of patients did not dose adjust and remained stable on czp 400 mg q2w throughout weeks 48–144. in most patients who reduced the dose to czp 200 mg q2w and lost response, their response was regained with return to the 400 mg q2w dose. the small sample size of this population is a limitation of these analyses, and these data should be interpreted with caution. synopsisobjective to assess psoriasis area and severity index (pasi) at the time of, and following, dose adjustment in the open-label extension period of three phase 3 clinical trials of certolizumab pegol in psoriasis. background • plaque psoriasis (pso) is an immune-mediated, inflammatory disease that affects 2−4% of adults.1 • certolizumab pegol (czp), an fc-free, pegylated anti-tumor necrosis factor biologic, has demonstrated efficacy and safety in moderate to severe pso.2,3 • here, we report patterns of dose adjustment between czp 400 mg and 200 mg q2w, and changes from baseline pasi, in phase 3 trials. methods study design • data were pooled from the cimpasi-1 (nct02326298), cimpasi-2 (nct02326272), and cimpact (nct02346240) trials (figure 1). patient eligibility criteria have been reported previously.1,2 • patients who were randomized to placebo at week 0 and were pasi 50 non-responders after 16 weeks of placebo treatment entered the open-label escape arm (weeks 16–48), where they received czp 400 mg q2w. • at week 48, patients in the escape arm entered the open-label extension period, where dose adjustments were possible from weeks 48–132, per protocol (figure 1). statistical analysis • proportions of pasi 75 responders and median changes from baseline in pasi at the time of dose adjustments are presented. results patient population and baseline characteristics • 116 patients did not achieve pasi 50 after 16 weeks of placebo treatment and entered the open-label czp 400 mg q2w escape arm; baseline demographics are shown in table 1. pasi 75 response in dose non-adjusters • 97 patients entered the open-label extension at week 48, and the majority (66.0%; 64/97) remained on czp 400 mg q2w throughout the entire period (figure 2). • 68.8% (44/64) of these patients were pasi 75 responders at week 144 (figure 2). a. blauvelt,1 a.b. gottlieb,2 f. fierens,3 f. brock,4 s. wiegratz,5 h. sofen6 bmi: body mass index; bsa: body surface area; czp: certolizumab pegol; dlqi: dermatology life quality index; pasi: psoriasis area and severity index; pga: physician’s global assessment; psa: psoriatic arthritis; pso: plaque psoriasis; q2w: every two weeks. figure 1 study designs table 1 demographics and baseline characteristics of included patients aloading dose of czp 400 mg q2w at weeks 0, 2, and 4; bdose adjustments were mandatory in patients with <pasi 50 and at the investigator’s discretion in patients with pasi 50–74; patients who received 12 weeks’ czp 400 mg q2w could dose reduce at the investigator’s discretion if they achieved pasi 75, and were withdrawn if they did not achieve pasi 50. placebo → czp 400 mg q2w (n=116) age (years), mean ± sd 46.4 ± 12.6 male, n (%) 76 (65.5) caucasian, n (%) 108 (93.1) weight (kg), mean ± sd 94.0 ± 26.1 duration of pso (years), mean ± sd 17.7 ± 12.1 psa,a n (%) 19 (16.4) pasi, mean ± sd 18.8 ± 6.7 bsa (%), mean ± sd 23.2 ± 13.9 pga score, n (%) 3: moderate 81 (69.8) 4: severe 35 (30.2) dlqi total score, mean ± sd 12.9 ± 7.4 any prior systemic therapy use for pso, n (%) 87 (75.0) prior biologic use, n (%) 33 (28.4) anti-tnf 19 (16.4) anti-il-17 12 (10.3) anti-il-12/il-23 6 (5.2) first dose adjustment czp 400 mg → czp 200 mg q2w second dose adjustment czp 200 mg q2w → czp 400 mg median change from baseline at the time of dose adjustment (%) 100.0 58.1 min–max (%) 75.9–100.0 44.6–74.7 institutions: 1oregon medical research center, portland, or, usa; 2department of dermatology, icahn school of medicine at mount sinai, new york, ny, usa; 3ucb pharma, brussels, belgium; 4ucb pharma, slough, uk; 5ucb pharma, monheim, germany; 6david geffen school of medicine, university of california los angeles, los angeles, ca, usa presented at fall clinical dermatology conference 2020 | october 29–november 1 | las vegas, nv dose adjustment patterns in the open-label extension arms of three phase 3 trials of certolizumab pegol in psoriasis: cimpasi-1, cimpasi-2, and cimpact references: 1parisi r. et al. j invest dermatol 2013;133:377–85; 2gottlieb ab. et al. jaad 2018;79:302–14.e6; 3lebwohl m. et al. jaad 2018;79:266–76. author contributions: substantial contributions to study conception/design, or acquisition/analysis/interpretation of data: ab, abg, ff, fb, sw, hs; drafting of the publication, or revising it critically for important intellectual content: ab, abg, ff, fb, sw, hs; final approval of the publication: ab, abg, ff, fb, sw, hs. author disclosures: ab: served as a scientific adviser and/or clinical study investigator for abbvie, aclaris, almirall, arena, athenex, boehringer ingelheim, bristol-myers squibb, dermavant, dermira, eli lilly and company, forte, galderma, incyte, janssen, leo pharma, novartis, ortho, pfizer, rapt, regeneron, sandoz, sanofi genzyme, sun pharma, and ucb pharma, and as a paid speaker for abbvie. abg: received honoraria as an advisory board member and consultant for avotres therapeutics; beiersdorf; boehringer ingelheim; bristol-myers squibb co.; incyte; janssen; leo pharma; eli lilly; novartis; sun pharmaceutical industries, inc.; ucb; and xbiotech (only stock options which she has not used); and has received research/educational grants from boehringer ingelheim, incyte, janssen, novartis, ucb, and xbiotech, sun pharma. ff, fb, sw: employees of ucb pharma. hs: consulting fees from abbvie; amgen; boehringer ingelheim; celgene; dermira; janssen; eli lilly; medimmune; novartis; pfizer; sun pharma; ucb pharma; valeant. acknowledgements: this study was funded by ucb pharma. we thank the patients and their caregivers in addition to the investigators and their teams who contributed to this study. the authors acknowledge mylene serna, pharmd, ucb pharma, smyrna, ga, usa for publication coordination and jenna hebert, phd, costello medical, boston, ma, usa for medical writing and editorial assistance and the costello medical design team for design support. all costs associated with development of this poster were funded by ucb pharma in accordance with the good publication practice (gpp3) guidelines.apsa was self-reported. figure 2 dose adjustment during the open-label extension period patients included in this analysis were randomized to placebo at week 0 and entered the open-label czp 400 mg q2w escape arm at week 16. pasi 75 response is defined as at least 75% improvement from baseline pasi. missing responder rates were imputed using non-response imputation, except those reported following dose re-adjustment (observed case). table 2 percent improvement from baseline pasi at time of dose adjustment median percentage change from baseline was assessed during the open-label extension period at the time of the first dose reduction (czp 400 mg q2w down to czp 200 mg q2w) and at the time of the second dose adjustment (czp 200 mg q2w back up to czp 400 mg q2w). czp 400 mg q2w placebo q2w czp 200 mg q2w czp 400 mg q2w lda maintenance period initial treatment period (double-blinded) open-label extensionb 1:2:2 randomization cimpasi-1 and cimpasi-2 1:3:3:3 randomization cimpact 3212week 0 16 48 144 dose adjustments: mandatory placebo q2w czp 200 mg q2w czp 400 mg q2w lda etn 50 mg bw washout open-label escape czp 400 mg q2w <pasi 50 <pasi 50 <pasi 50 – withdrawn (weeks 32–144) czp 200 mg q2w <pasi 50 ≥pasi 50 <pasi 75 ≥pasi 75 at the investigator’s discretion week 16 48 czp 400 mg q2w escape arm 144 open-label extension period with possible dose adjustment c z p 2 0 0 m g q 2 w c z p 4 0 0 m g q 2 w n=116 n=97 n=9 n=1 n=7 n=64 ≥pasi 75 in 44/64 (68.8%) dose non-adjusters at week 144 7/9 (77.8%) dose re-adjusters regained pasi 75 within 12 weeks dose non-adjusters dose re-adjusters dose adjusters 9/33 (27.3%) dose adjusters lost pasi 75 and increased dose 33/97 (34.0%) achieved ≥pasi 75 and reduced dose n=33 n=24 n=1n=2 randomized to placebo at week 0 czp 400 mg q2w escape arm open-label extension with possible dose adjustments: czp 400 mg q2w czp 200 mg q2w non-adjusters: 68.8% were pasi 75 responders dose adjustment to 200 mg: 27.3% of patients lost pasi 75 dose re-adjustment to 400 mg: <pasi 50 77.8% of patients regained pasi 75 integrated efficacy of fmx101 4% topical minocycline foam for the treatment of moderate-to-severe acne vulgaris: analyses of efficacy in clinically relevant subgroups of patients james q. del rosso, do1, linda stein gold, md2, leon kircik, md3, andrew alexis, md4, seemal r. desai, md5,6, vassilis stakias, pharmd7, iain stuart, phd7 1jdr dermatology research/thomas dermatology, las vegas, nv; 2henry ford health system, detroit, mi; 3icahn school of medicine at mount sinai, new york, ny; 4mount sinai, new york, ny; 5innovative dermatology, plano, tx; 6department of dermatology, the university of texas southwestern medical center, dallas, tx; 7vyne therapeutics inc., bridgewater, nj introduction • acne vulgaris is a chronic, inflammatory skin disorder that affects most of the population at some point in their lifetime1 • oral minocycline and doxycycline are considered first-line therapy for the treatment of moderate-to-severe acne, but they are associated with potentially serious systemic side effects2 • fmx101 4% is the first stable, topical foam formulation of minocycline and has been fda-approved for the daily treatment of acne • the efficacy of fmx101 4% in treating acne has previously been demonstrated in 3 double-blind, vehicle-controlled, 12-week, phase 3 clinical trials (fx2014-04, fx2014-05, and fx2017-22)3-4 • objective: to provide an integrated summary of efficacy of fmx101 4% versus vehicle foam for a pooled population of ~2500 subjects and for predefined subgroups of subjects that differ according to baseline disease severity, sex, age, and race methods • the 3 pivotal phase 3 studies (fx2014-04, n=466; fx2014-05, n=495; and fx2017-22, n=1488) were randomized, double-blind comparisons of fmx101 4% to vehicle foam (figure 1) • data for the change in inflammatory lesions from baseline at weeks 3, 6, 9, and 12 were pooled for overall analysis and for analysis of predefined subgroups that were separated by baseline disease severity (moderate, iga=3, or severe, iga=4), sex (male or female), age group (9-17 or ≥18 years) and race (white or non-white) figure 1. study design week 6week 3 week 9 week 12baseline key inclusion criteria • males and nonpregnant females ≥9 years • moderate-to-severe acne (iga score of 3 or 4) • 20-50 inflammatory lesions (papules, pustules, and nodules) • 25-100 non-inflammatory lesions (open and closed comedones) • absolute change in the inflammatory lesion count at week 12 compared with baseline • absolute change in the inflammatory lesion count at weeks 3, 6, and 9 compared with baseline integrated efficacy population (n=2449) vehicle foam (n=1071) fmx101 4% (n=1378) included efficacy endpoints iga, investigator’s global assessment, based upon a 6-point scale in which 0=clear, 1=almost clear, 2=mild, 3=moderate, 4=severe, and 5=very severe. results baseline demographics and disease characteristics • baseline demographics and disease characteristics were similar across treatment groups (table 1) • overall, the majority of subjects were female (60.6%) and white (73.1%) with moderate baseline disease severity (85.0%) • similar proportions of the subjects were pediatric (9-17 years, 48.4%) or adult (≥18 years, 51.6%) table 1. baseline demographics and disease characteristics variable fmx101 4% (n=1378) vehicle foam (n=1071) overall (n=2449) age 9 to 17 years, n (%) 670 (48.6) 515 (48.1) 1185 (48.4) ≥18 years, n (%) 708 (51.4) 556 (51.9) 1264 (51.6) sex, n (%) male 553 (40.1) 411 (38.4) 964 (39.4) female 825 (59.9) 660 (61.6) 1485 (60.6) race, n (%) white 1006 (73.0) 784 (73.2) 1790 (73.1) non-white 372 (27.0) 287 (26.8) 659 (26.9) black or african american 283 (20.6) 213 (19.9) 496 (20.3) asian 54 (3.9) 46 (4.3) 100 (4.1) american indian or alaska native 1 (0.1) 3 (0.3) 4 (0.2) native hawaiian or other pacific islander 3 (0.2) 3 (0.3) 8 (0.3) more than one race 30 (2.2) 19 (1.8) 49 (2.0) inflammatory lesion count, mean (sd) 31.2 (8.65) 31.1 (8.31) 31.2 (8.50) iga score, n (%) 3 – moderate 1171 (85.0) 911 (85.1) 2082 (85.0) 4 – severe 207 (15.0) 160 (14.9) 367 (15.0) iga, investigator’s global assessment. efficacy of fmx101 4% in the pooled population • overall, in the combined analysis of the 3 pivotal phase 3 studies, fmx101 4% demonstrated statistically significant benefit compared with vehicle foam – fmx101 4% demonstrated a significantly greater reduction from baseline in inflammatory lesions at week 12 than vehicle foam (figure 2a) – statistically significant advantages of fmx101 4% over vehicle foam were observed as early as week 3, and were sustained throughout the treatment period (figure 2b) figure 2. absolute reduction from baseline in inflammatory lesions for the pooled population -16.0-16.0 -13.0 -13.0 -20 -15 -10 -5 0 0 3 6 9 12 a bs ol ut e ch an ge fr om b as el in e in in fla m m at or y le si on s week -20 -15 -10 -5 0 a bs ol ut e ch an ge fr om b as el in e at w ee k 12 in in fla m m at or y le si on s p<0.0001, lsm diff=3.43, ci=(2.40, 4.46) n=1378 n=1071 fmx101 4% a b vehicle foam p<0.0001 p<0.0001 p<0.0001 p<0.0001 fmx101 4% vehicle foam -16.0-16.0 -13.0 -13.0 -20 -15 -10 -5 0 0 3 6 9 12 a bs ol ut e ch an ge fr om b as el in e in in fla m m at or y le si on s week -20 -15 -10 -5 0 a bs ol ut e ch an ge fr om b as el in e at w ee k 12 in in fla m m at or y le si on s p<0.0001, lsm diff=3.43, ci=(2.40, 4.46) n=1378 n=1071 fmx101 4% a b vehicle foam p<0.0001 p<0.0001 p<0.0001 p<0.0001 fmx101 4% vehicle foam lsm diff, least squares mean difference; ci, confidence interval; itt population with multiple imputation; p values are based on lsm diff from ancova. reduction in inflammatory lesions by baseline disease severity • fmx101 4% demonstrated a statistically significant advantage over vehicle foam at week 12, irrespective of baseline disease severity (figure 3a) • in the fmx101 4% group, there was a significantly greater reduction in inflammatory lesions from baseline compared with vehicle as early as week 3 that was maintained throughout treatment in both moderate (figure 3b) and severe (figure 3c) subgroups figure 3. efficacy of fmx101 4% across baseline disease severities -16.0 -15.4 -19.1 -13.0 -12.7 -14.8 -20 -15 -10 -5 0 pooled mod (iga=3) sev (iga=4) a bs ol ut e ch an ge fr om ba se lin e at w ee k 12 in in fla m m at or y le si on s p<0.0001 p<0.0001 1171 911 207 160n= 1378 1071 p<0.0001 30.2 29.9 37.0 37.9baseline lesion count:a a bs ol ut e ch an ge fr om b as el in e in in fla m m at or y le si on s b p<0.0001 -15.4 -12.7 -20 -15 -10 -5 0 0 3 6 9 12 p<0.0001 p<0.0001 p<0.0001 p<0.0001 week p<0.0001 fmx101 4% (n=1171) vehicle foam (n=911) moderate (iga=3) subgroup -19.1 -14.8 -20 -15 -10 -5 0 0 3 6 9 12 a bs ol ut e ch an ge fr om b as el in e in in fla m m at or y le si on s p<0.0001 p<0.0001 week c fmx101 4% (n=207) vehicle foam (n=160) severe (iga=4) subgroup fmx101 4% vehicle foam -16.0 -15.4 -19.1 -13.0 -12.7 -14.8 -20 -15 -10 -5 0 pooled mod (iga=3) sev (iga=4) a bs ol ut e ch an ge fr om ba se lin e at w ee k 12 in in fla m m at or y le si on s p<0.0001 p<0.0001 1171 911 207 160n= 1378 1071 p<0.0001 30.2 29.9 37.0 37.9baseline lesion count:a a bs ol ut e ch an ge fr om b as el in e in in fla m m at or y le si on s b p<0.0001 -15.4 -12.7 -20 -15 -10 -5 0 0 3 6 9 12 p<0.0001 p<0.0001 p<0.0001 p<0.0001 week p<0.0001 fmx101 4% (n=1171) vehicle foam (n=911) moderate (iga=3) subgroup -19.1 -14.8 -20 -15 -10 -5 0 0 3 6 9 12 a bs ol ut e ch an ge fr om b as el in e in in fla m m at or y le si on s p<0.0001 p<0.0001 week c fmx101 4% (n=207) vehicle foam (n=160) severe (iga=4) subgroup fmx101 4% vehicle foam mod, moderate; sev, severe; itt population with mi; p values are based on lsm difference from ancova. reduction in inflammatory lesions by sex • in both male and female subpopulations, fmx101 4% exhibited significantly greater reductions in inflammatory lesions at week 12 compared with vehicle foam (figure 4a) • the time course of efficacy of fmx101 4% over vehicle foam was comparable between sexes, with statistically significant advantages of fmx101 4% over vehicle observed at week 3 and maintained throughout study treatment (figure 4b-c) figure 4. reduction in inflammatory lesions for sex subgroups -16.0 -15.3 -16.5 -13.0 -12.9 -13.1 -20 -15 -10 -5 0 pooled male female a bs ol ut e ch an ge fr om ba se lin e at w ee k 12 in in fla m m at or y le si on s p<0.0001 p<0.0001 553 411 825 660n= 1378 1071 p<0.0001 32.8 32.8 30.1 30.1baseline lesion count:a p<0.0001 -15.3 -12.9 -20 -15 -10 -5 0 0 3 6 9 12 a bs ol ut e ch an ge fr om b as el in e in in fla m m at or y le si on s p<0.0001 p<0.0001 p<0.0001 p=0.0001 week b p<0.0001 fmx101 4% (n=553) vehicle foam (n=411) male subgroup -16.5 -13.1 -20 -15 -10 -5 0 0 3 6 9 12 a bs ol ut e ch an ge fr om b as el in e in in fla m m at or y le si on s p<0.0001 p<0.0001 week c fmx101 4% (n=825) vehicle foam (n=660) female subgroup fmx101 4% vehicle foam -16.0 -15.4 -19.1 -13.0 -12.7 -14.8 -20 -15 -10 -5 0 pooled mod (iga=3) sev (iga=4) a bs ol ut e ch an ge fr om ba se lin e at w ee k 12 in in fla m m at or y le si on s p<0.0001 p<0.0001 1171 911 207 160n= 1378 1071 p<0.0001 30.2 29.9 37.0 37.9baseline lesion count:a a bs ol ut e ch an ge fr om b as el in e in in fla m m at or y le si on s b p<0.0001 -15.4 -12.7 -20 -15 -10 -5 0 0 3 6 9 12 p<0.0001 p<0.0001 p<0.0001 p<0.0001 week p<0.0001 fmx101 4% (n=1171) vehicle foam (n=911) moderate (iga=3) subgroup -19.1 -14.8 -20 -15 -10 -5 0 0 3 6 9 12 a bs ol ut e ch an ge fr om b as el in e in in fla m m at or y le si on s p<0.0001 p<0.0001 week c fmx101 4% (n=207) vehicle foam (n=160) severe (iga=4) subgroup fmx101 4% vehicle foam -16.0 -15.3 -16.5 -13.0 -12.9 -13.1 -20 -15 -10 -5 0 pooled male female a bs ol ut e ch an ge fr om ba se lin e at w ee k 12 in in fla m m at or y le si on s p<0.0001 p<0.0001 553 411 825 660n= 1378 1071 p<0.0001 32.8 32.8 30.1 30.1baseline lesion count:a p<0.0001 -15.3 -12.9 -20 -15 -10 -5 0 0 3 6 9 12 a bs ol ut e ch an ge fr om b as el in e in in fla m m at or y le si on s p<0.0001 p<0.0001 p<0.0001 p=0.0001 week b p<0.0001 fmx101 4% (n=553) vehicle foam (n=411) male subgroup -16.5 -13.1 -20 -15 -10 -5 0 0 3 6 9 12 a bs ol ut e ch an ge fr om b as el in e in in fla m m at or y le si on s p<0.0001 p<0.0001 week c fmx101 4% (n=825) vehicle foam (n=660) female subgroup fmx101 4% vehicle foam itt population with mi; p values are based on lsm difference from ancova. reduction in inflammatory lesions by age • fmx101 4% exhibited significantly greater reductions in inflammatory lesions at week 12 compared with vehicle foam regardless of age subgroup (figure 5a) • the time course of efficacy of fmx101 4% over vehicle foam was comparable between pediatric (<18 years old) vs adults (≥18 years old), with statistically significant advantages of fmx101 4% over vehicle observed at week 3 and maintained throughout study treatment (figure 5b-c) figure 5. reduction in inflammatory lesions for age subgroups -16.0 -15.0 -17.0 -13.0 -11.4 -14.7 -20 -15 -10 -5 0 pooled 9-17 years ≥18 years a bs ol ut e ch an ge fr om ba se lin e at w ee k 12 in in fla m m at or y le si on s p<0.0001 p<0.0001 672 515 706 556n= 1378 1071 p<0.0001 32.1 32.5 30.4 29.9baseline lesion count:a p<0.0001 -15.0 -11.4 -20 -15 -10 -5 0 0 3 6 9 12 a bs ol ut e ch an ge fr om b as el in e in in fla m m at or y le si on s p<0.0001 p<0.0001 p<0.0001 p<0.0001 week b p<0.0001 fmx101 4% (n=672) vehicle foam (n=515) 9-17 years -17.0 -14.7 -20 -15 -10 -5 0 0 3 6 9 12 a bs ol ut e ch an ge fr om b as el in e in in fla m m at or y le si on s p<0.0001 p<0.0001 week c fmx101 4% (n=706) vehicle foam (n=556) ≥18 years fmx101 4% vehicle foam -16.0 -15.4 -19.1 -13.0 -12.7 -14.8 -20 -15 -10 -5 0 pooled mod (iga=3) sev (iga=4) a bs ol ut e ch an ge fr om ba se lin e at w ee k 12 in in fla m m at or y le si on s p<0.0001 p<0.0001 1171 911 207 160n= 1378 1071 p<0.0001 30.2 29.9 37.0 37.9baseline lesion count:a a bs ol ut e ch an ge fr om b as el in e in in fla m m at or y le si on s b p<0.0001 -15.4 -12.7 -20 -15 -10 -5 0 0 3 6 9 12 p<0.0001 p<0.0001 p<0.0001 p<0.0001 week p<0.0001 fmx101 4% (n=1171) vehicle foam (n=911) moderate (iga=3) subgroup -19.1 -14.8 -20 -15 -10 -5 0 0 3 6 9 12 a bs ol ut e ch an ge fr om b as el in e in in fla m m at or y le si on s p<0.0001 p<0.0001 week c fmx101 4% (n=207) vehicle foam (n=160) severe (iga=4) subgroup fmx101 4% vehicle foam -16.0 -15.0 -17.0 -13.0 -11.4 -14.7 -20 -15 -10 -5 0 pooled 9-17 years ≥18 years a bs ol ut e ch an ge fr om ba se lin e at w ee k 12 in in fla m m at or y le si on s p<0.0001 p<0.0001 672 515 706 556n= 1378 1071 p<0.0001 32.1 32.5 30.4 29.9baseline lesion count:a p<0.0001 -15.0 -11.4 -20 -15 -10 -5 0 0 3 6 9 12 a bs ol ut e ch an ge fr om b as el in e in in fla m m at or y le si on s p<0.0001 p<0.0001 p<0.0001 p<0.0001 week b p<0.0001 fmx101 4% (n=672) vehicle foam (n=515) 9-17 years -17.0 -14.7 -20 -15 -10 -5 0 0 3 6 9 12 a bs ol ut e ch an ge fr om b as el in e in in fla m m at or y le si on s p<0.0001 p<0.0001 week c fmx101 4% (n=706) vehicle foam (n=556) ≥18 years fmx101 4% vehicle foam itt population with mi; p values are based on lsm difference from ancova. reduction in inflammatory lesions by race • in both white and non-white subjects, fmx101 4% exhibited significantly greater reductions in inflammatory lesions at week 12 compared with vehicle foam (figure 6a) • statistically significant advantages of fmx101 4% over vehicle foam were observed as early as week 3, and were sustained throughout the treatment period for both white (figure 6b) and non-white (figure 6c) subgroups figure 6. reduction in inflammatory lesions for race subgroups -16.0 -16.0 -16.0 -13.0 -12.6 -14.1 -20 -15 -10 -5 0 pooled white non-white a bs ol ut e ch an ge fr om ba se lin e at w ee k 12 in in fla m m at or y le si on s p<0.0001 p=0.0048 1006 784 372 287n= 1378 1071 p<0.0001 31.7 31.5 29.8 30.1baseline lesion count:a p=0.0048 -16.0 -12.6 -20 -15 -10 -5 0 0 3 6 9 12 a bs ol ut e ch an ge fr om b as el in e in in fla m m at or y le si on s p<0.0001 p<0.0001 p<0.0001 p<0.0001 week b p=0.0001 fmx101 4% (n=1006) vehicle foam (n=784) white subgroup -16.0 -14.1 -20 -15 -10 -5 0 0 3 6 9 12 a bs ol ut e ch an ge fr om b as el in e in in fla m m at or y le si on s p=0.0001 p<0.0001 week c fmx101 4% (n=372) vehicle foam (n=287) non-white subgroup fmx101 4% vehicle foam -16.0 -15.0 -17.0 -13.0 -11.4 -14.7 -20 -15 -10 -5 0 pooled 9-17 years ≥18 years a bs ol ut e ch an ge fr om ba se lin e at w ee k 12 in in fla m m at or y le si on s p<0.0001 p<0.0001 672 515 706 556n= 1378 1071 p<0.0001 32.1 32.5 30.4 29.9baseline lesion count:a p<0.0001 -15.0 -11.4 -20 -15 -10 -5 0 0 3 6 9 12 a bs ol ut e ch an ge fr om b as el in e in in fla m m at or y le si on s p<0.0001 p<0.0001 p<0.0001 p<0.0001 week b p<0.0001 fmx101 4% (n=672) vehicle foam (n=515) 9-17 years -17.0 -14.7 -20 -15 -10 -5 0 0 3 6 9 12 a bs ol ut e ch an ge fr om b as el in e in in fla m m at or y le si on s p<0.0001 p<0.0001 week c fmx101 4% (n=706) vehicle foam (n=556) ≥18 years fmx101 4% vehicle foam -16.0 -15.4 -19.1 -13.0 -12.7 -14.8 -20 -15 -10 -5 0 pooled mod (iga=3) sev (iga=4) a bs ol ut e ch an ge fr om ba se lin e at w ee k 12 in in fla m m at or y le si on s p<0.0001 p<0.0001 1171 911 207 160n= 1378 1071 p<0.0001 30.2 29.9 37.0 37.9baseline lesion count:a a bs ol ut e ch an ge fr om b as el in e in in fla m m at or y le si on s b p<0.0001 -15.4 -12.7 -20 -15 -10 -5 0 0 3 6 9 12 p<0.0001 p<0.0001 p<0.0001 p<0.0001 week p<0.0001 fmx101 4% (n=1171) vehicle foam (n=911) moderate (iga=3) subgroup -19.1 -14.8 -20 -15 -10 -5 0 0 3 6 9 12 a bs ol ut e ch an ge fr om b as el in e in in fla m m at or y le si on s p<0.0001 p<0.0001 week c fmx101 4% (n=207) vehicle foam (n=160) severe (iga=4) subgroup fmx101 4% vehicle foam -16.0 -16.0 -16.0 -13.0 -12.6 -14.1 -20 -15 -10 -5 0 pooled white non-white a bs ol ut e ch an ge fr om ba se lin e at w ee k 12 in in fla m m at or y le si on s p<0.0001 p=0.0048 1006 784 372 287n= 1378 1071 p<0.0001 31.7 31.5 29.8 30.1baseline lesion count:a p=0.0048 -16.0 -12.6 -20 -15 -10 -5 0 0 3 6 9 12 a bs ol ut e ch an ge fr om b as el in e in in fla m m at or y le si on s p<0.0001 p<0.0001 p<0.0001 p<0.0001 week b p=0.0001 fmx101 4% (n=1006) vehicle foam (n=784) white subgroup -16.0 -14.1 -20 -15 -10 -5 0 0 3 6 9 12 a bs ol ut e ch an ge fr om b as el in e in in fla m m at or y le si on s p=0.0001 p<0.0001 week c fmx101 4% (n=372) vehicle foam (n=287) non-white subgroup fmx101 4% vehicle foam itt population with mi; p values are based on lsm difference from ancova. summary • fmx101 4% demonstrated efficacy over vehicle foam in treating moderate-to-severe acne vulgaris in a pooled population of ~2500 subjects from 3 phase 3 studies – overall, the fmx101 4% group exhibited a significantly greater reduction in inflammatory lesions from baseline at week 12 compared with the vehicle group – efficacy of fmx101 4% over vehicle foam was observed as early as week 3, and continued throughout the 12-week treatment period • analyses were performed on the integrated data set to characterize the efficacy of fmx101 4% in treating acne in predefined subgroups of subjects – consistent with results from the pooled population, fmx101 4% resulted in significantly greater reductions in inflammatory lesions at all assessed timepoints in subgroups of subjects that were separated by baseline disease severity, sex, age, and race conclusions • fmx101 4% demonstrated statistically significant differences compared with vehicle in the reduction of inflammatory lesions from baseline at weeks 3, 6, 9, and 12 in a pooled population of 3 phase 3 studies, as well as in predefined subgroups of subjects • these data suggest that fmx101 4% appears to be effective for the treatment of acne in a wide variety of patients, whether male or female, adult or pediatric, white or non-white, and with moderate or severe disease at baseline disclosures/acknowledgment disclosures dr. del rosso is a consultant for aclaris, almirall, athenex, cutanea, dermira, ferndale, galderma, genentech, leo pharma, menlo, novan, ortho, pfizer, promius, sanofi/regeneron, skinfix, and sunpharma; he has received research support from aclaris, almirall, athenex, botanix, celgene, cutanea, dermira, galderma, genentech, leo pharma, menlo, novan, ortho, promius, regeneron, sunpharma, and thync; he receives honoraria from aclaris, celgene, galderma, genentech, leo pharma, novartis, ortho, pfizer, promius, sanofi/regeneron, and sunpharma; and he participates in speakers bureaus for honoraria from aclaris, celgene, galderma, genentech, leo pharma, novartis, ortho, pfizer, promius, sanofi/regeneron, and sunpharm. dr. stein gold is an advisor and investigator for foamix pharmaceuticals inc, galderma, leo pharma, novartis, and valeant and is an investigator for janssen, abbvie, and solgel. dr. kircik is an investigator and consultant for foamix pharmaceuticals. dr. alexis is a consultant for beiersdorf, bausch health, bristol myers-squibb, celgene, dermavent, foamix, galderma, leo pharma, l’oreal, menlo, novartis, pfizer, sanofi-regeneron, scientis, ucb, unilever, and valeant; he reports grants and/or research support from almirall, bristol myers-squibb, cara therapeutics, celgene, galderma, leo pharma, menlo, novartis, and valeant (bausch health). dr. desai is an investigator for dermavant, abbvie, novan, and symbio and a consultant for pfizer, foamix, galderma, scientis, dermira, and verrica. drs. stakias and stuart are employees and stockholders at vyne therapeutics inc. acknowledgment editorial support was provided by scient healthcare communications. references 1. thiboutot dm, dreno b, abanmi a, et al. practical management of acne for clinicians: an international consensus from the global alliance to improve outcomes in acne. j am acad dermatol. 2018;78(2s1):s1-s23. 2. zaenglein al, pathy al, schlosser bj, et al. guidelines of care for the management of acne vulgaris. j am acad dermatol. 2016;74(5)945-973. 3. gold ls, dhawan s, weiss j, et al. a novel topical minocycline foam for the treatment of moderate-to-severe acne vulgaris: results of 2 randomized, double-blind, phase 3 studies. j am acad dermatol. 2019; 80(1):168-177. 4. raoof tj, hooper d, moore a, et al. efficacy and safety of a novel topical minocycline foam for the treatment of moderate-to-severe acne vulgaris: a phase 3 study. j am acad dermatol. 2020;82(4):832-837. funding this study was funded by foamix pharmaceuticals ltd, a wholly owned subsidiary of vyne therapeutics inc. acknowledgements study funded by galderma r&d, llc. medical writing supported by galderma laboratories, l.p. alt.p-rd18250-08 introduction introduction to trifarotene 50 μg/g cream:1 • retinoid receptor agonist that selectively targets retinoic acid receptor gamma • low systemic exposure after topical administration • once-daily cream developed for treatment of acne vulgaris on the face and trunk objectives: • study 1 and study 2: assess safety and efficacy of trifarotene 50 μg/g cream applied once daily for 12 weeks in subjects with acne vulgaris • long-term safety and efficacy study: evaluate long-term safety and efficacy of trifarotene 50 μg/g cream use over a period of 52 weeks trifarotene 50 μg/g cream for treatment of acne vulgaris – a summary of two randomized trials and a long-term safety study jerry tan, md1; james del rosso, do2; jonathan weiss, md3; linda stein gold, md4; fran cook-bolden, md5; lawrence eichenfield, md6; emil tanghetti, md7; michael graeber, md8; allesandra alió saenz, md8; faiz ahmad8 1department of medicine, university of western ontario, windsor on, canada, 2jdr dermatology research/thomas dermatology, las vegas, nv; 3gwinnett dermatology, snellville, ga; 4henry ford medical center department of dermatology, detroit, mi; 5mount sinai hospital, new york, ny; 6department of pediatric and adolescent dermatology, rady children’s hospital, university of california, san diego, ca; 7center for dermatology and laser surgery sacramento, ca; 8galderma r&d, llc, fort worth, tx methods study 1 and 2 • two identical multi-center, double-blind, randomized 12-week studies of subjects with moderate facial and truncal acne comparing vehicle with once-daily trifarotene 50 μg/g cream; n = 2,420 • study 1: conducted at 109 sites, majority united states • study 2: conducted at 80 sites, majority europe • primary efficacy endpoints (face) measured at baseline and weeks 1, 2, 4, 8, and 12: success rate: percentage of subjects with investigator global assessment (iga) of clear (0) or almost clear (1) and at least a 2-grade improvement absolute change in facial inflammatory/non-inflammatory lesion count • secondary efficacy endpoints (trunk) measured at baseline and weeks 1, 2, 4, 8, and 12: success rate: percentage of subjects with physician global assessment (pga) of clear (0) or almost clear (1) and at least a 2-grade improvement absolute change in truncal inflammatory/non-inflammatory lesion count • safety endpoints: incidence of adverse events and local tolerability1 long-term efficacy and safety study • a long-term safety and efficacy study conducted over 52 weeks for once-daily use of trifarotene 50 μg/g cream in patients with moderate facial and truncal acne; n = 455 • efficacy and tolerability measured at baseline and weeks 12, 20, 26, 38, and 52 • primary endpoints (safety) included: local tolerability (erythema, scaling, dryness, stinging/burning) on face and trunk adverse events • secondary endpoints (efficacy) included: success rate: iga/pga score of clear (0) or almost clear (1) and at least a 2-grade iga/pga improvement from baseline grade change from baseline of iga and pga subject’s assessment of facial acne improvement2 results study 1 and 2 efficacy: results of all efficacy assessments at week 12 significant (p <.001) in favor of trifarotene 50 μg/g cream versus vehicle • study 1: primary efficacy endpoints (mi) 29.4% iga success rate in trifarotene 50 μg/g cream compared with 19.5% for vehicle mean percent change of -54.4% in facial inflammatory lesion count from baseline to week 12 for trifarotene 50 μg/g cream, compared with -44.8% for vehicle mean percent change of -49.7% in facial non-inflammatory lesion count from baseline to week 12 for trifarotene 50 μg/g cream, compared with -35.7% for vehicle (multiple imputation values used) • study 2: primary efficacy endpoints 42.3% trifarotene 50 μg/g cream iga success rate compared with 25.7% for vehicle mean percent change of -66.2% in facial inflammatory lesion count from baseline to week 12 for trifarotene 50 μg/g cream, compared with -51.2% for vehicle mean percent change of -57.7% in facial non-inflammatory lesion count from baseline to week 12 for trifarotene 50 μg/g cream, compared with -43.9% for vehicle (multiple imputation values used) safety: • skin irritation related to trifarotene 50 μg/g cream was transient, and consistent with known patterns of topical retinoid dermatitis most common related aes included irritation, pruritus, and sunburn (incidence ≥1%) severe aes related to trifarotene 50 μg/g cream reported in nine subjects versus none in the vehicle group, with no serious aes reported severe related aes led to subject discontinuation in 1.9% of the trifarotene 50 μg/g cream group in study 1, and in 1.2% of the trifarotene 50 μg/g cream group in study 2 • tolerability signs related to trifarotene 50 μg/g cream assessed as mostly mild to moderate by investigator long-term efficacy and safety study efficacy: • both iga and pga success rates improved over time iga success rates increased from 26.6% at week 12 to 65.1% at week 52 pga success rates increased from 38.6% at week 12 to 66.9% at week 52 at week 52, 57.9% of patients had both iga and pga success2 safety: • majority of treatment emergent adverse events (teaes) occurred during the first three months of the study • most common teaes included pruritus, irritation, and sunburn • no serious teaes were related to trifarotene 50 μg/g cream2 references we wish to thank our colleagues in galderma international, galderma r&d in sophia antipolis, and galderma laboratories and the trifarotene study group, as well as all investigators in the united states, canada, europe, and russia who participated in these clinical trials. 1. tan j, thiboutot d, popp g, gooderham m, lynde c, del rosso j, et al. randomized phase 3 evaluation of trifarotene 50 mg/g cream treatment of moderate facial and truncal acne. j am acad dermatol. 2019;80:1691-9. 2. blume-peytavi u, fowler j, lajos k, draelos z, cook-bolden f, dirschka t, et al. long-term safety and efficacy of trifarotene 50μg/g cream, a first-inclass rar-γ selective topical retinoid, in patients with moderate facial and truncal acne. j eur acad dermatol venereol. 2019:(in preparation). summary • in study 1 and study 2, trifarotene 50 μg/g cream had a rapid effect, with significant reduction in lesion counts on the face as early as week 1, and on the trunk as early as week 2 • subjects in the long-term safety and efficacy study demonstrated continuous clinical improvement over the course of the 52-week study period • trifarotene 50 μg/g cream is well tolerated and efficacious for treatment of facial and truncal acne, compared with vehicle • treatment with trifarotene 50 μg/g cream was observed to be safe and tolerable in both the 12and 52-week studies1, 2 subject screened n = 2817 subject randomized n = 2420 screen failure n = 397 discontinued n = 98 discontinued n = 116 r trifarotene 50 µg cream n = 1214 completed study protocol n = 1098 vehicle n = 1206 completed study protocol n = 1108 study 1 study 2 mean age (standard deviation): 19.4 ± 6.41 gender ratio: 52.1% female/47.9% male mean age (standard deviation): 19.7 ± 6.3 gender ratio: 57.3% female/42.7% male figure 2. efficacy comparison of trifarotene 50 μg/g cream and vehicle 0.5% 1.8% 4.0% 9.5% 20.0% 19.5% 0.2% 2.2% 7.9%* 16.2%* 29.7%* 29.4% † 0 5 10 15 20 25 30 35 40 45 50 baseline *p<.05; 95% ci (1.2, 6.7) ; † treatment difference at week 12 (95% ci) 9.9% (4.8, 14.8); p<.001 1 2 4 8 12 12 (mi) ig a su cce ss % weeks vehicle trifarotene 50 µg/g *p<.05; 95% ci (4.6, 13.7) ; † treatment difference (95% ci) 10.7% (5.4, 16.1); p<.001 pg a su cce ss % 0 5 10 15 20 25 30 35 40 45 50 baseline 1 2 4 8 12 12 (mi) weeks vehicle trifarotene 50 µg/g 0.7% 4.5% 0.5% 8.2% 14.4% 25.7% 25.0% 3.2% 11.2% 23.3%* 35.8%* 35.7%† study 1 face study 2 face ig a su cce ss % weeks 0 5 10 15 20 25 30 35 40 45 50 baseline *p<.05; 95% ci (5.8, 14.1) ; † treatment difference at week 12 (95% ci) 16.6% (11.3, 22.0); p<.001 1 2 4 8 12 12 (mi) vehicle trifarotene 50 µg/g 0.7% 1.8% 3.9% 10.6% 25.8% 25.7% 0.5% 3.1% 5.6% 20.7%* 42.8%* 42.3%† pg a su cce ss % weeks *p<.05; 95% ci (5.8, 14.1) ; † treatment difference at week 12 (95% ci) 16.6% (11.3, 22.0); p<.001 0 5 10 15 20 25 30 35 40 45 50 baseline 1 2 4 8 12 12 (mi) vehicle trifarotene 50 µg/g 0.7% 3.0% 5.7% 14.4% 30.1% 29.9% 1.3% 4.1% 8.6% 22.4%* 43.1%* 42.6%† study 1 trunk study 2 trunk figure 3. study 1 and study 2 safety data (score is a 3-point scale) study 1 face study 2 trunk study 2 face study 1 trunk week 1 2 4 8 12 mild m ea n sc or e 1.25 1.50 1.00 0.75 0.50 0.25 0.00 dryness trifarotene 50 µg/g (n = 612) vehicle (n = 596) erythema stinging/burning scaling baseline final visit worst week m ea n sc or e 1 2 4 8 12 1.25 1.50 1.00 0.75 0.50 0.25 0.00 dryness trifarotene 50 µg/g (n = 612) vehicle (n = 596) erythema stinging/burning scaling mild baseline final visit worst m ea n sc or e 1 2 4 8 week 12 1.25 1.50 1.00 0.75 0.50 0.25 0.00 dryness trifarotene 50 µg/g (n = 612) vehicle (n = 596) erythema stinging/burning scaling mild baseline final visit worst mild m ea n sc or e week 1 2 4 8 12 mild 1.25 1.50 1.00 0.75 0.50 0.25 0.00 dryness trifarotene 50 µg/g (n = 612) vehicle (n = 596) erythema stinging/burning scaling baseline final visit worst m ea n sc or e 1.50 1.25 1.00 0.75 0.50 0.25 0.00 drynesserythema mild stinging/burningscaling weeks final visit worst baseline 1 2 4 8 12 20 26 38 52 m ea n sc or e 1.50 1.25 1.00 0.75 0.50 0.25 0.00 drynesserythema mild stinging/burningscaling weeks final visit worst baseline 1 2 4 8 12 20 26 38 52 severity scale score: 0 (none), 1 (mild), 2 (moderate), 3 (severe) face trunk subject screened n = 507 subject enrolled n = 455 screen failure n = 52 discontinued n = 2 discontinued n = 77 subject treated n = 453 completed 6 months of study protocol n = 376 discontinued n = 28 completed 12 months of study protocol n = 348 70 60 50 40 30 20 10 0 12 20 26 38 52 26.6 43.3 50.1 57.6 65.1 38.6 54.1 58.4 62.5 66.9 baseline su cce ss r at e (% ) weeks pga (trunk) iga (face) figure 5. iga/pga success rates from baseline to week 52 figure 4. long-term safety and efficacy study flowchart figure 1. study 1 and study 2 flowchart figure 6. local tolerability of trifarotene 50 µg/g cream skin november 2017 volume 1 issue 3 copyright 2017 the national society for cutaneous medicine 110 a view from the top interview with bill humphries, executive vice president (dermatology) of ortho dermatologics question: where do you think the field of dermatology is going and what needs to be done? humphries: i see previously underserved markets like psoriasis and atopic dermatitis being addressed by new and innovative medicines which improve patients’ lives. i see a continued commitment by large and small companies to improve current therapies and also advance treatment for unmet needs. the solo practitioner dermatologist that i grew up with in this industry is long gone we now see multi-physician groups, physician extenders and affiliations amongst the providers. patients are more educated and engaged in their treatment, creating a robust dialogue in the office. aesthetic treatments are continuously expanding and driving patient foot traffic this market is now hyper-competitive and the cash pay component is a driver for all parties. last but not least is the payer environment; dermatological medications are on the radar screen of the payers and the challenge of patients getting the brand that is prescribed for them a significant hurdle. on the horizon, i see the need for change in how patients and physicians have a predictable experience when it comes to brands that are prescribed. the status quo is not sustainable and in order to serve the specialty and the patients, this issue must be addressed. i see aesthetics continuing to grow, driven by patient desire, innovation and companies like allergan growing the markets. finally, i see significant innovation for medical dermatology and some of the unmet needs we have addressed with meaningful therapies for the patients who are suffering. abstract each issue, as part of our new “a view from the top” segment, we will be sitting down with a leader in the field of dermatology or in industry to discuss current trends in the specialty and pertinent challenges faced by physicians and patients. in this first edition of “a view from the top,” we speak with bill humphries, executive vice president of ortho dermatologics. mr. humphries offers insight into the current state of the specialty, the future direction of dermatology, the challenges of treating patients with chronic skin diseases, and how physician-industry collaboration can be utilized to improve patient access to medications. mr. humphries also provides words of advice for young physicians entering the specialty. skin november 2017 volume 1 issue 3 copyright 2017 the national society for cutaneous medicine 111 question: what are the challenges that are pertinent to patients with chronic skin diseases? humphries: it’s just that – these skin diseases are chronic and without a cure. getting patients to disease free days is the key and a drive to metrics like pasi 100, completely clear, is the new goal not only for psoriasis but for all skin diseases. yes, the goal is always to calm and treat but it is also to get to a cure. question: what are some of the current unmet needs within the field of dermatology? humphries: there are some obvious ones, like warts, hair and nails in terms of diseases. however, right now the biggest unmet need in my mind is the patient getting what the dermatologist prescribes. over the last 30 years what i have learned from many dermatologist friends is that dermatology is as much an art as it is a science. every patient is unique and different, they have different skin types, lifestyles and needs. while to some it seems frustrating to have so many vehicles for delivering topical medications, my view is that this approach is patient centric because a prescribed medication that is not used is a failure. question: what can be done about the cost of drugs in dermatology? humphries: i think there is a need for creative strategies around access. when dermatologists write prescriptions for treatments that they think will best treat that specific patient, that patient should be able to receive that medication. we’ve been working on this problem at ortho dermatologics and i am hopeful that we’ll be able to announce a few sustainable solutions soon. question: what words of advice would you have for someone who is starting their career in dermatology? humphries: i’d congratulate them and let them know that they have chosen a field that allows them to change people’s lives on many different levels – how they look, how they feel, how confident they are in approaching others. they are also joining an industry that supports one another, so i would encourage them to meet as many different dermatologists as they can, ask questions and form relationships that will help them as they establish their reputations and practices. finally, i would encourage them to take advantage of the spirit of philanthropy that exists in the industry – whether it’s through an industry program like our aspire higher or passion to heal programs or through the great work the societies do, this is an industry that believes in working towards the greater good. skin september 2017 volume 1 issue 2 copyright 2017 the national society for cutaneous medicine 107 compelling comments the importance of recognition of the skin cancer risk of native americans: a call to action ajay kailas b.s., a , james a. solomon, m.d., ph.d, a,b,c darrell s. rigel m.d. m.s, d eliot mostow, m.d., m.p.h, e amy j. mcmichael m.d., f ellen n. pritchett, m.d., m.p.h, g diane jacksonrichards, m.d., g seemal r. desai, m.d., h susan c. taylor, m.d. i university of central florida college of medicine, a ameriderm research b , university of illinois college of medicine c , department of dermatology at new york university d , department of dermatology at northeastern ohio medical university, e department of dermatology at wake forest university, f multicultural dermatology center, henry ford medical center g department of dermatology at university of texas southwestern school of medicine h , department of dermatology at university of pennsylvania i the term “skin of color” was created to be an all-encompassing term for those of ethnic origin who share similar characteristics and diseases related to skin pigmentation and scarring. however, most skin of color articles related to skin cancer focus solely on african-americans, hispanics, and asian populations 1-3 . native americans are consistently excluded from these studies 3 . as a result, details such as skin cancer knowledge, perceived risk, sunscreen use, and behavioral practices that are well known for other ethnicities are relatively unknown for this group 2,4 . without such data, even the most basic information regarding their skin cancer risk becomes difficult to ascertain. in fact, native americans are an important us demographic. surprisingly to some, 5.2 million americans trace all or a substantial part of their heritage to native american roots and this population is growing in every state except vermont 1 . for these reasons, it is becoming increasingly important for dermatologists to become more aware of their skin disease related needs. despite their lower incidence of melanoma, native americans also have a lower 5-year survival rate of 69.8% versus 91% among caucasians 5,6 . this may be due to a lower index of suspicion in these persons leading to delay in diagnosis and is particularly worrisome because the current data suggests that the incidence of this cancer is continuing to rise in this group. furthermore, the mean age for diagnosis of melanoma is abstract melanoma is a deadly skin cancer affecting a significant part of the u.s. population. people of color are more likely to face lower survival rates from melanoma and are likely to be diagnosed at a later stage. efforts to combat this have largely focused on asian, hispanic, and african american patients. native americans have been unfortunately excluded from such studies. this article is a call to action and is an effort to raise awareness for native american inclusion in future skin cancer studies so their skin cancer knowledge and risk can be appropriately ascertained. review skin september 2017 volume 1 issue 2 copyright 2017 the national society for cutaneous medicine 108 52-54, one of the lowest out of all races 1 . therefore, it is vital that native americans become aware of their skin cancer risks, use preventive measures such as sunscreen, are aware of the importance of early diagnosis, and are included in educational interventions to reduce their risk of skin cancer. yet despite this, skin of color articles that utilize direct interventions (such as focus groups or classes) in order to educate ethnic populations of skin cancer risk have also often excluded native americans 5 . none of five recent skin cancer interventions included such a participant. this is may be due, in part, to the cultural and language barriers faced when attempting to recruit them 1 . education is the primary method for increasing skin cancer knowledge among ethnic groups 3 . therefore, if these efforts exclude native americans, they may not be having broad-based impact across these groups. what can be done to ameliorate this problem? better data needs to be collected from this group to assess the knowledge gaps related to skin cancer both in patients and providers. to facilitate this effort, researchers should utilize translators and work together with community leaders to develop relationships based on trust and understanding. hopefully, efforts such as these will lead to an increased level of knowledge and understanding of the associated challenges and the generation of targeted public educational programs that will help reduce the risk of skin cancer in this underserved population. conflict of interest disclosures: none. funding: none. corresponding author: ajay kailas ucf college of medicine 6850 lake nona blvd. orlando, fl, 32827 email: ajay.kailas@knights.ucf.edu phone: 504-231-0091 references: 1.) kryatova m.s. and okoye g.a. dermatology in the north american indian/alaska native population. int j dermatology. 2016. 55(2):125-34. 2.) agbai o.n., buster k., sanchez m. et al. skin cancer and photoprotection in people of color: a review and recommendations for physicians and the public. journal of the am acad of dermatol. 2014. 70(4):748-62. 3.) clairwood m., ricketts j., grant-kels j., gonsalves l. melanoma in skin of color in connecticut: an analysis of melanoma incidence and stage at diagnosis in nonhispanic blacks, non-hispanic whites, and hispanics. international j of dermatology. 53(4)425-33. 4.) robinson j.k., joshi k.m., ortiz s., kundu v.r. melanoma knowledge, perception, and awareness in ethnic minorities in chicago: recommendations regarding education. psycho-oncology. 2013. 20:313-320 5.) cormier j.n., xing y., ding m., et al. ethnic differences among patients with cutaneous melanoma. arch intern med 2006;166:190714. 6.) siegel r.l., miller k.d., jemal a. cancer statistics, 2017. ca cancer j clin. 2017. 67(1):7-30. mailto:ajay.kailas@knights.ucf.edu presented at fall clinical dermatology conference for pas & nps; june 9-11, 2023; orlando, fl disclosures this study was sponsored by pfizer inc. r. wolk, s.h. zwillich, d. wajsbrot, h.m. ahmed, and l. takiya are employees of pfizer, inc and hold stock or stock options in pfizer, inc. m. senna: scientific advisory board for eli lilly, arena pharmaceuticals, pfizer, l’oreal. consulting for kintor, eli lilly, pfizer. speaker for eli lilly, pfizer. research funding from eli lilly, concert, clarity, and follica, leo pharma, santiste. board of directors for the scarring alopecia foundation and american hair research society. s. forman: no conflicts of interest to disclose. l. bordone: no disclosures or conflicts. p. cueva has participated as consultant, advisory board member, honorary for speaking and/or clinical trials with the following pharmaceutical companies: abbvie, almirall, amgen, astellas, biogen, boehringer-ingelheim, celgene, janssen., leo pharma, lilly, msd, novartis, pfizer, roche, sanofi and ucb. t third-party medical writing assistance, provided by health interactions, inc, was funded by pfizer inc. references 1. islam n, et al. autoimmun rev. 2015;14:81-89. 2. king b, et al. lancet 2023;401:1518-1529. copies of this e-poster obtained through qr, ar and/or text key codes are for personal use only and may not be reproduced without written permission of the authors https://scientificpubs.congressposter.com/p/ckmy8jnlmxv07zqm maryanne senna,1 seth forman,2 lindsey bordone,3 pablo de la cueva dobao,4 robert wolk,5 samuel h. zwillich,5 dalia wajsbrot,6 haytham mohamed ahmed,7 liza takiya8 1lahey hospital and medical center, burlington, ma, usa; 2 forcare medical center, tampa, fl, usa; 3columbia university medical center, ny, ny, usa; 4departamento de dermatología. hospital universitario infanta leonor, madrid, spain; 5pfizer inc, groton, ct, usa; 6pfizer inc, new york, ny, usa; 7pfizer inc, dubai, united arab emirates; 8pfizer inc, collegeville, pa, usa scalp, eyebrow, and eyelash hair regrowth with continued ritlecitinib treatment among patients with alopecia areata without target efficacy response at week 24: post hoc analysis of the allegro phase 2b/3 study background • alopecia areata (aa) is an autoimmune disease that has an underlying immuno-inflammatory pathogenesis and is characterized by nonscarring hair loss ranging from small patches to complete scalp, face, and/or body hair loss1 • ritlecitinib, an oral jak3/tec family kinase inhibitor, demonstrated efficacy and safety in patients aged ≥12 years with aa and ≥50% scalp hair loss in the allegro phase 2b/3 trial (nct03732807)2 significant improvements in the proportion of patients with severity of alopecia tool (salt) score ≤20 (≤20% of scalp without hair) and salt score ≤10 (≤10% of scalp without hair) at week 24 were observed in the 50 mg and 30 mg ritlecitinib treatment groups (± 200 mg loading dose) vs placebo objective • to assess response to ritlecitinib between weeks 28–48 among subpopulations of patients with aa who did not achieve target efficacy response criteria at week 24 methods study design • the allegro phase 2b/3 trial was a randomized, double-blind, placebo-controlled, combined dose-ranging and pivotal study (figure 1) figure 1. allegro-2b/3 study design rit 200 mg qd rit 200 mg qd rit 50 mg qd rit 30 mg qd rit 10 mg qd placebo placebo rit 50 mg qd rit 30 mg qd rit 50 mg qd rit 30 mg qd rit 10 mg qd placebo placebo rit 50 mg qd rit 30 mg qd rit 50 mg qd rit 30 mg qd rit 10 mg qd rit 200/50 mg qd rit 50 mg qd placebo-controlled (24 weeks) study week extension (24 weeks) maintenance (20 weeks) loading (4 weeks) bl 2 4 8 12 18 26 28 34 40 4824 s cr ee ni ng r an do m iz at io n screening and randomization (35 days) n=132 n=66 n=65 n=63 n=130 n=132 n=130 bl, baseline; qd, once daily; rit, ritlecitinib. no other therapies for aa were allowed during the study. results table 1. baseline characteristics of salt score ≤20 non-responders at week 24 ritlecitinib qd 200/50 mg (n=80) 200/30 mg (n=92) 50 mg (n=90) 30 mg (n=97) age mean (sd), years 34.9 (15.3) 34.3 (13.9) 31.9 (12.8) 32.8 (14.7) 12-17 years, n (%) 13 (16.3) 14 (15.2) 10 (11.1) 15 (15.5) ≥18 years, n (%) 67 (83.8) 78 (84.8) 80 (88.9) 82 (84.5) female, n (%) 44 (55.0) 57 (62.0) 43 (47.8) 55 (56.7) white, n (%) 56 (70.0) 65 (70.7) 54 (60.0) 63 (64.9) patients with at/au*, n (%) 45 (56.3) 49 (53.3) 49 (54.4) 48 (49.5) baseline salt score, mean (sd) all patients 93.3 (13.5) 92.9 (12.4) 93.6 (11.9) 92.1 (13.0) non-at/au 84.7 (17.0) 84.9 (14.4) 86.0 (14.4) 84.3 (14.7) duration of disease since aa diagnosis, mean (sd), years 9.2 (10.7) 11.6 (12.2) 9.2 (8.6) 8.5 (9.1) duration of current aa episode, mean (sd), years 3.7 (3.0) 3.5 (2.8) 3.5 (2.8) 3.6 (2.8) aa, alopecia areata; at, alopecia totalis; au, alopecia universalis; qd, once daily; salt, severity of alopecia tool; yrs, years. *patients in the at/au category had a salt score of 100 at baseline (regardless of the category in the aa history case report form). • of patients in the ritlecitinib groups who did not meet salt ≤20 response at week 24, 4.6–8.2% had a response at week 28, with rates increasing to 22.2–33.7% at week 48 (figure 2) figure 2. salt score ≤20 response over time after week 24 5.6 14.7 17.3 24.7 4.6 11.2 19.5 22.2 8.2 18.2 28.6 33.7 7.4 16.8 19.3 23.0 0 10 20 30 40 50 week 28 week 34 week 40 week 48 ritlecitinib 200/50 mg (n=80) ritlecitinib 200/30 mg (n=92) ritlecitinib 50 mg (n=90) ritlecitinib 30 mg (n=97) p at ie nt s w ith s a lt ≤ 20 r es po ns e, % (9 5% c i) 71 87 85 95 75 89 88 95 75 87 84 88 73 81 86 87n1: 4 4 7 7 11 10 16 16 13 17 24 17 18 18 29 20n: salt, severity of alopecia tool. n/n1 indicated for each timepoint; n: number of patients with response. n1: number of patients with salt score data at each timepoint. • of patients in the ritlecitinib groups who did not meet salt ≤10 response at week 24, 6.1–12.2% had a response at week 28, with rates increasing to 19.8–25.5% at week 48 (figure 3) figure 3. salt score ≤10 response over time after week 24 12.2 15.1 18.6 25.3 6.3 12.1 20.4 22.8 10.3 14.0 19.8 25.5 6.1 14.1 17.4 19.8 82 96 97 99 86 99 100 99 86 98 96 92 83 92 98 91 10 6 10 6 13 12 14 14 16 20 19 16 21 21 25 21 0 10 20 30 40 50 week 28 week 34 week 40 week 48 ritlecitinib 200/50 mg (n=91) ritlecitinib 200/30 mg (n=103) ritlecitinib 50 mg (n=102) ritlecitinib 30 mg (n=101) p at ie nt s w ith s a lt ≤ 10 r es po ns e, % (9 5% c i) n1: n: salt, severity of alopecia tool. n/n1 indicated for each timepoint; n: number of patients with response. n1: number of patients with salt score data at each timepoint. • of eba non-responders at week 24, 7.6–13.6% achieved response at week 28 and 19.7–32.8% at week 48 (figures 4) figure 4. eba responses over time after week 24* 10.3 18.3 23.3 24.6 8.5 13.7 12.7 19.7 7.6 14.9 21.5 32.8 13.6 21.0 25.0 27.0 58 71 66 81 60 73 67 81 60 71 65 76 57 66 67 75 6 6 5 11 11 10 10 17 14 9 14 19 14 13 22 20 0 10 20 30 40 50 week 28 week 34 week 40 week 48 ritlecitinib 200/50 mg (n=63) ritlecitinib 200/30 mg (n=76) ritlecitinib 50 mg (n=70) ritlecitinib 30 mg (n=83) p at ie nt s w ith e b a r es po ns e, % (9 5% c i) n1: n: eba, eyebrow assessment. n/n1 indicated for each timepoint; n: number of patients with response. n1: number of patients with eba data at each timepoint. *eba response defined as a normal score (3) or ≥2-grade improvement from baseline in the eba scale in patients without normal eba scores at baseline. • of ela non-responders at week 24, 4.4–15.0% achieved response at week 28 and 16.7–30.2% at week 48 (figure 5) figure 5. ela responses over time after week 24* 10.3 17.2 26.3 29.6 4.4 8.5 12.9 16.7 15.0 20.6 21.0 30.2 4.4 10.3 15.6 21.0 . 58 71 66 81 60 73 67 81 60 71 65 76 57 66 67 75 6 6 5 11 11 10 10 17 14 9 14 19 14 13 22 20 0 10 20 30 40 50 week 28 week 34 week 40 week 48 ritlecitinib 200/50 mg (n=62) ritlecitinib 200/30 mg (n=73) ritlecitinib 50 mg (n=65) ritlecitinib 30 mg (n=70) p at ie nt s w ith e la r es po ns e, % (9 5% c i) n1: n: ela, eyelash assessment. n/n1 indicated for each timepoint; n: number of patients with response. n1: number of patients with ela data at each timepoint. *ela response defined as a normal score (3) or ≥2-grade improvement from baseline in the ela scale in patients without normal ela scores at baseline. safety • ritlecitinib was well tolerated through week 48 in patients with aa • among patients who did not meet clinical response at week 24, the most common aes (≥5% of patients in any treatment group) were nasopharyngitis, nausea, headache, and folliculitis conclusions • target hair regrowth responses may be achieved at later time points with continued ritlecitinib treatment in patients with aa who do not initially achieve target response at week 24 study population • inclusion criteria: age ≥12 years aa with ≥50% scalp hair loss, including patients with alopecia totalis (at) and alopecia universalis (au) current aa episode duration of 6 months to 10 years • patients with other causes of alopecia or previous use of any jak inhibitor were excluded • this post hoc analysis included patients who received ritlecitinib 200/50, 200/30, 50, or 30 mg and did not have a clinical response at week 24 outcomes • this post hoc analysis assessed the proportions of ritlecitinib-treated patients who achieved clinical response between weeks 28 and 48, among those who did not meet clinical response criteria at week 24 separate criteria for non-response at week 24 were determined for each cohort: • salt score >20, or • salt score >10, or • no improvement in eyebrow assessment (eba) score (abnormal or <2-grade improvement from baseline) in patients with abnormal eba scores at baseline, or • no improvement in eyelash assessment (ela) score (abnormal or <2-grade improvement from baseline) in patients with abnormal ela scores at baseline clinical response at each timepoint was defined separately for each endpoint: • salt score ≤20, or • salt score ≤10, or • eba score (normal or ≥2-grade improvement from baseline) in patients with abnormal eba scores at baseline, or • ela score (normal or ≥2-grade improvement from baseline) in patients with abnormal ela scores at baseline statistical analysis • descriptive analyses were used to summarize the proportion of patients who achieved response at week 28, 34, 40, or 48, among those who did not meet clinical response criteria at week 24 • 95% cis were calculated based on normal approximation • post hoc analyses were based on observed data; patients with missing data at each timepoint were excluded from that timepoint � � � � � � � � � � � � � � 3 m 6 m 12 m 18 m follow-upfollow-up pdt-1 pdt-2 (if lesions remain) � � � � � � � 0 10 20 30 40 50 60 70 80 90 100 after 1. pdt after 1. and 2. pdt c om pl et el y c le ar ed p at ie nt s [% ] patient complete response [fas] bf-200 ala (n=55) placebo (n=32) 0 10 20 30 40 50 60 70 80 90 100 after 1. pdt after 1. and 2. pdt c om pl et el y c le ar ed l es io ns [% ] lesion complete response [fas] bf-200 ala (n=298) placebo (n=173) � � � skin surface hyperpigmentation hypopigmentation mottled pigmentation scarring atrophy 0.00 0.20 0.40 0.60 0.80 1.00 1.20 1.40 0.00 0.10 0.20 0.30 0.40 0.50 0.60 0.70 0.00 0.10 0.20 0.30 0.40 0.50 0.60 0.70 0.80 0.90 0.00 0.10 0.20 0.30 0.40 0.50 0.60 0.70 0.00 0.10 0.20 0.30 0.40 0.50 0.00 0.10 0.20 0.30 0.40 0.50 0 12 26 52 weeks after last pdt * * * * * * * * * * * * * * * * * 0 12 26 52 weeks after last pdt 0 12 26 52 weeks after last pdt 0 12 26 52 weeks after last pdt 0 12 26 52 weeks after last pdt 0 12 26 52 weeks after last pdt im p a ir m e n t s c o r e ( 0 3 ) im p a ir m e n t s c o r e ( 0 3 ) im p a ir m e n t s c o r e ( 0 3 ) im p a ir m e n t s c o r e ( 0 3 ) im p a ir m e n t s c o r e ( 0 3 ) im p a ir m e n t s c o r e ( 0 3 ) ± � � � � follow-up fc17posterbiofronteradirschkaphotodynamictherapyactinickeratosis.pdf skin march 2018 volume 2 issue 2 copyright 2018 the national society for cutaneous medicine 90 featured article l-carnitine reduces muscle cramps in patients taking vismodegib matthew s. dinehart ba m.ed a , stacy mcmurray md b , scott m. dinehart md c , mark lebwohl md d a university of arkansas for medical sciences, college of medicine, little rock, ar b department of dermatology, university of tennessee health science center, memphis, tn c arkansas dermatology, little rock, ar d department of dermatology, icahn school of medicine at mount sinai, new york, ny vismodegib is a novel oral smoothened (smo) antagonist, approved by the food and drug administration (fda) for the treatment of locally advanced (labcc) and metastatic (mbcc) basal cell carcinoma. 1 significant therapeutic results are obtained with vismodegib; however, adverse events often limit use to less than the time needed for optimal therapy. the most common side effect of hhis is muscle cramps, reported in about 60-70% of patients. 2,3 muscle cramps are a frequent source of patient dissatisfaction and often result in a significant negative impact on patient quality of life. we report 3 patients taking vismodegib who experienced a reduction in muscle cramps after starting l-carnitine, a dietary supplement. abstract vismodegib is an oral, small-molecule hedgehog pathway inhibitor (hhi) approved for the treatment of locally advanced and metastatic basal cell carcinoma. while an effective treatment option for these conditions, hhi therapy is associated with muscle cramps in a significant number of patients. this adverse effect negatively impacts patient quality of life and patient adherence to the prescribed treatment regimen. levocarnitine (l-carnitine) is a trimethylated amino acid known to play a critical role in lipid metabolism. it has antioxidant properties, and several studies have illustrated its effectiveness in lessening the severity of muscle cramps in various disease processes. we present three patients who developed muscle cramping associated with vismodegib treatment for basal cell carcinoma. each was started on l-carnitine therapy, and all three reported a significant decrease in the severity of their muscle cramps to the point that they were able to continue hhi therapy without taking a drug holiday. these cases illustrate a promising treatment option for the most common side effect associated with hhi treatment. introduction skin march 2018 volume 2 issue 2 copyright 2018 the national society for cutaneous medicine 91 the patient is a 74-year-old male who has been followed by his dermatologist for the treatment of an advanced basal cell carcinoma located in his right axilla, first diagnosed when he was 40 years old. shortly after initial presentation, the lesion was excised via mohs surgery, but clear margins were unable to be obtained, and the patient was treated with adjuvant radiation therapy. at the age of 46 the patient developed a mass in the right axilla, which, upon biopsy and subsequent excision, showed atypical basaloid cells. at the age of 52, pulmonary nodules were noted on chest x-ray. the nodules were biopsied and the pathological diagnosis of metastatic basal cell carcinoma was confirmed. the patient had previously been treated with oral acitretin 25 mg daily for the suppression of numerous prior basal cell and squamous cell carcinomas. at the age of 54 he was placed on 150 mg/day of vismodegib as part of a clinical trial. because of severe muscle cramps, the patient took numerous drug holidays, including periods off the drug for up to six months. these breaks from therapy resulted in pulmonary recurrences, which were then suppressed upon the resumption of vismodegib. on a 0 – 10 scale, the patient rated his muscle cramps as a 10, and cpk levels drawn during that time were as high as 1496 u/l (upper limit of normal 200 u/l). due to recurrence of his pulmonary metastases, the patient was restarted on vismodegib. he once again developed his typical 10/10 severe muscle cramping and requested to halt treatment. he was instead started l-carnitine 1000 mg twice daily and experienced a reduction in muscle cramps severity after several weeks on the supplement. he reported a decrease in cramp intensity from the earlier documented level of 10 to a level of 3. an 85-year-old caucasian woman presented with a bleeding, growing and painful mass on her nose. the lesion had been present for more than 2 years and had recurred from a previous mohs surgery performed 3 years ago at another institution. examination showed a 4x3 cm ill-defined mass involving her entire nasal tip with extension to part of her nasal bridge. biopsy revealed basal cell carcinoma, and the patient was given options of palliative radiation to the area or treatment with a hhi. the patient chose the latter and was started on vismodegib 150 mg once a day. at her one-month clinic visit, the patient was experiencing numerous side effects, the worst of which were muscle cramps. they occurred several times a day in her extremities and would frequently awaken her at night. she rated the cramps as a 5 on a visual analog scale of 0-10. she considered discontinuing the vismodegib due to the discomfort, but was hesitant because of the dramatic improvement in her nose lesion, which had stopped bleeding and shrunk considerably. she decided to continue her vismodegib therapy at 150 mg per day, with the addition of l-carnitine 1000 mg each night. at her two-month visit her tumor had continued to shrink. she also reported a notable decrease in muscle cramp severity. she now rated them a 1 out of 10 on the analog scale. she continued to report other side effects such as minimal hair loss and dysgeusia. over the next two months her tumor continued to improve and at the patient’s 4 month visit there was no tumor that could be identified visually. muscle cramps were not a significant problem, and she continued to rate them a 1 out of 10. at this visit the patient was offered the choice to take continue her current therapy or take vismodegib the first 10 days of each month for 6 months rather than have further case #1 case #2 skin march 2018 volume 2 issue 2 copyright 2018 the national society for cutaneous medicine 92 biopsies of her nose. she elected the latter treatment option and continued the l carnitine with her intermittent vismodegib dosing with no return of her muscle cramps. a 56-year-old woman was seen in consultation for biopsy proven basal cell carcinomas on her back, chest and left leg. she reported a previous surgery by a general surgeon to treat the tumor on her back. this tumor had recurred and had been steadily growing until it reached 22x20 cm in size. it had also recently begun to bleed. the tumors on her chest and left leg were smaller, both less than 2 cm in size. the patient was given options of surgery, radiation, or treatment with a hhi. she preferred a medical treatment course and was started on vismodegib 150 mg each day. after two months of treatment the smaller skin cancers were no longer clinically apparent and the larger tumor on her back, while still present, was significantly reduced in size. she also noted severe muscle cramps, occurring daily, that were beginning to hamper her employment. the patient rated these cramps as a 6 on a scale of 0 10. she was started on l-carnitine 1500 mg per day in hopes of reducing the muscle cramps. at her 4 month visit the patient noted a decrease in muscle cramps and rated their severity as a 2 on a scale of 0 10. her most significant complaint on this visit was a relative ageusia. she reported a 10-pound weight loss since beginning therapy. the tumor on her back had continued to shrink, with only 25 x 20 mm of basal cell carcinoma remaining. at this time, the patient was given the option of a reduced dosage schedule for the vismodegib or a drug holiday but she decided to continue the hhi with concurrent l-carnitine supplementation. imiquimod cream was added to her regimen in an attempt to hasten clearance of the lesion. she continues to be followed. vismodegib has a relatively benign safety profile, yet its use is often marked by multiple adverse events (aes) including muscle cramps, alopecia, dysgeusia, gastrointestinal complaints, and weight loss. between 95-100% of users experience at least one adverse event during the course of their hhi treatment. 4 muscle cramping is the most commonly reported ae with individual studies estimating that between 60-70% of users experience cramping. 2,3 these cramps often begin early during therapy, worsen with length of therapy and are a reason frequently cited by patients when requesting a drug holiday or discontinuation of treatment. while the mechanism is not fully understood, the spasms are believed to be related to the paradoxical activation of the noncanonical smo/ca 2+ /ampk axis and inhibition of the canonical smo signaling pathway by vismodegib, which results in ca 2+ influx into muscle cells and consequent muscle contraction. 5 a variety of options have been employed in an attempt to lessen or eliminate the cramps associated with hhi therapy. good hydration, gentle exercise, stretching, and massage have been suggested for mild cases of cramping. 4 in more severe cases different pharmacologic treatments have been used with variable effectiveness. ally et al found modest decreases in cramping within two weeks of starting treatment with calcium channel blockers. 6 case reports detailing medical marijuana and magnesium case #3 discussion skin march 2018 volume 2 issue 2 copyright 2018 the national society for cutaneous medicine 93 supplementation have been published. 7,8 other studies have suggested use of muscle relaxants such as low-dose cyclobenzaprine, baclofen, or quinine, though the latter is discouraged by the fda due to severe cardiac risks. 9,10 outside of pharmacologic approaches, some practitioners have found intermittent dosing of vismodegib to lessen cramps, and several trials are underway examining the clinical effectiveness of intermittent dosing. 11,12,13 levocarnitine (l-carnitine) is a non-essential amino acid that is found in almost all cells, but is concentrated in tissues like skeletal and cardiac muscle that utilize fatty acids as energy. it is naturally produced in the liver and kidneys and can be found in several dietary sources, mainly animal products such as red meat and dairy. 14 it has been found to be an effective treatment for muscle cramps that occur in end-stage renal disease patients on hemodialysis and those with liver cirrhosis. 15,16 l-carnitine can be obtained without a prescription because it is sold as a dietary supplement. l-carnitine produces energy in cells by transporting long chain fatty acids from the cytosol into mitochondria where they are oxidized to form adenosine triphosphate (atp). it is thought that this beta-oxidation of fatty acids in skeletal tissue produces energy that stabilizes the sarcolemma, thus allowing the muscle to rest. 17 optimal dosage for vismodegib-related cramps has yet to be determined, but 10002000 mg per day was sufficient to help our patients. adverse events from l-carnitine are uncommon, and its use appears to be reasonably safe. in one study, patients given 3000mg of l-carnitine each day for 21 days did not see any negative effects as assessed by a comprehensive blood panel which was conducted at the beginning and end of the study. 18 other studies have confirmed l-carnitine’s safety at dosages of 2000mg per day. 19 in these investigations mild adverse events, including nausea and stomach discomfort were noted. uncommon side effects included muscle weakness in uremic patients and seizures in those with known seizure disorders. 20 we are now routinely placing patients with advanced bcc on l-carnitine at the time they begin or before they begin vismodegib to prevent development of muscle cramps. future studies that help identify optimal dosage of l-carnitine for vismodegib associated muscle cramps would be beneficial. in addition, larger trials are needed to confirm the observations that we have documented in our 3 patients. conflict of interest disclosures: none. funding: none. corresponding author: matthew s. dinehart, ba, m.ed university of arkansas for medical sciences little rock, ar 501-650-2879 (office) 501-221-0214 (fax) msdinehart@gmail.com references: 1. sekulic a, migden mr, lewis k, et al. pivotal erivance basal cell carcinoma (bcc) study: 12-month update of efficacy and safety of vismodegib in advanced bcc. j am acad dermatol. 2015;72(6):1021-1026 e1028. 2. sekulic a, migden mr, oro ae, et al. efficacy and safety of vismodegib in advanced basal-cell carcinoma. n engl j med. 2012;366(23):2171-2179. skin march 2018 volume 2 issue 2 copyright 2018 the national society for cutaneous medicine 94 3. basset-seguin n, hauschild a, grob jj, et al. vismodegib in patients with advanced basal cell carcinoma (stevie): a pre-planned interim analysis of an international, open-label trial. lancet oncol. 2015;16(6):729736. 4. lacouture me, dreno b, ascierto pa, et al. characterization and management of hedgehog pathway inhibitorrelated adverse events in patients with advanced basal cell carcinoma. oncologist. 2016;21(10):1218-1229. 5. teperino r, amann s, bayer m, et al. hedgehog partial agonism drives warburg-like metabolism in muscle and brown fat. cell. 2012;151(2):414426. 6. ally ms, tang jy, lindgren j, et al. effect of calcium channel blockade on vismodegib-induced muscle cramps. jama dermatol. 2015;151(10):11321134. 7. yuan jt, tello tl, hultman c, barker ca, arron st, yom ss. medical marijuana for the treatment of vismodegib-related muscle spasm. jaad case rep. 2017;3(5):438-440. 8. garrison sr, allan gm, sekhon rk, musini vm, khan km. magnesium for skeletal muscle cramps. cochrane database syst rev. 2012(9):cd009402. 9. yang yw, macdonald jb, nelson sa, sekulic a. treatment of vismodegibassociated muscle cramps with cyclobenzaprine: a retrospective review. j am acad dermatol. 2017;77(6):1170-1172. 10. fife k, herd r, lalondrelle s, et al. managing adverse events associated with vismodegib in the treatment of basal cell carcinoma. future oncol. 2017;13(2):175-184. 11. yang x, dinehart sm. intermittent vismodegib therapy in basal cell nevus syndrome. jama dermatol. 2016;152(2):223-224. 12. dreno b, kunstfeld r, hauschild a, et al. two intermittent vismodegib dosing regimens in patients with multiple basal-cell carcinomas (mikie): a randomised, regimen-controlled, double-blind, phase 2 trial. lancet oncol. 2017;18(3):404-412. 13. mosterd k. intermittent vismodegib dosing to treat multiple basal-cell carcinomas. lancet oncol. 2017;18(3):284-286. 14. ca. s. carnitine deficiency disorders in children. ann ny acad sci 2004;1033:42-51. 15. goral s. levocarnitine and muscle metabolism in patients with end-stage renal disease. j ren nutr. 1998;8(3):118-121. 16. nakanishi h, kurosaki m, tsuchiya k, et al. l-carnitine reduces muscle cramps in patients with cirrhosis. clin gastroenterol hepatol. 2015;13(8):1540-1543. 17. longo n, frigeni m, pasquali m. carnitine transport and fatty acid oxidation. biochim biophys acta. 2016;1863(10):2422-2435. skin march 2018 volume 2 issue 2 copyright 2018 the national society for cutaneous medicine 95 18. rubin mr, volek js, gomez al, et al. safety measures of l-carnitine ltartrate supplementation in healthy men. j strength cond res. 2001;15(4):486-490. 19. cruciani ra, dvorkin e, homel p, et al. safety, tolerability and symptom outcomes associated with l-carnitine supplementation in patients with cancer, fatigue, and carnitine deficiency: a phase i/ii study. j pain symptom manage. 2006;32(6):551559. 20. hathcock jn, shao a. risk assessment for carnitine. regul toxicol pharmacol. 2006;46(1):23-28. skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 404 research letter why dermatology? a survey of factors influencing resident physician selection of a career in dermatology chinelo ikpeama, md, mba1, krystina gleghorn, md1, tara akunna, bba2, michael ryan, bs2, michael wilkerson, md1 1department of dermatology, the university of texas medical branch, galveston, tx 2school of medicine, the university of texas medical branch, galveston, tx choosing a medical specialty is an important decision, and each specialty has unique characteristics. dermatology, a field specialized in the treatment of skin, hair, and nails, has widespread appeal. this widespread appeal is supported by the competitive residency selection process and consistently high career satisfaction rates. in medscape’s 2017 physician compensation report, dermatologists reported a high career satisfaction rate. additionally, 80% of dermatologists would choose the same specialty again.1 currently, there are no studies in literature that address the reasons why residents choose dermatology as a career. this study will help determine what influenced dermatology residents and fellows to pursue a dermatology career. a 13-question web-based survey (www.surveymonkey.com/r/whyderm) was emailed to the residency program directors and coordinators of 121 accreditation council for graduate medical education (acgme)-approved dermatology residency programs. the residency program directors and/or coordinators then forwarded the survey to eligible residents and fellows. the email was sent in july 2017 and resent in october 2017. a total of 242 responses were received. the mean age of responses was 29.54 years old. of the responses, 41% were postgraduateyear two. residency geographic regions were diverse. eighty percent of responders had been to the dermatology clinic as a patient. of these responders, 66% were seen for acne (table i). table i: respondent characteristics. % of respondents (n = 242) age of respondents 29.54 years age of first exposure to dermatology 16.91 years dermatology year pgy2 40.9% pgy3 26.4% pgy4 28.9% fellow 3.7% area of country northwest 2.1% northeast 19.3% midwest 27.7% east 2.9% west 10.5% south 19.7% southeast 12.6% southwest 5.0% marital status single 39.0% married 57.1% engaged 2.5% partnered 0.01% skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 405 table i continued: resident and fellow survey responses. % of respondents (n = 242) do you have children? yes 18.4% no 81.5% do you have siblings? yes 93.6% no 6.3% are you the: only child 5.9% oldest child 40.4% middle child 20.8% youngest child 32.7% have you been to dermatology as a patient? yes 80.1% no 19.8% reason for first dermatology visit acne 66.9% dysplastic nevus 23.4% warts 13.0% atopic dermatitis 8.6% acne and dysplastic nevi 4.3% alopecia/hair 4.3% seborrheic dermatitis 4.3% skin exam 3.4% basal cell carcinoma 2.6% cyst 2.6% respondents were told to rank in descending order their top five factors in choosing a career in dermatology. in descending order, lifestyle, personal interest in dermatology, positive dermatology clerkship experience, dermatology mentor, and future job opportunities garnered the most responses (table ii). ninety-nine percent of respondents would choose dermatology as a specialty again (table i). the dermatology match is competitive, but the reasons why residents choose it as a specialty has not been evaluated in literature. interestingly, financial rewards and career prestige were not in the top five choices selected. table 2: respondents’ top 5 reasons for choosing dermatology. no. of respondents (n = 242) lifestyle 191 personal interest in dermatology 184 positive dermatology clerkship experience 159 influence from a mentor 131 future job opportunities in the field 118 financial rewards 116 career prestige 74 past personal history of a skin condition 67 family history of a skin condition 38 family exposure to the career 31 current personal history of a skin condition 27 geographical location 25 our survey was similar to other surveys that demonstrate that dermatology has a high career satisfaction rate1, as 99% of respondents would choose dermatology as a career again. in conclusion, our study demonstrates that surveyed residents and fellows are highly satisfied with their choice of dermatology as a medical career. lifestyle, personal interest in the field of dermatology, a positive dermatology clerkship experience, an exceptional mentor, and future dermatological job opportunities were the top five reasons why residents and fellows chose dermatology as a career in our survey. our data can help medical students who are contemplating dermatology as their future medical career. conflict of interest disclosures: none. funding: none. skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 406 corresponding author: chinelo ikpeama, md, mba 17903 west lake houston blvd humble, tx 77346 email: chinelo.ikpeama@gmail.com references: 1. grisham s. medscape physician compensation report 2017. medscape.com website. april 5, 2017. https://www.medscape.com/slideshow/c ompensation-2017-overview-6008547. accessed april 9, 2018. 2. pruthi s, pandey r, singh s, et. al. why does an undergraduate student choose medicine as a career? the national medical journal of india. 2013; 23(3): 147. 3. west cp, dupras dm. general medicine vs. subspecialty career plans among internal medicine residents. jama. 2012 dec 5;308(21)2241-7. mostaghimi a, wanat k, crotty bh, rosenbach m. a national survey of residents in combined internal medicine and dermatology residency programs: educational experience and future plans. dermatol online j. 2015 oct 16;21(10). mailto:chinelo.ikpeama@gmail.com presented at the 2020 fall clinical dermatology conference, october 29 november 1, 2020. treatment success in mild psoriasis patients with fixed-combination calcipotriene and betamethasone dipropionate (cal/bd) foam: results from the pso-fast trial karen a. veverka, phd,1 jes b. hansen, phd,1 maria yaloumis, pharmd,1 leon kircik, md,2 and linda stein gold, md3 1leo pharma, madison, nj; 2icahn school of medicine at mount sinai, new york, ny; indiana university school of medicine, indianapolis, in; physicians skin care, pllc, louisville, ky; 3henry ford hospital, detroit, mi introduction • psoriasis is a chronic skin disease affecting approximately 2% of the worldwide population characterized by sharply demarcated, scaling, and erythematous plaques that may be painful and often severely pruritic1 • while topical therapy is the regimen of choice for patients with less extensive disease,2 very few of these therapies have been demonstrated effective for mild psoriasis – treatment success in this population requires that visible disease be completely cleared (i.e., improvement of investigator’s global assessment (iga) score from 2 to 0) • corticosteroids and vitamin d analogues are among the most common treatments that are either used alone or in combination2,3 • topical, fixed-combination calcipotriene (50 µg/g) plus betamethasone dipropionate (0.5 mg/g; cal/bd) cutaneous foam is indicated for the treatment of plaque psoriasis in patients 12 years and older4 – in a phase iii, double-blind, randomized study that included patients with all severities of psoriasis (pso-fast), cal/bd foam was efficacious and well tolerated, and also provided rapid treatment responses with significant itch relief3 objective • to compare the efficacy of treatment with cal/bd foam to that of treatment with vehicle for up to 4 weeks in patients with mild psoriasis vulgaris by performing a post hoc analysis of the pso-fast trial materials and methods study design • pso-fast was a phase iii, randomized, multicenter (us), double-blind, vehicle-controlled, 4-week study (nct01866163) • 426 patients were randomized (3:1) to cal/bd foam or foam vehicle once daily for up to 4 weeks figure 1. study design key inclusion criteria key exclusion criteria treatments within specified time periods prior to randomization: • systemic biological therapies (4-16 weeks/5 half-lives) • all other systemic treatments (4 weeks) • non-marketed drugs (4 weeks/5 half-lives) • puva therapy (4 weeks) • uvb therapy (2 weeks) • topical anti-psoriatic treatment (2 weeks) • ≥18 years of age • males and non-pregnant females • psoriasis diagnosis ≥6 months • igaa of at least mild on trunk and/or limbs • 2-30% bsa on trunk and/or limbs • mpasi score ≥2 randomized 3:1 cal/bd foam self-applied 1/day (n=323) vehicle foam self-applied 1/day (n=103) day 0 week 1 week 2 week 4 endpoint assessments • percent of patients achieving treatment success at week 4b • mpasi-75 at week 4 • percent reduction in mpasi from baseline to weeks 1, 2, and 4 ainvestigator’s global assessment (iga) of disease severity was scored on a 5-point scale: 0=clear, 1=almost clear, 2=mild, 3=moderate, 4=severe. btreatment success for patients with mild disease severity at baseline was defined as clear (iga=0). results patient population • at baseline, 65/426 patients had mild plaque psoriasis • baseline demographics and disease characteristics are shown in table 1 • overall, treatment groups were well balanced for patient characteristics and baseline demographics within this subpopulation • both mean bsa and mean mpasi at baseline were comparable between groups table 1. baseline demographics and disease characteristics for randomized patients with mild psoriasis (iga=2) baseline characteristic cal/bd foam (n=50) vehicle foam (n=15) overall (n=65) mean age, years 48.6 42.2 47.2 median age, years (range) 52.5 (19-79) 38.0 (20-74) 50.0 (19-79) male, % 56.0 46.7 53.8 fitzpatrick skin type, % type i 2.0 0.0 1.5 type ii 42.0 20.0 36.9 type iii 26.0 40.0 29.2 type iv 18.0 20.0 18.5 type v 6.0 20.0 9.2 type vi 6.0 0.0 4.6 mean bmi, kg/m2 31.5 31.5 31.5 mean pso duration, years 16.0 9.1 14.4 mean bsa, % (sd) 4.5 (2.6) 5.7 (4.2) 4.8 (3.1) mean mpasi (range) 4.7 (2-16) 5.0 (2-8) 4.7 (2-16) efficacy: iga treatment success • at week 4, significantly more patients with mild psoriasis achieved treatment success with cal/bd foam than foam vehicle (30.6% vs 0.0%, p<.001) (figure 2) – treatment success was observed as early as week 2 with cal/bd foam vs vehicle (8.2% vs 0%) (data not shown) figure 2. iga treatment success at week 4 for patients with mild, moderate, or severe psoriasis at baseline 30.6% 60.0% 37.9% 0.0% 4.2% 7.7% 0 25 50 75 100 mild moderate severe tr ea tm en t su cc es s (% o f p ati en ts ) cal/bd foam vehicle foam p<.001 p=.019 p=.048 mantel-haenszel odds of treatment success in cal/bd group relative to vehicle group. efficacy: severity outcomes • mild patients achieved significantly greater reductions in bsa (figure 3a) and mpasi scores (figure 3b) relative to baseline with cal/bd foam vs vehicle foam – the significant improvements were seen as early as week 1 and persisted to week 4 • mpasi-75 was significantly greater with cal/bd foam vs vehicle foam (49% vs 7.1%, p=.023) at week 4 (figure 4). figure 3. psoriasis severity outcomes for patients with mild pso at baseline -35.5% -55.3% -71.9% -15.2% -25.0% -27.7% -100 -75 -50 -25 0 week 1 week 2 week 4 re du cti on in m pa si fr om b as el in e (% ) -1.2 -1.8 -2.7 0.1 -0.5 -0.6 -5 -4 -3 -2 -1 0 1 week 1 week 2 week 4 a bs ol ut e bs a r ed uc ti on fr om b as el in e a b cal/bd foam vehicle foam p=.007 p=.057 p<.001 p=.053 p=.003 p<.001 a, absolute reduction in bsa from baseline to weeks 1, 2, and 4. b, percent reduction in mpasi from baseline to weeks 1, 2, and 4. figure 4.  mpasi-75 for patients with mild disease severity at baseline p=.24 p=.083 p=.023 12.2% 30.6% 49.0% 0.0% 7.7% 7.1% 0 25 50 75 100 week 1 week 2 week 3 cal/bd foam vehicle foam m pa si -7 5 (% ) mantel-haenszel odds of treatment success in cal/bd group relative to vehicle group, adjusted for pooled center. conclusions • in this post hoc analysis, once-daily fixed-dose combination cal/bd foam was efficacious in treating mild plaque psoriasis – importantly, while numerous other topical and systemic therapies are available for psoriasis, very few have demonstrated efficacy in this subpopulation • these important results establish treatment success for cal/bd foam in mild psoriasis, a population in which efficacy is difficult to demonstrate since the treatment must completely clear visible disease to be considered effective • the once-daily, cal/bd foam may provide a valuable treatment option for patients with mild plaque psoriasis references 1. menter a, gottlieb a, feldman sr, et al. guidelines of care for the management of psoriasis and psoriatic arthritis. j am acad dermatol. 2009;58(5):826-850. 2. menter a, korman nj, elmets ca, et al. guidelines of care for the management and treatment of psoriasis and psoriatic arthritis. j am acad dermatol. 2009;60:643-659. 3. leonardi c, bagel j, yamauchi p, et al. efficacy and safety of calcipotriene plus betamethasone dipropionate aerosol foam in patients with psoriasis vulgaris – a randomized phase iii study (pso-fast). j drugs dermatol. 2015;14(2):1468-1477. 4. enstilar (calcipotriene and betamethasone dipropionate) foam prescribing information, madison, nj: leo pharma, inc. disclosures drs. ka veverka, jb hansen and m yaloumis are employees of leo pharma inc. dr. kircik has served as a research investigator, speaker, and consultant for leo pharma, inc. dr. l stein gold serves as a consultant, speaker, advisory board participant, or investigator for leo pharma inc., taro pharmaceutical industries ltd., and mayne pharma. funding this study was funded by leo pharma inc. abbreviations bmi, body mass index; bsa, body surface area; cal/bd, calcipotriene/betamethasone dipropionate; iga, investigator’s global assessment; mpasi, modified (excluding head) psoriasis area and severity index; mpasi-75, 75% reduction in the mpasi; pso, psoriasis; puva, psoralen combined with ultraviolet a; sd, standard deviation; uvb, ultraviolet b. acknowledgments editorial support was provided by p-value communications. powerpoint presentation 0 –5 –10 –15 0 10 20 30 40 p e rc e n ta g e o f p a ti e n ts w it h a n i g a re s p o n s e 0 10 20 30 40 p e rc e n ta g e o f p a ti e n ts w it h a n i g a re s p o n s e a phase 2b dose-ranging efficacy and safety study of tralokinumab in adult patients with moderate to severe atopic dermatitis (ad) andreas wollenberg,1 michael d. howell,2 emma guttman-yassky,3 jonathan i. silverberg,4 claire birrell,5 christopher kell,6 koustubh ranade,2 michelle dawson,6 rené van der merwe6 1ludwig maximillian university, munich, germany; 2medimmune, llc, gaithersburg, md, usa; 3mount sinai school of medicine, new york, ny, usa; 4northwestern university feinberg school of medicine, chicago, il, usa; 5vhsquared ltd, cambridge, uk; 6medimmune, ltd, cambridge, uk poster presented at the american academy of dermatology meeting in orlando, fl; march 3-7, 2017. ▪ novel, well-tolerated treatments that target the molecular pathways underlying atopic dermatitis (ad), rather than symptomatic relief, are needed ▪ interleukin (il)-13, a type 2 t helper cytokine, has been implicated in the pathophysiology of ad1–4 and is reportedly upregulated in acute and chronic lesions5 ▪ tralokinumab is an immunoglobulin g4 human monoclonal antibody that potently and specifically neutralizes il-13.6 we report the findings from a phase 2b study of tralokinumab in patients with moderate to severe ad ▪ serum dipeptidyl peptidase 4 (dpp-4) has been reported as a predictive biomarker for tralokinumab efficacy in patients with severe asthma7 introduction figure 1. study design tralokinumab 45 mg sc q2w + tcs (n=51) tralokinumab 150 mg sc q2w + tcs (n=50) tralokinumab 300 mg sc q2w + tcs (n=51) placebo sc q2w + tcs (n=52) adults aged 18–75 years, with a diagnosis of moderate to severe ad >1 year prior to screening ▪ ad involvement of ≥10% of body surface area ▪ easi of ≥12 ▪ scorad of ≥25 ▪ iga score of ≥3 maintenance tcs –2 weeks 0 run-in period treatment period –6 screening period 2212 follow-up period primary endpoint r a n d o m iz e i n 1 :1 :1 :1 r a ti o study design • this was a phase 2b, randomized, double-blind, placebo-controlled, dose-ranging study (nct02347176) with a 12-week treatment period (figure 1) • patients were randomized to receive tralokinumab (45, 150, or 300 mg) following a 2‐week run-in period with class 3 (mid-strength) topical corticosteroids (tcs, administered throughout the study) (figure 1) assessments co-primary efficacy analyses (itt [intention-to-treat] population) • change from baseline in total eczema area and severity index (easi) at week 12 • percentage of investigator’s global assessment (iga) responders (patients achieving an iga score of 0 or 1, and at least a 2-grade reduction from baseline at week 12) secondary analyses (itt population) • change from baseline in scoring of atopic dermatitis (scorad) • change from baseline in pruritus numerical rating scale (nrs) (7-day mean score) • change from baseline in dermatology life quality index (dlqi) • percentage of patients achieving ≥50% reduction from baseline in easi (easi 50) • percentage of patients achieving ≥50% reduction from baseline in scorad (scorad 50) • staphylococcus aureus (s. aureus) colonization and infection were measured on lesional and nonlesional skin exploratory analysis (dpp-4 subpopulations) • primary endpoints were assessed in a subpopulation of patients with concentrations of dpp‐4 equal to or above (dpp-4-high) or below (dpp-4-low) the total population median at baseline safety (as-treated population) • most frequent treatment-emergent adverse events (teaes) and treatment‐emergent serious adverse events (tesaes) statistical analysis • continuous endpoints (change from baseline in easi, scorad, pruritus nrs, and dlqi) were analyzed using repeated measures analysis, adjusting for baseline • binary endpoints (iga, easi 50, and scorad 50 responders, and s. aureus status) were analyzed using logistic regression, adjusting for each baseline endpoint value • other endpoints were summarized descriptively methods results • 204 patients were randomized to treatment and 172 (84.3%) completed the study (figure 2) • demographics and baseline disease characteristics were similar between treatment groups (table 1) ae, adverse event figure 2. patient disposition discontinuation, n (%) lost to follow-up, 2 (3.9) withdrawal of consent, 8 (15.7) ae, 1 (2.0) other, 3 (5.9) total, 14 (27.5) placebo (n=51) randomized (n=204) patients/ screened (n=299) screening failures (n=95) did not meet inclusion/exclusion criteria (n=76) lost to follow-up (n=4) withdrawal of consent (n=9) other (n=6) discontinuation, n (%) lost to follow-up, 1 (2.0) withdrawal of consent, 3 (6.0) ae, 1 (2.0) other, 2 (4.0) total, 7 (14.0) tralokinumab 45 mg (n=50) discontinuation, n (%) lost to follow-up, 0 withdrawal of consent, 3 (5.9) ae, 2 (3.9) other, 2 (3.9) total, 7 (13.7) tralokinumab 150 mg (n=51) discontinuation, n (%) lost to follow-up, 1 (1.9) withdrawal of consent, 3 (5.8) ae, 0 other, 0 total, 4 (7.7) tralokinumab 300 mg (n=52) tralokinumab + tcs placebo q2w (n=51) 45 mg q2w (n=50) 150 mg q2w (n=51) 300 mg q2w (n=52) age, years, mean (sd) 39.4 (14.5) 39.1 (15.1) 37.1 (14.0) 35.7 (14.6) male, n (%) 22 (43.1) 29 (58.0) 26 (51.0) 33 (63.5) racea, n (%) asian 10 (19.6) 11 (22.0) 8 (15.7) 16 (30.8) black or african-american 8 (15.7) 4 (8.0) 10 (19.6) 7 (13.5) white 31 (60.8) 33 (66.0) 33 (64.7) 28 (53.8) other 1 (2.0) 1 (2.0) 0 0 total easi, mean (sd) 26.4 (12.6) 24.8 (8.3) 27.1 (11.2) 27.3 (10.9) baseline igab, n (%) moderate 31 (60.8) 32 (64.0) 31 (60.8) 29 (55.8) severe 20 (39.2) 18 (36.0) 16 (31.4) 20 (38.5) very severe 0 0 4 (7.8) 3 (5.8) total scorad, mean (sd) 58.5 (12.9) 57.5 (12.6) 60.8 (11.9) 60.8 (12.3) table 1. demographics and baseline disease characteristics (itt population) aeach race category contains patients who only selected this category bper the inclusion/exclusion criteria, no patient had a baseline iga of clear, almost clear or mild easi, eczema area and severity index; iga, investigator’s global assessment; itt, intention-to-treat; q2w, every 2 weeks; scorad, scoring of atopic dermatitis; sd, standard deviation; tcs, topical corticosteroids efficacy primary analyses • at week 12, tralokinumab 150 mg and 300 mg significantly reduced total easi from baseline (adjusted mean difference [standard error; se]: –4.4 [2.0] p=0.027 and –4.9 [1.9] p=0.011, respectively), compared with placebo (figure 3a) • a greater number of patients treated with tralokinumab 150 mg and 300 mg had an iga response of 0 or 1 at week 12, compared with placebo (figure 3b) figure 3. adjusted mean change from baseline in easi (a) and the percentage of patients with an iga response at week 12 (b) (itt population) secondary analyses • a significant decrease in scorad from baseline to week 12 was demonstrated for tralokinumab 150 mg (p=0.003) and 300 mg (p=0.002), compared with placebo (figure 4a) • patients treated with tralokinumab had lower pruritus scores at week 12, compared with placebo (figure 4b) • treatment with tralokinumab 300 mg was associated with a significant decrease in dlqi score at week 12 (p=0.006), compared with placebo (figure 4c) • at week 12, tralokinumab 300 mg significantly reduced s. aureus colonization on lesional and nonlesional skin, compared with placebo (p<0.001) figure 4. adjusted mean change from baseline in scorad (a), pruritus nrs (b), and dlqi (c) (itt population) dlqi, dermatology life quality index; itt, intention-to-treat; nrs, numerical rating scale; scorad, scoring of atopic dermatitis; se, standard error; tcs, topical corticosteroids placebo + tcs tralokinumab 45 mg + tcs tralokinumab 150 mg + tcs tralokinumab 300 mg + tcs –30 post-treatment period 0 –5 –10 0 2 4 6 8 10 12 16 22 weeks a d ju s te d m e a n c h a n g e in s c o r a d ( ± s e ) –25 –15 –20 a) * * * * * * * * * * * * * * * * b) post-treatment period a d ju s te d m e a n c h a n g e in p ru ri tu s n r s ( ± s e ) 0 –0.5 0 2 4 6 8 12 14 16 weeks –2.5 –1.0 –1.5 –2.0 101 3 5 7 11 13 159 * * ** * * * ** * * * * * post-treatment period a d ju s te d m e a n c h a n g e i n d l q i (± s e )c) 6 12 0 –2 –4 –8 0 22 weeks –6 * * *p≤0.05, compared with placebo a) b) easi, eczema area and severity index; iga, investigator’s global assessment; itt, intention-to-treat; se, standard error; tcs, topical corticosteroids n=50 n=50 n=51 n=51p e rc e n ta g e o f p a ti e n ts w it h a n i g a r e s p o n s e a d ju s te d m e a n c h a n g e in e a s i (± s e ) 0 2 4 6 8 10 12 16 22 weeks post-treatment period * * ** placebo + tcs tralokinumab 150 mg + tcs tralokinumab 45 mg + tcs tralokinumab 300 mg + tcs * * * * * * * * * 0 10 20 30 11.8 19.4 11.6 26.4 n=50 n=50 n=51 n=51 *p≤0.05, compared with placebo • 37 (73.1%) patients treated with tralokinumab 300 mg reached easi 50, demonstrating a significant increase of 21.4% (p=0.025) in response rates, compared with placebo (figure 5a) • significantly more patients treated with tralokinumab 150 mg (p=0.007) and tralokinumab 300 mg (p=0.007) achieved scorad 50 at week 12, compared with placebo (figure 5b) figure 5. percentage of patients achieving easi 50 (a) and scorad 50 (b) at week 12 (itt population) a) b) n=50 n=50 n=51 n=51 n=50 n=50 0 20 40 60 80 easi 50 (week 12) p e rc e n ta g e o f p a ti e n ts n=50 n=50 n=51 n=51 51.7 54.1 67.0 73.1 exploratory analysis • at week 12, all doses of tralokinumab demonstrated a significant reduction in easi from baseline compared with placebo (p<0.05) for patients in the dpp-4-high subpopulation • tralokinumab 300 mg demonstrated a significant increase in iga response at week 12 compared with placebo (p=0.025) for patients in the dpp-4-high subpopulation. numerical improvements were observed for all treatment groups, compared with placebo • significant differences in either primary endpoint were not observed for the dpp‐4‐low subpopulation at week 12 (figure 6) figure 6. adjusted mean change from baseline in easi (dpp-4-low [a] and ‐high [b] subpopulations) and the percentage of patients with an iga response at week 12 (dpp-4-low [c] and -high [d] subpopulations) dpp-4, dipeptidyl peptidase 4; easi, eczema area and severity index; iga, investigator’s global assessment; se, standard error; tcs, topical corticosteroids c) d) 22 b) weeks –25 post-treatment period0 –5 –10 0 2 4 6 8 10 12 16 –15 –20 a) a d ju s te d m e a n c h a n g e fr o m b a s e li n e i n e a s i (± s e ) * post-treatment period a d ju s te d m e a n c h a n g e fr o m b a s e li n e i n e a s i (± s e ) 0 –5 –25 –10 –15 –20 0 2 4 6 8 10 12 16 22 weeks * * * * * * * * * * * * * * * * * * * * n=24 n=25 n=23 n=29n=26 n=25 n=28 n=21 *p≤0.05, compared with placebo 15.4 12.0 25.0 14.3 8.3 12.0 13.0 34.5 0 10 20 30 40 50 scorad 50 (week 12) p e rc e n ta g e o f p a ti e n ts n=50 n=50 n=51 n=51 19.1 26.3 44.0 44.0 easi, eczema area and severity index; itt, intention-to-treat; scorad, scoring of atopic dermatitis; tcs, topical corticosteroids safety • teaes and tesaes are shown in table 2 tralokinumab + tcs placebo q2w (n=51) 45 mg q2w (n=50) 150 mg q2w (n=51) 300 mg q2w (n=52) total (n=204) at least one teae, n (%) 31 (60.8) 36 (72.0) 35 (68.6) 30 (57.7) 132 (64.7) at least one teae leading to discontinuationa, n (%) 5 (9.8) 2 (4.0) 3 (5.9) 0 10 (4.9) most common teaes, occurring in ≥5% of patients, n (%) nasopharyngitis 5 (9.8) 11 (22.0) 6 (11.8) 12 (23.1) 34 (16.7) upper respiratory tract infection 5 (9.8) 5 (10.0) 5 (9.8) 4 (7.7) 19 (9.3) headache 2 (3.9) 3 (6.0) 4 (7.8) 4 (7.7) 13 (6.4) ad 4 (7.8) 3 (6.0) 3 (5.9) 3 (5.8) 13 (6.4) at least one tesae, n (%) 1 (2.0) 3 (6.0) 2 (3.9) 0 6 (2.9) aone patient treated with tralokinumab 45 mg withdrew consent for further participation in the study and began treatment with cyclosporine a and clobegalen cream for ad. the patient later died from a cardiac event that was not considered related to treatment with tralokinumab ad, atopic dermatitis; q2w, every 2 weeks; tcs, topical corticosteroids; teae, treatment-emergent adverse event; tesae, treatment-emergent serious adverse event table 2. teaes and tesaes (as-treated population) • in this phase 2b study of patients with moderate to severe ad symptoms (despite daily treatment with class 3 tcs), tralokinumab demonstrated efficacy in the primary and key secondary endpoints, and an acceptable safety and tolerability profile, compared with placebo • furthermore, tralokinumab demonstrated significant improvements in quality of life (as shown by reduction in dlqi) and pruritus, compared with placebo • patients treated with tralokinumab 300 mg in the dpp-4-high subgroup demonstrated significant efficacy in both primary endpoints compared with placebo; the observed effect sizes were greater than in the itt population, suggesting that dpp-4 may serve as a predictive biomarker for patients who may benefit from tralokinumab treatment • however, treatment with class 3 tcs may have impacted on efficacy effect sizes observed, providing a limitation to the study design • these data suggest that targeting il-13 is a promising approach for ad treatment. clinical efficacy and dose response across a range of relevant endpoints supports the further evaluation of tralokinumab in this disease • 6/204 (2.9%) patients had a teae of conjunctivitis during the study (2 [3.9%],1 [2.0%], and 3 [5.9%] were treated with placebo, and tralokinumab 45 and 150 mg, respectively) • injection-site reactions of incidence ≥1% were bruising (1.0%), pain (1.5%), and reaction (1.0%). of these, all patients were treated with tralokinumab except for 1 patient in the placebo group who experienced some injection-site pain conclusions references 1. kim be, et al. clin immunol 2008;126:332–337. 2. howell md, et al. j invest dermatol 2008;128:2248–2258. 3. eyerich k, et al. j allergy clin immunol 2009;123:59–66. 4. khattri s, et al. j allergy clin immunol 2014;133:1626–1634. 5. gittler jk, et al. j allergy clin immunol 2012;130:1344–1354. 6. may rd, et al. br j pharmacol 2012;166:177–193. 7. panettieri ra, et al. clin invest 2015;5:701–711. acknowledgments this study was funded by medimmune. medical writing support was provided by rebecca plant, msc, qxv communications (an ashfield business, part of udg healthcare plc), macclesfield, uk, and was funded by medimmune. disclosures a. wollenberg is a consultant for almirall, celgene, leo pharma, l’oreal, medimmune, novartis pharma, pierre fabre, and regeneron. m.d. howell, c. kell, k. ranade, m. dawson, and r. van der merwe are shareholders of medimmune. e. guttman-yassky received research support from celgene, eli lilly, glenmark generics inc., janssen pharmaceuticals inc., leo pharmaceuticals, medimmune, novartis, regeneron, and vitae, and is a consultant for abbvie, anacor pharmaceuticals inc., celgene, dermira, galderma research & development llc, glenmark generics inc., leo pharmaceuticals, medimmune, novartis, pfizer, regeneron, sanofi-aventis, steifel/glaxosmithkline, vitae, mitsubishi pharma, eli lilly, asana biosciences, kyowa hakko kirin pharma inc., and almirall. j.i. silverberg is a consultant for anacor, abbvie, glaxosmithkline, eli lilly, medimmune, pfizer, and regeneron sanofi. c. birrell is a shareholder of astrazeneca. placebo + tcs tralokinumab 150 mg + tcs tralokinumab 45 mg + tcs tralokinumab 300 mg + tcs placebo + tcs tralokinumab 150 mg + tcs tralokinumab 45 mg + tcs tralokinumab 300 mg + tcs easi, eczema area and severity index; iga, investigator’s global assessment; q2w, every 2 weeks; sc, subcutaneous; scored, scoring of atopic dermatitis; tcs, topical corticosteroids medimmune’s product mentioned is investigational and not approved in any country. acknowledgements: medical writing support was provided by prescott medical communications group (chicago, il) with financial support from ortho dermatologics; ortho dermatologics is a division of bausch health us, llc • presented at the pa & np fall clinical dermatology conference • june 9-11, 2023 • orlando, fl monthly usage of efinaconazole 10% solution in two phase 3 randomized trials: is one 4-ml bottle enough for proper treatment? steven r feldman, md, phd1; shari r lipner, md, phd2; tracey c vlahovic, dpm3; warren s joseph, dpm4; c ralph daniel, md5; boni elewski, md6, phebe rich, md7 1wake forest school of medicine, winston-salem, nc; 2weill cornell medicine, new york, ny; 3temple university school of podiatric medicine, philadelphia, pa; 4arizona college of podiatric medicine, midwestern university, glendale, az; 5university of mississippi medical center, jackson, ms; 6university of alabama at birmingham school of medicine, birmingham, al; 7oregon health and science university, portland, or synopsis � topical therapies for onychomycosis require extended treatment durations, and incomplete or intermittent treatment can contribute to high rates of reinfection or relapse1 � excellent adherence to treatment is necessary to maximize efficacy,2 and prescribing an adequate quantity of medication is essential for good adherence � efinaconazole 10% topical solution—an azole antifungal used to treat onychomycosis in patients aged 6 years and older—is available in 4or 8-ml bottles � in the absence of data on patient characteristics influencing the amount of efinaconazole needed, 87% of efinaconazole prescriptions in 2022 were written for one 4-ml bottle per month3 objectives � to determine monthly efinaconazole usage by baseline patient demographics and clinical characteristics methods � two identical, double-blind, phase 3 studies (nct01008033; nct01007708) enrolled adult participants (18–70 years; n=1655) with mild-to-moderate distal lateral subungual onychomycosis affecting 20–50% of ≥1 great (target) toenail4 � participants were randomized (3:1) to treatment with efinaconazole 10% solution or vehicle, self-applied once daily for 48 weeks � bottles of study product (10 ml) were weighed upon dispensation at each study visit (every 4 weeks) and upon return at the following visit � monthly efinaconazole use was analyzed post hoc based on the total number of affected toenails and percent involvement of the target toenail at baseline as well as body mass index (bmi) and sex results � at baseline, efinaconazole-treated participants in both studies (n=656 and 580) had on average over one-third involvement of their target toenails (36.2% and 36.7%) and 3.7–3.8 affected toenails4 � among efinaconazole-treated participants with usage data for this analysis (n=1067), 85% had target toenail involvement of ≥25%, and over 55% had ≥4 affected toenails � as expected, percent involvement of the target toenail, bmi, or sex did not significantly impact average monthly efinaconazole usage (figure 1) � among participants with ≥2 affected toenails (90%), average monthly efinaconazole usage was equivalent to 1.10–1.59 4-ml bottles per month (figure 2) • only participants with one affected toenail used <4 ml of efinaconazole monthly • for patients with 6 affected toenails, one 4-ml bottle of efinaconazole would provide an average of 19 days of treatment figure 1. monthly efinaconazole use by baseline severity at target (great) toenail, bmi, and sex 0 p ro d u ct u se d ( m l) 14 16 12 10 8 6 4 2 ≥30 349 25 to <30 423 <25 293 bmi (kg/m2) male 823 female 244 sex ≥25% 908159 <25% n= target nail involvement average number of 4-ml bottles needed (monthly): 4.69 5.23 4.81 5.29 5.26 4.71 5.28 monthly medication use was calculated by converting mean daily use (in grams) to monthly use (in ml) using a 30-day month and the density of efinaconazole 10% solution. data are presented as mean ± standard deviation. diamonds indicate maximum monthly usage for each group. dashed line indicates usage above which more than one 4-ml bottle would be needed per month. bmi, body mass index. figure 2. monthly efinaconazole use by number of affec ted toenails 0 p ro d u ct u se d ( m l) 14 16 12 10 8 6 4 2 n= number of toenails treated average number of 4-ml bottles needed (monthly): 107 1 3.10 196 2 4.39 164 3 4.74 206 4 5.52 204 5 5.78 190 6 6.36 monthly medication use was calculated by converting mean daily use (in grams) to monthly use (in ml) using a 30-day month and the density of efinaconazole 10% solution. data are presented as mean ± standard deviation. diamonds indicate maximum monthly usage for each group. dashed line indicates usage above which more than one 4-ml bottle would be needed per month. conclusions � in this large sample of patients with onychomycosis, most had 2 or more affected toenails and used on average more than 4 ml of efinaconazole per month � in contrast, almost 90% of patients in clinical practice are prescribed only one 4-ml bottle monthly, demonstrating a potential disconnect between product need and amount provided to patients � most patients with onychomycosis of ≥2 toenails may find that one 4-ml bottle of medication runs out in less than a month, leaving gaps in treatment until prescriptions can be refilled • this may prolong time to achieve clinical effects and increase the likelihood of relapse or reinfection1 � given that nail percent involvement, sex, and bmi do not affect medication usage, number of affected nails should be the major consideration when determining monthly efinaconazole quantity to prescribe • clinicians should consider prescribing the larger 8-ml bottle of efinaconazole to patients with onychomycosis of more than one affected toenail references 1. lasenna ce and tosti a. patient pref adherence. 2015;9:887–891. 2. lipner sr and ko d. cutis. 2018;102(6):389–390. 3. ortho dermatologics. data on file. 2022. 4. elewski be, et al. j am acad dermatol. 2013;68(4):600–608. author disclosures steven r feldman has received research, speaking and/or consulting support from bms, eli lilly and company, glaxosmithkline/stiefel, abbvie, janssen, alovtech, vtv therapeutics, bristol-myers squibb, samsung, pfizer, boehringer ingelheim, amgen, dermavant, arcutis, novartis, novan, ucb, helsinn, sun pharma, almirall, galderma, leo pharma, mylan, celgene, ortho dermatologics, menlo, merck & co, qurient, forte, arena, biocon, accordant, argenx, sanofi, regeneron, the national biological corporation, caremark, teladoc, eurofins, informa, uptodate and the national psoriasis foundation. he is founder and part owner of causa research and holds stock in sensal health. shari r. lipner has served a consultant for ortho dermatologics, hoth therapeutics, moberg pharmaceuticals, and belletorus corporation. tracey c vlahovic has served as investigator and speaker for ortho dermatologics. warren s joseph has served as consultant and speaker for ortho dermatologics. c ralph daniel has provided clinical research support to ortho dermatologics and owns stock in medimetriks pharmaceuticals. boni elewski has provided clinical research support (research funding to university) for abbvie, anaptys-bio, boehringer ingelheim, bristol-myers squibb, celgene, incyte, leo pharma, lilly, merck, menlo, novartis, pfizer, regeneron, sun pharma, ortho dermatologics, and vanda; and as consultant (received honorarium) from boehringer ingelheim, bristol meyers squibb, celgene, leo pharma, lilly, menlo, novartis, pfizer, sun pharma, ortho dermatologics, and verrica. phoebe rich has received research and educational grants from abbvie, allergan, anacor pharmaceuticals, boehringer ingelheim, cassiopea, dermira, eli lilly, galderma, janssen ortho inc., kadmon corporation, leo pharma, merck, moberg derma, novartis, pfizer, ranbaxy laboratories limited, sandoz, viamet pharmaceutical inc., innovation pharmaceuticals (cellceutix), and cutanea life sciences. introduction • hyperhidrosis is a chronic medical condition characterized by excess sweat production beyond that which is necessary to maintain thermal homeostasis, affecting an estimated 4.8% of the united states (us) population1 • the condition has reportedly been associated with impacts on health‑related quality of life, social and emotional stress, and a relatively high risk of concomitant depression and anxiety2‑5 • real‑world observational data are limited in patients with hyperhidrosis, suggesting that additional research is warranted objectives • to describe clinical characteristics and treatment patterns of patients with hyperhidrosis • to determine the prevalence of depression and anxiety among patients with hyperhidrosis relative to patients in a control cohort • to examine health care resource utilization (hcru) and costs associated with concomitant depression and/or anxiety in patients with hyperhidrosis methods patient selection • patients were identified from january 2010 through november 2017 from the optum research database, a de‑identified database that contains medical and pharmacy information for commercial and medicare advantage claims • inclusion criteria for patients newly diagnosed with hyperhidrosis were – commercial health plan members with continuous enrollment with medical and pharmacy coverage for 12 months before (the baseline or pre‑index period) and ≥12 months after the index date (follow‑up period) – ≥2 hyperhidrosis diagnosis codes and/or prescription claims for extra‑ or prescription‑strength antiperspirant; the index date was the first observed claim indicating hyperhidrosis – no claims for medical procedures (botulinum toxin a, microwave thermolysis, suction curettage, iontophoresis, endoscopic thoracic sympathectomy) with codes specific to hyperhidrosis treatment during the baseline period – no claims for the above medical procedures or pharmacy claims for oral systemic therapies not specific to hyperhidrosis treatment within 7 days of the index date • patients in the hyperhidrosis cohort were followed for a variable period of ≥12 months • a control cohort (cc) was constructed with comparable index year, age, gender, and health plan region to the hyperhidrosis cohort, and had the following key inclusion criteria – no evidence of hyperhidrosis based on medical claims or pharmacy claims for prescription‑strength antiperspirants – continuous enrollment criteria identical to that of the hyperhidrosis cohort • the index date for control cohort patients was selected as a random date of health care resource utilization during the identification period, such as an office visit, inpatient admission, or a prescription claim; patients were followed for a fixed 12‑month period beginning on the index date outcomes • outcome variables were – index year, age, gender, and geographic region – baseline comorbid conditions, defined using indicator variables for specific disease conditions based on international classification of disease (icd)‑9‑cm and icd‑10 diagnoses employed by the clinical classifications software, managed by the agency for healthcare research and quality – hyperhidrosis treatments (hyperhidrosis cohort only, variable follow‑up period) • these were determined by claims made during a variable follow‑up period for prescription‑strength antiperspirants, botulinum toxin a injections, oral systemic therapies, microwave thermolysis, suction curettage, iontophoresis, endoscopic thoracic sympathectomy, and/or glycopyrronium cloth – proportion of days covered (pdc), a measure of adherence to chronic medications (hyperhidrosis cohort only) • pdc was calculated for the first 12 months of follow‑up by dividing the number of days on which medication was available based on filled prescriptions by the number of days between the earliest prescription claim in the observation period through the end of the observation period (i.e., twelve months of follow‑up) – depression and/or anxiety claims (hyperhidrosis and control cohort, 12‑month follow‑up period) • depression was defined as ≥1 medical claim with a diagnosis code for depression in any position and/or ≥1 pharmacy claim for a medication indicated specifically as an antidepressant • anxiety was defined as ≥1 medical claim with a diagnosis code for anxiety in any position and/or ≥1 pharmacy claim for a medication indicated specifically as an anxiolytic • depression and/or anxiety was defined as above while also including patients without a diagnosis code for depression or anxiety but with ≥1 pharmacy claim for a medication indicated for the treatment of both depression and anxiety • second indicator variables identified patients with new depression, anxiety, and depression and/or anxiety (claims that were not identified during the pre‑index period) – all‑cause hcru within the hyperhidrosis cohort; patients with ≥1 ambulatory visit, ≥1 emergency department (er visit), or ≥1 inpatient stay during follow‑up were identified, and each type of encounter was counted – all‑cause health care costs within the hyperhidrosis cohort, calculated as combined health plan and patient paid amounts; costs were inflation‑adjusted to 2018 dollars using the annual medical care component of the consumer price index analysis • all variables were analyzed descriptively • the occurrence, counts, and time until treatments were summarized; to account for variable follow‑up, binary indicators of treatments and counts of the number of treatments were also presented as incidence rates, with rates per person‑year, the number of events (i.e., patients who had the treatment), and the number of person‑years; a kaplan‑meier analysis of the time until the first use of each treatment (the “event”) for all patients as a function of time was also performed • a multivariable logistic regression model examined the presence of depression/anxiety in the patient cohort while controlling for patient characteristics including gender, age, and geographic region, any post‑index hyperhidrosis treatment, and five common comorbidities (respiratory infections, other lower respiratory infections, other upper respiratory infections, other gastrointestinal disorders, and other skin conditions) identified by the ahrq software6 in this sample • comparisons between cohorts were performed with t‑tests or chi‑square statistics, as appropriate • p values were computed with clustering to account for dependence between subjects due to matching; z‑tests using robust standard errors in an ordinary least squares regression were used for continuous measures, and rao‑scott tests were used for binary measures • depression and anxiety claims were summarized for the baseline period, the total follow‑up period, and new claims made only during the follow‑up period results sample selection • of 309,709 individuals identified with at least 1 claim for a prescription‑strength antiperspirant or an icd code for hyperhidrosis, 44,484 patients met selection criteria for inclusion in the hyperhidrosis cohort; the control cohort was comprised of 137,451 patients patient characteristics • patients in the hyperhidrosis cohort were a mean age of 36.5 ± 16.5 years (cc=40.2 ± 16.9); 83.5% were ≥18 years of age (cc=87.8%), and 58.5% were female (cc=56.0%) • the baseline comorbid conditions that showed the greatest difference in frequency between the hyperhidrosis and control cohorts were respiratory infections (39.0% hyperhidrosis vs. 30.7% control) and other skin disorders (30.9% hyperhidrosis vs 20.5% control) (table 1) – acne (9%), rash and other non‑specific skin eruption (3%), and actinic keratosis (3%) were the most common comorbid skin disorders in the hyperhidrosis cohort (cc= 6%, 3%, and 3%, respectively) table 1. common patient comorbidities at baseline ahrq comorbidities hyperhidrosis cohort (n=44,484) control cohort (n=137,451) respiratory infections n 17,330 42,227 % 38.96 30.72 other skin disorders n 13,734 28,187 % 30.87 20.51 other connective tissue disease n 12,745 33,509 % 28.65 24.38 disorders of lipid metabolism n 8,929 29,148 % 20.07 21.21 non‑traumatic joint disorders n 10,623 29,874 % 23.88 21.73 spondylosis; intervertebral disc disorders; other back problems n 10,338 27,537 % 23.24 20.03 diseases of female genital organs n 9,685 25,605 % 21.77 18.63 eye disorders n 9,179 26,153 % 20.63 19.03 other lower respiratory disease n 8,840 20,785 % 19.87 15.12 hypertension n 8,220 27,769 % 18.48 20.20 all comorbid conditions listed were significantly higher in the hyperhidrosis vs control cohort (p<0.001) except disorders of lipid metabolism and hypertension, which were significantly higher in the control cohort (p<0.001) as sample sizes were large, statistical significance was easily achieved due to overpowering. p values were computed with clustering; rao‑scott test was used for binary measures comorbidities were identified by clinical classification software for icd‑9‑cm/icd‑10‑cm codes from the ahrq ahrq, agency for healthcare research and quality; icd, international classification of disease treatment patterns • a slight majority of patients in the hyperhidrosis cohort (51.6%) received treatment with prescription antiperspirants, while 13.1% had prescription fills for oral systemic therapies; a very small percentage of the hyperhidrosis sample received procedures for hyperhidrosis treatment, including botulinum toxin a (figure 1) • prescription antiperspirants were the earliest initiated therapies in the hyperhidrosis cohort during the variable follow‑up period, with a mean ± sd time to first prescription fill of 1.4 ± 6.3 months (table 2); this is consistent with the international hyperhidrosis society (ihhs) clinical treatment algorithm, which generally recommends antiperspirants as a first line of therapy for hyperhidrosis – while glycopyrronium cloth is also recommended by the ihhs as a first line treatment for primary axillary hyperhidrosis, the therapy was not available in the us until october 2018; since the study included data through november 2018, there were very few prescriptions made for glycopyrronium cloth (n=6) in this dataset, precluding meaningful analysis of the treatment option • on average, other treatments were not initiated until over a year after the index date, including oral systemic therapies, which had a mean time to initiation of 16.9 ± 19.1 months (table 2) – these results were confirmed with kaplan‑meier analyses of adjusted time to treatments and procedures (figure 2) • the incidence rate shows the average frequency of treatment for patients in a given year; incidence rates adjusted for the variable follow‑up period ranged from 0.29 (endoscopic thoracic sympathectomy) to 1.80 (oral systemic therapies) per person years (table 2) • adherence to prescription medications was low over 12 months, with mean ± sd pdc of only 0.13 ± 0.09 for prescription antiperspirants and 0.30 ± 0.28 for oral systemic therapies (table 2) figure 1. treatments in the hyperhidrosis cohort 51.60 13.09 2.48 0.13 0.16 1.04 0.19 0 10 20 30 40 50 60 p er ce nt ag e of p at ie nt s r ec ei vi ng t h er ap y es/ps antiperspirants (n=22,954) oral systemic therapies (n=5,823) botulinum toxin a (n=1,104) microwave thermolysis (n=58) suction curettage (n=70) iontophoresis (n=463) endoscopic thoracic sympathectomy (n=85) es; extra strength; ps, prescription strength treatment categories are not mutually exclusive; percentages do not account for variable follow‑up period table 2. hyperhidrosis cohort (n=44,484) therapies and procedures therapy or procedure time to first occurrence of therapy /procedure (months), mean (sd)a incidence rates proportion of days covered (pdc)b , mean (sd)events person years rate per person years prescription‑strength antiperspirants (n=22,954) 1.4 (6.3) 57,756 83,472 0.69 0.13 (0.09) oral systemic therapies (n=5,823) 16.9 (19.1) 40,965 22,709 1.80 0.30 (0.28) botulinum toxin a (n=1,104) 15.1 (19.5) 3,683 4,530 0.81 microwave thermolysis (n=58) 19.9 (17.8) 379 239 1.59 suction curettage (n=70) 19.7 (18.2) 105 279 0.38 iontophoresis (n=463) 22.9 (20.8) 1,733 2,097 0.83 endoscopic thoracic sympathectomy (n=85) 15.0 (21.8) 98 338 0.29 atimes do not account for variable follow‑up period within sample bproportion of days covered (pdc) was calculated for prescription medications and/or prescription‑strength antiperspirants only f igure 2. kaplan‑meier analysis of adjusted time to treatments and procedures 40% 50% 60% 70% 80% 90% 100% 0 6 12 24 36 48 60 72 84 96 p ro p or ti on o f p at ie nt s u nt re at ed endoscopic thoracic sympathectomy iontophoresis botulinum toxin a injection oral systemic therapies extraor prescription-strength antiperspirant time to treatment (months) glycopyrronium cloth, microwave thermolysis, and suction curettage were also measured; very few patients had these treatments and their trend lines are therefore not shown log‑rank test was used for assessing equality of survival distributions emotional health characteristics • the percentage of patients with depression or anxiety (figure 3) during the 12‑month baseline (pre‑index) period was 35% in the hyperhidrosis cohort (cc=26%, p<0.001) • this percentage increased during the 12‑month follow‑up period, with a significantly higher percentage of patients in the hyperhidrosis cohort with reports of depression or anxiety than in the control group (41.1% vs 28.2%, p<0.001), as well as with newly diagnosed depression or anxiety (18.2% vs 10.6%, p<0.001) • patients in the hyperhidrosis cohort had nearly 1.8 times higher odds of depression or anxiety than those in the control cohort while controlling for other variables (odds ratio=1.76, 95% confidence interval 1.7‑1.8, p<0.001; table 3) • older patients, females, and subjects with comorbid conditions, particularly gastrointestinal disorders, were more likely to experience depression or anxiety (table 3) figure 3. patients with depression and/or anxiety during pre‑index and follow‑up periods 0.0 10.0 20.0 30.0 40.0 50.0 p er ce nt ag e of p at ie nt s depression anxiety depression or anxiety 18.4 13.0 * 21.6 14.3 * 27.8 17.4 * 35.2 26.0 * 41.1 28.2 * 22.4 15.9 * 12-mo follow-uppre-index 12-mo follow-uppre-index 12-mo follow-uppre-index hyperhidrosis control *p<0.001 p values were computed with clustering; rao‑scott test was used for binary measures table 3. logistic regression model of 12‑month post‑index depression or anxiety independent variables post‑index depression or anxiety odds ratio lower 95% ci upper 95% ci p value hyperhidrosis cohort 1.756 1.715 1.798 <0.001 ahrq comorbidities respiratory infections 1.278 1.249 1.308 <0.001 other lower respiratory infections 1.434 1.395 1.475 <0.001 other upper respiratory infections 1.242 1.207 1.279 <0.001 other gastrointestinal disorders 1.824 1.767 1.882 <0.001 other skin conditions 1.197 1.168 1.226 <0.001 gender female 1.751 1.714 1.789 <0.001 male ref. – – – age <9 0.160 0.136 0.189 <0.001 9‑17 0.368 0.355 0.382 <0.001 18‑24 0.643 0.621 0.665 <0.001 25‑34 0.781 0.758 0.804 <0.001 35+ ref. – – – observations read = 181,935, observations used= 181,935 ahrq, agency for healthcare research and quality; ci, confidence interval depression, anxiety, health care costs, and utilization among patients with hyperhidrosis in a real‑world database analysis m. hull,1* k.k. gillard,2 j. peterson‑brandt,1 s.z. klein3 1optuminsight life sciences, eden prairie, mn, usa; 2dermira, inc., a wholly‑owned subsidiary of eli lilly and company, menlo park, ca, usa; 3university of utah hospital, salt lake city, ut, usa *michael hull was an employee of optum at the time the study was conducted poster presented virtually at the fall clinical dermatology conference • october 29 ‑ november 1, 2020 healthcare costs and hcru • while the distribution pattern of costs within the hyperhidrosis cohort was similar between patients with depression/anxiety and those without, patients with depression/anxiety had significantly higher mean [median] all‑cause total costs ($1905 [$636] vs $673 [$197]; p<0.001, and all‑cause medical costs ($1598 [$412] vs $544 [$127]; p<0.001) than those without depression/anxiety (figure 4a) – on average, ambulatory costs were the source of highest medical expense for patients both with and without depression/anxiety (figure 4b) figure 4. follow‑up health care costs within the hyperhidrosis cohort a. overall medical and pharmacy costs $636.24 $412.26 $99.74 $197.17 $126.89 $24.73 0 400 800 1200 1600 2000 total costs (medical + pharmacy) medical costs pharmacy costs m ed ia n c os t (i q r ) u s $ depression/ anxiety (n=18,266) nondepression/ anxiety (n=26,218) depression/ anxiety (n=18,266) nondepression/ anxiety (n=26,218) depression/ anxiety (n=18,266) nondepression/ anxiety (n=26,218) mean $1,905.39 $672.91 $1,598.12 $543.92 $307.28 $128.99 sd $5,050.82 $2,202.78 $4,865.60 $2,015.12 $739.93 $633.40 depression/anxiety patients (n=18,266) non-depression/anxiety patients (n=26,218) p<0.001 for all comparisons between patients with and without depression/anxiety based on mean values iqr, interquartile range b. medical costs by encounter $0 $0 $15.62 $319.10 $105.87 $0 $0 $3.73 $0.00 $400.00 $800.00 ambulatory costs emergency room costs inpatient costs other medical costs m ed ia n c os t (i q r ) u s $ depression/ anxiety (n=18,266) non depression/ anxiety (n=26,218) depression/ anxiety (n=18,266) non depression/ anxiety (n=26,218) depression/ anxiety (n=18,266) nondepression/ anxiety (n=26,218) depression/ anxiety (n=18,266) nondepression/ anxiety (n=26,218) mean $940.41 $360.40 $39.29 $13.26 $481.20 $122.69 $137.22 $47.58 sd $2,411.34 $1,219.50 $222.33 $62.64 $3,057.61 $1,060.43 $789.99 $539.02 depression/anxiety patients (n=18,266) non-depression/anxiety patients (n=26,218) $0 $0 $15.62 $319.10 $105.87 $0 $0 $3.73 $0.00 $400.00 $800.00 ambulatory costs emergency room costs inpatient costs other medical costs m ed ia n c os t (i q r ) u s $ depression/ anxiety (n=18,266) non depression/ anxiety (n=26,218) depression/ anxiety (n=18,266) non depression/ anxiety (n=26,218) depression/ anxiety (n=18,266) nondepression/ anxiety (n=26,218) depression/ anxiety (n=18,266) nondepression/ anxiety (n=26,218) mean $940.41 $360.40 $39.29 $13.26 $481.20 $122.69 $137.22 $47.58 sd $2,411.34 $1,219.50 $222.33 $62.64 $3,057.61 $1,060.43 $789.99 $539.02 depression/anxiety patients (n=18,266) non-depression/anxiety patients (n=26,218) p<0.001 for all comparisons between patients with and without depression/anxiety based on mean values; iqr, interquartile range • a significantly higher percentage of patients with depression/anxiety had an inpatient stay (12.9% vs 4.8%; p<0.001) and emergency room visit (43.3% vs 26.0%; p<0.001) when compared with patients who did not have depression/anxiety (figure 5) figure 5. follow‑up health care resource utilization within the hyperhidrosis cohort 99.8 98.6 43.3 26.0 12.9 4.8 0 20 40 60 80 100 120 ambulatory visit emergency room visit inpatient visit depression/anxiety patients (n=18,266) non-depression/anxiety patients (n=26,218) p er ce nt ag e of p at ie nt s all patient comparisons were significant at p<0.001 limitations • acknowledging that errors may occur with diagnosis codes and claims, the risk of misidentifying hyperhidrosis was mitigated by the requirement of at least two claims indicating the condition for patient study inclusion; identification of depression or anxiety required a single claim • codes for procedures and oral systemic therapies were generally not specific to the treatment of hyperhidrosis; this was addressed by excluding patients with non‑specific codes for these procedures or pharmacy codes for oral systemic therapies within seven days before or after the index date – however, all instances of these procedures and medications (codes for botulinum toxin a, microwave thermolysis, suction curettage, iontophoresis, endoscopic thoracic sympathectomy, and pharmacy codes for oral systemic therapies) were counted in the follow‑up period, which may have led to an overestimation of the frequency of the procedures used for hyperhidrosis treatment • results and conclusions are limited to patients enrolled in managed care plans accessible from the optum research database and may not be generalizable to other commercially insured populations in the us • prescriptions filled outside the pharmacy benefit (out‑of‑pocket), drug samples, and over‑the‑counter medications were not captured, which could potentially overestimate the proportion of untreated patients; this is of particular note since over‑the‑counter antiperspirants may be appropriate for some hyperhidrosis patients • counts and percentages of treatments and procedures used, as well as mean time to first receipt of treatments do not account for censoring; incidence rates, along with kaplan‑meier analyses of adjusted time to treatment were included to address the variable follow‑up period • the potential relationship between treatment of hyperhidrosis and a diagnosis of depression and/or anxiety was not assessed, and the observational study design precludes causal assessment of the relationship between hyperhidrosis and anxiety and/or depression • there may be confounding variables other than the presence of anxiety and depression that could have driven the differences in hcru and costs; multivariable regression analysis was not conducted, and the relationship between depression or anxiety and outcomes is further confounded because depression/anxiety cohort assignment was based on follow‑up diagnoses conclusions • this real‑world observational data analysis shows that substantial comorbid depression and anxiety exist among patients in a hyperhidrosis cohort relative to a control group, both prior to and following diagnosis of hyperhidrosis or following a prescription for excessive sweating – other comorbidities at baseline (eg, respiratory conditions and other skin conditions) were more common in the hyperhidrosis cohort, which may underlie some differential patterns of healthcare resource utilization relative to the control cohort • adherence (defined by proportion of days covered) to prescription antiperspirants and oral systemic therapies was poor, suggesting that tolerability and efficacy may be limiting factors to effective treatment of hyperhidrosis • in patients with hyperhidrosis, all‑cause health care costs and hcru were significantly higher in those who experienced depression/anxiety when compared to those without depression/anxiety • these results demonstrate higher overall health care burden for the hyperhidrosis patient population • further research and provider attention are needed to elucidate the emotional burden experienced by patients following a diagnosis of hyperhidrosis references 1. doolittle j, walker p, mills t, thurston j. hyperhidrosis: an update on prevalence and severity in the united states. arch dermatol res 2016; 308(10):743‑749. 2. smith cc, pariser d. primary focal hyperhidrosis. up‑to‑date 2018: https://www.uptodate.com/contents/ primary‑focal‑hyperhidrosis?search=hyperhidrosis&source=search_ result&selectedtitle=1~150&usage_ type=default&display_rank=1. 3. bahar r, zhou p, liu y, huang y, et al. the prevalence of anxiety and depression in patients with or without hyperhidrosis (hh). j am acad dermatol. 2016;75:1126‑1133. 4. braganca gm, lima so, pinto neto af, et al. evaluation of anxiety and depression prevalence in patients with primary severe hyperhidrosis. an bras dermatol. 2014;89(2):230‑235. 5. kamudoni p, mueller b, halford j, schouveller a, stacey b, salek ms. the impact of hyperhidrosis on patients’ daily life and quality of life: a qualitative investigation. health qual life outcomes. 2017;15(1):121. 6. clinical classification software (ccs) for icd‑9‑cm/icd‑10‑cm. agency for healthcare research and quality, rockville, md. www.hcup‑us.ahrq.gov/toolssoftware/ccs/ccs.jsp acknowledgements this study and all costs associated with development of this poster were funded by dermira, inc., a wholly‑owned subsidiary of eli lilly and company. medical writing support was provided by prescott medical communications group (chicago, il). disclosures szk: employed by dermira as a consultant; kkg: employee of dermira, inc., a wholly‑owned subsidiary of eli lilly and company; mh: employee of optum at the time study was conducted, which received funding for this research; jpb: employee of optum, which received funding for this research emmy graber,1 hilary baldwin,2 julie c. harper,3 linda stein gold,4 andrew f. alexis,5 richard g. fried,6 evan a rieder,7 james del rosso,8 leon kircik,9 siva narayanan,10 volker koscielny,11 ismail kasujee,11 adelaide hebert12 1the dermatology institute of boston and northeastern university, boston, ma; 2acne treatment and research center, brooklyn, ny; 3the dermatology and skin care center of birmingham, birmingham, al; 4henry ford health system, bloomfield, mi; 5weill cornell medical college, new york, ny; 6yardley dermatology associates, yardley, pa; 7new york university grossman school of medicine, new york, ny; 8jdr dermatology research/thomas dermatology, las vegas, nv; 9icahn school of medicine, mount sinai, new york, ny, 10avant health llc, bethesda, md; 11almirall sa, barcelona, spain; 12uthealth mcgovern medical school, houston, tx. investigator global assessment (iga) of acne vulgaris and iga success among patients with moderate to severe non-nodular acne vulgaris (av) administered sarecycline in community practices across the u.s: proses study analysis by gender and age introduction: the objective of this analysis was to evaluate facial iga and the associated iga success, stratified by age and gender, among av patients administered sarecycline in community practices across the u.s. methods: a single-arm, prospective cohort study (proses) was conducted with moderate-to-severe nonnodular av patients >9 years who were prescribed sarecycline in real-world community practices in the us. facial iga of av status was collected on a five-point adjectival response scale (0(clear)-4(severe)). iga success at week-12 was defined as >2-grade improvement and score 0-clear or 1-almost clear at week-12. proportion of patients achieving iga success was analyzed, stratified by gender and age (9-17yrs, >=18yrs). results: a total of 253 av patients completed the study (female: 66.40%; 9-17yrs: 39.92%; >=18yrs: 60.08%; facial iga success at week-12 was 56.47% for male and 60.12% for female; 57.43% for patients 9-17yrs old and 59.87% for patients >=18yrs old. conclusion: within the study cohort of adolescent and adult patients with moderate to severe av at baseline administered sarecycline, a narrow-spectrum, tetracycline-derived antibiotic for 12 weeks, across the gender and age groups, majority of patients achieved iga success at week-12. synopsis conclusions • within the study cohort of adolescent and adult patients with moderate to severe av at baseline administered sarecycline, a narrow-spectrum, tetracycline-derived antibiotic for 12 weeks, across the gender and age groups, majority of patients achieved iga success at week-12. sponsored by almirall, s.a. methods • a single-arm, prospective cohort study (proses) was conducted with moderate-to-severe non-nodular av patients ≥9 years who were prescribed sarecycline in real-world community practices in the us. • a total of 300 subjects were enrolled from 30 community practices across the u.s. • facial iga of av status was collected on a five-point adjectival response scale (0 (clear), 1 (almost-clear), 2 (mild), 3 (moderate), 4 (severe)) at baseline and weeks 4, 8 & 12. • iga success at week-12 was defined as ≥2-grade improvement and score 0-clear or 1-almost clear at week-12. • last observation carried forward (locf) imputation was considered for imputing missing data for the calculation of iga and iga success; however, there was no missing data at week-12, within the analytic population. • proportion of patients achieving iga success was analyzed, stratified by gender and age (9-17yrs, ≥18yrs). objective • the objective of this analysis was to evaluate facial iga and the associated iga success, stratified by age and gender, among av patients administered sarecycline in community practices across the u.s. results table 2: patient demographics (n=253) demographic group proportion of patients age group, % pediatric (<18 yrs) 39.92 adult (≥18 yrs) 60.08 age group, mean pediatric (<18 yrs) 26.63 adult (≥18 yrs) 14.81 gender, % male 33.60 female 66.40 race,% white 66.80 other 15.81 black/african american 9.88 asian 5.93 prefer not to answer 3.16 american indian or alaskan 0.79 native hawaiian/pacific islander 0.40 ethnicity,% (hispanic, latino or of spanish origin) yes 33.99 no 66.01 baseline iga, % moderate 86.56 severe 13.44 • a total of 253 av patients completed the study at week-12 with 58.90% of patients achieving iga success by week-12. • the proportion of patients with an iga of clear/almost clear increased from 0% at baseline to 58.90% at week-12 (p<0.0001). proportion of patients with iga success stratified by gender and age group as shown in figures 1 & 2 receptively. • there was no statistically significant difference in iga success between genders and between age groups. results 0.00% 5.94% 27.72% 57.43% 0.00% 11.84% 38.16% 59.87% 0% 10% 20% 30% 40% 50% 60% 70% baseline week-4 week-8 week-12 p ro po rti on o f p at ie nt s figure 2: clinician acne evaluation of patient facial iga success: stratified by age group patients ≥ 9 and < 18 years (n=101) patients ≥ 18 years (n=152) 0.00% 5.88% 30.59% 56.47% 0.00% 10.71% 35.71% 60.12% 0% 10% 20% 30% 40% 50% 60% 70% baseline week-4 week-8 week-12 p ro po rti on o f p at ie nt s figure 1: clinician acne evaluation of patient facial iga success: stratified by gender male (n=85) female (n=168) table 1: site characteristics domain n=30 current workplace, % private, office-based practice 100.00 hospital-based practice 0.00 total number of board-certified dermatologists in the practice, % 3.10 at present, how many patients with acne vulgaris do you personally manage in a given month? mean 86.90 how long have you been practicing dermatology, post-residency? 19.30 how often do you prescribe broad-spectrum antibiotics (such as doxycycline and minocycline)? % never 0.00 rarely 3.33 some of the time 36.67 most of the time 33.33 all of the time 26.67 iga success iga success powerpoint presentation assessments ■ web-based questionnaires administered at baseline, weeks 2, 4, 8, 12, and 24 ■ patients were divided into mild (bsa <3%), moderate (bsa 3-10%), or severe (bsa>10%)3 real-world effectiveness of ixekizumab in mild, moderate, and severe psoriasis: the patient perspective key eligibility criteria ■ patients with psoriasis enrolled in the us ixekizumab csp ■ ≥18 years of age ■ commercial insurance ■ initiated ixekizumab within 7 days of screening ■ device with access to the internet alice b. gottlieb1, russel burge2, william n. malatestinic2, baojin zhu2, yunyang zhao2, julie mccormack3, miriam kimel3, meghan feely2, joseph f. merola4 1icahn school of medicine at mount sinai, new york, usa; 2eli lilly and company, indianapolis, usa; 3evidera, bethesda, usa; and 4harvard medical school, brigham and women’s hospital, boston, usa methods us ixekizumab csp design patient demographics and baseline characteristics references 1. liu l, et al. j inflamm res. 2016;9:39-50 2. kimball, et al. br j dermatol. 2016; 157-162 3. armstrong, et al. jama dermatol. 2013;149(10):1180–1185 psoriasis severity mild (n=180) moderate (n= 223) severe (n=120) age, mean ± sd 49.4 ± 12.0 47.0 ± 12.0 45.7 ± 11.8 women, n (%) 122 (68%) 139 (62%) 71 (59%) white, n (%) 150 (83%) 197 (88%) 104 (87%) bmi, kg/m2, mean ± sd 30.7 ± 6.7 32.1 ± 8.0 34.0 ± 8.6 duration from onset of psoriasis, months, mean ± sd 190.1 ± 172.2 185.3 ± 151.8 229.4 ± 184.1 psoriasis locations, n (%) scalp psoriasis 93 (52%) 135 (61%) 97 (81%) genital psoriasis 20 (11%) 50 (22%) 45 (38%) nail psoriasis 44 (24%) 57 (26%) 39 (33%) psoriatic arthritis, n (%) 120 (67%) 109 (49%) 58 (48%) bio-experienced (previous 2 years), n (%) 110 (61%) 97 (44%) 47 (39%) study was sponsored by eli lilly and company background ■ ixekizumab, a highly selective il17a monoclonal antibody, has been approved for the treatment of moderate to severe plaque psoriasis1 ■ there are limited real-world data available on patient-reported outcomes (pros) shortly after ixekizumab initiation, particularly among patients with mild psoriasis ■ data collection from the us ixekizumab customer support program (csp) aims to create a large, patient-reported us database to fill this information gap objective ■ this analysis evaluated the realworld effectiveness of ixekizumab, as measured by pros at baseline and week 24 among patients with mild, moderate, or severe psoriasis who were enrolled in the taltz csp – we assessed the overall sample and selected subgroups of clinical interest key results at baseline and week 24 discussion  improvement in all outcome measures were observed by week 24 across all severities of psoriasis − similar improvements were observed across the subgroups: biologic use, psa status, and pso nail involvement at baseline  with a real-world study population, factors influencing outcomes may include, but are not limited to, self-reported psoriasis, compliance with medications, and experience with biologics conclusions ■ in a real-world setting, pro improvements have been observed across all severities of psoriasis, with the greatest improvements observed in patients with severe psoriasis winter clinical dermatology conference (wcdc); kohala coast, usa; 13-18 january 2023 scan or click the qr code or use this url (https://lillyscience.lilly.com/congress/wcdc2023) for a list of all lilly content presented at the congress. other company and product names are trademarks of their respective owners. abbreviations bmi=body mass index; bsa=body surface area; csp=customer support program; dlqi=dermatology life quality index; ixe=ixekizumab; nrs=numeric rating scale; patga=patient’s global assessment; prepi=patient-reported extent of psoriasis involvement; pros=patient-reported outcomes; promis=patient-reported outcomes measurement information system; psa=psoriatic arthritis; pso=psoriasis; sd=standard deviation statistical analyses ■ pros were assessed through week 24 – evaluated percentage of patients with 0 or 1 scores at baseline and at week 24 for the dlqi, patga, itch nrs, and skin pain nrs ■ descriptive analyses with observed data ■ no data imputation was performed ■ data are reported for the overall study population and by bio-naïve and bio-experienced and by psoriatic arthritis subgroups ■ changes from baseline were evaluated with a mixed effects model ■ p-values are for within-group comparisons of responses at baseline and at week 24 itch nrs: percentage of patients with 0/1 scores dlqi: percentage of patients with 0/1 scoresbsa: mean % involvement skin pain nrs: percentage of patients with 0/1 scores p < 0.001 for all within-group comparisons of responses at baseline and at week 24 disclosures  a. b. gottlieb has received honoraria as an advisory board member, non-promotional speaker or consultant for: amgen, anaptysbio, avotres therapeutics, boehringer ingelheim, bristol myers squibb, dice therapeutics, dermavant, eli lilly, janssen, novartis, pfizer, sanofi, sun pharma, ucb pharma, and xbiotech (stock options for an ra project); research/educational grants from: anaptysbio, janssen, novartis, ortho dermatologics, sun pharma, bms, and ucb pharma; all funds go to the icahn school of medicine at mount sinai  r. burge, w. n. malatestinic, b. zhu, y. zhao, m. feely are shareholders and employees of: eli lilly and company; m. feely is a clinical instructor at: mount sinai hospital and has received consulting, travel, or speaker fees from: aerolase, castle biosciences, galderma aesthetics, glow recipe, la roche-posay l'oréal, revian, sonoma pharmaceuticals, sun pharma, and suneva medical; j. mccormack and m. kimel declare no conflicts of interest; j. f. merola is a consultant and/or investigator for: abbvie, amgen, biogen, bristol myers squibb, dermavant, eli lilly and company, janssen, leo pharma, novartis, pfizer, sanofi regeneron, sun pharma, and ucb pharma  this study was sponsored by eli lilly and company. medical writing services were provided by molly tomlin, ms, med, of eli lilly and company patga: percentage of patients with 0/1 scores mild (n=180) moderate (n= 223) severe (n=120) baseline week 24 baseline week 24 baseline week 24 overall 9.9 8.0 10.6 7.9 10.4 7.7 bio-naïve 9.3 7.6 10.0 7.2 10.2 7.8 bio-experienced 10.3 8.3 11.2 8.8 10.9 7.5 pso + psa 10.3 8.6 11.6 8.6 11.1 7.9 pso only 9.2 6.9 9.5 7.2 9.8 7.5 pso on nails 10.2 8.6 11.3 7.5 11.2 7.4 no pso on nails 9.9 7.8 10.3 8.1 10.1 7.8 promis sleep-related impairment total score*: mean values at baseline and at week 24 the scale for mild was changed to 0 to 20 to view changes from baseline to week 24 2 *measures self-reported perceptions of alertness, sleepiness, and tiredness during usual waking hours, and the perceived functional impairments during wakefulness associated with sleep problems/impaired alertness; 4 items on a scale from “not at all” (1) to “very much” (5) slide number 1 skin november 2017 volume 1 issue 3 copyright 2017 the national society for cutaneous medicine 117 original research impact of temperature on injection-related pain caused by subcutaneous administration of ustekinumab: a three-arm open-label randomized controlled trial yasaman mansouri md a,c , yasmin amir ba a , michelle min md msci a , raveena khanna ba a,d , ruiqi huang msci b , mayte suarez-farinas phd a,b , mark lebwohl md a departments of dermatology a , population health science and policy b , icahn school of medicine at mount sinai, new york ny c metropolitan hospital center, new york, ny d creighton university school of medicine, omaha ne abstract background: adherence to subcutaneous biologic agents for the treatment of psoriasis can be negatively influenced by injection pain. objective: to explore the differences in injection site pain when patients are pre-treated with heat or cold, versus no pre-treatment prior to administration of a subcutaneous biologic agent. methods: in an observational cohort study, patients receiving subcutaneous injections of ustekinumab were randomly assigned to receive pretreatment with ice, heat, or no intervention over three visits. post-dose, patients rated pain on a 100 mm visual analogue scale (vas). results: there was an overall increase in the vas score for both heat (2.51, p=0.30) and ice (3.33, p=0.16), compared to no intervention. no differences were found between the two intervention groups (-0.83, p=0.73). on average, females had the same vas scores with ice compared to that of no intervention (-0.12, p=0.97) and a non–significant decrease of 3.29 points (p=0.38) with heat. males had increased pain scores by 5.65 points (p=0.07) with ice and by 6.39 points (p=0.04) with heat. limitations: pain is a subjective measurement and objective quantification is difficult. conclusions: on average, neither heat nor cold application reliably reduced pain. our results do not support the application of heat or cold prior to ustekinumab injection. skin november 2017 volume 1 issue 3 copyright 2017 the national society for cutaneous medicine 118 our improved understanding of the immune pathways involved in various skin diseases has allowed us to use more targeted therapeutics such as biologic agents. however, the long-term efficacy of these medications is directly dependent upon the degree of patient compliance and medication adherence. 1 while usually welltolerated, most biologic agents are injectable drugs. the subcutaneous injections can be painful, and fear of the needle can be a real issue, and may even prevent some patients from undergoing treatment with a biologic agent. 2 adherence thus is greatly influenced by fear of needles, as well as pain from injection administration. 2 in fact, previous studies have noted that injection-related pain and discomfort alone can lead to discontinuation of medications. 3 in a recent population-based multinational assessment of psoriasis and psoriatic arthritis, anxiety and fear related to injections and side effects were the most common reason for finding injectable biologics burdensome, with 10% of patients reporting pain and discomfort caused. 4 therefore, reduction in injection-site pain could potentially result in improved adherence with better outcomes and patient satisfaction. methods of reducing pain from injections are thus appealing to both patients and practitioners. various methods can be used prior to needle injection to ease the discomfort. the use of icing or cooling the skin is the most commonly reported intervention to reduce pain, and is being used prior to various interventions, such as physical therapy, laser treatment, and minor surgical procedures. the use of skin cooling has been reported to be successful in reducing pain from various injections, such as goserelin, 5 local anesthesia, botulinum toxin, and intralesional steroid injection, 6-10 local anesthesia injections during dental procedures, 11 and heparin injections. 12 other reported methods include vibration anesthesia. 13-14 warming the injected product has been reported, especially with local anesthetics. 15-17 pain is a subjective experience and can be difficult to measure. various methods have been used in experimental studies, with the visual analogue scale (vas) being the preferred approach. 18-19 the vas is a commonly used outcome to assess the degree of pain a patient experiences. 18-20 a horizontal line measuring 100 millimeters is used to represent the degree of pain. the left end of the line represents “no pain at all”, while the right end represents “worst pain imaginable”. in clinical studies, the patient documents pain intensity by depicting a vertical line that bisects the scale. the vas is a well-validated scale for characterizing the degree of pain associated with a specific intervention. 18+20 here we aimed to investigate whether the application of either heat or cold prior to an injection would be associated with lower pain scores, when compared to no pretreatment. as the conditions requiring biologic use are chronic illnesses with negative impact on health-related quality of life, it becomes imperative to define ways to reduce administration discomfort and increase compliance. more specifically, we aimed to use the vas to assess whether pre-treatment with heat or cold would reduce injection site pain, versus no pre-injection intervention at all prior to administration of a subcutaneous biologic agent. introduction skin november 2017 volume 1 issue 3 copyright 2017 the national society for cutaneous medicine 119 study design in this three-arm crossover open-label randomized controlled trial, we enrolled adults receiving treatment with the subcutaneous biologic agent ustekinumab at the mount sinai medical centre in new york, ny. prior to beginning this study, approval for all study related documents was obtained from the mount sinai school of medicine program for the protection of human subjects (institutional review board). patient demographics, medical history, and treatments were obtained through medical records. patients provided written informed consent. to be eligible for the study, patients were required to be receiving treatment with a subcutaneous biologic agent. our initial aim was to include patients receiving any of the approved subcutaneous biologics. however, contrary to the other agents, which are selfadministered at home, ustekinumab is administered in the office, and it was therefore easier for us to recruit patients on ustekinumab. exclusion criteria were cold-, heat-, or pressure-induced urticaria, and analgesic use within 12 hours of their injection. our aim was to enroll a maximum of 200 subjects, to allow for a ten percent attrition rate, with a target of 100 patients completing the study. each patient required three study visits. patients were randomly assigned the order of intervention received (1/3 received ice first, 1/3 received heat first, 1/3 received no intervention first; the same randomization ratio applied for the second and third injections). randomization was performed using the second generator from www.randomization.com, where each subject must receive all the treatments in random order. the first patient was enrolled in the study in may 2014, while there was a delay in the trial registration on the clinicaltrials.gov website, which occurred in june 2014. only the first visit of the first study subject occurred prior to study registration (figure 1). patients then either received no pre-injection intervention, pre-injection intervention with ice, or pre-injection intervention with heating packs prior to administration of their subcutaneous biologic therapy. immediately post-dose, patients were asked to rate pain associated with the injection using a 100 mm vas pain score, which was described from 0 mm (no pain at all) to 100 mm (worst pain imaginable). this randomization aimed to reduce error in pain score measurement that may result if the order of pre-injection intervention was always the same (e.g. no intervention always first). interval level data were obtained by measuring the distance from the low end of each scale to the subject’s marked vas. pre-injection intervention included an ice pack covered by a disposable paper drape and placed against the skin for 2-3 minutes prior to injection, a reusable heating pack that was heated in the microwave for 45 seconds, covered by a disposable paper drape, and then applied to the skin for 2-3 minutes, or no pre-treatment prior to the injection. two investigators administered the drug injections, while one patient requested on injecting himself. methods skin november 2017 volume 1 issue 3 copyright 2017 the national society for cutaneous medicine 120 endpoints the primary endpoint for this study was the difference in the pain visual analogue scale (vas) scores between heat and cold pretreatment as compared to no pre-treatment prior to ustekinumab injection. we hypothesized that pre-treatment with either heat or cold would reduce the pain scores when compared to no pre-treatment prior to ustekinumab injection. statistical analysis sample size: as there were no preliminary data to base the sample size calculations on, the sample size was determined based on enrolment feasibility in our department. a sample size of 100 patients would have been adequate to detect moderated effect sizes (es= 0.28), with >80% power on a 2sided paired t-test. descriptive analysis was carried out to characterize the cohort in terms of demographic information. mean and standard deviation (sd) were calculated for continuous variables, along with median and interquartile range (iqr). count and percentages were calculated for categorical outcomes. one-way analysis of variance (anova) was used for the mean difference of age and vas scores across the three different intervention groups. chi-square tests were conducted to test the association between the categorical variables (gender and injector) and the intervention group, respectively. the primary analysis was to assess the efficacy of the pre-injection intervention (ice or heat) effect. a linear mixed-effect model was applied to take fixed effects (any potential covariates) and random effects (subject) into account, while also taking into account the correlation of different measurements for the same patient. the mixed model we applied is more advanced and adequate than other approaches (such as t test or anova) in this study since it can take three measurements into account and use as much information as possible in the presence of missing values. based on the likelihood ratio test and the akaike information criteria, the final model was fitted with an unstructured correlation and assuming homoscedastic within-group errors. according to the protocol, we primarily assessed the model with only the intervention group as the fixed effect. in an unplanned analysis,, we included all potential covariates (age, gender, time, injector) and their interaction with intervention in a multivariate linear mixed model and performed a step-wise backward selection algorithm to define the final model. interaction was also considered if appropriate. the final model identified by the backward selection algorithm included intervention, gender and the genderintervention interaction. no missing values were imputed in this analysis and all available data was used. patient characteristics a total of 118 patients currently on treatment were enrolled in the study, with 107 completing all three injections, ten patients receiving two injections, and one patient receiving only one injection (figure 1). the majority of these patients were receiving treatment for psoriasis, with a small number being treated for other skin disease. all available data were included in the primary analysis. the average age was 51.16 years (range 22-86, sd=16.37), and 41% were female. for this cohort, pain vas was 18.7 (sd=20.8) 107 patients received all three results skin november 2017 volume 1 issue 3 copyright 2017 the national society for cutaneous medicine 121 injections, 10 patients received two, and one patient received only one injection. one patient moved away, another stopped the drug due to poor efficacy, and the remaining 9 dropped out of the study due to scheduling difficulties. site of injection was the upper arm. the box plot indicated similarities of vas scores in different intervention groups, in terms of their median and iqr (figure 2a). safety endpoints in terms of safety and side effects related to ice or heating packs, none of the patients reported any clinically significant side effects. efficacy endpoints the primary efficacy endpoint for this study was the vas score. to assess the effect of the intervention on the vas score, a linear mixed-effect model was fitted considering treatment as fixed effect and a random intercept for each patient (figure 2b). results, summarized in table 1 showed an overall increase in the vas score for both heat (2.51, p=0.30) and ice (3.33, p=0.16) intervention. no differences were found between the two intervention groups (-0.83, p=0.73). to study the effect of the recorded variables in the analysis, we modelled the vas score including all the potential covariates and their interactions with the interventions in the model as fixed effects. model selection used a stepwise backward selection, with only intervention and gender (and its interaction) remaining in the model (table 2 and figure 2d). the distribution of the vas scores by gender (figure 2c) indicated that female patients had twice the pain scores than males even with no intervention (24.05 vs. 11.85, p=0.002). our model indicated that on average, female patients had the same vas scores when treated with ice compared to that of those with no intervention (-0.12, p=0.97), and a small, non–significant decrease of 3.29 points in the pain scores was observed (p=0.38) while applying heat pre-injection. on the contrary, male patients increased their pain scores by 5.65 points (p=0.07) with ice and by 6.39 points (p=0.04) with heat. of note, no significant differences between the effects of ice and heat were found in either gender group. we also compared the proportion of patients that decrease, have no change or increase the pain score in the pre-treatment group from non-intervention (table 3). results largely agree with the analysis of continuous vas scores with a larger percentage of females reporting a decrease in pain scores than males (42.86% in females vs. 36.92% in males for ice, and 45.24% in females vs. 33.85% in males for heat). these associations were not statistically significant (p=0.805 and p=0.342 for ice and heat, respectively). skin november 2017 volume 1 issue 3 copyright 2017 the national society for cutaneous medicine 122 figure 1: subject flow diagram figure 2: pain perception with subcutaneous injection of ustekinumab by intervention first randomized by (a,b), and stratified by gender (c,d) enrolled (n=118) and randomly assigned to order of intervention lost to follow-up after two injections (one patient moved away, one patient found the drug inefective and discontinued it and 8 patients had scheduling difficulties) (n=10) completed study (n=107) lost to follow-up after one injection (due to scheduling difficulties) (n=1) analyzed (n=118) skin november 2017 volume 1 issue 3 copyright 2017 the national society for cutaneous medicine 123 table 1. primary efficacy analysis for the vas score intervention ls-mean (estimated mean) sem lower ci upper ci p-value* none 16.78 1.95 12.9 20.6 ice 20.12 1.93 16.3 23.9 0.16 heat 19.29 1.96 15.4 23.2 0.30 treatment effect intervention ls-mean (estimated mean) sem lower ci upper ci p-value* heat-none 2.51 2.40 -2.2 7.2 0.30 ice-none 3.33 2.38 -1.4 8.0 0.16 heat-ice -0.83 2.39 -5.5 3.9 0.73 notes: * p-values comparing the mean for each group with the reference group (female, none) # p-values for gender effect, ice intervention effect, ice and gender interaction, heat intervention effect, heat and gender interaction. estimated means are the least square means estimated for each contrast, sem is the standard error of the mean, ci: lower and upper bound for the 95% confidence interval table 2. model with covariates (selection was based on backward model selection) intervention sex estimated mean sem lower ci upper ci p-value * none f 24.05 3.02 18.07 30.03 none m 11.85 2.49 6.93 16.78 0.002 ice f 23.93 2.99 18.01 29.86 0.974 ice m 17.51 2.47 12.62 22.40 0.232 heat f 20.77 3.05 14.73 26.81 0.385 heat m 18.25 2.50 13.29 23.20 0.048 treatment effect treatment effect sex estimated mean sem lower ci upper ci p-value p-value# ice none f -0.12 3.72 -7.46 7.22 0.97 0.232 ice none m 5.65 3.07 -0.39 11.70 0.07 heat none f -3.29 3.77 -10.72 4.15 0.38 0.048 heat none m 6.39 3.09 0.31 12.48 0.04 notes: * p-values comparing the mean for each group with the reference group (female, none) § p-values for comparing the difference between the sex in the change of vas score for ice and heat intervention group. # p-values for gender effect, ice intervention effect, ice and gender interaction, heat intervention effect, heat and gender interaction. estimated means are the least square means estimated for each contrast, sem is the standard error of the mean, ci: lower and upper bound for the 95% confidence interval skin november 2017 volume 1 issue 3 copyright 2017 the national society for cutaneous medicine 124 table 3. contingency tables for change in vas score by gender in ice and heat group table of vas score change by sex ice %column sex heat %column sex f m total f m total increase 21 (50%) 35 (53.85%) 56 increase 19 (45.24%) 39 60.00 58 no change 3 (7.14%) 6 (9.23%) 9 no change 4 (9.52%) 4 6.15 8 decrease 18 (42.86%) 24 (36.92%) 42 decrease 19 (45.24%) 22 33.85 41 total 42 65 107 total 42 65 107 fisher’s exact p=0.805 fisher’s exact p=0.342 note: fisher’s exact test is used to assess the association of vas score change and gender in ice and heat intervention. a variety of studies in the literature report successful pain reduction by skin cooling. our study demonstrated reduced pain scores in women after warming the skin prior to injection of biologic agents, although these findings were not statistically significant. we found that gender was an important factor in patients' perception of pain during the injection of subcutaneous biologic agents. interestingly, there was an opposite effect in the pain perception amongst males (figure 2d), who reported a pain increase after application of heat packs (95% ci: 0.403-12.281; p=0.036), as well after application of ice packs (95% ci: -0.66-11.136, p=0.081). this may be either due to a lower pain threshold in females, or an under-reporting of pain in male subjects. while numerous studies have shown that pain perception, pain thresholds, the prevalence of chronic pain conditions, and response to analgesia differ amongst the genders, 21-27 these previous mentioned studies did not report such a marked difference between the sexes in pain perception after interventions to reduce injection-related pain. it is possible that the researchers did not take the subjects’ gender into account when analyzing the results. studies of cold-evoked pain found cold thresholds to be lower in hairy skin compared to glabrous skin, 25 which may be explained by anatomical differences between the skin sites such as increased thickness of the epidermis and decreased density of cold receptors in glabrous skin. this would, however, not explain the contrast in pain perception noted between men and women in our study. furthermore, kennard et al. failed to show an effect of skin thickness between men and women in pain thresholds. 26 a meta-analysis of gender differences in mechanically induced pain demonstrated lower pain thresholds and discussion/conclusions skin november 2017 volume 1 issue 3 copyright 2017 the national society for cutaneous medicine 125 lower tolerance to pain in women, with the largest differences seen in pressure-pain and electrical stimulation. 27 it has been suggested that the social norms may influence men into appearing more stoic and under-reporting, 28 especially in the presence of female researchers, 29 as was the case in our study. however, contradictory evidence has also been shown, such as a study that demonstrated lower pain thresholds in females following noxious heat stimuli, independent of the gender of the experimenter, 30 as well as a study that measured pupil diameter in response to pain, which is caused by sympathetic stimulation and is therefore not under conscious control by the patient. the results showed similar response in pupil dilation in both genders. 31 these conflicting reports highlight the complexity of pain sensitivity and make interpretation difficult. one possible explanation for the lack of pain reduction following heat and cold application in our study, as compared to previous reports, may be the different drug composition of biologics. the decision whether or not to offer a patient a method of pain reduction prior to the injection of subcutaneous biologics therefore needs to be made by the respective clinician in every particular patient, while weighing the pros and cons of the different available methods. in particular, the gender of the patient needs to be taken into consideration, as this can greatly affect pain perception. while the application of both heat and ice packs is simple, inexpensive and safe, on average, neither heat nor cold application reliably reduced pain. we also could not identify which patients would be more likely to respond to heat or cold, except that female patients would more likely experience pain reduction with heat compared to males, while males experienced increased pain after heat application. further research is required into pain caused by injectable therapeutics and pain reduction methods, while taking into account possible gender differences in pain perception, and the drug composition and properties. conflict of interest disclosures: dr. mayte suarezfarinas has received research grants from pfizer, quorum, and genisphere. dr. mark lebwohl is an employee of the mount sinai medical centre, which receives research funds from abgenomics, amgen, anacor, boehringer ingleheim, celgene, ferndale, lilly, janssen biotech, kadmon, leo pharmaceuticals, medimmune, novartis, pfizer, sun pharmaceuticals, and valeant. funding: none. corresponding author: yasaman mansouri, md, mrcp (uk) dermatology metropolitan hospital center 1901 first avenue new york, ny 10029 yamansouri@gmail.com disclosure: dr. mansouri’s research fellowship at the icahn school of medicine at mount sinai was supported by the geoffrey dowling fellowship, an award from the british association of dermatologists (united kingdom). references: 1. bluett j, morgan c, thurston l, et al. impact of inadequate adherence on response to subcutaneously administered anti-tumour necrosis factor drugs: results from the biologics in rheumatoid arthritis genetics and genomics study syndicate cohort. rheumatology (oxford). 2015; 54:494-9. doi: 10.1093/rheumatology/keu358. 2. betegnie al, gauchet a, lehmann a, et al. why do patients with chronic inflammatory rheumatic diseases discontinue their biologics? an assessment mailto:yamansouri@gmail.com skin november 2017 volume 1 issue 3 copyright 2017 the national society for cutaneous medicine 126 of patients’ adherence using a self-report questionnaire. j rheumatol. 2016; 43:72430. doi: 10.3899/jrheum.150414. 3. bolge sc, goren a, tandon n. reasons for discontinuation of subcutaneous biologic therapy in the treatment of rheumatoid arthritis: a patient perspective. patient prefer and adherence. 2015; 9:121–31. doi: 10.2147/ppa.s70834. 4. lebwohl mg, kavanaugh a, armstrong aw, van voorhees as. us perspectives in the management of psoriasis and psoriatic arthritis: patient and physician results from the population-based multinational assessment of psoriasis and psoriatic arthritis (mapp) survey. am j clin dermatol. 2016; 17:87-97. doi: 10.1007/s40257-015-0169-x. 5. kinoshita h, kawa g, hiura y, et al. effectiveness of skin icing in reducing pain associated with goserelin acetate injection. int j clin oncol. 2010; 15:472-5. doi: 10.1007/s10147-010-0095-0. 6. al-qarqaz f, al-aboosi m, al-shiyab d, et al. using cold air for reducing needleinjection pain. int j dermatol. 2012; 51:848-52. doi: 10.1111/j.13654632.2011.05383.x. 7. skiveren j1, kjaerby e, nordahl larsen h. cooling by frozen gel pack as pain relief during treatment of axillary hyperhidrosis with botulinum toxin a injections. acta derm venereol. 2008; 88:366-9. doi: 10.2340/00015555-0465. 8. leff dr, nortley m, dang v, et al. the effect of local cooling on pain perception during infiltration of local anaesthetic agents, a prospective randomised controlled trial. anaesthesia. 2007; 62:677-82. 9. kuwahara rt, skinner rb. emla versus ice as a topical anaesthetic. dermatol surg. 2001; 27:495-6. 10. bechara fg, sand m, altmeyer p, et al. skin cooling for botulinum toxin a injection in patients with focal axillary hyperhidrosis: a prospective, randomised, controlled study. ann plast surg. 2007;58(3):299302. 11. davoudi a, rismanchian m, akhavan a, et al. a brief review on the efficacy of different possible and nonpharmacological techniques in eliminating discomfort of local anaesthesia injection during dental procedures. anesth essays res. 2016; 10:13-6. doi: 10.4103/0259-1162.167846. 12. kuzu n, ucar h. the effect of cold on the occurrence of bruising, haematoma and pain at the injection site in subcutaneous low molecular weight heparin. int j nurs stud. 2001; 38:51-9. 13. smith kc, comite sl, balasubramanian s, et al. vibration anaesthesia: a noninvasive method of reducing discomfort prior to dermatologic procedures. dermatol online j. 2004; 10:1. 14. mally p, czyz cn, chan nj, et al. vibration anaesthesia for the reduction of pain with facial dermal filler injections. aesthetic plast surg. 2014; 38:413-8. doi: 10.1007/s00266-013-0264-4. 15. hogan me, vandervaart s, perampaladas k, et al. systematic review and metaanalysis of the effect of warming local anaesthetics on injection pain. ann emerg med. 2011; 58:86-98.e1. doi: 10.1016/j.annemergmed. 2010.12.001. 16. mader tj, playe sj, garb jl. reducing the pain of local anaesthetic infiltration: warming and buffering have a synergistic effect. ann emerg med. 1994; 23:550-4. 17. colaric kb, overton dt, moore k. pain reduction in lidocaine administration through buffering and warming. am j emerg med. 1998; 16:353-6. 18. scott j, huskisson ec. graphic representation of pain. pain. 1976; 2:17584. skin november 2017 volume 1 issue 3 copyright 2017 the national society for cutaneous medicine 127 19. ohnhaus ee, adler r. methodological problems in the measurement of pain: a comparison between the verbal rating scale and the visual analogue scale. pain. 1975; 1:379-84. 20. price dd, bush fm, long s, harkins sw. a comparison of pain measurement characteristics of visual analogue and simple numerical rating scales. pain. 1994; 56:217-26. 21. maurer aj, lissounov a, knezevic i, et al. pain and sex hormones: a review of current understanding. pain manag. 2016; 6:285-96. doi: 10.2217/pmt-2015-0002. 22. fillingim rb, king cd, ribeiro-dasilva mc, et al. sex, gender, and pain: a review of recent clinical and experimental findings. j pain. 2009; 10:447-85. doi: 10.1016/j.jpain.2008.12.001. 23. manson je. pain: sex differences and implications for treatment. metabolism. 2010; 59 suppl 1:s16-20. doi: 10.1016/j.metabol.2010.07.013. 24. craft rm, mogil js, aloisi am. sex differences in pain and analgesia: the role of gonadal hormones. eur j pain. 2004; 8:397-411. 25. harrison jl, davis kd. cold-evoked pain varies with skin type and cooling rate: a psychophysical study in humans. pain. 1999; 83:123-35. 26. kennard ma. the responses to painful stimuli of patients with severe chronic painful conditions. j clin invest. 1952; 31:245-52. 27. riley jl 3rd, robinson me, wise ea, et al. sex differences in the perception of noxious experimental stimuli: a metaanalysis. pain. 1998; 74:181-7. 28. otto mw, dougher mj. sex differences and personality factors in responsivity to pain. percept mot skills. 1985; 61:383-90. 29. levine fm, de simone ll. the effects of experimenter gender on pain report in male and female subjects. pain. 1991; 44:69-72. 30. feine js, bushnell mc, miron d, et al. sex differences in the perception of noxious heat stimuli. pain. 1991;44:255-62. 31. bertrand al, garcia jb, viera eb, et al. pupillometry: the influence of gender and anxiety on the pain response. pain physician. 2013; 16:e257-66. skin july 2018 volume 2 issue 4 copyright 2018 the national society for cutaneous medicine 240 brief article primary cutaneous cryptococcosis in an immunocompetent 6-year-old female mitchell hobbs md a , joy king md phd b , rana el feghaly md msci c , robert brodell md d a university of mississippi school of medicine, department of pediatrics b university of mississippi school of medicine, department of pathology c university of missouri-kansas city school of medicine, department of pediatrics d university of mississippi school of medicine, department of dermatology primary cutaneous cryptococcosis (pcc) refers to an infectious process seen in immunocompetent patients wherein cryptococcal organisms directly inoculate the skin by exposure, typically in unclothed areas. unlike cryptococcal infections in the immunocompromised, pcc has not been known to spread systemically and responds well to oral antifungal agents. the literature reports pcc typically affects older males in rural areas with hobbies or work predisposing exposure, making pediatric cases atypical. a 6-year-old female presented to the ed with the complaint of a right eyebrow “abscess” for one month prior to presentation (figure 1). she had been treated at a local hospital two weeks prior at which time incision and drainage was attempted but failed to produce any exudate. following this procedure, she received 5 days of empirical iv ceftriaxone and clindamycin and completed a further 7 days of oral clindamycin and topical mupirocin as an outpatient. these therapies had failed to improve the lesion which had continued to grow as well as “crust over” and bleed at times with associated tenderness. the patient denied pruritis as well as systemic abstract a 6-year-old otherwise healthy female presented to the ed with a right eyebrow lesion for one month. previous i&d attempts and empiric antibiotic treatment had failed to improve the lesion. following dermatology referral, superficial culture resulted with growth of cryptococcus neoformans after which completion of oral fluconazole treatment resolved the lesion. though cryptococcus neoformans infections commonly plague immunocompromised patients, primary cutaneous cryptococcosis in the immunocompetent patient is a rare but documented infection with a paucity of reported pediatric cases, and frontline physicians should be aware of such a diagnosis in the setting of persistent skin lesions without response to more commonly utilized therapies. introduction case report skin july 2018 volume 2 issue 4 copyright 2018 the national society for cutaneous medicine 241 symptoms including fever, chills, weakness, or rashes elsewhere. she had never had this problem before, and medical and family histories were negative for immunodeficiency. she lives in rural mississippi without any known animal or environmental exposures. on exam, a 3 cm crusted plaque with rolled, friable borders was noted of the right eyebrow. shave biopsy was obtained as well as superficial cultures which returned with plentiful yeast forms and growth of cryptococcus neoformans, respectively (figure 2). serum cryptococcal antigen was negative. the lesion resolved with a course of oral fluconazole. figure 1. 3 cm crusted plaque with rolled, friable borders over the right eyebrow. figure 2. gms stain of shave biopsy with yeast forms staining dark. primary cutaneous cryptococcosis (pcc) is defined as direct inoculation and infection of the skin, and it is a rare condition in immunocompetent patients. 1 a recent systematic review revealed 21 published cases in immunocompetent patients from 2004 to 2014 with certain commonalities; those infected tended to be male, older in age with upper limb lesions, inhabitants of rural areas, and engaged in work or hobbies predisposed to hand injury in the presence of soil, wood debris, or birds. 2,3 of these known factors, our patient differed with the exception of rural living area. presentation of the lesion varies significantly and in reported cases has included whitlow, phlegmon, ulceration, nodule, and cellulitis, typically in unclothed areas—most commonly fingers and hands. 3 when genotype and serotype have been identified in isolates, prevalence of c. neoformans and c. gattii have been nearly equal followed by c. laurentii in the minority of cases. treatment has been typically successful with systemic fluconazole, and in recalcitrant cases, itraconazole is useful as a secondline option. 2 as an alternative means of therapy, surgical excision and further monitoring has been reported with resolution in the absence of systemic antifungal therapy. 4 one patient has been reported to exhibit dissemination from primary infection, discussion skin july 2018 volume 2 issue 4 copyright 2018 the national society for cutaneous medicine 242 but this is favored to be a rarity as more cases have been reported to have resolved without intervention, suggesting most patients’ immune systems are capable of overcoming the infection. 2,5 in contrast, secondary cutaneous crytococcosis is known to result from hematogenous dissemination in the setting of a systemically infected immunocompromised host. in the classic and relatively common clinical scenario, exposure in the immunocompromised patient occurs via inhalation of spores ubiquitous in the environment resulting in primary infection of the lungs followed by cns manifestations. the indolent clinical course includes symptoms such as fever, malaise, headache, cough, and dyspnea. a classic cutaneous finding appears as umbilicated papules. 6 in consideration of the evolving knowledge of this clinical entity and the well-known pathologies this organism usually inflicts on the immunocompromised, the significance of our case of pcc in a 6-year-old immunocompetent female is two-fold. first, it broadens known epidemiologic data of a disease with a typical presentation at odds with our patient’s. second, it augments awareness of a rare dermatologic disease in otherwise healthy patients that is refractory to commonly employed therapies and caused by a pathogen most commonly associated with medically complex, immunosuppressed patients. conflict of interest disclosures: none funding: none corresponding author: mitchell hobbs, md university of mississippi school of medicine 2500 n. state street jackson, ms 39216 601-720-4998 (office) mhobbs@umc.edu references: 1. nascimento e, bonifácio da silva me, martinez r, von zeska kress mr. primary cutaneous cryptococcosis in an immunocompetent patient due to cryptococcus gattii molecular type vgi in brazil: a case report and review of literature. mycoses. 2014 jul;57(7):442-7. 2. du l, yang y, gu j, chen j, liao w, zhu y. systemic review of published reports on primary cutaneous cryptococcosis in immunocompetent patients. mycopathologia. 2015 aug;180(1-2):19-25. 3. neuville s, dromer f, morin o, dupont b, ronin o, lortholary o; french cryptococcosis study group. primary cutaneous cryptococcosis: a distinct clinical entity. clin infect dis. 2003 feb 1;36(3):337-47. 4. lenz d, held j, goerke s, wagner d, tintelnot k, henneke p, hufnagel m. primary cutaneous cryptococcosis in an eight-year-old immunocompetent child: how to treat? klin padiatr. 2015 jan;227(1):41-4. 5. spiliopoulou a, anastassiou ed, christofidou m. primary cutaneous cryptococcosis in immunocompetent hosts. mycoses. 2012 mar; 55 (2): e45-7. 6. kliegman, robert m, nina schor, bonita stanton, and joseph w. st geme iii. nelson textbook of pediatrics. philadelphia: elsevier, 2016. skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 603 brief articles ixekizumab overdose: a case report margaret l. snyder, md1, mark g. lebwohl, md1 1department of dermatology, icahn school of medicine at mount sinai, new york, ny biologics, defined as medicinal products derived from living cells, are currently some of the most studied pharmaceutical agents and constitute a large portion of recent therapeutic breakthroughs in clinical trials. relatively novel to the scientific and medical community, insulin was the first biologic agent to be fda-approved in the 1980’s.1 since that time, the development of therapeutic monoclonal antibodies by milstein and kohler has revolutionized modern medicine, with over 100 products currently on the market for the prevention and treatment of infectious, neoplastic, autoimmune, and inflammatory diseases.2,3 despite the remarkable clinical success that monoclonal antibodies have achieved since their development, safety data is still limited due to the relatively short duration of time these products have been available. specifically, there is a considerable paucity of information regarding inadvertent biologic overdose, with most package inserts simply advising clinicians to monitor their patients for symptoms. due to complex dosing schedules as well as increasing use of these agents, it is likely that healthcare providers will encounter cases of patients accidentally self-administering larger than recommended doses. it is thus imperative to have more data on maximum tolerated doses in order for clinicians to educate and care for their patients in the case of accidental biologic abstract biologics, defined as medicinal products derived from living cells, are currently some of the most studied pharmaceutical agents and constitute a large portion of recent therapeutic breakthroughs in clinical trials. relatively novel to the scientific and medical community, insulin was the first biologic agent to be fda-approved in the 1980’s.1 since that time, the development of therapeutic monoclonal antibodies by milstein and kohler has revolutionized modern medicine, with over 100 products currently on the market for the prevention and treatment of infectious, neoplastic, autoimmune, and inflammatory diseases.2,3 despite the remarkable clinical success that monoclonal antibodies have achieved since their development, safety data is still limited due to the relatively short duration of time these products have been available. specifically, there is a considerable paucity of information regarding inadvertent biologic overdose, with most package inserts simply advising clinicians to monitor their patients for symptoms. due to complex dosing schedules as well as increasing use of these agents, it is likely that healthcare providers will encounter cases of patients accidentally selfadministering larger than recommended doses. it is thus imperative to have more data on maximum tolerated doses in order for clinicians to educate and care for their patients in the case of accidental biologic overdose. we therefore present a case of inadvertent administration of a higher than recommended dose of ixekizumab and review the available literature on biologic overdoses. introduction skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 604 overdose. we therefore present a case of inadvertent administration of a higher than recommended dose of ixekizumab and review the available literature on biologic overdoses. a 69-year-old male with chronic plaque psoriasis presented to clinic for follow up after previously failing multiple therapies, including: etanercept, adalimumab, infliximab, ustekinumab, and risankizumab. the patient was initiated on ixekizumab 160 mg subcutaneously (two syringes, loading dose) at week 0, followed by instructions to administer 80 mg subcutaneously (one syringe, maintenance dose) on weeks 2, 4, 6, 8, 10, and 12. during week 7 of therapy, the pharmacy called and informed us that the patient had injected two syringes (total of 160 mg) on weeks 2, 4 and 6. upon further questioning, it became apparent that the patient misunderstood the instructions and had inadvertently administered twice the recommended dose on these weeks. he did not experience any adverse effects, but did notice significant improvement in his psoriatic lesions. the patient was instructed to hold the medication for one month, after which time he initiated the recommended dose of one syringe (80 mg) on weeks 10 and 12. he is now on the recommended medication regimen and continues to do well with no adverse effects. despite biologic agents being one of the fastest growing domains of pharmaceutical research with increasing numbers of new drugs approved for market use every year, there is very little data regarding inadvertent drug overdose. in fact, most information available to clinicians is limited to package inserts or online prescribing information pages, and even these often exclusively include a generic statement such as “in the case of inadvertent overdose, monitor the patient for signs and symptoms of adverse effects”. this paucity of guidance for clinicians limits their ability to adequately counsel and monitor their patients in the event a higher than recommended dose of biologic medication is accidentally administered, either by the patient themselves or by healthcare personnel. we therefore report a case of inadvertent overdose of ixekizumab in order to augment the scientific literature and equip healthcare providers and patients with more pertinent information. by nature of their chemical structure as “large molecules”, biologic agents must be injected intravenously or subcutaneously. due to the pharmacokinetic properties and bioavailability of these agents, it is common for a larger “loading dose” injection to be used to initiate treatment, followed by a lower “maintenance dose” to be administered at specific time intervals, depending on the medication and its indication for use. due to this inconsistency with dosing, it is easy to imagine how patients may become confused while selfadministering at home, even in the most controlled of circumstances, such as during a clinical trial. for example, in the ascertain trial comparing the safety and efficacy of sarilumab and tocilizumab in rheumatoid arthritis, accidental overdose of tocilizumab occurred in 8.8% of patients.4 thankfully, dose-limiting toxicities are often not observed; in fact, a single iv overdose of up to 40 mg/kg of tocilizumab has been reported with no adverse drug reaction.5 furthermore, package inserts/prescribing information pages report administration of higher than currently recommended doses case presentation discussion skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 605 table 1. citation drug overdose biologic target effect tocilizumab package insert tocilizumab, one case of 40 mg/kg single iv infusion il-6 no adverse drug reactions observed tocilizumab package insert tocilizumab, 5 healthy volunteers received 28 mg/kg single dose il-6 all 5 patients developed dose-limiting neutropenia; there were no serious adverse reactions infliximab package insert infliximab, 20 mg/kg single dose tnf no direct toxic effect secukinumab package insert secukinumab, 30 mg/kg single iv infusion il-17a no dose-limiting toxicity taliercio m, alessa d, kessler db secukinumab, 300 mg qd x 5 days il-17a dry, peeling skin; no other adverse effects alemtuzumab package insert alemtuzumab, 2 patients received 60 mg single iv infusion cd52 headache, rash, hypotension or sinus tachycardia belimumab package insert belimumab, 20 mg/kg iv infusion blys (b-cell survival factor) no increase in severity of adverse reactions compared with lower doses certolizumab package insert certolizumab, 800 mg sq and 20 mg/kg iv tnf no evidence of doselimiting toxicity golimumab package insert golimumab, 5 patients received single iv infusion of up to 1000 mg tnf no serious adverse reactions or other significant reactions omalizumab package insert omalizumab, single iv infusion of 4,000 mg ige no evidence of doselimiting toxicities of infliximab and secukinumab during clinical trials with no dose-limiting adverse effects.6,7 an additional case of overdose of secukinumab with no resultant adverse effects has also been reported.8 the lack of dose-limiting toxicities in all of these instances highlights the generally welltolerated nature of monoclonal antibodies as pharmacological agents. it is believed that this tolerance of high doses is due to the high specificity of therapeutic monoclonal antibodies, meaning that even at elevated doses, non-target cytokines or other proteins are not likely to be inhibited.9 at times, higher doses may even have therapeutic benefits. for example, in a historicprospective study of 147 patients treated with omalizumab in france, rates of drug discontinuation due to unsatisfactory therapeutic benefit were lower in those who overdosed on medication.10 in contrast to the relative safety of large doses of the aforementioned therapies, however, there are reports of adverse effects or significant laboratory abnormalities associated with overdose of other biologics. for instance, two patients with multiple sclerosis experienced headache, rash, hypotension, skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 606 and sinus tachycardia after an accidental single infusion of up to 60 mg of alemtuzumab.11 likewise, healthy volunteers who received 28 mg/kg single dose of tocilizumab all developed doselimiting neutropenia.5 contrary to trials for autoimmune and auto-inflammatory disorders, a study of 150 patients with new york heart association class iii or iv heart failure treated with infliximab demonstrated adverse clinical outcome at 10mg/kg but not at 5mg/kg.12 table 1 summarizes the aforementioned reports of administration of higher than standard doses of monoclonal antibodies.5-8, 11, 13-16 the discrepancy in effects of biologic overdose on patient safety emphasizes the importance of gathering more information specific to each agent in the setting of overdose. it appears as though the baseline health of the patient may play a role in their tolerance to higher dosages, as evidenced by the inconsistency of effect of infliximab dosage in healthy patients versus those with heart failure.6,12 however, there are currently too few reports in the literature to discern a pattern or ascertain if certain classes of biologic agents are more likely than others to lead to adverse events in the setting of overdose. therefore, more information specific to each specific agent and biologic class is needed. to our knowledge, we are the first to report a case of inadvertent overdose of ixekizumab. like many reports of higher than recommended dosage of other monoclonal antibodies, our patient did not experience any adverse effects. we present this information in order for clinicians to be prepared to monitor and counsel their patients in the setting of inadvertent overdose, as well as to highlight the need for careful and thorough dosing education when initiating patients on biologic therapies. conflict of interest disclosures: mark lebwohl is an employee of mount sinai and receives research funds from: abbvie, amgen, arcutis, boehringer ingelheim, dermavant, eli lilly, incyte, janssen research & development, llc, leo pharmaceutucals, ortho dermatologics, pfizer, and ucb, inc.and is a consultant for aditum bio, allergan, almirall, arcutis, inc., avotres therapeutics, birchbiomed inc., bmd skincare, boehringeringelheim, bristol-myers squibb, cara therapeutics, castle biosciences, corrona, dermavant sciences, evelo, facilitate international dermatologic education, foundation for research and education in dermatology, inozyme pharma, kyowa kirin, leo pharma, meiji seika pharma, menlo, mitsubishi, neuroderm, pfizer, promius/dr. reddy’s laboratories, serono, theravance, and verrica. margaret snyder is an employee of the icahn school of medicine at mount sinai dermatology department and works as a sub-investigator on clinical trials sponsored by abbvie, arcutis, dermira, eli lilly, incyte, pfizer, and ucb, inc. funding: none corresponding author: margaret l. snyder, md icahn school of medicine at mount sinai department of dermatology 5 east 98th street new york, ny 10029 phone: 803-292-0110 email: margaret.snyder@mssm.edu references: 1. refs vecchio i, tornali c, bragazzi nl, martini m. the discovery of insulin: an important milestone in the history of medicine. frontiers in endocrinology 2018;9:613. 2. kohler g, milstein c. continuous cultures of fused cells secreting antibody of predefined specificity. nature 1975;256:495–7. 3. kohler g, milstein c. derivation of specific antibody-producing tissue culture and tumor lines by cell fusion. eur j immunol 1976;6:511–9. 4. emery p, rondon j, parrino j, lin y, pena-rossi c, van hoogstraten h, et al. safety and tolerability of subcutaneous sarilumab and intravenous tocilizumab in patients with conclusion skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 607 rheumatoid arthritis. rheumatology (oxford, england) 2019; 58(5):849-858. 5. tocilizumab [package insert]. south san francisco, ca: genentech, inc.; 2010. 6. infliximab [package insert]. thousand oaks, ca: amgen, inc.; 2019. 7. secukinumab [package insert]. east hanover, nj: novartis pharmaceuticals corporation; 2015. 8. taliercio m, alessa d, kessler db. inadvertent overdose of secukinumab, consequences, and cautions. journal of psoriasis and psoriatic arthritis 2016; 1(4):147-9. 9. navarini aa, muster ma, kolios ag, frische p, glatz m, french le, et al. weight-based adaptation of tnf-antagonist induction versus maintenance dose. case reports in dermatology 2011; 3(2):124-9. 10. molimard m, de blay f, didier a, le gros v. effectiveness of omalizumab (xolair) in the first patients treated in real-life practice in france. respiratory medicine 2008; 102(1):71-6. 11. alemtuzumab [package insert]. cambridge, ma: genzyme corporation; 2001. 12. chung es, packer m, hung lo k, fasanmade aa, willerson jt. randomized, double-blind, placebo-controlled, pilot trial of infliximab, a chimeric monoclonal antibody to tumor necrosis factor-alpha, in patients with moderate-to-severe heart failure: results of the anti-tnf therapy against congestive heart failure (attach) trial. circulation 2003;107(25):3133-40. 13. belimumab [package insert]. rockville, ma: human genome sciences, inc.; 2018. 14. certolizumab [package insert]. smyrna, ga: ucb, inc.; 2008. 15. golimumab [package insert]. horsham, pa: janssen biotech, inc.; 2009. 16. omalizumab [package insert]. south san francisco, ca: genentech, inc.; 2003. long-term safety of sonidegib in basal cell carcinoma: 30-month results from the bolt trial ragini kudchadkar, md1; anne lynn s. chang, md2 1associate professor, hematology and medical oncology, emory university school of medicine, atlanta, ga, usa; 2associate professor, dermatology, stanford university school of medicine, redwood city, ca, usa. presented at 2018 winter clinical dermatology conference – hawaii, lahaina, hawaii, usa background basal cell carcinoma (bcc) is the most common form of skin cancer1 – more than 4 million cases are diagnosed in the united states (us) each year2 the incidence and prevalence of bcc is expected to increase as the population ages3 ~95% of patients with bcc have mutations in the hedgehog (hh) signaling pathway components patched-1 (ptch1; >85%) or smoothened (smo; ~10%)4 sonidegib blocks the hh signaling pathway by selective inhibition of the smo protein5 (figure 1) sonidegib was approved based on results of the pivotal phase bolt (basal cell carcinoma outcomes with lde225 [sonidegib] treatment) trial (nct01327053)6 (figure 2) sonidegib is approved in the us, the european union, switzerland, and australia for the treatment of patients with locally advanced basal cell carcinoma (labcc)6 in switzerland and australia, sonidegib is also approved for the treatment of metastatic bcc (mbcc)6 results patient demographics and disposition two-hundred-thirty patients with labcc (n=194) or mbcc (n=36) were enrolled between july 20, 2011, and january 10, 20139 (table 1) patients were randomized to sonidegib 200 mg (labcc, n=66; mbcc, n=13) or 800 mg (labcc, n=128; mbcc, n=23)9 baseline demographics were well balanced between arms separated adverse events profile for labcc and mbcc the most common ae for sonidegib at either dosage in labcc was muscle spasms9 (figure 4) the most common ae for 200 mg qd in mbcc was diarrhea; for 800 mg qd, it was muscle spasm9 (figure 5) a total of 8 deaths were reported in bolt, none of which were deemed related to treatment9 – 4 deaths occurred in patients with labcc; 1 death occurred in the 200-mg arm, and 3 deaths occurred in the 800-mg arm9 – 4 deaths occurred in patients with mbcc; all occurred in the 800-mg arm9 adverse events profile for labcc and mbcc combined at 30 months, the most common (>20% of patients) aes associated with a once-daily 200-mg dose of sonidegib were muscle spasms (54%; 51% grades 1-2), alopecia (50%; all grades 1-2), dysgeusia (44%; all grades 1-2), and nausea (39%; 38% grades 1-2) few grade 3-4 aes were reported9 increased creatine kinase (ck) and rhabdomyolysis were the most commonly reported serious aes among all patients – because there was no renal impairment, none of the cases of rhabdomyolysis were confirmed by an independent review and adjudication committee of experts on muscle toxicity – rhabdomyolysis was defined as ck concentrations >10-fold higher than baseline + 1.5-fold increase in creatinine concentration in serum from baseline9 at the time of the 30-month analysis, >90% of patients in each arm had discontinued treatment9 (table 2) aes leading to treatment discontinuation in the 200-mg arm occurred in 29% of patients compared to 38% in the 800-mg arm9 more patients receiving sonidegib 200 mg qd were able to stay on treatment until disease progression compared fo in the 800-mg qd group9 conclusions at the bolt 30-month analysis, sonidegib treatment demonstrated long-term safety and tolerability, with no new safety concerns emerging in patients with either labcc or those with mbcc sonidegib 200 mg demonstrated a better benefit– risk profile compared with sonidegib 800 mg qd these data support the use of sonidegib 200 mg for the treatment of patients with labcc or mbcc according to local treatment guidelines references 1. mohan sv, chang als. advanced basal cell carcinoma: epidemiology and therapeutic innovations. curr dermatol rep. 2014;3(1):40-45. 2. rogers hw, weinstock ma, feldman sr, coldiron bm. incidence estimate of nonmelanoma skin cancer (keratinocyte carcinomas) in the us population, 2012. jama dermatol 2015;151(10):1081-1086. 3. kish t, corry l. sonidegib (odomzo) for the systemic treatment of adults with recurrent, locally advanced basal cell skin cancer. p t. 2016;41(5):322-325. 4. epstein eh. basal cell carcinomas: attack of the hedgehog. nat rev cancer. 2008;8(10):743-754. 5. chen l, aria ab, silapunt s, lee hh, migden mr. treatment of advanced basal cell carcinoma with sonidegib: perspective from the 30-month update of the bolt trial. future oncol. 2017 nov 9. doi: 10.2217/fon-2017-0457. [epub ahead of print] 6. burness cb. sonidegib: first global approval. drugs. 2015;75(13):1559-1566. 7. migden mr, guminski a, gutzmer r. treatment with two different doses of sonidegib in patients with locally advanced or metastatic basal cell carcinoma (bolt): a multicentre, randomised, double-blind phase 2 trial. lancet oncol. 2015;16(6):716-728. 8. us department of health and human services. common terminology criteria for adverse events (ctcae) version 4.0. washington, dc: national institutes of health; may 28, 2009 (v4.03: june 14, 2010). nih publication no. 09-5410. available at: https://evs.nci.nih.gov/ftp1/ctcae/ctcae_4.03_2010-06-14_ quickreference_8.5x11.pdf. 9. lear jt, migden mr, lewis kd, et al. long-term efficacy and safety of sonidegib in patients with locally advanced and metastatic basal cell carcinoma: 30-month analysis of the randomized phase 2 bolt study. j eur acad dermatol venereol. 2017 aug 28. doi: 10.1111/ jdv.14542. [epub ahead of print] acknowledgments the funding for this presentation was contributed by sun pharmaceutical industries ltd. writing assistance was provided by beverly e. barton, phd, and nicola donelan, phd, of scioscientific, llc. disclosures dr. kudchadkar has participated on advisory boards, received research funding from merck, consulting fees from bristol-myers squibb, and received honoraria from genentech, inc., novartis pharmaceuticals corporation, sun pharmaceutical industries ltd., and eli lilly & company. dr. chang has received honoraria for participation on an advisory board for genentech, inc., and has served as an investigator and received grants from genentech, inc. and novartis pharmaceuticals corporation. gli1, human glioma-associated oncogene homolog 1; hh, hedgehog; ptch1, patched-1; smo, smoothened. (adapted from 5) figure 1. sonidegib mechanism of action • binding of hh signaling ligand to ptch1 leads to release of smo inhibition • smo activation causes gli1 to cross the nuclear membrane, where it activates genes involved in tumorigenesis • sonidegib inhibits hh pathway signaling via smo antagonism objectives hedgehog pathway inhibitors are a relatively recent class of drugs their long-term safety profile is not yet well characterized safety was one of the key secondary endpoints from the bolt clinical trial adverse events (aes) monitored at 30 months in labcc and mbcc are reported here methods bolt study design bolt was a randomized, double-blind phase 2 clinical trial conducted in 58 centers across 12 countries7 (figure 2) adults enrolled had either histologically confirmed labcc (not amenable to curative surgery or radiation) or had mbcc (where all other treatment options had been exhausted) patients received either 200 mg or 800 mg of sonidegib once daily (figure 2) patient populationa: • labcc (aggressive and nonaggressive subtypes) • mbcc 21 days treatment until one of the following: • disease progression • unacceptable toxicity • death • discontinuation for any other reason patient populationa: • labcc (aggressive and nonaggressive subtypes) • mbcc screening/ baseline treatment follow-up sur vival patient population: • labcc (aggressive and nonaggressive subtypes) • mbcc • tumor assessments until disease progression • information collected on other antineoplastic therapy received • safety follow-up 30 days after last dose of study treatment survival followup every 12 weeks until one of the following: • death • loss to follow-up • withdrawal of consent • final analysis stratification and randomization (1:2) sonidegib 800 mg qd ≤ sonidegib 200 mg qd figure 2. bolt study design labcc, locally advanced basal cell carcinoma; mbcc, metastatic basal cell carcinoma; qd, once daily. safety/monitoring aes monitoring of aes was done according to the national cancer institute common terminology criteria for adverse events version 4.038 aes were assessed by central and investigator review from the first dose until 30 days after the last dose in patients who received at least one dose of sonidegib muscle-related events were also assessed by an independent safety review and adjudication committee composed of three external experts table 1. patient demographics and disease history sonidegib dose (qd) 200 mg (n=79) 800 mg (n=151) median age (range), years 67 (25-92) 65 (24-93) male, % 61 64 eastern cooperative oncology group performance status, % 0 63 63 1 24 29 2 10 7 unknown 3 1 aggressive histological/cytological subtype for patients with labcc based on randomization/stratification, % n=66 n=128 aggressive subtypea 56 59 nonaggressive subtypeb 44 41 metastasis, % 18 15 metastatic sites, % of total patients with metastasis lung 71 52 lymph nodesc 7 30 bone 14 22 otherd 21 30 prior antineoplastic therapy, % surgery 75 83 radiotherapy 24 32 aincludes micronodular, infiltrative, multifocal, basosquamous, and sclerosing histological subtypes. bincludes nodular and superficial histological subtypes. cincludes axillary, parotid, submandibular, supraclavicular, and other. dincludes trunk, brain, head, liver, neck, and upper extremities. labcc indicates locally advanced basal cell carcinoma; qd, once daily. table 2. patient disposition sonidegib dose (qd) 200 mg (n=79) 800 mg (n=150) analysis primarya 30-monthb primarya 30-monthb median duration of exposure (range), months 8.9 (1.3-21.4) 11.0 (1.3-41.3) 6.5 (0.3-19.1) 6.6 (0.3-43.5) treatment ongoing, % 49 8 31 6 treatment discontinued, % 51 92 69 94 primary reasons for discontinuation, % adverse event progressive diseasec patient decisiond physician decisiond loss to follow-up death nonadherence protocol deviation 20 19 6 4 1 0 0 0 29 37 10 13 3 1 0 0 32 4 19 7 3 3 2 1 38 15 22 9 3 3 3 1 adata cutoff: june 28, 2013; median follow-up was 13.9 months in both treatment arms combined. bdata cutoff: july 10, 2015; median follow-up was 38.2 months in both treatment arms combined. cimproved tolerability of the 200-mg dose allowed more patients to stay on treatment until disease progression than with the 800-mg dose. ddiscontinuations due to patient or physician decision were primarily attributed to adverse events. qd, once daily. figure 4. adverse events (aes) reported in ≥20% of labcc patients treated with sonidegib figure 3. adverse events (aes) reported in ≥20% of all (labcc and mbcc) patients treated with sonidegib figure 5. adverse events (aes) reported in ≥20% of mbcc patients treated with sonidegib 0 10 20 30 40 50 60 70 grade 1 grade 2 grade 3 grade 4 muscle spasms alopecia dysgeusia nausea weight decrease fatigue diarrhea appetite decrease 11vomiting myalgiaad ve rs e ev en ts in ≥ 20 % o f p at ie nt s w ith la bc c in 8 00 -m g ar m patients, % 0 10 20 30 40 50 60 70 grade 1 grade 2 grade 3 grade 4 45 8 3muscle spasms 56% 38 14alopecia 52% 35 12dysgeusia 47% 24 12 2nausea 38% 18 8 6weight decrease 32% 15 9 3 2creatine kinase increase creatine kinase increase 29% 17 11 2fatigue 29% 23 3 2diarrhea 27% all grades , % ad ve rs e ev en ts in ≥ 20 % o f p at ie nt s w ith la bc c in 2 00 -m g ar m patients, % 800 mg 200 mg 36 28 5 69% 35 26 61% 42 17 59% 31 12 2 46% 13 21 6 40% 13 11 10 5 39% 24 7 2 32% 17 7 24% 24 9 3 36% 20 5 2 27% 21 4 2 27% all grades , % 0 10 20 30 40 50 60 70 grade 1 grade 2 grade 3 grade 4 muscle spasms alopecia dysgeusia nausea weight decrease fatigue diarrhea appetite decrease 11vomiting myalgia patients, % 0 10 20 30 40 50 60 70 grade 1 grade 2 grade 3 grade 4 44 8 3muscle spasms 54% 37 13alopecia 49% 32 13dysgeusia 44% 27 11 1nausea 39% 16 9 5weight decrease 30% 15 9 4 3creatine kinase increase creatine kinase increase 30% 18 11 1fatigue 30% 27 4 1diarrhea 32% 10 11 1appetite decrease 23% all grades , % all grades , % ad ve rs e ev en ts in ≥ 20 % o f a ll pa tie nt s (la bc c + m bc c) ad ve rs e ev en ts in ≥ 20 % o f a ll pa tie nt s (la bc c + m bc c) patients, % 800 mg 200 mg 37 27 5 69% 35 23 58% 41 19 60% 31 13 3 47% 12 25 6 43% 12 12 9 4 37% 26 9 2 37% 15 9 24% 21 11 4 35% 20 6 2 28% 24 3 1 29% 0 10 20 30 40 50 60 70 grade 1 grade 2 grade 3 grade 4 muscle spasms alopecia dysgeusia nausea weight decrease fatigue diarrhea appetite decrease 11vomiting myalgiaad ve rs e ev en ts in ≥ 20 % o f p at ie nt s w ith la bc c in 8 00 -m g ar m patients, % 0 10 20 30 40 50 60 70 grade 1 grade 2 grade 3 grade 4 45 8 3muscle spasms 56% 38 14alopecia 52% 35 12dysgeusia 47% 24 12 2nausea 38% 18 8 6weight decrease 32% 15 9 3 2creatine kinase increase creatine kinase increase 29% 17 11 2fatigue 29% 23 3 2diarrhea 27% all grades , % ad ve rs e ev en ts in ≥ 20 % o f p at ie nt s w ith la bc c in 2 00 -m g ar m patients, % 800 mg 200 mg 36 28 5 69% 35 26 61% 42 17 59% 31 12 2 46% 13 21 6 40% 13 11 10 5 39% 24 7 2 32% 17 7 24% 24 9 3 36% 20 5 2 27% 21 4 2 27% all grades , % 0 10 20 30 40 50 60 70 grade 1 grade 2 grade 3 grade 4 muscle spasms alopecia dysgeusia nausea weight decrease fatigue diarrhea appetite decrease 11vomiting myalgia patients, % 0 10 20 30 40 50 60 70 grade 1 grade 2 grade 3 grade 4 44 8 3muscle spasms 54% 37 13alopecia 49% 32 13dysgeusia 44% 27 11 1nausea 39% 16 9 5weight decrease 30% 15 9 4 3creatine kinase increase creatine kinase increase 30% 18 11 1fatigue 30% 27 4 1diarrhea 32% 10 11 1appetite decrease 23% all grades , % all grades , % ad ve rs e ev en ts in ≥ 20 % o f a ll pa tie nt s (la bc c + m bc c) ad ve rs e ev en ts in ≥ 20 % o f a ll pa tie nt s (la bc c + m bc c) patients, % 800 mg 200 mg 37 27 5 69% 35 23 58% 41 19 60% 31 13 3 47% 12 25 6 43% 12 12 9 4 37% 26 9 2 37% 15 9 24% 21 11 4 35% 20 6 2 28% 24 3 1 29% ad ve rs e ev en ts in ≥ 20 % o f p at ie nt s w ith m bc c in 8 00 -m g ar m 0 10 20 30 40 50 60 70 grade 1 grade 2 grade 3 grade 4 43 8 8 8 46 48 8 8 8 muscle spasms 46%38 39 39 8 46%38 54% alopecia dysgeusia 46% nausea 38% weight decrease 38% creatine kinase increase 38%15 15 15 15 fatigue 31% 23 23 23 15 diarrhea 23%8 158 15 8 appetite decrease 23%myalgia arthralgia 23% ad ve rs e ev en ts in ≥ 20 % o f p at ie nt s w ith m bc c in 2 00 -m g ar m patients, % 200 mg 35 35 30 31 17 17 17 9 9 9 0 10 20 30 40 50 60 700 80 grade 1 grade 2 grade 3 grade 4 4 4 179 4 17 4 4 4 muscle spasms 74% 57% 26% alopecia dysgeusia 30% nausea 61% weight decrease 43% creatine kinase increase 30% fatigue 65% 22 22 22 diarrhea 61% 13 appetite decrease 35% vomiting 39% myalgia arthralgia 22% patients, % 800 mg 30 9 9 all grades , % all grades , % ad ve rs e ev en ts in ≥ 20 % o f p at ie nt s w ith m bc c in 8 00 -m g ar m 0 10 20 30 40 50 60 70 grade 1 grade 2 grade 3 grade 4 43 8 8 8 46 48 8 8 8 muscle spasms 46%38 39 39 8 46%38 54% alopecia dysgeusia 46% nausea 38% weight decrease 38% creatine kinase increase 38%15 15 15 15 fatigue 31% 23 23 23 15 diarrhea 23%8 158 15 8 appetite decrease 23%myalgia arthralgia 23% ad ve rs e ev en ts in ≥ 20 % o f p at ie nt s w ith m bc c in 2 00 -m g ar m patients, % 200 mg 35 35 30 31 17 17 17 9 9 9 0 10 20 30 40 50 60 700 80 grade 1 grade 2 grade 3 grade 4 4 4 179 4 17 4 4 4 muscle spasms 74% 57% 26% alopecia dysgeusia 30% nausea 61% weight decrease 43% creatine kinase increase 30% fatigue 65% 22 22 22 diarrhea 61% 13 appetite decrease 35% vomiting 39% myalgia arthralgia 22% patients, % 800 mg 30 9 9 all grades , % all grades , % labcc, locally advanced basal cell carcinoma, mbcc metastatic bcc. labcc, locally advanced basal cell carcinoma. mbcc, metastatic basal cell carcinoma. introduction • the physician global assessment and body surface area (pgaxbsa) composite tool is simple to use for the assessment of both severity and extent of psoriasis and correlates with the product of the more complex psoriasis area and severity index (pasi) tool.1-3 • in prior retrospective analyses of the effi cacy and safety trial evaluating the effects of apremilast in psoriasis (esteem; nct01194219 and nct01232283) phase iii clinical trial data, the pgaxbsa and pasi demonstrated ≥79% response concordance and achieved cohen’s effect sizes >0.8, indicating sensitivity to therapeutic change.4 • pgaxbsa has also demonstrated sensitivity to small changes from baseline in body surface area (bsa), unlike the non-linear pasi tool,1,5 and thus may be a more sensitive tool for assessing response in patients with moderate psoriasis. • the phase iv randomized, placebo (pbo)-controlled, double-blind study evaluating apremilast in a phase iv trial of effi cacy and safety in patients with moderate plaque psoriasis (unveil) (nct02425826) is the fi rst prospective trial to evaluate the effi cacy and safety of oral apremilast 30 mg twice daily (apr) in patients with moderate plaque psoriasis (psoriasisinvolved bsa of 5% to 10%) who are naive to systemic and biologic therapy. • this analysis compared correlations between pgaxbsa and pasi in 2 distinct populations of patients with moderate plaque psoriasis from esteem 1 and unveil. methods • data were collected from patients with moderate plaque psoriasis who were randomly assigned to receive apr at baseline in the esteem 1 trial (n=562) and the unveil trial (n=148). • esteem 1 was a phase iii, multicenter, randomized, double-blind, pbocontrolled study (figure 1). – eligible patients were randomized (2:1) to receive apr or pbo, titrated over the fi rst week of treatment, through week 16. – at week 16, pbo patients were switched to apr, with titration. dosing was maintained from weeks 16 to 32 (maintenance phase). – the maintenance phase was followed by a blinded, randomized treatment withdrawal phase through week 52. • unveil was a phase iv randomized, double-blind, pbo-controlled study (figure 2). – eligible patients were randomized (2:1) to receive apr or pbo, titrated over the fi rst week of treatment. – at week 16, all pbo patients were switched to open-label apr (with titration) through week 52. methods (cont’d) figure 1. esteem 1 study design week 0 week 16 week 32 week 52 apremilast 30 mg bid* placebo ≥ pasi-75 < pasi-75 apremilast 30 mg bid placebo apremilast 30 mg bid* < pasi-75 ≥ pasi-75 at time of loss of effect§ apremilast 30 mg bid apremilast 30 mg bid ± topicals, uvb‡ ra n d o m iz e (1 :2 ) screen long-term extension for up to 5 years apremilast 30 mg bid ± topicals, uvb‡ *doses of apremilast were titrated during the fi rst week of administration and at week 16 when placebo patients were switched to apremilast. §patients re-started apremilast at the time of loss of effect obtained at week 32 vs. baseline (loss of pasi-75) but no later than week 52. ‡patients initially on placebo or randomized to apremilast 30 mg bid who did not attain pasi-75 were able to add topicals and/or uvb light therapy at week 32 at the discretion of the investigator. bid=twice daily; pasi=psoriasis area and severity index; pasi-75=a ≥75% reduction from baseline in pasi score; uvb=ultraviolet b. figure 2. unveil study design ra n d o m iz e 1: 2§screen* placebo (n=73) placebo-controlled phase primary end point: mean percentage change in pgaxbsa at week 16 apremilast 30 mg bid (n=148) open-label treatment phase safety observation apremilast 30 mg bid‡ (n=64) –5 weeks week 16 week 52 week 0 week 56 *screening up to 35 days before randomization. §all doses were titrated over the fi rst week of treatment. ‡at week 16, all placebo patients were switched to open-label apremilast 30 mg bid (with dose titration) through week 52. bid=twice daily; pgaxbsa=product of the static physician’s global assessment and body surface area involvement. • in these 2 studies, psoriasis severity was defi ned as follows: – esteem 1: pasi ≥12, bsa ≥10%, static physician global assessment (spga) ≥3. – unveil: bsa=5% to 10%, spga=3. • agreement between pgaxbsa and pasi at baseline and week 16 was evaluated using spearman correlation (r ) and intra-class correlation coeffi cients (icc). • effect size (mean change from baseline/standard deviation of baseline) was calculated for both pgaxbsa and pasi in the apr treatment group in each trial. results • patients in unveil who received apr had a signifi cantly greater improvement (reduction) in mean percentage change from baseline in pgaxbsa vs. the pbo group at week 16 (p<0.0001) (figure 3). • in addition, 35.4% of apr patients in unveil achieved a ≥75% reduction from baseline in pgaxbsa score (pgaxbsa-75) vs. 12.3% of pbo patients (p<0.0001) (figure 3). figure 3. mean percentage change in pgaxbsa at week 16 in unveil –10.2 –48.1 –80 –60 –40 –20 0 m ea n pe rc en ta ge c ha ng e fr om b as el in e in p ga xb sa pbo n=73 apr n=147 * mean percentage change in pgaxbsa (locf) 12.3 35.4 0 10 20 30 40 50 pe rc en ta ge o f p at ie nt s ac hi ev in g pg ax bs a75 r es po ns e pbo n=73 apr n=147 pgaxbsa-75 response (locf) * *p<0.0001 vs. pbo. locf=last observation carried forward. error bars indicate 2-sided 95% confi dence intervals (cis). • mean percentage changes from baseline in pgaxbsa and pasi scores over the course of the 16-week pbo-controlled period are shown in figure 4; improvement from baseline was greater with pgaxbsa vs. pasi at each time point. figure 4. mean percentage change in pgaxbsa and pasi scores in unveil m ea n pe rc en ta ge c ha ng e fr om b as el in e –80 –60 –40 –20 0 0 4 8 12 16 pbo pasi pbo pgaxbsa apr pasi apr pgaxbsa study week error bars indicate 2-sided 95% cis. results (cont’d) • correlation between pasi and pgaxbsa at baseline was lower in unveil than it was in esteem 1 (table 1). table 1. spearman correlations, icc, and effect sizes: pasi and pgaxbsa at baseline pasi mean (sd) pgaxbsa mean (sd) spearman correlation: pasi vs. pgaxbsa icc (95% ci): standardized pasi vs. pgaxbsa effect size baseline pasi pgaxbsa esteem 1 n=562 18.7 (7.2) 81.8 (54.9) 0.757* 0.89 (0.87, 0.90) na na unveil n=147 8.2 (4.0) 21.8 (5.3) 0.395* 0.42 (0.30,0.56) na na *p<0.0001. effect size=(mean change at time point)/sd baseline ; n=patients with value at the time point indicated; na=not applicable; standardized=(score-mean)/sd. • at week 16, the correlation between pasi and pgaxbsa was lower in unveil as compared with esteem 1 (table 2). • the effect size was larger for pgaxbsa than for pasi in unveil, whereas in esteem 1 the effect size was larger for pasi than for pgaxbsa (table 2). table 2. spearman correlations, icc, and effect sizes: pasi and pgaxbsa at week 16 pasi mean (sd) pgaxbsa mean (sd) spearman correlation: pasi vs. pgaxbsa icc (95% ci): standardized pasi vs. pgaxbsa effect size change from baseline at week 16 pasi pgaxbsa esteem 1 week 16 n=499§ −10.2 (7.3) −46.5 (45.8) 0.807* 0.83 (0.81, 0.86) −1.41 −0.85 unveil week 16 n=120§ −3.9 (3.8) −12.3 (9.4) 0.685* 0.67 (0.57, 0.76) −0.97 −2.51 *p<0.0001. §n=501 for mean change from baseline in pasi score; n=117 for mean change from baseline in pgaxbsa. effect size=(mean change at time point)/sd baseline ; n=patients with value at the time point indicated; na=not applicable; standardized=(score-mean)/sd. conclusions • correlation between pasi and pgaxbsa at baseline and week 16 was lower in unveil (baseline r=0.395, week 16 r=0.685) than it was in esteem 1 (baseline r=0.757, week 16 r=0.807). • the larger effect size for pgaxbsa compared with pasi in unveil suggests that pasi may be less sensitive to change in patients with more moderate disease. • further study is warranted to demonstrate the robustness of this effi cacy measurement. • pgaxbsa is a simple alternative to pasi, and may be more sensitive for assessing the response to treatment in patients with moderate (bsa=5% to 10%) plaque psoriasis. references 1. walsh ja, et al. j am acad dermatol. 2013;69:931-937. 2. chiesa fuxench zc, et al. j am acad dermatol. 2015;73:868-870. 3. spuls pi, et al. j invest dermatol. 2010;130:933-943. 4. duffi n kc, et al. j drugs dermatol. 2017;16:801-808. 5. gottlieb ab, et al. eadv 2016 [poster p2083]. acknowledgments the authors acknowledge fi nancial support for this study from celgene corporation. the authors received editorial support in the preparation of this report from amy shaberman, phd, of peloton advantage, llc, parsippany, nj, usa, funded by celgene corporation, summit, nj, usa. the authors, however, directed and are fully responsible for all content and editorial decisions for this poster. correspondence kristina callis duffi n – kristina.duffi n@hsc.utah.edu disclosures kcd: abbvie, amgen, boehringer ingelheim, bristol-myers squibb, celgene corporation, centocor/janssen, eli lilly, novartis, pfi zer, regeneron, stiefel, and xenoport – consultant, steering committee member, advisory board member, has received grants, and/or has received honoraria. jmj: abbvie, amgen, celgene, dermira, galderma, genentech, janssen, lilly, medimetriks, merck, novartis, pfi zer, promius, and topmd – research, honoraria, consulting and/or other support. jg & el: celgene corporation – employment. jb: abbvie, amgen, boehringer ingelheim, janssen, leo pharma, eli lilly, novartis, pfi zer, and valeant – speaker board member, consultant, and/or research support. presented at: the 2017 fall clinical dermatology conference; october 12–15, 2017; las vegas, nv. evaluation of the pgaxbsa composite tool in patients with moderate vs. moderate to severe plaque psoriasis kristina callis duffi n, md1; j. mark jackson, md2; joana goncalves, md3; eugenia levi, pharmd3; jerry bagel, md4 1university of utah, salt lake city, ut; 2university of louisville, forefront dermatology, louisville, ky; 3celgene corporation, summit, nj; 4psoriasis treatment center of central new jersey, east windsor, nj fc17postercelgeneduffinevaluationpgaxbsa.pdf skin november 2017 volume #1 issue #3 copyright 2017 the national society for cutaneous medicine 169 brief articles atypical fibroxanthoma of the external ear: case report and review of the literature timothy nyckowski bs a , roger ceilley md a,b , andrew bean md a a dermatology p.c., west des moines, ia b university of iowa carver college of medicine, department of dermatology, iowa city, ia atypical fibroxanthoma (afx) is a tumor first reported in 1961 to describe a dermal tumor of atypical spindle cells. 1-4 a retrospective study on 42,279 skin cancers treated using mohs micrographic surgery revealed that .24% of these skin cancers were atypical fibroxanthomas, demonstrating the rarity of this neoplasm. 5 this tumor classically affects elderly caucasian males and most commonly appears as an ulcerated papule or nodule less than 2.0 cm, though variations occur. 2,6 immunohistochemical stains are required for accurate diagnosis, as afx is a diagnosis of exclusion when ruling out more aggressive lesions. the standard of care for afx of the head and neck is currently considered to be mohs micrographic surgery with follow up at 6 month intervals. 2 this case represents the most rapid growing atypical fibroxanthoma of the external ear documented in the existing literature, growing to 3.0 x 2.0 cm in 4-5 weeks. one case report of a 1.0 x 0.8 cm afx that was excised after 2 weeks of growth, and this was the only afx reported in the literature that could have reached similar size in 4-5 weeks. 7 abstract atypical fibroxanthoma (afx) is a rare, dermalbased mesenchymal neoplasm. clinically, these tumors are characterized by rapid, exophytic growth and epidermal ulceration. despite striking clinical features and growth pattern, it is considered to be a tumor of lowto intermediatemalignant potential. we report a case of an 89 year old caucasian male that had a 1 month history of a rapidly enlarging, pedunculated neoplasm on the scapha of his right ear. histologic and immunohistochemical analysis of the lesion were consistent with atypical fibroxanthoma. after a biopsy, the patient underwent a complete resection with mohs micrographic surgery and remains asymptomatic 6 months later. this 3.0 x 2.0 cm lesion emerged over a 4-5 week period, representing the most rapid growing afx of the external ear reported in the literature. introduction skin november 2017 volume #1 issue #3 copyright 2017 the national society for cutaneous medicine 170 an 88 year old caucasian male presented to our outpatient dermatology clinic with a 4-5 week history of a rapidly enlarging, slightly pedunculated mass on the right ear scapha (figure 1). the lesion was asymptomatic and the patient denied local trauma or previous history of such a lesion. the lesion measured 3.0 x2.0 cm and was non-tender, pink, and friable. no regional lymphadenopathy was appreciated. after locally anesthetizing the site, the lesion was excised down to the perichondrium with half of the lesion sent to histology for permanent sections and the other half sectioned and analyzed with frozen section histology in our laboratory. frozen sections obtained in our lab demonstrated a poorly differentiated spindle cell tumor with a large number of mitotic figures (figure 2). the initial differential diagnosis included atypical fibroxanthoma, atypical sarcoma, and figure 1: atypical fibroxanthoam of the right ear spindle cell variant melanoma. positive margins were identified on the base of the lesion prompting mohs surgical removal of the remaining lesion. a significant post-op defect remained after tumor removal, thus porcine xenograft was placed on the surgical site to facilitate the wound to heal by second intention (figure 3). permanent section histology with immunohistochemical staining was faintly focally positive for smooth muscle actin and negative for: h-caldesmon, s-100, sox 10, pan melanocytic cocktail (hmb-45, anti-mart 1 and anti-tyrosinase), ae1/ae3, p63, desmin, erg, p63, cd31, and cd34, confirming the diagnosis of atypical fibroxanthoma. the patient had excellent healing results 3 weeks post-op and continues to be asymptomatic 6 months after removal. figure 2: h&e staining revealing dermal proliferation of atypical spindle cells case report skin november 2017 volume #1 issue #3 copyright 2017 the national society for cutaneous medicine 171 figure 3: reconstruction with porcine xenograft atypical fibroxanthoma (afx) is a tumor that is classically found in elderly caucasian male patients, with most neoplasms occurring on chronically sun-damaged skin. 1-3,9 there are 2 distinct anatomic locations and demographic populations in which these tumors occur. 8 78% of afx occurs in the sun-exposed head and neck, with a median age of 69 among patients affected. 8 the remaining 22% of cases of afx are present in the trunk and limbs, with a median age of 39. 8 afx is at least twice as common in men than women. 2 uv-induced dna damage affecting p53 proteins are central to the pathogenesis of afx. 1,2,10,11 these tumors have an accumulation of inactive p53 proteins on histology and are strongly correlated with sun-damaged skin. 1,2 other risk factors for the development of afx include x-ray exposure, xeroderma pigmentosa, and chronic immunosuppression (hiv, organ transplant). 2,10,11 the cell type that gives rise to afx is under debate, with current sources suggesting an undifferentiated mesenchymal cell with features of fibroblastic, myofibroblastic, or histiocytic origin. 2,3,7 the tumor may appear as a pink to red papule or nodule with superficial ulceration and bleeding. 10 most afx are less than 2.0 cm in diameter, with a 4 month median interval from onset to presentation. 2,9-11 the differential diagnosis includes dermatofibrosarcoma protuberans, malignant fibrous histiocytoma, spindle cell squamous carcinoma, angiosarcoma, kaposi sarcoma, pyogenic granuloma, leiomyosarcoma, and spindle cell variant malignant melanoma. 1,9,10 histologic exam is required for diagnosis. h&e staining shows a well-defined dermal neoplasm with a proliferation of atypical spindle cells haphazardly arranged. 12 though this tumor has a low risk of metastasis, histologic features associated with more aggressive cases of afx behavior include vascular invasion, necrosis, and invasion into the subcutaneous fat. 2 a panel of immunohistochemical stains is usually required to rule out other potential neoplasms. no specific immunohistochemical markers identify afx, but vimentin, cd10, cd68, and p53 are all likely to be positive in cases of afx. 1-3,6,12 it is advisable to order pan cytokeratin stains, pan melanocytic cocktail (hmb-45, anti-mart 1, anti-tyrosinase), s100, ae1/ae3, p63, smooth muscle actin, cd31, and cd34 to exclude other neoplasms. 1-3 while soft tissue sarcomas are graded based on histological appearance, this is not appropriate for afx because the alarmingly abnormal features would suggest a highgrade tumor although it has intermediate malignant potential at most. 2 mohs micrographic surgery has been shown to be the standard of care in the treatment of afx, replacing wide-margin excision. 2,11,12 recurrence rates of afx have been up to discussion skin november 2017 volume #1 issue #3 copyright 2017 the national society for cutaneous medicine 172 6% using mohs surgical techniques in comparison with 16% recurrence associated with wide-margin excision. 2 afx has an excellent prognosis, though there have been rare cases of metastatic disease. 1,2,6,10 metastatic spread is so rare that it has been suggested that cases of metastatic afx were misdiagnosed cases of undifferentiated pleomorphic sarcoma. 2 despite low recurrence rates, follow up at 6 month intervals is recommended to check for recurrence, healing at the excision site, lymphadenopathy, and other skin cancers, as these patients have a history of aggressive sun damage. 2,10 conflict of interest: none disclosures: none. funding: none. corresponding author: timothy nyckowsky, bs 6000 university ave., #450 west des moines, ia 50266 847-791-4324 timothynyckowski@gmail.com references: 1. mentzel t, requena l, brenn t. atypical fibroxanthoma revisited. surg pathol clin. 2017 jun;10(2):319-335. 2. iorizzo lj 3rd, brown md. atypical fibroxanthoma: a review of the literature. dermatol surg. 2011 feb;37(2):146-57. 3. beer tw, drury p, heenan pj. atypical fibroxanthoma: a histological and immunohistochemical review of 171 cases. am j dermatopathol. 2010 aug;32(6):533-40. 4. helwig eb. atypical fibroxanthoma, in tumor seminar: proceedings of 18th annual seminar of san antonio society of pathologists, 1961. tex j med 1963;59:664–7. 5. anderson hl, joseph ak. a pilot feasibility study of a rare skin tumor database. dermatol surg. 2007 jun;33(6):693-6. 6. nguyen cm, chong k, cassarino d. clear cell atypical fibroxanthoma: a case report and review of the literature. j cutan pathol. 2016 jun;43(6):538-542. 7. murali r, palfreeman s. clear cell atypical fibroxanthoma report of a case with review of the literature. j cutan pathol. 2006 may;33(5):343-8. 8. fretzin df, helwig eb. atypical fibroxanthoma of the skin. a clinicopathologic study of 140 cases. cancer. 1973 jun;31(6):1541-52. 9. goette dk, odom rb. atypical fibroxanthoma masquerading as pyogenic granuloma. arch dermatol. 1976 aug;112(8):1155-7. 10. pesapane f, nazzaro g, lunardon l, coggi a, gianotti r. two friends with eroded nodules on the ears: atypical fibroxanthoma case report. an bras dermatol. 2015 jul-aug;90(4):577-9. 11. chilukuri s, alam m, goldberg lh. two atypical fibroxanthomas of the ear. dermatol surg. 2003 apr;29(4):408-10. 12. zogbi l, juliano c, neutzling a. atypical fibroxanthoma†. j surg case rep. 2015 mar 4;2015(3) skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 328 brief articles nab-paclitaxel/gemcitabine induced acquired ichthyosis adriana lopez baa, joel shugar mdb, and mark lebwohl mdc acolumbia university vagelos college of physicians and surgeons, new york, ny bicahn school of medicine at mount sinai, department of otolaryngology, new york, ny cicahn school of medicine at mount sinai, department of dermatology, new york, ny acquired ichythyosis (ai) is an uncommon non-inherited cutaneous disorder of abnormal keratinization that is most frequently associated with underlying malignancy. drug induced ai is uncommon and has been rarely linked to chemotherapeutic agents. herein, we report the case of a man with pancreatic adenocarcinoma who developed an ichthyosiform eruption upon starting chemotherapy with nab-paclitaxel plus gemcitabine. a 70-year-old male physician with a history of stage ii pancreatic adenocarcinoma presented for evaluation of lower extremity swelling and progressive dry, flaky skin. ten months prior, the patient was first seen for recurrent, self-healing, pruritic erythematous papules. punch biopsy was performed which showed an atypical cellular infiltrate of scattered large cd30+ cells with clonal t-cell receptor-β gene rearrangement. though the clinicopathologic diagnosis was most consistent with lymphomatoid papulosis (lyp), imaging was pursued to exclude extracutaneous lymphoproliferative disease. ct scan incidentally detected a mass in the body of the pancreas and biopsy was concordant with pancreatic adenocarcinoma. the patient was otherwise healthy with no medical problems and did not take any medications. within the first few weeks of starting chemotherapy with nab-paclitaxel plus gemcitabine, the patient reported new onset lower extremity swelling and skin redness. lower extremity doppler ultrasound was the ichthyoses are a diverse group of cutaneous disorders characterized by abnormalities in cornification. the majority of ichthyoses are inherited with childhood presentation and new onset ichthyosis in adulthood warrants further medical evaluation. though most well recognized for its association with hodgkin’s disease, acquired ichthyosis (ai) has been linked to a number of inflammatory, autoimmune, and endocrine processes. however, druginduced ai is exceedingly rare and remains a poorly understood entity. here we report a case of a male patient who developed ai while receiving nab-paclitaxel plus gemcitabine for treatment of pancreatic adenocarcinoma. abstract introduction case report skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 329 negative for deep vein thrombosis (dvt) and the patient denied any previous history of leg swelling. shortly thereafter he noted progressive non-pruritic, dry, scaly skin, on the legs that was unresponsive to intensive moisturization. after 3 months of medical treatment, pancreatectomy was performed which was followed by adjuvant chemotherapy, again with nab-paclitaxel plus gemcitabine. in the perioperative period during which chemotherapy was held, the patient noted reduced lower extremity swelling and decreased skin dryness on his legs. at the time of presentation, the patient was in his fourth month of adjuvant chemotherapy. upon resuming treatment, the patient noted that the leg swelling had returned and his skin had become dry with thick scale. physical exam was notable for bilateral lower extremity pitting edema and erythema with overlying thick, brown, geometric scales on the anterior tibias (figure 1). lower extremity venous ultrasound was again negative for dvt. clinical presentation, within the context of patient history, was most consistent with drug induced acquired ichthyosis and the patient was started on clobetasol ointment. the ichthyoses are a heterogeneous group of cutaneous disorders that can be acquired or congenital. ichthyosis vulgaris (iv), the most common inherited ichthyosis, is a benign dermatologic condition due to loss of function mutations in the filaggrin (flg) gene. flg protein is critical for normal epidermal homeostasis and proper skin barrier function.1 iv typically arises in childhood and is characterized by chronic skin scaling, usually affecting the abdomen and extensor surfaces of the extremities. figure 1: ichthyosiform plate-like, brown patches with scale on the right anterior lower leg.patient history, was most consistent with drug induced ai and the patient was started on clobetasol ointment. while physical exam findings of ai can be virtually identical to that of iv, ai develops in adulthood and is frequently associated with underlying systemic disease.2 ai has been correlated with several conditions including hyperparathyroidism3, malnutrition4 and lyp5; however, it is most commonly observed as a paraneoplastic syndrome in hodgkin’s disease.6 chemotherapy associated ai has rarely been described with the majority of documented cases confined to one study. of 74 hospitalized patients evaluated for mucocutaneous complications of chemotherapy, ai was reported in patients treated with doxorubicin (n=11), cytarabine discussion skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 330 (n=10), cisplatin (n=4), cyclophosphamide (n=3), etoposide (n=3), vincristine (n=3), gemcitabine (n=2), hydroxyurea (n=2), aminocamptothecin (n=1), mitomycin (n=1), mitoxanthrone (n=1), vinblastine (n=1), bleomycin (n=1), carboplatin (n=1), and docetaxel (n=1).7 interpretation of this data is however difficult as no patient received monotherapy and drug regimens were not specified. other than the aforementioned drugs, ponatinib is the only other chemotherapeutic agent reported in association with ai.8 within the context of this patient, there were several considerations regarding the etiology of ai. paraneoplastic ai was considered less likely as skin changes most frequently coincide or precede the diagnosis of malignancy and generally improve, not worsen, with treatment.2 the possibility of ai due to malabsorption was also felt to be unlikely as there was no evidence of such before or after pancreatectomy. the patient’s recent diagnosis of lyp was somewhat interesting as lyp has been previously associated with ai.5 however, given the temporal association of chemotherapy administration and development of ai, we feel this most strongly supports the assumption that ai was chemotherapyinduced. since this patient was treated with nabpaclitaxel plus gemcitabine, it is impossible to determine if one or both drugs were contributory. though uncommon, gemcitabine has been associated with the development of acute lipodermatosclerosislike or “pseudocellulitis” reactions.9 the pathophysiology of this reaction is unknown but underlying defects in lymphatic drainage have been suggested as the inciting factor. subsequent accumulation of fluid in the interstitial space could lead to drug accumulation in subcutaneous tissue and localized dermatologic toxicity due to impaired drug inactivation.10 similar to this case, patients typically present with acute onset lower extremity swelling, erythema, and hyperpigmentation over the anterior tibia.9 nab-paclitaxel is an albumin-bound formulation of paclitaxel and belongs to the taxane family of drugs which have been shown to upregulate the production of various cytokines, including tumor necrosis factor-α (tnf-α).11 overexpression of tnf-α has been associated with defects in normal skin barrier formation and has been extensively studied in psoriasis.1 pathologic expression of tnf-α has been correlated with impaired synthesis of skin barrier proteins including flg and loricin – both of which are needed for normal formation of the stratum corneum.1 we can only speculate about whether gemcitabine, nab-paclitaxel or the combination of both resulted in the development of ai in this patient. it is possible that gemcitabine caused alterations in vascular permeability which altered the inflammatory microenvironement, leading to localized defective tissue repair and keratinocyte dysfunction. with increased fluid extravasation into the subcutaneous tissue, the overlying skin may have been more susceptible to the effects enhanced tnf-α expression, resulting in impaired skin barrier function. interestingly, it has been shown that patients with pancreatic cancer frequently have increased levels of tnf-α, and thus this may also have played a role.12 it is presently unclear how gemcitabine, nab-paclitaxel, and systemic cytokine dysregulation may interact to produce ai and additional research is warranted. conflict of interest disclosures: none. funding: none. skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 331 corresponding author: mark lebwohl 5 east 98th street, 5th floor new york, ny 10029 phone: (212) 241-9728 email: mark.lebwohl@mountsinai.org references: 1. kim be, howell md, guttman-yassky e, et al. tnf-alpha downregulates filaggrin and loricrin through c-jun n-terminal kinase: role for tnf-alpha antagonists to improve skin barrier. j invest dermatol. 2011;131(6):12721279. 2. patel n, spencer la, english jc, iii, zirwas mj. acquired ichthyosis. journal of the american academy of dermatology. 2006;55(4):647-656. 3. london rd, lebwohl m. acquired ichthyosis and hyperparathyroidism. journal of the american academy of dermatology. 1989;21(4 pt 1):801-802. 4. dykes pj, marks r. acquired ichthyosis: multiple causes for an acquired generalized disturbance in desquamation. british journal of dermatology. 1977;97(3):327-334. 5. yokote r, iwatsuki k, hashizume h, takigawa m. lymphomatoid papulosis associated with acquired ichthyosis. journal of the american academy of dermatology. 1994;30(5):889-892. 6. aram h. acquired ichthyosis and related conditions. int j dermatol. 1984;23(7):458-461. 7. chiewchanvit s, noppakun k, kanchanarattanakorn k. mucocutaneous complications of chemotherapy in 74 patients from maharaj nakorn chiang mai hospital. journal of the medical association of thailand = chotmaihet thangphaet. 2004;87(5):508514. 8. alloo a, sheu j, butrynski je, et al. ponatinib ‐ induced pityriasiform, folliculocentric and ichthyosiform cutaneous toxicities. british journal of dermatology. 2015;173(2):574-577. 9. mittal a, leventhal js. gemcitabineassociated acute lipodermatosclerosislike eruption: an underrecognized phenomenon. jaad case reports. 2017;3(3):190-195. 10. curtis s, hong s, gucalp r, calvo m. gemcitabine-induced pseudocellulitis in a patient with recurrent lymphedema: a case report and review of the current literature. american journal of therapeutics. 2016;23(1):e321-323. 11. bogdan c, ding a. taxol, a microtubulestabilizing antineoplastic agent, induces expression of tumor necrosis factor alpha and interleukin-1 in macrophages. j leukoc biol. 1992;52(1):119-121. 12. dima so, tanase c, albulescu r, et al. an exploratory study of inflammatory cytokines as prognostic biomarkers in patients with ductal pancreatic adenocarcinoma. pancreas. 2012;41(7):1001-1007. mailto:mark.lebwohl@mountsinai.org skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 916 brief article case of generalized granuloma annulare treated with low dose naltrexone + puva taylor e. gladys, md, mba1, taehan kim, md, phd2, colleen j. beatty, md2, sonal choudhary, md2 1 university hospitals cleveland medical center department of dermatology, cleveland, oh 2 university of pittsburgh medical center department of dermatology, pittsburgh, pa granuloma annulare (ga) is a common, noninfectious granulomatous skin condition presenting more frequently in women.1.2 although the etiology is unclear, histologic features suggest it may be related to a delayed hypersensitivity reaction. ga typically presents in its localized form, characterized by flesh-colored to erythematous papules coalescing into annular plaques without scale, most commonly on the dorsal hands.1-3 lesions can be pruritic and often resolve without treatment in two years.1-3 generalized ga presents with similar morphology, but with >10 lesions or in a widespread distribution affecting the head, neck, trunk, and limbs. 1-3 representing about 8-15% cases, it is known to be more symptomatic, longer-lasting, and recalcitrant to treatment.1-3 the diagnosis is made based on clinicopathological correlation with palisading abstract granuloma annulare (ga) is a common, noninfectious granulomatous skin condition that usually presents in its localized form, characterized by flesh-colored to erythematous papules coalescing into annular plaques without scale, commonly on the dorsal hands. lesions can be pruritic and often resolve without treatment in two years. however, the generalized form of ga has a lower incidence and presents with similar morphology, but with >10 lesions in a widespread distribution. generalized ga is known to be more symptomatic, longer lasting, and recalcitrant to treatment. the diagnosis is made based on clinicopathological correlation with palisading granulomas around degenerated collagen in the dermis, mucin, and infiltrative lymphocytes and histiocytes. treatment remains challenging as evidence is limited to case reports, case series, and a few retrospective studies. here we present the case of a 59-yearold caucasian female with pruritic rash that began on her abdomen and spread to her extremities over two months. biopsy revealed superficial histiocytic infiltrates palisading around eosinophilic areas of altered collagen, multiple multinucleate giant cells with elastophagocytosis and lymphohistiocytic perivascular infiltrates, and mucin in the dermis on colloidal iron staining. overall, this was consistent with generalized ga. the patient was started on a combination of low dose naltrexone (ldn) and psoralen and ultraviolet a (puva) therapy. at a five-month follow up visit, she demonstrated near complete resolution of symptoms without any serious adverse effects. introduction skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 917 figure 1. generalized granuloma annulare presenting as erythematous papules coalescing on medial aspect of left arm (a) and left abdomen (b). granuloma annulare status post five months of treatment of ldn + puva showing light pink patches on the medial aspect of the left arm (c) and left abdomen (d). figure 2. biopsy of granuloma annulare (a) demonstrating superficial histiocytic infiltrates with palisading surrounding eosinophilic areas of altered collagen (hematoxylin-eosin stain; original magnification: x4) and (b) colloidal iron stain revealing mucin in the dermis. skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 918 granulomas around degenerated collagen in the dermis, mucin, and infiltrative lymphocytes and histiocytes.1,2 suggested yet controversial disease associations include dyslipidemia, diabetes mellitus, malignancy, thyroid disease and infections including human immunodeficiency, hepatitis b, and hepatitis c viruses.1,2 treatment remains challenging as evidence is limited to case reports, case series, and a few retrospective studies.1-3 several treatments have been proposed, including topical or intralesional steroids, cryosurgery, photodynamic therapy, narrowband uvb light therapy, and fumaric acid (not available in the us), but none have been proven to be consistently effective.1,2 a 59-year-old caucasian female presented with a pruritic rash that began on her left lower abdomen and spread to her extremities over two months. physical exam revealed numerous erythematous papules and plaques, coalescing into annular distributions over the trunk and arms without scale (figure 1a-b). a biopsy demonstrated superficial histiocytic infiltrates palisading around eosinophilic areas of altered collagen, and multiple multinucleate giant cells with elastophagocytosis and lymphohistiocytic perivascular infiltrates (figure 2a). a colloidal iron stain showed mucin in the dermis (figure 2b). overall, this was most consistent with generalized ga. treatment was started with topical clobetasol 0.05% with a plan to start hydroxychloroquine. unfortunately, the patient was found to have latent tuberculosis and started on a two-month course of rifampin instead. during this time, she continued to suffer with pruritis and dyspigmentation from topical steroid use. the patient was then trialed on low dose naltrexone (ldn), 1 mg daily for two weeks, escalated to 2.5 mg daily for two weeks, and then held continuously at 4.5 mg daily. once on the dose of ldn at 4.5 mg, she began puva treatments, twice weekly. at the fivemonth follow-up visit after 16 sessions of puva, her ga lesions had radically improved and her associated pruritis had completely resolved (figure 1c-d). her only side effect was occasional vivid dreams. naltrexone is a non-selective competitive opioid receptor antagonist used to treat substance use disorders at a 50 mg-100 mg dose.4-6 at this dose, naltrexone completely blocks opioid receptors leading to a proinflammatory response. however, at doses of ldn (1-5 mg), naltrexone causes only a partial blockade, leading to receptor upregulation and release of anti-inflammatory molecules, such as β-endorphin and enkephalin.5 secondarily, naltrexone acts as an antagonist at toll-like receptor 4, reducing glial and macrophage inflammatory release of cytokines.4-6 several cells of the skin express opioid receptors including keratinocytes, melanocytes, fibroblasts and some adnexal structures.6 there have also been increasing reports of ldn’s ability to reduce pruritis in other dermatologic conditions, perhaps due to inhibition of basophilic histamine release.6 studies have found success in hailey-hailey disease, systemic sclerosis, guttate psoriasis, and lichen planopilaris, as well as a host of diseases affecting other body systems.5,6 side effects include vivid dreams, insomnia, headache, and anxiety. to date, case report discussion skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 919 however, no serious adverse effects have been reported. 4-6 in addition to ldn, this patient received puva therapy. studies have demonstrated mixed results on the efficacy of puva on ga.3,7 in a retrospective study, browne et al determined that puva was successful in clearance or at least improvement in 66% of 44 cases of generalized ga.7 cunningham and colleagues supported this finding with a small cohort of 8 out of 12 patients experiencing total or near total clearance of generalized ga.3 adverse effects of puva include phototoxicity, nail damage, nausea, and reactivation of hsv in the short-term, while long-term treatment has been associated with development of lentigines and keratoses, increased risk of squamous cell carcinoma, and altered immune function.8 ldn plus puva should be considered an alternative treatment for generalized ga. this case demonstrates that although the mechanism is unclear, the combined therapy led to improvements in cutaneous manifestations and associated pruritis with few side effects. a further investigation in larger cohorts is needed to explore the therapeutic potential of ldn plus puva in this treatment-refractory condition. conflict of interest disclosures: none funding: none corresponding author: sonal choudhary, md university of pittsburgh medical center 3708 fifth avenue pittsburgh, pa 15213 email: choudharys@upmc.edu references: 1. thornsberry la, english jc 3rd. etiology, diagnosis, and therapeutic management of granuloma annulare: an update. am j clin dermatol. 2013 aug;14(4):279-90. doi: 10.1007/s40257-013-0029-5. pmid: 23696233. 2. nordmann tm, kim jr, dummer r, anzengruber f. a monocentric, retrospective analysis of 61 patients with generalized granuloma annulare. dermatology. 2020 may; 236(4): 369-74. doi: 10.1159/000507247. pmid: 32403113. 3. cunningham l, kirby b, lally a, collins p. the efficacy of puva and narrowband uvb phototherapy in the management of generalized granuloma annulare. j dermatolog treat. 2016 mar; 27(2): 136-39. doi: 10.3109/09546634.2015.1087461 4. toljan k, vrooman b. low-dose naltrexone (ldn) – review of therapeutic utilization. med sci (basel). 2018 dec; 6(4): 82. doi: 10.3390/medsci6040082. pmid: 30248938 5. jaros j, lio p. low dose naltrexone in dermatology. j drugs dermatol. 2019 mar; 18(3):235-238. pmid: 30909326. 6. ekelem c, juhasz m, khera p, mesinkovska na. utility of naltrexone treatment for chronic inflammatory dermatologic conditions. jama dermatol. 2019 feb; 155(2):229-236. doi: 10.1001/jamadermatol.2018.4093 7. browne f, turner d, goulden v. psoralen and ultraviolet a in the treatment of granuloma annulare. 2011 apr; 27(2): 81-84. doi: 10.1111/j.1600-0781.2011.00574.x 8. rathod dg, muneer h, masood s. phototherapy. 2021 jul 20. in: statpearls [internet]. treasure island (fl): statpearls publishing; 2021 jan; pmid: 33085287. conclusion selective inhibition of tyrosine kinase 2 with deucravacitinib (bms-986165) compared with janus kinase 1−3 inhibitors anjaneya chimalakonda, james burke,* lihong cheng, ian catlett, aditya patel, jun shen, ihab g. girgis, subhashis banerjee, john throup bristol myers squibb, princeton, nj, usa *employee at the time the analysis was conducted. background • tyrosine kinase 2 (tyk2), an intracellular kinase involved in the pathogenesis of immune-mediated inflammatory diseases (imids), regulates signaling and functional responses downstream of the interleukin (il)-12, il-23, and type i interferon receptors1 • deucravacitinib (bms-986165) is an oral, selective, allosteric tyk2 inhibitor with a unique mode of binding to the less-well-conserved pseudokinase domain rather than to the conserved active site in the catalytic domain1 — this unique mode of binding provides high functional selectivity for tyk2 vs other tyrosine kinases in cellular and other in vitro assays1 — allosteric inhibition may provide robust efficacy and a differentiated safety profile vs other kinases due to decreased toxicity • in a 12-week, placebo-controlled, phase 2 trial in patients with moderate to severe plaque psoriasis, the proportion of patients who achieved a 75% or greater improvement from baseline in the psoriasis area and severity index (pasi 75) at week 12 (primary endpoint) was significantly higher with deucravacitinib 3 mg twice daily (bid; 69%), 6 mg bid (67%), and 12 mg once daily (qd; 75%) vs placebo (7%; p<0.001).2 deucravacitinib also had a favorable safety profile including no significant changes in laboratory parameters2 • deucravacitinib is currently being evaluated in multiple imids including plaque psoriasis, psoriatic arthritis, inflammatory bowel disease, and lupus objective • to compare the selectivity of deucravacitinib vs the approved janus kinase (jak) inhibitors tofacitinib, upadacitinib, and baricitinib, at clinically relevant doses and plasma concentrations methods • in vitro whole blood assays that measure activity of tyk2, jak 1/3, and jak2 pathways were developed (table 1) • half-maximal inhibition concentrations (ic50) of deucravacitinib, tofacitinib, upadacitinib, and baricitinib were determined using these assays, as well as hill coefficients for inhibition table 1. in vitro whole blood assays for jak 1−3 and tyk2 inhibitors signaling kinase stimulant endpoint jak 1/3 il-2 stat5 phosphorylation in t cells jak2 tpo stat3 phosphorylation in platelets tyk2 il-12 ifn-γ production in cells ifn, interferon; il, interleukin; jak, janus kinase; stat, signal transducer and activator of transcription; tpo, thrombopoietin; tyk, tyrosine kinase. • pharmacokinetic (pk) profiles were simulated using parameters derived from published population pk models for tofacitinib, upadacitinib, and baricitinib3-6 and from internal analyses for deucravacitinib — pk parameters, including maximum plasma concentration (cmax), average plasma concentration (cave), and minimum plasma concentration (cmin), were calculated • plasma concentrations of deucravacitinib, tofacitinib, upadacitinib, and baricitinib were plotted relative to their whole blood ic50 values — if the whole blood ic50 value was higher than the cmax value, the fold difference between the ic50 and cmax values was calculated • additionally, key exposure parameters (cmax, cave, and cmin) of these agents were plotted relative to their individual whole blood ic50 values • average percent inhibition of jak 1−3 and tyk2 signaling was calculated using the following equation based on the average drug concentration, whole blood ic50, and the hill coefficient — percent inhibition = 100/(1+[(ic50/x)^h]) where x is the average drug concentration and h is the hill coefficient • given that in vitro assays were conducted in whole blood, no adjustments for plasma protein binding differences were considered in this evaluation. additionally, the blood to plasma concentration ratio of these agents is close to 1 (range, 1.16−1.32).7 therefore, no adjustments were considered conclusions • this analysis confirms that deucravacitinib is a highly selective, allosteric tyk2 inhibitor with minimal or no activity against jak 1−3 • selective tyk2 inhibition is consistent with the reduced potential for treatment-related toxicities (eg, laboratory parameter abnormalities, gut perforation, thrombosis) in deucravacitinib-treated patients, effects generally associated with jak 1−3 inhibitors2,10,11 • conversely, the jak 1−3 inhibitors included in this analysis (tofacitinib, upadacitinib, and baricitinib) did not exhibit tyk2 inhibition. hence, the undesirable adverse effects associated with these agents as noted above are unlikely to be related to tyk2 inhibition • these results suggest that deucravacitinib is in a distinct therapeutic class compared with inhibitors of the closely related intracellular signaling kinases, jaks 1−3 • ongoing trials in plaque psoriasis (nct03624127, nct03611751, nct04167462, nct03924427, and nct04036435) and other imids will provide additional safety information about deucravacitinib presented at the 2020 fall clinical dermatology conference; october 29−november 1; virtual meeting and at las vegas, nevada http://www.globalbmsmedinfo.com this poster may not be reproduced without written permission from the author of this poster. results in vitro whole blood ic50 • based on in vitro whole blood ic50 values (table 2), deucravacitinib had greater selectivity for tyk2 compared with jak 1/3 or jak2 • in contrast, tofacitinib, upadacitinib, and baricitinib demonstrate more potent inhibition of jak 1/3 and jak2 compared with tyk2. whole blood ic50 values for tofacitinib, upadacitinib, and baricitinib are within range of values reported in the published literature8 table 2. in vitro whole blood ic50 values for jak 1−3 and tyk2 inhibitors whole blood ic50 (95% ci), nm signaling kinase readout tofacitinib baricitinib upadacitinib deucravacitinib jak 1/3 (il-2−induced pstat5) 17 (15−19) 11 (8.7−13) 7.8 (6.5−9.5) 1646 (1446−1872) jak2 (tpo−induced pstat3) 217 (182−258) 32 (28−36) 41 (36−47) >10,000 (—) tyk2 (il-12−induced ifn-γ release) 5059 (3767−7026) 2351 (1834−2980) 3685 (2346−6208) 40 (29−55) ic50, half-maximal inhibitory concentration; ifn, interferon; il, interleukin; jak, janus kinase; stat, signal transducer and activator of transcription; tpo, thrombopoietin; tyk, tyrosine kinase. daily percent inhibition by jak 1−3 and tyk2 inhibitors • at clinically relevant concentrations, deucravacitinib inhibited tyk2 by >50% over 24 hours and exerted minimal effects (<2% inhibition) against jak 1−3 (figure 1). this indicates that deucravacitinib is a selective tyk2 inhibitor and does not modulate the jak 1−3 pathways • tofacitinib, upadacitinib, and baricitinib exhibited varying degrees of inhibition against jak 1/3 (daily average inhibition, 70%−94%) and jak2 (23%−67%) and no meaningful inhibition against tyk2 (<2%) figure 1. daily percent inhibition by jak 1−3 and tyk2 inhibitors 0 25 50 75 100 2 mg 4 mg 5 mg 10 mg 15 mg 30 mg 6 mg qd 12 mg qd d ai ly i n h ib it io n , % jak 1/3 jak2 tyk2 baricitinib tofacitinib upadacitinib deucravacitinib (tyk2i) jak, janus kinase; qd, once daily; tyk2i, tyrosine kinase 2 inhibitor. jak 1−3 and tyk2 inhibitor plasma concentrations and whole blood ic50 • at clinically relevant doses, deucravacitinib plasma concentrations were higher than the tyk2 whole blood ic50 value for a considerable portion (8−16 hours) of the 24-hour dosing interval and considerably lower than the jak 1−3 ic50 values throughout the dosing interval (figure 2) • deucravacitinib cmax values remained approximately 9to 18-fold lower than the jak 1/3 ic50 and approximately >52to 109-fold lower than the jak2 ic50. in contrast, tofacitinib, upadacitinib, and baricitinib plasma concentrations were higher than jak 1/3 ic50 values over most of the dosing interval but were considerably lower than tyk2 ic50 values • additionally, upadacitinib and baricitinib plasma concentrations exceeded jak2 ic50 values over part of the dosing interval, especially at higher doses figure 2. jak 1−3 and tyk2 inhibitor plasma concentrations over time and whole blood ic50 17-fold 31-fold 33-fold 9-fold >52-fold 10 100 1000 10,000 0 6 12 18 24 p la sm a co n ce n tr at io n ( n m ) time (hours) 10 100 1000 10,000 0 6 12 18 24 p la sm a co n ce n tr at io n ( n m ) time (hours) 0 6 12 18 24 p la sm a co n ce n tr at io n ( n m ) time (hours) 10 100 1000 10,000 0 6 12 18 24 p la sm a co n ce n tr at io n ( n m ) time (hours) 1 10 100 1000 10,000 baricitinib tofacitinib upadacitinib deucravacitinib (tyk2) jak 1/3 ic50 jak2 ic50 tyk2 ic50 jak 1/3 ic50 jak2 ic50 tyk2 ic50 jak 1/3 ic50 jak2 ic50 tyk2 ic50 jak 1/3 ic50 jak2 ic50 tyk2 ic50 5 mg bid 15 mg qd2 mg qd 6 mg qd 10 mg bid 30 mg qd4 mg qd 12 mg qd arrows and fold-increase values pertain to the highest approved dose for each agent. tofacitinib 10 mg bid is approved for treating ulcerative colitis but not for rheumatoid arthritis.9 tofacitinib, upadacitinib, and baricitinib: margins to tyk2 inhibitor ic50 are provided for the highest approved dose. bid, twice daily; ic50, half-maximal inhibitory concentration; jak, janus kinase; qd, once daily; tyk, tyrosine kinase 2. jak 1−3 and tyk2 inhibitor pharmacokinetic parameters and whole blood ic50 • at clinically relevant doses, deucravacitinib cmax, cave, and cmin were higher than or close to the tyk2 ic50 value, but were considerably lower than jak 1/3 and jak2 ic50 values (figure 3) • cmax, cave, and cmin values for tofacitinib, upadacitinib, and baricitinib were many-fold lower than tyk2 ic50 values, but were above or within range of jak 1/3 and jak2 ic50 values figure 3. jak 1−3 and tyk2 inhibitor pharmacokinetic parameters and whole blood ic50 1 10 100 1000 10,000 cmax (nm) cave (nm) cmin (nm) p la sm a co n ce n tr at io n ( n m ) 2 mg qd 4 mg qd jak 1/3 ic50 jak2 ic50 tyk2 ic50 1 10 100 1000 10,000 cmax (nm) cave (nm) cmin (nm) p la sm a co n ce n tr at io n ( n m ) 5 mg qd 10 mg qd jak 1/3 ic50 jak2 ic50 tyk2 ic50 1 10 100 1000 10,000 cmax (nm) cave (nm) cmin (nm) p la sm a co n ce n tr at io n ( n m ) 15 mg qd 30 mg qd jak 1/3 ic50 jak2 ic50 tyk2 ic50 1 10 100 1000 10,000 cmax (nm) cave (nm) cmin (nm) p la sm a co n ce n tr at io n ( n m ) 6 mg qd 12 mg qd jak 1/3 ic50 jak2 ic50 tyk2 ic50 baricitinib tofacitinib upadacitinib deucravacitinib tyk2 bid, twice daily; cave, average plasma concentration; cmax, maximum plasma concentration; cmin, minimum or trough plasma concentration; ic50, half-maximal inhibitory concentration; jak, janus kinase; qd, once daily; tyk2i, tyrosine kinase 2 inhibitor. references 1. burke jr et al. sci transl med. 2019;11:1-16. 2. papp k et al. n engl j med. 2018;379:1313-1321. 3. girgis ig et al. presented at: triennial meeting of the skin inflammation and psoriasis international network; april 25-27, 2019; paris, france. 4. klünder b et al. clin pharmacokinet. 2019;58:1045-1058. 5. xie r et al. int j clin pharmacol ther. 2019;57:464473. 6. zhang x et al. cpt pharmacometrics syst pharmacol. 2017;6:804-813. 7. dowty me et al. pharmacol res perspect. 2019;7:e00537. 8. mcinnes ib et al. arthritis res ther. 2019;21:183. 9. xeljanz [package insert]. new york, ny: pfizer inc.; 2019. 10. winthrop kl. nat rev rheumatol. 2017;13:234-243. 11. gadina m et al. rheumatology (oxford). 2019;58:i4-i16. acknowledgments • this analysis was sponsored by bristol myers squibb. professional medical writing from ann marie fitzmaurice, phd and editorial assistance were provided by peloton advantage, llc, an open health company, parsippany, nj, and were funded by bristol myers squibb relationships and activities • ac, lc, js, ic, ap, igg, sb, jt are employees and shareholders of bristol myers squibb; jb was an employee and shareholder of bristol myers squibb at the time the analysis was conducted skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 98 brief articles geometric facial erosions on a newborn shelby stribling, ba1, matthew lacour, bs1, lindy ross, md1, sharon raimer, md1, brent kelly, md1 1department of dermatology, university of texas medical branch, galveston, tx a two-day old african american female presented with abnormal skin findings present at birth. she was born at 38 weeks and 1 day by spontaneous vaginal delivery with apgars of 7 and 8 at one and five minutes. the infant’s mother had a past medical history of type ii diabetes mellitus, av block, eczema, schizoaffective/bipolar disorder, possible first trimester illicit drug use, and syphilis treated in 2006. there was no family history of congenital defects. upon examination of the patient, sharply demarcated erosions were present on the bilateral cheeks with scalloped, geometric borders (figure 1), as well as erosions on the intertriginous areas of the neck and a small figure 1: bilateral geometric facial erosions on the cheeks of a newborn present at the time of birth. when a newborn exhibits dermal aplasia and linear erosions on the face and neck, especially if there are ocular anomalies, further investigation is needed to determine if he or she has midas (microphthalmia, dermal aplasia, and sclerocornea) or other syndromes with associated skin findings. midas syndrome or mls (microphthalmia with linear skin defect) is an x-linked dominant genodematosis characterized by cutaneous, ocular, central nervous system, and cardiac defects. it is essential to diagnose midas syndrome early in life to allow for a thorough workup. this workup is to determine if there are any associated abnormalities in the child that require a multidisciplinary approach for diagnosis and treatment. while the skin lesions of midas syndrome heal spontaneously, other associated abnormalities require early intervention and can be life threatening. this case report describes the work up, diagnosis, etiology, potential complications, and necessary follow up of midas syndrome in a new born african american female. abstract case report skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 99 figure 2: right sided micropthalmia and corneal opacity. figure 3: skin biopsy of an eroded plaque (hematoxylin-eosin stain, original magnification x 100). eroded macule on the left labia majora. a wound culture of the skin lesions was negative, and bacitracin was applied by the pediatric team. other notable findings on exam included left micropthalmia and bilateral corneal opacities (figure 2). also, on the first day of life, a 3 x 3 cm occipital encephalocele containing a small tongue of cerebellar tissue and abnormal venous structures was repaired. the biopsy specimen showed upper epidermal pallor and minimal perivascular lymphocytic infiltration with no evidence of lupus or primary bullous disorder (figure 3). epidermal pallor can be a nonspecific histological finding and may present in the setting of various nutritional deficiencies. this diagnosis was considered, but it was thought to be less likely in this patient who was receiving good nutritional support and had normal laboratory values. laboratory studies were negative for anti-ssa and anti-ssb; serum zinc and albumin were within normal limits as were newborn screening test results. chromosomal microarray analysis revealed a 8,165 kbp loss of chromosome xp22.32p22.2, which is consistent with midas syndrome. midas syndrome (microphthalmia, dermal aplasia, and sclerocornea) or mls (microphthalmia with linear skin defect) is an x-linked dominant condition first described in the early 1990s. midas syndrome displays great phenotypic variability in females while appearing to exhibit lethality in hemizygous males in utero. midas syndrome is most often caused by a deletion or translocation of xp22.3 encoding the gene hccs. hccs encodes the mitochondrial holocytochrome c type synthase that is involved in complex iii of the mitochondrial respiratory chain (mrc) that carries out oxidative phosphorylation.1 a mutation of the cox7b gene at xq21.1 has been identified which encodes for cytochrome c oxidase or complex iv of oxidative phosphorylation. and is more commonly associated with patients who only exhibit the dermal aplasia of midas syndrome without ocular or other anomalies.2 however, there have been reported cases of midas syndrome with no mutations of the hccs and cox7b genes, but genetic analysis shows a skewed pattern of inactivation of the x chromosome.3 mosaicism of x chromosome inactivation is also believed to contribute to the vast array of phenotypic presentations of sporadic as well as heritable cases of midas syndrome.1,4 discussion skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 100 the linear skin lesions follow the blaschko lines, which form as embryonic cells migrate during fetal development. the skin findings of midas syndrome are typically confined to the face and neck region. dermatoscopic examination of the lesions reveals erythematous areas without evidence of sebaceous glands or vellus hair, and although the linear skin defects can appear to be erosions they actually represent profound atrophy of the skin and are similar but distinct from the dermal hypoplasia seen in goltz syndrome.5,6 while goltz syndrome presents with linear hyper and hypopigmented patches, skin involvement is not limited to the head and neck, and patients with this condition will also have fat herniation and skeletal abnormalities.6,7 aicardi syndrome can present with similar ocular and neurological features as midas syndrome but without the characteristic linear skin findings. all three of these diseases are xlinked with some overlap of clinical features which has led some authors to posit they may involve a contiguous region of the xp chromosome.8 with time, the dermal aplasia of midas syndrome heals with hyperpigmentation, and residual scarring can occur. microphthalmia is the most common associated ocular abnormality, and it can present unilaterally or bilaterally. additional documented ocular findings include sclerocornea, congenital glaucoma, retinal abnormalities, cataracts, microcornea, optic nerve hypoplasia, and anterior chamber defects. many other clinical features have been associated with midas syndrome such as central nervous system abnormalities like agenesis of the corpus callosum and microcephaly, speech and cognitive delay, genitourinary abnormalities, short stature, and cardiac defects with case reports of sudden cardiac death before one year of age.7,9 due to the many conditions that can be associated with midas syndrome, patients with this diagnosis should have full cardiac workup, mri of the brain, audiology testing, and ophthalmologic exam. when a newborn exhibits dermal aplasia on the face and neck, especially if there are ocular anomalies, further investigation is needed to determine if they have midas or other syndromes with associated skin findings. it is essential to diagnose midas syndrome early in life to allow for a thorough workup to determine if there are any associated abnormalities in the child that require treatment. while the skin lesions of midas syndrome heal spontaneously, other associated abnormalities require early intervention and can be life threatening.10 conflict of interest disclosures: none. funding: none. corresponding author: matthew lacour, bs university of texas medical branch galveston, tx mdlacour@utmb.edu references: 1. morleo m, pramparo t, perone l, et al. microphthalmia with linear skin defects (mls) syndrome: clinical, cytogenetic, and molecular characterization of 11 cases. american journal of medical genetics part a. 2005; 137a(2), 190-198. doi:10.1002/ajmg.a.30864. 2. rahden vav, rau i, fuchs s, et al. clinical spectrum of females with hccs mutation: from no clinical signs to a neonatal lethal form of the microphthalmia with linear skin defects (mls) syndrome. orphanet journal of rare diseases. 2014; 9 (1): 5353. doi:10.1186/1750-1172-9-53. mailto:lsross@utmb.edu skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 101 3. garcia-rabasco a, de-unamuno b, martinez f, febrer-bosch, alegre-demiquel v. microphthalmia with linear skin defects syndrome. pediatric dermatology. 2012; 30(6). doi:10.1111/j.15251470.2012.01735.x. 4. wimplinger i, rauch a, orth u, schwarzer u, trautmann u, kutsche k. mother and daughter with a terminal xp deletion: implication of chromosomal mosaicism and xinactivation in the high clinical variability of the microphthalmia with linear skin defects (mls) syndrome. european journal of medical genetics. 2007; 50(6):421-31. doi:10.1016/j.ejmg.2007.07.004 5. jr. hlda, rossi g, abreu lbd, bergamaschi c, silva abd, kutsche k. dermatoscopic aspects of the microphthalmia with linear skin defects (mls) syndrome. anais brasileiros de dermatologia. 2014; 89(1), 180-181. doi:10.1590/abd18064841.20142240. 6. happle r, daniels o, koopman, rjj. midas syndrome (micropthalmia, dermal aplasia, and sclerocornea): an x-linked phenotype distinct from goltz syndrome. american journal of medical genetics. 1993; 47(5):710-3. doi:10.1002/ajmg.1320470525. 7. carman kb, yakut a, sabuncu i, yarar c. midas (microphthalmia, dermal aplasia, sclerocornea) syndrome with central nervous system abnormalities. clinical dysmorphology. 2009;18(4), 234-5. doi:10.1097/mcd.0b013e32832e38a6. 8. naritomi k, izumikawa y, nagataki s, et al. combined goltz and aicardi syndromes in a terminal xp deletion: are they a contiguous gene syndrome? american journal of medical genetics. 1992; 43(5):839-43. doi:10.1002/ajmg.1320430517. 9. anguiano a, yang x, felix j, hoo j. twin brothers with midas syndrome and xx karyotype. american journal of medical genetics. 2003;119a(1):47-49. doi:10.1002/ajmg.a.10172. 10. morleo, m., franco, b. microphthalmia with linear skin defects syndrome. in: genereviews. seattle (wa): university of washington, seattle; 1993-2017. 2009 jun 18. background • pasdas, a validated composite index that assesses multiple facets of psa, including joints, dactylitis, enthesitis, and quality of life (qol),1 offers both a target and disease activity state assessment across important clinical domains with validated cutpoints2 (figure 1) • pasdas distinguishes treatment effect, performs better than traditional joint-only indices, and could be used as a treatment target in clinical trials and observational studies in psa1,3 figure 1. disease activity by pasdas score remission pasdas score ≤ 1.9 lda 1.9 < pasdas score < 3.2 moda 3.2 ≤ pasdas score < 5.4 hda pasdas score ≥ 5.4 4 6 820 hda, high disease activity; lda, low disease activity; moda, moderate disease activity; pasdas, psoriatic arthritis disease activity score • secukinumab is a fully human monoclonal antibody that selectively neutralizes interleukin-17a4 • secukinumab significantly improved multiple clinical domains of psa, including signs and symptoms, physical function, qol, and work productivity, over 104 weeks in the future 2 study (nct01752634)5 methods • this post-hoc analysis assessed the ability of secukinumab to achieve and sustain lda or remission by using pasdas through 104 weeks in the future 2 study results • baseline disease characteristics were well balanced across all treatment groups (table 1) table 1. baseline characteristics across groups6 characteristic mean (sd), unless otherwise stated secukinumab 300 mg s.c. (n = 100) secukinumab 150 mg s.c. (n = 100) placebo (n = 98) age, years 46.9 (12.6) 46.5 (11.7) 49.9 (12.5) female, n (%) 49 (49.0) 45 (45.0) 59 (60.2) time since first diagnosis of psa in years 7.4 (7.5) 6.5 (8.2) 7.3 (7.8) anti–tnf-naïve, n (%) 67 (67.0) 63 (63.0) 63 (64.3) psoriasis ≥ 3% of bsa, n (%) 41 (41.0) 58 (58.0) 43 (43.9) physician global vas 55.0 (14.7) 56.7 (16.6) 55.0 (16.0) patient global vas 60.7 (18.9) 62.0 (19.5) 57.6 (19.8) sf-36 pcs 36.9 (8.0) 36.2 (8.1) 37.4 (8.8) dactylitis count 3.6 (3.5) 4.5 (5.1) 2.7 (2.2) enthesitis count 2.8 (1.7) 3.2 (1.6) 3.1 (1.7) tjc (78 joints) 20.2 (13.3) 24.1 (19.4) 23.4 (19.0) sjc (76 joints) 11.2 (7.8) 11.9 (10.1) 12.1 (10.7) pasdas score 5.9 (0.9) 6.0 (1.0) 5.8 (1.0) n, number of randomized patients. bsa, body surface area; pasdas, psoriatic arthritis disease activity score; s.c., subcutaneous; sd, standard deviation; sf-36 pcs, short form-36 physical component summary; sjc, swollen joint count; tjc, total joint count; tnf, tumor necrosis factor; vas, visual analog scale figure 4. median core components of pasdas remission and lda patient global vasphysician global vas sjc 66 16 16 16 16 m ed ia n (q 1, q 3) s co re weeksweeks lda ldaremission lda remission remission lda remission weeksweeks m ed ia n (q 1, q 3) s co re m ed ia n (q 1, q 3) s co re m ed ia n (q 1, q 3) s co re 40 30 20 10 0 0 2 4 6 8 0 2 4 6 8 0 5 10 15 20 16 16104 104 1616 104104 104 104 104 104 tjc 68 n = 22 n = 22 n = 30 n = 30 n = 27 n = 27 n = 15 n = 15 n = 15 n = 15 n = 2 n = 2 n = 19 n = 19 n = 11 n = 11 n = 22 n = 22 n = 19 n = 19 n = 12 n = 12 n = 30 n = 30 n = 27 n = 27 n = 15 n = 15 n = 15 n = 15 n = 2 n = 2 n = 19 n = 19 n = 11 n = 11 n = 19 n = 19 n = 12 n = 12 secukinumab 300 mg s.c. secukinumab 150 mg s.c. placebo 16 1.0 0.8 0.6 0.4 0.2 0.0 65 60 55 50 45 40 weeksweeks lda ldaremission remission 161616 104104 104 104 16weeksweeks lda ldaremission remission 161616 104104 104 104 0.0 8 6 4 2 0 0.2 0.4 0.6 0.8 1.0 m ed ia n (q 1, q 3) c ou nt m ed ia n (q 1, q 3) s co re m ed ia n (q 1, q 3) s co re m ed ia n (q 1, q 3) le ve l leeds enthesitis tender dactylitis sf-36 pcsc-reactive protein (mg/l) n = 22 n = 22n = 19 n = 19n = 3 0 n = 30n = 2 7 n = 27 n = 15 n = 1 5 n = 15 n = 15 n = 2 n = 2 n = 19 n = 1 9 n = 11 n = 1 1 n = 12 n = 22 n = 19 n = 30 n = 27 n = 15 n = 15 n = 2 n = 19 n = 11 n = 12 n = 12 n = 22 n = 19 n = 30 n = 27 n = 15 n = 15 n = 2 n = 19 n = 11 n = 12 the median value is denoted by symbol in the figure while the upper and lower error bars represent third (q3) and first (q1) quartiles, respectively n, number of patients in respective disease states at assessment lda, low disease activity; pasdas, psoriatic arthritis disease activity score; q, quartile; sf-36 pcs, short form-36 physical component summary; sjc, swollen joint count; tjc, total joint count; vas, visual analog scale • tnf-naïve patients receiving secukinumab were more likely than tnf-ir patients to achieve pasdas remission and lda (figure 5a) • the proportion of patients achieving pasdas remission and lda with secukinumab was similar irrespective of time since first diagnosis of psa (figure 5b) • patients achieving pasdas remission and lda with secukinumab were significantly more likely to report improvement in psa qol, dermatology life quality index, health assessment questionnaire disability index (haq-di), and functional assessment of chronic illness therapy-fatigue scores than patients with hda (figure 6a) • patients achieving pasdas remission and lda with secukinumab reported significant improvements in measures of work productivity (figure 6b) figure 5. (a) pasdas remission and lda by anti–tnf exposure up to week 104; (b) effect of disease duration on pasdas remission and lda 27.7 20.6 14.0 12.9 16.7 13.3 38.2 47.2 32.1 8.3 18.5 22.2 3.5 9.7 2.8 0 29.1 17.0 10.7 8.3 0 10 20 30 40 50 60 70 80 150 mg (n = 63) placebo (n = 57) stneitap fo noitropor p 300 mg (n = 31) 150 mg (n = 36) placebo (n = 30) 150 mg (n = 24) 150 mg (n = 53) 300 mg (n = 55) 300 mg (n = 28) 300 mg (n = 65) week 16 anti−tnf-ir week 104 anti−tnf-iranti−tnf-naïveanti−tnf-naïve secukinumab secukinumab secukinumab lda remission 19.0 18.4 10.0 24.0 19.7 15.8 38.9 32.1 35.4 36.7 28.6 13.2 0 12.0 16.4 3.5 22.2 14.3 23.1 14.3 0 10 20 30 40 50 60 70 80 150 mg (n = 38) placebo (n = 30) stneitap fo noitropor p 300 mg (n = 75) 150 mg (n = 61) placebo (n = 57) 150 mg (n = 49) 150 mg (n = 28) 300 mg (n = 18) 300 mg (n = 65) 300 mg (n = 21) week 16 week 104 ≤2 years >2 years ≤2 years >2 years secukinumabsecukinumabsecukinumab lda remission data were reported using mutually exclusive categories at group level and as observed analysis. lda: 1.9< pasdas score <3.2; remission: pasdas score ≤1.9. secukinumab 300 and 150 mg data are reported (approved doses). n, number of patients in the treatment group with evaluation ir, intolerance or inadequate response; lda, low disease activity; pasdas, psoriatic arthritis disease activity score; tnf, tumor necrosis factor figure 6. (a) pasdas remission and lda and patient-reported outcomes; (b) pasdas remission and lda and work productivity haq-di -1.0 -0.8 -0.6 -0.4 -0.2 0.0 n = 69 n = 12 8 n = 53 n = 31 n = 13 n = 95 n = 79 n = 47 * * * * * -4 0 4 8 12 16 facit-fatigue n = 69 n = 12 7 n = 53 n = 31 n = 13 n = 95 n = 80 n = 46 * * * † * -12 -8 -4 0 psa qol n = 69 n = 12 7 n = 53 n = 31 n = 13 n = 94 n = 79 n = 47 * * * * * week 16 week 104 -12 -8 -4 0 dlqi n = 61 n = 11 6 n = 51 n = 29 n = 10 n = 84 n = 73 n = 45 * * * ‡ § * week 16 week 104l s m ea n ch an ge ± s e ls m ea n ch an ge ± s e ls m ea n ch an ge ± s e ls m ea n ch an ge ± s e hda remissionmoda lda -35 -30 -25 -20 -15 -10 -5 0 5 10 n = 2 8 n = 63 n = 35 n = 16 n = 3 n = 42 n = 40 n = 26 * week 16 week 104 overall work impairment due to health * § -20 -15 -10 -5 0 5 10 n = 30 n = 6 7 n = 35 n = 17 n = 45 n = 45 n = 28 week 16 week 104 work time missed due to health 4.4 0.14 -35 -30 -25 -20 -15 -10 -5 0 5 10 n = 28 n = 46 n = 36 n = 18 n = 3 n = 44 n = 43 n = 27 week 16 week 104 impairment while working due to health * * ‡ § † hda remissionmoda lda ls m ea n ch an ge ± s e n = 3 data from mmrm analysis are pooled across treatment arms. *p < 0.0001; †p < 0.001; §p < 0.01 and ‡p < 0.05 versus hda. n, number of patients with measurements at baseline and post-baseline visits. dlqi, dermatology life quality index; facit-fatigue, functional assessment of chronic illness therapy-fatigue; haq-di, health assessment questionnaire disability index; hda, high disease activity; lda, low disease activity; ls, least squares; mmrm, mixedeffect model repeated measure; moda, moderate disease activity; pasdas, psoriatic arthritis disease activity score; psa, psoriatic arthritis; psa qol, psa-specific quality of life; qol, quality of life; se, standard error • the proportion of patients achieving pasdas remission increased from week 16 to week 104 with both secukinumab 300 mg and secukinumab 150 mg (figure 2) figure 2. pasdas remission and lda through week 104 22.9 19.2 13.8 36.1 35.1 15.6 15.2 2.3 22.9 14.3 0 10 20 30 40 50 60 70 300 mg (n = 96) 150 mg (n = 99) placebo (n = 87) 300 mg (n = 83) 150 mg (n = 77) stneitap fo noitropor p secukinumab secukinumab week 16 week 104 lda remission data were reported using mutually exclusive categories at group level and as observed analysis. lda: 1.9< pasdas score <3.2; remission: pasdas score ≤1.9. secukinumab 300 and 150 mg data are reported (approved doses). n, number of patients in the treatment group with evaluation. lda, low disease activity; pasdas, psoriatic arthritis disease activity score • the majority of patients receiving secukinumab sustained or improved their pasdas disease activity state at week 16 to week 52 and week 104 (figure 3) figure 3. shift analysis on pasdas disease activity states from week 16 to 52 or 104 24.1 5.3 0.0 58.6 56.1 25.0 0.0 10.3 32.5 50.0 35.5 6.9 6.1 25.0 64.5 0 20 40 60 80 100 lda (n = 52) moda (n = 114) hda (n = 58) remission (n = 31) week 16 to week 52 (n = 255) pasdas states at week 16 19.6 1.0 4.2 0.0 54.9 49.5 22.9 10.0 15.7 39.0 41.7 40.0 9.8 10.5 31.3 50.0 0 20 40 60 80 100 remission (n = 30) lda (n = 48) moda (n = 105) hda (n = 51) p ro po rt io n of p at ie nt s at w ee k 10 4 p ro po rt io n of p at ie nt s at w ee k 52 week 16 to week 104 (n = 234) pasdas states at week 16 hda remissionmoda lda data pooled across treatment arms (secukinumab 300 and 150 mg). data were reported using mutually exclusive categories at group level and as observed analysis. hda: pasdas score ≥5.4; moda: 3.2≤ pasdas score <5.4; lda: 1.9< pasdas score <3.2; remission: pasdas score ≤1.9. n, number of patients in each pasdas state at week 16; n, total number of patients with non-missing pasdas score data at weeks 16 and 52/104 hda, high disease activity; lda, low disease activity; moda, moderate disease activity; pasdas, psoriatic arthritis disease activity score • there were generally greater improvements in physician global visual analog scale (vas), patient global vas, swollen joint count, and tender joint count in patients receiving secukinumab achieving pasdas remission than lda (figure 4a) • severity of enthesitis and dactylitis was low in patients receiving secukinumab who achieved either pasdas remission or lda (figure 4b) – greater improvements in sf-36 pcs were observed in patients achieving pasdas remission than lda a a a b b b secukinumab achievement of psoriatic arthritis disease activity score (pasdas)-related remission: 2-year results from a phase 3 study lc coates1, dd gladman2, p nash3, o fitzgerald4, a kavanaugh5, l rasouliyan6, l pricop7, k ding7, c gaillez8, on behalf of the future 2 study group 1nuffield department of orthopaedics, rheumatology and musculoskeletal sciences, university of oxford, oxford, uk; 2toronto western hospital, toronto, on, canada; 3university of queensland, brisbane, australia; 4st vincent’s university hospital, dublin, ireland; 5uc san diego school of medicine, la jolla, ca, usa; 6rti health solutions, barcelona, spain; 7novartis pharmaceuticals corporation, east hanover, nj, usa; 8novartis pharma ag, basel, switzerland summary and conclusions • a high proportion of secukinumab-treated patients achieved pasdas remission or lda at week 16 vs placebo, with sustained pasdas through week 104 – in the overall population, in anti–tnf-naïve patients and irrespective of time since first psa diagnosis (≤2 years vs >2 years) • pasdas remission/lda was associated with significantly greater improvement in health-related quality of life, haq-di, fatigue, and work productivity • pasdas remission and lda represent important states of disease activity in psa with meaningful benefit on life impact from the patient perspective download document at the following url: http://novartis.medicalcongressposters.com/default.aspx?doc=11d0f and via text message (sms) text: q11d0f to: 8nova (86682) us only +18324604729 north, central and south americas; caribbean; china +447860024038 uk, europe & russia +46737494608 sweden, europe scan to download a reprint of this poster acknowledgements the authors thank the patients and their families and all investigators and their staff for participation in the study. oxford pharmagenesis, inc., newtown, pa, usa, provided assistance with layout and printing the poster; this support was funded by novartis pharmaceuticals corporation, east hanover, nj. the authors had full control of the contents of this poster. this research was funded by novartis pharma ag, basel, switzerland. poster presented at: 13th annual winter clinical dermatology conference, maui, hi, usa; january 12–17, 2018. reprinted from the 2017 acr/arhp annual meeting held november 3‒8, 2017. the american college of rheumatology does not guarantee, warrant, or endorse any commercial products or services. reprinted by novartis pharmaceuticals corporation. references 1. helliwell ps and kavanaugh a. arth care res. 2014;66:749-56. 2. helliwell ps, et al. ann rheum dis. 2017;pii: annrheumdis-2016-211010. 3. coates lc, et al. ann rheum dis. 2017;76:1688–92. 4. langley rg, et al. n engl j med. 2014;371:326–38. 5. mcinnes ib, et al. rheumatology (oxford). 2017;56(11):1993–2003. 6. mcinnes ib, et al. lancet. 2015;386:1137–46. disclosures l coates: grant/research support from abbvie, janssen; consultant for abbvie, bms, celgene, pfizer, ucb, msd, boehringer ingelheim, novartis, lilly, janssen. dd gladman: grants and/or personal fees from amgen, abbvie, bms, celgene, eli lilly, janssen, novartis, pfizer, ucb. p nash: research grants and honoraria from novartis, abbvie, roche, pfizer, bms, janssen, celgene. o fitzgerald: consultant for bristol-myers squibb, roche, abbott laboratories, pfizer inc, ucb pharma ltd; a kavanaugh: consultant for novartis. l rasouliyan: consultant for novartis through employment at rti health solutions. l pricop, k ding, and c gaillez: shareholders and employees of novartis. skin july 2021 1127 proof returned skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 353 original research treatment of pityriasis rubra pilaris with daily low-dose methotrexate: a retrospective cohort study lauren g. yi, md1, benjamin a. tran, md1, r. hal flowers, md1, kenneth e. greer, md1, darren j. guffey, md1 1university of virginia health system, department of dermatology, charlottesville, va pityriasis rubra pilaris (prp) is a rare papulosquamous disorder. presentation classically features hyperkeratotic follicular papules, scaly salmon-pink plaques, palmoplantar hyperkeratosis, and islands of skin-sparing (“nappes claires”).1,2 treatment is notoriously difficult and no highquality randomized controlled trials exist addressing effectiveness of therapeutic options, which include topical and systemic corticosteroids, phototherapy, retinoids, immunomodulators, and biologics.3-5 up to 80% of patients undergo spontaneous resolution within three years of onset, complicating assessment of treatment effectiveness.1 systematic reviews and case series support methotrexate (mtx) as an effective treatment for prp.3,6-8 potential mechanisms of mtx in treating prp include anti-proliferative and anti-inflammatory effects via reduction of proabstract background: pityriasis rubra pilaris (prp) is a rare disease that can be refractory to many treatments, including corticosteroids, immunomodulatory drugs, and biologics. available literature has primarily described the use of weekly dosing of methotrexate, but there is limited data investigating the effectiveness of daily low-dose methotrexate in prp treatment. methods: a retrospective cohort study was conducted from september 2010 to december 2019 to determine the effectiveness of daily low-dose methotrexate in treating prp. results: the average duration of follow-up was 13.5 months. 14 patients were treated with oral daily low-dose methotrexate. 13 patients (92.9%) showed improvement on oral daily low-dose methotrexate. mean time to clinical response was 5.9 weeks. in seven patients (50%), complete response on methotrexate monotherapy occurred within an average of 11.9 months. 12 patients (85.7%) developed asymptomatic elevations in liver enzymes (alt and ast) that resolved in most patients (66.7%) after dose reduction. conclusions: in this study, daily low-dose methotrexate was an effective treatment of prp and may be considered in patients unresponsive to weekly dosing. due to the high incidence of elevated liver enzymes, the authors recommend frequent lab monitoring and screening for risk factors. further studies are warranted to elucidate the efficacy of daily low-dose methotrexate in the management of prp. introduction skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 354 inflammatory cytokines il-1, il-2, ifn-γ, and tnf-α and increasing anti-inflammatory cytokines il-4 and il-10.8,9 available literature has primarily investigated weekly dosing of mtx.2 however, one case series notably observed excellent response rates in patients treated with daily dosing when compared with weekly mtx.2 while daily dosing is speculated to increase risk of toxicity, one author (kg) has effectively and safely used daily low-dose mtx in treating prp for over four decades.2 he has noted success in many cases that were unresponsive to several other treatments, including weekly mtx. thus, we seek to report our experience with the efficacy of daily low-dose mtx in treatment of prp. the university of virginia institutional review board approved this retrospective cohort study. patients diagnosed with and treated for prp were identified from the electronic medical record from september 2010 to december 2019. initial search returned 28 patients diagnosed with prp based on clinical or histopathologic features. patients without follow-up after their initial presentation in clinic or those on weekly mtx were excluded. in all, fourteen patients treated with low-dose daily mtx were included in the analysis. four patients were diagnosed with prp based on biopsy while the rest were diagnosed clinically. two of these patients had biopsies at outside hospitals suggestive of parapsoriasis and psoriasis respectively, while five had nonspecific biopsy results. patients were most commonly initiated on oral mtx at 2.5 mg six days weekly (table 1). table 1. mtx dosing regimens (n) dosage 2.5 mg for 6 days/wk (9) 2.5 mg for 7 days/week (3) 2.5 mg for 5 days/week (1) 2.5 mg for 6 days/wk + 5 mg on 7th day (1) dosing was adjusted based on individual clinical course. patients that cleared on mtx were tapered off by reducing the weekly cumulative dose by 2.5 mg each month. patient demographics and treatment data, including symptoms, prior treatments, mtx dosage, improvement timeline, and adverse effects were collected. treatment response categories included no response (nr), partial response (pr), and complete response (cr) based on a global assessment. pr was defined as any reduction in involved body surface area whereas cr was defined as the complete clearance of the rash. therapeutic response time was recorded as the time from mtx initiation to first observed improvement in involved bsa, erythema, or pruritus. table 2 depicts the patient cohort demographics. the average age of patients was 63 years (sd = 12.5). table 3 summarizes each patient in the study. the majority (78.6%) of patients’ rashes had failed multiple treatments including topical and systemic corticosteroids, cyclosporine, acitretin, adalimumab, apremilast, ustekinumab, and weekly methotrexate. treatment failure was defined as either the absence of clinical improvement on a therapy or when an adverse reaction to the medication occurred. daily mtx treatment showed a 92.9% response rate with a pr occurring in 42.9% and cr occurring in 50% of patients. mean methods results skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 355 table 2. patient demographics characteristics (n=14) mean age 63 males/females 12/2 previous treatments, n (%) topical corticosteroids oral steroids cyclosporine acitretin adalimumab apremilast ustekinumab weekly methotrexate 7 (50%) 7 (50%) 1 (7.1%) 1 (7.1%) 2 (14.2%) 1 (7.1%) 2 (14.2%) 3 (21.4%) previous diagnoses, n (%) psoriasis para-psoriasis allergic contact dermatitis 3 (21.4%) 1 (7.1%) 2 (14.2%) comorbidities predisposing to transaminitis, n (%) diabetes mellitus hyperlipidemia current or previous alcohol use baseline elevated transaminases 3 (21.4%) 2 (14.2%) 2 (14.2%) 3 (21.4%) mean duration of follow-up 13.5 months rate of loss to follow-up 14.3% (2/14) time to any clinical response was 5.9 weeks (sd = 3.2) and mean time to cr was 11.9 months (sd = 5.7). as of december 2019, to the authors’ knowledge, all patients that achieved cr remain disease-free. a complete blood count and liver enzymes (alt and ast) were checked every few months at follow-up visits while patients were on mtx. elevations in alt and/or ast were the most common adverse effect, occurring in 12 (85.7%) patients. none of these patients had previously documented hepatic or renal disease. eleven of these patients had available alt and ast levels in our medical record system and most (72.7%) were less than three times the upper limit of normal. the mean alt value in these patients (n=11) was 128.6 units/l (sd = 58.9) while the average ast was 76.9 units/l (sd = 48.1). all patients were asymptomatic and none required hospital admission. two patients had persistently elevated liver enzymes between four and five times the upper limit of normal that resolved within four weeks of dose reduction. one patient discontinued mtx and switched to acitretin due to persistent mild elevations in alt and ast and inability to afford frequent lab draws. 35.7% of patients experienced other side effects including mucositis, dizziness, stinging sensation of skin, and decrease in hemoglobin. two patients (7 and 13) transitioned either to ixekizumab or acitretin due to lack of efficacy and both achieved cr on the subsequent agent. patient 4 responded to daily low-dose mtx after failing adalimumab and ustekinumab. three patients (1, 6, and 13) were previously on weekly mtx (25 mg, 15 mg, and 25 mg respectively) before starting daily dosing. patient 1 achieved further improvement on daily low-dose mtx while patient 6 achieved cr on daily dosing. patient 8 achieved cr once ixekizumab was added to mtx. there is a lack of high-quality evidence guiding treatment of prp. one treatment algorithm recommends topical corticosteroids and systemic retinoids as first-line, mtx as second-line, and biologics as third-line.5 however, the optimal dosing, duration of therapy, and route of mtx for treating prp are not established. knowles and colleagues treated six men with refractory prp with intermittent intravenous, intermittent intramuscular, intermittent weekly oral, and daily oral mtx.2 they found that oral mtx, alternating between 5 mg and 2.5 mg daily, required fewer total weeks to achieve remission and demonstrated a lower discussion skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 356 table 3. summary of patients patient age (y) gender mtx dose outcome reported adverse effects 1 63 f 2.5 mg every day pr mucositis 2 64 m 2.5 mg daily for 6 days/week cr elevation in liver enzymes 3 43 m 2.5 mg daily for 6 days/week nr; switched to acitretin elevation in liver enzymes 4 68 m 2.5 mg daily for 6 days/week cr elevation in liver enzymes 5 72 m 2.5 mg daily for 6 days/week pr; lost to follow-up elevation in liver enzymes, burning sensation of skin 6 81 m 2.5 mg every day cr elevation in liver enzymes 7 67 m 2.5 mg daily for 6 days/week pr; switched to acitretin elevation in liver enzymes 8 68 m 2.5 mg daily for 5 days/week pr; added on ixekizumab elevation in liver enzymes, decrease in hemoglobin 9 71 m 2.5 mg daily for 6 days/week pr; lost to follow-up none 10 43 m 2.5 mg daily for 6 days/week cr elevation in liver enzymes 11 67 f 2.5 mg daily for 6 days/week cr elevation in liver enzymes 12 77 m 2.5 mg daily for 6 days/week cr elevation in liver enzymes, decrease in hemoglobin 13 45 m 2.5 mg daily for 6 days/week + 5 mg on 7th day of week pr; switched to ixekizumab elevation in liver enzymes, dizziness 14 50 m 2.5 mg every day cr elevation in liver enzymes relapse rate compared with intermittent intravenous or intramuscular mtx. furthermore, two patients who did not respond to either weekly oral, intramuscular, or intravenous mtx subsequently responded to daily oral low-dose mtx. in this study, daily oral low-dose mtx was effective with 92.9% of patients responding and 50% achieving cr, consistent with the 90.9% overall response rate and 40.9% complete clearance rate reported in a recent review of 44 patients treated with oral or subcutaneous mtx.8 the mean times to any improvement (5.9 weeks) and to cr (11.9 months) were consistent with reported response times of 3-12 weeks.8-12 duration of therapy often lasted several months (range 112 months).8 because up to 80% of patients with prp undergo spontaneous remission, it is possible that the natural history of prp confounds these results.1 elevated liver enzymes were notably very common in this cohort, occurring in 85.7% of patients. all patients were asymptomatic. most patients’ alt and ast levels were less than three times the upper limit of normal. elevations in liver enzymes resolved in 66.7% of patients within two to four weeks after dose reduction and only one patient discontinued therapy due to persistently elevated liver enzymes. predisposing risk factors for mtx-induced hepatotoxicity including alcohol use, diabetes mellitus, hyperlipidemia, and baseline elevated liver skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 357 enzymes were seen in 50% of patients.13 because daily folic acid supplementation may decrease the efficacy of mtx, 78.6% of patients were not on folic acid, which can increase risk of hepatotoxicity.13,14 the rates of elevated liver enzymes with mtx in this study were higher than that reported in the literature. one randomized controlled trial in patients with generalized plaque psoriasis found that 44% of patients experienced liver enzyme elevation on daily mtx.15 in contrast, 33% of patients on weekly mtx experienced liver enzyme elevation.15 however, daily administration resulted in less nausea, vomiting, and fatigue.15 the rates of elevated liver enzymes in patients with prp on mtx may be underreported in the literature, which consists mainly of studies with small sample sizes. furthermore, patients with prp tend to be elderly and may have comorbidities increasing their susceptibility to side effects. the decision to start mtx therapy on patients with prp should be based on the patient’s medical history. for those with few comorbidities predisposing to hepatotoxicity on mtx, the benefits of mtx therapy may outweigh the risks. providers should monitor strictly with routine labs and screen for risk factors before starting mtx. clinicians should consider cost when selecting treatment agents given the typical duration of therapy until remission in prp (11.9 months). cost-effectiveness analyses estimate the annual costs of adalimumab in treating psoriasis to be $23,538, while newer interleukin-17 inhibitors cost between $37,224 (brodalumab) and $64,396 (ixekizumab).16,17 in contrast, mtx 7.5 mg weekly costs only $1,197.16 limitations of this study include small sample size and its retrospective nature. the mean duration of follow-up in this study was only 13.5 months (table 2) and two patients (14.3%) were lost to follow-up. magnitude of bsa improvement and time to achieve cr in this cohort were difficult to objectively measure. inconsistent follow-up intervals may also introduce bias. treatment of prp is challenging. various routes and dosages of mtx can induce remission. in this study, oral daily low-dose mtx was an effective treatment of prp. the markedly lower financial cost and availability of mtx make it a favorable option. furthermore, a trial of daily low-dose mtx may be considered for patients unresponsive to weekly dosing. due to the high incidence of elevated liver enzymes in this cohort, the authors recommend frequent lab monitoring and appropriate screening for hepatotoxicity risk factors. further randomized controlled trials are warranted to elucidate the efficacy of oral daily low-dose mtx in prp management. conflict of interest disclosures: none funding: none corresponding author: lauren yi, md 1221 lee st charlottesville, va 22909 phone: 434-924-5115 fax: 434-244-4504 email: lgy8qu@virginia.edu references: 1. r griffiths wa. pityriasis rubra pilaris. clin exp dermatol. 1980;5(1):105-112. 2. knowles wr, chernosky me. pityriasis rubra pilaris: prolonged treatment with methotrexate. arch dermatol. 1970;102(6):603-612. 3. kromer c, sabat r, celis d, et al. systemic therapies of pityriasis rubra pilaris: a systematic review. j dtsch dermatol ges. 2019;17(3):243259. conclusion skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 358 4. ross na, chung hj, li q, et al. epidemiologic, clinicopathologic, diagnostic, and management challenges of pityriasis rubra pilaris: a case series of 100 patients. jama dermatol. 2016;152(6):670-675. 5. roenneberg s, biedermann t. pityriasis rubra pilaris: algorithms for diagnosis and treatment. j eur acad dermatol venereol. 2018;32(6):889898. 6. alazemi a, balakirski g, alshehhi f, et al. juvenile pityriasis rubra pilaris: successful treatment with methotrexate. clin exp dermatol. 2018;43(1):110-112. 7. gemmeke a, schönlebe j, koch a, et al. pityriasis rubra pilaris—a retrospective single center analysis over eight years. j dtsch dermatol ges. 2010;8(6):439-444. 8. koch l, schöffl c, aberer w, et al. methotrexate treatment for pityriasis rubra pilaris: a case series and literature review. acta derm venereol. 2018;98(5):501-505. 9. brown j, perry ho. pityriasis rubra pilaris: treatment with folic acid antagonists. arch dermatol. 1966;94(5):636-638. 10. parish lc, woo th. pityriasis rubra pilaris in korea: treatment with methotrexate. dermatologica. 1969;139(6):399-403. 11. anderson fe. pityriasis rubra pilaris treated with methotrexate. aust j dermatol. 1966;8(3):183185. 12. chapalain v, beylot-barry m, doutre ms, et al. treatment of pityriasis rubra pilaris: a retrospective study of 14 patients. j dermatol treat. 1999;10(2):113-117. 13. bath rk, brar nk, forouhar fa, et al. a review of methotrexate-associated hepatotoxicity. j dig dis. 2014;15(10):517-524. 14. cline a, jorizzo jl. does daily folic acid supplementation reduce methotrexate efficacy? dermatol online j. 2017;23(11):13030/qt4hf5v2vk. 15. radmanesh m, rafiei b, moosavi z, et al. weekly vs. daily administration of oral methotrexate (mtx) for generalized plaque psoriasis: a randomized controlled clinical trial. int j dermatol. 2011;50(10):1291-1293. 16. beyer v, wolverton se. recent trends in systemic psoriasis treatment costs. arch dermatol. 2010;146(1):46-54. 17. wu j, rastogi s, menges b, et al. comparison of the cost-effectiveness of biologic drugs used for moderate-to-severe psoriasis treatment in the united states. j dermatol treat. 2018;29(8):769774 skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 156 brief article a case of shiitake mushroom dermatitis in a 21-year-old female sheena t. hill, md, mph1, kord s. honda, md1, bethany r. rohr, md1 1department of dermatology, university hospitals cleveland medical center, cleveland, oh shiitake mushroom dermatitis is a phenomenon that was first described in japanese literature in 1977.1 cases have now been reported throughout europe, north america, and south america.2 it is a rare cutaneous reaction caused by consumption of raw or undercooked shiitake mushrooms (lentinula edodes). lentinan, a heat-inactivated β-glucan polysaccharide, is proposed to cause this dermatitis.3 heat alters its structure, which is why this dermatitis is not seen with cooked shiitake mushrooms. to the authors’ knowledge, there have been few cases describing histologic findings of shiitake mushroom dermatitis. here we present a case of shiitake mushroom dermatitis with correlation of histologic findings. a 21-year-old female presented with a fiveday history of an extremely pruritic diffuse rash. she reported no new medications, products, preceding illness, or other notable positive review of systems, but did note cooking with shiitake mushrooms the day before onset of the rash. on physical examination, she had flagellate erythema on the posterior neck, arms, abdomen, bilateral flanks, and lower back, as well as scattered papules and vesicles (figures 1-2). figure 1. shiitake mushroom dermatitis. flagellate erythema of the right flank, where punch biopsy was performed. figure 2. shiitake mushroom dermatitis. flagellate erythema of the neck, shoulders, and upper back. introduction case presentation skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 157 a punch biopsy from the right flank was performed. histopathologic evaluation revealed an interface dermatitis with focal parakeratosis, mild basal layer vacuolization, and a mild superficial perivascular lymphocytic infiltrate (figures 3a and 3b). she noted improvement at twoweek phone follow-up with use of triamcinolone 0.1% cream and shiitake mushroom avoidance. figure 3. (a) punch biopsy. superficial perivascular lymphocytic infiltrate with mild basal layer vacuolization (h&e, 40x). (b) punch biopsy. higher magnification showing parakeratosis in an area of possible erosion with mild vacuolar alteration of basal keratinocytes and a superficial perivascular lymphocytic infiltrate (h&e, 100x). the exact pathophysiology of shiitake mushroom dermatitis is not well understood. it is thought that lentinan causes this dermatitis by a toxic or hypersensitivity reaction through activation of interleukin-1, thereby causing vasodilation and a rash.3,4 for those who favor a toxic mechanism, it is proposed that lentinan induces vasodilation and subsequent inflammation through interleukin.5,6,8,9 for those who favor a hypersensitivity mechanism, it is proposed that lentinan may cause a th1 skew over th2.3 although there have been cases of positive patch testing in shiitake mushroom dermatitis, patch tests are usually negative due to poor antigen penetration.10,11 patch tests are also not consistently positive in delayed food reactions.12 because lentinan is thermolabile – inactivated at temperatures between 130 and 145 degrees celsius due to irreversible molecular structure changes – shiitake mushroom dermatitis is not seen with well-cooked mushrooms.5 the histopathologic findings of flagellate erythema, specifically in shiitake mushroom dermatitis, are non-specific (table 1). in a review of three flagellate erythema cases, histologic findings showed spongiosis and variable interface dermatitis with dermal lymphohistiocytic infiltrate.6,7 eosinophils were prominent in two cases. in other case reports, histologic findings were variable and included hyperkeratosis, parakeratosis, dyskeratosis, spongiosis, and superficial mixed perivascular infiltrate with neutrophils, lymphocytes, and eosinophils.13-15 the clinical differential diagnosis in these cases should include bleomycin-induced flagellate hyperpigmentation, dermatomyositis, adult-onset still disease, and acute contact dermatitis. clinicalt discussion a. b. skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 158 table 1. literature review of histopathologic findings in flagellate erythema case sex age (years) histopathology additional findings exposure treatment chu et al 20137 f 46 superficial and mid-dermal perivascular mixed lymphocytic infiltrate with occasional eosinophils and neutrophils. focal perivascular fibrin deposition. normal alt/ast, cbc with differential (including eosinophils) chinese restaurant dish with reconstituted dried shiitake mushrooms self-resolved after 4 weeks chu et al 20137 m 46 small foci of epidermal spongiosis with lymphocyte exocytosis. superficial and middermal perivascular and interstitial infiltrate of neutrophils, eosinophils, and mononuclear cells. - chinese restaurant dish with shiitake mushrooms self-resolved after 3 weeks corazza et al 20158 m 30 intact epidermis, papillary dermal edema, erythrocyte overflow, superficial and perivascular mononuclear infiltrate without vasculitis or pigment incontinence - ate large amount of raw mushrooms five hours before onset of rash self-resolved after 3 days nakamura 19926 m 25 -- ate salad with raw shiitake mushrooms resolved in 10 days after treatment with antihistamine and topical steroids soo et al 200715 m 58 mild to moderate spongiosis with focal hyperkeratosis, midparakeratosis and minimal lymphocyte exocytosis. mild perivascular lymphohistiocytic inflammatory infiltrate in superficial and mid-dermis. normal cbc (including eosinophils), serum ck chinese restaurant meal the night before antihistamines and topical corticosteroids hanada 199813 m 44 intercellular edema, individual cell death, dermal edema, lymphocytic infiltrate, dilation of capillary vessels negative ana, normal porphyrins (urine, fecal, serum), normal ck, negative patch and photopatch tests 15-20 pieces of shiitake mushrooms daily for last 7 days resolved in 7 days with antihistamines and topical corticosteroids m – male; f-female; alt – alanine transaminase; ast – aspartate transaminase; cbc – complete blood count; ck – creatine kinase presentation differs in that pigmentation or hyperpigmentation is the main cutaneous finding in bleomycin-induced cases. in dermatomyositis, the rash is more inflammatory with persistent erythema and may be accompanied by photodistributed poikiloderma.1 review of systems should include questions about myalgias, dysphagia, dyspnea, arrhythmias, and arthritis.1 in adult-onset still disease, patients may report preceding sore throat, myalgias, or arthralgias, as well as recurrent fevers.1 in shiitake mushroom dermatitis, there are flagellate streaks made up of erythematous papules or vesicles, which may resolve with post-inflammatory skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 159 hyperpigmentation.1 histopathology is not diagnostic and the diagnosis can be made clinically. shiitake mushroom dermatitis typically selfresolves in one to eight weeks with avoidance of mushrooms. patients are advised to thoroughly cook shiitake mushrooms prior to future consumption, which typically prevents recurrence. symptomatic treatments include topical corticosteroids and oral antihistamines. our patient improved with topical corticosteroids and mushroom avoidance. we present this case to highlight the importance of detailed history taking and to describe rarely reported histologic findings of shiitake mushroom dermatitis. conflict of interest disclosures: none funding: none corresponding author: sheena t. hill, md, mph department of dermatology university hospitals cleveland medical center 11100 euclid avenue lakeside 3500 cleveland, oh 44106 phone: 216-844-8200 fax: 216-844-8993 email: sheena.hill@uhhospitals.org references: 1. bolognia jl, schaffer jv, cerroni l, editors. dermatology, 4th edition. china: elsevier; 2018. p. 1129-1130. 2. stephany mp, chung s, handler mz, handler ns, handler ga, schwartz ra. shiitake mushroom dermatitis: a review. am j clin dermatol. 2016 oct; 17(5):485-489. 3. nguyen a, gonzaga m, lim v, adler m, mitkov m, cappel m. clinical features of shiitake dermatitis: a systematic review. int j dermatol. 2017; 56(6):610-616. 4. hanada k, hashimoto i. flagellate mushroom (shiitake) dermatitis and photosensitivity. dermatology 1998; 197(3):255-257. 5. netchiporouk e, pehr k, ben-soshan m, billick rc, sasseville d, singer m. pustular flagellate dermatitis after consumption of shiitake mushrooms. jaad case rep. 2015 may; 1(3):117-119. 6. nakamura t. shiitake (lentinus edodes) dermatitis. contact dermatitis 1992 aug; 27(2):65-70. 7. chu ey, anand d, dawn a, elenitsas r, adler dj. shiitake dermatitis. a report of 3 cases and review of the literature. cutis 2013;91:287-290. 8. corazza m, zauli s, ricci m, borghi a, pedriali m, mantovani l, virgili a. shiitake dermatitis: toxic or allergic reaction? j eur acad dermatol venereol. 2015 jul; 29(7):1449-1451. 9. tan q, tan c. log-grown shiitake is perhaps the real cause for shiitake dermatitis. j eur acad dermatol venereol. 2016 jan; 30(1):197-198. 10. ching d, wood ba, tiwari s, chan j, harvey nt. histological features of flagellate erythema. am j dermatopathol. 2019 jun; 41(6):410-421. 11. kopp t, mastan p, mothes n, tzaneva s, stingl g, tanew a. systemic allergic contact dermatitis due to consumption of raw shiitake mushroom. clin exp dermatol. 2009;34:e910-913. 12. sutas y, kekki om, isolauri e. late onset reactions to oral food challenge are linked to low serum interleukin-10 concentrations in patients with atopic dermatitis and food allergy. clin exp allergy. 2000;30:1121-1128. 13. hanada k, hashimoto i. flagellate mushroom (shiitake) dermatitis and photosensitivity. dermatology. 1998;197: 255-257. 14. lippert u, martin v, schwertfeger c, et al. shiitake dermatitis. br j dermatol. 2003;148: 178-179. 15. soo jk, pearson ic, misch kj. a case of flagellation. clin exp dermatol. 2007;32: 339340. conclusion mailto:sheena.hill@uhhospitals.org skin january 2019 volume 3 issue 1 copyright 2018 the national society for cutaneous medicine 116 compelling comments nobel niels jacob e. benavidez, bs1 1university of texas medical branch school of medicine, galveston, tx niels ryberg finsen's (1860–1904) realization of light's therapeutic application, particularly for lupus vulgaris, earned him the 1903 nobel prize in medicine.1 presently, phototherapy is a treatment staple for various cutaneous disorders, but its inspiration and elucidation are resultant of the faroese physician's struggle with niemann-pick disease.1 bathing in the sun, finsen experienced reduced fatigue from his disease, inspiring his life's work.1 finsen developed a lamp with a quartz lens and an artificial light source generated by electric carbon arcs. this phototherapeutic apparatus, known as the finsen light, helped niels become dermatology's nobel laureate.1 niels’s disease manifested in 1883, but with the finsen light and persistent effort, he developed a treatment for smallpox using red-light, and by taking advantage of ultraviolet radiation's bactericidal effect, a treatment for the cutaneous manifestation of tuberculosis, lupus vulgaris.3 in 1893, finsen observed that exposure to red-light prevented the suppurative pustulation of smallpox and reduced scar pigmentation if treated before the fifth day of disease.2 explanation of this phenomenon is rooted in light's behavior; a red lens permits red-shifted light's shallow dermal penetration while refracting blue-shifted light.2 in 1895, drastic improvements were observed within only four days in a lupus vulgaris patient treated with concentrated light rays. with this, dermatology welcomed finsen's phototherapy.3 finsen's work garnered the attention of the global medical community.1 in 1896, with support from copenhagen's mayor and generous donors, the finsen institute was established with niels as its first director.1 within a few years, skin january 2019 volume 3 issue 1 copyright 2018 the national society for cutaneous medicine 117 finsen institutes were erected across europe and north america.1 niels endeavored to relieve his disease, and although phototherapy endures, he could not escape time's pursuit. though wheelchairbound and unable to accept his prize personally, his phototherapy and nobelworthy efforts paved a new avenue of treatment for dermatology. as phototherapy’s spectrum of cutaneous applications expands, finsen's legacy thrives. conflict of interest disclosures: none. funding: none. corresponding author: jacob e benavidez, bs the university of texas medical branch galveston, tx jacobbenavidez7@gmail.com references: 1. grzybowski a, pietrzak k. from patient to discoverer—niels ryberg finsen (1860–1904)—the founder of phototherapy in dermatology. clinics in dermatology. 2012;30(4):451-455. doi:10.1016/j.clindermatol.2011.11.01 9. 2. finsen nr. the red light treatment of small-pox. bmj. 1895;2(1823):14121414. doi:10.1136/bmj.2.1823.1412-a. 3. moller ki, kongshoj b, philipsen pa, thomsen vo, wulf hc. how finsen's light cured lupus vulgaris. photodermatology, photoimmunology and photomedicine. 2005;21(3):118124. doi:10.1111/j.16000781.2005.00159.x. skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 364 in-depth reviews psoriasis and obesity: a review of the current literature jeremy n. orloff ba1, joshua r. kaminetsky ba1,2, mina aziz ba1 1department of dermatology, icahn school of medicine at mount sinai, new york, ny 2albert einstein college of medicine, bronx, ny psoriasis is a chronic inflammatory skin disorder characterized by hyperproliferation and abnormal maturation of keratinocytes in the dermis. it affects approximately 2-3% of the world population and typically manifests as erythematous plaques and patches with a silver scale, most commonly on the knees, elbows, scalp, lower back, and extensor surfaces of the limbs.1 disease severity can range from mild skin involvement to severe widespread disease accompanied by notable physical disfigurement and psychosocial ramifications for the afflicted.2 obesity is defined as a body mass index (bmi) greater than 30 and is typically the result of a disturbance in the balance between energy intake, expenditure, and storage. in addition to its numerous wellestablished comorbidities, obesity is also associated with psoriasis, and the complex relationship between psoriasis and obesity has been an area of focus for many researchers and clinicians over the last several decades. this attention is certainly warranted, as the clinical implications of treating patients with psoriatic disease and comorbid obesity are numerous and significant. the association between these two diseases was first described in a large swedish study in 1986 in which 159,200 patients were followed over 10 years3, and the correlative relationship has been identified and continually corroborated in many studies since.4,5,6,7,8 an analysis of 40,000 patients found that obesity occurs significantly more often in patients with psoriasis compared to introduction obesity is currently considered a low-grade chronic inflammatory condition that has welldocumented associations with heart disease, hypertension, diabetes mellitus, and metabolic syndrome. in addition to these conditions, there is growing evidence that the inflammatory cytokines produced in obesity may play contributory roles in other inflammatory phenomena. notably, numerous studies over the last several decades have shed light on the genetic, mechanistic, and epidemiologic links between obesity and psoriasis, with implications for the treatment of these patients. this article reviews the current literature regarding the relationship of obesity and psoriasis, with exploration of their common mechanistic etiology and the necessary considerations in the management, both pharmacological and otherwise, of this patient population. abstract skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 365 control subjects.4 similarly, a case-control study of 560 patients noted an increased frequency of psoriasis in overweight (bmi 2629) and obese (bmi ≥30) patients, with respective odds ratios (or) of 1.6 and 1.9.5 a large uk registry-based analysis of 127,706 patients with mild psoriasis and 3,854 with severe psoriasis requiring systemic treatment or phototherapy found that those with severe disease had a higher odds ratio (1.8) of being obese than those patients in the non-severe group (or 1.3)6. in another study 13% of morbidly obese patients reported psoriasis, compared to 11% of obese and 5% of non-obese patients.9 a recent article demonstrated a strong positive correlation between psoriasis area severity index (pasi) score and waist-to-height ratio.10 these studies convincingly depict a positive correlation between psoriasis and obesity. given that over 1 in 3 u.s. adults are obese11 and that the proportion is rapidly rising, the relationship between obesity and psoriasis is of particular importance to dermatologists, along with clinicians in other fields who will likely see an increase in symptoms and diseases secondary to the far-reaching effects of obesity. not only will the number of obese patients with psoriasis increase, but as highlighted ahead in this article, the management of those cases will be notably more complex as well. it is therefore important that dermatologists be aware of the ramifications of obesity on a patient’s psoriasis and become familiar with the adjustments necessary to properly manage their disease. as evidenced above, the association between obesity and psoriasis has been welldocumented in the literature. however, exactly how the two diseases relate to one another and specifically the direction of causality are points of less unanimous agreement. it has been classically proposed that psoriasis is a risk factor for subsequent weight gain.12 mechanisms by which this occurs emphasize the frequent selfperceived cosmetic disfigurement caused by psoriasis, resulting in social isolation, unhealthy nutrition habits, depression, and alcohol consumption. one study found that psoriasis patients consume more fat, saturated fat, and alcohol.13 additionally, the negative psychological impact of psoriasis can reduce physical activity, especially if the patient also suffers from concomitant psoriatic arthritis. there are several reports that support the directionality of psoriasis prompting weight gain. herron et al surveyed 557 patients with psoriasis and asked them to recall their weight at 18, before the onset of their skin disease. they were also instructed to evaluate their current size, after the onset of psoriasis. it was noted that self-reported obesity at 18 years old, before the onset of psoriasis, did not place patients at risk of developing the skin disease. however, patients who did have psoriasis were noted to weigh more, implying that psoriasis preceded obesity in these patients.9 similarly, a comparison between 200 patients with psoriasis diagnosed within the previous 12 months and matched controls showed no statistical difference in bmi. in fact, obesity rates were slightly higher in the control group compared to the psoriasis group.14 this supports the finding that obesity occurs at some point after the manifestation of psoriasis. on the other hand, there is evidence that the direction of causality is opposite of that proposed above. a large prospective study of psoriasis & obesity skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 366 78,626 women demonstrated that weight gain increased risk for subsequent development of psoriasis. moreover incidence rates were linearly correlated with bmi, with morbidly obese (bmi > 35) patients having greatest relative risk of psoriasis.15 similar findings were reported in a recent prospective norwegian study, demonstrating increased relative risk of psoriasis in heavier patients compared to normal controls.16 in truth, the causality is likely bidirectional and there are elements of all the above arguments that underlie the relationship between the two conditions. moreover, recent investigations into the mechanistic underpinnings of these diseases suggest a shared chronic dysregulated inflammatory state that promotes and perpetuates both conditions. recent research has shed light on the pathophysiologic nature of obesity, psoriasis, and the relationship between the two. it is now known that in addition to its role in metabolism and energy storage, adipose tissue serves as an endocrine organ that produces a wide variety of mediators and signaling molecules for inflammation, immunity, and metabolic regulation. this role may underlie the low-grade inflammatory state that characterizes obesity through the production of pro-inflammatory cytokines such as il-6, c-reactive protein, leptin, resistin and especially tumor necrosis factoralpha (tnf-α).12 tnf-α is a cytokine involved in the regulation and activation of the immune system. its proinflammatory properties assist in the recruitment and stimulation of numerous immune cells throughout the body, inhibiting detrimental processes such as viral replication and tumorigenesis. however, dysregulation of this inflammation has been implicated in a variety of conditions, including alzheimer’s disease, depression, inflammatory bowel disease, and notably psoriasis. while psoriasis’ mechanism has yet to be fully understood, it is strongly believed that it is a t-lymphocyte— specifically th1, th17, and th22—driven process. tnf-α is a prominent cytokine utilized by these cell populations in cellular signaling; accordingly, patients suffering from psoriasis have demonstrated elevated levels of tnf-α in both blood and lesional skin.17 tnf-α expression is also upregulated in obesity, produced largely by the macrophages of stromal and vascular adipose tissue. laboratory studies have found elevated levels of tnf-α mrna in obese rodents.18 biopsies of human tissue have likewise demonstrated increased tnfα mrna in patients with increased body fat19, and cytokine levels have been shown to decrease with weight loss.20 thus, adiposity may contribute to increased levels of tnf-α, which are in turn involved in psoriasis pathophysiology. further intertwining obesity and psoriasis is the satiety hormone leptin. released from adipocytes when sufficient caloric intake has been achieved, this hormone acts to regulate energy balance by sending satiety signals to the hypothalamus. in addition to its metabolic properties, it has also been shown to have immunomodulatory effects as well. mouse models have demonstrated that leptin can bind directly to t-cells, stimulating production of il-2 and interferon-gamma.21 since leptin is a molecule largely released from adipocytes, it follows that it is increased in obese patients and can accordingly have a more potent immune-activating effect on tcells and cytokine production in these mechanistic links skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 367 patients. moreover, tnf-α has been shown to induce rapid release of leptin from adipocytes.22 thus a cyclic interaction may be at play: obese patients, owing to their larger stores of adipose tissue, produce higher levels of leptin. this leptin load stimulates t-cells and promotes production of inflammatory cytokines, including tnf-α. these bioactive signaling molecules not only contribute to and exacerbate psoriasis, but they in turn feedback to adipocytes to release more leptin and perpetuate the cycle. indeed, a metaanalysis of 11 studies has shown leptin levels to be higher in psoriatic patients compared with controls.23 furthermore, it has been shown that leptin levels may be increased in psoriasis independent of bmi24, implying that the hormone may have a pro-inflammatory role in and of itself in psoriasis pathogenesis.25 resistin is another adipokine that may be involved in the mechanistic link between psoriasis and obesity. it is a pro-inflammatory cytokine produced by adipose tissue macrophages and its levels have been associated with inflammatory processes such as atherosclerosis and endothelial dysfunction.26 there is evidence that serum concentrations of resistin are correlated with pasi scores in psoriatic patients and that levels drop when psoriasis is treated27, indicating a possible role in the development of psoriasis. adiponectin is a third cytokine released from adipose cells and has anti-inflammatory properties, including an inhibitory effect on tnf-α, il-6, and interferon-gamma. the levels of this hormone, however, are decreased in obesity28 and are inversely correlated with pasi scores.29 this suggests that adiponectin may normally have a protective effect against psoriasis that cannot be properly mobilized in the setting of obesity. while more research is necessary into the exact mechanistic relationship, the evidence thus far points to a fair degree of overlap, reciprocity, and possible synergy between the inflammatory mediators of psoriasis and obesity. with the relationship between psoriasis and obesity well-evidenced, albeit not fully understood, it is nonetheless important for clinicians managing psoriasis in the obese population to consider the necessary adjustments in treatment. the foremost consideration in treating this patient population is the pharmacokinetic implications of an increased bmi. increased adipose tissue increases the volume of distribution of a drug and can serve as an inert medication reservoir, passively diverting therapeutic agents from their intended active site. to possibly combat this effect, a clinician can consider increasing the dose of a given medication to reach desired efficacy; however, this generates issues in its own right. many of the potent medications for psoriasis are expensive, and increasing the dose may incur unmanageable cost for a patient. additionally, escalating the dose increases risk of drug toxicity and adverse events. moreover, while increasing dose poses risk for adverse events in the general population, special consideration of toxicities is warranted for certain drugs in the obese population, even at normal doses. these will be addressed in later sections. treatment implications skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 368 the option of dose escalation is not even possible for many of the most efficacious medications in the psoriasis armamentarium. many of the biologic agents, now a cornerstone of moderate-to-severe psoriasis management, are administered by prefilled syringes that contain set doses. this makes weight-based incremental dose escalation difficult, if not impossible. lastly, in addition to affected adults, obesity is becoming a major problem among the pediatric population. as of now, few of the potent psoriasis medications are fda approved for treating moderate-to-severe psoriasis in the pediatric age group. only etanercept and ustekinumab are approved, for ages >6 and >12, respectively. amongst these two agents, the latter is preferred owing to it weight-based dosing regimen.30 the following sections will review nonpharmacological interventions, as well as several of the most common psoriasis medication classes and the adjustments to be considered in the setting of obesity. because of the numerous detrimental effects of obesity on psoriasis, management should include weight loss as a foremost goal. weight reduction strategies have a welldocumented beneficial effect on psoriasis, including lifestyle changes, diet control, increased physical activity, and surgical means if more conservative measures fail. the first descriptions of weight loss resulting in improved skin disease come from reports of starving world war ii prisoners.31 a more recent study demonstrated that patients randomized to a low-fat, low-calorie diet for 4 weeks witnessed reductions in total cholesterol, low-density lipoproteins (ldls), triglycerides and improvement of psoriasis compared to those consuming a normal diet.32 this phenomenon was confirmed in a similar randomized controlled trial in which patients were assigned to either a low-energy diet or normal diet.33 the restricted-calorie cohort experienced a subsequent mean weight loss of 15.4 kilograms (kg), reduced pasi scores, and increased quality of life metrics compared to their normal-diet counterparts. another randomized controlled trial by naldi et al showed that patients assigned to a strict dietary and exercise plan achieved a median pasi score reduction of 48% compared to the 25.5% median reduction experienced by the group who received only dietary counseling about the possible benefits of weight loss.34 a metaanalysis of seven randomized controlled trials assessing effectiveness of dietary and lifestyle modifications found that weight loss intervention lowered the average pasi score by 2.5 compared to the non-interventional groups.35 in addition to ameliorating psoriasis disease severity in its own right, evidence suggests that weight loss also potentiates the efficacy of commonly used psoriasis medications. a randomized controlled trial by al-mutairi et al in which patients received either a reducedcalorie or normal diet showed that those with restricted caloric intake and resultant mean weight loss of 12.9 kg had markedly higher response rates to various biologic treatments.36 similarly, naldi et al found that the proportion of patients on systemic medications achieving a 75% reduction in their baseline pasi score (pasi75) decreased with increasing bmi. at 8 weeks, 41.7% patients with bmi < 20 and 29.1% of those with bmi > 30 achieved pasi75. at 16 weeks, those respective percentages weight reduction skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 369 increased to 59% and 42.2%.37 gisondi et al specifically examined weight loss’ effect on cyclosporine and found that even losing 5-10 kg increased favorable response.38 similarly, bardazzi et al examined the effect of weight loss on response to an array of biologic agents and found markedly improved pasi scores in patients who reduced their weight.39 bariatric surgery may present an efficacious option for those who fail more conservative measures. the first report of such an intervention that resulted in psoriatic improvement was a 1977 case of a woman who lost 54 kg after jejunoileal bypass surgery and was able to completely cease medical management with only mild residual disease.40 similarly, three recent case reports discuss complete or near-complete resolution of severe psoriatic disease refractory to medication following roux-en-y gastric bypass, citing maintained disease clearance ranging from several months to more than six years following surgery.41,42,43,44 a recent case report has shown sleeve gastrectomy also demonstrates utility in generating psoriatic improvement following weight loss.45 a review of ten patients who underwent bariatric surgery reported that 70% of the patients remained in remission 6 months following surgery, and 75% were able to discontinue their systemic psoriasis medications.46 in a larger retrospective study, 62% of patients reported improved skin following bariatric surgery, resulting in medication cessation or de-escalation of the potency and classes of treatment agents required for maintenance.47 these findings support the mechanistic hypotheses discussed earlier, as weight loss can therapeutically reduce the inflammation and excess bioactive adipokines that are generated by increased adipose tissue. additionally, postoperative alterations in gastrointestinal hormone secretion may play a role, as psoriasis improvement can even precede any significant postoperative weight loss.48 of the various types of bariatric surgery, it appears roux-en-y gastric bypass (rygb) is most associated with psoriasis improvement45, and it is believed that the gastrointestinal rearrangement following rygb most effectively alters levels of intestinal neuroendocrine hormones, especially glucagon-like peptide-1 (glp-1). the role of glp-1 has been further explored in several studies that reported psoriasis improvement in diabetic patients treated with glp-1 receptor agonists49,50, and more research will further elucidate this phenomenon. this evidence notwithstanding, the effect of weight reduction on psoriasis has not been definitively positive. while a majority of the patients in the above studies did improve with behavioral and/or surgical weight loss interventions, a subset of patients in many of the reports experienced an exacerbation of their skin disease following weight loss.46 in an older trial the majority of patients on restricted-calorie diets had worsened skin disease51, and several case reports since have corroborated that psoriasis can indeed flare following weight loss or gastric bypass surgery.52,53 del giglio et al showed that calorie-restricted patients and free-diet patients relapsed at similar rates following methotrexate-induced disease remission.54 thus, the impact of weight loss on psoriatic disease is clearly complex, and more research is needed. it is worth noting that aside from its effect on psoriasis, weight management is advisable for obese patients in general, as it reduces risk of other morbidity and mortality commonly associated with obesity, including arterial hypertension, skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 370 cardiovascular dysfunction, lipid abnormalities, diabetes, and metabolic syndrome. while weight reduction may carry risk of psoriasis exacerbation, clinicians should nonetheless discuss weight loss with their patients and assess the benefits and risks for their psoriatic disease as well as their overall health and wellbeing. the evidence regarding topical treatment and phototherapy is particularly limited and mostly anecdotal. in a cross-sectional study herron et al found similar efficacy of topical corticosteroids in obese and non-obese patients; however the number of participants and specific data are not revealed. this study also determined that puva achieved similar results in the obese and non-obese populations. in a thorough literature review bremmer et al predicted that ubv psoriasis treatment should not be affected by weight.12 interestingly, however, a recent chinese study found patients suffering from metabolic syndrome, defined as a combination of central obesity, dyslipidemia, glucose intolerance, and hypertension, had poorer response to narrow-band uvb compared to healthy controls.55 in light of this, more investigation is recommended to further explore this psoriasis treatment modality in obese patients. obese patients are more likely to suffer lipid abnormalities at baseline. since acitretin, a retinoid, is known to cause derangements of blood lipid levels, this medication should be used cautiously in the obese population. however, this risk is theoretical, as there is no published literature examining this. like localized treatments, there is scarce literature focused on the use of acitretin for psoriasis in the obese population. for decades methotrexate has been a commonly used systemic medication for moderate-to-severe psoriasis, and it has been demonstrated to be effective in the obese population.9 however, as a known hepatotoxin, methotrexate should be administered more judiciously in heavier patients who may already suffer from fatty liver disease secondary to their obesity.12 berends et al found that among 38 obese psoriasis patients being treated with methotrexate, 4 patients had grade iii or iv roenigk disease on biopsy, whereas none of the 34 non-obese patients had any liver injury.56 in another study, liver biopsies were performed on 24 patients taking methotrexate for psoriasis, 17 of which had non-alcoholic steatotic hepatitis-like patterns of livery injury and 7 of which were healthy. among those 17 patients, 11 were obese, whereas none of the healthy patients were obese.57 rosenberg et al and weinstein et al reported associations of methotrexate with liver fibrosis and fatty changes, respectively, in obese patients taking the medication for psoriasis.58,59 accordingly, clinicians should exercise caution in prescribing methotrexate for these patients, monitor transaminases more closely56, and consider liver biopsy at a lower cumulative dose than the 1.5 grams suggested for the general population.56,59 like methotrexate, the immunosuppressant cyclosporine has known utility in psoriasis treatment, but its adverse effects may be localized treatment acitretin methotrexate cyclosporine skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 371 potentiated in obese patients. specifically, nephrotoxicity is of particular concern. shibata et al demonstrated that even after adjusting for the increased milligram per kilogram dosing for obese patients, obesity is paradoxically correlated with increased serum trough drug levels despite cyclosporine’s lipophilic properties.60 accordingly, maza et al recommend adjusting a patient’s cyclosporine dose according to his/her ideal weight rather than actual weight.61 supporting this recommendation, one study found lower creatinine levels in patients receiving weightindependent dosing of cyclosporine, compared to those whose regimens were increased in proportion to their weight.62 this increased risk of nephrotoxicity is compounded by obesity’s commonly comorbid conditions, such as hypertension and diabetes, that also place the kidneys at risk. additionally, cyclosporine is associated with alterations in lipid metabolism63, and it is unclear to what extent this effect is exacerbated in obese patients who may already suffer from dyslipidemia. careful consideration of risks, monitoring of serum drug levels, frequent blood pressure evaluation, and blood lipid levels are all essential aspects of appropriate management if cyclosporine is to be utilized in obese patients. in the two decades since etanercept was first approved for treatment of rheumatoid arthritis, biologic agents have continually demonstrated efficacy in treating a wide variety of ailments across the vast spectrum of medical specialties. notably, they have been used successfully in patients suffering from moderate-to-severe psoriasis that has not responded to other treatments. their marked potency, general tolerability, and favorable safety profile have made biologics a mainstay of modern-day psoriasis treatment. these desirable traits, however, may not extend fully into the obese population. notably, these potent medications are, for the most part, dispensed in fixed doses, which may fall short of providing the necessary effect in patients of increased bmi. while studies designed specifically to assess this phenomenon are limited, subanalyses conducted from large clinical trials reveal that obese patients who receive a biologic agent restricted to a single fixed dose do not fare as well as those receiving a medication that can be adjusted according to weight. the next paragraphs will review individually several of the most commonly used biologic agents for psoriasis. infliximab is a chimeric monoclonal antibody with a high affinity for tnf-α. of all the biologic agents used for psoriasis, it is currently the only medication that can be dosed on a per kilogram basis, usually 5 milligram per kilogram. accordingly, heavier patients can receive a targeted dose that can be titrated to elicit the best response. indeed, in a subgroup analysis of 1462 patients from 3 clinical trials, reich et al found similar rates of pasi75 among normal weight (77.5%), overweight (78.3%), and obese (74.4%) patients being treated with infliximab.64 similar to infliximab, adalimumab is also a human monoclonal antibody that binds and prevents the activity of solubilized and bound tnf-α. however, adalimumab is dispensed in a 40 milligram (mg) prefilled syringe. a pharmacokinetic study demonstrated that heavier rheumatoid arthritis patients taking adalimumab had increased serum clearance tnf-α inhibitors skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 372 of the drug.65 this pharmacokinetic phenomenon manifests in clinical practice as a reduction in efficacy, evidenced by numerous subanalyses. the believe trial reported that patients weighing more than 95 kg had lower pasi75 rates.66 the reveal trial demonstrated that 63.8% of patients weighing over 100kg achieved pasi75 at week 16 of adalimumab, compared to 74.1% of patients below that weight.67 a 52 week randomized controlled trial reported pasi75 rates of 74%, 80%, 67%, and 62% in the respective weight classes of 40-78 kg, 78-90 kg, 90-105 kg, and 105-204 kg, highlighting a notable inverse relationship between response rate and weight. etanercept is a fixed-dose human soluble tnf receptor fusion protein that binds circulating tnf. data was synthesized from 1187 patients among three clinical trials who received 50 mg of etanercept weekly. pasi75 was achieved by only 25% of the patients above the median weight of 89 kg, compared to the 41% below that weight. in the groups receiving 50 mg twice per week, the respective percentages were 43% and 53%.68 it is interesting to observe that while heavier patients in both dose-frequency cohorts had lower rates of pasi75, the difference between the two weight subgroups in each dose-frequency cohort decreased, suggesting that insufficient response can, at least in part, be mitigated by increasing dose or dose frequency. another study found that among patients with bmi > 40, 15% achieved pasi90, 25% achieved pasi75, 32% achieved pasi50, and 27% achieved less than pasi50. among normal-weight individuals, those respective proportions were 41%, 33%, 17%, and 9%, a distribution notably more skewed toward the more desirable pasi reduction endpoints.69 while the above clinical data support the pharmacokinetic hypothesis that increased adiposity dilutes the concentration and efficacy of tnf-α inhibitors, there are reports providing evidence to the contrary. the champion trial looked at adalimumab compared to methotrexate or placebo. at week 16, pasi75 rates were 85%, 86%, 86%, and 60% for the following four weight classes, respectively: < 68 kg, 68-82 kg, 8292 kg, and > 92 kg.70 the lack of clear inverse relationship between efficacy and weight, except perhaps in the highest weight class, undermines the contention that adalimumab’s fixed dose compromises its effectiveness. there are also studies that demonstrate etanercept’s efficacy is unaffected by weight as well.71,72 moreover, increasing the prescription of doseadjustable medications—such as infliximab—may not fully compensate for a patient’s increased weight. duarte et al conducted a study of 53 patients with moderate-to-severe psoriasis who were treated with 5 mg/kg of infliximab at weeks 0, 2, 6, and every 8 thereafter and found that obesity was associated with a delay in response and lower efficacy.73 evidently obesity’s impact on these medications is nuanced, and further research is encouraged. in addition to the effect of weight on anti-tnfα therapy, it is also important to consider the effect of anti-tnf-α therapy on weight. unfortunately, it appears tnf-α inhibitors may be associated with weight gain. gisondi et al found that patients on 25 mg of etancercept weekly or 5 mg/kg of infliximab gained 2.5 and 1.5 kg, respectively, compared to patients taking methotrexate.74 saraceno et al showed an increase in body weight in 50 psoriasis patients taking etanercept compared to 100 control patients.75 mechanistic hypotheses skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 373 explaining this phenomenon revolve around tnf-α’s previously discussed role in the production and release of leptin, which in turn is a key signaling hormone for satiety.22 iatrogenically reducing the action of tnf-α may downregulate leptin levels, causing hyperphagia and weight gain.75 obese psoriatic patients’ increased adiposity is already associated with numerous detrimental effects, for their skin and other systems of the body; exercising caution is paramount when prescribing a medication that can exacerbate their condition. with that said, tnf-α inhibitors are potent medications in the psoriasis armamentarium, and risks must be weighed against the benefits. the oral phosphodiesterase-4 inhibitor apremilast has shown promise in obese patients. interestingly, despite its downregulation of numerous inflammatory cytokines, including tnf-α, it may not cause the weight gain that has been documented in tnf-α inhibitors. moreover, it may actually cause weight loss in a subset of patients, an additional desirable benefit in the obese population. the esteem 1 and 2 trials reported that the majority of patients taking 30 mg twice daily maintained their weight within 5% of baseline measurements, while a minority lost weight compared to placebo controls.76 additional biologic agents, with targets other than tnf-α, have shown promise in the obese population. ustekinumab is a biologic agent that targets il-12 and il-23, cytokines involved in t-cell activation, and is manufactured in two doses: 45 mg and 90 mg. subanalyses of the phoenix 1 and phoenix 2 trials found correlations between body weight, serum drug concentrations, and efficacy of ustekinumab.77 patients received either 45 mg or 90 mg of ustekinumab every 12 weeks or placebo with crossover to ustekinumab at week 12. in patients weighing < 100 kg, pasi75 response rates were minimally different between the 2 dose groups: 80.8% in the 90-mg subgroup and 76.9% in the 45-mg subgroup. in patients weighing > 100 kg, however, a higher pasi75 rate of 74.2% was observed in the 90-mg subgroup compared to 54.6% of 45-mg patients. these trials also measured serum drug levels and found drug concentrations to be inversely correlated with weight for both dose groups. patients weighing < 100 kg in both the 45-mg group and 90-mg group had similar drug concentrations, correlating well with their similar clinical response. for patients above 100 kg, the 45-mg experienced drug concentrations that fell below the lower limit of quantification in 10-kg increment subpopulations above 100 kg. however, in the 90-mg group, concentrations remained above this threshold, except in the highest weight class of 120-130 kg. thus it appears drug concentrations mirror clinical response. based on these findings, ustekinumab’s higher dose option may serve heavier patients well in achieving desired clinical response. secukinumab, ixekizumab and brodalumab are newer biologic agents that target il-17, a potent inflammatory cytokine with a known role in psoriasis pathogenesis.78 given their relative recency, there is less literature regarding their use in obese patients compared to the older anti-tnf agents, but preliminary analyses show promise. il-17 inhibitors are potent drugs that demonstrate efficacy in both obese and normal-weight patients, though response is usually better in the latter.2 a phase 2 trial of secukinumab reported pasi75 rates of 83% and 73% for patients below 90 kg and above 90 kg, other biologics skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 374 respectively.79 the uncover trials revealed ixekizumab’s efficacy, regardless of body weight.80 the amagine 1 trial demonstrated the efficacy of brodalumab, though pasi75 and pasi90 rates were higher in non-obese patients.81 additionally, il-17 inhibitors have not been shown to cause weight gain, making them desirable in the obese population. this beneficial aspect, combined with their notable efficacy, highlights il-17 inhibitors as an enticing option for obese patients, and continued exploration of their role would be beneficial. the evidence that psoriasis is associated with obesity is convincing, and it is likely that each has a role in promoting and exacerbating the other with genetic, environmental, metabolic, and behavioral factors all contributing. psoriasis is not only more prevalent in the obese population, but is often more stubborn and requires more aggressive treatment and care. this recalcitrance is increasingly complicated by decreased drug efficacy and this population’s heightened susceptibility to adverse effects from the numerous commonly utilized systemic medications. further compounding this complex clinical challenge is the relative scarcity of concrete evidence that makes it difficult to generate definitive treatment recommendations. accordingly, further research is necessary, and clinicians should be aware of the adjustments necessary in treating psoriasis in obese patients. dermatologists should work with each individual patient to develop a treatment plan that works best for him or her, including establishing a trusting therapeutic alliance, working with other clinicians in a multidisciplinary care team, providing nutritional and lifestyle counseling, and prescribing pharmacologic therapy as deemed appropriate. conflict of interest disclosures: none. funding: none. corresponding author: joshua kaminetsky 1425 madison avenue, 15th floor new york, ny 10029 email: jkaminet@mail.einstein.yu.edu references: 1. lebwohl mg, bachelez h, barker j, et al. patient perspective in management of psoriasis: results from the populationbased multinational assessment of psoriasis and psoriatic arthritis survey. j am acad dermatol. 2014 may;70(5):871-81 2. kaushik sb, lebwohl mg. cme part i psoriasis: which therapy for which patient psoriasis comorbidities and preferred 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response to systemic treatment for psoriasis. dermatology. 2008;217:365-373. 38. gisondi p, del giglio m, di francesco v. weight loss improves the response of obese patients with moderate-tosevere chronic plaque psoriasis to lowdose cyclosporine therapy: a randomized, controlled, investigatorblinded clinical trial. am j clin nutr. 2008;88:1242-1247. 39. bardazzi f, balestri r, baldi e, et al. correlation between bmi and pasi in patients affected by moderate to severe psoriasis undergoing biological therapy. dermatol ther. 2010;23(suppl 1):s14–s19. 40. porres jm. jejunoileal bypass and psoriasis. arch dermatol. 1977;113:983. 41. de menezes ettinger je, azaro e, de souza ca, et al. remission of psoriasis after open gastric bypass. obes surg. 2006;16:94-97. 42. higa-sansone g, szomstein s, soto f, et al. psoriasis remission after laparoscopic roux-en-y gastric bypass for morbid obesity. obes surg. 2004;14:1132-1134. skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 377 43. hossler ew, maroon ms, mowad cm. gastric bypass surgery improves psoriasis. j am acad dermatol. 2011;65:198-200. 44. odorici g, conti a. psoriasis improvement after gastric bandage in a patient partial responder to infliximab. dermatol ther. 2018;31(2):e12584. 45. yildiz bd. rapid remission of psoriasis after sleeve gastrectomy. indian j surg. 2016 feb;78(1):60-2. 46. farias mm, achurra p, boza c, et al. psoriasis following bariatric surgery: clinical evolution and impact on quality of life on 10 patients. obes surg. 2012;22(6):877-880. 47. hossler ew, wood gc, still cd. the effect of weight loss surgery on the severity of psoriasis. br j dermatol. 2013;168:660-661. 48. faurschou a, zachariae c, skov l, et al. gastric bypass surgery: improving psoriasis through a glp-1-dependent mechanism? med hypotheses. 2011;77:1098-1101. 49. buysschaert m, tennstedt d, preumont v. improvement of psoriasis during exenatide treatment in a patient with diabetes. diabetes metab. 2012;38:8688. 50. faurschou a, knop fk, thyssen jp, et al. improvement in psoriasis after treatment with the glucagon-like peptide-1 receptor agonist liraglutide. acta diabetol. 2014;51:147-150. 51. zackheim hs, farber em. rapid weight reduction and psoriasis. arch dermatol. 1971;103:136-40. 52. nowlin n, solomon h. weight loss and psoriasis [letter]. arch dermatol. 1976;112:1465. 53. perez-perez l, allegue f, caeiro jl, et al. severe psoriasis, morbid obesity and bariatric surgery. clin exp dermatol. 2009;34:e421-422. 54. del giglio m, gisondi p, tessari g, et al. weight reduction alone may not be sufficient to maintain disease remission in obese patients with psoriasis: a randomized, investigator-blinded study. dermatology. 2012;224:31-37. 55. rui w, xiangyu d, fang x, et al. metabolic syndrome affects narrowband uvb phototherapy response in patients with psoriasis. medicine (baltimore). 2017;96(50). 56. berends ma, snoek j, de jong em, et al. liver injury in long-term methotrexate treatment in psoriasis is relatively infrequent. aliment pharmacol ther. 2006;24:805-811. 57. langman g, hall pm, todd g. role of non-alcoholic steatohepatitis in methotrexate-induced liver injury. j gastroenterol hepatol. 2001;16:13951401. 58. rosenberg p, urwitz h, johannesson a, et al. psoriasis patients with diabetes type 2 are at high tisk of developing liver fibrosis during methotrexate treatment. j hepatol. 2007;46:11111118. 59. weinstein g, roenigk h, maibach h, et al. psoriasis-liver-methotrexate interactions. arch dermatol. 1973;108:36-42. 60. shibata n, hayakawa t, hoshino n, et al. effect of obesity on cyclosporine trough concentrations in psoriasis patients. am j health syst pharm. 1998;55: 1598-1602. 61. maza a, montaudié h, sbidian e, et al. oral cyclosporin in psoriasis: a systematic review on treatment modalities, risk of kidney toxicity and evidence for use in non-plaque psoriasis. j eur acad dermatol venereol. 2011;25:19-27. 62. thaci d, bräutigam m, kaufmann r, et al bodyweight-independent dosing of skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 378 cyclosporine micro-emulsion and three times weekly maintenance regimen in severe psoriasis. a randomised study. dermatology. 2002;205:383-388. 63. wakkee m, thio hb, prens ep, et al. unfavorable cardiovascular risk profiles in untreated and treated psoriasis patients. atherosclerosis. 2007;190:1-9. 64. reich k, gottlieb ab, kimball a, et al. consistency of infliximab response across subgroups of patients with psoriasis: integrated results from randomized clinical trials. j am acad dermatol. 2006;54(suppl 1):ab215. 65. weisman mh, moreland lw, furst de, et al. efficacy, pharmacokinetic, and safety assessment of adalimumab, a fully human anti-tumor necrosis factoralpha monoclonal antibody, in adults with rheumatoid arthritis receiving concomitant methotrexate: a pilot study. clin ther. 2003;25:1700-1721. 66. papoutsaki m, chimenti ms, costanzo a, et al. adalimumab for severe psoriasis and psoriatic arthritis: an open-label study in 30 patients previously treated with other biologics. j am acad dermatol. 2007;57:269-275. 67. kragballe k, sygehus a, thaci d, et al. adalimumab plus topical treatment (calcipotriol/betamethasone) in the treatment of moderate to severe psoriasis: response across subgroups in believe. j am acad dermatol. 2010;62(suppl 1):ab133. 68. gordon k, korman n, frankel e, et al. efficacy of etanercept in an integrated multistudy database of patients with psoriasis. j am acad dermatol. 2006;54:s101-111. 69. strober b, gottlieb a, leonardi c, et al. levels of response of psoriasis patients with different baseline characteristics treated with etanercept. j am acad dermatol. 2006;54(3, suppl. 1):ab220. 70. saurat jh, unnebrik k, golblum o, et al. adalimumab response is consistent across subgroups of patients with moderate to severe psoriasis: subanalysis of the champion study. j am acad dermatol. 2010;62:ab124. 71. esposito m, mazzotta a, saraceno r, et al. influence and variation of the body mass index in patients treated with etanercept for plaque-type psoriasis. int j immunopathol pharmacol. 2009;22:219-225. 72. de groot m, appelman m, spuls pl, et al. intial experience with routine administration of etanercept in psoriasis. br j dermatol. 2006;155:808814. 73. duarte aa. moderate to severe psoriasis treated with infliximab-53 patients: patients profile, efficacy and adverse effects. an bras dermatol. 2011;86:257-263. 74. gisondi p, cotena c, tessari g, et al. anti-tumour necrosis factor-alpha therapy increases body weight in patients with chronic plaque psoriasis: a retrospective cohort study. j eur acad dermatol venereol. 2008;22:341-344. 75. saraceno r, schipani c, mazzotta a, et al. effect of anti-tumor necrosis factoralpha therapies on body mass index in patients with psoriasis. pharmacol res. 2008;57:290-295. 76. paul c, cather j, gooderham m, et al. efficacy and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in patients with moderate-to-severe plaque psoriasis over 52 weeks: a phase iii, randomized controlled trial (esteem 2). br j dermatol. 2015;173:1387-1399. 77. lebwohl m, yeilding n, szapary p, et al. impact of weight on the efficacy and skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 379 safety of ustekinumab in patients with moderate to severe psoriasis: rationale for dosing recommendations. j am acad dermatol. 2010;63:571-579. 78. martin da, towne je, kricorian g. the emerging role of il-17 in the pathogenesis of psoriasis: preclinical and clinical findings. j invest dermatol. 2013;133(1):17-26. 79. papp ka, langley rg, sigurgeirsson b, et al. efficacy and safety of secukinumab in the treatment of moderate-to-severe plaque psoriasis: a randomized, doubleblind, placebo-controlled phase ii doseranging study. br j dermatol. 2013;168(2):412-421. 80. reich k, puig l, mallbris l, et al. the effect of 
bodyweight on the efficacy and safety of ixekizumab: results from an integrated database of 
three randomised, controlled phase 3 studies of patients with moderate-to-severe plaque psoriasis. j eur acad dermatol venereol. 2017;31(7):1196-1207. 81. papp ka, reich k, paul c, et al. a prospective phase iii, randomized, double-blind, placebo-controlled study of brodalumab in patients with moderate-to-severe plaque psoriasis. br j dermatol. 2016;175(2):273-286. skin september 2017 volume 1 issue 2 copyright 2017 the national society for cutaneous medicine 55 in-depth reviews psoriasis therapies and the risk of cutaneous malignancy emily e dando ba a , rina a anvekar md b a university of pittsburgh school of medicine, pittsburgh, pa b department of dermatology, mount sinai school of medicine, new york, ny psoriasis is a complex inflammatory disease that affects approximately 3.2% of us adults 1 . chronic inflammation associated with psoriasis is a risk factor for multiple medical comorbidities, including malignancy. several studies have revealed an increased abstract background: systemic therapies for moderate-to-severe psoriasis target the dysregulated inflammatory response. however, their immunomodulatory properties may also contribute to carcinogenesis, leading to an increased risk of cutaneous malignancy in patients exposed to systemic agents. objective: a review of the literature was performed to evaluate the risk of cutaneous malignancy associated with the following therapies for moderate-to-severe psoriasis: psoralen and ultraviolet a (puva), ultraviolet b (uvb), cyclosporine, methotrexate, retinoids, tnf-α inhibitors, il-12/23 inhibitors, and il-17 inhibitors. results: rates of non-melanoma skin cancer (nmsc), most notably squamous cell carcinoma (scc), increase linearly with the number of puva exposures. uvb radiation, both narrowband and broadband, has no clear association with skin cancer. there is a wellcharacterized association between cyclosporine and nmsc, particularly sccs, although it is less clear whether cyclosporine predisposes to malignant melanoma. methotrexate appears to increase the risk of melanoma and nmsc in a dose-dependent fashion. retinoids, on the other hand, have chemopreventative properties and may decrease the risk of nmsc in patients with psoriasis. a large body of evidence supports an increased risk of nmsc, particularly scc, in tnf-α inhibitors, but an association with melanoma is less clear. the newly-developed agents, il-12/23 and il-17 inhibitors, do not clearly show an increased carcinogenic risk, but their long-term safety profiles are still under investigation. conclusions: many systemic psoriasis therapies, including puva, cyclosporine, methotrexate, and tnf-α inhibitors, appear to increase the risk of cutaneous malignancy. when prescribing these agents, physicians must weigh the benefit of treatment with their carcinogenic potential. additional post-marketing surveillance is required to better understand the long-term risks of the newer biologic agents. introduction skin september 2017 volume 1 issue 2 copyright 2017 the national society for cutaneous medicine 56 incidence of skin, lymphohematopoietic, and solid cancers in this population 2 . this risk arises independently of exposure to systemic agents. in a cohort of 186,076 patients with mild psoriasis (defined as never receiving systemic therapy), there was a small but significant increase in nonmelanoma skin cancer (nmsc) [adjusted hazard ratio (ahr) 1.09, 95% confidence interval (ci) 1.05-1.13] and all other cancers (ahr 1.06, 95% ci 1.02-1.09) compared to ageand gender-matched controls 3 . an increased risk of nmsc was also recently observed in large cohorts of psoriasis patients in the united states and taiwan 4,5 . in addition to the intrinsic risk of malignancy associated with the psoriasis disease state, patients with psoriasis are also exposed to several therapies with carcinogenic potential. approximately 25% of psoriasis patients have moderate (3-10%) to severe (>10%) body surface area involvement, often requiring systemic therapy. treatment options include phototherapy (ultraviolet b radiation and psoralen and ultraviolet a), systemic non-biologic immunosuppressants (cyclosporine, methotrexate, and retinoids), and biologic agents that inhibit specific targets of the inflammatory pathway (tnf-α, il-12/23, and il-17 inhibitors). these immunomodulatory therapies target the dysregulated inflammatory response in psoriasis, but also may contribute to carcinogenesis. a review of the literature was performed to evaluate the risk of malignancy associated with the above systemic agents. the long-term safety profile of puva has been studied most comprehensively by stern et al. through the puva follow-up study, which prospectively followed 1,380 patients with moderate-to-severe psoriasis. three decades of follow-up have revealed an increased risk of nmsc, particularly squamous cell carcinoma (scc), in puvatreated patients 6 . 351 participants (25%) developed a total of 2,973 sccs, corresponding to a 32 times greater incidence (95% ci 30.8-33.1) of scc compared to ageand gender-matched controls. scc risk increases linearly with the number of exposures, most notably after 150 treatments. basal cell carcinoma (bcc) risk is less pronounced than scc risk but still 4.7 times higher (95% ci 4.5-4.9) than the general population. nmsc risk is further amplified with prior or concomitant exposure to other carcinogens, including methotrexate and cyclosporine, and decreased with active oral retinoid use 6-8 . scc risk does not significantly decrease even 15 years after discontinuation of therapy 9 . several retrospective studies of the dutch, swedish, and finnish cancer registries also demonstrate a dose-dependent increased risk of nmsc, primarily scc, in puva-exposed patients, although reported risks were not as high as described in the united states cohort 10-12 . puva also stimulates melanocyte hyperplasia, predisposing to atypical pigmented lesions. there is a small but significant increased risk of melanoma in puva-treated patients compared to age and sex-adjusted controls (rr = 2.3, 95% ci 1.1-4.1) 13 . this risk is amplified in patients at least 15 years from their first puva treatment (irr = 5.9, 95% ci 2.2-15.9) and in those who received at least 200 puva treatments (irr = 2.0, 95% ci 0.9-9.5), although the latter result was not statistically significant 14 . however, the association between malignant melanoma and puva is not as clear as that described for nmsc, psoralen and ultraviolet a (puva) skin september 2017 volume 1 issue 2 copyright 2017 the national society for cutaneous medicine 57 and all of the major retrospective european studies reported no increased risk of malignant melanoma in puvatreated patients 10-12 . uvb phototherapy includes broadband (280320 nm) and narrowband (311-313 nm) radiation. narrowband uvb (nb-uvb) was developed after studies demonstrated that wavelengths below 300 nm are more likely to produce burns, while wavelengths above 313 nm are not effective in clearing psoriasis. the optimized anti-psoriatic to erythemogenic ratio in nb-uvb promotes more rapid clearance and longer remission than broadband uvb (bb-uvb) 15 . although natural sunlight is a known carcinogen, several studies suggest that bbuvb therapy does not appreciably increase carcinogenesis in patients with psoriasis. a systematic review of 11 studies involving 3,400 patients revealed no increased risk of nmsc or melanoma in bb-uvb-treated patients 16 . the puva follow-up study initially demonstrated no association between nmsc and long-term exposure to uvb or topical tar. however, a later study published after an additional 14 years of data collection suggested that high uvb exposure, defined as greater than 300 treatments, was associated with a small but significant increased risk of scc (adjusted irr = 1.37, 95% ci 1.03-1.83) and bcc (adjusted irr = 3.00, 95% ci 1.30-6.91) in puva-treated patients 17 . of note, an increased risk of genital tumors has also been observed in men treated with puva or uvb without genital shielding 18 , which has subsequently become standard practice. bb-uvb may be used alone or in combination with topical tar with no appreciable increase in skin cancer risk 19 . nb-uvb therapy also does not appear to increase the incidence of nmsc or melanoma. in the largest study to date of 3,867 patients treated with nb-uvb in scotland, half of whom had psoriasis, no significant association with scc, bcc, or melanoma was detected 20 . the carcinogenic potential of cyclosporine has been well characterized in posttransplant patients on immunosuppressive regimens. the risk of nmsc, particularly scc, rises proportionally with duration of treatment and is as high as 47.1% after 20 years of immunosuppressive therapy 21 . interestingly, the risk of nmsc appears higher on sun-exposed skin, suggesting that immunosuppression may promote uv radiation-mediated carcinogenesis 22 . murine experimental models also suggest that cyclosporine promotes tumor growth independently of its effect on host immunity through several direct cellular mechanisms, including promoting invasiveness of nontransformed cells 23 . an increased risk of nmsc is evident in psoriasis patients on cyclosporine as well. a cohort of 1,252 patients with severe psoriasis demonstrated a 6-fold higher incidence of cutaneous malignancies, mostly scc, in patients treated with cyclosporine compared to the general population after 5 years (sir = 6.2, 95% ci 3.8-9.5) 24 . patients treated with cyclosporine for more than 2 years showed an elevated risk of nmsc over those treated for shorter periods (rr = 3.3, 95% ci 1.3-8.4). prior exposure to puva, methotrexate, or immunosuppressants also significantly amplified risk of nmsc. several case reports suggest an association between cyclosporine and malignant ultraviolet b (uvb) cyclosporine skin september 2017 volume 1 issue 2 copyright 2017 the national society for cutaneous medicine 58 melanoma 25,26 . however, this observation has not been substantiated in larger studies 24 . methotrexate appears to increase the risk of nmsc in a dose-dependent manner. in a recently-published study of 405 patients with rheumatoid arthritis or psoriatic arthritis, patients who received methotrexate doses above 8,000 mg developed nmsc at a rate almost 5-times that of patients never exposed to methotrexate (sir 4.81, 95% ci 3.60-6.29). this risk drops to 2-fold in patients with cumulative doses less than 5,000 mg (sir 2.31, 95% ci 1.58-2.36). in the puva follow-up study, exposure to at least two years of methotrexate increased scc risk by an additional 2.4-fold (95% ci 2.13-2.79). however, some studies have shown no association between methotrexate exposure and nmsc 27 . methotrexate may also increase melanoma risk. in a cohort of 459 rheumatoid arthritis patients receiving methotrexate, a 3-fold (sir = 3.0, 95% ci 1.2-6.2) increased risk of melanoma was observed compared to the general population after an average follow up of 9.3 years 28 . recently, a small but significant increased risk of cutaneous melanoma was detected in patients to whom methotrexate was dispensed from swedish pharmacies when compared to ageand sex-matched controls (hr 1.17, 95% ci 1.08-1.26) 29 . retinoids have been studied extensively for their chemopreventive properties. they protect against malignant transformation by limiting cell cycle progression, promoting apoptosis of cancer cells, and downregulating proto-oncogenes 30 . systemic retinoids have demonstrated efficacy in preventing nmsc formation in high risk populations like organ transplant recipients or patients with genodermatoses such as xeroderma pigmentosum or basal cell nevus syndrome 31,32 . in a randomized controlled trial of 44 renal transplant recipients, 11% of patients treated with 30 mg/day of acitretin for 6 months developed two new sccs, while 47% of patients receiving placebo developed 18 new sccs 32 . the chemoprotective benefit of systemic retinoids seems to apply only for the duration of therapy. five patients with xeroderma pigmentosum showed 63% (p=0.019) reduction of cutaneous tumor burden during two years of high-dose oral isotretinoin therapy, from 121 tumors in the two years proceeding therapy to 25 tumors during treatment. however, during one year of continued observation after discontinuation of isotretinoin, the tumor burden increased 8.5-fold (p=0.007) over that observed during the treatment period, returning to pre-treatment levels 31 . low-dose systemic retinoid regimens were developed in an attempt to limit side effects but appear less effective overall 33 . however, one study did demonstrate a significant chemoprotective effect of low-dose (0.3 mg/kg) daily acitretin in renal transplant patients for up to 4 years of treatment 34 . topical regimens also do not appear efficacious in preventing malignancy. recently, a randomized controlled trial of 1,131 patients from the veterans affairs system with a 5-year history of 2 or more nmscs showed no statistically significant benefit of 0.1% topical tretinoin in precluding development of invasive nmsc or actinic keratosis 35 . methotrexate retinoids skin september 2017 volume 1 issue 2 copyright 2017 the national society for cutaneous medicine 59 tnf-α inhibitors are effective therapies for a variety of immune-mediated diseases, but tnf-α also facilitates the immune response against tumor cells via dendritic cell activation and tumor cell apoptosis. in murine tumor cells, transduction with the human tnf-α gene promotes tumor regression, an effect that is reversed following treatment with anti-tnf-α antibody 36 . the carcinogenic potential of tnf-α inhibitors has been studied most extensively in rheumatoid arthritis patients. a large meta-analysis of 74 randomized controlled trails of the tnf-α inhibitors adalimumab, etanercept, and infliximab revealed a 2.02 relative risk (95% ci 1.11-3.95) of nmsc in 15,418 pooled patients on tnf-α inhibitors compared to 7,486 comparators at a median duration of <6 months 37 . a systematic review and meta-analysis of four studies encompassing over 29,000 patients revealed a 45% increased risk of nmsc in patients treated with tnf-α inhibitors compared to those receiving non-biologic therapy (relative risk = 1.45, 95% ci 1.151.76) 38 . a recently-published study of 5,889 patients within the kaiser permanente northern california health plan assessed malignancy rates among patients receiving systemic therapy for psoriasis 39 . the cohort was subdivided into those treated with at least one biologic and those treated exclusively with non-biologic systemic agents. scc rates were increased 81% among biologic users (ahr 1.81, 95% ci 1.23-2.675), 97% of whom were treated with tnf-α inhibitors. conversely, bcc and melanoma rates were comparable among biologic and nonbiologic users (bcc ahr = 1.23, 95% ci 0.91-1.66; melanoma ahr = 1.57, 95% ci 0.61-4.09). larger studies have consistently failed to show a significantly increased risk of melanoma in patients treated with tnf-α inhibitors 38,40 . il-12 and il-23 are inflammatory cytokines that contribute to the aberrant immune response in psoriasis. il-12 promotes th1helper cell differentiation and the production of interferon by natural killer cells. il-23 stimulates th17 cells, whose effector cytokines are thought to promote keratinocyte proliferation. pre-clinical models have produced conflicting data on whether il-12 and il-23 promote or protect against tumor development. ustekinumab, a fully human monoclonal antibody that inhibits the p40 subunit of il12 and il-23, was approved in september 2009 for the treatment of moderate-tosevere plaque psoriasis. in short-term, placebo-controlled clinical trials of ustekinumab, rates of nmsc were comparable among patients receiving placebo (1.13/100 patient-years, 95% ci 0.14-4.09), 45 mg ustekinumab doses (0.49/100 patient-years, 95% ci 0.01-2.75), and 90 mg ustekinumab doses (0.98/100 patient-years, 95% ci 0.12-3.55) through 3 years 41 . safety data pooled from four studies of 3,117 psoriasis patients found the rate of nmsc was 0.64 (0.41-0.95) and 0.44 (0.28-0.66) per 100 patient-years for 45 mg and 90 mg doses of ustekinumab, respectively, after up to 5 years of followup 42 . these rates are comparable to but lower than those reported for tnf-α inhibitors, which range from 0.7 to 1.17 per 100 patient-years. however, the il-12/23 tnf-a inhibitors il-12/23 inhibitors skin september 2017 volume 1 issue 2 copyright 2017 the national society for cutaneous medicine 60 inhibitors are too new to make conclusive statements regarding their safety profile. il-17 inhibitors are the newest biologics used to treat moderate-to-severe plaque psoriasis. th17 cells produce il-17 upon activation by il-23 from dendritic cells. some studies suggest that il-17 promotes inflammation-mediated tumor growth 43 , in which case inhibiting expression of il-17 or its upstream regulatory cytokine, il-23, could theoretically protect against carcinogenesis. however, other studies have described a protective role of il-17 in tumor immunity 44 . secukinumab is a fully human monoclonal antibody that was approved in january 2015. in data pooled from 10 phase ii/iii secukinumab psoriasis trials involving 3,993 subjects, the incidence of nmsc was comparable in the first 12 weeks among patients receiving placebo (0.4, 95% ci 0.11.2), 150 mg secukinumab doses (0.17, 95% ci 0.03-0.68), or 300 secukinumab doses (0.09, 95% ci 0-0.55) 45 . four cases of melanoma were identified, all of which occurred in patients at increased risk based on medical history or prior exposure to immunosuppressive agents. ixekizumab was recently approved in march 2016 and brodalumab in february 2017. long-term safety data is not yet available for these agents, and additional follow up is required to more accurately assess their risk of nmsc and melanoma. patients with psoriasis have an increased risk of several malignancies, which is amplified by exposure to certain systemic therapies. puva-treated patients exhibit higher rates of nmsc, most notably scc, which increase linearly with the number of exposures. melanoma risk is amplified in patients at least 15 years from their first puva treatment and in those who received at least 200 puva treatments. uvb radiation, both narrowband and broadband, has no clear association with skin cancer. there is a well-characterized association between cyclosporine and nmsc, particularly sccs, although it is less clear whether cyclosporine predisposes to malignant melanoma. methotrexate appears to increase the risk of melanoma and nmsc in a dose-dependent fashion. retinoids, on the other hand, have chemopreventative properties and may decrease the risk of nmsc in patients with psoriasis. biologic agents, including tnf-α, il-12/23, and il-17 inhibitors, target specific components of the inflammatory pathway. these agents have proven very effective in treating psoriasis, so much so that psoriasis area severity index (pasi) 90 scores are now achievable targets in newer clinical trials. a large body of evidence supports an increased risk of nmsc, particularly scc, in tnf-α inhibitors, but an association with melanoma is less clear. the newly-developed agents, il-12/23 and il-17 inhibitors, do not clearly show an increased carcinogenic risk, but their longterm safety profiles are still under investigation. interestingly, the ratio of bcc to scc observed thus far in these agents approximates that of the general population (4:1). in contrast, a scc predominance has historically been observed in patients on immunosuppressive therapy, like cyclosporine and tnf-α inhibitors. it is possible that this observation may reflect a il-17 inhibitors conclusions skin september 2017 volume 1 issue 2 copyright 2017 the national society for cutaneous medicine 61 lower degree of immunosuppression and lower malignancy risk in patients treated with il-12/23 or il-17 inhibitors. however, additional postmarketing surveillance is required to better understand their long-term risks. until more comprehensive data are available, physicians must weigh the benefit of treatment with the possibly underestimated carcinogenic potential of these newer agents. conflict of interest disclosures: none. funding: none. corresponding author: emily dando university of pittsburgh school of medicine office of student affairs 3550 terrace street suite 594, scaife hall pittsburgh, pa 15261 412-251-7154 dando.emily@medstudent.pitt.edu references: 1. rachakonda, t.d., c.w. schupp, and a.w. armstrong, psoriasis prevalence among adults in the united states. j am acad dermatol, 2014. 70(3): p. 512-6. 2. pouplard, c., et al., risk of cancer in psoriasis: a systematic review and metaanalysis of epidemiological studies. j eur acad dermatol venereol, 2013. 27 suppl 3: p. 36-46. 3. chiesa fuxench, z.c., et al., the risk of cancer in patients with psoriasis: a populationbased cohort study in the health improvement network. jama dermatol, 2016. 152(3): p. 282-90. 4. chen, y.j., et al., the risk of cancer in patients with psoriasis: a population-based cohort study in taiwan. j am acad dermatol, 2011. 65(1): p. 84-91. 5. kimball, a.b., et al., incidence rates of malignancies and hospitalized infectious events in patients with psoriasis with or without treatment and a general population in the u.s.a.: 2005-09. br j dermatol, 2014. 170(2): p. 366-73. 6. stern, r.s. and p.f.-u. study, the risk of squamous cell and basal cell cancer associated with psoralen and ultraviolet a therapy: a 30-year prospective study. j am acad dermatol, 2012. 66(4): p. 553-62. 7. marcil, i. and r.s. stern, squamous-cell cancer of the skin in patients given puva and ciclosporin: nested cohort crossover study. lancet, 2001. 358(9287): p. 1042-5. 8. nijsten, t.e. and r.s. stern, oral retinoid use reduces cutaneous squamous cell carcinoma risk in patients with psoriasis treated with psoralen-uva: a nested cohort study. j am acad dermatol, 2003. 49(4): p. 644-50. 9. nijsten, t.e. and r.s. stern, the increased risk of skin cancer is persistent after discontinuation of psoralen+ultraviolet a: a cohort study. j invest dermatol, 2003. 121(2): p. 252-8. 10. lindelof, b., et al., puva and cancer risk: the swedish follow-up study. br j dermatol, 1999. 141(1): p. 108-12. 11. bruynzeel, i., et al., 'high single-dose' european puva regimen also causes an excess of non-melanoma skin cancer. br j dermatol, 1991. 124(1): p. 49-55. 12. hannuksela-svahn, a., et al., psoriasis, its treatment, and cancer in a cohort of finnish patients. j invest dermatol, 2000. 114(3): p. 587-90. 13. stern, r.s., k.t. nichols, and l.h. vakeva, malignant melanoma in patients treated for psoriasis with methoxsalen (psoralen) and ultraviolet a radiation (puva). the puva follow-up study. n engl j med, 1997. 336(15): p. 1041-5. 14. stern, r.s. and p.f.u. study, the risk of 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melanoma occurring after cyclosporine a therapy. br j dermatol, 1991. 124(6): p. 611. 26. merot, y., et al., cutaneous malignant melanomas occurring under cyclosporin a therapy: a report of two cases. br j dermatol, 1990. 123(2): p. 237-9. 27. chakravarty, e.f., k. michaud, and f. wolfe, skin cancer, rheumatoid arthritis, and tumor necrosis factor inhibitors. j rheumatol, 2005. 32(11): p. 2130-5. 28. buchbinder, r., et al., incidence of melanoma and other malignancies among rheumatoid arthritis patients treated with methotrexate. arthritis rheum, 2008. 59(6): p. 794-9. 29. polesie, s., et al., methotrexate treatment and risk for cutaneous malignant melanoma: a retrospective comparative registry-based cohort study. br j dermatol, 2016. 30. carr, d.r., j.j. trevino, and h.b. donnelly, retinoids for chemoprophylaxis of nonmelanoma skin cancer. dermatol surg, 2011. 37(2): p. 129-45. 31. kraemer, k.h., et al., prevention of skin cancer in xeroderma pigmentosum with the use of oral isotretinoin. n engl j med, 1988. 318(25): p. 1633-7. 32. bavinck, j.n., et al., prevention of skin cancer and reduction of keratotic skin lesions during acitretin therapy in renal transplant recipients: a double-blind, placebo-controlled study. j clin oncol, 1995. 13(8): p. 1933-8. 33. tangrea, j.a., et al., long-term therapy with low-dose isotretinoin for prevention of basal cell carcinoma: a multicenter clinical trial. isotretinoin-basal cell carcinoma study skin september 2017 volume 1 issue 2 copyright 2017 the national society for cutaneous medicine 63 group. j natl cancer inst, 1992. 84(5): p. 328-32. 34. mckenna, d.b. and g.m. murphy, skin cancer chemoprophylaxis in renal transplant recipients: 5 years of experience using lowdose acitretin. br j dermatol, 1999. 140(4): p. 656-60. 35. weinstock, m.a., et al., tretinoin and the prevention of keratinocyte carcinoma (basal and squamous cell carcinoma of the skin): a veterans affairs randomized chemoprevention trial. j invest dermatol, 2012. 132(6): p. 1583-90. 36. asher, a.l., et al., murine tumor cells transduced with the gene for tumor necrosis factor-alpha. evidence for paracrine immune effects of tumor necrosis factor against tumors. j immunol, 1991. 146(9): p. 3227-34. 37. askling, j., et al., cancer risk with tumor necrosis factor alpha (tnf) inhibitors: meta analysis of randomized controlled trials of adalimumab, etanercept, and infliximab using patient level data. pharmacoepidemiol drug saf, 2011. 20(2): p. 119-30. 38. mariette, x., et al., malignancies associated with tumour necrosis factor inhibitors in registries and prospective observational studies: a systematic review and metaanalysis. ann rheum dis, 2011. 70(11): p. 1895-904. 39. asgari, m.m., et al., malignancy rates in a large cohort of patients with systemically treated psoriasis in a managed care population. j am acad dermatol, 2017. 76(4): p. 632-638. 40. wolfe, f. and k. michaud, biologic treatment of rheumatoid arthritis and the risk of malignancy: analyses from a large us observational study. arthritis rheum, 2007. 56(9): p. 2886-95. 41. gordon, k.b., et al., long-term safety experience of ustekinumab in patients with moderate to severe psoriasis (part ii of ii): results from analyses of infections and malignancy from pooled phase ii and iii clinical trials. j am acad dermatol, 2012. 66(5): p. 742-51. 42. papp, k.a., et al., long-term safety of ustekinumab in patients with moderate-tosevere psoriasis: final results from 5 years of follow-up. br j dermatol, 2013. 168(4): p. 844-54. 43. numasaki, m., et al., interleukin-17 promotes angiogenesis and tumor growth. blood, 2003. 101(7): p. 2620-7. 44. benchetrit, f., et al., interleukin-17 inhibits tumor cell growth by means of a t-cell dependent mechanism. blood, 2002. 99(6): p. 2114-21. 45. van de kerkhof, p.c., et al., secukinumab long-term safety experience: a pooled analysis of 10 phase ii and iii clinical studies in patients with moderate to severe plaque psoriasis. j am acad dermatol, 2016. 75(1): p. 83-98 e4. skin july 2018 volume 2 issue 4 copyright 2018 the national society for cutaneous medicine 214 original research scarring alopecia: the attitudes, knowledge, and referral patterns of hair stylists and barbers julia accetta bs a , aderonke obayomi bs a , rachel evers-meltzer md b , virginia alldredge md a , andrea murina md a a department of dermatology,tulane university school of medicine b department of dermatology, boston medical center the most common hair complaints seen by dermatologists include progressive thinning and excessive shedding of the scalp hair. complaints may include decrease in hair coverage, inability to maintain hairstyle, or extreme thinning of ponytail size. 1 the delayed detection and diagnosis of alopecia may be detrimental for scarring alopecias such as central centrifugal cicatricial alopecia (ccca) and lichen planopilaris because hair regrowth can rarely occur if treated very early. 2 hair loss is often a significant source of psychological distress and therefore emphasis should be placed on early detection and referral for counseling. 3 research has shown that using beauty salons as a setting for implementing health promotion programs capitalizes on the relationships hairdressers have with their clients. stylists are in a unique position to detect scalp anomalies because they routinely assess this area during a client appointment. interventions targeting the education, detection and physician referral abstract disorders of hair loss are commonly encountered by hair stylists, who are in a unique position to identify early signs and symptoms. the goals of this study were to assess hair stylists’ knowledge of and propensity to refer patients with scarring alopecias. one-hundredeighteen stylists completed surveys to this effect. the majority of respondents (66.1%) stated that they had been asked by clients to evaluate for hair loss, whereas approximately half reported routinely referring clients with hair loss to a dermatologist. although knowledge of alopecia varied, the vast majority indicated they would be willing to undergo further training in identifying hair loss disorders and would be willing to discuss this information with clients. these results demonstrate that hairdressers frequently interact with patients suffering from hair loss and that many are receptive to receiving additional training to ensure proper identification and prompt referral. introduction skin july 2018 volume 2 issue 4 copyright 2018 the national society for cutaneous medicine 215 of melanoma, hypertension, breast cancer, and prostate cancer have successfully utilized hairdressers. 4-7 this study was approved for exempt review by the tulane university institutional review board. cross-sectional data were obtained via questionnaire administered to certified hairdressers at 51 salons in the new orleans metropolitan area. the majority of salons, with the exception of four barbershops, serviced both men and women. blank surveys were given to all employees at each establishment and were collected forty eight hours later. surveys were received from 118 respondents. response rate is unknown. our findings indicate that many hairdressers already examine their clients for hair loss and about half of the time they will refer their client to a dermatologist. table 1 provides hairdressers’ hair loss detection and referral practices. table 2 provides hair stylist beliefs of permanent versus non-permanent alopecia. most hairdressers (66.1%) responded that they have been asked by clients to examine them for hair loss. when hairdressers notice hair loss, almost half of the respondents (49.2%) refer their client to a dermatologist. most respondents (68.6%) received some form of hair loss training while in beauty school, though most were largely unfamiliar with the most common types of alopecia. the majority (79.7%) of hairdressers were willing to learn more about the different types of hair loss and a larger portion of respondents (90.7%) indicated that they would be willing to discuss hair loss with their clients if they were trained to identify the different types of hair loss. of the five education modes surveyed, respondents preferred attending a continuing education seminar or using the internet to receive further information. overall, the majority of stylists responded that they believe a scalp exam by a hairdresser is helpful for finding the cause of hair loss and some even reported having a client return with a medical diagnosis. the study identified key knowledge deficits in detecting specific hair loss patterns among hair stylists and barbers. while most stylists received some form of hair loss training in beauty school, the majority of respondents were generally unfamiliar with the eleven listed alopecia subtypes despite reporting confidence in their ability to recognize permanent versus nonpermanent hair loss. the types of hair loss most familiar to the stylists included alopecia areata and androgenic alopecia. while this study provided a generalized descriptive overview of hairstylist knowledge of alopecia, further investigation is required and may include investigating the type of hair loss education provided by beauty schools. further research is also warranted to explore these trends in salons with predominantly african american clientele. methods results discussion skin july 2018 volume 2 issue 4 copyright 2018 the national society for cutaneous medicine 216 table 1. hairdressers’ hair loss detection and referral patterns, n=118 variable n % received training in beauty school about hair loss no 37 31.4 yes 81 68.7 know about the different types of hair loss (referred to in table 2) no 42 35.6 yes 76 64.4 frequency that clients ask stylists to examine them for hair loss never 40 33.9 yearly 15 12.7 monthly 41 34.7 weekly 16 13.6 daily 6 5.1 frequency that stylists have noticed permanent hair loss regardless of client asking never 23 19.5 yearly 31 26.3 monthly 42 35.5 weekly 16 13.6 daily 6 5.1 frequency stylist refers client to a doctor after noticing unusual hair loss never noticed 8 6.8 rarely 31 26.3 about half the time 20 16.9 most or every time 59 50 client came back with medical diagnosis after doctor referral never made a referral 17 14.4 no 68 57.6 yes 33 28.0 confidence in ability to identify permanent vs nonpermanent hair loss not at all confident 41 34.7 somewhat confident 59 50 very confident 18 15.3 believe scalp exam by a hairdresser is effective in hair loss detection not at all helpful 21 17.8 somewhat helpful 67 56.8 very helpful 30 25.4 interest in learning more about hair loss no 24 20.3 yes 94 79.7 willingness to educate clients on hair loss no 11 9.3 yes 107 90.7 preferred source for learning about hair loss internet 45 38.1 lecture 19 16.1 pamphlet 11 9.3 video 24 20.3 continuing education 56 47.5 skin july 2018 volume 2 issue 4 copyright 2018 the national society for cutaneous medicine 217 table 2. hair stylist beliefs of permanent versus non-permanent alopecia, n=118 permanent (%) not permanent (%) not familiar (%) telogen effluvium 2.54 12.7 84.7 anagen effluvium 0.85 16.1 83.1 central centrifugal cicatricial alopecia* 21.2 15.2 63.6 alopecia areata 36.4 29.6 33.9 discoid lupus erythematosus* 14.4 6.77 78.8 frontal fibrosing alopecia 21.2 17.8 61 male pattern baldness (androgenic alopecia) 65.3 8.47 26.2 lichen planopilaris* 2.54 9.32 88.1 folliculitis decalvans* 6.78 7.62 85.6 traction alopecia 16.1 25.4 58.5 *hair loss pattern associated with permanent, scarring alopecia because certain types of scarring alopecia, such as ccca, are more predominant in african americans, the knowledge and attitudes of the hairstylists serving this population would be particularly valuable when developing new training programs. lastly, including images and descriptions in addition to names of the various alopecias may be better understood by hair stylists unfamiliar with medical terminology. in summary, hairdressers frequently interact with patients suffering from hair loss and many provide product recommendations and physician referrals. these results provide evidence that most stylists are engaged in alopecia screening and education and that most are receptive to additional training to expand this role. this suggests that training hairdressers in alopecia screening and patient education may be a worthwhile and promising opportunity for early detection of irreversible hair loss and prompts further investigation. conflict of interest disclosures: none funding: none corresponding author: rachel evers-meltzer, md, mph department of dermatology boston university school of medicine boston medical center 609 albany street boston, ma 02118 617-638-5500 (office) 617-638-7289 (fax) rachel.eversmeltzer@bmc.org references: 1. mubki t, rudnicka l, olszewska m, shapiro j. evaluation and diagnosis of the hair loss patient: part i. history and clinical examination. j am acad dermatol. 2014;71(3):415.e1-15. 2. hamilton t, otberg n, wu wy, martinka m, shapiro j. successful hair re-growth with multimodal treatment of early cicatricial alopecia in discoid lupus erythematosus. acta derm venereol 2009;89:417-8. conclusions skin july 2018 volume 2 issue 4 copyright 2018 the national society for cutaneous medicine 218 3. hadshiew im, foitzik k, arck pc, paus r. burden of hair loss: stress and the underestimated psychosocial impact of telogen effluvium and androgenetic alopecia. j invest dermatol 2004;123:455-7. 4. roosta n, wong mk, woodley dt. utilizing hairdressers for early detection of head and neck melanoma: an untapped resource. j am acad dermatol. 2012;66(4):687-8. 5. victor rg, ravenell je, freeman a, leonard d, et al. effectiveness of a barber-based intervention for improving hypertension control in black men. arch intern med. 2011;171(4):342-50. 6. wilson te, fraser-white m, feldman j, et al. hair salon stylists as breast cancer prevention lay health advisors for african american and afrocaribbean women. j health care poor underserved. 2008;19(1):216-26. 7. luque js, rivers bm, kambon m, brookins r, et al. barbers against prostate cancer: a feasibility study for training barbers to deliver prostate cancer education in an urban african american community. j cancer educ. 2010;25:96-100. skin march 2018 volume 2 issue 2 copyright 2018 the national society for cutaneous medicine 132 pearls for the practitioner clinical photographs should accompany skin biopsies in many instances to improve patient care clay j. cockerell md, mba a a clinical professor of dermatology and pathology, director of dermatopathology, university of texas southwestern, dallas, tx the practice of dermatology has changed dramatically over the last 30 or more years since i began practice. the vast majority of patients who went to a dermatologist’s office were seen and treated by a board-certified dermatologist. dermatologists had the freedom to submit their skin biopsies to whomever they chose with no interference from third-party payers or organizations such as hospitals or private equity groups who might own their practices. most dermatologists were taught that performing punch biopsies was the preferred method for sampling inflammatory skin diseases and that incision, deep saucerization or excision techniques were to be used for sampling neoplasms. for many reasons such as progressive cuts in reimbursement, dermatologists have had to leverage their time by hiring non-physicians to extend their time for their practices to remain profitable. others have chosen to add additional services to their practices such as cosmetic dermatology which may cause them to have less time to spend on routine things such as evaluating potential neoplasms. while many extenders who send specimens to our laboratory are among the best clinicians we serve, others have had less training and are not skilled in the performance of skin biopsies with limited ability to provide clinical information. 1 furthermore, patients with skin diseases may be evaluated by physicians with little or no training in dermatology. the clinical information submitted for the dermatopathologist to use to correlate with the histologic findings is often woefully inadequate. 2 inflammatory dermatoses, often widespread with unusual patterns challenging even to a seasoned expert, are commonly submitted as “rash.” neoplasms are commonly submitted with a diagnosis of “neoplasm of uncertain behavior” when the differential diagnosis includes serious conditions such as melanoma. in many cases, this is because reimbursement from third party payers differs between benign and malignant diagnoses and keeping the diagnosis unclear until the histologic diagnosis is rendered allows the charge to be submitted as a benign or malignant process. many of these clinical diagnoses are generated robotically by an electronic medical record (emr) that offers a menu of phrases to be applied to any lesion. we receive requisitions from some practices where all melanocytic lesions are submitted as “irregular multi-colored lesion. r/o mm.” in many of these, the diagnosis is a banal intradermal nevus so that it would have been impossible for it to have simulated melanoma. in other cases, especially from non-dermatologists, an icdskin march 2018 volume 2 issue 2 copyright 2018 the national society for cutaneous medicine 133 10 code is written on the requisition form with no description at all. in others, no clinical information is submitted other than the patient's name and insurance information. thus, the fundamental hallmark of accurate diagnosis in dermatology, clinicopathologic correlation, has been steadily eroding which has been documented on more than one occasion. 2 while this may seem like an unfortunate and perhaps inevitable development, it has significant consequences for patients and clinicians who may find themselves in medico-legal jeopardy from delay in or failure to make accurate diagnoses. furthermore, with the advent of online reviews, they are placing themselves at risk for patients complaining about their practice with attendant negative consequences, especially if they are not able to establish a diagnosis or require the patient return repeatedly for additional biopsies increasing cost and inconvenience. while these are adverse consequences for clinicians, there are also negative, and in many cases, unacceptable, consequences for hapless patients who may be harmed significantly. fortunately, there is a potential escape from this morass via clinical photography. the ideal way for an accurate diagnosis to be made is for the patient to be examined in the context of histologic findings. this classic “cpc” was the tradition of clinical diagnosis for many years where clinical features of a disease were correlated with anatomic features at autopsy. in dermatology, rather than the specimen at the morgue, the clinical features of the disease are those presenting in the patient in the dermatologist’s office and the pathology is represented in the skin biopsy rather than the autopsy. given that the dermatopathologist rarely has access to patients, clinical correlation has traditionally been performed via the information provided on the pathology requisition form. with the increasing adoption of emr systems, that information has become progressively less useful so that a better way for clinicians to communicate is via clinical photography. because digital photography is now so readily available, inexpensive and simple to transmit, it should be available in any challenging case and submitted to the dermatopathologist at the time of the skin biopsy. it is not necessary to submit photographs in all cases such as every potential basal cell carcinoma or intradermal nevus. however, a case could be made for at least photographically recording every skin lesion or condition at the time of biopsy in case histologic features prove to be challenging or do not correlate with clinical features. i have seen amelanotic melanomas submitted as “rule out bcc,” and when the clinician was notified, they described the lesion as a nondescript pink papule or nodule. i have lesions submitted as “seborrheic keratosis” found to be melanoma when examined histologically. i have also witnessed cases of alleged medical negligence where an erroneous histologic diagnosis was rendered that would have been averted had a clinical photograph been available for review. how should photographs be submitted? ideally, images should be taken with a high-quality digital camera with excellent lighting. images taken with a smartphone, while less preferable, may still be valuable, however. in the case of neoplasms, a dermatoscopic image can be useful. digital images must be transmitted using secure encryption but if that is not possible, submitting images that have been de-identified so that patient privacy is not compromised can be submitted by email or skin march 2018 volume 2 issue 2 copyright 2018 the national society for cutaneous medicine 134 text. finally, if it is not convenient to submit clinical images digitally, a print photograph can be provided. while a series of pictures is preferable to a single one, anything is usually better than nothing as images allow the dermatopathologist to perform better clinical correlation. some referring clinicians have inquired if images stored in an emr can be submitted. while this would be convenient, unfortunately, many emr companies do not provide this feature or charge high fees making it a financially unrealistic for most. perhaps if dermatologists advocated stridently for this, it might be provided more readily. this could transform dermatology and dermatopathology at least to a degree. dermatopathologists would be expected to use their clinical diagnostic skills for pathologic correlation to render a diagnosis on the spot. the practice of “punting” the diagnostic process back to the clinician would become far less acceptable. dermatopathology fellows with training in pathology would have to work extra diligently in their fellowships to develop clinical dermatology skills as they will be expected to perform as well as those trained in dermatology residencies. our goal is to provide the best care for our patients and when technologies become available that makes us better, we are obligated to employ it. one has now become available that allows us to provide better care. the time has come for clinicians to use photography liberally by submitting photographs to dermatopathologists just as they do with their biopsy specimens. let’s start delivering better patient care through photography! conflict of interest disclosures: none. funding: none. corresponding author: clay cockerell, md 2110 research row, suite 100 dallas, tx 75235 800-309-0000 (office) ccockerell@dermpath.com references: 1. sellheyer, k., nelson, p., and bergfeld, w. nonspecific histopathological diagnoses: the impact of partial biopsy and the need for a consensus guideline. jama dermatol 150(1):11-2. 2. comfere, n., peters, m., jenkins, s., et al. dermatopathologists’ concern and challenges with clinical information in the skin biopsy requisition form: a mixed-methods study. j cutan pathol 2015(42): 333-345. skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 143 brief article atezolizumab caused pityriasis lichenoides-like drug eruption treated with narrowband ultraviolet b megan m perez, bs1, sebastian otto-meyer, ba1, cuong v. nguyen, md1, lida zheng, md1, jennifer choi, md1, lauren guggina, md2,3 1department of dermatology, northwestern university feinberg school of medicine, chicago, il 2harvard medical school, boston, ma 3department of dermatology, brigham and women’s hospital, boston, ma pityriasis lichenoides is a rare cutaneous disease, which exists along a spectrum with acute and chronic features.1 the acute form, pityriasis lichenoides et varioliformis acuta (pleva), presents as an abrupt onset of pruritic, erythematous, scaly, often crusted, macules, papules and vesicles, on the trunk and extremities. pityriasis lichenoides chronica (plc) typically presents with a more indolent, scaling erythematous papular eruption. we report a case of atezolizumab induced pityriasis lichenoides, with both acute and chronic features, which cleared with narrowband ultraviolet b (nbuvb) phototherapy treatment. a 68-year-old female with extensive-stage small cell lung cancer (sclc) presented with two weeks of a pruritic skin eruption. she had been diagnosed with sclc six months prior. she received four cycles of carboplatin/etoposide with the final dose approximately two months prior to presentation and palliative radiotherapy, followed by single agent atezolizumab every three weeks for maintenance therapy. after two doses of atezolizumab, she noted a diffuse pruritic eruption. physical exam showed numerous red, scaling 2-10millimeter papules of the arms and trunk (figure 1). abstract pityriasis lichenoides is a rare cutaneous disease that exists along a spectrum with acute and chronic features. the acute form, pityriasis lichenoides et varioliformis acuta (pleva), presents as a sudden onset scaly and often crusted, erythematous papular eruption. the chronic form, pityriasis lichenoides chronica, presents similarly but with a more indolent onset. this inflammatory condition can have numerous triggers, including infections and medications. however, checkpoint inhibitors, despite being associated with a wide variety of cutaneous adverse events, have only rarely been associated with a pityriasis lichenoides-like eruption. we report a case of drug-induced pityriasis lichenoides-like eruption secondary to checkpoint inhibitor atezolizumab that was successfully treated with narrowband ultraviolet b (nbuvb) light. to our knowledge, this is the first case of an atezolizumabinduced pityriasis lichenoides which responded well to nbuvb. introduction case presentation skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 144 figure 1. pityriasis lichenoides: clinical photograph of back drug-induced variant of pityriasis lichenoides, presenting with numerous erythematous slightly scaly papules coalescing into a large plaque in the central upper back with a second large plaque visible on the lower back. a punch biopsy of the arm showed a brisk interface process with overlying mounded parakeratosis alternating with an acute basket-weave stratum corneum. vacuolar alteration with associated lymphocytic exocytosis and necrotic keratinocytes were noted along with rare eosinophils and red blood cell extravasation. these histopathologic features favored an acute presentation of pityriasis lichenoides (figure 2). a drug-induced variant of pityriasis lichenoides was diagnosed secondary to atezolizumab. initially, she was treated with topical clobetasol 0.05% ointment and oral prednisone initially dosed at 0.5 mg/kg with improvement of her skin lesions. however, her systemic steroid course was held when she developed hypoxemic respiratory failure due to a parainfluenza pneumonia with concerns for a concurrent aspergillus pneumonia, for which she was started on empiric voriconazole. her eruption immediately flared off prednisone, though she continued topical clobetasol. a trial of minocycline was not tolerated due to nausea. she was ultimately initiated on nbuvb three times per week with clearance of her skin eruption after two months, followed by tapering off nbuvb therapy by 14 weeks. although she initially experienced burning pain with nbuvb therapy, this resolved with discontinuation of her voriconazole. her skin remains clear one year after her initial presentation. her sclc is stable with partial response 14 months after holding immunotherapy and she continues active surveillance with oncology. figure 2. histopathological features of pityriasis lichenoides from punch biopsy of arm shows a basketweave stratum corneum with serous crust and mounded parakeratosis. there is a robust vacuolar interface process with many necrotic keratinocytes and exocytosis of lymphocytes and red blood cells. the infiltrate is predominantly lymphohistiocytic with a rare eosinophil noted, consistent with a diagnosis of drug-induced pityriasis lichenoides, favoring the acute presentation, pleva. (h&e, 100x) atezolizumab is a programmed death-ligand1 (pd-l1) inhibitor approved for treatment of multiple cancers.2 immune checkpoint inhibitors have been reported to cause numerous cutaneous eruptions including discussion skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 145 lichenoid reactions, psoriasiform eruptions, vitiligo, eczema, subacute cutaneous lupus erythematosus (scle), and bullous pemphigoid.3 there is one report of plc-like drug eruption with another immune checkpoint inhibitor, pembrolizumab, during treatment of a 67-year-old woman with melanoma, which cleared with topical steroids.4 notably, our patient presented with more extensive distribution and increased confluence of the lesions along with severe associated pruritus and pathological findings more suggestive of pleva. our patient had a minimal response to topical steroids, and oral steroids were not a viable treatment option due to concerns for a fungal pneumonia. when considering treatments for drug induced pityriasis lichenoides, our patient presented unique therapeutic challenges given her complicated medical history. given her known extensive stage sclc and possible fungal pneumonia, treatment options were limited. first line treatments include topical treatments for pityriasis lichenoides include topical steroids and, less frequently, topical calcineurin inhibitors.1 however, treatment clearance (full or partial) for topical steroids is fifty percent or less in most case series and evidence for topical calcineurin inhibitors is based off of case reports.1,5 minocycline was initially chosen as a steroid sparing agent given our patients comorbidities. although a wide range of systemic agents have been used, most commonly antibiotics such as minocycline, tetracycline, and erythromycin are employed, with their success likely due to antiinflammatory properties. limited case series and reports indicate slightly higher efficacy than topical treatments alone, with most reporting a complete or partial response in the large majority of patients.1 systemic immunosuppressants such as corticosteroids or methotrexate are reserved for severe or recalcitrant cases, which were ultimately contraindicated given our patients ongoing infectious complications. nbuvb is an additional common treatment that may be used provided a patient does not have a medical contraindication, which include a history of light sensitive conditions such as lupus erythematosus or xeroderma pigmentosa.6 fortunately, our patient responded well to this therapy. to our knowledge this is the first reported case of an immune checkpoint inhibitor induced pityriasis lichenoides which responded well to nbuvb. it is also the first case with reported acute pityriasis lichenoides features. nbuvb has previously shown efficacy in pleva and plc.1 a retrospective study of pleva patients (n=23) found complete response to nbuvb in 65.2% of patients after 30-53 sessions, with all patients experiencing some response.7 reassuringly, only two patients experienced relapse with a mean follow-up time of 6.9 months. however, these findings cannot be fully extrapolated to our case, as they concern individuals with pleva often lasting years without a clear drug trigger noted. a final important consideration with nbuvb therapy this case raised, is the significant pain with phototherapy our patient experienced during concomitant voriconazole treatment, it is important to recognize that photosensitizing medications, such as voriconazole, may cause significant photosensitivity and likely resulted in the burning sensation during nbuvb.8 indeed, voriconazole is one of the most commonlyreported drugs associated with photosensitivity. appropriate counseling and discontinuation of therapy may be necessary in patients who experience these effects. we share this unique case to encourage the consideration of nbuvb therapy for pityriasis skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 146 lichenoides-like drug eruptions due to checkpoint inhibitors. abbreviations pleva – pityriasis lichenoides et varioliformis acuta nbuvb – narrowband ultraviolet b sclc – small cell lung cancer pd-l1 – program death ligand-1 scle – subacute cutaneous lupus erythematosus conflict of interest disclosures: none funding: none corresponding author: lauren guggina, md department of dermatology brigham and women’s hospital 221 longwood avenue boston, ma 02115 email: lguggina@bwh.harvard.edu references: 1. bellinato f, maurelli m, gisondi p, girolomoni g. a systematic review of treatments for pityriasis lichenoides. journal of the european academy of dermatology and venereology : jeadv. 2019;33(11):2039-2049. 2. 2. akinleye a, rasool z. immune checkpoint inhibitors of pd-l1 as cancer therapeutics. journal of hematology & oncology. 2019;12(1):92. 3. 3. sibaud v. dermatologic reactions to immune checkpoint inhibitors : skin toxicities and immunotherapy. american journal of clinical dermatology. 2018;19(3):345-361. 4. 4. mutgi ka, milhem m, swick bl, liu v. pityriasis lichenoides chronica-like drug eruption developing during pembrolizumab treatment for metastatic melanoma. jaad case reports. 2016;2(4):343-345. 5. 5. wahie s, hiscutt e, natarajan s, taylor a. pityriasis lichenoides: the differences between children and adults. br j dermatol. 2007;157(5):941-945. 6. 6. ultraviolet phototherapy management of moderate-to-severe plaque psoriasis: an evidence-based analysis. ont health technol assess ser. 2009;9(27):1-66. 7. 7. aydogan k, saricaoglu h, turan h. narrowband uvb (311 nm, tl01) phototherapy for pityriasis lichenoides. photodermatology, photoimmunology & photomedicine. 2008;24(3):128-133. 8. 8. kim wb, shelley aj, novice k, joo j, lim hw, glassman sj. drug-induced phototoxicity: a systematic review. journal of the american academy of dermatology. 2018;79(6):1069-1075. skin march 2018 volume 2 issue 2 copyright 2018 the national society for cutaneous medicine 150 brief articles disseminated cutaneous mycobacterium haemophilum infection and concomitant crusted scabies in an iatrogenically immunocompromised patient—a case report kristen tessiatore ms a , divya sadhwani md b , kimberly mancl md b , paul rodriguez-waitkus md phd b , lucia seminario-vidal md phd b a morsani college of medicine, university of south florida, tampa, fl b department of dermatology, university of south florida, tampa, fl mycobacterium haemophilum is a slowgrowing nontuberculous mycobacterium that causes skin and soft tissue infections in immunocompromised hosts. 1 between 1978 and 2010, fewer than 100 cases were reported. 2 likewise, crusted scabies is a rare infestation with the sarcoptes scabiei var hominis mite which occurs in immunocompromised patients. 3 while scabies infestation can be diagnosed with a scraping and direct microscopy, m. haemophilum infection poses a diagnostic challenge due to its broad clinical presentation, nonspecific histopathological findings, and culture requirements. 1,4 we report a case of concomitant m. haemophilum infection and scabies infestation in a 38-year-old woman on multiple immunosuppressive agents for dermatomyositis. this case highlights the unique presentation of two rare cutaneous diseases in an immunocompromised host, and aims to raise awareness regarding complications of immunosuppressive therapies. abstract mycobacterium haemophilum and crusted scabies are rare cutaneous diseases reported in distinct immunocompromised hosts. m. haemophilum is a skin and soft tissue infection, whereas crusted scabies is an infestation of the skin. whereas scabies infestation is readily diagnosed, m. haemophilum infection poses a diagnostic challenge due to its rarity as well as varied clinical and histologic presentations. although both scabies infestation and m. haemophilum have been reported in the literature separately, to our knowledge no previous reports have described these diseases occurring simultaneously in an iatrogenically immunosuppressed patient. we report herein a rare case of concomitant m. haemophilum and scabies infestation in a 38-year-old woman with dermatomyositis on multiple immunosuppressive agents. introduction skin march 2018 volume 2 issue 2 copyright 2018 the national society for cutaneous medicine 151 a 38-year-old woman with history of dermatomyositis presented with erythroderma and a non-healing ulcer on her right hand. her treatment regimen consisted of prednisone 20-60 mg daily, mycophenolate mofetil (mmf) 1500 mg daily, hydroxychloroquine 200 mg twice daily, and methotrexate (mtx) 15 mg weekly for multiple years without control of her disease. she was admitted to an outside hospital six times prior where she was given antibiotics for methicillin-resistant staphylococcus aureus (mrsa) without improvement of her finger ulceration. she complained of severe pain and pruritus of her skin diffusely. the patient’s husband reported recent treatment for scabies of himself and two sons, however, the patient was not treated. initial physical exam demonstrated erythroderma with significant scaling and crusting on the head, neck, trunk, and bilateral upper and lower extremities. excoriated papulovesicles were present, and the right third finger had a fivecentimeter ulceration with purulent exudate (figure 1). she also had white patches on her posterior pharynx and tongue as well as superficial ulcerations on her buttocks without genital involvement. cutaneous sensation was intact, and there was no proximal muscle weakness. laboratory studies demonstrated leukocytosis of 20.46 x 10 9 /l with 30% eosinophils as well as an elevated creactive protein (crp) of 5.84 mg/dl and an elevated erythrocyte sedimentation rate (esr) of 70 mm/hr. initial microbiology studies revealed oropharyngeal candidiasis, herpes simplex virus-2 from a gluteal ulcer, and mrsa from the right hand ulceration. blood cultures were negative. hiv, hepatitis serologies, quantiferon gold, and rapid plasma reagin were negative. rheumatologic workup including rheumatoid factor and autoantibodies were negative (anti-nuclear, double stranded dna, smith, ribonucleoprotein, sjögren's-syndromerelated antigen a and b, histidyl trna synthetase, topoisomerase 1, and centromere). creatine phosphokinase (cpk) was normal and aldolase was mildly elevated. skin biopsies revealed a deep dermal and subcutaneous noncaseating granulomatous dermatitis associated with numerous acid fast bacilli (figure 2). in addition, there was a sarcoptes scabiei mite identified. polymerase chain reaction (pcr) studies for rapid-growing nontuberculous mycobacteria (ntm), m. avium complex, m. tuberculosis, and m. leprae were negative. initial tissue cultures were negative, however, after eight weeks, cultures grew m. haemophilum confirmed by rpob gene sequencing. with the diagnosis of scabies infestation and mycobacterial infection and no evidence of active dermatomyositis, prednisone was slowly tapered. mtx, mmf, and hydroxychloroquine were held upon admission given the acute infection. the patient received multiple doses of oral ivermectin and topical permethrin for scabies infestation with clearance. subcutaneous nodules became apparent, and biopsies of these nodules also revealed m. haemophilum (figure 3). her final antimicrobial regimen was clarithromycin, ciprofloxacin and rifampin, according to culture susceptibilities. at her two month follow up visit, the underlying erythroderma case report skin march 2018 volume 2 issue 2 copyright 2018 the national society for cutaneous medicine 152 had resolved and the nodules remained present, although improved. ivig and plaquenil were initiated to treat her active dermatomyositis. figure 1. confluent erythematous papulovesicles and plaques on the bilateral lower extremities. figure 2. numerous acid-fast bacilli (fite stain, original magnification x400). figure 3. subcutaneous nodules on the bilateral lower extremities. skin march 2018 volume 2 issue 2 copyright 2018 the national society for cutaneous medicine 153 m. haemophilum skin infections most commonly occur in immunocompromised patients.1 there are few reported cases of m. haemophilum cutaneous infection in patients taking immunosuppressive agents other than for post-transplant immunosuppression. we identified 15 cases in the literature. reported cases include patients who were on immunosuppressive medications for systemic lupus erythematous, rheumatoid arthritis, polymyositis, myasthenia gravis, autoimmune cirrhosis, cutaneous vasculitis, sjogren’s disease and crohn’s disease.5-9 clinically, m. haemophilum infection presents as asymptomatic or painful, solitary or disseminated, papules, nodules, and/or ulcers.1,4 histopathological features of m. haemophilum include necrotic granulomas containing granulocytes, lymphocytes, monocytes and multinucleated giant cells.1 cultures are crucial for identification of the correct species and antimicrobial susceptibilities to determine an appropriate treatment. m. haemophilum may take up to eight weeks to grow in culture, requires iron supplemented media, and grows optimally at 30-32c. there is no standardized antibiotic regimen for m. haemophilum infection. treatment usually includes any combination of clarithromycin, a fluoroquinolone and a rifampicin for 12-24 months.1,9 there have been few reported cases of crusted scabies occurring with lepromatous leprosy. one patient in brazil with a known history of lepromatous leprosy presented with hyperkeratosis and crusted lesions of the hands and feet as well as a disseminated erythematous scaling rash, which was diagnosed by skin scrapings as crusted scabies.10 another case was reported of a 26year-old patient with lepromatous leprosy and widespread crusted scabies infestation.11 additionally, there is a reported case of a disseminated ntm infection with m. kansasii and scabies in a 21-year-old male who was found to have gata2 deficiency.12 although not clearly defined, a defect in cell-mediated immunity may play a role in susceptibility to both atypical mycobacteria infections and infestations with s. scabiei. we report a case of concomitant m. haemophilum and sarcoptes scabiei infestation, and encourage readers to include both diseases in the differential diagnosis of immunocompromised patients presenting with generalized symptomalogy with lesions of different morphologies. conflict of interest disclosures: none. funding: none. corresponding author: divya sadhwani, md department of dermatology & cutaneous surgery university of south florida 12901 bruce b. downs blvd., mdc 79, tampa, fl 813-974-4270 (office) 813-974-4272 (fax) divya.h.sadhwani@gmail.com references: 1. lindeboom ja, bruijnesteijn van coppenraet le, van soolingen d, prins jm, kuijper ej. clinical manifestations, diagnosis, and treatment of mycobacterium haemophilum infections. clin microbiol rev. 2011;24(4):701–17. 2. sampaio jl, alves va, leão sc, et al. mycobacterium haemophilum: emerging or underdiagnosed in brazil?. emerg infect dis. 2002;8(11):1359–60. discussion skin march 2018 volume 2 issue 2 copyright 2018 the national society for cutaneous medicine 154 3. walton sf, beroukas d, robertsthomson p, currie bj. new insights into disease pathogenesis in crusted (norwegian) scabies: the skin immune response in crusted scabies. br j dermatol. 2008;158(6):1247–55. 4. saubolle ma, kiehn te, white mh, rudinsky mf, armstrong d. mycobacterium haemophilum: microbiology and expanding clinical and geographic spectra of disease in humans. clin microbiol rev. 1996;9(4):435–47. 5. lott jp, werth vp, kovarik cl. cutaneous mycobacterium haemophilum infection in iatrogenically immunocompromised patients without transplantation. j am acad dermatol. 2008;59(1):139d–42. 6. teh cl, kong ko, chong ap, badsha h. mycobacterium haemophilum infection in an sle patient on mycophenolate mofetil. lupus. 2002;11(4):249-52. 7. seitz cs, trautemann a, bröcker eb, abele-horn m, goebeler m. skin nodules in rheumatoid arthritis due to infection with mycobacterium haemophilum. . 2008;88(4):428–9. 8. lee wj, kang sm, sung h, et al. nontuberculous mycobacterial infections of the skin: a retrospective study of 29 cases. j dermatol. 2010;37(11):965–72. 9. shah mk, sebti a, kiehn te, massarella sa, sepkowitz ka. mycobacterium haemophilum in immunocompromised patients. clin infect dis. 2001;33(3):330– 7. 10. pedra e cal ap, ferreira cp, da costa nery ja. crusted scabies in a patient with lepromatous leprosy. braz j infect dis. 2016;20(4):399–400. 11. barbosa júnior ade a, silva tm, santos mi, et al. coexistence of an unusual form of scabies and lepromatous leprosy. a case report. pathol res pract. 1996;192(1):88–90. 12. brondfield s, reid m, patel k, ten r, dhaliwal g. disseminated mycobacterial infection and scabies infestation. am j med. 2015;128(10):e41–2. results conclusions • this interim analysis of a prospective, multicenter study confirms the association between gep class and outcomes (p<0.0001). • consistent with prior results, class 1 cases have significantly better recurrence-free, distant-metastasis-free and overall survival compared to class 2 cases (p<0.0001). • in this study, 83% (10 of 12) of patients who developed distant metastases were identified as high risk by the gep test, compared to 50% (6 of 12) who had a sln-positive result indicating that the gep test can improve the identification of high-risk cm patients. • while these results are from an interim analysis of this study cohort, the consistency with prior retrospective and prospective single center studies of the gep test confirms that molecular profiling of melanoma tumors with the 31-gene gep test offers the opportunity for accurate identification of high-risk tumors. • considering the rapid time to event and the accuracy of risk prediction by the gep test, increased surveillance with imaging for class 2 patients may be warranted. references 1. gerami p, et al. clin cancer res. 2015;21:175-83. 2. gerami p, et al. j am acad dermatol. 2015;72:780-5. 3. zager js, et al. j clin oncol 2016;34(suppl; abstr 9581). disclosures funding for this study was provided by castle biosciences, inc., friendswood, tx. interim analysis of survival outcomes in a prospective multicenter cohort evaluating a prognostic 31-gene expression profile (gep) test for melanoma eddy c. hsueh, md1, james r. debloom, md2, jonathan lee, md3, jeffrey j. sussman, md4, craig l. slingluff, jr., md5, kelly m. mcmasters, md, phd6 1st. louis university, st. louis, mo, 2south carolina skin cancer center, greenville, sc, 3northside melanoma & sarcoma specialists of georgia, atlanta, ga, 4university of cincinnati cancer institute, cincinnati, oh, 5emily couric clinical cancer center, university of virginia school of medicine, charlottesville, va, 6james graham brown cancer center, university of louisville school of medicine, louisville, ky acknowledgements the authors acknowledge elizabeth liotta, md (frederick, md), abdallah khourdaji, md, (lodi, ca), charles st. hill, md (las vegas, nv), martin fleming, md (memphis, tn), and adam berger, md (philadelphia, pa) for their contributions to the study. table 1. demographic information for this prospective cohort. figure 2. survival curves for gep groups. rfs, dmfs and os rates, associated 95% confidence intervals (ci) and number of events for class 1 and class 2 groups are shown. median follow-up time was 1.5 years for event-free subjects. background • a prognostic gene expression profile (gep) test that predicts metastatic risk has been previously validated in three studies.1-3 • the test evaluates the expression of 31 genes in primary melanoma tumor to provide a binary classification (low risk class 1 or high risk class 2) of metastasis risk. • to date, 782 cases have been accrued in retrospective cohorts; 26% (201/782) of these are sentinel lymph node (sln) positive. • this study reports the prognostic accuracy of the gep test in an interim analysis of a prospective, multi-center registry cohort. all cases (n=322) class 1 (n=248) class 2 (n=74) p value age, median (range) 58 (18-87) 57 (18-87) 65 (23-85) 0.003 gender female 146 (45%) 123 (50%) 23 (31%) 0.005 male 176 (55%) 125 (50%) 51 (69%) breslow thickness, median (range) 1.2 (0.2-12.0) 1.0 (0.2-7.0) 2.5 (0.4-12.0) <0.001 ulceration absent 238 (74%) 204 (82%) 34 (46%) <0.001 present 58 (18%) 23 (9%) 35 (47%) unknown 26 (8%) 21 (9%) 5 (7%) mitotic rate ≤1/mm2 222 (69%) 176 (71%) 46 (62%) 0.151 >1/mm2 100 (31%) 72 (29%) 28 (38%) node status negative 201 (85%) 155 (89%) 46 (74%) 0.007 positive 36 (15%) 20 (11%) 16 (26%) primary tumor location extremity 178 (55%) 133 (54%) 45 (61%) 0.547 head and neck 58 (18%) 46 (19%) 12 (16%) trunk 86 (27%) 69 (28%) 17 (23%) ajcc stage none 3 (1%) 3 (1%) 0 (0%) <0.001 i 209 (65%) 192 (77%) 17 (23%) ii 73 (23%) 32 (13%) 41 (55%) iii 36 (11%) 20 (8%) 16 (22%) iv 1 (0%) 1 (0%) 0 (0%) table 2. correlation of outcomes with prognostic factors. outcome events (recurrence, distant metastasis or death) in the 322patient prospective cohort and correlation with gep class, sln status, and ulceration. figure 3. kaplan-meier survival analysis to compare prospective and retrospective cohorts. class 1 (blue) and class 2 (red) rfs rates from the prospective (solid lines; n=322) and retrospective (dashed lines; n=782) studies of the gep test. gep class is a significant predictor of rfs in both cohorts. note: 11% (36 of 322) of the cases in the prospective cohort were sentinel lymph node positive, compared to 26% (201/782) of the cases in the retrospective cohort. rfs hr (95% ci) p value mitotic rate 1.05 (1.01-1.08) 0.005 ulceration present 1.89 (0.75-4.72) 0.17 breslow thickness 1.43 (1.18-1.73) 0.001 sln positivity 2.46 (1.07-5.68) 0.035 gep class 2 7.15 (1.99-25.8) 0.003 table 3. cox regression analysis for recurrence of disease. hazard ratios (hr) for each clinical factor considered in the cox multivariate analysis are shown with 95% confidence intervals (ci). breslow thickness, mitotic rate, and gep class were considered significant. 296 complete cases were used in these analyses. methods • eleven u.s. dermatologic and surgical centers participated in two irbapproved registry protocols. physicians enrolled cm pts who were ≥16 years old and had successful gep test results. • endpoints of recurrence-free (rfs), distant metastasis-free (dmfs) and overall survival (os) were assessed using kaplan-meier and cox regression analysis. • as an interim analysis at year 3 of an expected 5-year study, the critical alpha level (p value) was 0.01. limitations a limitation of the study is the median follow-up time of 1.5 years. however, prior studies have shown that the gep test identifies tumors at high risk for near-term metastasis (e.g., median time to recurrence for class 2 cases is 1.1 years). thus, this interim analysis is based on greater than 50% of events that are expected in this cohort, the majority of which occur in the class 2 population. rfs n (rate of recurrences) dmfs n (rate of dm) os n (rate of deaths) class 1 (n=248) 5 (2%) 2 (0.4%) 3 (1%) class 2 (n=74) 20 (27%) 10 (14%) 8 (11%) p-value <0.0001 <0.0001 <0.001 sln(n=286) 15 (5%) 6 (2%) 10 (3%) sln+ (n=36) 10 (28%) 6 (17%) 1 (3%) p-value <0.0001 <0.001 1 ulceration(n=264) 10 (4%) 3 (1%) 6 (2%) ulceration+ (n=58) 15 (26%) 9 (16%) 5 (9%) p-value <0.0001 <0.0001 0.04 rfs figure 1. schematic of the gep test workflow fc17postercastlebioscienceshsuehinterimanalysismelanoma.pdf powerpoint presentation figure 1: study flow diagram poster presented at the 2018 winter clinical dermatology conference in maui, hi; january 12-17th, 2018. real world experience with calcipotriene and betamethasone dipropionate foam 0.005%/0.064% (cal/bd foam) in the treatment of adult psoriasis itch from retrospective chart review jashin j. wu, md1; karen a. veverka, phd2; minyi lu phd2; and april w. armstrong, md3 1department of dermatology, kaiser permanente los angeles medical center, los angeles, ca; 2leo pharma inc., madison, nj; 3department of dermatology, keck school of medicine of university of southern california, los angeles, ca, usa. introduction results conclusions materials & methods disclosures references  despite a reported global prevalence of pruritus ranging from 64% to 97%1, the real-world data on the impact of topical medications on itch in psoriasis patients has not been widely reported.  treatment with the foam formulation of calcipotriene 0.005%/betamethasone dipropionate 0.064% (cal/bd) foam is a topical treatment for chronic adult plaque psoriasis with efficacy and safety established in clinical trials.2-5  we assessed the clinical characteristics, treatment patterns, and other physician and patient characteristics, adverse events, and resource utilizations in patients using cal/bd foam to treat plaque psoriasis.  the results of our study uniquely provide real-world practice data for topical psoriasis therapy with cal/bd foam including impact on itch. study design  retrospective, observational, medical chart review conducted at clinical practice sites in us  psoriasis vulgaris (n=105) patients ≥18 years who initiated cal/bd foam between jan 1, 2016 and oct 31, 2016 were included.  patients were required to have baseline visit and at least 3 months of available data after treatment initiation, and no history of psoriatic arthritis.  hcps who abstracted records reported being experienced in treating psoriasis and in prescribing cal/bd foam, and were balanced for geographical representation. (figure 1)  the healthcare providers were asked to complete a survey to assess attitudes towards cal/bd foam. table 1. patient baseline demographics patient demographics  59 men and 46 women; mean age at cal/bd foam initiation 41.7 years (table 1)  most of the patients are white (88%); 9% of hispanic ethnicity  60% patients diagnosed with psoriasis before cal/bd foam initiation  91.4% with ≥1 follow-up visit after cal/bd foam initiation baseline disease characteristics  patients had a history of plaques affecting knees, n=45 (43%); elbows n=39 (37%); trunk n=30 (29%), lower extremities n=27 (26%), scalp n=24 (22%), and upper extremities n=20 (19%). (table 2)  the median bsa plus scalp was 5.0% and ranged from 1%-85%. (figure 2)  45.7% of patients complained of itch and itch affected the quality of life of 60.4% of the patients who experienced itch at baseline. (table 3)  clinical measures of disease severity (e.g., pga, pasi) were not recorded in patient charts and therefore were not available.  itch is present for an overwhelming majority of mildmoderate patients before initiation of topical treatment.  itch is a bothersome symptom; 55.2% of patients complained about itch to their provider as was documented in their medical chart, and itch affected quality of life for 60.4% of the patients who complained about itch.  based on this chart review study, adult psoriasis patients treated topically with cal/bd foam for up to 4 weeks realized significant improvements in treatment response of plaque lesions. lesions were ‘clear’ or ‘almost clear’ and with important corresponding reductions of itch.  these data help extend results reported from clinical trials with cal/bd foam. table 5. response of itch to cal/bd foam treatment response: pruritus  treatment response was also reported for itch. of the plaques for which the presence of itch was recorded at baseline and time of best response to treatment with cal/bd foam (table 5): o 50% of treated areas (n=6+58) had itch at baseline and 50% did not (n=64) o itch resolved for 90.1% (58/64) of plaques with itch at baseline (i.e., no itch after treatment with cal/bd foam) o all areas (100%) with no itch at baseline did not have itch after treatment. safety and tolerability  adverse events (skin irritation on the knees and the palms/soles) were reported in n = 1/105 (1%) patients in this real-world study. 1. reich a, szepietowski jc. clinical aspects of itch: psoriasis. in: carstens e, akiyama t, editors. itch: mechanisms and treatment. boca raton (fl): crc press/taylor & francis; 2014. chapter 4. available from: https://www.ncbi.nlm.nih.gov/books/nbk200930/ 2. paul c et al. j eur acad dermatol venereol. 2017 jan;31(1):119-126. 3. lebwohl m et al. j clin aesthet dermatol. 2016; 9(2): 34-41. 4. koo j et al. j dermatol treat, 2016; 27(2):120-127. 5. leonardi c et al. j drugs dermatol. 2015; 14(12):1468-1477. • wu jj and armstrong aw have been advisors with/without funding to leo pharma, inc. • lu m and veverka k are employed by leo pharma, inc. • the analysis of data was conducted by rti, inc. and a+a, sponsored solely by leo pharma, inc. • editorial support provided by dharm patel, phd at leo pharma, inc. patients (n=105) n (%) age, years 41.7 sex female male 46 (44%) 59 (56%) race white black asian american indian or alaska native native hawaiian or other pacific islander other ethnicity hispanic 92 (88%) 2 (2%) 5 (5%) 0 (0%) 1 (1%) 5 (5%) 9 (9%) patients (n=105) n (%) history of plaques affecting: scalp facial seborrheic trunk upper extremities (excluded: elbows) elbows lower extremities knees genitals palms/soles nails 24 (22%) 5 (5%) 30 (29%) 20 (19%) 39 (37%) 27 (26%) 45 (43%) 3 (3%) 5 (5%) 4 (4%) table 2. baseline disease characteristics patients (n=105) n (%) bsa, % 5 (1-85) pga not recorded pasi not recorded itch 87 (82.6%) complained of itch 48 (55.2) table 3. baseline disease characteristics figure 2. distribution of bsa plus scalp affected at cal/bd foam initiation treatment response: plaque areas  there were a total of 177 plaque areas treated with cal/bd foam in the study.  cal/bd foam was prescribed to use once-daily (n=124/177 treated plaques; 70.1%) for 4 weeks (n=69/177 treated plaques; 39.0%).  126/177 plaque areas were evaluated for which response could be attributed to cal/bd foam, and of those, 113 were mild-moderate-severe before treatment initiation. (table 4)  after treatment with cal/bd foam:  70.6% of plaques classified as mild/moderate/severe at baseline were ‘clear’ or ‘almost clear’.  55.7% of plaques classified as mild/moderate/severe at baseline were ‘clear’ or ‘almost clear’ with 2-grade improvement. plaque areas (n = 177) # plaque areas evaluated with response to cal/bd foam 126 # plaque areas at mild-mod-sev 113/126 # plaque areas at mild-mod-sev that were ‘clear’ or ‘almost clear’ at time of best response 80 # plaque areas at mild-mod-sev that were ‘clear’ or ‘almost clear’ at time of best response with 2 grade improvement 63 table 4. response of plaques to cal/bd foam plaque areas (n=177) response to cal/bd foam (n) 128 itch (n), prior to cal/bd foam treatment 64/128 no itch (n), prior to cal/bd foam treatment 64/128 itch resolved (n), after cal/bd foam treatment 58 itch not resolved (n), after cal/bd foam treatment 6 n = # plaque areas https://www.ncbi.nlm.nih.gov/books/nbk200930/ slide number 1 figure 2. obs clinical grading improvements in ashen appearance and dry skin parameters figure 3. obs improved ashen appearance, dryness, flaking, tactile roughness and radiance after 2 weeks of daily use figure 4. obs and aho significantly improved dryness, scaling, cracking, and roughness figure 5. comparison of daily obs and aho for treatment of dry heel skin demonstrated comparable efficacy introduction results results conclusions conclusions methods methods objective objective (obs) on large areas of dry, ashen skin of women with darker skin complexions skin on heels compared to aquaphor healing ointment (aho) at week 1 (p<0.05) and week 2 (p<0.001) compared with baseline and compared with untreated legs (p<0.05) (figure 1) parameters for both obs and aho at days 5, 10, and 15 compared to baseline (p<0.001) (figure 4) (figure 5) such as the lower legs skin on the heels, and were not statistically different subjects study design assignment) for 2 weeks assessments subjects study design the other once daily for 15 days assessments tm weber,1 ce arrowitz,1 li jiang,2 k qian,2 a filbry3 1beiersdorf inc., wilton, ct, usa; 2thomas j. stephens & associates, richardson, tx, usa; 3beiersdorf ag, hamburg, germany efficacy of an ointment body spray to improve the appearance of dry, ashy skin and alleviate moderate to severe dryness on the heel figure 1. obs significantly improved skin hydration of dry skin compared with baseline and untreated skin 19.6 23.5 24.9 20.4 20.1 21.1 10 12 14 16 18 20 22 24 26 28 30 baseline wk 1 wk 2 treated untreated n=31 c o rn eo m et er u n it s skin hydration a,c b,c obs=ointment body spray ap<0.05 vs baseline bp<0.001 vs baseline cp<0.05 vs control 5.7 4.3 3.4 5.8 5.8 5.8 0.0 1.0 2.0 3.0 4.0 5.0 6.0 7.0 baseline week 1 week 2 0.0 1.0 2.0 3.0 4.0 5.0 6.0 7.0 baseline week 1 week 2 0.0 1.0 2.0 3.0 4.0 5.0 6.0 7.0 baseline week 1 week 2 ashen appearance m ea n c lin ic al g ra d in g s co re s a,b a,b a,b a,b 5.7 4.8 4.1 5.7 5.9 5.9 a,b a,b dryness 5.5 4.1 3.1 5.5 5.6 5.6 flaking n=31 ap<0.001 vs baseline bp<0.001 vs control treated untreated 0 1 2 3 4 5 6 7 baseline day 5 day 10 day 15 baseline day 5 day 10 day 15 baseline day 5 day 10 day 15 baseline day 5 day 10 day 15 m ea n c lin ic al g ra d in g s co re 0 1 2 3 4 5 6 7 scaling dryness cracking 0 1 2 3 4 5 6 7 0 1 2 3 4 5 6 7 obs aho a a a a a a a a a a a a a a a a a a a a a a a a roughness n=18ap=0.001 vs baseline aquaphor healing ointment’s (aho) efficacy in reducing moderately to severely dry skin is well established. however, application of ointments on large areas can be messy and challenging. ointment body spray (obs) was developed to enable the delivery two clinical studies were conducted to evaluate the efficacy of obs. study a study b untreated: baseline untreated: baseline treated: baseline treated: baseline untreated: week 2 – no change untreated: week 2 – no change treated: week 2 – clinical improvement treated: week 2 – clinical improvement baseline day 15 obs obsaho aho all parameters compared with baseline and untreated legs at week 1 and week 2 (p<0.001) (figure 2, tactile roughness and radiance data not shown) fc17posterbeiersdorfweberefficacyointmentheel.pdf hilary baldwin,1 james del rosso,2 leon kircik,3 linda stein gold,4 adelaide hebert,5 evan a rieder,6 andrew f. alexis,7 julie c. harper,8 richard g. fried,9 siva narayanan,10 volker koscielny,11 ismail kasujee,11 emmy graber12 1acne treatment and research center, brooklyn, ny; 2jdr dermatology research/thomas dermatology, las vegas, nv; 3icahn school of medicine, mount sinai, new york, ny; 4henry ford health system, bloomfield, mi; 5uthealth mcgovern medical school, houston, tx; 6new york university grossman school of medicine, new york, ny; 7weill cornell medical college, new york, ny; 8the dermatology and skin care center of birmingham, birmingham, al; 9yardley dermatology associates, yardley, pa; 10avant health llc, bethesda, md; 11almirall sa, barcelona, spain; 12the dermatology institute of boston and northeastern university, boston, ma. investigator global assessment (iga) of acne vulgaris and iga success among patients with moderate to severe non-nodular acne vulgaris (av) administered sarecycline in community practices across the u.s in proses study: analysis by concomitant medication use introduction: objective of the analysis was to evaluate facial iga and the associated iga success, stratified by the use of concomitant acne medications, among av patients administered sarecycline in community practices across the u.s. methods: a single-arm, prospective cohort study (proses) was conducted with moderate-to-severe nonnodular av patients >9 years who were prescribed sarecycline in real-world community practices in the us. facial iga of av status was collected on a five-point adjectival response scale (0(clear)-4(severe)). iga success at week-12 was defined as >2-grade improvement and score 0-clear or 1almost clear at week-12. proportion of patients achieving iga success was analyzed, stratified by the use of any concomitant av medication during the study (yes vs. no (monotherapy)). results: a total of 253 av patients completed the study. half of the patients (49.80%) were on sarecycline monotherapy (i.e., did not use any concomitant treatments for av). for the overall study cohort, iga success at week-12 was 58.89%. at week-12, iga success was 59.84% among patients using concomitant av medications, and 57.94% among patients using no concomitant av medications (i.e., on sarecycline monotherapy). conclusion: within the study cohort administered sarecycline, a narrowspectrum, tetracycline-derived antibiotic, for 12 weeks, majority of patients achieved iga success at week-12, and the outcomes were similar among patients on sarecycline monotherapy and those on concomitant av medications. synopsis conclusions • within the study cohort administered sarecycline, a narrow-spectrum, tetracycline-derived antibiotic, for 12 weeks, majority of patients achieved iga success at week-12, and the outcomes were similar among patients on sarecycline monotherapy and those on concomitant av medications. sponsored by almirall, s.a. methods • a single-arm, prospective cohort study (proses) was conducted with moderate-to-severe non-nodular av patients >9 years who were prescribed sarecycline in real-world community practices in the us. • a total of 300 subjects were enrolled from 30 community practices across the u.s. • patients and clinicians completed surveys and clinical assessments at baseline and weeks 4, 8 & 12. concomitant medication use was collected at baseline and week-12. • facial iga of av status was collected on a five-point adjectival response scale (0(clear)-4(severe)). iga success at week-12 was defined as >2-grade improvement and score 0-clear or 1-almost clear at week-12. • last observation carried forward (locf) imputation was considered for imputing missing data for the calculation of iga and iga success; however, there was no missing data at week-12, within the analytic population. • proportion of patients achieving iga success was analyzed, stratified by the use of any concomitant av medication during the study (yes vs. no (monotherapy)). objective • the objective of this analysis was to evaluate facial iga and the associated iga success, stratified by the use of concomitant acne medications, among av patients administered sarecycline in community practices across the u.s. results table 1: patient demographics (n=253) demographic group proportion of patients age group, % pediatric (<18 yrs) 39.92 adult (≥18 yrs) 60.08 age group, mean pediatric (<18 yrs) 26.63 adult (≥18 yrs) 14.81 gender, % male 33.60 female 66.40 race,% white 66.80 other 15.81 black/african american 9.88 asian 5.93 prefer not to answer 3.16 american indian or alaskan 0.79 native hawaiian/pacific islander 0.40 ethnicity,% (hispanic, latino or of spanish origin) yes 33.99 no 66.01 baseline iga, % moderate 86.56 severe 13.44 table 2: concomitant medication use (n=253) medication class n (%) has not used any acne medication 126 (49.80) topical medication topical retinoids 62 (24.51) salicylic acid 3 (1.19) benzoyl peroxide 15 (5.93) topical antibiotics 34 (13.44) topical dapsone 13 (5.14) azelaic acid 7 (2.77) topical clascoterone 2 (0.79) other* 43 (17.00) oral medication^ 12 (4.74) • a total of 253 av patients completed the study, demographics shown in table 1. • key concomitant treatments for av observed during the study included: topical retinoids, topical antibiotics, benzoyl peroxide, topical dapsone, and adapalene/benzoyl peroxide. • for the overall study cohort, iga success at week-12 was 58.89%. • there was no statistically significant difference between the facial iga of the group of patients on concomitant av treatments and those patients only on sarecycline monotherapy (figure 2). *28 patients were on adapalene/benzoyl peroxide among others; ^11 were on spironolactone 0.00% 9.09% 33.99% 58.89% 0.00% 10.00% 20.00% 30.00% 40.00% 50.00% 60.00% baseline week 4 week 8 week 12 % p at ie nt s w ith ig a s uc ce ss : c le ar /a lm os t c le ar figure 1: proportion of patients with a facial iga of “clear/almost clear” significantly increased over 12-week study period. all patients (n=253) p<.0001 p<.0001 p-values for 4,8,12 refers statistical significance of change from baseline. 0% 11.02% 38.58% 59.84% 0% 7.14% 29.37% 57.94% 0% 10% 20% 30% 40% 50% 60% baseline week 4 week 8 week 12 % p at ie nt s w ith ig a s uc ce ss : c le ar /a lm os t c le ar figure 2: facial iga success did not differ significantly between the concomitant av treatment group and the monotherapy group patients on concomitant av treatments (n=127) patients on monotherapy (n=126) iga success p>0.05 p>0.05 p>0.05 results p<.0001 skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 523 original research a 35-gene expression profile test for use in suspicious pigmented lesions impacts clinical management decisions of dermatopathologists and dermatologists aaron s. farberg, md1, kelli l. ahmed, phd2, christine n. bailey, mph2, brooke h. russell, phd2, kelly douglas2, clare johnson, rn2, olga zolochevska, phd2, robert w. cook, phd2, matthew s. goldberg, md2,3 1baylor university medical center, dallas, tx 2castle biosciences, inc., friendswood, tx 3icahn school of medicine at mount sinai, ny abstract purpose: histopathological examination is sufficient for diagnosis of many melanocytic neoplasms, however, diagnostic discordance is common between dermatopathologists. a timely and confident diagnosis is optimal, especially in cases where both benign and malignant melanocytic neoplasms are considered in the differential diagnosis as treatment plans diverge significantly. a 35-gene expression profile (gep) test that classifies melanocytic lesions into categories (benign, intermediate-risk and malignant), has reported accuracy metrics of 99.1% sensitivity, 94.3% specificity, 93.6% positive predictive value and 99.2% negative predictive value in a validation cohort of 503 samples. the clinical utility of the 35-gep is described. methods: dermatopathologists (n=6) and dermatologists (n=14) were queried regarding diagnostic challenges and patient management strategies in 60 difficult-to-diagnose melanocytic neoplasms. participants reviewed each lesion twice, once without the 35-gep result and once with. responses were evaluated for consistent trends in the utilization of the 35-gep test result. results: dermatopathologists utilized the 35-gep result to refine their diagnoses in lesions receiving a benign vs. malignant 35-gep result (82.3% diagnostic downgrade vs. 94.9% diagnostic upgrade, respectively). overall, diagnostic confidence was increased (51%), while additional work-up requests were decreased in cases with benign 35-gep (72.1%) and increased with malignant 35-gep (45.6%) results. dermatologists utilized the 35-gep result to gauge overall prognosis which was increased in 76.2% of responses for cases with a benign 35-gep result and decreased in 94.2% of cases with malignant 35-gep result. case difficulty was increased in 54% of responses with a malignant 35-gep result and decreased in 25% if a benign 35-gep result was provided. alterations in office visit frequency (25.9% increase in benign vs. 95.2% increase in malignant 35-gep result) and re-excisions (76.7% decrease in re-excision in benign vs. 44.5% increase in re-excision in malignant 35-gep result) were also influenced by the 35-gep result. conclusions: the diagnosis of challenging melanocytic neoplasms and subsequent clinical management decisions are influenced by 35-gep results in a manner that agrees with the test result. the utility of the test provides the opportunity to improve patient care. skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 524 diagnostic discordance is common in the histopathologic assessment of melanocytic neoplasms.1–5 the accurate diagnosis of suspicious pigmented lesions is vital for appropriate patient care as clinical management decisions are divergent for benign and malignant melanocytic neoplasms; the diagnosis of a malignant melanocytic neoplasm at an early stage of disease is paramount to ensure the best prognosis.6,7 the determination of benign and malignant melanocytic neoplasms remains challenging and routinely involves the histopathological assessment of hematoxylin and eosin (h&e) stained biopsy tissue sections by a dermatopathologist. this h&e evaluation includes subjective pattern recognition that is honed by pathologist experience and is informed by partially quantifiable visual measures of lesion architecture, cytologic atypia, mitotic activity, growth patterns, and background features such as solar elastosis.8 although diagnostic accuracy and confidence are often improved by second opinions and ancillary tests such as immunohistochemistry (ihc), fluorescence in situ hybridization (fish), comparative genomic hybridization (cgh), and gene expression profiling (gep) tests,9–13 diagnostic uncertainty is not entirely eliminated with current testing available to diagnosticians.1 a 23-gep is an ancillary diagnostic gep test that differentiates difficult-to-diagnose lesions as benign or malignant. validation accuracy metrics of the 23-gep are reported as sensitivity of 91.5-94.0% and specificity of 90.0-92.5% in lesions with full diagnostic concordance.14,15 accuracy metrics are calculated after exclusion of lesions classified by 23-gep as indeterminate (2.9-16.2%).14,16–20 despite limitations, the clinical utility of 23-gep has been demonstrated and in general, treatment plans were changed when a malignant 23-gep test result was received.19,20 among 218 difficult-todiagnose lesions, 49.1% of the lesions had a treatment recommendation change.19 23gep utility was also demonstrated through a reduction of lesion re-excisions (48.9% reduction).20 recently, a 35-gep test was developed and validated in an independent cohort (n=503) as an ancillary test to aid in the classification of melanocytic neoplasms into benign, intermediate-risk and malignant groups.21 the 35-gep demonstrated high accuracy metrics: 99.1% sensitivity, 94.3% specificity, 93.6% positive predictive value (ppv) and 99.2% negative predictive value (npv); an intermediate-risk zone was 3.6%. here we evaluate the clinical utility of the 35-gep by assessing diagnoses and patient treatment plans before and after a 35-gep result was provided to dermatopathologists and dermatologists. sample acquisition and 35-gep processing archival samples and de-identified clinical data were collected from multiple independent dermatopathology laboratories as an institutional review board (irb)approved study. formalin-fixed, paraffinembedded (ffpe) lesion tissue was collected (5 μm sections) for subsequent h&e diagnosis by 3 to 5 dermatopathologists. based on this review prior to the clinical utility study, sixty difficultto-diagnose lesions from seven centers were selected (figure 1). these cases were diagnostically discordant or were designated as unknown malignant potential (ump) by a majority of reviewers. introduction methods skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 525 figure 1. overall study schematic. *each case was reviewed in round 1 and round 2. 35-gep information for each case was only available in one round. the order of cases and 35-gep information was randomized between reviewers. gep – gene expression profile. ffpe samples were processed as previously described.21 briefly, lesions were prepared for qrt-pcr expression analysis in a central clia-certified, cap-accredited, and new york state department of health permitted laboratory. tumor sections were macrodissected and total rna extracted. cdna was obtained, samples loaded onto a gene card, and run on the quantstudio 12k pcr system. after algorithm processing, samples were classified as benign, intermediate-risk, or malignant. the 35-gep was not clinically available at the time of this study. dermatopathologist clinical utility determination board certified dermatopathologists (n=6) participated in the study. these dermatopathologists regularly evaluate melanocytic lesions as a part of their clinical practice and indicated their willingness to complete the study within indicated time constraints. h&e slides were scanned at 20x with a leica biosystems aperio at2 to obtain electronic images at 4x-40x magnification. a single digital h&e stained whole slide image from each sample was provided and viewed using aperio eslide manager 12.3 and dermatopathologists completed a questionnaire regarding each lesion. all participants reviewed the cases independently and were asked to complete the study session within ~16 hours, allowing participants’ pace to be individualized. all samples were randomized to ensure that ~50% were accompanied with a 35-gep result during the first review session, and the other half contained the 35-gep result during the second review, which took place one week later. dermatopathologists were provided patient age, sex, biopsy location, and the statement, ”the cases you review today were assessed by at least three dermatopathologists and failed to achieve diagnostic concordance. cases were processed with 35-gep and received a benign, intermediate-risk or malignant classification.“ accuracy metrics and a brief description of the 35-gep were provided. skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 526 diagnoses were recorded as benign, malignant, or uncertain malignant potential (ump). dermatopathologists were queried as described in table 1. dermatologist clinical utility determination board certified dermatologists (n=14) participated if they evaluate melanoma patients as part of their clinical practice and indicated willingness to participate in the study within the indicated time constraints. the dermatologists were provided a diagnosis for each case along with patient’s age, sex, biopsy location, and brief summary of a pathology report. as with the dermatopathologists, the lesion order and timing to which gep results were presented was randomized for participants. dermatologists were questioned as described in table 1. statistics and data interpretation data was processed with r software (version 3.6.3) and presented with graphpad prism (version 8.4.3). during the data analysis, diagnostic upgrades were considered benign to ump, ump to malignant or benign to malignant; diagnostic downgrades were considered malignant to ump, ump to benign or malignant to benign. diagnostic concordance of the six reviewers was assessed and a ‘majority rule’ was established for the final case diagnosis. majority rule was established for lesions where 5/6, 4/6, or 3/6 individuals agreed on the diagnosis (i.e. 1 benign, 2 ump, 3 malignant = malignant). cohort descriptions six board certified dermatopathologists from six states and 14 board certified dermatologists (including seven mohs surgeons) from ten states completed the study (table 2). study questions are described (table 1). dermatologists reported that they typically follow treatment recommendations provided by dermatopathologists (80-100%), while 85.7% also include ancillary test results and clinical information in the final determination of the treatment plan. as described in the study methods, sixty diagnostically challenging lesions were chosen for the study (table 3). these lesions were either diagnostically discordant (n=31, 52.7%) or were classified as ump (n=29, 48.3%) after review by 3-5 independent dermatopathologists prior to this study. the samples were classified as benign (66.7%, n=40), malignant (26.7%, n=16) or intermediate-risk (6.6%, n=4) by the 35-gep test. pre-35-gep results the lesions were assessed by dermatopathologists and dermatologists for diagnosis and treatment recommendations without the knowledge of the 35-gep. dermatopathologists indicated that 30.3% of lesions were diagnostically very challenging or challenging, while 40.3% were considered very easy or easy. lesions were analyzed to determine a ‘majority rule’ diagnosis. lesions were diagnosed as benign (60%), malignant (23.3%), or uncertain malignant potential (ump) (10%). four lesions (6.7%) could not be definitively classified due to diagnostic discordance that did not allow for a ‘majority rule’. without a 35-gep result, full diagnostic concordance of all six dermatopathologists within the full cohort was rare at 6.7% (n=4). 25% of the cases only had a ‘majority rule of 3’ (i.e. two benign, one ump, three malignant) indicating the difficulty in achieving concordance in these lesions. dermatopathologists indicated that results skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 527 table 1. 35-gep clinical utility survey questionnaire. dermatopathologists dermatologists survey question selection options survey question selection options on a scale from 010, with 0 being very unsure and 10 being very confident, how confident are you in your diagnosis? 0-10 what is your perception of the patient's prognosis? 1 (poor) 6 (excellent) please rate on the following scale opinion your opinion of the level of diagnostic difficulty of this case. 1 (very easy) 5 (very challenging) what management would you most likely recommend for this lesion? no further treatment necessary, no further treatment necessary if lesion is completely excised, close clinical surveillance of the biopsy site for possible recurrence, excise <5 mm margins (narrow but complete), excise ≥5 mm margins (but <1 cm), wide local excision (excise ≥1 cm), sentinel lymph node sampling, adjuvant therapy, other out of the following factors, please list the three that were most influential in making your recommendations. patient age, gender, anatomic site of lesion, histopathology, previous experience, gep result, other which of the following most closely describes how often you would plan to see this patient for a physical exam over the next year? every month, every 3 months, every 6 months, every 12 months what additional work-up would you perform in order to arrive at a definitive diagnosis? no additional work-up, examination of additional levels, ihc, consultation with other dermatopathologist, clinicopathologic correlation to confirm sample is representative, fish analysis for melanoma, cgh, myriad mypath melanoma would you refer this patient to any of the following? second dermatologist, pigmented lesion specialist at an academic center, mohs surgeon, surgical oncologist, medical oncologist, none, other who would you consult with? close colleague, regional expert, national expert would you increase surveillance for this patient by implementing any of the following? increased frequency of office visits (physical exam), advanced imaging modalities (included by not limited to dermoscopy, confocal microscopy, oct, total body photography, nevisense), decreased biopsy threshold for future lesions, other, none skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 528 additional information such as ihc would be useful for all lesions. dermatologists were optimistic in overall patient prognosis indicating an excellent prognosis ~85% of the time; however, only ~38% indicated that the cases were easy or very easy to manage. post-35-gep diagnostic results when 35-gep results were provided to dermatopathologists, diagnostic concordance increased among lesions. the number of cases with full concordance increased from 6.7% to 23.3% (n=14). the number of cases achieving a ‘majority rule of 3’ was reduced from 25% to 13.3% following addition of the 35-gep result. the ‘majority rule’ diagnosis was analyzed for each case against the 35-gep result and intra-case diagnostic shifts were observed. when the majority diagnosis was the same as the 35gep result (i.e. benign vs. benign), 69% of cases had an intra-case diagnostic shift towards agreement with the 35-gep (i.e. 4 benign of 6 diagnoses shifts to 5/6 benign diagnoses). when the majority diagnosis table 2. participant demographics dermatopathologists dermatologists age, % (n) 35-49 100 (6) 86 (12) 50-69 14 (2) professional experience (years), n (%) 6-10 64 (9) 11-20 50 (3) 29 (4) 21-30 50 (3) 30+ 7 (1) practice type, n (%) academic 14 (2) community practice 14 (1) private practice 86 (5) 71 (10) other 14 (2) table 3. demographic information for the cases included in this study. clinical utility study cohort n=60 age, median (range) 33 (6-87) gender, % (n) male 48 (29) female 52 (31) location, % (n) acral 3 (2) back 43 (26) chest/abdomen 3 (2) extremities 35 (21) genital 3 (2) head/neck 12 (7) 35-gep result, % (n) benign 66.7 (40) intermediate-risk 6.6 (4) malignant 26.7 (16) growth pattern*, % (n) aimp 2 (1) amp 12 (7) blue nevus 8 (5) combined nevus 5 (3) common nevus 3 (2) compound nevus 3 (2) compound dysplastic nevus 8 (5) deep penetrating nevus 3 (2) dysplastic nevus (not specified) 12 (7) junctional dysplastic nevus 7 (4) lentigo maligna 3 (2) melanoma in situ 3 (2) spitz nevus 23 (14) superficial spreading melanoma 7 (4) * growth pattern was only provided to dermatologists. aimp – atypical intraepidermal melanocytic proliferation, amp – atypical melanocytic proliferation. skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 529 was not the same as the 35-gep result (i.e. ump vs. benign), 79% of cases had an intra-case diagnostic shift to be in more agreement with the 35-gep. when 35-gep results were provided to dermatopathologists, changes in individual diagnoses were observed in 41.7% of cases: diagnostic downgrades were given for 20.3% and diagnostic upgrades were given for 21.4% of responses (figure 2a). as expected, within the 35-gep benign group, 82.3% of observations had downgrades in diagnosis while upgrades were made in 94.9% of 35-gep-malignant results (figure 2b). small numbers of counterintuitive responses were noted (17.8% of 35-gep benign result given a diagnostic upgrade and 5.1% of 35-gep malignant result given a diagnostic downgrade). dermatopathologists’ diagnostic confidence was assessed with the 35-gep result. diagnostic confidence increased in ~51%, had no change in 25%, and decreased in ~24% of responses. diagnostic confidence was more pronounced when lesion diagnosis agreed with the 35-gep result suggesting that the gep result provided a confirmatory confidence in the diagnosis (figure 2b). changes in additional diagnostic work-up were indicated when the 35-gep result was provided; there was a decrease (42.2%), increase (23.3%), and no change (34.4%) (figure 2a). when ranking overall influence on lesion diagnosis, the 35gep result ranked second after histopathology. post-35-gep treatment management results we analyzed dermatologists’ treatment recommendations and overall perception of patient prognosis with the 35-gep results. overall, intended patient management was changed based on the 35-gep result (figure 3a). lesion site surveillance (i.e. a willingness to observe the lesion site or provide no further treatment) was increased for benign lesions in 68.8% of responses, while malignant 35-gep results prompted the dermatologists to decrease surveillance in favor of definitive surgical intervention with 81.8% indicating alignment with management of malignant lesions to provide surgical treatment for those lesions (figure 3b). the lesion excisions (including excision invasiveness trends) were decreased by 76.7% in benign lesions and appropriately remained about the same for malignant lesions (malignant lesions were likely to receive wle [wide local excision] recommendation, see below). moreover, changes in office visit plans and biopsy threshold were observed. a malignant 35gep result would prompt physicians to perform more biopsies for future lesions (79.3%) and more frequent office visits (95.2%), whereas a benign 35-gep result would allow for fewer biopsies (64.2%) and less frequent office visits (74.1%). consistent with standard of care for a malignant melanoma, a malignant 35-gep result prompted an increase in the number of dermatologists’ recommendations for wle (96.4%). overall case difficulty was increased in 54% of responses if a malignant 35-gep result was provided while a benign 35-gep test result decreased case difficulty in 25% of responses. correspondingly, dermatologists’ impression of overall patient prognosis was decreased (e.g. worse prognosis) in 94.2% of responses with a malignant 35-gep test result and increased in 76.2% of responses with benign 35-gep result. the clinical adoption of ancillary gep tests to reduce diagnostic uncertainty were discussion skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 530 figure 2. changes in pre-35-gep and post-35-gep diagnostic decisions made by dermatopathologists. d ia g n o s is c o n fi d e n c e w o rk -u p c o n s u lt e x c is io n w l e 0 50 100 increase decrease no change % o b s e rv a ti o n s d ia g n o s is c o n fi d e n c e w o rk -u p c o n s u lt e x c is io n w l e d ia g n o s is c o n fi d e n c e w o rk -u p c o n s u lt e x c is io n w l e d ia g n o s is c o n fi d e n c e w o rk -u p c o n s u lt e x c is io n w l e -100 -50 0 50 100 benign intermediate-risk malignant in c re a s e , % d e c re a s e , % 35-gep result wle – wide local excision. figure 3. changes in pre-35-gep and post-35-gep diagnostic decisions made by dermatologists. s u rv e y in g l e s io n e x c is io n w l e v is it p la n b io p s y p ro g n o s is 0 50 100 increase decrease no change % o b s e rv a ti o n s s u rv e y in g l e s io n e x c is io n w l e v is it p la n b io p s y p ro g n o s is s u rv e y in g l e s io n e x c is io n w l e v is it p la n b io p s y p ro g n o s is s u rv e y in g l e s io n e x c is io n w l e v is it p la n b io p s y p ro g n o s is -100 -50 0 50 100 benign intermediate-risk malignant in c re a s e , % d e c re a s e , % 35-gep result wle – wide local excision. a. a. b. b. skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 531 pioneered in the fields of thyroid, prostate and lung cancer where multiple tests are commercially available and illustrate the integral role gep information can provide for refining diagnostic certainty and improving patient care.22–25 diagnostic geps for melanocytic neoplasms offer an objective result compared to the subjective interpretation of multiple second opinions and ancillary tests, which are routinely utilized to improve diagnostic accuracy.26 these scenarios result in significant clinical management ambiguity and may necessitate complex conversations with patients regarding treatment and follow-up.27 a novel diagnostic 35-gep has recently been validated. while the head to head comparisons with other gep tests for melanoma diagnosis do not exist, the cross study comparison of accuracy metrics, the substantially reduced intermediate-risk zone, and the inclusion of melanoma in situ lesions in the development and validation of the test position the 35-gep test to provide superior diagnostic clarity when compared to existing geps for melanocytic neoplasms.21 the cohort evaluated for validation of the 35-gep included difficult-to-diagnose lesions reflective of the intended use population (e.g. lesions with ambiguous features upon h&e evaluation). therefore, large shifts in accuracy are not expected in the clinical setting. diagnostic discordance was commonplace in this study’s cohort of melanocytic neoplasms. prior to this study, lesions were assessed by five dermatopathologists and either the majority gave an ump diagnosis or there was no agreement in diagnoses. diagnostic discordance was also prevalent in this study, indicating similar diagnostic styles in the pre-study dermatopathologists and dermatopathologists in this clinical utility study. the diagnostic variance in subtype classification was so substantial that analysis was limited and is not presented herein. the impact of the 35-gep result on diagnosis was demonstrated by the increased intra-case concordance between the six dermatopathologists and by the directionality of the changes when individual diagnoses were observed. diagnostic confidence of dermatopathologists increased whether their diagnosis agreed with the 35-gep or not; however, confidence had a more pronounced increase when the 35-gep confirmed the diagnosis. the decrease in additional work-up requests reflects the increased diagnostic confidence, indicating the dermatopathologist’s certainty in the diagnosis accuracy and that the requirement for additional ancillary testing information is reduced when the 35-gep result is provided. the 35-gep also has an effect on treatment plans. though slnb (sentinel lymph node biopsy) surgical management plans are best suited for surgical oncologists, the dermatopathologists and dermatologists in this study indicated that a malignant 35-gep result would prompt them to recommend wle and slnb procedures more often. in addition, patient office visit recommendations and biopsy thresholds were adjusted in the appropriate direction with the 35-gep result. also, patient prognosis was viewed as more favorable when a benign 35-gep test was included and, conversely, perception of overall prognosis was decreased if a malignant 35gep result was received. the differences in the clinical utility study design and definition of lesion difficulty utilized for the 23-gep and 35-gep makes it difficult to fully extrapolate direct comparisons. the clinical utility of the 23gep has been evaluated and has generally skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 532 demonstrated diagnostic and treatment changes in agreement with the 23-gep test result19,20, despite a high number of challenging lesions receiving an indeterminate result (up to 11% of difficult cases19). the data presented here demonstrates that the 35-gep has similar utility within the difficult lesions presented. only 6.7% of lesions were classified as intermediate-risk by the 35-gep indicating the vast majority of these challenging lesions will be provided with a definitive result. the utility of the 35-gep has been demonstrated and the test can be used to refine the diagnosis of melanocytic neoplasms to provide optimized patient care. the trends for integrating 35-gep test results with clinical management decisions indicate the 35-gep test could benefit clinicians who should derive an increase in diagnostic confidence that leads to greater assuredness in their management plans. with the addition of the 35-gep results patients should receive care that is matched to their diagnosis, and as a result, more appropriate allocation of health care spending could be achieved. conflict of interest disclosures: kla, cnb, bhr, kd, cj, oz, and rwc are employees and shareholders of castle biosciences, inc. msg is an employee of castle biosciences, inc. asf is a consultant to castle biosciences, inc. funding: this study was sponsored by castle biosciences, inc. corresponding author: matthew s. goldberg, md friendswood dr., ste 201 friendswood, tx 77546 phone: 866-788-9007 fax: 866-329-2224 email: mgoldberg@castlebiosciences.com references: 1. elmore jg, barnhill rl, elder de, et al. pathologists’ diagnosis of invasive melanoma and melanocytic proliferations: observer accuracy and reproducibility study. bmj. 2017;357:j2813. doi:10.1136/bmj.j2813 2. farmer er, gonin r, hanna mp. discordance in the histopathologic diagnosis of melanoma and melanocytic nevi between expert pathologists. hum pathol. 1996;27(6):528-531. doi:10.1016/s0046-8177(96)90157-4 3. shoo ba, sagebiel rw, kashani-sabet m. discordance in the histopathologic diagnosis of melanoma at a melanoma referral center. j am acad dermatol. 2010;62(5):751-756. doi:10.1016/j.jaad.2009.09.043 4. glazer a, cockerell c. histopathologic discordance in melanoma can have substantial impacts on patient care. skin j cutan med. 2019;3(2):85. doi:10.25251/skin.3.2.41 5. patrawala s, maley a, greskovich c, et al. discordance of histopathologic parameters in cutaneous melanoma: clinical implications. j am acad dermatol. 2016;74(1):75-80. doi:10.1016/j.jaad.2015.09.008 6. national cancer institute, national institutes of health. melanoma of the skin cancer stat facts. seer. published 2020. accessed october 24, 2019. https://seer.cancer.gov/statfacts/html/melan.htm 7. siegel rl, miller kd, jemal a. cancer statistics, 2018. ca cancer j clin. published online january 4, 2018. doi:10.3322/caac.21442 8. gonzalez ml, young ed, bush j, et al. histopathologic features of melanoma in difficult-to-diagnose lesions: a case-control study. j am acad dermatol. 2017;77(3):543548.e1. doi:10.1016/j.jaad.2017.03.017 9. andea aa. updates on molecular diagnostic assays in melanocytic pathology. diagn histopathol. 2020;26(3):135-142. doi:10.1016/j.mpdhp.2019.12.005 10. lee jj, lian cg. molecular testing for cutaneous melanoma: an update and review. arch pathol lab med. 2019;143(7):811-820. doi:10.5858/arpa.2018-0038-ra 11. miedema j, andea aa. through the looking glass and what you find there: making sense of comparative genomic hybridization and fluorescence in situ hybridization for melanoma diagnosis. mod pathol. published online conclusion mailto:mgoldberg@castlebiosciences.com skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 533 february 17, 2020. doi:10.1038/s41379-0200490-7 12. rimm dl. what brown cannot do for you. nat biotechnol. 2006;24(8):914-916. doi:10.1038/nbt0806-914 13. reimann jdr, salim s, velazquez ef, et al. comparison of melanoma gene expression score with histopathology, fluorescence in situ hybridization, and snp array for the classification of melanocytic neoplasms. mod pathol off j u s can acad pathol inc. 2018;31(11):1733-1743. doi:10.1038/s41379018-0087-6 14. clarke le, flake dd, busam k, et al. an independent validation of a gene expression signature to differentiate malignant melanoma from benign melanocytic nevi. cancer. 2017;123(4):617-628. doi:10.1002/cncr.30385 15. clarke le, warf mb, flake dd, et al. clinical validation of a gene expression signature that differentiates benign nevi from malignant melanoma. j cutan pathol. 2015;42(4):244252. doi:10.1111/cup.12475 16. clarke le, pimentel jd, zalaznick h, wang l, busam kj. gene expression signature as an ancillary method in the diagnosis of desmoplastic melanoma. hum pathol. 2017;70:113-120. doi:10.1016/j.humpath.2017.10.005 17. ko js, matharoo-ball b, billings sd, et al. diagnostic distinction of malignant melanoma and benign nevi by a gene expression signature and correlation to clinical outcomes. cancer epidemiol biomarkers prev. 2017;26(7):1107-1113. doi:10.1158/10559965.epi-16-0958 18. ko js, clarke le, minca ec, brown k, flake dd, billings sd. correlation of melanoma gene expression score with clinical outcomes on a series of melanocytic lesions. hum pathol. 2019;86:213-221. doi:10.1016/j.humpath.2018.12.001 19. cockerell cj, tschen j, evans b, et al. the influence of a gene expression signature on the diagnosis and recommended treatment of melanocytic tumors by dermatopathologists: medicine (baltimore). 2016;95(40):e4887. doi:10.1097/md.0000000000004887 20. cockerell c, tschen j, billings sd, et al. the influence of a gene-expression signature on the treatment of diagnostically challenging melanocytic lesions. pers med. 2017;14(2):123130. doi:10.2217/pme-2016-0097 21. estrada si, shackelton jb, cleaver nj, et al. development and validation of a diagnostic 35gene expression profile test for ambiguous or difficult-to-diagnose suspicious pigmented skin lesions. skin the journal of cutaneous medicine, 4(6), 506-522. https://doi.org/10.25251/skin.4.6.3 22. kristiansen g. markers of clinical utility in the differential diagnosis and prognosis of prostate cancer. mod pathol. 2018;31(s1):s143-155. doi:10.1038/modpathol.2017.168 23. alford av, brito jm, yadav kk, yadav ss, tewari ak, renzulli j. the use of biomarkers in prostate cancer screening and treatment. rev urol. 2017;19(4):221-234. doi:10.3909/riu0772 24. chapman cj, healey gf, murray a, et al. earlycdt®-lung test: improved clinical utility through additional autoantibody assays. tumor biol. 2012;33(5):1319-1326. doi:10.1007/s13277-012-0379-2 25. alexander ek, schorr m, klopper j, et al. multicenter clinical experience with the afirma gene expression classifier. j clin endocrinol metab. 2014;99(1):119-125. doi:10.1210/jc.2013-2482 26. piepkorn mw, longton gm, reisch lm, et al. assessment of second-opinion strategies for diagnoses of cutaneous melanocytic lesions. jama netw open. 2019;2(10):e1912597. doi:10.1001/jamanetworkopen.2019.12597 27. ensslin cj, hibler bp, lee eh, nehal ks, busam kj, rossi am. atypical melanocytic proliferations: a review of the literature. dermatol surg off publ am soc dermatol surg al. 2018;44(2):159-174. doi:10.1097/dss.0000000000001367 skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 932 short communication the jak-cytokine interface – a review and update on prospective clinical considerations david hashemi, md, mba1, neal bhatia, md2 1 harvard combined dermatology residency training program, harvard medical school, boston, ma 2 therapeutics clinical research, san diego, ca janus kinases (jaks) are non-receptor tyrosine kinases that work together with signal transducers and activators of transcription (stat) proteins to form the jak/stat pathway. together, this pathway is responsible for mediating a wide range of downstream cytokines and growth factors, and inhibition of various components of this pathway has been a major area of research focus in recent years. each of the major enzymes of the family – which include jak1, jak2, jak3, and tyrosine kinase 2 (tyk2) – or combinations of jaks is responsible for its own set of most strongly-associated inflammatory mediators (figure 1), and inhibition of specific jaks or combination of jaks can therefore also potentially allow for modulation of specific inflammatory factors and their associated conditions. this article will attempt to provide a concise review of the inflammatory factors affected by each jak, and to support clinicians as they engage in the ever-growing body of research around the use of jak inhibitors for potential treatment of these conditions. atopic dermatitis represents one of the most studied, and consequently most targeted, conditions for jak inhibition to date, with three fda approvals of jak inhibitors, two abstract janus kinases (jaks) are non-receptor tyrosine kinases that work together with signal transducers and activators of transcription (stat) proteins to form the jak/stat pathway. together, this pathway is responsible for mediating a wide range of downstream cytokines and growth factors, and inhibition of various components of this pathway has been a major area of research focus in recent years. each of the major enzymes of the family – which include jak1, jak2, jak3, and tyrosine kinase 2 (tyk2) – or combinations of jaks is responsible for its own set of most strongly-associated inflammatory mediators, and inhibition of specific jaks or combination of jaks can therefore also potentially allow for modulation of specific inflammatory factors and their associated conditions. to date, jak inhibitors have particularly been studied in the treatment of atopic dermatitis (felt to be primarily driven by il4, il-13, and il-5), psoriasis (il-12/il-23), alopecia areata (il-2, il-15, and ifn-γ), and vitiligo (il-15 and ifn-γ), given that these factors can all be found downstream of specific jak/stat pathways as shown in figure 1. by providing a concise review of the inflammatory factors affected by each jak, this article aims to support clinicians as they engage in the evergrowing body of research around the use of jak inhibitors for potential treatment of dermatologic conditions. skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 933 figure 1. interactions between various cytokines and jak1-3, tyk2, itk, tec, and btk. systemic and one topical, for treatment of atopic dermatitis between 2021-2022. as shown in figure 1, atopic dermatitis is classically mediated by il-4 and il-13 (downstream of jak1/3 and jak1/2 respectively) and il-5 (downstream of jak2)1. early fda approvals of jak inhibitors for atopic dermatitis have emphasized the role of jak1 inhibition, with topical ruxolitinib inhibiting jak1/2 and oral upadacitinib and abrocitinib more selectively focusing on jak11-2. with a number of selective jak3 inhibitors in the pipeline, specifically focused on vitiligo and alopecia areata, future research may also evaluate whether selective jak3 inhibition is also able to successfully treat atopic dermatitis via its inhibition of il-4 while avoiding the broader set of cytokines and growth factors downstream of jak1. psoriasis is primarily mediated by the il12/il-23 pathway3, which as shown in figure 1 is downstream of jak2/tyk2. through this lens, one can understand why deucravacitinib – a selective tyk2 inhibitor – demonstrates efficacy and has gained fda approval for treatment of psoriasis4, and why less selective jak inhibitors such as tofacitinib (which inhibits jak1/2/3 and was fda-approved for psoriatic arthritis5) demonstrated efficacy as well. however, as shown in figure 1, both tyk2 and jak1/2/3 also act on a very wide range of off-target skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 934 downstream factors, raising the question of whether il-12, il-23, and/or il-17 can be more selectively targeted in future generations of jak inhibitors. alopecia areata is driven by inflammation believed to be mediated by il-2 and il-15 (which is downstream of jak1/3, as shown in figure 1), as well as ifn-γ (downstream of jak1/2)6. the first fda-approved jak inhibitor for alopecia areata was oral baricitinib7, which inhibits jak1/2 and therefore likely impacts all of these factors. vitiligo is also driven by il-15 (downstream of jak1/3) and ifn-γ (downstream of jak1/2)89, and like alopecia areata saw its first fda approved jak inhibitor in the form of a jak1/2 inhibitor (topical ruxolitinib). more recently, there has been increasing research evaluating the potential for more targeted inhibition of jak3 for alopecia areata and vitiligo, given it is still upstream of both il-2 and il-15 with fewer off-target factors than those downstream of jak1/2. interim results for ritlecitinib (a selective jak3 inhibitor) in phase 3 alopecia areata studies10 and phase 2b vitiligo studies11 may potentially support this hypothesis, highlighting the potential promise of targeted inhibition aimed at specific cytokines of interest. in addition to these 4 initial dermatologic conditions for which jak inhibitors have been approved to date, there have been a broad range of additional conditions reported for which jak inhibition may hold promise12. by more specifically understanding which inflammatory mediators are downstream of each specific jak, scientists and clinicians can aim to further optimize targeting of a given condition’s driving mediators, thereby maximizing impact while minimizing off-target effects and thus improving patient outcomes. conflict of interest disclosures: dr. hashemi has completed an externship as entrepreneur in residence at gore range capital. dr. bhatia has served as an advisor, consultant, and investigator for abbvie, almirall, arcutis, arena, beiersdorf, biofrontera, bms, bi, dermavant, galderma, incyte, isdin, j&j, laroche-posay, leo, lilly, novartis, ortho, pfizer, regeneron, sanofi, sunpharma, and verrica. funding: none corresponding author: neal bhatia, md therapeutics clinical research san diego, ca email: bhatiaharbor@gmail.com references: 1. bieber t. atopic dermatitis: an expanding therapeutic pipeline for a complex disease. nat rev drug discov. 2022 jan; 21(1):21-40. 2. nezamololama n, fieldhouse k, metzger k, gooderham m. emerging systemic jak inhibitors in the treatment of atopic dermatitis: a review of abrocitinib, baricitinib, and upadacitinib. drugs context. 2020 nov 16; 9:2020-8-5. 3. hawkes je, yan by, chan tc, krueger jg. discovery of the il-23/il-17 signaling pathway and the treatment of psoriasis. j immunol. 2018 sep 15; 201(6):1605-1613. 4. armstrong aw, gooderham m, warren rb, papp ka, strober b, thaçi d, morita a, szepietowski jc, imafuku s, colston e, throup j, kundu s, schoenfeld s, linaberry m, banerjee s, blauvelt a. deucravacitinib versus placebo and apremilast in moderate to severe plaque psoriasis: efficacy and safety results from the 52-week, randomized, double-blinded, placebo-controlled phase 3 poetyk pso-1 trial. j am acad dermatol. 2023 jan; 88(1):29-39. 5. berekmeri a, mahmood f, wittmann m, helliwell p. tofacitinib for the treatment of psoriasis and psoriatic arthritis. expert rev clin immunol. 2018 sep; 14(9):719-730. 6. lensing m, jabbari a. an overview of jak/stat pathways and jak inhibition in alopecia areata. front immunol. 2022 aug 30; 13:955035. 7. king b, ohyama m, kwon o, zlotogorski a, ko j, mesinkovska na, hordinsky m, dutronc y, wu ws, mccollam j, chiasserini c, yu g, stanley s, holzwarth k, delozier am, sinclair r; braveaa investigators. two phase 3 trials of baricitinib for alopecia areata. n engl j med. 2022 may 5; 386(18):1687-1699. skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 935 8. faraj s, kemp eh, gawkrodger dj. pathoimmunological mechanisms of vitiligo: the role of the innate and adaptive immunities and environmental stress factors. clin exp immunol. 2022 jan 28; 207(1):27-43. 9. richmond jm, strassner jp, zapata l jr, garg m, riding rl, refat ma, fan x, azzolino v, tovar-garza a, tsurushita n, pandya ag, tso jy, harris je. antibody blockade of il-15 signaling has the potential to durably reverse vitiligo. sci transl med. 2018 jul 18; 10(450):eaam7710. 10. tsianakas a. long-term safety and efficacy of ritlecitinib in adults and adolescents with alopecia areata: interim results from the allegro-lt phase 3, open-label trial. d3t01.1g, eadv congress 2022, milan, italy, 7‒10 september. 11. ezzedine k, peeva e, yamaguchi y, cox la, banerjee a, han g, hamzavi i, ganesan ak, picardo m, thaçi d, harris je, bae jm, tsukamoto k, sinclair r, pandya ag, sloan a, yu d, gandhi k, vincent ms, king b. efficacy and safety of oral ritlecitinib for the treatment of active nonsegmental vitiligo: a randomized phase 2b clinical trial. j am acad dermatol. 2023 feb; 88(2):395-403. 12. howell md, kuo fi, smith pa. targeting the janus kinase family in autoimmune skin diseases. front immunol. 2019 oct 9; 10:2342. powerpoint presentation baseline characteristics • in total, 18 subjects (face, n=9; scalp, n=9) were enrolled and completed the study (table 1). • the mean (standard deviation, sd) age of subjects was 66.4 (9.42 [range: 43‒83]) years. • subjects were white, predominantly male (83.3%) with fitzpatrick skin type i‒iii (94.4%) and a mean (sd) baseline ak lesion count of 8.2 (2.43 [range: 6‒14]). • mean (sd) dose applied was 137 (44.9) mg among the combined subject group (~55% of the full dose possible, 250 mg). results regina yavel,1 j. scott overcash,2 jay zhi,3 eva cutler,3 david cutler,3 jane fang,3 1tkl research inc., fair lawn, nj, usa; 2estudysite, la mesa, ca, usa; 3athenex inc., buffalo, ny, usa phase i maximal use pharmacokinetic study of tirbanibulin ointment 1% in subjects with actinic keratosis • the primary objective was to determine the pk of tirbanibulin ointment 1% under maximal use conditions. • secondary objectives were to evaluate the safety and tolerability of tirbanibulin ointment 1% and to determine the pk of tirbanibulin metabolites. objectives • writing support was provided by tfs s.l. • this study was sponsored by athenex, inc.. acknowledgements conclusions • under maximal use conditions, low systemic exposure of tirbanibulin with subnanomolar plasma concentrations for both parent drug and metabolites was confirmed. • tirbanibulin ointment 1% for 5 days was well tolerated for the treatment of ak on the face/balding scalp. methods study design • subjects (aged ≥18 years) with ≥6 clinically typical, visible and discrete ak lesions on 25 cm2 of the face/balding scalp were enrolled in the study. • subjects self-applied sufficient tirbanibulin to cover the treatment area (25 cm2 area of the face/balding scalp) from the 250 mg sachet once-daily for 5 consecutive days. subjects were instructed to avoid touching or wetting the treatment area for at least 12 hours after drug application. study evaluations pharmacokinetics • pk blood sampling (for tirbanibulin and its inactive metabolites [kx2-5036 and kx25163]) occurred on days 1, 3 and 4 at 0 (pre-dose) and on day 5 at 0, 2, 4, 6, 8, 10, 12, 16 and 24 hours post-the day 5 application. safety • adverse events (aes) were assessed. • lsrs (erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, erosion/ulceration; scale of 0‒3 [absent‒severe]) were evaluated on days 1, 6, 8, 15 and 29; and lsr composite scores were calculated as the sum of all individual lsr scores at each visit with the possible range of 0–18. • tirbanibulin is a synthetic, highly selective, novel inhibitor of tubulin polymerisation and src kinase signalling developed as a first-in-class topical formulation for the treatment of actinic keratosis (ak)1. • in phase i/ii studies, tirbanibulin was minimally absorbed and systemic exposure was low when applied topically. • previous phase i and ii studies showed that tirbanibulin ointment 1% for 5 days was effective against ak lesions on the forearm, face and scalp. local skin reactions (lsrs) were mostly transient and mild-to-moderate in severity, and tirbanibulin was well tolerated.2,3 these studies supported the further development of the 5-day clinical regimen of tirbanibulin ointment 1% in treating ak on the face/scalp. • results from two phase iii studies (kx01-ak-003/kx01-ak-004), demonstrated that tirbanibulin ointment 1% self-administered once-daily for 5 days resulted in higher rates of complete lesion clearance at day 57 compared with placebo (kx01-ak-003: 44% vs. 5%, p<0.0001; kx01-ak-004: 54% vs. 13%, p<0.0001) and was well tolerated, potentially making it a valuable new addition to ak treatment4 (see eado 2020 poster #35). • here, we present results from a phase i, open-label, uncontrolled, non-randomised, maximal use pharmacokinetic (pk) study (kx01-ak-007) evaluating the systemic exposure and safety of tirbanibulin ointment 1% (5 days) applied to the face/balding scalp of adults with ak. synopsis safety adverse events • four subjects (face, n=1; scalp, n =3) experienced a total of 5 treatment-emergent aes (teaes); all were unrelated to treatment. • one subject in the scalp-treated group experienced a treatment-related teae (mild skin dryness; resolved spontaneously). • there were no serious aes, severe aes, deaths or teaes leading to study discontinuation. local skin reactions • lsrs on the treatment area were mostly transient, all were mild-to-moderate erythema and flaking/scaling that peaked around day 8 (mean [sd] composite score: 3.4 [1.76]) before resolving or returning to baseline. table 1. subject demographics and baseline characteristics face (n=9) scalp (n=9) combined (n=18) mean age (sd), years 71.1 (6.92) 61.8 (9.58) 66.4 (9.42) gender: female, n (%) 3 (33.3) 0 3 (16.7) male, n (%) 6 (66.7) 9 (100) 15 (83.3) race: white, n (%) 9 (100) 9 (100) 18 (100) ethnicity, n (%) hispanic or latino 0 2 (22.2) 2 (11.1) not hispanic or latino 9 (100) 7 (77.8) 16 (88.9) fitzpatrick skin type,a n (%) i 2 (22.2) 2 (22.2) 4 (22.2) ii 2 (22.2) 2 (22.2) 4 (22.2) iii 5 (55.6) 4 (44.4) 9 (50.0) iv 0 1 (11.1) 1 (5.6) mean (sd) baseline ak lesion count 8.4 (2.46) 7.9 (2.52) 8.2 (2.43) 40th annual fall clinical dermatology conference, october 29 november 1, 2020 figure 1. (a) mean trough plasma concentrations of tirbanibulin at days 1, 3, 4 and 5; (b) individual plasma concentrations of tirbanibulin with overall mean on day 5 postdose atype i: always burns easily, never tans; type ii: always burns easily, tans minimally; type iii: burns moderately, tans gradually; type iv: burns minimally, always tans well. ak, actinic keratosis; sd, standard deviation. pharmacokinetics tirbanibulin • using an lc-ms/ms bioanalytical assay (lower limit of quantification [lloq] of 0.01 ng/ml), all subjects had measurable but low concentrations of tirbanibulin at troughs (figure 1). • by the observed ctrough plateau, the pre-dose concentration ctrough data demonstrated that steady-state was achieved following the third dose (72 hours) of once-daily, 5 days of dosing. • on day 5, mean (sd) cmax was 0.258 (0.231) ng/ml (0.598 nm), median tmax was 6.91 h, and mean (sd) auc0-24h was 4.09 (3.15) ng∙h/ml (table 2). tirbanibulin metabolites • for the majority of subjects, plasma concentrations for the main tirbanibulin metabolites kx2-5036 (n=14/18) and kx2-5163 (n=13/18) were below the lloq of 0.05 ng/ml. references 1. smolinksi, mp, et al. j med chem. 2018;61:4707-4719; 2. dubois j, et al. phase i study of tirbanibulin ointment 1%, a novel src phosphorylation and tubulin polymerization inhibitor, in subjects with actinic keratosis. poster presented at the 6th annual practical symposium, beaver creek, co, usa, august 8–11, 2019; 3. dubois j, et al. phase ii study of tirbanibulin ointment 1%, a novel src phosphorylation and tubulin polymerization inhibitor, for actinic keratosis. poster presented at the 6th annual practical symposium, beaver creek, co, usa, august 8–11, 2019; 4. blauvelt a, et al. tirbanibulin ointment 1% for actinic keratosis(ak): results from two phase 3 studies with 1-year follow-up. poster presented at the maui derm virtual congress, june 24-27, 2020 table 2. tirbanibulin plasma pk parameters following 5 days of consecutive topical dosing face (n=9) scalp (n=9) combined (n=18) mean (sd) cmax (ng/ml) 0.340 (0.297) 0.176 (0.102) 0.258 (0.231) tmax a (h) 6.0 (2.0, 9.8) 7.8 (2.0, 10.0) 6.91 (2.0, 10.0) auc0-24 (h*ng/ml) 5.0 (3.9) 3.18 (1.92) 4.09 (3.15) afor tmax, median (min, max) are reported. auc0-24, area under the curve from 0-24 hours; cmax, maximum plasma concentration; pk, pharmacokinetic; tmax, time of maximum concentration. a b patient tolerability of tazarotene foam, 0.1%, and impact on patient compliance real world patient perceptions of the use of tazarotene 0.1% foam in the treatment of acne vulgaris james q. del rosso do, faocd, faad; 1 corey l. hartman md faad; 2 caitlin lewis phd; 3 rhonda schreiber msrn.4 1. dréno b, thiboutot d, gollnick h, finlay ay, layton a, leyden jj, leutenegger e, perez m; global alliance to improve outcomes in acne. large-scale worldwide observational study of adherence with acne therapy. int j dermatol. 2010 apr;49(4):448-56. 2. kircik lh. importance of vehicles in acne therapy. j drugs dermatol. 2011 jun;10(6):s17-23. 3. del rosso jq, kircik lh, zeichner j, stein gold l.. the clinical relevance and therapeutic benefit of established active ingredients incorporated into advanced foam vehicles: vehicle characteristics can influence and improve patient outcomes. j drugs dermatol. 2019 feb 1;18(2s):s100-s107. 4. eastman wj, malahias s, delconte j, dibenedetti d. assessing attributes of topical vehicles for the treatment of acne, atopic dermatitis, and plaque psoriasis. cutis. 2014 jul;94(1):46-53. 5. smith ja, narahari s2, hill d, feldman sr. tazarotene foam, 0.1%, for the treatment of acne. expert opin drug saf. 2016 jan;15(1):99-103. 6. feldman sr, werner cp, alió saenz ab. the efficacy and tolerability of tazarotene foam, 0.1%, in the treatment of acne vulgaris in 2 multicenter, randomized, vehicle-controlled, double-blind studies. j drugs dermatol. 2013 apr;12(4):438-46. 7. epstein el, stein gold l. safety and efficacy of tazarotene foam for the treatment of acne vulgaris.clin cosmet investig dermatol. 2013 may 14;6:123-5. 8. data on file, mayne pharma. references 1. jdr dermatology research/thomas dermatology, las vegas, nv; touro university, henderson, nv; 2. skin wellness dermatology, birmingham, al; university of alabama birmingham, al; 3. clewy communications, raleigh, nc. 4. mayne pharma, greenville, nc. these surveys and analysis were sponsored by mayne pharma. disclosure total respondents through week 12 n=372 n(%) gender male 118 (31.7) female 252 (67.7) other 2 (0.6) age 12-20 107 (29) 21-30 121 (33) 31+ 143 (38) race caucasian 252 (68) african american 36 (10) hispanic or latino 46 (12) other 37 (10) conclusion in the 12 week survey, participants were asked “overall how satisfied are you with tazarotene 0.1% foam?”. satisfaction rates increased from week 4 to week 12 and of the 371 patients who responded to this question at week 12, 71% stated they were either very satisfied or satisfied with tazarotene 0.1% foam and 69% were satisfied with the clearance of acne achieved during the survey period. while satisfaction was favorable overall the highest levels were reported by the following subsets: female patients, those who used the product on their face only, those who used the product in winter, and those who used the product most consistently. satisfaction increased slightly with age, however the difference between the 3 sub-groups of age was quite low. the same can be seen across the various races who participated in the surveys. while non-white responders reported slightly higher levels of satisfaction, the differences between the sub-groups are also low. while common perception is that foams are suited better to large treatment areas and topical retinoids are poorly tolerated on the face, 77% of participants in these surveys were using tazarotene 0.1% foam on the face and the data showed higher satisfaction levels in those using the product on the face only vs. those using it on the trunk only or face and trunk. when satisfaction was rated based on season of use, tazarotene 0.1% foam again showed results that contradict traditional views that topical retinoids are not well tolerated in the dry winter months. in these satisfaction was very similar regardless of season of use, with participants using the product during the winter months actually rating satisfaction slightly higher. participants who reported using the product daily or every other day on every survey were defined as ‘consistent use’ (n=215). those who marked an option other than daily or every other day use on any survey were defined as ‘some inconsistent use’ (n=156). a subset of the latter group were those who never reported daily or every other day use, defined as ‘only inconsistent use’ (n=61). patients in the ‘consistent use’ group reported slightly greater satisfaction rates, which aligns with expectations that consistent use or adherence to treatment regimen should result in increased satisfaction with treatment outcomes. acne vulgaris (av) is the most common inflammatory skin disorder seen in outpatient dermatology clinics in the united states. both adolescents and adults of all races and genders are frequently affected. in addition to the impact of av on physical appearance, there are several adverse psychosocial consequences that impair quality of life. continued patient compliance with topical therapies is a recognized barrier to optimal treatment of chronic disorders such as av.1 patient satisfaction with a topical vehicle formulation strongly influences adherence with treatment.2-4 tazarotene 0.1% foam is the only retinoid approved for use in a foam vehicle and is well established as an effective, safe, and well tolerated topical treatment for av.5-7 data from the phase iii studies evaluating tazarotene 0.1% foam for av supported positive patient experiences with both therapeutic outcomes and formulation characteristics.8 these overall positive patient experiences from clinical trial patients in a controlled setting prompted a subsequent analysis using a series of surveys administered to current users of tazarotene 0.1% foam to gather perspectives on its use in “real world” clinical practice. patients with av on the face and/or trunk who were being treated with tazarotene 0.1% foam were asked to rate their experiences of using the product over the course of 12 weeks. introduction • around 3000 survey kits were distributed across the usa to capture data from diverse geographical areas and climates • two waves of the survey were administered in order to capture use in the winter months as well as non-winter months • surveys were administered at baseline, weeks 2, 4, 8 and 12 • feedback was gathered on overall patient satisfaction with use of the product, perceived therapeutic impact on av, and topical vehicle preference • after registering at baseline patients completed surveys within 3 days of the 2, 4, 8, and 12 week dates to ensure feedback was gathered at the specific time points • patient responses were gathered and tabulated by a third party vendor to ensure consistency of reporting and objectivity of analysis • a total of 372 patients participated in the surveys through week 12 with a broad range of diversity across gender, age, and race (not all responded to every question; n values = number of respondents to each question in results graphs) methods discussion it is well known that topical vehicle formulation can significantly alter drug delivery and therefore impact safety, efficacy and tolerability.3 in recent years aqueous-based foam formulations have become a preferred vehicle in treating skin disease as their favorable tolerability and cosmetic elegance have led to positive patient preference, increasing the likelihood that adherence to treatment regimens including these foam vehicles will also improve. however, early foam formulations were positioned for use in diseases that affected large body surface areas, leading to a general belief amongst clinicians that the foams were only suitable for large areas, such as the trunk, due to their spreadability.3 in addition, the strength of tazarotene as a topical retinoid, the dryness and irritation commonly associated with early formulations, and lack of familiarity with proper application techniques has also led clinicians to avoid use of tazarotene 0.1% foam on the face and during the dry winter months, regardless of its novel foam formulation and the efficacy shown in phase iii trials. the results of specific questions from the surveys that address these historical perceptions of topical tazarotene and foam formulations were tabulated and can be seen in the graphs to the right. 41 50 55 54 47 45 46 8 41 38 38 38 39 33 40 24 15 11 6 7 8 17 11 25 p e rc e n t o f r e sp o n d e n ts overall product attribute rating (n=371*) excellent good fair 82% 88% 93%92%93% 88% 86% 32% 56% 19% 14% 11% foam cream gel lotion p e rc e n t o f r e sp o n d e n ts treatment formulation rating (n=371*) *371 of the total 372 participants completed this question at week 12 participants were asked to rate a number of qualities of tazarotene 0.1% foam at all time points during the surveys. the product rated very strongly, largely as excellent or good, in all attributes with the exception of moisturizing. however, given that topical retinoids have been historically considered to be drying, a total of 32% of respondents ranking “moisturizing” as excellent or good speaks favorably to the novel tazarotene 0.1% foam vehicle. participants were asked to rank topical vehicles on a scale of 1 to 5, with 1 being the most preferred formulation and 5 being the least preferred. foam vehicle formulations received the highest ranking by far, with 56% of respondents rating it as “most preferred”. this is between 2-5 times greater than the other vehicles, with the next highest being cream at only 19% of subjects rating it “most preferred”. patients were asked to rate their satisfaction with tazarotene 0.1% foam on all surveys. patient satisfaction with the product increased over the course of 12 weeks and dissatisfaction remained very low throughout. at week 12, 71% of respondents indicated they were very satisfied or satisfied with tazarotene 0.1% foam and 67% indicating that they were likely or very likely to continue use of the product while only 6% stated they were unlikely to continue.8 *371 of the total 372 participants completed this question at week 12*n=participants who completed this question at each time point 35 32 26 38 19 36 45 32 39 39 41 39 32 28 32 37 35 34 25 36 37 42 33 44 36 29 35 31 37 41 37 33 35 37 35 37 33 38 p e rc e n t o f r e sp o n d e n ts overall satisfaction week 12 (n=371*) very satisfied satisfied consistency of useseason of uselocation of useraceagegenderwhole cohort 71% 69% 66% 71% 63% 72% 74% 67% 70% 76% 82% 76% 65% 63% 69% 72% 72% 67% 63% *371 of the total 372 participants completed this question at week 12 % at top of bars = total respondents who were very satisfied or satisfied % at top of bars = total respondents who were very satisfied or satisfied % at top of bars = sum of excellent and good % at top of bars = total respondents who ranked each product as most preferred results 9 21 29 35 39 42 40 36 43 26 20 18 6 7 8 9 2 3 2 4 week 2 (n=282) week 4 (n=309) week 8 (n=299) week 12 (n=371) p e rc e n t o f r e sp o n d e n ts satisfaction over course of treatment very satisfied satisfied neutral dissatisfied very dissatisfied 48% 63% 69% 71% participants were permitted to share self taken photos of their progress throughout the patient experience program • 24 year old caucasian male using tazarotene 0.1% foam as monotherapy consistently every other day to treat av on his face, chest, and back • he was using a moisturizer, but provided no details as to the type or order of application • he had tried other “topicals” in the past as well as oral antibiotics • he has visible clearance over the 4 weeks he submitted photos and was “satisfied” at week 8 • 20 year old caucasian female using tazarotene 0.1% foam inconsistently “a couple of times a week” at week 4 and every other day at week 8 in conjunction with oral minocycline to treat av on her face • she has visible clearance over the 4 weeks she submitted photos and was “unsatisfied” at week 4 during the inconsistent use period, but “neutral at week 8 when she was using more consistently the data presented here, captured from patients who had completed 12 weeks of treatment using the novel foam formulation of tazarotene 0.1% foam, represent a significant sample size with diversity across gender, race, and age. these results contradict many prior assertions regarding topical tazarotene products. patient satisfaction levels increased over the treatment period and after 12 weeks of treatment were consistently high across gender, age and race, regardless of the time of year the treatment was used or the area of the body being treated, and were higher with consistent use vs. inconsistent use. overall, these real-world responses support the results of patient questionnaires from the phase iii studies, with tazarotene 0.1% foam being rated by a strong majority of patients as an effective, tolerable, and easy-to-use treatment option for av of the face and body. skin july 2018 volume 2 issue 4 copyright 2018 the national society for cutaneous medicine 207 original research striae cream with regenetrol complex™ demonstrates efficacy on stretch marks: a double-blind, controlled study stephanie moy ba a , lawrence s. moy md b , timothy lesser bs c a ronald reagan medical center b harbor ucla medical center c torrance memorial medical center stretchmarks, or striae, are a common problem that affects many men and women. clinically, stretchmarks are characterized by a thinning of the skin in streaks usually located around the hips, thighs, buttocks, abdomen, and shoulders. the most common developments of stretchmarks occur during third trimester pregnancy (~40%), pubertal growth spurts or rapid weight gain (~30%), active weight training (~30%), and excessive use of topical cortisones. 1,2 stretchmarks from pregnancy are typically on the abdomen, hips, and thighs. rapid growth rate stretchmarks in females occur along the sides of the hips, on the lateral breasts, and along the arms and legs on the extensor surfaces. young men often develop horizontal, deep stretchmarks across the lower back. weight change induced stretchmarks are usually seen around the trunk, the abdomen, and chest. stretchmarks due to weight lifting are commonly around the shoulders and upper chest. abstract this article reviews the efficacy of the first product that is specifically devoted to treating stretchmarks. stretchmarks previously have been considered an untreatable cosmetic problem. striae cream with the regenetrol complex tm was studied in a double-blind controlled format in which the cream applied to one side of the body was compared with the control cream applied to the other side of the body after two months. the results demonstrate that 80% of the patients tested benefited from using the cream and 35% had marked clearing. results could be seen within 4 weeks. the cream was successful for treating the ridging, redness, and whiteness associated with stretchmarks. additionally, older and thicker stretchmarks demonstrated improvement with regenetrol complex tm application. introduction skin july 2018 volume 2 issue 4 copyright 2018 the national society for cutaneous medicine 208 the streaks characteristics of stretchmarks are often erythematous, hypopigmented or hyperpigmented, and ridged. lesions occur commonly in the presence of skin “stretching” and elevated hormone levels. while most of the symptoms are physical, patients with stretchmarks can experience psychological and emotional distress as well. 3 histopathologically, there is a marked thinning of all the skin layers and especially dramatic thinning of collagen fibers and other connective tissue. on electron microscopy, there is a breakdown and friable deterioration of the fibers in the region of the stretchmarks. also, fibroblasts have the decreased amounts of endoplasmic reticulum and mitochondria characteristic of relatively low levels of protein synthetic activity. several articles discuss the use of various treatments as a way to eliminate stretchmarks. some of the more involved procedures use lasers, micro-needles, microscopy, and pulsed light to solve the problem of stretchmarks. we are currently performing follow up studies involving electron microscopy and its efficacy on stretchmark removal. while fractionated microneedle radiofrequencies, lasers, and pulsed magnetic fields seem to be effective, some patients can still experience the continuing presence of stretchmarks after the procedure. 4,5 although these procedures seem promising, many of them can be complex and out of the normal price range for most patients. other less involved procedures generally include the use of dermatological products, but many of them do not effectively remove the streaks seen in stretchmark development. natural remedies and creams are available for use, but many are not recommended for patients who are looking for a complete disappearance of their stretchmarks and further studies must be done on formulations that produce more significant results. 6,7 while there seem to be many procedures available to patients with stretchmarks, many of these options have a limited effect on stretchmarks and a single clearly effective treatment has not yet been found. 8,9 this study investigates the efficacy of using striae cream with the regenetrol complex tm for the treatment of stretchmarks. healthy normal volunteers were recruited in several dermatologic clinic centers for the studies following institutional review board approval. forty patients were gathered who had significant stretch marks on the hips, abdomen, and thighs, which are generally the most common areas for stretchmarks appear. the patients had an average age of 37 years with a range of 16 to 47 years of age. of the 40 patients, 29 had a positive history of stretch marks occurring during or immediately after pregnancy, seven had lesions from puberty growth periods and four had lesions from weight training. patients were instructed to apply the striae cream with regenetrol complex tm to the stretch marks twice per day. application was done by taking a generous amount and rubbing thoroughly into the skin. a control cream was applied to one side of the body and the striae cream was applied to the other side. both the evaluators and the patients were blinded as to which cream was the striae cream and which was the placebo. methods skin july 2018 volume 2 issue 4 copyright 2018 the national society for cutaneous medicine 209 the study lasted for two months, with evaluations at the beginning, after one month, and at the end of the study after two months. the evaluations were separated into different categories. first, the stretch marks were evaluated for specific characteristics, including erythema, hypopigmentation, hyperpigmentation, and ridging. the patients were also evaluated for extent of improvement over the one month and two-month time period. the evaluation was rated by 0--no change, 1--mild change, 2--moderate change, and 3--marked change. as a separate portion of the study, a blinded evaluator examined the skin and was asked to choose the side that had improved based on the initial evaluations. the evaluator’s chosen side was then compared to the actual treatment side versus the control side. the study evaluated the consequences of applying striae cream with regenetrol complex tm to the stretch marks on each patient. a majority of the patients (80%) had some measurable improvement in the appearance of their stretchmarks (figure 1). out of the 40 patients studied over the twomonth period, 45% had mild improvement (18 patients), 25% had moderate improvement (10 patients), and 10% had marked improvement (4 patients). figure 2 demonstrates the improvement in specific characteristics of the stretchmarks. erythema and hypopigmentation improved the most dramatically with a 72% response, hyperpigmentation improved in 56% of the cases, and ridging improved in 44% of the cases. figure 3 shows that the blinded evaluator was able to choose the correct, active cream in 19 out of 20 cases (95%). the product showed positive benefits to all types of stretchmarks, independent of the cause of development. a chi square statistics test was performed to determine the significance of the results for improvements in the following categories: 'overall', 'redness', 'hypopigmentation', 'hyperpigmentation', and 'ridging'. the total chi square values for were 5.154 for the product and 4.818 for the control, both for four degrees of freedom (critical value of 9.488 for p = 0.05). there was no significant difference between improvements seen in any one category, though there were more improvements seen in general from the product side than the control side. a chi squared test was also performed for the product's efficacy with the categories 'no change', 'mild change', 'moderate change', and 'marked changed'. the chi square value for the product was 10.4 for three degrees of freedom (critical value of 9.348 for p = 0.025) compared with the chi square value for the control, which was 71.8 for three degrees of freedom (critical value of 20.515 for p = 0.001). there was a significant difference in the number of patients who categorized their improvements with the product as 'mild change', while there were fewer who observed no change in their stretch marks. the control cream showed a strong and significant difference in the number of patients who saw no change while there were very few patients who observed any improvement in their stretch marks. figures 4, 5, and 6 demonstrate the visual improvements of stretchmarks after 6 weeks using the striae cream with regenetrol complex tm . although some pigmentation remains, the overall appearance of the stretchmarks has significantly diminished. results skin july 2018 volume 2 issue 4 copyright 2018 the national society for cutaneous medicine 210 figure 1. stretchmark cream improvement on patients. subjects (n=40) self-evaluated the improvement of their stretchmarks by categories: no change, mild, moderate, and marked. 8 participants showed no change in their stretchmarks, 18 showed mild changes, 10 showed moderate changes, and 4 showed marked changes. figure 2. improvement in characteristics of stretchmarks. subjects (n=40) self-evaluated the characteristic changes of their stretchmarks, with 80% of subjects having an overall improvement in the quality of their stretchmarks. 72% of subjects saw a decrease in redness of their skin. 72% saw improvements in hypopigmentation. 72% saw improvements in hyperpigmentation. 44% saw a reduction in the amount of ridging of their stretchmarks. skin july 2018 volume 2 issue 4 copyright 2018 the national society for cutaneous medicine 211 figure 3. the number of correct blinded responses on evaluation of treatment of one side of the body with stretch mark cream. evaluations were made by a skin professional. in 19 out of the 20 cases, the physician was successfully able to identify on which side the striae cream was applied. the study demonstrates the efficacy of a new product for treating stretchmarks. 80% of the patients showed an improvement in the appearance of their stretchmarks from use of the cream. although many of the patients had mild to moderate effects, the results were promising because of the short duration of treatment (two months). anecdotally, a number of patients had measurable improvement in two to four weeks and, in addition, many of the patients showed progressive, dramatic improvement with additional weeks of treatment. the improvement of all the stretch mark characteristics from figure 2 points to a specific action on stretch marks that can improve all facets of the lesions. in a very short two-month study, the lesions would be expected to improve most dramatically with respect to their erythema and hypopigmentation. the ridging effect would correlate with the deepest histologic effect and would continue to improve with continued therapy, but in two months would not be expected to be the most notable response. the blinded evaluator response was performed to ensure the quality of the products and to ensure that the control cream was not producing similar results as discussion skin july 2018 volume 2 issue 4 copyright 2018 the national society for cutaneous medicine 212 the active cream. clearly, there is a visual difference that can be seen due to the clinical improvement that regenetrol tm has on the skin. previous studies have initially shown promise with using topical retinoids for stretchmarks. however, a recent study demonstrated that tretinoin 0.025% cream was “ineffective in improving striae distensae in these subjects.” 10 the lack of concensus of tretinoin's efficacy may be due to possible irritant effects that occur with the product's use. 11 other products have been reported in small studies to improve stretch marks. centella asiatica may be effective, but it is a weak sensitizer. it is not clear if this product also works based on an irritant effect. limitations of this study include the small sample size, the narrow age range of participants, and the short duration of followup. regenetrol tm appears to elevate the level of total protein synthesis. preliminary laboratory studies have so far shown the elevated total protein synthesis to be correlated with an increase in collagen and elastin. as demonstrated, the histologic thickness of the epidermis and the dermis was markedly increased as well. the increase in total protein levels may explain the advantage regenetrol tm has over other products tested at this time. as seen from a number of studies, all protein fibers, including keratin, collagen and elastin, were markedly decreased in people with striae distentae. therefore, regenetrol tm may give the most positive structural support for reversing the weakening of protein fibers associated with stretchmarks. although the study did not specifically examine the most responsive patient for regenetrol tm treatment, anecdotal experience has shown that stretchmarks that are both older and newer can respond well; however, more recently developed stretchmark lesions appear to be more responsive. additionally, stretchmarks from pregnancy and weight training appear to respond equally to the product. responses to growth spurts were positive but efficacy was a little less. anatomical areas did not appear to affect the effectiveness of the product. perhaps the use of this product could be further enhanced with the addition of lasers or other forms of treatment. conflict of interest disclosures: the striae cream with regentrol complex tm is manufactured and distributed by dr. lawrence moy, m.d. funding: none corresponding author: stephanie moy, ba address: 1101 n sepulveda blvd manhattan beach, ca 90266 phone: (310) 546-7780 email: moys@alumni.usc.edu references: 1. valente, d., zanella, r., doncatto, l., & padoin, a. (2014). incidence and risk factors of striae distensae following breast augmentation surgery: a cohort study. plos one. 2. otman, haley. "stretch mark science: what happens to your skin when pregnancy gives you a stretch mark?" university of michigan. university of michigan, health system, 17 nov. 2015. web. 12 may 2016. conclusion skin july 2018 volume 2 issue 4 copyright 2018 the national society for cutaneous medicine 213 3. korgavkar, k., & wang, f. (2015). stretch marks during pregnancy: a review of topical prevention. br j dermatol british journal of dermatology,606-615. 4. dover, j., rothaus, k., & gold, m. (2014). evaluation of safety and patient subjective efficacy of using radiofrequency and pulsed magnetic fields for the treatment of striae (stretch marks). j clin aesthet dermatol. 5. ryu, h., kim, s., jung, h., ryoo, y., lee, k., & cho, j. (2013). clinical improvement of striae distensae in korean patients using a combination of fractionated microneedle radiofrequency and fractional carbon dioxide laser. dermatologic surgery. 6. soltanipour, f., delaram, m., taavoni, s., & haghani, h. (2014). the effect of olive oil and the saj® cream in prevention of striae gravidarum: a randomized controlled clinical trial. complementary therapies in medicine,220-225. 7. ud-din, s., d. mcgeorge, and a. bayat. "result filters." national center for biotechnology information. u.s. national library of medicine, 20 oct. 2015. web. 12 jan. 2016. 8. sardana, k. (2014). lasers for treating striae: an emergent need for better evidence. indian j dermatol venereol leprol indian journal of dermatology, venereology, and leprology, 392-392. 9. moore, j., kelsberg, g., & saphranek, s. (2012). clinical inquiry: do any topical agents help prevent or reduce stretch marks? j fam pract. 10. hexsel, d., soirefmann, m., porto, m., schilling-souza, j., siega, c., & dalʼforno, t. (2014). superficial dermabrasion versus topical tretinoin on early striae distensae: a randomized, pilot study. dermatologic surgery,537-544. 11. black, martin m., christina m. ambrosrudolph, libby edwards, and peter j. lynch. "ch 3: physiologic skin changes of pregnancy."obstetric and gynecologic dermatology. london: mosby, 2008. 24. print. skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 410 clinical trial a randomized, parallel group, open label, multicenter study to assess the potential for adrenal suppression and systemic drug absorption following multiple dosing with clobetasol propionate cream (impoyz™), 0.025% versus clobetasol propionate (temovate®) cream, 0.05% in subjects with moderate to severe plaque psoriasis zoe d. draelos md1, joseph f. fowler md2 , raymond cornelison md3 1dermatology consulting services, pllc, high point, nc 2division of dermatology, university of louisville, new castle, ky 3southern plains medical center, chickasha, ok importance: topical corticosteroids continue to play an important role in therapy for individuals with moderate-to-severe psoriasis, particularly in cases where systemic therapy is contraindicated or in which combination topical-systemic therapy is needed to achieve desired results. although super-high-potency corticosteroids such as clobetasol propionate have the potential to produce desired results, side effects related to systemic absorption may limit their clinical utility. objectives: to evaluate the potential of a new, lower-concentration clobetasol propionate cream 0. 025% (impoyz cream, [imp]) to suppress the hypothalamic-pituitary-adrenal (hpa) axis as compared to clobetasol propionate, 0.05% cream (temovate cream, [tmv]) under maximal use conditions in patients with moderate-to-severe plaque psoriasis. to compare the plasma concentrations of clobetasol propionate before and after 2 weeks of topical treatment with either imp cream or tmv cream under maximal use conditions. design, setting, and participants: randomized, multi-center, open-label study conducted across 15 clinical sites in the united states. eligible subjects were males or females, at least 18 years old, with a clinical diagnosis of stable (at least 3 months) plaque-type psoriasis that involved 20% to 50% of the body surface area (bsa). 50 patients with an investigator global assessment (iga) grade of at least 3 (moderate) at baseline were randomized (1:1) to twice daily treatment with either imp cream or tmv cream for 15 consecutive days. main outcomes and measures: primary safety assessments included hypothalamic-pituitary-adrenal axis suppression (as measured by acth stimulation test) and systemic drug absorption (as measured by plasma clobetasol propionate levels drawn at baseline and on day 15 of treatment at 0, 1, 3, and 6 hours after final study product application). secondary safety assessments included serum dheas at days 8 and 15 and local cutaneous adverse events. the primary efficacy assessment was investigator global assessment (iga) score, measured at days 8 and 15 of treatment. results: upon conclusion of the treatment period, the mean serum concentration of clobetasol propionate was significantly lower in the imp cream group vs the tmv group (56.3 vs 152.5 pg/ml, p=0.014). a lower proportion of subjects in the imp group experienced hpa-axis suppression compared to the tmv group, although this did not reach statistical significance (12.5% vs 36.4%, p=0.086). in terms of efficacy, the two treatment groups displayed similar marked improvement in psoriasis severity after 15 days of treatment, with 50% of the subjects in each group having an iga score of 2 (mild) and 16.7% in the imp group and 18.1% in the tmv group having a score of 0 or 1 (none or minimal). conclusions and relevance: subjects with moderate-to-severe plaque psoriasis treated with a 15 day course of imp cream demonstrate lower levels of plasma clobetasol propionate than those treated with tmv, suggesting lower levels of systemic corticosteroid exposure with imp versus those with tmv. additionally, in this sample, topical therapy with imp was associated with a trend towards a lower incidence of hpa axis suppression than tmv without comprising efficacy. trial registration: registered 6 may, 2014. abstract skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 411 topical corticosteroids continue to play an important role in the treatment of moderateto-severe plaque psoriasis.1 the side effects of topical corticosteroids can be both local and systemic and play an important determination in their use.2,3 systemic exposure, which governs the risk of systemic side effects, can be influenced by variables such as steroid potency, the amount of drug applied, or the duration of use.4 although all topical corticosteroids carry a risk of both local and systemic side effects, high-potency topical steroids have higher rates of systemic absorption and thus carry a higher risk of systemic side effects such as hypothalamicpituitary-adrenal (hpa) axis suppression, hypertension, hyperglycemia, and cushing’s syndrome.2,5 thus, a novel formulation of a commonly-prescribed high-potency corticosteroid that offers a lower degree of systemic absorption compared to existing formulations would have significant utility in the treatment of psoriasis, particularly in patients with higher disease severity and greater bsa involvement. to this end, the objectives of this randomized, open-label, multi-center phase ii safety study were: 1) to evaluate the potential of clobetasol propionate 0.025% cream (impoyz [imp] 0.025% cream) to suppress the hpa axis (a systemic side effect) as compared to clobetasol propionate cream 0.05% cream (temovate [tmv] 0.05% cream), when applied twice daily for 15 days under maximal use conditions in subjects with moderateto-severe plaque psoriasis. 2) to compare the plasma concentrations of clobetasol propionate after multiple uses of tmv cream to imp cream under maximal use conditions. study design this study was a randomized, multicenter, multi-dose, comparator-controlled, open label phase ii clinical trial comparing the safety and efficacy of imp cream (clobetasol propionate 0.025%) versus tmv cream (clobetasol propionate 0.05%) in patients with moderate-to-severe plaque psoriasis. subjects with 20-50% bsa involvement (representing those with large bsas and at the greatest risk of systemic side effects) were enrolled across 15 clinical sites in 10 states from may 8, 2014 to august 11, 2015. subjects were randomized (1:1) to treatment to one of two groups: treatment with imp cream or tmv cream. subjects were instructed to apply the treatment to all affected areas with the exception of the face, scalp, groin, axillae, and other intertriginous areas twice daily, for a target dose of 5 to 7 grams per day. chronic medications being used at the time of screening were continued at the discretion of the investigator (with the exception of agents meeting the criteria for study exclusion). subjects were scheduled for study visits at screening, baseline (day 1), day 8, day 15, and day 43 (if needed to confirm recovery of hpa axis suppression). efficacy evaluations were performed on days 8 and 15, whereas safety evaluations were performed on days 8, 15, 28 (if hpa axis suppression was noted on the day 15 visit), and every 28 days thereafter as needed until resolution of hpa axis suppression was noted. the institutional review board at each participating center reviewed and approved methods introduction skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 412 the study protocol, subject recruiting materials, informed consent form, and all other materials provided to potential subjects for enrollment in the study. the study was conducted in accordance with good clinical practice guidelines and the consolidated standards of reporting trials (consort) guidelines for clinical trials. the full protocol for the study can be accessed on clinicaltrials.gov. inclusion and exclusion criteria in order to be deemed eligible for the study, potential subjects had to be 18 years of age or older with a clinical diagnosis of stable (for a minimum duration of 3 months) plaque-type psoriasis involving 20-50% body surface area (bsa), not including the face, scalp, groin, axillae, or other intertriginous areas. furthermore, to meet the criteria for inclusion, potential subjects were required to have a minimum bsa involvement of 20% and to have an investigator’s global assessment (iga) grade of at least 3 (moderate) at the baseline visit, as well as a normal acth stimulation test and normal dheas level at screening. subjects with unstable forms of psoriasis (for example, guttate, erythhrodermic, exfoliative, or pustular) were excluded from the study. subjects deemed to be immunosuppressed or immunocompromised, including those with use of immunosuppressive drugs or systemic psoriasis therapies within 60 days of the baseline visit were deemed ineligible. subjects who had undergone treatment for any cancer with the exception of skin cancer or cervical cancer in situ within 1 year of the baseline visit were excluded. those who had utilized topical psoriasis therapies (including any use of corticosteroids), phototherapy (puva or uvb), or systemic antiinflammatory agents within 30 days of the baseline visit were excluded from the study. subjects with a known history of hpa axis abnormalities were deemed ineligible. further exclusion criteria consisted of use of dhea or dheas-containing products within 30 days of the screening visit, known hypersensitivity to any ingredients of the study or comparator medications, abnormal sleep schedule, previous enrollment in an investigational drug study within 60 days of the baseline visit, inability to comply with study requirements, severe hypertension (sbp > 160 mmhg or dbp > 100 mmhg) at baseline, and pregnancy or current breastfeeding. assessments the primary safety assessments of interest were determination of hpa axis suppression as indicated by the acth stimulation test and the level of systemic exposure as measured by plasma concentrations of clobetasol propionate. the acth stimulation test is the gold standard test for diagnosis of hpa axis suppression. the test measures an individual’s ability to mount an appropriate response to pharmacologic stimulation of the hpa axis.6 subjects exhibiting signs of hpa axis suppression will not be able to produce a surge of endogenous cortisol in response to administration of cosyntropin (exogenous adrenocorticotropic hormone). the acth stimulation test was performed by collecting a 5 ml blood sample from the subject prior to administration of cosyntropin to function as a “control” measurement. the subject was then administered 0.25 mg of iv or im cosyntropin, followed by repeat collection of 5 ml of blood 30 minutes later. a post-stimulation cortisol level below 18 μg/dl indicated an inadequate response to acth stimulation and was taken to be indicative of hpa axis suppression. skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 413 secondary safety assessments included a local cutaneous safety evaluation for atrophy/telangiectasias and a summary of treatment emergent adverse events (teaes). the primary efficacy assessment was investigator’s global assessment (iga). clinical determinations of disease severity using the iga were performed at each visit from screening through the end of treatment (box 1)the iga score is a static assessment of disease severity based on the overall disease severity at the time of the visit.7 the inclusion criteria for the study required a baseline iga of at least 3 (moderate). statistical analysis all statistical analyses were performed using sas version 9.1.3 statistical software (cary, nc). significance testing was performed at an α-level of 0.05% using analysis of variance (anova) for continuous variables and fisher’s exact test for categorical variables. no imputation was made to account for missing safety data. subject demographics eighty-eight subjects were screened for potential inclusion in the study. of these 88 screened subjects, 50 were randomized, 26 to the imp group and 24 to the tmv group. thirty-four of the 38 screen failures were related to the subject not meeting the prespecified inclusion/exclusion criteria, whereas three were related to withdrawal of consent and one subject was lost to follow-up after the screening visit. out of the 26 subjects randomized to the imp group, 2 (7.7%) self-discontinued the medication prior to the completion of the study, compared to 1 (4.2%) in the tmv group. one subject was box 1. investigator’s global assessment of disease severity. score grade definition 0 none • no plaque elevation above normal skin level • may have residual non-erythematous discoloration • no psoriatic scale • no erythema 1 minimal or almost clear no more than: • very slight elevation above normal skin level • faint light pink coloration • occasional very fine scale, partially covering some of the lesions 2 mild no more than: • slight but definite elevation of plaque above normal skin level • light red coloration • fine scale with some lesions partially covered 3 moderate no more than: • definite elevation with rounded or sloped edges to plaque • definite red coloration • somewhat coarse scale with most lesions partially covered 4 severe/ very severe at least one: • marked elevation with hard, sharp edges to plaque • dark red coloration • coarse, thick scale with virtually all lesions mostly covered and a rough surface results skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 414 lost to follow-up in each group. overall, 46 subjects completed the study, 23 (88.5%) in the imp group versus 22 (91.7%) in the tmv group (appendix 1). of note, one subject from the imp group withdrew from the study but had already undergone a safety evaluation beyond the baseline visit, and thus was included in the analysis of safety outcomes. demographic variables were relatively equally distributed between the two treatment groups (table 1). overall, roughly two-thirds of subjects were male. all subjects were white, but 58.7% were of hispanic or latino descent. the age of included subjects ranged from 18 to 75 years of age. percent bsa involvement of psoriatic plaques ranged from 20% to 50%. there were no statistically significant differences in measured demographic variables between the two groups, although mean age (43.5 years in the imp group versus 50.9 years in the tmv group) did approach statistical significance (p = 0.058, table 1). measurement of extent of exposure to treatment product extent of exposure to treatment product was monitored by the number of topical applications. the planned number of applications for the 15 day treatment period was 29 (two applications per day on days 114 plus one application on day 15). the actual mean number of applications was 28.3 in the imp group versus 31.0 in the tmv group (p = 0.200). overall, 19/24 (79.2%) of subjects in the imp group and 21/22 (95.5%) of subjects in the tmv group reached a minimum of 26 applications (p = 0.101). the mean amount of product applied was 107.0 grams in the imp group versus 101.7 grams in the tmv group. table 1: demographic characteristics of subjects included in safety evaluation. imp cream (n = 24) tmv cream (n = 22) overall (n = 46) pvalue gender 0.603a female 7 (29.2%) 8 (36.4%) 15 (32.6%) male 17 (70.8%) 14 (63.6%) 31 (67.4%) ethnicity >0.80a hispanic/latino 14 (58.3%) 13 (59.1%) 27 (58.7%) nonhispanic/latino 10 (41.7%) 9 (40.9%) 19 (41.3%) race white 24 (100%) 22 (100%) 46 (100%) >0.80a age 0.16a 18-39 10 (41.7%) 2 (9.1%) 12 (26.1%) 40-63 13 (54.2%) 16 (72.7%) 29 (63.0%) 64-75 0 (0%) 4 (18.2%) 4 (8.7%) ≥75 1 (4.2%) 0 (0%) 1 (2.2%) age (years) 0.058b mean ± sd 43.5 ± 14.5 50.9 ± 11.2 47.0 ± 13.4 median 44.5 50.0 48.5 min, max 18, 75 24, 71 18, 75 % bsa involvement >0.80b mean ± sd 26.5 ± 8.6 27.0 ± 8.3 26.8 ± 8.4 median 22.5 24.0 23.5 min, max 20, 50 20, 48 20, 50 afisher’s exact test, banova % = percent, ≥ = greater than or equal to, bsa = body surface area table 2: percent reduction in serum dheas concentration (μg/ml). imp cream (n = 23) (%) tmv cream (n = 22) (%) pvalue percent reduction from screening to day 8 mean ± sd 6.8 ± 28.3 19.7 ± 39.7 0.216a median 2.5 24.8 min, max -50.4, 100.0 -105.3, 100.0 percent reduction from screening to day 15 mean ± sd 11.0 ± 27.0 21.6 ± 46.4 0.353a median 16.1 28.4 min, max -48.7, 69.0 -122.7, 100.0 a one-way analysis of variance (anova) sd = standard deviation skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 415 table 3: number and percentage of subjects reporting treatment-emergent adverse events (teaes). imp cream (n = 24) n, (%) tmv cream (n = 22) n, (%) subjects reporting any teaes 6 (25.0%) 11 (50.0%) subjects with teaes possibly, probably, or definitely related to study product 5 (20.8%) 10 (45.5%) table 4: local cutaneous events at day 15 of treatment imp cream (n = 24) n (%) tmv cream (n = 22) n (%) telangiectasia 0 (0.0%) 0 (0.0%) atrophy 0 (0.0%) 0 (0.0%) burning/stinging 1 (4.2%) 1 (4.5%) pain 0 (0.0%) 0 (0.0%) itching 6 (25.0%) 7 (31.8%) safety of imp (clobetasol propionate 0.025%) cream versus tmv (clobetasol propionate 0.05%) cream at day 15 of the study, 3 (12.5%) subjects in the imp group had an abnormal acth stimulation test result (indicative of hpa axis suppression), versus 8 (36.4%) subjects in the tmv group (p=0.086, figure 1). when assessing systemic exposure, the mean plasma concentration representing the average of all post-treatment concentrations was 56.3 pg/ml (95% ci 9.9 pg/ml to 102.7 pg/ml) for imp cream versus 152.5 pg/ml (95% ci 90.0 pg/ml to 214.9 pg/ml) for tmv cream (p=0.014, figure 2). the mean posttreatment plasma concentrations of clobetasol propionate were significantly greater in subjects with hpa axis suppression (determined by abnormal acth stimulation test results) versus those without hpa axis suppression (217.1 pg/ml vs. 71.2 pg/ml, respectively). secondary safety assessments included serum dheas concentration, local cutaneous adverse events, and teaes. reduction in serum concentration of dheas (which represents an indirect measure of hpa axis suppression) was measured twice during the duration of the study, on treatment day 8 and treatment day 15, both versus the baseline blood sample taken during the screening visit. on day 8, the mean reduction in serum dheas concentration seen in the group treated with imp cream was of lower magnitude than that noted in the group treated with tmv cream, although the difference was not statistically significant (6.8% vs. 19.7%, p = 0.216, table 2). likewise, at day 15, this same trend was noted, but again the difference was not figure 1: percentage of subjects with abnormal acth stimulation test at day 15, stratified by treatment group. figure 2: mean plasma concentration of clobetasol propionate, stratified by treatment group. skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 416 statistically significant (11.0% for the imp group vs. 21.6% for the tmv group, p=0.353, table 2). local cutaneous effects, including development of clinically significant telangiectasia, atrophy, burning or stinging, itch, and pain were evaluated at baseline (day 1 of treatment), day 8, and day 15. no clinically significant telangiectasia or atrophy was noted in any participants in either treatment group throughout the duration of the study. two (8.3%) subjects in the imp group noted clinically significant burning/stinging at baseline (prior to first application of study product) with symptoms resolving in one of the two subjects by day 8 of treatment, whereas the symptoms persisted in the other subject throughout the duration of treatment. in the tmv group, 5 (22.7%) subjects noted clinically significant burning/stinging at baseline (prior to first application of study product), with symptoms persisting to day 8 in 2 (9.1%) of the subjects and throughout the treatment period in 1 (4.5%) subject (figure 3). clinically significant pruritus was reported by 79.2% of subjects in the imp group at baseline, falling to 25% of subjects by the day 15 visit, compared to 81.8% and 31.8% of the tmv group at baseline and day 15, respectively. clinically significant pain was noted in 1 (4.2%) subject in the imp group and 2 (9.1%) subjects in the tmv group at baseline; these symptoms resolved in all 3 subjects by day 8 of treatment. teaes were seen in 6 (25.0%) subjects in the imp treatment group versus 11 (50.0%) in the group treated with tmv cream (table 3). the most common adverse events (other than hpa axis suppression) were local cutaneous symptoms, which were similar in both treatment groups (table 4). analysis of treatment efficacy efficacy results, as measured by the iga scale at baseline and on days 8 and 15, were similar between the two treatment groups, although the study was not powered to demonstrate a significant efficacy difference between the groups (figure 4). at baseline, all subjects had an iga score of 3 or 4 (as required by the criteria for inclusion in the study). at day 15 of treatment, 50% of subjects in each treatment group had an iga score of 2 (mild), and 16.7% of subjects in the imp group and 18.1% in the tmv group had a score of 0 or 1 (null or minimal, respectively). skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 417 figure 3: percentage of subjects with clinically significant application site burning or stinging, stratified by treatment group. figure 4: investigator’s global assessment (iga) of disease severity. skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 418 the results of this phase ii trial, mandated by the fda as part of the approval process for imp cream, suggest that imp cream is a safer alternative to tmv based on reduced hpa axis suppression and reduced systemic exposure to clobetasol propionate. this is an important study as it investigates a key safety outcome: hpa axis suppression, a marker of degree of systemic absorption. although degree of systemic exposure to topical steroids is one of the key concerns with these agents, safety evaluations measuring hpa axis suppression were historically not required for many of the older high-potency topical corticosteroid formulations. for these agents, most information regarding hpa axis suppression was obtained through postmarket reports.9 the present results indicated a 3-fold reduction in hpa axis suppression (with a trend toward statistical significance), and a statistically significant >2.5-fold reduction in circulating plasma clobetasol propionate levels in the group treated with imp, compared to the group treated with tmv. furthermore, in all cases, hpa axis suppression secondary to use of imp cream was reversible. importantly, these findings were observed despite the significant amount of product required in this population with significant bsa involvement. equally important, this was demonstrated in the context of preserved efficacy, as measured by the iga scale. these results, taken together, indicate the potential of imp cream to be used more safely in patients with moderate-to-severe psoriasis who require an adjunct to systemic therapy or in those who are not candidates for systemic therapy. the finding of a lesser degree of hpa axis suppression in patients treated with imp versus tmv is particularly noteworthy as this study was carried out under maximal use conditions in patients with moderate-tosevere disease affecting a significant percentage of the body surface area (2050%). although the proportion of subjects with abnormal acth stimulation test results and the degree of reduction in serum dheas concentration were both numerically lower for subjects treated with imp, the differences were not statistically significant. no statistical justification was made for the sample size of 50 subjects and the study was not powered to detect a statistically significant difference between treatment groups when measuring hpa axis suppression or efficacy. the results of this phase 2 open label clinical study indicate that imp cream (clobetasol propionate 0.025%) is associated with a lower incidence of hpa axis suppression and reduced systemic exposure compared to tmv cream (clobetasol propionate 0.05%) under maximal use conditions in patients with moderate-to-severe plaque psoriasis. this data suggests that compared to traditional dose formulations of clobetasol propionate (0.05%), imp may provide a better safety profile without compromising efficacy. therefore, the use of imp may allow for safer treatment of patients with moderate-tosevere plaque psoriasis who are not candidates for systemic therapy or who would benefit from adjuvant topical therapy in combination with systemic therapy. discussion limitations conclusion skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 419 conflict of interest disclosures: zdd, jff and rc have received honoraria for consulting services from encore dermatology. all authors serve as investigators for encore dermatology. funding: this study was sponsored by encore dermatology. encore dermatology participated in the analysis and interpretation of data. acknowledgements: the authors would like to acknowledge javier alonso-llamazares md phd, ellen h. frankel md, herschel stoller md, francisco flores md, gary lee heller do, john michael humeniuk md, hector wiltz md, allan m. soo md, tooraj raoof md, mark a. knautz md, seth b. forman md, and james f. pehoushek md mph, all of whom served as co-investigators in this phase ii trial. corresponding author: zoe d. draelos, md dermatology consulting services, pllc high point, nc zdraelos@northstate.net references: 1. samarasekera ej, sawyer l, wonderling d, tucker r, smith ch. topical therapies for the treatment of plaque psoriasis: systematic review and network meta-analyses. the british journal of dermatology. 2013;168(5):954-967. 2. decani s, federighi v, baruzzi e, sardella a, lodi g. iatrogenic cushing's syndrome and topical steroid therapy: case series and review of the literature. the journal of dermatological treatment. 2014;25(6):495-500. 3. guin jd. complications of topical hydrocortisone. journal of the american academy of dermatology. 1981;4(4):417422. 4. gilbertson eo, spellman mc, piacquadio dj, mulford mi. super potent topical corticosteroid use associated with adrenal suppression: clinical considerations. journal of the american academy of dermatology. 1998;38(2 pt 2):318-321. 5. bartley pc. topical steroids and hypothalamo-pituitary-adrenal suppression: a review. the australasian journal of dermatology. 1978;19(3):109113. 6. mcdonough rj, alba p, dileepan k, cernich jt. employing a results-based algorithm to reduce laboratory utilization in acth stimulation testing. journal of pediatric endocrinology & metabolism : jpem. 2018;31(4):429-433. 7. langley rg, feldman sr, nyirady j, van de kerkhof p, papavassilis c. the 5-point investigator's global assessment (iga) scale: a modified tool for evaluating plaque psoriasis severity in clinical trials. the journal of dermatological treatment. 2015;26(1):23-31. 8. nakamura m, abrouk m, zhu h, farahnik b, koo j, bhutani t. update on the systemic risks of superpotent topical steroids. journal of drugs in dermatology : jdd. 2017;16(7):643-648. 9. walsh p, aeling jl, huff l, weston wl. hypothalamus-pituitary-adrenal axis suppression by superpotent topical steroids. journal of the american academy of dermatology. 1993;29(3):501-503. mailto:zdraelos@northstate.net skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 420 appendix 1: participant flow through the study. a prospective, multicenter, randomized, double-blind, vehicle-controlled phase 2 study to evaluate the safety and efficacy of a combination of 3% minocycline and 0.3% adapalene topical foam formulation for the treatment of moderate-to-severe acne james q. del rosso, do1; linda stein gold, md2; zoe draelos, md3; tooraj joseph raoof, md4; deirdre hooper, md5; iain stuart, phd6 1jdr dermatology research/thomas dermatology, las vegas, nv; 2henry ford health system, detroit, mi; 3dermatology consulting services, high point, nc; 4t. joseph raoof, md, inc./encino research center, encino, ca; 5audubon dermatology, new orleans, la; 6vyne therapeutics inc., bridgewater, nj introduction • acne vulgaris is a common disease of both males and females, usually manifesting initially during adolescence and affecting most of the population at some point during their lifetime1-3 • acne is frequently treated with antibiotics, retinoids, or both1,4 – minocycline is a second-generation tetracycline with bacteriostatic and anti inflammatory properties2,5 – adapalene is a third-generation retinoid that has anti-inflammatory and comedolytic properties, and normalizes keratinization1 • a fixed combination of minocycline 3% and adapalene 0.3%, fcd105, has been developed as a novel topical foam for the treatment of moderate-to-severe acne – both of these molecules are used individually or in combination with other agents (eg, benzoyl peroxide) in fda-approved treatments for acne although a retinoid/tetracycline topical formulation had not been evaluated in clinical studies prior to this study and may offer an improved treatment option for patients with moderate-to-severe acne • the objectives of this study are: – to evaluate the safety, tolerability, and efficacy of the combination product fcd105 in the treatment of moderate-to-severe acne vulgaris with up to 12 weeks of daily treatment, in comparison with vehicle – to compare the efficacy and safety of fcd105 against the individual, active-drug components: minocycline 3% and adapalene 0.3% topical foam products methods • study fx2016-40 was a randomized, multicenter, double-blind, vehicle-controlled, phase 2 study – the purpose was to evaluate the safety, tolerability, and efficacy over a 12-week treatment period of fcd105 as compared with vehicle foam and the individual active components of fcd105 in the treatment of subjects with moderate-to-severe acne vulgaris in a 2x2 factorial design (figure 1) • study drug administration – subjects were randomized 5:3:4:4 to one of the following 4 color-matched foam treatments: fcd105 (minocycline 3% + adapalene 0.3%), vehicle, minocycline 3%, or adapalene 0.3% � overall, there was high rate of study completion; 417 (93.3%) of the 447 subjects who were included in the itt population completed the study, with comparable completion rates between treatment groups (figure 1) – the assigned study treatment was applied once daily for 12 weeks • co-primary efficacy endpoints – absolute change in inflammatory and noninflammatory lesion counts from baseline to week 12 for fcd105 vs. vehicle – percent of subjects achieving iga treatment success at week 12, where success was defined as a score of 0 (clear) or 1 (minimal) and a ≥2-grade improvement (decrease) from baseline for fcd105 vs. vehicle • secondary efficacy endpoints – percentage change of inflammatory and noninflammatory lesion count for fcd105 vs vehicle at weeks 4, 8, and 12 – absolute change of inflammatory and noninflammatory lesion count for fcd105 vs minocycline 3% and fcd105 vs. adapalene 0.3% from baseline to week 12 – percent of patients achieving iga treatment success at week 12 for fcd105 vs minocycline 3% and fcd105 vs. adapalene 0.3% • safety evaluations – treatment-emergent adverse events, local skin tolerability assessments, vital signs, and physical examinations • a subject satisfaction questionnaire was completed at baseline and week 12 figure 1. study design key inclusion criteria • ≥12 years of age • 20–50 inflammatory lesions • 25–100 noninflammatory lesions • iga score of 3/4 • ≤2 active face nodules baseline fcd105 foam: itt, n=142; safety, n=142; completed, n=130 (91.5%) vehicle foam; itt, n=83; safety, n=82; completed, n=80 (96.4%) minocycline 3% foam: itt, n=110; safety, n=110; completed, n=106 (96.4%) adapalene 0.3% foam: itt, n=112; safety, n=112; completed, n=101 (90.2%) week 4 week 8 week 12 (end of treatment) week 16 (safety fu) subjects were randomized 5:3:4:4 to treatment with combination, vehicle, or an individual active component, respectively, from 35 u s sites iga=investigator’s global assessment, based upon a 5-point scale in which 0=clear, 1=minimal, 2=mild, 3=moderate, and 4=severe; fu, follow-up; itt=intent-to-treat. results baseline demographics and disease characteristics (itt population) • baseline demographics and disease characteristics were similar across treatment groups (table 1) • the majority of subjects were white (70.7%) and female (61.1%); mean age was 21.3 years • the average inflammatory and noninflammatory lesion counts across groups at baseline were 30.6 and 48.1, respectively; the majority of subjects (90.8%) had moderate (iga=3) disease severity at baseline table 1. baseline demographics and disease characteristics (itt population) variable fcd105 (n=142) vehicle (n=83) minocycline 3% (n=110) adapalene 0.3% (n=112) overall (n=447) age (years), mean (sd) 21.0 (7.05) 21.4 (7.25) 20.8 (8.28) 22.0 (7.98) 21.3 (7.63) age groups, n (%) <18 years 64 (45.1) 32 (38.6) 55 (50.0) 41 (36.6) 192 (43.0) 18–40 years 76 (53.5) 50 (60.2) 52 (47.3) 70 (62.5) 248 (55.5) 41–64 years 2 (1.4) 1 (1.2) 3 (2.7) 1 (0.9) 7 (1.6) sex, n (%) male 62 (43.7) 33 (39.8) 43 (39.1) 36 (32.1) 174 (38.9) female 80 (56.3) 50 (60.2) 67 (60.9) 76 (67.9) 273 (61.1) ethnicity, n (%) hispanic or latino 63 (44.4) 33 (39.8) 47 (42.7) 43 (38.4) 186 (41.6) not hispanic or latino 79 (55.6) 50 (60.2) 63 (57.3) 69 (61.6) 261 (58.4) race, n (%) america indian or alaska native 1 (0.7) 0 (0.0) 0 (0.0) 0 (0.0) 1 (0.2) asian 7 (4.9) 6 (7.2) 5 (4.5) 2 (1.8) 20 (4.5) black or african american 29 (20.4) 15 (18.1) 23 (20.9) 27 (24.1) 94 (21.0) native hawaiian or other pacific islander 0 (0.0) 1 (1.2) 0 (0.0) 0 (0.0) 1 (0.2) white 103 (72.5) 56 (67.5) 81 (73.6) 76 (67.9) 316 (70.7) multiple 0 (0.0) 4 (4.8) 0 (0.0) 4 (3.6) 8 (1.8) not reported 2 (1.4) 1 (1.2) 1 (0.9) 3 (2.7) 7 (1.6) inflammatory lesion count, mean (sd) 30.2 (7.6) 30.0 (8.1) 31.0 (8.7) 31.1 (8.6) 30.6 (8.2) noninflammatory lesion count, mean (sd) 47.2 (16.7) 49.8 (16.5) 48.4 (19.1) 47.8 (16.9) 48.1 (17.3) iga score moderate (iga=3) 134 (94.4) 76 (91.6) 96 (87.3) 100 (89.3) 406 (90.8) severe (iga=4) 8 (5.6) 7 (8.4) 14 (12.7) 12 (10.7) 41 (9.2) efficacy data • fcd105 showed a statistically significant improvement compared with vehicle for the co-primary endpoints of iga treatment success (figure 2a) and absolute change in inflammatory lesions (figure 2b) at week 12 – by week 12, a significantly greater percent of subjects in the fcd105 group achieved iga treatment success compared with the vehicle group – daily application of fcd105 resulted in a significantly greater reduction in inflammatory lesions at week 12 compared with the vehicle group • a numerical advantage of fcd105 vs. vehicle was observed in the absolute change in noninflammatory lesions at week 12 (figure 2c) figure 2. co-primary efficacy endpoints at week 12 (itt population with mi) iga treatment success 35.9 15.7 0 5 10 15 20 25 30 35 40 45 50 fcd105 (n=142) vehicle (n=83) p er ce nt o f s ub je ct s ac hi ev in g ig a tr ea tm en t s uc ce ss a t w ee k 12 a p=0.0003b a fcd105 (n=142) vehicle (n=83) a bs ol ut e ch an ge fr om b as el in e in in fla m m at or y le si on s at w ee k 12 c b absolute reduction in inflammatory lesions –24.9 -–30 –25 –20 –15 –10 –5 0 fcd105 (n=142) vehicle (n=83) a bs ol ut e ch an ge fr om b as el in e in no nin fla m m at or y le si on s at w ee k 12 c c absolute reduction in noninflammatory lesions p=0.321d 30.2e 30.0e 47.2e 49.8e –19.4 –15.6 –22.9p=0.002d –30 –25 –20 –15 –10 –5 0 mi=multiple imputation. aiga treatment success is defined as an iga score of 0 or 1, and at least a 2-grade improvement (decrease) from baseline. bcochran-mantel-haenszel test stratified by analysis center. p-value is for the null hypothesis that the risk ratio equals 1. cplotted data show the least squares means, which are defined as a model-based linear combination of the estimated effects. dp-values are obtained from ancova model with treatment as a main effect, baseline inflammatory lesion count as a covariate, and analysis center as a blocking factor. emean baseline lesion counts. • a significantly greater percent of subjects in the fcd105 group achieved iga treatment success than those in the vehicle group as early as week 8 (figure 3a) • the time course of the percent change in inflammatory lesions from baseline demonstrated a numerical advantage of fcd105 over vehicle as early as week 4; this difference became significant at week 12 (figure 3b) • for the percent change in noninflammatory lesions, a numerical advantage of fcd105 over vehicle was observed by week 8 and maintained at week 12 (figure 3c) figure 3. efficacy of fcd105 throughout the study duration (itt population with mi) p er ce nt c ha ng e in n il s fr om b as el in ec –75 –50 –25 0 0 4 8 12 fcd105 (n=142) vehicle (n=83) fcd105 (n=142) vehicle (n=83) week –15.3 –34.3 –51.0 –17.3 –29.9 –45.9 p=0.6641d p=0.3573d p=0.2452d iga treatment successa b percent change in ils c percent change in nils 0.0 3.5 14.8 35.9 0.0 2.4 8.4 15.7 0 0 4 week 8 12 5 10 15 20 25 30 35 40 45 50 s ub je ct s (% ) ac hi ev in g ig a tr ea tm en t s uc ce ss a p=0.0491b p=0.0003b fcd105 (n=142) vehicle (n=83) p er ce nt c ha ng e in il s fr om b as el in ec –75 –50 –25 0 0 4 8 12 p=0.1486d p=0.4161d p=0.0013d fcd105 (n=142) vehicle (n=83) week –32.9 –50.0 –64.1 –27.3 –46.7 –50.9 ils-inflammatory lesions; nils=non-inflammatory lesions. aiga treatment success is defined as an iga score of 0 or 1, and at least a 2-grade improvement (decrease) from baseline. bcochran-mantel-haenszel test stratified by analysis center. p-value is for the null hypothesis that the risk ratio equals 1. cplotted data show the least squares means, which are defined as a model-based linear combination of the estimated effects. dp-values are obtained from ancova model with treatment as a main effect, baseline inflammatory lesion count as a covariate, and analysis center as a blocking factor. • fcd105 achieved all secondary efficacy endpoints by demonstrating a numerical advantage over both individual components in the percent of subjects achieving iga treatment success (figure 4a) and the absolute reduction in noninflammatory lesions (figure 4c) at week 12, as well as demonstrating a lack of numerical inferiority to either component in the absolute reduction in inflammatory lesions at week 12 (figure 4b) – fcd105 showed statistically significant improvements compared with adapalene 0.3% in all three endpoints at week 12 – there was a significantly greater reduction in noninflammatory lesions at week 12 in the fcd105 group compared with the minocycline 3% group figure 4. secondary efficacy endpoints at week 12 (itt population with mi) 25.4 19.1 20.7 p=0.0033d p=0.0292d –19.7 –18.7 –15.8 30.2e 31.0e 31.1e p=0.4053d p=0.0012d 47.2e 48.4e 47.8e 0 5 10 15 20 25 30 35 40 45 50 p er ce nt o f s ub je ct s ac hi ev in g ig a tr ea tm en t s uc ce ss a t w ee k 12 a a a bs ol ut e ch an ge fr om b as el in e in in fla m m at or y le si on s at w ee k 12 c b –30 –25 –20 –15 –10 –5 0 a bs ol ut e ch an ge fr om b as el in e in no nin fla m m at or y le si on s at w ee k 12 c c fcd105 (n=142) minocycline 3% (n=110) adapalene 0.3% (n=112) 35.9 30.0 21.4 p=0.2569b p=0.0114b –30 –25 –20 –15 –10 -5 0 iga treatment success absolute reduction in inflammatory lesions absolute reduction in noninflammatory lesions mi=multiple imputation. aiga treatment success is defined as an iga score of 0 or 1, and at least a 2-grade improvement (decrease) from baseline. bcochran-mantel-haenszel test stratified by analysis center. p-value is for the null hypothesis that the risk ratio equals 1. cplotted data show the least squares means, which are defined as a model-based linear combination of the estimated effects. dp-values are obtained from ancova model with treatment as a main effect, baseline inflammatory lesion count as a covariate, and analysis center as a blocking factor. emean baseline lesion counts. safety summary • a summary of all aes in the safety population is shown in table 2 • there were no serious aes reported during the course of the study • overall, most subjects reported aes that were mild (10.3%) or moderate (4.0%) in severity – the incidence rate of severe aes was similar across treatment groups – 2 subjects (0.4%) reported severe aes • a total of 4 subjects (0.9%) reported aes that led to discontinuation of study drug table 2. overall summary of adverse events (safety population) fcd105 (n=142) vehicle (n=82) minocycline 3% (n=110) adapalene 0.3% (n=112) overall (n=446) subjects with any ae, n (%) 21 (14.8) 10 (12.2) 15 (13.6) 20 (17.9) 66 (14.8) maximum severity, n (%) mild 12 (8.5) 7 (8.5) 13 (11.8) 14 (12.5) 46 (10.3) moderate 9 (6.3) 3 (3.7) 2 (1.8) 4 (3.6) 18 (4.0) severe 0 (0.0) 0 (0.0) 0 (0.0) 2 (1.8)a 2 (0.4) subjects with any treatment-related ae, n (%) 5 (3.5) b 0 (0.0) 2 (1.8)c 10 (8.9)d 17 (3.8) subjects with any sae, n (%) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) subjects with any ae leading to discontinuation, n (%) 1 (0.7)e 0 (0.0) 0 (0.0) 3 (2.7)f 4 (0.9) subjects with any ae leading to death, n (%) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) ae=adverse event; teae=treatment-emergent adverse event; sae=serious adverse event a2 cases of acne. bdry skin, rash, dermatitis contact, pain of skin, burning sensation, and hyperesthesia. cdry skin and nail discoloration. d4 cases of dry skin, 2 cases each of rash, acne, and eye irritation, and 1 case each of skin discoloration, skin irritation, and erythema of eyelid. eacne. f2 cases of acne and 1 case of rash. • the incidence rate of the most frequently reported teaes (≥2% in any group) was similar between treatment groups (table 3) • three subjects withdrew from the study due to a treatment-related teae, all in the adapalene 0.3% group: acne, n=2 (1.8%); rash, n=1 (0.9%). there were no saes reported during the conduct of the study table 3. summary of teaes occurring in >2% of subjects in any treatment group (safety population) system organ class/ preferred term, n (%)a fcd105 (n=142) vehicle (n=82) minocycline 3% (n=110) adapalene 0.3% (n=112) overall (n=446) infections and infestations upper respiratory tract infection 2 (1.4) 4 (4.9) 3 (2.7) 1 (0.9) 10 (2.2) nasopharyngitis 2 (1.4) 0 (0.0) 3 (2.7) 0 (0.0) 5 (1.1) viral upper respiratory tract infection 0 (0.0) 2 (2.4) 0 (0.0) 1 (0.9) 3 (0.7) skin and subcutaneous tissue disorders dry skin 2 (1.4) 0 (0.0) 1 (0.9) 4 (3.6) 7 (1.6) nervous system disorders headache 1 (0.7) 3 (3.7) 2 (1.8) 2 (1.8) 8 (1.8) asummary of teaes occurring in >2% of subjects in any treatment group, listed in descending order based on the overall total within each system organ class. • local facial tolerability assessments at week 12 demonstrated that fcd105 was well tolerated (figure 5) • the majority of subjects (≥89.9%) across all treatment groups recorded local tolerability assessments as “none” or “mild” at week 12; no notable differences were observed between treatment groups • at least 93% of subjects treated with fcd105 rated local facial tolerability as “none” or “mild” for all 6 measures of local facial tolerability figure 5. local facial tolerability assessments at week 12 (safety population, observed cases) 0 bl wk 4 wk 8 wk 12 bl wk 4 wk 8 wk 12 bl wk 4 wk 8 wk 12 bl wk 4 wk 8 wk 12 bl wk 4 wk 8 wk 12 bl wk 4 wk 8 wk 12 0.25 0.5 0.75 1 m ea n s ev er ity s co re ( ra ng e of 0 =n on e to 3 =s ev er e) a itching hyperpigmentationerythemascalingdrynessburning and stinging fcd105 vehicle minocycline 3% adapalene 0.3% bl=baseline; wk4=week 4; wk8=week8; wk12=week 12. alocal signs and symptoms were assessed on a 4-point scale including 0=none, 1=mild, 2=moderate, and 3=severe. summary limitations • a limitation of the study relates to the generalizability of the data to a larger population or to patients less than 12 years of age • future studies are needed to confirm these findings and evaluate the safety profile of fcd105 over longer treatment durations conclusions • statistically significant improvement in disease burden was observed for fcd105 foam vs vehicle foam for the absolute change in inflammatory lesion count and iga treatment success at week 12 • numerical superiority was demonstrated for fcd105 over vehicle foam for the absolute change in noninflammatory lesions at week 12 • numerical advantage of fcd105 foam over both minocycline 3% foam and adapalene 0.3% foam was observed at week 12, with the majority of comparisons being statistically significant • teaes were few in type and frequency. most were mild in severity, no serious teaes were reported, and subject discontinuations due to teaes were low • fcd105 demonstrated a favorable tolerability profile, with most (≥93%) local signs and symptoms in this group being reported as “none” or “mild” at week 12 • these data are supportive to continue the development of fcd105 into phase 3 clinical evaluation for the treatment of moderate-to-severe acne vulgaris funding this study was funded by foamix pharmaceuticals ltd, a wholly owned subsidiary of vyne therapeutics inc. disclosures/acknowledgments disclosures dr. del rosso is a consultant for aclaris, almirall, athenex, cutanea, dermira, ferndale, galderma, genentech, leo pharma, menlo, novan, ortho, pfizer, promius, sanofi/regeneron, skinfix, and sunpharma; he has received research support from aclaris, almirall, athenex, botanix, celgene, cutanea, dermira, galderma, genentech, leo pharma, menlo, novan, ortho, promius, regeneron, sunpharma, and thync; he receives honoraria from aclaris, celgene, galderma, genentech, leo pharma, novartis, ortho, pfizer, promius, sanofi/regeneron, and sunpharma; and he participates in speakers bureaus for honoraria from aclaris, celgene, galderma, genentech, leo pharma, novartis, ortho, pfizer, promius, sanofi/regeneron, and sunpharm. dr. stein gold is an advisor and investigator for foamix pharmaceuticals inc, galderma, leo pharma, novartis, and valeant and is an investigator for janssen, abbvie, and solgel. dr. draelos is a principal investigator and advisor for foamix pharmaceuticals inc. dr. raoof is an investigator for foamix pharmaceuticals inc. dr. hooper has served as an investigator for foamix pharmaceuticals; she reports honoraria from allergan, almirall aesthetics, aqua galderma usa, cutera, inc., ferndale, la roche posay, pixacore, rbc consultants (clarisonic), revance, and viviscal; she reports other financial benefits from actavis, dermira, gsk, mylan, and sol gel. dr. stuart is an employee and stockholder at vyne therapeutics inc. acknowledgments editorial support was provided by scient healthcare communications. references 1. thiboutot dm, dréno b, abanmi a, et al. practical management of acne for clinicians: an international consensus from the global alliance to improve outcomes n acne. j am acad dermatol. 2018;78(2s1):s1-s23.e1. 2. garner se, eady a, bennett c, et al. minocycline for acne vulgaris: efficacy and safety. cochrane database syst rev. 2012;cd002086. 3. yentzer ba, hick j, reese el, et al. acne vulgaris in the united states: a descriptive epidemiology. cutis. 2010;86:94-99. 4. zaenglein al, pathy al, schlosser bj, et al. guidelines of care for the management of acne vulgaris. j am acad dermatol. 2016;74:945-973. 5. garrido-mesa n, zarzuelo a, gálvez j. minocycline: far beyond an antibiotic. br j pharmacol. 2013;169:337-352. skin july 2018 volume 2 issue 4 copyright 2018 the national society for cutaneous medicine 243 brief article cutaneous rosai-dorfman disease: a case report nahla shihab md a , whitney talbott md b , parth desai bs c , nathalie o kahn d , erisa alia md e , jeffrey m. weinberg md f a resident physician, department of dermatology and venereology, universitas indonesia/cipto mangunkusumo national hospital, jakarta, indonesia b resident physician, department of dermatology, mount sinai medical center, new york, ny c medical center, mercer university school of medicine, macon, ga d undergraduate student, barnard college, columbia university, new york, ny e research fellow, department of dermatology, mount sinai medical center, new york, ny f associate clinical professor of dermatology, mount sinai st. luke’s, mount sinai beth israel, new york, ny rosai-dorfman disease (rdd) or sinus histiocytosis with massive lymphadenopathy (shml) is a benign, self-limited proliferation of histiocytosis, first described by rosai and dorfman in 1969. 1-3 rdd may involve the skin secondary to multi-organ involvement, or it may solely involve the skin without any other organ involvement. in the latter scenario, the disease is classified as cutaneous rosai-dorfman disease (crdd). 1-5 crdd is believed to be a distinct entity because of its unique epidemiologic pattern and the absence of systemic manifestations. 4-5 it is also considered a rare entity, with only a few cases reported in the literature. 5 we report the case of a biopsy and immunohistochemistry proven crdd, in a young african american woman. a 23-year-old african american woman presented with a growth on her right thigh for roughly 2 years, which had been progressively enlarging and darkening. new lesions developed on her chest, back, and buttocks, though some resolved abstract cutaneous rosai-dorfman disease (crdd) is an uncommon benign histiocytosis of unknown etiology. crdd is oftentimes misdiagnosed because it has variable clinical manifestations, particularly in the absence of lymphadenopathy. we report a case of a 23year-old african american woman presenting with clustered nodular plaques on her right thigh, buttocks, back, and chest for the past two years. history, clinical, histopathological, and immunochemistry findings corresponded with crdd, and as such, she was treated with halobetasol propionate 0.05% cream twice daily. introduction case report skin july 2018 volume 2 issue 4 copyright 2018 the national society for cutaneous medicine 244 spontaneously over time. her personal and family history were unremarkable. she had no fever, weight loss, or gastrointestinal complaints. upon physical examination, there were clusters of pink and brown, hyperpigmented papules and nodules on her right thigh, chest, back and buttocks. in addition, she had several satellite nodules on her left upper arm and abdomen. all of her skin lesions were slightly tender to palpation (figure 1). there was no cervical, axillary, or inguinal lymphadenopathy present, nor was there organomegaly present. her laboratory results were within normal limits, and her chest radiogram was normal. a skin biopsy from a lesion on her right thigh revealed a dermal histiocytic and lymphoplasmytic infiltrate with fibrosis and telangiectasia (figure 2). stains were negative for fungal (gms) and mycobacterial (fite) microorganisms. s100 immunohistochemistry highlighted histiocytic proliferation with features of emperipolesis suggestive of cutaneous rosai-dorfman disease (figure 3). after diagnostic confirmation, the patient was treated with halobetasol propionate 0.05% cream twice daily, only to symptomatic lesions. figure 1. clusters of pink and brown, hyperpigmented papules and nodules in patients with cutaneous rosaidorfman disease figure 2. a nodular proliferation of histiocytic cell infiltrates involves dermis with an interstitial and perivascular inflammation. skin july 2018 volume 2 issue 4 copyright 2018 the national society for cutaneous medicine 245 figure 3. emperipolesis rosai-dorfman disease (rdd) is a benign disorder of proliferative histiocytosis, that most often presents with lymphadenopathy. 1-5 rdd typically affects cervical lymph nodes and is accompanied by fever, leukocytosis, elevated erythrocyte sedimentation rate (esr), and polyclonal hypergammaglobulinemia. 1-2, 5 extranodal involvement may occur, with the skin being the most common site. 1-2 when rdd is limited to the skin, it is considered a different and rarer entity known as cutaneous rosaidorfman disease (crdd). 1, 5 crdd may manifest as nodules, papules, pustules, plaques, and patches without specific predilection of the body site involved. 1, 6 our patient presented with clustered satellite nodules, somewhat mimicking keloid (figure 1). she did not have any organ involvement or lymphadenopathy. the differential diagnosis for crdd in this patient included: fibrous histiocytoma, xanthoma, juvenile xanthogranuloma, reticulohistiocytoma, mycobacterial or deep fungal infections, and lymphoproliferative disease. 1 the age distribution of crdd ranges from 15 to 68 years, with female predominance of 2:1 1 . the exact etiopathogenesis of rdd/crdd is not known, but it is believed to originate from an overactive immune response discussion skin july 2018 volume 2 issue 4 copyright 2018 the national society for cutaneous medicine 246 leading to histiocyte expansion and activity. 7 pathogens such as human herpes virus (hhv), epsein-barr virus (ebv), varicellazoster virus (vzv), and human immunodeficiency virus (hiv) have been reported as possible stimuli for the disease. 8 the most sensitive and specific diagnostic tool for crdd is histologic examination, particularly in the absence of lymphadenopathy and other systemic symptoms. histological appearance of crdd is indistinguishable from rdd, with both characterized by proliferation of polygonal histiocytes (rosai-dorfman cell) showing emperipolesis and a mixed inflammatory infiltrate. 1-2 the classic rosaidorfman cell is recognized by abundant amorphous cytoplasm, indistinct borders, and a large vesicular nucleus with prominent nucleoli. 2 these cells uniquely express the dendritic/langerhans cell marker s-100 and also monocyte/macrophage markers such as lysozyme, mac-387 and cd68. 9 emperipolesis can be evident by observing trapped and intact lymphocytes inside of histiocytes which are not digested 10 , a characteristic finding that was also seen in our patient’s biopsy (figure 3). crdd has a good prognosis and usually spontaneously resolves, although persistent disease can also occur in some. 8 a portion of the lesions in our patient resolved spontaneously, however others have been persistent for over a year. various therapeutic modalities have been reported for crdd including corticosteroids 11 , isotretinoin 12 , thalidomide 13 , cryotherapy 14 , radiotherapy 15 , and surgery 16 . our patient was treated with the topical steroid halobetasol to symptomatic lesions. we suggested to watch and wait until the lesions resolved spontaneously, since most cutaneous lesions do not require treatment unless cosmetically unacceptable to the patients. purely cutaneous rosai-dorfman disease is a very rare and difficult diagnosis to be made, because it has no characteristic features of the skin disease. nevertheless, a dermatologist should be able to diagnose this disease with the use of histopathological examination and immunochemistry. conflict of interest disclosures: none funding: none corresponding author: nahla shihab, md universitas indonesia/cipto mangunkusumo national hospital, jakarta, indonesia +6221-31935383 (office) +6221-3905072 (fax) nahla.shihab@gmail.com references: 1. brenn t, calonje e, granter sr, leonard n, grayson w, fletcher cd, et al. cutaneous rosai-dorfman disease is a distinct clinical entity. am j dermatopathol. 2002;24(5):38591. 2. wang k-h, chen w-y, liu h-n, huang c-c, lee w-r, hu c-h. cutaneous rosai–dorfman disease: clinicopathological profiles, spectrum and evolution of 21 lesions in six patients. br j dermatol. 2006;154(2):277-86. 3. rubenstein ma, farnsworth nn, pielop ja, orengo if, curry jl, drucker cr, et al. cutaneous rosai-dorfman disease. dermatol online j. 2006;12(1):8. conclusion skin july 2018 volume 2 issue 4 copyright 2018 the national society for cutaneous medicine 247 4. farooq u, chacon ah, vincek v, elgart gw. purely cutaneous rosai-dorfman disease with immunohistochemistry. indian j dermatol. 2013;58(6):447-50. 5. hinojosa t, ramos e, lewis dj, angel ld, vangipuram r, peranteau aj, et al. cutaneous rosai-dorfman disease: a separate clinical entity. j dermatol & dermatol surg. 2017;21(2):107-9. 6. jia j, tian q, zhang h, zheng y. an unusual case of multiple cutaneous rosai-dorfman disease involving two separate parts of the body. int j dermatol. 2017;56(5):576-8. 7. kinio ae, sawchuk ma, pratt m. atypical primary cutaneous rosai-dorfman disease: a case report. j cutan med surg. 2017;21(5):460-3. 8. khoo jj, rahmat bo. cutaneous rosaidorfman disease. malaysian j pathol. 2007;29(1):49-52. 9. middel p, hemmerlein b, fayyazi a, kaboth u, radzun hj. sinus histiocytosis with massive lymphadenopathy: evidence for its relationship to macrophages and for a cytokine-related disorder. histopathology. 1999;35(6):525-33. 10. landim fm, rios hdo, costa co, feitosa rgf, filho fdr, costa aaa. cutaneous rosaidorfman disease. an bras dermatol. 2009;84(3):1-5. 11. salim a, williamson m, barker f, hughes j. steroid responsive cutaneous rosai–dorfman disease associated with uveitis and hypothyroidism. clin exp dermatol. 2002;27(4):277-9. 12. kong y, kong j, shi d, lu h, zhu x, wang j. cutaneous rosai-dorfman disease a clinical and histopathologic study of 25 cases in china. am j surg pathol. 2007;31:341-50. 13. lu c-i, kuo t-t, wong w-r, hong h-s. clinical and histopathologic spectrum of cutaneous rosai-dorfman disease in taiwan. j am acad dermatol. 2004;51(6):931-9. 14. scheel mm, rady pl, tyring sk, pandya ag. sinus histiocytosis with massive lymphadenopathy: presentation as giant granuloma annulare and detection of human herpesvirus 6. j am acad dermatol. 1997;37(4):643-6. 15. annesi g, giannetti a. purely cutaneous rosai-dorfman disease. br j dermatol. 1996;134(4):749-53. 16. lai fm-m, lam wy, chin cw, ng wl. cutaneous rosai-dorfman disease presenting as a suspicious breast mass. j cutan pathol. 1994;21(4):377-82. skin may 2018 volume 2 issue 3 copyright 2018 the national society for cutaneous medicine 172 opinion piece evaluating the utility of self and clinical skin examinations to screen for skin cancer: the importance of considering publications of all levels of evidence ryan m. svoboda md ms a , clay j. cockerell md mba b , roger i. ceilley md c,d , darrell s. rigel md ms e a national society for cutaneous medicine, new york, ny b departments of dermatology and pathology, university of texas southwestern dallas, tx c dermatology p.c., west des moines, ia d department of dermatology, university of iowa carver college of medicine, iowa city, ia e ronald o. perelman department of dermatology, nyu school of medicine, new york, ny in the recent updates to their evidencebased recommendation statements on the utility of clinical skin examination (cse) 1 and self-skin examination (sse) 2 for skin cancer primary prevention, the united states preventative services task force (uspstf) concluded that there was insufficient evidence to recommend for or against both cse and sse. these statements have evoked considerable confusion, frustration, and controversy in the dermatology community. understanding the controversy at the heart of this situation requires a close look at the basic tenets of evidence-based practice, and how they have evolved. the term “evidencebased medicine,” as it was originally described, referred to the critical appraisal of the literature by the individual clinician to aid in decision making and patient counseling. 3 this has since grown into a more expansive concept that emphasizes the development of overarching guidelines and recommendation statements by working groups assigned to appraise the primary literature. while guidelines certainly have great potential if properly comprised, this process has in many cases decentralized the role of the individual practitioner in evaluating the literature directly. rather than follow any recommendation statement blindly, it is imperative that the astute clinician reviews the underlying methodology prior to determining how and to what degree the guidelines will be incorporated into daily practice. in the case of the recent uspstf recommendations, such an exercise will reveal several methodological flaws, but the critical drawback (and the focus of this editorial) is the task force’s overreliance on individual studies’ “level of evidence.” this is an increasingly pervasive problem in the modern medical landscape and underscores the scientific community’s misinterpretation of the original intent of the evidence-based medicine movement. to grade the strength of their recommendations, the uspstf uses a skin may 2018 volume 2 issue 3 copyright 2018 the national society for cutaneous medicine 173 scale based on the level of evidence inherent to the designs of the individual studies that they review. the critical error in their methodology, however, is that they place an disproportionately high value on results from meta-analyses and randomized controlled trials (rcts) while giving much less consideration to prospective cohort studies and often completely discounting any existing evidence from retrospective cohort studies, case-control studies, and cross-sectional studies. for example, in their recommendation on sse, they state that there is a lack of evidence linking this practice to lower incidence of skin cancer or other outcomes such as decreased mortality. however, multiple observational studies demonstrating material benefits to sse exist, including a widely-cited casecontrol study by berwick, et al. which revealed the potential of self-examination to reduce melanoma-related mortality by as much as 63%. 4 failing to include all study designs is a major oversight. the original tenets of evidencebased medicine make it clear that the practice should not be limited to metaanalyses and rcts alone. 3 although these studies are important because they can eliminate confounding and demonstrate causality, other study designs have merit as well and should not be completely discounted. while there is value in recognizing the hierarchy of evidence, sole reliance on study design is a flawed tactic. rather, close assessment of all aspects of each individual study is important. after all, the results of a poorly constructed, heavily biased rct are undoubtedly less useful than those of a well-designed retrospective cohort study, but the uspstf’s methods would place significant weight on the former while potentially discounting the latter altogether. furthermore, there are some cases in which an rct cannot feasibly be performed due to ethical concerns or other prohibitively challenging circumstances. in such instances, it would be foolhardy to ignore evidence from observational studies. this point is expertly illustrated by a satirical “study” by smith and pell, who after attempting a meta-analysis of rcts examining the benefits of parachute use during free fall, humorously concluded that there was insufficient evidence to recommend parachute use when jumping from an airplane due to the lack of rcts examining this intervention. 5 similarly, there surely are no trials randomizing cardiac arrest patients to cardiopulmonary resuscitation (cpr) versus no intervention. does that mean that we should publish guidelines concluding insufficient evidence to recommend for or against the use of cpr in patients who suffer cardiac arrest? another example, pertinent to the dermatology community, is the surgical treatment of skin cancer. one would be hard-pressed to find a study randomizing patients with biopsy-proven melanoma to observation versus surgical excision, yet clearly the former treatment course would be considered unfathomable in all but the most extreme of circumstances. these examples may seem radical, but they illustrate the point. when one considers the exorbitant costs (due to the large number of patients that would need to be followed for many years to demonstrate a significant difference), ethical problems (of withholding screening) that would lead to low enrollment, and bias issues (how could we ensure that patients randomized to no intervention were not looking at their own skin?), it becomes clear just how prohibitive conducting a highquality rct of cse and/or sse in this realm would be. skin may 2018 volume 2 issue 3 copyright 2018 the national society for cutaneous medicine 174 although we applaud the uspstf’s efforts to generate evidence-based guidelines on skin examination, the current system has material deficiencies that may impact any conclusions which they draw. until they revisit their methods and deliver recommendations that more appropriately consider all existing evidence, providers of dermatologic care must continue to advocate the importance of cse and sse in the prevention of skin cancer. we encourage groups like the uspstf to better integrate observational and anecdotal evidence so that skin exams (like parachutes and cpr) will no longer continue to be under threat of denouncement as a viable life-saving option. conflict of interest disclosures: none funding: none corresponding author: ryan m. svoboda, md, ms 35 e. 35 th st., ste. 208 new york, ny 11101 646-341-6468 212-689-5748 rmsvoboda@gmail.com references: 1. united states preventative services task force. screening for skin cancer: us preventive services task force recommendation statement. jama. 2016;316(4):429-435. 2. grossman dc, curry sj, owens dk, et al. behavioral counseling to prevent skin cancer: us preventive services task force recommendation statement. jama. 2018;319(11):11341142. 3. evidence-based medicine. a new approach to teaching the practice of medicine. jama. 1992;268(17):24202425. 4. berwick m, begg cb, fine ja, roush gc, barnhill rl. screening for cutaneous melanoma by skin self-examination. j natl cancer inst. 1996;88(1):17-23. 5. smith gc, pell jp. parachute use to prevent death and major trauma related to gravitational challenge: systematic review of randomised controlled trials. bmj (clinical research ed). 2003;327(7429):1459-1461. presented at the 13th winter clinical dermatology conference, january 12 –17, 2018, maui, hi, usa an open-label study evaluating the long-term efficacy, quality of life, and safety of lidose-isotretinoin (absorica®) capsules administered without food in patients with severe recalcitrant nodular acne: interim analysis of 20-week active treatment period andrea zaenglein,1 james del rosso2 1department of dermatology, pennsylvania state university, hershey, pa, usa; 2jdr dermatology research/thomas dermatology, las vegas, nv, usa background • severe acne is known to have a significant adverse effect on self-esteem and quality of life (qol).1 effective treatment of acne, with isotretinoin, can subsequently improve the patient’s qol. the timing of qol improvement over the course of treatment with lidose-isotretinoin has not been established • isotretinoin products must be taken with a high-fat meal to achieve optimal absorption. fasted plasma levels of isotretinoin can be nearly 60% lower than fed levels.2 noncompliance with the food intake requirements can potentially compromise the long-term efficacy of isotretinoin3 • absorption of lidose-isotretinoin is less dependent on the amount and/or type of food intake and it can be taken without meals, while still providing a reliable isotretinoin blood concentration4 objective • to evaluate the efficacy and safety of lidose-isotretinoin taken without food by patients with severe recalcitrant nodular acne, in addition to assessing their quality of life – primary objective during the 20-week active treatment period (atp) was to evaluate the qol of patients taking lidose-isotretinoin twice daily (bid) without food – secondary objectives during the atp were to evaluate the efficacy and safety of lidose-isotretinoin taken bid without food methods study design • this is a phase 4, multicenter, single-arm, open-label study conducted in the united states in patients with severe recalcitrant nodular acne (nct02457520, figure 1) consisting of 2 phases: a 20-week (5-month) open-label atp and a 104-week (2-year) post-treatment period study population • key inclusion criteria included: – 12–45 years of age – recalcitrant acne severe enough for isotretinoin treatment, including ≥5 facial nodules – no prior exposure to systemic isotretinoin or other systemic retinoid – weight 40–110 kg – women must not be pregnant and must not be breastfeeding; female patients of childbearing potential must use 2 forms of effective contraception simultaneously for 1 month before trial, during trial, and for 1 month after stopping study medication or commit to continuous abstinence from heterosexual intercourse, and have a negative serum pregnancy test treatment • dosing during 20-week atp to attain target cumulative dose of 120–150 mg/kg: – 0.5 mg/kg/day divided into 2 daily doses for 4 weeks followed by – 1.0 mg/kg/day divided into 2 daily doses for 16 weeks • study medication was taken without food (1 hour before or at least 2 hours after ingestion of food/beverages other than water) endpoints • primary efficacy endpoint was the change from baseline to the end of treatment (eot) in the acne-qol score, assessed on a graded scale (overall and by domain) – domains included self-perception, role-social, role-emotional, and acne symptoms • secondary efficacy endpoints included monthly change from baseline in acne-qol scores (overall and by domain) and lesion counts during the atp and change from baseline to eot in investigator’s global assessment (iga) scores statistical analysis • efficacy evaluation was conducted using the intent-to-treat population • overall acne-qol score, each domain score, and the changes from baseline for these scores were summarized using descriptive statistics. differences between baseline and postbaseline values were analyzed using paired t-tests • descriptive statistics are provided for mean percentage change from baseline value for inflammatory, noninflammatory, and total lesion counts. differences between baseline and postbaseline values were analyzed using paired t-tests • descriptive statistics are provided for iga observed values table 1. baseline demographics all patients enrolled (n=201) gender, n (%) male 125 (62.2) female 76 (37.8) race, n (%) american indian or alaska native 3 (1.5) asian 8 (4.0) black or african american 17 (8.5) multiple 1 (0.5) native hawaiian or other pacific islander 1 (0.5) other 4 (2.0) white 167 (83.1) ethnicity, n (%) hispanic or latino 31 (15.4) age, y mean (sd) 18.7 (6.4) range 12–45 table 2. baseline disease characteristics intent-to-treat population (n=197) number of inflammatory lesions mean (sd) 33.8 (17.0) median (range) 32 (5–108) number of noninflammatory lesions mean (sd) 40.1 (41.3) median (range) 27 (0–250) investigator’s global assessment score mean (sd) 4.1 (0.5) median (range) 4 (3–5) references 1. ritvo e, et al. biopsychosoc med. 2011;5:11–24. 2. colburn wa, et al. j clin pharmacol. 1983;23:534–539. 3. del rosso jq. j clin aesthet dermatol. 2012;5:17–24. 4. webster gf, et al. j am acad dermatol. 2013;69:762–767. acknowledgments editorial support for this poster was provided by anna houlihan of sun pharmaceutical industries, inc., and fishawack communications, funded by sun pharmaceutical industries, inc. statistical support for this poster was provided by novella clinical, funded by sun pharmaceutical industries, inc. lidose-isotretinoin is a retinoid indicated for the treatment of severe recalcitrant nodular acne in patients 12 years of age and older. az and jd consulted on the design and implementation of this clinical trial for sun pharmaceutical industries, inc., who sponsored the study and supported the development of this presentation. disclosures az has served as a consultant for cassiopea and ranbaxy/sun pharmaceutical industries, inc. jd has served as a consultant, speaker, and research investigator for sun pharmaceutical industries, inc. figure 1. study design screening within ≤30 days of baseline visit: weeks: baseline eot eos 2 3 4 5 6 7 8 9 10 11 12 13 141 0 2 4 8 12 16 20 24 32 46 72 98 124 screening period (0–45 days) active treatment period (20 weeks) post-treatment period (104 weeks) eos=end of study; eot=end of treatment. figure 2. patient disposition n=201 enrolled n=170 completed atp n=3 status unknown n=8 ltfu n=8 discontinued owing to ae n=1 protocol deviation n=1 physician decision n=1 other n=6 withdrawal by subject n=3 noncompliance with study drug n=197 itt population (n=4 did not receive study medication) ae=adverse event; atp=active treatment period; itt=intent-to-treat; ltfu=lost to follow-up. figure 3. improvement in acne-qol scores at week 4 and eot 40 30 20 10 0 a cn eq o l s co re , m ea n (s d ) selfperception rolesocial roleemotional acne symptoms 15.8 20.1 26.0 ** ** 15.4 18.0 21.6 ** ** 15.6 20.1 25.6 ** ** 14.6 19.8 25.8 ** ** 120 100 80 60 40 20 0 overall 61.4 77.9 99.0 ** ** baseline (n=197) week 4 (n=166) eot (n=197) eot values reflect the last visit for which a subject had data in the atp. **p≤0.0001. atp=active treatment period; eot=end of treatment; qol=quality of life. figure 5. iga scores over time from baseline to eot 5 4 3 2 1 0 ig a s co re , m ea n (s d ) baseline 4 8 12 weeks 16 20 eot 4.1 3.5 3.1 2.4 1.9 1.1 1.2 eot values reflect the last visit for which a subject had data in the atp. atp=active treatment period; eot=end of treatment; iga=investigator’s global assessment. figure 4. mean change in lesion counts from baseline to eot ** 0 −20 −40 −60 −80 −100 c ha ng e f ro m b as el in e, m ea n, % 4 8 12 weeks 16 20 eot ** ** ** ** ** ******** ** ** ** ** * ** ** ** −83.2 −85.3 −87.2 inflammatory lesions total noninflammatory lesions eot values reflect the last visit for which a subject had data in the atp. differences between postbaseline and baseline values analyzed using paired t-tests. *p=0.0002; **p≤0.0001. atp=active treatment period; eot=end of treatment. conclusions • twice-daily use of lidose-containing isotretinoin taken without food improved patients’ qol over the 20-week treatment period, with improvement seen as early as week 4 • clinical efficacy was also demonstrated • aes were generally consistent with the known safety profile for isotretinoin results disposition • a total of 201 patients (mean age: 18.7 [range: 12–45] years) were enrolled in the study at 21 sites (figure 2) – 85% (170/201) of patients completed the 20-week atp efficacy • there was a significant increase in mean (sd) acne-qol from baseline to eot (61.4 [28.4] vs 99.0 [19.8], p<0.0001). all 4 domains (self-perception, role-social, role-emotional, acne symptoms) were significantly improved over the course of treatment, with positive improvements beginning at week 4 (figure 3) • mean (sd) percentage change in inflammatory (‒87.2 [22.5]) and noninflammatory lesion (‒83.2 [30.3]) counts from baseline to eot were significant (p<0.0001) (figure 4) • mean iga scores improved from baseline by approximately 3.0 points at eot (figure 5) safety • a total of 286 adverse events (aes) was reported in 60.2% of patients (121/201) – the most common aes were dry skin (10.9%), dry lips (10.4%), and cheilitis (9.0%) • a total of 166 treatment-related aes was reported in 46.3% of patients (93/201) – the most commonly reported were dry lips (10.4%), dry skin (10.4%), and cheilitis (9.0%) • twelve severe aes were reported; 5 were considered to be treatment related – nausea (n=2), increased blood cholesterol (n=1), liver function test abnormal (n=1), and headache (n=1) • psychiatric aes occurred in 17 patients (8.5%). the psychiatric events reported in more than 1 patient were depression (4.0%), insomnia (1.0%), and anxiety (1.0%) • abnormal laboratory results occurred in 11 patients (5.5%); those reported in more than 1 patient were blood triglycerides increased (3.5%), increased alanine aminotransferase (1.5%), increased aspartate aminotransferase (1.5%), and blood cholesterol increased (1.5%) • one serious ae was reported: diabetes mellitus on study day 127, severe in intensity and unlikely related to study treatment • eight patients discontinued the study owing to ae – psychiatric events (n=5) and abnormalities in laboratory test results (n=3) – six additional patients had study drug withdrawn for an ae: psychiatric events (n=4), migraine (n=1), and diabetes mellitus (n=1) • baseline demographics and disease characteristics are presented in tables 1 and 2 skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 269 original research pilot study on the effects of natural oils on skin barrier function in xerotic skin alexandra r. vaughn mda,b, mimi nguyen bsa, melody maarouf mhsc, melissa r. van skiver bad, khiem a. tran phdc, iryna rybaka, raja k. sivamani md ms apa,e,f, vivian y. shi mdd adepartment of dermatology, university of california – davis, sacramento, ca bdrexel university college of medicine, philadelphia, pa cuniversity of arizona college of medicine, tucson, az ddepartment of medicine, division of dermatology, university of arizona, tucson, az edepartment of biological sciences, california state university, sacramento, ca fpacific skin institute, sacramento, ca xerosis is associated with disrupted stratum corneum (sc) integrity and skin barrier function (sbf), leading to decreased hydration and transepidermal water loss (tewl).1 there is a growing trend towards using alternative natural moisturizers, as barrier repair emollients are expensive and often contain potential irritants and allergens. white petrolatum (wp) is a commonly recommended moisturizer, but compliance is often limited by its greasiness. introduction objective: to compare the effect of natural oils and white petrolatum on skin barrier function in patients with xerosis. design, setting, and participants: randomized, open label, comparison pilot study (nct03093597). interventions: participants were randomized to apply 1 of 4 moisturizers to assigned treatment areas twice daily for 2 weeks. clinical dry skin score, stratum corneum hydration, and transepidermal water loss (tewl) were assessed at baseline, 1 week, and 2 weeks. results: thirty-two participants completed the study. neither tewl nor hydration were statistically different among the moisturizers at each visit. all four moisturizers led to significant initial increase in tewl at week 1 (p < 0.05) with an associated increase in hydration for coconut oil, jojoba oil, and white petrolatum. all four moisturizers led to significant increase in hydration by week 2 (p < 0.01). the preferred moisturizers were almond oil and coconut oil, which were most “liked” by 38% and 31% of the participants, respectively. the least preferred moisturizer was white petrolatum. conclusions: almond oil, jojoba oil, and coconut oil significantly increased hydration after 2 weeks, and are as effective as white petrolatum as daily moisturizers for xerosis. the participants preferred natural oils to white petrolatum, implying that these moisturizer options may improve patient compliance. abstract skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 270 the fatty acid composition of natural oils contributes to their unique characteristics and effects on the skin; for instance olive oil is higher in oleic acid and appears to disrupt the skin barrier, while oils higher in linoleic acid appear to improve the skin barrier.2 coconut oil (co) is comparable to mineral oil at improving hydration without altering tewl and has anti-microbial properties.3 jojoba oil (jo) can decrease tewl and enhance sc moisturization.4 almond oil (ao) is rich in antioxidants such as omega and linoleic fatty acids and vitamin e and has occlusive properties comparable to mineral oil.5 there is no head-to-head comparison between natural oils and wp for moisturization. this randomized, open label, comparison pilot study aims to compare the ability of natural oils (ao, co, and jo) and wp to improve xerosis and sbf. this clinical trial was registered on clinicaltrials.gov (nct03093597) prior to participant enrollment. nineteen subjects from university of california, davis (ucd) in sacramento and eighteen subjects from university of arizona (az) in tucson participated in this study (mean age 59.5 years old, range 24-85 years). the study was approved by the institutional review board at both sites, and time period for recruitment and follow-up was january 18, 2017 through july 31, 2017. baseline tewl and hydration were not significantly different. subjects were supplied with pre-measured certified organic co (nature’s bounty®), jo (the jojoba company), ao (mountain rose herbs), and wp. each of the four moisturizers was pre-randomized in blinded envelopes to one of four application areas on the right and left forearms prior to recruitment. the subjects applied 0.1ml of each moisturizer twice daily to the assigned area for two weeks. tewl and hydration were measured at baseline, 1 week and 2 weeks using vapometer and moisturemetersc (delfin technologies), respectively. xerosis was graded using the dry skin scale (dss)6, and ucd participants were asked to complete a survey regarding moisturizer preferences at the final visit. intraand intergroup evaluations were performed using paired t-test and a bonferroni correction was implemented to reduce type i error when comparing moisturizers. four subjects were lost to follow-up after the baseline visit, one subject dropped out after week 1 due to scheduling conflicts, and thirtytwo subjects completed the week 2 study visit. outcome measurements are displayed in figure 1. neither the tewl nor the hydration were statistically different among moisturizers at each visit. all moisturizers significantly increased tewl at week 1 (p < 0.05) compared to baseline, and only jo and co persisted to have a significant increase in tewl at week 2 (p < 0.05). all four moisturizers significantly increased in hydration by week 2 (p < 0.01). there were no significant differences in outcome measurements when data was analyzed separately for each study site. thirteen participants at the ucd study site completed a survey, and ao was most “liked” (38%), followed by co (31%). wp was “least liked” (62%). no adverse events were reported. methods results skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 271 figure 1. changes in skin barrier biophysical properties with moisturizer use. transepidermal water loss (a) and hydration (b) values at week 1 and week 2 visits are normalized to the measurements at the baseline visit. error bars represent sem. n=32. * = p<0.01. ao, jo, and co can be as effective as wp in improving sbf in patients with xerosis. limitations of this study include: assessments localized to forearms, short study period, and relatively low baseline dss in study subjects. natural oils can be comparable alternatives to commercially available emollients and are preferred over wp, which may improve patient compliance. antimicrobial, antioxidant, and antiinflammatory properties are additional benefits of natural oils. larger randomized trails that evaluate the benefit of additional natural oils are needed, especially in inflammatory dermatoses associated with barrier defects, such as atopic dermatitis and psoriasis. conflict of interest disclosures: rks serves as a scientific advisor to dermveda and serves as a consultant to dermala and burt’s bees. vys has stock options in dermveda, serves as a consultant for menlo therapeutics, sanofi genzyme, burt’s bees, and the national eczema association, and has received research funding from skin actives scientific. funding: arv received a medical student research grant from banyan botanicals. the funding source had no role in data analysis or the decision for publication. corresponding author: vivian y. shi, md department of medicine, dermatology division university of arizona vshi@email.arizona.edu references: 1. kezic s, novak n, jakasa i, jungersted jm, simon m, brandner jm, et al. skin barrier in atopic dermatitis. frontiers in bioscience (landmark edition). 2014;19:542-56. 2. vaughn ar, clark ak, sivamani rk, shi vy. natural oils for skin-barrier repair: ancient compounds now backed by modern science. am j clin dermatol. 2018;19(1):103-17. 3. agero al, verallo-rowell vm. a randomized double-blind controlled trial comparing extra virgin coconut oil with mineral oil as a moisturizer for mild to moderate xerosis. dermatitis : contact, atopic, occupational, drug. 2004;15(3):109-16. 4. meyer j, marshall b, gacula m, jr., rheins l. evaluation of additive effects of hydrolyzed jojoba (simmondsia chinensis) esters and glycerol: a preliminary study. journal of cosmetic dermatology. 2008;7(4):268-74. 5. ranzato e, martinotti s, burlando b. wound healing properties of jojoba liquid wax: an in vitro study. journal of discussion mailto:vshi@email.arizona.edu skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 272 ethnopharmacology. 2011;134(2):4439. 6. serup j. eemco guidance for the assessment of dry skin (xerosis) and ichthyosis: clinical scoring systems. skin research and technology: official journal of international society for bioengineering and the skin (isbs) [and] international society for digital imaging of skin (isdis) [and] international society for skin imaging (issi). 1995;1(3):109-14. fc20 poster kirsch cl106 = brandon kirsch, md1, danielle armas, md2, deepak chadha, ms, mba, rac3 1kirsch dermatology, naples, fl, 2celerion, inc., tempe, az, 3brickell biotech, inc., boulder, co a four-way, cross-over design, randomized, double-blinded, placeboand active-controlled study for the evaluation of the effect of a supratherapeutic dose of sofpironium bromide gel, 15% applied topically on the qt/qtc intervals in adult healthy volunteers (bbi-4000-cl-106) sofpironium bromide is a retro-metabolically designed analog of glycopyrrolate (anticholinergic) in development for the topical treatment of primary axillary hyperhidrosis. cardiac safety can be a major factor in clinical development given the potential effect of new drugs in delaying cardiac repolarization. in a study designed to mimic exposure that may occur under extreme circumstances in healthy subjects (bbi-4000-cl-109), a single 6-fold application of sofpironium bromide gel, 15% under occlusion showed a 3-fold increase in maximum sofpironium exposure compared to the intended therapeutic dose. • a topical ~173 mg total dose of sofpironium bromide gel, 15% (intended therapeutic dose) without occlusion to the axillae (t), or • a topical ~1038 mg total dose of sofpironium bromide gel, 15% (supratherapeutic dose) with occlusion that was 6-fold higher than the intended therapeutic dose to the axillae, lateral side of the upper arms, ventral side of the thighs, and central abdomen (st), or • a topical dose of placebo gel with occlusion applied to the same sites as those used for the supratherapeutic and intended therapeutic doses (p), or • an oral dose of moxifloxacin (400 mg) (m). there was a washout period of at least 7 days between the dosing periods. administration of ~1038 mg sofpironium bromide gel, 15% (occluded) resulted in a 3.2-fold increase in cmax compared to the ~173 mg dose of sofpironium bromide gel, 15% (unoccluded). mean placebo-corrected change-from-baseline qtcf (δδqtcf) ranged from -3.5 ms on the supratherapeutic treatment at 10.5 hr postdose to +3.3 ms on the therapeutic treatment at 1 hr post-dose. an effect on δδqtcf exceeding 10 ms could be excluded with both sofpironium bromide gel, 15% doses, since the upper bound of the 90% ci was below 10 ms at all post-dose time points. assay sensitivity was demonstrated by oral dosing with 400 mg of positive control, moxifloxacin. the study constitutes a negative tqt study, as defined in ich e14 clinical guidance. systemic exposure increased more than 3-fold following supratherapeutic dosing under occlusion, but no clinically relevant changes in the qtc interval, heart rate, or cardiac conduction were noted. therapeutic (unoccluded) and supratherapeutic (occluded, 6fold) doses of sofpironium bromide gel, 15% appeared to be safe and generally well tolerated. brickell biotech, inc. supported the study and preparation of this abstract. funding statement conclusion background methods academic poster presented at the 2020 fall clinical dermatology conference | las vegas, nv | october 29 november 1, 2020 objective the prospective effect of a drug on cardiac repolarization can be measured as prolongation of the qt interval on electrocardiographic recordings. the primary objective of this thorough qt (tqt) study was to evaluate the effect of a single supratherapeutic dose (6-fold) of sofpironium bromide gel, 15% under occlusion on the fridericiacorrected qt interval (qtcf). 0 0. 5 1 1. 5 2 2. 5 3 3. 5 pr ed os e .5 h 1 h 2 h 3 h 4 h 6 h 8 h 9 h 10 .5 h 12 h 16 h 24 h p la sm a s o fp ir o n iu m c o n ce n tr a ti o n ( n g /m l) sample collection hour t re atm e n t st : 1 0 38 m g sofpi roni u m brom i de ge l , 1 5% (6 x th er ape u ti c dose , occ l ude d) t re atm e n t t: 1 7 3 m g sofpi ron i um brom ide ge l, 1 5 % pl u s pl a ce bo gel (u noc cl u de d) figure 1: mean plasma concentration of sofpironium1 treatment adverse events t st p m total number of subjects dosed 59 (100%) 60 (100%) 60 (100%) 58 (100%) 60 (100%) number of subjects with teaes 17 (29%) 43 (72%) 54 (90%) 12 (21%) 57 (95%) number of subjects without teaes 42 (71%) 17 (28%) 6 (10%) 46 (79%) 3 (5%) application site erythema 3 (5%) 28 (47%) 41 (68%) 0 (0%) 47 (78%) application site pain 2 (3%) 18 (30%) 22 (37%) 0 (0%) 33 (55%) application site pruritis 1 (2%) 18 (30%) 17 (28%) 0 (0%) 28 (47%) application site exfoliation 7 (12%) 8 (13%) 2 (3%) 0 (0%) 14 (23%) headache 2 (3%) 3 (5%) 3 (5%) 2 (3%) 9 (15%) dermatitis contact 2 (3%) 0 (0%) 1 (2%) 1 (2%) 3 (5%) oropharyngeal pain 0 (0%) 2 (3%) 0 (0%) 1 (2%) 3 (5%) pruritus 0 (0%) 2 (3%) 1 (2%) 0 (0%) 3 (5%) upper respiratory tract infection 0 (0%) 2 (3%) 1 (2%) 0 (0%) 3 (5%) vision blurred 1 (2%) 2 (3%) 0 (0%) 0 (0%) 3 (5%) table 1: adverse event frequency by treatment – number of subjects reporting the event (% of subjects dosed) (safety population) (≥5%) results this was a randomized, double-blind (with respect to the supratherapeutic dose (6-fold) of sofpironium bromide gel, 15% and placebo gel only) and active-controlled (with respect to the moxifloxacin and therapeutic dose of sofpironium bromide gel, 15%), single-dose, 4-way crossover tqt study. sixty healthy adult male and female subjects were enrolled. on day 1 of each period, subjects aged ≥18 to ≤55 years received one of the following investigational treatments: figure 2: placebo-corrected change-from-baseline qtcf across time points -5 0 5 10 15 20 0. 5 1 2 3 4 6 8 9 10 .5 12 16 24 δ δ q t cf ( m s) hours post-dose tr eat m ent t tr eat m ent st m oxif loxac in overall efficacy at 42 months • clinically relevant objective response rates (orrs) continued to be reported for patients receiving 200 mg/day of sonidegib at 42 months (table 2) • at 42 months, the orr (95% confidence interval) was 48.1% (36.7%–59.6%) for all 79 patients receiving 200 mg/d of sonidegib • disease control rate exceeded 90% and further supports treatment benefit (table 2) • sustained duration was confirmed, with a median duration of response of 26.1 months (table 2) table 2. efficacy outcomes per central review in patients with advanced bcc receiving sonidegib 200 mg daily iabcc (n = 66) mbcc (n = 13) orr, % (95% ci) 56.1 (43.3, 68.3) 7.7 (0.2, 36.0) cr, % (95% ci) 4.5 (0.9, 12.7) 0 (0.0, 24.7) dcr, % 90.9 92.3 dor, median, months (95% ci) 26.1 (ne) 24.0 (ne) pfs, median, months (95% ci) 22.1 (ne) 13.1 (5.6, 33.1) ttr, median, months (95% ci) 4.0 (3.8, 5.6) 9.2 (ne) bcc, basal cell carcinoma; ci, confidence interval; cr, complete response; dcr, disease control rate; dor, duration of response; labcc, locally advanced bcc; mbcc, metastatic bcc; ne, not estimable; orr, objective response rate; pfs, progression-free survival; ttr, time to tumor response. overall safety/tolerability at 42 months • median duration of sonidegib exposure was 11.0 months in the 200 mg/day group • overall, 54 (68.4%), 34 (43.0%), and 19 (24.1%) patients were exposed to sonidegib 200 mg/day for ≥8, ≥12, and ≥20 months, respectively • the majority of aes were grade 1−2 in severity • the most common all-grade aes in patients receiving sonidegib 200 mg/day were muscle spasms (54.4%, n = 43), alopecia (49.4%, n = 39), dysgeusia (44.3%, n = 35), nausea (39.3%, n = 31), fatigue (33.0%, n = 26), diarrhea (31.7%, n = 25), weight decrease (30.5%, n = 24), and creatine kinase (ck) increase (30.4%, n = 24) (figure 4) figure 4. adverse events reported in ≥30% of patients receiving 200 mg daily n = 79. ae, adverse event; ck, creatine kinase. background • sonidegib—a hedgehog inhibitor (hhi) that selectively targets smoothened1—is approved in the us, the eu, and australia for the treatment of adult patients with locally advanced basal cell carcinoma (labcc) not amenable to curative surgery or radiation therapy1-4 — sonidegib is also approved for the treatment of metastatic bcc (mbcc) in switzerland and australia3,4 • through 42 months of the phase 2 bolt (basal cell carcinoma outcomes with lde225 [sonidegib] treatment) trial (nct01327053), sonidegib 200 mg/day demonstrated durable efficacy and consistent/manageable toxicity5-9 objectives • here, we report the incidence and impact of hhi class-effect adverse events (aes) from the bolt 42-month results methods • bolt was a randomized, double-blind, phase 2 clinical trial conducted in 58 centers across 12 countries5 (figure 1) adverse events of special interest in patients with advanced basal cell carcinoma receiving sonidegib: long-term 42-month results from the bolt study alexander guminski,1,2 nicholas squittieri,3 john t lear4 1royal north shore hospital, st leonards, nsw, australia; 2university of sydney, sydney, australia; 3sun pharmaceutical industries, inc., princeton, nj, usa; 4manchester academic health science centre, university of manchester, manchester, uk figure 1. bolt study design apatients previously treated with sonidegib or other hhi were excluded. bstratification was based on stage, disease histology for patients with labcc (nonaggressive vs aggressive), and geographic region. ctreatment was continued until disease progression, unacceptable toxicity, death, study termination, or withdrawal of consent. ae, adverse event; bcc, basal cell carcinoma; bolt, basal cell carcinoma outcomes with lde225 (sonidegib) treatment; cr, complete response; dor, duration of response; hhi, hedgehog inhibitor; labcc, locally advanced bcc; mbcc, metastatic bcc; mrecist, modified response evaluation criteria in solid tumors; orr, objective response rate; os, overall survival; pfs, progression-free survival; q8w, every 8 weeks; q12w, every 12 weeks; ttr, time to tumor response. • safety/tolerability were assessed through monitoring and recording aes; regular monitoring of hematology, clinical chemistry, and electrocardiograms; and routine monitoring of vital signs and physical condition — aes were coded using the medical dictionary for regulatory activities terminology v19.0 and toxicity was assessed using the national cancer institute common terminology criteria for adverse events v4.0312 — muscle-related events were evaluated by an independent safety review and adjudication committee — aes of special interest for hhi-class drugs included muscle-related events, alopecia, nausea and/or vomiting, dysgeusia, decreased appetite and/or weight loss, fatigue/lethargy, diarrhea, hypersensitivity, second primary malignancies, qt prolongation, lipase and amylase elevations, fractures, and cardiac disorders • dose modifications were based on the worst grade of toxicity observed • dose delays of ≤21 days and dose reductions were permitted for aes suspected to be related to sonidegib • data presented here are based on the us food and drug administration-approved 200-mg dose at 42 months results • at baseline, 60.8% of the 79 patients receiving sonidegib 200 mg/day were male and had a median age of 67.0 years; the majority (83.5%) of patients had labcc and 62.0% had ≥2 lesions (table 1) table 1. baseline demographics and disease characteristics in patients receiving sonidegib 200 mg daily sonidegib 200 mg (n = 79) median age (range), years 67 (25–92) male 48 (61) ecog performance status 0 1 2 unknown 50 (63) 19 (24) 8 (10) 2 (3) stage labcc mbcc 66 (84) 13 (16) histologic/cytologic subtype aggressivea nonaggressiveb undetermined 40 (51) 38 (48) 1 (1) number of lesions 1 ≥2 30 (38) 49 (62) metastasis sites lung bone axillary lymph node trunk otherc 14 (18) 10/14 (71) 2/14 (14) 1/14 (7) 1/14 (7) 3/14 (21) prior antineoplastic therapy surgery radiotherapy 59 (75) 19 (24) data presented as n (%) unless otherwise indicated. aincludes micronodular, infiltrative, multifocal, basosquamous, and sclerosing histological subtypes. bincludes nodular and superficial histological subtypes.cincludes retroorbital and left mandible, pelvic side wall and lung, and bilateral scalp. bcc, basal cell carcinoma; ecog, eastern cooperative oncology group; labcc, locally advanced bcc; mbcc, metastatic bcc. • muscle-related events leading to discontinuation were grade 2 muscle spasms (n = 1), grade 3 muscle spasms (n = 3), and grade 3 blood ck increase (n = 1). the event requiring dose adjustment was muscle weakness • fatigue and asthenia events leading to discontinuation were grade 3 asthenia (n = 1), grade 2 asthenia (n = 2), and grade 1/2 fatigue (n = 2); there were no lethargy events leading to discontinuation • decreased appetite and weight loss events leading to discontinuation were grade 1/2 decreased appetite (n = 2) and grade 2 weight loss (n = 2) • no new second primary malignancies were reported at 42 months in patients receiving sonidegib 200 mg/day. the 2 events leading to discontinuation were grade 3 invasive papillary breast carcinoma and grade 2 prostate cancer; both were determined not related to the study drug conclusions • patients receiving sonidegib 200 mg/day experienced consistent and robust efficacy and manageable tolerability, with rare grade 3/4 aes and discontinuations • safety and tolerability of sonidegib 200 mg/day at 42 months was consistent with earlier data • aes of special interest associated with hhi-class drugs were manageable and few led to discontinuations or dose reductions in patients receiving sonidegib 200 mg/day references 1. migden mr, et al. lancet oncol. 2015;16(6):716–28. 2. odomzo (sonidegib) [package insert]. cranbury, nj: sun pharmaceutical industries, inc.; 2017. 3. australian government department of health, artg 292262. 4. european medicines agency. summary of product characteristics, wc500188762. 5. swissmedic, authorization number 65065, 2015. 6. migden mr, et al. j clin oncol. 2018; 36: suppl abstr 9551. 7. lear jt, et al. j eur acad dermatol venereol. 2018; 32 (3): 372–81. 8. dummer r, et al. j am acad dermatol. 2016; 75 (1): 113–25 e5. 9. dummer r, et al. br j dermatol. 2019; 10.1111/bjd.18552. 10. eisenhauer ea, et al. eur j cancer. 2009; 45 (2): 228–47. 11. world health organization. http://whqlibdoc.who.int/offset/who_offset_48.pdf. 12. national cancer institute. common terminology criteria for adverse events v4.03. acknowledgments medical writing and editorial support provided by jennifer meyering, rn, ms, ccmp, of alphabiocom, llc, and funded by sun pharmaceutical industries, inc. disclosures ag has participated on advisory boards for bristol-myers squibb, pfizer, and sanofi; received honoraria from novartis pharmaceuticals corporation; and received travel support from astellas and bristol-myers squibb. ns is an employee of sun pharmaceutical industries, inc. jtl has served as a consultant for novartis and received personal fees from sun pharmaceutical industries, inc. figure 2. bolt study endpoints bcc, basal cell carcinoma; bolt, basal cell carcinoma outcomes with lde225 (sonidegib) treatment; cr, complete response; dor, duration of response; labcc, locally advanced bcc; mbcc, metastatic bcc; mrecist, modified response evaluation criteria in solid tumors; orr, objective response rate; os, overall survival; pfs, progression-free survival; pr, partial response; ttr, time to tumor response. • of all 79 patients receiving sonidegib 200 mg/day, 16.5% of patients (n = 13) had a dose reduction and 68.4% (n = 54) had ≥1 dose interruption; 44.3% (n = 35) had ≥2 dose interruptions • most aes of special interest were of grade <3. the most common grade 3/4 aes of special interest (occurred in ≥5%) were increased ck (6.3%, n = 5); weight loss (5.1%, n = 4); lipase and amylase elevations (6.3%, n = 5); nausea and/or vomiting and their complications (5.1%, n = 4); and fatigue and asthenia (5.1%, n = 4) — the majority of high-grade aes were reversible with interruptions in treatment — the time-to-first onset of grade 3/4 muscle-related events ranged from 1.9 to 11.0 months in patients receiving sonidegib 200 mg/day • few aes of special interest required discontinuation of sonidegib or reductions in dose (table 3) table 3. adverse events of special interest leading to discontinuation or dose adjustments in patients receiving sonidegib 200 mg daily adverse event leading to discontinuation requiring dose adjustment muscle-related events 5 (6.3) 1 (1.3) fatigue and asthenia 5 (6.3) 1 (1.3) decreased appetite and/or weight loss 4 (5.1) 0 dysgeusia 3 (3.8) 1 (1.3) nausea and/or vomiting 3 (3.8) 0 second primary malignancies 2 (2.5) 0 increased lipase 2 (2.5) 3 (3.8) alopecia 1 (1.3) 1 (1.3) hypersensitivity 1 (1.3) 0 fractures 1 (1.3) 0 cardiac disorders 0 0 n = 79. data are presented as n (%). • eligible patients had either histologically confirmed labcc (not amenable to curative surgery or radiation) or mbcc (for which all other treatment options had been exhausted) • primary and secondary endpoints are summarized in figure 2 orr→ best overall confirmed response of cr or pr per central review according to mrecist (labcc) or recist v1.1 (mbcc)primary dor and cr rates per central review according to mrecist (labcc) or recist v1.1 (mbcc) key secondary • os • safety other secondary • orr and dor per investigator review • pfs and ttr per central and investigator review figure 3. tumor evaluation per mrecist (labcc) mrecist is a composite multimodal evaluation used to integrate mri according to recist v1.1,10 standard and annotated color photography using bidimensional who criteria,11 and histology in multiple biopsies based on lesion surface area in the complex setting of posttreatment scarring, fibrosis, and illdefined lesion borders. complete response is defined as a negative mri, negative photo, and negative histology. partial response is defined as ≥50% reduction in bidimensional format. bcc, basal cell carcinoma; labcc, locally advanced bcc; mrecist, modified response evaluation criteria in solid tumors; mri, magnetic resonance imaging; who, world health organization. + + composite overall response per mrecist mri per recist v1.1 histologyphoto per who criteria • tumor response was evaluated by investigator review and by central review using modified response evaluation criteria in solid tumors (mrecist) for patients with labcc and recist v1.1 for patients with mbcc (figure 2 and figure 3) follow-up (after treatment discontinuation) • tumor response q8w during year 1 and then q12w until progression • subsequent anticancer therapy • aes until 30 days after last dose of sonidegib • survival follow-up q12w until death, lost to follow-up, or withdrawn consent (and at time of final analysis) endpoints primary: orr (central review) by mrecist (labcc) or recist v1.1 (mbcc) key secondary: dor, cr (central review) other secondary: orr, dor (investigator review); pfs, ttr (central and investigator review); os, safety stratificationb randomization (1:2) sonidegib 200 mg dailyc sonidegib 800 mg dailyc patient populationa • labcc (aggressive and nonaggressive) • mbcc adverse events of special interest at 42 months • incidence and severity of hhi class-effect aes at 42 months were consistent with reports at 30 months • the most common all-grade aes of special interest in patients receiving sonidegib 200 mg/day (n = 79) were all muscle-related events (68.4%); muscle spasms (54.4%); alopecia (49.4%); dysgeusia (44.3%); and nausea (39.2%) (figure 5) figure 5. adverse events of special interest reported in ≥30% of patients receiving sonidegib 200 mg daily n = 79. ae, adverse event; ck, creatine kinase. 25.4 24.1 30.4 31.7 38.0 44.3 49.4 51.9 5.1 6.3 1.3 1.3 1.3 0 0 2.5 0 10 20 30 40 50 60 weight decrease ck increase diarrhea fatigue nausea dysgeusia alopecia muscle spasms grade <3 grade 3-4 patients reporting aes (%) ck increased weight decreased diarrhea fatigue nausea dysgeusia alopecia muscle spasm patients reporting aes (%) grade 3–4 grade 1–2 51.9 49.4 44.3 38.0 31.6 30.4 25.3 24.1 2.5 0 0 1.3 1.3 1.3 5.1 6.3 10 20 30 40 50 600 presented at fall clinical dermatology conference for pas & nps 2020, april 3–5, orlando, fl, usa skin may 2019 volume 3 issue 3 copyright 2018 the national society for cutaneous medicine 226 short communications crohn's disease presenting as isolated lower lip swelling anna-marie hosking bs1, lance chapman md mba1, janellen smith md1 1department of dermatology, university of california irvine, irvine, ca a woman in her late 20s presented with a 6month history of lower lip swelling and painful oral mucosal lesions. history was significant for asthma, bipolar disorder, headaches, and a history of gastrointestinal disease (records were requested to verify a diagnosis). medications included albuterol, quetiapine, lamotrigine, and ibuprofen. review of systems was significant for occasional abdominal cramping. there was no family history of similar facial swelling. clinical examination revealed lower lip edema, cheilitis, and two oral aphthous ulcerations without evidence of facial palsy (figure 1). laboratory evaluation revealed negative antinuclear, anti-double-stranded dna, antismith, anti-ribonucleoprotein, anti-scl-70, anti-ssa, and anti-ssb antibodies. c1 esterase inhibitor was 34 mg/dl (ref 21-39 mg/dl), functional c1 inhibitor was 100% (normal >68%), c3 was 116 mg/dl (ref 90180 mg/dl), and c4 was 27 mg/dl (ref 16-47 mg/dl). c-reactive protein (crp) was 0.70 (ref 0-0.70 mg/dl) and erythrocyte sedimentation rate (esr) was 16 mm/h (ref 0-20 mm/h). angiotensin-converting enzyme (ace) was 62 u/l (ref 9-67 u/l) and vitamin d was 25 ng/ml (ref 30-150 ng/ml). quantiferon gold was negative. a punch biopsy of the inner lower lip demonstrated an inflammatory infiltrate of lymphocytes and plasma cells with noncaseating collections of histiocytes, consistent with granulomas (figure 2). no refractile material was identified under polarized light. outside records verified a diagnosis of crohn’s disease as identified on endoscopy/colonoscopy at age 16. at that time, she was treated with corticosteroids for four years with subsequent remission and no further follow up. figure 1. initial clinical presentation of crohn’s disease with lower lip protrusion and edema. case report skin may 2019 volume 3 issue 3 copyright 2018 the national society for cutaneous medicine 227 we attempted treatment with intralesional corticosteroids, however, the patient tolerated less than 1cc of 5 mg/cc triamcinolone and declined further treatment secondary to pain. she was referred to gastroenterology for endoscopy and colonoscopy; no active crohn’s disease was identified. first described by dudeney et al. in 1969, the oral manifestations of crohn’s disease include specific findings: cobblestoning, labial and buccal swelling with vertical fissures, mucosal tags, and granulomatous cheilitis, as well as non-specific findings: aphthous ulceration and angular cheilitis.1–3 in a study of 228 oral crohn’s lesions, lip involvement was the most common (57), followed by gingiva (40), vestibular sulci (31), and buccal mucosa (25).3 in rare cases, oral manifestations may be the initial and/or only presentation of disease.4 histologically, crohn’s disease presents with non-necrotizing granulomatous inflammation. differential diagnosis includes sarcoidosis, foreign body reaction, and infections such as tuberculosis, cat-scratch disease, histoplasmosis, etc.5 miescher cheilitis and melkersson-rosenthal syndrome are other key differential diagnoses presenting with idiopathic lip edema, induration, angular cheilitis, and granulomatous inflammation. melkerssonrosenthal syndrome also presents with facial palsy, unilateral edema, and tongue fissures. additional pathologies can present with lip edema without granuloma formation, including drug-induced angioedema, c1 esterase inhibitor deficiency, and dietary allergies, including cinnamon and benzoate.6 treatment depends on disease location and severity; thus, endoscopic evaluation is figure 2. histopathological analysis of punch biopsy specimen of the left lower lip showing non-necrotizing granulomatous inflammation, consistent with crohn’s disease (original magnification x 20). warranted. however, oral manifestations may occur in the absence of lower gastrointestinal disease. for isolated oral crohn’s disease, treatment includes topical corticosteroids or tacrolimus, corticosteroid mouthwashes, or intralesional corticosteroids. systemic treatment with corticosteroids or azathioprine can be used when topical treatments fail, though in this modern era one might consider one of the newer biologic agents. conflict of interest disclosures: none. funding: none. acknowledgements: we are indebted to ronald m. harris, md, department of dermatology at the university of california irvine medical center, for his valued contribution with the histopathology. corresponding author: anna-marie hosking, bs university of california irvine irvine, ca ahosking@uci.edu references: 1. dudeney tp. crohn’s disease of the mouth. proc r soc med. 1969;62(12):1237. 2. tan cxw, brand hs, de boer nkh, forouzanfar t. gastrointestinal diseases discussion mailto:ahosking@uci.edu skin may 2019 volume 3 issue 3 copyright 2018 the national society for cutaneous medicine 228 and their oro-dental manifestations: part 1: crohn’s disease. br dent j. 2016;221(12):794-799. doi:10.1038/sj.bdj.2016.954 3. plauth mmd, jenss hmd, meyle jmd. oral manifestations of crohn’s disease: an analysis of 79 cases. j clin gastroenterol. 1991;13(1):29-37. 4. harikishan g, reddy nr, prasad h, anitha s. oral crohn’s disease without intestinal manifestations. j pharm bioallied sci. 2012;4(suppl 2):s431-s434. doi:10.4103/0975-7406.100322 5. alawi f. granulomatous diseases of the oral tissues: differential diagnosis and update. dent clin north am. 2005;49(1):203-221. doi:10.1016/j.cden.2004.07.012 6. campbell he, escudier mp, patel p, challacombe sj, sanderson jd, lomer mce. review article: cinnamonand benzoatefree diet as a primary treatment for orofacial granulomatosis. aliment pharmacol ther. 2011;34(7):687-701. doi:10.1111/j.1365-2036.2011.04792.x skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 29 rising derm stars® abstracts the ongoing impact of covid-19 on us dermatology practices graham h litchman do, ms1, justin w. marson, md2, darrell s. rigel, md, ms3 1department of dermatology, st. john’s episcopal hospital, far rockaway, ny 2national society for cutaneous medicine, new york, ny 3department of dermatology, nyu grossman school of medicine, new york, ny covid-19 is significantly impacting healthcare delivery worldwide.1 chen et al anecdotally reported the impact on dermatology outpatient care at the outbreak epicenter in wuhan, china, but nothing has yet been assessed for the us.2 the purpose of this study was to determine the magnitude of the ongoing impact of covid19 on us dermatology outpatient care. after pre-validation, 2 surveys comparing outpatient volumes and scheduling issues for the weeks of february 17th versus the week of march 16th, 2020 (survey 1) and april 13th, 2020 (survey 2) and for estimation of trends in the next several weeks was emailed to 9,891 us dermatologists on 3/21 (survey 1) and 4/18 (survey 2). because of the importance of this information and the need for rapid dissemination, only data from the first 1,000 respondents (collected in the initial 36 hours) were included in each survey. in survey 1, 30 responses were removed due to ineligible geography or errors in survey entry, leaving 970 for the analysis. survey 2 consisted of 1,000 eligible respondents. demographics (table 1) representativeness with aad membership was confirmed (table 2). statistical significance was calculated using chi-square, difference-of-proportions, and two-tailed independent t-tests. covid-19 impact was material (table 3). from the 3rd week in february to the 3rd week in march to the 3rd week in april, the average number of patients seen fell from 149.4 to 63.4 to 28.2(p<0.0001), practice days from 4.2 to 3.1 and then rose to 3.5(p<0.0001) and biopsies from 19.8 to 7.7 to 3.5(p<0.0001). although by 3/16 there were only 24.5k cases nationally3, the earlyphase decrease in patient volume and office days suggests the magnitude of disease concern impact was greater than actual prevalence. postponement of non-essential appointments increased from 35.5% to 79.4% to 95.6%(p<0.0001). in survey 1, 66.3% of respondents estimated a >50% decrease in patient volume in the coming 2 weeks (18.9% completely closing practices) and, disturbingly, 47.2% of respondents in the 2nd survey estimated an additional ≥50% decrease in patient volume in the next 2 weeks. 54.6% (survey 1) of postponed appointments were for >4 weeks with an additional 25.4% not rescheduled. introduction methods results skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 30 table 1. participant demographics by survey versus aad us membership data. demographics (n=1000) survey 1 (%, 95% ci) survey 2 (%, 95% ci) survey 3 (%, 95% ci) aad us membership* practice type private 89.1 (87.1-91.1) 89.7 (87.8-91.6) 89.7 87.6-91.8) university/academic/ government 10.9 (8.9-12.9) 10.3 (8.4-12.2) 10.3 (8.2-12.4) years of experience 1-10 21.8 (19.1-24.5) 18.9 (16.4-21.4) 16.1 (13.6-18.6) 27.0% 11-20 26.6 (23.8-29.4) 25.7 (22.9-28.5) 22.3 (19.4-25.2) 27.5% 21-30 26.3 (23.5-29.1) 29.3 (26.4-32.2) 29.8 (26.6-33.0) 21.8% > 30 25.4 (22.6-28.2) 26.1 (23.3-28.9) 31.7 (28.5-34.9) 23.7% practice mix aad practice profile, 2017** medical 63.0 (59.9-66.1) 60.4 (57.3-63.5) 61.5 (58.1-64.9) 63% surgical/oncology 26.7 (23.9-29.5) 25.8 (23.0-28.6) 23.2 (20.3-26.1) 25% cosmetic 14.8 (12.5-17.1) 11.5 (9.5-13.5) 12.9 (10.6-15.2) 12% dermatopathology 4.4 (3.1-5.7) 2.4 (1.4-3.4) 2.4 (1.3-3.5) *source: american academy of dermatology. practices mix/types not available. **source: margosian e. medical vs. cosmetic dermatology: who is doing what?. dermatology world.2019. http://digitaleditions.walsworthprintgroup.com/publication/?m=12468&i=552514&view=articlebrowser&article_id=3267519&search=practice%20p rofile&ver=html5. no data available for dermatopathology. table 2. geographic and practice tenure distribution of survey respondents versus american academy of dermatology us membership 1stdigit zip (region) code aad us membership (%) 9.6% 12.8% 10.3% 13.8% 8.3% survey 1 (%) 9.4% 14.0% 11.0% 12.3% 7.6% survey 2 (%) 8.4% 15.8% 10.9% 12.4% 8.6% 1stdigit zip (region) code aad us membership (%) 4.8% 6.5% 10.0% 6.1% 17.1% survey 1 (%) 3.9% 6.6% 10.0% 8.4% 16.3% survey 2 (%) 4.2% 6.2% 8.7% 7.7% 16.5% skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 31 table 3. comparison of us dermatology practice during february 17-21 versus march 16-20, april 13-18, and prospective practice estimates. week of february 17, 2020 week of march 16, 2020 week of april 13, 2020 p-value how many days did you practice? (mean; 95%ci) 4.18 (4.11-4.26) 3.08 (2.95-3.21) 3.50 (3.385-3.59) <0.0001 how many patients were seen in your primary practice location? (mean; 95%ci) 149.74 (139.59-159.89) 63.50 (57.81-69.19) 28.24 (23.74-32.73) <0.0001 how many biopsies did you perform for suspicious pigmented skin lesions? (mean; 95%ci) 19.86 (18.02-21.70) 7.75 (6.73-8.78) 3.55 (2.74-4.36) <0.0001 did you selectively postpone non-essential appointments? (%yes; 95%ci) 35.42% (31.89% 38.95%) 79.4% (76.01% 82.51%) 95.6% (94.27% 96.88%) <0.0001 how many biopsies were postponed? (mean; 95%ci) 3.89 (3.06-4.73) 10.75 (9.19-12.31) 7.84 (6.62-9.05) <0.0001 prospective estimates march 16-20 april 13-18 relative to your practice during the week of march 16-20 (survey 2: april 13-18; survey 3: may 18-23), what do you anticipate your schedule for march 23-april 10 (survey 2: april 20-may 10) will look like? (%; 95%ci) similar schedule & patient load 6.1% 38.5% 0-25% reduction 8.3% 5.6% 26-50% reduction 19.4% 8.7% 51-75% reduction 13.3% 12.5% > 75% reduction (but still open) 34.1% 24.0% completely closing practice 18.9% 10.7% what percentage of appointments did you do using telemedicine (0-100%)? (%; 95%ci) 0% 20.1% 10% 14.8% 20% 7.0% 30% 4.2% 40% 2.5% 50% 5.0% 60% 2.9% 70% 4.4% 80% 7.0% 90% 16.1% 100% 16.0% overall (mean) 48.6% in the next month, what percentage of your patient visits will be done using telemedicine because of covd-19? (mean; 95%ci) 37.8% 45.9% skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 32 figure 1. covid-19 hotspots as of april 18, 2020. section codes geographic description section codes geographic description section codes geographic description section codes geographic description 018 boston metro area 330 miami metro area 780* san antonio, tx 919* san diego metro area 019 331 782 920 021 333 786 austin, tx 921 024 334 787 922 070-071 new york metro area 480 detroit metro area 800 denver metro area 923 073* 481 801 925 076 483 802 926 los angeles metro area 085*-086 600 chicago metro area 804 928 100-101* 601 816* eagle county, co 940 san francisco bay area 103 602 900 los angeles metro area 941 104 604 901* 950 105 605 902 951 108* 606 904 956 sacramento, ca 109 700* new orleans, la 905 957 110 701 906* 958 112 750 dallas metro area 907 980 seattle metro area 113 752 908 981 115 765* waco, tx 910 983 117,119 766* 913 302 atlanta, ga 770 houston metro area 914* 303 774-775* 915 *survey 1 only. note: 36% (survey 1) and 34% (survey 2) of dermatologists (survey respondents) practiced in these high-density (“hotspot”) disease areas skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 33 a greater negative impact was found in us “hotspot” regions4 (36% (survey 1) and 34% (survey 2) of respondents-figure 1) for week 3/16-20 for practice days (3.0 hotspots vs. 3.3 non-hotspots) and patients seen (56.2 in hotspots vs. 70.0 in non-hotspots); and for week 4/13-18 (3.4 in hotspots vs 3.5 in non-hotspots) and patients seen (25.3 in hotspots vs 29.7 in non-hotspots). no significant differing telemedicine usage (39.5% hotspots vs 37.2% non-hotspots) or practice closure (21.0% hotspots vs 17.6% non-hotspots) was found in survey 1 (march); however, a significant difference in telemedicine usage (54.5% hotspots vs 45.5% non-hotspots) and practice closure (25.4% hotspots vs 16.4% non-hotspots, when compared to a typical april week) was found in survey 2 (april). mean estimated telemedicine visits overall for the next 2 weeks was 37.8% (survey 1) and 45.9% (survey 2). academic/university/institutional dermatologists were significantly more likely to use telemedicine (survey 1=57.1%, survey 2=68.6%) than private practitioners (survey 1=35.5%, survey 2=46.2%). telemedicine usage was less likely for dermatologists with >30 practice years (>30=32.4% vs 40.0%) and this trend continued in april with only 37.2% of more experienced dermatologists using telemedicine. however, telemedicine usage does not have an impact on the deferred/postponed biopsies that had already occurred during the march (mean=10.7) or april (mean=7.9) weeks as well as those predicted to be subsequently postponed. limitations include that this study reflects a “snapshot” which could materially change given the dynamically evolving situation. estimations could have led to recall bias and the 10.1% response rate could have introduced sampling and non-response bias. those with lower work volumes could have been more likely to have time to respond, but this bias was minimized by weekend-only data collection. however, the large sample size and representative distribution mitigate selection bias and standard statistical testing demonstrated significance. our findings demonstrate the significant early impact of covid-19 on us dermatologic care and can help better understand national trends. with an estimated 49.9 million annual us dermatology office visits5, the 50%+ decrease in predicted visits could be devastating. beyond telemedicine, other innovative approaches will need to be developed and implemented to help delivery of essential dermatology care during this crisis. conflict of interest disclosures: none funding: none corresponding author: graham h litchman, do, ms department of dermatology st. john’s episcopal hospital far rockaway, ny 11691 email: graham.litchman@gmail.com references: 1. r emanuel ej, persad g, upshur r, et al. fair allocation of scarce medical resources in the time of covid-19. new england journal of medicine. 2020. doi:10.1056/nejmsb2005114. 2. chen y, pradhan s, xue s. what are we doing in the dermatology outpatient department amidst the raging of the 2019 novel coronavirus? journal of the american academy of dermatology. 2020;82(4):1034. doi:10.1016/j.jaad.2020.02.030. 3. cases of coronavirus disease 2019 (covid-19) in the u.s. by centers for disease control and prevention website. https://www.cdc.gov/coronavirus/2019ncov/cases-updates/cases-inus.html?cdc_aa_refval=https%3a%2f%2fwww.cdc. gov%2fcoronavirus%2f2019-ncov%2fcases-inus.html#anchor_1586790730. accessed april 23, 2020. 4. coronavirus covid-19 global cases by the center for systems science and engineering at johns hopkins university website. https://gisanddata.maps.arcgis.com/apps/opsdashboar d/index.html#/bda7594740fd40299423467b48e9ecf6. updated march 24, 2020. accessed march, 24, 2020. 5. rui p, okeyode t. national ambulatory medical care survey: 2016 national summary tables. available from: https://www.cdc.gov/nchs/data/ahcd/namcs_summary/ 2016_namcs_web_tables.pdf discussion conclusion https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/cases-in-us.html?cdc_aa_refval=https%3a%2f%2fwww.cdc.gov%2fcoronavirus%2f2019-ncov%2fcases-in-us.html#anchor_1586790730 https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/cases-in-us.html?cdc_aa_refval=https%3a%2f%2fwww.cdc.gov%2fcoronavirus%2f2019-ncov%2fcases-in-us.html#anchor_1586790730 https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/cases-in-us.html?cdc_aa_refval=https%3a%2f%2fwww.cdc.gov%2fcoronavirus%2f2019-ncov%2fcases-in-us.html#anchor_1586790730 https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/cases-in-us.html?cdc_aa_refval=https%3a%2f%2fwww.cdc.gov%2fcoronavirus%2f2019-ncov%2fcases-in-us.html#anchor_1586790730 https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/cases-in-us.html?cdc_aa_refval=https%3a%2f%2fwww.cdc.gov%2fcoronavirus%2f2019-ncov%2fcases-in-us.html#anchor_1586790730 https://gisanddata.maps.arcgis.com/apps/opsdashboard/index.html#/bda7594740fd40299423467b48e9ecf6 https://gisanddata.maps.arcgis.com/apps/opsdashboard/index.html#/bda7594740fd40299423467b48e9ecf6 https://gisanddata.maps.arcgis.com/apps/opsdashboard/index.html#/bda7594740fd40299423467b48e9ecf6 skin january 2019 volume 3 issue 1 copyright 2018 the national society for cutaneous medicine 44 short communications a case of azacitidine-induced toxic erythema of chemotherapy catherine linsley, bs1, mina aziz, ba1 1department of dermatology, icahn school of medicine at mount sinai, new york, ny myelodysplastic syndromes (mds) are a heterogeneous group of disorders, recognized in a clinical setting by a decrease in bone marrow function and characterized by chronic cytopenias with approximately one-third of patients progressing to acute myeloid leukemia (aml).1 in recent years, the chemotherapy agent azacitidine has been shown to be an effective treatment for mds, increasing overall survival and lowering the rate of progression to aml.2 azacitidine is a dna hypomethylating agent that acts by inhibiting dna methyltransferase, thereby reactivating normal hematopoiesis.3 the most common adverse reactions include: injection site reactions, gastrointestinal issues, and cytopenias.4 adverse events are expected with treatment initiation, but they have been found to improve over time. current evidence recommends continuing therapeutic dosages of azacitidine despite side effects, as most side effects can be managed throughout the course of treatment.4 adverse events may be managed with dosing delays/reductions, blood transfusions, and antibiotics for severe cytopenias, anti-emetics, laxatives and antidiarrheals for gastrointestinal issues, and topical corticosteroids and/or anti-histamines for injection site reactions. toxic erythema of chemotherapy (tec) is a well-described spectrum of overlapping toxic reactions to chemotherapy, most often associated with use of cytarabine, anthracyclines, 5‐fluorouracil, capecitabine, taxanes, and methotrexate.5 tec is clinically characterized by painful erythematous, violaceous, and/or edematous plaques of the hands, feet, and intertriginous regions that may have a dusky appearance and develop bullae with subsequent erosions.5 however, tec following azacitidine therapy has not been reported. here we present a rare case of azacitidine-induced tec. an 83-year-old female presented to our practice with diffuse, scaly, erythematous papules coalescing into plaques throughout her body, sparing the face, scalp, and genitals (figure 1). the lesions were severely pruritic and had been present for 2 months, with prominent involvement of her arms, trunk, and back. her past medical history was significant for mds for 3 years, controlled on monthly azacitidine, until transformation to aml due to missing 2 cycles of treatment. introduction case report skin january 2019 volume 3 issue 1 copyright 2018 the national society for cutaneous medicine 45 figure 1: scaly erythematous plaques on right arm (biopsied). the patient was seen by another dermatologist 2 weeks after the rash appeared. the lesion was biopsied, showing perivascular and granulomatous dermatitis, consistent with a drug reaction. the patient was given triamcinolone acetonide injections with daily mupirocin for open lesions and referred to our clinic. upon examination and biopsy review, the patient was diagnosed with tec due to azacytidine. she was prescribed clobetasol spray twice daily for 24 weeks. the patient was continued on azacitidine, without change to the treatment regimen, and the lesions began to diminish following the appropriate topical therapy. many conditions fall within the spectrum of tec, including erythrodysesthesia, acral erythema, hand‐foot syndrome, toxic erythema of the palms and soles, eccrine squamous syringometaplasia, epidermal dysmaturation, and neutrophilic eccrine hidradenitis (neh).5 while azacytidineassociated tec has not previously been reported, there was a single report of decitabine-associated neh.6 both chemotherapies are cytidine analogs acting as hypomethylating agents, and both have been approved for the treatment of mds and aml. tec is usually self‐limited and resolves after desquamation and post-inflammatory hyperpigmentation.5 therapeutic options are nonspecific and primarily palliative in nature (cool compresses, analgesics, bland emollients, topical corticosteroids, and topical antibiotics or ointments for erosions).5 the role of hypomethylating agents in mds and other hematological conditions is significant, thus clinicians should remain aware of this complication and its possible therapeutic implications. conflict of interest disclosures: none. funding: none. corresponding author: mina aziz icahn school of medicine at mount sinai new york, ny mina.aziz@icahn.mssm.edu references: 1. raj k, mufti gj. azacytidine (vidaza®) in the treatment of myelodysplastic syndromes. ther clin risk manag. 2006;2(4):377-388. 2. fenaux p, mufti gj, hellstrom-lindberg e, et al. efficacy of azacitidine compared with discussion mailto:mina.aziz@icahn.mssm.edu skin january 2019 volume 3 issue 1 copyright 2018 the national society for cutaneous medicine 46 that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomized, open-label, phase iii study. lancet oncol. 2009;10(3):223-32. 3. silverman lr. dna methyltransferase inhibitors in myelodysplastic syndrome. best pract res clin haematol. 2004;17(4):585-94. 4. almeida am, pierdomenico f. generalized skin reactions in patients with mds and cmml treated with azacitidine: effective management with concomitant prednisolone. leuk res. 2012;36(9):e2113. 5. bolognia jl, cooper dl, glusac ej. toxic erythema of chemotherapy:a useful clinical term. j am acad dermatol. 2008;59(3):5249. 6. ng es, aw dc, tan kb, et al. neutrophilic eccrine hidradenitis associated with decitabine. leuk res. 2010;34(5):e130-2. powerpoint presentation skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 771 original research clinicianand patient-reported outcomes with tirbanibulin 1% treatment for actinic keratosis in routine clinical practice across the u.s. (proak study) todd schlesinger, md,1 leon kircik, md,2,3 james del rosso, do,4,5,6 darrell rigel, md, ms,2 mark lebwohl, md,2 brian berman, md, phd,7 april armstrong, md,8 neal bhatia, md,9 vishal a. patel, md,10 siva narayanan, phd,11 volker koscielny, md,12 ismail kasujee, phd12 1 clinical research center of the carolinas, charleston, sc 2 icahn school of medicine at mount sinai, new york, ny 3 skin sciences, pllc, louisville, ky 4 jdr dermatology research/thomas dermatology, las vegas, nv 5 touro university nevada, henderson, nv 6 advanced dermatology and cosmetic surgery, maitland, fl 7 university of miami miller school of medicine, miami, fl 8 keck school of medicine, university of southern california, los angeles, ca 9 therapeutics clinical research, san diego, ca, usa 10 george washington school of medicine and health sciences, washington, dc 11 avant health llc, bethesda, md 12 almirall sa, barcelona, spain abstract background: patients' experiences regarding topical actinic keratosis (ak) treatments may optimize clinical outcomes. proak study aimed to evaluate patientand clinician-reported outcomes among adult patients with ak on face or scalp who were prescribed tirbanibulin in real-world clinical practice in the united states. methods: key primary endpoint was quality of life (qol) assessed by skindex-16. additional endpoints were tirbanibulin treatment effectiveness and satisfaction (treatment satisfaction questionnaire for medication and expert panel questionnaire). results: 290 patients were included in this analysis. at week 8, skindex-16 scores improved in all domains (mean change from baseline [standard deviation, sd]: -14.3 [27.8] in symptoms, -24.9 [33.0] in emotions, and -9.8 [23.7] in functioning domain). clinicians and patients reported high global satisfaction with tirbanibulin (mean [sd] scores of 78.8 [20.1] and of 74.5 [23.5]). overall skin appearance improved from baseline to week 8 (91.0% clinicians; 84.1% patients). in comparison with previous treatments, tirbanibulin had shorter skin reactions duration (89.2% clinicians; 73.9% patients); milder skin reaction severity (91.0% clinicians; 76.6% patients); better daily activities impact (87.4% clinicians; 64.0% patients); and was easier to use (88.3% clinicians; 71.2% patients). investigator’s global assessment (iga) success (0-1) was achieved by 73.8% of the patients. skin photodamage severity reduction from baseline to week 8 was significant (77.4% vs. 39.6%; p<0.0001). conclusions: tirbanibulin treatment demonstrated effectiveness in ak management. moreover, tirbanibulin improved qol, as early as week 8, and both clinicians and patients reported tirbanibulin treatment convenience, and high levels of treatment satisfaction, compared to patient’s previous treatments. skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 772 actinic keratoses (aks) are dysplastic keratinocyte lesions caused by cumulative sun-exposure and ultraviolet radiation and are associated with fair skin and increasing age.1–15 aks are common skin lesions that affect around 58 million people in the united states (u.s.) and are one of the most frequent skin diagnoses.2,4,8,14 these cutaneous lesions are rough erythematous papules, particularly on face, scalp, and extremities, with potential to progress to squamous cell carcinoma.1–3,6,7 all forms of ak must be treated and it is important to assess how to manage ak most effectively, owing to high prevalence of ak and the inability to predict which lesions will become cancerous.2,12,16 currently, there are two major categories of ak treatments: lesion-directed (cryosurgery and excisional therapies) and field-directed therapies (topical therapies, and photodynamic therapy [pdt]).7,10–12,15 tirbanibulin is a novel synthetic chemical drug with potent antitumor and antiproliferative activity, with a simple dosage regimen that favors adherence.2,10 it was approved by the u.s. food and drug administration for treatment of aks on december 14, 2020.2 phase ii and iii clinical trials have shown tirbanibulin to be efficacious with a favorable tolerability and safety profile on face and scalp after a short course of daily treatment for 5 consecutive days.3,17 in phase iii clinical trials, patients treated with tirbanibulin experienced higher complete (100%) clearance (cc) levels (44% in trial 1; 54% in trial 2) than those treated with control ointment (5% trial 1; 13% trial 2; p<0.001 for both trials) at day 57.3 most common local skin reactions (lsr) were transient erythema (91% of patients) and flaking or scaling (82% of patients).3 however, these reported outcomes may not fully capture the patient experience with the treatment. although clinical studies of topical treatments result in high therapeutic efficacy, in realworld, treatment length, regimen complexity, lsr presence and recurrence rates may impact treatment adherence, leading to poor outcomes.2,6,14,18 in addition, ak lesions occur primarily on visible, sun-exposed areas, and negatively affect patients’ quality of life (qol), affecting emotional and social functioning.19,20 therefore, it is critical to understand patients' experiences and preferences regarding ak treatments, as their perspective may optimize adherence and clinical outcomes.7,19 achievement of long-term treatment outcomes depends on patient’s and clinician’s treatment risk-benefit perceptions.15,18 moreover, patient satisfaction with treatment and qol can affect treatment-related behaviors, such as correct and continuous use of medication.21 hence, patient-reported outcomes (pro) are important measures concerning health status and medication experience coming directly from the patient.13 pro instruments could be categorized into ak-specific and non-specific instruments7 and the most commonly used are skindex and treatment satisfaction questionnaire for medication (tsqm) surveys.15 the need of an ak-specific pro instrument brought together a nine-person expert panel of dermatologists to develop the first ak-specific measure (expert panel questionnaire [epq]) of pros and clinicianreported outcomes (clinros) for comparative use.16 comparing patient and clinician perspectives may help optimize precision in ak treatment. ak-epq was first introduction skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 773 implemented in this study19 and will be used in future research studies of ak treatments. here, we present the interim results of proak (patient-reported outcomes in actinic keratosis) study that evaluated pros and clinros among adult patients with aks on face or scalp who were prescribed tirbanibulin in real-world clinical practice in the u.s. study population and design proak is an observational, single-arm, prospective, multicenter, phase iv study (nct05260073) among adult patients with ak on face or scalp who have initiated treatment with tirbanibulin (as per label) in real-world clinical practices in the u.s., as part of routine care.19 patients were followed for 6 months post-treatment initiation. adults aged ≥18 years at time of treatment initiation with tirbanibulin, diagnosed with ak on face or scalp with clinically typical, visible, and discrete ak lesions, were included in the proak study. patients with any dermatological condition of face or scalp that could interfere with clinical evaluations and patients with hypertrophic ak lesions, open wounds, or suspected skin cancers too close to treatment area were excluded from the study. patients and clinicians completed surveys and clinical assessments concerning safety and effectiveness of tirbanibulin at baseline, week 8 (timeframe for main endpoints) and week 24. surveys results and clinical assessments at week 8 are presented here. the study was performed at 32 private dermatology practices across the u.s. in accordance with ethical principles that had their origin in the declaration of helsinki and were consistent with the international council for harmonization. the study was reviewed by an independent ethics committee. all patients signed the informed consent form. outcomes primary endpoint was patient-reported qol assessed by skindex-16 at week 8.22,23 skindex-16 consists of 16 items classified into three domains: symptoms (four items: itching, burning, hurting, irritation), emotional impact (seven items: bothered about persistence/recurrence, appearance, worry about condition, frustration, embarrassment, being annoyed, feeling depressed) and functioning (five items: impact on interactions with others, desire to be with people, showing affection, daily activities, work, or other activities). total score is the average of all items and transformed to a linear scale of 100 varying from 0 (never bothered) to 100 (always bothered). the higher the score, the more severe the impairment. additional endpoints included patient and clinician satisfaction with tirbanibulin treatment, assessed by tsqm-921 and epq16 at week 8, treatment effectiveness assessed by investigator’s global assessment (iga) and clinician rating of severity of skin photodamage at week 8 and week 24, safety, and tolerability (last two additional endpoints are not presented here). tsqm-9 measured patient satisfaction with treatment on three key domains: effectiveness, convenience, and global satisfaction. most items (from item 1 to 6 and item 9) are scored on a seven-point likert scale from 1 (extremely dissatisfied/difficult/inconvenient) to 7 (extremely satisfied/easy/convenient). items 7 and 8 of tsqm-9 are scored on a five-point scale from 1 (not at all confident/certain) to 5 (extremely confident/certain). tsqm-9 methods skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 774 subscale scores are transformed to scores ranging from 0 to 100, with higher scores representing higher satisfaction on respective domains. an adapted version of tsqm-9 (same domains and scoring) was given to clinicians to measure their satisfaction with tirbanibulin treatment. regarding the epq, eleven questions were designed to measure patient and clinician’s perspectives of clinical and cosmetic outcomes associated with ak, effect of treatment related lsr, and overall relative satisfaction with treatment. items 1 to 9 were designed to be answered by both patient and clinician, whereas items 10 and 11 assess skin clearance (iga of ak status) and photodamage, were designed to be answered by only clinicians. clinician version of epq refers to clinician experience and observation of treatment effects among their patients. overall skin appearance was rated on a fivepoint adjectival response scale of 0 (much worse) to 4 (much improved) and satisfaction with ‘how skin looks’ and ‘skin texture’, on a seven-point response scale of 1 (extremely dissatisfied) to 7 (extremely satisfied) (epq 1-3). lsrs duration and severity, impact on daily activities, convenience and ease of use and overall satisfaction compared to previous ak treatments (epq 4-8) were rated on a five-point response scale from 0 (much shorter/better) to 5 (much longer/worse). likelihood to reconsider treatment in future was rated on a five-point scale of 0 (very unlikely) to 5 (very likely) (epq 9). ak responses were assessed using iga on a five-point response scale of 0 (completely cleared) to 4 (not cleared) (epq 10). iga success was defined as achieving an iga score of 0-1 (≥75% ak lesions clearance) at week 8. clinicians assessed patient’s skin photodamage severity on a four-point response scale of 0 (absent) to 3 (severe) (epq 11). lsrs were graded by clinicians, and, in one site, photographs were captured to assess lsrs progression. statistical analysis timepoint was week 8. validated instruments (skindex-16 and tsqm-9) were scored according to developer guidelines, reporting domain scored and overall summary scores. for all study variables and endpoints, no missing data imputation was planned. data were presented descriptively using summary statistics, including percentage for categorical data, and mean with standard deviation (sd) and minimum and maximum for continuous data. change from baseline (cfb) in skindex-16 score was explored using relevant multivariate analyses. pearson correlation coefficients were used to assess the correlation between key outcome measurements. all analyses were performed using sas version 9.4 (sas institute, cary, nc, usa). patient characteristics a total of 300 patients were enrolled in the study. ten of the enrolled patients were not included in the week 8 analyses due to missing data (one patient), or patient voluntary withdrawal of consent or lost to follow-up (nine patients). therefore, a total of 290 patients with data from week 8 assessments were included in the interim analysis. most of patients were male (68.6%) and the mean age (sd) was 66.3 (11.4) years. overall, 77.9% of patients were diagnosed with ak on the face and 61.7% had a history of skin cancer. 71.4% of results skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 775 table 1. baseline patient characteristics. patients (n=290*) age, mean (sd) [min, max], years 66.3 (11.4) [30.0, 90.0] gender, n (%) female male 91 (31.4) 199 (68.6) ak location (not mutually exclusive), n (%) face scalp 226 (77.9) 98 (33.8) primary health insurance, n (%) private insurance medicaid medicare uninsured 121 (41.7) 9 (3.1) 156 (53.8) 4 (1.4) history of skin cancer, n (%) 179 (61.7) fitzpatrick skin type, n (%) type i type ii type iii type iv type v 22 (7.6) 207 (71.4) 54 (18.6) 4 (1.4) 3 (1.0) baseline patient self-reported skin-texture, n (%) dry smooth rough bumpy scaly blistering peeling 115 (39.7) 138 (47.6) 57 (19.7) 54 (18.6) 102 (35.2) 1 (0.3) 18 (6.2) ak, actinic keratoses; sd, standard deviation. *ten patients were not included in the week 8 analyses: 1 patient had missing data, and 9 patients were discontinued from the study due to patient voluntary withdrawal of consent or lost to follow-up. skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 776 patients had fitzpatrick skin type ii and 47.6% of patients self-reported to have a smooth skin-texture. patient characteristics are depicted in table 1. all patients completed their tirbanibulin treatment course (once daily for 5 days) and more than 75% of patients were treated with tirbanibulin between april and august 2022. qol assessed by skindex-16 mean (sd) scores decreased from baseline to week 8 in all three domains: symptoms (22.3 [22.4] to 8.0 [13.8]), emotions (38.2 [27.3] to 13.3 [20.1] and functioning domains (14.4 [20.1] to 4.6 [12.0] (figure 1). the mean (sd) skindex-16 cfb in symptoms, emotions and functioning domains were 14.3 (27.8), -24.9 (33.0) and -9.8 (23.7), respectively. decrease in scores from baseline to week 8 was statistically significant (p<0.0001) for all skindex-16 domains. treatment satisfaction assessed by tsqm-9 and epq regarding tsqm-9 responses, clinician and patient satisfaction with tirbanibulin was high at week 8. both clinicians and patients reported the highest satisfaction in the convenience of use subscale (mean [sd] scores of 85.3 [14.9] and 85.8 [14.3], respectively) followed by global satisfaction (mean [sd] scores of 78.8 [20.1] and 74.5 [23.5], respectively) and effectiveness (mean [sd] scores of 76.4 [21.5] and 73.0 [21.7], respectively) (figure 2). regarding epq responses, 91.0% of clinicians and 84.1% of patients considered that overall skin appearance much or somewhat improved from baseline to week 8 using tirbanibulin (figure 3a). moreover, 79.0% of clinicians and 75.9% of patients were extremely or very satisfied with the improvement in how skin looked (figure 3b) and 80.7% of clinicians and 74.8% of patients were extremely or very satisfied with skin texture improvement (figure 3c). a total of 111 out of 290 patients (38.3%) had used a topical medication in the past, with 5fluorouracil (5-fu) being the most frequent (66.7%), followed by imiquimod (28.8%), ingenol mebutate (11.7%) and diclofenac (7.2%). duration of skin reactions was considered much or somewhat shorter with tirbanibulin in comparison with previous topical ak medications by 89.2% of clinicians and 73.9% of patients (figure 4a); 91.0% of clinicians and 76.6% of patients considered that the severity of skin reaction was much or somewhat better with tirbanibulin (figure 4b); 87.4% of clinicians and 64.0% of patients considered that the impact on daily activities due to skin reactions associated with tirbanibulin use was much or somewhat better than with previous topical medications (figure 4c); and 88.3% of clinicians and 71.2% of patients considered that tirbanibulin treatment was much or somewhat easier to use in comparison with other previous topical medications (figure 4d). overall satisfaction with tirbanibulin compared with previous ak treatments was rated as much or somewhat better by 82.9% of clinicians and 72.1% of patients (figure 4e). likewise, 85.2% of clinicians and 80.0% of patients reported their desire to consider tirbanibulin again, if needed, to treat ak lesions. on the other hand, the proportion of patients with completely/partially cleared ak (iga 01) was 73.8% (iga success) at week 8. among 288 patients with available data at both baseline and week 8, 77.4% of patients had moderate/severe skin photodamage at baseline and 39.6% of patients at week 8. reduction of skin photodamage severity at week 8 was statistically significant (p<0.0001). skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 777 figure 1. evaluation of patient-reported ak symptoms, impact on emotions and functioning. skindex16 qol one & four patients had missing data at baseline for symptom & emotions domain respectively; one patient had missing data at week-8 for emotions domain. over the past week… sk1: how often have you been bothered by itching? sk2: how often have you been bothered by burning or stinging? sk3: how often have you been bothered by your skin condition hurting? sk4: how often have you been bothered by your skin condition being irritated? sk5: how often have you been bothered by persistence/recurrence of skin condition? sk6: how often have you worried about your skin condition spreading, worsening, scarring (etc.) skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 778 sk7: how often have you been bothered by the appearance of your skin condition? sk8: how often have you been frustrated by your skin? sk9: how often have you been embarrassed by your skin? sk10: how often have you been annoyed about your skin? sk11: how often have you been feeling depressed about your skin condition? sk12: how often has your interactions with others been affected by your skin condition? sk13: how often has your interactions with others been affected by your skin condition? sk14: how often has skin condition made it hard to show affection? sk15: how often has your skin affected your daily activities? sk16: how often has skin condition made it hard to work or do what you enjoy? ak, actinic keratoses; cfb, change from baseline to week-8; qol, quality of life. *p<0.0001 skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 779 figure 2. clinicians’ and patients’ reported satisfaction with tirbanibulin treatment. tsqm-9. tsqm, treatment satisfaction questionnaire for medication. *adapted from patient-version of tsqm-9. skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 780 figure 3. clinicians and patients rating of overall appearance of the skin. epq. epq, expert panel questionnaire. skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 781 figure 4. clinicians and patients’ outcomes regarding tirbanibulin in comparison with other previous topical medications. epq. epq, expert panel questionnaire. skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 782 figure 5. clinical clearance at days baseline, week 1, week 2, week 4 and week 8 with use of tirbanibulin for actinic keratoses on face. skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 783 photographs photographs were taken of ten patients. two patients were selected for demonstration. photographs were taken at baseline, week 1, week 2, week 4 and week 8 (figure 5). patient 1 was a 78-year-old male treated with tirbanibulin for aks on face. the patient had previously been treated for ak with cryosurgery and 5-fu/calcipotriene. patient 2 was a 69-year-old male treated for aks on the face. the patient had previously been treated for aks with cryosurgery, blu-u pdt, and efudex 5% cream. in both patients, cc (100%) levels were achieved before week 8. in the real-world setting, adherence to therapy is important to achieve optimal outcomes. however, adherence can be compromised by patients’ perception and satisfaction with the treatment. hence, pros, not always included in clinical trials, may inform clinicians about patients’ preferences and what patients value the most for the ak treatment. proak study provides the opportunity to evaluate both pros and clinros among adult patients with aks on face or scalp treated with tirbanibulin in realworld clinical practice in the u.s. the skindex-16 survey was used in the proak study to comprehensively assess the impact of tirbanibulin on health-related qol. under real-world circumstances, tirbanibulin treatment improved qol of patients, as early as in week 8, as indicated by the significant reduction of ak burden regarding symptoms, emotions, and functional impact from baseline. in this study, cfb reflects a large improvement in all the skindex-16 domains (14.3 in symptoms domain, -24.9 in emotions domain, and -9.8 in functioning domain). on the contrary, studies assessing healthrelated qol, using skindex-17 or skindex29, showed generally low impairment in patients with ak before the start of the therapy and reflected small improvements in qol after treatment with other topical ak treatments (5-fu, imiquimod, methyl aminolevulinate, ingenol mebutate).13,24,25 regarding satisfaction with treatment at week 8, assessed by tsqm-9 survey, both clinicians and patients agreed in the effectiveness and convenience of tirbanibulin treatment, reporting high levels of global satisfaction (79 and 75 mean score in clinicians and patients, respectively), higher than those reported in other studies using ak topical treatments. in the rapid-act study9, in denmark and sweden, patients diagnosed with ak and treated with diclofenac gel, imiquimod (3.75% or 5%) or ingenol mebutate (150 lg/g or 500 lg/g) reported, at week 3, a higher global satisfaction with imiquimod (64 tsqm-9 mean score) compared with diclofenac (61 tsqm-9 mean score) and ingenol mebutate (60 tsqm-9 mean score). on the other hand, in a phase iii, multicenter, randomized study12 in germany and uk, overall treatment satisfaction was greater among patients with ak that received 5-fu than in patients that received vehicle (69 vs. 56 tsqm-1.4 mean score). to our knowledge, this is the first study assessing satisfaction with ak treatment using tsqm-9 in the u.s. furthermore, this is the first study using the new ak-epq survey16. ak-epq was designed to capture both clinro and pro regarding ak treatment considering clinical and cosmetic outcomes associated with ak, effect of treatment related lsr, and overall satisfaction. comparing both perspectives may help optimize ak treatment and enhance clinician-patient communication. moreover, comparison of current and discussion skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 784 previous ak treatments could be useful to measure the relative impact of different treatments. therefore, the fact that both clinicians and patients better rated the attributes of tirbanibulin compared to previous treatments (shorter duration, ease of use, less lsr severity, better impact on patient's daily activities) and reported their desire to consider tirbanibulin again, highlights the benefits of this novel therapeutic option for the optimal management of aks. clinician-reported satisfaction with tirbanibulin treatment compared with previous ak topical medications was higher than patient-reported satisfaction, most likely due to clinicians comparing the results based on their daily experience with ak patients. in addition, most patients and clinicians reported improvement in overall skin appearance in tirbanibulin-treated area at week 8. moreover, clinicians reported a significant reduction in severity of skin photodamage from baseline to week 8 (77% vs. 40%; p<0.001) and most patients (74%) experienced iga success (75-100% clearance). in conditions close to real clinical practice, tirbanibulin demonstrated effectiveness in aks treatment, similar to that obtained in phase iii clinical trials of patients with ak receiving tirbanibulin or control ointment3. in phase iii clinical trials, at day 57, 44% and 54% of patients in the tirbanibulin group of trials 1 and 2, respectively, achieved cc (100%) of all ak lesions; whereas 68% and 76% of patients in the tirbanibulin group of trials 1 and 2, respectively, achieved partial (≥75%) clearance of ak lesions.3 results may be subjected to bias such as recall bias, reporting bias, selection bias, and other biases commonly seen in real-world studies and open-label studies. approaches such as standardized study inclusion/exclusion criteria, consecutive sampling, and geographically diverse dermatology clinics, with varied experience with oral antibiotics were employed to minimize these biases. by contrast, this study has some strengths as to be able to assess qol, treatment satisfaction and short-term effectiveness in daily practice tirbanibulin use in ak patients. moreover, the newly developed ak-specific pro and clinro instrument (epq16) obtains information about patient and clinician experience with ak treatments and comparing both perspectives can help to improve precision of ak treatments. in real-world routine community practice, tirbanibulin treatment demonstrated effectiveness, as evidenced in phase iii clinical trials3, highlighting the clinical and humanistic benefits associated with this novel therapeutic option for optimal management of aks. moreover, tirbanibulin improved qol among patients with ak, as early as in week 8, and both clinicians and patients agreed in the convenience of tirbanibulin treatment, reporting high levels of treatment satisfaction and likelihood to consider its use again, if needed. compared to patient’s previous treatment, clinicians found a shorter duration and milder severity of skin reactions associated with tirbanibulin use, and a better impact in the daily activities of their patients, citing tirbanibulin as highly convenient. tirbanibulin was better rated when compared to previous topical treatments in all questions. finally, assessing both clinro and pro among patients with ak in real-world setting is important to improve our understanding of patient burden and to inform healthcare professionals and conclusion skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 785 payers to aid their clinical and reimbursement decisions, respectively. acknowledgements: the authors would like to thank alina gavrus ion, phd, and irene mansilla núñez, msc, from tfs healthscience for editorial assistance and writing support. conflict of interest disclosures: ts: consulting honoraria from abbvie, allergan, almirall, arcutis, biofrontera, bms, castle bioscience, cms aesthetics dcme, epi health, foundation for research and education in dermatology, galderma, genentech, kintor, lilly, merz, nextphase, novartis, ortho dermatologics, pfizer, pharmatecture, pierre fabre, plasmed, prolacta bioscience, pulse biosciences, regeneron, skinceuticals/l’oreal, sun pharma, ucb, and verrica. grant/research funding from abbvie, aclaris, allergan, amgen, almirall, anterios, ao biome, arcutis premier research, aslan, astellas pharma us, athenex, biofrontera, biorasi, boehringer ingelheim, brickell biotech, bms, cara therapeutics, castle bioscience, celgene, chemocentryx, coherus bioscience, concert pharmaceutical, corrona, cutanea life sciences, dermavant, dermira, epi health, galderma, highlitll, incyte, janssen, leo, lilly, merz, nimbus, novartis, pfizer, processa, pulse biosciences, regeneron, sanofi genzyme, sisaf, trevi, and verrica. speakers’ bureau/advisory board honoraria from abbvie, almirall, amgen, arcutis, bioderma, bms, biofrontera, celgene, sun pharma, epi health, leo, lilly, pfizer, regeneron, remedly, sanofi genzyme, ucb. owns stock from amgen, bms, lilly, and remedly. lk: has served as an investigator, speaker, advisory board member, or consultant for abbott laboratories, aclaris, inc, allergan, inc, almirall, anacor pharmaceuticals, inc, assos pharma, astellas pharma us, inc, asubio pharma co, ltd, berlex laboratories (bayer healthcare pharmaceuticals), biogen-idec, inc, biolife, biopelle, boehringer ingelheim, breckinridge pharma, celgene corporation, centocor, inc, colbar, collagenex, combinatrix, connetics corporation, coria, dermik laboratories, dermira, inc, dow pharmaceutical sciences, inc, dusa pharmaceuticals, inc, eli lilly & co, embil pharmaceutical co, ltd, eos, ferndale laboratories, inc, galderma laboratories, lp, genentech, inc, glaxosmithkline, plc, health point ltd, idera, inc, innocutis medical, llc, innovail, intendis, inc, johnson & johnson, laboratory skin care, inc, leo pharmaceuticals, inc, l’oreal sa, 3m, maruho co, ltd, medical international technologies, medicis pharmaceutical corp, merck & co, inc, merz, nano bio corporation, novartis pharmaceutical corporation, noven pharmaceuticals, inc, nucryst pharmaceuticals corporation, obagi medical products, inc, onset, ortho dermatologics, orthoneutrogena, pediapharma, inc, promius pharma, llc, pharmaderm, pfizer, inc, puracap, qlt, inc, quatrix, quinnova, serono (merck-serono international sa), skinmedica, inc, stiefel laboratories, inc, sun pharmaceutical industries, ltd, taro, tolerrx, inc, triax, ucb, inc, valeant pharmaceuticals north america llc, warnerchilcott, xenoport, inc, and zage. jdr: researcher, consultant, and speaker for almirall. dr: has served as a consultant for almirall, castle biosciences, dermtech, and scibase. ml: research funds from: abbvie, amgen, arcutis, avotres, boehringer ingelheim, cara therapeutics, dermavant sciences, eli lilly, incyte, janssen research & development, llc, ortho dermatologics, regeneron, and ucb, inc.consultant for aditum bio, almirall, altrubio inc., anaptysbio, arcutis, inc., aristea therapeutics, avotres therapeutics, brickell biotech, boehringeringelheim, bristol-myers squibb, cara therapeutics, castle biosciences, celltrion, corevitas, dermavant sciences, dr. reddy, epi, evommune, inc., facilitatation of international dermatology education, forte biosciences, foundation for research and education in dermatology, galderma, helsinn, incyte, leo pharma, meiji seika pharma, mindera, pfizer, seanergy, strata, trevi, and verrica. bb: consulting honoraria from almirall, biofrontera, bms, pfizer, evommune, aiviva, sirnaomics, pulse, mediwound, bpgbio, lemonex and minolabs. aa served as a research investigator, scientific advisor, and/or speaker to abbvie, almirall, arcutis, aslan, beiersdorf, bi, bms, epi, incyte, leo, ucb, janssen, lilly, mindera, nimbus, novartis, ortho dermatologics, sun, dermavant, dermira, sanofi, regeneron, and pfizer. nb: consulting honoraria from and investigator for almirall, biofrontera, leo, ortho, and sun pharma. vp: speakers bureau for regeneron, advisory board/consultant for regeneron, almirall, phd biosciences, castle biosciences, and shareholder for science 37, avestra. sn: consulting honararia or research funding from almirall, biogen, johnson and johnson, sarepta therapeutics, seagen, and takeda. vk, and ik: almirall employees. funding: this publication was funded by almirall s.a., barcelona, spain. corresponding author: ismail kasujee, phd almirall s.a., general mitre 151 08022 barcelona, spain skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 786 email: ismail.kasujee@almirall.com references: 1. balcere a, rone kupfere m, čēma i, krūmiņa a. prevalence, discontinuation rate, and risk factors for severe local site reactions with topical field treatment options for actinic keratosis of the face and scalp. medicina. 2019;55(4):92. 2. dao dpd, sahni vn, sahni dr, balogh ea, grada a, feldman sr. 1% tirbanibulin ointment for the treatment of actinic keratoses. ann pharmacother. 2022;56(4):494–500. 3. blauvelt a, kempers s, lain e, schlesinger t, tyring s, forman s, et al. phase 3 trials of tirbanibulin ointment for actinic keratosis. n engl j med. 2021;384(6):512–20. 4. criscione vd, weinstock ma, naylor mf, luque c, eide mj, bingham sf, et al. actinic keratoses: natural history and risk of malignant transformation in the veterans affairs topical tretinoin chemoprevention trial. cancer. 2009;115(11):2523–30. 5. del rosso jq, kircik l, goldenberg g, brian b. comprehensive management of actinic keratoses: practical integration of available therapies with a review of a newer treatment approach. j clin aesthet dermatol. 2014;7(9 suppl s2-s12):s2–12. 6. emmerich vk, cull d, kelly ka, feldman sr. patient assessment of 5-fluorouracil and imiquimod for the treatment of actinic keratoses: a retrospective study of real-world effectiveness. journal of dermatological treatment. 2022;33(4):2075–8. 7. grada a, feldman sr, bragazzi nl, damiani g. patient‐reported outcomes of topical therapies in actinic keratosis: a systematic review. dermatologic therapy [internet]. 2021 [cited 2023 mar 2];34(2). available from: https://onlinelibrary.wiley.com/doi/10.1111/dt h.14833 8. grada a, muddasani s, fleischer ab, feldman sr, peck gm. trends in office visits for the five most common skin diseases in the united states. j clin aesthet dermatol. 2022;15(5):e82–6. 9. norrlid h, norlin jm, holmstrup h, malmberg i, sartorius k, thormann h, et al. patientreported outcomes in topical field treatment of actinic keratosis in swedish and danish patients. journal of dermatological treatment. 2018;29(1):68–73. 10. schlesinger t, stockfleth e, grada a, berman b. tirbanibulin for actinic keratosis: insights into the mechanism of action. ccid. 2022;15:2495–506. 11. stockfleth e, peris k, guillen c, cerio r, basset‐seguin n, foley p, et al. a consensus approach to improving patient adherence and persistence with topical treatment for actinic keratosis. int j dermatol. 2015;54(5):509–15. 12. stockfleth e, von kiedrowski r, dominicus r, ryan j, ellery a, falqués m, et al. efficacy and safety of 5-fluorouracil 0.5%/salicylic acid 10% in the field-directed treatment of actinic keratosis: a phase iii, randomized, double-blind, vehicle-controlled trial. dermatol ther (heidelb). 2017;7(1):81–96. 13. waalboer-spuij r, holterhues c, van hattem s, schuttelaar mla, gaastra mtw, kuijpers dim, et al. patient perception of imiquimod treatment for actinic keratosis and superficial basal cell carcinoma in 202 patients. dermatology. 2015;231(1):56–62. 14. kasujee i, diaz gallo c, jose lambert c, massana montejo e, narayanan s. patient perception of disease and treatment burden and new treatment preferences in actinic keratosis. value in health. 2022;25(6, s1). 15. khanna r, bakshi a, amir y, goldenberg g. patient satisfaction and reported outcomes on the management of actinic keratosis. ccid. 2017;10:179–84. 16. bhatia n, armstrong aw, schlesinger t, kircik l, berman b, lebwohl m, et al. an expert panel questionnaire for assessing patient-reported and clinician-reported outcomes in actinic keratosis. j of skin. 2022;6(6):s89. 17. kempers s, dubois j, forman s, poon a, cutler e, wang h, et al. tirbanibulin ointment 1% as a novel treatment for actinic keratosis: phase 1 and 2 results. jdd. 2020;19(11):1093–100. 18. marson j, del rosso j, bhatia n, rigel d. considerations in the management of actinic keratoses: the importance of adherence and persistence to therapy. j of skin. 2021;5(2):83–9. 19. berman b, armstrong a, lebwohl m, grada a, bhatia n, patel v, et al. patient-reported outcomes for tirbanibulin effectiveness and safety in actinic keratosis in real-world settings: proak study protocol. j of skin. 2022;6(2):s19. 20. esmann s, vinding gr, christensen kb, jemec gbe. assessing the influence of skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 787 actinic keratosis on patients’ quality of life: the akqol questionnaire: the akqol questionnaire. british journal of dermatology. 2013;168(2):277–83. 21. bharmal m, payne k, atkinson mj, desrosiers mp, morisky de, gemmen e. validation of an abbreviated treatment satisfaction questionnaire for medication (tsqm-9) among patients on antihypertensive medications. health qual life outcomes. 2009;7(1):36. 22. chren mm, lasek rj, sahay ap, sands lp. measurement properties of skindex-16: a brief quality-of-life measure for patients with skin diseases. j cutan med surg. 2001;5(2):105–10. 23. chren mm, sahay ap, bertenthal ds, sen s, seth landefeld c. quality-of-life outcomes of treatments for cutaneous basal cell carcinoma and squamous cell carcinoma. journal of investigative dermatology. 2007;127(6):1351–7. 24. ahmady s, jansen mhe, nelemans pj, essers bab, kessels jphm, kellenerssmeets nwj, et al. the effect of four approaches to treat actinic keratosis on the health-related qol, as assessed by the skindex-29 and actinic keratosis qol. journal of investigative dermatology. 2021;141(7):1830–2. 25. jubert-esteve e, del pozo-hernando lj, izquierdo-herce n, bauzá-alonso a, martínsantiago a, jones-caballero m. quality of life and side effects in patients with actinic keratosis treated with ingenol mebutate: a pilot study. actas dermo-sifiliográficas. 2015;106(8):644–50. skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 869 original research understanding the factors associated with us dermatology resident trainees’ diagnostic confidence and skill for skin of color pathology alissa jeanfreau, bs1, kaylin beiter, phd1, deborah hilton, md1 1 louisiana state university health sciences center, department of dermatology, new orleans, la inequities in dermatologic health outcomes exist at every level of care delivery including disease prevention, screening, diagnosis, and treatment.1 this translates to worsened clinical outcomes for minority groups. for example, despite a relatively lower incidence of skin cancer overall, black patients with abstract background: inequities in dermatologic health outcomes translate to worsened clinical outcomes for minority groups. for example, despite a lower incidence of skin cancer overall, african americans are diagnosed at later stages with greater degrees of lymph node involvement. this has been shown to lead to disproportionate mortality when compared to lighter skinned individuals. medical education materials contain a significantly lower percentage of skin of color (soc) images than of lighter skin and research has indicated lower diagnostic accuracy of dermatologic conditions in darker skin by u.s. medical students. the objective of this study was to explore u.s. resident dermatologists’ ability to accurately identify skin pathology among soc patients versus lighter skin to potentially identify gaps in training that may contribute to this disproportionate morbidity and mortality. methods: a cross-sectional electronic redcap survey open to all u.s. dermatology residents asked participants their basic demographics (e.g., level of training, racial and ethnic identity) and program characteristics (e.g., geographical location, proportion of patients by fitzpatrick type, presence of a dedicated soc clinic). this data was correlated with participant visual diagnostic accuracy on a 22-item multiple choice quiz (images selected by a senior academic dermatologist) of characteristic nonmalignant and malignant conditions in lighter skin and soc. results: residents preferentially misdiagnosed malignant lesions in soc over lighter skin (p <.0001) and preferentially misdiagnosed malignant lesions in soc over nonmalignant lesions in soc (p <.001). none of the residents’ basic demographic or program characteristic variables had significant relationships with any assessment of performance. conclusion: dermatologists should maintain a high clinical suspicion for malignant conditions in patients with darker skin types, given that these lesions are the most preferentially misdiagnosed and the fact that these lesions carry higher risks for morbidity and mortality. dermatology residency programs should instill efforts to emphasize correct detection of malignant lesions amongst those with skin of color. introduction skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 870 skin cancer are diagnosed at later stages and have a greater degree of lymph node involvement.2 differential (higher) mortality among black patients has been reported as a result.1 the structural causes of these health disparities are multifaceted. identified contributing factors include cultural perception about “immunity” to various dermatologic conditions including skin cancer, socioeconomic barriers to specialty care in general, and the atypical presentation of malignant lesions amongst minority groups.2 one important factor in mitigation of these disparities is accurate diagnosis by a dermatologist. empiric assessments of medical education materials have demonstrated a significantly lower percentage of darker, skin of color images as compared to lighter skin.3 in tandem, medical students’ have lower diagnostic accuracy for dermatologic conditions in darker skin types versus lighter ones.4 while studies have shown that u.s. dermatology residents exposed to more skin of color pathology in their training are more confident in their diagnostic abilities, the impact of such increased exposure on actual diagnostic accuracy has not yet been rigorously assessed.5 the objective of this study was to explore resident dermatologists' ability to identify skin pathology among patients with skin of color in order to examine gaps in training that may exist and subsequently contribute to the disproportionate morbidity and mortality for darker-skinned patients with skin cancer. a cross-sectional redcap-administered survey was distributed to all residency programs in the united states via the association of program directors in dermatology email listserv in august 2022. the survey was open for two months, during which two reminder emails were sent. anonymous participation was requested from all interested dermatology resident physicians in a us-based acgmeaccredited program. participants were asked about their own demographics (including gender, racial and ethnic identity, and training level) as well as basic information about their own program (including geographical location, estimated proportion of patients according to fitzpatrick skin type, and presence of a dedicated skin of color clinic). united states regions were classified as: northeast (maine, vermont, new hampshire, new york, massachusetts, connecticut, rhode island, pennsylvania, new jersey, maryland, and delaware); southeast (arkansas, louisiana, mississippi, alabama, georgia, florida, tennessee, kentucky, west virginia, virginia, north carolina, and south carolina); midwest (north dakota, south dakota, nebraska, kansas, minnesota, iowa, missouri, wisconsin, michigan, illinois, indiana, and ohio); southwest (texas, oklahoma, new mexico, and arizona); and west (washington, oregon, california, idaho, nevada, utah, montana, wyoming, and colorado). all questions were optional. a 22-item multiple choice quiz was also included with images of clinical pathology (non-malignant and malignant) among patients with varying skin colors. a board-certified academic dermatologist with over 20 years of clinical experience evaluated all images for appropriate representation of the given condition and provided a differential diagnosis list (these alternative conditions were used as incorrect answer choices in the quiz). images were then sorted into “light” (predominately caucasian, corresponding to fitzpatrick types i-iii) and “dark” (skin of color patients, fitzpatrick types iv-vi). images of methods skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 871 non-malignant conditions included acne vulgaris, psoriasis, verruca vulgaris, allergic contact dermatitis, atopic dermatitis, herpes zoster, and impetigo. images of malignant lesions included basal cell carcinoma, squamous cell carcinoma in situ, cutaneous squamous cell carcinoma, and melanoma. quiz responses and accuracy were calculated overall as well as sub-scores for accuracy among light vs dark skin tones overall, light malignant lesions vs. dark malignant lesions, and dark non-malignant lesions vs dark malignant lesions. this primary outcome variable, diagnostic accuracy scores (continuous variable), was assessed across respondent demographic variables and program characteristics using sas statistical software version 9.4. prior to dissemination, this study was reviewed and approved by the institutional review board and the association of program directors in dermatology board. explicit permission for image use was sought and granted from the following partner organizations: visualdx, dermnet new zealand, and skindeep. these organizations retain all copyrights to their images. a total of 36 individuals completed the survey. among these approximately half were female (53%, n=18), the majority identified their race as white (71%, n=25) and their ethnicity as not hispanic or latino (89%, n=32). nearly all respondents reported working in an urban setting (97%, n=35). respondents reported coming from a total of 16 different states representing all five regions of the united states. respondents skewed towards earlier in their training, with most being pgy2 level (42%, n=15), followed by pgy3 (33%, n=12), and the least number of respondents being pgy4 (25%, n=9). see table 1. half of respondents reported having no dedicated skin of color clinic (50%, n=18), and three respondents (8.3%) were not sure. there was no statistically significant difference in the proportion of patients with darker skin types (fitzpatrick iv-vi) among respondents with or without a dedicated skin of color clinic (p=0.82). we first assessed overall performance on the assessment tool and found no significant difference between performance across skin types (84.7% correctly diagnosed overall; 85.4% for conditions in light skin types; 84.3% in darker skin types; p>0.05). we then analysed respondent score performance on diagnosis of cancerous conditions for images of patients with lighter versus darker skin types and found a significant difference (100% for conditions in lighter skin types; 75% in darker skin types; p<0.0001). lastly, we assessed score performance when diagnosing malignant versus non-malignant lesions in patients with darker skin types and found that survey respondents performed significantly worse in diagnosing malignant lesions (75% for malignant lesions versus 91.3% for non-malignant lesions; p<0.0001). all of these analyses were assessed with regard to respondent demographic information, without any of these factors being statistically significant (gender, racial and ethnic identity, level of training, geographical location, presence of a dedicated skin of color clinic, and estimated proportion of patients with darker fitzpatrick skin types; all p>0.05). see table 2. among resident physician trainees, there is a gap in identification of skin cancer pathology among patients with darker skin types, in the context of an otherwise comparable results discussion skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 872 table 1. demographic information about respondents according to training year level. all % (n) pgy2 pgy3 pgy4 p value 1gender female male 53.0% (18) 47.0% (16) 64.3% (9) 35.7% (5) 33.3% (4) 66.7% (8) 62.5% (5) 37.5% (3) 0.24 2race asian black white other 14.3% (5) 8.6% (3) 71.4% (25) 5.7% (2) 14.3% (2) 14.3% (2) 57.1% (8) 14.3% (2) 16.7% (2) 8.3% (1) 75.0% (9) 0 11.1% (1) 0 88.9% (8) 0 0.69 2ethnicity hispanic/latino not hispanic/latino 8.6% (3) 91.4% (3) 7.1% (1) 92.9% (13) 8.3% (1) 91.7% (11) 11.1% (1) 88.9% (8) 0.99 2us region northeast southeast midwest southwest west 19.4% (7) 13.9% (5) 44.4% (16) 16.7% (6) 5.6% (2) 33.3% (5) 6.7% (1) 20.0% (3) 33.3% (5) 6.7% (1) 8.3% (1) 25.0% (3) 58.3% (7) 0 8.3% (1) 11.1% (1) 11.1% (1) 66.7% (6) 11.1% (1) 0 0.11 2setting rural urban 2.8% (1) 97.2% (36) 0 100% (15) 0 100% (12) 11.1% (1) 88.9% (8) 0.25 *quiz score overall mean, sd 84.3%, 6.1% 85.2%, 5.0% 83.7%, 4.9% 85.4%, 6.3% 0.72 quiz subscore, lighter skin mean, sd 85.4%, 11.4% 87.5%, 10.6% 85.4%, 9.0% 81.9%, 15.5% 0.53 quiz subscore, darker skin mean, sd 84.3%, 6.1% 83.8%, 5.7% 82.7%, 4.8% 87.3%, 7.8% 0.22 note: pgy: post graduate year [of training]. not all respondents provided answers to all questions. 1chi square 2fisher’s exact test *data shown are mean score percentage, standard deviation. anova was used to assess differences in scores skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 873 table 2. comparison of diagnostic accuracy. lighter skin darker skin t – test comparison comparison to measured variables 1st analysis: overall scores 85.4% 84.3% no significant difference no significant relationship 2nd analysis: scores on malignant lesions 100% 75% statistically significant difference (p <.0001) no significant relationship nonmalignant malignant t – test comparison comparison to measured variables 3rd analysis: scores on malignant lesions vs. nonmalignant lesions in skin of color 91.3% 75% statistically significant difference (p <.001) no significant relationship diagnostic accuracy for benign skin conditions. our findings fit with recent trends in dermatology graduate medical education that have focused on advancing physician knowledge of common cutaneous conditions that affect patients with darker skin types. skin cancer in contrast, is less common in patients with darker skin types, and thus may not be the target for curricular interventions at this time. our results are congruent with a 2022 study which identified that dermatology residents are more likely to biopsy nonmalignant lesions than malignant lesions of darker skin.10 while the national push for improved recognition and treatment for cutaneous diseases in darker skin types has improved for the average patient, such efforts may not yet translate into improved health equity nor health outcomes with regard to skin cancer. it thus remains of concern that some lesions may be misdiagnosed or delayed in diagnosis, yielding higher risk for morbidity and mortality. the social ecological model, one of the most widely used public health models, depicts health as a by-product of influential factors at the individual, interpersonal, institutional, and community levels.8 in this study, we attempted to understand the interpersonal level as a source of health disparities: the ability of dermatology physicians to diagnose conditions in patients with darker versus lighter skin tones. in our study, we did not find a statistically significant difference amongst comparison of quiz performance to any of the measured variables rules out the hypothesis that they may predict the resident’s visual diagnostic accuracy, notably including respondent demographic factors, presence skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 874 at a program with a dedicated skin of color clinic, or higher estimated proportion of patients with darker skin types. given that dermatology residents are generally wellequipped to accurately identify lesions regardless of skin type, other sources of this disparity must be considered. solutions to factors at the institutional and community levels, such as barriers to health insurance registration, barriers to traveling to medical appointments, and individual level barriers, such as individual health literacy, must be equally explored as potential intervention targets. while more work is yet to be done to enhance the therapeutic bond and fully optimize interpersonal interactions between patients and their physicians, healthcare professionals must not neglect the broader societal factors implicated in the development of health disparities in dermatology. strengths and limitations despite being open to all residents in acgme-accredited dermatology residency programs, our sample size was low in this exploratory study. this may have been due in part to survey dissemination to program administrators rather than directly to residents; some programs may have policies in place against survey participation solicitation from outside sources such as our study. the survey was also disseminated during the beginning of the medical academic year, which may have resulted in it being deprioritized due to the residents' changing responsibilities and rotations in the summer months. however, with our sample size we remained powered to detect large effect size, statistically significant differences (beta = 0.2, alpha = 0.05).11 while larger studies with alternative recruitment strategies remain needed, our study points to an alarming difference in diagnostic accuracy for malignant lesions in darker versus lighter skin types. given the known disparities in skin cancer survival for patients with darker versus lighter skin types, our study demonstrates that residency programs must emphasize identification of such lesions as part of our nation's overall efforts to improve skin cancer survival for individuals from all communities. the u.s census bureau projects that by 2050, over 50% of the u.s population will be a person of color (african american, hispanic, and asian americans).9 it is imperative now more than ever that efforts are being made to ensure the field of dermatology remains accessible and to mitigate the risk of widening of known health disparities among an increasingly diverse patient population. dermatologists should maintain a high clinical suspicion for malignant conditions in patients with darker skin types, given that these lesions are the most preferentially misdiagnosed and the fact that these lesions carry higher risks for morbidity and mortality. we commend the national efforts to advance health equity in the field of dermatology via curricular changes, and further recommend additional efforts to highlight cutaneous malignancies as a featured topic within such changes. acknowledgements: special permission for the use of these images and specific, explicit approval for the images included in this study has been granted by each of the partner organizations from which the images were taken, including visualdx, dermnet new zealand, and skindeep. we would like to thank all of these collaborators for their support. conflict of interest disclosures: none funding: none corresponding author: alissa jeanfreau, bs 2020 gravier street conclusion skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 875 new orleans, la 70112 phone: (504) 520-9261 email: ajean3@lsuhsc.edu references: 1. buster kj, stevens ei, elmets ca. dermatologic health disparities. dermatol clin. 2012;30(1):53-59. doi:10.1016/j.det.2011.08.002 2. gupta ak, bharadwaj m, mehrotra r. skin cancer concerns in people of color: risk factors and prevention. asian pacific j cancer prev. 2016;17(12):5257–5264. doi:10.22034/apjcp.2016.17.12.5257 3. guda va, paek sy. skin of color representation in commonly utilized medical student dermatology resources. j drugs dermatology. 2021;20(7):799. doi:10.36849/jdd.5726 4. mamo a, szeto md, rietcheck h, et al. evaluating medical student assessment of common dermatologic conditions across fitzpatrick phototypes and skin of color. j am acad dermatol. 2022;87(1):167-169. doi:10.1016/j.jaad.2021.06.868 5. gupta r, ibraheim mk, dao h, patel ab, koshelev m. assessing dermatology resident confidence in caring for patients with skin of color. clin dermatology. 2021;39(5):873-878. doi:10.1016/j.clindermatol.2021.08.019 6. fenton a, elliott e, shahbandi a, et al. medical students’ ability to diagnose common dermatologic conditions in skin of color. j am acad dermatol. 2020;83(3):957-958. doi:10.1016/j.jaad.2019.12.078 7. williams d, rhodes re. the confounded self-efficacy construct: review, conceptual analysis, and recommendations for future research. health psychol rev. 2016;10(2):113-128. doi:10.1080/17437199.2014.941998 8. bronfenbrenner u, ceci sj. nature-nurture reconceptualized in developmental perspective: a bioecological model. psychol rev. 1994;101(4):568-586. 9. vespa j, medina l, armstrong dam. demographic turning points for the united states: population projections for 2020 to 2060.; 2018. https://www.census.gov/content/dam/census /library/publications/2020/demo/p251144.pdf. 10. krueger l, hijab e, latkowski ja, elbuluk n. clinical decision-making bias in darker skin types: a prospective survey study identifying diagnostic bias in decision to biopsy [published online ahead of print, 2022 apr 6]. int j dermatol. 2022;10.1111/ijd.16213. doi:10.1111/ijd.16213 11. cohen j. a power primer. psychol bull. 1992;112(1):155-159. doi:10.1037//00332909.112.1.155 what’s new in the medicine chest? part 1 james del rosso, do video length: 25:03 video description: in a cme podium lecture presented at the 2017 fall clinical dermatology conference® in las vegas, nevada, james del ross, do, reviews recent advances in dermatopharmacology. topics highlighted include advances in photoprotection, atopic dermatitis, oral antibiotics, and rosacea. introduction • psoriasis is a chronic, systemic infl ammatory disease affecting 1% to 4% of the world’s population.1-3 • apremilast (apr), an oral, small-molecule phosphodiesterase 4 inhibitor, has been studied in phase 2 and phase 3 clinical trials in >2,000 adult patients with moderate to severe plaque psoriasis. • clinical trial data, however, do not fully provide insight into the effectiveness of apr at the patient level from populations that are refl ective of the demographically and clinically diverse patients treated at dermatology practices. • this study examined apr from the patient perspective in the dermatology practice setting, including prescribing patterns, clinical effectiveness, and patientperceived overall treatment effectiveness (pote) using modernizing medicine’s electronic medical record (emr) database of >550,000 psoriasis patients. methods study design • this was a multicenter, longitudinal, retrospective observational cohort study in adults with psoriasis in real-world dermatology practices across the united states. the study period was from october 1, 2014, through january 31, 2016. • structured data, de-identifi ed in accordance with hipaa, were collected from modernizing medicine’s emr platform. patient inclusion criteria • adults ≥18 years of age with a dermatologist-given psoriasis-specifi c diagnosis who at study initiation or at any time during the study period received apr, either alone or in combination. assessments and analysis • patient demographic and clinical characteristics at the most recent clinic visit were recorded; frequencies of psoriasis-related comorbidities were also determined. • effi cacy outcomes were evaluated among the subset of patients who received apr monotherapy and who had ≥2 effi cacy outcome data points during the study period: the fi rst at the time of initial apr prescription and ≥1 other within 6 months. • for effi cacy analyses of apr monotherapy, patients were stratifi ed according to whether they had received any prior conventional or biologic systemic treatment (naive/experienced). • effi cacy outcomes were examined using a linear mixed-effect model, adjusted for demographic characteristics and psoriasis-related comorbidities. • pote was examined among patients receiving apr monotherapy for ≥90 days; pote was scored on a 5-point likert scale, where 1=strongly agree and 5=strongly disagree in response to the following statement: “i believe this treatment is effective in clearing my skin of psoriasis.” the frequency of each response category was determined. results patients • a total of 7,517 patients were on apr at study initiation or during the study period; demographic and baseline clinical characteristics are summarized in table 1. • more than half of the patients (52.4%) had a psoriasis-related comorbidity (table 1). results (cont’d) table 1. baseline characteristics of patients prescribed apr characteristic apr patients n=7,517 age, mean (sd), years 52.3 (14.8) male, n (%) 3,611 (48.0) race/ethnicity, n (%) white 4,795 (63.8) african american 191 (2.5) asian 155 (2.1) hispanic 439 (5.8) other 422 (5.6) unknown 1,515 (20.2) comorbidity, n (%) arthritis 1,781 (23.7) cardiovascular disease 2,487 (33.1) depression 762 (10.1) diabetes 991 (13.2) hepatitis 152 (2.0) lymphoma 23 (0.3) note: some patients were recorded as having multiple comorbidities, and therefore are counted more than once. pattern of switching from other therapies to apr treatment • among the patients who changed from non-apr treatments to apr monotherapy during the study period, almost three-quarters (74.2%) changed from topical treatment alone to apr monotherapy (figure 1). • the majority of patients (>75%) who started on phototherapy, methotrexate, adalimumab, or ustekinumab and who received apr did so as add-on therapy to their ongoing treatment. figure 1. prior treatments in patients who switched to apr monotherapy 74.2 2.2 4.4 3.9 2.3 0.4 2.5 9.4 prior treatment (percentage of patients) topical acitretin methotrexate adalimumab etanercept secukinumab ustekinumab other data are based on the subset of patients who switched from non-apr treatment to apr monotherapy during the study period. effect of apr monotherapy on psoriasis-affected bsa • a total of 196 systemic-naive and 177 systemic-experienced patients on apr monotherapy met inclusion criteria for analysis of psoriasis-affected body surface area (bsa) scores (i.e., bsa values recorded at ≥2 visits during the study period). • in this patient subgroup, adjusted bsa scores signifi cantly decreased in both the systemic-naive patients (−11.12%; p<0.001) (a decrease from baseline of approximately 62.0%) and the systemic-experienced patients (−7.70%; p=0.002) (a decrease from baseline of approximately 60.0%) within 6 months of initiating apr monotherapy (figure 2). results (cont’d) figure 2. adjusted psoriasis-affected bsa during apr monotherapy systemic-naive 0 10 5 15 20 0 6 6 time (months) bs a (% ) 0 10 5 15 20 bs a (% ) 1 2 3 4 5 p<0.001 vs. apr baseline. systemic-experienced 0 1 2 3 4 5 time (months) p=0.002 vs. apr baseline. bsa scores were adjusted for demographic characteristics and psoriasis-related comorbidities. patient-perceived overall treatment effectiveness of apr monotherapy • among patients who received apr monotherapy for ≥90 days and had ≥1 pote assessment (n=160), the majority (n=138; 86%) somewhat agreed or strongly agreed that apr treatment was effective in clearing their skin of psoriasis (figure 3). figure 3. patient-perceived effectiveness of apr monotherapy strongly agreed somewhat agreed neither agreed nor disagreed somewhat or strongly disagreed 86% agreed or strongly agreed 7% 7%56% 30% percentage of patient responses to the statement, “i believe this treatment is effective in clearing my skin of psoriasis” responses were captured by providers asking patients to indicate level of agreement. conclusions • in this analysis of the us psoriasis population from dermatology clinical practices, apr signifi cantly reduced bsa within 6 months after treatment initiation, regardless of whether patients were systemic-naive or systemic-experienced. • most patients who switched to apr monotherapy had previously received only topical therapy. • the majority of patients included in the pote analysis perceived apr to be effective in clearing their psoriasis. references 1. helmick cg, et al. am j prev med. 2014;47:37-45. 2. rachakonda td, et al. j am acad dermatol. 2014;70:512-516. 3. parisi r, et al. j invest dermatol. 2013;133:377-385. acknowledgments the authors acknowledge fi nancial support for this study from celgene corporation. the authors received editorial support in the preparation of this report from amy shaberman, phd, of peloton advantage, llc, parsippany, nj, usa, sponsored by celgene corporation, summit, nj, usa. the authors, however, directed and are fully responsible for all content and editorial decisions for this poster. correspondence april armstrong – aprilarm@usc.edu disclosures aa: abbvie, janssen, lilly, modernizing medicine, novartis, pfi zer regeneron, and sanofi – grants, consulting fees, and/or honorarium. el: celgene corporation – employment. presented at: the 2017 fall clinical dermatology conference; october 12–15, 2017; las vegas, nv. a retrospective cohort study of real-world experience with apremilast in patients with plaque psoriasis april armstrong, md, mph1; eugenia levi, pharmd2 1university of southern california, keck school of medicine, los angeles, ca; 2celgene corporation, summit, nj fc17postercelgenearmstrongretrospectivecohort.pdf introduction • the assessment of achieving, sustaining, and improving clinical responses and low disease status with biologics in psoriatic arthritis (psa) are important parts of eular and grappa recommendations that aim to optimize treatment goals and improve patient quality of life1,2 • secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin (il)-17a, has demonstrated significant efficacy in the treatment of moderate to severe psoriasis3 and psa,4,5 demonstrating a rapid onset of action and sustained responses • in the phase 3 future 2 study (nct01752634), secukinumab provided sustained improvement in the signs and symptoms of active psa over 104 weeks6 • here, we present results at the individual patient-level on the efficacy of secukinumab at improving, sustaining, or worsening acr response and disease status (28-joint disease activity score using crp [das28-crp])-derived criteria from week 24 to 104 in patients with active psa in the future 2 study methods study design and patients • future 2 is an ongoing, phase 3, double-blind, randomized, placebo-controlled study4,6 – a total of 397 patients were randomized (1:1:1:1) to receive subcutaneous (s.c.) secukinumab (300, 150, or 75 mg) or placebo at weeks 0, 1, 2, 3, and 4 and once every 4 weeks thereafter. placebo-treated patients were re-randomized (1:1) to receive s.c. secukinumab (300 or 150 mg) at week 16 (non-responders) or week 24 (responders) based on clinical response • the key inclusion and exclusion criteria have been reported elsewhere4 endpoints and assessments • post-hoc analysis of data from patients with psa who were originally randomized to receive secukinumab 300 and 150 mg and completed the 16-week double-blind treatment period followed by long-term uncontrolled treatment • shift analyses were performed on acr responses between week 24 (primary endpoint) and week 104 (sustained effect). the sub-groups based on acr criteria included: – acr non-responders (acr nr) – acr20 responders – acr50 responders – acr70 responders • shift analyses were performed on das28-crp scores between week 24 and week 104. the das28-crp-derived criteria7 included: – high disease activity (hda; >5.1) – moderate disease activity (moda; >3.2 and ≤5.1) – low disease activity (lda; ≤3.2 and ≥2.6) – remission (rem; <2.6) • shift analyses were performed on psoriasis area and severity index (pasi) responses (pasi non-responder [pasi nr], pasi 75, and pasi 90) and minimal disease activity (mda) responses (mda non-responders [mda nr] and mda) between week 24 and week 104 statistical analyses • data are presented as observed in patients with data available at weeks 24 and 104 • the shift analyses were performed on acr, das28-crp, pasi, and mda responses between weeks 24 and 104 for subgroups of secukinumab-treated patients categorized by their highest response criteria at the earlier time point, by evaluating whether these responses were improved, sustained, or worsened at the later time point, using mutually exclusive response categories • a patient was classified as having achieved mda upon meeting at least five of the seven pre-defined criteria determining mda response8 results • in total, 86/100 (86%) and 76/100 (76%) patients receiving secukinumab 300 and 150 mg, respectively, completed 104 weeks of treatment6 – of these, 73/70, 81/75, 34/41, and 83/76 patients in secukinumab 300/150 mg were eligible for acr, das28-crp, pasi, and mda shift analyses, respectively, from week 24 to week 104 • patient disposition and baseline characteristics have been reported previously4 – the mean age of patients was 46.9 ± 12.6 and 46.5 ± 11.7 years, mean pasi score was 11.9 ± 8.4 and 16.2 ±14.3, psoriasis body surface area ≥3% was present in 41% and 58% of patients, and mean das28-crp score was 4.8 ± 1.0 and 4.9 ± 1.1 in the secukinumab 300 and 150 mg groups, respectively efficacy • in the secukinumab 300 and 150 mg groups, a majority (84% and 75%) of acr70 responders and acr50 responders (67% and 46%), respectively, either maintained or improved their response at week 104 (figure 1) figure 1. shift analysis of acr responses from week 24 to week 104 65 15.8 20 5.3 30 21.1 13.3 5.3 42.1 26.7 5.3 5 21.1 40 84.2 0 20 40 60 80 100 acr nr (n1 = 20) acr20 (n2 = 19) acr50 (n3 = 15) acr70 (n4 = 19) % r es po nd er s at w ee k 10 4 week 24 secukinumab 300 mg s.c. (n = 73) 73.9 14.3 7.7 5 17.4 57.1 46.2 15 4.3 21.4 23.1 5 4.3 7.1 23.1 75 0 20 40 60 80 100 acr nr (n1 = 23) acr20 (n2 = 14) acr50 (n3 = 13) acr70 (n4 = 20) week 24 secukinumab 150 mg s.c. (n = 70) acr nr acr20 acr50 acr70 n = number of patients who completed week 104 and had acr response available at both weeks 24 and 104; n1 = number of patients with no acr response at week 24 who completed week 104 and had acr response available; n2–n4 = number of patients with acr response at week 24 who completed week 104 and had acr response available • in the secukinumab 300 mg group, 53% of patients with lda improved to rem and a majority (76%) of patients with rem maintained their status from week 24 to 104, whereas in the secukinumab 150 mg group, a majority (75% and 72% with lda and rem, respectively) of patients improved or maintained their status at week 104 (figure 2) figure 2. shift analysis of das28-crp status from week 24 to week 104 4 75 60 20 5.4 12 26.7 18.9 25 24 53.3 75.7 0 20 40 60 80 100 hda (n1 = 4) moda (n2 = 25) lda (n3 = 15) rem (n4 = 37) % r es po nd er s at w ee k 10 4 week 24 secukinumab 300 mg s.c. (n = 81) 50 3.2 12.5 25 58.1 12.5 9.4 25.8 18.8 25 12.9 75 71.9 0 20 40 60 80 100 hda (n1 = 4) moda (n2 = 31) lda (n3 = 8) rem (n4 = 32) week 24 secukinumab 150 mg s.c. (n = 75) hda moda lda rem n = number of patients who completed week 104 and had das28-crp response available at both weeks 24 and 104; n1 = number of patients with no das28-crp response at week 24 who completed week 104 and had das28-crp response available at both time points; n2–n4 = number of patients with das28-crp at week 24 who completed week 104 and had das28-crp response available. das28-crp status was calculated with validated cut-offs to indicate hda (>5.1), moda (>3.2 and ≤5.1), lda (≤3.2 and ≥2.6), and rem (<2.6)7 • a majority (86% and 58%) of mda responders at week 24 maintained their response at week 104 in both secukinumab 300 and 150 mg groups, respectively. a total of 21% and 12% of mda nr at week 24 developed a response at week 104 in both secukinumab 300 and 150 mg groups, respectively (figure 3) figure 3. shift analysis of mda response from week 24 to week 104 78.7 13.6 21.3 86.4 0 20 40 60 80 100 mda nr (n1 = 61) mda (n2 = 22) % r es po nd er s at w ee k 10 4 week 24 secukinumab 300 mg s.c. (n = 83) 87.7 42.1 12.3 57.9 0 20 40 60 80 100 mda nr (n1 = 57) mda (n2 = 19) week 24 secukinumab 150 mg s.c. (n = 76) mda nr mda n = number of patients who completed week 104 and had mda data available at both weeks 24 and 104; n1 = number of patients not achieving mda at week 24 who completed week 104 and had mda data available at both weeks 24 and 104; n2 = number of patients achieving mda at week 24 who completed week 104 and had mda data available at both weeks 24 and 104 • in the secukinumab 300 and 150 mg groups, a majority (100% and 78%, respectively) of pasi 90 responders maintained their status at week 104, whereas 50% and 56% of pasi 75 responders, respectively, improved their response to pasi 90 at week 104 (figure 4) summary of results • most secukinumab-treated patients who achieved at least an acr50/70 or pasi response at week 24 improved or sustained their response at week 104 • the majority of mda responders at week 24 treated with secukinumab 300 mg sustained their response at week 104 • the majority of patients who were in the moda, lda, or rem status related to das28-crp score at week 24 sustained or improved their disease status at week 104 figure 4. shift analysis of pasi response (psoriasis body surface area ≥3%) from week 24 to week 104 55.6 33.3 22.2 16.7 22.2 50 100 0 20 40 60 80 100 pasi nr (n1 = 9) pasi 75 (n2 = 6) pasi 90 (n3 = 19) % r es po nd er s at w ee k 10 4 week 24 secukinumab 300 mg s.c. (n = 34) 42.9 33.3 5.6 35.7 11.1 16.7 21.4 55.6 77.8 0 20 40 60 80 100 pasi nr (n1 = 14) pasi 75 (n2 = 9) pasi 90 (n3 = 18) week 24 secukinumab 150 mg s.c. (n = 41) pasi nr pasi 75 pasi 90 n = number of patients who completed week 104 and had pasi response available at both weeks 24 and 104; n1 = patients with no pasi score at week 24 who completed week 104 and had pasi scores available at both weeks 24 and 104; n2 and n3 = number of patients achieving pasi 75 and pasi 90, respectively, at week 24 who completed week 104 and had pasi score available at both weeks 24 and 104 conclusions • improvements in individual acr and pasi responses and disease status observed with secukinumab at week 24 were sustained or improved further through 2 years in a majority of patients with psa • sustainability of responses on more stringent efficacy criteria such as acr70 and mda were numerically higher with secukinumab 300 mg, extending the results previously reported at group level4,6 secukinumab sustains individual clinical responses over time in patients with psoriatic arthritis: 2-year results from a phase 3 trial p emery1, ib mcinnes2, pj mease3, m schiff4, l pricop5, s shen5, z wang5, c gaillez6; on behalf of the future 2 study group 1leeds teaching hospitals nhs trust, leeds, uk; 2university of glasgow, glasgow, uk; 3swedish medical center and university of washington, seattle, wa, usa; 4university of colorado, denver, co, usa; 5novartis pharmaceuticals corporation, east hanover, nj, usa; 6novartis pharma ag, basel, switzerland. download document at the following url: http://novartis.medicalcongressposters.com/default.aspx?doc=ff5c0 and via text message (sms) text: qff5c0 to: 8nova (86682) us only +18324604729 north, central and south americas; caribbean; china +447860024038 uk, europe & russia +46737494608 sweden, europe scan to download a reprint of this poster references 1. gossec l, et al. ann rheum dis. 2016;75:499–510. 2. coates lc, et al. j rheumatol. 2014;41:1237–9. 3. langley rg, et al. n engl j med. 2014;371:326–38. 4. mcinnes ib, et al. lancet. 2015;386:1137–46. 5. mease pj, et al. n engl j med. 2015;373:1329–39. 6. mcinnes ib, et al. rheumatology. 2017;doi:10.1093/rheumatology/kex301. 7. wells g, et al. ann rheum dis. 2009;68:954–60. 8. coates lc, et al. ann rheum dis. 2010;69:48–53. disclosures p emery: consultant for abbvie, bms, merck, novartis, pfizer, roche, ucb. i mcinnes: consultant for novartis, amgen, janssen, bms, pfizer, ucb, abbvie, celgene, lilly. p mease: grant/research support from abbvie, amgen, bms, celgene, janssen, lilly, merck, novartis, pfizer, sun, ucb; consultant for abbvie, amgen, bms, celgene, crescendo bioscience, genentech, janssen, lilly, merck, novartis, pfizer, sun, ucb; speakers’ bureau for abbvie, amgen, bms, celgene, genentech, janssen, lilly, merck, novartis, pfizer, ucb. m schiff: consultant for abbvie, bms, lilly, j&j; speakers’ bureau for abbvie. l pricop, c gaillez: shareholders and employees of novartis. s shen, z wang: employees of novartis. acknowledgements the authors thank the patients and their families and all investigators and their staff for participation in the study. oxford pharmagenesis, inc., newtown, pa, usa provided assistance with layout and printing the poster; this support was funded by novartis pharmaceuticals corporation, east hanover, nj. the authors had full control of the contents of this poster. this research was funded by novartis pharma ag, basel, switzerland. poster presented at: 13th annual winter clinical dermatology conference, maui, hi, usa; january 12–17, 2018. reprinted from the 2017 acr/arhp annual meeting held november 3‒8, 2017. the american college of rheumatology does not guarantee, warrant, or endorse any commercial products or services. reprinted by novartis pharmaceuticals corporation. skin may 2019 volume 3 issue 3 copyright 2018 the national society for cutaneous medicine 223 short communications myeloid sarcoma – a case report vamsi varra, bs1, marla rodriguez, bs1, brandon t beal, md2, anthony p fernandez, md, phd2,3 1case western university school of medicine, case western reserve, cleveland, oh 2department of dermatology, cleveland clinic foundation, cleveland, oh 3department of dermatology, department of anatomic pathology, cleveland clinic foundation, cleveland, oh the diagnosis of myeloid sarcoma is challenging due to its rarity and heterogeneity of presentation. it can affect any organ and present at any age, although one of the more commonly involved sites is the skin. we present a unique case of isolated myeloid sarcoma that presented as generalized erythematous nodules involving the face, neck, chest, abdomen, back, and extremities. a 76-year-old male with a four-year history of idiopathic thrombocytopenia on no medications presented with acute onset generalized erythematous nodules worsening over 7-weeks. review of symptoms was remarkable for myalgias (shoulders/thighs), unintentional 9lbs weight loss, and lower lip numbness. physical examination revealed innumerable plumcolored 5-20mm nodules involving the face, neck, chest, abdomen, back, and extremities (figure 1). no palpable lymphadenopathy was appreciated. a skin biopsy was performed from a 1cm nodule on the left arm (figure 2a). histologic sections revealed a dense dermal infiltrate of medium-sized mononuclear cells with finely dispersed chromatin, small nucleoli, increased nuclear:cytoplasmic ratio, and irregular nuclear contours (figure 2a). staining was positive for cd43 (figure 2b), lysozyme (muramidase) (figure 2c), cd33, cd56, and cd45. staining was negative for cd3, cd4, cd20, cd34, cd68 (pg-m1), cd117, cd 123, cd163, myeloperoxidase, tdt, and pax-5. bone marrow biopsy demonstrated hypercellular bone marrow with granulocytic/ megakaryocytic hyperplasia, and dysgranulopoiesis. peripheral blood smear figure 1: 76 year old male presenting with an eruption of innumerable plum-colored nodules. introduction case report skin may 2019 volume 3 issue 3 copyright 2018 the national society for cutaneous medicine 224 figure 2: histologic sections of skin biopsy taken from a 1cm nodule on the left arm: a, stained with hematoxylin and eosin. b, stained positive for cd43. c, stained positive for lysozyme. showed left-shifted neutrophilia, with no morphological evidence of acute leukemia. flow cytometry on peripheral blood was unremarkable. qrt-pcr studies performed on bone marrow aspirate ruled out bcr-abl positive chronic myelogenous leukemia (cml). testicular ultrasound revealed leukemic infiltrates. the histopathologic and bone marrow biopsy findings were consistent with a diagnosis of myeloid sarcoma (ms). the differential diagnosis for cutaneous ms includes b-cell lymphoma, acute myeloid leukemia (aml), cutaneous t-cell lymphoma, ewing sarcoma, melanoma, round blue cell tumors, and poorly differentiated carcinoma. ms is an extramedullary tumor of myeloblasts most often associated with aml (incidence 2.5%-9.1%).1 common sites of involvement include the skin and lymph nodes, followed by testes, bone, peritoneum, and gastrointestinal tract.1, 2 there is no age predilection (range 1 – 81 years). clinically, the tumors vary in size (1-20 mm) and symptoms are typically due to compression (pain or bleeding).3 the diagnosis of ms is established through immunophenotyping. common positive immunohistochemical markers are cd43, cd68, lysozyme, myeloperoxidase, and cd117.2,4,5 peripheral smear, flow cytometry, and bone marrow biopsy (bmb) are needed to categorize the disease and determine the extent of involvement. in our patient, peripheral blood smear, flow cytometry, and bmb were essential for excluding aml and cml, as well as other leukemias and lymphomas. the literature on ms is limited to case reports and small retrospective studies, preventing the development of optimal therapeutic approaches. in the studies available, ms is generally treated with aml chemotherapy regimens and for select patients allogeneic hematopoietic stem cell transplant (hsct).3 however, in older patients such as our patient, hsct and intensive chemotherapy are poorly tolerated, necessitating different strategies, such as treatment with 5azacytidine.1 discussion skin may 2019 volume 3 issue 3 copyright 2018 the national society for cutaneous medicine 225 the diagnosis of myeloid sarcoma is challenging due to its rarity and heterogeneity of presentation, it can affect any organ and present at any age. ms is a histological diagnosis necessitating immunophenotyping. the tumor most commonly stains positive for cd43, cd68, lysozyme, and myeloperoxidase. while optimal treatment regimens for ms are not known, systemic aml chemotherapy regimens have been shown to prolong disease free survival and improve quality of life for patients. conflict of interest disclosures: none. funding: none. corresponding author: marla rodriguez case western reserve university school of medicine cleveland, oh mar238@case.edu references: 1. katagiri t, ushiki t, masuko m, et al. successful 5-azacytidine treatment of myeloid sarcoma and leukemia cutis associated with myelodysplastic syndrome: a case report and literature review. medicine (baltimore) 2017;96:e7975. 2. almond lm, charalampakis m, ford sj, et al. myeloid sarcoma: presentation, diagnosis, and treatment. clin lymphoma myeloma leuk 2017;17:263-267. 3. avni b, koren-michowitz m. myeloid sarcoma: current approach and therapeutic options. ther adv hematol 2011;2:309-16. 4. yamauchi k, yasuda m. comparison in treatments of nonleukemic granulocytic sarcoma: report of two cases and a review of 72 cases in the literature. cancer 2002;94:1739-46. 5. paydas s, zorludemir s, ergin m. granulocytic sarcoma: 32 cases and review of the literature. leuk lymphoma 2006;47:2527-41. conclusion mailto:mar238@case.edu presented at the 40th annual fall clinical dermatology conference (fall cdc 2020); virtual congress; october 29 – november 1, 2020 introduction • children with severe atopic dermatitis (ad) have limited treatment options with an acceptable benefit–risk profile1–3 – systemic corticosteroids are strongly discouraged in children4 – other systemic agents are used off-label and do not have an acceptable benefit–risk profile for children who use these therapies on a long-term basis5 • dupilumab, a fully human monoclonal antibody,6,7 blocks the shared receptor component for interleukin (il)-4 and il-13, thus inhibiting signaling of both il-4 and il-13, key cytokines involved in atopic diseases such as ad • adolescents with moderate-to-severe ad who received dupilumab in a phase 2a study and continued in an open-label extension (ole) phase 3 study showed improvement in ad signs with an acceptable safety profile with over 52 weeks of total treatment8 objective • here we report dupilumab pharmacokinetics (pk), safety, and efficacy in children aged ≥ 6 to < 12 years who participated in the phase 2a study, and then continued into the phase 3 ole study dupilumab provides acceptable long-term safety and efficacy in children aged ≥ 6 to < 12 years with uncontrolled, severe atopic dermatitis: results from patients who participated in an open-label phase 2a study and then in a subsequent phase 3 open-label extension study michael j. cork1, diamant thaçi2, lawrence f. eichenfield3,4, peter d. arkwright5, zhen chen6, mohamed a. kamal6, john t. o’malley7, ashish bansal6 1sheffield dermatology research, university of sheffield, sheffield, uk; 2university of lübeck, lubeck, germany; 3university of california, san diego, ca, usa; 4rady children’s hospital, san diego, ca, usa; 5university of manchester, manchester, uk; 6regeneron pharmaceuticals, inc., tarrytown, ny, usa; 7sanofi, cambridge, ma, usa conclusion • safety and efficacy results support the use of dupilumab as a continuous long-term treatment for children aged ≥ 6 to < 12 years with severe ad references: 1. wollenberg a, et al. j eur acad dermatol venereol 2016;30:729-47. 2. sidbury r, et al. j am acad dermatol 2014;71:327-49. 3. ring j, et al. j eur acad dermatol venereol. 2012;26:1176-93. 4. drucker am, et al. br j dermatol. 2018; 178:768-75. 5. totri cr, et al. j am acad dermatol. 2017; 76:281-5. 6. macdonald le, et al. proc natl acad sci u s a. 2014;111:5147-52. 7. murphy aj, et al. proc natl acad sci u s a. 2014;111:5153-8. 8. cork mj, et al. br j dermatol. 2020;182:85-96. acknowledgments: research sponsored by sanofi and regeneron pharmaceuticals, inc. clinicaltrials.gov identifiers: nct02407756, nct02612454. medical writing/editorial assistance provided by luke shelton, phd, of excerpta medica, funded by sanofi genzyme and regeneron pharmaceuticals, inc. patients were recruited to the clinical trial in manchester, uk with the support of the nihr manchester clinical research facility, royal manchester children’s hospital, uk. partial phase 2a data were previously reported as a late-breaking presentation at the 2017 annual american academy of dermatology meeting (orlando, fl, usa; march 3–7, 2017). disclosures: cork mj: abbvie, astellas, boots, dermavant, galapagos, galderma, hyphens pharma, johnson & johnson, leo pharma, l’oréal, menlo therapeutics, novartis, oxagen, pfizer, procter & gamble, reckitt benckiser, regeneron pharmaceuticals, inc., sanofi genzyme – investigator, consultant. thaçi d: abbvie, almirall, ds-pharma, eli lilly, galapagos, galderma, leo pharma, morphosys, novartis, pfizer, regeneron pharmaceuticals, inc., sanofi – research support; abbvie, novartis – independent advisor honoraria; abbvie, beiersdorf, ds-pharma, galapagos, morphosys, novartis, pfizer, regeneron pharmaceuticals, inc., sanofi – consultant; abbvie, eli lilly, leo pharma, novartis, pfizer, regeneron pharmaceuticals, inc., sanofi – advisory board fees. eichenfield lf: almirall, dermavant, dermira, eli lilly, galderma, incyte, leo pharma, novartis, otsuka, pfizer, regeneron pharmaceuticals, inc., sanofi genzyme, valeant/ortho derm – consultant fees; abbvie, dermavant, dermira, eli lilly, galderma, incyte, medimetriks, pfizer, regeneron pharmaceuticals, inc., sanofi genzyme, valeant – study support (to institution). arkwright pd: sanofi genzyme – advisory board member, project grant funding. chen z, kamal ma, bansal a: regeneron pharmaceuticals, inc. − employees and shareholders. o’malley jt: sanofi − employee, may hold stock and/or stock options in the company. methods study design • the first study was a phase 2a, multicenter, open-label, ascending dose, sequential cohort study (nct02407756) – the study had 2 treatment parts: in part a, patients received a single dose of dupilumab (2mg/kg or 4mg/kg), followed by an 8-week follow-up sampling period for systemic drug concentration without treatment; this was followed by part b, where patients received 4 weekly (qw) doses, followed by an 8-week safety follow-up period (figure 1a) – an initial cohort of adolescents (aged ≥ 12 to < 18 years) with moderate-to-severe ad was enrolled; upon safety review of part a, a cohort of children (aged ≥ 6 to < 12 years) was enrolled for the corresponding dose group (figure 1a) • the second study is an ongoing, phase 3, ole study (nct02612454) enrolling pediatric patients who participated in previous dupilumab ad trials (figure 1b) – patients with a serious treatment-emergent adverse event (teae) deemed related to the study drug or with a teae related to study drug which led to discontinuation were not eligible to enroll in the ole study – patients continued on their original assigned regimen (2 mg/kg or 4 mg/kg qw) • here we present data from the patient population consisting of children who continued from the phase 2a study and received their original assigned regimen (2 mg/kg qw or 4 mg/kg qw, up to a maximum of 300 mg) in the ole study endpoints • primary endpoints – concentration–time profile (phase 2a study) of dupilumab, including pk parameters such as the area under the concentration time curve from 0 to the last measurable concentration (auclast), maximal concentration (cmax), and time to cmax (tmax) – incidence and rate of adverse events (phase 3 ole study) completion of phase 2a study baseline a b end of treatment end of study screening period screening visit between d –28 and d –1 phone visits at w1, w2, w3 weekly telephonic appraisalsc between in-clinic visitsd treatment period follow-up period w4 w260 w272w52d1 1st dose part aa safety review of data up to 2 weeks from the first 8 patients in cohort 1a cohort 1a (2 mg/kg in age group ≥ 12 to < 18 years) part bb 2 mg/kg part aa safety review of data up to 2 weeks from the first 20 patients in cohort 1a/1b cohort 1b (2 mg/kg in age group ≥ 6 to < 12 years) part bb part aa safety review of data up to 2 weeks from the first 8 patients in cohort 2a cohort 2a (4 mg/kg in age group ≥ 12 to < 18 years) part bb 4 mg/kg part aa cohort 2b (4 mg/kg in age group ≥ 6 to < 12 years) part bb final analysis figure 1. study design for the phase 2a study (a) and ole study (b). apart a: single dose followed by an 8-week follow-up period with semi-dense sampling for systemic drug concentration. bpart b: 4 weekly doses followed by an 8-week safety follow-up period. con visits in which study drug administration was planned, patients had the option to come to the clinic to have study drug administered by site staff. din-clinic visits occurred every 3 months. d, day; w, week. dupilumab 2 mg/kg dupilumab 4 mg/kg −91.87 −84.34 –100 –80 –60 –40 –20 0 20 0 4 8 12 16 20 0 4 8 12 16 20 24 28 32 36 40 44 48 52 study week phase 2a phase 3 ole % c h a n g e f ro m b a s e lin e in e a s i, m e a n ( ± s d ) a b c 76.5 25.0 0 10 20 30 40 50 60 70 80 90 100 0 4 8 12 16 20 0 4 8 12 16 20 24 28 32 36 40 44 48 52 phase 3 ole study week phase 2a p a ti e n ts a c h ie vi n g i g a 0 o r 1 ( % ) −69.86 −57.51 –100 –80 –60 –40 –20 0 20 40 60 80 100 0 4 8 12 16 20 0 4 8 12 16 20 24 28 32 36 40 44 48 52 phase 3 ole study week phase 2a % c h a n g e f ro m b a s e lin e in p e a k p ru ri tu s n r s , m e a n ( ± s d ) figure 3. efficacy assessment. mean percent change from baseline in easi (a); mean percent change from baseline in peak pruritus nrs (b); and proportion of patients achieving iga scores of 0 or 1 (c). dupilumab 2 mg/kg dupilumab 4 mg/kg 0.01m e a n ( ± s d ) d u p ilu m a b c o n c e n tr a ti o n ( m g /l ) a 0.10 1.00 10.00 100.00 1,000.00 0 4 8 12 16 20 study week lloq/2 b m e a n ( ± s d ) d u p ilu m a b c o n c e n tr a ti o n ( m g /l ) 0.01 0.10 1.00 10.00 100.00 1,000.00 0 4 20 248 28 32 3612 40 4416 48 study week lloq/2 figure 2. concentration–time profiles of dupilumab in the phase 2a study (a) and phase 3 ole study (b). vertical arrows represent timepoints when dupilumab was administered. lloq, lower limit of quantitation. results (cont.)methods (cont.) table 1. baseline demographics and disease characteristics. phase 2a study phase 3 ole study dupilumab 2 mg/kg (n = 18) dupilumab 4 mg/kg (n = 19) dupilumab 2 mg/kg (n = 17) dupilumab 4 mg/kg (n = 16) age, mean (sd), years 8 (2) 8 (2) 9 (2) 8 (2) male sex, n (%) 9 (50) 11 (58) 8 (47) 9 (56) bmi, mean (sd), kg/m2 17.5 (2.8) 16.8 (2.0) 16.9 (3.0) 17.0 (2.2) duration of ad, mean (sd), years 7 (2) 7 (2) 7 (3) 8 (2) easi, mean (sd) 33 (16) 39 (19) 21 (18) 32 (20) iga, n (%) iga = 3 1 (6)a 0 9 (53) 7 (44) iga = 4 17 (94) 19 (100) 4 (24) 8 (50) peak pruritus nrs, mean (sd) 6 (2) 7 (2) 6 (3) 6 (2) percent bsa affected, mean (sd) 59 (22) 62 (30) 37 (27) 50 (31) any previous non-corticosteroid immunosuppressants, n (%) 3 (17) 7 (37) n/a n/a patients with comorbid atopic allergic conditions, n (%) 14 (78) 17 (90) n/a n/a allergic rhinitis 9 (50) 10 (53) n/a n/a food allergy 10 (56) 14 (74) n/a n/a asthma 7 (39) 9 (47) n/a n/a allergic conjunctivitis 3 (17) 5 (26) n/a n/a chronic rhinosinusitis 0 1 (5) n/a n/a urticaria 1 (6) 0 n/a n/a other allergies 12 (67) 12 (63) n/a n/a a1 patient from this age group enrolled in the study had a baseline disease severity of iga = 3 but was still included in the analyses sets. bmi, body mass index; bsa, body surface area; n/a, not applicable; sd, standard deviation. table 2. safety assessment. phase 2a study phase 3 ole study dupilumab 2 mg/kg (n = 18) dupilumab 4 mg/kg (n = 19) dupilumab 2 mg/kg (n = 17) dupilumab 4 mg/kg (n = 16) dupilumab 2 mg/kg (n = 17) dupilumab 4 mg/kg (n = 16)part a part b part a part b patients with teaes n (%) n (%) np/100 py any teae 9 (50) 10 (56) 16 (84) 17 (89) 16 (94) 16 (100) 266 471 any serious teae 0 0 2 (11) 0 2 (12) 3 (19) 6 11 teaes related to treatment 0 1 (6) 3 (16) 3 (16) 4 (24) 2 (13) 13 7 teaes leading to discontinuation 0 0 0 0 0 0 0 0 any infection (soc) 6 (33) 8 (44) 10 (53) 12 (63) 12 (71) 15 (94) 98 209 skin infection (hlt) 1 (6) 1 (6) 7 (37) 5 (26) 5 (29) 6 (38) 17 25 non-herpetic skin infection (adjudicated) 1 (6) 1 (6) 6 (32) 5 (26) 4 (24) 3 (19) 12 11 herpes viral infection (hlt) 1 (6) 0 1 (5) 0 2 (12) 4 (25) 6 15 injection-site reaction (hlt) 0 0 1 (5) 1 (5) 2 (12) 1 (6) 5 3 conjunctivitisa 0 0 1 (5) 2 (11) 2 (12) 5 (31) 5 21 most common teaes (pt)b nasopharyngitis 3 (17) 4 (22) 6 (32) 4 (21) 8 (47) 9 (56) 35 37 dermatitis atopic 4 (22) 4 (22) 5 (26) 3 (16) 5 (29) 2 (13) 16 7 cough 0 1 (6) 5 (26) 3 (16) 2 (12) 5 (31) 6 20 dermatitis infected 1 (6) 0 3 (16) 2 (11) 2 (12) 0 5 0 headache 0 1 (6) 2 (11) 1 (5) 4 (24) 2 (13) 13 7 upper respiratory tract infection 0 1 (6) 0 1 (5) 2 (12) 4 (25) 6 16 herpes simplex 0 0 0 0 0 4 (25) 0 15 aincludes meddra conjunctivitis allergic, conjunctivitis bacterial, conjunctivitis, conjunctivitis viral, atopic keratoconjunctivitis. bincludes all meddra pts reported in ≥ 15% or ≥ 20% of patients in any treatment group of the phase 2a study or ole, respectively. hlt, meddra high level term; meddra, medical dictionary for regulatory activities; np/100 py, number of patients with ≥ 1 event per 100 patient-years; pt, meddra preferred term; soc, meddra system organ class. – mean pruritus scores showed moderate or severe pruritus at the baseline of the phase 2a study – a significant proportion of patients received systemic non-steroidal immunosuppressants prior to the baseline of the phase 2a study – most patients had other concomitant allergic diseases, including asthma, allergic rhinitis, and food allergies pk assessment • following a single subcutaneous dose of dupilumab on day 1 of the phase 2a study, auclast calculated from the mean concentration–time profile in serum was 160 day⋅mg/l and 330  day⋅mg/l for the 2 and 4 mg/kg groups, respectively – in the 2 mg/kg group, tmax was observed at 2 days after dosing with a cmax (± sd) of 14.3 mg/l (5.9), while in the 4 mg/kg group, tmax was observed 4 days after dosing with a cmax (± sd) of 32.4 mg/l (7.0) (figure 2a) • in the ole study, steady-state dupilumab trough mean (± sd) concentrations at weeks 24–48 ranged from 61.3 mg/l (35.0) to 76.8 mg/l (35.8) in the 2 mg/kg qw group and 143 mg/l (40.3) to 181 mg/l (65.9) in the 4 mg/kg qw group (figure 2b) • the overall pk profile was comparable to that seen in adults and adolescents, and characterized by nonlinear, target-mediated kinetics safety • phase 2a study (table 2) • secondary endpoints (phase 2a and phase 3 ole study) – percent change from baseline in eczema area and severity index (easi) – percent change in peak pruritus numerical rating scale (nrs) – proportion of patients achieving an investigator’s global assessment (iga) score of 0 or 1 analysis • pk, safety, and efficacy variables were summarized descriptively – the analysis set for all statistical analyses for both studies included all patients who received any study drug – patients in the pk population had to have ≥ 1 non-missing functional dupilumab result following the first dose of the study drug; only observed data were used for pk analyses, and data were set to missing if pk drug concentrations were not available • for phase 2a efficacy analyses, data after rescue treatment use during part b were set to missing – missing values during the first 4-week repeat-dose treatment period of part b up to end-of-treatment visit were imputed by the last observation carried forward method; after the end of treatment in part b, no imputation of missing data was made • for the phase 3 ole, an all-observed method was employed, regardless of whether rescue treatment was used or data were collected after withdrawal from study treatment; no missing values were imputed results • 37 children completed the phase 2a study (the safety analysis set), of whom 33 continued to the ole • baseline demographic and disease characteristics are shown in table 1 – the majority of reported teaes in the phase 2a study were of mild or moderate severity; 14% patients reported a severe teae – 2 (5%) patients experienced a serious teae, both in the 4 mg/kg dose group during part a, with the serious adverse events deemed unrelated to dupilumab – there were no permanent treatment discontinuations due to teaes – the most frequent teaes were nasopharyngitis and ad exacerbation • in the phase 3 ole (table 2) – 2 (12%) and 3 (19%) patients reported ≥ 1 serious teae in the 2 mg/kg and 4 mg/kg dose groups, respectively; none of these events were related to treatment, and none led to discontinuation of study drug – the most common teaes were nasopharyngitis and ad exacerbation – conjunctivitis was reported in a total of 7 patients: 2 (12%) and 5 (31%) in the 2 mg/kg and 4 mg/kg groups, respectively • dupilumab treatment for up to 52 weeks was well tolerated with a acceptable safety profile consistent with the known dupilumab safety profile from studies in adolescents and adults with moderate-tosevere ad efficacy • mean easi improved at week 2 of the phase 2a, after a single dupilumab dose, and continued to improve through to week 52 of ole (figure 3a) • mean nrs improved at week 2 (phase 2a with improvements seen through week 52 of ole (figure 3b) • by week 12 of the phase 2a study, 17% and 21% patients in the 2 and 4 mg/kg groups, respectively, achieved iga 0/1, with proportions further increasing to 76% and 25%, respectively, at week 52 of ole (figure 3c) • some loss of efficacy is observed between weeks 48 and 52 due to 3 patients in the 4 mg/kg group temporarily discontinuing dupilumab • ad signs and symptoms, including pruritus, showed rapid improvements with single-dose dupilumab in the phase iia study. improvements in clinical scores (easi, scorad) and peak pruritus nrs were observed as early as week 2, with further improvement on continued treatment up to week 52 in the ole skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 945 skinmages vesiculobullous erythema migrans with central necrosis julian stashower, ba1, abigail wills, md2, barrett zlotoff, md2,3 1university of virginia school of medicine, charlottesville, va 2department of dermatology, university of virginia school of medicine, charlottesville, va 3department of pediatrics, university of virginia school of medicine, charlottesville, va a 35-year-old male with no prior medical history presented with a three-day history of an expanding annular rash on his upper back. he reported that the rash had become increasingly painful, as well as new onset of systemic symptoms including fevers, chills, fatigue, and arthralgias. he lived in a wooded area but denied any known tick exposure. physical exam revealed a large, erythematous targetoid patch with central necrotic bullae on his mid-upper back. the patient’s presentation was consistent with bullous lyme disease and he was started on a four-week course of doxycycline. several hours following his initial dose of doxycycline, he noted worsening of fevers and chills, rigors, and myalgias consistent with jarisch herxheimer reaction. at four-day follow-up he described near resolution of systemic symptoms, with sloughing and increased necrosis of his rash. skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 946 lyme disease is most commonly reported in the summer months and is caused by the spirochete borrelia burgdorferi. it is primarily transmitted through the ixodes tick and is the most prevalent tick-borne disease in north america, europe, and parts of eastern asia. lyme disease typically presents with erythema migrans at the site of inoculation and a flu-like illness. the most common appearance of erythema migrans is annular, expanding erythema, however the clinical presentation may vary. ulceration, central hemorrhage, or necrosis may be exhibited, the rash may not have stereotypical central clearing, and a vesiculobullous component may be found in up to 8% of cases.1,2 findings of vesicles or bullae may represent a strong immune response to the tick bite itself. when presenting atypically, the differential diagnosis may expand to include varicella zoster, herpes simplex, arthropod bite, sweet syndrome, and necrotizing fasciitis. diagnosis of lyme disease is primarily clinical, as histopathologic findings are nonspecific and serologic tests, culture, and polymerase chain reaction have poor sensitivities, especially in the acute phase of the disease. patient history may not be helpful towards this end, as many patients do not recall tick exposure and ticks may attach to bodily regions that are not visible to the patient. thus, clinical recognition of erythema migrans is essential to prevent delayed diagnosis and potentially severe cardiac, neurologic, and rheumatologic sequelae. notably, a jarisch-herxheimer reaction may occur early in the treatment course and may cause an increase in systemic symptoms and worsening of cutaneous disease.3,4 this case highlights a seldom-seen form of cutaneous lyme disease. familiarity with the numerous morphologic variants of erythema migrans is vital to accurate identification and timely initiation of treatment. lyme disease itself is common and clinicians should maintain a high index of suspicion in patients with the appropriate clinical context. additionally, dermatologists should have a low threshold for starting empiric treatment in patients with suspected lyme disease in order to avoid long-term complications. conflict of interest disclosures: none funding: none corresponding author: julian stashower, b.a. university of virginia school of medicine 1215 lee street, charlottesville, virginia 22908 email: jas2wf@virginia.edu references: 1. bhate c, schwartz ra. lyme disease: part i. advances and perspectives. j am acad dermatol. 2011;64(4):619-636; quiz 637-638. doi:10.1016/j.jaad.2010.03.046 2. goldberg ns, forseter g, nadelman rb, et al. vesicular erythema migrans. arch dermatol. 1992;128(11):1495-1498. 3. doughty h, o’hern k, barton dt, carter jb. vesiculobullous lyme disease: a case series. jaad case rep. 2022;24:56-58. doi:10.1016/j.jdcr.2022.04.001 4. paul s, song pi, ogbechie oa, et al. vesiculobullous and hemorrhagic erythema migrans: uncommon variants of a common disease. int j dermatol. 2016;55(2):e79-82. doi:10.1111/ijd.12927 skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 166 brief article herpes zoster in a 2-year-old child after a single dose of varicella vaccine hope barone do, mph1, mary veremis-ley2, stuart gildenberg, md1,2 1department of dermatology, st. joseph mercy hospital, ann arbor, mi 2midwest center for dermatology, warren, mi the varicella-zoster virus (vzv) is known to cause two forms of infection: primary varicella, characterized by widespread crops of pruritic vesicles and pustules in different stages of development on the trunk and extremities and herpes zoster (hz), characterized by a unilateral dermatomal vesicular eruption after reactivation of latent virus in dorsal root ganglia with subsequent dermal spread via peripheral nerve pathways.1, 2 while the majority of cases are mild and self-limiting, severe complications such as secondary bacterial skin infections, meningoencephalitis, and pneumonia may occur in infants, adults, and immunocompromised persons.1, 2 nationwide adoption of childhood vaccination against the varicella-zoster virus (vzv), which began as a single dose program with live attenuated virus in 1995, has dramatically reduced disease burden and contributed to a 93% decreased varicella associated mortality between 19942006.1 although rare, at 15-93 per 100,000 person-years, the incidence of breakthrough varicella (defined as infection with wild-type varicella >42 days after vaccination) and post-vaccination hz in children led to the implementation of a two-dose series in 2006.3 further evaluation revealed that only 50% of breakthrough varicella or postvaccination hz are attributable to wild-type vzv, with the oka vaccine-strain virus identified in the remaining cases.4 furthermore only 1% of pediatric hz cases were identified in immunocompetent children.5 we report an unusual case of an immunocompetent 2-year-old child who developed herpes zoster in the same dermatomal distribution as the vaccination site received eight months prior. a 32-month-old immunocompetent girl presented with a three-day history of pruritic eruption involving the trunk. the eruption abstract in this report, we describe a rare case of an immunocompetent 2-year-old child who developed herpes zoster (hz) in the same dermatomal distribution as the vaccination site received several months prior. although most cases of hz caused by the vaccine-strain virus follow a mild disease course, affected patients are contagious to household members and may nevertheless develop severe complications such as herpes ophthalmicus and meningoencephalitis. consideration of this entity and associated complications is critical for dermatologists when evaluating similar appearing eruptions. introduction case presentation skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 167 figure 1. multiple vesicles on an erythematous base as well as erythematous papules coalescing into plaques along a dermatomal distribution on the (a) left labia majora (b) left lower abdomen and left anterior proximal thigh, and (c) left upper buttock and lower back. first appeared on the left lower abdomen and left hip and subsequently spread to involve the left labia, thigh, and lower back. the patient’s mother denied the presence of any systemic symptoms such as fever, cough, rhinorrhea, or diarrhea. her first dose of varicella vaccine was administered to the left thigh at 14-months of age. there was no known exposure to chicken pox. another child in the patient’s daycare recently tested positive for sars-cov-2, however all household members including the patient tested negative twice for the virus. physical examination revealed multiple vesicles on an erythematous base as well as erythematous papules coalescing into plaques along a dermatomal distribution on the left lower abdomen, left labia majora, left anterior proximal thigh, left upper buttock, and left lower back. differential diagnosis included herpes zoster, rhus dermatitis, skin manifestations of sars-cov2 infection, impetigo, and gianotti crosti syndrome. polymerase chain reaction (pcr) of fluid obtained from a de-roofed vesicle on the left buttock returned positive for varicella zoster virus. the patient was initiated on acyclovir 200 mg/5 ml oral suspension, 2.5ml three times daily for seven days. she was also started on topical fluticasone propionate 0.05% cream twice daily. in this report, we describe the rare occurrence of immunocompetent childhood herpes zoster following a single dose of varicella vaccine occurring in the same dermatomal pattern as the vaccine injection site. the characteristics of this case are largely congruent with recent literature. the largest study to date of childhood postdiscussion skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 168 vaccination hz since implementation of the two-dose series by weinmann et al (2013) revealed 83 cases, 50% of whom tested positive for the oka vaccine strain at a median age of 2 years.6 the time to onset of eruption following vaccination ranged from 3 months to 11 years.6 new lesions stopped appearing within one week in 79% of cases with complete scabbing taking greater than one week in 71% of cases.6 all patients who tested positive for the vaccine strain were immunocompetent.6 furthermore, up to 92% of hz in 1-2-year-old patients were caused by the oka vaccine-strain.2, 6 similar to the established pathophysiology of hz in adult patients, the proposed mechanism of hz in children is related to the reactivation of the live attenuated virus from dorsal root ganglia followed by viral axonal transport along peripheral nerve pathways to the skin.2 the resultant cutaneous eruption of vaccine-strain hz greatly favors lumbar or cervical dermatomes and corresponds with the most common injection sites of the thigh or upper arm, as in this case.5, 6 this contrasts to wild-type hz eruptions, which most commonly present along thoracic dermatomes.5, 6 although the course of postvaccination hz is generally considered milder than unvaccinated cases, the occurrence of severe complications including meningoencephalitis and hz ophthalmicus are well documented.2, 4 these complications may precede or occur simultaneously to the rash and suggest a possible post-vaccination viremia or spread of the virus along posterior nerve roots to infect the meninges and brain.2, 4 possibly attributable to the lack of reported cases, it remains uncertain whether such severe complications may occur following rash abatement. as with other strains of vzv, children with vaccine-strain hz are considered contagious from the time of skin eruption until all lesions crust over. transmission of the oka strain from immunocompetent children with hz to other adults or children is rare, but may occur within households.1 this is consistent with other findings that one-dose vaccinated individuals are roughly half as contagious when compared to unvaccinated hz cases.1 in general, prognosis is excellent and patients may be treated with acyclovir to prevent scarring or when disease is extensive.5 given the vast majority of reported childhood vzv cases have presented in those deemed immunocompetent, the occurrence of childhood post-vaccination hz is generally not considered an indication for workup of underlying immunodeficiency.7 although our patient did not undergo viral genotyping, positivity for the oka vaccinestrain is highly likely given the lack of known vzv exposure, unique lumbar distribution in the same dermatome as vaccine injection, and known predominance of the vaccinestrain in 1-2-year old patients with hz.2, 6 this diagnosis was further supported by twice negative sars-cov2 testing, which may also present with a papulovesicular varicella-like exanthem, and lack of contact with irritant or allergic substances.8 despite the generally favorable prognosis, increased awareness among pediatricians and dermatologists for post-vaccination hz is warranted to differentiate from mimickers such as sars-cov2 infection and initiate appropriate treatment and precautions. longitudinal follow-up of these patients is warranted to assess the incidence of hz as adults and development of post-vaccination infection after receiving other live-attenuated viruses. conflict of interest disclosures: none funding: none skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 169 corresponding author: hope barone do, mph st. joseph mercy health system dermatology clinic reichart health center 5333 mcauley drive, suite r-5003 ypsilanti, mi, usa 48197 phone: 401-787-4251 email: barone.hope@gmail.com references: 1. centers for disease control and prevention (cdc. prevention of varicella. mmwr. 2007;56:1-40. 2. peterson n, goodman s, peterson m, peterson w. herpes zoster in children. cutis. 2016;98(2):94-5. 3. dagrosa at, collins lk, chapman ms. atypical herpes zoster presentation in a healthy vaccinated pediatric patient. cutis. 2017;100(5):303-4. 4. guffey dj, koch sb, bomar l, huang ww. herpes zoster following varicella vaccination in children. cutis. 2017;99(3):207-11. 5. dreyer s, hemarajata p, hogeling m, henderson gp. pediatric vaccine‐strain herpes zoster: a case series. pediatric dermatology. 2017;34(6):665-7. 6. weinmann s, chun c, schmid ds, roberts m, vandermeer m, riedlinger l, bialek sr, marin m. incidence and clinical characteristics of herpes zoster among children in the varicella vaccine era, 2005-2009. j infect dis. 2013;208:18591868. 7. civen r, chaves ss, jumaan a, jumaan a, wu h, mascola l, gargiullo p, seward j. the incidence and clinical characteristics of herpes zoster among children and adolescents after implementation of varicella vaccination. pediatr infect dis j. 2009;28:954-959. 8. marzano av, genovese g, fabbrocini g, pigatto p, monfrecola g, piraccini bm, veraldi s, rubegni p, cusini m, caputo v, rongioletti f. varicella-like exanthem as a specific covid-19– associated skin manifestation: multicenter case series of 22 patients. j am acad dermatol. 2020. mailto:barone.hope@gmail.com internal use leon kircik, md1; todd schlesinger, md2; april armstrong, md3; brian berman, md, phd4; neal bhatia, md5; james del rosso, do6; mark lebwohl, md1; vishal a. patel, md7; darrell rigel, md, ms1; siva narayanan, phd8; volker koscielny, md9 ismail kasujee phd9 1mount sinai icahn school of medicine, new york, ny, usa; 2clinical research center of the carolinas, charleston, sc, usa; 3keck school of medicine, university of southern california, los angeles, ca, usa; 4university of miami miller school of medicine, miami, fl, usa; 5therapeutics clinical research, san diego, ca, usa; 6jdr dermatology research/thomas dermatology, las vegas, nv, usa; 7george washington school of medicine and health sciences, washington, dc, usa; 8avant health llc, bethesda, md, usa; 9almirall sa, barcelona, spain. impact of actinic keratosis (ak), as measured by patient-reported ak symptoms, and impact on emotions and functioning (using skindex-16) among patients with ak administered tirbanibulin in real-world community practices across the u.s. (proak study) introduction: actinic keratosis (ak) has been shown to negatively affect emotional functioning and skin-related quality of life of patients1. impact of tirbanibulin treatment on the quality of life of patients with aks is not adequately understood. the primary objective of the study was to evaluate patient-reported outcomes in terms of ak symptoms, and impact of aks on emotions and functioning, among ak patients treated with tirbanibulin in community practices across the u.s. methods: a single-arm, prospective cohort study (proak) was conducted among adult patients with ak of the face or scalp who were newly initiated with tirbanibulin treatment in real-world practices in the u.s, as part of usual care. patients and clinicians completed surveys and clinical assessments at baseline, week-8 (timeframe for main endpoints) and week-24. skindex-16, completed at baseline and week-8, is a 16-item survey with 3 domains: symptoms (4 items), emotions (7 items) and functioning (5 items), with each domain score computed on a scale of 0 to 100 with higher score indicating severe impairment due to aks. changes from baseline in skindex-16 scores were analyzed, as observed. results: a total of 290 patients with aks completed the study assessments at week-8. patient self-reported skin-texture at baseline was – dry: 39.66%, smooth: 47.59%, rough: 19.66%, bumpy: 18.62%, scaly: 35.17%, blistering/ peeling: 6.55%. baseline skindex-16 domain scores were: symptoms: 22.30, emotions: 38.17, functioning: 14.41. at week-8, a statistically significant (p<0.0001) decrease in scores from baseline was observed for all skindex-16 domains, with week-8 domain scores being symptoms: 8.15, emotions: 13.49, functioning: 4.63. conclusion: patients with aks who used oncedaily tirbanibulin treatment for 5-days reported a significant reduction in the symptoms and emotional/functional impact domains of skindex-16, at week-8. reference: 1. br j dermatol. 2013;168(2):277-283. synopsis conclusions • within the study cohort of adult patients with aks administered once-daily tirbanibulin treatment for 5-days as part of usual care, a significant reduction in ak burden was observed, as indicated by the improvement in ak symptoms and emotional/functional impact (using skindex-16), at week-8. • the demonstrated effectiveness and the safe and tolerable profile of once-daily tirbanibulin treatment highlights the benefits associated with this novel therapeutic option in routine community practice settings, for optimal management of aks. sponsored by almirall, s.a. methods • a single-arm, prospective cohort study (proak) was conducted among adult patients with aks on the face or scalp who were newly initiated with once-daily tirbanibulin treatment (5-day course) in real-world community practices in the u.s, as part of usual care. • a total of 300 subjects were enrolled from 32 community practices across the u.s. • patients and clinicians completed surveys and clinical assessments at baseline, week-8 (timeframe for main endpoints) and week-24, concerning safety and effectiveness of tirbanibulin. • skindex-16, a validated pro instrument, was completed by patients at baseline and week-8. • this 16-item survey has 3 domains, namely, symptom domain (4 items), emotions domain (7 items) and functioning domain (5 items). • all items are scored on a seven-point adjectival response scale, with a potential score of 0 (never bothered) to 6 (always bothered). • each domain score is individually computed on a scale of 0 to 100 with higher score indicating severe impairment due to aks. • changes from baseline in skindex-16 domain scores at week-8 were analyzed, as observed. objective • the primary objective of the study was to evaluate patient-reported outcomes in terms of ak symptoms, and impact of aks on emotions and functioning, among ak patients treated with tirbanibulin in community practices across the u.s. results • proak study (nct05260073) was initiated in 2022, with more than 75% of the study patients treated with tirbanibulin between april and august of 2022. • out of 300 enrolled patients, a total of 290 patients with aks completed the study assessments at week-8, and hence included in the analyses. • overall, in 77.93% and 33.79% of study patients (not mutually exclusive), ak lesions on their face and scalp respectively were treated with tirbanibulin. • all patients (100%) completed their 5-day once-daily treatment course. • ten patients were not included in the week-8 analyses: 1 patient had missing data, and 9 patients were discontinued from the study due to patient voluntary withdrawal of consent or lost to follow-up. • no discontinuations were related to adverse drug reactions (adrs), and there were no serious adrs reported at week-8. table 1: baseline patient characteristics n=290 age, mean years [min, max] 66.30 [30.00, 90.00] gender, % female male 31.38 68.62 primary health insurance, % private insurance medicaid medicare uninsured 41.72 3.10 53.79 1.38 history of skin cancer, % 61.72 fitzpatrick skin type, % type i type ii type iii type iv type v 7.59 71.38 18.62 1.38 1.03 baseline patient selfreported skin-texture, % dry smooth rough bumpy scaly blistering peeling 39.66 47.59 19.66 18.62 35.17 0.34 6.21 baseline severity of skin photodamage in ak affected area, % absent mild moderate severe 1.03 21.38 56.55 20.34 22.30 38.17 14.41 8.15 13.49 4.63 0.00 10.00 20.00 30.00 40.00 50.00 symptom emotions functioning s ki nd ex d om ai n m ea n s co re baseline week 8 figure 1: mean skindex-16 domain scores significantly decreased over the 8-week study observation period cfb: 14.26* cfb: 24.88* cfb: 9.78* n= 290; one & four patients had missing data at baseline for symptom & emotions domain respectively; one patient had missing data at week-8 for emotions domain. cfb: change from baseline to week-12. *p <0.0001 table 2: site characteristics (n=32) current workplace: private, office-based practice, % 100 total number of board-certified dermatologists in the clinic/practice, mean 3.53 number of patients with aks managed by the clinic in a given month, mean 136.34 number of years practicing dermatology, mean 15.66 poster presented at 13th annual winter clinical dermatology conference | maui, hi | january 12 17, 2018 burden of axillary hyperhidrosis using a patient-reported outcome measure to assess impact on activities and bothersomeness david m. pariser,1 adelaide a. hebert,2 janice drew,3 john quiring,4 dee anna glaser5 1eastern virginia medical school and virginial clinical research, inc., norfolk, va; 2uthealth mcgovern medical school at houston, houston, tx; 3dermira, inc., menlo park, ca; 4qst consultations, allendale, mi; 5saint louis university, st. louis, mo introduction • hyperhidrosis, which is estimated to affect 4.8% of the us population or approximately 15.3 million people, is associated with considerable impairment in work productivity, social activities, emotional well-being, and personal relationships1,2 • glycopyrronium tosylate (gt; formerly drm04), a topical cholinergic receptor antagonist, has been assessed in 2 replicate randomized phase 3 clinical trials (atmos-1 and atmos-2) for the treatment of primary axillary hyperhidrosis in patients ≥9 years of age; the primary efficacy and safety results of these studies have been previously reported3 • patient-reported outcomes (pros) in these trials were assessed using recently developed axillary hyperhidrosis patient measures (ahpm) which includes three separate assessments: the 4-item axillary sweating daily diary (asdd; patients <16 years of age completed a modified, child-specific 2-item version [asdd-c]), 6 weekly impact items, and a single-item patient global impression of change (pgic)3,4 – asdd/asdd-c axillary sweating severity item (item 2) has been specifically developed and validated to support regulatory approval3 objective • to evaluate the burden of disease associated with primary axillary hyperhidrosis utilizing pro measures reported at baseline for patients who participated in atmos-1 and atmos-2 methods atmos-1 and atmos-2 study design • atmos-1 (nct02530281; sites in the us and germany) and atmos-2 (nct02530294; us sites only) were parallel-group, 4-week, double-blind, phase 3 clinical trials in which patients with primary axillary hyperhidrosis were randomized (2:1) to gt or vehicle (figure 1) • for the purposes of this analysis, data from the gt and vehicle groups from each study have been pooled • eligible patients were ≥9 years of age and had primary axillary hyperhidrosis for ≥6 months, gravimetricallymeasured sweat production of ≥50 mg/5 min in each axilla, asdd axillary sweating severity item (item 2) score ≥4, and hyperhidrosis disease severity scale (hdss) grade ≥3 • patients were excluded for history of a condition that could cause secondary hyperhidrosis; prior surgical procedure or treatment with a medical device for axillary hyperhidrosis; treatment with iontophoresis within 4 weeks or treatment with botulinum toxin within 1 year for axillary hyperhidrosis; axillary use of nonprescription antiperspirant within 1 week or prescription antiperspirant within 2 weeks; new or modified psychotherapeutic medication regimen within 2 weeks; and/or treatment with medications having systemic anticholinergic activity, centrally acting alpha-2 adrenergic agonists, or beta-blockers within 4 weeks unless dose had been stable ≥4 months and was not expected to change; figure 1. study design week 0 week 4 atmos-1 and atmos-2 target recruitment: 330 patients randomized in each study 2:1 gt vehicle gt, glycopyrronium tosylate burden of disease measures • ahpm (table 1) – the asdd consists of 4 items and was used for patients ≥16 years; patients <16 years of age completed a modified, child-specific, 2-item version called the asdd-c (table 1) – patients ≥16 years were additionally asked to complete 6 weekly impact items and a single-item pgic (table 1) • the burden of disease associated with primary axillary hyperhidrosis was summarized by descriptive statistics in the intent-to-treat (itt) population (all randomized subjects who were dispensed study drug) based on: – mean score at baseline on asdd axillary sweating severity item (item 2; all patients) and items addressing the impact and bother of sweating (items 3 and 4, respectively; patients ≥16 years of age); baseline was defined as the average of ≥4 days of data in the most recent 7 days prior to randomization – mean score at baseline for weekly impact items (patients ≥16 years of age); baseline was defined as the last available record prior to day 1 • an additional analysis was performed to assess the proportion of patients with moderate-to-severe axillary sweating, impact, and bother, defined as scores of 9 or 10 on asdd item 2 and scores of 3 or 4 on asdd items 3 and 4, respectively table 1. axillary hyperhidrosis patient measures (ahpm)a axillary sweating daily diary (asdd)b instructions: the questions in the diary are designed to measure the severity and impact of any underarm sweating you have experienced within the previous 24 hour period, including nighttime hours. while you may also experience sweating in other locations on your body, please be sure to think only about your underarm sweating when answering these questions. please complete the diary each evening before you go to sleep. item 1 [gatekeeper] during the past 24 hours, did you have any underarm sweating? yes/no when item 1 is answered “no,” item 2 is skipped and scored as zero item 2 during the past 24 hours, how would you rate your underarm sweating at its worst?0 (no sweating at all) to 10 (worst possible sweating) item 3 during the past 24 hours, to what extent did your underarm sweating impact your activities?0 (not at all), 1 (a little bit), 2 (a moderate amount), 3 (a great deal), 4 (an extreme amount) item 4 during the past 24 hours, how bothered were you by your underarm sweating? 0 (not at all bothered), 1 (a little bothered), 2 (moderately bothered), 3 (very bothered), 4 (extremely bothered) axillary sweating daily diary-children (asdd-c)c instructions: these questions measure how bad your underarm sweating was last night and today. please think only about your underarm sweating when answering these questions. please complete these questions each night before you go to sleep. item 1 [gatekeeper] thinking about last night and today, did you have any underarm sweating? yes/no when item 1 is answered “no,” item 2 is skipped and scored as zero item 2 thinking about last night and today, how bad was your underarm sweating? 0 (no sweating at all) to 10 (worst possible sweating) weekly impact itemsb instructions: please respond “yes” or “no” to each of the following questions. a. during the past 7 days, did you ever have to change your shirt during the day because of your underarm sweating? yes/no b. during the past 7 days, did you ever have to take more than 1 shower or bath a day because of your underarm sweating? yes/no c. during the past 7 days, did you ever feel less confident in yourself because of your underarm sweating? yes/no d. during the past 7 days, did you ever feel embarrassed by your underarm sweating? yes/no e. during the past 7 days, did you ever avoid interactions with other people because of your underarm sweating? yes/no f. during the past 7 days, did your underarm sweating ever keep you from doing an activity you wanted or needed to do? yes/no patient global impression of change (pgic) itemb overall, how would you rate your underarm sweating now as compared to before starting the study treatment? 1 (much better), 2 (moderately better), 3 (a little better), 4 (no difference), 5 (a little worse), 6 (moderately worse), 7 (much worse) aasdd/asdd-c item 2 is a validated pro measure bfor use in patients ≥16 years of age cfor use in patients ≥9 to < 16 years of age results • a total of 697 patients were randomized and were asked to complete asdd/asdd-c items 1 and 2; 665 patients were ≥16 years of age and were asked to complete items addressing the impact and bother of sweating (items 3 and 4, respectively), and the weekly impact items • demographics and baseline disease characteristics were similar between studies (table 2) table 2. baseline demographic and disease characteristics (itt populations) atmos-1 (n=344) atmos-2 (n=353) demographics age (years), mean ± sd 32.7 ± 11.9 32.6 ±11.0 age group, n (%) <16 years ≥16 years 11 ( 3.2) 333 (96.8) 21 ( 5.9) 332 (94.1) male, n (%) 154 (44.8) 172 (48.7) white, n (%) 276 (80.2) 294 (83.3) bmi (kg/m2), mean ± sd 27.5 ± 5.5 27.7 ± 5.2 baseline disease characteristics years with primary axillary hyperhidrosis, mean ± sd 14.5 ± 10.7 16.5 ±10.7 sweat production (mg/5 min)a, mean ± sd 178.7 ± 237.4 168.9 ± 153.2 hdssb, n (%) grade 3 grade 4 217 (63.1) 127 (36.9) 215 (60.9) 137 (38.8) asdd/asdd-c item 2c, mean ± sd 7.2 ± 1.7 7.3 ± 1.6 agravimetrically measured bhdss grade 3 or 4 was an inclusion criteria for the study; 1 subject entered atmos-2 with hdss=2, which was a protocol violation caverage of daily records from the 7 days prior to date of first dose; a minimum of 4 days was required to compute the average asdd, axillary sweating daily diary; asdd-c; asdd-children; bmi, body mass index; hdss, hyperhidrosis disease severity score; itt, intent-to-treat; sd, standard deviation • at baseline in atmos-1 and atmos-2, the mean ± sd asdd/asdd-c axillary sweating severity item (item 2) scores were 7.2 ± 1.7 and 7.3 ± 1.6, respectively – in each trial, more than half of all patients reported weekly average scores ≥7 before randomization, indicating that patients considered their sweating to be moderate or severe at baseline (figure 2) – 16.0% and 19.3% of patients rated the severity of their axillary sweating as 9 or 10 in atmos-1 and atmos-2, respectively, indicating severe axillary hyperhidrosis at baseline (figure 2) figure 2. proportion of patients reporting moderate-to-severe axillary sweating at baseline (asdd/asdd-c item 2 scores) 59.3% 59.8% average score ≥7 16.0% 19.3% average score 9 or 10 atmos-1 (n=344) atmos-2 (n=353) 80 100 60 40 20 0 b as el in e a s d d it em 2 s co re s, % o f p at ie nt s data are representative of the intent-to-treat (itt) population asdd item 2: during the past 24 hours, how would you rate your underarm sweating at its worst? 0 (no sweating at all) to 10 (worst possible sweating) asdd-c item 2: thinking about last night and today, how bad was your underarm sweating? 0 (no sweating at all) to 10 (worst possible sweating) asdd, axillary sweating daily diary; asdd-c, asdd-children • at baseline in atmos-1 and atmos-2, mean ± sd asdd item 3 (impact of axillary sweating) scores were 2.3 ± 0.9 and 2.4 ± 0.9, respectively – in each trial, approximately 70% of patients ≥16 years of age reported scores ≥2 on asdd item 3, indicating that their daily activities were at least moderately affected by axillary hyperhidrosis at baseline (figure 3) – 26.2% and 29.7% of patients were severely impacted by axillary sweating in atmos-1 and atmos-2, respectively, having reported scores of 3 or 4 at baseline (figure 3) figure 3. proportion of patients reporting moderate-to-severe impact of axillary sweating at baseline (asdd item 3 scores) 69.4% 71.7% average score ≥2 26.2% 29.7% average score 3 or 4 atmos-1 (n=344) atmos-2 (n=353) 80 100 60 40 20 0 b as el in e a s d d it em 3 s co re s, % o f p at ie nt s data are representative of the intent-to-treat (itt) population asdd item 3: during the past 24 hours, to what extent did your underarm sweating impact your activities? 0 (not at all), 1 (a little bit), 2 (a moderate amount), 3 (a great deal), 4 (an extreme amount) asdd, axillary sweating daily diary • at baseline in atmos-1 and atmos-2, the mean ± sd asdd item 4 (bother of axillary sweating) scores were 2.6 ± 0.9 and 2.6 ± 0.9, respectively – in each trial, >75% of patients ≥16 years of age reported scores ≥2 on asdd item 4, indicating that they were at least moderately bothered by axillary sweating at baseline (figure 4) – 37.5% and 40.1% of patients were severely bothered by axillary sweating in atmos-1 and atmos-2, respectively, having reported scores of 3 or 4 at baseline (figure 4) figure 4. proportion of patients reporting moderate-to-severe bother of axillary sweating at baseline (asdd item 4 scores) 77.8% 77.4% average score ≥2 37.5% 40.1% average score 3 or 4 atmos-1 (n=344) atmos-2 (n=353) 80 100 60 40 20 0 b as el in e a s d d it em 4 s co re s, % o f p at ie nt s data are representative of the intent-to-treat (itt) population asdd item 4: during the past 24 hours, how bothered were you by your underarm sweating? 0 (not at all bothered), 1 (a little bothered), 2 (moderately bothered), 3 (very bothered), 4 (extremely bothered) asdd, axillary sweating daily diary • at baseline, the majority of patients who were ≥16 years of age answered ‘yes’ to questions asking if their underarm sweating affected their actions or emotions (weekly impact items) during the past week (figure 5) – notably, more than 96% of patients reported feeling embarrassed figure 5. proportion of patients answering ‘yes’ to weekly impact items 83.9% 87.3% a. needed to change shirt during the day 60.4% 54.0% b. needed ≥1 shower/bath a day 89.5% 93.0% c. felt less confident 96.7% 96.3% d. felt embarrassed 68.1% 65.0% e. avoided interactions 58.2% 58.3% f. kept from doing an activity atmos-1 (n=304) atmos-2 (n=300) 80 100 60 40 20 0 % o f p at ie nt s an sw er in g “y es ” to w ee kl y im pa ct it em s data are representative of the intent-to-treat (itt) population conclusions • at baseline, more than half of all patients who participated in atmos-1 and atmos-2 reported that their sweating was at least a 7 on an 11-point scale where 0 represents no sweating and 10 represents worst possible sweating • in patients who were ≥16 years of age, axillary hyperhidrosis at least moderately affected their daily activities and was considered at least moderately bothersome – approximately 1 in 5 patients reported experiencing severe axillary sweating – approximately 1 in 3 reported feeling severely impacted and/or bothered by their sweating • on a weekly basis, the majority of patients who were ≥16 years of age reported being markedly impacted by their excess sweating, with most having to avoid interactions or take additional measures (ie, showering/bathing more than once a day; changing shirts during the day) to manage their excessive sweating; more than 90% of patients were less confident or embarrassed by sweating • these findings are consistent with previous reports that hyperhidrosis is associated with a substantial disease burden; as such, safe and effective new treatment options are needed for this disease references 1. doolittle et al. arch dermatol res. 2016; 308 (10):743-9. 2. hamm. dermatology. 2006;212:343-53. 3. pariser et al. poster presented at: 13th annual maui derm for dermatologists; 2017; maui, hi. 4. nelson et al. development and validation of the axillary sweating daily diary: a patient-reported outcome measure to assess sweating severity. br j dermatol. [submitted] acknowledgements the authors would like to thank sheri fehnel, dana dibenedetti, and lauren nelson, from rti health solutions, as well as diane ingolia and christine conroy, from dermira, inc., for their work developing the pro questionnaire. these studies were funded by dermira, inc. medical writing support was provided by prescott medical communications group. all costs associated with development of this abstract were funded by dermira, inc. author disclosures dmp: consultant and investigator for dermira, inc.; ah: consultant for dermira, inc.; employee of the university of texas medical school, houston, which received compensation from dermira, inc. for study participation; jd: employee of dermira, inc; jq: employee of qst consultations; dag: consultant and investigator for dermira, inc. skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 147 brief article a case of linagliptin-induced bullous pemphigoid brenda carrillo, bs1, natalya m. gallaga, bs1, paige hoyer, md2, lindy ross, md2, michael wilkerson, md2 1university of texas medical branch school of medicine, galveston, tx 2univeristy of texas medical branch, department of dermatology, galveston, tx bullous pemphigoid (bp) is an autoimmune disease characterized by subepidermal blisters and autoantibodies against hemidesmosomal proteins of the basement membrane, bp 180 and bp 230.1 it predominantly affects the elderly and typically presents as tense vesicles and bullae in normal-appearing skin or over erythematous or urticarial plaques.1 the bullae later rupture and cause pruritic erosions.1 bp can also have atypical variants such as eczematous or urticarial lesions, excoriations from pruritus, or solely pruritus without rash.1 drugs such as furosemide, spironolactone, ibuprofen, topical diclofenac, amoxicillin, ciprofloxacin, ace inhibitors, tnf-alpha inhibitors, and potassium iodide, among many others, have been implicated in drug-induced bp.1 recently, dipeptidyl peptidase-4 (dpp-4) inhibitors have been increasingly associated with bp. 2-8 dpp-4 inhibitors are a relatively newer drug class used to treat diabetes mellitus, with the first one, sitagliptin, being approved by the fda in 2006.2 while the mechanism by which they may induce bp is not entirely clear, an association between these has become evident.3,8 a 73-year-old woman with a history of diabetes mellitus ii and hypertension presented for evaluation of intermittent blisters. she reported the lesions appeared mostly on her scalp, mouth, upper chest, arms, and, occasionally, on her legs (figure 1). the lesions were associated with a abstract bullous pemphigoid is an autoimmune subepidermal blistering condition in which autoantibodies target components of the hemidesmosomal proteins. it typically presents as pruritic bullous lesions in a generalized distribution. certain drugs such as diuretics, nsaids, antibiotics, and ace inhibitors have been implicated in the development of bullous pemphigoid. recently, a class of medications for type ii diabetes, dipeptidyl peptidase-4 (dpp-4) inhibitors (commonly called gliptins) have been implicated in drug-induced bullous pemphigoid. we report a case of a 73-year-old female with type ii diabetes mellitus who presented with biopsy-proven bullous pemphigoid after being treated with linagliptin. after discontinuing linagliptin and receiving first-line treatment, the patient achieved remission by her five-week follow-up. it is imperative that dermatologists and primary care physicians remain aware of this association when diagnosing and treating bullous pemphigoid, particularly in diabetic patients. introduction case presentation https://www.zotero.org/google-docs/?3lnpao https://www.zotero.org/google-docs/?kfsyhs https://www.zotero.org/google-docs/?x6805b https://www.zotero.org/google-docs/?jo1kuz https://www.zotero.org/google-docs/?jdhuxy skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 148 figure 1. erythematous erosions on (a) arm, (b) dorsal hand and (c) upper back “burning” sensation and she experienced pruritus when they “popped”. her current medications at the time of onset included atorvastatin, carvedilol, insulin detemir, levothyroxine, linagliptin, ramipril, terazosin, aspirin, cholecalciferol, coenzyme q10, docosahexanoic acid/epa, magnesium, milk thistle, vitamin b complex and vitamin k2. a skin biopsy showed subepidermal bullae with eosinophils consistent with bullous pemphigoid. direct immunofluorescence showed moderate linear igg and c3 at the basement membrane. drug-induced bullous pemphigoid associated with either linagliptin or ramipril was suspected. because linagliptin was the most recent drug added to her regimen of the two, it was discontinued and ramipril was continued. the patient was instructed to apply clobetasol 0.05% cream twice a day to affected areas of the body and 0.05% fluocinonide gel twice a day to mucosal lesions. she had full resolution of her lesions and pruritus at her five-week follow-up, with no recurrence. had the lesions not resolved past four months, after allowing sufficient time for igg antibodies to decay, then discontinuation of the ace inhibitor would have been attempted. the patient’s remission after discontinuing linagliptin while still on an ace inhibitor, another drug commonly known to induce bp, suggests this case was likely induced by linagliptin. cases of gliptin-induced bullous pemphigoid have been reported in various case reports as well as in nationwide studies. a european pharmacosurveillance study showed disproportionate incidence for bullous pemphigoid and vildagliptin, linagliptin, saxagliptin, and sitagliptin.3 this study used proportional reporting ratios (prr) as a measure of disproportionality and found bp was reported relatively more frequently with these agents than with other drugs. similarly, a japanese pharmacosurveillance study showed disproportionate incidence between bp and vildagliptin, teneligliptin, and linagliptin in a disproportionality analysis using reporting odds ratios (ror).4 in addition, an israeli discussion a. b. c. skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 149 table 1. dpp4-inhibitor withdrawal and first-line treatment in gliptin-induced bp benzaken et al. 2018 magdaleno tapial et al. 2020 kridin and bergman 2018 plaquevent et al. 2019 patient demographics male/female 17/11 19/12 21/15 58/50 age, years <80: n = 14 >80: n = 14 77.71 ± 8.4 (sd) 0-69: n = 10 70-79: n = 10 >80: n = 16 77.9 ± 9.3 (sd) dpp4-i involved (n) vildagliptin (14) sitagliptin (10) linagliptin (3) saxagliptin (1) vildagliptin (12) sitagliptin (5) linagliptin (13) saxagliptin (1) vildagliptin (24) sitagliptin (6) linagliptin (9) - vildagliptin (59) sitagliptin (44) - saxagliptin (5) treatment high-potency topical steroids, systemic corticosteroids if refractory, followed by taper corticosteroids po prednisone >1mg/kg (n = 22), adjuvant immunosuppressant (n=15), topical steroid (n = 4) high potency topical corticosteroid, systemic corticosteroid #bp patients discontinued dpp4-i 19/28 27/31 19/36 48/106 dpp4-i discontinuation results complete (11/19) or partial (7/19) remission complete response (26/27), 1 death complete remission off therapy (6/19), minimal therapy (9/19), partial remission (3/19). 1 death median 15 days to control disease. first relapse in 17/39 patients with delay of 4.8 months. 15-day delay of disease control dpp4-i continuation results 1 complete remission. 4 partial remission. 1 relapse. 3 deaths. 3/4 partial remission (1 lost to follow-up) complete remission off therapy (3/13), minimal therapy (4/13), 8 deaths median 14 days to control disease. first relapse in 13/35 patients with delay of 5.8 months. 14-day delay of disease control study conclusions dpp4-i withdrawal (and initiation of first line treatment) had favorable impact dpp4-i withdrawal combined with firstline treatment results in complete clinical response in almost all patients dpp4-i withdrawal lead to improved clinical course no statistical significance in delay of disease control (p = 0.95), rate (p=0.63), delay of relapse (p=0.9) dpp4-i dipeptidyl peptidase-4 inhibitor; bp – bullous pemphigoid, sd – standard deviation; po – per oral case-controlled cohort study found linagliptin to be significantly associated with bp, although to a lower extent than vildagliptin.5 gliptins, including linagliptin, have been implicated in several individual case reports as well. latency times have ranged from a few months to more than a year.2 therefore, it is important to consider the possibility of linagliptin-induced bullous pemphigoid even when the patient has been on a gliptin for several years. furthermore, our patient was in remission after administration of first-line treatment and removal of the gliptin. this is consistent with several other studies. benzaken et al. found that 95% of cases achieved remission when the gliptin was removed and first-line treatment was provided.6 magdaleno-tapial et al. found that 96% of patients in which the agent was skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 150 withdrawn were in remission.7 one study found that patients in which the agent was removed had a better clinical course that those who continued on the dpp-4 inhibitors.5 however, one study found that there was no difference in median time to achieve disease control, rate, or relapse between groups who stopped or continued gliptin use when both groups were treated with corticosteroids.8 because of differences in treatment between the patients in these studies, it is difficult to assess the effectiveness of agent withdrawal alone on patient prognosis. nevertheless, changing the patient to a different medication may still be worth considering. despite the increasing reports of gliptininduced bullous pemphigoid, the exact mechanism is still not clear. dpp-4 inhibitors increase glucagon-like peptide-1 and glucose-dependent insulin-trophic polypeptide, leading to increased insulin release and decreased glucagon secretion.2 dpp-4 is expressed in many different cells of the body, including the skin.5 it is a plasminogen receptor which can activate plasminogen leading to the activation of plasmin,9 which is known to cleave bp180.10 inhibition of dpp-4 may lead to improper cleavage of bp180, possibly changing its capacity to induce an immune response.11 inhibition of dpp-4 may also increase the activity of chemokines, induce eosinophil activation, and subsequently lead to tissue damage.12 due to the increasing number of reported cases of gliptin-induced bp, it is important for physicians to be aware of this association and consider it when encountering a patient with type ii diabetes mellitus and bullous pemphigoid. knowledge of this association can help in assessing patients and considering withdrawal of the gliptin as part of the treatment plan. however, it may be reasonable to attempt treatment of bp with topical steroids prior to discontinuing the gliptin if deemed necessary by the primary care physician. conflict of interest disclosures: none funding: none corresponding author: brenda carrillo, bs department of dermatology university of texas medical branch 301 university blvd. 4.112, mccullough building galveston, tx, 77550 phone: 409-772-3376 email: brecarri@utmb.edu references: 1. bolognia jl, ed. dermatology: expertconsult. 3rd edition ff. elsevier; 2012. accessed june 1, 2020. https://www.clinicalkey.com/#!/browse/book/3s2.0-c20131144449 2. someili a, azzam k, hilal ma. linagliptinassociated alopecia and bullous pemphigoid. eur j case rep intern med. 2019;6(9):001207001207. 3. garcía m, aranburu ma, palacios-zabalza i, lertxundi u, aguirre c. dipeptidyl peptidase-iv inhibitors induced bullous pemphigoid: a case report and analysis of cases reported in the european pharmacovigilance database. j clin pharm ther. 2016;41(3):368-370. 4. arai m, shirakawa j, konishi h, sagawa n, terauchi y. bullous pemphigoid and dipeptidyl peptidase 4 inhibitors: a disproportionality analysis based on the japanese adverse drug event report database. diabetes care. 2018;41(9):e130-e132. 5. kridin k, bergman r. association of bullous pemphigoid with dipeptidyl-peptidase 4 inhibitors in patients with diabetes: estimating the risk of the new agents and characterizing the patients. jama dermatol. 2018;154(10):1152. 6. benzaquen m, borradori l, berbis p, et al. dipeptidyl peptidase iv inhibitors, a risk factor for bullous pemphigoid: retrospective multicenter conclusion skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 151 case-control study from france and switzerland. j am acad dermatol. 2018;78(6):1090-1096. 7. magdaleno-tapial j, valenzuela-oñate c, esteban hurtado á, et al. association between bullous pemphigoid and dipeptidyl peptidase 4 inhibitors: a retrospective cohort study. actas dermo-sifiliográficas engl ed. 2020;111(3):249253. 8. plaquevent m, tétart f, fardet l, et al. higher frequency of dipeptidyl peptidase-4 inhibitor intake in bullous pemphigoid patients than in the french general population. j invest dermatol. 2019;139(4):835-841. 9. gonzalez-gronow m, kaczowka s, gawdi g, pizzo sv. dipeptidyl peptidase iv (dpp iv/cd26) is a cell-surface plasminogen receptor. front biosci j virtual libr. 2008;13:1610-1618. 10. hofmann sc, voith u, schönau v, sorokin l, bruckner-tuderman l, franzke c-w. plasmin plays a role in the in vitro generation of the linear iga dermatosis antigen ladb97. j invest dermatol. 2009;129(7):1730-1739. 11. izumi k, nishie w, mai y, et al. autoantibody profile differentiates between inflammatory and noninflammatory bullous pemphigoid. j invest dermatol. 2016;136(11):2201-2210. 12. forssmann u, stoetzer c, stephan m, et al. inhibition of cd26/dipeptidyl peptidase iv enhances ccl11/eotaxin-mediated recruitment of eosinophils in vivo. j immunol. 2008;181(2):1120-1127. skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 345 compelling comments the history of cosmetic nail treatments, from babylon to beyoncé jeanette r. zambito ba, msa auniversity of rochester medical center, rochester, ny cosmetic nail treatment refers to the stylization, embellishment, or enhancement of one’s natural fingernails or toenails. while often seen as a leisure activity, these treatments can pose significant dermatologic health risks including traumatic onycholysis, mycobacterial infections, and contact dermatitis1. modern enhancements such as the gel manicure, ultraviolet treated nails, and acrylic nails each come with their own host of dermatologic complications. nonetheless, the demand for these nail beautification services has continually grown into what is now a multibillion-dollar business in the united states.1 this large, dynamic, and fascinating industry had humble beginnings dating back thousands of years. around 3500 bc, babylonian male warriors adorned their nails with ground minerals as part of a pre-battle ritual designed to intimidate their enemies. the ancient egyptians used henna to dye the nails a redbrown color while the ancient greeks preferred a mixture of yellow flower petals, pollen, and potassium salt to color the nails a pale flaxen color. around 3000 bc, china elevated nail art by using a crude form of nail lacquer composed of beeswax and egg whites. by 1000 bc, gold and silver were the preferred nail colors, a trend that recently came back into fashion after beyoncé was spotted wearing gold minx nail foils. the chinese even enhanced their nails with gemstones, demonstrating that the intrigue of bedazzling predates the modern era.2 it wasn’t until the 1920s, when the automobile industry developed new paints, that the modern-day manicure was born.3 in 1937, the creator of tupperware (earl tupper), invented glue-on appliques. less than 20 years later, a dentist named fred slack tried to fix a broken fingernail with acrylic leading to the unintentional invention of acrylic nails.4 from there, it was only a matter of time before we were left with the sculpted, studded, pierced, and stenciled nails of today. conflict of interest disclosures: none. funding: none. corresponding author: jeanette zambito, ba, ms university of rochester medical center rochester, mn jeanette_zambito@urmc.rochester.edu references: 1. rieder ea, tosti a. cosmetically induced disorders of the nail with update on contemporary nail manicures. j clin aesthet dermatol. 2016;9(4):39-44. mailto:jeanette_zambito@urmc.rochester.edu skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 346 2. schafer l. nail care: from ancient rites to new heights. nails magazine. sep 1993. 3. pagano, f.c. a review of nail polish: the industrial cosmetic. cosmetics and toiletries. 2011, 126, 372–380 4. a history of nails. nails magazine. sep 2012. powerpoint presentation figure 1: ibm watson explorys universe demographics poster presented at the 2017 amcp nexus meeting in dallas, tx; october 16-19, 2017. the psoriasis patient journey: progression from topical to biologic treatment for psoriasis patients in the united states jashin j wu1; minyi lu2; karen a veverka2; maartje smulders3; eros papademetriou3; yunjua junhua3; steven r feldman4 1department of dermatology, kaiser permanente los angeles medical center, los angeles, ca, usa; 2leo pharma inc., madison, nj, usa; 3smartanalyst, nyc, new york, usa; 4department of dermatology, wake forest university school of medicine, north carolina, usa objective results conclusions methods acknowledgements references this study aims to describe the patient treatment journey of pso-diagnosed patients who initially receive a topical prescription and then receive a biologic treatment during follow-up. retrospective observational cohort study database: ibm watson explorys (figure 1)  electronic health records (ehr) database made up from 39 integrated delivery networks (idns) across us and comprised of approximately 55 million patients patient inclusion  index topical date: initial topical prescription b/w jan 1, 2011 and june 30, 2015  adult patients: ≥ 18 years at index topical date  pso diagnosis: icd-9 cm diagnosis code 696.1 or icd-10 cm diagnosis codes (l40.0, l40.8, l40.9) between 6 months prior to or 2 months post index topical date  patients had either ≥ 2 pso diagnoses made by any physician or 1 pso diagnosis made by a dermatologist. patients were required to not have a topical prescription 6 months prior to the index topical date. patients were also required to have activity in the ehr for at least 12 months prior to the index topical date and at least 36 months after the index topical date. outcomes were assessed in a 36-month follow-up period. patient exclusion  patients who received an oral or biologic agent prescription in the 12 months prior to the index topical date.  patients who had a confounding dermatological or non-dermatological condition (where a tnf inhibitor is indicated) that was diagnosed during or before the pso diagnosis date. prescription drugs classes included for analyses  topical steroids: grouped into class 1-2 or 3-7 steroids  oral agents: cyclosporine, methotrexate, acitretin, hydroxyurea, leflunomide, apremilast, azatioprine, dexamethasone, isoretinoin, methoxsalen, methylprednisolone, prednisone, tacrolimus, and sulfasalazine  biologic agents: etanercept, adalimumab, ustekinumab, infliximab, and secukinumab statistical analyses  between-group patient characteristics were compared using analysis of variance for continuous variables and chi-square tests for categorical variables without adjustment. multivariable cox regression analysis was used to assess whether the difference between time to biologic was significantly different between patients who directly switched to or added on a biologic versus patients who initially received an oral agent prescription followed by a biologic prescription duration of treatment use definitions  for all drug types, no distinction was made between a patient switching medication(s) or adding on medication(s).  topical drugs: each new and refill prescription for a topical drug was assumed to be used for 30 days. a gap of 45 days or longer was assumed to be a stop or pause in topical treatment  oral agents: the duration of use was calculated by dividing the total quantity of tablets prescribed by the tablets administered per day, based on dosing instructions. when one of these fields was not available for a given prescription, we substituted the calculated median duration from prescriptions where it was available for each drug  biologics: the duration of use was calculated by multiplying the recommended maintenance dosing schedule for each medication by the number of syringes dispensed. since infliximab is given intravenously, we assumed a duration of 56 days for each treatment as per the recommended maintenance dosing schedule table 1. patient cohort demographic patient cohort  there were 33,397,271 adult patients aged ≥ 18 years in the explorys database between january 1, 2011 and june 30, 2015, of whom 143,133 (0.4 %) had at least one pso diagnosis.  of these patients, 38,390 had either ≥2 pso diagnoses by any physician type or 1 pso diagnosis made by a dermatology specialist and no confounding conditions before pso diagnosis.  within this cohort, 24,481 patients received a topical prescription and 22,484 were defined as being topical treatment-naive. of these patients, 6729 had a psoriasis diagnosis and started topical treatment, met all the study inclusion criteria and were included in the analysis. (table 1) demographics  mean age of patients at time of switch to or add on of a biologic (48 years, sd 13.3) was significantly lower than mean age (54.5 years, sd 15.4) of patients at first topical treatment who never received a biologic in the 36-month follow-up period (p<0.001) (table 1) duration of topical use  within the total patient cohort, 1712 (25.4%) stopped topical treatment in the 36-month follow-up period. the remaining 5017 (74.6%) patients continued, or stopped and then restarted, topical treatment in the 36-month follow-up period.  the median cumulative duration of any topical use was approximately 365 days (iqr: 233-558 days) (table 2)  approximately 1 in 10 people starting topical treatment for psoriasis switch from topical to biologics over a 3-year period.  the time to initiating the biologic after topical treatment is longer for patients who initially switched to an oral psoriasis treatment followed by a biologic treatment.  maintaining patients on an effective topical treatment may help minimize the need for a switch to biologics limitations:  the results of this study were derived from a large retrospective ehr database which primarily covers provider administrative data, including written prescriptions. however, no medication dispensing data is included. therefore, these results mainly describe provider prescribing behavior, rather than actual medication use, which could be used by the patient, and could be slightly different.  it is important to note that yearly psoriasis prevalence among eligible patients in the database varied from 0.4-0.5%, which is a rather small prevalence.  it is possible that some patients with a biologic do not receive a topical treatment first; these patients would been excluded by our methodology.  as the database grows, more patient behavior related results can be presented. drug total patients n (%) steroids 1-2 (± another drug) 270 (63.7%) steroids 3-7 (± another drug) 176 (41.5%) betamethasone and calcipotriene (± another drug) 65 (15.3%) vitamin d (± another drug) 51 (12.0%) * p<0.001 table 3a. topical agents prescribed prior to biologic switch or add-on (n = 424) patients were most frequently (63.74%) prescribed a class 1-2 steroid prior to biologic start (table 3a) 1. smith j, cline a, feldman sr. advances in psoriasis. south med j. 2017 jan;110(1):65-75. 2. menter a, gottlieb a, feldman sr, van voorhees as, leonardi cl, gordon kb, et al. guidelinesof care for the management of psoriasis and psoriatic arthritis: section 1. overview of psoriasisand guidelines of care for the treatment of psoriasis with biologics. j am acad dermatol2008;58(5):826-50. this study was based in part on ehr data from the explorys, an ibm watson database, conducted by smartanalyst, and sponsored by leo pharma. editorial support was provided by dharm patel, phd at leo pharma inc., us. patient population (n=6,729) patients with biologic during 36month follow-up: no (n = 5988) yes (n=741) female sex, n (%) 53.8% 53.5% 56.4% mean age, years (sd)* 53.8 (15.3) 54.5 (15.4) 48 (13.3) median age, years (iqr) 55(43,65) 56(44,66) 48 (39,58) ethnicity african-american, n (%) 288 (4.3%) 246 (4.1%) 42 (5.7%) asian, n (%) 59 (0.9%) 53 (0.9%) 6 (0.8%) caucasian, n (%) 5890 (87.5%) 5257 (87.8%) 633 (85.4%) hispanic/latino, n (%) 48 (0.7%) 37 (0.6%) 11 (1.5%) multi-racial, n (%) 36 (0.5%) 32 (0.5%) 4 (0.5%) other, n (%) 224 (3.3%) 193 (3.2%) 31 (4.2%) missing, n (%) 184 (2.7%) 170 (2.8%) 14 (1.9%) region east, n (%) 925 (13.7%) 848 (14.2%) 77 (10.4%) midwest, n (%) 3669 (54.5%) 3304 (55.2%) 365 (49.3%) south, n (%) 1342 (19.9%) 1099 (18.4%) 243 (32.8%) west, n (%) 550 (8.2%) 502 (8.4%) 48 (6.5%) missing, n (%) 243 (3.6%) 235 (3.9%) 8 (1.1%) index topical agent for patients who continued topical treatment in the 36-month follow-up period (n=5017) estimated median cumulative duration during 36-month follow-up period days (iqr) steroid class 1-2 392.5 (247-572.5) steroid class 3-7 368 (246-571) vitamin d 437.5 (301-633.5) calcipotriol / betamethasone 401 (261-591) nsaid 360 (270-590.5) vitamin a 396 (253-586) anthralin 310 (240-582) steroid 1-2 392.5 (247-572.5) table 2. estimated median cumulative duration of topical use by class (n = 5017) time to switch to/add-on of biologic  the median time from topical start date to biologic start date was significantly greater for patients (n=317) who initially received an oral agent prescription followed by a biologic prescription (488 days; iqr: 238 797 days), compared to patients (n=424) who directly switched from/added a topical to a biologic (206 days; iqr: 71.5 – 523 days) (p<0.0001). (figure 2) o patient groups were controlled for age, gender and ethnicity patient cohort treatment patterns  during the 36-month follow up period, 317 (42.7%) patients received an oral agent prescription initially, followed by a biologic prescription; while 424 (57.3%) patients directly switched to or added on a biologic prescription.  of this second group, 160 (37.7%) subsequently received an oral agent prescription after the biologic. (figure 3)  of the patients who directly switched to or added a biologic prescription first (n = 741), adalimumab was the most common treatment (n = 349 [74.1%]). (figure 4) figure 2: time from index topical to initiation of biologic figure 4: biologics prescribed first within patient cohort (n = 741) figure 3: patient cohort treatment patterns agent total patients n (%) methotrextate 164 (51.7%) all_prednisone 117 (36.9%) dexamethasone 37 (11.7%) acitretin 28 (8.8%) sulfasalazine 17 (5.4%) cyclosporine 15 (4.7%) apremilast 14 (4.4%) leflunomide 5 (1.6%) hydroxyurea 2 (0.6%) methoxsalen 2 (0.6%) isotretinoin 1 (0.3%) methylprednisolone 1 (0.3%) tacrolimus 1 (0.3%) oral agents were prescribed directly before the switch to/add on of a biologic for a total of 317 patients and the top two were methotrexate (51.7%) and prednisone (36.9%) (table 3b) the median cumulative duration of use of specific oral agents prescribed before a biologic prescription was 123 days for methotrexate (iqr: 56-229), and 28 days for prednisone (iqr: 14-58). table 3b. topical agents prescribed prior to biologic switch or add-on (n = 424) slide number 1 results: pharmacokinetic tomography of a single daily dose of bpx-01 this work was sponsored by biopharmx; all investigators were active participants in the trial. bpx-01 is limited by federal or us law to investigational use only. introduction 1wellman center for photomedicine, massachusetts general hospital, harvard medical school, boston, massachusetts 02114, usa 2biopharmx, inc, menlo park, california 94025, usa 3harvard-mit division of health sciences and technology, cambridge, massachusetts 02139, usa methods to limit systemic exposure to antibiotic, and to achieve localized delivery into the skin, a topical minocycline (bpx-01) is being developed clinically to address acne vulgaris by targeting the lesions directly. knowing the efficiency of topical delivery could translate to a better understanding of clinically effective dose. we have previously demonstrated transepidermal and transfollicular penetration of minocycline with conventional fluorescence microscopy. however, because of poor signal-to-noise (snr) due to high endogenous tissue fluorescence, this technique required ‘infinite’ dosing. recently, we have demonstrated the use of two-photon excitation fluorescence (2pef) microscopy in identifying minocycline with the equivalent of about 2.5 daily doses. in the current study, we introduced a novel method of visualization and quantification of minocycline within human skin tissue by utilizing a phasor approach to fluorescence lifetime microscopy (flim) to further enhance the snr. fresh frozen human facial skin specimens undergoing only a single freeze-thaw cycle were used in the study. skin specimens were dosed with 2.5 mg/cm2, equivalent to a single daily dose, at 1% and 2% bpx-01 for 24 hours, and then cut to 30-mm sections. femtosecond laser pulses from an optical parametric oscillator (opo) tuned to 780 nm were used to generate two-photon excited fluorescence signals from the tissue sections. signals were acquired with photomultiplier tubes (pmt) to reconstruct flim images. in phasor analysis of flim, the fluorescence decay trace from each pixel in the flim image is plotted as a single point in the phasor plot. since every fluorophore has a specific decay trace, we can identify a specific molecule by its position in the phasor plot. the unique signature of minocycline in flim phasor analysis was successfully differentiated from the endogenous fluorescence of human tissue. based on our preliminary analysis, we believe that the visualization and quantification method using a phasor approach to flim can play an important role in future pharmacokinetics (pk) and pharmacodynamics (pd) analyses. 1. m. a. digman, v. r. caiolfa, m. zamai, e. gratton, “the phasor approach to fluorescence lifetime imaging analysis,” biophys j: biophys lett., l14-16, 2007 2. lakner, p.h., monaghan, m.g., moller, y., olayioye, m.a. & schenke-layland, k. “applying phasor approach analysis of multiphoton flim measurements to probe the metabolic activity of three-dimensional in vitro cell culture models”, sci. rep. 7, 42730 (2017). 3. m. hermsmeier, t. sawant, d. lac, a. yamamoto, x. chen, u. nagavarapu, c. l. evans; k. f. chan, “visualizing and quantifying drug distribution in tissue,” proc. spie vol:10046, 100460a (2017); doi: 10.1117/12.2256621 sinyoung jeong1, maiko hermsmeier2, sam osseiran1,3, akira yamamoto2, usha nagavarapu2, kin f. chan2, conor l. evans1 visualization of cutaneous distribution of minocycline of a topical gel in human facial skin with two-photon excited fluorescence lifetime imaging microscopy (flim) and phasor analysis ep id er m is h a ir f o ll ic le se ba ce o u s g la n d figure 1. experimental setup for fluorescence lifetime imaging microscopy (flim). 780-nm femtosecond laser pulses were delivered to the sample; two-photon excitation fluorescence was filtered with a 680-nm short-pass and a 620-nm bandpass filters, with the time-resolved signal captured by a photomultiplier tube and time-correlated with the flim reference. from the two signals the fluorescence lifetime, t, (inset) specific for minocycline or endogenous fluorophores may be determined. ex vivo human facial skin specimens were obtained and stored at -80 c frozen condition. prior to experimentation, the specimens were let to thaw. each donor specimen was divided into blank (negative) control, vehicle control, 1% bpx-01 and 2% bpx-01 treatment arms. for the vehicle, 1% and 2% bpx-01 arms, the specimens were treated with 2.5 mg/cm2 of the topical gel. all four arms were maintained at 32 c for the dosing period of 24 hours. post treatment the tissues were embedded in oct, cut to 30-mm thick sections, and mounted onto microscope slides. the samples were then placed onto a flim setup as shown in figure 1. femtosecond laser pulses at 780 nm were delivered to each sample for twophoton excitation, and time-resolved fluorescence signals were acquired by a photomultiplier tube (pmt) along with the excitation source reference signal. t pmt 620/60 filter sample 680 short-pass filter flim-620 channel flim-reference 780 nm femtosecond laser pulse 485 nm long-pass dichroic filter o 𝐼= 𝐼𝑜𝑀𝑒 − 𝑡t𝑀 + 𝐼𝑜𝑠𝑒 − 𝑡t𝑠 𝐼= 𝐼𝑜𝑠𝑒 − 𝑡t𝑠 i i t t time domain signals 3. each frequency domain datapoint is rearranged as a scatter plot in the polar coordinate separating the minocycline fluorescence from that of skin autofluorescence minocycline fluorescence skin autofluorescence frequency domain (phasor plot) qm qs o minocycline uptake images raw fluorescence image 1. each pixel on the image has a specific fluorescence lifetime corresponding to fluorophore species 2. each time-domain fluorescence lifetime signal is converted to frequency domain having amplitude and phase information 4. the minocycline uptake in human tissue is remapped with false color (red color in fig. 3) by sorting the pixels associated with the cluster of minocycline signature in the phasor plot. figure 2. flim analysis with phasor plot and image overlay the fluorescence signals were timecorrelated to the flim reference, and in phasor analysis the time-domain fluorescence signals were converted to frequency-domain using fourier transform. the resulting amplitude and phase information from this operation allowed the dataset to be rearranged in a scatter plot (phasor plot) in polar coordinate as shown in figure 2.1,2 such approach accentuated the signals originating from an exogenous fluorophore such as minocycline because of its distinct fluorescence lifetime from that of endogenous tissue fluorophores, which was generally absent in the blank and vehicle groups. false colors were then assigned to differentiate minocycline (red color in right column of figure 3) from endogenous fluorescence and re-mapped to produce the flim images. poster presented at the 2017 fall clinical dermatology conference®; las vegas, nv; october 12-15, 2017. bright field 2pef images (590-650 nm) flim images phasor plots minocycline uptake images blank vehicle 1% bpx-01 2% bpx-01 blank vehicle 1% bpx-01 2% bpx-01 blank vehicle 1% bpx-01 2% bpx-01 references in conclusion, with flim analysis, tissue samples treated with a single daily dose of both 1% and 2% bpx-01 exhibited substantial uptake in the epidermis and the hair follicle. trace amount of minocycline was also found in the sebaceous gland where it would have otherwise been difficult to identify with 2pef microscopy. quantitative estimation of minocycline local concentrations appeared viable with flim-phasor analysis. this is the first such study designed to demonstrate the potential of flim-phasor analysis in understanding the absorption and distribution of a drug substance, minocycline, as part of a translational research program. the flim experimental setup enabled co-registration of a series of images acquired in the bright field and 2pef, as shown in figure 3. previously, our team have shown that the 2pef approach alone was adequate in demonstrating minocycline uptake and distribution in an ex vivo human facial skin model with approximately 2.5x daily dose or higher of bpx-01 at 4 hrs and 24 hrs.3 in the current study, only a single daily dose of bpx-01 was applied. as a result, we found it difficult to determine among the 2pef images if minocycline fluorescence was present when compared to the blanks (negative controls) and the vehicle controls, as endogenous tissue fluorescence appeared to be overwhelming any fluorescence from the drug substance. however, with the phasor approach to time-correlated single photon counting fluorescence lifetime microscopy (flim), we revealed the presence of minocycline distribution within all anatomical structures of interest in the skin – the epidermis, hair follicle and sebaceous gland – in both the 1% and 2% bpx-01 treatment groups. we observed a general trend among the flim images in which minocycline distribution was most concentrated in the epidermis, followed by the hair follicle, and with noticeable trace amount in the sebaceous gland, in a single daily dose treatment after 24 hrs of incubation time. these observations were supported by the amount of identifiable data points associated with minocycline fluorescence among the corresponding phasor plots from different areas of the skin. the phasor approach also enabled quantification of local concentrations of minocycline as shown in the far right column in figure 3. figure 3. flim analysis starting (from left to right column) bright field images, two-photon excitation fluorescence (2pef) images, flim images, phasor plots corresponding to flim images, and quantitative analysis of local minocycline concentration, in the epidermis, hair follicle and sebaceous gland by phasor analysis. fc17posterbiopharmxjeongvisualizationofcutaneousdistribution.pdf acknowledgements: medical writing support was provided by prescott medical communications group (chicago, il) with financial support from ortho dermatologics; ortho dermatologics is a division of bausch health us, llc | 2020 fall clinical dermatology conference® for pas & nps • april 3-5, 2020 • orlando, fl synopsis ◾ acne is a prevalent disease, occurring in 85% of adolescents1 ◾ prevalence in adults is increasing and it occurs more often in females than males2,3 ◾ in addition, older age and female sex are associated with a greater impact on quality of life (qol)4 ◾ the first lotion formulation of tretinoin 0.05%, developed by utilizing novel polymeric emulsion technology, was efficacious and well tolerated in two phase 3 studies of patients ≥9 years of age with moderate-to-severe acne (nct02932306, nct02965456)5 objective ◾ to assess efficacy and safety of tretinoin 0.05% lotion in females of various age groups with moderate-to-severe acne methods ◾ in two phase 3 double-blind, randomized, multicenter, parallel-group, vehicle-controlled studies, patients ≥9 years of age with moderate-to-severe acne were randomized (1:1) to tretinoin 0.05% lotion or vehicle once daily for 12 weeks • in this study, cerave® hydrating cleanser and cerave® moisturizing lotion (l’oreal, ny) were provided as needed for optimal moisturization/cleaning of the skin ◾ data from these 2 studies were pooled and analyzed post hoc in a subset of female patients by age: 13-19 years, 20-29 years; and 30+ years ◾ efficacy assessments included reductions in inflammatory and noninflammatory lesions, percentage of patients achieving ≥2-grade reduction in evaluator’s global severity scores (egss), and acne-specific quality of life questionnaire (acne-qol) ◾ cutaneous safety and tolerability were also evaluated results participants ◾ the pooled population included 865 female patients • 13-19 years (tretinoin, n=173; vehicle, n=184) • 20-29 years (tretinoin, n=163; vehicle, n=189) • 30+ years (tretinoin, n=80; vehicle, n=76) ◾ the majority of patients in each age group had an egss score of 3 (moderate) at baseline (13-19 y, 93.3%; 20-29 y, 88.9%; 30+ y, 95.5%) efficacy within age groups (treatment versus vehicle) ◾ at week 12, least-squares mean percent reductions from baseline in inflammatory and noninflammatory lesion counts were significant versus vehicle in the tretinoin-treated 13-19 year group; in the tretinoin-treated older age groups, reductions from baseline versus vehicle were only significant for noninflammatory lesions, which may be due to the limited number of patients in each group (figure 1) ◾ the percentage of patients achieving ≥2-grade egss reduction in each age group was greater with tretinoin treatment versus vehicle, though differences were not significant (figure 2) tretinoin 0.05% lotion for the once-daily treatment of moderate-to-severe acne vulgaris in females: effect of age on efficacy and tolerability figure 2. percentage of participants achieving ≥2-grade reduction in evaluator global severity scores by age group and visit (itt population, pooled) #( 0% 10% 20% 30% 1.6% week 4 p e rc e n ta g e o f p a rt ic ip a n ts 5.2% 4.3% 2.0% 5.8% 4.6%vehicle: 5.7% week 8 7.6% 12.8% 6.5% 15.2% 10.5% #( 24.4% week 12 17.0% 25.9% 16.8% 30.7% 18.8% 40% 13-19 y (n=173) 20-29 y (n=163) 30+ y (n=80) there were no significant differences across the 3 age groups at weeks 4, 8, or 12. vehicle: 13-19 y (n=184); 20-29 y (n=189); 30+ y (n=76). multiple imputation method used for missing values. itt, intent-to-treat; ls, least squares. figure 3. mean change from baseline at week 12 in quality of life by age group (itt population, pooled) 0 2 4 6 7.5 selfperception m e a n c h a n g e f ro m b a se lin e 7.0 10.2 8.8 8.8 9.5vehicle: 14 13-19 y (n=173) 20-29 y (n=163) 30+ y (n=80) 8 10 12 im p ro ve m e n t 6.7 roleemotional 6.1 10.0 7.9 7.5 8.6 4.5 rolesocial 3.8 6.5 6.5 6.4 7.2 5.2 acne symptoms 5.1 9.1 7.4 8.1 7.6 **p≤0.01 vs vehicle. there were no significant differences across the 3 age groups at weeks 4, 8, or 12. vehicle: 13-19 y (n=184); 20-29 y (n=189); 30+ y (n=76). higher scores for each domain reflect improved health-related qol. no imputation for missing values. itt, intent-to-treat; qol, quality of life. safety ◾ in the tretinoin-treated group, mean cutaneous safety and tolerability ratings were all between none (0) or mild (1) within each age group at weeks 4, 8, and 12 ◾ by week 12, any mild, transient increases in cutaneous safety and tolerability in each age group had returned to baseline values or improved (figure 4) ◾ age-related trends were observed with hyperpigmentation, in which older females had higher mean baseline values; however, mean ratings were still below mild (1) at baseline and did not increase by week 12 figure 4. mean cutaneous safety and tolerability scores in tretinoin-treated females by age group and visit (safety population, pooled) 0 1 scaling m e a n s co re severe3 age 13-19 at baseline age 13-19 at week 12 2 erythema itching burning moderate mild stinging hypopigmentation hyperpigmentation age 20-29 at baseline age 20-29 at week 12 age 30+ at baseline age 30+ at week 12 no imputation for missing values. scores were rated from 0 (none) to 3 (severe). conclusions ◾ in adult and adolescent females with moderate-to-severe acne, tretinoin 0.05% lotion was effective versus vehicle in reducing noninflammatory lesions at week 12; in addition, tretinoin lotion significantly reduced inflammatory lesions in adolescents at week 12 ◾ reductions in acne lesions/egss scores and improvements in qol domains were generally greater in the older age groups (20-29 and 30+ years) compared with younger females (13-19 years), although these differences did not reach statistical significance ◾ tretinoin 0.05% lotion was well tolerated by all age groups references 1. zaenglein al, et al. j am acad dermatol. 2016;74(5):945-973.e933. 2. skroza n, et al. j clin aesthet dermatol. 2018;11(1):21-25. 3. collier cn, et al. j am acad dermatol. 2008;58(1):56-59. 4. tan jk, et al. j cutan med surg. 2008;12(5):235-242. 5. tyring sk, et al. j drugs dermatol. 2018;17(10):1084-1091. author disclosures linda stein gold has served as investigator/consultant or speaker for ortho dermatologics, leo, dermavant, incyte, novartis, abbvie, and lilly. david m pariser has served as consultant to atacama therapeutics, bickel biotechnology, biofrontera ag, celgene, dermira, leo, regeneron, sanofi, tdm surgitech, theravida, and ortho dermatologics; investigator for abbott laboratories, almirall, amgen, aobiome, asana biosciences, bickel biotechnology, celgene, dermavant, dermira, eli lilly, leo, menlo therapeutics, merck & co., novartis, novo nordisk a/s, ortho dermatologics, pfizer, regeneron, and stiefel; on advisory board for pfizer; and on the data monitoring board for bms. marci levy has nothing to disclose. eric guenin is an employee of ortho dermatologics and may hold stock and/or stock options in its parent company. ◾ qol improvements at week 12 were significant versus vehicle in the tretinoin-treated 20-29 group for self-perception, role-emotional, and acne symptoms (figure 3) across age groups ◾ reductions in inflammatory or noninflammatory lesion counts and the percent of participants with ≥2-grade egss reduction were generally greater in the 20-29 and 30+ age groups compared with the 13-19 age group, although these differences were not statistically significant (figures 1 and 2) ◾ the greatest improvements in qol domains occurred in the 20-29 and 30+ groups compared with the 13-19 group; these differences did not reach statistical significance (figure 3) figure 1. ls mean percent reduction from baseline in inflammatory and noninflammatory lesion counts by age group and visit (itt population, pooled) #( -70% -50% -30% -10% -30.5% week 4 ls m e a n p e rc e n t c h a n g e f ro m b a se lin e a. in�ammatory lesions -27.4% -28.1% -24.1% -34.6% -36.3%vehicle: -44.6% week 8 -37.9% -46.7% -36.4% -50.3% -49.7% #( -55.3% week 12 -45.2% -55.8% -46.6% -63.5% -56.7% 13-19 y (n=173) 20-29 y (n=163) 30+ y (n=80) #( -70% -50% -30% -10% -21.3% week 4 ls m e a n p e rc e n t c h a n g e f ro m b a se lin e b. nonin�ammatory lesions -17.0% -25.6% -18.2% -27.6% -20.3%vehicle: -36.0% week 8 -22.1% -39.2% -29.9% -45.2% -36.4% #( -47.1% week 12 -27.6% -55.2% -39.3% -59.0% -45.4% 13-19 y (n=173) 20-29 y (n=163) 30+ y (n=80) 0% 0% *p<0.05 vs vehicle; **p<0.01 vs vehicle; ***p<0.001 vs vehicle. there were no significant differences across the 3 age groups at weeks 4, 8, or 12. vehicle: 13-19 y (n=184); 20-29 y (n=189); 30+ y (n=76). multiple imputation method used for missing values. itt, intent-to-treat; ls, least squares. linda stein gold, md1; david m pariser, md2; marci levy, pa-c3; eric guenin, pharmd, phd, mph4 1henry ford hospital, detroit, mi; 2virginia clinical research center, norfolk, va; 3gold skin care center, nashville, tn; 4ortho dermatologics*, bridgewater, nj *ortho dermatologics is a division of bausch health us, llc. abstract • introduction: secukinumab, a fully human anti-interleukin-17a monoclonal antibody, has previously demonstrated superior efficacy to ustekinumab in the phase 3b clear study of moderate to severe plaque psoriasis.1,2 here, we report 16-week results from clarity, the second head-to-head trial comparing secukinumab with ustekinumab. • methods: in this ongoing multicenter, head-to-head, double-blind, parallel-group, phase 3b study (nct02826603), patients were randomized 1:1 to receive subcutaneous secukinumab 300 mg or ustekinumab per label. the co-primary objectives are to demonstrate the superiority of secukinumab over ustekinumab at week 12 in relation to the proportion of patients with (1) 90% or more improvement from baseline psoriasis area and severity index (pasi 90) and (2) a score of 0/1 (clear/almost clear) on the investigator’s global assessment (iga mod 2011 0/1). key secondary objectives include demonstrating the superiority of secukinumab over ustekinumab with respect to pasi 75 at week 4; pasi 75 and 100 at week 12; pasi 75, 90, 100; and iga mod 2011 0/1 at week 16. missing values were handled by multiple imputation. • results: at week 12, both co-primary objectives were met, secukinumab 300 mg (n = 550) was significantly superior to ustekinumab (n = 552) for the proportion of patients achieving both pasi 90 (66.5% vs. 47.9%; p < 0.0001) and iga mod 2011 0/1 (72.3% vs 55.4%; p < 0.0001) response rates. additionally, all key secondary objectives were met. at week 4, pasi 75 response rates were significantly superior with secukinumab 300 mg compared to ustekinumab (40.2% vs 16.3%; p < 0.0001). at week 16, secukinumab 300 mg demonstrated significantly superior response rates compared to ustekinumab for pasi 75 (91.7% vs 79.8%; p < 0.0001), pasi 90 (76.6% vs 54.2%; p < 0.0001), pasi 100 (45.3% vs 26.7%; p < 0.0001), and iga mod 2011 0/1 (78.6% vs 59.1%; p < 0.0001). furthermore, at week 12, patients receiving secukinumab 300 mg compared to ustekinumab had significantly greater pasi 75 (88.0% vs 74.2%; p < 0.0001) and pasi 100 (38.1% vs 20.1%; p < 0.0001) responses. safety findings were consistent with the known safety profile of secukinumab. • conclusions: secukinumab demonstrated superior results with greater improvements compared to ustekinumab across all study outcomes at week 4, 12, and 16 in patients with moderate to severe plaque psoriasis. introduction • secukinumab, a fully human monoclonal antibody that inhibits interleukin (il)-17a, has been shown to have significant efficacy in the treatment of moderate to severe psoriasis and psoriatic arthritis, demonstrating sustained high levels of efficacy with a favorable safety profile3–5 – secukinumab has also shown efficacy in dedicated trials of scalp, nail, and palmoplantar psoriasis6–8 – additionally, secukinumab has previously demonstrated superior efficacy to ustekinumab in the phase 3b clear study of moderate to severe plaque psoriasis1 • here, we report 16-week results from clarity, the second head-tohead trial comparing secukinumab with ustekinumab methods • clarity (nct02826603) is a multicenter, double-blinded, parallelgroup, phase 3b study • patients were required to have moderate to severe psoriasis at baseline defined as: – psoriasis area and severity index (pasi) score of ≥12 and – body surface area (bsa) affected by plaque-type psoriasis ≥10% and – investigator’s global assessment, 2011 modification (iga mod 2011) ≥3 (based on a scale of 0–4) • patients were randomized 1:1 to subcutaneous secukinumab 300 mg at baseline, weeks 1, 2, and 3, and then every 4 weeks from week 4 to 48 or subcutaneous ustekinumab (45 mg for patient weighing ≤100 kg or 90 mg for patient weighing >100 kg) at baseline, week 4, and then every 12 weeks (figure 1) • coprimary objectives of the study are to demonstrate the superiority of secukinumab compared to ustekinumab with respect to: – pasi 90 at week 12 – iga mod 2011 0/1 (clear or almost clear skin) at week 12 • key secondary objectives will be assessed sequentially by a hierarchical testing strategy, and include measures testing the superiority of secukinumab compared to ustekinumab with respect to the following (shown in hierarchical order): 1. pasi 75 at week 12 2. pasi 75 at week 4 3. pasi 90 at week 16 4. pasi 100 at week 16 5. iga mod 2011 0/1 at week 16 6. pasi 100 at week 12 7. pasi 75 at week 16 • missing values were handled by multiple imputation in this analysis primary efficacy endpoint screening -4 to rand. r an do m iz at io n ustekinumab 45/90 mg1 secukinumab 300 mg bl 1 2 3 4 8 12 16 20 24 28 32 36 40 44 48 52 f4 eot f8 treatment phase follow-up2 1 = ustekinumab dose is based on body weight at baseline; 45 mg for patient ≤ 100 kg; 90 mg for patient > 100 kg 2 = for patients with premature treatment discontinuation only follow-up visit f4 is approximately 4 weeks after the eot visit. follow-up visit f8 is approximately 8 weeks after the eot visit = active dose administration; in order to keep the blind, patients will receive placebo administrations at several time points (not shown in this study design figure) bl, baseline; eot, end of treatment phase figure 1. study design • a total of 1102 patients were randomized: 550 to receive secukinumab 300 mg and 552 to receive ustekinumab (figure 2) – the rate of discontinuation was low and balanced between treatment arms total n = 1102 patients randomized secukinumab 300 mg n = 550 united states 62.7% adverse events (n = 6) other (n = 12) ustekinumab 45/90 mg n = 552 united states 65.6% adverse events (n = 4) other (n = 13) ongoing at week 16 (n = 532) discontinued at week 16 (n = 18) ongoing at week 16 (n = 535) discontinued at week 16 (n = 17) figure 2. patient disposition • demographic and baseline disease characteristics were well balanced across patients receiving secukinumab 300 mg and ustekinumab 45/90 mg (table 1) table 1. patient demographic and baseline disease characteristics parameter secukinumab 300 mg (n = 550) ustekinumab 45/90 mg (n = 552) mean age, years (sd) 45 (14.1) 45 (14.2) sex, male, n (%) 356 (64.7) 376 (68.1) race, white, n (%) 414 (75.3) 410 (74.3) mean weight, kg (sd) > 100 kg, n (%) 91.0 (24.88) 189 (34.4) 93.0 (24.85) 188 (34.1) mean pasi score (sd) score > 20, n (%) 20.8 (8.95) 210 (38.2) 21.3 (9.19) 226 (40.9) bsa affected, % (sd) 29.2 (17.93) 29.5 (17.69) iga mod 2011 score; severe disease, n (%) 209 (38.0) 239 (43.3) mean time since first diagnosis of plaque-type psoriasis, years (sd) 16.8 (11.88) 17.3 (13.34) previous exposure to biologic psoriasis therapy: yes, n (%) 110 (20.0) 130 (23.6) bsa, body surface area, iga mod 2011, investigator’s global assessment, 2011 modification; pasi, psoriasis area and severity index; sd, standard deviation efficacy • both coprimary objectives were met: – secukinumab 300 mg was superior to ustekinumab for the proportion of patients that achieved pasi 90 responses at week 12 (66.5% vs 47.9%; p < 0.0001) – secukinumab 300 mg was also superior to ustekinumab for the proportion of patients that achieved iga mod 2011 0/1 responses at week 12 (72.3% vs 55.4%; p < 0.0001) • secukinumab demonstrated statistical superiority compared with ustekinumab at week 4 and maintained superiority to week 16 (figure 3 a-c) figure 3. iga mod 2011 0/1 (a), pasi 90 (b), and pasi 100 (c) response rates through week 16 • additionally, all key secondary objectives were met in the hierarchical testing strategy (table 2) table 2. hierarchical efficacy analysis of key secondary objectives objectives (shown in order of hierarchical testing strategy) secukinumab 300 mg (n = 550) ustekinumab 45/90 mg (n = 552) p value pasi 75 at week 12 88.0% 74.2% < 0.0001 pasi 75 at week 4 40.2% 16.3% < 0.0001 pasi 90 at week 16 76.6% 54.2% < 0.0001 pasi 100 at week 16 45.3% 26.7% < 0.0001 iga mod 2011 0/1 at week 16 78.6% 59.1% < 0.0001 pasi 100 at week 12 38.1% 20.1% < 0.0001 pasi 75 at week 16 91.7% 79.8% < 0.0001 iga mod 2011 0/1, investigator’s global assessment, 2011 modification, clear (0) or almost clear (1); pasi, psoriasis area and severity index safety • the safety profile of secukinumab was similar to that reported in previous secukinumab clinical trials – to prevent unblinding of treatment groups, detailed safety results are not presented – complete safety data will be presented upon completion of the study conclusions • both coprimary objectives were met with secukinumab demonstrating superiority to ustekinumab for pasi 90 and iga mod 2011 0/1 response rates at week 12 • additionally, secukinumab demonstrated robust superiority with greater improvements compared with ustekinumab across all study objectives up to week 16 • the safety of secukinumab was consistent with the known secukinumab safety profile results *p < 0.0001 iga mod 2011 0/1, investigator’s global assessment, 2011 modification, clear (0) or almost clear (1) score; pasi 90/100, psoriasis area and severity index 90%/100% improvement vs baseline 0 26.9* 72.3* 78.6* 7.8 55.4 59.1 0 20 40 60 80 100 0 4 8 12 16 week iga mod 2011 0/1 a b 0 16.7* 66.5* 76.6* 4.0 47.9 54.2 0 20 40 60 80 100 0 4 8 12 16 week pasi 90 % r es po nd er s % r es po nd er s 0 5.7* 38.1* 45.3* 0.7 20.1 26.7 0 20 40 60 80 100 0 4 8 12 16 % r es po nd er s week pasi 100 c secukinumab 300 mg ustekinumab 45/90 mg secukinumab is superior to ustekinumab in clearing skin of patients with moderate to severe plaque psoriasis: clarity, a randomized, controlled, phase 3b trial jerry bagel1, john nia2, peter hashim2, manmath patekar3, ana de vera3, sophie hugot3, kuan sheng4, summer xia5, elisa muscianisi4, andrew blauvelt6, mark lebwohl2 1psoriasis treatment center of central new jersey, east windsor, nj, usa; 2icahn school of medicine at mount sinai, new york, ny, usa; 3novartis pharma ag, basel, switzerland; 4novartis pharmaceuticals corporation, east hanover, nj, usa; 5novartis beijing novartis pharma co. ltd, shanghai, china; 6oregon medical research center, portland, or, usa references 1. thaçi d, et al. j am acad dermatol. 2015;73(3):400-409. 2. blauvelt a, et al. j am acad dermatol. 2017;76:60-69. 3. bissonnette r, et al. br j dermatol. 2017;177(4):1033-1042. 4. langley rg, et al, for the erasure and fixture study groups. n engl j med. 2014;371(4):326-338. 5. mease pj, et al. n engl j med. 2015;373(14):1329-339. 6. bagel j, et al. j am acad dermatol. 2017;77(4):667-674. 7. reich k, et al. presented at the 8th international psoriasis from gene to clinic congress; 30th november – 2nd december, 2017; london, uk. 8. gottlieb a, et al. j am acad dermatol. 2017;76(1):70-80. disclosures j bagel: investigator and consultant for abbvie, amgen, boehringer-ingelheim, sun, janssen, leo, novartis, celgene, eli lilly; consultant and speaker for valiant; speakers’ bureau for abbvie, eli lilly, janssen, leo, novartis. j nia and p hashim: nothing to disclose. m patekar, a de vera, s hugot: employees of novartis pharma ag. k sheng, e muscianisi: employees of novartis pharmaceuticals corporation. s xia: employee of novartis beijing novartis pharma co. ltd. a blauvelt: scientific adviser and clinical study investigator for abbvie, aclaris, allergan, almirall, amgen, boehringer-ingelheim, celgene, dermavant, dermira, inc., eli lilly, genentech/roche, glaxosmithkline, janssen, leo, meiji, merck sharp & dohme, novartis, pfizer, purdue pharma, regeneron, sandoz, sanofi genzyme, sienna pharmaceuticals, sun pharma, ucb pharma, valeant, vidac; paid speaker for eli lilly, janssen, regeneron, sanofi genzyme. m lebwohl: employee of mount sinai, which receives research funds from amgen, anacor, boehringer–ingelheim, celgene, lilly, janssen biotech, kadmon, leo pharmaceuticals, medimmune, novartis, pfizer, sun pharmaceuticals, and valeant. acknowledgements the authors thank the patients and their families and all investigators and their staff for participation in this study. oxford pharmagenesis, inc., newtown, pa, provided assistance with editing, layout, and printing the poster; this support was funded by novartis pharmaceuticals corporation, east hanover, nj. this research was sponsored by novartis pharma ag, basel, switzerland. the authors had full control of the contents of this poster. poster presented at: 13th annual winter clinical dermatology conference, maui, hi, usa; january 12–17, 2018. download document at the following url: http://novartis.medicalcongressposters.com/default.aspx?doc=e8240 and via text message (sms) text: qe8240 to: 8nova (86682) us only +18324604729 north, central and south americas; caribbean; china +447860024038 uk, europe & russia +46737494608 sweden, europe scan to download a reprint of this poster skin january 2018 volume 2 issue 1 copyright 2018 the national society for cutaneous medicine 64 brief articles clinical experience with a novel topical adhesive for dermatologic excisional wound closure: a case-series ryan m. svoboda md ms a , joshua d. zuckerman md b , darrell s. rigel md ms c a clinical research fellow, national society for cutaneous medicine, new york, ny b zuckerman plastic surgery c clinical professor, department of dermatology, nyu school of medicine, new york, ny in recent years, there has been increased interest in the use of topical tissue adhesives—particularly 2-octyl cyanoacrylate—as an alternative to suture or staple closure of the skin following surgical procedures. 1 while there have been abstract background. the topical adhesive, 2-octyl cyanoacrylate, has been used as an alternative to sutures for closure of skin in a variety of surgical procedures. while potential benefits exist, reports of allergic contact dermatitis and exothermic reactions have been a barrier to widespread adoption by dermatologic surgeons. objective. to describe our experience using a novel formulation of 2-octyl cyanoacrylate for skin closure after surgical excision of cutaneous lesions. methods. we describe the results of 9 office-based dermatologic excisions in 8 patients utilizing a novel formulation of 2-octyl cyanoacrylate for skin closure. at two weeks of followup, all incisions were examined for cosmetic result and signs of infection as per the office’s standard of care. results. at follow-up, there were no signs of infection. one wound demonstrated mild tissue hypertrophy, while another showed very minimal skin separation (< 1mm) that did not require reintervention. no incidences of contact dermatitis, application discomfort, or burns were noted. patient satisfaction was high. conclusion. a novel formulation of 2-octyl cyanoacrylate topical adhesive demonstrates feasibility as a potential alternative to the use of sutures for skin closure following dermatologic excisions. larger studies are imperative to fully describe the outcomes associated with use of this new preparation. introduction skin january 2018 volume 2 issue 1 copyright 2018 the national society for cutaneous medicine 65 benefits in terms of ease of application,adverse reactions such as allergic contact dermatitis and exothermic burns have presented a barrier to use. 2 in this case series, we describe our experience using a novel formulation of 2-octyl cyanoacrylate (actabond-bergan medical products, inc., morris plains, nj) for skin closure following surgical excision of cutaneous lesions in a dermatologic office environment. the results of office-based cutaneous surgical excisions using a novel formulation of 2-octyl cyanoacrylate for wound closure following dermatologic excision procedures at a single practice in new york city were retrospectively examined. nine procedures (9 excisions in 8 patients) utilizing the adhesive were included. the decision to utilize the adhesive for closure (as opposed to sutures or staples) was made at the discretion of the surgeon. all wounds were closed in two layers: a single layer of interrupted 4-0 vicryl deep dermal sutures was used to approximate the subcutaneous tissues (as per standard practice in our office) and 2-octyl cyanoacrylate was applied for closure of the skin. patients were seen in follow-up two weeks following excision—in accordance with the standard post-surgical protocol of the office-based practice. at follow-up, all incisions were assessed for cosmetic result and signs of infection. the 9 lesions excised included 3 dysplastic nevi, 3 lipomas, 2 epidermoid cysts, and 1 squamous cell carcinoma (table 1). all lesions were located on the trunk or extremities. patients ranged from 27 to 68 years of age. table 1. clinical characteristics of included lesions lesion number age gender pathology location 1 41 male dysplastic nevus chest 2 32 male epidermoid cyst shoulder 3 53 female squamous cell carcinoma forearm 4 54 female epidermoid cyst shoulder 5 68 male lipoma forearm 6 25 male dysplastic nevus back 7 27 male dysplastic nevus back 8 68 male lipoma forearm 9 47 female lipoma thigh at two weeks, none of the incisions displayed erythema or signs of infection (figure 1). of the 8 lesions, 7 healed without any significant issues, although there was mild tissue hypertrophy along the closure case descriptions skin january 2018 volume 2 issue 1 copyright 2018 the national society for cutaneous medicine 66 line of one of the incisions. one closure exhibited very mild skin edge separation in the midpoint of the wound (< 1 mm), which was treated conservatively with observation and eventually healed. as skin-level sutures were not utilized, no suture tracts were visible along any of the lines of closure. none of the patients in this series experienced allergic contact dermatitis or discomfort/burning from exothermic reactions related to application of the adhesive. patient satisfaction with wound closure was, on average, 7.9 on a scale of 1-10. of the patients with a history of suture closure of a surgical wound, 88% preferred the adhesive to sutures. figure 1. representative photographs of surgical excision utilizing a novel formulation of 2-octyl cyanoacrylate for skin closure following excision of squamous cell carcinoma from the forearm. skin january 2018 volume 2 issue 1 copyright 2018 the national society for cutaneous medicine 67 the first use of a cyanoacrylate as a topical adhesive was described as early as the 1950s 3 . the concept of an alternative to suture closure of wounds remains attractive for multiple reasons, including decreased risk of occupational needle-stick injury, increased ease of application, and simplified wound care for patients without the need for suture removal. however, issues with dehiscence and local skin reactions have led to slow adoption by the surgical community, despite continuous efforts over time to improve adhesive formulation and limit these adverse events. 2,4 a recent randomized trial of 71 patients undergoing excision of cutaneous malignancies demonstrated that two such formulations (one of which was a cyanoacrylate) produced cosmetic outcomes on par with traditional suture closure, potentially opening the door for more widespread adoption by dermatologic surgeons. 5 our experience echoes the findings of this trial in terms of cosmetic result and patient satisfaction, but importantly, it introduces a newer formulation/delivery vehicle for 2-octyl cyanoacrylate that has not been extensively studied in a real-world setting. in addition to excellent results, we anecdotally noted improved ease of application in comparison to prior adhesive formulations. further, none of the patients undergoing wound closure with the adhesive experienced applicationrelated adverse events such as contact dermatitis or development of pain or burns resulting from exothermic reaction. these reactions have been a major deterrent to routine use of cyanoacrylates in the past; development of a formulation with a lower risk of these events has the potential to lead to increased adoption. 2 the present study carries several limitations. the case series nature of this work and the small number of included patients limit the conclusions which can be drawn. specifically, the lack of a comparison group makes attributing the good outcomes of this series definitively to the use of adhesive difficult, as other factors such as surgeon skill and patient characteristics could have played a role. a novel formulation of 2-octyl cyanoacrylate topical adhesive demonstrates feasibility as a potential alternative to the use of sutures for skin closure following dermatologic excision. in this small case series, the incidence of wound complications was low and patient satisfaction was high. further, there were no local complications of application. research studies need to be performed to further determine advantages that may exist using this closure method compared to standard techniques. conflict of interest disclosures: dr. svoboda served on an advisory board for jbt dermatology and received honorarium. dr. rigel serves as a consultant to bergan medical products, inc. funding: the adhesive used in the cases presented was provided to the authors by bergen medical products, inc. corresponding author: ryan m. svoboda, md, ms 35 e 35 th st., suite 208 new york, ny 10016 646-341-6468 (office) 212-689-5748 (fax) rmsvoboda@gmail.com discussion conclusion skin january 2018 volume 2 issue 1 copyright 2018 the national society for cutaneous medicine 68 references: 1. tajirian al, goldberg dj. a review of sutures and other skin closure materials. journal of cosmetic and laser therapy. 2010;12(6):296-302. 2. lefevre s, valois a, truchetet f. allergic contact dermatitis caused by dermabond((r)). contact dermatitis. 2016;75(4):240-241. 3. coover hn jf, sheere nh. chemistry and performance of cyanoacrylate adhesive. journal society of plastic surgery of england. 1959(1):5-6. 4. dumville jc, coulthard p, worthington hv, et al. tissue adhesives for closure of surgical incisions. the cochrane database of systematic reviews. 2014(11):cd004287. 5. bartenstein dw, cummins dl, rogers gs. a prospective, randomized, single-blind study comparing cyanoacrylate adhesives to sutures for wound closure in skin cancer patients. dermatologic surgery. 2017;43(11):1371-1378. powerpoint presentation presented at the fall clinical dermatology conference for pas & nps (fcpanp23), june 9–11, 2023, orlando, fl, usa figure 8. patient-reported work impact of sd n/a: not applicable; sd: seborrheic dermatitis. “the symptoms of my seborrheic dermatitis make me less likely to want to interact with people at work” “i feel i would be further along in my career if i didn't have seborrheic dermatitis” 58% agree “the symptoms of my seborrheic dermatitis have made me less confident at work” “the symptoms of my seborrheic dermatitis made me choose a different career path than i originally planned” 61% agree 59% agree 47% agree 50% yes no n/a ever missed work because of sd symptoms 47% yes 3% figure 5. patientand hcp-reported social life and personal relationships impact of sd hcp: healthcare provider; sd: seborrheic dermatitis. figure 2. hcp demographics hcp: n=601 included dermatologists and nps and pas specializing in dermatology. hcp: healthcare provider; np/pa: nurse practitioner/physician assistant; sd: seborrheic dermatitis. figure 1. patient demographics n=300. percentages may not add up to 100% due to rounding and acceptance of multiple responses. reference 1. dessinioti c, katsambas a. clin dermatol 2013;31:343–351. acknowledgements • this study was supported by arcutis biotherapeutics, inc. • thank you to the investigators and their staff for their participation in the trial • we are grateful to the study participants and their families for their time and commitment • writing support was provided by lauren ramsey, pharmd, alligent biopharm consulting llc, and funded by arcutis biotherapeutics, inc. disclosures rc, la, ch, ma, and mz are investigators and/or consultants for arcutis biotherapeutics, inc. and received grants/research funding and/or honoraria; dhc, dh, and ms are employees of arcutis biotherapeutics, inc. additional disclosures provided on request. raj chovatiya,1 lakshi aldredge,2 candrice heath,3 moises acevedo,4 david h. chu,5 diane hanna,5 melissa seal,5 matthew zirwas6 1northwestern university, chicago, il, usa; 2veterans administration portland health care system, portland, or, usa; 3temple university, philadelphia, pa, usa; 4park plaza dermatology, new york, ny, usa; 5arcutis biotherapeutics, westlake village, ca, usa; 6dermatologists of the central states, probity medical research, and ohio university, bexley, oh, usa patient and healthcare provider perspectives on the disease burden of seborrheic dermatitis in the united states: results from a national survey introduction • seborrheic dermatitis (sd) is a common chronic inflammatory skin disease with a worldwide prevalence of up to 5%1 • while sd is common, the physical and emotional burdens of sd have not been well characterized • the authors developed an online survey, conducted by the harris poll, to gain deeper insight into experiences and attitudes towards the disease among patients with sd and dermatology healthcare providers (hcps) • this poster reports patient and hcp perspectives on the physical and emotional burden of sd methods • the patient survey was conducted online from december 2021 through january 2022 among us adults diagnosed with sd by an hcp – results for age, gender, education, race/ethnicity, region, income, household size, and marital status were weighted, when necessary, to align the data with actual proportions in the population – a propensity score variable was also included to adjust for respondents’ propensity to be online • the hcp survey was conducted online from december 2021 through january 2022 among hcps specializing in dermatology (including dermatologists, nurse practitioners [nps], and physician assistants [pas]) who see ≥1 patient per week and ≥1 patient with sd per year – for dermatologists, results for years in practice, gender, and region were weighted, when necessary, to align the data with actual proportions in the population – for nps/pas, raw data were not weighted and are therefore only representative of the individuals who completed the survey results • the average age of patients in the survey was 40 years and 55% were male (figure 1) • 67% of the hcps were physicians, 24% were pas, and 10% were nps (figure 2) – the mean number of years in practice was 3.1 and the mean number of patients seen per week, for all skin conditions, was 158 • the majority of patients (71%) reported their symptoms as being moderate in severity – hcps may be underestimating the percentage of patients experiencing moderate symptoms • patients reported living with sd for an average of 3.6 years, with 20% waiting ≥6 years before seeking sd treatment (figure 3) • almost half of patients reported that sd negatively impacts their emotional (49%) and physical (42%) well-being “a lot/a great deal” – however, among the 85% of hcps who assessed quality of life (n=511), only 32% said living with sd has “a lot/a great deal” of negative impact on patients’ lives • patients with sd reported significant mental health impacts (figure 4) – 77% reported anxiety, 72% reported depression, and 69% reported anxiety about interacting with other people – hcps agreed that sd symptoms make patients feel anxiety (79%), depression (70%), and anxiety about interacting with other people (84%) • sd has a significant negative impact on patients’ social life/interactions (91%) and personal relationships (83%) (figure 5) – >70% of patients said sd can be isolating and other people around them did not understand the negative impact their sd symptoms have on their daily life – 86% of hcps agreed that others did not understand the negative impact of sd on patients’ lives • 82% of patients agreed that they feel embarrassed when people comment on their sd symptoms (figure 5) • 77% of patients agreed with the statement “my seborrheic dermatitis symptoms make people think that i have poor hygiene” (figure 5) – hcps agreed that patients feel embarrassed when someone comments on their sd symptoms (97%) and that patients’ sd symptoms make other people think they have poor hygiene (88%) • patients reported that sd has “a lot/a great deal” of negative impact on several aspects of their day-to-day life (figure 6) • almost all hcps agreed that sd has “a lot/a great deal” of negative impact on their patients’ day-to-day life (figure 7) conclusions • while most patients described their sd as moderate to severe and having a significant impact on their quality of life, hcps underestimated the patient-reported severity and level of impact on patients’ quality of life – patients’ social life and personal relationships suffer due to sd and most patients said others do not understand the negative impact of sd on their life • patients reported sd causes a considerable impact on their day-to-day life, including physical appearance, hygiene routine, clothing choices, and sleep • most patients said sd negatively impacts their self-esteem and multiple aspects of their mental health, causing anxiety and depression • the majority of patients reported sd impairs their ability to do their job, with almost half of patients having ever missed work due to sd symptoms • these insights highlight the immense patient burden associated with sd, impacting patients’ emotional, social, and work lives figure 3. patientand hcp-reported disease severity patients: n=300; hcps: n=601. hcp: healthcare provider. mean number of patients seen in a typical week mean number of patients with sd seen per year 323.7 patients 157.7 patients gender men: 41% women: 59% mean years of practice np/pa: 2.9 years dermatologist: 3.3 years patient-reported severity hcp-reported severity mild moderate severe 71% 16%13% 19% 40% 41% figure 4. patientand hcp-reported mental health impact of sd hcp: healthcare provider; sd: seborrheic dermatitis. figure 7. percent of hcps who reported “a lot/a great deal” of negative impact on their patients hcp: healthcare provider. figure 6. percent of patients who reported “a lot/a great deal” of negative impact 0 20 40 60 80 100 33% 41% 44% 46% 48% 48% 54% % patients ability to sleep social life personal relationships day-to-day life clothing choices daily hygiene routine physical appearance/ feeling attractive physical appearance /feeling attractive clothing choices daily hygiene routine 0 20 40 60 80 100 % h cp s 95%96% 91% 97% of hcps agree 88% of hcps agree “my seborrheic dermatitis symptoms make people think that i have poor hygiene” 19% 14% 31% 25% 28% 31% 13% 13% 91% 83% social life/ social interactions my personal relationships a little negative impact some negative impact a lot of negative impact a great deal of negative impact “i feel embarrassed when people comment on my seborrheic dermatitis symptoms” 77% of patients 82% of patients • 73% of patients stated living with sd negatively impacts their ability to do their job, specifically agreeing that (figure 8): – they would be further along in their career if they didn’t have sd (61%) – sd symptoms made them less confident at work (59%) – sd symptoms made them less likely to want to interact with people at work (58%) – sd made them choose a different career path than they originally planned (47%) • 47% of patients reported ever missing work due to sd symptoms mean age 40 years gender men: 55% women: 45% race/ethnicity black or white: 52% african american: 12% hispanic: 31% asian: 3% anxiety depression social anxiety “my seborrheic dermatitis symptoms cause me anxiety” “my seborrheic dermatitis symptoms make me feel depressed” “my seborrheic dermatitis symptoms make me anxious about interacting with other people” 90% of patients said living with sd negatively impacts their self-esteem, with 54% of them reporting it has “a lot/a great deal” of negative impact self-esteem 79% of hcps agree 77% of patients 70% of hcps agree 72% of patients 84% of hcps agree 69% of patients patient and healthcare provider perspectives on the disease burden of 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/untaggedrgbhandling /leaveuntagged /usedocumentbleed false >> << /allowimagebreaks true /allowtablebreaks true /expandpage false /honorbaseurl true /honorrollovereffect false /ignorehtmlpagebreaks false /includeheaderfooter false /marginoffset [ 0 0 0 0 ] /metadataauthor () /metadatakeywords () /metadatasubject () /metadatatitle () /metricpagesize [ 0 0 ] /metricunit /inch /mobilecompatible 0 /namespace [ (adobe) (golive) (8.0) ] /openzoomtohtmlfontsize false /pageorientation /portrait /removebackground false /shrinkcontent true /treatcolorsas /mainmonitorcolors /useembeddedprofiles false /usehtmltitleasmetadata true >> ] >> setdistillerparams << /hwresolution [2400 2400] /pagesize [612.000 792.000] >> setpagedevice no slide title this review highlights the evolution of oral formulations of tetracyclines most prescribed in dermatology. distinct differences, based on mor, have been noted in literature regarding reduction in some side effects and administration.4,5 tolerability and ease of use, as suggested by mor, have been correlated to improved compliance with treatment regimens.6,7 the data suggests that understanding the mor of tetracyclines may be an important consideration to guide individualized treatment and improve patient outcomes. the data reviewed demonstrates that these different mechanisms of release have unique side effect profiles and considerations for treatment which may impact tolerability, patient preference, and compliance with treatment regimens.8 dermatologists prescribe more oral antibiotics than any other specialty.1 from the mid-1950s to the early 1970s, the predominant oral antibiotic utilized to treat inflammatory skin disease was tetracycline.2 since then, there has been increased use of three newer generation tetracyclines. doxycycline was introduced in 1967, minocycline in 1971, and most recently sarecycline in 2018.2,11 these are available in various mechanisms of release (mor). the most common mors used in dermatology are immediate release (ir), delayed release (dr), and extended release (er). while clinicians prescribe all these mors, there is a lack of synthesized information regarding their impact on clinical considerations for use. the data presented here is intended to increase clinician understanding of mors, provide a quick reference source, and support individualized patient care. • to create a resource regarding the mor of oral tetracyclines used in dermatology.. • a systematic literature search of peer-reviewed publications was conducted over a 25-year period • the primary focus of the review was to summarize differences between ir, er, and dr and examine them pharmacologically and clinically • data was summarized into tabular format for ease of reference 1.barbieri js, bhate k, hartnett kp, fleming-dutra ke, margolis dj. trends in oral antibiotic prescription in dermatology, 2008 to 2016. jama dermatol. 2019;155(3):290–297. doi:10.1001/jamadermatol.2018.4944. 2. del rosso jq. oral doxycycline in the management of acne vulgaris: current perspectives on clinical use and recent findings with a new double-scored small tablet formulation. j clin aesthet dermatol. 2015;8(5):19-26. 3. neeraj, bhandari, et al. a review on immediate release drug delivery system. int. res j pharm. app sci., 2014; 4(1):78-87. 4. shargel, l., wu-pong, susanna, yu, a.b.c. (2012). applied biopharmaceutics & pharmacokinetics, 6e. mcgraw-hill education5. torok hm. extended-release formulation of minocycline in the treatment of moderate-to-severe acne vulgaris in patients over the age of 12 years. j clin aesthet dermatol. 2013;6(7):19-22. 6. moore a, ling m, bucko a, manna v, rueda mj. efficacy and safety of subantimicrobial dose, modified-release doxycycline 40 mg versus doxycycline 100 mg versus placebo for the treatment of inflammatory lesions in moderate and severe acne: a 7. randomized, double-blinded, controlled study. j drugs dermatol. 2015;14(6):581-586. 8. kircik, l., bikowski, j. oral formulations optimizing outcomes and enhancing adherence through formulation advancements. supplement to practical dermatology, december 2010. 9. targadox® (doxycycline hyclate usp) (2020, july). prescribing information. scottsdale, az, usa: journey medical corporation. 10. acticlate® (doxycycline hyclate) (2017, oct). prescribing information. winchester, ky, usa: catalent pharma solutions. 11. seysara® (sarecycline) (2020, jun). prescribing information. exton, pa, usa: almirall llc. 12. doryx® (doxycycline hyclate) (2015, aug). prescribing information. greenville, nc, usa: mayne pharma, inc. 13. doryx® mpc (doxycycline hyclate delayed-release tablets) (2020, jun). prescribing information. greenville, nc, usa: mayne pharma, inc. 14. solodyn® (minocycline hcl) (2017, july). prescribing information. bridgewater, nj, usa: valeant pharmaceuticals north america llc. 15. minolira™ (minocycline hydrochloride) extended release) ( 2018, june). prescribing information. charleston, sc, usa: epi health, llc. 16. ximino™ (minocycline hydrochloride) extended-release capsules. (2017, april). prescribing information. cranbury, nj, usa: sun pharmaceutical industries, inc. 17. minocin® (minocycline hydrochloride) pellet-filled capsules., (2010, aug). prescribing information. cranford, nj. usa: triax pharmaceuticals, llc. a. dr. kwong is in pediatric dermatology private practice, jacksonville, fl. b. dr. baldwin is medical director, acne treatment and research center, brooklyn, ny and clinical associate professor of dermatology, rutgers robert wood johnson medical center, new brunswick, nj c. ms. glaab and ms. schreiber are employed at mayne pharma d. ms. hignett attends ucf college of medicine, orlando, fl. this poster was sponsored by mayne pharma. introduction review of mechanisms of release of commonly prescribed tetracyclines pearl kwong md, phd, faad a, hilary baldwin md, faad b, debbie glaab msn, cpnp-ac c, rhonda schreiber ms, rn c, emma hignett bs d table 1: mor quick reference sixteen publications related to mor were identified from this review. consistently, the tetracycline derivatives doxycycline and minocycline were the most frequently used to treat inflammatory skin disease with a long and favorable track record of effectiveness and safety.2 although newer and with fewer publications, sarecycline was shown to be both efficacious and safe in treating acne vulgaris.11 currently doxycycline is available in both immediate and delayed-release formulations, minocycline in immediate and extended release, and sarecycline in immediate release. delayed and extended release formulations were developed to address tolerance issues, achieve desired therapeutic objectives, and improve patient compliance concerns identified with the original immediate release formulations.4 all 3 mors have value in treatment regimens and may improve patient outcomes when fully understood and utilized in a manner that maximizes their formulation benefits to meet individual needs. table 1 below provides a quick reference regarding mor for the currently available branded tetracycline products. *all trademarks and registered trademarks are the property of their respective owners conclusions ir formulations release most of the active drug very quickly after oral administration.3 dr formulations are enteric coated, allowing most of the active drug to bypass the upper gi tract.2 er formulations release active drug over a longer period of time to provide stabilized pharmacodynamic effect.5 results objective methods figure 1: mechanisms of release affiliations immediate release delayed release extended release considerations for treatment • active drug released in stomach absorbed in small intestine3,4 • intended to achieve rapid onset of pharmacodynamic effect4 • can also induce or exacerbate gi side effects8 and vestibular side effects (minocycline only)4,5,17 • impact of food and dairy varies among ir products and prescribing information should be checked prior to dosing9,10,11,15,16,17 • active drug released and absorbed in the small intestine2,4 • intended to reduce side effects related to upper gi tract exposure4 • can take with or without food12,13 • can take with dairy12,13 • active drug released in the stomach and absorbed in small intestine4,5 • intended to reduce systemic side effects and allow for less frequent dosing 4, 5 • longer half-life with more consistent systemic exposure5 • can take with or without food14,15,16 • impact of dairy varies among er products and prescribing information should be checked prior to dosing14,15,16 examples • doxycycline hyclate (targadox®, acticlate®)9,10 • sarecycline (seysara®)11 • minocin® (minocycline hydrochloride)17 • doxycycline hyclate (doryx®)12 • doxycycline hyclate modified polymer coating (doryx® mpc)13 • minocycline hcl (solodyn®)14 • minocycline hydrochloride (minolira™)15 • minocycline hydrochloride (ximino™)16 references skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 82 research letter sun protection policies in juvenile detention centers in pennsylvania christen samaan, bs1, monica valentin, md2, richard schreiber, md3, joslyn kirby md, ms, m.ed4 1geisinger commonwealth school of medicine, scranton, pa 2medstar washington hospital center, washington, dc 3geisinger holy spirit, camp hill, pa 4penn state milton s. hershey medical center, hershey, pa the incidence rate of skin cancer is increasing in the united states and deaths from melanoma have been increasing dramatically. childhood sunburns is an important risk factor for melanoma, and may increase risk by nearly 2-fold.1 more than half of a person’s lifetime uv exposure typically occurs during childhood and adolescence.2 effective sun protection is practiced by less than one-third of u.s. youth. 2 therefore, primary prevention and early detection of skin cancer in childhood is important to reduce the risk of developing skin cancer.3 the centers for disease control and prevention (cdc) developed a set of guidelines to provide schools with a comprehensive approach to preventing skin cancer among adolescents and young people.4 however, these guidelines are not specifically aimed at similar school-aged children who are in different environments but also have similar sun exposure. the objective of this study was to determine the prevalence of sun protection policies, environmental features, and attitudes in institutions responsible for school-aged populations in juvenile detention centers. the survey was designed to measure all seven components of the cdc guidelines: policy; environmental change; education; family involvement; professional development; health services; and evaluation. juvenile detention centers were included if they are classified as secure detention centers, secure confinement centers, or non-secure residential programs. a 26-item survey queried current sun protection policies, amount of time residents spent outside during peak sun hours, the use of sunscreen and sun-protective clothing by residents and staff, and attitudes about the importance of sun protection. the survey was piloted through the county commissioners to determine readability and face validity of the instrument and sent via e-mail to all juvenile detention centers in pennsylvania (n=19). data was collected between 05/18/2018 and 06/08/2018 and centers were sent 2 reminders by e-mail. data analysis was conducted using spss 22 and data were analyzed primarily by calculating percentages. for questions using a 5-point likert scale, respondents who endorsed an item with a 4 or 5 were coded as agreeing with the statement. skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 83 overall, 63.2% (n=12) of the juvenile detention centers in pennsylvania responded to the survey. 41.7% (n=5) of the centers were secure detention centers, 25% (n=3) secure confinement centers, and 33.3% (n=4) non-secure residential programs. two facilities (16.7%) reported having written policy that governs resident uv protection. all of the facilities (100%) responded with sometimes or always scheduling activities during peak sun hours. facilities were asked about shade producing structures and permission to wear hats, sunglasses, and sunscreen without a provider’s note as options to govern resident uv protection. all the facilities (100%) reported shade-producing structures, but 83.3% (n=10) cover less than 25% of the outdoor activity areas. of the 12 centers, 50% (n=6) allow residents to wear hats, 25% (n=3) allow residents to wear sunglasses, 66.7% (n=8) allow residents to wear sunscreen without a pcp note, and 25% (n=3) provide sun protection education (figure 1). only 1 facility utilized none of the 4 options (shade producing structures, hats, sunglasses, and sunscreen). 6 facilities (50%) utilized 1 of the options, 1 facility (8.3%) utilized 2 of the options, 3 facilities (25%) utilized 3 of the options, and 1 facility (8.3%) utilized all 4 of the options. (shade producing structures was counted as yes if it figure 1: percent of facilities that allow residents to use different sun protection options. covered more than 25% of the outdoor activity areas). allowing residents to wear sunscreen without a provider’s note was the method most often utilized. five facilities (41.7%) reported having staff trained or knowledgeable about sun protection behaviors. facilities with trained staff reported higher rates of instructing residents about practicing sun protection behaviors. the facilities that did not have staff trained or knowledgeable about sun protection behaviors reported never or less often instructing residents about sun protection. most (66.7%, n=8) of the centers agreed that excessive sun exposure during childhood is an important health concern, but only 25% (n=3) agree that their facility has adequate measures to protect their residents from the sun (figure 2). only 08.3% (n=1) of respondents have seen the cdc school guidelines. the cdc’s guidelines include recommendations for schools to encourage skin cancer prevention on school property and elsewhere. however, these guidelines are not equally implemented across all the institutions responsible for school-aged populations, such as children in juvenile detention centers. thus, we may be missing figure 2: facility attitudes towards sun exposure. skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 84 an important educational opportunity in an already vulnerable community. in the school setting, a study by correnti et al showed inadequate youth sun-protective behavior (eg, sunscreen use) despite rising skin cancer rates in children.6 pollitt et al further explored sun-protective behavior specifically in low socioeconomic (ses) status population. the study focused on the association of low socioeconomic status with more advanced melanoma at diagnosis and decreased survival.7 the authors identified that the association is due to decreased knowledge about the risk of melanoma and associated risk factors among low-ses individuals. they suggest the need to increase education about skin cancer among lower-ses patients and increase awareness of socioeconomic disparities in clinical communication and care.7 limitations of our study include the small number of centers in pa that qualified for participation in the survey. next steps include expanding the survey to more states and comparing sun protection practices of centers in different uv intensity regions. among public juvenile detention centers in pa, we found an absence of policies to reduce sun exposure and a lack of knowledge about the cdc guidelines to prevent skin cancer. despite these results, administrators are largely in favor of stronger policies and believe sun exposure is an important health issue. conflict of interest disclosures: none. funding: none. corresponding author: christen b. samaan bs geisinger commonwealth school of medicine scranton, pa christensamaan1@gmail.com references: 1. american cancer society. cancer facts & figures 2018. atlanta: american cancer society; 2018. 2. dennis lk, vanbeek mj, beane freeman le, smith bj, dawson dv, coughlin ja. sunburns and risk of cutaneous melanoma, does age matter: a comprehensive meta-analysis. ann of epidemiol. 2008;18(8):614-627. 3. dono j, ettridge ka, sharplin gr, wilson cj. the relationship between sun protection policies and practices in schools with primary-age students: the role of school demographics, policy comprehensiveness and sunsmart membership. health edu res. 2014;29(1):1-12. 4. guidelines for school programs to prevent skin cancer. centers for disease control and prevention. https://www.cdc.gov/mmwr/preview/ mmwrhtml/rr5104a1.htm. 5. nahar vk. skin cancer prevention among school children: a brief review. cent eur j public health. 2013;21(4):227-32. 6. correnti cm, klein dj, elliott mn, veledar e, saraiya m, chien at, schwebel dc, mrug s, tortolero sr, cuccaro pm, schuster ma, chen sc. racial disparities in fifth-grade sun protection: evidence from the healthy passages study. pediatr dermatol. 2018. 7. pollitt ra, swetter sm, johnson tm, patil p, geller ac. examining the pathways linking lower socioeconomic status and advanced melanoma. cancer. 2012;118:4004-4013. mailto:christensamaan1@gmail.com presented at the 13th winter clinical dermatology conference, january 12 –17, 2018, maui, hi, usa clinical efficacy of tildrakizumab in patients with chronic plaque psoriasis over 2 years of treatment: results from long-term extensions to 2 phase 3 clinical studies kim papp,1 kristian reich,2 andrew blauvelt,3 diamant thaçi,4 rodney sinclair,5 stephen k tyring,6 nicole cichanowitz,7 stuart green,7 qing li,7 carmen la rosa7 1probity medical research, waterloo, on, canada; 2sciderm research institute and dermatologikum hamburg, hamburg, germany; 3oregon medical research center, portland, or, usa; 4comprehensive center for inflammation medicine, university medical school schleswig-holstein, university of lübeck, lübeck, germany; 5university of melbourne, melbourne, vic, australia; 6department of dermatology, university of texas, houston, tx, usa; 7merck & co., inc., kenilworth, nj, usa background • tildrakizumab is a high-affinity, humanized, anti–il-23p19 monoclonal antibody that has demonstrated efficacy in the treatment of chronic plaque psoriasis in 2 phase 3 studies: resurface 1 (nct01722331) and resurface 2 (nct01729754)1 • both of these studies have an optional long-term extension, each with an additional treatment period of up to 192 weeks objective • preliminary evaluation of maintenance of response data in patients who were responders to tildrakizumab upon entering the extension periods and who maintained response a year into the extensions (a total of at least 2 years of treatment including base and extension periods) methods base studies • the resurface base studies are 3-part, double-blinded, randomized, placebo-controlled studies in patients with moderate to severe chronic plaque psoriasis • inclusion criteria included age ≥18 years, body surface area involvement ≥10%, physician’s global assessment (pga) score ≥3, and psoriasis area and severity index (pasi) ≥12 • in the base studies, tildrakizumab 200 and 100 mg were evaluated for 64 weeks (resurface 1) and 52 weeks (resurface 2) – in part 1 of the studies (weeks 1–12), patients were randomized to subcutaneous tildrakizumab 200 mg, tildrakizumab 100 mg, or placebo, and treatment was administered at weeks 0 and 4. in resurface 2, there was an additional treatment arm of etanercept 50 mg administered twice weekly – in part 2 (weeks 12–28), patients previously receiving placebo were rerandomized to tildrakizumab 200 mg or 100 mg and received treatment at weeks 12, 16, and 28. in resurface 2, the dose in the etanercept arm was 50 mg once weekly extension studies • eligibility criteria for the extension included: – patients completed the base studies and chose to continue the optional long-term extensions – patients achieved ≥50% improvement in pasi (pasi 50) at the end of the base studies – in resurface 1 only, patients had to have received an active dose of tildrakizumab within 12 weeks of the end of the base study • patients received the same dose of tildrakizumab (200 or 100 mg every 12 weeks) as was received at the completion of the base studies; administration was open label after database lock for the base studies • efficacy objective for the extension period: – evaluation of the maintenance of efficacy endpoints (ie, proportion of pasi 50, 75, 90, and 100 responders 1 year into the extension among pasi 50, 75, 90, and 100 responders at the start of the extension) – prespecified to be based on observed data, with no statistical analyses planned for comparison between doses – the primary efficacy population was the full analysis set, defined as patients with at least 1 dose of extension treatment based on assigned treatment • safety objective for the extension period: – evaluation of adverse events (aes) for up to 5 years; prespecified aes of interest were summarized by treatment over time – yearly and cumulative (base and extension combined) incidence rates were calculated results • in resurface 1, 772 patients entered the study, 638 patients completed the base period, and 506 patients entered the extension; in resurface 2, 1090 patients entered the study, 756 patients completed the base period, and 731 patients entered the extension (figure 1) table 1. baseline characteristics for patients entering extension period resurface 1 resurface 2 til 100 mg til 200 mg total til 100 mg til 200 mg total subjects in population, n 239 267 506 382 349 731 male 159 (66.5) 183 (68.5) 342 (67.6) 291 (76.2) 242 (69.3) 533 (72.9) age, mean (sd), y 46.9 (13.0) 47.1 (13.0) 47.0 (13.0) 44.2 (13.2) 45.6 (12.8) 44.9 (13.0) race, white 163 (68.2) 173 (64.8) 336 (66.4) 352 (92.1) 329 (94.3) 681 (93.2) baseline pasi score, mean (sd) 20 (7.6) 21.3 (9.6) 20.7 (8.7) 19.8 (7.6) 19.3 (6.9) 19.6 (7.3) weight, mean (sd), kg 87.1 (24.4) 87.8 (24.2) 87.5 (24.3) 88.4 (21.4) 89.0 (21.5) 88.7 (21.4) body surface area, mean (sd), % 30.2 (17.5) 31.7 (19.6) 31.0 (18.6) 32.6 (18.0) 30.1 (15.8) 31.4 (17.0) data in table are n (%) unless otherwise specified. pasi, psoriasis area and severity index; til, tildrakizumab. table 2. two-year cumulative number (rate) of patients with aes of interest resurface 1 resurface 2 til 100 mg n (exposure adjusted rate per 100 py) til 200 mg n (exposure adjusted rate per 100 py) til 100 mg n (exposure adjusted rate per 100 py) til 200 mg n (exposure adjusted rate per 100 py) severe infections 5 (0.8) 6 (0.8) 7 (0.8) 9 (1.1) malignancies 6 (0.9) 2 (0.3) 4 (0.5) 7 (0.9) nonmelanoma skin cancer 2 (0.3) 2 (0.3) 3 (0.4) 4 (0.5) melanoma skin cancer 0 0 1 (0.1) a 0 confirmed mace 3 (0.5) 2 (0.3) 0 1 (0.1) deathsb 0 0 2 (0.2) 1 (0.1) drug-related hypersensitivity aes 2 (0.3) 1 (0.1) 2 (0.2) 2 (0.2) athe reported case of melanoma was melanoma in situ; bnot related to study medication. asat population. ae, adverse event; asat, all subjects as treated; mace, major adverse cardiac event; py, patient-years; til, tildrakizumab. references 1. reich et al. lancet. 2017;390(10091):276–288. acknowledgments we thank the patients for their participation. these studies were funded by merck & co., inc., kenilworth, nj, usa. editorial assistance and layout were provided by fishawack communications and funded by sun pharmaceutical industries, inc. disclosures kp has served as an advisor, paid speaker and/or clinical study investigator for abbvie, akros, allergan, amgen, anacor, astellas, astrazeneca, baxalta, baxter, boehringer ingelheim, bristol myers squib, canfite, celgene, coherus, dermira, dow pharma, eli lilly, forward pharma, galderma, genentech, glaxosmithkline, janssen, kyowa hakko kirin, leo, medimmune, meiji seika pharma, merck sharp & dohme, merck serono, mitsubishi pharma, novartis, pfizer, regeneron, roche, sanofi-aventis/genzyme, takeda, ucb, valeant. kr has served as an advisor, paid speaker and/or clinical study investigator for abbvie, affibody, amgen, biogen, boehringer ingelheim pharma, celgene, centocor, covagen, forward pharma, glaxosmithkline, janssen-cilag, leo, lilly, medac, merck sharp & dohme corp., novartis, ocean pharma, pfizer, regeneron, sanofi, takeda, ucb pharma, xenoport. ab has served as a scientific adviser and/or clinical study investigator for abbvie, aclaris, allergan, almirall, amgen, boehringer ingelheim, celgene, dermavant, dermira, inc., eli lilly and company, genentech/roche, glaxosmithkline, janssen, leo, merck sharp & dohme, novartis, pfizer, purdue pharma, regeneron, sandoz, sanofi genzyme, sienna pharmaceuticals, sun pharma, ucb pharma, valeant, and vidac, and as a paid speaker for eli lilly and company, janssen, regeneron, and sanofi genzyme. dt has served as an advisor, paid speaker and/or clinical study investigator for abbvie, almirall, amgen, astellas, biogen-idec, boehringer-ingelheim, celgene, dermira, dignity, eli lilly, forward-pharma, galapagos, glaxosmithkline, leo, janssen-cilag, maruho, msd, mitsubishi pharma, mundipharma, novartis, pfizer, roche, roche-posay, sandoz, xenoport. rs has served as an advisor, paid speaker and/or clinical study investigator for amgen, bayer, boehringer ingelheim, celgene, coherus biosciences, cutanea, eli lilly, glaxosmithkline, janssen, leo pharma, medimmune, merck & co., msd, novartis, oncobiologics, pfizer, regeneron, roche and samson clinical. skt is a clinical study investigator for merck & co. nc, sg, ql, and clr are employees of merck & co, inc. these data were previously presented at the 26th european academy of dermatology and venereology congress, september 13–17, 2017, geneva, switzerland. figure 1. patient flow completed week 64 til 100 mg n=297randomized n=772 completed week 64 til 200 mg n=341 entered extension til 100 mg n=239 entered extension til 200 mg n=267 extension 1 year til 100 mg n=219 extension 1 year til 200 mg n=255 base study resurface 1 extension study completed week 52 til 100 mg n=394randomized n=1090 completed week 52 til 200 mg n=362 entered extension til 100 mg n=382 entered extension til 200 mg n=349 extension 1 year til 100 mg n=355 extension 1 year til 200 mg n=333 base study resurface 2 extension study at week 28 of each study, as specified in the trial designs, tildrakizumab nonresponders were discontinued and etanercept responders (resurface 2) were discontinued; upon completion of base periods, subjects with at least pasi 50 were provided the option to enter the extensions. til, tildrakizumab. figure 2. maintenance of pasi 75 response from end of base period through extension periods (a) resurface 1 and (b) resurface 2 100 80 60 40 20 0 r es po nd er s m ai nt ai ni ng w ee k 64 r es po ns e, % 209 218 til 100: n= til 200: n= 203 212 202 215 202 214 197 203 195 208 base period extension period a 64week: 0 12 24 36 48 100 80 60 40 20 0 r es po nd er s m ai nt ai ni ng w ee k 52 r es po ns e, % 347 305 til 100: n= til 200: n= 326 293 340 301 341 298 334 296 327 293 base period extension period b 52week: 8 12 24 36 48 til 100 mg til 200 mg til 100 mg til 200 mg fas population; observed data. patients entering the extension after 64 weeks (resurface 1) or 52 weeks (resurface 2) were at least partial responders (ie, pasi ≥50). n=number of subjects with data. fas, full analysis set; pasi, psoriasis area and severity index; til, tildrakizumab. figure 4. overall efficacy from end of base period through extension periods (a) resurface 1 and (b) resurface 2 100 80 60 40 20 0 r es po nd er s, % 209 218 til 100: n= til 200: n= 199 208 198 209 188 211 189 189 184 206 base period extension period 100 80 60 40 20 0 r es po nd er s, % 52 8 12 24 36 48 347 305 til 100: n= til 200: n= 325 290 334 295 341 289 321 285 314 279 base period extension period pasi 75a b 100 80 60 40 20 0 r es po nd er s, % 128 140 til 100: n= til 200: n= 133 137 125 142 123 146 120 132 113 137 base period extension period pasi 90 100 80 60 40 20 0 r es po nd er s, % 64week: 0 12 24 36 48 73 72 til 100: n= til 200: n= 61 69 63 75 62 78 59 63 49 59 64week: 0 12 24 36 4864week: 0 12 24 36 48 base period extension period 100 80 60 40 20 0 r es po nd er s, % 52 8 12 24 36 48 263 195 til 100: n= til 200: n= 246 194 261 205 261 212 240 206 228 202 52 8 12 24 36 48 base period extension period 100 80 60 40 20 0 r es po nd er s, % week: 131 99 til 100: n= til 200: n= 132 94 139 98 128 100 125 105 111 104 base period extension period pasi 100 til 100 mg til 200 mg til 100 mg til 200 mg til 100 mg til 200 mg til 100 mg til 200 mg til 100 mg til 200 mg til 100 mg til 200 mg fas population; observed data. n=number of responders. fas, full analysis set; pasi, psoriasis area and severity index; til, tildrakizumab. figure 3. overall efficacy after 2 years of treatment with tildrakizumab 100 90 80 70 60 50 40 30 20 10 0 pasi 75 pasi 90 pasi 100 pga (0,1) p at ie nt s, % 84 52 22 81 54 23 88 66 34 84 61 33 58 55 66 67 til 100 n=219 resurface 1 til 200 n=255 til 100 n=355 til 200 n=333 resurface 2 fas population; observed data. patients entering the extension after 64 weeks (resurface 1) or 52 weeks (resurface 2) were at least partial responders (ie, pasi ≥50). fas, full analysis set; pasi, psoriasis area and severity index; pga, physicians’ global assessment; til, tildrakizumab. conclusions • tildrakizumab 100 mg or 200 mg demonstrated maintenance of efficacy in the treatment of moderate to severe chronic plaque psoriasis for at least 2 years of treatment • over a cumulative 2-year treatment period in patients enrolled in resurface 1 and resurface 2, tildrakizumab 200 and 100 mg were well-tolerated with a low rate of aes of interest• at the base study baseline, disease characteristics of patients who went on to enter the extension were similar between the 2 studies, and between the tildrakizumab 100-mg and 200-mg groups (table 1) – the percentage of white patients was lower in resurface 1 than 2 because resurface 1 included sites in japan, whereas resurface 2 did not efficacy • pasi responses were maintained in most patients from the end of the base period through the extension period: – in resurface 1, in patients entering the extension on tildrakizumab 200 mg, pasi 50/75/90/100 was maintained by 97%/91%/82%/63% (out of 255/208/135/70 patients with data at 1 year); in patients on tildrakizumab 100 mg, pasi 50/75/90/100 was maintained by 98%/90%/74%/53% (out of 219/195/121/70 patients with data at 1 year) (figure 2a) – in resurface 2, in patients entering the extension on tildrakizumab 200 mg, pasi 50/75/90/100 was maintained by 97%/88%/84%/70% (out of 330/293/191/97 patients with data at 1 year); for those on tildrakizumab 100 mg, pasi 50/75/90/100 was maintained by 99%/92%/84%/66% (out of 352/327/249/125 patients with data at 1 year) (figure 2b) • after 2 years of treatment with tildrakizumab, including the base and extension periods, 84% and 88% of patients who received tildrakizumab 100 mg achieved pasi 75 in resurface 1 and resurface 2, respectively. similarly, in the tildrakizumab 200-mg groups, 81% and 84% of patients achieved pasi 75 in resurface 1 and resurface 2, respectively (figure 3) safety • after 2 years of treatment with tildrakizumab, the cumulative number of patients with prespecified aes was low in both the 200-mg and 100-mg groups in both studies (table 2) • overall, the proportions of patients achieving pasi 75/90/100 responses were stable during the extension period (figure 4) skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 960 compelling comments history in the making: the transformative impact of tiktoktm on dermatology kennedy sparling, bs1 1 university of arizona, college of medicine pheonix, phoenix, az have you heard the terms ‘jello skin’, ‘retinol sandwiching’, or ‘skin cycling’? if not, you probably haven’t ventured much into the skincare side of the popular social media platform, tiktoktm. tiktoktm, launched in 2016, has transformed the way in which people consume and share information1. through its short-form videos, tiktoktm goes beyond entertainment and has served as a hub for sharing information, including in the field of education and healthcare. this platform has provided dermatology professionals with a unique space to share their expertise to the public. dermatologists, such as dr. muneeb shah (@dermdoctor) and dr. zion ko lamm (@dr.zionko), have taken this opportunity to share their expert opinions, debunk myths, and address common skincare concerns. in fact, in an analysis of dermatology on tiktoktm completed in 2021, 39% of the 544 videos analyzed were created by healthcare providers2. as technology continues to serve as a source for patients to obtain information, it is crucial for healthcare professionals to embrace this platform and be aware of the trends so they can actively participate in shaping the future of dermatology. it’s important to note that with the vast amount of information and videos on tiktoktm, there exists a potential for misinformation. for example, a trend termed ‘reverse skincare’ emerged in 2022 and was made popular by influencer, ava lee (@glowwithava). this trend advocated for the reversal in order of skin care product application, starting with occlusives3. since its emergence, many dermatologists have debunked this trend as ineffective and potentially harmful depending on the individual3. by learning from the past, healthcare professionals have the opportunity to use tiktoktm to correct misinformation and promote evidence-based practices to the public. in addition to providing a space for dermatologists, tiktoktm has played an important role in increasing public awareness of dermatologic conditions. in the same study mentioned prior, videos with the hashtag of the top five dermatologic diagnoses gained a total of 2.5 billion views2. with patients generating 45% of the study’s videos, it’s clear that these firsthand accounts are also very prevalent on the platform2. many users have openly discussed their experiences and often arduous journeys with various skin introduction discussion skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 961 conditions. these individuals not only have served to raise awareness of their condition, but some, such as alex griswold (@alexgriswold), have also been alerted of possible life-threatening skin conditions, encouraging them to seek professional advice. through fostering a sense of community, this social media platform has offered solace to those facing dermatologic conditions, reminding them they are not alone and to seek professional help when they need it. while a short-lived history thus far, tiktoktm has already transformed the healthcare industry, especially in the field of dermatology. it’s essential for healthcare providers to remain attuned to this emerging platform so they can learn from the past and further enhance their patient care going forward. conflict of interest disclosures: none funding: none corresponding author: kennedy sparling, bs university of arizona, college of medicine phoenix 475 n 5th st, phoenix, az 85004 phone: 702-860-9684 email: ksparling@arizona.edu references: 1. tidy, j. & smith galer, s. (2020, august 5). tiktok: the story of a social media giant. bbc news. https://www.bbc.com/news/technology53640724 2: nguyen, m., youssef, r., kwon, a., chen, r., & park, j. h. (2021). dermatology on tiktok: analysis of content and creators. international journal of women's dermatology, 7(4), 488–489. https://doi.org/10.1016/j.ijwd.2021.04.006 3: sobotka, m. (2023, april 18). the risks of tiktok’s reverse skin care trend. skin inc. https://www.skininc.com/business/trends/new s/22605108/dr-dennis-gross-skincare-therisks-of-tiktoks-reverse-skin-care-trend conclusion skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 137 research letter increase in google trends regarding telogen effluvium due to covid-19 jasmine garg, ba1, abigail cline, md, phd2, frederick pereira, md2 1new york medical college, valhalla, new york 2department of dermatology, new york medical college, valhalla, new york a long-term sequela of covid-19 that has garnered attention in both the medical literature and the lay press is telogen effluvium (te). the incidence of te in patients recovering from covid-19 is approximately 27%, and it is more common in women than men.1 te has been cited as an adverse effect from both viral infection and stressful conditions, such as job loss from the pandemic. however, it has been difficult to confirm if te is due to covid infection itself since not everyone was tested properly. because many dermatology offices have closed during the pandemic, patients concerned about their hair loss are turning to online resources to learn more about their condition.2 to determine if there is an increased public interest in te, we investigated the number of people conducting online searches for te secondary to covid-19. google trends reflects search interest in various topics.3 using google trends, we analyzed the patterns of google search queries with the search terms “covid hair loss”, “telogen effluvium” and “hair loss”. the search timeline was set from 5/1/20 to 8/16/20. a google trends score ranges from zero to one hundred. a score of one hundred is considered the date when the search term was used at peak frequency. we also used google trends to ascertain where in the united states these search terms were most used abstract objective: the purpose of this study was to assess the public interest in the united states of telogen effluvium before and after the covid-19 pandemic in order to investigate the best therapeutic interventions for dermatologists in the future. methods: we performed google trendstm search for “covid hair loss”, “telogen effluvium” and “hair loss” between 5/1/20 and 8/16/20. conclusion: all three terms have increased in popularity for search terms since mid-march and were the most prevalent in the states that experienced the earliest increase in number of coronavirus cases. introduction methods skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 138 figure 1: the change in popularity of “covid hair loss”, “telogen effluvium” and “hair loss” in google trendstm before and after covid-19 pandemic in the usa from 5/1/19-8/10/20. in the united states there has been an increase in all three search terms since midmarch (figure 1), and all three search terms are continuing to rise. comparing the number of searches made at the same time period one year prior (5/1/19 to 8/16/19), use of the search term “hair loss” increased by 11% and use of the term “telogen effluvium” increased 14%. this provides indirect evidence that the incidence of te is rising. the largest number of searches for the terms “covid hair loss”, “hair loss” and “telogen effluvium” corresponded to those states that were the earliest to experience sudden increases in the number of covid table 1. google trends score and average covid19-positive rate per 100,000 state google trends score* average covid-19 rate per 100,000* new york 100 1576.7 district of columbia 86 1385.1 nevada 81 747.8 new jersey 79 1878.6 maine 79 216.9 * date range 5/1/2020 to 8/16/2020 19 cases within their borders.4 new york and new jersey topped the list both in terms of google trend searches and in covid-19 infection rates per 100,000 (table 1).5 te secondary to covid-19 may be on the rise. in our own new york safety-net hospital, there was a 400% increase in te cases compared to the year prior.6 this report highlights that many patients are seeking answers and reassurance as seen in our 0 20 40 60 80 100 120 5/5/2019 7/5/2019 9/5/2019 11/5/2019 1/5/2020 3/5/2020 5/5/2020 7/5/2020 covid hair loss telogen effluvium hair loss results discussion skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 139 own dermatology clinic. as clinics and offices reopen, dermatologists should expect increased numbers of te cases, and they should prepare themselves to educate and treat these patients. conflict of interest disclosures: none funding: none corresponding author: jasmine garg, ba new york medical college 1410 old farm road valhalla, new york 10595 phone: 503-550-6426 email: jgarg@student.touro.edu references: 1. turkmen, d, altunisik, n, sener, s, et al. evaluation of the effects of covid‐19 pandemic on hair diseases through a web‐based questionnaire. dermatol ther. 2020 june 28;el3923 https://doi.org/10.1111/dth.13923 2. rivetti, n. and barruscotti, s. management of telogen effluvium during the covid‐19 emergency: psychological implications. dermatol ther. 2020 may 22;e13923. doi:10.1111/dth.13648 3. effenberger, m., kronbichler, a., shin, j. et al. association of the covid-19 pandemic with internet search volumes: a google trendstm analysis. int j infect dis. 2020 apr 17; 202095, 192–197. https://doi.org/10.1016/j.ijid.2020.04.033 4. oster, alexandra m, et al. “trends in number and distribution of covid-19 hotspot counties united states, march 8–july 15, 2020.” centers for disease control and prevention, centers for disease control and prevention, 20 aug. 2020, www.cdc.gov/mmwr/volumes/69/wr/mm6933e2.h tm. 5. cdc covid data tracker. (n.d.). retrieved january 12, 2021, from https://covid.cdc.gov/covid-datatracker/#trends_dailytrendscases 6. cline, a, kazemi, a, moy, j, et al. surge in the incidence of telogen effluvium in minority predominant communities heavily impacted by covid-19. j am acad dermatol. 2020 oct 5. https://doi.org/10.1111/dth.13923 https://doi.org/10.1016/j.ijid.2020.04.033 http://www.cdc.gov/mmwr/volumes/69/wr/mm6933e2.htm http://www.cdc.gov/mmwr/volumes/69/wr/mm6933e2.htm skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 439 compelling comments vitiligo and beauty ashley e. brown, bs1, caroline t. starling, bs1 1the university of texas health science center at houston, mcgovern medical school, houston, tx vitiligo is an autoimmune condition targeting select melanocytes in the epidermis producing segmental areas of depigmentation. there is a predilection for involvement on the face and hands, which can have devastating psychological results including lowered self-esteem, anxiety, and depression. individuals with extensive vitiligo, dark skin, or onset at an earlier age are especially affected.1 winnie harlow, born chantelle brownyoung, has defied the norms of beauty by entering the modeling industry despite suffering from vitiligo (figure 1). during her childhood she became self-conscious after being bullied, by being called “cow” and “moo.” harlow later said, “i don't actually think i'm ugly i think i'm beautiful. so where did i get this idea i wasn't? from someone else.” 2 she has become a well-known supermodel and spokeswoman for encouraging the public to see beauty in everything. others like harlow have realized the beauty in vitiligo. jasmine colgan, an american photographer discovered she had vitiligo at age 21.3 while at first devastated, capturing body on camera, led her to conclude that her skin was a work of art. her project “tough skin,” demonstrates the mental toughness of individuals with vitiligo and highlights the unique beauty of this skin condition. colgan hopes to extend the campaign of “tough skin” to reveal the beauty of all individuals with an outer difference including albinism, cleft palate, and down syndrome.3 figure 1. photograph of winnie harlow. photograph attributed to georges biard [cc by-sa 4.0 (https://creativecommons.org/licenses/by-sa/4.0)], from wikimedia commons. vitiligo is a condition that is very difficult to treat. some patients disguise their appearance with self-tanning lotions or cosmetic camouflage. others may decide to accept the natural history of this condition treatment. harlow and colgan have not only learned to live with vitiligo, they have embraced their skin’s unique look. dermatologists should be open to receiving the message that treatment to correct this skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 440 condition is not the only option available to patients. conflict of interest disclosures: none. funding: none. corresponding author: ashley brown mcgovern medical school university of texas health science center at houston 6431 fannin st houston, tx email: ashley.brown@uth.tmc.edu references: 1. patvekar ma, deo ks, verma s, kothari p, gupta a. quality of life in vitiligo: relationship to clinical severity and demographic data. pigment int. 2017;4:104-8 doi: 10.4103/23495847.219684 2. giles, k, davison, r. 'i think i'm beautiful': model winnie harlow, who suffers from rare vitiligo skin condition, gives empowering talk at women in the world event. dailymail. october 13, 2015. http://www.dailymail.co.uk/tvshowbi z/article-3266579/i-think-mbeautiful-model-winnie-harlowsuffers-rare-vitiligo-skin-conditiongives-empowering-talk-womenworld-event.html. accessed december 28, 2017. 3. saunders, j. ‘you gotta have tough skin’! grandmother’s dying words inspires photographer with vitiligo to embrace her look and help others. storytrender. july 5, 2017. http://www.storytrender.com/18103/ gotta-tough-skin-grandmothers-dyingwords-inspires-photographer-vitiligoembrace-look-help-others/. accessed december 28, 2017. mailto:ashley.brown@uth.tmc.edu http://www.storytrender.com/18103/gotta-tough-skin-grandmothers-dying-words-inspires-photographer-vitiligo-embrace-look-help-others/ http://www.storytrender.com/18103/gotta-tough-skin-grandmothers-dying-words-inspires-photographer-vitiligo-embrace-look-help-others/ http://www.storytrender.com/18103/gotta-tough-skin-grandmothers-dying-words-inspires-photographer-vitiligo-embrace-look-help-others/ http://www.storytrender.com/18103/gotta-tough-skin-grandmothers-dying-words-inspires-photographer-vitiligo-embrace-look-help-others/ duration of response and progression-free survival with sonidegib 200 mg once daily until disease progression or start of new antineoplastic therapy in patients with locally advanced basal cell carcinoma: results of the 42-month, randomized, double-blind bolt study michael migden,1 john lear,2 nicholas squittieri,3 li liu,3 alexander guminski,4 reinhard dummer5 1university of texas md anderson cancer center, departments of dermatology, division of internal medicine, and head and neck surgery, division of surgery, houston, tx, usa; 2manchester academic health science centre; university of manchester, manchester, uk; 3sun pharmaceutical industries, inc., princeton, nj, usa; 4royal north shore hospital, st leonards, nsw, australia; 5department of dermatology, university of zürich, skin cancer center, university hospital, zürich, switzerland background • incidence of basal cell carcinoma (bcc) is increasing worldwide by an approximate 1% annually1,2 • in cases of advanced bcc, current treatment modalities (eg, surgery) are contraindicated3,4 • hedgehog inhibitors (hhis) were developed to block aberrant hedgehog signaling found in most sporadic bccs, and inhibition of the hedgehog pathway is among the few treatment options available for patients with advanced bcc5,6 • sonidegib—an hhi that selectively targets smoothened¹—is approved in the us, the eu, switzerland, and australia for the treatment of adult patients with locally advanced bcc (labcc) not amenable to curative surgery or radiation therapy7-10 — sonidegib is also approved for the treatment of metastatic bcc (mbcc) in switzerland and australia9,10 • through 42 months of the phase 2 bolt (basal cell carcinoma outcomes with lde225 [sonidegib] treatment) trial (nct01327053), sonidegib 200 mg/day demonstrated durable efficacy and consistent/manageable toxicity11-15 objectives • here, we report duration of response (dor) and progression-free survival (pfs), with start of new antineoplastic therapy considered progressive disease (pd), in aggressive and nonaggressive labcc in a sensitivity analysis from the bolt 42-month results methods • bolt was a randomized, double-blind, phase 2 clinical trial conducted in 58 centers across 12 countries11 (figure 1) figure 1. bolt study design apatients previously treated with sonidegib or other hhi were excluded; bstratification was based on stage, disease histology for patients with labcc (nonaggressive vs aggressive), and geographic region; ctreatment was continued until disease progression, unacceptable toxicity, death, study termination, or withdrawal of consent. ae, adverse event; bolt, basal cell carcinoma outcomes with lde225 (sonidegib) treatment; cr, complete response; dor, duration of response; hhi, hedgehog inhibitor; labcc, locally advanced basal cell carcinoma; mbcc, metastatic basal cell carcinoma; mrecist, modified response evaluation criteria in solid tumors; orr, objective response rate; os, overall survival; pfs, progression-free survival; q8w, every 8 weeks; q12w, every 12 weeks; ttr, time to tumor response. • eligible patients had either histologically confirmed labcc (not amenable to curative surgery or radiation) or mbcc (for which all other treatment options had been exhausted) • primary and secondary endpoints are summarized in figure 2 presented at fall clinical dermatology conference for pas & nps 2020, april 3–5, orlando, fl, usa follow-up (after treatment discontinuation) • tumor response q8w during year 1 and then q12w until progression • subsequent anticancer therapy • aes until 30 days after last dose of sonidegib • survival followup q12w until death, lost to follow-up, or withdrawn consent (and at time of final analysis) endpoints primary: orr (central review) by mrecist (labcc) or recist v1.1 (mbcc) key secondary: dor, cr (central review) other secondary: orr, dor (investigator review); pfs, ttr (central and investigator review); os, safety stratificationb randomization (1:2) sonidegib 200 mg/dc sonidegib 800 mg/dc patient populationa • labcc (aggressive and nonaggressive) • mbcc figure 2. bolt study endpoints bolt, basal cell carcinoma outcomes with lde225 (sonidegib) treatment; cr, complete response; dor, duration of response; labcc, locally advanced basal cell carcinoma; mbcc, metastatic basal cell carcinoma; mrecist, modified response evaluation criteria in solid tumors; orr, objective response rate; os, overall survival; pfs, progression-free survival; pr, partial response; ttr, time to tumor response. • tumor response was evaluated by central review using modified response evaluation criteria in solid tumors (mrecist) for patients with labcc (figure 2 and 3) — includes assessment by magnetic resonance imaging complemented by color photography and histology of multiple biopsy samples; complete response was defined as negative histology with complete disappearance of target lesions by all image modalities11,14 figure 3. tumor evaluation per mrecist (labcc) bcc-mrecist is a composite multimodal evaluation used to integrate mri according to recist v1.1,16 standard and annotated color photography using bidimensional who criteria,17 and histology in multiple biopsies based on lesion surface area in the complex setting of posttreatment scarring, fibrosis, and ill-defined lesion borders. complete response is defined as a negative mri, negative photo, and negative histology. partial response is defined as ≥50% reduction in bidimensional format. bcc, basal cell carcinoma; labcc, locally advanced bcc; mrecist, modified response evaluation criteria in solid tumors; mri, magnetic resonance imaging; who, world health organization. • tumor evaluations were to be continued per the study evaluation schedule (once every 8 weeks during the first year and once every 12 weeks thereafter) following discontinuation of study treatment prior to documented pd for any reason other than withdrawal of consent or death — evaluations were performed until pd was determined per central review, the start of a new antineoplastic therapy, or loss to follow-up — new antineoplastic therapy was defined as any additional (secondary) anticancer therapy or surgery — for analysis by tumor histology, aggressive histological subtypes included micronodular, infiltrative, multifocal, basosquamous, and sclerosing; nonaggressive histological subtypes included nodular and superficial • safety and tolerability were assessed through monitoring and recording adverse events (aes); regular monitoring of hematology, clinical chemistry, and electrocardiograms; and routine monitoring of vital signs and physical condition — aes were coded using medical dictionary for regulatory activities (v19.0) terminology, and toxicity was assessed according to the national cancer institute common terminology criteria for adverse events (v4.03)18 primary orr → best overall confirmed response of cr or pr per central review according to mrecist (labcc) or recist v1.1 (mbcc) key secondary dor and cr rates per central review according to mrecist (labcc) or recist v1.1 (mbcc) other secondary • os • safety • orr and dor per investigator review • pfs and ttr per central and investigator review composite overall response per bcc-mrecist mri per recist v1.1 photo per who criteria+ histology+ results • at baseline, 58% of patients with labcc (n = 66) receiving sonidegib 200 mg/day were male, and the median age was 67 years (table 1) • more patients had an aggressive histologic subtype (56%) than a nonaggressive histologic subtype (44%) table 1. baseline demographics and disease characteristics in patients with labcc receiving sonidegib 200 mg daily labcc (n = 66) median age (range), years 67 (25–92) male 38 (57.6) ecog performance status 0 44 (66.7) 1 16 (24.2) 2 4 (6.1) unknown 2 (3.0) labcc histologic subtype aggressivea 37 (56.1) nonaggressiveb 29 (43.9) number of lesions in patients with labcc 1 30 (45.5) ≥2 36 (54.5) prior antineoplastic therapy for labcc surgery 48 (72.7) radiotherapy 12 (18.2) data presented as n (%) unless otherwise indicated. aincludes micronodular, infiltrative, multifocal, basosquamous, and sclerosing histological subtypes; bincludes nodular and superficial histological subtypes. ecog, eastern cooperative oncology group; labcc, locally advanced basal cell carcinoma. • at 42 months, the objective response rate (95% confidence interval [ci]) in patients with labcc was 56.1% (43.3%–68.3%) (table 2) table 2. efficacy outcomes per central review in patients with labcc receiving sonidegib 200 mg daily labcc (n = 66) orr, % (95% ci) 56.1 (43.3, 68.3) cr, % (95% ci) 4.5 (0.9, 12.7) dcr, % 90.9 dor, median, months (95% ci) 26.1 (ne) pfs, median, months (95% ci) 22.1 (ne) ttr, median, months (95% ci) 4.0 (3.8, 5.6) bcc, basal cell carcinoma; ci, confidence interval; cr, complete response; dcr, disease control rate; dor, duration of response; labcc, locally advanced bcc; ne, not estimable; orr, objective response rate; pfs, progression-free survival; ttr, time to tumor response. • best overall response by central review was similar between patients with aggressive and nonaggressive histology (figure 4) figure 4. best overall response by central review using mrecist aggressive includes micronodular, infiltrative, multifocal, basosquamous, and sclerosing histological subtypes; nonaggressive includes nodular and superficial histological subtypes. mrecist, modified response evaluation criteria in solid tumors. outcomes in patients starting new antineoplastic therapy • median dor (95% ci) per central review in all labcc patients (n = 66) was 13.0 (not estimable [ne]) months and median pfs (95% ci) was 19.0 (14.0–30.7) months • median dor (95% ci) in patients starting new antineoplastic therapy with aggressive (n = 37) labcc was 13.0 (7.4–35.7) months and ne for patients with nonaggressive (n = 29) labcc; median pfs (95% ci) in patients starting new antineoplastic therapy with aggressive and nonaggressive labcc was 14.9 (13.2–30.7) and 22.1 (ne) months, respectively • dor 12-month event-free probability percent estimate with labcc, aggressive labcc, and nonaggressive labcc was 63.2%, 54.6%, and 75.0%, respectively (table 3) table 3. duration of response and progression-free survival per central review in labcc patients with new antineoplastic therapy all labcc patients (n = 66) aggressive histology (n = 37) nonaggressive histology (n = 29) dor n/n (%) 15/37 (40.5) 10/22 (45.5) 5/15 (33.3) pd, n (%) 15 (40.5) 10 (45.5) 5 (33.3) median (95% ci) 13.0 (ne) 13.0 (7.4–35.7) ne % event-free probability estimate (95% ci) 6 months 86.8 (68.5–94.8) 83.6 (57.3–94.4) 91.7 (53.9–98.8) 9 months 72.5 (52.4–85.3) 71.6 (44.6–87.1) 75.0 (40.8–91.2) 12 months 63.2 (41.7–78.6) 54.6 (26.2–76.1) 75.0 (40.8–91.2) pfs n/n (%) 23/66 (34.8) 16/37 (43.2) 7/29 (24.1) pd, n (%) 23 (34.8) 16 (43.2) 7 (24.1) median (95% ci) 19.0 (14.0–30.7) 14.9 (13.2–30.7) 22.1 (ne) % event-free probability estimate (95% ci) 6 months 93.0 (82.4–97.3) 88.3 (71.7–95.4) 100 (ne) 9 months 90.9 (79.5–96.1) 88.3 (71.7–95.4) 94.7 (68.1–99.2) 12 months 80.8 (65.9–89.7) 80.1 (60.3–90.7) 81.6 (52.8–93.7) the start of any anticancer therapy different from sonidegib is considered disease progression. ci, confidence interval; dor, duration of response; labcc, locally advanced basal cell carcinoma; n, total number of events included in the analysis (an event is disease progression or death due to any cause); n, total number of patients included in the analysis; ne, not estimable; pd, progressive disease; pfs, progression-free survival. 5.4 3.4 54.1 48.3 32.4 37.9 2.7 0 100 80 60 40 20 0 p er ce nt o f p at ie nt s complete response partial response stable disease progressive disease safety and tolerability • overall, the safety profile of sonidegib 200 mg/day was manageable and consistent with prior analyses11,13 • the majority of aes were grade 1–2 in severity • the most common all-grade aes in patients receiving sonidegib 200 mg/day were muscle spasms (54.4%), alopecia (49.4%), and dysgeusia (44.3%) (figure 5) figure 5. adverse events reported in ≥20% of patients receiving sonidegib 200 mg daily ck, creatine kinase. conclusions • patients with labcc receiving sonidegib 200 mg/day experienced durable tumor response until disease progression or start of new antineoplastic therapy • safety and tolerability of sonidegib 200 mg/day at 42 months was consistent with earlier data references 1) xiang f, et al. jama dermatol. 2014; 150:1063–71; 2) asgari mm, et al. jama dermatol. 2015; 151:976–81; 3) amici jm, et al. eur j dermatol. 2015; 25:586–94; 4) lear jt, et al. br j cancer. 2014; 111:1476–81; 5) cortes je, et al. cancer treat rev. 2019; 76:41–50; 6) kim jys, et al. j am acad dermatol. 2018; 78:540–59; 7) odomzo (sonidegib) [package insert]. cranbury, nj: sun pharmaceutical industries, inc.; 2017; 8) european medicines agency. summary of product characteristics, wc500188762; 9) swissmedic, authorization number 65065, 2015; 10) australian government department of health, artg 292262; 11) migden mr, et al. lancet oncol. 2015; 16:716–28; 12) migden mr, et al. j clin oncol. 2018; 36:suppl abstr 9551; 13) lear jt, et al. j eur acad dermatol venereol. 2018; 32:372–81; 14) dummer r, et al. j am acad dermatol. 2016; 75:113–25.e115; 15) dummer r, et al. br j dermatol. 2019; 10.1111/bjd.18552; 16) eisenhauer ea, et al. eur j cancer. 2009; 45 (2): 228–47; 17) world health organization. http://whqlibdoc. who.int/offset/who_offset_48.pdf; 18) national cancer institute. https://evs.nci.nih.gov/ftp1/ctcae/ctcae_4.03/archive/ctcae_4.0_2009-05-29_ quickreference_8.5x11.pdf. acknowledgments medical writing and editorial support were provided by zehra gundogan, vmd, and jennifer meyering, rn, ms, cmpp, of alphabiocom, llc, and funded by sun pharmaceutical industries, inc. disclosures mm has participated on advisory boards and received honoraria from genentech; novartis pharmaceuticals corporation; sun pharmaceutical industries, inc.; and regeneron pharmaceuticals. jl has received personal fees from novartis pharmaceuticals corporation. ll and ns are employees of sun pharmaceutical industries, inc. ag has participated on advisory boards for bristol-myers squibb, pfizer, and sanofi; received honoraria from novartis pharmaceuticals corporation; and received travel support from astellas and bristol-myers squibb. rd has received grants and personal fees from bristolmyers squibb; glaxosmithkline; merck sharpe and dohme; novartis pharmaceuticals corporation; roche; and sun pharmaceutical industries, inc. aggressive (n = 37) nonaggressive (n = 29) 0 20 40 60 decreased appetite ck increased weight decreased diarrhea fatigue nausea dysgeusia alopecia muscle spasm percent of patients grade 3-4 grade 1-2 51.9 49.4 44.3 38.0 31.6 30.4 25.3 24.1 21.5 54.4 49.4 44.3 39.2 32.9 31.6 30.4 30.4 22.8 skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 840 brief article a case of a large, painful dermatofibrosarcoma protuberans arising from a traumatic scar daniel l. fischer, do, ma1, graham litchman, do, ms1 1st. john’s episcopal hospital, far, rockaway, ny dermatofibrosarcoma protuberans (dfsp) is a rare, locally aggressive and seldom metastatic soft tissue tumor usually confined to the dermis and subcutaneous tissues.1 the first case of dfsp was described in 1924 and termed by hoffman in 1925.2 it accounts for less than 0.1% of all malignant neoplasms and 1% of soft tissue sarcomas.3 diagnosis requires skin biopsy with histochemical analysis and mainstay of treatment is surgery. it is most commonly seen among adults in their thirties, with a predominance in blacks.4 most lesions are no more than 5 cm in diameter and occur spontaneously.5 here we describe a case of dfsp that arose within a preexisting scar and grew to much larger proportions than what is typically observed. our case involves a 35-year-old caucasian man who presented to the emergency department for 10/10 sharp, squeezing chest pain originating at the site of a left chest mass. the mass had formed out of an area of scar tissue that had developed after a traumatic motor vehicle accident. however, the tissue had formed a mass and grew exponentially over the past two months (figure 1). during this time the mass became increasingly painful causing intermittent episodes of stabbing pain, radiating to the back, lasting about 20 seconds, and recurring throughout the day. the patient had not sought medical help during this time due to lack of insurance. physical examination was remarkable for a large, multilobulated, highly vascular chest wall mass localized to the left sternal border measuring approximately 10 by 12 centimeters (cm) with well-demarcated margins. the lower portion of the mass was firm to palpation while the upper portion was abstract here we report a case of a patient with dermatofibrosarcoma protuberans (dfsp) that presented originally to the emergency department with chief complaint of ‘chest pain arising from a chest wall mass’. this case is unique for multiple reasons including the fact that the dfsp caused this patient severe pain that radiated from the site of the mass to the patient’s back. the lesion originated from a traumatic scar that the patient had obtained following a car accident two years prior to presentation. in addition, the dfsp was significantly larger in size than what has typically been reported in the literature. this case illustrates that dfsp has the potential to present with multiple atypical features. introduction case report https://paperpile.com/c/m1svg8/wojf https://paperpile.com/c/m1svg8/uilo https://paperpile.com/c/m1svg8/9mzv https://paperpile.com/c/m1svg8/yvay https://paperpile.com/c/m1svg8/lgj5 skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 841 soft. the mass was also highly sensitive to touch. the differential diagnosis included arteriovenous malformation, soft tissue hemangioma, and soft tissue sarcoma. figure 1. a large, highly vascular left-sided chest wall mass measuring 10 by 12 centimeters that was identified to be a dfsp on histology. ct chest revealed an 11.3 by 8.8 by 6.3 cm left anterior chest wall mass located in the subcutaneous tissue with no evidence of muscle or bony invasion. mri chest revealed multiple well-circumscribed, grape-like hypervascular masses in the subcutaneous soft tissue of the left anterior chest wall. there was predominant vascular supply from the intercostal and internal mammary chain vascular structures. no evidence of chest wall invasion was appreciated. ultrasound-guided core needle biopsy showed a relatively monotonous spindle cell proliferation with storiform architecture throughout. immunohistochemistry showed positivity for cd34 and vimentin, and negative for s100, desmin, ema, and cd68. ki67 index was brisk and stat-6 and factor xiii were negative. the interpretation was read as spindle cell neoplasm of intermediate grade favoring dfsp. dermatofibrosarcoma protuberans typically presents as a slow growing, nontender plaque that with time develops an asymmetric and multinodular, red, yellow, or brown appearance.1 dfsp most commonly appears on the trunk or extremities and less often on the head and neck but can appear almost anywhere.3 local recurrence following excision is fairly common.4 with treatment, the prognosis is excellent (10-year survival rate of 99.1%).4 dfsps are typically asymptomatic which makes this case particularly unique as our patient was symptomatic with severe pain at the site of the lesion, and the prime reason for him seeking medical attention. the cause of dfsp is not known but prior studies suggest that translocations between chromosomes 17 and 22 may play a role in their development. this translocation is thought to cause an upregulation of the platelet-derived growth factor beta polypeptide gene leading to cellular proliferation.6 according to several studies, it is estimated that up to 10-20% of dfsp have arisen from prior trauma.7-9 this was the case in our patient, as his malignancy had arisen from a scar that he had acquired after a motor vehicle injury two years prior to his presentation at our hospital. diagnosis of dfsp is confirmed via incisional or excisional biopsy. this can often be challenging if the lesion is highly vascular, as in our case. in this scenario, an mri of the lesion was done to map the vascular regions and define tumor extension. this was followed by a core-needle biopsy without complication. examination of hematoxylin discussion https://paperpile.com/c/m1svg8/wojf https://paperpile.com/c/m1svg8/9mzv https://paperpile.com/c/m1svg8/yvay https://paperpile.com/c/m1svg8/yvay https://paperpile.com/c/m1svg8/5si4 https://paperpile.com/c/m1svg8/us0y skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 842 and eosin-stained specimens by light microscopy yields the diagnosis.1 pathology typically reveals monotonous spindle cell proliferation with storiform architecture throughout with positivity for cd34 and vimentin and negative staining for factor xiii, s-100, cd68, and 5% positivity for ki67.10 this correlated with the histopathology findings in our patient. when the diagnosis of a large dfsp is suspect, a multidisciplinary approach is recommended with tertiary center evaluation. the standard treatment for dfsp is surgical removal with mohs micrographic surgery (mms). this method is preferred over wide excision as it ensures complete removal of tumor margins and is appropriate in cases like dfsp in which the depth of extension is highly unpredictable. it also reduces the likelihood of tumor recurrence (1% with mms; 7.3% with wide excision). in the rare scenario that dfsp has metastasized or is unresectable, chemotherapy with imatinib mesylate or radiation therapy may be used.2 close follow up is required post-treatment and evaluation ideally every 3-6 months due to the high recurrence rate of dfsp. our patient was scheduled for treatment by mms at a specialized surgical institute. although dfsp is a rare disease with definitive treatment and good prognosis, its high rate of misdiagnosis and potential for delay in management can lead to poorer outcomes and more complex treatment. it is important for primary care physicians, dermatologists, surgeons, and pathologists to be clinically suspicious of this tumor and its variations in presentation in order to diagnosis and treat early. post-operative management is critical, as these lesions have a high rate of recurrence. thus, physicians should pay close attention to patient history of prior dfsp and changing appearance of scar tissue in their clinical evaluation. conflict of interest disclosures: none funding: none corresponding author: daniel fischer, do, ma st. john’s episcopal hospital far rockaway, ny email: drdeefish@gmail.com references: 1. wu s, huang y, li z, wu h, li h. collagen features of dermatofibrosarcoma protuberans skin base on multiphoton microscopy. technol cancer res treat. 2018;17:1533033818796775. 2. angouridakis n, kafas p, jerjes w, et al. dermatofibrosarcoma protuberans with fibrosarcomatous transformation of the head and neck. head neck oncol. 2011;3:5. 3. harati k, lange k, goertz o, et al. a singleinstitutional review of 68 patients with dermatofibrosarcoma protuberans: wide reexcision after inadequate previous surgery results in a high rate of local control. world j surg oncol. 2017;15(1):5. 4. kreicher kl, kurlander de, gittleman hr, barnholtz-sloan js, bordeaux js. incidence and survival of primary dermatofibrosarcoma protuberans in the united states. dermatol surg. 2016;42 suppl 1:s24-s31. 5. archontaki m, korkolis dp, arnogiannaki n, et al. dermatofibrosarcoma protuberans: a case series of 16 patients treated in a single institution with literature review. anticancer res. 2010;30(9):3775-3779. 6. lemm d, mügge lo, mentzel t, höffken k. current treatment options in dermatofibrosarcoma protuberans. j cancer res clin oncol. 2009;135(5):653-665. 7. de araujo rn, marcarini r, ferreira bdfm, obadia dl. dermatofibrosarcoma protuberans rapid growth after incisional biopsy. medicina cutánea ibero-latinoamericana. 2017;45(1):41-44. 8. tanaka a, hatoko m, tada h, kuwahara m, iioka h, niitsuma k. dermatofibrosarcoma protuberans arising from a burn scar of the axilla. ann plast surg. 2004;52(4):423-425. conclusion https://paperpile.com/c/m1svg8/wojf https://paperpile.com/c/m1svg8/tl31 https://paperpile.com/c/m1svg8/uilo http://paperpile.com/b/m1svg8/wojf http://paperpile.com/b/m1svg8/wojf http://paperpile.com/b/m1svg8/wojf http://paperpile.com/b/m1svg8/wojf http://paperpile.com/b/m1svg8/wojf http://paperpile.com/b/m1svg8/wojf http://paperpile.com/b/m1svg8/wojf http://paperpile.com/b/m1svg8/uilo http://paperpile.com/b/m1svg8/uilo http://paperpile.com/b/m1svg8/uilo http://paperpile.com/b/m1svg8/uilo http://paperpile.com/b/m1svg8/uilo http://paperpile.com/b/m1svg8/uilo http://paperpile.com/b/m1svg8/9mzv http://paperpile.com/b/m1svg8/9mzv http://paperpile.com/b/m1svg8/9mzv http://paperpile.com/b/m1svg8/9mzv http://paperpile.com/b/m1svg8/9mzv http://paperpile.com/b/m1svg8/9mzv http://paperpile.com/b/m1svg8/9mzv http://paperpile.com/b/m1svg8/9mzv http://paperpile.com/b/m1svg8/yvay http://paperpile.com/b/m1svg8/yvay http://paperpile.com/b/m1svg8/yvay http://paperpile.com/b/m1svg8/yvay http://paperpile.com/b/m1svg8/yvay http://paperpile.com/b/m1svg8/yvay http://paperpile.com/b/m1svg8/yvay http://paperpile.com/b/m1svg8/yvay http://paperpile.com/b/m1svg8/lgj5 http://paperpile.com/b/m1svg8/lgj5 http://paperpile.com/b/m1svg8/lgj5 http://paperpile.com/b/m1svg8/lgj5 http://paperpile.com/b/m1svg8/lgj5 http://paperpile.com/b/m1svg8/lgj5 http://paperpile.com/b/m1svg8/lgj5 http://paperpile.com/b/m1svg8/5si4 http://paperpile.com/b/m1svg8/5si4 http://paperpile.com/b/m1svg8/5si4 http://paperpile.com/b/m1svg8/5si4 http://paperpile.com/b/m1svg8/5si4 http://paperpile.com/b/m1svg8/5si4 http://paperpile.com/b/m1svg8/us0y http://paperpile.com/b/m1svg8/us0y http://paperpile.com/b/m1svg8/us0y http://paperpile.com/b/m1svg8/us0y http://paperpile.com/b/m1svg8/us0y http://paperpile.com/b/m1svg8/us0y http://paperpile.com/b/m1svg8/us0y http://paperpile.com/b/m1svg8/8yfm http://paperpile.com/b/m1svg8/8yfm http://paperpile.com/b/m1svg8/8yfm http://paperpile.com/b/m1svg8/8yfm http://paperpile.com/b/m1svg8/8yfm http://paperpile.com/b/m1svg8/8yfm skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 843 9. saeki h, kadono t, le pavoux a, mori e, tamaki k. dermatofibrosarcoma protuberans with col1a1-pdgfb fusion transcript arising on a scar due to a previous drainage tube insertion. j dermatol. 2008;35(10):686688. 10. yang h, yu l. cutaneous and superficial soft tissue cd34+ spindle cell proliferation. arch pathol lab med. 2017;141(8):10921100. http://paperpile.com/b/m1svg8/qbjw http://paperpile.com/b/m1svg8/qbjw http://paperpile.com/b/m1svg8/qbjw http://paperpile.com/b/m1svg8/qbjw http://paperpile.com/b/m1svg8/qbjw http://paperpile.com/b/m1svg8/qbjw http://paperpile.com/b/m1svg8/qbjw http://paperpile.com/b/m1svg8/qbjw http://paperpile.com/b/m1svg8/tl31 http://paperpile.com/b/m1svg8/tl31 http://paperpile.com/b/m1svg8/tl31 http://paperpile.com/b/m1svg8/tl31 http://paperpile.com/b/m1svg8/tl31 boni elewski1, alan menter2, jeffrey crowley3, stephen tyring4, yang zhao5, simon lowry5, stephen rozzo5, alan mendelsohn5, jeffrey parno5, kenneth gordon6 sustained and improved efficacy of tildrakizumab from week 28 to week 52 in treating moderate-to-severe plaque psoriasis 1. department of dermatology, the university of alabama at birmingham, birmingham, alabama usa; 2. division of dermatology, baylor university medical center, dallas, tx, usa; 3. bakersfield dermatology, bakersfield, ca, usa; 4. department of dermatology, university of texas health science center, houston, tx, usa; 5. sun pharmaceutical industries, princeton, nj, usa; 6. medical college of wisconsin, milwaukee, wi, usa • psoriasis is a common, chronic, and immunemediated skin disease, affecting 3.2% of the us population. approximately 7.4 million people in the us have psoriasis1. • psoriasis is characterized by painful, pruritic, well-demarcated, erythematous plaques with silver scale1,2, and often negatively impacts patients’ overall health, quality of life, productivity, and interpersonal relationship2-4. • tildrakizumab is a high-affinity, humanized, igg1 κ, anti-interleukin–23 monoclonal antibody designed to block interleukin-23 p195. it is administered subcutaneously once every 12 weeks, after two initial doses administered 4 weeks apart5. • two phase-3, double-blind, randomized controlled trials (resurface 1: nct01722331; resurface 2: nct01729754) demonstrated efficacy and safety of tildrakizumab in the treatment of adult patients with moderate-to-severe plaque psoriasis over the first 28 weeks5. • this analysis evaluated longer-term data from these two trials to examine whether the efficacy is sustained or improved from week 28 through week 52. study design of resurface 1 • overall, 352 patients on tildrakizumab 100 mg (male: 69.9%; mean baseline age: 44.9 years) and 313 on tildrakizumab 200 mg (male: 67.1%; mean baseline age: 46.4 years) were included. • the proportions of patients achieving pasi 100, pasi 90-99, pasi 75-89 and pasi 50-74 at week 28 were 25.9%, 38.4%, 25.3%, and 10.5% respectively for those on the 100 mg dose, and 24.6%, 24.3%, 19.5%, and 31.6% respectively for those on the 200 mg dose. • week-52 pasi responses for patients treated with tildrakizumab 100 mg: − among patients achieving week-28 pasi 100 (n=91), 75.8% maintained pasi 100, 18.7% had pasi 90-99, 94.5% had pasi≥90, and all had pasi≥75 at week 52 − among patients achieving week-28 pasi 90-99 (n=135), 25.2% improved to pasi 100, 60.7% maintained pasi 90-99, and 10.4% had pasi 7589 at week 52 − among patients achieving week-28 pasi 75-89 (n=89), 6.7% improved to pasi 100, 27.0% improved to pasi 90-99, and 40.4% maintained pasi 75-89 at week 52 − among patients achieving week-28 pasi 50-74 (n=37), 18.9% improved to pasi 100, 10.8% improved to pasi 90-99, 35.1% improved to pasi 75-89, and 24.3% maintained pasi 50-74 at week 52 study design of resurface 2 • week-52 pasi responses for patients treated with tildrakizumab 200 mg: − among patients achieving week-28 pasi 100 (n=77), 84.4% maintained pasi 100, 11.7% had pasi 90-99, 96.1% had pasi≥90, and all had pasi≥75 at week 52 − among patients achieving week-28 pasi 90-99 (n=76), 32.9% improved to pasi 100, 48.7% maintained pasi 90-99, and 17.1% had pasi 7589 at week 52 − among patients achieving week-28 pasi 75-89 (n=61), 8.2% improved to pasi 100, 32.8% improved to pasi 90-99, and 39.3% maintained pasi 75-89 at week 52 − among patients achieving week-28 pasi 50-74 (n=99), 6.1% improved to pasi 100, 14.1% improved to pasi 90-99, 32.3% improved to pasi 75-89, and 41.4% maintained pasi 50-74 at week 52 • among patients who achieved week-28 pasi≥90 with either dose of tildrakizumab, 88.9-89.4% maintained pasi≥90 at week 52. • overall, 91.1% patients on the 100 mg dose and 93.9% on the 200 mg dose with week-28 pasi≥75 maintained pasi≥75 at week 52. • in addition, 33.7%-41.0% of patients with week-28 pasi 75-89 improved to pasi≥90. • among patients with week-28 pasi 50-74, 20.2-29.7% achieved pasi≥90 and 52.564.9% achieved pasi≥75 at week 52. • overall, 2.6% of patients on the 100 mg (9 out of 352) or 200 mg (8 out of 313) dose had week-52 pasi<50. baseline characteristics • among patients with moderate-to-severe psoriasis treated with tildrakizumab 100 or 200 mg at weeks 0, 4, then every 12 weeks, those who achieved week-28 pasi≥50 and continued on the same dose had sustained or improved efficacy from week 28 through week 52. • the majority patients who achieved week-28 pasi≥75 or pasi≥90 maintained pasi≥75 or pasi≥90 at week 52. • more than half of partial responders (pasi 5074) at week 28 eventually achieved pasi≥75 and at least 1 in 5 achieved pasi≥90 at week 52. introduction methods • both phase-3 trials randomized adult patients with moderate-to-severe plaque psoriasis to receive tildrakizumab 100 mg or tildrakizumab 200 mg at weeks 0, 4, then every 12 weeks, and used three-part study design − part 1 (week 0-12) randomized patients to: tildrakizumab 100 mg, tildrakizumab 200 mg, placebo, or etanercept 50mg (in resurface 2) − part 2 (week 12-28) re-randomized placebo patients to tildrakizumab; − part 3 (week 28-64, resurface 1; week 28-52, resurface 2) re-randomized patients with psoriasis area and severity index (pasi) response ≥50% to the same, a higher or a lower dose of tildrakizumab, or placebo based on their week-28 pasi responses • this analysis included only patients treated with the same dose of tildrakizumab (100 mg or 200 mg) throughout the first 52 weeks. • four mutually exclusive groups were created based on patients’ week-28 pasi response: pasi 100, pasi 90-99, pasi 75-89 and pasi 50-74. • baseline characteristics and pasi responses at week 52 (observed data) were analyzed for each week-28 pasi-response group. results conclusions references 1. rachakonda td, schupp cw, armstrong aw. psoriasis prevalence among adults in the united states. j am acad dermatol. 2014;70(3):512-516. 2. menter a, gottlieb a, feldman sr, et al. guidelines of care for the management of psoriasis and psoriatic arthritis: section 1. overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics. j am acad dermatol. 2008;58(5):826-850. 3. pariser d, schenkel b, carter c, et al. a multicenter, non-interventional study to evaluate patient-reported experiences of living with psoriasis. j dermatolog treat. 2016;27(1):1926. 4. vanderpuye-orgle j, zhao y, lu j, et al. evaluating the economic burden of psoriasis in the united states. j am acad dermatol. 2015;72(6):961-967 e965. 5. reich k, papp ka, blauvelt a, et al. tildrakizumab versus placebo or etanercept for chronic plaque psoriasis (resurface 1 and resurface 2): results from two randomised controlled, phase 3 trials. lancet. 2017;390(10091):276-288. acknowledgments dr. peter sun from kailo research group provided writing support on this poster, with funding from sun pharmaceutical industries. disclosures drs. elewski, menter, crowley, tyring and gordon were investigators of the two phase-3 clinical trials for tildrakizumab (resurface 1 and resurface 2). drs. zhao, lowry, rozzo and mendelsohn and mr. parno are employees of sun pharmaceutical industries. week-28 pasi categories 100 90-99 75-89 50-74 ≥50 tildrakizumab 100 mg cohort number of patients 91 135 89 37 352 mean age (year, sd) 42.6 (14.1) 45.0 (13.1) 46.1 (13.1) 47.2 (13.8) 44.9 (13.5) proportion of males (%) 69.2% 70.4% 66.3% 78.4% 69.9% race (%) white 80.2% 86.7% 85.4% 70.3% 83.0% black 3.3% 1.5% 3.4% 0.0% 2.3% asian 6.6% 9.6% 9.0% 27.0% 10.5% others 9.9% 2.2% 2.2% 2.7% 4.2% weight (kg): mean (sd) 83.0 (18.8) 87.4 (21.6) 94.5 (23.6) 83.4 (22.4) 87.6 (21.9) bmi3 (kg/m2): mean (sd) 28.1 ( 5.7) 29.2 ( 6.7) 31.9 ( 7.7) 28.4 ( 7.1) 29.5 ( 6.9) body surface area: % (sd) 28.9 (16.1) 33.5 (18.6) 32.0 (16.6) 35.7 (19.9) 32.2 (17.7) disease duration: years (sd) 14.3 (10.9) 16.8 (11.1) 17.8 (12.8) 14.3 (10.4) 16.2 (11.5) pasi: mean (sd) 18.5 ( 5.8) 20.9 ( 7.9) 19.6 ( 6.6) 20.6 ( 8.5) 19.9 ( 7.2) previous medical conditions (%) psoriatic arthritis 17.6% 16.3% 15.7% 18.9% 16.8% cardiovascular diseases 25.3% 18.5% 29.2% 29.7% 24.1% diabetes 8.8% 6.7% 7.9% 10.8% 8.0% hypercholesterolemia 7.7% 5.2% 4.5% 8.1% 6.0% hyperlipidemia 12.1% 4.4% 3.4% 8.1% 6.5% hypertension 24.2% 18.5% 29.2% 27.0% 23.6% obesity 1.1% 6.7% 7.9% 10.8% 6.0% previously treated with biologics 12.1% 19.3% 13.5% 10.8% 15.1% tildrakizumab 200 mg cohort number of patients 77 76 61 99 313 mean age (year, sd) 45.8 (13.5) 45.4 (14.1) 47.8 (12.7) 46.9 (13.0) 46.4 (13.3) proportion of males (%) 74.0% 69.7% 54.1% 67.7% 67.1% race (%) white 81.8% 85.5% 68.9% 76.8% 78.6% black 0.0% 2.6% 4.9% 2.0% 2.2% asian 14.3% 10.5% 19.7% 21.2% 16.6% others 3.9% 1.4% 6.5% 0.0% 2.6% weight (kg): mean (sd) 86.1 (24.5) 89.5 (22.5) 87.3 (19.0) 90.2 (24.4) 88.4 (23.0) bmi3 (kg/m2): mean (sd) 28.7 ( 7.5) 30.7 ( 8.9) 31.1 ( 7.5) 30.1 ( 6.7) 30.1 ( 7.6) body surface area: % (sd) 30.8 (17.5) 29.6 (15.3) 31.7 (17.5) 33.2 (19.6) 31.4 (17.6) disease duration: years (sd) 16.8 (13.1) 17.9 (13.5) 18.7 (13.3) 17.6 (11.6) 17.7 (12.8) pasi: mean (sd) 20.7 ( 9.3) 19.7 ( 6.5) 20.1 ( 7.2) 20.1 ( 8.8) 20.1 ( 8.1) previous medical conditions (%) psoriatic arthritis 14.3% 17.1% 9.8% 22.2% 16.6% cardiovascular diseases 24.7% 30.3% 32.8% 30.3% 29.4% diabetes 9.1% 13.2% 11.5% 14.1% 12.1% hypercholesterolemia 5.2% 5.3% 6.6% 5.1% 5.4% hyperlipidemia 3.9% 6.6% 4.9% 8.1% 6.1% hypertension 24.7% 29.0% 32.8% 30.3% 29.1% obesity 2.6% 7.9% 9.8% 8.1% 7.0% previously treated with biologics 18.2% 17.1% 19.7% 17.2% 17.9% 75.8% 25.2% 6.7% 18.9% 45.6% 34.6% 33.0% 18.7% 60.7% 27.0% 10.8% 43.8% 39.0% 36.1% 5.5% 10.4% 40.4% 35.1% 8.4% 17.5% 19.3% 3.7% 20.2% 24.3% 2.2% 7.3% 9.1% 5.6% 10.8% 1.6% 2.6% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% pasi 100 (n=91) pasi 90-99 (n=135) pasi 75-89 (n=89) pasi 50-74 (n=37) pasi ≥90 (n=226) pasi ≥75 (n=315) pasi ≥50 (n=352) pasi 100 pasi 90-99 pasi 75-89 pasi 50-74 pasi <50 w e e k -5 2 p a s i r e sp o n se ( % ) week-28 pasi groups 84.4% 32.9% 8.2% 6.1% 58.8% 44.4% 32.3% 11.7% 48.7% 32.8% 14.1% 30.1% 30.8% 25.6% 3.9% 17.1% 39.3% 32.3% 10.5% 18.7% 23.0% 1.3% 16.4% 41.4% 0.7% 5.1% 16.6% 3.3% 6.1% 0.9% 2.6% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% pasi 100 (n=77) pasi 90-99 (n=76) pasi 75-89 (n=61) pasi 50-74 (n=99) pasi ≥90 (n=153) pasi ≥75 (n=214) pasi ≥50 (n=313) pasi 100 pasi 90-99 pasi 75-89 pasi 50-74 pasi <50 w e e k -5 2 p a s i r e sp o n se ( % ) week-28 pasi groups week-52 pasi responses by week-28 pasi categories: tildrakizumab 100 mg week-52 pasi responses by week-28 pasi categories: tildrakizumab 200 mg notes: pasi= psoriasis area and severity index; sd=standard deviation; bmi=body mass index skin january 2019 volume 3 issue 1 copyright 2018 the national society for cutaneous medicine 35 brief articles sweet syndrome following gynecologic surgery: pelvic abscess as a cause matthew a cornacchia, bs,1 david munger, do,2 vaagn andikyan, md,3 charles l halasz, md,4 1ross university school of medicine, miramar, fl 2department of radiology, norwalk hospital, norwalk, ct 3university of vermont, western connecticut health network, vt 4department of dermatology, columbia university, new york, ny sweet syndrome (ss), also known as acute febrile neutrophilic dermatosis, is characterized by the sudden onset of tender, erythematous cutaneous lesions (papules, nodules and plaques) accompanied by fever and leukocytosis. extracutaneous manifestations may involve the eyes, internal organs, or the musculoskeletal system. ss may be associated with infection, malignancy or autoimmune disorders. various drugs have also been implicated in this disorder.1 a dense neutrophilic infiltrate in the absence of vasculitis is characteristically present in the upper dermis.2 we describe a unique case of a patient who developed ss following pelvic abscess formation subsequent to gynecologic surgery. a 54-year-old woman presented to her dermatologist six-weeks post-operatively after undergoing robotic hysterectomy, bilateral salpingo-oophorectomy and pelvic lymph node dissection for endometrial cancer. she had a three-day history of a burning, papulovesicular rash on her extremities. she also mentioned vague lower abdominal discomfort and right hip pain that developed two-weeks following her hysterectomy. she was afebrile upon presentation. erythematous papules were noted on her extremities and trunk, with the largest lesions present on her knuckles and heels (figure 1). mucous membrane involvement was limited to one erosion on her soft palate with no conjunctival or genital lesions noted. sweet syndrome (acute febrile neutrophilic dermatosis) is characterized by painful, erythematous skin lesions clinically, and a dense infiltrate of neutrophils in the upper and middermis on histopathology. it may be associated with infection, particularly of the respiratory or gastrointestinal tract. we describe a case of sweet syndrome in a 54-year-old woman provoked by a post-surgical pelvic infection. abstract introduction case report skin january 2019 volume 3 issue 1 copyright 2018 the national society for cutaneous medicine 36 figure 1: erythematous papulovesicular lesions of sweet syndrome on the patient’s lower extremities. punch biopsies taken for hematoxylin-eosin staining and direct immunofluorescence were taken from her right arm and revealed a dense neutrophilic infiltrate in the dermis with focal papillary dermal edema, consistent with ss (figure 2). laboratory analysis was significant for an elevated alkaline phosphatase level of 179 u/l (reference range, 33-130 u/l), alanine transaminase level of a 65 u/l (reference range, 6-29 u/l), aspartate transaminase level of 60 u/l (reference range, 10-35 u/l), a white blood cell (wbc) count of 6300 µ/l (78.4% neutrophils), and a platelet count of 363 x 103/µl. additional laboratory findings included an erythrocyte sedimentation rate of 113 mm/h (reference range, <30 mm/h), creactive protein of 26.62 mg/dl (reference range, <0.80 mg/dl), and elevated antistreptolysin o titer of 299 iu/ml. anaplasma and ehrlichia titers were negative. three days later the patient returned with a low-grade fever and worsening of her cutaneous symptoms. she noted arthralgias in her fingers and no myalgias. her skin lesions were now painful and spreading more diffusely, involving her tongue, nose, buttock and feet. she was started on prednisone 40 mg/day, tapered every 5 days by 10 mg to which her skin lesions responded well. however, her abdominal pain progressively worsened and a ct of the abdomen and pelvis with iv contrast demonstrated a large 7.6 x 4.5 x 8 cm complex multiloculated, rimenhancing fluid collection along the right pelvic sidewall, highly suggestive of a postsurgical abscess (figure 3). figure 2: dense neutrophilic infiltrate in the dermis with focal papillary dermal edema, consistent with sweet’s syndrome. under ct guidance, a drainage catheter was placed and 20 cc of purulent material was aspirated. gram stain of the pelvic abscess drainage showed gram positive cocci in chains. culture of the same fluid grew out abundant group c beta hemolytic streptococci, and no anaerobes. she was admitted to the hospital for treatment with intravenous ceftriaxone and metronidazole. figure 3: ct of the abdomen & pelvis with intravenous contrast, coronal view, showing a right iliopsoas abscess with displacement of the external iliac vasculature. skin january 2019 volume 3 issue 1 copyright 2018 the national society for cutaneous medicine 37 the patient was discharged five days later with a peripherally inserted central catheter for continued administration of antibiotics for an additional four weeks. she was also instructed to continue her prednisone taper for which she had eight days remaining. the patient’s cutaneous lesions and discomfort improved dramatically and she attained complete resolution over the course of two weeks. diagnostic criteria for ss were last revised in 1994 by von den driesch.3 to accurately diagnose ss, the patient must satisfy two major criteria: abrupt onset of tender erythematous nodules or plaques and histopathological evidence of a neutrophilic infiltrate without evidence of vasculitis. additionally, the presence of two of four minor criteria is required. the minor criteria includes: 1) pyrexia over 38°c; 2) association with malignancy, inflammatory disease or preceded by an upper respiratory of gastrointestinal infection or vaccination; 3) excellent response to systemic corticosteroids or potassium iodide; and 4) laboratory values demonstrating erythrocyte sedimentation rate >20 mm/hr, positive creactive protein, >8,000 leukocytes or >70% neutrophils.3 our patient fulfilled both major criteria and the latter 2 minor criteria for a diagnosis of ss. literature suggests that hypersensitivity reactions may be responsible for ss, given its association with malignancy, drugs, autoimmune diseases and infections.2 our patient was not on any ss-inducing medications.1 furthermore, despite our patient’s history of endometrial cancer, her dermatosis developed 6 weeks after cancer resection, mitigating against malignancyassociated ss. blood work also ruled our hematologic malignancy, the most common cause of malignancy-associated ss.2 the most common infectious associations include those of the upper respiratory tract (streptococcus) and gastrointestinal tract (salmonella and yersinia). it is postulated that streptococcal infection induces ss from a hypersensitivity reaction to bacterial antigens.4 the gold standard of therapy for ss is administration of systemic corticosteroids, often beginning with 1 mg/kg/day of prednisone and tapering down to 10 mg/day over 4 to 6 weeks. some patients however, may require treatment for 2 to 3 months.5 in a report by panagiotakis et al, complete remission was achieved after 10 days of antibiotic therapy without the use of systemic corticosteroids.4 similarly, although our patient’s symptoms improved on prednisone, complete resolution of her symptoms occurred after drainage of her pelvic abscess, enabling prednisone to be discontinued. the chronology in this case suggests that group c beta hemolytic streptococcus abscess formation following gynecologic surgery triggered the development of ss. elevated anti-streptolysin o titers can indicate recent or current group a, c and g streptococcal infection. the elevated antistreptolysin o titer was a clue to the underlying infection. cutaneous findings compatible with ss may hint at an underlying infectious complication. conflict of interest disclosures: none. funding: none. corresponding author: matthew a. cornacchia, bs ross university school of medicine miramar, fl matthewacornacchia@gmail.com discussion mailto:matthewacornacchia@gmail.com skin january 2019 volume 3 issue 1 copyright 2018 the national society for cutaneous medicine 38 references: 1. tintle s, patel v, ruskin a, halasz c. azacitidine: a new medication associated with sweet syndrome. j am acad dermatol. 2011. 64(5):e77-9. 2. cohen pr. sweet’s syndrome—a comprehensive review of an acute febrile neutrophilic dermatosis. orphanet j rare dis. 2007;2:34. 3. von den driesch p: sweet's syndrome (acute febrile neutrophilic dermatosis). j am acad dermatol 1994, 31:535-556. 4. lallas a, tzellos tg, papageorgiou m, mandekou-lefaki i. sweet's syndrome associated with upper respir atory tract streptococcal infection: "wait-andsee" strategy or anecdotal use of corticosteroids? hippokratia. 2011;15(3):283. 5. cohen pr, kurzrock r. sweet's syndrome: a review of current treatment options. am j clin dermatol. 2002;3(2):117-31. https://www.ncbi.nlm.nih.gov/pubmed/22435036 skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 380 original research comparison of safety and efficacy of a silicone-based gel containing pracaxi oil (pentaclethra macroloba) versus a silicon-based gel containing cepalin onion extract for the treatment of post-surgical hypertrophic scars mark s. nestor md, phd1,2,3, brian berman md, phd1,2, jessica l. jones do1 1center for clinical and cosmetic research aventura, fl 2department of dermatology and cutaneous surgery, university of miami miller school of medicine, miami, fl 3department of surgery, division of plastic surgery, university of miami miller school of medicine, miami, fl scarring is an unfortunate and unavoidable consequence of cutaneous surgery.1 scar outcomes vary widely from a spectrum of fine and asymptomatic to unappealing keloids. raised hypertrophic scars exist within this scar spectrum and occur by the overexpression of extracellular matrix molecules during the proliferative and remodeling phases of wound healing.2 hypertrophic scars often occur on the shoulders, central chest, upper arms and upper back1 where their increased visibility may be associated with substantial introduction scars are an unavoidable consequence of cutaneous surgery. healing with an excellent cosmetic outcome is a crucial component to any surgical wound to avoid any negative impact on quality of life. various products exist which claim to improve post-surgical scar appearance and texture. in this blinded, randomized pilot study, we compared the efficacy of a siliconebased topical gel containing pracaxi oil (po gel; serica™ moisturizing scar formula; cynova laboratories, houston, tx) against a second silicone-based gel containing cepalin onion extract (oe gel; mederma® advanced scar gel, merz, north america). the vancouver scar scale (vss), physician and subject global assessment of scar treatment, and digital photography were used to determine efficacy and superior post-surgical care treatment outcomes. forty healthy subjects (18-75 years old) with recent surgical scar (1 to 4 months old) were randomized to po gel or oe gel and asked to apply a topical solution three times daily for 8 weeks. there were six study visits (baseline and weeks 2, 4, 8, 12 and 16). the results of this study showed that subjects with post-surgical scars achieved significant improvements at 8 and 12 weeks following application of a product with either pracaxi oil or onion extract gel, based on mean vancouver scar scale scores. both products generally improved the individual scar signs and symptoms. subjects using the onion extract product did not achieve improvement in pain or itch at the 8-week evaluation or pain at the 12-week evaluation. abstract skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 381 psychological distress 3, potentially having a significantly negative impact on quality of life.4,5 silicone gel sheeting and silicone-based gels have been shown to mitigate the development of post-operative scars6-8 and, depending on the anatomical location, silicone gels may offer an advantage over silicone sheeting.9 the use of silicone sheeting or gels is generally considered as a first-line option for extenuating and treating hypertrophic scars.10 current guidelines for treating hypertrophic scars include siliconebased products,3 although the results of a large systematic review concluded clinical trials evaluating silicone gel sheeting as a treatment for hypertrophic scarring are of poor quality and highly susceptible to bias.11 a unique silicone-based gel containing pracaxi oil has been developed for improving the appearance of post-surgical scars (serica™ moisturizing scar formula; cynova laboratories, houston, tx). pracaxi oil is derived from the seed of pentaclethra macroloba, a tree native to south america. it contains the fatty acids oleic acid, linoleic acid, and behenic acid12 which have been shown to enhance wound healing.13,14 an anhydrous silicone-based product containing pracaxi oil was recently shown to have beneficial effects on wound healing15 and scar development.12 the ability of pracaxi oil to improve wound healing may be partly due to its antibiotic activity.16 another alternative silicone-based product, containing the active ingredient cepalin, which is extracted from the allium cepa onion, has also suggested improved postsurgical care outcomes after use (mederma® advanced scar gel, merz, north america). the onion extract contains cepanes which have shown anti-inflammatory properties and anti-infective properties due to the thiosulfinates.25 the objective of this 16-week, randomized, double-blind comparison study was to determine the safety and efficacy of a unique silicone-based gel containing pracaxi oil versus a silicone-based gel containing cepalin onion extract for improving the appearance of hypertrophic surgical scars. inclusion criteria healthy male and female subjects, 18 to 75 years old, were enrolled. subjects were required to have a recent surgical scar, 1 to 4 months old, which was located in an area that could be easily accessed for evaluation and readily allow topical application of the study product by the subjects three times daily. each subject expressed their willingness to complete all study requirements. women of childbearing potential were required to have a negative urine pregnancy test at the baseline study visit and agree to use an accepted method of birth control throughout the study. exclusion criteria reasons for exclusion from study participation included an allergy history or hypersensitivity to any components of the investigational products; uncontrolled diabetes or collagen vascular disorders that affect normal wound healing such as scleroderma, systemic lupus erythematosus or ehler-danlos syndrome; anticipated need for surgery or hospitalization during the study; a target scar which spanned a joint, required the use of a pressure bandage, or was <1 month or >4 months old; pregnancy, methods skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 382 lactation or planned pregnancy during the study; a condition or situation which, in the investigator’s opinion, put the subject at significant risk or would confound the study results; or enrollment in a study involving an investigational drug or device study within the past 30 days. study procedures two test articles were utilized in this study, each with a different active ingredient to compare efficacy outcomes. one test article was a translucent, silicone-based gel containing pracaxi oil (po gel; serica™ moisturizing scar formula; cynova laboratories, houston, tx). the comparator product was a similar-appearing gel containing cepalin, an onion extract (oe gel; mederma® advanced scar gel, merz, north america). each subject received a randomly assigned product in the exact same 30-mg pump bottle labeled with the proper storage conditions and a statement regarding the investigational nature of the product. subjects were randomized in a 1:1 ratio to be treated with the po gel or oe gel. both investigators and subjects were blinded to which product subjects were assigned. each product was to be applied to the target area three times daily, approximately 8 hours apart, for 8 weeks. the study included up to six study visits, which included a baseline (day 0) visit and follow-up visits at weeks 2, 4, 8, 12 and 16. changes in scar appearance were documented with digital photographs obtained at baseline and each follow-up visit. efficacy assessments a modified vancouver scar scale (vss) was used to assess three specific characteristics of scars often observed throughout the remodeling process: vascularity, pliability, and height. the vascularity category was determined upon exam and described as normal, pink, red, or purple then assigned a value of 0, 1, 2, or 3 respectively. additionally, pliability and scar height were quantified with the same scoring system. pliability was assessed as normal (score of 0), supple (score of 1), yielding (score of 2) or firm (score of 3). the height assessment was broken down into flat (score of 0), <2mm (score of 1), 2-5mm (score of 2), or >5mm (score of 3). this study did not assess melanin pigmentation as the vss remains widely applicable to evaluate therapy and as a measure of outcomes.17 using the global assessment of scar treatment, investigators provided an overall assessment of each product’s efficacy for improving scar appearance as very good, good, moderate or unsatisfactory at each visit. subjects were asked to provide scar-associated symptoms of itching and pain and a global assessment of scar treatment which provided an overall satisfaction with the results as very good, good, moderate or unsatisfactory at each visit. safety assessments reports of adverse events (aes) were recorded throughout the trial using medical dictionary for regulatory activities terminology (meddra® msso, version 15.1; mclean, va) and summarized by system organ class, preferred-term, severity, relatedness and seriousness. each subject was counted only once within a system organ class or a preferred term using the event with the greatest relationship and greatest severity. statistical analysis all subjects were included in the summaries of demographic and baseline characteristics. the safety population included subjects skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 383 exposed to any investigational product and who provided any post-application safety information. the efficacy population included subjects who completed the study including the week 16 evaluation. report summaries were generated by biostatistics personnel (agility clinical, carlsbad, ca) using sas® software, version 9.3 (sas institute, inc., cary, nc). quantitative variables were summarized to indicate sample sizes (n), mean, standard deviation (sd), and range (min, max). when applicable, significance testing was performed to assess equivalence between the two treatment groups. confidence intervals were presented to assess equivalence between the two treatment groups. all confidence intervals were two-sided and performed using α=0.05. no formal sample size calculations were performed for this trial. ethics the protocol used in this study and associated materials were approved by a commercial institutional review board (u.s. institutional review board, inc., miami, fl). written informed consent was obtained from each subject including authorization to release health information prior to participating in any study-related activities. enrolled subjects (n=40) were randomized to receive the po gel (n=20) or oe gel (n=20). over the course of the study, three patients did not complete the study. the study was completed through week 16 by 19 subjects in the po gel group (95%) and 18 subjects in the oe gel group (90%). reasons for not completing the study were withdrawal due to aes of pruritus (n=1) and redness (n=1) and loss to follow-up (n=1). demographics and baseline characteristics of the enrolled subjects are summarized in table 1. both groups were well-balanced except for mean scar age, which was significantly older in the oe gel group despite being blindly randomized. efficacy analysis the change in mean composite modified vancouver scar scale scores for po gel and oe gel groups over the course of the study were calculated and are shown in table 2. change in values can also be seen as a graph in graph 1. average vss scores were calculated for each visitbaseline, 8 weeks/end of treatment, and 12 weeks/end of study for both the po and oe gel groups. table 1: demographics and baseline characteristics. pracaxi oil gel n (%) onion extract gel n (%) mean age, years 53.2 54.8 gender male 10 (50) 10 (50) female 10 (50) 10 (50) race caucasian 15 (75) 17 (85) african-american 4 (20) 3 (15) other 1 (5) - ethnicity hispanic/latino 2 (10) 1 (5) non-hispanic/nonlatino 19 (90) 19 (95) mean scar age, days 49.5 70.2a 28-57 15 (75) 9 (45) 58-87 5 (25) 6 (30) 88-118 -5 (25) a significantly different, p=0.008. results skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 384 baseline average scores were then compared to average scores recorded at 8 weeks/end of treatment, and again with average scores observed at 12 weeks/end of study. the po gel scores were significantly different from oe gel scores at each time point although both groups achieved significant improvements in baseline scores. a total -1.8 reduction in score was seen with pracaxi oil at the end of the 12 week study period. additionally, a -2.0 score reduction was demonstrated for the onion extract cohort. it is important to keep in mind, because the vss scale uses very low values, a significant change is needed in any of the individual scores for vascularity, pliability, and scar height in order to produce even a slight change in average vss scores. therefore, it is impressive that both groups experienced nearly a -2.0 score reduction from baseline to end of study. average vss scores for the individual subcategories (vascularity, pliability, and height) were also calculated for both the po gel and oe gel groups (data not shown). table 2: change in mean vancouver scar scale scores. pracaxi oil gel onion extract gel total score day 0 (baseline)a 3.90 3.30 week 8 (end of treatment)b 2.60 1.50 week 12 (end of study)c 2.10 1.33 change in vss score day 0 – week 8 -1.2d -1.8e day 0 – week 12 -1.8f -2.0g between-group comparisons: ap<0.01; bp=0.01; cp<0.05. baseline comparisons: dp=0.005; ep=0.001; fp=0.0001; gp=0.0001. baseline average scores were compared against end of study average scores. pracaxi oil proved to be superior at reducing scar vascularity with a -1.1 overall reduction versus an average of -0.85 score reduction seen with onion extract. however, greater score reductions were calculated for pliability and scar height for those subjects using onion extract. additionally, po gel-treated subjects achieved improvement in the signs and symptoms of each individual vancouver scar scale score, which were greater than oe gel for pain and itch scores at week 8 and pain and vascularity scores at week 12. based on physician and subject global assessment of scar treatment, both groups rated their appearance results as good. safety analysis no significant adverse events were reported during the study. two patients from the oe gel group withdrew due to redness and loss to follow-up, and one patient from the po gel group withdrew secondary to intense itching. pracaxi oil is derived from seeds of the pentaclethra macroloba tree. it contains high concentrations of fatty acids18 with known emollient and medicinal effects including antibacterial activity,16,19,20 enhancing wound healing,13,14 antiproteolytic and antihemorrhagic properties21,22 and are essential to the formation and maintenance of cell membranes within the stratum corneum. cepalin onion extracts have also demonstrated similar wound healing benefits due to anti-inflammatory properties and antimicrobial properties. these benefits are attributed to the biochemical thiosulfinates.25 discussion skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 385 figure 1: change in mean vancouver scar scale scores over study length. cepalin is extracted from the allium cepa onion. data from in vitro studies suggested that the onion extract exhibits antiinflammatory, antiproliferative, bacteriostatic, and collagen down regulatory properties by its effect on fibroblast and mast cell. the therapeutic effects of topical anhydrous silicone base containing pracaxi oil was initially demonstrated in a case series of patients with surgical, traumatic, or burn wounds and scars.12 the product was applied two to four times daily based on the size and severity of the scar or wound. the mean duration of application of the pracaxi oil product was 11 days and ranged from 48 hours to 3 weeks. among the 21 enrolled patients, self-reported questionnaire results and clinical photographs were obtained for seven. using an 11-point (0-10) satisfaction scale, the mean (sd) score was 10 (1.15). one patient with a 1-year old hypertrophic surgical scar reported the thickness, color, and overall scar severity were improved after 1 week of treatment. the overall objective of this study was to compare the efficacy and safety of a siliconebased gel containing pracaxi oil against a gel containing onion extract for treating hypertrophic scars. the ability of onion extract to improve the appearance of surgical scars has previously been assessed in several clinical studies. however, in those studies oe gel was compared against silicone sheeting, and ultimately demonstrated mixed results. two randomized studies showed silicone gel containing onion extract was more effective than the silicone gel vehicle for treating postsurgical hypertrophic scars.23,24 one study showed that onion extract gel significantly improved post-surgical scar softness, redness, texture, and global appearance.25 in another study, onion extract reduced the height of hypertrophic scars but did not improve redness and overall appearance.26 two studies found onion extract had no effect on post-surgical scars27,28 while one reported it was less effective than silicone gel sheeting.29 the vss was a critical component of this study in measuring the efficacy of treatment outcomes by assessing vascularity, height/thickness and pliability of each scar. reduction in vss scores were calculated from each group for weeks 0-8 and again weeks 8-12. a -1.8 reduction in score was seen with pracaxi oil at the end of the 12 week study period. additionally, a -2.0 score reduction was demonstrated for the onion extract cohort. the results of the present study showed that subjects with post-surgical scars achieved significant improvements at 8 and 12 weeks following application of a product with either pracaxi oil or onion extract gel, based on mean vancouver scar scale scores, and both products generally improved the individual scar signs and symptoms. subjects using the onion extract product did not 0.00 0.50 1.00 1.50 2.00 2.50 3.00 3.50 4.00 4.50 baseline week 8 week 12 vs s sc or e visit by week pracaxi oil onion extract skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 386 achieve improvement in pain or itch at the 8week evaluation or pain at the 12-week evaluation; however, the baseline scores for these symptoms were already very low. neither product achieved any improvement in the physician or subject global assessment of scar treatment scores. one of the main limitations to this study is the fact that this is a pilot study, as the sample size is small with 40 total subjects. a limitation to the study was the significant difference in mean scar age at baseline. despite randomization, scars were significantly older for subjects in the onion extract group. this might account for the higher baseline composite vancouver scar scale scores scale for the pracaxi oil gel group (3.9 vs. 3.3) and possibly lower pain and itch scores. as this imbalance was probably due to small sample sizes, a larger randomized study is likely to be more balanced. the results of this study indicate a topical silicone-based pracaxi oil gel is as effective as an onion extract gel for improving the appearance of hypertrophic post-surgical scars. larger controlled studies will be necessary to further evaluate the overall potential of this product for improving the unsightly appearance of hypertrophic scars. conflict of interest disclosures: dr. nestor is an investigator for cynova laboratories. funding: study sponsored by cynova laboratories. corresponding author: mark s. nestor, md, phd center for clinical and cosmetic research 2925 aventura boulevard, suite 205 aventura, fl email: nestormd@admcorp.com references: 1) clayton as, stasko t. surgical complications and optimizing outcomes. in: bolognia jl, jorizzo jl, schaffer jv, eds. dermatology. vol 3. atlanta: elsevier inc; 2016. 2) sidgwick gp, mcgeorge d, bayat a. a comprehensive evidence-based review on the role of topicals and dressings in the management of skin scarring. arch dermatol res. 2015;307:461-477. 3) meaume s, le pillouer-prost a, richert b, roseeuw d, vadoud j. management of scars: updated practical guidelines and use of silicones. eur j dermatol. 2014;24:435-443. 4) bock o, schmid-ott g, malewski p, mrowietz u. quality of life of patients with keloid and hypertrophic scarring. arch dermatol res. 2006;297:433-438. 5) choi y, lee jh, kim yh, lee ys, chang hs, park cs, roh mr. impact of postthyroidectomy scar on the quality of life of thyroid cancer patients. ann dermatol. 2014;26:693-699. 6) kim js, hong jp, choi jw, seo dk, lee es, lee hs. the efficacy of a silicone sheet in postoperative scar management. adv skin wound care. 2016;29:414-420. 7) medhi b, sewal rk, kaman l, kadhe g, mane a. efficacy and safety of an advanced formula silicone gel for prevention of postoperative scars. dermatol ther (heidelb). 2013;3:157-167. 8) spencer jm. case series: evaluation of a liquid silicone gel on scar appearance following excisional surgery--a pilot study. j drugs dermatol. 2010;9:856-858. limitations conclusion mailto:nestormd@admcorp.com skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 387 9) kim sm, choi js, lee jh, kim yj, jun yj. prevention of postsurgical scars: comparsion of efficacy and convenience between silicone gel sheet and topical silicone gel. j korean med sci. 2014;29(suppl 3):s249-253. 10) monstrey s, middelkoop e, vranckx jj, bassetto f, ziegler ue, meaume s, téot l. updated scar management practical guidelines: non-invasive and invasive measures. j plast reconstr aesthet surg. 2014;67:1017-1025. 11) o'brien l, pandit a. silicon gel sheeting for preventing and treating hypertrophic and keloid scars. cochrane database syst rev. 2006;1:cd003826. 12) banov d, banov f, bassani as. case series: the effectiveness of fatty acids from pracaxi oil in a topical silicone base for scar and wound therapy. dermatol ther (heidelb). 2014;4:259269. 13) ruthig dj, meckling-gill ka. both (n-3) and (n-6) fatty acids stimulate wound healing in the rat intestinal epithelial cell line, iec-6. j nutr. 1999;129:17911798. 14) cardoso cr, souza ma, ferro ea, favoreto s jr, pena jd. influence of topical administration of n-3 and n-6 essential and n-9 nonessential fatty acids on the healing of cutaneous wounds. wound repair regen. 2004;12:235-243. 15) simmons cv, banov f, banov d. use of a topical anhydrous silicone base containing fatty acids from pracaxi oil in a patient with a diabetic ulcer. sage open med case rep. 2015;3:2050313x15589676. 16) guimarães al, cunha ea, matias fo, garcia pg, danopoulos p, swikidisa r, pinheiro va, nogueira rj. antimicrobial activity of copaiba (copaifera officinalis) and pracaxi (pentaclethra macroloba) oils against staphylococcus aureus: importance in compounding for wound care. int j pharm compd. 2016;20:58-62. 17) nedelec b, shankowsky ha, tredget ee. rating the resolving hypertrophic scar: comparison of the vancouver scar scale and scar volume. j burn care rehabil. 2000;21:205-212. 18) dos santos costa mnf, muniz map, negrao cab, et al. characterization of pentaclethra macroloba oil. j therm anal calorim. 2014;115:2269-2275. 19) oliveira aa, segovia jf, sousa vy, mata ec, gonçalves mc, bezerra rm, junior po, kanzaki li. antimicrobial activity of amazonian medicinal plants. springerplus. 2013;2 371. 20) leal icr, junior ii, pereira em, laport ms, kuster km, dos santos krn. pentaclethra macroloba tannins fractions active against methicillinresistant staphylococcal and gram negative strains showing selective toxicity. rev bras farmacogn. 2011;21:991–999. 21) da silva jo, coppede js, fernandes vc, santana cd, ticli fk, mazzi mv, giglio jr, pereira ps, soares am, sampaio sv. antihemorrhagic, antinucleolytic and other antiophidian properties of the aqueous extract from pentaclethra macroloba. j ethnopharmacol. 2005;100:145-152. 22) da silva jo, fernandes rs, ticli fk, oliveira cz, mazzi mv, franco jj, giuliatti s, pereira ps, soares am, sampaio sv. triterpenoid saponins, new metalloprotease snake venom inhibitors isolated from pentaclethra macroloba. toxicon. 2007;50:283-291. 23) jenwitheesuk k, surakunprapha p, jenwitheesuk k, kuptarnond c, skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 388 prathanee s, intanoo w. role of silicone derivative plus onion extract gel in presternal hypertrophic scar protection: a prospective randomized, double blinded, controlled trial. int wound j. 2012;9:397-402. 24) wananukul s, chatpreodprai s, peongsujarit d, lertsapcharoen p. a prospective placebo-controlled study on the efficacy of onion extract in silicone derivative gel for the prevention of hypertrophic scar and keloid in median sternotomy wound in pediatric patients. j med assoc thai. 2013;96:1428-1433. 25) draelos zd. the ability of onion extract gel to improve the cosmetic appearance of postsurgical scars. j cosmet dermatol. 2008;7:101-104. 26) chanprapaph k, tanrattanakorn s, wattanakrai p, wongkitisophon p, vachiramon v. effectiveness of onion extract gel on surgical scars in asians. dermatol res pract. 2012;2012:212945. 27) jackson ba, shelton aj. pilot study evaluating topical onion extract as treatment for postsurgical scars. dermatol surg. 1999;25:267-269. 28) chung vq, kelley l, marra d, jiang sb. onion extract gel versus petrolatum emollient on new surgical scars: prospective double-blinded study. dermatol surg. 2006;32:193-197. 29) karagoz h, yuksel f, ulkur e, evinc r. comparison of efficacy of silicone gel, silicone gel sheeting, and topical onion extract including heparin and allantoin for the treatment of postburn hypertrophic scars. burns. 2009;35:1097-1103. open-label extension study evaluating the long-term safety, efficacy, and tolerability of fmx103 1.5% topical minocycline foam in the treatment of moderate-to-severe facial papulopustular rosacea linda stein gold, md1, james q. del rosso, do2, leon kircik, md3, neal d. bhatia, md4, deirdre hooper, md5, walter nahm, md, phd6, iain stuart, phd7 1henry ford health system, detroit, mi; 2jdr dermatology research/thomas dermatology, las vegas, nv; 3icahn school of medicine at mount sanai, new york, ny; 4therapeutics clinical research, san diego, ca; 5delricht research, new orleans, la; 6university of california, san diego school of medicine, san diego, ca; 7vyne therapeutics inc., bridgewater, nj introduction • rosacea is a chronic, inflammatory disorder involving the face that is characterized by central facial erythema, flushing, telangiectasia, edema, papules, and pustules1-3 • oral tetracyclines, such as doxycycline and minocycline, are among the common therapies that are used for treating the disorder with oral, sub-microbial doxycycline currently approved for this indication. however, these agents have been associated with antibiotic resistance, adverse side effects, such as gastrointestinal upset and permanent hyperpigmentation, and following treatment cessation, the tendency for disease relapse is high3-7 • the efficacy and safety of fmx103 1.5% topical minocycline foam in treating moderate-to-severe rosacea have previously been reported in two, 12-week, double-blind, vehicle-controlled, phase 3 studies (study 11 and study 12)8 • objective: to demonstrate the long-term safety, tolerability and efficacy of topical fmx103 1.5% minocycline foam in moderate to severe facial papulopustular rosacea for up to 52 weeks. methods • fx2016-13 (study 13) was an open-label, multicenter, 40-week extension study to evaluate the long-term safety, tolerability, and efficacy of fmx103 1.5% topical foam in the treatment of moderate-to-severe facial papulopustular rosacea (figure 1) • subjects were eligible to enter study 13 upon successful completion of either double-blind study (study 11 or study 12) – there was no limit on the number of subjects who could enter the open-label phase • concomitant use of prescription or otc medications that the subjects were taking or any change in dosage was permitted and recorded • investigator global assessments (igas) were based upon a 5-point scale with 0=clear, 1=almost clear, 2=mild, 3=moderate, and 4=severe figure 1. study design week 52baseline key inclusion criteria for db study • males and nonpregnant females ≥18 years • moderate-to-severe facial papulopustular rosacea (iga score of 3 or 4) • >15 to ≤75 facial papules and pustules, excluding lesions involving eyes and scalp; ≤2 nodules on the face • presence or history of facial erythema or flushing co-primary efficacy endpoints • absolute change in the inflammatory lesion count at week 52 compared to db baseline • iga success rate (dichotomized as yes/no) at week 52, where success was defined as an iga score of 0 or 1, and at least a 2-grade improvement (decrease) from db baseline secondary efficacy endpoints • the absolute and percent change from db baseline in inflammatory lesion count at weeks 16, 22, 28, 34, 40, 46, and 52 of the ol study • the dichotomized iga success rate at weeks 16, 22, 28, 34, 40, and 46 • the subject satisfaction questionnaire (ssq) at week 52 week 12 fmx103 1.5% (505 enrolled, 504 in safety population, 410 completed) double-blind, vehicle-controlled (n=1522) open-label (fx2016-13) for subjects who completed the db study visit every 6 weeks vehicle foam (n=256) fmx103 1.5% (n=495) vehicle foam (n=257) fmx103 1.5% (n=514) s tu dy 1 1 s tu dy 1 2 iga, investigator’s global assessment; db, double-blind study; ol, open-label study; otc, over-the-counter. results subject disposition and double-blind baseline demographics • as shown in figure 2, 504 subjects who completed the db study (study 11: n=217; study 12: n=287) comprised the all treated (safety) population in the ol extension study (study 13) figure 2. subject disposition 3 discontinuation adverse event = 5 abnormal laboratory follow-up = 0 lost to follow-up = 29 subject request = 50 protocol deviation = 0 other = 9completed ol study (n=410) fmx103/fmx103, n=276 (83%) vehicle/fmx103, n=134 (78%) study 11 randomized (n=751) completed db study (fmx103 1.5%) n=437 completed db study (vehicle) n=232 entered ol study n=140 (32%) entered ol study n=77 (24%) study 12 randomized (n=771) completed db study (fmx103 1.5%) n=479 completed db study (vehicle) n=239 entered ol study n=192 (40%) entered ol study n=95 (40%) study 13 total entering ol study (n=505*) total in safety population (n=504) fmx103/fmx103, n=332 (36%) vehicle/fmx103, n=172 (37%) *one subject who was enrolled discontinued the same day prior to taking the study drug and was therefore excluded from the safety population. • double-blind demographics, double-blind baseline characteristics, and concomitant use of medication during the ole study are shown in table 1 table 1. double-blind baseline demographics, disease characteristics, and concomitant use of medication variable fmx103/ fmx103 (n=332) vehicle foam/ fmx103 (n=172) overall (n=504) mean age (sd) 18 to 40 years 41 to 64 years ≥ 65 years 51.1 (12.62) 68 (20.5) 214 (64.5) 50 (15.1) 51.9 (11.90) 26 (15.1) 121 (70.3) 25 (14.5) 51.4 (12.37) 94 (18.7) 335 (66.5) 75 (14.9) gender, n (%) male female 91 (27.4) 241 (72.6) 62 (36.0) 110 (64.0) 153 (30.4) 351 (69.6) race, n (%) white black other 321 (96.7) 5 (1.5) 6 (1.8) 163 (95.3) 3 (1.8) 6 (1.8) 484 (96.2) 8 (1.6) 12 (2.4) mean inflammatory lesion count, n (sd) 28.8 (12.63) 28.7 (11.93) 28.8 (12.38) iga score, n (%) 3 – moderate 4 – severe 301 (90.7) 31 (9.3) 149 (86.6) 23 (13.4) 450 (89.3) 54 (10.7) any concomitant medication during the study, n (%) vitamins lipid modifying agents agents acting on the renin-angiotensin system antibiotics and chemotherapeutics for dermatological use antifungals for dermatological use other dermatological preparations 273 (82.2) 81 (24.4) 76 (22.9) 72 (21.7) 6 (1.8) 6 (1.8) 9 (2.7) 137 (79.7) 39 (22.7) 38 (22.1) 35 (20.3) 4 (2.3) 1 (0.6) 3 (1.7) 410 (81.3) 120 (23.8) 114 (22.6) 107 (21.2) 10 (2.0) 7 (1.4) 12 (2.4) baseline is defined as the baseline visit in the double-blind study; iga, investigator’s global assessment; sd, standard deviation. safety and tolerability • summary of all adverse events in the all treated population is shown in table 2 • the majority of the treatment-emergent adverse events (teaes) were considered mild or moderate in severity and no serious teaes were related to treatment table 2. summary of teaes, rates of discontinuation and overall fmx103 1.5% treatment duration in the ol extension variable fmx103 1.5%/ fmx103 1.5% (n=332) vehicle foam/ fmx103 1.5% (n=172) overall (n=504) subjects with any ae, n (%) 151 (45.5) 70 (40.7) 221 (43.8) subjects with any teae, n (%) 137 (41.3) 64 (37.2) 201 (39.9) subjects with any serious teae, n (%) 9 (2.7)a 4 (2.3)b 13 (2.6) subjects with treatment-related teaes, n (%) 5 (1.5)c 8 (4.7)d 13 (2.6) subjects with serious treatment-related teaes, n (%) 0 (0.0) 0 (0.0) 0 (0.0) subjects discontinued due to ae, n (%) 3 (0.9)e 2 (1.2)f 5 (1.0) teaes resulting in death, n (%) 0 (0.0) 0 (0.0) 0 (0.0) subjects exposed to > 6 months (>168 days), n (%) 319 (96.1) 146 (84.9) 465 (92.3) subjects exposed to > 1 year (>350 days), n (%) 272 (81.9) 0 (0.0) 272 (54.0) number (%) of subjects with at least 1 ae per category; ae, adverse event; teae, treatment-emergent adverse event alabyrinthitis, periorbital cellulitis, pneumonia, staphylococcal infection, cerebrospinal fluid leakage, cerebrovascular accident, syncope, subdural hematoma, death, hypokalemia, malignant melanoma bappendicitis perforated, post procedural hemorrhage, large intestinal instruction, chronic obstructive pulmonary disease cmydriasis, angular cheilitis, herpes simplex, dermatitis contact, hair color changes ddiarrhea, conjunctivitis, sunburn, acne, dermatitis contact, erythema, pruritus, rosacea, skin lesion edermatitis contact, mydriasis, enchondromatosis frosacea, anemia, leukocytosis, appendicitis perforated, sepsis, appendicectomy • teaes occurring in at least 2% of open-label subjects from either arm of the double-blind phase are shown in table 3 table 3. teaes in the ol extension variable fmx103 1.5%/ fmx103 1.5% (n=332) vehicle foam/ fmx103 1.5% (n=172) overall (n=504) subjects with one or more teae, n (%) 137 (41.3) 64 (37.2) 201 (39.9) infections and infestations upper respiratory tract infection viral upper respiratory tract infection sinusitis influenza bronchitis urinary tract infection 14 (4.2) 14 (4.2) 8 (2.4) 9 (2.7) 8 (2.4) 8 (2.4) 5 (2.9) 5 (2.9) 9 (5.2) 5 (2.9) 2 (1.2) 1 (0.6) 19 (3.8) 19 (3.8) 17 (3.4) 14 (2.8) 10 (2.0) 9 (1.8) nervous system disorders headache 8 (2.4) 2 (1.2) 10 (2.0) vascular disorders hypertension 7 (2.1) 1 (0.6) 8 (1.6) teae, treatment-emergent adverse event • local facial assessments at week 52 demonstrated that fmx103 1.5% topical minocycline foam was well tolerated during the ol extension study (figure 3) figure 3. facial tolerability assessed at week 52 0 14.2 3.8 0.2 45.1 29.0 29.4 66.3 10.7 0% 25% 50% 75% 100% bl wk 52 erythema 1.5 0.5 1.0 0.70.5 0.4 chart title0=none 1=mild 2=moderate 3=severe 6.0 19.0 64.7 97.0 17.1 57.6 45.2 80.3 53.6 86.3 62.1 90.0 62.1 79.1 57.5 66.3 23.4 3.0 42.3 36.9 38.3 18.2 35.3 13.2 30.6 9.0 30.6 20.2 36.5 14.7 11.9 36.9 5.0 16.5 10.7 7.3 7.3 3.8 0% 25% 50% 75% 100% bl wk 52 bl wk 52 bl wk 52 bl wk 52 bl wk 52 bl wk 52 bl wk 52 % o f p op ul at io n hyperpigmentation peeling/ desquamation itchingdryness/ xerosis flushing/ blushing burning/ stinging telangiectasia clear severe moderate mild almost clear 0.8 0.5 note: percentages exclude missing responses as 60 responses were missing from the fmx103/fmx103 group (n=272) and 43 responses were missing from the vehicle/fmx103 group (n=129). bl refers to baseline of the double-blind study hyperpigmentation was evaluated as post-inflammatory hyperpigmentation long-term efficacy • treatment with fmx103 1.5% during the 40-week ol extension study was associated with reduction in inflammatory lesions relative to the db and ol baselines, regardless of previous treatment during the db studies (figure 4) figure 4. absolute (a) and percent (b) change from db baseline in inflammatory lesions -100 -75 -50 -25 0 0 4 8 12 16 22 28 34 40 46 52 % r ed uc tio n fr om d b b as el in e in in fla m m at or y le si on c ou nt -25 -20 -15 -10 -5 0 0 4 8 12 16 22 28 34 40 46 52 m ea n re du ct io n fr om d b b as el in e in in fla m m at or y le si on c ou nt db study vehicle group switched to active treatment fmx103 1.5%/fmx103 1.5% (n=332) ba -46.4% 62.4% 80.9% 83.0% vehicle/fmx103 1.5% (n=172) db study vehicle group switched to active treatment fmx103 1.5%/fmx103 1.5% (n=332) -12.8 17.9 vehicle/fmx103 1.5% (n=172) -22.5 -23.0 week week db, double-blind study; change from baseline is calculated as the value at baseline minus the post-baseline value • at the end of the study, 81.6% of the fmx103/fmx103 patients, and 76.0% of the vehicle/fmx103 patients, achieved iga treatment success (figure 5) figure 5. iga treatment success 0 19 37.8 47.6 50.6 60.1 68.1 69.1 72.4 73.5 81.6 0.0 12.2 32.6 39.0 48.2 54.5 64.0 64.4 65.9 72.1 76.0 0 25 50 75 100 0 4 8 12 16 22 28 34 40 46 52 % o f p op ul at io n w ith ig a t re at m en t s uc ce ss week fmx103/fmx103 vehicle/fmx103 number of subjects remaining in the study week 0 4 8 12 16 22 28 34 40 46 52 fmx103/ fmx103 332 332 331 332 326 321 310 298 286 279 272 vehicle/ fmx103 172 172 172 172 168 156 150 146 138 136 129 db study * db, double-blind study; iga, investigator’s global assessment *week 12 of the db study serves as the baseline for the ole study subject satisfaction • at the end of the open-label study there was a high rate of subject satisfaction with fmx103 1.5% for the treatment of papulopustular rosacea (figure 6) figure 6. subject satisfaction questionnaire results at week 52 all treated population, n=504 compared to other products 55%28% 11% 5% 1% 59%24% 11% 5% 1% overall satisfaction with product 59%24% 9% 7% 1% recommend to friend very satisfied very dissatisfieddissatisfied somewhat satisfiedsatisfied very likely very unlikelyunlikely somewhat likelylikely percentages exclude 110 missing responses summary limitations • because of the nature of the open-label study, no inference can be made on comparability due to the absence of a vehicle-treated control conclusions • fmx103 1.5% appeared to be safe and well tolerated for the long-term treatment of papulopustular rosacea for up to 52 weeks of treatment • no minocycline-induced hyperpigmentation was observed • throughout 52 weeks of treatment, fmx103 1.5% continued to be associated with a decreasing number of inflammatory lesions, as well as with improvement in overall disease severity, as assessed by iga scores • patient satisfaction levels were high, with >80% of all subjects being either satisfied or very satisfied with fmx103 1.5% disclosures/acknowledgment disclosures dr. stein gold is an advisor and investigator for foamix, galderma, leo pharma, novartis, and valeant and is an investigator for janssen, abbvie, and solgel and an advisor and investigator for novartis. dr. del rosso is a consultant for aclaris, almirall, athenex, cutanea, dermira, ferndale, galderma, genentech, leo pharma, menlo, novan, ortho, pfizer, promius, sanofi/regeneron, skinfix, and sunpharma; he has received research support from aclaris, almirall, athenex, botanix, celgene, cutanea, dermira, galderma, genentech, leo pharma, menlo, novan, ortho, promius, regeneron, sunpharma, and thync; he receives honoraria from aclaris, celgene, galderma, genentech, leo pharma, novartis, ortho, pfizer, promius, sanofi/regeneron, and sunpharma; and he participates in speakers bureaus for honoraria from aclaris, celgene, galderma, genentech, leo pharma, novartis, ortho, pfizer, promius, sanofi/regeneron, and sunpharma. dr. bhatia is an investigator and consultant for foamix pharmaceuticals. dr. hooper served as an investigator for foamix pharmaceuticals; she reports personal fees from delricht research during the conduct of the study; honoraria from allergan, almirall aesthetics, aqua galderma usa, cutera, inc., ferndale, la roche posay, pixacore, rbc consultants (clarisonic), revance, and viviscal; and other financial benefits from actavis, dermira, gsk, mylan, and sol gel. dr. nahm is an investigator for foamix pharmaceuticals. dr. iain stuart is an employee and stockholder at vyne therapeutics inc. this study is funded by foamix pharmaceuticals ltd, a wholly owned subsidiary of vyne therapeutics inc. acknowledgment editorial support was provided by scient healthcare communications. references 1. li wq, cho e, khalili h, et al. rosacea, use of tetracycline, and risk of incident inflammatory bowel disease in women. clin gastroenterol hepatol. 2016;14(2):220-225. 2. taieb a, stein gold l, feldman sr, et al. cost-effectiveness of ivermectin 1% cream in adults with papulopustular rosacea in the united states. j manag care spec pharm. 2016;22(6):654-665. 3. rainer bm, kang s, chien al. rosacea: epidemiology, pathogenesis, and treatment. dermatoendocrinol. 2017;9(1):e131574. 4. goldgar c, keahey dj, houchins j. treatment options for acne rosacea. am fam physician. 2009;80(5):461-468. 5. oge lk, munchie hl, phillips-savoy ar. rosacea: diagnosis and treatment. am fam physician. 2015;92(3):187-196. 6. fiscus v, hankinson a, alweis r. minocycline-induced hyperpigmentation. j community hosp. 2014;4:24063. 7. valentín s, morales a, sánchez jl, rivera a. safety and efficacy of doxycycline in the treatment of rosacea. clin cosmet investig dermatol. 2009;2:129-140. 8. stein gold l, del rosso jq, kircik l, et al. minocycline 1.5% foam for the topical treatment of moderate-to-severe papulopustular rosacea: results of two phase 3, randomized, clinical trials. j am acad dermatol. in press. acknowledgements: medical writing support was provided by prescott medical communications group (chicago, il) with financial support from ortho dermatologics; ortho dermatologics is a division of bausch health us, llc • presented at fall clinical 2020 • october 29 november 1, 2020 • virtual synopsis � in the treatment of psoriasis, combining tazarotene (taz) with a potent topical steroid, such as the superpotent corticosteroid halobetasol propionate (hp), is recommended for patients with mild-to-moderate disease1 � the taz + hp combination may provide synergistic efficacy, increase the duration of treatment effect and time of remission, and reduce side effects of both hp and taz1-3 � topical psoriasis therapy has also been recommended for patients with lower levels of body surface area (bsa) involvement4; though these patients may be deemed more “mild,” they may nonetheless have disease characteristics that severely impact their quality of life (qol) � a once-daily, fixed combination hp 0.01%/taz 0.045% lotion (duobrii,® ortho dermatologics) was developed to address these unmet needs in the topical treatment of psoriasis objective � to evaluate the efficacy, impact on qol, and safety of hp 0.01%/taz 0.045% lotion versus vehicle in patients with lower levels of bsa involvement (3–5%) at baseline methods figure 1. phase 3, randomized, double-blind, vehicle controlled studies of halobetasol propionate 0.01%/tazarotene 0.045% lotion5,6 randomized, double-blind, vehicle-controlled treatment study 1 (nct02462070) posttreatment follow-up (no treatment) baseline 2:1 week 12 hp/taz lotion (n=135) vehicle lotion (n=68) week 8 study 2 (nct02462122) 2:1 hp/taz lotion (n=141) vehicle lotion (n=74) baseline 2:1 week 12 key eligibility criteria: • ≥18 years old • iga of 3 (moderate) or 4 (severe) • affected bsa 3% to 12% assessments: • treatment successa • affected bsa • dlqi • adverse events and local skin reactions week 8 2:1 pooled, post hoc analysis: • conducted in 232 participants with 3–5% bsa (hp/taz lotion, n=149; vehicle lotion, n=83) adefined as percentage of participants achieving ≥2-grade reduction from baseline in iga and a score of ‘clear’ (0) or ‘almost clear’ (1). in these studies, cerave® hydrating cleanser and cerave® moisturizing lotion (l’oreal, ny) were provided as needed for optimal moisturization/ cleaning of the skin. bsa, body surface area; dlqi, dermatology life quality index; hp/taz, halobetasol propionate 0.01% and tazarotene 0.045%; iga, investigator’s global assessment; itt, intent to treat. results demographics and baseline characteristics � a total of 418 participants were included in the overall study population (baseline bsa of 3–12%; mean: 5.9%); of these participants, 232 (55.5%) had baseline bsa of 3–5% (mean: 3.8%) � participant demographics (age, sex, race) were similar between groups, though a higher proportion of participants with 3–5% bsa had a baseline investigator’s global assessment (iga) score of 3 (moderate; 91.8%) versus the overall population (85.2%) figure 4. clinically meaningful improvement in quality of lifea in 3–5% bsa subgroup and overall populationb (itt population, pooled) 20% 40% 60% 80% p e rc e n ta g e o f p a rt ic ip a n ts a ch ie vi n g ≥ 4 -g ra d e r e d u ct io n i n d lq i 0% 4 8 12 study visit (weeks) treatment posttreatment hp/taz lotion: bsa 3-5% (n=149) hp/taz lotion: overall (n=200) vehicle lotion: bsa 3-5% (n=83) vehicle lotion: overall (n=107) 0 ** **** hp/taz lotion: • significantly superior to vehicle at week 8 in improving quality of life maintenance of effect: • statistical superiority maintained 4 weeks posttreatment *p<0.05 vs vehicle; **p<0.01 vs vehicle. adefined as ≥4-point reduction (improvement) in dlqi score7. boverall population had baseline bsa ranging from 3 to 12%. total dlqi score ranges from 0–30, with higher scores indicating worse quality of life. n values shown for baseline. bsa, body surface area; dlqi, dermatology life quality index; hp/taz, halobetasol propionate 0.01% and tazarotene 0.045%; itt, intent to treat. figure 5. improvement of psoriasis with once-daily hp/taz lotion baseline week 4 week 8 week 12 target lesion this figure shows representative images from a single participant (target lesion on upper back). participant bsa: baseline, 3%; weeks 4, 8, and 12, 1%. participant iga: baseline, 3 (moderate); weeks 4, 8, and 12, 1 (almost clear). participant dlqi: baseline, 5; week 4, 0; week 8, 1; week 12, 0. bsa, body surface area; dlqi, dermatology life quality index; hp/taz, halobetasol propionate 0.01% and tazarotene 0.045%; iga, investigator’s global assessment. adverse events � incidence of treatment-emergent adverse events (teaes) with hp/taz was similar between the bsa 3–5% subgroup and the overall population; the most common teaes were also similar between groups (table 1) � in a separate analysis by baseline iga, hp/taz-treated participants with moderate psoriasis (iga 3) experienced fewer irritation-related aes than those with severe psoriasis (iga 4; data not shown) halobetasol 0.01%/tazarotene 0.045% (hp/taz) lotion for the treatment of plaque psoriasis in patients with 3-5% body surface area efficacy and quality of life figure 2. treatment successa in 3–5% bsa subgroup and overall populationb (itt population, pooled) p e rc e n ta g e o f p a rt ic ip a n ts 0% 10% 20% 30% 40% 50% 60% 0 2 4 6 8 12 study visit (weeks) treatment posttreatment ****** hp/taz lotion: bsa 3-5% (n=149) hp/taz lotion: overall (n=276) vehicle lotion: bsa 3-5% (n=83) vehicle lotion: overall (n=142) hp/taz lotion: • significantly superior to vehicle at all study visits • over 40% of participants achieved treatment success at week 8 maintenance of effect: • statistical superiority maintained 4 weeks posttreatment • of the participants that achieved treatment success at week 8, most maintained success at week 12 • 3–5% bsa: 63.3% maintained • overall: 62.4% maintained *** *** *** ****** ****** *p<0.05 vs vehicle; **p<0.01 vs vehicle; ***p<0.001 vs vehicle. adefined as percentage of participants achieving ≥2-grade reduction from baseline iga and a score of ‘clear’ (0) or ‘almost clear’ (1). boverall population had baseline bsa ranging from 3 to 12%. bsa, body surface area; hp/taz, halobetasol propionate 0.01% and tazarotene 0.045%; iga, investigator’s global assessment; itt, intent to treat. figure 3. bsa reduction in 3–5% bsa subgroup and overall populationa (itt population, pooled) 0% -50% -40% -30% -20% -10% 10% m e a n p e rc e n t c h a n g e f ro m b a se lin e -60% 2 4 6 8 12 study visit (weeks) treatment posttreatment hp/taz lotion: bsa 3-5% (n=149) hp/taz lotion: overall (n=276) vehicle lotion: bsa 3-5% (n=83) vehicle lotion: overall (n=142) 0 **** ****** ****** ****** ****** hp/taz lotion: • significantly superior to vehicle at all study visits • over 35% reduction in bsa from baseline to week 8 maintenance of effect: • statistical superiority maintained 4 weeks posttreatment **p<0.01 vs vehicle; ***p<0.001 vs vehicle. aoverall population had baseline bsa ranging from 3 to 12%. bsa, body surface area; hp/taz, halobetasol propionate 0.01% and tazarotene 0.045%; itt, intent to treat. table 1. treatment-emergent adverse events bsa 3–5% subgroup overall population hp/taz lotion (n=148) vehicle lotion (n=82) hp/taz lotion (n=270) vehicle lotion (n=140) any teae, n (%) 55 (37.2) 16 (19.5) 97 (35.9) 30 (21.4) most common teaesa, n (%) contact dermatitis 11 (7.4) 0 20 (7.4) 0 pruritis 4 (2.7) 2 (2.4) 8 (3.0) 4 (2.9) folliculitis 4 (2.7) 0 5 (1.9) 0 burning sensationb 4 (2.7) 1 (1.2) 4 (1.5) 3 (2.1) application site pain 3 (2.0) 0 7 (2.6) 1 (0.7) nasopharyngitisc 2 (1.4) 2 (2.4) 5 (1.9) 4 (2.9) aat least 2.5% incidence in any treatment group. bsystem organ class: nervous system disorder. cno instances were considered by the investigator to be treatment related. bsa, body surface area; hp/taz, halobetasol propionate 0.01% and tazarotene 0.045%; teae, treatment-emergent adverse event. � skin atrophy was reported as an ae in 5 (1.9%) participants who received hp/taz lotion; of those, 2 (1.4%) had baseline bsa 3–5% • no participants who received vehicle reported skin atrophy as an ae local skin reactions � itching, dryness, and burning/stinging showed improvements over 8 weeks of hp/taz treatment in the bsa 3–5% subgroup and the overall population (data not shown) � in hp/taz-treated participants; the bsa 3–5% subgroup and overall population had low peak incidence of skin atrophy (4.4% and 2.9%, respectively), striae (0.7% and 1.3%), telangiectasias (0.7% and 0.8%), and folliculitis (2.2% and 2.9%) • incidence peaked at week 8 for all assessments except telangiectasias, which peaked at week 6 in the overall population • among participants treated with vehicle lotion, incidence of these local skin reactions was 0.5%-1.5% at all study visits conclusions � in two pooled phase 3 studies, hp/taz lotion demonstrated rapid efficacy versus vehicle and clinically meaningful improvement in qol among participants with lower (3–5%) affected bsa at baseline, with improvements maintained 4 weeks posttreatment � hp/taz lotion was well tolerated, with low rates of skin atrophy and other local skin reactions � hp/taz lotion may be an effective and well tolerated option for the treatment of “milder” psoriasis in patients with lower bsa involvement references 1. elmets ca, et al. j am acad dermatol. online ahead of print, 2020 jul 30. doi:10.1016/j.jaad.2020.07.087. 2. tanghetti e, et al. j dermatolog treat. 2019:1-8. 3. kircik lh, et al. j drugs dermatol. 2019;18(3):279-284. 4. strober b, et al. j am acad dermatol. 2020;82(1):117-122. 5. stein gold l, et al. j am acad dermatol. 2018;79(2):287-293. 6. sugarman jl, et al. j drugs dermatol. 2018;17(8):855-861. 7. basra mk, et al. dermatology. 2015;230(1):27-33. author disclosures cl is a consultant for abbvie, amgen, boehringer ingelheim, dermira, eli lilly, janssen, leo pharma, pfizer, sandoz, ucb, and vitae; an investigator for actavis, abbvie, allergan, amgen, boehringer ingelheim, celgene, coherus, cellceutix, corrona, dermira, eli lilly, galderma, glenmark, janssen, leo pharma, merck, novartis, novella, pfizer, sandoz, sienna, stiefel, ucb, and wyeth; and a speaker for abbvie, celgene, novartis, sun pharmaceutical, and eli lilly. lsg has served as investigator/consultant or speaker for ortho dermatologics, leo, dermavant, incyte, novartis, abbvie, pfizer, sun, ucb, arcutis and lilly. el has nothing to disclose. an has received grants/research funding from amgen, celgene, chugai pharma, janssen (johnson & johnson) , maruho, novartis, pfizer, regeneron, and xoma; fellowship funding from abbvie and janssen (johnson & johnson); and has served on advisory boards for janssen (johnson & johnson), abbvie, and amgen. aj is an employee of ortho dermatologics and may hold stock and/or stock options in its parent company. craig leonardi, md1; linda stein gold, md2; edward lain, md, mba3; andrea neimann, md4; abby jacobson, ms, pa-c5 1department of dermatology, st. louis medical school, st. louis, mo; 2henry ford hospital, detroit, mi; 3austin institute for clinical research, austin, tx; 4ronald o. perelman department of dermatology, new york university school of medicine, new york, ny; 5ortho dermatologics*, bridgewater, nj *ortho dermatologics is a division of bausch health us, llc. skin may 2019 volume 3 issue 3 copyright 2018 the national society for cutaneous medicine 212 brief articles terra firma-forme dermatosis, keratotic form jennifer e abdalla, ms,1 allison cruse, md1 neelam patel, md1, robert t brodell, md1 1department of dermatology, university of mississippi medical center, jackson, ms terra firma-forme dermatosis (tffd) is a benign condition that presents as an asymptomatic, dirty-appearing, hyperpigmented plaque. removal of the discoloration with an alcohol pad confirms the diagnosis while serving as an effective treatment for this condition. (1) we present a case of a 60-year-old man with a presentation not previously reported which represents a keratotic form of tffd. a 60-year-old african american man presented for evaluation of a keratotic patch on his right lateral foot just above the right lateral malleolus that had been present for several months. tffd and stucco keratoses were considered on the clinical differential diagnosis. the patient was morbidly obese and suffered from type 2 diabetes mellitus, chronic kidney disease, and hypertension. the patch was mildly pruritic, and scrubbing with a wash cloth, soap, and water led to no improvement. there was no history of footwear rubbing against this area. physical examination revealed confluent, thick, hyperpigmented, “stuck-on”, brown papules clustered on his right lateral ankle (figure 1). no other skin was involved. swabbing the area with several alcohol pads led to no improvement. the keratotic papules had to be removed using the edge of a microscope slide. no bleeding occurred. the crusted debris was sent for histopathologic examination and demonstrated only laminated keratin without evidence of seborrheic/stucco keratosis, verruca vulgaris, or acanthosis nigricans (figure 2). these findings support the diagnosis of tffd. after all keratotic lesions were removed by scraping as noted above, the patient was treated with ammonium lactate 12% lotion twice daily. there has been no recurrence over 6 months. terra firma-forme dermatosis (tffd) is a condition that presents as hyperpigmented patches or plaques that have a dirt-like appearance. a keratotic form of tffd that has not been previously reported is described in this case. the diagnosis and treatment for this condition, the alcohol swab test, did not lead to resolution of the patch in our patient. the keratotic papules had to be removed by using the edge of a microscope slide. this case report serves to provide awareness of this unique, keratotic variant that cannot be removed by wiping with isopropyl alcohol. abstract introduction case report skin may 2019 volume 3 issue 3 copyright 2018 the national society for cutaneous medicine 213 figure 1: right ankle with a patch of keratotic tffd. scraping the right side of the patch cleared this part of the lesion. keratotic debris is noted on the table top. tffd is a benign condition of acquired “dirtlike” plaques. there is a higher incidence in children, however it can affect people of all ages. lesions may involve any area of the body but are typically located on the neck, face, trunk, and ankles. the distribution can be localized, generalized, bilateral, or unilateral. (2). multiple case reports demonstrate large polygonal plate-like brown scales arranged in a mosaic pattern on dermoscopic examination. (3) figure 2: laminated keratin is noted without evidence of seborrheic keratosis, verrucae, or acanthosis nigricans. (h&e, 4x) if a “stone pavement” pattern is observed on dermoscopic exam, this suggests the diagnosis of tffd. (4) the pathophysiology behind this condition may be related to a delay in the maturation of keratinocytes with melanin retention, and an accumulation of sebum, sweat, corneocytes, and microorganisms in locations where hygienic measures are less rigorous. (5) in typical cases, histopathological examination is rarely performed. in this case, however, the failure to clear the lesion with alcohol swabs led to the serendipitous finding that the brown, confluent, keratotic papules could be flicked off with a fingernail under a glove or by rubbing the area with a glass slide. the thick concretions in our case would not respond to alcohol but did resolve with “scraping” with the edge of a glass slide. the appearance of tffd may be concerning to the patient even with the reassurance of its benign nature. diagnosing tffd is important to avoid a biopsy or other workup for localized hyperpigmentation. this case report serves to provide awareness of this unique discussion conclusion skin may 2019 volume 3 issue 3 copyright 2018 the national society for cutaneous medicine 214 hyperkeratotic variant of tffd that cannot be removed by wiping with isopropyl alcohol. conflict of interest disclosures: : robert brodell, m.d. include participation in multi-center clinical trials for galderma laboratories, l.p., novartis, and glaxo smith kline. he serves on the advisory board for intraderm pharmaceuticals. he serves on the editorial boards of journal of the american academy of dermatology, american medical student research journal, practice update dermatology, practical dermatology, journal of the mississippi state medical society, and skin: the journal of cutaneous medicine. jennifer abdalla, allison cruse, and neelam patel have no conflicts of interest. funding: none. corresponding author: robert t brodell, md university of mississippi medical center jackon, ms rbrodell@umc.edu references: 1. pablo fernandez-crehuet, md, phd. dermoscopic signs of duncan’s dirty dermatosis. journal of the american academy of dermatology, 2016;74(5): ab50-ab50. doi:https://doi.org/10.1016/j.jaad.201 6.02.199 2. greywal t, cohen pr. terra firmaforme dermatosis: a report of ten individuals with duncan’s dirty dermatosis and literature review. dermatology practical & conceptual. 2015;5(3):29-33. doi:10.5826/dpc.0503a08. 3. errichetti, e. and stinco, g. dermoscopy in terra firma-forme dermatosis and dermatosis neglecta. int j dermatol, 2017;56:1481-1483. doi:10.1111/ijd.13686 4. fernández-crehuet p, ruiz-villaverde r. terra firma–forme dermatosis. cmaj: canadian medical association journal. 2016;188(4):285. doi:10.1503/cmaj.150075. 5. fernández-crehuet p, ruiz-villaverde r. dirt-like hyperpigmented plaques on the dorsal aspect of both feet. journal of clinical & experimental dermatology research. 2015; 6(1). doi:10.4172/2155-9554.1000257 mailto:rbrodell@umc.edu https://doi-org.ezproxy2.umc.edu/10.1111/ijd.13686 powerpoint presentation • treatment-related aes were few: 16% of tirbanibulin-treated patients and 10% of vehicletreated patients had ≥1 treatment-related ae (mostly transient mild-to-moderate application-site pain and pruritus that did not require treatment). no deaths, discontinuations, or serious aes related to tirbanibulin occurred. • incidence and severity of lsrs greater than baseline were higher with tirbanibulin vs. vehicle (table 2): o for tirbanibulin, the most commonly occurring lsrs were mild to moderate erythema (22% and 63%) and flaking/scaling (26% and 47%), followed by mild crusting (30%) and mild swelling (29%). • 702 subjects were included in the pooled safety population (tirbanibulin n=353; vehicle n=349). treatment compliance was >99%. demographics were similar between treatment groups; most were caucasian males, fitzpatrick skin type ii and median of 6 baseline ak lesions. baseline characteristics are shown in table 1. results todd schlesinger1, neal bhatia2, brian berman3, ayman grada4, albert torra5, david cutler6, mark lebwohl7 1dermatology and laser centre of charleston, charleston, sc, usa; 2therapeutics clinical research, san diego, ca, usa; 3department of dermatology and cutaneous surgery, university of miami miller school of medicine, 4almirall, exton, pa, usa; 5almirall, barcelona, spain;6athenex, inc., buffalo, ny, usa; 7icahn school of medicine at mount sinai, new york, ny, usa. favorable safety profile of tirbanibulin ointment 1% for actinic keratosis: pooled results from two phase iii studies table 1. baseline characteristics • the objective was to report pooled safety data in adults with ak on the face/scalp from two pivotal phase iii randomized, double-blinded, vehicle-controlled, parallel-group studies (kx01-ak-003/kx01-ak-004). objective • safety assessments included local skin reactions (lsrs: erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, erosion/ulceration; scale of 0-3 [absentsevere]) and adverse events (aes) up to day (d) 57. • incidence of maximal post-baseline lsr grades greater than baseline was described by treatment and lsr sign. pooled lsr composite scores (the sum of all 6 lsrs) by visit and treatment were analyzed. tirbanibulin (n=353) vehicle (n=349) mean age (sd), years 69.3 (8.61) 70.2 (9.13) gender: male, n (%) 305 (86) 304 (87) race: white, n (%) 352 (>99) 348 (>99) fitzpatrick skin type, n (%) type i 49 (14) 38 (11) type ii 200 (57) 224 (64) type iii 88 (25) 79 (23) type iv-vi 16 (5) 8 (2) median baseline ak lesion count (min max) 6.0 (4 8) 6.0 (4 8) • writing support was provided by tfs s.l. • this study was sponsored by athenex, inc.. acknowledgements conclusions • pooled data from phase iii studies showed a favorable safety and tolerability profile of tirbanibulin ointment 1% once daily for 5 consecutive days in the treatment of ak on the face or scalp. table 2. maximal post-baseline lsrs by severity (safety population) methods • eligible adult patients with 4-8 clinically visible ak lesions in a 25 cm2 area were randomized 1:1 to receive tirbanibulin ointment 1% or vehicle (5-day once-daily selfapplication). the study design is shown in figure 1. • itt population: included all randomized patients. safety population included all subjects who received at least one dose of tirbanibulin ointment 1% figure 1. design of both studies • regarding composite lsr scores, lsr peaked on d8 with tirbanibulin with a maximum mean composite lsr score of 4.1, decreased significantly by d15, and resolved by d29d57. by d29 and d57, mean composite lsr scores were similar between tirbanibulin (0.6 and 0.4, respectively) and vehicle groups (0.6 and 0.5) (figure 2 and figure 3). • no significant difference was observed in mean composite lsr score in patients less and above 65 year old (maximum mean lsr: 4) 40th annual fall clinical dermatology conference, october 29 november 1, 2020 • tirbanibulin is a first-in-class, novel inhibitor of tubulin polymerization and associated with disruption of src kinase signaling for actinic keratosis (ak). • no cases of contact sensitization or phototoxicity were observed in two phase i studies (kx01-ak-006/kx01-ak-008). synopsis table 3. treatment-related adverse events up to day 57 of incidence ≥2% by treatment location subgroups (face/scalp) figure 2. lsr composite score from baseline to day 57 (tirbanibulin, itt population) once daily for 5 days day 57 1 year day 57 1 year tirbanibulin n=175 350 patients per trial vehicle n=175 1-year follow-up phase (only for patients with complete clearance at day 57) 57-day phase once daily for 5 days • there were no differences in treatment-related aes according to age, gender, and baseline ak lesions. overall incidence of treatment-related aes was slightly higher for face (17% and 11%) than scalp subjects (13% and 7%) in the tirbanibulin and vehicle groups, respectively (table 3). ak, actinic keratosis; sd, standard deviation safety population (n=702) n (%) tirbanibulin (n=353) vehicle (n=349) erythema mild 76 (22) 98 (28) moderate 223 (63) 20 (6) severe 22 (6) 0 flaking/scaling mild 92 (26) 86 (25) moderate 166 (47) 33 (9) severe 31 (9) 1 (<1) crusting mild 107 (30) 31 (9) moderate 50 (14) 8 (2) severe 7 (2) 0 swelling mild 102 (29) 15 (4) moderate 32 (9) 1 (<1) severe 2 (<1) 0 vesicles/pustules mild 25 (7) 3 (<1) moderate 2 (<1) 0 severe 2 (<1) 0 erosions/ulcers mild 32 (9) 10 (3) moderate 9 (3) 0 severe 0 0 the length of the box represents the interquartile range (the distance between the 25th and 75th percentiles). the symbol in the box interior represents the group mean. the horizontal line in the box interior represents the group median. safety population (n=702) n (%) tirbanibulin (n=353) vehicle (n=349) face scalp face scalp number of subjects with any treatmentrelated aes 41 (17) 15 (13) 27 (11) 8 (7) application site pain 26 (11) 9 (8) 9 (4) 2 (2) application site pruritus 23 (10) 9 (8) 18 (8) 3 (3) figure 3. evolution of moderate and severe lsr from baseline to day 57 moderate lsr severe lsr m e a n c o m p o s it e l s r s c o re 12 11 10 9 8 7 6 5 4 3 2 1 0 day 1 day 5 day 8 day 15 day 29 day 57 visit day skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 302 in-depth reviews a review of auto-injector pen safety and preventative strategies eduardo rodriguez bsa, morgan l. arnold bsa, michael g. wilkerson mdb auniversity of texas medical branch at galveston, school of medicine, galveston, tx buniversity of texas medical branch at galveston, department of dermatology, galveston, tx auto-injectors, in this case defined as autoinjector pens, have recently seen a rise in reports of injuries caused by accidental or improper self-injection. there has been 15, 190 incidents from unintentional epinephrine auto-injectors alone reported from 1994 to 2007 to us poison control centers. sixty percent of these were reported from 2003 to 2007.1 more recently, from 2013 to 2014, there were a total of 6,806 reported cases of unintentional epinephrine auto-injector injuries.2 however, auto-injectors are not only limited to epinephrine as they can contain a variety of drugs and biological products such as adalimumab (humira), etanercept (enbrel), and secukinumab (cosentyx) to name a few. despite an increase in reporting, the true incidence of auto-injector injuries is unknown. the goal of this article is to provide the reader with an overview of auto-injector pen handling guidelines, commonly encountered injuries, common barriers to proper handling, as well as possible preventative strategies. this article endeavors to increase awareness of possible consequences of mishandling auto-injectors and what steps can be taken to reduce injuries for both patients, caregivers, and health professionals in the future. after a patient had presented to clinic with features consistent with anaphylaxis, a 55year-old dermatologist tried to administer a dose of epinephrine using an auto-injector pen before transferring the patient to the emergency department. whilst trying to administer the medication, he suffered from an accidental auto-injection into the volar introduction case report reports of auto-injector pen injuries have increased over the past decade. however, the true incidence of these injuries is unknown. we present the case of an accidental digital selfinjection by a dermatologist whilst he was trying to administer the medication to a patient presenting with anaphylaxis as an example of a typical auto-injector injury. additionally, we discuss safety issues, commonly reported injuries of accidental self-injection, and review the safety guidelines for use of a common auto-injector pen. finally, we explore common barriers to proper auto-injector handling and suggested preventative strategies in order to decrease injuries caused by auto-injectors. abstract skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 303 aspect of his right thumb. the dermatologist then experienced severe pain, tachycardia, diaphoresis, and subsequent blanching of his right thumb. he immediately pulled out the needle from his thumb and found the tip to be bent after hitting the bone. this prevented the entire dose of epinephrine from being injected. a few minutes later his thumb became pale, cool, and numb from the tip down to the base. subsequent radiograph showed no bone abnormalities. after a literature search, he decided to wait for symptoms to resolve on their own. six hours after the initial injury, his thumb began to re-perfuse and regained some of its color as well as sensation. eight hours after the initial injury, he returned to baseline without any lasting pain, numbness, or blanching. the current epipen epinephrine auto-injector package insert emphasizes safe use guidelines to avoid lacerations, embedded needles, and accidental injections. first, it stresses the importance of never pressing or placing any digit over the orange tip of the injector, which is the end that dispenses the injection needle; instead, the hand should encircle the injector circumferentially during injection, with the thumb overlapping the index finger.3,4 this prevents the user from accidental auto-injection should they unknowingly hold the auto-injector upsidedown. it also warns against removing the blue safety cap before the user is ready to inject; this cap should be pulled straight off rather than bent or twisted off. to prevent lacerations and embedded needles, the insert now advises caregivers to firmly hold the leg of young children during injection administration. finally, the insert warns anyone who experiences accidental selfinjection to visit their nearest emergency department immediately for evaluation and treatment.4 epinephrine auto-injector devices now have several safety features to prevent injuries to patients and caregivers. the blue safety cap is designed to prevent the injection needle from deploying prematurely and must be removed for injection to proceed. the orange tip contains the injection needle and exists to cover the needle once the needle is removed from the patient’s thigh. moreover, patients are strongly encouraged to carry epinephrine auto-injectors in sets of two, in case one dose proves to be sub-therapeutic or the administrator of the first dose accidentally self-injects.4 despite the potentially life-saving effects of epinephrine auto-injector use, certain safety hazards have been shown to affect users. perhaps the most studied safety concern in the literature is accidental injection. despite an increasing number of reports of accidental digital auto-injection, a retrospective cohort study of 6 texas poison control centers over six years showed that only four cases of ischemic sequelae resulted from the 365 calls regarding accidental epinephrine injection. in all four cases, the patient responded to vasodilatory therapy and symptoms resolved without serious complications.1,5 of the 127 cases of digital auto-injection examined in the study in which the patients had follow-up, the most common of these temporary symptoms were pain (68%), blanching (42%), discoloration (17%), and numbness (16%); a small minority experienced ecchymosis (3.1%), ischemia (3.1%), and decreased capillary refill (1.6%).5 auto injector safety guidelines & features safety issues skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 304 long term sequelae of accidental autoinjector pen injections are rare but do occur. a 2007 literature review of 59 case reports of accidental epinephrine auto-injection found four instances of prolonged neuropraxia following the injury, one of which took 10 weeks to resolve. this same patient experienced documented ischemia reperfusion pain. interestingly, the same study showed no cases of digital necrosis or improved outcomes in cases where vasodilators such as terbutaline or phentolamine were administered.6 other safety hazards of auto-injector use include laceration (usually occurring when a caregiver attempts to inject a squirming child), embedded needles, and perforation of bone with the needle.3,4,7 these incidents are reported relatively infrequently, mostly occur in children, and require further study to determine potential prevention techniques and specific treatment guidelines. despite manufacturer’s guidelines being available for the use of pen auto-injectors, injuries continue to occur. therefore, research has focused on finding preventable contributing factors to auto-injector injuries as well as suggesting additional strategies to minimize injuries. one of the primary barriers to the safe use of auto-injectors is the lack of knowledge and proper training on part of the prescribing physicians, patients, and caregivers on the correct handling and use of auto-injector pens.8-11 with a provider being unable to demonstrate the proper use of an auto-injector, successfully educating both patients and caregivers becomes unlikely. in fact, in one study looking at 100 physicians consisting of both residents and fellows/consultants, only 2 of them were able to demonstrate all steps of an auto-injector pen administration correctly. 57% of them did not hold the pen in place for >5 seconds, 21% failed to apply enough pressure to activate, and 16% had a self-injection into the thumb. of these same physicians, 45 had previously prescribed epinephrine auto-injectors with just 3 of them having demonstrated its use to parents and children.8 furthermore, when studies have looked at parents and children who have been prescribed an epinephrine auto-injector they have also consistently shown a lack of knowledge on proper use.9,10 in a study with 49 enrolled parents, only 24% were able to recall all the steps to correctly administer their child’s medication. half of the enrollees did not remember to remove the cap before using the device and to hold the device in place for several seconds.9 low rates of physicians providing their patients with written materials and availability of placebo trainers can further contribute to the patient’s inability to properly use autoinjectors.10,11 proper training can help diminish both injuries and improper use of auto-injector pens. when physicians were given both hands-on training along with a lecture on anaphylaxis with re-demonstration of an epinephrine auto-injector, the correct use of auto-injectors increased from 23.3% before training to 74.2% after it. the rate at which the most common mistakes occurred significantly decreased after training, although the ranking did not change. of note, holding the auto-injector in place for >5 seconds increased from 48.3% to 82.1% after training while accidental self-injection into thumb decreased from 36.4% to 7.3%.12 another possible barrier to minimizing injuries is a lack of an intuitive design of autoinjectors. however, making small modifications to the design of auto-injector barriers & preventative strategies skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 305 pens can greatly decrease the rate at which injuries occur when using auto-injectors.13,14 for instance, in a particular study where researchers modified an epinephrine autoinjector by placing a yellow arrow pointing to the black injection tip as well as changing the gray safety cap to red; the rate at which injuries occurred was lower in the group with the modified auto-injector when compared to the group with an unmodified version. with a total of 164 interns participating in the study split into two groups, 22.6% of those in the unmodified group demonstrated correct administration of the epinephrine autoinjector compared to 65% in the modified group. additionally, 45.2% of the participants in the unmodified group had presumptive unintentional injection injuries while only 5% of participants in the modified group did.13 therefore, further efforts should be made by manufacturers to provide both clinicians and patients with safer and more intuitive designs. figure 1. (a) older epinephrine auto-injector model showing a black needle-end and a bent needle after accidental self-injection by a dermatologist. (b) newer color-coded epinephrine auto-injector model showing a blue safety cap and an orange needle-end. some have even suggested that by having a more intuitive design, correct use of autoinjectors can be improved even when used by individuals with minimal training.15 another suggestion that has been made is to change the order of steps for administration by placing the needle’s end to the outer midthigh first, before removing the safety cap.16 these could help reduce the contribution of a lack of proper training in the occurrence of autoinjector injuries, although this is yet to be further investigated. after reviewing the types of injuries caused by auto-injectors, common contributing factors, and preventative strategies, we believe further emphasis should be placed on early thorough resident training and autoinjector design modifications. with a combination of proper training and design modifications, achieving a decrease in the rate of auto-injector injuries and improper handling appears possible. this has the potential to not only prevent mishandling injuries, but to also improve medication compliance for diseases managed with prescribed auto-injectors and outcomes of patients presenting with anaphylaxis by performing prompt medication administration. in an effort to reduce improper handling, design changes made to the epipen since its first introduction to the market included colorcoding both ends of the auto-injector by having a blue safety cap and an orange needle-end (figure 1). other auto-injectors types like auvi-q, an epinephrine autoinjector, features electronic voice instructions that guides users through the process of epinephrine injection administration.17 despite the recent design changes seen in epinephrine auto-injectors, further discussion skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 306 improvements to aid in the intuitive use of auto-injectors can still be made. we encourage the reader to take time to familiarize themselves with the variety of auto-injectors used in their respective practice by reading the manufacturer’s guidelines and by practicing with placebo trainers if available. furthermore, properly demonstrating the correct administration steps of auto-injectors to patients when prescribing, and subsequently reinforcing these steps during follow-up visits, should remain a vital component of patient education to aid in medication compliance and reduction of injuries. conflict of interest disclosures: none. funding: none. corresponding author: eduardo a. rodriguez, b.s. department of dermatology university of texas medical branch at galveston, school of medicine galveston, tx 77555 edarodri@utmb.edu references: 1. simons, f. e., edwards, e. s., read, e. j., jr., clark, s., & liebelt, e. l. (2010). voluntarily reported unintentional injections from epinephrine autoinjectors. the journal of allergy and clinical immunology, 125(2), 419-423. doi: 10.1016/j.jaci.2009.10.056. 2. anshien, m., rose, s. r., & wills, b. k. (2016). unintentional epinephrine auto-injector injuries. american journal of therapeutics. doi:10.1097/mjt.0000000000000541 3. posner, l. s., & camargo, c. a. (2017). update on the usage and safety of epinephrine auto-injectors, 2017. drug, healthcare and patient safety, 9, 9-18. doi:10.2147/dhps.s121733 4. epipen (epinephrine injection, usp) auto-injector and its authorized generic. https://www.epipen.com/en/. accessed february 20, 2018. 5. muck, a., bebarta, v., borys, d., & morgan, d. (2007). six years of acute unintentional epinephrine digital injections: lack of ischemia or significant systemic effects. academic emergency medicine, 14(5 supplement 1). doi:10.1197/j.aem.2007.03.1267 6. fitzcharles-bowe, c., denkler, k., & lalonde, d. (2006). finger injection with high-dose (1:1,000) epinephrine: does it cause finger necrosis and should it be treated? hand, 2(1), 5-11. doi:10.1007/s11552-006-9012-4 7. schintler, m. v., arbab, e., aberer, w., spendel, s., & scharnagl, e. (2005). accidental perforating bone injury using the epipen autoinjection device. allergy, 60(2), 259-260. doi:10.1111/j.13989995.2004.00620.x 8. mehr, s., robinson, m. and tang, m. (2007), doctor – how do i use my epipen?. pediatric allergy and immunology, 18: 448–452. doi:10.1111/j.13993038.2007.00529.x 9. gold, m. s., & sainsbury, r. (2000). first aid anaphylaxis management in children who were prescribed an epinephrine autoinjector device (epipen). journal of allergy and clinical immunology, 106(1), 171-176. doi:10.1067/mai.2000.106041 10. sicherer, s. h., forman, j. a., & noone, s. a. (2000). use assessment of selfadministered epinephrine among food-allergic children and pediatricians. pediatrics, 105(2), 359362. doi:10.1542/peds.105.2.359 11. grouhi, m., alshehri, m., hummel, d., & roifman, c. m. (1999). anaphylaxis and mailto:edarodri@utmb.edu skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 307 epinephrine auto-injector training: who will teach the teachers?. journal of allergy and clinical immunology, 104(1), 190-193. doi:10.1016/s00916749(99)70134-x 12. arga, m., bakirtas, a., catal, f., derinoz, o., harmanci, k., razi, c. h., turktas, i. (2011). training of trainers on epinephrine autoinjector use. pediatric allergy and immunology, 22(6), 590593. doi:10.1111/j.13993038.2011.01143.x 13. bakirtas, a., arga, m., catal, f., derinoz, o., demirsoy, m. s., & turktas, i. (2011). make-up of the epinephrine autoinjector: the effect on its use by untrained users. pediatric allergy and immunology, 22(7), 729-733. doi:10.1111/j.13993038.2011.01195.x 14. arga, m., bakirtas, a., topal, e., yilmaz, o., karagol, i. h., demirsoy, m. s., & turktas, i. (2012). effect of epinephrine autoinjector design on unintentional injection injury. allergy and asthma proceedings, 33(6), 488-492. doi:10.2500/aap.2012.33.3609 15. gosbee, l. l. (2004). nuts! i can’t figure out how to use my life-saving epinephrine auto-injector! the joint commission journal on quality and safety, 30(4), 220-223. doi:10.1016/s1549-3741(04)30024-9 16. kränke, b., reiter, h., kainz, j. t., & arbab, e. (2011). how to improve the safety of adrenaline (epinephrine) autoinjectors. journal of allergy and clinical immunology, 127(6), 1645. doi:10.1016/j.jaci.2011.02.009 17. auvi-q | home. about auvi-q | auvi-q. https://www.auvi-q.com/about-auviq/. accessed february 20, 2018. introduction results conclusions methods objective subjects study design assessments tm weber,1 ce arrowitz,1 u scherdin,2 am schoelermann,2 a filbry2 1beiersdorf inc, wilton, ct, usa; 2beiersdorf ag, hamburg, germany a moisturizing spray ointment to help alleviate dry skin symptoms associated with atopic eczema, psoriasis, and xerosis figure 1. figure 2. figure 3. figure 4. figure 5. 55% 6% 35% 2% atopic eczema xerosis psoriasis ichthyosis n=80 2.29 1.61 0.34 0.86 0.51 0.13 0 0.5 1.0 1.5 2.0 2.5 dryness scaling cracks m ea n c lin ic al g ra d in g s co re * * * obs=aquaphor ointment body spray *p<0.0001 vs baseline n=80 baseline end of study 0 20 40 60 severe/ very severe moderate slight none severe/ very severe moderate slight none severe/ very severe moderate slight none 0 20 40 60 0 25 50 75 reduction in dryness reduction in scaling reduction in cracks n=70 n=20 end of study 0.59 1.39 1.39 1.1 0.15 0.81 0.41 0.39 0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 burning erythema itching tightness m ea n c lin ic al g ra d in g s co re * * * * obs=aquaphor ointment body spray *p<0.0001 vs baseline n=80 baseline end of study reduction in itching reduction in erythema 0 20 40 60 0 20 40 60 % o f su b je ct s % o f su b je ct s n=62 n=57 reduction in burning reduction in tightness obs=aquaphor ointment body spray mean duration of treatment=16.2 days % o f su b je ct s % o f su b je ct s 0 20 40 60 0 20 40 60 80 n=35 n=52 severe/ very severe moderate slight none severe/ very severe moderate slight none severe/ very severe moderate slight none severe/ very severe moderate slight none progression to reduced symptom severity baseline end of study p p fc17posterbeiersdorfwebermoisturizingspray.pdf � � � � � � ± � � ≤ � � � � � � � � � � � follow-up 1st pdt cycle pdt-1 pdt-2 1 week pdt-3 pdt-4 1 week 2nd pdt cycle 3 m 6 m 24 m 60 m 2020 if lesions remain 0 10 20 30 40 50 60 70 80 � � � � 12 m 36 m follow-up � � � � fc17posterbiofronteramortonbf200alaphotodynamictx.pdf s2008053 fall cdc 2020 nguyen.indd presented at the 40th annual fall clinical dermatology conference (fall cdc 2020); virtual congress; october 29 – november 01, 2020. background • dupilumab is a fully human monoclonal antibody1,2 that blocks the shared receptor component for interleukin-4 and interleukin-13 and has a demonstrated safety profile and sustained efficacy in adult and pediatric patients (aged ≥ 6 years) with moderate-to-severe atopic dermatitis (ad)3–6 • there is currently a paucity of information on patients who receive dupilumab in a real-world setting • we present baseline data from a real-world registry of adult ad patients, initiating commercial dupilumab treatment for ad per approved prescribing information objective • to report patient and family history of ad, and ad treatments taken before treatment initiation with dupilumab in patients from the prose registry atopic dermatitis (ad) disease history with ad treatment history in a cohort of ad patients treated with dupilumab from a real-world registry (prose) tien q. nguyen1, hermenio lima2, lindsey finklea3, haixin zhang4, daniel richman5, andrew korotzer4, shikha bansal4 1first oc dermatology, fountain valley, ca, usa; 2mcmaster university, hamilton, on, canada; 3rfsa dermatology, san antonio, tx, usa; 4regeneron pharmaceuticals, inc., tarrytown, ny, usa; 5sanofi genzyme, cambridge, ma, usa conclusions • family history of ad was common in patients enrolled in this real-world registry • comorbid ocular diseases were frequently reported, including one-fifth of patients reporting seasonal allergic conjunctivitis • all patients had received other ad treatments before initiating dupilumab, and almost all used ≥ 1 ad medication in the past year • half of the patients in prose also received ≥ 1 topical and ≥ 1 systemic treatment during their life references: 1. macdonald le, et al. proc natl acad sci u s a. 2014;111:5147-52. 2. murphy aj, et al. proc natl acad sci u s a. 2014;111:5153-8. 3. blauvelt a, et al. lancet. 2017;389:2287-303. 4. de bruin-weller m, et al. br j dermatol. 2018;178:1083-101. 5. simpson el, et al. n engl j med. 2016;375:2335-48. 6. beck la, et al. am j clin dermatol. 2020;21:567-77. acknowledgments: research sponsored by sanofi and regeneron pharmaceuticals, inc. clinicaltrials.gov identifier: nct03428646. medical writing/editorial assistance provided by toby leigh bartholomew, phd, of excerpta medica, funded by sanofi genzyme and regeneron pharmaceuticals, inc. disclosures: nguyen tq: abbvie, almirall, amgen, biogen, bms, celgene, corrona, gsk, janssen, eli lilly, merck, novartis, pfizer, regeneron pharmaceuticals, inc., sanofi, sun pharma, ucb – investigator, consultant, and/or speaker. lima h: sanofi – investigator, advisor, and speaker. finklea l: eli lilly, janssen, novartis, regeneron pharmaceuticals, inc., sanofi – advisor. zhang h, korotzer a, bansal s: regeneron pharmaceuticals, inc. – employees and shareholders. richman d: sanofi genzyme – employee, may hold stock and/or stock options in the company. methods study design • prose (nct03428646) is an ongoing (initiated: april 2018), multicenter, longitudinal, prospective, up-to-5years observational registry in the usa and canada characterizing dupilumab-treated ad patients in a realworld setting • baseline data were recorded at the time of entry into the registry analysis • data presented here are from the first interim analysis set of adult patients receiving dupilumab (data cutoff: july 2019) • all analyses are descriptive without imputation for missing values results patients and demographics • 315 patients were enrolled (table 1) – approximately half of the patients were female, and 60% white – mean age of patients was 42.5 years and the mean duration of ad was 19.7 years patient ad history • 35% of patients had a family history of ad (table 2) • 54.0% of patients reported one or more type 2 inflammatory comorbidities in the 12 months prior to dupilumab initiation, including allergic rhinitis which was reported in 32.7% of patients (table 3) results (cont.) table 1. baseline demographics and disease characteristics. n = 315 age, mean (sd), years 42.5 (16.99) female sex, n (%) 174 (55.2) race, n (%) white 187 (59.4) black or african american 56 (17.8) asian 51 (16.2) othera 7 (2.2) not reported 14 (4.4) height, mean (sd), cm 168.03 (10.27) weight, mean (sd), kg 79.72 (20.60) duration of ad, mean (sd), years 19.7 (17.30) age at ad diagnosis, mean (sd), years 23.7 (23.13) easi, mean (sd) 16.90 (13.36) peak pruritus nrs, mean (sd) 6.9 (2.30) aincludes american indian or alaskan native and native hawaiian or other pacific islander. easi, eczema area and severity index; n1, number of patients with assessment; nrs, numerical rating scale; sd, standard deviation. table 2. family history of ad. n = 315 patients with family history of ad, n (%) 110 (34.9) relationship of family member who had ad, n (%) mother 40 (12.7) father 27 (8.6) sibling 41 (13.0) grandparent 13 (4.1) other 32 (10.2) table 3. proportion of patients with type 2 inflammatory comorbiditiesa in the 12 months before dupilumab initiation. n = 315 any type 2 inflammatory comorbidities, n (%) 170 (54.0) allergic rhinitis 103 (32.7) asthma 81 (25.7) allergic conjunctivitis 62 (19.7) food allergies 41 (13.0) chronic urticaria 17 (5.4) a ≥ 5% of patients. table 4. ocular history over the past 12 months.a n = 315 n (%) no. of days of active condition, mean (sd) seasonal allergic conjunctivitis 60 (19.0) 82.6 (109.84) dry eye 29 (9.2) 121.3 (149.01) perennial allergic conjunctivitis 17 (5.4) 198.4 (160.11) ophthalmic herpes simplex 5 (1.6) 3.0 (3.67) blepharitis 4 (1.3) 89.0 (141.59) aconditions reported in > 1% of patients. table 5. ad treatment history (life-long recall). n (%) n = 315 ≥ 1 prior ad medication 315 (100.0) previous use of ≥ 1 topical (tci/tcs/pde4 inhibitors), and 1 systemic corticosteroid or 1 systemic non-steroidal immunosuppressant 160 (50.8) previous use of systemic corticosteroids 129 (41.0) previous use of systemic non-steroidal immunosuppressants 53 (16.8) methotrexate 32 (10.2) cyclosporine 27 (8.6) mycophenolate 10 (3.2) azathioprine 3 (1.0) all values are n (%). pde4, phosphodiesterase-4; tci, topical calcineurin inhibitors; tcs, topical corticosteroids. table 6. ad treatment history (12-month recall). n = 315 n (%) mean number of days ≥ 1 ad medication 294 (93.3) n/a tcs 286 (90.8) 178.9 tci 113 (35.9) 94.6 pde4 inhibitors 62 (19.7) 66.4 phototherapy 23 (7.3) 59.7 systemic corticosteroids 114 (36.2) 39.6 systemic non-steroidal immunosuppressants 44 (14.0) 150.1 methotrexate 24 (7.6) 111.6 cyclosporine 22 (7.0) 160.5 mycophenolate 6 (1.9) 40.5 azathioprine 2 (0.6) 75.0 n/a: not applicable. • the reported history of ocular conditions is shown in table 4 – seasonal allergic conjunctivitis was most commonly (19.0%) reported for a mean  (sd) of 82.6 (109.84) days in the past year ad treatment history • 50.8% of the patients received ≥ 1 topical and 1 systemic medication for ad (table 5) – 41.0% used systemic corticosteroids; methotrexate (10.2%) was the most commonly used systemic nonsteroidal immunosuppressant • in the year prior to enrollment, most patients used topical corticosteroids (90.8%), followed by systemic corticosteroids (36.2%) and tcis (35.9%) (table 6) – the average duration of use for these medications was 178.9, 39.6, and 94.6 days, during the past year, respectively skin december 2018 volume 2 supplemental issue copyright 2018 the national society for cutaneous medicine 95 rising derm stars the microbiome in preadolescent acne: assessment and prospective analysis on the influence of benzoyl peroxide jusleen ahluwalia md1, lawrence f eichenfield md1 1department of dermatology, uc san diego, san diego, ca background/objectives: the pathogenesis of preadolescent acne has not been well studied, and it is uncertain if propionibacterium acnes is a predominant organism in the microbiome in this age group.1-4 the aim of this study was to analyze the microbiome of preadolescent females, and to assess if benzoyl peroxide (bp) impacts the microbiome. methods: the study enrolled females, aged 7-12 years old, with evidence of at least six acneiform lesions who had not been previously treated with prescription acne products, bp, or had recently received oral antibiotics. subjects’ skin surface of forehead, cheeks, nose, chin, left retroauricular crease and extruded contents of a comedonal lesion were sampled at baseline. subjects utilized bp 4% wash for 6 to 8 weeks and returned for skin surface sampling and extraction collection. microbiome analysis was performed using 16s ribosomal rna gene amplicon sequencing on all swab and lesional extraction samples. results: 51 subjects were enrolled with a median iga score of 2 (mild). changes in microbiome diversity were associated with increasing age and number of acneiform lesions (p=0.001) (figure 1). p. acnes had higher abundances on forehead and nose, as opposed to cheeks and chin (p=0.009). bacterial diversity (alpha diversity) of the skin microbiome was comparable between preadolescent at baseline and after treatment with benzoyl peroxide (figure 2). conclusion: this is the first large assessment characterizing female acne microbiome in early and late preadolescence. results show that preadolescent acne can vary in its microbial profile, reflecting surrounding changes associated with the onset of puberty. although benzoyl peroxide use was associated with decreased acne counts, its effect on microbial diversity was not demonstrated in our study. figure 1: bar plot of bacterial species according to number of acne lesions. skin december 2018 volume 2 supplemental issue copyright 2018 the national society for cutaneous medicine 96 figure 2: phylogenetic diversity in visit 1 (pretreatment) and visit 2 (post-treatment). boxes indicate the 25th percentile, median, and 75th percentile. outliers are represented by open dots. whiskers show the minimum and maximum ranges. references: references: 1. dréno b, araviiskaia e, berardesca e, gontijo g, sanchez viera m, xiang lf, martin r, bieber t. microbiome in healthy skin, update for dermatologists. j eur acad dermatol venereol. 2016 dec;30(12):2038-2047. 2. lucky aw, biro fm, huster ga, leach ad, morrison ja, ratterman j. acne vulgaris in premenarchal girls. an early sign of puberty associated with rising levels of dehydroepiandrosterone. arch dermatol. 1994 mar;130(3):308-14. 3. oh j, conlan s, polley ec, segre ja, kong hh. shifts in human skin and nares microbiota of healthy children and adults. genome med. 2012 oct 10;4(10):77. 4. coughlin cc, swink sm, horwinski j, sfyroera g, bugayev j, grice ea, yan ac. the preadolescent acne microbiome: a prospective, randomized, pilot study investigating characterization and effects of acne therapy. pediatr dermatol. 2017 nov;34(6):661-664. internal use todd schlesinger, md1; leon kircik, md2; april armstrong, md3; brian berman, md, phd4; neal bhatia, md5; james del rosso, do6; mark lebwohl, md2; vishal a. patel, md7; darrell rigel, md, ms2; siva narayanan, phd8; volker koscielny, md9 ismail kasujee phd9 1clinical research center of the carolinas, charleston, sc, usa; 2mount sinai icahn school of medicine, new york, ny, usa; 3keck school of medicine, university of southern california, los angeles, ca, usa; 4university of miami miller school of medicine, miami, fl, usa; 5therapeutics clinical research, san diego, ca, usa; 6jdr dermatology research/thomas dermatology, las vegas, nv, usa; 7george washington school of medicine and health sciences, washington, dc, usa; 8avant health llc, bethesda, md, usa; 9almirall sa, barcelona, spain investigator global assessment (iga) of actinic keratosis (ak) among patients administered tirbanibulin in real-world community practices across the u.s., and clinician likelihood to consider tirbanibulin again for future ak treatments (proak study) introduction: actinic keratosis (ak) are epidermal lesions with potential to progress to squamous cell carcinomas if left untreated.1 aks have also been shown to negatively affect emotional functioning and skin-related quality of life of patients.2 the primary objective of the analysis was to evaluate iga success at week-8, and clinician-reported likelihood to consider tirbanibulin again for future treatments, among patients with aks administered tirbanibulin in community practices across the u.s. methods: a single-arm, prospective cohort study (proak: nct05260073) was conducted among adult patients with aks on the face or scalp who were newly initiated with tirbanibulin treatment in real-world community practices in the u.s, as part of usual care. patients and clinicians completed surveys and clinical assessments at baseline, week-8 (timeframe for main endpoints) and week-24. clinicians assessed ak responses using an iga on a five-point adjectival response scale of 0 (completely cleared), 1 (partially cleared), 2 (moderately cleared), 3 (minimally cleared) and 4 (not cleared). iga success was defined as achieving an iga score of 0 or 1 at week-8. clinicians also reported their likelihood to reuse tirbanibulin treatment for their patients, as a surrogate measure of satisfaction with the treatment. results: a total of 290 ak patients completed the study assessments at week-8. at week-8, proportion of patients with completely/partially cleared ak (approximately 75-100% clearance of ak lesions in the treated area, iga 1/0) was 73.79%; moderately cleared (iga 2) was 17.24%, and minimally cleared/not cleared (iga 3/4) was 8.97%. correspondingly, iga success in this cohort of patients treated with tirbanibulin was 73.79%. proportion of patients for whom clinicians noted that they would ‘somewhat or very likely’ consider tirbanibulin treatment again, if need arises, was 85.17%, with 7.59% reporting a neutral response, and 7.24% reporting ‘somewhat or very unlikely’ to consider treatment with tirbanibulin again. conclusion: the majority of patients with aks using tirbanibulin experienced iga success at week-8, and a majority of clinicians reported their desire to consider tirbanibulin again to treat ak lesions for their patients. references: 1. j drugs dermatol. 2021;20(8):888-893; 2. br j dermatol. 2013;168(2):277-283. synopsis conclusions • within the study cohort of adult patients with aks administered once-daily tirbanibulin treatment for 5-days as part of usual care, a majority of patients (73.79%) with aks experienced iga success at week-8. • for majority of patients (85.17%), clinicians reported their desire to consider tirbanibulin again to treat ak lesions, if need arises. • the demonstrated effectiveness and the safe and tolerable profile of once-daily tirbanibulin treatment, and the associated clinician willingness to reconsider tirbanibulin treatment for their patients in the future, highlights the benefits associated with this novel therapeutic option for optimal management of aks. sponsored by almirall, s.a. methods • a single-arm, prospective cohort study (proak) was conducted among adult patients with aks on the face or scalp who were newly initiated with once-daily tirbanibulin treatment (5-day course) in real-world community practices in the u.s, as part of usual care. • a total of 300 subjects were enrolled from 32 community practices across the u.s. • patients and clinicians completed surveys and clinical assessments at baseline, week-8 (timeframe for main endpoints) and week-24, concerning safety and effectiveness of tirbanibulin. • at week-8, clinicians assessed ak responses (compared to baseline) using an iga on a five-point adjectival response scale, as follows: • 0 (completely cleared), 1 (partially cleared), 2 (moderately cleared), 3 (minimally cleared) and 4 (not cleared). • iga success was defined as achieving an iga score of 0 or 1 at week-8. • at week-8, clinicians reported their likelihood to consider tirbanibulin again (for each of their patients) if need arises in the future, on a fivepoint adjectival response scale, as follows: • 1 (very unlikely), 2(somewhat unlikely), 3 (neutral), 4 (somewhat likely), 5 (very likely). • iga, iga success, and clinician-reported ‘likelihood to consider tirbanibulin again’ were analyzed ‘as observed’, using week-8 data. objective • the primary objective of the analysis was to evaluate iga success at week-8, and clinician-reported likelihood to consider tirbanibulin again for future treatments, among patients with aks administered tirbanibulin in community practices across the u.s. results • proak study (nct05260073) was initiated in 2022, with more than 75% of the study patients treated with tirbanibulin between april and august of 2022. • out of 300 enrolled patients, a total of 290 patients with aks completed the study assessments at week-8, and hence included in the analyses. • overall, in 77.93% and 33.79% of study patients (not mutually exclusive), ak lesions on their face and scalp respectively were treated with tirbanibulin. • all patients (100%) completed their 5-day once-daily treatment course. • ten patients were not included in the week-8 analyses: 1 patient had missing data, and 9 patients were discontinued from the study due to patient voluntary withdrawal of consent or lost to follow-up. • no discontinuations were related to adverse drug reactions (adrs), and there were no serious adrs reported at week-8. table 1: baseline patient characteristics n=290 age, mean years [min, max] 66.30 [30.00, 90.00] gender, % femalemale 31.38 68.62 primary health insurance, % private insurance medicaid medicare uninsured 41.72 3.10 53.79 1.38 history of skin cancer, % 61.72 fitzpatrick skin type, % type i type ii type iii type iv type v 7.59 71.38 18.62 1.38 1.03 baseline patient selfreported skin-texture, % dry smooth rough bumpy scaly blistering peeling 39.66 47.59 19.66 18.62 35.17 0.34 6.21 baseline severity of skin photodamage in ak affected area, % absent mild moderate severe 1.03 21.38 56.55 20.34 73.79% 17.24% 8.97% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% completely / partially cleared moderately cleared minimally / not cleared p ro po rti on o f p at ie nt s at w ee k8 figure 1: majority of patients who were administered tirbanibulin at baseline achieved iga success at week-8 7.24% 7.59% 85.17% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% very / somewhat unlikely neutral somewhat / very likely p ro po rti on o f p at ie nt s at w ee k8 figure 2: for majority of patients, clinicians reported their desire to consider tirbanibulin again table 2: site characteristics (n=32) current workplace: private, office-based practice, % 100 total number of board-certified dermatologists in the clinic/practice, mean 3.53 number of patients with aks managed by the clinic in a given month, mean 136.34 number of years practicing dermatology, mean 15.66 iga success n = 290 n = 290 skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 72 in-depth reviews review of suicide and depression in psoriasis and management of suicide warnings in patients treated with psoriasis drugs emily lebowitz ba1, mark lebwohl md2 1weill cornell medical college, new york, ny 2department of dermatology, icahn school of medicine at mount sinai, new york, ny multiple studies have found that patients with psoriasis are at risk for depression.(1-6) a recent meta-analysis reported the prevalence of major depression to be 9% to 28% among patients with this disease.(2) the authors of a population-based cohort study in the united kingdom found that patients with psoriasis had an increased risk of depression, anxiety and suicidality,(1) and the authors of a cohort study in the usa found that psoriasis was associated with major depression even after adjusting for demographic factors and medical comorbidities such as cardiovascular disease.(4) while the dermatologic symptoms of pruritus, burning and pain can independently have a negative impact on overall quality of life,(7) the psychosocial impact of psoriasis has increasingly received greater attention. patients have reported feeling stigmatized and embarrassed due to their physical appearance,(4, 8) and patients’ perception of their disease severity, regardless of the objective extent of skin involvement, may correlate with depression risk.(1) introduction patients with psoriasis are thought to be at increased risk of depression, anxiety and suicidality predominantly as a result of the psychosocial impact of this disease. studies have shown that the pro-inflammatory cytokines that are elevated in psoriasis and targeted by biologics have also been identified in patients with depression. it is therefore thought that anti-cytokine therapies may improve patients’ quality of life not only by reducing their disease burden but also by modulating the inflammatory pathways implicated in depression. while depression is mentioned in the package inserts of brodalumab and apremilast, only brodalumab has a black box warning requiring discussion of suicidality prior to prescribing the drug. in clinical trials, the majority of patients receiving brodalumab experience a reduction in symptoms of depression and anxiety. the package insert for brodalumab points out that no causal association has been established between brodalumab and suicide, and the fda-mandated risk evaluation and mitigation strategies (rems) program for brodalumab takes only minutes to complete. brodalumab and apremilast may therefore be considered for patients in whom depression is caused by psoriasis, provided that patients and their providers have a mutual understanding of the risks and benefits of these therapies and the rems program is followed. abstract skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 73 studies have demonstrated that patients treated with tnf-alpha inhibitors (etanercept, infliximab, and adalimumab), interleukin (il)17 inhibitors (ixekizumab), and il-12/il-23 inhibitors (ustekinumab) for psoriasis can experience notable improvement in symptoms of depression and anxiety.(9-13) brodalumab, an il-17 receptor antibody, and apremilast, an oral medication that inhibits phosphodiesterase 4 (pde4), have also been shown to improve symptoms of depression in patients with psoriasis.(14) (15) however, the package inserts for these two therapies mention depression, suicidal ideation and behavior (sib) or suicide. in this article, we review the data that led to the concern for psychiatric adverse events during treatment with brodalumab and apremilast and we summarize the evidence for their clinical efficacy. we also summarize data on the psychiatric effects of biologic therapies overall on patients with psoriasis and discuss the possible connection between psoriasis, depression, and systemic inflammation. il-17a, il-17c and il-17f are cytokines that promote inflammation in psoriasis, and il-17producing t cells have been localized to the dermis of psoriatic skin lesions.(16, 17) brodalumab is a fully human anti-il-17 receptor monoclonal antibody which has demonstrated success in treating patients with moderate-to-severe plaque psoriasis in randomized clinical trials.(14, 18) in a 12week, phase 2, dose-ranging study,(18) patients were randomized to receive placebo or subcutaneous injection of brodalumab. patients in the treatment group received brodalumab either at a dose of 70 mg, 140 mg, or 210 mg on day 1 and at weeks 1, 2, 4, 6, 8, and 10, or at a dose of 280 mg on day 1 and at weeks 4 and 8. mean improvements in psoriasis area-and-severity index (pasi) scores were 86.3%, 85.9%, and 76.0% among those receiving 210 mg, 140 mg, and 280 mg of brodalumab, respectively, in comparison to 16% among those receiving placebo. in a phase 3, double-blind, randomized, placebo-controlled study of brodalumab (amagine-1),(14) patients in both treatment groups (140 mg and 210 mg) were found to have significantly greater improvements in their pasi scores. additionally, a greater proportion of patients receiving brodalumab as opposed to placebo reported resolution of psoriasis symptoms such as itching, burning, redness and pain. depression and suicidality: 3066 patients with psoriasis were treated with brodalumab over the course of the following clinical trials: a phase 2, randomized, doubleblinded, placebo-controlled, dose-ranging study, an open-label extension of this phase 2 study, and three phase 3, double-blind, randomized controlled trials (amagine1[nct01708590], amagine-2 [nct0170863], amagine 3 [nct01708629]) along with their open-label long-term extensions.(14, 19) in a pooled analysis of these 5 clinical trials,(19) 1.0% of patients receiving placebo and 0.8% of patients receiving brodalumab reported depression during the 12-week controlled treatment period. during the 52-week activecontrolled treatment period, sib occurred in four patients (0.11%) treated with brodalumab. two patients completed suicide, one attempted suicide, and one engaged in intentional self-injury. cumulatively, over the course of the controlled treatment periods and open-label extensions of these studies, sib in the form of intentional self-injury, unspecified suicidal behavior, suicide attempt or completed suicide occurred in 15 (0.16%) patients. six patients (0.07%) attempted suicide and four (0.04%) completed suicide— brodalumab skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 74 all four were men ranging from 39 to 59 years of age. one of these events was later deemed indeterminate in the columbia classification algorithm for suicide assessment review.(19) across the phase 2 and 3 clinical trials for brodalumab, the risk of sib during brodalumab treatment was found to be higher among those with a prior history of depression or suicidality.(19) after approximately 260 weeks of follow-up, including the period after which treatment was discontinued, 3.21% of patients with a history of suicidality exhibited suicidal behavior in comparison to 0.20% of patients with no history of suicidality. approach to the patient starting brodalumab: due to the observed events of suicidal ideation and completion during treatment with brodalumab in clinical trials, this therapy is available in the united states only through a risk evaluation and mitigation strategy (rems) program. both prescribers and pharmacies must be certified with the rems program. the fda requires that patients register with rems only once; this process takes a short time to complete (less than 5 minutes) and requires a very brief explanation. patients must also sign a patient-prescriber agreement form prior to starting brodalumab that indicates they are aware of the risks associated with the medication and that they will seek medical attention should feelings of depression or suicidality develop. a definitive association between brodalumab and suicidality has not been established,(19, 20) and the fda points out no causal relationship between brodalumab and suicide. however, brodalumab is the only biologic therapy with a black box requirement figure 1: boxed-warning regarding suicidal ideation and behavior in the prescribing information for brodalumab. for providers to discuss suicide and depression with patients initiating treatment (figure 1). the rems program, in addition to this black box warning, are two safety precautions that ensure this very effective treatment can continue to be offered to patients with psoriasis. additional biologic therapies targeting the il17 cytokine family are available for patients with psoriasis. secukinumab, a human monoclonal anti-il-17a antibody, and ixekizumab, a recombinant, humanized monoclonal antibody that also selectively targets il-17a, are two biologics that have proven efficacious for the treatment of moderate-to-severe plaque psoriasis.(21, 22) in a phase 3, double-blind, 52-week trial investigating the efficacy of secukinumab versus etanercept, 77.1% of patients receiving 300 mg of subcutaneous secukinumab (administered once weekly for 5 weeks, then every 4 weeks) achieved reductions in pasi scores of at least 75%, in comparison to 44.0% of those receiving 50 mg of etanercept (administered twice weekly secukinumab & ixekizumab skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 75 for 12 weeks, then once weekly) and 4.9% of those receiving placebo.(21) in a phase 3 clinical trial investigating ixekizumab in the treatment of moderate-to-severe psoriasis, 89.1% of patients receiving 80 mg of subcutaneous ixekizumab (administered twice weekly for 12 weeks following a starting dose of 160 mg) achieved 75% or greater reductions in pasi scores in comparison to 3.9% of patients in the placebo group. (23) in a pooled analysis of 10 clinical trials of secukinumab, the most commonly reported adverse effects were nasopharyngitis, headaches, and upper respiratory tract infections.(24) these studies did not report an association between secukinumab and increased risk of sib or depression. ixekizumab has also not been linked to an increased risk of depression or suicidal behavior and has been demonstrated to improve symptoms of depression in patients with psoriasis. (12) if suicidal ideation and depression are of particular concern when starting a patient on an anti-il-17 therapy, it is important to recognize that alternative options such as secukinumab and ixekizumab may be considered. apremilast is an oral medication that inhibits phosphodiesterase 4 (pde4) and leads to the downregulation of tumor necrosis factor (tnf)-alpha, il-12, and il-23, proinflammatory cytokines that are elevated in psoriasis.(25) in a phase 2b, randomized, placebo-controlled, dose-ranging trial of apremilast for the treatment of moderate-tosevere psoriasis,(26) a greater proportion of patients receiving apremilast versus placebo achieved significant improvement, as determined by 75% reduction from baseline pasi scores. in a phase 3 randomized controlled trial of apremilast in patients with moderate-to-severe plaque psoriasis (esteem 1),(27) a significantly higher percentage of patients randomized to apremilast versus placebo achieved 75% or greater reduction in psoriasis severity. additionally, the majority of patients initially in the placebo group and re-randomized to apremilast also achieved significant reduction in disease severity. apremilast was further demonstrated to be effective in biologic-naïve patients with moderate plaque psoriasis involving 5 to 10% of the body surface area, with improvements sustained after 52 weeks of follow-up.(28) depression and suicidality: a total of 832 patients were treated with apremilast across two phase 3 clinical trials.(29) at baseline, 13.4% of patients in the placebo group and 13.7% of patients in the treatment group reported depression (respectively). during the placebo-controlled phase of the trial, patient-reported depression occurred in 12/832 (1.4%) patients being treated with apremilast and 2/418 (0.5%) patients receiving placebo. at week 16 of the trial, patient-reported depression was noted to be higher in the apremilast group; psychiatric adverse events (specifically depression) in this group did not continue to increase over subsequent weeks. at the completion of the study there had been one suicide attempt and no completed suicides in the apremilast group. one patient in the placebo arm of esteem 1 attempted and completed suicide. in additional retrospective cohort studies of apremilast for the treatment of psoriasis, patient-reported rates of depression and mood lability have ranged from 0.8% to 3.9%.(30-32) none of these studies have reported instances of suicidal attempts or completions. apremilast skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 76 figure 2: depression specified as a precaution in prescribing apremilast. approach to the patient starting apremilast: in the prescribing information for apremilast, depression is listed under “warnings and precautions” (figure 2). at week 16 of the phase 3 placebo-controlled trials, 1.3% of patients treated with apremilast reported feelings of depression in comparison to 0.4% of patients treated with placebo. one patient (0.1%) experienced treatment-limiting depression that led to discontinuation of apremilast, while none of the patients in the placebo group discontinued treatment as a result of depression. due to this imbalance of patient-reported depression at this point in the trial, it is therefore recommended that the risks and benefits of initiating apremilast be weighed, particularly in patients with a history of psychiatric comorbidities or suicidal behavior. as with brodalumab, patients starting apremilast should be appropriately counseled to seek medical assistance should they develop symptoms of depression or suicidal ideation. systemic inflammation in psoriasis may play a role in the development of depression,(33) as pro-inflammatory cytokines that are elevated in psoriasis-such as il-17, il-23, and tnf-alpha-have also been identified in patients with depression.(34) inflammatory marker levels are increased in the central nervous system (cns) of individuals with depression and suicidal behavior,(35) indicating that a pro-inflammatory state may be implicated in the pathophysiology of depressive symptoms. this connection between inflammation and depression has been illustrated in studies of anti-depressant medications. one study found that bupropion, a commonly used antidepressant, decreased levels of tnf-alpha synthesis in mice,(36) and another study found that combination treatment with bupropion and a selective serotonin reuptake inhibitor (ssri) was more effective in patients with higher baseline levels of il17.(37) anti-cytokine treatments have been found to decrease symptoms of depression in those with inflammatory diseases.(38) tnf-alpha antagonists in particular have been shown to reduce symptoms of depression in patients with psoriasis.(11, 39) one study demonstrated that a higher proportion of patients receiving etanercept, as opposed to placebo, achieved at least 50% improvement in symptoms of depression.(40) therapies targeting il-12, il-17 and il-23 have also been shown to impact mental health. greater improvements in symptoms of anxiety and depression, as measured by the hospital anxiety and depression scale (hads), were observed in patients receiving ustekinumab (il-12/il-23 inhibitor) and guselkumab (il-23 inhibitor) versus those receiving placebo.(9, 41) ixekizumab also demonstrated efficacy in this regard, leading to the remission of depression in 40% of patients who fit criteria psoriasis, depression & inflammatory cytokines skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 77 for moderately severe depression at baseline.(12) while patients with psoriasis are understood to be at increased risk of depression, the influence of systemic treatment itself on depression has not been well characterized. recently, patients in the psoriasis longitudinal assessment and registry (psolar)(42) who were being treated with biologics, other systemic therapies (such as methotrexate or cyclosporine), or phototherapy were assessed for the development of depressive symptoms.(43) the biologics ustekinumab, adalimumab, etanercept, and infliximab were included in this study. the incidence rate of depression ranged from 2.62% to 3.53% among those receiving biologics, while the incidence was 5.85% and 5.70% among those receiving phototherapy and conventional systemic therapy, respectively. a total of 21 patients demonstrated suicidal ideation and behavior, with 3 men completing suicide. of the 11 patients who attempted or completed suicide, 7 were receiving biologic therapy and 8/11 (73%) had a history of depression at the time of enrollment in the study. the incidence rate of suicidal ideation, suicide attempt, or suicide completion was 43 per 100,000 patient years within the entire cohort; the incidence rate of suicide among patients with psoriasis is reported to be 90 per 100,000 patient years.(1) the authors of this study concluded that biologic therapy is correlated with a lower risk of depressive symptoms, in comparison to conventional systemic therapy, among patients with moderate-tosevere psoriasis. given the unclear connection between suicidality and non-tnfalpha biologics, additional studies might further elucidate this risk. the negative impact of psoriasis on patients’ quality of life is well established and has been explored at length in the literature. while patients with psoriasis are reported to have higher rates of depression, anxiety and suicidality, successful response to treatment has been correlated with a positive impact on mental health and overall quality of life. therapies that target the pro-inflammatory cytokines elevated in psoriasis have demonstrated substantial clinical efficacy across a number of clinical trials and should therefore be considered for those with moderate-to-severe or recalcitrant disease. while adverse psychiatric events have been reported during treatment with brodalumab and apremilast, a causal association between these therapies and suicide has yet to be established. it is nevertheless evident that patients with known psychiatric conditions or prior histories of suicidal behavior may be at slightly increased risk of adverse psychiatric effects when starting a new biologic such as brodalumab. it is therefore imperative that careful medical histories are obtained in order to closely monitor patients and to determine whether alternative therapies should be considered. conflict of interest disclosures: none. funding: none. corresponding author: mark g. lebwohl, md icahn school of medicine at mount sinai new york, ny lebwohl@aol.com references: 1. kurd sk, troxel ab, crits-christoph p, gelfand jm. the risk of depression, anxiety, and suicidality in patients with conclusion psychiatric effects of systemic therapies mailto:lebwohl@aol.com skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 78 psoriasis: a population-based cohort study. arch dermatol. 2010;146(8):891-5. 2. dowlatshahi ea, wakkee m, arends lr, nijsten t. the prevalence and odds of depressive symptoms and clinical depression in psoriasis patients: a systematic review and meta-analysis. j invest dermatol. 2014;134(6):1542-51. 3. dommasch ed, li t, okereke oi, li y, qureshi aa, cho e. risk of depression in women with psoriasis: a cohort study. br j dermatol. 2015;173(4):975-80. 4. cohen be, martires kj, ho rs. psoriasis and the risk of depression in the us population: national health and nutrition examination survey 20092012. jama dermatol. 2016;152(1):739. 5. egeberg a, thyssen jp, wu jj, skov l. risk of first-time and recurrent depression in patients with psoriasis a population-based cohort study. br j dermatol. 2018. 6. wu jj, penfold rb, primatesta p, fox tk, stewart c, reddy sp, et al. the risk of depression, suicidal ideation and suicide attempt in patients with psoriasis, psoriatic arthritis or ankylosing spondylitis. j eur acad dermatol venereol. 2017;31(7):116875. 7. devrimci-ozguven h, kundakci tn, kumbasar h, boyvat a. the depression, anxiety, life satisfaction and affective expression levels in psoriasis patients. j eur acad dermatol venereol. 2000;14(4):267-71. 8. patel n, nadkarni a, cardwell la, vera n, frey c, feldman sr. psoriasis, depression, and inflammatory overlap: a review. am j clin dermatol. 2017;18(5):613-20. 9. langley rg, feldman sr, han c, schenkel b, szapary p, hsu mc, et al. ustekinumab significantly improves symptoms of anxiety, depression, and skin-related quality of life in patients with moderate-to-severe psoriasis: results from a randomized, doubleblind, placebo-controlled phase iii trial. j am acad dermatol. 2010;63(3):45765. 10. krishnan r, cella d, leonardi c, papp k, gottlieb ab, dunn m, et al. effects of etanercept therapy on fatigue and symptoms of depression in subjects treated for moderate to severe plaque psoriasis for up to 96 weeks. br j dermatol. 2007;157(6):1275-7. 11. menter a, augustin m, signorovitch j, yu ap, wu eq, gupta sr, et al. the effect of adalimumab on reducing depression symptoms in patients with moderate to severe psoriasis: a randomized clinical trial. j am acad dermatol. 2010;62(5):812-8. 12. griffiths cem, fava m, miller ah, russell j, ball sg, xu w, et al. impact of ixekizumab treatment on depressive symptoms and systemic inflammation in patients with moderate-to-severe psoriasis: an integrated analysis of three phase 3 clinical studies. psychother psychosom. 2017;86(5):260-7. 13. feldman sr, gottlieb ab, bala m, wu y, eisenberg d, guzzo c, et al. infliximab improves health-related quality of life in the presence of comorbidities among patients with moderate-to-severe psoriasis. br j dermatol. 2008;159(3):704-10. 14. papp ka, reich k, paul c, blauvelt a, baran w, bolduc c, et al. a prospective phase iii, randomized, double-blind, placebo-controlled study of brodalumab in patients with moderateto-severe plaque psoriasis. br j dermatol. 2016;175(2):273-86. skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 79 15. thaci d, kimball a, foley p, poulin y, levi e, chen r, et al. apremilast, an oral phosphodiesterase 4 inhibitor, improves patient-reported outcomes in the treatment of moderate to severe psoriasis: results of two phase iii randomized, controlled trials. j eur acad dermatol venereol. 2017;31(3):498-506. 16. johnston a, fritz y, dawes sm, diaconu d, al-attar pm, guzman am, et al. keratinocyte overexpression of il-17c promotes psoriasiform skin inflammation. j immunol. 2013;190(5):2252-62. 17. lowes ma, kikuchi t, fuentes-duculan j, cardinale i, zaba lc, haider as, et al. psoriasis vulgaris lesions contain discrete populations of th1 and th17 t cells. j invest dermatol. 2008;128(5):1207-11. 18. papp ka, leonardi c, menter a, ortonne jp, krueger jg, kricorian g, et al. brodalumab, an anti-interleukin-17receptor antibody for psoriasis. n engl j med. 2012;366(13):1181-9. 19. lebwohl mg, papp ka, marangell lb, koo j, blauvelt a, gooderham m, et al. psychiatric adverse events during treatment with brodalumab: analysis of psoriasis clinical trials. j am acad dermatol. 2018;78(1):81-9.e5. 20. chiricozzi a, romanelli m, saraceno r, torres t. no meaningful association between suicidal behavior and the use of il-17a-neutralizing or il-17rablocking agents. expert opin drug saf. 2016;15(12):1653-9. 21. langley rg, elewski be, lebwohl m, reich k, griffiths ce, papp k, et al. secukinumab in plaque psoriasis-results of two phase 3 trials. n engl j med. 2014;371(4):326-38. 22. gordon kb, blauvelt a, papp ka, langley rg, luger t, ohtsuki m, et al. phase 3 trials of ixekizumab in moderate-to-severe plaque psoriasis. n engl j med. 2016;375(4):345-56. 23. gordon kb, colombel jf, hardin ds. phase 3 trials of ixekizumab in moderate-to-severe plaque psoriasis. n engl j med. 2016;375(21):2102. 24. blauvelt a. safety of secukinumab in the treatment of psoriasis. expert opin drug saf. 2016;15(10):1413-20. 25. schafer ph, parton a, gandhi ak, capone l, adams m, wu l, et al. apremilast, a camp phosphodiesterase4 inhibitor, demonstrates antiinflammatory activity in vitro and in a model of psoriasis. br j pharmacol. 2010;159(4):842-55. 26. papp k, cather jc, rosoph l, sofen h, langley rg, matheson rt, et al. efficacy of apremilast in the treatment of moderate to severe psoriasis: a randomised controlled trial. lancet. 2012;380(9843):738-46. 27. papp k, reich k, leonardi cl, kircik l, chimenti s, langley rg, et al. apremilast, an oral phosphodiesterase 4 (pde4) inhibitor, in patients with moderate to severe plaque psoriasis: results of a phase iii, randomized, controlled trial (efficacy and safety trial evaluating the effects of apremilast in psoriasis [esteem] 1). j am acad dermatol. 2015;73(1):37-49. 28. stein gold l, bagel j, lebwohl m, jackson jm, chen r, goncalves j, et al. efficacy and safety of apremilast in systemicand biologic-naive patients with moderate plaque psoriasis: 52week results of unveil. j drugs dermatol. 2018;17(2):221-8. 29. crowley j, thaçi d, joly p, peris k, papp ka, goncalves j, et al. long-term safety and tolerability of apremilast in patients with psoriasis: pooled safety analysis for ≥156 weeks from 2 phase 3, skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 80 randomized, controlled trials (esteem 1 and 2). j am acad dermatol. 2017;77(2):310-7.e1. 30. ighani a, georgakopoulos jr, shear nh, walsh s, yeung j. long-term 52-week trends in apremilast safety outcomes for treatment of psoriasis in clinical practice: a multicentre, retrospective case series. br j dermatol. 2018. 31. lee eb, amin m, egeberg a, wu jj. adverse events associated with apremilast use and withdrawal for psoriasis in a real-world setting. j eur acad dermatol venereol. 2018;32(10):e393-e4. 32. papadavid e, rompoti n, theodoropoulos k, kokkalis g, rigopoulos d. real-world data on the efficacy and safety of apremilast in patients with moderate-to-severe plaque psoriasis. j eur acad dermatol venereol. 2018;32(7):1173-9. 33. tohid h, aleem d, jackson c. major depression and psoriasis: a psychodermatological phenomenon. skin pharmacol physiol. 2016;29(4):220-30. 34. patel n, nadkarni a, cardwell la, vera n, frey c, patel n, et al. psoriasis, depression, and inflammatory overlap: a review. am j clin dermatol. 2017;18(5):613-20. 35. koo j, marangell lb, nakamura m, armstrong a, jeon c, bhutani t, et al. depression and suicidality in psoriasis: review of the literature including the cytokine theory of depression. j eur acad dermatol venereol. 2017;31(12):1999-2009. 36. brustolim d, ribeiro-dos-santos r, kast re, altschuler el, soares mb. a new chapter opens in anti-inflammatory treatments: the antidepressant bupropion lowers production of tumor necrosis factor-alpha and interferongamma in mice. int immunopharmacol. 2006;6(6):903-7. 37. jha mk, minhajuddin a, gadad bs, greer tl, mayes tl, trivedi mh. interleukin 17 selectively predicts better outcomes with bupropion-ssri combination: novel t cell biomarker for antidepressant medication selection. brain behav immun. 2017;66:103-10. 38. kappelmann n, lewis g, dantzer r, jones pb, khandaker gm. antidepressant activity of anti-cytokine treatment: a systematic review and meta-analysis of clinical trials of chronic inflammatory conditions. mol psychiatry. 2018;23(2):335-43. 39. kannan s, heller mm, lee es, koo jy. the role of tumor necrosis factor-alpha and other cytokines in depression: what dermatologists should know. j dermatolog treat. 2013;24(2):148-52. 40. tyring s, gottlieb a, papp k, gordon k, leonardi c, wang a, et al. etanercept and clinical outcomes, fatigue, and depression in psoriasis: double-blind placebo-controlled randomised phase iii trial. lancet. 2006;367(9504):29-35. 41. gordon kb, armstrong aw, han c, foley p, song m, wasfi y, et al. anxiety and depression in patients with moderate-to-severe psoriasis and comparison of change from baseline after treatment with guselkumab vs. adalimumab: results from the phase 3 voyage 2 study. j eur acad dermatol venereol. 2018;32(11):1940-9. 42. kimball ab, leonardi c, stahle m, gulliver w, chevrier m, fakharzadeh s, et al. demography, baseline disease characteristics and treatment history of patients with psoriasis enrolled in a multicentre, prospective, disease-based registry (psolar). br j dermatol. 2014;171(1):137-47. skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 81 43. strober b, gooderham m, de jong emgj, kimball ab, langley rg, lakdawala n, et al. depressive symptoms, depression, and the effect of biologic therapy among patients in psoriasis longitudinal assessment and registry (psolar). j am acad dermatol. 2018;78(1):70-80. abstract • introduction: investigator’s global assessment modified 2011 (iga mod 2011) is a more robust measure of psoriasis clearance than traditional iga and physician’s global assessment scales. secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin-17a, has significant efficacy in moderate-tosevere psoriasis and psoriatic arthritis, demonstrating a rapid onset of action and sustained responses with a favorable safety profile. this post hoc analysis evaluates iga mod 2011 0 (clear) and iga (mod 2011) 0/1 (clear or almost clear) response rates over 1 year following treatment with secukinumab pooled from 4 phase 3 trials (erasure, fixture, feature, and juncture) involving patients with moderate-to-severe plaque psoriasis. • methods: secukinumab (300 mg or 150 mg) or placebo was administered at baseline, weeks 1, 2 and 3, and then every 4 weeks from week 4 to 48. in fixture, etanercept (50 mg) was administered twice weekly for 12 weeks, then once weekly. • results: of 2396 patients, 691, 692, 326, and 687 were randomized to secukinumab 300 mg, secukinumab 150 mg, etanercept, and placebo, respectively. significantly more patients receiving secukinumab 300 mg compared with placebo achieved iga (mod 2011) 0/1 (clear or almost clear) responses as early as week 2 (after 2 doses of secukinumab) and iga (mod 2011) 0 (clear) responses as early as week 8 (after 5 doses of secukinumab). a significantly greater proportion of patients achieved iga (mod 2011) 0/1 (clear or almost clear) responses at week 12 (after 6 doses of secukinumab) with secukinumab 300 mg (65.0%) and secukinumab 150 mg (51.4%) compared with etanercept (27.2%) and placebo (2.2%; p <0.0001 for both secukinumab doses vs. etanercept and placebo). iga (mod 2011) 0/1 (clear or almost clear) responses were sustained at week 52 for secukinumab 300 mg (64.9%), secukinumab 150 mg (47.4%), and etanercept (37.2%; p <0.0001 for secukinumab 300 mg vs. etanercept). at week 12, a significantly greater proportion of patients achieved iga (mod 2011) 0 (clear) responses with secukinumab 300 mg (29.9%) and secukinumab 150 mg (15.1%) compared with etanercept (5.3%) and placebo (0.3%; p <0.0001 for both secukinumab doses vs. etanercept and placebo). iga (mod 2011) 0 (clear) responses were sustained at week 52 for secukinumab 300 mg (37.8%), secukinumab 150 mg (21.6%), and etanercept (9.6%; p <0.0001 for secukinumab 300 mg vs. etanercept). • conclusion: secukinumab 300 mg provides early and sustained complete or near-complete skin clearance in up to 65% of patients with moderate-to-severe plaque psoriasis. introduction • secukinumab, a fully human monoclonal antibody that inhibits interleukin (il)-17a, has been shown to have significant efficacy in the treatment of moderate-to-severe psoriasis and psoriatic arthritis, demonstrating sustained high levels of efficacy with a favorable safety profile1–3 • psoriasis clearance shortly after treatment initiation is important so that patients can experience improved quality of life early during treatment – greater levels of psoriasis clearance are associated with a greater quality-of-life benefit4 • iga modified 2011 (iga mod 2011) is a more robust measure of psoriasis clearance than traditional iga and physician’s global assessment scales5 – for example, evaluation of induration requires ‘‘no thickening’’ for a score of 1 with iga mod 2011 compared with ‘‘minimal plaque elevation’’ in other scales5 • in this post hoc analysis, we evaluated iga mod 2011 0 (clear) and iga mod 2011 0/1 (clear or almost clear) response rates over 1 year of secukinumab treatment, pooled from 4 phase 3 trials (erasure, fixture, feature, and juncture) of patients with moderate-to-severe plaque psoriasis methods • this pooled analysis included data from 4 phase 3 randomized, double-blinded, clinical trials of patients with moderate-to-severe plaque psoriasis (details of these trials have been previously published) – erasure (nct01365455)1 – fixture (nct01358578)1 – feature (nct01555125)6 – juncture (nct01636687)7 • in all trials, patients received subcutaneous (sc) secukinumab (300 mg or 150 mg) or placebo at baseline, weeks 1, 2, and 3, and then every 4 weeks from week 4 to 48 (figure 1) – in the fixture study, etanercept 50 mg was administered as per label twice weekly from baseline to week 12, then once weekly to week 51 – at week 12, patients initially randomized to placebo who did not achieve a psoriasis area and severity index (pasi) response of 75 were re-randomized to secukinumab 300 mg or secukinumab 150 mg figure 1. study design secukinumab 300 mg* secukinumab 300 mg† secukinumab 150 mg† q4wk q4wk secukinumab 150 mg* treatment q4wk treatment q4wk placebo* placebo‡ 50 mg qw*etanercept 50 mg biw fixture only induction baseline maintenance follow-up week 48week 12week 8 week 52 week 60 ra r *treatment or placebo at baseline and weeks 1, 2, 3, 4, and 8 to week 48; in fixture, etanercept or placebo biw to week 12 †treatment at weeks 12, 13, 14, and 15 ‡placebo at weeks 12, 13, 14, and 15, then q4wk from week 16 until week 48; in fixture, etanercept placebo qw to week 51 biw, twice weekly; qw, every week; q4wk, every 4 weeks; pasi, psoriasis area and severity index; r, randomization; ra, subjects on placebo who did not achieve a pasi 75 response were re-randomized • in each study, the co-primary endpoints were pasi 75 and iga mod 2011 responses of 0/1 (clear or almost clear) at week 12 – an iga mod 2011 score of 0 indicates no signs of psoriasis, although postinflammatory hyperpigmentation may be present. an iga mod 2011 score of 1 indicates almost clear skin, with no thickening, normal-to-pink coloration, and no-to-minimal focal scaling5 – iga scales correlate well with pasi5 • missing values were analyzed by nonresponder imputation in this analysis • demographic and baseline disease characteristics were well balanced across treatment groups (table 1) table 1. patient demographic and baseline disease characteristics parameter secukinumab 300 mg sc (n = 691) secukinumab 150 mg sc (n = 692) etanercept (n = 326) placebo (n = 692) sex (male), n (%) 477 (69.0) 485 (70.1) 232 (71.2) 484 (69.9) age (years), mean (sd) range 44.9 (13.3) 18–83 45.1 (13.4) 18–83 43.8 (13.0) 18–79 44.7 (12.8) 18–82 race/ethnicity, n (%) white asian black other 505 (73.1) 129 (18.7) 9 (1.3) 48 (6.9) 499 (72.1) 129 (18.6) 13 (1.9) 51 (7.4) 219 (67.2) 74 (22.7) 0 33 (10.1) 509 (73.6) 121 (17.5) 13 (1.9) 49 (7.1) height (cm), mean (sd) range 171.2 (9.6) 145.0–198.5 171.3 (10.2) 145.0–197.0 171.2 144.0–198.0 171.6 (10.2) 141.0–200.7 weight (kg), mean (sd) range 86.6 (23.2) 45.0–219.1 86.6 (23.2) 43.1–215.0 84.6 (20.5) 42.0–175.6 86.0 (22.6) 42.0–191.9 bmi (kg/m2), mean (sd) range 29.4 (6.9) 17.4–67.4 29.4 (7.0) 16.5–79.7 28.7 (5.9) 15.4–58.3 29.1 (6.9) 16.2–71.2 pasi, mean (sd) range 22.7 (9.4) 11.2–72.0 22.8 (10.0) 12.0–69.6 23.2 (9.8) 12.0–54.5 22.5 (9.7) 10.6–72.0 iga modified 2011 score, n (%) 3 (moderate disease) 4 (severe disease) 436 (63.1) 255 (36.9) 439 (63.4) 253 (36.6) 195 (59.8) 131 (40.2) 424 (61.3) 268 (38.7) time since first psoriasis diagnosis (years), mean (sd) range 17.0 (12.0) 0.5–61.5 17.9 (12.5) 0.5–69.0 16.4 (12.0) 0.6–57.2 17.5 (12.2) 0.5–68.1 previous exposure to systemic psoriasis therapy (yes), n (%) 438 (63.4) 447 (64.6) 214 (65.6) 420 (60.7) previous exposure to biologic systemic psoriasis therapy (yes), n (%) 146 (21.1) 161 (23.3) 45 (13.8) 147 (21.2) previous exposure to nonbiologic systemic psoriasis therapy (yes), n (%) 373 (54.0) 393 (56.8) 204 (62.6) 363 (52.5) bmi, body mass index; iga, investigator’s global assessment; pasi, psoriasis area and severity index; sc, subcutaneous; sd, standard deviation • iga mod 2011 0/1 (clear or almost clear) response rates to week 52 are presented in figure 2 – significantly greater improvements with secukinumab 300 mg compared with placebo were observed beginning at week 2, after 2 doses of secukinumab (4.1% versus 0.4%; p < 0.0001) – at week 12 (after 6 doses of secukinumab), significantly more patients achieved iga mod 2011 0/1 responses with secukinumab 300 mg (65.0%) and secukinumab 150 mg (51.4%) compared with etanercept (27.2%) and placebo (2.2%; p < 0.0001 for both secukinumab doses versus etanercept and versus placebo) – iga mod 2011 0/1 response rates were sustained at week 52 and were significantly greater for secukinumab 300 mg compared with etanercept (p < 0.0001) • in patients achieving iga 0/1 at any time up to 12 weeks, median time to a 50% decrease from baseline in mean pasi was 2.6 weeks with secukinumab 300 mg and 3.1 weeks with secukinumab 150 mg (figure 3) figure 2. iga mod 2011 0/1 (clear/almost clear) response rates over time 0 40 60 80 100 0 1 2 3 52 ig a 0 /1 r es po nd er s (% ) week 20 4 8 12 16 20 24 28 32 36 40 44 48 secukinumab 150 mg (n = 692) placebo (n = 692) secukinumab 300 mg (n = 691) etanercept (n = 326) † 65.0 64.9 † 51.4 47.4 27.2 2.2 37.2 *4.1 1.6 0.3 0.4 *p < 0.0001 for secukinumab 300 mg versus placebo †p < 0.0001 for both secukinumab doses versus etanercept and placebo iga mod 2011 0/1, investigator’s global assessment, 2011 modified version, improvement to scores of 0 or 1 (clear or almost clear skin) figure 3. speed of response in iga mod 2011 0/1 (clear/ almost clear) responders at any time up to 12 weeks -100 -80 -60 -40 -20 0 0 1 2 3 4 weeks c ha ng e fr om b as el in e in m ea n p a s i s co re (% ) 8 12 bootstrap median time to 50% reduction in mean pasi score, with 95% ci secukinumab 300 mg secukinumab 150 mg 2.6 (2.5–2.7) 3.1 (2.9–3.2) a repeated-measures, mixed-effects model was used to analyze the mean percent change from baseline in pasi the median time to a 50% reduction in mean pasi was estimated from parametric bootstrap samples with the use of linear interpolation between time points ci, confidence interval; iga mod 2011 0/1, investigator’s global assessment, 2011 modified version, improvement to scores of 0 or 1 (clear or almost clear skin); pasi, psoriasis area and severity index • iga mod 2011 0 (clear) response rates to week 52 are presented in figure 4 – beginning at week 8 (after 5 doses of secukinumab), significantly greater response rates were observed with secukinumab 300 mg (17.9%) and secukinumab 150 mg (9.3%) compared with etanercept (1.5%) and placebo (0.3%; p < 0.0001 for both secukinumab doses versus etanercept and placebo) figure 4. iga mod 2011 0 (clear) response rates over time 0 40 60 80 100 0 52 ig a 0 r es po nd er s (% ) week 20 4 8 12 16 20 24 28 32 36 40 44 48 secukinumab 150 mg (n = 692) placebo (n = 692) secukinumab 300 mg (n = 691) etanercept (n = 326) 1 2 3 *29.9 *17.9 *9.3 1.5 37.8 *15.1 21.6 5.3 0.3 0.3 9.6 *p < 0.0001 for both secukinumab doses versus etanercept and placebo iga mod 2011 0, investigator’s global assessment, 2011 modified version, improvement to scores of 0 (clear skin) – similarly, significantly more patients achieved iga mod 2011 0 (clear) responses at week 12 with secukinumab 300 mg (29.9%) and secukinumab 150 mg (15.1%) compared with etanercept (5.3%) and placebo (0.3%) (p < 0.0001 for both secukinumab doses versus etanercept and placebo) – iga mod 2011 0 (clear) response rates were sustained at week 52 and were significantly greater for secukinumab 300 mg compared with etanercept (37.8% versus 9.6%, respectively; p < 0.0001) • in patients achieving iga mod 2011 0 at any time up to 12 weeks, median time to a 50% decrease from baseline in mean pasi was 2.3 weeks with secukinumab 300 mg and 2.6 weeks with secukinumab 150 mg (figure 5) figure 5. speed of response in iga mod 2011 0 (clear) responders at any time up to 12 weeks -100 -80 -60 -40 -20 0 0 1 2 3 4 weeks c ha ng e fr om b as el in e in m ea n p a s i s co re (% ) 8 12 bootstrap median time to 50% reduction in mean pasi score, with 95% ci secukinumab 300 mg secukinumab 150 mg 2.6 (2.3–2.8) 2.3 (2.1–2.4) a repeated-measures, mixed-effects model was used to analyze the mean percent change from baseline in pasi the median time to a 50% reduction in mean pasi was estimated from parametric bootstrap samples with the use of linear interpolation between time points ci, confidence interval; iga mod 2011 0, investigator’s global assessment, 2011 modified version, improvement to score 0 (clear skin); pasi, psoriasis area and severity index • at week 12, the spearman correlation coefficient between iga and dermatology life quality index responses was 0.43 for secukinumab 300 mg and 0.45 for secukinumab 150 mg safety • rates of adverse events and serious adverse events were similar across all treatment groups (table 2) table 2. summary of adverse events at week 52 preferred term, n (%) secukinumab 300 mg sc (n = 690) secukinumab 150 mg sc (n = 692) etanercept (n = 323) discontinuation due to adverse event 21 (3.0) 25 (3.6) 12 (3.7) any serious adverse event 48 (7.0) 48 (6.9) 20 (6.2) any adverse event 575 (83.3) 562 (81.2) 253 (78.3) most common adverse events (> 5%) nasopharyngitis 172 (24.9) 164 (23.7) 86 (26.6) headache 79 (11.4) 65 (9.4) 40 (12.4) diarrhea 54 (7.8) 45 (6.5) 22 (6.8) upper respiratory tract infection 53 (7.7) 64 (9.2) 18 (5.6) cough 45 (6.5) 21 (3.0) 12 (3.7) back pain 37 (5.4) 30 (4.3) 26 (8.0) hypertension 35 (5.1) 37 (5.3) 14 (4.3) arthralgia 34 (4.9) 38 (5.5) 23 (7.1) sc, subcutaneous conclusions • secukinumab provides early and sustained skin clearance for patients with moderate-to-severe psoriasis – up to 65% of patients achieved complete or nearcomplete clearance of psoriasis after 1 year of treatment as measured by iga mod 2011 0/1 • the safety profile of secukinumab remained favorable and comparable to that of etanercept • in patients receiving secukinumab, response rates were similar between iga mod 2011 0 and pasi 100 and between iga mod 2011 0/1 and pasi 90 groups – at week 52, with secukinumab 300 mg, iga mod 2011 0 was achieved by 37.8% of patients and pasi 100 was achieved by 40.8% of patients; similarly, iga 0/1 was achieved by 64.9% of patients and pasi 90 was achieved by 68.1% of patients8 results secukinumab provides complete or almost-complete psoriasis clearance in moderate-to-severe plaque psoriasis: pooled analysis of 4 phase 3 trials a blauvelt1, a armstrong2, p rich3, r kisa4, a guana4, x meng4, k callis duffin5 1oregon medical research center, portland, or, usa; 2university of southern california keck school of medicine, los angeles, ca, usa; 3oregon dermatology and research center, portland, or, usa; 4novartis pharmaceuticals corporation, east hanover, nj, usa; 5university of utah, salt lake city, ut, usa download document at the following url: http://novartis.medicalcongressposters.com/default.aspx?doc=a90dd and via text message (sms) text: qa90dd to: 8nova (86682) us only +18324604729 north, central and south americas; caribbean; china +447860024038 uk, europe & russia +46737494608 sweden, europe scan to download a reprint of this poster references 1. langley rg et al, for the erasure and fixture study groups. n engl j med. 2014;371:326-338. 2. mease pj et al, for the future 1 study group. n engl j med. 2015;373:1329-1339. 3. bissonnette r et al. br j dermatol. 2017 jun 5. [epub ahead of print]. 4. viswanathan hn et al. j dermatolog treat. 2015;26:235-239. 5. langley rg et al. j dermatolog treat. 2015;26:23-31. 6. blauvelt a et al, for the feature study group. br j dermatol. 2015;172:484-493. 7. paul c et al, for the juncture study group. j eur acad dermatol venereol. 2015;29:1082-1090. 8. kircik l et al. dermatol ther (heidelb). 2016;6:627-638. disclosures a blauvelt: scientific adviser and clinical study investigator for abbvie, amgen, boehringer-ingelheim, celgene, dermira, genentech, glaxosmithkline, janssen, lilly, merck, novartis, pfizer, regeneron, sandoz, sanofi genzyme, sun pharmaceutical industries, ucb, valeant; paid speaker for lilly, regeneron, sanofi genzyme. a armstrong: investigator and/or adviser to abbvie, amgen, celgene, janssen, merck, lilly, novartis, pfizer. p rich: consultant, investigator, speaker, and/or adviser for, and/or received travel and/or research grants from lilly, novartis, boehringer-ingelheim, janssen, pfizer, merck, amgen, abbvie. r kisa, a guana, x meng: employees of novartis pharmaceuticals corporation. k callis duffin: grant/research support from amgen, lilly, janssen, stiefel, abbvie, bms, celgene, novartis; consultant for amgen, lilly, janssen, stiefel, abbvie, bms, celgene, pfizer, novartis. acknowledgements the authors thank the patients and their families and all investigators and their staff for participation in the study. oxford pharmagenesis, inc., newtown, pa, usa, provided assistance with layout and printing the poster; this support was funded by novartis pharmaceuticals corporation, east hanover, nj. the authors had full control of the contents of this poster. this research was funded by novartis pharma ag, basel, switzerland. originally presented at: 36th annual fall clinical dermatology conference, las vegas, nv, usa; october 12–15, 2017. poster presented at: 13th annual winter clinical dermatology conference, maui, hi, usa; january 12–17, 2018. skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 178 brief article eccrine poromatosis following lymphoma treatment: a case report and literature review suzanne alkul, md1, rachel graubard, bs1, carina wasko, md1 1department of dermatology, baylor college of medicine, houston, tx eccrine poromas, benign adnexal neoplasms of the eccrine sweat ducts, arise gradually as isolated lesions on the palms or soles, where sweat glands are highly concentrated. tumors manifest clinically as tender or asymptomatic, erythematous papules or nodules.1 on histological examination, eccrine poromas are characterized by a well-circumscribed, uniform proliferation of glycogen-rich cuboidal cells with abundant eosinophilic cytoplasm and scattered ducts, extending into the dermis.2 rarely, patients present with a sudden eruption of multiple poromas, a phenomenon known as poromatosis. while the pathogenesis is unclear, cases of eccrine poromatosis are typically reported in immunocompromised patients who have received chemotherapy, radiation, or chronic immunosuppressive therapy following stem cell transplantation.3-19 occurrence of lesions has also been attributed to genetic predisposition, radiation-induced damage, or human papillomavirus, all contributing to impaired immunity.4-8 crops of lesions may appear shortly after the onset of therapy or years after completion. herein, we present a case of eccrine poromatosis in a patient with a previous history of t-cell lymphoma, initially diagnosed 18 years prior to presentation and eventually achieving sustained remission after 4 years with a combination of chemotherapy, radiation, and salvage stem cell transplant. a 79-year-old hispanic man presented with a several month history of 5 pruritic, domeshaped, erythematous papules on the left abstract eccrine poromas are benign tumors that arise from the eccrine sweat ducts, commonly presenting as solitary lesions. eccrine poromatosis, the sudden eruption of multiple eccrine poromas, is a rare phenomenon that generally occurs in immunosuppressed patients at any time after receiving treatment for malignancy. we report a case of eccrine poromatosis in a 79-year-old male patient with a previous history of recurrent t-cell lymphoma. over the course of his disease, he was treated with polychemotherapy, radiation, and a definitive bone marrow transplant. the patient presented to the dermatology clinic 18 years after his initial diagnosis with a new onset of pruritic papules on the neck and chest. histologic evaluation revealed all lesions to be eccrine poromas. this is the longest reported time interval between initial diagnosis of a primary malignancy and development of eccrine poromatosis. there is no evidence at this time to suggest that appearance of such lesions is indicative of cancer recurrence; therefore, there is no indication for further oncologic evaluation. introduction case presentation skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 179 figure 1. (a) left neck with one erythematous papule. (b) upper mid chest and right chest with 4 erythematous papules. (c) broad anastomosing bands of monotonous epithelial cells with a broad connection to the epidermis. (h&e, 20x). (d) basophilic epithelial nuclei and sweat ducts within the tumor. (h&e, 200x) neck and right chest in a seatbelt distribution (insert figure 1). his previous medical history is significant for stage 1a t-cell lymphoma, diagnosed 18 years prior to presentation, for which he received 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (chop). he relapsed for the first time 3 years later and was treated with radiation therapy, achieving complete remission. after a second recurrence 1 year later, he received 3 additional cycles of etoposide, methylprednisolone, cytarabine, and cisplatin (eshap). this was followed by a a. b. c. d. skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 180 sibling allogeneic stem cell transplant, for which he was conditioned with etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (epoch), and fludarabine. post-transplant course was complicated by minor graft-versus-host disease (gvhd) of the skin. he has been in complete remission and has not required any immunosuppressive medications since then. all 5 lesions were treated with shave removal followed by electrodessication. histology revealed thick anastomosing bands of monotonous epithelial cells, which had a broad connection to the epidermis and interspersed eccrine ducts (figure 1). no further treatment was pursued. the patient has had no recurrence of the treated lesions nor development of any new poromas. the simultaneous eruption of multiple eccrine poromas is an exceedingly rare phenomenon, and the exact etiology remains poorly understood. while the immunosuppressive effects of infection, pregnancy, and certain medications have been cited as potential catalysts for sudden development of multiple tumors, the first two reported patient cases of poromatosis did not include a previous history of immunosuppression or other predisposing risk factors.7,18,20-23 other cases have been attributed to systemic lupus erythematosus, requiring chronic immunosuppressive therapy, or predisposing genetic conditions, such as hidrotic ectodermal dysplasia.24,25 interestingly, in a canine patient, multiple eccrine poromas were found following amputation of a chronically inflamed paw, previously treated with laser surgery to correct a congenital anomaly.26 because poromas are benign, adnexal tumors that arise from the sweat gland duct, they may originate from either eccrine or apocrine lineages. while eccrine poromas comprise the vast majority of reported cases, apocrine poromas occur with less frequency. clinically, both lesions present similarly as singular, flesh-colored papules on the acral surfaces; therefore, lesions must be differentiated histologically.2 unlike eccrine poromatosis, cases of multiple apocrine poromas have not been associated with a previous history of immunosuppression.27,28 overall, reports of eccrine poromatosis have demonstrated a strong association with lymphoproliferative malignancies treated with immunosuppressive therapies; however, their clinical course is unpredictable, as lesions may appear at any time.3-19 presently, the longest reported period of time between onset of malignancy and emergence of eccrine poromatosis is 16 years.8 this patient presented 18 years after his original diagnosis with t cell lymphoma. to our knowledge, this is the longest interval between onset of a primary malignancy and emergence of eccrine poromatosis and the first case associated with non-cutaneous t cell lymphoma. out of 21 reported cases of eccrine poromatosis associated with malignancy, 7 patients were primarily diagnosed with acute myeloid leukemia, and 10 patients were diagnosed with a particular subtype of nonhodgkin lymphoma (table 1). only one previously documented case has been associated with a neoplasm of t-cell origin.3 in the first case of malignancy-associated eccrine poromatosis, kurokawa et al. (2001) described a 72 year-old male with mycosis fungoides, the most common form of cutaneous t-cell lymphoma. the patient was treated with multiple courses of electron beam radiation therapy for recurrence of skin lesions, and 6 years after his initial diagnosis, the first eccrine poroma was excised and diagnosed. rather than a single eruption of multiple lesions, the patient discussion skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 181 table 1. reported cases of eccrine poromatosis associated with malignancy reference patient age & gender associated malignancy treatment received interval between diagnosis and presentation comments kurokawa et al., 2001; myazaki, japan3 72 male mycosis fungoides electron beam radiation 6 years mahlberg et al., 2006; philadelphia, pa4 42 male acute lymphocytic leukemia (all) chemotherapy; total body radiation; allogeneic bone marrow transplant 2 years transplant complicated by graft-versus-host disease (gvhd) navi et al., 2008; davis, ca,5 64 male non-hodgkin lymphoma chemotherapy unknown sherman et al., 2010; oxford, united kingdom6 32 male acute myeloid leukemia (aml) chemotherapy; total body radiation; allogeneic bone marrow transplant (2) 6 years both transplants complicated by gvhd diamantis et al., 2011; austin, tx7 53 male mantle cell lymphoma allogeneic stem cell transplant 5 years transplant complicated by gvhd; lesions positive for hpv fujii et al., 2012; okayama, japan8 66 female chronic lymphocytic leukemia (cll); b-cell follicular lymphoma chemotherapy; radiation 16 years fujii et al., 2012; okayama, japan8 62 male malignant fibrous histiocytoma chemotherapy; radiation 10 years fujii et al., 2012; okayama, japan8 59 male b-cell lymphoma chemotherapy 6 months fujii et al., 2012; okayama, japan8 72 male b-cell lymphoma chemotherapy 10 years nguyen et al., 2012; san diego, ca9 25 male aml chemotherapy; autologous bone marrow transplant 11 years skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 182 miura & yamamoto 2013; fukushima, japan10 72 female nasolacrimal duct adenocarcinoma radiation rapid onset after radiation therapy garshick et al., 2014; new york, ny11 46 male aml chemotherapy; autologous stem cell transplant months deckelbaum et al., 2014; long beach, ca12 73 male testicular lymphoma chemotherapy; radiation 13 years mayo et al., 2015; birmingham, al13 43 male mantle cell lymphoma chemotherapy; autologous stem cell transplant 4 years takahashi et al., 2015; hokkaido, japan14 63 female aml chemotherapy; autologous stem cell transplant 15 years aung et al., 2017; houston, tx15 45 male aml chemotherapy; allogeneic stem cell transplant 3 months transplant complicated by cmv infection; lesions positive for hpv and mcpyv lim et al., 2018; london, united kingdom16 63 female breast cancer chemotherapy; radiation 6 years valdebran et al., 2018 irvine, ca17 32 female acute promyelocytic leukemia (apml) chemotherapy; bone marrow transplant 7 years nguyen et al., 2019 los angeles, ca18 58 male large b-cell lymphoma chemotherapy; radiation 10 years nguyen et al., 2019 los angeles, ca18 72 male 1) mantle cell lymphoma 2) prostate cancer 1) chemotherapy; stem cell transplant 2) radiation 10 years marsh et al, 2020 columbus, o19 47 female aml chemotherapy; total body radiation; allogeneic stem cell transplant 3 years transplant complicated by gvhd skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 183 continued to develop 14 eccrine poromas in several different areas of chronically irradiated skin over the course of 12 years.3 primary malignancies associated with poromatosis were reportedly treated with various combinations of therapy, involving chemotherapy, radiotherapy, or stem cell transplantation. the correlation of poromatosis following the use of chemotherapeutic agents suggests that the accumulation of cytotoxic metabolites potentially alters the structural integrity of the sweat glands, facilitating synchronous occurrence of several eccrine poromas.8 after cell damage or trauma occurs, cellular repair is initiated through remodeling and regeneration, creating increased potential for neoplastic transformation. such changes occur gradually over time, leading to the delayed presentation of lesions.19 similarly, clusters of eccrine poromas have appeared in areas of irradiated skin or within preexisting chronic radiation dermatitis, suggesting x-ray damage may also contribute to tumor development.3,20 in the initial treatment of the primary malignancies, only 3 previous cases of malignancy-associated poromatosis have involved the use of all 3 therapeutic modalities mentioned above.7,15,19 in each case, the post-transplantation course was complicated by either graft-versus-host disease or cytomegalovirus infection.7,15,19 this finding suggests a possible role of the immune response creating inflammatory damage to the sweat ducts, leading to emergence of eccrine poromatosis. our patient presents a unique clinical course, as he was treated in a stepwise fashion. he initially received polychemotherapy, followed by radiation after his first relapse, and bone marrow transplant was used as salvage therapy after a second relapse. while multiple etiologies have been suggested, overall, immunosuppressed patients appear to be particularly vulnerable to formation of multiple eccrine poromas. at this time, there is no evidence in the literature to suggest poromatosis is a harbinger of malignancy recurrence or relapse. however, patients with a history of malignancy should continue to be cognizant of signs and symptoms of recurrence as directed by their oncologist. conflict of interest disclosures: none funding: none corresponding author: suzanne alkul, md department of dermatology baylor college of medicine 1977 butler blvd houston, tx 77030 phone: 713-798-6131 fax: 713-798-6923 email: alkul@bcm.edu references: 1. wankhade v, singh r, sadhwani v, kodate p. eccrine poroma. indian dermatol online j. 2015;6(4):95-98. 2. sawaya jl, khachemoune a. poroma: a review of eccrine, apocrine, and malignant forms. int j dermatol. 2014;53(9):1053-1061. 3. kurokawa m, amano m, miyaguni h, et al. eccrine poromas in a patient with mycosis fungoides treated with electron beam therapy. brit j dermatol. 2001;145(5):830-833. 4. mahlberg mj, mcginnis ks, draft ks, fakharzadeh ss. multiple eccrine poromas in the setting of total body irradiation and immunosuppression. j am acad dermatol. 2006;55(2):s46-s49. 5. navi, d., fung, m., & lynch, p. j. poromatosis: the occurrence of multiple eccrine poromas. dermatol online j. 2008;14(1). 6. sherman v, reed j, hollywood k, et al. poromas and porokeratosis in a patient treated for solidorgan and haematological malignancies. clin exp dermatol. 2009;35:e130-e132. 7. diamantis ml, richmond hm, rady pl, et al. detection of human papillomavirus in multiple eccrine poromas in a patient with chronic graftvs-host disease and immunosuppression. arch dermatol. 2010;147(1):120-122. skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 184 8. fujii k, aochi s, takeshima c, et al. eccrine poromatosis associated with polychemotherapy. acta derm venereol. 2012;92(6):687-690. 9. nguyen bt, lortscher, dn, & lee ra. multiple poromas in a bone marrow transplant recipient: a case report. dermatol online j. 2012;18(7). 10. miura t, yamamoto t. eruptive poromatosis following radiotherapy. am j dermatopathol. 2013;35:615-617. 11. garshick m, defilippis em, harp j, et al. eccrine poromatosis in a patient with acute myeloid leukemia following chemotherapy. dermatol online j. 2014;20(11). 12. deckelbaum s, touloei k, shitabata pk, sire dj, horowitz d. eccrine poromatosis: case report and review of the literature. int j dermatol. 2013;53(5):543-548. 13. mayo tt, kole l, elewski b. eccrine poromatosis: case report, review of the literature, and treatment. skin appendage disord. 2015;1(2):95-98. 14. takahashi c, nishi k, minami-hori m, et al. multiple poromas following combination chemotherapy and autologous peripheral blood stem cell transplantation. j dermatol. 2015;42:430-432. 15. aung pp, rady pl, nagarajan p, et al. detection of merkel cell polyoma virus and beta human papillomavirus in multiple eccrine poromas in a patient with acute leukemia treated with stem cell transplant. am j dermatopathol. 2017;39(6):489-491. 16. lim tm, weir j, fearfield l. eruptive poromatosis in a patient with breast cancer. j cutan pathol. 2018;45:708-710. 17. valdebran ma, hong c, cha j. multiple eruptive eccrine poromas associated with chemotherapy and autologous bone marrow transplantation. indian dermatol online j. 2018;9:259-261. 18. nguyen k, kim, g, & chiu, m. eccrine poromatosis following chemotherapy and radiation therapy. dermatol online j. 2019; 25(11). 19. marsh rl, kaffenberger b, pootrakul l, et al. multiple plantar poromas in a stem cell transplant patient. cureus. 2020;12(6): e8773. 20. ullah k, pichler e, fritsch p. multiple eccrine poromas arising in chronic radiation dermatitis. acta derm venereol. 1989;69(1):70. 21. north jp, lo j, landers m. poromatosis in pregnancy: a case of 8 eruptive poromas in the third trimester. cutis. 2012;89(2): 81-83. 22. goldner r. eccrine poromatosis. arch dermatol. 1970;101(5):606-608. 23. ogino a. linear eccrine poroma. arch dermatol. 1976; 112(6):841-844. 24. yoshii y, matsuo s, nishizawa a, satoh t. multiple eccrine poromas in a patient with systemic lupus erythematosus. eur j dermatol. 2018 dec 1;28(6):837. 25. wilkinson rd, schopflocher p, rozenfeld m. hidrotic ectodermal dysplasia with diffuse eccrine poromatosis. arch dermatol. 1977;113(4):472–476. 26. whitley db, mansell jekl. multiple eccrine poromas in the paw of a dog. veterinary dermatology. 2011;23(2):167-e34. 27. nishioka m, kunisada m, fujiwara n, oka m, funasaka y, nishigori c. multiple apocrine poromas: a new case report. j cutan pathol. 2015 nov;42(11):894-896. 28. hashizume s, ansai s, matsuoka y, omi t, kawana s. case of multiple apocrine poroma in a patient without receiving radiation or chemotherapy. j dermatol. 2014 feb;41(2):174175. skin january 2018 volume 2 issue 1 copyright 2017 the national society for cutaneous medicine 30 in-depth reviews status report on the safety of topical dapsone therapy for dermatologic disease megan a. jones do a , richard r. winkelmann do b , james q. del rosso do c,d,e a department of dermatology, lehigh valley health network b department of dermatology, ohiohealth hospital c touro university, henderson, nv d jdr dermatology research, las vegas, nv e dermatology and cutaneous surgery, thomas dermatology, las vegas, nv dapsone is a synthetic sulfone antibiotic that was synthesized in 1908 and initially used for the treatment of leprosy (figure 1). 1-3 at that time, clinicians incidentally noticed that administration of oral dapsone led to a marked improvement of acne, including in patients with severe inflammatory disease. 2,4 subsequently, dapsone was widely adopted to treat severe cases of acne prior to the development of oral isotretinoin. 5 today, oral dapsone is used as a primary or adjuvant therapy in many rare and refractory dermatological conditions (table 1). 2,3,6 figure 1. chemical structure of dapsone, a sulfone. the efficacy of dapsone in treating dermatologic disease is largely attributed to its anti-inflammatory and anti-microbial properties. dapsone’s anti-inflammatory action is secondary to monoacetyl dapsone and dapsone hydroxylamine (dds-noh), two metabolites activated by enzymatic reactions occurring within cutaneous polymorphonuclear leukocytes. 2 several in vitro studies have demonstrated that abstract systemic dapsone therapy has historically been used to treat leprosy, inflammatory dermatoses, and severe cases of acne vulgaris. this article reviews the pharmacokinetics, short and long-term safety, drug-drug interactions, gender, and age effects of topical dapsone 5% and 7.5% gel formulations. in 20 human studies and 7 case reports, 39 of 6,384 total patients (<1%) experienced adverse effects that were considered more than mild or resulted in discontinuation of topical dapsone. the literature supports topical dapsone 5% and 7.5% gels as safe and effective medications for the treatment of dermatologic disease. introduction sulfone (dapsone) skin january 2018 volume 2 issue 1 copyright 2017 the national society for cutaneous medicine 31 dapsone decreases inflammation by scavenging reactive oxygen species, inhibiting neutrophil myeloperoxidase, inhibiting eosinophil peroxidase, and suppressing hypochlorous acid production. 2,7-10 the anti-microbial properties of dapsone are due to competitive inhibition of bacterial para-aminobenzoic acid (paba) which decreases the production of dihydrofolic acid. 11 studies of acne vulgaris have also shown that dapsone has antibacterial activity against propionibacterium acnes. 2 dapsone and its metabolites effectively treat many dermatologic diseases, however, systemic accumulation may cause adverse hematologic and neurologic events. 2 high systemic exposure can lead to dosedependent reactions including methemoglobinemia, hemolysis, and agranulocytosis among others (table 2). 2 topical 5% and 7.5% semi solid-gel formulations of dapsone have since been developed with markedly reduced systemic accumulation, minimizing many of the concerns regarding systemic toxicity. 12-14 however, long term safety data for topical dapsone is limited. 8 the purpose of this review is to comprehensively outline the safety evidence from relevant studies evaluating dapsone 5% and 7.5% gel as topical therapy for dermatologic disease. table 1. reported indications for dapsone (oral and topical) chronic skin conditions sulfone sensitive dermatoses other acropustulosis infantilis bullous pemphigoid leprosy (multibacillary and paucibacillary) dermatitis herpetiformis chronic idiopathic urticaria rheumatoid arthritis erythema elevatum et diutinum cutaneous lupus erythematosus antimalarial iga pemphigus eosinophilic folliculitis eosinophilic fasciitis linear iga dermatosis leukocytoclastic vasculitis immune thrombocytopenia prurigo pigmentosa lichen ruber pemphigoides asthma bronchiale subcorneal pustular dermatosis loxoscelism glioblastoma *acne vulgaris mucous membrane pemphigoid seizures *papulopustular rosacea pemphigus vulgaris prophylaxis in aids **granuloma faciale pyoderma gangrenosum **lupus erythematosus recurrent neutrophilic dermatosis of dorsal hands **hidradenitis relapsing polychondritis **dermatitis herpetiformis sweets syndrome **venous stasis ulcer inverse and pustular psoriasis **erosive pustular dermatosis of the scalp **erythema elevatum diutinum *topical dapsone gel 5% indication on u.s. market **off-label reported use of topical dapsone 5% gel, noted in literature to respond skin january 2018 volume 2 issue 1 copyright 2017 the national society for cutaneous medicine 32 table 2. adverse effects of oral dapsone hematologic cutaneous gastrointestinal nervous system other methemoglobine mia exfoliative dermatitis anorexia peripheral neuropathy *hypersensitivity syndrome hemolysis erythema multiforme abdominal pain motor function loss albuminuria agranulocytosis urticaria nausea insomnia erythema nodosum vomiting psychosis morbilliform lft abnormalities electrolyte abnormalities scarlatiniform exanthema prehepatic jaundice atrioventricular block toxic epidermal necrolysis cholestatic hepatitis photosensitivity rash in aids patients *fever, rash, lymphadenopathy, hepatic dysfunction a pubmed search for any randomized clinical trials (rct) related to topical dapsone, dapsone gel, or the trade name, aczone ® [allergan, dublin, ireland] was performed. studies that were not randomized or placebo controlled were included only if performed on a large number of patients. considerable effort was made to find all available articles from the united states and other countries. the primary objective of the review was to include all studies that reported adverse events, side effects, toxicity, and laboratory parameter changes caused by topical dapsone 5% and 7.5% gel. overall, 20 clinical studies and 7 case reports met the criterion for this review that analyzed the pharmacokinetics, short-term safety, gender effects, age effects, long-term safety, drug-drug interactions, and safety in high risk patients utilizing topical dapsone 5% or 7.5% gel (table 3). pharmacokinetic studies the systemic exposure of topical dapsone was evaluated by testing the difference in plasma concentrations of patients using topical vs. oral dapsone[16]. thiboutot et al studied 18 patients who received 14 days of topical dapsone 5% gel twice daily, followed with a 14-day washout period. patients were then given a one-time 100 mg dose of oral methods results skin january 2018 volume 2 issue 1 copyright 2017 the national society for cutaneous medicine 33 table 3. adverse effects of topical dapsone reported in clinical trials study year n study details outcomes/adverse events human studies application site ae’s non-application site ae’s lab abnormalities/ systemic exposure withdrawal from study secondary to treatment ae thiboutot, et al 2007 18 evaluate systemic concentrations of oral and topical dapsone not evaluated. not evaluated. steady state exposure of topical versus oral dapsone was 126 fold lower. no hematologic ae’s. 0 thiboutot, et al 2007 17 drug interaction study: dapsone gel and oral tmp/smx not evaluated. not evaluated. plasma concentration of dapsone was increased when combined with tmp/sxt. no hematologic ae’s. 3 (17.65%) lucky, et al 2007 486 long term safety of dapsone mild to moderate application site ae’s: dryness, rash, sunburn, burning, erythema, pruritus, acne aggravated, peeling, rash nonspecific, contact dermatitis, irritation, seborrheic dermatitis, and caustic injury(8.2%) non-application site ae’s: headache (20%), nasopharyngitis (15%), pharyngitis (9%), sinusitis (6%), upper respiratory tract infection (5%), and dysmenorrhea (6%), nausea secondary to drug odor(0.2%) mean plasma concentration of dapsone remained low. no hematologic ae’s. 11 (2.26%) draelos, et al 2007 3010 short term efficacy and safety of topical dapsone mild to moderate application site ae’s: oiliness, erythema, dryness, and peeling(38%) non-application site ae’s: nasopharyngitis, headache, upper respiratory tract infection, and pharyngitis(1%) lab abnormalities related to treatment (0.25%): elevated creatinine kinase no other hematologic ae’s. 2 (0.14%) raimer, et al *subanalysis 2008 1306 assess safety of topical dapsone in adolescents (12-15 yo) mild application site ae’s: dryness, erythema(20.2%) 1 contact dermatitis non-application site ae’s: nasopharyngitis(7.7%), headache (4.7%) 1 increased blood creatinine phosphokinase level. no other hematologic ae’s. 2 (0.26%) skin january 2018 volume 2 issue 1 copyright 2017 the national society for cutaneous medicine 34 study year n study details outcomes/adverse events application site ae’s non-application site ae’s lab abnormalities/ systemic exposure withdrawal from study secondary to treatment ae tanghetti, et al *subanalysis 2012 2898 assess efficacy and tolerability of dapsone in female versus male patients mild application site ae’s: erythema(~15%), oiliness (~20%), dryness (~3%), peeling (~1%) none reported no hematologic ae’s. not reported del rosso, et al *subanalysis 2015 781 assess efficacy and tolerability of dapsone in adult versus adolescent females mild application site ae’s: erythema(14%), dryness(3%), oiliness(15%), and peeling(2%) none reported no hematologic ae’s. not reported piette, et al 2008 63 safety of topical dapsone in g6pd deficient patients mild to moderate application site ae’s: burning, dryness, pruritus, contact dermatitis and aggravated acne (12.7%) none reported 3 patients(4.7%) experienced a lab abnormality: elevated bilirubin, low haptoglobin, low white blood cell count no significant change in hemoglobin between dapsone and control. 0 faghihi, et al 2014 58 assess efficacy of dapsone 5% gel combined with oral isotretinoin mild application site ae’s: burning (24%), erythema (14%) and dryness (10%), exfoliation(3.4%), pruritus(3.4%), photosensitivity(3.4%) (62% total 18/29) 1 contact conjunctivitis. not evaluated. no hematologic ae’s. 0 tanghetti, et al 2011 171 assess safety and efficacy of dapsone when combined with tazarotene mild application site ae’s: dryness(2.3%), erythema(2.3%) not evaluated. no hematologic ae’s. 0 skin january 2018 volume 2 issue 1 copyright 2017 the national society for cutaneous medicine 35 study year n study details outcomes/adverse events application site ae’s non-application site ae’s lab abnormalities/ systemic exposure withdrawal from study secondary to treatment ae fleischer, et al 2010 292 assess safety and efficacy of dapsone when combined with adapalene, bpo, or moisturizer mild application site ae’s: erythema (most common), oiliness, dryness, peeling, burning, pruritus, rash (average 10.67%) drug interaction (7 patients in dapsone/bpo group only) non-application site ae’s: nasopharyngitis, upper respiratory tract infection, headache, pharyngitis, nasal congestion, cough, sinusitis, abrasion, ear pain, and fungal vaginosis(average 35%) plasma dapsone and n-acetyl dapsone levels remained low no hematologic ae’s. 9 (3%) grove, et al 2013 140, (25 topical dapsone) assess tolerability and irritation potential of duac gel compared with dapsone(aczone) mild application site ae’s: erythema, sebum production, perceived burning, stinging, and dryness. *based on scores not percentages or numbers of patients non-application site ae’s: headache occurred in all groups(>11%), nausea in dapsone group(8%) no hematologic ae’s. 0 lynde, et al 2014 101 assess efficacy, tolerability, and safety of topical dapsone in adult women with sensitive skin mild application site ae’s: skin irritation (2%) not evaluated. no hematologic ae’s. 2 (2%) faghihi, et al 2015 56 efficacy of dapsone gel + oral doxycycline compared to metronidazole gel+ oral doxycycline in treating papulopustular rosacea mild application site ae’s: dryness, burning, pruritus, scaling, photosensitivity and erythema(average 27.38%) not evaluated. no hematologic ae’s. 2 (7.14%) stein gold, et al 2016 948 assess efficacy, safety, and tolerability of once daily dapsone gel, 7.5% mild-moderate application site ae’s: erythema(0.6%), exfoliation (0.6%), pain (0.2%) non-application site ae’s: nasopharyngitis (1.9%), upper respiratory tract infection (1.4%), headache (1.3%), influenza (1.1%), oropharyngeal pain(1.0%) no hematologic ae’s. 4 (0.4%) skin january 2018 volume 2 issue 1 copyright 2017 the national society for cutaneous medicine 36 study year n study details outcomes/adverse events application site ae’s eichenfield, et al 2016 1026 assess efficacy, safety, and tolerability of once daily dapsone gel, 7.5% mild-moderate application site ae’s: dryness(1.5%), pain (0.6%), pruritus (1.0%) non-application site ae’s: nasopharyngitis (1.8%), upper respiratory tract infection (1.5%), headache (1.8%), nasal congestion (1.0%) no hematologic ae’s. 2 (0.2%) thiboutot, et al *subanalysis 2016 2161 assess efficacy and safety of once-daily topical dapsone gel, 7.5% mild-moderate application site ae’s: dryness(1.2%), pruritus(1.1%), pain(0.5%) non-application site ae’s: headache(1.6%), nasopharyngitis(1.9%), upper respiratory tract infection(1.5%) no hematologic ae’s. 3 (0.15%) draelos, et al *subanalysis 2017 2161 assess relationship of age, sex, and race to treatment response of once daily dapsone gel, 7.5% mild-moderate application site ae’s: dryness, erythema, pruritus, pain non-application site ae’s: upper respiratory tract infection, headache, nasopharyngitis, nasal congestion, oropharyngeal pain no hematologic ae’s. not reported. jarratt, et al 2016 72 evaluate pharmacokinetics, safety, tolerability of once-daily dapsone gel, 7.5% and twice daily dapsone gel, 5% mildmoderate application site ae’s: dryness, scaling, erythema, pruritus non-application site ae’s: cough, headache, pharyngitis, upper respiratory tract infection, dysmenorrhea, oropharyngeal pain systemic exposure of once daily dapsone gel 7.5% was 25-40% lower than twice daily dapsone gel 5% no hematologic ae’s, no clinically significant changes in methemoglobin levels, hematology, or blood chemistry. 0 brown, pc allergan 2016 33 evaluate for phototoxicity when using dapsone gel 7.5% no application site or phototoxicity ae’s reported. no non-application site ae’s reported. no hematologic ae’s. 0 skin january 2018 volume 2 issue 1 copyright 2017 the national society for cutaneous medicine 37 dapsone. the mean plasma concentration in patients using topical dapsone was 19.4 ng/ml vs. 1,375 ng/ml in those taking dapsone orally. the steady-state concentration of topical dapsone was 126fold lower than that observed following a one-time dose of 100 mg oral dapsone. no hematologic adverse events were reported. 16 in 2007, thiboutot et al studied the effects of trimethoprim-sulfamethoxazole (tmp-smx) (160/800mg) on dapsone metabolism and its potential for increasing the risk of hemolytic anemia. 16 seventeen non-g6pd deficient patients aged 17-50 years were given tmpsmx monotherapy for 7 days followed by a 7-day washout period. topical dapsone was then administered twice daily for 21 days. topical dapsone and tmp-smx were subsequently co-administered without a washout period for 7 days. serum concentrations of dapsone were increased when applied topically in combination with oral tmp-smx (222-320 ng-h/ml). increased serum levels of dapsone metabolites, monoacetyl dapsone and dapsone hydroxylamine were reported as well (73-88 ng-h/ml and 18-44 ng-h/ml, respectively). no hematologic adverse events were reported. 16 clinical studies two studies conducted by draelos et al evaluated the efficacy and safety of topical dapsone in treating acne vulgaris. 17 three thousand and ten patients with moderate acne vulgaris were randomized to either 5% dapsone gel or vehicle gel twice daily for 12 weeks. adverse events were reported at similar rates in the treatment (58.2%) and vehicle control groups (58.6%). application site adverse reactions occurred at similar rates in both treatment and vehicle control groups (38% vs. 37.8%, respectively) of which only 1% were considered treatmentrelated. two patients withdrew from the dapsone treatment group due to pruritus, burning, dryness, erythema, stinging, and/or peeling. twenty of the patients (1.3%) treated with dapsone gel experienced laboratory abnormalities (most commonly elevated creatinine kinase), of which 4 were considered related to treatment. no significant changes in hemoglobin or other laboratory parameters were reported in any patients with or without g6pd deficiency. 17 subanalyses of the original studies described above have further evaluated the safety and efficacy of dapsone 5% gel in specific populations. raimer et al analyzed safety data in adolescents 12-15 years of age (n=1306) and found no previously unrecognized adverse effects or safety concerns. 18 tanghetti et al analyzed differences in the efficacy and tolerability of dapsone 5% gel (n=2,898) between men and women in treating acne vulgaris. 19 the adverse effects reported did not differ significantly based on gender or treatment arm (p>0.05 at 12 weeks). additionally, del rosso compared the efficacy and safety of topical dapsone therapy in adult women (>18 years of age) and adolescent women (12 to 17 years of age) with acne vulgaris (n=781). 20 this sub-analysis demonstrated that adolescent and adult female patients using dapsone 5% gel reported fewer application site adverse events after 12 weeks of use than at baseline. an open label, non-comparative study to evaluate the long-term safety of topical dapsone 5% gel in treating mild to moderate acne vulgaris was performed by lucky et al. 21 four hundred and eighty-six patients were given topical dapsone 5% gel twice daily for 12 months. the study reported 9.5% (46/486) of patients experienced an adverse event related to treatment; 8.2% skin january 2018 volume 2 issue 1 copyright 2017 the national society for cutaneous medicine 38 (40/486) of patients experienced mild to moderate application site adverse events which led to withdrawal from the study for ten patients. non-application site adverse events were experienced on average in 10% of patients and led to withdrawal in only one patient who experienced nausea, dizziness, and weakness secondary to drug odor. average plasma dapsone levels were 11.0 ng/ml after one month and 7.5 ng/ml at month twelve. there were no clinically significant changes from baseline hematology or serum chemistries. five patients were g6pd deficient and their hemoglobin levels remained stable throughout the course of therapy. 21 a phase one, randomized, parallel-group, active-controlled, multiple-dose study was conducted by jarratt et al. to compare the safety, tolerability, and pharmacokinetic profile of topical dapsone 7.5% gel to that of topical dapsone 5% gel. blood samples were collected from 72 patients 16-35 years of age with moderate acne throughout the study to evaluate the plasma concentration of dapsone and its metabolites. one treatment related adverse event, mild pruritus, occurred in a patient receiving dapsone 5% gel. mean combined dermal tolerability scores for dryness, scaling, and erythema were low for both treatment groups. no adverse clinical or laboratory adverse events led to study discontinuation in any patient. 35 two similarly designed phase iii randomized, double-blind, vehicle controlled, multi-center studies were conducted to evaluate the efficacy and safety of dapsone 7.5% gel for treating acne vulgaris in patients aged 12 years and older. 36,37 patients (n=3977) with moderate acne vulgaris were given either 7.5% dapsone gel or vehicle gel once daily for 12 weeks. adverse events were reported at similar rates in the treatment and vehicle control groups. in the first study, 19.1% and 20.6% of patients in the treatment and vehiclecontrolled groups reported adverse events, respectively. the second study did not demonstrate a significant difference in adverse events in treatment (17.6%) and vehicle-controlled (17.1%) groups. reported adverse events included mild to moderate application site erythema, exfoliation, dryness, pain, and pruritus. five of the six patients who withdrew from the study cited the development of application site acne, dermatitis, pruritic rash, vesicles, swelling, and erythema. one patient withdrew following a diagnosis of acute myeloid leukemia. pooled subanalyses of these phase iii studies showed similar tolerability of topical dapsone 7.5% gel when grouped by age, sex, and race. 38 thiboutot et al sub analyzed the safety and tolerability of topical dapsone 7.5% gel in comparison to vehicle only. 39 treatment-related adverse events were similar between dapsone 7.5% gel groups and vehicle groups, 18.3% and 18.8% respectively. tolerability of topical dapsone 7.5% was comparable to tolerability of vehicle gel. stinging/burning, dryness, scaling, and erythema were most commonly reported (<0.5 mean tolerability scores for topical dapsone, 0=none, 1=mild) and <1% had a significant decrease in dermal tolerability throughout the study. 39 a 2014 phase i study was completed to evaluate for topical dapsone-induced phototoxicity in 33 healthy volunteers 18-65 years of age. topical dapsone gel was applied daily to the skin of patients over four days and no adverse phototoxic effects were reported. 40,41 the therapeutic benefit and safety of topical dapsone in combination with other skin january 2018 volume 2 issue 1 copyright 2017 the national society for cutaneous medicine 39 established acne therapies was studied including topical tazarotene, adapalene, benzoyl peroxide (bp), clindamycin phosphate, as well as oral isotretinoin and tmp/smx (previously described) (total n=717). only 11 patients withdrew from these studies due to dapsone intolerance or mild adverse events. seven patients using topical dapsone with bp described a “temporary tan residue” following concurrent application. for all treatment groups, plasma dapsone and monoacetyl dapsone levels remained low. all application site adverse events were mild in severity and no clinically significant changes in laboratory parameters were reported. 22-26 a study of 63 patients was conducted by piette et al to assess the safety of topical dapsone 5% gel in high-risk patients with g6pd deficiency. 27 fourteen patients were considered severely g6pd deficient, yet no signs or symptoms of hemolytic anemia were detected in this group. eight of 63 patients reported adverse events considered related to the study treatment. laboratory testing detected adverse events in 3 study subjects. a mean reduction of hemoglobin by 0.32 g/dl was noted 2 weeks after initiating therapy, however, these changes were transient. 27 laboratory parameters suggestive of hemolysis (i.e decreased haptoglobin, increased bilirubin, ldh, or reticulocyte counts) did not accompany these findings. lynde evaluated the safety, efficacy, and tolerability of topical dapsone 5% therapy in patients with sensitive skin (n=101). 28 adult women with mild to moderate inflammatory acne applied dapsone 5% gel twice daily. two patients withdrew from the study due to mild skin irritation. of the women experiencing skin irritation, most developed a tolerance over time with repeated use of topical dapsone. no other adverse effects were reported. 28 case reports two case reports of topical dapsone 5% gel induced methemoglobinemia have been reported. 15,29 swartzenruber reported methemoglobinemia in a 19-year-old female being treated with topical dapsone for acne vulgaris. a second report by graff describes methemoglobinemia in a 19-month old girl who inappropriately applied topical dapsone over a large surface area. both patients recovered and remained asymptomatic after methylene blue administration without signs of hemolysis or need for further treatment. 15,29 other case reports describe topical dapsone treating dermatitis herpetiformis, venous stasis ulcers, erosive pustular dermatosis of the scalp, erythema elevatum diutinum, granuloma faciale, lupus erythematosus, and hidradenitis suppurativa. 13,30-34 no adverse events or safety concerns were reported in these studies. the literature evaluated in this review support that topical dapsone [5%, 7.5%] gel can be used to effectively treat cutaneous diseases with limited systemic absorption and without fear of serious side effects. most reported adverse events were mild in severity of skin irritation, and were transient in nature. the largest reviewed study did not report any non-application site adverse events associated with topical dapsone 7.5% gel therapy (n=3977). less than 1% of patients (n=3010) experienced nonapplication site adverse events related to dapsone 5% gel therapy 17,36,37 in another study. thirty-nine of 6,384 (0.61%) total patients from the studies included in this discussion skin january 2018 volume 2 issue 1 copyright 2017 the national society for cutaneous medicine 40 review experienced an adverse event that was considered to be more than mild and/or resulting in discontinuation of therapy. plasma dapsone levels were not affected by long-term topical treatment. safety concerns about using topical dapsone in combination with tmp/smx, isotretinoin, tazarotene, adapalene, bp gel, or clindamycin/bpo were limited and not determined to be clinically relevant; however, application of topical dapsone and topical bp when used in a combination topical regimen are best completed at different times during the day to avoid the potential for a temporary orange discoloration of skin. of the 49 patients studied with g6pd deficiency, none experienced adverse hematologic effects in the short or long-term safety trials. 17,21,35 finally, both cases of methemoglobinemia, although seemingly questionable regarding cause and effect, reinforce the need for clinicians to remain vigilant about signs and symptoms and/or symptoms of adverse events related to increased systemic exposure. clinical trials have demonstrated the effective use of topical dapsone for the treatment of acne vulgaris. additional publications suggest the potential for selected use of topical dapsone for the treatment of other skin conditions such as dermatitis herpetiformis, venous stasis ulcers, erosive pustular dermatosis of the scalp, erythema elevatum diutinum, granuloma faciale, lupus erythematosus, and hidradenitis suppurativa. the present aggregation of studies finds that the rates of adverse events were similar between dapsone gel treated groups and vehicle control groups. local adverse signs and symptoms decreased over the course of therapy. the literature supports topical dapsone as a minimally irritating, welltolerated, and effective medication. further research and pharmacovigilance are warranted to optimally maintain our understanding of the long-term effects of topical dapsone therapy. conflict of interest disclosures: dr. del rosso is a consultant, researcher, and speaker for allergan. funding: none. corresponding author: megan a. jones, do dermatology resident, lehigh valley health network 1259 s. cedar crest blvd. allentown, pa 18103 740-359-8600 meganajones16@gmail.com references: 1. webster gf. is topical dapsone safe in glucose-6-phosphate dehydrogenase-deficient and sulfonamide-allergic patients? j. drugs dermatology. 2010;9:532–6. 2. wozel g, blasum c. dapsone in dermatology and beyond. arch. dermatol. res. 2014;306:103–24. 3. pickert a, raimer s. an evaluation of dapsone gel 5% in the treatment of acne vulgaris. expert opin. pharmacother. [internet]. 2009;10:1515–21. available from: http://www.ncbi.nlm.nih.gov/pubmed/1950 5219 4. barranco vp. dapsone — other indications. int. j. dermatol. 1982;21:513–5. 5. del rosso jq. newer topical therapies for the treatment of acne vulgaris. cutis. 2007;80:400–10. conclusion skin january 2018 volume 2 issue 1 copyright 2017 the national society for cutaneous medicine 41 6. guglielmetti a, conlledo r, bedoya j, ianiszewski f, correa j. inverse psoriasis involving genital skin folds: successful therapy with dapsone. dermatol. ther. (heidelb). 2012;2:1–9. 7. zhu yi, stiller mj. dapsone and sulfones in dermatology: overview and update. j. am. acad. dermatol. 2001;45:420–34. 8. allergan i. aczone gel 5 % [internet]. rx prod. news. 2008 [cited 2016 apr 17]. available from: www.allergan.com 9. kazmierowski ja, ross je, peizner ds, wuepper kd. dermatitis herpetiformis : effects of sulfones and sulfonamides on neutrophil myeloperoxidase-mediated iodination and cytotoxicity. j. clin. immunol. 1984;4:55–64. 10. bozeman pm, learn db, thomas el. inhibition of the human leukocyte enzymes myeloperoxidase and eosinophil peroxidase by dapsone. biochem. pharmacol. 1992;44:553–63. 11. coleman md. dapsone: modes of action, toxicity and possible strategies for increasing patient tolerance. br. j. dermatol. 1993;129:507–13. 12. kircik lh. harnessing the antiinflammatory effects of topical dapsone for management of acne. j. drugs dermatology. 2010;9:667–71. 13. scheinfeld n. aczone, a topical gel formulation of the antibacterial, antiinflammatory dapsone for the treatment of acne. curr. opin. investig. drugs. 2009;10:474– 81. 14. drucker cr. update on topical antibiotics in dermatology. dermatol. ther. 2012;25:6– 11. 15. swartzenruber gs, yanta jh, pizon af. methemoglobinemia as a complication of topical dapsone. n. engl. j. med. [internet]. 2015;372:491–2. available from: http://www.nejm.org/doi/abs/10.1056/nej mc1414788 16. thiboutot dm, willmer j, sharata h, halder r, garrett s. pharmacokinetics of dapsone gel, 5% for the treatment of acne vulgaris. clin. pharmacokinet. 2007;46:697– 712. 17. draelos zd, carter e, maloney jm, elewski b, poulin y, lynde c, et al. two randomized studies demonstrate the efficacy and safety of dapsone gel, 5% for the treatment of acne vulgaris. j. am. acad. dermatol. 2007;56:1–10. 18. raimer s, maloney jm, bourcier m, wilson d, papp k, siegfried e, et al. efficacy and safety of dapsone gel 5% for the treatment of acne vulgaris in adolescents. cutis. 2008;81:171–8. 19. tanghetti e, harper jc, oefelein mg. the efficacy and tolerability of dapsone 5% gel in female vs male patients with facial acne vulgaris: gender as a clinically relevant outcome variable. j. drugs dermatology. 2012;11:1417–21. 20. del rosso jq, kircik l, gallagher cj. comparative efficacy and tolerability of dapsone 5% gel in adult versus adolescent females with acne vulgaris. j. clin. aesthet. dermatol. 2015;8:31–7. 21. lucky aw, maloney m, roberts j, taylor s, jones t, ling m, et al. dapsone 5% gel for the treatment of acne vulgaris: safety and efficacy of long-term (1 year) treatment. j. drugs skin january 2018 volume 2 issue 1 copyright 2017 the national society for cutaneous medicine 42 dermatology. 2007;6:981–7. 22. faghihi g, rakhshanpour m, nilforoushzadeh ma. the efficacy of 5% dapsone gel plus oral isotretinoin versus oral isotretinoin alone in acne vulgaris: a randomized double-blind study. adv. biomed. res. 2014;3:177. 23. faghihi g, khosravani p, nilforoushzadeh ma, hosseini sm, assaf f, zeinali n, et al. dapsone gel in the treatment of papulopustular rosacea: a double-blind randomized clinical trial. j. drugs dermatology. 2015;14:602–6. 24. tanghetti e, dhawan s, green l, ling m, downie j, germain ma, et al. clinical evidence for the role of a topical anti-inflammatory agent in comedonal acne: findings from a randomized study of dapsone gel 5% in combination with tazarotene cream 0.1% in patients with acne vulgaris. j. drugs dermatology. 2011;10:783–92. 25. fleischer ab, shalita a, eichenfield lf, abramovitz w, lucky a, garrett s. dapsone 5% gel in combination with adapalene gel 0.1%, benzoyl peroxide gel 4%, or moisturizer for the treatment of acne vulgaris: a 12-week randomized, double-blind study. j. drugs dermatology. 2010;33–40. 26. grove g, zerweck c, gwazdauskas j. tolerability and irritation potential of four topical acne regimens in healthy subjects. j. drugs dermatology. 2013;12:644–9. 27. piette ww, taylor s, pariser d, jarratt m, sheth p, wilson d. hematologic safety of dapsone gel, 5%, for topical treatment of acne vulgaris. arch. dermatol. [internet]. 2008;144:1564–70. available from: http://archderm.amaassn.org/cgi/content/abstract/144/12/1564 28. lynde cw, andriessen a. cohort study on the treatment with dapsone 5% gel of mild to moderate inflammatory acne of the face in women. skinmed. 2014;12:15–21. 29. graff dm, bosse gm, sullivan j. case report of methemoglobinemia in a toddler secondary to topical dapsone exposure. pediatrics. 2016;138:e1–2. 30. handler mz, chacon ah, shiman mi, schachner la. application of dapsone 5% gel in a patient with dermatitis herpetiformis. j. dermatol. case rep. 2012;6:132–3. 31. durham kc, hebert a. impact of 5% dapsone gel on the healing time of an ankle ulcer formed after achilles tendon rupture. j. am. acad. dermatol. [internet]. 2013;68:ab227. available from: http://www.embase.com/search/results?sub action=viewrecord&from=export&id=l70997 991%5cnhttp://dx.doi.org/10.1016/j.jaad.20 12.12.940%5cnhttp://sfx.library.uu.nl/utrec ht?sid=embase&issn=01909622&id=doi:10.1 016/j.jaad.2012.12.940&atitle=impact+of+5 %25+dapsone+gel+o 32. broussard kc, berger tg, rosenblum m, murase je. erosive pustular dermatosis of the scalp: a review with a focus on dapsone therapy. j. am. acad. dermatol. 2012;66:680=686. 33. frieling gw, williams nl, lim sj, rosenthal si. novel use of topical dapsone 5% gel for erythema elevatum diutinum: safer and effective. j. drugs dermatology. 2013;12:481–4. 34. babalola o, zhang j, kristjansson a, whitaker-worth d, mccusker m. granuloma faciale treated with topical dapsone: a case report. dermatol. online j. 2014;20. skin january 2018 volume 2 issue 1 copyright 2017 the national society for cutaneous medicine 43 35. jarratt m, jones t, chang-lin j, tong w, berk d, lin v, et al. safety and pharmacokinetics of once-daily dapsone gel, 7.5% in patients with moderate acne vulgaris. j. drugs dermatology. 2016;15:1250–9. 36. stein gold l, jarratt m, bucko a, grekin s, berlin j, bukhalo m, et al. efficacy and safety of once-daily dapsone gel, 7.5% for treatment of adolescents and adults with acne vulgaris: first of two identically designed, large, multicenter, randomized, vehicle-controlled trials. j. drugs dermatology. 2016;15:553–61. 37. eichenfield l, lain t, frankel e, jones t, chang-lin j, berk d, et al. efficacy and safety of once-daily dapsone gel, 7.5% for treatment of adolescents and adults with acne vulgaris: second of two identically designed, large, multicenter, randomized, vehicle-controlled trials. j. drugs dermatology. 2016;15:962–9. 38. draelos z, rodriguez d, kempers s, bruce s, peredo m, downie j, et al. treatment response with once-daily topical dapsone gel, 7.5% for acne vulgaris: subgroup analysis of pooled data from two randomized, doubleblind studies. j. drugs dermatology. 2017;16:591–7. 39. thiboutot d, kircik l, mcmichael a, cookbolden f, tyring s, berk d, et al. efficacy, safety, and dermal tolerability of dapsone gel, 7.5% in patients with moderate acne vulgaris: a pooled analysis of two phase 3 trials. j. clin. aesthet. dermatol. 2016;9:18–27. 40. allergan. phototoxicity test of dapsone gel in healthy volunteers [internet]. clinicaltrials.gov. 2014 [cited 2017 jul 23]. available from: https://clinicaltrials.gov/ct2/show/study/nc t02108483 41. brown p. clinical review: dapsone gel 7.5% [internet]. 2016. available from: https://www.fda.gov/downloads/drugs/deve lopmentapprovalprocess/developmentresour ces/ucm554649.pdf richard l. gallo, md1, susana raab2, margarita yatskayer2, stephen lynch2 1university of california san diego, department of dermatology, san diego, ca usa 2l’oréal research and innovation, clark, nj usa evaluation of the efficacy and tolerability of a topical facial serum in improving signs of aging introduction skin is the major reservoir for hyaluronic acid (ha) in the human body. ha is distributed throughout the epidermal and dermal compartments and plays an important role in cutaneous moisture control. decrease in ha levels, reduction in ha size and loss of ha functionality all directly impact the biomechanical properties of aging skin resulting in loss of elasticity and firmness. topically applied ha has traditionally been limited to use as a humectant due to lack of skin penetration. a topical product which could affect endogenous ha levels would be highly desirable as a cosmetic treatment. the goal of the present study was to evaluate the ability of a novel topical serum to modify histochemical markers associated with ha and improve visible signs of aging. methods table 1: expert evaluator graded skin attributes. all attributes showed statistical significant improvement at weeks 4, 8 and 12 vs. baseline. results table 2: percentages of favorable responses from self-assessment questionnaires. baseline week 12 figure 1: green color indicates ha binding protein conjugated to streptavidin and blue color indicates dapi counterstained cellular nuclei. fluorescent intensity was semi-quantitatively assessed on a 4-point scale. results of the expert grading showed statistically significant improvement in firmness, density, plumpness, sagginess, radiance, texture and skin tone evenness at weeks 4, 8 and 12 when compared to baseline (table 1). bioinstrumental measurement analysis showed statistically significant improvement in hydration (p<0.001), barrier properties of the stratum corneum (p=0.017) and skin density (p=0.012) at week 12 when compared to baseline. ha staining showed statistical significant increase in ha content after 12 weeks of product treatment (p=0.016) (figure 1). rt-pcr analysis showed statistical significant increase in has2 and col1a1 expression after 12 weeks of product use when compared to baseline (p=0.0008 & 0.0245, respectively). results from self-assessment showed favorable responses from the subjects (table 2). tolerability evaluations showed no statistical significant difference in the objective and subjective tolerance scores when compared to baseline. conclusions this topical formulation may have significant utility for improving signs of aging skin due to a decrease in ha level, reduction in ha size, and loss of ha functionality. in addition to the improvements observed in the clinical skin attributes, the study panel also showed improvements in skin hydration and barrier properties of the stratum corneum, skin density, increased ha content, and an increase in histochemical markers expression associated with ha such as has2 and col1a1. 4804 a 12-week, single center, clinical study was conducted on 59 females, ages 42-60, presenting with mild to moderate facial sagging, loss of firmness, rough skin texture, nasolabial fold wrinkles, marionette wrinkles and presence of fine lines/wrinkles in the crow’s feet area, including those with self-perceived sensitive skin. efficacy and tolerability evaluations were conducted and self-assessment questionnaires were administered at baseline, weeks 4, 8 and 12. bioinstrumental measurements were taken at baseline and at week 12. additionally, a subset of the study population (n=20, pre-menopausal women) had 3mm punch biopsies collected from 2 sites of the face at baseline and week 12 based on a computer-generated randomization. 50% of the biopsy samples were used for immunohistochemical staining/analysis and the remaining samples were used for quantitative rtpcr analysis of cd44, has2, has1, hyal1 and collagen 1a1. 0 10 20 30 40 50 60 70 80 90 100 product absorbs into the skin quickly product feels lightweight/not heavy on the skin skin feels hydrated skin feels more supple skin feels smoother skin feels firmer fine lines appear minimized/ reduced wrinkles appear minimized/ reduced skin appears more healthy skin tone appears more even overall, skin quality appears improved overall, skin feels improved overall satisfaction week 12 week 8 week 4 immediate 0 5 10 15 20 25 firmness density plumpness sagginess radiance tactile texture skin tone eveness m e a n % i m p ro v e m e n t fr o m b l week 4 week 8 week 12 fc17posterskinceuticalsgalloevaluationofefficacy.pdf acknowledgements: medical writing support was provided by prescott medical communications group (chicago, il) with financial support from ortho dermatologics; ortho dermatologics is a division of bausch health us, llc | 2020 fall clinical dermatology conference® for pas & nps • april 3-5, 2020 • orlando, fl synopsis ◾ acne is a common dermatologic issue in adolescence, though prevalence of acne in the adult population is increasing1 ◾ adult females are more likely to report acne than males across all age groups, with prevalence ranging from 50.9% (20-29 y) to 15.3% (≥50 y) in females and 42.5% (20-29 y) to 7.3% (≥50 y) in males2 ◾ adolescent and adult females are also more likely have worse acne-related quality of life3 ◾ a novel tazarotene 0.045% lotion formulation was developed for the treatment of acne, utilizing polymeric emulsion technology, resulting in a more uniform distribution of the active ingredient and hydrating excipients at the surface of the skin ◾ in a 12-week, randomized, double-blind, vehicle-controlled, parallel group, phase 2 study (nct02938494), tazarotene 0.045% lotion was superior to vehicle on inflammatory/ noninflammatory lesion count reductions in patients with moderate-to-severe acne4 ◾ in addition, tazarotene 0.045% lotion was as effective as the higher concentration tazarotene 0.1% cream (already approved for acne), but with fewer adverse events (aes)4 objective ◾ to evaluate the efficacy and safety of tazarotene 0.045% lotion in females and males methods ◾ in this phase 2 study, patients aged 12 years and older were randomized (2:2:1:1) to receive tazarotene 0.045% lotion, tazarotene 0.1% cream (tazorac), lotion vehicle, or cream vehicle • participants must have had a score of 3 (moderate) or 4 (severe) on the evaluator’s global severity score (egss) at the screening and baseline visit • in this study, cerave® hydrating cleanser and cerave® moisturizing lotion (l’oreal, ny) were provided as needed for optimal moisturization/cleaning of the skin ◾ a post hoc analysis was conducted in female and male patients, based on the following co-primary efficacy endpoints of the clinical trial: • mean absolute change in inflammatory and noninflammatory lesion counts from baseline to week 12 • treatment success, defined as percentage of patients achieving ≥2-grade reduction from baseline to week 12 in egss and a score of clear (0) or almost clear (1) ◾ safety and aes were also assessed results ◾ the intent-to-treat population included 210 participants (males, n=94; females, n=116) ◾ at week 12, tazarotene 0.045% lotion-treated females and males had significantly greater absolute least-squares mean reductions from baseline versus vehicle in noninflammatory lesion counts; only females had significant mean reductions versus vehicle in inflammatory lesion counts (figure 1) efficacy and safety of a novel tazarotene 0.045% lotion in females and males with moderate-to-severe acne figure 2. percent change from baseline in inflammatory and noninflammatory lesion counts in males and females (itt population, pooled) -3.2% -11.4% -40.7% -56.5% -4.0% -21.1% -32.8% -52.9% -14.5% -24.3% -39.5% -48.7% -70% -60% -50% -40% -30% -20% -10% 0% # * ) ( ' & % " + , *# ** *) m e a n p e rc e n t c h a n g e f ro m b a se lin e males taz 0.045% lotion (n=32) tazorac 0.1% cream (n=31) combined vehicle (n=31) baseline week 2 week 4 week 8 week 12 a. in�ammatory lesion count b. nonin�ammatory lesion count -18.2% -30.6% -52.9% -70.1% -13.6% -33.6% -52.3% -65.4% -19.8% -28.3% -39.4% -53.6% -70% -60% -50% -40% -30% -20% -10% 0% # * ) ( ' & % " + , *# ** *) m e a n p e rc e n t c h a n g e f ro m b a se lin e females taz 0.045% lotion (n=37) tazorac 0.1% cream (n=41) combined vehicle (n=38) baseline week 2 week 4 week 8 week 12 -17.6% -25.9% -39.7% -54.1% -6.9% -22.0% -33.1% -49.9% -5.4% -4.6% -24.0% -28.2% -70% -60% -50% -40% -30% -20% -10% 0% # * ) ( ' & % " + , *# ** *) m e a n p e rc e n t c h a n g e f ro m b a se lin e males taz 0.045% lotion (n=32) tazorac 0.1% cream (n=31) combined vehicle (n=31) baseline week 2 week 4 week 8 week 12 -11.6% -26.7% -42.6% -59.2% -11.0% -26.9% -44.7% -57.2% -5.8% -16.3% -36.4% -40.9% -70% -60% -50% -40% -30% -20% -10% 0% # * ) ( ' & % " + , *# ** *) m e a n p e rc e n t c h a n g e f ro m b a se lin e females taz 0.045% lotion (n=37) tazorac 0.1% cream (n=41) combined vehicle (n=38) baseline week 2 week 4 week 8 week 12 statistical analyses were not performed between treatment groups. itt, intent-to-treat; taz, tazarotene. table 1. treatment-emergent adverse events (safety population, pooled) males females participants, n (%) taz 0.045% lotion (n=31) tazorac 0.1% cream (n=30) combined vehicle (n=30) taz 0.045% lotion (n=37) tazorac 0.1% cream (n=41) combined vehicle (n=37) reporting any teae 6 (19.4) 9 (30.0) 4 (13.3) 4 (10.8) 10 (24.4) 5 (13.5) reporting any sae 0 0 0 0 0 0 discontinued due to teae 0 1 (3.3) 0 0 0 0 severity of teaes reported mild 5 (16.1) 6 (20.0) 4 (13.3) 1 (2.7) 6 (14.6) 5 (13.5) moderate 0 3 (10.0) 0 2 (5.4) 4 (9.8) 0 severe 1 (3.2) 0 0 1 (2.7) 0 0 relationship to study drug related 1 (3.2) 0 0 1 (2.7) 4 (9.8) 0 unrelated 5 (16.1) 9 (30.0) 4 (13.3) 3 (8.1) 6 (14.6) 5 (13.5) sae, serious adverse event; taz, tazarotene; teae, treatment-emergent adverse event. conclusions ◾ tazarotene 0.045% lotion was well tolerated and effective versus vehicle in reducing inflammatory and noninflammatory lesion counts in females and noninflammatory lesion counts in males ◾ tazarotene 0.045%-treated females had greater lesion count reductions and a greater percentage achieved treatment success than tazarotene-treated males, although these differences did not reach statistical significance ◾ taken together with the improved tolerability of tazarotene 0.045% lotion versus tazarotene 0.1% cream,4 this novel lotion formulation is a viable new treatment option that is as effective as cream with fewer aes references 1. skroza n, et al. j clin aesthet dermatol. 2018;11(1):21-25. 2. collier cn, et al. j am acad dermatol. 2008;58(1):56-9. 3. gorelick j, et al. j dermatol nurses assoc. 2015;7(3):154-162. 4. tanghetti ea, et al. j drugs dermatol. 2019;18(6):542. author disclosures hilary baldwin has served as advisor, investigator, and on speakers bureau for almiral, foamix, galderma and ortho dermatologics. lawrence green has served as speaker, consultant, or investigator for arcutis, abbvie, amgen, celgene, dermavant, jannsen, lilly, mc2, novartis, ortho dermatologics, sienna, sunpharma, and ucb. leon kircik has acted as an investigator, advisor, speaker, and consultant for ortho dermatologics. ashlie caronia has nothing to disclose. eric guenin is an employee of ortho dermatologics and may hold stock and/or stock options in its parent company. figure 1. mean change from baseline to week 12 in inflammatory and noninflammatory lesion counts in males and females (itt population, pooled) -16.5 -18.8 -13.8 -14.8 -30 -25 -20 -15 -10 -5 0 male female ls m e a n c h a n g e f ro m b a se li n e in�ammatory taz 0.045% lotion combined vehicle -21.6 -20.8 -12.0 -14.8 -30 -25 -20 -15 -10 -5 0 male female ls m e a n c h a n g e f ro m b a se li n e nonin�ammatory n=32 n=31 n=32 n=31n=37 n=38 n=37 n=38 *p<0.05 vs vehicle; **p<0.01 vs vehicle. itt, intent-to-treat; ls, least squares; taz, tazarotene. ◾ percent change from baseline in lesion counts by week are shown in figure 2 ◾ a larger percentage of tazarotene 0.045% lotion-treated females and males achieved treatment success versus vehicle (figure 3), although this difference was not significant ◾ there were no significant differences between the sexes on inflammatory/noninflammatory lesion counts or treatment success at week 12, regardless of treatment with tazarotene 0.045% lotion or tazarotene 0.1% cream ◾ treatment-emergent ae (teae) rates were higher in males than females for both tazarotene 0.045% lotion and tazarotene 0.1% cream; there were no differences with vehicle (table 1) figure 3. percentage of males and females with treatment success at week 12a (itt population, pooled) 12.5% 24.3% 9.7% 10.5% 0 10% 20% 30% 40% males females p e rc e n ta g e o f p a rt ic ip a n ts n=32 n=31 n=37 n=38 taz 0.045% lotion combined vehicle apercentage of participants achieving ≥2-grade reduction from baseline to week 12 in egss and a score of clear (0) or almost clear (1). comparisons between taz 0.045% lotion and combined vehicle were not significant. egss, evaluator’s global severity score; itt, intent-to-treat; taz, tazarotene. hilary baldwin, md1; lawrence green, md2; leon kircik, md3; ashlie m caronia, fnp 4; eric guenin, pharmd, phd, mph5 1the acne treatment and research center, morristown, nj; 2department of dermatology, george washington university school of medicine, washington, dc; 3indiana university school of medicine, indianapolis, in; physicians skin care, pllc, louisville, ky; and icahn school of medicine at mount sinai, new york, ny; 4 premier clinical research, spokane , wa; 5ortho dermatologics*, bridgewater, nj *ortho dermatologics is a division of bausch health us, llc. introduction • patients with moderate plaque psoriasis (i.e., 5% to 10% psoriasis-involved body surface area [bsa]1) often receive no treatment or are undertreated with topical monotherapy.2,3 • patients with moderate psoriasis often report substantial impairments in disease-related quality of life (qol), despite having lower psoriasis-involved bsa.3 • among the symptoms of psoriasis, pruritus is a key contributor to qol impairments.4 • apremilast, an oral, small-molecule phosphodiesterase 4 inhibitor,5 improved qol and disease severity, with acceptable tolerability, in phase iii clinical studies of patients with moderate to severe psoriasis.6-8 • evaluating apremilast in a phase iv trial of effi cacy and safety in patients with moderate plaque psoriasis (unveil; clinicaltrials. gov: nct02425826), the fi rst prospective, randomized, placebo (pbo)-controlled trial in systemicand biologic-naive patients with moderate plaque psoriasis, demonstrated that apremilast 30 mg twice daily (apr) was effective, generally well tolerated, and had a positive impact on qol during the 16-week, double-blind, pbo-controlled phase. • the improvements in qol and pruritus as well as treatment satisfaction are described for the open-label apr treatment phase (weeks 16 to 52) of unveil. methods patients key inclusion criteria • males or females ≥18 years of age • chronic plaque psoriasis for ≥6 months before screening • moderate plaque psoriasis at screening and baseline as defi ned by bsa of 5% to 10% and static physician’s global assessment (spga) of 3 (moderate) based on a scale ranging from 0 (clear) to 5 (very severe) • no prior exposure to systemic or biologic treatments for psoriasis, psoriatic arthritis, or any other condition that could affect the assessment of psoriasis key exclusion criteria • infl ammatory or dermatologic condition, including forms of psoriasis other than plaque psoriasis • topical therapy within 2 weeks or phototherapy within 4 weeks of randomization study design • unveil is a phase iv, multicenter, randomized, pbo-controlled, double-blind study (figure 1). • patients were randomized (2:1) to receive apr or pbo during weeks 0 to 16; patients in the pbo group were switched to apr at week 16. • all patients continued taking apr through week 52. • an unmedicated moisturizer was the only topical therapy permitted during the study. figure 1. unveil study design figure 2 dlqi pruritus vas apremilast 30 mg bid apremilast 30 mg bid‡placebo placebo-controlled phase open-label treatment phase safety observation ‒5 weeks week 16 week 52week 0 week 56 screen* dlqi pruritus vas tsqm dlqi pruritus vas tsqm ra n d o m iz e 1: 2§ clinicaltrials.gov: nct02425826 *screening up to 35 days before randomization. §all doses were titrated over the fi rst week of treatment. ‡at week 16, all placebo patients were switched to open-label apremilast 30 mg bid (with dose titration) through week 52. bid=twice daily. methods (cont’d) qol, pruritus, and treatment satisfaction assessments • patients completed the dermatology life quality index (dlqi), pruritus visual analog scale (vas), and treatment satisfaction questionnaire for medication (tsqm) version ii. qol • qol was assessed with the dlqi, a validated instrument that consists of 10 items pertaining to the skin and designed to assess qol in a dermatology clinical setting.9 • qol end points: – mean change from baseline in dlqi total score at week 16 and week 52 – proportion of patients with baseline dlqi >5 who achieved dlqi response (i.e., minimal clinically important difference [mcid], defi ned as ≥5-point improvement from baseline in dlqi total score among patients with baseline dlqi >5). pruritus • pruritus was assessed on a 100-mm vas ranging from “no itch” (0) to “itch as severe as can be imagined” (100). • pruritus end points included mean change from baseline in pruritus vas at week 16 and week 52. treatment satisfaction • treatment satisfaction was assessed using the tsqm version ii, a validated, self-administered, 11-question instrument designed to evaluate patient satisfaction with current treatment.10 – an algorithm is used to transform scores to a 0 to 100 scale for effectiveness, side effects, convenience, and global satisfaction, with higher scores indicating greater satisfaction. – mean tsqm scores for effectiveness, side effects, convenience, and global satisfaction were assessed at week 16 and week 52. safety assessments • safety was evaluated based on adverse events (aes), vital signs, clinical laboratory testing, and complete physical examinations. statistical analysis • qol, pruritus, and treatment satisfaction assessments were conducted for the intent-to-treat population, which included all randomized patients; safety assessments were conducted in all randomized patients who received ≥1 dose of study medication. • changes from baseline in dlqi total score and pruritus vas score at week 16 were compared between the apr and pbo groups using a 2-way analysis of covariance (ancova) model with treatment and site as factors and baseline value as a covariate. • the proportions of patients achieving a dlqi response at week 16 were compared between groups using a 2-sided cochran-mantel-haenszel test stratifi ed by site. • mean tsqm scores at week 16 were compared between treatment groups by 2-way analysis of variance (anova) with treatment and site as factors. • qol, pruritus, and treatment satisfaction parameters at week 52 were evaluated descriptively. • the last-observation-carried-forward (locf) methodology was used to impute missing values. • safety assessments were summarized using frequencies and percentages. results patients • a total of 221 patients were randomized to study treatment and constitute the intent-to-treat population; 185 patients (84%) completed the pbo-controlled phase (weeks 0 to 16) and 136/185 patients (74%) completed the apr treatment phase (weeks 16 to 52). • demographics and baseline disease characteristics were generally similar between treatment groups (table 1). – at baseline, mean dlqi total scores were comparable between treatment groups, and mean pruritus vas score was slightly higher in the pbo group. table 1. patient demographics and baseline disease characteristics characteristic pbo n=73 apr n=148 age, mean (sd), years 51.1 (13.7) 48.6 (15.4) male, n (%) 41 (56.2) 74 (50.0) body mass index, mean (sd), kg/m2 30.8 (6.5) 30.5 (7.4) duration of psoriasis, mean (sd), years 13.9 (12.6) 17.5 (13.9) bsa, mean (sd), % 7.1 (1.8) 7.2 (1.6) spga score=3 (moderate)*, n (%) 70 (95.9) 144 (97.3) dlqi total score, mean (sd) 11.1 (6.5) 11.0 (6.5) pruritus vas score, mean (sd), mm 60.0 (22.5) 55.0 (24.3) pasi score (0–72), mean (sd) 8.0 (3.2) 8.2 (4.0) *although the inclusion criterion was spga=3, patients with spga=4 were enrolled in error (n=4). pasi=psoriasis area and severity index. results (cont’d) effect of apr on qol • at week 16, improvement from baseline in dlqi total score was signifi cantly greater with apr than with pbo (−4.8 vs. −2.4; p=0.0008) (figure 2). • signifi cantly more patients with a baseline dlqi total score >5 who received apr vs. pbo achieved the dlqi mcid at week 16 (63.8% vs. 34.5%; p=0.0009) (figure 3). • at week 52, improvement in the dlqi total score was maintained in patients who were randomized to apr and then continued on apr during the open-label apr treatment phase (mean change from baseline: −4.4). • patients who switched from pbo to apr at week 16 achieved similar improvements in dlqi total score at week 52 (mean change from baseline: −5.1) (figure 2). • among patients who were initially randomized to apr at baseline, the percentage of patients who achieved dlqi mcid at week 16 was maintained over 52 weeks (figure 3). figure 2. improvements in dlqi total score –8 –7 –6 –5 –4 –3 –2 –1 0 pbo n=73 apr n=148 pbo/apr n=64 apr/apr n=121 week 16 week 52 –2.4 −4.8 −5.1 −4.4 m ea n ch an ge f ro m b as el in e in d lq i t ot al s co re * *p=0.0008 vs. pbo. error bars represent 95% confi dence intervals (cis). figure 3. proportion of patients achieving dlqi response 0 10 20 30 40 50 60 70 80 pbo n=58 apr n=116 pbo/apr n=54 apr/apr n=96 week 16 week 52 34.5 63.8 55.6 59.4 pa tie nt s ac hi ev in g d lq i m ci d (% ) * *p=0.0009 vs. pbo. error bars represent 95% cis. effect of apr on pruritus vas • at week 16, mean change from baseline in pruritus vas score was −19.2 mm in the apr group and −10.2 mm in the pbo group (p=0.0016) (figure 4). • the improvement in pruritus vas was maintained at week 52 in patients who continued on apr, and mean vas scores improved in those switched from pbo to apr (figure 4). results (cont’d) figure 4. improvement in pruritus vas score –50 –40 –30 –20 –10 0 pbo m ea n ch an ge f ro m b as el in e in p ru ri tu s va s, m m pbo and pbo/apr, n 69 68 59 61 57 55 50 44 39 apr and apr/apr, n 139 136 121 119 106 97 84 71 62 week 1 4 12 16 20 24 32 42 52 week 1 4 12 16 24 5232 42200 apr/apr pbo/aprpbo/apr locf –25.3 apr/apr locf –20.8 as-observed analysis. error bars represent 95% cis. treatment satisfaction • at week 16, treatment effectiveness, as measured by the tsqm, was signifi cantly greater with apr than with pbo (p<0.0001). global satisfaction also favored apr over pbo (p<0.0001), whereas satisfaction with side effects (p=0.34) and convenience (p=0.63) did not differ between treatment groups (figure 5). • at week 52, levels of satisfaction were maintained on all domains (figure 5). figure 5. treatment satisfaction measured using the tsqm m ea n ts qm s co re gr ea te r s at is fa ct io n m ea n ts qm s co re gr ea te r s at is fa ct io n week 52 75.0 65.7 78.5 66.9 77.3 72.775.5 71.8 0 10 20 30 40 50 60 70 80 90 100 side effects convenience pbo (n=73) apr (n=148) pbo/apr (n=64) apr/apr (n=121) week 52week 16 week 16 week 52 week 52week 16 week 16 38.8 48.7 57.3 63.2* * 57.7 59.2 54.1 59.9 0 10 20 30 40 50 60 70 80 90 100 effectiveness global satisfaction *p<0.0001 vs. pbo. error bars represent 95% cis. safety • the most common aes reported with apr treatment from 0 to 52 weeks included diarrhea, nausea, headache, and nasopharyngitis; most aes were mild or moderate in severity (table 2). • exposure-adjusted incidence rates (eair) per 100 patient-years did not increase with longer exposure up to 52 weeks. • no new safety or tolerability signals were observed up to 52 weeks. results (cont’d) table 2. overview of adverse events overview weeks 0 to 16 weeks 0 to 52 pbo n=73 apr n=147 apr* n=211 n (%) eair/100 pt-yrs n (%) eair/100 pt-yrs n (%) eair/100 pt-yrs ≥1 ae 35 (47.9) 262.3 92 (62.6) 459.8 142 (67.3) 242.7 ≥1 serious ae 0 (0) 0.0 3 (2.0) 7.4 10 (4.7) 6.8 ≥1 severe ae 1 (1.4) 4.9 3 (2.0) 7.5 5 (2.4) 3.4 ae leading to drug withdrawal 3 (4.1) 14.5 5 (3.4) 12.4 14 (6.6) 9.6 most common aes§ diarrhea 12 (16.4) 63.7 43 (29.3) 139.8 59 (28.0) 53.8 nausea 7 (9.6) 35.4 26 (17.7) 73.7 40 (19.0) 31.8 headache 8 (11.0) 42.4 30 (20.4) 89.2 32 (15.2) 24.9 nasopharyngitis 2 (2.7) 9.8 5 (3.4) 12.5 22 (10.4) 16.2 urti 3 (4.1) 14.8 10 (6.8) 25.2 15 (7.1) 10.7 vomiting 2 (2.7) 9.7 9 (6.1) 22.9 12 (5.7) 8.4 decreased appetite 4 (5.5) 19.6 6 (4.1) 15.3 11 (5.2) 7.7 *includes all patients exposed to apr, including those initially randomized to pbo and switched at week 16 to apr. §reported by ≥5% of patients in any treatment group; listed in order of incidence over 52-week period. pt-yrs=patient-years; urti=upper respiratory tract infection. eair/100 pt-yrs=exposure-adjusted incidence rate per 100 patient-years, calculated as (number of events*100)/(total exposure time [in years] of safety population). the exposure time for a patient without the specifi c event is the treatment duration; the exposure time for a patient with the specifi c event is the treatment duration up to the start date (inclusive) of the fi rst occurrence of the specifi c event. conclusions • apr improved qol and reduced pruritus at week 16 in systemicand biologic-naive patients with moderate plaque psoriasis (bsa 5% to 10%); these improvements were maintained over 52 weeks with continued apr treatment. • the benefi cial effects of apr on qol and pruritus were consistent with those previously reported in patients with moderate to severe plaque psoriasis in randomized phase iii trials.8,11 • global treatment satisfaction was greater with apr than with pbo at week 16, and satisfaction remained high over 52 weeks of apr treatment. • the safety and tolerability of apr were consistent with previous studies.6,7 no new safety or tolerability issues were observed with apr treatment up to 52 weeks. references 1. menter a, et al. j am acad dermatol. 2011;65:137-174. 2. armstrong aw, et al. jama dermatol. 2013;149:1180-1185. 3. lebwohl mg, et al. j am acad dermatol. 2014;70:871-881. 4. reich a, et al. acta derm venereol. 2010;90:257-263. 5. schafer ph, et al. cell signal. 2014;26:2016-2029. 6. papp k, et al. j am acad dermatol. 2015;73:37-49. 7. paul c, et al. br j dermatol. 2015;173:1387-1399. 8. thaci d, et al. j eur acad dermatol venereol. 2017;31:498-506. 9. finlay ay, et al. clin exp dermatol. 1994;19:210-216. 10. atkinson mj, et al. value health. 2005;8(suppl 1):s9-s24. 11. sobell jm, et al. acta derm venereol. 2016;96:514-520. acknowledgments the authors acknowledge fi nancial support for this study from celgene corporation. the authors received editorial support in the preparation of this report from amy shaberman, phd, of peloton advantage, llc, parsippany, nj, usa, funded by celgene corporation, summit, nj, usa. the authors, however, directed and are fully responsible for all content and editorial decisions for this poster. correspondence jerry bagel – dreamacres1@aol.com disclosures jb: abbvie, amgen, boehringer ingelheim, celgene corporation, janssen, leo pharma, eli lilly, novartis, pfi zer, and valeant – advisory board member, speaker, consultant, and/or research support; sun pharma – consultant. ml: mount sinai (which receives funds from boehringer ingelheim, celgene corporation, eli lilly, janssen/johnson & johnson, kadmon, medimmune/astrazeneca, novartis, pfi zer, and vidac). lsg: celgene corporation, leo pharma, novartis, pfi zer, and stiefel/glaxosmithkline – investigator and/or consultant. jmj: abbvie, amgen, celgene corporation, dermira, eli lilly, galderma, genentech, janssen, medimetriks, merck, novartis, pfi zer, promius, and topmd – research support, honoraria, consultant, and/or other support. jg & el: celgene corporation – employment. kcd: abbvie, amgen, boehringer ingelheim, bristol-myers squibb, celgene corporation, centocor/janssen, eli lilly, novartis, pfi zer, regeneron, stiefel, and xenoport – consultant, steering committee member, advisory board member, has received grants, and/or has received honoraria. bs: abbvie, amgen, astrazeneca, boehringer ingelheim, celgene corporation, dermira, eli lilly, forward pharma, janssen, leo pharma, maruho, medac, novartis, pfi zer, stiefel/glaxosmithkline, sun pharma, and ucb – honoraria as a consultant and advisory board member; abbvie, amgen, celgene corporation, eli lilly, janssen, merck, novartis, and pfi zer – payments (to the university of connecticut) as an investigator; corrona psoriasis registry – fees as a scientifi c director; abbvie and janssen – grant support (to the university of connecticut for fellowship program). effi cacy of apremilast on quality-of-life measures in patients with moderate plaque psoriasis (unveil phase iv study) jerry bagel, md1; mark lebwohl, md2; linda stein gold, md3; j. mark jackson, md4; joana goncalves, md5; eugenia levi, pharmd5; kristin callis duffi n, md6; bruce strober, md7 1psoriasis treatment center of central new jersey, east windsor, nj; 2icahn school of medicine at mount sinai, new york, ny; 3henry ford health system, west bloomfi eld, mi; 4university of louisville, forefront dermatology, louisville, ky; 5celgene corporation, summit, nj; 6university of utah, salt lake city, ut; 7university of connecticut, farmington, ct, and probity medical research, waterloo, ontario, canada presented at: the 2017 fall clinical dermatology conference; october 12–15, 2017; las vegas, nv. fc17postercelgenebagelefficacyapremilastmppunveil.pdf wintercdc 2018 rhap 52 week structure_electronic_22dec2017_a4size_lah ! 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" # " $ " % " & " " '( " ( & " & ( ! " ! " # " $% & '( ) *+ ) , ) . & % / ) ! 0 % . / ) *1 , 2 # *3 % 4 ) $' . ) )* + ,# . /)* + ,# . ,01 2 3 4 5 6,7 3 4 5 8 )* + ,! . /)* + ,! . ,01 2 3 4 $ 6,7 3 4 $ 8 ,%.2+)%*+7;11g+ /+aje <_v+`p8x <_v+`p8 as=bcfe <_v+`c8x <_v+`c8 as=bcde 7;11+l] <`-ba;\bc a;-bab\bc 7;11+l]mb ai-bae\_c a_-ba`\_c7;11+lhmlc+a16j@e aa-b`^\<c `^-b`i\acmicrosoft word skin introduction 061416.docx time for a new concept in the dermatology literature introducing skin: the journal of cutaneous medicinetm with the exponential increase in dermatology knowledge that is occurring, the challenge is to disseminate this new information to the clinician through a rapid, efficient and effective channel. many of the existing dermatologic journals are not taking full advantage of electronic communication methods and long publication lead times can result in delays in information dissemination. skin: the journal of cutaneous medicinetm has been designed to meet these challenges. skin is not just a new, peer-reviewed dermatology journal, but also a novel concept designed to more rapidly disseminate diagnostic, therapeutic and management techniques and trends in the specialty. skin does not seek to merely copy traditional paper formats. rather, our aim is to amplify the distribution of scientific information from peer-reviewed submitted papers, and clinical posters and oral presentations at major conferences (that typically have no formal method for publication or that currently may take many months to disseminate) quickly to our dermatology colleagues to facilitate integration into their clinical setting. for all of these reasons, skin: the journal of cutaneous medicinetm does not aim to be just another dermatology journal, but rather begin a paradigm shift that will more rapidly and thoroughly present free, easily accessible and relevant material that will enhance dermatologists’ practices. with the above vision and through the use of the online journal format to accelerate getting new information to you, skin has the ability to achieve these goals. the editors of skin hope that you will find the information presented to be informative and useful and look forward to your thoughts and ideas of how we can make skin optimize its value to you. editors-in-chief mark lebwohl md professor and chairman, dermatology, icahn school of medicine at mount sinai, new york, ny roger ceilley md clinical professor of dermatology, university of iowa school of medicine, des moines, ia james del rosso do adjunct clinical professor, touro university college of osteopathic medicine, henderson, nv editors brian berman md, phd professor emeritus, dermatology and cutaneous surgery, university of miami miller school of medicine, miami, fl robert thomas brodell md professor and chair of department of dermatology, university of mississippi, jackson, ms m. shane chapman md chair of dermatology, dartmouth-hitchcock medical center, hanover, nh clay cockerell md clinical professor of dermatology and pathology, director of dermatopathology, university of texas southwestern, dallas, tx seemal desai md clinical assistant professor, department of dermatology, university of texas southwestern medical, dallas, tx scott dinehart md director, arkansas skin cancer center, little rock, ar boni elewski md james e. elder, md, endowed professor for graduate education and chair, university of alabama at birmingham, al david pariser md professor of dermatology, eastern virginia medical school, norfolk, va darrell s rigel md, ms clinical professor of dermatology, new york university school of medicine, new york, ny theodore rosen md professor of dermatology, baylor college of medicine, chief of va dermatology service, va medical center, houston, tx kenneth tomecki md vice chairman, dermatology, cleveland clinic, cleveland, oh resident/fellow editorial board aaron s. farberg md, icahn school of medicine at mount sinai, new york, ny alex m. glazer md, university of arizona, tucson, az richard r. winkelmann do, ohio university, columbus, oh resident/medical student associate editors michael cameron md, university of colorado, department of dermatology, denver, co rebeca teplitz, new york institute of technology college of osteopathic medicine, old westbury, ny background • acne vulgaris (av) is a common skin disease that affects adolescents and can persist into adulthood1 • the mainstay of treatment for av is systemic tetracyclines, such as doxycycline and minocycline2 • fmx101 4% is a novel topical foam formulation of minocycline. it has been shown to be an effective and well-tolerated treatment for moderate-to-severe av in a phase 2 clinical trial3 • two phase 1 studies were conducted to characterize minocycline pharmacokinetics (pk) and safety following multiple-dose administration of fmx101 4% minocycline foam in adult (study fx2014-03) and pediatric (study fx2016-21) patients with moderate-to-severe av methods • 2 phase 1, single-center, nonrandomized, open-label studies (figure 1, table 1) • adults (age 18 to 35 years) or pediatric subjects (age 9 years to 16 years, 11 months) with moderate-to-severe av – adult study (fx2014-03) first received a single 1-mg/kg oral dose of oral extendedrelease minocycline hcl tablet (solodyn®). then, after 10 days, they received a once-daily topical application of 4 g fmx101 4% to the face, neck, upper chest, upper back, shoulders, and upper arms for 21 days – pediatric study (fx2016-21) received once-daily topical application of 4 g fmx101 4% to the face, neck, upper chest, upper back, shoulders, and upper arms for 7 days figure 1. study design methods table 1. inclusion criteria and assessments adult study (fx2014-03) pediatric study (fx2016-21) inclusion criteria • healthy males/females aged 18–35 years • moderate-to-severe facial av (additionally affecting ≥2 regions of neck, upper chest, upper back, or arms) • bmi within 18.5-29.9 kg/m2 ; body weight within 48.0-128.0 kg • not pregnant, lactating, or planning a pregnancy during study • healthy males/females aged 9 years to 16 years, 11 months – subjects <12 years: mild facial acne and acne of limited extent – subjects 12–16 years: moderate-to-severe av based on 5-point iga scale and acne affecting ≥1 of the following: neck, upper chest, upper back, or arms • sexually inactive, sterile, or using contraception blood sampling for drug concentration • predose through 96 hours after administration of oral minocycline • predose through 24 hours after fmx101 4% application on days 1, 12, and 21 • prior to scheduled application on days 6, 9, 10, 11, and 16 • on and after day 21, at 24 hours (day 22), 48 hours (day 23), 72 hours (day 24), and 96 hours (day 25) from last application of fmx101 4% • on day 7, after 3, 12, 16, and 24 hours from last application of fmx101 4% pharmacokinetic analyses • pk parameters were calculated using noncompartmental methods • pk parameters included auc 0-inf, auc 0-tau , auc 0-tldc , c max , c 24 , t max , t 1/2 , and accumulation ratio • pk parameters were calculated using noncompartmental methods • pk parameters included auc 0-tau , c max , and c 24 statistical analyses • geometric mean was calculated for auc 0-inf , auc 0-tau , auc 0-tldc , and c max • geometric mean was calculated for auc 0-tau and c max auc 0-inf =auc from 0 to infinity. auc 0-tau =auc during the 24-hour dosing interval. auc 0-tldc =auc from 0 to time of last determinable concentration. c 24 =plasma minocycline concentration 24 hours after fmx101 4% application. c max =maximum plasma drug concentration. t 1/2 =terminal phase half-life. t max =time of maximum measured plasma drug concentration. bmi=body mass index. iga=investigator’s global assessment. results baseline demographics • baseline characteristics are shown in table 2 • all adult subjects had moderate-to-severe av • a majority of pediatric subjects (90%) had moderate av, and 1 subject had mild av table 2. baseline characteristics adult study (fx2014-03) (n=30) pediatric study (fx2016-21) (n=20) mean age (range), yr 22.6 (18-30) 13.2 (10-16) gender, n (%) male/female 12 (40) / 18 (60) 9 (45) / 11 (55) race, n (%) white black or african american 27 (90) 3 (10) 7 (35) 13 (65) ethnicity, n (%) hispanic/latino non-hispanic/latino 11 (36.7) 19 (63.3) 2 (10) 18 (90) pharmacokinetics – adults • the mean plasma concentration of oral minocycline in adult subjects reached c max by 3 hours after administration, followed by a log-linear decrease in concentration for the remaining 96-hour sample period • the mean plasma minocycline concentration of fmx101 4% increased until 8–14 hours (median t max value) on days 1, 12, and 21 • figure 2 shows a comparison of mean plasma minocycline concentrations during the first 24 hours after a single dose of oral minocycline and after topical applications of fmx101 4% at 3 timepoints in adult subjects • in adult subjects, oral minocycline treatment had a geometric mean c max of 850 ng/ml, while topical application of 4 g fmx101 4% in adults had a geometric mean c max ranging from 1.109–1.539 ng/ml (days 1-2, days 12-13, and days 21-25) • steady state was achieved on day 6 of treatment figure 2. mean plasma minocycline concentration over the first 24 hours following a single dose of oral minocycline and topical application of fmx101 4% (semi-log scale) in adult subjects (study fx2014-03) results: pharmacokinetics – adults • in adults, minocycline exposure with daily topical application of fmx101 4% for 21 days was 730 to 765 times lower than that with oral minocycline (table 3) table 3. summary of minocycline relative bioavailability with oral minocycline administration (reference) and topical application of fmx101 4% (test) at day 12 and day 21 (study fx2014-03) fmx101 4% vs oral minocycline n geometric meana geometric lsm test/reference ratio,b % (90% ci) 1/gmr fmx101 4% (test) oral minocycline (ref) day 12 c max 29 1.06 846 0.126 (0.100, 0.159) 794 day 21 c max 30 1.11 850 0.131 (0.113, 0.151) 763 day 12 aucc 29 20.06 14976 0.134 (0.110, 0.163) 746 day 21 aucd 30 20.07 15060 0.137 (0.121, 0.156) 730 ªgeometric mean of oral minocycline and fmx101 4% based on lsm. bgeometric lsm ratio and the associated 90% ci were back-transformed point estimates and the associated 90% ci. cday 12 auc 0-tau for fmx101 4% vs auc 0-inf for oral minocycline. dday 21 auc 0-tau for fmx101 4% vs auc 0-inf for oral minocycline. ci=confidence interval; lsm=least squares mean; gmr=geometric mean ratio. pharmacokinetics – pediatrics • in pediatric subjects, the overall plasma concentrations of minocycline following the application of fmx101 4% once daily for 7 days were relatively constant over day 7 (~2.5 ng/ml) (figure 3) figure 3. mean plasma concentrations of minocycline following application of fmx101 4% once daily for 7 days in pediatric subjects (study fx2016-21) results: pharmacokinetics – pediatrics -5 0 5 10 15 20 25 0 3 12 16 24 pl as m a m in oc yc lin e c on ce nt ra tio n (n g/ m l) ± sd hours post-day 7 administration 9 11 years 12 14 years 15 16 years, 11 months overall lloq lloq=lower limit of quantification; sd=standard deviation. lloq=lower limit of quantification; sd=standard deviation. • there were no substantial differences in mean concentrations of minocycline among the 3 pediatric cohorts (table 4) – across all cohorts, the geometric mean c max value was 2.4 ng/ml table 4. pharmacokinetic parameters of minocycline in plasma in pediatric acne subjects treated with fmx101 4% (study fx2016-21) age group n geometric mean t max (hr)ac max (ng/ml) auc 0-tau (ng*hr/ml) c 24 (ng/ml) 9–11 years 6 3.522 68.175 2.933 12 (0,24) 12–14 years 8 2.250 42.167 1.998 20 (0,24) 15–16 years, 11 months 6 1.735 35.067 1.302 6 (0,24) overall 20 2.381 46.087 1.972 12.1 (0,24) amedian (minimum, maximum) shown for t max . safety • in both adult and pediatric subjects, daily application of fmx101 4% was found to be safe and well tolerated (table 5) – no adult or pediatric subjects experienced a serious treatment-emergent adverse event (teae), treatment-related teaes, or a teae leading to withdrawal from the study – 9 adult subjects in the fmx101 4% group reported 1 or more teaes; all were mild or moderate in intensity (fx2014-03) – a single pediatric subject experienced 2 unrelated teaes (nausea and vomiting) (fx2016-21) table 5. overall summary of teaes following administration of oral minocycline and topical application of fmx101 4% in adult and pediatric subjects adult study (fx2014-03) pediatric study (fx2016-21)   oral minocycline (n=30) fmx101 4% (n=30) fmx101 4% (n=20) subjects with any teae, n (%) 2 (6.7) 9 (30.0) 1 (5.0) dysmenorrhea 0 2 (6.7) nasal congestion 0 2 (6.7) rhinorrhea 0 2 (6.7) asthma 0 1 (3.3) bronchitis 0 1 (3.3) cough 1 (3.3) 0 dermatitis contact 0 1 (3.3) headache 1 (3.3) 0 oropharyngeal pain 0 1 (3.3) pharyngitis streptococcal 0 1 (3.3) respiratory tract congestion 0 1 (3.3) tonsillitis 0 1 (3.3) nausea 1 (5.0) vomiting 1 (5.0) pharmacokinetic evaluation of once-daily topical 4% minocycline foam in adult and pediatric subjects with moderate-to-severe acne in two phase 1 studies terry m. jones, md1; herman ellman, md2; tina devries, phd2 1j&s studies, inc., college station, texas, usa; 2foamix pharmaceuticals, inc., bridgewater, new jersey, usa references 1. picardo m, et al. dermatol ther (heidelb). 2017;7:43-52. 2. zaenglein al, et al. j am acad dermatol. 2016;74:945-973. 3. shemer a, et al. j am acad dermatol. 2016;74:1251-1252. disclosure: foamix pharmaceuticals, inc., sponsored this study. conclusions • in adult subjects, mean minocycline auc and c max values were substantially lower following the daily topical application of 4 g fmx101 4% for 21 days in comparison with a single dose of oral minocycline (~1 mg/kg) • there was no evidence of accumulation in adult subjects receiving daily topical application of fmx101 4% for up to 21 days • in pediatric subjects, mean minocycline cmax and auc values following the daily topical application of 4 g fmx101 4% for 7 days were 2.4 ng/ml and 46.1 ng*hr/ml, respectively; these values were comparable to those seen in adults, 1.5 ng/ml and 20.1 ng*hr/ml, respectively, indicating similar minimal systemic exposure • pediatric subjects in all 3 age cohorts had similar levels of minocycline (~2.5 ng/ml) across the dosing interval with daily application of fmx101 4% for 7 days • once-daily topical application of fmx101 4% for 7 days and 21 days was shown to be safe and well tolerated in pediatric and adult subjects, respectively acknowledgment: p-value communications provided editorial support. � � � � � � � � � � � � � � � � � � � 1 ≥ ≥ ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± • • • • • ≤ • > • < • • fc17posterbiofronteradirschkadaylightphotodynamic.pdf copyright 2017 the national society for cutaneous medicine reprint requests should be sent to jofskin@gmail.org. skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 105 brief articles frequently debrided and misdiagnosed: post-surgical pyoderma gangrenosum lindsey w fraser, md1, stephanie a castillo, ba2, shabnam momtahen, md2,3, michael s chapman, md, mba1,2 1department of dermatology, dartmouth-hitchcock medical center, lebanon, nh 2geisel school of medicine at dartmouth, hanover, nh 3department of pathology and laboratory medicine, dartmouth-hitchcock medical center, lebanon, nh in many surgical specialties, minimally invasive procedures have become the mainstay of therapeutic interventions. while this has decreased the rates of many postoperative adverse events, pyoderma gangrenosum in the post-surgical setting continues to occur and remains well documented (1, 2). post-surgical pyoderma gangrenosum (pspg) is characterized by an expanding surgical wound, painful central ulceration with an undermined, gray border and necrotic base. pg is estimated to occur in 3 to 10 cases per million population worldwide each year, and individuals aged 25 to 54 years are most frequently affected. (3). a female predilection has been reported for pspg (2). this condition is frequently misdiagnosed as post-operative infection. we report a case of an 80-year-old caucasian female with multiple comorbidities, including a history of low grade, transfusion-dependent myelodysplastic syndrome (mds) without additional treatment, hypertension, and chronic systolic congestive heart failure with an ejection fraction of 42%, who was admitted to the hospital for a myocardial infarction. she underwent cardiac catheterization through her right femoral artery, and within the week following the procedure, she developed a red papule at the procedure site which then ulcerated. she was treated for a presumed post-operative wound infection with multiple courses of iv vancomycin, piperacillin/tazobactam, post-surgical pyoderma gangrenosum is rare. on average it develops 10 days after a surgical procedure. this timeframe is similar to post-operative wound infections, including post-operative necrotizing fasciitis. consequently, post-surgical pyoderma gangrenosum is frequently misdiagnosed as an infection, leading to detrimental surgical debridement, unnecessary antibiotic use, and delay of proper treatment. herein, we describe a case of pyoderma gangrenosum of the right inguinal crease following percutaneous coronary catheterization and provide a literature review. abstract introduction case report skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 106 figure 1: right inguinal fold with deep, necrotic ulceration. clindamycin, surgical debridement, and wound vac placement. wound cultures were negative and the patient was afebrile throughout her hospital course. the ulceration continued to enlarge. after four weeks, a second debridement was performed, and a biopsy was taken during debridement. dermatology was consulted. examination of the right inguinal fold revealed a large, deep, necrotic ulceration with a “vegetative” irregular, erythematous border (figure 1). the ulcer and surrounding tissue were extremely painful. histopathology revealed extensive ulceration in association with a central zone of necrotizing suppurative inflammation with sheets of neutrophils and inflammatory debris. a peripheral vascular reaction defined by perivascular and intramural lymphocytic infiltrates with a peripheral neutrophilic component, although without fibrinoid necrosis, was also noted (figure 2). special stains (gram, pas, afb and fite) were negative for gram +/bacteria, fungi, and acid-fast mycobacterial organisms. a diagnosis of post-surgical pyoderma gangrenosum was made. intravenous 1 gram methylprednisolone was given for 3 days, followed by transition to 60 mg prednisone daily. in conjunction with cardiology, the decision was made to initiate infliximab 5mg/kg due to its fast onset of action and weight-based dosing. cardiology deemed the patient’s heart failure to be stable, and the rapid expansion of the ulceration was resulting in severe pain and suffering on behalf of the patient. the patient was transferred to a rehabilitation facility and died within three weeks. the cause of death was not determined. patients with pspg are commonly admitted to a surgical subspecialty service. these services are accustomed to diagnosing and treating post-operative wound infections and other wound complications. pspg initially presents as erythema encompassing an incision or suture lines, which develops into figure 2: histology showing perivascular and intramural lymphocytic infiltrates with a peripheral neutrophilic component, although without fibrinoid necrosis. discussion skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 107 punctate ulcerations that later coalesce into a large painful ulcer with a rolled or undermined border. by contrast, necrotizing fasciitis tends to present as a patchy skin discoloration, usually dusky red or violaceous, with poorlydefined expanding erythema that develops into a tense edema with bullae, vesicles, or necrosis (4). patients with necrotizing fasciitis may rapidly decline, becoming febrile, systemically unstable and septic. both necrotizing fasciitis and pspg are excruciatingly painful, which is out of proportion to their symptoms. when pspg is mistaken for a wound infection, debridement, skin grafting, and local flap coverage may be undertaken, which induces a pathergic response that exacerbates the ulceration and causes expansion. in a retrospective study of 18 patients with pspg seen at the mayo clinic over a 20-year period, debridement was performed in 11 (61%) of the patients (2). pspg should be suspected in the post-operative setting whenever the clinical findings of pspg are present, painful ulceration occurs, and when ulceration is progressing in spite of antibiotic therapy and surgical debridement. a wound culture is highly unreliable because a negative culture does not rule out an infection while a positive culture may reflect low levels of bacterial colonization in the context of pspg (5). in our case, the patient’s history of myelodysplasia served as another helpful diagnostic clue. myelodysplastic syndrome (mds) consists of heterogeneous clonal hematopoietic stem cell malignancies that are driven by immune dysregulation, and which confer increased risk of progression to acute myelogenous leukemia (6). while pyoderma gangrenosum (pg) is idiopathic, over 50% of patients with pg have a comorbid systemic disease, including mds, inflammatory bowel disease, and rheumatoid arthritis (2,4,5). pspg is associated to a lesser degree with systemic disease than other types of pg, however hematologic dyscrasias have been reported to be the most common condition in this subtype (2,4). the distinction of pg from other ulcerative processes with dermal neutrophilia based on histology alone is challenging and, at times, impossible. therefore, a detailed clinical history and solid knowledge of the underlying systemic disease or the associated processes is essential to reach the correct diagnosis. histologically, pg may closely mimic sweet’s syndrome, which is a common manifestation of underlying hematopoietic disorders, however, clinical features make the distinction possible. as the lesions of pg are frequently follicular-based, other causes of necrotizing pustular follicular reactions with associated vasculopathy should be considered in the differential diagnoses. these include rheumatoid vasculitis, mixed cryoglobulinemia or behcet’s disease. however, these conditions are often associated with neutrophil-predominant necrotizing vasculitis in contrast to pg, which often shows a mononuclear-predominant non-necrotizing vascular reaction (7). there is a dearth of evidence-based literature regarding effective therapies for pg. however, the use of immunosuppressive therapy with systemic corticosteroids and cyclosporine, either individually or in combination, is well established as first line therapy in the literature (2). effective treatment of pg with topical corticosteroids and tacrolimus has also been reported, but these are usually restricted to limited and localized cases of pg (8,9). dapsone has demonstrated efficacy in the treatment of pg in children, with a success rate of approximately 80% (10). effective suppression of pathergy using anti-tumor necrosis factor agents such as infliximab, skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 108 etanercept, and adalimumab have also been reported (11,12). alternative treatment options include hyperbaric oxygen, methotrexate, cyclophosphamide, mycophenolate mofetil, sulfasalazine, and azathioprine (1). pg has a good prognosis when diagnosed and treated immediately; however, if appropriate therapy is delayed, the prognosis worsens and may lead to sepsis and death (5). while pg is well documented in the dermatology literature, it is less frequently reported in the surgical or cardiology literature. this underscores the importance of increasing awareness of pg as a differential diagnosis for wound infections among nondermatology specialists and surgeons. as this condition can be easily misdiagnosed and incorrectly treated, early consultation with dermatology is highly recommended conflict of interest disclosures: none. funding: none. corresponding author: lindsey w fraser, md dartmouth-hitchcock medical center lebanon, nh lindsey.w.fraser@hitchcock.org references: 1. almukhtar r, armenta a, martin j, et al. delayed diagnosis of post-surgical pyoderma gangrenosum: a multicenter case series and review of the literature. international journal of surgery case reports. 44 (2018), 152-156. 2. tolkachjov sn, et al. postoperative pyoderma gangrenosum (pg): the mayo clinic experience of 20 years from 1994 through 2014. j. am. acad. dermatol., 73 (4) (2015), pp. 615-622 3. monari p et al. epidemiology of pyoderma gangrenosum: results from an italian prospective multicentre study. int wound j. 2018 dec; 15(6): 875-879. 4. tolkachjov sn et al. postoperative pyoderma gangrenosum: a clinical review of published cases. mayo clin proc. 2016 sep; 91(9): 1267-79. 5. ogata k et al. pyoderma gangrenosum in an abdominal surgical site: a case report. surg case rep. 2015 dec; 1:122. 6. wang c et al. immune dysregulation in myelodysplastic syndrome: clinical features, pathogenesis, and therapeutic strategies. crit rev oncol hematol. 2018 feb; 122. 123-132. 7. crowson an, mihm mc jr, magro c. pyoderma gangrenosum: a review. j cutan pathol. 2003 feb; 30(2): 97-107. 8. le cleach l et al. is topical monotherapy effective for localized pyoderma gangrenosum? arch dermatol. 2011; 147: 101-3. 9. thomas et al. clinical outcomes and response of patients applying topical therapy for pyoderma gangrenosum: a prospective cohort study. j am acad dermatol. 2016 nov; 75(5): 940-949. 10. kechichian e et al. pediatric pyoderma gangrenosum: a systemic review and update. int j dermatol. 2017 may; 56(5): 486-495. 11. leiphart pa et al. suppression of pathergy in pyoderma gangrenosum with infliximab allowing for successful tendon depridement. jaad case rep 2017 dec 20; 4(1): 98-100. 12. niamtu j 3rd. pyoderma gangrenosum after facelift and otoplasty surgery: case presentations and literature review. j oral maxillofac surg. 2018 oct [epub ahead of print]. mailto:lindsey.w.fraser@hitchcock.org 1department of dermatology, dartmouth-hitchcock medical center, lebanon, nh 2geisel school of medicine at dartmouth, hanover, nh 3department of pathology and laboratory medicine, dartmouth-hitchcock medical center, lebanon, nh long-term efficacy of brodalumab for the treatment of moderate-to-severe psoriasis: data from a pivotal phase 3 clinical trial alan menter,1 jeff sobell,2 jonathan i. silverberg,3 mark lebwohl,4 shipra rastogi,5 radhakrishnan pillai,6 robert j. israel7 1baylor university medical center, dallas, tx; 2skincare physicians, chestnut hill, ma; 3northwestern university feinberg school of medicine, chicago, il; 4icahn school of medicine at mount sinai, new york, ny; 5ortho dermatologics, bridgewater, nj; 6dow pharmaceutical sciences (a division of valeant pharmaceuticals north america llc), petaluma, ca; 7valeant pharmaceuticals north america llc, bridgewater, nj winter clinical dermatology conference hawaii® • january 12-17, 2018 • lahaina, hi introduction • brodalumab is a fully human anti–interleukin-17 receptor a monoclonal antibody that antagonizes the action of specific inflammatory cytokines involved in psoriasis1 • three pivotal phase 3 clinical trials demonstrated the efficacy and safety of brodalumab through 52 weeks in patients with moderate-to-severe psoriasis (amagine-1/-2/-3)1,2 – brodalumab exhibited superior efficacy vs ustekinumab, with a faster onset of response and a similar safety profile – data in this poster are from amagine-2 objective • to evaluate the long-term efficacy and safety of brodalumab in patients with moderate-to-severe plaque psoriasis through 120 weeks methods study design • amagine-2 was a 52-week, randomized, double-blind, placebo and active comparator–controlled clinical trial – data from this analysis were derived from a long-term open-label extension study through 120 weeks • patients received brodalumab 210 or 140 mg every 2 weeks (q2w), ustekinumab, or placebo during a 12-week induction phase, which was followed by a maintenance phase through week 52 (figure 1) • during the maintenance phase, patients receiving brodalumab were re-randomized to receive a different dose and interval of brodalumab (140 or 210 mg q2w, q4w, or q8w), patients receiving ustekinumab continued on ustekinumab, and patients receiving placebo were switched to brodalumab 210 mg q2w – at week 16, patients from all brodalumab and ustekinumab groups without adequate response (single static physician’s global assessment [spga] score ≥3 or persistent spga score of 2 over ≥4 weeks) were eligible for rescue with brodalumab 210 mg q2w • at week 52, patients who received brodalumab during the maintenance phase continued to receive their maintenance dose of brodalumab, and patients who received ustekinumab switched to brodalumab 210 mg q2w • efficacy data are for patients who received brodalumab 210 mg q2w (the us food and drug administration–approved dose) at any point through week 120 of the long-term extension phase, including patients who received – placebo during the induction phase – ustekinumab during the maintenance phase – brodalumab 140 or 210 mg q2w during the maintenance phase – rescue treatment during the maintenance phase • a further subanalysis of efficacy data from patients who received any dose of brodalumab in the induction phase and brodalumab 210 mg q2w during the maintenance and long-term extension phases is presented • safety data are for all patients who received ≥1 dose of brodalumab at any point in the study endpoints/assessments • skin clearance was monitored by the spga and the psoriasis area and severity index (pasi) • safety was assessed by monitoring exposure-adjusted treatmentemergent adverse event rate per 100 patient-years results patient demographics and baseline disease characteristics • most patients were male, with a mean (standard deviation) age of 44.6 (12.8) years (table 1) • a total of 1392 patients entered the long-term extension phase on brodalumab 210 mg q2w, and 1282 patients had a valid measurement at week 52 efficacy • skin clearance response rates at weeks 52 and 120 were similar in patients who received brodalumab 210 mg q2w during the long-term extension (figure 2) • in patients who received any dose of brodalumab in the induction phase and brodalumab 210 mg q2w during the maintenance and long-term extension phases, rates of achieving spga 0/1, pasi 75% improvement (pasi 75), pasi 90, and pasi 100 were maintained from weeks 54 to 120 (figure 3) • patients who received continuous brodalumab throughout the entire study had a higher rate of achieving pasi 100 compared with patients who received placebo or ustekinumab during the induction phase safety • a total of 1790 patients received ≥1 dose of brodalumab, with a total time of exposure of 3228.5 years (table 2) • the safety profile of brodalumab was consistent with that observed in shorter-term studies, and no new safety signals were identified figure 1. amagine-2 study design. ► ► ► ► day 1 week 12 week 16 week 52 ustekinumab 210 mg q2w 210 mg q2w ustekin umabplacebo ustekin umabustekinumab brodalumab 210 mg q2w induction maintenance long-term extension 210 mg q2w 140 mg q2w 140 mg q4w 140 mg q8w brodalumab 140 mg q2w r 2:2:2:1 210 mg q2w (rescue) q2w, every 2 weeks (with an additional loading dose 1 week after initiation of brodalumab); q4w, every 4 weeks; q8w, every 8 weeks; r, randomized. acknowledgments: medical writing support was provided by medthink scicom and was funded by ortho dermatologics. this study was sponsored by amgen inc. author disclosures: the authors disclose past or current financial relationships with the following companies: menter – abbvie, allergan, amgen, anacor, boehringer ingelheim, celgene, dermira, eli lilly, galderma, janssen biotech, leo pharma, merck & co, neothetics, novartis, pfizer, regeneron, symbio/maruho, vitae, and xenoport; sobell – abbvie, amgen, celgene, janssen, lilly, merck, novartis, and regeneron; silverberg – abbvie, eli lilly, galderma, glaxosmithkline, kiniksa, leo, menlo, pfizer, realm-1, regeneron-sanofi, and roivant; lebwohl – amgen, anacor, boehringer ingelheim, celgene, eli lilly, janssen biotech, kadmon, leo pharma, medimmune, novartis, pfizer, sun pharmaceutical industries, and valeant pharmaceuticals north america llc; rastogi – ortho dermatologics and valeant pharmaceuticals north america llc; pillai – dow pharmaceutical sciences (a division of valeant pharmaceuticals north america llc); and israel – valeant pharmaceuticals north america llc. references: 1. lebwohl et al. n engl j med. 2015;373:1318-1328. 2. papp et al. br j dermatol. 2016;175:273-286. conclusions • treatment with brodalumab resulted in substantial psoriatic lesion clearing for >2 years in most patients with moderate-to-severe psoriasis • skin clearance response rates, as determined by spga 0/1, pasi 75, pasi 90, and pasi 100, were maintained from weeks 52 to 120 in patients who received brodalumab 210 mg q2w • patients receiving continuous treatment with brodalumab had higher rates of pasi 100 compared with patients who received placebo or ustekinumab during the induction phase pasi 75 90.6 88.4 pasi 90 77.6 76.8 pasi 100 53.3 56.2 r es po nd er s, % 60 0 40 20 80 100 spga 0/1 79.2 1015 597 1162 689 995 598 683 438 n 76.6 week 52 (n=1282) week 120 (n=779) figure 2. skin clearance response rates at weeks 52 and 120 in patients who received brodalumab 210 mg q2w during the long-term extension. error bars show the 95% confidence interval. n, number of patients who were responders; pasi 75, 90, and 100, psoriasis area and severity index 75%, 90%, and 100% improvement; spga 0/1, static physician’s global assessment score of 0 or 1. long -term extension 86.5% 79.2% 76.4% 59.0% 0 10 20 30 40 50 60 70 80 90 100 0 20 40 60 80 100 120 140 r es po nd er s, % weeks spga 0/1 pasi 75 pasi 90 pasi 100 120 week n1= 334 334 316 310 290 291 285 280 234 178 0 12 24 36 52 72 84 96 108 figure 3. patients who received continuous brodalumab and achieved spga 0/1, pasi 75, pasi 90, and pasi 100 response through week 120. error bars show the 95% confidence interval. n1, number of patients who had a valid measurement value at the specified week; pasi 75, 90, and 100, psoriasis area and severity index 75%, 90%, and 100% improvement; spga 0/1, static physician’s global assessment score of 0 or 1. table 1. baseline characteristics full analysis set (n=1831) age, mean (sd), y 44.6 (12.8) sex, n (%) male female 1258 (68.7) 573 (31.3) disease duration of psoriasis, mean (sd), y 18.6 (12.2) spga score, n (%) 3 4 5 (very severe) 994 (54.3) 723 (39.5) 114 (6.2) sd, standard deviation; spga, static physician’s global assessment. table 2. exposure-adjusted event rates of patients who received ≥1 dose of brodalumab through the end of the study n (r) brodalumab (all patients) (patient-years = 3228.5) (n=1790) all teaes serious aes aes leading to drug discontinuation deaths 9909 (306.9) 247 (7.7) 103 (3.2) 1 (0.1) most common aes (>250 events overall) nasopharyngitis upper respiratory tract infection arthralgia headache 620 (19.2) 499 (15.5) 295 (9.1) 288 (8.9) ae, adverse event; n, number of aes; r, exposure-adjusted event rate per 100 patient-years (n/patient-year*100); teae, treatment-emergent ae. © 2017. all rights reserved. 7810_wcdc_104 week efficacy amagine 2_m1-3.indd 1 12/11/17 5:33 pm skin september 2017 volume 1 issue 2 copyright 2017 the national society for cutaneous medicine 104 short communications early-onset basal cell carcinoma in young female endurance athletes: a report of three cases jonathan j. lee md a , emily dando ba b , kristin bibee md phd a , jaroslaw jedrych md a , jonhan ho md ms a , timothy patton do a a department of dermatology, university of pittsburgh medical center, pittsburgh, pa b university of pittsburgh school of medicine, pittsburgh, pa basal cell carcinomas (bcc) are the most prevalent cancer in the united states. while the vast majority of bccs afflict those older than 55, recent data point to a rise in the incidence of sporadic bccs in young caucasian women less than 40 years of age. 1 to date, cigarette smoking, tanning bed use, and a history of blistering sunburns have been linked to this trend. 1,2 however, the potential role of intense, intermittent outdoor ultraviolet radiation (uvr) exposure as acquired through outdoor athletics has yet to be examined. the authors recently encountered three cases of early-onset, sporadic bccs in young caucasian females between the ages of 29-34, two of whom were amateur triathletes and the third an ultramarathon runner (table 1, figure 1). this case series highlights the potential contribution of ambient uvr acquired through endurance athletics in sporadic, early-onset bcc. barton et al. (2016) recently reported the largest case-control study of early-onset bccs to date, demonstrating that they most often developed on the head and neck region of young women (mean age at diagnosis 43.3 ± 5 years) and were more likely than their later-onset counterparts to be of aggressive histological subtypes. 1 while our cases were consistent with these data by gender and anatomical location, our patients were diagnosed at an earlier age and with less aggressive histological subtypes. recent epidemiologic studies report an increased risk of early-onset bccs among those with significant sun sensitivity and a history of blistering sunburns, but these studies did not ascertain the mechanism by which this was obtained. 1,3 indeed, data addressing the contribution of endurance athletics-associated sun exposure to skin cancer risk are limited. ambros-rudolph et al. (2006) inferred an increased risk of melanoma among marathon runners based on the identification of a greater number of clinically atypical melanocytic nevi, solar lentigines, and lesions clinically suspicious for nmscs in 210 marathon runners compared to age-matched controls with more pronounced findings among those logging the greatest number of weekly miles. 4 in another study, a beachfront screening program at a texas gulf coast introduction report of three cases discussion skin september 2017 volume 1 issue 2 copyright 2017 the national society for cutaneous medicine 105 surfing event diagnosed bccs in 16% (8 of 49) of surfers with a mean age of 38 years among those affected compared to 3.2% (1 of 53) in a control population. 5 in addition to sun exposure acquired during frequent training, dosimetric studies of full distance ironman triathletes have documented substantial amounts of uv exposure during a single 8-10 hour event (mean minimal erythema dose of 8.3). 6 we hypothesize that intense, intermittent outdoor uvr exposure acquired through endurance athletic training puts athletes at increased risk of early-onset bcc and other nmscs. misconceptions regarding the extent of uvr exposure during cloud covered days or early mornings and inadequate use of sunscreen or sun protective clothing may be contributing factors. this clinical observation identifies a high-risk population who may benefit from targeted screening efforts and close clinical follow-up. in addition, continued advocacy regarding use of sun-protective measures and training-specific lifestyle modifications to reduce exposure to ambient ultraviolet radiation are warranted. case age/sex clinical history physical exam pathology endurance athletic outdoor training history sun protective measures other skin cancer risk factors 1 29/f irritated lesion on right neck for 10 months 0.7 cm erythematous, ovoid plaque with irregular, rolled borders superficial and nodular bcc ultramarathon runner: 5-6 days per week for 2-3 hour runs. participated in several outdoor ultramarathon races annually, lasting from 6-15 hours spf 30+ without reapplication, no sun protective clothing denies history of blistering sunburns or tanning bed use 2 30/f non-healing erosion on right nasal sidewall for 3 months 0.4 cm pink, pearly papule with surrounding telangiectasia and central hemorrhagic crust superficial and nodular bcc amateur triathlete: 5 days per week for 1-3 hour sessions denies use of sunscreen or sunprotective clothing denies history of blistering sunburns or tanning bed use 3 34/f irritated lesion on right cheek for 1 year 0.2 cm pink, dome-shaped papule nodular bcc amateur triathlete: 4-5 days per week for 1-2 hour sessions spf 30+ without reapplication several years tanning bed use; worked as poolside lifeguard for 6 years tables/figures table 1: clinical data from patients with early-onset basal cell carcinoma skin september 2017 volume 1 issue 2 copyright 2017 the national society for cutaneous medicine 106 conflict of interest disclosures: none. funding: none. corresponding author: jonathan j. lee, md upmc dermatology 3708 fifth avenue, suite 500.68 pittsburgh, pa 15213 leejj7@upmc.edu 925-202-7539 (us) references: 1. barton dt, zens ms, nelson hh, et al. distinct histologic subtypes and risk factors for early onset basal cell carcinoma: a population-based case control study from new hampshire. j invest dermatol. 2016;136(2):533-535. 2. boyd as, shyr y, king le, jr. basal cell carcinoma in young women: an evaluation of the association of tanning bed use and smoking. journal of the american academy of dermatology. 2002;46(5):706-709. 3. christenson lj, borrowman ta, vachon cm, et al. incidence of basal cell and squamous cell carcinomas in a population younger than 40 years. jama. 2005;294(6):681-690. 4. ambros-rudolph cm, hofmann-wellenhof r, richtig e, muller-furstner m, soyer hp, kerl h. malignant melanoma in marathon runners. archives of dermatology. 2006;142(11):14711474. 5. dozier s, wagner rf, jr., black sa, terracina j. beachfront screening for skin cancer in texas gulf coast surfers. southern medical journal. 1997;90(1):55-58. 6. moehrle m. ultraviolet exposure in the ironman triathlon. medicine and science in sports and exercise. 2001;33(8):1385-1386. figure 1: clinical images of early-onset basal cell carcinomas (bcc) identified in three young endurance athletes a) case 1: 29-year-old female ultramarathon runner with superficial/nodular bcc on right neck. b) case 2: 30-year-old female triathlete with superficial/nodular bcc on right nasal side wall. c) case 3: 34-year-old caucasian female triathlete with nodular bcc on right cheek. skin september 2017 volume 1 issue 2 copyright 2017 the national society for cutaneous medicine 83 brief articles analysis of dermatologic disorders occurring in major league baseball players alex m. glazer md a , aaron s. farberg md b , stephen donohue bs c , darrell s. rigel md ms d a university of arizona college of medicine, division of dermatology, tucson, az, b resident, icahn school of medicine at mount sinai, new york, ny, c head athletic trainer, new york yankees, bronx, ny, d clinical professor, ronald o. perelman department of dermatology, nyu school of medicine, new york, ny the most common injuries that impact athletes are skin related. 1 professional baseball players are subjected to physical and environmental stressors which may interrupt their skin’s protective barrier. 2 in addition to common dermatoses, repetitive mechanical trauma, excessive sweating, use of occlusive clothing/equipment, and communal use of equipment/facilities that is inherent to baseball activities may also abstract objective: to determine distribution of dermatologic disease among major league baseball (mlb) players and compare the distribution to that seen in the general population. design: cross sectional survey setting: data was collected via anonymous, online, randomized survey in january 2017. participants: head athletic trainers for 25 mlb teams main outcome measures: the distribution of dermatologic disease encountered by mlb athletic trainers for players versus non-player personnel. results: the 3 most commonly encountered dermatologic conditions for mlb trainers among baseball players were blisters, contact dermatitis, and nail problems including onychomycosis. in contrast, the 3 most common dermatoses seen among the non-player personnel control group were rash, tinea, and concerning skin lesion which more closely resembled the distribution of skin diseases among the general population. conclusions: mlb players experienced a different mix with a greater proportion of mechanical, infectious, and contact related skin conditions likely due to the baseball-related activities that impact on these athletes’ skin on a day-to-day basis. the prevalence of the dermatologic disorders noted in the study reinforces the importance of focused dermatologic education for trainers to enhance player care. introduction skin september 2017 volume 1 issue 2 copyright 2017 the national society for cutaneous medicine 84 predispose to sports-related skin disorders. these factors place athletes at higher risk for infection, mechanical skin injury, and exacerbation of pre-existing conditions that may inhibit their athletic performance or keep them off the field. athletic trainers (ats) play a critical role in allowing baseball players to perform at the highest possible level. they must therefore be able to identify and manage common dermatologic problems. multiple sports associated dermatoses have been described 1,2, but the distribution of skin disease specific to baseball players, to our knowledge, has not yet been investigated. the purpose of this study was to examine the most common dermatoses major league baseball (mlb) ats encounter among their team’s players and compare this disease spectrum to what is seen in their non-player personnel and the general public. online surveys were sent to the ats of all 30 mlb teams in january 2017. participants were provided with a list of 26 of the most commonly encountered skin conditions in the general us public 3 , with the order randomized for each participant, and asked to rank the conditions they most frequently encountered for mlb players and non-player personnel. additionally, participants were surveyed about team access to a dermatologist. results were analyzed and the groups were compared. 25 of 30 (83%) mlb ats responded and completed all of the survey questions. the most commonly encountered dermatoses among mlb players versus non-player personnel controls are summarized in table 1. all responding ats reported having access to a primary team dermatologist. the distribution of skin diseases that mlb ats encountered among non-player personnel closely resembled what has been noted in the general us population. 3 however, mlb players experienced a different mix with a greater proportion of mechanical, infectious, and contact related skin conditions likely due to the baseballrelated activities that impact on these athletes’ skin on a day-to-day basis. the mlb has partnered with the american academy of dermatology since 1999 for the play sun smart program to promote skin cancer awareness. dermatologists have been active in educating team medical staffs about issues related to sun protection and skin cancer. based upon the results of this study, there may be the potential to expand this education to non-cancer dermatologic disorders that the ats regularly encounter. a strong understanding of these common mechanical and infectious dermatoses is also important and the team dermatologist may be the best source to provide this knowledge. as the understanding and treatment methods for these conditions evolve, 4,5 it is important that ats work collaboratively with dermatologists to stay up to date about the dermatoses that they most commonly encounter. education that enhances the identification and efficient implementation of proper treatment has the potential to minimize the impact of skin disease on mlb player performance. methods results discussion skin september 2017 volume 1 issue 2 copyright 2017 the national society for cutaneous medicine 85 conflict of interest disclosures: none. funding: none. acknowledgements: we thank the major league baseball athletic trainers for their response and participation in this survey. corresponding author: alex m. glazer, md department of dermatology, university of arizona po box 245024 1515 n. campbell avenue tucson, az 85724-5024 email: alexglazer@gmail.com phone: 212-685-3252 references: 1. adams bb. dermatologic disorders of the athlete. sports med. 2002;32(5):309-321. 2. pharis db, teller c, wolf je. cutaneous manifestations of sports participation. j am acad dermatol. 1997;36:448-459. 3. wilmer en, gustafson cj, ahn cs, et al. most common dermatologic conditions encountered by dermatologists and nondermatologists. cutis. 2014;94(6):285292. 4. mcnamara ar, ensell s, farley td. hand blisters in major league baseball pitchers: current concepts and management. am j orthop. 2016;45(3)134-136. 5. mitchell jj, jackson jm, anwar a, et al. bacterial sport-related skin and soft-tissue infections (sstis): an ongoing problem among a diverse range of athletes. jbjs reviews. 2017;5(1): e4. published online: https://doi.org/10.2106/jbjs.rvw.16 .00006 most commonly encountered skin conditions rank mlb players non-player personnel 1 blisters rash 2 contact dermatitis tinea (groin, body, foot) 3 onychomycosis or other nail problem concerning skin lesion (mole/skin cancer) 4 ingrown hair/folliculitis onychomycosis or other nail problem 5 tinea (groin, body or foot) folliculitis or ingrown hair 6 rash contact dermatitis 7 callus sunburn 8 ecchymosis/contusion cyst 9 other bacterial skin infection (cellulitis/abcess) atopic dermatitis 10 verruca vulgaris verruca vulgaris table 1: the most common dermatoses among mlb players and non-player personnel mailto:alexglazer@gmail.com https://doi.org/10.2106/jbjs.rvw.16.00006 https://doi.org/10.2106/jbjs.rvw.16.00006 skin january 2019 volume 3 issue 1 copyright 2018 the national society for cutaneous medicine 114 compelling comments adrenal insufficiency and its presidential touch christopher dallo, bs1, benjamin falck, bs1 1university of texas medical branch school of medicine, galveston, tx tall, tan, and handsome are three words that often come to mind when we describe the 35th president of the united states, john f. kennedy. kennedy’s ascendancy to presidency over richard nixon was historic as he won the national popular vote by a margin of over 118, 000 votes. the series of candidate debates held during that election cycle, dubbed the “great debates”, were similarly historic as they represent the first televised presidential debates in the nation’s history and played a critical role in kennedy’s success. on september 26, 1960, the two candidates squared off in the cbs news station in downtown chicago.1 before air, both candidates declined any touch-ups from the cbs makeup artists. with the cameras live, the whole world was able to contrast kennedy’s enviable skin against nixon’s uninviting wan complexion and shabby stubble. kennedy’s glowing skin may have been attributed to primary adrenal insufficiency – an autoimmune destruction of the adrenal gland that results in decreased cortisol levels. this relieves inhibition at the hypothalamus and indirectly stimulates the pituitary gland to increase the production of proopiomelanocortin (pomc), a precursor of adrenocorticotropic hormone and melanocyte-stimulating hormone (msh). the inadvertent increase of msh promotes melanin production, which leads to skin hyperpigmentation. this might justify kennedy’s seductive tan, although sources later alleged that kennedy was graced with touch-ups from his own team before entering the spotlight.1 jfk’s brother, robert kennedy, also came to his defense when he publicly stated during the campaign trail that his brother never had addison’s disease, and had only suffered “some mild adrenal insufficiency” during the post-war period, which had since “corrected over the years.”2 polls reported that more than half of the voters in the election were influenced by the great debates.1 jfk repeatedly denied having any form of adrenal disease throughout his presidential run, and boldly claimed himself as “the healthiest candidate for president in the country.”3 after his death however, his family members were reluctant to have pathologists examine his abdominal cavity during the autopsy.3 in 1992, nearly 29 years after his assassination, a pathologist from his post-mortem examination finally broke silence and confirmed that john f. kennedy’s adrenal glands were not even visible.4 conflict of interest disclosures: none. funding: none. skin january 2019 volume 3 issue 1 copyright 2018 the national society for cutaneous medicine 115 corresponding author: christopher dallo, bs the university of texas medical branch galveston, tx chdallo@utmb.edu references: 1. altman, l. k. (1992, october 06). the doctor's world; disturbing issue of kennedy's secret illness. retrieved march 29, 2018, from https://www.nytimes.com/1992/10/0 6/health/the-doctor-s-worlddisturbing-issue-of-kennedy-s-secretillness.html. 2. brown, d. (1992, october 6). jfk’s addison’s disease. the washington post. history.com staff. (2010). the kennedy-nixon debates [television broadcast]. in history. new york city, new york: a&e networks. 3. bumgarner, j. r. (1994). the health of the presidents: the 41 united states presidents through 1993 from a physician's point of view. jefferson, nc: mcfarland & company. https://www.nytimes.com/1992/10/06/health/the-doctor-s-world-disturbing-issue-of-kennedy-s-secret-illness.html https://www.nytimes.com/1992/10/06/health/the-doctor-s-world-disturbing-issue-of-kennedy-s-secret-illness.html https://www.nytimes.com/1992/10/06/health/the-doctor-s-world-disturbing-issue-of-kennedy-s-secret-illness.html https://www.nytimes.com/1992/10/06/health/the-doctor-s-world-disturbing-issue-of-kennedy-s-secret-illness.html skin september 2017 volume 1 issue 2 copyright 2017 the national society for cutaneous medicine 95 brief articles sarcoidosis developing during secukinumab therapy: case report timothy nyckowski a , roger ceilley md a,b , joshua wilson md a a dermatology p.c., west des moines, iowa b university of iowa carver college of medicine, department of dermatology, iowa city, iowa sarcoidosis is a systemic granulomatous disease and skin is the most common organ affected after the lungs. 1 sarcoidosis is a diagnosis of exclusion, supported by clinical, radiologic, and histologic findings consistent with the disease. 2 non-caseating epitheloid granulomas without a known cause warrants consideration of sarcoidosis in the differential diagnosis. 1 cutaneous sarcoidosis has been associated with several chemotherapeutic medications, biologic agents, and injection sites. 3 among the many possible associations, there have been no reported associations with il-17 inhibitors in the literature at this time. recent studies have made advances in defining the role of il-17 in sarcoidosis. 2,4 il-17 is involved in numerous other autoimmune processes, including ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis. 2 though some studies have suggested that il-17 inhibition may be a mechanism of treatment for sarcoidosis, abstract introduction: sarcoidosis is a systemic granulomatous inflammatory disease with an unknown etiology and complex pathogenesis. existing literature supports the relationship of new-onset sarcoidosis with the use of a several biologic agents. since the skin is the second most commonly involved organ in sarcoidosis and often precedes systemic involvement, dermatologists must be able to recognize its non-specific clinical presentation. case report: we present a 45 year old female with psoriatic arthritis who developed biopsy proven cutaneous sarcoidal granulomas with pulmonary involvement shortly after initiating secukinumab for treatment of psoriatic arthritis. despite discontinuation of secukinumab, the sarcoidosis has persisted. discussion: this is the first case report of secukinumab or any il-17 inhibitor related sarcoidosis that we are aware of in the literature. dermatologists should be aware of this as a possible side effect of secukinumab use. as the research on the role of il-17 in the pathogenesis of sarcoidosis continues to develop, the implications of this side effect of il-17 inhibition may have important future implications. introduction skin september 2017 volume 1 issue 2 copyright 2017 the national society for cutaneous medicine 96 other studies have demonstrated that il-17 has a protective effect from the development of sarcoidosis. a 45 year old female was referred to our dermatology office by her rheumatologist who was treating her for psoriatic arthritis with secukinumab. around the same time secukinumab was initiated, she developed firm, tender, cord-like and linear subdermal nodules involving mainly the upper extremities and right ankle. medical history revealed she had a history of iv drug use and hepatitis c, completely treated with ledipasvir/sofosbuvir. excisional biopsy of the left forearm was performed to the depth of the subcutaneous tissue and the specimen was sent to pathology for diagnostic purposes. the initial differential diagnosis included interstitial granulomatous dermatitis of the forearms, deep granuloma annulare, sarcoidosis, and calcinosis cutis. the histopathologic report revealed a diagnosis of superficial and deep non-caseating granulomatous inflammation consistent with sarcoidosis (figure 1, figure 2). when the patient returned for follow up in 14 days to discuss the pathology report, we counseled her on her diagnosis of sarcoidosis and she decided to discontinue secukinumab treatment, with her last dose being 12 days prior. she reported partial improvement in the bilateral antecubital fossa, but the cutaneous manifestations persisted. chest x-ray revealed mild bilateral hilar prominence reflecting lymphadenopathy and a mild diffuse bilateral interstitial prominence suggestive of sarcoidosis, viral process, or reactive airway disease. case report figure 1: low-power magnification displays noncaseating granulomatous inflammation figure 2: high-power magnification displays superficial and deep dermal and subcutaneous granulomatous inflammation comprised of epithelioid histiocytes and giant cells in tight-formed granulomas skin september 2017 volume 1 issue 2 copyright 2017 the national society for cutaneous medicine 97 sarcoidosis is an inflammatory disease characterized by non-caseating granulomas with mononuclear cell infiltration and localized injury. the skin may be the initial site involved in 30% of patients. 3 cutaneous sarcoidosis has a variable presentation, and specific morphologies of some cutaneous lesions have prognostic significance. 3 the complex pathogenesis of sarcoidosis is highlighted by the many biologic drugs implicated with causing this disease. sarcoidosis is associated with the use of: ipilimumab, pembrolizumab, vemurafenib, tnf-α inhibitors, interferon, ustekinumab, and anakinra. 1, 3,5-8 the relationship of sarcoidosis with tnf-α inhibitors is a dichotomous one, as tnf-α inhibitors both cause and treat sarcoidosis. 1, 8, 9 some of these studies have suggested monitoring new agents such as il-17 and il-23 inhibitors for similar paradoxical adverse events. 9 to date, there are no previously reported cases of sarcoidosis in the pubmed database related to the initiation of secukinumab. secukinumab is a fully human, monoclonal antibody to il-17a. the use of secukinumab leads to a decrease in il-17a levels, dermal inflammatory infiltrate, and epidermal thickening. 10 secukinumab is approved by the food and drug administration (fda) for use in moderate to severe plaque psoriasis, psoriatic arthritis, and ankylosing spondylitis. 10 common side effects are nasopharyngitis, upper respiratory infection, headache, and diarrhea. 10 il-17 levels are elevated in the tissues, serum, and bronchoalveolar lavage (bal) samples of patients affected with sarcoidosis. 2 evidence for the involvement of il-17a in the pathogenesis of sarcoidosis includes: (1) increased circulating il-17a+ memory t cells, (2) increased il-17a producing cells (il-17a/ifn-γ and il-17a/il4 cells) in bal samples, (3) increased t cells producing il-17a in the lungs of sarcoidosis patients, and (4) differential distribution of il-17a producing t cells in local granulomas. 2 thus, some authors suggest il-17 inhibition may be a treatment for sarcoidosis. 2 il-17 producing cells are present in the periphery of granulomas localized in the peri-lymphocytic region as well as inside granulomas. 4,11 il-17 is required to clear primary infections and establish effective memory cell responses. 2 granulomatous inflammation occurs when macrophages are unable to eradicate an antigen. historical knowledge about the complexity of immune-mediated diseases such as sarcoidosis demonstrates why it could be possible to induce sarcoidosis with il-17 inhibition. sarcoidosis has been described as an immune paradox because peripheral anergy occurs in the setting of enhanced inflammation at disease sites. 2 il-17 expressed in sarcoidosis has both a proinflammatory role and protective role in the development of sarcoidosis. 11,12 sarcoidosis patients have a subset of t cells that are able to produce il-17 and ifn-γ simultaneously, known as il-17/ifn-γ t cells. 11 these hybrid th1/th17 cells may be more pathogenic than conventional th17 cells. 11 furthermore, the majority of th17 cells can produce ifn-γ. 11 given these data, il-17 inhibition by secukinumab could lead to an imbalance of il-17 production that would favor granulomatous if-γ production. furthermore, the plasticity of t cell populations has been demonstrated in animal studies, as th17 cells can take on a th1 phenotype. 11 discussion skin september 2017 volume 1 issue 2 copyright 2017 the national society for cutaneous medicine 98 in patients suffering from sarcoidosis, increased levels of il-17 found in the bal fluid is correlated with a better disease prognosis. 11 cautious optimism regarding systemic suppression of il-17 is encouraged, as the complexity of the immunologic system can reveal unintended consequences from cytokine suppression. 12 there is a tenuous balance between cytokine signaling processes in immune-mediated diseases such as psoriasis. tnf-α, ifn, and il-23/th17 axis cytokines are linked together in such a way that targeting one of these cytokines can cause immunologic consequences on the other two. 9 with the advent of this case report, biologic drug-induced sarcoidosis has been demonstrated by targeting each of these same 3 cytokines. continuing studies demonstrating the mechanisms of sarcoidosis pathogenesis are needed. il-17 is increasingly recognized as playing a fundamental role in the pathogenesis of sarcoidosis. while studies have demonstrated increased il-17 levels in patients with sarcoidosis, we report a paradoxical case where an il-17 inhibitor was related to the onset of sarcoidosis. while there is much more that can be said about the relationship of il-17 and sarcoidosis, this report will fortify future exploration regarding the dichotomous relationship of il-17 with sarcoidosis. conflict of interest disclosures: none. funding: none. corresponding author: timothy nyckowski 6000 university avenue, #450 west des moines, ia 50266 847-791-4324 timothynyckowski@gmail.com references: 1. amber kt, bloom r, mrowietz u, hertl m. tnf-α: a treatment target or cause of sarcoidosis? j eur acad dermatol venereol. 2015 nov;29(11):2104-11. 2. mortaz e, rezayat f, amani d, kiani a, garssen j, adcock im, velayati a. the roles of t helper 1, t helper 17 and regulatory t cells in the pathogenesis of sarcoidosis. iran j allergy asthma immunol. 2016 aug;15(4):334-339. 3. noe mh, rosenbach m. cutaneous sarcoidosis. curr opin pulm med. 2017 jun 8. 4. sakthivel p, bruder d. mechanism of granuloma formation in sarcoidosis. curr opin hematol. 2017 jan;24(1):59-65. 5. waltschew a. [cutaneous sarcoidosis after treatment with interferon for hepatitis c: a not entirely rare but often overlooked reaction]. pathologe. 2016 mar;37(2):184-6. 6. powell jb, matthews p, rattehalli r, woodhead f, perkins p, powell g, szczecinska w, gach je. acute systemic sarcoidosis complicating ustekinumab therapy for chronic plaque psoriasis. br j dermatol. 2015 mar;172(3):834-6. 7. sacre k, pasqualoni e, descamps v, choudat l, debray mp, papo t. sarcoid-like granulomatosis in a patient treated by interleukin-1 receptor antagonist for tnfreceptor-associated periodic syndrome. rheumatology (oxford). 2013 jul;52(7):1338-40. 8. daïen ci, monnier a, claudepierre p, constantin a, eschard jp, houvenagel e, samimi m, pavy s, pertuiset e, toussirot e, combe b, morel j; club rhumatismes et inflammation (cri). sarcoid-like granulomatosis in patients treated with tumor necrosis factor blockers: 10 cases. rheumatology (oxford). 2009 aug;48(8):8836. conclusion skin september 2017 volume 1 issue 2 copyright 2017 the national society for cutaneous medicine 99 9. toussirot é, aubin f. paradoxical reactions under tnf-α blocking agents and other biological agents given for chronic immunemediated diseases: an analytical and comprehensive overview. rmd open. 2016;2(2):e000239. 10. armstrong aw, papp k, kircik l. secukinumab: review of clinical evidence from the pivotal studies erasure, fixture, and clear. j clin aesthet dermatol. 2016 jun;9(6 suppl 1):s7-s12. 11. ostadkarampour m, eklund a, moller d, glader p, olgart höglund c, lindén a, grunewald j, wahlström j. higher levels of interleukin il-17 and antigen-specific il-17 responses in pulmonary sarcoidosis patients with löfgren's syndrome. clin exp immunol. 2014 nov;178(2):342-52. 12. tan hl, rosenthal m. il-17 in lung disease: friend or foe? thorax. 2013 aug;68(8):78890. incidence, characteristics, and management of alpelisib-associated rash in patients with advanced breast cancer anisha b. patel, md1,a; lucia seminario-vidal, md, phd2  1university of texas md anderson cancer center, houston, tx; 2h. lee moffitt cancer center, tampa, fl authors contributed equally to this work apresenting author presented at: 2020 fall clinical dermatology conference. october 29-november 1, 2020. las vegas, nv. synopsis • hormone receptor-positive (hr+), human epidermal growth factor receptor-2–negative (her2–) breast cancer is the most common subtype of advanced breast cancer (abc).1 • ~40% of patients with hr+, her2– breast cancer have mutations in the pik3ca gene, which encodes the α subunit of phosphatidylinositol-3-kinase (pi3k).2-4 – pik3ca mutations have been associated with the development of resistance to endocrine therapy, and are a negative prognostic factor in abc.4,5 • alpelisib is an α-selective pi3k inhibitor approved in combination with fulvestrant for the treatment of patients with hr+, her2– abc with mutations in the pik3ca gene who progressed on or after endocrine therapy.6 – u.s. food & drug administration (fda) approval of this combination was based on improved efficacy data compared with placebo plus fulvestrant, and a manageable safety profile reported in the phase iii solar-1 trial (nct02437318).7 • cutaneous toxicities, particularly the development of rash, are a class effect of pi3k pathway inhibitors and have been reported in up to 54% of patients treated with alpelisib.7-9 objective • the objective of this poster is to provide dermatologists with specific guidance on the management of alpelisib-associated dermatologic adverse events. methods • this review of alpelisib-associated rash includes safety data from the solar-1 trial, the bylieve study, and a single-center retrospective study. – solar-1 evaluated alpelisib (300 mg qd) + fulvestrant (500 mg, every 28 days and once on day 15) or placebo + fulvestrant (equal dosing) in women or men with hr+, her2− abc who had progressed on or after prior aromatase inhibitor (n=572).7 – bylieve (nct03056755), is an ongoing phase ii study evaluating alpelisib (300 mg qd) + fulvestrant (500 mg, every 28 days and once on day 15) or letrozole (2.5 mg qd) in women of any menopausal status and men with hr+, her2− abc and confirmed pik3ca-mutant status who had progressed on or after prior treatments.10 • results from cohort a (n=127; cohort of patients previously treated with cyclin-dependent kinase [cdk]4/6 inhibitors) have recently been reported and are included here. – a single-center retrospective study evaluated data from 4 randomized trials and postapproval treatment records involving abc patients who received alpelisib-based treatments (most frequently combined with endocrine therapy; n=102), with the purpose of characterizing alpelisib-associated cutaneous toxicities and describing management strategies.11 • alpelisib prescribing information and other available literature are also included. results incidence of alpelisib-associated rash • clinical trials have reported an incidence of any-grade rash (by single preferred term) ranging from 28% to 36% (grade ≥3 = 9%-10%) in alpelisib-treated patients.7,10 – rash led to treatment discontinuation in 3% to 4% of these patients. – no grade 4 rash was reported in solar-1 or in the retrospective study.7,9,11 characteristics of rash • in clinical studies, the median time to rash onset was approximately 2 weeks after starting alpelisib treatment.9,11 • in the retrospective study, median duration of rash was 7 days.11 – in solar-1, the median time to improvement by at least 1 grade in patients with grade ≥3 rash was 11 days.9 • rash is more frequently localized in the trunk (including chest, abdomen, and back) and extremities; rash on face and scalp is less common.11 • rash events can be asymptomatic, or present symptoms such as burning pain or pruritus (more common in grade 3 rash).11 36 73 53 70 53 70 41 15 26 20 27 14 23 12 21 10 20 16 0 10 20 30 40 50 60 70 80 no prophylaxis (n=198) prophylaxis (n=86) no prophylaxis (n=117) prophylaxis (n=10) no prophylaxis (n=59) prophylaxis (n=43) no rash grade 1/2 rash grade 3/4 rash bylieve p at ie n ts , % retrospective studyasolar-1a ctcae grading alpelisib dosing supporting medication alpelisib rechallenge grade 1 <10% bsa with active skin toxicity. no alpelisib dose adjustment required. initiate class i-iii topical corticosteroids (triamcinolone, betamethasone, clobetasol, or fluocinonide). • if presenting with pruritus or burning sensation, add antihistamines in the morning (nonsedating: cetirizine/loratadine) and at night (sedating: hydroxyzine or diphenhydramine). • if presenting with acneiform rash, consider other causative agents (oral contraceptives, antiandrogen medications, dehydroepiandrosterone, etc); avoid diphenhydramine. alpelisib may be resumed at the same dose once rash resolves to grade ≤1, or at a reduced dose at second occurrence. a graded rechallenge with alpelisib may also be considered while maintaining antihistamine treatment and tapering systemic steroids. interrupt alpelisib until improved to grade ≤1. follow grade 1/2 supporting medication, and initiate systemic corticosteroidsb (prednisonec, 10-14 days with taper). permanently discontinue alpelisib. grade 2 10%-30% bsa with active skin toxicity. grade 3 30% bsa with active skin toxicity. grade 4 life-threatening; any % bsa with extensive superinfection and iv antibiotics indicated. conclusions • rash is a frequently observed alpelisib-associated adverse event that can be managed with medication, such as antihistamines and corticosteroids, and alpelisib dose adjustments and interruptions. – rash leading to alpelisib treatment discontinuation did not occur frequently in clinical studies and most patients were able to resume anticancer treatment upon rash resolution. • preventive strategies, such as administration of prophylactic medication, patient education, early detection of symptoms, and prompt treatment, may help minimize the onset and severity of alpelisib-associated rash. • severe cutaneous reactions (sjs, em, dress, and ten) are not common in patients treated with alpelisib; if suspected, alpelisib should be interrupted, and permanently discontinued if diagnosis is confirmed. references 1. blows fm, et al. plos med. 2010;7(5):e1000279. 2. cancer genome atlas network. nature. 2012;490(7418):61-70. 3. mollon l, et al. aacr 2018. poster 1207. 4. mosele f, et al. ann oncol. 2020;31(3):377-386. 5. sobhani n, et al. j cell biochem. 2018;119(6):4287-4292. 6. piqray [prescribing information]. east hanover, nj: novartis pharmaceuticals corp; 2019. 7. andré f, et al. n engl j med. 2019;380(20):1929-1940. 8. schindler k, et al. j clin oncol. 2014;32:e20639. 9. rugo hs, et al. ann oncol. 2020;31(8):1001-1010. 10. rugo hs, et al. asco 2020. abstract 1006 (oral). 11. wang dg, et al. breast cancer res treat. 2020;183(1):227-237. 12. u.s. department of health and human services, nih, national cancer institute. common terminology criteria for adverse events v4.0 (ctcae). 13. u.s. department of health and human services, nih, national cancer institute. common terminology criteria for adverse events v4.03 (ctcae). 14. nunnery se, mayer ia. ann oncol. 2019;30(suppl 10):x21-x26. 15. chia s, et al. curr oncol. 2015;22(1):33-48. 16. balagula y, et al. cancer. 2012;118(20):5078-5083. 17. bc cancer. provincial health services authority. http://www.bccancer.bc.ca/. accessed august 31, 2020. 18. tan au, et al. int j womens dermatol. 2017;4(2):56-71. 19. tamez-perez hl, et al. world j diabetes. 2015;6(8):1073-1081. acknowledgments medical editorial assistance was provided by casandra m. monzon, phd, healthcare consultancy group, llc, and was funded by novartis pharmaceuticals corporation. prevention of alpelisib-associated rash • administering prophylactic medication to patients receiving alpelisib before the onset of rash has been shown to reduce the incidence and severity of this adverse event (figure 1).9 -11 figure 1. occurrence of rash in patients who received prophylaxis and those who did not • strategies that both health care professionals (hcps) and patients can adopt to prevent the onset of alpelisib-associated rash are described in figure 2.9 -11 severe cutaneous reactions • life-threatening skin toxicities, such as stevens-johnson syndrome (sjs), erythema multiforme (em), drug reaction with eosinophilia and systemic symptoms (dress), and toxic epidermal necrolysis (ten) are not common.6,11 – patients with a history of severe cutaneous reactions should not start alpelisib treatment.6 – symptoms may include a prodrome of fever, flu-like symptoms, mucosal lesions, or progressive skin rash.6 – alpelisib should be interrupted if severe cutaneous reactions are suspected, and permanently discontinued if diagnosis is confirmed or grade 4 rash occurs.6 management of alpelisib-associated rash • alpelisib-associated rash is generally reversible with adequate co-medication and, if needed, alpelisib dose adjustments/interruption (mostly in patients experiencing grade 3 rash; figure 3).7,11 – retrospective data showed that upon improvement to grade ≤1 rash, 12 of 16 patients (75%) who interrupted treatment were able to resume alpelisib and did not experience rash recurrence (9 of those patients were rechallenged with the initial alpelisib dose); 4 patients (25%) experienced rash recurrence within 24 hours of alpelisib rechallenge and required permanent alpelisib discontinuation.11 • active management of alpelisib-associated rash may help limit dose adjustments and prevent treatment interruptions to achieve better therapeutic efficacy.9,11 • management strategies include – early identification and intervention – patient education – clear guidance on preventive treatment – hcp training on supportive medications and dose adjustment protocols • in solar-1, more detailed management guidelines introduced after a protocol amendment resulted in a decrease in incidence of grade 3 rash.9 figure 3. management of alpelisib-associated rash based on severity6,7,11,17,18,a • the vast majority of patients who develop alpelisib-associated rash present with maculopapular (morbilliform) rash; acneiform rash can also be observed. characteristics of these 2 rash types are presented in table 1.11 • retrospective data from 2 patients who experienced alpelisib-associated rash showed histology consistent with a hypersensitivity reaction.11 • laboratory assessment data showed that patients who developed rash had an increase in blood eosinophils after 2 weeks of alpelisib treatment compared with baseline (2.7% vs 4.4%, p<0.05); a trend toward elevated alt was also observed.11 – no differences in lymphocyte, neutrophil, or monocyte counts were reported between patients who developed rash and those who did not. this presentation is the intellectual property of the author/presenter. contact them at apatel11@mdanderson.org for permission to reprint and/or distribute. copies of this poster obtained through quick response (qr) code are for personal use only and may not be reproduced without permission of the authors. text: q1ad94 to: 8nova (86682) us only + 18324604729 north, central, and south americas; caribbean; china +447860024038 uk, europe, and russia +46737494608 sweden and europe visit the web at: http://novartis.medicalcongressposters.com/ default.aspx?doc=1ad94 scan this qr code ano grade 4 rash was reported in solar-1 or in the retrospective study. aevaluation by a dermatologist familiar with these toxicities is recommended. bsystemic corticosteroids may worsen alpelisib-associated hyperglycemia. caution should be exercised.19 cmethylprednisolone or prednisolone are preferred over prednisone for patients with liver disease. bsa, body surface area; ctcae, common terminology criteria for adverse events; iv, intravenous. table 1. characteristics of alpelisib-associated rash rash type relative incidence11 possible symptoms11-13 clinical features11-15 histopathological characterization11,16 maculopapular (morbilliform) 26 of 29 patients in the alpelisib retrospective study (90%) experienced maculopapular rash; more common in patients receiving alpelisib plus hormone therapy • pruritic • burning sensation • tightness • presence of macules and papules • centripetal distribution; mostly localized on upper trunk and extremities • superficial perivascular dermatitis with focal or mild interface change or folliculocentric spongiosis • may present with lymphocytic infiltration acneiform 3 of 29 patients in the alpelisib retrospective study (10%) experienced acneiform rash; more common in patients with her2+ bc receiving alpelisib plus trastuzumab and anti-her3 ab • generally asymptomatic; however, pruritus and tenderness may occur • presence of papules or pustules • wide distribution; frequently located on face, scalp, upper chest, and back • presence of open comedones has been observed with everolimus, which inhibits another node of the pi3k pathway (mtor) • histopathology for alpelisib-associated acneiform rash not reported • patients treated with everolimus have presented with eczematous histology, interface dermatitis, and spongiosis ab, antibody; bc, breast cancer; her, human epidermal growth factor receptor; mtor, mammalian target of rapamycin; pi3k, phosphatidylinositol-4,5-bisphosphate 3-kinase. figure 2. rash prevention strategies hcps • consider prescribing prophylactic nonsedating antihistamines (10 mg/day cetirizine or loratadine) to patients starting alpelisib during the first 8 weeks of therapy. • educate patients on the signs and symptoms of alpelisib-associated rash for early-reporting and prompt management. patients • maintain proper skin hydration. • avoid sun exposure and irritant skin products to prevent worsening of rash, dryness, and itching. skin may 2019 volume 3 issue 3 copyright 2018 the national society for cutaneous medicine 215 brief articles fibroelastolytic papulosis in a middle-age female: presentation and review of treatment carl barrick, do,1 an guo michael chin, do, mph, ms2 veronica rutt, do1, nektarios lountzis, md3, cynthia bartis, md3 1lehigh valley health network, allentown, pa 2philadelphia college of osteopathic medicine, philadelphia, pa 3lehigh valley health network and advanced dermatology associates, ltd, allentown, pa fibroelastolytic papulosis (fep) is a rare acquired, non-systemic, skin disease that presents as white-ivory to yellow papules and plaques commonly occurring on the neck (1). in 1989 shimizu et al. reported an isolated asymptomatic white fibrous plaque with histopathological changes of fibrosis in the papillary and upper reticular dermis which was coined as white fibrous papulosis of the neck (wfpn) (2). in 1992 rongioletti and rebora reported a similar skin lesion identifying it as pseudoxanthoma elasticumlike papillary dermal elastolysis (pxe-pde), which, unlike pxe, does not have systemic associations (3). balus et al. first proposed the name “fibroelastolytic papulosis of the neck" (fepn) in 1997 to encompass both wfpn and pxe-pde, since they believed these skin disorders were a continuum of a single entity (4,5). despite the name, fepn can occur in other locations besides the neck, thus jagdeo et al. recommended changing the name to solely “fibroelastolytic papulosis (fep)” in 2004 (6). clinically, fep presents as multiple (20-100), 4-6 mm firm papules often coalescing into a fibroelastolytic papulosis (fep) is a rare, benign, acquired cutaneous disease with a histopathology that shows variable fibrosis and elastolysis of the papillary dermis. fep clinically presents as white-ivory to yellow papules and plaques commonly occurring on the neck. there are no widely accepted treatment guidelines and several management options will be discussed. we present a 62-year-old female with an isolated ivory, cobblestoned plaque with open comedones on the left shoulder since childhood. the histopathology confirmed the diagnosis of fep. the patient had been previously treated with topical clindamycin, salicylic acid, tretinoin, and tazarotene without success. this case demonstrates the importance of recognizing fep, as clinical presentations can vary. fep can be distressing to patients, and it is important to explore additional treatment options. treatment options including topical retinoids and ablative lasers have been reported, but with limited and inconsistent success. however, due to the rarity of the disease there is currently no standard of care for the treatment of fep and additional successful treatment options are needed. abstract introduction skin may 2019 volume 3 issue 3 copyright 2018 the national society for cutaneous medicine 216 cobblestone plaque. they range in color from flesh colored to white-ivory to yellow. the papules and plaques are generally asymptomatic, but inflamed folliculitis-like areas and pruritus can occur. fep is found on the posterior and lateral aspects of the neck with extension to surrounding areas. the histopathology of fep presents as loss or alteration of elastic fibers and fibrosis of the papillary and upper reticular dermis(7). pxe and pxe-pde will reveal calcified elastic fibers(3). the pathogenesis of fep has yet to be elucidated, but it is commonly theorized that it is related to an intrinsic photo-aging process. fep most often occurs in patients over the age of 40 with a predilection for females of european ancestry (7). the lesions of fep are benign, but can often progress and be cosmetically distressing to patients. there are no standard fep treatments established at this time due to its rarity. we report an interesting case of fep in a 62-year-old caucasian female and explore treatment options. a 62-year-old female patient with a past medical history significant for hypothyroidism and hyperparathyroidism presented with a large lesion on her left shoulder since childhood. the patient described it as generally asymptomatic but reported intermittent pimple-like lesions within the plaque that developed later in life. physical exam revealed multiple 2-4 mm flesh-colored to ivory papules coalescing into a large cobblestone, well-defined plaque with inflammatory papules and open comedones on the left shoulder extending on to the left upper back and proximal left upper extremity (figure 1). figure 1: clinical image demonstrating multiple 24mm fleshed colored to ivory papules coalescing into a large cobblestone-pattern plaque with dilated comedonal openings on the left shoulder and proximal left arm. the histopathology revealed intradermal proliferation of variably sized tubular structures lined by a multi-cell layered epithelium and filled with amorphous basophilic material. distinct small areas of superficial dermal collagen thickening with some of the collagen bundles becoming hyalinized, thickened and amorphous were present (figures 2, 3). focal patchy inflammation was noted within portions of the dermis surrounding the hyalinized nodules. considering the clinical presentation and histopathological correlation, the diagnosis of fep was made. due to the acneiform nature of the lesions within the plaque the following treatments were attempted; topical clindamycin 1% lotion, salicylic acid wash, benzoyl peroxide 5% wash, tretinoin 0.5% cream, and tazarotene 0.1% without considerable improvement. patient refused all additional treatment including fractionated carbon dioxide laser treatments. case report skin may 2019 volume 3 issue 3 copyright 2018 the national society for cutaneous medicine 217 figure 2: hematoxylin and eosin (4x) slide from a punch biopsy of left mid superior scapula demonstrating superficial dermal collagen thickening, some of which are sharply defined, with some of the collagen bundles becoming hyalinized, thickened and amorphous. some focal patchy inflammation is noted within portions of the dermis surrounding the hyalinized nodules as well. figure 3: hematoxylin and eosin (20x) slide from a punch biopsy of left mid superior scapula demonstrating hyalinized, thickened and amorphous superficial dermal collagen. some focal patchy inflammation is noted within portions of the dermis surrounding the hyalinized nodules as well. fep is a rare acquired skin disorder that shows elastolysis of the papillary dermis. fep encompasses wfpn and pxe-pde due to considerable overlap in clinical presentations and histopathology. the pathogenesis of fep is not well understood, but may be secondary to intrinsic and photoaging processes (8). fep is a non-life threatening skin disease, nevertheless it can be distressing for many patients due to cosmesis. in the case reported the patient experienced discomfort due to inflammatory lesions. there are currently no standard treatment guidelines established for fep. considering the benign nature of fep, treatment is not necessary. however, many patients are cosmetically concerned with fep and seek treatment. tretinoin may be a viable non-invasive, well-tolerated option for patients with fep, but results are inconsistent and often not curative. one case report documented the use of topical tretinoin 0.05% cream twice a day with significant improvement after five weeks (8). similarly, another case of fep treated with topical tretinoin 0.1% gel improved after three months and revealed complete resolution in one year (9). in contrast, a case reported by lueangarum, et al., did not improve with tretinoin in their patient (10).the patient we presented also did not show improvement with tretinoin. the exact mechanism by which tretinoin acts on fep is unknown (8). moreover, two case reports, one by chong et al., and the other by ho et al., documented successful treatment of fep with fractionated carbon dioxide (co2) laser (smartxide deka dot® laser)(1) (11), with improvement after three successive laser treatments and complete resolution within a year. another case report highlighted the successful treatment of fep utilizing a nonablative fractional photo thermolysis laser (fractionated 1550-erbium glass laser) (10). based on these findings, it appears that laser treatment may be a viable treatment option for fep. surgical excision can also be discussion skin may 2019 volume 3 issue 3 copyright 2018 the national society for cutaneous medicine 218 considered in a small well-defined lesion of fep (10). fibroelastolytic papulosis (fep) is a rare benign skin disorder that can be distressing to patients, and has no established treatment guidelines to date. our case demonstrates a unique clinical presentation and the need to explore additional treatment options for fep. there have been few successful fep treatments documented but ablative lasers appear promising. despite inconsistent results with topical retinoids, this modality could also still be considered as a conservative first line approach to therapy. no single treatment has been thoroughly studied for its efficacy in fep, therefore treating each case on an individual basis with patient consideration is recommended. conflict of interest disclosures: none. funding: none. corresponding author: carl barrick, do lehigh valley health network allentown, pa barriccj@gmail.com references: 1. chong s, woodley d, kim g, shim e. treatment of fibroelastolytic papulosis with fractionated carbon dioxide laser. j cosmet laser ther. 2015;17(2):90-92. 2. shimizu h, kimura s, harada t, nishikawa t, white fibrous papulosis of the neck: a new clinicopathologic entity? j am acad dermatol. 1989;20:1073-1077. 3. rongioletti f, rebora a. pseudoxanthoma elasticum-like papillary dermal elastolysis. j am acad dermatol. 1992;26: 648-50. 4. balus l, amantea a, donati p, fazio m, guiliano mc, bellocci m. fibroelastolytic papulosis of the neck: a report of 20 cases. br j dermatol 1997; 137:461-466 5. patterson a, beasley k, kobayashi t. fibroelastolytic papulosis: histopathologic confirmation of disease spectrum variants in a single case. j cutanpathol. february 2016;43(2):142-147. 6. jagdeo j, ng c, ronchetti ip, wilkel c, betcovitch l, robinson-bostom l. fibroleastolytic papulosis. j am acad dermatol. 2004;51:958-964 7. song yc, oh bh, ko jh, kim jy, hwang yj, lee yw, et al. a case of fibroelastolytic papulosis on the neck of a young man. ann dermatol. 2011;23:193-197 8. maione v, errichetti e, stinco g, orsaria m, and patrone p. fibroelastolytic papulosis of the neck treated with topical tretinoin. j dermatol. aug 2014;(8):758-759 9. wang ar, lewis k, lewis m, robinsonbosom l. papillary dermal elastosis: a unique elastic tissue disorder or an unusual manifestation of pseudoxanthoma elasticum-like papillary dermal elastolysis? j cutanpathol. 2009;36:1010-1013 10. lueangarum s. panchaprateep, r. white fibrous papulosis of the neck treated with fractionated 1550-nm erbium glass laser: a case report. j lasers in med sci. 2016;7940: 256-258 11. ho, d., &jagdeo, j. fractionated carbon dioxide laser treatment of fibroelastolytic papulosis with excellent cosmetic results and resolution of pruritus. jdrugs dermatol. nov 2015; 14(11):1354-1357 conclusion mailto:barriccj@gmail.com 109 three exciting new features aimed at improving the experience of the readers of skin welcome to volume 1, issue 3 of skin: the journal of cutaneous medicinetm. we thank you, the readership of skin, for all of your feedback and suggestions. as a journal made by dermatologists for dermatologists, we are constantly looking for ways to implement new features aimed at serving the needs of the dermatology community. as such, we are excited to announce several new features of that are debuting with the publication of volume 1, issue 3. in order to keep abreast of current trends and issues in the specialty, each future issue will feature a one-on-one interview with a leader in dermatology or industry as part of our new “a view from the top” series, starting with bill humphries, executive vice president of ortho dermatologics. in this section, distinguished individuals will provide insight into the state of the specialty, including current challenges faced by clinicians. also beginning with this issue, we will be highlighting a featured article, selected by the editorial team due to the timeliness and pertinence of the information provided within. we are pleased to announce our first featured article, “acute generalized exanthematous pustulosis in association with hydroxyzine and cetrizine” by nevo, et. al. we believe that this article will provide important new information for the practicing dermatologist. one of our goals at skin is to incorporate the use of technology in order to aid in the widespread dissemination of dermatologic knowledge. with this spirit in mind, we are excited to announce the inclusion of a new section featuring videos of cme lectures with timely information. the first 2 of these video presentations are from the 2017 fall clinical dermatology conference®: “what’s new in the medicine chest, part 1” by james del rosso, do, and “therapeutic update” by gary goldenberg, md. the editors of skin hope that you will find all of these new features to be of value. as always, we look forward to your thoughts and ideas of how we can continue to make skin optimize its value to you. the editors powerpoint presentation presented at the fall clinical dermatology conference for pas & nps (fcpanp23), june 9–11, 2023, orlando, fl, usa figure 8. percentage of patients with investigator-rated tolerability score >0 1.8% 0.6% 1.0% 0.4% 0.0% 0.0% 0 10 20 30 40 50 60 70 80 90 100 baseline week 4 week 12 week 24 week 36 week 52 pa ti en ts , % overall (n=332) n=331 n=324 n=304 n=276 n=255 n=238 figure 5. median duration of iga of clear or almost clear duration of iga 0/1: the time from the first observation of iga 0/1 to the first subsequent time a patient’s iga is not iga 0/1. patients who received vehicle in parent study and rolled over into study 202 with a 0/1 assessment are excluded from this analysis (n=324). iga: investigator global assessment. references 1. dong c, et al. j pharmacol exp ther 2016;358:413–422. 2. lebwohl mg, et al. n engl j med 2020;383:229–239. 3. stein gold ls, et al. poster presented at: innovations in dermatology; march 16-20, 2021; virtual. acknowledgements this study was supported by arcutis biotherapeutics, inc. thank you to the investigators and their staff for their participation in the trial we are grateful to the study participants and their families for their time and commitment writing support was provided by by christina mcmanus, phd, alligent biopharm consulting llc, and funded by arcutis biotherapeutics, inc. disclosures ml, lsg, mjg, kap, lkf, dna, hch, lhk, and mz are investigators and/or consultants for arcutis biotherapeutics, inc. and received grants/research funding and/or honoraria; pb, rh, dk, and db are employees of arcutis biotherapeutics, inc. additional disclosures provided on request. mark lebwohl,1 linda stein gold,2 melinda j. gooderham,3 kim a. papp,4 laura k. ferris,5 david n. adam,6 h. chih-ho hong,7 leon h. kircik,8 matthew zirwas,9 patrick burnett,10 robert higham,10 david krupa,10 david berk10 1icahn school of medicine at mount sinai, new york, ny, usa; 2henry ford medical center, detroit, mi, usa; 3skin centre for dermatology, probity medical research and queen’s university, peterborough, on, canada; 4probity medical research and k papp clinical research, waterloo, on, canada; 5university of pittsburgh, department of dermatology, pittsburgh, pa, usa; 6cca medical research, probity medical research and temerty faculty of medicine, university of toronto, toronto, on, canada; 7probity medical research and university of british columbia, department of dermatology and skin science, surrey, bc, canada; 8icahn school of medicine at mount sinai, new york, ny, indiana medical center, indianapolis, in, physicians skin care, pllc, louisville, ky, and skin sciences, pllc, louisville, ky, usa; 9dermatologists of the central states, probity medical research, and ohio university, bexley, oh, usa; 10arcutis biotherapeutics, inc., westlake village, ca, usa durability of efficacy and safety of roflumilast cream 0.3% in adults with chronic plaque psoriasis from a 52-week, phase 2 open-label safety trial introduction • roflumilast cream, a phosphodiesterase 4 (pde4) inhibitor that is more potent than other pde4 inhibitors,1 was recently approved as a once-daily, nonsteroidal, topical treatment for psoriasis, including intertriginous areas, in patients 12 years of age and older with no limitations on duration of use • in a phase 2b, randomized, double-blind, 12-week trial of 331 adults with chronic plaque psoriasis, roflumilast cream once daily was superior to vehicle cream and was well tolerated2 • the durability of response was assessed in a multicenter, open-label, 52-week study conducted to evaluate long-term safety of roflumilast 0.3% cream in patients with chronic plaque psoriasis methods • this multicenter, open-label, single-arm, long-term, phase 2 safety trial was conducted at 30 centers in the united states and canada • two cohorts of patients were enrolled: cohort 1 patients were those who completed the phase 2b trial through week 12, whereas cohort 2 eligible patients were newly enrolled (treatment-naïve; figure 1) results • patient demographics and clinical characteristics at baseline were similar across cohorts (table 1) • of the 249 subjects who completed trial 201 from sites that participated in this open-label trial, 230 (92.4%) of them enrolled into this study • a 60.5% mean improvement from baseline in psoriasis area severity index (pasi) and 60.1% mean improvement from baseline in body surface area (bsa) affected were observed at week 12 (figures 6 and 7) – results were consistent through week 52 – median bsa at week 52 was 1.0% • safety was consistent with the parent trial (table 2) • 94% of adverse events (aes) were rated mild or moderate in severity • 97% of aes were unrelated or unlikely to be related to treatment as determined by the investigator • ≥97% of patients had no evidence of irritation per investigator local tolerability assessment at each visit (figure 8) conclusions • in this phase 2 long-term safety study, roflumilast cream 0.3%, a once-daily, nonsteroidal topical pde4 inhibitor, was well-tolerated with a safety profile consistent with the parent phase 2b trial (trial 201) – rates of discontinuations due to aes and lack of efficacy were low – no tachyphylaxis occurred and efficacy was consistent over time (iga success, iga 0/1, and percentage change from baseline in bsa and pasi) – of the 185 patients who achieved iga clear/almost clear during the open-label trial, the median durability of iga of clear/almost clear was 10 months (40.1 weeks) figure 4. percentage of patients with i-iga success over time in cohort 23,a acohort 1 not shown because i-iga added as study amendment and numbers of patients evaluated are very small at each timepoint. i-iga: intertriginous-investigator global assessment; i-iga success: i-iga score of clear or almost clear plus 2-grade improvement from baseline. figure 1. study design aexcludes scalp, palms, soles. bsa: body surface area; iga: investigator global assessment; qd: once daily; pasi: psoriasis area severity index; sae: serious adverse event; teae: treatment-emergent adverse event. figure 3. percentage of patients achieving (a) iga success and (b) clear or almost clear as observed. no imputation of missing values. baseline is defined as the last observation prior to the first dose of roflumilast cream in the parent trial (cohort 1 roflumilast 0.3% and roflumilast 0.15% groups) or the current trial (cohort 1 vehicle group and cohort 2). iga: investigator global assessment; iga success = iga score of clear or almost clear plus two-grade improvement from baseline. 42.9 60.0 60.0 56.3 66.7 0 10 20 30 40 50 60 70 80 90 100 week 4 (n=21) week 12 (n=20) week 24 (n=20) week 36 (n=16) week 52 (n=15) pa ti en ts , % table 1. baseline disease characteristics roflumilast 0.15% and 0.3% → roflumilast 0.3% (n=164) cohort 2 and vehicle → roflumilast 0.3% (n=168) overall (n=332) bsa, mean % 6.6 6.0 6.3 pasi, mean 7.2 6.3 7.1 iga score, n (%) 1 (almost clear) 0 (0.0) 8 (4.8) 8 (2.4) 2 (mild) 28 (17.1) 40 (23.8) 68 (20.5) 3 (moderate) 124 (75.6) 110 (65.5) 234 (70.5) 4 (severe) 12 (7.3) 10 (6.0) 22 (6.6) intertriginous involvement (i-iga ≥2) i-iga, n (%) 2 (mild) 14 (8.5) 17 (10.1) 31 (9.3) 3 (moderate) 11 (6.7) 18 (10.7) 29 (8.7) 4 (severe) 1 (0.6) 1 (0.6) 2 (0.6) baseline is defined as the last observation prior to the first dose of roflumilast cream in the parent trial (cohort 1 roflumilast 0.3% and roflumilast 0.15% groups) or the current trial (cohort 1 vehicle group and cohort 2). bsa: body surface area; iga: investigator global assessment; i-iga: intertriginous-iga; pasi: psoriasis area severity index. figure 2. patient disposition atwo patients withdrew from the study due to “other” reasons, which was covid-19 disruption. 32.7 36.7 36.0 30.5 35.3 12.9 36.1 29.3 32.0 37.5 0 10 20 30 40 50 60 70 80 90 100 week 4 week 12 week 24 week 36 week 52 pa ti en ts , % roflumilast 0.15% and 0.3% → roflumilast 0.3% (n=164) cohort 2 and vehicle → roflumilast 0.3% (n=168) roflumilast → roflumilast 162 150 136 128 119 vehicle/naive → roflumilast 163 154 140 129 127 a 40.7 45.3 44.9 39.1 42.0 22.6 48.3 39.1 44.3 47.5 0 10 20 30 40 50 60 70 80 90 100 week 4 week 12 week 24 week 36 week 52 pa ti en ts , % roflumilast 0.15% and 0.3% → roflumilast 0.3% (n=164) cohort 2 and vehicle → roflumilast 0.3% (n=168) roflumilast → roflumilast 162 150 136 128 119 vehicle/naive → roflumilast 163 154 140 129 127 b roflumilast cream phase 2b (trial #201; nct03638258)2 roflumilast cream phase 2 long-term safety (trial #202; nct03764475) eligibility • diagnosis of at least mild plaque psoriasis • age ≥18 years • 2-20% bsaa roflumilast cream 0.3% qd roflumilast cream 0.15% qd vehicle qd endpoints primary: safety • occurrence of teaes • occurrence of saes secondary: efficacy • iga clear or almost clear • intertriginous-iga clear or almost clear • pasi • bsa 12 weeks ra nd om iz at io n 1:1:1 n=331 eligibility • diagnosis of at least mild plaque psoriasis for at least 6 months • age ≥18 years • 2-25% bsaa cohort 1 (rollovers) roflumilast cream 0.3% qd (n=230) 52 weeks cohort 2 (naïve) roflumilast cream 0.3% qd (n=102) completed trial #201 through 12 weeks patients could stop applying treatment to lesions that cleared patients could completely stop treatment when pasi and iga = 0 following an office visit treatment could be resumed when patient-observed psoriasis recurred roflumilast cream 0.3% n=81 roflumilast cream 0.15% n=83 vehicle cream n=66 completed n=244 (73.5%) discontinued: 88 (26.5%) withdrew: 36 (10.8%) lost to follow-up: 34 (10.2%) adverse event: 13 (3.9%) lack of efficacy: 3 (0.9%) other: 2 (0.6%)a cohort 1 cohort 2 enrolled n=332 roflumilast cream 0.3% n=102 figure 6. mean pasi score observed data. no imputation of missing values. pasi assessment was added as an amendment to the trial. pasi: psoriasis area and severity index; sd: standard deviation. figure 7. mean percent bsa affected observed data. no imputations of missing values. baseline is defined as the last observation prior to the first dose of roflumilast cream in the arq-151-202 study. bsa: body surface area; sd: standard deviation. 3.37 2.53 2.56 2.57 2.74 3.34 2.50 2.49 2.60 2.37 0 1 2 3 4 5 6 7 8 9 10 week 4 week 12 week 24 week 36 week 52 m ea n pa si s co re roflumilast 0.15% and 0.3% → roflumilast 0.3% (n=164) cohort 2 and vehicle → roflumilast 0.3% (n=168) roflumilast → roflumilast 17 65 111 128 119 vehicle/naive → roflumilast 101 122 129 129 127 201 parent trial baseline mean (sd) pasi: 7.1 (3.3) cohort 2 baseline mean (sd) pasi: 6.8 (3.3) 2.6 2.3 2.2 2.2 2.2 3.9 2.6 2.4 2.2 2.2 0 1 2 3 4 5 6 7 8 9 10 week 4 week 12 week 24 week 36 week 52 m ea n bs a a ff ec te d, % roflumilast 0.15% and 0.3% → roflumilast 0.3% (n=164) cohort 2 and vehicle → roflumilast 0.3% (n=168) roflumilast → roflumilast 162 150 136 128 119 vehicle/naive → roflumilast 162 154 140 129 127 201 parent trial baseline mean (sd) bsa: 6.15 (3.9) cohort 2 baseline mean (sd) bsa: 6.6 (5.3) scale for investigator-rated local tolerability (0–7) 0 = no evidence of irritation 1 = minimal erythema, barely perceptible 2 = definite erythema, readily visible; minimal edema or minimal papular response 3 = erythema and papules 4 = definite edema 5 = erythema, edema and papules 6 = vesicular eruption 7 = strong reaction spreading beyond application site ~57.1% (n=185) of patients achieved iga 0/1 during the trial; patients have a 50% probability of a duration of iga of clear or almost clear of more than 10 months (40.1 weeks) 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 pr ob ab ili ty ig a c le ar or a lm os t c le ar 4 12 20 28 360 8 16 24 32 44 56 6440 48 6052 censored duration of iga clear or almost clear (weeks) 170 139 114 93 69185 166 123 101 82 41 5 063 37 28at risk table 2. summary of aes (safety population) teae, n (%) roflumilast 0.15% and 0.3% → roflumilast 0.3% (n=164) cohort 2 and vehicle → roflumilast 0.3% (n=168) overall (n=332) patients with any teae 79 (48.2) 85 (50.6) 164 (49.4) patients with any treatment-related teae 4 (1.7) 5 (4.9) 9 (2.7) patients with any sae 8 (4.9) 4 (2.4) 12 (3.6) any treatment-related sae 0 (0) 0 (0) 0 (0) patients who discontinued study drug due to ae 8 (4.9) 5 (3.0) 13 (3.9) most common aes (>2% overall) urti/viral urti 10 (6.1) 12 (7.1) 22 (6.6) nasopharyngitis 6 (3.7) 6 (3.6) 12 (3.6) urinary tract infection 5 (3.0) 6 (3.6) 11 (3.3) sinusitis 3 (1.8) 5 (3.0) 8 (2.4) treatment-emergent adverse event defined as event with an onset on or after the date of the first study drug application in arq-151-202 study. ae: adverse event; sae: serious adverse event; teae: treatment-emergent adverse event; urti: upper respiratory tract infection. • 244 (73.5%) completed the 202 trial of the 332 patients enrolled across cohort 1 (n=230) and cohort 2 (n=102; figure 2) • percentages of patients achieving investigator global assessment (iga) success and an iga of clear or almost clear were consistent over time (figure 3) • among patients with intertriginous area involvement, roflumilast cream provided consistent improvement of intertriginous-investigator global assessment (i-iga; figure 4) • median duration of iga of clear or almost clear was 10 months (figure 5) durability of efficacy and safety of roflumilast cream 0.3% in adults with chronic plaque psoriasis from a 52-week, phase 2 open-label safety trial << /ascii85encodepages false /allowtransparency false /autopositionepsfiles true /autorotatepages /none /binding /left /calgrayprofile (gray gamma 2.2) /calrgbprofile (srgb iec61966-2.1) /calcmykprofile (u.s. web coated \050swop\051 v2) /srgbprofile (srgb iec61966-2.1) /cannotembedfontpolicy /warning 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/namespace [ (adobe) (golive) (8.0) ] /openzoomtohtmlfontsize false /pageorientation /portrait /removebackground false /shrinkcontent true /treatcolorsas /mainmonitorcolors /useembeddedprofiles false /usehtmltitleasmetadata true >> ] >> setdistillerparams << /hwresolution [2400 2400] /pagesize [612.000 792.000] >> setpagedevice ana du, susana raab, margarita yatskayer, stephen lynch l’oréal research and innovation, clark, nj usa a split-face design clinical trial to evaluate the efficacy of a masque when used post-full face fraxel® laser treatment introduction factors such as dermatological or aesthetic procedures, sun or wind exposure, and environmental aggressors can catalyze a state of temporary skin reactivity which leads to the appearance of redness, heat sensations and general discomfort. the goal of the present study was to evaluate the clinical effects of a facial masque designed to comfort and soothe skin following a popular aesthetic procedure. methods graph 1: signs and symptoms as reported by the subjects after masque application and rinse-off. results figure 2: subject showed similar improvement in the appearance of redness to those of the entire panel at post masque rinse-off. baseline/post fraxel® post masque application figure 1: thermal imaging of the treated (subject’s left) and untreated (subject’s right) sites at baseline (postlaser), post-product application and rinse off. the results indicated that the tested masque was effective in improving the appearance of redness (figure 2) and reducing pain/discomfort, burning, heat sensation, and tightness on the treated side post-product application and/or post-product rinse off when compared to baseline and between the treated and untreated sides. (graph 1) results of thermal imaging showed a statistically significant reduction in skin surface temperature on the cheek of the treated side at post-product application and rinse off when compared to baseline (post-laser) and when compared to the untreated side of the face. (figure 1) subjects indicated feeling cool and feeling calmed/soothed immediately upon masque application. conclusions 5292 this single center, split-face clinical trial was conducted over the course of 1 day on thirty (30) female subjects between the ages of 3260. each subject was treated with a fraxel® laser treatment. the tested masque was applied by a clinician on the assigned side of the face according to a predetermined randomization. clinical evaluations of the appearance of redness, dryness, flaking/peeling and swelling were conducted pre-laser, post-laser, postproduct application and post-product rinse off. local cutaneous tolerability was evaluated by subject assessment of signs and symptoms of pain/discomfort, itching, burning, heat sensation and tightness separately for the facial halves. digital images were taken at each of the designated study time points using a thermal camera and visia cr™ system. subjects also completed a questionnaire in regards to the cooling/calming/soothing effects post masque application. -70 -60 -50 -40 -30 -20 -10 0 m ea n % r ed uc tio n pain/discomfort burning heat sensation tightness * * * * * * * * *statistically significant at p>0.05 when compared to baseline and untreated site post masque rinse-off ba se lin e/ po st f ra xe l® post m asque rinse-off treateduntreated the tested masque was effective in improving the appearance of redness following masque application and after rinse-off, reduced skin temperature and soothed signs of discomfort such as pain, burning, heat sensation, and tightness immediately upon masque application, following a fraxel® procedure. treated treateduntreated untreated post masque post rinse-off fc17posterskinceuticalsduasplitfacedesignclinicaltrial.pdf • tumor response was evaluated by central review using modified response evaluation criteria in solid tumors (mrecist) for patients with labcc (figure 2) — includes assessment by magnetic resonance imaging complemented by color photography and histology of multiple biopsy samples; complete response was defined as negative histology with complete disappearance of target lesions by all image modalities7,10 • secondary post hoc assessments included best overall response and duration of response (dor) in patients taking concomitant medications • safety and tolerability were assessed through monitoring and recording adverse events (aes); regular monitoring of hematology, clinical chemistry, and electrocardiograms; and routine monitoring of vital signs and physical condition — aes were coded using medical dictionary for regulatory activities (v19.0) terminology, and toxicity was assessed according to the national cancer institute common terminology criteria for adverse events (v4.03)16 results • at baseline, 60.8% of the 79 patients receiving sonidegib 200 mg/day were male and had a median age of 67.0 years; the majority (83.5%) of patients had labcc and 62.0% had ≥2 lesions (table 1) table 1. baseline demographics and disease characteristics in patients receiving sonidegib 200 mg daily sonidegib 200 mg (n = 79) median age (range), years 67 (25–92) male 48 (61) ecog performance status 0 1 2 unknown 50 (63) 19 (24) 8 (10) 2 (3) stage labcc mbcc 66 (84) 13 (16) histologic/cytologic subtype aggressivea nonaggressiveb undetermined 40 (51) 38 (48) 1 (1) number of lesions 1 ≥2 30 (38) 49 (62) metastasis sites lung bone axillary lymph node trunk otherc 14 (18) 10/14 (71) 2/14 (14) 1/14 (7) 1/14 (7) 3/14 (21) prior antineoplastic therapy surgery radiotherapy 59 (75) 19 (24) data presented as n (%) unless otherwise indicated. aincludes micronodular, infiltrative, multifocal, basosquamous, and sclerosing histological subtypes. bincludes nodular and superficial histological subtypes.cincludes retro-orbital and left mandible, pelvic side wall and lung, and bilateral scalp. bcc, basal cell carcinoma; ecog, eastern cooperative oncology group; labcc, locally advanced bcc; mbcc, metastatic bcc. overall efficacy at 42 months • clinically relevant objective response rates (orrs) continued to be reported for patients receiving 200 mg/day of sonidegib at 42 months (table 2) • at 42 months, the orr (95% confidence interval [ci]) was 48.1% (36.7%–59.6%) for all 79 patients receiving 200 mg/day of sonidegib • disease control rate exceeded 90% and further supports treatment benefit (table 2) • sustained duration was confirmed, with a median duration of response of 26.1 months (table 2) background • incidence of basal cell carcinoma (bcc) is increasing worldwide by an approximate 1% annually1,2 • in cases of advanced bcc, current treatment modalities (eg, surgery) are contraindicated3,4 • hedgehog inhibitors (hhis) were developed to block aberrant hedgehog signaling found in most sporadic bccs, and inhibition of the hedgehog pathway is among the few treatment options available for patients with advanced bcc5,6 • sonidegib—an hhi that selectively targets smoothened1—is approved in the us, the eu, switzerland, and australia for the treatment of adult patients with locally advanced bcc (labcc) not amenable to curative surgery or radiation therapy7-10 — sonidegib is also approved for the treatment of metastatic bcc (mbcc) in switzerland and australia9,10 • through 42 months of the phase 2 bolt (basal cell carcinoma outcomes with lde225 [sonidegib] treatment) trial (nct01327053), sonidegib 200 mg/day demonstrated durable efficacy and consistent/manageable toxicity11-15 objectives • we present a post hoc analysis of efficacy per investigator review in patients with labcc taking common concomitant medications with the approved sonidegib 200 mg/day dose methods • bolt was a randomized, double-blind, phase 2 clinical trial conducted in 58 centers across 12 countries11 (figure 1) figure 1. bolt study design apatients previously treated with sonidegib or other hhi were excluded. bstratification was based on stage, disease histology for patients with labcc (nonaggressive vs aggressive), and geographic region. ctreatment was continued until disease progression, unacceptable toxicity, death, study termination, or withdrawal of consent. ae, adverse event; bolt, basal cell carcinoma outcomes with lde225 (sonidegib) treatment; cr, complete response; dor, duration of response; hhi, hedgehog inhibitor; labcc, locally advanced basal cell carcinoma; mbcc, metastatic basal cell carcinoma; mrecist, modified response evaluation criteria in solid tumors; orr, objective response rate; os, overall survival; pfs, progression-free survival; q8w, every 8 weeks; q12w, every 12 weeks; ttr, time to tumor response. • eligible patients had either histologically confirmed labcc (not amenable to curative surgery or radiation) or mbcc (for which all other treatment options had been exhausted) • primary and secondary endpoints are summarized in figure 2 figure 2. bolt study endpoints bcc, basal cell carcinoma; bolt, basal cell carcinoma outcomes with lde225 (sonidegib) treatment; cr, complete response; dor, duration of response; labcc, locally advanced bcc; mbcc, metastatic bcc; mrecist, modified response evaluation criteria in solid tumors; orr, objective response rate; os, overall survival; pfs, progression-free survival; pr, partial response; ttr, time to tumor response. effect of concomitant medications on efficacy of sonidegib 200 mg daily in patients with locally advanced basal cell carcinoma: results of the 42-month randomized, double-blind bolt study reinhard dummer,1 michael migden,2 nicholas squittieri,3 li liu,3 alexander guminski,4 john lear5 1department of dermatology, university of zürich, skin cancer center, university hospital, zürich, switzerland; 2university of texas md anderson cancer center, departments of dermatology, division of internal medicine, and head and neck surgery, division of surgery, houston, tx, usa; 3royal north shore hospital, st leonards, nsw, australia; 4sun pharmaceutical industries, inc., princeton, nj, usa; 5manchester academic health science centre, university of manchester, manchester, uk orr→ best overall confirmed response of cr or pr per central review according to mrecist (labcc) or recist v1.1 (mbcc)primary dor and cr rates per central review according to mrecist (labcc) or recist v1.1 (mbcc)key secondary • os • safety other secondary • orr and dor per investigator review • pfs and ttr per central and investigator review follow-up (after treatment discontinuation) • tumor response q8w during year 1 and then q12w until progression • subsequent anticancer therapy • aes until 30 days after last dose of sonidegib • survival follow-up q12w until death, lost to followup, or withdrawn consent (and at time of final analysis) endpoints primary: orr (central review) by mrecist (labcc) or recist v1.1 (mbcc) key secondary: dor, cr (central review) other secondary: orr, dor (investigator review); pfs, ttr (central and investigator review); os, safety stratificationb randomization (1:2) sonidegib 200 mg dailyc sonidegib 800 mg dailyc patient populationa • labcc (aggressive and nonaggressive) • mbcc table 2. efficacy outcomes per central review in patients with labcc receiving sonidegib 200 mg daily iabcc (n = 66) orr, % (95% ci) 56.1 (43.3, 68.3) cr, % (95% ci) 4.5 (0.9, 12.7) dcr, % 90.9 dor, median, months (95% ci) 26.1 (ne) pfs, median, months (95% ci) 22.1 (ne) ttr, median, months (95% ci) 4.0 (3.8, 5.6) bcc, basal cell carcinoma; ci, confidence interval; cr, complete response; dcr, disease control rate; dor, duration of response; labcc, locally advanced bcc; mbcc, metastatic bcc; ne, not estimable; orr, objective response rate; pfs, progression-free survival; ttr, time to tumor response. • overall orr (95% ci) by investigator review for patients with labcc receiving sonidegib 200 mg/day (n = 66) was 71.2% (58.7%–81.7%, table 3) • median dor (95% ci) per investigator review for patients with labcc receiving sonidegib 200 mg/day was 15.7% (12.0%– 20.2%, table 3) table 3. objective response rate and duration of response per investigator review in patients with labcc receiving sonidegib 200 mg daily all labcc patients (n = 66) aggressive histology (n = 37) nonaggressive histology (n = 29) orr (95% ci) 71.2 (58.7–81.7) 70.3 (53.0–84.1) 72.4 (52.8–87.3) dor (95% ci) 15.7 (12.0–20.2) 20.2 (ne) 15.7 (11.0–20.2) ci, confidence interval; dor, duration of response; labcc, locally advanced basal cell carcinoma; ne, not estimable; orr, objective response rate. efficacy in patients taking concomitant medications and sonidegib 200 mg/day • the orr for patients receiving sonidegib 200 mg/day and concomitant medications were comparable to all patients receiving only sonidegib 200 mg/day • patients receiving salicylic acid derivatives had the highest orr of patients taking common concomitant medications (table 4) table 4. best overall response, progression-free survival, and time to tumor response per investigator review in patients with labcc receiving concomitant medications and sonidegib 200 mg daily any concomitant medications (n = 37) nsaids (n = 7) glucocorticoids (n = 10) sads (n = 9) orr (95% ci) 73.0 (55.9–86.2) 71.4 (29.0–96.3) 80.0 (44.4–97.5) 88.9 (51.8–99.7) cr, % (95%, ci) 2.7 (0.1–14.2) 0 (0–41.0) 0 (0–30.8) 0 (0–33.6) dcr, % 94.6 100.0 100.0 100.0 pfs, median (95%, ci) 39.6 (ne) ne ne 19.0 (ne) ttr, median (95% ci) 3.9 (2.1–6.6) 1.9 (ne) 3.9 (1.9–9.3) 5.6 (1.9–7.4) ci, confidence interval; cr, complete response; dcr, disease control rate; labcc, locally advanced basal cell carcinoma; ne, not estimated; nsaid, nonsteroidal anti-inflammatory drug; orr, objective response rate; pfs, progression-free survival; sad, salicylic acid derivative; ttr, time to tumor response. • overall, 26.3% of patients taking common concomitant medications along with sonidegib 200 mg/day had progressive disease (table 5) table 5. duration of response per investigator review in patients with labcc receiving concomitant medications and sonidegib 200 mg daily any concomitant medications (n = 37) nsaids (n = 7) glucocorticoids (n = 10) sads (n = 9) n/n1 5/19 3/5 3/8 2/9 pds, n (%) 5 (26.3) 2 (40) 2 (25) 2 (22) dor, median, months (95% ci) ne (ne) 12.9 (3.4–13.6) 18.2 (ne) ne (ne) ci, confidence interval; dor, duration of response; labcc, locally advanced basal cell carcinoma; ne, not estimated; nsaid, nonsteroidal anti-inflammatory drug; orr, objective response rate; pd, progressive disease; sad, salicylic acid derivative. safety and tolerability • the safety profile of sonidegib 200 mg/day was manageable and consistent with previous analysis1-5 • at 42 months, 64/66 (97.0%) patients with labcc receiving sonidegib 200 mg/day experienced an ae • the most frequent aes in this population were muscle spasms (54.4%), alopecia (49.4%), dysgeusia (44.3%), and nausea (39.2%) • the majority of aes were grade 1–2 in severity (figure 3) figure 3. adverse events reported in ≥20% of patients receiving sonidegib 200 mg daily ck, creatine kinase. conclusions • sonidegib 200 mg/day led to clinically meaningful outcomes in patients with labcc through 42 months of treatment, with a manageable tolerability profile11-15 • common concomitant medications had no impact on efficacy • the safety profile of sonidegib 200 mg daily was manageable and consistent with previous analysis11,13 references 1) xiang f, et al. jama dermatol. 2014; 150:1063–71; 2) asgari mm, et al. jama dermatol. 2015; 151:976–81; 3) amici jm, et al. eur j dermatol. 2015; 25:586–94; 4) lear jt, et al. br j cancer. 2014; 111:1476–81; 5) cortes je, et al. cancer treat rev. 2019; 76:41–50; 6) kim jys, et al. j am acad dermatol. 2018; 78:540–59; 7) odomzo (sonidegib) [package insert]. cranbury, nj: sun pharmaceutical industries, inc.; 2017; 8) european medicines agency. summary of product characteristics, wc500188762; 9) swissmedic, authorization number 65065, 2015; 10) australian government department of health, artg 292262; 11) migden mr, et al. lancet oncol. 2015; 16:716–28; 12) migden mr, et al. j clin oncol. 2018; 36:suppl abstr 9551; 13) lear jt, et al. j eur acad dermatol venereol. 2018; 32:372–81; 14) dummer r, et al. j am acad dermatol. 2016; 75:113–25.e115; 15) dummer r, et al. br j dermatol. 2019; 10.1111/bjd.18552; 16) national cancer institute. common terminology criteria for adverse events v4.03. acknowledgments medical writing and editorial support were provided by jennifer meyering, rn, ms, cmpp, of alphabiocom, llc, and funded by sun pharmaceutical industries, inc. disclosures mm has participated on advisory boards and received honoraria from genentech; novartis pharmaceuticals corporation; sun pharmaceutical industries, inc.; and regeneron pharmaceuticals. jl has received personal fees from novartis pharmaceuticals corporation. ll and ns are employees of sun pharmaceutical industries, inc. ag has participated on advisory boards for bristol-myers squibb, pfizer, and sanofi; received honoraria from novartis pharmaceuticals corporation; and received travel support from astellas and bristol-myers squibb. rd has received grants and personal fees from bristol-myers squibb; glaxosmithkline; merck sharpe and dohme; novartis pharmaceuticals corporation; roche; and sun pharmaceutical industries, inc. 0 20 40 60 decreased appetite ck increased weight decreased diarrhea fatigue nausea dysgeusia alopecia muscle spasm percent of patients grade 3-4 grade 1-2 51.9 49.4 44.3 38.0 31.6 30.4 25.3 24.1 21.5 54.4 49.4 44.3 39.2 32.9 31.6 30.4 30.4 22.8 presented at fall clinical dermatology conference for pas & nps 2020, april 3–5, orlando, fl, usa 47 what’s new in the medicine chest? part 2 james del rosso, do video length: 17:26 video description: in a cme podium lecture presented at the 2017 fall clinical dermatology conference® in las vegas, nevada, james del ross, do, reviews recent advances in dermatopharmacology. topics highlighted include new and emerging therapies for atopic dermatitis, acne vulgaris, rosacea, actinic keratosis, seborrheic keratosis, and axillary hyperhidrosis. presented at the 40th annual fall clinical dermatology conference (fall cdc 2020); virtual congress; october 29 – november 1, 2020. background • dupilumab is a fully human monoclonal antibody1,2 that blocks the shared receptor component for interleukin-4 and interleukin-13 and has a demonstrated safety profile and sustained efficacy in adult and pediatric patients (aged ≥ 6 years) with moderate-to-severe atopic dermatitis (ad)3–6 • there is currently a paucity of information on patients who receive dupilumab in a real-world setting • we present baseline data from a real-world registry of adult ad patients, initiating commercial dupilumab treatment for ad per approved prescribing information objective • to report baseline disease severity and treatment burden of ad in patients initiating dupilumab using data from the prose registry baseline characteristics of atopic dermatitis (ad) and ad treatments in a cohort of adult ad patients initiating dupilumab in a real-world registry (prose) daniel i. shrager1, scott guenthner2, david cohen3, haixin zhang4, daniel richman5, andrew korotzer4, shikha bansal4 1alpha dermatology of pa, llc, sellersville, pa; 2the indiana clinical trials center, pc, plainfield, in; 3skin care physicians of georgia, macon, ga; 4regeneron pharmaceuticals, inc., tarrytown, ny; 5sanofi genzyme, cambridge, ma; usa conclusions • patients initiating dupilumab in routine clinical practice had significant burden of disease as determined by both patientand clinician-assessed outcomes of ad lesions and quality of life • ad symptomology extended beyond itch and included skin sensitivity to touch and disturbances to sleep • more than half of the patients in prose were on ≥ 1 medication at study baseline, that included oral and topical corticosteroids and systemic ad treatments, signifying a high treatment burden references: 1. macdonald le, et al. proc natl acad sci u s a. 2014;111:5147-52. 2. murphy aj, et al. proc natl acad sci u s a. 2014;111:5153-8. 3. blauvelt a, et al. lancet. 2017;389:2287-303. 4. de bruin-weller m, et al. br j dermatol. 2018;178:1083-101. 5. simpson el, et al. n engl j med. 2016;375:2335-48. 6. beck la, et al. am j clin dermatol. 2020;21:567-77. acknowledgments: research sponsored by sanofi and regeneron pharmaceuticals, inc. clinicaltrials.gov identifier: nct03428646. medical writing/editorial assistance provided by toby leigh bartholomew, phd, of excerpta medica, funded by sanofi genzyme and regeneron pharmaceuticals, inc. disclosures: shrager di: regeneron pharmaceuticals, inc. – investigator. guenthner s: abbvie, amgen, encore dermatology, genentech, janssen, leo pharma, eli lilly, pfizer, sun pharma, ucb – investigator and/or speaker. cohen d: abbvie, amgen, eli lilly, jansen, leo pharma, novartis, ortho dermatologics, regeneron pharmaceuticals, inc., sanofi, sun pharma, ucb – advisor and speaker. zhang h, korotzer a, bansal s: regeneron pharmaceuticals, inc. – employees and shareholders. richman d: sanofi genzyme – employee, may hold stock and/or stock options in the company. methods study design • prose (nct03428646) is a multicenter, longitudinal, prospective, up-to-5-years observational registry in the usa and canada characterizing patients receiving dupilumab treatment for ad in a real-world setting • standard ad investigator assessments as well as patientreported outcomes were utilized • the investigator-led overall disease severity (ods) instrument was introduced on an exploratory basis – ods is a 5-point categorical tool that takes all important aspects characterizing ad severity into account at a given timepoint • baseline data were recorded on the date at which dupilumab treatment was initiated table 1. baseline demographics. n = 315 age, mean (sd), years 42.5 (16.99) female sex, n (%) 174 (55.2) race, n (%) white 187 (59.4) black or african american 56 (17.8) asian 51 (16.2) othera 7 (2.2) not reported 14 (4.4) height, mean (sd), cm 168.03 (10.27) weight, mean (sd), kg 79.72 (20.60) bmi, mean (sd), kg/m2 28.24 (7.23) aincludes american indian or alaskan native and native hawaiian or other pacific islander. bmi, body mass index; sd, standard deviation. table 2. summary of current medication. therapeutic class chemical class n = 315 ≥ 1 current medication 182 (57.8) corticosteroids, dermatological preparations 81 (25.7) moderately potent (group ii) 43 (13.7) potent (group iii) 24 (7.6) very potent (group iv) 26 (8.3) moderately potent in combination with antibiotics 1 (0.3) corticosteroids for systemic use 39 (12.4) glucocorticoids 37 (11.7) anticorticosteroids 2 (0.6) other dermatological preparations 63 (20.0) agents for dermatitis, excluding corticosteroids 61 (19.4) antihidrotics 2 (0.6) other 2 (0.6) all data are reported as number of patients (%). classification is based on the world health organization drug dictionary, march 2019 b3 format. table 4. disease characteristic analysis by baseline ods. baseline ods no disease (n = 2) minimal disease (n = 4) mild disease (n = 26) moderate disease (n = 176) severe disease (n = 105) missing (n = 2) total (n = 315) baseline easi total score 0 3.18 (2.49) 3.93 (2.60) 13.41 (8.58) 26.66 (15.45) 30.00 (n/a) 16.90 (13.36) baseline poem total score 7.0 (n/a) 2.0 (0) 16.9 (5.82) 17.8 (6.77) 20.6 (5.72) n/a (n/a) 18.5 (6.65) baseline dlqi total score 1.0 (n/a) 1.5 (2.12) 10.4 (7.19) 11.5 (7.22) 15.5 (7.19) n/a (n/a) 12.7 (7.52) all values are mean (sd). n/a, not available. methods (cont.) results (cont.) analysis • data presented here are from the first interim analysis set of adult patients receiving dupilumab (data cutoff: july 2019) • all analyses are descriptive, without imputation for missing values • at baseline, 57.8% of patients were using ≥ 1 medication, including topical corticosteroids that were used by 25.7% of patients (table 2) – 12.4% of patients used systemic corticosteroids (table 2) disease characterization • the mean duration of ad was 19.7 years, with mean easi of 16.9 (table 3) • mean poem score was 18.5 (on a scale of 0 to 28) and mean dlqi was 19.0 (on a scale of 0 to 30), consistent with moderate-to-severe ad (table 3) table 3. baseline disease characteristics. n = 315 ad duration, mean (sd), years 19.7 (17.30) easi, mean (sd), n1 16.90 (13.36), 314 ods, n (%) no disease (scale = 0) 2 (0.6) minimal disease (scale = 1) 4 (1.3) mild disease (scale = 2) 26 (8.3) moderate disease (scale = 3) 176 (55.9) severe disease (scale = 4) 105 (33.3) missing 2 (0.6) bsa affected by ad, mean (sd), %, n1 26.76 (23.670), 313 peak pruritus nrs, mean (sd), n1 6.9 (2.30), 227 peak pruritus nrs ≥ 3, n/n1 (%) 215 (68.3) skin pain/soreness nrs, mean (sd), n1 5.3 (2.99), 227 skin pain/soreness nrs ≥ 3, n (%) 177 (56.2) skin feeling hot nrs, mean (sd), n1 4.6 (3.09), 226 skin feeling hot nrs ≥ 3, n (%) 157 (49.8) skin sensitivity nrs, mean (sd), n1 5.1 (3.17), 227 skin sensitivity nrs ≥ 3, n (%) 166 (52.7) sleep disturbance nrs, mean (sd), n1 5.4 (3.26), 224 sleep disturbance nrs ≥ 3, n (%) 171 (54.3) poem, mean (sd), n1 18.5 (6.65), 233 dlqi, mean (sd), n1 19.0 (7.71), 227 pgad, n (%) poor (scale = 1) 5 (1.6) fair (scale = 2) 22 (7.0) good (scale = 3) 77 (24.4) very good (scale = 4) 69 (21.9) excellent (scale = 5) 53 (16.8) missing 89 (28.3) bsa, body surface area; dlqi, dermatology life quality index; easi, eczema area and severity index; n1, number of patients with measurement; nrs, numerical rating scale; ods, overall disease severity; pgad, patient global assessment of ad; poem, patient-oriented eczema measure. results baseline demographics and current treatment use • 315 patients were enrolled in the prose cohort at data cutoff • patient demographics are shown in table 1 – the mean age was 42.5 years; 55.2% of patients were female; and 59.4% white • most patients reported significant skin and sleep disturbance symptoms; 68.3% of patients had peak pruritus nrs scores of 3 or more (table 3) – the proportions of patients with scores ≥ 3 in skin pain/ soreness nrs, skin feeling hot nrs, skin sensitivity to touch nrs and sleep disturbance nrs were 56.2%, 49.8%, 52.7%, and 54.3%, respectively (table 3) – one-quarter of patients assessed their disease status as “good” at baseline (table 3) • there was a tendency for baseline easi, poem scores, and dlqi to increase with severity assessed according to ods (table 4) _hlk532340640 _hlk20913887 acknowledgements: medical writing support was provided by prescott medical communications group (chicago, il) with financial support from ortho dermatologics; ortho dermatologics is a division of bausch health us, llc • presented at fall clinical 2020 • october 29 november 1, 2020 • virtual synopsis ◾ psoriasis is a chronic, inflammatory skin disorder characterized by abnormal differentiation/hyperproliferation of keratinocytes, infiltration of immune cells in the dermis and epidermis, and increased capillary density1,2 ◾ a fixed combination halobetasol propionate 0.01%/tazarotene 0.045% (hp/taz) lotion (duobrii,® ortho dermatologics) was developed to address unmet needs in the topical treatment of psoriasis (see inset) • topical corticosteroids—such as hp—are the mainstay of treatment, though long-term safety remains a concern, limiting use3 • the topical retinoid taz has demonstrated efficacy by modulating major causes of psoriasis and maintaining therapeutic effect, though taz may induce cutaneous irritation3-6 • treating psoriasis by combining hp with taz may enhance efficacy, reduce side effects of both hp and taz, and sustain treatment response posttreatment3,6 objective ◾ to investigate maintenance of effect posttreatment following once-daily application of hp/taz lotion in patients with moderate-to-severe psoriasis who achieved clear skin methods ◾ this was a 1-year, multicenter, open-label study (nct02462083) in participants ≥18 years of age with moderate-to-severe plaque psoriasis (investigator’s global assessment [iga] score of 3 or 4 and affected body surface area [bsa] of 3–12%) ◾ participants were treated with hp/taz lotion once daily for 8 weeks and intermittently as needed in 4-week intervals (figure 1) • at week 8, treatment was stopped for participants who achieved treatment success (iga score of clear [0] or almost clear [1]); all other participants were treated for an additional 4 weeks • all participants were re-evaluated at week 12 for improvement; maximum continuous exposure was 24 weeks ◾ in this study, cerave® hydrating cleanser and cerave® moisturizing lotion (l’oreal, ny) were provided as needed for optimal moisturization/ cleaning of the skin ◾ a post hoc analysis evaluated maintenance of effect in participants who were enrolled ≥8 weeks and who achieved an iga score of 0 (clear) during the study long-term management of moderate-to-severe plaque psoriasis: maintenance of treatment success following cessation of halobetasol propionate 0.01%/tazarotene 0.045% lotion figure 1. open-label study design oncedaily hp/taz for 8 weeks successa treatment stopped for 4 weeks if 24 weeks of continuous treatment were received at any point in the study and the participant did not achieve an iga score of 0 or 1, the participant was discontinued from the study. day 0 continued study and managed in 4-week cycles for up to 1 year, with participants re-evaluated every 4 weeks for treatment successa • successa: treatment stopped for 4 weeks • no success: continued once-daily hp/taz for 4 weeks week 8 week 12 week 24 week 52 no success continued once-daily hp/taz for 4 weeks discontinued from study no improvement screening evaluated for treatment successa at week 8 evaluated for improvementb at week 12 improvement atreatment success defined as score of 0 (clear) or 1 (almost clear) on iga. bimprovement defined as ≥1-grade improvement from baseline iga; those demonstrating improvement continued the study and were subsequently managed in 4-week cycles (eg, treated with hp/taz lotion once-daily if they had not achieved treatment success or receiving no treatment until the next evaluation if they had achieved treatment success). maximum continuous exposure was 24 weeks. hp/taz, halobetasol propionate 0.01%/tazarotene 0.045%; iga, investigator’s global assessment. results ◾ a total of 555 participants in this study were treated with hp/taz and 550 had post-baseline safety data • mean age was 51.9 years, 65.6% were male, and 86.0% were white • at baseline, 86.5% had an iga score of 3 (moderate) and 13.5% had iga of 4 (severe); mean bsa was 5.6% ◾ overall, 318 participants (57.8%) achieved treatment success at some point during the study; 54.4% of those did so within the first 8 weeks participants achieving clear ◾ fifty-six participants were enrolled in the study for at least 8 weeks and achieved an iga score of 0 (clear) at ≥1 visit ◾ of these participants: 28.6% did not require any hp/taz retreatment after first achievement of clear, 53.6% did not require retreatment for ≥85 days, 62.5% for ≥57 days, and 83.9% for ≥29 days (figure 2) linda stein gold, md1; mark g lebwohl, md2; neal bhatia, md3; douglas diruggiero, pa-c4; abby jacobson, ms, pa-c5; radhakrishnan pillai, phd6 1henry ford hospital, detroit, mi; 2icahn school of medicine at mount sinai, new york, ny; 3therapeutics clinical research, san diego, ca; 4skin cancer & cosmetic dermatology, rome, georgia; 5ortho dermatologics*, bridgewater, nj; 6bausch health us, llc*, petaluma, ca *bausch health us, llc is an affiliate of bausch health companies inc. ortho dermatologics is a division of bausch health us, llc. figure 2. time to retreatment with hp/taz after first achievement of clear on or after week 8 (n=56a) p e rc e n ta g e o f p a rt ic ip a n ts (c u m u la ti ve ) 0% 20% 40% 60% 80% 100% 28.6% 39.3% 53.6% 62.5% 83.9% no retreatment (no relapse) no retreatment for >16 weeks no retreatment for >12 weeks no retreatment for >8 weeks no retreatment for >4 weeks aparticipants still enrolled post 8 weeks in the study and who stopped therapy after achievement of clear; per the study design, all participants stopped treatment after achievement of clear or almost clear. cumulative data shown; participants included in the bar graphs are not mutually exclusive. hp/taz, halobetasol propionate 0.01%/tazarotene 0.045%. conclusions ◾ in this 1-year, open-label study of hp/taz, 53.6% of participants who achieved clear skin (iga score of 0) did not require retreatment for more than 12 weeks • results are notable given a limitation of the study design, in which participants were required to stop using hp/taz lotion at the time of first treatment success (achievement of clear or almost clear) • this may have reduced the total number of participants who could have achieved clear skin with continued hp/taz treatment, potentially also reducing the duration of time to retreatment ◾ these data indicate a long maintenance of therapeutic effect with hp 0.01%/ taz 0.045% lotion in participants who achieved clear skin, likely due to the role of taz in sustaining efficacy posttreatment (see inset) references 1. nestle fo, et al. n engl j med. 2009;361(5):496-509. 2. benhadou f, et al. dermatology. 2019;235(2):91-100. 3. tanghetti e, et al. j dermatolog treat. 2019:1-8. 4. chandraratna ra. j am acad dermatol. 1997;37(2 pt 3):s12-17. 5. duvic m, et al. j am acad dermatol. 1997;37(2 pt 3):s18-24. 6. tanghetti e, et al. j drugs dermatol. 2018;17(12):1280-1287. author disclosures lsg has served as investigator/consultant or speaker for ortho dermatologics, leo, dermavant, incyte, novartis, abbvie, and lilly. ml is an employee of mount sinai and receives research funds from abbvie, amgen, arcutis, astrazeneca, boehringer ingelheim, celgene, clinuvel, eli lilly, incyte, janssen research & development, llc, kadmon corp., llc, leo pharmaceuticals, medimmune, novartis, ortho dermatologics, pfizer, sciderm, ucb, inc., and vidac, is a consultant for allergan, almirall, arcutis, inc., avotres therapeutics, birchbiomed inc., boehringer-ingelheim, bristol-myers squibb, cara therapeutics, castle biosciences, corrona, dermavant sciences, foundation for research and education in dermatology, inozyme pharma, leo pharma, meiji seika pharma, menlo, mitsubishi, neuroderm, pfizer, promius/dr. reddy’s laboratories, theravance, and verrica. nb has received honoraria and investigator grants from bausch health. wc has nothing to disclose; aj is an employee of ortho dermatologics and may hold stock and/or stock options in its parent company. rp is an employee of bausch health us, llc and may hold stock and/or stock options in its parent company. why tazarotene + halobetasol? tazarotene mechanism of action in psoriasis4,5 ◾ tazarotene is a retinoid prodrug that is rapidly metabolized to tazarotenic acid, which binds with high affinity to ligand-dependent transcription factors rarγ (enriched in the skin) and rarβ ◾ tazarotene modulates pathogenic factors of psoriasis, thereby appearing to restore skin to a more quiescent, prelesional status (figure) ◾ this “normalization” of keratinocytes may be the basis of the relatively long remission after tazarotene treatment upregulation of genes downregulation of signal transduction pathways keratinocyte proliferation keratinocyte proliferation expression of in�ammatory makers (decreasing dermal in�ltration of immune cells) normalization of abnormal keratinocyte differentiation ta rar rar, retinoic acid receptor; ta, tazarotenic acid (active metabolite of tazarotene). fixed-combination hp 0.01%/taz 0.045% lotion formulation3,6 ◾ innovative polymeric emulsion technology formulation allows for uniform distribution of active ingredients in a lower-dose formulation (figure) ◾ vehicle lotion formulation is non-greasy and provides enhanced barrier to the skin ◾ application of hp/taz lotion results in higher permeation efficiency of the active ingredients compared with application of higher-dose hp or taz creams (alone or layered) 1-2 μm 3-d mesh allows for uniform distribution of active ingredients and moisturizing agents droplets consisting of active ingredients (hp and taz) and oil soluble moisturizing agents held apart by the 3-d mesh 25-50 μm 3-d mesh (polymeric matrix) holding water and water soluble hydrating agents within the mesh hp, halobetasol propionate; taz, tazarotene. combining taz + hp may enhance efficacy, reduce side effects, and sustain treatment response posttreatment3,6 powerpoint presentation • ak lesion count to day 57 is shown in figure 2. reduction in ak lesion count to day 57 was significantly greater than vehicle for all post-baseline visits until day 57 (table 2). • eligible subjects, predominantly caucasian males with mean age of 70, skin type iii and had median of 6 ak in the treatment area, were randomized to receive tirbanibulin (n=353) or vehicle ointment (n=349). over 99% completed treatment. baseline characteristics are shown in table 1. results andrew blauvelt1, steven kempers2, todd schlesinger3, edward lain4, hui wang5, david cutler5, mark lebwohl6, jane fang5, rudolf kwan5 1oregon medical research center, portland, or, usa;2minnesota clinical study center, new brighton, mn, usa;3clinical research center of the carolinas, charleston, sc, usa;4austin institute for clinical research, pflugerville, tx, usa;5athenex, inc., buffalo, ny, usa;6icahn school of medicine at mount sinai, new york, ny, usa. tirbanibulin ointment 1% for actinic keratosis (ak): pooled data from two phase 3 studies • here we present pooled data analyses on efficacy, safety and 1-year follow-up. objective • writing support was provided by tfs s.l. • this study was sponsored by athenex, inc.. acknowledgements conclusions • tirbanibulin ointment 1% applied for 5 days was well tolerated, safe and effective, potentially making it a valuable new addition to ak treatment. figure 1. complete and partial clearance rates of ak lesions (itt population) • primary and secondary endpoints were complete (100%) and partial (≥75%) clearance of ak lesions at day (d) 57. • safety including adverse events (aes) and local skin reactions (lsrs; grade 0[none]-3[severe]) was assessed up to d57. composite lsr scores represents the grades sum of all 6 lsr categories with a possible range from 0 to 18. • subjects with complete ak clearance at d57 were followed for 1-year to assess safety and clearance durability. methods • two identical phase 3 randomized, double-blinded, vehicle-controlled studies evaluated efficacy and safety of tirbanibulin ointment 1% vs. vehicle in adults with ak on face/scalp. • eligible subjects with 4‒8 clinically visible ak lesions in a 25 cm2 area were randomized 1:1 to receive tirbanibulin or vehicle (5-day once-daily selfapplication). • lsr signs were present at baseline, increased after treatment, peaked on d8 with tirbanibulin, decreased significantly by d15, and mostly resolved by d29. • maximum mean±sd composite lsr scores were 4.1±2.32 and 1.0±1.14 for tirbanibulin and vehicle group, respectively. • lsrs were mostly transient mild or moderate erythema and flaking/scaling. severe lsrs were few. all lsrs resolved or returned to baseline and did not require intervention. • no deaths, discontinuations, or serious aes related to tirbanibulin occurred. • no treatment-related aes throughout 1-year follow-up were reported. • tirbanibulin is a novel inhibitor of tubulin polymerization, also associated with disruption of src kinase signaling, developed as a topical formulation for ak. we have previously shown that 5 days of tirbanibulin ointment is safe and superior to vehicle in ak clearance at 2 months post-treatment in two phase 3 studies (fcd 2019). synopsis • treatment-related aes were few and mostly mild transient application-site pruritus (tirbanibulin vs. vehicle: 9% vs 6%) and pain (tirbanibulin vs vehicle: 10% vs 3%) (table 3). table 1. baseline characteristics tirbanibulin (n=353) vehicle (n=349) mean age (sd), years 69.3 (8.61) 70.2 (9.13) gender: male, n (%) 305 (86) 304 (87) race: white, n (%) 352 (>99) 348 (>99) fitzpatrick skin type, n (%) type i 49 (14) 38 (11) type ii 200 (57) 224 (64) type iii 88 (25) 79 (23) type iv 15 (4) 7 (2) type v 0 1 (<1) type vi 1 (<1) 0 median baseline ak lesion count (min max) 6.0 (4 8) 6.0 (4 8) ak, actinic keratosis; sd, standard deviation 40th annual fall clinical dermatology conference, october 29 november 1, 2020 safety population (n=702) n (%) tirbanibulin (n=353) vehicle (n=349) number of subjects with any treatment-related aes 56 (16%) 35 (10%) application site pain 35 (10%) 11 (3%) application site pruritus 32 (9%) 21 (6%) table 3. treatment-related adverse events up to day 57 (safety population) partial clearancecomplete clearance 9 18 49 72 0 10 20 30 40 50 60 70 80 % p a ti e n ts vehicle tirbanibulin vehicle tirbanibulin p<0.0001 δ =54 p<0.0001 δ =40 vehicle (n=349) tirbanibulin (n=353) 0 1 2 3 4 5 6 baseline day 8 day 15 day 29 day 57 tirbanibulin vehicle day 8baseline day 15 day 29 day 57 n u m b e r o f a k l e s io n s ( m e a n ± s e ) figure 2. number of lesions by visit and treatment group up to day 57 ak, actinic keratosis; se, standard error • at 1-year post-d57 follow-up, kaplan-meier estimate of proportion of tirbanibulintreated patients (n=174) with at least one recurrent lesion present at baseline in the treated area recurring during follow-up was 47% and estimated rate of subjects with any ak lesion (recurred or new) was 73% (figure 3). a total of 27% of patients had sustained ak clearance at 1-year. tirbanibulin (n=353) vehicle (n=349) baseline mean (±se) 5.90 (0.07) 5.85 (0.07) day 8 mean (±se) 3.87 (0.15) 4.75 (0.11) change from baseline, mean (%) -2.05 (-35%) -1.10 (-19%) p-value <0.0001 day 15 mean (±se) 2.51 (0.13) 4.52 (0.12) change from baseline -3.38 (-58%) -1.33 (-24%) p-value <0.0001 day 29 mean (±se) 1.68 (0.10) 4.37 (0.12) change from baseline -4.23 (-72%) -1.48 (-26%) p-value <0.0001 day 57 mean (±se) 1.29 (0.10) 4.14 (0.13) change from baseline -4.61 (-79%) -1.72 (-31%) p-value <0.0001 table 2. summary of ak lesion counts up to day 57 ak, actinic keratosis; se, standard error • at d57, complete clearance rates were significantly higher with tirbanibulin vs. vehicle, 49% vs. 9% (p<0.0001); partial clearance rates were 72% vs.18%, respectively (p<0.0001) (figure 1). median reduction in ak lesion count at d57 was greater with tirbanibulin vs. vehicle (87.5% vs. 20%). figure 3. proportion of patients with any recurrence by number of lesions at baseline 26,5 45,9 44,7 52,6 31,8 40,8 17,6 14,8 18,4 21,1 45,5 20,7 2,9 8,2 7,9 10,5 13,6 8,0 2,9 5,3 1,1 4,5 0,6 0,0 20,0 40,0 60,0 80,0 100,0 1 lesion 2 lesions 3 lesions 4 lesions 6 lesions 89.5 at recurrence 4 lesions 5 lesions 6 lesions 7 lesions 8 lesions total 50.0 68.9 71.1 (n=34) (n=61) (n=38) (n=19) (n=22) (n=174) 71.3 p ro p o rt io n o f p a ti e n ts 95.5 proportion of patients with x lesions at baseline skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 613 brief articles elephantiasis nostras verrucosa: a case series graham h litchman, do, ms1; lauren schwartzberg, bs2; suzanne friedler, md1,3; suzanne sirota rozenberg, do, faocd, faad1 1department of dermatology, st. john’s episcopal hospital, far rockaway, new york 2new york institute of technology, college of osteopathic medicine, glen head, new york 3department of dermatology, mount sinai, new york, new york secondary lymphedema is caused by extralymphatic disease processes including trauma, infection, congestive heart failure, obesity, malignancy, and venous stasis.1 an uncommon complication of longstanding secondary lymphedema is elephantiasis nostras verrucosa (env). delayed identification and treatment of this disease process can lead to poor patient outcomes, (e.g. deformity/impairment of limbs, localized infections and lymphangitis, or stewarttreves syndrome).1 here we present two patients with env that span a spectrum of disease severity to facilitate medical providers identification of the disease and assessment of disease progression so that they can take early intervention and improve patient outcomes and satisfaction. patient 1 is a 74-year-old woman with a relevant past medical history of poorlycontrolled diabetes on insulin, hypertension on amlodipine, and hyperlipidemia who presented to the dermatology clinic with 6 months of bilateral leg swelling and xerosis. the patient denied using any home remedies, prior treatments, and reported no pertinent travel or family history. relevant medications included baby aspirin, furosemide, amlodipine, irbesartan, atorvastatin, and insulin. physical examination revealed verrucous nodules and plaques scattered over bilateral lower legs down to the ankle (figures 1a and 1b) with concomitant non-pitting edema of bilateral lower extremities and a positive kaposistemmer sign on bilateral 2nd toes. sensation was intact, but the surrounding skin was warm and tender. initial management included leg elevation, compression stockings, triamcinolone acetonide 0.1% ointment, and topical ammonium lactate. patient 2 is a 75-year-old man with a past medical history significant for hypothyroidism, hypertension on amlodipine, congestive heart failure (chf), hepatitis c abstract elephantiasis nostras verrucosa (env) is a rare complication of chronic lymphedema that can cause significant disfiguration of the affected body part. we present a case series of two patients encompassing a spectrum of env severity to help medical providers become more comfortable identifying and managing env, with the goal of ultimately improving patient outcomes. introduction case presentation skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 614 figure 1. (a) patient 1’s left lower leg; hyperpigmented verrucous plaques, scaling fissures, and significant xerosis. (b) patient 1’s right lower leg demonstrating hyperpigmented and pink verrucous plaques with cobblestoning. figure 2. (a): patient 2’s left lower leg demonstrating cobblestoning with pink verrucous plaques and impetiginization. (b): patient 2’s right lower leg demonstrating cobblestoning with pink verrucous plaques and impetiginization induced cirrhosis now 6 years status post liver transplant, and stroke who presented to the dermatology clinic with bumps on his legs for one year. he reported that these bumps were increasing in number and spreading proximally up his lower legs. the patient had been using a topical collagenase and sodium chloride 0.9% that mildly alleviated his symptoms for a short period. relevant medications included warfarin, levothyroxine, tacrolimus, metoprolol, amlodipine, and furosemide. physical exam revealed bilateral lower extremity cobblestoning with erythema and diffuse honey-colored crust concerning for secondary impetiginization (figures 2a and 2b), and concomitant non-pitting edema of bilateral feet and lower legs with a positive kaposi-stemmer sign on bilateral 2nd toes. the patient was prescribed doxycycline 100mg twice daily for one month in addition to topical steroids and lower extremity compression and elevation. env is the result of chronic lymphedema that manifests as a nonpitting edema with a papulonodular cobblestone appearance due to excessive accumulation of proteinaceous material in the extracellular matrix. while the most common site for env is in the lower extremities, as they are a gravity-dependent area, env can occur anywhere.2 the diagnosis of env is largely clinical and includes a wide differential diagnosis (e.g. filariasis, pretibial myxedema, lipedema, chromoblastomycosis, lipodermatosclerosis, stewart-treves syndrome, and the more common venous stasis dermatitis). to differentiate env from these other diagnoses, a thorough history and physical exam must be attained.3,4 kaposi-stemmer sign, as demonstrated in both of our patients, is the inability to pinch the dorsal aspect of the skin at the head of the second metatarsal and is indicative of lymphedema.1 many comorbidities put pressure on the lymphatic system and increase lymph capillary permeability. unlike primary lymphedema, which is caused by defects in the lymphatic system, secondary lymphedema is more common and is the discussion a b b a skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 615 result of a separate primary disease process including infectious (e.g. filariasis, especially in developing countries) and noninfectious etiologies (e.g. malignancy).5,6 chronic uncontrolled heart failure, obesity, and hypothyroidism are also common risk factors for secondary lymphedema, with chf (affecting > 2% of the us population) and obesity (affecting ~25% of the us population) being the most prominent.7,8 timely medical management of these chronic systemic conditions may help prevent the development of env.3,4 as such, it is imperative patients and physicians engage in multidisciplinary care and have open communication with patients’ primary care providers to adequately monitor underlying comorbidities.9 successful treatment of env is also dependent on patient compliance. a multifaceted treatment approach involving compression, diuretics, antibiotics (if there is an infectious component), and possibly systemic retinoids is typically most effective.10 lifestyle changes including increased ambulation, weight loss, and leg elevation (above heart level) prove beneficial as well and are included as first-line therapy.10,11 surgical intervention, e.g. debridement of affected skin, may be considered in recalcitrant cases, but does not correct the underlying cause.10,12 early diagnosis and intervention are key as later stages are more difficult to manage and ultimately reverse. identifying the early signs of lymphedema, such as a pitting edema, may improve patient outcomes and implementing lifestyle modifications (such as compression/elevation of the affected limbs) are essential elements of the treatment plan.13 furthermore, diligent follow-up (within 1 month for management of an infectious component, otherwise at least every 3-6 months) is essential for tracking progression/resolution and ensuring proper management.10 env is a rare complication of very common chronic systemic conditions. adequate management of env requires multi-modal therapy, multidisciplinary care, and cooperative coordination between patient and provider. conflict of interest disclosures: none funding: none corresponding author: graham h. litchman, do, ms 327 beach 19th street far rockaway, ny 11691 email: graham.litchman@gmail.com references: 1. liaw fy, huang cf, wu yc, wu by. elephantiasis nostras verrucosa: swelling with verrucose appearance of lower limbs. can fam physician. 2012;58(10):e551-e553. 2. sarma ps, ghorpade a. elephantiasis nostras verrucosa on the legs and abdomen with morbid obesity in an indian lady. dermatol online j. 2008;14(12):20. 3. sisto, k., khachemoune, a. elephantiasis nostras verrucosa. am j clin dermatol 9, 141–146 (2008). https://doi.org/10.2165/00128071200809030-00001 4. baird d, bode d, akers t, deyoung z. elephantiasis nostras verrucosa (env): a complication of congestive heart failure and obesity. j am board fam med. 2010;23(3):413–7. 5. sisto k, khachemoune a. elephantiasis nostras verrucosa: a review. am j clin dermatol 2008; 9: 141–6. 6. tiwari a, cheng k, button m, myint f, hamilton g. differential diagnosis, investigation, and current treatment of lower limb lymphedema. arch surg 2003; 138: 152. 7. yoho rm, budny am, pea as. elephantiasis nostras verrucosa. j am podiatr med assoc 2006; 96: 442–4. 8. hunt sa, abraham wt, chin mh, et al. 2009 focused update incorporated into the acc/aha 2005 guidelines for the diagnosis and conclusion mailto:graham.litchman@gmail.com skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 616 management of heart failure in adults: a report of the american college of cardiology foundation/american heart association task force on practice guidelines developed in collaboration with the international society for heart and lung transplantation. j am coll cardiol 2009; 53: e1–e90. 9. pérez-rodríguez im, ocampo-garza j, garzachapa ji, ocampo-candiani j. elephantiasis nostras verrucosa as a manifestation of morbid obesity. bmj case rep. 2014;2014:bcr2014207574. published 2014 nov 18. doi:10.1136/bcr-2014-207574 10. boyd j, sloan s, meffert j. elephantiasis nostrum verrucosa of the abdomen: clinical results with tazarotene. j drugs dermatol 2004; 3: 446–8. 11. chiang yy, cheng kl, lee wr, hu ch. elephantiasis nostras verrucosa—a case report of effective management with complete decongestive therapy. dermatol sinica. 2005;23(4):228–32. 12. iwao f, sato-matsumura kc, sawamura d, shimizu h. elephantiasis nostras verrucosa successfully treated by surgical debridement. dermatol surg 2004;30:939-41. 13. ito k, inada a, nishikawa m, inoue t. a case of progressive elephantiasis nostras verrucosa. intern med. 2015;54(7):863-864. doi:10.2169/internalmedicine.54.3829 powerpoint presentation 1therapeutics clinical research, san diego, ca; 2biopharmx, inc., menlo park, ca; 3jdr dermatology research, llc, las vegas, nv; 4the acne treatment and research center, morristown, nj poster presented at the 13th winter clinical dermatology conference; maui, hawaii; january 12th-17th, 2018. bhatia n1; ahmadyar m1; hansra h2; del rosso j3; baldwin h4; daniels am2 early onset of efficacy using a 1% and 2% topical minocycline gel for the treatment of rosacea: a small open label study + subject-rated tolerance score scale results: rapid and effective in conclusion, the rapid rate of improvement has the potential to improve treatment compliance and improved patient satisfaction. an important advantage of the topical minocycline formulation – especially in chronic conditions such as rosacea in which long-term use is possible – may be in reduction of risks associated with systemic exposure to this antibiotic. introduction this is the first report of successful treatment of rosacea with a novel topical minocycline gel. the efficacy endpoints of reduction in number and severity of facial lesions were met and showed rapid onset. for both the 1% and 2% formulations, clinically meaningful improvements were reported after just four weeks of treatment. additionally, the minocycline gel treatment had a good profile for safety and tolerability. the majority of subjects stated they would use the minocycline gel again. the study’s small size and open-label single-center design must limit conclusions drawn but suggest that larger-scale testing is warranted. next-phase clinical trials are planned. methods this was a phase 2 open-label feasibility study of 1% and 2% formulations of a novel topical minocycline gel for the treatment of rosacea. rosacea is a common, chronic, and relapsing skin disorder that presents with a variety of clinical manifestations primarily on the central face1. the papulopustular subtype forms acne-like inflammatory papules, pustules, and plaques. genetic, immune, inflammatory, vascular, and environmental mechanisms may contribute to its development2,3. because no cure has been identified, current treatments are generally used chronically or intermittently and aim to suppress its symptoms4. minocycline is effective as a first-line systemic therapy for rosacea; it is thought that, like other tetracyclines, its antiinflammatory properties are responsible5. however, significant side effects such as gastrointestinal distress and vertigo may make long-term use of oral minocycline intolerable and chronic use may contribute to resistance. another form of delivery with lower overall dosage and reduced systemic side effects is needed. the study medication is the first completely solubilized minocycline gel for topical use. its preliminary safety and efficacy profiles have been demonstrated in extensive preclinical testing. additionally, it has completed phase 2a and 2b testing for the treatment of acne vulgaris. 1. webster gf. rosacea. med clin north am 2009; 93:1183. 2. abram k, silm h, maaroos hi, oona m. risk factors associated with rosacea. j eur acad dermatol venereol 2010; 24:565. 3. wilkin j, dahl m, detmar m, drake l, feinstein a, odom r, powell f. standard classification of rosacea: report of the national rosacea society expert committee on the classification and staging of rosacea. j amer acad derm 2002; 46(4):584. 4. maier le. management of rosacea. uptodate january 2017. 5. korting hc, schollmann c. tetracycline actions relevant to rosacea treatment. skin pharmacol physiol 2009; 22:287. at baseline, the 1% group had 24.0 (±13.8; sd) lesions. at week 12, this reduced to 1.7 (±2.9). in the 2% group, the mean of 28.1 (±12.8) to 4.0 (±5.4). percentage of subjects with improvements or no change in investigatorand subject-rated cutaneous tolerance scores from baseline to week 12 cutaneous tolerability ratings are favorable » open-label, single-site study » 20 adults with moderate-to-severe (grade 3 or 4; iga*) papulopustular rosacea » 12 weeks of treatment evaluating 2 arms: 1% (n=10) and 2% (n=9 [10 enrolled, 1 withdrawn]) formulations of topical minocycline gel » treatment assignment was non-randomized » 2-grade reduction in iga to clear or almost clear (0 or 1) from baseline to 12 weeks » change in lesion count from baseline to 12 weeks e f f ic a c y e n d p o in t s s t u d y d e s ig n » cutaneous tolerability (4-point severity scales, investigatorand subject-reported) » hematology & chemistry lab tests » treatment emergent aes * investigator global assessment (iga); based on scale of 0 (clear) to 4 (severe)s a f e t y & t o l e r a b il it y e n d p o in t s sponsored and supported by biopharmx corporation (menlo park, ca). the topical minocycline gel is limited by federal or us law to investigational use only. percentage of subjects with improvements or no change in investigatorand subject-rated cutaneous tolerance scores from baseline to week 12 1%topical minocycline gel (n=10) 2% topical minocycline gel (n=9) combined treatment groups (n=19) investigator-reported erythema 100.0% 100.0% 100.0% scaling/peeling 100.0% 100.0% 100.0% edema 100.0% 100.0% 100.0% subject-reported burning 80.0% 77.8% 78.9% stinging 60.0% 77.8% 68.4% tightness 60.0% 77.8% 68.4% itching 70.0% 88.9% 78.9% topical minocycline gelthe study medication: strong efficacy » stabilizes & solubilizes minocycline » delivered directly to affected facial skin » targeted penetration strong safety profile » low dose: 1% and 2% minocycline » minimizes side effects » low systemic exposure » rapidly absorbing » non-staining » non-oily » non-fluorescing » very high patient satisfaction in clinical trials positive patient experience percentage of subjects with improvements or no change in investigatorand subject-rated cutaneous tolerance scores from baseline to week 12 satisfaction: both 1% and 2% formulations show potential for high patient compliance 1 2 3 4 5 (most favorable) do you like the study medication? scale of 1 5 63% of subjects liked the study medication (with a score of 4 or 5) 79% of subjects would use again good safety profile » generally safe and well tolerated » no serious drug-related adverse events » 3 adverse events were reported, but none were related to the study drug or study assessments » lower molar abscess (n=1; 1% arm) » upper respiratory infection (n=1; 1% arm) » contusion on nose (n=1; 2% arm) » no clinically significant laboratory test findings were noted -100% -80% -60% -40% -20% 0% baseline week 4 week 8 week 12 series1 series2 -100% -80% -60% -40% -20% 0% baseline week 4 week 8 week 12 series1 series2 1%; n=10 2%; n=9 p e rc e n ta g e r e d u c ti o n i n a v e ra g e n u m b e r o f le s io n s p e rc e n ta g e r e d u c ti o n i n a v e ra g e s e v e ri ty o f le s io n s (0 -4 i g a s c a le ) 1%; n=10 2%; n=9 baseline week 4 week 8 week 12 1% 24.0 4.3 3.2 1.7 2% 28.1 11.9 6.6 4.0 percentage change from baseline mean numbers of lesions baseline week 4 week 8 week 12 1% 3.3 1.7 1.3 0.5 2% 3.4 1.9 1.3 0.8 mean iga scores percentage change from baseline reduction in number of lesions reduction in severity of lesions skin july 2019 volume 3 issue 4 copyright 2019 the national society for cutaneous medicine 271 brief articles a case of cutaneous metastatic adenosquamous carcinoma of the cervix taylor novice, bs,1 david oberlin, md,2 and chauncey mchargue, md2 1university of michigan school of medicine, ann arbor, mi 2department of dermatology, henry ford hospital, detroit, mi cervical cancer is the most common gynecologic cancer among women worldwide, and the third most common in the united states.1 histologically, cervical cancer is divided into 4 major histologic subtypes: squamous cell carcinoma, adenocarcinoma, undifferentiated and adenosquamous carcinoma.1,2 cutaneous metastasis is very rare among all subtypes with a reported incidence of 0.1% to 2%; of note, the adenosquamous carcinoma subtype has been reported the least.3-5 we present a case report of ulceronodular cutaneous metastasis of adenosquamous carcinoma of the cervix. a 50-year-old african american female with an 11-year history of metastatic adenosquamous carcinoma of the cervix presented to the emergency department with a new onset asymptomatic rash in her groin of approximately one-month duration (figure 1). the lesions started on her mons pubis and subsequently spread throughout her groin in the coming weeks. she did not try any cutaneous metastases of cervical cancer are very rare among all subtypes with a reported incidence of 0.1 to 2%. a 50-year-old african american female with an eleven-year history of metastatic adenosquamous carcinoma of the cervix presented to the emergency department with a new onset asymptomatic rash in her groin for approximately one-month duration. on physical exam, there were numerous hyperpigmented to violaceous papulonodules across the mons pubis and three ulcerated plaques of the left mons pubis. punch biopsy was consistent with metastases of adenosquamous carcinoma of the cervix. no disease specific interventions were taken and comfort measures were initiated, and the patient passed away five weeks later. to our knowledge, there have only been few reports of cutaneous metastases of adenosquamous carcinoma of the cervix. our patient developed cutaneous metastases eleven years after her diagnosis, which is to our knowledge the longest reported interval from initial diagnosis to development of cutaneous metastases. although rare, it is important to recognize cutaneous metastases of adenosquamous carcinoma of the cervix as it predicts a poor prognosis and treatment has not been shown to improve outcomes. introduction case presentation abstract skin july 2019 volume 3 issue 4 copyright 2019 the national society for cutaneous medicine 272 figure 1: grouped violaceous papulonodules and three ulcerated plaques scattered throughout the mons pubis and groin. figure 2: a punch biopsy with h&e demonstrating atypical, pleomorphic basaloid cells forming nests and cords in the dermis within a fibromucinous stroma. treatment and had no history of similar cutaneous findings in the past. of note, she was initially diagnosed with welldifferentiated adenocarcinoma of the cervix in 2006, but declined treatment with radical hysterectomy. in 2014, she presented with recurrent vaginal bleeding and was subsequently diagnosed with metastatic adenocarcinoma of cervix to local lymph nodes. she underwent 7 weeks of radiotherapy with weekly cisplatin infusion, but her disease continued to spread to her lungs and proximal right tibia. subsequently, in 2016 she completed 15 cycles of a phase 1 trial of pemprolizumab, which was discontinued due to disease progression. upon presentation to our emergency department in december 2017, she reported shortness of breath, pleuritic chest pain and this new onset rash. she had not been on treatment for her metastatic adenosquamous carcinoma of the cervix for over 1 year. on examination, there were numerous hyperpigmented to violaceous papulonodules across the mons pubis and 3 ulcerated plaques of the left mons pubis. a 4mm punch biopsy of a plaque was performed with histopathology demonstrating a dermal infiltrate of atypical, pleomorphic basaloid cells forming nests and cords within a fibromucinous stroma (fig 2). immunohistochemical staining was strong and uniformly positive for ck7, with rare focally positive cells for p63 and negative ck20. these findings were consistent with cutaneous metastasis from adenosquamous carcinoma of the cervix. she declined any additional treatments and passed away approximately 5 weeks later of respiratory failure secondary to sepsis and disease progression. cervical cancer is the most common gynecologic cancer among women worldwide. the most common sites of metastasis include lymph nodes then liver, lung, and bone.2 cervical cancer rarely metastasizes to the skin, with a reported incidence of 0.1% to 2%. the most common locations of cutaneous metastases include abdominal wall, anterior chest wall and vulva. on examination, cervical cancer cutaneous metastases typically present as nodules, plaques and inflammatory telangiectasias. ulcerations are uncommon; however, our patient presented with ulcerated plaques in addition to multiple nodules.1,4-6 histopathologically, adenosquamous carcinoma metastases demonstrate a biphasic pattern of well-defined malignant discussion skin july 2019 volume 3 issue 4 copyright 2019 the national society for cutaneous medicine 273 glandular and squamous features. special stains may aid in diagnosis, including p63 for the squamous component and ck7+/ck20 for both cervical squamous cell carcinoma and adenocarcinoma components.7,8 among the subtypes of cervical cancer, metastasis to the skin from adenosquamous carcinoma of the cervix has been reported the least. in a review of 1185 cases of cervical cancer, imachi et. al found that only 15 cases spread cutaneously, none of which were adenosquamous carcinoma.5 similarly, agrawal et. al found that adenosquamous carcinoma of the cervix was the least likely to metastasize to the skin; of the 47 metastases, 30 (63.8%) were squamous cell carcinoma, followed by 5 (10.6%) adenocarcinoma, 2 (4.2%) poorly differentiated or undifferentiated, 1 (2.1%) mixed adenosquamous carcinoma (2.1%), and in 9 cases (19.1%) histopathology was not reported.6 to our knowledge, only 2 cases of adenosquamous carcinoma of the cervix spreading to the skin have been described in the literature. in 1966, reingold added an addendum to his review of metastases from internal carcinoma to include a 43-year-old female who had metastases of adenosquamous carcinoma to the thighs and lower abdomen.3 in 2010, fumerton et al presented the first case report of adenosquamous carcinoma metastasizing to the lower abdomen, hips, and groin in a 32year-old women who passed away within 3 months of the cutaneous lesions appearing.4 irrespective of histologic subtype, cutaneous metastases of cervical carcinoma predict a poor prognosis, as this usually occurs with local or regional recurrence.4,5,9,10 the incidence of skin metastasis increases with an increasing initial tumor stage, with an incidence of 0.8% in stage i and 4.8% in stage iv.5 cutaneous metastases typically present a year after the diagnosis of cervical cancer, although they may develop up to 10 years after the initial diagnosis.1 treatment options tried include radiation, chemotherapy, and surgery; however, the average length of survival after cutaneous metastases develop is 3 months.6 imachi et al found that only 20% of patients survived 1 year after the development of metastases to the skin.5 our patient presented with nodules and ulcerative plaques on her mons pubis and groin with a biopsy supporting metastatic adenosquamous carcinoma of the cervix. ulcerative plaques have not commonly been described as a morphologic subtype of cervical adenosquamous carcinoma metastases. in addition, her histologic subtype of adenosquamous is the least common variant to spread to the skin.5,6 stains such as ck7, cd20 and p63 may aid pathological diagnosis. she developed cutaneous metastases 11 years after her diagnosis, which is to our knowledge the longest reported interval from initial diagnosis to development of cutaneous metastases to date. unfortunately, she passed away form her condition approximately 5 weeks after developing the cutaneous lesions, supporting the literature that cutaneous metastasis of cervical carcinoma portends a poor prognosis3,5,6,9,10 although rare, it is important to recognize cutaneous metastases of adenosquamous carcinoma of the cervix as it predicts a poor prognosis and treatment has not been shown to improve outcome conflict of interest disclosures: none. funding: none. corresponding author: taylor novice, b.s. university of michigan school of medicine ann arbor, mi tnovice@med.umich.edu skin july 2019 volume 3 issue 4 copyright 2019 the national society for cutaneous medicine 274 references: 1. benoulaid m, elkacemi h, bourhafour i, et al. skin metastases of cervical cancer: two case reports and review of the literature. journal of medical case reports. 2016;10(1):265. 2. seamon lg, java jj, monk bj, et al. impact of tumour histology on survival in advanced cervical carcinoma: an nrg oncology/gynaecologic oncology group study. british journal of cancer. 2017;118:162. 3. reingold im. cutaneous metastases from internal carcinoma. cancer. 1966;19(2):162-168. 4. fumerton r, afifi t, martinka m, de gannes g. cutaneous metastases of cervical adenosquamous carcinoma. journal of the american academy of dermatology. 2010;63(2):e48-e49. 5. imachi m, tsukamoto n, kinoshita s, nakano h. skin metastasis from carcinoma of the uterine cervix. gynecologic oncology. 1993;48(3):349354. 6. agrawal a, yau a, magliocco a, chu p. cutaneous metastatic disease in cervical cancer: a case report. journal of obstetrics and gynaecology canada. 2010;32(5):467-472. 7. chu p, wu e, weiss lm. cytokeratin 7 and cytokeratin 20 expression in epithelial neoplasms: a survey of 435 cases. modern pathology : an official journal of the united states and canadian academy of pathology, inc. 2000;13(9):962-972. 8. wang ty, chen bf, yang yc, et al. histologic and immunophenotypic classification of cervical carcinomas by expression of the p53 homologue p63: a study of 250 cases. human pathology. 2001;32(5):479-486. 9. chen c-h, chao k-c, wang p-h. advanced cervical squamous cell carcinoma with skin metastasis. taiwanese journal of obstetrics and gynecology. 2007;46(3):264-266. 10. farley jh, hickey kw, carlson jw, rose gs, kost er, harrison ta. adenosquamous histology predicts a poor outcome for patients with advanced-stage, but not early-stage, cervical carcinoma. cancer. 2003;97(9):2196-2202. skin december 2018 volume 2 supplemental issue copyright 2018 the national society for cutaneous medicine 109 rising derm stars non-invasive buccal swab gene testing for skin cancer risk lauren moy, md1 1department of dermatology, loyola university, chicago, il background: the awareness of skin cancer is increasing, and there are new commercial kits on the market which advertise the ability to provide a patient with a skin cancer risk profile. these tests are based on research findings that individual single nucleotide polymorphisms (snps) are associated with increased risk of melanoma and nonmelanoma skin cancer (nmsc). however, to our knowledge, there is no current study in the literature that examines the prevalence of an extended set of identified snps within the skin cancer and environmental control patient population. in this pilot study, we aimed to examine whether previously identified melanoma and non-melanoma associated snps which were found to be present in a relatively heterogeneous population with a history of skin cancer versus an age and environmental matched controls. the undertaking of this project serves to further the current understanding of the genetic profile for those at higher risk for developing skin cancer. methods: patients with biopsy-proven nmsc were recruited from a private mohs micrographic surgical practice in southern california. nineteen nmsc patients and their age-matched and environmental control spouses underwent genotyping of 7 previously discovered snps associated with melanoma and nmsc via buccal swabs. results: in a random, heterogeneous population in southern california, snp’s chr1, pad16, pigu, tdg had a similar association with nmsc previously reported in prior studies. due to small trial size, no conclusions or observable associations could be drawn from the snps mc1r, tp53, and xrcc1. conclusion: this data supports that 4 of the 7 snp’s studied had similar associations and could be a predictive tool of nmsc risk. the remaining three snp’s did not have a definitive association with malignancy. previous trials predominantly studied more homogeneous patient populations (icelandic, english) or people who lived in locations with more inclement weather. a better understanding of the genetic contributions that can affect dna damage will help to prevent dna damage and target with precision medicine dna repair therapeutics in the future. larger studies are needed to further elucidate the specific roles of these snps collectively and ultimately to develop a genetic profile and prevention techniques for those patients at increased risk of developing skin cancer. poster presented at 13th annual winter clinical dermatology conference; january 12–17, 2018; maui, hi certolizumab pegol for the treatment of patients with moderate-to-severe chronic plaque psoriasis: an overview of 3 randomized controlled trials andrew blauvelt,1 kristian reich,2 mark lebwohl,3 daniel burge,4 catherine arendt,5 luke peterson,6 robert rolleri,6 alice gottlieb7 1oregon medical research center, portland, or; 2dermatologikum hamburg and sciderm research institute, hamburg, germany; 3icahn school of medicine at mount sinai, new york, ny; 4dermira, inc., menlo park, ca; 5ucb pharma, brussels, belgium; 6ucb pharma, raleigh, nc; 7new york medical college at metropolitan hosptial, new york, ny introduction • certolizumab pegol (czp), the only fc-free, pegylated, anti-tnf biologic, has demonstrated promising results in three ongoing, phase 3, randomized, double-blind, placebo-controlled clinical trials in adults with moderate-to-severe chronic plaque psoriasis (cimpasi-1,1,2 cimpasi-2,1,2 and cimpact3,4) • czp does not bind the neonatal fc receptor for igg (fcrn) and consequently shows minimal placental transfer from mothers to infants5 • czp is approved for the treatment of adults with rheumatoid arthritis, psoriatic arthritis, crohn’s disease (us only), ankylosing spondylitis, and axial spondyloarthritis (eu only) • pooled efficacy and safety results from the first 16 weeks of three 144-week multinational, randomized, double-blind clinical trials evaluating czp versus placebo are reported here methods study design • cimpasi-1 (nct02326298), cimpasi-2 (nct02326272), and cimpact (nct02346240) are ongoing phase 3, multicenter, double-blind, placebo-controlled (and active-controlled; cimpact only) trials • patients were randomized to czp 400 mg every 2 weeks (q2w), czp 200 mg q2w (following 400 mg loading doses at weeks 0, 2, and 4), or placebo q2w for 16 weeks (or etanercept [etn] twice weekly for 12 weeks in cimpact only; etn data are not included in this pooled analysis) (figure 1) figure 1. study design etn 50 mg bw (n=170) washout czp 200 mg q2w (n=165)ld czp 400 mg q2w (n=167) placebo q2w (n=57) 2:2:1 randomization cimpasi-1 | cimpasi-2 n=234 | 227 double-blind maintenance period open-label treatment • long-term therapy • czp-treated responders (pasi 50) continued on the same dose 3:3:3:1 randomization n=559 double-blind maintenance period open-label treatment • long-term therapy • czpand etn-treated responders (pasi 75) re-randomized to czp or placebo cimpasi-1 & cimpasi-2 cimpact 0week 16a,b 48 144 coprimary endpoints pasi 75 and pga 0/1 czp 200 mg q2w (n=95 | 91) czp 400 mg q2w (n=88 | 87) placebo q2w (n=51 | 49) ld 0week 16c 48 14412 primary endpoint pasi 75 ain cimpasi-1 and cimpasi-2, pasi 50 nonresponders at week 16 entered the escape arm for treatment with open-label czp 400 mg q2w bupon entering the maintenance period, placebo-treated pasi 75 responders (≥75% reduction in pasi) continued blinded placebo treatment and placebo-treated pasi 50-74 responders (≥50% but <75% reduction in pasi) received czp 400 mg loading dose at weeks 16, 18, and 20 and then czp 200 mg q2w cin cimpact, pasi 75 nonresponders at week 16 entered the escape arm for treatment with open-label czp 400 mg q2w bw, twice weekly; czp, certolizumab pegol; etn, etanercept; ld, czp 400 mg loading dose at weeks 0, 2, and 4; pasi 50, ≥50% reduction in psoriasis area and severity index (pasi); pasi 75, ≥75% reduction in pasi; pga 0/1, ‘clear’/‘almost clear’ with ≥2 category improvement in physician’s global assessment; q2w, every 2 weeks patients • eligible patients were ≥18 years of age with moderate-to-severe chronic psoriasis for ≥6 months (psoriasis area severity index [pasi] ≥12, body surface area affected [bsa] ≥10%, and physician’s global assessment [pga] ≥3 on a 5-point scale) and candidates for systemic psoriasis therapy, phototherapy, and/or photochemotherapy • patients were excluded if they had previous treatment with czp (or etn in cimpact) or >2 biologics (including anti-tnf); had a history of primary failure to any biologic or secondary failure to >1 biologic; or had erythrodermic, guttate, or generalized pustular forms of psoriasis study assessments • coprimary endpoints for the pooled analysis were pasi 75 (≥75% reduction in pasi) and pga 0/1 (’clear’/’almost clear’ with ≥2-category improvement) responder rates at week 16; pasi 90 (≥90% reduction in pasi) responder rate at week 16 was a key secondary endpoint; dermatology life quality index (dlqi) 0/1 responder rate and change from baseline (cfb) in dlqi versus placebo at week 16 were also assessed • safety evaluation included assessment of treatment-emergent adverse events (teaes) statistical analyses • pasi 75, pga 0/1, and pasi 90 responder rates were analyzed via a logistic regression model with treatment group, region, study, prior biologic exposure (yes/no), and the interactions study*region and study*prior biologic exposure (yes/ no) as factors using markov chain monte carlo methodology for multiple imputation to address missing data • cfb in dlqi scores are adjusted least squares mean differences from an analysis of covariance (ancova) model with treatment group, region, study, prior biologic exposure (yes/no), and the interactions study*region and study*prior biologic exposure (yes/no) as factors and baseline dlqi score as a covariate using last observation carried forward (locf) imputation • dlqi 0/1 responder rates were summarized descriptively with counts and percentages, where missing data were imputed using nonresponder imputation (nri) • p-values were not adjusted for multiplicity results disposition, demographics, and baseline disease characteristics • of 850 patients randomized to czp or placebo in cimpasi-1, cimpasi-2, or cimpact, 815 patients (95.9%) completed 16 weeks of treatment (333 [97.4%] for czp 400 mg q2w, 336 [95.7%] for czp 200 mg q2w, and 146 [93.0%] for placebo; figure 2) • patient demographics and baseline disease characteristics were similar between treatment groups (table 1) and across trials (data not shown) including baseline pasi and pga scores • across the overall population, approximately one-third of study participants reported prior biologic use (table 1) figure 2. patient disposition (week 16) completed week 16 placebo n=157 n=146 (93.0%) n=336 (95.7%) n=333 (97.4%) czp 200 mg q2wb n=351 randomized n=850a screened n=1320 czp 400 mg q2w n=342 discontinued lack of e�cacy lost to follow-up consent withdrawn 11 (7.0%) 1 (0.6%) 3 (1.9%) 7 (4.5%) discontinued adverse event lost to follow-up consent withdrawn other 15 (4.3%) 3 (0.9%) 4 (1.1%) 7 (2.0%) 1 (0.3%) discontinued lack of e�cacy lost to follow-up consent withdrawn other 9 (2.6%) 2 (0.6%) 2 (0.6%) 2 (0.6%) 3 (0.9%) aan additional 170 patients in cimpact were randomized to etn and are not included in these pooled results bczp 200 mg q2w patients received loading dose of czp 400 mg at weeks 0, 2, and 4 czp, certolizumab pegol; etn, etanercept; q2w, every two weeks table 1. patient demographics and baseline disease characteristics placebo (n=157) czp 200 mg q2wc (n=351) czp 400 mg q2w (n=342) demographics age (years), mean ± sd 46.0 ± 13.3 46.1 ± 13.4 45.2 ± 12.6 male, n (%) 95 (60.5) 238 (67.8) 210 (61.4) white, n (%) 146 (93.0) 331 (94.3) 322 (94.2) geographic region, n (%) north america europe   71 (45.2) 86 (54.8)   136 (38.7) 215 (61.3)   133 (38.9) 209 (61.1) weight (kg), mean ± sd 92.2 ± 25.8 92.6 ± 22.3 89.2 ± 22.7 bmi (kg/m2), mean ± sd 31.2 ± 7.8 31.0 ± 7.1 30.1 ± 7.1 baseline disease characteristics duration of psoriasis at screening (years), mean ± sd 17.7 ± 12.7 18.5 ± 13.1 18.2 ± 12.0 concurrent psoriatic arthritis (selfreported), n (%) 25 (15.9) 59 (16.8) 65 (19.0) pasi, mean ± sd 18.8 ± 6.8 20.3 ± 8.1 20.2 ± 7.5 dlqi,a mean ± sd 13.4 ± 7.7 13.6 ± 7.2 14.5 ± 7.1 bsa (%), mean ± sd 23.5 ± 13.6 25.6 ± 15.9 25.5 ± 14.9 pga, n (%) 3: moderate 4: severe 112 (71.3) 45 (28.7) 242 (68.9) 109 (31.1) 239 (69.9) 103 (30.1) any prior systemic psoriasis treatment, n (%) 111 (70.7) 249 (70.9) 247 (72.2) prior biologic use,b n (%) anti-tnf anti-il17 40 (25.5) 24 (15.3) 13 (8.3) 106 (30.2) 49 (14.0) 54 (15.4) 107 (31.3) 43 (12.6) 43 (12.6) afor dlqi: placebo, n=154; czp 200 mg q2w, n=346; czp 400 mg q2w, n=340 bpatients may have had exposure to >1 prior biologic but ≤2 per exclusion criteria; 1 patient in the czp 400 mg q2w group in cimpasi-2 had prior exposure to 3 biologics, which was a protocol violation cczp 200 mg q2w patients received loading dose of czp 400 mg at weeks 0, 2, and 4 bmi, body mass index; bsa, body surface area; czp, certolizumab pegol; dlqi, dermatology life quality index; il, interleukin; pasi, psoriasis area and severity index; pga, physician’s global assessment; q2w, every 2 weeks; tnf, tumor necrosis factor pooled efficacy • at week 16, pasi 75 and pga 0/1 responder rates were significantly greater in the pooled czp 400 mg q2w and pooled czp 200 mg q2w groups versus placebo, with clinically meaningful differences observed as early as week 4 for both czp doses versus placebo (figure 3 and figure 4) • similarly, week 16 pasi 90 responder rates were significantly greater in the czp 400 mg q2w and czp 200 mg q2w groups versus placebo, with clinically meaningful differences observed as early as week 8 for both czp doses versus placebo (figure 5) • meaningful improvements in quality of life, measured by cfb in dlqi and dlqi 0/1 responder rates, were observed in czp-treated patients versus placebo at week 16 (figure 6) figure 3. pooled pasi 75 responder rates from baseline to week 16 r e sp o n d e r r a te ( % ) week 100 80 60 20 40 0 0 2 4 8 12 16 placebo (n=157) czp 200 mg q2w (n=351) czp 400 mg q2w (n=342) 0% 1.6% 3.9% 7.4% 7.5% 2.3% 19.4% 52.8% 68.9% 74.5% 2.6% 16.5% 52.8% 73.0% 80.1% czp loading dosea 74.5% 80.1% **p<0.0001 versus placebo (not adjusted for multiplicity) aczp 200 mg q2w patients received loading dose of czp 400 mg at weeks 0, 2, and 4 responder rates are the adjusted predicted probabilities based on logistic regression model with factors for treatment, region, study, prior biologic exposure (yes/no), and the interactions study*region and study*prior biologic exposure (yes/no) where missing data were imputed using multiple imputation (mcmc method) czp, certolizumab pegol; ld, loading dose of czp 400 mg q2w at weeks 0, 2, and 4; mcmc, markov chain monte carlo; pasi 75, ≥75% reduction in psoriasis area and severity index; q2w, every 2 weeks figure 4. pooled pga 0/1 responder rates from baseline to week 16 r e sp o n d e r r a te ( % ) week 100 80 60 20 40 0 0 2 4 8 12 16 placebo (n=157) czp 200 mg q2w (n=351) czp 400 mg q2w (n=342) 0.4% 0.5% 4.7% 3.9% 2.8% 1.9% 13.0% 38.0% 48.2% 54.6% 1.7% 12.3% 39.7% 55.4% 63.7% czp loading dosea 54.6% 63.7% *p<0.05, **p<0.0001 versus placebo (not adjusted for multiplicity) aczp 200 mg q2w patients received loading dose of czp 400 mg at weeks 0, 2, and 4 responder rates are the adjusted predicted probabilities based on logistic regression model with factors for treatment, region, study, prior biologic exposure (yes/no), and the interactions study*region and study*prior biologic exposure (yes/no) where missing data were imputed using multiple imputation (mcmc method) czp, certolizumab pegol; mcmc, markov chain monte carlo; pga 0/1, ‘clear’/‘almost clear’ with ≥2-category improvement in physician’s global assessment; q2w, every 2 weeks figure 5. pooled pasi 90 responder rates from baseline to week 16 r e sp o n d e r r a te ( % ) week 100 80 60 20 40 0 0 2 4 8 12 16 placebo (n=157) czp 200 mg q2w (n=351) czp 400 mg q2w (n=342) 0% 0.8% 0.5% 1.7% 1.6% 0.9% 4.3% 21.0% 32.7% 44.5% 0.6% 3.4% 19.3% 37.4% 52.2% czp loading dosea 44.5% 52.2% *p<0.05, **p<0.0001 versus placebo (not adjusted for multiplicity) aczp 200 mg q2w patients received loading dose of czp 400 mg at weeks 0, 2, and 4 responder rates are the adjusted predicted probabilities based on logistic regression model with factors for treatment, region, study, prior biologic exposure (yes/no), and the interactions study*region and study*prior biologic exposure (yes/no) where missing data were imputed using multiple imputation (mcmc method) czp, certolizumab pegol; mcmc, markov chain monte carlo; pasi 90, ≥90% reduction in psoriasis area and severity index; q2w, every 2 weeks figure 6. pooled dlqi scores at baseline and week 16 and dlqi 0/1 responder rates at week 16 mean cfb: -2.4 11.0 13.4 placebo (n=154) -9.1** 4.5 13.6 czp 200 mg q2wa (n=347) -10.4** 4.1 14.5 czp 400 mg q2w (n=340) 8.3 placebo (n=157) 42.7 czp 200 mg q2wa (n=351) 47.1 czp 400 mg q2w (n=342) m e a n s c o re 20 15 10 5 0 a. dlqi mean scores and cfb bl wk 16 r e sp o n d e r r a te ( % ) 100 80 60 40 20 0 b. dlqi 0/1 responder rates **p<0.0001 vs placebo based on adjusted least squares mean difference from an ancova model with treatment group, region, study, prior biologic exposure (yes/no), and the interactions study*region and study*prior biologic exposure (yes/no) as factors and baseline dlqi score as a covariate using locf imputation (p-values not adjusted for multiplicity); for dlqi 0/1 responder rates, missing data imputed based on nri method (p-values not calculated) aczp 200 mg q2w patients received loading dose of czp 400 mg at weeks 0, 2, and 4 bl, baseline; cfb, change from bl; czp, certolizumab pegol; dlqi, dermatology life quality index; locf, last observation carried forward; nri, nonresponder imputation; q2w, every 2 weeks pooled safety • the safety profile for both czp doses was consistent with the anti-tnf class in psoriasis; based on the known safety profile of czp,6 no new safety signals were observed (table 2) – the incidence of teaes was generally similar between czp 400 mg q2w and placebo groups, and was lower in the czp 200 mg q2w group versus placebo; teaes infrequently led to discontinuation • serious teaes and serious infections and infestations were infrequent across treatment groups (czp 400 mg q2w: 4.7% and 0.6%, respectively; czp 200 mg q2w: 1.4% and 0%; placebo: 4.5% and 0%) (table 2) – two serious infections were reported in the czp 400 mg q2w group – hematoma infection and abdominal abscess in 1 patient following a bicycle accident, and pneumonia in 1 patient • no deaths were reported in any of the three studies through week 16 (table 2) table 2. treatment-emergent adverse events (safety set) placebo (n=157) czp 200 mg q2wa (n=350) czp 400 mg q2w (n=342) teaes, n (%) all 97 (61.8) 197 (56.3) 217 (63.5) serious 7 (4.5) 5 (1.4) 16 (4.7) discontinuations due to teae, n (%) 0 4 (1.1) 4 (1.2) deaths, n (%) 0 0 0 frequent and other teaes of interest, n (%) infections and infestations latent tuberculosis active tuberculosis candida infections oral fungal infection fungal skin infection nasopharyngitis upper respiratory tract infection 53 (33.8) 0 0 0 0 0 19 (12.1) 11 (7.0) 108 (30.9) 0 0 1 (0.3) b 0 0 42 (12.0) 17 (4.9) 124 (36.3) 0 0 0 1 (0.3) 1 (0.3)c 43 (12.6) 23 (6.7) serious infections 0 0 2 (0.6) d non-melanoma skin cancer 0 0 1 (0.3) e malignancy (excluding non-melanoma skin cancer) 0 0 0 depression 0 2 (0.6) 2 (0.6) aczp 200 mg q2w patients received loading dose of czp 400 mg at weeks 0, 2, and 4 bvulvovaginal candidiasis creported as fungal infection preferred term in the database dhematoma infection and abdominal abscess in 1 patient (bicycle accident), and pneumonia in 1 patient ebasal cell carcinoma safety set includes all randomized patients who received ≥1 dose of study medication czp, certolizumab pegol; teae, treatment-emergent adverse event; q2w, every 2 weeks conclusions • in the phase 3 program, certolizumab pegol (czp) 400 mg q2w and czp 200 mg q2w were each associated with statistically significant, clinically meaningful improvements in moderate-to-severe chronic plaque psoriasis – clinically meaningful differences in pasi 75 and pga 0/1 responder rates versus placebo were observed as early as week 4 – greater improvement in quality of life as measured by cfb in dlqi and dlqi 0/1 responder rate was seen for both czp dose groups compared with placebo at week 16 – responder rates were numerically greater for patients treated with czp 400 mg q2w versus 200 mg q2w • in the phase 3 program, the safety profile for czp was consistent with the anti-tnf class in psoriasis; based on the known safety profile of czp, no new safety signals were observed – serious teaes were infrequent across treatment groups references 1. gottlieb et al. oral presentation at: the 75th annual meeting of the american academy of dermatology; march 3-7, 2017; orlando, fl. abstract 5077 2. reich et al. poster presented at the 26th european academy of dermatology and venerology congress; september 13-17, 2017; geneva, switzerland 3. lebwohl et al. poster presentation at: 13th annual maui derm for dermatologists; march 20-24, 2017; maui, hi 4. augustin et al. poster presented at the 26th european academy of dermatology and venerology congress; september 13-17, 2017; geneva, switzerland 5. mariette et al. ann rheum dis. 2017. doi: 10.1136/annrheumdis-2017-212196. [epub ahead of print] 6. cimzia [package insert]. smyrna, ga: ucb, inc; 2016 acknowledgements the studies were funded by dermira, inc.in collaboration with ucb, inc. ucb is the regulatory sponsor of certolizumab pegol in psoriasis. medical writing support for this presentation was provided by prescott medical communications group (chicago, il). all costs associated with the development of this presentation were funded by ucb. author disclosures ab: abbvie; aclaris; allergan; almirall; amgen; boehringer ingelheim; celgene; dermavant; dermira; eli lilly; genentech/roche; gsk; janssen; leo pharma; merck; novartis; pfizer; purdue pharma; regeneron; sandoz; sanofi genzyme; sienna pharmaceuticals; sun pharma; ucb; valeant; vidac. kr: abbvie; amgen; biogen; boehringer ingelheim; celgene; centocor; covagen; eli lilly; forward pharma; gsk; janssen; leo pharma; medac; merck; novartis; ocean pharma; pfizer; regeneron; takeda; ucb; xenoport. ml: abbvie; allergan; amgen; boehringer ingelheim; celgene; eli lilly; janssen; leo pharma; medimmune/astrazeneca; novartis; pfizer; sun pharma; ucb; valeant; vidac. db: employee of dermira. ca, lp, and rr: employees of ucb. abg: abbvie; allergan; beiersdorf; bristol-myers squibb; celgene; dermira; eli lilly; incyte; janssen; novartis; reddy labs; sun pharma; ucb; valeant. integrated safety and efficacy analysis of fmx103 1.5% topical minocycline foam for the treatment of moderate-to-severe papulopustular rosacea: results from two phase 3 studies james q. del rosso, do1; linda stein gold, md2; leon kircik, md3; neal d. bhatia, md4; neil sadick, md5; matthew zirwas, md6; edward lain, md7; iain stuart, phd8 1jdr dermatology research/thomas dermatology, las vegas, nv; 2 henry ford health system, detroit, mi; 3icahn school of medicine at mount sinai, new york, ny; 4therapeutics clinical research, san diego, ca; 5sadick dermatology, new york, ny; 6dermatologists of the central states, columbus, oh; 7sanova dermatology, austin, tx; 8vyne therapeutics inc., bridgewater, nj introduction • rosacea is a common, chronic, inflammatory cutaneous disorder involving the face that affects approximately 16 million individuals in the united states1,2 • rosacea is typically characterized by cutaneous signs such as flushing, erythema, edema, papules, and pustules1-5 • topical therapies such as metronidazole, azelaic acid, and ivermectin are considered first-line therapies for papulopustular rosacea2-5 – oral tetracyclines, specifically doxycycline and minocycline, are mainstays of treatment for moderate-tosevere disease; however, they have the potential for significant systemic side effects2,4 – independent of their antimicrobial activity, tetracyclines may exert beneficial effects in rosacea due, in part, to their anti-inflammatory, antiapoptotic, and antiangiogenic activities6 • fmx103 1.5% is a topical minocycline foam being developed for the treatment of moderate-to-severe papulopustular rosacea7,8 – the efficacy, safety, and tolerability of fmx103 1.5% from two identical, phase 3, randomized, double-blind, vehicle-controlled studies, fx2016-11 (study 11) and fx2016-12 (study 12), have previously been presented8 • objective: to compare integrated efficacy and safety of fmx103 1.5% vs vehicle administered daily for 12 weeks methods • the 2 pivotal phase 3 studies (fx2016-11, study 11; fx2016-12, study 12) were randomized, double-blind comparisons of fmx103 1.5% with vehicle foam (figure 1) • qualified subjects were enrolled and randomly assigned in a 2:1 ratio to receive either fmx103 1.5% or vehicle • subjects applied the assigned study drug once daily for 12 weeks and returned for visits at weeks 2, 4, 8, and 12 • the efficacy data from studies 11 and 12 were pooled for analysis both in totality and for the predefined subgroup of baseline disease severity (moderate, iga=3; severe, iga=4) • safety endpoints included adverse events and local facial tolerability assessments, which were summarized for the overall pooled population, as well as for predefined subgroups including sex, race, age, and baseline disease severity figure 1. study design week 12baseline key inclusion criteria • males and nonpregnant females ≥18 years • moderate-to-severe facial papulopustular rosacea (iga score of 3 or 4) • >15 to ≤75 facial papules and pustules, excluding lesions involving eyes and scalp; ≤2 nodules on the face • presence or history of facial erythema or flushing integrated efficacy populationa (n=1522) vehicle foam (n=513) fmx103 1.5% (n=1009) study 11, n=256 study 12, n=257 study 11, n=495 study 12, n=514 • • co-primary efficacy endpoints absolute change in the inflammatory lesion count at week 12 compared to baseline iga success rate (dichotomized as yes/no) at week 12, where success was defined as an iga score of 0 or 1, and at least a 2-grade improvement (decrease) from baseline week 4 week 8 athe integrated efficacy population consisted of all randomized subjects that were pooled from studies 11 (n=751) and 12 (n=771). one subject was randomized but discontinued prior to taking the first dose and was therefore not included in the integrated safety population. iga, investigator’s global assessment; based upon a 5-point scale with 0=clear, 1=almost clear, 2=mild, 3=moderate, and 4=severe. results baseline demographics and disease characteristics • 1522 subjects were included in the integrated efficacy population • baseline demographics and disease characteristics are shown in table 1 • the majority of subjects were female (70.6%) and white (96.4%). the mean age was 50.0 and ranged from 18-86 years. at baseline, 86.9% and 13.1% of subjects had moderate (iga=3) or severe (iga=4) disease, respectively • baseline demographics and disease characteristics were similar across treatment groups table 1. baseline demographics and disease characteristics variable fmx103 1.5%(n=1009) vehicle foam (n=513) overall (n=1522) mean age (sd) 49.9 (13.84) 50.3 (13.17) 50 (13.61) 18 to 40 years, n (%) 265 (26.3) 118 (23.0) 383 (25.2) 41 to 64 years, n (%) 588 (58.3) 311 (60.6) 899 (59.1) 65 years, n (%) 156 (15.5) 84 (16.4) 240 (15.8) sex, m (%) male 289 (28.6) 159 (31.0) 448 (29.4) female 720 (71.4) 354 (69.0) 1074 (70.6) race white 973 (96.5) 491 (96.1) 1464 (96.4) black 14 (1.4) 5 (1.0) 19 (1.3) other 21 (2.1) 15 (2.9) 36 (2.4) mean inflammatory lesion count, n (sd) 29.2 (12.48) 29.6 (12.57) 29.4 (12.5) iga score, n (%) 3 – moderate 887 (87.9) 435 (84.8) 1322 (86.9) 4 – severe 122 (12.1) 78 (15.2) 200 (13.1) iga, investigator’s global assessment; sd, standard deviation. note that percentages exclude missing values. pooled efficacy data • in the combined analysis of the two pivotal phase 3 studies, fmx103 1.5% demonstrated statistically significant benefit compared to vehicle foam for both co-primary endpoints (figure 2) – at week 12, fmx103 1.5% demonstrated a significantly greater reduction from baseline in inflammatory lesions than vehicle foam (figure 2a) – a significantly greater number of subjects receiving fmx103 1.5% achieved iga treatment success at week 12 than those receiving vehicle foam (figure 2b) figure 2. co-primary efficacy endpoints % ig a s uc ce ss a t w ee k 12 r ed uc tio n fr om b as el in e at w ee k 12 in in fla m m at or y le si on s (l s m ea n) ba -20 -16 -12 -8 -4 -18 -14 -10 -6 0 -2 -18.0 n=1009 fmx103 1.5% -14.9 n=513 vehicle foam p<0.001, lsm diff: 3.0 lsm diff 95% ci: 1.92, 4.16 0 20 40 60 10 30 50 fmx103 1.5% n=1009 50.6% vehicle foam n=513 41.0% p<0.001 rr: 1.24; 95% ci: 1.095, 1.394 iga, investigator’s global assessment; lsm diff, lsmean difference; ci, confidence interval; rr, risk ratio. integrated efficacy population (multiple imputation). • fmx103 1.5% demonstrated a statistically significant advantage over vehicle foam for inflammatory lesions beginning as early as week 4 (figure 3) – the fmx103 1.5% group exhibited a significantly greater reduction in inflammatory lesions at week 4 than the vehicle foam group – this statistically significant advantage over vehicle was maintained at weeks 8 and 12 figure 3. change from baseline in inflammatory lesion counts by visit r ed u ct io n f ro m b as el in e at w ee k 12 in in fl am m at o ry le si o n s (l s m d if f) -25 -20 -15 -10 -5 0 0 4 8 12 fmx103 1.5% n=1009 vehicle foam, n=513 week integrated efficacy population (multiple imputation); lsm diff, least squares mean difference • fmx103 1.5% demonstrated a statistically significant advantage over vehicle foam for iga treatment success beginning as early as week 4 (figure 4) – this statistical advantage over vehicle was maintained throughout the study, with approximately half of the subjects in the fmx103 1.5% group achieving treatment success by week 12 figure 4. iga treatment success over time % ig a tr ea tm en t s uc ce ss 0 50 25 75 week 4 128 fmx103 1.5% (n=1009) vehicle foam (n=513) 16.0 9.4 37.8 30.0 50.6 41.0 p=0.001 p=0.003 p<0.001 iga, investigator’s global assessment; integrated efficacy population (multiple imputation); p values are based on common risk ratios. efficacy results in the patient subgroups scored as moderate or severe at baseline • fmx103 1.5% demonstrated statistically significant advantages over vehicle foam in both baseline disease severity subgroups (figure 5) – in both moderate (iga=3) and severe (iga=4) subpopulations, the change from baseline at week 12 in inflammatory lesions was significantly greater in the fmx103 1.5% group than in the vehicle foam group (figure 5a) – similarly, a significantly greater number of subjects in the fmx103 1.5% group achieved iga treatment success by week 12 than in the vehicle foam group, regardless of baseline disease severity (figure 5b) – the treatment effect for fmx103 1.5% vs vehicle foam was more pronounced in the severe subgroup than in the moderate subgroup for both inflammatory lesions (figure 5a) and iga treatment success (figure 5b) figure 5. efficacy of fmx103 1.5% across baseline disease severities r ed uc tio n fr om b as el in e at w ee k 12 in in fla m m at or y le si on s (l s m ea n) a -30 -20 -10 -25 -15 0 -5 -18.0 1009 overall baseline lesion counta: 513 -14.9 -16.7 887 moderate (iga=3) 435 -14.6 -26.0 122 severe (iga=4) 78 27.1 27.2 44.9 43.3 -15.1 p<0.001 p<0.001 p<0.001 % ig a tr ea tm en t s uc ce ss a t w ee k 12 b 0 20 40 10 30 60 50 50.6% 1009 overall 513 41.0% 52.5% 887 moderate (iga=3) 435 45.7% 36.8% 122 severe (iga=4) 78 14.9% p<0.001 p=0.01 p=0.003 n= n= fmx103 1.5% vehicle foam iga, investigator’s global assessment; integrated efficacy population (multiple imputation); abaseline lesion counts are based on observed cases. safety endpoints • overall summary of adverse events is shown in table 2 • all serious teaes were considered by the investigators as not related to study drug • 9 subjects reported 10 teaes resulting in study discontinuation – 7 subjects in the fmx103 1.5% group and 2 subjects in the vehicle group – one teae (moderate pruritis) leading to drug withdrawal was considered related to study drug. the subject was randomized to fmx103 1.5% treatment table 2. summary of teaes and aes in the integrated safety population fmx103 1.5% (n=1008) vehicle foam (n=513) overall (n=1521) subjects with any ae, n(%) 232 (23) 129 (25.1) 361 (23.7) number of aes 380 200 580 subjects with any teae, n(%) 219 (21.7) 122 (23.8) 341 (22.4) number of teaes 350 184 534 subjects with any serious teae, n(%) 3 (0.3) 5 (1.0) 8 (0.5) number of serious teaes 8a 9b 17 subjects with any treatment-related teae, n(%) 3 (0.3) 5 (1.0) 8 (0.5) number of treatment-related teaes 24c 17d 41 subjects with any teae leading to discontinuation, n(%) 7 (0.7) 2 (0.4) 9 (0.6) number of teaes leading to study discontinuation 8e 2f 10 anausea, chest discomfort, fatigue, seasonal allergy, dehydration, syncope, dyspnea, hypertension bgastrointestinal hemorrhage, chest pain, pyrexia, dyspnea, asthma, hypertension, myocardial infarction, tachycardia cpruritis, rash, dermatitis, dermatitis contact, hair color changes, nail discoloration, skin hyperpigmentation, application site pain, application site erythema, facial pain, nodule, migraine, dizziness, dysgeusia, aphthous ulcer, cheilitis, eye irritation, ophthalmic herpes simplex, sunburn dnail discoloration, rosacea, skin exfoliation, application site pain, facial pain, application site pruritis, headache, cellulitis, skin cancer, urine odor abnormal epruritis, dermal cyst, dermatitis, telangiectasia, influenza, urinary tract infection, bladder mass frash pustular, myocardial infarction • the incidence rate of the most frequently reported teaes (≥1% in any group) was similar between treatment groups (table 3) • overall, most subjects reported teaes that were not related to study drug (89.7%, 306/341) table 3. summary of non-cutaneous teaes in the integrated safety population by preferred term (≥1% in any group) teaes in ≥1% of subjects in either group, n (%) fmx103 1.5%(n=1008) vehicle foam (n=513) overall (n=1521) viral upper respiratory tract infection 24 (2.4) 12 (2.3) 36 (2.4) upper respiratory tract infection 19 (1.9) 13 (2.5) 32 (2.1) headache 14 (1.4) 10 (1.9)a 24 (1.6) sinusitis 11 (1.1) 2 (0.4) 13 (0.9) diarrhea 10 (1.0) 2 (0.4) 12 (0.8) a2 cases were considered to be treatment-related • the incidence rate of teaes by severity was similar between treatment groups (table 4) • overall, most subjects reported teaes that were mild (68.0%, 232/341) or moderate (29.9%, 102/341) in severity • 7 subjects (2.1%, 7/341) reported severe teaes • all severe teaes were considered not related to the study medication by the investigator table 4. summary of teaes by severity fmx103 1.5% (n=1008) vehicle foam (n=513) overall (n=1521) oa mild mod sevr oa mild mod sevr oa mild mod sevr subjects reporting any teae, n (%)a 219 (21.7) 145 (14.4) 71 (7.0) 3b (0.3) 122 (23.8) 87 (17.0) 31 (6.0) 4c (0.8) 341 (22.4) 232 (15.3) 102 (6.7) 7 (0.5) mod, moderate; oa, overall; sevr, severe. asubjects experiencing one or more adverse events are counted only once for each adverse event term and counted only by the maximum severity. if severity is missing, it is counted as severe. brosacea, post-traumatic headache, application site pain. cfall, dyspnea, asthma, pyrexia, myocardial infarction. • similar incidence rates of teaes were observed across both treatment groups for predefined subgroups (figure 6): – sex – race – age – baseline disease severity (iga) figure 6. summary of overall percentages of aes in all groups 0 15 45 50 a dv er se e ve nt s, % sex fmx103 1.5% vehicle foam 5 10 20 25 30 35 40 race age baseline iga severity female male white non-white 18-40 years 41-64 years ≥65 years iga 3 iga 4 22.9 25.7 18.7 19.5 21.5 23.4 27.8 31.8 18.5 26.3 22.3 22.2 25.2 26.2 23.0 21.821.6 24.1 • the majority of subjects in both treatment groups recorded local tolerability assessments as none or mild at both baseline and week 12 (figure 7) – similar rates of mild, moderate, and severe assessments were observed across both treatments and timepoints within each subgroup category – no notable differences were observed in facial tolerability assessments by subgroup – at week 12, all facial local tolerability assessments showed improvement compared to baseline – notable improvements in erythema were observed, with the percentage of patients with clear or almost clear signs of erythema increasing from 6.1% at baseline to 44.8% at week 12 figure 7. facial local tolerability assessments at baseline and week 12 in fmx103 1.5% treatment group bl wk 52 erythema bl wk 12 bl wk 12 bl wk 12 bl wk 12 bl wk 12 bl wk 12 bl wk 12 hyperpigmentation peeling/ desquamation itchingdryness/ xerosis flushing/ blushing burning/ stinging telangiectasia 10.55.1 34.3 28.9 36.2 63.8 18.3 0.7 clear severe moderate mild almost clear none mild moderate severe 1.3 1.0 12.5 20.2 52.3 83.9 17.1 50.5 37.4 72.0 44.2 76.7 57.2 81.9 64.9 74.754.8 61.0 27.6 13.3 38.7 39.0 36.8 23.9 35.0 20.0 31.5 16.1 28.3 22.532.6 18.8 19.8 2.8 40.3 9.6 25.2 4.0 20.1 3.3 11.0 1.9 6.8 2.8 0.1 0.0 0.3 0.0 4.0 0.9 0.6 0.1 0.6 0.0 0.2 0.1 0.0 0.0 0% 25% 50% 100% 75% s ub je ct s w ith lo ca l s ig ns o r sy m pt om s, % bl=baseline, n=1008; wk 12=week 12, n=897; all symptoms were evaluated on a 4-point scale consisting of 0=none, 1=mild, 2=moderate, and 3=severe, except for erythema, which was evaluated on a 5-point scale consisting of 0=clear, 1=almost clear, 2=mild, 3=moderate, and 4=severe. summary efficacy summary • fmx103 1.5% demonstrated efficacy over vehicle foam in treating papulopustular rosacea in a pooled population of ~1500 subjects, with effects being observed as early as 4 weeks into treatment • sub-analyses were performed on the integrated data set to characterize the efficacy of fmx103 1.5% in treating papulopustular rosacea in predefined subgroups of subjects – fmx103 1.5% demonstrated significant efficacy benefits in treating papulopustular rosacea in subgroups of subjects that had either moderate (iga=3) or severe (iga=4) disease severity at baseline, with a more pronounced effect in the severe subpopulation • findings from this integrated efficacy analysis are thus consistent with those from the individual phase 3 studies, both of which achieved statistically significant differences for all primary efficacy endpoints and further demonstrated significant differences as early as 4 weeks into treatment safety summary • fmx103 1.5% was generally safe and well tolerated • 341 (22.4%) subjects reported a teae during the 2 identical double-blind phase 3 studies – in general, no differences were observed between treatment groups in the incidence of teaes – the most frequently reported teaes for fmx103 1.5% vs vehicle, respectively, were viral upper respiratory tract infection (2.4% vs 2.3%), upper respiratory tract infection (1.9% vs 2.5%), and headache (1.4% vs 1.9%) – the majority of teaes reported were mild in severity (overall 68%) – 7 subjects reported severe teaes; all were considered to be unrelated to treatment, and were similar between treatment groups • teaes were similar across clinically relevant subgroups, including sex, race, age, and baseline iga score • at week 12, all facial tolerability assessments had higher percentages of “none” compared to baseline and trended towards improving scores in the fmx103 1.5% treatment group limitations • a limitation of these studies relates to the generalizability of the data to a more ethnically diverse population, or to patients not conforming to the inclusion criteria of the studies • an inclusionary criterion was to avoid common rosacea triggers, so efficacy would not be affected by such triggers conclusions • fmx103 1.5% demonstrated statistically significant differences compared with vehicle for both co-primary endpoints in a pooled population of two phase 3 studies, and numerical advantages across clinically relevant subpopulations • the results of the pooled safety analysis of 1,521 patients from two identical phase 3 studies demonstrated that fmx103 1.5% topical minocycline foam appeared to be safe and well tolerated with no serious treatmentrelated adverse events when administered daily for 12 weeks for the treatment of moderate-to-severe facial papulopustular rosacea disclosures/acknowledgment disclosures dr. del rosso is a consultant for aclaris, almirall, athenex, cutanea, dermira, ferndale, galderma, genentech, leo pharma, menlo, novan, ortho, pfizer, promius, sanofi/regeneron, skinfix, and sunpharma; he has received research support from aclaris, almirall, athenex, botanix, celgene, cutanea, dermira, galderma, genentech, leo pharma, menlo, novan, ortho, promius, regeneron, sunpharma, and thync; he receives honoraria from aclaris, celgene, galderma, genentech, leo pharma, novartis, ortho, pfizer, promius, sanofi/regeneron, and sunpharma; and he participates in speakers bureaus for honoraria from aclaris, celgene, galderma, genentech, leo pharma, novartis, ortho, pfizer, promius, sanofi/regeneron, and sunpharma. dr. stein gold is an advisor and investigator for foamix pharmaceuticals inc, galderma, leo pharma, novartis, and valeant and is an investigator for janssen, abbvie, and solgel. dr. kircik is an investigator and consultant for foamix pharmaceuticals. dr. bhatia is an investigator and consultant for foamix pharmaceuticals. dr. sadick is a consultant for almirall, galderma usa, venus concept, allergan, inc., auxilium pharmaceuticals, inc., btg plc, cynosure, inc., endo international plc, eternogen, ferndale loboratories, inc., gerson lehrman group, merz aesthetics, valeant pharmaceticals international; an advisor for slender medical ltd., galderma laboratories, l.p., merz aesthetics, suneva medical, inc., a stockholder in vascular insights, llc; a principal investigator for actavis, anacor pharmaceuticals, inc., bayer, biorasi, llc, cassiopea spa, celgene corporation, cynosure, inc., dusa pharmaceuticals, inc., eli lilly and company, endo international plc, galderma usa, hydropeptide, llc, neostrata, novartis, nutraceutical wellness, llc., palomar medical technologies, roche laboratories, samumed, llc, valeant pharmaceuticals international, vanda pharmaceuticals; a speaker for celgene corporation, cutera, inc., endymed medical inc. usa, solta medical, storz medical ag, and venus concept. dr. zirwas is a consultant for regeneron/sanofi, fit bit, l’oreal, menlo, leo, lilly, ortho derm, arcutis; an investigator for regeneron/sanofi, leo, janssen, incyte, foamix, ucb, pfizer, lilly, asana, avillion, abbvie, edessa biotech, galderma, dermavant, arcutis; a speaker for regeneron/sanofi, genench/novartis and part owner of asepticmd. dr. lain is an advisor, speaker, and investigator for foamix pharmaceuticals. dr. stuart is an employee and stockholder at vyne therapeutics inc. acknowledgment editorial support was provided by scient healthcare communications. funding this study is funded by foamix pharmaceuticals ltd, a wholly owned subsidiary of vyne therapeutics inc. references 1. li wq, cho e, khalili h, et al. rosacea, use of tetracycline, and risk of incident of inflammatory bowel disease in women. clin gastroenterol hepatol. 2016;14(2):220-225. 2. taieb a, gold ls, feldman sr, et al. cost-effectiveness of ivermectin 1% cream in adults with papulopustular rosacea in the united states. j manag care spec pharm. 2016;22(6):654-665. 3. rainer bm, kang s, chien al. rosacea: epidemiology, pathogenesis, and treatment. dermatoendocrinol. 2017;9(1):e1361574. 4. oge lk, muncie hl, phillips-savoy ar. rosacea: diagnosis and treatment. am acad fam physicians. 2015;92(3):187-196. 5. schaller m, schofer h, homey b, et al. rosacea management: update on general measures and topical treatment options. j dtsch dermatol ges. 2016;14(s6):17-27. 6. sapadin an , fleischmajer r. tetracyclines: nonantibiotic properties and their clinical implications. j am acad dermatol 2006;54:258-65. 7. mrowietz u, kedem th, keynan r, et al. a phase ii, randomized, double-blind clinical study evaluating the safety, tolerability, and efficacy of a topical minocycline foam, fmx103, for the treatment of facial papulopustular rosacea. am j clin dermatol. 2018;19(3)427-436. 8. stein gold l, del rosso jq, kircik l, et al. minocycline 1.5% foam for the topical treatment of moderateto-severe papulopustular rosacea: results of two phase 3, randomized, clinical trials. j am acad dermatol. 2020; doi: 10.1016/j.jaad.2020.01.043 skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 552 research letters high demand: identification of dermatology visit trends from 1991-2016 national ambulatory medical care surveys jade conway, ba1, bipasha roy, ba1, lauren barazani, ms1, albert g. wu, ms1, abigail cline, phd, md2, janet moy, md2 1new york medical college school of medicine, valhalla, ny 2department of dermatology, metropolitan hospital, new york, ny as demand for dermatology grows, physicians contend with more treatment options, electronic medical records, and billing systems. over a third of dermatologists report burnout, citing longer hours, excessive documentation, and lack of protected time.1 to maximize productivity and anticipate this field’s evolution, we should understand how dermatology has changed. utilizing the national summary tables from the national ambulatory medical care survey from 1991-2016, we analyzed office data and identified trends relating to dermatology visits over time. from 1991 to 2016, annual visit rates to dermatologists increased 68% (figure 1). visit length, defined as the time a patient spends with their dermatologist, increased 39%. in 1991, the average dermatology visit abstract background: the field of dermatology is constantly evolving and expanding to accommodate for increased demand. in order to maximize future productivity, it is important to recognize and understand how the desires of patients and the nature of physician visits have changed over time. objective: to evaluate and provide evidence-based reasoning for the changes occurring in the field of dermatology. methods: analysis of the 1991-2016 national summary tables from the national ambulatory medical care survey (namcs) was performed in order to identify several trends relating to dermatology visits. results: annual visit rates to dermatologists have increased by 68%, while visit length has increased by 39%. drug visits have increased by 86%, while drug mentions increased by 370.2%. limitations: limitations of this paper include a limited narrow timeline for data points. conclusion: as the field of dermatology will continue to expand in the future, dermatologists can expect to be busier than ever before. we expect that more patients will seek care, physician visits will be longer, and chief complaints and treatment options will continue to expand and vary. introduction results skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 553 figure 1: annual rate of dermatology visits. figure 2. annual rate of drug visits (visits at which one or more drugs were provided or prescribed) and drug mentions (documentation in a patient’s record of a drug provided, prescribed, or continued at a visit). skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 554 length was 14.9 minutes. in 2016, the average length was 20.7 minutes. the greatest change comes from the number of drug visits and mentions over time. a drug visit is an encounter where one or more drugs are prescribed or provided by the physician, while a drug mention is where a drug being prescribed, provided, or continued was documented in the patient’s record; drug mentions include all the drug visits.2 from 1991 to 2016, drug visits increased 86%, while drug mentions increased 370.2% (figure 2). the percent of visits with drug mentions increased by 21%, from 57.2% in 1991 to 69.1% in 2016. dermatologists now offer treatments including medical interventions to aesthetic procedures. this expansion may compel more patients to seek consultations, thereby increasing the numbers of annual visits. dermatologists spend more hours in the office each year, increasing availability for patients to secure appointments.1 the increased incidence of nonmelanoma and melanoma skin cancers may also account for the increased visits, as the average annual number of adults treated for skin cancer increased from 3.4 million in 20022006 to 4.9 million in 20072011.3 additionally, an increase in drug visits results in increased follow-up visits, as many dermatological conditions require lifelong management. social media may also play a role in the increase in patient visits. with readily available information on the internet, patients are more aware of their conditions and treatment options. another influence may be social media advertisements for cosmetic procedures, as well as posts of other patients’ procedural experiences. after viewing an online photograph highlighting a dissatisfying feature, over 80% of patients sought out aesthetic correction.4 explanations for longer dermatological visits include more patient concerns, discussion of treatment plan, and insurance requirements. the increase in dermatological procedures may be due to evolving beauty trends as well as greater physician interest in performing cosmetic procedures.5 surgical and cosmetic procedures can be time consuming, thus contributing to the increased visit length. steps taken in recent years to address these changes include increased utilization of support staff, physician extenders, and telemedicine.6 the percentage of dermatologists in solo practice dropped from 44% in 2005 to 35% in 2014. employment of physician assistants or nurse practitioners increased from 28% in 2005 to 46% in 2014.6 working in a group-based practice may allow physicians to spend less time performing administrative duties and more time seeing patients. teledermatology is another cost-effective strategy to decrease patient wait times while increasing satisfaction and access to healthcare. dermatology remains a growing field, pushed to evolve by advances in technology and healthcare demand. looking at the change in dermatology visits through the decades, we anticipate that visits will become longer, more patients will seek care, and dermatologists may be busier than ever before. further research is required to better understand the trajectory of the field, as the trends we identify are extrapolated from a narrow timeline of data points. discussion conclusion skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 555 conflict of interest disclosures: none funding: none corresponding author: jade conway, ba new york medical college school of medicine 40 sunshine cottage rd valhalla, ny 10595, united states email: jconway2@student.nymc.edu references: 1. colon a, gillihan r, motaparthi k. factors contributing to burnout in dermatologists. clin dermatol. 2020; 38(3): 321-327. doi:10.1016/j.clindermatol.2020.02.002 2. namcs/nhamcs ambulatory health care data homepage. centers for disease control and prevention. available from: https://www.cdc.gov/nchs/ahcd/. 3. guy gp jr, machlin sr, ekwueme du, yabroff kr. prevalence and costs of skin cancer treatment in the u.s., 2002-2006 and 2007-2011. am j prev med. 2015;48(2):183-187. doi:10.1016/j.amepre.2014.08.036 4. ross na, todd q, saedi n. patient seeking behaviors and online personas: social media's role in cosmetic dermatology. dermatol surg. 2015;41(2):269-276. doi:10.1097/dss.0000000000000267 5. neville ja, housman ts, letsinger ja, fleischer ab jr, feldman sr, williford pm. increase in procedures performed at dermatology office visits from 1995 to 2001. dermatol surg. 2005;31(2):160-162. doi:10.1111/j.15244725.2005.31037 6. ehrlich a, kostecki j, olkaba h. trends in dermatology practices and the implications for the workforce. j am acad dermatol. 2017;77(4):746-752. doi:10.1016/j.jaad.2017.06.030 rhbq primary wintercdc_poster_electronic_22dec2017_a4size_lah ! 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"! #! $! %! &!! ! " # $ % &! &" '()*+,-.#/! 012*3"4*+,-.5/! !"# " # # # # $ %& '( )& %* +, .%%/ ! "! #! $! %! &!! ! " # $ % &! &" '()*+,-$!.! /01*2"3*+,-$".! !"# $ # # # % &' () *' &+ ,. /&&0 ! "! #! $! %! &!! ! " # $ % &! &" '()*+,-#".! /01*2"3*+,-45.! !"# $% # 6 & ' () *+ ,) (./ 0 1((2 \rjfg,?>)+1-='.#)'-#' ;=#d%$& [-,#$+ 5+p%=)#(p ,>+ <-88+$,#-( -" ;+=?-(%8 .("-=3%,#-( \> +.'$$%$< &7%+ kt .,?#a >,1 '-# .,$+#$&%$< &, 7';# >,1dp '??-#++ '$?a %= >,1 .7,,+#a #/'%( '??-#++ &#/*,-'-%(> -#&'%$#? %$ ' +#.1-#? .,/*1&#+>+&#/ '$? 1+#? ,$(> =,.,1$&%$< *1-*,+#+a *#-=,-/%$< =%(# ?,6$(,'?a '$? +#$?%$< >,1 '$ #/'%(n p,1%$=,-/'&%,$ 6%(( $,& g# +7'-#? =,'$> ,&7#*1-*,+#a 1$(#++ -#81%-#? g> ('6n p,1 6%(( $,& -#.#%;# '$> =1&1-# .,//1$%.'&%,$+ =-,/ l(% c%((> '$? :,/*'$> g'+#? ,$ &7# +>+&#/h-#&'%$#? %$=,-/'&%,$n :,$&'.& %$=,-/'&%,$ '&w 7&&*wbb666n(%((>n.,/bp'<#+b.,$&'.&n'+*@ 5!*xja* w)('g%')/'c,-'a)('g%') /%$,-'a)'$?)*#-%$#1/ w)*#$%+a)+.-,&1/a)'$?) *#-%$#1/ *r-(?-=+)'4&'!8#'j#88&'%()'<-3r%(&'%()\-='-(+'-"'#,?'?24?#)#%=#+?'' therapeutic update gary goldenberg, md video length: 21:00 video description: in a cme podium lecture presented at the 2017 fall clinical dermatology conference® in las vegas, nevada, gary goldenberg, md, reviews late-breaking research covering the treatment of a broad selection of dermatologic disorders. background • acne vulgaris (av) is a chronic inflammatory disease that affects approximately 85% of adolescents and can also present in preand post-adolescents1 • oral antibiotics of the tetracycline class, including doxycycline and minocycline, are first-line therapies for moderate-to-severe acne; however, there are concerns with systemic side effects (eg, hyperpigmentation, phototoxicity, autoimmune disorders)2,3 • fmx101, minocycline foam 4%, is a novel, stable foam formulation of minocycline that has been previously demonstrated in a phase 2 study to be an effective and well-tolerated treatment for moderate-to-severe acne4 • two identical phase 3, randomized, double-blind studies were conducted to evaluate the efficacy and safety of the topical administration of fmx101 4% in the treatment of moderate-to-severe av – the 2 studies consisted of a 12-week double-blind phase followed by a 9-month open-label phase • this report presents data from the completed double-blind phase methods • two phase 3 (study 04 and study 05), randomized, double-blind, vehicle-controlled trials evaluated the safety and efficacy of fmx101 4% in the treatment of moderate-to-severe av (figure 1) – patients were randomized 2:1 to receive either fmx101 4% or a foam vehicle – foam was self-applied once daily for 12 weeks figure 1. study design methods • • • • • • • *subjects with ≥1-grade iga improvement. iga=investigator’s global assessment. results • 961 subjects (study 04: n=466; study 05: n=495) were enrolled in the studies • baseline demographics and disease characteristics are shown in table 1 table 1. baseline demographics and disease characteristics   study 04 study 05 fmx101 4% (n=307) vehicle (n=159) fmx101 4% (n=333) vehicle (n=162) demographics mean age (range), years 20.5 (11-52) 20.0 (10-57) 20.5 (10-55) 20.8 (11-54) male/female, % 45.3 / 54.7 38.4 / 61.6 40.8 / 59.2 42.6 / 57.4 ethnicity (white, black, other), % 62.5, 28.0, 9.5 62.9, 25.2, 11.9 73.0, 21.9, 5.1 76.5, 18.5, 5.0 inflammatory lesions, n mean (range) 32.2 (20-50) 31.6 (20-76) 31.6 (20-69) 32.3 (20-50) noninflammatory lesions, n  mean (range) 49.5 (25-100) 46.5 (25-98) 50.0 (25-100) 50.9 (26-104) iga score, n (%)  3 – moderate 255 (83.1) 137 (86.2) 296 (88.9) 148 (91.4) 4 – severe 52 (16.9) 22 (13.8) 37 (11.1) 14 (8.6) efficacy • after 12 weeks of treatment, subjects treated with fmx101 4% had a significantly greater reduction in inflammatory lesion count from baseline vs vehicle in both studies (figure 2a, b) • fmx101 4% was superior to vehicle for the first co-primary end point in the pooled analyses (all 961 subjects) (figure 2c) figure 2. co-primary end point – absolute change in inflammatory lesion count from baseline at week 12 results (cont.) • a greater proportion of subjects in both studies achieved iga treatment success with fmx101 4% vs vehicle at week 12 (figure 3a, b) – however, a statistically significant difference was achieved only in study 05; a numerical superiority was achieved in study 04 • in the pooled analysis of the 2 studies, fmx101 4% was significantly superior to vehicle for the second co-primary end point of iga treatment success (figure 3c) figure 3. co-primary end point – iga treatment success at week 12 results (cont.) • the percentage reduction in inflammatory lesions was significantly greater for fmx101 4% vs vehicle in both studies (figure 4) – a significantly greater reduction was observed as early as week 3 with fmx101 4% figure 4. percentage change from baseline to week 12 in inflammatory lesions by visit results (cont.) fmx101 (n=307) vehicle (n=159) fmx101 (n=333) vehicle (n=162) • subjects treated with fmx101 4% had a significantly greater reduction in noninflammatory lesion count from baseline at week 12 vs vehicle in both studies (figure 5a,b), as well as in the pooled analysis (figure 5c) figure 5. absolute change in noninflammatory lesion count from baseline at week 12 results (cont.) • there were high rates of subject satisfaction with using fmx101 4% (figure 6) – overall, 90% of subjects were satisfied with fmx101 4% – the majority of subjects were satisfied with fmx101 4% in comparison with previous acne products (ie, gels and creams), with its ease of use, and with the feel of the product on their skin figure 6. patient satisfaction questionnaire results (pooled analysis, n=534) results (cont.) safety • fmx101 4% was generally safe and well tolerated in both study 04 and study 05 • across the 2 studies, the percentage of subjects reporting treatment-emergent adverse events (teaes) ranged between 16.9% and 33% for fmx101 4%, vs 18.2% to 26.5% for vehicle (table 2) – 1 subject receiving fmx101 4% discontinued treatment in study 05 (ectopic pregnancy; not related to treatment), as compared with 4 subjects for vehicle across the 2 studies – 7 subjects reported 9 serious teaes across the 2 studies; all were considered not related to treatment – few treatment-related teaes were reported in both studies • the most common teaes in ≥2% of subjects were nasopharyngitis and headache (table 3) – dermal teaes were reported in <1% of all subjects in the fmx101 4% treatment groups; their severity was mostly mild • the majority (>95%)a of fmx101 4% subjects reported none or mild signs and symptoms for tolerability assessment parameters at week 12 (table 4) ªbased on observed cases. table 2. summary of treatment-emergent aes (teaes) study 04 study 05 fmx101 4% (n=307) vehicle (n=159) fmx101 4% (n=333) vehicle (n=162) subjects with any teae, n (%) number of teaes 52 (16.9) 78 29 (18.2) 35 110 (33.0) 169 43 (26.5) 80 subjects with any serious teae, n (%) number of serious teaes 1 (0.3) 1a 0 0 4 (1.2) 5b 2 (1.2) 3c subjects with any teae leading to study discontinuation, n (%) number of teaes leading to study discontinuation 0 0 3 (1.9) 4d 1 (0.3) 1e 1 (0.6) 1f subjects with any treatment-related teae, n (%) number of treatment-related teaes 6 (2.0) 7 4 (2.5) 6 9 (2.7) 10 3 (1.9) 4 asuicide attempt. bintestinal obstruction, intestinal perforation, facial bones fracture, ectopic pregnancy; asthma. cbiliary dyskinesia, cholecystitis, pneumonia. dapplication-site acne, application-site burn, application-site erythema, application-site pruritus. eectopic pregnancy. fhepatic enzyme increased. table 3. nondermal and dermal aes profile adverse event study 04 study 05 fmx101 4% (n=307) vehicle (n=159) fmx101 4% (n=333) vehicle (n=162) nondermal aes in ≥1% of subjects, % one or more 16.9 18.2 33.0 26.5 nasopharyngitis 2.0 3.8 7.2 3.7 headache 2.3 3.1 6.0 5.6 upper respiratory tract infection – – 1.8 1.2 ck increased 1.0 0.6 1.5 2.5 ligament sprain 0.3 1.3 1.8 0.6 nausea – – 1.2 0.6 vomiting – – 1.2 0.6 administration-site dermal aes, % acne worsening – 0.6 0.3 – burn – 1.3 – – dermatitis – – 0.3 – discolorationa 0.7 1.3 0.9 – discomfort 0.3 – – – erythema – 0.6 – – pruritus – 0.6 – – rash – – 0.3 0.6 aseveral terms were coded to “discoloration” including discoloration, yellow discoloration and, in 1 case, hyperpigmentation. ck=creatinine phosphokinase. table 4. tolerability assessment results at week 12 (based on observed cases) tolerability assessment, n (%) 0=none 1=mild 2=moderate 0=none 1=mild 2=moderate study 04 fmx 101 4% (n=267) vehicle (n=128) erythema 248 (92.9) 19 (7.1) – 124 (96.9) 4 (3.1) – dryness 250 (93.6) 17 (6.4) – 120 (93.8) 8 (6.3) – hyperpigmentationa 233 (87.3) 28 (10.5) 6 (2.2) 110 (85.9) 14 (10.9) 4 (3.1) skin peeling 259 (97.0) 8 (3.0) – 125 (97.7) 3 (2.3) – itching 254 (95.1) 12 (4.5) 1 (0.4) 124 (96.9) 3 (2.3) 1 (0.8) study 05 fmx101 4% (n=294) vehicle (n=136) erythema 238 (81.0) 49 (16.7) 7 (2.4) 102 (75.0) 29 (21.3) 5 (3.7) dryness 281 (95.6) 11 (3.7) 2 (0.7) 124 (91.2) 11 (8.1) 1 (0.7) hyperpigmentationa 237 (80.6) 44 (15.0) 13 (4.4) 118 (86.8) 15 (11.0) 3 (2.2) skin peeling 281 (95.6) 12 (4.1) 1 (0.3) 131 (96.3) 5 (3.7) – itchingb 274 (93.2) 18 (6.1) 2 (0.7) 123 (90.4) 12 (8.8) – ahyperpigmentation was most commonly used to describe localized post-inflammatory darkening of the affected skin. ba case of severe itching in the vehicle group. conclusions • the results of the 2 phase 3 studies showed that fmx101 4% was effective for the treatment of moderate-to-severe acne – there was significantly greater reduction of both inflammatory and noninflammatory lesions at week 12 from baseline with fmx101 4% vs vehicle in both study 04 and study 05, as well as in the pooled analysis (a co-primary end point) � a significant reduction in inflammatory lesions was observed as early as week 3 for fmx101 4% – the rate of iga treatment success was significantly greater for fmx101 4% vs vehicle in study 05, but not study 04 (a co-primary end point) � pooled analysis of iga treatment success was statistically significant for fmx101 4% • >95% of subjects had none or mild signs and symptoms at the week 12 assessment of dermal tolerability • fmx101 4% appeared to be safe and well tolerated, with dermal aes occurring in <1% of fmx101 4% subjects and no serious drug-related aes reported • there was high satisfaction with fmx101 4% • the fmx101 4% open-label phase is currently ongoing to determine long-term safety the efficacy and safety of fmx101, minocycline foam 4%, for the treatment of acne vulgaris: a pooled analysis of 2 phase 3 studies linda stein gold, md1; sunil dhawan, md2; jonathan weiss, md3; zoe diana draelos, md4; herman ellman, md5 1henry ford health system, detroit, michigan, usa; 2center for dermatology clinical research, inc., fremont, california, usa; 3gwinnett dermatology, braselton, georgia, usa; 4dermatology consulting services, high point, north carolina, usa; 5foamix pharmaceuticals, inc, bridgewater, new jersey, usa. references 1. picardo m, et al. dermatol ther (heidelb) 2017;7:43-52. 2. zaenglein al, et al. j am acad dermatol. 2016;74:945-973.e33. 3. smith k, leyden jj. clin ther 2005;27:1329-1342. 4. shemer a, et al. j am acad dermatol 2016;74:1251-1252. disclosures: this study was funded by foamix pharmaceuticals. dr. stein gold is speaker, consultant, or investigator for celgene, glaxosmithkline, janssen, kadmon, leo pharma, novartis, pfizer, regeneron pharmaceuticals, sun pharma, and valeant. dr. dhawan is an investigator or speaker for allergan, galderma, valeant, dr reddy’s, glenmark, abbvie, glaxosmithkline, foamix, dermira, aclaris, leo pharma, celgene, cutanea, regeneron, revance, amgen, ucb, novartis, pfizer, and merz. dr. weiss received grants for research from allergan, foamix, promius, galderma, and valeant, and he received honoraria for consulting from promius, galderma, valeant, and novan. dr. draelos received research grants from galderma, allergan, cutanea, valeant, and novan. dr. ellman is an employee of foamix pharmaceuticals. acknowledgment: editorial support was provided by princy john, pharmd, of p-value communications. poster presented at the winter clinical dermatology conference, january 12–17, 2018, lahaina, hi, usa introduction • the optima (efficacy of optimized retreatment and step-up therapy with omalizumab in patients with chronic idiopathic/spontaneous urticaria [ciu/csu]; nct02161562) study was designed to address some of the key gaps in the knowledge of optimal ciu/csu treatment with omalizumab1 • omalizumab is approved for the treatment of adults and adolescents (12 years and above) with ciu/csu who remain symptomatic despite h1-antihistamine treatment; in canada the approved dosage is omalizumab 150 mg or 300 mg every 4 weeks2 • the treatment algorithm proposed by international guidelines states that the disease should be treated to complete resolution of symptoms3 • to date, no data evaluating the efficacy of step-up therapy in patients inadequately controlled with omalizumab 150 mg are available omalizumab dose step-up and treatment response in patients with chronic idiopathic/spontaneous urticaria (ciu/csu): results from the optima study wayne gulliver,1 gordon sussman,2 jacques hébert,3 charles w. lynde,4 kim a. papp,5 william h. yang,6 olivier chambenoit,7 antonio vieira,8 frederica detakacsy,8 lenka rihakova8 1faculty of medicine, memorial university of newfoundland, st. john’s, nl, canada; 2department of medicine, university of toronto, toronto, on, canada; 3department of medicine, centre hospitalier de l’université laval, québec, qc, canada; 4lynde institute for dermatology, markham, on, canada; 5probity medical research inc., waterloo, on, canada; 6ottawa allergy research corporation, university of ottawa medical school, on, canada; 7novartis pharmaceuticals corporation, east hanover, nj, usa; 8novartis pharmaceuticals canada inc., dorval, qc, canada inclusion criteria • men or women at least 18 years of age • diagnosis of ciu/csu and the presence of symptoms for ≥6 months prior to the screening visit • patient must have been on an approved dose of nonsedating h1-antihistamine for ciu/csu, and no other concomitant ciu/csu treatment, for at least the 7 consecutive days immediately prior to the randomization visit and must have documented current use on the day of the randomization visit • uas7 score ≥16 (scale 0−42) and itch component of uas7 ≥8 (scale 0−21) during 7 days prior to randomization exclusion criteria • patients having a clearly defined underlying etiology for chronic urticaria other than ciu/csu • patients with urticarial vasculitis, urticaria pigmentosa, erythema multiforme, mastocytosis, hereditary or acquired angioedema, lymphoma or leukemia, active atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus or other skin disease associated with itch that could interfere with study outcomes • patients with a history of malignancy of any organ system • patients should stay on same approved dose of nonsedating h1-antihistamine during entire trial duration. no rescue medication was allowed methods study design • optima is a phase 3b, international, multicenter, randomized, open-label, noncomparator study • patients with ciu/csu who were symptomatic despite h1-antagonists at approved dose were randomized 4:3 to omalizumab 150 mg or 300 mg for 24 weeks (1st dosing period) • based on weekly urticaria activity score (uas7), patients entered one of the following phases: treatment withdrawal (if uas7 ≤6), step-up to 300 mg (if 150 mg initially and uas7 >6 at weeks ≥8 to 24), or continued treatment for 12 more weeks (if 300 mg initially and uas7 >6 at week 24) • patients who relapsed (uas7 ≥16) during the treatment withdrawal period were retreated with the same dose (omalizumab 150 mg or 300 mg every 4 weeks) during the 12-week second dosing period table 1. demographics and baseline characteristics characteristic omalizumab 150 mg (n=178) omalizumab 300 mg (n=136) overall (n=314) age, mean (range), years 46.7 (18–79) 45.8 (20–78) 46.3 (18–79) gender, % male female 27.0 73.0 27.2 72.8 27.1 72.9 race, % white asian black american indian/alaska native other 76.4 8.4 5.6 1.1 8.4 83.1 7.4 4.4 2.2 2.9 79.3 8.0 5.1 1.6 6.1 time to ciu/csu symptoms, n (%) ≤1 year >1–≤2 years >2–10 years >10 years 28 (15.7) 25 (14.0) 84 (47.2) 41 (23.0) 22 (16.2) 25 (18.4) 54 (39.7) 35 (25.7) 50 (15.9) 50 (15.9) 138 (43.9) 76 (24.2) baseline uas7, mean (range) 29.7 (16.0–42.0) 30.0 (16.0–42.0) 29.8 (16.0–42.0) # prior medications used for ciu/csu, mean (range) 1.8 (0.0–12.0) 2.1 (0.0–8.0) 1.9 (0.0–12.0) ciu/csu, chronic idiopathic/spontaneous urticaria; uas7, weekly urticaria activity score. • of those patients with ciu/csu treated with omalizumab 150 mg, 79.2% (141/178) had to be up-dosed to 300 mg • step-up treatment to omalizumab 300 mg led to a mean improvement of 9.7 points in uas7 when compared with the 150 mg dosing period • of those patients who had not been well controlled by omalizumab 150 mg, 45.4% were well controlled by omalizumab 300 mg during the step-up phase, and 25.4% of these were even symptom free results baseline characteristics scan this qr code visit the web at: http://novartis.medicalcongressposters.com/default.aspx?doc=f1660 mobile friendly e-prints 3 ways to instantly download an electronic copy of this poster to your mobile device or e-mail a copy to your computer or tablet text message (sms) text: qf1660 to: 8nova (86682) us only +18324604729 north, central and south americas; caribbean; china +447860024038 uk, europe & russia +46737494608 sweden, europe standard data or message rates may apply. • step-up treatment improved the disease severity scenario4 references 1. clinicaltrials.gov – nct02161562. 2. xolair [product monograph]. dorval, quebec: novartis pharmaceuticals canada inc.; april 2017. 3. zuberbier t, et al. allergy. 2014;69:868–87. 4. stull d, et al. eaaci 2014. funding this study was funded by novartis pharmaceuticals canada inc. disclosures authors declare the following, real or perceived conflicts of interest: wg, gs, jh, cwl, kap, and why received honoraria as investigators and consultants. oc, av, fdt, and lr are employees of novartis pharmaceuticals. acknowledgments the complete optima study team comprised: 35 active sites in the following countries: argentina, brazil, canada, chile, dominican republic, guatemala, mexico, and panama; syreon clinical research for project management and data management; sumeet sood, phd, novartis healthcare pvt ltd, hyderabad, india for medical writing and editorial support, which was funded by novartis pharma ag, switzerland in accordance with good publication practice (gpp3) guidelines; novartis pharmaceuticals canada and novartis in participating countries. all authors participated in the development of the poster and approved the final poster for presentation. editorial assistance in the development of this poster was provided by jessica donaldson-jones of fishawack communications, abingdon, uk. this poster was previously presented at the 26th european academy of dermatology and venereology congress, september 13–17, 2017, geneva, switzerland. contact information lenka rihakova – lenka.rihakova@novartis.com; antonio vieira – antonio.vieira@novartis.com; novartis pharmaceuticals canada: +1(514) 631 6775 314 randomized patients omalizumab 150 mg, 178 patients omalizumab 300 mg, 136 patients figure 2. patient randomization ratio screen & washout omalizumab 150 mg omalizumab 300 mg g ro u p a g ro u p b followup uas7 ≤6 uas7 <16 stop therapy omalizumab 300 mg omalizumab 150 mg r a n d o m iz a ti o n 4 :3 −5 to −1week 0 4 8 12 16 2420 0 4 8 12 0 4 uas7 ≤6 uas7 <16 stop therapy omalizumab 300 mg omalizumab 300 mg uas7 ≥16 uas7 ≥16 screen 1st dosing study treatment withdrawal 2nd dosing followup 0 4 8 uas7 >6 uas7 >6 uas7, weekly urticaria activity score. figure 1. optima study design. the study includes five phases: screening; initial dosing period; withdrawal; a second dosing period for retreatment, dose step-up, or dose extension based on uas7 response; and follow-up. well controlled 27 patients (15.2%) 314 randomized patients omalizumab 150 mg 178 patients discontinued 10 patients (5.6%) discontinued 5 patients (3.7%) omalizumab 300 mg 136 patients well controlled 88 patients (64.7%) extended treatment 43 patients (31.6%) step-up 141 patients (79.2%) figure 3. patient disposition after first dosing period week 24 n=141 week 20 n=141 week 16 n=141 week 12 n=141 81.6% 5.7% 6.4% 4.2% 2.1% 100 80 60 40 20 0 week 8 n=141 p ro p o rt io n o f p a ti e n ts s te p p in g u p ( % ) a) proportion of patients stepping up at scheduled visits c) mean uas7 during the second dosing period with omalizumab 300 mg baseline n=141 week 4 n=136 week 8 n=133 week 12b n=130 mean uas7 change from baseline 22.4 14.6 12.4 12.7 −7.8 −10.0 −9.7 −20 −10 0 10 20 30 40 m e a n (+ 9 5 % c i) u a s 7 m e a n c h a n g e fr o m b a s e li n e in u a s 7 m e a n (+ 9 5 % c i) u a s 7 m e a n c h a n g e (− 9 5 % c i) f ro m b a s e li n e in u a s 7 30.4 21.9 20.3 5.2 7.7 7.9 −8.5 −10.1 −22.3 −19.1 −16.8 −40 −30 −20 −10 0 10 20 30 40 baseline n=141 week 4 n=141 week 8a n=141 week 12 n=26 week 16 n=18 week 20 n=9 b) mean uas7 during the first dosing period with omalizumab 150 mg mean uas7 change from baseline figure 4. proportion of patients stepping up and patient response to omalizumab 150 mg (first dosing) and 300 mg (step-up) 100 80 60 40 20 0 well controlled (uas7 ≤6) (n=130) urticaria free (uas7 =0) (n=130) p ro p o rt io n o f p a ti e n ts ( % ) n=59 25.4% 45.4% n=33 uas7, weekly urticaria activity score. error bars represent 95% confidence level. figure 5. proportion of patients who were clinically well controlled (uas7 ≤6) or urticaria free (uas7 =0) at the end of step-up phase objectives • four objectives were to be answered in optima: − if a patient’s signs and symptoms of ciu/csu are well controlled with omalizumab and the treatment is stopped, will the patient relapse? how long will it take until relapse? − if omalizumab treatment is restarted, will the patient respond to retreatment? − if the patient does not sufficiently respond to omalizumab 150 mg, will step-up therapy to 300 mg improve the signs and symptoms of ciu/csu? − if the patient does not respond to 300 mg, will treatment extension improve the signs and symptoms of ciu/csu? • this poster will cover the third question baseline after step-up well controlled (uas7 ≤6) mild (>6 uas7 ≤16) moderate (>16 uas7 ≤28) severe (uas7 >28) p ro p o rt io n o f p a ti e n ts ( % ) 45.4% 23.8% 16.1% 14.6%uas7 =0 25.4% 0% 1.4% 40.4% 58.1% 100 80 60 40 20 0 figure 6. disease severity distribution at baseline and after step-up uas7, weekly urticaria activity score. a81.56% (n=15) patients were stepped up to omalizumab 300 mg by week 8. the data for weeks 12 to 20 are only for patients responding to omalizumab 150 mg. b11 patients out of 141 did not complete the step-up period or did not submit the participant diary as per protocol. ci, confidence interval; uas7, weekly urticaria activity score. conclusions • of the patients with ciu/csu treated with omalizumab 150 mg, 79.2% had to be up-dosed to 300 mg owing to insufficient symptom control • the mean uas7 improvement after the first dosing period and step-up therapy was 8.0 points and 9.7 points, respectively • from the step-up patient group, 45.4% of patients achieved symptom control during the 3-month treatment with omalizumab 300 mg • disease severity distribution was improved after dose step-up, with the majority of patients having well-controlled (45.4%) or mild (23.8%) disease powerpoint presentation vda-1102: a novel well-tolerated treatment for actinic keratosis chaim m. brickman, vered behar, galit zelinger, and oren m. becker vidac pharma, 10 hartom st, jerusalem, israel 9777510 in vivo efficacy non-clinical data conclusions composite local skin reaction score efficacy safety • vda-1102 is a selective hk2-modulator that triggers apoptosis in hk2expressing malignant cells such as ak and cscc, without effecting the surrounding normal tissue. • in a proof-of-concept phase 2a clinical trial, vda-1102 ointment (applied once-daily for 28 days) reduced the number of ak lesions on the face and scalp of adult subjects, while being very well-tolerated both locally (skin) and systemically. • a phase 2b dose-ranging trial with vda-1102 ointment (applied for 3 months) is currently ongoing. vda-1102: mechanism of action local skin reaction the means of the composite lsr scores from all 3 cohorts were indistinguishable (left panel) vda-1102 ingenol mebutate • actinic keratosis (ak) is a prevalent early-stage malignancy of the skin that can lead to cutaneous squamous cell carcinoma (cscc). • due to their mechanisms of action, current effective ak field treatments are irritating and painful, and cause unsightly skin eruptions. • these side effects result in hesitancy by both patients and physicians to initiate therapy, patient compliance issues, and/or unwillingness to re-treat lesions in the same treatment field. • furthermore, large populations susceptible to multiple aks (e.g. immunosuppressed, post-transplant, elderly patients) go untreated. • thus, an efficacious minimally-irritating topical treatment for ak is a pressing unmet medical need. actinic keratosis hexokinase (hk) is the first enzyme in the glycolysis pathway. the hk1 isoenzyme is ubiquitously expressed in normal cells while levels of the hk2 isoenzyme are often increased in cancer cells. in cancer cells, hk2 attaches to the outer mitochondrial membrane via interaction with the vdac1 channel. vdac1/hk2 association results in apoptosis prevention (i.e., cell longevity) and a high rate of glycolysis that addresses the transformed cells’ demand for energy and building blocks. hk2 in actinic keratosis & scc background clinical phase 2a data immunohistochemistry of skin biopsies from uvb damaged skh-1 hairless mice treated with placebo (for 2 days) or 5% vda-1102 (for 50 days). skh-1 hairless female mice were chronically exposed to uvb radiation for 16 weeks (by which time >60% of mice developed at least one lesion) followed by a 50-day treatment phase (n=12 mice/group). p values compare the 40% treatment group to the vehicle-control. *p≤0.05, **p≤0.01, ***p≤0.001, ****p≤0.0001. placebo 5% vda-1102 10% vda-1102 parent (vda-1102) blq blq blq major metabolite blq blq blq blq = below lowest level of quantitation: 1 ng/ml for vda-1102 and 20 ng/ml for major metabolite; n=4/group. pharmacokinetics facial ak lesions facial grade 2 ak lesions vda-1102 is a novel small-molecule hk2-modulator that triggers apoptosis and blocks glycolysis in hk2-expressing malignant cells. normal cells that do not express hk2 are unaffected by vda-1102. left panel: immunohistochemistry of sk208 and sk805 human tissue microarrays from us biomax; right panel: western blot; ht 297.t human ak cells; a431 human skin scc cells. high hk2 levels in human ak and scc cells high hk2 levels in skin scc vs. low hk2 levels in normal skin efficacy on uvb-damaged skin of hairless skh-1 mice day 50 hk1 & hk2 levels in ubv-damaged mouse skin 4-8 ak lesions (grades 1-2) in a 25cm2 area on face or scalp local skin reactions pharmacokinetic analysis for the parent compound (vda-1102) and for its major metabolite demonstrated no systemic exposure of either. reference: v. behar et al, “a hexokinase 2 modulator for field-directed treatment of experimental actinic keratoses”, journal of investigative dermatology (2018). skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 349 original research clinical efficacy & safety of oral polypodium leucotomos extract for photoprotection: a systematic review giselle prado md1, rebeca teplitz ba2, richard winkelmann do3, james del rosso do4, darrell rigel md, ms5 1national society for cutaneous medicine, new york, ny 2new york institute of technology college of osteopathic medicine, old westbury, ny 3department of dermatology, ohiohealth hospital 4jdr dermatology research, las vegas, nv 5department of dermatology, nyu school of medicine, new york, ny a complete sun protection package includes sun protective clothing, sunscreen, and avoidance of the midday sun. sun protection can also be affected by oral ingestion of certain compounds. psoralen is one such compound that leads to photosensitization. on the other hand, polypodium leucotomos extract (ple) has been shown to have photoprotective properties. polypodium leucotomos is a fern native to south america that is widely recommended by dermatologists for its antioxidant and photoprotective properties. ple does not act as a sunscreen, but has been shown to have background: polypodium leucotomos extract (ple) is a naturally derived compound from a fern native to south america. ple has been shown to have antioxidant and photoprotective properties. several different preparations of ple are commercially available. objective: to review the efficacy and safety of ple for photoprotection in humans. methods: a systematic review was conducted in 3 databases (medline, embase, and cochrane) for studies that reported on the clinical efficacy and safety of ple in humans. a data collection form was created for collecting study variables. results: eighteen studies with sample sizes ranging from n=5 to n-61 were included. the most common formulation of ple studied was fernblock® (heliocare, ferndale healthcare, ferndale, mi) in 18 studies. most studies reported beneficial photoprotective effects of ple as evidenced by increased med. no serious adverse effects were reported. conclusions: multiple studies have shown the beneficial photoprotective effects and safety of the fernblock® ple formulation, but there is minimal evidence to support the safety and efficacy of other formulations. given that the extraction methodology varies for herbal nutraceuticals and can affect its efficacy, these findings cannot be extrapolated to other formulations of ple. abstract introduction skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 350 some photoprotective efficacy. it works at both the molecular and cellular level to decrease uv-mediated cell apoptosis and necrosis. ple inhibits the generation of reactive oxygen species (ros) as well as uv-induced ap1 and nf-κb. it also prevents damage to dna and protects against endogenous antioxidant systems natural to the skin. 1 several different preparations of ple are commercially available. the most popular formulation of ple is heliocare (ferndale healthcare, ferndale, mi). however, the extraction methodology of an herbal supplement can affects its potency and effects in humans.2 without testing each specific formulation in humans, it can be difficult to compare different products that claim to have the same ingredients. this study reviews the efficacy and safety of ple for photoprotection in humans and determines the most studied formulations of ple. data sources: we searched three computerized bibliographical databases for articles published since inception to september 2018: pubmed, cochrane library central, and embase. search terms included: “polypodium leucotomos extract,” “oral sunprotection,” “heliocare,” and “fernblock.” the search was restricted to publications in english. this systematic review followed the preferred reporting items for systematic reviews and meta-analyses (prisma) guidelines (prospero registration no. crd42018106975). we reviewed trial registers (clinicaltrials.gov). reference lists of all included studies and of recent reviews were also assessed. electronic publications in advance of print were also included. inclusion criteria: we included any human studies that referenced polypodium leucotomos extract. exclusion criteria: case reports and studies done on animals or in-vitro were not included. outcome measures: outcomes related to change in sun protection efficacy included: minimal erythemal dose, minimal melanogenic dose, melanin index, melasma area and severity index (masi), melasma quality of life scale (melasqol), investigators global assessment of erythema, colorimetry, and erythema index. changes in skin quality were measured as transepidermal water loss, skin sebum content, wrinkle depth, and hydration. changes in histopathology were quantified by number of sunburn cells, cyclobutane pyrimidine dimers, proliferating cells, matrix metalloproteinase 1 levels, langerhans cells, and mast cells. data extraction and synthesis: one reviewer (g.p.) extracted data, another reviewer (r.t.) checked the extracted data for accuracy, and the reviewers met to discuss any disagreements. we created and piloted a data collection form for recording study design, sample sizes, primary outcomes, adverse events, and length of follow-up. disagreements were resolved by discussion. the search yielded 288 unique articles whose titles and abstracts were screened by 2 reviewers. full text papers were methods results skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 351 retrieved for 38 articles. eighteen studies were found to meet inclusion criteria (8 randomized controlled trials, 8 pre-post test studies, and 2 patient surveys). the studies tended to have relatively small sample sizes (n=5 to n=61). (table 1) the most common formulation of ple studied was fernblock® (ferndale healthcare, ferndale, mi) (17/18). most studies reported beneficial photoprotective effects of ple as evidenced by increased minimal erythemal dose (med). med was measured in 8 studies and results showed a uniform increase in med. 4,6,7,11,14,16,17,19 biopsies also showed the histologic effects of using ple. patients taking ple orally had lower numbers of sunburn cells, cyclobutane pyrimidine dimers, mast cells, and proliferating cells. 3,14,15 ple can also be used as an adjunctive treatment in polymorphous light eruption. three studies found a benefit to ple use in this population.16,20,21 although the level of evidence was lower for this indication (2 surveys and 1 pre-post exposure study), patients uniformly reported a decrease in symptoms. after irradiation, less patients developed polymorphous light eruption symptoms if they were taking ple. no serious adverse events were reported. the most common adverse event was mild gastrointestinal discomfort. skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 352 table 1: summary of studies investigating the photoprotective effects of ple. author & year study design comparators no. pts tx w/ oral ple no. pts comp arator tx. duration endpoints results gonzalez 19976 open label rct oral ple* 1080mg vs. topical ple 10% 12 9 1 day ipd, med, mmd, mpd ihc oral ple increased ipd, med (2.82x), mpd (2.75x) ihc: photoprotection of langherhans cells by oral and topical ple. vila 20107 single blind, rct oral ple* 240mg x 2 doses vs. no tx 5 5 1 day common deletion marker, med no difference in common deletion values. martin 20128 double blind, rct oral ple 240mg bid vs. placebo 21** 12 weeks melasqol, masi, physician and patient assessment ple improved masi and melasqol. physician and patient assessment showed more improvement with ple. ahmed 20139 double blind, rct oral ple* 240mg tid +sunscreen vs. placebo +sunscreen 16 17 12 weeks melanin index change, masi, melasqol melanin index improved 28.8% with ple and 13.8% with placebo group. masi improved in both groups. melasqol no change in either group. cestone 201410 single blind, rct oral ple* 240mg bid + sunscreen vs. placebo +sunscreen 20 10 12 weeks melanin index, tewl, wrinkle depth, skin moisturization , gloss value, elasticity, firmness decreased tewl, melanin index, and wrinkle depth with ple. increased skin moisture, gloss value, elasticity, and firmness with ple. no adverse events. nestor 201511 double blind, rct oral ple* 240mg bid vs. placebo 20 20 60 days med, uv induced erythema intensity response, sunburn, adverse events increased med and decreased uv induced erythema intensity with ple. less likely to have an episode of sunburn with ple. no adverse events. skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 353 emanuele 201712 rct oral ple* 480mg vs. ple/pomegr ante mix 480 mg 20 20 3 months sebum, hydration, tewl, melanin index, erythema index, elasticity improved hydration, elasticity, tewl, and erythema both groups. melanin index and skin sebum content reduced by only by mix. no adverse events goh 201813 double blind, rct oral ple* 240mg bid + hq & sunscreen vs placebo + hq & sunscreen 33 12 weeks mmasi, melanin index, erythema index, melasqol lower mmasi with ple. no difference in melanin, erythema index, or melasqol. no adverse events. middelkamp -hup 200314 open label, pre and post exposure oral ple* 7.5mg/kg vs. no tx not reported not reported erythema, edema, biopsies, med decreased erythema with ple. biopsy showed decreased sunburn cells, cpds, vasodilation, mass cell infiltration, and epidermal proliferation with ple. middelkamp -hup 20043 open label, pre and post exposure oral ple* 7.5mg/kg x 2 doses 9 n/a 72 hours erythema, biopsies decreased erythema with ple. biopsy showed decreased sunburn cells, cpds, proliferating cells, and mast cells with pl. middelkamp -hup 200415 open label, pre and post exposure oral ple* 7.5mg/kg x 2 doses 10 n/a 1 day mpd, erythema and edema intensity, biopsies decreased erythema and edema intensity with ple after 48-72 hours biopsy showed decreased . sunburn cells, mast cells, amd vasodilation. no differences in proliferating cells. skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 354 tanew 201216 open label, pre and post exposure oral ple* 720mg to 1200mg daily in patients with polymorphou s light eruption 30 n/a 1 month med, no. of exposures to induce symptoms, no. of patients with induced symptoms 30% reduction in number of patients with induced symptoms after uva. 28% reduction in number of patients with induced symptoms after uvb. mean number of uva or uvb exposures to elicit symptoms increased with ple. increased med with ple. no adverse events reported aguilera 20124 open label, pre and post exposure oral ple* 1080mg 61 n/a 1 day med, melanoma gene mutation testing increased med with ple in 65% of patients. no difference in med between patients with melanoma gene variants. calzavarapinton 201517 pre and post exposure testing oral ple* 240mg bid 10 n/a 2 weeks med, mmd increased med with ple. no change in mmd. truchuelo 201618 pre and post exposure testing oral ple* 960mg daily 7 n/a 3 weeks biopsy, mmp1 levels without ple, mmp1 levels increased in 71% of patients. with ple, mmp1 levels increased in 14% of patients. structure of epidermis unchanged by irradiation. kohli 201719 open label, pre and post exposure oral ple* 240mg x 2 doses 22 n/a 1 day erythema, med, colorimetry, biopsies decrease in uvb -induced changes with ple detected by clinical assessments, colorimetry. increased med in 32% of patients with ple. colorimetry showed decrease in uvb -induced changes in 77% of patients. skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 355 decreased effect of uv on h&e biomarkers. caccialanza 200720 open label, post exposure survey oral ple* 240mg bid in patients with solar urticaria or polymorphou s light eruption 25 n/a 15 days frequency and severity of skin manifestation s 80% of patients had an improvement in symptoms. 28% had normalization of symptoms. not effective in solar urticaria. caccialanza 201121 open label, post exposure survey oral ple* 240mg bid in patients with solar urticaria or polymorphou s light eruption 57 n/a not reported frequency and severity of skin manifestation s 74% of patients had an improvement in symptoms. no adverse events. *fernblock formulation. **distribution not reported. bid: twice daily. cpd: cyclobutane pyrimidine dimer. ihc: immunohistochemistry. ipd: immediate pigment darkening. hq: hydroquinone. masi: melasma area and severity index. mmasi: modified melasma area and severity index. med: minimal erythemal dose. melasqol: melasma quality of life scale. mmd: minimal melanogenic dose. mpd: minimal pigment dose. n/a: not applicable. no.: number. tewl: transepidermal water loss. tid: three times daily. tx: treatment. vs: versus skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 356 uv light can have harmful effects on the skin, including sunburn, immunosuppression, pigment changes, photoaging, and skin cancer.3 currently, the most widely used method for protection against uv damage is the use of topical sunscreens, which act as either a chemical or physical barrier against these harmful rays.4 these topical sunscreens often fail to provide a uniform and prolonged total body surface protection. as a result of the rise of spray sunscreen use and the lack of proper application guidelines, there is a need for a systemic photoprotective agent.5 this systematic review demonstrates the photoprotective effects of ple. however, it is important to note that while ple decreases photosensitization, it serves as an additional component to other sun protection measures. our systematic review was extensive with a precisely executed search strategy and selection process. it serves as an up to date resource for the efficacy and safety effects of ple. multiple studies have shown the beneficial photoprotective effects and safety of the fernblock® ple formulation, but there is minimal evidence to support the safety and efficacy of other formulations. given that the extraction methodology varies for herbal nutraceuticals and can affect its efficacy, these findings cannot be extrapolated to other formulations of ple. conflict of interest disclosures: dr. prado is a fellow of the national society for cutaneous medicine. funding: this study was supported in part through an unrestricted grant to the national society for cutaneous medicine from ferndale healthcare. corresponding author: giselle prado, md national society for cutaneous medicine, new york, ny email: drgiselleprado@gmail.com references: 1. gonzález s, gilaberte y, philips n, juarranz á. fernblock, a nutriceutical with photoprotective properties and potential preventive agent for skin photoaging and photoinduced skin cancers. int j mol sci. 2011;12(12):8466–8475. 2. ong es. extraction methods and chemical standardization of botanicals and herbal preparations. j chromatogr b analyt technol biomed life sci. 2004;812(1-2):23-33. 3. middelkamp-hup ma, pathak ma, parrado c, et al. oral polypodium leucotomos extract decreases ultraviolet-induced damage of human skin. j am acad dermatol. 2004;51(6):910-8. 4. aguilera p, carrera c, puig-butille ja, et al. benefits of oral polypodium leucotomos extract in mm high-risk patients. j eur acad dermatol venereol. 2013;27(9):1095-100. 5. teplitz, r. w., glazer, a. m., svoboda, r. m., rigel, d. s. (2018). trends in us sunscreen formulations: impact of increasing spray usage. j am acad dermatol. 78 (1): 187-189. 6. gonzalez s, pathak ma, cuevas j, et al. topical or oral administration with an discussion conclusion skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 357 extract of polypodium leucotornos prevents acute sunburn and moraleninduced phototoxic reactions as gel1 as depletion of langerhans cells in human skin. photodermatol photoimmunol photomed 1997;13:50-40 7. villa a, viera mh, amini s, et al. decrease of ultraviolet a light-induced "common deletion" in healthy volunteers after oral polypodium leucotomos extract supplement in a randomized clinical trial. j am acad dermatol. 2010;62(3):511-3. 8. martin lk, caperton c, woolery-lloyd h, et al. a randomized double blind placebo controlled study evaluating the effectiveness and tolerability of oral polypodium leucotomos in patients with melasma. american acad of dermatol annual meeting. 2012; poster# 4630. 9. ahmed am, lopez i, perese f, et al. a randomized, double-blinded, placebocontrolled trial of oral polypodium leucotomos extract as an adjunct to sunscreen in the treatment of melasma. jama dermatol. 2013;149(8):981-3. 10. cestone e, marzatico f, nobile v, et al. placebo-controlled study of the efficacy of a dietary supplement to reduce skin dark spots and to create more even complexion in asian women. pigment cell melanoma res. 2014;27(5):995. 11. nestor ms, berman b, swenson n. safety and efficacy of oral polypodium leucotomos extract in healthy adult subjects. j clin aesthet dermatol. 2015;8(2):19-23. 12. emanuele e, bertona m, biagi m. comparative effects of a fixed polypodium leucotomos/pomegranate combination versus polypodium leucotomos alone on skin biophysical parameters. neuro endocrinol lett. 2017;38(1):38-42. 13. goh cl, chuah sy, tien s, thng g, vitale ma, delgado-rubin a. double-blind, placebo-controlled trial to evaluate the effectiveness of extract in the treatment of melasma in asian skin: a pilot study. j clin aesthet dermatol. 2018;11(3):14-19. 14. middelkamp-hup ma, pathak ma, parrado c, et al. oral polypodium leucotomos extract protects human skin against the damaging effects of ultraviolet radiation and puva exposure. j eur acad dermatol venereol. 2003;17:160. 15. middelkamp-hup ma, pathak ma, parrado c, et al. orally administered polypodium leucotomos extract decreases psoralen-uva-induced phototoxicity, pigmentation, and damage of human skin. j am acad dermatol. 2004;50(1):41-9. 16. tanew a, radakovic s, gonzalez s, venturini m, calzavara-pinton p. oral administration of a hydrophilic extract of polypodium leucotomos for the prevention of polymorphic light eruption. j am acad dermatol. 2012;66(1):58-62. 17. calzavara-pinton pg, rossi mt, zanca a, et al. oral polypodium leucomotos increases the anti-inflammatory and melanogenic responses of the skin to different modalities of sun exposures: a pilot study. photodermatol photoimmunol photomed. 2016;32:2227. skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 358 18. truchuelo m, jiménez n, mascaraque m, et al. pilot study to assess the effects of a new oral photoprotector against infrared-visible radiations. j invest dermatol. 2016;136(5):s106. 19. kohli i, shafi r, isedeh p, et al. the impact of oral polypodium leucotomos extract on ultraviolet b response: a human clinical study. j am acad dermatol. 2017;77(1):33-41.e1. 20. caccialanza m, percivalle s, piccinno r, brambilla r. photoprotective activity of oral polypodium leucotomos extract in 25 patients with idiopathic photodermatoses. photodermatol photoimmunol photomed. 2007;23(1):46-7. 21. caccialanza m, recalcati s, piccinno r. oral polypodium leucotomos extract photoprotective activity in 57 patients with idiopathic photodermatoses. g ital dermatol venereol. 2011;146(2):85-7. skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 94 original research adaptations of dermatology residency programs to changes in medical education amid the covid-19 pandemic: virtual opportunities and social media reagan h. hattaway, bs1, nikhi p. singh, bs1, soroush rais-bahrami, md2, lauren c.s. kole, md3 1school of medicine, university of alabama at birmingham, birmingham al 2department of urology, university of alabama at birmingham, birmingham al 3department of dermatology, university of alabama at birmingham, birmingham al the covid-19 pandemic has caused a drastic change in the 2020-2021 residency application process.1 the consensus statements released by dermatology residency program directors and the association of american medical colleges (aamc) recommend limitation of visiting medical student sub-internships (visiting rotations) and in-person interviews.2,3 traditionally, visiting rotations for students interested in dermatology were critical for abstract background: the covid-19 pandemic has caused a drastic change in the 2020-2021 residency application cycle, limiting how programs interact with applicants. objective: to describe how dermatology residency programs have adapted by developing social media platforms and virtual opportunities. methods: a list of participating programs was obtained from the electronic residency application service. twitter, instagram, facebook, and websites were reviewed for virtual opportunities. the visiting student application service (vsas) and the dermatology interest group association (diga) website were reviewed for virtual opportunities. results: of the 133 programs, 74 social media accounts were created. twenty-two programs have twitter, 27 have instagram, and 25 have facebook accounts. virtual open houses were advertised on 27 program webpages. eight virtual sub-internships were on vsas. eighty virtual meet and greets and 27 virtual electives were advertised on the diga website. limitations: considering the ongoing application cycle and the growth of social media usage, the numbers presented may not represent the numbers on the date of publication. conclusion: dermatology residency programs have adapted to the covid-19 pandemic by developing social media platforms and virtual opportunities. there is an underutilization of social media by programs. programs are working with the diga to distribute information about virtual opportunities. introduction skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 95 obtaining letters of recommendation and showing interest in specific programs. a study conducted in 2016 found that, for applicants applying to competitive specialties, greater than 50% matched at an institution where they rotated and 53% were compelled to rank programs lower based on their visiting rotation experience.4 many medical students interested in dermatology have limited exposure during their preclinical training and are not able to complete sub-internships until shortly before application deadlines.5 loss of in-person electives and interviews may decrease the exposure an applicant has to the field and may also impact applicants’ impressions of various training programs. the american academy of dermatology (aad) has encouraged programs to adapt to this changing dynamic and recommended the use of virtual didactics to engage students during this time.6 a study in 2019 described the underutilization of social media by dermatology residencies.7 herein, we describe how dermatology programs have adapted for the 2020-2021 application cycle by developing social medial platforms and implementation of virtual sub-internships, virtual open houses, and other virtual opportunities. an official list of accredited dermatology residency programs participating in the 2020-2021 application cycle was obtained from the electronic residency application service (eras), identifying 133 total programs. all programs were included and reviewed for the presence of departmental and/or residency program twitter, instagram, and facebook accounts. this review was done using google search engine to account for the use of acronyms in social media usernames. social medial platforms were reviewed for posts regarding open house/meet and greet opportunities, virtual sub-internships, virtual grand rounds, and other virtual didactics. the posts analyzed were current in 2020. both past and future virtual opportunities were included. the date of twitter account development was available on the account page. the date of instagram and facebook account development was recorded as the first post on the respective pages. the visiting student application service (vsas) was reviewed for all dermatology virtual subinternship opportunities. virtual research electives were not included. residency program websites were reviewed for virtual sub-internship and open house opportunities. this data was collected and deemed current on september 8th-11th, 2020. the dermatology interest group association (diga) website was reviewed for virtual meet and greets/open houses and virtual electives. this data was collected and deemed current on september 23rd, 2020. of the 133 programs, 74 social media accounts were created for dermatology departments and residency programs. social media use of the 133 programs are profiled in table 1. twenty-two (16.5%) departments and/or residency programs have twitter accounts, 27 (20.3%) have instagram accounts, and 25 (18.8%) have facebook accounts. all twitter accounts were developed between 2014-2020. three (13.6%) of the accounts were developed in 2020. all instagram accounts were developed between 2015-2020. fourteen (51.9%) of the instagram accounts were developed in 2020. all facebook accounts were developed between 2008-2020. four (16%) facebook accounts were developed methods results skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 96 table 1. virtual characteristics of dermatology departments and residency programs. number and percentage of twitter, instagram, and facebook accounts for dermatology departments and/or residency programs. number of accounts created by dermatology departments and/or residency programs before and after 2020. number of open houses, virtual grand rounds, virtual sub-i, and virtual electives/didactics opportunities on twitter, instagram, and facebook. social media platform total dermatology programs (133) twitter number of accounts (%) programs with departmental twitter 19 (14.3) established before 2020 17 (89.4) established after 2020 2 (10.5) residency program twitter 3 (2.3) established before 2020 2 (66.7) established after 2020 1 (33.3) programs with both departmental and residency twitter 1 (0.8) programs with open house opportunities advertised on twitter 10 (7.5) programs with virtual grand rounds advertised on twitter 0 (0) programs with virtual sub-is advertised on twitter 0 (0) programs with virtual electives/didactics advertised on twitter 2 (1.5) instagram departmental instagram 16 (12.0) established before 2020 9 (56.3) established after 2020 7 (43.8) residency program instagram 11 (8.3) established before 2020 1 (9.1) established after 2020 10 (90.9) both departmental and residency instagram 2 (1.5) programs with open house opportunities advertised on instagram 9 (6.8) programs with virtual grand rounds advertised on instagram 2 (1.5) programs with virtual sub-is advertised on instagram 0 (0) programs with virtual electives/didactics advertised on instagram 1 (0.75) facebook departmental facebook 21 (15.8) established before 2020 20 (95.2) established after 2020 1 (4.8) residency facebook 4 (3.0) established before 2020 1 (25) established after 2020 3 (75) both departmental and residency facebook 0 (0.0) programs with open house opportunities advertised on facebook 7 (5.3) programs with virtual grand rounds advertised on facebook 1 (0.75) programs with virtual sub-is advertised on facebook 0 (0) programs with virtual electives/didactics advertised on facebook 2 (1.5) in 2020. the dates of development of social medial accounts are illustrated in figure 1. virtual open houses were advertised on 27 (20.3%) residency program webpages. of those 27 programs, 10 programs also advertised virtual open house opportunities on social media. only 1 program offered virtual opportunities on all 3 social media platforms. seven programs offered a total of 8 virtual sub-internship opportunities on vsas. these opportunities ranged from 2-4 weeks, with the mean (sd) length per program being 3.125 (±0.99) weeks. the number of virtual sub-internship periods listed per program ranged from 1 to 2. the mean number of virtual sub-internship skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 97 figure 1. dermatology program twitter, instagram, and facebook accounts added each year 2008-2009. table 2. diga virtual opportunities: details and characteristics. diga virtual opportunities and characteristics number of virtual meet and greets on diga, n 80 mean number of virtual meet and greets per program, mean ± sd 2.1±1.16 number of virtual electives on diga, n (%) 27 (20%) mean length of virtual elective, mean ± sd 2.7±1.64 weeks number of virtual electives with course credit, n (%) 11 (40%) number of virtual electives that guarantee and interview, n (%) 2 (7%) opportunity to meet with program leadership through virtual elective, n (%) 21 (78%) opportunity to meet with faculty through virtual elective, n (%) 17 (63%) opportunity to meet with residents through virtual elective, n (%) 20 (74%) opportunities on vsas was 1.12±0.35 per program. there were 80 virtual meet and greets advertised on the diga website. of the 38 programs offering virtual meet and greets, the number offered per program ranged from 0 to 5. eighty-four institutions are members of diga. fifty-six (42%) of the 133 participating programs have dermatology interest group chapters at their institutions. twenty-seven programs advertised virtual electives on diga. contact information and application deadlines for the programs were included. two programs had rolling deadlines, while 18 programs had no deadline for application. one program had a deadline in july. three programs had application deadlines in august. three programs had deadlines in september, and one program had a deadline in october. students can also find skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 98 information about telemedicine and educational opportunities during the virtual electives offered. some virtual electives count as course credit, include an interview, and provide an opportunity to meet residency leadership, faculty, and residents (table 2). the development of social media accounts by dermatology programs has been trending upward since 2008, with the earliest accounts created on facebook. before 2019, more programs appeared to have developed facebook and twitter accounts rather than instagram accounts. the increase in creation of instagram accounts by dermatology departments and residency programs reflects the overall rise in popularity of instagram in recent years.8 a 2019 study analyzing 126 dermatology residency programs identified 29 (23%) active on facebook, 14 (11%) on twitter, and 9 (7%) on instagram.7 this supports the notion that the covid-19 pandemic has stimulated social media development in 2020. despite the popularity of social media, only 74 social media accounts have been created by dermatology departments and residency programs, and fewer than 10% of those programs advertised virtual open houses, virtual sub-internships, virtual electives/didactics, or virtual grand rounds (table 2). specialties such as urology and emergency medicine have demonstrated a benefit in learning, feedback, and collaboration from increased engagement over twitter.9,10 this suggests that dermatology may be underutilizing this resource, and that residency training programs continue to have large potentials for growth. due to the visual nature of dermatology, social media may provide an even greater learning opportunity for those interested in the field. eight virtual sub-internships were available on vsas and 27 virtual electives were advertised on webpages and the diga website. this can be compared to the 80 virtual meet and greets that were included on the diga website. this suggests that programs are more likely to use virtual open houses and meet and greets to reach applicants rather than develop a virtual internship experience. this method of outreach has both benefits and drawbacks. though the aad developed a standardized online curriculum, open houses and informal didactics may be easier to convert to a virtual format and may be an easier way to reach a larger number of applicants.11 residency programs may face extra restrictions when developing virtual subinternships that they would not face when offering virtual didactics and electives that are not for course credit. despite this, 40% of the virtual electives offered on diga will count as course credit. traditionally, many students who did away rotations were granted interviews at those institutions. only 2 of the virtual electives on diga included an interview even though over 60% of these electives provide an opportunity for students to interact with program leadership, faculty, and residents (table 2). this greatly increases networking opportunities for students but may not be enough interaction to gain an interview. the quality of virtual interactions may be lesser than that of inperson interactions due to difficulty assessing body language, subtle expressions, and changes in tone of voice via video. virtual open houses may not allow for efficient networking compared to inperson interactions, but virtual interviews or “breakout rooms” on virtual platforms do allow for personal connections to be made amongst a smaller number of people. virtual discussion skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 99 grand rounds are also being offered by various programs as a way for students to interact with faculty and learn more about dermatology. all of these virtual opportunities may provide applicants an opportunity to become familiar with programs that they would not have considered during a typical application cycle due to limited visiting rotations and interview spots. although students may be familiar with a wider variety of programs through virtual interviews, they are not able to assess the hospital environment, surrounding city, or see interactions among faculty members and residents. the current predicament for students is double edged. in this case, quantity may not equal quality. dermatology residency programs are using methods other than social media to communicate with applicants. the information on the diga website was supplied by dermatology residency programs and sent to applicants via email. eighty-four us medical schools are members of the diga and 16 dermatology faculty from various institutions sit on the faculty advisory panel. this information is easily accessed on the diga website and is included on a calendar for easy use by applicants. the diga also has twitter, instagram, and facebook accounts. information about these virtual opportunities can be found there as well. when looking at only social media and websites, it would seem as if dermatology residencies were not reaching out to students. for this reason, it is important for applicants to be involved with the diga and the dermatology interest group at their home institution. students should also become more involved at their home institutions, as letters of recommendation and program director communication may become more important. students without access to a clinical experience in dermatology at their home institution may participate in rotations at other institutions during this time. often, larger institutions within the same state or geographic area are allowing these students to continue to participate in visiting rotations. 12,13,14 considering the ongoing application cycle and the increasing growth of social media platforms by dermatology residency programs, the numbers presented in this study will most likely not represents the actual numbers on the date of publication. it is possible that not all programs with social media accounts were found due to the use of acronyms in usernames and browsing limitations on the internet. google searches may not display social media platforms with less activity. also, video tours and introductions were not included in this study. virtual grand rounds and didactic videos present on websites were not included in this study. dermatology residency programs have adapted to the covid-19 pandemic through the development of social media platforms, virtual sub-internships, and virtual open houses for applicants. instagram was the most popular platform among residency programs, and facebook was the most popular platform among dermatology departments. overall, there has been an underutilization of these resources by academic dermatology programs. dermatology residency programs are working together through the diga to distribute information about virtual meet and greets and virtual electives to applicants. each medical specialty may have different avenues of communication with applicants, limitations conclusion skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 100 all of which must be assessed for a comprehensive analysis of the 2020-2012 application cycle. this data is subject to evolve as the application cycle progresses. conflict of interest disclosures: none funding: none corresponding author: lauren c.s. kole, md 510 20th street s. fot suite 858 birmingham, al 35233 phone: 205-934-5188 fax: 205-934-5766 email: laurenkole@uabmc.edu references: 1. hammoud mm, standiford t, carmody jb. potential implications of covid-19 for the 20202021 residency application cycle. jama j am med assoc. published online 2020. doi:10.1001/jama.2020.8911 2. dermatology residency program director consensus statement on 2020-21 application cycle. https://aamcorange.global.ssl.fastly.net/production/media/filer _public/0f/7b/0f7b547e-65b5-4d93-8247951206e7f726/updated_dermatology_program_d irector_statement_on_2020-21_application_cycle 3. association of american medical colleges. specialty response to covid-19. assoc am med coll . https://studentsresidents.aamc.org/applyingresidency/article/specialty-response-covid-19/ 4. higgins e, newman l, halligan k, miller m, schwab s, kosowicz l. do audition electives impact match success? med educ online. 2016;21:31325. doi:10.3402/meo.v21.31325 5. mccleskey pe, gilson rt, devillez rl. medical student core curriculum in dermatology survey. j am acad dermatol. published online 2009. doi:10.1016/j.jaad.2008.10.066 6. stewart cr, chernoff ka, wildman hf, lipner sr. recommendations for medical student preparedness and equity for dermatology residency applications during the covid-19 pandemic. j am acad dermatol. 2020;83(3):e225-e226. doi:10.1016/j.jaad.2020.05.093 7. st claire km, rietcheck hr, patel rr, dellavalle rp. an assessment of social media usage by dermatology residency programs. dermatol online j. published online 2019. 8. michael d. demographics of social media users and adoption in the united states | pew research center. soc media fact sheet. published online 2018. https://www.pewresearch.org/internet/factsheet/socialmedia/%0ahttps://www.pewresearch.org/internet/ fact-sheet/socialmedia/%0ahttps://www.pewresearch.org/ 9. diller d, yarris lm. a descriptive analysis of the use of twitter by emergency medicine residency programs. j grad med educ. 2018;10(1):51-55. doi:10.4300/jgme-d-1600716.1 10. chandrasekar t, goldberg h, klaassen z, et al. twitter and academic urology in the united states and canada: a comprehensive assessment of the twitterverse in 2019. bju int. published online 2020. doi:10.1111/bju.14920 11. cipriano sd, dybbro e, boscardin ck, shinkai k, berger tg. online learning in a dermatology clerkship: piloting the new american academy of dermatology medical student core curriculum. j am acad dermatol. 2013;69(2):267-272. doi:10.1016/j.jaad.2013.04.025 12. final report and recommendations submitted by the coalition for physician accountability's work group on learner transitions from medical schools to residency programs in 2020. published 2020. accessed february 3, 2021. 13. tsda recommendations on visiting external medical student rotations during the covid-19 pandemic. accessed february 3, 2021. https://aamcorange.global.ssl.fastly.net/production/media/filer _public/7d/38/7d3855d8-d317-4909-a50216f6db60d2cd/final-tsda-recommendations-5-272020_visting_external_med_student_rotations.pd 14. faqs on sns external medical student rotation policy during the covid-19 pandemic. accessed february 3, 2021. https://societyns.org/medicalstudents/external-medical-student-rotations mailto:laurenkole@uabmc.edu skin may 2019 volume 3 issue 3 copyright 2018 the national society for cutaneous medicine 219 brief articles unusual presentation and successful treatment of necrobiosis lipoidica in a 15-year-old girl allison l limmer, bs, ba1, levi c holland, bs1, annabelle l garcia, md2 1mcgovern medical school at uthealth, houston, tx 2independent researcher, san antonio, tx necrobiosis lipoidica (nl) is a rare, disfiguring, granulomatous skin condition commonly affecting the pretibial region. classically, histopathologic analysis reveals granulomatous inflammation, sclerosis, and altered connective tissue spanning the dermis with or without palisading histiocytes and giant cells. in fact, the term “necrobiosis” refers to the connective tissue changes, as it appears more pale, gray, compact, and disorganized. occasionally perivascular lymphocytic infiltrates or deep dermal plasma cells are noted.1 the differential diagnosis of nl includes granuloma annulare, necrobiotic xanthogranuloma, and cutaneous sarcoidosis. granuloma annulare is distinguished by interstitial histiocytes with or without perivascular lymphocytic infiltrate and/or focal organization about dermal mucin. biopsy of necrobiotic xanthogranuloma may reveal dermal necrosis surrounded by palisading histiocytes with giant cells. finally, cutaneous sarcoidosis should be suspected if circumscribed islands of epithelioid cells with rare giant cells and minimal to absent fibrin necrobiosis lipoidica (nl) is a rare, granulomatous skin disease with a predilection for diabetic patients. nl can present both histopathologically and clinically in a similar fashion to other granulomatous dermatoses such as granuloma annulare, necrobiotic xanthogranuloma, and cutaneous sarcoidosis. when nl is suspected in patients without glucose intolerance, affirmative diagnosis can be difficult, and other comorbidities may be probed, as nl has been associated with conditions such as hypertension, dyslipidemia, and thyroid disorders. familial disease has also been reported. in the following case report, we discuss a 15-year-old girl who presented with a new, single, pink atrophic plaque of the right pretibial region. biopsy showed palisaded granulomatous inflammation within the dermis, absent dermal mucin, and rare multinucleated giant cells. this histopathologic description combined with the clinical context led to the diagnosis of necrobiosis lipoidica. the patient developed another similar lesion on the left anterior shin over the next 1.5 years which was also diagnosed as necrobiosis lipoidica. the lesions were treated with intralesional triamcinolone acetonide and topical tacrolimus. both lesions are now resolved with only mild atrophy of the affected areas. to date, the patient’s labs have shown no evidence of glucose intolerance, hyperlipidemia, or thyroid disorder. abstract introduction skin may 2019 volume 3 issue 3 copyright 2018 the national society for cutaneous medicine 220 figure 1: necrobiosis lipoidica. patient’s right anterior tibia at presentation (2014). are noted, especially in the context of asteroid or schaumann bodies.1 nl affects women twice as often as men and frequently presents in the sixth decade of life.2,3 up to 65% of nl is associated with diabetes mellitus, and the lesions can either indicate or precede the existence of disease, with 0.3% of diabetics affected in their lifetime.4 however, diabetes is not necessary for the existence of nl, as the disease has also been associated with other conditions such as hypertension and dyslipidemia.2 higher rates of thyroid disorders have also been noted in patients with nl than in the general population.5 lastly, nl can present in siblings with no evidence of diabetes, termed familial nondiabetic necrobiosis lipoidica.6 here, we detail the unusual case of a 15year-old girl who presented in 2014 with a new rash of the right anterior shin. the pretibial lesion was a single, unilateral, pink atrophic plaque with orange-brown red rolled borders (figure 1). biopsy of the lesion revealed palisaded granulomatous inflammation within the dermis, absent figure 2: necrobiosis lipoidica. histologic section of skin from right pretibial region at 40x (a) and 100x (b) stained by h&e. sections demonstrate a tiered focus of lymphohistiocytic inflammation within the mid to deep dermis. rare multinucleated giant cells are seen surrounding this area, which did not demonstrate mucin deposition on colloidal iron stain (not shown). interstitial mucin evaluated by colloidal iron stain, and rare multinucleated giant cells in the deeper aspects (figure 2). this histopathologic description combined with the clinical context, especially the lesion’s pretibial location, was consistent with necrobiosis lipoidica. other diagnoses such as granuloma annulare and cutaneous sarcoidosis were considered less suspect secondary to absent dermal mucin, present giant cells, lack of classic island formation, and no asteroid bodies. case report skin may 2019 volume 3 issue 3 copyright 2018 the national society for cutaneous medicine 221 subsequent to a diagnosis of necrobiosis lipoidica in the absence of preexisting diabetes, the patient was evaluated for other comorbidities, especially those associated with nl. the patient had no evidence of hypertension, obesity, or hyperlipidemia. pertinent lab values were: hemoglobin a1c 4.8% (nl 4.0-5.6), fasting glucose 71 mg/dl (nl 70-99), insulin 11.9 aiu/ml (nl 29.2), tsh 1.263 uiu/ml (nl 0.340-4.410), free t4 0.60 ng/dl (nl 0.61-1.12), free t3 3.2 pg/ml (nl 2.3-4.2), sedimentation rate 18 mm/hr (nl <20), and globulin gap 2.7 g/dl (nl 1.8-4.0). although the free thyroxine value was 0.01 ng/dl below the normal range for the test used, the patient had no clinical symptoms of hypothyroidism, had normal thyroid stimulating hormone and free triiodothyronine levels, and lacked thyroglobulin or thyroid peroxidase antibodies. thus, the finding was considered clinically insignificant, and the patient is not on thyroid hormone replacement therapy. additionally, the patient had no family history of nl, diabetes, or other autoimmune diseases like celiac disease, rheumatoid arthritis, or systemic lupus erythematosus. over the next 1.5 years, the patient developed an additional small nl lesion on the left anterior shin. both lesions were treated with intralesional triamcinolone acetonide in clinic, and the patient was instructed to apply tacrolimus 0.1% topical ointment twice daily at the initiation of treatment, tapered to twice weekly by the end. the right shin lesion was treated at three separate visits with intralesional triamcinolone acetonide. doses varied to maximize therapeutic value while minimizing atrophy as lesions were responding to treatment. at ten days after presentation, the lesion was treated with 4.8 mg triamcinolone acetonide, at one month with 9.0 mg, and at four months with 1.5 mg. the left shin was treated once with 1.5 mg triamcinolone figure 3: necrobiosis lipoidica. patient’s legs 2.5 years after diagnosis (2016). acetonide. both lesions are now resolved with only mild atrophy of the affected areas (figure 3). the patient is pleased with the cosmetic result. this case demonstrates the appropriateness of keeping necrobiosis lipoidica in the differential diagnosis for patients presenting with plaques or ulcerating lesions, especially of the pretibial area, even with no associated comorbidities and/or uncommon histopathology. treatment regimens for nl are largely based on case reports and uncontrolled studies, and published epidemiologic statistics vary widely, suggesting avenues for future research. while some patients forego medical therapy, the patient described here elected to pursue treatment with intralesional corticosteroids and topical tacrolimus. we believe prompt biopsy and diagnosis, close follow-up, and targeted intralesional therapy allowed the patient to experience minimal atrophy and complete resolution of her lesions. discussion skin may 2019 volume 3 issue 3 copyright 2018 the national society for cutaneous medicine 222 conflict of interest disclosures: none. funding: none. acknowledgements: the authors would like to thank robert m. law, md, who assisted with dermatopathologic analysis and photomicrographs for this case. corresponding author: allison l limmer, bs, ba mcgovern medical school at uthealth houston, tx allison.l.limmer@uth.tmc.edu references: 1. ko cj, glusac ej. chapter 14: noninfectious granulomas. in: elder de. lever’s histopathology of the skin. 11th ed. philadelphia, pa: wolters kluwer; 2015:427-57. 2. jockenhöfer f, kröger k, klode j, renner r, erfurt-berge c, dissemond j. cofactors and comorbidities of necrobiosis lipoidica: analysis of the german drg data from 2012. j dtsch dermatol ges 2016;14:277-84. 3. reid sd, ladizinski b, lee k, baibergenova a, alavi a. update on necrobiosis lipoidica: a review of etiology, diagnosis, and treatment options. j am acad dermatol 2013;69:783-91. 4. muller sa, winkelmann rk. necrobiosis lipoidica diabeticorum. a clinical and pathological investigation of 171 cases. arch dermatol 1966;93:272-81. 5. erfurt-berge c, dissemond j, schwede k et al. updated results of 100 patients on clinical features and therapeutic options in necrobiosis lipoidica in a retrospective multicentre study. eur j dermatol 2015;25:595-601. 6. ho kk, o’loughlin s, powell fc. familial non-diabetic necrobiosis lipoidica. australas j dermatol 1992;33:31-4. mailto:allison.l.limmer@uth.tmc.edu skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 75 short communications imatinib-induced acquired dermal melanocytosis anna eversman, bs1, sakeena fatima, md2, kord s. honda, md1,2, mara g. beveridge, md1,2 1case western reserve university school of medicine, cleveland, oh 2university hospitals cleveland medical center, department of dermatology, cleveland, oh imatinib, a tyrosine kinase inhibitor, is commonly used to treat gastrointestinal stromal tumors and hematologic malignancies.1 cutaneous reactions occur in up to 69% of patients, most commonly manifesting as superficial edema and an exanthem-like rash.2 recent literature documents changes in pigmentation, with higher rates of hypopigmentation (40.9%) as compared to hyperpigmentation (3.6%).3 while the histologic appearance of imatinibinduced hyperpigmentation varies, intradermal hemosiderosis is the most common finding.4 we report a rare case of hyperpigmented patches secondary to dermal melanocytosis following imatinib treatment in an african american patient with acute lymphoblastic leukemia (all). an 81-year-old african american woman with a history of all presented to dermatology clinic with diffuse hyperpigmented patches of her face, upper back, and shoulders in february of 2020. she was initially diagnosed with all in august of 2014, and complete remission was achieved shortly thereafter with 2 cycles of hyper-cvad (cyclophosphamide, vincristine, doxorubicin, and dexamethasone) and initiation of imatinib therapy. at the time of presentation, imatinib use had been continuous for more than 5 years. physical examination revealed diffuse, ill-defined, slate-grey hyperpigmented patches distributed symmetrically on the bilateral temples, forehead, upper back, and shoulders. hyperpigmented patches of her face were first observed in september of 2015, with abstract background: imatinib, a tyrosine kinase inhibitor, is commonly used to treat gastrointestinal stromal tumors and hematologic malignancies. hyperpigmentation is a known side-effect of imatinib, with intradermal hemosiderosis being the most common histologic finding. case presentation: we report a rare case of hyperpigmentation secondary to dermal melanocytosis following imatinib treatment in an african american patient with acute lymphoblastic leukemia. conclusion: the efficacy of imatinib and the benign nature of the pigment abnormalities should be emphasized to prevent unnecessary treatment cessation in patients presenting with imatinib-induced dermal melanocytosis. introduction case presentation skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 76 figure 1. clinical examination showed ill-defined, slate-grey hyperp igmentation of (a) forehead, (b) temples, (c) and upper back. later expansion to her shoulders and neck. a punch biopsy of the right shoulder was obtained, revealing occasional pigmented spindled cells in the superficial and deep reticular dermis. an iron stain was negative. the pigment stained positive with fontanamasson and the cells stained with antibodies against melan-a. a final diagnosis of dermal melanocytosis was made. given the patient’s positive response to imatinib, the favorable side effect profile of imatinib compared to other tyrosine kinase inhibitors, and the benign nature of the pigmentation abnormalities, she remains on imatinib. imatinib has been known to induce dyspigmentation. 5 although imatinibinduced hypopigmentation has been attributed to inhibition of the c-kit/scf pathway which is responsible for the differentiation, survival, and proliferation of melanocytes, the mechanism of paradoxical imatinib-induced hyperpigmentation is unclear and the histologic findings are diverse.1 among patients with imatinibinduced hyperpigmentation, intradermal hemosiderosis is the most common finding on biopsy.4 the pathophysiology involves damage to the dermal vessels and subsequent deposition of iron in the skin. as later development of hepatic hemosiderosis has been reported, these patients should be closely monitored for signs of liver disease.6 rarely, imatinib-induced hyperpigmentation has been attributed to dermal melanocytosis. kok et al reported 3 cases of generalized hypopigmentation and progression of existing dermal melanocytosis.7 although dermal melanocytosis appears bluish-grey and the pigmentation of intradermal hemosiderosis is classically dark brown, color changes vary and can be difficult to distinguish clinically. biopsy is therefore essential to ensure appropriate diagnosis and subsequent management. although dermal melanocytosis is evidence of melanocyte activation, there are only 5 reported cases of primary cutaneous discussion a. b. c. skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 77 figure 2. histopathologic examination revealed (a) heavily-pigmented superficial spindled cells in the dermis (h&e, 40x). (b) fontana-masson staining showed spindled melanocytes in the dermis (40x). melanoma arising in the context of acquired dermal melanocytosis.8,9 the precursor lesion was a nevus of ota in all 5 of these cases, in contrast to our patient.9 furthermore, imatinib may offer a protective benefit as it inhibits the c-kit/scf pathway and has been used in the treatment of melanoma with kit mutations.10,11 for these reasons, we are doubtful our patient’s dermal melanocytosis confers an increased risk of melanoma, although there is a lack of literature regarding this topic. the efficacy of imatinib and the benign nature of the pigment abnormalities should be emphasized to prevent unnecessary treatment cessation in patients presenting with imatinib-induced dermal melanocytosis. conflict of interest disclosures: none funding: none corresponding author: mara beveridge, md 2109 adelbert road cleveland, oh 44016 phone: 216-514-8630 email: mara.beveridge@uhhospitals.org references: 1. verma d, kantarjian h, strom ss, rios mb, jabbour e, quintas-cardama a, et al. malignancies occurring during therapy with tyrosine kinase inhibitors (tkis) for chronic myeloid leukemia (cml) and other hematologic malignancies. blood. 2011;118:4353–4358. 2. scheinfeld n. imatinib mesylate and dermatology part 2: a review of the cutaneous side effects of imatinib mesylate. j drugs dermatol 2006;5:228–231. 3. arora b, kumar l, sharma a, wadhwa j, kochupillai v. pigmentary changes in chronic myeloid leukemia patients treated with imatinib mesylate. ann oncol 2004;15:358-9. 4. pureesrisak p, tienthavorn t. imatinib mesylate induced acquired dermal melanocytosis: a rare case report. thai journal of dermatology. 2017; 33(4): 297-305. 5. grichnik jm, burch ja, burchette j, shea cr. the scf/kit pathway plays a critical role in the control of normal human melanocyte homeostasis. j invest dermatol 1998;111:233-8. 6. maiti b, setrakian s, daw ha. hepatic iron overload, a possible consequence of treatment with imatinib mesylate: a case report. cases j. 2009; 2:7526. 7. kok wl, chen q, lee ssj, chua sh, ng sk. a case series of imatinib-induced generalized hypopigmentation and progression of existing acquired dermal melanocytosis. j dermatolog treat. 2017;28(8):762–3. 8. baykal c, yılmaz z, sun gp, büyükbabani n. the spectrum of benign dermal dendritic melanocytic proliferations. j eur acad dermatol venereol. 2019;33(6):1029-1041. 9. tse jy, walls be, pomerantz h, yoon ch, et al. melanoma arising in a nevus of ito: novel genetic mutations and a review of the literature on cutaneous malignant transformation of dermal melanocytosis. j cutan pathol. 2016;43(1):57-63. 10. curtin ja, busam k, pinkel d, bastian bc. somatic activation of kit in distinct subtypes of melanoma. j clin oncol. 2006;24(26):4340-6. 11. hodi fs, corless cl, giobbie-hurder a, et al. imatinib for melanomas harboring mutationally activated or amplified kit arising on mucosal, acral, and chronically sundamaged skin. j clin oncol. 2013;31(26):3182-90. a. b. synopsis facial redness is a common, difficult to control cosmetic problem representing various phases of rosacea. using antiinflammatory/antioxidant botanicals in moisturizer formulations is a possible approach to minimizing the erythema. this research utilized a common facial cleanser, but only applied the botanically based moisturizer to one half face to properly assess efficacy. 30 female subjects fitzpatrick skin types i-iv 30-55 years of age with mild to moderate chronic facial redness, defined as a redness score of 3-6 on a 10-point scale, were enrolled. by the end of week 4, statistically significant improvement was seen on the cleanser/mask treated side in scaling (p<0.001), flaking (p<0.001), tactile smoothness (p<0.001), textural smoothness (p<0.001), firmness (p<0.001), radiance (p<0.001), luminosity (p<0.001), and overall appearance (p<0.001). thus, cosmetic moisturizers may be useful in reducing facial redness. objective the objective of this research was to examine the moisturizing and redness reducing effect of an anti-inflammatory botanical calm and repair night mask plus sulfate free foaming oil cleanser in subjects with mild to moderate facial redness. methods 30 female subjects fitzpatrick skin types i-iv and 30-55 years of age with mild to moderate chronic facial redness, defined as a redness score of 3-6 on a 10 point scale, were enrolled in this single-site split face study. subjects applied the cleanser to the entire face (skinfix foaming oil cleanser) and were randomized to apply a dime-sized amount of the study mask (skinfix calm & repair sleeping mask) only to one side of the face at bedtime, leaving the untreated side as a control. every attempt was made to enroll subjects with symmetrical facial redness to insure the validity of the results. the blinded dermatologist investigator visually assessed by the subjects for the following efficacy criteria on a 10-point scale (0=none to 9=extremely severe): erythema, capillaries, blotchiness, scaling, flaking, tactile smoothness, textural smoothness, firmness, radiance, luminosity, and overall appearance. each side of the face was separately assessed to allow each subject to act as their own control. the investigator also assessed product tolerability. photography, corneometry, and d-squames were performed. subjects were evaluated at baseline, immediately post-application, 1 day, 1week, and 4 weeks. results investigator assessments at day 1, there was statistically significant improvement in tactile smoothness (p=0.002) and textural smoothness (p=<0.001) in the botanical anti-inflammatory cleanser/mask treated facial side as compared to the cleanser only side (figure 1). the cleanser alone control showed improvement after 1 week of use in scaling (p=0.027), flaking (p=0.040), tactile smoothness (p=0.012) and textural smoothness (p= 0.027)(figure 2). the improvement continued into week 4. cleanser mildness was due to the sulfate-free formulation, which was created by excluding sodium lauryl sulfate and sodium laureth sulfate. by the end of week 4, statistically significant improvement was seen on the cleanser/mask treated side in scaling (p<0.001), flaking (p<0.001), tactile smoothness (p<0.001), textural smoothness (p<0.001), firmness (p<0.001), radiance (p<0.001), luminosity (p<0.001), and overall appearance (p<0.001). thus, the addition of the anti-inflammatory botanical night mask to the cleanser resulted in additive improvement, as demonstrated in figure 3. finally, figure 4 photographically demonstrates the results obtained with the cleanser/mask combination as compared to the cleanser alone. corneometry the corneometry measured the amount of water present in the skin as change from baseline. immediately after application, the skin hydration on the randomized mask applied facial side was statistically significantly superior (p<0.001) to the nontreated side of the face by 78% at day 1. this superior hydration due to the moisturizer and cleanser continued into week 1 (p=0.002) and week 4 (p=0.004) over the cleanser only side of the face. d-squames the d-squame was a piece of tape placed on the upper cheek on both sides of the face for exfoliation analysis. both sides of the face showed a reduction in skin scale of 9% at week 1 and the cleanser/mask side showed 11% reduction at week 4 while the cleanser side only showed a reduction in skin scale of 12%. thus, both the cleanser and the mask were effective in reducing retained skin scale. conclusion the anti-inflammatory botanically based night time mask and cleanser provided excellent moisturization, minimized barrier damage and facial redness. this combination demonstrated no tolerability or safety issues in a challenging population of females with mild to moderate facial erythema. the effect of an anti-inflammatory botanical cleanser/ night mask combination on facial redness reduction zoe diana draelos, md, dermatology consulting services, pllc, high point, north carolina zoe diana draelos, md, received a grant from skinfix to conduct the research presented in this poster. the material in this poster was previously published in the journal of drugs in dermatology. 20 15 10 5 0 cleanser cleanser + mask erythema textural smoothness firmnessblotchiness tactile smoothness radiance luminosity overallcapillaries scaling flaking foaming oil cleanser + calm and repair sleeping mask day 1 investigator e�cacy assessment: mean change from baseline within and between the regimen and cleanser only groups # * ** 40 30 20 10 0 cleanser cleanser + mask erythema textural smoothness firmnessblotchiness tactile smoothness radiance luminosity overallcapillaries scaling flaking foaming oil cleanser + calm and repair sleeping mask week 1 investigator e cacy assessment: mean change from baseline within and between the regimen and cleanser only groups # # # # # * * * * * * * # # # # # # 60 45 30 15 0 cleanser cleanser + mask foaming oil cleanser + calm and repair sleeping mask week 4 investigator e cacy assessment: mean change from baseline within and between the regimen and cleanser only groups erythema textural smoothness firmnessblotchiness tactile smoothness radiance luminosity overallcapillaries scaling flaking * * * * * * * * * * * * * * * * * # # # # # # # # foaming oil cleanser + calm and repair sleeping mask results representative photograph taken with cross-polarized light demonstrating the redness reduction with the cleanser + mask combination   day 1 investigator efficacy assessment mean change from baseline within and between the regimen and cleanser only groups. week 1 investigator efficacy assessment mean change from baseline within and between the regimen and cleanser only groups. week 4 investigator efficacy assessment mean change from baseline within and between the regimen and cleanser only groups. treated & untreated cleanser cleanser cleanser cleanser + mask cleanser + mask cleanser + mask controlcleanser + mask representative photograph taken with cross-polarized light demonstrating the redness reduction with the cleanser + mask combination 4% 5% 2% 3% 2% 1% 7% 8% 6% 9% 11% 21% 10% 21% skin improvement occured eariler with the combined anti-inflammatory night mask and cleanser 7% 9% 0% 4% 1% 4% 14% 39% 15% 38% 17% 36% 15% 36% 2% 4% 16% 4% 16% 3% 19% 20% 25% 13% 19% 11% 16% 23% 60% 23% 59% 21% 51% 20% 51% -2% 14% -2% 6% 27% 6% 27% 6% 25% the addition of the anti-inflammatory botanical night mask to the cleanser resulted in additive improvement. skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 118 resident competition research article the differential impact of covid-19 on urban versus rural dermatologic practice logistics and recovery: a cross-sectional investigation of the first wave justin w. marson, md1, graham h. litchman, do, ms2, darrell s. rigel, md, ms3 1national society for cutaneous medicine, new york, ny 2department of dermatology, st. john’s episcopal hospital, new york, ny 3department of dermatology, nyu grossman school of medicine, new york, ny the covid-19 pandemic has significantly affected clinical practice worldwide.1,2 however, the degree to which us regions and therefore local healthcare systems were affected varied during the initial pandemic.3 the purpose of this study was to determine the covid-19 pandemic’s differential impact on dermatologic outpatient care in urban versus rural areas in the united states. abstract background: covid-19 materially delayed patient visits and potential skin cancer biopsies/diagnoses among us dermatology practices. however, given a likely heterogenous impact across the us, this study sought to determine covid-19’s effect on urban versus rural dermatology practices. methods: data were analyzed from the first 1000 responses to 3 pre-validated surveys of 9891 practicing us dermatologists comparing outpatient volumes and scheduling issues for the week of february 17th to the week of march 16th (survey 1), april 13th (survey 2) and may 18th, 2020 (survey 3). first 3 us zip-code digits were compared to us census bureau data to determine “urban/rural” status. representativeness with aad membership was confirmed. statistical significance was calculated using chi-square with marascuilo procedure and two-tailed independent t-test/anova with post-hoc tukey-kramer testing. results: in april 2020 urban practices reported more closed practices (21.4% vs 5.8%, p<0.0001) and predicted significantly larger patient volume decreases (-45.2% vs -31.4%, p<0.0001) and practice closures (11.9% vs. 2.5% p<0.0001) in the following 2 weeks. in may 2020, urban areas saw significantly fewer patients/week (90.9 vs 142.4 p<0.0001), larger decrease in patient volume relative to may 2019 (-49.4% vs -35.1%, p<0.0001), and conducted more telemedicine visits (27.0% vs 15.1%, p<0.0001). significantly more rural practices reported already being at baseline volume (mean difference 6.2%, 95% ci 2.7%-9.8%) while urban practices predicted return to baseline volume by august (5.7, 95% ci 2.1%-9.3%) or were unsure (5.6, 95% ci 1.6%-9.7%). conclusion: the initial covid-19 pandemic differentially affected urban dermatology practices. the effects of the pandemic were mitigated in part by increased use telemedicine. future studies may further elucidate covid-19’s effect on clinical practice and highlight areas for improvement in practice logistics and patient care. introduction skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 119 data were analyzed from the first 1000 responses to 3 pre-validated surveys of 9891 practicing us dermatologists collected for the week of february 17th, march 16th (survey 1), april 13th (survey 2) and may 18th, 2020 (survey 3). results compared outpatient volumes and scheduling issues between these time points. the first 3 digits of us zip codes (section code) were compared to us census bureau data4 to determine “urban/rural” status. section codes containing counties with both designations were assigned based on predominate designation within that region. representativeness with aad membership was confirmed with 95% confidence intervals (ci) (tables 1,2). statistical significance was calculated using chi-square with marascuilo procedure for categorical data and two-tailed independent t-test with unequal variance/anova with post-hoc tukey-kramer testing for continuous data. there were significantly more urban respondents in regions with section codes beginning with 1,8 and 9 and more rural in regions 2,4, and 5 (table 1). practice mix/type was similar between urban/rural practices and across surveys (table 2). in april 2020 urban practices predicted significantly larger patient volume decreases over the next 2 weeks(-45.2%; 95%ci -47.9 to -42.4 vs -31.4%; 95%ci -37.9 to -24.9, p<0.0001), and practice closures in the following 2 weeks(11.9%; 9.7% 14.1% vs 2.5%; 0.0% 5.4%, p<0.0001) and reported more closed practices (21.4%;18.6%-24.1% vs 5.8%;1.6%-10.1%,p<0.0001) (table 3). urban practices also obtained fewer biopsies of suspicious-pigmented lesions (2.7;2.4-3.1 vs 4.8;3.4-6.2) however this finding only trended towards significance after post-hoc testing. in may 2020, both urban and rural practices predicted similar increases in practice volume. however, urban areas saw significantly fewer patients/week (90.9; 81.6 100.2 vs 142.4; 105.0-179.8, p<0.0001) and larger decreases in patient volume relative to may 2019(-49.4%;-51.2% to 47.6% vs -35.1%; -39.6% to -30.6%, p<0.0001). furthermore, a significantly larger proportion of rural practices reported being already back to baseline volume compared to urban practices (mean difference 6.2%, 2.7%-9.8%). urban practices had a median predicted to baseline patient volumes by august (5.7%, 2.1%-9.3%) or were unsure (5.6%, 1.6%9.7%) (table 4). urban practices conducted a significantly higher percentage of visits via telemedicine (27.0%; 24.7% 29.3% vs 15.1%; 10.3% 19.8%, p<0.0001). urban areas also predicted a higher percentage of telemedicine usage in june 2020 (21.8%; 19.9% 23.7% vs 12.2%; 9.1% 15.4%). the initial covid-19 pandemic had a heterogeneous impact on dermatologic practices, wherein urban practices experienced significantly more practice losses and a slower recovery. these results suggest “hot-spots” likely played a larger role than dermatology density in modulating relative impact as more heavily populated/urban areas had more active cases and generally stricter governmental/institutional regulations earlier in the pandemic.3,5 the recovery pattern methods results discussion skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 120 table 1. geographic representation by urban/rural designation compared to aad membership data. per survey, overall regional demographics congruent with national data. notably, increased proportions of respondents from urban areas in regions 1,8 and 9 while there were increased proportions of dermatologists in rural areas in regions 2,4 and 5. survey 1 % (95%ci) survey 2 % (95%ci) survey 3 % (95%ci) p-value % aad us membership overall urban (n = 847) rural (n = 118) overall urban (n = 875) rural (n = 120) overall urban (n = 742) rural (n = 87) 9.6 9.4 (7.5-11.3) 9.9 (7.9-12.0) 5.9 (1.6-10.3) 8.4 (6.6-10.2) 9.3 (7.3-11.2) 2.5*‡ (0.0-5.4) 9.8 (7.7-11.9) 10.1 (7.9-12.3) 8.2 (2.3-14.2) 0.1524 12.8 14.0 (11.8-16.2) 15.7 (13.2-18.2) 2.5*‡ (0.00-5.4) 15.8 (13.5-18.1) 17.0 (14.5-19.6) 7.5 (2.7-12.3) 17.5 (14.9-20.1) 18.4‡ (15.5-21.2) 11.8 (4.8-18.8) <0.0001 10.4 11.0 (9.0-12.9) 9.2* (7.2-11.2) 24.6‡ (16.6-32.5) 10.9 (8.9-12.9) 8.9* (7.0-10.8) 25.8‡ (17.8-33.8) 8.9 (6.9-10.9) 7.3 (5.4-9.2) 23.5 (14.3-32.7) <0.0001 13.8 12.3 (10.2-14.4) 12.4 (10.1-14.7) 11.9 (5.9-17.8) 12.4 (10.3-14.5) 12.0 (9.8-14.2) 15.8 (9.1-22.5) 11.5 (9.3-13.7) 11.3 (9.0-13.7) 14.1 (6.6-21.7) 0.3030 8.4 7.6 (5.9-9.3) 7.0 (5.2-8.7) 12.7 (6.6-18.8) 8.6 (6.8-10.4) 7.9 (6.0-9.7) 14.2 (7.8-20.5) 6.3 (4.6-8.0) 5.8 (4.1-7.5) 11.8 (4.8-18.8) 0.0056 5.0 3.9 (2.7-5.1) 3.1 (1.9-4.3) 10.2 (4.6-15.7) 4.2 (2.9-5.5) 3.4 (2.2-4.7) 10.0 (4.5-15.4) 3.7 (2.4-5.0) 3.2 (1.9-4.5) 8.2 (2.3-14.2) <0.0001 6.5 6.6 (5.0-8.2) 6.5 (4.8-8.2) 7.6 (2.7-12.5) 6.2 (4.7-7.7) 6.3 (4.6-7.9) 5.8 (1.6-10.1) 6.6 (4.9-8.3) 5.9 (4.2-7.7) 12.9 (5.7-20.2) 0.3594 10.0 10.0 (8.1-11.9) 9.3 (7.3-11.3) 14.4 (7.9-20.9) 8.7 (6.9-10.5) 8.7 (6.8-10.6) 9.2 (3.9-14.4) 9.9 (7.8-12.0) 10.8 (8.5-13.1) 3.5 (0.0-7.5) 0.1658 6.2 8.4 (6.6-10.2) 8.9 (6.9-10.8) 5.1 (1.0-9.1) 7.7 (6.0-9.4) 8.0 (6.2-9.8) 5.8 (1.6-10.1) 6.6 (4.9-8.3) 6.9 (5.0-8.7) 3.5 (0.0-7.5) 0.0262 17.3 16.3 (13.9-18.7) 18.1 (15.4-20.7) 5.1*‡ (1.0-9.1) 16.5 (14.2-18.8) 18.5 (15.9-21.1) 3.3*‡ (0.1-6.6) 18.2 (15.5-20.9) 20.2 (17.3-23.2) 2.4*‡ (0.0-5.6) <0.0001 *significantly less than corresponding value from same survey, p<0.05 ‡significantly different from aad membership data 95% ci – 95% confidence interval skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 121 table 2. practice demographics comparing urban and rural respondents to national data. across surveys, similar practice type and levels of experience. increased urban respondents reporting cosmetic practice compared to rural likely reflecting increased demand as well as natural increase in cosmetic practice since 2014. *source: american academy of dermatology. practices mix/types not available. **source: margosian e. medical vs. cosmetic dermatology: who is doing what?. dermatology world.2019. http://digitaleditions.walsworthprintgroup.com/publication/?m=12468&i=552514&view=articlebrowser&article_id=3267519&search=practice%20profile&ver=html5. no data available for dermatopathology 95% ci – 95% confidence interval demographics survey 1 survey 2 survey 3 aad membership urban rural urban rural urban rural practice type %(95%ci) private 88.5 (86.5-90.7) 92.4 (87.5-97.3) 89.1 (87.0-91.2) 93.3 (88.8-97.9) 89.7 (87.5-92.0) 90.6 (84.2-96.9) university/academic/ government 11.5 (9.3-13.6) 7.6 (2.7-12.5) 10.9 (8.8-13.0) 6.7 (2.1-11.2) 10.3 (8.0-12.5) 9.4 (3.1-15.7) years of experience %(95%ci) 1-10 21.6 (18.8-24.4) 20.3 (12.9-27.7) 18.5 (15.9-21.1) 21.7 (14.1-29.2) 15.0 (12.4-17.6) 24.7 (15.3-34.1) 27.0% 11-20 26.0 (23.0-29.0) 32.2 (23.6-40.8) 25.1 (22.2-28.1) 30.8 (22.3-39.3) 22.3 (19.2-25.3) 25.8 (16.4-35.4) 27.5% 21-30 26.8 (23.8-29.8) 23.7 (15.9-31.6) 29.8 (26.7-32.9) 25.8 (17.8-33.8) 30.1 (26.7-33.5) 27.1 (17.4-36.7) 21.8% >30 25.6 (22.6-28.6) 23.7 (15.9-31.6) 26.5 (23.5-29.5) 21.7 (14.1-29.2) 32.7 (29.2-36.1) 22.4 (13.3-31.4) 23.7% practice mix %(95%ci) aad practice profile 2017 medical 62.8 (61.2-64.4) 64.5 (60.7-68.3) 60.0 (58.3-61.8) 62.2 (58.0-66.4) 61.2 (59.5-63.0) 62.8 (57.4-68.3) 63% surgical/oncology 26.3 (24.7-27.9) 30.2 (26.5-34.0) 25.6 (23.9-27.4) 27.4 (23.2-31.6) 22.8 (21.0-24.5) 27.9 (22.5-33.4) 25% cosmetic 15.5 (13.9-43.3) 9.8 (6.0-21.9) 12.0 (10.2-32.3) 8.0 (3.7-15.5) 13.6 (11.8-37.3) 7.0 (1.6-10.2) 12% dermatopathology 4.9 (3.3-6.5) 1.6 (0.0-5.4) 2.4 (0.6-4.1) 2.4 (0.0-6.7) 2.4 (0.6-4.1) 2.2 (0.0-7.6) skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 122 table 3. retrospective (from february to may 2020) and prospective impact of covid-19 pandemic on dermatologic practices. urban practices had significantly larger decreases in patient volume and were more likely to be closed during the height of the initial pandemic and saw significantly less patients even as practices began to reopen. urban practices reporting significantly more sustained use of telemedicine than rural practice as practices reopened and adapted to new operating procedures. week of february 17, 2020 week of march 16, 2020 week of april 13, 2020 week of may 18, 2020 p-value* how many days did you practice? (mean; 95%ci) rural 4.2 (4.0-4.4) 3.4a (3.0-3.7) 3.5a (3.3-3.8) 3.9 (3.7-4.2) <0.0001 urban 4.2 (4.1-4.3) 3.0a (2.9-3.2) 3.5a,b (3.4-3.6) 3.6a,b (3.5-3.7) how many patients were seen in your primary practice location? (mean; 95%ci) rural 171.3 (139.5-203.1) 85.5a (68.4-102.5) 40.0a (29.4-50.5) 142.4b,c (105.0-179.8) <0.0001 urban 146.6 (135.9-157.2) 60.5a (54.5-66.5) 26.6a,b (23.3-30.0) 90.9a,b,c,d (81.6-100.2) how many biopsies did you perform for suspicious pigmented skin lesions? (mean; 95%ci) rural 20.1 (14.2-25.9) 10.5a (6.4-14.5) 4.8a (3.4-6.2) 11.9a (7.4-16.4) <0.0001 urban 19.8 (17.9-21.8) 7.4a (6.4-8.4) 2.7a,b (2.4-3.1) 7.4a,c (6.6-8.2) did you selectively postpone nonessential appointments? (%yes; 95%ci) rural 32.3 (22.7-39.7) 68.4a (57.8-79.1) 95.8a,b (92.2-99.5) 68.2a,c (58.1-78.3) <0.0001 urban 35.9 (32.1-39.7) 80.8a (77.4-84.1) 100.0a,b - 74.2a,c (71.0-77.4) how many biopsies were postponed? (mean; 95%ci) rural 3.4 (1.4-5.4) 10.2 (4.9-15.5) 7.5 (4.8-10.2) 3.8 (1.1-6.6) <0.0001 urban 4.0 (3.1-4.9) 10.8 a (9.2-12.4) 7.9a,b (6.8-9.0) 3.7b,c (2.8-4.5) prospective estimates march 16-20 april 13-18 may 18-23 p-value** if appointments were postponed during the week, when did you primarily reschedule them? weeks postponed (mean; 95%ci) rural 5.5 (4.3-6.6) 8.1b (7.4-8.7) 4.8c (3.9-5.8) <0.0001 urban 6.5 (6.1-6.8) 7.5b (7.2-7.7) 4.4b,c (4.2-4.7) % not rescheduled at this time (%; 95%ci) rural 18.7% (0.7%-27.7%) 19.3% (21.1%-26.6%) 13.1% (5.7%-20.5%) <0.0001 urban 26.7% (23.0%-30.5%) 19.3% (12.1%-26.6%) 10.7%b,c (8.4%-12.9%) if biopsies were postponed when did you primarily reschedule them? weeks postponed (mean; 95%ci) rural 7.0 (6.1-7.9) 6.5 (6.0-7.1) 1.5b,c (0.9-2.1) <0.0001 urban 7.2 (6.9-7.5) 6.3b (6.1-6.6) 2.0b,c (1.8-2.2) skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 123 % not rescheduled at this time (%; 95%ci) rural 65.3 (54.3-76.3) 42.5 (33.5-51.5) 7.1b,c (1.5-12.6) <0.0001 urban 53.8 (49.6-58.1) 36.5b (33.2-39.7) 8.8b,c (6.7-10.9) relative to your practice volume this week, what do you anticipate your schedule for the next 2 weeks will look like? (mean %; 95%ci) %change rural -58.3 (-64.9 to -51.7) -31.4b (-37.9 to -24.9) 17.5b,c (8.5 to 26.6) <0.0001 urban -57.3 (-60.1 to -54.5) -45.2b,d (-47.9 to -42.4) 13.0b,c (9.6 to 16.3) “completely closing practice” rural 7.9 (1.7-14.1) 2.5 (0.0-5.4) 2.4 (0.0-5.6) <0.0001 urban 20.3 (16.9-23.8) 11.9b,d (9.7-14.1) 3.0b,c (1.7-4.2) what was your patient volume this week compared to a typical april (survey 2) or may (survey 3) week in your practice? (mean %; 95%ci) % decrease rural -68.1 (-72.1 to -64.0) -35.1c (-39.6 to -30.6) <0.0001 urban -71.9 (-73.4 to -70.4) -49.4c,d (-51.2 to -47.6) “i was closed this week” rural 5.8 (1.6-10.1) 3.5 (0.0-7.5) <0.0001 urban 21.4d (18.6-24.1) 8.1c (6.1-10.1) what percentage of appointments did you do using telemedicine (0100%)? (mean %; 95%ci) rural 42.1 (35.5-48.7) 15.1c (10.3-19.8) <0.0001 urban 49.5 (46.8-52.2) 27.0c,d (24.7-29.3) in the next month, what percentage of your patient visits will be done using telemedicine because of covd-19? (mean %; 95%ci) rural 29.9 (23.0-36.7) 41.3 (35.2-47.4) 12.2b,c (9.1-15.4) <0.0001 urban 38.9 (35.9-41.9) 46.5b (44.2-48.9) 21.8b,c (19.9-23.7) *p-value from anova, tukey-kramer calculated at α = 0.05 **p-value from anova or chi-square, tukey-kramer calculated at α = 0.05, marascuilo calculated at α 0.05 asignificantly different from february 2020 bsignificantly different from march 2020 csignificantly different from april 2020 dsignificantly different from value of the same date from rural/urban counterpart 95% ci – 95% confidence interval noted in urban areas may also reflect increased and continued use of telemedicine, which was nearly nonexistent prior to covid-19.6 limitations include retrospective estimations and “free-time” bias for dermatologists with significant decreases in patient volume. however, a consistent and sufficiently large sample size with responses restricted to a skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 124 window of time accounts for these biases. the study period captured a “snapshot” of covid-19’s impact on the us, during which time urban areas had more positive cases and regional covid-19 impact on recovery rates/clinical practice may parallel regional shifts in covid-19 caseloads. table 4. urban versus rural predictions for full reopening. significantly more rural practices are practicing at full capacity at time of survey (may 2020) compared to urban practices while a larger proportion of urban practices predict august or are unsure. urban % rural % mean % difference % (95% ci) when do you think your practice will return to baseline? already back to baseline 2.0 8.2 -6.2 (-9.8, -2.7)* june 7.3 9.4 -2.1 (-5.8, 1.5) july 11.5 15.3 -3.8 (-7.8, 0.1) august 13.9 8.2 5.7 (2.1, 9.3)* september 10.5 11.8 -1.2 (-5.0, 2.6) october 6.1 5.9 0.2 (-3.2, 3.5) november 2.4 1.2 1.3 (-1.1, 3.6) december 0.8 1.2 -0.4 (-2.7, 2.0) 1/2021 or beyond 16.3 15.3 1.0 (-2.9, 5.0) unsure 29.1 23.5 5.6 (1.6, 9.7)* *absolute value of mean difference > 0 95% ci – 95% confidence interval these findings demonstrate the significant and differential impact covid-19 had on urban versus rural dermatology practices. telemedicine has had a mitigating effect, and may continue to supplement patient volumes as practices recover. however, telemedicine’s role and further integration into practice post-pandemic remains uncertain. further studies may better elucidate the covid-19’s evolving impact on clinical practice in various practice settings. these results provide insight into disparities between practices and can potentially highlight areas for improvement in both practice logistics as well as patient care. conflict of interest disclosures: none funding: none corresponding author: justin w. marson, md national society for cutaneous medicine 35 e 35th st. #208 new york ny, 10016 email: justin.w.marson@gmail.com references: 1. litchman gh, rigel ds. the immediate impact of covid-19 on us dermatology practices. j am acad dermatol. 2020;83(2):685-686. doi:10.1016/j.jaad.2020.05.048 2. litchman gh, marson jw, rigel ds. the continuing impact of covid-19 on dermatology practice: office workflow, economics and future implications. j am acad dermatol. 2020 sep 30:s0190-9622(20)32658-x. doi: 10.1016/j.jaad.2020.08.131. epub ahead of print. pmid: 33010326; pmcid: pmc7526524. 3. america is reopening. but have we flattened the curve? johns hopkins university & medicine coronavirus resource center. https://coronavirus.jhu.edu/data/new-cases-50states 4. county rurality level 2010. us census bureau. www2.census.gov/reference/county_rural_look up. accessed 27 october 2020 5. glazer am, rigel ds. analysis of trends in geographic distribution of us dermatology workforce density. jama dermatol. 2017 may 1;153(5):472-473. doi: 10.1001/jamadermatol.2016.6032. pmid: 28296988; pmcid: pmc5470415. 6. ehrlich a, kostecki j, olkaba h. trends in dermatology practices and the implications for the workforce. j am acad dermatol. 2017;77(4):746-752. doi:10.1016/j.jaad.2017.06.030. conclusion mailto:justin.w.marson@gmail.com https://coronavirus.jhu.edu/data/new-cases-50-states https://coronavirus.jhu.edu/data/new-cases-50-states skin july 2019 volume 3 issue 4 copyright 2019 the national society for cutaneous medicine 250 research letter identifying changes in trends in the age standardized incidence of melanoma in australia david m hille, mph, md1 1royal perth hospital, perth, western australia, australia melanoma is a serious public health issue in australia.1 despite numerous awareness campaigns, such as the “slip! slop! slap!” and “sunsmart” campaigns, age standardized incidence of melanoma is steadily increasing.2,3 studies analysing trends in state specific age standardized incidence rates, have identified changes in the rate at which the annual incidence of invasive melanoma is increasing.4 decreases in incidence rates were identified in certain demographics.4 annual age-standardized data for the incidence of melanoma in australia is publicly available from the australian institute of health and welfare (aihw). cancer is a notifiable disease in australia.5 age standardized incidence for males, females, and all persons, between 1982 to 2015, was retrieved from the aihw. a twopiece piecewise linear regression was fitted to each data set. the piecewise breakpoint was varied through an iterative process. an optimal breakpoint was determined by maximizing adjusted r-squared. the breakpoint was assessed for statistical significance using chow’s test. statistical data analysis was performed in r (3.3.2). microsoft excel (15.32) was used to produce figures. for a breakpoint, yeart , a dummy variable, dt , is defined such that dt = 0 when year < yeart , and 1 otherwise. the piecewise regression equation then follows: incidence = b0 + b1 year + b2 dt + b3 dt year when year < yeart the equation reduces to: incidence = b0 + b1 year and, when year >= yeart the equation reduces to: incidence = b0 + b2 + (b1+ b3 ) year this method, therefore, determines if there is a single abrupt change in a trend over time. for age standardized incidence for all persons, the model maximized adjusted rsquared (adj-r2 = 0.95) at a breakpoint at 1998. this breakpoint is statistically significant (p < 0.001). the estimated gradient prior to the breakpoint (1.25; p < 0.001) is greater than the estimated gradient after the breakpoint (0.30; p < 0.001). in practical terms, this means that age-standardized incidence increases at a significantly smaller rate post-1998, but continues to rise. these findings are presented in figure 1. skin july 2019 volume 3 issue 4 copyright 2019 the national society for cutaneous medicine 251 figure 1: age standardized incidence of melanoma in australia for all persons. black circles represent the observed incidence between 1982 and 1997. the black dashed line is the estimated linear model for incidence between 1982 and 1997. purple circles represent the observed incidence between 1998 and 2015. the purple dashed line is the estimated linear model for incidence between 1998 and 2015. (data: aihw 2018) figure 2: age standardized incidence of melanoma in australia for males and females. black squares (triangles) represent the observed incidence for males (females) between 1982 and 1997 (2005). the black dashed (dotted) line is the estimated linear model for incidence for males (females) between 1982 and 1997 (2005). purple squares (triangles) represent the observed incidence for males (females) between 1998 (2006) and 2015. the purple dashed (dotted) line is the estimated linear model for incidence for males (females) between 1998 (2006) and 2015. (data: aihw 2018) for males, the optimal breakpoint is also at 1998 (adj-r2 = 0.97; p < 0.001). the estimated gradient prior to the breakpoint (1.84; p < 0.001) is greater than the estimated gradient after the breakpoint (0.44; p < 0.001). for females, the optimal breakpoint is also 2006 (adj-r2 = 0.88; p < 0.001). the estimated gradient prior to the breakpoint (0.57; p < 0.001) is greater than the estimated gradient after the breakpoint (0.31; p < 0.01). these findings are presented in figure 2. the key limitation of this study is that the data does not provide detail of thickness or stage of melanoma. trends in the age standardized incidence of thicker or higher staged melanoma would be useful because these factors correlate with prognosis. the observed incidence for new south wales for 2015 was not available at the time of compilation of dataset and was estimated by the aihw3,5. breakpoints in the trends of age standardized incidence of melanoma in australia have been identified for all persons, males, and females. for each group, the gradient of the trend decreased post-breakpoint, but remained positive. the reasons for this result are unclear. public health campaigns advocating sun protection have been in place since the nineteen-eighties.2 however, given the greater incidence of melanoma in older age groups, it is unlikely that population-level changes in sun exposure behavior could have translated into a tangible, and abrupt, change in incidence in the time frame between the initiation of those campaigns and the breakpoints identified in this letter. the analysis of age standardized incidence rate trends presented in this letter provides a useful starting point for further analysis of trends. it may also be a catalyst for researchers to consider factors affecting changes in incidence rates. further research is needed to appreciate the detail underlying the trends identified. specifically, it would be valuable to separate in situ melanoma from invasive melanoma. state specific analysis may also prove useful. 0 20 40 60 1980 1985 1990 1995 2000 2005 2010 2015 a g e s ta n d a rd iz e d i n ci d e n ce p e r 1 0 0 ,0 0 0 p e rs o n s year 0 20 40 60 80 1980 1985 1990 1995 2000 2005 2010 2015 a g e s ta n d a rd iz e d i n ci d e n ce p e r 1 0 0 ,0 0 0 p e rs o n s year skin july 2019 volume 3 issue 4 copyright 2019 the national society for cutaneous medicine 252 conflict of interest disclosures: none. funding: none. corresponding author: david m hille, mph, md royal perth hospital, perth, western australia, australia dmhille@gmail.com references 1. australian institute of health and welfare (aihw) 2017. cancer in australia 2017. cancer series no.101. cat. no. can 100. canberra: aihw. <https://www.aihw.gov.au/getmedia /3da1f3c2-30f0-4475-8aed1f19f8e16d48/20066-cancer2017.pdf.aspx?inline=true>. 2. iannacone mr, green ac. towards skin cancer prevention and early detection: evolution of skin cancer awareness campaigns in australia. melanoma management. 2014;1(1):75-84. 3. australian institute of health and welfare (aihw) 2018. cancer data in australia; australian cancer incidence and mortality (acim) books: melanoma of the skin canberra: aihw. <https://www.aihw.gov.au/reports/ cancer/cancer-data-in-australia/>. 4. curchin dj, harris vr, mccormack cj, smith sd. changing trends in the incidence of invasive melanoma in victoria, 1985–2015. medical journal of australia. 2018;208(6):265-269. 5. australian institute of health and welfare (aihw) 2017. australian cancer database, 2014; quality statement. canberra: aihw. <https://meteor.aihw.gov.au/conten t/index.phtml/itemid/687104>. skin december 2018 volume 2 supplemental issue copyright 2018 the national society for cutaneous medicine 110 rising derm stars topical jak inhibitor ruxolitinib for vitiligo treatment brooke rothstein, md, deep joshipura, md, ami saraiya, md, rana abdat, md, huda ashkar, md, yana turkowski, md, vaneeta sheth, md, victor huang, md, shiu chung au, md, courtney kachuk, rn, nicole dumont, alice b. gottlieb, md, phd, david rosmarin, md background: the often visible, disfiguring lesions of vitiligo may have a major impact on patient quality of life. unfortunately, existing therapies for vitiligo are limited in efficacy and can be associated with undesirable side effects. janus kinase (jak) inhibitors such as ruxolitinib may offer a new and safe therapeutic option for vitiligo treatment by targeting the t-helper 1 (th1) cell immune mediated pathway that defines vitiligo pathogenesis. methods: a 20-week open-label proof-ofconcept trial of twice daily topical application of ruxolitinib 1.5% cream in 12 adult patients with a minimum of 1% affected body surface area (bsa) of vitiligo. topical application was limited to 10% bsa to avoid systemic side effects. the primary outcome was improvement in vitiligo assessment severity index (vasi) from baseline to week 20. results: of the 12 patients screened, 11 patients enrolled and 9 patients completed the study (mean age 51.72, male 54%). a 23% (95% ci: 4% 43%, p=0.02) improvement in overall vasi scoring from baseline to week 20 was observed. an approximately 76% (95% ci: 53% 99%, p=0.001) improvement in facial vasi scoring was observed in four patients with significant facial involvement at baseline (figure 1, figure 2). three patients experienced minimal non-statistically significant repigmentation in vitiligo located on the body and 1 patient had slight acral re-pigmentation (figure 1). adverse events were minor including erythema, hyperpigmentation and transient acne on skin where ruxolitinib was applied. as laboratory monitoring was not performed in our patients after the baseline visit, the authors cannot comment on potential laboratory adverse events, but it was assumed these were not likely to occur with topical application. conclusion: twice daily application of topical ruxolitinib 1.5% cream provided significant facial vitiligo re-pigmentation and may offer a valuable new treatment for vitiligo. after the conclusion of this study, the trial was extended 32 weeks in 8 patients, 4 of whom experienced an additional statistically significant improvement in facial vasi [92% ± 7.1%, (p = .0001)] at 52 weeks. three of 6 patients experienced repigmentation of non-acral upper extremity vitiligo (12.6% ± 19.5%), two of whom underwent simultaneous nbuvb phototherapy and had previously failed phototherapy and topical ruxolitinib 1.5% cream as single agent treatment regimens. a multi-centered phase 2 randomized controlled trial was designed based on the encouraging results of our proof-of-concept study and is currently underway at 26 research sites throughout the country. skin december 2018 volume 2 supplemental issue copyright 2018 the national society for cutaneous medicine 111 figure 1: percent improvement in vasi scoring. figure 2: clinical improvement in facial vitiligo. references: references: 1. rashighi m, agarwal p, richmond jm, et al. cxcl10 is critical for the progression and maintenance of depigmentation in a mouse model of vitiligo. science translational medicine. 2014;6(223). 2. harris je, harris th, weninger w, wherry ej, hunter ca, turka la. a mouse model of vitiligo with focused epidermal depigmentation requires ifn-gamma for autoreactive cd8(+) t-cell accumulation in the skin. the journal of investigative dermatology. 2012;132(7):1869-1876. 3. mosmann tr, coffman rl. th1 and th2 cells: different patterns of lymphokine secretion lead to different functional properties. annual review of immunology. 1989;7:145-173. 4. rothstein b, joshipura d, saraiya a, abdat r, turkowski y, sheth v, huang v, au sc, kachuk c, dumont n, gottlieb ab, rosmarin d. treatment of vitiligo with the topical janus kinase inhibitor ruxolitinib. jaad. 2017 jun:76(6):1054-1060. 5. joshipura d, alomran a, zancanaro p, rosmarin d. treatment of vitiligo with the topical janus kinase inhibitor ruxolitinib: a 32-week open-label extension study with optional narrow-band ultraviolet b. jaad. 2018 jun;78(6):1205-1207. s2010514 fcpanp 2020 silverberg_without qr code.indd presented at the 5th fall clinical dermatology conference for pas & nps (fcpanp). background • atopic dermatitis (ad) is a chronic inflammatory skin disease characterized by intense pruritus1 • patients with ad have an increased risk of anxiety and depression,2,3 which often correlates with ad severity • the hospital anxiety and depression scale (hads) is a tool that is validated for patients with ad and used to identify patients with symptoms of anxiety and depression in non-psychiatric settings4 – hads contains 2 components, the anxiety (hads-a) and depression (hads-d) subscales, which make up the total score • dupilumab is a fully human5,6 monoclonal antibody that blocks the shared receptor component for interleukin (il)-4 and il-13, inhibiting signaling of both il-4 and il-13, which are key drivers of type 2-mediated inflammation in multiple diseases7,8 • in the randomized phase 3 solo 1 and 2 trials in adults with moderate-to-severe ad, 16-week treatment with dupilumab vs placebo significantly improved ad signs, symptoms, and quality of life9 • furthermore, in the randomized phase 3 adol trial in adolescents with uncontrolled, moderate-to-severe ad, 16-week treatment with dupilumab vs placebo significantly improved ad signs, symptoms, and quality of life10 dupilumab improves symptoms of anxiety and depression in adults and adolescents with moderate-to-severe atopic dermatitis: a post hoc analysis of three phase 3 trials (liberty ad solo 1 and 2 and adol) jonathan i. silverberg1, weily soong2, benjamin lockshin3, abhijit gadkari4, zhen chen4, ashish bansal4 1george washington university school of medicine, washington dc, usa; 2alabama allergy & asthma center, birmingham, al, usa; 3georgetown university, rockville, md, usa; 4regeneron pharmaceuticals, inc., tarrytown, ny, usa analysis • efficacy was analyzed in all randomized patients (full analysis set), and safety outcomes were analyzed in patients who received ≥ 1 dose of study drug • continuous endpoints are reported as least squares (ls) means with standard errors (ses) – data were treated as missing after rescue medication use or early discontinuation – missing data were imputed using multiple imputation with analysis of covariance, with treatment group, disease severity, study identifier (solo), and region (solo) or baseline weight (adol) as fixed factors • categorical endpoints were analyzed using a cochran–mantel– haenszel test adjusted by the same fixed factors as continuous endpoints – patients were considered non-responders from the time of rescue medication use or withdrawal • safety was assessed among patients who received ≥ 1 dose of any study drug objective • to evaluate the effect of dupilumab on anxiety and depression in adults and adolescents with moderate-to-severe ad solo 1 (nct02277743) & solo 2 (nct02277769) n = 1,379 safety follow-up through week 28 1:1:1 r placebo dupilumab 300 mg q2w dupilumab 300 mg qw adol (nct03054428) n = 251 safety follow-up through week 28 baseline 1:1:1 r placebo q2w dupilumab 200 or 300 mg q2w dupilumab 300 mg q4w week 16 week 28 figure 1. study designs. q4w, every 4 weeks; r, randomization. 0 10 20 30 40 50 60 70 80 90 100 placebo (n1 = 183) 9.8%p ro p o rt io n o f p a ti e n ts w it h h a d s -a < 8 ( % ) dupilumab 300 mg q2w (n1 = 196) (a) dupilumab 300 mg qw (n1 = 209) *** 40.8% *** 39.2% (b) (c) (d) (e) (f) 0 10 20 30 40 50 60 70 80 90 100 placebo (n1 = 41) 17.1% p ro p o rt io n o f p a ti e n ts w it h h a d s -a < 8 ( % ) dupilumab 200 or 300 mg q2w (n1 = 47) dupilumab 300 mg q4w (n1 = 42) * 36.2% 35.7% 0 10 20 30 40 50 60 70 80 90 100 placebo (n1 = 139) 14.4% p ro p o rt io n o f p a ti e n ts w it h h a d s -d < 8 ( % ) dupilumab 300 mg q2w (n1 = 148) dupilumab 300 mg qw (n1 = 160) *** 50.7% *** 46.3% 0 10 20 30 40 50 60 70 80 90 100 placebo (n1 = 14) 7.1%p ro p o rt io n o f p a ti e n ts w it h h a d s -d < 8 ( % ) dupilumab 200 or 300 mg q2w (n1 = 19) dupilumab 300 mg q4w (n1 = 23) * 42.1% ** 65.2% 0 10 20 30 40 50 60 70 80 90 100 placebo (n1 = 212) 9.0% p ro p o rt io n o f p a ti e n ts w it h h a d s -a a n d h a d s -d < 8 ( % ) dupilumab 300 mg q2w (n1 = 229) dupilumab 300 mg qw (n1 = 238) *** 40.2% *** 39.1% 0 10 20 30 40 50 60 70 80 90 100 placebo (n1 = 42) 16.7% p ro p o rt io n o f p a ti e n ts w it h h a d s -a a n d h a d s -d < 8 ( % ) dupilumab 200 or 300 mg q2w (n1 = 49) dupilumab 300 mg q4w (n1 = 44) * 38.8% * 36.4% figure 3. proportions of patients at week 16 with: hads-a < 8a, (a) solo and (b) adol; hads-d < 8b, (c) solo and (d) adol; and hads-a < 8c and hads-d < 8c, (e) solo and (f) adol. aamong patients with hads-a baseline values ≥ 8. bamong patients with hads-d baseline values ≥ 8. camong patients with baseline values ≥ 8 in ≥ 1 of hads-a or hads-d. * p < 0.05; ** p < 0.01; *** p ≤ 0.0001. n1, number of patients included in analysis. 0 10 20 30 40 50 60 70 80 90 100 placebo (n1 = 108) 15.7% p ro p o rt io n o f p a ti e n ts w it h h a d s -a < 1 1 dupilumab 300 mg q2w (n1 = 97) (a) dupilumab 300 mg qw (n1 = 97) *** 56.7% *** 44.3% (b) 0 10 20 30 40 50 60 70 80 90 100 placebo (n1 = 17) 23.5% p ro p o rt io n o f p a ti e n ts w it h h a d s -a < 1 1 dupilumab 200 or 300 mg q2w (n1 = 24) dupilumab 300 mg q4w (n1 = 25) 37.5% 48.0% (c) 0 10 20 30 40 50 60 70 80 90 100 placebo (n1 = 71) 15.5% p ro p o rt io n o f p a ti e n ts w it h h a d s -d < 1 1 dupilumab 300 mg q2w (n1 = 61) dupilumab 300 mg qw (n1 = 75) *** 62.3% ** 45.3% (d) 0 10 20 30 40 50 60 70 80 90 100 placebo (n1 = 6) 33.3% p ro p o rt io n o f p a ti e n ts w it h h a d s -d < 1 1 dupilumab 200 or 300 mg q2w (n1 = 8) dupilumab 300 mg q4w (n1 = 10) 37.5% 70.0% (e) (f) 0 10 20 30 40 50 60 70 80 90 100 placebo (n1 = 133) 14.3%p ro p o rt io n o f p a ti e n ts w it h h a d s -a a n d h a d s -d < 1 1 dupilumab 300 mg q2w (n1 = 120) dupilumab 300 mg qw (n1 = 123) *** 54.2% *** 42.3% 0 10 20 30 40 50 60 70 80 90 100 placebo (n1 = 17) 23.5% p ro p o rt io n o f p a ti e n ts w it h h a d s -a a n d h a d s -d < 1 1 dupilumab 200 or 300 mg q2w (n1 = 24) dupilumab 300 mg q4w (n1 = 27) 33.3% 48.1% figure 4. proportions of patients at week 16 with: hads-a < 11a, (a) solo and (b) adol; hads-d < 11b, (c) solo and (d) adol; and hads-a < 11c and hads-d < 11c, (e) solo and (f) adol. aamong patients with hads-a baseline values ≥ 11. bamong patients with hads-d baseline values ≥ 11. camong patients with baseline values ≥ 11 in ≥ 1 of hads-a or hads-d. ** p < 0.01; *** p ≤ 0.0001. –10 –9 –8 –7 –6 –5 –4 –3 –2 –1 0 placebo (n = 460) –1.6 l s m e a n c h a n g e f ro m b a s e lin e in h a d s ( ± s e ) dupilumab 300 mg q2w (n = 457) (a) dupilumab 300 mg qw (n = 462) –5.1 *** –5.5 *** –10 –9 –8 –7 –6 –5 –4 –3 –2 –1 0 placebo (n = 85) –2.5 l s m e a n c h a n g e f ro m b a s e lin e in h a d s ( ± s e ) dupilumab 200 or 300 mg q2w (n = 82) (b) dupilumab 300 mg q4w (n = 84) –3.8 –5.2 * –10 –9 –8 –7 –6 –5 –4 –3 –2 –1 0 placebo (n = 460) –1.4 l s m e a n c h a n g e f ro m b a s e lin e in h a d s -a ( ± s e ) dupilumab 300 mg q2w (n = 457) (c) dupilumab 300 mg qw (n = 462) –2.8 *** –3.0 *** –10 –9 –8 –7 –6 –5 –4 –3 –2 –1 0 placebo (n = 85) –1.6 l s m e a n c h a n g e f ro m b a s e lin e in h a d s -a ( ± s e ) dupilumab 200 or 300 mg q2w (n = 82) (d) dupilumab 300 mg q4w (n = 84) –2.3 –2.7 –10 –9 –8 –7 –6 –5 –4 –3 –2 –1 0 placebo (n = 460) –0.5 l s m e a n c h a n g e f ro m b a s e lin in h a d s -d ( ± s e ) dupilumab 300 mg q2w (n = 457) (e) dupilumab 300 mg qw (n = 462) –2.3 *** –2.5 *** –10 –9 –8 –7 –6 –5 –4 –3 –2 –1 0 placebo (n = 85) –0.8 l s m e a n c h a n g e f ro m b a s e lin in h a d s -d ( ± s e ) dupilumab 200 or 300 mg q2w (n = 82) (f) dupilumab 300 mg q4w (n = 84) –1.4 –2.4 ** figure 2. change from baseline to week 16 in: total hads, (a) solo and (b) adol; hads-a, (c) solo and (d) adol; and hads-d, (e) solo and (f) adol. * p < 0.05; ** p < 0.01; *** p ≤ 0.0001. methods study design • detailed descriptions of the study populations and methodologies have been previously published,9,10 and are summarized below and in figure 1 – adol adolescent patients received 200/300 mg dupilumab q2w (patients with body weight < 60 kg received 200 mg of the study drug; patients with body weight ≥ 60 kg received 300 mg), or 300 mg q4w, or placebo table 1. baseline demographics and clinical characteristics. adult patients (solo 1 & 2 pooled) adolescent patients (adol) placebo (n = 460) dupilumab 300 mg q2w (n = 457) dupilumab 300 mg qw (n = 462) placebo (n = 85) dupilumab 200/300 mg q2w (n = 82) dupilumab 300 mg q4w (n = 84) age, mean (sd), years 38.4 (14.03) 38.3 (14.37) 38.2 (14.48) 14.5 (1.78) 14.5 (1.74) 14.4 (1.59) male, n (%) 250 (54.3) 267 (58.4) 281 (60.8) 53 (62.4) 43 (52.4) 52 (61.9) duration of ad, mean (sd), years 28.8 (14.43) 27.9 (15.20) 27.6 (15.38) 12.3 (3.44) 12.5 (2.97) 11.9 (3.18) patients with iga score = 4, n (%) 225 (48.9) 223 (48.8) 218 (47.2) 46 (54.1) 43 (52.4) 46 (54.8) easi score, mean (sd) 34.0 (14.38) 32.4 (13.32) 32.5 (13.34) 35.5 (13.97) 35.3 (13.84) 35.8 (14.82) peak pruritus nrs score, mean (sd) 7.4 (1.81) 7.4 (1.76) 7.3 (1.94) 7.7 (1.62) 7.5 (1.52) 7.5 (1.84) bsa affected by ad, mean (sd), % 55.8 (23.25) 53.7 (22.21) 54.1 (22.29) 56.4 (24.13) 56.0 (21.40) 56.9 (23.51) scorad score, mean (sd) 68.8 (14.45) 67.1 (13.71) 67.5 (13.34) 70.4 (13.25) 70.6 (13.89) 69.8 (14.12) poem score, mean (sd) 20.6 (5.9) 20.3 (6.0) 20.7 (5.9) 21.1 (5.4) 21.0 (5.0) 21.1 (5.5) (c)dlqi total score, mean (sd) 15.1 (7.47) 14.7 (7.25) 15.1 (7.47) 13.1 (6.72) 13.0 (6.21) 14.8 (7.38) hads total score, mean (sd) 13.2 (8.33) 13.0 (7.43) 13.7 (8.15) 11.6 (7.76) 12.6 (8.04) 13.3 (8.17) hads-a score, mean (sd) 7.4 (4.52) 7.3 (4.14) 7.4 (4.18) 7.4 (4.41) 8.1 (4.62) 8.0 (4.87) hads-a ≥ 8, n (%) 183 (39.8) 196 (42.9) 209 (45.2) 41 (48.2) 47 (57.3) 42 (50.0) hads-a ≥ 11, n (%) 108 (23.5) 97 (21.2) 97 (21.0) 17 (20.0) 24 (29.3) 25 (29.8) hads-d score, mean (sd) 5.7 (4.56) 5.7 (4.07) 6.2 (4.67) 4.3 (3.86) 4.4 (4.15) 5.2 (4.17) hads-d ≥ 8, n (%) 139 (30.2) 148 (32.4) 160 (34.6) 14 (16.5) 19 (23.2) 23 (27.4) hads-d ≥ 11, n (%) 71 (15.4) 61 (13.3) 75 (16.2) 6 (7.1) 8 (9.8) 10 (11.9) easi scores reported on scale from 0 to 72, peak pruritus nrs scores reported on scale from 0 to 10, scorad scores reported on scale from 0 to 103, poem scores reported on scale from 0 to 28, (c)dlqi scores reported on scale from 0 to 30, hads scores reported on scale from 0 to 21. bsa, body surface area; (c)dlqi, (children’s) dermatology life quality index; easi, eczema area and severity index; iga, investigator’s global assessment; n, number of patients; nrs, numerical rating scale; poem, patient-oriented eczema measure; scorad, scoring atopic dermatitis; sd, standard deviation. table 2. safety assessment during the treatment period. patients with event, n (%) adult patients (solo 1 & 2 pooled) adolescent patients (adol) placebo (n = 456) dupilumab 300 mg q2w (n = 465) dupilumab 300 mg qw (n = 455) placebo (n = 85) dupilumab 200/300 mg q2w (n = 82) dupilumab 300 mg q4w (n = 83) ≥ 1 teae 313 (68.6) 321 (69.0) 307 (67.5) 59 (69.4) 59 (72.0) 53 (63.9) teae leading to permanent study discontinuation 7 (1.5) 6 (1.3) 7 (1.5) 1 (1.2) 0 0 death 0 0 1 (0.2)a 0 0 0 treatment-emergent sae 24 (5.3) 11 (2.4) 10 (2.2) 1 (1.2) 0 0 teaes occurring in ≥ 5% of patients in any group in any trial (pt) dermatitis atopic 148 (32.5) 62 (13.3) 59 (13.0) 21 (24.7) 15 (18.3) 15 (18.1) nasopharyngitis 39 (8.6) 42 (9.0) 45 (9.9) 4 (4.7) 3 (3.7) 9 (10.8) upper respiratory tract infection 10 (2.2) 13 (2.8) 20 (4.4) 15 (17.6) 10 (12.2) 6 (7.2) headache 24 (5.3) 40 (8.6) 33 (7.3) 9 (10.6) 9 (11.0) 4 (4.8) injection-site reaction 28 (6.1) 51 (11.0) 72 (15.8) 1 (1.2) 0 1 (1.2) conjunctivitisb 10 (2.2) 45 (9.7) 33 (7.3) 4 (4.7) 8 (9.8) 9 (10.8) adeath was unrelated to treatment (for a full description of the events, see simpson, et al. 20169); bincludes the following pts: conjunctivitis, conjunctivitis bacterial, conjunctivitis viral, conjunctivitis allergic, and atopic keratoconjunctivitis. meddra, medical dictionary for regulatory activities; pt, meddra preferred term; sae, serious adverse event; teae, treatment-emergent adverse event. references: 1. weidinger s, novak n. lancet. 2016;387:1109-22. 2. yu sh, silverberg ji. j invest dermatol. 2015;135:3183-6. 3. eckert l, et al. j am acad dermatol. 2017;77:274-9. 4. silverberg ji, et al. j invest dermatol. 2019;139:1388-91. 5. macdonald le, et al. proc natl acad sci u s a. 2014;111:5147-52. 6. murphy aj, et al. proc natl acad sci u s a. 2014;111:5153-8. 7. gandhi na, et al. nat rev drug discov. 2016;15:35-50. 8. gandhi na, et al. expert rev clin immunol. 2017;13:425-37. 9. simpson el, et al. n engl j med. 2016;375:2335-48. 10. simpson el, et al. jama derm. 2019; nov 6 [epub ahead of print]. doi: https://doi.org/10.1001/jamadermatol.2019.3336. acknowledgments: data first presented at the 2020 annual meeting of the american academy of allergy, asthma and immunology (aaaai); philadelphia, pa, usa; march 13–16, 2020. research sponsored by sanofi and regeneron pharmaceuticals, inc. clinicaltrials.gov identifiers: nct02277743 (liberty ad solo 1), nct02277769 (liberty ad solo 2), and nct03054428 (liberty ad adol). medical writing/editorial assistance provided by luke shelton, phd, of excerpta medica, funded by sanofi genzyme and regeneron pharmaceuticals, inc. disclosures: silverberg ji: abbvie, celgene, eli lilly, gsk, incyte, kiniksa pharmaceuticals, leo pharma, realm therapeutics, regeneron pharmaceuticals, inc. – investigator; abbvie, eli lilly, galderma, gsk, incyte, kiniksa pharmaceuticals, leo pharma, medimmune (astrazeneca), menlo therapeutics, pfizer, realm therapeutics, regeneron pharmaceuticals, inc. – consultant; regeneron pharmaceuticals, inc. – speaker. soong w: astrazeneca, regeneron pharmaceuticals, inc. – speaker, advisory board member, investigator; abbvie, regeneron pharmaceuticals, inc. – consultant; abbvie – investigator; aimmune, gsk, leo pharma, novartis, pfizer, teva, vanda pharmaceuticals – investigator grants; genentech – investigator grants, honorarium, advisory board member; stallergenes greer – advisory board member. lockshin b: eli lilly, regeneron pharmaceuticals, inc. – investigator, speaker; anacor, dermira, franklin bioscience, leo pharma – investigator; abbvie – investigator, speaker, consultant. gadkari a, chen z, bansal a: regeneron pharmaceuticals, inc. − employees and shareholders. conclusions • a large proportion of adult and adolescent patients with ad had symptoms of anxiety or depression at baseline, indicative of a high burden of ad • dupilumab monotherapy improved symptoms of anxiety and depression in adult and adolescent patients with ad, and was well tolerated with an acceptable safety profile methods (cont.) results patients • 1,379 adults were randomized in the solo trials, and 251 adolescents were randomized in the adol trial • baseline demographics and characteristics were balanced between the treatment groups in the individual trials (table 1) • adolescents had numerically higher baseline disease severity than adults efficacy assessment safety skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 752 clinical management recommendations the importance of medication adherence in the treatment of actinic keratosis: an expert consensus panel danny zakria, md, mba1, april w. armstrong, md, mph2, brian berman, md3, james q. del rosso, do4, mark lebwohl, md1, todd e. schlesinger, md5, darrell rigel, md, ms1 1 department of dermatology, icahn school of medicine at mount sinai, new york, ny 2 department of dermatology, keck school of medicine, university of southern california, los angeles, ca 3 department of dermatology & cutaneous surgery, university of miami miller school of medicine, miami, fl 4 department of dermatology, touro university, henderson, nv 5 dermatology & laser center of charleston, clinical research center of the carolinas, charleston, south carolina abstract background: actinic keratosis (ak) is one of the most common dermatologic diagnoses. while there are several treatment options, many topical therapies have poor adherence due to duration of treatment and local skin reactions (lsrs). objective: to review the available literature on the most commonly used patientadministered field-directed therapies for ak and create consensus statements on the role of medication adherence in improving ak outcomes. methods: a literature search of pubmed was completed for english-language original research articles reporting efficacy, safety, and tolerability data for 5-fu, diclofenac gel, imiquimod cream, and tirbanibulin. once the articles were selected, they were distributed to a panel consisting of seven dermatologists with extensive expertise in managing aks. each panelist reviewed the articles and assigned them a level of evidence based on strength of recommendation taxonomy (sort) criteria. the panelists then met to review and discuss the studies and created consensus statements on the management of aks and the importance of medication compliance. a modified delphi process was used to approve the adoption of each statement. results: the literature search produced 1,326 articles that met search criteria. after screening these articles for relevance and applying the inclusion criteria, 17 articles were chosen to be reviewed by the panel and assigned a level of evidence based on sort criteria. the panel then created six consensus statements that received a unanimous vote for adoption. conclusion: while there are several options for the treatment of ak, there is little consensus on a standard of care. clearance rates for the most common topical field therapies vary significantly but are also difficult to directly compare due to differences in methodology for measuring and assessing outcomes. overall, it is clear that an efficacious, tolerable, and convenient treatment for aks is critical to optimal adherence and management and, given the results of recent studies, tirbanibulin may be the best topical option for meeting these criteria. skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 753 actinic keratosis (ak) is one of the most common diagnoses in the outpatient setting, with an estimated prevalence of 40 million in the united states (us) in 2004 and a rising incidence.1,2 aks are associated with chronic ultraviolet (uv) damage, and therefore their incidence increases substantially with age.3 in fact, in the us it is the most common dermatologic diagnosis in patients over 45 years of age.4,5 aks can be problematic as they have the potential to develop into a keratinocyte carcinoma (kc), typically a squamous cell carcinoma (scc), the second most common skin cancer in the world.5-8 while scc usually has a high cure rate, a subset of these tumors can metastasize, leading to approximately 4,000 – 9,000 deaths in the us each year.9-13 the risk of transformation into invasive scc is difficult to accurately assess, but some studies cite a risk as high as 16% per lesion-year.14,15 there are two types of treatment methods for aks – lesion-directed therapy and field therapy. lesion-directed therapy targets specific aks that the clinician is able to identify and is commonly used when there are only a few lesions or for patients who may not be compliant with at-home regimens.16 this includes cryosurgery, laser therapy, curettage, and surgery such as an excision or shave biopsy.16 for patients that present to the dermatology office with numerous aks, lesion-directed therapy can be cumbersome and inefficient. additionally, chronic uv exposure can lead to field cancerization, in which areas of cutaneous tissue have a high burden of both clinical and subclinical actinic damage.5 therefore, in order to mitigate the risk of malignant transformation, it is often important to treat the broader area of skin that may include normal appearing tissue with pathologic atypia.5 commonly used fielddirected therapies include 5-fluorouracil (5fu), diclofenac, imiquimod, photodynamic therapy (pdt), and tirbanibulin. while fielddirected therapies are more effective at treating subclinical actinic damage, they can be associated with long regimens and local skin reactions (lsrs) that limit adherence.5,16-18 tirbanibulin is the newest field-directed treatment and was approved by the food and drug administration (fda) for the treatment of aks on the face and scalp at the end of 2020 after two phase 3 clinical trials demonstrated its safety and efficacy.19 one benefit of tirbanibulin is that it has a 5-day course, much shorter than other therapies that require treatment for 2-4 weeks. early data has also shown that tirbanibulin is very tolerable with minimal lsrs. the purpose of this study was for a panel of experts in ak management to review the available literature on the most commonly used patient-administered field-directed therapies for ak and create consensus statements on the role of medication adherence in improving ak outcomes. a literature search of pubmed was completed on january 8, 2023, using the keywords actinic keratosis, actinic keratoses, efficacy, safety, and tolerability, along with the boolean term “and” for english-language original research articles without date restrictions. the articles were required to be original studies, systematic reviews, or metaanalyses reporting efficacy, safety, and tolerability data for 5-fu, diclofenac gel, imiquimod cream, and tirbanibulin. once the articles were selected, they were distributed to a panel consisting of seven dermatologists introduction methods skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 754 with expertise in managing aks. each panelist reviewed the articles and assigned them a level of evidence based on strength of recommendation taxonomy (sort) criteria.20 the panelists then convened on february 16, 2023, to review and discuss the studies and develop consensus statements on the management of aks and the importance of medication compliance. a modified delphi process was used to approve the adoption of each statement.21 this process requires a supermajority vote to adopt a statement or recommendation through multiple rounds of real-time voting. each panel voted a score of 1-9 for adoption. only statements for which at least two-thirds of the panel voted a 7 or higher were adopted. study selection and levels of evidence the initial literature search produced 1,326 articles that met search criteria. after screening these articles for relevance and applying the inclusion criteria, 17 articles were chosen to be reviewed by the panel and assigned a level of evidence. of the 17 selected articles, the panel assigned level 1 evidence to nine articles19,22-29, level 2 evidence to three articles30-32, and level 3 evidence to five articles33-37 as shown in table 1 and 2. consensus statements the panel created seven consensus statements related to ak management. for six of these statements, the panel unanimously voted a level 9 for adoption. there was one statement which was not adopted, as five members of the panel assigned it a level 2 and two members assigned it a level 3 (table 3). statement 1: ak is a common dermatologic disease. ak is one of the most common dermatologic diseases and is the most common dermatologic diagnosis in adults older than 45 years of age.4 its incidence is on the rise, as the number of treated aks per 1,000 medicare patients rose 14.6% between 2007 and 2015.38 it is extremely common outside of the us as well, especially in areas that receive significant uv exposure. in australia, it is estimated that 40% of the population over the age of 40 has at least one ak.39 the world health organization calculated that there were 131,433,084 cases of ak across europe in 2006.40 statement 2: aks can progress to invasive squamous cell carcinoma. the natural history of aks and their ability to transform into invasive scc has been described throughout the literature. one study found that patients with at least 20 aks had an 11-fold greater risk of developing scc and 10-fold greater risk of developing basal cell carcinoma (bcc) compared to those without any.41 not every ak will progress to scc; in fact, spontaneous regression may occur in 15 to 63% of lesions.42 however, even though some aks will regress, they often reappear, and new ones develop in areas of chronically sunexposed skin. one survey study of 1,040 people in australia found 1,873 aks in 59% of the people screened.43 at 12-month followup, although 26% of the lesions were absent in the subgroup with at least one ak, 60% of these participants developed new lesions.43 overall, the total number of aks in the studied population increased by 22% at 12 months.43 while it is difficult to predict which aks will transform into scc and the individual risk of malignant transformation for each lesion, it is clear that aks have the results skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 755 table 1. sort criteria level of evidence for each of the articles pertaining to tirbanibulin. article level of evidence blauvelt a, kempers s, lain e, et al. phase 3 trials of tirbanibulin ointment for actinic keratosis. n engl j med. 2021;384(6):512-520. 1 heppt mv, dykukha i, graziadio s, salido-vallejo r, chapman-rounds m, edwards m. comparative efficacy and safety of tirbanibulin for actinic keratosis of the face and scalp in europe: a systematic review and network meta-analysis of randomized controlled trials. j clin med. 2022;11(6):1654. published 2022 mar 16. 1 rajkumar jr, armstrong aw, kircik lh. individual article: safety and tolerability of topical agents for actinic keratosis: a systematic review of phase 3 clinical trials. j drugs dermatol. 2021;20(10):s4s4s14. 1 kempers s, dubois j, forman s, et al. tirbanibulin ointment 1% as a novel treatment for actinic keratosis: phase 1 and 2 results. j drugs dermatol. 2020;19(11):1093-1100. 2 yavel r, overcash js, cutler d, fang j, zhi j. phase 1 maximal use pharmacokinetic study of tirbanibulin ointment 1% in subjects with actinic keratosis. clin pharmacol drug dev. 2022;11(3):397-405. 2 berman b, grada a, berman dk. profile of tirbanibulin for the treatment of actinic keratosis. j clin aesthet dermatol. 2022;15(10 suppl 1):s3-s10. 3 dao dd, sahni vn, sahni dr, balogh ea, grada a, feldman sr. 1% tirbanibulin ointment for the treatment of actinic keratoses. ann pharmacother. 2022;56(4):494-500. 3 dlott ah, di pasqua aj, spencer sa. tirbanibulin: topical treatment for actinic keratosis. clin drug investig. 2021;41(9):751-755. 3 eisen db, dellavalle rp, frazer-green l, schlesinger te, shive m, wu pa. focused update: guidelines of care for the management of actinic keratosis. j am acad dermatol. 2022;87(2):373-374.e5. 3 skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 756 table 2. sort criteria level of evidence for the articles not pertaining to tirbanibulin. article level of evidence hadley g, derry s, moore ra. imiquimod for actinic keratosis: systematic review and meta-analysis. j invest dermatol. 2006;126(6):1251-1255. 1 pomerantz h, hogan d, eilers d, et al. long-term efficacy of topical fluorouracil cream, 5%, for treating actinic keratosis: a randomized clinical trial. jama dermatol. 2015;151(9):952-960. 1 askew da, mickan sm, soyer hp, wilkinson d. effectiveness of 5fluorouracil treatment for actinic keratosis--a systematic review of randomized controlled trials. int j dermatol. 2009;48(5):453-463. 1 rivers jk, arlette j, shear n, guenther l, carey w, poulin y. topical treatment of actinic keratoses with 3.0% diclofenac in 2.5% hyaluronan gel. br j dermatol. 2002;146(1):94-100. 1 jansen mhe, kessels jphm, nelemans pj, et al. randomized trial of four treatment approaches for actinic keratosis. n engl j med. 2019;380(10):935-946. 1 gupta ak, paquet m. network meta-analysis of the outcome 'participant complete clearance' in nonimmunosuppressed participants of eight interventions for actinic keratosis: a follow-up on a cochrane review. br j dermatol. 2013;169(2):250-259. 1 cunningham tj, tabacchi m, eliane jp, et al. randomized trial of calcipotriol combined with 5-fluorouracil for skin cancer precursor immunotherapy. j clin invest. 2017;127(1):106-116. 2 eisen db, asgari mm, bennett dd, et al. guidelines of care for the management of actinic keratosis. j am acad dermatol. 2021;85(4):e209-e233. 3 skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 757 table 3. consensus statements statement vote statements that were adopted ak is a common dermatologic disease. 7 voted 9 aks can progress to squamous cell carcinoma. 7 voted 9 higher complexity, longer duration, and adverse effects negatively impact adherence to ak treatments. 7 voted 9 lower adherence to ak treatments can lead to lower efficacy. 7 voted 9 prospective, real-world data demonstrate that topical tirbanibulin for ak is effective, well-tolerated, and convenient, based on highly concordant assessments by both patients and clinicians. 7 voted 9 payors and other stakeholders are encouraged to reduce barriers to effective, tolerable, and convenient treatments for aks. 7 voted 9 statements that were not adopted there is an unmet need for effective ak treatments that are of short duration with limited and tolerable adverse effects. 5 voted 2 2 voted 3 skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 758 potential to progress to scc as histopathology reports demonstrate that 60% to 82% of invasive sccs arise from aks.44-46 furthermore, some lesions that are clinically diagnosed as aks may actually be scc or bcc. one study of 220 ak biopsy samples found histopathologic identification of scc in situ (3.2%), invasive scc (1.4%), and bcc (0.5%).47 another study of step sections of 69 lesions originally classified as aks at histopathologic diagnosis were recharacterized as scc in situ (13%), invasive scc (3%), and bcc (4%).48 statement 3: higher complexity, longer duration, and adverse effects negatively impact adherence to ak treatments. it is well documented that adherence to topical medications can be very poor for a variety of dermatologic conditions.49 this may stem from a multitude of factors and several studies have attempted to identify these factors and possible interventions. one systematic review of the associations between dose regimens and medication compliance found that compliance decreased as the number of daily doses increased.50 for ak management specifically, literature reporting adherence and persistence for topical treatments is limited, but one study of 224 ak patients on imiquimod (3.75% and 5%), 5-fu 5%, or 5-fu/salicylic acid (0.5%/10%) in germany, france, and the uk found between 10 and 25% of patients were non-adherent with their prescribed regimen and 23% were non-persistent.51 another study of 305 ak patients that were either currently using a topical ak therapy (diclofenac sodium 3%, imiquimod 5%, 5-fu 5% or 5-fu/salicylic acid (0.5%/10%)) or had done so within the past 12 months found that 88% of patients were either non-adherent, non-persistent, or both with their regimens.52 longer duration and adverse effects certainly play a significant role in adherence to ak treatments. one study of adherence in 20 patients treated with 5-fu 0.5% reported an average adherence rate of 92% in the first week of treatment, but this fell to 82% by the end of treatment at the fourth of week.53 common adverse effects of topical ak therapies such as 5-fu 5% cream, diclofenac 3% gel, and imiquimod 3.75% cream include lsrs such as pain, erythema, burning, stinging, crusting, and flaking.34,54 these adverse effects accompanied with longer regimens between 2 and 16 weeks can require treatment breaks and early cessation.54 in their literature review, lebwohl et. al found that the most important contributors to non-adherence were lengthy treatment duration, severity and persistence of lsrs, and confusion over treatment regimens.54 statement 4: lower adherence to ak treatments can lead to lower efficacy. lower adherence to treatments has an important negative impact as it can lead to decreased efficacy. this, in turn, results in negative health outcomes such as disease worsening and even death.55 the problem is so significant that the world health organization even declared that nonadherence to medications is a “worldwide problem of striking magnitude” in 2003.56 incomplete treatment of aks can increase the risk of malignant transformation to scc, thus leading to increased morbidity and mortality.14 statement 5: prospective, real-world data demonstrate that topical tirbanibulin for ak is effective, well-tolerated, and convenient, based on highly concordant assessments by both patients and clinicians and this suggests that its usage in ak management could lead to improved adherence. skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 759 the patient reported outcomes in actinic keratosis (proak) study is a real-world, single-arm, prospective cohort study for adult patients with aks on the face or scalp who were newly initiated with once daily tirbanibulin.57 a total of 300 patients were enrolled from 32 community practices across the us. ten patients were not included in the 8-week analyses due to missing data, loss to follow-up, or voluntary patient withdrawal of consent. of the remaining 290 patients, 100% of them completed their 5-day oncedaily treatment course. importantly, there were no discontinuations due to adverse drug reactions and there were no serious adverse drug reactions reported at 8 weeks.57 not only was tirbanibulin found to be welltolerated, but it was efficacious as well, with 73.79% of clinicians reporting that their patients aks were completely or partially (at least 75%) cleared based on investigator global assessment (iga) at 8 weeks.58 in clinical practice, many patients become frustrated with lsrs from topical therapies and after just one treatment course they are very reluctant to use them again. however, in the proak study, for 85.17% of tirbanibulintreated patients, their clinicians reported that they are somewhat or very likely to consider tirbanibulin treatment again if the need arises. concordantly, 80.0% of patients noted that they were somewhat or very likely to consider tirbanibulin treatment again if the need arises.57,58 these findings suggest that tirbanibulin usage for ak therapy could lead to enhanced therapeutic adherence. statement 6: payors and other stakeholders are encouraged to reduce barriers to effective, tolerable, and convenient treatments for aks. while efficacy and tolerability are very important factors to ensure medication adoption and treatment success, accessibility is just as important. access to tirbanibulin can be limited, as the cost for a 5-day supply of the ointment can be $1,136 for cash-paying patients or those with inadequate insurance coverage.59 one study that compared costs of various field therapies for ak found the per-regimen cost of tirbanibulin was $990.60 this is less expensive than the most expensive medication studied, 5-fu 0.5% cream ($1,332.08), but far more expensive than the least expensive treatment, 5-fu 5% cream ($384.94).60 when patients face choices between ak therapies with long durations and significant lsrs or high costs, they may be discouraged from seeking care. this can subsequently increase the morbidity, mortality, and overall use of healthcare resources from aks and their associated sccs. in 2013, the estimated cost of treating aks in the us was $1.68 billion.61 early detection and treatment of aks is imperative for both improving outcomes and decreasing costs to the healthcare system, as one veterans affairs study found 3-year savings of $771 per patient treated with 5-fu versus placebo.62 therefore, improving access to effective, tolerable, and convenient treatments such as tirbanibulin should be a priority for payors. while there are multiple options for the treatment of ak, there is little consensus on a standard of care. clearance rates for the most common topical field therapies vary significantly but are also difficult to directly compare due to differences in methodology for measuring and assessing outcomes. after a thorough review of the literature, this panel of dermatologists with significant expertise in managing aks created six consensus statements related to the importance of ak treatment to prevent the development of scc and the role that medication adherence plays conclusion skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 760 in treatment success. study limitations include that not all therapeutic options for ak were considered and the topical field therapies that were included in the review have not all been compared head-to-head. overall, it is evident that an efficacious, tolerable, and convenient treatment for aks is critical to their adequate management and that tirbanibulin may be the best current option to achieve these criteria. conflict of interest disclosures: dz has no relevant conflicts to disclose. awa has served as a consultant and investigator for almirall. bb has served as a consultant and speaker for almirall. jdr is a consultant, research investigator, and speaker for almirall. ml is a consultant for almirall. ts is a consultant and investigator for almirall, galderma and biofrontera. dr has served as a consultant and investigator for almirall. funding: this study was funded in part by an unrestricted educational grant from almirall. corresponding author: danny zakria, md, mba 234 e 85th st. 5th floor new york, ny 10028 phone: (212) 241-6595 email: danny.zakria@mountsinai.org references: 1. bickers dr, lim hw, margolis d, et al. the burden of skin diseases: 2004 a joint project of the american academy of dermatology association and the society for investigative dermatology. j am acad dermatol. 2006;55(3):490-500. doi:10.1016/j.jaad.2006.05.048 2. rigel ds, stein gold lf. the importance of early diagnosis and treatment of actinic keratosis. j am acad dermatol. 2013;68(1 suppl 1):s20-s27. doi:10.1016/j.jaad.2012.10.001 3. siegel ja, korgavkar k, weinstock ma. current perspective on actinic keratosis: a review. br j dermatol. 2017;177(2):350-358. doi:10.1111/bjd.14852 4. landis et, davis sa, taheri a, 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doi:10.1111/j.13654632.2009.04045.x 27. rivers jk, arlette j, shear n, guenther l, carey w, poulin y. topical treatment of actinic keratoses with 3.0% diclofenac in 2.5% hyaluronan gel. br j dermatol. 2002;146(1):94100. doi:10.1046/j.1365-2133.2002.04561.x 28. jansen mhe, kessels jphm, nelemans pj, et al. randomized trial of four treatment approaches for actinic keratosis. n engl j med. 2019;380(10):935-946. doi:10.1056/nejmoa1811850 29. gupta ak, paquet m. network meta-analysis of the outcome 'participant complete clearance' in nonimmunosuppressed participants of eight interventions for actinic keratosis: a follow-up on a cochrane review. br j dermatol. 2013;169(2):250-259. doi:10.1111/bjd.12343 30. kempers s, dubois j, forman s, et al. tirbanibulin ointment 1% as a novel treatment for actinic keratosis: phase 1 and 2 results. j drugs dermatol. 2020;19(11):1093-1100. doi:10.36849/jdd.2020.5576 31. yavel r, overcash js, cutler d, fang j, zhi j. phase 1 maximal use pharmacokinetic study of tirbanibulin ointment 1% in subjects with actinic keratosis. clin pharmacol drug dev. 2022;11(3):397-405. doi:10.1002/cpdd.1041 32. cunningham tj, tabacchi m, eliane jp, et al. randomized trial of calcipotriol combined with 5fluorouracil for skin cancer precursor immunotherapy. j clin invest. 2017;127(1):106116. doi:10.1172/jci89820 33. berman b, grada a, berman dk. profile of tirbanibulin for the treatment of actinic keratosis. j clin aesthet dermatol. 2022;15(10 suppl 1):s3-s10. 34. dao dd, sahni vn, sahni dr, balogh ea, grada a, feldman sr. 1% tirbanibulin ointment for the treatment of actinic keratoses. ann pharmacother. 2022;56(4):494-500. doi:10.1177/10600280211031329 35. dlott ah, di pasqua aj, spencer sa. tirbanibulin: topical treatment for actinic keratosis. clin drug investig. 2021;41(9):751755. doi:10.1007/s40261-021-01068-9 36. eisen db, dellavalle rp, frazer-green l, schlesinger te, shive m, wu pa. focused update: guidelines of care for the management of actinic 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action. world health organization; geneva, switzerland: 2003 57. kircik, l., schlesinger, t., armstrong, a., berman, b., bhatia, n., del rosso, j., lebwohl, m., patel, v., rigel, d., narayanan, s., koscielny, v., & kasujee, i. (2023). impact of actinic keratosis (ak), as measured by patient-reported ak symptoms, and impact on emotions and functioning (using skindex-16) among patients with ak administered tirbanibulin in real-world community practices across the u.s. (proak study). skin the journal of cutaneous medicine, 7(2), s161. https://doi.org/10.25251/skin.7.supp.161 58. schlesinger, t., kircik, l., armstrong, a., berman, b., bhatia, n., del rosso, j., lebwohl, m., patel, v., rigel, d., narayanan, s., koscielny, v., & kasujee, i. (2023). investigator global assessment (iga) of actinic keratosis (ak) among patients administered tirbanibulin in realworld community practices across the u.s., and clinician likelihood to consider tirbanibulin again for future ak treatments (proak study). skin the journal of cutaneous medicine, 7(2), s162. https://doi.org/10.25251/skin.7.supp.162 59. klisyri prices, coupons, copay &amp; patient assistance. drugs.com. (n.d.). retrieved may 3, https://doi.org/10.25251/skin.7.supp.161 https://doi.org/10.25251/skin.7.supp.162 skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 763 2023, from https://www.drugs.com/priceguide/klisyri 60. lampley n 3rd, rigo r, schlesinger t, rossi am. field therapy for actinic keratosis: a structured review of the literature on efficacy, cost, and adherence. dermatol surg. 2023;49(2):124-129. doi:10.1097/dss.0000000000003677 61. lim hw, collins sab, resneck js jr, et al. the burden of skin disease in the united states. j am acad dermatol. 2017;76(5):958-972.e2. doi:10.1016/j.jaad.2016.12.043 62. yoon j, phibbs cs, chow a, weinstock ma; veterans affairs keratinocyte carcinoma chemoprevention trial group. impact of topical fluorouracil cream on costs of treating keratinocyte carcinoma (nonmelanoma skin cancer) and actinic keratosis. j am acad dermatol. 2018;79(3):501-507.e2. doi:10.1016/j.jaad.2018.02.058 https://www.drugs.com/price-guide/klisyri https://www.drugs.com/price-guide/klisyri powerpoint presentation background • significant variability exists within the established guidelines for cutaneous melanoma patient follow-up and surveillance.1 • a validated prognostic 31-gene expression profile (gep) test has been shown to accurately classify a patient’s risk of metastasis within five years post-diagnosis as either low (class 1) or high (class 2).2,3 • the test has been shown to impact management decisions, including frequency of clinical visits, imaging and blood work recommendations, and physician referrals as measured by changes in surveillance practices following receipt of the test result.4-6 methods • a retrospective case review was performed following irb approval at desert surgical oncology, rancho mirage, ca. data were collected from october 2015 through june 2016. • eligible patients had a diagnosis of stage i-iii cutaneous melanoma and underwent gep testing as part of their routine clinical care. • medical records were reviewed by the managing surgical oncologist. a questionnaire was completed for each patient describing the intended management strategy prior to and following the receipt of a gep test result. • recommendations for follow-up were categorized as blood work (labs), imaging, frequency of clinical visits, and referral to medical oncology. • documented management changes were categorized as increased intensity, decreased intensity, or no change, based on comparison of management plans before and after receipt of gep test result. group comparisons were evaluated using fisher’s exact tests. table 4. review of clinical impact studiestable 2. pre-test management plan results table 1. cohort demographics conclusions • the inclusion of gep testing as part of the management strategy at our institution has resulted in significant risk-driven follow-up and surveillance differences between lowand high-risk patients. • results of this study are consistent with previously published reports of the gep’s impact on clinical management. • gep testing in combination with conventional staging methods can be employed to develop a more efficient and individualized follow-up plan based on clinical factors as well as intrinsic biological risk. references 1. cromwell kd, ross mi, xing y, et al. melanoma res 2012;22:376-85. 2. gerami p, cook rw, russell mc, et al. clin cancer res 2015;21:175-83. 3. gerami p, cook rw, wilkinson j, et al. j am acad dermatol 2015;72:780-5 e783. 4. berger ac, davidson rs, poitras jk, et al. curr med res opin 2016;32:1599-604. 5. farberg as, glazer am, white r, rigel ds. j drugs dermatol 2017;16:428-31. 6. schuitevoerder d, heath m, massimino k, et al. ann surg oncol 2017;24:s144. disclosures rwc and fam are employees and stockholders of castle biosciences, inc. the proprietary gep test is clinically available through castle biosciences as the decisiondx®-melanoma test (www.skinmelanoma.com). a retrospective case series to evaluate the clinical utility of a 31-gene expression profile test in cutaneous melanoma patients robert w. cook, phd1, federico a. monzon, md1, david hyams, md2 1castle biosciences, inc., friendswood, tx, 2desert surgical oncology, rancho mirage, ca clinical characteristic overall (n = 70) class 1 (n = 45) class 2 (n = 25) ajcc stage (v7) i 39 (56%) 36 (80%) 3 (12%) ii 29 (41%) 7 (16%) 22 (88%) iii 2 (3%) 2 (4%) 0 (0%) breslow thickness median (range), mm 1.3 (0.4-6.8) 1.0 (0.4-2.5) 2.5 (0.8-6.8) ≤1 mm 25 (36%) 21 (47%) 2 (8%) >1 mm 45 (64%) 24 (53%) 23 (92%) mitotic index <1/mm2 18 (26%) 15 (33%) 3 (12%) ≥1/mm2 52 (74%) 30 (67%) 22 (88%) regression absent 67 (96%) 43 (96%) 24 (96%) present 3 (4%) 2 (4%) 1 (4%) ulceration absent 48 (69%) 39 (87%) 9 (36%) present 22 (31%) 6 (13%) 16 (64%) table 3. changes by class for each surveillance method objective • to determine differences in management strategies and surveillance between class 1 and class 2 patients at a single surgical oncology center. class 1 class 2 decrease increase decrease increase labs 45 0 0 0 imaging* 13 0 0 25 visits 45 0 0 0 referral 1 1 0 5 *p<0.0001, fisher’s exact test figure 1. schematic showing management changes after inclusion of gep test result to existing surveillance plans. gep class was a significant predictor of change in management (p<0.0001, fisher’s exact test). c/a/p: chest, abdomen and pelvis. management modality frequency labs q3 months x 2 years and q6 months x 3 years imaging ct scan q1 year x 5 years or none office visits q3 months x 2 years and q6 months x 3 years referral none study n result berger (2016) prospective, multicenter 163 patients 53% changed management after inclusion of gep result farberg (2017) dermatologist survey 169 physicians 47-50% changed management after inclusion of gep result schuitevoerder (2017) prospective, single center 90 patients 52% of management decision based on gep result using decision tree model current study retrospective, single center 70 patients 100% changed management after inclusion of gep result slide number 1 leo1825b_silverberg4x4-v2 treatment with tralokinumab improves health-related quality of life in adult patients with moderate to severe atopic dermatitis: results from a phase 2b, randomised, double-blind, placebo-controlled study objectives • to evaluate the risk of developing adas with tralokinumab treatment in the phase 2b study. • to investigate reports of anaphylaxis, or other severe hypersensitivity reactions, and compare the incidence of eye disorders, including conjunctivitis, between the placebo and tralokinumab treatment groups. methods study design • patients were randomised 1:1:1:1 to receive subcutaneous tralokinumab (45 mg, 150 mg or 300 mg) or placebo every 2 weeks for 12 weeks on a tcs background (figure 1). • concomitant class 3 (world health organisation) tcs were administered at least once daily during the 2-week run-in and as needed throughout the treatment and follow-up periods. patients • 8) and with ad body surface area involvement of 10%, easi score of 12, scorad of 25 and iga of 3. • key exclusion criteria included: active dermatological conditions that may confound ad diagnosis, allergic or irritant contact dermatitis and history of anaphylaxis following any biologic therapy. measurement of anti-drug antibodies • adas were measured using a validated electrochemiluminescence method (meso scale discovery sector imager 6000). samples for ada response were taken at day 1 (prior to treatment) and weeks 4, 12 and 22. capture of anaphylaxis/serious hypersensitivity reactions • aes associated with anaphylaxis/serious hypersensitivity were captured using the following standardised medical dictionary for regulatory activities queries: hypersensitivity, anaphylactic reaction and anaphylactic/anaphylactoid shock conditions.9 eye disorders • eye disorders, including but not limited to conjunctivitis, were extracted from the aes occurring during treatment for all subjects in each treatment arm: placebo: n=51, tralokinumab 45 mg: n=50, tralokinumab 150 mg: n=51 and tralokinumab 300 mg: n=52. — all events were included regardless of seriousness, causality or any other parameter of the aes. • cases of eye disorders were compared between placebo and tralokinumab arms. statistical analysis • safety data were summarised descriptively according to the highest dosage received by each participant measured in the as-treated population. results patient characteristics • overall, 204 patients were randomised in the phase 2b study and included in the as-treated population: 153 tralokinumab-treated patients and 51 placebo-treated patients. • baseline demographics and disease characteristics were similar between treatment groups.7 anti-drug antibodies • three patients in the tralokinumab 45-mg group had pre-existing adas at baseline. these are likely to be the result of the ‘cut point’ for the ada assay, which is typically set expecting some positive results. • only one tralokinumab-treated patient (300-mg group) had ada formation, which was measured at week 22. the titre was low and had no impact on the observed pharmacokinetics of tralokinumab. — no aes were reported for this patient. • anaphylaxis/severe hypersensitivity reactions • eye disorders • or all eye disorders between the placebo and pooled tralokinumab groups (figure 2). — no dose-related trend was observed, as the greatest frequency of one or more eye disorders was reported for the tralokinumab 150-mg treatment group. • introduction • biologics, including human monoclonal antibodies (mabs), are currently diseases such as psoriasis1 and atopic dermatitis (ad).2 • potential safety concerns regarding the immunogenicity of biologics remain, including development of anti-drug antibodies (adas) and adverse events (aes) such as anaphylaxis and/or severe hypersensitivity reactions.3 • conjunctivitis with treatment, as aes of conjunctivitis were more frequently reported in patients treated with biologics targeting interleukin (il)-13 and il-4.4,5 • tralokinumab is an igg 4 6 and has been evaluated in a phase 2b, randomised, double-blind, placebo-controlled study (nct02347176) in adults with moderate to severe ad. — results of the study showed improvements in the eczema area and severity index (easi), investigator’s global assessment (iga) and scoring atopic dermatitis (scorad) scores with tralokinumab on a background of topical corticosteroids (tcs), with a favourable overall safety and 7 figure 1. study design weeks –6 –2 0 12 22 follow-up period primary endpoint treatment period run-in period screening period tralokinumab 300 mg sc q2w + tcs (n=52) tralokinumab 150 mg sc q2w + tcs (n=51) tralokinumab 45 mg sc q2w + tcs (n=50) patients with moderate to severe ad tcs tcs placebo sc q2w + tcs (n=51) ad, atopic dermatitis; q2w, every 2 weeks; sc, subcutaneous; tcs, topical corticosteroids. 27th eadv congress, 12−16 september 2018, paris, france *eye infection and iridocyclitis were reported by the same patient in the placebo group. †three patients in the tralokinumab 150-mg group reported oedema; and 3) periorbital rash, eye swelling, increased lacrimation and allergic conjunctivitis. ‡staphylococcal eye infection. methods introduction figure 1. study design weeks –6 –2 0 12 22 follow-up period primary endpoint treatment period run-in period screening period tralokinumab 300 mg sc q2w + tcs (n=52) tralokinumab 150 mg sc q2w + tcs (n=51) tralokinumab 45 mg sc q2w + tcs (n=50) patients with moderate to severe ad tcs tcs placebo sc q2w + tcs (n=51) ad, atopic dermatitis; q2w, every 2 weeks; sc, subcutaneous; tcs, topical corticosteroids. fall clinical dermatology conference, october 18-21, 2018, las vegas, nv • atopic dermatitis (ad) is a chronic, in� ammatory skin disease associated with skin barrier disruption and immune-mediated in� ammation characterised by increased levels of type 2 cytokines, including interleukin (il)-13.1,2 • symptoms of ad include intense and debilitating itch, often leading to sleep disruption, anxiety or depression, and reduced health-related quality of life (hrqol).3,4 • the burden of ad may be assessed by dermatology-specific patient-reported outcome measures, including the dermatology life quality index (dlqi). however, it is also important to assess overall aspects of health and mental well-being in patients with ad and to determine how the burden of ad compares with other non-dermatologic health disorders via the use of generic hrqol instruments, such as the 36-item short form health survey version 2 (sf-36v2). —the sf-36v2 is widely used in health research to assess overall hrqol.5,6 • tralokinumab, a fully human igg 4 monoclonal antibody that speci�fically binds to, and neutralizes, il-13,7 showed improvements in eczema area and severity index (easi), investigator’s global assessment (iga), scoring atopic dermatitis (scorad) and dlqi in a phase 2b, randomised, double-blind, placebo-controlled study (nct02347176) in adults with moderate to severe ad.8 • the tralokinumab phase 2b study also included exploratory assessment of improvement in hrqol in patients with moderate to severe ad. objective • to analyse hrqol improvement, as evaluated by the sf-36v2, in patients receiving tralokinumab as treatment for moderate to severe ad in the phase 2b study. methods study design • patients were randomised (1:1:1:1) to tralokinumab (45 mg, 150 mg or 300 mg) or placebo treatment every 2 weeks for 12 weeks on a background of topical corticosteroids (tcs) [figure 1]. • eligible patients were aged 18–75 years with physician-con�firmed diagnosis of ad for >1 year9 and with �10% body surface area involvement, easi score of >12, scorad of >25 and iga score of >3. • key exclusion criteria included: active dermatological conditions that may confound ad diagnosis, allergic or irritant contact dermatitis and history of anaphylaxis following any biologic therapy. • concomitant world health organisation (who) class 3 tcs were administered at least once daily during the 2-week run-in and as needed throughout the treatment and follow-up periods. sf-36v2 • the sf-36v2 includes eight scale scores measuring: bodily pain, general health, mental health, role limitations related to physical health problems, role limitations related to personal or emotional problems, social functioning, vitality and physical functioning, plus physical component summary (pcs) and mental component summary (mcs) scores.5,6 higher scores indicate better health.5,6 • the sf-36v2 was assessed at baseline and at weeks 6, 12 and 22. statistical analyses • sf-36v2 results at each study visit and changes from baseline for each post-baseline visit were reported, with descriptive statistics for each domain and summary score. • all non-missing data for all patients were included in the analysis, up to the point of prohibited ad therapy being received. • mean change from baseline for each domain and summary score was analysed with mixed model with repeated measures, with treatment, visit and treatment-by-visit interaction as categorical factors and baseline sf-36v2 as covariate. nominal p values for each domain and summary score were derived without adjustment for multiple testing. • minimal clinically important difference (mcid) was used to evaluate clinically relevant improvements (adjusted mean difference versus placebo: mcs, 3; pcs, 2; bodily pain, 3; general health, 2; mental health, 3; role-physical, 3; role-emotional, 4; social functioning, 3; vitality, 2; physical functioning, 3). • results are presented for the tralokinumab 300-mg treatment and placebo treatment groups at week 12, as the tralokinumab 300-mg dose was chosen for further evaluation in phase 3 trials. results patient characteristics • overall, 204 patients were randomised in the phase 2b study; of these, 52 patients received tralokinumab 300 mg and 51 patients received placebo. • mean (standard deviation [sd]) age at baseline was 39.4 (14.5) years for placebo and 35.7 (14.6) years for tralokinumab 300 mg; 43.1% (n=22) and 63.5% (n=33) of participants were male in the placebo and tralokinumab 300-mg groups, respectively. • at baseline, mean (sd) easi scores were 26.4 (12.6) and 27.3 (10.9) for the placebo and tralokinumab 300-mg groups, respectively. hrqol • sf-36v2 data were available at baseline for 49 patients in the placebo group and 52 patients in the tralokinumab 300-mg group. • at baseline, mean (sd) mcs was 43.72 (13.23) for the placebo group and 43.02 (12.36) for the tralokinumab 300-mg group; mean (sd) pcs was 47.07 (7.94) and 47.20 (8.17), respectively (table 1). • at week 12, significantly improved sf-36v2 summary scores were seen in patients treated with tralokinumab 300 mg compared to placebo for both mcs (adjusted mean di� erence: 4.23; p=0.011) and pcs (adjusted mean difference: 4.26; p�0.001) [table 1 and figure 2]. • significant improvements were also seen in all other domains for the tralokinumab 300-mg group compared to placebo (i.e. bodily pain, general health, role-physical, role-emotional, social functioning, vitality, physical functioning), except for mental health, which showed a numerical increase but did not reach statistical significance. • mcs and pcs summary scores and all other domains, except for physical functioning, surpassed mcid for the tralokinumab 300-mg group compared to placebo (figure 2) conclusions • treatment with tralokinumab 300 mg on a background of tcs provided significant and clinically relevant improvements over a broad range of hrqol domains in adult patients with moderate to severe ad compared to placebo in this exploratory analysis of a phase 2b study. • moderate to severe ad was associated with a profoundly negative impact on both mental and physical aspects of patients’ lives at baseline. • phase 3 trials using the tralokinumab 300-mg dose are underway to further evaluate and confirm the impact that tralokinumab monotherapy (nct03131648; nct03160885) or tralokinumab in combination with tcs (nct03363854) may have on reducing the disease burden of moderate to severe ad. compared to placebo at week 12 for sf-36v2 domains, with mcid indicated for each score 0 1 2 3 4 5 6 7 8 9 sc o re c o m p ar ed t o p la ce b o mcs pcs bodily pain general health mental health rolephysical roleemotional social functioning vitality physical functioning p=0.011 p 0.001 p=0.001 p=0.014 p=0.079 p=0.002 p=0.007 p=0.003 p=0.013 p=0.031 mcid summary; se, standard error; sf-36v2, 36-item short form health survey version 2. references 1. silverberg ji, kantor r. dermatol clin 2017; 35: 327–334. 2. nutten s. ann nutr metab 2015; 66 (suppl 1): 8–16. 3. eckert l et al. j am acad dermatol 2017; 77: 274–279. 4. drucker am et al. j invest dermatol 2017; 137: 26–30. 5. ware je, jr, sherbourne cd. med care 1992; 30: 473–483. 6. ware je, jr et al. user’s manual for the sf-36v2 health survey. 2nd ed. qualitymetric incorporated; lincoln, ri: 2007. 7. popovic b et al. j mol biol 2017; 429: 208–219. 8. wollenberg a et al. j allergy clin immunol 2018; pii: s0091-6749(18)30850-9. doi: 10.1016/j. jaci.2018.05.029. [epub ahead of print]. 9. acknowledgements the tralokinumab phase 2b study was sponsored by medimmune. this poster was sponsored by leo pharma. medical writing and editorial support was provided by natalie prior and jane beck from complete healthvizion, funded by leo pharma. table 1. summary of sf-36v2 scores at baseline and adjusted mean change in sf-36v2 from baseline at week 12 mcs pcs bodily pain general health mental health rolephysical role emotional social functioning vitality physical functioning placebo sf-36v2 score at baseline, mean (sd) n=49 mean (sd) 43.72 (13.23) 47.07 (7.94) 45.10 (10.41) 42.24 (9.31) 45.11 (11.65) 45.32 (11.79) 43.71 (13.36) 45.30 (11.58) 45.37 (11.06) 50.01 (8.36) adjusted mean change from baseline in sf-36v2 at week 12,* mean (se) n=36 mean (se) 1.18 (1.222) –0.21 (0.907) –0.43 (1.369) 0.00 (1.022) 1.03 (1.297) –0.02 (1.109) 0.20 (1.278) 1.57 (1.271) 1.39 (1.208) 0.66 (0.883) tralokinumab 300 mg sf-36v2 score at baseline, mean (sd) n=52 mean (sd) 43.02 (12.36) 47.20 (8.17) 44.64 (11.55) 42.47 (10.16) 43.98 (11.18) 45.70 (10.81) 44.83 (13.30) 43.99 (11.64) 44.37 (10.71) 50.22 (8.08) adjusted mean change from baseline in sf-36v2 at week 12,* mean (se) n=46 mean (se) 5.41 (1.095) 4.05 (0.828) 5.63 (1.242) 3.43 (0.934) 4.12 (1.164) 4.80 (1.008) 4.95 (1.160) 6.81 (1.138) 5.47 (1.087) 3.26 (0.799) *analysis of sf-36v2 change from baseline with repeated measures, excluding data after prohibited medications. mcs, mental component summary; pcs, physical component summary; sd, standard deviation; se, standard error; sf-36v2, 36-item short form health survey version 2. jonathan i silverberg,1 nana kragh,2 emma guttman-yassky,3 andreas wollenberg4 1departments of dermatology, preventive medicine, and medical social sciences, feinberg school of medicine, northwestern university, chicago, il, usa; leo pharma a /s, ballerup, denmark; department of dermatology and the laboratory for inflammatory skin diseases, icahn school of medicine at mount sinai, new york, ny, usa; department of dermatology and allergy, ludwig maximilian university, munich, germany patient-reported outcomes in subjects with plaque psoriasis treated with tapinarof cream: results from a phase 2b, randomized parallel-group study neal bhatia, md;1 david rubenstein, md, phd;2 anna m. tallman, pharmd3 1therapeutics clinical research, san diego, ca, usa; 2dermavant sciences, inc., durham, nc, usa; 3dermavant sciences, inc., new york, ny, usa synopsis ■ psoriasis is a chronic, immune-mediated disease characterized by scaly, erythematous, and pruritic plaques that can be painful and disfiguring1 ■ the burden of psoriasis is similar to other long-term conditions, such as congestive heart failure and chronic lung disease, and has a profound impact on mental health and wellbeing2 ■ although multiple options are available for the treatment of plaque psoriasis, there is a need for efficacious topical therapies that can be used without body surface area (bsa) restrictions or concerns for the duration of treatment ■ tapinarof is a therapeutic aryl hydrocarbon receptor modulating agent (tama) under investigation for the treatment of psoriasis and atopic dermatitis ■ this phase 2b dose-finding study (clinicaltrials.gov id: nct02564042) was designed to assess the efficacy and safety of tapinarof cream in subjects with plaque psoriasis ■ the primary analysis showed that tapinarof cream was efficacious and well tolerated in adult subjects with psoriasis and may represent an effective option in the topical treatment of the disease1 objectives ■ to present the patient-reported outcomes from the phase 2b study in subjects with psoriasis following treatment with topical tapinarof cream, including subject global impression of overall severity of psoriasis symptoms, overall severity of pruritus symptoms, and impact of symptoms on subject-reported health outcomes as assessed by the psoriasis symptom diary (psd) methods study design ■ in this multicenter (united states, canada, and japan), phase 2b, double-blind, vehicle-controlled randomized study, adult subjects with psoriasis were randomized 1:1:1:1:1:1 to receive tapinarof cream 0.5% or 1% once (qd) or twice daily (bid) or vehicle qd or bid for 12 weeks and followed up for 4 more weeks (figure 1) figure 1. study design tapinarof 1% bid (n=38) tapinarof 1% qd (n=38) tapinarof 0.5% bid (n=38) tapinarof 0.5% qd (n=38) vehicle bid (n=37) vehicle qd (n=38) double-blind treatment (12 weeks) r follow up (4 weeks) offtreatment adult subjects with stable plaque psoriasis for ≥6 months • aged 18–65 years • bsa ≥1%–≤15% • pga ≥2 (n=227) bid, twice daily; bsa, body surface area; pga, physician global assessment; qd, once daily. study outcomes and statistical analysis ■ the primary endpoint was the proportion of subjects with a pga score of clear or almost clear (0 or 1) and ≥2-grade improvement in pga score from baseline to week 123 ■ subject-reported outcomes assessed in this study included subject global impression of change in overall severity of psoriasis symptoms and of pruritus symptoms from baseline to week 12, and change over time in daily psd scores – subjects were asked to rate the overall severity of their psoriasis symptoms and of their pruritus symptoms at baseline on a scale of 1 ‘mild’ to 4 ‘very severe’ – the change in overall severity of psoriasis symptoms and pruritus symptoms from baseline to week 12 was rated by subjects from 1 ‘very improved’ to 7 ‘very worse’ – the psd consisted of the 16 questions in the established version, plus six additional questions to assess the severity and bother of skin flaking, dryness, and bleeding – each question asked about how severe and how bothersome signs and symptoms were to the subject within the last 24-hour period and subjects rated their daily scores from 0 ‘absent’ to 10 ‘worst imaginable’ ■ incidence, frequency, and nature of adverse events (aes) and serious aes were collected from the start of study treatment until end of study visit at week 16 ■ no formal hypothesis tests were planned results subject characteristics ■ a total of 227 subjects (of the 290 subjects originally screened) were randomized into the study at 17 sites in the united states, 12 sites in canada, and 11 sites in japan (intent-to-treat analysis population) ■ of those randomized, 175 subjects (77%) completed the study including the week 16 follow-up visit ■ overall, mean demographic and baseline characteristics were comparable across treatment groups (table 1) ■ most subjects (80%) had a baseline pga category of 3 (moderate) and a baseline mean psoriasis area and severity index (pasi) score of 8.8 (standard deviation 4.5) table 1. baseline subject demographics and characteristics tapinarof 1% cream tapinarof 0.5% cream vehicle bid (n=38) qd (n=38) bid (n=38) qd (n=38) bid (n=37) qd (n=38) mean age, years (sd) 45.9 (11.9) 48.5 (10.6) 49.6 (10.9) 48.7 (9.7) 46.7 (12.6) 46.4 (10.2) male sex, n (%) 26 (68) 26 (68) 24 (63) 25 (66) 23 (62) 29 (76) mean weight, kg (sd) 85.6 (22.5) 86.7 (22.6) 88.6 (27.4) 89.3 (23.1) 87.8 (28.3) 91.6 (21.6) pga score, mean (sd)* 2.9 (0.4) 2.7 (0.5) 3.0 (0.5) 2.9 (0.4) 3.0 (0.3) 2.8 (0.4) pasi score, mean (sd)* 10.6 (5.0) 8.5 (3.6) 8.2 (4.5) 7.9 (4.8) 9.0 (4.3) 8.7 (4.4) % bsa affected, mean (sd)* 8.2 (4.5) 6.5 (3.3) 7.2 (4.5) 6.1 (4.3) 6.6 (3.6) 7.0 (4.6) pruritus score, mean (sd)*† 5.6 (2.6) 4.4 (2.9) 6.2 (2.2) 4.5 (2.6) 5.5 (2.8) 4.9 (2.4) *characteristics provided for the mitt analysis population (n=196); †mean scores based on a scale of 0 ‘absent’ to 10 ‘worst imaginable’. demographics (age, sex and weight) provided for the safety analysis population (n=227). the mitt analysis population included subjects in the itt population minus the subjects from one site due to protocol violation. bid, twice daily; bsa, body surface area; itt, intent-to-treat; mitt, modified intent-to-treat; pasi, psoriasis area and severity index; pga, physician global assessment; qd, once daily; sd, standard deviation. ■ primary endpoint: pga response rates (defined as pga score 0 or 1 and ≥2-grade improvement) at week 12 were higher in the tapinarof cream groups than the vehicle groups (65% [1% bid], 56% [1% qd], 46% [0.5% bid], 36% [0.5% qd] vs 11% [vehicle bid] and 5% [vehicle qd]) and were maintained for 4 weeks after the end of study treatment3 subject impressions ■ at baseline, 88% of subjects rated their psoriasis symptoms as moderate or severe across all treatment groups: 43–61% rated as moderate and 28–44% rated as severe ■ at week 12, a greater proportion of subjects in the tapinarof cream groups (82–88% in the 1% groups and 77–80% in the 0.5% groups) rated the overall severity of their psoriasis symptoms as ‘very/moderately improved’ compared with 35–48% in the vehicle groups (figure 2a) figure 2a. subject impression of change in severity of psoriasis symptoms at week 12 82 88 77 80 48 35 17 12 15 10 37 25 00 4 7 5 20 p ro p o rt io n o f su b je ct s, % 60 70 80 90 100 50 40 30 20 0 10 very/moderately improved minimally improved no change tapinarof 1% bid (n=23) tapinarof 1% qd (n=25) tapinarof 0.5% bid (n=26) tapinarof 0.5% qd (n=29) vehicle bid (n=19) vehicle qd (n=20) results derived from the mitt analysis population including subjects in the itt population minus the subjects from one site due to protocol violation (n=196). n is number of subjects with available results at week 12. hatched portion of bar corresponds to proportion of subjects with ‘moderately improved’ symptoms. bid, twice daily; itt, intent-to-treat; mitt, modified intent-to-treat; qd, once daily. ■ at week 12, a greater proportion of subjects in the tapinarof cream groups (70–76% in the 1% groups and 73–77% in the 0.5% groups) rated the overall severity of their pruritus symptoms as ‘very/moderately improved’ compared with 35–47% in the vehicle groups (figure 2b) figure 2b. subject impression of change in severity of pruritus symptoms at week 12 70 76 77 73 47 35 13 12 13 8 4 7 26 30 12 14 5 20 tapinarof 1% bid (n=23) tapinarof 1% qd (n=25) tapinarof 0.5% bid (n=26) tapinarof 0.5% qd (n=29) vehicle bid (n=19) vehicle qd (n=20) p ro p o rt io n o f su b je ct s, % 60 70 80 90 100 50 40 30 20 0 10 very/moderately improved minimally improved no change results derived from the mitt analysis population including subjects in the itt population minus the subjects from one site due to protocol violation (n=196). n is number of subjects with available results at week 12. hatched portion of bar corresponds to proportion of subjects with ‘moderately improved’ symptoms. bid, twice daily; itt, intent-to-treat; mitt, modified intent-to-treat; qd, once daily. severity of psoriasis symptoms (psd) ■ overall, there was a greater reduction from baseline in mean weekly psd scores in the tapinarof cream groups than the vehicle groups ■ nine psd items (2, 11, 12, 13, 14, 17, 18, 19, and 20 related to itching, scaling, flaking, dryness, and appearance) showed high mean severity scores (≥5) at baseline – by week 12, scores from these items had reduced (improved) more in the tapinarof cream groups compared with the vehicle groups (figure 3) figure 3. mean change from baseline in nine items of the psd at week 12 –4.5 –4.0 –4.2 –4.1 –2.6 –1.9 m e an c h an g e i n p s d s co re 0 –1 –2 –3 –4 –5 tapinarof 1% bid (n=14) tapinarof 1% qd (n=20) tapinarof 0.5% bid (n=21) tapinarof 0.5% qd (n=24) vehicle bid (n=15) vehicle qd (n=18) results derived from the mitt analysis population including subjects in the itt population minus the subjects from one site due to protocol violation (n=196). n is number of subjects with available results at week 12. bid, twice daily; itt, intent-totreat; mitt, modified intent-to-treat; psd, psoriasis symptom diary; qd, once daily. safety ■ overall, 46% (104/227) of subjects had treatment-emergent aes (teaes): 56% in the tapinarof cream groups and 25% in the vehicle groups, and were mostly mild to moderate in severity ■ the most frequently reported teae was folliculitis (table 2) table 2. safety overview and most common teaes (occurring in ≥5% of subjects in any group) preferred term, n (%) tapinarof 1% cream tapinarof 0.5% cream vehicle bid (n=38) qd (n=38) bid (n=38) qd (n=38) bid (n=37) qd (n=38) any teae 26 (68) 20 (53) 22 (58) 17 (45) 9 (24) 10 (26) treatment-related teaes 10 (26) 10 (26) 6 (16) 8 (21) 1 (3) 1 (3) serious teaes 1 (3) 3 (8) 3 (8) 0 0 0 discontinuations due to teaes 5 (13) 5 (13) 4 (11) 1 (3) 0 1 (3) teae by intensity mild 10 (26) 8 (21) 11 (29) 12 (32) 5 (14) 8 (21) moderate 12 (32) 9 (24) 7 (18) 5 (13) 3 (8) 1 (3) severe 4 (11) 3 (8) 4 (11) 0 1 (3) 1 (3) teaes occurring in ≥5% of subjects in any group folliculitis 8 (21) 2 (5) 4 (11) 5 (13) 1 (3) 0 dermatitis contact 4 (11) 4 (11) 1 (3) 3 (8) 0 0 headache 4 (11) 1 (3) 0 1 (3) 1 (3) 1 (3) nasopharyngitis 1 (3) 0 4 (11) 2 (5) 0 2 (5) vomiting 0 0 3 (8) 0 1 (3) 0 acne 2 (5) 0 1 (3) 0 0 0 application-site dermatitis 1 (3)* 2 (5) 0 0 0 0 miliaria 0 2 (5) 0 1 (3) 0 0 dermatitis allergic 2 (5) 0 0 0 0 0 urticaria 0 2 (5) 0 0 0 0 teae was defined as an ae that occurred on or after study treatment start date and on or before the last visit. *all teaes occurred once in each subject except ‘application-site dermatitis’, which occurred twice in a subject from the 1% bid group. ae, adverse event; bid, twice daily; qd, once daily; teae, treatment-emergent adverse event. conclusions ■ in all tapinarof cream groups, a greater proportion of subjects (77–88%) reported psoriasis signs and symptoms as ‘very/moderately improved’ after 12 weeks compared with the vehicle groups (35–48%) ■ similarly, a greater proportion of subjects in the tapinarof cream groups (70–77%) reported the overall severity of pruritus as ‘very/moderately improved’ after 12 weeks compared with the vehicle groups (35–47%) ■ overall, tapinarof cream was well tolerated and these results correspond to the previously reported clinical efficacy findings3 ■ study findings demonstrated that tapinarof cream represents an important potential advance in topical medicine development, with beneficial effects on patient-reported outcomes in patients with psoriasis references 1. menter a et al. j am acad dermatol. 2008;58:829–850; 2. moon hs et al. dermatol ther. 2013;3:117–130; 3. robbins k et al. j am acad dermatol. 2018; doi.org/10.1016/j.jaad.2018.10.037. acknowledgments the authors thank the participating investigators, patients and their families, as well as colleagues involved in the conduct of the study. the authors acknowledge dr. james lee, former employee of dermavant sciences, inc. for his contribution to the abstract. editorial and medical writing support under the guidance of the authors was provided by apothecom, uk and was funded by dermavant sciences, inc. in accordance with good publication practice (gpp3) guidelines (ann intern med. 2015;163:461–464). contact dr. neal bhatia at nbhatia@therapeuticsresearch.com with questions or comments. skin november 2017 volume 1 issue 3 copyright 2017 the national society for cutaneous medicine 177 brief articles basal cell carcinoma with adnexal differentiation, a rare entity and challenging histopathology presentation: a case report lizy mariel paniagua gonzalez md a , ikue shimizu md b a university of texas medical branch, department of internal medicine, galveston, tx b baylor college of medicine, department of dermatology, houston, tx basal cell carcinoma (bcc) is the most common malignant neoplasm in humans. 1 it usually occurs in the fourth decade of life in sun exposed areas, though it can present earlier in immunosuppressed patients. this cancer is a slow growing malignancy with low potential risk for metastasis. [1] basal cell carcinoma has multiple subtypes such as nodular, superficial, morpheaform, micronodular, and others, and can also be divided into indolent and aggressive categories. 2 recent evidence suggests that bcc originate from follicular germinative cells instead of surface epidermal cells as was originally described. 2-4 studies have noted that bcc seems to be derived from the basal stem cells in the follicular bulges, anagen hair bulb, follicular matrix cells, and the interfollicular epidermis. 1,3,4 on occasion, bcc can display unusual variants that show adnexal differentiation. the presence of such adnexal structures makes differentiating between a bcc and a cutaneous adnexal tumor a challenge. although adnexal differentiation does not seem to affect tumor behavior, this diagnostic difficulty can have implications during mohs surgery in terms of calling a frozen section clear of malignancy, as well as overall treatment implications if an aggressive adnexal neoplasm is missed. adnexal bcc is an uncommon histological finding on frozen section pathology during mohs surgery, therefore it is important to abstract we report an 88 year-old male with a history of multiple non-melanoma skin cancers who presented for mohs micrographic surgery with a biopsy proven infiltrative and nodular basal cell carcinoma located on the right posterior ear. during mohs surgery, frozen sections revealed a typical nodular bcc on stage 1. however, on stage 2, frozen section showed nodular aggregates of regular cuboidal cells with pale cytoplasm with areas mimicking multinucleated giant cells. deeper permanent sections were consistent with bcc with adnexal differentiation. this histopathological presentation of basal cell carcinoma is uncommon and we sought to report the clinical and pathological features of this case. introduction skin november 2017 volume 1 issue 3 copyright 2017 the national society for cutaneous medicine 178 recognize this entity to provide the best possible treatment for patients. an 88 year-old male with a history of multiple non-melanoma skin cancers and prostate adenocarcinoma presented for routine dermatological evaluation. on exam, there was a 0.4 cm by 0.3 cm crusted erythematous papule on the back of the right ear. a biopsy was performed showing infiltrative and nodular basal cell carcinoma with erosion and serum crust involving deep borders. for this reason, mohs surgery was recommended. during mohs surgery, the pre-operative size was 1 cm x 0.6 cm. three stages were performed. stage 1 showed focal nodular bcc. (figure 1) stage 2 showed a focus of nodular aggregates of pale cuboidal cells, with some nuclei arranged in a circular fashion, in the reticular dermis. (figure 2a-b) toluidine blue stain revealed a band of lavender colored stroma surrounding the aggregates. (figure 3) a dermatopathologist was consulted since the histology of stage 2 did not resemble the bcc that was noted on stage 1, and there were areas suggestive of multi-nucleated giant cells. the dermatopathologist’s differential diagnosis included histiocyte proliferation, possibly with giant cells, and more specifically an atypical mycobacterial or xanthomatous proliferation. the recommendation was to proceed with mohs surgery to clear the ear, and send the blocks for permanent sections. stage 3 was noted to be clear of both bcc and the pale cells noted on stage 2. permanent section obtained deeper into the block of stage 2 showed nodular aggregates of basaloid cells, some with markedly pale cytoplasm, and a background of prominent eosinophilic stroma consistent with bcc with adnexal differentiation. (figure 4) the post-operative size of the resected lesion was 1.5 x 1.7 cm. the lesion was left to heal via granulation. figure 1: stage 1 of mohs procedure showed focal nodular basal cell carcinoma case report skin november 2017 volume 1 issue 3 copyright 2017 the national society for cutaneous medicine 179 figure 2: stage 2 of mohs surgery showing a focus of nodular aggregates of pale cuboidal cells, with some nuclei arranged in a circular fashion in the reticular dermis figure 3: toluidine blue stain slide revealing a band of lavender colored stroma surrounding the basal cell carcinoma figure 3: clear cells with palisading and prominent basement membranes illustrating basal cell carcinoma with adnexal differentiation from stage 2 this case illustrates a presentation of a basal cell carcinoma with adnexal differentiation. bcc is characteristically described as discrete nests of basaloid cells in the dermis with retraction clefts and peripheral palisading of the cells. 1 the tumor stroma is often pale and mucinous. 1, 5 the basaloid tumor cells are generally pleomorphic and can contain mitotic figures and necrotic areas. [5] certain architectural growth patterns (micronodular, infiltrative) are known to indicate more aggressive biologic behavior, and thus warrant more aggressive treatment. 1 in this case, the bcc had histopathological features that are discussion skin november 2017 volume 1 issue 3 copyright 2017 the national society for cutaneous medicine 180 typically associated with adnexal neoplasms such as clear/pale cells and prominent basement membrane-like stroma surrounding some areas, and a background of prominent eosinophilic stroma. in this case, a possible origin for the tumor would the outer root sheath. bcc with adnexal differentiation can also have structures mimicking follicular structures, apocrine, and sebaceous glands. 2 in 1987, tozawa and akerman described the first basal cell carcinoma with follicular differentiation which they called infundibulocystic basal cell carcinoma. 6 this neoplasm was showed symmetrical, circumscribed aggregates of basaloid cells containing numerous structures resembling infundibular cysts. 6 in addition, other bcc with adnexal differentiations have been described and can be broadly divided into sebaceous, apocrine glands, and follicular lineages. 2 features reminiscent of follicular epithelium include shadow cells and clear cells, while keratinization, sebocytes, tubular structures such as ducts and glands, thickened basement membrane, fibrocyterich collagenous stroma, and signet ring cells can also be seen. 2 names reported in the literature include keratotic bcc, follicular bcc, pleomorphic bcc, bcc with sweat duct differentiation, bcc with sebaceous differentiation, and bcc with clear cells. 1 it is important to distinguish bcc with adnexal differentiation from true adnexal neoplasms, as the biological behavior and treatment may differ. there are multiple adnexal tumors reported. some are benign and others are malignant. benign adnexal tumors include trichoepithelioma, pilomatricoma, sebaceoma, cylindroma, and spiradenoma. some malignant adnexal neoplasms are microcystic adnexal carcinoma, sebaceous carcinoma, and sweat gland carcinoma. 7 there are a variety of different techniques and stains that are useful in distinguishing bcc with adnexal differentiation from true adnexal neoplasms. the classic histopathological features used to distinguish bcc from an adnexal tumor are the peripheral palisading of cells, slit like retraction spaces, and increased mitosis. [7] immunohistochemical stains can be used for any additional types of cells. bcc will stain positive for epithelial cell adhesion molecule (ber-ep4), as will bcc with matricial differentiation, and bcc with sebaceous differentiation. 2 cd 117 (c-kit) expression can be used to identify an adenoid cystic carcinoma instead of a bcc. 8 epithelial membrane antigen (ema) and carcinoembryonic antigen (cea) stains are positive for most adnexal neoplasms except bcc with sweat duct and sebaceous differentiation. 1, 2, 9 tichoepithelioma and bcc can mimic each other, and immunohistochemical stains can be helpful here as well. bcc stroma will be positive for stromelysin 3 and cd 34 negative, with bcl2 positive and ck 15/ck20 negative cells. in contrast, trichoepithelioma would be stromelysin 3 negative, cd 34 positive in the stroma, and with bcl-2, ck 15 and ck20 positive cells. 2,7,8 when it comes to frozen sections during mohs surgery, immunohistochemical stains are not easily available. thus, it is important to be able to recognize and differentiate a variety of bcc with adnexal differentiation and true adnexal tumors. in most cases, cutting deeper into a mohs block may reveal more classic bcc alongside more indeterminate areas, allowing one to make a definitive diagnosis if necessary. a closer examination of stage 1 in this case showed some areas with pale cuboidal cells that were slightly more similar to the cells noted on stage 2 than classic bcc. (figure 3) cutting deeper into the block for stage 2 for skin november 2017 volume 1 issue 3 copyright 2017 the national society for cutaneous medicine 181 frozen sections would also have likely revealed the areas of more classic bcc adjacent to paler, more indeterminate areas. this case is unique, however, in its arrangement of pale cells such that the nuclei were ringed in a fashion resembling multi-nucleated giant cells. basal cell carcinoma with adnexal differentiation is an uncommon histopathological presentation. it is important to remember that bcc can have different histopathological features and variants so that appropriate treatment can be performed. the overall morphological appearance, the histology and a variety of different stains and immunohistochemistry are crucial in discerning bcc from adnexal tumors. when only frozen sections without immunohistochemistry are available, obtaining deeper sections and searching from more classically differentiated areas can aid in making the final diagnosis and planning treatment. conflict of interest disclosures: none. funding: none. corresponding author: lizy mariel paniagua department of internal medicine university of texas medical branch galveston, tx 77555 713-614-71769 lmpaniag@utmb.edu references: 1. crowson, a.n. basal cell carcinoma: biology, morphology, and clinical implications. modern pathology 2006; 19: s127-147 2. chu, s.w, biswas, a. basal cell carcinomas showing histological features generally associated with cutaneous adnexal neoplasm. j cutan pathol 2015;42:1049-1062 3. peterson, s.c., eberl, m., vagnozzi, a.n., belkadi, a., et. al. basal cell carcinoma preferentially arises from stem cells with hair follicle and mechanosensory niches. cell stem cell 2015; 16(4):400-412. 4. kruger, k., blume-peytavi, u., orfanos, c.e. basal cell carcinoma possibly originates from the outer root sheath and/or he bulge region of the vellus hair follicle. arch dermatol res 1999; 291:253-259 5. schirren, c.g., rutten, a., kaudewitz, p., diaz, c., mcclain, s., burgdorf, w.h.c. trichoblastoma and basal cell carcinoma are neoplasms with follicular differentiation sharing the same profile of cytokeratin intermediate filaments. am j of dermatopathol 1997; 19(4):341-350. 6. onishi, m., takahashi, k., maeda, f., akasaka, t. a case of basal cell carcinoma with outer hair follicle sheath differentiation. case rep dermatol 2015;7:352-357. 7. alsaad, k.o., obaidat, n.a., ghazarian, d. skin adnexal neoplasms part 1: an approach to tumors of pilosebaceous unit. j clin path 2007; 60:129-144. 8. obaidat, n.a., alsaad, k.o., ghazarian, d. skin adnexal neoplasms part 2: an approach to tumors of cutaneous sweat glands. j clin pathol 2007; 60:145-159 9. crowson, a.n., magro, c.m., mihm, m.c. malignant adnexal neoplasm. modern pathol 2006; 19: s93-s126. skin may 2019 volume 3 issue 3 copyright 2018 the national society for cutaneous medicine 229 compelling comments passion to heal – dermatology volunteering in the maasai mara, kenya maulik m dhandha, md1 1mdfmr dermatology, augusta, me access to dermatology is still limited in several parts of the world. in august 2018, i was part of a volunteer team of dermatologists, physician assistants and medical assistants in the maasai mara region of kenya. we worked along with the local staff at baraka hospital. our goal was to help evaluate, and triage patients with skin conditions over the period of one week and in the process help educate the local team to continue follow up of those patients. the key highlights of the trip were its well organized nature from ticketing to lodging to itinerary, the supportive local staff, and how grateful patients were with evaluation of their conditions. the key challenges to our work there were limited resources and time available, socio-economic difficulties of the local population, lack of an established dermato-pathology center, etc. management of dermatology patients involved making clinical diagnoses without histopathology and empiric treatment from an available medication formulary. dermatology is a visual field, and it was one of the opportunities to implement our observational skills. the spectrum of medical illnesses was completely different from those seen in the united states. we had to switch from cutaneous oncology to inflammatory skin disorders and infectious disease. herein i describe three interesting cases seen by the group. a middle-aged african male presented with 5-year history of unilateral lower extremity swelling. patient reported no prior trauma or injury to the extremity. on examination, he had significant left lower extremity swelling, overlying hypertrophic/verrucous stasis changes and classic “hanging groin”. prior treatments included leg elevation exercises and various “dressings” with no improvement. given the presentation of unilateral lower extremity swelling and hanging groin, a clinical diagnosis of wuchererria bancroffti induced elephantiasis was made.[1,2] treatment with ivermectin alone only kills microfilariae, but not the adult worm.[3] use of albendazole in combination can aid in treating the adult worm. [3] patient was thus treated with combination of both with instructions to follow up at least yearly for additional treatment as often times adult worm survives the treatment and new microfilariae can occur.[3,4] repeat treatment yearly allows killing newer microfilariae until the adult worm dies of senescence.[1,2] a second interesting case was of onchocerciasis. a middle-aged african female presented with depigmented plaques on the extremities, and itchy nodules and plaques on the thighs (figure 1). on further examination, patient also reported blindness in one eye. clinical diagnosis was consistent with onchocerciasis. the patient was treated skin may 2019 volume 3 issue 3 copyright 2018 the national society for cutaneous medicine 230 figure 1: an african female with depigmented plaques and itchy nodules on the lower extremities. with ivermectin.[4] since it only helps treating the microfilariae, she was asked to follow up in 3 months for repeat treatment. an additional treatment option that is now available, although not the standard of care or goal of local public health programs is treatment with doxycycline 100 mg daily for 6 weeks. it allows killing the adult parasite by depleting its essential endosymbiont (wolbachia) bacterium.[5] another interesting case seen by our team was discoid lupus with possible features of systemic lupus. patient presented to the clinic with history of “lighter skin spots” for several years. he reported “sun sensitivity” and frequent headaches. he had a remote history of oral ulcers. he never had prior biopsy or work up. ideally, ana along with autoimmune work up as well as skin biopsies would help confirm the diagnosis, but could not be done as patient deferred due to socioeconomic reasons. he was started on plaquenil after getting blood counts and hepatic panel. in addition, other teams also saw cases like chromoblastomycosis (based on prior histology from tertiary care center in kenya), possible pityriasis rotunda, and an undiagnosed epidermolysis bullosa. the latter two could not be confirmed due to unavailability of histopathology services and/or genetic testing. the pityriasis rotunda patient was treated with topical corticosteroids with instructions to monitor for any weight loss for potential malignancy. as medical professionals in united states, we often struggle to find optimal plans between ideal treatment and actual available treatment due to insurance and other socioeconomic issues. this “gap” of ideal versus available treatment was even more pronounced in kenya. it was important to recognize the need in the community, limited available resources, and choose the appropriate treatment for patients that was both helpful as well as sustainable in cases of chronic diseases. the practice style was also very different. there were no scheduled appointments. the hospital ran on a different model of walk-in outpatient/acute care clinics. every weekday morning, patients would start lining up outside the triage room and wait in the hospital courtyard. we saw patients with mainly skin conditions, but also occasionally saw patients with other concerns. on average we saw 80-100 patients divided amongst 5-6 teams. (figure 2) the majority of the patients did not speak english and so every team had a translator which happened to be local care provider. this was really helpful in quickly adapting to the available resources in the clinic. in addition, we went to skin may 2019 volume 3 issue 3 copyright 2018 the national society for cutaneous medicine 231 figure 2: the author’s medical team. local schools for deworming treatment of students and for screening them for skin infections. we screened over 500 pediatric patients during these school trips. on the last day at the hospital, they provided us educational time where we were able to discuss interesting cases seen over the week and educate the local providers about common skin conditions. our trip was completely organized by me to we. this allowed physicians, nurse practitioners and medical assistants to focus on medical work alone. the organization’s amazing efforts made sure that the trip was well planned from start to finish including booking of tickets, local transportation in kenya, boarding and lodging, volunteering hours and facility, translators for the clinic, and the beautiful cultural experience around it. the cultural experience allowed us to better understand the local dynamics including patient expectations, resources and strengths of the local staff. although a short trip, it was an opportunity that allowed all of us to not only help patients with skin conditions but also to learn more about the local culture, socio-economic structure and medical practice in maasai mara, kenya. conflict of interest disclosures: none. funding: none. corresponding author: maulik m dhandha, md mdfmr dermatology augusta, me maulikdhandha@gmail.com references: 1. alto w, parasitic diseases, in little black book of international medicine. 2008: burlington, ma 2. va hees c, naafs b, common skin diseases in africa. an illustrated guide. 2001: jan sterken of studio oss 3. gyapong jo, kumaraswami v, biswas g, and ottesen ea, treatment strategies underpinning the global programme to eliminate lymphatic filariasis. expert opin pharmacother 2005; 6: 179-200 4. ottesen e. filariasis, in infectious diseases, jonathan c, steven o, powderly w. 3rd edition. 2010: mosby 5. hoerauf a, new strategies to combat filariasis. expert rev anti infect ther 2006; 4: 211-222 mailto:maulikdhandha@gmail.com synopsis • basal cell carcinoma (bcc) is the most common type of skin cancer1 and ultraviolet exposure is a major risk factor.2 • surgery is a curative option for most patients, but systemic therapy is indicated for a small percentage of patients who develop advanced bcc.3 • vismodegib is a hedgehog signalling pathway inhibitor (hhis) that is approved for treatment of patients with metastatic bcc (mbcc) or locally advanced bcc (labcc) who are not candidates for curative surgery or curative radiotherapy. sonidegib is another hhi that is approved for the treatment of labcc only. • there are no available data for patients who progress on or are intolerant to hhis. • cemiplimab is a fully human antibody, derived using velocimmune technology,4–5 which is a high-affinity, highly potent, hinge-stabilized, immunoglobulin g4 monoclonal antibody directed against programmed cell death-1 (pd-1).6 • cemiplimab has recently been shown to have profound clinical activity as monotherapy in first-line non-small cell lung cancer with ≥50% pd-ligand 1 expression.7 • cemiplimab is approved for treatment of patients with metastatic cutaneous squamous cell carcinoma (cscc) or locally advanced cscc who are not candidates for curative surgery or curative radiation.8 • in a pivotal phase 2 study of patients with advanced bcc who discontinued hhi therapy due to disease progression, intolerance, or no better than stable disease after 9 months, cemiplimab became the first systemic therapy to show clinical benefit in patients with labcc after hhi therapy, with estimated duration of response (dor) exceeding 1 year in 85% of responders.9 cemiplimab produced an objective response rate (orr) of 31% in patients with labcc after treatment with hhi therapy; the safety profile was acceptable and consistent with that previously reported for cemiplimab in other tumor types.9 • here, we present the prespecified interim analysis of the mbcc cohort from the pivotal phase 2 study (nct03132636). objectives • the primary objective is orr by independent central review (icr). • secondary objectives include orr according to investigator review; duration of progression-free survival (pfs) by central and investigator review; overall survival (os); complete response rate by central review; and safety and tolerability of cemiplimab. • interim analysis included patients with the opportunity to be followed for approximately 57 weeks to provide an orr with 95% confidence interval (ci). methods • this is a phase 2, non-randomized, multi-center study of cemiplimab in patients with either mbcc or labcc (figure 1). †or by composite response criteria for patient with both visceral and skin lesions. iv, intravenously; q3w, every 3 weeks; q9w, every 9 weeks; q12w, every 12 weeks; recist 1.1, response evaluation criteria in solid tumors version 1.1; who, world health organization. figure 1. study design group 1 adult patients with metastatic (nodal and distant) bcc group 2 adult patients with labcc cemiplimab 350 mg iv q3w for up to 93 weeks (or until disease progression, unacceptable toxicity, or withdrawal of consent) tumor assessments 1–5 q9w, 6–9 q12w tumor response assessment by icr (recist 1.1 for visceral lesions or modified who criteria for skin lesions)† references 1. puig s et al. clin transl oncol. 2015;17:497–503. 2. wu s et al. am j epidemiol. 2013;178:890–897. 3. migden mr et al. cancer treat rev. 2018;64:1–10. 4. murphy aj et al. proc natl acad sci usa. 2014;111:5153–5158. 5. macdonald le et al. proc natl acad sci usa. 2014;111:5147–5152. 6. burova e et al. mol cancer ther. 2017;16:861–870. 7. sezer a et al. poster presented at european society of medical oncology (esmo) virtual congress 2020. september 19–21, 2020: lba52. 8. migden mr et al. n engl j med. 2018;379:341–351. 9. stratigos a et al. poster presented at esmo virtual congress 2020. september 19–21, 2020: lba47. summary and conclusions • this interim analysis demonstrates that cemiplimab is the first agent to provide clinically meaningful anti-tumor activity, including durable responses, in patients with mbcc after progression or intolerance on hhi therapy. • the safety profile of cemiplimab is consistent with previous reports of cemiplimab in other tumor types. • combined with data from the labcc cohort,9 these results confirm that cemiplimab has substantial activity in advanced bcc tumors. table 4. treatment-emergent adverse events regardless of attribution† mbcc (n=28) n (%) any grade grade ≥3 any teae 26 (92.9) 12 (42.9) serious teaes 8 (28.6) 8 (28.6) teaes leading to treatment discontinuation‡ 1 (3.6) 0 sponsor-identified iraes 8 (28.6) 1 (3.6) teaes associated with an outcome of death‡ 1 (3.6) 1 (3.6) any teae occurring in ≥10% patients or grade ≥3 in ≥5% patients§ fatigue 14 (50.0) 0 diarrhea 10 (35.7) 0 constipation 7 (25.0) 0 pruritus 7 (25.0) 0 pyrexia 6 (21.4) 1 (3.6) arthralgia 5 (17.9) 0 decreased appetite 4 (14.3) 1 (3.6) dizziness 4 (14.3) 0 eczema 4 (14.3) 0 headache 4 (14.3) 1 (3.6) nausea 4 (14.3) 0 weight decreased 4 (14.3) 0 asthenia 3 (10.7) 1 (3.6) blood creatinine increased 3 (10.7) 0 dry mouth 3 (10.7) 0 fall 3 (10.7) 1 (3.6) hematuria 3 (10.7) 0 hyperglycemia 3 (10.7) 1 (3.6) hypertension 3 (10.7) 2 (7.1) hypokalemia 3 (10.7) 1 (3.6) myalgia 3 (10.7) 0 pneumonitis 3 (10.7) 1 (3.6) rash 3 (10.7) 0 vomiting 3 (10.7) 0 weight increased 3 (10.7) 0 †adverse events were coded according to the preferred terms of the medical dictionary for regulatory activities, version 22.1. the severity of adverse events was graded according to the national cancer institute common terminology criteria for adverse events, version 4.03. ‡adverse events leading to death: staphylococcal pneumonia deemed unrelated to treatment. §the events are listed in descending order of frequency in any grade. acknowledgments the authors would like to thank the patients, their families, all other investigators, and all investigational site members involved in this study. the study was funded by regeneron pharmaceuticals, inc. and sanofi. medical writing support and typesetting was provided by kate carolan, phd, of prime, knutsford, uk, funded by regeneron pharmaceuticals, inc. and sanofi. disclosures dr lewis reports personal fees from regeneron pharmaceuticals, inc., and grants, and/or personal fees from array biopharma, merck, roche, incyte, nektar, iovance biotherapeutics, and bristol-myers squibb. dr peris reports advisory board roles with abbvie, leo pharma, janssen, almirall, lilly, galderma, novartis, pierre fabre, and sanofi. dr sekulic reports advisory role with regeneron pharmaceuticals, inc. and roche. dr stratigos reports advisory board or steering committee roles with janssen cilag, regeneron pharmaceuticals, inc., and sanofi, and research support from abbvie, bristol-myers squibb, genesis pharma, and novartis. dr dunn reports research funding from eisai, regeneron pharmaceuticals, inc., and cue biopharma, and advisory board payments from regeneron pharmaceuticals, inc., cue biopharma, and merck. dr eroglu reports advisory roles with array biopharma, regeneron pharmaceuticals, inc., novartis, genetech, and sunpharma, and has received research funding from novartis. dr chang reports advisory roles with regeneron pharmaceuticals, inc. and merck, and research funding from regeneron pharmaceuticals, inc., merck, novartis, and galderma. dr migden reports advisory roles with and travel fees from regeneron pharmaceuticals, inc. and sun pharmaceuticals, advisory role with rakuten medical, and research funding from regeneron pharmaceuticals, inc. and pelle pharm. drs li, yoo, mohan, coates, okoye, seebach, lowy, bowler, and fury are shareholders and employees of regeneron pharmaceuticals, inc. drs baurain and bechter have nothing to disclose. dr hauschild reports institutional funding and personal fees from amgen, bristol-myers squibb, merckserono, msd/merck, philogen, pierre fabre, provectus, regeneron pharmaceuticals, inc., roche, sanofi-genzyme, and novartis, and consultancy fees from oncosec and sun pharma. dr butler reports advisory roles with sanofi-genzyme, novartis, sun pharmaceuticals, pfizer, merck, immunocore, turnstone, bristol-myers squibb, and research funding from merck and takara bio. dr hernandez-aya reports an advisory role with massive bio, personal fees from regeneron pharmaceuticals, inc., sanofi, and bristol-myers squibb, and research funding from immunocore, merck sharp & dohme, polynoma, corvus pharmaceuticals, roche, merck serono, amgen, medimmune, and takeda. dr licitra reports funding (for institution) for clinical studies and research from astrazeneca, boehringer ingelheim, eisai, merck serono, msd, novartis, and roche, has received compensation for service as a consultant/advisor and/or for lectures from astrazeneca, bayer, bristol-myers squibb, boehringer ingelheim, debiopharm, eisai, merck serono, msd, novartis, roche, and sobi, and has received travel coverage for medical meetings from bayer, bristol-myers squibb, debiopharm, merck serono, msd, and sobi. dr neves reports an advisory role with novartis, sanofi-genzyme, castle biosciences and roche, and research funding from castle biosciences and regeneron pharmaceuticals, inc. dr ruiz reports an advisory role with pellepharm, inc. table 2. patient demographics and baseline characteristics characteristics mbcc (n=28) median age, years (range) 65.5 (38–90) ≥65 years, n (%) 15 (53.6) male, n (%) 23 (82.1) ecog ps status, n (%) 0 16 (57.1) 1 12 (42.9) number of patients with prior hhi therapy, n (%) vismodegib 28 (100) sonidegib 3 (10.7) vismodegib + sonidegib 3 (10.7) reason for discontinuation of prior hhi, n (%)† progression of disease on hhi 21 (75.0) intolerant to prior hhi therapy 10 (35.7) intolerant to vismodegib 11 (39.3) intolerant to sonidegib 2 (7.1) no better than stable disease after 9 months on hhi therapy 5 (17.9) primary tumor site, n (%) head and neck 11 (39.3) trunk 14 (50.0) extremity 2 (7.1) anogenital 1 (3.6) metastatic status, n (%) distant only 9 (32.1) distant and nodal 15 (53.6) nodal only 4 (14.3) median duration of exposure, weeks (range) 38.9 (3.0–93.4) median number of doses administered (range) 13 (1–30) †sum is >28 because some patients had more than one reason for discontinuation. table 1. inclusion and exclusion criteria inclusion criteria exclusion criteria • aged ≥18 years • patients with histologically confirmed diagnosis of bcc with at least one measurable lesion ≥10 mm in maximal diameter according to recist 1.1 criteria • patients with metastatic disease that does not meet target lesion criteria per recist 1.1, but have externally visible bcc with bi-dimensional measurements that must both be ≥10 mm • eastern cooperative oncology group performance status (ecog ps) ≤1 • must have been deemed unlikely to benefit from further therapy with a hhi due to any of the following: – prior progression of disease on hhi therapy – intolerance to prior hhi therapy – no better than stable disease after 9 months on hhi therapy • patients were excluded if they had ongoing or recent (within 5 years) evidence of significant autoimmune disease requiring treatment with systemic immunosuppressive treatments • prior treatment with an anti–pd-1/pd-ligand 1 therapy • untreated brain metastases • immunosuppressive corticosteroid doses within 4 weeks prior to the start of cemiplimab • after a screening period of up to 28 days, patients received cemiplimab 350 mg iv q3w; therapy consisted of five 9-week treatment cycles followed by four 12-week treatment cycles (figure 1). • inclusion and exclusion criteria are provided in table 1. • an independent composite review committee reviewed digital medical photography, radiology, and pathology reports from on-treatment biopsies (if any) to adjudicate response status for each tumor assessment. • for patients followed by recist 1.1-only criteria, an independent radiology review committee reviewed the radiology for each tumor assessment. • the data cut-off date for the results reported here was february 17, 2020. results patients • as of data cut-off, 28 patients with mbcc had sufficient follow-up to be considered evaluable for clinical activity; 82.1% were males and median age was 65.5 years (range 38−90) (table 2). table 3. tumor response and duration of response per independent central review n (%), unless otherwise stated mbcc (n=28) best overall response objective response rate, % (95% ci) 21.4 (8.3–41.0)† complete response 0 partial response 6 (21.4) stable disease 10 (35.7) non-complete response/non-progressive disease 3 (10.7) progressive disease 7 (25.0) not evaluable‡ 2 (7.1) disease control rate, % (95% ci)§ 67.9 (47.6–84.1) durable disease control rate, % (95% ci)¶ 46.4 (27.5–66.1) median (range) time to response, months# 3.2 (2.1–10.5) kaplan–meier estimation of duration of response, median (95% ci), months# not reached (9.0−ne) 6 months 100 (ne) 12 months 66.7 (19.5−90.4) probability of progression-free survival, % (95% ci) 6 months 58.1 (37.1−74.3) 12 months 49.8 (29.5−67.1) †orr per investigator was 28.6% (95% ci, 13.2–48.7). ‡of the two patients who were not evaluable, one patient had no post-baseline assessment and one patient had no target or non-target lesions. §defined as the proportion of patients with complete response, partial response, stable disease, or non-partial response/ non-progressive disease at the first evaluable tumor assessment, scheduled to occur at week 9 (defined as 56 days to account for visit windows in the protocol). ¶defined as the proportion of patients with complete response, partial response, stable disease, or non-partial response/ non-progressive disease for at least 27 weeks without progressive disease (defined as 182 days to account for visit windows in the protocol). #data shown are for patients with response. ne, not evaluable. figure 2. time to and duration of response in responding patients by independent central review each horizontal bar represents one patient. patients with confirmed complete response after a minimum of 48 weeks of treatment may elect to discontinue treatment and continue with all relevant study assessments. p a ti e n ts w it h r e s p o n s e ( n = 6 ) month mbcc patients 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 partial response stable disease progressive disease ongoing treatment on study clinical activity • orr per icr was 21.4% (95% ci, 8.3–41.0), with six patients showing a partial response. • orr per investigator assessment was 28.6% (95% ci, 13.2–48.7) (table 3, figure 2). • the disease control rate was 67.9% (95% ci, 47.6–84.1). • the durable disease control rate was 46.4% (95% ci, 27.5–66.1). • among responders, median time to response per icr was 3.2 months (range, 2.1−10.5). observed dor was 9−23 months. all six responses were ongoing at 1 year of treatment, and all six had observed duration of at least 8 months. • median dor had not been reached. • median kaplan–meier estimation of os was 25.7 months (95% ci, 19.5–ne) (figure 3). figure 3. kaplan–meier curve for overall survival by independent central review median os was 25.7 months (95% ci, 19.5–ne). 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 p ro b a b ili ty o f o s month 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 28group 1: mbcc number of patients at risk 27 26 25 24 24 23 18 14 13 9 6 3 1 0 0 figure 4. kaplan–meier curve for progression-free survival by independent central review median pfs was 8.3 months (95% ci, 3.6–19.5). patients with confirmed complete response after a minimum of 48 weeks of treatment may elect to discontinue treatment and continue with all relevant study assessments. p ro b a b ili ty o f p f s 28group 1: mbcc number of patients at risk 26 18 14 14 12 11 7 6 5 3 1 1 0 0 0 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 month 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 safety • treatment-emergent adverse events (teaes) of any grade occurred in 26 (92.9%) patients. the most common teaes regardless of attribution were fatigue (50.0%), diarrhea (35.7%), pruritus (25.0%), and constipation (25.0%) (table 4). • grade ≥3 teaes were observed in 12 (42.9%) patients. hypertension (n=2) was the only grade ≥3 teae regardless of attribution occurring in ≥2 patients. • teaes leading to death occurred in one (3.6%) patient who died from staphylococcal pneumonia, considered unrelated to study treatment. • treatment-related adverse events (traes) of any grade occurred in 22 (78.6%) patients. the most common traes regardless of attribution were fatigue (42.9%), pruritus (25.0%), and arthralgia (17.9%). • grade ≥3 traes were observed in five (17.9%) patients. • sponsor-identified immune-related adverse events (iraes) of any grade occurred in eight (28.6%) patients. the most common sponsor-identified iraes regardless of attribution were autoimmune hepatitis, colitis, hypothyroidism, and pneumonitis (each 7.1%). • grade ≥3 sponsor-identified iraes were observed in one (3.6%) patient. the only grade ≥3 sponsor-identified irae was colitis (3.6%). • median kaplan–meier estimation of pfs was 8.3 months (95% ci, 3.6–19.5) (figure 4). interim analysis of phase 2 results for cemiplimab in patients with metastatic basal cell carcinoma (mbcc) who progressed on or are intolerant to hedgehog inhibitors (hhis) karl d. lewis,1 ketty peris,2 aleksandar sekulic,3 alexander j. stratigos,4 lara dunn,5 zeynep eroglu,6 anne lynn s. chang,7 michael r. migden,8 siyu li,9 suk-young yoo,9 kosalai mohan,10 ebony coates,10 emmanuel okoye,10 jean-françois baurain,11 oliver bechter,12 axel hauschild,13 marcus o. butler,14 leonel hernandez-aya,15 lisa licitra,16 rogerio i. neves,17 emily s. ruiz,18 frank seebach,10 israel lowy,10 timothy bowler,10 matthew g. fury10 1division of medical oncology, university of colorado hospital, aurora, co, usa; 2institute of dermatology, catholic university of the sacred heart, rome, italy and fondazione policlinico universitario a. gemelli-irccs, rome, italy; 3department of dermatology, arizona mayo clinic, scottsdale, az, usa; 4department of dermatology-venereology, andreas sygros hospital-national and kapodistrian university of athens, athens, greece; 5department of medicine, head and neck medical oncology, memorial sloan kettering cancer center, new york, ny, usa; 6department of cutaneous oncology, moffitt cancer center, tampa, fl, usa; 7department of dermatology, stanford university school of medicine, redwood city, ca, usa; 8departments of dermatology and head and neck surgery, university of texas md anderson cancer center, houston, tx, usa; 9regeneron pharmaceuticals, inc., basking ridge, nj, usa; 10regeneron pharmaceuticals, inc., tarrytown, ny, usa; 11university catholic of louvain, brussels, belgium; 12department of general medical oncology, university hospitals, leuven, belgium; 13department of dermatology, schleswig-holstein university hospital, kiel, germany; 14princess margaret cancer centre, university of toronto, toronto, ontario, canada; 15division of medical oncology, washington university school of medicine, st. louis, mo, usa; 16medical oncology head and neck cancer department, fondazione irccs instituto nazionale dei tumori, milan, italy; 17penn state cancer institute, hershey, pa, usa; 18department of dermatology, dana-farber cancer institute, boston, ma, usa presented at the 2021 winter clinical dermatology conference, january 16–24, virtual conference (encore of sitc 2020 poster presentation). 101102042_cobi_pop_pk_l1a copies of this poster obtained through this qr code are for your personal use only and may not be reproduced without permission from the authors. scan to download a reprint of this poster. copyright © 2021. all rights reserved. introduction • ad is a chronic inflammatory skin disease; patients with ad are at higher risk for other atopic comorbidities, such as food allergies1 • the prevalence of food allergy in ad ranges from 20% to 80% in this population2 – although it is not clear whether the presence of food allergies makes ad more difficult to treat, there is an association between ingestion of food that triggers an allergic reaction and ad exacerbation3 • crisaborole ointment, 2%, is an anti-inflammatory nonsteroidal pde4 inhibitor for the treatment of patients aged ≥3 months (≥2 years of age outside the united states) with mild-to-moderate ad4 – initial regulatory approval was based on the results from 2 identically designed, vehicle-controlled, phase 3 clinical studies: core 1 (nct02118766) and core 2 (nct02118792)5 objective • to ascertain the efficacy and safety of crisaborole for the treatment of ad in patients with or without food allergies in a post hoc pooled analysis from the phase 3 studies core 1 and core 2 methods patients and treatment • core 1 and core 2 were 2 identically designed, randomized, double-blind, vehicle-controlled, phase 3 studies conducted to compare crisaborole and vehicle in patients with ad, per hanifin and rajka criteria,6 who had mild-to-moderate disease per the isga and %bsa of ≥5 (excluding the scalp) • patients were randomly assigned in a 2:1 ratio to receive crisaborole ointment, 2%, or vehicle applied twice daily to all areas affected by ad, except the scalp, for 28 days • patients were not permitted to use any topical agents on ad lesions or rescue medications during the study • for this post hoc analysis, patients were stratified based on their medical history of food allergies outcomes and assessments • the isga, a 5-point physician-reported scale of ad severity,5 was assessed at baseline and weekly thereafter • pruritus severity was assessed using the sps, a validated patient or caregiver-reported 4-point rating scale,7 and reported twice daily (morning and evening) via electronic diary • efficacy outcomes were – proportion of patients who achieved isga success (defined as an isga of clear [0] or almost clear [1] with a ≥2-grade improvement from baseline) at day 29 – proportion of patients who achieved isga clear (0) or almost clear (1) at day 29 – proportion of patients who experienced improvement in sps score (defined as a weekly average sps score ≤1 point with ≥1-point improvement from baseline) at week 4 • safety outcomes that included teaes (all cause and treatment related), serious aes, and aes of special interest (eg, anaphylaxis) were collected throughout the study efficacy and safety of crisaborole in patients with mild-to-moderate atopic dermatitis with and without food allergies michael s. blaiss,1 michael j. cork,2 peter lio,3,4 aharon kessel,5,6 liza takiya,7 john l. werth,7 michael a. o’connell,7 chuanbo zang,7 jonathan m. spergel8 1medical college of georgia, augusta university, augusta, ga, usa; 2sheffield dermatology research, iicd, university of sheffield, sheffield children’s hospital, sheffield, united kingdom; 3northwestern university feinberg school of medicine, chicago, il, usa; 4chicago integrative eczema center, chicago, il, usa; 5bnai zion medical center, haifa, israel; 6bruce and ruth rappaport faculty of medicine, technion, haifa, israel; 7pfizer inc., collegeville, pa, usa; 8children’s hospital of philadelphia and perelman school of medicine, university of pennsylvania, philadelphia, pa, usa acknowledgments editorial/medical writing support under the guidance of the authors was provided by christopher m. goodwin, phd, at apothecom, san francisco, ca, usa, and was funded by pfizer inc., new york, ny, usa, in accordance with good publication practice (gpp3) guidelines (ann intern med. 2015;163:461-464). disclosures msb has served as an investigator or consultant for pfizer and regeneron/sanofi genzyme. mjc has served as an investigator or consultant for astellas, boots, dermavant, eli lilly, galapagos, galderma, hyphens, johnson & johnson, kymab, l’oreal, leo, menlo therapeutics, novartis, oxagen, perrigo (aco nordic), pfizer, procter & gamble, reckitt benckiser, regeneron/sanofi genzyme, and ucb pharma. pl is a board member of the national eczema association; has served as an advisor or consultant for regeneron/sanofi genzyme, pfizer, galderma, leo, abbvie, eli lilly, la roche posay, pierre fabre, level ex, unilever, menlo therapeutics, theraplex, intraderm, exeltis, aobiome, arbonne, amyris, bodewell, burt’s bees, and kimberly clark; holds stock in altus labs, micreos, and yobee care; has received honoraria from ucb, dermavant, kiniksa, verrica, realm, and johnson & johnson, as well as fees from regeneron/sanofi genzyme and pfizer; and has served on speaker bureaus for regeneron/sanofi genzyme, pfizer, and galderma. ak has served as an investigator or consultant for pfizer, sanofi, takeda, novartis, gsk, rafa, astrazeneca, and kamada and has received honoraria or fees from pfizer, sanofi, takeda, novartis, gsk, rafa, teva, and kamada. jms has served as an investigator or consultant for regeneron/sanofi genzyme, celgene, allakos, novartis, and dbv technology; has served on speaker bureaus for abbot, medscape, and sanofi; and is an associate editor for the annals of allergy, asthma & immunology. lt, jlw, mao, and cz are employees and stockholders of pfizer inc. presented at the 2021 winter clinical dermatology conference; january 16-24, 2021 abbreviations %bsa, percentage of treatable body surface area; ad, atopic dermatitis; ae, adverse event; isga, investigator’s static global assessment; pde4, phosphodiesterase 4; sps, severity of pruritus score; teae, treatment-emergent adverse event. references 1. dharmage sc et al. curr opin allergy clin immunol. 2004;4(5):379-385. 2. werfel t, breuer k. curr opin allergy clin immunol. 2004;4(5):379-385. 3. robison rg, singh am. j allergy clin immunol pract. 2019;7(1):35-39. 4. eucrisa (crisaborole) ointment, 2%, for topical use [package insert]. new york, ny: pfizer labs; april 2020. 5. paller as et al. j am acad dermatol. 2016;75(3):494-503.e496. 6. hanifin jm, rajka g. acta derm venereol. 1980;60(92):44-47. 7. yosipovitch g et al. itch. 2018;3:e13. this study was funded by pfizer inc. results patients • in the pooled study population, 1016 patients received crisaborole and 506 received vehicle – among them, 251 reported a past medical history of food allergies and 1271 did not have a past medical history of food allergies – baseline demographics were generally similar between treatment arms and between those who did and those who did not have food allergies – regarding baseline disease characteristics, for those with a past medical history of food allergies, a relatively greater proportion (1) used systemic corticosteroids previously, (2) used antihistamines concurrently, (3) had moderate ad per isga at baseline, and (4) had greater %bsa involvement with ad lesions (table 1) table 1. baseline demographics and disease characteristics in patients with and patients without food allergies demographic or characteristic history of food allergies no history of food allergies vehicle n=99 crisaborole n=152 vehicle n=407 crisaborole n=864 age, y mean (sd) median (min, max) 8.3 (5.9) 8.0 (2, 36) 10.8 (10.1) 8.0 (2, 57) 13.0 (12.5) 10.0 (2, 79) 12.6 (12.5) 9.0 (2, 79) female, % (n) 51.5 (51) 45.4 (69) 56.5 (230) 57.5 (497) white, % (n) 62.6 (62) 61.2 (93) 60 (244) 60.7 (524) %bsa mean (sd) median (min, max) 23.4 (20.9) 16.0 (5, 90) 23.2 (21.9) 15.0 (5, 90) 16.9 (16.1) 10.0 (5, 90) 17.5 (17.1) 10.0 (5, 95) isga, % (n) mild (2) moderate (3) 21.2 (21) 78.8 (78) 29 (44) 71.1 (108) 42.3 (172) 57.7 (235) 40.4 (349) 59.6 (515) sps, % (n) none (0) mild (1) moderate (2) severe (3) 0 20.2 (20) 33.3 (33) 30.3 (30) 3.3 (5) 16.5 (25) 34.9 (53) 30.3 (46) 4.7 (19) 24.3 (99) 32.9 (134) 26 (106) 3.5 (30) 23.6 (204) 32.2 (278) 30.3 (262) prior use of systemic corticosteroids,a % (n) 44.4 (44) 44.7 (68) 31.7 (129) 28.1 (243) concurrent use of antihistamines, % (n) 49.5 (49) 48.7 (74) 20.9 (85) 19.8 (171) awithin 90 days before starting study treatment. efficacy • the proportion of patients who achieved isga success at day 29 was significantly greater in the crisaborole-treated group than in the group receiving vehicle, regardless of past medical history of food allergies (figure 1) • similarly, in patients with or without food allergies, a significantly greater proportion of crisaborole-treated patients achieved isga clear or almost clear at day 29 than those given vehicle (figure 2) • at week 4, a numerically greater proportion of patients with or without history of food allergies in the crisaborole group than in the vehicle group achieved improvement in sps score; however, it was only statistically significant in the patients without history of food allergies (figure 3) figure 1. proportion of patients who achieved isga successa at day 29 0 10 20 30 40 50 60 70 80 90 100 p ro po rt io n of p at ie nt s, % (9 5% c i) history of food allergies no history of food allergies p=0.01 p=0.001 17.0 23.131.3 32.3 vehicle crisaborole aisga success defined as isga of clear or almost clear with ≥2-grade improvement from baseline. figure 2. proportion of patients who achieved isga clear or almost clear at day 29 0 10 20 30 40 50 60 70 80 90 100 p ro po rt io n of p at ie nt s, % (9 5% c i) history of food allergies no history of food allergies vehicle crisaborole p=0.003 p<0.0001 22.4 38.540.7 51.8 figure 3. proportion of patients who achieved improvement in spsa score at week 4 0 10 20 30 40 50 60 70 80 90 100 p ro po rt io n of p at ie nt s, % (9 5% c i) history of food allergies no history of food allergies vehicle crisaborole p=0.1 p<0.0001 16.9 21.927.4 37.3 aimprovement in sps score defined as weekly average sps score ≤1 point with a ≥1-point improvement from baseline. safety • the safety profile was generally similar between patients with food allergies and those without food allergies • among patients with food allergies, 61 crisaborole-treated patients (40.1%) and 40 vehicle-treated patients (40.8%) experienced at least 1 all-cause teae – among crisaborole-treated patients with food allergies, 22 (14.5%) experienced a mild teae, 37 (24.3%) experienced a moderate teae, and 2 (1.3%) experienced a severe teae • individual teaes were infrequent (table 2) • the most common treatment-related teae in patients with food allergies and those without food allergies (crisaborole vs vehicle) was application site pain (7.2% vs 3.1% and 4.0% vs 0.7%, respectively) • 1 crisaborole-treated patient with food allergies experienced a serious teae (pneumonia, 0.7%), and no patients (0%) given vehicle experienced a serious teae; the serious teae was not considered related to treatment • no anaphylaxis was reported in any group table 2. most common (in >2% patients) teaes (all cause) in patients with and patients without food allergies history of food allergies no history of food allergies vehicle n=98 crisaborole n=152 vehicle n=401 crisaborole n=860 ae (all cause), % (n) application site pain upper respiratory tract infection viral upper respiratory tract infection pyrexia eczema infected cellulitis staphylococcal skin infection asthma cough nasal congestion 3.1 (3) 1.0 (1) 1.0 (1) 3.1 (3) 1.0 (1) 2.0 (2) 2.0 (2) 1.0 (1) 5.1 (5) 2.0 (2) 7.2 (11) 5.3 (8) 2.0 (3) 2.6 (4) 2.0 (3) 0.7 (1) 0.7 (1) 2.6 (4) 1.3 (2) 3.3 (5) 0.7 (3) 4.0 (16) 2.5 (10) 1.2 (5) 0.2 (1) 0.2 (1) 0.7 (3) 0 1.0 (4) 0 4.0 (34) 3.0 (26) 2.7 (23) 2.3 (20) 0.1 (1) 0.1 (1) 0 0.5 (4) 1.6 (14) 0.5 (4) teaes of special interest, % (n) anaphylaxis 0 0 0 0 limitations • these post hoc analyses were not powered to detect treatment differences in food allergy subgroups; therefore, additional studies are necessary to confirm these results • the core-1 and core-2 studies were not specifically designed to evaluate crisaborole effects on food allergies conclusions • regardless of whether patients have food allergies, crisaborole is effective in treating mild-to-moderate symptoms of ad • the safety profile was generally similar between patients with food allergies and those without food allergies; no new safety signals were observed • crisaborole should be considered for management of ad in patients with or without a history of food allergies characteristics of patients with a complete response treated with dabrafenib + trametinib combination therapy: findings from pooled combi-d and combi-v 5-year analysis caroline robert,1 jean jacques grob,2 daniil stroyakovskiy,3 boguslawa karaszewska,4 axel hauschild,5 evgeny levchenko,6 vanna chiarion sileni,7 jacob schachter,8 claus garbe,9 igor bondarenko,10 paul nathan,11 antoni ribas,12 michael a. davies,13 keith flaherty,14 paul burgess,15 monique tan,16 eduard gasal,16 dirk schadendorf,17 georgina v. long18 1gustave roussy and paris-sud-paris-saclay university, villejuif, france; 2aix-marseille university, marseille, france; 3moscow city oncology hospital, moscow, russia; 4przychodnia lekarska komed, konin, poland; 5university hospital schleswig-holstein, kiel, germany; 6petrov research institute of oncology, st petersburg, russia; 7melanoma oncology unit, veneto institute of oncology iov-irccs, padova, italy; 8ella lemelbaum institute for immuno-oncology and melanoma, sheba medical center, tel hashomer, and sackler school of medicine, tel aviv university, tel aviv, israel; 9department of dermatology, university of tübingen, tübingen, germany; 10dnipropetrovsk state medical academy, dnipropetrovsk, ukraine; 11mount vernon cancer centre, northwood, uk; 12university of california, los angeles, ca; 13the university of texas md anderson cancer center, houston, tx; 14dana-farber cancer institute/harvard medical school and massachusetts general hospital, boston, ma; 15novartis pharma ag, basel, switzerland; 16novartis pharmaceuticals corporation, east hanover, nj; 17university hospital essen, essen, and german cancer consortium, heidelberg, germany; 18melanoma institute australia, the university of sydney, and royal north shore and mater hospitals, sydney, nsw, australia background • dabrafenib (d) + trametinib (t) has been approved in multiple regions for the treatment of patients with braf v600–mutant unresectable or metastatic melanoma and as adjuvant therapy in patients with resected braf v600–mutant stage iii melanoma1-4 • first-line d+t led to approximately one-third of patients with braf v600e/k–mutant unresectable or metastatic melanoma surviving to ≥ 5 years in pooled combi-d/v analysis5,6 – five-year survival rates were higher in patients with normal lactate dehydrogenase (ldh) levels at baseline (43%) and in patients with normal ldh levels and < 3 organ sites with metastases at baseline (55%) • in pooled analyses, best overall response appeared to be associated with progression-free survival (pfs; figure 1) and overall survival (os; figure 2), with patients achieving complete response (cr) having the best long-term outcomes5,7 – median duration of cr was 36.7 months (95% ci, 24.1 months-not reached [nr])5 – five-year pfs rates were 49% and 19% in patients with cr and the overall population, respectively5 – five-year os rates were 71% and 34% in patients with cr and the overall population, respectively5 • increasing evidence, including recent analyses published by the us food and drug administration at asco 2019, suggests that deeper antitumor responses are associated with longer survival8,9 • we present additional analyses to characterize outcomes and clinical features of patients who achieved cr in phase iii randomized combi-d/v trials to identify those most likely to derive the greatest clinical benefit from first-line d+t therapy figure 1. pfs, according to best response5 best response complete response partial response stable disease p f s p ro b a b ili ty 0.0 0.2 0.4 0.6 0.8 1.0 0 6 12 18 24 months since randomization 54 60 66 72 78 42 37 20 1 0 30 36 42 48 109 107 96 88 75 65 57 50 47 no. at risk 2 years, 72% 4 years, 52% 5 years, 49% 3 years, 60% 2 years, 28% 4 years, 17% 5 years, 16% 3 years, 19% 2 years, 6% 4 years, 5% 5 years, 1% 3 years, 6% 27 21 11 1 0274 224 129 87 68 56 43 36 30 2 1 0 0 0130 38 18 13 5 5 5 5 4 complete response partial response stable disease pfs, progression-free survival. figure 2. os, according to best response5 best response complete response partial response stable disease o s p ro b a b ili ty 0 6 12 18 24 months since randomization 54 60 66 72 78 73 72 48 4 0 30 36 42 48 109 108 103 101 97 91 88 82 77 no. at risk 78 73 46 11 0274 266 220 165 134 116 106 95 85 17 15 8 0 0130 99 54 38 32 26 23 22 18 complete response partial response stable disease 2 years, 91% 4 years, 76% 5 years, 71% 3 years, 85% 2 years, 52% 4 years, 35% 5 years, 32% 3 years, 42% 2 years, 29% 4 years, 18% 5 years, 16% 3 years, 22% 0.0 0.2 0.4 0.6 0.8 1.0 os, overall survival. methods • this analysis included treatment-naive patients randomized to d+t in combi-d and combi-v who achieved a confirmed cr and who may or may not have subsequently remained in cr at the data cutoff for the 5-year pooled analysis (combi-d, december 10, 2018; combi-v, october 8, 2018) • an overview of patients included in the pooled analysis is presented in table 1 table 1. overview of overall population and patients with cr included in combi-d/v 5-year analysis study – d+t arm itt population, n patients with cr, na median follow-up for patients with cr (range), mo combi-d (nct01584648) 211 39 68.0 (5.0-73.0) combi-v (nct01597908) 352 70 64.0 (7.0-74.0) pooled 563 109 64.0 (5.0-74.0) cr, complete response; d, dabrafenib; itt, intention to treat; t, trametinib. a includes patients who achieved a confirmed cr and who may or may not have subsequently remained in cr at the data cutoff date. results duration of response • median duration of response (dor) was longer in patients with cr than in patients with partial response (pr; table 2) – in patients with cr, median dor was estimated to be > 60 months in combi-d and was 49.7 months in combi-v (table 2) table 2. dor in patients treated with d+t with cr or pr patients with cr patients with pr combi-d patients, n median dor (95% ci), mo 39 nr (34.5-nr) 107 9.2 (7.2-10.5) combi-v patients, n median dor (95% ci), mo 70 49.7 (27.6-nr) 167 10.8 (8.5-11.3) cr, complete response; d, dabrafenib; dor, duration of response; nr, not reached; pr, partial response; t, trametinib. baseline characteristics in patients with and without cr • a higher proportion of patients who achieved cr had eastern cooperative oncology group performance status (ecog ps) 0, normal ldh levels, and < 3 organ sites with metastases at baseline compared with patients who did not have a cr (table 3) table 3. baseline characteristics in patients with and without cr patients with cra (n = 109) patients without cr (n = 454) age, median (range), years 57 (26-80) 55 (18-91) male, n (%) 50 (46) 269 (59) stage iv m1c, n (%) 42 (39) 318 (70) ecog ps, n (%) 0 ≥ 1 missing 94 (86) 14 (13) 1 (< 1) 309 (68) 141 (31) 4 (< 1) ldh level, n (%) normal > uln missing 98 (90) 11 (10) 0 267 (59) 183 (40) 4 (< 1) ≥ 3 disease sites, n (%) 17 (16) 258 (57) sum of lesion diameters, median, mm 34.0 69.0 cr, complete response; ecog ps, eastern cooperative oncology group performance status; ldh, lactate dehydrogenase; uln, upper limit of normal. a includes patients who achieved cr and who may or may not have subsequently remained in cr at the data cutoff date, including those who were subsequently withdrawn from study or lost to follow-up prior to documented progression. patient disposition • at the time of this analysis, 41% of patients with cr were still receiving d+t or had entered follow-up (table 4) • of 109 patients with cr, 55 (50%) had ongoing cr at the data cutoff date table 4. disposition of patients with cr n (%) patients with cr (n = 109) died 31 (28) ongoing on treatment in follow-up 45 (41) 21 (19) 24 (22) withdrawn from study study closed consent withdrawn loss to follow-up investigator discretion 33 (30) 23 (21) 5 (5) 3 (3) 2 (2) cr, complete response. treatment status in patients who achieved cr • median time to cr was 5.6 months (95% ci, 4.0-7.3 months) • of 109 patients who achieved a cr, 88 (81%) discontinued d and/or t • the most common reason for discontinuation of d or t was disease progression (table 5) – a higher proportion of patients who had a pr discontinued d or t due to disease progression (≈ 72%) compared with patients who achieved a cr (≈ 42%) table 5. overview of reasons for discontinuation of d or t in patients who achieved cr n (%) d (n = 88) t (n = 88) disease progression 38 (43) 36 (41) adverse events 20 (23) 23 (26) patient/proxy decision 13 (15) 12 (14) study closed 11 (13) 12 (14) investigator discretion 5 (6) 4 (5) loss to follow-up 1 (1) 1 (1) cr, complete response; d, dabrafenib; t, trametinib. • of 109 patients who achieved a cr, 46 (42%) discontinued d and/or t while in response – adverse events were the most common reason for discontinuation of d (35%) or t (39%) in patients still in cr (figure 3) figure 3. reasons for stopping (a) dabrafenib or (b) trametinib in patients who remained in cr at time of discontinuation (n = 46) adverse events 35% patient/proxy decision 24% study closed 24% investigator discretion 11% disease progressiona 4% loss to follow-up 2% adverse events 39% patient/proxy decision 24% study closed 24% investigator discretion 9% disease progressiona 2% loss to follow-up 2% a b cr, complete response. a treatment discontinued before the date of disease progression, but disease progression occurred prior to the data cutoff date. baseline characteristics in patients whose disease did or did not progress after cr • baseline characteristics were similar overall in patients whose disease did or did not progress after they achieved a cr (table 6) patterns of progression • of 109 patients with cr, 54 (50%) had disease progression and 48 had new lesions – common sites of new lesions included the central nervous system (cns; 54%), lung (17%), lymph nodes (17%), and skin/subcutaneous tissue (13%) • in patients with cr whose disease progressed, the patterns of progression were similar to those observed in the overall population (n = 359) – in the overall population, common sites of progression included the cns (40%), lung (21%), lymph nodes (21%), and liver (14%) – the cns was the only site of new lesions in 19 of 26 patients (73%) with cr and 104 of 144 patients (72%) in the overall population table 6. baseline characteristics in patients with cr whose disease did or did not progress patients with cr whose disease progressed (n = 54) patients with cr whose disease did not progress (n = 55) age, median (range), years 56 (26-80) 57 (31-77) male, n (%) 26 (48) 24 (44) stage iv m1c, n (%) 20 (37) 22 (40) ecog ps, n (%) 0 ≥ 1 missing 47 (87) 7 (13) 0 47 (85) 7 (13) 1 (2) ldh, n (%) normal > uln 47 (87) 7 (13) 51 (93) 4 (7) ≥ 3 disease sites, n (%) 10 (19) 7 (13) sum of lesion diameters, median, mm 35.0 33.0 cr, complete response; ecog ps, eastern cooperative oncology group performance status; ldh, lactate dehydrogenase; uln, upper limit of normal. subsequent therapy • common posttreatment anticancer therapy for patients who achieved a cr included targeted therapy (23%), and anti–programmed death receptor 1 (pd-1; 19%), and anti–cytotoxic t-lymphocyte–associated antigen 4 immunotherapies (16%) (table 7) table 7. summary of posttreatment anticancer therapy n (%) patients with cr (n = 109) any subsequent therapy 43 (39) radiotherapy 21 (19) surgery 5 (5) targeted therapy dabrafenib trametinib vemurafenib cobimetinib binimetinib encorafenib 25 (23) 20 (18) 14 (13) 6 (6) 4 (4) 2 (2) 2 (2) immunotherapy ipilimumab pembrolizumab nivolumab 28 (26) 17 (16) 13 (12) 8 (7) chemotherapy 10 (9) cr, complete response. conclusions • pooled analysis of the combi-d/v studies showed that patients who were treated with d+t and achieved cr (19%) demonstrated improved survival outcomes compared with the overall population – crs showed durability, with a median duration of 36.7 months and 55 patients (50%) still in cr as of the last disease assessment – median dor was longer in patients with cr than in patients with pr • a higher proportion of patients who achieved cr had ecog ps 0, normal ldh levels, and < 3 organ sites with metastases at baseline compared with patients without cr • select baseline factors may be useful for identifying patients with advanced braf v600e/k–mutant melanoma who may derive the greatest clinical benefit from first-line d+t combination therapy, although additional analyses are needed for validation • increasing evidence suggests that cr is associated with long-term benefit.8,9 to further improve outcomes, a trial combining d+t with the anti–pd-1 inhibitor spartalizumab in patients with metastatic braf v600–mutant melanoma (nct02967692) is ongoing acknowledgments the authors thank the patients and their families for their participation. we also thank all investigators and site staff for their contributions. statistical support needed to conduct this post hoc analysis was provided by novartis pharmaceuticals corporation. we also thank maurizio voi, md (novartis pharmaceuticals corporation), for guidance and critical review and jorge j. moreno-cantu, msc, phd (novartis pharmaceuticals corporation), for editorial assistance. we thank zareen khan, phd, from articulatescience llc, for medical editorial assistance with this presentation, which was funded by novartis pharmaceuticals corporation, east hanover, nj, in accordance with good publication practice (gpp3) (https://www.ismpp.org/gpp3) guidelines and international committee of medical journal editors recommendations. this study was sponsored by glaxosmithkline; dabrafenib and trametinib are assets of novartis ag as of march 2, 2015. references 1. tafinlar (dabrafenib) [package insert]. east hanover, nj: novartis pharmaceuticals corporation; 2020. 2. mekinist (trametinib) [package insert]. east hanover, nj: novartis pharmaceuticals corporation; 2020. 3. tafinlar (dabrafenib) [summary of product characteristics]. camberley, uk: novartis pharmaceuticals uk ltd; 2020. https://www.ema.europa.eu/en/documents/productinformation/tafinlar-epar-product-information_en.pdf. accessed july 31, 2020. 4. mekinist (trametinib) [summary of product characteristics]. camberley, uk: novartis pharmaceuticals uk ltd; 2020. https://www.ema.europa.eu/en/documents/productinformation/mekinist-epar-product-information_en.pdf. accessed july 31, 2020. 5. robert c, et al. n engl j med. 2019;381:626-636. 6. nathan p, et al. j clin oncol. 2019;37:abstract 9507. 7. long gv, et al. lancet oncol. 2016;17:1743-1754. 8. osgood c, et al. j clin oncol. 2019;37:abstract 9508. 9. mccoach ce, et al. ann oncol. 2017;28:2707-2714. poster presentation at the fall clinical dermatology conference; october 29-november 1, 2020; las vegas, nv. this was previously presented at the 16th international congress of the society for melanoma research. text: q3d0e1 to: 8nova (86682) us only +18324604729 north, central and south americas; caribbean; china +447860024038 uk, europe, and russia +46737494608 sweden and europe scan this qr code to download a copy of the poster copies of this poster obtained through quick response (qr) code are for personal use only and may not be reproduced without written permission of the authors. visit the web at: http://novartis.medicalcongressposters.com/default.aspx?doc=3d0e1 http://novartis.medicalcongressposters.com/default.aspx?doc=3d0e1 skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 137 rising derm stars® hairy legs revisited: peroneal alopecia katherine glaser md1, kenneth tomecki md 1department of dermatology, cleveland clinic, cleveland, oh background/objectives: peroneal alopecia (pa), also called anterolateral leg alopecia, is a common, often underreported and understudied type of hair loss in middle-aged men. it presents as large sharply demarcated alopetic patches symmetrically over the anterolateral aspects of the legs, reflecting the distribution of the peroneal nerve. the underlying etiology is poorly understood. suggested associations include friction from tight fitting clothing, androgenetic alopecia, thyroid disease, diabetes, and peripheral vascular disease. this study aims to review these reported associations in our subset of patients. methods: we conducted a cross-sectional study in our outpatient dermatology clinic. 50 consecutive men aged ≥ 50 years who presented for routine full body skin exams were included. routine skin examination was performed including evaluation for androgenetic alopecia using the norwoodhamilton scale. medical history included inquiry of known diabetes, peripheral vascular disease or cardiac disease, and family history of androgenetic alopecia. we asked all patients if they wore tight fitting socks or clothing on a regular basis. results: we detected pa in 42% of men (n=21). personal and family history of androgenetic alopecia was common, 46% and 48% respectively. in patients with pa, androgenetic alopecia occurred in 57% (n=12) compared to the 37% (n=11) without pa. the prevalence of diabetes and vascular disease was comparable to the general population and occurred similarly in those with and without pa. regular use of tight fitting socks was reported in only 5 patients with the majority (n=4) found to have pa, though these patients often hypothesized this to be the cause of their hair loss. (see table 1) limitations: small sample size and the selected age cut-off may not capture the true prevalence of this entity. the study does not incorporate dermoscopy or histopathology which can be helpful in distinguishing types of alopecia. conclusion: pa is an extremely common form of hair loss in middle-aged men. this study represents the largest study of pa to date. we failed to identify any clear correlation in this study though personal and family history of androgenetic alopecia was a common association. we plan to extend our study and examine such patients further to determine a statistically significant pathogenesis. skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 138 table 1: incidence of peroneal alopecia. present n=21 (42%) absent n=29 (58%) total n=50 androgenetic alopecia 12 (57) 11 (37) 23 (46) fhx androgenetic alopecia 13 (61) 11 (37) 24 (48) diabetes 4 (19) 3 (10) 7 (14) vascular disease 6 (29) 9 (31) 15 (30) tight fitting socks 4 (19) 1 (3) 5 (10) fhx, family history of references: 1. brueseke tj, macrino s, miller jj. lack of lower extremity hair not a predictor for peripheral arterial disease. arch dermatol. 2009;145(12):1456-7 2. gupta sn, shaw jc. anterolateral leg alopecia revisited. cutis 2002;70:215-6 3. jakhar d, kaur i. frictional (sock) alopecia of the legs: trichoscopy as an aid. int j trichol 2018;10:129-30 4. shetty vm, pai sb, pai k, jenson jj. anterolateral leg alopecia: unknown entity or yet underreported? int j dermatol. 2018 sep. [epub ahead of print] pmid: 30264393 5. trueb rm, lee ws. “diagnosis and treatment.” male alopecia: guide to successful management. springer international pu, 2016, pp. 75–89 powerpoint presentation presented at 40th annual fall clinical dermatology conference, october 29–november 1, 2020 references 1. griffiths ce, barker jn. lancet 2007;370:263-271. 2. boehncke w-h, schön mp. lancet 2015;386:983-994. 3. papp ka, et al. j drugs dermatol 2020;19:734-740. 4. lebwohl mg, et al. n engl j med 2020;383:229-239. 5. lebwohl m, et al. int j dermatol 2014;53:714-722. 6. strober be, et al. value health 2013;16:1014-1022. 7. strober b, et al. int j dermatol 2016;55:e147-e155. 8. finlay ay, khan gk. clin exp dermatol 1994;19:210-216. leon h. kircik,1 mark g. lebwohl,2 kim a. papp,3 melinda j. gooderham,4 linda stein gold,5 zoe d. draelos,6 steven e. kempers,7 stephen k. tyring,8 lorne e. albrecht,9 marni wiseman,10 laura k. ferris,11 kathleen smith,12 robert c. higham,12 lynn navale,12 howard welgus,12 david r. berk12 1icahn school of medicine at mount sinai, new york, ny, indiana medical center, indianapolis, in, physicians skin care, pllc, louisville, ky, and skin sciences, pllc, louisville, ky, usa; 2icahn school of medicine at mount sinai, new york, ny, usa; 3probity medical research and k papp clinical research, waterloo, on, canada; 4skin centre for dermatology, probity medical research and queen’s university, peterborough, on, canada; 5henry ford medical center, detroit, mi, usa; 6dermatology consulting services, high point, nc, usa; 7minnesota clinical study center, fridley, mn, usa; 8mcgovern medical school, university of texas health science center, houston, tx, usa; 9probity medical research and enverus medical research, surrey, bc, canada; 10probity medical research and skinwise dermatology, winnipeg, mb, canada; 11university of pittsburgh, department of dermatology, pittsburgh, pa, usa; 12arcutis biotherapeutics, inc., westlake village, ca, usa roflumilast cream (arq-151) 0.15% and 0.3% improved burden of signs and symptoms in adults with chronic plaque psoriasis in a phase 2b study introduction • typical signs of plaque psoriasis include erythematous, scaly, well-demarcated plaques frequently associated with pain, itching, or burning that can have a negative effect on quality of life (qol)1,2 • roflumilast cream (arq-151), a potent phosphodiesterase-4 (pde-4) inhibitor, is under investigation as a once-daily topical treatment for patients with chronic plaque psoriasis3,4 • in a randomized, double-blind, phase 2b trial of 331 adults with chronic plaque psoriasis, roflumilast cream administered once daily was superior to vehicle cream and led to achievement of clear or almost clear skin based on investigator global assessment (iga) at week 6 (figure 1)4 • the effect of roflumilast cream on various patient-reported outcome (pro) measures, including psoriasis sign and symptom burden and qol, was assessed as a secondary outcome in the phase 2b trial4 objective • to assess the effect of roflumilast cream on patient-reported burden of signs and symptoms of psoriasis and on qol methods study design • design: parallel-group, randomized, double-blind, vehicle-controlled phase 2b study (clinicaltrials.gov nct03638258)4 • location: 30 sites in the united states and canada • participants: adult patients (≥18 years) with chronic plaque psoriasis • eligibility: – disease of at least mild severity (score ≥2 on a 5-point iga, assessing plaque thickening, scaling, and erythema; a score of 0 indicates “clear”, 1 “almost clear”, and 4 severe) – score of ≥2 on the modified psoriasis area and severity index (range: 0, no disease; 72, maximal disease) • intervention: roflumilast cream 0.3%, 0.15%, or vehicle; once daily for 12 weeks • primary endpoint: iga status of “clear” or “almost clear” (score 0 or 1) at week 6 in the intent-to-treat population assessments of sign and symptom burden and qol • psoriasis symptom diary (psd)5-7 – total score: severity and impact of psoriasis-related signs and symptoms over the past 24 hours – burden of individual signs and symptoms: stinging (psd item 4), burning (psd item 6), skin cracking (psd item 8), pain (psd item 10), and scaling (psd item 12) – each variable scored on a scale from 0 to 10, with higher scores indicating greater burden • dermatology life quality index (dlqi)8 – 10 questions concerning symptoms and feelings, daily activities, leisure, work and study, personal relationships, and treatment in the last week – scored on a scale from 0 (no impairment of life quality) to 30 (maximum impairment) – added mid-study via protocol amendment and completed by a subset of patients results • for the primary endpoint, superior efficacy was demonstrated for both dose levels of roflumilast cream vs vehicle cream (figure 1)4 conclusions • roflumilast once-daily cream 0.3% and 0.15% showed significant improvement of plaque psoriasis severity measured by achievement of iga “clear” or “almost clear” • roflumilast cream demonstrated improvement in patient-reported burden of psoriasis signs and symptoms and qol • the improvements in sign and symptom burden and qol occurred soon after initiating treatment with both roflumilast cream doses and were maintained through week 12 • roflumilast cream was well-tolerated and application site pain was uncommon and similar to vehicle • assessments of symptom and sign burden and qol were comparable across treatment groups at baseline (table 1) • rapid and statistically significant improvements on the total psd score were observed at weeks 4 through 12 for the 0.3% dose (p≤0.002 vs vehicle) and as early as week 2 for the 0.15% dose (p≤0.014) of roflumilast (figure 2) • statistically significant improvements relative to vehicle were seen in burden of individual patient-reported signs and symptoms of scaling by week 2; stinging, skin cracking, and pain by week 4; and burning by week 6 for both roflumilast doses (figure 3) • mean change in dlqi score from baseline at week 12 was significantly greater for both roflumilast doses vs vehicle (p≤0.036) (figure 4) • treatment-emergent adverse events (aes) were uncommon in this study and were similar across treatment groups (table 2)4 figure 1. patients achieving iga of “clear” or “almost clear” at week 6 (primary endpoint) 28.0% 22.8% 8.3% week 6 pa ti en ts , % (9 5% c i) p<0.001 p=0.00440 30 20 10 0 data are presented for intent-to-treat population. ci: confidence interval; iga: investigator global assessment. table 1. baseline assessments of pro measures mean score (sd) roflumilast 0.3% (n=109) roflumilast 0.15% (n=113) vehicle (n=109) psd, total score 68.9 (41.2) 69.6 (46.2) 75.1 (42.6) psd item 4: stinging 3.9 (3.2) 3.8 (3.3) 4.3 (3.3) psd item 6: burning 3.5 (3.3) 3.5 (3.4) 4.0 (3.2) psd item 8: skin cracking 4.0 (3.3) 4.4 (3.6) 4.7 (3.3) psd item 10: pain 3.3 (3.3) 3.2 (3.4) 3.8 (3.2) psd item 12: scaling 4.9 (3.0) 5.0 (3.4) 5.6 (3.4) dlqi, total scorea 6.7 (5.5) 8.8 (7.2) 8.5 (5.6) data are presented for intent-to-treat population. aassessed for 58 patients in roflumilast 0.3%, 60 in roflumilast 0.15%, and 62 in vehicle treatment group. dlqi: dermatology life quality index; pro: patient-reported outcome; psd: psoriasis symptom diary; sd: standard deviation. figure 2. total psd score over the course of the study data are presented for intent-to-treat population. missing data imputed using linear interpolation and last observation carried forward where linear interpolation was not computationally possible. ls: least squares; psd: psoriasis symptom diary. -50 -45 -40 -35 -30 -25 -20 -15 -10 -5 0 week 2 week 4 week 6 week 8 week 12 ls m ea n ch an ge f ro m ba se lin e in t ot al p sd s co re total psd score i m p r o v e m e n t * * * * * * * * * roflumilast 0.15% (n=113) vehicle (n=109)roflumilast 0.3% (n=109) *nominal p<0.05 vs vehicle figure 3. patient-reported burden of individual psoriasis signs and symptoms data are presented for intent-to-treat population. missing data imputed using linear interpolation and last observation carried forward where linear interpolation was not computationally possible. ls: least squares; psd: psoriasis symptom diary. -3.5 -3.0 -2.5 -2.0 -1.5 -1.0 -0.5 0.0 2 4 6 8 12 2 4 6 8 12 2 4 6 8 12 2 4 6 8 12 2 4 6 8 12 ls m ea n ch an ge f ro m ba se lin e in p sd s co re * * * * week stinging (psd item 4) skin cracking (psd item 8) pain (psd item 10) scaling (psd item 12)burning (psd item 6) * * * * * * * *** * * * * * * * * * * * * ** **** * ** ** ** ** ** * * week weekweekweek roflumilast 0.15% (n=113) vehicle (n=109)roflumilast 0.3% (n=109) *nominal p<0.05 vs vehicle i m p r o v e m e n t figure 4. change from baseline in dlqi scores data are presented for intent-to-treat population. missing data imputed using linear interpolation and last observation carried forward where linear interpolation was not computationally possible. dlqi: dermatology life quality index; ls: least squares. roflumilast 0.15% (n=60) vehicle (n=62)roflumilast 0.3% (n=58) dlqi score -5.0 -4.0 -3.0 -2.0 -1.0 0.0 week 2 week 4 week 6 week 8 week 12 ls m ea n ch an ge fr om b as el in e in d lq i s co re * * ** *nominal p<0.05 vs vehicle i m p r o v e m e n t table 2. summary of aes teae, n (%) roflumilast 0.3% (n=109) roflumilast 0.15% (n=110) vehicle (n=107) patients with any teae 42 (38.5) 30 (27.3) 32 (29.9) patients with any treatment-related teae 7 (6.4) 3 (2.7) 7 (6.5) patients with any saea 1 (0.9) 1 (0.9) 2 (1.9) patients who discontinued study due to aeb 1 (0.9) 0 2 (1.9) most common teae (>2% of patients in any group) upper respiratory tract infection (including viral) 9 (8.3) 8 (7.3) 4 (3.7) nasopharyngitis 4 (3.7) 3 (2.7) 4 (3.7) application site pain 2 (1.8) 1 (0.9) 3 (2.8) sinusitis 3 (2.8) 0 0 urinary tract infection 0 3 (2.7) 1 (0.9) aroflumilast 0.3%: worsening of chest pain in a patient with history of myocardial infarction; roflumilast 0.15%: melanoma (not in treatment area); vehicle group: acute infarction of left basal ganglia, spontaneous miscarriage. broflumilast 0.3%: onset of worsening psoriasis; vehicle: mood swings, contact dermatitis. data are presented for safety population. ae: adverse event; sae: serious adverse event; teae: treatmentemergent adverse event. roflumilast cream, an investigational once-daily topical pde-4 inhibitor, may be an effective, safe, and well-tolerated nonsteroidal topical treatment for chronic plaque psoriasis with early onset of action acknowledgements • this study was supported by arcutis biotherapeutics, inc. • thank you to the investigators and their staff for their participation in the trial • we are grateful to the study participants and their families for their time and commitment • writing support was provided by aleksandra adomas, phd, cmpp, touch scientific, philadelphia, pa, and funded by arcutis biotherapeutics, inc. disclosures lhk, mgl, kap, mjg, lsg, zdd, sek, skt, lea, mw, and lkf: investigator, consultant, and/or advisory board member for arcutis biotherapeutics, inc. zdd has received grant support from arcutis biotherapeutics, inc. ks, rch, ln, and drb: employees of arcutis biotherapeutics, inc. hw has a patent application relevant to this work. scan qr code for a digital copy of this poster • more patients discontinued the study due to an ae in the vehicle group vs the roflumilast groups • rates of application site pain were low and similar to vehicle • 97% of aes were rated mild or moderate roflumilast 0.15% (n=113) vehicle (n=109) roflumilast 0.3% (n=109) roflumilast cream (arq-151) 0.15% and 0.3% improved burden of signs and symptoms in adults with chronic plaque psoriasis in a phase 2b study << /ascii85encodepages false /allowpsxobjects false /allowtransparency false /alwaysembed [ true ] /antialiascolorimages false /antialiasgrayimages false /antialiasmonoimages false /autofiltercolorimages true /autofiltergrayimages true /autopositionepsfiles true /autorotatepages 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(http://www.color.org) /pdfxsetbleedboxtomediabox false /pdfxtrapped /false /pdfxtrimboxtomediaboxoffset [ 0 0 0 0 ] /parsedsccomments true /parsedsccommentsfordocinfo true /parseiccprofilesincomments true /passthroughjpegimages true /preservecopypage true /preservedicmykvalues true /preserveepsinfo true /preserveflatness false /preservehalftoneinfo false /preserveopicomments false /preserveoverprintsettings true /startpage 1 /subsetfonts true /transferfunctioninfo /apply /ucrandbginfo /remove /useprologue false /srgbprofile (srgb iec61966-2.1) >> setdistillerparams << /hwresolution [2400 2400] /pagesize [612.000 792.000] >> setpagedevice skin march 2018 volume 2 issue 2 copyright 2018 the national society for cutaneous medicine 111 original research prospective, multicenter clinical impact evaluation of a 31-gene expression profile test for management of melanoma patients larry d. dillon md a , joseph e. gadzia md b , robert s. davidson md c , michael mcphee md d , kyle r. covington phd e , robert w. cook phd e , clare johnson rn e , federico a. monzon md e , eric d. milanese mms pa-c f , john t. vetto md f , abel d. jarrell md g , martin d. fleming md h a larry d. dillon surgical oncology and general surgery, colorado springs, co b kansas medical clinic, pa, topeka, ks c morton plant mease healthcare, safety harbor, fl d promedica physicians surgical oncology, sylvania, oh e castle biosciences, inc., friendswood, tx f oregon health and science university, portland, or g northeast dermatology associates, p.c., beverly, ma h the university of tennessee health science center, memphis, tn abstract objective: a 31-gene expression profile (gep) test that has been clinically validated identifies melanoma patients with low (class 1) or high (class 2) risk of metastasis based on primary tumor biology. this study aimed to prospectively evaluate the test impact on clinical management of melanoma patients. methods: physicians at 16 dermatology, surgical or medical oncology centers examined patients to assess clinical features of the primary melanoma. recommendations for clinical follow-up and surveillance were collected. following consent of the patient and performance of the gep test, recommendations for management were again collected, and preand post-test recommendations were assessed to determine changes in management resulting from the addition of gep testing to traditional clinicopathologic risk factors. results: post-test management plans changed for 49% (122 of 247) of cases in the study when compared to pre-test plans. thirty-six percent (66 of 181) of class 1 cases had a management change, compared to 85% (56 of 66) of class 2 cases. gep class was a significant factor for change in care during the study (p<0.001), with class 1 accounting for 91% (39 of 43) of cases with decreased management intensity, and class 2 accounting for 72% (49 of 68) of cases with increases. conclusions: physicians used test results to guide risk-appropriate changes that match the biological risk of the tumor, including directing more frequent and intense surveillance to high-risk, class 2 patients. skin march 2018 volume 2 issue 2 copyright 2018 the national society for cutaneous medicine 112 current guidelines for cutaneous melanoma indicate that patient management and intensity of surveillance should ultimately be tailored to an individual patient’s probability of recurrence, as this is the most important factor to consider in determining follow-up and management plans. 1 however, patients traditionally classified as low-risk by clinicopathologic staging factors (ajcc stage i-ii), and thus managed as low-risk, contribute to the majority of recurrences and deaths from stage i-iii melanoma. 2-4 thus, identification of stage i and ii patients with biologically aggressive melanomas is an unmet and clinically important need. intensive surveillance in high-risk patients has been shown to identify 80% of metastases before they become symptomatic, allowing for identification of patients with low burden of metastatic disease. 5-7 multiple studies have demonstrated greater efficacy for targeted and immunotherapies in melanoma when disease burden is low, which supports the rationale for identifying those patients at highest risk of recurrence as early as possible to maximize therapeutic benefit. 8-12 molecular biomarkers can assess risk in melanoma patients by providing additional information that is independent of the clinicopathologic features currently used in staging. the decisiondx-melanoma gene expression profile (gep) test is an analytically and clinically validated prognostic test that predicts individual risk of recurrence. 13-16 the test provides an accurate prognosis of metastasis risk, identifying melanoma tumors as low risk (class 1) or high risk (class 2) based on the expression of 31 genes from the primary melanoma tumor such that stage i and ii patients with class 1 tumors have a risk of metastasis and death from melanoma that is similar to the risk of a stage ia tumor and class 2 tumors have a risk of metastasis and death from melanoma that is similar to a stage iii tumor. 13,14 aside from analytical and clinical validity, a critical evaluation of a prognostic test is to determine its clinical utility, which can be demonstrated by the impact of the test on changes in patient management. clinical decision impact of the 31-gene expression profile test has been previously evaluated in a multicenter study which documented posttest changes in management in 53% of 156 cutaneous melanoma patients who were consecutively tested. 17 to further assess the clinical utility of the gep test, we undertook a study to evaluate and compare clinical management plans in a prospective design, including initial workup, follow-up intervals, and referral patterns, established by physicians prior to and after gep testing. data collection data was collected following irb approval at 16 participating dermatology, medical oncology and surgical oncology centers. at the time of the initial evaluation, prior to gep testing and after patient consent, the treating physician assessed each patient’s baseline characteristics, including breslow thickness, ulceration status and mitotic rate. the physician’s pre-test recommendations for clinical visits, laboratory tests (labs), introduction methods skin march 2018 volume 2 issue 2 copyright 2018 the national society for cutaneous medicine 113 imaging, adjuvant treatment discussion, referral to surgical or medical oncology, and sentinel lymph node biopsy (slnb) were collected. at the subsequent visit following receipt of the gep test result, the physician’s management recommendations were again collected to capture any changes in management. all data were entered into a secure electronic case report form. at the time the database was locked for analysis (september 2017), 269 patients were enrolled in the study. of those, 247 were stage i or ii at the time of patient consent, completed study participation including pre and post-test office visits, and were included for this analysis. clinical characteristics of the cohort are presented in table 1. table 1. clinical characteristics at diagnosis. clinical characteristics overall n=247 median age (range), years 63 (19-94) t stage t1 115 (47%) t2 66 (27%) t3 33 (13%) t4 18 (7%) not assessed 12 (6%) breslow thickness median (range), mm 1.1 (0.1-18.0) ≤1 mm 121 (49%) >1 mm 126 (51%) mitotic index <1/mm 2 87 (35%) ≥1/mm 2 160 (65%) ulceration absent 204 (83%) present 43 (17%) sentinel lymph node status negative 149 (60%) positive 18 (8%) unassessed 80 (32%) site trunk 77 (31%) extremity 124 (50%) head and neck 43 (17%) gep result class 1 181 (73%) class 2 66 (27%) skin march 2018 volume 2 issue 2 copyright 2018 the national society for cutaneous medicine 114 statistical analysis the study was powered to capture a 20% change in management for enrolled patients. it was assumed that 20% of the patients would be high risk according to the gep test, and that 50% of physicians would agree with the high-risk test result. based on these assumptions, enrollment of 250 patients was expected to achieve the desired rate of change with 100% power to reject the null hypothesis and a 95% confidence interval of 9.9%. documented changes in management parameters were categorized as increased, decreased or unchanged based on comparison of management plans before and after the gep test. due to the flexibility in national guidelines for the frequency of follow-up and imaging, all differences specified between preand post-gep responses were considered as changes of management. for comparison of preand post-test management decisions, fisher’s exact, chi-squared or f tests were used where appropriate. summary and statistical analysis was performed in r version 3.3.2 (university of auckland, nz). cohort demographics a total of 247 stage i-ii cases were examined to compare patient management practices prior to receiving gep results and after receiving gep results. table 2 lists clinical features of the cohort according to the specialty of the physician providing care. dermatology groups contributed 74 cases, 7 cases were enrolled by medical oncology groups, and surgical oncology groups contributed 166 cases. we assessed whether pathological features of the tumor were associated with provider type. as expected, breslow thickness (bt) and gep class 2 were observed more frequently in cases from surgical oncology providers compared to dermatology (p<0.05 for gep). overall, there was no statistical difference in ulceration between patients enrolled by dermatology, medical oncology and surgical oncology groups (p>0.3) but mitotic rate was significantly different between each (p<0.001). within the cohort, 68% (167 of 247) of patients underwent a slnb after consent for inclusion in the study. eigthy-nine percent (149 of 167) of those patients had a negative slnb outcome, and 11% (18 of 167) had a positive outcome. as 13 of 18 node positive patients were clinical stage iiia, this means that the slnb procedure may have changed management by up to 8%. comparatively, 81% (39 of 48) of the sln-negative/class 2 patients had an increase in the intensity of management, reflecting guidance of patient care based on tumor biology. impact of gep on patient management comparing pre-test management plans to post-test management plans, 49% (122 of 247) of all cases had a change in management after receipt of the gep test results, including 36% (66 of 181) of class 1 and 85% (56 of 66) of class 2 cases. overall, 43 cases only had a decrease in the level or intensity of care, 68 cases only had an increase, and 125 cases had no change (table 3). eleven cases had simultaneous increases and decreases in the level of care (i.e., addition of one modality with removal of another). class 1 accounted for 39 (91%) cases with decreases in management results skin march 2018 volume 2 issue 2 copyright 2018 the national society for cutaneous medicine 115 intensity, while class 2 accounted for 49 (72%) cases with increases. gep class was a significant predictor of change in care (p<0.001). table 2. clinical features across physician specialties. feature dermatology n=74 surgical oncology n=166 medical oncology n=7 breslow a 0.6 (0.1-10.3) 1.3 (0.1-8.0) 1.1 (0.2-18.0) ulceration b absent 65 (88%) 133 (80%) 6 (86%) present 9 (12%) 33 (20%) 1 (14%) mitosis b * <1/mm 2 38 (51%) 45 (27%) 4 (57%) ≥1/mm 2 36 (49%) 121 (73%) 3 (43%) gep class b * class 1 60 (81%) 114 (69%) 7 (100%) class 2 14 (19%) 52 (31%) 0 (0%) a median (range), b count (percent), *p<0.05, fisher’s exact test table 3. number of cases increasing or decreasing intensity of management by gep class. gep class decrease increase no change class 1 39 19 115 p<0.001 class 2 4 49 10 table 4 lists the changes observed in the study according to each management modality assessed. the modalities that were changed most frequently were imaging, office visits and referrals. of 68 cases with changes in imaging, 42 were class 2 patients who had the intensity of imaging increase, either at more frequent intervals or with a more intense method of imaging (i.e., pet/ct rather than chest xskin march 2018 volume 2 issue 2 copyright 2018 the national society for cutaneous medicine 116 ray). eleven patients with changes in imaging were risk-appropriate decreases in either the frequency or modality of imaging (i.e., chest x-ray at baseline rather than yearly pet/ct and brain mri) corresponding with a class 1 result. table 4. frequency of each modality of change in patients with decreases or increases in intensity of clinical management. class 1 class 2 decrease increase decrease increase p value* visits 28 13 1 28 <0.001 imaging 11 11 4 42 <0.001 labs 5 6 3 22 0.04 referral 11 13 3 14 0.1 *fisher’s exact test the clinical utility of a diagnostic or prognostic test, measured by the impact on patient management decisions, is a critical measure of the test’s clinical value. in this prospective analysis of the clinical utility of the 31-gene gep test, risk assessment based on test results impacted follow-up plans of 49% of the cases. additionally, the majority of reported management changes were in a risk-appropriate direction, with 91% of decreases in care provided to lowrisk class 1 patients and 72% of increases in care provided to high-risk class 2 patients. thus, gep test results informed physicians to make individualized management decisions based on biological risk, as determined by the gep test, all within the context of established practice guidelines. the change of 49% with the gep test compares favorably to the 8% change observed with slnb. three clinical use studies with different design methodologies have previously been reported, including a prospectively tested, multicenter chart review comparing pre-test to post-test management plans, an intended use survey also comparing pre-test to posttest management plans, and analysis of a prospectively tested single center population evaluating adherence to the center’s management protocol following incorporation of the gep test. 17-19 all three studies reported a change in management of 47-53% when the gep test was added to traditional clinicopathologic staging factors (table 5). discussion skin march 2018 volume 2 issue 2 copyright 2018 the national society for cutaneous medicine 117 table 5. previous studies reporting the clinical utility of the 31-gep test. with a change in management of 49%, this prospective, multicenter study confirms the previous studies and showed that the results of the gep test lead to appropriate management changes for i) high-risk, class 2, early stage melanoma patients who would benefit from enhanced surveillance to identify metastatic disease as early as possible; and ii) melanoma patients who are less likely to develop systemic metastasis (class 1) and would benefit from less intense management strategies, as specified by national guideline recommendations. the study also identified a small subset of class 1 patients for whom management strategies were increased. for this subset of patients, the majority had high risk clinicopathologic features (sln-positive, t3/t4 thickness), indicating that physicians chose to manage patients based on the most worrisome risk factor, and that treating physicians considered both clinical and molecular data when planning follow-up and surveillance. the result of the gep impact on care is a potential improvement in net health outcomes through the addition of appropriate management plans. per national guidelines, management plans for low-risk patients include routine clinical exams only, and management plans for high-risk patients (stage iib and above) include frequent clinical exams to detect both additional primary skin cancers and locoregional metastasis, and the addition of imaging surveillance to detect distant metastasis as early as possible[20]. accordingly, the most clinically significant management change observed in this study was the increase in the intensity of imaging for those patients being identified as highrisk class 2 by the gep test, given that a high risk gep class 2 test result predicts a risk of distant metastasis that is similar to a stage iii patient. of the 68 cases with changes in imaging, 42 were class 2 patients who had more frequent imaging intervals or were changed to a more sensitive modality (e.g., pet/ct rather than chest x-ray). two recent studies study design n change in management berger et al. cmro, 2016  prospectively tested patients  retrospective chart review  multicenter 163 53% farberg et al. jdd, 2017  intended use analysis  physician response 159 47-50% schuitevoerder et al. jdd, 2018  prospectively tested patients  single center 90 52% skin march 2018 volume 2 issue 2 copyright 2018 the national society for cutaneous medicine 118 prospectively evaluated the value of ctbased imaging for identifying distant metastasis in stage ii-iii patients. 5,6,7 both studies found that greater than 75% of distant metastases were detected by imaging, when the patients were asymptomatic, compared to physician or patient detection. considering the growing body of evidence showing that contemporary therapies for melanoma exhibit better efficacy in patients with lower tumor burden, guideline recommended enhanced imaging for earlier detection of metastatic disease is warranted for patients with high-risk of distant disease based on tumor biology. 8-12,21-23 the results of this prospective study confirm that the accurate identification of risk provided by the gep test informs appropriate clinical management and patient care decisions. the results are consistent with several recent reports demonstrating the gep’s impact on management decisions as measured by changes in follow up and surveillance practices following receipt of the test result. 17-19 as seen in prior studies, the management changes reported herein show that physicians used the tumor biology information provided by the test to adjust the intensity of surveillance for low-risk class 1 and high-risk class 2, directing more frequent and intense surveillance to the latter, which helps focus healthcare resources to those patients who need it most. these results demonstrate that the gep test influences cutaneous melanoma patient management, with guideline recommended risk-appropriate changes that match the biological risk of the tumor. we report the clinical impact of a prognostic 31-gene expression profile test on clinical management decisions for 247 prospectively enrolled patients diagnosed with cutaneous melanoma at 16 u.s. centers. study results support that the gep test was a significant factor for guiding patient management, as demonstrated by changes in preand posttest care for 49% of the patients assessed. additionally, management changes were made in a risk-appropriate manner for most patients, with decreased intensity of care for class 1, low-risk patients, and increased intensity of care for high risk, class 2 patients (most often with more frequent office visits and imaging). thus, the 31gene gep test impacted clinical management decisions and led to changes in management that were aligned with guideline recommendations for the care of patients with melanoma. acknowledgements: the authors would like to thank the laboratory personnel and clinical data coordinators who provided technical and administrative support for completing this study. conflict of interest disclosures: krc, rwc, cj, and fam are employees of castle biosciences, inc. and hold stock options in the company. funding: this study was sponsored by castle biosciences, inc. the participating institutions and investigators did not receive financial compensation for their involvement. corresponding author: robert w. cook, phd 820 s. friendswood drive, suite 201 friendswood, tx 77546 832-974-1556 (office) 866-804-1556 (fax) rcook@castlebiosciences.com conclusion skin march 2018 volume 2 issue 2 copyright 2018 the national society for cutaneous medicine 119 references: 1. coit dg, thompson ja, albertini mr, et al. melanoma, version 1.2018, nccn clinical practice guidelines in oncology. 2018. 2. shaikh wr, dusza sw, weinstock ma, et al. melanoma thickness and survival trends in the united states, 1989 to 2009. j natl cancer inst. 2016 jan;108(1). 3. whiteman dc, baade pd, olsen cm. more people die from thin melanomas (1 mm) than from thick melanomas (>4 mm) in queensland, australia. j investig dermatol. 2015 apr;135(4):1190-3. 4. morton dl, thompson jf, cochran aj, et al. final trial report of sentinel-node biopsy versus nodal observation in melanoma. n engl j med. 2014 feb 13;370(7):599-609. 5. livingstone e, krajewski c, eigentler tk, et al. prospective evaluation of follow-up in melanoma patients in germany results of a multicentre and longitudinal study. eur j 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associated with cutaneous melanoma. clin cancer res. 2015 jan 1;21(1):175-83. 15. zager js, gastman, b. r., messina, j., sondak, v. k., ferris, l., cook, r. w., middlebrook, b. m., johnson, c., maetzold, d., monzon, f. a., wayne, j. d, gerami, p. . performance of a 31-gene expression profile in a previously unreported cohort of 334 cutaneous melanoma patients. j clin oncol. 2016;34(15_suppl):9581. 16. hsueh ec, debloom jr, lee j, et al. interim analysis of survival in a prospective, multi-center registry cohort of cutaneous melanoma tested with a prognostic 31-gene expression profile test. j hematol oncol. 2017 aug 29;10(1):152. doi: 10.1186/s13045-0170520-1. 17. berger ac, davidson rs, poitras jk, et al. clinical impact of a 31-gene expression profile test for cutaneous melanoma in 156 prospectively and consecutively tested patients. curr med res opin. 2016 may 23;32(9):1599-1604. 18. farberg as, glazer am, white r, et al. impact of a 31-gene expression profiling test for cutaneous melanoma on dermatologists' clinical management decisions. j drugs dermatol. 2017 may 01;16(5):428-431. 19. schuitevoerder d, heath m, cook rw, et al. impact of gene expression profiling on decision-making in clinically node negative melanoma patients after surgical staging. j drugs dermatol. 2018;in press. 20. coit dg, thompson ja, algazi a, et al. melanoma, version 2.2016, nccn clinical practice guidelines in oncology. j natl compr canc netw. 2016 apr;14(4):450-73. 21. del vecchio m, ascierto pa, mandala m, et al. vemurafenib in brafv600 mutated metastatic melanoma: a subanalysis of the italian population of a global safety study. future oncol. 2015;11(9):1355-62. 22. kaufman h at, nemunaitis jj, chesne, ja, delman ka, spitler le, collichio fa, ross mi, zhang y, shilkrut m, andtbacka rhi. tumor size and clinical outcomes in melanoma patients (mel pts) treated with talimogene laherparepvec (t-vec). j clin oncol. 2015;33(15_suppl):9074. skin march 2018 volume 2 issue 2 copyright 2018 the national society for cutaneous medicine 121 23. steinman j, ariyan c, rafferty b, et al. factors associated with response, survival, and limb salvage in patients undergoing isolated limb infusion. j surg oncol. 2014 apr;109(5):405-9. synopsis conclusions bimekizumab was well-tolerated across the plaque psoriasis clinical program; most teaes were mild to moderate and discontinuations were low. all candida infections were mucocutaneous in origin, with oral candidiasis being most frequent; oral candidiasis teaes were predominantly mild to moderate and the vast majority did not lead to discontinuation. objective to report shortand longer-term safety data in bimekizumab-treated patients with moderate to severe plaque psoriasis pooled from eight phase 2/3 trials. background • bimekizumab is a monoclonal igg1 antibody that selectively inhibits interleukin (il)-17f in addition to il-17a.1,2 • given that psoriasis is a chronic disease requiring long-term management, it is important to understand the long-term safety profiles of therapies such as bimekizumab. • we report shortand longer-term safety data in bimekizumab-treated patients with moderate to severe plaque psoriasis, and short-term data from adalimumab, ustekinumab, and placebo phase 3 comparator arms. methods • patients were included from four phase 3 trials – be sure, be vivid, be ready, and the be bright open-label extension (interim cut: november 1, 2019) – and four phase 2 studies – be able 1, be able 2, ps0016, and ps0018. patients received bimekizumab 320 mg every 4 or 8 weeks (q4w/q8w; additional doses used in phase 2), adalimumab, ustekinumab, or placebo. • short-term safety from the initial treatment periods (weeks 0–16) of three of the phase 3 trials (be sure, be vivid, and be ready) was evaluated for patients who received ≥1 dose of bimekizumab, adalimumab, ustekinumab, or placebo. • longer-term safety was also evaluated for patients who received ≥1 dose of bimekizumab in be sure, be vivid, be ready, be bright, and the four phase 2 trials. • we report treatment emergent adverse events (teaes; n [%]) for the initial treatment period for patients receiving bimekizumab 320 mg q4w, adalimumab, ustekinumab, and placebo, as well as longer-term teaes for patients receiving bimekizumab 320 mg q4w and all other doses of bimekizumab. – exposure-adjusted incidence rates (eairs) are the incidence of new cases per 100 patient-years (py) in patients receiving bimekizumab 320 mg q4w (short-term) and all patients receiving any dose of bimekizumab (longer-term). – teaes were coded using meddra v19.0. results patient population • over 16 weeks, 989 patients with psoriasis received ≥1 bimekizumab dose, 159 patients received adalimumab, 163 patients received ustekinumab, and 169 patients received placebo. • patient demographics and baseline disease characteristics are reported in table 1. short-term safety outcomes • 593 (60.0%) bimekizumab-treated patients experienced ≥1 teae, versus 96 (60.4%) adalimumab-treated patients, 83 (50.9%) ustekinumab-treated patients, and 74 (43.8%) placebo-treated patients (table 2). • serious teaes occurred in <4% of patients in each treatment group, ranging from 1.5% for bimekizumab to 3.1% for ustekinumab. • discontinuations due to teaes occurred in <5% of patients in each group, ranging from 1.7% for bimekizumab to 4.1% for placebo (table 2). longer-term safety outcomes • over the longer term, teaes in bimekizumab-treated patients occurred at a rate of 238.0/100 py, serious teaes at 6.6/100 py, and discontinuations due to teaes at 4.9/100 py (table 2). • serious infections occurred at a rate of 1.4/100 py in bimekizumab-treated patients; rates of malignancies and adjudicated major adverse cardiac events were lower, occurring at 0.8/100 py and 0.7/100 py, respectively (table 3). • there was one active suicidal ideation in a bimekizumab-treated patient with pre-existing psychological conditions and one case of inflammatory bowel disease in a bimekizumab-treated patient (table 3). • 17.0% of bimekizumab-treated patients experienced mucocutaneous candida infection teaes, out of which 15.1% were oral candidiasis (table 4). – 1 serious case (<0.1%) and 6 candidiasis-related discontinuations (0.3%) occurred. k. reich,1 a. blauvelt,2 m. lebwohl,3 k.a. papp,4 p. rich,5 b. strober,6,7 d. de cuyper,8 c. madden,9 l. peterson,9 v. vanvoorden,8 r.b. warren10 ada: adalimumab; bkz: bimekizumab; bsa: body surface area; ci: confidence interval; dlqi: dermatology life quality index; eair: exposure-adjusted incidence rate; iga: investigator’s global assessment; il: interleukin; mace: major adverse cardiovascular event; nmsc: non-melanoma skin cancers; pasi: psoriasis area and severity index; pbo: placebo; py: patient-years; q2/4/8/12w: every 2/4/8/12 weeks; sd: standard deviation; sib: suicidal ideation and behavior; teae: treatment emergent adverse event; tnf: tumor necrosis factor; ust: ustekinumab. longer-term all bkz (n=1789) eair per 100 py (95% ci) n (%) serious | n (%) severe | n (%) candida infections 18.7 (16.7, 21.0) 304 (17.0) 1 (<0.1) 4 (0.2) oral candidiasis 16.4 (14.5, 18.5) 271 (15.1) 0 3 (0.2) oropharyngeal candidiasis 1.2 (0.7, 1.8) 21 (1.2) 0 0 skin candidiasis 0.6 (0.3, 1.1) 11 (0.6) 0 0 vulvovaginal candidiasis 0.8 (0.5, 1.4) 15 (0.8) 0 0 esophageal candidiasis 0.3 (0.1, 0.6) 5 (0.3) 1 (<0.1) 1 (<0.1) leading to discontinuation 0.3 (0.1, 0.7) 6 (0.3) 1 (<0.1) 1 (<0.1) institutions: 1center for translational research in inflammatory skin diseases, institute for health services research in dermatology and nursing, university medical center hamburg-eppendorf and skinflammation® center, hamburg, germany; 2oregon medical research center, portland, oregon, usa; 3icahn school of medicine at mount sinai, new york, new york, usa; 4probity medical research and k papp clinical research, waterloo, ontario, canada; 5oregon dermatology and research center, portland, oregon, usa; 6yale university, new haven, connecticut, usa; 7central connecticut dermatology research, cromwell, connecticut, usa; 8ucb pharma, brussels, belgium; 9ucb pharma, raleigh, north carolina, usa; 10dermatology centre, salford royal nhs foundation trust, manchester nihr biomedical research centre, the university of manchester, manchester, uk bimekizumab safety in patients with moderate to severe psoriasis: analysis of pooled data from phase 2 and 3 clinical trials presented at winter clinical 2021 virtual congress | january 16–24 references: 1glatt s. br j clin pharmacol 2017;83:991–1001; 2papp ka. j am acad dermatol 2018;79:277–86 e10. author contributions: substantial contributions to study conception/design, or acquisition/analysis/interpretation of data: kr, ab,ml, kap, pr, bs, ddc, cm, lp, vv, rbw; drafting of the publication, or revising it critically for important intellectual content: kr, ab,ml, kap, pr, bs, ddc, cm, lp, vv, rbw; final approval of the publication: kr, ab,ml, kap, pr, bs, ddc, cm, lp, vv, rbw. author disclosures: kr: served as advisor and/or paid speaker for and/or participated in clinical trials sponsored by abbvie, affibody, almirall, amgen, avillion, biogen, boehringer ingelheim, bristol myers squibb, celgene, centocor, covagen, dermira, eli lilly, forward pharma, fresenius medical care, galapagos, gsk, janssen, kyowa kirin, leo pharma, medac, msd, miltenyi biotec, novartis, ocean pharma, pfizer, regeneron, samsung bioepis, sanofi, sun pharma, takeda, ucb pharma, valeant/bausch health, and xenoport; ab: served as a scientific adviser and/or clinical study investigator for abbvie, allergan, almirall, athenex, boehringer ingelheim, bristol myers squibb, dermavant, eli lilly, forte, galderma, incyte, janssen, leo pharma, novartis, pfizer, rapt, regeneron, sanofi genzyme, sun pharma, and ucb pharma; paid speaker for abbvie; ml: employee of mount sinai which receives research funds from abbvie, amgen, arcutis, boehringer ingelheim, dermavant, eli lilly, incyte, janssen, leo pharma, ortho dermatologics, pfizer, and ucb pharma; consultant for aditum bio, allergan, almirall, arcutis, avotres, birchbiomed, bmd skincare, boehringer ingelheim, bristol myers squibb, cara therapeutics, castle biosciences, corrona, dermavant, evelo, facilitate international dermatologic education, foundation for research and education in dermatology, inozyme pharma, leo pharma, meiji seika pharma, menlo, mitsubishi pharma, neuroderm, pfizer, promius/dr. reddy’s laboratories, serono, theravance, and verrica; kap: honoraria and/or grants from abbvie, akros, amgen, arcutis, astellas, baxalta, boehringer ingelheim, bristol myers squibb, canfite, celgene, coherus, dermira, dow pharma, eli lilly, forward pharma, galderma, genentech, gilead, gsk, janssen, kyowa kirin, leo pharma, medimmune, merck (msd), merck-serono, mitsubishi pharma, moberg pharma, novartis, pfizer, prcl research, regeneron, roche, sanofi genzyme, sun pharma, takeda, ucb pharma, and valeant/bausch health; consultant (no compensation) for astrazeneca and meiji seika pharma; pr: research grants due to being principal investigator from abbvie, arcutis, bristol myers squibb, centocor, dermavant, eli lilly, kadmon, merck, novartis, pfizer, sun pharma, and ucb pharma; bs: consultant (honoraria) from abbvie, almirall, amgen, arcutis, arena, aristea, boehringer ingelheim, bristol myers squibb, celgene, dermavant, dermira, eli lilly, equillium, gsk, janssen, leo pharma, meiji seika pharma, mindera, novartis, ortho dermatologics, pfizer, regeneron, sanofi genzyme, sun pharma, and ucb pharma; speaker for abbvie, amgen, eli lilly, janssen, and ortho dermatologics; scientific director (consulting fee) for corrona psoriasis registry; investigator for abbvie, cara therapeutics, corrona psoriasis registry, dermavant, dermira, and novartis; editor-in-chief (honorarium) for journal of psoriasis and psoriatic arthritis; ddc, lp, vv: employees of ucb pharma; cm: employee and shareholder of ucb pharma; rbw: consulting fees from abbvie, almirall, amgen, arena, avillion, boehringer ingelheim, bristol myers squibb, celgene, eli lilly, janssen, leo pharma, novartis, pfizer, sanofi, and ucb pharma; research grants from abbvie, almirall, amgen, celgene, eli lilly, janssen, leo pharma, novartis, pfizer, and ucb pharma. acknowledgements: this study was funded by ucb pharma. we thank the patients and their caregivers in addition to the investigators and their teams who contributed to this study. the authors acknowledge mylene serna, pharmd, ucb pharma, smyrna, ga, usa and susanne wiegratz, msc, ucb pharma, monheim am rhein, germany for publication coordination; eva cullen, phd, ucb pharma, brussels, belgium for critical review; daniel smith, ba, costello medical, cambridge, uk for medical writing and editorial assistance; and the costello medical design team for design support. all costs associated with development of this poster were funded by ucb pharma. previously presented at eadv 2020 virtual congress | october 29–31 abkz initial treatment period (weeks 0–16) data are included from three pivotal phase 3 studies, be sure (nct03412747), be vivid (nct03370133), and be ready (nct03410992); bada initial treatment period data are from one pivotal phase 3 study, be sure; cust initial treatment period data are from one pivotal phase 3 study, be vivid; dpbo initial treatment period data are from two pivotal phase 3 studies, be vivid and be ready; ebkz longer-term data are pooled from four phase 3 trials (be sure, be vivid, be ready, be bright [nct03598790]) and four phase 2 trials (be able 1, be able 2, ps0016, and ps0018). fin the bkz, ust, and pbo short-term groups, one patient with mild iga score was mistakenly enrolled. table 2 occurrence of shortand longer-term teaes short-term safety was evaluated for patients receiving bimekizumab 320 mg q4w compared with adalimumab, ustekinumab, and placebo in three phase 3 trials. longer-term safety was evaluated for patients receiving any dose of bimekizumab across eight phase 2/3 trials. initial treatment period (week 0–16) short-term longer-term n (%) eair/100 py (95% ci) bkz 320 mg q4w (n=989) ada (n=159) ust (n=163) pbo (n=169) bkz 320 mg q4w (n=989) all bkz (n=1789) any teae 593 (60.0) 96 (60.4) 83 (50.9) 74 (43.8) 315.7 (290.8, 342.1) 238.0 (226.0, 250.5) serious teaes 15 (1.5) 3 (1.9) 5 (3.1) 4 (2.4) 4.9 (2.8, 8.1) 6.6 (5.5, 7.9) discontinuation due to teaes 17 (1.7) 4 (2.5) 3 (1.8) 7 (4.1) 5.6 (3.3, 8.9) 4.9 (4.0, 6.1) drug-related teaes 212 (21.4) 32 (20.1) 19 (11.7) 15 (8.9) 79.5 (69.2, 90.9) 47.3 (43.7, 51.1) severe teaes 12 (1.2) 4 (2.5) 3 (1.8) 4 (2.4) 3.9 (2.0, 6.9) 6.4 (5.2, 7.6) deaths 1 (0.1) 1 (0.6) 1 (0.6) 1 (0.6) 0.3 (0.0, 1.8) 0.3 (0.1, 0.6) aincludes one event adjudicated by the external neuropsychiatric committee (active suicidal ideation with some intent to act) in a patient with pre-existing psychiatric conditions; bincludes one fatal event of circulatory failure (adjudicated mace), one event of atopic dermatitis-like disseminated eczema, and one case of anaphylactic shock due to insect sting, all considered unrelated to study treatment. table 1 patient demographics and baseline disease characteristics initial treatment period (week 0–16) longer-term bkz 320 mg q4wa (n=989) adab (n=159) ustc (n=163) pbod (n=169) all bkze (n=1789) age (years), mean ± sd 44.8 ± 13.4 45.5 ± 14.3 46.0 ± 13.6 46.6 ± 13.7 45.2 ± 13.5 male, n (%) 698 (70.6) 114 (71.7) 117 (71.8) 118 (69.8) 1252 (70.0) caucasian, n (%) 841 (85.0) 141 (88.7) 120 (73.6) 142 (84.0) 1468 (82.1) weight (kg), mean ± sd 89.6 ± 22.2 90.5 ± 22.1 87.2 ± 21.1 90.4 ± 24.3 89.0 ± 22.0 duration of plaque psoriasis (years), mean ± sd 18.2 ± 12.5 16.2 ± 11.9 17.8 ± 11.6 19.4 ± 13.2 17.7 ± 12.3 pasi, mean ± sd 20.9 ± 7.6 19.1 ± 5.9 21.3 ± 8.3 20.1 ± 7.2 20.6 ± 7.8 bsa (%), mean ± sd 26.4 ± 15.6 25.0 ± 14.4 27.3 ± 16.7 25.7 ± 16.2 26.7 ± 16.3 iga, n (%)f 3: moderate 656 (66.3) 114 (71.7) 96 (58.9) 116 (68.6) 1217 (68.0) 4: severe 332 (33.6) 45 (28.3) 66 (40.5) 52 (30.8) 567 (31.7) dlqi total, mean ± sd 10.4 ± 6.3 10.5 ± 7.4 11.0 ± 6.9 10.7 ± 6.8 10.3 ± 6.6 prior biologic therapy, n (%) 380 (38.4) 53 (33.3) 63 (38.7) 70 (41.4) 636 (35.6) anti-tnf 132 (13.3) 14 (8.8) 24 (14.7) 26 (15.4) 234 (13.1) anti-il-17 231 (23.4) 35 (22.0) 38 (23.3) 36 (21.3) 341 (19.1) initial treatment period (week 0–16) short-term longer-term n (%) eair/100 py (95% ci) bkz 320 mg q4w (n=989) ada (n=159) ust (n=163) pbo (n=169) bkz 320 mg q4w (n=989) all bkz (n=1789) serious infections 3 (0.3) 0 2 (1.2) 0 1.0 (0.2, 2.9) 1.4 (0.9, 2.0) inflammatory bowel disease 1 (0.1) 0 0 0 0.3 (0.0, 1.8) 0.1 (0.0, 0.3) candida infections 90 (9.1) 0 0 0 30.6 (24.6, 37.6) 18.7 (16.7, 21.0) oral candidiasis 75 (7.6) 0 0 0 25.3 (19.9, 31.8) 16.4 (14.5, 18.5) adjudicated mace 1 (0.1) 0 0 0 0.3 (0.0, 1.8) 0.7 (0.3, 1.1) malignancies (inc. nmsc) 4 (0.4) 1 (0.6) 0 1 (0.6) 1.3 (0.4, 3.4) 0.8 (0.5, 1.4) adjudicated sib 0 0 0 0 0 0.1 (0.0, 0.3)a serious hypersensitivity reactions 0 0 0 0 0 0.2 (0.0, 0.5)b injection site reactions 27 (2.7) 3 (1.9) 2 (1.2) 2 (1.2) 9.0 (5.9, 13.1) 3.1 (2.4, 4.1) hepatic events 19 (1.9) 9 (5.7) 0 2 (1.2) 6.3 (3.8, 9.8) 5.6 (4.6, 6.8) liver function analyses 18 (1.8) 9 (5.7) 0 2 (1.2) 5.9 (3.5, 9.4) 4.8 (3.8, 5.9) table 3 occurrence of shortand longer-term teaes of interest table 4 longer-term candida infections in bkz-treated patients bimekizumab was well-tolerated; the majority of teaes were mild to moderate in severity and discontinuations were low. oral candidiasis was the most frequent candida infection; the vast majority of oral candidiasis teaes were mild to moderate and did not lead to discontinuation. population exposure dosing trials administered short-term (be sure, be vivid, and be ready) week 0–16 bkz n=989 306.4 py 320 mg q4w 3 double-blinded trials ada n=159 48.8 py 80 mg loading dose, followed by 40 mg q2w from week 1 1 double-blinded trial ust n=163 50.1 py 45/90 mg (by weight) q12w, after q4w to week 4 1 double-blinded trial pbo n=169 51.6 py placebo 2 double-blinded trials longer term (phase 2/3) data cut-off: november 1, 2019 bkz all doses n=1789 1830.4 py (range: 1–670 days) 320 mg q4w, 320 mg q8w, 64 mg q4w (phase 2), 160 mg q4w (phase 2), 480 mg q4w (phase 2) 6 double-blinded trials 2 open-label extension studies short-term safety outcomes 5.0% teae-related discontinuations serious teaes 5.0% 5.0% 5.0% short-term longer-term serious infections e xp o su re -a d ju st e d in c id e n c e r a te ( p e r 10 0 p y ) 40.0 30.0 20.0 10.0 0.0 1.5% 1.7% 1.9% 2.5% 3.1% 1.8% 2.4% 4.1% 1.0 25.3 30.6 1.4 16.4 18.7 o ra l c a n d id ia si s c a n d id a in fe c ti o n s o ra l c a n d id ia si s c a n d id a in fe c ti o n s 40.0 30.0 20.0 10.0 0.0 shortand longer-term safety for bimekizumab presented at winter clinical dermatology conference 2018 | hawaii | 12–17 jan 2018 safety of certolizumab pegol in chronic plaque psoriasis: cumulative data over 48 weeks’ exposure from phase 3, multicenter, randomized, placebo-controlled studies a. blauvelt,1 b. strober,2,3 r. langley,4 d. burge,5 l. pisenti,6 m. yassine,6 s. kavanagh,7 c. arendt,8 r. rolleri,7 k. reich9 1oregon medical research center, portland, or; 2university of connecticut health center, farmington, ct; 3probity medical research, waterloo, ontario, canada; 4dalhousie university, nova scotia, canada; 5dermira inc, menlo park, ca; 6ucb pharma, atlanta, ga; 7ucb pharma, raleigh, nc; 8ucb pharma, brussels, belgium; 9dermatologikum hamburg and sciderm research institute, hamburg, germany references: 1. rachakonda td. et al. j am acad dermatol 2014;70(3):512–516; 2. kurd sk. et al. j am acad dermatol 2009;60(2):218–224; 3. danielsen k. et al. br j dermatol 2013; 168(6):1303–1310; 4. reich k. et al. br j dermatol 2012; 167(1):180–190; 5. gottlieb ab. et al. aad 2017 abstract; 6. augustin m. et al. skin 2017;1:s24; 7. reich k. et al. skin 2017;1:s23. author contributions: substantial contributions to study conception/design, or acquisition/analysis/interpretation of data: ab, bs, rl, db, lp, my, sk, ca, rr, kr; drafting of the publication, or revising it critically for important intellectual content: ab, bs, rl, db, lp, my, sk, ca, rr, kr; final approval of the publication ab, bs, rl, db, lp, my, sk, ca, rr, kr. author disclosures: ab: consulting honoraria, clinical investigator and/or speaker’s fees: abbvie, aclaris, almirall, amgen, boehringer ingelheim, celgene, dermavant, dermira, inc., eli lilly, genentech/roche, glaxosmithkline, janssen, leo pharma, merck, novartis, pfizer, purdue pharma, regeneron, sandoz, sanofi genzyme, sienna pharmaceuticals, sun pharma, ucb pharma, valeant, vidac; bs: consulting fees and/or other honraria: abbvie, almirall, amgen, astra zeneca, boehringer ingelheim, celgene, dermira, inc., eli lilly, glaxosmithkline, janssen, leo pharma, medac, novartis, pfizer, sun pharma, ucb pharma, ortho dermatologics/valeant, regeneron, sanofi-genzyme; corrona psoriasis registry; grant support to the university of connecticut for fellowship program (payments to the university of connecticut, not bs): abbvie, janssen; rl: honoraria: abbvie, amgen, centocor, pfizer, janssen pharmaceuticals, leo pharma, boehringer ingelheim international gmbh, eli lilly, valeant pharmaceuticals; db: employee of dermira, inc.; lp, my, sk, ca, rr: employees of ucb pharma; kr: consulting and/or other fees: abbvie, amgen, biogen, boehringer ingelheim pharma, celgene, covagen, forward pharma, glaxosmithkline, janssen-cilag, leo pharma, eli lilly, medac, merck sharp & dohme corp, novartis, pfizer, regeneration, takeda, ucb pharma, xenoport. acknowledgements: the studies were funded by dermira, inc. in collaboration with ucb. ucb is the regulatory sponsor of certolizumab pegol in psoriasis. medical writing support for this presentation was provided by costello medical. all costs associated with the development of this presentation were funded by ucb. objective • to assess cumulative 48-week safety data from all phase 3 trials in the clinical development program of certolizumab pegol for the treatment of moderate-to-severe chronic plaque psoriasis. synopsis • plaque psoriasis (pso) is a chronic, immune-mediated, inflammatory disease affecting ~3% of adults in the us,1,2 and ~2–6% in europe.3 • certolizumab pegol (czp), the only fc-free, pegylated, anti-tumor necrosis factor (tnf) biologic, is approved for the treatment of adults with rheumatoid arthritis, psoriatic arthritis, crohn’s disease (us), ankylosing spondylitis and non-radiographic axial spondyloarthritis (eu). • czp has demonstrated promising results in the treatment of adults with moderate-to-severe pso in phase 24 and phase 3 trials, where clinical and patient reported improvements were shown over 16 weeks of treatment and maintained through 48 weeks.5,6,7 methods patients • data were pooled from three ongoing phase 3 trials of czp in adults with pso: cimpasi-1 [nct02326298], cimpasi-2 [nct02326272], and cimpact [nct02346240]. • the trials enrolled adults with pso ≥6 months with psoriasis area severity index [pasi] ≥12, ≥10% body surface area [bsa] affected, and physician’s global assessment [pga] ≥3 on a 5-point scale. • for the initial period (weeks 0–16), patients were randomized to subcutaneous czp 400 mg every two weeks (q2w), 200 mg q2w (following 400 mg loading dose at weeks 0, 2 and 4), placebo q2w, or etanercept (etn) 50 mg twice weekly (biw) for 12 weeks in cimpact (figure 1). • at week 16, patients entered the double-blind maintenance period (weeks 16–48). in cimpasi-1 and cimpasi-2 those classed as responders (pasi 50) continued at the same dose. in cimpact, responders (pasi 75) were re-randomized to czp or placebo (figure 1). safety assessments • 48-week safety data were pooled across studies for patients receiving ≥1 dose of czp during the initial and/or maintenance periods of the studies, with up to 48 weeks of exposure as of the cut off dates 20 october 2016 (cimpasi-1), 16 august 2016 (cimpasi-2), 5 december 2016 (cimpact). • 16-week safety data were pooled across studies for patients receiving ≥1 dose of czp during the initial period of the studies. • adverse events (aes) and serious adverse events (saes) were classified according to the medical dictionary for regularity activities (meddra) v.18.1. • an sae was defined as an ae meeting one or more of the following criteria: death, life-threatening, significant or persistent disability/incapacity, congenital anomaly/birth defect, important medical event, initial or prolonged inpatient hospitalization. • incidence rates (ir) were calculated as incidence of new cases per 100 patient-years (py). results patient population • across all three studies, a total of 962 patients received ≥1 dose czp during weeks 0–48: 460 received czp 200 mg q2w and 627 received 400 mg czp q2w. • baseline demographics are shown in table 1. incidence of adverse events and serious adverse events • over 48 weeks of czp treatment, 709 patients (73.7%) experienced ≥1 ae (table 2). – all czp (n=962), ir=219.6 (95% confidence interval [ci]=203.7–236.4) – czp 200 mg q2w (n=460), ir=221.2 (95% ci=197.6, 246.7) – czp 400 mg q2w (n=627), ir=228.6 (95% ci= 207.8, 250.9) • ir of aes did not increase with longer exposure duration. in patients with up to 16 weeks of exposure, ae irs were: – all czp (n=692), ir=319.1 (95% ci=289.1–351.4) – czp 200 mg q2w (n=350), ir=292.1 (95% ci=252.8–335.9) – czp 400 mg q2w (n=342), ir=348.3 (95% ci=303.5–397.9) – placebo (n=157), ir=342.6 (95% ci=277.8, 417.9) conclusions • across all available safety data for patients treated with czp for up to 48 weeks in phase 3 clinical trials of pso, the safety profile was as expected for this therapeutic class. • number and type of aes and saes reported was similar between czp 400 mg q2w and 200 mg q2w treatment groups, and overall ir for aes did not increase with treatment duration. • these studies show that czp, an anti-tnf biologic, affords a novel treatment option for psoriasis patients. all czp (n=962) czp 200 mg q2w (n=460) czp 400 mg q2w (n=627) ir/100 py (95% ci) n (%) ir/100 py (95% ci) n (%) ir/100 py (95% ci) n (%) total aes 219.6 (203.7, 236.4) 709 (73.7) 221.2 (197.6, 246.7) 321 (69.8) 228.6 (207.8, 250.9) 444 (70.8) severe 7.5 (5.6, 9.8) 53 (5.5) 6.2 (3.8, 9.7) 19 (4.1) 8.3 (5.8, 11.6) 34 (5.4) drug-related 29.6 (25.5, 34.1) 187 (19.4) 28.5 (22.6, 35.6) 78 (17.0) 31.4 (25.9, 37.7) 115 (18.3) aes leading to withdrawal 5.0 (3.5, 6.9) 36 (3.7) 3.9 (2.0, 6.8) 12 (2.6) 5.8 (3.7, 8.6) 24 (3.8) total saes 9.1 (7.0, 11.6) 64 (6.7) 7.6 (4.8, 11.4) 23 (5.0) 10.1 (7.3, 13.8) 41 (6.5) aes leading to death 0.1 (0.0, 0.8) 1 (0.1) 0 0 0.2 (0.0, 1.3) 1 (0.2) patients who received both czp 200 mg q2w and czp 400 mg q2w are included in the population count for the ‘all czp’ group. total exposure for all czp patients from baseline to week 48=730 py. agastroenteritis, pancreas infection and pneumonia. bescherichia coli sepsis and pyelonephritis in the same patient; abdominal abscess and haematoma in the same patient related to a bicycle accident; endophthalmitis, pneumonia, sepsis, tuberculosis, each in 1 patient; erysipelas in 2 patients. cprimary progressive multiple sclerosis was an incidental finding during evaluation for low back pain (no aes during study) and considered unrelated to treatment by the investigator. danaplastic oligodendroglioma. etwo cases of basal cell carcinoma and 1 keratoacanthoma. figure 1. study design for cimpasi-1, cimpasi-2 and cimpact phase 3 trials ain cimpasi-1/-2, pasi 50 non-responders at week 16 entered the escape arm for treatment with open label czp 400 mg q2w; bupon entering the maintenance period, placebo-treated pasi 75 responders (≥75% reduction in pasi) continued blinded placebo treatment and placebo-treated pasi 50–74 responders (≥50% but <75% reduction in pasi) received czp 400 mg loading dose at weeks 16, 18 and 20 then czp 200 mg q2w; cin cimpact, pasi 75 non-responders at week 16 entered the escape arm for treatment with open label czp 400 mg q2w. etn: etanercept; ld: loading dose; pasi: psoriasis area and severity index; pga: physician global assessment. cimpasi-1 & cimpasi-2 cimpact 2:2:1 randomization cimpasi-1 | cimpasi-2 n=234 | 227 3:3:3:1 randomization n=559 week 0 16a,b 48 144 week 0 16c 48 144 double-blind maintenance period • • long-term therapy czp-treated responders (pasi 50) continued on the same dose double-blind maintenance period • • long-term therapy czpand etn-treated responders (pasi 75) re-randomized to czp or placebo open-label treatment open-label treatment co-primary endpoints at week 16 pasi 75 and pga 0/1 primary endpoint at week 12 pasi 75 ld czp 200 mg q2w (n=95 | 91) czp 400 mg q2w (n=88 | 87) placebo q2w (n=51 | 49) ld czp 200 mg q2w (n=165) czp 400 mg q2w (n=167) placebo q2w (n=57) etn 50 mg biw (n=170) 12 washout table 1. pooled demographics and baseline characteristics for patients exposed to czp during weeks 0–48 across cimpasi-1, cimpasi-2 and cimpact all czp (n=962) czp 200 mg q2w (n=460) czp 400 mg q2w (n=627) patient characteristics age, years, mean (sd) 45.6 (13.1) 45.6 (13.2) 45.4 (12.9) male, n (%) 633 (65.8) 312 (67.8) 403 (64.3) caucasian, n (%) 906 (94.2) 438 (95.2) 587 (93.6) bmi, mean (sd) 30.4 (7.1) 30.5 (6.8) 30.4 (7.1) disease duration, years, mean (sd) 18.3 (12.4) 18.6 (12.8) 17.9 (12.0) prior treatment, n (%) biologic therapy 0 674 (70.1) 322 (70.0) 443 (70.7) 1 220 (22.9) 105 (22.8) 139 (22.2) 2 67 (7.0) 33 (7.2) 44 (7.0) ≥3 1 (0.1) 0 1 (0.2) anti-tnf 119 (12.4) 57 (12.4) 71 (11.3) anti-il-17 142 (14.8) 78 (17.0) 89 (14.2) anti-il-12/il-23 47 (4.9) 15 (3.3) 39 (6.2) patients who received both czp 200 mg q2w and czp 400 mg q2w are included in the population count for the all czp group. bmi: body mass index; il: interleukin; sd: standard deviation. table 2. overview of aes and saes during weeks 0–48 across cimpasi-1, cimpasi-2 and cimpact • over 48 weeks of czp treatment, ir was similar across both the czp 200 mg q2w and czp 400 mg q2w dose groups (table 2). • 64 czp-treated patients (6.7%) reported saes across the 48 weeks (table 2). • 1 death occurred during the 48-week period due to a motor vehicle accident (table 2). adverse events of interest • selected saes are shown in table 4. • the rate of serious infections was low (table 4), comparable with other anti-tnfs in this indication. – there was 1 case of active tuberculosis (tb) in a patient who received etn during the initial 16week period before switching to czp 400 mg q2w (table 4). tb was diagnosed 172 days after etn initiation, 60 days after czp initiation. the patient discontinued the study. – no other opportunistic infections were reported. all czp (n=962) czp 200 mg q2w (n=460) czp 400 mg q2w (n=627) ir/100 py (95% ci) n (%) ir/100 py (95% ci) n (%) ir/100 py (95% ci) n (%) nasopharyngitis 28.5 (24.5, 33.0) 181 (18.8) 29.3 (23.2, 36.4) 80 (17.4) 29.7 (24.3, 35.8) 109 (17.4) upper repiratory tract infection 13.3 (10.7, 16.3) 91 (9.5) 13.4 (9.5, 18.3) 39 (8.5) 13.9 (10.5, 18.2) 55 (8.8) hypertension 6.5 (4.8, 8.7) 46 (4.8) 6.0 (3.6, 9.5) 18 (3.9) 6.9 (4.6, 10.0) 28 (4.5) headache 6.1 (4.4, 8.2) 43 (4.5) 6.0 (3.5, 9.4) 18 (3.9) 6.4 (4.2, 9.4) 26 (4.1) arthralgia 5.1 (3.5, 7.0) 36 (3.7) 6.3 (3.8, 9.8) 19 (4.1) 4.2 (2.4, 6.6) 17 (2.7) table 3. most commonly reported aes (≥3% patients) during weeks 0–48 across cimpasi-1, cimpasi-2 and cimpact all czp (n=962) czp 200 mg q2w (n=460) czp 400 mg q2w (n=627) ir/100 py (95% ci) n (%) ir/100 py (95% ci) n (%) ir/100 py (95% ci) n (%) serious infections 1.5 (0.8, 2.7) 11 (1.1) 1.0 (0.2, 2.8) 3 (0.7)a 1.9 (0.8, 3.8) 8 (1.3)b active tuberculosis 0.1 (0.0, 0.8) 1 (0.1) 0 0 0.2 (0.0, 1.3) 1 (0.2) primary progressive multiple sclerosis 0.1 (0.0, 0.8) 1 (0.1) 0 0 0.2 (0.0, 1.3) 1 (0.2)c congestive heart failure 0.1 (0.0, 0.8) 1 (0.1) 0 0 0.2 (0.0, 1.3) 1 (0.2) malignancies (excluding nonmelanoma skin cancer) 0.1 (0.0, 0.8) 1 (0.1) 0 0 0.2 (0.0, 1.3) 1 (0.2)d non-melanoma skin cancer 0.4 (0.1, 1.2) 3 (0.3) 0 0 0.7 (0.2, 2.1) 3 (0.5)e table 4. selected aes and saes of interest during weeks 0–48 across cimpasi-1, cimpasi-2 and cimpact patients who received both czp 200 mg q2w and czp 400 mg q2w are included in the population count for the ‘all czp’ group. total exposure for all czp patients from baseline to week 48=730 py. patients who received both czp 200 mg q2w and czp 400 mg q2w are included in the population count for the ‘all czp’ group. total exposure for all czp patients from baseline to week 48=730 py. • there were no reports of serious skin disorders such as steven johnson or lupus. • overall, 9 patients experienced fungal infections (high level term), ir=1.2 (95% ci=0.6, 2.4), including 1 case of fungal skin infection and 1 case of oral fungal infection, both in patients receiving czp 400 mg q2w. • there were 3 reports of oral candidiasis, 1 in a patient receiving czp 200 mg q2w, ir=0.3 (95% ci=0.0, 1.8) and 2 reports in patients receiving czp 400 mg q2w, ir=0.5 (95% ci=0.1, 1.7). there was 1 case of skin candida in a patient receiving czp 400 mg q2w, ir=0.2 (95% ci=0.0, 1.3). • malignancies were reported in 4 patients receiving czp 400 mg q2w (table 4), including 1 case of anaplastic oligodendroglioma, 2 cases of basal cell carcinoma and 1 case of keratoacanthoma. powerpoint presentation psoriasis patients on chronic biologic therapy may benefit from additional treatment—study design and baseline characteristics jerry bagel, md; james zapata; elise nelson, lpn, ccrc; and brian keegan, md, phd psoriasis treatment center of central new jersey, east windsor, new jersey background  more than 50% of patients with psoriasis are dissatisfied with their treatment, including biologic treatment1  greater disease clearance is desired by patients and is supported by the recent treat-totarget recommendations from the medical board of the national psoriasis foundation1  accordingly, patients receiving biologic therapy for psoriasis may benefit from adjunctive therapy with topical agents2,3  treatment with the foam formulation of calcipotriene 0.005%/betamethasone dipropionate 0.064% (cal/bd) as a fixed combination topical product is significantly more effective than calcipotriene or betamethasone monotherapy, and is superior to ointment and gel formulations of cal/bd4-6  patients with psoriasis who have been treated with biologic therapy for at least 24 weeks are currently being enrolled in a real-world study designed to assess the efficacy and safety of cal/bd foam as adjunctive therapy  described here is the design for this study, as well as the residual disease activity observed in these patients at enrollment poster presented at the 2018 winter clinical dermatology conference in maui, hi; january 12-17, 2018. references 1. armstrong aw, bagel j, van voorhees as, et al. jama dermatol. 2015;151(4):432-438. 2. menter a, korman nj, elmets ca, et al. j am acad dermatol. 2009;60(4):643-659. 3. bagel j, stein gold l. j drugs dermatol. 2017;16:1209-1222. 4. lebwohl m, tyring s, bukhalo m, et al. j clin aesthet dermatol. 2016;9(2):34-41. 5. paul c, stein gold l, cambazard f, et al. j eur acad dermatol venereol. 2017;31(1):119-126. 6. leonardi c, bagel j, yamauchi p, et al. j drugs dermatol. 2015;14(12):1468-1477. methods  25 adults with psoriasis (body surface area [bsa] ≤5%) being treated with biologic agents for ≥24 weeks have been enrolled in an open-label, single-arm, observational study (figure 1)  in addition to their biologic therapy, all patients will receive cal/bd foam qd for 4 weeks, followed by cal/bd foam on 2 consecutive days weekly for an additional 12 weeks  the end points will be assessed at baseline, week 4, and week 16  safety evaluations include assessments of local skin reactions and adverse events (aes) qd on 2 consecutive days per weekqd baseline 4 8 16 weeks population and key inclusion criteria • n=25 • adults with chronic plaque psoriasis • ≥24 weeks biologic therapy • bsa ≤5% prescribed biologic therapy regimen plus cal/bd foam (0.005%/0.064%) assessments 12 figure 1. study design end points physician’s global assessment (pga), bsa, pga x bsa, dermatology life quality index (dlqi), and the treatment satisfaction questionnaire for medication (tsqm)-9 demographics  18 men and 7 women; mean age, 53 years (table 1)  most of the patients are caucasian (84%), with the remaining patients being hispanic (16%)  on average, patients have had a 24-year history of psoriasis patients (n=25) age, years 53 (11) sex female male 7 (28%) 18 (72%) race caucasian hispanic 21 (84%) 4 (16%) years of psoriasis 24 (13) data are mean (iqr) or n (%). table 1. baseline demographics disease characteristics  approximately half of the patients are being managed with ustekinumab as their biologic agent (table 2)  at enrollment, the patients were experiencing psoriasis disease activity that warranted either adding therapy or switching to a different biologic agent o based on pga, bsa, and pga x bsa scores o only 3 patients (12%) met the treat-to-target criterion of bsa ≤1% patients (n=25) biologics in use at baseline ustekinumab adalimumab secukinumab etanercept ixekizumab 13 (52%) 5 (20%) 5 (20%) 1 (4%) 1 (4%) pga 3 (2-3) bsa, % 3 (2-4) pga x bsa 8 (6-12) table 2. baseline disease characteristics data are median (sd) or n (%). iqr=interquartile range, representing the range of values between the 25th and 75th percentiles of the study population. conclusions  this study reveals that despite ≥24 weeks of stable biologic therapy for psoriasis, significant disease activity remains in this unique, real-world patient population, highlighting an unrecognized, unmet medical need  residual disease activity was demonstrated by several measures, including scores up to 4 for pga, 5 for bsa, and 16 for dlqi  patients with psoriasis desire disease clearance. the disease activity experienced by the patients in this study warrants additional treatment to better control the disease  the itching, burning, and dryness experienced by the majority of the patients compromised their quality of life  the effect of cal/bd foam in clearing residual disease activity for this unique patient population on stable biologic therapy is being investigated in this study  this study will help to better elucidate the disease characteristics and optimal management of this patient population quality of life and lesion description  the health-related quality of life of the patients continues to be affected by psoriasis despite ≥24 weeks of biologic therapy, as indicated by their dlqi scores (table 3)  itching and burning/stinging of the psoriatic lesions is present in the majority of the patients  40% of the patients experience dryness in their lesions, as observed by the investigator  none of the patients had skin atrophy, striae, telangiectasiae health-related quality of life of the patients, or folliculitis at baseline patients (n=25) dlqia 3 (1-4) psoriasis itching score ≥1a 17 (68%) psoriasis burning/stinging score ≥1a 5 (20%) psoriasis dryness score ≥1b 10 (40%) table 3. baseline observations data are median (iqr) or n (%). aas reported by the patient. bas observed by the investigator. acknowledgments and disclosures this study was supported by leo pharma editorial support was provided by p-value communications dr. bagel is an advisor, consultant, investigator, and speaker for abbvie, amgen, celgene, janssen, eli lilly, leo pharma, novartis, and regeneron; he is an investigator and consultant for pfizer and an investigator for valeant, lycera, ucb, and actelion; he is founder of windsor dermatology dr. keegan is an investigator and speaker for abbvie, janssen, eli lilly, novartis, pfizer, actelion, and valeant and a speaker for allergan and promius slide number 1 20201210_twyneo age analysis 0% 10% 20% 30% p er ce nt o f pa tie nt s ac hi ev in g ig a su cc es s at w ee k 12 microencapsulated benzoyl peroxide 3%, microencapsulated tretinoin 0.1% cream: efficacy for pediatric and adolescent patients stein gold, l¹, del rosso, j² 1. henry ford health systems, detriot, mi 2. jdr dermatology research, las vegas, nv introduction • benzoyl peroxide (bpo) is recommended for treatment of acne of all severities.1 it is bactericidal against c. acnes on the skin and within hair follicles with no risk for development of resistance,1,2 and it also has mild keratolytic effects.3 • bpo is widely used as a single agent in many different vehicles,4 and in combination with other medications.3,5 multiple analyses have indicated that the efficacy of bpo is enhanced when used in combination with topical retinoids, such as tretinoin.6,7 however, bpo usually causes degradation of tretinoin, reducing its effectiveness.8 results achievement of iga success • the efficacy of e-bpo/e-atra in pediatric and adolescent patients (9-17 years of age) was at least equivalent to that for the entire population. • e-bpo/e-atra is an investigational, antibiotic-free, fixed-dose combination cream containing microencapsulated bpo 3% (e-bpo) and microencapsulated tretinoin 0.1% (e-atra). the use of sol-gel’s microencapsulation technology platform provides a stable combination of bpo and tretinoin, extending drug delivery time, and reducing potential irritation caused by direct application of the drugs to the skin. • the efficacy, safety, and tolerability of e-bpo/e-atra have been demonstrated in two phase 3 randomized, vehicle-controlled trials.9 this result provides an analysis of the effectives of e-bpo/e-atra in patients of different ages based on analysis of results from those two studies, with a focus on pediatric and adolescent patients. • pooled results from the two phase 3 trials of e-bpo/e-atra demonstrated that this new microencapsulated formulation of bpo and tretinoin was efficacious in pediatric and adolescent patients who comprise a very large segment of the overall population with acne and about 45% of the patients in the phase 3 trials. conclusions • e-bpo/e-atra cream, combines, for the first time, two of the safest and most effective topical agents available for the treatment of acne into a single application. acknowledgments: the authors wish to recognize the support of robert rhoades, phd, and thomas prunty, cmpp, of aramed strategies, llc., for their editorial and scientific analysis support. their assistance was funded along with the studies represented herein, bysol-gel technologies, ltd. references: 1. zaenglein al, et al. j am acad dermatol. 2016;74:945-973 e933; 2. walsh tr, et al. lancet infect dis. 2016;16:e23-33; 3. matin t, goodman mb. 2019. available from http://www.ncbi.nlm.nih.gov/books/ nbk537220/; 4. kawashima m, et al. j dermatol. 2017;44:1212-1218; 5. kircik lh. j drugs dermatol. 2013;12:s73-76; 6. sagransky m, et al. expert opin pharmacother. 2009;10:2555-2562; 7. fakhouri t, et al. j drugs dermatol. 2009;8:657-661; 8. martin b, et al. br j dermatol. 1998;139 (suppl 52):8-11; 9. del rosso j, et al. presented at maui derm. 2020. to interact with and explore these data more intimately, please click here: https://www.solgelposters.com methods design reduction in inflammatory lesions • the efficacy of e-bpo/e-atra in pediatric and adolescent patients (9-17 years of age) was at least equivalent to that for the entire population. reduction in non-inflammatory lesions • the efficacy of e-bpo/e-atra in pediatric and adolescent patients (9-17 years of age) was at least equivalent to that for the entire population. 2x trials / 12 weeks / 63 sites acrossus • two multicenter, randomized, double-blind, parallel-group vehicle-controlled trials (sgt-65-04 and sgt-65-05) carried out at 63 sites across the united states (figure 1). figure 1. study design • age ≥9 years • ≥20 to ≤100 inflammatory lesions • ≥30 to ≤150 non-inflammatory lesions • iga grade 3 (moderate) or grade 4 (severe) • cysts/nodules ≤2 in cl us io n cr ite ri a randomization baseline 2 4 weeks 8 12 12 weeks of treatment 63 total sites study 65 04: 424 study 65-05: 434 qd, self-applied vehicle cream e-bpo/e-atra cream (3% e-bpo, 0.1% e-atra) 2:1 e-atra, microencapsulated tretinoin; e-bpo, microencapsulated benzoyl peroxide; iga, investigator’s global assessment; qd, once daily. endpoints • co-primary efficacy endpoints ▪ proportion of patients who achieved a two-grade reduction from baseline and grade 0 (clear) or grade 1 (almost clear) at week 12 on a 5-point iga scale. ▪ absolute change in inflammatory lesion counts from baseline at week 12. ▪ absolute change in non-inflammatory lesion counts from baseline at week 12. data analysis • all efficacy analyses were carried out using the intent-to-treat population. safety analyses were carried out using the safety population. • all results are reported as effects of e-bpo/e-atra vs vehicle (point estimates of the difference between treatments). iga treatment success at week 12 40% m ea n re du ct io n in in fla m m at or y le si on c ou nt fr om b as el in e at w ee k1 2 absolute mean change from baseline in inflammatory lesions at week 12 33.3% 14.9% 32.2% 34.2% 18.1% 10.6% -18.9 -14.3 -19.1 -18.8 -15.5 -12.8 age: 0 -2 -4 -6 -8 -10 -12 -14 -16 -18 -20 absolute mean change from baseline in non-inflammatory lesions at week 12 e-bpo/ vehicle e-atra (n=287) (n=571) age: e-bpo/ vehicle e-atra (n=124) (n=264) e-bpo/ e-atra (n=307) all p<0.0001 ≥18 p=0.0002 all 9-17 ≥18 vehicle (n=163) m ea n re du ct io n in in fla m m at or y le si on c ou nt fr om b as el in e at w ee k1 2 -27.2 -18.5 -28.9 -25.8 -21.1 -15.1 age: 0 -3 -6 -9 -12 -15 -18 -21 -24 -27 -30 all 9-17 ≥189-17 p<0.0001 e-bpo/ e-atra (n=571) vehicle (n=287) p<0.0001 e-bpo/ e-atra (n=264) vehicle (n=124) e-bpo/ e-atra (n=307) vehicle (n=163) p<0.0001 p=0.0055 e-bpo/ e-atra (n=571) vehicle (n=287) p<0.0001 p<0.0001 e-bpo/ e-atra (n=264) vehicle (n=124) e-bpo/ e-atra (n=307) vehicle (n=163) p=0.0013 http://www.ncbi.nlm.nih.gov/books/ microencapsulated benzoyl peroxide 3%, microencapsulated tretinoin 0.1% cream: efficacy for pediatric and adolescent patients skin september 2017 volume 1 issue 2 copyright 2017 the national society for cutaneous medicine 91 brief articles hypertrophic lichen planus versus well-differentiated squamous cell carcinoma: a histological challenge samuel p. haslam, md a lindy s. ross, md b alison c. lowe, md b brent c. kelly, md b a preliminary medicine, b department of dermatology, university of texas medical branch, galveston, tx a 74-year-old woman presented with a 3 month history of an itchy rash on the dorsal forearms and left anterior shin. physical exam revealed violaceous scaly papules and plaques along the dorsal forearms, as well as a hyperpigmented verrucous plaque with nodules along the left anterior shin (figure 1). initial biopsy of the left anterior shin revealed well-differentiated squamous cell carcinoma (scc, figure 2); however, due to a clinical appearance consistent with hypertrophic lichen planus (lp), three more biopsies were taken. two of these were read as hypertrophic lp, while the third was analyzed as a non-specific squamous proliferation. the initial biopsy was subsequently re-classified as pseudoepitheliomatous hyperplasia (peh), and the patient was diagnosed with hypertrophic lp and underwent improvement with clobetasol and kenalog treatment. a 55-year-old female on hemodialysis for chronic kidney disease presented with a 7 month history of an itchy rash on the extremities and back. physical exam revealed many excoriated papules and nodules along with some lichenified, flattopped papules throughout all of these abstract differentiating hypertrophic lichen planus (lp) from well-differentiated squamous cell carcinoma (scc) is a histological challenge given the numerous histopathologic similarities between scc and pseudoepitheliomatous hyperplasia (peh) arising in the setting of hypertrophic lp. multiple reports have shown that scc can arise from hypertrophic lp not infrequently, but that the lp-to-scc sequence is poorly understood, and many cases defy diagnosis due to histologic similarities. however, there are several clinical clues and histopathologic details that have shown to have some value when trying to ascertain the correct diagnosis. to the contrary, immunohistochemical tests have shown little promise in differentiating hypertrophic lp from scc. although multiplex pcr has shown some potential in differentiating peh from scc, this has only been in the setting of patients diagnosed with prurigo and lichen simplex chronicus, but not necessarily in the case hypertrophic lp. case descriptions skin september 2017 volume 1 issue 2 copyright 2017 the national society for cutaneous medicine 92 areas. additionally, three 1.3-1.5 centimeter pink nodules were noted on the lower legs (figure 3). biopsies of the nodules were taken, and although the patient's clinical appearance was consistent with hypertrophic lp, the nodules were diagnosed as well-differentiated scc's, and were treated as such. figures figure 1: hyperpigmented verrucous plaque with nodules along the left anterior shin, suspicious for hypertriphic lichen planus. figure 2: biopsy of the above lesion was initially read as welldifferentiated squamous cell carcinoma, but the diagnosis was revised to pseudoepitheliomatous hyperplasia arising in the presence of hypertrophic lichen planus upon clinical review and additional biopsies. figure 3: nodules suspicious for squamous cell carcinoma arising in the setting of hypertrophic lichen planus. skin september 2017 volume 1 issue 2 copyright 2017 the national society for cutaneous medicine 93 ninety-one total cases of the lp-to-scc transition have been reported, and over 50 of them have occurred in the context of hypertrophic lp 1 . features unique to the growth of scc in the context of lp include that the lesions tend to present below the knee, are more frequent in male patients, and the average age is older than 55 2 . likewise, authors have reported a 0.4% incidence of malignancy for cutaneous lp, and noted that chronicity is a risk factor for malignant transformation, as the typical lp patient is afflicted for more than 11 years before malignancies tend to develop. similarly, multiple studies have commented on the difficulty of differentiating scc from peh arising from hypertrophic lp histologically, and a multitude of prior cases have been reported in which the preliminary diagnosis of scc was reversed to hypertrophic lp following supportive clinical evidence 1,3 . in the majority of these cases the lesions showed significant improvement with near-resolution by 6 months following treatment with topical steroids 1 . likewise, in each of these cases the histologic diagnosis was reversed from scc to peh, which can be the result of many different chronic inflammatory processes and is characterized by gross acanthosis, moderate dyskeratosis, and downward proliferation with horn cysts on histology. however, in peh, lymphovascular and perineural invasion is absent, and there is no inclusion of the deep dermis. identifying scc's in the context of hypertrophic lp has been a common difficulty since the lp-to-scc sequence is poorly understood histologically; as such, many cases of scc arising in hypertrophic lp may not initially be accepted as such 4 . however, it is equally easy to misidentify peh as scc, particularly in the context of superficial shave biopsies. histologic clues that may differentiate hypertrophic lp from scc include the presence of a lichenoid infiltrate at the tips of the rete ridges along with dyskeratosis, pigment incontinence, and lack of cytologic atypia 5 . however, since peh can present with "irregular strands, cords, and nests of squamoid cells extending into the dermis" along with "substantial nuclear atypia and mitoses," some cases can simply "defy definitive classification" 6 . in regards to immunohistochemistry, p53 expression is seen in all cases of peh and 75% of scc cases, although the staining pattern is less intense and extensive in peh as compared to scc 4 . additionally, both stain similarly to proliferating cell nuclear antigen, and although e-cadherin has been reported to be lost in scc but preserved in peh, it has been found to stain both peh and scc samples equally. furthermore, although there are decreased langerhans cells compared to normal epidermis in peh, scc also has reduced numbers of cd1-a positive cells. although p63 was used for one case to distinguish peh from scc in the case of a granular cell tumor of the tongue, it has not yet been used for lp 7 . lastly, ki-67 has been found to be present in the basal layer of both peh and scc 4 . due to the lack of immunohistochemical differences, it has been suggested that the presence of multiple lesions, clinical followup, and proliferation from follicular infundibula are the most reliable markers to point towards peh rather than scc. to address the problem that there have not been immunohistochemical or molecular tests to date to differentiate scc from peh, multiplex pcr was tested and shown to differentiate cutaneous scc from peh in 53 of 58 cases (93%) 6 . the genes c15orf48 discussion skin september 2017 volume 1 issue 2 copyright 2017 the national society for cutaneous medicine 94 and krt9 have been found to have distinct gene expression patterns in scc and peh, with c15orf48 having a higher expression than krt9 in scc, but lower in peh. however, in the aforementioned research, the peh cases were selected from patients diagnosed with prurigo or lichen simplex chronicus, so the generalizability of the study to the case of peh arising in the setting of cutaneous lp is unknown. in summary, transition from cutaneous lp to scc is somewhat rare, with less than 100 reported cases in total, but over half of these cases have arisen in the context of hypertrophic lp 1 . many cases of scc may be missed since there is not a well-known cutaneous lp-to-scc histologic sequence, but it is very difficult to differentiate scc from peh arising in the context of hypertrophic lp, and many cases may lie in a "grey zone" due to histologic similarities 4 . however, histologic clues that point to peh include a lichenoid infiltrate at the tips of the rete ridges along with dyskeratosis, pigment incontinence, lack of cytologic atypia, and proliferation from follicular infundibula 4,5 . furthermore, clinical clues such as response to steroids and multiplicity and acuity of lesions may be more useful than histopathology to indicate peh rather than scc 1,3,4 . conflict of interest disclosures: none. funding: none. corresponding author: samuel p. haslam md 106 mechanic st., apt. 92 galveston, tx 77550 phone: 816-288-3703 e-mail: sphaslam@utmb.edu references: 1. nguyen r, murray b, mccormack c. hypertrophic lichen planus: masquerading as squamous cell carcinoma. clinical dermatology. 2014;2(3):136-9. 2. knackstedt tj, collins lk, li z, yan s, samie fh. squamous cell carcinoma arising in hypertrophic lichen planus: a review and analysis of 38 cases. dermatol surg. 2015;41(12):1411-8. 3. tan e, malik r, quirk cj. hypertrophic lichen planus mimicking squamous cell carcinoma. australas j dermatol. 1998;39(1):45-7. 4. pusiol t, zorzi mg, morichetti d, speziali l. pseudoepitheliomatous hyperplasia arising from hypertrophic lichen planus mimicking squamous cell carcinoma: limited value of immunohistochemistry. acta dermatovenerol croat. 2012;20(2):112-25. 5. deal t, mishra v, duong b, andea a. pitfalls in dermatopathology: when things are not what they seem. expert rev dermatol. 2012;7(6):579-88. 6. su a, ra s, li x, zhou j, binder s. differentiating cutaneous squamous cell carcinoma and pseudoepitheliomatous hyperplasia by multiplex qrt-pcr. modern pathology. 2013;26;1433-7. 7. bedir r, yilmaz r, sehitoglu i, ozgur a. coexistence of granular cell tumor with squamous cell carcinoma on the tongue: a case report. iran j otorhinolaryngol. 2015;27(78):69-74. acknowledgments all authors participated in the development of the poster and approved the final poster for presentation. editorial assistance in the development of this poster was provided by jessica donaldson-jones of fishawack communications ltd, abingdon, uk. this poster was previously presented at the european academy of allergy and clinical immunology congress, june 17–21, 2017, helsinki, finland, and at the fall clinical dermatology conference, october 12–15, 2017, las vegas, nv, usa. funding this study was funded by novartis pharmaceuticals canada inc. disclosures authors declare the following, real or perceived conflicts of interest: gs, jh, wg, cl, and why received honoraria as investigators and consultants. gs received honoraria as speaker of this corresponding study. oc, fdt, and lr are employees of novartis pharmaceuticals. gd was previously an employee of novartis pharmaceuticals. contact information lenka rihakova – lenka.rihakova@novartis.com. antonio vieira – antonio.vieira@novartis.com. novartis pharmaceuticals canada: +1(514) 631 6775 study design • optima is an international, multicenter, randomized, open-label, noncomparator study of two doses of omalizumab treatment (150 mg and 300 mg) across two dosing periods • in the initial dosing period, patients receive omalizumab by subcutaneous injection, at the randomized dose, every 4 weeks (figure 1) • subsequent dosing is determined based on the patient’s uas7 response (figures 2 and 3) • patients are eligible for the optima study if they are adults diagnosed with ciu/csu and have been exhibiting symptoms for at least 6 months prior to the study despite concurrent nonsedating h 1 -antihistamine therapy • refractory to antihistamine therapy is defined as uas7 ≥16 (scale 0−42) and itch component of uas7 ≥8 (scale 0−21) despite treatment with an approved dose of nonsedating h 1 -antihistamine and no other concomitant ciu/csu treatment for at least 7 consecutive days sample size and analysis sample size • the study has been planned to enroll and randomize a total of 320 patients, in a ratio of 4:3, to the doses of omalizumab 150 mg or 300 mg. the sample size is estimated on the basis of assessing the effect of retreatment following relapse (primary endpoint) conclusions • the optima study will allow better characterization of the appropriate omalizumab treatment regimen in patients with ciu/csu who relapse or are not well controlled after initial treatment, by answering the following questions: − if a patient is well controlled and therefore treatment is stopped, will the patient relapse? how long will it take to relapse? − if treatment is restarted, will the patient respond to retreatment? − if the patient does not respond to omalizumab 150 mg, will step-up therapy help? − if the patient does not respond to omalizumab 300 mg, will treatment extension help? objectives • primary: to assess the effect of optimized retreatment after relapse (defined as weekly urticaria activity score [uas7] ≥16) in patients with chronic idiopathic/spontaneous urticaria (ciu/csu) who were clinically well controlled (uas7 ≤6) following their first course of treatment with omalizumab • secondary: evaluation of dose step-up therapy in those who do not respond (uas7 >6) to an initial dose of omalizumab 150 mg; assessment of the time to relapse in patients who initially were well controlled (uas7 ≤6); and evaluation of the benefit of extending study treatment with omalizumab 300 mg in patients who are not yet clinically well controlled (uas7 ≤6) after 24 weeks • exploratory: evaluation of quality of life and occurrence of angioedema episodes design and rationale of the optima study: retreatment or step-up therapy with omalizumab in patients with chronic idiopathic/spontaneous urticaria (ciu/csu) gordon sussman,1 jacques hébert,2 wayne gulliver,3 charles lynde,4 william h. yang,5 olivier chambenoit,6 gretty deutsch,7 frederica detakacsy,8 lenka rihakova8 1department of medicine, university of toronto, toronto, on, canada; 2department of medicine, centre hospitalier de l’université laval, québec, qc, canada; 3faculty of medicine, memorial university of newfoundland, st. john’s, nl, canada; 4lynde institute for dermatology, markham, on, canada; 5ottawa allergy research corporation, university of ottawa medical school, ottawa, on, canada; 6novartis pharmaceuticals corporation, east hanover, nj, usa; 7previously novartis pharmaceuticals canada inc., dorval, qc, canada; 8novartis pharmaceuticals canada inc., dorval, qc, canada scan this qr code visit the web at: http://novartis.medicalcongressposters.com/default.aspx?doc=c50fe mobile friendly e-prints 3 ways to instantly download an electronic copy of this poster to your mobile device or e-mail a copy to your computer or tablet text message (sms) text: qc50fe to: 8nova (86682) us only +18324604729 north, central and south americas; caribbean; china +447860024038 uk, europe & russia +46737494608 sweden, europe standard data or message rates may apply. screen & washout omalizumab 150 mg omalizumab 300 mg g ro u p a g ro u p b followup uas7 ≤6 uas7 <16 stop therapy r a n d o m iz a ti o n 4 :3 −5 to −1week 0 4 8 12 16 2420 0 4 8 12 0 4 uas7 ≤6 uas7 <16 stop therapy screen 1st dosing 2nd dosing 0 4 8 uas7 >6 uas7 ≥16 uas7 ≥16 uas7 >6 omalizumab 150 mg omalizumab 300 mg omalizumab 300 mg omalizumab 300 mg followup study treatment withdrawal figure 1. optima study design. the study includes five phases: screening; initial dosing period; withdrawal; a second dosing period for retreatment, dose step-up, or dose extension based on uas7 response; and follow-up. uas7, weekly urticaria activity score. controlled/ mild uas7 ≤16 moderate/ severe uas7 ≥16 omalizumab 150 mg 0 4 8 12 16 2420 0 4 8 0 412 w e ll c o n tr o ll e d w it h o u t re la p s e weeks w e ll c o n tr o ll e d w it h re la p s e n o t w e ll c o n tr o ll e d follow-up follow-up follow-up omalizumab 150 mg 0 4 8 1st dosing study treatment withdrawal 2nd dosing followup controlled at every visit from week 8 to week 24 uas7 ≤6 controlled at every visit from week 8 to week 24 uas7 ≤6 not controlled uas7 >6 figure 3. dosing scenarios for the omalizumab 150 mg treatment group. patients who are well controlled (uas7 ≤6) in the 24-week initial dosing period enter the 8-week withdrawal period and then the follow-up phase if they remain well controlled. if relapse (uas7 ≥16) occurs during the withdrawal period, patients are retreated in a second dosing period at the same omalizumab 150 mg dose for 12 weeks. if symptoms are not well controlled (uas7 >6) during the initial omalizumab 150 mg dosing period, then patients step up to the omalizumab 300 mg dose at any protocol visit as early as week 8 to start the second dosing period. uas7, weekly urticaria activity score. controlled at week 24 – uas7 ≤6 controlled/ mild uas7 ≤16 moderate/ severe uas7 ≥16 omalizumab 300 mg 0 4 8 12 16 2420 0 4 8 0 412 w e ll c o n tr o ll e d w it h o u t re la p s e weeks w e ll c o n tr o ll e d w it h re la p s e n o t w e ll c o n tr o ll e d follow-up follow-up follow-up omalizumab 300 mg 0 4 8 1st dosing 2nd dosing controlled at week 24 – uas7 ≤6 not controlled at week 24 – uas7 >6 study treatment withdrawal followup figure 2. dosing scenarios for the omalizumab 300 mg treatment group. patients who are well controlled (uas7 ≤6) in the 24-week initial dosing period enter the 8-week withdrawal period and then the follow-up phase if they remain well controlled. if relapse (uas7 ≥16) occurs during withdrawal, patients are retreated in a second dosing period at the same dose (omalizumab 300 mg) for 12 weeks. if symptoms are not well controlled (uas7 >6) in the initial dosing period, then patients extend treatment for 36 weeks of continuous omalizumab 300 mg treatment. uas7, weekly urticaria activity score. primary endpoint • proportion of patients that achieved uas7 ≤6 at the end of the second dosing period, after being clinically well controlled (uas7 ≤6) in the initial dosing period followed by relapse (uas7 ≥16) when treatment was discontinued secondary endpoints • difference in uas7 between start and end of the second dosing period in patients who stepped up treatment from omalizumab 150 mg to 300 mg • the proportion of patients that were clinically well controlled (uas7 ≤6) at the end of the second dosing period in patients who stepped up treatment from omalizumab 150 mg to 300 mg • the time to relapse (uas7 ≥16) after withdrawal of omalizumab in patients who were clinically well controlled following their first course of omalizumab treatment • difference in the uas7 between the end of the initial dosing period and the end of the second dosing period in patients who extended treatment with omalizumab 300 mg secondary endpoints (continued) • the uas7 change from baseline measured at the end of the initial dosing period in patients who received omalizumab 300 mg • the uas7 change from baseline measured at the end of the second dosing period in all patients • the proportion of patients that remain well controlled (uas7 ≤6) or that have achieved uas7 =0 at week 8 of the initial dosing period versus week 8 of the second dosing period • the proportions of patients who remain clinically well controlled (uas7 ≤6) at any visit starting at week 8 of the initial dosing period until the end of the first dosing period poster presented at the winter clinical dermatology conference, january 12–17, 2018, lahaina, hi, usa skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 347 clinical management recommendations how to discuss equivocal melanocytic neoplasms with patients clay cockerell md, mbaa acockerell dermatopathology, dallas, tx while fortunately relatively rare, occasionally a dermatologist will biopsy a pigmented lesion, submit it to the dermatopathologist and a diagnosis is rendered that is equivocal for one reason or another. one of the more perplexing cases is when it comes back as “atypical spitzoid melanocytic neoplasm,” especially when the patient is not a young child. as a clinical dermatologist and dermatopathologist, i have had experience in rendering these diagnoses as well as counseling patients who have received such diagnoses. while this has the potential to create confusion for many stakeholders, there is a reasonable way to deal with this. first, there are techniques that can increase accuracy of diagnosis such as fluorescence in situ hybridization (fish) and gene expression profiling (gep) that can add information that that leads the dermatopathologist to change the diagnosis from “atypical spitzoid neoplasm” to either melanoma or spitz’s nevus. this would resolve the problem right away. another option is to submit the specimen to an expert in the evaluation of melanocytic neoplasia for a second opinion. however in a number of cases, this information is also equivocal and does not allow a more definitive diagnosis to be made. just as in every other field of medicine, there are cases in which the diagnosis and/or prognosis is simply unclear. diseases “do not always read the textbook,” and medicine is simply not an exact science. i tell my patients that i recommend excising the lesion as widely as possible causing the least amount of deformity and follow them carefully as if the lesion could ultimately behave as a melanoma. while the gep performed by castle biosciences provides prognostic information, it is not recommended for equivocal lesions unless the diagnosis of melanoma has been rendered. some individuals have recommended sentinel lymphadenectomy when the lesion is 1mm or greater in thickness. if positive, the patient should be followed more intensely. there is data to indicate that even if an atypical spitzoid neoplasm or true “spitzoid” melanoma spreads to a lymph node, it may never spread further or cause significant harm to the patient.1 this should be stressed to patients who have a positive sentinel node result. how to strengthen the diagnosis what to tell patients and their families? skin november 2018 volume 2 issue 6 copyright 2018 the national society for cutaneous medicine 348 patients can be left with a myriad of high level concerns after a diagnosis of atypical spitzoid neoplasm. i spend significant personal time with the patient and do my best to explain the situation and outline an approach that offers the best possible outcome while conveying some degree of remaining uncertainty. the fact that many patients with these lesions do well even if there is evidence of lymph node involvement provides encouragement that things may not be as bad as they might seem. hopefully by following a similar approach, you can create cautious optimism and allay the understandable fear patients and their families will experience. after receiving an ambiguous diagnosis with uncertain prognosis, patients will have many questions for their dermatologists. given this, we suggest the following approaching when discussing these issues with patients: 1. convey to the patient the difficulty in making a definitive diagnosis. atypical spitzoid neoplasms represent a diagnostic challenge even to experienced pathologists as they are difficult to distinguish between a benign spitz nevus and a spitzoid melanoma. 2. offer new genetic tests, such as fish and gep, that can improve diagnostic accuracy and render a stronger diagnosis. 3. in cases where the diagnosis remains uncertain, wide excision with careful follow up is recommended. 4. the prognosis for these lesions may be quite good. many cases of true spitzoid melanoma may spread to a local lymph node yet never metastasize more widely. 5. spending time with patients and their families to discuss the issue is very helpful in helping them to understand the complexity of their case and assuage their fears. with the ubiquity of this topic in dermatology, questions from patients will invariably arise. using this framework, dermatologists will be more prepared to answer patient questions, dispel fears, and optimize patient outcomes. conflict of interest disclosures: dr. cockerell is a consultant for castle biosciences. funding: none. corresponding author: clay cockerell, md, mba cockerell dermatopathology dallas, tx references: 1. kelly l. harms, md, phd; lori lowe, md; douglas r. fullen, md; paul w. harms, md, phd. atypical spitz tumors. a diagnostic challenge. arch pathol lab med. 2015;139:1263–1270. what can dermatologists do to ease patient concerns? how to approach this issue with patients skin january 2019 volume 3 issue 1 copyright 2018 the national society for cutaneous medicine 13 in-depth reviews review of instructive cases from the zola cooper and lee t. nesbitt seminar etan marks, do1, leah persad, do1, clay j cockerell, md1 1cockerell dermatopathology, dallas, tx history: a 56 year old woman presented with a 4 month history of ulcerated plaques and nodules of the trunk and extremities (figure 1). she complained of no “b” symptoms. she had a past medical history of fibromyalgia, depression, asthma, and hypertension. she is currently on buspirone, gabapentin, losartan, pantoprazole, and venlafaxine. physical examination: scattered red papules and plaques with focal areas of necrosis and ulceration on the back of the neck, mid-back and legs. histopathology: band-like papillary dermal lymphoid infiltrate with epidermotropism comprised of large lymphocytes with irregular nuclei. the cells stained positively for cd3 and beta-f1, but were mostly negative for cd4, cd8, cd30, and cd56 (figure 2). tcell receptor gene rearrangements were positive for a clonal gamma t cell gene rearrangement. laboratory data: whole blood flow cytometry showed a cd4/cd8 ratio of 4.5. a leukemia/lymphoma panel showed no abnormality. serum t-cell receptor gamma gene rearrangement was negative. a cbc showed a wbc of 11.8 (slightly elevated) and platelet count of 456. a cmp showed no abnormalities. hiv and rpr tests were negative. however, pet/ct showed innumerable fdg-avid cutaneous lesions although no fdg-avid lymph nodes. clinical course: the patient was treated with prednisone 60mg daily and then tapered off as there was no improvement after 3 case 1 histopathological examination is considered to be the gold standard for diagnosis. however, research has shown that clinical correlation with pathological examination is crucial for the appropriate diagnosis. this is especially true in dermatology/dermatopathology where several entities can appear similar under the microscope, but are vastly different with their clinical presentation and vice versa. with this in mind, we mention the zola cooperlee t. nesbitt seminar that was established in 1954 and is the longest free standing clinical-pathologic conference still in existence. the purpose of the seminar is to serve as an educational conference designed to promote continuous excellence in the field of clinical dermatology and dermatopathology. herein, we present six cases that were presented at the conference which highlight the importance of the clinical-pathological correlation in the practice of dermatology. abstract skin january 2019 volume 3 issue 1 copyright 2018 the national society for cutaneous medicine 14 figure 1 figure 2 weeks. methotrexate was added at a dosage of 17.5mg weekly. the patient continues to develop new lesions with persistence of older lesions. diagnosis: cd4-/cd8t-cell lymphoproliferative disorder (ddx: probably primary cutaneous cd8+ aggressive epidermotropic cytotoxic t-cell lymphoma which is cd8in this case, with the possibility of an unusual mycosis fungoides) points of emphasis: the histopathological features of skin with prominent epidermotropism of atypical lymphocytes with clinically persistent plaques leads to a differential diagnoses that includes mycosis fungoides, primary cutaneous γ/δ t-cell lymphoma and primary cutaneous cd8+ aggressive epidermotropic cytotoxic t-cell lymphoma. often, these lesions can be differentiated by immunophenotyping with mf mostly showing a cd3+/cd4+/cd8-/bf1+ phenotype, primary cutaneous γ/δ t-cell lymphoma showing a cd3+/cd4-/cd8-/bf1phenotype, and primary cutaneous cd8+ aggressive epidermotropic cytotoxic t-cell lymphoma showing a cd3+/cd4-/cd8+/bf1+ phenotype. however, all three of these entities can show cd3+/cd4-/cd8-. cd4/cd8 double-negative type mf has been commonly reported and has an indolent clinical course like that of typical mf.i primary cutaneous cd8+ aggressive epidermotropic cytotoxic t-cell lymphoma can be cd4-/cd8 in some cases.ii finally, γ/δ t-cell lymphoma is usually cd4-/cd8-, but shows negativity for bf-1.iii our case showed a cd4-/cd8-/bf-1+ immunophenotype which excludes the diagnosis of a γ/δ t-cell lymphoma. however, the clinical course appears to be more aggressive due to the persistent plaques and multiple cutaneous fdg avid lesions. therefore, an unusual cd8primary cutaneous cd8+ aggressive epidermotropic cytotoxic t-cell lymphoma seems to be more likely than a cd4-/cd8mycosis fungoides. history: a 75-year-old woman presented with a 1 cm erythematous nodule on the right anterior shoulder (figure 3). the lesion had been present for an undetermined period of time. case 2 skin january 2019 volume 3 issue 1 copyright 2018 the national society for cutaneous medicine 15 figure 3 figure 4 physical exam: involving the right anterior shoulder was a 1 cm, round pink to erythematous smooth firm nodule. laboratory data: non-contributory histopathology: a biopsy of the lesion revealed dermal sheets of small round blue cells with uniform round nuclei, scant cytoplasm, relatively minimal pleomorphism but with many mitotic figures. the tumor was diffusely and strongly positive for cd99, showed rare positivity for synaptophysin and was negative for ema, pan-ck, cd45, sox10, sma, ck20, ttf-1, cd43, mum-1, tdt, cd34, and p40. cytogenetic and molecular testing of the tumor was positive for rearrangement of the ewsr1 (22q12) locus by fish (figure 4). an ewsr1/fli1 fusion transcript was detected by rt-dna amplification respectively. clinical course: the patient was found to have no evidence of systemic disease. diagnosis: primary cutaneous ewing sarcoma in an adult points of emphasis: ewing sarcoma (es) is a small round blue cell tumor that is closely related to the primitive neuroectodermal tumor (pnet) family. ewing sarcoma is typically a neoplasm that occurs in bone or soft tissue of children and young adults. rarely, it can present as a primary cutaneous neoplasm in adults.iv in this setting, the mean age is 22 years (range from 22 months to 77 years) with a nearly 2:1 female predominance. the median size of tumors reported was 2-3 cm most commonly on the extremities, followed by the head and trunk. radiologic and clinical correlation is essential to confirm that the lesion is small and confined to the skin rather than a metastasis or direct extension from deep soft tissue or bone. histopathology typically reveals a nodular or sheet-like proliferation of undifferentiated small round blue cells. in this setting, there is a wide range of differential diagnoses when occurring in an adult including merkel cell carcinoma, metastatic small cell carcinoma of the lung, lymphoma and small cell melanoma. v ancillary studies can help further differentiate these entities. es/pnet almost always characteristically show diffuse positivity for cd99 in a membranous pattern. rarely, merkel cell carcinomas and lymphoblastic lymphoma can express cd99 skin january 2019 volume 3 issue 1 copyright 2018 the national society for cutaneous medicine 16 so that other stains may be required to distinguish these, however. es/pnet may infrequently display focal positivity for pancytokeratin, s100, and neuroendocrine markers. based on the varied immunohistochemical pattern of staining, there can be some diagnostic confusion between these entities, in which morphological and clinical correlation can aid in the diagnosis. the characteristic chromosomal translocation in es/pnet t(11;22)(q24; q12) resulting in the ewsr1-fli1 fusion gene can greatly aid in the diagnosis. however, approximately 10% of es/pnet have variant translocations. rarely, the ewsr1 gene can be identified in other morphologically distinct entities as it has been described as a “promiscuous” gene.vi dual color break-apart ews fish probes can detect ewsr1 rearrangements regardless of the translocation variants. in this break-apart probe strategy, fluorosceinated probes normally flank the ewsr1 gene. in the nucleus, abnormal (separate) red and green fluorochromes signify disruption of one copy of the ewsr1 gene. in contrast, the normal allele is intact as evidenced by fused red and green signals indicating that the two probes are juxtaposed as a consequence of binding the same chromosomal locus. based on the relatively limited data in the literature on primary cutaneous ewing sarcoma, it appears to have a much better prognosis than its skeletal or deep soft tissue counterpart. it has been established that the 10-year probability of survival was 91% with rare chance of metastatic disease.vii in light of the excellent prognosis of this tumor when confined to the skin, some authors have suggested that surgical excision should be the primary mode of treatment with adjuvant therapy such as chemotherapy or radiotherapy playing a lesser role. history: a 73 year old male presented with a long standing lesion on the occipital scalp (figure 5). a shave biopsy was submitted as “concerning for melanoma.” physical examination: irregular dark pigmented lesion on the scalp within an area of diffuse erythema extending onto the forehead. laboratory data: non-contributory histopathology: there was a dense diffuse infiltrate of spindle and epithelioid cells with pigment scattered throughout the lesion. most of the neoplastic cells were closely opposed to one another and some were arranged in aggregations. there were a few dilated blood vessels but no irregular staghorn vessels with atypical cells in their lumina were noted (figure 6). a diagnosis of malignant melanoma >2.1 mm was initially rendered. the lesion was re-excised at which point features characteristic of angiosarcoma were identified with numerous, diffuse atypical irregular vessels with endothelial atypia seen throughout the dermis (figure 7). the submitting clinician was contacted and a request was made to review clinical photographs. immunohistochemical stains were performed on the original biopsy and stains for erg and cd31 were positive (figure 8) while stains for melan-a and sox10 were negative. of interest, one popular area originally sampled by shave case 3 skin january 2019 volume 3 issue 1 copyright 2018 the national society for cutaneous medicine 17 figure 5 figure 6 figure 7 figure 8 technique stained positively for s-100 protein. diagnosis: pigmented epithelioid angiosarcoma simulating melanoma clinical course: a re-excision was performed although there was diffuse involvement of lateral margins given the diffuse nature of the process. he was referred to radiation oncology for postoperative palliative radiotherapy. points of emphasis: angiosarcoma is an uncommon soft tissue neoplasm with a predilection for skin and superficial soft tissues. the epithelioid variant of angiosarcoma can sometimes be difficult to recognize and can mimic other neoplasms, usually epithelial lesions such as squamous cell carcinoma. viii in this case because the skin january 2019 volume 3 issue 1 copyright 2018 the national society for cutaneous medicine 18 lesion did not demonstrate significant vascular differentiation and had pigment which was probably hemosiderin, in the context of a clinical history of possible melanoma, the diagnosis of melanoma was made on the basis of morphology alone. it was only apparent on re-excision that the lesion truly represented angiosarcoma. of interest in this case, there was positive staining for s-100 protein which may be seen in some angiosarcomas which can further complicate the diagnosis. furthermore, the clinician noted only the pigmented papule and did not notice the larger, diffuse erythema which represented the more classic angiosarcoma. it is important for clinicians to consider angiosarcoma in the differential diagnosis of cutaneous malignancies in lesions on the scalp of older individuals, especially if there are erythematous, macular “bruise-like” areas. shave biopsies are often subject to sampling errors and malignancies such as angiosarcoma and other soft tissue neoplasms may demonstrate multiphasic patterns that may appear quite different within the same neoplasm. in this case, the biopsy sampled an epithelioid component that was not characteristic of angiosarcoma although it was recognizable as a malignancy. unfortunately, the treatment of angiosarcoma is difficult as the lesion is diffuse and is not usually surgically resectable. radiation therapy including brachytherapy may be useful for palliation although the prognosis remains extremely poor.ix history: a 58 year old caucasian man presented to the dermatology clinic for figure 9 figure 10 evaluation of a rash which had been present for about one year. he first noted redness and swelling in his legs, along with a scaly and pruritic eruption on the upper body. the rash generalized and involved most of the body. he had no history of asthma or atopy as a child (figure 9). he was diagnosed with atopic dermatitis by a referring physician and was treated with dupilumab with no improvement. physical examination: nearly confluent, erythematous thin scaly plaques on the arms and legs, with erythematous scaly papules (some follicular) on the back and abdomen. laboratory data: noncontributory histopathology: two biopsies were performed, both of which showed case 4 skin january 2019 volume 3 issue 1 copyright 2018 the national society for cutaneous medicine 19 psoriasiform epidermal hyperplasia irregular acanthosis and hyperkeratosis with small foci of spongiosis. both biopsies also demonstrated foci of acantholysis, with some dyskeratosis as well (figure 10). clinical course: patient was treated with triamcinolone ointment wet wraps and emollients, with some improvement. he will soon begin treatment with acitretin. diagnosis: pityriasis rubra pilaris with acantholysis points of emphasis: pityriasis rubra pilaris is an uncommon papulosquamous eruption with several different clinical variants having been described. x the most common type (type i) presents in adults with follicularbased, hyperkeratotic papules that spread inferiorly after starting on the upper body. patients often develop palmoplantar keratoderma. an atypical presentation in the adult involves follicular hyperkeratotic papules, with an eczematous or ichthyosiform appearance to the plaques on the legs. these patients often have a more generalized distribution with chronic disease. the histological findings in pityriasis rubra pilaris vary by the acuity of the eruption and are most characteristic during the acute phase. classic features include irregular acanthosis and a cornified layer with alternating orthokeratosis and parakeratosis. follicular ostia are plugged with keratin, and inflammation is sparse. foci of acantholysis, or acantholytic dyskeratosis, may be seen in approximately 20% of cases of pityriasis rubra pilaris.xi in this case, the original clinical history did not include a differential diagnosis of psoriasis or prp and the main histologic features identified were the acantholytic dyskeratosis which led to an initial diagnosis of grover’s disease. when the patient was presented at a clinical conference, it became apparent that the psoriasiform dermatitis was the most important feature and a diagnosis of prp with acantholysis was made. this emphasizes the importance of providing complete clinical information when submitting skin biopsies and in difficult cases, including clinical photographs or having the patient evaluated at a clinical conference as was done in this case can improve the accuracy of the diagnosis. history: a 79 year old hispanic woman with a history of hypertension, diabetes, and renal insufficiency presented to the hospital with complaints of new onset melena and hematemesis. she was noted to have a one year history of a rash which started on her back and later spread to involve the arms, legs, and chest (figure 11). she had some pruritus but no other symptoms, and she had not attempted any treatments other than cetirizine. she had a history of mild arthritis. physical examination: there were pink dermal papules coalescing into plaques on the chest and back. lichenified erythematous plaques were found on the elbows. around the first and second fingers, there were periungual skin-colored to pink papules. there was also abnormality of the knees with swelling and joint dystrophy. laboratory data: significant anemia with a hgb 6.3 histopathology: a punch biopsy from a papule on the back revealed a dense dermal infiltrate of epithelioid histiocytes with amphophilic “ground glass” cytoplasm in a nodular configuration (figure 12). case 5 skin january 2019 volume 3 issue 1 copyright 2018 the national society for cutaneous medicine 20 figure 11 figure 12 clinical course: the patient was admitted for an upper gi bleed, and an egd revealed a ulcerated mass in the antrum of the stomach. a biopsy of this mass showed changes of chronic reactive gastropathy as may be seen near an ulcer, but no neoplasm was noted. her bleeding stabilized with proton pump inhibitors. a repeat egd is planned for the future, with probable rebiopsy of the antral mass. diagnosis: multicentric reticulohistiocytosis points of emphasis: multicentric reticulohistiocytosis is a mucocutaneous papulo-nodular eruption formed by nodular accumulations of reticulohistiocytes in the skin. when papules coalesce into plaques, a cobblestone appearance can be seen. the papules tend to predominate around joint spaces and classically present with a beaded appearance in a periungual distribution. reticulohistocytes are epitheiloid histiocytes with abundant amphophilic cytoplasm having a ground-glass texture. such histiocytes may be seen in isolated/solitary lesions (reticulohistiocytoma) or in diffuse eruptions (diffuse cutaneous reticulohistiocytosis). in the diffuse form, patients often develop a destructive arthropathy. solid internal malignancies are found in association in approximately 20% of cases.xii,xiii in this case, the diffuseness of the process was striking and given the extent of the process, many of the areas appeared more like a papulosquamous disorder rather than a widespread granulomatous process. while she had evidence of large joint involvement, she did not have the usual mutilating, destructive arthropathy that often involves smaller joints such as those of the hand. history: a 62-year-old woman with a history of hypertension was started on a new medication, diltiazem er, and developed a diffuse pruritic eruption 13 days later (figure 13). initially, the eruption was treated with an intramuscular injection of ceftriaxone and dexamethasone along with oral clindamycin, fluconazole, and oral hydroxyzine with topical mupirocin ointment. physical exam: involving the bilateral axillae, inguinal folds, trunk, and focally on the extremities are discrete and coalescing, focally round and targetoid erythematous to violaceous minimally scaling macules, case 6 skin january 2019 volume 3 issue 1 copyright 2018 the national society for cutaneous medicine 21 patches, and thin plaques. there were no associated systemic symptoms. laboratory data: non-contributory histopathology: punch biopsies from the back revealed psoriasiform dermatitis with overlying parakeratosis and focal mounds of neutrophils in the stratum corneum. involving the superficial dermis, there were a few scattered interstitial eosinophils, neutrophils, and extravasated red blood cells (figure 14). clinical course: the patient slowly improved after diltiazem er was discontinued. diagnosis: urticarial drug reaction with psoriasiform features consistent with symmetric drug-related intertriginous and flexural exanthema. points of emphasis: symmetric drugrelated intertriginous and flexural exanthema (sdrife) is a form of systemic allergic dermatitis induced by a systemically administered drug. this eruption was previously called “baboon syndrome” as it commonly occurs on the buttocks as well as the intertriginous areas of the body. betalactam antibiotics are the leading offending medication with case reports also including clarithromycin, doxycycline, metronidazole, infliximab, golimumab, and many more.xiv,xv,xvi,xvii clinically, the eruption is characterized by moderately ill-defined erythematous patches or thinly scaling plaques in intertriginous areas (axillae, groin, neck) as well as scattered on the trunk and extremities. rarely, there may be pustulobullous lesions also. the eruption may develop within a few hours up to 2 weeks after the drug has been administered. the differential diagnosis figure 13: figure 14: includes a morbilliform drug eruption, inverse psoriasis, intertrigo, atopic dermatitis, and acute generalized exanthematous pustulosis. the clinical history of a possible offending medication is necessary to making this diagnosis. histopathologically, sdrife has been described to show non-specific inflammatory findings including mild spongiosis, focal skin january 2019 volume 3 issue 1 copyright 2018 the national society for cutaneous medicine 22 vacuolar change, necrotic keratinocytes, a superficial perivascular lymphocytic infiltrate with interstitial dermal eosinophils and neutrophils. it is thought that most of these reactions are a type iv delayed hypersensitivity reaction mediated by cytotoxic t cells. in this interesting clinical case, the patient demonstrated the symmetric intertriginous eruption with focal areas resembling a fixed drug eruption clinically with mostly nonspecific psoriasiform changes on histopathology. identifying and discontinuing the causative medication is imperative. patch testing is possible but may have limited utility as there is limited absorption through the skin versus systemically and may not elicit a reaction. controlled oral provocation testing has been thought to be useful in confirming the diagnosis. along with discontinuation of the drug, oral anti-histamines and topical corticosteroids can be used. references: the zola cooperlee t. nesbitt seminar highlights the importance of dermatologists correlating their clinical findings to that which 1. i hodak e, david m, maron l, aviram a, kaganovsky e, feinmesser m. cd4/cd8 double-negative epidermotropic cutaneous tcell lymphoma: an immunohistochemical variant of mycosis fungoides. j am acad dermatol 2006; 55: 276–284. 2. ii toshinari miyauchi, riichiro abe, yusuke morita, et al. cd4/cd8 double-negative t-cell lymphoma: a variant of primary cutaneous cd8+ aggressive epidermotropic cytotoxic tcell lymphoma? acta dermato-venereologica. 2015;95(8):1024-1025. is seen under the microscope. here we highlight 6 cases from this excellent seminar that demonstrate the significance of synthesizing both aspects for an appropriate diagnosis. this seminar is open to all dermatologists/dermatopathologists and benefits from cases that are submitted from all over. the upcoming conference will be held november 2, 2019 in new orleans, louisiana. all are invited to attend and share their knowledge and interesting cases. conflict of interest disclosures: none. funding: none. acknowledgements: we would like to thank all of those who participated and contributed to the zola cooperlee t. nesbitt seminar. we would like to give special thanks to those who contributed to these six specific cases: patrick mcdonough md, adean kingston md, travis vandergriff md, ilka netravali md, heather goff md, jennifer day md, jennifer gill md, phd, amit patel md, jerad gardner md, and carolyn lyde md. corresponding author: etan marks, do cockerell dermatopathology dallas, tx cjcconsults@gmail.com 3. iii guitart j, weisenburger dd, subtil a, kim e, wood g, duvic m, et al. cutaneous gammadelta t-cell lymphomas: a spectrum of presentations with overlap with other cytotoxic lymphomas. am j surg pathol (2012) 36:1656–65. 4. iv delaplace m, lhommet c, de pinieux g, vergier b, de muret a, machet l. primary cutaneous ewing sarcoma: a systematic review focused on treatment and outcome. br j dermatol. 2012 apr;166(4):721-6. 5. v machado i, traves v, cruz j, llombart b, navarro s, llombart-bosch a. superficial small conclusion mailto:cjcconsults@gmail.com skin january 2019 volume 3 issue 1 copyright 2018 the national society for cutaneous medicine 23 round-cell tumors with special reference to the ewing's sarcoma family of tumors and the spectrum of differential diagnosis. semin diagn pathol. 2013 feb;30(1):85-94. 6. vi boland jm, folpe al. cutaneous neoplasms showing ewsr1 rearrangement. adv anat pathol. 2013 mar;20(2):75-85. 7. vii collier ab 3rd, simpson l, monteleone p. cutaneous ewing sarcoma: report of 2 cases and literature review of presentation, treatment, and outcome of 76 other reported cases. j pediatr hematol oncol. 2011 dec;33(8):631-4 8. viii prescott rj, banerjee ss, eyden bp, haboubi ny. cutaneous epithelioid angiosarcoma: a clinicopathological study of four cases. histopathology 1994;25 (5): 421– 429. 9. ix bacchi ce, silva tr, zambrano e, et al. epithelioid angiosarcoma of the skin. am j surg pathol 2010;34:1334–43 10. x magro cm, crowson an. the clinical and histomorphological features of pityriasis rubra pilaris. a comparative analysis with psoriasis. j cutan pathol 1997;24:416-24. 11. xi avitan-hersh e, bergman r. the incidence of acantholysis in pityriasis rubra pilarishistopathological study using multiple-step sections and clinicopathologic correlations. am j dermatopathol. 2015 oct;37:755-8. 12. xii kumar b, singh n, rahnama-moghadam s, wanat ka, ijdo jw, werth vp. multicentric reticulohistiocytosis: a multicenter case series and review of literature. j clin rheumatol 2018;24:45-49. 13. xiii selmi c, greenspan a, huntley a, gershwin me. multicentric reticulohistiocytosis: a critical review. curr rheumatol rep. 2015;17:511. 14. xiv dogru m, ozmen s, ginis t, duman h, bostanci i. symmetrical drug-related intertriginous and flexural exanthema (baboon syndrome) induced by amoxicillinclavulanate. pediatr dermatol. 2012 novdec;29(6):770-1 15. xv nespoulous l, matei i, charissoux a, bédane c, assikar s. symmetrical 16. drug-related intertriginous and flexural exanthema (sdrife) associated with pristinamycin, secnidazole, and nefopam, with a review of the literature. contact dermatitis. 2018 jul 30. doi: 10.1111/cod.13084 17. xvi labadie jg, florek ag, croitoru a, liu w, krunic al. first case of symmetrical drugrelated intertriginous and flexural exanthema (sdrife) due to berberine, an over-thecounter herbal glycemic control agent. int j dermatol. 2018 sep;57(9):e68-e70 18. xvii ozkaya e, babuna g. a challenging case: symmetrical drug related 19. intertriginous and flexural exanthem, fixed drug eruption, or both? pediatr dermatol. 2011 nov-dec;28(6):711-4 skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 118 rising derm stars® skinspecs: a solution that addresses an unmet need for tracking chronic skin diseases in the office and at home olga afanasiev, md, phd1, mika tabata, bs, akhila narla, ba, justin ko, md, mba 1department of dermatology, stanford university, stanford, ca background/objectives: chronic skin diseases are challenging and frustrating for both patients and physicians. patients often have difficult-to-capture flares in between visits and they are seeing multiple providers for their skin condition. while there are many emerging tools for monitoring individual neoplasms, our field lacks an objective and efficient tool to robustly document and longitudinally monitor changes in chronic skin conditions. this study identifies an unmet need in dermatology, performs an indepth stakeholder analysis and proposes a mobile-based imaging solution that has the potential to drastically change our current workflow and disease monitoring strategies to potentially improve patient care and outcomes. methods: stanford dermatology department attending physicians (n=14), residents (n=14) and patients (n=8) were surveyed to assess the need in our field for a new way to document and follow chronic skin diseases over time. skinspecs is an imaging-based solution that uses a smartphone camera to capture a short (~30 second) 180°-360° video of the full distribution of skin disease (no special setup required). this video was rendered using modified agisoft photogrammetry software to create a 3d model of the patient that can be viewed on any device. results: dermatologists use subjective measures to document chronic skin conditions (such as psoriasis): most dermatologists’ documentation of rashes relies on “gestalt” (70% of providers), descriptive exam (80%), and bsa (90%). notably, prior literature showed that bsa is poorly estimated by physicians1-2. validated scoring systems (such as pasi) or photographs are rarely used for documentation of rashes (7% and 18% respectively). at a follow up visit, dermatologists lack confidence in assessing disease change if patient was seen by another provider: while most dermatologists (82%) are confident in the assessment of disease change in their long-term patients, only 33% of providers are confident in their assessment of disease based on prior documentation by another provider. dermatologists want a better workflow for documenting chronic skin diseases in the office and in between visits: sixty percent of providers stated they need a better way of documenting chronic skin conditions in the office, and 60% stated they would like their patients to document their skin condition at home. patients want to document their skin disease at home: 100% of patients said it was important or very important to track their chronic disease at home and they are willing to spend 10-15 minutes weekly-monthly for documentation, with a preference of using a skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 119 smartphone. dermatologists preferred a 3d reconstruction (skinspecs) over written description, standard photographs or video capture for documenting and tracking chronic skin conditions: skinspecs is favorably used by dermatologists, with high satisfaction with resolution, breadth of visual information, time and ability to pick up incidental findings. conclusion: we identified a need and proposed a solution to objectively and robustly capture skin disease, with an office and home workflow that is acceptable for providers and patients. this fast, scalable method is deployable on smartphones and could be utilized to augment clinical decision making. figure 1: skinspecs algorithm from video to 3d reconstruction. a: extraction of relevant frames from video for 3d reconstruction. b-d: 3d reconstruction model of a subject, can be manipulated using adobe acrobat reader or other freely available applications. references: 1. ramsay b, lawrence cm. measurement of involved surface area in patients with psoriasis. br j dermatol. 1991;124(6):565570. 2. nichter ls, williams j, bryant ca, edlich rf. improving the accuracy of burn-surface estimation. plast reconstr surg. 1985;76(3):428–33. skin december 2018 volume 2 supplemental issue copyright 2018 the national society for cutaneous medicine 112 rising derm stars staphylococcus aureus nasal colonization is associated with severity of radiation dermatitis in patients receiving radiotherapy alexandra k. rzepecki, bs1 1university of michigan medical school, ann arbor, mi introduction: acute radiation dermatitis (rd) is a common adverse effect of radiation therapy (rt)1,2. up to 95% of patients undergoing radiotherapy develop some degree of rd. radiation-induced skin changes are thought to increase the risk of secondary skin infection. however, little is known regarding the baseline incidence of microbial colonization prior to rt and whether it is associated with development of rd. objective: the goals of our prospective study were to 1) characterize the incidence of baseline bacterial colonization in patients undergoing rt, and 2) examine the association between radiation dermatitis severity and baseline bacterial colonization. we hypothesize that microbial colonization prior to initiation of rt is associated with development of rd. methods: we conducted a prospective noninterventional trial at montefiore einstein center for cancer care in the bronx, new york between july 2017 to june 2018. patients undergoing radiotherapy for treatment of cancers of the head and neck, breast, or anus underwent bacterial culture from the nares and irradiated skin prior to rt initiation and again upon treatment completion. patients were evaluated weekly during rt, and dermatitis was graded using ctcae version 4.03. odds ratios were utilized to present associations between culture results and skin toxicity. results: eighty-three subjects with cancers of the breast (49%), head and neck (45%), and anus (6%) completed rt (table 1). all subjects developed some degree of rd: 59% grade 1, 33% grade 2, and 8% grade 3 dermatitis. baseline bacterial culture was positive for staphylococcus aureus (sa) in 17 subjects in the nares and in 5 subjects on the irradiated skin. all subjects with positive baseline skin cultures for sa also had a positive baseline nares culture for sa. a positive baseline nares culture was associated with increased risk of developing grade 2-3 dermatitis (65% vs. 34%, or=3.6, p=0.025) (figure 1). out of 64 patients with negative baseline nares cultures, 8 were found to have positive cultures for sa in the nares at later time points. among patients with negative cultures at baseline, finding positive cultures at a later time point was not significantly associated with development of grade 2+ dermatitis (50% vs. 32%, or=2.11, p=0.327). discussion: bacterial colonization with sa prior to initiation of rt is a risk factor for development of higher grade rd. because a positive nares culture was able to predict skin toxicity, even in the absence of a positive skin skin december 2018 volume 2 supplemental issue copyright 2018 the national society for cutaneous medicine 113 culture, it is possible that bacterial colonization in the nares plays a role in the pathogenesis of rd. sa colonization has been shown to have a role in inflammatory skin disorders similar to rd, such as atopic dermatitis3,4; thus, it is possible sa colonization prior to rt may facilitate skin barrier defects and drive inflammation, contributing to increased severity of rd. antimicrobial therapy in the nares prior to initiation of rt may be a strategy to lessen the severity of rd5. further studies are needed to understand the association between microbial colonization and development of rd, as well as the role of specific staphylococcal toxins in the pathogenesis of rd. table 1: patient demographics and results. total patients n = 83 gender: n % male 23 27.7% female 50 60.2% type of cancer n % breast 41 49% head & neck 37 45% anal 5 6% most severe grade 1—faint 49 59% grade 2— 27 33% grade 3—moist 7 8% baseline culture nares 17 21% skin 5 6% post-treatment nares 21 25% skin 14 17% figure 1. radiation dermatitis severity and nares bacterial colonization status at baseline. references: 1. singh m, alavi a, wong r, akita s. radiodermatitis: a review of our current understanding. am j clin dermatol. 2016;17(3):277-292. 2. leventhal j, young mr. radiation dermatitis: recognition, prevention, and management. oncol. 2017;31(12):885-899. 3. gong jq, lin l, lin t, et al. skin colonization by staphylococcus aureus in patients with eczema and atopic dermatitis and relevant combined topical therapy: a double-blind multicentre randomized controlled trial. br j dermatol. 155(4):680-687. 4. totté j.e.e., feltz w.t., hennekam m., belkum a., zuuren e.j., pasmans s.g.m.a. prevalence and odds of staphylococcus aureus carriage in atopic dermatitis: a systematic review and meta-analysis. br j dermatol. 2016;175(4):687-695. doi:10.1111/bjd.14566 chen af, wessel cb, rao n. staphylococcus aureus screening and decolonization in orthopaedic surgery and reduction of surgical site infections. clin orthop. 2013;471(7):2383-2399. doi:10.1007/s11999-013-2875-0 powerpoint presentation presented at 40th annual fall clinical dermatology conference, october 29–november 1, 2020 figure 4. secondary (a) and exploratory (b) efficacy endpoints at weeks 1 through 4 data presented for intent-to-treat population. only significant p-values (p<0.05) shown. ci: confidence interval; easi: eczema area and severity index; ls: least squares; viga-ad: validated investigator global assessment for atopic dermatitis. week 1 week 2 week 4 pa ti en ts , % viga-ad score of “clear” or “almost clear”(b) 60 50 40 30 20 10 0 easi percent change from baseline figure 2. absolute easi change from baseline at week 4 (primary endpoint) data presented for intent-to-treat population. ci: confidence interval; easi: eczema area and severity index; ls: least squares. figure 3. secondary (a, b) and exploratory (c) efficacy endpoints at week 4 data presented for intent-to-treat population. only significant p-values (p<0.05) shown. ci: confidence interval; easi: eczema area and severity index; ls: least squares; viga-ad: validated investigator global assessment for atopic dermatitis. introduction • majority of patients with atopic dermatitis are treated with topical anti-inflammatory therapy: corticosteroids or calcineurin inhibitors, in combination with emollients1 – side effects and poor adherence limit long-term use of topical corticosteroids – topical calcineurin inhibitors may cause local tolerability reactions • phosphodiesterase-4 (pde-4) is the predominant cyclic adenosine monophosphate–degrading enzyme in inflammatory cells, including lymphocyte subsets, and has increased activity in inflammatory skin disorders like atopic dermatitis2,3 • roflumilast cream is a highly potent pde-4 inhibitor with ~25to >300-fold higher potency than other approved pde-4 inhibitors4 – roflumilast cream is in phase 3 development for plaque psoriasis5 objective • to assess the short-term safety and efficacy of once-daily (qd) topical roflumilast cream in patients with mild to moderate atopic dermatitis methods • randomized, double-blind, vehicle-controlled, multicenter phase 2 study (clinicaltrials.gov nct03916081; figure 1) • at the early timepoint of 4 weeks, roflumilast cream improved severity of atopic dermatitis as measured by absolute change from baseline in eczema area and severity index (easi), yet was not statistically significant (figure 2) • a robust response to vehicle was observed • patient cases illustrating improvement in severity of atopic dermatitis with roflumilast cream are shown in figure 5 conclusions • in this small proof-of-concept study, roflumilast cream qd demonstrated efficacy compared with vehicle cream in atopic dermatitis – primary endpoint showed a trend toward, but did not reach, statistical significance – statistical significance was reached for other efficacy endpoints – substantial efficacy noted, with 72.3% easi improvement and >50% of patients achieving “clear” or “almost clear” skin on viga-ad at week 4 for roflumilast cream 0.15% – continued efficacy through week 4 was observed – high response rate with cream vehicle in this study may have been a factor in not reaching statistical significance in the primary endpoint • roflumilast cream was well-tolerated, with a low rate of application site reactions and no signs of local irritation • secondary and exploratory endpoints showed significant improvement with roflumilast cream over vehicle at week 4 (figure 3) • efficacy of roflumilast cream continued to improve through week 4 (figure 4) safety and tolerability • treatment-emergent adverse events (teaes) were uncommon in this study (table 2) • safety and tolerability of roflumilast was similar to vehicle group • all teaes were mild or moderate • low rates of application-site adverse events • no psychiatric teaes • no unintentional weight loss of more than 5% statistical analysis • the primary endpoint was analyzed with a mixed-effects model for repeated measures, as were other continuous endpoints • categorical endpoints were analyzed with a cochran-mantel-haenszel test • comparisons were specified at the 0.05 level and were not adjusted for multiplicity results • overall, patients were recruited from 3 sites in canada and 19 sites in the united states and randomized to roflumilast 0.15% (n=45), roflumilast 0.05% (n=46), or vehicle (n=45) • completion rate was over 90% in all treatment groups • baseline characteristics are presented in table 1 table 1. baseline characteristics roflumilast 0.15% (n=45) roflumilast 0.05% (n=46) vehicle (n=45) age, mean (sd), years 38.0 (16.5) 44.3 (17.0) 42.4 (17.6) sex, female, n (%) 33 (73.3) 31 (67.4) 29 (64.4) race, n (%) white 24 (53.3) 32 (69.6) 32 (71.1) black 14 (31.1) 11 (23.9) 11 (24.4) multiple/other 7 (15.6) 3 (6.5) 2 (4.4) viga-ad score, mean (sd) 2.8 (0.4) 2.8 (0.4) 2.8 (0.4) 2 (mild), n (%) 10 (22.2) 11 (23.9) 9 (20.0) 3 (moderate), n (%) 35 (77.8) 35 (76.1) 36 (80.0) easi, mean score (sd) 9.5 (4.1) 8.4 (4.1) 9.2 (3.9) bsa, mean (sd), % 9.6 (6.0) 8.4 (7.1) 10.5 (6.6) wi-nrs, mean score (sd) 6.6 (2.0) 6.5 (2.0) 7.2 (2.1) wi-nrs score ≥6, n (%) 32 (71.1) 31 (67.4) 38 (84.4) data are presented for safety population. bsa: body surface area; easi: eczema area and severity index; sd: standard deviation; viga-ad: validated investigator global assessment for atopic dermatitis; wi-nrs: worst itch numeric rating scale. roflumilast cream, a potent pde-4 inhibitor, represents a potential effective qd topical treatment for atopic dermatitis. favorable safety profile and encouraging efficacy results warrant further investigation of roflumilast cream in larger studies over longer times figure 1. study design bsa: body surface area; easi: eczema area and severity index; qd: once daily; viga-ad: validated investigator global assessment for atopic dermatitis; wi-nrs: worst itch numeric rating scale. vehicleroflumilast 0.15% baseline week 4 viga-ad = 3 viga-ad = 2 easi cfb = -77% viga-ad = 3 viga-ad = 3 easi cfb = -27% references 1. silverberg ji, et al. j dermatolog treat 2016;27:568-576. 2. bäumer w, et al. inflamm allergy drug targets 2007;6:17-26. 3. guttman-yassky e, et al. exp dermatol 2019;28:3-10. 4. dong c, et al. j pharmacol exp ther 2016;358:413-422. 5. lebwohl mg, et al. n engl j med 2020;383:229-239. acknowledgements • this study was supported by arcutis biotherapeutics, inc. • thank you to the investigators and their staff for their participation in the trial • we are grateful to the study participants and their families for their time and commitment • writing support was provided by aleksandra adomas, phd, cmpp, touch scientific, philadelphia, pa, and funded by arcutis biotherapeutics, inc. disclosures mjg, lhk, mz, ml, sek, zdd, lf, tmj, es-cp, rb, nb, stg, and rak: investigator, consultant, and/or advisory board member for arcutis biotherapeutics, inc. zdd has received grant support from arcutis biotherapeutics, inc. hw has a patent application relevant to this work. cm, me, ln, rch, mg, and drb: employees of arcutis biotherapeutics, inc. table 2. summary of aes teae, n (%) roflumilast 0.15% (n=45) roflumilast 0.05% (n=46) vehicle (n=45) patients with any teae 12 (26.7) 10 (21.7) 6 (13.3) any treatment-related teae 0 2 (4.3) 2 (4.4) teae leading to study discontinuationa 0 1 (2.2) 1 (2.2) saeb 0 1 (2.2) 0 maximum severity of teaes mild 10 (22.2) 6 (13.0) 5 (11.1) moderate 2 (4.4) 4 (8.7) 1 (2.2) application site teaes application site pain 0 1 (2.2) 1 (2.2) atopic dermatitis worsening 0 0 1 (2.2) skin lacerationc 0 1 (2.2) 0 aroflumilast 0.05%: moderate application site pain; vehicle: moderate worsening of ad. broflumilast 0.05%: mild traumatic spinal cord compression that was considered unrelated to the study drug. cunrelated to the study drug. data presented for safety population. ae: adverse event; sae: serious adverse event; teae: treatment-emergent adverse event. figure 5. patient cases representative of the efficacy of roflumilast cream 0.15% at week 4 compared with vehicle cfb: change from baseline; easi: eczema area and severity index; viga-ad: validated investigator global assessment for atopic dermatitis. week 1 week 2 week 4 ls m ea n ch an ge f ro m b as el in e, % (9 5% c i) (a) 0 -10 -20 -30 -40 -50 -60 -70 -80 -90 p=0.040 p=0.035 vehicle (n=45)roflumilast 0.15% (n=45) roflumilast 0.05% (n=46) melinda j. gooderham,1 leon h. kircik,2 matthew zirwas,3 mark lee,4 steven e. kempers,5 zoe d. draelos,6 laura ferris,7 terry m. jones,8 etienne saint-cyr proulx,9 robert bissonnette,9 neal bhatia,10 scott t. guenthner,11 robert a. koppel,12 howard welgus,13 charlotte merritt,13 meg elias,13 lynn navale,13 robert c. higham,13 michael droege,13 david r. berk13 1skin centre for dermatology, probity medical research and queen’s university, peterborough, on, canada; 2icahn school of medicine at mount sinai, ny, indiana medical center, indianapolis, in, physicians skin care, pllc, louisville, ky, and skin sciences, pllc, louisville, ky, usa; 3dermatologists of the central states, probity medical research, and ohio university, bexley, oh, usa; 4progressive clinical research, san antonio, tx, usa; 5minnesota clinical study center, fridley, mn, usa; 6dermatology consulting services, pllc, high point, nc, usa; 7university of pittsburgh, department of dermatology, pittsburgh, pa, usa; 8us dermatology partners, bryan, tx, usa; 9innovaderm research, montreal, qc, canada; 10therapeutics clinical research, san diego, ca, usa; 11the indiana clinical trials center, pc, plainfield, in, usa; 12clinical trials management, llc, metairie, la, and tulane university school of medicine in new orleans, la, usa; 13arcutis biotherapeutics, inc., westlake village, ca, usa the safety and efficacy of roflumilast cream 0.15% and 0.05% in atopic dermatitis: phase 2 proof-of-concept study roflumilast cream 0.15% qd roflumilast cream 0.05% qd vehicle qd endpoints • primary: easi change from baseline • secondary: – easi % change from baseline – easi-50 and easi-75 – bsa – wi-nrs • exploratory: – viga-ad “clear” or “almost clear” – viga-ad “clear” or “almost clear” + ≥2-grade improvement • safety and tolerability 4 weeks ra nd om iz at io n 1:1:1 n=136 eligibility • mild or moderate atopic dermatitis (viga-ad=2 or 3) • age ≥12 years • 1.5-35% bsa • easi >5 vehicle (n=45)roflumilast 0.15% (n=45) roflumilast 0.05% (n=46) week 4 pa ti en ts , % (9 5% c i) 100 90 80 70 60 50 40 20 10 0 30 52.3 59.1 31.1 p=0.009 p=0.045 week 4 ls m ea n ch an ge f ro m b as el in e, % (9 5% c i) -72.3 -69.4 -55.8 p=0.049 0 -10 -20 -30 -40 -50 -60 -70 -80 -90 easi-75 responder rate viga-ad score of “clear” or “almost clear” (a) (b) (c) week 4 pa ti en ts , % (9 5% c i) 52.3 50.0 31.1 p=0.040 100 90 80 70 60 50 40 20 10 0 30 easi percent change from baseline p=0.049 scan qr code for a digital copy of this poster vehicle (n=45)roflumilast 0.15% (n=45) roflumilast 0.05% (n=46) -6.4 -6.0 -4.8 -8 -7 -6 -5 -4 -3 -2 -1 0 week 4 ls m ea n ch an ge f ro m b as el in e (9 5% c i) p=0.356 p=0.097 slide number 1 << /ascii85encodepages false /allowpsxobjects false /allowtransparency false /alwaysembed [ true ] /antialiascolorimages false 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false /pdfxoutputcondition () /pdfxoutputconditionidentifier (cgats tr 001) /pdfxoutputintentprofile (u.s. web coated \050swop\051 v2) /pdfxregistryname (http://www.color.org) /pdfxsetbleedboxtomediabox false /pdfxtrapped /false /pdfxtrimboxtomediaboxoffset [ 0 0 0 0 ] /parsedsccomments true /parsedsccommentsfordocinfo true /parseiccprofilesincomments true /passthroughjpegimages true /preservecopypage true /preservedicmykvalues true /preserveepsinfo true /preserveflatness false /preservehalftoneinfo false /preserveopicomments false /preserveoverprintsettings true /startpage 1 /subsetfonts true /transferfunctioninfo /apply /ucrandbginfo /remove /useprologue false /srgbprofile (srgb iec61966-2.1) >> setdistillerparams << /hwresolution [2400 2400] /pagesize [612.000 792.000] >> setpagedevice poster presented at the annual winter clinical dermatology conference; january 18-23, 2019; kauai, hi variables affecting delivery of glycopyrronium tosylate through human skin in vitro franceso caserta1, jon lenn1, hans hofland2 1medpharm, durham, nc; 2dermira, inc., menlo park, ca introduction • hyperhidrosis is a medical condition characterized by excessive sweating beyond what is required for normal thermal regulation, and can involve multiple body areas including the axillae, palms, soles, or craniofacial regions1 • glycopyrronium tosylate (gt) is a topical anticholinergic recently approved by the us food and drug administration for the treatment of primary axillary hyperhidrosis in patients ≥9 years (glycopyrronium cloth, 2.4%, for topical use)2 • in vitro permeation models can be a powerful tool to gain insight into drug absorption (flux) profiles under varying conditions and to optimize clinical trial design3 objective • to determine using in vitro skin penetration studies how gt delivery through human skin is impacted by varying conditions including occlusion, wash-off, and skin thickness methods • across all experiments: – human skin was dermatomed to a thickness of approximately 0.5 mm and mounted into flow-through diffusion cells (medflux-ht®) – gt solution was applied at 10mg/cm2 and allowed to dry occlusion • human abdominal skin was obtained from 3 donors after abdominoplasty • two methods of occlusion were used: 1) parafilm was pressed on the surface for the donor compartment, which leaves a small closed-off column of air above the skin; 2) saran wrap was pressed down on top of the surface of the skin • non-occluded skin was used as control • the receiving fluid was collected over 12 hours, and the gt flux was assessed using liquid chromatography with tandem mass spectrometry (lc/ms/ms) wash-off • human abdominal skin was obtained from 3 donors after abdominoplasty • after drying, gt was removed from the skin by wiping the skin surface once with the following: 1) a dry cotton swab; 2) a cotton swab dipped in one of the six washing solutions; 3) a cotton swab dipped in warm water • six washing solutions were used: 1) “hand soap” = 0.5% dial gold in warm water; 2) “bar soap” = 5% dove white bar soap in warm water; 3) “dish soap” = 5% dawn original in warm water; 4) “germ-x” = 70% ethanol hand sanitizer; 5) 70% ipa = rubbing alcohol; 6) warm water. • to assess the amount of gt left on the surface of the skin after this washing procedure, the surface of the skin was wiped with 1) dry cotton swab, 2) cotton swab immersed in ethanol:water (9:1), 3) dry cotton swab, followed by 4) one tape strip. these three cotton swabs and one tape strip were combined and assayed for gt by lc/ms/ms • the amount of gt in the stratum corneum was assessed by tape stripping 5 times (d-squame tape), and tapes were combined and assayed for gt exposure time • human abdominal skin was obtained from 4 donors after abdominoplasty • after application, gt was left on the skin for 5, 15, or 60 minutes before using the “hand soap” method to remove gt from the skin surface • during this exposure period the skin was either occluded using the saran wrap method or not occluded • not-occluded and not-washed off skin served as control skin thickness • human skin from 4 anatomical sites (abdominal [control], axillary, palmar, and plantar skin) was obtained from 3 donor/cadavers • the receiving fluid was collected over 12 hours, and the gt flux was assessed using lc/ms/ms results occlusion • occlusion increased skin flux 7-10 fold, independent of donor to donor differences and independent of the occlusion method used (figure 1) figure 1. the effect of occlusion on steady state flux of glycopyrronium tosylate through human skin not occluded parafilm occluded saran wrap occluded donor 1 donor 2 donor 3 10,000 1,000 100 10 1g ly co py rr on iu m t os yl at e a bs or pt io n (n g/ cm 2 /h ) each bar represents the mean and standard error of 4 replicates per donor results wash-off and exposure time • all wash-off techniques were effective; however, washing with hand soap was the most effective method (99.5% removal of gt from skin surface) while use of water alone was the least effective method (96.2% removal; figure 2) • it is expected that in a real-life situation washing gt off the skin will be even more effective when using running water and rubbing hands for several seconds figure 2. the effectiveness of various wash-off methods on glycopyrronium tosylate from human skin stratum corneum surface source wash method 70% ipa bar soap dish soap germ-x hand soap warm water 0 1 2 3 % r em ai ni ng each bar represents the mean and standard error of 4 replicates per donor • the amount of gt delivered through human skin was reduced by 90% after washing. this reduction appeared independent of the length of time the product was left on the skin before washing. however, in one of the 4 donors (donor 2) there appeared to be a benefit of leaving the product on the skin before washing (figure 3) • occlusion for as short as 5 minutes restored the gt flux to approximately control levels (i.e., not washed off, not occluded). longer occlusion does not appear to increase the flux beyond control levels (i.e., not washed off, not occluded) (figure 3) figure 3. the effect of exposure time and occlusion on glycopyrronium tosylate delivery through human skin not occluded, not washed off not occluded, washoff after 5 minutes not occluded, washoff after 15 minutes not occluded, washoff after 60 minutes occluded, washoff after 5 minutes occluded, washoff after 15 minutes occluded, washoff after 60 minutes donor 1 donor 2 donor 3 donor 4 1 g ly co py rr on iu m t os yl at e a bs or pt io n (n g/ cm 2 /h ) 1,000 100 10 each bar represents the mean and standard error of 4 replicates per donor results skin thickness / anatomical sites • on average 30 to 40-fold less gt delivery was observed through palmar skin vs axillary skin (figure 4) • variability was observed within and between donor results, though in general, similar delivery of gt was observed through axillary vs abdominal skin and for palmar vs plantar skin (for 2 to 3 donors) figure 4. the effect of skin thickness on steady state flux of glycopyrronium tosylate through human skin obtained from various anatomical sites, including palmar, plantar, axillary and abdominal skin palmar plantar axillary abdominal donor 1 donor 2 donor 3 0.01 g ly co py rr on iu m t os yl at e a bs or pt io n (n g/ cm 2 /h ) 1,000 100 10 1 0.1 each bar represents the mean and standard error of 4 replicates per donor; absorption not detected for plantar sample from donor 3 conclusions • in these in vitro studies, wash-off, occlusion and skin thickness substantially influenced gt delivery – occlusion increased gt steady state flux by 7-10 fold – all wash-off methods worked well and were able to remove up to 99.5% surface gt (0.5% hand soap in water) – a 90% decrease in flux was observed after washing, independent of how long gt was left on the skin (5, 15, or 60 min) – occlusion for as short as 5 minutes was able to restore the flux to levels found in control group (not washed off, not occluded) – longer occlusion (up to 60 min) did not increase the flux above control group – gt delivery through palmar and plantar skin is 30-40 fold lower compared to delivery through axillary or abdominal skin – gt delivery through axillary and abdominal skin is similar • it should be noted that the in vitro skin penetration studies summarized here involved a single dose of gt; skin penetration of gt upon chronic application was not assessed in these studies • these data underscore the importance of characterizing skin flux under clinical conditions and will inform future hyperhidrosis clinical trial designs with topical agents references 1. doolittle et al. arch dermatol res. 2016;308(10):743-9. 2. qbrexzatm (glycopyrronium) cloth [prescribing information]. dermira, inc., menlo park, ca. 2018. 3. abd et al. skin models for the testing of transdermal drugs. clin pharmacol. 2016;8:163–176. acknowledgements this study was funded by dermira, inc. all costs associated with development of this poster were funded by dermira, inc. author disclosures fc & jh: employees of medpharm hh: employee of dermira, inc. powerpoint presentation efficacy of ixekizumab in patients previously treated with il-17 inhibitors fall clinical dermatology conference 37th anniversary (fallcdc); las vegas, nv, usa; october 18-21, 2018 study was sponsored by eli lilly and company background  previous use of biologics may detrimentally impact the efficacy of subsequent biologic therapies1,2  ixekizumab is a high-affinity monoclonal antibody that selectively targets il-17a3 − is approved for treating moderate-to-severe plaque psoriasis objective  to evaluate the impact of previous use of biologics, particularly those targeting the il-17 pathway (brodalumab [il-17ra antagonist] or secukinumab [il-17a antagonist]), on the 52-week efficacy of ixekizumab (il-17a antagonist) in patients with moderate-to-severe psoriasis methods pasi 75 response at week 52 by previous il-17 inhibitor exposure nri, blinded treatment dosing period, itt population conclusions  previous exposure to biologics, including those targeting the il-17 pathway (brodalumab or secukinumab), did not impact the 52-week efficacy of ixekizumab key results references 1. ruiz salas v, et al. j eur acad dermatol venereol. 2012;26:508-513. 2. mazzotta a, et al. am j clin dermatol. 2009; 10:319-324. 3. liu l, et al. j inflamm res. 2016;9:39-50. baseline demographics and disease characteristics by previous il-17 inhibitor exposure privacy notice regarding the collection of personal information by scanning this qr code, you are consenting to have your ip address and, if you choose, email address temporarily retained in a secured computer system and used only for counting purposes, performing file download, and sending you an email. your information will not be shared for any other purpose, unless required by law. you will not receive any future communications from eli lilly and company based on the system-retained information. contact information at: http://www.lilly.com/pages/contact.aspx disclosures  k. a. papp has served as a speaker, advisor, and/or received grant/research support from: 3m, abbott/abbvie, akesis, akros, allergan, alza, amgen, anacor, applied molecular evolution, astellas, baxter, bayer, boehringer ingelheim, celgene, celtic, centocor, cipher, coherus, dermira, dow pharma, eli lilly and company, forward pharma, funxional therapeutics, galderma, genentech, glaxosmithkline, isotechnika, janssen, janssen biotech (centocor), johnson & johnson, kyowa hakko kirin, leo pharma, lypanosys, medimmune, meiji seika pharma, merck, merck serono, mitsibushi pharma, mylan, novartis, pangenetics, pfizer, regeneron pharmaceuticals, roche, stiefel, sosei, takeda, ucb, vertex, wyeth, and xoma  this study was sponsored by eli lilly and company. medical writing assistance was provided by luke carey, phd, of proscribe – part of the envision pharma group, and was funded by eli lilly and companysafety overview by previous il-17 inhibitor exposure blinded treatment dosing period, safety population kim a. papp,1 andrew blauvelt,2 john sullivan,3 paula polzer,4 lu zhang,4 chih-ho hong5 1probity medical research, waterloo, canada; 2oregon medical research center, portland, usa; 3kingsway dermatology & aesthetics, miranda, australia; 4eli lilly and company, indianapolis, usa; 5probity medical research, surrey, canada il-17=interleukin-17; il-17ra=interleukin-17 receptor a study design ixora-p a dose-adjustment (ixe q4w to ixe q2w) based on whether a patient achieved spga ≥2 at 2 consecutive visits during week 12 through week 40; investigators were blinded to the predefined criteria and timing ixe=ixekizumab; ixe q4w=80 mg ixe every 4 weeks; ixe q2w=80 mg ixe every 2 weeks; ixe q4w/ixe q2w dose adjustment=80 mg ixe every 4 weeks/every 2 weeks; r=randomization; spga=static physician’s global assessment; w=week r blinded treatment dosing period ixe q2w (n=611) 1227 patients randomized 2:1:1 160-mg ixe starting dose w0 w16 w52w40w20 w24 w32w28 w36 dose-adjustment per protocola ixe q4w/ixe q2w (n=306) ixe q4w (n=310) follow upscreening ae=adverse event; il-17=interleukin-17; ixe q2w=80 mg ixekizumab every 2 weeks; ixe q4w=80 mg ixekizumab every 4 weeks; sae=serious adverse event; teae=treatment-emergent adverse event data are mean (standard deviation) unless otherwise stated bsa=body surface area; il-17=interleukin-17; pasi=psoriasis area and severity index il-17 inhibitor naïve (n=939) il-17 inhibitor experienced (n=288) age, years 48.1 (13.6) 46.6 (13.1) male, n (%) 609 (64.9) 201 (59.8) weight, kg 91.1 (23.7) 89.9 (22.5) psoriasis duration, years 18.5 (12.5) 22.2 (12.9) percentage of bsa involved 26.1 (17.4) 27.5 (18.0) previous biologic therapy, n (%) 284 (30.2) 288 (100.0) used 1 186 (19.8) 197 (68.4) used 2 58 (6.2) 62 (21.5) used ≥3 40 (4.3) 29 (10.1) previous secukinumab therapy, n (%) 0 13 (4.5) previous brodalumab therapy, n (%) 0 277 (96.2) pasi 20.1 (8.0) 21.2 (9.0) * * p<.05 vs. ixe q4w (fisher’s exact test) ci=confidence interval; il-17=interleukin-17; itt=intent-to-treat; ixe q2w=80 mg ixekizumab every 2 weeks; ixe q4w=80 mg ixekizumab every 4 weeks; nri=non-responder imputation; pasi=psoriasis area and severity index  ixekizumab showed efficacy in patients regardless of previous exposure to an il-17 inhibitor biologic pasi 90 response at week 52 by previous il-17 inhibitor exposure nri, blinded treatment dosing period, itt population * ‡† 80 45 42 51 47 61 58 66 64 75 73 79 81 76 82 86 85 87 † † * p<.05 vs. ixe q4w; † p<.01 vs. ixe q4w; ‡ p<.001 vs. ixe q4w (fisher’s exact test) ci=confidence interval; il-17=interleukin-17; itt=intent-to-treat; ixe q2w=80 mg ixekizumab every 2 weeks; ixe q4w=80 mg ixekizumab every 4 weeks; nri=non-responder imputation; pasi=psoriasis area and severity index  ixekizumab showed efficacy in patients regardless of previous exposure to a biologic pasi responses at week 52 by previous biologic exposure nri, blinded treatment dosing period, itt population * p<.05 vs. ixe q4w; ‡ p<.001 vs. ixe q4w (fisher’s exact test) ci=confidence interval; il-17=interleukin-17; itt=intent-to-treat; ixe q2w=80 mg ixekizumab every 2 weeks; ixe q4w=80 mg ixekizumab every 4 weeks; nri=non-responder imputation; pasi=psoriasis area and severity index pasi 100 response at week 52 by previous il-17 inhibitor exposure nri, blinded treatment dosing period, itt population * p<.05 vs. ixe q4w; ‡ p<.001 vs. ixe q4w (fisher’s exact test) ci=confidence interval; il-17=interleukin-17; itt=intent-to-treat; ixe q2w=80 mg ixekizumab every 2 weeks; ixe q4w=80 mg ixekizumab every 4 weeks; nri=non-responder imputation; pasi=psoriasis area and severity index n (%) ixe q4w ixe q2w naïve (n=243) experienced (n=67) naïve (n=233) experienced (n=73) naïve (n=461) experienced (n=148) ≥1 teae 202 (83.1) 45 (67.2) 180 (77.3) 50 (68.5) 346 (75.1) 201 (69.8) death 1 (0.4) 0 0 0 2 (0.4) 0 ≥1 sae 13 (5.3) 3 (4.5) 12 (5.2) 4 (5.5) 25 (5.4) 7 (4.7) discontinuation due to ae 5 (2.1) 1 (1.5) 10 (4.3) 3 (4.1) 13 (3.0) 5 (3.4) infections 135 (55.6) 31 (46.3) 120 (51.5) 30 (41.1) 211 (45.8) 67 (45.3) injection-site reactions 27 (11.1) 4 (6.0) 15 (6.4) 3 (4.1) 66 (14.3) 12 (8.1) allergic reactions/hypersensitivities 24 (9.9) 4 (6.0) 22 (9.4) 3 (4.1) 53 (11.5) 6 (4.1) depressions 4 (1.6) 1 (1.5) 3 (1.3) 1 (1.4) 8 (1.7) 4 (2.7) cerebrocardiovascular events 2 (0.8) 1 (1.5) 2 (0.9) 0 9 (0.2) 0 inflammatory bowel disease 1 (0.4) 0 1 (0.4) 0 3 (0.7) 1 (0.7) malignancies 2 (0.8) 0 5 (2.1) 1 (1.4) 0 2 (1.4) ixe q4w/ ixe q2w slide number 1 skin july 2021 1199 proof returned skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 359 original research tele-dermatology recruitment during covid-19: an application of behavioral economic principles morgan chambers, bs1, jeffrey miller, md, mba1, bruce brod, md, mhci, faad2, jordan lim, mb bch, bao1 1penn state college of medicine, hershey, pa 2 university of pennsylvania perelman school of medicine, department of dermatology philadelphia, pa amidst the recent covid-19 epidemic in the united states (us), our healthcare system innovated rapidly to meet challenges. to provide patient care during this time, we transitioned to the use of tele-dermatology for acute and chronic management. one initial problem we faced was decreased patient uptake. many potential factors influence patient choice to use tele-dermatology including convenience, technological comfortability, confidence in diagnostic accuracy, and lack of physical contact.1 to help overcome these barriers, we designed and implemented an intervention using behavioral economics, which is based on the premise that people predictably behave irrationally, leading to decision errors. choice architecture, coined by behavioral economists thaler and sunstein in 2008, refers to the way choices are presented, ultimately impacting decisions.2 it involves using techniques to influence consumer choice, such as the use of defaults, similar to the process of organ donation. america and certain countries in europe require people to “sign-up” for organ donation leading to low participation. in the netherlands, minimal participation is noted as people must actively abstract in the ever-changing state of healthcare during the recent covid-19 pandemic, our system has innovated rapidly using tele-dermatology in acute and chronic patient management. to combat barriers such as low patient enrollment, behavioral economics theories were implemented. underlying principles in choice architecture, include choice inertia, the way in which humans favor the status quo; and choice overload, where humans fail to make an optimal choice when presented with multiple options. using these theories, we modified support-staff scripts in our dermatology clinic used when rescheduling appointments. our baseline script group allowed for patients to choose from a list of options whereas our improvement script applied behavioral economic principles and used teledermatology as the default. this quality improvement initiative was employed with the hypothesis that the “improvement” group would lead to an increase in tele-dermatology enrollment over an 8-week period. our results showed the odds of patients accepting tele-dermatology were statistically significantly higher among those with script 2, compared with script 1. this also demonstrated clinical significance for our institution, showing the effect behavioral economics has on patient enrollment in tele-dermatology, which will serve as an asset during the covid-19 pandemic and beyond. limitations include small sample size, single institution, and two behavioral economic strategies were assessed in combination. introduction skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 360 choose to donate. belgium, by contrast, has a participation rate of 98% as patients must actively opt out.4 other principles of behavioral economics include status quo bias and choice overload. status quo bias theorizes that humans tend to favor the status quo rather than making a change.3 in parallel, when a person is faced with multiple options, the complexity of evaluating these options leads to “choice paralysis,” a state where no choice or suboptimal choice is made. this can be likened to the many psoriasis medications on the market; in that due to the overload of options, the dermatologist chooses to use a familiar, but less safe and effective medication. providing fewer choices to the dermatologist is an intervention that might encourage the use of biologics. we hypothesized that the use of behavioral economic principles in scripted messages by our schedulers over an 8-week period would simplify scheduling options while increasing tele-dermatology uptake by patients when designated as the default option. methods this quality improvement initiative involved a single improvement cycle, which included two groups of patients. our “baseline” group listed rescheduling options for patients and allowed them to choose, a clear example of choice overload. our “improvement” group applied behavioral economics principles previously discussed. we made signing up for tele-dermatology appointments the default option, limiting choice overload and transitioning tele-dermatology to an opt-out model. between march 6th and may 7th, 2020, a total of 225 calls were made with script #1 (control/opt-in) and a total of 267 calls were made with script #2 (behavioral economics/opt-out) by the office staff. for script #1, 33 patients chose tele-dermatology appointments (14.6%), 118 chose to reschedule (52.4%), and 74 fell in the “other” category (32.9%). for script #2, 61 patients accepted tele-dermatology appointments (22.8%), 115 patients opted-out and chose to reschedule (43.1%), and 91 fell into the “other” category (34%) (figure 1). the “other” category consisted of calls to out of service numbers, voicemails reached, and unavailable voicemails. an f-test was performed between scripts for each category to determine variance which was equal for tele-dermatology and rescheduled patients, but unequal for “other”. this was then used for subsequent t-tests that revealed no statistical differences in tele-dermatology, rescheduled, or other patients for script 1 vs. 2 (p-values of 0.30, 0.78, and 0.62, respectively). odds ratio was then calculated which showed that the odds of patients accepting tele-dermatology were higher among those with script 2, compared to those with script 1 (or = 1.90, 95% ci = 1.16, 3.11). behavioral economics diverges from traditional economic principles to incorporate insights of human nature and psychology to model how people truly behave when making a choice. in this small, randomized controlled trial, our implementation of behavioral economic principles almost doubled our patient uptake of tele-dermatology results discussion skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 361 figure 1: overall tele-dermatology data. total number of calls made for baseline script and intervention script are shown along with the number of patients who either chose tele-dermatology, to reschedule, or fell into the “other” category. appointments, which was reflected by the statistically significant odds ratio of 1.90. we speculate that these results demonstrate modifications in the intervention group’s script had a clinically significant effect on our patients’ enrollment in tele-dermatology during the covid-19 pandemic. the application of behavioral economics, being relatively new to healthcare, has been rarely reported in dermatology. various published examples in dermatology include the use of framing effects and status quo when discussing actinic keratosis treatment5, tanning practices in adolescents6, and sun protection practices7. even further, the use of social norming has been demonstrated by albertini et al. who compared average layers amongst mohs surgeons across the us, and heuristics centered-on reference dependence have been used to promote willingness to use injectable biologics in psoriasis patients.8,9 while it is becoming increasingly recognized to facilitate high value care, most health systems have not developed the capacity for widescale implementation. at the core of behavioral economics is light paternalism, a more ethical approach for influencing decision-making than mandating a choice. rather, it points people in a direction while offering the option of opting out should they have strong preferences. limitations of this study include completion at a single academic institution, limiting the ability to comment on generalizability, particularly in private practice settings. duration was limited, subsequently limiting sample size, due to clear advantages being recognized by our intervention. support staff delivering the scripts were unblinded and could have influenced the patients in other ways which we cannot appreciate in the collection of data. finally, two behavioral economic principles were combined in one arm of the study rather than having two distinct arms making it difficult to determine if one principle was more effective. total calls telederm rescheduled other script #1 225 33 118 74 script #2 267 61 115 91 0 50 100 150 200 250 300 n um be r of p at ie nt s conclusion skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 362 our clinic has implemented these interventions to nudge our patients towards adoption of tele-dermatology to provide care access and continuity. having appropriate patients seen via tele-dermatology limits the anxiety of covid-19 exposure as well as anxiety associated with an unaddressed dermatologic concern, prevents patients from seeking care in the ed, and limits use of personal protective equipment. not only does this process increase access to health care during covid-19, but its benefits can be expected to extend far beyond the pandemic. increasing tele-dermatology opportunities could potentially decrease clinic wait time, allow for more efficient triaging, and lead to less in-person traffic upon reopening. these factors will all serve as assets to providers and patients as we navigate through this evolving health care landscape. conflict of interest disclosures: none funding: none corresponding author: jordan lim, mb bch bao department of dermatology penn state hershey medical center 500 university dr hershey, pa 17033 phone: 717-531-6820 fax: 717-531-4702 email: jlim1@pennstatehealth.psu.edu references: 1. demiris g, speedie sm, hicks ll. assessment of patients' acceptance of and satisfaction with teledermatology. journal of medical systems. 2004 dec 1;28(6):575-9. 2. thaler rh, sunstein cr. nudge: improving decisions about health, wealth, and happiness. penguin; 2009. 3. samuelson w, zeckhauser r. status quo bias in decision making. journal of risk and uncertainty. 1988 mar 1;1(1):7-59. 4. emanuel ej, ubel pa, kessler jb, meyer g, muller rw, navathe as, patel p, pearl r, rosenthal mb, sacks l, sen ap. using behavioral economics to design physician incentives that deliver high-value care. annals of internal medicine. 2016 jan 19;164(2):114-9. 5. berry k, butt m, kirby js. influence of information framing on patient decisions to treat actinic keratosis. jama dermatology. 2017 may 1;153(5):421-6. 6. garc√≠a-romero mt, geller ac, kawachi i. using behavioral economics to promote healthy behavior toward sun exposure in adolescents and young adults. preventive medicine. 2015 dec 1;81:184-8. 7. o'keefe dj, wu d. gain-framed messages do not motivate sun protection: a meta-analytic review of randomized trials comparing gain-framed and loss-framed appeals for promoting skin cancer prevention. international journal of environmental research and public health. 2012 jun;9(6):212133. 8. albertini jg, wang p, fahim c, hutfless s, stasko t, vidimos at, leshin b, billingsley em, coldiron bm, bennett rg, marks vj. evaluation of a peerto-peer data transparency intervention for mohs micrographic surgery overuse. jama dermatology. 2019 aug 1;155(8):906-13. 9. oussedik e, cardwell la, patel nu, onikoyi o, feldman sr. an anchoring-based intervention to increase patient willingness to use injectable medication in psoriasis. jama dermatology. 2017 sep 1;153(9):9 skin may 2018 volume 2 issue 3 copyright 2018 the national society for cutaneous medicine 168 opinion piece editorial: overcoming consumer challenges in sunscreen selection alex m. glazer md a , ryan m. svoboda md ms b , rebeca w. teplitz ba c , darrell s. rigel md ms d a division of dermatology, university of arizona school of medicine, tucson, az b national society for cutaneous medicine, new york, ny c new york institute of technology, college of osteopathic medicine, old westbury, ny d ronald o. perelman department of dermatology, nyu school of medicine, new york, ny the advent of the internet has forever changed the face of medicine. in the modern “age of google” patient decisions are increasingly influenced by online blogs, reviews, and recommendations that include an element of subjective opinion and may not be fully based on strict scientific evidence alone. physicians who are not attuned to this will increasingly struggle when trying to provide guidance to their patients, who often have pre-conceived notions based on nonpeer reviewed information they receive on the internet. one area particularly impacted by online advice is sunscreen selection. major consumer knowledge gaps in this space accentuate this issue. for example, consumer comprehension of newly fda-mandated sunscreen labeling information is subpar, with only around 10% understanding the concepts of spf, broadspectrum, and water-resistance.1 these knowledge gaps provide an impetus for consumers to turn to external advice when choosing between sunscreen products that at first glance appear comparable. many consumers use online information to fill in these gaps—information which is often not peer-reviewed or based in rigorous science. lay sunscreen ratings frequently employ nontransparent research methods that may potentially be influenced by conflicts-ofinterest and political agendas. this problem is illustrated by the environmental working group’s (ewg) annual sunscreen guide.2 to our knowledge, the ewg’s scientific team does not include a dermatologist or photobiologist and their data appears to be largely based on hypothetical models without in vivo testing. in our opinion, their ranking system is inherently biased—focusing only half of their formula on direct sunburn prevention measures, with the rest related to potential “health hazard risks” based on unrelated science leveraged to support their views. problems related to this evaluation process have led to sunscreens historically rated highly by the ewg having significant failures leading to class-action lawsuits for non-performance.3 as an additional example of the concerning nature of the ewg’s ranking system, the rating scale significantly penalizes sunscreens that contain oxybenzone due to reported carcinogenic risks with oral ingestion in animal models. however, millions of users use oxybenzone-containing sunscreen products every summer weekend, and none of the ill skin may 2018 volume 2 issue 3 copyright 2018 the national society for cutaneous medicine 169 effects suggested by the ewg have been seen in human populations. in addition, to reach the systemic levels of oxybenzone shown to be potentially harmful in rats, a consumer would need to apply 1 mg/cm2 of sunscreen (50% of the concentration used for spf testing) to 25% of the body surface area (bsa) every day for 277 years. even if sunscreen was applied to 100% of the bsa at a density of 2 mg/cm2 (which is essentially an impossibility), it would still take approximately 35 years of daily application to approach the amount of oxybenzone that the rats were exposed to in laboratory studies.4,5 furthermore, the ewg penalizes sunscreens with an spf greater than 50 because “imbued with a false sense of security, people extend their time in the sun well past the point when users of low-spf products would head indoors.” this viewpoint fails to account for studies demonstrating that in real-world application settings, superior protection is achieved with the use of higher-spf sunscreens.6 the typical application density in real-world settings is less than half of that mandated during the spf testing process for new products; as such there are benefits to higher spf products seen in actual use that do not translate to the laboratory setting.7 lastly, although trying to position themselves as an independent auditor, there is a potential direct conflict-of-interest between the ewg and their recommendations as they earn clickthrough revenue through purchase of recommended products at online stores. other online sunscreen ratings have similar limitations.8 despite this, these problematic statements often get disseminated by other publications without appropriate scrutiny, which in our opinion may be potentially increasing public risk.9 with these types of challenges, how can we better ensure that patients are properly equipped to make informed sunscreen selections? first-and-foremost, dermatologists must do more than simply urge their patients to use sunscreen. we must be proactive and ask what our patients know about sunscreen selection, where they get their information, and which products they use. we must be aware of the resources patients are using to guide sunscreen purchases so that education can be imparted and misinformation corrected. dermatologists also must keep current with the evolving science of sunscreen evaluation. the fda has made efforts to make sunscreen labeling more useful to the general consumer, but these have been largely unsuccessful.1 part of the problem is that spf only uses an indirect protection measure (sunburn) that does not relate directly to the carcinogenic properties of ultraviolet radiation. in an attempt to improve this, research targeted at developing efficacy measures more directly related to the cancer-protective mechanisms of sunscreen is underway.10-13 multiple studies have demonstrated that the regular use of sunscreen decreases skin cancer risk.14-16 even with a minor improvement in sunscreen use, it has been estimated that 230,000 cases of invasive melanoma could be prevented in the us over the next 15 years.17 despite an apparently easy opportunity for primary prevention, an abundance of internet information may be discouraging people from appropriate sunscreen usage, thereby exposing them to undue risk. by producing a more comprehensible framework that allows product comparison based on efficiency in preventing skin cancer, the potentially negative effect of recommendations from nonpeer reviewed sources could be eliminated. in any event, dermatologists must be at the forefront of the effort to abolish the impact of skin may 2018 volume 2 issue 3 copyright 2018 the national society for cutaneous medicine 170 misleading internet “science” in order to best protect our patients in this area. conflict of interest disclosures: dr. rigel serves as a consultant for johnson & johnson consumer inc., beiersdorf, and proctor & gamble. funding: none corresponding author: alex m. glazer, md department of dermatology, university of arizona po box 245024 1515 n. campbell avenue tucson, az 85724-5024 212-685-3252 (office) alexglazer@gmail.com references: 1. svoboda rm, teplitz rw, farberg as, rigel ds. patient and consumer knowledge of sunscreen labeling terminology: a cross-sectional survey. manuscript in preparation. 2. ewg’s guide to sunscreens http://www.ewg.org/sunscreen/ accessed june 17, 2017. 3. kroll d. “the failure of jessica alba’s honest sunscreen explained”. forbes. august 3 2015. https://www.forbes.com/sites/davidk roll/2015/08/03/the-failure-ofjessica-albas-honest-companysunscreen-explained/#57c2df8d3483. accessed june 19 2017. 4. wang sq, burnett me, lim hw. safety of oxybenzone: putting numbers into perspective. arch dermatol. 2011;147(7):865-866. 5. wang sq, douza sw, lim hw. safety of retinyl palmitate in sunscreens: a critical analysis. j am acad dermatol. 2011;63(5):903-906. 6. williams jd, maitra p, atillasoy e, wu mm, farberg as, rigel ds. spf 100+ sunscreen is more protective against sunburn than spf 50+ in actual-use: results of a randomized, double-blind, split-face, natural sunlight exposure, clinical trial. j am acad dermatol. 2017. 7. ou-yang h, stanfield j, cole c, appa y, rigel d. high-spf sunscreens (spf >/= 70) may provide ultraviolet protection above minimal recommended levels by adequately compensating for lower sunscreen user application amounts. j am acad dermatol. 2012;67(6):12201227. 8. consumer reports sunscreen buying guide http://www.consumerreports.org/cro /sunscreens/buying-guide.htm accessed june 17, 2017. 9. why some people worry that sunscreen might be bad for you popular science http://www.popsci.com/sunscreenharmful accessed june 14, 2017. 10. cole c, appa y, ou-yang h. a broad spectrum high-spf photostable sunscreen with high uva-pf can protect against cellular damage at high uv exposure doses. photodermatol photoimmunol photomed. 2014;30(4):212-219. mailto:alexglazer@gmail.com skin may 2018 volume 2 issue 3 copyright 2018 the national society for cutaneous medicine 171 11. liebel f, kaur s, ruvolo e, et al. irradiation of skin with visible light induces reactive oxygen species and matrix-degrading enzymes. j invest dermatol. 2012;132(7):1901-1907. 12. seité s, moyal d, verdier mp, et al. accumulated p53 protein and uva protection level of sunscreens. photodermatol photoimmunol photomed. 2000;16(1):3-9. 13. mancuso jb, maruthi r, wang sq, et al. sunscreens: an update. am j clin dermatol. 2017; may 16. doi: 10.1007/s40257-017-0290-0. [epub ahead of print] 14. green ac, williams gm, logan v, et al. reduced melanoma after regular sunscreen use: randomized trial follow-up. j clin oncol. 2011;29(3):257-263. 15. olsen cm, wilson lf, green ac, et al. cancers in australia attributable to exposure to solar ultraviolet radiation and prevented by regular sunscreen use. aust n z j public health. 2015;39(4):471-476. 16. ghiasvand r, weiderpass e, green ac, et al. sunscreen use and subsequent melanoma risk: a population-based cohort study. j clin oncol. 2016; sep 12. doi: 10.1200/jco.2016.67.5934 [epub ahead of print] 17. olsen cm, wilson lf, green ac, biswas n, loyalka j, whiteman dc. how many melanomas might be prevented if more people applied sunscreen regularly? british j dermatol. 2018;178(1):140147. conclusions • the results of the prespecified interim analysis of patients with locally advanced cscc from this phase 2 prospective study show that treatment with cemiplimab 3 mg/kg q2w is associated with substantial activity and durable responses. the safety profile is comparable with other anti-pd-1 agents. • combined with recently published data,4 this analysis further demonstrates that advanced cscc, whether metastatic or locally advanced, is responsive to cemiplimab. background • cutaneous squamous cell carcinoma (cscc) is the second most common skin cancer, after basal cell carcinoma.1 • surgical cure rate for cscc is high in early stage disease.2 • there is no approved systemic therapy for patients with advanced cscc (locally advanced cscc that is no longer amenable to surgery or radiation therapy, or metastatic cscc). • cemiplimab (regn2810) is a high-affinity, highly potent human monoclonal antibody directed against programmed death-1 (pd-1).3,4 • cemiplimab demonstrated substantial activity and durable response with a safety profile comparable with other anti-pd-1 agents, in patients with advanced cscc from phase 1 expansion cohorts and patients with metastatic cscc from primary analysis of the phase 2 study.4 • here, we present a prespecified interim analysis of the locally advanced cscc cohort from the pivotal phase 2 study (nct02760498). objectives • the primary objective was to evaluate overall response rate according to independent central review per response evaluation criteria in solid tumors (recist) 1.15 (for scans) and modified world health organization criteria (who; for photos). • secondary objectives include: estimation of duration of response (durable disease control rate was also analyzed) assessment of safety and tolerability of cemiplimab. methods • adult patients with locally advanced cscc (without nodal or distant metastasis), who were not candidates for surgery or radiation therapy, from group 2 of the phase 2, non-randomized, global, pivotal trial of cemiplimab in patients with advanced cscc are included in this analysis (figure 1). • severity of treatment-emergent adverse events (teaes) was graded according to the national cancer institute common terminology criteria for adverse events (version 4.03). • this interim analysis was prespecified and includes patients who started study treatment at least 9 months prior to the data cut-off date (october 27, 2017). references 1. rogers hw et al. jama dermatol. 2015;151:1081–1086. 2. kauvar an et al. dermatol surg. 2015;41:1214–1240. 3. burova e et al. mol cancer ther. 2017;16:861–870. 4. migden mr and rischin d et al. n engl j med. 2018;379:341–351. 5. eisenhauer ea et al. eur j cancer. 2009;45:228–247. the locally advanced cscc cohort (group 2) of the phase 2 study is now fully enrolled; the primary analysis of the results is pending. acknowledgments we thank the patients, their families, and all investigators involved in this study. the study was funded by regeneron pharmaceuticals, inc., and sanofi. medical writing support and typesetting was provided by prime, knutsford, uk, funded by regeneron pharmaceuticals, inc., and sanofi. copies of this poster obtained through quick response (qr) code are for personal use only and may not be reproduced without permission the author of this poster. table 3. teaes regardless of attribution teaes locally advanced cscc (n=23) n (%) any grade grade ≥3 any 23 (100.0) 8 (34.8) serious 5 (21.7) 4 (17.4) led to discontinuation 1 (4.3) 1 (4.3) with an outcome of death† 2 (8.7) 2 (8.7) occurred in at least four patients‡ fatigue 9 (39.1) 1 (4.3) diarrhea 7 (30.4) 0 nausea 6 (26.1) 0 pruritus 5 (21.7) 0 hypothyroidism 5 (21.7) 0 arthralgia 4 (17.4) 1 (4.3) decreased appetite 4 (17.4) 0 dry skin 4 (17.4) 0 pneumonia 4 (17.4) 3 (13.0) †one death was considered unrelated to study treatment: the patient was hospitalized on study day 134 with pneumonia and placed on a ventilator for support. the patient was also found to have evidence of heart failure, considered secondary to septic shock. the patient was extubated and died on study day 136. details of the death that was considered related to treatment can be found in table 4. ‡events are listed as indicated on the case report form. adverse events were coded according to preferred terms (meddra version 20.0). included in this table are teaes of any grade that occurred in ≥4 patients. events are listed in decreasing order of frequency by any grade. table 4. investigator-assessed treatment-related teaes teaes locally advanced cscc (n=23) n (%) any grade grade ≥3 any 20 (87.0) 3 (13.0) serious 1 (4.3) 1 (4.3) led to discontinuation 1 (4.3) 1 (4.3) with an outcome of death† 1 (4.3) 1 (4.3) occurred in at least four patients‡ fatigue 7 (30.4) 0 nausea 5 (21.7) 0 diarrhea 4 (17.4) 0 hypothyroidism 4 (17.4) 0 †patient developed hyponatraemia on study day 13 and pneumonia on study day 14; both teaes were assessed as unrelated to treatment. the patient died on study day 24 due to unknown cause that was assessed as treatment-related. ‡events are listed as indicated on the case report form. adverse events were coded according to preferred terms (meddra version 20.0). included in this table are investigator-assessed treatment-related teaes of any grade that occurred in ≥4 patients. events are listed in decreasing order of frequency by any grade. grade ≥3 treatment-related teaes reported were dizziness (n=1) and increased aspartate aminotransferase (n=1). table 2. tumor response assessment by independent central review locally advanced cscc (n=23) best overall response, n (%) complete response 0 partial response 10 (43.5) stable disease 9 (39.1) progressive disease 2 (8.7) not evaluable† 2 (8.7) overall response rate, % (95% ci) 43.5 (23.2–65.5) durable disease control rate, % (95% ci)‡ 69.6 (47.1–86.8) median observed time to response, months (range)§ 2.8 (1.9–7.6) †includes missing and unknown tumor response. ‡defined as the proportion of patients without progressive disease for at least 105 days. §data shown are from patients with confirmed responses. ci, confidence interval. results baseline characteristics, disposition, and treatment exposure • as of the data cut-off date, 23 patients were eligible for inclusion in this analysis (table 1). thirteen patients (56.5%) remained on treatment and 10 (43.5%) have discontinued treatment (the most common reason for discontinuation was disease progression [n=3; 13.0%]). the median duration of follow-up at the time of data cut-off was 9.7 months (range: 0.8–15.9). table 1. patient demographics, baseline characteristics, and exposure to cemiplimab locally advanced cscc (n=23) median age, years (range) 67 (47–96) ≥ 65 years, n (%) 13 (56.5) male, n (%) 17 (73.9) ecog performance status score, n (%) 0 13 (56.5) 1 10 (43.5) primary cscc site, n (%) head/neck 17 (73.9) extremity 5 (21.7) trunk 1 (4.3) prior systemic therapy for cscc, n (%) 6 (26.1) prior radiotherapy for cscc, n (%) 14 (60.9) median duration of cemiplimab exposure (range), weeks 43.3 (2.0–68.0) median number of cemiplimab doses administered (range) 22 (1–31) • neither median overall survival nor median progression-free survival had been reached at the time of data cut-off. the estimated probability of survival at 12 months was 91.1% (95% ci: 68.8–97.7). the estimated progression-free probability at 12 months was 65.6% (95% ci: 37.6–83.4). treatment-emergent adverse events • teaes regardless of attribution are summarized in table 3. • investigator-assessed treatment-related teaes are summarized in table 4. figure 1. study design ecog, eastern cooperative oncology group; iv, intravenously; pd-l1, programmed death-ligand 1; q2w, every 2 weeks; q3w, every 3 weeks. group 1 – adult patients with metastatic (nodal and/or distant) cscc group 2 – locally advanced cscc (without nodal or distant metastasis) group 3 – adult patients with metastatic (nodal and/or distant) cscc cemiplimab 3 mg/kg q2w iv, for up to 96 weeks (retreatment optional for patients with disease progression during follow-up) cemiplimab 350 mg q3w iv, for up to 54 weeks tumor imaging every 8 weeks for the assessment of efficacy (confirmatory scans performed no sooner than 4 weeks following initial documentation of tumor response) tumor imaging every 9 weeks for the assessment of efficacy tumor response assessment by an independent central review committee key inclusion criteria ● ecog performance status of 0 or 1 ● adequate organ function ● group 2: – at least one lesion measurable by digital medical photography – cscc lesion that is not amenable to surgery or radiation therapy per investigators’ assessment key exclusion criteria ● ongoing or recent (within 5 years) autoimmune disease requiring systemic immunosuppression ● prior treatments with anti-pd-1 or anti-pd-l1 therapy ● history of solid organ transplant, concurrent malignancies (unless indolent or not considered life threatening; for example, basal cell carcinoma), or hematologic malignancies. figure 2. clinical activity of tumor response to cemiplimab in patients who underwent photo evaluation per who criteria by independent central review plot shows the best percentage change in the sum of target lesion diameters from baseline for 20 patients who underwent photo evaluation per independent central review after treatment initiation. lesion measurements after progression were excluded. blue and red dotted lines indicate who criteria for partial response (≥50% decrease in the sum of target lesion diameters) and progressive disease (≥25% increase in the target lesion diameters). three patients that do not appear in the figure (but are included in the overall response analysis [table 2], per intention-to-treat) are: two patients with no evaluable post-treatment tumor assessment and one patient who did not have a measurable skin disease. be st p er ce nt ag e ch an ge in ta rg et le si on fr om b as el in e partial response progressive disease stable disease 100 80 60 40 20 0 –20 –40 –60 –80 –100 figure 3. change in target lesion per who criteria over time plot shows the percentage change in target lesion diameters from baseline over time. patients shown in this figure are the same as those in figure 2. horizontal dotted lines indicate criteria for partial response (≥50% decrease in the sum of target lesion diameters) and progressive disease (≥25% increase in the target lesion diameters). one patient (dashed blue line) had increased target lesion measurements at week 8 and week 16 that met criteria for progressive disease (by independent central review), followed by complete resolution of target lesions. this suggests that patients with locally advanced cscc may occasionally experience an increase in target lesions, followed by subsequent durable response. months 100 80 60 40 20 0 –20 –40 –60 –80 –100 pe rc en ta ge c ha ng e in ta rg et le si on fr om b as el in e 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 figure 4. time to response and duration of response in responding patients plot shows time to response and duration of response in the 10 responding patients. each horizontal line represents one patient. nine of the 10 patients remain in response and on study at time of data cut-off. one patient was censored (top line) after missing treatments due to co-morbidities and withdrawing consent from study; therefore, they no longer met the dual criteria of ongoing response per independent central review and ongoing study treatment. months pa tie nt s w ith re sp on se 0 2 4 6 8 10 12 14 16 18 20 stable disease unable to evaluate ongoing treatment ongoing study partial response complete response clinical efficacy • tumor response assessment, characteristics of tumor response, and examples of reductions in visible lesions following cemiplimab treatment are shown in table 2 and figures 2–4. • median duration of response has not been reached. the longest duration of response at the time of data cut-off is 12.9+ months. interim analysis of phase 2 results for cemiplimab, a human monoclonal antibody to programmed death-1, in patients with locally advanced cutaneous squamous cell carcinoma michael r. migden,1 carola berking,2 anne lynn s. chang,3 thomas k. eigentler,4 axel hauschild,5 leonel hernandez-aya,6 nikhil i. khushalani,7 karl d. lewis,8 friedegund meier,9 badri modi,10 danny rischin,11 dirk schadendorf,12 chrysalyne d. schmults,13 claas ulrich,14 jocelyn booth,15 siyu li,15 kosalai mohan,16 elizabeth stankevich,15 israel lowy,16 matthew g. fury16 1departments of dermatology and head and neck surgery, university of texas md anderson cancer center, houston, tx, usa; 2department of dermatology and allergy, munich university hospital (lmu), munich, germany; 3department of dermatology, stanford university school of medicine, redwood city, ca, usa; 4department of dermatology, university medical center tübingen, tübingen, germany; 5schleswig-holstein university hospital, kiel, germany; 6division of medical oncology, department of medicine, washington university school of medicine, st louis, mo, usa; 7department of cutaneous oncology, moffitt cancer center, tampa, fl, usa; 8university of colorado denver, school of medicine, aurora, co, usa; 9department of dermatology, university hospital dresden, dresden, germany; 10division of dermatology, city of hope, duarte, ca, usa; 11department of medical oncology, peter maccallum cancer centre, melbourne, australia; 12university hospital essen, essen and german cancer consortium, essen, germany; 13department of dermatology, brigham and women’s hospital, harvard medical school, boston, ma, usa; 14department of dermatology, venereology and allergology, skin cancer center charité, berlin, germany; 15regeneron pharmaceuticals, inc., basking ridge, nj, usa; 16regeneron pharmaceuticals, inc., tarrytown, ny, usa. poster presented at the 2018 fall clinical dermatology conference, october 18–21, las vegas, nevada (encore of eadv 2018 eposter presentation). microsoft word 8. 603 proof done.docx skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 62 brief articles lichen planopilaris associated with spray-on sunscreen timothy j. orlowski, md,1 h. harris reynolds, md,2 boni e. elewski, md2 1479th flying training group, aviation medicine department, naval hospital pensacola, pensacola, fl usa 2university of alabama at birmingham, department of dermatology, birmingham, al usa a 49 year old female was referred to our university-based dermatology outpatient clinic for a three year history of scarring hair loss affecting her anterior hairline and extending centrally in her part area (figure 1). exam was remarkable for patchy alopecia along the anterior hairline with posterior extension through the part line. decreased follicular density, perifollicular erythema, and perifollicular scale were noted on trichoscopy. the patient’s eyelashes and eyebrows were not affected. a punch biopsy was performed at the active edge of erythema. histopathology revealed scarring cicatricial alopecia consistent with lichen planopilaris. a complete blood count, comprehensive metabolic panel, and antinuclear antibody titer were unremarkable. she was started on hydroxychloroquine 400mg daily, minoxidil 5% foam daily, finasteride 2.5mg daily, and topical clobetasol 0.05% ointment daily. at her follow-up visit, our patient brought photos of a spray-on sunscreen she had been applying for one to two years prior to the onset of her hair loss. this sunscreen was applied directly to the areas of hair loss visible on physical exam. she had been applying the sunscreen to her central scalp, as this area was often exposed to sunlight due to the way her hair was parted. notably, this product contained homosalate and octisalate, two salicylates that act as chemical uv absorbers (table 1). we recommended she discontinue this product. follow-up was pending at the time of publication. figure 1. scarring alopecia extending posteriorly along the part area, corresponding with areas of sunscreen application. case report lichen planopilaris (lpp) and frontal fibrosing alopecia (ffa) have been linked to many cosmetic products that contain ultraviolet (uv) filters and new evidence points to an association with uv filters in hair-care products.1-3 we present a case report with clinical findings of a lpp/ffa overlap associated with spray-on sunscreen use. underlying the basis of this association are the similar trichoscopic and histologic findings of lpp and ffa, as well as, the possible association with regular use of facial sunscreen. abstract skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 63 table 1. active ingredients in implicated spray-on sunscreen. our patient’s regular, direct application of this sunscreen only to areas with visible disease preceded the onset of her scalp symptoms by one to two years. furthermore, some of this sunscreen’s active ingredients, namely homosalate and octisalate, are in the same family of chemical uv absorbers as the active ingredients reported by canavan et al. their case report parallels our patient presentation—caucasian females who developed lpp in the setting of spray-on scalp sunscreen use.1 both patients had a long history of sunscreen application to their frontal scalp and hair part as well as similar histologic findings on scalp biopsy.1 to our knowledge, this is one of only several case reports of lpp associated with scalp sunscreen use that has been reported in the literature.1-4 although further studies are needed to establish causality, these similar patient presentations could indicate potential correlation between regular sunscreen use and lichen planopilaris. large scale epidemiologic studies may be useful in shedding further light on the potential association between the use of chemical sunscreens and the development of lpp/ffa. conflict of interest disclosures: dr. orlowski was active duty air force at the time of submission. the views expressed are those of the authors and are not to be construed as official or as representing those of the us air force or the department of defense. dr. orlowski was a full time federal employee at the time portions of this work were completed. they are in the public domain. dr. elewski and dr. reynolds have no conflicts of interest to declare. funding: none corresponding author: timothy jay orlowski 101 e romana street apt 355 pensacola, fl 32502, usa tel: 847-370-7347 email: torlowski13@gmail.com references: 1. canavan, t., mcclees, s., duncan, j., & elewski, b. (2019). lichen planopilaris in the setting of hair sunscreen spray. skin appendage disord, 5(2), 108-110. 2. weston, g., & payette, m. (2015). update on lichen planus and its clinical variants. int j womens dermatol, 1(3), 140-149. 3. callander, j., frost, j., & stone, n. (2018) ultraviolet filters in hair-care products: a possible link with frontal fibrosing alopecia and lichen planopilaris. clin exp dermatol, 43(1), 69-70. 4. aldoori n, dobson k, holden cr, mcdonagh aj, harries m, messenger ag. (2016) frontal fibrosing alopecia: possible association with leaveon facial skin care products and sunscreens; a questionnaire study. br j dermatol, 175(4), 762767. discussion skin july 2021 1210 proof skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 414 brief article heroin-induced ulcer mimicking pyoderma gangrenosum deep patel, bs1, jennifer mardini, bs1, christopher chu, md2, max disse, md2, alexandra flamm, md2 1 penn state college of medicine, hershey, pa 2 department of dermatology, penn state hershey medical center, hershey, pa “skin popping” is a term used to describe repetitive subcutaneous injections with illicit substances such as heroin and cocaine1. “skin popping” is often due to extravasation of chemicals in the drug and can cause the formation of secondary tissue lesions, including thrombophlebitis, ulcerations, gangrene, and necrosis at and around the injection sites and can quickly evolve to limb amputation and death2,3. initial dermatological manifestations of “skin popping” may present similar to more common etiologies such as pyoderma gangrenosum (pg); however, all injectioninduced dermatological manifestations should be recognized and treated urgently to preserve function. information and reports in the dermatologic literature are sparse, but is becoming increasing relevant. we present a patient with lower extremity ulceration due to subcutaneous injection of heroin which resembled pg. a 29-year-old female with a history of intravenous and subcutaneous drug abuse presented for evaluation of a large skin ulcer on the left lower extremity. the skin manifestations began nine months prior when the patient injected heroin into her bilateral lower extremities. she subsequently developed an enlarging inflammatory nodule and ulcers at injection points of both her right thigh and left lower extremity, which were treated with irrigation and debridement. the patient reports that her right thigh wound healed well; however, the wound on her left lower extremity persisted and seems to have worsened after her debridement and multiple subsequent antibiotic courses. several cultures were previously obtained, which revealed 1+ pseudomonas aeruginosa, sensitive to ciprofloxacin. although the cultures showed p. aeruginosa colonization, pointing to ecthyma gangrenosum, the etiology of the ulcer was abstract subcutaneous injections of illicit substances may be performed by some patients citing several advantages by the user, and can present to clinic with ulcers that clinically mimic pyoderma gangrenosum. however, it is vital to recognize heroin-induced ulcers and treat urgently to preserve function. treatment requires a multidisciplinary approach with general medicine, dermatology, plastic surgery, wound care, infectious disease and addiction medicine. we present a patient with lower extremity ulceration due to subcutaneous injection of heroin which resembled pg. introduction case report skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 415 considered not due to chronic infection as four courses of ciprofloxacin treatment did not improve the skin lesion. the nonhealing wound has been treated with a variety of wound care modalities such as absorbent dressings with compression wraps with no improvement. the multi-disciplinary efforts for this patient included dermatology, infectious disease for microbial etiologies, rheumatology for systemic disease workup and vascular surgery for wound care. on physical exam, a 10x15cm welldemarcated deep ulcer with a beefy red, fibrinous base containing visible subcutaneous and granulation tissue and a rim of erythema and areas of undermined edges on the left lower extremity was observed (figure 1). the arms and legs had numerous well-healed hyperpigmented macules and patches, where patient notes past injection sites. of note, patient was afebrile and had a normal white blood cell count. figure 1. differential diagnosis included vasculitis, hepatitis b, superficial ulcerating rheumatoid necrobiosis however lab evaluation for systemic disease was negative. given the history of the worsening skin lesion after debridement and the characteristic appearance, the wound was biopsied by dermatology to assess for pyoderma gangrenosum (pg). punch biopsy at the edge of the ulcer revealed perivascular lymphoplasmacytic infiltrate without characteristic dense neutrophilic infiltrate of pg, and histopathology did not coordinate with pg (figure 2). tissue culture was also obtained for anaerobe, fungus, bacteria, and acid-fast bacilli, which were negative except one isolated colony of p. aeruginosa. figure 2. a, b patient was offered addiction medicine consultation, which she declined. she agreed to follow up and treatment with wound center with local wound care and debridement. follow up at the wound clinic one month after treatment revealed an improvement in ulcer size and appearance (figure 3). patient is a b skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 416 currently on suboxone and reported that she is no longer injecting heroin. she had no signs of subcutaneous injections. figure 3. our patient was diagnosed with a heroin induced ulcer secondary to subcutaneous injection. because of extravasation of chemicals in the drugs, subcutaneous injection of heroin and other illicit substances can result in ulcerations, gangrene, and necrosis to local tissue causing it to clinically resemble pg2,3. for example, krokodil, a synthetic addictive substitute for heroin, appears to be associated with necrotic and gangrenous tissue destruction more than other substances [4]. the presence of gasoline and hcl in krokodil induces discolored scale-like skin and ulceration, while venous extravasation of heroin leads to extensive necrosis of the skin and subcutaneous layer 4. the evolving nature of these exogenous-induced ulcers, however, may lead to limb amputation and death5. therefore, the importance of a broad differential diagnosis and confirmatory biopsy of the lesion is critical for cases resembling pg, especially in high risk patient populations. notably, other processes have been reported to mimic pg as well including bromoderma, cutaneous diphtheria, cutaneous cryptococcus, granulomatosis with polyangiitis, and metastatic crohn disease5-9. this further highlights the importance for a broad initial differential diagnosis in cases clinically resembling pg. in the present case, dermatology was consulted to assess for pg as the clinical findings were consistent with this condition. the dermatopathology of heroin ulcers have been found to show nonspecific findings such as leukocytoclastic vasculitis, dermal pigment deposition, non-specific ulceration/scarring and necrobiosis lipoidicalike dermatitis10. our case revealed perivascular lymphoplasmacytic infiltrate. more importantly, the characteristic dense and required neutrophilic infiltrates of pg were absent. along with the patient’s history of subcutaneous injection of heroin, a diagnosis of heroin-induced ulcer was made. increasing use of heroin and other illicit substances in our patients make it important for dermatologists to be aware of the cutaneous manifestations caused by subcutaneous injections of illicit drugs. our patient volunteered her drug use, however, many will not and thus it is important to be suspicious in high risk patients presenting with early manifestations of injection induced ulcerations, which may resemble other diseases such as pyoderma gangrenosum. treatment of these wounds will require a multidisciplinary approach including dermatology, infectious disease, wound care, plastic surgery and internal medicine. because of poor compliance, being lost to discussion conclusion skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 417 follow up and the natural history of this disease, these patients are at a higher risk for complications. conflict of interest disclosures: none funding: none corresponding author: deep patel, bs 500 university ave hershey pa 17033 phone: 717-531-5898 fax: 717-531-4702 email: dpatel3@pennstatehealth.psu.edu references: 1. alvi a, ravichandran d. an unusual case of breast ulceration. breast. 2006;15(1):115–116. 2. onesti mg, fioramonti p, fino p, et al. skin ulcer caused by venous extravasation of heroin. int wound j. 2014;11(4):409–411. 3. alves ea, grund jp, afonso cm, et al. the harmful chemistry behind krokodil (desomorphine) synthesis and mechanisms of toxicity. forensic sci int. 2015;249:207–213. 4. haskin, a., kim, n., & aguh, c. (2016). a new drug with a nasty bite: a case of krokodilinduced skin necrosis in an intravenous drug user. jaad case reports, 2(2), 174–176. https://doi.org/10.1016/j.jdcr.2016.02.007 5. oda f, tohyama m, murakami a, et al. bromoderma mimicking pyoderma gangrenosum caused by commercial sedatives. j dermatol. 2016;43(5):564–566. 6. morgado-carrasco d, riquelme-mc loughlin c, fustá-novell x, et al. cutaneous diphtheria mimicking pyoderma gangrenosum. jama dermatol. 2018;154(2):227–228. 7. kindle sa, camilleri mj, gibson le, et al. granulomatosis with polyangiitis mimicking classic inflammatory bowel disease-associated pyoderma gangrenosum. int j dermatol. 2017;56(1):e1–e3. 8. kikuchi n, hiraiwa t, ishikawa m, et al. cutaneous cryptococcosis mimicking pyoderma gangrenosum: a report of four cases. acta derm venereol. 2016;96(1):116–117. 9. avilés-izquierdo ja, suárez-fernández r, lázaro-ochaita p, et al. metastatic crohn's disease mimicking genital pyoderma gangrenosum in an hiv patient. acta derm venereol. 2005;85(1):60–62. 10. tse jy, adisa m, goldberg lj, et al. dermatopathologic manifestations of intravenous drug use. j cutan pathol. 2015;42(11):815–823. skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 278 covid concept new bullous eruptions in a covid-19 positive patient in an intensive care unit angela kim, do, mph1, muneeb khan, md2, ann lin, do, ms1, hongbei wang, md, phd3, louis siegel, do1, suzanne sirota-rozenberg, do1 1division of dermatology, st. john’s episcopal hospital, far rockaway, ny 2department of family medicine, st. john’s episcopal hospital, far rockaway, ny 3department of dermatopathology, hofstra northwell school of medicine, hempstead, ny bullous pemphigoid (bp) is an autoimmune blistering disorder that most commonly affects older adults and is characterized by tense bullae. although most cases of bp have no precipitating factors, virus-induced bps have been reported.1 we describe a case of new onset bp in a patient with acute covid-19 infection during the pandemic peak in new york. a 76-year-old male from a nursing home with a past medical history of hypertension, diabetes mellitus, hyperlipidemia, and major depressive disorder presented to the emergency department with altered mental status, hypotension, tachycardia, hypoxia, and a fever of 100.9f. a positive covid-19 polymerase chain reaction, labs with elevated d-dimer, lactate dehydrogenase, ferritin, c-reactive protein, and erythrocyte sedimentation rate, and a chest x-ray showing bilateral infiltrates, were all consistent with progressing covid-19 respiratory syndrome. following respiratory failure, the patient was intubated and admitted to the intensive care unit. patient’s home medications were discontinued at admission. hydroxychloroquine and azithromycin were initiated per hospital protocol, along with intravenous methylprednisolone and anakinra. there were no skin findings initially. on day 3, multiple 2mm to 6cm tense bullae developed on his left arm(figure 1). a shave biopsy of a 2mm intact bullae for hematoxylin & eosin(h&e) and a 3mm perilesional punch biopsy for direct immunofluorescence(dif) were performed. the h&e stain(figure 2) showed a cell-poor subepidermal bulla, while dif(figure 3) revealed linear abstract bullous pemphigoid (bp) is an autoimmune blistering disorder that typically occurs in older adults. the etiopathogenesis of bp is unclear, although viral triggers have been reported.1 we present a case of new onset pauci-cellular bp in a patient admitted to intensive care unit from an acute covid-19 infection. new onset bullous eruptions in the setting of covid-19 infection should elicit suspicions and consider the differential diagnosis of bp. introduction case presentation skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 279 figure 1. bullous pemphigoid. clinical presentation of tense and flaccid bullae with erosions on left upper extremity figure 2. bullous pemphigoid. hematoxylin & eosin histologic examination of biopsy specimen showing a pauci-cellular subepidermal bullae with minimal infiltrate immunoglobulin g(igg) at the dermoepidermal junction. bullae were ruptured with a sterile needle, and wound care was rendered with twice-daily applications of topical betamethasone dipropionate, augmented 0.05% ointment. no new blisters recurred. patient recovered overall and was extubated and discharged. figure 3. bullous pemphigoid. direct immunofluorescence image of perilesional punch biopsy specimen showing linear igg the etiopathogenesis of bp is complex and not yet fully understood, although viral infections with hiv, ebv, cmv, hhv, hhv6, hbv, and hcv have been reported to trigger bp.1 a report of three pediatric cases describes post-immunization and post-viral induced bp.2 to date, there is little information on the association between severe acute respiratory syndrome coronavirus 2 (sars-cov-2) virus and bp and more studies are needed. discussion skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 280 without a history of bp, our intubated patient was non-verbal at the time of examination and therefore was unable to report any prodromal skin pruritus or tenderness. new onset bullous eruptions occurred while in critical care for covid-19 and despite being on a systemic steroid. cutaneous symptoms of sars-cov-2 are reported to present as petechial-, erythematous-, urticarial-, and pernio-like rashes,3 which our patient did not have. although the patient fit the usual age group for new bp onset, the mechanism of induction, especially in the setting of sarscov-2, remains unclear. on day 1-2 of admission, the patient received 2l of fluids/day and was oliguric, but urine output normalized on day 3 when skin eruptions occurred. of note, the right upper extremity and lower extremities were not edematous and unaffected throughout admission. given these facts and the paucicellar subepidermal bullae, a differential diagnosis of edema blisters must be considered. edema blisters are generally observed on lower extremities and are associated with chronic venous insufficiency, congestive heart failure, hepatic or renal failures, which were negative in our patient.4 although paucicellular, our h&e did not show any epidermal spongiosis or dermal edema, which is evident in edema blisters. typically, eosinophils are the defining inflammatory infiltrates in bp. although pauci-cellular bp is uncommon, studies have demonstrated igg depleting bp180 in the hemidesmosomes and weakening the lamina lucida without complement activation in bp.5,6 this may explain the minimal inflammation within the bulla and positive igg on dif in our case. other reasons may include systemic steroid received since admission or biopsy specimen size not ample enough to visualize eosinophils. most bp dif shows igg and/or c3 in the basement membrane zone. the sensitivity of dif in bp ranges 88.3-84%7,8; additionally, in a large group of bp patients, dif detected igg was 91.4% and 73.6% for c3. isolated igg deposition was 19.8%.8 our patient showed a unique case of bp with positive igg but negative for c3, iga, and igm on dif. false positive dif can occur if biopsies are taken from lower extremities or from the bullae itself, but our dif was taken from the upper extremity, the only location involved, and from an uninvolved perilesional skin within 1cm from a blister. correlating dif with elisa testing for anti-bp180 and anti-bp230 antibodies and/or indirect immunofluorescence(iif) may have been helpful. however, people without bp can also have positive autoantibodies on elisa. elisa and iif were not performed on our patient when dermatopathology resulted, which was about a week after the biopsy, as lesions resolved and it did not change our management. a cell-poor subepidermal blister and linear igg on dif may be seen in epidermolysis bullosa acquisita(eba). however, eba typically occurs in a younger age group, on sites of trauma, and heals with scarring, dyspigmentation, and milia formation. bullous eruptions on our patient occurred on day 3 without any previous or current iv access on the affected extremity. furthermore, there was no trauma reported or observed on the physical exam. upon topical treatment, all lesions on our patient resolved and healed without scarring. although our patient had a history of diabetes, positive dif ruled out bullous diabeticorum, edema blister, and coma blister, which may have negative dif or positive igm and c3.4 skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 281 drug-induced bp, which is triggered by a combination of genetic predisposition and inciting medications, can be considered. the exact mechanism is not well elucidated, but it leads to alteration of the immune response to the epidermal basement membrane.9 our patient’s long-term home medications were discontinued at admission until discharge and were non-contributory. a drug chart while inpatient was created, and no inciting medications commonly associated with bp were given. initially, a dose of vancomycin and piperacillin/tazobactam each was given. vancomycin can induce linear iga bullous dermatosis but dif would show linear iga deposition, which was negative in our patient. no report has shown association between bp and hydroxychloroquine or azithromycin. bullous eruption only occurred on our patient’s left upper extremity. other unilateral covid related rashes have been reported,10,11 and reasons behind its localized presentations are still unclear. a report of a unilateral bp on one leg with chronic venous stasis, speculates that inflammation from stasis may have triggered the bp.12 inflammation, as evidenced by serum markers, may have contributed to our bullous eruption. immunosuppressives and anti-inflammatory medications are mainstay therapies for bp. in our case, potent topical corticosteroid resolved our localized bp when the systemic corticosteroid for the respiratory disease did not help. more studies are needed to understand the complexities of sars-cov-2 and bp separately and together. when encountering new bullous eruptions in patients with active sars-cov-2, clinicians should take caution and consider bp in their differential diagnosis as timely diagnosis and management can improve patient outcome. acknowledgement: we would like to thank dr. sadaf sheikh (department of pathology, st. john’s episcopal hospital, far rockaway, ny) for providing the h&e pathology photos for our case conflict of interest disclosures: none funding: none corresponding author: angela kim, do, mph division of dermatology st. john’s episcopal hospital 327 beach 19th street far rockaway, new york, 11691 phone: 718-869-7108 fax: 408-827-9056 email: angelakim86@gmail.com references: 1. jang h, jin yj, yoon ch, et al. bullous pemphigoid associated with chronic hepatitis c virus infection in a hepatitis b virus endemic area: a case report. medicine (baltimore). 2018;97(15):e0377. doi:10.1097/md.0000000000010377 2. baroero l, coppo p, bertolino l, et al. three case reports of post immunization and post viral bullous pemphigoid: looking for the right trigger. bmc pediatr. 2017;17(1):60. published 2017 feb 23. doi:10.1186/s12887-017-0813-0 3. ortega-quijano d, jimenez-cauhe j, seldaenriquez g, et al. algorithm for the classification of covid-19 rashes, journal of the american academy of dermatology (2020), doi: https://doi.org/10.1016/j.jaad.2020.05.034. 4. sami n, yeh sw, ahmed ar. blistering diseases in the elderly: diagnosis and treatment. dermatol clin. 2004 jan;22(1):73-86. doi: 10.1016/s07338635(03)00116-5. pmid: 15018011. freeman ee, mcmahon de, lipoff jb, et al. 5. hiroyasu s, ozawa t, kobayashi h, et al. bullous pemphigoid igg induces bp180 internalization via a macropinocytic pathway. am j pathol. 2013;182(3):828-840. doi:10.1016/j.ajpath.2012.11.029 6. iwata h, kamio n, aoyama y, et al. igg from patients with bullous pemphigoid depletes cultured keratinocytes of the 180-kda bullous pemphigoid antigen (type xvii collagen) and weakens cell attachment. j invest dermatol. 2009;129(4):919-926. doi:10.1038/jid.2008.305 7. buch ac, kumar h, panicker n, misal s, sharma y, gore cr. a cross-sectional study of direct mailto:angelakim86@gmail.com skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 282 immunofluorescence in the diagnosis of immunobullous dermatoses. indian j dermatol. 2014 jul;59(4):364-8. doi: 10.4103/00195154.135488. pmid: 25071256; pmcid: pmc4103273. 8. meijer jm, diercks gfh, de lang ewg, pas hh, jonkman mf. assessment of diagnostic strategy for early recognition of bullous and nonbullous variants of pemphigoid. jama dermatol. 2019 feb 1;155(2):158-165. doi: 10.1001/jamadermatol.2018.4390. pmid: 30624575; pmcid: pmc6439538. 9. verheyden mj, bilgic a, murrell df. a systematic review of drug-induced pemphigoid. acta derm venereol. 2020 aug 17;100(15):adv00224. doi: 10.2340/00015555-3457. pmid: 32176310. 10. glick lr, fogel al, ramachandran s, barakat la. unilateral laterothoracic exanthem in association with coronavirus disease 2019. jaad case rep. 2020 sep;6(9):900-901. doi: 10.1016/j.jdcr.2020.07.020. epub 2020 jul 21. pmid: 32835047; pmcid: pmc7372280. 11. karaca z, yayli s, çalışkan o. a unilateral purpuric rash in a patient with covid-19 infection. dermatol ther. 2020 jul;33(4):e13798. doi: 10.1111/dth.13798. epub 2020 jul 8. pmid: 32530130; pmcid: pmc7300488. 12. shi, c. r., charrow, a., granter, s. r., christakis, a., & wei, e. x. (2018). unilateral, localized bullous pemphigoid in a patient with chronic venous stasis. jaad case reports, 4(2), 162–164. https://doi.org/10.1016/j.jdcr.2017.09.032 skin november 2017 volume 1 issue 3 copyright 2017 the national society for cutaneous medicine 165 brief articles ulcerative tinea corporis in an immunosuppressed patient lizy mariel paniagua gonzalez md a , alison lowe md b , michael wilkerson md b a university of texas medical branch department of internal medicine, galveston, tx b university of texas medical branch department of dermatology, galveston, tx immunosuppression increases the risk for the development of many opportunistic infections including legionella, nocardia, cytomegalovirus, aspergillus, coccidiomycosis and cryptococcus among several others. trichophyton rubrum is the most common cause of dermatophytosis including tinea corporis, tinea pedis, and tinea unguium, regardless of immune status. 1-3 immunosuppressed patients, however, are at an increased for dermatophyte infection, which can become invasive in this population. 1 lillis et al demonstrated dermatophytosis in 42% of renal transplant recipients, with duration of infection lasting from 15 days up to 10 years. 4 in immunocompetent patients, dermatophytes cause superficial infection of the nails, hair, and stratum corneum, resulting mostly commonly in a characteristic annular erythematous scaly plaque. 3 dermatophytosis in immunosuppressed patient may additionally present with more aggressive invasion into the dermis or subdermis, can even progress to life threatening disseminated disease. 2 we present a case of invasive tinea corporis abstract worldwide, trichophyton rubrum is the most common cause of dermatophytosis. infection is classically superficial, limited to the cornified layers of the skin, and may be accompanied by varying degrees of inflammation. dermatophyte invasion is limited by multiple host factors, including sebum production, an intact skin barrier, and immunocompetence. we describe a 65 year old gentleman with a history of diabetes mellitus, hypertension, nephrogenic systemic fibrosis, and immunosuppressed status due to renal transplant who presented with a non-healing ulcer of the left dorsal hand. further examination revealed palmar erythema and scale as well as annular erythematous plaques with peripheral scale on his bilateral knees. laboratory testing yielded the diagnosis of tinea corporis, with bacterial superinfection of the left dorsal hand. the patient was started on systemic antimicrobials with complete healing of the ulcer along with total clearance of the rash. this case highlights an unusual presentation of invasive trichophyton rubrum in the setting of immunosuppression and nephrogenic systemic fibrosis. introduction skin november 2017 volume 1 issue 3 copyright 2017 the national society for cutaneous medicine 166 due to trichophyton rubrum in a renal transplant patient. a 65 year old male with a complex past medical history of diabetes mellitus type ii, hypertension, nephrogenic systemic fibrosis, atrial fibrillation, peripheral vascular disease, coronary artery disease, and renal transplantation years prior on immunosuppressive therapy was admitted for evaluation of a non-healing ulcer on the left dorsal hand. the patient presented with several month history of a rash on his left dorsal hand. the rash started as “small bumps”, which he had been treating with clobetasol topically. he also kept the area covered with a glove. about two weeks prior to admission the rash became acutely worse and painful. he was started on doxycycline by an outside dermatologist without much change. he had also been treating a rash on his legs with topical corticosteroids. of note, three years prior to presentation the patient had undergone workup for suspected nephrogenic systemic fibrosis. biopsy at the time showed thickened dermal collagen and dermal edema. dermatology was consulted due to concern for pyoderma gangrenosum versus arterial ulcer in the setting of peripheral vascular disease. physical examination of the left dorsal hand revealed a well demarcated coalescing ulcers with yellow fibrin and granulation tissue to base as well as surrounding induration, erythema, and sloughing (figure 1). additionally, erythema and scale were on the palmar and hypothenar areas of both hands and the patient had annular pink plaques with scale on bilateral knees. the potassium hydroxide (koh) preparation performed from the knees showed septated hyphae. biopsy of the left dorsal hand showed an ulcer with adjacent spongiotic epidermis and epidermal crust with periodic acid schiff (pas) positive. culture of the left hand was negative for viral infection but grew enterococcus faecalis, and staphylococcus epidermis. the patient was diagnosed with tinea corporis with concomitant superinfection. he was started on systemic antibiotics as well as topical and systemic antifungals with marked improvement of symptoms. he was discharged on voriconazole 200 mg twice daily for 60 days and miconazole 2% ointment in addition to local wound care. upon one month follow up with dermatology the rash had resolved and the ulcers were nearly fully healed (figures 2-3). figure 1: well-demarcated coalescing ulcers with yellow fibrin and granulation tissue to base and surrounding induration/erythema/sloughing on the left dorsal hand case report skin november 2017 volume 1 issue 3 copyright 2017 the national society for cutaneous medicine 167 figure 2: marked improvement after one month of systemic antifungal treatment figure 3: clinical improvement following one month of treatment with systemic antifungal regimen transplant patients on immunosuppressive medications are at increased risk for the development of a variety of opportunistic infections as well as for atypical and severe presentations of more common diseases. patients taking immunosuppressive medications have a decreased cellular immunity which is crucial in fighting infections. 6 the risk of developing aggressive dermatophytosis is directly proportional to the chronicity of immunosuppression, and may also be influenced by the specific medications selected. specifically, prednisone causes delayed desquamation and thickening of the stratum corneum, a contributing to the increased incidence and duration of dermatophytosis in patients taking this medication alone or as part of their immunosuppressive regimen. 1 confounding environmental factors in this patient’s case included the use of a super-potent topical steroid, its effect enhanced by occlusion of the area with a glove. invasive dermatophyte infection has been reported to involve the dermal, and subcutaneous tissue, as well as the hair follicle as in majocchi’s granuloma. 2 deep invasion is commonly limited to the subcutaneous tissue and only very rarely disseminates systemically. 5,7 the clinical presentation of aggressive dermatophyte infection is variable. lesions typically involve the feet, lower legs, and/or buttocks. they may be firm or fluctuant, dusky colored, or hemorrhagic, and may be painful. 2 a case of trichophyton rubrum presenting as multiple hard cutaneous nodules on the lower extremities has been reported. 5 additional manifestations include draining sinuses, verrucous papules, and blastomycosis like lesion. 7 bacterial, viral, or parasitic superinfection is not uncommon, and previous reports have demonstrated nocardia 7 herpes simplex, sarcoptes scabiei, stenotrophomas maltophilia, staphylococcus aureus. 2 discussion skin november 2017 volume 1 issue 3 copyright 2017 the national society for cutaneous medicine 168 clinicians should have a strong suspicion for atypical presentations of common infections in transplant patients. wound and tissue cultures may be necessary for definitive diagnosis. sufficient treatment typically requires administration of systemic antifungal agents as well as broad spectrum antibiotics and/or antivirals. topical and systemic antifungal administrations have been used for resolution of the deep invasive dermatophyte infection. systemic medications include itraconazole or terbinafine 5 , and topical ketoconazole, miconazole and griseofulvin creams 8 requiring weeks to months of administration. in severe infections, amphotericin b was administered for resolution of the skin lesions. 2 due to iatrogenic immunosuppression for a renal transplant, compounded by certain environmental conditions, this patient developed invasive tinea corporis complicated by bacterial superinfection. he was started on systemic antifungals, topical antifungals, and systemic antibiotics with marked improvement of symptoms. upon one month follow up with dermatology the rash had resolved and the ulcers were nearly fully healed. conflict of interest disclosures: none. funding: none. corresponding author: lizy mariel paniagua department of internal medicine university of texas medical branch galveston, tx 77555 713-614-71769 lmpaniag@utmb.edu references: 1. budihardja, d., freund, v., mayser, p. widespread erosive tinea corporis by arthroderma benhamiae in a renal transplant recipient: case report. mycoses. 2010;53(6):530-532. 2. grossman, m.r., pappert, a.s, garzon, m., silvers, d.n. invasive trichophyton rubrim infection in the immunocompromised host: report of three cases. j am acad dermatol. 1995;33:315-8. 3. lillis, j.s., dawson, e.s., chang, r., white, c.r. disseminated dermal trichophyton rubrum infectionan expression of dermpatophyte dimorphism? j cutan pathol. 2010;37:11681169. 4. sclvi, g.s, kamalam, a., ajithados, k., janaki, c., thambiah, a.s. clinical and mycological features of dermatophytosis in renal transplant recipients. mycoses. 1999;42:75-78. 5. nir-paz, r., elinav, h. pierard, g.e., walker, d., maly, a., et.al. deep infection by trichophyton rubrum in an immunocompromised patient. j. of clin mircrobiol. 2003;41(11):5298-5301. 6. smith, k.j., welsh, m., skelton, h. trichophytum rubrum showing deep dermal invasion directly from epidermis in immunosuppressed patients. british j. of dermatol. 2001;145:344348. 7. seckin, d., arikan, s., haberal, m. deep dermatophytosis caused by tichophyton rubrum with concomitant disseminated nocardiosis in renal transplant recipient. j am. acad dermatol. 2004;51:5101-5104. 8. marconi, v.c., kradin, r., marty, f.m., hospenthal, d.r., kotton, c. disseminated dermatophytosis in a patient with hereditary hemochromatosis and hepatic cirrhosis: case report and review of the literature. med mycol. 2010; 48(3):518-527. skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 139 rising derm stars® the ram relaxation technique: a painless biopsy method. a needle-free, anesthesia-free shave biopsy approach jacquiline habashy, md1 1department of dermatology, larkin community hospital, south miami, fl background/objectives: a shave biopsy is the most commonly used method in dermatology because of its efficient procedure time, the ease of wound care, and cost. shave biopsies are used for raised lesions, in cases where the clinician is suspecting an epidermal process, or a palpable dermal neoplasm. due to lesions having a predominantly convex and exophytic nature, the rrt can be successfully completed with minimal or no pain. the limitations for this technique would include pigmented lesions suspicious of melanoma, which are often biopsied with elliptical excisions. such procedures require the use of local anesthesia due to increased depth of incision. in addition to the physical pains of a needle injection, patients often report tremendous anxiety, comparable to many invasive medical procedures. patients may experience anxiety in anticipation of or during procedures used for screening, such as skin biopsies. this particular phobia is a subset of acute procedure anxiety and is diagnosed only when the patient’s fears are targeted to the procedure and its immediate effects, such as pain and bleeding, rather than fears not particular to the procedure itself, for example the illness that is being screened or diagnosed. methods: the current study investigates alternative approaches to reduce patients’ anxiety levels, and suggests that physicianguided relaxation techniques, such as deep breathing, prior to the procedure may consciously produce the body’s natural relaxation response, resulting in a feeling of calmness and well-being. previous research has confirmed that pain perception is influenced by anxiety and stress levels prior to the cognitive stressor, such as a medical procedure. another alternative method to decrease the pain of injection is by pinching the skin area to be injected. this technique is derived from the gate control theory of pain, which declares that a non-painful sensory input effectively blocks the transmission of other painful sensations nearby. therefore, stimulation by non-painful input is able to suppress pain. we have been able to implement both methods and have seen great results due to a decrease in anxiety levels per patient, which further leads to decreased pain perception. while it is difficult to comparatively quantify the level of anxiety felt by patients who receive injections versus those who opt for the rrt, the overwhelming responses have been highly favorable for those who forego the injection techniques. table 1 includes all 20 patients in skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 140 the study with their location of biopsy and pain level. results: the current study is a unique approach to performing skin biopsies and illustrates the need for further investigation for its efficacy in a larger population. overall, patients undergoing biopsies without anesthetic injection had better outcomes than those patients that received injections. level of pain was significantly reduced, lower sense of anxiety was achieved, and accurate samples were attainable. conclusion: this ram relaxation technique method has proven to be a beneficial alternative for patients that are anxious about experiencing discomforting pain, have contraindications to the anesthesia or prefer an alternative to avoid medications and injections if possible. table 1 patient number location of biopsy pain level (010) 1 nose 0 2 nose 0 3 nose 0 4 ankle 0 5 cheek 0 6 neck 0 7 columella 0 8 left medial leg above the tibia 0 9 nose 0 10 left temple 0 11 chin 0 12 right forehead 2 13 cheek 2 14 nose 2 15 right temple 2 16 cheek 0 17 ear 0 18 nasolabial fold 6 19 nose 0 20 ear 1 references: 1. alguire pc, mathes bm. skin biopsy techniques for the internist. j gen intern med. 1998;13(1):46–54. 2. neitzel cd. biopsy techniques for skin disease and skin cancer. oral maxillofac surg clin north am. 2005;17(2):143– 146. 3. tran kt, wright na, cockerell cj. biopsy of the pigmented lesion—when and how. j am acad dermatol. 2008;59(5):852–871. 4. bienvenu oj, eaton ww. the epidemiology of blood-injection-injury phobia. psychol med 1998; 28:1129. 5. dusek ja, benson h. mind-body medicine: a model of the comparative clinical impact of the acute stress and relaxation responses. minnesota medicine. 2009;92(5):47–50. poster presented at the 37th fall clinical dermatology conference | las vegas, nv | october 18-21, 2018 clinical management of anticholinergic adverse events with glycopyrronium cloth, a treatment for primary axillary hyperhidrosis authors: d. pariser,1 r. gopalan,2 j. drew,2 l. green3 1eastern virginia medical school and virginia clinical research, inc., norfolk, va; 2dermira, inc., menlo park, ca; 3george washington university school of medicine, washington, dc introduction • hyperhidrosis affects an estimated 4.8% of the us population, or approximately 15.3 million people, and negative psychological consequences (eg, anxiety, depression) are associated with the disorder1 • the impact of hyperhidrosis on quality of life is comparable to, or greater than, the impact of psoriasis or eczema2 • glycopyrronium tosylate (gt) is a topical anticholinergic approved in the us for primary axillary hyperhidrosis in patients 9 years and older (glycopyrronium cloth, 2.4%, for topical use) • gt safety and efficacy were evaluated in two, replicate, randomized, phase 3 clinical trials (atmos-1 and atmos-2); the primary efficacy and safety results of these studies have been previously reported, and in these trials, gt reduced sweating severity and sweat production compared to vehicle and was generally well tolerated3 objective • to examine the safety and tolerability profile of gt in the atmos-1 and atmos-2 trials and how treatment-emergent adverse events (teaes) associated with anticholinergic compounds were managed/resolved during those trials methods atmos-1 and atmos-2 study design and patients • atmos-1 (nct02530281; sites in the us and germany) and atmos-2 (nct02530294; us sites only) were replicate, randomized, parallel-group, 4-week, double-blind, phase 3 clinical trials3 (figure 1) • patients with primary axillary hyperhidrosis were randomized (2:1) to gt 3.75% topical solution (equivalent to 2.4% glycopyrronium) or vehicle applied once daily to each axilla • eligible patients were ≥9 years of age (patients <16 years were only recruited at us sites), had primary axillary hyperhidrosis for ≥6 months, gravimetrically-measured sweat production of ≥50 mg/5 min in each axilla, axillary sweating daily diary (asdd) sweating severity (item 2)4 score ≥4, and hyperhidrosis disease severity scale (hdss) grade ≥3 • patients were excluded for history of a condition that could cause secondary hyperhidrosis; prior surgical procedure or treatment with a medical device for axillary hyperhidrosis; treatment with iontophoresis within 4 weeks or treatment with botulinum toxin within 1 year for axillary hyperhidrosis; axillary use of nonprescription antiperspirants within 1 week or prescription antiperspirants within 2 weeks; new or modified psychotherapeutic medication regimen within 2 weeks; and/or treatment with medications having systemic anticholinergic activity, centrally acting alpha-2 adrenergic agonists, or beta-blockers within 4 weeks unless dose had been stable ≥4 months and was not expected to change figure 1. study design week 0 week 4 atmos-1 and atmos-2 2:1 randomization atmos-1/atmos-2 n=344/353 gt (n=229/234) vehicle (n=115/119) gt, topical glycopyrronium tosylate assessments • coprimary endpoints assessed at week 4 were asdd item 2 responder rate (≥4-point improvement from baseline) and mean absolute change from baseline in gravimetricallymeasured sweat production (average of both axillae) • teaes, including relationship to study drug, were recorded throughout the trial – patients were asked about adverse events in a non-specific manner using open-ended questions; specific inquiry and evaluation regarding reported adverse events were to be conducted when applicable • blurred vision, mydriasis, and symptoms associated with urinary retention/hesitation were identified as teaes of special interest based on their known association with anticholinergic compounds • dose interruptions were allowed for intolerable treatment-related adverse events and mandated for treatment-related blurred vision and symptoms associated with urinary hesitancy, obstruction or retention (study drug was to be subsequently resumed based on clinical judgment) • patients with symptoms suggestive of urinary retention were to be evaluated for its clinical course; for symptoms of obstruction, patients were to be referred to a urologist or for emergency care • patients who complained of blurred vision were to be carefully evaluated to determine if the patient inadvertently touched the eye(s) after application of study drug – if there was no history of inadvertent introduction of study drug into the eye, the patient was to be evaluated to rule out any serious acute condition – if the blurred vision continued for >24 h, the patient was to be evaluated by an ophthalmologist or referred to emergency care results • in the pooled population of atmos-1 and atmos-2, 463 patients were randomized to gt and 234 to vehicle; 426 (92.0%) and 225 (96.2%) completed the trials, respectively • individual trial and pooled data for gt versus vehicle showed significantly higher asdd item 2 response rates (≥4-point improvement in sweating severity) and reduced sweat production at week 4 compared to baseline (coprimary endpoints)3 treatment-emergent adverse events • the frequency of teaes in the pooled population (56.0% gt, 32.3% vehicle) was similar to the individual trials (atmos-1: 54.2% gt, 28.9% vehicle; atmos-2: 57.8% gt, 35.6% vehicle) • consistent with individual studies, teaes in the pooled population were mostly mild or moderate in severity, transient, and infrequently led to discontinuation (table 1) • commonly reported teaes (≥5% of patients) in the gt group included some events associated with anticholinergic activity (dry mouth [24.2% gt, 5.6% vehicle] and mydriasis [6.8% gt, 0% vehicle]); other common teaes were application site pain (8.7% gt, 9.5% vehicle), oropharyngeal pain (5.7% gt, 1.3% vehicle) and headache (5.0% gt, 2.2% vehicle) (table 1) teaes leading to drug interruption or dose reduction (eg, every-other-day dosing) • a total of 6.3% of patients in the gt group and 2.2% of patients in the vehicle group experienced teaes that led to drug interruptions during the trials (table 1) – in the gt group, the most common teaes that led to drug interruptions were dry mouth and mydriasis (9 patients [1.9%] each), urinary hesitation (6 patients [1.3%]), vision blurred (5 patients [1.1%]), and headache, oropharyngeal pain, and constipation (2 patients [0.4%] each) – in the vehicle group, teaes that led to drug interruptions most commonly included application site pain and application site irritation (2 patients [0.9%] each) • a total of 5.2% of patients in the gt group and 0 patients in the vehicle group experienced teaes that led to dose reduction (eg, every-other-day dosing) during the trials (table 1) – in the gt group, the most common teaes that led to dose reduction were dry mouth (15 patients [3.3%]), dry eye (3 patients [0.7%]), pruritus and urinary hesitation (2 patients [0.4%] each) • all teaes leading to drug interruptions or dose reductions were mild or moderate table 1. safety overview and teaes through week 4 in atmos-1 and atmos-2 (pooled safety population) n (%) vehicle (n=232) gt (n=459) teaes any 75 (32.3) 257 (56.0) drug-related 38 (16.4) 179 (39.0) seriousa 0 2 (0.4)b led to drug interruption 5 (2.2) 29 (6.3) led to dose reduction (eg, every-other-day dosing) 0 24 (5.2) discontinuations due to teae 1 (0.4) 17 (3.7) deaths 0 0 teaes by intensity mild 53 (22.8) 170 (37.0) moderate 22 (9.5) 83 (18.1) severe 0 4 (0.9) common teaes reported in ≥5% of patients in either treatment arm in pooled population dry mouthc 13 (5.6) 111 (24.2) application site pain 22 (9.5) 40 (8.7) mydriasisc 0 31 (6.8) oropharyngeal pain 3 (1.3) 26 (5.7) headache 5 (2.2) 23 (5.0) anticholinergic teaes reported in >2% of patients in either treatment arm in atmos-1 or atmos-2 dry mouthc 13 (5.6) 111 (24.2) mydriasisc 0 31 (6.8) urinary hesitation 0 16 (3.5) dry eye 1 (0.4) 11 (2.4) blurred vision 0 16 (3.5) nasal dryness 1 (0.4) 12 (2.6) constipation 0 9 (2.0) urinary retention 0 7 (1.5) a serious teaes: atmos-1: moderate unilateral mydriasis, considered related to study drug; atmos-2: moderate dehydration, considered not related to study drug b serious teaes are those that: resulted in death, were immediately life threatening, required inpatient hospitalization, resulted in persistent or significant disability, or judged to require medical/surgical attention in order to avoid any of the previously mentioned outcomes c mydriasis and dry mouth appear twice in the table since they meet criteria for common teaes and are associated with anticholinergic use gt, topical glycopyrronium tosylate; teae, treatment-emergent adverse event teaes of special interest • teaes of special interest (blurred vision, mydriasis, and symptoms associated with urinary retention/hesitation) occurred in 13.3% (61/459) of gt-treated patients and no vehicle-treated patients (table 2) – most were considered related to study drug, of mild to moderate severity, and transient – severe teaes of special interest occurred in only one subject who had both severe mydriasis and severe urinary retention; these events, along with mild blurred vision and teaes of dry mouth (severe) and anhidrosis (severe), led to discontinuation, and all resolved after study drug withdrawal – one subject had a serious teae of unilateral mydriasis of moderate severity; given a head injury the prior week, the subject was hospitalized to rule out a central nervous system disorder, and the event resolved after study drug withdrawal • among the 6.8% of pooled gt-treated patients experiencing mydriasis, most events were unilateral (74.2% [23/31]), while most blurred vision events were bilateral (68.8% [11/16]); treatment was not discontinued in most cases (table 2) • in general, teaes of special interest resolved within 3-14 days, despite continued application of study drug or, did not recur upon treatment resumption – the duration of adverse events could be self-reported by patients but also could be noted as part of a symptom directed physical exam – a total of 80 events of teaes of special interest occurred in 61 patients; nine of these events (9/80 [11.3%]) lasted for >14 days and included 3 events of vision blurred, 2 events of urinary hesitation, and single events of mydriasis, nocturia, pollakiuria, and urinary retention table 2. teaes of special interest n (%) vehicle (n=232) gt (n=459) mydriasis 0 31 (6.8) led to discontinuation -4 (0.9) blurred vision 0 16 (3.5) led to discontinuation -2 (0.4) urinary hesitancy/retention 0 26 (5.7) urinary hesitation led to discontinuation 0 -16 (3.5) 3 (0.7) urinary retention led to discontinuation 0 -7 (1.5) 4 (0.9) urine flow decreased led to discontinuation 0 -3 (0.7) 1 (0.2) dysuriaa 0 1 (0.2) nocturia 0 1 (0.2) pollakiuria 0 1 (0.2) a this patient had symptoms of urinary hesitation, but the event was coded as dysuria and not reported as a teae of special interest gt, topical glycopyrronium tosylate; teae, treatment-emergent adverse event • most teaes of special interest resolved without any drug interruption or withdrawal (figure 2) – for patients with mydriasis or blurred vision, over half had the event resolve without study drug interruption or discontinuation – eight patients had both mydriasis and blurred vision (all concurrent), and for 6 of 8 patients, the events resolved during drug interruption or following discontinuation • in general, teaes of special interest did not recur upon treatment resumption – one patient had a drug interruption due to mydriasis; the mydriasis resolved but recurred a week later figure 2. resolution of teaes of special interest mydriasis urinary hesitancy/retention blurred vision discontinued resolved following drug interruption resolved without drug interruption or withdrawal 50 40 30 20 10 0 n um be r of p at ie nt s 4 7 20 10 9 5 2 8 8 patients may have had more than one teae of special interest, and ≥1 teae of special interest may have led to discontinuation. urinary hesitancy/retention includes urinary hesitation, urinary retention, urine flow decreased, dysuria, nocturia, and pollakiuria teae, treatment-emergent adverse event conclusions • in two large, phase 3, double-blind, vehicle-controlled trials, gt was well tolerated and only 3.7% (gt) and 0.4% (vehicle) of patients discontinued due to a teae • teaes were mostly mild or moderate in severity and transient • clinical management of teaes included drug interruption (6.3% gt, 2.2% vehicle) and drug reduction (5.2% gt, 0 vehicle) • anticholinergic events of blurred vision, mydriasis, and urinary hesitancy/retention occurred infrequently; when anticholinergic events did occur, onset was most often early, and most events resolved without interruption or withdrawal of gt treatment • assessment of teae management in the open-label extension trial will continue to inform clinical practice references 1. doolittle et al. arch dermatol res. 2016; 308 (10):743-9. 2. spalding et al. value health. 2003;6(3):242. 3. glaser et al. j am acad dermatol. 2018. in press. 4. glaser et al. j clin aesthet dermatol. 2018;11(5 suppl):s16-17 (abstract). acknowledgements these studies were funded by dermira, inc. medical writing support was provided by prescott medical communications group (chicago, il) with financial support from dermira, inc. disclosures dmp: consultant and investigator for dermira, inc. rg & jd: employees of dermira, inc. lg: investigator for brickell; advisory board member and investigator for dermira. darrell rigel md, ms1; mark lebwohl md1; todd schlesinger md2; april armstrong md3; brian berman md, phd4; neal bhatia md5; james del rosso do6; leon kircik md1; vishal a. patel md7; siva narayanan phd8; volker koscielny md9; ismail kasujee phd9 1mount sinai icahn school of medicine, new york, ny, usa; 2clinical research center of the carolinas, charleston, sc, usa; 3keck school of medicine, university of southern california, los angeles, ca, usa; 4university of miami miller school of medicine, miami, fl, usa; 5therapeutics clinical research, san diego, ca, usa; 6jdr dermatology research/thomas dermatology, las vegas, nv, usa; 7george washington school of medicine and health sciences, washington, dc, usa; 8avant health llc, bethesda, md, usa; 9almirall sa, barcelona, spain. impact of actinic keratosis on patient-reported ak symptoms, emotions and functioning measured using skindex-16, among patients with actinic keratosis administered tirbanibulin in real-world community practices across the u.s. (proak study) objectives: objective of the analysis is to evaluate changes in patientreported ak symptoms, emotions and functioning, among patients with aks treated with tirbanibulin in community practices across the u.s. methods: a single-arm, prospective cohort study (proak) was conducted among adult patients with aks on the face or scalp who were newly initiated with tirbanibulin treatment in real-world community practices in the u.s, as part of usual care. patients and clinicians completed surveys and clinical assessments at baseline, week-8 (timeframe for main endpoints) and week-24. skindex-16, completed at baseline and week-8, is a 16-item survey with 3 domains: symptoms (items 1-4), emotions (items 5-11) and functioning (items 12-16), with each item scored on a seven-point adjectival response scale, with a potential score of 0 (never bothered) to 6 (always bothered). changes from baseline in proportion of patients reporting a score of 0 or 1 (never or least bothered; i.e., least disease burden) was analyzed for all skindex-16 items at week-8. results: a total of 290 patients with aks completed the study assessments at week-8 (female: 31.38%; fitzpatrick skin type: i: 7.59%, ii: 71.38%, iii: 18.62%, iv: 1.38%, v: 1.03%). patient self-reported skintexture was – dry: 39.66%, smooth: 47.59%, rough: 19.66%, bumpy: 18.62%, scaly: 35.17%, blistering/peeling: 6.55%. within symptoms domain of skindex-16 related to itching, burning/stinging, hurting, and irritation, proportion of patients reporting “never or least bothered” increased significantly for each item at week-8 (p<0.0001). within emotions domain of skindex-16 related to persistence of condition, worries about skin, appearance, frustration, embarrassment, being annoyed, and feeling depressed, proportion of patients reporting “never or least bothered” increased significantly for each item at week-8 (p<0.0001). within functioning domain of skindex-16 related to interactions with others, desire to be with others, show affection, effect on daily activities, and effect on work or enjoyable activities, proportion of patients reporting “never or least bothered” increased significantly for each item at week-8 (p<0.0001). conclusion: patients with aks who used once-daily tirbanibulin treatment for 5-days reported a significant reduction in the ak burden, as indicated by the improvement in ak symptoms and emotional/functional impact, at week-8. synopsis conclusions • patients with aks who used once-daily tirbanibulin treatment for 5-days reported a significant reduction in ak burden, as indicated by the improvement in ak symptoms and emotional/functional impact, at week-8. • the demonstrated effectiveness and the safe and tolerable profile of once-daily tirbanibulin treatment highlights the benefits associated with this novel therapeutic option in routine community practice settings, for optimal management of aks. methods • a single-arm, prospective cohort study (proak) was conducted among adult patients with aks on the face or scalp who were newly initiated with once-daily tirbanibulin treatment (5-day course) in real-world community practices in the u.s, as part of usual care. • a total of 300 subjects were enrolled from 32 community practices across the u.s. • patients and clinicians completed surveys and clinical assessments at baseline, week-8 (timeframe for main endpoints) and week-24, concerning safety and effectiveness of tirbanibulin. • skindex-16, a validated pro instrument, was completed by patients at baseline and week-8. • this 16-item survey has 3 domains, namely, symptom domain (4 items), emotions domain (7 items) and functioning domain (5 items). • all items are scored on a seven-point adjectival response scale, with a potential score of 0 (never bothered) to 6 (always bothered). • changes from baseline in proportion of patients reporting a score of 0 or 1 (never or least bothered; i.e., least disease burden) was analyzed for each of the skindex-16 items at week-8. objective • actinic keratosis (ak) has been shown to negatively affect emotional functioning and skin-related quality of life of patients1. impact of tirbanibulin treatment in alleviating ak disease burden in patients with aks is not adequately understood. objective of the analysis is to evaluate changes in patient-reported ak symptoms, emotions and functioning, among patients with aks treated with tirbanibulin in community practices across the u.s. reference: 1. br j dermatol. 2013;168(2):277-283. • proak study (nct05260073) was initiated in 2022, with more than 75% of the study patients treated with tirbanibulin between april and august of 2022. • out of 300 enrolled patients, a total of 290 patients with aks completed the study assessments at week-8, and hence included in the analyses. • all patients (100%) completed their 5-day once-daily treatment course. • ten patients were not included in the week-8 analyses: 1 patient had missing data, and 9 patients were discontinued from the study due to patient voluntary withdrawal of consent or lost to follow-up. • no discontinuations were related to adverse drug reactions (adrs), and there were no serious adrs reported at week-8. results in comparison to baseline: *p<0.001. patient’s ak burden significantly reduced over the 8-week tirbanibulin treatment period, as indicated by the skindex-16 responses. 53.29% 82.35% 0.00% 100.00% baseline week 8 p ro po rti on o f p at ie nt s (n =2 89 ) reporting ‘never or least bothered’ sk1: over the past week, how often have you been bothered by itching? cfb: 29.07%* 34.15% 75.00% 0.00% 100.00% baseline week 8 p ro po rti on o f p at ie nt s (n =2 84 ) reporting ‘never or least bothered’ sk5: over the past week, how often have you been bothered by persistence/recurrence of skin condition? cfb: 40.85%* 33.10% 76.66% 0.00% 100.00% baseline week 8 p ro po rti on o f p at ie nt s (n = 28 7) reporting ‘never or least bothered’ sk6: over the past week, how often have you worried about your skin condition spreading, worsening, scarring (etc.)? cfb: 43.55%* 33.68% 75.79% 0.00% 100.00% baseline week 8 p ro po rti on o f p at ie nt s (n =2 85 ) reporting ‘never or least bothered’ sk7: over the past week, how often have you been bothered by the appearance of your skin condition? cfb: 42.10%* skindex-16 symptoms domain 55.52% 87.54% 0.00% 100.00% baseline week 8 p ro po rti on o f p at ie nt s (n =2 81 ) reporting ‘never or least bothered’ sk9: over the past week, how often have you been embarrassed by your skin? cfb: 32.02%* 39.34% 79.41% 0.00% 100.00% baseline week 8 p ro po rti on o f p at ie nt s (n =2 72 ) reporting ‘never or least bothered’ sk8: over the past week, how often have you been frustrated by your skin? cfb: 40.07%* 43.11% 78.80% 0.00% 100.00% baseline week 8 p ro po rti on o f p at ie nt s (n =2 83 ) reporting ‘never or least bothered’ sk10: over the past week, how often have you been annoyed about your skin? cfb: 35.68%* 73.52% 90.24% 0.00% 100.00% baseline week 8 p ro po rti on o f p at ie nt s (n =2 87 ) reporting ‘never or least bothered’ sk11: over the past week, how often have you been feeling depressed about your skin condition? cfb: 16.75%* skindex-16 emotions domain 77.92% 91.41% 0.00% 100.00% baseline week 8 p ro po rti on o f p at ie nt s (n =2 86 ) reporting ‘never or least bothered’ sk13: over the past week, how often has your desire to be with people been affected by your skin condition? cfb: 17.48%* 71.86% 90.91% 0.00% 100.00% baseline week 8 p ro po rti on o f p at ie nt s (n =2 86 ) reporting ‘never or least bothered’ sk12: over the past week, how often has your interactions with others been affected by your skin condition? cfb: 19.23%* 87.19% 98.22% 0.00% 100.00% baseline week 8 p ro po rti on o f p at ie nt s (n =2 81 ) reporting ‘never or least bothered’ sk14: over the past week, how often has skin condition made it hard to show affection? cfb: 11.03%%* 73.52% 91.64% 0.00% 100.00% baseline week 8 p ro po rti on o f p at ie nt s (n =2 87 ) reporting ‘never or least bothered’ sk15: over the past week, how often has your skin effected your daily activities cfb: 18.12%* 80.35% 91.93% 0.00% 100.00% baseline week 8 p ro po rti on o f p at ie nt s (n =2 85 ) reporting ‘never or least bothered’ sk16: over the past week, how often has skin condition made it hard to work or do what you enjoy? cfb: 11.75%* skindex-16 functioning domain table 1: baseline patient characteristics n=290 age, mean years [min, max] 66.30 [30.00, 90.00] gender, % femalemale 31.38 68.62 primary health insurance, % private insurance medicaid medicare uninsured 41.72 3.10 53.79 1.38 history of skin cancer, % 61.72 fitzpatrick skin type, % type i type ii type iii type iv type v 7.59 71.38 18.62 1.38 1.03 baseline patient selfreported skin-texture, % dry smooth rough bumpy scaly blistering peeling 39.66 47.59 19.66 18.62 35.17 0.34 6.21 baseline severity of skin photodamage in ak affected area, % absent mild moderate severe 1.03 21.38 56.55 20.34 table 2: site characteristics n=32 current workplace: private, office-based practice, % 100 total number of board-certified dermatologists in the clinic/practice, mean 3.53 number of patients with aks managed by the clinic in a given month, mean 136.34 number of years practicing dermatology, mean 15.66 77.51% 91.35% 0.00% 100.00% baseline week 8 p ro po rti on o f p at ie nt s (n =2 88 ) reporting ‘never or least bothered’ sk2: over the past week, how often have you been bothered by burning or stinging? cfb: 13.54%* 52.84% 84.04% 0.00% 100.00% baseline week 8 p ro po rti on o f p at ie nt s (n =2 82 ) reporting ‘never or least bothered’ sk4: over the past week, how often have you been bothered by your skin condition being irritated? cfb: 31.21%* 80.34% 94.29% 0.00% 100.00% baseline week 8 p ro po rti on o f p at ie nt s (n =2 80 ) reporting ‘never or least bothered’ sk3: over the past week, how often have you been bothered by your skin condition hurting? cfb: 13.93%* presented at fall clinical dermatology | las vegas, nevada | october 18–21, 2018. previously presented at eadv 2018 80 60 40 20 100 0 r e sp o n d e r ra te ( % ) week 60.0% 62.9% 12 16 24 32 40 48 0 16 483212week etn 50 mg bw (n=170) washout ol czp 400 mg q2w (n=35) 20 28 36 44 w a sh o u t 80 60 40 20 100 0 r e sp o n d e r ra te ( % ) week 12 16 24 32 40 4820 28 36 44 w a sh o u t 80 60 40 20 100 0 r e sp o n d e r ra te ( % ) week 12 16 24 32 40 4820 28 36 44 w a sh o u t 25.7% 51.4% 42.9% 57.1% <pasi 50 at week 12 placebo q2w (n=24) 80 60 40 20 100 0 r e sp o n d e r ra te ( % ) week 12 16 24 32 40 48 0 16 483212week etn 50 mg bw (n=170) washout czp 200 mg q2wa (n=50) 20 28 36 44 w a sh o u t 80 60 40 20 100 0 r e sp o n d e r ra te ( % ) week 12 16 24 32 40 4820 28 36 44 w a sh o u t 80 60 40 20 100 0 r e sp o n d e r ra te ( % ) week 12 16 24 32 40 4820 28 36 44 w a sh o u t 90.0% 82.0% 25.0% 8.3% 100.0% 100.0% 68.0% 78.0% 16.7% 4.2%37.5% 30.0% 80.0% 72.0% 12.5% 4.2% 50.0% 64.0% ≥pasi 75 at week 16 clinical response in plaque psoriasis patients switching from etanercept to certolizumab pegol in a phase 3, randomized, controlled study m. augustin,1 j. węgłowska,2 m. lebwohl,3 c. paul,4 v. piguet,5,6,7 h. sofen,8 a. blauvelt,9 l. peterson,10 c. arendt,11 r. rolleri10 1institute for health services research in dermatology and nursing (ivdp), university medical center hamburg-eppendorf (uke), hamburg, germany; 2niepubliczny zakład opieki zdrowotnej multimedica, wrocław, poland; 3icahn school of medicine at mount sinai, new york, ny; 4paul sabatier university, toulouse, france; 5cardiff university and university hospital of wales, cardiff, uk; 6division of dermatology, department of medicine, university of toronto, toronto, canada; 7division of dermatology, women’s college hospital, toronto, canada; 8david geffen school of medicine at ucla, los angeles, ca; 9oregon medical research center, portland, or; 10ucb pharma, raleigh, nc; 11ucb pharma, brussels, belgium references: 1. armstrong aw. et al. jama dermatol 2013;149:1180–5; 2. costa l. et al. drugs r d 2017;17:509;https://doi.org/10.1007/s40268-017-0215-7; 3. certolizumab pegol prescribing information. available at http://www.accessdata.fda.gov; 4. certolizumab pegol summary of product characteristics. available at http://www.ema.europa.eu/ema; 5. gottlieb ab. et al. j am acad dermatol 2018;79:302—14.e6; 6. lebwohl m. et al. j am acad dermatol 2018;79:266—76.e5. author contributions: substantial contributions to study conception/design, or acquisition/ analysis/interpretation of data: ma, jw, ml, cp, vp, hs, ab, lp, ca, rr; drafting of the publication, or revising it critically for important intellectual content: ma, jw, ml, cp, vp, hs, ab, lp, ca, rr; final approval of the publication: ma, jw, ml, cp, vp, hs, ab, lp, ca, rr. author disclosures: ma: abbvie, almirall, amgen, biogen, boehringer ingelheim, celgene, centocor, eli lilly, glaxosmithkline, hexal, janssen, leo pharma, medac, merck, msd, mundipharma, novartis, pfizer, sandoz, ucb pharma, xenoport; jw: amgen, celgene, coherus, dermira inc., eli lilly, galderma, janssen, leo pharma, merck, pfizer, regeneron, sandoz, ucb pharma; ml: allergan, aqua leo pharma, promius. employee of mount sinai which receives research funds from abbvie, amgen, boehringer ingelheim, celgene, eli lilly, janssen/johnson & johnson, kadmon, medimmune/astra zeneca, novartis, pfizer, valeant, vidac; cp: abbvie, almirall, amgen, boehringer ingelheim, celgene, glaxosmithkline, janssen cilag, leo pharma, eli lilly, novartis, pierre fabre, pfizer, sanofi regeneron, ucb pharma; vp: abbvie, amgen, boehringer ingelheim, celgene, dermira inc., janssen, eli lilly, medimmune, novartis, pfizer, sun pharma, ucb pharma, valeant; hs: abbvie, amgen, boehringer ingelheim, celgene, dermira inc., janssen, eli lilly, medimmune, novartis, pfizer, sun pharma, ucb pharma, valeant; ab: abbvie, aclaris, almirall, amgen, boehringer ingelheim, celgene, dermavant, dermira inc., eli lilly, genentech/ roche, glaxosmithkline, janssen, leo pharma, meiji, merck, novartis, pfizer, purdue pharma, regeneron, sandoz, sanofi genzyme, sienna pharmaceuticals, sun pharma, ucb pharma, valeant, vidac. lp, ca, rr: employees of ucb pharma. acknowledgements: the studies were funded by dermira inc. in collaboration with ucb pharma. ucb is the regulatory sponsor of certolizumab pegol in psoriasis. we thank the patients and their caregivers in addition to the investigators and their teams who contributed to this study. the authors acknowledge bartosz łukowski, msc, ucb pharma, brussels, beligum for publication coordination and amelia frizell-armitage, phd, and helen chambers, dphil, costello medical, cambridge, uk for medical writing and editorial assistance. all costs associated with development of this poster were funded by ucb pharma. objective • to assess the efficacy of certolizumab pegol in patients with moderate to severe plaque psoriasis who initially received 12 weeks of treatment with the anti-tnf etanercept. background • plaque psoriasis (pso) is an immune-mediated, inflammatory disease. • treatment options for pso include topicals, phototherapy or systemic medications (including biologics). • certolizumab pegol (czp) is a unique, fc-free, pegylated, anti-tumor necrosis factor (tnf), approved by both the fda and ema for the treatment of moderate to severe pso.3,4 • in phase 3 trials, czp has shown clinical improvements maintained over 48 weeks, and a safety profile consistent with the anti-tnf class, in adults with pso.5,6 • here, we assessed clinical outcomes in patients with moderate to severe pso who switched to czp following 12 weeks of etanercept (etn) treatment and a 4-week washout period. methods study design • patients in the ongoing phase 3 trial cimpact (nct02346240) were randomized to placebo, czp 400 mg every two weeks (q2w), czp 200 mg q2w for 16 weeks, or etn 50 mg twice weekly for 12 weeks (figure 1). • at week 16, following a 4-week washout, etn-randomized patients received treatment to week 48 according to their initial response. this analysis focuses on: – patients who did not achieve a 50% improvement from baseline in psoriasis area severity index (pasi 50) at week 12 and entered an escape arm where they received open-label czp 400 mg q2w. – patients who achieved a 75% improvement from baseline in pasi (pasi 75) at week 16 following the washout period and were re-randomized 2:1 to double-blind czp 200 mg q2w or placebo (pbo) q2w. patients • ≥18 years of age with pso for ≥6 months with pasi ≥12, ≥10% body surface area affected, physician’s global assessment (pga) ≥3 on a 5-point scale. • candidates for systemic pso therapy, phototherapy and/or photochemotherapy. • exclusion criteria: previous treatment with czp, etn or ≥2 biologics; history of primary failure to any biologic or secondary failure to >1 biologic; erythrodermic, guttate or generalized pso types; history of current, chronic or recurrent viral, bacterial or fungal infections. • etn primary non-response was defined post-hoc as failure to achieve a pasi 50 response at week 12. conclusions • patients with moderate to severe pso who did not achieve a clinical response after 12 weeks of etn therapy (<pasi 50) showed improvements following switch to czp 400 mg q2w. • the proportion of patients who did achieve a clinical response with etn therapy (≥pasi 75) was maintained or further improved following switch to czp 200 mg q2w. • czp may be an effective treatment option for patients who do not primarily respond to etn or require treatment switch. table 1. demographics and baseline characteristics bmi: body mass index; bsa: body surface area; bw: twice weekly; czp: certolizumab pegol; etn: etanercept; il: interleukin; ol: open-label; pasi: psoriasis area severity index; pga: physician’s global assessment; pso; plaque psoriasis; q2w: every two weeks; sd: standard deviation; tnf: tumor necrosis factor. all patients (n=559) etn 50 mg bw (n=170) etn → ol czp 400 mg q2w (n=35) etn → czp 200 mg q2w (n=50) etn → placebo q2w (n=24) age, years, mean (sd) 45.7 (13.3) 44.6 (14.1) 46.4 (15.4) 43.3 (12.9) 47.2 (13.5) male, n (%) 381 (68.2) 127 (74.7) 29 (82.9) 37 (74.0) 18 (75.0) bmi, kg/m2, mean (sd) 29.6 (6.4) 29.5 (6.3) 31.4 (6.3) 28.4 (4.7) 29.8 (5.7) prior biologic use, n (%) 154 (27.5) 51 (30.0) 12 (34.3) 15 (30.0) 10 (41.7) anti-tnf 21 (3.8) 8 (4.7) 0 2 (4.0) 2 (8.3) anti-il-17 122 (21.8) 41 (24.1) 11 (31.4) 13 (26.0) 7 (29.2) anti-il-12/il-23 32 (5.7) 10 (5.9) 2 (5.7) 2 (4.0) 2 (8.3) pso duration, years, mean (sd) 18.3 (12.3) 17.4 (12.0) 14.9 (10.0) 18.6 (12.8) 16.3 (14.2) pasi, mean (sd) 20.9 (8.1) 21.0 (8.2) 21.6 (8.3) 20.9 (9.0) 22.4 (7.9) bsa affected, %, mean (sd) 27.4 (15.6) 27.5 (15.5) 30.2 (15.5) 26.6 (15.8) 28.9 (16.1) pga score, n (%) 3 (moderate) 382 (68.3) 115 (67.6) 18 (51.4) 37 (74.0) 17 (70.8) 4 (severe) 177 (31.7) 55 (32.4) 17 (48.6) 13 (26.0) 7 (29.2) figure 1. cimpact study design bw: twice weekly (last dose of etn received at week 11.5); czp: certolizumab pegol; etn: etanercept; ld: 400 mg czp at weeks 0,2 and 4 or 16, 18 and 20; pasi: psoriasis area severity index; q2w: every two weeks. study assessments • patients were assessed through weeks 16–48 for: – pasi 75 – pasi 90 (≥90% reduction from baseline) – pga 0/1 (“clear” or “almost clear” with ≥2 category improvement from baseline) statistical analyses • patients who did not achieve pasi 50 at week 32 or later were treated as non-responders at subsequent time points. • missing data and patients withdrawn during weeks 16–48 were imputed as non-responders. results patient demographics and baseline characteristics • 170 patients were randomized to etn at week 0; 159 were still in the study at week 16. • 35/159 failed to achieve a pasi 50 response following 12 weeks of etn treatment and entered the open-label czp 400 mg q2w escape arm at week 16. • 77/159 patients demonstrated a pasi 75 response at week 16, 74 of whom entered the double-blind maintenance period; 50 patients were re-randomized to czp 200 mg q2w and 24 to placebo q2w. • baseline characteristics are shown in table 1. clinical response to czp in etn pasi 50 non-responders • at week 32 following 16 weeks of czp 400 mg q2w: – 60.0% of etn non-responders achieved a pasi 75 response (figure 2a) – 25.7% achieved a pasi 90 response (figure 2b) – 42.9% achieved a pga 0/1 response (figure 2c) • at week 48 (after 32 weeks of czp 400 mg q2w) these proportions were maintained or further increased (figure 2). clinical response to czp in etn pasi 75 responders • for etn responders who switched to czp 200 mg q2w at week 16: – 82.0% still achieved a pasi 75 response at week 48 (figure 3a) – the proportion of pasi 90 responders increased to week 48 (figure 3b) – the proportion achieving a pga 0/1 response remained high (figure 3c) • the pasi 75, pasi 90 and pga 0/1 responder rate declined through weeks 16–48 for etn patients who switched to placebo (figure 3). safety • no new safety signals were identified in patients who initially received etn and switched to czp treatment at week 16. 0 randomization re-randomization 16 4840 443212 36week initial treatment period (double-blind) maintenance period (double-blind) 1:3:3:3 <pasi 75 <pasi 50 – open label treatment <pasi 75 <pasi 75 <pasi 75 placebo q2w placebo q2w (n=24) czp 400 mg q4w czp 200 mg q2w (n=50) etn 50 mg bw (n=170) washout ld czp 400 mg q2w czp 400 mg q2w escape czp 400 mg q2w (n=74) ld <pasi 50 at week 12 (n=35) <pasi 50 – withdrawn ≥pasi 75 czp 200 mg q2w figure 2. clinical response in etn pasi 50 non-responders following switch to czp a) pasi 75 summary these data show that czp may be an e�ective treatment option in patients who require treatment switch from etanercept. we report patients with psoriasis who received etanercept 50 mg twice weekly for 12 weeks and subsequently switched to certolizumab pegol dosed at either 400 mg or 200 mg every two weeks. psoriasis patients treated with a biologic may require treatment switch to a second agent due to:1,2 dissatisfaction adverse events loss of e�cacy change of circumstance primary non-response 1 fab’ certolizumab pegol c) pga 0/1 non-responder imputation. etn non-response defined as failure to achieve ≥50% reduction from baseline in pasi at week 12. aczp 400 mg loading dose at weeks 16, 18 and 20. bw: twice weekly (last dose of etn received at week 11.5); czp: certolizumab pegol; etn: etanercept; ol: open-label; pasi: psoriasis area severity index; pga: physician’s global assessment; q2w: every two weeks. figure 3. clinical response in etn pasi 75 responders re-randomized to czp and placebo a) pasi 75 c) pga 0/1 placebo q2w (n=24) 80 60 40 20 100 0 r e sp o n d e r ra te ( % ) week 12 16 24 32 40 48 0 16 483212week etn 50 mg bw (n=170) washout czp 200 mg q2wa (n=50) 20 28 36 44 w a sh o u t 80 60 40 20 100 0 r e sp o n d e r ra te ( % ) week 12 16 24 32 40 4820 28 36 44 w a sh o u t 80 60 40 20 100 0 r e sp o n d e r ra te ( % ) week 12 16 24 32 40 4820 28 36 44 w a sh o u t 90.0% 82.0% 25.0% 8.3% 100.0% 100.0% 68.0% 78.0% 16.7% 4.2%37.5% 30.0% 80.0% 72.0% 12.5% 4.2% 50.0% 64.0% ≥pasi 75 at week 16 80 60 40 20 100 0 r e sp o n d e r ra te ( % ) week 60.0% 62.9% 12 16 24 32 40 48 0 16 483212week etn 50 mg bw (n=170) washout ol czp 400 mg q2w (n=35) 20 28 36 44 w a sh o u t 80 60 40 20 100 0 r e sp o n d e r ra te ( % ) week 12 16 24 32 40 4820 28 36 44 w a sh o u t 80 60 40 20 100 0 r e sp o n d e r ra te ( % ) week 12 16 24 32 40 4820 28 36 44 w a sh o u t 25.7% 51.4% 42.9% 57.1% <pasi 50 at week 12 b) pasi 90 b) pasi 90 s2010516 fcpanp 2020 simpson_without qr code.indd presented at the 5th fall clinical dermatology conference for pas & nps (fcpanp). background • atopic dermatitis (ad) is a chronic inflammatory skin condition characterized by pruritus and disruption of skin-barrier function, predominantly driven by type 2 inflammation1 • in a majority of patients with moderate-to-severe ad, circulating c-c motif chemokine ligand 17 (ccl17, also known as thymus and activation-regulated chemokine [tarc]) and total ige concentrations are elevated and correlate with disease severity2–4 • serum tarc, ige, and lactate dehydrogenase (ldh) have been suggested as biomarkers for monitoring ad disease activity and treatment response4 • dupilumab is a fully human monoclonal antibody5,6 that blocks the shared receptor component for interleukin (il)-4 and il-13, thus inhibiting signaling of both il-4 and il-13, which are key drivers of type 2 inflammation7 dupilumab decreases blood biomarkers in adolescents with moderate-to-severe atopic dermatitis: data from a phase 3 trial (liberty ad adol) eric l. simpson1, hiroyuki fujita2, kazuhiko arima2, jennifer hamilton3, yufang lu3, ana b. rossi4, ashish bansal3 1oregon health and science university, portland, or, usa; 2sanofi kk, tokyo, japan; 3regeneron pharmaceuticals, inc., tarrytown, ny, usa; 4sanofi genzyme, cambridge, ma, usa baseline demographics and disease characteristics • demographics and baseline characteristics were similar across treatment groups and showed considerable disease burden at baseline; > 90% of patients had ≥ 1 comorbid type 2 inflammatory disease including allergic rhinitis, asthma, or food allergy (table 1) • baseline blood levels of tarc, total ige, ldh, and allergen-specific ige are shown in table 2 methods study design • liberty ad adol (nct03054428) study design has been published previously8 and is summarized in figure 1 screening age ≥ 12 to < 18 years • moderate-to-severe ad • ad inadequately controlled by topical therapies • scores on iga ≥ 3, easi ≥ 16, peak pruritus nrs ≥ 4; bsa involvement ≥ 10% washout • prior medication stratification • body weight (< 60 kg or ≥ 60 kg) • iga score (3 or 4) treatment period (16 weeks) follow-up period (12 weeks)loading dose on day 1a day –35 to day –1 baseline week 28week 16 post-treatment options • open-label extension • safety follow-up through week 28 placebo (n = 85) dupilumab 300 mg sc q4w (n = 84) dupilumab 200 or 300b mg sc q2w (n = 82) r 1:1:1 figure 1. study design. afor q2w, patients with body weight < 60 kg at baseline received a loading dose of 400 mg on day 1, while patients with body weight ≥ 60 kg received a loading dose of 600 mg. all patients in every 4 weeks (q4w), regardless of weight, received a 600 mg loading dose. bpatients with body weight < 60 kg received 200 mg of the study drug; patients with body weight ≥ 60 kg received 300 mg. bsa, body surface area; easi, eczema area and severity index; iga, investigator’s global assessment; nrs, numerical rating scale; r, randomization. –140 –100 –80 –60 –40 –20 0 20 40 0 2 4 6 8 10 12 14 16 week *** *** m e d ia n ( iq r ) c h a n g e f ro m b a s e lin e in l d h c o n c e n tr a ti o n ( u /l ) –120 a –50 –30 –20 –10 0 20 0 2 4 6 8 10 12 14 16 week *** *** m e d ia n ( iq r ) % c h a n g e f ro m b a s e lin e in l d h c o n c e n tr a ti o n ( u /l ) 10 –40 b placebo dupilumab 300 mg q4w dupilumab 200/300 mg q2w figure 4. (a) median change and (b) median percent change from baseline in ldh concentration over time.a alocf method for the last post-baseline available observed status prior to rescue treatment to visit week 16 was carried forward to impute missing data. ***nominal p < 0.0001 vs placebo at weeks 4, 8, and 16. placebo dupilumab 300 mg q4w dupilumab 200/300 mg q2w –8,000 –7,000 –6,000 –5,000 –4,000 –3,000 –2,000 –1,000 0 1,000 0 2 4 6 8 10 12 14 16 week *** *** m e d ia n ( iq r ) c h a n g e f ro m b a s e lin e in t a r c c o n c e n tr a ti o n ( p g /m l ) a –100 –80 –60 –40 –20 0 20 40 0 2 4 6 8 10 12 14 16 week *** ***m e d ia n ( iq r ) % c h a n g e f ro m b a s e lin e in t a r c c o n c e n tr a ti o n ( p g /m l ) b figure 2. (a) median change and (b) median percent change from baseline in tarc concentration over time.a alast observation carried forward (locf) method for the last post-baseline available observed status prior to rescue treatment to visit week 16 was carried forward to impute missing data. ***nominal p < 0.0001 vs placebo at weeks 2, 4, 8, 12, and 16. placebo dupilumab 300 mg q4w dupilumab 200/300 mg q2w –6,000 –5,000 –4,000 –3,000 –2,000 –1,000 0 1,000 2,000 0 2 4 6 8 10 12 14 16 week *** *** m e d ia n ( iq r ) c h a n g e f ro m b a s e lin e in t o ta l i g e c o n c e n tr a ti o n ( k u /l ) a –80 –60 –40 –20 0 20 0 2 4 6 8 10 12 14 16 week *** *** m e d ia n ( iq r ) % c h a n g e f ro m b a s e lin e in t o ta l i g e c o n c e n tr a ti o n ( k u /l ) b figure 3. (a) median change and (b) median percent change from baseline in total ige concentration over time.a alocf method for the last post-baseline available observed status prior to rescue treatment to visit week 16 was carried forward to impute missing data. ***nominal p < 0.0001 vs placebo at weeks 4, 8, 12, and 16. table 1. baseline demographics and disease characteristics.a   range placebo (n = 85) dupilumab 300 mg q4w (n = 84) dupilumab 200/300 mg q2w (n = 82) age, mean (sd), years 12–17 14.5 (1.8) 14.4 (1.6) 14.5 (1.7) male, n (%) – 53 (62.4) 52 (61.9) 43 (52.4) weight, mean (sd), kg – 64.4 (21.5) 65.8 (20.1) 65.6 (24.5) duration of ad, mean (sd), years – 12.3 (3.4) 11.9 (3.2) 12.5 (3.0) patients with iga score, n (%) 0–4 3 – 39 (45.9) 38 (45.2) 39 (47.6) 4 – 46 (54.1) 46 (54.8) 43 (52.4) easi score, mean (sd) 0–72 35.5 (14.0) 35.8 (14.8) 35.3 (13.8) peak pruritus nrs score, mean (sd) 0–10 7.7 (1.6) 7.5 (1.8) 7.5 (1.5) percent bsa involvement, mean (sd) 0–100 56.4 (24.1) 56.9 (23.5) 56.0 (21.4) scorad score, mean (sd) 0–103 70.4 (13.3) 69.8 (14.1) 70.6 (13.9) cdlqi, mean (sd) 0–30 13.1 (6.7) 14.8 (7.4) 13.0 (6.2) poem score, mean (sd) 0–28 21.1 (5.4) 21.1 (5.5) 21.0 (5.0) hads score, mean (sd) 0–42 11.6 (7.8) 13.3 (8.2) 12.6 (8.0) patients with ≥ 1 concurrent allergic condition, n (%) – 78 (91.8) 73 (88.0) 79 (96.3) allergic rhinitis – 57 (67.1) 48 (57.8) 59 (72.0) asthma – 46 (54.1) 42 (50.6) 46 (56.1) food allergy – 48 (56.5) 52 (62.7) 52 (63.4) allergic conjunctivitis – 16 (18.8) 21 (25.3) 20 (24.4) hives – 22 (25.9) 28 (33.7) 22 (26.8) chronic rhinosinusitis – 7 (8.2) 6 (7.2) 6 (7.3) nasal polyps – 2 (2.4) 1 (1.2) 2 (2.4) eosinophilic esophagitis – 0 0 1 (1.2) other allergies – 62 (72.9) 53 (63.9) 58 (70.7) adata are n (%) unless otherwise specified. cdlqi, children’s dermatology life quality index; hads, hospital anxiety and depression scale; poem, patient-oriented eczema measure; scorad, scoring atopic dermatitis; sd, standard deviation. table 2. median (iqr, q1–q3) baseline concentrations of blood biomarkers. placebo (n = 85) dupilumab 300 mg q4w (n = 84) dupilumab 200/300 mg q2w (n = 82) tarc (pg/ml) 2,160.0 (1,120.0–6,000.0) 2,095.0 (1,110.0–5,350.0) 2,940.0 (974.0–7,320.0) total ige (ku/l) 3,983.0 (813.0–10,931.0) 3,482.0 (728.0–10,000.0) 3,739.5 (1,699.0–9,517.0) ldh (u/l) 259.0 (223.0–321.0) 275.5 (227.0–362.0) 277.0 (213.0–344.0) allergen-specific ige cat dander-specific ige (ku/l) 20.7 (1.4–62.3) 27.9 (3.8–72.8) 35.2 (4.7–69.2) cow’s milk-specific ige (ku/l) 0.6 (0.2–4.9) 0.5 (0.2–1.7) 0.8 (0.2–3.2) egg white-specific ige (ku/l) 0.4 (0.1–5.6) 0.7 (0.2–4.1) 0.8 (0.2–3.5) peanut-specific ige (ku/l) 3.4 (0.2–47.9) 3.5 (0.4–38.7) 6.7 (0.5–46.3) dust mite-specific ige (ku/l) 39.9 (0.5–302.0) 15.1 (1.7–93.3) 27.7 (2.0–211.5) iqr, interquartile range; q, quartile. table 3. efficacy outcomes at week 16.a,b placebo (n = 85) dupilumab 300 mg q4w (n = 84) dupilumab 200/300 mg q2w (n = 82) patients with iga 0 or 1 2 (2.4) 15 (17.9)c 20 (24.4)d patients with easi-75 7 (8.2) 32 (38.1)d 34 (41.5)d proportion of patients with ≥ 3-point improvement (reduction) in weekly average of daily peak pruritus nrs from baselinee 8/85 (9.4) 32/83 (38.6)d 40/82 (48.8)d proportion of patients with ≥ 4-point improvement (reduction) in weekly average of daily peak pruritus nrs from baseline 4/84 (4.8) 22/83 (26.5)f 30/82 (36.6)d least squares mean percent change from baseline in weekly average of daily peak pruritus nrs (se) –19.0 (4.1) –45.5 (3.5)d –47.9 (3.4)d percent bsa involvement, mean (sd)g 42.1 (25.4) 23.4 (19.9) 26.4 (25.4) least squares mean percent change from baseline in scorad (se) –17.6 (3.8) –47.5 (3.2)d –51.6 (3.2)d least squares mean change from baseline in cdlqi (se) –5.1 (0.6) –8.8 (0.5)d –8.5 (0.5)d least squares mean change from baseline in poem (se) –3.8 (1.0) –9.5 (0.9)d –10.1 (0.8)d least squares mean change from baseline in total hads (se) –2.5 (0.8) –5.2 (0.7)h –3.8 (0.7)i acoprimary outcomes were the proportion of patients with easi75 and iga score 0/1 at week 16. bdata are n (%) unless otherwise specified. cp = 0.0007 vs placebo. dp < 0.0001 vs placebo. ean improvement of ≥ 3 points from baseline in peak pruritus nrs score represents a clinically meaningful response.9,10 fp = 0.0001. gall observed data values regardless of rescue treatment use. hnominal p = 0.0133 vs placebo. inominal p = 0.2203 vs placebo. se, standard error. table 4. proportion of patients achieving normalized status in blood levels of total ige and ldh at week 16.a,b placebo (n = 80) dupilumab 300 mg q4w (n = 77) dupilumab 200/300 mg q2w (n = 77) total igec 2 (2.5) 7 (9.1)d 3 (3.9)e ldhf 4 (28.6) 16 (88.9)g 16 (88.9)h adata are in n (%). blocf method for the last post-baseline available observed status prior to rescue treatment to visit week 16 was carried forward to impute missing data. cnumber of patients evaluated were 80 in placebo group, 77 in dupilumab 300 mg q4w group, and 77 in dupilumab 200/300 q2w group. dp = 0.0681. ep = 0.6377. fnumber of patients evaluated were 14 in placebo group, 18 in dupilumab 300 mg q4w group, and 18 in dupilumab 200/300 q2w group. gp = 0.0008. hp = 0.0021. all p values are nominal. table 5. (a) median (iqr, q1–q3) change and (b) median (iqr, q1–q3) percent change in allergen-specific ige concentrations at week 16.a,b allergen placebo (n = 85) dupilumab 300 mg q4w (n = 84) dupilumab 200/300 mg q2w (n = 82) a cat dander 0.1 (–0.5, 8.9) –4.8 (–26.9, –0.6)*** –12.6 (–29.4, –1.2)*** cow’s milk 0 (–0.1, 0.2) –0.2 (–0.6, 0)*** –0.3 (–0.9, –0.1)*** egg white 0 (–0.1, 0.2) –0.3 (–1.0, 0)*** –0.2 (–1.3, 0)*** peanut 0 (–0.2, 2.9) –0.8 (–4.0, 0)*** –2.1 (–20.8, –0.2)*** dust mite 0 (–6.1, 1.8) –5 (–49.8, –0.5)*** –10.1 (–94.0, –1.0)*** b cat dander 8.9 (–10.66, 35.30) –43.16 (–58.09, –18.75)*** –45.35 (–64.57, –18.40)*** cow’s milk 0 (–17.39, 34.55) –42.18 (–60.88, –9.52)*** –47.54 (–60.61, –21.92)*** egg white 0 (–12.18, 20.00) –40.97 (–58.43, 0)*** –41.83 (–59.26, 0)*** peanut 0.19 (–11.19, 32.07) –38.75 (–57.25, 0)*** –51.81 (–64.30, –23.68)*** dust mite 0 (–14.77, 26.57) –49.83 (–58.46, –32.25)*** –51.97 (–62.87, –29.40)*** alocf method for the last post-baseline available observed status prior to rescue treatment to visit week 16 was carried forward to impute missing data. bconcentrations of allergen-specific ige reported as ku/l. ***in (a), nominal p < 0.0001 vs placebo; in (b), p < 0.0001 vs placebo. table 6. adverse events during the study treatment period.a placebo (n = 85) dupilumab 300 mg q4w (n = 83) dupilumab 200/300 mg q2w (n = 82) number of patients with teae 59 (69.4) 53 (63.9) 59 (72.0) teae leading to permanent discontinuation of study drug 1 (1.2) 0 0 serious teae 1 (1.2) 0 0 death 0 0 0 most common teaesb dermatitis atopic (pt) 21 (24.7) 15 (18.1) 15 (18.3) skin infections (adjudicated) 17 (20.0) 11 (13.3) 9 (11.0) skin infections excluding herpetic skin infections (adjudicated) 16 (18.8) 8 (9.6) 8 (9.8) upper respiratory tract infection (pt) 15 (17.6) 6 (7.2) 10 (12.2) headache (pt) 9 (10.6) 4 (4.8) 9 (11.0) conjunctivitisc 4 (4.7) 9 (10.8) 8 (9.8) nasopharyngitis (pt) 4 (4.7) 9 (10.8) 3 (3.7) infections and infestations (soc) 37 (43.5) 38 (45.8) 34 (41.5) injection-site reaction (hlt) 3 (3.5) 5 (6.0) 7 (8.5) herpes viral infections (hlt) 3 (3.5) 4 (4.8) 1 (1.2) adata are in n (%). bpts occurring in ≥ 5% of patients in any treatment group. cincludes meddra pt: atopic keratoconjunctivitis, conjunctivitis, conjunctivitis allergic, conjunctivitis bacterial, and conjunctivitis viral. hlt, meddra high level term; meddra, medical dictionary for regulatory activities; pt, meddra preferred term; soc, meddra system organ class. teae, treatment-emergent adverse event references: 1. eichenfield lf, et al. j am acad dermatol. 2014;70:338-51. 2. kakinuma t, et al. j allergy clin immunol. 2001; 107:535-41. 3. jahnz-rozyk k, et al. allergy. 2005; 60:685-8. 4. thijs jl, et al. immunol allergy clin north am. 2017; 37:51-61. 5. macdonald le, et al. proc natl acad sci u s a. 2014;111:5147-52. 6. murphy aj, et al. proc natl acad sci u s a. 2014;111:5153-8. 7. gandhi na, et al. expert rev clin immunol. 2017;13:425-37. 8. simpson el, et al. jama dermatol. in press 2019. 9. yosipovitch g, et al. br j dermatol. 2019;181:761-9. 10. yosipovitch g, et al. exp dermatol. 2018;27 suppl 2:s98. acknowledgments: data first presented at the 44th annual meeting of the japanese society for investigative dermatology (jsid); aomori, japan; november 8–10, 2019. research sponsored by sanofi and regeneron pharmaceuticals, inc. clinicaltrials.gov identifier: nct03054428 (liberty ad adol). medical writing/editorial assistance provided by raj menon, phd, of excerpta medica, funded by sanofi genzyme and regeneron pharmaceuticals, inc. disclosures: simpson el: abbvie, eli lilly, galderma, kyowa hakko kirin, leo pharma, merck, pfizer, regeneron pharmaceuticals, inc. – investigator; abbvie, boehringer ingelheim, dermavant, eli lilly, forte, incyte, leo pharma, menlo therapeutics, pfizer, pierre fabre dermo cosmétique, regeneron pharmaceuticals, inc., sanofi genzyme, valeant – consultant honoraria. fujita h, arima k: sanofi – employees, may hold stock and/or stock options in the company. hamilton j, lu y, bansal a: regeneron pharmaceuticals, inc. employees and shareholders. rossi a: sanofi genzyme – employee, may hold stock and/or stock options in the company. blood biomarker levels at week 16 safety results objective • to evaluate blood levels of type 2 inflammatory markers in patients from a randomized, placebo-controlled, double-blind, phase 3 trial of dupilumab in adolescents with moderate-tosevere ad inadequately controlled by topical therapies (liberty ad adol) conclusions • dupilumab treatment for 16 weeks resulted in a marked reduction in blood levels of multiple type 2 inflammatory biomarkers (i.e., tarc, total ige, ldh, and allergen-specific ige); these effects were accompanied by previously reported improvements in ad signs and symptoms10 efficacy outcomes at week 16 skin july 2021 1229 proof skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 426 brief article medium-sized congenital melanocytic nevus with halo phenomenon: a report of two cases antara afrin, bs1*, lori s kim, ba2*, kurt a ashack, md1,3, thomas klis, md4, michelle bain, md4 1 michigan state university college of human medicine, grand rapids, mi 2 university of illinois college of medicine, chicago, il 3 dermatology associates of west michigan, grand rapids, mi 4 department of dermatology, university of illinois at chicago college of medicine, chicago, il *these authors contributed equally to this work and are co-first authors congenital melanocytic nevi with halo phenomenon describes the spontaneous involution of congenital nevi with a surrounding area of depigmentation. although this phenomenon is rare and likely to be benign, there are reports of melanoma development either within the halo nevus or at a distant site.1 one systematic review of adult-onset halo nevi showed that there is a 1% risk of melanoma development in the first year following halo nevi diagnosis;2 however, there is very limited research following congenital halo nevi. herein, this case series describes two patients who developed a halo and complete depigmentation in pre-existing medium-sized cmn, with and without distant vitiligo. this report highlights that dermoscopy and clinical monitoring can prevent unnecessary excision in pediatric patients, but parents may still prefer surgical treatment; we review the current surgical modalities available in removal of cmn. case 1 an 8-year-old girl presented with 2-3 years of depigmentation and surface changes on a brown birthmark involving the left medial knee. initially, the depigmentation surrounded the lesion, but soon after affected the entire lesion. the patient was otherwise healthy and without any family history of cancer or autoimmune diseases. physical examination showed a 5.0 x 2.2 cm asymptomatic, depigmented patch on the left abstract congenital melanocytic nevi with halo phenomenon in children is a rare clinical finding. we report two cases of children who developed depigmentation within medium-size congenital melanocytic nevi. clinicians should be suspicious when confronted with this phenomenon due to the risk of development into malignant melanoma. herein, we review these rare cases of medium-sized halo congenital melanocytic nevi with and without associated vitiligo, with discussion on the current recommended surgical modalities in treating medium-sized cmn. introduction case presentation skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 427 medial knee with residual pink and brown papules and macules with poliosis (figure 1). dermoscopy of the lesion (figure 2) failed to identify any structures consistent with melanoma. figure 1. a pink and brown plaque on the left medial knee with surrounding and central depigmentation and poliosis figure 2. dermoscopy of depigmented patch on left medial knee showing an absent pigment network case 2 an otherwise healthy 6-year-old girl presented with a black mole on the abdomen and a white spot above her left eye. the lesion on the abdomen was present at birth and evolved as the patient grew. about 8 months prior, the mole become darker and one month later a white area developed around the periphery. about 6 months later, the patient developed an asymptomatic white patch above her left eye. physical examination showed a 2.0 cm depigmented patch on the left upper eyelid that fluoresced on woods lamp examination. on the abdomen, there was a 4.5 cm dark brown to black papillated plaque with a 1 cm rim of depigmentation (figure 3) with no clinical or dermoscopic abnormalities. the patient was diagnosed with a medium-sized cmn with halo phenomenon and an associated vitiligo patch. figure 3. dark brown irregular plaque on abdomen with a rim of depigmentation the patients presented in this case series demonstrate halo transformation of medium congenital melanocytic nevi. while acquired nevi may develop halo depigmentation before spontaneously regressing, this halo phenomenon is less commonly seen with cmn.3 the cause of halo nevi is thought to be caused by an immunologic response to nevus cells and melanocytes.4 recent discussion skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 428 literature has demonstrated some connection between the mainly cd8+t-cell mediated pathogenesis of halo nevi transformation with that of vitiligo’s anti-melanocyte response.5 a similar reactive oxidative species pathogenesis of both halo nevi phenomenon and vitiligo has been implicated by yang et al through measurements of h2o2 levels in tissues.5 the similarities in pathogenesis may explain why halo nevi are up to 10 times more common in patients with vitiligo than the general population.6 this relationship between halo nevi and vitiligo is demonstrated by the patient presented in case two. similarly, other cases involving cmn halo transformation have demonstrated distant vitiligo.7 this association may aid clinicians in educating parents of the possibility of appearance of vitiligo in patients with cmn that are undergoing the halo phenomenon. both of the cases presented here represent rare instances of medium-sized cmn which demonstrate halo phenomenon. while case one represents halo transformation of medium cmn without vitiligo, case two represents halo transformation of medium cmn with distant vitiligo. just as in these two cases, the variability between nevi demonstrating halo phenomenon has been previously studied and it is recommended that clinicians note that not all nevi with this distinction are malignant, thereby, requiring excision.8 with thorough clinical monitoring of nevi, clinicians can avoid the use of invasive procedures while caring for patients with medium-sized cmn. however, studies have shown that parents frequently choose removal of cmn due to reasons other than concern for melanoma; specifically, a study has shown that the leading reason for treatment of cmn was to reduce psychosocial difficulties (58.7%), followed by aesthetic reasons (50.4%), and to lower melanoma risk (46.3%).9 despite the side effects that surgical excision can bring, such as repigmentation and hypertrophic scarring, majority of the parents believed that a scar is more socially acceptable than a cmn. with this in mind, there are multiple surgical modalities available for the treatment of cmn, such as complete surgical excision, dermabrasion, curettage, and laser therapy. for the treatment of large-sized cmn, fresh cultured epithelial autograft (cea) after curettage or erbium:yttrium-aluminum-garnet (er:yag) ablation was found to be a novel option with high patient satisfaction and fewer side effects.10 on the other hand, less is known regarding effectiveness of surgical treatments for medium-sized cmn, and the patients satisfaction with such treatments. based on a systematic review, the most acceptable surgical treatment of a mediumsized cmn would be to excise using tissue expanders, as it was shown to have few complications and high patient satisfaction.10,11 in terms of laser therapy, qswitched ruby laser with wavelength at 694 nm was shown to be efficacious in treating medium-sized cmn as it allows for highly selective destruction of pigment-laden cells.10,12 parents are highly concerned about the psychosocial difficulties their child may face due to cmn, and may prefer surgical removal despite the low melanoma risk.9 healthcare professionals should focus on clear communication about melanoma risk, indications for surgery, and expected outcome to best support families’ decisionmaking. conclusion skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 429 conflict of interest disclosures: none funding: none corresponding author: kurt ashack md, mhs, faad dermatology associates of west michigan 1740 east paris avenue se grand rapids, mi 49546 phone: 616-949-5600 fax: 616-949-6571 email: kashack@derm-associates.com references: 1. fishman hc. malignant melanoma arising with two halo nevi. arch dermatol. 1976;112(3):407408. doi:10.1001/archderm.1976.01630270069017 2. haynes d, strunck jl, said j, et al. association between halo nevi and melanoma in adults: a multicenter retrospective case series [published online ahead of print, 2020 aug 18]. j am acad dermatol. 2020;s0190-9622(20)32449-x. doi:10.1016/j.jaad.2020.08.056 3. itin ph, lautenschlager s. acquired leukoderma in congenital pigmented nevus associated with vitiligo-like depigmentation. pediatr dermatol. 2002;19(1):73-75. doi:10.1046/j.15251470.2002.00028.x 4. zeff ra, freitag a, grin cm, grant-kels jm. the immune response in halo nevi. j am acad dermatol. 1997;37(4):620-624. doi:10.1016/s0190-9622(97)70181-6 5. yang y, li s, zhu g, et al. a similar local immune and oxidative stress phenotype in vitiligo and halo nevus. j dermatol sci. 2017;87(1):50-59. doi:10.1016/j.jdermsci.2017.03.008 6. barona mi, arrunátegui a, falabella r, alzate a. an epidemiologic case-control study in a population with vitiligo. j am acad dermatol. 1995;33(4):621-625. doi:10.1016/01909622(95)91282-7 7. kim hs, goh bk. vitiligo occurring after halo formation around congenital melanocytic nevi. pediatr dermatol. 2009;26(6):755-756. doi:10.1111/j.1525-1470.2009.01030.x 8. weyant gw, chung cg, helm kf. halo nevus: review of the literature and clinicopathologic findings. int j dermatol. 2015;54(10):e433-435. doi:10.1111/ijd.12843 9. neuhaus k, landolt m, vojvodic m, et al. surgical treatment of children and youth with congenital melanocytic nevi: selfand proxy-reported opinions. pediatr surg int. 2020;36(4):501-512. doi:10.1007/s00383-020-04633-z 10. almutairi hm, al-hothali gi. the outcome of using different surgical modalities and laser therapy in the treatment of smalland mediumsized congenital melanocytic nevi: a systematic review. int j dermatol. 2020;59(5):535-542. doi:10.1111/ijd.14727 11. ma t, fan k, li l, et al. tissue expansion in the treatment of giant congenital melanocytic nevi of the upper extremity. medicine (baltimore). 2017;96(13). doi:10.1097/md.0000000000006358 12. nelson js, kelly km. q-switched ruby laser treatment of a congenital melanocytic nevus. dermatol surg off publ am soc dermatol surg al. 1999;25(4):274-276. doi:10.1046/j.15244725.1999.08270.x 101102042_cobi_pop_pk_l1a copies of this poster obtained through this qr code are for your personal use only and may not be reproduced without permission from the authors. scan to download a reprint of this poster. copyright © 2021. all rights reserved. introduction • ad is a chronic inflammatory skin disease; patients with ad are at higher risk for other atopic comorbidities, such as allergic rhinitis1 – based on 1 study in the united states, the 1-year prevalence of allergic rhinitis among adults is 28%2 – although it is not clear whether the presence of atopic comorbidities makes ad more difficult to treat, there is an association between the presence of atopic conditions such as allergic rhinitis and more severe ad, and there is the possibility that some atopic comorbidities can lead to worsening of underlying ad3 • crisaborole ointment, 2%, is an anti-inflammatory nonsteroidal pde4 inhibitor for the treatment of patients aged ≥3 months (≥2 years outside the united states)4 with mild-tomoderate ad – initial regulatory approval was based on the results from 2 identically designed, vehicle-controlled, phase 3 clinical studies: core 1 (nct02118766) and core 2 (nct02118792)5 objective • to ascertain the efficacy and safety of crisaborole for the treatment of ad in patients with or without allergic rhinitis in a post hoc pooled analysis from the phase 3 studies core 1 and core 2 methods patients and treatment • core 1 and core 2 were identically designed, randomized, double-blind, vehiclecontrolled, phase 3, studies to compare crisaborole with vehicle in patients with ad per hanifin and rajka criteria6 who had mild-to-moderate disease per the isga and had %bsa of ≥5 (excluding the scalp) • patients were randomly assigned in a 2:1 ratio to receive crisaborole ointment, 2%, or vehicle applied twice daily to all areas affected by ad, except the scalp, for 28 days • for this post hoc analysis, patients were stratified based on their past medical history of allergic rhinitis outcomes and assessments • the isga, which is a 5-point, physician-reported scale of ad severity,5 was assessed at baseline and weekly thereafter • pruritus severity was assessed using the sps, a validated, patient-/caregiver-reported, 4-point rating scale,7 and reported twice daily (morning and evening) via electronic diary • efficacy outcomes were – proportion of patients who achieved isga success (defined as an isga of clear [0] or almost clear [1] with a ≥2-grade improvement from baseline) at day 29 – proportion who achieved isga clear (0) or almost clear (1) at day 29 – proportion who showed improvement in sps score (defined as a weekly average sps score ≤1 point with ≥1-point improvement from baseline) at week 4 • safety outcomes were teaes (both all cause and treatment related), serious aes, and aes of special interest (ie, allergic rhinitis exacerbation) results patients • in the pooled study population, 1016 patients received crisaborole and 506 received vehicle – among them, 242 were reported to have a past medical history of allergic rhinitis and 1280 did not have a past medical history of allergic rhinitis – baseline demographics and disease characteristics were generally balanced between treatment arms and between patients who did and those who did not have allergic rhinitis; however, for patients with a past medical history of allergic rhinitis, a relatively greater proportion used systemic corticosteroids, used antihistamines concurrently, and had greater mean %bsa involvement with ad lesions (table 1) efficacy and safety of crisaborole in patients with mild-to-moderate atopic dermatitis with and without comorbid allergic rhinitis jonathan m. spergel,1 michael s. blaiss,2 peter lio,3,4 aharon kessel,5,6 liza takiya,7 john l. werth,7 michael a. o’connell,7 chuanbo zang,7 michael j. cork8 1children’s hospital of philadelphia and perelman school of medicine at university of pennsylvania, philadelphia, pa, usa; 2medical college of georgia at augusta university, augusta, ga, usa; 3northwestern university feinberg school of medicine, chicago, il, usa; 4chicago integrative eczema center, chicago, il, usa; 5bnai zion medical center, haifa, israel; 6bruce and ruth rappaport faculty of medicine, technion, haifa, israel; 7pfizer inc., collegeville, pa, usa; 8sheffield dermatology research, iicd, university of sheffield, sheffield children’s hospital, sheffield, united kingdom acknowledgments editorial/medical writing support under the guidance of the authors was provided by christopher m. goodwin, phd, at apothecom, san francisco, ca, usa, and was funded by pfizer inc., new york, ny, usa, in accordance with good publication practice (gpp3) guidelines (ann intern med. 2015;163:461-464). presented at maui derm for dermatologists 2021; january 25-29, 2021 abbreviations %bsa, percentage of treatable body surface area; ad, atopic dermatitis; ae, adverse event; isga, investigator’s static global assessment; pde4, phosphodiesterase 4; pmh, past medical history; sps, severity of pruritus score; teae, treatment-emergent adverse event. references 1. dharmage sc et al. allergy. 2014;69:17-27. 2. silverberg ji. ann allergy asthma immunol. 2019;123:144-151. 3. silverberg ji. clin dermatol. 2017;35:360-366. 4. eucrisa (crisaborole) ointment, 2%, for topical use [package insert]. new york, ny: pfizer labs; april 2020. 5. paller as et al. j am acad dermatol. 2016;75:494-503.e496. 6. hanifin jm, rajka g. acta derm venereol. 1980;60:44-47. 7. yosipovitch g et al. itch. 2018;3:e13. this study was sponsored by pfizer inc. table 1. baseline demographics and disease characteristics in patients with and patients without allergic rhinitis demographic or characteristic pmh of allergic rhinitis no pmh of allergic rhinitis vehicle n=79 crisaborole n=163 vehicle n=427 crisaborole n=853 age, y mean (sd) median (min, max) 10.9 (8.5) 9.0 (2, 45) 11.7 (9.4) 10.0 (2, 59) 12.3 (12.1) 9.0 (2, 79) 12.4 (12.6) 9.0 (2, 79) female, % (n) 68.4 (54) 48.5 (79) 53.2 (227) 57.1 (487) white, % (n) 69.6 (55) 68.1 (111) 58.8 (251) 59.3 (506) %bsa mean (sd) median (min, max) 21.5 (18.2) 17.0 (5, 86) 23.4 (20.9) 15.0 (5, 95) 17.5 (17.1) 11.0 (5, 90) 17.4 (17.3) 10.0 (5, 95) isga, % (n) mild (2) moderate (3) 34.2 (27) 65.8 (52) 38.7 (63) 61.4 (100) 38.9 (166) 61.1 (261) 38.7 (330) 61.3 (523) sps, % (n) none (0) mild (1) moderate (2) severe (3) 1.3 (1) 19 (15) 36.7 (29) 29.1 (23) 5.5 (9) 21.5 (35) 32.5 (53) 32.5 (53) 4.2 (18) 24.4 (104) 32.3 (138) 26.5 (113) 3.1 (26) 22.7 (194) 32.6 (278) 29.9 (255) prior use of systemic corticosteroids,a % (n) with asthma without asthma 53.2 (42) 62.8 (27/43) 41.7 (15/36) 42.3 (69) 52.8 (38/72) 34.1 (31/91) 30.7 (131) 41.8 (41/98) 27.4 (90/329) 28.4 (242) 40.9 (76/186) 24.9 (166/667) concurrent use of antihistamines, % (n) with asthma without asthma 53.2 (42) 60.5 (26/43) 44.4 (16/36) 38.7 (63) 44.4 (32/72) 34.1 (31/91) 21.6 (92) 27.6 (27/98) 19.8 (65/329) 21.3 (182) 36.6 (68/186) 17.1 (114/667) awithin 90 days before starting study treatment. efficacy • the proportion of patients achieving isga success at day 29 was significantly greater in crisaborole-treated patients than in those receiving vehicle, regardless of past medical history of allergic rhinitis (figure 1) • similarly, a significantly greater proportion of crisaborole-treated patients achieved isga clear or almost clear at day 29 than patients given vehicle (figure 2) • improvement in sps score at week 4 occurred in significantly more crisaborolethan vehicle-treated patients, irrespective of past medical history of allergic rhinitis (figure 3) figure 1. proportion of patients who achieved isga successa at day 29 0 10 20 30 40 50 60 70 80 90 100 pmh of allergic rhinitis no pmh of allergic rhinitis p ro po rt io n of p at ie nt s, % (9 5% c i) vehicle crisaborole p=0.003 p=0.002 18.7 22.536.6 31.3 aisga success is defined as an isga of clear or almost clear with ≥2-grade improvement from baseline. figure 2. proportion of patients who achieved isga clear or almost clear at day 29 0 10 20 30 40 50 60 70 80 90 100 pmh of allergic rhinitis no pmh of allergic rhinitis p ro po rt io n of p at ie nt s, % (9 5% c i) vehicle crisaborole p<0.001 p=0.001 29.2 36.655.9 49.0 figure 3. proportion of patients who experienced improvement in spsa at week 4 0 10 20 30 40 50 60 70 80 90 100 pmh of allergic rhinitis no pmh of allergic rhinitis p ro po rt io n of p at ie nt s, % (9 5% c i) vehicle crisaborole p=0.004 p<0.001 13.0 22.430.5 37.0 aimprovement in sps defined as weekly average sps score ≤1 point with a ≥1-point improvement from baseline. safety • the safety profile was generally similar between patients with allergic rhinitis and those without allergic rhinitis • among patients with allergic rhinitis, 53 crisaborole-treated patients (32.5%) and 22 vehicle-treated patients (27.8%) experienced at least 1 all-cause teae • among crisaborole-treated patients with allergic rhinitis, 34 patients (20.9 %) experienced a mild teae, 16 patients (9.8%) experienced a moderate teae, and 3 patients (1.8%) experienced a severe teae • individual teaes were infrequent (table 2) • the most common treatment-related teae in those with allergic rhinitis and in those without allergic rhinitis (crisaborole vs vehicle) was application site pain (4.9% vs 1.3% and 4.4% vs 1.2%, respectively) • 1 crisaborole-treated patient with allergic rhinitis experienced a serious teae (pneumonia, 0.6%), and none treated with vehicle experienced a serious teae (0%); the serious teae was not considered treatment related • allergic rhinitis was reported as an ae in ≤2 patients in any group; no anaphylaxis was reported in any group table 2. most common (in >2% patients) teaes (all cause) in patients with and patients without allergic rhinitis pmh of allergic rhinitis no pmh of allergic rhinitis vehicle n=79 crisaborole n=163 vehicle n=420 crisaborole n=849 ae (all cause), % (n) application site pain upper respiratory tract infection viral upper respiratory tract infection pyrexia cough vomiting 1.3 (1) 3.8 (3) 3.8 (3) 2.5 (2) 0 0 4.9 (8) 6.1 (10) 0.6 (1) 1.2 (2) 0.6 (1) 2.5 (4) 1.2 (5) 3.3 (14) 1.9 (8) 1.4 (6) 2.1 (9) 1.2 (5) 4.4 (37) 2.8 (24) 2.9 (25) 2.6 (22) 1.8 (15) 1.5 (13) teaes of special interest, % (n) allergic rhinitis anaphylaxis 0 0 1.2 (2) 0 0.2 (1) 0 0.1 (1) 0 limitations • these post hoc analyses were not powered to detect treatment differences in allergic rhinitis subgroups • the original studies were not specifically designed to evaluate the effects of crisaborole on allergic rhinitis conclusions • regardless of whether patients have allergic rhinitis, crisaborole is effective in treating mild-to-moderate ad symptoms, including itch • the safety profile was generally similar between patients with allergic rhinitis and those without allergic rhinitis, and no new safety signals were observed • crisaborole should be considered for the management of ad in patients whether or not the patients have concurrent allergic rhinitis slisa cross-out slisa inserted text , [we did this on the other maui derm poster and the standard for schools of medicine affiliated with another insitution is to use a comma, not "at" unless the website also uses "at" in the proper name.] slisa cross-out slisa cross-out slisa inserted text , slisa inserted text conducted [change made based on your comment regarding "to compare" in a previous poster. both are actually ok, but this might sound better] slisa inserted text , slisa inserted text , slisa highlight chris: correct now as edited? the ad mention before this was determined by the janifin and rajka criteria? placement of commas accurate to show this? it wasn't the mild/moderate that was determined by hanifin/rajka, correct? (just confirming) cgoodwin sticky note picked up from job number: 150108491 cgoodwin sticky note ok cgoodwin sticky note correct as edited cgoodwin sticky note please ensure the following document specifications are met: pdf, 16:9 (landscape ratio), standard resolution size of 1920 x 1080 cgoodwin sticky note replace qr code with the one at the following location: w:\sanfrancisco\restrictedclients\anacor\projects\congresses\winter clinical 2021\allergic comorbidities allergic rhinitis encore poster\creative cgoodwin sticky note move qr code and text up and add a disclosures section here (or below acknowledgements section) text of disclosures section: jms has served as an investigator or consultant for regeneron/sanofi genzyme, celgene, allakos, novartis, and dbv technology, has served on speaker bureaus for abbot, medscape, and sanofi, and is an associate editor for the annals of allergy, asthma & immunology. msb has served as an investigator or consultant for pfizer and regeneron/sanofi genzyme. pl is a board member of the national eczema association and has served as an advisor or consultant for regeneron/sanofi genzyme, pfizer, galderma, leo, abbvie, eli lilly, la roche posay, pierre-fabre, level ex, unilever, menlo therapeutics, theraplex, intraderm, exeltis, aobiome, arbonne, amyris, bodewell, burt's bees, and kimberly clark. pl holds stock in altus labs, micreos, and yobee care, and has received honoraria from ucb, dermavant, kiniksa, verrica, realm, and johnson & johnson, as well as fees from regeneron/sanofi genzyme and pfizer. pl has served on speaker bureaus for regeneron/sanofi genzyme, pfizer, and galderma. ak has served as an investigator or consultant for pfizer, sanofi, takeda, novartis, gsk, rafa, astrazeneca, and kamada, and has received honoraria or fees from pfizer, sanofi, takeda, novartis, gsk, rafa, teva, and kamada. lt, jlw, mao, and cz are employees and stockholders of pfizer inc. mjc has served as an investigator or consultant for astellas, boots, dermavant, eli lilly, galapagos, galderma, hyphens, johnson & johnson, kymab, l'oreal, leo, menlo therapeutics, novartis, oxagen, perrigo (aco nordic), pfizer, procter & gamble, reckitt benckiser, regeneron/sanofi genzyme, and ucb pharma. cgoodwin cross-out cgoodwin inserted text presented at the 2021 winter clinical dermatology conference; january 16-24, 2021 20201214_sugarman_elderly efficacy of microencapsulated benzoyl peroxide (e-bpo) cream, 5% in elderly rosacea patients j sugarman,¹ h baldwin,² n bhatia³ 1. university of california san francisco, san francisco, ca; 2. acne treatment & research center, brooklyn, ny; 3. therapeutics research inc, san diego, ca to interact with and explore these data more intimately, please click here: https://www.solgelposters.com introduction • in a new microencapsulated formulation (e-bpo cream, 5%), the drug is entrapped in silica microcapsules. this extends drug delivery time to improve efficacy and reduce the potential for skin irritation.1 • the efficacy, safety, and tolerability of e-bpo cream, 5% were evaluated in two identical randomized, double-blind phase 3 trials which demonstrated significant superiority of e-bpo versus vehicle for percentage of patients achieving success (clear or almost clear) on the investigators global assessment (iga) and reducing the number of lesions.2 • e-bpo cream, 5% was also well tolerated with adverse events (aes) and cutaneous safety and tolerability comparable to that for vehicle.2 • the prevalence of rosacea is higher in the elderly population than the general population,3,4 but no quantitative data has been published regarding treatment efficacy on papulopustular rosacea in this subpopulation. this report summarizes results from an analysis of younger (<65 years of age) and more elderly (≥65 years old) patients who were included in the two trials of e-bpo cream, 5%. results patients • a total of 733 patients were enrolled, including 493 who were treated with e-bpo cream, 5% and 240 who received vehicle cream (vc). • there were 606 patients <65 years old who were enrolled in the trial and 127 patients who were ≥65 years of age. efficacy • the analysis indicated that e-bpo cream, 5% was significantly superior to vc for achievement of iga success and reduction in inflammatory lesions in both age groups. • results for all patients indicated that iga success was achieved in 48.3% of patients who received e-bpo cream, 5% vs 24.5% for vc. the respective values for patients <65 years of age were 45.7% and 23.8% and those for patients ≥65 years old were 60.0% and 28.1% (figure 1). • results for all patients indicated that the absolute reduction from baseline in inflammatory lesions was –19.2 for patients who received e-bpo cream, 5% vs –11.0 for vc. the respective values for patients <65 years of age were –19.6 and –11.2 and those for patients ≥65 years old were –17.5 and –10.4 (figure 2) (all p<0.001). methods patients safety and tolerability • the safety and tolerability of e-bpo cream, 5% was comparable to vc in both age groups (table 1). • 733 patients ≥18 years old with moderate or severe disease (iga grade 3 or 4, ≥15 inflammatory lesions, ≤2 nodules) were randomized (2:1) to once-daily e-bpo cream, 5% (n=493) or vehicle cream (n=240) for 12 weeks. assessments • clinical evaluations were performed at weeks 2, 4, 8, and 12. the primary efficacy endpoints were the proportion of patients with the primary measure of success: “clear” (0) or “almost clear” (1) in the iga relative to baseline at week 12 and absolute change from baseline in inflammatory lesion count at week 12. • secondary endpoints include success in both parameters at weeks 2, 4, and 8. • all analyses were carried out on the intent-to-treat population. • adverse events were also recorded and are presented for the safety population. 733 patients / ≥18 years / 12 weeks acknowledgments: the authors wish to recognize the support of robert rhoades, phd, and thomas prunty, cmpp, of aramed strategies, llc., for their editorial and scientific analysis support. their assistance was funded along with the studies represented herein, by sol-gel technologies, ltd. references: 1. erlich m, arie t, koifman n, talmon y. structure elucidation of silica-based core-shell microencapsulated drugs for topical applications by cryogenic scanning electron microscopy. j colloid interface sci. 2020;579:778-785. 2. bhatia n, werschler w, sugarman j stein gold l. efficacy and safety of microencapsulated benzoyl peroxide cream, 5% in papulopustular rosacea: results from two phase 3, vehicle-controlled trials. 2020. in submission. 3. tan j, schöfer h, araviiskaia e, audibert f, kerrouche n, berg m; rise study group. prevalence of rosacea in the general population of germany and russia the rise study. j eur acad dermatol venereol. 2016;30:428-434. 4. sinikumpu sp, jokelainen j, haarala ak, keränen mh, keinänen-kiukaanniemi s, huilaja, l. the high prevalence of skin diseases in adults aged 70 and older. j am geriatr soc. 2020; 68:2565-2571. conclusions this combined analysis of results from the two phase 3, randomized, double-blind controlled studies of e-bpo cream, 5% indicate that it was efficacious in both older and younger patients with papulopustular rosacea. figure 1. percentage of patients achieving of iga success at 12 weeks of active treatment figure 2. reductions in inflammatory lesions from baseline to 12 weeks of treatment table 1. safety summary age <65 years age ≥ 65 years event e-bpo (n=398) % vehicle (n=198) % e-bpo (n=90) % vehicle (n=36) % any treatment-emergent adverse event 19.3 17.7 24.4 11.1 any serious treatmentemergent adverse event 0 0 1.1 2.8 deaths 0 0 0 0 discontinued study drug due to a treatment-emergent adverse event 2.0 1.0 3.3 2.8 severe treatment-emergent adverse event 0.8 0 1.1 0 drug-related treatmentemergent adverse event 4.3 1.5 6.7 0 e-bpo (n=398) % vehicle (n=198) % e-bpo (n=90) % vehicle (n=36) % nasopharyngitis 2.3 2.0 3.3 0 application site pain 2.3 1.0 2.2 0 application site erythema 1.8 1.0 4.4 0 application site pruritus 1.0 0.5 2.2 0 wrist fracture 0 1.5 2.2 0 femur fracture 0 0 0 2.8 diarrhea 0 0 2.2 0 25.5% 23.8% 28.1% 0% 20% 10% 40% 30% 60% 50% age all <65 70% p er ce nt o f su bj ec ts ac hi ev in g ig a s uc ce ss a t w ee k 12 e-bpo (n= 493) vehicle (n= 240) e-bpo (n= 403) vehicle (n= 203) e-bpo (n= 90) vehicle (n= 37) 48.3% 45.7% 60.0% p<0.0001 p<0.0001 ≥65 p=0.0009 -11.0 -11.2 -10.4 age 0 -2 -4 -6 -8 -10 -12 -14 -16 -18 -20 e-bpo (n= 493) vehicle (n= 240) e-bpo vehicle (n= 403) (n= 203) e-bpo (n= 90) vehicle (n= 37) all <65 ≥65 -19.2 -19.6 -17.5 p<0.0001 p<0.0001 p=0.009 m ea n re du ct io n in in fla m m at or y le si on co un t fr om b as el in e at w ee k1 2 60% of patients ≥65 years of age achieved iga success at week 12 with e-bpo cream, 5% efficacy of microencapsulated benzoyl peroxide (e-bpo) cream, 5% in elderly rosacea patients primary • complete clearance (akclear 100), defined as a 100% reduction from baseline in the number of clinically visible ak lesions, at week 8 secondary • partial clearance (akclear 75), defined as ≥75% reduction from baseline in the number of clinically visible ak lesions, at weeks 4 and 8 • percent reduction in ak lesion count from baseline at week 8 safety • local skin responses (lsrs) and adverse events (aes), assessed by investigators on days 1 and 4, and weeks 1, 2, 4, and 8, respectively physicianand patient-reported outcomes • global photo-damage outcome assessment by investigator at week 8 • patient treatment satisfaction questionnaire for medication (tsqm) v.1.4, and cosmetic outcome at week 8 • ingenol mebutate (ingmeb; picato®) is indicated for the topical treatment of actinic keratosis (ak) in areas of skin up to 25 cm21 • two or three consecutive days of treatment with ingmeb provides clinically relevant clearance of ak lesions on the face/scalp (0.015% gel) and trunk/extremities (0.05% gel) when compared with vehicle gel;2 in addition, treatment effects of ingmeb gel are maintained long term3 • however, some patients may require treatment of ak over areas of skin larger than 25 cm2 background methods • phase iii, randomized, parallel-group, double-blind, vehicle-controlled, eight-week trial in patients with ak (figure 1) • patients were eligible if they had 5–20 clinically typical, visible and discrete ak lesions within a selected treatment area of sun-damaged skin on either the full face, full balding scalp (>25 cm2–250 cm2) or a contiguous area of (~250 cm2) on the chest table 1. baseline demographics and disease characteristics • akclear 100 (non-site-specific score) at week 8 was 21.4% (95% ci, 18.0–24.9) for ingmeb 0.027% gel vs 3.4% (95% ci, 0.7–6.1) for vehicle gel (p<0.001). efficacy at week 8 differed according to anatomical site: o for ingmeb, akclear 100 was 23.8% (95% ci, 19.7–27.8) for the face/chest (n=435) and 12.5% (95% ci, 6.4–18.6) for the scalp (n=114); respective values in the vehicle group were 3.5% (95% ci, 0.5–6.5; n=144) and 3.1% (95% ci, 0.0–9.2; n=32) • akclear 75 (non-site-specific score) at week 4 was 59.8% (95% ci, 55.7–63.9) for ingmeb 0.027% gel vs 9.2% (95% ci, 4.8–13.5) for vehicle (p<0.001, figure 2) • at week 8, akclear 75 was 59.4% (95% ci, 55.2–63.5) for ingmeb 0.027% gel vs 8.9% (95% ci, 4.6–13.2) for vehicle gel (p<0.001); both values were similar to those observed at week 4 (figure 2) conclusions • ingmeb 0.027% gel was superior to vehicle as a field treatment on full face, balding scalp or ~250 cm2 on the chest in patients with ak, although it was less efficacious for the treatment of ak on the scalp • akclear 75 and 100, and percent reduction in lesion count were similar at weeks 4 and 8, suggesting a maximal treatment effect of ingmeb by week 4 • the safety profile of ingmeb, for both lsrs and aes, was as expected • ingmeb was also associated with higher levels of patient treatment satisfaction and cosmetic outcomes compared with vehicle 1. picato® (ingenol mebutate) prescribing information https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/202833lbl.pdf. last accessed october 2017 2. lebwohl m, et al. new england journal of medicine 2012;366(11):1010–9 3. lebwohl m, et al. jama dermatol 2013;149:666–70 references figure 1. trial design • treatment-related aes (traes) were experienced by 73.8% and 9.1% of patients in the ingmeb and vehicle groups, respectively. serious aes occurred in 1.5% vs 1.1% of patients receiving ingmeb or vehicle, respectively; none were treatment related • the most frequently reported aes (occurring in ≥2% patients receiving ingmeb 0.027% gel) included application-site pain and application-site pruritus (table 2) figure 4. composite lsr profile study endpoints results • in total 729 patients were randomized to receive ingmeb 0.027% gel (n=552) or vehicle gel (n=177). the median age was 67.5, most patients were male (73.4%), all were white and 95.6% of patients had fitzpatrick skin type i–iii (table 1). median ak count at baseline was 12 (range 5–56) efficacy patient population figure 2. akclear 75 by visit • the trial was sponsored by leo pharma a/s. the authors would like to acknowledge ailsa dermody, phd, of imed comms, an ashfield company, part of udg healthcare plc for medical writing support that was funded by leo pharma in accordance with good publication practice (ggp3) guidelines acknowledgments limitations • since lsrs were observed during the study, with early onset and rapid resolution, those receiving active treatment could potentially be identified efficacy and safety of ingenol mebutate gel in field treatment of actinic keratosis on full face, balding scalp or approximately 250 cm2 on the chest: a phase iii, randomized, controlled trial c. william hanke,1 lorne albrecht,2 laerke kristine kyhl,3 thomas larsson,3 marie louise oesterdal,3 lynda spelman4 1laser and skin surgery center of indiana, indiana, usa; 2enverus medical, surrey, british columbia, canada; 3leo pharma a/s, ballerup, denmark; 4veracity clinical research, queensland, australia all randomized (n = 729) median (range) age (years) 67.5 (38-91) n % sex male 535 73.4% female 194 26.6% race white 729 100.0% ethnicity not hispanic or latino 726 99.6% hispanic or latino 3 0.4% skin type i always burns easily, never tans 138 18.9% ii always burns easily, tans minimally 359 49.2% iii burns moderately, tans gradually (light brown) 200 27.4% iv burns minimally, always tans well (moderate brown) 31 4.3% v rarely burns, tans profusely (dark brown) 1 0.1% ingmeb 0.027% (n=549) vehicle (n=176) general disorders and administration-site conditions application-site pain 350 63.8% 4 2.3% application-site pruritus 202 36.8% 7 4.0% application-site discomfort 28 5.1% 2 1.1% application-site paresthesia 14 2.6% 2 1.1% nervous system disorders headache 22 4.0% 4 2.3% eye disorders eyelid edema 14 2.6% 0 0.0% study objective • to compare the efficacy and safety of ingmeb 0.027% gel with vehicle gel, as a field treatment in patients with ak, when applied once daily for three consecutive days on the full face, balding scalp or ~250 cm2 on the chest (clinical trial identifier: nct02361216) safety • mean composite lsr scores peaked at day 4 (ingmeb 0.027% gel, 10.8; vehicle, 1.6), rapidly declined and returned to minimal levels by week 4 (figure 4) • the lower efficacy of ingmeb observed on the scalp vs face/chest corresponded with lower lsr scores in this area o mean lsr scores for face, chest and scalp groups were 11.7, 9.5 and 8.8, respectively figure 3. reduction in ak lesion count by visit table 2. most frequent aes figure 5. tsqm scores physicianand patient-reported outcomes • investigators reported that 80% of patients receiving ingmeb experienced minor, moderate or marked improvements in the global photo-damage outcome at week 8, vs 18% in the vehicle group • tsqm global satisfaction score, driven by patients’ perceptions of effectiveness, was significantly higher for ingmeb vs vehicle (41.0-point difference; p<0.001, figure 5). no differences were reported for the side effects or convenience domains aes were classified according to meddra version 15.1 • cosmetic outcomes: o overall feel: ‘much improved’ or ‘somewhat improved’ reported by 92% patients receiving ingmeb vs 18% for vehicle o overall appearance: ‘much improved’ or ‘somewhat improved’ reported by 94% patients receiving ingmeb vs 19% for vehicle o for ingmeb, akclear 75 was 63.4% (95% ci, 58.8–67.9) for the face/chest (n=435) and 44.1% (95% ci, 35.0–53.3) for the scalp (n=114) at week 8; respective values in the vehicle group were 9.5% (95% ci,4.6–14.4; n=144) and 6.3% (95% ci, 0.0–14.7; n=32). the breakdown by anatomical location at week 4 was similar to these week 8 values • reduction in ak lesion count from baseline at week 8 with ingmeb was 75.7% (95% ci, 73.9–77.3) vs 12.7% (95% ci, 3.0–21.4) with vehicle. a similar effect was observed at week 4 (figure 3) o for ingmeb, reduction in ak lesion count from baseline at week 8 was 76.8% (95% ci, 74.7–78.6) for the face/chest (n=435) and 64.3% (95% ci, 59.1–68.8) for the scalp (n=114); respective values in the vehicle group were 15.5% (95% ci, 3.4–26.1; n=144) and 8.2% (95% ci, -14.9–26.6; n=32) placeholder for figure 1 d, day; w, week; mo, month ingmeb 0.027% gel vehicle gel treatment period follow-up period 552 patients 177 patients 1d 4d 1w 2wtime visit no. 1 4w 8w 5mo 8mo 11mo 14mo 2 3 4 5 6 7 8 9 10 11 screening period extended follow-up period ingmeb 0.027% gel vehicle gel lsr assessment ak lesion count pcg-workstation-2 sticky note marked set by pcg-workstation-2 acknowledgements: medical writing support was provided by prescott medical communications group (chicago, il) with financial support from ortho dermatologics; ortho dermatologics is a division of bausch health us, llc • presented at winter clinical 2021 • january 16-24, 2021 • virtual synopsis � combining tazarotene (taz) with a potent-to-superpotent topical corticosteroid, such as halobetasol propionate (hp), is recommended for the treatment of patients with mild-tomoderate psoriasis1 � the taz + hp combination may provide synergistic efficacy, increase the duration of remission, and reduce side effects of both hp and taz when used alone1-3 � a once-daily, fixed-combination hp 0.01%/taz 0.045% lotion (duobrii,® ortho dermatologics) was developed utilizing polymeric emulsion technology, which allows for rapid and uniform distribution of hp and taz, humectants, and moisturizers on the skin � hp/taz lotion has demonstrated efficacy and safety in patients with moderate-to-severe psoriasis,4,5 including those with lower body surface area (bsa) involvement6 objective � to evaluate efficacy and safety of hp 0.01%/taz 0.045% lotion in patients with either mild scaling or mild plaque elevation at baseline methods � in two phase 3, double-blind studies (nct02462070, nct02462122), adult participants were randomized 2:1 to hp/taz or vehicle lotion once daily for 8 weeks, with a 4-week posttreatment follow-up4,5 • participants were required to have an investigator’s global assessment (iga) score of 3 (moderate) or 4 (severe) and affected bsa of 3 to 12% at baseline • in these studies, cerave® hydrating cleanser and cerave® moisturizing lotion (l’oreal, ny) were provided as needed for optimal moisturization/cleaning of the skin � efficacy measures included treatment success (percentage of participants with ≥2-grade reduction in iga score and a score of 0 [clear] or 1 [almost clear]), change in affected bsa, and percentage of participants with ≥2-grade improvements from baseline (success) in erythema, plaque elevation, and scaling � treatment-emergent adverse events (teaes) were evaluated � pooled, post hoc analyses were performed in subsets of patients with either mild scaling (score of 2) or mild plaque elevation (score of 2) at baseline results demographics and baseline characteristics � of 418 study participants included in the overall population, 58 had mild scaling at baseline and 44 had mild plaque elevation at baseline � participant demographics and characteristics were generally similar across the groups, though there was a higher proportion of males in the mild scaling group and more participants in the mild scaling and plaque elevation groups had moderate iga at baseline (table 1) efficacy � compared with vehicle, hp/taz-treated participants in the mild scaling group had significantly greater reductions from baseline in affected bsa (figure 1), higher rates of treatment success (figure 2), and improvements in signs of psoriasis (figure 3) at week 8 � similar results were observed in the overall population (hp/taz vs vehicle at week 8: bsa reduction: -37.6% vs -3.1%; treatment success: 40.6% vs 9.9%; erythema success: 47.0% vs 14.5%; plaque elevation success: 59.6% vs 19.7%; scaling success: 61.2% vs 20.9% [p<0.001 for all])5 figure 2. treatment successa in mild plaque elevation and mild scaling subgroups (itt population, pooled) p e rc e n ta g e o f p a rt ic ip a n ts 0% 70% 0 2 4 6 8 12 study visit (weeks) treatment posttreatment 10% 20% 30% 40% ** ** ** hp/taz lotion: mild plaque elevation subgroup (n=30) hp/taz lotion: mild scaling subgroup (n=36) vehicle lotion: mild plaque elevation subgroup (n=14) vehicle lotion: mild scaling subgroup (n=22) 50% 60% * * *p<0.05; **p≤0.01 vs vehicle. adefined as ≥2-grade improvement from baseline iga and a score of “clear” or “almost clear.” hp/taz, halobetasol propionate 0.01% and tazarotene 0.045%; iga, investigator’s global assessment; itt, intent to treat. figure 3. erythema, plaque elevation, and scaling successa in mild plaque elevation and mild scaling subgroups at week 8 (itt population, pooled) p e rc e n ta g e o f p a rt ic ip a n ts 0% 100% erythema success * 61.5% 20% 40% 60% 80% 38.8% ** 50.8% 10.4% plaque elevation success * 43.1% 8.2% ** 66.6% 19.4% scaling success * 72.5% 39.2% ** 32.0% 10.2% hp/taz lotion: mild plaque elevation subgroup (n=30) hp/taz lotion: mild scaling subgroup (n=36) vehicle lotion: mild plaque elevation subgroup (n=14) vehicle lotion: mild scaling subgroup (n=22) *p<0.05; **p<0.01 vs vehicle. afor each sign of psoriasis, success defined as ≥2-grade improvement from baseline. hp/taz, halobetasol propionate 0.01% and tazarotene 0.045%; itt, intent to treat. clinical commentary � unlike real-world use, participants in this study were required to continue administration of hp/taz for 8 continuous weeks—even if they had clearance of active psoriasis—which may have contributed to increased levels of irritation in the mild subgroups versus the overall population � treatment-emergent irritation may potentially be addressed in the clinic by: • recommending that patients temporarily interrupt drug use (eg, drug holiday) and resume application of the lotion once irritation signs/ symptoms have subsided • encouraging the use of moisturizers before resuming treatment halobetasol propionate 0.01%/tazarotene 0.045% lotion for the treatment of plaque psoriasis in patients with mild scaling and mild plaque elevation � in the mild plaque elevation group, those treated with hp/taz demonstrated significantly greater improvements in signs of psoriasis at week 8 versus vehicle (figure 3) • a numerically higher treatment success rate was observed with hp/taz versus vehicle at week 8 in the mild plaque elevation group, with significance reached 4 weeks posttreatment (figure 2) • lack of statistical separation of hp/taz from vehicle for treatment success and bsa reduction may be partly attributed to the small population and/or favorable response to the vehicle formulation figure 1. bsa reduction in mild plaque elevation and mild scaling subgroups (itt population, pooled) m e a n c h a n g e f ro m b a se lin e -60% 40% 0 2 4 6 8 12 study visit (weeks) treatment posttreatment -40% -20% 0% 20% ** *** ** * hp/taz lotion: mild plaque elevation subgroup (n=30) hp/taz lotion: mild scaling subgroup (n=36) vehicle lotion: mild plaque elevation subgroup (n=14) vehicle lotion: mild scaling subgroup (n=22) *p<0.05; **p<0.01; ***p<0.001 vs vehicle. no imputation of missing data. n values shown for baseline only. bsa, body surface area; hp/taz, halobetasol propionate 0.01% and tazarotene 0.045%; itt, intent to treat. table 1. participant demographics and baseline characteristics mild scaling (n=58) mild plaque elevation (n=44) overall population (n=418) age, mean, y 52.1 49.8 50.3 males, n (%) 40 (69.0) 25 (56.8) 272 (65.1) white race, n (%) 49 (84.5) 38 (86.4) 358 (85.6) iga of 3 (moderate)a 55 (94.8) 43 (97.7) 356 (85.2) bsa, mean, % 5.5 4.8 5.9 erythema 2 – mild 0 0 36 (8.6) 3 – moderate 51 (87.9) 44 (100) 331 (79.2) 4 – severe 7 (12.1) 0 51 (12.2) plaque elevation 2 – mild 0 44 (100) 44 (10.5) 3 – moderate 57 (98.3) 0 320 (76.6) 4 – severe 1 (1.7) 0 54 (12.9) scaling 2 – mild 58 (100) 0 58 (13.9) 3 – moderate 0 43 (97.7) 303 (72.5) 4 – severe 0 1 (2.3) 57 (13.6) aall other participants had an iga score of 4 (severe) at baseline. bsa, body surface area; iga, investigator’s global assessment. safety � treatment-emergent adverse events occurred at generally similar rates in each subgroup and the overall population, and most were mild to moderate in severity (table 2) � rates of contact dermatitis were higher in the hp/taz-treated mild scaling and plaque elevation subgroups versus the overall population (table 2) � skin atrophy was reported as an adverse event in only 1 participant who received hp/taz lotion in the mild scaling group table 2. treatment-emergent adverse events through week 8 mild scaling mild plaque elevation overall population hp/taz lotion (n=35) vehicle lotion (n=22) hp/taz lotion (n=29) vehicle lotion (n=14) hp/taz lotion (n=270) vehicle lotion (n=140) any teae, n (%) 14 (40.0) 7 (31.8) 12 (41.4) 3 (21.4) 97 (35.9) 30 (21.4) treatment-related teaes, n (%) 9 (25.7) 3 (13.6) 10 (34.5) 2 (14.3) 55 (20.4) 11 (7.9) intensity of treatment-related teaes, n (%) mild 3 (8.6) 0 3 (10.3) 2 (14.3) 20 (7.4) 3 (2.1) moderate 5 (14.3) 2 (9.1) 5 (17.2) 0 26 (9.6) 6 (4.3) severe 1 (2.9) 1 (4.5) 2 (6.9) 0 9 (3.3) 2 (1.4) most common teaesa, n (%) contact dermatitis 4 (11.4) 0 5 (17.2) 0 20 (7.4) 0 pruritus 2 (5.7) 1 (4.5) 1 (3.4) 1 (7.1) 8 (3.0) 4 (2.9) pain of skin 0 0 0 1 (7.1) 0 1 (0.7) excoriation 3 (8.6) 0 0 0 5 (1.9) 0 folliculitis 0 0 4 (13.8) 0 5 (1.9) 0 burning sensationb 0 0 2 (6.9) 1 (7.1) 4 (1.5) 3 (2.1) aat least 5% incidence in any treatment group; does not include 3 aes in which each event was deemed unrelated to treatment (sinusitis, nasopharyngitis, and nausea). bsystem organ class: nervous system disorder. ae, adverse event; hp/taz, halobetasol propionate 0.01% and tazarotene 0.045%; teae, treatment-emergent adverse event. conclusions � in two pooled phase 3 studies, hp 0.01%/taz 0.045% lotion was efficacious and well tolerated following 8 weeks of treatment among participants with mild plaque elevation and mild scaling � results were generally similar to the overall study population, indicating that hp/taz lotion is a viable treatment option for patients with plaque psoriasis who have mild signs of scaling and plaque elevation, regardless of their iga severity at baseline references 1. elmets ca, et al. j am acad dermatol. online ahead of print, 2020 jul 30. doi:10.1016/j. jaad.2020.07.087. 2. tanghetti e, et al. j dermatolog treat. 2019:1-8. 3. kircik lh, et al. j drugs dermatol. 2019;18(3):279-284. 4. stein gold l, et al. j am acad dermatol. 2018;79(2):287-293. 5. sugarman jl, et al. j drugs dermatol. 2018;17(8):855-861. 6. leonardi c, et al. poster virtually presented at fall clinical 2020. author disclosures lsg has served as investigator/consultant or speaker for ortho dermatologics, leo pharma, dermavant, incyte, novartis, abbvie, pfizer, sun pharma, ucb, arcutis and lilly; et has served as speaker for novartis, ortho dermatologics, sun pharma, lilly, galderma, abbvie, and dermira; served as a consultant/clinical studies for hologic, ortho dermatologics, and galderma; and is a stockholder for accure; cl is a consultant for abbvie, amgen, boehringer ingelheim, dermira, eli lilly, janssen, leo pharma, pfizer, sandoz, ucb, and vitae; an investigator for actavis, abbvie, allergan, amgen, boehringer ingelheim, celgene, coherus, cellceutix, corrona, dermira, eli lilly, galderma, glenmark, janssen, leo pharma, merck, novartis, novella, pfizer, sandoz, sienna, stiefel, ucb, and wyeth; and a speaker for abbvie, celgene, novartis, sun pharma, and eli lilly; sk is an advisory board member/consultant for abbvie, galderma, incyte corporation, pfizer inc., regeneron pharmaceuticals, and kiniksa pharmaceuticals and has received grant funding from galderma, pfizer inc. and kiniksa pharmaceuticals; aj is an employee of ortho dermatologics and may hold stock and/or stock options in its parent company. linda stein gold, md1; emil a tanghetti, md2; craig leonardi, md3; shawn g kwatra, md4; abby jacobson, ms, pa-c5 1henry ford hospital, detroit, mi; 2center for dermatology and laser surgery, sacramento, ca; 3department of dermatology, st. louis university medical school, st. louis, mo; 4department of dermatology, johns hopkins university school of medicine, baltimore, md; 5ortho dermatologics*, bridgewater, nj *ortho dermatologics is a division of bausch health us, llc. figure 4. overview of teaes through week 8. hp, halobetasol propionate; teae, treatment-emergent adverse event. figure 3. affected bsa reduction (a) and treatment success (b) at week 8. ***p<0.001 vs vehicle. bsa, body surface area; hp, halobetasol propionate; iga, investigator’s global assessment. ano imputation of missing data. bdefined as ≥2-grade reduction from baseline in iga score and a score of “clear” or “almost clear.” values have been adjusted for multiple imputation. • treatment-related teaes with hp 0.01% lotion were local application site reactions, none of which occurred in more than 2 participants ( table 1) table 1. treatment-related teaes through week 8 • there were no teae reports of skin atrophy or folliculitis with hp treatment; there was 1 teae of telangiectasia in the hp lotion group that was deemed unrelated to treatment results epidermal permeation (in vitro) • hp 0.01% lotion demonstrated superior permeation efficiency over 0.05% cream, with a >3.5-fold higher percentage of the applied dose measured in the epidermis (figure 2) figure 2. epidermal levels of hp following 24 hours of topical exposure. mean of 10 tissue samples shown. hp, halobetasol propionate. phase 3 studies efficacy • in the phase 3 studies, 430 adults were randomized to hp lotion (n=285) or vehicle lotion (n=145) • hp 0.01% lotion was statistically superior to vehicle at week 8 in percent reduction from baseline in affected bsa and percentage of participants achieving treatment success (figure 3) adverse events • rates of teaes through week 8 were similar for participants treated with hp 0.01% lotion and those treated with vehicle, as were teae severity and incidence of treatment-related teaes (figure 4) objective • to summarize the in vitro epidermal permeation of halobetasol propionate (hp) 0.01% lotion and its clinical efficacy and safety in participants with plaque psoriasis conclusion • a low-concentration hp 0.01% lotion formulation demonstrated >3.5-fold higher epidermal penetration of the active ingredient than hp 0.05% cream – the polymeric emulsion 0.01% lotion formulation allows for more effective delivery of hp, even at one-fifth the concentration of hp 0.05% cream • hp 0.01% lotion was more efficacious than vehicle in the treatment of moderate-to-severe plaque psoriasis, had a favorable safety profile over 8 weeks of oncedaily use, and led to no treatment-emergent adverse event (teae) reports of skin atrophy or folliculitis • once-daily hp 0.01% lotion is an efficacious and safe option for psoriasis treatment beyond the 2 to 4 weeks of continuous use recommended for other topical corticosteroids synopsis • topical corticosteroids are the mainstay of psoriasis treatment and can be used as monotherapy or in combination with other treatments1 • however, the use of superpotent topical corticosteroids, such as hp, is generally limited to 2 to 4 weeks as monotherapy to mitigate the risk of cutaneous side effects1,2 • a lower-dose formulation of hp 0.01% lotion was developed using polymeric emulsion technology, which allows for up to 8 weeks of continuous once-daily use (figure 1) figure 1. polymeric emulsion lotion technology. methods percutaneous absorption study • epidermal deposition of hp 0.01% lotion and hp 0.05% cream was compared in an in vitro percutaneous permeation study • approximately 5 mg/cm2 of each formulation (clinically relevant dose) was applied to dermatomed cadaveric human tissue from 1 female donor • after 24 hours, hp concentrations were determined with liquid chromatography–mass spectrometry phase 3 studies • in two phase 3 randomized, double-blind, vehicle-controlled studies (nct02514577, nct02515097), adult participants with psoriasis were randomized (2:1) to receive hp 0.01% or vehicle lotion once daily for 8 weeks, with a 4-week posttreatment follow-up3 – at baseline, participants were required to have an investigator’s global assessment (iga) score of 3 (moderate) or 4 (severe) and affected body surface area (bsa) of 3% to 12% – in these studies, cerave® hydrating cleanser and cerave® moisturizing lotion (l’oreal, ny) were provided as needed for optimal cleaning/ moisturizing of the skin • data from the 2 studies were pooled for analysis; efficacy assessments included treatment success (percentage of participants with ≥2-grade reduction in iga score and a score of 0 [clear] or 1 [almost clear]) and reduction in affected bsa • safety and tolerability assessments included teaes halobetasol propionate 0.01% lotion for plaque psoriasis: epidermal permeation, efficacy, and safety lawrence green, md1; jerry bagel, md2; george han, md, phd3; abby jacobson, ms, pa-c4; martha l. sikes, dmsc, ms, rph, pa-c4 1department of dermatology, george washington university school of medicine, washington, dc; 2psoriasis treatment center of central new jersey, east windsor, nj; 3icahn school of medicine at mount sinai, new york, ny; 4ortho dermatologics, bridgewater, nj presented at winter clinical dermatology conference® • january 13-18, 2023 • kohala coast, hi sponsored by ortho dermatologics, a division of bausch health us, llc. 1-2 µm 3-d mesh allows for uniform distribution of halobetasol propionate and moisturizing agents droplets consisting of halobetasol propionate and oil-soluble moisturizing agents held apart by the 3-d mesh 25-50 µm 3-d mesh (polymeric matrix) holding water and water-soluble hydrating agents within the mesh 6.17 1.72 0 2 4 6 8 10 hp 0.01% lotion hp 0.05% cream pe rc en t o f a pp lie d do se , m ea n teae rate hp 0.01% lotion n=284 n=142 of participants with teaes: 11.7 9.8 35.2 40.9 52.9 49.1 vehicle lotion hp 0.01% 0% 20% 40% 60% 80% 100% severe moderate mild 21.5% vehicle lotion23.9% maximum teae severity vs n=34 n=61 yes yes no no vehicle lotion hp 0.01% 0% 20% 40% 60% 80% 100% n=61 n=34 related to treatment -35.2 -5.9 -50 -40 -30 -20 -10 0 hp lotion (n=265) vehicle lotion (n=131) *** *** 37.4 10.0 0 10 20 30 40 50 hp lotion (n=285) vehicle lotion (n=145) pa rt ic ip an ts , % m ea n ch an ge fr o m b as el in e, % a. bsaa b. treatment successb acknowledgments: medical writing support was provided by medthink scicom (cary, nc) with financial support from ortho dermatologics; ortho dermatologics is a division of bausch health us, llc. disclosures: lg has served as a consultant, speaker, and/or investigator for abbvie, amgen, arcutis, celgene, dermavant, jannsen, lilly, mc2, novartis, ortho dermatologics, sienna, sun pharma, and ucb. jb is an investigator and speaker for ortho dermatologics. gh is or has been an investigator, consultant/advisor, or speaker for abbvie, athenex, boehringer ingelheim, bond avillion, bristol-myers squibb, celgene, eli lilly, janssen, leo pharma, mc2, novartis, ortho dermatologics, pellepharm, pfizer, regeneron, sanofi genzyme, sun pharma, and ucb. ab and mls are employees of ortho dermatologics and may hold stock and/or stock options in its parent company. prior presentation: data in this poster were previously presented at the winter clinical dermatology conference; january 16-24, 2021; virtual. references: 1. elmets et al. j am acad dermatol. 2021;84:432-470. 2. bagel et al. cutis. 2020;105:92-96;e94. 3. sugarman et al. cutis. 2019;103:111-116. presenting author: lawrence green, md; drgreen@looking-younger.com teaes, n (%) hp 0.01% lotion (n=284) vehicle lotion (n=142) application-site dermatitis 2 (0.7) 0 application-site pruritus 1 (0.4) 1 (0.71) application-site infection 1 (0.4) 0 application-site discoloration 1 (0.4) 0 application-site pain 0 2 (1.4) psoriasis 0 1 (0.7) application-site cellulitis 0 1 (0.7) application-site abscess 0 1 (0.7) hp, halobetasol propionate; teae, treatment-emergent adverse event. skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 120 rising derm stars® pilot study of use of neural network for quantitative before-and-after analysis of dermatologic cosmetic procedures adam aronson, md1, anastasia georgievskaya, hillary jahangir-johnson, md, ksenia guseva 1department of dermatology, university of iowa, iowa city, ia background/objectives: in dermatologic cosmetic procedures, quantitative measures of efficacy have historically been lacking. before and after pictures provide an illustration of the effects of a procedure, but are often cherrypicked to show best outcomes rather than typical outcomes and are inherently subjective. attempts to apply statistic analysis regarding degree of cosmetic improvement typically relies on various assessment scales, in which various metrics are subjectively graded on a likert scale by two or more blinded scorers, and numerable results are then reconciled and statistical analysis is performed1,2,3. these methods are time-consuming and may require multiple revisions to attain acceptable interand intrarater reliability, which decreases study objectivity. methods: here, we present an ongoing pilot study exploring potential for deep learning neural networks to perform visual facial analysis both before and after dermatologic cosmetic procedures, with the goal of creating a more accurate and reproduceable understanding of which facial characteristics are affected by the procedure. youth laboratories (ylabs.ai) has developed and trained a neural network for evaluation of skin parameters with the goal of analyzing skin health and disease biomarkers. an earlier version of this software was publicly available as a downloadable application called rynkl. this software has since been updated to tailor it to this project. it currently tracks parameters including skin evenness, redness, sebum, porphyrins, skintone, pore characteristics, and estimated age (figure 1). in theory, this technology should be useful for measuring efficacy of almost any facial cosmetic procedure after appropriate validation. in the pilot study, we are focusing on full facial resurfacing procedures with co2re laser. patients electively choosing to undergo this procedure are identified preprocedure and consent is obtained for photography and software analysis of images. at this time, enrollment is limited to caucasian females, as the neural network currently has the most reference images for this demographic. high resolution facial photographs are obtained prior to procedure and at 3 months post-procedure. all of the above-listed parameters are numerically rated by the rynkl software, with the goal of determining which quantitative differences, if any, are measurable after healing from the procedure. following collection of all before and after photographs, four blinded dermatology residents will also score each photograph for the same parameters for comparison of reliability between trained scorers and neural network. photograph and data collection is ongoing at the time of this writing. skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 121 discussion: though neural networks have not been trained for this purpose previously, they are not entirely new to dermatology. neural networks have already been trained to be comparable to board-certified dermatologists in the identification of skin cancers4. though this study is still in the proof of concept phase, neural networks by their nature improve incrementally with each new image fed to them and thus become more powerful every day. the use of neural networks for improving the depth of dermatologic research is one of many developing usages. figure 1: references: 1. idriss n and maibach hi. scar assessment scales: a dermatologic overview. skin res technol. 2009 feb;15(1):1-5. pmid: 19152571 2. carruthers a and carruthers j. a validated facial grading scale: the future of facial ageing measurement tools? j cosmet laser ther. 2010 oct;12(5):235-41. pmid: 20825260 3. narins rs et al. validated assessment scales for the lower face. dermatol surg. 2012 feb;38(2 spec no.):333-42. pmid: 22316189 4. esteva a et al. dermatologist-level classification of skin cancer with deep neural networks. nature. 2017;542(7639):115-118. pmid: 28117445 skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 506 original research development and validation of a diagnostic 35-gene expression profile test for ambiguous or difficult-to-diagnose suspicious pigmented skin lesions sarah i. estrada, md1, jeffrey b. shackelton, md2, nathan j. cleaver, do3, natalie d. depciksmith, md4, clay j. cockerell, md5, stephen n. lencioni, bs2, howard l. martin, md6, jeffrey wilkinson, phd7, lauren meldi sholl, ms7, michael d. berg, phd7, brooke h. russell, phd7, olga zolochevska, phd7, kyle r. covington, phd7, aaron s. farberg, md8, matthew s. goldberg, md7,9, pedram gerami, md 10, gregory a. hosler, md, phd11 1affiliated dermatology, scottsdale, az. 2skin cancer and dermatology institute, reno, nv. 3cleaver medical group, cumming, ga. 4aurora diagnostics gpa laboratories, greensboro, nc. 5cockerell dermatopathology, dallas, tx. 6sagis, houston, tx. 7castle biosciences, inc., friendswood, tx. 8baylor university medical center, dallas, tx. 9icahn school of medicine, mount sinai, ny. 10northwestern university, chicago, il. 11propath, dallas, tx. abstract purpose: a clinical hurdle for dermatopathology is the accurate diagnosis of melanocytic neoplasms. while histopathologic assessment is frequently sufficient, high rates of diagnostic discordance are reported. the development and validation of a 35-gene expression profile (35-gep) test that accurately differentiates benign and malignant pigmented lesions is described. methods: lesion samples were reviewed by at least three independent dermatopathologists and included in the study if 2/3 or 3/3 diagnoses were concordant. diagnostic utility of 76 genes was assessed with quantitative rt-pcr; neural network modeling and cross-validation were utilized for diagnostic gene selection using 200 benign nevi and 216 melanomas for training. to reflect the complex biology of melanocytic neoplasia, the 35-gep test was developed to include an intermediaterisk zone. results: validation of the 35-gep was performed in an independent set of 273 benign and 230 malignant lesions. the test demonstrated 99.1% sensitivity, 94.3% specificity, 93.6% positive predictive value and 99.2% negative predictive value. 96.4% of cases received a differential result and 3.6% had intermediate-risk. conclusions: the 35-gep test was developed to refine diagnoses of melanocytic neoplasms by providing clinicians with an objective tool. a test with these accuracy metrics could alleviate uncertainty in difficult-to-diagnose lesions leading to decreased unnecessary procedures while appropriately identifying at-risk patients. skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 507 over 5 million skin biopsies are performed annually in the us, leading to the diagnosis of over 130,000 invasive melanomas.1–5 because melanoma is one of the most aggressive skin cancers, early detection and diagnosis are crucial.1,6 current methods used for definitive diagnosis of melanoma are sufficient for the majority of lesions; however, histopathologic assessment can be challenging, even for experienced dermatopathologists, and high rates of diagnostic discordance have been reported.7–11 even pigmented lesions with clear pathological features consistent with benign nevi or invasive melanoma have concordance rates of 92% and 72%, respectively7, indicating that a subset of lesions with typical histopathological presentation are subject to differential assessment. visual assessment of hematoxylin and eosin (h&e) stained lesions is inherently subjective and relies on expert interpretation and integration of a wide spectrum of architectural and cytologic features that are weighted differently based on the presumed subtype of melanocytic neoplasm and heavily influenced by the pathologists’ personal experience and training. all melanoma subtypes, including desmoplastic, spitzoid, nevoid, lentigo maligna, and superficial spreading melanoma, can mimic benign nevus variants to varying degrees. diagnoses require the integration of multiple factors including histopathologic and clinical features, variants of melanoma subtypes, patient age and anatomic location.12 difficult-todiagnose lesions are commonly sent for second opinions to expert dermatopathologists who have more experience with challenging cases; however the nature of many lesions remains ambiguous with discordant rates of lesions in this category of 25-43%.7 studies detailing the prevalence, outcome, and misdiagnosis of these lesions indicate that improved ancillary diagnostic technologies could be greatly beneficial to the dermatopathologist and dermatologist in determining the most appropriate treatment plan.8–10,13–18 efforts to improve melanoma diagnosis have traditionally focused on ancillary tests such as immunohistochemistry (ihc), fluorescence in situ hybridization (fish), and comparative genomic hybridization (cgh), but each has limitations.19–22 fish and cgh may have some limitations including less than optimal specificity and less availability than ihc. ihc is the most commonly utilized diagnostic tool for melanocytic lesions, but ihc, including ki67, melan-a/mart-1 and p16, is limited in its ability to distinguish benign from malignant melanocytic lesions.23 similarly, a recently developed prame ihc assay has exhibited staining patterns in approximately 14% of nevi, some of which are above the threshold established for a diagnosis of melanoma.24 definitive diagnosis is also complicated for a subset of lesions described as being borderline, indeterminant, of unknown malignant potential (ump), atypical melanocytic proliferation (amp) or in a ‘grey’ zone.25–33 clinical management of these cases usually results in conservative treatment for the ‘most significant consideration in the differential diagnosis’.27 gep has been employed to improve the diagnosis of these suspicious pigmented lesions. while a 2-gene pigmented lesion array (2-gene)34–39 and a 23-gene expression profile (gep) test40,41 have been previously developed, the 2-gene utility is focused on guiding biopsy decisions by dermatologists; whereas, the 23-gep labels a substantial number of lesions (~15% across studies) as indeterminate rather than introduction skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 508 providing a result of benign or malignant.40,41 approximately 10% of unequivocal cases and 15% of ambiguous lesions may be labeled indeterminate by the 23-gep test.42 although sensitivity and specificity is reported at 91.5% and 92.5%40–44, respectively, for the 23-gep, there exists an opportunity to significantly increase the accuracy and thus optimize the management of the melanoma patient, particularly given the advances in melanoma prognosis and treatment over the past decade. in this study we describe the development and validation of a 35-gep test to differentiate between benign and malignant pigmented lesions with greater accuracy than previously developed tests. a training cohort of samples, including subtypes considered challenging to diagnose, was established and bioinformatic and machinelearning approaches were used to select and prioritize genes associated with benign or malignant biology. the test was validated using an independent cohort of cases and demonstrates sensitivity and specificity metrics exceeding those currently reported in the melanoma diagnostic literature while maintaining a minimal indeterminate-risk zone. the novel 35-gep test could aid in the diagnosis of suspicious pigmented lesions and improve accuracy alone or when used in combination with currently applied diagnostic tools. sample and clinical data collection archival benign samples and associated deidentified clinical data were collected from multiple independent dermatopathology laboratories as part of this institutional review board (irb)-approved study. formalin-fixed, paraffin-embedded (ffpe) pigmented lesion tissue was collected as 5 μm sections for subsequent diagnosis based on h&e staining and for real-time quantitative reverse transcription pcr (qrtpcr) analysis. additionally, archival melanoma samples and de-identified clinical data were obtained from specimens submitted to castle biosciences for clinical testing with the 31-gep (decisiondxmelanoma). a total of 951 samples diagnosed between january 2013 and august 2020 were included in the training and validation cohorts, of which 498 were benign and 453 malignant. all laboratory personnel were blinded to clinical diagnoses for all 951 samples. samples were excluded from the study if there was less than 10% tumor volume (cellularity of all samples was determined by a single dermatopathologist), tissue originated from melanoma metastases, lesions were not primary to the skin, tissue was derived from re-excisions (including wide local excision), diagnosis was a nonmelanocytic neoplasm, or if patients had previous radiation or immunotherapy treatment. melanoma subtypes of acral lentiginous, desmoplastic, lentiginous, lentigo maligna, nevoid, nodular, spitzoid, superficial spreading, and melanoma in situ were included. benign subtypes of blue nevus, common nevus (compound, junctional and intradermal), deep penetrating nevus, dysplastic nevus (compound and junctional), and spitz nevus were included. histopathologic examination eight dermatopathologists participated in sample acquisition, and six dermatopathologists participated in sample review for diagnostic concordance. the majority of these dermatopathologists are affiliated with private practice and have an average of 12 years of experience reviewing skin lesions. all acquired samples were received with the original pathology report. methods skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 509 for all benign diagnoses, the contributing dermatopathologists provided a description of the lesion in a free text field, and the information was entered into the clinical research form. all benign samples then underwent h&e diagnostic review by a second and third dermatopathologist who were blinded to the original diagnosis and provided with only patient age and anatomic location of the lesion. reviewing dermatopathologists were asked to select a diagnosis (benign, malignant, or unknown (unknown malignant potential (ump)) as well as a subtype classification from a predetermined list. if discordance was observed across three diagnoses, the case was reviewed by additional dermatopathologists in a blinded manner for adjudication. a total of 395 samples that were diagnosed as benign by 3 out of 3 dermatopathologists were included in the study; additionally, 78 cases diagnosed as ump by no more than 1 dermatopathologist (i.e. 2 benign and 1 ump) were added to the training and validation cohorts. as a result, the final training and validation cohorts consisted of benign samples with full diagnostic concordance (167/200 and 228/273 of samples, respectively) and samples with no more than one ump classification (33/200 and 45/273, respectively). real-time quantitative reversetranscription pcr pigmented lesions were processed for qrtpcr expression analysis in a central cliacertified, cap-accredited, and new york state department of health permitted laboratory. tumor sections were macrodissected from unstained ffpe tissue and total rna was extracted per manufacturer’s instructions using either the qiasymphony sp automated nucleic acid extractor (qiagen) or kingfisher flex (thermofisher scientific) platforms. total rna concentration was quantified using the nanodrop 8000 (thermofisher scientific). cdna was obtained using the high-capacity cdna reverse transcription kit (applied biosystems). cdna pre-amplification reaction was performed utilizing the taqman preamp master mix (applied biosystems) and a 14-cycle amplification. pre-amplified samples were diluted 1:2.5x in te buffer ph 7.0 (thermofisher scientific) and combined with an equal volume of 2x open array real-time pcr master mix (applied biosystems). the samples were loaded onto a custom open array gene card using the quantstudio 12k flex accufill system (applied biosystems) subsequently run on the quantstudio 12k pcr system. expression analysis and diagnosis assignment the array data was analyzed to identify genes that were best able to segregate benign and malignant lesions based on levels of gene expression.45–47 the resulting gene set was then reviewed to ensure that a wide variety of biological pathways were represented and to confirm the biological relevance of those genes. as a result, 76 candidate diagnostic genes were selected for model training. three genes (fxr1, hnrnpl, and ykt6) were reliably and consistently expressed in the study cohort and chosen as control genes. triplicate gene expression data were aggregated and normalized using control probes. failure of three or more candidate genes (mgf, multiple gene failure) led to sample exclusion from training and validation cohorts, while control genes were evaluated independently, and failure of any control gene resulted in sample exclusion. following quality control measures to assess amplification and stability of gene expression, 58 discriminant probes and 3 control probes were selected for further analysis. deep learning techniques were applied to gene expression data for gene selection and model identification.48–50 gene expression data analyzed with neural skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 510 network modeling resulted in two diagnostic algorithms.51,52 tumors with spitzoid or melanoma in situ features had poorer initial classification accuracy; therefore, the presence of those features in diagnosis was added to the input of the algorithm to improve accuracy. algorithm improvement continued until the mean kappa value improved by less than 0.01 for the top 25% of the assay population. hyperparameter selection and model evaluation was performed using 4x4-fold cross validation.50,53 kappa was determined from the average kappa value at each of the cross validation runs. the final model was trained against all training data using the optimal gene set. two models were developed which together generated the locked algorithm for the 35-gep test. classification into benign (gene expression profile suggestive of benign neoplasm), intermediate-risk (gene expression profile cannot exclude malignancy) or malignant (gene expression profile suggestive of melanoma) zones was determined from the probability scores from both algorithms. analysis was performed with r v.3.3.3. differences in age were assessed using the wilcoxon f test. differences in categorical variables including sex, ulceration status and location were assessed by pearson chisquare test. p values <0.05 were considered statistically significant. sample cohorts quantitative rt-pcr was performed on 498 benign and 453 malignant lesions accrued under an irb-approved protocol in a multicenter cohort (figure 1). thirty-two samples (~3.4%) of the study cohort were excluded from further analysis due to mgf with the remaining 919 samples randomized to training or validation cohorts while conserving benign or melanoma subtype representation in each cohort. training (200 benign nevi and 216 melanomas) and validation (273 benign nevi and 230 melanomas) cohorts’ demographic details are shown in table 1. no statistically significant differences were observed in the training vs. validation cohorts. the median age of patients with benign lesions was 47 (range 7-85) years in the training cohort and 48 (2-90) years in the validation cohort (p=0.944), while patients with malignant tumors had a median age of 66 (range 1893) and 67 (25-98) years of age (p=0.203), respectively. training and validation cohorts had 55% and 63% (p=0.071) male patients with malignant diagnosis, while 46% and 39% (p=0.17) males were included in training and validation, respectively. ulceration was present in 29.5% (64/216) melanomas in training and 23.5% (54/230) melanomas in validation cohorts (p= 0.141). the majority of malignant lesions were biopsied from arms and legs (extremities, 40% of cases in training and validation, p=0.812), while benign lesions were mainly located on patients’ backs (36.5% in training cohort and 41% in validation, p=0.863). the distribution of different subtypes of melanoma and nevi in the training and validation sets are provided in table 2. development of 35-gep profile artificial neural networks were selected as the model type due to their ability to recognize multiple patterns, which is critical for successfully distinguishing different subtypes of benign nevi and melanomas. therefore, to represent biological diversity and different growth patterns and features, lesions unanimously diagnosed as benign by 3/3 reviewers and lesions with less definitive histopathology resulting in 2/3 concordance were included in the training set to ensure the resulting algorithm is results skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 511 figure 1. study cohorts *mgf (multiple gene failure) rules: control genes were evaluated independently and failure of any control gene resulted in sample exclusion. triplicate gene expression data were aggregated and normalized using control probes. samples with failure to amplify ≥3 out of 73 genes were excluded from model development and validation. capable of classifying both typical and heterogenous lesions. a 35-gep comprising 32 discriminant genes and 3 control genes was developed using neural networks for model fitting and genetic algorithms for feature selection on a diverse set of benign and malignant samples. the 35-gep is primarily composed of genes in cytoskeletal and barrier functions, gene regulation and melanin biosynthesis (table 3).54–78 multiple molecular pathways have been associated with melanoma progression and the 35-gep signature includes several genes from key signaling networks to encompass the complexity of the disease. biological processes such as epithelial cell differentiation, tissue and epidermis development, programmed cell death, and keratinocyte differentiation were identified as top functional enrichments for this gene set. validation of the 35-gep accuracy metrics within the validation cohort (all ages included) were 99.1% (95% ci: 97.9-100%) sensitivity, 94.3% (95% ci: 91.5-97.1%) specificity, 93.6% (95% ci: 90.5-96.7%) positive predictive value (ppv) and 99.2% (95% ci: 98.1-100%) negative predictive value (npv) (table 4), suggesting that the 35-gep test could be a highly accurate ancillary test for diagnosis of melanocytic neoplasms. in patients ≥18 years old the 35-gep had sensitivity of 99.1% (95% ci: 97.9-100%), specificity of 96.2% (95% ci: 93.8-98.6%), ppv of 96.1% (95% ci: 93.6-98.6%) and npv of 99.1% (95% ci: 97.9-100%) (table 4). accuracy metrics were calculated without the inclusion of lesions identified as intermediate-risk (3.6% and 3.8% of the total samples in all ages and ≥18 years old, respectively). overall, the 35-gep was able to accurately classify different subtypes of melanoma and nevi as benign or malignant (table 5). the 35-gep accurately classified melanoma lesions as malignant in 14/14 desmoplastic melanomas, 25/26 lentigo maligna, 15/15 nevoid, 59/60 nodular, 72/77 superficial spreading, and 17/19 melanoma in situ. furthermore, nevi were also appropriately classified as benign for 42/45 blue, 96/99 common nevi (including 15 compound, 40 intradermal and 10 junctional), 82/91 dysplastic nevi (including 44 compound and 38 junctional), and 26/36 spitz nevi. of 230 melanomas, two were identified as benign, while 15 of 273 benign lesions were classified as malignant (table 6). one of the melanomas that was classified as benign was in situ and one was nodular melanoma with a breslow thickness of 4.0 mm that had the low-risk prognostic class 1b 31-gep result. among the 15 benign lesions that were classified as malignant by the 35-gep, four were dysplastic (one compound with mild atypia and three junctional with mild/moderate atypia), one compound nevus, one combined blue and intradermal nevus, one blue nevus, one benign skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 512 table 1. demographic information for training and validation cohorts training cohort† validation cohort† melanoma n=216 benign nevi n=200 melanoma n=230 benign nevi n=273 age, median (range) 66 (18-93) 47 (7-85) 67 (25-98) 48 (2-90) sex, % male 55 46 63 39 breslow thickness, mm (range) 1.22 (0-10) na 1.23 (0.1-4.9) na t stage, % (n) t1a 29 (56) 23 (48) t1b 13 (25) 20 (42) t2a 16 (31) 16.5 (35) t2b 14 (27) 11 (23) t3a 11.5 (23) 17.5 (37) t3b 16 (31) 11 (23) t4b 0.5 (1) 1 (2) ulceration % (n) present 29.5 (64) 23.5 (54) absent 70.5 (152) 76.5 (176) not addressed 100 (200) 100 (273) location on body, % (n) abdomen/chest 8 (18) 11 (22) 5.5 (13) 11.5 (32) acral 3 (6) 1 (2) 2 (5) 1 (2) back 27 (58) 36.5 (73) 29 (67) 41 (113) extremities 40 (86) 23 (46) 40 (91) 20 (54) head/neck 20 (43) 24 (48) 22 (50) 23 (63) other 2 (5) 4.5 (9) 1.5 (4) 3.5 (9) †no statistically significant differences were observed in the training vs. validation cohorts. na – not addressed. melanocytic nevus (not otherwise specified), and seven were spitz nevi. six of the seven misclassified spitz nevi were in pediatric patients suggesting this may be a limitation of the 35-gep (accuracy metrics for the validation cohort without lesions with spitzoid features is provided in table 4). spitzoid lesions are particularly difficult to diagnose as many have ambiguous histologic characteristics and may involve regional lymph nodes in the absence of increased mortality rates or malignant potential.16,30,79 35-gep intermediate-risk zone given the potential biological transition of melanocytic lesions from a benign to a malignant state, the 35-gep profile was developed to identify lesions with an intermediate-risk of malignancy. inclusion of a wide variety of subtypes in the study improved the classification of lesions as benign or malignant and led to a limited intermediate-risk zone. a total of 96.4% of cases had a definitive benign or malignant test result and only 3.6% (18/503) of cases were classified as intermediate-risk, including eight melanomas and ten benign nevi. though a definitive benign or malignant result is advantageous for implementing patient management pathways, samples with probability scores in the intermediate-risk zone may be evolving, borderline, or atypical and warrant special consideration in terms of patient management with a focus on clinicopathologic correlation. dermatopathologists have a number of ancillary tools available to assist with the discussion skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 513 diagnosis of pigmented lesions, yet there is a substantial amount of diagnostic discordance that may potentially lead to overtreatment of patients with benign lesions and undertreatment of patients with melanoma.80 the 35-gep test to distinguish benign from malignant pigmented lesions was developed to improve diagnostic accuracy and reduce diagnostic uncertainty for difficult-to-diagnose cases. table 2. distribution of subtypes in training and validation cohorts training cohort, n validation cohort, n p value melanoma 216 230 0.399 acral lentiginous 6 5 desmoplastic 15 14 lentiginous 3 3 lentigo maligna 23 26 in situ 21 19 nevoid 15 15 nodular 47 60 superficial spreading 66 77 spitzoid 15 3 not specified 5 8 nevi 200 273 0.468 blue 38 45 common nevi compound 16 16 intradermal 20 41 junctional 10 10 not specified 30 32 deep penetrating 1 2 dysplastic compound 40a 49b junctional 28c 42d spitz 17 36 p value was calculated using the pearson chi-square test. dysplastic nevi had different degrees of atypia: a mild (n=19), moderate (n=4) and severe (n=3); b mild (n=24), moderate (n=2), and severe (n=3); c mild (n=20) and moderate (n=6); d mild (n=22) and moderate (n=17) atypia. table 3. genes included in the 35-gep and their functions gene classification gene symbol gene name barrier function hal histidine ammonia-lyase barrier function mgp* matrix gla protein barrier function cst6* cystatin-m barrier function gja1* gap junction alpha-1 protein barrier function csta cystatin a barrier function clca2* calcium-activated chloride channel regulator 2 cytoskeleton involved krt17 keratin, type i cytoskeletal 17 cytoskeleton involved ppl* periplakin cytoskeleton involved krt2 keratin 2 cytoskeleton involved ablim1 actin binding lim protein 1 cytoskeleton involved dsp desmoplakin cytoskeleton involved nes nestin gene regulation klf5 kruppel-like factor 5 gene regulation gata3 gata binding protein 3 gene regulation bap1* ubiquitin carboxylterminal hydrolase bap1 gene regulation tp63 tumor protein p63 gene regulation sap130* histone deacetylase complex subunit sap130 gene regulation sfn 14-3-3 protein sigma melanin biosynthesis gpr143 g-protein coupled receptor 143 melanin biosynthesis wipi1 wd repeat domain phosphoinositideinteracting protein melanin biosynthesis dct dopachrome tautomerase melanin biosynthesis atp6v0e2 atpase h+ transporting v0 subunit e2 skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 514 melanin biosynthesis ptn pleiotrophin protein synthesis rps16 40s ribosomal protein s16 protein synthesis rpl37a 60s ribosomal protein l37a tumorigenesis bcl2a1 bcl-2-related protein a1 tumorigenesis btg1* protein btg1 tumorigenesis anxa8l1 annexin a8-like protein 1 tumorigenesis dusp4 dual specificity protein phosphatase 4 tumorigenesis cxcl14* c-x-c motif chemokine 14 tumorigenesis s100a8* protein s100-a8 tumorigenesis s100a9* protein s100-a9 housekeeping fxr1* rna binding protein housekeeping hnrnpl* mrna function protein housekeeping ykt6* er membrane protein * fourteen genes are also included in the 31-gep test. a cross-study analysis shows that in an independent validation cohort of 503 benign lesions and melanomas the 35-gep test demonstrated improved accuracy compared to other diagnostic tools based on their primary validation studies (table 7). unlike fish, cgh or ihc, gene expression profiling captures transcriptomic events within the lesion and the surrounding tissue, allowing for a more comprehensive assessment of the biological changes that are associated with the transition to a malignant phenotype.22,81,82 ihc generally allows for evaluation of changes in the expression of a single biomarker at the protein level, which can be limited by subjective quantification systems.83 prame ihc has been reported as a reliable method to distinguish benign from malignant pigmented lesions; however, ~14% of nevi can have some staining for prame and the interpretation of positive staining (4+, ≥76% of immunoreactive tumor cells are prame positive) can be subjective. thus, prame ihc requires further validation for widespread clinical use due to the potential for misdiagnosis of benign lesions as malignant.24,84 in the current study, prame expression did not improve diagnostic accuracy above the results reported for the 35-gep (data not shown). in this study, the 35-gep reliably diagnosed 96.4% of benign and malignant lesions. in cross-study comparison (table 7), the 35test out-performed a 23-gep diagnostic test with previously reported accuracy metrics for unequivocal samples ranging from 91.5-94% for sensitivity, 90.0-92.5% for specificity, and technical failures in 14.7%. moreover, ~15% of diagnostically concordant (i.e. 3 out of 3) cases could not be classified as benign or malignant.40,41 by comparison, the 35-gep test demonstrated sensitivity (99.1%) and specificity (94.3%) in all ages and 99.1% sensitivity and 96.2% specificity in patients ≥18 years old, a low number of technical failures (3.4%), and no more than 3.8% of cases received an intermediate-risk result. the improved classification of lesions compared to that of the 23-gep test is likely due to implementation of highly sophisticated modeling (neural networks) that resulted in two algorithms with 32 diagnostic and 3 control genes, the inclusion of samples with different growth patterns (total of nine melanoma subtypes and eight benign subtypes) in the training cohort as well as incorporation of lesions with 2/3 concordance. data supporting the utility of the 23-gep test in ambiguous or diagnostically discordant lesions is limited.44 recently, sensitivity of 90.4% and specificity of 95.5% was reported for 125 ‘uncertain’ cases, however, the definition of uncertainty was broad and included lesions as discordant if a differing skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 515 table 4. the 35-gep accuracy metrics all ages n=503 >18 years old n=478 all ages* n=464 ≥18 years old* n=457 35-gep 95% ci 35-gep 95% ci 35-gep 95% ci 35-gep 95% ci sensitivity 99.1% 97.9-100 99.1% 97.9-100 99.1% 97.8-100 99.1% 97.8-100 specificity 94.3% 91.5-97.1 96.2% 93.8-98.6 96.5% 94.2-98.9 96.4% 94.0-98.9 ppv 93.6% 90.5-96.7 96.1% 93.6-98.6 96.5% 94.1-98.9 96.5% 94.1-98.9 npv 99.2% 98.1-100 99.1% 97.9-100 99.1% 97.9-100 99.1% 97.8-100 intermediate-risk result 3.6% 3.8% 3.0% 3.1% samples that fall in intermediate-risk zone were excluded from the calculation. *lesions with spitzoid features were excluded. ppv – positive predictive value; npv – negative predictive value; ci – confidence interval. diagnosis was received from just 1 of 7 dermatopathologists reviewing the cases.85 in this study, we included cases with concordance for 2 of 3 reviewing dermatopathologists in this independent 35gep validation. the 35-gep was developed and validated using fully concordant lesions and a small set of ‘borderline’ cases, where no more than 1 out of 3 dermatopathologists indicated ‘unknown malignant potential’ as a diagnosis. since the 35-gep will be most likely used in difficult-to-diagnose lesions, inclusion of 2/3 concordant cases to capture differentially expressed genes from those histopathologically challenging cases was factored into the neural network configuration during the test development. with the improved accuracy metrics and substantially reduced intermediate-risk zone, dermatopathologists can expect a definitive result from the 35-gep test in ≥95% of lesions submitted for testing. it is our hope that improved test characteristics for the disambiguation of pigmented lesions will help refine guidelines for when to utilize gep in the diagnosis of challenging pigmented lesions. although the vast majority of cases tested by the 35-gep will have a definitive score of benign or malignant risk potential, 3.6% of cases fell into an intermediate-risk zone reflective of a molecular biology characteristic of both benign and malignant lesions. though the prevalence is not known, evidence that there is a true ‘transition’ zone for pigmented lesions is mounting.46 thus, interpretation of an intermediate-risk result of the 35-gep should be considered in the context of other clinicopathological information. specifically, in cases with an intermediate-risk score, it would be of great diagnostic importance to exclude the possibility of sampling error and ensure that the entire clinical lesion has been evaluated by routine histopathology. unfortunately, up to 1/3 of nevi transition to melanoma, so there is a subset of lesions that may be clinically identified during this progression.12,86 in addition, there are atypical melanocytic proliferations (amps) that never evolve to full malignancy despite metastasis to regional lymph nodes. the spectrum of outcomes for these lesions warrants special consideration in clinical management.28 clinical management of amps varies as there are no official guidelines governing their treatment, but common practice is definitive surgical treatment with removal of lesion with the margin of normal skin.28 in addition, the use of the 35-gep can provide the dermatologist and/or patient with treatment options to cover the most severe of diagnoses, including a diagnosis of melanoma. studies are underway in a true amp population with skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 516 table 5. performance of the 35-gep in different subtypes of nevi and melanoma 35-gep result benign, n intermediaterisk, n malignant, n melanomas 2 8 220 acral lentiginous 5 desmoplastic 14 lentiginous 3 lentigo maligna 1 25 in situ 1 1 17 nevoid 15 nodular 1 59 spitzoid 1 2 superficial spreading 5 72 not specified 8 nevi 248 10 15 blue 42 2 1 common nevi compound 15 1 intradermal 40 1 junctional 10 not specified 31 1 deep penetrating nevus 2 dysplastic compound 44a 4b 1c junctional 38d 1e 3f spitz 26 3 7 dysplastic nevi had different degrees of atypia: a – mild (n=22), moderate (n=2) and severe (n=3); b – mild (n=1); c mild (n=1); d mild (n=21) and moderate (n=14); e – moderate (n=1); f – mild (n=1) and moderate (n=2) atypia. known outcomes. the 35-gep test performed equally well in nevi and melanomas with different growth patterns. for instance, classification of lentigo maligna, nodular and superficial spreading melanomas was concordant with dermatopathologic diagnosis as were blue and common nevi (compound, intradermal and junctional), along with dysplastic nevi with varying degree of atypia with only a small percentage receiving an intermediaterisk result. further studies to increase the number of samples in subtypes that were not represented in large enough numbers are underway. accuracy metrics of the 35gep with and without spitzoid lesions and pediatric participants are presented in table 4. the spitz subtype is particularly challenging and thus far all available ancillary tests have had limitations in sensitivity and specificity.42,87,88 of note, absence of spitzoid melanomas and classification of the spitz lesions in pediatric patients was not optimal in this study and therefore further studies are being undertaken to confirm whether this is a limitation of the 35-gep. for the dermatologist, metastatic risk assessment is critical for guiding appropriate patient management following a melanoma diagnosis. a prognostic 31-gep test has been validated to determine individualized 5year risk for recurrence, metastasis and melanoma-specific survival.89–91 based on accuracy metrics and multivariate models demonstrating that the test is an independent and significant risk-prediction tool, the value of the gep testing as an adjunct to current staging factors has been recognized by the national comprehensive cancer network.92 thus, patients diagnosed with malignant lesions have effective prognostic tools and contemporary therapies, with demonstrated improved outcomes, at their disposal. given the availability of the prognostic 31gep test for cutaneous melanoma, the 35gep test was developed to refine the diagnosis of benign nevi and melanomas by providing dermatopathologists with an objective ancillary tool to aid in their diagnosis of difficult-to-diagnose pigmented conclusion skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 517 table 6. seventeen cases (3.4% of the independent validation cohort) were misclassified by the 35-gep sample number 35-gep result sex age growth pattern submitted by dermatopathologist atypia breslow thickness, mm ulceration location 91 malignant male 2 spitz nevus none na na extremities 315 malignant male 3 spitz nevus, compound none na na extremities 95 malignant male 6 spitz nevus none na na head/neck 98 malignant male 6 spitz nevus none na na head/neck 129 malignant male 8 benign pigmented spindle-cell nevus of reed (variant of spitz) none na na extremities 318 malignant male 8 pigmented spindle cell variant of spitz's nevus none na na head/neck 297 malignant male 33 junctional melanocytic nevus mild na na back 266 malignant female 36 junctional spitz nevus none na na extremities 300 malignant male 37 compound dysplastic melanocytic nevus mild na na back 69 malignant female 42 combined blue and intradermal nevus none na na abdomen/chest 46 malignant female 43 junctional dysplastic nevus moderate na na back 138 malignant female 55 benign melanocytic nevus none na na acral 324 malignant female 56 compound melanocytic nevus none na na back 323 malignant female 58 intradermal melanocytic nevus none na na extremities 313 malignant male 61 junctional melanocytic nevus moderate na na back 566 benign female 63 melanoma in situ na na no extremities 404 benign male 83 nodular melanoma na 4.0 no head/neck na – not addressed. lesions. clinically implemented gep tests for diagnostically challenging melanocytic lesions have demonstrated high impact on utility for guiding decision-making.93,94 although not the focus of this study, assessment of 35-gep clinical utility, as well as correlation of test results with outcomes, is underway. in the zone of significant uncertainty, the high accuracy metrics of the test might increase confidence level in diagnosis to dermatopathologists and dermatologists, while providing assurance to the patients. the test also provided a definitive result for 96.4% of the lesions in the validation study, offering an opportunity to reduce the uncertainty associated with pigmented lesions and promote more definitive management of patients by dermatologists. an ancillary test with the characteristics reported here could impact expenditure on over-diagnoses by decreasing unnecessary surgeries, imaging and follow-up while more appropriately allocating healthcare resources to those lesions where malignant risk is identified. skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 518 table 7. comparison of 35-gep to currently available ancillary tests study number of cases type of test sensitivity specificity technical failure nevi subtypes included melanoma subtypes included current study 503 35-gep 99.1% 94.3% 3.4% blue, common, deep penetrating, dysplastic, spitz acral, desmoplastic, lentiginous, lentigo maligna, in situ, nevoid, nodular, superficial spreading, spitzoid clarke et al.41 437 23-gep 94.0% 90.0% 14.7% blue, common, dysplastic, spitz acral, lentigo maligna, nodular, superficial spreading clarke et al.40 736 23-gep 91.5% 92.5% na not reported acral, lentigo maligna, nodular, superficial spreading gerami et al.92 196 fish# 86.7% 95.4% na acral, blue, common, dysplastic, spitz not reported gerami et al.93 233 fish# 83.0% 94.0% na blue, common, dysplastic, spitz acral, lentigo maligna, nodular, superficial spreading lezcano et al.24 400 prame ihc 84.7%& 99.2%& na common, dysplastic, spitz acral, cutaneous paramucosal, desmoplastic, lentigo maligna, nevoid, nodular, superficial spreading lezcano et al.87 110 prame ihc 75.0% 98.8% na blue, common, deep penetrating, dysplastic, spitz acral, malignant melanoma, nevoid, spitzoid # 6p25, cep 6, 6q23, and 11q13 & calculated from the data reported in the manuscript. na – not addressed. conflict of interest disclosures: sie is a consultant and shareholder of castle biosciences, inc. asf, cjc, pg are consultants for castle biosciences, inc. oz, bhr, jw, lms, ldb, and krc are employees and shareholders of castle biosciences, inc. msg is an employee of castle biosciences, inc. funding: this study was sponsored by castle biosciences, inc. corresponding author: sarah i. estrada, md 20401 n 73rd st., #230 scottsdale, az 85255 phone: 480-563-7507 fax: 480-563-7508 email: sestrada@affderm.com references: 1. national cancer institute, national institutes of health. melanoma of the skin cancer stat facts. seer. published 2020. accessed october 24, 2019. https://seer.cancer.gov/statfacts/html/melan.html 2. wang dm, morgan fc, besaw rj, schmults cd. an ecological study of skin biopsies and skin cancer treatment procedures in the united states medicare population, 2000 to 2015. j am acad dermatol. 2018;78(1):47-53. doi:10.1016/j.jaad.2017.09.031 3. cartee tv, kini sp, chen sc. melanoma reporting to central cancer registries by us dermatologists: an analysis 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c, covington kr, leachman s. clinical utility of a 31gene expression profile test to determine eligibility for sentinel lymph node biopsy in melanoma patients >65 years of age. in: ; 2018. 92. swetter sm, thompson ja, coit dg, et al. nccn clinical practice guidelines in oncology. cutaneous melanoma. version 3.2020. published online may 18, 2020. 93. cockerell c, tschen j, billings sd, et al. the influence of a gene-expression signature on the treatment of diagnostically challenging melanocytic lesions. pers med. 2017;14(2):123-130. doi:10.2217/pme-2016-0097 94. cockerell cj, tschen j, evans b, et al. the influence of a gene expression signature on the diagnosis and recommended treatment of melanocytic tumors by dermatopathologists: medicine (baltimore). 2016;95(40):e4887. doi:10.1097/md.0000000000004887 summary and conclusion • cemiplimab is the first systemic therapy to show clinical benefit in patients with labcc after hhi therapy with a 31.0% orr per icr. among responders, the estimated 12-month dor was 85.2%. • the safety profile is considered acceptable for the patient population. it is generally consistent with other pd-1 antibodies and with previous reports of cemiplimab in other tumor types. • baseline pd-l1 expression is not associated with clinical activity. • these results provide strong rationale for cemiplimab as a treatment option for patients with labcc in the second-line (or greater) setting. synopsis • hedgehog inhibitors (hhis), such as vismodegib and sonidegib, are approved for the treatment of patients with metastatic basal cell carcinoma (bcc) or locally advanced bcc (labcc) who are not candidates for surgery or radiation.1,2 • however, for patients with labcc, there is no approved treatment after first-line hhi therapy.3 • cemiplimab is a high-affinity, highly potent, human programmed cell death (pd)-1 antibody, which has demonstrated anti-tumor activity in advanced solid tumors.4–6 • cemiplimab is an established therapy approved for treatment of advanced cutaneous squamous cell carcinoma (cscc) in patients who are not candidates for curative surgery or curative radiation.7 • both bcc and cscc are keratinocytic tumors with high mutational burden due to ultraviolet mutagenesis and are potentially amenable to immunotherapy.3,8 • we present the primary analysis of the labcc cohort from the pivotal phase 2 study of cemiplimab in the second-line (or greater) setting (nct03132636). primary analysis of phase 2 results for cemiplimab in patients (pts) with locally advanced basal cell carcinoma (labcc) who progress on or are intolerant to hedgehog inhibitors (hhis) alexander j. stratigos,1 aleksandar sekulic,2 ketty peris,3 oliver bechter,4 martin kaatz,5 karl d. lewis,6 nicole basset-seguin,7 anne lynn s. chang,8 stéphane dalle,9 almudena fernandez orland,10 lisa licitra,11 caroline robert,12 claas ulrich,13 axel hauschild,14 michael r. migden,15 reinhard dummer,16 siyu li,17 kosalai mohan,18 ebony coates,18 vladimir jankovic,18 nathalie fiaschi,18 emmanuel okoye,18 ioannis bassukas,19 carmen loquai,20 vincenzo de giorgi,21 zeynep eroglu,22 ralf gutzmer,23 jens ulrich,24 susana puig,25 frank seebach,18 gavin thurston,18 israel lowy,18 timothy bowler,18 matthew g. fury18 1andreas sygros hospital-university of athens, athens, greece; 2arizona mayo clinic, phoenix, az, usa; 3catholic university of the sacred heart and fondazione policlinico universitario a. gemelli-irccs, rome, italy; 4department of general medical oncology, university hospitals, leuven, belgium; 5srh wald-klinikum gera gmbh, gera, germany; 6university of colorado hospital, aurora, co, usa; 7hopital saint-louis, paris, france; 8department of dermatology, stanford university school of medicine, stanford, ca, usa; 9department of dermatology, hcl cancer institute, lyon cancer research center, lyon, france; 10hospital universitario virgen macarena, seville, spain; 11fondazione irccs istituto nazionale dei tumori and university of milan, milan, italy; 12dermatology unit, gustave roussy cancer center and paris-saclay university, villejuif, france; 13charite-universitiitsmedizin berlin, berlin, germany; 14department of dermatology, university of kiel, kiel, germany; 15the university of texas md anderson cancer center, houston, tx, usa; 16university hospital zurich, zurich, switzerland; 17regeneron pharmaceuticals, inc., basking ridge, nj, usa; 18regeneron pharmaceuticals, inc., tarrytown, ny, usa; 19university of ioánnina, ioánnina, greece; 20department of dermatology, university medical center mainz, germany; 21university of florence, florence, italy; 22department of cutaneous oncology, moffitt cancer center, tampa, fl, usa; 23skin cancer center hannover, department of dermatology and allergy, hannover medical school, hannover, germany; 24skin cancer center, department of dermatology, harz clinics, quedlinburg, germany; 25hospital clínic & universitat de barcelona and centro de investigación biomédica en red de enfermedades raras (ciberer), instituto de salud carlos iii, barcelona, spain table 1. patients demographics and baseline characteristics labcc (n=84) median age, years (range) 70.0 (42–89) gender, % (n) male 66.7 (56) female 33.3 (28) ecog performance status, %, (n) 0 60.7 (51) 1 39.3 (33) primary site of tumor, % (n) head and neck 89.3 (75) extremity 2.4 (2) trunk 8.3 (7) reason for discontinuation of prior hhi, % (n)* progression of disease on hhi 71.4 (60) intolerant to prior hhi therapy 38.1 (32) intolerant to vismodegib 38.1 (32) intolerant to sonidegib 4.8 (4) no better than stable disease after 9 months on hhi therapy 8.3 (7) *sum is >84 because some patients had more than one reason for discontinuation. table 2. evaluation of response n (%), unless otherwise stated labcc (n=84) objective response rate, % (95% ci) 31.0 (21.3−42.0)* complete response 5 (6.0) partial response 21 (25.0) stable disease 41 (48.8) progressive disease 9 (10.7) not evaluableϯ 8 (9.5) *includes two patients whose partial responses were confirmed after the data cut-off date. ϯof the eight patients who were not evaluable, four did not have any post-baseline tumor assessments, three patients were not considered to have evaluable lesions by either photographic or radiologic assessment methods and one patient had a second target lesion not imaged after baseline. table 4. teaes regardless of attribution n (%) labcc (n=84) any grade grade ≥3 any 82 (98) 43 (51) serious 29 (35) 22 (26) led to discontinuation 14 (17) 7 (8) associated with an outcome of death* 3 (4) 3 (4) occurred in ≥10% patients (any grade) or grade 3 in ≥5% patients fatigue 25 (30) 3 (4) diarrhea 20 (24) 0 pruritus 18 (21) 0 asthenia 17 (20) 1 (1) anemia 13 (16) 1 (1) decreased appetite 13 (16) 1 (1) headache 12 (14) 1 (1) nausea 12 (14) 1 (1) urinary tract infection 12 (14) 3 (4) arthralgia 11 (13) 0 dyspnea 10 (12) 0 blood creatinine increased 8 (10) 0 dizziness 8 (10) 0 cough 8 (10) 0 hypothyroidism 8 (10) 0 tumor hemorrhage 8 (10) 0 hypertension 7 (8) 4 (5) *not considered treatment-related. teae, treatment-emergent adverse event. table 3. best objective tumor response rate by positive pd-l1 per icr n (%), unless otherwise stated evaluable pd-l1 (n=50) no evaluable pd-l1 (n=34) pd-l1 <1% (n=35) pd-l1 ≥1% (n=15) (n=34) objective response rate, % (95% ci) 26 (13−43) 27 (8−55) 38 (22−56) complete response 2 (6) 2 (13) 1 (3) partial response 7 (20) 2 (13) 12 (35) stable disease 18 (51) 9 (60) 14 (41) progressive disease 5 (14) 1 (7) 3 (9) not evaluable 3 (9) 1 (7) 4 (12) disease control rate, % (95% ci)* 77 (60−90) 87 (60−98) 79 (62−91) durable disease control rate, % (95% ci)ϯ 51 (34−69) 53 (27−79) 71 (53−85) *defined as the proportion of patients with complete response, partial response, stable disease, or non-partial response/ non-progressive disease at the first evaluable tumor assessment, scheduled to occur at week 9 (defined as 56 days to account for visit windows in the protocol). ϯdefined as the proportion of patients with complete response, partial response, stable disease, or non-partial response/non-progressive disease for at least 27 weeks without progressive disease (defined as 182 days to account for visit windows in the protocol). references 1. sun pharmaceuticals industries, inc. odomzo® (sonidegib) prescribing information. available from: https://www.accessdata. fda.gov/drugsatfda_docs/label/2017/205266s004lbl.pdf. revised september 2017. accessed october 12, 2020. 2. genentech, inc. erivedgetm (vismodegib) prescribing information. available from: https://www.accessdata.fda.gov/drugsatfda_docs/ label/2012/203388lbl.pdf. revised january 2012. accessed october 12, 2020. 3. goodman am et al. oncoimmunology 2018;7:e1404217. 4. burova e et al. mol cancer ther. 2017;16:861–870. 5. migden mr et al. n engl j med. 2018;379:341–351. 6. rischin d et al. j immunother cancer. 2020;8:e000775. 7. regeneron pharmaceuticals, inc. libtayo® [cemiplimab-rwlc] injection full us prescribing information. available from: https://www.accessdata.fda.gov/drugsatfda_docs/ label/2018/761097s000lbl.pdf. accessed july 13, 2020. 8. inman gj et al. nat commun. 2018;9:3667. acknowledgments the authors would like to thank the patients, their families, investigators, and all investigational site members involved in this study. the study was funded by regeneron pharmaceuticals, inc. and sanofi. editorial writing support was provided by jenna lee of prime, knutsford, uk, funded by regeneron pharmaceuticals, inc. and sanofi. disclosures alexander j. stratigos reports advisory board or steering committee roles with janssen cilag, regeneron pharmaceuticals, inc., roche, and sanofi, and research support from abbvie, bms, genesis pharma, and novartis. aleksandar sekulic reports advisory roles with regeneron pharmaceuticals, inc. and roche. ketty peris reports advisory board roles with abbvie, leo pharma, janssen, almirall, lilly, galderma, novartis, pierre fabre, sun pharma, and sanofi outside the submitted work. oliver bechter has advisory board roles with novartis, bms, merck sharp & dhome, pierre fabre, and ultimovacs. martin kaatz, almudena fernandez orland, ioannis bassukas, and vincenzo de giorgi declare no conflict of interest. karl d. lewis reports grants from the university of colorado and grants and personal fees from regeneron pharmaceuticals, inc. nicole basset-seguin reports honoraria from galderma, leo, pierre fabre, novartis, and roche, consulting fees from galderma, leo, pierre fabre, novartis, roche, and sun pharmaceuticals, inc. patents, royalties, or other intellectual property from genentech/f. hoffmann-la roche, ltd., and travel, accommodations, or expenses from galderma, leo, and roche. anne lynn s. chang reports advisory roles with regeneron pharmaceuticals, inc. and merck, and research funding from regeneron pharmaceuticals, inc., merck, novartis, and galderma. stéphane dalle reports that their spouse is an employee of sanofi. lisa licitra reports institutional grants and personal fees from astrazeneca, bms, boehringer ingelheim, debiopharm international sa, eisai, novartis, and roche, institutional grants from celgene international, exelixis inc, hoffmann-la roche ltd, irx therapeutics inc., medpace inc., merck-serono, and pfizer, and personal fees from sobi, ipsen, incyte biosciences italy srl, doxa pharma, amgen, nanobiotics sa, gsk, accmed, medical science fundation g. lorenzini, associazione sinapsi, think 2 it, aiom servizi, prime oncology, wma congress education, fasi, dueci promotion srl, mi&t, net congress & education, prma consulting, kura oncology, health & life srl, and immuno-oncology hub. caroline robert reports grants and personal fees advisory board roles with bristol-myers squibb, pierre fabre, novartis, amgen, merck, roche, merck sharp & dhome, sanofi, biothera, and ultimovacs. claas ulrich reports advisory board and speaker roles for roche, sanofi, regeneron pharmaceuticals, inc., and sun pharma. axel hauschild reports institutional funding and personal fees from amgen, bms, merckserono, merck sharp & dhome/merck, philogen, pierre fabre, provectus, regeneron pharmaceuticals, inc., roche, sanofi-genzyme, novartis, and consultancy fees from oncosec, almirall hermal, and sun pharma. michael r. migden reports advisory roles with and travel fees from regeneron pharmaceuticals, inc. and sun pharmaceuticals, advisory role with rakuten medical, and research funding from regeneron pharmaceuticals, inc. and pelle pharm. reinhard dummer reports consultant or advisory roles with novartis, merck sharp & dhome, bms, roche, amgen, takeda, pierre fabre, sun pharma, sanofi, catalym, second genome, regeneron pharmaceuticals, inc., and alligator outside the submitted work. siyu li, kosalai mohan, ebony coates, vladimir jankovic, nathalie fiaschi, emmanuel okoye, frank seebach, gavin thurston, and timothy bowler are employees and shareholders of regeneron pharmaceuticals, inc. carmen loquai reports personal fees from roche, sun pharma, bms, msd, merck, novartis, pierre fabre, kyowa kirin, almiral hermal, and biontech. zeynep eroglu reports advisory board fees from regeneron pharmaceuticals, inc., novartis, array, genentech, and sunpharma, and grant from novartis. ralf gutzmer reports documentation fees to institution from regeneron pharmaceuticals, inc.; personal fees and non-financial support from amgen, bms, roche pharma, merck serono, pierre fabre, sanofi, and regeneron pharmaceuticals, inc.; grants, personal fees and non-financial support from novartis; grants and personal fees from pfizer; grants from johnson & johnson; and personal fees from merck sharp dohme, almirall hermal, sun pharma, 4sc, and bayer. jens ulrich reports grants and personal fees from sanofi, bms, novartis, and msd; personal fees from roche, medac, and sun pharma. susana puig reports personal fees and non-financial support from sanofi; other (clinical trials) from regeneron pharmaceuticals, inc.; grants from avene; non-financial support from abbie; grants, personal fees and non-financial support from isdin, la roche-posay, and roche; grants and personal fees from sun pharma; non-financial support from lilly and msd; personal fees, non-financial support and other from pfizer; grants, personal fees and other from leo pharma and almirall; personal fees and other from ojer pharma; personal fees from pierre fabre; non-financial support from mavig, fotofinder, and 3gen; personal fees, non-financial support and other from novartis, grants and personal fees from amgen. israel lowy and matthew g. fury are employees of, have patents pending, and are shareholders of regeneron pharmaceuticals, inc. 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 0 2 4 6 8 10 12 14 16 18 20 22 24 26 month 84 76 64 56 48 40 35 27 15 15 9 6 2 0no. at risk p ro b a b ili ty o f p f s p ro b a b ili ty o f o s 28 0 estimated median pfs, months: 19.3 (95% ci: 8.6–ne) estimated 12-month event-free probability: 56.5% (95% ci: 44.3–67.0) estimated median os, months: not reached (95% ci: ne–ne) estimated 12-month probability of survival: 92.3% (95% ci: 83.6–96.5) 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 month 84 83 80 78 73 72 66 61 51 35 25 15 3 0 0no. at risk figure 4. pfs and os in responding patients group 1 − adult patients with metastatic (nodal and distant) bcc group 2 − adult patients with labcc 350 mg cemiplimab iv q3w for up to 93 weeks tumor assessments 1–5 q9w, 6–9 q12w tumor response assessment by icr (recist 1.1 and/or modified who criteria) figure 1. study design q9w, every 9 weeks; q12w, every 12 weeks; recist 1.1, response evaluation criteria in solid tumors version 1.1; who, world health organization. presented at the 2021 winter clinical dermatology conference, january 16–24, virtual conference (encore of esmo 2020 late-breaking mini oral presentation). results patient demographics and baseline characteristics • as of february 17, 2020, 84 patients were enrolled; 66.7% were male; median age was 70 years (range: 42−89) (table 1). • the most common primary site of tumor location was head and neck (89.3%) (table 1). • reasons for discontinuation of prior hhi therapy were progression of disease on hhi (71.4%), intolerant to prior hhi therapy (38.1%), and no better than stable disease after 9 months of hhi therapy (8.3%) (table 1). • median follow-up was 15 months (range: 0.5−25). objectives • the primary objective was to evaluate objective response rate (orr) by independent central review (icr). • key secondary endpoints: duration of response (dor), progression-free survival (pfs), overall survival (os), complete response by icr, and safety and tolerability. orr included two responses confirmed after the data cut-off date of february 17, 2020. methods • in this pivotal phase 2 study, patients with labcc received cemiplimab 350 mg every 3 weeks (q3w) intravenously (iv) (for up to 93 weeks or until progression, unacceptable toxicity, withdrawal of consent, or confirmed complete response) (figure 1). tumor response • orr per icr was 31.0% (95% confidence interval [ci]: 21.3−42.0), including five complete responses and 21 partial responses (table 2). this includes two responses that emerged at the last tumor assessment prior to the data cut and were confirmed by icr of tumor assessments after the date cut. tumor response by pd-l1 levels • baseline tumor samples were evaluable for pd-l1 in 50 of 84 patients (table 3). • orr was 26% (95% ci: 13−43) in 35 patients with pd-l1 less than 1% and 27% (95% ci: 8−55) in 15 patients with pd-l1 ≥1% (table 3). • there was no evaluable pd-l1 in 34 patients (table 3). • objective responses were observed in patients regardless of baseline pd-l1 levels (table 3). • immune-related adverse events (iraes, per sponsor identification method) occurred in 21 (25%) patients and were grade 3 in eight (10%) patients. no grade 4 or grade 5 iraes occurred. • the most common iraes (any grade) were hypothyroidism and colitis, in eight (10%) and five (6%) patients, respectively. • grade 3 iraes in >1 patient were colitis (n=3) and adrenal insufficiency (n=2). • adverse events of grade 3 or greater, regardless of attribution, occurred in 51% of patients (table 4). • seventeen percent of patients discontinued treatment due to teaes (table 4). • there were no treatment-related deaths (table 4). • the overall safety profile is consistent with previously reported experience with cemiplimab. • the estimated kaplan–meier probability of dor was 90.9% (95% ci: 68.3−97.6) and 85.2% (95% ci: 60.5−95.0) at 6 and 12 months, respectively. • time to response and durability of responses were observed (figure 2). • reductions of externally visible bcc lesions during cemiplimab treatment have been observed (figure 3). • median estimated pfs for all patients was 19.3 months (95% ci: 8.6−not evaluable [ne] (figure 4). • median os had not been reached at the time of data cut-off. • the estimated 12-month probability of survival was 92.3% (95% ci: 83.6−96.5) (figure 4). safety • the most common treatment-related adverse events (traes), by preferred terms, included fatigue (n=21; 25%), pruritus (n=12; 14%), and asthenia (n=12; 14%). • the most common grade ≥3 traes were colitis (n=4), fatigue, and adrenal insufficiency (n=2 each). • key inclusion criteria: histologically confirmed diagnosis of invasive bcc prior progression or intolerance to hhi therapy or no better than stable disease after 9 months on hhi therapy at least one measurable baseline lesion eastern cooperative oncology group (ecog) performance status of 0 or 1. • key exclusion criteria: ongoing or recent (within 5 years) autoimmune disease requiring systemic immunosuppression prior anti–pd-1 or anti–pd-ligand (l)1 therapy concurrent malignancy other than bcc and/or history of malignancy other than bcc within 3 years of date of first planned dose of cemiplimab, except for tumors with negligible risk of metastasis or death. a baseline post-treatment follow-up b baseline post-treatment follow-up figure 3. reductions of visible bcc lesions while on cemiplimab treatment panel a shows evidence of response from baseline (study day –24) to post-treatment follow-up (study day 726) in a 79-year-old man with progression of disease on prior vismodegib. panel b shows response from baseline (study day –17) to post-treatment follow-up (study day 708) in a 66-year-old man who had received prior radiotherapy and prior vismodegib. 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 p a ti e n ts w it h r e s p o n s e ( n = 2 6 ) month complete response partial response stable disease progressive disease not evaluable ongoing treatment ongoing study figure 2. dor in responding patients an interactive version of this poster is available here: http://www.bccinteractiveposter.com skin december 2018 volume 2 supplemental issue copyright 2018 the national society for cutaneous medicine 114 rising derm stars inhibition of isoprenoid synthesis synergizes with mapk blockade to prevent growth in targeted therapy-resistant melanoma nicholas theodosakis1, casey g. langdon1, goran micevic1, irina krykbaeva1, robert e. means1, david f. stern1, marcus w. bosenberg1,2 1department of pathology, yale school of medicine, new haven, ct 2department of dermatology, yale school of medicine, new haven, ct though targeted therapy for late-stage braf-mutant melanoma patients often produces dramatic initial results, virtually 100% of responders eventually develop drugresistant disease, usually within 6-11 months (chapman et al., 2011; sosman et al., 2012). as a result, the search for new adjunctive agents continues to be of marked clinical significance. agents previously approved and broadly-prescribed for other indications are especially attractive given their ease of utilization. hmg-coa reductase inhibitors, or statins, have previously been postulated to have anti-cancer properties. nevertheless, significant concern over their toxicity at required doses has limited their evaluation in the past. deregulation of the mevalonate pathway, upstream of cholesterol synthesis, has been noted to be important for growth in cancers such as prostate, breast, acute myeloid leukemia, and melanoma(kang et al., 2015; santos and schulze, 2012). much of this is thought to be due to the aberrantly increased production of farnesyl and geranylgeranyl groups: two types of post-translational isoprenoid moieties that affect the ability of proteins to localize to lipid rich regions such as the interior plasma membrane and the golgi apparatus. in our recent work, we provide evidence of marked potentiation of statin-induced growth inhibition in mapkdriven melanoma, in combination with small molecule mapk inhibitors. we also present evidence that this effect is mediated by impaired production of isoprenoid farnesyl and geranylgeranyl groups: products of the mevalonate pathway, with downstream effects on both pi3k/akt and hippo signaling. these findings were verified by reintroducing metabolites downstream of hmg-coa reductase, which fully rescues tumor lines’ growth phenotypes. mouse studies of dual therapy with statins and braf inhibitors in the setting of vemurafenib-resistant braf-mutant melanoma provide additional in vivo evidence of efficacy, supporting a possible role for trials of statin and mapk inhibitor combination therapy in human cancer patients. we also used data from the cancer genome atlas to independently analyze correlation of pathway member levels with overall survival. we found that upregulation of farnesyl pyrophosphate synthase (fdps), farnesyl-diphosphate farnesyltransferase (fdft1), mevalonate kinase (mvk), and mevalonate dehydrogenase (mvd) were all significantly skin december 2018 volume 2 supplemental issue copyright 2018 the national society for cutaneous medicine 115 associated with decreased overall survival, highlighting the importance of this pathway to human cancer biology and disease prognosis. references: 1. chapman, p. b., hauschild, a., robert, c., haanen, j. b., ascierto, p., larkin, j., dummer, r., garbe, c., testori, a., maio, m., et al. (2011). improved survival with vemurafenib in melanoma with braf v600e mutation. the new england journal of medicine 364, 2507-16. 2. kang, h. b., fan, j., lin, r., elf, s., ji, q., zhao, l., jin, l., seo, j. h., shan, c., arbiser, j. l., et al. (2015). metabolic rewiring by oncogenic braf v600e links ketogenesis pathway to braf-mek1 signaling. molecular cell. 3. santos, c. r., and schulze, a. (2012). lipid metabolism in cancer. the febs journal 279, 2610-23. 4. sosman, j. a., kim, k. b., schuchter, l., gonzalez, r., pavlick, a. c., weber, j. s., mcarthur, g. a., hutson, t. e., moschos, s. j., flaherty, k. t., et al. (2012). survival in braf v600-mutant advanced melanoma treated with vemurafenib. the new england journal of medicine 366, 707-14. powerpoint presentation real-world treatment and patient-specific characteristics of actinic keratosis in the usa jes b. hansen1, mads d. faurby1, meg corliss2, steven r. feldman3 1leo pharma a/s, ballerup, denmark; 2leo pharma inc, nj, usa; 3department of dermatology, wake forest university school of medicine, nc, usa synopsis methods table 1. provider characteristics conclusions • the chart review provided a level of understanding of how ak lesions are treated in a real-world setting. • a procedure is the most common treatment approach although most patients with ak received a topical treatment. • with more than five ak lesions at baseline, procedure-only treatment became less effective; the opposite effect was seen with topical-only treatment, which showed a higher partial response to treatment with more than five ak lesions. 1. berman b, cockerell cj. j am acad dermatol 2013; 68:s10–19; 2. glogau rg. j am acad dermatol 2000; 42:s23–s24; 3. goldenberg g. jeadv 2017;31 (suppl. 2):12–16. references baseline characteristics • in total, 86 providers provided medical records for 429 patients. • provider characteristics are presented in table 1 and patient baseline characteristics are presented in table 2. phase 1. feasibility assessment • the study was pilot tested with 10 clinics • each provider abstracted six medical records and participated in interviews to assess the functionality of the data collection form and the availability of desired data in the medical records. phase 2. medical record review • this was a retrospective medical record review of information on patients with a diagnosis of ak • the data were fully anonymized, no personal or identifiable information was collected and there was no patient contact or prospective follow-up. provider inclusion criteria • located in the usa • dermatologist or nurse practitioner/physician assistant specializing in dermatology with 3–35 years’ practice experience • treated at least 40 patients with ak in the last year • main decision maker regarding treatment of ak • detailed information provided in the medical record regarding ak. patient inclusion criteria • confirmed diagnosis of ak • treatment initiated between january 1, 2012 and september 30, 2014 • first diagnosis treated during this period was considered the ‘index diagnosis’ • the ak index diagnosis must have met one of the following definitions on the diagnosis date: • ak was new to the anatomical region • ak was new in the patient • new treatment cycle • ≥18 years of age at index diagnosis • received ak-related care from the same provider or treatment center for at least 12 months following the index diagnosis date. study measures physician characteristics • geographic practice region, number of years in practice, current case load of patients with ak. demographic characteristics • gender, age, history of malignancies (prior malignancies versus none). clinical characteristics • anatomical location, number of clinically viable ak lesions, type of lesions, grade of most representative lesion in region, size of treated area (small, <25 cm2 versus large, ≥25 cm2). treatment patterns • receipt of procedure versus topical treatment (with or without procedure), type and number of specific treatments received, treatment response: complete clearance (akclear 100), partial clearance (akclear 75); adverse reactions (ars). safety • ars were more common in the topical group, with 32.0% of patients reporting ≥1 ar. • in the procedural treatment group, 9.4% of patients reported ≥1 ar and in the combination group, 23.2% reported ≥1 ar. • the three most common ars by treatment group are presented in table 3. results acknowledgements and disclosures the study was funded by leo pharma. the authors would like to acknowledge alexandra webster, msc, of imed comms, an ashfield company for medical writing support that was funded by leo pharma, in accordance with good publication practice (gpp3) guidelines. jes b. hansen, mads d. faurby and meg corliss are all employees of leo pharma. steven r. feldman consults for leo pharma. total total provider sample, n (%) 86 (100.0) mean number of patients with ak treated in the past year (sd) 482.1 (328.1) mean number of years in practice (sd) 13.8 (6.4) medical speciality, n (%) dermatologist 67 (77.9) nurse practitioner specializing in dermatology 8 (9.3) physician assistant specializing in dermatology 11 (12.8) ultraviolet exposure in region of primary practice*, n (%) high exposure 46 (53.5) low exposure 40 (46.5) practice location, n (%) urban 43 (50.0) suburban 43 (50.0) *physicians were asked to select the metropolitan region in which they practiced; ak, actinic keratosis; sd, standard deviation procedure (n=171) topical (n=150) combination (n=108) sex, n (%) male 108 (63.2) 101 (67.3) 79 (73.2) female 63 (36.8) 49 (32.7) 29 (26.9) mean age at index diagnosis, n (sd) 60.3 (12.1) 58.3 (13.0) 61.5 (11.9) fitzpatrick classification of skin type at index date, n (%) i – always burns, never tans (pale white skin) 43 (25.1) 31 (20.7) 20 (18.5) ii – always burns easily, tans minimally (white skin) 100 (58.5) 78 (52.0) 71 (65.7) iii – burns moderately, tans uniformly (light brown skin) 18 (10.5) 27 (18.0) 15 (13.9) iv – burns minimally, always tans well (moderate brown skin) 8 (4.7) 9 (6.0) 2 (1.9) v – rarely burns, tans profusely (dark brown skin) 1 (0.6) 2 (1.3) 0 (0) undetermined/don’t know 1 (0.6) 3 (2.0) 0 (0) history of malignancies prior to the index ak, n (%) 59 (34.5) 51 (34.0) 41 (38.0) mean number of baseline lesions (sd) 6.1 (7.5) 6.3 (7.8) 7.5 (8.6) field size, n (%) small (<25 cm2) 122 (84.7) 86 (65.7) 55 (77.5) large (≥25 cm2) 20 (13.9) 32 (24.4) 16 (22.5) unknown 2 (1.4) 13 (9.9) 0 (0) ak thickness (ogs), n (%) grade i – mild 63 (43.8) 53 (40.5) 20 (28.2) grade ii – moderate 53 (36.8) 56 (42.8) 46 (64.8) grade iii – severe 7 (4.9) 7 (5.3) 4 (5.6) ogs was not recorded 21 (14.6) 15 (11.5) 1 (1.4) ak, actinic keratosis; ogs, olsen grading scale; sd, standard deviation table 2. patient baseline characteristics treatment pattern • the number of patients that received a procedure to treat the index diagnosis was 171 (39.9%), while 150 (35.0%) patients received topical treatment, and 108 (25.2%) received a combination of procedural and topical treatments. • patients receiving each treatment type, based on if they had 1–5 baseline lesions or ≥6 baseline lesions, are shown in figure 1. figure 1. treatment received by number of baseline lesions 70.8% 64.1% 59.2% 29.2% 35.9% 40.8% procedure topical combination p er ce nt ag e of p at ie nt s (% ) 1–5 baseline lesions ≥6 baseline lesions figure 3. percentage of patients achieving different levels of clearance per treatment group figure 2. treatment cycles per index lesion figure 4. percentage of patients achieving different levels of clearance per treatment group and by number of baseline lesions figure 5. percent reduction in number of baseline lesions by treatment group: (a) procedure, (b) topical, and (c) combination a) b) • the treatment cycles for the index diagnosis are shown in figure 2. efficacy • the response to treatment was known for 249 of 429 patients included in the medical chart review. • thirty-eight (37.6%) patients receiving procedural treatment achieved akclear 100 and 63 (62.4%) achieved akclear 75. twenty-two (25.0%) and 54 (61.4%) patients receiving topical treatment achieved akclear 100 and akclear 75, respectively. eleven (18.3%) and 34 (56.6%) patients receiving combination achieved akclear 100 and akclear 75, respectively. percent clearance by treatment group is shown in figure 3. • no patients with >5 baseline ak lesions (n=29) receiving a procedure achieved akclear 100; 9.7% of patients receiving topical treatment (n=31) achieved akclear 100. percent clearance by number of baseline lesions and by treatment group is shown in figure 4. • as number of baseline lesions increased, procedure treatment became less effective (figure 5a); the opposite trend was seen with topical treatment (figure 5b). a similar result to topical treatment was observed with combination treatment (figure 5c). procedure (n=171) topical (n=150) combination (n=108) total number of patients reporting an ar, n (%) 16 (9.4) 48 (32.0) 25 (23.2) total number of ars reported 24 82 55 three most commonly reported ars by treatment group* pain 10 (41.7) 0 4 (7.0) blistering 7 (29.2) 0 2 (4.0) erythema 1 (4.2) 40 (48.8) 20 (36.0) headache 4 (16.7) 0 (0) 0 pruritus 1 (4.2) 18 (22.0) 8 (15.0) edema 0 12 (14.6) 2 (4.0) dermatitis 0 6 (7.3) 9 (16.0) *most commonly reported ars are shown as a percentage of the total ars reported; ar, adverse reaction table 3. most commonly reported ars by treatment group objective to describe and understand real-world treatment patterns, and patient-specific characteristics of actinic keratosis (ak) in the usa. background: actinic keratosis (ak) is a sun-damage-induced field disease, which manifests as clinical and subclinical lesions.1 if left untreated, ak may progress to squamous cell carcinoma.2 multiple treatment options are available.3 study description: a retrospective medical chart review first determined what information related to ak was available in us patient records by 10 providers treating ak in a feasibility phase. thereafter a total of 86 providers across the us provided medical records for 429 patients with a diagnosis of ak during a period of 12 months. the results were analyzed descriptively. results: the mean (sd) age at index ak diagnosis was 59.9 (±12.4) years. the olsen grading scale (ogs) at baseline was ogs i for 136 patients (44.0%); 155 patients (50.2%) had ogs ii and 18 patients (5.8%) had ogs iii. in the first treatment cycle, 218 patients received a procedure (cryotherapy, phototherapy or mohs surgery), 162 received topical therapy, and 49 had a combination of procedure and topical. a second treatment cycle was not initiated within the 12 months for 116 (53.2%) patients receiving a procedure in the first treatment cycle, 106 (65.4%) receiving topical therapy, and 23 patients (46.9%) treated with combination therapy. independent of the number of treatment cycles during the study period, 171 patients (39.9%) received a procedure to treat the ak index diagnosis, 150 (35.0%) received topical therapy, and 108 (25.2%) received a combination of procedure and topical. efficacy assessment was based on the best response to treatment independent of the number of treatment cycles. complete and partial clearance were achieved by 37.6% and 62.4% of patients treated with procedure, 25.0% and 61.4% treated with topical, and 18.3% and 56.6% treated with a combination of procedure and topical. for patients with more than five ak lesions at baseline, complete and partial clearance were achieved by 0% and 44.8% receiving a procedure (n=29) and 9.7% and 71% treated with topicals (n=31). conclusion: this chart review study, although with limitations, provides a level of understanding of how ak lesions are treated in a real-world setting. a procedure alone is the most common treatment approach, though most patients with ak received a topical treatment. with more than five ak lesions at baseline, procedure-only treatment became less effective; the opposite effect was seen with topical-only treatment, which showed a higher partial response to treatment with more than five ak lesions. procedure (n=63, 28.9%) combination (n=5, 2.3%) topical (n=34, 15.6%) none (n=116, 53.2%) procedure (n=12, 7.4%) topical (n=44, 27.2%) none (n=106, 65.4%) procedure (n=23, 47.9%) combination (n=2, 4.2%) topical (n=1, 2.1%) none (n=22, 45.8%) none (n=1, 100.0%) first treatment second treatment topical (n=162) procedure (n=218) combination (n=48) procedure, topical, and other (n=1) 37.6% 25.0% 18.3% 24.8% 36.4% 38.3% 37.6% 38.6% 43.3% 0 20 40 60 80 100 procedure topical combination p er ce nt ag e of p at ie nt s 100% clearance 75–99% clearance 0–74% clearance 59.3% 36.4% 9.7% 17.9% 25.0% 11.9% 44.8% 20.5% 61.3% 25.0% 50.0% 28.8% 55.2% 43.2% 29.0% 57.1% 25.0% 0 20 40 60 80 100 procedure 1–5 procedure ≥6 topical 1–5 topical ≥6 combination 1–5 combination ≥6 p er ce nt ag e of p at ie nt s 100% clearance 75–99% clearance 0–74% clearance % shown in the second treatment cycle is the percentage of total patients from the first treatment cycle p er ce nt r ed uc tio n 0 20 40 60 80 100 0 10 20 30 40 number of baseline lesions 0 20 40 60 80 100 0 10 20 30 40 50 60 number of baseline lesions p er ce nt r ed uc tio n c) 0 20 40 60 80 100 0 10 20 30 40 number of baseline lesions p er ce nt r ed uc tio n 100 80 60 40 20 0 �� real-world treatment and patient-specific characteristics of actinic keratosis in the usa � skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 273 original research reporting of quality of life in clinical trials of biologics for plaque psoriasis: a systematic review giselle prado mda, anna nichols mdb, phd, mercedes florez-white mdc, francisco kerdel bsc, mbbsc,d anational society for cutaneous medicine, new york, ny bdepartment of dermatology & cutaneous surgery, university of miami miller school of medicine, miami, fl cdepartment of dermatology, herbert wertheim college of medicine, florida international university, miami, fl dflorida academic dermatology center, coral gables, fl psoriasis vulgaris is a chronic relapsing and remitting inflammatory skin disease that affects 0.5-11.43% of the population worldwide.1 psoriasis negatively impacts patients’ quality of life.2,3 for many patients, improved quality of life is as important as objective clinical improvement of psoriasis lesions.4 many different tools have been created to evaluate the effect of chronic skin conditions on quality of life (e.g. dermatology life quality index, skindex, sf-36, among others). the dermatology life quality index (dlqi) was first reported in 1994 and is a validated tool used to assess the effect of dermatologic conditions on quality of life.5,6 it is the most commonly used quality of life abstract background: psoriasis is a chronic remitting and relapsing skin disease. for many patients, improved quality of life (qol) is as important as clinical improvement of lesions. objective: to review reporting of dermatology life quality index (dlqi) in randomized controlled trials (rcts) of biologics for adult patients with plaque psoriasis. methods: a systematic review was conducted in 4 databases for rcts that measured dlqi at baseline and endpoint. a data collection form was created for collecting study variables. risk of bias was assessed using the cochrane risk of bias tool. results: thirty-four rcts enrolling 16,784 patients were included. complete baseline and final mean dlqi data was retrieved for 24 studies (70.6%). the mean dlqi at baseline was reported in 79.4% of rcts. the median at baseline was reported in 14.7% of rcts. the mean dlqi at endpoint was reported in 23.5% of rcts and the median dlqi at endpoint was reported in 5.9% of rcts. the mean change in dlqi was reported in 64.7% of rcts. conclusions: dlqi was measured in most clinical trials assessing the efficacy of biologics for psoriasis. studies did not adhere to uniform standards in publishing results, making analysis of the impact on dlqi challenging. introduction https://www.google.com/maps/place/florida+academic+dermatology+centers/@25.763526,-80.25912,3a,75y,259h,90t/data=!3m7!1e1!3m5!1sg4ehzz2ry9iwiwz-cq6oaw!2e0!6s%2f%2fgeo0.ggpht.com%2fcbk%3fcb_client%3dmaps_sv.tactile%26output%3dthumbnail%26thumb%3d2%26panoid%3dg4ehzz2ry9iwiwz-cq6oaw%26w%3d374%26h%3d75%26yaw%3d259%26pitch%3d0%26thumbfov%3d120%26ll%3d25.763525,-80.259120!7i13312!8i6656!4m7!1m4!3m3!1s0x88d9b775db0c5ffb:0x13f1ff27e25b3882!2s836+ponce+de+leon+blvd,+coral+gables,+fl+33134!3b1!3m1!1s0x88d9b775db0c5ffb:0x6f3711e95685ddb9!6m1!1e1 skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 274 measure in clinical trials in dermatology.7 the dlqi is widely used due to its simplicity in scoring, quick completion in 2 minutes, among other reasons.8-10 the dlqi uses 10 questions to assess the effect of a skin condition on a patient’s symptoms and feelings, daily activities, leisure activities, work and school, personal relationships, and treatment.5 respondents have the ability to rate the effect on quality of life as “not at all”, “a little”, “a lot”, and “very much.” this in turn is scored from 0-3 for each of the 10 questions for a total possible score of 30 points. these summary scores can be banded into different levels of severity. a summary score of 0-1 signifies no effect on quality of life, 2-5 a small effect, 6-10 a moderate effect, 11-20 a very large effect, and 21-30 an extremely large effect.11 biologic therapy can lead to improvements in quality of life that are both statistically significant and clinically significant as seen when the banding concept of dlqi scores is applied.11 thus, improving quality of life in patients with psoriasis should be of the utmost importance to clinicians. there are a variety of treatment options for moderate to severe plaque psoriasis and biologics have revolutionized the management of this disease. for patients with psoriasis treated with biologic therapy, there is a clear correlation between dlqi and pasi scores.12 at the time of writing this manuscript, six biologic medications were approved by the united states food and drug administration (fda) for use in plaque psoriasis: adalimumab, etanercept, infliximab, ixekizumab, secukinumab, and ustekinumab. the use of these biologics for psoriasis is supported by data from randomized clinical trials (rcts). other reviews have examined the effect of biologic therapy on quality of life.13,14 however, new drugs have been approved since the prior studies were published and many of the originally approved drugs have been withdrawn from the market. this review presents an updated assessment of quality of life studies in psoriasis. data sources: we searched four computerized bibliographical databases for articles published since inception to august 2016: pubmed, cochrane library central, ovid medline, and embase. search terms included: “quality of life,” “dlqi,” “dermatology life quality index,” “dermatology quality of life index,” “psoriasis,” “randomized controlled trials,” “biologic therapy,” “biologic,” and the generic names for each of the drugs. the search was restricted to publications in english. this systematic review followed the preferred reporting items for systematic reviews and meta-analyses (prisma) guidelines (prospero registration no. crd42016046523). the search strategy used is given in appendix 1. we reviewed trial registers (clinicaltrials.gov) and searched grey literature. reference lists of all included studies and of recent reviews were also assessed. electronic publications in advance of print were also included. inclusion criteria: we included double-blind, rcts of patients with plaque psoriasis treated with fda approved biologic treatments that measured dlqi at baseline and endpoint in adults (aged >18 years). exclusion criteria: the exclusion criteria were as follows: trials that included only a subtype of psoriasis, trials that only randomized patients with methods skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 275 concomitant psoriatic arthritis, studies that included any patient less than 18 years of age, articles where the change in dlqi values from baseline to endpoint could either not be reliably calculated or could not be obtained after requesting additional information from the author or study sponsor, and abstracts and posters where further data were not available upon contacting the author. outcome measures: the primary outcome recorded was the mean dlqi score at baseline and endpoint. for studies with an open-label extension, the data were extracted only for the period of the study while it was randomized and controlled. for crossover trials, the data were extracted prior to the crossover. data extraction and synthesis: one reviewer (g.p.) extracted data, another reviewer (a.n.) checked the extracted data for accuracy, and the reviewers met to discuss any disagreements. we created and piloted a data collection form for recording study design, dlqi scores, drug administered, dosing schedule, and quality of the methodology. risk of bias was assessed using the cochrane risk of bias tool independently by 2 reviewers (g.p. and a.n.). disagreements were resolved by discussion. after screening 571 records, we identified 34 rcts enrolling a total of 16,784 patients published between december 2003 and may 2016 that fit our inclusion and exclusion criteria. for these studies, 38 articles were retrieved, including those related to the original rct publication as well as subanalyses of the original rct. of the 34 original rcts included, complete data, meaning baseline and final mean dlqi scores, was retrieved for 24 studies (70.6%). of these 24 studies, 66.7% present unpublished data obtained from study authors and sponsors after contacting them for additional information. the mean dlqi at baseline was reported in 79.4% of studies (table 1). the median at baseline was reported in 14.7% of the studies. the mean dlqi at endpoint was only reported in 23.5% of studies and the median dlqi at endpoint was reported in 5.9% of studies. the mean change in dlqi was reported in 64.7% of studies. adalimumab. there were five rcts comprising 1,918 patients that assessed dlqi data in patients treated with adalimumab. of these studies, we obtained complete data for four rcts (80%). the dlqi for the placebo group ranged from 8.414.6 at baseline and 7.6-12.3 at endpoint. for those treated with adalimumab, the mean dlqi ranged from 8.4-14.6 at baseline and 2.0-5.0 at endpoint. etanercept. there were eight rcts comprising 2,968 patients that assessed dlqi data in patients treated with etanercept. of these studies, we obtained complete data for four rcts (50%). the dlqi for the placebo group ranged from 12.2-14 at baseline and 9.75-12.3 at endpoint. for those treated with etanercept, the mean dlqi ranged from 10-13.87 at baseline and 3.8-5.8 at endpoint. infliximab. there were five rcts comprising 1,639 patients that assessed dlqi data in patients treated with infliximab. of these studies, we obtained complete data for four rcts (80%). the dlqi for the placebo group ranged 10.5-14.4 at baseline and 11.2-13.1 at endpoint. for those treated with infliximab, the mean dlqi ranged from results skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 276 12.3-14.4 at baseline and 2.4-6.5 at endpoint. ixekizumab. there were four rcts comprising 4,008 patients that assessed dlqi data in patients treated with ixekizumab. of these studies, we obtained complete data for all 4 rcts (100%). the dlqi for the placebo group ranged from 10.81-12.8 at baseline and 10.26-11.6 at endpoint. for those treated with ixekizumab, the mean dlqi ranged from 10.36-13.4 at baseline and 1.9-4.66 at endpoint. secukinumab. there were five rcts comprising 3,294 patients that assessed dlqi data in patients treated with secukinumab. of these studies, we obtained complete data for 2 rcts (40%). the dlqi for the placebo group ranged from 12.0-13.4 at baseline and 10.9-11.5 at endpoint. for those treated with secukinumab, the mean dlqi ranged from 11.3-13.9 at baseline and 2.5-3.7 at endpoint. ustekinumab. there were seven rcts comprising 2,957 patients that assessed dlqi data in patients treated with ustekinumab. of these studies, we obtained complete data for 6 rcts (85.7%). the dlqi for the placebo group ranged from 10.5-15.2 at baseline and 9.7-14.7 at endpoint. for those treated with ustekinumab, the mean dlqi ranged from 10.5-16.1 at baseline and 2.1-4.8 at endpoint. quality of evidence for included studies. appendix 2 provides an assessment of the risk of bias for the included studies. all studies were randomized controlled trials. most studies limited the bias inherent to the trial by employing the use of random sequence generation, allocation concealment, and blinding of participants, personnel, and assessors. skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 277 table 1: summary of clinical trials investigating biologic therapy for patients with plaque psoriasis. source clinicaltrials .gov number interventions trial phase tx endpoint week no. of pbo pts at base -line no. of pbo pts at endpoint no. of tx pts at base -line no. of tx pts at endpoint dlqi measurement reported in publication doses studied mean dlqi ± sd (se) pbo tx baseline endpoint baseline endpoint asahina 201026 nct003387 54 adalimumab vs. pbo 2/3 16 & 24 138 138 123 122 mean at baseline mean change score with sd 40mg eow 8.4 n/a 8.4 n/a 80mg at baseline then 40mg eow 8.4 n/a 8.5 n/a 80mg eow 8.4 n/a 8.8 n/a gordon 201527* nct014835 99 adalimumab vs. guselkumab vs. pbo 2 16 42 42 43 39 mean change score with sd 80mg at baseline then 40mg eow 14.6 ± 5.91 12.3 ± 7.66 14.6 ± 7.17 5.0 ± 7.41 shikiar 200728/ wallace 200529 n/a adalimumab vs. pbo 2 12 104 104 95 94 mean at baseline and endpoint with 95% ci mean change score with 95% ci 80mg at baseline then 40mg eow 12.2 (10.014.4) 10.7 (9.112.4) 13.3 (10.715.8) 2.8 (1.04.7) 80mg at baseline then 40mg/wk 12.2 (10.014.4) 10.7 (9.112.4) 13.6 (11.315.9) 2.0 (0.33.8) revicki 200830 nct002358 20 adalimumab vs. mtx vs. pbo 3 12 & 16 53 53 108 103 mean at baseline and endpoint with sd 80mg at baseline then 40mg 11.7 ± 7.0 7.6 ± 6.4 11.8 ± 6.6 2.5 ± 4.0 skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 278 mean change score with 95% ci eow revicki 200731 nct002378 87 adalimumab vs. pbo 3 4 & 16 398 397 814 808 mean at baseline and endpoint with sd mean change score with 95% ci 80mg at baseline then 40mg eow 11.4 ± 7.0 9.2 ± 7.1 11.3 ± 6.6 3.0 ± 4.5 bachele z 201532/ valenzu ela 201633* nct012415 91 etanercept vs. tofacitinib vs. pbo 3 12 108 107 336 335 mean at baseline and with sd and se no. of pts with clinically meaningful decrease in dlqi 50mg twice/ wk 12.3 ± 7.1 10.3 12.7 ± 6.8 3.8 strober 201134* nct007105 80 etanercept vs. briakinumab vs. pbo 3 12 72 66 139 127 no. of pts with dlqi=0 at baseline and endpoint 50mg twice/ wk 13.61 ± 6.918 10.73 ± 6.9464 13.87 ± 7.848 4.78 ± 5.497 leonardi 200335 n/a etanercept vs. pbo 2 12 & 24 166 166 486 486 mean at baseline with se % change with se at wk 12 and 24 25mg / wk 12.8 (0.6) n/a 12.2 (0.5) n/a 25mg twice/ wk 12.8 (0.6) n/a 12.7 (0.5) n/a 50mg twice/wk 12.8 (0.6) n/a 11.3 (0.5) n/a skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 279 gottlieb 200336/ lowe 200237 n/a etanercept vs. pbo 3 12 & 24 55 55 57 57 mean at baseline % change with se at wk 24 25mg twice/ wk 14 n/a 10 n/a krueger 200538 n/a etanercept vs. pbo 3 12 193 193 390 390 mean at baseline with sd no. of pts with clinically meaningful decrease in dlqi graphical representation of % change 50mg / wk 12.2 ± 6.8 n/a 11.5 ± 7.2 n/a 50mg twice/wk 12.2 ± 6.8 n/a 11.4 ± 6.5 n/a tyring 200639 nct001114 49 etanercept vs. pbo 3 12 307 307 311 311 mean at baseline with sd % change at wk 12 50mg twice/wk 12.5 ± 6.7 n/a 12.1 ± 6.7 n/a reich 200940 n/a etanercept vs. pbo 3 12 45 46 94 96 mean at baseline and endpoint mean change score % change at wk 12 graphical 50mg / wk 13.6 12.3 13.2 5.8 skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 280 representations of response ranges at baseline and endpoint, % of pts with dlqi= 0 or 1, and % of pts with clinically meaningful decrease in dlqi gottlieb 201141* nct006919 64 etanercept vs. briakinumab vs. pbo 3 12 68 68 141 141 no. of pts with dlqi=0 at baseline and endpoint 50mg twice/wk 13.05 9.75 12.40 4.39 feldman 200542/ gottlieb 200443 n/a infliximab vs. pbo 2 10 51 51 198 198 mean at baseline and endpoint with sd median at baseline and endpoint with iqr mean change score with sd % change at wk 10 with sd 3mg/kg at wk 0, 2 , and 6 13.8 ± 6.6 11.2 ± 7.4 12.3 ± 7.3 3.4 ± 5.2 5mg/kg at wk 0, 2 , and 6 13.8 ± 6.6 11.2 ± 7.4 13.2 ± 7.0 2.8 ± 5.0 feldman 200844/ menter 200745* n/a infliximab vs. pbo 2 10 208 200 625 619 mean at baseline with sd mean change 3mg/kg at wk 0, 2 , and 6 13.4 ± 7.34 12.8 ± 7.46 12.8 ±6.89 3.3 ± 4.87 5mg/kg at 13.4 ± 12.8 ± 13.1 2.5 ± skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 281 score with sd median at baseline graphical representations of median change score, % of pts with dlqi=0 at endpoint wk 0, 2 , and 6 7.34 7.46 ±7.01 3.83 yang 201246 nct011778 00 infliximab vs. pbo 3 10 45 44 84 82 mean at baseline and endpoint with sd mean change score with sd graphical representation of mean scores 5mg/kg at wk 0, 2 , and 6 14.4 ± 6.3 13.1 ± 5.7 14.4 ± 6.2 6.5 ± 6.5 torii 201047 n/a infliximab vs. pbo 3 10 & 14 19 16 35 34 mean at baseline with sd median at baseline mean change score with sd no. of pts with dlqi=0 at 5mg/kg at wk 0, 2 , and 6 10.5 ± 6.8 n/a 12.7 ± 6.8 n/a skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 282 endpoint no. of pts with clinically meaningful decrease in dlqi graphical representation of mean change scores with sd reich 200648* nct011778 00 infliximab vs. pbo 3 10 & 24 77 75 297 291 mean at baseline with sd mean change score with sd graphical representation of % of pts with dlqi=0 at endpoint, response ranges at baseline and endpoint 5mg/kg at wk 0, 2, 6, then every 8 wk 11.8 ± 7.46 11.3 ± 8.10 12.7 ± 6.97 2.4 ± 4.16 griffiths 201549* nct015972 45 ixekizumab vs. etanercept vs. pbo 3 12 168 168 i: 698 e: 358 i: 698 e: 358 mean at baseline with sd mean change score with se no. of pts with ixekizumab 160mg at baseline then 80mg eow 12.8 ± 7.24 10.6 ± 7.34 12.4 ± 6.86 1.9 ± 3.12 ixekizumab 160mg at 12.8 ± 7.24 10.6 ± 7.34 11.6 ± 6.65 2.6 ± 4.48 skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 283 dlqi=0 at endpoint baseline then 80mg e4w etanercept 50mg twice/wk 12.8 ± 7.24 10.6 ± 7.34 12.7 ± 7.03 4.7 ±5.35 griffiths 201549* nct016461 77 ixekizumab vs. etanercept vs. pbo 3 12 193 193 i: 771 e: 382 i: 771 e: 382 mean at baseline with sd mean change score with se no. of pts with dlqi=0 at endpoint ixekizumab 160mg at baseline then 80mg eow 12.7 ± 7.0 10.5 ± 7.23 12.4 ± 6.93 2.0 ± 3.30 ixekizumab 160mg at baseline then 80mg e4w 12.7 ± 7.0 10.5 ± 7.23 11.9 ± 6.97 2.4 ± 4.25 etanercept 50mg twice/wk 12.7 ± 7.0 10.5 ± 7.23 11.5 ± 6.84 3.8 ± 4.75 leonardi 201250* nct011074 57 ixekizumab vs. pbo 2 16 27 27 115 115 mean at baseline with sd mean change score with sd % of pts with dlqi=0 at endpoint 10 mg at wk 0, 2, 4, 8, 12, 16 10.81 ± 5.21 10.26 ± 6.92 10.61 ± 7.16 4.54 ± 6.04 25 mg at wk 0, 2, 4, 8, 12, 16 10.81 ± 5.21 10.26 ± 6.92 11.63 ± 7.19 4.66 ± 6.47 75 mg at wk 0, 2, 4, 8, 12, 16 10.81 ± 5.21 10.26 ± 6.92 11.10 ± 5.59 1.96 ± 3.27 150 mg at wk 0, 2, 4, 8, 12, 16 10.81 ± 5.21 10.26 ± 6.92 10.36 ± 5.81 2.15 ± 3.30 gordon 201551* nct014745 12 ixekizumab vs. pbo 3 12 431 431 865 865 none in abstract 160mg at baseline 12.8 ± 7.11 11.6 ± 7.53 13.4 ± 7.02 2.0 ± 3.33 skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 284 then 80mg eow 160mg at baseline then 80mg e4w 12.8 ± 7.11 11.6 ± 7.53 13.2 ± 7.02 2.3 ± 3.87 augustin 201652 nct009410 31 secukinuma b vs. pbo 2 12 67 58 337 322 mean at baseline with sd median at baseline and endpoint with iqr graphical representation of % of pts with dlqi= 0 or 1 150mg at baseline 12.5 ± 6.2 n/a 11.3 ± 6.9 n/a 150mg at baseline then e4w 12.5 ± 6.2 n/a 11.8 ± 7.1 n/a 150mg at baseline then wk 1, 2, and 4 12.5 ± 6.2 n/a 11.8 ± 6.7 n/a thaci 201553/ blauvelt 201654 nct020749 82 secukinuma b vs. ustekinuma b 3 16 s: 331 u: 333 s: 331 u: 333 no. of pts with dlqi=0 or 1 at endpoint secukinum ab 300mg weekly for wk 0-4 then e4w 13.4 ± 7.63 n/a ustekinuma b 45 or 90mg at baseline, wk 4, then every 12 wk 13.2 ± 7.57 n/a langley 201455 nct013654 55 secukinuma b vs. pbo 3 12 248 246 490 488 mean at baseline and endpoint mean change 300mg weekly for wk 0-4 then e4w 12.0 10.9 13.9 2.5 skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 285 score 150mg weekly for wk 0-4 then e4w 12.0 10.9 13.4 3.3 langley 201455 nct013585 78 secukinuma b vs. etanercept vs. pbo 3 12 326 324 980 973 mean at baseline and endpoint mean change score secukinum ab 300mg weekly for wk 0-4 then e4w 13.4 11.5 13.3 2.9 secukinum ab 150mg weekly for wk 0-4 then e4w 13.4 11.5 13.4 3.7 etanercept 50mg twice/wk 13.4 11.5 13.4 5.5 paul 201556 nct016366 87 secukinuma b vs. pbo 3 12 61 61 121 121 paper did not report any dlqi data but dlqi was measured according to protocol on clinicaltrials.gov 300mg weekly for wk 0-4 then e4w n/a n/a n/a n/a 150mg weekly for wk 0-4 then e4w n/a n/a n/a n/a leonardi 200857* nct002679 69 ustekinuma b vs. pbo 3 12 255 252 511 503 mean at baseline with sd mean change score with sd median change score with iqr 45mg at baseline and wk 4 11.8 ± 7.41 11.2 ± 7.45 11.1 ± 7.09 3.1 ± 4.26 90mg at baseline and wk 4 11.8 ± 7.41 11.2 ± 7.45 11.6 ± 6.92 2.8 ± 3.64 skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 286 no. of pts with dlqi=0 or 1 at endpoint papp 200858* nct003074 37 ustekinuma b vs. pbo 3 12 410 400 820 803 mean at baseline with sd mean change score with sd median change score with iqr no. of pts with dlqi=0 or 1 at endpoint 45mg at baseline and wk 4 12.3 ± 6.86 11.8 ± 7.77 12.2 ± 7.07 2.9 ± 4.35 90mg at baseline and wk 4 12.3 ± 6.86 11.8 ± 7.77 12.6 ± 7.29 2.7 ± 4.01 igarashi 201259 nct007235 28 ustekinuma b vs. pbo 2/3 12 32 31 126 123 mean at baseline with sd mean change score with sd median change score no. of pts with dlqi=0 or 1 at endpoint 45mg at baseline and wk 4 10.5 ± 6.2 n/a 11.4 ± 6.5 n/a 90mg at baseline and wk 4 10.5 ± 6.2 n/a 10.7 ± 6.4 n/a krueger 200760* nct003202 16 ustekinuma b vs. pbo 2 12 64 64 256 255 mean at baseline with sd mean change score with sd 45mg at baseline 12.0 ± 7.25 9.7 ± 7.10 11.9 ± 6.99 4.5 ± 6.24 90mg at baseline 12.0 ± 7.25 9.7 ± 7.10 13.4 ± 7.25 3.6 ± 5.10 45mg 12.0 ± 9.7 ± 12.6 ± 2.5 ± skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 287 median change score with iqr no. of pts with dlqi=0 at endpoint weekly for 4 wk 7.25 7.10 6.63 3.75 90mg weekly for 4 wk 12.0 ± 7.25 9.7 ± 7.10 10.5 ± 6.73 2.1 ± 4.01 zhu 201361* nct010089 95 ustekinuma b vs. pbo 3 12 162 159 160 158 mean at baseline with sd mean change score with sd 45mg at baseline and wk 4 13.1 ± 7.51 11.2 ± 7.88 13.7 ± 7.57 4.4 ± 5.39 tsai 201162* nct007473 44 ustekinuma b vs. pbo 3 12 60 60 61 59 mean at baseline with sd mean change score with sd median change score with iqr 45mg at baseline and wk 4 15.2 ± 6.95 14.7 ± 7.97 16.1 ± 6.09 4.8 ± 5.25 papp 201663* nct020544 81 ustekinuma b vs. risankizuma b 12 & 24 40 40 median at baseline median % change at wk 12 % of pts with dlqi=0 or 1 at wk 24 45 or 90mg at baseline, wk 4, wk 16 15.8 ± 6.5 2.8 ± 4.3 abbreviations: week of treatment endpoint used for endpoint columns denoted in bold. *denotes trials for which additional unpublished data was obtained after contacting authors and study sponsors. skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 288 &: and eow: every other week. e4w: every 4 weeks. iqr: interquartile range. mtx: methotrexate. n/a: not available. : not applicable. sd: standard deviation. se: standard error. pbo: pbo pts: patients. tx: treatment. wk: week. skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 289 psoriasis can have a comparable negative effect on quality of life as cancer, myocardial infarction, and chronic lung disease.3 patients with psoriasis have decreased work productivity, increased incidence of depression, and difficulties in personal relationships.15-17 patients with more severe disease manifestations have even greater impairment in these areas of life.18 this disease results in cumulative life course impairment that influences how patients make major life decisions, develop social relationships, and pursue their life goals.19 achieving significant improvements in quality of life measures should be the goal for any clinical trial assessing treatment efficacy in patients with psoriasis. it has previously been shown that biologic therapy significantly improves dlqi compared to conventional systemic therapy.20 most clinical trials define efficacy and safety as primary endpoints and relegate quality of life measures as secondary endpoints. this systematic review demonstrates a clear improvement in quality of life, as evidenced by reductions in dlqi scores for patients with plaque psoriasis treated with biologics. the first generation of biologic therapies for plaque psoriasis were the tnf-alpha inhibitors (adalimumab, etanercept, and infliximab). more recently, the targeted therapies against interleukin (il)-17 and il12/23 have heralded a new era of biologic therapies. although there were slight differences between the endpoint scores for the tnf-alpha inhibitors and the newer biologics, it is not clear whether these slight differences correspond to clinically significant differences in quality of life. comparing the ranges of dlqi scores reported across the different drugs, most patients reported a “small effect” of their psoriasis symptoms on quality of life after treatment. when discussing improvement in quality of life, it is important to keep in mind the concept of minimal clinically important difference (mcid). mcid is defined as “the smallest difference in score in the domain of interest which patients perceive as beneficial and which would mandate, in the absence of troublesome side effects and excessive cost, a change in the patient’s management.”21 taken from the patient’s perspective, this may mean a significant improvement in quality of life and symptomatology; while taken from the clinician’s perspective, this may mean a significant improvement in the treatment or prognosis of the disease. several studies using different methodologies have attempted to determine the minimum clinically important change in dlqi score and results have ranged from 3-5.22 four studies included in this review reported some measure of patients who achieved a meaningful decrease in dlqi (either number or percentage of patients). it is possible that the dlqi may not be the best quality of life metric for patients with psoriasis. the dlqi is a scale used to objectively quantify the effect of dermatologic conditions on quality of life. it was surprising to note that there were no significant differences in dlqi scores among the different biologic drugs. most biologic drugs achieved a final dlqi of 2-5 after starting at a baseline of 8-14. the most recent clinical trials tout major differences in pasi scores as evidence for the efficacy of certain drugs over others. this difference in efficacy was not evident when looking at dlqi in isolation. the dlqi instrument as a measure of quality of life may not be discussion skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 290 sensitive enough to detect minor improvements attributable to increased skin clearance and then translate these improvements to effects on quality of life. considering the minor differences in final dlqi scores among the different medications, it is important to keep in mind economic costs when prescribing a biologic therapy. the annual costs of these drugs range from $30,001 for infliximab to $69,762 for ixekizumab.23 older tnf-alpha inhibitors such as adalimumab and etanercept are less expensive than the newer specific il inhibitors. there are limited healthcare resources available and many patients struggle to afford their medications, therefore it is reasonable to utilize more affordable medications given the comparable effects on quality of life. a recent meta-analysis found no difference in risk of serious infections among different biologic therapies.24 however, newer medications offer less frequent dosing schedules, which can also augment perceived quality of life for patients. our systematic review was extensive with a precisely executed search strategy and selection process. it serves as an up to date resource for quality of life data in clinical trials of psoriasis. the last similar review was published in 2006 with several drugs that are not currently available in the u.s.13 additionally, the studies included in our review were all randomized controlled trials that are less susceptible to sources of bias. our systematic review has some limitations. first, there was significant heterogeneity among the included studies in terms of length of study, characteristics of enrolled patients, and biologic therapy protocol. these studies were conducted with different objectives and comparison treatments across different trials. although we originally planned to conduct a meta-analysis that would allow us to combine the results across several trials for each drug and thus compare drugs to one another, this proved to be impossible due to significant heterogeneity. since we were unable to conduct the meta-analysis, it is not clear which drug is the most effective at improving quality of life. future studies should determine whether clinically significant differences in quality of life (keeping in mind efficacy and cost-effectiveness) exist between the studied drugs. second, most studies did not uniformly report dlqi data. in these cases, significant efforts were made to contact study authors and sponsoring companies for additional information. many complied with our requests for further information. however, several study sponsors declined to provide unpublished data for use in this study. poor reporting of quality of life data continues to be a significant problem in dermatology research25 and others have had similar experiences in which a lack of reporting guidelines for quality of life data resulted in data analysis difficulties.7 conflict of interest disclosures: dr. kerdel receives honoraria from amgen, abbvie, janssen, lilly, celgene, actelion, novartis, leo, regeneron, sanofi, and valeant. he also receives research grants from amgen, abbvie, janssen, lilly, celgene, actelion, novartis, pfizer, regeneron, sanofi, ucb, and astrozeneca. funding: none. corresponding author: giselle prado, md national society for cutaneous medicine, new york, ny drgiselleprado@gmail.com skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 291 references: 1. michalek im, loring b, john sm. a systematic review of worldwide epidemiology of psoriasis. j eur acad dermatol venereol. 2016; 2. de arruda lh, de moraes ap. the impact of psoriasis on quality of life. br j dermatol. 2001;144 suppl 58:33-6. 3. rapp sr, feldman sr, exum ml, fleischer ab, 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plaque psoriasis: a phase 3 randomised non-inferiority trial. lancet. 2015;386(9993):552-61. 33. valenzuela f, paul c, mallbris l, et al. tofacitinib versus etanercept or placebo in patients with moderate to severe chronic plaque psoriasis: patient-reported outcomes from a phase 3 study. j eur acad dermatol venereol. 2016;30(10):1753-1759. 34. strober be, crowley jj, yamauchi ps, olds m, williams da. efficacy and safety results from a phase iii, randomized controlled trial comparing the safety and efficacy of briakinumab with etanercept and placebo in patients with moderate to severe chronic plaque psoriasis. br j dermatol. 2011;165(3):661-8. 35. leonardi cl, powers jl, matheson rt, et al. etanercept as monotherapy in patients with psoriasis. n engl j med. 2003;349(21):2014-22. 36. gottlieb ab, matheson rt, lowe n, et al. a randomized trial of etanercept as monotherapy for psoriasis. arch dermatol. 2003;139(12):1627-32. 37. lowe n, lebsack m wande l. psoriasis patients show improved quality of life when treated with etanercept. ann dermatol venereol 2002; 129: 1s762. 38. krueger gg, langley rg, finlay ay, et al. patient-reported outcomes of psoriasis improvement with etanercept therapy: results of a randomized phase iii trial. br j dermatol. 2005;153(6):1192-9. 39. tyring s, gottlieb a, papp k, et al. etanercept and clinical outcomes, fatigue, and depression in psoriasis: double-blind placebo-controlled randomised phase iii trial. lancet. 2006;367(9504):29-35. 40. reich k, segaert s, van de kerkhof p, et al. once-weekly administration of etanercept 50 mg improves patientreported outcomes in patients with moderate-to-severe plaque psoriasis. dermatology (basel). 2009;219(3):239-49. 41. gottlieb ab, leonardi c, kerdel f, mehlis s, olds m, williams da. efficacy and safety of briakinumab vs. etanercept and placebo in patients with moderate to severe chronic plaque psoriasis. br j dermatol. 2011;165(3):652-60. 42. feldman sr, gordon kb, bala m, et al. infliximab treatment results in significant improvement in the quality of life of patients with severe psoriasis: a double-blind placebo-controlled trial. br j dermatol. 2005;152(5):954-60. 43. gottlieb ab, evans r, li s, et al. infliximab induction therapy for patients with severe plaque-type psoriasis: a randomized, double-blind, placebo-controlled trial. j am acad dermatol. 2004;51(4):534-42. 44. feldman sr, gottlieb ab, bala m, et al. infliximab improves health-related quality of life in the presence of comorbidities among patients with moderate-to-severe psoriasis. br j dermatol. 2008;159(3):704-10. 45. menter a, feldman sr, weinstein gd, et al. a randomized comparison of continuous vs. intermittent infliximab maintenance regimens over 1 year in the treatment of moderate-to-severe plaque psoriasis. j am acad dermatol. 2007;56(1):31.e1-15. 46. yang hz, wang k, jin hz, et al. infliximab monotherapy for chinese patients with moderate to severe plaque psoriasis: a randomized, double-blind, placebo-controlled skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 294 multicenter trial. chin med j. 2012;125(11):1845-51. 47. torii h, nakagawa h. infliximab monotherapy in japanese patients with moderate-to-severe plaque psoriasis and psoriatic arthritis. a randomized, double-blind, placebo-controlled multicenter trial. j dermatol sci. 2010;59(1):40-9. 48. reich k, nestle fo, papp k, et al. improvement in quality of life with infliximab induction and maintenance therapy in patients with moderate-tosevere psoriasis: a randomized controlled trial. br j dermatol. 2006;154(6):1161-8. 49. griffiths ce, reich k, lebwohl m, et al. comparison of ixekizumab with etanercept or placebo in moderate-tosevere psoriasis (uncover-2 and uncover-3): results from two phase 3 randomised trials. lancet. 2015;386(9993):541-51. 50. leonardi c, matheson r, zachariae c, et al. anti-interleukin-17 monoclonal antibody ixekizumab in chronic plaque psoriasis. n 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2016;74(5):ab273. 55. langley rg, elewski be, lebwohl m, et al. secukinumab in plaque psoriasis-results of two phase 3 trials. n engl j med. 2014;371(4):326-38. 56. paul c, lacour jp, tedremets l, et al. efficacy, safety and usability of secukinumab administration by autoinjector/pen in psoriasis: a randomized, controlled trial (juncture). j eur acad dermatol venereol. 2015;29(6):1082-90. 57. leonardi cl, kimball ab, papp ka, et al. efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 76-week results from a randomised, double-blind, placebocontrolled trial (phoenix 1). lancet. 2008;371(9625):1665-74. 58. papp ka, langley rg, lebwohl m, et al. efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (phoenix 2). lancet. 2008;371(9625):1675-84. 59. igarashi a, kato t, kato m, song m, nakagawa h. efficacy and safety of ustekinumab in japanese patients with moderate-to-severe plaque-type psoriasis: long-term results from a phase 2/3 clinical trial. j dermatol. 2012;39(3):242-52. skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 295 60. krueger gg, langley rg, leonardi c, et al. a human interleukin-12/23 monoclonal antibody for the treatment of psoriasis. n engl j med. 2007;356(6):580-92. 61. zhu x, zheng m, song m, et al. efficacy and safety of ustekinumab in chinese patients with moderate to severe plaque-type psoriasis: results from a phase 3 clinical trial (lotus). j drugs dermatol. 2013;12(2):166-74. 62. tsai tf, ho jc, song m, et al. efficacy and safety of ustekinumab for the treatment of moderate-to-severe psoriasis: a phase iii, randomized, placebo-controlled trial in taiwanese and korean patients (pearl). j dermatol sci. 2011;63(3):154-63. 63. papp ka, blauvelt a, bukhalo m, et al. selective blockade of il-23p19 with bi 655066 is associated with significant improvement in qol outcomes compared with ustekinumab in patients with moderate-to-severe plaque psoriasis. j am acad dermatol. 2016;74(5):ab275. skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 296 appendix 1. detailed search strategy. search conducted on september 8th, 2016: search conducted on august 30th, 2016: pubmed search category searc h query items found quality of life terms #1 quality of life 278,988 #2 dlqi 795 #3 dermatology life quality index 1,802 #4 dermatology quality of life index 1,802 #5 (#1 or #2 or #3 or #4) 279,007 drug terms #6 secukinumab 213 #7 adalimumab 5,323 #8 infliximab 11,143 #9 ixekizumab 102 #10 ustekinumab 828 #11 etanercept 6,676 #12 biologic therapy 516,999 #13 biologic 1,386,2 14 #14 (#6 or #7 or #8 or #9 or #10 or #11 or #12 or #13) 1,871,1 08 disease term #15 psoriasis 40,998 design terms #16 randomized controlled trials as topic [mesh major topic] 15,816 #17 "randomized controlled trials as topic" [mesh terms] 105,636 #18 random allocation [mesh terms] 87,192 #19 double blind method [mesh terms] 135,739 #20 "controlled clinical trial" [publication type] 503,881 #21 "randomized controlled trial" [publication 418,036 skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 297 type] #22 "clinical trials as topic" [mesh terms] 292,996 #23 "clinical trial" [publication type] 738,696 #24 (#16 or #17 or (#18 and (#19 or #22 or #23)) or #20 or #21) 607,554 #25 (((randomised and control and clinical and trial) or (randomized and control and clinical and trial))) 129,757 #26 ((((double or single or triple or treble) and (blind* or mask*) and (random*)))) 164,021 #27 (((random and allocat*) and control* and trial)) 22 #28 (#25 or #26 or #27) 258,498 #29 (#24 and #28) 231,144 language term #30 english [language] 21,827, 863 compilation of quality of life, drug terms, disease term, and design terms #31 (#5 and #14 and #15 and #29 and #30) 76 search conducted on august 25th, 2016: embase search category sear ch query hits design terms #1 "randomized controlled trial (topic)"/exp 102,487 #2 "randomized controlled trial"/exp 410,524 #3 "randomization"/exp 70,729 #4 "double blind procedure"/exp 130,636 #5 [controlled clinical trial]/lim 607,113 #6 [randomized controlled trial]/lim 510,524 #7 "clinical trial"/exp 1,105,349 #8 "clinical trial (topic)"/exp 200,673 #9 #1 or #2 or #3 or #4 or #5 or #6 783,138 #10 singl*:ab,ti or doubl*:ab,ti or treb*:ab,ti or tripl*:ab,ti and (blind*:ab,ti or mask*:ab,ti) 212,673 #11 "placebo"/exp 292,811 #12 random* and (clinical or control*) and trial or (placebo* and ("randomly 676,434 skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 298 allocated" or (allocated and random*))) #13 (#7 or #8) and (#10 or #11 or #12) 672,466 #14 #9 or #13 890,573 disease terms #15 ‘psoriasis’ 63,602 drug terms #16 ‘secukinumab’ 931 #17 ‘adalimumab’ 21,275 #18 ‘infliximab’ 37,012 #19 ‘ixekizumab’ 467 #20 ‘ustekinumab’ 3,014 #21 ‘etanercept’ 23,852 #22 ‘biologic therapy’ 3,346 #23 ‘biologic’ 76,906 #24 (#16 or #17 or #18 or #19 or #20 or #21 or #22 or #23) 123,128 quality of life terms #25 dlqi 1,709 #26 ‘dermatology life quality index’ 2,316 #27 ‘dermatology quality of life index’ 63 #28 ‘quality of life’ 386,267 #29 (#25 or #26 or #27 or #28) 386,734 language terms #30 [english]/lim 25,124,781 final (#14 and #15 and #24 and #29 and #30) 461 search conducted on august 25th, 2016: ovid/medline search categ ory sear ch query hits desig n terms #1 randomized controlled trials as topic/ 109,437 #2 randomized controlled trial/ 428,678 #3 random allocation/ 88,489 #4 double blind method/ 138,784 #5 controlled clinical trial.pt. 91,573 #6 randomized controlled trial.pt. 428,678 #7 clinical trial/ 504,873 #8 clinical trial.pt. 504,873 skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 299 #9 clinical trials as topic/ 179,085 #10 1 or 2 or 3 or 4 or 5 or 6 698,072 #11 7 or 8 or 9 613,026 #12 ((singl* or doubl* or treb* or tripl*) and (blind* or mask*)).ab,ti. 150,294 #13 placebos/ 33,637 #14 ((random* and (clinical or control*) and trial) or (placebo* and ("randomly allocated" or (allocated and random*)))).mp. [mp = title, abstract, original title, name of substance word, subject heading word, keyword heading word, protocol supplementary concept, rare disease supplementary concept, unique identifier] 501,456 #15 12 or 13 or 14 555,680 #16 11 and 15 259,650 #17 10 or 16 713,005 disea se terms #18 psoriasis/ 29,520 drug terms #19 secukinumab.mp. 134 #20 infliximab/ 8,053 #21 adalimumab/ 3,520 #22 ixekizumab.mp. 47 #23 ustekinumab/ 439 #24 etanercept/ 4,798 #25 biologic therapy/ 1,836 #26 biologic.mp. 48,461 #27 19 or 20 or 21 or 22 or 23 or 24 or 25 or 26 61,907 qualit y of life terms #28 dlqi.mp. 638 #29 dermatology life quality index.mp. 879 skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 300 #30 dermatology quality of life index.mp. 26 #31 quality of life/ 142,263 #32 28 or 29 or 30 or 31 142,443 final #33 17 and 18 and 27 and 32 99 cochrane library search categ ory sear ch query hits #1 psoriasis 4125 qualit y of life terms #2 dlqi 320 #3 dermatology life quality index 723 #4 dermatology quality of life index 723 #5 quality of life 58281 #6 #2 or #3 or #4 or #5 58286 drug terms #7 secukinumab 150 #8 infliximab 1371 #9 adalimumab 1106 #10 ixekizumab 27 #11 ustekinumab 196 #12 etanercept 1170 #13 biologic therapy 1322 #14 biologic 2011 #15 #7 or #8 or #9 or #10 or #11 or #12 or #13 or #14 4728 final #16 #1 and #6 and #15 234 skin september 2018 volume 2 issue 5 copyright 2018 the national society for cutaneous medicine 301 appendix 2. risk of bias table for the included studies. low risk high risk uncertain risk skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 418 brief articles pemphigus vulgaris following influenza: a case report kristen bice, md1, channing hood, bs,1 rawaa almukhtar, md1, michelle gerdes, md1, pamela martin, md1, brian lee, md1 1louisiana state university health sciences center, department of dermatology, children’s hospital, new orleans, la the association between viral infection and autoimmune disease is well-recognized in the literature.1,2,3 in the case of pemphigus vulgaris, members of the herpesviridae family, including hsv, cmv, vzv, ebv, and hhv-8, have long been implicated. there are several hypotheses as to how viruses can react against keratinocyte proteins and induce autoimmune acantholysis seen in pemphigus. the association between viruses may be causal, may be due to molecular mimicry of viral and host proteins, or may be due to exposure of previously hidden host proteins after virus-induced tissue damage.3 we report a 17-year-old male who presented with a case of mucosal-predominant pemphigus vulgaris temporally associated with influenza virus infection. the patient initially presented with fever and a sore throat for three days duration. he tested negative for strep throat, but positive for influenza via a rapid influenza diagnostic test. he was prescribed oseltamivir; however, he did not take this or any other medications to treat the influenza. over the next several weeks, he began to develop progressive oral ulcers until the entire oropharynx was involved with resultant poor oral intake and associated weight loss. he also developed waxing and waning conjunctival injection and ocular pain during this time. he denied any associated joint pains, genital ulcers, urinary changes, vision changes, or skin rash. there was no family history of autoimmune disease. he abstract viruses have long been implicated as potential triggers of autoimmune disease. in the case of pemphigus vulgaris, members of the herpesviridae family are often associated with its development. there have also been reports of pemphigus being triggered by the influenza vaccine. we report a case of a 17-year-old male who developed mucous membranepredominant pemphigus vulgaris after testing positive for the influenza virus and discuss proposed hypotheses for the association between viral infections and autoimmunity, such as molecular mimicry and epitope spreading. introduction case report skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 419 also denied taking any medications prior to or during this time. his symptoms progressed over a period of six weeks at which point he presented again to his primary care physician for further evaluation. the patient had a thorough yet unrevealing autoimmune and infectious workup (table 1). he was then sent for direct admission to the hospital for consultation of dermatology, gastroenterology, ophthalmology, and allergy and immunology. on physical exam he had extensive coalescent ulcerations and erosions along the buccal mucosa, soft palate, and posterior oropharynx. in addition, the patient had hemorrhagic, crusted ulcerations on his upper and lower lip (fig. 1). his conjunctivae were injected with no drainage or crusting. no intact vesicles or bullae were appreciated. there was no skin involvement noted. an infectious workup for cmv, hsv, and mycoplasma pneumoniae was negative. the patient underwent egd, which revealed extensive ulceration throughout the esophagus. biopsies of both the mucosal lip (fig. 2) and esophagus were obtained and revealed similar findings of full thickness and suprabasal acantholysis with maintenance of the attachment of the basal cell to the basement membrane, imparting a “tombstone” appearance. significant dyskeratosis and cytopathic viral effect were absent. the subepithelial region showed a mixed infiltrate of lymphoid cells and eosinophils. direct immunofluorescence taken from the lower lip showed weak deposits of igg1 and igg4 in the intercellular areas of the epithelium. serologic testing revealed an elevation in desmoglein 3 (table 1), consistent with pemphigus vulgaris with mucosal predominance. after the diagnosis was confirmed, we placed the patient on 125mg/day of iv methylprednisolone. he experienced gradual improvement in his ulcers, conjunctival injection, and oral intake over the next few days. he was transitioned to oral prednisone prior to hospital discharge. at outpatient follow-up, he was started on dapsone in addition to systemic steroids, however after several weeks he did not demonstrate adequate improvement and thus the dapsone was discontinued and he was placed on azathioprine. several attempts at tapering the steroid were made with worsening of disease. after an adequate trial of azathioprine, this medication was stopped, and he was started on mycophenolate mofetil, while still on highdose systemic steroids, with plans to initiate rituximab. figure 1. erosions and crusted ulcerations of the upper and lower mucosal lips. skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 420 figure 2. punch biopsy from the mucosal lip showing suprabasilar acantholysis without dyskeratosis, creating a “row of tombstones” appearance (hematoxylin-eosin stain). table 1. laboratory values from patient workup laboratory test result reference range esr 6 mm/hr 0-20 mm/hr crp <0.5 mg/dl 0.0-0.99 mg/dl ana negative - m. pneumoniae ab igg 0.90 u/l ≤ 0.09 u/l m. pneumoniae ab igm 0.03 u/l ≤ 0.76 u/l dfa for hsv negative for hsv - hsv pcr (oral swab) not detected - hsv pcr (left eye swab) not detected - hepatitis c antibody non-reactive - hepatitis b surface antibody non-reactive - hepatitis b surface antigen non-reactive - hepatitis b core antibody non-reactive - respiratory panel* negative - urine culture no growth 2 days - blood culture no growth 5 days - desmoglein 1 igg 5 u positive: >20 u borderline: 14-20 u negative: <14 u desmoglein 3 igg 210 u positive: >20 u borderline: 9-20 u negative: <9 u bullous pemphigoid antigen 180 kda igg 1 u positive: ≥ 9 u negative: < 9 u bullous pemphigoid antigen 230 kda igg 2 u positive: ≥ 9 u negative: < 9 u *tested by pcr for adenovirus, coronavirus 229e, coronavirus hku1, coronavirus nl63, coronavirus oc43, human metapneumovirus, human rhinovirus/enterovirus, influenza a, influenza a h1, influenza a h1-2009, influenza a h3, influenza b, parainfluenza 1,2,3,4, rsv, bordetella pertussis, chlamydophila pneumoniae, mycoplasma pneumoniae skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 421 the immunopathogenesis of pemphigus has not been well-described, but it is thought to develop from interactions between genetic and environmental factors. environmental factors described in the literature include stress, drugs, hormones, tumors, trauma, vaccinations, and of particular interest in this case, viral infections. it has been hypothesized that a virus can induce pemphigus in a number of different ways including through epitope spreading and molecular mimicry. in epitope spreading, an inflammatory process may cause tissue damage such that proteins that were once hidden become exposed to the immune system, leading to a secondary autoimmune response. during a viral infection, epitope spreading may occur when interferons lead to macrophagemediated tissue damage with subsequent exposure to keratinocyte proteins. this exposure then induces an autoimmune response that results in pemphigus.4,5 supporting this theory, interferon treatment has been shown to induce both pemphigus and other autoimmune bullous diseases.6,7,8 epitope spreading may also explain how patients with mucosal-predominant pemphigus go on to develop skin lesions. the desmoglein 3 autoantibodies may lead to tissue damage and an exposed secondary epitope, desmoglein 1. autoantibodies then develop to desmoglein 1 resulting in the blistering skin lesions seen in pemphigus.4 molecular mimicry is another possible mechanism through which viruses and pemphigus may be related. it occurs when viral fragments, processed by antigen presenting cells, closely resemble host proteins. this leads to the viral immune response cross-reacting with host tissues.3,5 given the high specificity of rapid influenza diagnostic tests (90%-95%)9 and thus low false-positive rate, we believe this was a true case of influenza preceding the onset of pemphigus vulgaris. there have been reports in the literature of pemphigus being induced by the influenza vaccine10,11 and a report of mucocutaneous pemphigus occurring after life-threatening h1n1 infection.12 taken together with the present case, we propose that influenza virus may be another potential viral trigger for pemphigus vulgaris. conflict of interest disclosures: none funding: none corresponding author: kristen bice, md louisiana state university health sciences center department of dermatology children’s hospital 1542 tulane ave. new orleans, la 70112 ste. 639, united states tel: (504) 568-7110 fax: (504) 568-2170 email: kbice@lsuhsc.edu references: 1. ahmed ar, rosen gb. viruses in pemphigus. int j dermatol. 1989;28(4):209-17. 2. brenner s, sasson a, sharon o. pemphigus and infections. clin dermatol. 2002;20(2):114-8. 3. ruocco e, ruocco v, lo schiavo a, brunetti g, wolf r. viruses and pemphigus. an intriguing never-ending story. dermatology. 2014;229(4):310-5. 4. chan ls, vanderlugt cj, hashimoto t, nishikawa t, zone jj, black mm, et al. epitope spreading. lessons from autoimmune skin disease. j invest dermatol. 1998;110(2):103-9. discussion mailto:kbice@lsuhsc.edu skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 422 5. tchernev g, orfanos ce. antigen mimicry, epitope spreading and the pathogenesis of pemphigus. tissue antigens. 2006 oct;68(4):2806. 6. ramseur wl, richards f ii, duggan db: a case of fatal pemphigus vulgaris in association with beta interferon and interleukin-2 therapy. cancer. 1989;63(10):2005–7. 7. kirsner rs, anhalt gj, kerdel fa. treatment with alpha interferon associated with the development of paraneoplastic pemphigus. br j dermatol. 1995;132(3):474–478. 8. parodi a, semino m, gallo r, rebora a. bullous eruption with circulating pemphigus-like antibodies following interferon-alpha therapy. dermatology. 1993;186(2):155–7. 9. centers for disease control and prevention. rapid diagnostic testing for influenza: information for clinical laboratory directors. march 6, 2018; available from: https://www.cdc.gov/flu/professionals/diagnosis/r apidlab.htm. 10. mignogna md, lo muzio l, ruocco e. pemphigus induction by influenza vaccination. int j dermatol. 2000;39(10):800. 11. giles ja, orozco sh, nava la, hernandez vj. pemphigus vulgaris induced by seasonal antiinfluenza vaccine. dermatologia revista mexicana. 2012;56(5):323-326. 12. sinha p, chatterjee m, vasudevan b. pemphigus vulgaris: a dermatological sequel of severe h1n1 infection. indian dermatol online j. 2014;5(2):216-217. skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 157 rising derm stars® atypical intraepidermal melanocytic proliferation – but now what? shira wieder, md, matthew goldberg, md, rajendra singh, md 1department of dermatology, icahn school of medicine at mount sinai, new york, ny background/objectives: atypical intraepidermal melanocytic proliferation (aimp) is a descriptive histopathologic term that has alternative meanings at different institutions. it can include atypical lentigines or evolving/early dysplastic junctional nevi as well as melanoma in situ (mis) but whose features are insufficient for a diagnosis of melanoma.1 this leads to inconsistent management recommendations. our surveys of expert dermatopathologists about how these types of lesions are handled at other institutions yielded extensive variability in the definition of aimp. this underscores the urgent need to better understand this entity. methods: in this retrospective study, a cohort of aimp cases was selected. all cases were limited to the year 2008 so that longer follow up data could be collected. results: a total of 529 cases were evaluated, 312 met inclusion criteria. females outnumbered males 2:1. the majority of aimp’s were located on areas of the body with intermittent sun exposure (back, lower legs, arms, chest). the differential diagnosis listed by the clinician was “atypical junctional nevus” (or variants that included the words “atypical” or “dysplastic”) in 70.0% of cases followed by “melanoma” in only 7.9% of cases (figure 1). of the 312 cases of aimp, 5 (1.6%) were found to be melanoma on re-excision. of these, 4 (80%) were on maximally sunexposed areas (face/scalp or ears). for the differential diagnosis, clinicians included “melanoma” in 3/5 of the cases (60%). for all 319 patients, all subsequent biopsies performed between 2008 to 2017 were looked at to see if any had occurred in the same location as the previous aimp’s. 2/312 (0.64%) of cases had the same location identified as the site of the previous aimp’s suggestive of progression to melanoma. in addition, 14 cases that were determined to be aimp at the author’s institution were scanned using whole slide imaging (wsi) and an online digital slide platform. they were sent to expert dermatopathologists across the united states and internationally. each dermatopathologist read the cases as they would at their own institution. these results were divided into 3 categories: benign, uncertain and malignant (figure 2). the discrepancy between the dermatopathologists was astounding and demonstrated the value of this research. conclusion: in conclusion, aimp is a poorly researched entity and when used in practice, has significant impact on patient care. one of the most significant suggestions made by the data is that aimp found on sun-exposed areas may warrant re-consideration as a lentigo maligna. another important skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 158 implication made by this data is that few aimp’s progress over time to become melanoma. this has important implications for patients and their care. figure 1. the differential diagnoses included by clinicians with the biopsies of lesions that were read as atypical intraepidermal melanocytic proliferation by dermatopahtologist’s at the author’s institution. figure 2. 14 cases of aimp were sent as whole slide digital images to expert dermatopathologists across the united states and internationally. the diversity of opinion is displayed below. references: 1. zhang, junqian, et al. “diagnostic change from atypical intraepidermal melanocytic proliferation to melanoma after conventional excision: a single academic institution cross-sectional study.” dermatologic surgery, vol. 42, no. 10, 2016, pp. 1147–1154 0% 20% 40% 60% 80% 100% unknown malignant uncertain benign microsoft word 9. 615 proof done.docx skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 64 brief articles verrucous keratoses associated with checkpoint inhibitor immunotherapy joshua l. owen, md, phd,1* cory kosche, bs,1* jennifer n. choi, md1,2 1department of dermatology, northwestern university, feinberg school of medicine, chicago, il 2robert h. lurie comprehensive cancer center, northwestern university, feinberg school of medicine, chicago, il *these authors contributed equally to this work. immune checkpoints act as a normal brake on immune activation and response. cytotoxic t lymphocyte associated antigen 4 (ctla-4) regulates the activation of naïve t cells.1 in contrast, programmed cell death protein 1 (pd-1), expressed on t cells, b cells, nk cells, and macrophages, binds to programmed death-ligand 1 and 2 (pd-l1, pd-l2) leading to downregulation of the adaptive immune response.1 many cancers have been shown to co-opt these immune checkpoints to evade detection and destruction by the immune system.2 immune checkpoint inhibitors have been developed to block this downregulation of the immune response, facilitating an immunologic response to cancers.1 the first approved checkpoint inhibitor, ipilimumab, is a humanized anti-ctla-4 immunoglobulin monoclonal antibody (mab).1 nivolumab is a fully human anti-pd-1 immunoglobulin g4 (igg4) mab, whereas pembrolizumab is a humanized anti-pd-1 igg4 mab.1 increasing clinical use of checkpoint inhibitors has led to the recognition of immune-related adverse events (iraes).1 the most common iraes include skin eruptions and itch, fatigue, diarrhea, and endocrinopathies.1 the skin eruptions include maculopapular, papulopustular, lichenoid dermatitis, vitiligo, bullous disorders, and eruptive keratoacanthomas.3,4 here we present, to our knowledge, the first introduction introduction: checkpoint inhibitor immunotherapy is associated with numerous adverse events, including eruptive keratoacanthomas and squamous cell carcinomas. however, no cases of immunotherapy-associated verrucous keratoses (vks) have been reported. vks are proliferative lesions generally considered benign, although they have been suggested to represent premalignant lesions. cases: we present the first case series of three patients with immunotherapy-associated vks. the patients were receiving nivolumab for renal cell carcinoma, combination ipilimumab/nivolumab for non-small cell lung carcinoma, and pembrolizumab for malignant melanoma. the vks appeared 3-7 months after initiation of immunotherapy. lesions were treated with shave removal or cryosurgery without recurrence. this report adds to the spectrum of cutaneous squamoproliferative lesions induced by checkpoint inhibitor immunotherapy. abstract skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 65 reported cases of verrucous keratoses (vks) associated with checkpoint inhibitor immunotherapy. case 1. an 87-year-old man with a history of psoriasis, prostate cancer (diagnosed 17 years earlier), metastatic clear cell renal carcinoma (initial diagnosis 13 years prior, metastasis found 5 years ago), and infiltrating ductal breast carcinoma (diagnosed 1 year ago) presented with a 2-month history of a non-pruritic eruption over the upper body. the patient had begun treatment with nivolumab after failing pazopanib for his metastatic renal cell carcinoma. after receiving 6 cycles over 3 months, nivolumab was discontinued due to the development of profound arthralgias as well as flares of psoriasis. treatment with topical corticosteroids and vitamin d analogues was unsuccessful, leading to initiation of narrowband uvb phototherapy. despite nivolumab being held for 4 months, his metastatic renal tumors continued to regress, demonstrating an ongoing immunologic response to the malignancy. seven months after initiating nivolumab, physical exam revealed several discrete erythematous papules and plaques diffusely over the upper and lower extremities and trunk (figure 1a). dermoscopy of the lesions showed exophytic hyperkeratotic papules with central white keratin horns containing thrombosed vessels and an erythematous halo peripherally (figure 1b). biopsies were performed on four representative lesions which showed marked hyperkeratosis and acanthosis, and a dermal lymphohistiocytic infiltrate; koilocytosis and features of invasive growth were absent. overall, biopsies were consistent with an inflamed vk (figure 2). the lesions did not recur after the shave removals were performed, and other smaller similar papules resolved with cryosurgery. case 2. a 71-year-old woman with a history of metastatic large cell neuroendocrine lung carcinoma initiated treatment with combination ipilimumab and nivolumab after previous treatments with carboplatin, etoposide, and pemetrexed. five months after beginning immunotherapy, she presented with a growth on the medial cheek. it had been enlarging over the last two weeks, with intermittent pruritus and bleeding. physical exam demonstrated a 2-cm fusiform, stuck-on plaque with yellow and heme crust and surrounding erythema. biopsy of the lesion demonstrated an inflamed vk without atypical cells. case 3. a 59-year-old woman with a history of stage iiib melanoma undergoing initial treatment with pembrolizumab presented with a one-week history of a sudden growth on her chest three months after initiating immunotherapy. physical exam demonstrated a 6-mm inflamed, stuck-on papule with hemorrhagic crust and surrounding erythema. biopsy of the lesion demonstrated an inflamed vk. vks are squamoproliferative lesions that lie on a spectrum of epithelial hyperplasia. though generally benign, there are concerns that vks may represent premalignant lesions if new in onset in the context of anticancer therapy.5 studies of braf inhibitors (e.g., vemurafenib and dabrafenib) in the treatment of melanoma have documented the development of verrucae vulgaris, verrucous keratoses, actinic keratoses, kas, and squamous cell carcinomas (sccs) in up to 79% of patients.6 the mechanism for this is report of cases discussion skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 66 figure 1. (1a) clinical image demonstrating numerous discrete erythematous verrucous papules on the back. (1b) dermoscopic image demonstrating an exophytic hyperkeratotic papule with central white keratin horns containing thrombosed vessels and an erythematous halo peripherally. (1a) (1b) figure 2. histopathologic image demonstrating marked hyperkeratosis and acanthosis, and a dermal lymphohistiocytic infiltrate. koilocytosis and invasive growth are absent (hematoxylin and eosin stain, 40x original magnification). thought to occur via paradoxical activation of the mitogen-activated protein kinase (mapk) pathway in cells which do not harbor the v600e braf mutation, leading to proliferation and tumorigenic growth of keratinocytes.7 this would be, to our knowledge, the first report of immunotherapy-induced vks. previous reports have documented the occurrence of eruptive kas and eruptive sccs during immunotherapy. 4,8-10 therefore checkpoint inhibitor immunotherapy may serve to exaggerate a squamoproliferative pathway in some patients, leading to the development of eruptive vks, kas, or sccs. we cannot completely rule out the possibility of pre-existing or incipient verrucous or seborrheic keratoses (sks) that subsequently enlarged and became inflamed with immunotherapy. it is also possible that the lesions represented a precursor to a developing ka or scc-like growth that have previously been reported, although we believe this is less likely given their clinical skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 67 and benign histopathological appearance. patient 1 had a more diffuse, multi-lesional presentation which might argue for a broad inflammatory response to preexisting keratoses. however, patients 2 and 3 each presented with one inflamed vk at sites that were clearly documented with recent photos as having no previous sk or other lesion at the site. each vk biopsied demonstrated a lymphohistiocytic dermal infiltrate, similar to previous reports of immunotherapy induced kas.4,8-9 whether this represents a nonspecific inflammatory response or a targeted immune response remains an open question. while the pathophysiology of immunotherapy-induced vks is unknown, an intriguing observation seen in patient 1 was a continued development of vks and reduction in tumor burden despite cessation of anti-pd-1 therapy. the persistent immunological response despite discontinuing anti-pd-1 therapy is a hallmark of immune checkpoint inhibition.1 anti-pd-1 therapy is now approved for the treatment of advanced cutaneous squamous cell carcinoma.11 it will be important to surveil these patients for the development of new keratinizing skin lesions, which may cloud the clinical picture. clinicians should be aware of the possible development of any kind of new cutaneous squamoproliferative lesion, both benign and atypical, in the context of immunotherapy that are unrelated to the primary cancer. conflict of interest disclosures: none funding: none corresponding author: jennifer n. choi, md 676 n. st. clair st. suite 1600 chicago, il 60611 phone: (312) 695-8106 fax: (312) 503-5900 email: jennifer.choi@northwestern.edu references: 1. boutros c, tarhini a, routier e, et al. safety profiles of anti-ctla-4 and anti-pd-1 antibodies alone and in combination. nature reviews clinical oncology. 2016;13:473. 2. topalian sl, hodi fs, brahmer jr, et al. safety, activity, and immune correlates of anti–pd-1 antibody in cancer. new england journal of medicine. 2012;366(26):2443-2454. 3. naidoo j, page db, li bt, et al. toxicities of the anti-pd-1 and anti-pd-l1 immune checkpoint antibodies. annals of oncology : official journal of the european society for medical oncology. 2015;26(12):2375-2391. 4. freites-martinez a, kwong by, rieger ke, coit dg, colevas ad, lacouture me. eruptive keratoacanthomas associated with pembrolizumab therapy. jama dermatology. 2017. 5. anforth rm, blumetti tc, kefford rf, et al. cutaneous manifestations of dabrafenib (gsk2118436): a selective inhibitor of mutant braf in patients with metastatic melanoma. the british journal of dermatology. 2012;167(5):11531160. 6. de golian e, kwong by, swetter sm, pugliese sb. cutaneous complications of targeted melanoma therapy. current treatment options in oncology. 2016;17(11):57. 7. harvey nt, millward m, wood ba. squamoproliferative lesions arising in the setting of braf inhibition. the american journal of dermatopathology. 2012;34(8):822-826. 8. feldstein si, patel f, larsen l, kim e, hwang s, fung ma. eruptive keratoacanthomas arising in the setting of lichenoid toxicity after programmed cell death 1 inhibition with nivolumab. 2018;32(2):e58-e59. 9. bandino jp, elston dm. response to ‘eruptive keratoacanthomas arising in the setting of lichenoid toxicity after patients on antiprogrammed cell death-1 inhibition with nivolumab’. journal of the european academy of dermatology and venereology. 2018;32(2):e61-e62. 10. lee j, guffey dj, noland m-mb, russell ma. eruptive squamous cell carcinomas associated with programmed cell death protein-1 inhibitor therapy. indian journal of dermatology, venereology, and leprology. 2019;85(1):97. 11. migden mr, rischin d, schmults cd, et al. pd-1 blockade with cemiplimab in advanced cutaneous squamous-cell carcinoma. new england journal of medicine. 2018;379(4):341351. skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 108 resident competition research article associations of cutaneous immune-related adverse effects of immunotherapy with treatment response in patients with metastatic melanoma anagha bangalore kumar, mbbs1, alan h. bryce, md2, prakash vishnu, mbbs3, svetomir n. markovic, md, phd1, marian t. mcevoy, md4 1division of medical oncology mayo clinic, rochester, mn 2division of hematology and medical oncology, mayo clinic hospital, phoenix, az 3division of hematology and medical oncology, mayo clinic, jacksonville, fl 4department of dermatology, mayo clinic, rochester, mn immune checkpoint inhibitors (icis), such as ipilimumab (i), pembrolizumab (p), and nivolumab (n), have drastically improved the survival of patients with melanoma. although these immunotherapeutic agents act by harnessing the immune response to fight melanoma, they are also associated with unique immune-related adverse effects (iraes). regardless of the precise mechanism involved, all iraes occur because of excessive immune activation. abstract background: dermatologic toxicity is the most common immune-related adverse effect of cancer immunotherapy. methods: we retrospectively reviewed the health records of adult (≥18 years) melanoma patients who received ipilimumab, nivolumab, or pembrolizumab from january 1, 2011, through september 15, 2017, at mayo clinic. the χ2 test was used to assess the association between development of a cutaneous immune-related adverse effect and antitumoral response to the immune checkpoint inhibitors. odds ratios were calculated with logistic regression models and were adjusted for sex and immunotherapeutic drugs. we described the various cutaneous immune-related adverse effects and assessed the response to immunotherapy (each patient’s objective clinical response was categorized as favorable [complete or partial response] or unfavorable). we then determined whether development of a cutaneous immune-related adverse effect was associated with the clinical response. results: of 690 melanoma patients, 232 (33.6%) had a cutaneous immune-related adverse effect. the most common effects were dermatitis (21.4%), pruritus (5.5%), and vitiligo (4.2%). median (range) time to onset of dermatitis was 3 (0-7) weeks; lichenoid dermatitis, 12 (6-18) weeks; and vitiligo, 40 (12-96) weeks. development of a cutaneous immune-related adverse effect was significantly associated with favorable clinical response. conclusions: development of cutaneous immune-related adverse effects is associated with favorable responses to nivolumab, ipilimumab, pembrolizumab, and ipilimumab plus nivolumab therapy in patients with metastatic melanoma. introduction skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 109 any organ can be affected, but cutaneous iraes are the most common toxicities of icis.1 previous clinical trials and studies have reported incidence rates of 30% to 40% for cutaneous iraes associated with i, p, and n.1-3 studies have also shown that development of vitiligo is associated with better treatment response and prognosis of melanoma.4,5 however, sparse data describe the various cutaneous iraes and their associations with immunotherapy in a large cohort of patients with melanoma. we sought to describe the various cutaneous iraes, associations between these iraes and i, n, and p, and associations between skin reaction and antitumoral response to immunotherapy in melanoma patients. this study was approved by the mayo clinic institutional review board, and informed consent was waived for this retrospective study. we conducted a retrospective review of electronic health records of adult (age ≥18 years) melanoma patients who received ici therapy with i, n, or p from january 1, 2011, through september 15, 2017, at mayo clinic in rochester, minnesota; phoenix, arizona; and jacksonville, florida. patients were categorized into 2 groups: those who had a cutaneous irae and those who did not. cutaneous iraes were graded according to the common terminology criteria for adverse events version 4.03.6 to assess response to immunotherapy, we graded each patient’s objective clinical response as favorable (ie, complete or partial response) or unfavorable. for those who did not have a cutaneous irae while receiving any ici, the best response achieved while receiving immunotherapy was recorded. we excluded patients who had a concomitant second tumor (n=5); received chemotherapy and immunotherapy (n=8); received follow-up at other facilities, and therefore their responses could not be determined (n=7); and stopped ici because of intolerance (n=6). we used the χ2 test to assess the association between development of a cutaneous irae and antitumoral clinical response to ici therapy. odds ratios (ors) and 95% cis were calculated with logistic regression models and were adjusted for sex and immunotherapeutic drugs. p<.05 was considered significant. demographic characteristics we identified 690 melanoma patients (486 men and 204 women) who received i (n=228), n (n=16), p (n=297), or i+n combination therapy (n=149). of these, 232 patients (33.6%) reported a skin reaction to immunotherapy. the median (range) age of the patient cohort was 66 (26-93) years, and the median (range) age at diagnosis of melanoma was 61 (24-91) years. among those who had a cutaneous irae, 155 (66.8%) were men and 77 (33.2%) were women. the most common cutaneous irae was grade 1 dermatitis (103 patients [14.9%]), and other patients had vitiligo (29 [4.2%]), lichenoid dermatitis (7 [1.0%]), flare of preexisting psoriasis (7 [0.7%]), sclerodermoid reaction (2 [0.3%]), tumoral melanosis (2 [0.3%]), and bullous pemphigoid (1 [0.1%]) (table 1). duration, management, and outcome of the cutaneous iraes are summarized in table 2. after treatment initiation, the median (range) methods results skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 110 table 1. cutaneous immune-related adverse effects due to i, p, and n in melanoma patients (n=690) diagnosis no. of patients (%) grade (no. of patients) time to onset, median (range) site (no. of patients) any cutaneous condition 232 (33.6) not determined 3-40 wk self-reported maculopapular rash (24) dermatitis 148 (21.4) grade 1 (103) grade 2 (31) grade 3 (14) 3 (0-7) wk generalized (14), torso (71), extremities (59), and face and neck (4) maculopapular rash 145 (21.0) acneiform rash 1 (0.1) urticarial plaques 2 (0.3) pruritus without dermatitis 38 (5.5) grade 1 (32) grade 2 (4) grade 3 (2) 4 (0-12) wk generalized (21), torso (10), extremities (4), and face (3) vitiligo 29 (4.2) grade 1 (26) grade 2 (3) 40 (12-96) wka extremities (13), torso (10), face (2), and generalized (4) lichenoid dermatitisb 7 (1.0) grade 2 (7) 12 (6-18) wk extremities and torso (4), torso (2), and extremities (1) worsening psoriasis 5 (0.7) not graded 18 (9-30) wk extremities (3) and chest (2) sclerodermoid reactionb 2 (0.3) grade 2 (2) 15 and 39 wk extremities (2) tumoral melanosis 2 (0.3) not determined 40 and 56 wkc chest (1) and chest and back (1) bullous pemphigoid 1 (0.1) grade 2 (1) 36 wk extremities (1) abbreviations: i – ipilimumab; n – nivolumab; p – pembrolizumab. a eighteen patients had vitiligo while receiving p at a median (range) of 9 (2.5-23) months after treatment initiation; 1 patient, while receiving p (the exact time could not be determined); 4 patients, while receiving i at a median (range) of 4 (3-10) months; 3 patients, while receiving i+n combination therapy at a median (range) of 11 (4-11) months; 1 patient, at 9 months after starting p and 6 months after starting i; 1 patient, 17 months after the first dose of p and 6 months after starting i+n combination therapy; and 1 patient, while receiving n (the exact time could not be determined). b all cases were attributed to p. c one patient had 4 cycles of i+n combination therapy and later continued only n for 23 more cycles before melanosis was noted on the chest and back (14 months after the first cycle of n); the other patient had 4 cycles of i+n combination therapy and later continued only n for 24 more cycles before melanosis was noted on the chest (10 months after the first cycle of n). skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 111 table 2. duration, management, and outcome of cutaneous iraes cutaneous irae (no. of patients) duration (no. of patients) management (no. of patients) outcome (no. of patients) dermatitis (148) maculopapular rash (145; 24 with self-reported) urticarial plaque (2) acneiform rash (1) <1 wk (20) 1-2 wk (53) 2-4 wk (50) >4 wk (25) grade 1 and grade 2 were managed with topical corticosteroids, oral antihistamines (23), and rarely oral corticosteroids (26); grade 3 was managed with higher doses of corticosteroids and referral to a dermatologist responded to treatment (105) cleared on its own or with over-thecounter medication (35) required ici interruption (7) persisted at last follow-up (2) pruritus without dermatitis (38) <1 wk (6) 1-2 wk (6) 2-4 wk (21) >4 wk (5) topical corticosteroids (38) antihistamines (15) systemic corticosteroids (8) required ici interruption (1) vitiligo (29) persisted at the time of last follow-up sun protection (29) persisted at the last follow-up (29) lichenoid dermatitis (7) 2-4 wk (2) >4 wk (3) topical corticosteroids (7) oral corticosteroids (3) responded well to treatment (7) required ici interruption (1) worsening psoriasis (5) >4 wk (5) topical corticosteroids (5) apremilast (2) acitretin (1) responded to treatment (5) required ici interruption (3a) sclerodermoid changes (2) >4 wk (2) intravenous immunoglobulin, mycophenolate mofetil, and oral corticosteroids (1) hydroxychloroquine and oral corticosteroids (1) required ici interruption (2a) tumoral melanosis (2) persisted at last follow-up no treatment (2) persisted at last follow-up (2) bullous pemphigoid (1) >4 wk (1) oral corticosteroids, mycophenolate mofetil, doxycycline, and topical corticosteroids (1) responded to treatment and required ici interruption (1) abbreviations: ici – immune checkpoint inhibitor; irae – immune-related adverse effect. a one of these patients required permanent discontinuation of all icis. skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 112 time to onset of dermatitis was 3 (0-7) weeks; lichenoid dermatitis, 12 (6-18) weeks; and vitiligo, 40 (12-96) weeks. histopathologic characteristics biopsy was not performed for all cutaneous iraes. of 14 patients who underwent skin biopsy for evaluation of dermatitis, 7 had characteristics of lichenoid dermatitis, such as vacuolar interface dermatitis with scattered dyskeratotic keratinocytes and mixed perivascular inflammation. the other 7 showed characteristics of subacute dermatitis. results of skin biopsies confirmed the diagnoses of bullous pemphigoid, sclerodermoid reaction, lichenoid dermatitis, and tumoral melanosis. management most cutaneous iraes were managed by medical oncologists and treated with topical corticosteroids, with or without antihistamines. thirty-two patients (13.8%) were referred to dermatologists. severe cutaneous toxicity warranted hospitalization for further evaluation and aggressive management by dermatologists, in addition to permanent discontinuation of ici therapy. although ici treatment was interrupted in 15 patients, at the last follow-up, only 2 patients required permanent discontinuation of all icis. management strategies were based on the clinical judgment of the treating physicians and the symptoms and clinical signs at presentation. sex did not influence the likelihood of development of a cutaneous reaction (p=.94, determined with the χ2 test). patients receiving i+n combination therapy were more likely to have dermatitis than those receiving p (or [95% ci], 2.5 [1.24.8]; p=.01) or n alone (or [95% ci], 4.6 [1.0-19.9]; p=.04). development of a cutaneous irae was significantly associated with favorable clinical response (p<.001). the objective response rate (orr) of patients with a cutaneous irae was markedly greater than that of those who did not have a cutaneous irae (67.7% vs 37.2%) (table 3). the orr of those with a self-reported rash was 54.5%, and that of patients with vitiligo was 86.2%. patients who had vitiligo were more likely to have a favorable response than patients without vitiligo (or, 7.23). table 3. antitumor responses in patients with and without cutaneous iraes (n=664a) response patients without cutaneous iraes, no. (%) patients with cutaneous iraes, no. (%) favorableb 178 (37.2) 126 (67.7) unfavorable 300 (62.8) 60 (32.3) abbreviation: irae – immune-related adverse effect. a we initially identified 690 melanoma patients who received immune checkpoint inhibitors, but to assess treatment response we excluded patients who had a concomitant second tumor (n=5), received chemotherapy and immunotherapy (n=8), received follow-up at other facilities and therefore had responses that could not be determined (n=7), or stopped immune checkpoint inhibitors because of intolerance (n=6). b defined as a complete or partial response. incidence approximately one-third of our patients receiving i, n, p, or i+n combination therapy had a cutaneous irae. dermatitis (21.4%), pruritus without a rash (5.5%), and vitiligo (4.2%) were most commonly associated with these agents. the most common irae described in the health records was maculopapular rash; however, acneiform rashes and urticarial plaques were also seen. a recent meta-analysis of dermatologic toxicity due to icis reported a 16.7% incidence of all-grade dermatitis in patients receiving p and a 14.3% incidence in those receiving n.7 similar to the results of our study, low-grade dermatitis, pruritus, and discussion skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 113 vitiligo were the most common toxicities in their cohort. another meta-analysis reported a 24.3% incidence of dermatitis in patients receiving i.8 the likelihood of dermatitis is increased in patients receiving i+n combination therapy. in the current study, patients receiving i+n combination therapy were more likely to have dermatitis than those receiving p (or, 2.5) or n alone (or, 4.6). hwang9 compared cutaneous toxicities in melanoma patients receiving p alone with those of patients receiving p+i combination immunotherapy. in the latter group, the incidence of cutaneous irae was greater (88%) and the time to onset of these adverse effects was shorter. reports of individual cases and case series describe associations between i, p, and n and a wide range of cutaneous iraes,10,11 including xerosis,2,12-15 stomatitis,16 urticaria,16,17 photosensitivity reactions,12 hyperhidrosis,12 exfoliation,16 alopecia2,12,17 and hair color changes,2 psoriasis,18-20 bullous pemphigoid,21,22 lichenoid eruptions,23 lupus-like reaction,24 sclerodermoid reaction,25 panniculitis,26 erythema nodosum,27 and tumoral melanosis.28,29 studies have also reported generalized eruptions,30-33 including drug reaction with eosinophilia and systemic symptom syndrome,34 sarcoidosis-like rash,35 lichen nitidus,36 amyloidosis,37 sweet syndrome,38 acute generalized exanthematous pustulosis,39 and vasculitis.40 nevertheless, a particular cutaneous irae cannot be definitively assigned to a drug on the basis of a single case report. onset and management of cutaneous iraes the current practice in medical oncology for the management of dermatitis is based on extent of cutaneous eruption and symptoms.41 for patients with less than 20% body surface area (bsa) involvement, symptomatic treatment includes topical corticosteroids (triamcinolone 0.1% to torso and limbs, or hydrocortisone 1% or 2.5% to face and flexures) and oral antihistamines; 20% to 50% bsa, oral corticosteroids (eg, prednisolone, 0.5-1 mg/kg), topical therapy (similar to that used to treat <20% bsa), and possible consultation with a dermatologist; more than 50% bsa, oral corticosteroids (eg, prednisolone, 1-2 mg/kg) and referral to a dermatologist. interestingly, we noted that some cutaneous iraes occurred acutely but some, such as vitiligo, bullous pemphigoid, and sclerodermoid reaction, occurred later in the course of treatment (ie, median time to onset ranged from 3 to 40 weeks). a recent study of 17 patients showed similar times to onset of lichenoid dermatitis and bullous pemphigoid as seen in our cohort.42 many of our patients had grade 1 dermatitis that lasted from 1 to 2 weeks and were treated with topical corticosteroids, consistent with previous reports. most iraes resolve within weeks to months after initiation of immunosuppressive therapy.3 our management strategies were in line with the recently published guidelines by the american society of clinical oncology.43 these guidelines will serve as a treatment model until prospective clinical data are available. histopathologic characteristics the most common biopsy findings of maculopapular dermatitis include superficial perivascular lymphocytic dermatitis with eosinophils.44,45 patterns resembling granulomatous, lichenoid, and spongiotic dermatitis are not uncommon.44 the inflammatory infiltrate mostly consists of t lymphocytes with a predominance of cd4+ cells over cd8+ cells.44 tanaka et al46 reported an increase in interleukin 6 but not skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 114 tumor necrosis factor α in their series of 6 patients with metastatic melanoma who had n-induced psoriasis. although previous reports have identified immune infiltrates in skin biopsy specimens from patients with iraes,47 the specific antigens causing cutaneous iraes have not been identified. the association of development of vitiligo with favorable antitumoral response has been linked to epitope spreading, in which immune activity against a tumor-specific antigen extends to an antigen shared by the tumor and noncancerous melanocytes.47 association of cutaneous iraes with response lo et al47 reviewed the association of the development of cutaneous iraes with cancer prognosis and highlighted the significant association of vitiligo with favorable response to therapy; however, data on nonvitiligo cutaneous iraes were insufficient. sanlorenzo et al48 reported better cancer outcomes in patients who had a cutaneous irae due to p. they analyzed data of 83 patients with various cancers who were treated with p and reported that 42% of patients had cutaneous iraes. also, among patients who received p, those with a cutaneous irae had longer progression-free survival than those without a cutaneous irae. in our cohort, the orr of patients with a cutaneous irae was markedly greater than that of those who did not. twenty-nine (4.2%) patients had vitiligo, and the orr of these patients was 86.2% (25 of 29 patients). patients with vitiligo were more likely to have a favorable antitumoral response than patients without vitiligo (or, 7.23). previous studies have reported a survival benefit in melanoma patients who had vitiligo attributable to immunotherapy. in a study by hua et al,4 the orr was 71% for 17 patients who had vitiligo. a large metaanalysis reported that melanoma patients who had vitiligo (n=304) while receiving immunotherapy had better progression-free survival and overall survival than patients without vitiligo.5 the influence of lead-time bias should be considered in analyses of the association of cutaneous iraes with favorable response to immunotherapy because patients who respond well may receive the drug for a longer duration and may have more time for long-term cutaneous iraes to develop. limitations this retrospective study was prone to ascertainment bias. although our overall cohort was large, not all patients were evaluated by a dermatologist; most patients with cutaneous iraes were successfully treated by oncologists. the cohort also included patients with self-reported, shortterm skin eruptions. the precise time lines of the occurrence, treatment, and outcome of the cutaneous iraes were compiled on the basis of the clinical notes obtained with chart review. it was also challenging to classify and to ascertain the severity of each cutaneous irae with the common terminology criteria for adverse events grades. objective response rate was reported instead of overall survival or progression free survival. the cutaneous iraes associated with immunotherapy can have diverse presentations, and physicians must understand how to recognize and to manage these various iraes. prospective studies would help determine the precise time to onset, course, and management of cutaneous iraes. emerging evidence suggests that patients with a cutaneous irae may have a favorable response to conclusion skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 115 immunotherapy, and further research is required to evaluate this association. abbreviations: bsa – body surface area i – ipilimumab ici – immune checkpoint inhibitor irae – immune-related adverse effect n – nivolumab or – odds ratio orr – objective response rate p – pembrolizumab author contributions: dr. bangalore kumar, dr. mcevoy had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. study concept and design: dr. mcevoy, dr. markovic, dr. bryce, dr. vishnu. analysis and interpretation of data: dr. bangalore kumar, dr. mcevoy, dr. markovic. drafting of the manuscript: dr. bangalore kumar, dr. vishnu., dr. bryce, dr. markovic, dr. mcevoy. critical revision of the manuscript for important intellectual content: dr. bangalore kumar, dr. vishnu, dr. bryce, dr. markovic, dr. mcevoy. statistical analysis: all authors, mr paul novotny (statistician) from ccats conflict of interest disclosures: none funding: this study was supported by grant number ul1tr002377 from the national center for advancing translational sciences (ncats). its contents are solely the responsibility of the authors and do not necessarily represent the official views of the national institutes of health. a.b.k. was supported by grant number t32 gm008685-20 from the national institutes of health. the contents of this article are solely the responsibility of the authors and do not necessarily represent the official view of the national institutes of health. corresponding author: marian t. mcevoy, md department of dermatology mayo clinic, 200 first st sw rochester, mn 55905 email: mcevoy.marian@mayo.edu references: 1. naidoo j, page db, li bt, et al. toxicities of the anti-pd-1 and anti-pd-l1 immune checkpoint antibodies. ann oncol. 2015;26(12):2375-2391. 2. robert c, schachter j, long gv, et al. pembrolizumab versus ipilimumab in advanced melanoma. n engl j med. 2015;372(26):25212532. 3. weber js, hodi fs, wolchok jd, et al. safety profile of nivolumab monotherapy: a pooled analysis of patients with advanced melanoma. j clin oncol. 2017;35(7):785-792. 4. hua c, boussemart l, mateus c, et al. association of vitiligo with tumor response in patients with metastatic melanoma treated with pembrolizumab. jama dermatol. 2016;152(1):45-51. 5. teulings he, limpens j, jansen sn, et al. vitiligo-like depigmentation in patients with stage iii-iv melanoma receiving immunotherapy and its association with survival: a systematic review and meta-analysis. j clin oncol. 2015;33(7):773-781. 6. us department of health and human services. common terminology criteria for adverse events (ctcae) version 4.0. 2009. https://evs.nci.nih.gov/ftp1/ctcae/ctcae_4.03/ archive/ctcae_4.0_2009-0529_quickreference_8.5x11.pdf. 7. belum vr, benhuri b, postow ma, et al. characterisation and management of dermatologic adverse events to agents targeting the pd-1 receptor. eur j cancer. 2016;60:12-25. 8. minkis k, garden bc, wu s, pulitzer mp, lacouture me. the risk of rash associated with ipilimumab in patients with cancer: a systematic review of the literature and meta-analysis. j am acad dermatol. 2013;69(3):e121-128. 9. hwang s. difference in skin toxicities observed in patients with metastatic melanoma treated with combined pembrolizumab and ipilimumab vs. pembrolizumab alone. 50th annual scientific meeting of the australasian college of dermatologist; 2017; sydney, australia. 10. curry jl, tetzlaff mt, nagarajan p, et al. diverse types of dermatologic toxicities from immune checkpoint blockade therapy. j cutan pathol. 2017;44(2):158-176. 11. collins lk, chapman ms, carter jb, samie fh. cutaneous adverse effects of the immune checkpoint inhibitors. curr probl cancer. 2017;41(2):125-128. 12. robert c, long gv, brady b, et al. nivolumab in previously untreated melanoma without braf mutation. n engl j med. 2015;372(4):320-330. 13. motzer rj, rini bi, mcdermott df, et al. nivolumab for metastatic renal cell carcinoma: results of a randomized phase ii trial. j clin oncol. 2015;33(13):1430-1437. 14. garon eb, rizvi na, hui r, et al. pembrolizumab for the treatment of non-small-cell lung cancer. n engl j med. 2015;372(21):2018-2028. mailto:mcevoy.marian@mayo.edu https://evs.nci.nih.gov/ftp1/ctcae/ctcae_4.03/archive/ctcae_4.0_2009-05-29_quickreference_8.5x11.pdf https://evs.nci.nih.gov/ftp1/ctcae/ctcae_4.03/archive/ctcae_4.0_2009-05-29_quickreference_8.5x11.pdf https://evs.nci.nih.gov/ftp1/ctcae/ctcae_4.03/archive/ctcae_4.0_2009-05-29_quickreference_8.5x11.pdf skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 116 15. robert c, ribas a, wolchok jd, et al. antiprogrammed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dosecomparison cohort of a phase 1 trial. lancet. 2014;384(9948):1109-1117. 16. brahmer j, reckamp kl, baas p, et al. nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. n engl j med. 2015;373(2):123-135. 17. topalian sl, hodi fs, brahmer jr, et al. safety, activity, and immune correlates of anti-pd-1 antibody in cancer. n engl j med. 2012;366(26):2443-2454. 18. troyanova-slavkova s, eickenscheidt l, dumann k, kowalzick l. [initially undetected de novo psoriasis triggered by nivolumab for metastatic base of the tongue carcinoma]. hautarzt. 2018;69(8):674-680. 19. om a, cardon b, cohen g. psoriasiform eruption on the face and extremities associated with nivolumab therapy. jaad case rep. 2018;4(4):373-375. 20. bonigen j, raynaud-donzel c, hureaux j, et al. anti-pd1-induced psoriasis: a study of 21 patients. j eur acad dermatol venereol. 2017;31(5):e254-e257. 21. lomax aj, ge l, anand s, mcneil c, lowe p. bullous pemphigoid-like reaction in a patient with metastatic melanoma receiving pembrolizumab and previously treated with ipilimumab. australas j dermatol. 2016;57(4):333-335. 22. tanita k, fujimura t, kambayashi y, et al. intensity-modulated radiotherapy triggers onset of bullous pemphigoid in a patient with advanced melanoma treated with nivolumab. case rep oncol. 2018;11(1):114-118. 23. matsumoto y, kadono t, matsuoka m, et al. disseminated erythema with intense and selective inflammation of sweat gland and lichenoid drug eruption during nivolumab therapy. j dermatol. 2018;45(2):e33-e34. 24. shao k, mcgettigan s, elenitsas r, chu ey. lupus-like cutaneous reaction following pembrolizumab: an immune-related adverse event associated with anti-pd-1 therapy. j cutan pathol. 2018;45(1):74-77. 25. barbosa ns, wetter da, wieland cn, shenoy nk, markovic sn, thanarajasingam u. scleroderma induced by pembrolizumab: a case series. mayo clin proc. 2017;92(7):1158-1163. 26. burillo-martinez s, morales-raya c, prietobarrios m, rodriguez-peralto jl, ortiz-romero pl. pembrolizumab-induced extensive panniculitis and nevus regression: two novel cutaneous manifestations of the postimmunotherapy granulomatous reactions spectrum. jama dermatol. 2017;153(7):721722. 27. tetzlaff mt, jazaeri aa, torres-cabala ca, et al. erythema nodosum-like panniculitis mimicking disease recurrence: a novel toxicity from immune checkpoint blockade therapy-report of 2 patients. j cutan pathol. 2017;44(12):1080-1086. 28. helm mf, bax mj, bogner pn, chung cg. metastatic melanoma with features of blue nevus and tumoral melanosis identified during pembrolizumab therapy. jaad case rep. 2017;3(2):135-137. 29. bari o, cohen pr. tumoral melanosis associated with pembrolizumab-treated metastatic melanoma. cureus. 2017;9(2):e1026. 30. imafuku k, yoshino k, ymaguchi k, tsuboi s, ohara k, hata h. nivolumab therapy before vemurafenib administration induces a severe skin rash. j eur acad dermatol venereol. 2017;31(3):e169-e171. 31. saw s, lee hy, ng qs. pembrolizumab-induced stevens-johnson syndrome in non-melanoma patients. eur j cancer. 2017;81:237-239. 32. nayar n, briscoe k, fernandez penas p. toxic epidermal necrolysis-like reaction with severe satellite cell necrosis associated with nivolumab in a patient with ipilimumab refractory metastatic melanoma. j immunother. 2016;39(3):149-152. 33. gillis nk, hicks jk, bell gc, daly aj, kanetsky pa, mcleod hl. incidence and triggers of stevens-johnson syndrome and toxic epidermal necrolysis in a large cancer patient cohort. j invest dermatol. 2017;137(9):2021-2023. 34. mirza s, hill e, ludlow sp, nanjappa s. checkpoint inhibitor-associated drug reaction with eosinophilia and systemic symptom syndrome. melanoma res. 2017;27(3):271-273. 35. reule rb, north jp. cutaneous and pulmonary sarcoidosis-like reaction associated with ipilimumab. j am acad dermatol. 2013;69(5):e272-e273. 36. cho m, nonomura y, kaku y, dainichi t, otsuka a, kabashima k. generalized lichen nitidus following anti-pd-1 antibody treatment. jama dermatol. 2018;154(3):367-369. 37. velasco-tamariz v, burillo-martinez s, prietobarrios m, calleja-algarra a, rodriguez-peralto jl, ortiz-romero pl. widespread biphasic amyloidosis related to ipilimumab treatment for metastatic melanoma. int j dermatol. 2017;56(9):e189-e191. 38. kyllo rl, parker mk, rosman i, musiek ac. ipilimumab-associated sweet syndrome in a skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 117 patient with high-risk melanoma. j am acad dermatol. 2014;70(4):e85-e86. 39. hwang sj, carlos g, wakade d, sharma r, fernandez-penas p. ipilimumab-induced acute generalized exanthematous pustulosis in a patient with metastatic melanoma. melanoma res. 2016;26(4):417-420. 40. kang a, yuen m, lee dj. nivolumab-induced systemic vasculitis. jaad case rep. 2018;4(6):606-608. 41. kottschade l. management of immune-related adverse events from immune checkpoint inhibitor therapy. in: dong h, markovic sn, eds. the basics of cancer immunotherapy. springer international publishing; 2018:143-152. 42. wang ll, patel g, chiesa-fuxench zc, et al. timing of onset of adverse cutaneous reactions associated with programmed cell death protein 1 inhibitor therapy. jama dermatol. 2018;154(9):1057-1061. 43. brahmer jr, lacchetti c, thompson ja. management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: american society of clinical oncology 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2015;151(11):1206-1212. skin march 2018 volume 2 issue 2 copyright 2018 the national society for cutaneous medicine 122 original research comparison of survey modality and response rate in dermatologists’ perceptions and opinions of sunscreens alex m. glazer md a , aaron s. farberg md b , ryan m. svoboda md ms c , darrell s. rigel md ms c a university of arizona college of medicine, division of dermatology, tucson, az b department of dermatology, icahn school of medicine at mount sinai, new york, ny c national society for cutaneous medicine, new york, ny d ronald o. perelman department of dermatology, nyu school of medicine, new york, ny abstract background. survey instruments are valuable tools for research and provide insight into real-world practice and areas of knowledge deficits in ways that traditional observational studies and randomized trials cannot. despite some experts espousing survey response rates ≥60% as valid, there is no consensus as to what an adequate response rate is for a scientific survey. furthermore, little is known what effect the interaction of survey administration modality and response rate has on results. objective. to compare the results of differing survey modalities (which typically feature different response rate ranges). methods. a validated, 21-item survey assessing perceptions of, recommendations regarding, and usage of sunscreen was distributed to three samples of dermatologists using three different modalities: pen/paper via mail, online via email, and in real-time via an audience response system at a national conference. results. response rates varied widely by survey modality (30% mail, 9% email 95% live). however, dermatologists’ responses to individual survey questions were largely consistent across modalities, with a statistically significant difference seen for only three questions (recommending sunscreens based on cosmetic elegance, recommending sunscreens based on photostability, and recommending vitamin d supplementation as a means to avoid sun exposure. conclusions. in this study evaluating dermatologists’ perceptions of, recommendations for, and personal use of sunscreen, survey results were largely consistent across three different modalities (mail, email, live) despite widely variable response rates, from 9% to 95%. these results suggest that when a scientific survey sample is representative of the target population, minimum response rate and survey modality appear to have negligible impact on results. skin march 2018 volume 2 issue 2 copyright 2018 the national society for cutaneous medicine 123 physician management practices, knowledge gaps, and target areas for improvement are often assessed through research tools such as surveys. surveys can be conducted using multiple methods including mail, internet, live audience response systems, or face-to-face interviews. studies specifically comparing the differences in medical survey results based upon mode of administration are lacking. there is no consensus as to what an adequate response rate is for a survey to be considered publishable in scientific literature. there have been suggestions that high response rates are required for results to be valid and the jama network suggests a minimum rate of 60% for publication. 1,2 the purpose of this study was to compare differing survey modalities with lower response rates to assess if such high rates should be required. a 21 question survey assessing dermatologists’ perceptions, recommendation factors, and usage of sunscreen was derived and validated. the survey was administered between may and july 2016 to different subsets of us dermatologists using 1) a mailed paper survey (mailed to 500 randomly selected us aad members), 2) a real-time computer administered survey at a national dermatology conference (165 us dermatologists) 3 , and 3) an emailed survey (sent to 6350 us dermatologists). 4 stratification measures were taken to minimize respondent overlap. results for each question were compared by modality using chi square and proportional difference testing where appropriate. the estimated sample size (n) to test a proportion to achieve a 95% confidence interval of less than 5% was computed using the standard statistical formula: where n=population size and p=0.85 (lower a priori estimate of average affirmative response) and determined for our surveys (mail [28.2%], email [3.0%] and live [54.3%]). the survey was institutional review board exempt. the survey questions and comparative results are presented in the table 1. the response rates for each modality (mail 30%, email 9%, live 95%) exceeded the determined threshold for validity. respondent demographics were representative of us aad membership. only 3 of 63 responses had statistically significant (but not clinically relevant) differing responses. all other questions had results that were statistically consistent. determining dermatologists’ perceptions, recommendations and usage of sunscreen appears to be independent of survey modality. despite differing sample sizes and response rates for each modality employed, the same results were generally achieved. introduction methods results discussion skin 124 table 1. dermatologists’ perceptions, recommendations, and use of sunscreen compared through differing survey modalities. dermatologists’ sunscreen perceptions live interactive audience (n=156) mail survey (n=150) email survey (n=540) regular use of sunscreen helps lower skin cancer risk. 97% (ci: 93-99%) 100% (ci: 98-100%) 99% (ci: 98-100%) regular use of sunscreen helps reduce subsequent photoaging. 100% (ci: 98-100%) 100% (ci: 98-100%) 99% (ci: 98-100%) consider fda approved sunscreens currently available in the us safe. 96% (ci: 92-99%) 95% (ci: 91-98%) 96% (ci: 94-97%) consider oxybenzone in sunscreen to be safe. 91% (ci: 85-95%) 89% (ci: 83-93%) 86% (ci: 83-89%) consider retinyl palmitate in sunscreen to be safe. 87% (ci: 81-82%) 85% (ci: 79-91%) 85% (ci: 82-88%) patients generally under-apply sunscreen. 99% (ci: 95-100%) 99% (ci: 95-100%) 96% (ci: 94-97%) high spf sunscreens (spf 50+) provide additional margin of safety. 83% (ci: 77-89%) 76% (ci: 68-83%) 74% (ci: 70-78%) best form of sunscreen is one used regularly. 99% (ci: 95-100%) 97% (ci: 93-99%) 97% (ci: 95-98%) dermatologists’ sunscreen recommendations and factors spf criteria used for sunscreen recommendation: 99% (ci: 95-100%) 98% (ci: 94-100%) 96% (ci: 94-97%) broad spectrum criterion used for sunscreen recommendation: 96% (ci: 92-99%) 99% (ci: 96-100%) 98% (ci: 97-99%) cosmetic elegance/feel criterion used for sunscreen recommendation: 71% (ci: 63-78%)* 88% (ci: 82-93%) 85% (ci: 82-88%) photostability criteria used for sunscreen recommendation: 42% (ci: 34-51%)* 67% (ci: 59-74%) 68% (ci: 64-72%) recommend sunscreen containing: oxybenzone: 88% (ci: 82-93%) 86% (ci: 79-91%) 83% (ci: 80-86%) recommend sunscreen containing: retinyl palmitate: 78% (ci: 71-84%) 79% (ci: 72-86%) 80% (ci: 77-84%) recommend sunscreen containing: zinc oxide or titanium dioxide: 100% (ci: 98-100%) 100% (ci: 98-100%) 99% (ci: 98-100%) recommend sunscreen with spf 50 or higher: 97% (ci: 93-99%) 92% (ci: 86-96%) 92% (ci: 90-94%) recommend spray formulations: 73% (ci: 65-80%) 74% (ci: 66-81%) 69% (ci: 65-73%) recommend vitamin d by oral supplement rather than sun exposure. 80% (ci: 73-86%)* 86% (ci: 79-91%) 91% (ci: 88-93%) percentage of patients that sunscreen is recommended for: 79% for 80%+ of patients (ci:72-85%) 78% for 80%+ of patients (ci:71-84%) 79% for 80%+ of patients (ci:75-82%) spf level typically recommend to patients who are outdoors: 100% recommend spf30 or more (ci:98-100%) 35% recommend spf50 or more (ci:28-43%) 99% recommend spf30 or more (ci:95-100%) 37% recommend spf50 or more (ci:30-46%) 98% recommend spf30 of more (ci:96-99%) 36% recommend spf50 or more (ci:32-40%) dermatologists’ sunscreen self/family usage when outdoors, the spf level dermatologists typically choose: 100% choose spf30+ (ci:98-100%) 69% choose spf50+ (ci:61-76%) 100% choose spf30+ (ci:98-100%) 67% choose spf50+ (ci:59-74%) 99% choose spf30+ (ci:98-100%) 63% choose spf50+ (ci:59-67%) dermatologists typically wear sunscreen themselves: 76% at least half time (ci:69-83%) 53% daily (ci:45-61%) 77% at least half time (ci:70-84%) 43% daily (ci:35-52%) 82% at least half time (ci:79-85%) 44% daily (ci:40-48%) recommend family/friends use sunscreen to help protect their skin. 99% (ci:96-100%) 99% (ci:96-100%) 99% (ci:98-100%) skin march 2018 volume 2 issue 2 copyright 2018 the national society for cutaneous medicine 125 125 although all three surveys had different population sizes and response rates, because each met statistical thresholds and was demographically representative, the results were not materially different. standard inferential mathematical methods demonstrate that the percentage of responses required for a sample to be statistically valid varies inversely with the population of interest size. 5 for example, election polling typically utilizes a very small proportion to predict outcomes. 6 in fact, the reference cited to support a 60% minimum response rate was actually a “viewpoint” editorial based upon a paper sampling very small populations (and also asserts that the sample size percentage should decrease as the population size increases). 1 our findings confirm this in contrast to a fixed-minimum survey response rate of 60% that is being used in some journals independent of population size. 1,2 study limitations include possible nonresponder, selection, acquiescence and social desirability bias that could have affected the survey results and potentially impacted the comparisons. when surveying dermatologists’ sunscreen opinions, live, online and traditional mail surveys provided similar results. minimum response rates needed to achieve validity can be calculated as a function of population size using standard statistical methods when the sample is demographically representative of the studied population and should not be limited to a fixed minimum percentage. conflict of interest disclosures: none. funding: none corresponding author: alex m. glazer, md division of dermatology, university of arizona po box 245024 1515 n. campbell avenue tucson, az 85724-5024 212-685-3252 (office) alex.glazer@gmail.com references: 1. fincham je. response rates and responsiveness for surveys, standards, and the journal. am j pharm educ. 2008;72:article 43. 2. instructions for authors. the jama network website. http://jamanetwork.com/journals/ja ma/pages/instructions-for-authors. updated may 4, 2017. accessed may 17, 2017. 3. farberg as, glazer am, rigel ac, et al. dermatologists’ perceptions, recommendations, and use of sunscreen. jama dermatol. 2017;153(1):99-101. 4. farberg as, rigel ac, rigel ds. online survey of us dermatologists’ sunscreen opinions: perceptions, recommendation factors, and selfusage. j drugs dermatol. 2016;15(9):1121-1123. 5. survey research design. in: p.p. phillips, j.j. phillips, b. aaron (eds.) survey basics. astd press,alexandria (va); 2013. skin march 2018 volume 2 issue 2 copyright 2018 the national society for cutaneous medicine 126 126 6. gaissmaeier w, marewski jn. forecasting elections with mere recognition from small, lousy samples: a comparison of collective recognition, wisdom of crowds, and representative polls. judgment and decision making. 2011;6(1):73-88. abstract • introduction: secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin (il)-17a, has been shown to have significant efficacy in the treatment of moderate-to-severe plaque psoriasis and psoriatic arthritis, demonstrating a rapid onset of action and sustained responses, with a favorable safety profile. here, we report exposure-adjusted incidence rates (irs) for treatment-emergent adverse events per year from a pooled analysis of all secukinumab psoriasis trials to date (19 studies, 4674 patients, 10,061 patient-years exposure). • methods: adverse event (ae) irs (per 100 subject-years) were examined per year for subjects who received either secukinumab 300 mg or any dose of secukinumab, and for 1 year only, for subjects receiving placebo (pbo), etanercept (etn) 50 mg, or ustekinumab (ust) 45/90 mg. • results: the duration of exposure to any dose of secukinumab/secukinumab 300 mg (patient-years) was 4093.5/1467.4 at year 1, 2631.3/859.6 at year 2, 1659.6/423.0 at year 3, 1392.2/377.5 at year 4, and 291.6/90.0 at year 5. secukinumab pooled safety remained favorable over 5 years of treatment with no increase of aes over time. the irs of aes for patients receiving any dose of secukinumab/secukinumab 300 mg were 254.1/275.6 at year 1, 169.9/168.1 at year 2, 159.8/160.2 at year 3, 104.1/111.9 at year 4, and 12.0/13.9 at year 5. the most frequent aes with secukinumab over 5 years were nasopharyngitis, headache, and upper respiratory tract infection. the incidence of opportunistic infections, candida infections, neutropenia, major adverse cardiovascular events, crohn’s disease, ulcerative colitis, and malignant or unspecified tumors (excluding nonmelanoma skin cancer) were infrequent with secukinumab. additionally, secukinumab demonstrated a comparable pooled safety profile to that of pbo, etn, and ust over the course of 1 year. • conclusion: this comprehensive pooled analysis supports the favorable long-term safety profile of secukinumab in patients with psoriasis. introduction • psoriasis is a chronic immune-mediated skin disease typically requiring long-term treatment, thus longitudinal data establishing the safety of approved therapies are required • secukinumab is a fully human monoclonal antibody that selectively neutralizes il-17a, a key cytokine involved in the development of psoriasis. secukinumab has shown long-lasting efficacy and safety in the complete spectrum of psoriasis manifestations, including nails, scalp, palms and soles involvement and psoriatic arthritis1–5 • here we report exposure-adjusted incidence rates (irs) for treatment-emergent adverse events per year from a pooled analysis of all secukinumab psoriasis trials to date (19 studies, 4,674 secukinumab patients, ~10,000 patient-years exposure) methodology • adverse event (ae) irs (per 100 patient years) were examined per year for subjects who received either secukinumab 300 mg (every 4 weeks) or any dose of secukinumab (including subcutaneous 300 mg, 150 mg, 75 mg, 25 mg or intravenous infusion [1 and 3mg/kg]), and up to 1 year only for subjects receiving placebo (pbo), etanercept (etn) or ustekinumab (ust) per label use • aes were classified by meddra system organ class and preferred term • data from 9 phase 2 and 10 phase 3 randomized, double-blind clinical trials were examined* • a subject with multiple occurrences of the same ae in a one-year interval, or a prolonged occurrence of the same ae beyond a one-year interval, was counted once (i.e., in the year when the ae first occurred), while a subject with multiple occurrences of the same ae in different year intervals was counted for each year * phase 2 studies: a1302, a2102, a2103, a2204, a2211, a2212, a2220, a2223, a2225 (data from the a2211e1 extension study were also included); phase 3 studies: a2302, a2303, a2304, a2308, a2309, a2317, a2312, a3301, a2313, aus01 (data from the a2302e1 and a2304e1 extension studies were also included) • secukinumab pooled safety remained favorable over 5 years of treatment with no increase of aes over time (figure 1) • secukinumab demonstrated a comparable pooled safety profile to that of pbo, etn and ust over the course of 1 year (figure 1) conclusions • this comprehensive pooled analysis of 19 phase 2/3 trials supports the favorable long-term safety profile of secukinumab in patients with psoriasis • no new safety signals were identified for up to 5 years of treatment and there were no increases in yearly ae rates from year 1 • secukinumab’s safety profile was consistent with that established in previous phase 2/3 studies6 results • overall, baseline characteristics were comparable across treatments (table 1) table 1. baseline demographic and clinical characteristics in the pooled psoriasis population characteristic any secukinumab dose (n=4674) secukinumab 300 mg (n=1773) etanercept (n=323) ustekinumab (n=336) placebo (n=1090) age, years 45.6 ± 13.1 45.8 ± 13.5 43.7 ± 13.0) 44.6 ± 13.6 45.6 ± 12.9 gender-male, n (%) 3127 (66.9) 1168 (65.9) 229 (70.9) 251 (74.7) 699 (64.1) race-caucasian, n (%) 3694 (79.0) 1396 (78.7) 216 (66.9) 285 (84.8) 861 (79.0) body weight, kg 87.1 ± 22.7 86.2 ± 22.2 84.5 ± 20.5 87.4 ± 22.1 87.1 ± 23.5 bmi, kg/m2 29.4 ± 6.8 29.2 ± 6.6 28.7 ± 5.9 29.1 ± 6.7 29.3 ± 7.2 pasi score 20.7 ± 10.6 21.0 ± 10.4 23.3 ± 9.8 21.5 ± 8.1 19.4 ± 10.9 bsa affected, % 30.4 ± 19.1 32.0 ± 19.1 33.7 ± 18.0 32.0 ± 16.8 29.1 ± 18.3 obesity class, n (%) overweight (bmi 25–29.9) 1507 (32.2) 571 (32.2) 128 (39.6) 111 (33.0) 373 (34.2) obesity class i (bmi 30–39.9) 974 (20.8) 385 (21.7) 62 (19.2) 76 (22.6) 213 (19.5) obesity class ii (bmi 35–39.9) 460 (9.8) 186 (10.5) 31 (9.6) 31 (9.2) 99 (9.1) obesity class iii (bmi ≥40) 338 (7.2) 113 (6.4) 12 (3.7) 17 (5.1) 76 (7.0) psoriatic arthritis present, n (%) 833 (17.8) 324 (18.3) 45 (13.9) 52 (15.5) 182 (16.7) cv disease risk factors, n (%) hypertension 1087 (23.3) 479 (27.0) 67 (20.7) 85 (25.3) 218 (20.0) hyperlipidemia 666 (14.3) 302 (17.0) 43 (13.3) 49 (14.6) 141 (12.9) myocardial infarction 72 (1.5) 33 (1.9) 5 (1.5) 6 (1.8) 17 (1.6) latent tb*, n (%) 134 (2.9) 63 (3.6) 16 (5.0) 13 (3.9) 24 (2.2) ibd**, n (%) 17 (0.4) 5 (0.3) 0 (0) 1 (0.3) 6 (0.6) history of cancer (other than skin), n (%) 29 (0.6) 13 (0.7) 0 (0) 1 (0.3) 5 (0.5) history of skin cancer, n (%) 3 (0.1) 1 (0.1) 0 (0) 0 (0) 0 (0) data are presented as mean ± sd unless otherwise stated. *patients diagnosed with latent tb at enrollment received prophylactic treatment. **patients with a medical history of ibd (including crohn’s disease and ulcerative colitis) bmi, body mass index; bsa, body surface area; cv, cardiovascular; ibd, inflammatory bowel disease; pasi, psoriasis area severity index; sd, standard deviation; tb, tuberculosis • of the 4,674 patients who were exposed to any secukinumab dose, 3,423 patients were exposed for at least more than 1 year (table 2) table 2. duration of patient exposure and a summary of exposure-adjusted incidence rates for total aes year 1 year 2 year 3 year 4 year 5 secukinumab etn 50 mg (n=323) ust 45/90 mg (n=336) pbo (n=1090) secukinumab secukinumab secukinumab secukinumab any dose (n=4674) 300 mg (n=1773) any dose (n=3423) 300 mg (n=1188) any dose (n=1972) 300 mg (n=572) any dose (n=1522) 300 mg (n=397) any dose (n=909) 300 mg (n=263) duration of exposure (patient-years) 4093.5 1467.4 296.9 318.1 301.2 2631.3 859.6 1659.6 423.0 1392.2 377.5 291.6 90.0 total aes 254.1 275.6 245.7 252.2 355.8 169.9 168.1 159.8 160.2 104.1 111.9 12.0 13.9 non-fatal serious aes 8.6 8.9 6.9 8.2 9.1 7.6 7.3 7.4 8.8 5.8 6.8 0.7 1.1 ae, adverse event; etn, etanercept; pbo, placebo; ust, ustekinumab secukinumab’s pooled and long-term safety: analysis of 19 psoriasis clinical trials up to 5 years of treatment pcm van de kerkhof1, k reich2, cl leonardi3, a blauvelt4, nn mehta5, tf tsai6, r you7, p papanastasiou8, m milutinovic8, cem griffiths9 1department of dermatology, radboud university nijmegen medical centre, nijmegen, the netherlands; 2dermatologikum hamburg and georg-august-university, göttingen, germany; 3saint louis university health sciences center, st. louis, mo, usa; 4oregon medical research center, portland, or, usa; 5national heart, lung, and blood institute, bethesda, md, usa; 6national taiwan university hospital, national taiwan university college of medicine, taipei, taiwan; 7china novartis institutes for biomedical research, shanghai, china; 8novartis pharma ag, basel, switzerland; 9dermatology centre, salford royal hospital, university of manchester, manchester academic health science centre, manchester, uk download document at the following url: http://novartis.medicalcongressposters.com/default.aspx?doc=4031a and via text message (sms) text: q4031a to: 8nova (86682) us only +18324604729 north, central and south americas; caribbean; china +447860024038 uk, europe & russia +46737494608 sweden, europe scan to download a reprint of this poster references 1. hueber w et al. sci transl med. 2010;2:52ra72. 2. langley rg et al. n engl j med. 2014;371:326–338. 3. thaci d et al. jaad. 2015;73:400. 4. blauvelt et al. jaad. 2017;76:60–69. 5. mease et al. n engl j med. 2015;373:1329–39. 6. van de kerkhof et al. j am acad dermatol. 2016;75(1):83–98. disclosures p van de kerkhof: clinical trials, consultant and/or speaker for abbvie, almirall, amgen, celgene, centocor, eli lilly, galderma, janssen-cilag, leo pharma, mitsubishi, novartis, pfizer, philips, and sandoz. k reich: advisor and/or paid speaker for and/or participated in clinical trials sponsored by abbvie, amgen, biogen, boehringer-ingelheim, celgene, centocor, covagen, forward pharma, glaxosmithkline, janssen-cilag, leo, lilly, medac, merck sharp & dohme corp., novartis, ocean pharma, pfizer, regeneron, takeda, ucb pharma, xenoport. cl leonardi: consultant for abbvie, amgen, dermira, janssen, eli-lilly, leo, sandoz, ucb and pfizer; investigator for actavis, abbvie, amgen, celgene, coherus, dermira, eli lilly, galderma, janssen, merck, pfizer, sandoz, stiefel, leo, novartis, and wyeth and has participated in speaker bureaus for abbvie, celgene, lilly. a blauvelt: scientific consultant and clinical study investigator for abbvie, aclaris, allergan, almirall, amgen, boehringer ingelheim, celgene, dermavant, dermira, eli lilly, genentech/roche, glaxosmithkline, janssen, leo, merck sharp & dohme, novartis, pfizer, purdue pharma, regeneron, sandoz, sanofi genzyme, sienna pharmaceuticals, sun pharma, ucb, valeant, vidac; speaker for eli lilly and company, janssen, regeneron, sanofi genzyme. nn mehta: full time us government employee and receives research grants to the nhlbi from abbvie, janssen, novartis and celgene. tf tsai: consultant for abbvie, celgene, eli lilly, janssen, leo pharma, galderma, novartis, boehringer ingelheim, and pfizer. r you, p papanastasiou, m milutinovic: employees of novartis. cem griffiths: advisor and/or research grants from abbvie, almirall, bms, gsk, galderma, janssen, leo pharma, msd, pfizer, novartis, sandoz, eli lilly, sanofi-regeneron, roche, l’oreal, dsm, clarins, walgreens boots alliance, ucb pharma. acknowledgements the authors thank the patients and their families and all investigators and their staff for participation in the study. oxford pharmagenesis, inc., newtown, pa, usa provided assistance with layout and printing the poster; this support was funded by novartis pharmaceuticals corporation, east hanover, nj. the authors had full control of the contents of this poster. this research was funded by novartis pharma ag, basel, switzerland. originally presented at: 8th international psoriasis from gene to clinic congress, london, uk; november 30–december 2, 2017. poster presented at: 13th annual winter clinical dermatology conference, maui, hi, usa; january 12–17, 2018. figure 1. exposure-adjusted incidence rates for treatment-emergent aes nasopharyngitis headache frequent aes selected aes 27.4 28.4 35.9 31.2 35.9 22.7 21.2 23.2 24.1 14.4 11.8 1 3.4 0 10 20 30 40 50 year 1 year 2 year 3 year 4 year 5 e xp os ur ead ju st ed i r ( 95 % c i) 10.5 12.6 15 14.6 23.7 5.1 5.4 4.8 4.3 3.4 4.9 0 00 5 10 15 20 25 30 35 year 1 year 2 year 3 year 4 year 5 e xp os ur ead ju st ed i r ( 95 % c i) upper respiratory tract infection total infections and infestations* opportunistic infections neutropenia crohn’s disease malignant or unspecified tumors (excluding nmsc) 8.8 9.1 5.9 9.9 8.8 7.2 7.3 6.9 6.1 5.2 5.5 0 00 2 4 6 8 10 12 14 16 year 1 year 2 year 3 year 4 year 5 e xp os ur ead ju st ed i r ( 95 % c i) 92.3 99.5 91.5 96.1 103.7 73.4 78.2 72.2 73.6 50.8 55.9 2.4 4.50 20 40 60 80 100 120 year 1 year 2 year 3 year 4 year 5 e xp os ur ead ju st ed i r ( 95 % c i) there were no tuberculosis infections or reactivations 0.2 0.2 0.34 0.31 0.33 0.08 0.12 0 0 0.07 0 0 00 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5 5.5 6 year 1 year 2 year 3 year 4 year 5 e xp os ur ead ju st ed i r ( 95 % c i) 0.5 0.5 1.4 0.0 0.0 0.3 0.1 0.2 0.0 0.1 0.0 0.0 0.00 0.5 1 1.5 2 2.5 3 3.5 4 4.5 year 1 year 2 year 3 year 4 year 5 e xp os ur ead ju st ed i r ( 95 % c i) mace 0.4 0.5 0.3 0.3 1.3 0.1 0.1 0.3 0.5 0.4 0.0 0.0 0.00 0.5 1 1.5 2 2.5 3 3.5 4 4.5 year 1 year 2 year 3 year 4 year 5 e xp os ur ead ju st ed i r ( 95 % c i) 0.1 0.1 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.00 0.5 1 1.5 2 2.5 3 3.5 4 4.5 year 1 year 2 year 3 year 4 year 5 e xp os ur ead ju st ed i r ( 95 % c i) ulcerative colitis 0.2 0.1 0.3 0.0 0.0 0.2 0.4 0.1 0.2 0.1 0.3 0.0 0.00 0.5 1 1.5 2 2.5 3 3.5 4 4.5 year 1 year 2 year 3 year 4 year 5 e xp os ur ead ju st ed i r ( 95 % c i) 0.5 0.4 0.3 0.3 0.3 0.3 0.4 0.5 0.2 0.2 0.0 0.0 0.00 0.5 1 1.5 2 2.5 3 3.5 4 4.5 year 1 year 2 year 3 year 4 year 5 e xp os ur ead ju st ed i r ( 95 % c i) any secukinumab etanercept ustekinumab placebosecukinumab 300 mg any secukinumab etanercept ustekinumab placebosecukinumab 300 mg candida infection 3.1 4.7 1.4 1.6 1.7 2.0 3.6 1.4 1.9 1.5 1.3 0.3 1.1 0 1 2 3 4 5 6 7 year 1 year 2 year 3 year 4 year 5 e xp os ur ead ju st ed i r ( 95 % c i) *there was no reactivation of latent tuberculosis in any of the included studies ae, adverse event; ci, confidence interval; ir, incidence rate per 100 patient-years; mace, major adverse cardiovascular events; nmsc, non-melanoma skin cancer skin december 2018 volume 2 supplemental issue copyright 2018 the national society for cutaneous medicine 97 rising derm stars association of pemphigus and pemphigoid with osteoporosis and pathological fractures raj chovatiya md, phd1, jonathan silverberg md, phd, mph1 1department of dermatology, northwestern university feinberg school of medicine, chicago, il background: pemphigus and pemphigoid are two groups of autoimmune bullous disease (aibd) associated with high morbidity and mortality. while there is no cure for either condition, a mainstay for treatment is long-term systemic corticosteroids that can decrease bone mineral density (bmd). patients with pemphigus and pemphigoid likely have additional risk factors for decreased bmd, including chronic inflammation. osteoporosis and skeletal fractures resulting from decreased bmd can lead to significant morbidity, hospitalization, decreased quality of life, and mortality. however, no large-scale studies have rigorously examined the association of aibd with osteoporosis and fractures. objective: the goal of our study was to determine whether pemphigus and pemphigoid are associated with osteoporosis and fracture in the u.s. population and how this affects admission rates and cost of care. methods: we performed a cross-sectional study of 198,102,435 children and adults, including 4,502 with pemphigus and 8,863 with pemphigoid, from the 2006-2012 national emergency department sample (neds), which is comprised of 20% of all emergency care visits throughout the united states. results: patients with pemphigus or pemphigoid were more likely to be female, older, evenly distributed across income quartiles, use medicare as the primary source of payment, and have a history of long-term steroid use. a pooled analysis across all 7 years showed that patients with pemphigus had significantly higher odds (multivariate logistic regression including age, sex, primary payer, income quartile, history of long-term steroids; or, 95% ci) of diagnosis with osteopenia (2.200, 1.5903.045), osteoporosis (2.536, 2.159-2.978), osteomalacia (29.699, 4.049-217.834), and pathologic fracture (2.035, 1.422-2.912) similarly, patients with pemphigoid had significantly higher odds of diagnosis with osteoporosis (1.550, 1.392-1.727) and pathologic fracture (1.517, 1.222-1.884). patients with pemphigus additionally had significantly higher odds of diagnosis with femur fracture (1.459, 1.125-1.893) and vertebral fracture (1.464 1.060-2.023). significant two-way interactions were detected between both pemphigus and pemphigoid and history of long-term steroid use on osteopenia, osteoporosis, and pathologic fracture. the rate of inpatient admission (% frequency, 95% ci) in patients with both pemphigus and fracture (96.4, 89.4100.0) and pemphigoid and fracture (90.9, skin december 2018 volume 2 supplemental issue copyright 2018 the national society for cutaneous medicine 98 80.4-100.0) was significantly higher than in those without fracture. the yearly inflation adjusted cost of combined ed and inpatient care was consistently and significantly higher in patients with pemphigus or pemphigoid and fracture compared to those without fracture. limitations: data on severity and treatments of pemphigus and pemphigoid were not available. conclusion: pemphigus and pemphigoid were associated with an increased risk of osteoporosis and pathologic fractures. this remained significant even after controlling for history of long-term steroid use, suggesting other disease intrinsic and extrinsic factors may underlie this increased risk (e.g. chronic inflammation, medication, lifestyle). patients with either pemphigus or pemphigoid and fracture also had higher admission rates and higher overall inflation adjusted cost of care. we propose that patients with pemphigus and pemphigoid constitute a significant, previously underrecognized public health burden due to risk for fractures, and they may benefit from early inventions (i.e. early bone density scans, adjustments in steroid dose, vitamin supplementation, referral to endocrinologist) from their primary physician – the dermatologist. skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 141 rising derm stars® characterizing the alopecia areata microbiome margit juhász, md, msc1, natasha atanaskova mesinkovska, md, phd 1university of california, irvine, department of dermatology, irvine, ca background: alopecia areata (aa) is an inflammatory, non-scarring hair loss resulting from autoimmune attack of the hair follicle, affecting as much as 2% of the population. researchers have not determined the exact pathogenesis of aa, but hypotheses include imbalances in innate immunity, environmental insults, and genetic predisposition. the microbiome is a community of commensal and pathogenic microorganisms that live on and within our bodies. with growing evidence that the microbiome plays a significant role in inflammatory skin conditions such as atopic dermatitis and psoriasis, recent cases postulate that the gut microbiome plays a role in aa development. methods: in this pilot study, we aim to characterize the local (scalp) and global (gut) microbiome of aa patients and determine if there are significant differences when compared to healthy controls. microbiome samples were collected from 25 subjects with aa and 25 healthy controls living in southern california at a single, academic medical center; controls were age, gender and racematched to alopecia patients. at the time of sample collection, all subjects were required to have no active gastrointestinal disease. scalp swabs and stool samples were obtained from each subject. after dna was isolated from each sample, 16s rna and internal transcribed spacer (its) libraries were created to identify bacterial and fungal taxonomy, respectively. multi-variant analysis comparing the alopecia to control microbiomes was performed. results: aa subjects were 40.3 ± 14.7 years old, female (72%) and identified as caucasian (60%). there were no significant differences noted in the demographic makeup of the alopecia and control groups. significant differences were noted in both the scalp and gut microbiome of alopecia patients compared to controls. alopecia patients’ scalp samples had significantly decreased firmicutes (p<0.05) and increased actinobacteria trending to significance, while their gut microbiome was significant for decreased bacteroides (p<0.05) and increased firmicutes trending to significance. conclusion: microbiome dysbiosis may cause inappropriate systemic immune response and inflammation leading to autoimmune alopecia in predisposed patients. it is our hope that this preliminary data may be used in the future to characterize changes in the scalp and gut microbiome that may be related to aa disease severity, patient dietary practices, and even predict prognosis and/or therapeutic response. skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 142 references: 1. adams, rl, miletto, m, taylor, jw, bruns, td. the diversity and distribution of fungi on residential surfaces. plos one. 8:e78866, 2013. 2. findley, k, oh, j, yang, j, conlan, s, et al. topographic diversity of fungal and bacterial communities in human skin. nature. 498:367-70, 2013. 3. hayashi, a, mikami, y, miyamoto, k, kamada, n, et al. intestinal dysbiosis and biotin deprivation induce alopecia through overgrowth of lactobacillus murinis in mice. 20(7):1513-24, 2017. 4. rebello, d, wang, e, yen, e, lio, p, kelly, c. hair growth in two alopecia patients after fecal microbiota transplant. acg case reports journal. 4(e107):doi:10.14309/crj.2017.107, 2017. 5. sinha, r, chen, j, amir, a, vogtmann, e, et al. collecting fecal samples for microbiome analyses in epidemiology studies. cancer epidemiol biomarkers prev. 25(2):407-16, 2016. skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 143 figure 1: comparison of the scalp bacterial microbiome from alopecia patients to healthy controls reveals significantly decreased firmicutes (p=0.00063) in alopecia samples. synopsis z seborrheic keratoses (sks) are benign yet aesthetically bothersome cutaneous lesions found mainly on the trunk, head, and neck1 z hydrogen peroxide topical solution 40% (w/w) (hp40) is the first topical treatment approved by the us food and drug administration for adults with raised sks2,3 — limited information is currently available regarding hp40 treatment in patients with skin of color z two randomized, double-blind, vehicle-controlled, parallelgroup phase 3 studies were conducted to investigate the safety and efficacy of hp40 compared with vehicle for the treatment of sks — at visit 1 of both trials, investigators determined the fitzpatrick skin type of all eligible study patients objective z we conducted a post hoc, pooled analysis of data from the two phase 3 pivotal clinical trials to evaluate the safety and tolerability of hp40 treatment in patients with skin of color, defined as having fitzpatrick skin types ≥iv materials and methods patients z this was a pooled, post hoc analysis of data from two phase 3, multicenter, randomized, double-blind, vehicle-controlled studies (nct02667236, nct02667275) z eligible patients were required to be ≥18 years of age and have 4 target sks (≥1 on the face and ≥1 on the trunk or extremities) — for the current analysis, patients were also required to have a fitzpatrick skin type of iv, v, or vi study design z both studies were vehicle-controlled and had a parallel-group design (figure 1) — patients were randomized to receive hp40 or vehicle — treatments were administered at visit 2 (all patients) and visit 4 (if the physician lesion assessmenttm [pla] grade was >0) • details of the validated pla tool are summarized in table 1 — the pla was performed at visits 1, 2, 4, 6, 7, and 8 z safety was assessed at all visits figure 1. study design sc re en in g patients with sk (≥4 evaluable lesions) vehicle 15 weeks r an d o m iz at io n 1 hp40 82 3 5 6 7visit: 4 boxed visits: treatment administered. hp40, hydrogen peroxide topical solution 40% (w/w); sk, seborrheic keratosis. table 1. pla scoring grade description 0 clear: no visible sk leison 1 near clear: a visible sk lesion with a surface appearance different from the surrounding skin (not elevated) 2 thin: a visible sk lesion (thickness ≤1 mm) 3 thick: a visible sk lesion (thickness >1 mm) pla, physician lesion assessment; sk, seborrheic keratosis. safety endpoints z safety assessments included treatment-related treatmentemergent adverse events (teaes) and local skin reactions (lsrs), which were evaluated by patients and clinical trial investigators — at visits 2 and 4, patients rated lsrs at 10 minutes posttreatment, and investigators rated lsrs at 20 minutes posttreatment results patient characteristics z a total of 97 patients with fitzpatrick skin types of iv, v, or vi were included in the pooled analysis (hp40, n=39; vehicle, n=58) z baseline demographics were similar between the hp40 and vehicle treatment groups (table 2) table 2. patient characteristics characteristic vehicle (n=58) hp40 (n=39) age, y mean ± sd 67.4 ± 9.02 67.2 ± 9.64 age group, y 18–55 3 (5.2) 3 (7.7) 56–70 35 (60.3) 21 (53.8) ≥71 20 (34.5) 15 (38.5) gender female 28 (48.3) 20 (51.3) race white 48 (82.8) 32 (82.1) african american 4 (6.9) 4 (10.3) asian 6 (10.3) 2 (5.1) other 0 1 (2.6) ethnicity hispanic or latino 4 (6.9) 8 (20.5) not hispanic or latino 44 (75.9) 24 (61.5) missing data 10 (17.2) 7 (17.9) fitzpatrick skin type i–iii 0 0 iv 52 (89.7) 34 (87.2) v 5 (8.6) 5 (12.8) vi 1 (1.7) 0 data are reported as n (%) unless stated otherwise. safety z treatment-related teaes — in the pooled analysis, 1 (2.6%) patient treated with hp40 experienced a treatment-related teae of a postprocedural complication — no treatment-related teaes were observed in the vehicle group z investigatorand patient-reported lsrs (figure 2) — by visit 8 (day 106, end of study), no hp40-treated patients reported an lsr of pruritus or stinging and no investigator observed atrophy, edema, erosion, scarring, ulceration, or vesicles — most investigator-observed lsrs among hp40-treated target lesions at visit 8 were mild (crusting, 3.8%; erythema, 3.2%; hyperpigmentation, 11.5%; hypopigmentation, 2.6%; scaling, 3.8%) • investigators reported moderate crusting for 1 target lesion (0.6%) and moderate hyperpigmentation for 4 target lesions (2.6%) — no severe lsrs were reported at visit 8 references 1. del rosso jq. j clin aesthet dermatol. 2017;10:16-25. 2. eskata [package insert]. malvern, pa: aclaris therapeutics, inc.; 2017. 3. baumann ls, et al. j am acad dermatol. 2018;79:869-77. acknowledgments this study was funded by aclaris therapeutics, inc. editorial support for this poster was provided by peloton advantage, llc, parsippany, nj, and funded by aclaris therapeutics, inc. disclosures ch has conducted clinical trials for and participates in advisory boards for aclaris therapeutics, inc. et has conducted clinical trials for aclaris therapeutics. tmj is an investigator for aclaris therapeutics. mb is a statistical consultant to aclaris and owns stock in that company. js and sds are employees of aclaris therapeutics and may own stock/stock options in that company. email address for questions or comments: cphren@mindspring.com conclusions 1 treatment with hp40 was safe and well tolerated in patients with skin of color and sks on the face, extremities, and trunk 2 incidences of both investigatorand patientreported lsrs were similar between groups and most were mild 3 at the final study visit, no lsrs were severe, and all except crusting and hyperpigmentation were mild safety of hydrogen peroxide topical solution, 40% (w/w) in patients with skin of color and seborrheic keratoses: pooled analysis of two phase 3, randomized, doubleblind, vehicle-controlled, parallel-group studies catherine hren, md,1 eduardo tschen, md, mba,2 terry m. jones, md,3 mark bradshaw, phd,4 judith schnyder, mba,5 stuart d. shanler, md, faad, facms5 1cary dermatology center, cary, nc; 2academic dermatology associates, albuquerque, nm; 3j&s studies, inc., college station, tx; 4gcp-mb, llc, asbury park, nj; 5aclaris therapeutics, inc., wayne, pa presented at winter clinical dermatology conference, january 18–23, 2019, koloa, hawaii figure 2. frequencies of lsrs that occurred during treatment visits or end of study by visit, intensity, and treatment: (a) patient-reported lsrs; (b) investigator-reported lsrs stinging ta rg et s k l es io n s (% ) 0 20 40 60 80 100 mild moderate severe visit 2 pretreatment visit 2 posttreatment visit 4 pretreatment visit 4 posttreatment visit 8 end of study vehicle hp40vehicle hp40vehicle hp40vehicle hp40vehicle hp40 pruritusa ta rg et s k l es io n s (% ) 0 20 40 60 80 100 mild moderate severe visit 2 pretreatment visit 2 posttreatment visit 4 pretreatment visit 4 posttreatment visit 8 end of study vehicle hp40vehicle hp40vehicle hp40vehicle hp40vehicle hp40 b crusting ta rg et s k l es io n s (% ) 0 20 40 60 80 100 visit 2 pretreatment visit 2 posttreatment visit 4 pretreatment visit 4 posttreatment visit 8 end of study vehicle hp40vehicle hp40vehicle hp40vehicle hp40vehicle hp40 mild moderate severe edema ta rg et s k l es io n s (% ) 0 20 40 60 80 100 mild moderate severe visit 2 pretreatment visit 2 posttreatment visit 4 pretreatment visit 4 posttreatment visit 8 end of study vehicle hp40vehicle hp40vehicle hp40vehicle hp40vehicle hp40 erythema ta rg et s k l es io n s (% ) 0 20 40 60 80 100 mild moderate severe visit 2 pretreatment visit 2 posttreatment visit 4 pretreatment visit 4 posttreatment visit 8 end of study vehicle hp40vehicle hp40vehicle hp40vehicle hp40vehicle hp40 hyperpigmentation ta rg et s k l es io n s (% ) 0 20 40 60 80 100 mild moderate severe visit 2 pretreatment visit 2 posttreatment visit 4 pretreatment visit 4 posttreatment visit 8 end of study vehicle hp40vehicle hp40vehicle hp40vehicle hp40vehicle hp40 hypopigmentation ta rg et s k l es io n s (% ) 0 20 40 60 80 100 mild moderate severe visit 2 pretreatment visit 2 posttreatment visit 4 pretreatment visit 4 posttreatment visit 8 end of study vehicle hp40vehicle hp40vehicle hp40vehicle hp40vehicle hp40 scaling ta rg et s k l es io n s (% ) 0 20 40 60 80 100 mild moderate severe visit 2 pretreatment visit 2 posttreatment visit 4 pretreatment visit 4 posttreatment visit 8 end of study vehicle hp40vehicle hp40vehicle hp40vehicle hp40vehicle hp40 ulceration ta rg et s k l es io n s (% ) 0 20 40 60 80 100 mild moderate severe visit 2 pretreatment visit 2 posttreatment visit 4 pretreatment visit 4 posttreatment visit 8 end of study vehicle hp40vehicle hp40vehicle hp40vehicle hp40vehicle hp40 vesicles ta rg et s k l es io n s (% ) 0 20 40 60 80 100 mild moderate severe visit 2 pretreatment visit 2 posttreatment visit 4 pretreatment visit 4 posttreatment visit 8 end of study vehicle hp40vehicle hp40vehicle hp40vehicle hp40vehicle hp40 hp40, hydrogen peroxide topical solution 40% (w/w); lsr, local skin reaction. skin july 2021 1251 proof returned skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 403 research letter the impact of the covid-19 pandemic on skin cancers treated with mohs micrographic surgery: a retrospective analysis at a single united states academic institution laila f. abbas, ba1, jennifer wang, ba1, rajiv i. nijhawan, md1, divya srivastava, md1 1ut southwestern medical center, department of dermatology, dallas, texas the coronavirus disease 2019 (covid-19) pandemic led to changes in practice among skin cancer surgeons, especially through restrictions placed on elective procedures, leading to a negative impact on skin cancer care.1-4 preliminary studies in the united kingdom plastic surgery literature showed the short-term negative impact of the european lockdown on skin cancer outcomes, demonstrating that patients seen during the first wave of the pandemic had larger, more aggressive tumors with an increase in incomplete excision margins.1,5 prior studies in the united states literature have also shown that the covid-19 pandemic led to delayed diagnosis and care for patients with skin cancer.6 however, there remains limited data on the effect of these delays on skin cancer surgery outcomes, including stage of surgery and tumor size. to fill this gap, additional studies are warranted to determine the impact of the covid-19 pandemic on mohs micrographic surgery (mms) outcomes. the aim of this single center retrospective study was to determine changes in skin cancers treated with mms at a large, u.s. medical center in the context of evolving covid-19 pandemic restrictions over the course of several months. mms case logs identified patients treated with mms for skin cancer from march– september 2020 and march–september 2019. inclusion criteria included a diagnosis of skin cancer treated with mms. medical records were accessed using the electronic medical record. all pertinent patient and pathologic characteristics were documented. statistical analysis included kruskal-wallis, unpaired t-tests, and chi-square tests. this study included 1150 patients treated for 1307 tumors. the majority of patients were non-hispanic (79%), white (89%) and male (73%). the most common tumor was basal cell carcinoma (bcc) (43%), followed by squamous cell carcinoma (34%). 536 patients treated with mms during the study period in 2020 were compared to 614 seen in 2019 (table 1). age, gender, and race/ethnicity of patients were comparable between both groups, as was type of tumor being treated. patients treated in 2020 were strikingly more likely to be immunosuppressed (34% versus 13%, p< 0.0001), and trended towards having larger tumors, both factors likely impacting providers’ decisions to treat, as these features could indicate more aggressive skin cancers. patients seen in 2020 also had a greater difference between pre-operative tumor size and post-operative defect size, skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 404 table 1. comparison of patient demographic and clinical characteristics. table 1 depicts demographic and clinical characteristics of patients seen in 2019 compared to those seen in 2020. patients seen in 2020 were much more likely to have recurrent tumors, were strikingly more likely to be immunosuppressed, had a greater difference in pre and post-operative tumor size, and had an increased number of stages required for treatment. 2019 2020 p-value number of patients 614 536 number of tumors 698 609 age, median (iqr) 73 (66-79) 72 (64-79) nsa age, mean (sd) 72 (11) 71 (11) gender, n (%) nsb male 441 (72%) 399 (74%) female 173 (28%) 137 (26%) ethnicity, n (%) nsc non-hispanic 486 (79%) 432 (81%) hispanic 22 (4%) 29 (5%) unknown 106 (17%) 75 (14%) race, n (%) nsc white 556 (91%) 481 (90%) asian 2 (0%) 1 (0%) native american 2 (0%) 2 (0%) other/unknown 54 (9%) 52 (10%) immunosuppression, n (%) 80 (13%) 180 (34%) <0.0001b type of tumor, n (%) nsc bcc 321 (46%) 242 (40%) scc 229 (33%) 213 (35%) sccis 102 (15%) 112 (18%) mis 34 (5%) 33 (5%) ka 10 (1%) 6 (1%) other 2 (0%) 3 (0%) pre-operative tumor size, cm2, mean (sd) 1.70 (2.58) 1.72 (3.72) nsa post-operative defect size, cm2, mean (sd) 4.91 (6.08) 5.47 (8.1) nsa difference in pre/post-operative size, cm2, mean (sd) 3.21 (4.19) 3.75 (5.22) 0.03a number of stages, n (%) 0.03c 1 360 (52%) 297 (49%) 2 271 (39%) 228 (35%) 3 51 (7%) 55 (9%) 4 14 (2%) 17 (3%) 5+ 2 (0%) 11 (2%) number of stages, mean (sd) 1.61 (0.74) 1.73 (0.95) 0.01a type of repair, n (%) nsc simple closure 471 (77%) 444 (81%) second intention 151 (25%) 126 (21%) primary closure 320 (52%) 318 (58%) advanced repair 140 (23%) 104 (19%) advancement flap 38 (6%) 44 (8%) transposition flap 7 (1%) 13 (2%) rotation flap 31 (6%) 19 (3%) full thickness skin graft 26 (4%) 15 (3%) xenograft 9 (1%) 3 (1%) other (combination) 29 (4%) 10 (2%) referral to other specialist for repair, n (%) 87 (12%) 61 (10%) tumor status, n (%) 0.02b primary 682 (98%) 605 (99%) recurrent 26(2%) 4 (1%) abbreviations: ns: non-significant; iqr: interquartile range; sd: standard deviation; bcc: basal cell carcinoma, scc: squamous cell carcinoma; sccis: squamous cell carcinoma in situ; mis: melanoma in situ; ka: keratoacanthoma; cm: centimeter avalues computed with kruskal-wallis test bvalues computed with fischer’s exact test cvalues computed with chi-square test skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 405 (3.75 centimeters squared (cm2) versus 3.21cm2, p=0.03), and required more mms stages (mean 1.73 versus 1.61 stages in 2019, p=0.01, with a higher proportion of patients requiring three or more stages in 2020, p=0.03), suggesting an increase in subclinical spread of tumors potentially due to delay in presentation and subsequent treatment. however, patients seen in 2020 and 2019 had equivalent rates of advanced reconstruction such as flaps or grafts compared to primary closure or second intention. the covid-19 pandemic brought a significant disruption in non-emergent procedures, not only through governmental restrictions but also through changes in patient behavior. with covid-19-related changes and restrictions, patients presented with larger tumors and required more mms stages. treatment of high-risk, immunosuppressed patients was prioritized, and low-risk patients may have delayed treatment due to the pandemic. limitations of this study include that it is a single-center study at a tertiary referral center, potentially leading to overrepresentations of more severe presentations and its limited longterm outcome data. future analysis will be required to see long-term effects on skin cancer outcomes in subsequent years. providers should be aware of the potential effects of the covid-19 pandemic on skin cancer surgery and outcomes, with potential associated morbidity and mortality, in the context of preparation for long-term postpandemic sequelae, and additionally in preparation for any future large-scale pandemics or care interruptions. conflict of interest disclosures: none funding: none corresponding author: divya srivastava, md 5939 harry hines boulevard pob2, suite 400 phone: 214-645-8950 divya.srivastava@utsouthwestern.edu references: 1. nolan gs, dunne ja, kiely al, et al. the effect of the covid-19 pandemic on skin cancer surgery in the united kingdom: a national, multi-centre, prospective cohort study and survey of plastic surgeons. bjs (british journal of surgery). 2020;107(12):e598-e600. 2. geskin lj, trager mh, aasi sz, et al. perspectives on the recommendations for skin cancer management during the covid-19 pandemic. j am acad dermatol. 2020;83(1):295296. 3. earnshaw ch, hunter hja, mcmullen e, griffiths cem, warren rb. reduction in skin cancer diagnosis, and overall cancer referrals, during the covid-19 pandemic. br j dermatol. 2020;183(4):792-794. 4. andrew tw, alrawi m, lovat p. reduction in skin cancer diagnoses in the uk during the covid-19 pandemic. clin exp dermatol. 2021;46(1):145146. 5. capitelli-mcmahon h, hurley a, pinder r, matteucci p, totty j. characterising nonmelanoma skin cancer undergoing surgical management during the covid-19 pandemic. journal of plastic, reconstructive & aesthetic surgery : jpras. 2020:s1748-6815(1720)3053930538. 6. marson jw, maner bs, harding tp, et al. the magnitude of covid-19's effect on the timely management of melanoma and nonmelanoma skin cancers. j am acad dermatol. 2021;84(4):1100-1103. skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 274 research letter smoke evacuation in dermatology: a national cross-sectional analysis examining the behaviors and perceptions of dermatologists and dermatologic surgeons perry b. hooper, md1, samantha p. holmes, bs1, syril keena t. que, md, mph1 1indiana university school of medicine, department of dermatology, indianapolis, in surgical smoke is an occupational hazard in surgical and cosmetic dermatology. one gram of tissue vaporized by carbon dioxide (co2) laser and one gram of electrocauterized tissue contain the mutagenic potential of six and three unfiltered cigarettes, respectively.1 additionally, there have been several studies proving transmissibility of human papillomavirus (hpv) in the smoke plume,2,3 with several studies suggesting transmissibility of other viruses and bacteria.3,4 proper utilization of smoke protection is essential to mitigate the infectious, mutagenic, and direct physical hazards encountered over decades of practice. our aim is to elucidate the causes abstract background: despite associated hazards of surgical smoke, there is limited data regarding smoke evacuation practices among dermatologists. such information is especially relevant at this time as dermatologic procedures often involve exposure to aerosolized particles and known carcinogens. objective: to examine the barriers underlying historically low utilization of smoke protection among dermatologists methods: a survey was sent to dermatologists through the association of professors of dermatology (apd) list-serv and a cross-sectional analysis of responses was performed. results: a total of 85 dermatologists responded. twenty-four (28.2%) reported use of smoke evacuators during > 50% of dermatologic procedures. the odds of using smoke evacuation was 2.8 times higher in dermatologists with 10 or more years of experience (95% ci, 1.1-7.5; p=0.0358). the most commonly reported barriers to smoke evacuation were limited staffing (63.5%) and set-up time (61.2%). sixty-seven (78.8%) respondents reported that a hands-free evacuator could potentially increase the use of smoke evacuation in their practices. limitations: survey sent on academic listserv with relatively small sample size and limited generalizability. conclusions: smoke evacuation remains low among dermatologists despite the risks. identifying reasons for low utilization and receptiveness to potential solutions is necessary to improve safety practices relating to smoke evacuation. introduction skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 275 behind historically low utilization of protective devices and provide potential solutions. a survey was sent to dermatologists through the association of professors of dermatology (apd) list-serv and crosssectional analysis of responses was performed. a total of 85 dermatologists responded. table i dichotomizes “smoke evacuator use” as “infrequent use” (50% or less) versus “frequent use” (51% or more). the odds of using smoke evacuation was 2.8 times higher in dermatologists with 10 or more years of experience (95% ci, 1.1-7.5; p=0.0358). of the dermatologists using smoke evacuation frequently, 18 (75.0%) performed more than 100 surgeries per year versus 6 (25.0%) who performed less (p=0.0573). other variables such as gender, age, and practice setting did not significantly affect whether smoke evacuation was used frequently. the most commonly reported responses as to why smoke evacuators are not used were limited staffing (63.5 %) and set-up time of evacuators (61.2%) (table ii). regarding potential solutions to increase the use of smoke evacuators, the most common response at 78.8% was use of a hands-free surgical smoke evacuator followed by “education regarding risks associated with surgical smoke” at 70.6% (table ii). the results reflect those of previous publications showing low utilization of protective devices.1 71.8% reported “infrequent use” (50% or less) of surgical smoke evacuators. there appears to be more frequent utilization of smoke evacuation among dermatologists with more years of experience and those with higher case volumes and supporting staff. this survey directly addresses barriers to smoke evacuator use by asking dermatologists, in their opinion, why smoke evacuation is not always used. the most common reported barrier was availability of supporting staff, followed by set-up required to use a smoke evacuator. seventy-eight percent of dermatologists respond that the availability of a hands-free surgical smoke evacuator would facilitate the implementation of smoke evacuation in clinic. a potential solution to this issue is addressed in a recently published, handsfree setup for the smoke evacuator.5 furthermore, over half of respondents cite lack of education regarding associated hazards of surgical smoke as contributing to lack of protection, and 70.6% believe that further education regarding risks associated with surgical smoke would increase utilization of smoke evacuators. surgical smoke produced during dermatologic procedures has been shown to contain multiple hazardous materials. nevertheless, low compliance with smoke evacuators remains a prevalent issue. identifying reasons for low compliance will aid in the development of solutions that will increase smoke evacuator use among methods results discussion conclusion skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 276 table i. characteristics of the study population demographic characteristics *infrequent use of smoke evacuators (n= 61), no. (%) **frequent use of smoke evacuators (n=24), no. (%) p-value gender 0.832 male 24 (40.0) 9 (37.50) female 36 (60.0) 15 (62.50) age, median (range) 38 (26-69) 42 (29-67) 0.433 geography 0.0524 midwest 25 (41.0) 9 (37.5) northeast 12 (19.7) 4 (16.7) southeast 17 (27.9) 2 (8.3) west 5 (8.2) 7 (29.2) southwest 2 (3.3) 2 (8.3) practice setting 0.735 academic 54 (88.5) 22 (91.7) private practice 5 (8.2) 1 (4.2) multi-specialty 1 (1.6) 0 (0) veterans affairs hospital 1 (1.6) 1 (4.2) experience: number of years in dermatology practice more than 10 years 16 (26.2) 12 (50.0) 0.0358 less than 10 years 45 (73.8) 12 (50.0) caseload: number of dermatologic surgeries per year more than 100 cases 32 (52.5) 18 (75.0) 0.0573 less than 100 cases 29 (47.5) 6 (25.0) no. of staff available to assist during dermatologic procedures, median (range) 3.0 (0-30) 3.0 (1-50) 0.1 prior training (dermatology residency and/or fellowship) included use of smoke evacuator yes 17 (27.9) 9 (37.5) 0.386 no 44 (72.1) 15 (62.5) *“infrequent use” of smoke evacuators is defined as “use of smoke evacuator during 50% or less of cases generating surgical smoke”. **“frequent use” of smoke evacuators is defined as “use of smoke evacuator during more than 50% of cases generating surgical smoke”. table ii. barriers to the use of smoke evacuation and proposed solutions reason why smoke evacuation is not commonly used no. of respondents (% total)* proposed solutions to facilitate smoke evacuator use no. of respondents (% total)* staffing (i.e. operating alone or requiring both assistant's hands) 54 (63.5) use of a hands-free surgical smoke evacuator 67 (78.8) set-up time of evacuators 52 (61.2) education regarding risks associated with surgical smoke 60 (70.6) cost associated with smoke evacuators 44 (51.8) increase n95 mask availability 17 (20) lack of training regarding 38 (44.7) other 12 (14) skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 277 surgical smoke and smoke evacuators different form of smoke protection used (i.e. n95 mask) 5 (5.9) other 9 (10.6) *respondents were asked to select all choices that applied. percentages will not add up to 100%. dermatologists and mitigate associated risks of smoke exposure. irb approval status: exempted from review by indiana university human research protection program office conflict of interest disclosures: none funding: none corresponding author: perry hooper, md iu department of dermatology 545 barnhill drive emerson hall 139 indianapolis, in 46202 phone: 270-210-0911 email: pbhooper@iu.edu references: 1. yoshifumi, tomita, et al. “mutagenicity of smoke condensates induced by co2-laser irradiation and electrocauterization.” mutation research/genetic toxicology, vol. 89, no. 2, 1981, pp. 145–149., doi:10.1016/01651218(81)90120-8. 2. georgesen, corey, and shari r. lipner. “surgical smoke: risk assessment and mitigation strategies.” journal of the american academy of dermatology, vol. 79, no. 4, 2018, pp. 746–755., doi:10.1016/j.jaad.2018.06.003. 3. capizzi, peter j., et al. “microbiologic activity in laser resurfacing plume and debris.” lasers in surgery and medicine, vol. 23, no. 3, 1998, pp. 172–174., doi:10.1002/(sici)10969101(1998)23:33.0.co;2-m. 4. baggish, michael s., et al. “presence of human immunodeficiency virus dna in laser smoke.” lasers in surgery and medicine, vol. 11, no. 3, 1991, pp. 197–203., doi:10.1002/lsm.1900110302. 5. hooper, p. b., criscillies, k., & que, s. k. (2020). smoke evacuation: a novel solution in a busy clinical environment. journal of the american academy of dermatology. doi:10.1016/j.jaad.2020.05.139 mailto:pbhooper@iu.edu skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 85 brief articles histopathologic discordance in melanoma can have substantial impacts on patient care alex glazer, md1, clay j cockerell, md2 1department of dermatology, university of arizona, tucson, az 2cockerell dermatopathology, dallas, tx cutaneous melanoma (cm) is a significant and growing health concern in the united states. american joint committee on cancer (ajcc) staging is commonly used to estimate prognosis for patients based on breslow thickness, presence or absence of ulceration, sentinel lymph node (sln) status (where appropriate), and nodal tumor burden. mitotic rate was previously included in the 7th edition of ajcc substaging for thin melanomas, and is still considered by the national comprehensive cancer network as an adverse feature to consider discussion of sln biopsy (slnb) for t1a melanomas. while increasing stage is generally associated with poorer prognosis, there are limitations to its prognostic accuracy such that i) a substantial number of melanomarelated deaths are in patients diagnosed with early stage disease, ii) as many as two-thirds of patients who die from melanoma are slnnegative, and iii) heterogeneity of risk exists within each stage so that some earlier stages (i.e. stage iic) may portend a worse prognosis than that of nodal metastatic disease (i.e. stage iiia). one possibility to account for such limitations is the inherent subjectivity of traditional staging criteria, as well as other histopathologic features used in the clinical setting. considerable inter-observer variability has been reported for some of the histopathologic features used in staging and collected as part of pathology reports. while recommended guidelines for sentinel lymph node biopsy, follow-up, and surveillance for cutaneous melanoma are based upon clinicopathologic staging. in effect, the accuracy of melanoma staging to estimate metastatic risk is critical to subsequent care, neither undertreating or over-treating the patient based on their tumor. traditional staging continues to evolve based on additional data regarding clinicopathologic features and clinical outcomes. however, such features are subject to inter-observer variability, which puts a limit on their ability to improve prognostication. reported discordance rates between initial and subsequent pathology review consistently impact both staging and disease management. newer molecular techniques, such as gene expression profiling, can be used to help define the biology of the primary melanoma tumor and the best course of action after definitive surgical treatment. abstract introduction skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 86 overall inter-observer concordance of breslow thickness is higher than that reported for other features, such as ulceration or mitotic rate, its accuracy and interpretation can be impeded by regression and transection at the lesion base. discrepancies in measuring and reporting histopathologic features can impact melanoma diagnosis and prognostic staging with subsequent effects on definitive surgery, follow-up care and surveillance, sln biopsy (slnb) decisions, and treatment eligibility. as summarized in table 1, several studies have evaluated the concordance between pathology reports from referring centers that underwent re-review at academic referral centers1-5. while it should be noted that these studies evaluated concordance under previous versions of ajcc staging, the histopathologic features they considered are still recommended as additional factors driving clinical care under the current ajcc edition. a single-center study of 420 cases of in situ and thin melanomas that underwent standard re-review upon referral to moffitt cancer center found 24% discordance in pathologic tumor staging, which led to changes in recommended surgical margins for 12% and slnb for 16%2. notably, 76% of these referrals were originally evaluated by dermatopathologists, suggesting discordance exists even among those with specialized training. similarly, of 588 cases that underwent routine re-evaluation upon referral to emory university, 19% of cases had a change in pathologic staging (17% change in clinical stage), resulting in a change in slnb recommendation for 8% and follow-up for 5% based on national guidelines1. there was 66% discordance in breslow thickness alone with an average difference of 0.38 mm, but the differences in discordant measurements were not numerically statistically significant. a large study of cases referred to the melanoma institute of australia (mia) found 19% discordance in t stage among 3,620 cases with an agreed-upon diagnosis of invasive melanoma6. of 4,759 cases of in situ and invasive melanoma, changes in excision margins were recommended in 11% of cases after mia review. of 4,719 cases with adequate pathology reporting to make recommendations on sln biopsy, 8.6% underwent a change in slnb recommendation after mia review, including both patients for whom slnb would and would not have been recommended. changes in slnb results have also been reported after review of the same sln pathology slides of melanoma cases referred to the university of michigan3. thirteen out of 167 (8%) sln cases had discordant interpretations between the original pathology review and subsequent review at the university of michigan. it is possible that a lack of expert review prior to referral contributed to these discrepancies, as only 3 out of the 13 discordant cases were initially reviewed by dermatopathologists. five of the 13 discordant cases were re-diagnosed as sln negative, permitting the majority of these patients avoidance of completion lymph node dissection (clnd), and one patient discontinued interferon therapy as a result of down-staging. eight of the discrepant cases were upstaged to sln positive; two of these patients had additional nodal disease upon clnd and subsequently developed distant metastatic disease, from which one patient died. while numerous studies have shown that breslow thickness, ulceration, sln status, and other clinicopathologic features have significant prognostic value in melanoma, the reported studies skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 87 table 1. summary of reported histopathologic discordance and changes in recommended management. study design referral center; number of cases and type; years evaluated discordance in staging % (n/total) change in patient care recommendations (%) santillan et al. j clin oncol 2010; 28(3): 481-6 moffitt cancer center; 420 in situ and invasive melanoma cases; 20062009 24% (97/420) surgical margins: 12% (52/420) slnb: 16% (67/420) patrawala et al. j am acad derm 2016; 74(1):75-80 emory university hospital; 488 in situ and invasive melanoma cases; 2009-2014 19% (114/598; pathologic stage) 17% (101/598; clinical stage) surgical margins: 10% (58/588) slnb: 8% (45/588) follow-up: 5% (29/588) niebling et al. ann surg onc 2014; 21:2245-51 melanoma institute australia; 5011 consecutive in situ and invasive melanoma cases; 2002-2011 22% (945/4269; melanoma t stage) 20% (712/3620; invasive melanoma t stage) surgical margins: 11% (531/4759) slnb: 9% (407/4719) dandekar et al. ann surg onc 2014; 21:3406-11 university of michigan; 167 slns; 2006-2009 8% (13/167) sln+ to sln-: 3% (5/167) slnto sln+: 5% (8/167) slnb: 8% (13/167) monshizadeh et al. pathology 2012; 44(5): 441-7 western australian melanoma advisory service; 721 cases of in situ and invasive melanoma cases; 20002009 18% (n/r; pathologic stage) 16% (n/r; clinical stage) n/r murali et al. ann surg 2009; 249(4):641-7 sydney melanoma unit; 912 cases; 2-year study period (2002 ajcc staging) 3.8% (pathologic stage i-ii) 17.7% (t stage) 16.3% (ajcc substage) n/r n/r: not reported sln: sentinel lymph node; slnb: sentinel lymph node biopsy skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 88 subjectivity of histopathologic evaluation can have serious implications for melanoma patient care. national guidelines make recommendations based on ajcc stage and substage for decision-making on slnb, frequency of follow-up visits, surveillance imaging, and adjuvant therapy. therefore, pathologic assessment plays a critical role in driving management decisions for melanoma patients. in several cancers, molecular testing through gene expression profiling has been developed and implemented clinically as an additional, objective tool for use in conjunction with traditional staging methods to guide informed and individualized decisions on disease management. in cutaneous melanoma, a 31-gene expression profile (31-gep) test has been well-validated for its prognostic accuracy7-9. it has demonstrated a high degree of technical reliability, with 99% inter-assay and 100% intra-assay concordance in classifying melanomas as low (class 1) or high (class 2) risk for metastasis10. the 31-gep test result can be used to enhance the sensitivity of traditional staging for the identification of high-risk patients, providing additional assurance of appropriate risk stratification and subsequent development of optimal individualized management plans11,12. additionally, in melanoma cases with equivocal histopathology for staging, such as those described in the literature summarized herein (table 1), the 31-gep test also has clinical value in objectively interrogating tumor biology at the molecular level. as recognized by ajcc, melanoma staging, just as it has in the past, will continue to change as contemporary data supports additional prognostic features. in light of the studies summarized here, additional factors, including molecular analysis, could improve the reliability of staging and positively influence patient care by facilitating accurate and objective assessment of the tumor and its biological potential for metastasis. conflict of interest disclosures: ag participated in a research fellowship that was partially funded by castle biosciences, inc. cjc has served as a consultant and speaker for castle biosciences, inc. editorial assistance was provided by kristen plasseraud, phd, an employee and options holder of castle biosciences, inc.. funding: none. corresponding author: alex glazer, md university of arizona tucson, az alexglazer@gmail.com references: 1. patrawala s, maley a, greskovich c, et al. discordance of histopathologic parameters in cutaneous melanoma: clinical implications. journal of the american academy of dermatology. 2016;74(1):75-80. 2. santillan aa, messina jl, marzban ss, crespo g, sondak vk, zager js. pathology review of thin melanoma and melanoma in situ in a multidisciplinary melanoma clinic: impact on treatment decisions. journal of clinical oncology : official journal of the american society of clinical oncology. 2010;28(3):481-486. 3. dandekar m, lowe l, fullen dr, et al. discordance in histopathologic evaluation of melanoma sentinel lymph node biopsy with clinical follow-up: results from a prospectively collected database. annals of surgical oncology. 2014;21(11):3406-3411. 4. monshizadeh l, hanikeri m, beer tw, heenan pj. a critical review of melanoma pathology reports for patients referred to the western discussion skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 89 australian melanoma advisory service. pathology. 2012;44(5):441-447. 5. murali r, hughes mt, fitzgerald p, thompson jf, scolyer ra. interobserver variation in the histopathologic reporting of key prognostic parameters, particularly clark level, affects pathologic staging of primary cutaneous melanoma. annals of surgery. 2009;249(4):641-647. 6. niebling mg, haydu le, karim rz, thompson jf, scolyer ra. pathology review significantly affects diagnosis and treatment of melanoma patients: an analysis of 5011 patients treated at a melanoma treatment center. annals of surgical oncology. 2014;21(7):22452251. 7. gastman br, gerami p, kurley sj, cook rw, leachman s, vetto jt. identification of patients at risk for metastasis using a prognostic 31-gene expression profile in subpopulations of melanoma patients with favorable outcomes by standard criteria. journal of the american academy of dermatology. 2018;in press. 8. hsueh ec, debloom jr, lee j, et al. interim analysis of survival in a prospective, multi-center registry cohort of cutaneous melanoma tested with a prognostic 31-gene expression profile test. journal of hematology & oncology. 2017;10(1):152. 9. greenhaw bn, zitelli ja, brodland dg. estimation of prognosis in invasive cutaneous melanoma: an independent study of the accuracy of a gene expression profile test. dermatologic surgery : official publication for american society for dermatologic surgery [et al]. 2018. 10. cook rw, middlebrook b, wilkinson j, et al. analytic validity of decisiondxmelanoma, a gene expression profile test for determining metastatic risk in melanoma patients. diagnostic pathology. 2018;13(1):13. 11. dillon ld, gadzia je, davidson rs, et al. prospective, multicenter clinical impact evaluation of a 31-gene expression profile test for management of melanoma patients. skin, the journal of cutaneous medicine. 2018;2(3):111-121. 12. schuitevoerder d, heath m, cook rw, et al. impact of gene expression profiling on decision-making in clinically node negative melanoma patients after surgical staging. journal of drugs in dermatology : jdd. 2018;17(2):196199. 1department of dermatology, university of arizona, tucson, az 1department of dermatology, university of arizona, tucson, az 2cockerell dermatopathology, dallas, tx 2cockerell dermatopathology, dallas, tx poster presented at the 2018 fall clinical dermatology conference, october 18–21, las vegas, nevada (encore of asco 2018 poster presentation). conclusions • final data from the cscc expansion cohorts of the phase 1 study show that cemiplimab demonstrated an acceptable risk/benefit profile with substantial antitumor activity as well as durable responses. • furthermore, these results showed that cscc tumors, whether distantly metastatic or locally and/or regionally advanced, are responsive to cemiplimab. • primary analysis of the phase 2 study (nct02760498) provides further evidence of substantial antitumor activity and durable response with cemiplimab treatment in advanced cscc. background • cemiplimab (regn2810) is a high-affinity, highly potent, human, hinge-stabilized igg4 monoclonal antibody, generated using velocimmune® technology,1,2 directed against programmed death-1 (pd-1) receptor blocking the interactions of pd-1 with pd-ligand 1 (pd-l1) and pd-l2.3 • in the dose escalation portion of the phase 1 study of cemiplimab, an acceptable safety profile with no dose-limiting toxicities was demonstrated in patients with advanced solid tumors.4 a deep and durable response was observed in a patient with advanced cutaneous squamous cell carcinoma (cscc).4 • cscc is the second most common cancer in the us after basal cell carcinoma, and represents 20–50% of skin cancers in the us.5,6 • although cscc has a surgical cure rate of >95%, an estimated 3,932–8,791 patients died from cscc in 2012 in the us.7,8 • there is no approved systemic therapy for patients with advanced cscc (locally advanced cscc that is no longer amenable to surgery or radiation therapy, and metastatic cscc). • preliminary analysis suggests a positive risk/benefit profile and antitumor activity with cemiplimab treatment in the phase 1 cscc expansion cohorts of the first-in-human study.9 • we now report mature final data from the cscc expansion cohorts of the phase 1 study (nct02383212). objectives • the co-primary objectives of the cscc expansion cohorts were to: characterize the safety and tolerability of cemiplimab 3 mg/kg every two weeks (q2w) evaluate the efficacy of cemiplimab 3 mg/kg q2w by measuring overall response rate (orr). methods • adult patients with metastatic cscc or locally and/or regionally advanced cscc who were not candidates for surgery were enrolled (figure 1). • acceptable reasons for surgery to be deemed inappropriate for patients with locally/regionally advanced cscc were: recurrence of cscc after two or more surgical procedures and an expectation that curative resection would be unlikely, and/or; substantial morbidity or deformity anticipated from surgery. • key inclusion criteria included eastern cooperative oncology group (ecog) performance status of 0 or 1, adequate organ function, and at least one lesion measurable by response evaluation criteria in solid tumors (recist) version 1.1.10 references 1. macdonald le et al. proc natl acad sci. 2014;111:5147–5152. 2. murphy aj et al. proc natl acad sci. 2014;111:5153–5158. 3. burova e et al. mol cancer ther. 2017;16:861–870. 4. papadopoulos kp et al. j clin oncol. 2016;34(suppl abstr 3024). 5. rogers hw et al. jama dermatol. 2015;151:1081–1086. 6. que skt et al. j am acad dermatol. 2018;78:237–247. 7. kauvar an et al. dermatol surg. 2015;41:1214–1240. 8. karia ps et al. j am acad dermatol. 2013;68:957–966. 9. papadopoulos kp et al. j clin oncol. 2017;35(suppl abstr 9503). 10. eisenhauer ea et al. eur j cancer. 2009;45:228–247. acknowledgments we thank the patients, their families, and all investigators involved in this study. the study was funded by regeneron pharmaceuticals, inc., and sanofi. medical writing support and typesetting was provided by emmanuel ogunnowo of prime, knutsford, uk, funded by regeneron pharmaceuticals, inc., and sanofi. copies of this poster obtained through quick response (qr) code are for personal use only and may not be reproduced without permission from the author of this poster. phase 1 study of cemiplimab, a human monoclonal anti-pd-1, in patients with unresectable locally advanced or metastatic cutaneous squamous cell carcinoma (cscc): final efficacy and safety data taofeek k. owonikoko,1 kyriakos p. papadopoulos,2 melissa l. johnson,3 marta gil-martin,4 victor moreno,5 april k. salama,6 emiliano calvo,7 nelson s. yee,8 howard safran,9 raid aljumaily,10 daruka mahadevan,11 jiaxin niu,12 kosalai kal mohan,13 jingjin li,14 elizabeth stankevich,14 melissa mathias,13 israel lowy,13 matthew g. fury,14 hani m. babiker15 1department of hematology and medical oncology, winship cancer institute, emory university, atlanta, ga, usa; 2start, san antonio, tx, usa; 3sarah cannon research institute, nashville, tn, usa; 4institut català d’oncologia-idibell, l’hospitalet de llobregat, barcelona, spain; 5start madrid-fjd, hospital fundación jiménez díaz, madrid, spain; 6duke university, durham, nc, usa; 7start madrid, centro integral oncológico clara campal, madrid, spain; 8hematology/oncology division and penn state cancer institute, hershey, pa, usa; 9brown university, providence, ri, usa; 10oklahoma university medical center, oklahoma city, ok, usa; 11the university of arizona cancer center, tucson, az, usa. formerly of the university of tennessee health science center and west cancer center, memphis, tn, usa; 12department of medical oncology,banner md anderson cancer center, gilbert, az, usa; 13regeneron pharmaceuticals, inc., tarrytown, ny, usa; 14regeneron pharmaceuticals, inc., basking ridge, nj, usa; 15university of arizona cancer center, az, usa. • patients were excluded if they had any ongoing or recent (within 5 years) autoimmune disease requiring systemic immunosuppression; active brain metastases; or invasive malignancy within 5 years. • other selected exclusion criteria were treatment with immunosuppressive doses of steroids (>10 mg prednisone daily or equivalent); systemic antitumor treatment within 4 weeks of initial dose of cemiplimab; history of solid organ transplant; or primary tumors of lip or eyelid. • severity of adverse events was graded according to the national cancer institute common terminology criteria for adverse events (version 4.03). • the data cut-off date was october 02, 2017. results baseline characteristics, disposition, and treatment exposure • twenty-six patients (median age, 73 years; 10 metastatic and 16 locally/regionally advanced cscc) were enrolled. • patient baseline characteristics are summarized in table 1. • at the time of data cut-off (october 02, 2017), one patient (3.8%) was on treatment and 25 patients (96.2%) were off treatment. of the patients off treatment, 11 completed planned treatment and 14 have discontinued treatment (the most common reason for discontinuation was disease progression [n=7]). • the median number of administered doses of cemiplimab was 16 (range: 2–36) and the median duration of exposure was 36.0 weeks (range: 4.0–71.0). one patient had 71.0 weeks of continued cemiplimab exposure (beyond the planned 48-week treatment duration) as it was considered to be in the best interest of the patient. • the median duration of follow-up at the time of data cut-off was 11.0 months (range: 1.1–17.0). figure 4. time to and duration of response in responding patients plot shows time to response and duration of response in the 13 patients with confirmed partial response at the time of data cut-off. each horizontal bar represents one patient. metastatic cscc locally/regionally advanced cscc partial response stable disease progressive disease unable to evaluate ongoing study ongoing treatment month p at ie nt s w ith r es po ns e 0 2 4 6 8 10 12 14 16 18 20 treatment-emergent adverse events (teaes) • teaes of any grade, regardless of attribution, were reported in all patients (table 2). • investigator-assessed treatment-related teaes of any grade occurred in 15 patients (57.7%), with five patients (19.2%) experiencing the following six grade ≥3 treatment-related teaes: adrenal insufficiency, asthenia, increased alanine aminotransferase, increased aspartate aminotransferase, maculo-papular rash, and myalgia. • two patients (7.7%) discontinued treatment due to treatment-related teaes: an 85-year-old female developed grade 3 rash after three doses of cemiplimab; she completed post-treatment follow-up a 57-year-old male developed grade 2 muscular weakness after four doses of cemiplimab; patient continued treatment for an additional five doses before treatment was permanently discontinued due to this teae. • the most common investigator-assessed treatment-related teaes of any grade were fatigue (26.9%), and arthralgia, diarrhea, hypothyroidism, muscle weakness, and maculo-papular rash (each 7.7%). clinical efficacy • orr by independent central review was 50.0% (13/26 patients: 95% confidence interval [ci]: 29.9–70.1) (table 3). • durable disease control rate was 65.4% (95% ci: 44.3–82.8). table 1. patient demographics and baseline characteristics metastatic cscc (n=10) locally / regionally advanced cscc (n=16) total (n=26) median age (range), year 71 (55–85) 73 (56–88) 73 (55–88) ≥65 years old, n (%) 7 (70.0) 14 (87.5) 21 (80.8) male sex, n (%) 8 (80.0) 13 (81.3) 21 (80.8) ecog performance status score, n (%) 0 4 (40.0) 6 (37.5) 10 (38.5) 1 6 (60.0) 10 (62.5) 16 (61.5) primary cscc site, n (%) head/neck† 5 (50.0) 13 (81.2) 18 (69.2) extremity‡ 3 (30.0) 2 (12.5) 5 (19.2) trunk 1 (10.0) 1 (6.3) 2 (7.7) penis 1 (10.0) 0 1 (3.8) prior systemic therapy for cscc, n (%) 9 (90.0) 6 (37.5) 15 (57.7) prior radiotherapy for cscc, n (%) 6 (60.0) 14 (87.5) 20 (76.9) †includes ear and temple. ‡includes arms/hands and legs/feet. table 3. tumor response assessment by central review metastatic cscc (n=10) locally / regionally advanced cscc (n=16) total (n=26) best overall response, n (%) complete response 0 0 0 partial response 6 (60.0) 7 (43.8) 13 (50.0) stable disease 2 (20.0) 4 (25.0) 6 (23.1) non-complete response/ non-progressive disease† 1 (10.0) 0 1 (3.8) progressive disease 0 3 (18.8) 3 (11.5) not evaluable‡ 1 (10.0) 2 (12.5) 3 (11.5) overall response rate, % (95% ci) 60.0 (26.2–87.8) 43.8 (19.8–70.1) 50.0 (29.9–70.1) durable disease control rate, % (95% ci)§ 80.0 (44.4–97.5) 56.3 (29.9–80.2) 65.4 (44.3–82.8) median observed time to response, months (range)¶ 2.1 (1.7–3.6) 3.7 (1.7–7.3) 2.3 (1.7–7.3) †patients with non-measurable disease on central review of baseline imaging. ‡include missing and unknown tumor response. §defined as the proportion of patients without progressive disease for at least 105 days. ¶data shown are for patients with confirmed partial response as follows: metastatic cscc, n=6; locally/regionally advanced cscc, n=7; total, n=13. table 2. summary of teaes, regardless of attribution, in the combined cscc expansion cohorts teaes n=26 n (%) any grade grade ≥3 any 26 (100.0) 12 (46.2) serious 7 (26.9) 6 (23.1) led to discontinuation 2 (7.7) 0 with an outcome of death† 1 (3.8) 1 (3.8) occurred in at least four patients fatigue 7 (26.9) 0 constipation 4 (15.4) 0 decreased appetite 4 (15.4) 0 diarrhea 4 (15.4) 0 hypercalcemia 4 (15.4) 2 (7.7) hypophosphatemia 4 (15.4) 0 nausea 4 (15.4) 0 urinary tract infection 4 (15.4) 1 (3.8) †the fatal teae occurred in an 80-year-old man with baseline congestive heart failure and renal insufficiency who later had a teae of urinary tract infection and became anuric. the fatal renal failure was considered unrelated to study treatment. patients † b es t p er ce nt c ha ng e fr om b as el in e 100 80 60 40 20 0 –20 –40 –60 –80 –100 metastatic cscc locally/regionally advanced cscc partial response progressive disease stable disease figure 2. clinical activity of tumor response to cemiplimab in patients who underwent radiologic evaluation per independent central review plot shows the best percentage change in the sum of target lesion diameters from baseline for 22 patients from both cscc expansion cohorts who underwent radiologic evaluation per independent central review. lesion measurements after progression were excluded. the horizontal dashed lines indicate criteria for partial response (≥30% decrease in the sum of target lesion diameters) and progressive disease (≥20% increase in the target lesion diameters). the following four patients do not appear in the figure (but are included in the orr analysis [table 3], per intention-to-treat): one metastatic cscc patient with best response of non-complete response/ non-progressive disease and three patients (one metastatic and two locally/regionally advanced cscc) with no evaluable post-treatment tumor assessment. †considered partial response by independent central review of photographs, although recist measurements on radiology scans did not reach –30%. 100 80 60 40 20 0 –20 –40 –60 –80 –100 months p er ce nt c ha ng e in ta rg et le si on s fr om b as el in e 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 metastatic cscc locally/regionally advanced cscc figure 3. change in target lesion over time plot shows the percent change in target lesion diameters from baseline over time. patients shown in this figure are the same as those in figure 2. the horizontal dashed lines indicate criteria for partial response (≥30% decrease in the sum of target lesion diameters) and progressive disease (≥20% increase in the target lesion diameters). expansion cohort 7: patients with metastatic cscc expansion cohort 8: patients with locally and/or regionally advanced cscc tumor response assessment by an independent central review committee cemiplimab 3 mg/kg every 2 weeks, for up to 48 weeks response assessments every 8 weeks (recist 1.1) to determine overall response rate figure 1. study design: cscc expansion cohorts • rapid, deep, and durable target lesion reductions were observed in most patients who had at least one tumor assessment on treatment (figures 2–4). • median duration of response had not been reached at data cut-off. skin january 2018 volume 2 issue 1 copyright 2018 the national society for cutaneous medicine 44 short communications effects of imiquimod 5% cream in the prevention of excised keloid recurrence jennifer frias md a , raquel vargas md a , erika paez md a , marinna chopite md a , oscar reyes md a , natalia soucre md a , nicole swenson do b , brian berman md phd c a biomedicine institute, university of central venezuela b kcumb-gme consortium/adcs dermatology residency program c dermatology and cutaneous surgery, university of miami miller school of medicine, skin & cancer associates, center for clinical and cosmetic research the majority of keloids recur at the site of keloidectomy, and currently there are no medications approved to reduce keloid recurrence after excision. surgical excision of keloids has a reported 71% average weighted recurrence rate if preformed without adjuvant therapies. 1 treatment of surgical keloidectomy excision sites with topical imiquimod 5% cream for 8 weeks daily has been reported to have no recurrences of the keloids at the end of the relatively short, 24 week follow up period. 2 imiquimod has its immune modulatory effect partly due to induction of production of antifibrotic ifn-α, and tnf-α, interleukins 6 and 8, as well as recruitment and activation of cytokine producing plasmacytoid dendritic cells. 3 twenty five patients with at least one nonenlarging keloid were enrolled into this study, which was conducted at the biomedicine institute at the university of central venezuela. keloids at all anatomical sites between 5mm and 50mm in diameter without any treatment in the previous 3 months were eligible to be included in the study. a total of 41 keloids were shave excised tangentially along the long axis of the lesion, followed by curettage, hemostasis and a compression dressing. patients were instructed to wait 24 hours after the procedure to begin nightly applications of 5% imiquimod cream for 2 months. follow up visits occurred at 2 weeks after excision, and then every 4 weeks until 6 months postoperatively. 35 keloidectomy sites (20 auricular, 9 truncal, 2 suprapubic and 4 on extremities) were available for evaluation at the 6 month endpoint and all 20 auricular keloidectomy sites (16 lobe, 3 antihelix, 1 helix) were evaluated at 6 months and 5 years post keloidectomy. photographs were taken, introduction methods skin january 2018 volume 2 issue 1 copyright 2018 the national society for cutaneous medicine 45 adverse events were assessed, and the presence of a burning sensation at the application site was quantified using a visual analog scale at each visit. no systemic symptoms, such as fever or malaise, were reported by any subjects during the course of the study. all patients sensed burning at the imiquimod application site, in addition to pain, itching, inflammation, and wound crusting. three patients discontinued the study early due to application site adverse effects. at 6 months, all 9 of the excised keloids on the trunk and 4 keloids excised on the extremities had evidence of recurrence while of the 20 treated auricular keloids, only 3 had evidence of recurrence at 6 months and neither keloids in the suprapubic region had evidence of recurrence. the subset of 20 treated auricular keloids were followed up to 5 years after keloid treatment, with no additional recurrences were noted. photographs of earlobe keloid prior to, 2 months following, and 1 year following treatment are shown in figure 1. figure 1. photographs of earlobe keloid (a), post-shave excision and 2 months once-daily 5% imiquimod cream treatment (b), 5 year post-excision and treatment (c) the use of postoperative, topically applied, imiquimod following tangential shave removal, is a more limited and more effective intervention compared to the standard, complete excision of auricular and suprapubic keloids, with lower recurrence rates for up to 5 years. results conclusion a b c skin january 2018 volume 2 issue 1 copyright 2018 the national society for cutaneous medicine 46 conflict of interest disclosures: none. funding: none. corresponding author: brian berman, md, phd 2925 aventura boulevard, suite 205 aventura, fl 33180 305-933-6716 (office) 305-933-6720 (fax) bbmdphd@gmail.com references: 1. mustoe ta, cooter rd, gold mh, hobbs fd, ramelet aa, shakespeare pg et al. international advisory panel on scar management. international clinical recommendations on scar management. plast reconstr surg. 2002; 110: 560–571. 2. berman b, kaufman j. pilot study of the effect of postoperative imiquimod 5% cream on the recurrence rate of excised keloids. j am acad dermatol. 2002 oct;47(4 suppl):s209-11. 3. kim k, son d, kim j. radiation therapy following total keloidectomy: a retrospective study over 11 years. arch plast surg. 2015 sep;42(5):58895. neuropsychiatric adverse events in brodalumab psoriasis studies mark lebwohl,1 kim a. papp,2 jashin j. wu,3 andrew blauvelt,4 alan menter,5 shipra rastogi,6 radhakrishnan pillai,7 robert israel8 1icahn school of medicine at mount sinai, new york, ny, usa; 2probity medical research, waterloo, ontario, canada; 3kaiser permanente los angeles medical center, los angeles, ca, usa; 4oregon medical research center, portland, or, usa; 5baylor university medical center, dallas, tx, usa; 6ortho dermatologics, bridgewater, nj, usa; 7dow pharmaceutical sciences (a division of valeant pharmaceuticals north america llc), petaluma, ca, usa; 8valeant pharmaceuticals north america llc, bridgewater, nj, usa 2017 fall clinical dermatology conference® • october 12-15, 2017 • las vegas, nv introduction • psoriasis has profound psychosocial implications that can affect the ability of patients to socialize with family members, interact with coworkers, and make friends1 • psychiatric comorbidities, such as depression and anxiety, are common in patients with psoriasis2,3 • suicidal ideation has been reported in as many as 17.3% of patients with psoriasis compared with 8.3% of healthy controls4 • brodalumab is a monoclonal antibody that targets interleukin-17 (il-17) receptor a and is indicated for the treatment of psoriasis5 • brodalumab has demonstrated efficacy in the treatment of plaque psoriasis5,6 • reports of suicide in patients with psoriasis enrolled in clinical trials for brodalumab led to concerns that brodalumab may be linked to psychiatric adverse events (aes)6,7 objective • to assess psychiatric aes and improvements in depression and anxiety in patients with psoriasis treated with brodalumab in clinical trials methods clinical studies • efficacy and safety of brodalumab (140 or 210 mg every 2 weeks [q2w]) were investigated in one phase 2 trial and in three phase 3, multicenter, randomized trials of patients with moderate-to-severe plaque psoriasis (amagine-1/-2/-3)5,6 • in the phase 3 studies, more than 80% of patients were being treated with brodalumab 210 mg q2w by the end of the week 52 controlled period • there were no specific exclusion criteria for psychiatric disorders or substance abuse endpoints • the hospital anxiety and depression scale (hads), which determines anxiety and depression on a 21-point scale each, was measured in amagine-1 • the dermatology life quality index (dlqi) assesses the socio-psychological impact of the skin disease8 on patients’ lives and was measured in amagine-1/-2/-3 • data on psychiatric aes were pooled for all trials and were summarized as follow-up time–adjusted event rates – the follow-up time–adjusted event rate is the total number of events reported during the follow-up observation time divided by total patient-years of observation; this includes gaps and interruptions in exposure and time beyond the exposure period results • mean hads anxiety and depression scores significantly improved with brodalumab compared with placebo by 12 weeks (figure 1) • mean dlqi significantly improved with brodalumab compared with placebo by 12 weeks (figure 2) • rates of psychiatric adverse events were comparable between treatments at week 52 and did not increase with long-term treatment (table 1) • there were 22 suicidal ideations (follow-up time–adjusted rate, 0.24), 6 suicide attempts (0.07), 3 completed suicides (0.03), and 1 additional suicide adjudicated as indeterminate (table 2) • two suicidal ideation and behavior (sib) events (suicide attempts) were reported in 1 patient treated with brodalumab during the 12-week induction phase (0.03%; 1/3066) • follow-up time–adjusted rates of sib were greater in patients with a history of depression compared with those without (1.42 and 0.21 per 100 patient-years, respectively) • follow-up time–adjusted rates of sib were greater in patients with a history of suicidality compared with those without (3.21 and 0.20 per 100 patient-years, respectively) • of the 3 completed suicides, all patients were receiving brodalumab 210 mg, had baseline risk factors, and had demonstrated clinical responses (pasi ≥73; table 3) – time-to-event from first dose ranged from 140 to 845 days. follow-up time–adjusted sib rates through week 52 were lower in the brodalumab group compared with the ustekinumab group, with overlapping cis (0.20 [0.08, 0.41] vs 0.60 [0.12, 1.74]) – long-term rates of sib with brodalumab were slightly higher (0.37 [0.26, 0.52]) compared with those through week 52, with no increase in the completed suicide rate (0.04 [0.01, 0.11] vs 0.06 [0.01, 0.20]) table 2. integrated analysis of follow-up time–adjusted patient incidence rates of sib events through week 52 and in long-term follow-up 52-week poola long-term poolb ustekinumab (n=613; pt-yr = 503.6) n (r) [95% ci] brodalumab (n=4019; pt-yr = 3545.7) n (r) [95% ci] brodalumab (n=4464; pt-yr = 9161.8) n (r) [95% ci] suicidal ideation adverse event 1 (0.20) [0.01, 1.11] 3 (0.08) [0.02, 0.25] 22 (0.24) [0.15, 0.36] suicidal behavior adverse event completed suicidec intentional self-injury suicide attempt suicidal behavior 1 (0.20) [0.01, 1.11] 0 (0.00) [0.00, 0.73] 0 (0.00) [0.00, 0.73] 1 (0.20) [0.01, 1.11] 0 (0.00) [0.00, 0.73] 4 (0.11) [0.03, 0.29] 2 (0.06) [0.01, 0.20] 1 (0.03) [<0.01, 0.16] 1 (0.03) [<0.01, 0.16] 0 (0.00) [0.00, 0.10] 15 (0.16) [0.09, 0.27] 4 (0.04) [0.01, 1.11] 1 (0.01) [0.00, 0.06] 6 (0.07) [0.02, 0.14] 4 (0.04) [0.01, 1.11] overall suicidal ideation and behavior 2 (0.40) [0.05, 1.44] 7 (0.20) [0.08, 0.41] 34 (0.37) [0.26, 0.52] sib, suicidal ideation and behavior. acumulative events through the 52-week, controlled treatment period. bincludes events in the 52-week treatment period and the uncontrolled open-label extension. cincludes fatal event reported as intentional overdose that was adjudicated as indeterminate. table 1. incidence of psychiatric adverse events occurring in ≥0.1% of patients treated with brodalumab during the initial placebo-controlled study perioda preferred term, n (%) placebo (n=879) ustekinumab (n=613) brodalumabb (n=3066) psychiatric disorders soc 16 (1.8) 12 (2.0) 61 (2.0) insomnia 6 (0.7) 4 (0.7) 17 (0.6) depression 5 (0.6) 3 (0.5) 14 (0.5) anxiety 2 (0.2) 2 (0.3) 13 (0.4) libido decreased 0 (0) 0 (0) 5 (0.2) depressed mood 1 (0.1) 2 (0.3) 3 (0.1) mood swings 0 (0) 0 (0) 3 (0.1) stress 1 (0.1) 0 (0) 3 (0.1) soc, system organ class. aincludes data from the placebo-controlled phase 2 study, amagine-1, amagine-2, and amagine-3. ball brodalumab dose groups combined. table 3. summary of completed suicides (known and unknown cause) age, y/sex brodalumab dose clinical response (pasi score) clinical information 59/male 210 mg 100 • 329 days after first dose of brodalumab • history of financial stressors (lost disability due to brodalumab response and unable to find work) 39/male 210 mg 73 • 140 days after first dose of brodalumab • informed investigator he had legal difficulties and was likely to be incarcerated • family reported he killed himself, means unknown 56/male 210 mg 100 • 845 days after first dose of brodalumab • ongoing treatment for depression and anxiety • described recent stress and isolation due to relocation indeterminate case 56/male 210 mg 100 • history of depression; on antidepressant and benzodiazepine • 97 days after first dose of brodalumab • toxic levels of mixed opiates compatible with ingestion of poppy seed tea and methadone; therapeutic level of citalopram, elevated alprazolam, and alcohol • hads baseline depression and anxiety score decreased from 15 to 2 and 14 to 6, respectively, 2 weeks before the event • ruled indeterminate by c-casa adjudication c-casa, columbia classification algorithm of suicide assessment; hads, hospital anxiety and depression scale; pasi, psoriasis area and severity index. figure 1. shifts in hads severity for (a) depression and (b) anxiety at week 12 in patients who scored moderate or severe at baseline in the amagine-1 trial. improve improve to normal stay the same worsen pa tie nt s w ith s hi ft s in se ve ri ty g ro up s, % * 60 0 40 20 80 100 a b placebo brodalumab 140 mg q2w brodalumab 210 mg q2w depression pa tie nt s w ith s hi ft s in se ve ri ty g ro up s, % * 60 0 40 20 80 100 placebo brodalumab 140 mg q2w brodalumab 210 mg q2w anxiety hads, hospital anxiety and depression scale; q2w, every 2 weeks. shifts in hads severity at week 12 in patients who scored “moderate” or “severe” at baseline. *data are shown as observed; percentages do not add up to 100%. figure 2. dlqi 0/1 response rate at week 12 in patients from the amagine-1, -2, and -3 trials. placebo ustekinumab brodalumab 140 mg q2w brodalumab 210 mg q2w r es po ns e ra te , % 30 0 20 10 50 70 40 60 amagine-1 5% 5% 44% 44% 7% * 43% * 56% * 47% * 43% * 59% * 61% na amagine-2 amagine-3 dlqi 0/1 response to treatment dlqi, dermatology life quality index. dlqi response = score 0/1. *p<0.001 vs placebo. acknowledgments: this study was sponsored by ortho dermatologics. medical writing support was provided by medthink scicom and funded by ortho dermatologics. references: 1. krueger et al. arch dermatol. 2001;137:280-284. 2. dowlatshahi et al. j invest dermatol. 2014;134:1542-1551. 3. kurd et al. arch dermatol. 2010;146:891-895. 4. dalgard et al. j invest dermatol. 2015;135:984-991. 5. lebwohl et al. n engl j med. 2015;373:1318-1328. 6. papp et al. br j dermatol. 2016;175:273-286. 7. danesh and kimball. j am acad dermatol. 2016;74:190-192. 8. lewis and finlay. j investig dermatol symp proc. 2004;9:169-180. conclusions • mean hads anxiety and depression scores were reduced from baseline in patients with moderateto-severe plaque psoriasis receiving brodalumab • a higher patient satisfaction and quality of life was observed with brodalumab compared with placebo, as determined by dlqi response rate • rates of sib at week 52 in patients treated with brodalumab were similar to those treated with the active comparator ustekinumab, and sib rates did not increase with long-term treatment • no pattern emerged between timing of the events and the initiation or withdrawal of brodalumab • controlled data do not suggest a causal relationship between brodalumab treatment and sib © 2017. all rights reserved. 7407_fcdc sib encore poster_m1-2.indd 1 10/2/17 4:51 pm fc17postervaleantlebwohlneuropsychiatricadverseeffectspsoriasis.pdf powerpoint presentation sarecycline demonstrates narrow-spectrum antibacterial activity and anti-inflammatory effect in animal models christopher bunick1, james del rosso2, stephen tyring3, michael draper4, jodi l. johnson5, ayman grada6 1department of dermatology, yale university school of medicine, new haven, ct, usa, 2jdr dermatology research llc/thomas dermatology, las vegas and henderson, nevada, usa 3university of texas health science center, department of dermatology & center for clinical studies, houston, tx, usa, 4paratek pharmaceuticals, inc.(at the time of the study), boston, -massachusetts, usa, 5departments of dermatology and pathology, feinberg school of medicine, northwestern university, usa, 6r&d and medical affairs, almirall (us), exton, pennsylvania, usa poster accepted for winter clinical dermatology meeting 2021. introduction methods results table 1. efficacy of sarecycline and comparators against s. aureus and e. coli in mice results table 2. efficacy of sarecycline and doxycycline against s. aureus tissue infection results table 3. anti-inflammatory effect of sarecycline and comparators in rat footpad model antibacterial s. aureus rn450-1 e. coli pbs1478 agent mic (mg/ml) pd50 (mg/kg) mic (mg/ml) pd50 (mg/kg) sarecycline < 0.06 0.25 4 > 40 doxycycline < 0.06 0.3 0.5 5.72 minocycline < 0.06 0.03 1 6.95 murine systemic infection model at 48 h post-infection. agent mic (mg/ml) ed50 (mg/kg) sarecycline < 0.06 8.23 doxycycline < 0.06 8.31 ➢ sarecycline demonstrated in vivo efficacy against s. aureus but not e. coli in animal models of infection, in agreement with the narrower-spectrum of activity observed in in vitro studies. ➢ sarecycline showed anti-inflammatory effect comparable to doxycycline and minocycline in the rat footpad edema model. discussion compound mean % inflammation compared to untreated controls 150 mg/kg 100 mg/kg 75 mg/kg 50 mg/kg 25 mg/kg 10 mg/kg 5 mg/kg 1 mg/kg sarecycline 25.8 53.1 55.7 52 59 65.2 77.8 103.3 doxycycline 36 67.6 minocycline 20.5 53.9 32.9 47.2 carrageenan-induced rat footpad edema model ➢ sarecycline is the first narrow-spectrum tetracycline-class antibiotic to be developed for the treatment of acne vulgaris. ▪ sarecycline is an fda-approved tetracycline-class oral antibiotic specifically developed for the treatment of moderate-to-severe acne vulgaris. ▪ in vitro studies demonstrated a narrow-spectrum antibacterial activity, targeting clinically relevant gram-positive bacteria while showing reduced activity against gram-negative bacteria commonly found in the human gastrointestinal tract. ▪ here we report results of in vivo antibacterial and anti-inflammatory studies in mouse and rat models. in vivo antibacterial activity table 1. a murine systemic (intraperitoneal) infection model was utilized to assess the in vivo efficacies of sarecycline, doxycycline, and minocycline against s. aureus rn450-1 and e. coli pbs1478. table 2. a murine neutropenic thigh wound infection model was utilized to represent a tissue-based infection to assess the comparative efficacies of sarecycline and doxycycline against s. aureus rn450-1. anti-inflammatory effect in vivo table 3. to evaluate the anti-inflammatory effects of sarecycline, a carrageenaninduced rat footpad edema model was utilized. male, sprague dawley rats were intraperitoneally injected with saline, sarecycline, or a positive control (doxycycline or minocycline) and inflammation was determined as change in paw volume. percent inflammation was calculated as 100 x [(post paw volume at 3 hours – pre paw volume at 0 hours)/pre paw volume at 0 hours]. conclusions murine neutropenic thigh wound infection model to represent tissue-based infection with s. aureus rn450-1. references zhanel g, et al. microbiological profile of sarecycline, a novel targeted spectrum tetracycline for the treatment of acne vulgaris. antimicrob agents chemother: 2018 dec;63(1):e01297-18. carrageenan-induced rat footpad edema model experiments performed by paratek pharmaceuticals. data on file with almirall. ➢ the reduced activity of sarecycline against bacteria commonly found in the gut suggests reduced risk of antibiotic resistance within the gi tract microbiome. ➢ sarecycline proved effective against s. aureus (g+ bacteria) in both systemic and tissue-based infection models in mice. however, low efficacy was demonstrated vs. e.coli (genteric bacteria). ➢ the anti-inflammatory effect of sarecycline in rats is similar to doxycycline and minocycline, and in agreement with sarecycline being efficacious for inflammatory moderate-to-severe acne lesions in humans. mic – minimum inhibitory concentration; pd50 – protective dose required to achieve 50% survival mic – minimum inhibitory concentration; ed50 – effective dose required to achieve a 50%, or 2-log10, reduction in bacterial burden corresponding email:grada@bu.edu skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 122 rising derm stars® access to injectable biologic medications by medicare beneficiaries: geographic distribution of u.s. dermatologist prescribers jeffrey cohen, md1 1department of dermatology, new york university, new york, ny background/objectives: injectable biologics (ib) have emerged as some of the most effective therapies for inflammatory skin disease and this study sought to examine the distribution of u.s. ib-prescribing dermatologists. methods: this study used centers for medicare and medicaid services medicare provider utilization and payment data: part d for 2013-2015. primary outcome measures included the densities of dermatologists who prescribed ib (etanercept, adalimumab, ustekinumab, secukinumab) in each u.s. county for any indication, represented as the number of biologic-prescribers per 100,000 medicare part d beneficiaries. each county was assigned a nine-point rural-urban continuum code (rucc) based on size, degree of urbanization, and proximity to metropolitan areas. the proportion of counties in each rucc with a dermatologist who prescribes biologics was also explored. results: 2,992 dermatologists (26.3% of dermatologists) prescribed ib in this study. the national density of ib-prescribing dermatologists was 7.22. only 778 counties (24.8%) had at least one ib-prescribing dermatologist. the densities of ibprescribing dermatologists in metropolitan counties were 8.07-8.12. the densities of ibprescribing dermatologists were 4.55 and 6.51 for urban populations of greater than 20,000 people adjacent and non-adjacent to metropolitan areas, respectively. urban counties with populations between 2,50019,999 and adjacent to a metropolitan area had a density of 2.03 and urban counties with the same population and not adjacent to a metropolitan area had a density of 2.84. completely rural or urban counties with populations under 2,500 people had densities between 2.31-2.35. conclusion: there are disparities in the availability of ib-prescribing dermatologists across urban-rural geographic settings in the u.s. with greatest access in large urban areas and very limited access in more rural settings. skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 123 table 1: county characteristics for biologic-prescribing dermatologists (derms) by rural urban continuum code (rucc). density represented as the number of dermatologists per 100,000 medicare part d beneficiaries (mpdb). rucc description no. derms prescribin g biologics to mpdb no. mpdb density of derms prescribing biologics per 100,000 mpdb no. counti es no. counties without a derm prescribing biologics to mpdb % counties without a derm prescribing biologics to mpdb 1 counties in metropolitan areas of 1 million population or more 1665 20620651 8.07 431 193 44.8 2 counties in metropolitan areas of 250,000 to 1 million population 740 9111095 8.12 379 183 48.3 3 counties in metropolitan areas of fewer than 250,000 population 334 4120500 8.11 355 200 56.3 4 urban population of 20,000 or more, adjacent to a metropolitan area 99 2178029 4.55 214 149 69.6 5 urban population of 20,000 or more, not adjacent to a metropolitan area 45 691367 6.51 92 60 65.2 6 urban population of 2,500 to 19,999, adjacent to a metropolitan area 50 2465176 2.03 593 552 93.1 skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 124 7 urban population of 2,500 to 19,999, not adjacent to a metropolitan area 39 1373419 2.84 433 400 92.4 8 completely rural or less than 2,500 urban population, adjacent to a metropolitan area 9 382825 2.35 220 212 96.4 9 completely rural or less than 2,500 urban population, not adjacent to a metropolitan area 11 475060 2.32 424 414 97.6 total 2992 41418122 7.22 3141 2363 75.2 skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 125 references: 1. veilleux ms, shear nh. biologics in patients with skin diseases. j allergy clin immunol. 2017;139(5):1423-1430. 2. lebwohl mg, kavanaugh a, armstrong aw, et al. us perspectives in the management of psoriasis and psoriatic arthritis: patient and physician results from the population-based multinational assessment of psoriasis and psoriatic arthritis (mapp) survey. am j clin dermatol. 2016;17(1):87-97. 3. armstrong aw, koning jw, rowse s, et al. under-treatment of patients with moderate to severe psoriasis in the united states: analysis of medication usage with health plan data. dermatol ther (heidelb). 2017;7(1):97-109. 4. takeshita j, gelfand jm, li p, et al. psoriasis in the us medicare population: prevalence, treatment, and factors associated with biologic use. j invest dermatol. 2015;135(12):29552963. 5. ingram dd, franco sj. 2013 nchs urban-rural classification scheme for counties. vital health stat 2. 2014;(166)(166):1-73. skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 311 brief article true serum sickness, pearls for clinical diagnosis jack lee, md1, patrick c. carr, md1, barrett j. zlotoff, md1, darren j. guffey, md1 1department of dermatology, university of virginia, charlottesville, va a 28 year-old woman with type 1 diabetes and penicillin allergy was admitted for pancreatic transplant, complicated by graft failure on day 2 requiring graft pancreatectomy. she received 2 doses of anti-thymocyte globulin (atg) on day of transplant and briefly mycophenolate and tacrolimus. she was discharged on trimethoprim-sulfamethoxazole, linezolid, ciprofloxacin, metronidazole, fluconazole, and valacyclovir. nine days later she was readmitted for spiking fevers to 102.2f and severe myalgias and arthralgias rendering her nearly immobile. she had marked bilateral temporomandibular joint (tmj) pain that limited her speech and intake. intravenous antibiotics were initiated and a rash developed shortly after. examination was notable for a diffuse morbilliform exanthem featuring unusual serpiginous bands of erythema on the lateral aspects of the bilateral feet occurring at the margin of plantar skin (figure 1). her face was edematous. joint swelling and lymphadenopathy were difficult to evaluate due to habitus. infectious workup, blood counts, metabolic panel, creatinine kinase, and urinalysis were notable for elevated transminases that had been downtrending since her previous admission, and neutrophilia (table 1). skin biopsy showed mild vacuolar interface dermatitis. further labs revealed low ch50, c3, and c4 (table abstract background: true serum sickness is a type 3 hypersensitivity reaction against foreign antibodies, resulting in vasculitis and an acute clinical presentation. historically reported with anti-venin, currently anti-thymocyte globulin in the context of transplant rejection prophylaxis remains one of the most common causes. the classic clinical triad of fevers, arthralgias, and rash is not consistently present, and the rash is often difficult to distinguish from typical drug reactions. however, certain unique findings can assist with diagnosis. case presentation: we present a case of true serum sickness secondary to anti-thymocyte globulin featuring key exam and laboratory findings that enabled differentiation from other possible overlapping clinical entities, particularly drug reactions. conclusions: marked temporomandibular jaw pain is an important early clue to the diagnosis. linear serpiginous erythema along the plantar margin may be a specific feature when rash is present. to our knowledge, neither have been reported in similar clinical entities including serum-sickness-like reaction. serum complement levels and direct immunofluorescence (if skin biopsy done) are useful for distinguishing true serum sickness from primary differentials serum sickness-like reaction and drug rash with eosinophilia and systemic symptoms. case presentation skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 312 1). a diagnosis of true serum sickness (ss) secondary to atg was rendered. prednisone taper was initiated, and on follow-up 3 weeks later her symptoms had resolved. figure 1. clinical image demonstrating serpiginous bands of erythema along the plantar margin. atg persists as one of the most common causes of ss given its continued popularity in transplant rejection prophylaxis, and immunogenicity as a heterologous antibody derived from rabbits or horses. in a prospective cohort study of 240 renal transplant patients receiving atg, 7.5% developed ss.1 the pathomechanism involves a type 3 hypersensitivity with deposition of circulating antibody complexes, triggering complement consumption and vasculitis. this vasculitis produces the classic clinical triad of spiking fevers, debilitating musculoskeletal pain, and rash. an urticarial rash is classic, however morbilliform presentations are common. onset from exposure is 7-14 days, corresponding to time required to mount an antibody response. facial swelling, lymphadenopathy, and nephritis are additional common features. this pathomechanism is similar to how disease manifests in certain autoimmune conditions, such as nephritis in systemic lupus erythematosus. conceivably, autoimmune conditions such as in our patient may reflect a greater tendency to develop ss, and the literature is limited but suggestive. a retrospective study of reports of rituximab-induced ss in the french pharmacovigilance database found a higher incidence in patients being treated for autoimmune diseases (6.4 cases/105 doses) compared to those treated for hematologic malignancies (0.5 cases/105 doses), especially for lupus (48.6 cases/105 doses).2 interestingly, in a phase ii clinical trial of 58 patients receiving atg for treatment of type 1 diabetes, all patients localized to the treatment arm (38) developed ss.3 characteristic clinical findings in atgrelated ss and possibly ss in general include tmj pain as an early clue, and serpiginous bands of erythema along the palmar or plantar margins. in studies detailing localization of arthralgias, 5 of 5 atg-induced cases and 3 of 8 infliximabinduced cases reported jaw pain.4-6 in studies describing rashes in detail (all atg), palmoplantar bands were present in 29 of 39 (74%) patients.7,8 ss remains a clinical diagnosis and biopsies are generally not indicated, however transplant patients are exposed to multiple new medications and susceptible to many infections. thus, skin biopsies can be helpful to navigate a broadly overlapping differential. discussion skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 313 table 1. key laboratory investigations at time of admission complete blood count value reference range white blood cells 15.99 k/ul 4.00 – 11.00 k/ul neutrophils, absolute 15.17 k/ul 1.80 – 8.00 k/ul lymphocytes, absolute 0.27 k/ul 1.00 – 5.00 k/ul eosinophils, absolute 0.14 k/ul 0.00 – 0.60 k/ul hemoglobin 9.7 g/dl 12.0 – 16.0 g/dl platelets 217 k/ul 150 – 450 k/ul metabolic panel blood urea nitrogen 21 mmol/l 22 – 29 mmol/l creatinine 0.7 mg/dl 0.7 – 1.1 mg/dl glucose 166 mg/dl 74 – 99 mg/dl albumin 3.8 g/dl 3.2 – 5.2 g/dl total bilirubin 0.6 mg/dl 0.3-1.2 mg/dl alkaline phosphatase 122 u/l 40 – 150 u/l aspartate aminotransferase 41 u/l <35 u/l alanine aminotransferase 76 u/l <55 u/l inflammatory panel creatinine kinase 32 u/l 30-170 u/l c-reactive protein 21.7 mg/dl <0.5 mg/dl erythrocyte sedimentation rate 69 mm/h 0 – 30 mm/h ch50 complement 35 u/ml 42 – 95 u/ml c3 complement 77 mg/dl 83 – 193 mg/dl c4 complement 11 mg/dl 15 – 57 mg/dl anti-nuclear antibody negative negative rheumatoid factor 14.1 iu/ml <30.0 iu/ml ccp igg antibody 1.5 u/ml <3.0 u/ml infectious panel blood culture (x3) no growth no growth gastrointestinal pathogens pcr panel* none detected none detected respiratory pathogens pcr panel* none detected none detected urinalysis* all normal all normal urine culture no growth no growth covid-19 swab pcr none detected none detected cytomegalovirus viral load none detected none detected epstein-barr virus viral load none detected none detected human herpesvirus-6 pcr none detected none detected *gastrointestinal panel genera: campylobacter, plesiomonas, salmonella, vibrio, yersinia, e. coli, shigella, cryptosporidium, cyclospora, entamoeba, giardia, adenovirus, astrovirus, norovirus, rotavirus, sapovirus. respiratory panel genera; adenovirus, coronavirus, metapneumovirus, rhinovirus, influenza, parainfluenza, rsv, mycoplasma, chlamydia. urinalysis: glucose, protein, bilirubin, urobilinogen, ph, blood, ketone, nitrite, leukocyte esterase, opacity, color. despite the proposed pathomechanism, skin biopsies rarely show the specific finding of vasculitis. out of 18 collective skin biopsies reported in the literature (all atg), only one featured vasculitis.7,8 however, of 14 tissue samples that were also sent for direct immunofluorescence (dif), 10 (71%) showed immune deposits within blood vessels with varying combinations of iga/m/e and c3, but not igg.7,8 hence if a biopsy is being considered with ss on the skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 314 differential, particularly atg-related, an accompanying dif is recommended. serum sickness-like reaction (sslr) is distinct from ss but often confused with the latter due to overlapping clinical features and timing of onset. rather than an immune response against foreign antibodies, sslr is a drug reaction, often from antibiotic or antiepileptic exposure in pediatric patients. the exact pathomechanism is unknown, however immune complexes and vasculitis are absent, therefore hypocomplementemia and nephritis do not occur. also, to our knowledge, jaw pain and serpinginous bands along the volar margins have not been reported in sslr. both ss and sslr are self-limited once the causative agent is discontinued. in general there are no longterm sequelae. systemic steroids are sometimes indicated if severely symptomatic. a more serious entity with substantial clinical overlap is drug rash with eosinophilia and systemic symptoms (dress), a morbilliform drug eruption with the key feature of endorgan damage, most commonly of the kidneys and liver. eosinophilia is characteristic but often absent. fever, arthralgias, and lymphadenopathy are common, and facial edema is an important early clue. like ss, skin biopsies tend to be nonspecific. both entities can feature nephritis, leading to similar findings on urinalysis and renal function tests. in our patient, the distinguishing features were hypocomplementemia, impressive tmj pain, and peculiar serpiginous bands occurring at her plantar margins. we propose complement levels as an accessible and effective test in ruling out overlapping entities, including sslr and dress. c1q binding and raji cell assays for detecting immune complexes can be helpful, however these are not widely available. an elisa for anti-atg with 86% sensitivity, despite being a major diagnostic criterion for ss, suffers from significant interlaboratory variability and limited availability.9 hypocomplementemia is currently only a minor diagnostic criterion for ss, as levels do not precisely parallel clinical symptoms. however, earlier checks could be more helpful. on review of the literature, complement levels collectively obtained in 39 patients with atg-related ss showed 31 were low in either c3 or c4 (79%).1,4,5,8,10 the 8 cases with normal complement were drawn later (18-25 days after first atg dose) compared to cases with low complement (714 days), suggesting higher sensitivity when checked earlier. the largest prospective study followed 11 patients and found complement levels reached their nadir an average of 11 days after starting atg.8 compared with symptom onset averaging 9.5 days, this suggests complement levels are more useful when drawn closer to symptom onset. some patients had low complement at baseline, however onset of ss led to even further decreases.8 complement levels were also low in 3 of 3 rituximab-induced cases, checked at symptom onset 7-9 days after last infusion.11,12 in summary, we present a case of ss presenting with lesser-known but characteristic exam features of marked tmj pain (early clue), and serpiginous bands along the plantar margin. we recommend checking complement levels, ideally close to symptom onset, as a quick and effective method to distinguish from primary differentials sslr and dress. if skin conclusion skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 315 biopsy is done, we recommend including dif. conflict of interest disclosures: none funding: none corresponding author: jack lee, md box 800718 department of dermatology university of virginia charlottesville, virginia 22908-0718 phone: 434-924-5115 fax: 434-244-4504 email: jl4eg@virginia.edu references: 1. büchler m, hurault de ligny b, madec c, lebranchu y; french thymoglobuline pharmacovigilance study group. induction therapy by anti-thymocyte globulin (rabbit) in renal transplantation: a 1-yr follow-up of safety and efficacy. clin transplant. 2003 dec;17(6):539-45. doi: 10.1046/j.13990012.2003.00102.x. pmid: 14756271. 2. bayer g, agier ms, lioger b, lepelley m, zenut m, lanoue mc, maillot f, jonville-bera ap. rituximab-induced serum sickness is more frequent in autoimmune diseases as compared to hematological malignancies: a french nationwide study. eur j intern med. 2019 sep;67:59-64. doi: 10.1016/j.ejim.2019.06.009. epub 2019 jul 3. pmid: 31279430. 3. gitelman, s.e., gottlieb, p.a., felner, e.i. et al. antithymocyte globulin therapy for patients with recent-onset type 1 diabetes: 2 year results of a randomised trial. diabetologia 59, 1153–1161 (2016). https://doi.org/10.1007/s00125-016-39174 4. boothpur r, hardinger kl, skelton rm, lluka b, koch mj, miller bw, desai nm, brennan dc. serum sickness after treatment with rabbit antithymocyte globulin in kidney transplant recipients with previous rabbit exposure. am j kidney dis. 2010 jan;55(1):141-3. doi: 10.1053/j.ajkd.2009.06.017. epub 2009 jul 23. pmid: 19628314; pmcid: pmc2803326. 5. lundquist al, chari rs, wood jh, miller gg, schaefer hm, raiford ds, wright kj, gorden dl. serum sickness following rabbit antithymocyteglobulin induction in a liver transplant recipient: case report and literature review. liver transpl. 2007 may;13(5):647-50. doi: 10.1002/lt.21098. pmid: 17377915. 6. lees cw, ali ai, thompson ai, ho gt, forsythe ro, marquez l, cochrane cj, aitken s, fennell j, rogers p, shand ag, penman id, palmer kr, wilson dc, arnott id, satsangi j. the safety profile of anti-tumour necrosis factor therapy in inflammatory bowel disease in clinical practice: analysis of 620 patient-years follow-up. aliment pharmacol ther. 2009 feb 1;29(3):286-97. doi: 10.1111/j.1365-2036.2008.03882.x. pmid: 19132970. 7. bielory l, yancey kb, young ns, frank mm, lawley tj. cutaneous manifestations of serum sickness in patients receiving antithymocyte globulin. j am acad dermatol. 1985 sep;13(3):411-7. doi: 10.1016/s01909622(85)70182-x. pmid: 3877081. 8. lawley tj, bielory l, gascon p, yancey kb, young ns, frank mm. a study of human serum sickness. j invest dermatol. 1985 jul;85(1 suppl):129s-132s. doi: 10.1111/15231747.ep12275641. pmid: 3891879. 9. tatum ah, bollinger rr, sanfilippo f. rapid serologic diagnosis of serum sickness from antithymocyte globulin therapy using enzyme immunoassay. transplantation. 1984 dec;38(6):582-6. doi: 10.1097/00007890198412000-00006. pmid: 6334386. 10. snow mh, cannella ac, stevens rb, mikuls tr. presumptive serum sickness as a complication of rabbit-derived antithymocyte globulin immunosuppression. arthritis rheum. 2009 sep 15;61(9):1271-4. doi: 10.1002/art.24788. pmid: 19714613. 11. karmacharya p, poudel dr, pathak r, donato aa, ghimire s, giri s, aryal mr, bingham co 3rd. rituximab-induced serum sickness: a systematic review. semin arthritis rheum. 2015 dec;45(3):334-40. doi: 10.1016/j.semarthrit.2015.06.014. epub 2015 jun 26. pmid: 26199061. 12. sène d, ghillani-dalbin p, amoura z, musset l, cacoub p. rituximab may form a complex with igmkappa mixed cryoglobulin and induce severe systemic reactions in patients with hepatitis c virus-induced vasculitis. arthritis rheum. 2009 dec;60(12):3848-55. doi: 10.1002/art.25000. pmid: 19950292. skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 80 short communications pruritic rash and oral erosions during nivolumab treatment for melanoma shant tamazian, bs1, emily y. chu, md, phd1, cory l. simpson, md, phd1 1department of dermatology, perelman school of medicine, university of pennsylvania, philadelphia, pa to the editor: a 76-year-old man with a history of stage 3 melanoma treated with nivolumab presented with a persistent eruption of intensely pruritic papules on the trunk that started six months after initiating immunotherapy. he denied skin blistering. the patient also reported recurrent bloodfilled blisters in the mouth that ruptured to form painful erosions. physical examination revealed scattered erythematous papules without vesiculation on the back (figure 1a), excoriated papules on the chest (figure 1b), and several shallow erosions of the buccal mucosa (figure 1c). immunohistochemical (ihc) staining of the skin biopsy showed linear deposition of complement protein c3d along the dermal-epidermal junction (figure 2) and enzyme-linked immunosorbent assay (elisa) revealed anti-bp180 antibodies, confirming a diagnosis of bullous pemphigoid. bullous pemphigoid (bp) is a rare autoimmune skin disease that typically affects elderly patients. although bp is usually idiopathic, numerous medications have been reported as suspected causative agents. more recently, cases of bp have been associated with inhibitors of programmed cell death 1 (pd-1) receptor and its ligand (pd-l1)1, which are now widely used in the treatment of various cancers, including nivolumab for advanced melanoma. while intense pruritus and tense bullae are the typical skin findings in bp, patients can also present with non-blistering urticarial papules, as in this case (figure 1a). moreover, oral erosions are an underrecognized feature of bp despite their presence in approximately 17% of cases.2 bp is caused by auto-antibodies that bind to hemi-desmosomes, which adhere epidermal keratinocytes to the basement membrane zone (bmz); auto-antibody deposition results in an inflammatory infiltrate at the dermal-epidermal junction and subsequent subepidermal blistering. diagnosis of bp is confirmed by identifying auto-antibodies recognizing hemi-desmosome proteins (bp180 and/or bp230); circulating autoantibodies can be detected in the serum using elisa or indirect immunofluorescence while tissue-deposited auto-antibodies at the bmz can be visualized by direct immunofluorescence of unfixed peri-lesional skin or by ihc staining of fixed lesional tissue sections for complement protein c3d.3 treatment of idiopathic bp varies depending on illness severity and patient performance status, relying heavily on expert opinion due to the limited number of prospective randomized studies. while severe cases often require systemic corticosteroids, ultraskin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 81 figure 1. (a) scattered non-bullous erythematous papules were noted on the back. (b) excoriated papules were present on the chest. (c) shallow erosions were present on the buccal mucosa. figure 2. immunohistochemistry staining of a punch biopsy of lesional skin from the back showed linear deposition of complement protein c3d (red) along the dermal-epidermal junction (200x). potent topical corticosteroids and doxycycline4 are effective for treating bp without systemic immunosuppression. therapeutic decisions in oncology patients with bp are challenging because standard immunosuppressive therapies may carry unacceptable risks in the setting of active malignancy. targeted depletion of b-cells (and auto-antibodies) with rituximab has been reported to be effective in immunotherapy-related bp5 and may offer a more favorable risk profile than traditional immunosuppressive agents, though controlled studies are lacking. a. b. c. skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 82 in sum, the diagnosis of bp should be considered in patients treated with anti-pd-1 or anti-pd-l1 therapy who develop a pruritic rash,1 which should prompt a skin biopsy and evaluation for auto-antibodies. only one case of non-bullous pemphigoid in association with anti-pd-1 therapy has been previously reported.6 our case further supports that immunotherapy-related bp may present with non-bullous skin lesions and additionally emphasizes the need to monitor closely for oral erosions.2 conflict of interest disclosures: none funding: c.l.s. is supported by grant nih k08ar075846 corresponding author: cory l. simpson, m.d., ph.d. department of dermatology hospital of the university of pennsylvania 3600 spruce st., 2 e. gates bldg. #2063 philadelphia, pa 19104 phone: 215-614-1612 fax: 215-615-3140 email: cory.simpson@pennmedicine.upenn.edu references: 1. siegel j, totonchy m, damsky w, et al. bullous disorders associated with anti-pd-1 and anti-pdl1 therapy: a retrospective analysis evaluating the clinical and histopathologic features, frequency, and impact on cancer therapy. j am acad dermatol. 2018;79(6):1081-1088. 2. kridin k, bergman r. assessment of the prevalence of mucosal involvement in bullous pemphigoid. jama dermatol. 2019;155(2):166171. 3. wang ll, moshiri as, novoa r, et al. comparison of c3d immunohistochemical staining to enzyme-linked immunosorbent assay and immunofluorescence for diagnosis of bullous pemphigoid. j am acad dermatol. 2020;83(1):172-178. 4. williams hc, wojnarowska f, kirtschig g, et al. doxycycline versus prednisolone as an initial treatment strategy for bullous pemphigoid: a pragmatic, non-inferiority, randomised controlled trial. the lancet. 2017;389(10079):1630-1638. 5. apalla z, lallas a, delli f, et al. management of immune checkpoint inhibitor-induced bullous pemphigoid. j am acad dermatol. 2020. 6. singer s, nelson ca, lian cg, dewan ak, leboeuf nr. nonbullous pemphigoid secondary to pd-1 inhibition. jaad case reports. 2019;5(10):898-903. mailto:cory.simpson@pennmedicine.upenn.edu skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 293 brief article clinically amyopathic dermatomyositis associated with recurrence of esophageal cancer: a case report anna eversman, bs1, sayeeda ahsanuddin, md2, joel saltzman, md1,3, paula silverman, md1,3, mara g beveridge, md1,2 1case western reserve university school of medicine, cleveland, oh 2university hospitals cleveland medical center, department of dermatology, cleveland, oh 3university hospitals cleveland medical center, department of medical oncology, cleveland, oh dermatomyositis is a rare inflammatory disorder characterized by pathognomonic skin changes and muscle weakness. classic cutaneous findings include: the heliotrope rash, gottron’s papules, and poikilodermatous patches. approximately 20% of patients displaying characteristic skin changes do not develop clinical or enzymatic evidence of muscle inflammation within 6 months of onset, leading to a diagnosis of clinically amyopathic dermatomyositis (cadm).1 muscle weakness rarely occurs after a prolonged delay, suggesting cadm may be a clinical entity distinct from dermatomyositis.2 current literature suggests the incidence of malignancy is lower in cadm patients compared to patients with dermatomyositis.3 it is still necessary for clinicians to screen for malignancy in cadm patients, however, as data on cadm remains limited. we report a case of new-onset cadm associated with recurrent esophageal adenocarcinoma. a 64-year-old female with a history of stage iii esophageal cancer presented in june of 2019 with a one-month history of a pink, pruritic rash involving the face, upper chest, and extremities (figure 1). she denied muscle tenderness or weakness. her esophageal cancer was diagnosed in november of 2018 and was treated with neoadjuvant carboplatin, paclitaxel and concurrent radiation followed by an abstract background: approximately 20% of patients displaying skin changes characteristic of dermatomyositis do not develop clinical or enzymatic evidence of muscle inflammation within 6 months of onset, leading to a diagnosis of clinically amyopathic dermatomyositis (cadm). current literature suggests the incidence of malignancy is lower in cadm patients compared to patients with dermatomyositis. it is still necessary for clinicians to screen for malignancy in cadm patients, however, as data on cadm remains limited. case presentation: we report a case of new-onset cadm associated with recurrent esophageal adenocarcinoma for clinical interest and to add to the limited literature on cadm. conclusion: to date, there is only one report of concurrent cadm and esophageal cancer. we present this case for clinical interest and to add to the limited literature on cadm. introduction case presentation skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 294 figure 1. (a) erythema of the face in a butterfly distribution, (b) poikilodermatous patches on the upper back in a shawl distribution, (c) and pink papules covering the dorsal finger joints. esophagectomy. her past cancer history was also notable for invasive ductal carcinoma of the right breast, diagnosed in january of 2017 and treated with lumpectomy, radiation, anastrozole, and exemestane. she also had multiple colon polyps. of note, the patient had a pet/ct scan four months prior to presentation, which showed no evidence of metastatic disease. physical exam was remarkable for confluent, bright pink patches and plaques on the extensor surface of the upper extremities bilaterally, with perifollicular papules at periphery. a few scattered, pink perifollicular papules were also seen on the thighs. pink, poikilodermatous patches were present in a shawl distribution on the chest and upper back. erythema of the face was present in a butterfly distribution, and pink papules covered the dorsal finger joints. laboratory findings were notable for positive anti-nuclear antibodies (ana) in a homogenous pattern. an ena panel was negative. creatine kinase and aldolase levels were within normal limits. a punch biopsy of the left upper extremity demonstrated basal layer vacuolization with occasional dyskeratosis and a mild superficial lymphocytic infiltrate (figure 2). a sample obtained for direct immunofluorescence was nonreactive. a repeat pet/ct showed hypermetabolic nodular soft tissue thickening at prior surgical sites, as well as two ill-defined hypoechoic lesions with increased fdg uptake in the liver. hypermetabolic mediastinal, celiac, and right internal mammary lymph nodes were also noted, raising concern for residual or recurrent esophageal carcinoma versus breast cancer. expedited oncologic surveillance was discussed with her care team following diagnosis of cadm. biopsies were performed on concerning liver lesions identified by her recent pet scan, and pathology revealed metastatic esophageal adenocarcinoma. the patient’s cutaneous symptoms have improved with an oral a. b. c. skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 295 figure 2: histopathologic examination revealed basal layer vacuolization with occasional dyskeratosis and a mild superficial lymphocytic infiltrate (a, h&e 40x) (b, h&e 20x). prednisone taper, hydroxychloroquine, and topical steroids. treatment of her recurrent esophageal cancer with folfox chemotherapy (folinic acid, 5-fluorouracil, and oxaliplatin) is scheduled to begin this month. to our knowledge, this is the first report of cadm associated with recurrence of esophageal cancer. exacerbations of classic dermatomyositis in the setting of malignancy recurrence are common, however there are few reports of new-onset cadm associated with malignancy recurrence.4 additionally, esophageal cancer is not frequently linked to the inflammatory myopathies.5 to date, there is only one report of concurrent cadm and esophageal cancer.5 we present this case for clinical interest and to add to the limited literature on cadm. dermatomyositis, an inflammatory myopathy, encompasses a spectrum of presentations with variable skin and muscle involvement. as skin changes commonly precede muscle involvement, the diagnosis of cadm is reserved for patients with no clinical or enzymatic evidence of muscle involvement within 6 months of onset.6 cadm refers to both amyopathic disease and cases with subclinical myositis on biopsy, termed hypomyopathic disease.7 the unique clinical presentation of cadm as well as differences in associated antibodies suggest independent analysis of this subset of patients is warranted.2 between 10 and 50% of patients with dermatomyositis have an underlying neoplasm, with cancer of the ovaries, breast, lung, colon, cervix, thyroid, and bladder reported most frequently.6,7 studies on the malignancy risk conferred by cadm have yielded conflicting results. early reports suggested there was no correlation between cadm and malignancy.8 more recent literature, however, revealed cadm and dermatomyositis are associated with an equal age-dependent risk of malignancy.6,7 carcinomas of the nasopharynx, breast, ovary, and lung are commonly reported in patients with cadm.6 patients with autoantibodies in addition to ana are less likely to develop a malignancy, suggesting these antibodies are correlated with true autoimmune etiologies.7 as malignancies may be diagnosed before, during, or after the onset of discussion a. b. skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 296 dermatomyositis, the temporal relationship between these two conditions is unclear. resolution of dermatomyositis has been reported following tumor resection, suggesting the inflammatory myopathy represents an immune response to the cancer.9 it is possible, however, that immunosuppression secondary to dermatomyositis treatment increases the risk of malignancy.10 increased testing and surveillance following the diagnosis of dermatomyositis may also be a contributing factor. independent of the etiology, physicians should be aware of malignancies correlated to inflammatory myopathies to ensure patients undergo appropriate screening. as dermatomyositis and cadm are associated with internal malignancies, additional workup is warranted in both populations. a thorough history, physical examination, and baseline laboratory testing is recommended for all patients with newonset dermatomyositis.11 patients should also be up-to-date on all ageand genderappropriate cancer screening. although further testing may be obtained based on patient history, there are currently no consensus guidelines. imaging is often reserved for patients with additional findings concerning for malignancy.11 as the majority of dermatomyositis patients harboring internal malignancies are otherwise asymptomatic, more liberal use of imaging may be beneficial.10 in a study from leatham et al, malignancies in patients with dermatomyositis were most frequently detected by ct scan. as most malignancies reveal themselves within 5 years of the onset of cutaneous eruption, repeat testing during this interval may also be of utility.7 conflict of interest disclosures: none funding: none corresponding author: mara g beveridge, md 11100 euclid ave lakeside 3500 cleveland, oh 44106 phone: 216-514-8630 email: mara.beveridge@uhhospitals.org references: 1. pinard j, femia an, roman m, et al. systemic treatment for clinically amyopathic dermatomyostitis at 4 tertiary care centers. jama dermatol. 2019;155(4):494-496. 2. sato s, kuwana m. clinically amyopathic dermatomyositis. curr opin rheumatol 2010;22:63943. 3. bowerman k, pearson dr, okawa j, werth vp. malignancy in dermatomyositis: a retrospective study of 201 patients seen at the university of pennsylvania. j am acad dermatol. 2020 jul;83:117-122. 4. goyal s, nousari hc. paraneoplastic amyopathic dermatomyositis associated with breast cancer recurrence. j am acad dermatol.1999;(41):874-875. 5. kikuchi k, seto y, matsubara t, et al. amyopathic dermatomyositis associated with esophageal cancer. int j dermatol. 2008;47:310-311. 6. gerami p, schope jm, mcdonald l, walling hw, sontheimer rd. a systematic review of adult-onset clinically amyopathic dermatomyositis (dermatomyositis siné myositis): a missing link within the spectrum of the idiopathic inflammatory myopathies. j am acad dermatol. 2006;54(4):597613. 7. galimberti f, li y, fernandez ap. clinically amyopathic dermatomyositis: clinical features, response to medications and malignancy-associated risk factors in a specific tertiary-care-centre cohort. br j dermatol. 2016;174(1):158-64. 8. yu, b. a clinical analysis of cutaneous type dermatomyositis. zhongguo yi xue ke xue yuan xue bao. 1994;16:394-396. 9. joseph cg, darrah e, shah aa, et al. association of the autoimmune disease scleroderma with an immunologic response to cancer. science. 2014;343:152-7. 10. leatham h, schadt c, chisolm s, et al. evidence supports blind screening for internal malignancy in dermatomyositis: data from 2 large us dermatology cohorts. medicine (baltimore). 2018;97(2):e9639. 11. sontheimer rd. clinically amyopathic dermatomyositis: what can we now tell our patients? arch dermatol. 2010;146(1):76-80. skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 111 short communications successful treatment of vitiligo with crisaborole 2% ointment william tausend md1, paige hoyer bs1, morgan arnold bs1, keith d. wagner ms1, lindy ross md1, brandon p. goodwin md1, janice wilson md1 1department of dermatology, university of texas medical branch, galveston, tx vitiligo is a common disorder of skin pigmentation resulting from autoimmune destruction of melanocytes. a variety of topical and systemic treatment options have been tried with varying success. here we describe the case of a man with refractory vitiligo successfully treated with topical crisaborole ointment. crisaborole ointment is a topical phosphodiesterase (pde)-4 inhibitor recently fda-approved for the treatment of atopic dermatitis. previous literature has discussed the possible role of systemic pde-4 inhibitors in vitiligo; herein, we discuss the ability of topical crisaborole to accelerate repigmentation in treatment-resistant vitiligo. a hispanic male in his 40s presented to the dermatology clinic with a chief complaint of white spots of the ears and penis. he carried a diagnosis of persistent vitiligo for more than 20 years. the patient had previously attempted therapy with topical steroids for years without any repigmentation. most recently, he used topical calcineurin inhibitors intermittently for years without success. he had no other past medical history, and took no medications. on physical exam, he was noted to have mildly irregular and welldemarcated depigmented macules and patches on the bilateral ears (figure 1) and the glans of the penis. depigmentation was confirmed by examination with wood’s lamp. no epidermal change, scarring, or evidence of an active inflammatory process elsewhere were present on exam. no biopsy was performed. crisaborole 2% ointment was prescribed for application twice daily to the affected areas. the patient chose to only treat his ears and did not treat the lesions on his penis. on follow up one month later, the patient’s ears showed scattered perifollicular repigmentation (figure 2). the penile lesions remained unchanged. the patient declined photographs of his penile lesions, and was subsequently lost to follow up. figure 1: ears prior to treatment with crisaborole. case report introduction skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 112 figure 2: ears after 1 month of therapy with crisaborole 2% ointment. vitiligo is a common cutaneous pigmentary disorder characterized by loss of functional melanocytes in affected skin. though the pathogenesis of vitiligo is unknown, several hypotheses exist, including the autoimmune model, the zinc-a2-glycoprotein model, the viral theory, and the reactive oxidative species theory [1]. first line treatment has traditionally included topical steroids or calcineurin inhibitors in order to diminish cellular immune response. systemic steroids (in high pulsed doses or low daily doses) have also been used to halt the progression of the disease. procedural treatments are also available, such as phototherapy (especially narrow-band uvb), excimer laser, and various surgical autologous grafting techniques. despite an ever growing list of treatments, improvement speed is variable and many patients do not achieve complete re-pigmentation [2]. phosphodiesterase (pde)-4 inhibitors are a class of medications that reduce and prevent inflammation by increasing intracellular levels of cyclic adenosine monophosphate (camp). one member of this class, apremilast, has been previously reported to lead to repigmentation in a case of vitiligo that was resistant to conventional therapies [3]. apremilast is an oral pde-4 inhibitor currently approved for the treatment of moderate to severe plaque psoriasis and psoriatic arthritis in adults. one disadvantage of apremilast, compared to crisaborole, is that it is a systemic medication and thus carries a greater potential risk of side effects, the most commonly reported of which are nausea, diarrhea, headache, and depression, compared to topical therapies [4, 5]. crisaborole ointment is a topical pde-4 inhibitor currently approved the treatment of atopic dermatitis in children and adults [6]. the most common side effect that has been reported with this medication was application site irritation, specifically stinging and burning, which was seen in up to 4% of patients [7]. in this report, it was found that crisaborole ointment applied twice daily led to partial repigmentation in some areas previously resistant to standard topical medications, while areas not treated with crisaborole remained unchanged. crisaborole 2% ointment may be a noninvasive treatment option for vitiligo resistant to standard topical therapy. this is at least the second time that pde-4 inhibitors have been discussed as a potential treatment modality for patients with resistant vitiligo. it is possible that the reported successes of pde-4 inhibitors in vitiligo repigmentation are due to the drug class altering levels of important proand anti-inflammatory cytokines, especially il-17 and il-10. more research is needed to demonstrate the efficacy and safety of topical crisaborole in the treatment of vitiligo and the potential role of pde-4 inhibitors in vitiligo. conflict of interest disclosures: none. funding: none. corresponding author: keith wagner, ms university of texas medical branch galveston, tx kedwagne@utmb.edu discussion mailto:kedwagne@utmb.edu skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 113 references: 1. mohammed g, gomaa a, al-dhubaibi m. highlights in pathogenesis of vitiligo. world j clin cases. 2015;3(3):221-230. 2. dillon a, sideris a, hadi a. advances in vitiligo: an update on medical and surgical treatments. j clin aesthet dermatol. 2017;10(1)15-28. 3. spina d. pde4 inhibitors: current status. br j pharmacol. 2008;155(3):308-315 4. mayo clinc. crisaborole (topical application route). 2019. retrieved from https://www.mayoclinic.org/drugssupplements/crisaborole-topicalapplication-route/side-effects/drg20313098?p=1 accessed 2/7/19 5. huff s, gottwald l. repigmentation of tenacious vitiligo on apremilast. case reports in dermatological medicine. 2017. 6. kailas a. crisaborole: a new and effective nonsteroidal topical drug for atopic dermatitis. dermatologic therapy. 2017;30(5). 7. eichenfield lf, call rs, et al. “long-term safety of crisaborole ointment 2% in children and adults with mild to moderate atopic dermatitis.” j am acad dermatol. 2017;77(4):641-649 presented at fall clinical dermatology | las vegas, nevada | october 18–21, 2018. previously presented at eadv 2018 100 80 60 40 20 0 4440363228242016 48 week r e sp o n d e r ra te ( % ) 86.1% 98.0% durability of response in patients with chronic plaque psoriasis treated with certolizumab pegol over 48 weeks: pooled results from ongoing phase 3, multicenter, randomized, placebo-controlled studies (cimpasi-1, cimpasi-2 and cimpact) m. augustin,1 j. węgłowska,2 m. lebwohl,3 c. paul,4 v. piguet,5,6,7 h. sofen,8 a. blauvelt,9 l. peterson,10 r. rolleri,10 k. reich,11 d. thaçi,12 c. leonardi,13 y. poulin,14 c. arendt,15 a. b. gottlieb16 1institute for health services research in dermatology and nursing (ivdp), university medical center hamburg-eppendorf (uke), hamburg, germany; 2niepubliczny zakład opieki zdrowotnej multimedica, wrocław, poland; 3icahn school of medicine at mount sinai, new york, ny; 4paul sabatier university, toulouse, france; 5cardiff university and university hospital of wales, cardiff, uk; 6division of dermatology, department of medicine, university of toronto, toronto, canada; 7division of dermatology, women’s college hospital, toronto, canada; 8david geffen school of medicine at ucla, los angeles, ca; 9oregon medical research center, portland, or; 10ucb pharma, raleigh, nc; 11sciderm research institute, hamburg, and dermatologikum berlin, germany; 12university hospital of schleswig-holstein campus lübeck, lübeck, germany; 13central dermatology and saint louis university school of medicine, st louis, mo; 14centre de recherche dermatologique du québec métropolitain, québec, canada; 15ucb pharma, brussels, belgium; 16department of dermatology, new york medical college at metropolitan hospital, new york, ny objective • to assess the durability of the initial clinical response to certolizumab pegol in patients with moderate to severe plaque psoriasis over 48 weeks in phase 3 trials. background • plaque psoriasis (pso) is an immune-mediated, inflammatory disease. • treatment options include topicals, phototherapy or systemic medications (including biologics). however, loss of response can occur over time.1 • certolizumab pegol (czp) is a unique fc-free, pegylated, antitumor necrosis factor biologic, approved by both the fda and ema for the treatment of moderate to severe pso.2,3 • in phase 3 trials, czp has demonstrated significant improvements in the signs and symptoms of pso, and a safety profile consistent with the class.4,5 • we assessed durability of the initial week 16 response to czp over a further 32 weeks of treatment. methods study design • data were pooled from three ongoing czp phase 3 trials in adults with pso: cimpasi-1 (nct02326298), cimpasi-2 (nct02326272) and cimpact (nct02346240) (figure 1). • this analysis includes only patients who achieved a ≥75% reduction from baseline in psoriasis area severity index (pasi 75) at week 16, and continued on the same czp dose during the maintenance period. patients • ≥18 years of age with pso for ≥6 months with pasi ≥12, ≥10% body surface area affected and physician’s global assessment ≥3 on a 5-point scale. • candidates for systemic pso therapy, phototherapy and/or photochemotherapy. • exclusion criteria: previous treatment with czp or >2 biologics; history of primary failure to any biologic or secondary failure to >1 biologic; erythrodermic, guttate or generalized pso types; history of current, chronic or recurrent viral, bacterial or fungal infections. study assessments • pasi 75 and pasi 90 (≥90% reduction) responder rates were assessed through weeks 16–48 in patients who achieved pasi 75 at week 16. • pasi 90 responder rates were additionally assessed through weeks 16–48 in patients who achieved pasi 90 at week 16. conclusions • the response to czp was durable, with high response rates maintained through week 48. • czp provides an effective, long-term treatment option for patients with moderate to severe pso. summary after 48 weeks of treatment with certolizumab pegol... czp 200 mgczp 400 mgczp 200 mg czp 400 mg week 16 pasi 75 responders week 16 pasi 90 responders 80% still reported pasi 90 still reported pasi 75 still reported pasi 75 still reported pasi 90 98%86% 89% these data show that czp provides an e�ective, long-term treatment option for patients with moderate to severe psoriasis. 1 fab’ certolizumab pegol figure 1. study design for czp in pso phase 3 trials bw: twice per week; czp: certolizumab pegol; etn: etanercept; ld: czp 400 mg loading dose at weeks 0, 2 and 4 or weeks 16, 18 and 20; pasi: psoriasis area severity index; q2w: every two weeks; q4w: every four weeks. b) cimpact a) cimpasi-1 and cimpasi-2 czp 200 mg q2wa (n=173) czp 400 mg q2w (n=180) age, years, mean (sd) 44.8 (13.0) 44.7 (13.0) male, n (%) 117 (67.6) 114 (63.3) bmi, kg/m2, mean (sd) 30.9 (7.7) 29.6 (6.5) prior biologic use, n (%) 52 (30.1) 55 (30.6) anti-tnf 32 (18.5) 27 (15.0) anti-il-17 17 (9.8) 14 (7.8) anti-il-12/il-23 1 (0.6) 11 (6.1) pso duration, years, mean (sd) 18.1 (12.7) 17.7 (11.9) pasi, mean (sd) 19.9 (7.9) 19.8 (6.8) bsa affected, %, mean (sd) 24.3 (16.0) 24.4 (13.4) pga score, n (%) 3 (moderate) 121 (69.9) 128 (71.1) 4 (severe) 52 (30.1) 52 (28.9) aczp 200 mg q2w patients received czp 400 mg at weeks 0, 2 and 4. bmi: body mass index; bsa: body surface area; czp: certolizumab pegol; il: interleukin; pasi: psoriasis area severity index; pga: physician’s global assessment; sd: standard deviation; tnf: tumor necrosis factor. table 1. demographics and baseline characteristics czp 200 mg q2w (n=173)a czp 400 mg q2w (n=180) figure 2. pasi response through weeks 16–48 in week 16 pasi 75 responders mcmc imputation. aczp 200 mg q2w patients received loading dose of czp 400 mg at weeks 0, 2 and 4. czp: certolizumab pegol; mcmc: markov chain monte carlo; nri: non-responder imputation; pasi: psoriasis area severity index; q2w: every two weeks. a) pasi 75 b) pasi 90 figure 3. pasi 90 response through weeks 16–48 in week 16 pasi 90 responders czp 200 mg q2w czp 400 mg q2w week 48 mcmc, % 80.1 89.0 nri, % 75.0 84.5 100 80 60 40 20 0 4440363228242016 48 week r e sp o n d e r ra te ( % ) 80.1% 89.0%100 80 60 40 20 0 4440363228242016 48 week r e sp o n d e r ra te ( % ) 64.7% 57.8% 77.4% 64.4% 0 initial treatment period (double-blind) maintenance period (double-blind) 48 re-randomization 16 4032week initial treatment period (double-blind) maintenance period (double-blind) <pasi 75 <pasi 50 – open label treatment <pasi 75 <pasi 75 <pasi 75 placebo q2w czp 400 mg q4wetn 50 mg bw washout ld czp 200 mg q2w czp 400 mg q2w czp 400 mg q2w czp 200 mg q2w placebo q2w <pasi 50 entered escape arm (czp 400 mg q2w) 0week 1:2:2 randomization 4832 40 16 czp 200 mg q2wld <pasi 50 withdrawn <pasi 50 withdrawn <pasi 50 withdrawn pasi 50–74 received ld then czp 200 mg q2w placebo q2w <pasi 75 entered escape arm (czp 400 mg q2w) 1:3:3:3 randomization 12 12 ld czp 400 mg q2w statistical analyses • patients who did not achieve pasi 50 (≥50% reduction) at week 32 or later were treated as non-responders at subsequent time points. • missing data and patients withdrawn during weeks 16–48 were imputed using multiple imputation (markov chain monte carlo [mcmc] method). • sensitivity analyses were conducted using non-responder imputation (nri) for all missing data. results • 173 patients receiving czp 200 mg every two weeks (q2w) and 180 patients receiving czp 400 mg q2w achieved a pasi 75 response at week 16 and entered the maintenance period. patient baseline characteristics are shown in table 1. • of patients who achieved a week 16 pasi 75 response: – a high proportion achieved pasi 75 at week 48 (figure 2a) • the proportion of patients who also demonstrated a pasi 90 response was maintained or further increased to week 48 (figure 2b). • pasi 90 responder rates for week 16 pasi 90 responders remained high to week 48 (figure 3). references: 1. piaserico s. et al. j am acad dermatol 2014;70:257—62.e.253; 2. certolizumab pegol prescribing information. available at http://www.accessdata.fda.gov; 3. certolizumab pegol summary of product characteristics. available at http://www.ema.europa.eu/ema; 4. gottlieb ab. et al. j am acad dermatol 2018;79:302—14.e6; 5. lebwohl m. et al. j am acad dermatol 2018;79:266—76.e5. author contributions: substantial contributions to study conception/design, or acquisition/analysis/ interpretation of data: ma, jw, ml, cp, vp, hs, ab, lp, rr, kr, dt, cl, yp, ca, abg; drafting of the publication, or revising it critically for important intellectual content: ma, jw, ml, cp, vp, hs, ab, lp, rr, kr, dt, cl, yp, ca, abg; final approval of the publication: ma, jw, ml, cp, vp, hs, ab, lp, rr, kr, dt, cl, yp, ca, abg. author disclosures: ma: abbvie, almirall, amgen, biogen, boehringer ingelheim, celgene, centocor, eli lilly, glaxosmithkline, hexal, janssen, leo pharma, medac, merck, msd, mundipharma, novartis, pfizer, sandoz, ucb pharma, xenoport; jw: amgen, celgene, coherus, dermira inc., eli lilly, galderma, janssen, leo pharma, merck, pfizer, regeneron, sandoz, ucb pharma; ml: allergan, aqua leo pharma, promius. employee of mount sinai which receives research funds from abbvie, amgen, boehringer ingelheim, celgene, eli lilly, janssen/johnson & johnson, kadmon, medimmune/astra zeneca, novartis, pfizer, valeant, vidac; cp: abbvie, almirall, amgen, boehringer ingelheim, celgene, glaxosmithkline, janssen cilag, leo pharma, eli lilly, novartis, pierre fabre, pfizer, sanofi regeneron, ucb pharma; vp: abbvie, amgen, boehringer ingelheim, celgene, dermira inc., janssen, eli lilly, medimmune, novartis, pfizer, sun pharma, ucb pharma, valeant; hs: abbvie, amgen, boehringer ingelheim, celgene, dermira inc., janssen, eli lilly, medimmune, novartis, pfizer, sun pharma, ucb pharma, valeant; ab: abbvie, aclaris, almirall, amgen, boehringer ingelheim, celgene, dermavant, dermira inc., eli lilly, genentech/roche, glaxosmithkline, janssen, leo pharma, meiji, merck, novartis, pfizer, purdue pharma, regeneron, sandoz, sanofi genzyme, sienna pharmaceuticals, sun pharma, ucb pharma, valeant, vidac. kr: abbvie, affibody, amgen, biogen, boehringer ingelheim, celgene, centocor, covagen, forward pharma, glaxosmithkline, janssen-cilag, kyowa kirin, leo pharma, eli lilly, medac, merck sharp & dohme corp., novartis, ocean pharma, pfizer, regeneron, samsung biopepis, sanofi, takeda, ucb pharma, valeant, xenoport; dt: abbvie, almiral, amgen, boehringer-ingelheim, celgene, dignity, dr. reddy, galapagos, glaxosmithkline, janssen, leo pharma, morphosis, msd, eli lilly, novartis, pfizer, sandoz-hexal, regeneron/ sanofi, ucb pharma; cl: abbvie, actavis, amgen, boehringer ingelheim pharma, celgene, coherus, corrona, dermira inc., eli lilly, galderma, glenmark, janssen, leo pharma, merck, novartis, novella, pfizer, sandoz, stiefel, wyeth, ucb pharma, vitae. treasurer of the international psoriasis council. fellow of the american academy of dermatology. member of the american dermatological association. adjunct professor of dermatology at st. louis university school of medicine. private practice in st. louis, mo; yp: abbvie, baxter, boehringer ingelheim pharma, celgene, centocor/janssen, eli lilly, emd serono, glaxosmithkline, leo pharma, medimmune, merck, novartis, pfizer, regeneron, sanofi genzyme, takeda, ucb pharma; abg: abbvie, allergan, beiersdorf inc., bristol myers squibb, celgene, dermira inc., eli lilly, janssen, incyte, leo pharma, novartis, reddy labs, sun pharmaceutical industries, ucb pharma, valeant; lp, rr, ca: employees of ucb pharma. acknowledgements: the studies were funded by dermira inc. in collaboration with ucb pharma. ucb is the regulatory sponsor of certolizumab pegol in psoriasis. we thank the patients and their caregivers in addition to the investigators and their teams who contributed to this study. the authors acknowledge bartosz łukowski, msc, ucb pharma, brussels, belgium for publication coordination and amelia frizell-armitage, phd, costello medical, cambridge, uk for medical writing and editorial assistance. all costs associated with development of this poster were funded by ucb pharma. czp 200 mg q2w czp 400 mg q2w week 48 mcmc, % 64.7 77.4 nri, % 60.1 73.3 czp 200 mg q2w czp 400 mg q2w week 48 mcmc, % 86.1 98.0 nri, % 79.2 91.7 czp 200 mg q2w (n=173)a czp 400 mg q2w (n=180) czp 200 mg q2w (n=100)a czp 400 mg q2w (n=116) skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 159 rising derm stars® wedding dermatology: a proposed timeline to optimize skin clearance and the avoidance of a true dermatologic emergency winkelmann rr, md1, desai td, md, del rosso jq, do 1unt health sciences, houston, tx over the last five years leading up to 2018, the wedding industry has increased at an annualized rate of 2.6% to a yearly revenue of $78.9 billion.1 women and men are increasingly presenting to dermatology clinics seeking a clear complexion before their own wedding or that of a family member or close friend. a recent pubmed search revealed a complete absence of literature addressing this specific subject. given the lack of resources and guidelines, a knowledge gap may exist among dermatologists with patients presenting for this concern. the issue is confounded by the fact that not all patients present within the same timeline before their wedding. all acne therapies have potential side effects and require variable amounts of treatment duration for the desired response. balancing acne treatment efficacy while mitigating potential side effects with the goal of clear skin on one specific day has never been studied in dermatology. treatment recommendations would be different for patients presenting with 1 year, 6 months, 3 months, 1 month, 1 week, or even 1-2 days before the wedding date. table 1 outlines a proposed timeline of acne treatment options for patients seeking clear skin on one specific day based on the current aad treatment guidelines and expert opinion.2 references: 1. may 2018. ibisworld industry report. tying the knot: rising disposable income will boost industry demand. 2. zaenglein al et al. guidelines of care for the management of acne vulgaris. j am acad dermatol. 2016;75(5):945-73. skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 160 table 1. 2016 aad acne treatment guidelines and proposed timeline for ideal wedding acne treatment. poster presented at the 36th fall clinical dermatology conference | las vegas, nv | october 12-15, 2017 maintenance of response with certolizumab pegol for the treatment of chronic plaque psoriasis: results of a 32-week re-randomized maintenance period from an ongoing phase 3, multicenter, randomized, activeand placebo-controlled study (cimpact) matthias augustin,1 jolanta węgłowska,2 mark lebwohl,3 carle paul,4 vincent piguet,5 howard sofen,6 andrew blauvelt,7 daniel burge,8 luke peterson,9 janice drew,8 robert rolleri9 1institute for health services research in dermatology and nursing, university medical center hamburg-eppendorf, hamburg, germany; 2niepubliczny zakład opieki zdrowotnej multimedica, wrocław, poland; 3icahn school of medicine at mount sinai, new york, ny; 4paul sabatier university, toulouse, france; 5cardiff university and university hospital of wales, cardiff, uk; 6david geffen school of medicine at ucla, los angeles, ca; 7oregon medical research center, portland, or; 8dermira, inc., menlo park, ca; 9ucb biosciences, inc., raleigh, nc introduction • psoriasis affects ~3% of adults in the us1,2 and ~2-6% of adults in europe3; onset can begin at any age, though most patients develop the disease in the third decade of life4 • therapy for patients with plaque psoriasis varies according to the severity of the disease, with limited or mild psoriasis treated with topical therapies and/or phototherapy and more severe disease treated with photochemotherapy, cyclosporine, methotrexate, or biological agents such as tumor necrosis factor (tnf) inhibitors, anti-il17s, and anti-il12/23s • certolizumab pegol (czp) is the only pegylated, fc-free, anti-tnf biologic (figure 1) and is currently under investigation for the treatment of moderate-to-severe chronic plaque psoriasis • previously presented data through week 16 of 3 ongoing, randomized, double-blind, placebo-controlled trials have demonstrated clinically meaningful efficacy and a safety profile consistent with anti-tnf therapy5,6 • cimpact (nct02346240) is designed to assess the efficacy and safety of treatment with czp compared with placebo and etanercept (etn) in adult patients with moderateto-severe chronic plaque psoriasis; results through week 48 for patients initially treated with czp are presented here figure 1. structure of tnf blocking agents certolizumab pegol (cimzia ® ) fab’ fragment pegylated fab peg etanercept (enbrel ® ) infliximab (remicade ® ) receptor/fc fusion protein monoclonal antibody adalimumab (humira ® ) golimumab (simponi™) receptor fab igg1 fc igg1 fc = murine = humanized fab: fragment antigen-binding; fc: fragment crystallizable; igg: immunoglobulin g; peg: polyethylene glycol methods study design • cimpact is an ongoing phase 3, randomized, multinational, parallel-group, placeboand active-controlled trial • patients were randomized 3:3:1:3 to czp 400 mg every 2 weeks (q2w), czp 200 mg q2w (after an initial loading dose of 400 mg at weeks 0, 2, and 4), or placebo q2w for 16 weeks or etn twice weekly for 12 weeks (figure 2) • at week 16, czpand etn-treated pasi 75 responders were re-randomized and continued for 32 weeks of maintenance treatment: – from czp 400 mg q2w to 400 mg q2w, 200 mg q2w, or placebo q2w – from czp 200 mg q2w to 400 mg every 4 weeks (q4w), 200 mg q2w, or placebo q2w – from etn to czp 200 mg q2w (after loading dose) or placebo q2w • at week 16, placebo-treated pasi 75 responders continued placebo q2w for 32 weeks of maintenance treatment • at week 16, pasi 75 nonresponders entered an escape arm for treatment with czp 400 mg q2w figure 2. study design 0 randomization re-randomization 16 4840 443212 36week initial treatment period (double-blind) maintenance period (double-blind) 1:3:3:3 < pasi 50 – withdrawn < pasi 75 < pasi 50 – open label treatment < pasi 75 < pasi 75 < pasi 75 placebo q2w placebo q2w czp 400 mg q4w czp 200 mg q2w czp 400 mg q2w escape czp 400 mg q2w ld etn 50 mg bw washout ld czp 200 mg q2w czp 400 mg q2w bw, twice weekly; czp, certolizumab pegol; etn, etanercept; ld, loading dose of czp 400 mg at weeks 0, 2, and 4 or weeks 16, 18, and 20; pasi 50, ≥50% reduction in psoriasis area and severity index (pasi); pasi 75, ≥75% reduction in pasi; q2w, every 2 weeks; q4w, every 4 weeks patients • eligible patients were ≥18 years of age, had moderate-to-severe chronic plaque psoriasis for ≥6 months with a baseline psoriasis area and severity index (pasi) ≥12, affected body surface area (bsa) ≥10%, and physician’s global assessment (pga; 5-point scale) ≥3 • patients had to be candidates for systemic psoriasis therapy, phototherapy, and/or photochemotherapy • patients were excluded if they had erythrodermic, guttate, or generalized pustular forms of psoriasis; previous treatment with czp, etn, or >2 biologics (including anti-tnf); or history of primary failure to any biologic or secondary failure to >1 biologic study assessments • the primary endpoint was pasi 75 (≥75% reduction in pasi; czp vs placebo) responder rate at week 12 • secondary endpoints included: – pga 0/1 (‘clear’ or ‘almost clear’ with ≥2-category improvement; czp vs placebo), pasi 90 (≥90% reduction in pasi; czp vs placebo), and pasi 75 (czp vs etn) responder rates at week 12; pasi 75, pga 0/1, and pasi 90 responder rates (czp vs placebo) at week 16 – pasi 75 responder rate at week 48 for week 16 pasi 75 responders • other efficacy variables included: – pga 0/1 and pasi 90 responder rates at week 48 for week 16 pasi 75 responders • safety evaluation included treatment-emergent adverse events (teaes), physical examinations, clinical laboratory parameters, and blood pressure monitoring statistical analysis • week 12 and week 16 pasi 75, pga 0/1, and pasi 90 responder rates were analyzed via a logistic regression model with factors for treatment, region, and prior biologic exposure (yes/no); the markov chain monte carlo (mcmc) method7 for multiple imputation was used to account for missing data • multiplicity was controlled for the primary and secondary endpoints via a fixed-sequence testing procedure • week 48 pasi 75, pga 0/1, and pasi 90 responder rates were based on nonresponse imputation and are summarized using descriptive statistics results patient disposition, demographics, and baseline characteristics • of 559 patients randomized, 535 (95.7%) completed week 16 (figure 3) • of 234 czp-treated pasi 75 responders who were re-randomized into the maintenance period of the trial, 222 (94.9%) completed week 48 (figure 3) • patient demographics and baseline characteristics were similar between groups (table 1) figure 3. patient disposition completed week 16 placebo n=57 n=55a (96.5%) discontinued 11 adverse event 4 lack of efficacy 1 protocol violation 1 lost to follow-up 2 consent w/d 2 other 1 discontinued 6 adverse event 1 lost to follow-up 1 consent w/d 3 other 1 discontinued 5 adverse event 1 lost to follow-up 2 consent w/d 1 other 1 discontinued 1 other 1 discontinued 2 adverse event 1 consent w/d 1 discontinued 2 lost to follow-up 1 consent w/d 1 discontinued 4 adverse event 2 consent w/d 1 other 1 discontinued 2 consent w/d 1 other 1 discontinued 3 consent w/d 2 other 1 etn n=170 pasi 75 responder and entered maintenance completed week 48 n=44n=22 n=44 czp 200 mg q2w n=165 czp 400 mg q2w n=167 n=159b (93.5%) n=159 (96.4%) n=159 (96.4%) escapec n=53 escapec n=53 escapec n=85 escapec n=85 escapec n=49 escapec n=49 n=43 (97.7%) n=43 (97.7%) n=20 (90.9%) n=20 (90.9%) n=40 (90.9%) n=40 (90.9%) n=23 (92.0%) n=23 (92.0%) n=49 (100%) n=49 (100%) n=50 n=49dn=25 n=162 (97.0%) n=162 (97.0%) escapec n=36 escapec n=36 n=47 (94.0%) n=47 (94.0%) screened n=733 randomized n=559 aplacebo-treated pasi 75 responders at week 16 (n=2) continued placebo betn-treated pasi 75 responders at week 16 (n=74) were re-randomized to placebo (n=24) or czp 200 mg q2w (n=50) cpasi 75 nonresponders at week 16 entered the escape arm for treatment with czp 400 mg q2w dtwo patients completed week 16 but did not enter maintenance period (1 loss to follow-up; 1 consent withdrawn) ■, czp 400 mg q4w; bw, twice per week; czp, certolizumab pegol; etn, etanercept; pasi 75, ≥75% reduction in psoriasis area and severity index; q2w, every 2 weeks; q4w, every 4 weeks; w/d, withdrawn table 1. patient demographics and baseline disease characteristics placebo (n=57) etn (n=170) czp 200 mg q2w (n=165) czp 400 mg q2w (n=167) demographics age (years), mean ± sd 46.5 ± 12.5 44.6 ± 14.1 46.7 ± 13.5 45.4 ± 12.4 male, n (%) 34 (59.6) 127 (74.7) 113 (68.5) 107 (64.1) white, n (%) 57 (100) 163 (95.9) 158 (95.8) 162 (97.0) geographic region, n (%) north america central/eastern europe western europe 10 (17.5) 36 (63.2) 11 (19.3) 29 (17.1) 111 (65.3) 30 (17.6) 26 (15.8) 107 (64.8) 32 (19.4) 27 (16.2) 109 (65.3) 31 (18.6) weight (kg), mean ± sd 93.7 ± 29.7 88.6 ± 20.7 89.7 ± 20.6 86.3 ± 20.0 bmi (kg/m2), mean ± sd 31.2 ± 8.5 29.5 ± 6.3 29.8 ± 6.1 28.9 ± 5.9 baseline disease characteristics duration of psoriasis at screening (years), mean ± sd 18.9 ± 12.9 17.4 ± 12.0 19.5 ± 13.2 17.8 ± 11.5 concurrent psoriatic arthritis, n (%) 12 (21.1) 27 (15.9) 27 (16.4) 24 (14.4) pasi, mean ± sd 19.1 ± 7.1 21.0 ± 8.2 21.4 ± 8.8 20.8 ± 7.7 bsa (%), mean ± sd 24.3 ± 13.8 27.5 ± 15.5 28.1 ± 16.7 27.6 ± 15.3 pga, n (%) 3: moderate 4: severe 40 (70.2) 17 (29.8) 115 (67.6) 55 (32.4) 114 (69.1) 51 (30.9) 113 (67.7) 54 (32.3) dlqi, mean ± sd 13.2 ± 7.6 14.1 ± 7.4 12.8 ± 7.0 15.3 ± 7.3 prior biologic use,a n (%) anti-tnf anti-il17 11 (19.3) 5 ( 8.8) 8 (14.0) 51 (30.0) 8 ( 4.7) 39 (22.9) 44 (26.7) 4 ( 2.4) 38 (23.0) 48 (28.7) 4 ( 2.4) 35 (21.0) apatients may have had exposure to >1 prior biologic but ≤2 per exclusion criteria bmi, body mass index; bsa, body surface area; czp, certolizumab pegol; dlqi, dermatology life quality index; etn, etanercept; il, interleukin; pasi, psoriasis area and severity index; pga, physician’s global assessment; q2w, every 2 weeks; sd, standard deviation; tnf, tumor necrosis factor efficacy baseline to week 16 • at week 12, pasi 75 responder rates were higher for czp 400 mg q2w and czp 200 mg q2w versus placebo (66.7% and 61.3% vs 5.0%; p<0.0001 for both) • also at week 12, responder rates were greater for czp 400 mg q2w and czp 200 mg q2w versus placebo for pga 0/1 (50.3% and 39.8% vs 1.9%; p<0.0001 and p=0.0004, respectively) and pasi 90 (34.0% and 31.2% vs 0.2%, p<0.0001 for both) • at week 16, responder rates were greater for czp 400 mg q2w and czp 200 mg q2w versus placebo for pasi 75 (74.7% and 68.2% vs 3.8%), pga 0/1 (58.4% and 48.3% vs 3.4%), and pasi 90 (49.1% and 39.8% vs 0.3%) (p<0.0001 for all) • czp 400 mg q2w achieved superiority to etn at week 12 (p=0.0152); czp 200 mg q2w achieved noninferiority to etn at week 12 (95% confidence interval: -2.9–18.9, within the prespecified noninferiority margin of 10%) week 16 to week 48 • among week 16 pasi 75 responders, week 48 pasi 75 (figure 4a), pga 0/1 (figure 4b), and pasi 90 (figure 4c) responder rates were greater in the patients re-randomized to czp compared with placebo, with the highest rates seen among patients receiving czp 400 mg q2w in both the initial and maintenance periods figure 4. pasi 75, pga 0/1, and pasi 90 responder rates from week 16 to week 48 in week 16 pasi 75 responders 100 80 60 40 20 0 r es po nd er r at e (% ) week 16 20 24 28 32 36 40 44 48 88.6% 79.5% 45.5% 100 80 60 40 20 0 week 16 20 24 28 32 36 40 44 48 98.0% 80.0% 36.0% 100 80 60 40 20 0 r es po nd er r at e (% ) week 16 20 24 28 32 36 40 44 48 70.5% 61.4% 72.7% 81.8% 68.2% 13.6% 100 80 60 40 20 0 week 16 20 24 28 32 36 40 44 48 87.8% 64.0% 81.6% 84.0% 72.0% 12.0% 100 80 60 40 20 0 r es po nd er r at e (% ) week 16 20 24 28 32 36 40 44 48 68.2% 61.4% 59.1% 72.7% 50.0% 18.2% 100 80 60 40 20 0 week 16 20 24 28 32 36 40 44 48 87.8% 60.0% 62.0% 75.5% 52.0% 12.0% czp 200 mg q2w czp 400 mg q4w (n=44) czp 200 mg q2w (n=44) placebo q2w (n=22) czp 400 mg q2w czp 200 mg q2w (n=50) czp 400 mg q2w (n=49) placebo q2w (n=25) a. pasi 75 b. pga 0/1 c. pasi 90 missing data were imputed using nonresponse imputation czp, certolizumab pegol; pasi 75, ≥75% reduction in psoriasis area and severity index (pasi); pasi 90, ≥90% reduction in pasi; pga 0/1, ‘clear’ or ‘almost clear’ with ≥2-category improvement in physician’s global assessment (5-point scale); q2w, every 2 weeks; q4w, every 4 weeks safety • from baseline to week 12, teae/serious teae incidence rates per 100 patient-years were 309.2/10.6 for czp 400 mg q2w, 299.5/2.7 for czp 200 mg q2w, 393.3/41.0 for placebo, and 295.6/2.7 for etn • from baseline to week 48 – percentage of patients experiencing any teae was similar between czp 400 mg q2w and czp 200 mg q2w groups and few patients discontinued due to teaes (table 2) – serious teaes were infrequent in the czp groups (table 2) • from baseline to week 48, incidence rates of serious infections and infestations per 100 patient-years were 2.9 for czp 400 mg q2w and 1.9 for czp 200 mg q2w • 1 patient in the escape arm, after 22 weeks of czp 400 mg q2w (combined initial and maintenance periods), was diagnosed with primary progressive multiple sclerosis during evaluation for low back pain. the subject reported a 2-year history of recurrent falls (none during study), and an mri revealed lesions consistent with ms; this event was unrelated to treatment according to the investigator table 2. adverse events from baseline to week 48 by czp dose taken at time of teae czp 200 mg q2wa,b (n=265) czp 400 mg q2wa (n=354) teaes, n (%) [incidence ratec] any drug-relatedd serious 175 (66.0) [214.0] 40 (15.1) 12 ( 4.5) [ 7.7] 230 (65.0) [201.3] 58 (16.4) 23 ( 6.5) [ 11.3] discontinuations due to teae, n (%) 4 ( 1.5) 11 ( 3.1) deaths, n (%) 0 0 most frequently reported teaes (≥5% in any group), n (%) [incidence ratec] nasopharyngitis upper respiratory tract infection hypertension viral upper respiratory tract infection 35 (13.2) [23.6] 16 ( 6.0) [10.5] 10 ( 3.8) [ 6.5] 14 ( 5.3) [ 9.1] 44 (12.4) [22.6] 29 ( 8.2) [14.4] 17 ( 4.8) [ 8.3] 8 ( 2.3) [ 3.8] teaes of interest, n (%) [incidence ratec] infections and infestations serious infections and infestations multiple sclerosis microscopic colitis depression malignancy 108 (40.8) [93.8] 3 ( 1.1) [ 1.9]e 0 0 4 ( 1.5) [ 2.5] 0 132 (37.3) [79.7] 6 ( 1.7) [ 2.9]f 1 ( 0.3) [ 0.5]g 1 ( 0.3) [ 0.5] 1 ( 0.3) [ 0.5] 2 ( 0.6) [ 1.0]h apatients who switched doses could have been counted in both czp doses bpatients receiving czp 400 mg q4w were included in the czp 200 mg q2w group (same cumulative monthly dose) cincidence of new cases per 100 patient-years dincidence rate not calculated egastroenteritis, pancreas infection, and pneumonia fescherichia coli sepsis and pyelonephritis in the same subject, endophthalmitis, pneumonia, sepsis, erysipelas, and tuberculosis gprimary progressive multiple sclerosis; incidental finding during evaluation for low back pain and considered unrelated to treatment according to the investigator hanaplastic oligodendroglioma, keratoacanthoma czp, certolizumab pegol; teae, treatment-emergent adverse event; q2w, every 2 weeks conclusions • czp 400 mg q2w and czp 200 mg q2w demonstrated statistically significant and clinically meaningful improvements in signs and symptoms of moderate-to-severe chronic plaque psoriasis versus placebo at weeks 12 and 16 • czp 400 mg q2w was superior and czp 200 mg q2w was noninferior to etn for pasi 75 responder rate at week 12 • among czp-treated week 16 pasi 75 responders, those who were re-randomized to czp continued to have clinically meaningful responses in pasi 75, pga 0/1, and pasi 90 through week 48 that were well above the responses observed for those re-randomized to placebo – across efficacy endpoints, treatment with czp 400 mg q2w in both the initial and maintenance periods provided greater efficacy than either reducing the dose to czp 200 mg q2w after pasi 75 was achieved or treatment with czp 200 mg q2w in both the initial and maintenance periods – the maintenance dosing regimens of czp 200 mg q2w and czp 400 mg q4w (same cumulative monthly dose) provided similar efficacy – patients initially treated with czp and re-randomized to placebo had a considerable loss of efficacy over time; no episodes of rebound were reported • the safety profile of czp appears to be consistent with the known safety profile of anti-tnf therapy in patients with moderate-to-severe chronic plaque psoriasis; no new safety signals were identified with either dose through 48 weeks of treatment references 1. rachakonda et al. j am acad dermatol. 2014;70(3):512-6. 2. kurd et al. j am acad dermatol. 2009;60(2):218-24. 3. danielsen et al. br j dermatol. 2013;168(6):1303-10. 4. farber et al. dermatologica. 1974;148(1):1-18. 5. gottlieb et al. oral presentation at: 75th annual meeting of the american academy of dermatology; march 3-7, 2017; orlando, fl. abstract 5077. 6. lebwohl et al. poster presentation at: 13th annual maui derm for dermatologists; march 20-24, 2017; maui, hi. abstract 3120. 7. sun. application of markov chain monte-carlo multiple imputation method to deal with missing data from the mechanism of mnar in sensitivity analysis for a longitudinal clinical trial. in: chen et al. monte-carlo simulation-based statistical modeling. singapore, springer; 2017:233-52. acknowledgements this study and all costs associated with the development of this poster were funded by dermira, inc. dermira and ucb are in a strategic collaboration to evalutate the efficacy and safety of certolizumab pegol in the treatment of moderate-tosevere plaque psoriasis. medical writing support was provided by prescott medical communications group (chicago, il). author disclosures ma: consulting honoraria and/or speaker fees for clinical trials sponsored by companies that manufacture drugs used for the treatment of psoriasis including: abbvie, almirall, amgen, biogen, boehringer ingelheim, celgene, centocor, eli lilly and company, gsk, hexal, janssen-cilag, leo pharma, medac, merck, msd, mundipharma, novartis, pfizer, sandoz, ucb and xenoport. jw: investigator and/or speaker: amgen, celgene, coherus, dermira, inc., eli lilly, galderma, janssen, leo pharma, merck, pfizer, regeneron, sandoz, ucb pharma. ml: research/grant support: abbvie, amgen, boehringer ingelheim, celgene, eli lilly and company, janssen/johnson & johnson, leo pharma, medimmune/astrazeneca, novartis, pfizer, sun pharma, ucb pharma, valeant, and vidac. consulting fees: allergan. cp: investigator and consultant: abbvie, almirall, amgen, boehringer ingelheim, celgene, eli lilly, janssen-cilag, leo pharma, novartis, pfizer, pierre fabre, sanofi, ucb. vp: consulting honoraria and/or speaker fees: abbvie, almirall, celgene, janssen, novartis, and pfizer. support to vp department: abbvie, almirall, alliance, beiersdorf uk ltd, biotest, celgene, dermal, eli lilly, galderma, genus pharma, globemicro, janssen-cilag, laroche-posay, l’oreal, leo pharma, meda, msd, novartis, pfizer, samumed, sinclair pharma, spirit, stiefel, thornton ross, typham, ucb. hs: consulting honoraria, clinical investigator and/or speaker fees: abbvie, amgen, boehringer ingelheim, celgene, dermira inc., janssen, eli lilly, medimmune/astrazeneca, novartis, pfizer, sun pharma, ucb pharma, valeant. ab: consulting and/or honoraria: abbvie, amgen, boehringer ingelheim, celgene, dermira, inc., genentech, janssen, eli lilly, merck, novartis, pfizer, regeneron, sandoz. db, jd: employees of dermira, inc. lp, rr: employees of ucb biosciences, inc. fc17posterdermiraaugustinmaintenanceofresponse32wks.pdf skin july 2021 1295 proof returned skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 434 brief article retiform purpura in the setting of covid-19: a harbinger of underlying coagulopathy and severe disease course gabrielle brody, bs1, michael o. nguyen, md, phd2, delila pouldar foulad, md2, nathan w. rojek, md 2 1 university of california, irvine, school of medicine, irvine, ca 2 university of california, irvine, department of dermatology, irvine, ca while covid-19 is most known for its respiratory presentation, other organ systems are by no means unscathed. here, we report a case of retiform purpura associated with covid-19 pneumonia and highlight how retiform purpura may be a useful indicator for future clinical course. a 58-year-old otherwise healthy woman presented to the emergency department in acute hypoxic respiratory distress secondary to covid-19 pneumonia diagnosed ten days prior at an outside care facility. one day prior to admission, she developed significant shortness of breath and required home oxygen. as her pulmonary status further declined, she presented to the emergency department with an oxygen saturation of 79%. nasopharyngeal swab for pcr testing of covid-19 confirmed active infection. the patient had not received any covid-19 vaccines. labs were notable for elevations in d-dimer (3,160 ng/ml), c-reactive protein (10mg/dl), lactate dehydrogenase (569 u/l), and troponin (26 ng/l), correlating with severe covid-19 infection.1 chest x-ray revealed diffuse opacities consistent with covid-19 pneumonia and initial cta was negative for pulmonary embolism. physical exam was significant for an exquisitely tender, violaceous, stellate plaque with central necrosis on the right hip (fig. 1), which was first noticed six days prior to presentation. notably, she had no medication exposures except for longstanding vitamin c and vitamin d supplementation, no recent travel, and no signs concerning for either abstract while the majority of covid-19 cases are mild and can be managed in the outpatient setting, more severe cases have proven to be a clinical challenge. while some cases demonstrate a more slow and indolent decline, others seem to deteriorate rapidly with little forewarning. the current literature has connected retiform purpura as a cutaneous manifestation associated with severe covid-19 infections, however timing of cutaneous presentation and severe clinical covid-19 symptoms has not been well described. here we report a case of a 58-year-old female who developed retiform purpura nearly a week prior to the development of any significant covid-19 symptoms. this case demonstrates that retiform purpura is not only associated with severe covid-19 disease, but can present prior to symptom onset and should be seen as a harbinger for impending clinical deterioration. introduction case report skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 435 malignancy or connective tissue disease. her findings were determined to be clinically consistent with retiform purpura secondary to covid-19 infection. prophylactic anticoagulation with enoxaparin 40mg was initiated. figure 1. violaceous stellate plaque with central necrosis on the right lateral hip, consistent with retiform purpura on day of admission. on the fifth day of admission, the patient developed worsening pleuritic chest pain, hypoxia and cough. additional labs revealed an increased d-dimer from 3,160 to >20,000 ng/ml, repeat cta demonstrated new multiple segmental and subsegmental pulmonary emboli, and lower extremity ultrasound with doppler showed a nonocclusive right popliteal vein thrombus. the patient was discharged on hospital day eight on six liters of oxygen, a ten-day course of dexamethasone, and an extended course of therapeutic anticoagulation with apixaban. two weeks after discharge, the patient was reassessed and the retiform purpuric plaque had progressed with expected central necrotic ulceration (fig. 2). during this time course, she did not develop any other new cutaneous lesions. figure 2. progression of retiform purpura with central necrotic ulceration on right lateral hip two weeks after discharge. there is a vast array of dermatologic manifestations reported in association with covid-19, which are grouped into seven morphologic categories: morbilliform, perniolike, urticarial, macular erythema, vesicular, papulosquamous, and retiform purpura.2 retiform purpura is one of the least represented dermatologic manifestations, accounting for just 6.4% of cases, and corresponds with severe covid-19 infection.2 a recent study by conforti et al reported that of 11 patients with covid-19 and retiform purpura, 100% were hospitalized, 82% developed acute respiratory distress and 91% required ecmo discussion skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 436 and/or ventilation.2 the reason for its association with high disease burden is still being elucidated. magro et al. noted that patients with pernio-like lesions secondary to covid-19 who have mild respiratory symptoms and good outcomes have a strong inflammatory response with low viral loads, while patients with retiform purpura with severe covid-19 disease have minimal interferon response, high viral loads and profound vasculopathy. it is hypothesized that this difference in microenvironment possibly allows for unchecked viral replication and rampant inflammatory activation.3 this case highlights the seriousness of retiform purpura in covid-19 patients as a cutaneous finding concerning for an underlying vasculopathy that may precede further acute thromboembolic events and a worsening course of disease. the presence of retiform purpura in patients with covid-19 therefore merits close clinical monitoring for the risk of acute decompensation and discussion of the benefits and risks of anticoagulant therapy for optimizing outcomes. conflict of interest disclosures: none funding: none corresponding author: gabrielle brody, bs 843 health sciences road hewitt hall 1001 irvine, ca 92697 email: gabbynbrody@gmail.com references: 1. velavan tp, meyer cg. mild versus severe covid-19: laboratory markers. int j infect dis. 2020;95:304-307. doi:10.1016/j.ijid.2020.04.061 2. freeman ee, mcmahon de, lipoff jb, et al. the spectrum of covid-19–associated dermatologic manifestations: an international registry of 716 patients from 31 countries. j am acad dermatol. 2020;83(4):1118-1129. doi:10.1016/j.jaad.2020.06.1016 3. magro c, mulvey j, laurence j, et al. the differing pathophysiologies that underlie covid-19associated perniosis and thrombotic retiform purpura: a case series conflicts of interest. br j dermatol. 2020. doi:10.1111/bjd.19415 conclusion skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 144 rising derm stars® cell cycle activators and tumor suppressors that correlate with melanoma progression michelle min, md1, byungwoo ryu, phd, rhoda alani, md 1department of dermatology, icahn school of medicine at mount sinai, new york, ny background/objectives: melanoma accounts for the highest numbers of skincancer related deaths, and incidence of cutaneous melanoma continues to rise.1 good prognosis is highly dependent on early detection and appropriate staging.2 in addition to our current clinical and histological prognostic indicators, there may be a role for gene expression biomarkers in complementing our current melanoma staging and tumor burden assessment.3 in this study, we sought to evaluate the potential utility of melanoma progressionassociated genes as biomarkers for disease burden in human skin tissue samples. based on previous microarray studies, primary genes of interest were hells, ncaph, and spint2.4 hells and ncaph have been shown to be cell cycle activators upregulated in aggressive metastatic tumor cell lines in comparison to less-aggressive primary tumor cell lines. spint2 has been implicated as a tumor suppressor gene in multiple cancers; its expression induces cell apoptosis and tumor suppression in vivo. methods: after defining the panel of melanoma biomarkers to evaluate, we optimized a multiplex reaction to efficiently quantify rna for our genes of interest from small quantities of tissue. quantitative realtime polymerase chain reaction (qrt-pcr) was performed to quantify and compare rna levels in human skin tissue samples of nevi (n=12), primary melanoma (n=12), and metastatic melanoma (n=12). while ncaph expression levels were difficult to measure due to minimal expression in human tissue, we were able to successfully quantify hells and spint2. results: hells expression levels were remarkably higher in metastatic melanoma compared to benign nevi (p=0.02) and primary melanoma (p=0.05) (figure 1a). meanwhile, spint2 expression levels were almost nonexistent in metastatic skin samples; this was evident when comparing metastatic melanoma to nevi (p=0.03) and primary melanoma (p=0.03) (figure 1b). there was no statistical difference between nevi and primary melanoma (p=0.11 for hells, p=0.31 for spint2). conclusion: our assay system proved sensitive in detecting differences in expression levels of hells and spint2 in metastatic melanoma compared to benign nevi and primary melanoma. such novel biomarkers help us further understand the biology of melanoma, with potential clinical implications in prognosis, therapy, and detection of treatment response and tumor recurrence. skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 145 figure 1. statistical analysis shows hells is upregulated (a) while spint2 is downregulated (b) in metastastatic melanoma (mm) compared to benign nevi and primary melanoma (pm). references: 1. guy gp jr, thomas cc, thompson t, watson m, massetti gm, richardson lc; centers for disease control and prevention (cdc). vital signs: melanoma incidence and mortality trends and projections united states, 1982-2030. mmwr morb mortal wkly rep. 2015 jun 5;64(21):591-6. 2. schramm, s.j., campain, a.e., scolyer, r.a., yang, y.h., and mann, g.j. review and cross-validation of gene expression signatures and melanoma prognosis. j invest dermatol. 2012; 132: 274–283. 3. gershenwald je, et al. melanoma staging: evidence-based changes in the american joint committee on cancer eighth edition cancer staging manual. ca cancer j clin. 2017 nov;67(6):472492. 4. ryu b, kim ds, deluca am, alani rm. comprehensive expression profiling of tumor cell lines identifies molecular signatures of melanoma progression. plos one. 2007 jul 4;2(7):e594. introduction • acne vulgaris is a prevalent chronic, inflammatory skin disorder that affects most of the population at some point in their life1 • oral minocycline and doxycycline are considered first-line therapy for the treatment of moderate-to-severe acne but are associated with potentially serious systemic side effects2 • fmx101 4% is the first stable topical foam formulation of minocycline that has been shown to be an effective and well-tolerated treatment for acne – phase 2 clinical trial – 2 double-blind phase 3 pivotal studies, study fx2014-04 and study fx2014-053,4 • a third phase 3 study (fx2017-22) was conducted to further evaluate the efficacy and safety of daily topical administration of fmx101 4% vs vehicle foam for a period of 12 weeks in the treatment of moderate-to-severe acne vulgaris – multicenter, randomized, double-blind, vehicle-controlled, 2-arm study methods • fx2017-22, a phase 3 multicenter (89 sites), randomized, double-blind, vehicle-controlled, 2-arm study, further evaluated the efficacy and safety of topical fmx101 4% in the treatment of moderate-to-severe acne vulgaris (figure 1) – subjects were randomized 1:1 to receive either fmx101 4% or vehicle foam – foam was self-applied once-daily for 12 weeks figure 1. study design methods 3 ➢ fx2017-22, a phase 3 multicenter (89 sites), randomized, double-blind, vehicle-controlled, 2-arm study, further evaluated the efficacy and safety of topical fmx101 4% in the treatment of moderate-to-severe acne vulgaris (figure 1) o subjects were randomized 1:1 to receive either fmx101 4% or vehicle foam o foam was self-applied daily for 12 weeks • • ae=adverse event; iga=investigator’s global assessment. *due to quality issues identified at one center, 19 subjects were prospectively removed from the intent-to-treat (itt) population. figure 1. study design. • • ‒ ‒ • • • • ae=adverse event; iga=investigator’s global assessment. adue to quality issues identified at one center, 19 subjects were prospectively removed from the intent-to-treat (itt) population. results • 1507 subjects were enrolled in the study • baseline demographics and disease characteristics are shown in table 1 table 1. baseline demographics and disease characteristics fmx101 4% (n=738) vehicle foam (n=750) mean age, years 20.2 20.6 age distribution, n (%) 9-12 yr 13-17 yr >18 yr 42 (5.7) 321 (43.5) 375 (50.8) 41 (5.5) 309 (41.2) 400 (53.3) male, n (%) female, n (%) 278 (37.7) 460 (62.3) 281 (37.5) 469 (62.5) ethnicity, n (%) white black other 571 (77.4) 125 (16.9) 42 (5.7) 560 (74.7) 144 (19.2) 46 (6.1) inflammatory lesion count, mean (sd) 30.7 (8.89) 30.8 (8.27) noninflammatory lesion count, mean (sd) 49.7 (19.70) 49.6 (19.47) total lesion count, mean (sd) 80.4 (22.7) 80.3 (22.4) iga score, n (%) 3 – moderate 4 – severe 620 (84.0) 118 (16.0) 626 (83.5) 124 (16.5) figure 2. absolute change in inflammatory lesion count from baseline at week 12 • at week 12, subjects treated with fmx101 4% had a statistically significantly greater reduction in the number of inflammatory lesions from baseline as compared with the vehicle treatment group, p<0.0001 (figure 2) ancova, itt population, mi. ancova=analysis of covariance. figure 3. iga treatment success at week 12 • at week 12, the proportion of subjects achieving iga treatment success in the fmx101 4% treatment group was statistically significantly higher than in the vehicle treatment group, p<0.0001 (figure 3) cochrane mantel-haenszel test, stratified by analysis center, itt population, mi. figure 4: absolute change of noninflammatory lesion count at week 12 • at week 12, the absolute change in noninflammatory lesion count in the fmx101 4% treatment group was statistically significantly greater than in the vehicle treatment group, p<0.01 (figure 4) ancova, itt population, mi. figure 5. percentage change from baseline to week 12 in inflammatory lesions by visit • the percentage reduction in inflammatory lesions was statistically significantly greater for fmx101 4% vs vehicle at all visits – week 3, 6, 9, and 12 (figure 5) ancova, itt population, observed cases. *p≤.0001. table 2. summary of treatment-emergent adverse events (teaes) in safety populationa fmx101 4% (n=737) vehicle (n=747) subjects with any teae, n (%) 193 (26.2) 183 (24.5) number of teaes 255 235 subjects with any serious teae, n (%) 1 (0.1) 4 (0.5) number of serious teaes 1b 5c asafety population includes all randomized subjects who used at least 1 dose of study drug. bspontaneous abortion. cgastrointestinal disorders, spontaneous abortion, cholecystitis. table 3. summary of subject discontinuation fmx101 4% vehicle subjects discontinued, n (%) 89 (12.1) 106 (14.1) reason for discontinuation adverse event abnormal laboratory result lost to follow-up subject request protocol deviation other 3 (0.4) 1 (0.1) 34 (4.6) 36 (4.9) 6 (0.8) 9 (1.2) 2 (0.3) 0 (0.0) 39 (5.2) 53 (7.1) 4 (0.5) 8 (1.1) table 4. nondermal and dermal aes fmx 101 4% vehicle one or more, n (%) 193 (26.2) 183 (24.5) nondermal aes in ≥1% of subjects, n (%) urti viral urti headache ck increased influenza 31 (4.2) 16 (2.2) 14 (1.9) 14 (1.9) 11 (1.5) 26 (3.5) 22 (2.9) 11 (1.5) 6 (0.8) 4 (0.5) dermal aes in ≥1% of subjects, n (%) acne 22 (3.0) 26 (3.5) ck=creatine phosphokinase; urti=upper respiratory tract infection; uti=urinary tract infection. table 5. facial local tolerability assessments at week 12, scale 0 (none) to 3 (severe) facial local tolerability assessment,a n (%) fmx101 (n=737) vehicle foam (n=747) 0=none 1=mild 2= moderate 3= severe 0=none 1=mild 2= moderate 3= severe erythema 515 (82.7) 100 (16.0) 11 (1.8) 0 (0.0) 514 (82.5) 98 (15.7) 11 (1.8) 0 (0.0) dryness 568 (90.7) 53 (8.5) 5 (0.8) 0 (0.0) 550 (88.3) 68 (10.9) 4 (0.6) 1 (0.2) hyperpigmentationb 536 (85.6) 75 (12.0) 14 (2.2) 1 (0.2) 515 (82.7) 90 (14.4) 17 (2.7) 1 (0.2) skin peeling 607 (97.0) 18 (2.9) 1 (0.2) 0 (0.0) 587 (94.2) 33 (5.3) 2 (0.3) 1 (0.2) itching 588 (93.9) 30 (4.8) 7 (1.1) 1 (0.2) 577 (92.6) 40 (6.4) 6 (1.0) 0 (0.0) abased on safety population. bthe term hyperpigmentation was most commonly used to describe localized post-inflammatory darkening of the affected skin. safety summary • fmx101 4% was generally safe and well tolerated • treatment-emergent adverse events (teaes) were few in type and frequency; most were mild in severity • the most common adverse event in the study was upper respiratory tract infection, with similar frequency in the treatment arm (4.2%) and vehicle arm (3.5%) • there were no treatment-related serious adverse events, and there was low subject discontinuation due to a teae (tables 2 and 3) • cutaneous teaes were comparable in frequency in the fmx101 4% treatment group and vehicle group; the most common cutaneous ae (≥1% of subjects) was acne (table 4) – >95% of subjects had none or mild signs and symptoms at week 12 assessment of dermal tolerability (table 5) • in total, 5 subjects discontinued from study 22 due to a teae – 3 subjects for fmx101 4% 2 subjects for vehicle group conclusions • the results of the phase 3 study showed that fmx101 4% was safe and effective for the treatment of moderate-to-severe acne • the study met both co-primary end points of absolute change from baseline in inflammatory lesion count and proportion with iga treatment success at week 12 – significant reduction in number of both inflammatory and noninflammatory lesions at week 12 from baseline in fmx101 4% treatment group vs vehicle treatment group – significant improvement in iga treatment success at week 12 in fmx101 4% treatment group vs vehicle treatment group • the safety profile of fmx101 was found to be consistent with that determined from the 2 prior phase 3 studies (fx2014-04 and fx2014-05) fmx101 4% topical minocycline foam for the treatment of moderate-to-severe acne vulgaris: efficacy and safety from a phase 3 randomized, double-blind, vehicle-controlled study joseph raoof, md1, deirdre hooper, md2, angela moore, md3, martin zaiac, md4, tory sullivan, md5, leon kircik, md6, edward lain, md7, jasmina jankicevic, md8, iain stuart, phd8 1encino research center, encino, ca; 2delricht research, new orleans, la; 3arlington research center, arlington, tx; 4sweet hope research specialty, inc., miami lakes, fl; 5sullivan dermatology, north miami beach, fl; 6mount sinai hospital, new york, ny; 7austin institute for dermatology, austin, tx; 8foamix pharmaceuticals, inc, bridgewater, nj. disclosures this study was funded by foamix pharmaceuticals. dr. joseph raoof, dr. deirdre hooper, dr. martin zaiac, dr. tory sullivan, and dr. edward lain served as investigators for foamix. dr. angela moore is an investigator, consultant, and/or speaker for abbvie, aclaris, actavis, astellas, asubio, biofrontera, boehringer ingelheim, bristol-myers squibb, centocor, coherus, dermavant, dermira, eli lilly, foamix, galderma, incyte, janssen, leo, mayne, novartis, parexel, pfizer, therapeutics, verrica. dr. leon kircik is an investigator and consultant for foamix. dr. jasmina jankicevic is a consultant for foamix pharmaceuticals. dr. iain stuart is an employee of foamix pharmaceuticals. acknowledgment editorial support was provided by p-value communications. presented at the fall clinical dermatology conference; october 18-21, 2018; las vegas, nevada. results (cont.) ➢ at week 12, subjects treated with fmx101 4% had a statistically significantly greater reduction in the number of inflammatory lesions from baseline as compared with the vehicle treatment group, p<0.0001 (figure 2) figure 2. absolute change in inflammatory lesion count from baseline at week 12. 5 ‒ ‒ ancova, itt population, mi. ancova=analysis of covariance; ci=confidence interval; lsm=least squares mean; mi=multiple imputation. references 1. thiboutot dm, dreno b, abanmi, et al. practical management of acne for clinicians: an international consensus from the global alliance to improve outcomes in acne. j am acad dermatol. 2018; 78(2s1):s1-s23.e1. 2. zaenglein al, pathy al, schlosser bj, et al. guidelines of care for the management of acne vulgaris. j am acad dermatol. 2016. http://dx.doi.org/10.1016/j.jaad.2015.12.037. 3. schemer a, shiri j, mashiah j, et al. topical minocycline foam for moderate to severe acne vulgaris: phase 2 randomized double-blind, vehicle-controlled study results. j am acad dermatol. 2016;74(6):1251-1252. 4. gold ls, dhawan s, weiss j, et al. a novel minocycline foam for the treatment of moderate-to-severe acne vulgaris: results of two randomized, double-blind, phase 3 studies. j am acad dermatol. 2018 aug 27. epub ahead of print. ➢ at week 12, the proportion of subjects achieving iga treatment success in the fmx101 4% treatment group was statistically significantly higher than in the vehicle treatment group, p<0.0001 (figure 3) figure 3. iga treatment success at week 12. results (cont.) 6cochrane mantel-haenszel test, stratified by analysis center, itt population, mi 7 results (cont.) * ancova, itt population, observed cases ** ancova, itt population, mi p<0.05 figure 4: absolute change of non-inflammatory lesion count at week 12. ➢ at week 12, the absolute change in non-inflammatory lesion count in the fmx101 4% treatment group was statistically significantly greater than in the vehicle treatment group, p<0.05 (figure 4) ‒ ‒ results (cont.) 8 ancova, itt population, observed cases. *p≤.0001. figure 5. percentage change from baseline to week 12 in inflammatory lesions by visit ➢ the percentage reduction in inflammatory lesions was statistically significantly greater for fmx101 4% vs vehicle at all visits – week 3, 6, 9, and 12 (figure 5) skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 321 original research ampicillin use in acne cara barber bs1, kurt a ashack md2, joshua boulter bs1, richard j. ashack md3 1michigan state university college of human medicine, grand rapids, mi usa 2department of dermatology, university of illinois at chicago college of medicine, chicago, illinois 3dermatology associates of west michigan, grand rapids, michigan tetracycline antibiotics are considered firstline for acne vulgaris unresponsive to topical comedolytic agents, however, adverse events, allergies, and pregnancy represent contraindications to tetracyclines in addition to other alternative antiobiotics.1,2 in one author’s experience, ampicillin is beneficial in patients with inflammatory acne and has a favorable side effect profile. additionally, dr. ronald shore’s correspondence in 1973 abstract introduction: in one author’s experience, ampicillin is an effective alternative antibiotic for acne; however, current literature for ampicillin use in acne is scant. the objective of this study was to demonstrate the response of oral ampicillin in acne. methods: a retrospective analysis of 243 patients with acne vulgaris treated with ampicillin 500mg twice daily was conducted. the severity of acne (on a scale of 0 to 3) at the last visit was compared with baseline severity determined at the initial visit. results were analyzed using the paired samples t-test. results: the average severity of acne was reduced from 1.54 to 0.90 (p < 0.001). the average severity was reduced from 1.69 to 1.09 (p < 0.001) among men, and from 1.48 to 0.84 (p < 0.001) among woman. lastly, average severity was decreased from 1.67 to 1.12 (p < 0.001) in patients with nodulocystic acne, from 1.45 to 0.77 (p < 0.001) with inflammatory acne patients, and from 1.00 to 0.38 (p < 0.001) in patients with comedonal acne. limitations: this study was limited by its retrospective nature and analysis of a small patient population. additionally, a validated acne scoring system was not used due to provider documentation. conclusion: to conclude, ampicillin had a positive effect on our patient’s acne. introduction 2019 resident research competition – 2nd place skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 322 appreciated a similar effectiveness, specifically in mild to moderate inflammatory acne among young woman.3 while there are studies to support the use of amoxicillin2, data supporting the use of ampicillin in acne is scarce.4 this retrospective study was designed to assess the effectiveness of ampicillin for the treatment of acne in a private practice population. this study retrospectively analyzed 359 adults aged 18 to 70 years diagnosed with acne by a dermatologist, and who were treated with ampicillin 500mg twice daily between january 1, 2000 to july 31, 2018. patients without a severity description at the initial or final visit were excluded, resulting in 243 patients left for final analysis. this study was granted full irb approval by the michigan state university irb. ampicillin response was determined by one outcome variable: severity of acne as determined by the physician as none (0), mild (1), moderate (2), or severe (3) based on the total number of lesions, and whether the lesions are inflammatory or non‐ inflammatory. table i describes each of these variables. a single dermatologist recorded each variable at every visit. two researchers extracted data and determined the acne severity when unspecified with consensus or third researcher resolution of differences. analyses were performed using spss statistical software (version 25.0, spss inc., chicago, il). values for our outcome at the last visit (n = 243) were compared with baseline scores (n = 243) determined at the initial visit using a paired samples t-test. statistical significance was assumed with a p-value <0.05. characteristics of the study cohort are outlined in table 1. prior treatment before initiation of ampicillin included oral antibiotics (41.9%), topical therapies alone (20.2%), anti-hormonal therapy (4.9%), or a previous course of isotretinoin (13.6%). additionally, 6.2% of patients tried two or more antibiotics before starting ampicillin. (table 2) for determining the effectiveness of ampicillin therapy, outcome variables were compared before treatment and at the last documented patient visit. results are shown in figure 1. the average severity of acne was reduced from 1.54 to 0.90 (p < 0.001). the average severity was reduced from 1.69 to 1.09 (p < 0.001) among men, and from 1.48 to 0.84 (p < 0.001) among women. lastly, average severity was decreased from 1.67 to 1.12 (p < 0.001) in patients with nodulocystic acne, from 1.45 to 0.77 (p < 0.001) with inflammatory acne patients, and from 1.00 to 0.38 (p < 0.015) in patients with comedonal acne. seventy-nine (32.5%) of patients discontinued ampicillin therapy due to lack of efficacy or side effects. a majority of these patients went on to isotretinoin therapy or switched to an alternative antibiotic. ten patients (12.7%) went on to take spironolactone without antibiotics, and six (7.6%) preferred to only continue on topical therapies. (table 2) materials and methods statistical analysis results skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 323 figure 1. the effectiveness of ampicillin in acne. treatment data stratified by acne subtype. all reductions in acne severity were statistically significant. table 1. the effectiveness of ampicillin in acne. cohort statistics (uti = urinary tract infection) total no. of patients 243 male 61 (25.1%) female 182 (74.9%) mean age (years) 31.76 (14-70) location of acne before treatment face 158 (65%) face and chest 3 (1.2%) face and back 7 (2.8%) face, chest and back 75 (30.8%) severity of acne before treatment mild 117 (48.1%) moderate 122 (50.2%) severe 4 (1.6%) mean duration of treatment 22.4 months no. of adverse side effects noted 22 yeast infection 10 gi problems 9 uti 2 allergy 1 skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 324 table 2. treatments tried before, during, and after ampicillin therapy. a) topical therapies included: retinoids (187 patients), dapsone (25 patients), sodium sulfacetamide (43 patients), azaleic acid (13 patients), clindamycin (17 patients), erythromycin (1 patient), clindamycin/benzoyl peroxide (9 patients), benzoyl peroxide (5 patients). b) alternative antibiotics included: minocycline, doxycycline, sulfamethoxazole/trimethoprim, cephalexin, and cefadroxil treatments before ampicillin total number of patients topical therapya 49/243 (20.2%) minocycline 64/243 (25.5%) doxycycline 3/243 (1.2%) cephalexin 16/243 (6.6%) ciprofloxacin 1/243 (0.4%) cefadroxil 1/243 (0.4%) amoxicillin 2/243 (0.8%) amoxicillin/clavulanic acid 2/243 (0.8%) sulfamethoxazole/trimethoprim 15/243 (6.2%) oral contraceptive pills 5/243 (2.0%) spironolactone 7/243 (2.9%) isotretinoin 33/243 (13.6%) >2 antibiotics 15/243 (6.2%) treatments during ampicillin topical therapya 243/243 (100%) oral contraceptive pill 5/243 (2.0%) treatments after ampicillin 79/243 (32.5%) topical therapya 6/79 (7.6%) alternative antibioticb 32/79 (40.5%) spironolactone 10/79 (12.7%) isotretinoin 31/79 (39.2%) skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 325 this study demonstrates a positive response of ampicillin in all subtypes of acne vulgaris, with the most significant reduction among patients with inflammatory acne. additionally, subjects with comedonal and nodulocystic acne also demonstrated a significant improvement in acne severity. therefore ampicillin could be considered an effective alternative antibiotic for acne patients with a contraindication to first line therapies or experiencing unwanted adverse events. this includes children where tetracycline antibiotics are contraindicated. this antibiotic could also be considered in pregnant patients given its safety profile and pregnancy category b status, a similar recommendation as presented by guzman et al.2 limitations in this study are multiple, and included its retrospective nature and small sample size (n=243) . additionally, the study design was flawed with only a single global average severity measure was used by a single clinician at a single post treatment time. this hindered our ability to use a published and validated comprehensive acne severity scale. this also limits the comparison of this data to other studies using antibiotics for acne. it should also be noted that the mean duration of ampicillin use is much higher than what is currently practiced, given the increased push towards short term use of antibiotics for acne to reduce antibiotic resistance. therefore, only short courses of ampicillin are recommended for use in patients with acne. despite these limitations, our data still indicates a positive response of ampicillin in patients with inflammatory and nodulocystic acne. future studies are necessary to demonstrate the effectiveness of ampicillin compared to more common antimicrobial therapies. conflict of interest disclosures: none funding: none irb/consent: this study has full irb approval by the michigan state university irb. acknowledgements: we would like to acknowledge mark trottier, phd, of michigan state university college of human medicine for his guidance. corresponding author: kurt ashack, md university of illinois, college of medicine, department of dermatology college of medicine east building (cme), rm 380 808 south wood st, chicago, il 60612 312-413-7767 kashac2@uic.edu references: 1. farrah g , tan e. the use of oral antibiotics in treating acne vulgaris: a new approach. dermatol ther 2016;29:377-84. 2. guzman ak, choi jk , james wd. safety and effectiveness of amoxicillin in the treatment of inflammatory acne. int j womens dermatol 2018;4:174-5. 3. shore rn. usefulness of ampicillin in treatment of acne vulgaris. j am acad dermatol 1983;9:604-5. 4. zaenglein al, pathy al, schlosser bj, alikhan a, baldwin he, berson ds et al. guidelines of care for the management of acne vulgaris. j am acad dermatol 2016;74:945-73.e33. discussion mailto:kashac2@uic.edu skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 672 brief article diffuse large b-cell lymphoma in bilateral lower extremities leon kou, do1, kevyn niu, do2, austin wong, do1, aaron chen, do3, sid danesh, md1 1 danesh dermatology, beverly hills, ca 2 des moines university, college of osteopathic medicine, des moines, ia 3 department of dermatology, larkin community hospital, south miami, fl primary cutaneous b-cell lymphoma (pcbcl) is a special case of b-cell lymphoma that presents on the skin with no evidence of extracutaneous manifestations. diffuse large b-cell lymphoma, leg type (dlbcllt) is a rare variant that compromises only 20% of all pcbcls and commonly presents as primary cutaneous lesions on the lower extremities.1,2 there is no standard of care. early detection and treatment is essential as dlbcllt has a more aggressive clinical course compared to other types of pcbcl due to higher incidence of extracutaneous dissemination.2 despite the gross appearance, surgery is rarely used, instead r-chop (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) therapy with or without field radiotherapy is the preferred treatment.3 we present a rare case of bilateral dlbcllt in an 80-year-old male. an 80-year-old hispanic male was referred by his primary care physician to our dermatology clinic for 5 large bumps that first appeared on his left shin 8 months ago. the patient believed they started from a spider bite while working in the backyard. he notes the lesions are associated with pruritis, have increased in size, and expressed yellowish discharge. he was prescribed a regimen of cephalexin and sulfamethoxazole/trimethoprim by his primary doctor, without improvement. physical examination revealed multiple crusted tumors at the left mid shin and erythematous indurated plaques at the right calf (figure 1). abstract diffuse large b-cell lymphoma, leg type, is a rare variant of primary cutaneous b-cell lymphoma. it typically presents as rapidly enlarging solitary or multiple violaceous nodules on the lower extremities. even with adequate treatment with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, recurrence and systemic spread is common. timely treatment is necessary as this malignancy is associated with a more aggressive course than other variants of primary cutaneous bcell lymphoma and overall prognosis is poor. introduction case report skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 673 figure 1. erythematous indurated plaques at a) right medial calf and b) right posterior calf with c) and d) showing multiple crusted tumors at the left anterior shin shave biopsy, bacterial, and fungal culture was performed on the left shin. pathology reported dense hematolymphoid infiltrates in the dermis (figure 2). immunohistochemistry highlighted large lymphoma cells in sheets with positive staining for cd20, pax5, cd79a, bcl2, bcl6, mum1, cmyc, igm, with kappa light chain restriction and a ki67 proliferation index of > 90% (figure 3). the lymphocyte cells stained negative for cd10, igd, and tdt. fish analysis revealed a bcl6 translocation typically observed in diffuse large b-cell lymphoma (dlbcl). bacterial culture revealed heavy growth of enterococcus faecalis with sensitivity to ampicillin and vancomycin. fungal culture was negative with no fungal growth observed at 4 weeks. figure 2. hematoxylin and eosin stain showing dense hematolymphoid infiltrates in the dermis with an unaffected epidermis at a) 4x and b) 10x magnification a b skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 674 figure 3. positive immunohistochemical staining shown at 10x magnification for a) cd20 b) pax5 c) cd79a d) bcl2 e) bcl6 although the right leg was not biopsied, the timing and similarity in lesions strongly suggested the diagnosis of dlbcllt of the bilateral lower extremities. the patient was started on ampicillin and referred to oncology for further work up and treatment. he was placed on the r-chop chemotherapy regimen with close follow up. surgery was determined to be unnecessary at the time. most patients with dlbcllt present clinically with red or violaceous large nodules on the lower extremities that enlarge rapidly, as seen in our patient. metastasis to extracutaneous sites typically involve local lymph nodes and bone marrow; however, cns involvement has also been reported.4 differential diagnosis for dlbcllt includes infectious etiologies, variants of squamous cell carcinoma, and other types of lymphoma. dlbcllt is best separated from other forms of cutaneous lymphoma with histopathology and immunology. histologically, dlbcllt is comprised primarily of large b cells in sheets that diffusely infiltrate the dermis. a grenz zone usually separates the cancer cells from the epidermis; however, the cancer cells can occasionally extend to an ulcerated epidermis and even involve the subcutis.3,5 dlbcllt stains immunopositively for b-cell markers, cd 19, cd 20, cd 22, cd79a, and pax5.3 in contrast to other forms of pcbcl, a majority of dlbcllt cells express ki-67 and activated b-cell markers bcl2 and mum1, as seen in our patient.5 dlbcllt has an estimated 5 year survival rate of 41%, unlike other types of pcbcl with a more favorable prognosis.2,6 negative prognostic indicators include discussion a b c e d skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 675 lesions being present on the leg, presence of multiple cutaneous tumors, and age >75 years.6 bcl6 translocation, is the most common aberration in dlbcl; and translocations are another poor prognostic factor that was also seen in our patient.7 unfortunately, our patient has multiple negative prognostic indicators. furthermore, distant metastasis could not be ruled out at time of visit. thus, pet/ct will be vital in the workup to rule out metastasis. close monitoring and treatment by oncology will be essential for our patient’s long-term prognosis. current recommendations is rchop chemotherapy with or without radiation therapy; however, despite treatment, relapse and subsequent systemic spread is common.6,8 dlbcllt is a rare disease, with rapid onset and a poor prognosis. timely treatment is essential as even with adequate treatment, relapse and systemic spread is common. clinicians should be wary of rapidly enlarging violaceous nodules/tumors of the lower limbs and have a high suspicion for dlbcllt. conflict of interest disclosures: none funding: none corresponding author: leon kou, do 240 s. la cienega blvd beverly hills, ca 90211 phone: (909) 859-9885 email: k.leon@ucla.edu references: 1. willemze r, cerroni l, kempf w, et al. the 2018 update of the who-eortc classification for primary cutaneous lymphomas. blood. 2019;133(16):1703-1714. doi:10.1182/blood2018-11-881268 2. athalye l, nami n, shitabata p. a rare case of primary cutaneous diffuse large b-cell lymphoma, leg type. cutis. 2018;102(3):e31e34. 3. hristov ac. primary cutaneous diffuse large bcell lymphoma, leg type: diagnostic considerations. arch pathol lab med. 2012;136(8):876-881. doi:10.5858/arpa.20120195-ra 4. al-obaidi a, parker na, choucair k, lalich d, truong p. primary cutaneous diffuse large bcell lymphoma, leg type: a case report. cureus. 2020;12(6). doi:10.7759/cureus.8651 5. goyal a, leblanc re, carter jb. cutaneous bcell lymphoma. hematol oncol clin north am. 2019;33(1):149-161. doi:10.1016/j.hoc.2018.08.006 6. grange f, beylot-barry m, courville p, et al. primary cutaneous diffuse large b-cell lymphoma, leg type: clinicopathologic features and prognostic analysis in 60 cases. arch dermatol. 2007;143(9):1144-1150. doi:10.1001/archderm.143.9.1144 7. li s, wang z, lin l, et al. bcl6 rearrangement indicates poor prognosis in diffuse large b-cell lymphoma patients: a meta-analysis of cohort studies. j cancer. 2019;10(2):530-538. doi:10.7150/jca.25732 8. senff nj, noordijk em, kim yh, et al. european organization for research and treatment of cancer and international society for cutaneous lymphoma consensus recommendations for the management of cutaneous b-cell lymphomas. blood. 2008;112(5):1600-1609. doi:10.1182/blood-2008-04-152850 conclusion mailto:k.leon@ucla.edu bensal hp (bhp-410), a novel antimicrobial agent with activity against mrsa, vre, gram-negative mdros, yeasts, and dermatophytic fungi k. s. thomson1, g. k. thomson2, j. biehle3, a. deeb1, j. crawford1, r. herrera1, i. robledo4 and g. vázquez4 tm 1. bensal hp has an extremely broad spectrum of activity that is not compromised by mechanisms of antibiotic resistance occurring in contemporary multidrug resistant bacteria. 2. all gram-positive and gram-negative bacteria, yeasts, and filamentous fungi in this study were susceptible to the clinically used concentration of bensal hp (i.e. inhibited by undiluted ointment). 3. no resistance to bensal hp was detected. 4. bensal hp was rapidly bactericidal in time-kill studies with an isolate of pseudomonas aeruginosa and an isolate of mrsa. 5. further study is warranted to investigate its full clinical utility. 1 creighton university, omaha, ne, 2 university of louisville hospital, louisville, ky, 3 alegent creighton hospital, omaha, ne, 4 university of puerto rico, san juan, puerto rico references 1. moland, e. s., n. d. hanson, j. a. black, a. hossain, w. song, and k. s. thomson. 2006. prevalence of newer βlactamases in gram-negative clinical isolates collected in the united states from 2001 to 2 0 0 2 . j c l i n m i c r o b i o l 44:3318-24. 2. barry, a. l. 1991. procedures and theoretical considerations f o r te s t i n g a n t i m i c r o b i a l agents in agar media, p. 1-16. in v. lorian (ed.), antibiotics in laboratory medicine, 3rd ed. williams & wilkins, baltimore. 3. clinical and laboratory standards institute. 2013. performance standards for antimicrobial susceptibility testing; twenty-third informational supplement m100s23. clinical and laboratory standards institute, wayne, pa. background background: increasing multidrug resistance and a dwindling antibiotic pipeline have created a major global health crisis. little is known about the activity of topical agents against multidrug resistant organisms (mdros) or about their therapeutic or infection control relevance in meeting this challenge. with this in mind, a study was designed to assess the activity of a novel topical antimicrobial bhp-410 containing salicylic acid, benzoic acid and qrb-7 (oak bark extract) against a broad range of mdro's including mrsa, vre, esbl and carbapenemase-producing isolates. in addition its activity against selected isolates of mycobacterium fortuitum, nocardia brasiliensis, yeasts and filamentous fungi was also assessed. materials and methods: activity against 181 isolates comprising 12 bacterial species (5 gramnegative, 7 gram-positive), 3 yeast species, and 3 dermatophyte species was assessed. the 129 bacterial isolates included well characterized non-mdro and mdro isolates of enterobacteriaceae p. aeruginosa, a. baumannii, s. aureus, and enterococcus faecalis a n d r o u t i n e c l i n i c a l i s o l a t e s o f g r o u p a s t r e p t o c o c c i , propionibacterium acnes, m. fortuitum and n. brasiliensis. twenty one isolates of candida albicans, c. glabrata, cryptococcus neoformans and 30 isolates of trichophyton rubrum, t. tonsurans, and t. mentagrophytes were also tested. susceptibility to bhp-410 was determined by the cylinder diffusion and clsi agar dilution methods. bactericidal activity was assessed by time-kill methodology. results: in cylinder diffusion tests, all bacterial and fungal isolates were inhibited by bhp-410 and no resistance was detected. there was no apparent reduction in inhibition zone when comparing mdro-isolates to non-mdro (wild type) isolates. in mic tests non-mdro and mdro isolates were equally susceptible with all gram-positive isolates (including mrsa) inhibited by an 80-fold dilution of bhp-410. gram-negative isolates were all susceptible within a range of 40 to 80-fold dilutions. bhp-410 was rapidly bactericidal against p. aeruginosa and mrsa. conclusion: bhp-410 has an extremely broad spectrum of antimicrobial activity and is unaffected by the resistance mechanisms of mdros. further study is warranted to investigate its full clinical utility. the combination of increasing multidrug resistance and a dwindling antibiotic pipeline has created a major global health crisis in which there are few or no effective agents to treat bacterial infections. little is known about the activity of topical agents against multidrug resistant organisms (mdros) or about the therapeutic or infection control potential of topical agents in meeting this challenge. bensal hp (bhp-410) is a broad spectrum topical antimicrobial agent containing salicylic acid (30 mg/gm), benzoic acid (60 mg/gm), qrb-7 (oak bark extract, 30 mg/gm) and vehicle polyethylene glycol 400 and polyethylene glycol 3350. the current study was designed to assess its activity against a broad range of contemporary pathogens including mdros such as mrsa, vancomycin-resistant enterococcus (vre), mdr producers of ampc, extended spectrum βlactamase (esbl) and carbapenemase β -lactamases, mycobacterium fortuitum, nocardia brasiliensis, yeasts and filamentous fungi. abstract materials & methods test agent: bensal hp pdunhwhg�e\�(3,�+hdowk (&kduohvwrq�6&) organisms: in vitro activity was investigated against 184 bacterial and fungal isolates from the culture collections of creighton university, omaha, ne, the alegent creighton hospital microbiology laboratory, omaha, ne, and the university of louisville hospital microbiology lab, louisville, ky. the isolates were from u.s. and international sources and included well characterized non-mdro and mdro isolates of enterobacteriaceae (n=40), pseudomonas aeruginosa (n=11), acinetobacter baumannii (n=13), staphylococcus aureus (n=23) including mrsa and methicillin-susceptible s. aureus (mssa), and enterococcus faecalis (n=11) including vre. also tested were routine clinical isolates of group a streptococcus (s. pyogenes, n=12), propionibacterium acnes (n=1), mycobacterium fortuitum (n=10) and nocardia brasiliensis (n=10). the fungal isolates included candida albicans (n=10), c. glabrata (n=10), cryptococcus neoformans (n=1), trichophyton rubrum (n=12), t. tonsurans (n=10), and t. mentagrophytes (n=10). the mdros were previously characterized for resistance mechanisms by phenotypic, biochemical and molecular methods (1) and included isolates producing the esbls tem-52, shv esbls, oxa-45, ctx-m-1, ctxm-9, ctx-m-12, ctx-m-14, ctx-m-15, ctx-m-17, ctx-m-18, and ctx-m-19, chromosomal and plasmid-mediated ampc β-lactamases that included fox-like and cmy-2 enzymes, and carbapenemases of the imp, vim, kpc, and ndm families. especially challenging mdros included carbapenemase-producing isolates of p. aeruginosa and a. baumannii and p. aeruginosa isolates with upregulated mexab, mexef, and mexxy efflux pumps, and down-regulation of the oprd porin. investigations susceptibility was determined by the cylinder diffusion (2) and clsi agar dilution (3) methods. examples of cylinder diffusion tests are shown in figure 1. bactericidal activity was assessed by time-kill methodology following exposure of p. aeruginosa atcc 27853 and mrsa sa179 to concentrations of 1x and 4x the mic. results all isolates, bacterial and fungal, were inhibited by bensal hp. no resistance was detected. no mdro isolates exhibited cross resistance to bensal hp. that is, susceptibility was unaffected by the innate or acquired resistance mechanisms of the isolates. zone diameters were generally larger for gram-positive bacteria and filamentous fungi than for gram-negative bacteria (table 1). some mdros had larger inhibition zones than their wild type counterparts. representative isolates exhibiting this trend are shown in table 2. in mic tests with 73 selected isolates that included both mdros and non-mdros in each species tested, all gram-positive isolates were inhibited by an 80-fold dilution of bensal hp (mic = 0.375/ 0.75/ 0.375 mg/gm of salicylic acid/benzoic acid/qrb-7 respectively) and the gram-negative isolates were all susceptible to a 40-fold dilution (mic = 0.75/ 1.5/ 0.75 mg/gm of salicylic acid/benzoic acid/qrb-7 respectively), with most gram-negatives being susceptible to an 80-fold dilution (0.375/ 0.75/ 0.375 mg/gm). in time-kill tests, bhp-410 was rapidly bactericidal against p. aeruginosa atcc 27853 and mrsa sa179 at 4x the mic (1:20 dilution) with no regrowth occurring in the 24 hour incubation period (figures 2 and 3). results conclusions figure 1: representative cylinder diffusion tests figure 3: time-kill curves – pseudomonas aeruginosa figure 2: time-kill curves mrsa table 1: summary of cylinder diffusion tests table 2: representative examples of wild type strains with smaller inhibition zones than mdros methicillin-resistant staph. aureus pseudomonas aeruginosa escherichia coli common bacterial isolates common yeast & fungal isolates candida albicans trichophyton tonsurans trichophyton rubrum trichophyton mentagrophytes clinical resistance challenges select isolates enterococcus faecalis (vre) klebsiella pneumoniae (mdro) acinetobacter baumannii (kpc +) candida glabrata fc17posterepihealththomsonbensalhp.pdf poster presented at the 37th fall clinical dermatology conference | las vegas, nv | october 18-21, 2018 onset of action with glycopyrronium cloth in the treatment of primary axillary hyperhidrosis d. pariser,1 l. green,2 j. drew,3 r. gopalan,3 v. yan3 and d. glaser4 1eastern virginia medical school/virginia clinical research, inc., norfolk, va; 2george washington university school of medicine, washington, dc; 3dermira, inc., menlo park, ca; 4saint louis university, st. louis, mo introduction • hyperhidrosis, a condition characterized by sweat production exceeding that which is necessary to maintain normal thermal homeostasis, has an estimated us prevalence of 4.8% (~15.3 million people)1 • glycopyrronium tosylate (gt) is a topical anticholinergic recently approved by the us food and drug administration for primary axillary hyperhidrosis in patients ≥9 years of age (glycopyrronium cloth, 2.4%, for topical use)2 • the efficacy and safety of gt were established in two double-blind, vehicle (veh)-controlled phase 3 trials (atmos-1 [nct02530281], atmos-2 [nct02530294])2,3 • one of the outcomes in the phase 3 trials utilized a daily patient diary, allowing for a detailed by-day assessment of patient reported sweating severity, impact, and bothersomeness in the first week of treatment objective • to examine the timing of efficacy onset in the phase 3 double-blind trials, pooled results were evaluated daily for the first seven days of treatment and using weekly averages thereafter through week 4 (end of study) methods atmos-1 and atmos-2 study design • atmos-1 (sites in the us and germany) and atmos-2 (us sites only) were parallel-group, 4-week, double-blind phase 3 clinical trials – patients were randomized 2:1 to gt or veh once daily (figure 1) – eligible patients were ≥9 years of age (only patients aged ≥18 years were recruited at german sites), had primary axillary hyperhidrosis for ≥6 months, gravimetrically-measured sweat production of ≥50 mg/5 min in each axilla, axillary sweating daily diary (asdd) patient-reported sweating severity (item 2) score ≥4 (numeric scale 0-10), and hyperhidrosis disease severity scale (hdss) ≥3 – patients were excluded for history of a condition that could cause secondary hyperhidrosis or that could be exacerbated by trial medication, prior surgical procedure for hyperhidrosis, prior axillary treatment with an anti-hyperhidrosis medical device within 4 weeks of baseline, botulinum toxin within 1 year of baseline, or use of other treatments with anticholinergic activity within 4 weeks of baseline unless dosing was stable for ≥4 months prior to baseline figure 1. atmos-1/atmos-2 study design wk 0 randomization screening follow-up atmos-1 and atmos-2 arido randomized, double-blind treatment 44-week open-label extension patients aged ≥9 years with primary axillary hyperhidrosis • ≥6 months duration • sweat production of ≥50 mg/5 min in each axillaa • asdd item 2 score ≥4 • hdss grade 3 or 4 gt (n=229 | 234) gt 564 (86.6%) patients continued into arido vehicle (n=115 | 119) wk 4 wk 48 wk 49 co-primary efficacy endpoints at week 4: • asdd/asdd-c item 2 responder rate (≥4-point improvement) • absolute change in axillary sweat productiona secondary efficacy endpoints at week 4: • hdss responder rate (≥2-grade improvement) • sweat productiona response rate (≥50% reduction) other efficacy assessments at week 4: • change from baseline in cdlqi/dlqi agravimetrically measured asdd, axillary sweating daily diary; asdd-c, asdd-children; cdlqi, children’s dlqi; dlqi, dermatology life quality index; gt, topical glycopyrronium tosylate; hdss, hyperhidrosis disease severity scale efficacy and safety assessments • coprimary endpoints were – responder rate (≥4-point improvement from baseline) on item 2 (sweating severity) of the asdd – absolute change from baseline (cfb) in axillary sweat production (gravimetrically measured) at week 4 • the asdd is a newly developed 4-item patient-reported outcome (pro) – a child-specific version of the asdd (asdd-c) consisting of the first 2 items was utilized for patients ≥9 to <16 years – the asdd/asdd-c item 2 is a numeric rating scale (0 to 10) for assessing axillary sweating severity that has demonstrated validity, reliability and responsiveness to axillary hyperhidrosis treatment effect in clinical trials4 • a ≥4-point reduction in asdd/asdd-c item 2 correlates with a patient global impression of change rating of at least ‘moderately better’, consistent with clinically meaningful change – in addition to item 2 (sweating severity), asdd items assess impact (item 3) and bothersomeness (item 4) of sweating • items 3 and 4 are only administered to patients 16 years of age or older and are scored on a numeric scale from 0-4 • no response threshold is defined for items 3 and 4, so mean cfb was evaluated – all asdd item data were unique in that they were collected daily using an electronic diary throughout the trial, allowing for a detailed analysis of onset of effect within the first week of treatment • secondary efficacy endpoints included – hdss responder rate (≥2-grade improvement from baseline) – gravimetrically-measured sweat production responder rate (≥50% reduction from baseline; “grav-50”) – absolute cfb gravimetric sweat production • safety was assessed via treatment-emergent adverse events (teaes) analyses • pooled atmos-1/atmos-2 asdd/asdd-c item 2 scores were analyzed daily for the first seven days (post hoc) and weekly using averages for weeks 2, 3, and 4 (prespecified) – similar analyses were completed for asdd items 3 and 4 – asdd items (2, 3, and 4) required at least 4 days of data per week to calculate weekly averages • efficacy analyses were conducted for the intent-to-treat (itt) population (all randomized subjects dispensed study drug) and safety analyses were conducted for the safety population (all randomized patients who received ≥1 confirmed dose of study drug) • the markov chain monte carlo (mcmc) method for multiple imputation was used for missing efficacy data in the calculation of weekly scores; no data imputation was performed for the analysis of daily data • statistical comparison between gt and veh on the two coprimary endpoints was prespecified for week 4 – asdd/asdd-c item 2 responder rate was analyzed using the cochran-mantel-haenszel (cmh) test – absolute cfb in sweat production was analyzed using an analysis of covariance (ancova) model applied to the cfb data subsequent to ranking with factors for treatment group and analysis center, and baseline sweat production as a covariate – for secondary endpoints, a gated sequential procedure was used, first testing hdss responder rate then testing sweat production responder rate using cmh tests stratified by analysis center – post hoc analyses of asdd/asdd-c item 2 response for days 1 to 7 were analyzed descriptively results disposition, demographics, and baseline disease characteristics • in the pooled population of the double-blind trials, 463 patients were randomized to gt and 234 to vehicle; 426 (92.0%) and 225 (96.2%) completed the trials, respectively (figure 2) • patient demographics and baseline disease characteristics were similar across treatment arms and across studies (table 1) figure 2. patient disposition gt n=229 vehicle n=115 completed study n=208 (90.8%) completed study n=112 (97.4%) discontinued adverse event withdrew consent lost to follow-up noncompliance protocol violation other 3 1 1 1 0 0 0 discontinued adverse event withdrew consent lost to follow-up noncompliance protocol violation other 21 8 6 5 1 0 1 344 randomized atmos-1 gt n=234 vehicle n=119 completed study n=218 (93.2%) completed study n=113 (95.0%) discontinued adverse event withdrew consent lost to follow-up noncompliance protocol violation other 6 0 5 1 0 0 0 discontinued adverse event withdrew consent lost to follow-up noncompliance protocol violation other 16 9 5 0 0 1 1 353 randomized atmos-2 gt n=463 vehicle n=234 completed study n=426 (92.0%) completed study n=225 (96.2%) discontinued adverse event withdrew consent lost to follow-up noncompliance protocol violation other 9 1 6 2 0 0 0 discontinued adverse event withdrew consent lost to follow-up noncompliance protocol violation other 37 17 11 5 1 1 2 697 randomized pooled gt, topical glycopyrronium tosylate table 1. patient demographics and baseline disease characteristics atmos-1 atmos-2 pooled vehicle (n=115) gt (n=229) vehicle (n=119) gt (n=234) vehicle (n=234) gt (n=463) demographics age (years), mean ± sd 34.0 ± 13.1 32.1 ± 11.2 32.8 ± 11.2 32.6 ± 10.9 33.4 ± 12.2 32.3 ± 11.0 age group, n (%) ≥16 years 109 (94.8) 224 (97.8) 109 (91.6) 223 (95.3) 218 (93.2) 447 (96.5) male, n (%) 55 (47.8) 99 (43.2) 59 (49.6) 113 (48.3) 114 (48.7) 212 (45.8) white, n (%) 94 (81.7) 182 (79.5) 102 (85.7) 192 (82.1) 196 (83.8) 374 (80.8) baseline disease characteristics sweat production (mg/5 min), mean ± sd (median) 170.3 ± 164.2 (112.6) 182.9 ± 266.9 (122.1) 181.8 ± 160.1 (116.7) 162.3 ± 149.5 (126.8) 176.2 ± 161.9 (114.8) 172.5 ± 215.7 (124.6) asdd/asdd-c item 2 (sweating severity), mean ± sd 7.1 ± 1.7 7.3 ± 1.6 7.2 ± 1.6 7.3 ± 1.6 7.2 ± 1.6 7.3 ± 1.6 asdd item 3 (impact) n=109 n=224 n=109 n=223 n=218 n=447 mean ± sd 2.2 ±0.9 2.4 ±0.9 2.3 ±1.0 2.5 ±0.8 2.2 ±0.9 2.4 ±0.9 asdd item 4 (bothersomeness) n=109 n=224 n=109 n=223 n=218 n=447 mean ± sd 2.4 ±0.9 2.6 ±0.8 2.5 ±0.9 2.7 ±0.7 2.5 ±0.9 2.7 ±0.8 hdss, n (%) grade 3 grade 4 84 (73.0) 31 (27.0) 133 (58.1) 96 (41.9) 71 (59.7) 47 (39.5) 144 (61.5) 90 (38.5) 155 (66.2) 78 (33.3) 277 (59.8) 186 (40.2) dlqi (for patients >16 years of age), mean ± sd n=108 10.1 ± 5.9 n=220 12.1 ± 6.5 n=107 11.2 ± 5.8 n=218 11.6 ± 5.7 n=215 10.6 ± 5.9 n=438 11.9 ± 6.1 cdlqi (for patients ≤16 years of age),mean ± sd n=7 6.9 ± 3.3 n=8 8.5 ± 6.5 n=12 9.5 ± 6.5 n=16 10.6 ± 5.1 n=19 8.5 ± 5.6 n=24 9.9 ± 5.5 asdd, axillary sweating daily diary; cdlqi, children’s dlqi; dlqi, dermatology life quality index; gt, topical glycopyrronium tosylate; hdss, hyperhidrosis disease severity scale; itt, intent-to-treat; sd, standard deviation efficacy: co-primary endpoints • a significant advantage for gt over veh was observed on both co-primary endpoints (p<0.001; asdd/asdd-c item 2 responder rate (≥4-point improvement from baseline) and absolute change in sweat production at week 4 in the pooled population)3 efficacy: daily and weekly findings (asdd/asdd-c item 2) • for the analyses evaluating daily asdd/asdd-c item 2 responder rate over the first 7 days: – a markedly greater proportion of gt patients achieved ≥4-point asdd/asdd-c item 2 improvement from baseline starting on day 2 vs veh patients: day 1 (1.7% vs 0.9%) and day 2 (24.2% vs 11.5%) (figure 3) – an increasingly higher proportion of gt-treated patients achieved asdd/asdd-c item 2 response versus veh throughout the remaining days of week 1 (figure 3) • after day 7, the proportion of asdd/asdd-c item 2 responders continued to increase with gt versus veh through the end of the trial, and was statistically significant at week 4 (59.5% vs 27.6%; p<0.001; co-primary endpoint) (figure 3) figure 3. daily (days 0-7) and weekly asdd/asdd-c item 2 responder rate (≥4-point improvement in sweating severity) 50 60 10 20 30 40 70 0p er ce nt ag e of p at ie nt s w ith ≥ 4p oi nt im pr ov em en t o n a s d d it em 2 days weeks 0 1 2 3 4 5 6 7 2 3 4 gt (n=463) vehicle (n=234) 0.9 16.2 11.5 17.1 18.4 18.8 16.2 19.0 26.4 27.6 1.7 32.4 24.2 36.3 45.6 50.5 57.1 59.5 42.8 39.1 pooled itt population; ** p<0.001 at week 4 (statsitical comparisons not performed for days 1-7 or weeks 1-3); no imputation of missing values for days 1-7; mcmc used to impute missing data for weekly values asdd, axillary sweating daily diary; gt, topical glycopyrronium tosylate; itt, intent to treat; mcmc, markov chain monte carlo; veh, vehicle efficacy: daily and weekly findings (asdd items 3 and 4) • mean change from baseline on asdd items 3 (impact) and 4 (bothersomeness) showed separation in favor of gt relative to veh in the first seven days and through week 4 (figure 4a and b) figure 4. daily (days 0-7) and weekly change from baseline in asdd item 3 (impact) and item 4 (bothersomeness) -0.2 0 -1.2 -1.0 -0.6 -0.8 -0.4 -1.4 -1.6 m ea n c ha ng e fr om b as el in e a s d d it em 3 days weeks 0 1 2 3 4 5 6 7 2 3 4 gt (n=447) vehicle (n=218) gt (n=447) vehicle (n=218) a. asdd item 3 (impact) im provem ent -0.2 0 0.2 -1.2 -1.0 -0.6 -0.8 -0.4 -1.4 -1.6 -1.8 m ea n c ha ng e fr om b as el in e a s d d it em 4 days weeks 0 1 2 3 4 5 6 7 2 3 4 b. asdd item 4 (bothersomeness) im provem ent 0 -0.5 -0.4 -0.5 -0.7 -0.6 -0.6 -0.7 -0.9 -0.9 0.1 -0.5 -0.3 -0.6 -0.7 -0.7 -0.6 -0.8 -0.9 -1.0 -0.1 -1.1 -0.8 -1.2 -1.3 -1.4 -1.5 -1.6-1.3 -1.2 0 -1.3 -0.9 -1.3 -1.5 -1.6 -1.7 -1.8-1.5 -1.4 pooled itt population; no imputation of missing values for days 1-7; mcmc used to impute missing data for weekly values. asdd item 3: during the past 24 hours, to what extent did your underarm sweating impact your activities? (0=not at all; 4=an extreme amount) asdd item 4: during the past 24 hours, how bothered were you by your underarm sweating? (0=not at all bothered; 4=extremely bothered) asdd, axillary sweating daily diary; gt, topical glycopyrronium tosylate; itt, intent-to-treat; mcmc, markov chain monte carlo; veh, vehicle efficacy: weekly findings (hdss responder rate, grav-50 responder rate, and median change gravimetric sweat production) • the asdd items were the only efficacy data collected daily during the trials; however, similar results were observed for additional efficacy assessments when evaluating patient outcomes by week – for hdss and sweat production, the proportion of responders at week 4 was significantly higher for gt versus vehicle (p<0.001 for each outcome in both trials),3 a difference occurring as early as week 1 (figures 5 and 6; statistical comparisons not performed at weeks 1-3) – absolute reduction from baseline in sweat production was significantly greater with gt compared with veh at week 4 (co-primary endpoint; p<0.001 based on ls mean change), and separation was observed as early as week 1 (statistical comparisons not performed for weeks 1-3; figure 7) figure 5. hdss responder ratea weeks 1-4 100 20 40 60 80 0 h d s s r es po nd er s (% ) week 0 1 2 3 4 gt (n=463) vehicle (n=234) 13.3 24.8 21.5 25.7 37.1 56.3 47.5 59.1 pooled itt population; aat least a 2-grade improvement from baseline; ** p<0.001 at week 4 (statstical comparisons not performed for weeks 1-3); mcmc used to impute missing values. gt, topical glycopyrronium tosylate; hdss; hyperhidrosis disease severity scale; itt, intent-to-treat; mcmc, markov chain monte carlo figure 6. grav-50a responder rate weeks 1-4 100 20 40 60 80 0 s w ea t p ro du ct io n r es po nd er s (% ) week 0 1 2 3 4 gt (n=463) vehicle (n=234) 42.5 53.8 47.0 53.2 69.6 71.372.1 74.9 pooled itt population; aat least a 50% reduction in gravimetrically measured sweat production (average of both axillae); ** p<0.001 mcmc used to impute missing values; no statstical comparisons performed gt, topical glycopyrronium tosylate; itt, intent-to-treat; mcmc, markov chain monte carlo figure 7. absolute reduction in sweat production from baseline (weeks 1-4) week 1 gt vehicle -70.4 -44.9 week 2 gt vehicle -78.0 -55.0 week 3 gt vehicle -74.7 -58.5 week 4 gt vehicle -79.8** -61.8 0 -90 -40 -50 -60 -70 -30 -20 -10 -80m ed ia n a bs ol ut e c ha ng e fr om b as el in e (m g/ 5 m in ) median reduction in sweat productiona n value (interquartile range) n=463 (-135.67, -39.01) n=234 (-94.11, -8.99) n=463 (-42.7 -39.12) n=234 (-107.14, -21.66) n=463 (-140.57 -39.17) n=234 (-117.69, -24.85) n=463 (-146.35 -42.85) n=234 (-113.9, -24.35) pooled itt population; **p<0.001 at week 4 (statstical comparisons not performed for weeks 1-3) based on ls mean change from baseline, amcmc used to impute missing values gt, topical glycopyrronium tosylate; mcmc, markov chain monte carlo safety • overall, gt was well tolerated, and most adverse events were mild to moderate in severity, and infrequently led to discontinuation (table 2; figure 2) • the majority of teaes reported in the gt group were related to anticholinergic activity, and the most frequently reported anticholinergic teaes in gt-treated patients were dry mouth (24.2%), mydriasis (6.8%), and urinary hesitation (3.5%) (table 2) table 2. safety overview (safety population) pooled vehicle (n=232) gt (n=459) teaes, n (%) any 75 (32.3) 257 (56.0) drug-related 38 (16.4) 179 (39.0) seriousa 0 2 ( 0.4) d/c due to teae, n (%) 1 ( 0.4) 17 ( 3.7) deaths, n (%) 0 0 teaes by intensity, n (%) mild 53 (22.8) 170 (37.0) moderate 22 ( 9.5) 83 (18.1) severe 0 4 ( 0.9) anticholinergic teaes reported in >2% of patients,b n (%) dry mouth 13 (5.6) 111 (24.2) mydriasis 0 31 ( 6.8) urinary hesitation 0 16 ( 3.5) dry eye 1 (0.4) 11 ( 2.4) vision blurred 0 16 ( 3.5) nasal dryness 1 (0.4) 12 ( 2.6) constipation 0 9 ( 2.0) urinary retention 0 7 ( 1.5) aserious teaes: atmos-1: moderate unilateral mydriasis, considered related to study drug; atmos-2: moderate dehydration, considered not related to study drug b >2% in any individual treatment arm in atmos-1 or atmos-2 d/c, discontinuation; gt, topical glycopyrronium tosylate; teae, treatment-emergent adverse event conclusions • a notably higher proportion of patients reporting reductions in sweating severity (asdd item 2), and larger improvements from baseline for impact (asdd item 3) and bothersomeness (asdd item 4) were observed in gt compared to veh as early as day 2 of treatment (post hoc analyses), consistent with an early onset of action • efficacy of gt (as assessed via responder rates for asdd item 2, hdss, grav-50, and absolute change from baseline in sweat production; prespecified analyses) generally increased throughout the trial – the highest proportion of patients achieved response thresholds at week 4 across multiple measures • daily gt treatment over 4 weeks was generally well tolerated in patients ≥9 years of age with primary axillary hyperhidrosis • the availability of topical, once-daily gt provides a noninvasive, effective treatment option for primary axillary hyperhidrosis2 references 1. doolittle et al. arch dermatol res. 2016;308(10):743-749. 2. qbrexzatm (glycopyrronium) cloth [prescribing information]. dermira, inc., menlo park, ca. 2018. 3. glaser et al. journal of the american academy of dermatology. 2018 (in preparation). 4. glaser et al. poster presented at 13th annual maui derm for dermatologists; 2017; maui, hi. acknowledgements these studies were funded by dermira, inc. medical writing support was provided by prescott medical communications group (chicago, il) with financial support from dermira, inc. disclosures dmp: consultant and investigator for dermira, inc. lg: investigator for brickell; advisory board member and investigator for dermira. jd: employee of dermira, inc. rg: employee of dermira, inc. vy: employee of dermira, inc. dag: consultant and investigator for dermira, poster presented at the 36th fall clinical dermatology conference | las vegas, nv | october 12-15, 2017 burden of axillary hyperhidrosis using a patient-reported outcome measure to assess impact on activities and bothersomeness david m. pariser,1 adelaide a. hebert,2 janice drew,3 john quiring,4 dee anna glaser5 1eastern virginia medical school and virginial clinical research, inc., norfolk, va; 2uthealth mcgovern medical school at houston, houston, tx; 3dermira, inc., menlo park, ca; 4qst consultations, allendale, mi; 5saint louis university, st. louis, mo introduction • hyperhidrosis, which is estimated to affect 4.8% of the us population or approximately 15.3 million people, is associated with considerable impairment in work productivity, social activities, emotional well-being, and personal relationships1,2 • topical glycopyrronium tosylate (gt; formerly drm04), a cholinergic receptor antagonist, has been assessed in 2 replicate randomized phase 3 clinical trials (atmos-1 and atmos-2) for the treatment of primary axillary hyperhidrosis in patients ≥9 years of age; the primary efficacy and safety results of these studies have been previously reported3 • patient-reported outcomes (pros) from these pivotal trials were also assessed using the 4-item axillary sweating daily diary (asdd),4 6 weekly impact items, and the single-item patient global impression of change (pgic), that were developed according to current regulatory standards objective • to evaluate the burden of disease associated with primary axillary hyperhidrosis utilizing pro measures reported at baseline for patients who participated in atmos-1 and atmos-2 methods atmos-1 and atmos-2 study design • atmos-1 (nct02530281; sites in the us and germany) and atmos-2 (nct02530294; us sites only) were parallel-group, 4-week, double-blind, phase 3 clinical trials in which patients with primary axillary hyperhidrosis were randomized (2:1) to gt or vehicle (figure 1) • for the purposes of this analysis, data from the gt and vehicle groups from each study have been pooled • eligible patients were ≥9 years of age and had primary axillary hyperhidrosis for ≥6 months, with gravimetrically-measured sweat production of ≥50 mg/5 min in each axilla, asdd axillary sweating severity item (item 2) score ≥4, and hyperhidrosis disease severity scale (hdss) grade 3 or 4 • patients were excluded for history of a condition that could cause secondary hyperhidrosis; prior surgical procedure or treatment with a medical device for axillary hyperhidrosis; treatment with iontophoresis within 4 weeks or treatment with botulinum toxin for axillary hyperhidrosis within 1 year; axillary use of nonprescription antiperspirant within 1 week or prescription antiperspirant within 2 weeks; new or modified psychotherapeutic medication regimen within 2 weeks; treatment with medications having systemic anticholinergic activity, centrally acting alpha-2 adrenergic agonists, or beta-blockers within 4 weeks unless dose had been stable ≥4 months and was not expected to change; and/or conditions that could be exacerbated by study medication figure 1. study design week 0 week 4 atmos-1 and atmos-2 target recruitment: 330 patients randomized 2:1 gt vehicle burden of disease measures • axillary hyperhidrosis patient measures (ahpm) – the asdd consists of 4 items and was used for patients ≥16 years; patients <16 years of age completed a modified, child-specific, 2-item version called the asdd-c (table 1) – patients ≥16 years were additionally asked to complete 6 weekly impact items and a single-item patient global impression of change (pgic; table 1) • the burden of disease associated with primary axillary hyperhidrosis was summarized by descriptive statistics in the intent-to-treat (itt) population (all randomized subjects who were dispensed study drug) based on: – mean score at baseline on asdd axillary sweating severity item (item 2; all patients) and items addressing the impact and bother of sweating (items 3 and 4, respectively; patients ≥16 years of age); baseline was defined as the average of ≥4 days of data in the most recent 7 days prior to randomization – mean score at baseline for weekly impact items (patients ≥16 years of age); baseline was defined as the last available record prior to day 1 • an additional analysis was performed to assess the proportion of patients with moderate-to-severe axillary sweating, impact, and bother, defined as scores of 9 or 10 on asdd item 2 and scores of 3 or 4 on asdd items 3 and 4, respectively table 1. axillary hyperhidrosis patient measures (ahpm)a axillary sweating daily diary (asdd)b instructions: the questions in the diary are designed to measure the severity and impact of any underarm sweating you have experienced within the previous 24 hour period, including nighttime hours. while you may also experience sweating in other locations on your body, please be sure to think only about your underarm sweating when answering these questions. please complete the diary each evening before you go to sleep. item 1 [gatekeeper] during the past 24 hours, did you have any underarm sweating? yes/no when item 1 is answered “no,” item 2 is skipped and scored as zero item 2 during the past 24 hours, how would you rate your underarm sweating at its worst? 0 (no sweating at all) to 10 (worst possible sweating) item 3 during the past 24 hours, to what extent did your underarm sweating impact your activities? 0 (not at all), 1 (a little bit), 2 (a moderate amount), 3 (a great deal), 4 (an extreme amount) item 4 during the past 24 hours, how bothered were you by your underarm sweating? 0 (not at all bothered), 1 (a little bothered), 2 (moderately bothered), 3 (very bothered), 4 (extremely bothered) axillary sweating daily diary-children (asdd-c)c instructions: these questions measure how bad your underarm sweating was last night and today. please think only about your underarm sweating when answering these questions. please complete these questions each night before you go to sleep. item 1 [gatekeeper] thinking about last night and today, did you have any underarm sweating? yes/no when item 1 is answered “no,” item 2 is skipped and scored as zero item 2 thinking about last night and today, how bad was your underarm sweating? 0 (no sweating at all) to 10 (worst possible sweating) weekly impact itemsb instructions: please respond “yes” or “no” to each of the following questions. a. during the past 7 days, did you ever have to change your shirt during the day because of your underarm sweating? yes/ no b. during the past 7 days, did you ever have to take more than 1 shower or bath a day because of your underarm sweating? yes/ no c. during the past 7 days, did you ever feel less confident in yourself because of your underarm sweating? yes/ no d. during the past 7 days, did you ever feel embarrassed by your underarm sweating? yes/ no e. during the past 7 days, did you ever avoid interactions with other people because of your underarm sweating? yes/ no f. during the past 7 days, did your underarm sweating ever keep you from doing an activity you wanted or needed to do? yes/ no patient global impression of change (pgic) itemb overall, how would you rate your underarm sweating now as compared to before starting the study treatment? 1 (much better), 2 (moderately better), 3 (a little better), 4 (no difference), 5 (a little worse), 6 (moderately worse), 7 (much worse) aasdd/asdd-c item 2 is a validated pro measure bfor use in patients ≥16 years of age cfor use in patients ≥9 to < 16 years of age results • a total of 697 patients were randomized and were asked to complete asdd/asdd-c items 1 and 2; 665 patients were ≥16 years of age and were asked to complete items addressing the impact and bother of sweating (items 3 and 4, respectively), and the weekly impact items • demographics and baseline disease characteristics were similar between studies (table 2) table 2. baseline demographic and disease characteristics (itt populations) atmos-1 (n=344) atmos-2 (n=353) demographics age (years), mean ± sd 32.7 ± 11.9 32.6 ±11.0 age group, n (%) <16 years ≥16 years 11 ( 3.2) 333 (96.8) 21 ( 5.9) 332 (94.1) male, n (%) 154 (44.8) 172 (48.7) white, n (%) 276 (80.2) 294 (83.3) bmi (kg/m2), mean ± sd 27.5 ± 5.5 27.7 ± 5.2 baseline disease characteristics years with primary axillary hyperhidrosis, mean ± sd 14.5 ± 10.7 16.5 ±10.7 sweat production (mg/5 min)a, mean ± sd 178.7 ± 237.4 168.9 ± 153.2 hdssb, n (%) grade 3 grade 4 217 (63.1) 127 (36.9) 215 (60.9) 137 (38.8) asdd item 2c, mean ± sd 7.2 ± 1.7 7.3 ± 1.6 agravimetrically measured bhdss grade 3 or 4 was an inclusion criteria for the study caverage of daily records from the 7 days prior to date of first dose; a minimum of 4 days was required to compute the average asdd, axillary sweating daily diary; bmi, body mass index; hdss, hyperhidrosis disease severity score; itt, intent-to-treat • at baseline in atmos-1 and atmos-2, the mean ± sd asdd/asdd-c axillary sweating severity item (item 2) scores were 7.2 ± 1.6 and 7.3 ± 1.6, respectively – in each trial, more than half of all patients reported weekly average scores ≥7 before randomization, indicating that patients considered their sweating to be moderate or severe at baseline (figure 2) – 16.0% and 19.3% of patients rated the severity of their axillary sweating as 9 or 10 in atmos-1 and atmos-2, respectively, indicating severe axillary hyperhidrosis at baseline (figure 2) figure 2. proportion of patients reporting moderate-to-severe axillary sweating at baseline (asdd/asdd-c item 2 scores) 59.3% 59.8% average score ≥7 16.0% 19.3% average score 9 or 10 atmos-1 (n=344) atmos-2 (n=353) 80 100 60 40 20 0 b as el in e a s d d it em 2 s co re s, % o f p at ie nt s data are representative of the intent-to-treat (itt) population asdd item 2: during the past 24 hours, how would you rate your underarm sweating at its worst? 0 (no sweating at all) to 10 (worst possible sweating) asdd-c item 2: thinking about last night and today, how bad was your underarm sweating? 0 (no sweating at all) to 10 (worst possible sweating) asdd, axillary sweating daily diary; asdd-c, asdd-children • at baseline in atmos-1 and atmos-2, mean ± sd asdd item 3 (impact of axillary sweating) scores were 2.3 ± 0.9 and 2.4 ± 0.9, respectively – in each trial, approximately 70% of patients ≥16 years of age reported scores ≥2 on asdd item 3, indicating that their daily activities were at least moderately affected by axillary hyperhidrosis at baseline (figure 3) – 26.2% and 29.7% of patients were severely impacted by axillary sweating in atmos-1 and atmos-2, respectively, having reported scores of 3 or 4 at baseline (figure 3) figure 3. proportion of patients reporting moderate-to-severe impact of axillary sweating at baseline (asdd item 3 scores) 69.4% 71.7% average score ≥2 26.2% 29.7% average score 3 or 4 atmos-1 (n=344) atmos-2 (n=353) 80 100 60 40 20 0 b as el in e a s d d it em 3 s co re s, % o f p at ie nt s data are representative of the intent-to-treat (itt) population asdd item 3: during the past 24 hours, to what extent did your underarm sweating impact your activities? 0 (not at all), 1 (a little bit), 2 (a moderate amount), 3 (a great deal), 4 (an extreme amount) asdd, axillary sweating daily diary • at baseline in atmos-1 and atmos-2, the mean ± sd asdd item 4 (bother of axillary sweating) scores were 2.6 ± 0.9 and 2.6 ± 0.9, respectively – in each trial, >75% of patients ≥16 years of age reported scores ≥2 on asdd item 4, indicating that they were at least moderately bothered by axillary sweating at baseline (figure 4) – 37.5% and 40.1% of patients were severely bothered by axillary sweating in atmos-1 and atmos-2, respectively, having reported scores of 3 or 4 at baseline (figure 4) figure 4. proportion of patients reporting moderate-to-severe bother of axillary sweating at baseline (asdd item 4 scores) 77.8% 77.4% average score ≥2 37.5% 40.1% average score 3 or 4 atmos-1 (n=344) atmos-2 (n=353) 80 100 60 40 20 0 b as el in e a s d d it em 4 s co re s, % o f p at ie nt s data are representative of the intent-to-treat (itt) population asdd item 4: during the past 24 hours, how bothered were you by your underarm sweating? 0 (not at all bothered), 1 (a little bothered), 2 (moderately bothered), 3 (very bothered), 4 (extremely bothered) asdd, axillary sweating daily diary • at baseline, the majority of patients who were ≥16 years of age answered ‘yes’ to questions asking if their underarm sweating affected their actions or emotions (weekly impact items) during the past week (figure 5) – notably, more than 96% of patients reporting feeling embarrassed figure 5. proportion of patients answering ‘yes’ to weekly impact items 83.9% 87.3% a. needed to change shirt during the day 60.4% 54.0% b. needed ≥1 shower/bath a day 89.5% 93.0% c. felt less confident 96.7% 96.3% d. felt embarrassed 68.1% 65.0% e. avoided interactions 58.2% 58.3% f. kept from doing an activity atmos-1 (n=304) atmos-2 (n=300) 80 100 60 40 20 0 % o f p at ie nt s an sw er in g “y es ” to w ee kl y im pa ct it em s data are representative of the intent-to-treat (itt) population conclusions • at baseline, more than half of all patients who participated in atmos-1 and atmos-2 reported that their sweating was at least a 7 on an 11-point scale where 0 represents no sweating and 10 represents worst possible sweating • in patients who were ≥16 years of age, axillary hyperhidrosis at least moderately affected their daily activities and was considered at least moderately bothersome – approximately 1 in 5 patients reported experiencing severe axillary sweating – approximately 1 in 3 reported feeling severely impacted and/or bothered by their sweating • on a weekly basis, the majority of patients who were ≥16 years of age reported being markedly impacted by their excess sweating, with most having to avoid interactions or take additional measures (ie, showering/bathing more than once a day; changing shirts during the day) to manage their excessive sweating; more than 90% of patients were less confident or embarrassed by sweating • these findings are consistent with previous reports that hyperhidrosis is associated with a substantial disease burden; as such, safe and effective new treatment options are needed for this disease references 1. doolittle et al. arch dermatol res. 2016; 308 (10):743-9. 2. hamm. dermatology. 2006;212:343-53. 3. pariser et al. poster presented at: the 25th european academy of dermatology and venereology congress; september 28-october 2, 2016; vienna, austria. 4. pariser et al. poster presented at: 13th annual maui derm for dermatologists; march 20-24, 2017; maui, hi. acknowledgements the authors would like to thank sheri fehnel, dana dibenedetti, and lauren nelson, from rti health solutions, as well as diane ingolia and christine conroy, from dermira, inc., for their work developing the pro questionnaire. these studies were funded by dermira, inc. medical writing support was provided by prescott medical communications group. all costs associated with development of this abstract were funded by dermira, inc. author disclosures dmp: consultant and investigator for dermira, inc.; ah: consultant for dermira, inc.; employee of the university of texas medical school, houston, which received compensation from dermira, inc. for study participation; jd: employee of dermira, inc; jq: employee of qst consultations; dag: consultant and investigator for dermira, inc. . fc17posterdermirapariserburdenofhyperhidrosis.pdf acknowledgements: medical writing support was provided by prescott medical communications group (chicago, il) with financial support from ortho dermatologics; ortho dermatologics is a division of bausch health us, llc • presented at winter clinical 2021 • january 16-24, 2021 • virtual synopsis � acne is common among adolescents, occurring in 85% of this population1 � the overall prevalence of acne tends to decrease with age; however, acne can persist throughout adulthood, more often in females than males2,3 � in addition, older age and female sex are associated with greater negative impacts on quality of life4 � the first lotion formulation of tazarotene 0.045%, developed using a novel polymeric emulsion technology, was efficacious and well tolerated in two phase 3 studies of patients ≥9 years of age with moderate-to-severe acne (nct03168334 and nct03168321)5 objective � to assess the effects of age on efficacy and safety of tazarotene 0.045% lotion in females with moderateto-severe acne methods � in two phase 3 randomized, double-blind, vehiclecontrolled studies, eligible participants aged ≥9 years with moderate-to-severe acne were randomized 1:1 to tazarotene 0.045% lotion or vehicle once daily for 12 weeks • cerave® hydrating cleanser and cerave® moisturizing lotion (l’oreal, ny) were provided as needed for optimal moisturization/cleaning of the skin � data from these studies were pooled and analyzed post hoc from female participants who were categorized by age: 13–19 years, 20–29 years, and 30+ years � efficacy assessments included mean reductions in inflammatory/noninflammatory lesion counts and percentage of participants achieving treatment success (≥2-grade reduction in evaluator’s global severity score [egss] and rating of ‘clear’ or ‘almost clear’) � treatment-emergent adverse events (teaes) and cutaneous safety/tolerability were also assessed figure 1. lesion reductions by age group and visit (itt population, pooled) -36.3% -45.1% -53.2% -36.1% -52.1% -61.0% -70% -60% -50% -40% -30% -20% -10% 0% baseline week 4 week 8 week 12 vehicle lotion (n=241) tazarotene 0.045% lotion (n=238) 20–29 years13–19 years ** -41.4% -51.0% -58.8% -35.5% -50.8% -60.2% -70% -60% -50% -40% -30% -20% -10% 0% baseline week 4 week 8 week 12 vehicle lotion (n=71) tazarotene 0.045% lotion (n=72) 30+ years -30.5% -40.8% -49.7% -29.7% -47.2% -59.3% -70% -60% -50% -40% -30% -20% -10% 0% baseline week 4 week 8 week 12 vehicle lotion (n=199) tazarotene 0.045% lotion (n=192) * ** -29.4% -37.5% -48.3%-37.7% -50.3% -60.0% -70% -60% -50% -40% -30% -20% -10% 0% baseline week 4 week 8 week 12 vehicle lotion (n=241) tazarotene 0.045% lotion (n=238) ** *** -31.0% -40.8% -48.5%-35.3% -50.4% -59.4% -70% -60% -50% -40% -30% -20% -10% 0% baseline week 4 week 8 week 12 vehicle lotion (n=71) tazarotene 0.045% lotion (n=72) -21.5% -29.8% -39.9%-32.5% -46.6% -55.4% -70% -60% -50% -40% -30% -20% -10% 0% baseline week 4 week 8 week 12 vehicle lotion (n=199) tazarotene 0.045% lotion (n=192) *** *** *** *** 20–29 years13–19 years 30+ years ls m e an c h an g e f ro m b as e lin e ls m e an c h an g e f ro m b as e lin e a. in�ammatory lesions b. nonin�ammatory lesions *p<0.05; **p<0.01; ***p≤0.001 vs vehicle. no significant differences between age groups at weeks 4, 8, or 12. itt, intent to treat; ls, least-squares. efficacy and safety of tazarotene 0.045% lotion in female patients with moderate-to-severe acne: post hoc analysis by age figure 3. cutaneous safety and tolerability by age group (pooled safety population) p e rc e n ta g e o f p ar ti ci p an ts 0% 20% 40% 60% 80% 100% 13–19 years 30+ years taz veh taz veh taz veh 0% 20% 40% 60% 80% 100% 13–19 years 30+ years taz veh taz veh taz veh p e rc e n ta g e o f p ar ti ci p an ts 0% 20% 40% 60% 80% 100% 13–19 years 30+ years taz veh taz veh taz veh 0% 20% 40% 60% 80% 100% 13–19 years 30+ years taz veh taz veh taz veh scaling 20–29 years erythema 20–29 years hyperpigmentation 20–29 years itching 20–29 years baseline week 12 moderate severe mild moderate severe mild data for ‘none’ are not shown. n values were as follows: 13–19 years: taz baseline n=190, taz week 12 n=166, veh baseline n=197, veh week 12 n=184; 20–29 years: taz baseline n=228, taz week 12 n=198, veh baseline n=231, veh week 12 n=198; 30+ years: taz baseline n=70, taz week 12 n=59, veh baseline n=67, veh week 12 n=62. taz, tazarotene 0.045% lotion; veh, vehicle lotion. results participants � the pooled population included 1,013 adolescent and adult female participants: 13–19 years (tazarotene n=192, vehicle n=199); 20–29 years (n=238, n=241); 30+ years (n=72, n=71) � >90% of female participants in each age group had an egss score of 3 (‘moderate’) at baseline: 13–19 years (91.6%), 20–29 years (93.1%), 30+ years (93.0%) efficacy � female participants in all 3 age groups had approximately 55–60% mean reductions from baseline in inflammatory and noninflammatory lesion counts with tazarotene 0.045% lotion (figure 1) • in the younger groups (13–19 and 20–29 years), least-squares mean percent reductions in lesion counts were significantly greater with tazarotene versus vehicle at week 12 • similar reductions with tazarotene were observed in older participants (30+ years); however, the results were not statistically significant versus vehicle, possibly due to the smaller sample size and/or relatively larger vehicle response • in tazarotene-treated females, no significant differences were observed across age groups at any week � at week 12, more females achieved treatment success with tazarotene versus vehicle: 13–19 years (26.4% vs 14.8%, p<0.01); 20–29 years (38.4% vs 25.5%, p<0.01); 30+ years (36.4% vs 25.7%, p>0.05); there was a significant difference across the 3 age groups (p<0.05) � images depicting acne improvement are shown in figure 2 safety � no notable age-related patterns were found for safety outcomes � most treatment-related teaes with tazarotene were mild or moderate; application site pain and dryness were the most common treatment-related teaes (table 1) � less than 10% of tazarotene-treated participants in any age group had hypopigmentation, burning, or stinging at baseline or week 12 (data not shown) � across all age groups, rates of erythema and hyperpigmentation—more common at baseline than scaling or itching—remained relatively unchanged or reduced from baseline to week 12 (figure 3) figure 2. acne improvements in females treated with tazarotene 0.045% lotion protocol: v01-123a-302 | site: 229 | subject: 229006 | initials: otd visit: baseline day 0 | visit date: 21sep2017 | view: right | treatment: idp-123 lotion protocol: v01-123a-302 | site: 210 | subject: 210004 | initials: kps visit: baseline day 0 | visit date: 04dec2017 | view: right | treatment: idp-123 lotion protocol: v01-123a-302 | site: 234 | subject: 234029 | initials: sec visit: baseline day 0 | visit date: 05feb2018 | view: right | treatment: idp-123 lotion protocol: v01-123a-302 | site: 229 | subject: 229006 | initials: otd visit: week 12 | visit date: 13dec2017 | view: right | treatment: idp-123 lotion protocol: v01-123a-302 | site: 210 | subject: 210004 | initials: kps visit: week 12 | visit date: 27feb2018 | view: right | treatment: idp-123 lotion protocol: v01-123a-302 | site: 234 | subject: 234029 | initials: sec visit: week 12 | visit date: 01may2018 | view: right | treatment: idp-123 lotion 18-year-old female 24-year-old female 32-year-old female baseline egss=3 baseline egss=3 baseline egss=3 week 12 egss=1 week 12 egss=0 week 12 egss=1 individual results may vary. egss, evaluator’s global severity score (0=clear, 1=almost clear, 2=mild, 3=moderate, 4=severe). linda stein gold, md1; hilary baldwin, md2; fran e cook-bolden, md3; lawrence green, md4; glynis ablon, md5; neil sadick, md6; jonathan weiss, md7; eric guenin, pharmd, phd, mph8 1henry ford hospital, detroit, mi; 2the acne treatment and research center, brooklyn, ny and the robert wood johnson university hospital, new brunswick, nj; 3fran e. cook-bolden, md, pllc and department of dermatology, mount sinai hospital center, new york, ny; 4department of dermatology, george washington university school of medicine, washington, dc; 5ablon skin institute & research center, manhattan beach, ca; 6department of dermatology, weill cornell medical college, new york, ny and sadick dermatology, new york, ny; 7georgia dermatology partners and gwinnett clinical research center, inc., snellville, ga; 8ortho dermatologics*, bridgewater, nj *ortho dermatologics is a division of bausch health us, llc. table 1. treatment-emergent adverse events by age group (pooled safety population) percentage of participants 13–19 years 20–29 years 30+ years taz (n=190) veh (n=197) taz (n=228) veh (n=231) taz (n=70) veh (n=67) any teae 28.4 19.8 35.5 18.2 25.7 16.4 treatment-related teaes 14.7 1.0 16.2 2.2 12.9 1.5 intensity of treatment-related teaes mild 8.4 0.5 10.5 0.9 10.0 0 moderate 5.3 0.5 4.4 0.9 2.9 1.5 severe 1.1 0 1.3 0.4 0 0 common treatment-related teaesa application site pain 6.8 0.5 6.6 0.4 7.1 0 application site dryness 4.2 0 6.6 0.4 2.9 0 application site erythema 4.2 0 1.8 0 0 0 application site exfoliation 2.6 0 3.9 0 1.4 0 application site pruritus 2.6 0 0.4 0 1.4 0 areported in ≥2% of tazarotene-treated participants in any age group. taz, tazarotene 0.045% lotion; teae, treatment-emergent adverse event; veh, vehicle lotion. conclusions � treatment with tazarotene 0.045% lotion reduced inflammatory and noninflammatory lesions by approximately 55–60% in adolescent and adult females with moderate-tosevere acne � no age-related trends for safety/tolerability were observed; erythema and hyperpigmentation remained relatively unchanged or improved with tazarotene 0.045% lotion references 1. zaenglein al, et al. j am acad dermatol. 2016;74(5):945-973.e933. 2. skroza n, et al. j clin aesthet dermatol. 2018;11(1):21-25. 3. collier cn, et al. j am acad dermatol. 2008;58(1):56-59. 4. tan jk, et al. j cutan med surg. 2008;12(5):235-242. 5. tanghetti ea et al. j drugs dermatol. 2020;19(3):272-279. author disclosures linda stein gold has served as investigator/consultant or speaker for ortho dermatologics, leo pharma, dermavant, incyte, novartis, abbvie, pfizer, sun pharma, ucb, arcutis and lilly. hilary baldwin has served as advisor, investigator, and on speakers’ bureaus for almiral, cassiopea, foamix, galderma, ortho dermatologics, sol gel, and sun pharma. fran cook-bolden has served as consultant, speaker, investigator for galderma, leo pharma, almirall, cassiopea, ortho dermatologics, investigators encore, foamix, hovione, aclaris, cutanea. lawrence green as served as investigator, consultant, or speaker for: almirall, cassiopea, galderma, ortho dermatologics, sol gel, sun pharma, and vyne. glynis ablon has served as a consultant and advisory board member for galderma, sinclair, thermi-almirall, erchonia, sunetics, nutrafol, and lifes2good. neil sadick has served on advisory boards, as a consultant, investigator, speaker, and/or other and has received honoraria and/or grants/research funding from almirall, actavis, allergan, anacor pharmaceuticals, auxilium pharmaceuticals, bausch health, bayer, biorasi, btg, carma laboratories, cassiopea, celgene, cutera, cynosure, dusa pharmaceuticals, eclipse medical, eli lilly and company, endo international, endymed medical, ferndale laboratories, galderma, gerson lehrman group, hydropeptide, merz aesthetics, neostrata, novartis, nutraceutical wellness, palomar medical technologies, prescriber’s choice, regeneron, roche laboratories, samumed, solta medical, storz medical ag, suneva medical, vanda pharmaceuticals, and venus concept. jonathan weiss is a consultant, speaker, advisor, and/or researcher for abbvie, ortho dermatologics, jansen biotech, dermira, almirall, brickell biotech, dermtech, scynexis. eric guenin is an employee of ortho dermatologics and may hold stock and/or stock options in its parent company. skin january 2018 volume 2 issue 1 copyright 2018 the national society for cutaneous medicine 80 brief articles linear psoriasis: a case report of a 71-year-old female chun-hui yi md phd a , chen chen md b , allen n sapadin md jd c , robert g phelps md b a department of pathology, mount sinai health system, st. luke’s-roosevelt hospital and beth israel medical center, new york, ny b department of pathology, mount sinai school of medicine, new york, ny c allen sapadin dermatology and dermatologic surgery, hackensack, nj a 71-year-old woman presented to the clinic with a one-month history of pruritic, burning, flaky pink to dark red erythematous plaques. the lesions had a very narrow, linear, blashkoid distribution which extended from the left lateral sole to the popliteal region (figure 1). the right leg also had a similar erythematous plaque located at the pretibial region. the patient had no other lesions or previous history of psoriasis. punch biopsies were performed which revealed orthokeratosis and mounds of parakeratosis, and traumatized koebnerization. elongation of rete ridges was not prominent, however, mild psoriasiform hyperplasia and suprapapillary thinning of the epidermis with mildly increased vessels in the dermal papillae and a lymphocytic infiltrate in the upper dermis were observed. (figure 2a-d). the findings were consistent with features of an early psoriasis lesion. pas and the direct immunofluorescence (dif) stains were negative, but ki-67 showed increased expression (figure 2e). together with the clinical presentation, a diagnosis of linear psoriasis was favored. abstract a 71-year-old woman presented with a one-month history of pruritus, burning, flaky, and erythematous plaques. the lesions had a very narrow lineal distribution, extending from the lateral left sole to the left popliteal region. microscopically, the skin biopsy sample revealed orthokeratosis, parakeratosis and traumatized koebnerization. elongation of rete ridges was not prominent. the patient had a good clinical response to oral prednisone. linear psoriasis is a rare variant of psoriasis of unknown etiology. approximately 23 reports have been published in the english literature. the main differential diagnosis is inflammatory linear verrucous epidermal nevus (ilven). thorough clinicopathologic findings and response to treatment are all required in the diagnosis and management of this rare form of psoriasis. case report skin january 2018 volume 2 issue 1 copyright 2018 the national society for cutaneous medicine 81 figure 1. the patient presented with a one-month history of pruritic, burning, flaky pink to dark red erythematous plaques. the lesions had a very narrow, linear, blashkoid distribution extending from the left lateral sole to the popliteal region. figure 2. histologic features of the pruritic erythematous plaque. biopsy of thee plaque showed mounds of parakeratosis in the stratum corneum, retention of the granular layer, mildly increased vessels in the dermal paplillae, and lymphocytic infiltrates in the upper dermis (a-c). focal munro pustules were also present (d). ki-67 was found to be increased (e). skin january 2018 volume 2 issue 1 copyright 2018 the national society for cutaneous medicine 82 linear psoriasis is a rare variant of psoriasis. approximately 23 reports have been published in the english literature. it is characterized by a linear distribution of the psoriatic lesions along blaschko’s lines. 1 it typically occurs in the lower extremities of older individuals, although rare occurrences in children also have been reported. the etiology of linear psoriasis is not known. happle suggested that it may be the result of somatic recombination of genes that predisposes the patients to segmental mosaicism. 2 there may also be an association between human leukocyte antigen class i alleles and development of the disease. 3 linear psoriasis typically responds well to local treatment. the main differential diagnosis of this entity is inflammatory linear verrucous epidermal nevus (ilven), psoriasis superimposed upon an epidermal nevus in a linear growth pattern or other linear dermatosis. 4 ilven may have a similar clinical presentation to linear psoriasis as highly pruritic psoriasiform skin lesions that tend to occur in the left lower extremity. however, ilven usually occurs in early childhood with a female predominance whereas linear psoriasis frequently occurs in the elderly. the rash of linear psoriasis usually has mild pruritus or no symptoms. 5, 6 it is interesting to note that several reported cases of linear psoriasis in the literature also revealed a tendency to involve the left side of the body. 3, 7 previously reported cases of linear psoriasis showed wide, band-like linear lesions, however, the rash on this patient showed a very narrow linear distribution similar to ilven or epidermal nevus. child (congenital hemidysplasia with ichthyosiform erythroderma and limb defects) syndrome also presents with unilateral linear skin rashes, characterized by erythroderma and ichthyosis with an equal leftor right-sided predominance. it is an x-linked dominant hereditary disease that only occurs in girls, since the mutation is lethal to male embryos, and it is treated with topical cholesterol and simvastatin. 8, 9 patients afflicted with this disorder also have hemidysplasia and developmental defects in other organ systems. unlike child syndrome, linear psoriasis and ilven are not hereditary and present later in life. distinguishing between ilven and linear psoriasis is difficult in some cases since the conditions have overlapping clinical and histological features. recently, a few immunohistochemistry markers have been shown to be helpful in this diagnosis, such as ki-67, keratin 10, and involucrin. ki-67 index is usually high in linear psoriasis but remains low in ilven. 10 keratin 10 is rarely expressed in psoriasis, but the level is normal in ilven. 1 involucrin is a transglutaminase substrate protein present in keratinocytes of epidermis. it is crosslinked to other membrane proteins and contributes to the formation of the cornified cell envelope. 5 while it is present in the upper portion of the spinous and granular layer of the normal epidermis, it is expressed in the subbasal layer in psoriasis. in ilven, transglutaminase expression is increased in areas of the orthokeratosis but decreased in areas of parakeratosis . 5 furthermore, ilven is refractory to antipsoriatic treatment, whereas linear psoriasis responds well to topical discussion skin january 2018 volume 2 issue 1 copyright 2018 the national society for cutaneous medicine 83 antipsoriatic agents or narrow-band uvb phototherapy. 11 in summary, we report a rare case of unilateral linear psoriasis involving the lower leg of a 71-year-old female, and discuss the clinical, histological features of the lesion, and the most common differential diagnosis. unilateral linear psoriasis is rarely reported and often misdiagnosed as ilven. conflict of interest disclosures: none. funding: none. corresponding author: chun-hui yi, md, phd department of pathology mount sinai health system st. luke’s-roosevelt hospital and beth israel medical centers 1000 tenth avenue new york, ny 10019 212-523-8631 (office) 212-523-7232 (fax) chunhui.yi@mountsinai.org references: 1. figueiras dde a, cauas rc, takano dm, ramos tb, marinho ak, bezerra ms. linear psoriasis: case report on three year old child. an bras dermatol. 2015;90(3 suppl 1):194-196. 2. happle r. somatic recombination may explain linear psoriasis. j med genet. 1991;28(5):337. 3. li w, man xy. linear psoriasis. cmaj. 2012;184(7):789. 4. happle r. superimposed linear psoriasis: a historical case revisited. j dtsch dermatol ges. 2011;9(12):10271028. 5. ferreira fr, di chiacchio ng, alvarenga ml, mandelbaum sh. involucrin in the differential diagnosis between linear psoriasis and inflammatory linear verrucous epidermal nevus: a report of one case. an bras dermatol. 2013;88(4):604607. 6. akelma az, cizmeci mn, kanburoglu mk, mete e. a diagnostic dilemma: inflammatory linear verrucous epidermal nevus versus linear psoriasis. j pediatr. 2013;162(4):879879. 7. singh n, noorunnisa n. linear psoriasis: a rare presentation. indian dermatol online j. 2012;3(1):71-73. 8. mi xb, luo mx, guo ll, zhang td, qiu xw. child syndrome: case report of a chinese patient and literature review of the nad[p]h steroid dehydrogenase-like protein gene mutation. pediatr dermatol. 2015;32(6):e277-282. 9. noguera-morel l, hernandez-ostiz s, casas-fernandez l, et al. child syndrome with minimal limb abnormalities. j eur acad dermatol venereol. 2015. 10. yin b fau ran y-p, ran yp fau wang p, wang p fau lama j, lama j. is it inflammatory linear verrucous epidermal nevus or linear psoriasis? chinese medical journal. 2013;126(0366-6999 (print)):17941795. skin january 2018 volume 2 issue 1 copyright 2018 the national society for cutaneous medicine 84 11. brinca a, santiago f, serra d, andrade p, vieira r, figueiredo a. linear psoriasis a case report. case rep dermatol. 2011;3(1):8-12. skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 524 research letter brodalumab in the treatment of moderate-to-severe psoriasis in patients refractory to anti-interleukin-17a therapies: evaluation of secondary endpoints grace kimmel, md1, margot chima, md1, hee jin kim, md1, jennifer bares, md1, alex yaroshinsky, phd2, giselle singer, bs1, soo jung kim, md3, jerry bagel, md4, mark lebwohl, md1 1 department of dermatology, icahn school of medicine at mount sinai, new york, ny 2 ziropa, inc, sunnyvale, ca 3 department of dermatology, baylor college of medicine, houston, tx 4 psoriasis treatment center of central new jersey, east windsor, nj brodalumab is an interleukin-17 receptor a antagonist approved for the treatment of moderate-to-severe plaque psoriasis. in our previous publication, we reported that the majority of patients who had previously failed treatment with an anti-il-17a agent had significant improvement with brodalumab. as-observed (ao) results showed psoriasis area and severity index (pasi)-75, pasi-90, and pasi-100 scores in 76%, 50%, and 32% of patients, respectively, at week 16. using a nonresponder imputation (nri), pasi-75, pasi90, and pasi-100 scores were seen in 67%, 44%, and 28% of patients1. abstract background: brodalumab is an interleukin-17 receptor a antagonist approved for the treatment of moderate-to-severe plaque psoriasis. our prior publication reported significant disease improvement with brodalumab in psoriasis patients who had previously failed treatment with an anti-il-17a agent. methods: we conducted an institutional review board (irb)-approved open-label study of a total of 39 subjects enrolled at 3 sites with moderate-to-severe psoriasis. all patients previously failed treatment with an il-17a agent. subjects received brodalumab 210 mg via subcutaneous injection at weeks 0, 1, and 2, followed by 210 mg every 2 weeks, up to week 16. subjects were evaluated monthly for improvement in pasi and spga. results: of the baseline comorbidities assessed, the only statistically significant difference between responders and non-responders was the presence of higher weight/bmi in non-responders in the ao dataset; this trend disappeared in the nri dataset. of the patients that dropped out of the trial early, 3 of the 5 had pasi improvements of >60%. a rapid onset to disease improvement was seen in the trial. conclusion: these results indicate that brodalumab may be a good treatment choice for psoriasis patients, including those with severe disease and/or underlying comorbidities. skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 525 although the majority of these patients improved on brodalumab treatment, we sought to investigate factors that differed between the patients who had treatment success with brodalumab and those who did not, as well as other secondary endpoints. an institutional review board (irb)approved open-label study was conducted on a total of 39 subjects enrolled at 3 sites with moderate-to-severe psoriasis. all investigators were risk evaluation and mitigation (rems) certified. subjects received brodalumab 210 mg via subcutaneous injection of prefilled syringes at weeks 0, 1, and 2, followed by 210 mg every 2 weeks, up to week 16. all patients previously failed treatment with an il-17a agent, defined as treatment with either secukinumab or ixekizumab for > 3 months without achieving pasi-75 response, or a 50% loss of original improvement. endpoints of this extension study included evaluation of baseline characteristics and comorbidities of responders vs nonresponders, including weight, body mass index (bmi), smoking status, baseline pasi and static physician’s global assessment (spga) scores, and body sites involved. other endpoints included the extent of improvement in non-responders, characterization of the patients who discontinued early from the trial, time to improvement in pasi scores, and the proportion of patients achieving a >2-point reduction in spga at week 16. for the purposes of these endpoints, “responders” were defined as patients who met spga 0 or 1 (clear or almost clear) or pasi-75 at week 16. of the baseline characteristics (tables 1, 2), the only statistically significant difference between responders and non-responders was the presence of higher weight/bmi in non-responders, seen in the ao dataset. this trend disappears in the nri dataset. this is consistent with the known efficacy of brodalumab for obese patientsin its phase iii trials, the efficacy of brodalumab did not differ between nonobese vs obese patients (bmi >30 kg/m2)2. there was also a nonstatistically significant trend toward more severe disease in the non-responders. a total of 5 patients discontinued participation in the trial. the most common reason for early discontinuation was lack of efficacy. percent improvement in pasi scores at early termination were 81% (week 4), and 60%, 35%, 4%, and 61% (week 12). the bmi of the patients who discontinued participation ranged from 20.9 to 29.8. for those patients who were nonresponders at week 16, we observed a partial response (pasi-50) in 50% (ao)/30.8% (nri). a rapid onset of disease improvement was observed. by week 4, 53.8% and 23.1% of patients achieved pasi-50 and pasi-75, respectively; increasing to 88.2% and 76.5% at week 16 (ao). a >2-grade improvement in spga at week 16 was achieved by 61.5% of patients (both ao, nri). in conclusion, the only statistically significant difference between responders and nonresponders was the presence of higher weight/bmi in the ao dataset; this effect disappeared in the nri dataset. these data suggest that brodalumab may be a good treatment option for psoriasis patients who have failed other biologics, including the anti-il-17a class, regardless of their underlying disease severity or comorbidities. skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 526 abbreviations: ao: as-observed pasi: psoriasis area and severity index nri: non-responder imputation irb: institutional review board rems: risk evaluation and mitigation strategy spga: static physician’s global assessment conflict of interest disclosures: grace kimmel, md: advisory board member: bristol myers squibb (may 2020); pfizer (jan 2021) margot chima, md: none. hee jin kim, md: none. jennifer bares, md: none. alex yaroshinsky, phd: consultant, owns equity: ziropa. consultant: dermoforce, mesoblast, maplight, amo, neuren, novo ventures. giselle singer, bs: none. soo jung kim, md: none jerry bagel, md: dr. bagel has received research funds payable to the psoriasis treatment center of new jersey from abbvie, amgen, arcutis biotherapeutics, boehringer ingelheim, bristol myers squibb, celgene corporation, corrona llc, dermavant sciences, ltd, dermira/ucb, eli lilly and company, glenmark pharmaceuticals ltd, janssen biotech, kadmon corporation,leo pharma lycera corp, menlo therapeutics, novartis, pfizer, regeneron pharmaceuticals, sun pharma, taro pharmaceutical industries ltd, and valeant pharmaceuticals; consultant fees from abbvie, amgen, celgene corporation, eli lilly and company, janssen biotech, novartis, sun pharmaceutical industries ltd, and valeant pharmaceuticals; and fees for speaking from abbvie, celgene corporation, eli lilly, janssen biotech, and novartis. . mark lebwohl, md: mark lebwohl is an employee of mount sinai and receives research funds from: abbvie, amgen, arcutis, avotres, boehringer ingelheim, dermavant sciences, eli lilly, incyte, janssen research & development, llc, ortho dermatologics, regeneron, and ucb, inc. dr. lebwohl is also a consultant for aditum bio, almirall, altrubio inc., anaptysbio, arcutis, inc., aristea therapeutics, arrive technologies, avotres therapeutics, biomx, boehringer-ingelheim, bristolmyers squibb, cara therapeutics, castle biosciences, corrona, dermavant sciences, dr. reddy’s laboratories, evelo biosciences, evommune, inc., facilitatation of international dermatology education, forte biosciences, foundation for research and education in dermatology, helsinn therapeutics, hexima ltd., leo pharma, meiji seika pharma, mindera, pfizer, seanergy, and verrica. funding: this study received funding from ortho dermatologics. corresponding author: grace kimmel, md department of dermatology icahn school of medicine at mount sinai 1425 madison ave box 1047, l2-17 new york, ny 10029 email: gracewkimmel@gmail.com references: 1. kimmel, g., et al., brodalumab in the treatment of moderate to severe psoriasis in patients when previous anti-interleukin 17a therapies have failed. j am acad dermatol, 2019. 81(3): p. 857859. 2. hsu, s., et al., comparable efficacy and safety of brodalumab in obese and nonobese patients with psoriasis: analysis of two randomized controlled trials. br j dermatol, 2020. 182(4): p. 880-888. mailto:gracewkimmel@gmail.com skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 527 table 1 baseline characteristics of responders and non-responders, ao dataset baseline characteristics week 16 responder (n=26) week 16 non responder (n=8) week 16 missing (n=5) age (years) n 26 8 5 mean (se) 53.2 (3.43) 49.9 (3.98) 38.2 (6.71) median 51.50 50.00 34.00 min, max 19, 91 28, 66 24, 56 p-value [a] 0.6149 weight (lb) n 26 8 5 mean (se) 191.3 (7.46) 252.1 (31.56) 160.8 (14.61) median 188.0 241.00 158.00 min, max 122, 267 155, 425 118, 208 p-value [a] 0.0085 bmi (kg/m2) n 26 8 5 mean (se) 28.6 (0.90) 37.4 (3.95) 25.0 (1.50) median 28.55 35.45 25.00 min, max 21, 39 25, 59 21, 30 p-value [a] 0.0023 smoking status, n(%) no 17 (65.4%) 5 (62.5%) 4 (80.0%) yescurrent 2 (7.7%) 2 (25.0%) 0 yesformer 7 (26.9%) 1 (12.5%) 1 (20.0%) p-value [b] 1.0000 pasi at baseline n 26 8 5 mean (se) 21.2 (2.61) 19.3 (5.75) 17.6 (7.42) median 18.15 12.20 10.50 min, max 5, 51 7, 55 4, 43 p-value [a] 0.7447 spga at baseline, n(%) 3 17 (65.4%) 3 (37.5%) 3 (60.0%) 4 9 (34.6%) 5 (62.5%) 2 (40.0%) p-value [b] 0.2278 comorbidities, n(%) diabetes mellitus 6 (23.1%) 3 (37.5%) 0 p-value [b] 0.6488 hypertension 13 (50.0%) 3 (37.5%) 2 (40.0%) p-value [b] 0.6933 hyperlipidemia 9 (34.6%) 3 (37.5%) 0 p-value [b] 1.0000 psoriatic arthritis 2 (7.7%) 0 3 (60.0%) p-value [b] 1.0000 history of depression 5 (19.2%) 0 0 p-value [b] 0.3086 locations, n(%) head 17 (65.4%) 6 (75.0%) 3 (60.0%) p-value [b] 1.0000 trunk 21 (80.8%) 6 (75.0%) 4 (80.0%) p-value [b] 1.0000 upper extremities 22 (84.6%) 8 (100.0%) 3 (60.0%) p-value [b] 0.5515 lower extremities 25 (96.2%) 8 (100.0%) 4 (80.0%) p-value [b] 1.0000 [a] p-value is from a t-test comparing week 16 responder with week 16 non-responder; [b] p-value is from the fisher's exact test comparing week 16 responder with week 16 non-responder. skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 528 table 2 baseline characteristics of responders and non-responders, nri dataset baseline characteristics week 16 responder (n=26) week 16 nonresponder (n=13) age (years) n 26 13 mean (se) 53.2 (3.43) 45.4 (3.76) median 51.50 47.00 min, max 19, 91 24, 66 p-value [a] 0.1655 weight (lb) n 26 13 mean (se) 191.3 (7.46) 217.0 (23.44) median 188.00 194.00 min, max 122, 267 118, 425 p-value [a] 0.1963 bmi (kg/m2) n 26 13 mean (se) 28.6 (0.90) 32.7 (2.99) median 28.55 29.80 min, max 21, 39 21, 59 p-value [a] 0.1019 smoking status, n(%) no 17 (65.4%) 9 (69.2%) yescurrent 2 (7.7%) 2 (15.4%) yesformer 7 (26.9%) 2 (15.4%) p-value [b] 1.0000 pasi at baseline n 26 13 mean (se) 21.2 (2.61) 18.7 (4.36) median 18.15 12.00 min, max 5, 51 4, 55 p-value [a] 0.6016 spga at baseline, n(%) 3 17 (65.4%) 6 (46.2%) 4 9 (34.6%) 7 (53.8%) p-value [c] 0.2497 comorbidities, n(%) diabetes mellitus 6 (23.1%) 3 (23.1%) p-value [b] 1.0000 hypertension 13 (50.0%) 5 (38.5%) p-value [b] 0.7342 hyperlipidemia 9 (34.6%) 3 (23.1%) p-value [b] 0.7144 psoriatic arthritis 2 (7.7%) 3 (23.1%) p-value [b] 0.3102 history of depression 5 (19.2%) 0 p-value [b] 0.1488 locations, n(%) head 17 (65.4%) 9 (69.2%) p-value [b] 1.0000 trunk 21 (80.8%) 10 (76.9%) p-value [b] 1.0000 upper extremities 22 (84.6%) 11 (84.6%) p-value [b] 1.0000 lower extremities 25 (96.2%) 12 (92.3%) p-value [b] 1.0000 [a] p-value is from a t-test comparing week 16 responder with week 16 non-responder; [b] p-value is from the fisher's exact test comparing week 16 responder with week 16 non-responder; [c] p-value is from the chisquare test comparing week 16 responder with week 16 non-responder skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 529 skin december 2018 volume 2 supplemental issue copyright 2018 the national society for cutaneous medicine 99 rising derm stars prophylactic botulinum toxin in post-excisional scars: a randomized, doubleblinded, controlled clinical trial danielle p dubin ba, richard l torbeck md, daniel m bernstein md, matthew j lin md, hooman khorasani md background: excision of non-melanoma skin cancer on the face is usually curative, but the resultant scar in this cosmetically sensitive area may cause significant distress. excessive wound tension may impair the healing process and lead to unsightly scars1; therefore, one of the key principles in cutaneous surgery is to minimize wound tension. botulinum toxin is utilized as a treatment for facial rhytids due to its ability to induce a chemical paralysis of the musculature2. it has been hypothesized that it may also be used to minimize facial scars by paralyzing facial muscles, thereby leading to reduced wound tension. objective: to assess post-operative scar outcomes after administration of botulinum toxin at the time of excisional skin cancer surgery. methods: in this single center, single surgeon, double-blinded, prospective, randomized clinical trial, 25 caucasian patients ≥ 18 years of age were randomized to receive either botulinum toxin injections or placebo injections of normal saline immediately following closure of skin cancer defects from mohs micrographic surgery on the forehead. all defects underwent layered closure by a single dermatologic surgeon with thirteen years of surgical experience. botulinum toxin (50 units) or saline (1 ml) were then injected in a standardized pattern on the forehead (figure 1). wounds were dressed in a standardized manner with mastitol®, steri-strips®, telfa®, gauze, hypafix® and cutaneous sutures were removed 7 days after surgery. the primary outcome was a blinded assessment of the scar six months after surgery with the modified manchester scar scale (mmss) and visual analog scale (vas). the study arms were compared using the mannwhitney u test. two-tailed tests with a significance level of 5% were used. results: the placebo and botulinum toxin groups were similar in terms of age (mean of 57 and 59), gender (female:male ratio 5:6 and 5:9), smoking history (2 and 3 patients, respectively), autoimmune disorders (1 each), and scar location. there was no significant difference in mmss scores between the study arms (median 10.00 and 10.15, p = 0.79). similarly, there was no significant difference in the vas scores (median values 3 and 3, p = 0.87). analysis of subgroups stratified by age, gender, closure type, scar orientation, and sublocations also failed to demonstrate a significant difference. conclusion: when administered at the time of wound closure, botulinum toxin does not significantly improve post-operative facial scar outcomes. further studies are needed to determine the efficacy of prophylactic skin december 2018 volume 2 supplemental issue copyright 2018 the national society for cutaneous medicine 100 administration of botulinum toxin prior to wound closure, which may allow for maximum chemical paralysis of the facial musculature. figure 1: standardized injection pattern for both study arms. figure 2: box plot comparing vas and mmss for the placebo versus botulinum toxin study arms. references: references: 1. meyer, m, and da mcgrouther. “a study relating wound tension to scar morphology in the pre-sternal scar using langers technique.” british journal of plastic surgery, vol. 44, no. 4, may 1991, pp. 291–294., doi:10.1016/0007 1226(91)90074-t. 2. carruthers, jean d.a., and j. alastair carruthers. “treatment of glabellar frown lines with c. botulinum-a exotoxin.” the journal of dermatologic surgery and oncology, vol. 18, no. 1, 1992, pp. 17–21., doi:10.1111/j.1524 4725.1992.tb03295.x skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 8 in-depth review association between pseudoxanthoma elasticum and bleeding lily lebwohl1, robert phelps, md1 1icahn school of medicine at mount sinai, new york, ny pseudoxanthoma elasticum (pxe) is a rare genetic disease caused by a mutation of the abcc6 gene. this results in calcification of elastic fibers of the skin, eye and other organs and tissues that contain elastin. the internal elastic lamina of arteries can be affected, resulting in vascular complications including bleeding. ringpfeil et. al. described mutations in the abcc6 transporter protein inherited in a an autosomal recessive pattern in pxe.1 consequently, any organ containing elastic tissue can be affected, with skin2 and eyes 3 being the most common. skin lesions are characterized by yellow xanthoma-like patches, papules and folds (figure 1a,1b). mucosal lesions have also been described, particularly on the oral mucosa (figure 2). and the classic eye characteristics are angioid streaks in the retina (figure 3) 4 though any elasticcontaining tissue can be affected. heart valves can be involved, resulting in mitral valve prolapse5 and myocardial infarctions at an early age6. the latter complication occurs as a consequence of calcification of the coronary arteries. pxe can be identified at any age and has been reported in ages as young as age 4. 7 it is associated with numerous complications including characteristic skin lesions (figure 1a, 1b) and angioid streaks in the retina (figure 3). serious vascular complications including myocardial infarction and stroke at a young age have been reported 8. because calcified arteries can bleed, hemorrhage from various organs is a reported complication of pxe. we therefore conducted a literature review of all english language published articles reporting bleeding in patients with pxe. abstract pseudoxanthoma elasticum (pxe) is a rare genetic disease caused by a mutation of the abcc6 gene, resulting in calcification of elastic fibers of the skin, eye and other organs and tissues that contain elastin. because calcified arteries can bleed, hemorrhage from various organs is a reported complication of pxe. we conducted a literature review of all english language published articles reporting bleeding in patients with pxe. in this literature review, we identified 51 papers. of those, 30 (59%) included at least 1 case of bleeding. within these 30 papers, bleeding was reported in a total of 130 patients. of the cases of bleeding, 113 occurred in the gastrointestinal tract, 12 occurred in the brain, 2 in the skin, 1 in the nose, 1 in the gums and 1 in the uterus. clinicians and patients should be made aware of the risk of these significant complications, to facilitate preventive measures, prompt recognition and treatment. introduction https://sciwheel.com/work/citation?ids=11323469&pre=&suf=&sa=0&dbf=0 https://sciwheel.com/work/citation?ids=11604932&pre=&suf=&sa=0&dbf=0 https://sciwheel.com/work/citation?ids=11582277&pre=&suf=&sa=0&dbf=0 https://sciwheel.com/work/citation?ids=11582288&pre=&suf=&sa=0&dbf=0 skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 9 figure 1. a) yellow xanthoma-like papules typical of pxe b) papules become confluent to form redundant folds in the axilla. a pubmed search was conducted using these terms: bleed, hemorrhage, haemorrhage, and pseudoxanthoma elasticum. review articles were not included, nor were articles that did not include original cases of bleeding or hemorrhage. for reasons of scope, we did not include retinal bleeding in this review. for each report, we recorded the year of publication, number of subjects with pxe, the number with a bleeding event, the site of bleeding, and other complications among those with bleeding. figure 2. yellow papules and patches on the lower lip. using the search terms outlined above, we identified 51 papers. of those, 30 (59%) included at least 1 case of bleeding. 9-38 (the 21 remaining papers were excluded because they were review articles or did not include cases.) within these 30 papers, bleeding was reported in a total of 130 patients. of the cases of bleeding, 113 occurred in the gastrointestinal tract, 12 occurred in the brain, 2 in the skin, 1 in the nose, 1 in the gums and 1 in the uterus (see table 1). figure 3. angioid streaks of the retina methods results a . b https://sciwheel.com/work/citation?ids=11604906&pre=&suf=&sa=0&dbf=0 skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 10 figure 4 shows calcified elastic fibers in the skin biopsy of a patient with pxe. retinal bleeding is very common, but bleeding at other sites can also occur and is the subject of this review. there were many sites of bleeding identified in this literature review, including the brain 9, skin 35, nose35, uterus 35 and gums, 13 but gastrointestinal bleeding was particularly common 11,15,28,30, followed by cerebral hemorrhage 12,14. because of the bleeding tendency, certain management table 1 year author site of bleeding other complications number in study number with bleeding 2020 sunmonu na brain stroke 1 1 2021 lanfranconi s brain stroke 1 1 2016 dibi a gastrointestinal vascular disease 2 2 2014 drue hc brain 1 1 2008 adam am gums 1 1 2008 bock a brain 1 1 2007 goral v gastrointestinal 1 1 2006 antiga e gastrointestinal 1 1 2005 golliet-mercier n gastrointestinal 1 1 2004 makharia gk gastrointestinal 1 1 2002 ospedale s gastrointestinal/intercranial gastric artery aneurysm/ischaemic attack 29 2 1996 spinzi g gastrointestinal 2 2 2000 costopanagiotou e gastrointestinal 1 1 1992 yap ey gastrointestinal aneurysms of the gastric arteries 1 1 1991 yamamura h gastrointestinal 1 1 1990 slade ak gastrointestinal 1 1 1988 jacyk wk gastrointestinal 7 1 1988 kundrotas l gastrointestinal 1 1 1988 belli a gastrointestinal vascular abnormalities 2 2 1982 drost h gastrointestinal 1 1 1982 morgan aa gastrointestinal 1 1 1980 keim hj gastrointestinal total gastrectomy and partial jejunal resection 1 1 1973 olbromska w gastrointestinal 1 1 1973 van waes l gastrointestinal 1 1 1968 gignoux r gastrointestinal total gastrectomy 1 1 1966 dhers a gastrointestinal 3 3 2000 van den berg js gastrointestinal, skin, nose, uterus 100 17 gastrointestinal; 2 skin; 1 nose; 1 uterus 1967 grant ak gastrointestinal 3 3 2004 bercovitch l gastrointestinal 306 66 1988 neldner kh gastrointestinal and brain 100 8 discussion https://sciwheel.com/work/citation?ids=11604906&pre=&suf=&sa=0&dbf=0 https://sciwheel.com/work/citation?ids=11604911&pre=&suf=&sa=0&dbf=0 https://sciwheel.com/work/citation?ids=11604911&pre=&suf=&sa=0&dbf=0 https://sciwheel.com/work/citation?ids=11604913&pre=&suf=&sa=0&dbf=0 https://sciwheel.com/work/citation?ids=11604918,11609739,11604920&pre=&pre=&pre=&suf=&suf=&suf=&sa=0,0,0&dbf=0&dbf=0&dbf=0 skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 11 strategies can be used to minimize that adverse outcome. for example, the avoidance of blood thinners, aspirin and other non-steroidal anti-inflammatory drugs (nsaids) should be considered given these risks. other activities known to be associated with gastrointestinal bleeding such as heavy alcohol consumption, cigarette smoking, and dual antiplatelet therapy should be avoided. periodic checks of the stool for blood should be considered as part of the routine examination of patients with pxe. because of the known risk of retinal bleeding and intracranial hemorrhage, trauma to the head should be avoided, and certain sports such as boxing or soccer may not be ideal for patients with pxe. figure 4. calcified elastic fibers in the dermis of a patient with pxe in summary, pxe is associated with bleeding from many sites. while retinal bleeding is most common, there are many reports of gastrointestinal followed by bleeding in the brain. clinicians and patients should be made aware of the risk of these significant complications, to facilitate preventive measures, prompt recognition and treatment. conflict of interest disclosures: none funding: none corresponding author: lily lebwohl the leffell school 555 w hartsdale ave, hartsdale, ny 10530 email: lilylebwohl@gmail.com references: 1. ringpfeil f, lebwohl mg, christiano am, uitto j. pseudoxanthoma elasticum: mutations in the mrp6 gene encoding a transmembrane atp-binding cassette (abc) transporter. proc natl acad 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2019;30(suppl):536–537. 5. migden mr et al. j clin oncol. 2019;37(suppl):6015. 6. migden mr et al. lancet oncol. 2020;21:294–305. 7. eisenhauer et al. eur j cancer. 2009;45:228–247. 8. aaronson nk et al. j natl cancer inst. 1993;85:365–376. 9. osoba d et al. j clin oncol. 1998;16:139–144. funding sources funding was provided by regeneron pharmaceuticals, inc. and sanofi. acknowledgments the authors would like to thank the patients, their families, all other investigators, and all investigational site members involved in this study. the study was funded by regeneron pharmaceuticals, inc., and sanofi. medical writing support was provided by e. jay bienen, phd, and typesetting was provided by jenna lee, of prime, knutsford, uk, funded by regeneron pharmaceuticals, inc. and sanofi. for any questions regarding this poster presentation, please contact dr michael r migden, mrmigden@mdanderson.org disclosures michael r. migden: honoraria and travel expenses from regeneron pharmaceuticals, inc., sanofi, novartis, genentech, eli lilly and sun pharma; and institutional research funding from regeneron pharmaceuticals, inc., novartis, genentech and eli lilly. danny rischin: institutional research grant and funding from regeneron pharmaceuticals, inc., roche, merck sharp & dohme, bristol-myers squibb and glaxosmithkline; uncompensated scientific committee and advisory board from merck sharp & dohme, regeneron pharmaceuticals, inc., sanofi, glaxosmithkline and bristol-myers squibb; travel and accommodation from merck sharp & dohme and glaxosmithkline. stacie hudgens: consulting fees from regeneron pharmaceuticals, inc. chrysalyne d. schmults: steering committee member for castle biosciences; a steering committee member and consultant for regeneron pharmaceuticals, inc.; a consultant for sanofi; has received research funding from castle biosciences, regeneron pharmaceuticals, inc., novartis, genentech and merck, and is a chair for the national comprehensive cancer network. anna c. pavlick: honoraria and consulting or advisory roles at bristol-myers squibb, merck, regeneron pharmaceuticals, inc., array, novartis, seattle genetics and amgen; research funding from bristol-myers squibb, merck, regeneron pharmaceuticals, inc., celldex and forance and travel, accommodation, expenses from regeneron pharmaceuticals, inc., array and seattle genetics. alexander guminski: personal fees and non-financial support (advisory board and travel support) from bristol-myers squibb and sun pharma; personal fees (advisory board) from merck kgaa, eisai and pfizer; non-financial (travel) support from astellas; and clinical trial unit support from ppd australia. axel hauschild: institutional grants, speaker’s honoraria and consultancy fees from amgen, bristol-myers squibb, merck sharp & dohme/merck, pierre fabre, provectus, roche and novartis; institutional grants and consultancy fees from merck serono, philogen and regeneron pharmaceuticals, inc.; and consultancy fees from oncosec. chieh-i chen, zhen chen, vera mastey, matthew g. fury, israel lowy, siyu li: employees and shareholders of regeneron pharmaceuticals, inc. anne lynn s. chang: consulting and advisory roles at regeneron pharmaceuticals, inc. and merck; research funding from regeneron pharmaceuticals, inc., novartis, galderma and merck. guilherme rabinowits: consulting and advisory roles for emd serono pfizer, sanofi, regeneron pharmaceuticals inc. and merck and castle and stock/other ownership interests from syros pharmaceuticals and regeneron pharmaceuticals, inc. sherrif ibrahim: research funding from regeneron pharmaceuticals, inc. and castle, speakers’ bureau from genentech and travel and accommodation expenses from regeneron pharmaceuticals, inc. and genentech. denise bury, medha sasane: employees and shareholders of sanofi. summary and conclusion • these results support cemiplimab as a standard of care option for treatment of advanced cscc, with clinically meaningful benefits on hrqol and clinically meaningful reductions in pain that appear to be independent of opioid use and may correlate with tumor response. synopsis • patients with advanced cutaneous squamous cell carcinoma (cscc) who are not curable by surgery are generally administered palliative systemic therapy. in these patients, pain is an important symptom from the patient and clinician perspectives.1 • cemiplimab is indicated for treatment of patients with metastatic cscc (mcscc) or locally advanced cscc (lacscc) not eligible for curative surgery/radiation.2 • cemiplimab demonstrated a robust clinical response and a safety profile consistent with other checkpoint inhibitors.3 • a phase 2 clinical trial supported durability of response and reported an overall objective response rate (orr) of 46.1%4-6 as measured by response evaluation criteria in solid tumors version 1.1 (recist 1.1).7 • the phase 2 trial included the cancer-specific european organisation for research and treatment of cancer (eortc) 30-item questionnaire (qlq-c30)8 as a measure of patient-reported health-related quality of life (hrqol). 23 14 30 40 35 14 56 16 44 47 23 28 28 30 51 60 77 60 53 60 72 28 79 30 30 58 58 49 56 40 16 9 9 7 5 14 16 5 26 23 19 14 23 14 9 improvement maintenance deterioration cycle 12 (n=43) 13 7 22 28 31 19 43 11 37 35 23 26 28 23 43 75 88 64 62 51 71 41 78 31 49 55 59 40 56 40 12 5 14 10 18 10 17 11 33 17 22 15 33 21 18 0 20 40 60 80 100 global health status/hrqol physical function role function emotional function cognitive function social function fatigue nausea/vomiting pain dyspnea insomnia appetite loss constipation diarrhea financial problems patients (%) 0 20 40 60 80 100 patients (%) cycle 6 (n=101) figure 1. proportion of patients reporting clinically meaningful change at cycle 6 and cycle 12 cemiplimab improves health-related quality of life (hrqol) and reduces pain in patients with advanced cutaneous squamous cell carcinoma (cscc): results from a post hoc exploratory analysis of a phase 2 clinical trial michael r. migden,1 danny rischin,2 medha sasane,3 vera mastey,4 anna pavlick,5 chrysalyne d. schmults,6 zhen chen,4 alexander guminski,7 axel hauschild,8 denise bury,9 stacie hudgens,10 anne lynn s. chang,11 guilherme rabinowits,12 sherrif ibrahim,13 matthew g. fury,4 israel lowy,4 siyu li,14 chieh-i chen4 1university of texas md anderson cancer center, houston, tx, usa; 2peter maccallum cancer centre, melbourne, australia; 3sanofi, bridgewater township, nj, usa; 4regeneron pharmaceuticals, inc., tarrytown, ny, usa; 5new york university langone medical center, new york, ny, usa; 6brigham and women’s hospital, harvard medical school, boston, ma, usa; 7royal north shore hospital, sydney, australia; 8schleswig-holstein university hospital, kiel, germany; 9sanofi, cambridge, ma, usa; 10clinical outcomes solutions, tucson, az, usa; 11stanford university school of medicine, redwood city, ca, usa; 12miami cancer institute/baptist health south florida, miami, fl, usa; 13rochester medical center, rochester, ny, usa; 14regeneron pharmaceuticals, inc., basking ridge, nj, usa table 1. demographic and clinical characteristics of the full analysis set variable total (n=193) mcscc 350 mg q3w (n=56) mcscc 3 mg/kg q2w (n=59) lacscc 3 mg/kg q2w (n=78) age, mean ± sd, years 71.1 ± 11.4 69.7 ± 12.8 70.4 ± 10.1 72.5 ± 11.2 ≥65 years, n (%) 144 (74.6) 42 (75.0) 43 (72.9) 59 (75.6) male, n (%) 161 (83.4) 48 (85.7) 54 (91.5) 59 (75.6) ecog performance status, n (%) 0 86 (44.6) 25 (44.6) 23 (39.0) 38 (48.7) 1 107 (55.4) 31 (55.4) 36 (61.0) 40 (51.3) primary site, n (%) head and neck 131 (67.9) 31 (55.4) 38 (64.4) 62 (79.5) other 62 (32.1) 25 (44.6) 21 (35.6) 16 (20.5) prior cancer-related systemic therapy, n (%) 65 (33.7) 20 (35.7) 33 (55.9) 12 (15.4) prior cancer-related radiotherapy, n (%) 131 (67.9) 38 (67.9) 50 (84.7) 43 (55.1) sd, standard deviation. • clinically meaningful improvement or stability was experienced by 77%–86% of patients across qlq-c30 scales by cycle 6, and by 74%–95% at cycle 12 (figure 1). presented at the 2021 winter clinical dermatology conference, january 15–20, 2021, virtual scientific meeting. *p<0.0001 vs baseline 10 5 0 −5 −10 −15 −20 −25 baseline 2 3 4 5 6 7 8 9 10 11 12 l s m e a n ± s e c h a n g e f ro m b a s e lin e i n p a in s c o re ; lo w e r s c o re = b e tt e r o u tc o m e cycle (day 1) 137 125 105 105 101 84 73 65 59 52 43n=152total 57 47 35 33 29 25 23 18 15 12 7n=67clinical non-responders 80 78 70 72 72 59 50 47 44 40 36n=85clinicalresponder total clinical responders clinical non-responders 0 0.0 −2.7 −8.0* −13.0* −8.3 −11.5* −14.7* −1.7 −9.7* −14.9* −8.1 −12.1* −15.0* −0.22 −10.7* −15.8* −1.3 −13.4* −18.9* −8.6 −16.3* −19.9* 0.4 −13.8* −19.9* −0.9 −13.6* −18.7* −9.5 −18.2* −21.7* 0.1 −14.3* −18.3* figure 2. change from baseline in qlq-c30 pain score by cycle among patients who had baseline and post-baseline assessment of the qlq-c30 pain scale horizontal broken line indicates threshold for a clinically meaningful change. 140 130 120 110 100 90 2 3 4 5 6 7 8 9 10 11 12 r a te o f o p io id u se , c u m u la ti ve d a ys p e r p a ti e n tye a r ± 9 5 % c i clinical responders (n=85)total (n=152) cycle (day 1) 126.7 117.7 120.0 110.7 114.8 107.7 110.7 101.2 111.6 102.8 112.6 105.1 110.7 100.1 110.3 98.5 110.2 97.4 109.8 96.2 109.5 95.1 figure 3. cumulative number of days on opioids over time among patients who had baseline and post-baseline assessment of the qlq-c30 pain scale ci, confidence interval. 1.0 0.8 0.6 0.4 0.2 0 k m e s ti m a te o f c u m u la ti ve i n c id e n c e time to response (week) + censored a) clinically meaningful improvement (n=100) 1.0 0.8 0.6 0.4 0.2 0p ro b a b ili ty o f re s p o n s e c o m p le te r e s p o n s e / p a rt ia l re s p o n s e time to response (week) 1 15 30 45 60 75 90 105 b) first tumor response (n=85) 1 15 30 45 60 75 90 105 figure 4. km survival analysis of time to first clinically meaningful improvement in pain score (a) and first tumor response (b) time point where horizontal broken line (50% survival probability) crosses curve indicates median time to response. a) clinically meaningful deterioration (n=142) 1.0 0.8 0.6 0.4 0.2 0 p ro b a b ili ty o f p f s time to response (week) 1 15 30 45 60 75 90 105 120 135 150 165 b) pfs (n=193) 1.0 0.8 0.6 0.4 0.2 0 k m e s ti m a te o f c u m u la ti ve i n c id e n c e time to response (week) + censored 1 15 30 45 60 75 90 105 120 135 150 165 figure 5. km survival analysis of time to first clinically meaningful deterioration in pain score (a) and pfs (b) time point where horizontal broken line (50% survival probability) crosses curve indicates median time to response. table 3. summary of relationship between clinically meaningful changes in pain and clinical response among patients with cscc treated with cemiplimab* clinical responders (complete + partial) clinical nonresponders (stable + progressive) all baseline pain score, mean ± sd (n) 26.5 ± 29.1 (85) 33.7 ± 31.1 (83) 30.1 ± 30.3 (168) change from baseline in pain score at first tumor response, n 85 67 — ls mean change ± se –15.2 ± 1.5† –3.9 ± 2.1 — ls mean (95% ci) difference vs non-responders –11.3 (–16.3, –6.3)‡ — — median time to clinical response, months (n) 2.0 (85) — — median pfs, months (n) — — 18.4 (193) median time to first pain improvement, months (n) 2.1 (53) — 2.1 (100) median time to first pain deterioration, months (n) 20.6 (80) — 14.8 (142) *ns reflect the number of patients who had baseline and post-baseline assessment scores on the qlq-c30 pain scale. †p<0.0001 relative to baseline; ‡p<0.0001 compared with non-responders. • since pain medication use was captured over treatment duration, opioids were analyzed at each cycle. opioid use was adjusted for duration to calculate cumulative number of days on opioids per patient-year using poisson regression with treatment group as fixed factors and patients’ treatment exposure duration as offset variable. table 2. baseline scores and change from baseline (mmrm) in patients in the full analysis set who had baseline and post-baseline assessments on each qlq-c30 scale or item qlq-c30 scale/item baseline, mean ± sd (n) ls mean change ± se (n) cycle 3 cycle 12 global health status/hrqol 65.1 ± 22.9 (150) 7.8 ± 1.6 (122)** 11.1 ± 2.6 (43)** functional scales† physical function 80.1 ± 22.8 (151) 1.1 ± 1.3 (124) 4.0 ± 2.1 (43) role function 75.8 ± 30.0 (151) 0.4 ± 2.1 (123) 5.6 ± 3.4 (43) emotional function 80.2 ± 21.2 (151) 4.2 ± 1.3 (123)* 5.3 ± 2.2 (43)* cognitive function 83.4 ± 22.2 (151) 1.7 ± 1.4 (123) 2.5 ± 2.3 (43) social function 74.4 ± 31.8 (150) 5.3 ± 1.8 (122)* 8.6 ± 3.0 (43)* symptoms‡ fatigue 30.2 ± 24.6 (152) –2.8 ± 1.7 (125) –4.8 ± 2.8 (43) nausea/vomiting 4.6 ± 12.2 (152) –1.6 ± 0.8 (125)* –2.9 ± 1.3 (43)* pain 29.8 ± 30.4 (152) –11.5 ± 1.9 (125)** –14.3 ± 3.1 (43)** dyspnea 12.9 ± 23.4 (152) 0.7 ± 1.7 (125) 1.5 ± 2.9 (43) insomnia 27.4 ± 28.0 (151) –9.1 ± 2.0 (123)** –17.4 ± 3.3 (43)** appetite loss 19.5 ± 29.3 (152) –8.4 ± 1.6 (124)** –13.7 ± 2.7 (43)** constipation 13.6 ± 24.1 (152) –4.5 ± 1.5 (125)* –11.2 ± 2.5 (43)** diarrhea 4.9 ± 13.6 (150) 3.6 ± 1.4 (121)* 0.6 ± 2.3 (43) financial difficulty 19.1 ± 30.7 (150) 0.5 ± 2.0 (122) –3.4 ± 3.3 (43) **p<0.001 and *p<0.05 versus baseline. †higher scores reflect better outcomes. ‡lower scores reflect better outcomes. • baseline scores indicated moderate to high levels of functioning and moderate to low symptom burden (table 2). • at cycle 3, significant improvements from baseline were observed for emotional and social function and symptoms of pain, insomnia, appetite loss, nausea/vomiting, and constipation (all p<0.05) (table 2). • improvements increased or were maintained at cycle 12 and were clinically meaningful for pain, insomnia, appetite loss, and constipation (table 2). • these improvements likely contributed to the improved hrqol that was significant at cycle 3 (p<0.001) and clinically meaningful at cycle 12. • in all patients, reductions from baseline in pain were statistically significant as early as cycle 2, clinically meaningful by cycle 3, and sustained to cycle 12 (figure 2). • in contrast to clinical non-responders, clinical responders reported a clinically meaningful reduction in pain from baseline at cycle 2 with further reductions that were sustained to cycle 12 (all p<0.0001) (figure 2). • opioid use decreased over study duration (figure 3), suggesting that clinically meaningful improvement in pain was independent of opioid use. • median time to first clinically meaningful pain improvement in all patients approximated the median time to first tumor response that was estimated for clinical responders, 2.0 months and 2.1 months, respectively (figure 4; table 3). among clinical responders, the median time to first clinically meaningful pain improvement was also 2.1 months. • the change from baseline in pain score at first tumor response was statistically significant and clinically meaningful versus non-responders (p<0.0001) (table 3). study limitations • this was a single-arm, open-label study. • the 10-point threshold considered indicative of a clinically meaningful change has not been validated for this patient population (i.e., advanced cscc). • median time to first clinically meaningful deterioration in pain approximated the median time to progression-free survival (pfs), 14.8 months and 18.4 months, respectively (figure 5; table 3). median time to first clinically meaningful pain deterioration among clinical responders was 20.6 months (table 3). objective • this post hoc analysis explored the effects of cemiplimab on hrqol and pain using qlq-c30 data from the phase 2 clinical trial (nct02760498) of advanced cscc, with a focus on the association between time to clinically meaningful changes in pain and clinical tumor response. methods • for inclusion in this non-randomized, global, pivotal trial, adults with advanced cscc not amenable to curative surgery/radiotherapy according to the investigator were required to have ≥1 lesion, eastern cooperative oncology group (ecog) performance status ≤1, and life expectancy >12 weeks. • patients (n=193) received intravenous cemiplimab 3 mg/kg every 2 weeks (q2w; mcscc n=59; lacscc n=78) for 12 treatment cycles or 350 mg every 3 weeks (q3w; mcscc n=56) for six treatment cycles. treatment cycle length was 8 weeks for the q2w groups and 9 weeks for the q3w group. • the qlq-c308 was administered at baseline and day 1 of each treatment cycle. • the qlq-c30 assesses hrqol over the past week using a global health status/ hrqol scale and across functional domains (physical, role, cognitive, emotional, and social functioning) and symptoms (fatigue, pain, nausea/vomiting, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). scores range from 0 to 100; high scores on functional domains and low scores on symptoms reflect better outcomes. a change ≥10 points from baseline is considered clinically meaningful.9 • mixed-effects repeated measures models (mmrm) estimated changes from baseline to each cycle on all qlq-c30 scales; results are expressed as least squares (ls) mean and standard error (se). the model included fixed effects of treatment, visit, treatment-by-visit interaction, and baseline value. • changes from baseline in pain were also stratified by clinical responders, defined by orr assessed by independent central review, and clinical non-responders (stable or progressive disease). • for patients with data from baseline to cycle 6 and cycle 12, proportions with clinically meaningful (≥10 points) improvement or worsening, or stability (<10 points) on each item was determined. • kaplan–meier (km) survival analysis was used to estimate time to first clinically meaningful change in qlq-c30 pain score and its relationship to tumor response in patients who had baseline pain scores that allowed for at least a 10-point change. results • demographic characteristics of enrolled patients (n=193) were generally similar across treatment groups (table 1). powerpoint presentation while psoriasis is most commonly thought to be an adult disease, studies show that approximately 30% of cases begin in childhood, with a current incidence approximately 205/100,000 in the adolescent population.1,2 while there is consensus among clinicians that early treatment may help to prevent long-term psychosocial impact in adolescent patients, there is a general lack of clinical trial data and few approved medications in this age group, limiting treatment options.2,3 topical therapies such as corticosteroids are commonly used, but there is concern regarding long term side effects, especially the risk of adrenal suppression with the more potent corticosteroids.3 a novel foam formulation of halobetasol propionate (hbp), 0.05%, was approved by the fda in 2019 for the treatment of plaque psoriasis in adult patients, having been proven efficacious and well tolerated at doses of 3.5 grams per application with minimal systemic exposure and a favorable safety profile in patients 18 years and older.4 the data shown here are the results of an adrenal safety and pharmacokinetic (pk) study of the hbp foam in adolescent patients with plaque psoriasis introduction results patient compliance was monitored via diaries and weighing of product cans, and compliance was determined to be completion of at least 80% of expected applications. • 24 subjects* aged 12 to <18 years with stable plaque psoriasis on at least 10% bsa (excluding face, scalp, groin, axillae, and other intertriginous areas), and an iga of at least 3 (moderate) were instructed to apply hbp foam twice daily (approximately 12 hours apart) to all psoriatic plaques identified at baseline for up to 2 weeks, or until the investigator verified subjects’ psoriasis had cleared. • at screening, day 15, and 4 weeks post end of study (eos) hpa axis response to cosyntropin stimulation test (cst) was assessed. • plasma concentrations of hbp were measured at screening, day 8, and day 15. • changes in investigator’s global assessment (iga) were at screening, baseline visit/day 1, day 8, and day 15. • % body surface area (bsa) was estimated at baseline visit/day 1, day 8, and day 15/eos. • patient compliance with the prescribed treatment regimen also assessed at each follow-up visit. • adverse events, local skin reactions associated with topical application of corticosteroids (telangiectasia, skin atrophy, burning/stinging, and folliculitis), laboratory tests (chemistry, hematology, and urinalysis), and urine pregnancy tests were also assessed throughout the study. table 1: baseline demographics phase iv open label evaluation of the adrenal suppression potential and pharmacokinetic properties of twice daily halobetasol propionate foam, 0.05% in adolescent subjects with plaque psoriasis adelaide a. hebert, mda; rhonda schreiber msrnb; debbie glaab msn, cpnp-acb; lawrence f. eichenfield, mdc methods teaes n(%) relationship to treatment seriousness abnormal acth stimulation test 1 (4.2) related mild abnormal acth stimulation test 5 (20.8) possibly related mild gastritis 1 (4.2) not related moderate hematuria 1 (4.2) not related mild table 3: treatment emergent adverse events (teaes) figure 1: % patients with iga reduction at each study visit laboratory evidence of hpa axis suppression, as evidenced by post-cst serum total cortisol level of ≤ 18μg/dl, was noted in 6 of 23 patients at day 15 and resolved by the post-eos study visit, ~4 weeks later. none of these had any clinical features of adrenal suppression and only 3 had measurable hbp plasma trough levels. in these 3 patients, no correlation was found between %bsa treated or average amount of product used and adrenal suppression or measurable hbp plasma trough levels. overall, 9 patients of 23 had measurable plasma trough hbp levels at day 15. the %bsa treated and average amount of product used was comparable for all study patients, including those with laboratory evidence of hpa suppression and measurable hbp plasma trough levels. by day 15, 95.5% of the 23 patients who were evaluated had at least a 1-grade improvement in iga, 50% had a 2-grade improvement, and 22.7% a 3-grade improvement from baseline. the mean %bsa affected with disease showed a 1.9% decrease from baseline at day 8 and a 6% decrease by day 15. all patients met the dosing compliance criterion of at least 80% and no more than 120% of the expected number of applications being applied. no serious safety issues were noted from ae/lsr evaluations, and mean changes for all clinical laboratory values were within expected limits of normal variation. gender n(%) iga n(%) female 11 (45.8) 3-moderate 22 (91.7) male 13 (54.2) 4-severe 2 (9.3) ethnicity n(%) % bsa mean (range) hispanic or latino 6 (25) affected 15.1 (11-23) not hispanic or latino 18 (75) to be treated 14.5 (10-20) race n(%) age mean (range) white 24 (100) years 14.7 (12.1-17.7) hbp foam was well tolerated with improvement in both iga and bsa and good patient compliance. no serious adverse events were reported and no patients discontinued due to side effects. laboratory evidence of adrenal suppression was seen in few patients and was transient, with no accompanying clinical signs of hpa axis suppression. systemic exposure to hbp was minimal and did not correlate to adrenal suppression, bsa treated, nor the amount of product used. results of this study support the safety, tolerability, and efficacy of hbp foam, 0.05% in treating psoriasis in adolescent patients and fda approval for ages 12+ was received in august of 2021. conclusions references 1. bronker et al. psoriasis in children and adolescents: diagnosis, management and comorbidities. pediatr drugs (2015) 17:373–384. doi 10.1007/s40272-015-0137-1. 2. paller et al. prevalence of psoriasis in children and adolescents in the united states: a claims-based analysis. j drugs dermatol. 2018;17(2):187-194. 3. thomas et al. treating pediatric plaque psoriasis: challenges and solutions. pediatric health, medicine and therapeutics 2016:7 25–38. 4. bhatia et al. two multicenter, randomized, double-blind, parallel group comparison studies of a novel foam formulation of halobetasol propionate, 0.05% vs its vehicle in adult subjects with plaque psoriasis. j drugs dermatol. 2019 aug 1;18(8):790-796. disclosures & affiliations a. departments of dermatology and pediatrics, the uthealth mcgovern medical school, houston b. ms. schreiber and ms. glaab are employed by mayne pharma. c. departments of dermatology and pediatrics, university of california, san diego school of medicine, and rady children's hospital, san diego, ca. this study was sponsored by mayne pharma. • primary objective was to determine adrenal axis suppression potential and pk of hbp foam, 0.05% applied bid up to 2 weeks in patients age 12-17 years with stable plaque psoriasis. objectives none of the teaes were serious, none were within the treatment area, none required a change in test article dosing or discontinuation from the study, and all teaes recovered/resolved by eos lsrs day 1 – pre dose n(%) day 8 n(%) day 15 n(%) telangiectasia 6 (25) 6 (25) 6 (26.1) skin atrophy 6 (25) 6 (25) 4 (17.4) table 2: localized skin reactions (lsrs) burning/stinging and folliculitis were absent for all subjects at all visits. with the exception of 1 case of severe telangiectasia at baseline prior to test article application, all other cases of telangiectasia and skin atrophy were moderate or mild in severity during the study. telangiectasia and skin atrophy were observed in 6 subjects; all from the same study site. there were no subjects who had an lsr that worsened during the study. compliant n(%) yes 23(100) no 0(0) dosing mean (min, max) number of days dosed 14.1 (9,17) number of applications 28.3 (18,43) % of expected doses applied 100.6 (92.9, 107.1) table 1: dosing compliance *one patient was excluded from the evaluable and pk populations due to use of prohibited medication. 30.4% 52.2% 13.0% 4.3%4.5% 22.7% 50.0% 22.7% no change 1-grade improvement 2-grade improvement 3-grade improvement day 8 day 15 figure 2: % bsa affected over time 15.1% 12.7% 9.1% baseline day 8 day 15/eos *one subject was excluded from the evaluable and pk populations due to use of a prohibited medication figure 1: % patients with iga reduction at each study visit 30.4% 52.2% 13.0% 4.3%4.5% 22.7% 50.0% 22.7% no change 1-grade improvement 2-grade improvement 3-grade improvement day 8 day 15 internal use mark lebwohl, md1; darrell rigel, md, ms1; todd schlesinger, md2; april armstrong, md3; brian berman, md, phd4; neal bhatia, md5; james del rosso, do6; leon kircik, md1; vishal a. patel, md7; siva narayanan, phd8; volker koscielny, md9; ismail kasujee phd9 1mount sinai icahn school of medicine, new york, ny, usa; 2clinical research center of the carolinas, charleston, sc, usa; 3keck school of medicine, university of southern california, los angeles, ca, usa; 4university of miami miller school of medicine, miami, fl, usa; 5therapeutics clinical research, san diego, ca, usa; 6jdr dermatology research/thomas dermatology, las vegas, nv, usa; 7george washington school of medicine and health sciences, washington, dc, usa; 8avant health llc, bethesda, md, usa; 9almirall sa, barcelona, spain. comparison of patient and clinician satisfaction with tirbanibulin treatment’s ability to improve ‘how skin looks’ and ‘skin texture’ in the treated area, among patients with actinic keratosis treated with tirbanibulin in community practices across the u.s (proak study) introduction: the objective of this analysis was to compare patient and clinician satisfaction with tirbanibulin treatment’s ability to improve ‘how skin looks’ and ‘skin texture’ in the treated area, among patients with actinic keratosis (ak) treated with tirbanibulin in community practices across the u.s. methods: a single-arm, prospective cohort study (proak) was conducted among adult patients with aks on the face or scalp who were newly initiated with once-daily tirbanibulin treatment (5-day course) in real-world community practices in the u.s, as part of usual care. patients and clinicians completed surveys and clinical assessments at baseline, week-8 (timeframe for main endpoints) and week-24. patient’s self-reported satisfaction and clinician satisfaction with tirbanibulin treatment’s ability to improve ‘how skin looks’ and ‘skin texture’ in the treated area at individual patient-level were assessed among study patients at week-8 on a sevenpoint adjectival response scale of 1 (extremely dissatisfied) – 7 (extremely satisfied). results: a total of 290 patients with aks completed the study assessments at week-8. patient self-reported skin-texture at baseline was – dry: 39.66%, smooth: 47.59%, rough: 19.66%, bumpy: 18.62%, scaly: 35.17%, blistering/peeling: 6.55%. all patients (100%) completed their 5-day oncedaily treatment course. at week-8, 75.86% & 78.97% of the patients and clinicians respectively reported extremely/very/satisfied with tirbanibulin’s ability to improve ‘how skin looks’, while 14.14% & 14.14% respectively reported somewhat satisfied, and 10.00% & 6.55% respectively reported extremely/very/dissatisfied. at week-8, 74.83% & 80.69% of patients and clinicians respectively reported extremely/very/satisfied with tirbanibulin’s ability to improve their ‘skin texture’, while 15.52% & 12.41% respectively reported somewhat satisfied, and 9.65% & 6.55% respectively reported extremely/very/dissatisfied. conclusion: majority of patients with aks and their clinicians reported satisfaction with the ability of 5-day treatment course of tirbanibulin to improve ‘how skin looks’ or ‘skin texture’ in the tirbanibulin-treated area, at week-8. synopsis conclusions • a majority of patients with aks and their clinicians reported satisfaction with the ability of 5-day treatment course of tirbanibulin to improve ‘how skin looks’ or ‘skin texture’ in the tirbanibulin-treated area, at week-8. • the demonstrated effectiveness and the safe and tolerable profile of once-daily tirbanibulin treatment highlights the benefits associated with this novel therapeutic option in routine community practice settings, for optimal management of aks. sponsored by almirall, s.a. methods • a single-arm, prospective cohort study was conducted among adult patients with aks on the face or scalp who were newly initiated with oncedaily tirbanibulin treatment (5-day course) in real-world community practices in the u.s, as part of usual care. • a total of 300 subjects were enrolled from 32 community practices across the u.s. • main treatment assessment timepoints were at baseline and week-8, while patients were followed for up to week-24. • subjects completed self-assessment questions at baseline and week8 about their skin appearance and texture. • clinicians completed surveys and clinical assessments at baseline and week-8, concerning attributes and effectiveness of tirbanibulin. • patient and clinician satisfaction was assessed at week-8 concerning the ability of tirbanibulin treatment to ‘improve how skin looks’ and ‘improve skin texture’ in comparison to baseline. • patients and clinicians reported satisfaction in individual patient treatment outcomes in the tirbanibulin-treated area (compared to baseline), using a seven-point adjectival response scale of 1 (extremely dissatisfied) – 7 (extremely satisfied). • patient and clinician reported outcomes were analyzed descriptively using data from week-8, for all study patients with available data, as observed. objective • the objective of this analysis was to compare patient and clinician satisfaction with tirbanibulin treatment’s ability to improve ‘how skin looks’ and ‘skin texture’ in the treated area, among patients with actinic keratosis (ak) treated with tirbanibulin in community practices across the u.s results • proak study (nct05260073) was initiated in 2022, with more than 75% of the study patients treated with tirbanibulin between april and august of 2022. • out of 300 enrolled patients, a total of 290 patients with aks completed the study assessments at week-8, and hence included in the analyses. • all patients (100%) completed their 5-day once-daily treatment course. • ten patients were not included in the week-8 analyses: 1 patient had missing data, and 9 patients were discontinued from the study due to patient voluntary withdrawal of consent or lost to follow-up. • no discontinuations were related to adverse drug reactions (adrs), and there were no serious adrs reported at week-8. table 1: baseline patient characteristics n=290 age, mean years [min, max] 66.30 [30.00, 90.00] gender, % femalemale 31.38 68.62 primary health insurance, % private insurance medicaid medicare uninsured 41.72 3.10 53.79 1.38 history of skin cancer, % 61.72 fitzpatrick skin type, % type i type ii type iii type iv type v 7.59 71.38 18.62 1.38 1.03 baseline patient selfreported skin-texture, % dry smooth rough bumpy scaly blistering peeling 39.66 47.59 19.66 18.62 35.17 0.34 6.21 baseline severity of skin photodamage in ak affected area, % absent mild moderate severe 1.03 21.38 56.55 20.34 6.55% 14.14% 78.97% 10.00% 14.14% 75.86% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% extremely/very/dissatisfied somewhat satisfied extremely/very/satisfied p ro po rti on o f p at ie nt s at w ee k8 satisfaction ratings figure 1: majority of patients and clinicians were ‘extremely/very /satisfied’ with how skin looks, after the 8-week treatment course clinician patient table 2: site characteristics (n=32) current workplace: private, office-based practice, % 100 total number of board-certified dermatologists in the clinic/practice, mean 3.53 number of patients with aks managed by the clinic in a given month, mean 136.34 number of years practicing dermatology, mean 15.66 n = 290 6.55% 12.41% 80.69% 9.65% 15.5… 74.83% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% extremely/very/dissatisfied somewhat satisfied extremely/very/satisfied p ro po rti on o f p at ie nt s at w ee k8 satisfaction ratings figure 2: majority of patients and clinicians were ‘extremely/very /satisfied’ with skin texture, after the 8-week treatment course clinician patientn = 290 skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 381 in-depth reviews impact of depression on health-related quality of life among skin cancer survivors kaustuv bhattacharya, ms,1 namita joshi, phd,2 ruchit shah, phd,2 vinayak k. nahar, md, phd, ms, frsph3,4 1department of pharmacy administration, university of mississippi, university, ms 2pharmerit international, bethesda, md 3department of dermatology, school of medicine, university of mississippi medical center, jackson, ms 4department of preventive medicine, school of medicine/john d. bower school of population health, university of mississippi medical center, jackson, ms abstract introduction: skin cancers are one of the most common cancers in the united states (us). studies have reported depression to be a common comorbid condition among individuals with skin cancer. this study aimed to evaluate the relationship of depression with health-related quality of life (hrqol) among individuals with a skin cancer diagnosis. methods: a cross-sectional study design using the 2017 behavioral risk factor surveillance system (brfss) data, a nationally representative sample of non-institutionalized us adults, was utilized for the study. multivariable logistic regression was used to assess the relationship between depression and the hrqol domains (general health status, physical health, mental health, and activity limitations due to poor physical or mental health) among survivors of skin cancer. results: comorbid depression was identified in 20% of skin cancer survivors. after adjusting for covariates, skin cancer survivors with depression had higher odds of having poor general health status (odds ratio [or] = 1.67, 95% confidence interval [ci] 1.41-1.98) as compared to skin cancer survivors without depression. skin cancer survivors with depression also had greater odds of having poor physical hrqol (or = 1.82, 95% ci 1.53-2.15), poor mental hrqol (or = 6.38, 95% ci 5.26-7.74), and activity limitations (or = 2.42, 95% ci 2.03-2.89) as compared to those without depression. conclusion: this study highlights the significant negative impact of comorbid depression on hrqol in a nationally representative sample of skin cancer survivors and serves as evidence for the need for more active surveillance and management of depression in this population. skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 382 skin cancer is defined as unnatural growth of skin cells and usually develops on exposure to the sun. there are two major subtypes of skin cancer – melanoma and non-melanoma skin cancer (nmsc). skin cancer is the most prevalent cancer in the united states (us), and the incidence of both nmsc and melanoma has been rapidly increasing in recent years. it was estimated that over 5 million cases of nmsc are diagnosed every year in the us.1 according to american cancer society, in 2019, about 96,480 people in the us will be diagnosed with melanoma and there will be about 7,230 deaths from melanoma.2 previous studies have found skin cancer to greatly impact hrqol of patients. a systematic review of hrqol among melanoma patients reported the disease to impact hrqol at three specific stages melanoma diagnosis, treatment, and followup.3 in addition, studies using melanoma specific hrqol instruments reported a significant decrements in hrqol between patients with local/regional and advanced melanoma.4,5 while studies comparing hrqol between melanoma patients and that of the general population have often found no significant differences,6 melanoma patients have been found to have similar hrqol as that of patients with other malignancies, such as renal cell carcinoma.7 even though it does not have a significant risk of associated mortality, studies have shown nmsc to have a significant negative impact on the hrqol of a patient. previous studies of hrqol among patients with nmsc reported that previous studies have found that the domains of physical deformity, cosmesis, and psychosocial functioning were impacted by the disease.8,9 another study that assessed hrqol among young adults with nmsc reported concerns about their skin cancer and possibility of developing further cancers in the future as the domains most impacted by the disease.10 diagnosis of nmsc, its treatment, and the consequences of the treatment all contributed to its impact on hrqol.11 extant literature has identified depression to be a significant comorbidity in patients with skin cancer. a study reported that three out of every ten patients with melanoma had emotional distress (i.e., anxiety, depression, and adjustment disorder), a proportion that is comparable to the prevalence of emotional distress in patients with other cancers.12 a systematic review of psychological response among malignant melanoma patients also found a 30% prevalence of comorbid psychological distress,13 which was similar to that found in malignancies like breast and colon cancer.14 studies have reported anxiety and depression to be most common psychological disorders in this population.15 it has been seen that comorbid depression has a detrimental effect on patient qol and disease prognosis. a study by trask et al. examined the psychosocial characteristics of non-stage iv melanoma patients in a melanoma clinic in the us. the study results suggested that ~33% of the patients exhibited high levels of distress, and that the group of distressed patients had inferior qol compared with the non-distressed patient group. it also revealed that the group of distressed patients was more likely to use maladaptive (negative) coping strategies as compared to the non-distressed group of patients.16 several other studies have also found a strong association between comorbid depression and poor hrqol among adult cancer survivors.17–20 however, to our knowledge, there are no studies that have assessed the impact of comorbid depression on hrqol on introduction skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 383 survivors of skin cancer in a nationally representative sample of us adults. a nationally representative estimate of the burden of comorbid depression on hrqol amongst skin cancer survivors will be instrumental in helping policy-makers make decisions about depression management in this population. it will also help policy-makers better allocate healthcare resources geared towards screening and management of depression. study design and data: in this retrospective cross-sectional study, we analyzed the 2017 behavioral risk factor surveillance system (brfss) dataset for the study. brfss data is collected by joint collaboration of the center for disease control and prevention (cdc) and state health departments of the 50 states and territories on health risk behaviors, preventive health practices, and health care service use and access pertaining to chronic conditions. it is funded by the federal government and data is collected annually by state-based surveillance systems through telephone surveys. iterative proportional fitting is used to assign weights to brfss data in order for the sample to be considered nationally representative. public accessibility of the brfss data obviated the need for the study to be reviewed by the institutional review board at the university of mississippi. data regarding skin cancer, depression and hrqol was obtained from the 2017 brfss dataset to examine the study objectives. study variables: identification of individuals with a history of skin cancer was done based on their response to the question in the brfss questionnaire, “has a doctor, nurse, or other health professional ever told you that you had skin cancer?” individuals who responded with a yes were identified as skin cancer survivors. among skin cancer survivors, depression was identified based on an individual’s response (“yes” or “no”) to the question in the brfss questionnaire, “has a doctor, nurse, or other health professional ever told you that you have a depressive disorder, including depression, major depression, dysthymia, or minor depression?” four questions are used to measure hrqol in brfss. the four questions evaluate four aspects of hrqol, viz. general health status, physical hrqol, mental hrqol, and activity limitations attributed to poor physical or mental health. general health status was determined based on response (“excellent”, “very good”, “good”, “fair”, and “poor”) to the question in the questionnaire, “would you say that in general your health is ?” for the purpose of this study, the responses were dichotomized into good health (including “excellent”, “very good”, and “good”) and poor health (including “fair” and “poor”). physical hrqol was evaluated based on the response to the question in the questionnaire, “now thinking about your physical health, which includes physical illness and injury, for how many days during the past 30 days was your physical health not good?” mental hrqol was assessed based on the response to the question in the questionnaire, “now thinking about your mental health, which includes stress, depression, and problems with emotions, for how many days during the past 30 days was your mental health not good?” activity limitations due to poor physical and mental health was gauged based on the response to the question in the questionnaire, “during the past 30 days, for about how many days did poor physical or mental health keep you from doing your usual activities, such as self-care, work, or recreation?” we collapsed methods skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 384 responses for physical hrqol, mental hrqol, and activity limitations attributed to poor physical or mental health into two categories contingent upon whether the individuals were affected for less than 14 days (good) or greater than or equal to 14 days (poor). scoring of the four hrqol variables has been previously validated21, and it has been employed by studies that have assessed hrqol using brfss data.22 other covariates that were taken into consideration comprised of age, sex, race, income, geographic region, employment status, health insurance, marital status, education, and a count of chronic diseases. age was divided into three categories, for individuals between 18 and 44 years, for individuals between 45 and 64 years, and for individuals who are 65 years old and older. race was stratified into non-hispanic whites, non-hispanic blacks, hispanics, multiracial, and others. income was categorized as less than $10,000, between $10,000 and 19,999, between $20,000 and $34,999, between $35,000 and $74,999, and greater than or equal to $75,000. geographic regions were categorized as northeast, midwest, south, and west. employment status included unable to work, retired, student/homemaker, out of work, and employed. health insurance status was dichotomized contingent on individuals reporting any kind of healthcare coverage. marital status included never married, widowed, divorced or separated, and married or part of a couple. education status was categorized into less than high school, graduated high school, attended college or technical school, and college graduate. a count of chronic disorders was taken by adding the chronic conditions (myocardial infarction, coronary heart disease, stroke, asthma, other cancer, copd, arthritis, kidney disease, diabetes) reported to be present by individuals, other than skin cancer and depression. this has been done by previous studies that have utilized brfss data.22 study analyses: study analyses were conducted using sas version 9.4 (sas institute inc, cary, nc). proc survey procedures were used to account for brfss’s complex study design. proc surveyfreq and proc surveymeans were employed for comparison of frequencies and percentages of categorical and continuous variables. proc surveylogistic was used to conduct bivariate analyses and multivariable logistic regression to assess the relationship between depression and hrqol (general health status, physical hrqol, mental hrqol, and activity limitations due to physical and mental hrqol) among skin cancer survivors. odds ratios (ors) and confidence intervals (cis) were reported and results were considered statistically significant at p = 0.05. of the 450,016 adults who participated in the 2017 brfss survey, 42,045 (9.3%) were skin cancer survivors and constituted the final sample of interest. of the skin cancer survivors, 8,394 (20.0%) had a diagnosis of depression. patient demographic and clinical characteristics for skin cancer survivors with and without depression are shown in table 1. skin cancer survivors with depression were younger, predominantly female and nonwhite, had lower income, more likely to not be able to work, and less likely to be married than those without depression. they also had higher number of chronic comorbid conditions and were more likely to not have health insurance as compared to those without depression. results skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 385 the results from the bivariate analyses for the association between depression and the four hrqol variables (general health status, physical hrqol, mental hrqol, and activity limitations) have been presented in table 2. these were the unadjusted comparisons that did not account for any covariates. from the results of the bivariate analysis we can say that adult skin cancer survivors with depression had significantly greater odds of having poor general health status (or = 2.78, 95% ci 2.47-3.12), poor physical hrqol (or = 2.97, 95% ci 2.613.37), poor mental hrqol (or = 8.84, 95% ci 7.41-10.56), and activity limitations (or = 4.17, 95% ci 3.59-4.84) as compared to their non-depressed counterparts. table 3 presents results of the multivariable logistic regression analyses examining the impact of depression on the four hrqol variables (general health status, physical hrqol, mental hrqol, and activity limitations). after accounting for baseline demographics and comorbidities, adult skin cancer survivors with depression had greater odds of having poor general health status (or = 1.67, 95% ci 1.41-1.98) as compared to skin cancer survivors without depression. they also had higher odds of having poor (≥ 14 unhealthy days) physical hrqol (or = 1.82, 95% ci 1.53-2.15), poor mental hrqol (or = 6.38, 95% ci 5.26-7.74), and activity limitations (or = 2.42, 95% ci 2.032.89) versus those without depression. table 1. demographic and clinical characteristics of adult skin cancer survivors. behavioral risk factor surveillance system (brfss), 2017. characteristicsa total,b n (%) skin cancer with depression,c n (%) skin cancer without depression, n (%) p-value age <.001 18-44 1,409 (3.4) 416 (5.0) 993 (3.0) 45-64 11,448 (27.2) 3,099 (36.9) 8,349 (24.8) ≥65 29,188 (69.4) 4,879 (58.1) 24,309 (72.2) gender <.001 male 19,489 (46.4) 2,983 (35.6) 16,506 (49.1) female 22,532 (53.6) 5,401 (64.4) 17,131 (50.9) race/ethnicity <.001 white 39,540 (95.5) 7,729 (93.7) 31,811 (96.0) black 197 (0.5) 59 (0.7) 138 (0.4) hispanic 561 (1.4) 165 (2.0) 396 (1.2) multiracial 504 (1.2) 138 (1.7) 366 (1.1) othera 600 (1.4) 160 (1.9) 440 (1.3) income <.001 <$10 000 873 (2.5) 419 (5.8) 454 (1.6) skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 386 $10 000-$19 000 3,503 (10.1) 1,132 (15.7) 2,371 (8.6) $20 000-$34 999 6,850 (19.7) 1,656 (23.0) 5,194 (18.9) $35 000-$74 999 11,386 (32.8) 2,234 (31.0) 9,152 (32.2) ≥$75 000 12,149 (34.9) 1,767 (24.5) 10,382 (37.7) health plan <.001 no 957 (2.3) 285 (3.4) 672 (2.0) yes 41,016 (97.7) 8,092 (96.6) 32,924 (98.0) marital status <.001 never married 2,199 (5.2) 619 (7.4) 1,580 (4.7) widowed 9,066 (21.6) 1,695 (20.3) 7,371 (22.0) divorced 5,900 (14.1) 1,943 (23.2) 3,957 (11.8) married 24,737 (59.1) 4,106 (49.1) 20,631 (61.5) education <.001 less than high school 2,047 (4.9) 600 (7.2) 1,447 (4.3) high school graduate 10,064 (24.0) 2,051 (24.5) 8,013 (23.9) attended college / technical school 11,274 (26.9) 2,444 (29.2) 8,830 (26.3) college graduate 18,571 (44.2) 3,286 (39.1) 15,285 (45.5) employment <.001 unable to work 2,539 (6.1) 1,399 (16.7) 1,140 (3.4) retired 24,240 (57.9) 4,101 (49.1) 20,139 (60.1) student/homemaker 2,016 (4.8) 397 (4.7) 1,619 (4.8) out of work 1,047 (2.5) 351 (4.2) 696 (2.1) employed 12,051 (28.7) 2,111 (25.3) 9,940 (29.6) geographic region <.001 northeast 6,795 (16.2) 1,331 (15.9) 5,464 (16.3) midwest 11,138 (26.6) 2,105 (25.2) 9,033 (26.9) south 14,031 (33.4) 2,897 (34.6) 11,134 (33.2) west 9,975 (23.8) 2,028 (24.3) 7,947 (23.6) general health status <.001 good 32,308 (77.1) 5,017 (60.0) 27,291 (81.4) skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 387 poor 9,593 (22.9) 3,349 (40.0) 6,244 (18.6) physical hrqol <.001 good (< 14) 33,647 (82.0) 5,455 (66.7) 28,192 (85.8) poor (≥ 14) 7,386 (18.0) 2,722 (33.3) 4,664 (14.2) mental hrqol <.001 good (< 14) 37,510 (90.6) 5,638 (69.1) 31,872 (95.9) poor (≥ 14) 3,883 (9.4) 2,523 (30.9) 1,360 (4.1) activity limitations <.001 no (< 14) 36,947 (89.0) 6,093 (74.3) 30,854 (92.6) yes (≥ 14) 4,575 (11.0) 2,113 (25.7) 2,462 (7.4) number of chronic conditions, mean (± sd) 42,045 1.99 (0.02) 1.35 (0.01) <.001 a. other includes asians, native hawaiians, other pacific islanders, american indians, or alaska natives. b. the study sample included 42,045 adult skin cancer survivors c. 8,394 of the adult skin cancer survivors had depression all n indicate unweighted estimates hrqol, health-related quality of life; sd, standard deviation table 2. bivariate association between depression and general health status, physical hrqol, mental hrqol, and activity limitations among adult skin cancer survivors. behavioral risk factor surveillance system (brfss), 2017. odds ratio (95% confidence interval) p-value outcome variable depressed non-depressed general health status 2.78 (2.47-3.12) reference <.001 physical hrqol 2.97 (2.61-3.37) reference <.001 mental hrqol 8.84 (7.41-10.56) reference <.001 activity limitations 4.17 (3.59-4.84) reference <.001 hrqol, health-related quality of life table 3. multivariable logistic regression assessing relationship between depression and general health status, physical hrqol, mental hrqol, and activity limitations among adult skin cancer survivors. behavioral risk factor surveillance system (brfss), 2017. odds ratio (95% confidence interval) study variable general health status physical hrqol mental hrqol activity limitations depression no reference reference reference reference yes 1.67 (1.411.98) * 1.82 (1.532.15)* 6.38 (5.267.74)* 2.42 (2.032.89)* skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 388 odds ratio (95% confidence interval) study variable general health status physical hrqol mental hrqol activity limitations age 18 – 44 reference reference reference reference 45 – 64 1.10 (0.771.59) 0.95 (0.671.34) 0.61 (0.450.81)* 0.67 (0.450.99)* ≥65 0.77 (0.521.16) 0.69 (0.47-1) 0.44 (0.310.61)* 0.51 (0.330.78)* gender female reference reference reference reference male 1.27 (1.101.47)* 1.03 (0.88-1.2) 1.09 (0.891.32) 1.06 (0.9-1.26) race white reference reference reference reference black 1.47 (0.663.26) 1.06 (0.452.49) 1.34 (0.6-2.98) 1.41 (0.623.21) hispanic 0.99 (0.51.99) 0.68 (0.36-1.3) 1.16 (0.562.42) 0.53 (0.251.15) multiracial 1.07 (0.691.64) 1.32 (0.782.24) 1.28 (0.821.99) 0.98 (0.56-1.7) othera 0.89 (0.421.89) 1.45 (0.792.65) 1.46 (0.862.49) 1.55 (0.822.92) income <$10 000 reference reference reference reference $10,000$19,000 0.88 (0.581.34) 0.78 (0.521.15) 0.79 (0.5-1.25) 0.9 (0.58-1.4) $20,000$34,999 0.59 (0.390.89)* 0.49 (0.330.73)* 0.64 (0.391.03) 0.69 (0.441.09) $35,000$74,999 0.46 (0.30.7)* 0.37 (0.250.55)* 0.58 (0.350.96)* 0.57 (0.36-0.9)* ≥ $75,000 0.28 (0.180.44)* 0.27 (0.180.42)* 0.50 (0.290.85)* 0.43 (0.250.73)* health plan no reference reference reference reference yes 0.94 (0.641.4) 1.01 (0.671.52) 0.85 (0.611.18) 1.05 (0.721.53) marital status never married reference reference reference reference widowed 0.98 (0.691.38) 1.32 (0.921.89) 1.03 (0.691.53) 0.88 (0.59-1.3) divorced 1.11 (0.791.55) 1.25 (0.9-1.73) 0.95 (0.671.33) 1.04 (0.721.53) skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 389 odds ratio (95% confidence interval) study variable general health status physical hrqol mental hrqol activity limitations married 1.05 (0.761.44) 1.37 (1-1.89)* 0.74 (0.541.03) 0.9 (0.62-1.31) education less than high school reference reference reference reference high school graduate 0.67 (0.510.88)* 1.06 (0.81-1.4) 0.93 (0.671.29) 0.72 (0.540.98)* attended college/ technical school 0.48 (0.360.64)* 0.97 (0.72-1.3) 0.71 (0.510.99)* 0.76 (0.551.03) college graduate 0.41 (0.310.55)* 0.91 (0.681.23) 0.57 (0.40-0.8)* 0.69 (0.5-0.96)* employment unable to work reference reference reference reference retired 0.31 (0.230.43)* 0.25 (0.190.33)* 0.47 (0.340.65)* 0.25 (0.190.33)* student/ homemaker 0.25 (0.160.4)* 0.22 (0.150.34)* 0.42 (0.260.66)* 0.18 (0.120.29)* out of work 0.31 (0.210.45)* 0.43 (0.290.63)* 0.81 (0.55-1.2) 0.45 (0.310.65)* employed 0.20 (0.150.28)* 0.15 (0.110.21)* 0.44 (0.320.61)* 0.13 (0.090.18)* geographic region northeast reference reference reference reference midwest 0.91 (0.751.11) 0.99 (0.811.22) 0.81 (0.631.03) 0.92 (0.71-1.2) south 1.04 (0.851.27) 0.86 (0.7-1.06) 0.96 (0.751.23) 0.91 (0.7-1.18) west 0.88 (0.691.1) 0.95 (0.751.21) 0.89 (0.671.18) 0.91 (0.69-1.2) number of chronic conditions 1.80 (1.71.91)* 1.50 (1.421.58)* 1.15 1.13 (1.06-1.2)* 1.45 (1.371.53)* a. other includes asians, native hawaiians, other pacific islanders, american indians, or alaska natives. *signifies p value less than .05 hrqol, health-related quality of life. even though previous studies have assessed the relationship between depression and hrqol among skin cancer, none of them have been investigated in a sample representative of the us population. to the best of our knowledge, this is the first study discussion skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 390 to have assessed the burden of depression among skin cancer survivors in a nationally representative sample of us adults. specifically, the study compared hrqol among skin cancer patients with and without depression. this study estimated the prevalence rate of comorbid depression to be 20 % among skin cancer survivors. this is similar to findings in other studies. an assessment of current depression among melanoma survivors using the 2010 brfss data reported a prevalence of 17%.23 however, the data for this study was collected in only six states, limiting its generalizability at a national level. another study that collected data from a melanoma clinic in the us found that almost 30% of the melanoma patients were also suffering from high psychological distress.16 additionally, several other studies that have assessed depression among skin cancer patients, both in us and non-us samples, have reported a 15%-23.5% prevalence rate of comorbid depression.24–26 the study results bring to attention the incremental impact of depression on hrqol among skin cancer survivors. in comparison with those without depression, skin cancer survivors with depression were worse off on all aspects of hrqol general health status, physical hrqol, mental hrqol, and activity limitations. in this study, we found that depression had the greatest impact on mental hrqol of skin cancer survivors. for adult skin cancer survivors with depression, the odds of poor mental hrqol, were ~6 times that for those without depression. this finding was endorsed by previous studies. a study by trask et al., in a midwestern, multicenter melanoma clinic reported around 33% of the patients to be afflicted with moderate or high psychological distress and increased distress was seen to be correlated with inferior qol and impaired functioning. trask et al. hypothesized that the inversely proportional relationship of distress and qol is due to the coping technique employed by individuals.16 although limited evidence is available regarding the impact of depression on mental hrqol among skin cancer patients, this relationship has been explored among patients with other cancer types. a cross-sectional study of baseline data, from a randomized control trial of adult cancer patients, assessing the relationship between depression and hrqol found that depression impacted all domains of hrqol, including mental health, vitality, perceived disability, overall quality of life, and general health perceptions.18 another study, that examined the association of comorbid depression with hrqol among german cancer patients, found comorbid depression to be a predictor of mental hrqol, controlling for the patient’s physicianassessed performance status.27 given the severe impact of depression on mental hrqol of skin cancer survivors, psychological health profile evaluation can be considered during routine clinic visits to enable better management for such patients. this study also found depression to be strongly associated with poor physical hrqol and activity limitations. adult skin cancer survivors with depression had around 2 times the odds of poor physical hrqol, and 2.5 times the odds of activity limitations as compared to those without depression. trask et al., in a study of melanoma patients, found depression to be significantly associated with worse physical functioning.16 however, this study only assessed people who were currently undergoing treatment for melanoma. our study, on the other hand, assessed the impact of depression on all skin cancer survivors, not just those who are currently undergoing treatment. moreover, the trask et al. study comprised of only melanoma patients. our study sample skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 391 included any skin cancer (melanoma or nmsc). the impact of depression on physical health and activity limitations has been previously seen in studies of survivors of other cancers as well. a cross-sectional study of fatigue (also, defined as activity limitation) in survivors of hodgkin’s disease found fatigue to have moderate correlation with depression, and that depression was a significant risk factor for fatigue.28 another study that assessed the relationship between fatigue and psychological distress in a sample of uterine cancer patients found depression to not only be significantly correlated with activity limitations, but also that depression explained almost 50% of the variance in levels of activity limitation.29 a prospective study of head and neck cancer patients, conducted in the us, reported depression to be significantly associated with poor physical qol.30 a registry-based study, conducted in germany, that assessed anxiety and depression in working age cancer survivors found depression to have an inverse relationship with physical health.31 faller et al., in a study of a representative sample of german cancer patients, found depression to be significantly associated with physical hrqol.27 given the significant burden of depression on physical health and activity limitations of skin cancer survivors, assessment of physical health profiles should also be integrated into routine clinical care, in addition to psychological health profile assessment. overall, this study has implications from both clinical and policy maker perspectives. from a clinical point of view, the study adds to the evidence base for considering assessment of physical and psychological health profiles of skin cancer survivors during routine care. from a policy maker perspective, this study puts forth evidence for greater emphasis on integration of depression screening and management in care for skin cancer survivors. even though the latest american society of clinical oncology (asco) guidelines, in 2014, call for periodic depression screening for any adult cancer survivor,32 there is paucity of studies that have looked at its implementation in practice. policy makers should consider greater adoption for integrated models for healthcare, especially for skin cancer survivors, in order to initiate depression management as early as possible, minimizing its impact on the skin cancer survivor’s hrqol. even though there are some intervention programs for people with depression and cancer like “depression care for people with cancer,”33 there is a need for more active surveillance and management of depression targeted towards skin cancer survivors. a study on effectiveness of cognitive behavioral intervention for distress among melanoma patients found a significant improvement in several domains of hrqol, including general health, vitality, and mental health.12 future research should also assess the effectiveness of various treatments for depression on improvement in hrqol among skin cancer survivors. this study had certain limitations. first, due to the cross-sectional nature of the study design, causality cannot be inferred. future research could study temporality by using a longitudinal design. second, brfss data is self-report, which is susceptible to recall bias. also, since there is no clinical validation of disease status, under-reporting or overreporting of depression is a possibility. moreover, there was no indicator of depression severity and treatment in the data. accounting for these variables may help further understand the relationship between hrqol and comorbid depression. in spite of the limitations discussed above, we believe that assessment of the relationship between depression and hrqol using a nationally representative skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 392 data set is an important addition to the pool of scientific literature on depression and skin cancer. to the best of our knowledge, there are no prior studies that have assessed the relationship between depression and hrqol in a nationally representative sample of skin cancer survivors. the results highlight the strong association between presence of depression and poor hrqol. the study accentuates the even sharper impact of depression on mental hrqol among skin cancer survivors. it serves as an evidence for the need for more active surveillance and management of depression among skin cancer survivors, which in turn has the potential to vastly improve their hrqol. conflict of interest disclosures: none funding: none corresponding author: kaustuv bhattacharya, ms faser hall 136 department of pharmacy administration school of pharmacy p.o. box 1848, university, ms 38677 tel: (662) 801-6564 email: kaustuv.bhattacharya89@gmail.com references: 1. american cancer society. key statistics for basal and squamous cell skin cancers. available at https://www.cancer.org/cancer/basal-andsquamous-cell-skin-cancer/about/keystatistics.html. accessed march 7, 2019 2. american cancer society. key statistics for melanoma skin cancer. available at https://www.cancer.org/cancer/melanoma-skincancer/about/key-statistics.html. accessed march 7, 2019. 3. cornish d, holterhues c, poll-franse vd, v l, coebergh jw, nijsten t. a systematic review of health-related quality of life in cutaneous melanoma. ann oncol. 2009;20(suppl_6):vi51vi58. doi:10.1093/annonc/mdp255 4. cormier jn, ross mi, gershenwald je, et al. prospective assessment of the reliability, validity, and sensitivity to change of the functional assessment of cancer therapy-melanoma questionnaire. cancer. 2008;112(10):2249-2257. doi:10.1002/cncr.23424 5. cormier jn, askew rl. assessment of patientreported outcomes in patients with melanoma. surg oncol clin. 2011;20(1):201-213. doi:10.1016/j.soc.2010.09.002 6. hamel j-f, pe m, coens c, et al. a systematic review examining factors influencing health related quality of life among melanoma cancer survivors. eur j cancer. 2016;69:189-198. doi:10.1016/j.ejca.2016.10.008 7. cohen l, parker pa, sterner j, de moor c. quality of life in patients with malignant melanoma participating in a phase i trial of an autologous tumour-derived vaccine. melanoma res. 2002;12(5):505. 8. rhee js, loberiza fr, matthews ba, neuburg m, smith tl, burzynski m. quality of life assessment in nonmelanoma cervicofacial skin cancer. the laryngoscope. 2003;113(2):215-220. doi:10.1097/00005537-200302000-00004 9. chren m-m. the skindex instruments to measure the effects of skin disease on quality of life. dermatol clin. 2012;30(2):231-236. doi:10.1016/j.det.2011.11.003 10. hawkins dm, jacobsen g, johnson cc, lim hw, eide mj. self-reported quality of life after skin cancer in young adults. j dermatol treat. 2015;26(4):357-360. doi:10.3109/09546634.2014.991671 11. gaulin c, sebaratnam df, fernández-peñas p. quality of life in non-melanoma skin cancer. australas j dermatol. 2015;56(1):70-76. doi:10.1111/ajd.12205 12. trask pc, paterson ag, griffith ka, riba mb, schwartz jl. cognitive-behavioral intervention for distress in patients with melanoma. cancer. 2003;98(4):854-864. doi:10.1002/cncr.11579 conclusion mailto:kaustuv.bhattacharya89@gmail.com skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 393 13. kasparian na, mcloone jk, butow pn. psychological responses and coping strategies among patients with malignant melanoma: a systematic review of the literature. arch dermatol. 2009;145(12):1415-1427. doi:10.1001/archdermatol.2009.308 14. zabora j, brintzenhofeszoc k, curbow b, hooker c, piantadosi s. the prevalence of psychological distress by cancer site. psychooncology. 2001;10(1):19-28. doi:10.1002/10991611(200101/02)10:1<19::aidpon501>3.0.co;2-6 15. kasparian na. psychological stress and melanoma: are we meeting our patients’ psychological needs? clin dermatol. 2013;31(1):41-46. doi:10.1016/j.clindermatol.2011.11.005 16. trask pc, paterson ag, hayasaka s, dunn rl, riba m, johnson t. psychosocial characteristics of individuals with non–stage iv melanoma. j clin oncol. 2001;19(11):2844-2850. doi:10.1200/jco.2001.19.11.2844 17. hoffman ke, mccarthy ep, recklitis cj, ng ak. psychological distress in long-term survivors of adult-onset cancer: results from a national survey. arch intern med. 2009;169(14):12741281. doi:10.1001/archinternmed.2009.179 18. brown lf, kroenke k, theobald de, wu j, tu w. the association of depression and anxiety with health‐related quality of life in cancer patients with depression and/or pain. psycho‐oncology. 2010;19(7):734-741. doi:10.1002/pon.1627 19. kroenke k, theobald d, wu j, loza jk, carpenter js, tu w. the association of depression and pain with health-related quality of life, disability, and health care use in cancer patients. j pain symptom manage. 2010;40(3):327-341. doi:10.1016/j.jpainsymman.2009.12.023 20. reyes-gibby cc, anderson ko, morrow pk, shete s, hassan s. depressive symptoms and health-related quality of life in breast cancer survivors. j womens health. 2011;21(3):311-318. doi:10.1089/jwh.2011.2852 21. centers for disease control and prevention. measuring healthy days: population assessment of health-related quality of life. atlanta, ga.: cdc; 2000. 22. joshi n, khanna r, shah rm. relationship between depression and physical activity, disability, burden, and health-related quality of life among patients with arthritis. popul health manag. 2014;18(2):104-114. doi:10.1089/pop.2014.0062 23. zhao g, okoro ca, li j, white a, dhingra s, li c. current depression among adult cancer survivors: findings from the 2010 behavioral risk factor surveillance system. cancer epidemiol. 2014;38(6):757-764. doi:10.1016/j.canep.2014.10.002 24. gibertini m, reintgen ds, baile wf. psychosocial aspects of melanoma. ann plast surg. 1992;28(1):17-21. 25. linden w, vodermaier a, mackenzie r, greig d. anxiety and depression after cancer diagnosis: prevalence rates by cancer type, gender, and age. j affect disord. 2012;141(2):343-351. doi:10.1016/j.jad.2012.03.025 26. tas f, karabulut s, guveli h, et al. assessment of anxiety and depression status in turkish cutaneous melanoma patients. asian pac j cancer prev apjcp. 2017;18(2):369-373. doi:10.22034/apjcp.2017.18.2.369 27. faller h, brähler e, härter m, et al. performance status and depressive symptoms as predictors of quality of life in cancer patients. a structural equation modeling analysis. psychooncology. 2015;24(11):1456-1462. doi:10.1002/pon.3811 28. loge jh, abrahamsen af, ekeberg ø, kaasa s. fatigue and psychiatric morbidity among hodgkin’s disease survivors. j pain symptom manage. 2000;19(2):91-99. doi:10.1016/s08853924(99)00148-7 29. ahlberg k, ekman t, wallgren a, gastonjohansson f. fatigue, psychological distress, coping and quality of life in patients with uterine cancer. j adv nurs. 2004;45(2):205-213. doi:10.1046/j.1365-2648.2003.02882.x 30. chan jyk, lua ll, starmer hh, sun dq, rosenblatt es, gourin cg. the relationship between depressive symptoms and initial quality of life and function in head and neck cancer. the laryngoscope. 2011;121(6):1212-1218. doi:10.1002/lary.21788 31. inhestern l, beierlein v, bultmann jc, et al. anxiety and depression in working-age cancer skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 394 survivors: a register-based study. bmc cancer. 2017;17(1):347. doi:10.1186/s12885-017-3347-9 32. andersen bl, rowland jh, somerfield mr. screening, assessment, and care of anxiety and depressive symptoms in adults with cancer: an american society of clinical oncology guideline adaptation. j oncol pract. 2015;11(2):133-134. doi:10.1200/jop.2014.002311 33. strong v, waters r, hibberd c, et al. management of depression for people with cancer (smart oncology 1): a randomised trial. the lancet. 2008;372(9632):40-48. doi:10.1016/s01406736(08)60991-5 skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 126 rising derm stars® de novo versus nevus-associated melanomas: differences in associations with prognostic indicators and survival rachel cymerman, md, ms1, yongzhao shao, kun wang, yilong zhang, era c. murzaku, lauren a. penn, iman osman, david polsky 1department of dermatology, new york university, new york, ny background/objectives: although 20%30% of melanomas are histopathologically ‘nevus-associated’, the majority of melanomas arise de novo, i.e. in clinically normal skin with no associated nevus. we examined whether these forms of melanoma differed in their associations with clinical and histopathologic features, and patient survival. methods: we analyzed 2 prospective cohorts from our institution with protocol– driven follow up information (nyu1, n=1048; nyu2, n=1202). we used univariate and multivariate analyses to examine associations between de novo versus nevusassociated melanoma classification and age, anatomic site, tumor thickness, tumor ulceration, mitotic index, histological subtype, clinical stage, and survival. we tested the associations identified in nyu1 using nyu2 as a replication cohort. results: in nyu1, de novo melanomas were associated with tumor thickness > 1.0mm (p<0.0001), ulceration (p=.024), nodular subtype (p=.009), stage > 1 (p<0.0001), older age (p<0.0001), and shorter overall survival (p=.0007). in nyu2, de novo melanoma was again significantly associated with tumor thickness > 1.0mm (p<0.0001), ulceration (p<0.0001), nodular subtype (p<0.0001), stage > 1 (p<0.0001), older age (p<0.0001), and shorter overall survival (p<0.0001). in multivariate analysis, de novo classification was an independent, poor prognostic indicator. male patients had a statistically significantly worse survival than female patients if their melanoma was de novo (nyu1, p<0.0001; nyu2, p=0.0004); unexpectedly, there was no gender difference in survival among patients with nevus-associated tumors. conclusion: these data suggest that de novo melanomas are more aggressive than nevus-associated melanomas. this classification scheme may also provide a useful framework for investigations into gender differences in melanoma outcomes. recognizing these trends may have implications for screening. skin july 2021 1214 proof returned skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 418 brief article a case of cutaneous sarcoidosis with direct osseous involvement simran chadha, bs1, jennifer l. shastry, bs2, erin n. mccomb, md3, christina clarke, md2 1 northwestern university feinberg school of medicine, chicago, il 2 department of dermatology, northwestern university feinberg school of medicine, chicago, il 3 department of radiology, northwestern university feinberg school of medicine, chicago, il sarcoidosis is a multisystem autoinflammatory granulomatous disorder that primarily involves the lungs.1 in approximately 25-30% of cases, cutaneous manifestations are noted, and often correlate with systemic inflammation.2 although skin involvement can manifest variably and may even involve the mucosa, lesions often have a predilection to sites of previous injury, including scars and tattoos.2 here, we present a case of cutaneous sarcoidosis as the first sign of systemic disease, located at the site of a previous injury, with direct underlying osseous involvement. a black male in his 50s presented with a firm, fixed nodule on the forehead at the site of a scar from a childhood injury. the nodule was previously treated with ten days of trimethoprim-sulfamethoxazole for a presumed diagnosis of skin abscess, but continued to enlarge despite antibiotic therapy. the lesion was asymptomatic and had not drained. physical examination demonstrated a 3 cm firm, fixed subcutaneous nodule without significant epidermal change or warmth on the left forehead (figure 1). review of systems was negative for fevers, chills, cough, shortness of breath, weight loss, dizziness, headaches, vision changes. ultrasound demonstrated a heterogenous soft tissue mass overlying the left frontal bone with internal vascularity and microcalcifications. ct of the head and neck demonstrated a 0.8 x 3.0 x 4.2 cm mass, lymphadenopathy in the right lower neck and mediastinum, and, notably, subtle areas of irregularity involving the underlying bone, abstract sarcoidosis is a granulomatous disorder that presents with cutaneous manifestations in one-third of patients, often as an initial symptom prompting interaction with the healthcare system. here, we report a case of cutaneous sarcoidosis on the forehead with directly underlying erosive osseous disease. the patient was imaged further, uncovering pulmonary involvement. the lesion was treated with topical and intralesional corticosteroids with significant resolution. though there exist a range of classic eruptions associated with sarcoidosis, skin involvement can present variably and should prompt additional imaging, particularly to assess for osseous and pulmonary involvement. topical and intralesional corticosteroids can be effective first-line therapy for cutaneous sarcoidosis. introduction case report skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 419 concerning for osseous erosion secondary to an aggressive neoplasm (figure 2). figure 1. a) 1 cm horizontal scar from childhood b) fixed subcutaneous mass on left forehead a fine needle aspiration was performed, and pathology demonstrated nonspecific rare fibroblasts in a background of debris. thus, an excisional biopsy was performed; histopathologic analysis demonstrated aggregates of epithelioid histiocytes forming multiple non-caseating granulomas in the dermis (figure 3). acid-fast bacilli stains were negative for mycobacteria, and polarizable material was not identified. granulomatous disease became the leading diagnosis and a ct of the chest demonstrated bilateral hilar lymphadenopathy and lung nodules in a perilymphatic distribution. the histopathologic and radiographic findings figure 2. a) contrast enhanced axial ct images in soft tissue and bone b) algorithms show a soft tissue mass in the left forehead (arrowhead) and focal areas of subtle erosion in the adjacent frontal bone (arrows). figure 3. section of left forehead excisional biopsy showed numerous dermal aggregates of epithelioid histiocytes and multinucleated giant cells with fibroplasia and a perivascular lymphohistiocytic infiltrate. (h&e, x10) were consistent with a diagnosis of sarcoidosis. the patient was initially treated with topical mometasone cream while establishing a diagnosis of cutaneous sarcoidosis. the patient was then transitioned to minocycline a b a b skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 420 and hydroxychloroquine, and later methotrexate. the skin nodule was treated with intralesional triamcinolone injection, with significant softening of the mass after the first injection. a total of three rounds of intralesional steroids were administered with marked clinical improvement. the prevalence of sarcoidosis in the united states is 10 to 40 per 100,000 persons, with a higher incidence in african americans and women.3 the classic skin manifestations of sarcoidosis include red-brown to violaceous papules and plaques, generally symmetric in distribution and favoring the nose, periocular, perioral face.4 however, cutaneous sarcoidosis can present variably and is considered an imitator of other skin diseases.4 overarchingly, manifestations are classified as either specific – containing noncaseating granulomas on pathology – or nonspecific – without granulomas on pathology but present in the context of systemic disease.1 this patient notes a specific, albeit atypical, manifestation with direct extension of granulomatous disease to deeper structures. bony involvement of sarcoidosis is reported in 5 to 10% of patients and has been correlated with skin involvement – that is, it is rare to have osseous manifestations without cutaneous manifestations.5 despite this, there is a paucity of case reports documenting direct bony invasion of a cutaneous sarcoidosis lesion.6, 7 to the authors’ knowledge, only one previous case of direct invasion has been reported, involving the nasal bone.7 in both this case and the previous report, overlying skin involvement caused a significant burden of symptoms; however, isolated osseous sarcoidosis is often asymptomatic and incidentally detected on imaging.7, 8 sarcoidosis involving the small bones most commonly affects the hands and feet and, radiographically, has a lace-like, lytic appearance. sarcoidosis of the large bones can be lytic or sclerotic and may present as focal lesions or diffuse marrow infiltration.7, 9, 10 among cutaneous manifestations, lupus pernio may be more associated with bone cysts, though uncommonly through direct extension.1 the diagnosis of cutaneous sarcoidosis requires skin biopsy and histopathological confirmation illustrating non-caseating granulomas composed of epithelioid histiocytes. confirmation of diagnosis should prompt a thorough systemic evaluation including history, physical examination, laboratory work-up (complete blood count, comprehensive metabolic panel, thyroid function tests), and chest radiography.2 additional imaging may be indicated to characterize extrapulmonary involvement, particularly in the presence of correlating clinical symptoms. osseous disease is best characterized with mri or pet/ct and may or may not prompt need for pathologic confirmation of diagnosis.8 topical and intralesional steroids are first line in the treatment of cutaneous sarcoidosis. depending on severity of skin disease and involvement of other organ systems, other treatment modalities include anti-malarials, minocycline, methotrexate, thalidomide, and tnf alpha inhibitors.11 such systemic therapies, with the addition of oral or intravenous glucocorticoids, also effectively treat symptoms associated with osseous sarcoidosis. however, in the absence of symptoms, there are no clear treatment guidelines for bone involvement.8 finally, discussion conclusion skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 421 while certain cutaneous morphologies of sarcoidosis portend a worse prognosis – for example, lupus pernio – osseous disease has a more benign natural history.2, 12 previous studies have linked osseous sarcoidosis to favorable outcomes and the vast majority of cases remain stable or improved with treatment.12 thus, this case demonstrates an unusual presentation of cutaneous sarcoidosis in which imaging suggested direct osseous involvement, with excellent response to intralesional steroid injection. conflict of interest disclosures: none funding: none corresponding author: simran chadha feinberg school of medicine northwestern university 402 e superior st chicago, il 60611 phone: 312-695-8106 email: simran.chadha@northwestern.edu references: 1. deepak ar, dellaripa pf. extrapulmonary manifestations of sarcoidosis. rheum dis clin north am. 2013;39(2a):277-297. doi: 10.1016/j.rdc.2013.02.007. 2. wanat ka, rosenbach m. cutaneous sarcoidosis. clin chest med. 2015; 36(4):685-702. doi: 10.1016/j.ccm.2015.08.010. 3. haimovic a, sanchez m, judson ma, prystowsky s. sarcoidosis: a comprehensive review and update for the dermatologist: part 1. cutaneous disease. j am acad dermatol. 2012;66(5):699.e118; quiz 717-8. doi: 10.1016/j.jaad/2011.11.965. 4. judson ma. the clinical features of sarcoidosis: a comprehensive review. clin rev allergy immunol. 2015;49(1):63-78. doi: 10.1007/s12016014-8450-y. 5. heffner dk. explaining sarcoidosis of bone. ann diagn pathol. 2007; 11(6):464-469. doi:10.1016/j.anndiagpath.2007.08.005. 6. jansen tl, geusens pp. sarcoidosis: joint, muscle, and bone involvement. eur respir j monogr. 2005;10:210-219. doi: 10.1183/1025448x.00032013. 7. korkmaz m, uslu s, korkmaz h, centikol y. a rare presentation of sarcoidosis with nasal bone involvement. allergy rhinol (providence). 2016;7(1):e45-e49. doi: 10.2500/ar.2016.7.0152. 8. hassine b, rein c, comarmond c, et al. osseous sarcoidosis: a multicenter retrospective casecontrol study of 48 patients. joint bone spine. 2019; 86(6):789-793. doi: 10.1016/j.jbspin.2019.07.009. 9. maduriera p, pimenta s, cardoso h, cunha rg, costa l. sarcoidosis: an unusual presentation. reumatol clin. 2017;13(4):227-229. doi: 10.1016/j.reuma.2016.03.008. 10. yachoui r, parker bj, nguyen tt. bone and bone marrow involvement in sarcoidosis. rheumatol int. 2015; 35(11):1917-1924. doi: 10.1007/s00296015-3341-y. 11. doherty cb, rosen t. evidence-based therapy for cutaneous sarcoidosis. drugs. 2008;68(10):1361-1383. doi: 10.2165/00003495200868100-00003. 12. miller er, fanta ch, mcsparron ji, et al. musculoskeletal and pulmonary outcomes of sarcoidosis after initial presentation of osseous involvement. sarcoidosis vasc diffuse lung dis. 2019; 36(1):60-73. doi: 10.36141/svdld.v36i1.7326. skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 289 brief article a case of metastatic malignant melanoma simulating granuloma annulare haley d. heibel, md,1 parneet dhaliwal, do,2 etan marks, do,3 clay j. cockerell, md, mba1,4 1cockerell dermatopathology, dallas, tx 2department of pathology, baylor university medical center, dallas, tx 3advanced dermatology and cosmetic surgery, delray beach, fl 4departments of dermatology and pathology, ut southwestern medical center, dallas, tx malignant melanoma is a complex malignancy that can present with a wide range of histological patterns, including mimicking other malignant tumors and benign entities, such as interstitial granulomatous processes.1,2 similarly, metastatic melanoma has a wide variety of clinical presentations that may not be visible to the clinician and may not seem suspicious for melanoma.1 all of these factors contribute to the challenges with making an accurate diagnosis of metastatic melanoma. beyond the classical forms of melanoma (lentigo maligna, superficial spreading, nodular, acral-lentiginous, and mucosal), there are other unusual variants.2 these variants may be amelanotic and mimic other benign and malignant processes both clinically and histopathologically, often require additional testing for diagnosis, and represent a diagnostic challenge.3 in addition, granulomatous reactions associated with melanoma, cutaneous granulomatous reactions following the initiation of treatment for metastatic melanoma, and metastatic melanoma mimicking an interstitial granulomatous reaction have been reported.1,4-8 here, we present a case of a patient with a history of melanoma and locally metastatic melanoma, who developed a right forearm nodule near the previous melanoma excision site. histologically, the lesion presented as abstract malignant melanoma and particularly metastatic melanoma represent a diagnostic challenge due to the wide variety of histologic patterns, resemblance to benign entities, and extensive range of clinical presentations. a high index of suspicion for melanoma is important for accurate diagnosis, especially when there is a previous history of malignancy. here, we present a patient with a history of melanoma and locally metastatic melanoma, who subsequently developed a nodule on his right forearm near the site of his previous melanoma excision. histologically, the melanoma appeared as granuloma annulare (ga) with benign cytologic features, but was identified as metastatic melanoma using sox-10 immunohistochemical staining. other malignancies, including lymphomas, leukemias, sarcomas, and cutaneous metastases of internal malignancies, have mimicked ga and interstitial granulomatous processes. therefore, further immunohistochemical staining should be performed to assess for metastatic disease in the setting of a histological pattern that resembles a benign granulomatous process in a patient with a history of malignancy, including malignant melanoma. introduction skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 290 granuloma annulare (ga) with benign cytologic features, but was identified as metastatic melanoma through positive immunohistochemical staining for sox-10. an 89-year-old male with a history of melanoma presented with a flesh-colored nodule on the right dorsal forearm adjacent to the site of the previous melanoma excision (figure 1). his primary melanoma had been diagnosed 14 years previously on his right forearm with an initial depth of 1.4 mm (pathologic stage: pt2a). he additionally had 3 locally metastatic melanomas near the surgical excision site of the original melanoma occurring 11, 5, and 1 year(s) prior to presentation. sentinel lymph node biopsies were negative for the primary melanoma and the first locally metastatic melanoma, but there was no sentinel lymph node biopsy done for the second locally metastatic melanoma. there was no evidence of other metastases at the time of evaluation of the first and second locally metastatic melanomas by pet/ct imaging of the head, neck, chest, abdomen, and pelvis. the patient then underwent excision of these lesions with negative margins. however, the second metastatic lesion required re-excision for a close margin of 1 mm. when the third locally metastatic melanoma developed on his right forearm, he again underwent excision of this lesion. at this time, a pet/ct scan demonstrated an enlarged 1.6 cm right sided pelvic lymph node, although ct-guided fna of the right pelvic lymph node was nonspecific. a repeat core needle biopsy of the lymph node 2 months later showed no evidence of malignancy. however, another pet-ct scan 6 months later showed a metabolically figure 1. clinical presentation: a flesh-colored nodule on the right dorsal forearm adjacent to the site of previous melanoma excision active right adrenal mass and right external iliac lymph node. ct guided biopsy of the right adrenal mass was consistent with metastatic melanoma. genetic testing was negative for braf mutation. he was initiated on nivolumab (240 mg every 2 weeks) 10 months subsequent to the diagnosis of this metastatic melanoma and 2 months prior to the development of this most recent skin lesion. initial histopathologic examination of the most recent skin lesion (fourth lesion appearing at the site of the primary melanoma excision) demonstrated discrete areas of what appeared to be palisading histiocytes surrounding collections of mucin and perivascular lymphocytes with benign appearing cytologic features consistent with probable ga (figure 2). given the patient’s history of melanoma, immunohistochemical staining was performed to exclude a melanocytic process and revealed cells strongly positive for sox-10 (figure 3). however, only scattered cells were highlighted with cd68. these features were case presentation skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 291 consistent with metastatic melanoma simulating ga. figure 2. histologic images showing an interstitial infiltrate resembling granuloma annulare with cells wrapping around collagen bundles. the cells have a benign appearance without any obvious mitotic figures or significant pleomorphism. figure 3. sox-10 immunohistochemical staining revealing the cells are melanocytes. the patient has continued nivolumab therapy (240 mg every 2 weeks) to the present time. he also completed radiation therapy for his right adrenal lesion. he has been followed with serial pet/ct scans, and a slight increase in the size of the right adrenal lesion was observed 14 months after its initial identification, but no other evidence of metastases or disease progression has been identified. cutaneous manifestations of lymphomas (including mycosis fungoides), leukemias, and sarcomas have resembled ga both clinically and histologically.1,9,10 hartman et al9 reported 3 cases of cutaneous metastases of internal malignancies (including breast and salivary gland mucoepidermoid carcinomas) that histologically mimicked interstitial granulomatous processes, with one case clinically appearing as ga. the malignant carcinoma cells were organized in an interstitial pattern, although some of the cells did not have significant cellular atypia. parekh et al1 described another patient who presented with a melanoma and subsequently developed cutaneous metastases. wide excision of the scar and metastases demonstrated histologic findings of an amelanotic process separate from the original wound of operation with a differential diagnosis of ga and some other form of an interstitial granulomatous process. the amelanotic, poorly differentiated cells were identified as metastatic melanoma through positive mart-1 immunohistochemical staining. the etiology of a granulomatous process associated with metastatic melanoma is unclear, but theories include a cell-mediated immune response against an antigenic factor derived from tumor cells or that melanoma cells secrete cytokines which attract histiocytes and lead to granuloma formation.7 in the setting of granulomatous reactions occurring during the treatment of melanoma, park et al6 suggested this may represent immune activation against tumor discussion skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 292 cells. reports of ga occurring subsequent to the initiation of immune checkpoint inhibitors have been reported as well.8 our patient had initiated nivolumab 2 months prior to his presentation with this new skin lesion. therefore, the histiocytes admixed with the melanocytes could be related to some form of immune activation and gave the appearance of ga. metastatic melanoma can present with a wide variety of clinical presentations.1 this case illustrates the importance of the provision of accurate and complete medical history by the submitting clinician and communicating this information clearly to the dermatopathologist. this information may affect stains selected by the dermatopathologist and the histopathologic diagnosis, especially when the histopathologic pattern is a granulomatous process in a patient with a history of malignancy. in this case, clinical history of a melanoma was critical for achieving an accurate histopathologic diagnosis because it prompted further staining to assess for a melanocytic process. in the presence of a histological pattern that resembles a benign granulomatous process in a patient with a history of malignancy, including malignant melanoma, further immunohistochemical staining should be performed to assess for metastatic disease.9 abbreviations used: granuloma annulare (ga) acknowledgements: the authors would like to thank andrew ondo, m.d., for providing the clinical information and clinical photo for this manuscript. conflict of interest disclosures: haley d. heibel, parneet dhaliwal, etan marks, and clay j. cockerell declare that they have no conflicts of interests that may be related to the contents of this manuscript. funding: none corresponding author: haley d. heibel, md 2110 research row, suite 100 dallas, tx 75235 phone: 214-530-5200 email: hheibel@dermpath.com references: 1. parekh v, miller cj, elenitsas r, chu ey. cutaneous metastases of melanoma mimicking interstitial granulomatous processes. am j dermatopathol. 2018;40(9):706-707. 2. rongioletti f, smoller br. unusual histological variants of cutaneous malignant melanoma with some clinical and possible prognostic correlations. j cutan pathol. 2005;32(9):589-603. 3. barnhill rl, gupta k. unusual variants of malignant melanoma. clin dermatol. 2009;27(6):564-587. 4. garrido mc, gutierrez c, riveiro-falkenbach e, ortiz p, rodriguez-peralto jl. braf inhibitor-induced antitumoral granulomatous dermatitis eruption in advanced melanoma. am j dermatopathol. 2015;37(10):795-798. 5. korman am, nisar ms, somach sc. subclinical granulomas in benign skin lesions heralding the onset of braf and mek inhibitor–associated granulomatous dermatitis in a patient with metastatic melanoma. jaad case reports. 2018;4(7):722-724. 6. park jj, hawryluk eb, tahan sr, flaherty k, kim cc. cutaneous granulomatous eruption and successful response to potent topical steroids in patients undergoing targeted braf inhibitor treatment for metastatic melanoma. jama dermatol. 2014;150(3):307-311. 7. robert c, schoenlaub p, avril m, et al. malignant melanoma and granulomatosis. br j dermatol. 1997;137(5):787-792. 8. wu j, kwong by, martires kj, et al. granuloma annulare associated with immune checkpoint inhibitors. j eur acad dermatol venereol. 2018;32(4):e124-e126. 9. hartman ri, chu ey, acker sm, james wd, elenitsas r, kovarik cl. cutaneous metastases from visceral malignancies mimicking interstitial granulomatous processes: a report of 3 cases. am j dermatopathol. 2013;35(5):601-605. 10. jouary t, beylot‐barry m, vergier b, paroissien j, doutre ms, beylot c. mycosis fungoides mimicking granuloma annulare. br j dermatol. 2002;146(6):11021103. conclusion mailto:hheibel@dermpath.com deucravacitinib, an oral, selective tyrosine kinase 2 (tyk2) inhibitor, versus placebo and apremilast in moderate to severe plaque psoriasis: efficacy analysis by baseline disease characteristics from the phase 3 poetyk pso-1 and pso-2 trials joseph f merola,1 howard sofen,2 diamant thaçi,3 carle paul,4 shinichi imafuku,5 subhashis banerjee,6 elizabeth colston,6 jonghyeon kim,6 john throup,6 april w armstrong7 1brigham and women’s hospital, brigham dermatology associates, harvard medical school, boston, ma, usa; 2ucla school of medicine, los angeles, ca, usa; 3university of lübeck, lübeck, germany; 4larrey university hospital, paul sabatier university, toulouse, france; 5fukuoka university hospital, fukuoka, japan; 6bristol myers squibb, princeton, nj, usa; 7university of southern california, los angeles, ca, usa introduction • deucravacitinib — novel, oral, selective tyrosine kinase 2 (tyk2) inhibitor with a unique mechanism of action distinct from janus kinase (jak) 1/2/3 inhibitors (figure 1)1 • binds to the tyk2 regulatory domain with high selectivity and inhibits tyk2 via an allosteric mechanism1 — ≥100-fold greater selectivity for tyk2 vs jak 1/3 and ≥2000-fold greater selectivity for tyk2 vs jak 2 in cells1,2 • inhibits tyk2-mediated signaling of cytokines involved in psoriasis pathogenesis (eg, interleukin [il]-23, il-12, and type i interferons)1 figure 1. mechanism of action of deucravacitinib deucravacitinib (allosteric inhibitor) regulatory domain catalytic domain atp-binding active site (other kinase inhibitors) tyk2 atp, adenosine triphosphate; tyk2, tyrosine kinase 2. • deucravacitinib has demonstrated good efficacy and tolerability in phase 2 trials in patients with moderate to severe plaque psoriasis3 and with active psoriatic arthritis4 • in 2 pivotal phase 3 trials in patients with moderate to severe plaque psoriasis, poetyk pso-1 (nct03624127) and poetyk pso-2 (nct03611751), a significantly greater proportion of patients achieved ≥75% reduction from baseline in psoriasis area and severity index (pasi 75) score and a static physician’s global assessment (spga) score of 0 or 1 (0/1) at week 16 with deucravacitinib compared with placebo or apremilast5 objective • the present analyses were performed to evaluate the efficacy of deucravacitinib at week 16 by prespecified baseline disease characteristics in the phase 3 poetyk pso-1 and pso-2 trials methods key design elements • the poetyk pso-1 and pso-2 study designs are shown in figure 2 • key eligibility criteria — adults with moderate to severe plaque psoriasis — pasi ≥12, spga ≥3, body surface area (bsa) ≥10% — stratified by geographic region, body weight, and prior biologic use • coprimary endpoints were the proportion of patients who achieved pasi 75 and spga 0/1 responses vs placebo at week 16 • data from subgroups with the following predefined baseline disease characteristics in pso-1 and pso-2 were pooled and analyzed for the coprimary endpoints vs placebo and vs apremilast at week 16: — moderate vs severe disease • pasi score: 12−20 vs ≥20 • spga score: 3 vs 4 • bsa involvement: 10%−20% vs >20% — disease duration: <10 y vs ≥10 y — age at disease onset subgroups: <18 y, 18−39 y, ≥40 y • additional subgroups for age at disease onset (<18 y, 18−39 y, 40−55 y, >55 y) and disease duration (1−5 y, 5−15 y, 15−20 y, >20 y) were analyzed post hoc • differences between treatment groups were calculated using a stratified cochran-mantel-haenszel test • missing data were imputed with nonresponder imputation this poster may not be reproduced without written permission from the authors.email for joseph f merola, md: jfmerola@bwh.havard.edu figure 2. study designs poetyk pso-1 (n=666) poetyk pso-2 (n=1020) deucravacitinib 6 mg qdplacebo (n=166) deucravacitinib 6 mg qd<pasi 50 apremilast 30 mg bidpasi 50 titrate*1 :2 :1 r an d om iz at io n weeks 16 24 520 deucravacitinib 6 mg qdplacebo (n=255) deucravacitinib 6 mg qd (n=511) deucravacitinib 6 mg qd<pasi 75 deucravacitinib 6 mg qd<pasi 75 deucravacitinib 6 mg qd deucravacitinib 6 mg qd placebob pasi 75 apremilast 30 mg bida (n=254) pasi 751 :2 :1 r an d om iz at io n weeks 16 24 520 1:1 deucravacitinib 6 mg qdplacebob deucravacitinib 6 mg qd (n=332) primary endpoint primary endpoint apremilast 30 mg bida (n=168) aapremilast was titrated from 10 mg qd to 30 mg bid over the first 5 days of dosing. bupon relapse (≥50% loss of week 24 pasi percentage improvement from baseline), patients were to be switched to deucravacitinib 6 mg qd. bid, twice daily; pasi 50, ≥50% reduction from baseline in psoriasis area and severity index; pasi 75, ≥75% reduction from baseline in pasi; qd, once daily. results baseline patient demographics and disease characteristics • baseline patient demographics and disease characteristics were largely similar across treatment groups in pooled data from the 2 trials (table 1) table 1. baseline patient demographics and disease characteristics pooled poetyk pso-1 and pso-2 placebo (n=421) deucravacitinib (n=843) apremilast (n=422) total (n=1686) age, y, mean (sd) 47.5 (13.7) 46.5 (13.5) 45.7 (12.8) 46.6 (13.4) weight, kg, mean (sd) 90.6 (21.1) 90.6 (21.9) 91.1 (22.0) 90.7 (21.7) female, n (%) 127 (30.2) 277 (32.9) 155 (36.7) 559 (33.2) race, n (%) white 360 (85.5) 741 (87.9) 368 (87.2) 1469 (87.1) asian 42 (10.0) 83 (9.8) 40 (9.5) 165 (9.8) other 19 (4.5) 19 (2.3) 14 (3.3) 52 (3.1) age at disease onset, y, mean (sd) 29.6 (15.2)a 28.8 (14.9) 28.1 (14.7) 28.8 (14.9) <18 y, n (%) 102 (24.2) 208 (24.7) 112 (26.5) 422 (25.0) 18−39 y, n (%) 205 (48.7) 438 (52.0) 215 (50.9) 858 (50.9) ≥40 y, n (%) 113 (26.8) 197 (23.4) 95 (22.5) 405 (24.0) disease duration, y, mean (sd) 18.9 (12.9)a 18.6 (12.7) 18.5 (12.1) 18.6 (12.6) <10 y, n (%) 119 (28.3) 261 (31.0) 112 (26.5) 492 (29.2) ≥10 y, n (%) 301 (71.5) 582 (69.0) 310 (73.5) 1193 (70.8) prior systemic treatment use, n (%) biologic 146 (34.7) 295 (35.0) 145 (34.4) 586 (34.8) no prior systemic therapy 173 (41.1) 369 (43.8) 173 (41.0) 715 (42.4) spga, n (%) 3 = moderate 345 (81.9) 665 (78.9) 335 (79.4) 1345 (79.8) 4 = severe 75 (17.8) 178 (21.1) 87 (20.6) 340 (20.2) pasi, mean (sd) (overall) 20.9 (8.6) 21.1 (8.0) 21.6 (8.6) 21.2 (8.3) pasi 12−20, n (%) 254 (60.3) 475 (56.3) 241 (57.1) 970 (57.5) pasi >20, n (%) 167 (39.7) 368 (43.7) 181 (42.9) 716 (42.5) bsa, mean (sd) (overall) 25.3 (16.1) 26.4 (15.8) 27.6 (16.4) 26.4 (16.0) bsa 10%−20%, n (%) 226 (53.7) 421 (49.9) 200 (47.4) 847 (50.2) bsa >20%, n (%) 195 (46.3) 422 (50.1) 222 (52.6) 839 (49.8) aage at disease onset and disease duration were not reported for 1 patient in the placebo arm of pso-2. bsa, body surface area; pasi, psoriasis area and severity index; spga, static physician’s global assessment. efficacy • in the overall populations, significantly greater proportions of patients receiving deucravacitinib vs placebo and vs apremilast achieved pasi 75 and spga 0/1 responses at week 16 in each study (figure 3)5 figure 3. pasi 75 and spga 0/1 responses at week 16 for pso-1 and pso-2 58.4 53.0 12.7 9.4 35.1 39.8 0 10 20 30 40 50 60 70 80 90 100 pso−1 pso−2 p a si 7 5 r e sp on se , % pasi 75 53.6 49.5 7.2 8.6 32.1 33.9 0 10 20 30 40 50 60 70 80 90 100 pso−1 pso−2 sp g a 0 /1 r e sp o n se , % spga 0/1 deucravacitinib placebo apremilast pasi 75, ≥75% reduction from baseline in psoriasis area and severity index; spga 0/1, static physician’s global assessment score of 0 or 1. • pooled data from pso-1 and pso-2 demonstrated a consistent and favorable treatment benefit by pasi 75 and spga 0/1 responses for deucravacitinib compared with placebo and apremilast in all prespecified baseline disease subgroups at week 16: — disease severity by pasi, spga, and bsa — disease duration — age of disease onset (figure 4 and figure 5) figure 4. pasi 75 response at week 16: pso-1 and pso-2 pooled analysis − efficacy of deucravacitinib vs placebo and apremilast in prespecified subgroups deucravacitinib placebo apremilast 0 10 20 30 40 50 60 difference vs placebo (95% ci) 0 10 20 30 40 50 60 difference vs apremilast (95% ci) baseline pasi ≤20 baseline pasi >20 baseline spga score 3 (moderate) baseline spga score 4 (severe) baseline bsa involvement 10%−20% baseline bsa involvement >20% duration of disease <10 y duration of disease ≥10 y age at disease onset <18 y age at disease onset 18−39 y age at disease onset ≥40 y difference (95% ci) 40.8 (34.9−46.8) 49.1 (42.4−55.8) 43.4 (38.3−48.5) 49.9 (40.7−59.0) 39.5 (33.0−46.0) 49.6 (43.6−55.6) 46.5 (38.5−54.5) 43.5 (38.2−48.9) 45.4 (36.2−54.6) 43.1 (36.9−49.3) 46.8 (37.9−55.7) difference (95% ci) patients, n placebo deucravacitinib apremilast 15.7 (8.1−23.2) 254 475 241 19.0 (10.2−27.7) 167 368 181 16.2 (9.7−22.7) 345 665 335 20.0 (7.6−32.4) 75 178 87 16.6 (8.4−24.8) 226 421 200 17.7 (9.7−25.7) 195 422 222 19.9 (9.1−30.7) 119 261 112 16.1 (9.3−22.9) 301 582 310 16.1 (4.8−27.4) 102 208 112 19.8 (12.0−27.7) 205 438 215 13.2 (1.0−25.3) 113 197 95 deucravacitinib vs placebo deucravacitinib vs apremilast missing data were imputed with nonresponder imputation. bsa, body surface area; pasi 75, ≥75% reduction from baseline in psoriasis area and severity index; spga, static physician’s global assessment. figure 5. spga 0/1 response at week 16: pso-1 and pso-2 pooled analysis − efficacy of deucravacitinib vs placebo and apremilast in prespecified subgroups patients, n 0 10 20 30 40 50 60 difference vs apremilast (95% ci) 0 10 20 30 40 50 60 difference vs placebo (95% ci) baseline pasi ≤20 baseline pasi >20 baseline spga score 3 (moderate) baseline spga score 4 (severe) baseline bsa involvement 10%−20% baseline bsa involvement >20% duration of disease <10 y duration of disease ≥10 y age at disease onset <18 y age at disease onset 18−39 y age at disease onset ≥40 y difference (95% ci) 40.9 (35.0−46.7) 46.0 (40.0−52.1) 42.1 (37.3−47.0) 48.1 (39.9−56.3) 39.8 (33.4−46.2) 46.7 (41.2−52.1) 45.6 (37.9−53.2) 41.8 (36.7−47.0) 40.2 (31.1−49.3) 44.4 (38.5−50.2) 43.4 (34.8−52.0) difference (95% ci) placebo deucravacitinib apremilast 17.9 (10.5−25.4) 254 475 241 17.7 (9.2−26.3) 167 368 181 17.1 (10.7−23.4) 345 665 335 20.3 (8.2−32.3) 75 178 87 17.7 (9.6−25.9) 226 421 200 17.8 (10.0−25.6) 195 422 222 20.6 (10.1−31.1) 119 261 112 16.5 (9.9−23.2) 301 582 310 17.0 (5.9−28.1) 102 208 112 20.0 (12.3−27.8) 205 438 215 14.2 (2.2−26.2) 113 197 95 deucravacitinib vs placebo deucravacitinib vs apremilast missing data were imputed with nonresponder imputation. bsa, body surface area; pasi, psoriasis area and severity index; spga 0/1, static physician’s global assessment score of 0 or 1. • analysis of pooled data from pso-1 and pso-2 demonstrated favorable efficacy for deucravacitinib against placebo and apremilast across most post hoc subgroups with additional strata (figure 6 and figure 7) figure 6. pasi 75 response at week 16: pso-1 and pso-2 pooled analysis − efficacy of deucravacitinib vs placebo and apremilast in post hoc subgroups 0 10 20 30 40 50 60 difference vs placebo (95% ci) age at disease onset >55 y age at disease onset 40−55 y age at disease onset 18−39 y age at disease onset <18 y duration of disease ≥20 y duration of disease 15−<20 y duration of disease 5−<15 y duration of disease 1−<5 y difference (95% ci) 46.7 (29.8−63.7) 47.3 (36.9−57.7) 43.1 (36.9−49.3) 45.4 (36.2−54.6) 39.0 (31.7−46.4) 49.4 (38.2−60.5) 48.7 (41.5−55.9) 42.9 (28.3−57.5) patients, n placebo deucravacitinib apremilast 25 55 25 88 142 70 205 438 215 102 208 112 167 327 167 64 125 62 139 293 146 difference (95% ci) −2.6 (−26.9 to 21.8) 20.2 (6.1−34.2) 19.8 (12.0−27.7) 16.1 (4.8−27.4) 11.6 (2.4−20.8) 18.1 (3.1−33.1) 22.9 (13.3−32.5) 19.1 (1.2−37.0) 48 94 42 deucravacitinib vs placebo deucravacitinib vs apremilast -35 -25 -15 -5 5 15 25 35 difference vs apremilast (95% ci) missing data were imputed with nonresponder imputation. pasi 75, ≥75% reduction from baseline in psoriasis area and severity index. figure 7. spga 0/1 response at week 16: pso-1 and pso-2 pooled analysis − efficacy of deucravacitinib vs placebo and apremilast in post hoc subgroups 0 10 20 30 40 50 60 difference vs placebo (95% ci) difference (95% ci) age at disease onset >55 y 46.7 (31.2−62.1) age at disease onset 40−55 y 42.5 (32.3−52.6) age at disease onset 18−39 y 44.4 (38.5−50.2) age at disease onset <18 y 40.2 (31.1−49.3) duration of disease ≥20 y 37.8 (30.7−44.9) duration of disease 15−<20 y 47.4 (36.7−58.1) duration of disease 5−<15 y 45.7 (38.8−52.7) duration of disease 1−<5 y 45.9 (32.7−59.1) -35 -25 -15 -5 5 15 25 35 difference vs apremilast (95% ci) difference (95% ci) patients, n placebo deucravacitinib apremilast −4.2 (−28.9 to 20.6) 25 55 25 20.4 (6.9−34) 88 142 70 20.0 (12.3−27.8) 205 438 215 17.0 (5.9−28.1) 102 208 112 12.6 (3.6−21.7) 167 327 167 18.3 (3.5−33.1) 64 125 62 23.3 (14.0−32.6) 139 293 146 23.0 (5.6−40.3) 48 94 42 deucravacitinib vs placebo deucravacitinib vs apremilast missing data were imputed with nonresponder imputation. spga 0/1, static physician’s global assessment score of 0 or 1. conclusions • patients treated with deucravacitinib had pasi 75 and spga 0/1 responses that were superior to placebo and apremilast across nearly all prespecified and post hoc baseline disease parameters, including measures of baseline disease severity, duration of psoriasis, and age at disease onset • taken together with the primary results from the phase 3 poetyk trials,5 these findings suggest that deucravacitinib has the potential to become a treatment of choice and new standard of care for patients with moderate to severe plaque psoriasis references 1. burke jr et al. sci transl med 2019;11:1-16. 2. wrobleski st et al. j med chem 2019;62:8973-8995. 3. papp k et al. n engl j med 2018;349:1313-1321. 4. mease pj et al. presented at the annual scientific meeting of the american college of rheumatology; november 5-9, 2020. 5. armstrong a et al. presented at the annual meeting of the american academy of dermatology; april 23-25, 2021. acknowledgments • these clinical trials were sponsored by bristol myers squibb. professional medical writing from lisa feder, phd, and editorial assistance were provided by peloton advantage, llc, an open health company, parsippany, nj, usa, and were funded by bristol myers squibb. relationships and activities • jfm: consultant and/or investigator: amgen, abbvie, biogen, bristol myers squibb, dermavant, eli lilly, janssen, leo pharma, novartis, pfizer, regeneron, sanofi, sun pharma, and ucb • hs: clinical investigator: abbvie, amgen, boehringer ingelheim, bristol myers squibb, eli lilly, janssen, leo pharma, novartis, and sun pharma • dt: advisory board, principal investigator, and lecture fees: abbvie, almirall, amgen, biogen idec, boehringer ingelheim, bristol myers squibb, celgene, ds pharma, eli lilly, galapagos, galderma, janssen-cilag, leo pharma, novartis, pfizer, regeneron, roche-posay, samsung, sandoz-hexal, sanofi, and ucb • cp: grant support and consultant fees: abbvie, almirall, amgen, bristol myers squibb, boehringer ingelheim, celgene, eli lilly, janssen, leo pharma, merck, mylan, novartis, pfizer, pierre fabre, sanofi, and ucb • si: grants and personal fees: abbvie, eisai, janssen, kyowa hakko kirin, leo pharma, maruho, sun pharma, taiho yakuhin, tanabe mitsubishi, torii pharmaceutical, and yakuhin; personal fees: amgen, bristol myers squibb, daiichi sankyo, eli lilly, novartis, and ucb • sb, ec, jk, and jt: employees and shareholders: bristol myers squibb • awa: grants and personal fees: abbvie, bristol myers squibb, eli lilly, janssen, leo pharma, and novartis; personal fees: boehringer ingelheim/parexel, celgene, dermavant, genentech, glaxosmithkline, menlo therapeutics, merck, modernizing medicine, ortho dermatologics, pfizer, regeneron, sanofi genzyme, science 37, sun pharma, and valeant; grant support: dermira, kyowa hakko kirin, and ucb, outside the submitted work presented at the fall clinical dermatology conference®; october 21−24, 2021; las vegas, nv, and virtual this is an encore of the 2021 eadv 30th congress poster conclusions 1 the phase 4 sk-fan study is designed to assess patient satisfaction with hp40 treatment for sks assessing patient satisfaction with hydrogen peroxide topical solution, 40% (w/w) treatment of seborrheic keratoses on the face, neck, and décolletage: objectives and design of the phase 4, open-label sk-fan study janet dubois, md,1 kimberly grande, md, faad,2 judith schnyder, mba,3 stuart d. shanler, md, faad, facms3 1dermresearch, inc., austin, tx; 2the skin wellness center, knoxville, tn; 3aclaris therapeutics, inc., wayne, pa presented at winter clinical dermatology conference, january 18–23, 2019, koloa, hawaii table 2. key inclusion and exclusion criteria of the sk-fan study (cont’d) key exclusion criteria z clinically atypical and/or rapidly growing sk z presence of multiple eruptive sks (sign of lesser-trélat) z current systemic malignancy z previous treatment with hp40 z used previous/current therapies that could interfere with the study treatment or the assessments: — laser, light, or other energy-based therapy (eg, intense pulsed light, photodynamic therapy) within 30 days of first study treatment — imiquimod, 5-fluorouracil, or ingenol mebutate within 60 days of first study treatment — retinoids within 28 days of first study treatment — microdermabrasion or superficial chemical peels within 14 days of first study treatment z currently or recently had on, or in proximity to, any target or nontarget sk: — cutaneous malignancy within 180 days of first study treatment — current sunburn — current pre-malignancy (eg, actinic keratosis) — body art — excessive tan (use of self-tanning lotions/sprays is prohibited) z any current skin disease (eg, psoriasis, atopic dermatitis, eczema, sun damage) or condition (eg, sunburn, excessive hair, open wounds) that might put the subject at undue risk by study participation or interfere with the study conduct or evaluations sk, seborrheic keratosis; sk-fan, seborrheic keratoses of the face, neck and décolletage. investigational product and treatments z hp40 is supplied as a single-use applicator to be applied topically to an sk lesion by a medical professional z hp40 is applied to 3 target sks and up to 4 nontarget sks during visit 2 (study day 1) z during visit 5 (day 15) and visit 7 (day 29), sks that meet the retreatment criterion (pla score of ≥1, indicating lesion not cleared) are retreated z during treatments, hp40 is applied to each target and nontarget sk for approximately 20 seconds, and each target and nontarget sk may be treated up to 4 times with approximately 60 seconds between each application subject satisfaction assessment z participants are asked to assess their level of satisfaction regarding the study medication treatment experience using the ssa z there are 3 versions of the ssa to be administered at specified visits as follows: 8. after treatment with hp40, how bothered are you by the appearance of your treated sks today? • 1 – not bothered at all • 2 – a little bit bothered • 3 – neutral • 4 – somewhat bothered • 5 – extremely bothered 9. since your treatment with hp40, how do you feel about getting your untreated sks treated in the future? • anxious/nervous • concerned/worried • unsure/neutral • hopeful • excited 10. please indicate the level of agreement you have to the following statements: a) since my treatment with hp40, i feel more confident: • strongly agree • disagree • neither disagree or agree • agree • strongly agree b) since my treatment with hp40, i feel more attractive: • strongly agree • disagree • neither disagree or agree • agree • strongly agree c) since my treatment with hp40, i feel less embarrassed: • strongly agree • disagree • neither disagree or agree • agree • strongly agree d) since my treatment with hp40, i feel more comfortable being photographed in pictures: • strongly agree • disagree • neither disagree or agree • agree • strongly agree physician lesion assessment z at visits 1, 2, 3, 4, 5, 7, 10, and 11, the investigator will assess the target and nontarget sk using the pla, a validated tool, and report the integer that best describes the severity of the target or nontarget sk (table 3) z at visit 2, and if applicable, at visits 5 and 7, the investigator completes the pla prior to the study medication treatment table 3. physician lesion assessment scoring grade description 0 clear: no visible sk lesion 1 near clear: a visible sk lesion with a surface appearance different from the surrounding skin (not elevated) 2 thin: a visible sk lesion (thickness ≤1 mm) 3 thick: a visible sk lesion (thickness >1 mm) sk, seborrheic keratosis. outcome measures z primary outcome measure — question #4 of the end-of-study ssa: “on a scale of 1–5, rate your level of satisfaction with the appearance of your skin treated with [hp40].” z secondary outcome measure — question #3 of the end-of-study ssa: “on a scale of 1–5, rate your level of satisfaction of your treatment experience.” z tertiary outcome measures — question #10 and its 4 constructs of confidence, attractiveness, embarrassment, and comfort with being photographed z exploratory outcome measures — predose and postdose ssa ratings z additional analyses — correlations between pla and ssa scores — predictors of treatment satisfaction (ie, participant characteristics) results status z 41 participants have been enrolled at 3 us centers z data analyses are currently ongoing with results expected in early 2019; images of 3 patients treated thus far are shown below patient 1 day 1, pretreatment day 113, end of study patient 2 day 1, pretreatment day 113, end of study patient 3 day 1, pretreatment day 113, end of study references 1. bickers dr, et al. j am acad dermatol. 2006;55:490-500. 2. del rosso jq. j clin aesthet dermatol. 2017;10:16-25. 3. baumann ls, et al. j am acad dermatol. 2018;79:869-77. 4. eskata [package insert]. malvern, pa: aclaris therapeutics, inc.; 2017. acknowledgments this study was funded by aclaris therapeutics, inc. editorial support for this poster was provided by peloton advantage, llc, parsippany, nj, and funded by aclaris therapeutics, inc. disclosures jd has been a principal investigator for and received payment from accuitis, aclaris therapeutics, alexar therapeutics, allergan, atacama therapeutics, athenex, botanix, braintree laboratories, brickell biotech, cellceutix, cutanea life sciences, dermata therapeutics, dermavant sciences, dermira, dfb soria, dusa, endo international, escalier biosciences, foamix, gage development company, galderma usa, glaxosmithkline, glenmark generics, incyte, kiniksa, leo laboratories, medimetriks, moberg, mylan, naked biome, nielsen bioscience, novan, novartis, perrigo, pfizer, promius, santalis, seegpharm, sienna biopharmaceuticals, sol-gel, taro, teva, tolmar, and valeant. kg is an investigator for aclaris therapeutics and has received grants for clinical studies, and has received honoraria as a speaker for aclaris. js and sds are employees of aclaris and may own stock/stock options in that company. email address for questions or comments: duboismd@driresearchsite.com at visit 2 prior to application of hp40: 1. what prior treatments have you used/had performed for sk removal? (select all that apply) • cryotherapy (freezing with liquid nitrogen) • curettage (scraping off tissue) • electrodessication (burning off with electricity) • laser therapy (burning off ) • other (provide name) 2. how bothered are you by the appearance of your face/hairline neck sks? • 1 – not bothered at all • 2 – a little bit bothered • 3 – neutral • 4 – somewhat bothered • 5 – extremely bothered 3. how do you feel about getting your sks treated? (select all that apply) • anxious/nervous • concerned/worried • unsure/neutral • hopeful • excited 4. what prior facial cosmetic treatment(s), excluding cryotherapy for sk removal, have you had for your face in a dermatology clinic or medical spa? (select all that apply) • botulinum toxin injections • hyaluronic acid fillers • hair removal with laser or pulsed light • chemical peel • microdermabrasion • plastic surgery • other (provide name) • none, hp40 will be my first cosmetic treatment for my face at visit 3 approximately 24 hours after the treatment on visit 2, and at visit 6 (if treated at visit 5), approximately 1 week after visit 5 treatment, and at visit 8 (if treated at visit 7), approximately 1 week after visit 7 treatment: 1. during treatment, what was your level of discomfort? • 1 – no discomfort • 2 – mild discomfort • 3 – moderate discomfort • 4 – severe discomfort • 5 – unbearable discomfort 2. one hour after treatment, what was your level of discomfort? • 1 – no discomfort • 2 – mild discomfort • 3 – moderate discomfort • 4 – severe discomfort • 5 – unbearable discomfort 3. one day after treatment, what was your level of discomfort? • 1 – no discomfort • 2 – mild discomfort • 3 – moderate discomfort • 4 – severe discomfort • 5 – unbearable discomfort 4. within 24 hours after treatment, were you comfortable enough with the appearance of your treated sks to go out in public (with or without makeup)? • yes • no 4.a. how soon after your treatment were you comfortable enough with your appearance of your treated sks to go out in public (with or without makeup)? • immediately after treatment • 1–2 hours after treatment • 2–4 hours after treatment • 4–6 hours after treatment • more than 6 hours after treatment at visits 10 and 11 during the visit: 1. please check prior treatments you have personally had for sks (check mark all that apply). • cryotherapy (freezing with −196°c liquid nitrogen) • curettage (scraping off tissue with a sharp instrument) • electrodessication (burning off with high-voltage electricity) • other (please describe) 2. after your experience with hp40, how likely will you pursue future treatment for other sks on your face or body? • 1 – very unlikely • 2 – unlikely • 3 – neither unlikely or likely • 4 – likely • 5 – very likely 3. on a scale of 1–5, rate your level of satisfaction of your treatment experience with 1 being not satisfied at all and 5 being completely satisfied? • 1 – not satisfied at all • 2 – slightly satisfied • 3 – moderately satisfied • 4 – satisfied • 5 – very satisfied 4. on a scale of 1–5, rate your level of satisfaction with the appearance of your skin treated with hp40 with 1 being not satisfied at all and 5 being completely satisfied? • 1 – not satisfied at all • 2 – slightly satisfied • 3 – moderately satisfied • 4 – satisfied • 5 – very satisfied 5. what is the likelihood you will get other sks treated in the future with hp40? • 1 – not likely at all • 2 – slightly likely • 3 – moderately likely • 4 – very likely • 5 – extremely likely 6. what is the likelihood you will recommend hp40 to a friend/relative? • 1 – not likely at all • 2 – slightly likely • 3 – moderately likely • 4 – very likely • 5 – extremely likely 7. for an sk you would like to treat in the future, please rank your preferred treatment method (1 – most preferred; 5 – least preferred). • hp40 (topical application) • cryotherapy (freezing with −196°c liquid nitrogen) • curettage (scraping off tissue with a sharp instrument) • electrodessication (burning off with high-voltage electricity) • other (please describe) synopsis z seborrheic keratoses (sks) are benign cutaneous lesions affecting nearly 84 million individuals in the united states1 z although sks are benign growths, these lesions are often cosmetically bothersome to patients, and over 60% of individuals with sks have reported taking measures to hide or disguise their sks2 z current treatments for sks involve surgical or ablative modalities such as liquid nitrogen cryotherapy, shave removal, curettage, chemical peels, and laser treatments2,3 z recently, a proprietary hydrogen peroxide topical solution, 40% (w/w) (hp40) was approved by the us food and drug administration for the treatment of adults with raised sks4 z the phase 4, open-label seborrheic keratoses of the face, neck and décolletage (sk-fan) study was designed to assess participants’ satisfaction following hp40 treatment of sks located on these body regions objective z the objective of this presentation is to describe the methodology of the ongoing sk-fan study methods study design z the sk-fan study is a phase 4, open-label, single-group trial (nct03487588) that is currently ongoing at 3 sites in the united states z a schematic of the study design is presented in figure 1 and the detailed timing of key study procedures is summarized in table 1 z during the study, hp40 is applied to all target lesions at visit 2, then again at visits 5 (day 15) and 7 (day 29) if target lesions meet the retreatment criterion (see “investigational product and treatments” section) z assessments of participant satisfaction with hp40 treatment take place during visits 2, 3, 6, 8, 10, and 11 (see “subject satisfaction assessment” [ssa] section) figure 1. study design sc re en in gpatients with 3 evaluable sk lesions on face, neck, and décolletage 113 days visit 1 open-label study period visit 8 visit 3 visit 4 visit 5 visit 6 visit 7 visit 9 visit 10 visit 11/eos subject satisfaction assessment: visits 2, 3, 6, 8, 10, and 11 hp40 treatment: visit 2; visits 5 and 7 if retreatment criterion met visit 2 eos, end of study; hp40, hydrogen peroxide topical solution, 40% (w/w); sk, seborrheic keratosis. table 1. timing of key study procedures study visit: 1 2 3 4 5 6 7 8 9 10 11 treatment day: −13 to 0 1 2 8 15 22 29 36 57 85 113 allowable window: n/a n/a n/a ±1 day ±1 day ±1 day ±1 day ±1 day ±7 days ±7 days ±7 days treatment with hp40 x xa xa physician lesion assessment x x x x x x x x subject satisfaction assessment x x x x x x adverse events x x x x x x x x x x hp40, hydrogen peroxide topical solution, 40% (w/w); n/a, not applicable. aif retreatment criterion met. study participants z the targeted enrollment of the sk-fan study is 30 participants z key inclusion and exclusion criteria are described in table 2 table 2. key inclusion and exclusion criteria of the sk-fan study key inclusion criteria z male or female, 30–75 years of age z have a diagnosis of stable, clinically typical sks, with 3 target sks — 2 target sks must be located on the face — 1 target sk must be located on the neck or décolletage — target sks are required to: y have a physician lesion assessment™ (pla) grade of ≥2 on a 4-point scale (0 = clear; 1 = near clear; 2 = thin [≤1 mm]; 3 = thick [>1 mm]) y have a diameter of 5–15 mm y have a clinically typical appearance y be a discrete lesion y not be covered with hair that would interfere with study medication treatment or study evaluations y not be in an intertriginous fold, on the eyelids, within 5 mm of the orbital rim, or pedunculated z patients may also have up to 4 nontarget sks on the face, neck, or décolletage 2 the study will also assess how patient satisfaction correlates with efficacy 3 the study is currently ongoing with results expected early in 2019 skin january 2019 volume 3 issue 1 copyright 2018 the national society for cutaneous medicine 1 clinical management recommendations how to manage onychomycosis abigail m smith, bs1, boni e elewski, md1 1department of dermatology, university of alabama at birmingham, birmingham, al the role of oral antifungal medications in treating onychomycosis continues to be revisited as new topical antifungal medications are developed. efinaconazole and tavaborole, for example, are generally safe and may be preferred by patients. however, oral antifungals may be required for some patients to be adequately treated. the purpose of this article is to provide a quick reference for the clinical management of onychomycosis with maximum efficacy and minimal side effects in mind. we will address the following questions: 1) how do you diagnose onychomycosis? 2) what is the role of oral antifungals? 3) what is the role of topical antifungals? 4) when are oral medications really necessary? 5) what are dermatophytomas and how should they be treated? we conclude that terbinafine is the current gold standard for treating tinea unguium, particularly when patients suffer from comorbidities such as diabetes, immunosuppression, or psoriasis. topical antifungals may stand alone or act as adjunct therapy to improve efficacy and maintain response, though ease of application for patients and cost are important considerations. further, efinaconazole solution applied to the subungual space has proven effective in cases of onychomycosis complicated by a dermatophytoma. only 50% of nail dystrophies are caused by fungal pathogens, so confirmatory laboratory testing to establish the diagnosis of onychomycosis is important before treatment is initiated, and can be done by pas or koh (showing septate hyphae) and/or by fungal culture or pcr to identify the causative pathogen. while pas stain is considered more sensitive than koh preparation, it is significantly more expensive. although both fungal culture and pcr identify the pathogen, it may take up to 6 weeks for a result. alternatively, a recent paper suggested treatment with oral terbinafine after clinical confirmation alone without laboratory testing is cost-effective.1 oral antifungals for onychomycosis include terbinafine, itraconazole, or fluconazole, and all of these are effective against dermatophyte fungi that most commonly cause onychomycosis. of these, terbinafine has a low cost, superior efficacy, and lacks significant drug-drug interactions, so is usually considered first line treatment.2-3 it is effective against dermatophytes, but not candida or non-dermatophyte molds. how do you diagnose onychomycosis? what is the role of oral antifungals? skin january 2019 volume 3 issue 1 copyright 2018 the national society for cutaneous medicine 2 terbinafine is dosed at 250 mg daily for 6 weeks in fingernails and for 12 weeks in toenail involvement, but a more prolonged course is often required in patients with extensive infection. the most common adverse event associated with terbinafine is gastrointestinal upset, but dysgeusia and cutaneous drug reactions ranging from a mild morbilliform eruption to toxic epidermal necrolysis have been reported which is why empiric treatment is not always without consequence.4-5 also, be on the alert for terbinafine resistance which has been recently reported.6 itraconazole is more expensive than terbinafine but may be useful in cases of terbinafine intolerance or nonresponsiveness and in non-dermatophyte infections. its spectrum of activity includes dermatophytes, non-dermatophyte molds and yeasts including candida. itraconazole is dosed at 200 mg daily for three to four continuous months or alternatively (pulsed) 400 mg daily for one week per month for three to four months. caution is needed in patients with congestive heart failure and patients who are taking statins due to the drug’s potent inhibition of cyp3a4 leading to an increased risk of rhabdomyolysis.7 there are other drug-drug interactions as well, so intermittent dosing may be preferred in patients on multiple medications. fluconazole is not fda-approved for the treatment of onychomycosis but is approved for this indication in many other countries and, like itraconazole, has a broad spectrum of activity. a pivotal study compared once weekly dosing of 150, 300, or 450 mg fluconazole and showed excellent results (table 1).8 however, one or two 200 mg tablets taken together once weekly is a practical option that can be continued until the nail is clear. this drug is generally well tolerated and is even approved in children for table 1. complete and mycologic cure rates for commonly used oral and topical antifungals. complete cure* (%) mycologic cure (%) terbinafine9 38 70 itraconazole10 14 54 fluconazole11 37 – 48** 47 – 62** efinaconazole12 15.2 – 17.8 53.4 – 55.2 tavaborole13 6.5 – 9.1 31.1 – 35.9 ciclopirox15 5.5 – 8.5 29 – 36 *complete cure is defined as normal nail plus mycologic cure. **per package label. different indications. complete and mycologic cure rates from phase iii clinical studies are in table 1. topical antifungals may be used either alone or in combination with systemic agents and include efinaconazole 10% solution and tavaborole 5% solution. both of these agents are effective in vitro against dermatophytes, non-dermatophyte molds, and yeasts but were studied exclusively in cases of nail dermatophytosis. efinaconazole 10% was approved in 2014, and phase iii studies showed a 53.4 55.2% mycologic cure rate and a 15.2-17.8% complete cure rate when applied daily for 48 weeks (table 1).12 tavaborole 5% is a novel boron-containing solution with a low molecular weight that easily penetrates the nail plate. phase iii trials showed a 31.1 – 35.9% mycologic cure rate and a 6.5-9.1% complete cure rate when what is the role of topical antifungals? skin january 2019 volume 3 issue 1 copyright 2018 the national society for cutaneous medicine 3 applied daily for 48 weeks (table 1).13 the superior efficacy of efinaconazole 10% is likely due to its low surface tension which allows for greater subungual distribution.14 however, our experience is that these agents have better clinical efficacy than data suggest. other topical options include ciclopirox 8% or amorolfine 5% lacquer. both medications are applied to the nail plate and contiguous skin for 48 weeks. mycologic and complete cure rates for ciclopirox 8% lacquer are 29-36% and 5.5-8.5% respectively, and are similar to tavaborole.15 amorolfine is not available in the us. the limitation of ciclopirox and amorolfine is the lacquer vehicle that leaves behind a film on the nail plate surface which, after multiple applications, can compromise diffusion of the agent through the nail plate. additionally, it is difficult to apply the lacquer in the subungual space where the dermatophyte resides. topical treatment also has a role in improving efficacy and maintaining response to systemic treatment. topical treatment may also reduce the total amount of antifungal agent required. for example, the addition of daily ciclopirox 8% lacquer to intermittent oral terbinafine (250 mg daily for four weeks followed by a four-week drug holiday and an additional four weeks of terbinafine) has shown comparable efficacy to 12 weeks of continuous terbinafine.16 limiting exposure to oral agents over time may limit adverse effects. additional data has shown that 250 mg terbinafine for 12 weeks plus amorolfine 5% applied once every 2 weeks delayed recurrence of nail disease by 200 days.17 while these data include the older topical antifungals, it is reasonable to assume that adjunct therapy with newer topical agents would show similar results. although treatment with topical antifungals avoids systemic side effects, it is important to remember that topical therapies may not be feasible for patients whose movements are limited by severe arthritis or body habitus. certain patients may require treatment with oral antifungals and are unlikely to respond to topical agents. these include patients with primary or secondary immunosuppression. impaired cell-mediated immunity often manifests itself in changes in the nails, hair, and skin. a study by chang et al. in nondermatological patients reported that 70% of patients with mycotic leukonychia, a mixed form of white superficial onychomycosis (wso) and proximal subungual onychomycosis (pso), also suffered from immunosuppression.18 while primary immunodeficiency syndromes are rare, patients with hiv or patients on chronic immunosuppressive therapies are commonly encountered. other comorbidities such as diabetes, peripheral vascular disease, and nail psoriasis result in relative immunodeficiency from compromised blood flow at the site of infection. for example, a multi-center study looked at psoriatic patients with toenail onychodystrophy and found that 27% of these patients had positive mycology (defined as either koh positive or culture positive for a dermatophyte). 19 a later systematic review found a prevalence of 18% among psoriatic patients compared to 9.1% among the control group.20 thus, these patients need agents that readily absorb through the nail plate and accumulate at high concentrations for adequate treatment of their infection. terbinafine is the most economical and effective treatment for when are oral medications really necessary? skin january 2019 volume 3 issue 1 copyright 2018 the national society for cutaneous medicine 4 dermatophytosis in these patients. itraconazole is preferred when covering nondermatophyte molds and yeasts. dermatophytomas are orange or yellow longitudinal streaks or patches in the nail bed composed of compacted dermatophyte hyphae and surrounded by a biofilm (figure 1a). dermatophytomas do not respond well to oral antifungal agents likely because the biofilm blocks penetration of the drug. though patients with dermatophytomas were excluded from phase iii efinaconazole trials, a recent case study indicated that topical efinaconazole 10% is effective as the sole treatment for a dermatophytoma.21 an additional phase iv trial showed complete resolution of all 20 dermatophytomas that were treated with efinaconazole 10% for 48 weeks (figure 1a and 1b).22 • patients with onychomycosis desire to be treated, often because of embarrassment and disfigurement associated with their disease. nails also provide a function that if lost can make simple tasks such as scratching or buttoning a shirt challenging. • oral antifungals used in onychomycosis have been available for about 25 years, and they are generally both effective and safe. terbinafine is the current gold standard. • topical agents are also effective and may be used as adjunct treatment to systemic medications or as monotherapy. they are more expensive than the oral medications but offer an excellent safety profile and are generally preferred by patients. the newer solutions offer more flexibility in delivery and can be applied in the subungual space. figure 1: a) left great toe with onychomycosis and a dermatophytoma present prior to treatment with efinaconazole 10%. b) left great toe after treatment with efinaconazole 10% for 48 weeks. conflict of interest disclosures: dr. elewski has been a consultant, in which she received and honorarium, for the following companies: celgene, leo, lilly, novartis, pfizer, sun, and valeant. dr. elewski has received clinical research support (funds paid to the university of alabama at birmingham) from the following companies: abbvie, boehringer ingelheim, celgene, incyte, leo, lilly, merck, novartis, pfizer, regeneron, sun, and valeant. funding: none. what are dermatophytomas and how should they be treated? how should physicians discuss onychomycosis with patients? a b skin january 2019 volume 3 issue 1 copyright 2018 the national society for cutaneous medicine 5 corresponding author: abigail m smith, bs university of alabama at birmingham birmingham, al amcmurry@uab.edu references: 1. mikailov a, cohen j, joyce c, mostaghimi a. cost-effectiveness of confirmatory testing before treatment of onychomycosis. jama dermatol. 2016;152(3):276–281. doi:10.1001/jamadermatol.2015.4190 2. sá dcd, lamas apb, tosti a. oral therapy for onychomycosis: an evidence-based review. american journal of clinical dermatology. 2014;15(1):17-36. doi:10.1007/s40257-013-0056-2 3. arikan sr, einarson tr, kobelt-nguyen g, schubert f. a multinational pharmacoeconomic analysis of oral therapies for onychomycosis: the onychomycosis study group. br j dermatol. 1994; 130(suppl. 43): 35-44. 4. beltraminelli hs, lerch m, arnold a, et al. acute generalized exanthematous pustulosis induced by the antifungal terbinafine: case report and review of literature. br j dermatol. 2005; 152(4): 780-783, doi:10.1111/j.13652133.2005.06393.x. 5. carstens j, wendelboe p, sogaard h, thestruppedersen k. toxic epidermal necrolysis and erythema multiforme following therapy with terbinafine. acta derm venereol. 1994; 74(5): 391-392. 6. yamada t, maeda m, alshahni mm, et al. terbinafine resistance of trichophyton clinical isolates caused by specific point mutations in the squalene epoxidase gene. antimicrob agents chemother. 2017;61(7):e00115-17. published 2017 jun 27. doi:10.1128/aac.00115-17 7. dybro am, damkier p, rasmussen tb, hellfritzsch m. statin-associated rhabdomyolysis triggered by drug-drug interaction with itraconazole. bmj case rep. 2016:brc2016216457, doi:10.1136/bcr-2016-216457 8. rich p, scher rk, breneman d, et al. pharmacokinetics of three doses of once-weekly fluconazole (150, 300, and 450 mg) in distal subungual onychomycosis of the toenail. journal of the american academy of dermatology. 1998;38(6). doi:10.1016/s01909622(98)70493-1 9. lamisil (terbinafine hcl) [package insert]. novartis pharmaceuticals corporation, east hanover, nj; 2012. 10. sporanox (itraconazole) [package insert]. janssen pharmaceuticals inc, titusville, nj; 2012. 11. diflucan (fluconazole) [package insert]. pfizer inc, new york city, ny; 2011. 12. elewski be, rich p, pollak r, et al. efinaconazole 10% solution in the treatment of toenail onychomycosis: two phase iii multicenter, randomized, double-blind studies. j am acad dermatol. 2013; 68(4): 600-608, doi: 10.1016/j.jaad.2012.10.013 13. elewski be, aly r, baldwin sl, et al. efficacy and safety of tavaborole topical solution, 5%, a novel boron-based antifungal agent, for the treatment of toenail onychomycosis: results from 2 randomized phase-iii studies. j am acad dermatol. 2015; 73(1): 62-69, doi: 10.1016/j.jaad.2015.04.010 14. elewski be, pollak ra, pillai r, olin jt. access of efinaconazole topical solution, 10%, to the infection site by spreading through the subungual space. j drugs dermatol. 2014; 13(11): 13941398. 15. gupta ak, fleckman p, baran r. ciclopirox nail lacquer topical solution mailto:amcmurry@uab.edu skin january 2019 volume 3 issue 1 copyright 2018 the national society for cutaneous medicine 6 8% in the treatment of toenail onychomycosis. j am acad dermatol. 2000; 43(4 suppl.): s70-s80. 16. gupta ak. ciclopirox topical solution, 8% combined with oral terbinafine to treat onychomycosis: a randomized, evaluator-blinded study. j drugs dermatol. 2005; 4(4): 481-485. 17. sigurgeirsson b, olafsson jh, steinsson jt, et al. efficacy of amorolfine nail lacquer for the prophylaxis of onychomycosis over 3 years. j eur acad dermatol venereol. 2010; 24(8): 910915, doi: 10.1111/j.14683083.2009.03547.x. 18. chang p, arenas r, cabrera l. mycotic leukonychia in nondermatologic patients. report of 10 cases. dermatología cmq. 2010;8:8–12. 19. gupta ak, lynde cw, jain hc, sibbald rg, elewski be, daniel cr 3rd, et al. a higher prevalence of onychomycosis in psoriatics compared with nonpsoriatics: a multicentre study. br j dermatol. 1997;136:786-789. 20. klaassen k, dulak m, kerkhof pvd, pasch m. the prevalence of onychomycosis in psoriatic patients: a systematic review. journal of the european academy of dermatology and venereology. 2013;28(5):533-541. doi:10.1111/jdv.12239 21. cantrell w, canavan t, elewski b. report of a case of a dermatophytoma successfully treated with topical efinaconazole 10% solution. j drugs dermatol. 2015; 14(5): 524-526. 22. wang c, cantrell w, canavan t, elewski b. successful treatment of dermatophytomas in 19 patients using efinaconazole 10% solution. skin appendage disord. in press. skin december 2018 volume 2 supplemental issue copyright 2018 the national society for cutaneous medicine 101 rising derm stars optical coherence tomography for the scalp chloe ekelem md1 1uc irvine, irvine ca the advancement of technology-based diagnostic and therapeutic modalities are rapidly changing the dermatology practice by allowing clinicians to expand noninvasive indications. hair loss disorders afflict people of all subtypes, are difficult to treat, and are disruptive to the psychological wellbeing of patients.1,2 scalp biopsies remain cumbersome, invasive procedures that permit only single time-point analysis. clinicians are often left to gauge treatment efficacy or disease progression over time subjectively, which may limit ability to treat these conditions optimally. real-time assessment of living tissue has invaluable potential for bolstering histologic and dermatoscopic characterization of follicular disorders of the skin, particularly alopecia. optical coherence tomography (oct) is an imaging technology that offers safe and effective noninvasive examination of skin. this technology is fundamentally analogous to ultrasound, but uses infrared interferometry to generate depth-resolved images from backscattered light.3 its high resolution output allows visualization of the epidermis, upper dermis, dermal-epidermal junction, blood vessels, and skin appendages.4 our analysis shows that oct technology is nondiscriminatory and can obtain reliable data in different fitzpatrick skin types among multiethnic populations. as applications for oct continually expand, this study aims to determine its utility in subsurface structural analysis for inflammatory and follicular diseases of the scalp. we successfully devised an imaging cap to precisely relocate scalp areas, captured images that minimize data loss to light absorption, and described parameters of follicular disease, such as number of follicles, hair thickness, presence and absence of doublets and triplets, as well as epidermal thickness. we record these measurements across separate 5x7x1.3 mm areas in common alopecia locations including frontal, vertex, and temporal scalp. twenty subjects with alopecia (10 scarring and 10 non-scarring) were compared to 5 control subjects for epidermal thickness, hair follicle quantity and diameter. control subjects were expected to have larger average follicular diameter and higher average hair-bearing follicle density compared to alopecia subjects in all scalp regions. preliminary results show significant variation in measurements of control subjects based on ethnicity and hair type. no significant differences exist between alopecia subjects and controls in unaffected scalp locations. epidermal thickness is significantly larger in scarring alopecia subjects compared to nonskin december 2018 volume 2 supplemental issue copyright 2018 the national society for cutaneous medicine 102 scarring and control subjects. scarring patients exhibit higher proportions of doublets and triplets than non-scarring control subjects. and ratio of follicle to hair shaft diameter was not significantly different across subject groups. image characteristics learned from this analysis will serve as an atlas for future follicular application of oct in hair disease diagnosis, prognosis, and therapy assessment. references: references: 1. meyer, m, and da mcgrouther. “a study relating wound tension to scar morphology in the pre-sternal scar using langers technique.” british journal of plastic surgery, vol. 44, no. 4, may 1991, pp. 291–294., doi:10.1016/0007 1226(91)90074-t. 2. carruthers, jean d.a., and j. alastair carruthers. “treatment of glabellar frown lines with c. botulinum-a exotoxin.” the journal of dermatologic surgery and oncology, vol. 18, no. 1, 1992, pp. 17–21., doi:10.1111/j.1524 4725.1992.tb03295.x presented at fall clinical dermatology | las vegas, nevada | october 18–21, 2018. previously presented at the 5th world psoriasis and psoriatic arthritis conference 2018 objective • to understand the frequency of inadequate response to first-line biologic therapies in patients with psoriasis, and the reasons underlying this lack of response, in a real-world setting. frequency of inadequate response to treatment among psoriasis patients on first-line biologics a. sheahan,1 e. lee,2 l. pisenti,2 m. yassine,2 r. suruki1 1ucb pharma, raleigh, nc; 2ucb pharma, smyrna, ga background • plaque psoriasis (pso) is an immune-mediated inflammatory disease, affecting around 3% of adults in the united states1,2 and 2–6% in europe.3 • pso can have a substantial impact on patients’ quality of life, with psychosocial and emotional effects such as depression and fatigue in addition to physical symptoms.4 • whilst treatment of patients with moderate to severe disease with biologic agents such as tumor necrosis factor inhibitors (anti-tnfs), anti-interleukin (il)-17s and anti-il12/13s is well-established, suboptimal efficacy or adverse events may require switching to another biologic to improve patient outcomes. • however, studies describing the occurrence of inadequate response (ir) to biologic treatments in the real-world setting are currently lacking. • an understanding of the frequency and reasons underlying ir may help to identify and address unmet treatment needs. methods study design and inclusion criteria • a retrospective analysis of a commercial us healthcare claims database was conducted, including claims data from 2012–2016. • included patients had: – a qualifying pso icd-9/10 code – initiated treatment with an anti-tnf approved for pso, secukinumab, ustekinumab or apremilast (index date) – ≥1 year of database enrollment both before and after the index date • patients with prior biologic exposure in the year prior to the index date were excluded. definition of ir • ir was defined as: 1. ≥1 claim with a biologic dose >110% of the label-recommended dose for ≥30 days (“above-label dosing”) 2. cessation (>2 months with no treatment) of a 1st line biologic (“non-switch discontinuation”) 3. cessation of a 1st line biologic followed by initiation of a new biologic within 2 months (“switch to another biologic”) 4. addition of a corticosteroid, immunosuppressant, or biologic with ≥30 days’ supply overlap (“add-on treatment”) results treatment response outcomes • of 13,995 patients who met the inclusion criteria, 10,213 (73.0%) experienced an ir event in the 12-month follow-up period. – the most common ir event was non-switch discontinuation (figure 1) %, unless otherwise stated inadequate response (n=10,213) no inadequate response (n=3,782) age (years), mean 46.2 47.0 female 52.1 46.7 history of systemic treatment 56.1 54.4 index biologic adalimumab 44.4 37.3 etanercept 27.5 23.7 apremilast 12.7 18.8 ustekinumab 11.7 13.9 infliximab 1.9 3.7 secukinumab 0.7 1.2 golimumab 0.7 0.9 certolizumab pegol 0.4 0.5 most frequent comorbidities and those of interest psoriatic arthritis 30.7 31.1 hypertension 30.6 31.3 hyperlipidemia 29.7 31.3 anxiety 9.8 8.9 depression 13.5 11.1 table 1. patient demographics and index biologic use systemic treatment: any prescribed non-biologic therapy indicated for the management of pso. figure 1. distribution of response outcomes across index biologics ir: inadequate response. references: 1. rachakonda td. et al. j am acad dermatol 2014;70:512–6; 2. kurd sk. et al. j am acad dermatol 2009;60:218–24; 3. danielsen k. et al. br j dermatol 2013;168:1303–10; 4. langley rg. et al. ann rheum dis 2005; 64:ii18–23. author contributions: substantial contributions to study conception/design, or acquisition/ analysis/interpretation of data: as, el, lp, my, rs; drafting of the publication, or revising it critically for important intellectual content: as, el, lp, my, rs; final approval of the publication: as, el, lp, my, rs. author disclosures: as, el, lp, my, rs are employees of ucb pharma. acknowledgements: this study was funded by ucb pharma. the authors would like to thank david friesen (hays pharma) and paul murray (hays pharma) for assistance with data analysis, mylene serna, phd, ucb pharma, smyrna, usa, for publication coordination and helen chambers, dphil, costello medical, cambridge, uk for medical writing and editorial assistance. all costs associated with development of this poster were funded by ucb pharma. conclusions • inadequate response in first line pso biologic treatment is common, with non-switch discontinuation being the most frequent type. • analysis of the longer-term outcomes of non-switch discontinuation patients may help to better characterize the reasons these patients are not persistent on the first line biologic; currently it is difficult to determine why patients would discontinue without initiating an alternate biologic. • this highlights an opportunity to optimize available treatment options, and better understand patient needs. • therapeutic options with improved durability may help optimize the management of pso, but further analysis is necessary to identify underlying causes of ir. 0.8 0.6 0.4 0.2 0.0 1.0 p ro b a b ili ty o f re m a in in g in f o llo w -u p 0 2 4 6 8 10 12 time to ir event (months) ir (all qualifying events) above-label dosing switch to other biologic non-switch discontinuation add-on treatment time to ir event (months) all ir events (n=10,213) above-label dosing (n=2,144) switch to another biologic (n=1,324) non-switch discontinuation (n=5,901) add-on treatment (n=844) mean (sd) 4.6 (3.1) 4.6 (2.7) 5.5 (2.9) 4.4 (3.2) 4.1 (3.3) median (q1–q3) 3.8 (2.0–6.6) 3.7 (2.8–6.3) 5.1 (3.2–7.6) 3.7 (1.8–6.5) 3.3 (1.4–6.3) figure 3. time to ir events ir: inadequate response; sd: standard deviation; q1–q3: interquartile range. figure 2. response outcomes by index biologic above-label dosing was not assessed for infliximab and ustekinumab (due to weight-based dosing). ir: inadequate response. figure 4. treatment persistence in patients switching to another biologic figure 5. add-on treatments by baseline therapy non-switch discontinuation 42% non-ir 27% above-label dosing 15% switch to another biologic 10% add-on treatment 6% 80 60 40 20 100 0 % p at ie n ts etanercept (n=3708) certolizumab pegol (n=64) ustekinumab (n=1719) golimumab (n=102) apremilast (n=2013) secukinumab (n=117) infliximab (n=330) adalimumab (n=5942) 42.4 6.7 23.6 27.3 37.6 19.7 29.1 5.1 33.3 44.1 12.7 24.2 10.8 18.0 41.2 23.8 10.7 35.6 24.3 30.5 62.1 29.7 46.9 10.9 35.4 49.8 non-ir above-label dosing switch to another biologicnon-switch discontinuation add-on treatment 5.5 3.9 5.9 5.6 8.5 9.0 6.9 2.9 3.5 12.50.2 not persistent 30% persistent 70% not persistent 47% persistent 53% 3 months after switch 6 months after switch 90 80 70 60 50 40 30 20 10 100 0 % p at ie n ts overall 15.4 63.9 bl biologic monotherapy bl concomitant systemic corticosteroid bl concomitant immunosuppressive biologic immunosuppressive systemic corticosteroid 20.7 15.6 19.0 65.4 3.9 11.8 84.3 0.9 47.4 51.8 treatment at baseline • demographics and characteristics, including the distribution of index biologics, were similar in patients who did and did not experience ir (table 1). • the proportion of ir by index biologic ranged from 76.2% in adalimumab to 57.6% in infliximab (figure 2). time to inadequate response • across all ir groups, mean time from initiation of 1st line biologic to ir was 4.6 months (standard deviation [sd] =3.1). • time to ir tended to be numerically higher in patients switching to another biologic (mean=5.5 months, sd=2.9) (figure 3). biologic switch patients • among patients switching to another biologic, 70.5% of patients were persistent on the new biologic after 3 months, vs 53.5% after 6 months (figure 4). • most frequently used biologics after treatment switch were ustekinumab (29.7% of switch patients) and adalimumab (28.7% of switch patients). add-on treatment patients • overall, most frequent add-on therapies were immunosuppressive drugs (63.9%) followed by systemic corticosteroids (20.7%) and biologics (15.4%) (figure 5). • 73.3% of these patients subsequently discontinued the add-on therapy before discontinuing their biologic. conclusions • in the largest prospective study reported in patients with metastatic cscc, cemiplimab 3 mg/kg q2w showed substantial activity and durable responses with an acceptable safety profile. • cemiplimab showed an acceptable risk/benefit profile in this metastatic cscc population, which tends to be elderly and associated with medical co-morbidities. • combined with the updated cscc expansion cohorts of the phase 1 results, these results indicate that advanced cscc tumors, whether metastatic or locally advanced, are responsive to cemiplimab. • evaluation of cemiplimab 3 mg/kg q2w in patients with locally advanced cscc in the phase 2 study of cemiplimab is ongoing. these results in combination with the phase 1 results are now published and available at http://nejm.org (migden mr and rischin d et al. n engl j med. 2018;379:341–351). references 1. rogers hw et al. jama dermatol. 2015;151:1081–1086. 2. stratigos a et al. eur j cancer. 2015;51:1989–2007. 3. kauvar an et al. dermatol surg. 2015;41:1214–1240. 4. karia ps et al. j am acad dermatol. 2013;68:957–966. 5. macdonald le et al. proc natl acad sci. 2014;111:5147–5152. 6. murphy aj et al. proc natl acad sci. 2014;111:5153–5158. 7. burova e et al. mol cancer ther. 2017;16:861–870. 8. papadopoulos kp et al. j clin oncol. 2017;35(suppl;abstr 9503). 9. eisenhauer ea et al. eur j cancer, 2009;45:228–247. acknowledgments we thank the patients, their families, and all investigators involved in this study. the study was funded by regeneron pharmaceuticals, inc., and sanofi. medical writing support and typesetting was provided by emmanuel ogunnowo of prime, knutsford, uk, funded by regeneron pharmaceuticals, inc., and sanofi. copies of this poster obtained through quick response (qr) code are for personal use only and may not be reproduced without permission from the author of this poster. primary analysis of phase 2 results for cemiplimab, a human monoclonal anti-pd-1, in patients with metastatic cutaneous squamous cell carcinoma danny rischin,1 michael r. migden,2 anne lynn s. chang,3 christine h. chung,4 lara a. dunn,5 alexander guminski,6 axel hauschild,7 leonel hernandez-aya,8 brett g.m. hughes,9 karl d. lewis,10 annette m. lim,11 badri modi,12 dirk schadendorf,13 chrysalyne d. schmults,14 jocelyn booth,15 siyu li,15 kosalai mohan,16 elizabeth stankevich,15 israel lowy,16 matthew g. fury16 1department of medical oncology, peter maccallum cancer centre, melbourne, australia; 2departments of dermatology and head and neck surgery, university of texas md anderson cancer center, houston, texas, usa; 3department of dermatology, stanford university school of medicine, ca, usa; 4department of head and neck-endocrine oncology, h. lee moffitt cancer center and research institute, fl, usa; 5department of medicine, head and neck medical oncology, memorial sloan kettering cancer center, ny, usa; 6department of medical oncology, royal north shore hospital, st leonards, australia; 7schleswig-holstein university hospital, kiel, germany; 8division of medical oncology, department of medicine, washington university school of medicine, mo, usa; 9royal brisbane & women’s hospital and university of queensland, brisbane, australia; 10university of colorado denver, school of medicine, co, usa; 11department of medical oncology, sir charles gairdner hospital, perth, australia; 12division of dermatology, city of hope, ca, usa; 13university hospital essen, essen and german cancer consortium, essen, germany; 14department of dermatology, brigham and women’s hospital, harvard medical school, ma, usa; 15regeneron pharmaceuticals inc., basking ridge, nj, usa; 16regeneron pharmaceuticals inc., tarrytown, ny, usa. • key exclusion criteria: ongoing or recent (within 5 years) autoimmune disease requiring systemic immunosuppression prior treatments with anti-pd-1 or anti-pd-l1 therapy history of solid organ transplant, concurrent malignancies (unless indolent or not considered life threatening; for example, basal cell carcinoma), or hematologic malignancies. • severity of treatment-emergent adverse events (teaes) was graded according to the national cancer institute common terminology criteria for adverse events (version 4.03). • the data cut-off date for this analysis was october 27, 2017. results baseline characteristics, disposition, and treatment exposure • of the 59 patients enrolled, 35 (59.3%) remained on treatment at the time of data cut-off, 24 (40.7%) have discontinued treatment mainly due to disease progression (n=14; 23.7%) and adverse events (aes) (n=4; 6.8%). • the median duration of exposure to cemiplimab was 32.7 weeks (range: 2.0–69.3) and the median number of doses administered was 17 (range: 1–35). • the median duration of follow-up at the time of data cut-off was 7.9 months (range: 1.1–15.6). clinical efficacy • rapid, deep, and durable target lesion reductions were observed in most patients who had at least one tumor assessment on treatment (figures 2–4). group 1 – adult patients with metastatic (nodal and/or distant) cscc • key inclusion criteria: – ecog performance status of 0 or 1 – adequate organ function, – at least one lesion measurable by recist version 1.1. cemiplimab 3 mg/kg q2w iv, for up to 96 weeks (retreatment optional for patients with disease progression during follow-up) tumor response assessment by an independent central review committee. tumor imaging every 8 weeks for the assessment of efficacy (confirmatory scans performed no sooner than 4 weeks following initial documentation of tumor response) figure 1. phase 2 (group 1) study design ecog, eastern cooperative oncology group; iv, intravenously; q2w, every 2 weeks. month 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 100 80 60 40 20 0 –20 –40 –60 –80 –100 p er ce nt c ha ng e in ta rg et le si on s fr om b as el in e figure 3. change in target lesion over time plot shows the percent change in target lesion diameters from baseline over time. patients shown in this figure are the same as those in figure 2. horizontal dotted lines indicate criteria for partial response (≥30% decrease in the sum of target lesion diameters) and progressive disease (≥20% increase in the target lesion diameters). table 1. patient demographics and baseline characteristics metastatic cscc (n = 59) median age, years (range) 71 (38–93) ≥ 65 years, n (%) 43 (72.9) male sex, n (%) 54 (91.5) ecog performance status, n (%) 0 23 (39.0) 1 36 (61.0) primary cscc site, n (%) head/neck† 38 (64.4) extremity‡ 12 (20.3) trunk 9 (15.3) prior systemic therapy for cscc, n (%) 33 (55.9) prior radiotherapy for cscc, n (%) 50 (84.7) †includes ear and temple. ‡includes arms/hands and legs/feet. 100 80 60 40 20 –100 –80 –60 –40 –20 0 b es t p er ce nt c ha ng e in ta rg et le si on fr om b as el in e complete response/partial response not evaluable progressive disease stable disease figure 2. clinical activity of tumor response to cemiplimab in patients who underwent radiologic evaluation per independent central review plot shows the best percentage change in the sum of target lesion diameters from baseline for 45 patients who underwent radiologic evaluation per independent central review after treatment initiation. lesion measurements after progression were excluded. horizontal dotted lines indicate criteria for partial response (≥30% decrease in the sum of target lesion diameters) and progressive disease (≥20% increase in the target lesion diameters). three patients with target lesion reductions ≥30% were classified as progressive disease (red bars) due to new lesion or progression of non-target lesion. the following patients do not appear in the figure (but are included in the orr analysis [table 2], per intention-to-treat): three patients with progression of non-target lesions or new lesion (but no evaluable target lesion), one patient with complete response who had only non-target lesions at baseline, four patients with best response of non-complete response/non-progressive disease, and six patients with no evaluable post-treatment tumor assessments. one patient had stable disease per recist 1.1 but was not evaluable (yellow bar) due to externally visible disease that was not evaluable on photographic assessments. table 2. tumor response assessment by independent central review metastatic cscc (n = 59) best overall response, n (%) complete response 4 (6.8) partial response 24 (40.7) stable disease 9 (15.3) non-complete response/ non-progressive disease† 4 (6.8) progressive disease 11 (18.6) not evaluable‡ 7 (11.9) overall response rate, % (95% ci) 47.5 (34.3–60.9) durable disease control rate, % (95% ci)§ 61.0 (47.4–73.5) median observed time to response, months (range)¶ 1.9 (1.7–6.0) †patients with non-measurable disease on central review of baseline imaging. ‡includes missing and unknown tumor response. §defined as the proportion of patients without progressive disease for at least 105 days. ¶data shown are from patients with confirmed complete or partial response; n = 28. ci, confidence interval. figure 4. time to and duration of response in responding patients plot shows time to response and duration of response in the 28 responding patients. each horizontal line represents one patient. twenty-three of the 28 patients remain in response and on study at time of data cut-off. three patients had disease progression (red asterisks); one patient was censored after surgical resection of responding target lesion (top line); and one was lost to follow-up after experiencing complete response (second-from-top line). 0 2 4 6 8 10 month 12 14 16 18 complete response partial response stable disease progressive disease unable to evaluate non-complete response/partial response surgical removal of target lesion ongoing treatment ongoing study p at ie nt s w ith r es po ns e table 3. teaes regardless of attribution teaes metastatic cscc (n = 59) n (%) any grade grade ≥3 any 59 (100.0) 25 (42.4) serious 21 (35.6) 17 (28.8) led to discontinuation 4 (6.8) 3 (5.1) with an outcome of death 3 (5.1) 3 (5.1) occurred in at least five patients† diarrhea 16 (27.1) 1 (1.7) fatigue 14 (23.7) 1 (1.7) nausea 10 (16.9) 0 constipation 9 (15.3) 1 (1.7) rash 9 (15.3) 0 cough 8 (13.6) 0 decreased appetite 8 (13.6) 0 pruritus 8 (13.6) 0 headache 8 (13.6) 0 dry skin 6 (10.2) 0 maculo-papular rash 6 (10.2) 0 vomiting 6 (10.2) 0 anemia 5 (8.5) 1 (1.7) hypothyroidism 5 (8.5) 0 increased alanine aminotransferase 5 (8.5) 0 pneumonitis 5 (8.5) 2 (3.4) †events are listed as indicated on the case report form. adverse events were coded according to preferred terms (meddra version 20.0). although rash and maculopapular rash may reflect the same condition, they were listed as two distinct events in the safety report. included in this table are teaes of any grade that occurred in ≥5 patients. events are listed in decreasing order of frequency by any grade. • pneumonitis was the only grade ≥3 treatment-related teae to occur in more than one patient. • three patients (5.1%) had teaes with outcome of death; however, none were considered related to treatment. a 93-year-old man presented with fever and cough with purulent sputum, and died of complications of pneumonia. a 72-year-old man died in his sleep. a 90-year-old man who had disease progression (per independent review) developed duodenal ulcer and esophagitis that later resolved. the patient subsequently experienced hypercalcemia and deep vein thrombosis and died. • responses to cemiplimab were observed irrespective of prior systemic therapy. orr in patients without prior systemic anticancer therapy was 57.7% (15/26 patients; 95% ci: 36.9–76.6; three crs and 12 prs); durable dcr was 69.2% (95% ci: 48.2–85.7). orr in patients who had received prior systemic anticancer therapy was 39.4% (13/33 patients; 95% ci: 22.9–57.9; one cr and 12 prs); durable dcr was 54.5% (95% ci: 36.4–71.9). treatment-emergent adverse events • teaes regardless of attribution are summarized in table 3. • grade ≥3 teaes that occurred in more than one patient were cellulitis, pneumonitis, hypercalcemia, death, and pleural effusion. • investigator-assessed treatment-related teaes of any grade occurred in 44 patients (74.6%), with seven patients (11.9%) experiencing grade ≥3 treatment-related teaes. • a total of nine grade ≥3 immune-related teaes (per investigator assessment) occurred in six patients (10.2%) as follows: pneumonitis (3.4%), and arthritis, aseptic meningitis, colitis with diarrhea, confusional state, hypophysitis, neck pain, and polyarthritis (each 1.7%). • four patients (6.8%) discontinued treatment due to treatment-related teaes, with three patients (5.1%) discontinuing due to grade ≥3 treatment-related teaes. • the most common treatment-related teaes were fatigue (13.6%), diarrhea (11.9%), and pruritus, rash, and maculopapular rash (each 10.2%). • median duration of response had not been reached at data cut-off. • neither median pfs nor median os had been reached at data cut-off. the estimated progression-free probability at 12 months was 52.5% (95% ci: 37.0–65.8). the estimated probability of survival at 12 months was 80.6% (95% ci: 67.7–88.8). figure 5. examples of reductions in visible cscc lesions following treatment with cemiplimab the patient in panel a is an 85-year-old man with supraclavicular lesion who had received prior radiotherapy. the patient in panel b is an 83-year-old man with multiple prior surgeries for cscc. the patient in panel c is a 66-year-old man with anterior chest wall cscc lesions who had received prior cisplatin. a baseline week 32 b baseline week 8 c baseline week 24 poster presented at the 2018 fall clinical dermatology conference, october 18–21, las vegas, nevada (encore of asco 2018 poster presentation). background • cutaneous squamous cell carcinoma (cscc) is rivalled in incidence only by basal cell carcinoma as the most common cancer in the us.1 • risk factors for cscc include chronic sun exposure, advanced age, ultraviolet radiation-sensitive skin, and immunosuppression.2 • more than 95% of cscc patients are cured with surgery; however, due to the very high incidence of the disease, an estimated 3,932–8,791 patients died from cscc in 2012 in the us.3,4 • there is no approved systemic therapy for patients with advanced cscc (locally advanced cscc that is no longer amenable to surgery or radiation therapy, and metastatic cscc). • cemiplimab (regn2810) is a high-affinity, highly potent, human, hinge-stabilized igg4 monoclonal antibody, generated using velocimmune® technology,5,6 directed against programmed death-1 (pd-1) receptor blocking the interactions of pd-1 with pd-ligand 1 (pd-l1) and pd-l2.7 • cemiplimab treatment demonstrated encouraging preliminary activity in the cscc expansion cohorts of the first-in-human study.8 • here we present the primary analysis of the metastatic cscc cohort from the phase 2 study of cemiplimab in patients with advanced cscc (nct02760498). objectives • the primary objective was to evaluate overall response rate (orr; complete response + partial response) according to independent central review per response evaluation criteria in solid tumors (recist) 1.19 (for scans) and modified world health organization criteria (for photos). • secondary objectives include: estimation of duration of response, durable disease control rate (dcr), progression-free survival (pfs), and overall survival (os) assessment of safety and tolerability of cemiplimab. methods • patients with metastatic cscc from group 1 of the phase 2, non-randomized, global, pivotal trial of cemiplimab in patients with advanced cscc are included in this analysis (figure 1). skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 348 brief articles crospovidone induced vasculopathy of the skin brian j. simmons, md1, brian s. hoyt, md2, konstantinos linos, md2, shaofeng yan, md2, kathryn a. zug, md1 1dartmouth hitchcock medical center, section of dermatology department of surgery, 18 old etna rd, lebanon, nh 03766 2dartmouth hitchcock medical center, department of pathology, 1 medical center dr., lebanon, nh 03756 the rate of opiate abuse in the united states continues to rise, with over 4 million cases of non-medical use of prescriptions per year. 1 the ramifications of the epidemic can be see across a wide variety of medical specialties including dermatology. dermatologists play a critical role in recognizing skin signs of drug abuse, such as levamisole associated vasculopathy from adulterated cocaine. crospovidone is an insoluble disintegrant commonly found in pharmaceutical tablets. drug users searching for a quicker high from opioids opt to crush the tablets and inject them intravenously. when tablets containing the excipient crosprovidone are crushed and injected, it can result in a vasculopathy. this has been described previously in the lungs2, but to our knowledge this is an unrecognized cause of vasculopathy of the skin. a 46-year-old man with a past medical history of intravenous drug use (ivdu), alcohol abuse and chronic hepatitis c presented with new onset left hand swelling, redness and tenderness for 4 days. the patient was originally seen at an outside hospital and given ceftriaxone with minimal improvement. patient denied recent trauma to the area or recent ivdu; however, the patient’s drug screen was positive for opioids and on further questioning he did endorse recent injection drug use. on physical exam there were dusky red to violaceous purpuric macules and patches on the first and second digit and the thenar eminence (fig1). given the presentation and clinical history, the differential diagnosis included vasculopathy (due to cryoglobulinemia or levamisole) or a thromboembolic process. however, lab workup demonstrated a negative rheumatoid factor, negative cryoglobulins, negative blood cultures, and a normal white blood cell count. moreover, in combination with an asymmetric distribution along the distal radial artery, this raised concern for an alternative cause of vasculopathy. subsequent punch biopsy was performed of the hand. hematoxylin and eosin stain showed a blue to purple coral-shaped foreign substance within the vascular lumen (fig2a&b). congo red highlighted the foreign substance with a similar morphology (fig2c&d). crospovidone has been reported to cause angiothrombosis in lungs 2 and found incidentally in gastrointestinal tract biopsies.3 introduction case report skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 349 patients can crush tablets and inject them, introducing the insoluble foreign material into the dermis. on histologic sections, crospovidone stains violet-blue on h&e, bright red on mucicarmine and red-brown on congo-red. although the material can resemble calcium histologically, von kossa stain is negative. the pathogenesis in the skin appears to be by thromboembolic occlusion of vessels, similar to that seen in the lungs. given the critical role that dermatologists play in the workup of skin signs of drug abuse, it is important that providers recognize this uncommon and likely underreported complication of drug abuse. prompt recognition of this entity can be beneficial to patients and their providers alike. as in other causes of vasculopathy, supportive therapy with wound care, monitoring for wound site infections and in this case referral to a substance abuse program is imperative to prevent further occurrences. figure 1. red to dusky violaceous purpuric macules and patches on the first and second digit. figure 2. a) hematoxylin and eosin stain highlighting blue to purple coral-shaped foreign material within the vascular lumen (10x) b) high powered view of crospovidone material within vascular lumen on h&e (20x) c) congo red highlighted the foreign substance with a similar morphology within vascular lumen (10x) d) high powered view of crospovidone highlighted by congo red (20x). conflict of interest disclosures: none funding: none corresponding author: brian j. simmons, md one medical center drive, lebanon, nh 03756 603-650-3156 brian.j.simmons@hitchcock.org references: 1. mathis sm, hagemeier n, hagaman a, dreyzehner j, pack rp. a dissemination and implementation science approach to the epidemic of opioid use disorder in the united states. curr hiv/aids rep. 2018. 2. ganesan s, felo j, saldana m, kalasinsky vf, lewin-smith mr, tomashefski jf, jr. embolized crospovidone (poly[n-vinyl-2-pyrrolidone]) in the lungs of intravenous drug users. mod pathol. 2003;16(4):286-292. 3. shaddy sm, arnold ma, shilo k, et al. crospovidone and microcrystalline cellulose: a novel description of pharmaceutical fillers in the gastrointestinal tract. am j surg pathol. 2017;41(4):564-569. mailto:brian.j.simmons@hitchcock.org poster presented at the presented at the 36th fall clinical dermatology conference | las vegas, nv | october 12-15, 2017 maintenance of response with certolizumab pegol for the treatment of chronic plaque psoriasis: 48-week results from two ongoing phase 3, multicenter, randomized, placebo-controlled studies (cimpasi-1 and cimpasi-2) kristian reich,1 andrew blauvelt,2 diamant thaçi,3 craig leonardi,4 yves poulin,5 daniel burge,6 luke peterson,7 janice drew,6 catherine arendt,8 alice b. gottlieb9 1dermatologikum hamburg and sciderm research institute, hamburg, germany; 2oregon medical research center, portland, or; 3university of lübeck, lübeck, germany; 4central dermatology and saint louis university school of medicine, st. louis, mo; 5centre de recherche dermatologique du québec métropolitain, québec, canada; 6dermira, inc., menlo park, ca; 7ucb biosciences, inc., raleigh, nc; 8ucb pharma, brussels, belgium; 9new york medical college, valhalla, ny introduction • psoriasis affects ~3% of adults in the us1,2 and ~2-6% in europe,3 and most patients develop the disease in the third decade of life4 • therapy for patients with chronic plaque psoriasis varies per the severity of the disease, with topical therapies and/or phototherapy used to treat limited or mild psoriasis and photochemotherapy, cyclosporine, methotrexate, apremilast, or biologics such as tumor necrosis factor (tnf) inhibitors, anti-il17s, and anti-il12/23s used to treat moderateto-severe forms • certolizumab pegol (czp) is the only pegylated, fc-free, anti-tnf biologic currently under development for the treatment of moderate-to-severe chronic plaque psoriasis and has demonstrated positive results in previous psoriasis trials5,6 • cimpasi-1 (nct02326298) and cimpasi-2 (nct02326272) are ongoing phase 3 trials designed to assess the efficacy and safety of czp compared with placebo; results from the first 48 weeks of the two studies are presented here methods study design • cimpasi-1 and cimpasi-2 are replicate, phase 3, multicenter studies conducted in north america and europe, consisting of randomized, double-blind, placebo-controlled periods for the first 48 weeks followed by 96 weeks of open-label observation • patients were randomized 2:2:1 to czp 400 mg every 2 weeks (q2w), czp 200 mg q2w (following 400 mg loading dose at weeks 0, 2, 4), or placebo q2w for 16 weeks (figure 1) • at week 16, patients continued to receive treatment through week 48 according to the following criteria: – czp 400 mg q2wand czp 200 mg q2w-treated psoriasis area and severity index (pasi) 50 responders (≥50% reduction in pasi) continued to receive their initial blinded treatment – placebo-treated week 16 pasi 75 responders (≥75% reduction in pasi) continued blinded placebo treatment; pasi 50-75 responders (≥50% but <75% reduction in pasi) received czp 200 mg q2w (following 400 mg loading dose at weeks 16, 18, 20) – pasi 50 nonresponders at week 16 entered the escape arm and received unblinded czp 400 mg q2w • pasi 50 nonresponders at week 32, 40, or 48 were withdrawn from the study figure 1. study design 0 randomization 16 484032week initial treatment period (double-blind) maintenance period (double-blind)screening 1:2:2 2 4 placebo q2w ld ≥ pasi 75 ld pasi 50-75 < pasi 50-withdrawn < pasi 50-withdrawn < pasi 50-withdrawn < pasi 50-withdrawn < pasi 50 < pasi 50 < pasi 50 czp 200 mg q2w czp 400 mg q2w escape czp 400 mg q2w czp, certolizumab pegol; ld, czp 400 mg loading dose at weeks 0, 2 and 4 or weeks 16, 18 and 20; pasi 50, ≥50% reduction in psoriasis area and severity index (pasi); pasi 50-75, ≥50% but <75% reduction in pasi; pasi 75, ≥75% reduction in pasi; q2w, every 2 weeks patients • eligible patients were ≥18 years of age and had moderate-to-severe chronic plaque psoriasis for ≥6 months (pasi ≥12, affected body surface area [bsa] ≥10%, physician’s global assessment [pga; 5-point scale] ≥3) • patients had to be candidates for systemic psoriasis therapy, phototherapy, and/or photochemotherapy • patients were excluded if they had previous treatment with czp or >2 biologics (including anti-tnf); had history of primary failure to any biologic or secondary failure to >1 biologic; had erythrodermic, guttate, or generalized pustular psoriasis types; or had history of current, chronic, or recurrent viral, bacterial, or fungal infections study assessments • coprimary endpoints were pasi 75 and pga 0/1 (‘clear’ or ’almost clear’ with ≥2-category improvement) at week 16 • secondary endpoints reported here were pasi 90 at week 16 and pasi 75 and pga 0/1 at week 48; pasi 90 at week 48 was included as an additional endpoint • safety evaluation included assessment of treatment-emergent adverse events (teaes) statistical analysis • all efficacy analyses were performed on the randomized set (all randomized patients) • logistic regression models with factors of treatment group, region, and prior biologic exposure (yes/no) were used to analyze pasi 75, pga 0/1, and pasi 90 responder rates (week 16) – the markov chain monte carlo (mcmc) method for multiple imputation was used to account for missing data7 • safety assessments were performed on the safety set, which included all randomized patients who received ≥1 dose of study medication results patient disposition, demographics, and baseline characteristics • in both studies, at least 90% of patients in each treatment arm completed week 16, and the highest week 16 completion rates were in the czp 400 mg q2w treatment group (figure 2) • of those patients who entered the blinded maintenance period in cimpasi-1|cimpasi-2, 90.9%|88.4% of czp 400 q2w patients and 95.9%|84.2% czp 200 mg q2w patients completed week 48 (figure 2) • baseline pasi and pga scores were comparable across treatment groups for both studies (table 1) • roughly one-third of study participants reported prior biologic use, and the proportion across treatment arms was similar (table 1) figure 2. patient disposition completed wk 16 cimpasi-1 cimpasi-2screened n=286 randomized n=234 screened n=301 randomized n=227 placebo n=51 n=46 (90.2%) discontinued 5 adverse event 0 lack of efficacy 1 protocol violation 0 lost to follow-up 1 consent w/d 3 other 0 discontinued 3 adverse event 0 lack of efficacy 0 protocol violation 0 lost to follow-up 1 consent w/d 2 other 0 discontinued 1 adverse event 1 lack of efficacy 0 protocol violation 0 lost to follow-up 0 consent w/d 0 other 0 discontinued 4 adverse event 0 lack of efficacy 0 protocol violation 0 lost to follow-up 1 consent w/d 3 other 0 discontinued 7 adverse event 3 lack of efficacy 0 protocol violation 0 lost to follow-up 2 consent w/d 2 other 0 discontinued 4 adverse event 1 lack of efficacy 0 protocol violation 0 lost to follow-up 0 consent w/d 1 other 2 czp 200 mg q2w n=95 ≥pasi 50 and entered maintenance completed wk48 discontinued 3 consent w/d 1 other 1 <pasi 50 1 n=74 discontinued 7 lost to follow-up 1 consent w/d 3 other 1 <pasi 50 2 n=5a n=3a discontinued 12 adverse event 3 lack of efficacy 2 lost to follow -up 2 consent w/d 3 <pasi 50 2 discontinued 8 adverse event 4 lack of efficacy 1 consent w/d 1 other 1 <pasi 50 1 discontinued 1 consent w/d 1 discontinued 2 adverse event 2 n=77c czp 400 mg q2w n=88 placebo n=49 czp 200 mg q2w n=91 czp 400 mg q2w n=87 n=92 (96.8%) n=87 (98.9%) n=87 (98.9%) escapeb n=38 escapeb n=38 escapeb n=18 escapeb n=18 escapeb n=8 escapeb n=8 escapeb n=34 escapeb n=34 escapeb n=8 escapeb n=8 escapeb n=12 escapeb n=12 n=70 (90.9%) n=70 (90.9%) n=5 (100%) n=5 (100%) n=3 (100%) n=3 (100%) n=71 (95.9%) n=71 (95.9%) n=45 (91.8%) n=76n=5a n=6a n=69d n=84 (92.3%) n=83 (95.4%) n=83 (95.4%) n=61 (88.4%) n=61 (88.4%) n=3 (60.0%) n=3 (60.0%) n=5 (83.3%) n=5 (83.3%) n=64 (84.2%) n=64 (84.2%) aupon entering maintenance period, placebo-treated pasi 75 responders (≥75% reduction in pasi) continued blinded placebo treatment; pasi 50-75 responders (≥50% but <75% reduction in pasi) received czp 200 mg q2w bpasi 50 nonresponders at week 16 received open-label czp 400 mg q2w in the escape arm of the study (not part of this report) ctwo patients completed week 16 but did not enter maintenance period due to adverse events dtwo patients completed week 16 but did not enter maintenance period (1 loss to follow-up; 1 consent withdrawn) czp, certolizumab pegol; pasi 50, 50% reduction in psoriasis area and severity index (pasi); q2w, every 2 weeks; w/d, withdrawn table 1. patient demographics and baseline disease characteristics cimpasi-1 cimpasi-2 placebo (n=51) czp 200 mg q2w (n=95) czp 400 mg q2w (n=88) placebo (n=49) czp 200 mg q2w (n=91) czp 400 mg q2w (n=87) demographics age (years), mean ± sd 47.9 ± 12.8 44.5 ± 13.1 43.6 ± 12.1 43.3 ± 14.5 46.7 ± 13.3 46.4 ± 13.5 male, n (%) 35 (68.6) 67 (70.5) 60 (68.2) 26 (53.1) 58 (63.7) 43 (49.4) white, n (%) 45 (88.2) 87 (91.6) 79 (89.8) 44 (89.8) 86 (94.5) 81 (93.1) geographic region, n (%) north america europe 26 (51.0) 25 (49.0) 49 (51.6) 46 (48.4) 45 (51.1) 43 (48.9) 35 (71.4) 14 (28.6) 61 (67.0) 30 (33.0) 61 (70.1) 26 (29.9) weight (kg), mean ± sd 95.2 ± 19.5 92.6 ± 21.0 92.2 ± 21.7 87.1 ± 26.4 97.8 ± 25.6 91.8 ± 27.7 bmi (kg/m2), mean ± sd 32.2 ± 6.8 31.1 ± 7.3 30.7 ± 6.7 30.2 ± 8.0 32.8 ± 8.3 31.7 ± 8.9 baseline disease characteristics duration of psoriasis at screening (years), mean ± sd 18.5 ± 12.9 16.6 ± 12.3 18.4 ± 12.9 15.4 ± 12.2 18.8 ± 13.5 18.6 ± 12.4 concurrent psa,a n (%) 4 (7.8) 10 (10.5) 15 (17.0) 9 (18.4) 22 (24.2) 26 (29.9) pasi score, mean ± sd 19.8 ± 7.5 20.1 ± 8.2 19.6 ± 7.9 17.3 ± 5.3 18.4 ± 5.9 19.5 ± 6.7 dlqi score, mean ± sd 13.9 ± 8.3 13.3 ± 7.4 13.1 ± 6.5 12.9 ± 7.3 15.2 ± 7.2 14.2 ± 7.2 bsa (%), mean ± sd 26.1 ± 16.1 25.4 ± 16.9 24.1 ± 16.6 20.0 ± 9.5 21.4 ± 12.2 23.1 ± 11.6 pga score, n (%) 3: moderate 4: severe 35 (68.6) 16 (31.4) 62 (65.3) 33 (34.7) 65 (73.9) 23 (26.1) 37 (75.5) 12 (24.5) 66 (72.5) 25 (27.5) 61 (70.1) 26 (29.9) prior biologic use,b n (%) anti-tnf anti-il17 15 (29.4) 10 (19.6) 3 (5.9) 30 (31.6) 19 (20.0) 8 (8.4) 29 (33.0) 17 (19.3) 4 (4.5) 14 (28.6) 9 (18.4) 2 (4.1) 32 (35.2) 22 (24.2) 8 (8.8) 30 (34.5) 22 (25.3) 4 (4.6) any prior systemic psoriasis treatment, n (%) 36 (70.6) 66 (69.5) 61 (69.3) 36 (73.5) 65 (71.4) 63 (72.4) apresence of concurrent psa was self-reported bpatients may have had exposure to >1 prior biologic but ≤2 per exclusion criteria bmi, body mass index; bsa, body surface area; czp, certolizumab pegol; dlqi, dermatology life quality index; il, interleukin; pasi, psoriasis area and severity index; pga, physician’s global assessment; psa, psoriatic arthritis; q2w, every 2 weeks; tnf, tumor necrosis factor coprimary endpoints • at week 16, responder rates were greater for czp 400 mg q2w and 200 mg q2w versus placebo for pasi 75 and pga 0/1 (p<0.0001 for all) (figure 3, figure 4) secondary endpoints • czp 400 mg q2w and 200 mg q2w pasi 75 responder rates were maintained to week 48 (figure 3) • pga 0/1 responder rates were also maintained to week 48 for patients who continued to receive either dose of czp during the maintenance period (figure 4) • at week 16, pasi 90 responder rates were greater for czp 400 mg q2w and 200 mg q2w versus placebo (p<0.0001 for both) (figure 5) • pasi 90 responder rates continued to improve beyond week 16 and the difference between dose groups increased by week 48 in cimpasi-1 (figure 5) figure 3. pasi 75 responder rates from baseline to week 48 cimpasi-1 week week cimpasi-2 80 100 60 40 20 0 r es po nd er r at e (% ) 0 2 4 8 12 16 20 24 28 32 40 48 80 100 60 40 20 0 r es po nd er r at e (% ) 0 2 4 8 12 16 20 24 28 32 40 48 placebo (n=51) czp 200 mg q2wa (n=95) czp 400 mg q2w (n=88) 6.5% 11.6% placebo (n=49) czp 200 mg q2wa (n=91) czp 400 mg q2w (n=87) 66.5% 67.2% 81.4% 78.7% 75.8% 87.1% 82.6% 81.3% *p<0.05, **p<0.0001 versus placebo aczp 200 mg q2w patients received loading dose of czp 400 mg at weeks 0, 2, and 4 based on logistic regression model with factors for treatment, region, and prior biologic exposure (yes/no) week 16 pasi 50 nonresponders were imputed as nonresponders throughout the maintenance period; all other missing data were imputed via multiple imputation (mcmc method) czp, certolizumab pegol; mcmc, markov chain monte carlo; pasi 75, ≥75% reduction in psoriasis area and severity index; q2w, every 2 weeks figure 4. pga 0/1 responder rates from baseline to week 48 cimpasi-1 week week cimpasi-2 80 100 60 40 20 0 r es po nd er r at e (% ) 0 2 4 8 12 16 20 24 28 32 40 48 80 100 60 40 20 0 r es po nd er r at e (% ) 0 2 4 8 12 16 20 24 28 32 40 48 placebo (n=51) czp 200 mg q2wa (n=95) czp 400 mg q2w (n=88) 4.2% 2.0% placebo (n=49) czp 200 mg q2wa (n=91) czp 400 mg q2w (n=87) 47.0% 52.7% 66.8% 72.6% 57.9% 69.5% 71.6% 66.6% *p<0.05, **p<0.0001 versus placebo aczp 200 mg q2w patients received loading dose of czp 400 mg at weeks 0, 2, and 4 based on logistic regression model with factors for treatment, region, and prior biologic exposure (yes/no) week 16 pasi 50 nonresponders were imputed as nonresponders throughout the maintenance period; all other missing data were imputed via multiple imputation (mcmc method) czp, certolizumab pegol; mcmc, markov chain monte carlo; pga 0/1, ‘clear’ or ‘almost clear’ with ≥2 category improvement (on 5-point scale) in physician’s global assessment; q2w, every 2 weeks figure 5. pasi 90 responder rates from baseline to week 48 cimpasi-1 week week cimpasi-2 80 100 60 40 20 0 r es po nd er r at e (% ) 0 2 4 8 12 16 20 24 28 32 40 48 80 100 60 40 20 0 r es po nd er r at e (% ) 0 2 4 8 12 16 20 24 28 32 40 48 placebo (n=51) czp 200 mg q2wa (n=95) czp 400 mg q2w (n=88) 0.4% 4.5% placebo (n=49) czp 200 mg q2wa (n=91) czp 400 mg q2w (n=87) 35.8 42.8% 52.6% 59.6% 43.6% 60.2% 55.4% 62.0% *p<0.05, **p<0.0001 versus placebo aczp 200 mg q2w patients received loading dose of czp 400 mg at weeks 0, 2, and 4 based on logistic regression model with factors for treatment, region, and prior biologic exposure (yes/no) week 16 pasi 50 nonresponders were imputed as nonresponders throughout the maintenance period; all other missing data were imputed via multiple imputation (mcmc method) czp, certolizumab pegol; mcmc, markov chain monte carlo; pasi 90, ≥90% reduction in psoriasis area and severity index; q2w, every 2 weeks safety • for czp 400 mg q2w and 200 mg q2w vs placebo, teae|serious teae incidence rates per 100 patient-years from baseline to week 16 were 375.9|19.0 and 292.3|6.9 vs 297.1|6.8 in cimpasi-1, and 405.7|15.3 and 308.7|7.4 vs 388.9/0 in cimpasi-2 • for czp 400 mg q2w and 200 mg q2w, teae|serious teae incidence rates per 100 patient-years was lower from baseline to week 48 compared with rates per 100 patient-years from baseline to week 16 (257.6|10.4 and 218.3|5.3 in cimpasi-1, and 277.5|7.5 and 236.0|9.7 in cimpasi-2) (table 2) • one serious infection was reported in the czp 400 mg q2w group in cimpasi-1, and one in the czp 400 mg q2w group in cimpasi-2; one death, due to motor vehicle accident, was reported in the czp 400 mg q2w group in cimpasi-1 (table 2) • after 48 weeks of treatment, teaes occurring in >10% of all czp-treated patients were nasopharyngitis and upper respiratory tract infection (table 3) table 2. adverse events from baseline to week 48 cimpasi-1 cimpasi-2 czp 200 mg q2w (n=100)g czp 400 mg q2w (n=144)g czp 200 mg q2w (n=95)g czp 400 mg q2w (n=129)g teaes, n (%) [incidence ratea] all 72 (72.0) [218.3] 111 (77.1) [257.6] 73 (76.8) [236.0] 103 (79.8) [277.5] serious 4 ( 4.0) [ 5.3] 11 ( 7.6) [ 10.4] 7 ( 7.4) [ 9.7] 7 ( 5.4) [ 7.5] discontinuations due to teae, n (%)b 0 5 (3.5) 8 (8.4) 8 (6.2) deaths, n (%)b 0 1 (0.7) 0 0 teaes of interest, n (%) [incidence ratea] infections and infestations 50 (50.0) [102.5] 76 (52.8) [115.9] 48 (50.5) [98.1] 68 (52.7) [111.2] latent tuberculosis 0 1 ( 0.7) [ 0.9] 0 0 active tuberculosis 0 0 0 0 candida infections 1 ( 1.0) [ 1.3]c 0 1 ( 1.1) [ 1.4]d 2 ( 1.6) [ 2.1]d,e oral fungal infection 0 0 0 1 ( 0.8) [ 1.0] fungal skin infection 0 1 ( 0.7) [ 0.9] 0 0 herpes zoster 0 0 1 ( 1.1) [ 1.4] 0 herpes dermatitis 0 0 0 1 ( 0.8) [ 1.0] epstein-barr viral infection 0 0 1 ( 1.1) [ 1.4] 0 serious infections 0 1 ( 0.7) [ 0.9] 0 1 ( 0.8) [ 1.1] non-melanoma skin cancerf 0 1 ( 0.7) [ 0.9] 0 1 ( 0.8) [ 1.1] malignancy (excluding non-melanoma skin cancer) 0 0 0 0 ibd flare 0 0 0 0 depression 0 2 ( 1.4) [ 1.8] 1 ( 1.1) [ 1.4] 2 ( 1.6) [ 2.1] aincidence of new cases per 100 subject-years bincidence rate not calculated coral candidiasis dvulvovaginal candidiasis enail candida fboth malignancies were basal cell carcinomas gpatients who switched doses could have been counted in both czp doses patients initially randomized to czp 200 mg q2w who received czp 400 mg q2w in the escape arm were counted in both czp doses czp, certolizumab pegol; ibd, inflammatory bowel disease; teae, treatment-emergent adverse event table 3. most frequently reported teaes (≥5% in any group): baseline to week 48 n (%), [incidence ratea] cimpasi-1 cimpasi-2 czp 200 mg q2w (n=100)b czp 400 mg q2w (n=144)b czp 200 mg q2w (n=95)b czp 400 mg q2w (n=129)b nasopharyngitis 28 (28.0) [46.5] 40 (27.8) [46.9] nasopharyngitis 17 (17.9) [26.4] 25 (19.4) [29.0] urti 12 (12.0) [17.2] 13 ( 9.0) [12.8] urti 11 (11.6) [16.1] 13 (10.1) [14.5] arthralgia 6 ( 6.0) [ 8.2] 2 ( 1.4) [ 1.8] hypertension 5 ( 5.3) [ 7.2] 8 ( 6.2) [ 8.6] headache 6 ( 6.0) [ 8.2] 12 ( 8.3) [11.7] urinary tract infection 5 ( 5.3) [ 7.1] 5 ( 3.9) [ 5.3] pruritus 2 ( 2.1) [ 2.8] 8 ( 6.2) [ 8.8] pharyngitis 6 ( 6.3) [ 8.5] 3 ( 2.3) [ 3.2] bronchitis 2 ( 2.1) [ 2.8] 7 ( 5.4) [ 7.5] aincidence of new cases per 100 subject-years bpatients who switched doses could have been counted in both czp doses patients initially randomized to czp 200 mg q2w who received czp 400 mg q2w in the escape arm were counted in both czp doses czp, certolizumab pegol; teae, treatment-emergent adverse event; urti, upper respiratory tract infection conclusions • treatment with czp 400 mg q2w or czp 200 mg q2w for 16 weeks was associated with statistically significant, clinically meaningful improvements for all endpoints analyzed (pasi 75, pga 0/1, and pasi 90) compared with placebo • response rates were maintained at week 48 with both czp doses • for most measures, improvement at both week 16 and week 48 was numerically greatest in patients receiving czp 400 mg q2w • teaes were consistent with the known safety profile of anti-tnf therapy and no new safety signals were observed with czp at any dose over 48 weeks references 1. rachakonda et al. j am acad dermatol. 2014;70(3):512-6. 2. kurd et al. j am acad dermatol. 2009;60(2):218-24. 3. danielsen et al. br j dermatol. 2013;168(6):1303-10. 4. farber et al. dermatologica. 1974;148(1):1-18. 5. reich et al. br j dermatol. 2012;167(1):180-90. 6. gladman et al. arthritis care res (hoboken). 2014;66(7):1085-92. 7. sun. application of markov chain monte-carlo multiple imputation method to deal with missing data from the mechanism of mnar in sensitivity analysis for a longitudinal clinical trial. in: chen et al. monte-carlo simulation-based statistical modeling. singapore: springer; 2017:233-52. acknowledgements this study and all costs associated with the development of this poster were funded by dermira, inc. dermira and ucb are in a strategic collaboration to evaluate the efficacy and safety of certolizumab pegol in the treatment of moderate-tosevere plaque psoriasis. medical writing support was provided by prescott medical communications group (chicago, il). author disclosures kr: speaker’s fees, honoraria, and/or advisory board: abbvie; amgen; biogen; boehringer ingelheim pharma; celgene; centocor; covagen; forward pharma; glaxosmithkline; janssen-cilag; leo pharma; eli lilly; medac; merck sharp & dohme; novartis; ocean pharma; pfizer; regeneron; takeda; ucb pharma; xenoport. ab: consulting honoraria, clinical investigator, and/or speaker’s fees: abbvie; amgen; boehringer ingelheim pharma; celgene; dermira, inc.; genentech; glaxosmithkline; janssen; eli lilly; merck; novartis; pfizer; regeneron; sandoz; sanofi genzyme; sun pharma; ucb pharma; valeant. dt: consultant for: abbvie, biogen-idec, celgene, dignity, galapagos, maruho, mitsubishi, novartis, pfizer and xenoport. scientific advisory board: abbvie, amgen, biogen-idec, celgene, eli-lilly, glaxosmithkline, leo pharma, pfizer, novartis, janssen, mundipharma; sandoz. cl: speaker’s fees, honoraria, and/or advisory board: abbvie; actavis; amgen; boehringer ingelheim pharma; celgene; coherus; corrona; dermira, inc.; eli lilly; galderma; glenmark; janssen; leo pharma; merck; novartis; pfizer; sandoz; stiefel; ucb pharma; vitae; wyeth. yp: investigator (research grants): abbvie; baxter; boehringer ingelheim pharma; celgene; centocor/janssen; eli lilly; emd serono; glaxosmithkline; leo pharma; medimmune; merck; novartis; pfizer; regeneron; takeda; ucb pharma. speaker (honoraria): abbvie; celgene; janssen; eli lilly; leo pharma; novartis; regeneron sanofi genzyme. associate editor of the journal of cutaneous medicine and surgery. db, jd: employees of dermira, inc. lp, ca: employees of ucb pharma. abg: consulting and/or advisory board agreements: abbvie, aclaris, amicus, allergan, behring, beiersdorf, inc., bristol myers squibb co., celgene corp., csl merck, dermira, development crescendo bioscience, incyte, janssen inc., lilly, novartis, pfizer, ucb, reddy labs, sun pharmaceutical industries, valeant, xenoport. research/educational grants (paid to tufts medical center): janssen incyte. fc17posterdermirareichmaintenanceofresponse48wks.pdf microsoft word 17. 617 proof done.docx skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 94 short communications asymmetric prurigo nodularis after paralysis: a case report justin chu ba,1 jordan genece ba,1 yasmin amir md,1 mark g. lebwohl, md1 1icahn school of medicine at mount sinai, department of dermatology prurigo nodularis (pn) is defined by hyperkeratotic pruritic nodules most commonly localized symmetrically on the bilateral extensor lower extremities.1 the disorder is characterized by intense pruritus which leads to a vicious itch-scratch cycle. this itch-scratch cycle promotes chronic excoriated nodules that can result in nodular lichenification, hyperkeratosis, hyperpigmentation, and skin thickening.2 while the exact etiology is not fully understood, a broad variety of diseases have been reported to underlie pn including atopic dispositions, several systemic diseases, infections, and psychiatric and neurologic disorders.3 treatment options for pn generally target the itch-scratch cycle. here we present the case of an 82-year-old female with right-sided paralysis after stroke, presenting with asymmetrical distribution of papules and nodules over her extremities. we present the case of an 82-year-old woman with a history of psoriasis, hypertension, diabetes mellitus, and a stroke in december 2014, leading to right-sided paralysis. she initially presented to our clinic with a chief complaint of worsening pruritus. she had previously been treated with topical steroids, calcipotriene, and apremilast without success. clinical examination revealed hyperpigmented papules and nodules with overlying erosions and ulcerations. the papules and nodules were more prominent on the right arm and left leg (figure 1). a skin biopsy of the left leg revealed a dense eosinophilic infiltrate with scattered mononuclear cells and areas of fibrosis. clinical and histologic findings were consistent with a diagnosis of prurigo nodularis. interestingly, due to the patient’s right-sided paralysis, lesions were localized to the right arm and left leg, those areas easiest for her to scratch. the left arm and right leg which were difficult to reach introduction case report prurigo nodularis (pn) is a chronic cutaneous condition characterized by hyperkeratotic pruritic nodules and a vicious itch-scratch cycle. the exact etiology of pn is unclear and thus it remains difficult to treat. here we present a case of an 82-year-old female with pn and right-sided paralysis after a stroke, uniquely presenting with pn lesions localized to her right arm and left leg only on the sites which she would easily scratch after her stroke. this case highlights the importance of managing pruritus in pn patients as the patient presented with a drastically reduced affliction on hard to reach areas due to her paralysis. abstract skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 95 following her stroke were dramatically less involved. figure 1. prurigo nodules on the patient’s arms (a) and legs (b). (a) (b) our case underscores the importance of the itch-scratch cycle in the propagation of prurigo nodularis. our patient presented with an asymmetric distribution of her prurigo lesions secondary to right-sided paralysis after stroke. the disparity between the presence of nodules on the right arm and left leg and the absence of nodules on the left arm and right leg highlights the importance of itch-scratch cycle and its propagation of the disease.5 since the patient is unable to easily scratch her left arm and right leg, these extremities are less affected. while the exact etiology of pn remains unclear, our case highlights the direct relationship between skin nodules and ability to scratch. in an overwhelming majority of patients, pruritus or a pruritus-associated dermatosis is found to be the etiologic cause. treating the underlying pruritus should therefore be of paramount importance. new drugs like the neurokinin receptor antagonists and antibodies to il-31 are promising as neurokinin receptors contribute to itch transmission and il-31 is known as the itch cytokine.6 our patient presented with an asymmetric distribution of prurigo nodules due to her underlying right-sided paralysis, highlighting the role of the itch-scratch cycle in the pathogenesis of prurigo nodularis and the importance of managing underlying pruritus in the treatment of this complex disease. discussion conclusion skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 96 conflict of interest disclosures: none funding: none corresponding author: justin chu ba department of dermatology icahn school of medicine at mount sinai email: justin.chu@mssm.edu references: 1. hyde jn (1883) a practical treatise on diseases of the skin, for the use of students and practitioners, 1st edn. lea & febiger, philadelphia.(hyde 1894) 2. hammes, s. , hermann, j. , roos, s. and ockenfels, h. (2011), uvb 308-nm excimer light and bath puva: combination therapy is very effective in the treatment of prurigo nodularis. journal of the european academy of dermatology and venereology, 25: 799-803. 3. iking, a. , grundmann, s. , chatzigeorgakidis, e. , phan, n. , klein, d. and ständer, s. (2013), prurigo as a symptom of atopic and non-atopic diseases: aetiological survey in a consecutive cohort of 108 patients. journal of the european academy of dermatology and venereology, 27: 550-557. 4. zeidler c, yosipovitch g, ständer s. prurigo nodularis and its management. dermatol clin. 2018 jul;36(3):189–97. 5. alfadley, a. , al-hawsawi, k. , thestrup-pedersen, k. and al-aboud, k. (2003), treatment of prurigo nodularis with thalidomide: a case report and review of the literature. international journal of dermatology, 42: 372-375. 6. tan, w. s., & tey, h. l. (2014). extensive prurigo nodularis: characterization and etiology. dermatology, 228(3), 276-280. skin july rlet 1189 proof returned skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 388 research letter assessing comfort in conducting research among medical students interested in dermatology carmen carlos, ba1, christen brown, ms1, erika elliott, md1, andrea murina, md1 1tulane university school of medicine, department of dermatology, new orleans, la usa conducting research in medical school can foster a commitment to lifelong learning. formal research instruction includes activities such as self-directed learning (sdl) and problem-based learning (pbl), as well as sessions in evidence based medicine (ebm).1,2 however, skills gained from isolated activities such as these may be limited. though research during medical school has increasingly become an expectation, high numbers of research projects may not indicate competence in all research-related skills. the assessment of research activity is frequently based on project outcomes rather than evaluation of the skills required for successful completion of research projects.35 frameworks have been developed that define the skills deemed essential for medical research,6 but many do not provide an assessment tool.7,8 the literature lacks a clear conceptual framework9 to assess abstract introduction: participation in research has become increasingly popular amongst us medical students hoping to match into dermatology residency. while medical students have increasingly high research output by the time of graduation, the preparedness of medical students for independent research is unknown. methods: an anonymous survey was distributed to 137 dermatology interest groups across the country. the survey contained 21 multiple choice and free text questions that assessed students’ research experiences and self-assessed competency in key research components. fifty-seven students participated. results: students were most comfortable with creating posters for presenting research, writing an abstract and reviewing charts to gather pertinent data for research projects. students reported a below-average comfort level with data analysis. medical students who participated in more than eight research experiences and those who perform epidemiological research or commentaries have greater confidence in their ability to conduct research. conclusion: experience in research is associated with the ability to conduct research independently, but there is significant variance in the comfortability to perform essential research-related tasks. introduction skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 389 medical student clinical or translational research skills and attitudes toward performing defined research tasks. while objective self-assessment is inherently imperfect, it has been established that objective competence requires a degree of subjective awareness of one’s personal performance and judgement.10 epstein et al proposes a framework that emphasizes integrating external and internal data to assess performance on future learning and self-assessment of skill.11 this study integrates medical student self-assessment of comfortability with externally defined requisite standards of research. our analysis seeks to discover if the current method of undergraduate medical research results in a high degree of self-assessed competence with research skills. an anonymous survey approved by the tulane institutional review board was distributed to 137 dermatology interest group (dig) presidents at dermatology interest group association (diga) affiliated medical schools to be distributed to their members via email listservs. the survey contained 21 questions and consisted of multiple choice and fill-in-the-blank questions that assessed students’ background and research experience. the survey utilized a likert scale to assess students’ comfortability with conducting research. 57 responses were received. responses included students of all years of medical school and 96.4% had participated in research during medical school. first year students represented 30.4% of all survey responses. a majority of students had research experiences outside of the standard medical curriculum with 85.4% of respondents indicating that they were involved in research during undergraduate education and 62.5% participating in research years before attending medical school. 79% of respondents reported having a research mentor in medical school. twentynine percent of students reported participating in dermatology-specific research during medical school. the number and types of research projects varied among respondents. (tables 1 and 2) table 1. number of research projects students participated in during medical school. number of research projects (%) student participation n=45 1-3 n=21 (46.6) 4-7 n=12 (26.7) 8+ n=12 (26.7) table 2. student participation in various categories of research. research project category (%) student participation n=127 case report/case series n=27 (21.3) review article n=17 (13.4) commentary/editorial n=8 (6.3) basic science research study n=13 (10.2) clinical medicine research study n=29 (22.8) educational research study n=16 (12.6) epidemiological research study n=12 (9.5) other n=5 (3.9) comfort levels with different research skills varied when measured on a likert scale. students reported the highest average methods results skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 390 figure 1: graphical representation of students’ responses on a likert scale of 1-5 comfort with creating posters for presenting research (4.22 mean, 0.80 variance). respondents reported considerable comfort with writing an abstract (4.11 mean, 0.85 variance), reviewing charts to gather pertinent data for research projects (4.11 mean, 1.08 variance), and developing a scientific question (4.02 mean, 0.91 variance). students reported the lowest average comfort with analysis of collected data (2.91 mean, 1.68 variance). the most variance in responses was found in comfortability with writing a manuscript for publication (3.53 mean, 1.85 variance) and conducting literature reviews (3.62 mean, 1.75 variance). students were confident in their abilities to conduct research during residency (4.20 mean) with 51.1% of respondents “completely comfortable” in their abilities. a chi square test revealed a significant association between the number of research projects that students participated in and their comfortability with writing an irb protocol, writing a manuscript for publication, and conducting scholarly activity as part of residency in the future (p= <.05). post hoc comparisons revealed that those who participated in >8 research projects were more confident in their ability to conduct research as part of residency than those who had participated in 1-3 projects or 4-7 projects (p=0.02). differences in quality of research yielded varied confidence in ability to conduct research in residency. conducting epidemiological research and writing a commentary/editorial showed a significant association (p=0.02 and 0.04, respectively). writing case reports or review articles showed no association with confidence of conducting research during residency (p= 0.14 and 0.23, respectively). notably, there was an association between year in medical school and comfortability with giving oral presentations and chart review (both p= 0.01). there was no association between 0.8 0.85 1.08 0.91 1.68 1.85 1.75 0 0.2 0.4 0.6 0.8 1 1.2 1.4 1.6 1.8 2 0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 creating posters writing an abstract reviewing charts scientific question analysis of data writing a manuscript literature review li ke rt s ca le 1 -5 medical students' self assessed research skills mean comfort level variance skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 391 completing a research year and any measure of comfort (p= >.05). participation in research is popular among us medical students hoping to match into dermatology residency. students interested in the field recognize the high importance that residency programs place on research participation and publications. the average number of abstracts, presentations, and publications among us seniors who matched into dermatology in 2020 is nineteen.12 however, our survey revealed that students interested in dermatology as a career do not report consistent levels of comfort regarding ability to conduct various forms of research. although self-directed learning is considered a standard for medical school accreditation, independent research is not a requirement.2 instituting research as a standard for accreditation would encourage medical schools to teach the fundamentals of research. there may be potential time and cost restraints associated with implementing formal curriculum interventions. an alternative approach which has been already widely implemented among medical students—mentorship—has been previously associated with increased research productivity, while lack of mentorship has been associated with loss of interest in an academic career.13 while mentorship is highly utilized among our study population, mentorship alone has not closed the gaps uncovered by our study. overall, participation in a larger quantity of research projects yields greater comfortability with writing an irb protocol and writing a manuscript for publication. additionally, case reports have been inversely associated with research productivity during residency, a finding that may be supported by our finding that students who performed case reports had less confidence in research skills.14 future research comparing dermatology applicant comfortability with research compared to that of other similarly competitive specialties could help to establish the pervasiveness of research knowledge gaps and subsequently develop strategies – across specialty and institution – to close those gaps. providing the framework in which medical students can participate in the pre-clinical years of medical school may help build the necessary skills to perform higher quality research in dermatology. the study is limited by use of a non-validated study low response rate and recall bias. because we collected responses from all years of medical school, reported comfort levels may vary based on student-year and curriculum. overall response rate is unknown due to dissemination via listserv. it is possible that students not applying to dermatology were included in the survey. self-selection bias likely occurred and could be associated with respondents completing more or less research than the average dermatology applicant. the results are not generalizable to all medical students. among medical students interested in specializing in dermatology, there are notable discrepancies, as well as some concerning gaps, within students’ research skills. research-focused interventions, such as research participation requirements and/or online educational modules, may be the key to enhancing medical students’ research skills. future studies could examine whether these gaps discourage or encourage participation in research during residency. it discussion conclusion skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 392 is yet to be determined whether high scholarly productivity during medical school is associated with high productivity during residency training. conflict of interest disclosures: none funding: none corresponding author: andrea murina, md, faad tulane university school of medicine 1430 tulane ave., #8036 new orleans, la 70112 email: amurina@tulane.edu references: 1. “functions and structure of a medical school.” lcme, association of american medical colleges and american medical association. lcme.org/publications/. published march 2020. accessed july 2020. 2. laidlaw a, aiton j, struthers j, guild s. developing research skills in medical students: amee guide no. 69. med teach. 2012;34(9):754-771. 3. kanna b, deng c, erickson sn, valerio ja, dimitrov v, soni a. the research rotation: competency-based structured and novel approach to research training of internal medicine residents. bmc med educ. 2006;6. 4. ianni pa, samuels em, eakin bl, perorazio te, ellingrod vl. assessments of research competencies for clinical investigators: a systematic review. eval health prof. december 23, 2019:016327871989639. 5. adkison lr, glaros ag. assessing research competency in a medical school environment. med sci educ. 2012;22(3):139142. 6. sonstein sa, li r, jones ct, silva h, daemen e. moving from compliance to competency: a harmonized core competency framework for the clinical research professional. 7. yoon hb, park dj, shin j-s, ahn c. developing a core competency model for translational medicine curriculum. korean j med educ. 2018;30(3):243-256. 8. dilmore tc, moore dw, bjork z. developing a competency-based educational structure within clinical and translational science. clin transl sci. 2013;6(2):98-102. 9. bordage g. conceptual frameworks to illuminate and magnify. med educ. 2009;43(4):312-319. 10. kruger j, dunning d. unskilled and unaware of it: how difficulties in recognizing one’s own incompetence lead to inflated selfassessments. j pers soc psychol. 1999;77(6):1121-1134. 11. epstein rm, siegel dj, silberman j. selfmonitoring in clinical practice: a challenge for medical educators. j contin educ health prof. 2008;28(1):5-13. 12. characteristics of u.s. md seniors who matched to their preferred specialty in the 2020 main residency match (vol. 2, p. 36). washington, d.c. 2020. national resident matching program. 13. reck sj, stratman ej, vogel c, mukesh bn. assessment of residents’ loss of interest in academic careers and identification of correctable factors. arch dermatol. 2006;142(7):855-858. 14. stephens mr, barbieri js, lipoff jb. predicting future dermatology academic productivity from medical school publications. j am acad dermatol. 2020 aug;83(2):624626. doi: 10.1016/j.jaad.2019.08.076. epub 2019 sep 6. pmid: 31499150 synopsis 90 p ro p o rt io n o f p a ti e n ts a c h ie v in g p a s i 9 0 ( % ) 36 80 70 60 50 40 30 20 10 100 0 weeks 32282420161280 564 52484440 90 p ro p o rt io n o f p a ti e n ts a c h ie v in g p a s i 10 0 ( % ) 36 80 70 60 50 40 30 20 10 100 0 weeks 32282420161280 564 52484440 bimekizumab q4w → q8w (n=161) bimekizumab q4w (n=158) adalimumab (n=159) adalimumab → bimekizumab q4w (n=159) 79.9% 73.6% 84.8% 81.8% 82.6% 88.0% 84.5% 88.0% 86.3% 86.1%* 85.1%* 51.6% 29.6% 72.2% 66.7% 70.2% 70.3% 66.5% 70.3% 69.6% 67.7%* 65.8%* 57.2% 49.7% p ro p o rt io n o f p a ti e n ts a c h ie v in g p a s i 7 5 ( % ) 100 bimekizumab 320 mg q4w (n=319)a adalimumab (n=159) 75 50 25 0 76.5% 31.4% p<0.001 p ro p o rt io n o f p a ti e n ts a c h ie v in g p a s i 9 0 ( % ) 100 bimekizumab 320 mg q4w (n=319)a adalimumab (n=159) 75 50 25 0 86.2% 47.2% p<0.001 p ro p o rt io n o f p a ti e n ts a c h ie v in g i g a 0 /1 ( % ) 100 bimekizumab 320 mg q4w (n=319)a adalimumab (n=159) 75 50 25 0 85.3% 57.2% p<0.001 p ro p o rt io n o f p a ti e n ts a c h ie v in g p a s i 10 0 ( % ) 100 bimekizumab 320 mg q4w (n=319)a adalimumab (n=159) 75 50 25 0 60.8% 23.9% p<0.001 conclusions results demonstrated that bimekizumab was superior to adalimumab over 16 weeks of treatment in terms of the speed, depth and durability of skin clearance in patients with moderate to severe plaque psoriasis. switching from adalimumab to bimekizumab resulted in rapid increases in response rates, comparable to rates in bimekizumab-randomized patients at week 56. no unexpected safety findings were reported in patients who switched from adalimumab to bimekizumab compared with patients who received continuous bimekizumab. bimekizumab 320 mg q8w maintenance dose efficacy was comparable to bimekizumab q4w. the most common teaes were nasopharyngitis, oral candidiasis and upper respiratory tract infections. cases of oral candidiasis were mostly mild or moderate and localized; none led to discontinuation. objectives to compare the efficacy and safety of bimekizumab versus adalimumab in patients with moderate to severe plaque psoriasis. to assess the maintenance of efficacy of bimekizumab dosed every four weeks versus every eight weeks. background • psoriasis is the archetypal th17-driven disease for which both interleukin (il)-17a and il-17f have emerged as pivotal drivers of inflammation.1,2 • bimekizumab is a monoclonal igg1 antibody that selectively inhibits il-17f in addition to il-17a.3,4 • bimekizumab led to substantial clinical improvements in patients with moderate to severe plaque psoriasis in the phase 3 studies be vivid and be ready with no unexpected safety findings.5,6 • here, efficacy and safety of bimekizumab were evaluated versus adalimumab in patients with moderate to severe plaque psoriasis. methods • patients in be sure (nct03412747) were randomized 1:1:1 to bimekizumab 320 mg every four weeks (q4w), bimekizumab 320 mg q4w through week 16 followed by bimekizumab 320 mg every eight weeks (q8w), or adalimumab (dosed 80 mg at week 0 and 40 mg at week 1, then 40 mg q2w until week 23) followed by bimekizumab 320 mg q4w from week 24–56 (figure 1). • co-primary endpoints were 90% improvement from baseline in psoriasis area and severity index (pasi 90) and an investigator’s global assessment score of 0 or 1 (iga 0/1) versus adalimumab at week 16. • secondary endpoints included pasi 75 at week 4, pasi 90 at weeks 24 and 56, and complete skin clearance (pasi 100) at weeks 16 and 24. • treatment-emergent adverse events (teaes) were assessed and coded according to meddra v19.0. • missing data were imputed using non-response imputation (nri). results patient population • 478 patients were randomized to bimekizumab 320 mg q4w (n=158), bimekizumab 320 mg q4w/q8w (n=161), and adalimumab 40 mg q2w/bimekizumab 320 mg q4w (n=159). • baseline characteristics for all randomized patients are shown in table 1. response rates at weeks 4 and 16 • at week 4, a larger proportion of patients treated with bimekizumab reached pasi 75 than those receiving adalimumab (p<0.001; figure 2a). • both co-primary endpoints were achieved at week 16: – significantly more bimekizumab-treated patients achieved pasi 90 and iga 0/1 than those who received adalimumab (p<0.001; figure 2b–c). • pasi 100 was achieved by significantly more patients receiving bimekizumab versus adalimumab at week 16 (p<0.001; figure 2d). response rates through week 56 • at week 24, pasi 90 and pasi 100 response rates remained greater in bimekizumabtreated patients compared with those receiving adalimumab, regardless of bimekizumab dosing regimen (all comparisons: p<0.001; figure 3). • after switching from adalimumab to bimekizumab at week 24, response rates rapidly increased. by week 56, response rates for those who switched were similar to patients initially treated with bimekizumab (figure 3). safety • proportions of teaes, severe teaes, and discontinuations due to teaes were similar between treatment groups (table 2). • there were no unexpected safety findings in patients who switched from adalimumab to bimekizumab in comparison with patients who received continuous bimekizumab treatment (table 2). • in patients receiving bimekizumab, the most common teaes through both weeks 0–24 and weeks 24–56 were nasopharyngitis, oral candidiasis, and upper respiratory tract infection (table 2). – the vast majority of oral candidiasis cases were localized, mild or moderate, superficial infections. there were no discontinuations due to candidiasis infection. • one death occurred during adalimumab treatment (table 2). r.b. warren,1 a. blauvelt,2 j. bagel,3 k.a. papp,4 p. yamauchi,5,6 a. armstrong,7 r. langley,8 v. vanvoorden,9 d. de cuyper,9 l. peterson,10 n. cross,10 k. reich11 bsa: body surface area; dlqi: dermatology life quality index; iga: score of 0 (clear) or 1 (almost clear) with ≥2-category improvement relative to baseline investigator’s global assessment; il: interleukin; imp: investigational medicinal product; itt: intent-to-treat; mace: major adverse cardiovascular event; nmsc: non-melanoma skin cancer; nri: non-responder imputation; pasi 75/90/100: ≥75/90/100% improvement from baseline psoriasis area and severity index; q2w: every 2 weeks; q4w: every 4 weeks; q8w: every 8 weeks; sd: standard deviation; sib: suicidal ideation and behavior; teae: treatment-emergent adverse event; tnf: tumor necrosis factor. figure 1 study design bimekizumab 320 mg q4w n=158 bimekizumab 320 mg q4w/q8w n=161 adalimumab/bimekizumab 320 mg q4w n=159 age (years), mean ± sd 45.3 ± 13.2 44.0 ± 13.5 45.5 ± 14.3 male, n (%) 102 (64.6) 112 (69.6) 114 (71.7) caucasian, n (%) 140 (88.6) 140 (87.0) 141 (88.7) weight (kg), mean ± sd 89.6 ± 21.4 93.2 ± 24.4 90.5 ± 22.1 duration of psoriasis (years), mean ± sd 20.4 ± 13.2 17.3 ± 10.9 16.2 ± 11.9 pasi, mean ± sd 20.5 ± 6.9 19.9 ± 6.1 19.1 ± 5.9 bsa (%), mean ± sd 26.5 ± 15.9 25.2 ± 12.4 25.0 ± 14.4 iga, n (%) 3: moderate 102 (64.6) 111 (68.9) 114 (71.7) 4: severe 56 (35.4) 50 (31.1) 45 (28.3) dlqi total, mean ± sd 11.1 ± 6.5 10.8 ± 6.2 10.5 ± 7.4 any prior systemic therapy, n (%) 112 (70.9) 116 (72.0) 110 (69.2) prior biologic therapy, n (%)a 50 (31.6) 50 (31.1) 53 (33.3) anti-tnf 14 (8.9) 10 (6.2) 14 (8.8) anti-il-17 33 (20.9) 37 (23.0) 35 (22.0) anti-il-12/23 11 (7.0) 9 (5.6) 15 (9.4) anti-il-23 3 (1.9) 2 (1.2) 2 (1.3) institutions: 1dermatology centre, salford royal nhs foundation trust, manchester nihr biomedical research centre, the university of manchester, manchester, uk; 2oregon medical research center, portland, or, usa; 3psoriasis treatment center of central new jersey, east windsor, nj, usa; 4probity medical research and k papp clinical research, waterloo, ontario, canada; 5dermatology institute and skin care center, santa monica, ca, usa; 6division of dermatology, david geffen school of medicine at university of california, los angeles, ca, usa; 7keck school of medicine of usc, dermatology, los angeles, ca, usa; 8dalhousie university, halifax, nova scotia, canada; 9ucb pharma, brussels, belgium; 10ucb pharma, raleigh, nc, usa; 11center for translational research in inflammatory skin diseases, institute for health services research in dermatology and nursing, university medical center hamburg-eppendorf and skinflammation® center, hamburg, germany bimekizumab efficacy and safety versus adalimumab in patients with moderate to severe plaque psoriasis: results from a multicenter, randomized, double-blinded active comparator-controlled phase 3 trial (be sure) presented at winter clinical 2021 virtual congress | january 16–24 references: 1durham l. curr rheumatol reports 2015;17:55; 2fujishima s. arch dermatol res 2010;302:499–505; 3glatt s. br j clin pharmacol 2017;83:991–1001; 4papp ka. j am acad dermatol 2018;79:277–86.e10; 5reich k. aad 2020, nct03370133; 6gordon k. aad 2020, nct03410992. author contributions: substantial contributions to study conception/design, or acquisition/analysis/interpretation of data: rbw, ab, jb, kap, py, aa, rl, vv, ddc, lp, nc, kr; drafting of the publication, or revising it critically for important intellectual content: rbw, ab, jb, kap, py, aa, rl, vv, ddc, lp, nc, kr; final approval of the publication: rbw, ab, jb, kap, py, aa, rl, vv, ddc, lp, nc, kr. author disclosures: rbw: research grants and/or consulting fees from abbvie, almirall, amgen, arena, avillion, boehringer ingelheim, bristol myers squibb, celgene, eli lilly, janssen, leo pharma, novartis, pfizer, sanofi, and ucb pharma; ab: scientific adviser and/or clinical study investigator for abbvie, allergan, almirall, athenex, boehringer ingelheim, bristol myers squibb, dermavant, eli lilly, forte, galderma, incyte, janssen, leo pharma, novartis, pfizer, rapt, regeneron, sanofi genzyme, sun pharma and ucb pharma; paid speaker for abbvie; jb: speaker, investigator and/or consultant for abbvie, celgene, eli lilly, leo pharma, novartis and ortho dermatologics; kap: honoraria and/or grants from abbvie, akros, amgen, arcutis, astellas, baxalta, boehringer ingelheim, bristol myers squibb, canfite, celgene, coherus, dermira, dow pharma, eli lilly, forward pharma, galderma, genentech, gilead, gsk, janssen, kyowa kirin, leo pharma, medimmune, merck (msd), merck-serono, mitsubishi pharma, moberg pharma, novartis, pfizer, prcl research, regeneron, roche, sanofi genzyme, sun pharma, takeda, ucb pharma, and valeant/bausch health; consultant (no compensation) for astrazeneca and meiji seika pharma; py: speaker, investigator, consultant for abbvie, amgen, eli lilly, janssen, novartis, ortho dermatologics, sun pharma and ucb pharma; aa: research investigator and/or consultant for abbvie, bristol myers squibb, dermavant, dermira, eli lilly, janssen, leo pharma, kyowa kirin, modernizing medicine, novartis, ortho dermatologics, regeneron, sanofi, sun pharma and ucb pharma; rl: honoraria from abbvie, amgen, boeringer ingelheim, centocor, eli lilly, janssen, leo pharma, pfizer and valeant/bausch health; vv, lp, ddc, nc: employees of ucb pharma; kr: served as advisor and/or paid speaker for and/or participated in clinical trials sponsored by abbvie, affibody, almirall, amgen, avillion, biogen, boehringer ingelheim, bristol myers squibb, celgene, centocor, covagen, dermira, eli lilly, forward pharma, fresenius medical care, galapagos, gsk, janssen, kyowa kirin, leo pharma, medac, msd, miltenyi biotec, novartis, ocean pharma, pfizer, regeneron, samsung bioepis, sanofi, sun pharma, takeda, ucb pharma, valeant/bausch health, and xenoport. acknowledgements: this study was funded by ucb pharma. we would like to thank the patients and their caregivers in addition to all the investigators and their teams who contributed to this study. the authors acknowledge mylene serna, pharmd, ucb pharma, smyrna, ga, usa and susanne wiegratz, msc, ucb pharma, monheim am rhein, germany for publication coordination; eva cullen, phd, ucb pharma, brussels, belgium for critical review; ruth moulson, mph, costello medical, cambridge, uk for medical writing and editorial assistance; and the costello medical design team for design support. all costs associated with development of this presentation were funded by ucb pharma. previously presented at eadv 2020 virtual congress | october 29–31 aadalimumab was dosed 80 mg at week 0 and 40 mg at week 1, then 40 mg every 2 weeks until week 23. the first dose of bimekizumab in this group was administered at week 24. table 1 baseline characteristics apatients with multiple prior biologics use included in n (%). figure 2 response rates at weeks 4 and 16 (itt, nri) a) pasi 75 at week 4 b) pasi 90 at week 16 c) iga 0/1 at week 16 d) pasi 100 at week 16 adata were pooled from both bimekizumab arms as all patients received the same dose regimen through week 16 (pre-specified). p values for the comparison of treatment groups are based on the cochran-mantel-haenszel test from the general association. figure 3 response rates through week 56 (itt, nri) a) pasi 90 b) pasi 100 p values for the comparison of treatment groups are based on the cochran-mantel-haenszel test from the general association. data shown include all randomized patients. adata for weeks 0–24 are from the full safety set; bdata for weeks 24–56 include only bimekizumab-treated patients; cincludes all patients who received bimekizumab from weeks 0–24, regardless of dosing regimen; d50 year-old male diagnosed with squamous cell carcinoma of the tongue 6 weeks after the start of adalimumab treatment, which led to a fatal outcome 5 months later; eoccurred in >5% of patients in any treatment group through weeks 0–24 or 24–56; fthe majority of liver function test elevations were transient and resolved by end of study; gall fungal infections not classified as candida or tinea were classified as fungal infections nec (not elsewhere classified). table 2 teaes and safety topics of interest aadalimumab was dosed 80 mg at week 0 and 40 mg at week 1, then 40 mg every 2 weeks until week 23. the first dose of bimekizumab in this group was administered at week 24. bimekizumab was superior to adalimumab at week 16 with a similar safety profile to previous studies. weeks 0–24a weeks 24–56b bimekizumab total (n=319) n (%)c adalimumab (n=159) n (%) bimekizumab 320 mg q4w (n=152) n (%) bimekizumab 320 mg q8w (n=149) n (%) adalimumab/bimekizumab 320 mg q4w (n=149) n (%) incidence of teaes any teae 228 (71.5) 111 (69.8) 101 (66.4) 104 (69.8) 111 (74.5) serious teaes 5 (1.6) 5 (3.1) 2 (1.3) 8 (5.4) 9 (6.0) discontinuation due to teaes 9 (2.8) 5 (3.1) 3 (2.0) 2 (1.3) 5 (3.4) drug-related teaes 87 (27.3) 38 (23.9) 40 (26.3) 35 (23.5) 45 (30.2) severe teaes 5 (1.6) 5 (3.1) 5 (3.3) 8 (5.4) 7 (4.7) deaths 0 (0.0) 1 (0.6)d 0 (0.0) 0 (0.0) 0 (0.0) common teaes (>5% patientse) nasopharyngitis 59 (18.5) 38 (23.9) 18 (11.8) 15 (10.1) 20 (13.4) oral candidiasis 34 (10.7) 0 (0.0) 20 (13.2) 13 (8.7) 26 (17.4) upper respiratory tract infection 19 (6.0) 15 (9.4) 8 (5.3) 11 (7.4) 9 (6.0) hypertension 15 (4.7) 13 (8.2) 2 (1.3) 3 (2.0) 3 (2.0) diarrhea 13 (4.1) 4 (2.5) 2 (1.3) 3 (2.0) 2 (1.3) pharyngitis 9 (2.8) 1 (0.6) 3 (2.0) 8 (5.4) 3 (2.0) safety topics of interest inflammatory bowel disease 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) adjudicated sib 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) serious hypersensitivity reaction 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) adjudicated mace 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) all malignancies (inc. nmsc) 4 (1.3) 1 (0.6) 0 (0.0) 2 (1.3) 1 (0.7) neutropenia 2 (0.6) 4 (2.5) 0 (0.0) 0 (0.0) 0 (0.0) hepatic events 7 (2.2) 11 (6.9) 1 (0.7) 3 (2.0) 6 (4.0) liver function analysesf 7 (2.2) 11 (6.9) 1 (0.7) 2 (1.3) 6 (4.0) fungal infectionsg 50 (15.7) 1 (0.6) 30 (19.7) 22 (14.8) 35 (23.5) candida infections 38 (11.9) 0 (0.0) 22 (14.5) 14 (9.4) 27 (18.1) tinea infections 11 (3.4) 1 (0.6) 2 (1.3) 6 (4.0) 1 (0.7) serious infections 1 (0.3) 1 (0.6) 1 (0.7) 2 (1.3) 4 (2.7) screening initial treatment period maintenance periodscreening patient inclusion criteria ≥18 years of age plaque psoriasis with ≥6 months’ symptom duration moderate to severe disease: pasi ≥12, bsa a�ected by psoriasis ≥10%   n=478 1:1:1 randomization open-label extension study: be bright (nct03598790) 20 weeks after last dose of imp: safety follow-up week 16 week 24baseline 2–5 weeks co-primary endpoints: pasi 90 and iga 0/1 bimekizumab 320 mg q4w bimekizumab 320 mg q4w adalimumab 40 mg q2wa bimekizumab 320 mg q4w bimekizumab 320 mg q8w week 56 dosing visits n=158 n=161 n=159  bimekizumab 320 mg q4w (n=319) adalimumab 40 mg q2wa (n=159) bimekizumab 320 mg q4w (n=319) adalimumab 40 mg q2wa (n=159) pasi 90 at week 16 iga 0/1 at week 16 primary endpoints 86.2% 47.2% 85.3% 57.2% n=158 n=161 n=159 bimekizumab 320 mg q4w bimekizumab 320 mg q4w bimekizumab 320 mg q4w bimekizumab 320 mg q8w adalimumab 40 mg q2wa wk 16 wk 24 treatment groups *p value versus adalimumab <0.001 *p value versus adalimumab <0.001 skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 423 brief articles a case of widespread cutaneous metastases from esophageal adenocarcinoma caroline b. crain, bs1, adam v. nguyen, md2, janice m. wilson, md2, michael g. wilkerson, md2 1school of medicine, the university of texas medical branch, galveston, texas 2department of dermatology, the university of texas medical branch, galveston, texas cutaneous metastases from internal malignancies are very rare and occur in only 0.5 to 9% of cases.1,2 it often indicates a poor prognosis, with an average survival time of about 7.5 months.3 metastasis to the skin most commonly originates from lung, breast, and colorectal cancers, and only a few cases of cutaneous metastases from esophageal cancer have been reported.2,4,5 here, we present the case of a 61-year-old patient with recently diagnosed esophageal adenocarcinoma and widespread cutaneous metastases. a 61-year-old male with past medical history of gastroesophageal reflux disease, hepatitis c, and hypothyroidism was originally admitted for progressive dysphagia and significant weight loss. after an endoscopic biopsy, he was diagnosed with poorly differentiated esophageal adenocarcinoma. dermatology was consulted for the evaluation of multiple skin nodules which were concerning for cutaneous metastases. oncology wanted to determine whether the metastases were from the patient’s esophageal cancer or from a different primary source, in order to better formulate their treatment plan. the patient reported recent enlargement of some of the lesions, with associated pain. he denied any pruritus or bleeding associated with the nodules. on physical examination, there were firm, indurated, slightly mobile subcutaneous nodules present on the scalp, left cheek, back, abdomen, hands, and right thigh cutaneous metastases from internal malignancies are very rare, and only a few cases from esophageal cancer have been reported. we describe the case of a 61-year-old patient with recently diagnosed esophageal adenocarcinoma who presented with multiple skin nodules. immunohistochemical analysis of the nodules matched the immunohistochemical profile of the patient’s previous esophageal biopsy specimen, confirming the diagnosis of cutaneous metastases. this case highlights the importance of including cutaneous metastases in the differential diagnosis of any suspicious lesion in patients with a history of internal malignancy. introduction abstract case report skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 424 (figure 1). a punch biopsy was taken from a nodule on the left anterior shoulder and from a nodule on the left flank. histopathologic analysis revealed a tumor in the deep dermis composed of atypical epithelial cells with focal gland formation (figure 2). immunohistochemical analysis revealed the tumor to be ck7+ (figure 3), ck20-, and p40and to express her2 with 2+ positivity; this matched the immunohistochemical profile of the patient’s previous esophageal biopsy specimen. these findings were consistent with cutaneous metastases from the patient’s esophageal adenocarcinoma. figure 1. indurated subcutaneous nodules present on the patient’s left flank. figure 2. punch biopsy, h&e, 200x: rudimentary gland formation, pleomorphism, nuclear hyperchromatism, and frequent mitotic figures. figure 3. punch biopsy, ck7, 100x: diffuse positivity with ck7. immunohistochemical staining for ck20 and p40 were negative. her2 staining was 2+. the incidence of cutaneous metastases from esophageal adenocarcinoma is about 1% and typically involves the overlying skin of the primary tumor or the scalp.6 the clinical manifestations of cutaneous metastasis vary widely, but it usually presents as an asymptomatic, firm nodule.3 cutaneous metastases represent advanced progression of the primary malignancy, and removal of these lesions does not have any impact on the survival rate of the patient.5 we present an unusual case as our patient was relatively functional at the time of discussion skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 425 presentation with multiple areas of metastasis to the skin. worldwide, squamous cell carcinoma is the most common type of esophageal cancer.7 however, the incidence of esophageal adenocarcinoma in developed countries has increased dramatically since the 1970s, and this subtype now predominates in the united states.7 the pathogenesis of esophageal adenocarcinoma is not fully understood, but barrett’s esophagus is a well-known risk factor.8 barrett’s esophagus results from acid biliary reflux from the stomach into the esophagus, leading to the replacement of native squamous epithelium with columnar epithelium. the combination of esophageal inflammation and somatic genomic instability promote carcinogenesis, and over time, can lead to the development of esophageal adenocarcinoma.9 one possible genomic alteration can involve the amplification and overexpression of the human epidermal growth factor 2 (her2) oncogene. her2 is an established target in esophageal and gastric cancers as it regulates cell growth, survival, differentiation, and migration.10 the status of her2 is important to assess in patients with esophageal adenocarcinoma as it can help guide chemotherapy with the use of targeted agents like trastuzumab. immunohistochemical staining provides diagnostic guidance and helps distinguish between adenocarcinoma and squamous cell carcinoma.11 more specifically, the staining pattern for cytokeratin 7 (ck7) and cytokeratin 20 (ck20) can aid in the identification of esophageal adenocarcinoma. ck20 is typically expressed in tumors of the lower gastrointestinal tract, while ck7 is expressed in barrett’s esophagus and esophageal adenocarcinoma.12 ormsby et al. found that barrett’s-related adenocarcinomas consistently revealed a ck7+/ck20pattern, whereas gastric adenocarcinomas demonstrated much more variation in the ck7/20 immunophenotype.13 the ck7+/ck20pattern was present in both the cutaneous and esophageal specimens from our patient, supporting the diagnosis of cutaneous metastasis from esophageal adenocarcinoma. also, p40 is a marker of squamous cell carcinoma and helps distinguish from adenocarcinoma.11 it was negative in both the cutaneous and esophageal specimens, which further supported the diagnosis of cutaneous metastasis from esophageal adenocarcinoma. in cases of either adenocarcinoma or squamous cell carcinoma that have become advanced, typical immunohistochemical markers may be lost, and sometimes only a diagnosis of poorly-differentiated carcinoma can be made.11 this case highlights the importance of including cutaneous metastases in the differential diagnosis of any suspicious lesion in patients with a history of internal malignancy. these lesions should be biopsied and evaluated histopathologically. it is imperative to determine the primary source as it can alter the direction of treatment as exemplified in the case of our patient. despite the rare incidence of cutaneous metastases, patients with esophageal malignancies and growing or changing skin lesions should follow up with dermatology. skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 426 conflict of interest disclosures: none funding: none corresponding author: adam nguyen, md university of texas medical branch department of dermatology galveston, tx email: adnguyen@utmb.edu references: 1. lookingbill dp, spangler n, helm kf. cutaneous metastases in patients with metastatic carcinoma: a retrospective study of 4020 patients. j am acad dermatol. 1993;29((2 pt 1)):228-236. 2. park jm, kim ds, oh sh, kwon ys, lee kh. a case of esophageal adenocarcinoma metastasized to the scalp. ann dermatol. 2009;21(2):164–167f. 3. saeed s, keehn ca, morgan mb. cutaneous metastases: a clinical, pathological and immunohistochemical appraisal. j cutan pathol. 1994;31:419–430. 4. adyanthaya r. multiple cutaneous metastases from esophageal adenocarcinoma. j gastrointest cancer. 2008;39(1-4):22-25. 5. triantafyllou, stamatina et al. cutaneous metastases from esophageal adenocarcinoma. int surg. 100(3):558-561. 6. moreno racionero, a. b. de andres, m. bedate nunez et al. unusual relationship between skin lesions and esophageal cancer: a case report and review of literature. zeitschrift für gastroenterologie. 2015;53(2):115-119. 7. thrift ap. the epidemic of oesophageal carcinoma: where are we now? cancer epidemiol. 2016;41:88. 8. quante, michael, graham, trevor a, and jansen, marnix. insights into the pathophysiology of esophageal adenocarcinoma. gastroenterology. 2018;154(2):406-420. 9. li, xiaohong et al. temporal and spatial evolution of somatic chromosomal alterations: a case-cohort study of barrett’s esophagus.” cancer prev res. 2014;7(1):114-127. 10. yoon, hh et al. her-2/neu gene amplification in relation to expression of her2 and her3 proteins in patients with esophageal adenocarcinoma. cancer. 2014;120(3):415424. 11. selves j, long-mira e, mathieu mc, et al. immunohistochemistry for diagnosis of metastatic carcinomas of unknown primary site. cancers (basel). 2018;10:e108. 12. roh, ellen k, nord, roland, and jukic, drazen m. scalp metastasis from esophageal adenocarcinoma. cutis. 77(2):106-108. 13. ormsby ah, goldblum jr, rice tw, et al. cytokeratin subsets can reliably distinguish barrett’s esophagus from intestinal metaplasia of the stomach. hum pathol. 1999;30:288-94. mailto:adnguyen@utmb.edu skin july 2021 1200 proof skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 406 brief article blastomycosis infection in the setting of immunosuppression with concurrent methotrexate and adalimumab for treatment of psoriasis sebastian otto-meyer, ba1, skylar nahi, ba1, ahmad amin, md1 1department of dermatology, northwestern university feinberg school of medicine, chicago, il blastomycosis is a dimorphic fungi that can infect both immunocompetent and immunocompromised individuals1. it is endemic to the ohio/mississippi rivers area and the great lakes, where patients may inhale spores or fragments that transform to yeast in the lungs, resulting in pneumonia and flu-like symptoms, with occasional involvement of the skin and other organs. endemic fungal infections, such as histoplasmosis, blastomycosis, and coccidioidomycosis, have been frequently reported in patients taking tnf-α inhibitors, including adalimumab. although sixteen cases of blastomycosis associated with tnf-α inhibitor use have been reported to the fda adverse event reporting system, no systemic cases have been described with a detailed clinical course in the literature2. we present a case of pulmonary blastomycosis associated with adalimumab use in a patient with psoriasis. a 71-year-old man with a history of psoriasis and psoriatic arthritis on adalimumab and methotrexate presented with two weeks of fatigue, decreased appetite, and night sweats. the patient’s psoriasis had been well-managed on adalimumab for seven to eight years (40 mg/0.8 ml pen every other week) with a recent addition of 15 mg methotrexate (mtx) weekly targeted at the psoriatic arthritis. extensive work-up upon admission revealed enlarged perihilar and mediastinal lymph nodes on chest ct as well as positive blastomycosis and histoplasmosis urine antigens. the blastomycosis was considered to be the true positive, with abstract blastomycosis is a dimorphic fungi endemic to the ohio/mississippi rivers and the great lakes that can infect immunocompetent and immunosuppressed individuals. systemic fungal infections, such as histoplasmosis or blastomycosis, have often been reported in patients taking tnf-α inhibitors such as adalimumab. however, blastomycosis is significantly less common than histoplasmosis and no cases have been described in the literature. we report a case of systemic blastomycosis associated with adalimumab and methotrexate use for psoriasis and psoriatic arthritis treatment that required extensive treatment and discontinuation of both medications. to our knowledge, this is the first case of systemic blastomycosis associated with adalimumab and methotrexate treatment for psoriasis to be described in the literature. introduction case report skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 407 histoplasmosis antigen positivity a likely cross-reaction. diagnosis of disseminated blastomycoses was made. no skin findings concerning for blastomycosis were found. treatment was initiated with amphotericin b. however, rapidly worsening bilirubin and serum creatinine necessitated discontinuation. oral itraconazole was started, but an elevation in liver enzymes resulted in a switch to voriconazole. as his symptoms resolved and labs normalized, he was discharged on a 12-month course of voriconazole. adalimumab and methotrexate were discontinued upon initial admission and not restarted upon discharge. outpatient bronchoscopy confirmed blastomycosis in pulmonary nodules, but the patient continued to do well on voriconazole. dermatologic follow-up was unremarkable with no significant recurrence of psoriasis for 1.5 years. mild psoriatic outbreaks were managed with topicals, including clobetasol 0.05% to body and hydrocortisone 2.5% to face. however, psoriasis worsened after 2 years off adalimumab despite consistent topical use, with extensive pruritic outbreaks on the legs, back, and trunk. at this point, a targeted il-23 inhibitor (tildrakizumab-asmn) was started with improvement. to our knowledge, this is the first descriptive case report of blastomycosis associated with adalimumab use published in the literature. although sixteen cases are reported (including disseminated and cutaneous blastomycosis) within the fda adverse event reporting system (faers), the clinical details have not been established. although methotrexate has been associated with blastomycosis in faers, the relatively small dose of methotrexate was unlikely to be the primary contributor. here, we show that despite tnf—α inhibitor use along with methotrexate, the course of blastomycosis was relatively mild and able to be treated on an extended course of voriconazole. however, as 6 cases reported to the fda resulted in death, this is clearly not always the case. we also demonstrate how his adalimumab was able to be safely stopped with minimal additional psoriasis for over a year, a fact that should be helpful guidance to dermatologists questioning the relevance of restarting a tnf—α inhibitor after infection. this case raises several interesting concerns in the face of chronic tnf—α use. a metaanalysis of rcts in patients with rheumatoid arthritis found that the use of biological dmards did not significantly increase the risk of invasive and superficial fungal infections (or 1.31; 95% ci 0.46–3.72) or invasive fungal infections (or 2.85; 95% ci 0.68–11.91).3 as such, a dmard such as methotrexate (mtx) is less likely to be the sole etiology of the susceptibility to blastomycosis infection. further, post licensure surveillance of adverse effects has associated the use of methotrexate concurrently with a tnfα inhibitor (infliximab) with a higher risk for developing an endemic fungal infection of histoplasmosis4. in the literature today, adverse event studies and case series demonstrate an association between patients on a tnfα inhibitor and mtx and increased susceptibility to dimorphic fungi infection. this case adds to the understanding of the these infections, demonstrating the details of an association between co-administration of a tnfα inhibitor and mtx, with subsequent opportunistic infection by blastomycosis5. this case report complements the incidence of histoplasmosis observed with tnf-α inhibitor therapy in the literature. it further supports the importance of screening all patients for risk factors prior to starting discussion skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 408 adalimumab and mtx therapy, and then annually. this includes questioning patients about travel to endemic regions and participation in activities that may increase risk of exposure6. although there are no formal recommendations on screening strategies in high-risk patients, these patients may warrant closer monitoring. indeed, this case illustrates that any patient experiencing concerning symptoms, such as prolonged fatigue, weight loss, or night sweats, should be carefully assessed if they are taking a tnf-α inhibitor. a consensus document on the safety of targeted and biological therapies demonstrated that no benefit is expected from the use of antibacterial, antipneumocystis or antifungal prophylaxis in a patient cohort on anti-tnf-α therapy7. however, after infection, rigorous anti-fungal regimes are essential, and may be justified for extended periods. in the case of the patient in this discussion, increase in baseline psoriatic activity may increase interest in restarting his adalimumab regimen. a history of a dimorphic fungal infection may justify consideration of fluconazole "maintenance.” this can be recommended in those patients who desire to restart a tnf-α antagonist such as adalimumab, a recommendation guided by studies on fungal infection relapse in immunosuppressed patients who discontinued fungal prophylaxis8,9. if chronic maintenance therapy is not implemented, urine antigen screening at 3-month intervals may be performed to look for recurrence. alternatively, as in this case, a new biologic, such as an il-17 or il-23 inhibitor, can be started. while these also may impair antifungal immunologic defenses, a recent review found no reports of invasive fungal disease following treatment of psoriasis or other inflammatory conditions with il-17 or il-23 inhibitors10. conflict of interest disclosures: none funding: none corresponding author: ahmad amin, md department of dermatology feinberg school of medicine 111 w washington st ste 1801 chicago, il 60602 email: ahmad.amin@nm.org references: 1. mcbride ja, gauthier gm, klein bs. clinical manifestations and treatment of blastomycosis. clin chest med. 2017;38(3):435-449. 2. fda adverse events reporting system (faers) public dashboard. accessed january 7, 2021. 3. kourbeti is, ziakas pd, mylonakis e. biologic therapies in rheumatoid arthritis and the risk of opportunistic infections: a meta-analysis. clinical infectious diseases. 2014;58(12):16491657. 4. lee jh, slifman nr, gershon sk, et al. lifethreatening histoplasmosis complicating immunotherapy with tumor necrosis factor alpha antagonists infliximab and etanercept. arthritis rheum. 2002;46(10):2565-2570. 5. crum nf, lederman er, wallace mr. infections associated with tumor necrosis factor-α antagonists. medicine. 2005;84(5):291302. 6. toussi ss, pan n, walters hm, walsh tj. infections in children and adolescents with juvenile idiopathic arthritis and inflammatory bowel disease treated with tumor necrosis factor-α inhibitors: systematic review of the literature. clin infect dis. 2013;57(9):1318-1330. 7. baddley jw, cantini f, goletti d, et al. escmid study group for infections in compromised hosts (esgich) consensus document on the safety of targeted and biological therapies: an infectious diseases perspective (soluble immune effector molecules [i]: anti-tumor necrosis factor-α agents). clin microbiol infect. 2018;24 suppl 2:s10-s20. 8. mathew g, smedema m, wheat lj, goldman m. relapse of coccidioidomycosis despite immune reconstitution after fluconazole conclusion skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 409 secondary prophylaxis in a patient with aids. mycoses. 2003;46(1-2):42-44. 9. wood kl, hage ca, knox ks, et al. histoplasmosis after treatment with anti-tumor necrosis factor-alpha therapy. am j respir crit care med. 2003;167(9):1279-1282. 10. lee mp, wu kk, lee eb, wu jj. risk for deep fungal infections during il-17 and il-23 inhibitor therapy for psoriasis. cutis. 2020;106(4):199205. skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 685 brief article multinucleate cell angiohistiocytoma: a case report and unique treatment consideration maria karim, ba1, marlyn wu, do2, adriana ros, do3 1 hackensack university medical center, hackensack, nj 2 hackensack meridian health palisades medical center, north bergen, nj 3 dermatology institute & laser center, clifton, nj multinucleate cell angiohistiocytoma (mcah) is a benign, yet exceedingly rare vascular and fibrohistiocytic proliferation. mcah is characterized by multiple red brown or violaceous papules measuring 215 mm in diameter typically occurring on the face and distal extremities, most commonly in middleaged and elderly females.1 lesions are typically characterized by multinucleated giant cells with angulated cytoplasm, dilated capillaries and small vessel proliferation in the papillary to mid dermis, and thickened collagen bundles with fibrous stroma.2 the lesions are typically asymptomatic, but may be associated with mild pruritus, and are commonly cosmetically displeasing to patients.3 previous reports have demonstrated success in treating mcah with fractional ablative co2 laser, argon laser, pulsed dye laser, intense pulsed light, and ktp lasers.2,4,5,6,7 the scarcity of reported cases abstract introduction: multinucleate cell angiohistiocytoma (mcah) is a benign, yet exceedingly rare vascular and fibrohistiocytic proliferation. the lesions are typically asymptomatic and are commonly cosmetically displeasing to patients. 1 previous reports have demonstrated success in treating mcah with fractional ablative co2 laser, argon laser, pulsed dye laser, and ktp lasers. 3 the scarcity of reported cases may suggest that the lesion is commonly misdiagnosed, and we report this case to highlight the characteristic features of mcah with successful treatment with neodymium yag laser. case presentation: a 64-yearold female presented to our clinic with a 1month history of multiple erythematous to violaceous lesions on her bilateral hands. the lesions were asymptomatic, but cosmetically displeasing for the patient. past medical history and family history was noncontributory. examination revealed several 2-6 mm wellcircumscribed, erythematous, indurated smooth papules on the bilateral dorsal and in the second web space of the left hand. shave biopsy of the lesions were consistent with mcah. she was initially treated with topical steroids twice daily for 2 weeks, with no improvement. the patient received 3 treatments with neodymium yag, 4 weeks apart. this treatment was discontinued after 3 sessions due to the dramatic visible improvements in regards to induration and discoloration of the lesions. conclusion: mcah is an extremely uncommon lesion, diagnosis is made on the basis of clinical examination, histopathologic and immunohistochemical analysis of the lesions. this case illustrates diagnosis and successful treatment of mcah with neodymium yag and offers a unique treatment consideration for patients. introduction skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 686 may suggest that the lesion is commonly misdiagnosed. we report this case to highlight the characteristic features of mcah, and to report a unique case of successful treatment of mcah with neodymium (nd) yag laser. a 64-yearold female presented to our clinic with a 1month history of multiple erythematous to violaceous lesions on her bilateral hands. the lesions were asymptomatic, but cosmetically displeasing for the patient. medical history was significant for hypercholesterolemia and hyperthyroidism. family history of similar lesions was noncontributory. a routine investigation including blood count and metabolic profile did not reveal any underlying abnormality. physical examination revealed several discrete 2-6 mm, wellcircumscribed, erythematous, indurated smooth papules on the dorsal hands bilaterally, and in the second web space of the left hand (fig 1). figure 1. multiple, wellcircumscribed, erythematous, indurated smooth papules measuring 2-6 mm each, on the dorsal hands bilaterally, and in the second web space of the left hand the differential diagnosis included gottron papules, papular granuloma annulare and lichen planus. shave biopsy of the lesions revealed an increased number of dilated blood vessels, multinucleated cells, and thickened collagen bundles. these findings are consistent with mcah (fig 2). she was initially treated with topical betamethasone dipropionate 0.05% cream twice daily for 2 weeks previously, with no improvement in the gross appearance of the lesions. figure 2. the pathologic examination revealed an increased number of dilated blood vessels, multinucleated cells, and thickened collagen bundles. these findings are consistent with mcah (hematoxylin-eosin stain). the patient received treatment with nd: yag laser (wavelength 1064 nd yag, fluence: level 6 (6mm), level 8(2mm), pulse duration: 6 microsecs, spot size: 6mm, 2mm), each session 4 weeks apart. after 3 sessions, the patient had dramatic visible improvement in the induration and discoloration of the lesions. (fig 3) multinucleate cell angiohistiocytoma is an extremely uncommon clinical entity, with relatively few cases reported since it was first described in 1985 by smith and wilson jones.8 the clinical presentation of mcah involves one or several firm, erythematous case report discussion skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 687 to violaceous domeshaped papules with a flat top, usually presenting on the distal figure 3. post 3 sessions of neodymium yag laser treatments. extremities. the lesions tend to be well demarcated and follow a random, linear, or annular distribution pattern. the lesions tend to follow a slowly progressive course, and rarely remit spontaneously.9 diagnosis is made on the basis of clinical examination and histopathologic and immunohistochemical analysis of the lesions. histopathologically, characteristic findings include basophilic, stellate multinucleated cells, small vessel inflammation and proliferation, dermal fibrosis, and sparse lymphohistiocytic infiltrates. the multinucleate cells characteristically have angulated cytoplasms, with several hyperchromatic nuclei arranged around the periphery of the cells, comparable to the multinucleated cells seen in dermatofibroma.9 immunohistochemical staining has been found to be positive for vimentin, cd34, cd31, and factor viiirelated antigen, with some cases reported to have cd68 expression of multinucleate cells depending on varying maturation or degenerative stages of the cells.9 this staining pattern suggests a fibroblastic origin preceding the multinucleate cells, rather than a monocytic one due to the lack of expression of monocyte markers. several hypotheses have been proposed to contribute to the progression of the lesions, though the exact pathogenic mechanism has yet to be elucidated. the role of mast cell degranulation, and more specifically, the release of interleukin4, have been implicated in the pathogenesis of the disease.10 cesinaro et al reported a potential link to female hormones, elucidating the relationship between lesions expressing estrogen receptor alpha on their interstitial and multinucleate cells, and the female predominance associated with the disease.11 mcah tends to have a slowly progressive and indolent, yet benign course. to date, extracutaneous symptoms and malignant transformation have not been reported, while spontaneous regression has been.10 these findings together suggest a reactive inflammatory, rather than neoplastic, process. 3 accordingly, it is important to biopsy the lesions to correctly diagnose and appropriately treat patients. it is crucial to recognize that mcah may present as single or multiple papules, with a distribution that may imitate that of an inflammatory process.1 although there is no consensus on the optimal treatment regimen, management of the lesions typically begins with topical or intralesional corticosteroids.2 successful treatment has been reported using surgical excision, cryotherapy, pulseddye or argon laser, intense pulsed light, or carbon dioxide laser.2 further studies are needed to conclusion skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 688 compare the efficacy of various treatment modalities in patients with mcah. conflict of interest disclosures: none funding: none corresponding author: marlyn wu, do 7650 river road suite 120 north bergen, nj 07047 phone: 347-669-4034 email: drwuderm@gmail.com references: 1. frew j. w. (2015). multinucleate cell angiohistiocytoma: clinicopathological correlation of 142 cases with insights into etiology and pathogenesis. the american journal of dermatopathology, 37(3), 222– 228. 2. tuchayi, s. m., garibyan, l., & lee, k. c. (2019). successful treatment of multinucleate cell angiohistiocytoma with fractionated ablative co2 laser. jaad case reports, 5(4), 297-299. 3. wang, m., abdul‐fattah, b., wang, c., zhao, y., qu, x., al‐muriesh, m., ... & chen, s. (2017). generalized multinucleate cell angiohistiocytoma: case report and literature review. journal of cutaneous pathology, 44(2), 125-134. 4. edgerton, b., ladha, m. a., hunter, c., devani, a. r., & prajapati, v. h. (2019). successful treatment of multinucleate cell angiohistiocytoma in an adult male patient with potassium-titanyl-phosphate laser in combination with intralesional corticosteroids. jaad case reports, 5(10), 880-882. 5. kopera, d., smolle, j., & kerl, h. (1995). multinucleate cell angiohistiocytoma: treatment with argon laser. the british journal of dermatology, 133(2), 308–310. 6. richer, v., & lui, h. (2016). facial multinucleate cell angiohistiocytoma: longterm remission with 585 nm pulsed dye laser. clinical and experimental dermatology, 41(3), 312–313. 7. fernández-jorge, b., del pozo, j., garcíasilva, j., barja, j. m., yebra-pimentel, m. t., & fonseca, e. (2009). multinucleate cell angiohistiocytoma: treatment using intense pulsed light. dermatologic surgery : official publication for american society for dermatologic surgery [et al.], 35(7), 1141– 1143. 8. smith, n.p. and jones, e.w. (1985), multinucleate cell angiohistiocytoma—a new entity. british journal of dermatology, 113: 15-15. 9. applebaum, d. s., shuja, f., hicks, l., cockerell, c., & hsu, s. (2014). multinucleate cell angiohistiocytoma: a case report and review of the literature. dermatology online journal, 20(5). 10. roy, s. f., dong, d., myung, p., & mcniff, j. m. (2019). multinucleate cell angiohistiocytoma: a clinicopathologic study of 62 cases and proposed diagnostic criteria. journal of cutaneous pathology, 46(8), 563-569. 11. cesinaro, a. m., roncati, l., & maiorana, a. (2010). estrogen receptor alpha overexpression in multinucleate cell angiohistiocytoma: new insights into the pathogenesis of a reactive process. the american journal of dermatopathology, 32(7), 655–659. mailto:drwuderm@gmail.com skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 146 rising derm stars® tackling lower extremity surgical site infection in dermatologic surgery neera r. nathan, md, mshs1, su luo, md and suzanne m. olbricht, md 1department of dermatology, harvard medical school, boston, ma background/objectives: surgical site infection (ssi) leads to excess healthcare costs and may contribute to increasing bacterial resistance rates due to use of antibiotics. ssi is the most common adverse event following dermatologic surgery,1 especially when the procedure is performed on the lower extremity.2 there is a dearth of information about factors that contribute to ssi following lower extremity dermatologic surgery, and further, investigations about prevention. methods and results: in the first part of this study, we evaluated ssi rates following excision or mohs surgery on the lower extremity using patient demographics, tumor characteristics, surgical approach and pathogenic organisms. using a retrospective review of cases from the lahey clinic department of dermatology over a 15-month period, we demonstrated an ssi rate of 6.3% (21/332 cases). of sites evaluated on the lower extremity, the lower leg was the most commonly infected area (70% of all cases, figure 1). the predominant organism demonstrated on culture was staphylococcus aureus, contained in 16 out of 21 cases; of which, two were methicillinresistant staphylococcus aureus. a complete or partial purse-string repair closure was significantly associated with increased ssi rate (p<.0001). ten of the infected cases (47%) were repaired with a purse-string closure while only 7.5% of all cases utilized this repair. advanced age, location of the tumor, defect size, type of suture used, and duration of surgery did not appear to be significantly related to ssis and neither, reassuringly, did trainee participation. given the predilection for ssi on the lower leg, we performed a prospective review of calamine and zinc oxide impregnated gauze wrap (unna boot) applied post-procedure to see if this could reduce infection rates. an additional 410 cases over an 18-month period from our institution were analyzed. unna boot was applied post-procedure in 70 cases on the lower extremity (table 1). five of the 70 cases were complicated by definitive infection (7.1%), compared to 20 (5.9%) cases that used standard dressings and home wound care (p=0.7829). conclusion: while a purse-string closure is a good option to reduce the surgical defect area and time to heal lower extremity wounds, our study suggests that there is a significantly increased ssi rate with this technique. one putative explanation is that a purse-string closure without excised dogears leads to greater tension and potential pressure necrosis in an area of already compromised blood supply. there was no significant difference between the rate of infection with and without unna boot applied post-procedure. it is possible that selection skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 147 for patients with an increased risk of infection, including patients with venous stasis or limited ability to perform home wound care, was enriched in the unna boot cohort. further investigation is necessary to identify interventions that may help reduce the high infection rate following dermatologic surgery on the lower leg. the control of infections following dermatologic surgery has implications not only for our field, but for the health care system at-large. thorough investigation of this topic will exemplify dermatology as a leader in preventing complications and good antibiotic stewardship. figure 1. site-specific infection rate following lower extremity dermatologic surgery. table 1. lower extremity dermatologic surgery infection rate with unna boot use. with unna boot without unna boot n rate of infection % n rate of infection % total number of exc or mohs 70 34 0 total suspected infections 10 14.30 40 11.80 no culture 4 17 negative culture 1 1 total cultureproven infections 5 22 distinct events 5 7.10 20 * 5.90 *2 patients had 2 sites each excised on the ipsilateral leg and subsequently infected following the same visit. references: 1. o’neill, jl, yee, ys, solomon, ja, patel, n, shutty, b, davis, sa, robins, dn, williford, pm, feldman, sr, pearce, dj. quantifying and characterizing adverse events in dermatologic surgery. dermatol surg 2013. 39(6): 872-878. 2. dixon, aj, dixon, mp, askew, da, wilkinson, d. prospective study of wound infections in dermatologic surgery in absence of prophylactic antibiotics. dermatol surg 2006. (32)6: 819-826. skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 697 brief article primary cutaneous plasmacytoma treated with palliative radiotherapy: a case report and literature review suzanne alkul, md1, yuangao liu, bs2, scott whipple, pa-c3,gordana verstovsek, md4, soo jung kim md, phd1 1 department of dermatology, baylor college of medicine, houston, tx 2 baylor college of medicine, houston, tx 3 department of dermatology, michael e. debakey vamc, houston, tx 4 department of pathology and immunology, baylor college of medicine, houston, tx primary extramedullary plasmacytoma (emp) is a rare plasma cell neoplasm. about 80% of emps occur in the head and neck regions, gastrointestinal tract, and the lymph nodes1. only about 2-4% emps present in the skin or subcutaneous tissue and are referred to as primary cutaneous plasmacytomas (pcp)1. they are, by definition, isolated neoplasms and occur without underlying multiple myeloma (mm). we present a case of a pcp presenting as enlarging, erythematous nodules cared for by a wound care team before being referred to dermatology for assistance in diagnosis. a 78-year-old man with a past medical history of congestive heart failure and endstage renal disease on hemodialysis was referred to dermatology for a three-year history of non-healing, enlarging, bleeding lesions on the right lower extremity. he denied constitutional symptoms including abstract introduction: primary cutaneous plasmacytomas (pcp) are very rare plasma cell neoplasms present in the skin or subcutaneous tissue without underlying multiple myeloma (mm). case report: a 78-year-old man was referred to dermatology by wound care for a three-year history of non-healing, enlarging, bleeding lesions on the right lower extremity. examination revealed multiple firm, tender, slightly mobile erythematous to violaceous nodules ranging from 1 to 5 cm in size, some with erosion and heme crusting. histopathologic analysis of skin biopsies showed an expansile nodular plasmocytic infiltrate in the dermis. a diagnosis of pcp was made based on clinical and histopathological features. our patient underwent palliative radiation and responded to the therapy with decrease in size of all lesions. conclusion: we present a case of pcp presenting as multiple erythematous nodules as opposed to a solitary neoplasm, which likely represents a spectrum of variation of one tumor. to diagnose pcp, patients should not meet criteria for mm. all patients with new solitary plasmacytoma should be evaluated with skeletal survey or computed tomography, mri, and pet/ct to rule out additional lesions. pcps are usually indolent but 10% to 30% progress to mm within 10 years. radiation therapy is considered the standard treatment, and additional clinical trials are underway to test the role of adjuvant chemotherapies. introduction case report skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 698 fatigue, weight loss, night sweats, fever, or chills. the nodules were previously treated by the wound care team with zinc oxide, silver impregnated gel, and petrolatum impregnated non-adherent dressings. examination revealed multiple firm, tender, slightly mobile erythematous to violaceous nodules ranging from 1 to 5 cm in size, some with erosion and heme crusting (figure 1). additionally, the lower legs were noted to be hyperpigmented with 2+ pitting edema, consistent with chronic stasis dermatitis. he had no inguinal lymphadenopathy. histopathologic analysis of skin biopsies showed an expansile nodular plasmocytic infiltrate in the dermis. by immunohistochemistry (ihc), lesion cells were positive for cd138 (strong, diffuse), cd45 (partial), cd10 (partial), and epithelial membrane antigen (partial) (figure 2). the following markers were negative: cd20, pax5, cd30, cyclin d1, eber-ish, anaplastic lymphoma kinase-1, cytokeratin (ae1/ae3), and panmelanoma. kappa and lambda dual stain was consistent with kappa predominance, and ki67 showed a proliferation rate of approximately 50%. the morphologic and ihc features support the diagnosis of plasmacytoma. tissue cultures were negative for fungus and acid-fast bacteria. a bone marrow aspirate and biopsy of the left posterior superior iliac spine revealed a normal percentage of plasma cells (3%) with no evidence of a clonal plasma cell population. positron emission tomography (pet) scan showed innumerable nodules of the right leg with the depth of involvement of the largest lesion ranged between 1.1 to 2.3 cm on the right lower leg without any signs of metastasis or bone involvement. serum and urine protein electrophoresis were both negative. although a nonspecific marker, beta 2 microglobulins were elevated, light chain ratio and serum protein electrophoresis were within normal limits. taken together, our patient did not meet the international myeloma working group (imwg) criteria for diagnosis of mm and had no evidence of underlying bone marrow involvement2. thus, a diagnosis of pcp was made based on clinical and histopathological features. due to his underlying comorbidities and questionable ability to recover from a definitive radiotherapy dose and possible complications including radiation dermatitis, he instead underwent palliative radiation with a dose of 2000cgy in 10 fractions over 2 weeks. the patient responded to the therapy with decrease in size of all the lesions. the patient died 6 months after diagnosis and palliative treatment of cardiac arrest unrelated to the diagnosis of pcp. plasma cell neoplasms can be classified into the following types: mm (bone marrow and other organ system involvement) and solitary plasmacytoma (sp) that can present either as emp in soft tissues or as solitary bone plasmacytoma (sbp)3,4. most plasmacytomas are seen in the setting of mm (94%)3,4 , especially in advanced myeloma with poor prognosis5. sp is a localized clonal plasma cell infiltration either in the bone or extramedullary sites without systemic disease. to be considered sbp or emp, bone marrow biopsy should demonstrate less than 10% plasma cells, and imwg criteria should not be met. otherwise, it would be classified as mm. discussion skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 699 figure 1: right lower leg with erythematous to violaceous nodules a) and eroded nodule with heme crusting b) on a background of stasis dermatitis and xerosis. figure 2: skin biopsy shows expansile nodular plasmacytoid cell infiltrate in the deep dermis underlying epidermis e) 1a) infiltrate is strongly positive for cd138 by immunohistochemistry confirming plasmacytoma p) 1b) (1a, hematoxylin and eosin 100x; 1b immunoperoxidase 40x) primary cutaneous plasmacytomas are even more rare type of emp confined to only skin without underlying systemic disease6. pathogenesis in some pcps has been associated with immunosuppression and viral infections7. clinically, cutaneous plasmacytomas manifests as indurated flesh colored, erythematous, or violaceous nodules or plaques and can be found anywhere on the body5,7. they can be solitary or multiple, with the reported prevalence of multiple lesions ranging from 38-44% 6,8. caers et al published recommendations for the diagnosis, treatment, and prognosis of sps3. diagnosis is made on the basis of a tissue biopsy with a diffuse dermal infiltrate of atypical and pleomorphic plasma cells, which are positive for cd138 and/or cd383. monoclonality can be confirmed with kappa or lambda light chain restriction by polymerase chain reaction (pcr), ihc, or in situ hybridization. all patients presenting with a new sp should be evaluated with a skeletal survey or computed tomography (ct). magnetic skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 700 resonance imaging (mri) and pet/ct3 are also required to rule out additional lesions as well as mm. although emps, including pcp, are usually indolent, 10% to 30% of emps progress to mm within 10 years3,4. presence of clonal cell population in bone marrow and the presence of additional lesions on pet/ct are negative prognostic factors and should be included in the initial assessment. patients with solitary lesions have a longer recurrence-free survival of 11 years compared to 1.4 years for patients with multiple lesions9. furthermore, patients with multiple skin lesions have higher mortality from disseminated disease. taken together, multiple lesions at the initial presentation are likely to be a predictor of poorer outcomes and subsequent disease progression6,9,10. for treatment, radiation therapy is considered standard for emp4. for local disease, as in pcp, surgery is also an option to resect large masses but should be followed by adjuvant radiotherapy3. for those patients presenting with multiple pcp lesions or persistent disease, additional benefit may be gained from systemic chemotherapy to prevent progression to mm9. serum protein electrophoresis and immunofixation as well as the same imaging methods should be closely followed to assess the treatment response. currently, additional clinical trials are underway to test the role of adjuvant chemotherapy including conventional chemotherapy, novel mm agents, immunomodulatory agents, and monoclonal antibodies3. the distinction of pcp as a unique entity is a matter of debate. there are some who would categorize them as primary cutaneous marginal zone lymphomas (pcmzl) of mucosa-associated lymphoid tissue with plasma cell differentiation5,8 as they show clinical and immunologic phenotype overlap. in fact, the whoeortc classify pcps with pcmzl11. as a distinguishing feature, the latter are generally cd20 positive and cd10 whereas the former express the opposite5,11. pcmzls are generally low-grade malignancies with low rates of disease progression and recurrence; the disease specific 5-year survival approaches 100%11. pcps in contrast have the potential to progress, metastasize, and cause significant mortality, especially when multiple nodules are present, with up to 50% of reported patients developing systemic involvement and a median overall survival of 10.4 years9,12. surgical excision and radiotherapy are standard treatment approach for both of these conditions9,11. plasma cell neoplasms encompass various clinical entities including mm, sbp, and emp, with pcp involving the skin and soft tissue. pcp is a very rare entity and shows considerable clinical and phenotypic overlap with pmzcl. the present case describes multiple nodules as opposed to a solitary neoplasm, which likely represents a spectrum of variation of one tumor. before sbp or emp is considered, systemic involvement must be ruled out, and close follow-up is recommended to detect potential progression to mm. conflict of interest disclosures: none funding: none corresponding author: suzanne alkul, md 1977 butler blvd houston, tx 77030 phone: 713-798-6131 email: alkul@bcm.edu references: 1. wiltshaw e. the natural history of extramedullary plasmacytoma and its relation conclusion skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 701 to solitary myeloma of bone and myelomatosis. med (united states). 1976;55(3):217-238. doi:10.1097/00005792197605000-00002 2. rajkumar sv, dimopoulos ma, palumbo a, et al. international myeloma working group updated criteria for the diagnosis of multiple myeloma. lancet oncol. 2014;15(12):e538e548. doi:10.1016/s1470-2045(14)70442-5 3. caers j, paiva b, zamagni e, et al. diagnosis, treatment, and response assessment in solitary plasmacytoma: updated recommendations from a european expert panel. j hematol oncol. 2018;11(1):10. doi:10.1186/s13045-017-0549-1 4. tsang rw, campbell ba, goda js, et al. radiation therapy for solitary plasmacytoma and multiple myeloma: guidelines from the international lymphoma radiation oncology group. int j radiat oncol biol phys. 2018;101(4):794-808. doi:10.1016/j.ijrobp.2018.05.009 5. rongioletti f, patterson jw, rebora a. the histological and pathogenetic spectrum of cutaneous disease in monoclonal gammopathies. j cutan pathol. 2008;35(8):705-721. doi:10.1111/j.16000560.2007.00884.x 6. muscardin a lm, pulsoni b a, cerroni c l. primary cutaneous plasmacytoma: report of a case with review of the literature. j am acad dermatol. 2000;43(5):962-965. doi:10.1067/mjd.2000.103997 7. walby ml, ahluwalia j, mehregan dr. primary cutaneous plasmacytoma in an hivpositive patient. int j dermatol. 2016;55(4):464-467. doi:10.1111/j.13654632.2012.05764.x 8. schmid u, eckert f, griesser h , et al. cutaneous follicular lymphoid hyperplasia with monotypic plasma cells. a clinicopathologic study of 18 patients. am j surg pathol. 1995;19(1):12-20. doi:10.1097/00000478199501000-00002 9. tsang ds, le lw, kukreti v, sun a. treatment and outcomes for primary cutaneous extramedullary plasmacytoma: a case series. curr oncol. 2016;23(6):e630e646. doi:10.3747/co.23.3288 10. miyamoto t, kobayashi t, hagari y, mihara m. the value of genotypic analysis in the assessment of cutaneous plasmacytomas. br j dermatol. 1997;137(3):418-421. doi:10.1046/j.1365-2133.1997.18611931.x 11. willemze r, jaffe es, burg g, et al. whoeortc classification for cutaneous lymphomas. blood. 2005;105(10):3768-3785. doi:10.1182/blood-2004-09-3502 12. kazakov d v., belousova ie, müller b, et al. primary cutaneous plasmacytoma: a clinicopathological study of two cases with a long-term follow-up and review of the literature. j cutan pathol. 2002;29(4):244248. doi:10.1034/j.1600-0560.2002.290408.x introduction objective methods results baseline characteristics ● a 10-fold greater reduction from baseline was seen for tralokinumab versus placebo in the full population (ratio=0.09; p<0.0001) at week 16 (figure 4) ● use of rescue therapy did not impact the results neutralizing interleukin-13 increases skin microbial diversity: results from a phase 3, randomized, double-blind, placebo-controlled trial of tralokinumab in adult patients with atopic dermatitis thomas bieber,1 lisa a beck,2 andrew pink,3 hidehisa saeki,4 lawrence eichenfield,5 thomas werfel,6 anders rosholm,7 mads røpke,7 amy paller8 1department of dermatology and allergy, university hospital, bonn, germany; 2department of dermatology, medicine and pathology, university of rochester medical center, rochester, ny, usa; 3st. john's institute of dermatology, guy’s and st. thomas’ hospitals, london, uk; 4department of dermatology, nippon medical school, tokyo, japan; 5departments of dermatology and pediatrics, university of california san diego school of medicine, san diego, ca, usa; 6department of dermatology and allergy, hannover medical school, hannover, germany; 7leo pharma a/s, ballerup, denmark; 8department of dermatology, feinberg school of medicine, northwestern university, chicago il, usa ● a healthy skin barrier supports the growth of commensal bacteria that protect the host from pathogenic bacteria and their virulence factors ● in atopic dermatitis (ad), recent studies have pointed to a lack of microbial diversity in lesional and non-lesional skin ● people with ad have high levels of staphylococcus aureus colonizing both lesional and non-lesional skin1 ● dysregulation of the skin microbiome in ad is believed to be influenced by epidermal barrier disruption and th2-driven inflammation, in which the il-13 cytokine plays a major role ● tralokinumab is a fully human, high-affinity monoclonal antibody that neutralizes the il-13 cytokine, and has been shown to improve signs and symptoms in adults with moderate-to-severe ad2,3 ● to examine the impact of tralokinumab treatment on microbial diversity in lesional skin of adults with moderate-to-severe ad from the phase 3 ecztra 1 trial (nct03131648) study design (figure 1) ● bacteria were collected from areas (5 x 10 cm) of lesional skin ● s. aureus and overall bacterial abundance was assessed in subjects in ecztra 1 (n=780) at baseline and week 16 using qpcr of the fema gene and the 16s rrna using the ba04230906 and ba04230899 assays from thermo fischer, respectively ● microbiome profiling was done in 84 subjects (59 on tralokinumab and 25 on placebo) at selected sites from ecztra 1 at baseline, week 8, and week 16 ● relative microbial abundance and shannon diversity were assessed based on dna sequencing of 16s ribosomal rna v3-v4 regions ● a total of 30,276 amplicon sequence variants (asvs) representing known taxa were identified from 205 samples. after filtering for asvs found in more than one sample, a total of 9,130 asvs were used for analysis representing 21 phyla, 468 genera and 791 species ● serum biomarkers were also measured (il-13 and il-22 in singulex erenna array; ccl17 by elisa) conclusions figure 2. s. aureus abundance correlates with select biomarkers at baseline 10 -1 10 0 10 1 10 2 10 0 10 1 10 2 10 3 10 4 10 5 10 6 il-13 il-13 (pg/ml) s .a u re u s (g e n e c o p ie s/ c m 2 ) p<0.0001 r=0.3545 10 0 10 1 10 2 10 3 10 4 10 0 10 1 10 2 10 3 10 4 10 5 10 6 il-22 il-22 (pg/ml) s .a u re u s (g e n e c o p ie s/ c m 2 ) p<0.0001 r=0.4340 10 2 10 3 10 4 10 5 10 0 10 1 10 2 10 3 10 4 10 5 10 6 ccl17/tarc ccl17 (pg/ml) s .a u re u s (g e n e c o p ie s/ c m 2 ) p<0.0001 r=0.3521 figure 3. correlation of change in s. aureus abundance with change in easi score -100 -50 0 50 100 10 -6 10 -5 10 -4 10 -3 10 -2 10 -1 10 0 10 1 10 2 10 3 tralokinumab change in easi from baseline to week 16 (%) c h a n g e in s .a u re u s a b u n d a n c e (w e e k 16 /b a se lin e ) p<0.0001 r=0.284 -100 -50 0 50 100 10 -5 10 -4 10 -3 10 -2 10 -1 10 0 10 1 10 2 10 3 10 4 placebo change in easi from baseline to week 16 (%) c h a n g e in s .a u re u s a b u n d a n c e (w e e k 16 /b a se lin e ) p<0.0001 r=0.430 figure 4. treatment with tralokinumab led to a greater reduction in s. aureus abundance in lesional skin relative to placebo at week 16 placebo tralokinumab baseline week 16 baseline week 16 10 0 10 1 10 2 10 3 10 4 10 5 10 6 s .a u re u s (g e n e c o p ie s /c m 2 ) p<0.0001 p<0.0001 p=0.182 figure 7. relative abundance of the most dominant staphylococcus species over time 0.0 0.1 0.2 0.3 0.4 0.5 0.6 staphylococcus species relative to all bacteria a ve ra g e o f sp e c ie s p e r sa m p le g ro u p 0.0 0.2 0.4 0.6 0.8 1.0 staphylococcus species relative to the genus a ve ra g e o f sp e c ie s p e r sa m p le g ro u p s. aureus s. caprae (cons) s. capitis (cons) s. epidermidis (cons) s. haemolyticus (cons) s. warneri (cons) s. lugdunensis (cons) s. argenteus s. schleiferi (cons) s. saprophyticus (cons) s. pettenkoferi (cons) s. cohnii (cons) other species placebo tralokinumab placebo tralokinumab baseline week 16 week 8 baseline week 16 week 8 baseline week 16 week 8 baseline week 16 week 8 figure 5. treatment with tralokinumab led to increased shannon diversity 0 1 2 3 4 5 s h a n n o n d iv e rs it y week 8 baseline * p<0.05 ** p<0.01 *** p<0.001 placebo tralokinumab figure 6. relative abundance of the most dominant phyla and genera over time 0.0 0.2 0.4 0.6 0.8 1.0 a ve ra g e p ro p o rt io n o f m a jo r p h yl a a n d g e n u s staphylococcus streptococcus lactobacillus brochothrix other firmicutes corynebacterium micrococcus dermacoccus kocuria other actinobacteriota moraxella acinetobacter paracoccus haemophilus photobacterium brucella other proteobacteria chryseobacterium prevotella porphyromonas bacteroides other bacteroidota other phyla bacteriodota proteobacteria actinobacterota firmicutes placebo tralokinumab baseline week 16 week 8 baseline week 16 week 8 figure 1. ecztra 1 trial design and microbiome sample collection. ecztra 1: phase 3, randomized, double-blind, placebo-controlled trial tralokinumab 300 mg q2w placebo q2w tralokinumab 300 mg q2w tralokinumab 300 mg q4w alternating with placebo placebo q2w placebo q2w tralokinumab 300 mg q2w optional tcs and optional home use initial treatmentscreening maintenance treatment patients with clinical response iga-0/1 or easi-75 ytefas follow-up open-label treatment ecztra 1 (n=603) ecztra 1 (n=199) 3:1 randomization patients not achieving iga=0/1 or easi-75 at 16 weeks patients transferred from temeraairetirccificepsfitnemtaertecnanetniam up to 6 weeks washout of ad medication (2 weeks for tcs) laitiniretfaw2qgm003 loading dose (600 mg) 2:2:1 randomization 16 weeks0–6 weeks 52 weeks 66 weeks4 8 28 weeks ad, atopic dermatitis; easi, eczema area and severity index; iga, investigator’s global assessment; q2w, every 2 weeks; q4w, every 4 weeks; tcs, topical corticosteroid. characteristic all randomized (n=802) skin swab (microbiome) subgroup (n=84) tralokinumab q2w (n=59) placebo (n=25) age mean (sd) 38.8 (14.1) 39.9 (13.8) 36.8 (13.1) sex, n (%) male 474 (59.1) 37 (62.7) 16 (64.0) female 328 (40.9) 22 (37.3) 9 (36.0) race, n (%) white 564 (70.3) 48 (81.4) 22 (88.0) black 59 (7.4) 2 (3.4) 1 (4.0) asian 160 (20.0) 8 (13.6) 2 (8.0%) iga, n (%) moderate disease 391 (48.8) 23 (39.0) 14 (56.0) severe disease 407 (50.7) 36 (61.0) 11 (44.0) easi mean (sd) 32.4 (13.8) a 35.6 (14.7) 32.8 (13.1) scorad mean (sd) 70.6 (12.9) a 74.2 (13.1) 72.1 (10.5) dlqi mean (sd) 16.9 (7.0) b 17.7 (6.6) d 18.3 (6.6) worst daily pruritus nrs (weekly average) mean (sd) 7.7 (1.4) c 8.1 (1.4) 8.1 (1.2) table 1. baseline demographics and clinical characteristics for randomized subjects in parent study (ecztra 1) and in the skin swab subgroup. s. aureus abundance ● at baseline, s. aureus abundance was moderately correlated with il-13, il-22, and ccl17/tarc serum levels based on a non-parametric spearman correlation (figure 2) ● patients with the greatest reduction in s. aureus abundance from baseline to week 16 also had the greatest improvement in easi score (figure 3) microbiome diversity ● the tralokinumab group showed a significant increase in microbial diversity over time and relative to the placebo group at week 8 and week 16 (figure 5) ● the results are presented as shannon diversity index, which is a quantitative measure of how many bacterial species are present on the skin and also accounts for the phylogenetic relations between the different species ● relative abundance of major phyla and genera remained stable for patients receiving placebo, while the relative abundance of staphylococcus was reduced 47.5% from baseline for the tralokinumab group (figure 6) ● at the species level, the overall decrease in the relative abundance of staphylococcus was primarily due to decreased relative abundance of s. aureus, from comprising almost 32% of all bacteria at baseline to less than 8% of all bacteria at week 16 (figure 7) ● relative abundance also decreased for s. argenteus, a pathogenic hemolysin-producing species associated with s. aureus, from 5% of staphylococcus at baseline to 2% at week 16 ● in contrast, the relative abundance of commensal coagulase-negative staphylococci (cons), such as s. epidermidis and s. capitis, were moderately increased microbiome dysbiosis skin barrier dysfunction neutralizing il-13 cytokine with tralokinumab modulates type 2 immunity4 tralokinumab treatment shifts both inflammatory mediators and skin barrier markers towards a nonlesional profile5 tralokinumab treatment increased skin microbial diversity il-13↑↑ immune dysregulation references 1. ogonowska p et al. front. microbiol. 2021; 11:567090; 2. wollenberg a et al. br j dermatol. 2020 sep 30. doi: 10.1111/bjd.19574. online ahead of print; 3. silverberg et al. br j dermatol. 2020 sep 30. doi: 10.1111/bjd.1957 3. online ahead of print; 4. guttman-yassky e, et al. poster presentation at aad vmx 2021; 5. guttman-yassky e, et al. late-breaking presentation at aad vmx 2021. disclosures thomas bieber is an advisor/speaker/researcher for abbvie, allmiral, anaptysbio, arena, asana biosciences, astellas, bayer, bioversys, boehringer ingelheim, celgene, daiichi sankyo, dermavant/roivant, dermtreat, domain therapeutics, ds biopharma, rapt therapeutics (flx bio), galapagos/morphosys, galderma, glenmark, glaxosmithkline, incyte, kymab, leo pharma, lilly, l´oréal, menlo therapeutics, novartis, pfizer, pierre fabre, sanofi/regeneron, and ucb. lisa a beck is an investigator and consultant for abbvie, astra-zeneca, leo pharma, pfizer, regeneron and sanofi, and reports consulting fees and/or honoraria from benevolent aibio, dermtech, incyte, janssen, lilly, novartis, principia biopharma, rapt therapeutics, regeneron, sanofi/genzyme and sanofiaventis. she is an investigator for kiniksa. andrew pink reports personal fees and nonfinancial support from leo pharma, novartis, and ucb; and personal fees from abbvie, almirall, janssen, la roche posay lilly, and sanofi. hidehisa saeki is an advisor to leo pharma. lawrence eichenfield has served as an advisor/speaker/researcher for abbvie; almirall, arcutis, arena, dermira, forte, galderma glenmark/ichnos,,incyte, leo pharma, lilly, novartis, pfizer, ortho dermatology regeneron,and sanofi genzyme. thomas werfel has received lecture or consultancy fees from abbvie, almirall, astellas, galderma, janssen/johnson & johnson, leo pharma, lilly, novartis, pfizer, and regeneron/sanofi. anders rosholm was an employee of leo pharma. mads røpke is an employee of leo pharma. amy paller has served as an investigator for abbvie, anaptysbio, incyte, janssen, leo pharma, lilly, lēnus, novartis, regeneron, and ucb and received honorarium for consultancy from abbvie, abeona, almirall, asana biosciences, boehringer ingelheim, bridgebio, dermavant, dermira, exicure, forté pharma, galderma, incyte, inmed, janssen, leo pharma, lilly, lifemax, novartis, pfizer, rapt therapeutics, regeneron, sanofi genzyme, sol-gel, and ucb acknowledgements the ecztra 1 clinical trial was sponsored by leo pharma originally presented at american academy of dermatology (aad) vmx, april 23-25, 2021. ● tralokinumab treatment was associated with decreased abundance of s. aureus and increased microbial diversity in lesional skin the results support that neutralization of the il-13 cytokine contributes to improving the hallmarks of ad by shifting the microbial diversity on ad lesional skin towards commensal flora an=798; bn=785; cn=793; dn=57 skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 170 short communications desmoplastic malignant melanoma clinically presenting as a “cyst” haley d. heibel, md1, robin burger, md2, and clay j. cockerell, md, mba3,4 1 department of dermatology, northwestern university feinberg school of medicine, chicago, il 2 advanced dermatology and cosmetic surgery, delray beach, fl 3 cockerell dermatopathology, dallas, tx 4 departments of dermatology and pathology, ut southwestern medical center, dallas, tx we recently reviewed the histopathology of an excision of a lesion that had been clinically diagnosed and managed as a cyst. the lesion was present on the back of a 58year-old female (figure 1) and had been injected with intralesional steroids for over one year with minimal improvement, which led to a biopsy. figure 1. desmoplastic melanoma. this lesion presented clinically as a “cyst.” histopathologic analysis of the excision revealed an atypical proliferation of pleomorphic spindle cells in a desmoplastic stroma with lymphoid aggregates in the dermis extending near to the subcutaneous fat (figure 2). immunohistochemical stains were positive for sox-10 and negative for cd34 and cd68 confirming the diagnosis of desmoplastic malignant melanoma (dmm). figure 2. histology of desmoplastic melanoma (h&e, 40x) demonstrating an atypical proliferation of pleomorphic spindle cells in a desmoplastic stroma with lymphoid aggregates in the dermis extending to near the subcutaneous fat. dmm often eludes clinical diagnosis as it usually does not have characteristic features of melanoma. many lesions are not pigmented and may present as an indurated plaque or nodule often on the head and neck region.1-3 they may clinically resemble skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 171 a scar, dermatofibroma, neurofibroma, fibromatosis, basal cell carcinoma, or squamous cell carcinoma, which may lead to misdiagnosis and a delay in appropriate treatment.2,4 comprising less than 2-4% of primary cutaneous melanomas, the rarity and lack of characteristic morphology may impede the correct clinical diagnosis of dmm.2,4 over the last number of years, we have histologically diagnosed 7 cases of dmm that were submitted by well-trained and experienced dermatologists with a clinical impression of “cyst.” while a number of different entities, including serious malignancies such as metastatic neoplasms, may be thought to be cysts clinically, dmm is not a lesion that is characteristically thought to present as a cyst. thus, this is a cautionary note to alert dermatologists that dmm should be considered in the clinical differential diagnosis of a cyst in some cases. when a lesion that is thought to be a cyst has an unusual morphology or does not respond to therapy in a reasonable time, a biopsy should be performed in a fashion that will allow for an accurate diagnosis to be rendered. an incisional or excisional biopsy may be preferred, given that dmm may be difficult to diagnose histologically as well. delay in diagnosis can lead to adverse patient outcomes and medicolegal liability. the knowledge that dmm may present clinically as a “cyst” can lessen the likelihood of such delay and avoid these consequences.2 conflict of interest disclosures: none funding: none corresponding author: haley d. heibel, md 875 north michigan avenue suite 1525 chicago, il 60611 phone: (312) 227-6817 fax: (312) 227-9402 email: haley.heibel@northwestern.edu references: 1. barnhill rl, gupta k. unusual variants of malignant melanoma. clin dermatol. 2009;27(6):564-587. 2. cabrera r, recule f. unusual clinical presentations of malignant melanoma: a review of clinical and histologic features with special emphasis on dermatoscopic findings. am j clin dermatol. 2018;19 (suppl 1):15-23. 3. rongioletti f, smoller br. unusual histological variants of cutaneous malignant melanoma with some clinical and possible prognostic correlations. j cutan pathol. 2005;32(9):589-603. 4. chen ll, jaimes n, barker ca, busam kj, marghoob aa. desmoplastic melanoma: a review. j am acad dermatol. 2013;68(5):825-833. patient assessment of foam attributes from the tazarotene foam 0.1% phase iii trials and potential impact on patient compliance_schreiber et al 2018 final pa�ent assessment of foam a�ributes from the tazarotene foam, 0.1%, phase iii trials and poten�al impact on pa�ent compliance rhonda schreiber bscn, mssl; caitlin lewis, phd; kaytiana crane bs tazarotene is the only re�noid approved for use in a foam vehicle, and as such, is uniquely situated to offer the benefits of such a formula�on to acne sufferers. w hilst its safety and efficacy are well established, the data presented here are the first to examine pa�ent preference for the foam vehicle compared to other formula�ons and intent to comply with physician instruc�ons. it has been previously well established that topical vehicle impacts not only safety, efficacy, and tolerability, but also pa�ent preference and therefore adherence to treatment protocols.3,4 this data clearly shows that the foam formula�on rated strongly in a range of proper�es which other studies have found to be important to pa�ents when choosing a topical vehicle.2 in addi�on, the foam was rated the most favorable formula�on by 51% of study par�cipants, with the next highest being cream at 17%. perhaps most significantly, when par�cipants were asked if they would use the foam product once a day for 12 weeks, 85% said they would comply 75-100% of the �me. it is noted that no direct data has been collected on compliance rates amongst users of tazarotene foam, 0.1%. however, the data presented here strongly suggest that the favorable a�ributes the foam were preferred by par�cipants and, as has been noted in other studies, posi�ve pa�ent preference can lead to increased compliance and therefore be�er treatment outcomes for acne sufferers. 1. demircay z, seckin d, senol a, demir f. eur j dermatol. 2008 mar-apr;18(2):181-4. 2. dréno b, thiboutot d, gollnick h, finlay ay, layton a, leyden jj, leutenegger e, perez m; global alliance to improve outcomes in acne. int j dermatol. 2010 apr;49(4):448-56. 3. baldwin, he dermatol ther. 2006 jul-aug;19(4): 224-236. 4. kircik lh. j drugs dermatol. 2011 jun;10(6):s17-23. 5. eastman wj, malahias s, delconte j, dibenede� d. cu�s. 2014 jul;94(1):46-53. 6. tan x, feldman, sr, et al. expert opin drug deliv. 2012 oct;9(10):1263-71. 7. smith ja, narahari s, hill d, feldman sr. expert opin drug saf. 2016 jan;15(1):99-103 8. feldman sr, werner cp, alió saenz ab. j drugs dermatol. 2013 apr;12(4):438-46. 9. epstein el, stein gold l. clin cosmet inves�g dermatol. 2013 may 14;6:123-5. 10. data on file; mayne pharma. acne vulgaris is a common chronic disease which can affect a pa�ent’s physical appearance and psychosocial func�on and o�en requires long term use of topical medica�ons. 1,3 while topical delivery of drugs in the treatment of dermatological condi�ons is an obvious front-line strategy, pa�ent compliance is a known recurring barrier to treatment success.2,3 lack of adherence to treatment strategy has been linked with both pa�ent dissa�sfac�on and poor treatment outcomes.2 adherence to treatment is governed by a range of factors including financial and clinical considera�ons. recent research also shows that pa�ent vehicle preference is an important, but o�en overlooked, factor in maintaining compliance.3-6 a worldwide study found that poor adherence occurs in 40% of pa�ents receiving topical treatment for acne.2 topical treatments for acne include formula�ons such as creams, lo�ons, ointments, gels, solu�ons and foams. vehicle choice has an impact not only on drug delivery and potency, but also cosme�c and pa�ent percep�on a�ributes.4 studies show that common concerns affec�ng pa�ent adherence to topical drug regimens in chronic skin condi�ons are the ability to be used all the �me, speed of absorp�on/disappearance, spreadability, ease of applica�on, messiness, ability to moisturize, and lack of greasiness, s�ckiness, and scent. 3,5 a�er drug efficacy, pa�ent preference should be a primary considera�on in choosing topical vehicles.3 tazarotene foam, 0.1% is the only re�noid in a foam vehicle, and it is well established as a safe, effec�ve, and well tolerated topical treatment for acne vulgaris.7-9 the data presented here highlight the results of pa�ent preference ques�onnaires, administered at the end of the tazarotene foam phase iii trials, related to evalua�on of the foam vehicle as well as other formula�ons previously used by study subjects for acne treatment.10 background • evaluate pa�ent preference for topical vehicle a�ributes. • examine the link between pa�ent preferences and adherence to treatment strategy. aims • two mul�center, randomized, double blind, vehicle controlled, parallel group phase iii studies were carried out, with 1485 pa�ents randomized in a 1:1 ra�o into two treatment groups either tazarotene foam, 0.1% (744) or vehicle foam (741). • par�cipants were aged 12-45 years with moderate to severe acne vulgaris. • study subjects were required to apply foam to the face once daily for 12 weeks and were permi�ed to apply to the trunk as well. • efficacy, safety, and tolerability assessments were carried out at baseline and at weeks 2, 4, 8, and 12. • at the week 12 (final) visit a pa�ent ques�onnaire was administered which incorporated ques�ons about formula�on a�ributes, preference for treatment vehicle, and intent to adhere to treatment. • the ques�onnaire results presented here have been integrated across the two studies and contain data for both tazarotene foam, 0.1% and vehicle-only cohorts. conclusions methods references results at the conclusion of the phase iii studies, par�cipants were given a ques�onnaire to complete regarding their personal preferences and experiences with the foam vehicle compared to other formula�ons they had used. approximately 94% of study subjects par�cipated in the ques�onnaire. they were unaware as to whether they were ra�ng vehicle or tazarotene foam. the most per�nent aspects are presented here. integrated intent-to-treat analysis set n=1485, n(%) 100% 75-99% 50-74% 25-49% �24% does not apply not answered foam 763 (51) 495 (33) 61 (4) 20 (1) 23 (2) 30 (2) 93 (6) gel 365 (25) 336 (23) 131 (9) 53 (4) 26 (2) 479 (32) 95 (6) cream 481 (32) 443 (30) 138 (9) 48 (3) 30 (2) 250 (17) 95 (6) lo�on 422 (28) 355 (24) 123 (8) 61 (4) 27 (2) 401 (27) 96 (6) solu�on 338 (23) 315 (21) 132 (9) 57 (4) 36 (2) 512 (34) 95 (6) integrated intent-to-treat analysis set n=1485, n(%) liked best 2nd best 3rd best 4th best liked least does not apply not answered foam 754 (51) 263 (18) 140 (9) 83 (6) 103 (7) 44 (3) 98 (7) cream 246 (17) 372 (25) 260 (18) 152 (10) 62 (4) 292 (20) 101 (7) gel 136 (9) 201 (14) 170 (11) 135 (9) 150 (10) 594 (40) 99 (7) lo�on 120 (8) 237 (16) 248 (17) 186 (13) 108 (7) 485 (33) 101 (7) solu�on 75 (5) 155 (10) 165 (11) 189 (13) 176 (12) 622 (42) 103 (7) 0% 10% 20% 30% 40% 50% 60% liked best 2nd best 3rd best 4th best liked least foam gel cream lo�on solu�on study popula�on gender n (%) age n(%) male 729 (49) 12-17 years 860 (58) female 756 (51) 18-25 years 428 (29) 26-35 years 143 (10) 36-45 years 54 (4) integrated intent-to-treat analysis set n=1485, n(%) excellent good fair poor very poor not answered easy to apply 856 (58) 381 (26) 127 (9) 20 (1) 8 (1) 93 (6) spreadability 764 (51) 440 (30) 152 (10) 28 (2) 8 (1) 93 (6) absorbs quickly 638 (43) 438 (29) 229 (15) 67 (5) 17 (1) 96 (6) lack of residue 392 (26) 499 (34) 330 (22) 113 (8) 58 (4) 93 (6) does not feel greasy 505 (34) 411 (28) 291 (20) 133 (9) 51 (3) 94 (6) fragrance-free 515 (35) 384 (26) 312 (21) 128 (9) 53 (4) 93 (6) lack of s�ckiness 603 (41) 432 (29) 262 (18) 75 (5) 19 (1) 94 (6) moisturizing 126 (8) 391 (26) 479 (32) 250 (17) 145 (10) 94 (6) 85% 62% 47% 52% 44% foam cream gel lo�on solu�on predicted compliance rate >75% for 12 weeks rate the foam on each of the following quali�es: moisturizing, lack of residue, does not feel greasy, absorbs quickly, easy to apply, fragrance-free, spreadability, lack of s�ckiness as can be seen below, the foam vehicle rated very strongly, largely as good or excellent, on all a�ributes. the excep�on being moisturizing, which is not surprising given that a number of subjects were ra�ng the ac�ve re�noid foam. for all skin medica�ons you have used in the past for acne, rate the following product types in the order you preferred them. the data show that the foam was rated by far the highest as first preference for treatment vehicle, with 51% of par�cipants ra�ng foam best. this is between 3 to 10 �mes greater than the number of those ra�ng other formula�ons best, with the next highest being cream at only 17% of subjects ra�ng it best. if you were asked by your doctor to put medica�on on your skin once daily for 12 weeks, how likely would you be to follow these instruc�ons based on the product type? the foam rated most strongly of all formula�ons, with 85% of par�cipants sta�ng that they would comply between 75-100% of the �me over a 12 week treatment course. 1. ms. schreiber and ms. crane are employees of mayne pharma. 2. dr. lewis is the director of clewy communica�ons. 3. this analysis and presenta�on was sponsored by mayne pharma and prepared by clewy communica�ons. 4. author contact informa�on: rhonda.schreiber@maynepharma.com disclosures 0 10 20 30 40 50 60 70 80 90 100 pe rc en t o f pa ti en ts excellent good fair poor very poor not answered skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 127 rising derm stars® photodynamic therapy with δ-aminolevulinic acid and blue light for the treatment of actinic cheilitis dagrosa at, md1, paul j, chen y, gangar p, ressler d, chapman ms 1department of dermatology, dartmouth hitchcock medical center, lebanon, nh background/objectives: actinic cheilitis is a common precancerous malformation of the lower lip caused by ultraviolet radiation. photodynamic therapy (pdt) is a potential treatment option for actinic cheilitis. however, controlled clinical trials assessing the efficacy of pdt for actinic cheilitis are lacking. pdt is based on the combined use of photosensitizers and photoradiation. topically applied δ-aminolevulinic acid (ala) is theorized to be taken up by premalignant cells. upon irradiation with a light source, photoactivated porphyrins produce singlet oxygen and other potent oxidizers, resulting in cell death.1,2 we hypothesized that the use of pdt with blue light and topical ala treatment is a safe and effective treatment for actinic cheilitis. methods: we conducted a single center, investigator-initiated, nonrandomized, openlabel, proof of concept study of topical ala and pdt with blue light for the treatment of actinic cheilitis. we enrolled 24 subjects with a diagnosis of actinic cheilitis; 20 of these subjects met inclusion and exclusion criteria for participation in the study. one subject withdrew from the study prior to treatment. the study consisted of a screening visit, one to three scheduled treatments with ala followed by pdt, and two follow-up visits. the primary outcome was assessed by the investigator at each visit as clinical improvement of actinic cheilitis from baseline. improvement was estimated as no (0%), mild (25%), moderate (50%), marked (75%), or excellent improvement (100%). posttreatment assessments based upon visual observation of swelling, vesiculation/pustulation, erosion/ulceration, erythema, flaking/scaling, and crusting were also completed. subjects completed the dermatological life quality index (dlqi) questionnaire and a subject global assessment of improvement at each visit. pain was also assessed at each treatment visit. results: of the 19 subjects that completed the study, 84.2% achieved clinical improvement of 75% or better based on investigator assessment (primary outcome). five subjects (26.3%) achieved 100% improvement by the end of the study. based on the subjects’ assessment of improvement, 68.4% achieved improvement of 75% or better by the end of the study. treatments were well tolerated with minimal discomfort. many subjects had transient adverse effects of treatment including swelling, erythema, and flaking/scaling; few subjects had more serious adverse effects such as vesiculation/pustulation or crusting. no subjects experienced erosion/ulceration. skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 128 conclusion: overall our study supports the use of topical ala and pdt as a therapeutic option for the treatment of actinic cheilitis. references: 1. choudhary s, nouri k, elsaie ml. photodynamic therapy in dermatology: a review. lasers med sci. 2009;24(6):971-980. 2. 2. akimoto m, maeda k, omi t, nishimura t, miyakawa m. photodynamic therapy in the dermatological field and enhanced cutaneous absorption of photosensitizer. progress in electromagnetics research symposium, cambridge, ma. sess 2a7. 2010:314. skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 590 in-depth review pathophysiology, risk factors, and prevention of wound dehiscence following dermatologic procedures andrew m. armenta, md1, frank t. winsett, md1, richard f. wagner jr. md1 1department of dermatology, the university of texas medical branch, galveston, tx skin cancer is the most common malignancy in the united states and has been increasing in incidence, affecting approximately one in five americans.1,2 as the number of skin cancers have increased, so have the number of dermatologic procedures including biopsies, excisions and mohs micrographic surgery.2 behind surgical site infection, wound dehiscence is the second most common postoperative complication of dermatologic procedures and often occurs within the first postoperative week.3-6 there are many preoperative, intraoperative, and postoperative risk factors that must be considered to decrease the risk for this common complication. physiology of wound healing wound healing is separated into four overlapping phases: hemostasis, inflammation, proliferation, and maturation.7 if any of these stages are impaired, wound healing may be compromised. hemostasis begins immediately following a break in the skin with bleeding and release of factors that activate the extrinsic and intrinsic coagulation pathways and promote platelet aggregation.7 the platelet plug is subsequently reinforced with a fibrin network upon which inflammatory cells migrate. during the inflammatory phase, neutrophils and macrophages migrate into the wound and are involved in clearance of pathogens, removal of cellular debris, and the release of various growth factors, setting the stage for the proliferative phase.8 within 48 hours the proliferative phase begins with the formation of granulation tissue. during the proliferative phase fibroblasts replace the fibrin network abstract skin cancer is the most common malignancy in the united states and has been increasing in incidence, affecting approximately one in five americans. as the number of skin cancers have increased, so have the number of dermatologic procedures including biopsies and excisions. behind surgical site infection, wound dehiscence is the second most common postoperative complication of dermatologic procedures. there are many preoperative, intraoperative, and postoperative risk factors for wound dehiscence. the current literature on the risk factors of dehiscence within the field of dermatology is scarce. to our knowledge, there have not been any comprehensive reviews on this topic. our research article aims to serve as a comprehensive and concise review with the goal of educating providers and increasing awareness of the risk factors associated with wound dehiscence. introduction review skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 591 with collagen, myofibroblasts mediate wound contraction, and angiogenesis with neovascularization occurs. concurrently, keratinocytes re-epithelialize the wound by migrating from the wound edges and remaining adnexal structures. the fourth and final stage is maturation or remodeling of the wound, which begins 2-3 weeks after wound development and can continue to 1 year. during remodeling, reorganization, degradation and resynthesis of the extracellular matrix occurs and the wound achieves its maximum tensile strength as type iii collagen is replaced by type i collagen.8 the driving force in wound dehiscence is tension. if the tension applied to the wound is greater than that of the tensile strength of epidermis, dermis, and the wound repair materials, dehiscence will occur. scar strength increases during the remodeling phase to a maximum tensile strength of approximately 80% of uninjured skin. depending on anatomic location and surgeon preference, sutures are typically removed between 7-14 days postoperatively. it is important to note, the tensile strength of a postoperative wound is typically less than 5% of normal skin at 1 week and less than 10% at 2 weeks.9 risk factors for wound dehiscence surgical training and experience experience, training, and technical ability all play a role in post-operative outcomes of dermatologic procedures. studies suggest that the experience of the surgeon is more significant than patient-related factors in acute wound failure and dehiscence.10,11 two studies have demonstrated that fellowship trained mohs surgeons have a lower rate of wound dehiscence (0.10% and 0.33%) when compared to non-fellowship trained mohs surgeons (0.93%).6,12,13 anatomical location certain areas of the body are intrinsically more tensile than others. extra care should be taken in areas of high tension including the scalp, back, proximal upper extremities and over joints.11,14 these locations have high tension due to movement, stretch and thick dermis. areas with increased mobility around the joints, legs, lips and eyelids are at increased risk of dehiscence.15 additionally, areas prone to trauma such as the distal arms and legs are higher risk for wound dehiscence. delayed or slow wound healing, as is often observed on the distal lower extremities, can also be a risk factor for wound dehiscence.3 poor perfusion can lead to insufficient oxygen and nutrient delivery needed for proper wound healing.3 the lower extremities are also at increased risk of venous stasis which can lead to increased tension on the surgical site from swelling. method of closure when performing excisions, the axis of the wound can greatly impact the cosmetic outcome and risk of dehiscence and depends on anatomic location. langer’s lines were first proposed by karl langer in 1831 as lines of cleavage oriented parallel to collage fibers in the dermis.16 later, cornelius kraissl proposed his own set of anatomic skin lines, kraissl’s lines, that run parallel to natural skin creases and perpendicular to underlying muscle fibers.17 while there is significant overlap between langer’s lines and kraissl’s lines, they differ in certain areas such as the face and abdomen and excisions following kraissl’s lines tend to be under less tension and skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 592 result in better cosmetic outcomes.17 more recently, a set of biodynamic excisional skin tension (best) lines have been proposed using a tensiometer to measure tension vectors and determine lines of least tension following circular excisions.16 elliptical excisions are preferred over circular excisions, generally in a 3:1 length to width ratio, as they further reduce tension and prevent the formation of standing cones. of note, vectors of tension may change with changes in position and movement and the axis of elliptical excisions should be decided in a neutral resting position. healing wounds have an increased demand for oxygen and nutrients compared to normal skin. when suturing a surgical defect excessive tension on sutures may lead to tearing of tissue or breaking of suture and result in wound dehiscence.3,18 additionally, tight suture may strangulate the edges of the wound leading to poor perfusion and necrosis. adequate undermining is often necessary to relieve tension and prevent dehiscence when approximating edges of a surgical wound.19 in areas of high tension, surgical techniques such as layered closure, mattress sutures, “pulley stitch,” “gliding stitch,” “winch stitch,”, or relaxing skin incisions have proven useful in securely approximating wounds.20-24 if additional support is needed, adhesive strips or other mechanical devices can be utilized.25 in some cases, the size and tension of the defect is too great to be closed by primary intention. in these cases, skin grafts and flaps may be used to reduce or redistribute tension on surgical wounds in order to prevent dehiscence.12,13,19 surgical material suture material plays an important role in dehiscence rates. one study comparing postoperative dehiscence rates of polyglactin 910 (vicryl®), polyglecaprone 25 (monocryl®), and polydioxanon (pds®) found the rates significantly varied at 10.8%, 12.3%, and 4.7%, respectively. the same study found inflammatory reactions were greatest with polyglactin 910 and least with polydioxanone.24 further, too small caliber sutures may break or tear through tissue leading to dehiscence.11 removing sutures too soon may also contribute to dehiscence. if prolonged support is needed, sutures may be removed in stages or adhesive strips may be used.25 similarly, the application of a pressure bandage immediately postoperatively may help prevent postoperative bleeding as well as hematoma or seroma formation which may lead to dehiscence.15 infection infection is a major risk factor for wound dehiscence. a study in mohs surgery patients found that infection led to a 25% chance of dehiscence.12 postoperative wound infection can delay wound healing by prolonging the inflammatory phase and delaying progression of the proliferative and maturation phases.3 surgical sites that are high risk for infection and impaired wound healing include the groin, armpits, hands, and lower extremities.26-28 skin biopsies performed on hospitalized patients are much higher risk for postoperative infection compared to outpatient dermatologic procedures.26 hematoma formation when postoperative bleeding occurs, a collection of blood may form resulting in a hematoma which can increase tension on the wound and lead to dehiscence. of note, flap and graft repairs are higher risk for hematoma formation when compared to skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 593 primary intention.12 skin grafts depend on imbibition early on for survival and hematoma development often leads to graft failure, necrosis, and dehiscence.12,13 areas of high vascularity such as the face and the scalp are also at increased risk for hematoma formation. patient adherence patient adherence to postoperative instruction plays an important role in preventing dehiscence. any significant tension placed on the wound early in the healing process may lead to dehiscence. therefore, patients should be given clear activity restrictions and instructed to avoid any activities such as heavy lifting, stretching or straining that may increase tension on the surgical site. for lower extremity wounds, patients with congestive heart failure or venous insufficiency are advised to elevate their legs when possible to decrease swelling. similarly, compressive dressings such as an unna boot may be used. patient demographics that that are associated with an increased risk of dehiscence include young age and male gender, likely due to poor adherence to activity restrictions.11 further, propensity for surgical site trauma and poor wound hygiene are also likely to play a role in dehiscence.29 genetic predisposition non-modifiable risk factors for dehiscence include genetic diseases, advanced age, and skin site reactions. genetic disorders with impaired collagen production like ehlers-danlos or dystrophic epidermolysis bullosa pose particular challenges during wound repair, as collagen synthesis is required for proper wound healing.7,30 patients who have bleeding disorders like hemophilia may also be at increased risks of dehiscence due to postoperative bleeding and hematoma formation.17 although younger age was found to be a risk factor for wound dehiscence, skin atrophy in advanced age can also contribute.26 with increasing age, collagen production decreases and skin becomes more fragile. gender may play a role in wound dehiscence behaviorally, but not biologically. falland-cheung et al found there were no significant differences when comparing the tensile strength of the scalp in males to females.14 allergic reactions to bandages, adhesives, and topical antibiotics may contribute to dehiscence.15 atherosclerosis, diabetes mellitus, and hypertension atherosclerosis is the narrowing of an arterial lumen due to abnormalities in the vessel wall.31 this narrowing limits the delivery of oxygen rich blood and nutrients to peripheral tissue and skin required for wound healing. impaired blood flow and nutrient delivery result in delayed wound healing and increased risk of dehiscence. the most common causes of atherosclerosis are diabetes, hypertension, smoking, and dyslipidemia.31 in addition to atherosclerosis, hyperglycemia in diabetics also interferes with nutrient absorption and endothelial function.32 similarly, hypertension causes additional oxidative stress, perivascular inflammation and fibrosis that impair wound healing.33 smoking it is well established that smoking is detrimental to vascular health and affects multiple phases of wound healing. in addition to contributing to atherosclerosis, skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 594 during the inflammatory phase smoking can alter cytokines and chemo-attractants and suppress the immune response, leading to an increased risk of infection.34 smoking also induces increased amounts of oxidative stress, vascular inflammation, promotes vasoconstriction, and promotes the release of fibrinogen leading to a hypercoagulable state.35 furthermore, carbon monoxide from smoking binds to hemoglobin, displacing oxygen impeding its delivery to healing wounds.35 smoking also decreases collagen synthesis and reduces protease inhibition. this blunts tissue formation and accelerates tissue destruction.35 overall, the tensile strength of postoperative wounds is weakened by impairing both proliferation and maturation. smokers who are undergoing dermatologic procedures should be counseled and encouraged to quit smoking prior to, and following surgery.36 smoking cessation prior to surgery was reported to decrease wound infection rates, but did not impact dehiscence.34 further, flaps and grafts should be avoided in these patients when possible due to higher failure rates. obesity obesity affects one third of adults in the united states and impairs multiple phases of wound healing leading to an increased risk of dehiscence.36 an obese body habitus often leads to decreased chest expansion causing hypoxia and decreased oxygen supply.37 the resultant hypoxia diminishes fibroblast collagen formation and cellular repair mechanisms.37 vasculogenic progenitor cells which normally contribute to wound angiogenesis also have impaired migration and proliferation in obese patients.38 dysfunctional vasculogenic progenitor cells and avascularity from surrounding adipose tissue decrease oxygen delivery to the wound.38 neutrophil and macrophage function are also impaired in obese patients causing a blunted immune response with increased risk of infection and dehiscence.37 malnutrition adequate caloric intake is required to support the inflammatory response, cellular activity, angiogenesis, and collagen synthesis required for wound healing.39,40 carbohydrates are needed for fibroblast production and migration, leukocyte activity and the secretion of hormones and growth factors.39 additionally, proteins like thrombospondin and albumin are essential for normal wound healing.40 without a sufficient amount of these macronutrients, wounds are at an increased risk of delayed healing and dehiscence. several micronutrients are also integral in would healing. for example, vitamin k is an important factor in the coagulation cascade and hemostasis. similarly, iron, zinc, and vitamins a, b, c, and d are essential to the inflammatory process and synthesis of collagen.32 in particular vitamin c (ascorbic acid) is a necessary cofactor in cellular apoptosis, clearance of neutrophils in the inflammatory phase, and collagen synthesis.41 impaired collagen production disrupts the proliferative and maturation phases of wound healing and scar formation. medications some medications have been demonstrated to increase the risk for wound dehiscence. for example, systemic retinoids such as isotretinoin, have been shown to impair collagen and non-collagen protein synthesis in fibroblasts, leading to dehiscence.42 further, dehiscence in mature scars (25 to skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 595 130 days old) have also been described following the initiation of isotretinoin.43 immunosuppressive medications are also problematic. steroids may impair interleukin signaling, cytoskeletal remodeling, and keratinocyte proliferation during the proliferative phases of wound healing.44 a retrospective assessment found immunosuppressed patients who underwent mohs surgery at an increased risk of dehiscence when compared to immunocompetent patients.4 similarly, mtor inhibitors (sirolimus, everolimus) and hedgehog pathway inhibitors (vismodegib, sonidegib) have been shown to increase the incidence of dehiscence.45,46 nsaids can also slow wound healing, acting mostly in the proliferative phase, thus increasing the risk of dehiscence.47 nsaids inhibit keratinocyte proliferation and angiogenesis through disruption of prostaglandin pge2 and pgd2 synthesis and vascular endothelial growth factor (vegf) expression, respectively.47,48 nsaids are often used to treat acute postsurgical pain so the benefit of analgesia must be weighed against the risk of dehiscence. multiple studies have shown that discontinuation of antiplatelet and anticoagulants may not be necessary prior to cutaneous surgery. significant differences in complications including postoperative bleeding and wound dehiscence have not been demonstrated.12,49,50 wound dehiscence is among the most common complications following dermatologic procedures. it can lead to increased healthcare costs, infection, bleeding, need for additional procedures, poor cosmetic outcomes and may affect patient satisfaction. there are many modifiable and non-modifiable risk factors for dehiscence (table 1) that must be identified in order to prevent this common complication. conclusion skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 596 table 1. risk factor mechanism phase(s) of wound healing affected surgical experience personal experience, skill, and knowledge of various surgical techniques anatomical location areas with tension areas with ¯ blood flow areas with blood flow areas with risk of swelling areas with close proximity to the ground/structures tension > skin + suture tensile strength ¯ oxygen and nutrient delivery to wound risk of hematoma formation edema à tension on wound risk of trauma proliferation, maturation proliferation hemostasis proliferation, maturation surgical materials suture material suture caliber strength of suture material inflammatory reaction from suture material ¯ caliber à ¯ strength inflammation infection persistent inflammatory phase, prevents proliferation and maturation of wound inflammation setting of procedure greater risk of infection in inpatients vs. outpatients inflammation skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 597 bleeding active bleeding hematoma prevents progression to normal wound healing tension on wound hemostasis patient adherence lifestyle and occupational hazards (increased tension and rates of infection) gender rate of dehiscence: males > females genetic diseases disorders of collagen formation disorders of coagulation impaired collagen production during wound healing inability to coagulate à persistent bleeding, risk of hematoma formation proliferation, maturation hemostasis patient age young age old age active lifestyle ¯ collagen production proliferation, maturation atherosclerosis diabetes hypertension hyperglycemia ® atherosclerosis ® ¯ blood flow oxidative stress, perivascular inflammation, fibrosis, and arterial calcification ® atherosclerosis ® ¯ blood flow proliferation proliferation skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 598 smoking ¯ chemokines, ¯ chemoattractants oxidative stress, perivascular inflammation, ¯ clotting ® ¯ blood flow ¯ protease inhibition, impaired collagen synthesis ® ¯ collagen inflammation proliferation proliferation, maturation obesity ¯ o2 supply, o2 demand ® hypoxia ® impaired immune response, ¯ collagen formation inflammation, proliferation malnutrition ¯ nutrient availability ® impaired wound healing hemostasis, inflammation, proliferation, maturation medications isotretinoin immunosuppressants nsaids impaired collagen and noncollagen protein synthesis ® ¯ collagen suppression of dermal and epidermal genes ® ¯ il signaling, cytoskeleton remodeling, keratinocyte proliferation ¯ pge2, pgd2, vegf® impaired keratinocyte proliferation, ¯ angiogenesis, ¯ granulation tissue proliferation, maturation proliferation inflammation, proliferation conflict of interest disclosures: none funding: none skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 599 corresponding author: andrew m. armenta, m.d. 301 university blvd 4.122, mccullough galveston, tx 77550-0783 email: amarment@utmb.edu references: 1. guy gp, machlin sr, ekwueme du, yabroff kr. prevalence and costs of skin cancer treatment in the u.s., 2002-2006 and 2007-2011. am j prev med. feb 2015;48(2):183-187. 2. wang dm, morgan fc, besaw rj, schmults cd. an ecological study of skin biopsies and skin cancer treatment procedures in the united states medicare population, 2000 to 2015. j am acad dermatol. 2018. 78(1):47-53. 3. rosen r, manna b. statpearls. wound dehiscence. statpearls publishing; 2020. 4. basu p, goldenberg a, cowan n, eilers r, hau j, jiang sib. a 4-year retrospective assessment of postoperative complications in immunosuppressed patients following mohs micrographic surgery. j am acad dermatol. jun 2019;80(6):1594-1601. 5. alam m, ibrahim o, nodzenski m, et al. adverse events associated with mohs micrographic surgery: multicenter prospective cohort study of 20,821 cases at 23 centers. jama dermatol. dec 2013;149(12):1378-85. 6. steinman hk, clever h, dixon a. the characteristics of mohs surgery performed by dermatologists who learned the procedure during residency training or through postgraduate courses and observational preceptorships. proc (bayl univ med cent). apr 2016;29(2):119-23. 7. wallace h, basehore b, zito p. statpearls. wound healing phases. statpearls publishing; 2020. 8. gonzalez ac, costa tf, andrade za, medrado ar. wound healing a literature review. an bras dermatol. 2016 sep-oct 2016;91(5):614620. 9. ireton je, unger jg, rohrich rj. the role of wound healing and its everyday application in plastic surgery: a practical perspective and systematic review. plast reconstr surg glob open. 2013;1(1):e10-e19. 10. carlson ma. acute wound failure. surg clin north am. jun 1997;77(3):607-36. 11. gabrielli f, potenza c, puddu p, sera f, masini c, abeni d. suture materials and other factors associated with tissue reactivity, infection, and wound dehiscence among plastic surgery outpatients. plast reconstr surg. jan 2001;107(1):38-45. 12. merritt bg, lee ny, brodland dg, zitelli ja, cook j. the safety of mohs surgery: a prospective multicenter cohort study. j am acad dermatol. dec 2012;67(6):1302-9. 13. cook jl, perone jb. a prospective evaluation of the incidence of complications associated with mohs micrographic surgery. arch dermatol. feb 2003;139(2):143-52. 14. falland-cheung l, scholze m, lozano pf, et al. mechanical properties of the human scalp in tension. j mech behav biomed mater. 08 2018;84:188-197. 15. buka b, uliasz a, krishnamurthy k. buka's emergencies in dermatology. springer; 2013. 16. paul sp. biodynamic excisional skin tension lines for surgical excisions: untangling the science. ann r coll surg engl. apr 2018;100(4):330-337. 17. maranda el, heifetz r, cortizo j, hafeez f, nouri k. kraissl lines—a map. jama dermatol. 2016;152(9):1014. 18. stasko t, roenigk h, jr rh. complications of cutaneous procedures. in: dermatologic surgery: principles and practice, 2nd ed,. new york: marcel dekker; 1996. p. 149. 19. berens am, akkina sr, patel sa. complications in facial mohs defect reconstruction. curr opin otolaryngol head neck surg. aug 2017;25(4):258-264. 20. alghamdi km. the gliding stitch. dermatol surg. jun 2008;34(6):803-5. 21. giandoni mb, grabski wj. surgical pearl: the dermal buried pulley suture. j am acad dermatol. jun 1994;30(6):1012-3. 22. casparian jm, monheit gd. surgical pearl: the winch stitch-a multiple pulley suture. j am acad dermatol. jan 2001;44(1):114-6. 23. coldiron bm. closure of wounds under tension. the horizontal mattress suture. arch dermatol. sep 1989;125(9):1189-90. 24. breuninger h, keilbach j, haaf u. intracutaneous butterfly suture with absorbable synthetic suture material. technique, tissue reactions, and results. j dermatol surg oncol. jul 1993;19(7):607-10. 25. clayton a, stasko t. dermatology. 3rd ed. vol 2. surgical complications and optimizing outcomes elsevier; 2012. 26. wahie s, lawrence cm. wound complications following diagnostic skin biopsies in dermatology inpatients. arch dermatol. oct 2007;143(10):1267-71. skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 600 27. sandy-hodgetts k, carville k, leslie gd. determining risk factors for surgical wound dehiscence: a literature review. int wound j. jun 2015;12(3):265-75. 28. delpachitra mr, heal c, banks j, divakaran p, pawar m. risk factors for surgical site infection in minor dermatological surgery: a systematic review. adv skin wound care. may 2019;32(5):217-226. 29. gantwerker ea, hom db. skin: histology and physiology of wound healing. facial plast surg clin north am. aug 2011;19(3):441-53. 30. reimer a, has c. [syndromes with skin fragility]. hautarzt. jul 2019;70(7):481-489. 31. libby p, buring je, badimon l, hansson gk, deanfield j, bittencourt ms, tokgözoğlu l, lewis ef. atherosclerosis. nat rev dis primers. 2019 aug 16;5(1):56. 32. barchitta m, maugeri a, favara g, et al. nutrition and wound healing: an overview focusing on the beneficial effects of curcumin. int j mol sci. mar 2019;20(5). 33. guzik tj, touyz rm. oxidative stress, inflammation, and vascular aging in hypertension. hypertension. 10 2017;70(4):660667. 34. sørensen lt. wound healing and infection in surgery: the pathophysiological impact of smoking, smoking cessation, and nicotine replacement therapy: a systematic review. ann surg. jun 2012;255(6):1069-79. 35. siasos g, tsigkou v, kokkou e, et al. smoking and atherosclerosis: mechanisms of disease and new therapeutic approaches. curr med chem. 2014;21(34):3936-48. 36. anderson k, hamm rl. factors that impair wound healing. j am coll clin wound spec. dec 2012;4(4):84-91. 37. wilson ja, clark jj. obesity: impediment to wound healing. crit care nurs q. 2003 apr-jun 2003;26(2):119-32. 38. wagner ij, szpalski c, allen rj, et al. obesity impairs wound closure through a vasculogenic mechanism. wound repair regen. 2012 julaug 2012;20(4):512-22. 39. casey g. nutritional support in wound healing. nurs stand. 2003 feb 19-25 2003;17(23):55-8. 40. russell l. the importance of patients' nutritional status in wound healing. br j nurs. mar 2001;10(6 suppl):s42, s44-9. 41. anderson b. nutrition and wound healing: the necessity of assessment. br j nurs. 2005 oct 27-nov 9 2005;14(19):s30, s32, s34. 42. shigematsu t, tajima s. modulation of collagen synthesis and cell proliferation by retinoids in human skin fibroblasts. j dermatol sci. mar 1995;9(2):142-5. 43. aksoy hm, aksoy b, çalikoglu e. systemic retinoids and scar dehiscence. indian j dermatol. 2019 jan-feb 2019;64(1):68-70. 44. van anholt rd, sobotka l, meijer ep, et al. specific nutritional support accelerates pressure ulcer healing and reduces wound care intensity in non-malnourished patients. nutrition. sep 2010;26(9):867-72. 45. brewer jd, otley cc, christenson lj, phillips pk, roenigk rk, weaver al. the effects of sirolimus on wound healing in dermatologic surgery. dermatol surg. feb 2008;34(2):216-23. 46. shanmugam vk, fernandez sj, evans kk, et al. postoperative wound dehiscence: predictors and associations. wound repair regen. 2015 mar-apr 2015;23(2):184-90. 47. zhao-fleming h, hand a, zhang k, et al. effect of non-steroidal anti-inflammatory drugs on postsurgical complications against the backdrop of the opioid crisis. burns trauma. 2018;6:25. 48. goren i, lee sy, maucher d, et al. inhibition of cyclooxygenase-1 and -2 activity in keratinocytes inhibits pge. int wound j. feb 2017;14(1):53-63. 49. otley cc, fewkes jl, frank w, olbricht sm. complications of cutaneous surgery in patients who are taking warfarin, aspirin, or nonsteroidal anti-inflammatory drugs. arch dermatol. feb 1996;132(2):161-6. 50. billingsley em, maloney me. intraoperative and postoperative bleeding problems in patients taking warfarin, aspirin, and nonsteroidal antiinflammatory agents. a prospective study. dermatol surg. may 1997;23(5):381-3; discussion 384-5. personal protective equipment (ppe), handwashing and sanitizers cause skin disorders in up to 63% of healthcare workers1 raising interest in topical agents that enhance skin barrier function. subject protocols were designed to evaluate the barrier function of rx medical device creams with in vitro tests. a dye test found a rx tri-lipid emollient was twice as effective as a rx dimethicone. the tri-lipid emollient also blocked microbial passage through a filter barrier test. clinical studies are warranted to demonstrate potential benefits of rx lipid-based emollients to improve skin barrier function in the covid-19 era. synopsis improving skin barrier function during the covid-19 era: laboratory studies of a prescription tri-lipid emollient garrett campbell, ryan hartung, phd, jared churko, phd & david thorpe, md, phd personal protective equipment (ppe) and stringent hygienic practices of this covid-19 era often cause skin irritation, cracks, dryness, irritant contact dermatitis & other lesions, and raise concerns about skin colonization, nosocomial infections, safety and compliance of personnel because of compromised skin barrier function. up to 63% of healthcare workers are affected by such skin disorders.1 a recent study of 270 healthcare workers caring for covid-19 patients in an irish hospital found that 82.6% had dermatitis.2 among these frontline workers, 45% denied using emollients. the objective was to evaluate the barrier function of rx medical device creams with in vitro laboratory tests. that is, determine if medical device creams can enhance barrier function. introduction / objective pictures sourced from: lee h.c., goh c.l. occupational dermatoses from personal protective equipment during the covid-19 pandemic in the tropics – a revew. eur acad derm & ven. 2020 in press. gouin j-p, kiecolt-glaser jk. the impact of psychological stress on wound healing: methods and mechanisms. immunol allergy clin north am. 2011;31(1):81-93. materials the first skin barrier protection product was rx tri-lipid emollient epiceram® comparator product was a dimethicone prescription cream commonly used in u.s. hospitals. 12-layer gauze was 2 x 2 inch equatetm gauze pads used in dye-test. whatman no. 5 filter paper with average pore size of 10 microns used in microbe test. 2 gram (+) bacteria, staphylococcus aureus and staphylococcus epidermidis, and 2 gram (-) organisms, e. coli and serratia marcescens; 2 motile and 2 immotile species. some are skin-related microbes. method: principle & enhanced barrier dye drop test principle. standard protocols used by the fda to substantiate wound dressing barrier function3 were adapted to evaluate the physical barrier effects of skin creams. per these protocols, there are two key tests of in vitro barrier function: one uses dye and the other uses microbes to see if they can pass through a barrier dressing. in the case of dye, the variable of treating gauze with creams was added, and for the microbial test barrier gauze was replaced by filter paper. matrices of sterile gauze or filter paper were treated with creams or not, either freshly applied or allowed to dry for 2 hours at 30oc. dye drop test. for challenge of gauze by dye, 25 µls of 1% aqueous methylene blue were applied, allowed to soak through the gauze for 30 minute, and the number of layers stained were photographed and counted. interpretation: dye penetrating fewer layers represents greater barrier function (protection). illustration of the “dye drop test” used to demonstrate the blocking function of a barrier wound dressing (b). untreated control results: enhanced barrier dye drop test sterile 2” x 2” gauze was treated with tri-lipid, comparator product, or nothing. dye was added & soaked for 30 min. then gauze was opened and photographed. tri-lipid comparator product results: untreated control gauze had the most stained layers & tri-lipid cream had the fewest layers stained. dimethicone comparator differed from the others. method: microbial barrier filter test part 1 goal. determine how much time is sufficient to allow microbes to move through a porous filter paper matrix and reach the surface of an agar plate. step 1. filter paper was placed onto agar ensuring no air was trapped. the filter was thoroughly wetted by the agar medium and warmed to 30oc. step 2. at different times (t minus 2 h, 1.5 h, 1 h, 0.5 h, 15 min & 5 min) a standardized loop-full amount of each microbial species was placed on top of the filter paper. counting down, at time zero the filter paper was removed ending the transit of any other microbes to the surface of the agar. step 3. the plates were incubated at 30oc x 36 h. microbes that passed through the filter paper grew into a mass of confluent colonies. this biomass area was measured. analysis. sketchandcalc (icalc inc.) was used to calculate the surface area of growth. semi-quantitatively, the area is proportional to the numbers of microbes that passed through the filter paper, and this time dependence was determined. part 2 goal. next, determine whether a cream can make the filter paper impervious to the passage of microbes. step 1. filter paper was cut into half circles. for treated filter paper, cream was applied and spread uniformly using a glass slide and dried for 2 h at 30oc. untreated filter paper was used as a control. step 2. filter papers were placed onto agar and microbes were added as before. after incubation for 2 h at 30oc, the filter papers were removed. step 3. the plates were incubated at 30oc x 36 h. microbes that passed through the filter paper grew into a mass of confluent colonies. plates were photographed and results were recorded. interpretation: no growth is proof of complete blockage of microbial passage through treated filter papers. such a result was scored as passing the microbial barrier filter test. illustration of microbial barrier filter test filter papers were treated with cream or not1 both the �lter with cream and the untreated �lter were then applied to petri plates 2 a loop-full of challenge bacteria were then applied to the treated or intreated �lter paper 3 after 2 hours the �lters were removed and plates were incubated plates were incubated for bacterial growth the plates were recorded for signes of growth on either the treated or untreated sides of the dish 4 5 6 results: microbial barrier filter test – part 1 measured biomass area is related to time of exposure of microbes on filter. the motile species penetrated faster than immotile species. 30 minutes of exposure to the untreated, control filter paper was sufficient for all tested species to reach the agar surface. providing exposures of 90 minutes to 2 hours assured a good challenge of barrier function of applied creams. 4 106.29mm2 3 87.6mm2 results: microbial barrier filter test – part 2 agar plate side c: control filter paper without cream agar plate side e: dried tri-lipid emollient filter paper top to bottom: serratia, s. epidermidis, s. aureus & e. coli. result: tri-lipid passes microbial barrier filter test repeated 4 times conclusions limitations. variety of microbes & creams tested were limited. these in vitro experiments demonstrate that a prescription tri-lipid emollient provided a physical barrier to passage through matrices when challenged by methylene blue dye and four different microbes. the proprietary 3:1:1 tri-lipid emollient had twice the barrier function as a common hospital prescription dimethicone cream in the in vitro barrier dye drop test. clinical studies are warranted to demonstrate potential benefits of rx lipid-based emollients to improve skin barrier function in the covid-19 era. readily available methods are shown to evaluate barrier function of skin creams in vitro, and positive findings are timely during the covid-19 pandemic. references 1. lee h.c., goh c.l. occupational dermatoses from personal protective equipment during the covid-19 pandemic in the tropics – a revew. eur acad derm & ven. 2020 in press. 2. kiely lf, moloney e, o’sullivan g, eustace ja, gallagher j, bourke jf. irritant contact dermatitis in healthcare workers as a result of the covid-19 pandemic: a cross-sectional study. clin exp dermatol. published online july 23, 2020. doi:10.1111/ced.14397 3. kitchel b. performance claims and supporting test methods, a subsection of general and plastic surgery devices panel of the medical devices advisory committee. published online september 20, 2016:37-55. disclosure: all authors are paid consultants, and the work was supported by primus pharmaceuticals, inc 0 1 2 3 4 5 6 7 8 9 10 untreated control rx tri-lipid cream rx dimethicone cream median layers of gauze stained by dye all comparisons p<0.01, t-test, n=4 kristian reich, md1; mark goodfi eld, md2; lawrence green, md3; kristine nograles, md4; eugenia levi, pharmd4; richard g.b. langley, md5 1dermatologikum hamburg and sciderm research institute, hamburg, germany; 2leeds general infi rmary, leeds, uk; 3george washington university school of medicine, washington, dc; 4celgene corporation, summit, nj; 5dalhousie university, halifax, ns, canada introduction • psoriasis is a chronic, systemic infl ammatory disease affecting 1% to 4% of the world’s population.1-3 • currently available therapies are often compromised by adverse events (aes), safety and tolerability issues, and route of administration (injection/infusion vs. oral).4 • apremilast, an oral, small-molecule phosphodiesterase 4 inhibitor, works intracellularly within immune cells to regulate the production of infl ammatory mediators.5 • apremilast was approved by the us food and drug administration and by the european commission for treatment of psoriasis and psoriatic arthritis. • evaluation in a placebo-controlled study of oral apremilast and etanercept in plaque psoriasis (liberate; nct01690299) is a global phase 3b study of apremilast 30 mg twice daily (apr) or etanercept 50 mg once weekly (etn), compared with placebo (pbo) for the treatment of biologic-naive patients with moderate to severe plaque psoriasis. • the objective of the current analysis was to explore the effi cacy of apr and etn in patients for 16 weeks and through 104 weeks of the liberate study. methods patients key inclusion criteria • adults ≥18 years of age with chronic plaque psoriasis for ≥12 months who were candidates for phototherapy and had no prior exposure to biologics for the treatment of psoriatic arthritis or psoriasis • moderate to severe plaque psoriasis, as defi ned by psoriasis area and severity index (pasi) score ≥12, psoriasis-involved body surface area (bsa) ≥10%, and static physician global assessment (spga) score ≥3 • inadequate response, inability to tolerate, or contraindication to ≥1 conventional systemic agent for the treatment of psoriasis key exclusion criteria • prior treatment with >3 systemic agents for the management of psoriasis • other clinically signifi cant or major uncontrolled diseases; serious infections, including latent, active, or history of incompletely treated tuberculosis study design • there were 2 treatment phases: a 16-week randomized, double-blind, pbo-controlled phase and an 88-week apr extension phase (overall treatment duration, 104 weeks; figure 1). at week 16, patients in the pbo and etn groups switched to apr, and patients in the apr group continued apr. apr was maintained from weeks 16 to 104 (apr extension phase). figure 1. study design follow-up phase 4 weeks week ‒5 week 16 primary end point week 32 topicals/phototherapy* for non-responders week 104week 0 apremilast extension phase placebo-controlled phase screening period etanercept 50 mg qw + placebo tablets dose titration apremilast 30 mg bid + placebo injection apremilast 30 mg bid apremilast 30 mg bid apremilast 30 mg bid no dose titration placebo tablets + placebo injection ra n d o m iz e (1 :1 :1 ) screening note: liberate was not powered for apr vs. etn comparisons. *starting at week 32, all non-responders (<pasi-50) had the option of adding topical therapies and/or ultraviolet b phototherapy (excluding oral psoralen combined with ultraviolet a) to their treatment regimen. two patients in each group received topical therapy and/or phototherapy. bid=twice daily; pasi-50=≥50% reduction from baseline in psoriasis area and severity index score; qw=once weekly. statistical analysis • effi cacy assessments were conducted for the pbo-controlled phase in the modifi ed intent-to-treat (mitt) population (all randomized patients who received ≥1 dose of study medication and had both baseline pasi and ≥1 post-treatment pasi evaluations); week 104 analyses included patients who entered the apr extension phase and were treated in the phase. • the safety population consisted of all patients who were randomized and received ≥1 dose of study medication. • continuous end points were evaluated using an analysis of covariance model with treatment and baseline body mass index (bmi; <30 and ≥30 kg/m2) as factors and baseline value as a covariate. • missing values were imputed using the last-observation-carried-forward (locf) methodology. results • demographic and baseline characteristics were generally well balanced between treatment groups (table 1). table 1. baseline patient demographic and disease characteristics pbo n=84 apr n=83 etn n=83 age, mean, years 43.4 46.0 47.0 male, n (%) 59 (70.2) 49 (59.0) 49 (59.0) bmi, mean, kg/m2 29.54 29.15 29.86 weight, mean, kg 89.51 88.52 88.08 duration of psoriasis, mean, years 16.6 19.7 18.1 pasi score (0–72), mean 19.4 19.3 20.3 pasi score >20, n (%) 32 (38.1) 28 (33.7) 34 (41.0) bsa, mean, % 27.3 27.1 28.4 bsa >20%, n (%) 42 (50.0) 45 (54.2) 47 (56.6) napsi score ≥1, n (%) 46 (54.8) 52 (62.7) 50 (60.2) napsi score*, mean (sd) 4.1 (1.9) 4.2 (2.0) 4.3 (2.2) scpga ≥3, n (%) 58 (69.0) 54 (65.1) 54 (65.1) prior use of conventional systemic medications, n (%)§ 70 (83.3) 66 (79.5) 58 (69.9) *in patients with napsi ≥1 for target nail, representing worst nail psoriasis at baseline. §no prior exposure to biologic therapy for treatment of psoriatic arthritis or psoriasis. napsi=nail psoriasis severity index; scpga=scalp physician global assessment. results (cont’d) effi cacy pasi-75 response • at week 16, a ≥75% reduction from baseline in pasi score (pasi-75) was achieved by signifi cantly more patients receiving apr vs. pbo (p<0.0001) (figure 2). • the pasi-75 response achieved at week 16 was sustained through week 104 in patients continuing apr or switching from etn to apr at week 16 (figure 2). figure 2. percentage of patients achieving pasi-75 response (mitt, locf) 11.9 * 39.8 * 48.250.7 45.9 51.9 0 20 40 60 80 100 34/74 week 104 40/83 week 16 41/79 week 104 pa tie nt s ac hi ev in g pa si -7 5§ (% ) n/m = pbo pbo/apr apr etn apr/apr etn/apr 33/83 week 16 10/84 week 16 37/73 week 104 *p<0.0001 vs. pbo. §response at week 16 and week 104 was determined using the locf methodology. the analysis for week 16 includes all patients in the modifi ed intent-to-treat (mitt) group, while the week 104 analysis includes patients who entered the apremilast extension phase and were treated in the phase. error bars indicate 2-sided 95% confi dence intervals. dlqi total score ≤5 (minimal impairment) • at week 16, across treatment groups, 53.4% to 65.0% of patients achieved a dlqi score ≤5 (p=ns vs. pbo) (figure 3). • at week 104, dlqi ≤5 was achieved by 66.0% to 72.5% of patients across treatment groups (figure 3). figure 3. percentage of patients achieving dlqi total score ≤5 (data as observed) pbo pbo/apr apr etn apr/apr etn/apr 53.4 62.0 65.0 66.7 72.5 66.0 0 20 40 60 80 100 29/40 week 104 52/80 week 16 33/50 week 104 pa tie nt s ac hi ev in g d lq i t ot al s co re ≤ 5* (% ) n/m = 44/71 week 16 39/73 week 16 34/51 week 104 *examined among all patients who had data at time of observation (i.e., completers, without imputation). error bars indicate 2-sided 95% cis. scalp and nail response • among patients with baseline scpga ≥3 (moderate or greater), scpga response of 0 (clear) or 1 (minimal) was achieved by signifi cantly more patients receiving apr compared with patients receiving pbo at week 16 (figure 4). • the scpga response achieved at week 16 was sustained through week 104 in apr/apr patients and etn/apr patients. responses at week 104 among pbo/apr patients were generally similar to those in apr/apr patients (figure 4). figure 4. percentage of patients achieving scpga response of 0 (clear) or 1 (minimal) (mitt, locf) pbo pbo/apr apr etn apr/apr etn/apr 25.9 * 44.4 § 50.0 50.0 59.2 56.6 0 20 40 60 80 100 29/49 week 104 27/54 week 16 30/53 week 104 pa tie nt s ac hi ev in g sc pg a re sp on se o f 0 o r 1‡ (% ) 24/54 week 16 15/58 week 16 25/50 week 104 n= *p=0.0458 vs. pbo. §p=0.0083 vs. pbo. ‡response at week 16 and week 104 was determined using the locf methodology. week 16 analyses included patients with baseline scpga score ≥3. week 104 analysis includes patients with scpga score ≥3 who entered the apr extension phase and were treated in the phase. error bars indicate 2-sided 95% confi dence intervals. • the proportions of patients with nail psoriasis at baseline (napsi ≥1) who achieved napsi-50 at week 16 were higher with apr (25.0%) or etn (48.0%) than pbo (10.9%; p=0.0701 vs. apr and p<0.0001 vs. etn). • at week 104, napsi-50 response was 60.4% (apr/apr), 65.2% (etn/apr), and 48.6% (pbo/apr) (figure 5). • the mean percentage change from baseline in napsi score continued to improve in apr/apr patients and was sustained in etn/ apr patients through week 104 (figure 5). results (cont’d) figure 5. mean percentage change in napsi score at week 16 and week 104 (mitt, locf) pbo pbo/apr apr etn apr/apr etn/apr –10.1 –18.7 * –37.7 § –48.1 –48.2 –51.1 –100 –80 –60 –40 –20 0 week 104 48 week 16 50 week 104 45 m ea n % c ha ng e fr om ba se lin e in n ap si s co re ‡ n= week 16 50 week 16 42 week 104 33 *p=0.4959 vs. pbo. §p=0.0024 vs. pbo. ‡in patients with napsi score ≥1 at baseline. includes all patients with a baseline value and a post-baseline value at the study week. missing scores were imputed using the locf methodology. the mean napsi score at baseline was 4.1 (pbo), 4.2 (apr), and 4.3 (etn). • no increase in incidence of adverse events (aes) occurring in ≥5% of patients in the pbo-controlled period was observed among patients in the apr/apr group with long-term exposure to apr. • all cases of diarrhea and nausea occurring in the apr extension phase (table 2) were mild or moderate in severity and generally resolved within 1 month. table 2. adverse events in ≥5% of patients in any treatment group patients, n (%)*,§ apr extension phase (weeks 16 to 104) pbo/apr‡ apr/apr etn/apr|| n=73; pt-yrs=95.6 n=74; pt-yrs=89.4 n=79; pt-yrs=102.3 n (%) n (%) n (%) diarrhea 13 (17.8) 4 (5.4) 6 (7.6) nausea 5 (6.8) 3 (4.1) 5 (6.3) urti 5 (6.8) 5 (6.8) 1 (1.3) bronchitis 1 (1.4) 4 (5.4) 1 (1.3) nasopharyngitis 4 (5.5) 2 (2.7) 5 (6.3) headache 5 (6.8) 2 (2.7) 3 (3.8) sinusitis 0 (0.0) 1 (1.4) 5 (6.3) pain in extremity 1 (1.4) 3 (4.1) 4 (5.1) arthralgia 4 (5.5) 4 (5.4) 3 (3.8) rebound psoriasis 1 (1.4) 2 (2.7) 7 (8.9) psoriasis 2 (2.7) 4 (5.4) 0 (0.0) *each patient is counted once for each applicable category. §data are from patients who entered the apr extension phase and were treated in the phase. ‡no dose titration for apr. ||dose titration for apr. urti=upper respiratory tract infection. conclusions • apr demonstrated signifi cant effi cacy vs. pbo at week 16 that was sustained through week 104 in biologic-naive patients with moderate to severe plaque psoriasis. • apr and etn each demonstrated statistically signifi cant improvements in scalp psoriasis compared with pbo at week 16 that were sustained through week 104. • improvements in qol achieved with apr and etn at week 16 (compared with pbo) were sustained through week 104. • improvements in nail psoriasis were achieved with apr at week 16, and continued apr treatment over 104 weeks resulted in further improvements in nail psoriasis. • effi cacy was maintained in etn patients who switched to apr. • ae rates did not increase with prolonged apr exposure, and no new safety or tolerability issues were observed through week 104 in patients with moderate to severe plaque psoriasis. references 1. helmick cg, et al. am j prev med. 2014;47:37-45. 2. rachakonda td, et al. j am acad dermatol. 2014;70:512-516. 3. parisi r, et al. j invest dermatol. 2013;133:377-385. 4. schmitt j, et al. br j dermatol. 2008;159:513-526. 5. schafer ph, et al. cell signal. 2014;26:2016-2029. acknowledgments the authors acknowledge fi nancial support for this study from celgene corporation. the authors received editorial support in the preparation of this poster from amy shaberman, phd, of peloton advantage, llc, parsippany, nj, usa, funded by celgene corporation, summit, nj, usa. the authors, however, directed and are fully responsible for all content and editorial decisions for this poster. correspondence kristian reich – kreich@dermatologikum.de disclosures kr: abbvie, amgen, biogen, boehringer ingelheim, celgene corporation, centocor, covagen, eli lilly, forward pharma, glaxosmithkline, janssencilag, leo pharma, medac, merck sharp & dohme, novartis, ocean pharma, pfi zer (wyeth), regeneron, takeda, ucb pharma, and xenoport – consultant, advisory board member, speaker, and investigator. mg: has no confl icts of interest to disclose. lg: abbvie, amgen, celgene corporation, leo pharma, novartis, pfi zer, and valeant – investigator and/or speaker and/or consultant. kn & el: celgene corporation – employment. rgbl: abbvie, amgen, celgene corporation, eli lilly, leo pharma, merck, novartis, and pfi zer – advisory board member and/or paid speaker and/or participated in clinical trials. presented at: the 2017 fall clinical dermatology conference; october 12–15, 2017; las vegas, nv. safety and efficacy of apremilast through 104 weeks in patients with moderate to severe psoriasis who continued on apremilast or switched from etanercept treatment in the liberate study fc17postercelgenereichsafetyefficacyliberatestudy.pdf objective • this post hoc analysis of two randomized phase 3 trials (nct02462070 and nct02462122)1 and a 52-week open-label study (nct02462083)2 evaluated the efficacy and safety of halobetasol propionate (0.01%) and tazarotene (0.045%) lotion (hp/taz) in participants achieving ≥75% improvement in the product of investigator’s global assessment and affected body surface area (igaxbsa-75) at or before week 12 conclusions • hp/taz was associated with long-term skin clearance in participants who achieved clinically meaningful improvement in psoriasis lesions, as measured by igaxbsa-75 – these findings suggest that hp/taz promotes remission of psoriasis after treatment discontinuation • clinically meaningful improvement in psoriasis lesions was also associated with decreased signs and symptoms (itch, dryness, and burning/ stinging) and posttreatment maintenance of those improvements synopsis • fixed-combination halobetasol propionate (0.01%) and tazarotene (0.045%) lotion (hp/taz) is approved to treat plaque psoriasis in adults3 • the product of investigator’s global assessment and affected body surface area (igaxbsa) is a measure of psoriasis severity4 – ≥75% reduction from baseline (igaxbsa-75) is considered as clinically meaningful improvement in skin clearance5 methods • in the randomized trials, participants were assigned 2:1 to either hp/taz once daily or vehicle lotion, with a primary endpoint of treatment success at week 8 (iga score of clear [0] or almost clear [1]) and follow-up assessment at week 12 (figure 1a) • similarly, in the open-label study, all participants received hp/taz once daily for 8 weeks – those who achieved treatment success stopped treatment and were reevaluated monthly through 52 weeks, with retreatment as needed (any time iga was >1) – those who did not achieve treatment success at week 8 continued to apply hp/taz – participants were allowed 24 continuous weeks of hp/taz if they achieved ≥1-grade improvement in iga from baseline at week 12 (figure 1b) • in the randomized phase 3 trials, 276 participants were treated with hp/taz and 142 received vehicle, while a total of 550 participants were treated in the long-term open-label study • participants who achieved igaxbsa-75 at or before week 12 in the randomized phase 3 and open-label studies of hp/taz were included in the analysis • signs and symptoms of psoriasis were evaluated at each study visit – itch and stinging/burning were scored on a scale from 0 (none) to 3 (severe) as reported by the participant in the past 24 hours – dryness was scored on a scale from 0 (none) to 3 (severe) as assessed by the investigator figure 1. designs of (a) pivotal phase 3 and (b) open-label studies of hp/taz. hp/taz, halobetasol propionate (0.01%) and tazarotene (0.045%) lotion; iga, investigator’s global assessment. atreatment success defined as iga score of clear (0) or almost clear (1). bimprovement defined as ≥1-grade improvement from baseline iga; those demonstrating improvement continued the study and were subsequently managed in 4-week cycles (ie, treated with once-daily hp/taz if they did not achieve treatment success or received no treatment until the next evaluation if they achieved treatment success). maximum continuous exposure was 24 weeks. results efficacy participant characteristics • in a pooled analysis of the phase 3 trials, 140 of 276 participants (50.7%) treated with hp/taz and 19 of 142 participants (13.4%) who received vehicle achieved igaxbsa-75 by week 12 • in the open-label study, 254 of 550 participants (46.2%) achieved igaxbsa-75 by week 12 • across all studies, prevalence of moderate-to-severe symptoms at baseline was greater in hp/taz-treated participants compared with those receiving vehicle (table 1) table 1. baseline characteristics of participants in clinical studies of hp/taz who achieved igaxbsa-75 at or before week 12 igaxbsa-75 • in the randomized trials, a numerically greater proportion of participants receiving hp/taz achieved igaxbsa-75 versus those receiving vehicle at week 8 and week 12 (4 weeks posttreatment; figure 2) • in the open-label study, 63.3% of participants who achieved igaxbsa-75 by week 12 maintained igaxbsa-75 at week 52 figure 2. proportion of participants achieving igaxbsa-75 at week 8 and week 12 (4 weeks posttreatment) in the randomized phase 3 trials of hp/taz. bsa, body surface area; hp/taz, halobetasol propionate (0.01%) and tazarotene (0.045%) lotion; iga, investigator’s global assessment; igaxbsa-75, ≥75% improvement in product of iga and bsa. signs and symptoms of psoriasis • in the phase 3 randomized trials, most participants receiving hp/taz or vehicle who achieved igaxbsa-75 at or before week 12 also reported no itch (71.1% vs 73.7%), dryness (68.1% vs 78.9%), or burning/stinging (85.9% vs 94.7%) at week 8, with similar results at week 12 (4 weeks posttreatment; figure 3) figure 3. proportion of participants achieving igaxbsa-75 at or before week 12 who were free of itch, dryness, and burning/stinging at week 8 and week 12 (4 weeks posttreatment) in the randomized phase 3 trials of hp/taz. bsa, body surface area; hp/taz, halobetasol propionate (0.01%) and tazarotene (0.045%) lotion; iga, investigator’s global assessment; igaxbsa-75, ≥75% improvement in product of iga and bsa. • in the open-label study of hp/taz, the proportion of participants with moderate-to-severe itch, dryness, and stinging/burning decreased at week 52 from baseline (table 2) table 2. change in moderate-to-severe signs/symptoms of psoriasis in the open-label study of hp/taz safety • across all studies, rates of skin atrophy, striae, telangiectasias, and folliculitis were low • at week 12 in the randomized phase 3 trials, only 1 participant (0.7%) in the hp/taz group experienced skin atrophy, and all other reactions were absent • in the open-label study, rates of these skin reactions were absent in all participants at week 52 long-term safety and efficacy of fixed-combination halobetasol propionate and tazarotene lotion in patients with clinically meaningful improvement in plaque psoriasis andrew alexis,1 james del rosso,2 tina bhutani,3 kim papp,4 abby jacobson5 1department of dermatology, weill cornell medical college, new york, ny; 2jdr dermatology research/thomas dermatology, las vegas, nv; 3ucsf psoriasis and skin treatment center, san francisco, ca; 4probity medical research and k. papp clinical research, waterloo, ontario, canada; 5ortho dermatologics (a division of bausch health us, llc), bridgewater, nj acknowledgments: this study was sponsored by ortho dermatologics. medical writing support was provided by medthink scicom and funded by ortho dermatologics. ortho dermatologics is a division of bausch health us, llc. references: 1. stein gold et al. j am acad dermatol. 2018;79:287-293. 2. lebwohl et al. j eur acad dermatol venereol. 2021;35:1152-1160. 3. duobrii [package insert]. bausch health us, llc; 2019. 4. gottlieb et al. dermatology. 2019;235:348-354. 5. blauvelt et al. j drugs dermatol. 2019;18:297-299. presented at the fall clinical dermatology conference • october 21-24, 2021 • las vegas, nv, and virtual sponsored by ortho dermatologics, a division of bausch health us, llc. baseline parameter pooled randomized trials (hp/taz, n=140) pooled randomized trials (vehicle, n=19) open-label study (n=254) iga 3 119 (85) 19 (100) 221 (87) iga 4 21 (15) 0 33 (13) mean bsa, % (sd) 5.8 (2.9) 5 (2.2) 5.5 (2.7) moderate-to-severe itch 62 (44.3) 3 (15.8) 118 (46.5) moderate-to-severe dryness 41 (29.3) 3 (15.8) 109 (42.9) moderate-to-severe stinging/burning 23 (16.4) 3 (15.8) 36 (14.2) all values are n (%) except for mean bsa. bsa, body surface area; hp/taz, halobetasol propionate (0.01%) and tazarotene (0.045%) lotion; iga, investigator’s global assessment; igaxbsa-75, ≥75% improvement in product of iga and bsa; sd, standard deviation. 71.1 73.7 70.1 78.9 68.1 78.9 70.9 73.7 85.9 94.7 95.5 100 0 10 20 30 40 50 60 70 80 90 100 hp/taz at week 8 hp/taz, n=140 vehicle, n=19 vehicle at week 8 92n = 96 116 14 15 18 94 95 128 15 14 19 hp/taz at week 12 vehicle at week 12 sy m pt o m -f re e pa rt ic ip an ts , % itch dryness burning/stinging 82.1 73.173.7 68.4 0 10 20 30 40 50 60 70 80 90 100 week 8 week 12 (4 weeks posttreatment) hp/taz (n=140) pa rt ic ip an ts a ch ie vi ng ig a xb sa -7 5, % vehicle (n=19) n=115 n=14 n=98 n=13 randomized, double-blind, vehicle-controlled treatment study 1 (nct02462070) posttreatment follow-up (no treatment) baseline b a 2:1 week 12 hp/taz lotion (n=135) vehicle lotion (n=68) week 8 study 2 (nct02462122) 2:1 hp/taz lotion (n=141) vehicle lotion (n=74) 2:1 2:1 day 0 week 8 week 12 week 24 week 52screening once-daily hp/taz for 8 weeks evaluated for treatment success at week 8a success treatment stopped for 4 weeks no success continued once-daily hp/taz for 4 weeks evaluated for improvement at week 12b no improvement discontinued from study • • if 24 weeks of continuous treatment were received at any point in the study and the participant did not achieve an iga score of 0 or 1, the participant was discontinued from the study. treatment stopped for 4 weeks continued once continued study and managed in 4 1 year, with participants reevaluated every 4 weeks for treatment success -week cycles for up to success: no success: daily hp/taz for 4 weeks sign/symptom participants with sign/symptom at week 52, n (%) mean change from baseline sd itch 10 (10.2) -0.70 1.09 dryness 6 (6.1) -0.70 0.90 stinging/burning 4 (4.1) -0.20 0.68 hp/taz, halobetasol propionate (0.01%) and tazarotene (0.045%) lotion; sd, standard deviation. powerpoint presentation integrating the 31-gene expression profile and clinicopathologic data to determine the risk of sentinel lymph node positivity and recurrence-free survival in cutaneous melanoma background methods › the 31-gene expression profile (31-gep) test for cutaneous melanoma assesses the risk of sentinel lymph node biopsy (slnb) positivity and regional recurrence, distant metastasis, and melanoma-specific survival (mss) using the primary tumor genetic profile.1-10 › slnb has a more than 80% negativity rate, and many patients with a negative slnb experience disease recurrence or death.11,12 acknowledgments & disclosures references › we would like to thank the patients and clinicians who received test results through castle. › this study was sponsored by castle biosciences, inc. › bm, aq, cb, and kc are employees and shareholders of castle biosciences, inc.. ew and jv are on the speaker’s bureau for castle biosciences, inc. nt has no conflicts. 1. gerami, p. et al. clin cancer res 2015. 21 (1) 175-183 2. keller, j. et al. cancer med 2019. 8 (5) 2205-2212. 3. zager, j. et al. bmc cancer 2018. 18 (1) 130. 4. whitman, e. et al. jco po 2021. (5) 1466-1479. 5. hsueh, e. et al. jco po 2021. 5 589-601. 6. podlipnik, s. et al. jeadv 2019. 33 (5) 857-862. 7. arnot, s. et al. ajs 2021. 8. dillon, l. et al. skin 2018. 2 (2) 111–121. 9. gastman, b. et al. jaad 2019. 80 (1) 149-157.e4. 10. gastman, b. et al. head & neck 2019. 41 (4) 871-879. 11. chen, j. et al. oncotarget 2016. 7 (29) 45671-45677. 12. morton, d. et al. nejm 2014. 370 (7) 599-609. results presented at the 2021 fall clinical dermatology conference in las vegas, nv; october 21-24, 2021. brian martin1, nicholas taylor2, eric whitman3, ann quick1, christine bailey1, kyle covington1, john vetto4 1castle biosciences, inc., friendswood, tx, 2zitelli and broadland, p.c., pittsburgh, pa, 3atlantic heath system cancer care, morristown, nj, 4oregon health & science university, portland, or. objective › the purpose of this study was to demonstrate the combined ability of two independently validated algorithms that incorporate the 31-gep with clinicopathologic features to predict individual slnb positivity risk and recurrence-free survival (rfs). › the i31-gep for slnb identified 31.2% (135/433) of patients with a <5% likelihood of sln positivity and these patients had high survival rates, showing that these patients could safely forego slnb. › in the sln negative population, 20% of patients identified as high risk by the i31-gep result and had 5year rfs rates that were identical to patients with stage iii disease (47.7% vs. 48.7%, respectively). › overall, using nccn treatment recommendations, the i31-gep test identified 44.8% (194/433) of patients who could have avoided slnb or were re-stratified as low or high risk compared to sln status alone. › the i31-gep can stratify patients with stage iib-iic melanoma according to risk of recurrence or distant metastasis. › using the combined i31-gep integrated approach can identify patients who may potentially forego slnb and those with high and low risk of recurrence for more personalized patient care decisions. conclusions › using artificial intelligence techniques, an algorithm to determine the individual likelihood of sln positivity was developed from 1398 cases and validated in an independent cohort of 1674 cases (i31-gep-slnb). next, a separate algorithm for personalized survival predictions for rfs, dmfs, and mss was developed from 1581 cases and validated in an independent cohort of 523 cases (i31-gep-outcomes). based on the available data, 98% of patients in the validation cohort did not receive pd-1, ctla-4, or braf/mek adjuvant therapy. › to create risk cut-points that align with nccn treatment recommendations, the midpoints between stage iia and iib was set as the risk cut-off (rfs: 69.8%; dmfs: 82.6%). those with an i31-gep-outcomes predicted rfs or dmfs higher than the cut-off were classified as low risk. otherwise, they were classified as high risk. › to evaluate the prognostic value of using both i31-gep algorithms, the subset of patients (n=433) not utilized in the development of either algorithm was analyzed first by i31-gepslnb, followed by i31-gep-outcomes. scan or click here for more info figure 3. five-year rfs and dmfs for patients with stage iib-iic disease. . figure 2. five-year rfs for patients stratified by i31-gep risk groups in sln negative and positive patient populations. sln positivity risk have good outcomes based on kaplan-meier analysis and were not evaluated further in this study. patients with at least 5% sln risk were analyzed by the i31-gep algorithm for outcomes to identify high and low risk patients. dmfs: distant metastasis-free survival. › data includes only patients with at least 5% sln positivity risk by i31-gep slnb (n=298), › dmfs (not shown) was also significantly stratified by the i31-gep for outcomes. › data taken from total cohort (n=433). all patients with stage iib-iic disease received higher than 5% sln positivity risk by the i31-gep for slnb. figure 1. analysis protocol. all patients received i31-gep for slnb. patients with <5% https://castlebiosciences.com/research-development/publications/ poster presented at the 37th fall clinical dermatology conference | las vegas, nv | october 18-21, 2018 shortand long-term efficacy and safety of glycopyrronium cloth for the treatment of primary axillary hyperhidrosis: post hoc pediatric subgroup analyses from the phase 3 studies adelaide a. hebert,1 dee anna glaser,2 lawrence green,3 william p. werschler,4 douglass w. forsha,5 janice drew,6 ramanan gopalan,6 david m. pariser7 1uthealth mcgovern medical school, houston, tx; 2saint louis university, st. louis, mo; 3george washington university school of medicine, washington, dc; 4premier clinical research, spokane, wa; 5jordan valley dermatology and research center, west jordan, ut; 6dermira, inc., menlo park, ca; 7eastern virginia medical school and virginia clinical research, inc., norfolk, va introduction • hyperhidrosis, a condition characterized by sweat production exceeding that which is necessary to maintain normal thermal homeostasis, has an estimated us prevalence of 4.8% (~15.3 million people)1 – in an online survey, 17.1% of us teens reported experiencing excessive sweating2 • hyperhidrosis is largely undertreated and underdiagnosed, particularly among pediatric patients1,3,4 • glycopyrronium tosylate (gt) is a topical anticholinergic recently approved by the us food and drug administration for primary axillary hyperhidrosis in patients ≥9 years of age (glycopyrronium cloth, 2.4%, for topical use)5 • gt improved disease severity, reduced sweat production, and improved quality of life in patients evaluated in two randomized, double-blind phase 3 studies for primary axillary hyperhidrosis (atmos-1 [nct02530281] and atmos-2 [nct02530294]), and in the open-label study (arido [nct02553789])6-8 • atmos-1 and atmos-2 were the first randomized, controlled phase 3 trials in primary axillary hyperhidrosis to enroll pediatric patients objective • evaluate the shortand long-term efficacy of gt in pediatric patients (≥9 to ≤16 years) versus the older subgroup (>16 years) in a pooled post hoc analysis methods study design and patients • atmos-1 (nct02530281; sites in the us and germany) and atmos-2 (nct02530294; us sites only) were parallelgroup, 4-week, double-blind, phase 3 clinical trials – patients were randomized 2:1 to gt or veh once daily (figure 1) – eligible patients were ≥9 years of age (only patients aged ≥18 years were recruited at german sites), had primary axillary hyperhidrosis for ≥6 months, gravimetrically-measured sweat production of ≥50 mg/5 min in each axilla, axillary sweating daily diary (asdd) sweating severity (item 2) score ≥4, and hyperhidrosis disease severity scale (hdss) ≥3 • arido was a 44-week, open-label extension of atmos-1 (nct02530281) and atmos-2 (nct02530294) – patients who completed atmos-1/atmos-2 with ≥80% treatment compliance were eligible to continue into arido and receive open-label gt for up to 44 additional weeks or until early termination (study terminated once the study objective of 100 patients receiving treatment for ≥12 months was achieved; figure 1) figure 1. atmos-1/atmos-2 and arido study design wk 0 randomization screening follow-up atmos-1 and atmos-2 arido randomized, double-blind treatment 44-week open-label extension patients aged ≥9 years with primary axillary hyperhidrosisa • ≥6 months duration • sweat production of ≥50 mg/5 min in each axilla • asdd item 2 score ≥4 • hdss grade 3 or 4 gt (n=229 | 234) gt 564 (86.6%) patients continued into arido vehicle (n=115 | 119) wk 4/etb wk 48 wk 49 co-primary efficacy endpoints at week 4: • asdd/asdd-c item 2 responder rate (≥4-point improvement) • absolute change in axillary sweat productionc secondary efficacy endpoints at week 4: • hdss responder rate (≥2-grade improvement) • sweat productionb response rate (≥50% reduction) other efficacy assessments at week 4: • change from baseline in cdlqi/dlqi atrial sites in the u.s. and germany bend of treatment for atmos-1 and atmos-2 cgravimetrically-measured asdd, axillary sweating daily diary; asdd-c, asdd-children; cdlqi, children’s dlqi; dlqi, dermatology life quality index; gt, topical glycopyrronium tosylate; hdss, hyperhidrosis disease severity scale; wk, week assessments • for the double-blind trials, coprimary efficacy endpoints were asdd item 2 (sweating severity) responder rate (≥4-point improvement from baseline), a newly developed patient-reported outcome,9 and absolute change from baseline in axillary gravimetric sweat production at week 4 – a child-specific version of the asdd (asdd-c) was utilized for patients ≥9 to <16 years – the asdd/asdd-c item 2 is a numeric rating scale (0 to 10) for assessing axillary sweating severity that has demonstrated validity, reliability and responsiveness to axillary hyperhidrosis treatment effect in clinical trials4 • for the open-label extension, the primary outcome was evaluation of long-term safety – safety was evaluated via treatment-emergent adverse events (teaes) through week 45 (week 44 + 1-week safety follow-up) and local skin reactions (lsrs) through week 44 – teaes are summarized from the first application of study drug in arido to week 45 – descriptive efficacy assessments were evaluated in arido at week 44 and relative to baseline of atmos-1/atmos-2 (up to 48 weeks of gt) and were an extension of select atmos-1/atmos-2 endpoints • gravimetrically-measured sweat production • hdss responder rate (≥2-grade improvement) • dermatology life quality index (dlqi; patients >16 years) and children’s dlqi (cdlqi; patients ≤16 years) analyses • this post hoc analysis evaluated pooled efficacy data according to patient age subgroups based on the dlqi and cdlqi, which have rigid age cutoffs for questionnaire administration – as such, the pediatric subgroup was defined to include patients ≥9 to ≤16 years and the older subgroup included patients >16 years – all efficacy and safety assessments were made in accordance with these subgroup definitions – as asdd/asdd-c item 2 was psychometrically evaluated and validated, the standard age cutoffs (asdd, ≥16 years; asdd-c <16 years) for questionnaire administration could be and were modified to match the subgroup definitions established by the dlqi/cdlqi • data for each age group were evaluated as follows: – short-term (week 4) • asdd/asdd-c item 2 responder rate (≥4-point improvement from baseline) • median absolute change from baseline in gravimetrically-measured sweat production • hdss responder rate (≥2-grade improvement from baseline) • mean change from baseline in dermatology life quality index (dlqi) and children’s dlqi (cdlqi) – long-term (week 44/end of treatment [et]) • median absolute change from baseline in gravimetrically-measured sweat production • hdss responder rate (≥2-grade improvement from baseline) • mean change from baseline in dermatology life quality index (dlqi) and children’s dlqi (cdlqi) • in the evaluation of the double-blind data: – all efficacy analyses were conducted on the intent-to-treat (itt) population (all patients who were randomized and dispensed study drug) • the markov chain monte carlo method for multiple imputation was used for missing efficacy data • asdd/asdd-c item 2 responder rate was analyzed using the cochran-mantel-haenszel test; change from baseline in sweat production and change from baseline in dlqi were each analyzed using an analysis of covariance (ancova) model and there was no imputation for missing values; no imputation was made for missing dlqi and cdlqi data – safety analyses were conducted on the safety population (all randomized patients who received ≥1 confirmed dose of study drug); no imputation was made for missing safety data • for the long-term open-label extension study, safety and efficacy analyses were performed on the safety population (patients receiving ≥1 dose of gt and having ≥1 post-baseline assessment in arido) • statistical comparisons were not performed as the analysis was post hoc and not designed or powered to detect differences in the pediatric population results disposition, demographics, and baseline disease characteristics • in the pooled population of atmos-1 and atmos-2, 463 patients were randomized to gt and 234 to vehicle; 426 (92.0%) and 225 (96.2%) completed the trials, respectively (figure 2) • demographics and baseline disease characteristics were generally well matched among treatment arms and between the pediatric and older subgroups (table 1) – ages of the pediatric and older subgroup patients ranged from 9-16 and 17-76, respectively – although the older subgroup had greater gravimetrically-measured sweat production at baseline, the standard deviations were large across all treatment groups for this assessment • a total of 564/651 (86.6%) who completed atmos-1/atmos-2 entered arido, 226/564 (40.1%) completed week 44, and 550 comprised the analysis population figure 2. patient disposition gt n=25 vehicle n=19 n=24 (96.0%) n=564 (86.6%) n=305 (58.0%)n=27 (71.1%) n=210 (39.9%)n=16 (42.1%) n=19 (100.0%) gt n=438 vehicle n=215 n=402 (91.8%)n=206 (95.8%) 697 randomized ≥9 to ≤16 years, n=44 >16 years, n=653 ≥9 to ≤16 years, n=38 >16 years, n=526 completed atmos-1 & atmos-2 entered arido patients in arido at time of early study terminationa completed arido aper protocol, sponsor terminated study early when study objective of 100 patients receiving treatment for at least 12 months was achieved gt, topical glycopyrronium tosylate table 1. patient demographics and baseline disease characteristics (baseline of double-blind trials) ≥9 to ≤16 years >16 years vehicle n=19 gt n=25 vehicle n=215 gt n=438 demographics age (years) mean ± sd 14.1 ± 1.7 14.6 ± 1.4 35.1 ± 11.2 33.3 ± 10.5 median 14.0 15.0 33.0 32.0 range 9 – 16 11 – 16 17 – 76 17 65 sex, n (%) male 4 (21.1) 5 (20.0) 110 (51.2) 207 (47.3) female 15 (78.9) 20 (80.0) 105 (48.8) 231 (52.7) white, n (%) 17 (89.5) 18 (72.0) 179 (83.3) 356 (81.3) baseline disease characteristics sweat production (mg/5 min),a mean ± sd 151.7 ± 150.6 145.8 ± 133.4 178.4 ± 163.0 174.0 ± 219.5 asdd/asdd-c item 2 (sweating severity), mean ± sd 6.7 ± 1.7 7.5 ± 1.2 7.2 ± 1.6 7.3 ± 1.6 hdss, n (%) grade 3 14 (73.7) 15 (60.0) 141 (65.6) 262 (59.8) grade 4 5 (26.3) 10 (40.0) 73 (34.0) 176 (40.2) dlqi, mean ± sd nac nac 10.6 ± 5.9 11.9 ± 6.1 cdlqi,b mean ± sd 8.5 ± 5.6 9.9 ± 5.5 nac nac agravimetrically-measured average from the left and right axillae bn=24 for gt group ≥9 to ≤16 years of age cpatients ≥9 to ≤16 years of age were administered the cdlqi and patients >16 years of age were administered the dlqi intent-to-treat (itt) population asdd, axillary sweating daily diary; asdd-c, asdd-children; cdlqi, children’s dlqi; dlqi, dermatology life quality index; gt, topical glycopyrronium tosylate; hdss, hyperhidrosis disease severity scale; na, not applicable; sd, standard deviation short-term efficacy (week 4) • efficacy results (asdd item 2 responder rate, gravimetric sweat production, hdss responder rate, and dlqi/cdlqi) at week 4 were consistent among the pediatric and older subgroups, with similar improvements in sweating severity, sweat production, and quality of life observed at week 4, regardless of age – asdd/asdd-c item 2 responder rates (≥4-point improvement from baseline) were similar among gt-treated patients in the pediatric and older subgroups (59.9% versus 60.2%, respectively), and substantially greater for gtversus vehicle-treated patients regardless of age subgroup (figure 3) figure 3. asdd/asdd-c item 2 responder rate (≥4-point improvement) at week 4 vehicle n=19 13.0 gt n=25 59.9 vehicle n=215 28.8 gt n=438 60.2 ≥9 to ≤16 years >16 years 100 90 80 70 50 60 10 20 30 40 0 p ro po rt io n of p at ie nt s (% ) 0 pooled atmos-1/atmos-2 data; intent-to-treat (itt) population; p-values were not calculated for this post hoc analysis; multiple imputation (mcmc) was used to impute missing values; asdd/asdd-c was not assessed in arido; therefore, there are no data available for comparison of shortversus long-term efficacy asdd, axillary sweating daily diary; asdd-c, asdd-children; gt, topical glycopyrronium tosylate; mcmc, markov chain monte carlo – although gt-treated patients in the older subgroup had greater median absolute reduction from baseline in gravimetrically-measured sweat production compared with the pediatric subgroup (-80.6 vs -64.2, respectively), gttreated patients in both subgroups had greater median absolute change compared with vehicle-treated patients (table 2) – hdss responder rate at week 4 was similar among gt-treated pediatric and older subgroup patients (61.3% vs 58.7% of patients); both gt treatment groups had a markedly higher hdss responder rate compared with the vehicle treatment groups (table 2) – mean improvement from baseline at week 4 in cdlqi was consistent with that observed for dlqi in gt-treated patients in the pediatric and older subgroups (-8.1 vs -8.4); the vehicle response was greater in the older subgroup • mean improvements in cdlqi and dlqi scores were approximately 4-fold and 2-fold greater, respectively, for gt-treated patients compared with vehicle-treated patients in each subgroup, indicating a positive impact of gt treatment on health-related quality of life (table 2) table 2. gravimetric sweat production, hdss responder rate, and dlqi (week 4) ≥9 to ≤16 years >16 years vehicle n=19 gt n=25 vehicle n=215 gt n=438 median absolute change from baseline in sweat production,a mg/5 min, mean ± sd -53.7 ± 110.6 -64.2 ± 142.6 -62.0 ± 141.9 -80.6 ± 210.5 proportion of patients achieving hdss response (≥2-grade improvement from baseline), % 20.3 61.3 26.0 58.7 mean change from baseline in cdlqi/dlqi cdlqib (patients ≥9 to ≤16 years) -1.9 -8.1 --------dlqic (patients >16 years) ---------4.7 -8.4 agravimetrically-measured average from the left and right axillae; bn=23 for gt; cn=206 and n=405 for vehicle and gt, respectively pooled atmos-1/atmos-2 data; intent-to-treat (itt) population p-values were not calculated for this post hoc analysis; multiple imputation (mcmc) was used to impute missing values for sweat production and hdss responder rate cdlqi, children’s dlqi; dlqi, dermatology life quality index; gt, topical glycopyrronium tosylate; hdss, hyperhidrosis disease severity scale; mcmc, markov chain monte carlo; sd, standard deviation long-term efficacy (through week 44) • through week 44/et in arido (up to 48 weeks of gt from the start of the double-blind atmos-1/atmos-2 trials), improvements in efficacy measures, including sweat production, hdss responder rate, and dlqi/cdlqi, were maintained, with similar results between the pediatric and older subgroups (figure 4) – from baseline in atmos-1/atmos-2 to week 44/et in arido: • median sweat production decreased by -50.3 and -75.1 mg/5 minutes in the pediatric and older subgroups, respectively, reflecting a maintenance of sweat reduction benefit (median decreases were 61.3 and 58.7 mg/5 minutes in gt-treated patients after 4 weeks of gt treatment in the double-blind trials) • the proportion of hdss responders was consistent over the study course and similar to that observed after 4 weeks of gt treatment in the double-blind trials (59.9% and 60.2%, pediatric and older subgroups, respectively) • mean dlqi and cdlqi scores improved by 8.7 ± 6.2 and 6.2 ± 4.9, which were maintained from a mean decrease of 8.4 ± 6.0 and 8.1 ± 5.4, respectively, in gt-treated patients after 4 weeks of treatment in atmos 1/atmos-2 figure 4. arido outcomes at week 44/end of treatment ≥9 to ≤16 years n=30 -50.3 >16 years n=400 -75.1 ≥9 to ≤16 years n=26 -6.2 >16 years n=406 -8.7 ≥9 to ≤16 years n=30 56.7 >16 years n=407 63.6 sweat productiona hdss responder rate cdlq/dlqi 0 -80 -60 -40 -20 -100 m ed ia n a bs ol ut e c ha ng e fr om b as el in eb (m g/ 5 m in ) 0 -8 -6 -4 -2 -10 100 20 40 60 80 0p ro po rt io n of p at ie nt s (% ) m ea n c ha ng e fr om b as el in e agravimetrically-measured average from the left and right axillae; bbaseline in atmos-1/atmos-2 for vehicle-treated and gt-treated patients who continued into arido and received gt-treatment thereafter pooled atmos-1/atmos-2 data; intent-to-treat (itt) population p-values were not calculated for this post hoc analysis; multiple imputation (mcmc) was used to impute missing values for sweat production and hdss responder rate cdlqi, children’s dlqi; dlqi, dermatology life quality index; et, end of treatment/early termination; gt, topical glycopyrronium tosylate; hdss, hyperhidrosis disease severity scale; mcmc, markov chain monte carlo; sd, standard deviation safety • overall, gt was well tolerated across short and long-term treatment, and most adverse events were mild to moderate in severity, and infrequently led to discontinuation, regardless of age (table 3) – of two serious teaes reported in the double-blind trials, both occurred in the gt arm of the older subgroup and only one lead to discontinuation (moderate unilateral mydriasis; related to treatment) table 3. safety overview (double-blind trials and open-label extension by age) na (%) double-blind trials open-label extension ≥9 to ≤16 years >16 years ≥9 to ≤16 years >16 years vehicle n=19 gt n=25 vehicle n=213 gt n=434 gt n=22 gt n=512 any teae 2 (10.5) 11 (44.0) 73 (34.3) 246 (56.7) 22 (57.9) 307 (60.0) any serious teae 0 0 0 2 ( 0.5) 0 7 ( 1.4) deaths 0 0 0 0 0 0 discontinuation due to teae 0 1 ( 4.0) 1 ( 0.5) 17 ( 3.9) 1 ( 2.6) 42 ( 8.2) teae by intensity mild 2 (10.5) 6 (24.0) 51 (23.9) 164 (37.8) 14 (36.8) 134 (26.2) moderate 0 4 (16.0) 22 (10.3) 79 (18.2) 7 (18.4) 146 (28.5) severe 0 1 ( 4.0) 0 3 ( 0.7) 1 ( 2.6) 27 ( 5.3) anumbers in table represent the number of patients reporting ≥1 teae, not number of events pooled atmos-1/atmos-2 and arido safety population gt, topical glycopyrronium tosylate; teae, treatment-emergent adverse event • during both short and long-term treatment with gt, the majority of teaes reported in the gt group were related to anticholinergic activity – anticholinergic teaes were similar between subgroups and between atmos-1/atmos-2 and arido (table 4) • the most frequently reported anticholinergic teae in gt-treated patients during both the double-blind trials and the open-label extension was dry mouth • unlike mydriasis events in the older subgroup, which were largely unilateral (22 of 27 events), the majority of events in the pediatric subgroup were bilateral (3 of 4 events). although difficult to determine given the small number of events, this may be attributed to pediatric patients being more likely to touch both eyes after gt application or possibly anticholinergic effects resulting from systemic exposure, which are minimized but not eliminated completely by topical gt application table 4. anticholinergic-related teaes during the double-blind trials and open-label extension nb (%) double-blind trials open-label extension ≥9 to ≤16 years >16 years ≥9 to ≤16 years >16 years vehicle n=19 gt n=25 vehicle n=213 gt n=434 gt n=38 gt n=512 mydriasis 0 4 (16.0)c 0 27 ( 6.2)d 3 ( 7.9)e 26 ( 5.1)f vision blurred 0 3 (12.0) 0 13 ( 3.0) 4 (10.5) 33 ( 6.4) dry eye 0 1 ( 4.0) 1 (0.5) 10 ( 2.3) 0 16 ( 3.1) dry mouth 0 6 (24.0) 13 (6.1) 105 (24.2) 6 (15.8) 87 (17.0) urinary hesitation 0 0 0 16 ( 3.7) 1 ( 2.6) 22 ( 4.3) urinary retention 0 1 ( 4.0) 0 6 ( 1.4) 0 0 nasal dryness 0 1 ( 4.0) 1 (0.5) 11 ( 2.5) 1 ( 2.6) 19 ( 3.7) constipation 0 0 0 9 ( 2.1) 1 ( 2.6) 7 ( 1.4) ain either treatment arm in either age subgroup in the pooled population bnumbers in table represent the number of patients reporting ≥1 teae, not number of events c4 patients reported 1 unilateral event and 3 bilateral events d27 patients reported 23 unilateral events and 5 bilateral events e3 patients reported 3 unilateral events f26 patients reported 28 unilateral events and 6 bilateral events pooled atmos-1/atmos-2 data; safety population gt, topical glycopyrronium tosylate; teae, treatment-emergent adverse event conclusions • in this post hoc analysis of two large, 4-week, phase 3 trials and their 44-week open-label extension, pediatric patients (≥9 to <16 years) treated once daily with gt demonstrated – improved disease severity, reduced sweat production, and improved quality of life relative to vehicle at week 4, with improvements maintained for an additional 44 weeks of open label gt – similar efficacy findings to older patients – teae profile similar to older patients with teaes that were typically mild, and infrequently led to discontinuation • the availability of topical, once-daily gt provides a noninvasive, effective treatment option for both adults and pediatric patients with primary axillary hyperhidrosis references 1. doolittle et al. arch dermatol res. 2016;308(10):743-749. 2. hebert et al. oral (late-breaker) presented at 75th annual meeting of the american academy of dermatology; 2017; orlando, fl. 3. strutton et al. j am acad dermatol. 2004;51(2):241-248. 4. gelbard et al. pediatr dermatol. 2008;25(6):591-598. 5. qbrexzatm (glycopyrronium) cloth [prescribing information]. dermira, inc., menlo park, ca. in:2018. 6. glaser et al. j am acad dermatol. 2018 (in preparation). 7. hebert et al. oral presented at 27th international congress of the european academy of dermatology and venereology; september 12-16, 2018, 2018; paris, france. 8. glaser et al. poster presented at 76th annual meeting of the american academy of dermatology; february 16-20, 2018; san diego, ca. 9. glaser et al. poster presented at 13th annual maui derm for dermatologists; 2017; maui, hi. acknowledgements these studies were funded by dermira, inc. medical writing support was provided by prescott medical communications group (chicago, il) with financial support from dermira, inc. disclosures aah: consultant for dermira, inc.; employee of the university of texas medical school, houston, which received compensation from dermira, inc. for study participation. dag: consultant and investigator for dermira, inc. lg: consultant and investigator for dermira, inc.; investigator for brickell biotech, inc. wpw: consultant and investigator for dermira, inc. df: consultant for dermira, inc.; investigator for jordan valley dermatology and research center. jd, rg: employee of dermira, inc. dmp: consultant and investigator for dermira, inc. skin july 2021 1237 proof returned skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 347 in-depth review molecular pathogenesis and complications associated with keratosis follicularis: a clinical review hira ghani, ba1, stefani cubelli, do2, raphia k. rahman, ba, mbs3, alexandra chervonsky, ba, ma1 1new york institute of technology college of osteopathic medicine, old westbury, ny 2st. john’s episcopal hospital, far rockaway, ny 3rowan school of osteopathic medicine, rowan, nj in 1889, dr. james c. white, a professor of dermatology at harvard university published the first case report of a patient with keratosis follicularis, whose skin appeared to be occupied with a variety of lesions, some of which were the “size of a pinhead, smooth and firm”, while others were slightly larger, but similar in appearance. the same year, independently from dr. white in paris, dr. darier published another case report of a patient with a similar presentation. keratosis follicularis or darier's disease (dd), a rare autosomal dominant disorder, is characterized clinically by the appearance of multiple, pruritic, discrete, scaly papules affecting seborrheic areas coupled with palmar pits, nail changes and mucosal involvement.1 these hyperkeratotic papules can be present on the middle of the chest, upper shoulders, neck and face.2 the papules coalesce into plaques which can appear papillomatous and may become hypertrophic, malodorous, painful and prone to secondary infections.2, 3 the disorder is a relatively common genodermatosis and affects approximately 1 in 36,000 individuals. it is characterized by late age of onset and typically presents in the first or second decade. histologically, dd is characterized by the presence of dyskeratotic cells, also known as corps rounds, which are small round keratinocytes with basophilic nuclei, and acantholysis–loss of intercellular connection between keratinocytes.3 topical tazarotene, topical isotretinoin, topical adapalene and oral retinoids have been reported to be effective for the treatment of mild-to-moderate keratosis abstract keratosis follicularis or darier's disease (dd) is a rare autosomal dominant disorder characterized by the appearance of multiple scaly papules affecting seborrheic areas. it is a multisystem disorder that occurs in the first or second decade of life, and extends beyond cutaneous involvement. it has been reported to be associated with various basal cell carcinoma (bcc) and other skin cancers, nail changes, ocular/mucosal manifestations and neuropsychiatric disorders. additionally, individuals with dd have a greater risk of being diagnosed with type 1 diabetes mellitus as well as disease-specific risk of heart failure. the goal of this review is to explore the molecular pathogenesis of keratosis follicularis, and to investigate the extent and severity of various complications associated with this condition. furthermore, dermatologic practice recommendations will be reviewed for the management of dd. introduction skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 348 follicularis.4-6 surgical options for severe or refractory disease include dermabrasion, carbon dioxide laser, and neodymium-doped yttrium aluminum garnet (yag) laser. 7 more recently, the role of naltrexone has also been explored in treating dd. while low-dose naltrexone has been quite successful in treating hailey-hailey disease, a genodermatosis similar to dd with a genetic mutation coding for a loss of function of a ca2+ -atpase pump (hspca1-pump), it has shown worsening of symptoms after initial treatment when used for severe dd.8 however, low-dose naltrexone has been an effective and viable treatment option for the treatment of mild-to-moderate spectrum of dd.8 further, dd may be exacerbated by ultraviolet light exposure, particularly ultraviolet b, as well as by heat, humidity, and friction. additionally, the use of topical sunscreens and ascorbic acid have been shown to be effective in the prevention of disease flares.9 dd has been reported in association with non-melanoma skin cancers (nmsc), including various basal cell carcinomas (bcc), as well as neuropsychiatric disorders such as bipolar disorder.10, 11 moreover, rare cases involving nail changes and ocular manifestations have also been observed in connection with dd. it was also found that individuals with dd have an elevated risk of being diagnosed with type 1 diabetes, and show an increased risk of heart failure which should be taken into account in patient management. 12 thus, the purpose of this literature review is to explore the molecular pathogenesis of dd, investigate the various complications associated with dd, and to elucidate the degree to which these complications are observed in patients suffering from dd. molecular pathogenesis of keratosis follicularis dd is caused by genetic defects in atp2a2 encoding the sarcoplasmic/endoplasmic reticulum ca(2+)-atpase isoform 2 (serca2). 13 serca2 is a calcium pump of the endoplasmic reticulum (er) transporting ca(2+) from the cytosol to the lumen of er. atp2a2 mutations lead to loss of ca(2+) transport by serca2 resulting in decreased er ca(2+) concentration in darier keratinocytes. 13 this eventually results in loss of cell-to-cell adhesion and abnormal keratinization. 13 the alternative splicing of atp2a2 gene gives rise to two isoforms of serca2 pump: serca2a, which is predominantly found in skeletal and cardiac muscles, and serca2b, which is found in all cell types but abundantly in smooth muscle cells. 14, 15 serca2b is different from serca2a by the presence of the “2b tail”. 16 it has been suggested that wildtype serca2b in keratinocytes exhibits high calcium affinity with the low transport rate, while mutations in serca2b lead to increased cytosolic calcium with the decreased peak calcium, and thus impairs the dynamic of calcium signaling. 16 a high concentration of calcium inside of the er is needed for the posttranslational processing of proteins that are destined to reach the plasma membrane. depletion of calcium concentration in er is associated with the accumulation of misfolded proteins in er, which leads to initiation of stress response. 17 it has been shown that constant er stress response leads to decreased adherens junction formations between the cells. 17 it has been also observed that loss of serca2b leads to formation of defective adherens junctions and desmosomes, which results skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 349 results in diminished intercellular adhesion. 17 in other words, mutations in atp2a2 that cause defective serca2b lead to low calcium concentration inside of er, and thus impair proper processing of proteins that are responsible for cell-to-cell adhesion. dd and basal cell carcinoma according to a variety of literature, an association has been found between dd and basal cell carcinoma (bcc). while no molecular link between dd and bcc has been established, the imbalance of cellular survival and apoptosis due to the dd mutation or other genodermatoses may contribute to the presence of bcc in individuals with dd. darier's disease is caused by a loss-of-function mutation in the atp2a2 that leads to a disruption of ca2+homeostasis within the keratinocytes. a decreased serca activity leads to an upregulation of the transient receptor potential canonical 1 ca channel that increases cell proliferation and resistance to apoptosis. 18 additionally, it has been demonstrated that patients with dd have reduced expression of the antiapoptotic proteins bcl-2 and bcl-xl, which may activate apoptosis and lead to increased cell turnover. 19 although quite rare, cases of squamous cell carcinoma (scc) have also been seen in patients with dd. robertson and sauder report that at least 7 cases of scc have been observed in association with dd since 1981. 20 however, no association was determined between dd and melanoma, merkel cell cancer or any other kind of skin cancer. more investigation needs to be done to establish a relationship between dd and cutaneous malignancies that are not nmsc. 20 moreover, alteration of atp2a2 gene has been reported in the development of various other human carcinomas including colon and lung cancers. 21 dd and cutaneous, ocular & mucosal manifestations nail involvement in individuals suffering from dd is not uncommon, and is frequently characterized by red or white longitudinal bands of varying width ending in a pathognomonic notch at the free margin of the nail, and subungual hyperkeratosis. usually, the nails are found to be very fragile and brittle. mucosal membrane involvement may occur as white papules on the buccal mucosae, palate, and gingiva with a cobblestone appearance. 22 being a predominantly dermatological disease, ocular manifestations are rare in keratosis follicularis. they can present as punctuate corneal epithelial defects (photophobia), asymptomatic opacities in periphery of cornea, bilateral corneal subepithelial infiltrations, corneal ulcerations, or conjunctival keratosis.23-25 patients with darier's are also prone to recurrent herpes keratitis and episcleritis. 26 there have been rare reports of other abnormalities including cataracts, basal cell carcinoma, retinal detachment, and in some patients, typical retinitis pigmentosa and even horn-like growths along the lid margin. 27-29 dd and neuropsychiatric conditions it has been observed that dd is associated with multiple neuropsychiatric conditions, such as major depression, bipolar disorder, schizophrenia, and suicidal ideations. 30 it was found that individuals with dd have a higher chance of being diagnosed with bipolar disorder and schizophrenia (4.3 and 2.3 fold higher, respectively). 11 it is thought that the genetic variability within the atp2a2 gene which causes dd confers susceptibility for bipolar disorder in some patients suffering from dd. 11 another study, that analyzed the results of standardized neuropsychiatric tests of one hundred individuals diagnosed with dd, suggests that neuropsychiatric symptoms of dd are rather the result of skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 350 atp2a2 gene mutation, than the psychological response of the individuals to the cutaneous manifestation of dd. 30 even though multiple mutations of atpa2a2 are linked to dd, only specific locations of atp2a2 mutations are associated with neuropsychiatric symptoms. 31 this relationship can be explained by the pleomorphic effect of atpa2a loss of function mutations. 32 dd and diabetes the relationship between dd and diabetes has also been observed. in a study conducted by cederlöf et al, it was found that individuals with dd had a higher risk of being diagnosed with type 1 diabetes (risk ratio, 1.74; 95% confidence interval, 1.13-2.69) than those having type 2 diabetes (risk ratio, 0.88; 95% confidence interval, 0.37-1.36). 12 given that most individuals with dd have mutations in atp2a2, it is possible that the increased risk of type 1 diabetes is associated with atp2a2 mutations and serca2 dysfunction. 12 moreover, in the recent cross-sectional clinical study of metabolic phenotype of dd, it has been found that dd patients have lower fasting glucose level and higher c-peptide and homa2-%beta compared to their matched control group. 33 this indicates that dd patients have a higher secretory capacity of islet cells and a higher basal insulin level. the authors emphasize that increased basal insulin is associated with worse control of glucose, and with time, may lead to type 2 diabetes. 33 the relationship between glucose metabolism and dd may be due to the fact that among different serca isoforms, serca2b is most abundantly expressed in pancreatic beta-cells. 14 it has been shown that the loss of serca2b due to mutations in atp2a2, as seen in individuals with dd, leads to secretory dysfunction, and defect in proliferation and survival of betacells. 34 additionally, inhibition of serca2b in beta-cells leads to initiation of the stress response by er that induces apoptosis. 35 dd and heart disease furthermore, it has been hypothesized that dd may be associated with heart diseases. this observation also strengthens the clinical evidence of the important role of serca2 in heart failure pathophysiology. 36 for example, even though patients with dd present with a normal clinical heart phenotype, they have a 59% higher chance of being diagnosed with heart failure compared to those without dd. 36 interestingly, the loss of the atpa2a allele by itself does not affect cardiac performance, however, the development of heart conditions may be worsened in patients with atpa2a mutation. 37 it can be concluded that dd is a multisystem rare autosomal dominant disorder that occurs typically in the first or second decade of life, and goes beyond involving the skin. while neuropsychiatric manifestations, diabetes mellitus type 1 and heart diseases are more commonly observed, rare instances of mucosal, nail and ocular changes have also been reported to occur in association with dd. since uv light exposure exacerbates the condition, we recommend individuals with dd to avoid direct sunlight and apply sunscreen when going out. furthermore, mild to moderate dd management includes the use of oral and topical retinoid as well as naltrexone. dermabrasion and carbon dioxide or yag laser are reserved for severe and refractory cases. it is crucial for dermatologists to anticipate and discern the extracutaneous manifestations associated with dd in order to be able to provide a timely and appropriate referral to other specialists, conclusion skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 351 including psychiatrists, endocrinologists and cardiologists, for further management. conflict of interest disclosures: none funding: none corresponding author: hira ghani, ba 259 palsa avenue elmwood park, nj 07407 phone: 201-925-5165 e-mail: hghani01@nyit.edu references: 1. mahboob a, yaqub f, shahzad z, et al. classical presentation of darier's disease: a rare disorder of keratinisation. j ayub med coll abbottabad. jul-sep 2010;22(3):230-3. 2. schmieder sj, rosario-collazo ja. keratosis follicularis. statpearls. statpearls publishing copyright © 2020, statpearls publishing llc.; 2020. 3. suryawanshi h, dhobley a, sharma a, kumar p. darier disease: a rare genodermatosis. j oral maxillofac pathol. may-aug 2017;21(2):321. doi:10.4103/jomfp.jomfp_170_16 4. oster-schmidt c. the treatment of darier's disease with topical tazarotene. br j dermatol. sep 1999;141(3):603-4. doi:10.1046/j.13652133.1999.03089.x 5. mckenna ke, walsh my, burrows d. treatment of unilateral darier's disease with topical isotretinoin. clin exp dermatol. sep 1999;24(5):425-7. doi:10.1046/j.13652230.1999.00519.x 6. english jc, 3rd, browne j, halbach dp. effective treatment of localized darier's disease with adapalene 0.1% gel. cutis. apr 1999;63(4):22730. 7. beier c, kaufmann r. efficacy of erbium:yag laser ablation in darier disease and hailey-hailey disease. arch dermatol. apr 1999;135(4):423-7. doi:10.1001/archderm.135.4.423 8. boehmer d, eyerich k, darsow u, biedermann t, zink a. variable response to low-dose naltrexone in patients with darier disease: a case series. j eur acad dermatol venereol. 2019;33(5):950953. doi:10.1111/jdv.15457 9. heo ep, park sh, yoon tj, kim th. induction of darier's disease by repeated irradiation by ultraviolet b; protection by sunscreen and topical ascorbic acid. j dermatol. jul 2002;29(7):455-8. doi:10.1111/j.1346-8138.2002.tb00306.x 10. soroush v, gurevitch aw. darier's disease associated with multiple café-au-lait macules. cutis. 1997/04// 1997;59(4):193-195. 11. cederlöf m, bergen se, långström n, et al. the association between darier disease, bipolar disorder, and schizophrenia revisited: a population-based family study. bipolar disord. may 2015;17(3):340-4. doi:10.1111/bdi.12257 12. cederlöf m, curman p, ahanian t, et al. darier disease is associated with type 1 diabetes: findings from a population-based cohort study. j am acad dermatol. dec 2019;81(6):1425-1426. doi:10.1016/j.jaad.2019.05.087 13. savignac m, edir a, simon m, hovnanian a. darier disease : a disease model of impaired calcium homeostasis in the skin. biochim biophys acta. may 2011;1813(5):1111-7. doi:10.1016/j.bbamcr.2010.12.006 14. chemaly er, troncone l, lebeche d. serca control of cell death and survival. cell calcium. jan 2018;69:46-61. doi:10.1016/j.ceca.2017.07.001 15. verboomen h, wuytack f, de smedt h, himpens b, casteels r. functional difference between serca2a and serca2b ca2+ pumps and their modulation by phospholamban. biochem j. sep 1 1992;286 ( pt 2)(pt 2):591-5. doi:10.1042/bj2860591 16. robia sl, young hs. skin cells prefer a slower calcium pump. j biol chem. mar 16 2018;293(11):3890-3891. doi:10.1074/jbc.h118.002088 17. savignac m, simon m, edir a, guibbal l, hovnanian a. serca2 dysfunction in darier disease causes endoplasmic reticulum stress and impaired cell-to-cell adhesion strength: rescue by miglustat. j invest dermatol. jul 2014;134(7):1961-1970. doi:10.1038/jid.2014.8 18. pani b, cornatzer e, cornatzer w, et al. upregulation of transient receptor potential canonical 1 (trpc1) following sarco(endo)plasmic reticulum ca2+ atpase 2 gene silencing promotes cell survival: a potential role for trpc1 in darier's disease. mol biol cell. oct 2006;17(10):4446-58. doi:10.1091/mbc.e0603-0251 19. pasmatzi e, badavanis g, monastirli a, tsambaos d. reduced expression of the antiapoptotic proteins of bcl-2 gene family in the lesional epidermis of patients with darier's disease. journal of cutaneous pathology. 04/01 2007;34:234-8. doi:10.1111/j.16000560.2006.00600.x 20. robertson l, sauder mb. basal cell carcinoma in type 2 segmental darier's disease. j skin skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 352 cancer. 2012;2012:839561. doi:10.1155/2012/839561 21. korosec b, glavac d, rott t, ravnik-glavac m. alterations in the atp2a2 gene in correlation with colon and lung cancer. cancer genet cytogenet. dec 2006;171(2):105-11. doi:10.1016/j.cancergencyto.2006.06.016 22. kosann mk. keratosis follicularis. dermatol online j. oct 2003;9(4):35. 23. blackman hj, rodrigues mm, peck gl. corneal epithelial lesions in keratosis follicularis (darier's disease). ophthalmology. sep 1980;87(9):93143. doi:10.1016/s0161-6420(80)35142-7 24. mohamed kn. darier's disease and corneal opacity. dermatologica. 1991;182(3):205. doi:10.1159/000247787 25. roy fh. ocular syndromes and systemic diseases. 4th ed. medrounds publications, inc.; 2008:396. 26. radia m, gilhooley mj, panos c, claoué c. recurrent presumed herpes simplex keratitis and episcleritis in keratosis follicularis (darier's disease). bmj case rep. jul 16 2015;2015doi:10.1136/bcr-2015-210772 27. russell dj, dutton jj, fowler am. darier disease mimicking basal cell carcinoma of the eyelid. ophthalmic plastic & reconstructive surgery. 2009;25(2):144-146. doi:10.1097/iop.0b013e31819aadad 28. itin p, büchner sa, gloor b. darier's disease and retinitis pigmentosa; is there a pathogenetic relationship? br j dermatol. sep 1988;119(3):397-402. doi:10.1111/j.13652133.1988.tb03235.x 29. wright jc. darier's disease. am j ophthalmol. jan 1963;55:134-6. doi:10.1016/00029394(63)91659-3 30. gordon-smith k, jones la, burge sm, munro cs, tavadia s, craddock n. the neuropsychiatric phenotype in darier disease. br j dermatol. sep 2010;163(3):515-22. doi:10.1111/j.1365-2133.2010.09834.x 31. karagas ne, venkatachalam k. roles for the endoplasmic reticulum in regulation of neuronal calcium homeostasis. cells. oct 10 2019;8(10)doi:10.3390/cells8101232 32. nakamura t, kazuno aa, nakajima k, kusumi i, tsuboi t, kato t. loss of function mutations in atp2a2 and psychoses: a case report and literature survey. psychiatry clin neurosci. aug 2016;70(8):342-50. doi:10.1111/pcn.12395 33. ahanian t, curman p, leong ius, et al. metabolic phenotype in darier disease: a crosssectional clinical study. diabetol metab syndr. 2020;12:12. doi:10.1186/s13098-020-0520-0 34. tong x, kono t, anderson-baucum ek, et al. serca2 deficiency impairs pancreatic β-cell function in response to diet-induced obesity. diabetes. oct 2016;65(10):3039-52. doi:10.2337/db16-0084 35. cardozo ak, ortis f, storling j, et al. cytokines downregulate the sarcoendoplasmic reticulum pump ca2+ atpase 2b and deplete endoplasmic reticulum ca2+, leading to induction of endoplasmic reticulum stress in pancreatic betacells. diabetes. feb 2005;54(2):452-61. doi:10.2337/diabetes.54.2.452 36. bachar-wikstrom e, curman p, ahanian t, et al. darier disease is associated with heart failure: a cross-sectional case-control and population based study. sci rep. apr 2020;10(1):6886. doi:10.1038/s41598-020-63832-9 37. prasad v, lorenz jn, lasko vm, et al. serca2 haploinsufficiency in a mouse model of darier disease causes a selective predisposition to heart failure. biomed res int. 2015;2015:251598. doi:10.1155/2015/251598 skin december 2018 volume 2 supplemental issue copyright 2018 the national society for cutaneous medicine 103 rising derm stars topical cantharidin revisited: a phase 2 study investigating a commerciallyviable formulation of cantharidin (vp-102) for the treatment of molluscum contagiosum anthony k guzman md1, jessica l garelik do1, steven r cohen, md, mph1 1department of internal medicine, division of dermatology, albert einstein college of medicine, bronx, ny. background: molluscum contagiosum (mc) is a common cutaneous infection caused by a dna poxvirus, predominantly affecting children. there is a paucity of high quality evidence on which to make clinical decisions in treating mc. (1) cantharidin, a topical vesicant historically derived from a blister beetle, is a commonly-used treatment for this condition. however, despite the prevalence of its use, cantharidin is not fda-approved, is not standardized in formulation or treatment regimen and is not always manufactured in accordance with good manufacturing practices (gmp), leading to a lack of commercial availability. (2,3) objective: to determine the efficacy and safety of vp-102, a novel, standardized, commercially-viable cantharidin formulation produced under gmp for the treatment of mc. methods: we conducted a 12-week, openlabel pilot trial at a single outpatient dermatology clinic. subjects 2-17 years (n = 30) with a clinical diagnosis of mc and < 50 lesions were included. subjects were treated with a single-use vial containing a standardized 0.7% w/v cantharidin solution, produced under gmp (vp-102), applied with the wooden end of a cotton swab approximately every 21 days, for up to 4 treatments or until complete lesion clearance. subjects were instructed to wash treatment off all lesions at either 6 hours (cohort 1: 14/30, 46.7%) or 24 hours (cohort 2: 16/30, 53.3%), or earlier if significant blistering occurred. lesion counts and adverse events (aes), including local skin reactions, were documented at each visit. quality of life was also measured using the children’s dermatology quality of life index (cdlqi) at baseline and at the end of study (eos). the primary endpoint was the percentage of subjects achieving total clearance by eos on day 84. results: the mean patient age was 5.8 (range= 2-12 yrs). a total of 26 subjects (86.7%) experienced at least one expected local skin reaction such as blistering or erythema. no serious or unexpected treatment-related aes were encountered. a total of 25 subjects pooled from both cohorts completed the study. eleven subjects (44.0%) achieved total lesion clearance by eos. the mean ± sd lesion count was significantly reduced from 23.0 ± 15.6 at baseline to 6.8 ± skin december 2018 volume 2 supplemental issue copyright 2018 the national society for cutaneous medicine 104 11.7 at eos (p < 0.0001). the mean cdlqi score was markedly improved from 3.9 ± 5.6 at baseline to 0.38 ± 1.3 at eos (p = 0.01). conclusions: vp-102 was well-tolerated with either a 6 or 24-hour exposure and was associated with a significantly reduced lesion count, improved quality of life and complete clearance of mc lesions in nearly half of the patients. figure 1: lesion clearance after vp-102. references: references: 1. van der wouden jc, van der sande r, kruithof ej, sollie a, van suijlekom-smit lw, koning s. interventions for cutaneous molluscum contagiosum. the cochrane database of systematic reviews 2017;5:cd004767. 2. coloe j, morrell ds. cantharidin use among pediatric dermatologists in the treatment of molluscum contagiosum. pediatric dermatology 2009;26:405-408. 3. pompei dt, rezzadeh ks, viola kv, lee dh, schairer do, chismar la, et al. cantharidin therapy: practice patterns and attitudes of health care providers. journal of the american academy of dermatology 2013;68:1045-1046 skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 405 research letter the need for objective and remote tracking of chronic skin diseases olga k. afanasiev, md, phd,1 mika tabata, ba,2 justin m. ko, md, mba1 1stanford health care, department of dermatology, redwood city, ca 2stanford school of medicine, stanford, ca chronic skin diseases constitute a large proportion of dermatology visits and have a substantial economic burden on our healthcare system.1 while neoplasms can be tracked via measurements or photographs, chronic inflammatory skin diseases can have a prolonged and dynamic course that fluctuates in presentation, severity, and abstract importance: managing chronic skin disease is often frustrating for both providers and patients, sometimes resulting in delayed diagnosis, inadequate therapy, and inconsistent care. objective: this study performs stakeholder analyses to identify unmet clinical needs in chronic skin disease management. methods: survey of 33 providers and 25 patients at stanford health care dermatology department. results: when evaluating a chronic skin conditions (such as psoriasis), 79% of dermatologists rely solely on subjective documentation (gestalt, body surface area, descriptive exam). objective documentation (photographs or scoring assessment tools) is used by 21% of providers upon initial assessment and by 7% of providers to assess change in disease between office visits. while 83% of providers are comfortable assessing change in disease severity based on prior document by oneself, only 31% are comfortable assessing change based on prior documentation by another provider (p <0.001). dermatologists expressed the need for better documentation modality in clinic (94%), and in between office visits by patients (91%). while 90% of patients reported it is moderately to extremely important to track their disease, only 16% of patients consistently do. most patients preferred to monitor their disease at home (92%) using cameras (80%) or by smartphone (59%). patients were willing to spend 5-30 minutes weekly to monthly to document their disease. conclusions and relevance: this study identifies that dermatologists and patients need a solution that objectively and remotely monitors chronic skin diseases to guide treatments, empower patients, and provide more cohesive care in a complex healthcare system. introduction skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 406 distribution. during significant wait times for new dermatology referrals,2 patients are frequently evaluated by multiple providers and have significant change in their disease. unfortunately, subjective, fragmented documentation and imperfect memories may result in delayed diagnoses, inadequate control of disease burden, and inconsistent care. this study 1) identifies unmet clinical needs in management of chronic skin diseases, and 2) specifies characteristics of any potential solutions based on the relevant stakeholder analyses. institutional review board approval was received. patients with chronic dermatologic diseases (n=25, mean age 48.5 +/17.9 years) and two overlapping cohorts of 29 and 33 dermatologists were anonymously surveyed at the stanford health care dermatology clinic (july 2018 to december 2018). patients surveyed had psoriasis (9), atypical nevi or skin cancer history (7), lichen sclerosis (2), atopic dermatitis (1), tinea pedis (1), cysts (1), mycosis fungoides (1), acne (1), multiple conditions (1) and preferred not to say (1). statistical analyses were performed using 2-tailed fisher's exact test in excel. survey questionnaires are available from the corresponding author. dermatologists use subjective measures to document and assess for change in chronic skin diseases. upon initial evaluation of patients with psoriasis, 79% (23/29) providers document their exam and assessment using subjective measures (such as gestalt, body surface area, and descriptive exam) (figure 1). 21% (6/29) of providers supplement their subjective assessment with objective documentation (such as photographs or scoring assessment tools) (figure 1). when monitoring for change in disease activity between office visits, dermatologist also rely on patient perception of disease progression. for assessment of disease severity between office visits, 91% (27/29) rely solely on subjective measures and 7% (2/29) of providers use additional objective measures (figure 1). figure 1. documentation of psoriasis by dermatologists (n=29). yellow = subjective measures. blue = objective measures. bsa = body surface area. score = clinical assessment tools such as pasi (psoriasis area and severity index). methods results skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 407 clinical handoffs decrease the ability to assess for change in disease severity. when dermatologists were asked if they were comfortable assessing change in disease severity based on their own prior documentation, 83% (24/29) agreed or strongly agreed. if, however, prior documentation was by another provider, only 31% (9/29) agreed or strongly agreed that they were comfortable assessing change in disease (p<0.001, figure 2). figure 2. dermatologists’ (n=29) assessment of change in disease severity between visits. dermatologists reported they needed better documentation of chronic skin diseases in the office (94%) and at home (91%). they were willing to spend less than 1 minute (mean = 30 seconds) on capturing or interpreting captured data. patients want to track their skin disease in between office visits. a majority of patients (91%) reported that it is “moderately” (23%), “highly” (23%) or “extremely” (45%) important to have a way to “track/document disease between office visits”. most patients track their disease between office visits (68%), however only 16% of patients do it consistently (figure 3). of those who track their disease, most rely on observation and memory (41%), some take photographs (29%) or notes (18%). patients who do not track their disease at home attribute it to “no flares to document”, “inadequate capture modality”, “forgetfulness”, “unawareness.” patients are willing to spend time at home to document disease to improve outcomes. in terms of technology competence, most patients in our cohort considered themselves to be “average” (50%) to “above average” (36%), with only 5% “below average” and 9% “expert” level. patients were willing to spend an average of 16.5 minutes (range: 5-30 minutes) to document their disease weekly (40%), monthly (28%) or quarterly (20%). the documentation modality of choice was visual (photographs) (67%), followed by visual and written (13%) or written only (13%). preferred tools were smartphone (45%), computer (23%) or both (14%). patient preferred to document their disease at home (92%) rather than in an office or walk-in facility (8%). 50% of patients predicted that increased physician awareness of disease severity would result in better disease control. patients experiencing flares were more likely to respond that increased access to a doctor would result in better disease control (or=11.67 [0.92, 147.57], p=0.057). figure 3. patient responses (n=25) regarding their skin disease tracking practices between office visits. skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 408 this study identifies that 1) most dermatologists rely on subjective measures to document chronic diseases, 2) dermatologists lack confidence in assessing disease change if patient was previously seen by another provider and 3) dermatologists and patients need a way to objectively document and track changes in chronic skin diseases in the office and at home. currently, the text-based physical exam is the gold standard for documenting chronic skin diseases. however, seemingly objective measures such as approximate body surface area and descriptive exam have inherent intraand inter-provider variability.3,4 numerous assessment scales (53 for psoriasis,5 11 for atopic dermatitis6) lack consensus for interpretation and validity. standard total body photography has gained little traction for documentation of rashes likely because it is inconsistent, overly cumbersome and labor-intensive for clinical workflows. this lack of objective assessment tools is problematic, especially during patient “handoffs”, which can lead to diagnostic delay, inconsistent management and overall suboptimal care. patients are often frustrated by the inability to consistently and accurately capture disease severity and emotional burden at home. studies have demonstrated the necessity to capture patient-reported outcomes (symptoms, emotional and functional impact).7.8 prior studies indicate that patients are willing to pay us$10 for mobile health app services.9 we show that patients are committed to regularly documenting their skin disease at home. while there are many emerging tools and mobile applications for monitoring individual neoplasms,10 dermatologists and patients lack an objective and efficient tool to robustly document and longitudinally monitor changes in chronic and inflammatory skin conditions. existing smartphone applications either track pre-existing and patient-defined lesions on specific anatomic body parts or have only a rough full body overlay schematic of disease. while major electronic health records systems (such as epic) are capable of accepting patient generated health data between visits (via mychart portal), many offices do not provide that service, and those that do, find the between office media data difficult to integrate into the current workflow.11 lastly, 3d full body multi-camera imaging systems (such as canfield) are expensive and with limited access to most patients. as our healthcare continues to move towards value-based payment models, we will need to demonstrate the impact of our care and treatments. individualized disease tracking tools may facilitate improved outcomes at a decreased cost to the healthcare system. further, the centers for medicare & medicaid services, has introduced a set of reimbursement codes around remote patient monitoring and telehealth services.12 limitations of this study include single institution analyses among a small cohort of patients. there exists a need for skin monitoring solution that is robust, universal, cheap, and easily integrated into provider visits and home use to optimize treatments, empower patients, and promote personalized, engaging, and active approach to care in a complex medical system. discussion skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 409 irb/consent: an appropriate institutional review board approved the project, and informed consent was appropriately obtained. conflict of interest disclosures: none funding: none corresponding author: olga afanasiev, md, phd stanford health care, department of dermatology, 430 broadway, redwood city, ca 94063 tel: (650) 723-6316 email: olga54@gmail.com references: 1. lim hw, collins sab, resneck js, et al. the burden of skin disease in the united states. j am acad dermatol. 2017;76(5):958-972.e2. doi:10.1016/j.jaad.2016.12.043 2. rappleye e. new-patient wait times for dermatologists in 15 major cities. https://www.beckershospitalreview.com/hospitalphysician-relationships/new-patient-wait-timesfor-dermatologists-in-15-major-cities.html. accessed april 14, 2019. 3. face s, dalton s. consistency of total body surface area assessment in severe burns: implications for practice. emerg med australas ema. 2017;29(4):429-432. doi:10.1111/17426723.12806 4. bożek a, reich a. the reliability of three psoriasis assessment tools: psoriasis area and severity index, body surface area and physician global assessment. adv clin exp med off organ wroclaw med univ. 2017;26(5):851-856. doi:10.17219/acem/69804 5. spuls pi, lecluse lla, poulsen m-lnf, bos jd, stern rs, nijsten t. how good are clinical severity and outcome measures for psoriasis?: quantitative evaluation in a systematic review. j invest dermatol. 2010;130(4):933-943. doi:10.1038/jid.2009.391 6. gerbens l a. a, prinsen c a. c, chalmers jr, et al. evaluation of the measurement properties of symptom measurement instruments for atopic eczema: a systematic review. allergy. 2017;72(1):146-163. doi:10.1111/all.12959 7. swerlick ra, zhang c, patel a, chren mm, chen s. the skindex-mini: a streamlined qol measurement tool suitable for routine use in clinic. j am acad dermatol. december 2018. doi:10.1016/j.jaad.2018.12.035 8. armstrong a, puig l, langley r, et al. validation of psychometric properties and development of response criteria for the psoriasis symptoms and signs diary (pssd): results from a phase 3 clinical trial. j dermatol treat. 2019;30(1):27-34. doi:10.1080/09546634.2017.1364694 9. mhealth economics research program. www.research2guidance.com. www.research2guidance.com. published 2016. accessed april 21, 2019. 10. guido n, hagstrom el, ibler e, et al. a novel total body digital photography smartphone application designed to detect and monitor skin lesions: a pilot study. j surg dermatol. 2018;3(2). doi:10.18282/jsd.v3.i2.177 11. genes n, violante s, cetrangol c, rogers l, schadt ee, chan y-fy. from smartphone to ehr: a case report on integrating patientgenerated health data. npj digit med. 2018;1(1):16. doi:10.1038/s41746-018-0030-8 12. final policy, payment, and quality provisions changes to the medicare physician fee schedule for calendar year 2019 | cms. https://www.cms.gov/newsroom/fact-sheets/finalpolicy-payment-and-quality-provisions-changesmedicare-physician-fee-schedule-calendar-year. accessed april 15, 2019. mailto:olga54@gmail.com skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 563 short communication disseminated hsv-2 infection in a person living with hiv (plwh) ellen wu, ba1, simran chadha, bs1, karen krueger, md2, cuong v nguyen3, lauren guggina, md4 1 northwestern university feinberg school of medicine, chicago, il 2 division of infectious diseases, department of medicine, northwestern university feinberg school of medicine, chicago, il 3 department of dermatology, northwestern university feinberg school of medicine, chicago, il 4 department of dermatology, brigham and women’s hospital, harvard medical school, boston, ma a woman in her 20s with a past medical history of human immunodeficiency virus (hiv) and genital ulcer disease (gud) presented with progressively pruritic, painful, and purulent cutaneous ulcers. her hiv was inconsistently treated with antiretroviral therapy (art) and her gud was managed with intermittent courses of oral valacyclovir for presumed herpes simplex virus (hsv) infection. two months prior to presentation, she was admitted for an eruption involving the pelvis and torso. her eruption was positive for hsv-2 by viral pcr. labs showed an hiv viral load (vl) of 86,184 copies/ml and a cd4 count of 9mm3, consistent with acquired immunodeficiency syndrome (aids). she was treated with 5 days of iv acyclovir and discharged with daily art and 10 days of oral valacyclovir (1g bid). upon presentation to our hospital, she endorsed adherence to her medications with progressive skin erosions, new mild bilateral hearing loss, fevers, and weight loss. physical examination revealed numerous large ulcerations with scalloped borders and a yellow-pink bases of the face, back, perianal region (figure 1), and purulent ulcerations of the bilateral ears (figure 2). laboratory results showed a suppressed hiv viral load of <20 copies/ml and a cd4 count of 13mm3. figure 1. skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 564 figure 2. a swab from her facial glabellar lesion was positive for hsv-2 by viral pcr. viral culture confirmed hsv-2 infection, but susceptibilities could not be obtained. culture of auricular fluid grew staphylococcus aureus, group c betahemolytic streptococcus, and mixed anaerobes. magnetic resonance imaging of the head was negative for mastoiditis. a diagnosis of disseminated hsv-2 with bacterial otitis externa was made. we suspect immune reconstitution inflammatory syndrome (iris) was responsible for her exuberant hsv-2 presentation in the setting of appropriate treatment and a rapid decline in hiv vl. she received 9-days of iv acyclovir and transitioned to oral valacyclovir as her lesions improved. she was continued on art and initiated on prolonged antibiotics with resolution of her otitis externa. at five months post-discharge, her skin lesions were resolved and she continues on treatment dose valacyclovir. hsv-2 is the leading cause of gud, classically manifesting as painful clustered vesicles or erosions on an erythematous base.1 eruptions favor mucocutaneous surfaces, and recurrences are common due to the establishment of neuronal latency in the dorsal root ganglion.1 persons living with hiv (plwh) have an increased risk for severe reactivation with atypical morphologies. higher vl’s and lower cd4 counts correlate with increased frequency, duration, and severity of flares.2 in addition to the large ulcerations seen in our patient, fissures, hypertrophic masses, verrucous growths, and pseudotumors have been described in plwh.1 initiation of art in critically immunosuppressed plwh can cause immune dysregulation and paradoxically amplify opportunistic infections, inflammatory conditions, and autoimmune diseases – a phenomenon called iris.3 dermatological manifestations comprise approximately half of reported iris events.4 these include mycobacterial abscesses, sarcoid-associated erythema nodosum, and kaposi sarcoma.5 notably, up to 11% of patients started on art can have hsv reactivation,3 and while oftentimes mild, these cutaneous presentations can be lifethreatening.4 this case demonstrates a striking example of iris requiring extended, multidisciplinary management. conflict of interest disclosures: none funding: none corresponding author: lauren guggina, md 221 longwood ave boston, ma 02115 skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 565 email: lguggina@bwh.harvard.edu references: 1.mosunjac m, park j, wang yf, et al. genital and perianal herpes simplex simulating neoplasia in patients with aids. aids patient care and stds 2009; 23(3): 153-8. 2.severson jl, tyring sk. relation between herpes simplex viruses and human immunodeficiency virus infections. arch dermatol 1999; 135(11): 1393-7. 3.tobian aa, grabowski mk, serwadda d, et al. reactivation of herpes simplex virus type 2 after initiation of antiretroviral therapy. j infect dis 2013; 208(5): 839-46. 4.lehloenya r, meintjes g. dermatologic manifestations of the immune reconstitution inflammatory syndrome. dermatol clin 2006; 24(4): 549-70, vii. 5.huiras e, preda v, maurer t, whitfeld m. cutaneous manifestations of immune reconstitution inflammatory syndrome. curr opin hiv aids 2008; 3(4): 453-60. skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 350 brief articles long term follow up of cutaneous sinus histiocytosis (rosai-dorfman disease) andrew sequeira1, mario sequeira, md2 1brevard skin and cancer center, rockledge, fl 2dept. of dermatology and cutaneous surgery, university of miami, miami, florida. sinus histiocytosis with massive lymphadenopathy also known as rosaidorfman disease was originally described in 1969.1 it is a histiocytic proliferative disorder characterized by painless lymphadenopathy, fever, leukocytosis, elevated sedimentation rate and igg polyclonal hypergammaglobulinemia.3 extranodal sites can be affected in 43% of cases with the skin and upper respiratory track most commonly represented.4 the skin may be the only organ affected in about 10% of cases without lymphadenopathy and may represent a distinct clinical entity.4,5 a 65-year-old man presented with a reddish brown papule of the right shoulder of several weeks duration in november 2002. the lesion was asymptomatic and he denied any systemic symptoms. full skin physical exam was unremarkable and no lymphadenopathy was identified. the patient's only pertinent past medical history included hypertension, hyperlipidemia, folliculitis and nonmelanoma skin cancer. a tangential scoop biopsy of the site demonstrated a nodular, diffuse mixed infiltrate composed of sheets of large tissue macrophages that contained abundant eosinophilic cytoplasm. many of these macrophages contained phagocytized lymphocytes (figure 1). the infiltrate was admixed with numerous lymphocytes and plasma cells. eosinophils were not identified. special stains demonstrated positive strong staining of the large macrophages with s-100 protein stain. in addition, the macrophages stained positive for cd-68 and negative for cd-1a. special abstract rosai-dorfman disease is a benign histiocytic proliferative disorder of unknown etiology with cutaneous variants clinically presenting with painless cervical lympadenopathy, fever, leukocytosis and other systemic findings.1 although the skin is the most common extranodal site, rare purely cutaneous forms of the disease exist and diagnosing such cases rests solely on histopathologic findings.2 we report a case with a fifteen year follow up period of this uncommon disorder and describe its clinical course marked by multiple episodic recurrences. introduction case report skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 351 stains for mycobacteria (afb) were negative. the histologic changes together with the results of special stains suggested rosai-dorfman disease. initial workup included a negative serum immune electrophoresis, positive epsteinbarr viral capsid antigen igg but negative igm. complete blood count was normal, blood urea nitrogen was slightly elevated at 23 (reference range 7.0 to 20 mg/dl) as well as creatinine at 1.6 (reference range 0.5 to 1.5 mg/dl). the lesion resolved following biopsy but over the subsequent years of follow up similar localized lesions formed on the left upper arm (9/2003, 6/2007), right posterior upper arm (6/2007), mid posterior neck (7/2011), right neck (11/2015), left mid chest (11/2015), right mid back (4/2016), left mid lateral back (4/2017), and right chest (11/2017). all lesions were confirmed by biopsy and treated with localized excisional biopsies. in our patient, all new lesions were morphologically alike (reddish brown firm papules) and isolated (figures, 2,3). during this long follow up period the patient has remained free of systemic symptoms and has never developed lymphadenopathy. figure 1. emperipolesis or phagocytosis of intact lymphocytes by plasma cells (h & e; magnification x 400). figure 2. left mid superior chest reddish brown papule figure 3. left mid lateral back papule a review of 22 cases with purely cutaneous rosai-dorfman disease documented an older age of onset (median, 43.5 years) with an increased female predominance and most commonly affecting asian and caucasian individuals.6 the clinical morphology of the lesions is nonspecific. the condition is self-limited and of unknown etiology and lesions may be present for months or years and may spontaneously regress. on histology dense histiocytic infiltrates with large vesicular nuclei with prominent nucleoli and eosinophilic cytoplasm which stain positive for s-100, discussion skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 352 cd-68 and stain negative for cd-1a are seen.7 emperipolesis or phagocytosis by histiocytes of lymphocytes, neutrophils, polymorphonuclear cells or plasma cells is a characteristic finding.7 various treatments with varying success have been attempted for cutaneous lesions including: cryotherapy, carbon dioxide laser, cortico-steroids (topically, orally and intralesionally), surgical excision, radiotherapy, dapsone, acitretin, imatinib and thalidomide.8 a conservative treatment approach is often appropriate.9 in the current case new lesions were treated with localized excisional biopsies successfully. we present a case with a 15 year follow up of episodically recurrent cutaneous rosaidorfman disease. our case illustrates the fact that this disease can have a benign clinical course without ever developing lymphadenopathy or systemic symptoms. this case with its unique long term follow up period adds evidence that cutaneous rosaidorfman disease is a distinct clinical disorder compared to cases of sinus histiocytosis with massive lymphadenopathy with secondary cutaneous involvement. patients with cutaneous rosai-dorfman disease should be followed closely and managed conservatively in the absence of systemic symptoms. conflict of interest disclosures: none funding: none corresponding author: mario sequeira, md 1286 s. florida avenue, rockledge, fl 32955 321-636-7780 masequeira@cfl.rr.com references: 1. rosai j, dorfman rf. sinus histiocytosis with massive lymphadenopathy. a newly recognized benign clinicopathologic entity. arch pathol. 1969;87:63-70. 2. stefanato cm, ellerin ps, bhawan j. cutaneous sinus histiocytosis (rosai-dorfman disease) presenting clinically as vasculitis. j am acad dermatol. 2002;46:775-778. 3. goodman wt, barrett tl. histiocytoses. in: bologna jl, jorizzo jl, rapinin rp, eds. dermatology. vol 2. london; new york: mosby;2003:1429-1445. 4. traboulsi d. robertson l. rosai-dorfman disease presenting as chronic sinusitis and joint pain with associated facial plaques. j am acad dermatol. 2017;76:ab 222. 5. mirvish e, geskin l, pomerantz r. a case of cutaneous rosai-dorfman disease. j am acad dermatol. 2013;68:ab 38. 6. brenn t, calonje e, granter sr, leonard n, grayson w, fletcher cd, mckee ph. cutaneous rosai-dorfman disease is a distinct clinical entity. am j dermatopathol. 2002;24:385-391. 7. miceli a, cleaver n, spizuoco a. rosai-dorfman disease. cutis. 2015;96:16, 39-40. 8. khan a, musbahi e, suchak r, mehta rk, khorshid sm, ozua p. cutaneous rosaidorfman disease treated by surgical excision and a review of the literature. j am acad dermatol. 2015;72:ab 259. 9. chinthapali s, cerio r, harwood c. cutaneous rosai-dorfman disease: a rare clinical entity. j am acad dermatol. 2017;76:ab 91. conclusion mailto:masequeira@cfl.rr.com skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 148 rising derm stars® impact of consumer preferences, product characteristics, and unregulated marketing claims on online sunscreen purchases giselle prado md1, ashley e ederle ba, shawhin rk shahriari md, ms, ryan svoboda md, ms, aaron farberg md, darrell rigel md, ms 1national society for cutaneous medicine, new york, ny background/objectives: sunscreens, unlike prescription medications are purchased by consumers directly from retailers. the proportion of online sunscreen sales is increasing. it is therefore important for dermatologists to know what factors influence online sunscreen purchases to optimize appropriate recommendations. methods: this is a cohort study of publicly available data from “amazon best sellers in sunscreen” list. variables collected included cost, formulation, product claims, ingredients, consumer ratings, and number of reviews. ordinal logistic regression was used to analyze the impact of collected variables on position on the best-seller list. results: 96 of the 100 search results could be defined as actual sunscreens with a total of 41,788 reviews. the median price per ounce was $3.02 (range $0.34-$309.18). the most popular formulations were lotions (68.8%), continuous sprays (17.7%), sticks (4.2%), and lip balm (4.2%). sun protection factor (spf) 50 (36.5%) and spf 30 (28.1%) were the most purchased levels of sun protection. inorganic and organic sunscreen agents were present in 41.7% and 75% of the top 100 selling sunscreen products, respectively. the most common claim was “non-greasy” found in 57.3% of sunscreens. for 26 product non-regulated claims analyzed, the mean number of claims per sunscreen was 5.2. using an ordinal regression model, the following factors were found to significantly influence sunscreen sales: number of reviews, the claim prevents skin cancer and early aging, and the presence of 6 or more claims. conclusion: multiple sunscreen options exist for consumers with varying price points, active ingredients, and formulations. consumers who purchase online prefer sunscreens with a higher number of reviews and more marketing claims. fda regulated claims such as “prevents skin cancer and early aging,” do not appear as important in this purchasing cohort. to facilitate usage, dermatologists should be cognizant of factors that influence sunscreen selection among this group. eric l. simpson, md, mcr,1 leon kircik, md,2 andrew blauvelt, md, mba,3 michael e. kuligowski, md, phd, mba,4 may e. venturanza, md,4 kang sun, phd,4 lawrence f. eichenfield, md5 introduction ● atopic dermatitis (ad) is a highly pruritic inflammatory skin disease1 ● the severity of ad is often stratified using objective (investigator’s global assessment [iga], eczema area and severity index [easi], body surface area [bsa]) and subjective (eg, itch numerical rating scale [nrs]) assessment tools2-4 ● topical therapies are the standard of care for most patients with ad5 – for patients with more severe ad, systemic therapies may be considered as monotherapy or in combination with topical therapies6 – failure of topical therapies represents one factor when considering systemic therapy; it is not known whether new, more effective nonsteroidal therapies could prevent some patients from starting systemic therapy ● ruxolitinib cream is a topical formulation of ruxolitinib, a selective inhibitor of janus kinase (jak) 1/jak27 ● in two phase 3 randomized studies of identical design (true-ad1 [nct03745638] and true-ad2 [nct03745651]), ruxolitinib cream demonstrated anti-inflammatory activity with antipruritic action vs vehicle and was well tolerated in patients with ad7 objective ● to evaluate the long-term safety and disease control of ruxolitinib cream in a subpopulation of patients with more severe ad at baseline methods study design and patients ● eligible patients were aged ≥12 years with ad for ≥2 years and had an iga score of 2 or 3 and 3%–20% affected bsa, excluding scalp ● key exclusion criteria were unstable course of ad, other types of eczema, immunocompromised status, use of ad systemic therapies during the washout period and during the study, use of ad topical therapies (except bland emollients) during the washout period and during the study, and any serious illness or medical condition that could interfere with study conduct, interpretation of data, or patients’ well-being ● true-ad1 and true-ad2 had identical study designs (figure 1) – in both studies, patients were randomized (2:2:1) to 1 of 2 ruxolitinib cream strength regimens (0.75% twice daily [bid], 1.5% bid) or vehicle cream bid for 8 weeks of double-blinded continuous treatment (vehiclecontrolled [vc] period); patients were instructed to continue treating lesions even if they improved – patients on ruxolitinib cream subsequently continued treatment for 44 weeks (long-term safety [lts] period); patients initially randomized to vehicle were rerandomized 1:1 (blinded) to either ruxolitinib cream regimen ■ during the lts period, patients were instructed to treat skin areas with active ad only and stop treatment 3 days after clearance of lesions; patients were to restart treatment with ruxolitinib cream at the first sign of recurrence figure 1. study design recurrence of lesions clearance of lesions patients initially randomized to rux remain on their regimen patients on vehicle rerandomized 1:1 to 0.75% rux bid or 1.5% rux bid 1.5% rux bid (n=~240 in each study) 0.75% rux bid (n=~240 in each study) patients randomized 2:2:1 vehicle bid (n=~120 in each study) rux† visits every 4 weeks week 52day 1 week 8 vehicle-controlled period • continuous treatment for 8 weeks • rescue treatment not permitted long-term safety period • treat as needed for 44 weeks • stop treatment 3 days after lesion clearance • rescue treatment not permitted ad, atopic dermatitis; bid, twice daily; bsa, body surface area; rux, ruxolitinib cream. † patients self-evaluated recurrence of lesions between study visits and treated lesions with active ad (≤20% bsa). if lesions cleared between study visits, patients stopped treatment 3 days after lesion disappearance. if new lesions were extensive or appeared in new areas, patients contacted the investigator to determine if an unscheduled additional visit was needed. ● the definition of more severe ad (iga score of 3, easi ≥16, and affected bsa ≥10% at baseline) was based on iga, easi, and bsa thresholds for clinical trials of systemic therapies (ie, dupilumab8 and oral jak inhibitors9-11) – other definitions of more severe ad included in this analysis were bsa ≥10% alone and iga=3 alone, as well as combined iga=3, easi ≥16, bsa ≥10%, and itch nrs score ≥4 at baseline assessments ● disease control was assessed by the proportion of patients who achieved no or minimal skin lesions (iga score of 0 or 1 [clear or almost clear skin]) and mean percentage of bsa affected by ad at each visit (every 4 weeks) during the lts period ● safety and tolerability assessments included the frequency of reported treatment-emergent adverse events (teaes), treatment-related adverse events, and adverse events (aes) leading to treatment discontinuation statistical analyses ● all analyses were conducted using the pooled data from both studies – the disease control analysis included patients who remained on their initial ruxolitinib cream strength regimen from the vc period through the lts period; data are reported as observed – the safety analysis included patients who applied ruxolitinib cream in any period (vc or lts) ● data were summarized using descriptive statistics results patients ● a total of 1249 patients (median age, 32 years) were randomized in the vc period ● distribution of baseline demographics and clinical characteristics of all randomized patients was similar across treatment groups (table 1) table 1. patient demographics and baseline clinical characteristics characteristic vehicle (n=250) 0.75% rux (n=500) 1.5% rux (n=499) total (n=1249) age, median (range), y 34.0 (12–82) 33.0 (12–85) 31.0 (12–85) 32.0 (12–85) female, n (%) 159 (63.6) 304 (60.8) 308 (61.7) 771 (61.7) race, n (%) white 170 (68.0) 345 (69.0) 355 (71.1) 870 (69.7) black 61 (24.4) 118 (23.6) 113 (22.6) 292 (23.4) asian 10 (4.0) 16 (3.2) 20 (4.0) 46 (3.7) other 9 (3.6) 21 (4.2) 11 (2.2) 41 (3.3) region, n (%) north america 172 (68.8) 342 (68.4) 341 (68.3) 855 (68.5) europe 78 (31.2) 158 (31.6) 158 (31.7) 394 (31.5) bsa, mean (sd), % 9.6 (5.5) 10.0 (5.3) 9.6 (5.3) 9.8 (5.4) easi, mean (sd) 7.8 (4.8) 8.1 (4.9) 7.8 (4.8) 8.0 (4.8) iga, n (%) 2 64 (25.6) 125 (25.0) 123 (24.6) 312 (25.0) 3 186 (74.4) 375 (75.0) 376 (75.4) 937 (75.0) itch nrs score, mean (sd) 5.1 (2.4) 5.2 (2.4) 5.1 (2.5) 5.1 (2.4) ≥4, n (%) 159 (63.6) 324 (64.8) 315 (63.1) 798 (63.9) duration of disease, median (range), y 16.5 (0.8–79.1) 15.1 (0.1–68.8) 16.1 (0–69.2) 15.8 (0–79.1) facial involvement, n (%)* 93 (37.2) 195 (39.0) 197 (39.5) 485 (38.8) number of flares in last 12 mo, mean (sd)* 7.3 (25.7) 5.2 (6.7) 6.0 (17.6) 5.9 (16.5) bsa, body surface area; easi, eczema area and severity index; iga, investigator’s global assessment; nrs, numerical rating scale; rux, ruxolitinib cream. * patient reported. ● among patients with a baseline iga score of 3, easi ≥16, and bsa ≥10% in the pooled population, 31 and 28 patients continued from the vc to the lts period in the 0.75% and 1.5% ruxolitinib cream arms, respectively, and were evaluated for disease control – 39 and 36 patients applied 0.75% or 1.5% ruxolitinib cream, respectively, in either study period (vc or lts) and were evaluated for safety efficacy ● a substantial proportion of patients achieved clear or almost clear skin (iga 0/1) during the lts period (figure 2); data were similar when different definitions were used to define more severe ad (table 2) figure 2. proportion of patients with clear or almost clear skin (iga 0/1) in the vc and lts periods in patients with iga=3, bsa ≥10%, and easi ≥16 at baseline† pa tie nt s w ith c le ar o r a lm os t c le ar s ki n (ig a of 0 o r 1 ), % 0 20 40 80 100 60 0 52 time, wk vc lts 0.75% rux 1.5% rux n n 4 32 30 8 31 28 12 31 27 16 30 27 20 31 26 24 29 23 28 28 24 32 26 22 36 29 24 40 30 24 44 30 23 48 30 21 30 23 66.7 78.3 35.5 43.8 58.1 48.4 63.3 64.5 72.4 71.4 76.9 82.8 73.3 66.7 66.7 27.6 50.0 67.9 74.1 66.7 69.2 78.3 70.8 68.2 62.5 79.2 91.3 71.4 iga, investigator’s global assessment; lts, long-term safety; rux, ruxolitinib cream; vc, vehicle controlled. † the vc period included up to week 8, and the lts period included weeks 8–52. data for week 8 are from the vc period. table 2. summary of patients achieving iga 0/1 during the lts period using different criteria to define more severe ad at baseline criteria for more severe ad week, % 12 16 20 24 28 32 36 40 44 48 52 bsa ≥10%* 0.75% rux 54.5 60.2 59.5 65.6 66.0 66.9 69.8 68.5 69.9 70.5 71.1 1.5% rux 68.0 66.7 69.6 69.2 67.6 65.8 67.1 70.1 72.3 69.1 68.7 iga=3† 0.75% rux 57.5 64.0 64.9 66.8 68.0 70.2 72.5 72.8 72.1 72.2 75.5 1.5% rux 66.9 68.5 70.8 72.2 72.8 70.4 72.9 74.0 75.8 73.6 74.9 iga=3, easi ≥16, bsa ≥10%, itch nrs ≥4‡ 0.75% rux 43.5 60.9 65.2 66.7 65.0 73.7 85.7 72.7 59.1 59.1 63.6 1.5% rux 68.8 62.5 53.3 61.5 57.1 61.5 57.1 71.4 92.3 66.7 69.2 ad, atopic dermatitis; bsa, body surface area; easi, eczema area and severity index; iga, investigator’s global assessment; lts, long-term safety; nrs, numerical rating scale; rux, ruxolitinib cream. * n=182/n=182 for 0.75%/1.5% rux at the start of the lts period. † n=309/n=328 for 0.75%/1.5% rux at the start of the lts period. ‡ n=23/n=17 for 0.75%/1.5% rux at the start of the lts period. ● percentage of bsa affected by ad is shown in figure 3; data were similar when different definitions were used to define more severe ad (table 3) figure 3. mean percentage of bsa affected by ad in the vc and lts periods in patients with iga=3, easi ≥16, and bsa ≥10% at baseline† m ea n to ta l a ffe ct ed b sa , % 0 4 8 2 6 18 20 16 12 14 10 0 52 time, wk vc lts 0.75% rux 1.5% rux 33 32 n n 4 32 30 8 31 28 12 31 27 16 30 27 20 31 26 24 29 23 28 28 24 32 27 22 36 29 24 40 30 24 44 30 23 48 30 21 30 23 16.8 11.1 8.1 5.7 5.5 5.5 3.5 3.2 3.7 3.1 3.0 4.1 4.1 3.6 3.8 18.0 10.0 6.5 5.2 4.7 4.8 3.8 3.9 3.8 3.9 3.2 2.7 2.6 3.1 2.5 ad, atopic dermatitis; bsa, body surface area; easi, eczema area and severity index; iga, investigator’s global assessment; lts, long-term safety; rux, ruxolitinib cream; vc, vehicle controlled. † the vc period included up to week 8, and the lts period included weeks 8–52. data for week 8 are from the vc period. table 3. summary of mean percentage of bsa affected by ad during the lts period using different criteria to define more severe ad at baseline criteria for more severe ad week, mean % 12 16 20 24 28 32 36 40 44 48 52 bsa ≥10%* 0.75% rux 5.0 4.2 3.3 3.2 3.3 3.1 2.9 3.0 2.9 3.1 2.7 1.5% rux 3.2 3.0 2.6 2.7 2.4 2.9 2.3 2.2 2.1 2.1 2.2 iga=3† 0.75% rux 3.4 3.0 2.3 2.4 2.4 2.2 2.2 2.2 2.2 2.3 2.0 1.5% rux 2.4 2.3 2.0 2.0 1.9 2.1 1.7 1.7 1.6 1.7 1.6 iga=3, easi ≥16, bsa ≥10%, itch nrs ≥4‡ 0.75% rux 5.6 4.5 3.5 3.3 4.2 3.4 2.6 3.7 3.8 3.9 3.6 1.5% rux 4.9 4.6 3.5 3.8 3.6 3.1 3.0 2.4 2.1 2.7 2.0 ad, atopic dermatitis; bsa, body surface area; easi, eczema area and severity index; iga, investigator’s global assessment; lts, long-term safety; nrs, numerical rating scale; rux, ruxolitinib cream. * n=182/n=182 for 0.75%/1.5% rux at the start of the lts period. † n=309/n=328 for 0.75%/1.5% rux at the start of the lts period. ‡ n=23/n=17 for 0.75%/1.5% rux at the start of the lts period. safety ● in the overall population, the most common teaes through week 52 were upper respiratory tract infection, nasopharyngitis, and headache – no aes suggestive of a relationship to systemic exposure were observed ● ruxolitinib cream was well tolerated and the frequency of application site reactions was low in this subset of patients with more severe ad (table 4) table 4. adverse events among patients with iga=3, easi ≥16, and bsa ≥10% at baseline who applied ruxolitinib cream in the phase 3 studies (vc or lts periods) n (%) 0.75% rux (n=39) 1.5% rux (n=36) patients with teae 28 (71.8) 24 (66.7) patients with application site reaction 1 (2.6) 2 (5.6) patients with trae 6 (15.4) 6 (16.7) patients who discontinued due to a teae 0 0 patients with serious teae* 1 (2.6) 1 (2.8) lts, long-term safety; rux, ruxolitinib cream; teae, treatment-emergent adverse event; trae, treatment-related adverse event; vc, vehicle controlled. * none were considered related to treatment with ruxolitinib cream. conclusions ● the subset of patients meeting various thresholds for more severe disease at baseline achieved effective long-term disease control with ruxolitinib cream monotherapy during the 52-week study period ● ruxolitinib cream was well tolerated in the long-term setting in this subset of patients who may be eligible for both systemic and topical therapies ● these data suggest that ruxolitinib cream may delay or prevent the need for systemic therapy in a subset of patients with more severe ad – although these patients met various thresholds for more severe disease at baseline, failure of topical therapy was not a requirement for entering the studies disclosures els is an investigator for abbvie, eli lilly, galderma, kyowa hakko kirin, leo pharma, merck, pfizer, and regeneron and is a consultant with honorarium for abbvie, eli lilly, forte bio, galderma, incyte corporation, leo pharma, menlo therapeutics, novartis, pfizer, regeneron, sanofi genzyme, and valeant. lk has served as an investigator, consultant, or speaker for abbvie, amgen, anaptys, arcutis, dermavant, eli lilly, glenmark, incyte corporation, kamedis, leo pharma, l’oreal, menlo therapeutics, novartis, ortho dermatologics, pfizer, regeneron, sanofi, sun pharma, and taro. ab has served as a scientific advisor and/or clinical study investigator for abbvie, abcentra, aligos, almirall, amgen, arcutis, arena, aslan, athenex, boehringer ingelheim, bristol myers squibb, dermavant, eli lilly and company, evommune, forte, galderma, incyte corporation, janssen, landos, leo pharma, novartis, pfizer, rapt, regeneron, sanofi genzyme, sun pharma, and ucb pharma. mek was an employee and shareholder of incyte corporation at the time of development of the original presentation. mev and ks are employees and shareholders of incyte corporation. lfe has served as an investigator, consultant, speaker, or data safety monitoring board member for abbvie, almirall, arcutis, asana, dermavant, eli lilly, forte biosciences, galderma, ichnos/glenmark, incyte corporation, janssen, leo pharma, novartis, ortho dermatologics, otsuka, pfizer, regeneron, and sanofi genzyme. acknowledgments the authors thank the patients, investigators, and investigational sites whose participation made the study possible. support for this study was provided by incyte corporation (wilmington, de, usa). writing assistance was provided by tania iqbal, phd, an employee of icon (north wales, pa, usa), and was funded by incyte corporation. references 1. langan sm, et al. lancet. 2020;396(10247):345-360. 2. chopra r, et al. br j dermatol. 2017;177(5):1316-1321. 3. vakharia pp, et al. br j dermatol. 2018;178(4):925-930. 4. gooderham mj, et al. j cutan med surg. 2018;22(suppl 1):10s-16s. 5. eichenfield lf, et al. j am acad dermatol. 2014;70(2):338-351. 6. simpson el, et al. j am acad dermatol. 2017;77(4):623-633. 7. papp k, et al. j am acad dermatol. 2021;85(4):863-872. 8. simpson el, et al. n engl j med. 2016;375(24):2335-2348. 9. simpson el, et al. br j dermatol. 2020;183(2):242-255. 10. guttman-yassky e, et al. j allergy clin immunol. 2020;145(3):877-884. 11. silverberg ji, et al. jama dermatol. 2020;156(8):863-873. 1oregon health & science university, portland, or, usa; 2icahn school of medicine at mount sinai, new york, ny, usa; 3oregon medical research center, portland, or, usa; 4incyte corporation, wilmington, de, usa; 5departments of dermatology and pediatrics, university of california san diego, san diego, ca, usa long-term safety and disease control with ruxolitinib cream in patients with more severe atopic dermatitis: pooled results from two phase 3 studies presented at the fall clinical dermatology conference las vegas, nv • october 21–24, 2021 to download a copy of this poster, scan code. patient tolerability of tazarotene foam, 0.1%, and impact on patient compliance treatment of palmo-plantar keratoderma of unna-thost with tazarotene foam 0.1% farooq lateef md, faad; hanna lateef h our case illustrates the difficulties in diagnosing a disease that predisposes the patient to secondary fungal infections that can obscure the underlying diagnosis at initial presentation.5, 6 once the fungal infection was treated and the underlying diagnosis was established, a topical retinoid was shown to be very effective. treatment of keratoderma of unna-thost consists of addressing the hyperhidrosis and secondary infections followed by treating the disease itself. various treatments have been tried, including topical keratolytics(such as salacylic acid, urea, lactic acid), topical retinoids(such as tretinoin, adapalene), but many cases in the literature report best results with oral retinoids(such as acitretin and isotretinoin).5,6,7 given the significant side-effects of oral retinoids, the patient refused them. tazarotene foam, with its decreased absorption into the bloodstream8, proved to be a good choice. the degree and speed of initial improvement, and the long term maintenance of benefit were most gratifying. tazarotene cream has been used with some success in palmoplantar psoriasis.9 now that tazarotene is available in a foam formulation, and, in our case has shown excellent tolerability and therapeutic value, it may be worthwhile to revisit treatment of hyperkeratotic states with tazarotene foam. 1. stypczynska e, placek w, zegarska b, czajkowski r. keratination disorders and genetic aspects in palmar and plantar keratodermas. acta dermatovenerol croat 2016;24(2):116-23. 2. umegaki n, nakano o, tamai k, et al. vorner type palmoplantar keratoderma: novel krt9 mutation associated with knuckle-pad like lesions and recurrent mutation causing digital mutilation. br j dermatol 2011;165:199-201. 3. kuster w, reis a, hennies hc. epidermolytic palmoplantar keratoderma of vorner: reevaluation of vorner’s original family and identification of a novel keratin 9 mutation. arch dermatol res 2002;294:268-72. 4. hinterberger l, pfohler c, vogt t, muller csl. diffuse epidermolytic palmoplantar keratoderma (unna-thost). bmj case rep 2012; published online nov 9. doi: 10.1136/bcr-2012-006443. 5. maruyama r, katoh t, nishioka k. a case of unna-thost disease accompanied by epidermophyton floccosum infection. j dermatol 1999;26(1):63-6. 6. gambourg np, faergemann j. dermatophytes and keratin in patients with hereditary palmoplantar keratoderma. a mycological study. acta derm venereol 1993;73(6):416-8. 7. wang b, zhang z, huang x, et al. successful treatment of mutilating palmoplantar keratoderma with acitretin capsule and adapalene gel: a case report with review of the literature. j eur acad dermatol venereol 2016;30(1):169-72. 8. jarratt m, werner cp, saenz aba. tazarotene foam versus tazarotene gel : a randomized relative bioavailability study in acne vulgaris. clin drug investig 2013;33:283-9. 9. mehta bh, amladi st. evaluation of topical 0.1% tazarotene cream in the treatment of palmoplantar psoriasis: an observer-blinded randomized controlled study 2011;56(1):40-3. keratoderma of unna-thost is an autosomal dominant genetic disorder. it presents with thick keratotic plaques of the palms and soles, often with a red border. hyperhidrosis is a common feature. secondary bacterial and fungal infections can occur, resulting in a chronic malodorous condition that is difficult to live with. 1 in earlier times, keratoderma of vorner was thought to be a different clinical entity. however, genetic studies have confirmed mutations in the keratin 1 and keratin 9 genes in both conditions.2,3 therefore vorner’s keratoderma has been subsumed under the umbrella of unna-thost.4 introduction • a 30 year old hispanic female presented with itchy palms and soles. she gave a history of having some thickening of the palms and soles over many years, but noted worsening of symptoms over the last 2 to 3 weeks. on exam she had red, thick, keratotic and scaly plaques on the palms and soles, with some vesicles and excoriations. her toenails were thickened, with yellow subungual debris. presumptive diagnosis was a severe contact dermatitis versus palmoplantar psoriasis. she was treated with clobetasol foam and urea foam. a north american standard allergen patch test was done, showing a 2+ reaction to cocoamidopropyl betaine. avoidance of the antigen was discussed. nail biopsy showed numerous fungal hyphae on pas stain. • clobetasol foam was discontinued. patient was treated for tinea pedis and tinea ungum. cicloprox lotion and aluminum chloride hexahydrate solution was started, with some improvement. after liver functions were checked, oral terbinafine 250 mg per day was given for three months, with good response. erythema, vesiculation and itch resolved. however, the hyperkeratosis and hyperhidrosis persisted. by this time, patient had conferred with distant family, and noted that a maternal aunt and several other distant relatives also suffered from the same condition. a diagnosis of palmoplantar keratoderma of unna thost was made. patient used combinations of urea foam, aluminum chloride hexahydrate, and cicloprox lotion with tolerable improvement and quality of life. • after 7 years, the patient noted worsening of symptoms, with severe itch, erythema, hyperhidrosis and thick hyperkeratosis. previous therapies were resumed with no success. a skin biopsy showed compact orthokeratin and coarse bundles of collagen in vertical array in the papillary dermis. pas stain for fungus was negative. nail biopsy showed a thickened nail plate, and negative pas for nail fungus. patient was started on clobetasol foam, aluminum chloride hexahydrate solution, and urea foam. • after 2 weeks, urea foam was stopped due to ineffectiveness. tazarotene foam was added. discussion methods references results patient returned in three weeks with near-resolution of all symptoms, claiming she had never been this clear at any time since the disease began. patient had no erythema, minimal hyperhidrosis and minimal scale. the thickened keratotic plaques had dissolved. patient has maintained remission of nearly all symptoms over the last 4 months. 1. this case study and presentation were funded by a grant from mayne pharma. 2. dr. lateef is an associate professor of dermatology at florida state university college of medicine. disclosures after 4 months of treatment with tazarotene foam, 0.1%after 3 weeks of treatment with tazarotene foam, 0.1%prior to treatment with tazarotene foam, 0.1% efficacy and safety of ingenol mebutate in patients with actinic keratosis on face and scalp: subgroup analysis of two vehicle-controlled trials according to age (<65 and ≥65 years) hee j. kim, md1; jes b. hansen, phd2; mads faurby, mph2; meg corliss, phd3; and mark g. lebwohl, md1 1department of dermatology, mount sinai hospital, new york, ny, usa; 2leo pharma a/s, ballerup, denmark; 3leo pharma inc, madison, nj, usa introduction background � actinic keratosis (ak) is a common skin disease typically diagnosed clinically by the presence of thickened, cornified, scaly patches on sunexposed skin � although the frequency of the disease is highest in older individuals, aks are also observed in those who are younger1-4 − in the rcts for ak therapies overall, the average age of participants has been >60 y, although eligibility criteria include age ≥18 y5-9 � the mean age of patients in the rcts of 3-day, ingenol mebutate treatment of the face and scalp was approximately 65 y9 � the effect of age on the efficacy and safety of ak treatment has not been reported and merits investigation objective � a subanalysis of pooled data from phase 3 studies of ingenol mebutate gel 0.015% used for aks on the face and scalp was conducted to assess the effect of age on the efficacy and safety of this treatment9 methods � an age-based subgroup analysis included pooled data from the 2 vehiclecontrolled trials of ingenol mebutate gel 0.015% for the treatment of aks on the face and scalp − clinicaltrials.gov identifier: nct00915551 and nct00916006 � patients were classified into 1 of 2 subgroups based on age, <65 y or ≥65 y � in this post hoc analysis, complete and partial clearance rates were analyzed for each subgroup, with corresponding confidence intervals (cis) derived using the exact binomial method; p-value was based on the chisquare test � for each of the age-based subgroups, the following end points were analyzed descriptively: − percent reduction from baseline in lesion count − mean scores for local skin response (lsr) − number of adverse events (aes) results baseline characteristics � the 2 face and scalp studies included a total of 547 caucasian patients (table 1) − 284 (51.9%) patients were <65 y, and 263 (48.1%) patients were ≥65 y − patients ranged in age from 34 y to 89 y − in the active treatment cohort, the difference in the average age between the 2 subgroups was approximately 18 y � demographic and baseline characteristics were similar between the ingenol mebutate and vehicle cohorts for both age categories table1: demographics and baseline characteristics ingenol mebutate gel 0.015% (n=277) vehicle gel (n=270) <65 y (n=144) ≥65 y (n=133) <65 y (n=140) ≥65 y (n=130) age mean (sd), y 55.7 (6.2) 73.4 (6.3) 56.0 (5.8) 72.7 (5.7) median (range), y 56.0 (34-64) 72.0 (65-88) 57.0 (40-64) 72.0 (65-89) n (%) country australia 14 (9.7) 7 (5.3) 11 (7.9) 9 (6.9) usa 130 (90.3) 126 (94.7) 129 (92.1) 121 (93.1) sex female 29 (20.1) 15 (11.3) 19 (13.6) 19 (14.6) male 115 (79.9) 118 (88.7) 121 (86.4) 111 (85.4) ethnicity caucasian hispanic 0 (0.0) 1 (0.8) 3 (2.1) 0 (0.0) caucasian non-hispanic 144 (100.0) 132 (99.2) 137 (97.9) 130 (100.0) treatment area face 116 (80.6) 104 (78.2) 110 (78.6) 110 (84.6) scalp 28 (19.4) 29 (21.8) 30 (21.4) 20 (15.4) ak clearance � rates of complete and partial clearance were numerically higher in patients <65 y than in those ≥65 y, but the difference was not significant (figure 1) (table 2) � percent reduction from baseline in lesion count was numerically higher in patients <65 y than in those ≥65 y (figure 2) figure 1: age-based subanalysis of ak clearance rates 45.1 5.0 39.1 2.3 0 10 20 30 40 50 60 70 80 90 100 p at ie nt s (% ) complete clearance rate <65 y ≥65 y n=130n=140n=133 ingenol mebutate gel 0.015% vehicle gel p=.309 p=.242 results age-based subanalysis of ak clearance rates n=144 • rates of complete and partial clearance were numerically higher in patients <65 y than in those ≥65 y, but the difference was not significant 5 66.7 8.6 60.9 6.2 0 10 20 30 40 50 60 70 80 90 100 p at ie nt s (% ) partial clearance rate <65 y ≥65 y n=130n=140n=133 ingenol mebutate gel 0.015% vehicle gel p=.318 n=144 p=.449 table 2: age-based subanalysis of complete and partial clearance rates, with variance rate of complete clearance ingenol mebutate gel 0.015% (n=277) vehicle gel (n=270) patients (n) rate; 95% ci (%) or; 95% ci p patients (n) rate; 95% ci (%) or; 95% ci p <65 y (n=144) 65 45.1; 37.0, 53.3 1.28; 0.79, 2.07 .309 <65 y (n=140) 7 5.0; 1.4, 8.6 2.23; 0.56, 8.81 .242 ≥65 y (n=133) 52 39.1; 30.8, 47.4 ≥65 y (n=130) 3 2.3; 0.0, 4.9 rate of partial clearance ingenol mebutate gel 0.015% (n=277) vehicle gel (n=270) patients (n) rate; 95% ci (%) or; 95% ci p patients (n) rate; 95% ci (%) or; 95% ci p <65 y (n=144) 96 66.7; 59.0, 74.4 1.28; 0.79, 2.10 .318 <65 y (n=140) 12 8.6; 3.9, 13.2 1.43; 0.57, 3.62 .449 ≥65 y (n=133) 81 60.9; 52.6, 69.2 ≥65 y (n=130) 8 6.2; 2.0, 10.3 ci=confidence interval; or=odds ratio. figure 2: age-based subanalysis of reduction in ak count from baseline results age-based subanalysis of reduction in ak count from baseline 85.7 0.0 80.0 0.0 0 10 20 30 40 50 60 70 80 90 100 m ed ia n (% ) median reduction from baseline <65 y ≥65 y ingenol mebutate gel 0.015% vehicle gel n=140n=132 n=129n=141 • percent reduction from baseline in lesion count was numerically higher in patients <65 y than in those ≥65 y, but the difference was not significant 7 76.0 16.4 69.1 12.5 0 10 20 30 40 50 60 70 80 90 100 m ea n (% ) mean reduction from baseline <65 y ≥65 y ingenol mebutate gel 0.015% vehicle gel n=140n=132 n=129n=141 tolerability � the intensity and the time course of development and resolution of lsrs in the active treatment and vehicle cohorts were the same in patients <65 y and ≥65 y (figure 3) − assessments occurred on days 1, 4, 8, 15, 29, and 57 figure 3: composite lsr scores results composite lsr scores 8 • the intensity and the time course of development and resolution of lsrs in the active treatment and vehicle cohorts were the same in patients <65 y and ≥65 y ▪ assessments occurred on days 1, 4, 8, 15, 29, and 57 0 1 2 3 4 5 6 7 8 9 10 0 5 10 15 20 25 30 35 40 45 50 55 60 m ea n c om po si te l s r s co re day ingenol mebutate gel 0.015%, <65 y ingenol mebutate gel 0.015%, ≥65 y vehicle gel, <65 y vehicle gel, ≥65 y adverse events � in the ingenol mebutate treatment group, the proportion of patients who had aes was lower in those <65 y (31.8%) than in those ≥65 y (42.3%) (table 3) − among the most frequently reported aes, rates of application-site pain, pruritus, and irritation were lower in the younger subgroup � the rate of serious aes was low in all cohorts, between 1% and 2% in all ingenol mebutate and vehicle groups table 3: any ae, any serious ae, and any type of ae occurring at ≥2.0% in any ingenol mebutate subgroup ingenol mebutate gel 0.015% (n=274) vehicle gel (n=271) <65 y (n=132) ≥65 y (n=142) <65 y (n=130) ≥65 y (n=141) patients n (%) events n patients n (%) events n patients n (%) events n patients n (%) events n any ae 42 (31.8) 76 60 (42.3) 118 28 (21.5) 55 32 (22.7) 52 any serious ae 3 (2.3) 6 3 (2.3) 4 3 (2.1) 4 2 (1.4) 2 type of ae application-site pain 14 (10.6) 19 24 (16.9) 31 1 (0.8) 2 0 (0.0) 0 application-site pruritus 7 (5.3) 7 15 (10.6) 15 1 (0.8) 1 2 (1.4) 2 application-site irritation 1 (0.8) 1 4 (2.8) 4 0 (0.0) 0 0 (0.0) 0 application-site infection 3 (2.3) 3 4 (2.8) 4 0 (0.0) 0 0 (0.0) 0 periorbital edema 4 (3.0) 5 3 (2.1) 3 0 (0.0) 0 0 (0.0) 0 conclusions � there were no significant differences in rates of ak clearance between younger and older patients treated with ingenol mebutate gel 0.015% based on this post hoc analysis of phase 3 studies of the face and scalp − complete clearance rate: 45.1% (<65 y) vs 39.1% (≥65 y) − partial clearance rate: 66.7% (<65 y) vs 60.9% (≥65 y) � reduction from baseline in ak count was also similar for the 2 subgroups − mean reduction: 76.0% (<65 y) vs 69.1% ( ≥65 y) − median reduction: 85.7% (<65 y) vs 80.0% (≥65 y) � no differences between younger and older patients were observed in the severity and time course of resolution of lsrs � the frequency of aes was numerically lower in those <65 y (31.8%) than in those ≥65 y (42.3%) � ingenol mebutate gel 0.015% is an effective and safe treatment option for patients with aks on the face and scalp, regardless of age references 1. zagula-mally zw, rosenberg ew, kashgarian m. cancer. 1974;34:345-349. 2. frost ca, green ac, williams gm. br j dermatol. 1998;139:1033-1039. 3. memon aa, tomenson ja, bothwell j, friedmann ps. br j dermatol. 2000;142:1154-1159. 4. naldi l, chatenoud l, piccitto r, et al. arch dermatol. 2006;142:722-726. 5. lebwohl m, dinehart s, whiting d, et al. j am acad dermatol. 2004;50:714-721. 6. weiss j, menter a, hevia o, et al. cutis. 2002;70(2 suppl):22-29. 7. rivers jk, arlette j, shear n, et al. br j dermatol. 2002;146:94-100. 8. hanke cw, beer kr, stockfleth e, et al. j am acad dermatol. 2010;62:573-581. 9. lebwohl m, swanson n, anderson ll, et al. n engl j med. 2012;15(366):10101019. acknowledgments this study was sponsored by leo pharma inc. poster presented at the winter clinical dermatology conference; koloa, hi; january 18-23, 2019. skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 702 short communications a thousand words for a picture of health amy k. blake, md, ma1 1 the university of north carolina at chapel hill, department of dermatology, chapel hill, nc on april 5, 2021, the ground shifted as the cures act made clinical documentation immediately available to those about whom it was written. the medical record originally facilitated note-taking and teaching, and evolved over time into an instrument of billing and a means of multidisciplinary communication. this shift now positions the medical record to serve as a real-time method of patient communication—whether or not it is well-suited for that task. regardless of our estimation of this shift, it presents an opportunity to consider how our communication skills measure up. we know that effective communication bolsters physician-patient relationships and generates better patient outcomes,1 while words brandished unthinkingly can serve as a vehicle for bias and can negatively affect clinical decision-making.2 physicians use jargon more often than we realize, and we overestimate patients’ understanding of what we say.3 written language poses additional challenges, as it does not permit real-time clarifications or the contextualization of body language.1 furthermore, our scientific writing conventions are not designed for ease of comprehension and likely are inaccessible to the significant proportion of the us population with low literacy and to those for whom english is not a first language.4 dermatologists’ emphasis on precise terminology and dialectical mastery may deepen this challenge. our specialty is inextricably intertwined with language, as dermatology’s gradual emergence as a distinct specialty corresponded with the creation of a greekand latin-based lexicon for organizing and classifying cutaneous disease.5 these linguistic roots remain woven through our modern language, as we command a vocabulary of esoteric synonyms—shall we choose pityriasis rubra pilaris, lichen ruber pilaris, or devergie disease? even a thousand words cannot capture a picture in some cases, it seems. the language we spend years learning to wield—and on which we rely for documentation—undoubtedly is incomprehensible to most. the foreignappearing words may be an insurmountable wall to a patient receiving an unfamiliar diagnosis, and they may turn to less-reliable sources to piece together an understanding of their suffering. our intended meaning may be lost within the words themselves, and with it, the highest potential of our therapeutic relationships. though an initial time investment will be needed, simple adjustments to our documentation could pay dividends. we can code the most specific diagnosis (pruritus sine materia) while documenting an skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 703 assessment and plan in direct, concrete language that limits abbreviations and technical terminology (“itching without rash”). as teachers and mentors, we can incentivize writing that achieves clarity of meaning rather than regurgitation of vocabulary in a scientific construct. and we can self-reflect, regularly examining our own linguistic conventions and habits to ensure these words convey the respect and inclusivity our patients deserve.2 as we navigate this new dimension of physician-patient communication, dermatologists must remain cognizant of the unique challenges posed by our specialized lexicon, as well as the broader one of effectively employing the medical written word. we have a special appreciation and a heavy responsibility for the language we command—let’s seize this opportunity to use it for the greatest good. conflict of interest disclosures: none funding: none corresponding author: amy k. blake, md, ma 410 market st, ste 400 chapel hill, nc 27516 phone: 984-974-3900 email: amy.blake@unchealth.unc.edu references: 1. nguyen tv, hong j, prose ns. compassionate care: enhancing physician-patient communication and education in dermatology: part i: patient-centered communication. j am acad dermatol. mar 2013;68(3):353.e1-8. doi:10.1016/j.jaad.2012.10.059 2. p goddu a, o'conor kj, lanzkron s, et al. do words matter? stigmatizing language and the transmission of bias in the medical record. j gen intern med. 05 2018;33(5):685-691. doi:10.1007/s11606-017-4289-2 3. ross n, hannaway m, keller m. improving doctor-talk: a cross-sectional examination of medical jargon evaluating patient and provider communication discrepancies. journal of the american academy of dermatology. 2017;76(6)(1):ab410. doi:https://doi.org/10.1016/j.jaad.2017.06.083 4. plavén-sigray p, matheson gj, schiffler bc, thompson wh. the readability of scientific texts is decreasing over time. elife. 09 2017;6doi:10.7554/elife.27725 5. santoro r. skin over the centuries. a short history of dermatology: physiology, pathology and cosmetics. medicina historica. 2017;1(2):94-102. skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 568 clinical management recommendations psoriasis therapy beyond biologics connor r. buechler, md1,2, jesse veenstra, md, phd3, linda stein gold, md3 1department of dermatology, university of minnesota, minneapolis, mn 2department of internal medicine, university of minnesota, minneapolis, mn 3department of dermatology, henry ford health system, detroit, mi psoriasis is a chronic, relapsing, immunemediated condition that affects roughly 3% of the us population and an estimated 125 million individuals worldwide. plaque psoriasis is the most common form of the disease, manifesting as well-demarcated scaly erythematous patches and plaques on extensor surfaces, often with intense pruritus. the advent of biologics, including tnf inhibitors, il-12/23 inhibitors, il-17 inhibitors, and il-23 inhibitors, as treatment for psoriasis has heralded an era of remarkably improved therapies, particularly for moderate to severe plaque psoriasis and psoriatic arthritis. however, these medications are not necessarily appropriate or needed for every patient. in this review we will discuss available treatments and pearls regarding nonbiologic options for psoriasis, with a brief review of non-biologic systemic therapies followed by an in-depth discussion of recent advances in topical therapeutics and recommendations as to their inclusion in patient care. as biologic systemic therapies available for the treatment of psoriasis have proliferated in recent years, traditional oral systemic abstract although psoriasis patients have benefited from the advent of biologic treatments over the past two decades, these medications are not appropriate for all patients and can be augmented by additional therapy. differences among the manifold options can be difficult to parse, though essential for matching treatment with an individual patient. uv-light therapies, including both uv-b and psoralen with uv-a light, continue to play an important role in treatment, as do non-biologic systemic options including methotrexate, cyclosporine, apremilast, and acitretin. recent years have seen a dramatic expansion in available topical therapies, the most common modality for the treatment of psoriasis, including new foam, spray, lotion, and cream formulations of topical corticosteroids (tcs) and new fixed-dose combination offerings of tcs with tazarotene and calcipotriene. newer advances, including the oral tyrosine kinase 2 inhibitor deucravacitinib and non-steroidal topicals such as roflumilast, a pde-4 inhibitor, and tapinarof, a first-in-class non-steroidal small-molecule, will soon provide even more options for treatment. it is vital for clinicians to remain aware of this everexpanding armamentarium, allowing for more productive shared decision-making with patients, improved satisfaction, and better disease control. introduction oral systemic treatment skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 569 treatments [table 1] have fallen relatively out of favor. since the approval of apremilast in 2014, there have been no new oral agents approved for the treatment of plaque psoriasis. the side effect profiles of therapies in this category should be carefully considered before initiating therapy. table 1. non-biologic systemic therapies for plaque psoriasis medication treatment success rates* advantages methotrexate 45.2% at week 12 or 163 highly effective therapy at low cost acitretin 47% at week 1246 no immune suppression cyclosporine 50-97% at week 10-1647 excellent bridge to alternative therapy for control of severe disease apremilast 30-40% at week 1611-13 no monitoring needed deucravacitinib† 50.3%-53.6% at week 1616 oral dosing with efficacy approaching injectable biologics *based on reported pasi75 over multiple studies †phase iii trials ongoing, application for regulatory approval pending methotrexate one of the oldest treatments for psoriasis available today and the most commonly prescribed for psoriatic arthritis, methotrexate, is a dihydrofolate reductase inhibitor usually dosed at 15-20 mg once weekly for psoriasis.2 studies have shown that patients achieve at least a 75% improvement in the psoriasis area and severity index (pasi75) at week 12 or 16 in 45.2% of patients as compared to 4.4% with placebo.3 however, use can cause hepatic fibrosis and cirrhosis, irreversible lung injury, bone marrow suppression, renal toxicity, diarrhea and ulcerative stomatitis, birth defects, and predisposition to infections.4 many insurers still require a trial of methotrexate prior to initiation of biologic therapy, and its effectiveness and cost make it a fair option for most patients. cyclosporine the cyclophilic peptide cyclosporine, originally approved for treatment of psoriasis in 1997, acts via calcineurin inhibition and independent dampening of t-cell activation.5 a recent network meta-analysis found that 2.5–5 mg/kg/day for 12–16 weeks results in a pasi90 equivalent to that of methotrexate.6 however, potential adverse effects are also a significant barrier to treatment, including nephrotoxicity, hepatotoxicity, hypertension, paresthesia, hypertrichosis, gingival hyperplasia, electrolyte disturbances, increased risk of infections, and increased risk for skin and lymphoproliferative malignancies.7 cyclosporine is typically used as a bridging therapy to assist with rapid control of severe or poorly controlled psoriasis while another long-term therapy is being initiated. longterm use of cyclosporine beyond 3 months is uncommon and use over 1 year is not recommended. acitretin acitretin is a vitamin a derivative whose mechanism of action involves binding of an intracellular receptor, leading to improved regulation of epidermal proliferation.8 studies of acitretin since its approval for the treatment of psoriasis in 1996 have demonstrated that doses of 25-50 mg/day prove less effective than other traditional systemic agents.9 acitretin use is likewise limited by side effects, including skeletal toxicity, hepatotoxicity, hyperlipidemia, mucocutaneous effects, arthralgia, myalgia, skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 570 and pseudotumor cerebri.10 however, its lack of immunosuppressive side effects makes it a good choice for patients for whom another systemic therapy would not be appropriate. it would not be an appropriate choice in most women of childbearing age, given teratogenic effects that persist for 2-3 years even after cessation of therapy, nor for those with concomitant psa, on which it has no effect.9 apremilast the newest non-biologic systemic therapy for psoriasis, apremilast, is a phosphodiesterase-4 (pde-4) inhibitor that modulates both the immune response and epithelial proliferation.11 studies have shown that 30-40% of patients achieve pasi75 after 16 weeks of treatment with 30 mg twice daily.11-13 use is limited by the most prominent side effects of diarrhea and weight loss, infections, depression, and headache, though no standard blood draws are required for routine monitoring, unlike all other oral options, making it a better choice for those who would be unable to sustain a monitoring visit schedule.10 emerging oral therapies while jak inhibitors such as tofacitinib showed good results in clinical trials, doses needed for control of plaques proved too high, and potential safety issues too significant, to recommend their use in treatment beyond psa.14 although not yet approved by the fda, the oral tyrosine kinase 2 (tyk2) inhibitor deucravacitinib has shown great promise in recent trials. a phase ii trial testing various dosing regimens noted up to 75% pasi75,15 and phase iii trials of 6 mg daily treatment are ongoing, with preliminary data showing superiority to both apremilast and placebo over 16 and 24-week treatment courses.16 although use of phototherapy for the treatment of psoriasis has decreased dramatically since the advent of biologic therapy,1 it remains an important option in the right patient setting. uv-b uv-b light was originally used in broadband form (290-320 nm), but is now almost exclusively used as narrowband (311 nm) light for the treatment of psoriasis, given improved clinical efficacy.17 treatment with uv-b light decreases dna synthesis, inducing apoptosis of pathogenic t-cells and proliferating keratinocytes, as well as causing local and systemic immunosuppression.18 treatment begins at up to 3 times weekly, though can eventually be tapered to twice per week or less. excimer laser/lamp, which uses a monochromatic uv-b source at 308 nm, can be used for highly targeted therapy of individual lesions. puva psoralen and uv-a light (puva) provide a photochemotherapy in which a photosensitizing drug, psoralen, is given either systemically or topically prior to uva (320-400 nm) radiation. similar to uvb treatment, administrations start at 2-3 times weekly, with tapering over the longer term once disease control has been established. although puva has proven more efficacious than uvb for refractory disease,18 concerns over the long-term carcinogenic risk of uva as well as gi distress caused by systemic psoralens tend to limit its usage in the clinic.19 phototherapy skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 571 eighty percent of psoriasis patients are thought to have disease amenable to topical therapy,20 though significant issues in compliance prove to be a formidable barrier to disease control.21 the therapeutic options in this space are constantly advancing [table 2], driven largely by patient dissatisfaction with current options.22 reviewing all available topical therapies is beyond the scope of this brief article, and there are excellent reviews of topical therapies elsewhere in the literature,23,24 so here we will review the most recent advances in the field along with recommendations as to their inclusion in clinical practice. as patient preferences for topical therapies can be heterogeneous and difficult to predict, with many valuing delivery mode more than proven efficacy,25,26 it is imperative that the choice of topical therapy be a collaborative decision. steroidal formulations topical corticosteroids (tcs) have been the cornerstone of psoriasis therapy since the 1950s, largely offered as creams, ointments, and lotions that act through antiinflammatory, antimitotic, immunomodulatory, apoptotic, and vasoconstrictive functions. advances in vehicle technology have allowed for the development of sprays and foams, as well as improvements upon lotion vehicles, all of which can dramatically improve the user experience by leaving less residue and being less bothersome to apply than traditional formulations. betamethasone dipropionate (bd) 0.05%, previously available in ointment, lotion, and cream formulations, is now available as a twicedaily spray, which outperforms vehicle alone and provides relief comparable to the corresponding superpotent lotion, while rating only mid-potency by vasoconstrictive assay, indicating a decreased risk for atrophy, hpa-suppression, and other common tcs side effects.27,28 halobetasol propionate (hp) 0.05%, likewise previously available in ointment, lotion, and cream formulations, is now offered as a twice-daily foam that can provide control of symptoms after a two-week course.29 this foam also appears to show minimal systemic absorption and no hpa axis suppression in those age 12-18, though pediatric use is currently off-label.30 hp is also now available as a 0.01% lotion, one-fifth of the traditional 0.05% concentration, that can be used daily over an extended 8-week treatment course, useful for those patients who desire a more extended therapeutic treatment without sacrificing efficacy.31,32 finally, clobetasol propionate (cp) is newly available as a 0.025% cream that not only halves the traditional concentration of 0.05% without the loss of super-potent (class i) status, but also avoids traditional potency enhancers that are the leading cause of tcs contact allergy, making this an excellent option for those with proven allergies to other tcs, propylene glycol, or sorbitan sesquioleate.33 fixed-dose combination formulations the combination of calcipotriene, a vitamin d analogue, and tcs has previously required either the application of two separate medications or the use of a fixed combination suspension or ointment. as of 2015 and 2020, respectively, both a foam and cream fixed-dose combination therapy of bd 0.064% and calcipotriene 0.005% (cal/bd) are now available. given increased topical therapies skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 572 table 2. new and upcoming topical therapies for psoriasis medication treatment success rates* advantages calcipotriene 0.005% plus betamethasone dipropionate 0.064% aerosol foam 38-54.6% after 4 weeks of daily application48-50 foam vehicle; combined therapy; once-daily application betamethasone dipropionate spray, 0.05% 34.5% after 4 weeks of twice-daily application51 spray vehicle; decreased side effects clobetasol propionate cream, 0.025% 30.1-30.2% after 2 weeks of twicedaily application33 lower steroid concentration than traditional; elimination of allergens halobetasol propionate foam, 0.05% 25.3%-30.7% after 2 weeks of twicedaily application29 foam vehicle halobetasol propionate lotion, 0.01% 37-38% after 8 weeks of daily application31,32 lower steroid concentration than traditional halobetasol propionate 0.01% plus tazarotene 0.045% lotion 35.8%-45.3% after 8 weeks of daily application39 combined therapy; extended application regimens calcipotriene 0.005% plus 37.4% after 8 weeks of daily combined therapy; new less greasy cream formulation; skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 573 betamethasone dipropionate 0.064% cream application52 extended application regimens tapinarof 1% cream† 35.4-40.2% after 12 weeks of daily application44,53 non-steroidal; extended application regimens roflumilast 0.3% cream† 37.5-42.4% after 8 weeks of daily application42 non-steroidal; extended application regimens roflumilast 0.3% foam† ‡ foam vehicle; non-steroidal; extended application regimens *physician’s global assessment of clear or almost clear, with success rate based on phase iii trials only † phase iii trials ongoing, application for regulatory approval pending ‡ phase iii trial data not yet released adapted from buechler et al, 202154 skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 574 bioavailability and enhanced penetration with the foam formulation,34 cal/bd foam provides greater treatment efficacy than cal foam, bd foam, cal/bd gel, and cal/bd ointment.35 a crossover trial showed that half of patients studied strongly preferred cal/bd foam to cal/bd gel as well as their latest topical treatment, particularly if that topical treatment had been an ointment or cream.26 cal/bd cream, meanwhile, relies on a proprietary cream with decreased surfactant and thus improved medication delivery with decreased irritation, and it has outperformed topical suspension in trials.36,37 tazarotene, a vitamin a derivative, can also be used alongside topical steroids to increase efficacy and alleviate safety concerns, although it does carry an independent risk of teratogenicity, photosensitivity, and irritation.38 a fixed-dose lotion of hp 0.01% plus tazarotene 0.045% (hp/taz) approved in 2019 can be used as topical monotherapy for courses of 8 weeks, with greater treatment success than either therapy alone and sustained treatment effect over the ensuing 4 weeks.39 if this extended course of therapy is insufficient, recent data suggest hp/taz lotion can be used daily for up to a year in repeated 4-week intervals on an as-needed basis without adverse events or local skin changes.40 emerging non-steroidal topicals while shortened courses and combination therapy help decrease the risk of tcs side effects, such issues continue to be a longterm concern for many patients, and as such non-corticosteroid topicals have long been a focus of drug development. existing nonsteroidal topical therapies include tazarotene and calcipotriene, as mentioned above, as well as calcineurin inhibitors, coal tar, and keratolytics such as salicylic acid. these therapies can be particularly useful for pediatric applications, intertriginous and sensitive locations, and long-term therapy. however, the stronger anti-inflammatory and antiproliferative effects as well as the easeof-use of tcs has led to the marginalization of these therapies in the clinic. this therapeutic category stands to make a marked resurgence in the coming years with new pde-4 inhibitor and small-molecule topical therapies soon to seek fda approval. both of these novel therapies offer promising efficacy, good local tolerability and the potential for a durable remission. roflumilast, a pde-4 inhibitor, may soon be available in both cream and foam vehicles.41 clinical trials of roflumilast cream show rates of treatment success comparable to available topical treatments with a safety profile that has allowed enrollees as young as two years of age.42 though farther away from regulatory approval, roflumilast foam has shown similar promise, and would pair the safety profile of the pde-4 inhibitor with the popular and easy-to-use foam vehicle.43 tapinarof, a novel, first-in-class, nonsteroidal small-molecule, has shown treatment efficacy at 12 weeks that is similar to that of other topicals,44 as well as further efficacy from continued daily use for up to a year without evidence of tachyphylaxis or any new adverse effects.45 while the advent of biologic therapies has shifted treatment strategy, non-biologic options remain essential for psoriasis care at all stages of severity. currently available and emerging oral, topical, and uv-light based therapies can achieve excellent disease control, in addition to being adjuncts to biologic therapy when appropriate. upcoming advances in therapy with new oral tyk2 inhibitors and non-steroidal conclusion skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 575 topical options will dramatically affect the future treatment paradigm. it is imperative for dermatologists to remain informed about this changing landscape, as shared decision-making with patients regarding desired characteristics, unwanted sideeffects, and level of expected efficacy of treatment modalities can lead to improved satisfaction and disease control. conflict of interest disclosures: dr. buechler and dr. veenstra have nothing to disclose. dr. stein gold reports grants and personal fees from leo pharma, arcutis, abbvie, ucb, bms, amgen, incyte, ortho derm, pfizer, dermavant, and sun. funding: none corresponding author: linda stein gold, md department of dermatology henry ford health system 6530 farmington rd west bloomfield, mi 48322 telephone: 248-661-8764 email: lstein1@hfhs.org references: 1. armstrong aw, read c. 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[press release]. april 23, 2021. skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 576 17. coven tr, burack lh, gilleaudeau p, keogh m, ozawa m, krueger jg. narrowband uv-b produces superior clinical and histopathological resolution of moderate-tosevere psoriasis in patients compared with broadband uv-b2. archives of dermatology. 1997;133(12):1514-1522. 18. zhang p, wu mx. a clinical review of phototherapy for psoriasis. lasers in medical science. 2018;33(1):173-180. 19. weatherhead sc, farr pm, reynolds nj. spectral effects of uv on psoriasis. photochemical & photobiological sciences. 2013;12(1):47-53. 20. stein gold lf. topical therapies for psoriasis: improving management strategies and patient adherence. semin cutan med surg. 2016;35(2 suppl 2):s36-44; quiz s45. 21. armstrong aw, robertson ad, wu j, schupp c, lebwohl mg. undertreatment, treatment trends, and treatment dissatisfaction among patients with psoriasis and psoriatic arthritis 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philipp s. patients with psoriasis have different preferences for topical therapy, highlighting the importance of individualized treatment approaches: randomized phase iiib pso-insightful study. journal of the european academy of dermatology and venereology. 2017;31(11):1876-1883. 27. stein gold l, jackson jm, knuckles ml, weiss js. improvement in extensive moderate plaque psoriasis with a novel emollient spray formulation of betamethasone dipropionate 0.05. j drugs dermatol. 2016;15(3):334-342. 28. fowler jf, jr., hebert aa, sugarman j. dfd01, a novel medium potency betamethasone dipropionate 0.05% emollient spray, demonstrates similar efficacy to augmented betamethasone dipropionate 0.05% lotion for the treatment of moderate plaque psoriasis. j drugs dermatol. 2016;15(2):154162. 29. bhatia n, stein gold l, kircik lh, schreiber r. two multicenter, randomized, doubleblind, parallel group comparison studies of a novel foam formulation of halobetasol propionate, 0.05% vs its vehicle in adult subjects with plaque psoriasis. j drugs dermatol. 2019;18(8):790-796. 30. hebert a, schrieber r, glaab d, eichenfield l. phase iv open label evaluation of the adrenal suppression potential and pharmacokinetic properties of twice daily halobetasol propionate foam, 0.05% in adolescent subjects with plaque psoriasis. skin the journal of cutaneous medicine. 2020;4(6):s77-s77. 31. sugarman jl, weiss js, tanghetti ea, et al. safety and efficacy of halobetasol propionate lotion 0.01% in the treatment of moderate to severe plaque psoriasis: a pooled analysis of 2 phase 3 studies. cutis. 2019;103(2):111116. 32. green lj, kerdel fa, cook-bolden fe, et al. safety and efficacy of a once-daily halobetasol propionate 0.01% lotion in the treatment of moderate-to-severe plaque psoriasis: results of two phase 3 randomized controlled trials. j drugs dermatol. 2018;17(10):1062-1069. 33. del rosso jq. topical corticosteroid therapy for psoriasis-a review of clobetasol propionate 0.025% cream and the clinical relevance of penetration modification. the journal of clinical and aesthetic dermatology. 2020;13(2):22-29. 34. lind m, nielsen kt, schefe lh, et al. supersaturation of calcipotriene and betamethasone dipropionate in a novel aerosol foam formulation for topical treatment of psoriasis provides enhanced bioavailability of the active ingredients. dermatol ther (heidelb). 2016;6(3):413-425. skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 577 35. stein gold l, lebwohl m, menter a, villumsen j, rosen m, koo j. aerosol foam formulation of fixed combination calcipotriene plus betamethasone dipropionate is highly efficacious in patients with psoriasis vulgaris: pooled data from three randomized controlled studies. j drugs dermatol. 2016;15(8):951-957. 36. selmer j vb, præstegaard m, and gold ls. mc2-01 cream has improved overall psoriasis treatment efficacy compared to calcipotriene plus betamethasone dipropionate topical suspension. j psoriasis psoriatic arthritis 2019;4(3):166-167. 37. daniel d, waddell a. compliance with national comprehensive cancer network anti-emesis guidelines in a community hospital cancer center. j oncol pharm pract. 2016;22(1):26-30. 38. gollnick h, menter a. combination therapy with tazarotene plus a topical corticosteroid for the treatment of plaque psoriasis. the british journal of dermatology. 1999;140 suppl 54:18-23. 39. gold ls, lebwohl mg, sugarman jl, et al. safety and efficacy of a fixed combination of halobetasol and tazarotene in the treatment of moderate-to-severe plaque psoriasis: results of 2 phase 3 randomized controlled trials. j am acad dermatol. 2018;79(2):287293. 40. lebwohl mg, sugarman jl, gold ls, et al. long-term safety results from a phase 3 open-label study of a fixed combination halobetasol propionate 0.01% and tazarotene 0.045% lotion in moderate-tosevere plaque psoriasis. j am acad dermatol. 2019;80(1):282-285. 41. li h, zuo j, tang w. phosphodiesterase-4 inhibitors for the treatment of inflammatory diseases. front pharmacol. 2018;9:1048. 42. arcutis announces positive topline results from pivotal dermis-1 and -2 phase 3 trials of topical roflumilast cream (arq-151) in plaque psoriasis. https://www.biospace.com/article/releases/ar cutis-announces-positive-topline-resultsfrom-pivotal-dermis-1-and-2-phase-3-trialsof-topical-roflumilast-cream-arq-151-inplaque-psoriasis/. published 2021. updated february 1. accessed. 43. kircik lh, moore a, bhatia n, et al. oncedaily roflumilast foam 0.3% for scalp and body psoriasis: a randomized, double-blind, vehicle-controlled phase 2b study. american academy of dermatology virtual meeting experience; 2021. 44. gold ls, blauvelt a, armstrong a, et al. tapinarof cream 1% once daily for plaque psoriasis: secondary efficacy outcomes from two pivotal phase 3 trials. american academy of dermatology virtual meeting experience; 2021. 45. dermavant: promising interim analysis from third phase 3 trial for tapinarof in psoriasis. https://practicaldermatology.com/news/derma vant-promising-interim-analysis-from-thirdphase-3-trial-for-tapinarof-in-psoriasis. published 2021. updated february 18. accessed. 46. dogra s, jain a, kanwar aj. efficacy and safety of acitretin in three fixed doses of 25, 35 and 50 mg in adult patients with severe plaque type psoriasis: a randomized, double blind, parallel group, dose ranging study. j eur acad dermatol venereol. 2013;27(3):e305-311. 47. maza a, montaudié h, sbidian e, et al. oral cyclosporin in psoriasis: a systematic review on treatment modalities, risk of kidney toxicity and evidence for use in non-plaque psoriasis. journal of the european academy of dermatology and venereology. 2011;25(s2):19-27. 48. lebwohl m, tyring s, bukhalo m, et al. fixed combination aerosol foam calcipotriene 0.005% (cal) plus betamethasone dipropionate 0.064% (bd) is more efficacious than cal or bd aerosol foam alone for psoriasis vulgaris: a randomized, double-blind, multicenter, three-arm, phase 2 study. j clin aesthet dermatol. 2016;9(2):34-41. 49. koo j, tyring s, werschler wp, et al. superior efficacy of calcipotriene and betamethasone dipropionate aerosol foam versus ointment in patients with psoriasis vulgaris--a randomized phase ii study. j dermatolog treat. 2016;27(2):120-127. 50. paul c, stein gold l, cambazard f, et al. calcipotriol plus betamethasone dipropionate aerosol foam provides superior efficacy vs. gel in patients with psoriasis vulgaris: randomized, controlled pso-able study. j eur acad dermatol venereol. 2017;31(1):119-126. 51. sidgiddi s, pakunlu ri, allenby k. efficacy, safety, and potency of betamethasone dipropionate spray 0.05%: a treatment for adults with mild-to-moderate plaque https://www.biospace.com/article/releases/arcutis-announces-positive-topline-results-from-pivotal-dermis-1-and-2-phase-3-trials-of-topical-roflumilast-cream-arq-151-in-plaque-psoriasis/ https://www.biospace.com/article/releases/arcutis-announces-positive-topline-results-from-pivotal-dermis-1-and-2-phase-3-trials-of-topical-roflumilast-cream-arq-151-in-plaque-psoriasis/ https://www.biospace.com/article/releases/arcutis-announces-positive-topline-results-from-pivotal-dermis-1-and-2-phase-3-trials-of-topical-roflumilast-cream-arq-151-in-plaque-psoriasis/ https://www.biospace.com/article/releases/arcutis-announces-positive-topline-results-from-pivotal-dermis-1-and-2-phase-3-trials-of-topical-roflumilast-cream-arq-151-in-plaque-psoriasis/ https://www.biospace.com/article/releases/arcutis-announces-positive-topline-results-from-pivotal-dermis-1-and-2-phase-3-trials-of-topical-roflumilast-cream-arq-151-in-plaque-psoriasis/ https://practicaldermatology.com/news/dermavant-promising-interim-analysis-from-third-phase-3-trial-for-tapinarof-in-psoriasis https://practicaldermatology.com/news/dermavant-promising-interim-analysis-from-third-phase-3-trial-for-tapinarof-in-psoriasis https://practicaldermatology.com/news/dermavant-promising-interim-analysis-from-third-phase-3-trial-for-tapinarof-in-psoriasis skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 578 psoriasis. j clin aesthet dermatol. 2018;11(4):14-22. 52. stein gold l, green lj, dhawan s, vestbjerg b, praestegaard m, selmer j. a phase 3, randomized trial demonstrating the improved efficacy and patient acceptability of fixed dose calcipotriene and betamethasone dipropionate cream. j drugs dermatol. 2021;20(4):420-425. 53. bissonnette r, strober b, lebwohl m, et al. tapinarof cream 1% once daily for plaque psoriasis: patient-reported outcomes from two pivotal phase 3 trials. american academy of dermatology virtual meeting experience; 2021. 54. buechler cr, veenstra j, stein gold l. new topical therapies for psoriasis. dermatological reviews. 2021. presented at fall clinical dermatology | las vegas, nevada | october 18–21, 2018. previously presented at the 5th world psoriasis and psoriatic arthritis conference 2018 figure 1. did you discuss family planning with your hcp? a comprehensive survey assessing the family planning needs of women with psoriasis m. lebwohl,1 m. siegel,2 l. shankle,2 l. pisenti,3 m. yassine,4 a. s. van voorhees4 1icahn school of medicine at mount sinai, ny; 2national psoriasis foundation, portland, or; 3ucb pharma, smyrna, ga; 4eastern virginia medical school, norfolk, va background • psoriasis (pso) is an immune-mediated inflammatory disease, affecting around 3% of adults in the united states1,2 and 2–6% in europe.3 • the onset, diagnosis and treatment of pso in women often overlaps with their peak reproductive years.4 • family planning is challenging for patients in terms of balancing their own health with the health of their baby. – “…being pregnant completely flared up that would not be fun…. but if i were to have a child, it would be my one shot. i couldn’t see myself doing anything to hurt that one chance...” – patient with pso, focus group conducted by the national psoriasis foundation (npf) • data on patients’ family planning experiences are needed to optimize pso management. methods • we conducted a survey of women of childbearing potential to understand their experiences, concerns and unmet needs with regard to family planning. • eligible patients were aged 18–45, diagnosed with pso (including patients with psoriatic arthritis). • patients were invited to complete a web-based survey on surveygizmo®, disseminated using e-blasts (the npf, advance e-news and talkpsoriasis.org mailing lists) and social media (facebook and twitter). • the survey included questions on patients’ experience, concerns and educational needs, and were informed by the findings of focus groups and interviews of patients and their partners conducted by the npf. • responses to the survey were collected dec 2017–feb 2018. results patients • 141 patients completed the survey: 65% were currently, or in the future would be, trying to conceive, 6% were currently pregnant, and 43% had given birth in the last 5 years (table 1). family planning • figure 1 shows the proportion of patients who discussed family planning with their healthcare providers (hcps). • this family planning discussion was initiated by the pso hcp in just 7.4% of cases (figure 2). • many patients did not inform their hcp of their pregnancy right away, and many did not inform their hcp at all (figure 3). • patients mostly used the internet, the npf and their obstetrician/ gynecologist or midwife for family planning information (table 2). • flare management and the safety of medications during pregnancy were commonly identified by patients as unmet educational needs (table 2). treatment during and after pregnancy • most patients stopped treatment for pso during pregnancy (figure 4). • while many patients who stopped treatment experienced a worsening in the severity of their psoriatic disease (figure 4), only 33% of those who had given birth in the last 5 years had a plan for what to do if they experienced a flare during pregnancy. objective • to evaluate the experience, concerns and family planning needs of women of childbearing potential with psoriasis. figure 2. who initiated the family planning conversation you had with your pso treatment provider? hcp: healthcare provider; ob/gyn: hcp from obstetrics and gynecology; psa: psoriatic arthritis; pso: psoriasis. given birth in the last 5 years (n=61) currently pregnant (n=8) trying to conceive (n=91) age (years), mean 36 34 35 have you ever been diagnosed by a hcp with pso, psa or both?, % respondents pso only 70.5 62.5 18.7 pso and psa 29.5 37.5 81.3 do you currently have..., % respondents no or very little pso 14.8 25.0 2.2 only a few patches (1–2% bsa) 21.3 25.0 11.0 scattered patches (3–4% bsa) 29.5 37.5 64.8 scattered patches (5–10% bsa) 21.3 0 18.7 extensive/very extensive (>10% bsa) 13.1 12.5 3.3 generally, what type of treatment are you on?, % respondents biologics 49.2 25.0 57.8 phototherapy 9.8 12.5 48.2 topical medications 42.6 50.0 47.0 systemic medications 11.5 12.5 43.4 over-the-counter products 34.4 37.5 22.9 bsa: body surface area affected by psoriasis; hcp: healthcare provider; psa: psoriatic arthritis; pso: psoriasis. table 1. disease and treatment characteristics table 2. family planning information and resources used or desired by patients figure 3. how long after you found out you were pregnant did you inform your pso/psa treatment provider? figure 4. stopping treatment for pso/psa while preparing for pregnancy for patients who had given birth in the last 5 years hcp: healthcare provider; ob/gyn: hcp from obstetrics and gynecology; psa: psoriatic arthritis; pso: psoriasis. conclusions • many women of childbearing potential with psoriatic disease take systemic medications. however, many patients delayed or failed to inform their pso/psa hcp of their pregnancy, and family planning discussions were rarely initiated by the hcp. • hcps should prioritize discussing family planning, and plan treatment around/during pregnancy. • the unmet educational needs of women of childbearing potential with pso/psa included the impact of treatment on their baby, and flare management during pregnancy. • the relatively few respondents who were currently pregnant made capturing their experiences difficult. the hcp treating my pso and/or psa: 7.4% i did: 50.0% my partner did: 41.0% my ob/gyn or midwife: 1.6% 3% trying to conceive (n=91)currently pregnant (n=8) given birth in the last 5 years (n=61) 0 908070605040302010 100 no, i did not discuss family planning with my hcp no, my pregnancy was unplanned yes, with my dermatologist and/or rheumatologist yes, with my ob/gyn and/or midwife proportion of patients (%) 79% 25% 25% 25% 25% 1% 13% 8% 67% 53% 30% within 1 month right away within 3 months within 6 months i did not discuss my pregnancy other currently pregnant (n=8) 0 908070605040302010 100 given birth in the last 5 years (n=61) proportion of patients (%) 25% 25% 37.5% 12.5% 42.6% 13.1% 16.4% 3.3% 19.7% 4.9% 0 908070605040302010 100 proportion of patients (%)what did you decide to do regarding treatment for your psoriasis and/or psoriatic arthritis during pregnancy? (n=61) what happened to the severity of your psoriasis? did you and your hcp talk about when you would restart? if you stopped treatment (n=40): why did you stop treatment? stop treatment 66% change/stay on treatment 30% i was worried about treatment harming the fetus 78% i was worried about the negative side e�ects of the treatment on my fertility 38% lack of information regarding treatment compatibility with pregnancy 33% worsened 43% stayed the same 33% improved 25% yes: dermatologist/rheumatologist 60% yes: ob/gyn or midwife 28% no 30% immediately post-partum 22% 17%within 4 weeks of childbirth 26%within 6 months of childbirth when were you advised to restart?if yes (n=23): upon experiencing post-partum flare 22% summary women of childbearing potential with psoriatic disease were surveyed to assess their family planning needs. of patients delayed informing their pso/psa treatment provider of their pregnancy. 20% did not tell them at all of conversations were initiated by the hcp of patients trying to conceive were taking systemic medications 43% 33% 7% of patients discussed family planning with their pso/psa treatment provider, but only 68% of mothers stopping treatment during pregnancy are advised to wait until they experienced a post-partum flare before restarting treatment 22% these results show that healthcare providers should prioritize family planning discussions and tailor treatment plans to the needs of women of childbearing potential. hcp: healthcare provider; ob/gyn: hcp from obstetrics and gynecology. references: 1. rachakonda et al. j am acad dermatol. 2014;70:512–6; 2. kurd et al. j am acad dermatol. 2009;60:218–24; 3. danielsen et al. br j dermatol. 2013;168:1303–10; 4. farber et al. dermatologica. 1974;148:1–18. author contributions: substantial contributions to study conception/ design, or acquisition/analysis/interpretation of data: ml, ms, ls, lp, my, asvv; drafting of the publication, or revising it critically for important intellectual content: ml, ms, ls, lp, my, asvv; final approval of the publication: ml, ms, ls, lp, my, asvv. author disclosures: ml: employee of mount sinai which receives research funds from: abbvie, amgen, boehringer ingelheim, celgene, eli lilly, janssen/johnson & johnson, kadmon, medimmune/astra zeneca, novartis, pfizer, valeant and vidac. also a consultant for allergan, aqua leo-pharma, and promius. ms, ls: employee of national psoriasis foundation. the national psoriasis foundation receives unrestricted financial support from abbvie, amgen, boehringer ingleheim, celgene, dermira, lilly, janssen biotech, novartis, ortho dermatologics, pfizer, sandoz, strata, taro and ucb. lp, my: employees of ucb pharma. asvv: consultant for: dermira, novartis, celgene, abbvie; board member of dermira, novartis, celgene, abbvie, allergan, derm tech, valeant, webmd; ex-spouse pension: merck. acknowledgements: this study was funded by ucb pharma. the survey was conducted by the national psoriasis foundation. we thank the patients who contributed to this study. the authors acknowledge lisa pisenti, pharmd, ucb pharma, georgia usa, for publication coordination, and hinal tanna, phd, costello medical, cambridge uk, for medical writing and editorial assistance. all costs associated with development of this poster were funded by ucb pharma. given birth in the last 5 years (n=61) currently pregnant (n=8) trying to conceive (n=91) while preparing for pregnancy, where do you/did you get your information about family planning as it relates to your psoriasis and/or psoriatic arthritis?, % respondents online source (i.e. webmd) 45.9 12.5 80.2 national psoriasis foundation 42.6 50.0 78.0 internet forums/ chat rooms 34.4 50.0 49.5 ob/gyn or midwife 36.1 25.0 52.7 hcp for psoriatic disease 55.7 25.0 28.6 family and/or friends 6.6 25.0 37.4 what type(s) of additional information do you/did you want related to family planning and psoriasis and/or psoriatic arthritis?, % respondents how to manage a flare during pregnancy 60.7 62.5 62.6 safety of medications during pregnancy 77.0 50.0 38.5 how the disease could affect the developing fetus 41.0 62.5 64.8 how disease is genetically passed/relative risk 57.4 25.0 51.6 what other resources would be most helpful to you related to psoriatic disease and family planning?, % respondents internet resources that specifically address pregnancy and psoriatic disease 71.7 62.5 47.2 lactation resources 43.3 50.0 65.2 mental health resources 38.3 37.5 39.3 patient support groups 35.0 37.5 53.9 the 3 most selected answers for each question by each subgroup are highlighted in bold. hcp: healthcare provider; ob/gyn: hcp from obstetrics and gynecology. skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 453 in-depth review vascular effects of pseudoxanthoma elasticum erika l. hubbard, ba1, mark g. lebwohl, md1 1the kimberly and eric j. waldman department of dermatology, icahn school of medicine at mount sinai hospital, new york, ny pseudoxanthoma elasticum (pxe) is a rare autosomal recessive disease caused by biallelic mutation of the abcc6 gene. the condition is characterized by the degradation and calcification of elastic fibers in connective tissue, including the skin, eyes, and arterial media, resulting in cutaneous yellowish papules, angioid streaks in bruch’s membrane, and vascular calcification. prevalence of the condition is estimated from 1:25,000 to 1:56,000, with a 2:1 female to male ratio. 1,2 the vascular effects of pxe are extensive. the abcc6 gene maintains inorganic phosphate levels that inhibit calcification, so it follows that loss of abcc6 function results in systemic calcification.3 arterial calcification caused by elastin degradation is associated with increased carotid intimamedia thickness, which puts pxe patients at higher risk of developing cardiovascular and cerebrovascular disease.4 some studies suggest that older pxe patients also have increased arterial compressibility and distensibility, though debate on this issue remains.5-7 in this paper, we reviewed the abstract background: pseudoxanthoma elasticum (pxe) is a rare hereditary disease caused by mutations in the abcc6 gene, characterized by ectopic calcification of connective tissue throughout the body. vascular conditions associated with pxe have been well-documented in the literature, but to our knowledge, analysis of the myriad of pxe case reports with associated vascular diseases in addition to larger cohort studies, has not been undertaken. methods: a search of the pubmed database using the key words “pseudoxanthoma elasticum” and “vascular” was performed. results: a total of 345 cases of pvd, 97 cases of cvd, and 123 case of cevd were reported. additionally, 88 cases of hypertension and 5 cases of crm were reported. conclusions: pxe patients are at risk of developing serious vascular conditions, particularly peripheral vascular disease. this condition also appears to have some connection to carotid rete mirabile, which is extremely rare in humans. further research should be conducted to analyze the connection between pxe and crm in order to better understand and treat both conditions. introduction skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 454 literature published on vascular conditions associated with pxe, broadly categorized as peripheral vascular disease, cardiovascular disease, cerebrovascular disease, hypertension, and carotid rete mirabile, in order to capture a general idea of the prevalence and range of this association. we performed a pubmed search using the terms “pseudoxanthoma elasticum” and “vascular,” and limited our analysis to english-language, french-language studies, and studies with abstracts in english with extractable data. animal studies, treatment studies, and pxe studies focusing on cutaneous or ophthalmologic symptoms were excluded. articles without full-text availability were also excluded from our review. of the 90 relevant articles, upon review of the case descriptions, 73 had extractable vascular conditions data to analyze, comprised of 59 case studies/series and 14 cohort/cross-sectional studies. from the 73 relevant articles, 1049 pxe patients were reported. of these patients, 345 had some form of peripheral vascular disease (pvd), 97 had cardiovascular disease, and 123 had cerebrovascular disease. the most common pvd diagnoses included intermittent claudication (24 patients), lower limb atherosclerosis (67 patients), and peripheral arterial stenosis or occlusion (23 patients). cardiovascular table 1. characteristics of included cohort and crosssectional studies reference patients pvd cvd cevd ht crm campens et al.8 32 13 0 10 8 0 gutierrezcardo et al.9 18 5 2 1 6 0 hammami et al.10 22 0 0 0 0 0 iwanaga et al.11 76 24 18 0 0 0 kauw et al.12 178 0 0 29 0 0 leftheriotis et al.13 71 40 7 8 18 0 legrand et al.14 194 84 37 17 0 0 nollet et al.15 56 18 6 17 17 0 omarjee et al.16 151 0 0 13 0 0 omarjee et al.17 23 9 1 1 0 0 passon et al.18 44 44 0 0 0 0 pingel et al.19 46 45 0 0 0 0 utani et al.20 14 0 4 0 0 0 vanakker et al.21 38 22 7 6 17 0 totals 963 304 82 102 66 0 pvd: peripheral vascular disease; cvd: cardiovascular disease; cevd: cerebrovascular disease; ht: hypertension; crm: carotid rete mirabile disease conditions primarily consisted of myocardial infarction (15 patients), angina pectoris (12 patients), and coronary artery disease (7 patients). transient ischemic attacks (17 patients), ischemic strokes (67 patients), and carotid artery disease or stenosis (31 patients) accounted for the bulk of cerebrovascular disease cases. it is also worth noting that 88 pxe patients had hypertension. additionally, 5 case study patients presented with carotid rete mirabile, a rare disorder characterized by an arterial methods results skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 455 network communicating between the internal and external carotid networks. from our pubmed search, it appears that peripheral vascular, cardiovascular, and cerebrovascular disease are all welldocumented among pxe patients in the literature. these comorbidities are expected considering the arterial calcification of elastic tissue that occurs as a result of abcc6 mutations. arterial calcification alters the elastic properties of the arterial wall, causing it to stiffen, which consequently increases systemic arterial pressure.2 peripheral vascular disease (pvd), detected by low ankle-brachial index (abi), absence of ankle pulse, and lower limb claudication, is particularly well-documented in patients with pxe (45% of french pxe cohort, 53% of belgian pxe cohort).21,81 cardiovascular abnormalities, including angina pectoris and myocardial infarction, are relatively rare (15% with angina pectoris and 5% myocardial infarction in large cohort study).21 cerebrovascular events are also relatively rare, but occur at significantly higher rates in pxe patients relative to the general population (around 8% prevalence of cerebrovascular accidents in pxe patients, compared to 3% prevalence in general population).82 hypertension is quite common among pxe patients (25% in leftheriotis et al. 2014; 41% in vanakker et al.).13,21 though hypertension has historically been viewed as a risk factor in developing arterial calcification, more recent research has found that arterial calcification also causes hypertension in the elderly, suggesting that arterial calcification and hypertension are part of a vicious cycle of vascular aging.83 this relationship has particular relevance to pxe patients, whose vascular condition can be characterized as early-onset vascular aging.51 reports of five pxe patients with carotid rete mirabile (crm) is particularly intriguing. a rete mirabile is a vascular network of arteries and arterioles that replaces the normal adult carotid arteries. crm supplies the brain in lower mammals, but is absent in normal human development.84 individuals with crm most commonly present clinically with hemorrhagic or ischemic strokes. this and other cerebrovascular malformations have generally been treated as only coincidentally associated with pxe. however, of the 32 human cases of crm reported in the literature before 2011, five (16%) were pxe patients.75 given that both crm and pxe are quite rare conditions, it seems unlikely that they would accidentally co-occur at this frequency. some researchers have suggested that abnormal signaling caused by abcc6 mutation during embryological development could create abnormalities in arterial wall construction, including crm, implying a systematic association between pxe and crm.75 in conclusion, pxe patients often suffer from a wide range of vascular conditions, most common of which is peripheral vascular disease. hypertension is also quite prevalent among pxe patients, which is of particular concern, as hypertension is not only an effect of pxe, but also a cause of further arterial calcification. a finding of particular interest from this review is the potential systematic association between pxe and crm. further research should be conducted to discern the nature of the relationship, if any, between pxe and crm, as an understanding of a vascular discussion conclusion skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 456 developmental disorder such as crm would further our understanding of pxe and its mechanisms of arterial onset. table 2. characteristics of included case studies/series reference patients pvd cvd cevd ht crm aissaoui et al.22 5 0 0 0 1 0 ammi et al.23 4 4 0 0 0 0 araki et al.24 1 1 1 1 1 0 araki et al.25 1 0 0 1 0 1 bardsley et al.26 2 2 0 0 1 0 barrie et al.27 2 1 0 1 1 0 bete et al.28 1 0 1 0 0 0 bock et al.29 1 0 0 1 0 0 bruno et al.30 4 0 1 2 4 0 cailleux et al.31 1 1 0 0 0 0 carter et al.32 1 1 0 0 0 0 chalk et al.33 1 0 0 1 0 0 dalloz et al.34 1 0 0 1 0 0 del zotto et al.35 1 0 0 1 0 1 devriese et al.36 1 1 0 0 0 0 dibi et al.37 4 0 1 0 4 0 dymock et al.38 1 1 1 0 1 0 ekim et al.39 1 0 0 0 1 0 elhatimi et al.40 1 0 0 0 1 0 fasshauer et al.41 1 0 0 1 0 0 galle et al.42 1 0 0 1 0 0 garcía acuña et al.43 1 0 1 0 0 0 gillgren et al.44 1 1 0 0 0 0 heno et al.45 1 0 1 0 0 0 jackson et al.46 1 1 0 0 0 0 kévorkian et al.47 1 0 1 0 0 0 khan et al.48 1 1 0 0 0 0 lamb et al.49 1 1 0 0 0 0 li et al.50 1 0 0 0 0 0 mendelsohn et al.51 3 3 0 0 1 0 miki et al.52 1 0 0 0 0 0 miwa et al.53 1 0 0 0 1 0 skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 457 montani et al.54 1 1 1 0 0 0 neumann et al.55 1 1 0 0 0 0 nishida et al.56 1 0 1 0 0 0 nolte et al.57 1 0 1 0 0 0 pavlovic et al.58 3 0 0 3 2 0 perdu et al.59 7 7 0 0 0 0 pieczuro et al.60 1 0 0 1 0 0 rios-montenegro et al.61 1 0 0 0 0 1 rodríguez-camarero et al.62 1 1 0 0 0 0 rühlmann et al.63 1 1 0 0 0 0 sabán-ruiz et al.64 1 0 0 0 1 0 sasai et al.65 1 1 0 0 0 0 schröder et al.66 1 1 0 1 0 0 sharma et al.67 1 0 0 1 1 0 siskos et al.68 1 1 0 0 0 0 slade et al.69 1 1 0 0 0 0 song et al.70 1 1 2 0 0 0 sunmonu et al.71 1 0 0 1 0 0 takeshita et al.72 1 0 0 1 0 0 tromp et al.73 2 1 0 0 0 0 ul bari et al.74 1 1 0 0 1 0 vasseur et al.75 1 0 1 0 0 1 wahlqvist et al.76 2 2 0 0 0 0 wolff et al.77 1 1 0 0 0 0 yasuhara et al.78 1 0 1 1 0 1 zimmo et al.79 1 0 0 0 0 0 zuily et al.80 1 1 0 1 0 0 totals 86 41 15 21 22 5 pvd: peripheral vascular disease; cvd: cardiovascular disease; cevd: cerebrovascular disease; ht: hypertension; crm: carotid rete mirabile conflict of interest disclosures: none funding: none corresponding author: erika hubbard 95 w 95th street, 16th floor, new york, ny 10025 phone: (435)890-5272 email: elh2174@columbia.edu references: 1. kranenburg g, baas af, de jong pa, et al. the prevalence of pseudoxanthoma elasticum: revised estimations based on genotyping in a high vascular risk cohort. eur j med genet. feb 2019;62(2):90-92. 2. leftheriotis g, omarjee l, le saux o, et al. the vascular phenotype in pseudoxanthoma elasticum and related disorders: contribution of a mailto:elh2174@columbia.edu skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 458 genetic disease to the understanding of vascular calcification. front genet. 2013;4:4. 3. bartstra jw, spiering w, van den ouweland jmw, mali w, janssen r, de jong pa. increased elastin degradation in pseudoxanthoma elasticum is associated with peripheral arterial disease independent of calcification. j clin med. aug 26 2020;9(9). 4. kranenburg g, visseren flj, de borst gj, de jong pa, spiering w, studygroup s. arterial stiffening and thickening in patients with pseudoxanthoma elasticum. atherosclerosis. mar 2018;270:160-165. 5. kornet l, bergen aa, hoeks ap, et al. in patients with pseudoxanthoma elasticum a thicker and more elastic carotid artery is associated with elastin fragmentation and proteoglycans accumulation. ultrasound med biol. aug 2004;30(8):1041-1048. 6. boutouyrie p, germain dp, tropeano a, et al. compressibility of the carotid artery in patients with pseudoxanthoma elasticum. hypertension. 2001;38(5):1181-1184. 7. germain dp, boutouyrie p, laloux b, laurent s. arterial remodeling and stiffness in patients with pseudoxanthoma elasticum. arterioscler thromb vasc biol. may 1 2003;23(5):836-841. 8. campens l, vanakker om, trachet b, et al. characterization of cardiovascular involvement in pseudoxanthoma elasticum families. arterioscler thromb vasc biol. nov 2013;33(11):2646-2652. 9. gutierrez-cardo a, lillo e, murcia-casas b, et al. skin and arterial wall deposits of 18f-naf and severity of disease in patients with pseudoxanthoma elasticum. j clin med. may 8 2020;9(5). 10. hammami h, badri t, benmously r, et al. pseudoxanthoma elasticum: a study of 22 cases. rev med liege. 2009;64(12):629. iwanaga a, okubo y, yozaki m, et al. analysis of clinical symptoms and abcc6 mutations in 76 japanese patients with pseudoxanthoma elasticum. j dermatol. jun 2017;44(6):644-650. 11. kauw f, kranenburg g, kappelle lj, et al. cerebral disease in a nationwide dutch pseudoxanthoma elasticum cohort with a systematic review of the literature. j neurol sci. feb 15 2017;373:167-172. 12. leftheriotis g, kauffenstein g, hamel jf, et al. the contribution of arterial calcification to peripheral arterial disease in pseudoxanthoma elasticum. plos one. 2014;9(5):e96003. 13. legrand a, cornez l, samkari w, et al. mutation spectrum in the abcc6 gene and genotypephenotype correlations in a french cohort with pseudoxanthoma elasticum. genet med. aug 2017;19(8):909-917. 14. nollet l, campens l, de zaeytijd j, et al. clinical and subclinical findings in heterozygous abcc6 carriers: results from a belgian cohort and clinical practice guidelines. j med genet. apr 5 2021. 15. omarjee l, fortrat jo, larralde a, et al. internal carotid artery hypoplasia: a new clinical feature in pseudoxanthoma elasticum. j stroke. jan 2019;21(1):108-111. 16. omarjee l, mention pj, janin a, et al. assessment of inflammation and calcification in pseudoxanthoma elasticum arteries and skin with 18f-flurodeoxyglucose and 18f-sodium fluoride positron emission tomography/computed tomography imaging: the gocapxe trial. j clin med. oct 27 2020;9(11). 17. passon sg, kullmar v, blatzheim ak, et al. carotid strain measurement in patients with pseudoxanthoma elasticum hint for a different pathomechanism? intractable rare dis res. feb 2018;7(1):25-31. 18. pingel s, pausewang ks, passon sg, et al. increased vascular occlusion in patients with pseudoxanthoma elasticum. vasa-european journal of vascular medicine. 2017;46(1):47-52. 19. utani a, tanioka m, yamamoto y, et al. relationship between the distribution of pseudoxanthoma elasticum skin and mucous membrane lesions and cardiovascular involvement. j dermatol. feb 2010;37(2):130136. 20. vanakker om, leroy bp, coucke p, et al. novel clinico-molecular insights in pseudoxanthoma elasticum provide an efficient molecular screening method and a comprehensive diagnostic flowchart. hum mutat. jan 2008;29(1):205. 21. aissaoui r, derbel f, jallouli a, et al. 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[early pseudoxanthoma elasticum with severe cardiovascular involvement]. ann dermatol venereol. mar 2004;131(3):275-278. 27. bete jm, banas js, jr., moran j, pinn v, levine hj. coronary artery disease in an 18 year old with pseudoxanthoma elasticum: successful surgical therapy. am j cardiol. oct 6 1975;36(4):515-520. 28. bock a, schwegler g. intracerebral haemorrhage as first manifestation of pseudoxanthoma elasticum. clin neurol neurosurg. mar 2008;110(3):262-264. 29. bruno g, ritelli m, di pietro a, et al. clinical and genetic heterogeneity in a large family with pseudoxanthoma elasticum: mthfr and serpine1 variants as possible disease modifiers in developing ischemic stroke. j stroke cerebrovasc dis. apr 1 2021;30(6):105744. 30. cailleux n, hachulla e, perez-cousin m, labalette p, lecomte-houcke m. [pseudoxanthoma elasticum: a rare cause of leg artery diseases in young adults]. j mal vasc. mar 1997;22(1):51-55. 31. carter dj, woodward da, vince fp. arterial surgery in pseudoxanthoma elasticum. postgrad med j. may 1976;52(607):291-292. 32. chalk jb, patterson mc, pender mp. an intracranial arteriovenous malformation and palatal myoclonus related to pseudoxanthoma elasticum. aust n z j med. apr 1989;19(2):141143. 33. dalloz ma, debs r, bensa c, alamowitch s. [white matter lesions leading to the diagnosis of pseudoxanthoma elasticum]. rev neurol (paris). oct 2010;166(10):844-848. 34. del zotto e, ritelli m, pezzini a, et al. clinical, neuroradiological and molecular features of a patient affected by pseudoxhantoma elasticum associated to carotid rete mirabile: case report. clin neurol neurosurg. jul 2012;114(6):758-761. 35. devriese m, legrand a, courtois m, jeunemaitre x, albuisson j. pseudoxanthoma elasticum with prominent arterial calcifications evoking cd73 deficiency. vasc. med. 2019;24(5):461-464. 36. dibi a, mouane n, el fahime e, dafiri r, bentahila a. calcifications vasculaires dans le pseudoxanthome élastique chez l’enfant. jmv. 2017;42(6):333-337. 37. dymock rb. pseudoxanthoma elasticum: report of a case with reno-vascular hypertension. aust. j. derm. 1979;20(82). 38. ekim m, tümer n, atmaca l, et al. pseudoxanthoma elasticum: a rare cause of hypertension in children. pediatr nephrol. apr 1998;12(3):183-185. 39. elhatimi a, elbakkal a, iguermia s, meziane m, mikou o, mernissi fz. yellow papules: the iceberg of systemic elastorrhexis. pan afr med j. 2013;14:106. 40. fasshauer k, reimers cd, gnau hj, strempel i, rossberg c. neurological complications of grönblad-strandberg syndrome. j neurol. 1984;231(5):250-252. 41. galle g, galle k, huk w, taghavy a. [stenoses of the cerebral arteries in pseudoxanthoma elasticum (author's transl)]. arch psychiatr nervenkr (1970). 1981;231(1):61-70. 42. garcía acuña jm, vázquez caamaño m, gonzález cid a, gonzález-juanatey jr, lópez lago am, gil de la peña m. [coronary ischemia caused by pseudoxanthoma elasticum and myocardial revascularization with double arterial graft]. rev esp cardiol. jul 2001;54(7):908-911. 43. gillgren p, malmstedt j. pseudoxanthoma elasticum and isolated iliac artery occlusion. eur j vasc endovasc surg. sep 2020;60(3):409. 44. heno p, fourcade l, duc hn, et al. [aortocoronary dysplasia and pseudoxanthoma elastica]. arch mal coeur vaiss. apr 1998;91(4):415-418. 45. jackson a, loh cl. pulmonary calcification and elastic tissue damage in pseudoxanthoma elasticum. histopathology. nov 1980;4(6):607611. 46. 47. kévorkian jp, masquet c, kural-ménasché s, le dref o, beaufils p. new report of severe coronary artery disease in an eighteen-year-old girl with pseudoxanthoma elasticum. case report and review of the literature. angiology. aug 1997;48(8):735-741. 47. khan ma, beard j. peripheral vascular disease in an individual with pseudoxanthoma elasticum. eur j vasc endovasc surg. nov 2007;34(5):590591. 48. lamb cm, johns ra, gallagher pj, odurny a, shearman cp. a case of pseudo-xanthoma elasticum presenting with ischaemic claudication. eur j vasc endovasc surg. apr 2012;43(4):478479. 49. li q, baker j, kowalczyk j, jiang q, uitto j, schachner l. paediatric pseudoxanthoma elasticum with cardiovascular involvement. br j dermatol. nov 2013;169(5):1148-1151. skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 460 50. mendelsohn g, bulkley bh, hutchins gm. cardiovascular manifestations of pseudoxanthoma elasticum. arch pathol lab med. jun 1978;102(6):298-302. 51. miki k, yuri t, takeda n, takehana k, iwasaka t, tsubura a. an autopsy case of pseudoxanthoma elasticum: histochemical characteristics. med mol morphol. sep 2007;40(3):172-177. 52. miwa k, higashikata t, mabuchi h. intravascular ultrasound findings of coronary wall morphology in a patient with pseudoxanthoma elasticum. heart. oct 2004;90(10):e61. 53. montani d, jais x, humbert m, sitbon o. pulmonary hypertension complicating pulmonary artery involvement in pseudoxanthoma elasticum. am j respir crit care med. sep 1 2020;202(5):e90-e91. 54. neumann e, mühlberg h. [blood circulation disturbances of the upper extremities as a principle symptom of pseudoxanthoma elasticum]. z gesamte inn med. nov 15 1976;31(22):948-952. 55. nishida h, endo m, koyanagi h, ichihara t, takao a, maruyama m. coronary artery bypass in a 15-year-old girl with pseudoxanthoma elasticum. ann thorac surg. mar 1990;49(3):483-485. 56. nolte kb. sudden cardiac death owing to pseudoxanthoma elasticum: a case report. hum pathol. aug 2000;31(8):1002-1004. 57. pavlovic am, zidverc-trajkovic j, milovic mm, et al. cerebral small vessel disease in pseudoxanthoma elasticum: three cases. can j neurol sci. feb 2005;32(1):115-118. 58. perdu j, champion k, emmerich j, fiessinger jn. [microvascular involvement in pseudoxanthoma elasticum. capillaroscopic findings]. presse med. apr 24 2004;33(8):518521. 59. pieczuro a, lozza m. [cerebrovascular disease and pseudoxanthoma elasticum: apropos of a case]. riv neurol. sep-oct 1981;51(5):261-273. 60. rios-montenegro en, behrens mm, hoyt wf. pseudoxanthoma elasticum. association with bilateral carotid rete mirabile and unilateral carotid-cavernous sinus fistula. arch neurol. feb 1972;26(2):151-155. 61. rodríguez-camarero sj, manchado p, gonzález ja, castro ma, rodero ji, mateo am. [acute arterial thrombosis of the extremity in pseudoxanthoma elasticum]. angiologia. mar-apr 1992;44(2):58-61. 62. rühlmann c, wittig i, lochner a, et al. [grönblad-strandberg syndrome from the angiological viewpoint]. dtsch med wochenschr. mar 13 1998;123(11):312-317. 63. sabán-ruiz j, fabregate fuente r, sánchezlargo uceda e, fabregate fuente m. pseudoxanthoma elasticum: case report with arterial stiffness evaluated by a research cardiovascular profiling system. eur j dermatol. nov-dec 2010;20(6):785-787. 64. sasai h, sakakura k, wada h, sugawara y, ako j, momomura s. stiff coronary stenosis in a young female with pseudoxanthoma elasticum. jacc cardiovasc interv. jan 2012;5(1):112-113. 65. schröder f, hausser i, szliska c, lawall h, diehm c. images in vascular medicine. pseudoxanthoma elasticum: under-recognized cause of early onset peripheral arterial disease? vasc med. nov 2006;11(4):266-267. 66. sharma ng, ghosh sk, beohar pc, gupta ps. subarachnoid haemorrhage in pseudoxanthoma elasticum. postgrad med j. dec 1974;50(590):774-776. 67. siskos d, giannakakis s, makris s, pirgakis k, psyllas a, maltezos c. case report of a patient with iliac occlusive disease due to pseudoxantoma elasticum and review of the bibliography. ann vasc surg. feb 2012;26(2):278.e211-274. 68. slade akb, john rm, swantong rh. pseudoxanthoma elasticum presenting with myocardial infarction. br heart j. 1990;63:372373. 69. song hk, sharoni e, williams b, jr., guyton ra, puskas jd. long-term left internal mammary artery graft patency for coronary artery disease associated with pseudoxanthoma elasticum. ann thorac surg. aug 2004;78(2):691-693. 70. sunmonu na. multiple cerebrovascular insults in pseudoxanthoma elasticum. j stroke cerebrovasc dis. mar 2021;30(3):105524. 71. 72. takeshita t, ozaki m. central retinal artery occlusion in a patient with pseudoxanthoma elasticum. hiroshima j med sci. jun 2003;52(2):33-34. 72. tromp tr, kranenburg g, ossewaarde-van norel j, spiering w. [pseudoxanthoma elasticum: a disorder with different manifestations]. ned tijdschr geneeskd. 2016;160:d203. 73. ul bari a, mehmood t. pseudoxanthoma elasticum. j coll physicians surg pak. oct 2005;15(10):650-652. 74. vasseur m, carsin-nicol b, ebran jm, et al. carotid rete mirabile and pseudoxanthoma elasticum: an accidental association? eur j vasc endovasc surg. sep 2011;42(3):292-294. skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 461 75. wahlqvist ml, fox rm, beech am, favilla i. peripheral vascular disease as a mode of presentation of pseudoxanthoma elasticum. aust n z j med. oct 1977;7(5):523-525. 76. wolff hh, stokes jf, schlesinger be. vascular abnormalities associated with pseudoxanthoma elasticum. arch dis child. feb 1952;27(131):8288. 77. yasuhara t, sugiu k, kakishita m, date i. pseudoxanthoma elasticum with carotid rete mirabile. clin neurol neurosurg. mar 2004;106(2):114-117. 78. zimmo l, rudarakanchana n, thompson m, hamady ms, cheshire nj, bicknell cd. renal artery aneurysm formation secondary to pseudoxanthoma elasticum. j vasc surg. mar 2013;57(3):842-844. 79. zuily s, angioi k, fauret al, et al. severe and diffuse arterial lesions in a patient with pseudoxanthoma elasticum. j am coll cardiol. may 29 2012;59(22):1991. 80. leftheriotis g, abraham p, le corre y, et al. relationship between ankle brachial index and arterial remodeling in pseudoxanthoma elasticum. j vasc surg. nov 2011;54(5):13901394. 81. domzalski c, wei n, lebwohl m. systematic review of neurovascular complications in patients with pseudoxanthoma elasticum. j of skin. 2020;4(6):491-496. 82. kalra ss, shanahan cm. vascular calcification and hypertension: cause and effect. ann med. jun 2012;44 suppl 1:s85-92. 83. mondel pk, saraf r, limaye us. rete mirabile associated with pial arteriovenous fistula: imaging features with literature review. bmj case rep. feb 16 2017;2017. skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 427 brief articles bilateral porokeratosis ptychotropica on the gluteal cleft: a case report and review of the literature roya s. nazarian ba,1 nikki vyas md,1 noah s. scheinfeld md,2 robert g. phelps md1 1department of dermatology, icahn school of medicine at mount sinai, new york, ny 2department of dermatology, mount sinai beth israel, new york, ny porokeratosis comprises a heterogeneous group of disorders of epidermal keratinization. though the exact etiology is unknown, it is likely due to aberrant terminal differentiation of keratinocytes.1 porokeratosis is histologically characterized by the presence of parakeratotic cells within central grooves of the epidermis, called cornoid lamellae. ultraviolet exposure and immune suppression have been reported as triggers that worsen symptoms and can further promote subsequent development of malignant transformation in these lesions. numerous subsets of porokeratosis have been described based on clinical and abstract porokeratosis ptychotropica (pp) is a rare variant of porokoretosis that is distinctive based on its clinical presentation of pruritic, verrucous papules and plaques that often form a “butterfly” shape, commonly located on the perinatal cleft with extension to the buttocks. similar to other variants of porokeratosis, it is histologically distinguished by the presence of cornoid lamellae. proper diagnosis is necessary as some studies suggest that pp may predispose to squamous cell carcinoma. furthermore, there are limited evidence-based treatment options. we report the case of a 47 year-old-male who presented with a rash on the buttocks and legs for 3 years. physical exam revealed erythematous, annular, and verrucous plaques on the bilateral periglueteal area and bilateral distal lower extremities. the patient felt that lesions on the legs were disfiguring but otherwise asymptomatic. biopsy results demonstrated hyperkeratosis and parakeratosis suggestive of cornoid lamellae. clinical and histologic findings were suggestive of pp. lesions on the legs were treated with cryotherapy, which resulted in resolution at a 3-month follow-up. pp remains a diagnostic and therapeutic challenge due to its rarity. no standard of care has been established, though topical calcipotriol, topical imiquimod, topical tretonoin, and cryotherapy have been used with success in the literature. this case highlights unique characteristics of pp in order to aid in early detection and cancer prevention while also describing various treatment modalities. introduction skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 428 histological features, including classic porokeratosis of mibelli, disseminated superficial (actinic) porokeratosis, porokeratosis palmaris et plantaris disseminata, linear porokeratosis and punctate porokeratosis. however, newly described histologic subsets are emerging.2,3 porokeratosis ptychotropica (pp) is a rare variant of porokeratosis, that is distinctive based on its clinical presentation of pruritic, verrucous papules and plaques located most commonly in the perinatal cleft with extension to the buttocks. it was first described in 1995 by lucker et al, who emphasized this variant’s unique predilection for flexural surfaces.4 since then, 20 cases have been individually reported. pp is often a diagnostic challenge, as it is a newly described entity and can be misdiagnosed as psoriasis, dermatophyte infection, condyloma acuminatum, or lichen sclerosis.5 controversy persists regarding both accurate diagnosis and the most effective therapeutic modalities. here, we report a case of porokeratosis ptychotropica and a review of treatment options aimed at improving quality of life. a 47-year-old-male presented with a rash on the buttocks and legs for 3 years. physical exam revealed erythematous, annular, and verrucous plaques on the bilateral periglueteal area and bilateral distal lower extremities (figure 1). lesions on the legs were disfiguring and occasionally painful. a skin biopsy was performed. histopathological examination showed acanthotic epidermis with columns of parakeratosis. no lymphocytic infiltrate or amyloid deposition was noted (figure 2a2b). the clinical and pathological findings were most consistent with a diagnosis of pp. disfiguring and painful lesions on the legs were initially treated with phototherapy without success and subsequently treated with cryotherapy, which resulted in resolution of pain and a satisfactory cosmetic outcome at a 3-month follow-up. figure 1. original clinical presentation of erythematous plaque located on the bilateral gluteal region. figure 2a. original magnification of specimen from gluteal cleft with haematoxylin/eosin stain. case report skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 429 figure 2b. on higher power, there is an acanthotic epidermis within the stratum corneum, with columns of parakeratosis. the correct diagnosis of pp can be challenging. the differential diagnosis includes psoriasis, dermatophyte infection, and lichen sclerosis. yet, pp can clinically be differentiated by the characteristic formation of a butterfly-shaped scaly plaque most often located on the buttocks surrounding the anus. furthermore, the course of symptom development can aid in diagnosis, as this disease has an indolent course with slow growth generally over 5-10 years.6 epidemiologic evidence suggests that porokeratosis presents on average in the 5th decade of life with ~90% of cases occurring in males.6 histological hallmarks of pp include cornoid lamella, dyskeratotic epidermal cells, and acantholysis of the basal layer. lymphocytic infiltrates and amyloid deposition in the papillary dermis have also been reported.7 while the genetics of all five primary forms of porokeratosis is proposed to be of an autosomal dominant mode of inheritance, the inheritance of pp has not been studied due to the small population affected by this newly recognized disease entity. however, a reported pair of brothers diagnosed with pp has been described and could suggest autosomal dominant inheritance.6 early detection is crucial for proper therapeutic and prognostic purposes as malignant variants of porokeratosis have been noted, with squamous cell carcinoma being the most common cutaneous malignancy.8 the most common indications for treatment of porokeratosis include pain, pruritis, and cosmetic concerns. treatment can be challenging, as lesions often relapse, similar to the other five subtypes of porokeratosis. treatment options include cryotherapy, topical corticosteroids, immunomodulators such as tacrolimus and 5-fu, calcipotriol, and finally retinoids.7 kawakami et al recently reported successful treatment of pp of the buttocks with topical 5% imiquimod treatment with resolution of lesions at the 12 month follow-up point.5 photodynamic therapy and methyl aminolevulinic acid were also reported to induce remission of pruritis and hyperkeratosis in two men with pp, with resolution of pruritis and hyperkeratosis for as long as 8 and 12 months respectively.9 however photodynamic therapy was not successful in treatment of our patient. additionally, successful induction of remission for 2 years was noted after treatment with an electric dermatome device.10 similarly, surgical excision was noted to result in remission for genitogluteal pp for 9 years.11 carbon dioxide lasers have also been used, however the few case reports that exist in the literature suggest that there is minimal long-term remission with recurrence of disease occurring shortly after treatment.12 in summary, pp remains a challenging diagnosis, as it is rare, newly described, and discussion conclusion skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 430 bears semblance to several other dermatological conditions. furthermore, pp lesions tend to recur and may be difficult to treat, with no established standard of care. we report the safe use of cryotherapy to relieve symptomatic pp lesions and highlight several other treatment modalities that can improve patient quality of life. conflict of interest disclosures: none funding: none corresponding author: robert phelps, md annenberg building room 308 1468 madison ave new york, ny 10029 email: robert.phelps@mountsinai.org references: 1. kamata y, maejima h, watarai a, et al. expression of bleomycin hydrolase in keratinization disorders. archives of dermatological research. 2012;304(1):31-38. 2. william d. james md tbm, dirk elston md. andrews' diseases of the skin: clinical dermatology. 11 ed: saunders; 2011. 3. tebet ac, oliveira tg, oliveira ar, moriya fs, oliveira jf, cuce lc. porokeratosis ptychotropica. anais brasileiros de dermatologia. 2016;91(5 suppl 1):134-136. 4. lucker gp, happle r, steijlen pm. an unusual case of porokeratosis involving the natal cleft: porokeratosis ptychotropica? the british journal of dermatology. 1995;132(1):150-151. 5. kawakami y, mitsui s. a case of porokeratosis ptychotropica: successful treatment with topical 5% imiquimod cream. clinical and experimental dermatology. 2017. 6. takiguchi rh, white kp, white cr, jr., simpson el. verrucous porokeratosis of the gluteal cleft (porokeratosis ptychotropica): a rare disorder easily misdiagnosed. journal of cutaneous pathology. 2010;37(7):802-807. 7. yeo j, winhoven s, tallon b. porokeratosis ptychotropica: a rare and evolving variant of porokeratosis. journal of cutaneous pathology. 2013;40(12):1042-1047. 8. maubec e, duvillard p, margulis a, bachollet b, degois g, avril mf. common skin cancers in porokeratosis. the british journal of dermatology. 2005;152(6):1389-1391. 9. fusta-novell x, podlipnik s, combalia a, et al. porokeratosis ptychotropica responding to photodynamic therapy: an alternative treatment for a refractory disease. photodermatology, photoimmunology & photomedicine. 2017;33(5):271-274. 10. scheiba n, enk a, proske s, hartschuh w. porokeratosis ptychotropica: successful treatment with the dermatome. dermatologic surgery : official publication for american society for dermatologic surgery [et al]. 2010;36(2):257-260. 11. huang sl, liu yh, chen w. genitogluteal porokeratosis. journal of the european academy of dermatology and venereology : jeadv. 2006;20(7):899-900. 12. yu hj, park kt, oh dh, kim js, park yw. a case of the hyperkeratotic variant of porokeratosis mibelli. the journal of dermatology. 2006;33(4):291-294. mailto:robert.phelps@mountsinai.org skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 79 short communication effectivity of e-learning as a resident education and engagement tool joanne s jacob, bs1, alexandria brown, bsa1, claire wiggins, md1,2, suzanne alkul, md3, audrey chan, md3,4, soo jung kim, md, phd3 1baylor college of medicine 2university of texas at austin dell medical school 3department of dermatology, baylor college of medicine 4department of pediatric dermatology, texas children's hospital the covid-19 pandemic impacted resident medical education by reducing opportunities for face-to-face contact with patients and colleagues. while virtual lectures helped bridge this gap, many learners have noted difficulty focusing and burnout from this format, a phenomenon dubbed “zoom fatigue.”1,2 in response, there has been a growing movement to engage the current generation of residents through platforms they identify with (e.g. text/chat groups) as an adjunct to traditional lectures.3 the baylor college of medicine department of dermatology implemented an e-learning initiative in 2020: a whatsapp and text messaging group with case-based and noncase-based questions along with answer sessions. the whatsapp platform was selected due to its end-to-end encryption of texts, wide availability across smartphone platforms, and administrative rights ensuring security of protected health information. for text messages, any identifiable images were not used. all messages were saved to each user’s device making it possible to review past questions and images. the inaugural group consisted of two faculty leaders and eleven dermatology residents. following the first nine months of the pilot educational initiative, a voluntary, anonymous survey, approved by the baylor college of medicine institutional review board was sent to the resident and faculty participants. survey responses were analyzed with descriptive statistics. a total of 3189 messages were sent during the first nine months of the whatsapp chat and texting groups, including 296 images of informational graphics. overall, 49.9% of messages were sent by the faculty and 50.1% were sent by the residents. in addition to case-based and non-based questions, the messaging group was used to share schedules and encouraging messages. the survey returned a 100% response rate of group participants. overall, 69.2% (9/13) of respondents found the initiative to be effective and 23.1% (3/13) deemed it very effective (figure 1). when compared to inperson discussion, 61.5% (8/13) of surveyed physicians found whatsapp/texting to be as effective as in-person discussion, while skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 80 figure 1. response to survey question “how effective do you find the dermatology resident whatsapp and texting groups as a case-based learning tool?” figure 2. response to survey question “how would you compare this experience to in-person, small group ‘problem-based learning’ activities, in terms of learning effectiveness?” 30.8% (4/13) thought it was less effective (figure 2). when asked about the strengths of the initiative, participants noted the ease of access to review material, sense of connectedness with faculty and residents, and the overall enjoyment it brought to their day. areas for improvement included that the messaging sessions were not as interactive as in-person learning and that it was occasionally difficult to participate in discussions depending on the resident’s rotation schedule. this elearning initiative has now evolved to involve five faculty, seven graduated residents working as practitioners, and twelve residents. not only has it been a useful adjunct tool to traditional lecture, but it has also served as a platform to discuss cases requiring multidisciplinary approaches. to maximize participation, 0% 0% 7.70% 69.20% 23.10% 0% 10% 20% 30% 40% 50% 60% 70% 80% very ineffective ineffective neither effecive nor ineffective effective very effective 30.80% 61.50% 7.70% 0.00% 10.00% 20.00% 30.00% 40.00% 50.00% 60.00% 70.00% whatsapp/texting is less effective for learning than inperson discussion. whatsapp/texting is about as effective for learning than inperson discussion. whatsapp/texting is more effective for learning than inperson discussion. skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 81 groups should identify optimal times for resident participation such as weekdays during the lunch hour or immediately after clinic duties. future considerations for the group include having educators use this tool to send post-lecture questions to reinforce material. we encourage programs to incorporate similar educational messaging programs, as most of our participants found it to be enjoyable, educational, and a bonding experience within the department. conflict of interest disclosures: none funding: none corresponding author: joanne s jacob 1 baylor plaza debakey bldg. m210 houston, tx 77030 fax: (713)-798-1518 joannej@bcm.edu references: 1. samara o, monzon a. zoom burnout amidst a pandemic: perspective from a medical student and learner. ther adv infect dis. 2021 jun 24;8:20499361211026717. doi: 10.1177/20499361211026717. pmid: 34249356; pmcid: pmc8239965. 2. asgari s, trajkovic j, rahmani m, zhang w, lo rc, sciortino a. an observational study of engineering online education during the covid-19 pandemic. plos one. 2021 apr 15;16(4):e0250041. doi: 10.1371/journal.pone.0250041. pmid: 33857219; pmcid: pmc8049279. 3. clavier t, ramen j, dureuil b, veber b, hanouz jl, dupont h, lebuffe g, besnier e, compere v. use of the smartphone app whatsapp as an e-learning method for medical residents: multicenter controlled randomized trial. jmir mhealth uhealth. 2019 apr 9;7(4):e12825. doi: 10.2196/12825. pmid: 30964435; pmcid: pmc6477573. about:blank presented at the fall clinical dermatology conference®; october 21−24, 2021; las vegas, nv, and virtual this is an encore of the 2021 eadv 30th congress poster and the 2021 npf research symposium poster this poster may not be reproduced without written permission from the authors.email for diamant thaçi, md: diamant.thaci@uksh.de deucravacitinib, an oral, selective tyrosine kinase 2 (tyk2) inhibitor, compared with placebo and apremilast in moderate to severe psoriasis: integrated laboratory parameter results from the phase 3 poetyk pso-1 and poetyk pso-2 trials diamant thaçi,1 kenneth gordon,2 melinda gooderham,3 bruce strober,4 neil j korman,5 subhashis banerjee,6 elizabeth colston,6 jonghyeon kim,6 john throup,6 akimichi morita7 1university of lübeck, lübeck, germany; 2medical college of wisconsin, milwaukee, wi, usa; 3probity medical research, waterloo, on, canada; 4yale university, new haven, ct, and central connecticut dermatology, cromwell, ct, usa; 5case western reserve university and university hospitals, cleveland, oh, usa; 6bristol myers squibb, princeton, nj, usa; 7nagoya city university, graduate school of medical sciences, nagoya, japan introduction • tyrosine kinase 2 (tyk2) is an intracellular enzyme that mediates signaling of key cytokines (interleukin [il]-23, il-12, and type i interferons) involved in psoriasis pathogenesis1,2 • deucravacitinib is a novel oral agent that selectively inhibits tyk2 via an allosteric mechanism by uniquely binding to the regulatory domain2 • in the phase 3 poetyk pso-1 and poetyk pso-2 trials, deucravacitinib was significantly more efficacious than placebo and apremilast and was well tolerated in patients with moderate to severe plaque psoriasis3 objective • the present analyses assessed the effects of deucravacitinib on hematologic, lipid, and chemistry parameters in blood in the poetyk trials methods study designs • poetyk pso-1 (nct03624127) and pso-2 (nct03611751) were phase 3, 52-week, double-blind, randomized, placeboand active comparator (apremilast)-controlled trials conducted globally (figure 1)2 — enrolled patients with moderate to severe plaque psoriasis (bsa, ≥10%; pasi, ≥12; spga, ≥3) were randomized 1:2:1 to receive oral placebo, deucravacitinib 6 mg once daily, or apremilast 30 mg twice daily during weeks 0−16 — blinded treatment switches occurred at week 16 and week 24 • patients receiving placebo were switched to deucravacitinib at week 16 • patients receiving apremilast who failed to meet trial-specific efficacy thresholds (pasi 50 in pso-1; pasi 75 in pso-2) were switched to deucravacitinib at week 24 figure 1. poetyk pso-1 and pso-2 study designs poetyk pso-1 (n=666) poetyk pso-2 (n=1020) deucravacitinib 6 mg qdplacebo (n=166) deucravacitinib 6 mg qd<pasi 50 apremilast 30 mg bidpasi 50 titrate*1 :2 :1 r an d om iz at io n weeks 16 24 520 deucravacitinib 6 mg qdplacebo (n=255) deucravacitinib 6 mg qd (n=511) deucravacitinib 6 mg qd<pasi 75 deucravacitinib 6 mg qd<pasi 75 deucravacitinib 6 mg qd deucravacitinib 6 mg qd placebob pasi 75 apremilast 30 mg bida (n=254) pasi 751 :2 :1 r an d om iz at io n weeks 16 24 520 1:1 deucravacitinib 6 mg qdplacebob deucravacitinib 6 mg qd (n=332) primary endpoint primary endpoint apremilast 30 mg bida (n=168) coprimary endpoints: pasi 75, spga 0/1 for deucravacitinib vs placebo at week 16 aapremilast was titrated from 10 mg qd to 30 mg bid over the first 5 days of dosing. bupon relapse (≥50% loss of week 24 pasi percentage improvement from baseline), patients were to be switched to deucravacitinib 6 mg qd. bid, twice daily; pasi 50, ≥50% reduction from baseline in psoriasis area and severity index; pasi 75, ≥75% reduction from baseline in pasi; qd, once daily; spga 0/1, static physician’s global assessment score of 0/1. laboratory assessments over weeks 0−16 • pooled data from poetyk pso-1 and pso-2 are presented • standard laboratory parameters in blood were evaluated — hematologic parameters: lymphocytes, neutrophils, platelets, and hemoglobin — lipid parameters: total cholesterol and triglycerides — chemistry parameters: creatine phosphokinase (cpk), creatinine, alt, and ast • toxicity grades 3—4 (common terminology criteria for adverse events [ctcae] version 5.0), shifts in toxicity grade, and discontinuations due to laboratory abnormalities were also assessed laboratory assessments over weeks 0−52 • standard laboratory parameters in blood were evaluated in patients enrolled in pso-1 who received continuous deucravacitinib treatment from baseline to week 52 results patient population • 666 and 1020 patients were randomized in pso-1 and pso-2, respectively, and were included in this analysis laboratory assessments over weeks 0−16 • overall, no clinically relevant trends were observed over weeks 0−16 in the levels of any of the assessed laboratory parameters (figure 2 and figure 3) • laboratory parameters remained within normal ranges for most patients throughout both trials figure 2. hematologic parameters, weeks 0−16 placebo apremilast 30 mg biddeucravacitinib 6 mg qd 0 1 2 3 4 5 lymphocytes lln uln m e an ± sd , 1 0 9 / l 1 2 4 8 12 160 weeks n= 419 393 369 368 355 842 792 775 750 739 421 398 379 368 365 12 13 14 15 16 hemoglobin lln uln m e an ± sd , g/ d l 1 2 4 8 12 160 weeks n= 419 393 371 368 356 842 797 779 753 747 421 401 381 369 366 0 2 4 6 8 neutrophils m e an ± sd , 1 09 /l lln uln 1 2 4 8 12 160 weeks n= 419 393 369 368 355 842 792 775 750 739 421 398 379 368 365 100 150 200 250 300 350 400 450 500 platelets m e an ± sd , 1 0 9 / l lln uln 1 2 4 8 12 160 weeks n= 418 388 367 364 355 842 784 769 747 742 421 398 377 368 365 poetyk pso-1 and pso-2 pooled data; weeks 0−16. bid, twice daily; lln, lower limit of normal; qd, once daily; uln, upper limit of normal. figure 3. lipid and chemistry parameters, weeks 0−16 creatinine 0.5 0.8 1.0 1.3 1.5 uln llnm e an ± s d , m g/ d l m e an ± s d , m g/ d l m e an ± s d , m g/ d l 1 2 4 8 12 160 weeks n= 419 394 382 368 358 842 803 793 765 758 422 402 385 377 369 0 200 400 triglycerides lln uln 8 160 weeks 100 150 200 250 300 uln total cholesterol lln 8 160 weeks n= 419 380 357 842 790 755 422 384 369 n= 419 380 357 842 790 755 422 384 369 0 250 500 750 1000 cpk lln uln 1 2 4 8 12 160 weeks n= 419 393 382 368 357 842 802 793 764 757 422 402 384 377 369 0 20 40 60 ast uln lln m e an ± s d , u /l m e an ± s d , u /l m e an ± s d , u /l 1 2 4 8 12 160 weeks n= 419 392 382 368 357 842 802 793 764 757 422 402 384 377 369 0 20 40 60 alt uln lln 1 2 4 8 12 160 weeks n= 419 391 382 368 357 842 802 793 764 757 422 402 384 377 369 placebo apremilast 30 mg biddeucravacitinib 6 mg qd poetyk pso-1 and pso-2 pooled data; weeks 0−16. no grade 4 cpk elevations were observed during consecutive study visits. bid, twice daily; cpk, creatine phosphokinase; lln, lower limit of normal; qd, once daily; uln, upper limit of normal. laboratory parameter grades and shifts (ctcae version 5.0) • grade ≥3 laboratory abnormalities occurred at low frequencies and were comparable across treatment groups (table 1) — triglyceride and cpk elevations were the most common grade ≥3 laboratory abnormalities and occurred at a similar incidence in each group • shifts of ≥2 ctcae grades (increases) from baseline were balanced overall and infrequent for all treatment groups — triglyceride shifts from grade ≤2 to grade ≥3 occurred at a low frequency and were comparable across groups: placebo, 1.3%; deucravacitinib, 1.7%; apremilast, 1.7% • there were patients with grade 3/4 elevations in triglyceride levels at baseline (placebo, 0.7%; deucravacitinib, 0.6%; apremilast, 0.7%), reflecting the comorbidity of metabolic syndrome associated with psoriasis — cpk shifts from grade ≤2 to grade ≥3 occurred at a low frequency and were comparable across groups: placebo, 0.7%; deucravacitinib, 1.3%; apremilast, 0.5% • cpk elevations from baseline to grade ≥1 postbaseline: placebo, 14.8%; deucravacitinib, 16.6%; apremilast, 11.0% • all cpk elevations were asymptomatic, nonserious, and resolved without treatment • most grade 3/4 cpk elevations were associated with increased recent physical activity during treatment table 1. grade ≥3 laboratory abnormalities, weeks 0−16 placebo (n=419) n (%) deucravacitinib (n=842) n (%) apremilast (n=422) n (%) parameter grade baseline week 16 baseline week 16 baseline week 16 lymphocyte count decreased 3 4 0 0 1 (0.2) 0 0 0 1 (0.1) 0 0 0 0 0 neutrophil count decreased 3 4 0 0 1 (0.2) 0 1 (0.1) 0 1 (0.1) 0 0 0 0 0 platelet count decreased 3 4 0 0 0 0 0 0 0 0 0 0 0 0 anemia 3 4 0 n/a 0 n/a 0 n/a 0 n/a 0 n/a 1 (0.2) n/a total cholesterol increased 3 4 0 0 0 0 0 0 0 0 0 0 0 0 triglycerides increased 3 4 2 (0.5) 1 (0.2) 6 (1.5) 0 4 (0.5) 1 (0.1) 13 (1.6) 2 (0.2) 3 (0.7) 0 8 (2.0) 0 cpk increased 3 4 1 (0.2) 0 3 (0.7) 1 (0.2) 1 (0.1) 0 5 (0.6) 6 (0.7) 1 (0.2) 0 2 (0.5) 1 (0.2) creatinine increased 3 4 0 0 0 0 0 0 0 0 0 0 0 0 alt increased 3 4 0 0 0 0 0 0 0 0 0 0 0 0 ast increased 3 4 0 0 0 0 0 0 1 (0.1) 0 0 0 1 (0.2) 0 poetyk pso-1 and pso-2 pooled data; weeks 0−16. cpk, creatine phosphokinase; n/a, not applicable because there is no hemoglobin value for ctcae grade 4 (life-threatening consequences; urgent intervention indicated). laboratory abnormality adverse events leading to discontinuation, weeks 0−16 • discontinuations due to laboratory abnormalities were low and balanced across treatment groups (table 2) table 2. laboratory abnormality adverse events leading to discontinuation, weeks 0−16 adverse event (preferred term) placebo (n=419) n (%) deucravacitinib (n=842) n (%) apremilast (n=422) n (%) lymphopenia 0 1 (0.1)a 0 blood cpk increased 0 1 (0.1)b 1 (0.2) hepatic function abnormal 0 1 (0.1)c 0 liver function test abnormal 1 (0.2) 0 0 ast increased 0 0 1 (0.2) poetyk pso-1 and pso-2 pooled data; weeks 0−16. cpk, creatine phosphokinase. apatient had grade 1 lymphocyte count decreased at baseline and grade 3 at week 4; treatment was discontinued and lymphocyte count returned to grade 2; there were no associated infection adverse events. bpatient had elevated cpk at screening (1796 u/l) and baseline (932 u/l). cpatient had a medical history of fatty liver disease and recent alcohol use (increased alcohol consumption due to ankle injury [2x usual]). laboratory assessments over weeks 0−52 • no clinically relevant cumulative trends were observed in any assessed laboratory parameters in pso-1 patients who were randomized to deucravacitinib at baseline and who continued to receive treatment until week 52 (figure 4 and figure 5) • discontinuation rates due to laboratory abnormalities were not increased between weeks 16−52 vs weeks 0−16 figure 4. hematologic parameters in patients receiving deucravacitinib (pso-1), weeks 0−52 deucravacitinib 6 mg qd 0 1 2 3 4 5 weeks 1 2 4 8 12 160 20 24 28 32 36 40 44 48 52 lln uln lymphocytes n= 332 317 312 303 295 298 283 286 280 270 257 259 255 254 n= 332 317 312 303 295 298 283 286 280 270 257 259 255 254 0 2 4 6 8 weeks 1 2 4 8 12 160 20 24 28 32 36 40 44 48 52 lln uln neutrophils hemoglobin 12 13 14 15 16 17 weeks 1 2 4 8 12 160 20 24 28 32 36 40 44 48 52 lln uln n= 332 318 313 305 297 299 285 291 283 272 260 261 258 257n= 332 314 311 303 295 298 285 287 282 270 260 257 256 254 100 150 200 250 300 350 400 450 500 weeks 1 2 4 8 12 160 20 24 28 32 36 40 44 48 52 lln uln platelets m e an ± s d , 1 0 9 /l m e an ± s d , g/ d l m e an ± s d , 1 0 9 /l m e an ± s d , 1 0 9 /l graphs display as observed data for patients randomized to deucravacitinib at baseline in pso-1 who continued treatment until week 52. lln, lower limit of normal; qd, once daily; uln, upper limit of normal. figure 5. lipid and chemistry parameters in patients receiving deucravacitinib (pso-1), weeks 0−52 deucravacitinib 6 mg qd 0.5 1 1.5 weeks 1 2 4 8 12 160 20 24 28 32 36 40 44 48 52 lln uln creatinine n= 332 322 319 308 303 304 295 293 288 278 268 265 266 266 0 250 500 750 1000 1250 1500 weeks 1 2 4 8 12 160 20 24 28 32 36 40 44 48 52 lln uln cpk n= 332 322 319 308 302 304 293 292 288 278 267 266 266 263 0 20 40 60 weeks 1 2 4 8 12 160 20 24 28 32 36 40 44 48 52 lln uln alt n= 332 322 319 308 302 304 292 292 287 277 267 265 266 263 100 150 200 250 weeks 8 160 24 52 total cholesterol uln lln n= 332 317 301 294 262 m e an ± s d , m g/ d l m e an ± s d , m g/ d l m e an ± s d , u /l m e an ± s d , u /l graphs display as observed data for patients randomized to deucravacitinib at baseline in pso-1 who continued treatment until week 52. cpk, creatine phosphokinase; lln, lower limit of normal; qd, once daily; uln, upper limit of normal. conclusions • patients receiving deucravacitinib treatment showed no meaningful changes in multiple hematologic, chemistry, and lipid parameters in the blood over weeks 0−16 in 2 large phase 3 trials in psoriasis (poetyk pso-1 and pso-2) — discontinuations due to laboratory abnormalities were rare and balanced across treatment groups • no trends were evident for any laboratory parameter with continued deucravacitinib treatment over 52 weeks • these results suggest that routine laboratory monitoring is not warranted during deucravacitinib treatment references 1. nogueira m et al. drugs 2020;80:341-351. 2. burke jr et al. sci transl med 2019;11:1-16. 3. armstrong a et al. presented at the annual meeting of the american academy of dermatology; 2021. acknowledgments • we would like to thank the patients and investigators who participated in these trials. • these clinical trials were sponsored by bristol myers squibb. professional medical writing from lisa feder, phd, and editorial assistance were provided by peloton advantage, llc, an open health company, parsippany, nj, usa, and were funded by bristol myers squibb. relationships and activities • dt: advisory board, principal investigator, and lecture fees: abbvie, almirall, amgen, biogen idec, boehringer ingelheim, bristol myers squibb, celgene, ds pharma, eli lilly, galapagos, galderma, janssen-cilag, leo pharma, novartis, pfizer, regeneron, roche-posay, samsung, sandoz-hexal, sanofi, and ucb • kg: grant support and consulting fees: abbvie, boehringer ingelheim, bristol myers squibb, celgene, eli lilly, janssen, novartis, and ucb; consulting fees: amgen, almirall, dermira, leo pharma, pfizer, and sun pharma • mg: advisory board, principal investigator, and lecture fees: abbvie, galderma, leo pharma, pfizer, and regeneron; advisory board and lecture fees: actelion pharmaceuticals; principal investigator and consulting fees: akros pharma; advisory board, principal investigator, lecture fees, and consulting fees: amgen, boehringer ingelheim, celgene, eli lilly, janssen, novartis, sanofi genzyme, and valeant; principal investigator: arcutis, bristol myers squibb, dermira, glaxosmithkline, medimmune, merck, roche laboratories, and ucb; principal investigator and lecture fees: glenmark • bs: honoraria or consultation fees: abbvie, almirall, amgen, arcutis, arena, aristea, asana, boehringer ingelheim, bristol myers squibb, connect biopharma, dermavant, eli lilly, equillium, glaxosmithkline, immunic therapeutics, janssen, leo pharma, maruho, meiji seika pharma, mindera, novartis, ortho dermatologics, pfizer, regeneron, sanofi genzyme, sun pharma, ucb, and ventyxbio; speaker: abbvie, janssen, lilly, sanofi genzyme; scientific co-director (consulting fee): corevitas’ psoriasis registry; investigator: abbvie, cara, corevitas’ psoriasis registry, dermavant, eli lilly/dermira, and novartis • njk: advisory board, consulting fees: abbvie, boehringer ingelheim, bristol myers squibb, celgene, eli lilly, janssen, leo pharma, novartis, principia, regeneron, sanofi genzyme, sun pharma, and ucb; grant support/principal investigator: abbvie, amgen, argenx, bristol myers squibb, celgene, chemocentryx, eli lilly, galderma, kyowa hakko kirin, leo pharma, menlo, principia, prothena, rhizen, syntimmune, trevi, and xbiotech; speaker: abbvie, eli lilly, janssen, novartis, regeneron, and sanofi genzyme • sb, ec, jk, and jt: employees and shareholders: bristol myers squibb • am: grant/research support, consultant, speakers bureau: abbvie, boehringer ingelheim, bristol myers squibb, celgene, eisai, eli lilly, janssen, kyowa hakko kirin, leo pharma, maruho, mitsubishi tanabe, nichi-iko, nippon kayaku, novartis, pfizer, sun pharma, taiho pharmaceutical, torii pharmaceutical, ucb, and ushio skin july 2021 1201 proof returned skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 410 brief article a case of hydroxyurea-associated cutaneous only polyarteritis nodosa angela h. wei, bs1, sheena t. hill, md, mph1, dennis a. vidmar, md1,2 1department of dermatology, university hospitals, cleveland medical center 2department of dermatology, louis stokes cleveland department of veterans affairs medical center vasculitis refers to a group of autoimmune disorders that are characterized by inflammation of blood vessels, and can occur as a primary disease or secondary to other etiologies.1 vasculitis can affect vessels of various types, sizes, and locations, and these features help classify the disease.1 polyarteritis nodosa (pan) is a form of vasculitis that affects medium-sized arteries.2 in its classic form, pan is a systemic disease that affects several organs; the skin, heart, liver, gastrointestinal tract, kidneys, and central nervous system are most commonly affected.2 pan can be idiopathic or secondary to other disease processes, such as streptococci, mycobacteriae, viral agents such as hepatitis b and c, hiv, parvovirus b19, or even some medications.2 cutaneous polyarteritis nodosa (cpan) is a variant of pan that affects only the small and medium-sized arteries of the dermis and subcutis and is restricted to localized regions, typically the extremities.1, 3 the diagnosis is made in the presence of clinical features including tender cutaneous nodules and livedo reticularis, and only after exclusion of other organ system involvement.3 herein, we present a rare case of hydroxyurea-related cpan. a 72-year-old man presented with a one-year history of recurrent, tender, livedo-like bruising on his right dorsal thigh, which progressed to his left thigh. his medical history was significant for polycythemia vera (pv), atrial fibrillation, long-standing hypertension-related chronic kidney disease abstract hydroxyurea is a common antineoplastic agent used to treat several cancers and myeloproliferative conditions, such as chronic myelogenous leukemia and polycythemia vera. long-term use has been associated with several adverse cutaneous reactions, including skin ulcers, xerosis, and hyperpigmentation. we report a patient who presented with tender, indurated, erythematous nodules in his legs and thighs who had been taking hydroxyurea for 8 years to treat polycythemia vera. biopsy revealed medium-sized arteries with intramural neutrophils, eosinophils, and edema. histopathology and clinical features were highly suggestive of cutaneous polyarteritis nodosa (cpan). discontinuation of hydroxyurea resulted in full resolution of his lesions. introduction case report skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 411 stage iii, well-controlled type 2 diabetes, dyslipidemia, obstructive sleep apnea, and untreated prostate cancer (under observation). his medications included atorvastatin, amlodipine, metoprolol, propafenone, ranitidine, ropinirole, sertraline, warfarin, and vitamin d. his pv was initially treated with hydroxyurea 500 mg/day and phlebotomy for 8 years. a monitoring bone marrow biopsy in 2017 revealed a jak2 mutation (v617f). initial punch biopsies from his right thigh showed deep dermal periarterial fibrosis and arterial thrombosis with early organization. the underlying subcutis displayed noninflammatory foci of vascular proliferation, suggesting small, resolving arterial thromboses. four months later, he reported new tender nodules of both anterior thighs (figure 1). doppler ultrasound of both legs were normal. figure 1. three months later, he had additional tender nodules on his left leg, and a new rash on his back, buttocks, and posterior legs. there were also indurated, red nodules on his left flank and left lateral distal thigh, and tender reticulate erythema of his left dorsal foot. a second set of punch biopsies showed medium-sized arteries with intramural edema, surrounded by neutrophils and some eosinophils (figure 2a and 2b). two medium-sized arteries displayed intraluminal thrombi, with similar involvement of thinnerwalled vessels. figure 2. a) h&e, 100x b) h&e 200x complete blood count showed a leukocytosis of 25,600, but no anemia or platelet abnormalities. crp, esr, and c3, c4, and ch50 levels were normal. anti-neutrophil cytoplasmic (anca) antibodies, anti-histone antibody, ana panel, lupus anticoagulant, anti-phospholipid panel, anti-cyclic citrullinated peptide antibody, hepatitis b, hepatitis c, hiv, cryoglobulins, cryofibrinogen, and quantitative immunoglobulin g, a, and m were all negative/normal. cmp was normal except for a b skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 412 a low estimated glomerular filtration rate (egfr) of 40 ml/min. multiple urinalyses were normal. abdominal mri showed foci of renal artery vascular narrowing but were not felt by the radiologist to be vasculitic. chest ct without contrast was non-contributory. the integration of the history, histopathology, imaging, and laboratory findings favored the diagnosis of cpan. despite starting colchicine, he developed new lesions on his left thigh, left buttock, and flank over the next several months. concomitantly, his egfr declined to 23 ml/min. given that the vasculitis was limited to the skin and had not improved, colchicine was discontinued. since a bone marrow biopsy in 2017 showed a jak2 mutation, his pv treatment was changed to the jak kinase inhibitor, ruxolitinib. within 11 weeks, the nodules began to resolve. a few weeks later, only non-tender, reticulate pigmentation remained. ruxolitinib controlled his pv. his egfr stabilized at 40 ml/min, likely due to discontinuation of the colchicine. the nephrologist did not believe his chronic kidney disease was related to cpan renal involvement. over the next six months, the skin changes completely resolved. based on the rapid resolution of the tender cutaneous nodules after discontinuing hydroxyurea, we conclude that the cpan resulted from hydroxyurea use. hydroxyurea is used to treat solid tumors and myeloproliferative diseases, such as chronic myelogenous leukemia and pv.4 it is an antimetabolite that inhibits ribonucleotide reductase, an enzyme required for dna synthesis. while generally well-tolerated, there have been reports of adverse cutaneous reactions after prolonged use in roughly 5% of patients.4 these include skin eruptions, skin ulcers, xerosis, diffuse hyperpigmentation, alopecia, nail dystrophy, dermatomyositis-like syndrome, and an increased risk of squamous and basal cell carcinoma.4 one of the most serious complications is painful ulcers of the lower legs that can be severe and even lifethreatening.5 leg ulcers with hydroxyurea use have occasionally been associated with leukocytoclastic vasculitis, with at least one report of medium vessel vasculitis and panniculitis.4-6 cessation of hydroxyurea was necessary for resolution of nearly all of the reported cases, with or without documented vasculitis. vasculitis is commonly drug-induced and often results in cutaneously-limited vasculitis.7 although the pathogenesis is not clear, the similar clinical profiles of druginduced vasculitis suggest a common mechanism, such as formation of immune complexes.7 many medications are implicated in drug-induced vasculitis, including antimicrobials, antithyroid drugs, and tumor necrosis factor inhibitors.7 in particular, there have been several cases of minocycline-induced cutaneous and systemic pan-like vasculitis and one case of empagliflozin-induced cpan.8, 9 while the mechanism of most hydroxyureainduced skin damage is not well characterized, it is thought that the inhibition of dna synthesis results in damage of the basal layer of the epidermis.10 this, combined with trauma, may cause poorlyhealing ulcers. other proposed mechanisms include platelet dysregulation and macrocytosis, leading to disrupted microcirculation and microthrombi formation.10 discussion skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 413 hydroxyurea is a commonly prescribed antimetabolite used to treat many oncologic and hematologic diseases and has been associated with various adverse cutaneous reactions. we report a unique case of hydroxyurea-induced vasculitis best classified as cpan. this case contributes to our understanding of the range of adverse cutaneous effects of the medication and can aid in the clinical management of patients taking long-term hydroxyurea. list of abbreviations and acronyms: anca antineutrophil cytoplasmic antibodies cmp complete metabolic panel cpan cutaneous polyarteritis nodosa crp c-reactive protein egfr estimated glomerular filtration rate esr erythrocyte sedimentation rate hiv human immunodeficiency virus jak2 janus kinase 2 pan polyarteritis nodosa pv polycythemia vera conflict of interest disclosures: none funding: none corresponding author: sheena t. hill, md, mph department of dermatology university hospitals cleveland medical center 11100 euclid avenue lakeside 3500 cleveland, oh 44106 phone: 216-844-8200 fax: 216-844-8993 email: sheena.hill@uhhospitals.org references: 1. okazaki t, shinagawa s, mikage h. vasculitis syndrome-diagnosis and therapy. j gen fam med. 2017 mar 24;18(2):72-78. doi: 10.1002/jgf2.4. 2. hernández-rodríguez j, alba ma, prietogonzález s, cid mc. diagnosis and classification of polyarteritis nodosa. j autoimmun. 2014 feb-mar;48-49:84-9. doi: 10.1016/j.jaut.2014.01.029. 3. bauzá a, españa a, idoate m. cutaneous polyarteritis nodosa. br j dermatol. 2002 apr;146(4):694-9. doi: 10.1046/j.13652133.2002.04624.x. 4. mattessich s, ferenczi k, lu j. successful treatment of hydroxyurea-associated panniculitis and vasculitis with low-dose methotrexate. jaad case rep. 2017 sep 8;3(5):422-424. doi: 10.1016/j.jdcr.2017.06.009 5. young hs, kirby b, stewart ej. aggressive, extensive, vasculitic leg ulceration associated with hydroxyurea therapy and a fatal outcome. clin exp dermatol. 2001 nov;26(8):664-7. doi: 10.1046/j.1365-2230.2001.00913.x. 6. sirieix me, debure c, baudot n, et al. leg ulcers and hydroxyurea: forty-one cases. arch dermatol. 1999 jul;135(7):818-20. doi: 10.1001/archderm.135.7.818. 7. radić m, martinović kaliterna d, radić j. druginduced vasculitis: a clinical and pathological review. neth j med. 2012 jan;70(1):12-7. 8. kermani ta, ham ek, camilleri mj, warrington kj. polyarteritis nodosa-like vasculitis in association with minocycline use: a singlecenter case series. semin arthritis rheum. 2012 oct;42(2):213-21. doi: 10.1016/j.semarthrit.2012.03.006. 9. to d, bradshaw s, lipson j. case report of empagliflozin-induced cutaneous polyarteritis nodosa. j cutan med surg. 2018 sep/oct;22(5):516-518. doi: 10.1177/1203475418760457. 10. ogawa y, akiyama m. non-infectious panniculitis during hydroxyurea therapy in a patient with myeloproliferative disease. acta derm venereol. 2016 may;96(4):566-7. doi: 10.2340/00015555-2292. conclusion covid-19 training on train trainings on infection prevention and control, ppe, self-care/mental health for professionals openwho free covid-19 training courses and exercises, patient handouts/stickers/ posters/fun activities latest research, free cme, public health guidance and patient information with a special jama dermatology section available free evidence based skin disease booklets to order or download for your patients and educational grants and funding information database of clinical studies available around the world new symptom tracker launched to fight covid-19 provides real time data for treatment planning and updated recommendations due to covid-19, extended use of ppe introduced an increased risk of dermatological conditions among health care workers. many essential workers experience adverse skin reactions (asrs) to the hands and face.1 additionally, increased hygiene measures, such as utilization of 60% alcohol based hand sanitizers lead to the disruption of skin flora and natural protections of the skin barrier.2 subsequently, bacteria, fungi, and viruses, such as the coronavirus, can penetrate through the skin into the bloodstream causing additional comorbidities.3 though 90% of healthcare workers experience symptoms associated with hand eczema less than 15% recognize the symptoms as onset of disease.2 introduction 54 year old female essential worker with a history of atopic dermatitis presents with a 6 week worsening of hand dermatitis due to frequent job related hand washing and sanitizing (~20x/day). hand dermatitis is unresponsive to previously effective long term atopic dermatitis treatment plan: case report information otc cleanser (cetaphil® pro) twice daily otc moisturizer (cetaphil® pro eczema) twice daily and as needed desoximetasone (topicort®) ointment 0.05% twice daily for flares loratadine (claritin®)10mg daily adult multivitamin daily exam signs and symptoms pruritis, pain papules erythematous plaques and scaling excoriation fingertip fissures results intervention/ treatment initial visit 2 week visit prescribe physiologically balanced lipid skin barrier repair emulsion (epiceram®) twice daily and as needed continued otc cleanser (cetaphil® pro) twice daily continued desoximetasone (topicort®) ointment 0.05% twice daily for flares continued loratadine (claritin®) 10mg daily continued adult multivitamin daily covid-19 resources and guidelines discussion this case study demonstrates that a focus on proper barrier repair, which includes physiologically balanced lipids in a 3:1:1 ratio (ceramide:free fatty acid:cholesterol) delivered over time, is an important treatment option for asrs due to frequent ppe use and hand washing/sanitizing not adequately responding to current treatment measures inclusive of topical steroids and over the counter moisturizers. conclusion due to the covid-19 pandemic essential workers are at increased risk of developing various cutaneous conditions. utilizing a 3:1:1 prescription skin barrier repair emulsion that delivers physiologic lipids is an option for quick and sustained resolution of dermatoses. references 1. hu k, fan j, li x, gou x, li x, zhou x. the adverse skin reactions of health care workers using personal protective equipment for covid-19. medicine (baltimore). 2020;99(24):e20603. doi:10.1097/md.0000000000020603 2. guertler a, moellhoff n, schenck tl, et al. onset of occupational hand eczema among healthcare workers during the sars-cov-2 pandemic: comparing a single surgical site with a covid-19 intensive care unit. contact dermatitis. 2020;83(2):108-114. doi:10.1111/cod.13618 3. baldwin h, aguh c, andriessen a, et al. atopic dermatitis and the role of the skin microbiome in choosing prevention, treatment, and maintenance options. j drugs dermatol. 2020;19(10):935-940. doi:10.36849/jdd.2020.10.36849/ jdd.2020.5393 covid-19 pandemic and personal protection equipment (ppe): a focus on treatment of essential workers with hand dermatitis heather roebuck, dnp, fnp-bc, faanp roebuckderm, west bloomfield, mi initial visit 2 week visit the author wishes to thank dr. christina cognata smith for her editorial assistance and support throughout this educational endeavor. skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 129 rising derm stars® post-operative pain after mohs micrographic surgery: analyzing physician perceptions of postoperative pain and how those perceptions affect opioid prescribing practices joshua d. eikenberg md, mph1, savannah taylor, ms, kyle a. prickett, md, mariana a. phillips, md 1department of dermatology, virginia tech carilion school of medicine, roanoke, va background/objectives: opioid abuse in the united states has become an epidemic. opioid prescribing by dermatologists is generally limited to the surgical setting. nevertheless, there is evidence to suggest that thousands of patients are at risk for long term opioid use as a result of prescriptions that they receive from dermatologists.1 however, little is known about dermatologists’ perceptions of postoperative pain and how they correlate with patient perceptions of pain. it is also unclear if physician perceptions of patient pain affect opioid prescribing practices or if receiving prescription opioids affects patient reported satisfaction with pain control. the objective of this study was to determine how physician perceptions of postoperative pain after mohs micrographic surgery correlate with patient reported pain and affect physician opioid prescribing practices. we also sought to determine if patients receiving opioids were more likely to be satisfied with their level of pain control. methods: patients presenting for mohs micrographic surgery completed pain surveys using the numerical rating scale (010) on the evening of (day 0) and the first four nights after the procedure. patients also rated their satisfaction with their pain control on a 0-10 scale. after the repair, the physician recorded a prediction of the patient’s pain level on day 0 using the numerical rating scale (0-10). the predicted pain was compared to the recorded patient pain. the age, sex, diagnosis, surgery site, postoperative size, closure type, and oral analgesics used were recorded. results: a total of 260 of the 396 patients recruited completed the surveys. there were no significant differences in post-operative pain based on patient characteristics, closure type, or tumor location. there is no significant difference between mean day 0 patient reported pain (2.7±2.5) and physician predicted pain (2.9 ± 1.1; p = 0.13). correlation between physician predicted pain and patient reported pain was significant (p < 0.0001) but the correlation coefficient was relatively small (r =0.27). the majority (70.0%) of physician predictions were within 2 points or less of patient reported pain and 45.0% of physician predictions were within 1 point. however, 30.3% of physician predictions differed by 3 or more points from patient reported pain. opioids were only prescribed to 45 patients (17.3%). the mean skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 130 predicted pain score of patients who were prescribed opioids (3.4 ± 1.2) was significantly higher than those who were not prescribed opioids (2.8 ± 1.1; p = 0.0018). there was no significant difference in patient satisfaction scores between those who were prescribed opioids and those who were not (p = 0.688). table 1: patient characteristics (n = 260). characteristic value age, mean ± standard deviation 70.03 ± 10.53 age, n (%) <60 37 (14.7) 60-69 85 (33.9) 70-79 88 (33.2) ≥80 50 (20.2) sex, n (%) male 94 (36.2) female 166 (64.8) diagnosis, n (%) basal cell carcinoma 187 (71.9) squamous cell carcinoma 58 (22.3) squamous cell carcinoma in situ 12 (4.6) melanoma in situ 1 (0.4) adnexal carcinoma 1 (0.4) atypical fibroxanthoma 1 (0.4) site, n (%) nose 64 (24.6) cheek 47 (18.1) ear 34 (13.1) forehead 32 (12.3) scalp 17 (6.5) temple 14 (5.4) lip 10 (3.8) neck 10 (3.8) chin 9 (3.5) leg 8 (3.1) eyelid 6 (2.3) hand 4 (1.5) back 2 (0.8) arm 1 (0.4) forearm 1 (0.4) foot 1 (0.4) number of stages, n (%) 1 175 (67.3) 2 67 (25.8) 3 13 (5.0) 4 5 (1.9) defect size in cm2 n (%) <1.0 17 (6.5) 1.0-1.9 48 (18.5) 2.0 – 2.9 56 (21.5) >3.0 139 (53.4) closure type, n (%) complex linear 155 (59.6) graft 42 (16.2) flap 40 (15.4) secondary intention 17 (6.5) graft with cartilage 4 (1.5) conclusion: physician predictions of perceived patient pain were within two points of patient reported pain in most cases. physicians were more likely to prescribe opioids for patients with higher predicted pain. patients who were prescribed opioids were no more satisfied with their level of pain control than patients who did not receive opioids. patient characteristics, tumor location, and closure type were not associated with patient reported pain score. references: 1. cao s, karmouta r, and li dg. opioid prescribing patterns and complications in the dermatology medicare population. jama dermatol. 2018;154(3):317-322. skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 410 research letters adolescent sun protection behaviors and beliefs roya s. nazarian, ba,1 michael pan, md,1 sarah utz, md,2 lauren geller, md1 1department of dermatology, icahn school of medicine at mount sinai, new york, ny 2department of dermatology, wayne state school of medicine, detroit, mi skin cancer is the most common malignancy in the united states, with a rising incidence, including in children and adolescents at a rate of 2% per year.1 exposure to ultraviolet (uv) radiation, either from natural sunlight or indoor tanning, is a known risk factor for the development of skin cancer. research has found that only 30% of adolescents report regular use of sunscreen and that 70-80% of them had sunburns the previous summer.2 previous studies on photo protection have utilized data from nationwide surveys of high school students; it is unclear whether these abstract importance: the incidence of melanoma and non-melanoma skin cancer has increased among children and adolescents. studies in the pediatric population have shown low rates of sun protection with modest improvement over the past several decades. objective: this descriptive study characterizes photo protection behaviors and knowledge, specifically among pediatric dermatology patients in order to identify gaps in knowledge and guide discussion for health providers. methods: adolescents ages 12 to 20 completed surveys, which evaluated use of sun protection, beliefs about tanning and skin cancer, and sources of information. results: results demonstrated that only nine percent of participants reported daily, year-round use of sunscreen. the majority (71%) reported use only during the summer months or when spending prolonged periods of time outdoors. rates of indoor tanning were lower than reported in the literature, with only one percent reporting indoor tanning use. the majority of patients reported family members were the primary source of sun protection education. conclusions and relevance: the authors conclude that while adolescents receiving care in the pediatric dermatology setting demonstrate sufficient knowledge about skin cancer prevention, adherence remains low. this study identified family members as the primary source of sun protection knowledge. dermatologists should consider increased parental education to improve adolescent patient behavior. introduction skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 411 trends accurately reflect the beliefs of adolescents who seek dermatologic care, who may be hypothesized to practice better sun protection. our study aims to characterize the behaviors and beliefs specifically of adolescents frequenting a pediatric dermatology clinic in order to better guide educational efforts by physicians. 105 subjects age 12-20 were recruited from an outpatient pediatric dermatology practice at the icahn school of medicine at mount sinai in new york, where the study received institutional review board approval. participants completed a 26-question survey, which solicited information about demographics, knowledge of proper photo protection behavior, and implementation of sun protective practices, including use of sunscreen, frequency of application, use of indoor tanning, and use of sun protective clothing. the mean age of the participants was 14.46 years, with 61% identifying as female and 65% as caucasian. twenty-eight participants (27%) reported a family history of skin cancer. of those, 50% reported a family history of melanoma, and 40% reported basal cell carcinoma. eighty-seven participants (87%) self-reported a lifetime history of at least one sunburn, and 54 participants (51%) reported a history of sunburn one or more times in the past year alone (table 1). most participants did report some use of sunscreen, however, only 9% wore sunscreen daily and year-round, with the majority (71%) only doing so during the summer months or when spending prolonged periods of time outdoors. of those who reported any use of sunscreen, half reapplied sunscreen multiple times throughout the day. use of other photo protection measures was low, with 39% reporting use of sunglasses and 25% reporting use of hats. eighteen percent wore sun protective clothing. only one adolescent in our study (1%) reported use of indoor tanning, however, they had done so 17 times (table 2). analysis of sun protection attitudes and beliefs revealed that the majority had accurate knowledge about sunscreen, tanning, and skin cancer (table 2). many participants reported that family members, especially parents, had discussed sun protection (90%) and skin cancer (57%) with them. much fewer reported that teachers had done so (32% and 37%). table 1. basic demographics of the study population (n=105) characteristic n % age in years (n=105) 12-15 72 69 16-20 33 27 sex (n=104) male 41 39 female 63 61 race (n=105) caucasian 70 67 african american 9 9 latino 14 13 asian 5 5 other 7 7 skin's reaction to sun (n=105) always burns, never tans 10 10 usually burns, sometimes tans 23 22 methods results skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 412 sometimes burns, tans evenly everywhere 15 14 burns occasionally, always tans 24 23 very rarely burns, always tans 30 29 never burns, never tans 3 3 hair color (n=105) brown/black 83 79 blonde 21 20 red 1 1 eye color (n=104) brown 59 57 blue 19 18 green 9 9 hazel 17 16 family history of skin cancer (n=104) yes 28 27 no 66 63 unsure 10 10 table 2. sun protective behavior and knowledge behavioral characteristic n % frequency of sunscreen use (n=105) daily year-round 9 9 daily during summer months only 9 9 only when outdoors for prolonged time 58 55 only when at the beach 13 12 rarely 12 11 never 4 4 skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 413 frequency of reapplication of sunscreen (n=105) once a day 47 45 multiple times a day 47 45 i don’t wear sunscreen 11 10 strength of spf (n=90) spf lower than 15 1 1 spf 15 to 25 11 10 spf 30 to 45 32 30 spf 50+ 46 44 use of hat when outdoors (n=105) always 4 4 usually 22 21 rarely 53 50 never 26 25 use of sunglasses when outdoors (n=105) yes, always 13 12 usually 28 27 rarely 37 35 never 27 26 use of sun protective clothing (n=104) yes 19 18 no 85 82 lifetime history of sunburn (n=105) yes, once 28 26 yes, more than once 59 55 no 18 19 history of sunburn in last year (n=105) yes, once 34 32 skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 414 yes, more than once 20 19 no 51 49 history of indoor tanning (n=105) never 104 99 once 0 0 2-5 times 0 0 5-10 times 0 0 > 10 times 1 1 knowledge and attitudes n % i feel healthier with a tan (n=99) agree 13 13 disagree 86 87 i feel more attractive when i am tan (n=98) agree 39 40 disagree 59 60 i can stay out in the sun as long as i want if i wear sunscreen (n=103) agree 21 20 disagree 82 80 sunscreen is waterproof (n=100) agree 27 27 disagree 73 73 getting a “base tan” from indoor tanning can prevent sunburn later in the summer (n=97) agree 5 5 disagree 92 95 if you have darker skin you cannot get skin cancer (n=100) agree 6 6 disagree 94 94 skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 415 sources of sun protective knowledge n % have your teachers in school talked to you about sun protection (n=104) yes 33 32 no 71 68 have your teachers in school talked to you about skin cancer (n=104) yes 38 37 no 66 63 has anyone in your family talked to you about sun protection (n=104) yes 93 90 no 11 10 has anyone in your family talked to you about skin cancer (n=104) yes 59 57 no 45 43 results demonstrate that photo protection amongst pediatric dermatology patients remains low, and rates of sunburns are high. overall prevalence of daily sunscreen use throughout the year was low (9%), similar to data from national surveys on adolescent health, which found that 7-14% of high school adolescents regularly apply sunscreen.3 this rate is much lower when compared to adults in the general us population, in which 14.3% of men and 29.9% of women report daily sunscreen use.4 more specifically, proper use of photoprotection, such as sunscreen, remains a challenge. healthcare providers should encourage reapplication of sunscreen and year-round use, which is the current recommendation by the american academy of dermatology.5 additionally, our study found that adolescents are infrequent users of sun-protective clothing, with many citing unfamiliarity with this concept in the free text response. this highlights a specific area for improved patient education. the prevalence of indoor tanning has decreased nationwide studies in the past decade, and our results suggest that adolescents frequenting a pediatric dermatology clinic are less likely to use indoor tanning, as only 1% of participants reported use of indoor tanning, compared to 7% of u.s. high school in the general population.6 this suggests indoor tanning should not be the focus of in-office discussions by health providers.6 however, our data may be biased, given that the study population was recruited from an urban center in the northeast, where tanning bed discussion skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 416 conclusion usage has historically been less popular compared to southern and rural areas. with regards to skin cancer prevention knowledge, the vast majority of study participants had accurate information about proper photo protection and skin cancer prevention, despite poor practices. this suggests that positive perceptions of tanned skin may have the greatest influence on adolescent sun behavior, even in a population frequenting a pediatric dermatology clinic.7 in fact 40% of participants reported they feel more attractive with a tan, which corroborates the current literature that self-image may impair safe practice, despite adequate knowledge (table ii). this implies that healthcare providers should address whether tanned skin is valued by their patient as a standard of beauty prior to forming a preventative educational plan. finally, this study identified parents rather than teachers as the primary source of skin cancer education in adolescents. interestingly, sunscreen usage has been shown to decrease as adolescents get older, possibly a result of less parental supervision.8 we believe earlier educational efforts are needed. however, one study found that only 49% of parents reported ever discussing skin cancer prevention with their pediatrician and that sun protection ranked lowest among preventative topics discussed by pediatricians.9 we hope these findings will guide the educational efforts of dermatologists and pediatricians alike to prioritize sun protection when educating parents. limitations of this study include the use of a non-validated survey. additionally, there may be selection bias as subjects were largely caucasian and from an urban center. it should be noted that while the majority of participants were caucasian, almost 25% self-identified as african american or latino. studies have shown that african american subgroups may be less aware of preventative skin care and practice fewer sun protective behaviors, and these differing practices may have skewed the photoprotection behavior results for the overall cohort.10 our study suggests that adolescent patients who seek dermatologic care are poor practitioners of photo protection, consistent with the general adolescent population. while many report some use of sunscreen, proper application and reapplication is lacking and the use of sun protective clothing is poor. furthermore, many still maintain the belief that they are more attractive with a tan, highlighting self-image as an important target in sun safety education. healthcare providers should continue to educate patients and their parents to modify these behaviors. conflict of interest disclosures: none funding: none corresponding author: lauren geller, md 5 e 98th street, 5th floor new york ny 10029 tel: (212) 241-9728 fax: (212) 987-1197 email: lgeller.md@gmail.com references: 1. wong jr, harris jk, rodriguez-galindo c, johnson kj. incidence of childhood and adolescent melanoma in the united states: 19732009. pediatrics. 2013;131(5):846-854. 2. cokkinides v, weinstock m, glanz k, albano j, ward e, thun m. trends in sunburns, sun protection practices, and attitudes toward sun exposure protection and tanning among us adolescents, 1998-2004. pediatrics. 2006;118(3):853-864. mailto:lgeller.md@gmail.com skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 417 3. jones se, saraiya m. sunscreen use among us high school students, 1999-2003. the journal of school health. 2006;76(4):150-153. 4. buller db, cokkinides v, hall hi, et al. prevalence of sunburn, sun protection, and indoor tanning behaviors among americans: review from national surveys and case studies of 3 states. journal of the american academy of dermatology. 2011;65(5 suppl 1):s114-123. 5. https://www.aad.org/media/stats/prevention-andcare/vitamin-d-and-uv-exposure. 6. guy gp, jr., berkowitz z, everett jones s, watson m, richardson lc. prevalence of indoor tanning and association with sunburn among youth in the united states. jama dermatology. 2017;153(5):387-390. 7. wright c, reeder ai, gray a, cox b. child sun protection: sun-related attitudes mediate the association between children's knowledge and behaviours. journal of paediatrics and child health. 2008;44(12):692-698. 8. dusza sw, halpern ac, satagopan jm, et al. prospective study of sunburn and sun behavior patterns during adolescence. pediatrics. 2012;129(2):309-317. 9. mcree al, mays d, kornides ml, gilkey mb. counseling about skin cancer prevention among adolescents: what do parents receive from health care providers? the journal of adolescent health : official publication of the society for adolescent medicine. 2017;61(4):533-536. 10. kelly s, miller le, ahn hy, haley je. perceptions and portrayals of skin cancer among cultural subgroups. isrn dermatology. 2014;2014:325281. https://www.aad.org/media/stats/prevention-and-care/vitamin-d-and-uv-exposure https://www.aad.org/media/stats/prevention-and-care/vitamin-d-and-uv-exposure skin may 2018 volume 2 issue 3 copyright 2018 the national society for cutaneous medicine 191 pearls from the practitioner capsule commentaries: selected oral antifungal drug-drug interactions with itraconazole and terbinafine james q del rosso, do a,b,c a adjunct clinical professor (dermatology), touro university nevada, henderson, nv b research director, jdr dermatology research las vegas, nv c dermatology and cutaneous surgery, thomas dermatology, las vegas, nv terbinafine and itraconazole are oral antifungal agents utilized in dermatology to treat a variety of superficial mycotic infections. itraconazole is associated with a long list of potential drug-drug interactions, and terbinafine with a shorter list; importantly, both may induce clinically significant interactions when administered concurrently with certain drugs. 1,2 a complete review of drug-drug interactions is beyond the scope of this review, which serves as a capsule summary of three selected drug-drug interactions with itraconazole or terbinafine, with commentary suggestions on management. statins. three commonly used “statins”(simvastatin, atorvastatin, lovastatin) used to treat hyperlipidemia are metabolized by hepatic cytochrome p450 (cyp) 3a4. 3 potent inhibitors of cyp 3a4, such as itraconazole, ketoconazole, posaconazole, and erythromycin can induce muscle cramping, and in some cases rhabdomyolysis, by decreasing the metabolic clearance of these “statin” agents which causes higher serum levels; multiple cases of myopathy related to such interactions have been reported. 1-4 commentary: if antifungal therapy is needed in a patient using a statin metabolized by cyp3a4, potential options are (1) topical antifungal therapy if appropriate for the infection being treated (2) use of a non-cyp3a4-inhibiting antifungal agent such as terbinafine or (3) temporary discontinuation of the statin therapy with the approval of the prescribing clinician. 1 abstract this article provides a review of selected drug-drug interactions with itraconazole and terbinafine that are clinically relevant with potential for toxicity. these include itraconazole and certain statin agents, itraconazole and digoxin, and terbinafine and some antidepressants, with commentary suggestions on management. introduction itraconazole skin may 2018 volume 2 issue 3 copyright 2018 the national society for cutaneous medicine 192 digoxin. itraconazole has been shown to reduce the tubular renal excretion of digoxin, reported to be related to inhibition of pglycoprotein; digoxin toxicity associated with this interaction has been reported. 5-8 one study demonstrated that itraconazole produced a 56% increase in serum digoxin levels as compared to placebo. 5 commentary: as digoxin exhibits a narrow therapeuticsafety index, an alternative approach to antifungal therapy is suggested to avoid this interaction. antidepressants. terbinafine is an inhibitor of hepatic cyp 2d6, which has been shown to markedly increase serum levels of tricyclic antidepressants (eg nortriptyline, amitriptyline, imipramine) metabolized by cyp 2d6; toxicity has been reported with these interactions, presenting as ataxia, fatigue, dizziness/vertigo, appetite loss, and difficulty swallowing. 8-10 some selective serotonin reuptake inhibitors (eg paroxetine, fluoxetine) are metabolized by cyp 2d6; terbinafine has been shown to increase peak serum levels through inhibition of paroxetine metabolism. 11 commentary: when oral antifungal therapy is needed in a patient on an antidepressant that is metabolized by cyp 2d6, an alternative approach to antifungal therapy that is also expected to be effective and devoid of drugdrug interactions appears to be a prudent approach. conflict of interest disclosures: dr. del rosso is a consultant, investigator, and/or speaker for allergan, aqua/almirall, bayer, biopharmx, celgene, cipher (innocutis), cutanea, dermira, ferndale, foamix, galderma, genentech, innovaderm, leopharma, novan, pfizer (anacor), pharmaderm, promius, regeneron, sanofi/genzyme, sebacia, sunpharma, taro, unilever, valeant (ortho dermatologics), and viamet. this article was developed and written solely by the author. the author did not receive any form of compensation, either directly or indirectly, from any company or agency related to the development, authorship, or publication of this article. funding: none corresponding author: james q. del rosso, do jdr dermatology research 9080 west post road suite 100 las vegas, nevada 89148 702-331-4123 jqdelrosso@yahoo.com references: 1. katz hi, gupta ak. oral antifungal drug interactions: a mechanistic approach to understanding their cause. dermatol clin. 2003 jul;21(3):543-563. 2. shear n, drake l, gupta ak, et al. the implications and management of drug interactions with itraconazole, fluconazole and terbinafine. dermatology. 2000;201(3):196-203. 3. dybro am, damkier p, rasmussen tb, et al. statin-associated rhabdomyolysis triggered by drug-drug interaction with itraconazole. bmj case rep. 2016 sep 7;2016. pii: bcr2016216457. 4. tatro ds. drug interactions facts, wolters kluwer health inc, st. louis, missouri, usa, 2005, p 718. terbinafine skin may 2018 volume 2 issue 3 copyright 2018 the national society for cutaneous medicine 193 5. alderman cp, allcroft pd. digoxinitraconazole interaction: possible mechanisms. ann pharmacother. 1997;31(4):438-440. 6. angirasa ak, koch az. p-glycoprotein as the mediator of itraconazole-digoxin interaction. j am podiatr med assoc. 2002;92(8):471-472. 7. jalava km, partanen j, neuvonen pj. itraconazole decreases renal clearance of digoxin. ther drug monit. 1997 dec;19(6):609-13. 8. van der kuy ph, van den heuvel ha, kempen rw, et al. pharmacokinetic interaction between nortriptyline and terbinafine. ann pharmacother. 2002;36(11):1712-1714. 9. castberg i, helle j, aamo to. prolonged pharmacokinetic drug interaction between terbinafine and amitriptyline. ther drug monit. 2005 oct;27(5):680-2. 10. 4 tatro ds. drug interactions facts, wolters kluwer health inc, st. louis, missouri, usa, 2005, p 1507. 11. yasui-furukori n, saito m, inoue y, et al. terbinafine increases the plasma concentration of paroxetine after a single oral administration of paroxetine in healthy subjects. eur j clin pharmacol. 2007;63(1):5156. synopsis conclusions bimekizumab demonstrated greater skin clearance that was durable in patients with moderate to severe plaque psoriasis as compared with ustekinumab, regardless of patient subgroup. these results support bimekizumab as a psoriasis treatment suitable for a wide variety of patients given its consistent efficacy across all subgroups analyzed. objective to assess the efficacy of bimekizumab compared with ustekinumab over 52 weeks of treatment across demographic, disease characteristic, and prior treatment history subgroups of patients with moderate to severe plaque psoriasis from the be vivid study. background • bimekizumab is a monoclonal igg1 antibody that selectively inhibits il-17f in addition to il-17a, both of which play a pivotal role in the pathogenesis of psoriasis (pso).1–4 • given that the severity of pso can vary with age, weight and prior treatment exposure,5 there is a need for therapies that provide consistent and durable skin clearance, regardless of patient/disease characteristics and treatment history. methods • in be vivid (nct03370133), patients were randomized to receive bimekizumab through week 52, ustekinumab through week 52, or placebo to week 16 followed by bimekizumab (patients randomized to placebo were not included in these analyses; figure 1). • subgroup analyses were conducted based on patient demographics, disease characteristics, and prior treatment exposure. • proportions of bimekizumabversus ustekinumab-treated patients achieving 90% and 100% improvement from baseline psoriasis area and severity index (pasi 90 and pasi 100) were calculated at weeks 16 and 52. missing data were imputed as non-response (nri). results patient population • baseline characteristics for patients randomized to bimekizumab or ustekinumab are shown in table 1. bimekizumab efficacy across subgroups • pasi 90 (figure 2) and pasi 100 (figure 3) response rates were greater in patients randomized to bimekizumab compared with ustekinumab across all subgroups at week 16. • responses were further improved or maintained in bimekizumab-treated patients through week 52 and remained higher than responses in patients receiving ustekinumab (figure 2 and figure 3). b. strober,1,2 j.g. krueger,3 n. magnolo,4 r. vender,5 d.p. toth,6 d. thaçi,7 m. wang,8 c. cioffi,8 c. madden,8 r.b. warren9 bsa: body surface area; dlqi: dermatology life quality index; iga: investigator’s global assessment; il: interleukin; imp: investigational medicinal product; itt: intention-to-treat; nri: non-responder imputation; pasi: psoriasis area and severity index; q4w: every 4 weeks; q12w: every 12 weeks; sd: standard deviation; tnf: tumor necrosis factor. figure 1 study design bimekizumab 320 mg q4w (n=321) ustekinumab 45/90 mg q12wb (n=163) age (years), mean ± sd 45.2 ± 14.0 46.0 ± 13.6 <40 years, n (%) 123 (38.3) 57 (35.0) 40–<65 years, n (%) 164 (51.1) 88 (54.0) ≥65 years, n (%) 34 (10.6) 18 (11.0) male, n (%) 229 (71.3) 117 (71.8) caucasian, n (%) 237 (73.8) 120 (73.6) weight (kg), mean ± sd 88.7 ± 23.1 87.2 ± 21.1 ≤100 kg, n (%) 226 (70.4) 122 (74.8) >100 kg, n (%) 95 (29.6) 41 (25.2) duration of psoriasis (years), mean ± sd 16.0 ± 11.6 17.8 ± 11.6 <median (14.54 years), n (%) 169 (52.6) 73 (44.8) ≥median (14.54 years), n (%) 152 (47.4) 90 (55.2) pasi, mean ± sd 22.0 ± 8.6 21.3 ± 8.3 pasi<20, n (%) 170 (53.0) 102 (62.6) pasi≥20, n (%) 151 (47.0) 60 (36.8) bsa (%), mean ± sd 29.0 ± 17.1 27.3 ± 16.7 igac, n (%) 3: moderate 201 (62.6) 96 (58.9) 4: severe 119 (37.1) 66 (40.5) dlqi total, mean ± sd 9.9 ± 6.3 11.0 ± 6.9 prior biologic therapy, n (%) 125 (38.9) 63 (38.7) anti-tnf 51 (15.9) 24 (14.7) anti-il-17 76 (23.7) 38 (23.3) anti-il-23 16 (5.0) 6 (3.7) institutions: 1yale university, new haven, ct, usa; 2central connecticut dermatology research, cromwell, ct, usa; 3the rockefeller university, new york, ny, usa; 4universitätsklinikum münster, münster, germany; 5mcmaster university, hamilton, on, canada; 6probity medical research; windsor, on, canada; 7institute and comprehensive center for inflammation medicine, university hospital of lübeck, lübeck, germany; 8ucb pharma, raleigh, nc, usa; 9dermatology centre, salford royal nhs foundation trust, manchester nihr biomedical research centre, the university of manchester, manchester, uk. bimekizumab versus ustekinumab efficacy across subgroups of patients with moderate to severe plaque psoriasis: results from the multicenter, randomized, double-blinded phase 3 be vivid trial presented at winter clinical 2021 virtual congress | january 16–24 references: 1durham l. curr rheumatol reports 2015;17:55; 2fujishima s. arch dermatol res 2010;302:499–505; 3glatt s. br j clin pharmacol 2017;83:991–1001; 4papp ka. j am acad dermatol 2018;79:277–86.e10; 5kamiya k. int j mol sci 2019;20:4347. author contributions: substantial contributions to study conception/design, or acquisition/analysis/interpretation of data: bs, jgk, nm, rv, dpt, dt, mw, cc, cm, rbw; drafting of the publication, or revising it critically for important intellectual content: bs, jgk, nm, rv, dpt, dt, mw, cc, cm, rbw; final approval of the publication: bs, jgk, nm, rv, dpt, dt, mw, cc, cm, rbw. author disclosures: bs: consultant (honoraria) from abbvie, almirall, amgen, arcutis, arena, aristea, boehringer ingelheim, bristol myers squibb, celgene, dermavant, dermira, eli lilly, equillium, gsk, janssen, leo pharma, meiji seika pharma, mindera, novartis, ortho dermatologics, pfizer, regeneron, sanofi-genzyme, sun pharma and ucb pharma; speaker for abbvie, amgen, eli lilly, janssen and ortho dermatologics; scientific director (consulting fee) for corrona psoriasis registry; investigator for abbvie, cara, corrona psoriasis registry, dermavant, dermira and novartis; editor-in-chief (honorarium) for journal of psoriasis and psoriatic arthritis; jgk: grants paid to institution from abbvie, akros, allergan, amgen, avillion, biogen ma, boehringer ingelheim, botanix, bristol myers squibb, celgene, eli lilly, exicure, incyte, innovaderm, janssen, leo pharma, novan, novartis, paraxel, pfizer, regeneron, sienna, ucb pharma and vitae; personal fees from abbvie, allergan, almirall, amgen, arena, aristea, asana, aurigne, biogen, boehringer ingelheim, bristol myers squibb, celgene, eli lilly, escalier, leo pharma, nimbus, novartis, menlo, pfizer, sanofi, sienna, sun pharma, ucb pharma and valeant; nm: honoraria, advisor, and/or paid speaker for and/or participated as principal investigator in clinical trials for abbvie, almirall, asana, biogen, bristol myers squibb, boehringer ingelheim, celgene corporation, dermira, dr. reddy’s laboratories, eli lilly, galderma, genentech, incyte, janssen-cilag, kyowa kirin, leo pharma, merck, novartis, pfizer, regeneron, sun pharma and ucb pharma; rv: consultant, and/or scientific advisor, and/or investigator, and/or speaker for abbvie, amgen, astellas, bausch health/valeant, boehringer ingelheim, bristol myers squibb, celgene, dermira, eli lilly, galderma, gsk, janssen, leo pharma, merck (msd), merck serono, novartis, pfizer, regeneron, roche, sanofi-aventis/genzyme, sun pharma, takeda and ucb pharma; dpt: investigator and/or speaker for abbvie, amgen, arcutis, avillion, bausch health, bristol myers squibb, boehringer ingelheim, celgene, dermira, eli lilly, galderma, gsk, incyte, janssen, leo pharma, merck-serono, novartis, pfizer, regeneron, sanofi-aventis/genzyme, sun pharma and ucb pharma; dt: honoraria for participation on advisory boards, as a speaker and for consultancy from abbvie, almirall, amgen, biogen-idec, boehringer ingelheim, bristol myers squibb, celgene, ds-biopharma, eli lilly, galapagos, janssen, leo pharma, morphosis, novartis, pfizer, regeneron, samsung, sandoz-hexal, sanofi and ucb pharma; research grants received from celgene and novartis; mw: employee of ucb pharma; cc, cm: employees and shareholders of ucb pharma; rbw: research grants from abbvie, almirall, amgen, celgene, eli lilly, janssen, leo pharma, novartis, pfizer and ucb pharma; consultant for abbvie, almirall, amgen, arena, avillion, bristol myers squibb, boehringer ingelheim, celgene, eli lilly, janssen, leo pharma, novartis, pfizer, sanofi and ucb pharma. acknowledgements: this study was funded by ucb pharma. we would like to thank the patients and their caregivers in addition to all the investigators and their teams who contributed to this study. the authors acknowledge mylene serna, pharmd, ucb pharma, smyrna, ga, usa and susanne wiegratz, msc, ucb pharma, monheim am rhein, germany for publication coordination; eva cullen, phd, ucb pharma, brussels, belgium for critical review; kristian clausen, mph, costello medical, cambridge, uk for medical writing and editorial assistance; and the costello medical design team for design support. all costs associated with development of this presentation were funded by ucb pharma. previously presented at eadv 2020 virtual congress | october 29–31 arandomization was stratified by prior biologic exposure and region; bpatients randomized to placebo were not included in these analyses; custekinumab dosing was based on weight: patients ≤100 kg at baseline received one ustekinumab 45 mg injection and one placebo injection; patients >100 kg at baseline received two ustekinumab 45 mg injections (90 mg total). table 1 baseline characteristicsa apatients randomized to placebo are not shown here; bustekinumab dosing was based on weight: patients ≤100 kg at baseline received one ustekinumab 45 mg injection and one placebo injection, patients >100 kg at baseline received two ustekinumab 45 mg injections (90 mg total); cin each treatment group, one patient with iga=2 was mistakenly enrolled. figure 2 achievement of pasi 90 at weeks 16 and 52 (itt, nri) a) week 16 bimekizumab demonstrated greater skin clearance vs ustekinumab, regardless of patient subgroup. bimekizumab vs subgroup analyses: figure 3 achievement of pasi 100 at weeks 16 and 52 (itt, nri) b) week 52 ain each treatment group, one patient with iga=2 was mistakenly enrolled and is not shown here. a) week 16 b) week 52 ain each treatment group, one patient with iga=2 was mistakenly enrolled and is not shown here. disease characteristics • duration (<median, ≥median) • severity (pasi<20, pasi≥20; iga=3, iga=4) prior treatment exposure • prior biologic exposure (yes, no) • prior anti-tnf exposure (yes, no) • prior anti-il-17 exposure (yes, no) patient demographics • age (<40, 40–<65, ≥65 years) • weight (≤100, >100 kg) bimekizumab ustekinumab bimekizumab 81.9% ustekinumab 55.8% age (years) ≥65 baseline weight (kg) 40–<65 <40 ≤100 >100 psoriasis disease duration <median [14.54 years] ≥median [14.54 years] baseline disease severity pasi <20 pasi ≥20 baseline igaa 3 4 prior biologic exposure yes no prior anti-tnf exposure yes no prior anti-il-17 exposure yes no % of patients 80604020 1000 ustekinumab n/n 37/57 79/139 12/24 59/100 32/63 33/66 58/96 34/60 57/102 46/90 45/73 23/41 68/122 45/88 9/18 21/38 70/125 % 64.9% 56.8% 50.0% 59.0% 50.8% 50.0% 60.4% 56.7% 55.9% 51.1% 61.6% 56.1% 55.7% 51.1% 50.0% 55.3% 56.0% bimekizumab n/n 98/123 223/270 39/51 155/196 107/125 95/119 166/201 126/151 136/170 130/152 132/169 78/95 184/226 134/164 30/34 66/76 196/245 % 79.7% 82.6% 76.5% 79.1% 85.6% 79.8% 82.6% 83.4% 80.0% 85.5% 78.1% 82.1% 81.4% 81.7% 88.2% 86.8% 80.0% 10 30 50 70 90 bimekizumab 58.6% ustekinumab 20.9% age (years) ≥65 baseline weight (kg) 40–<65 <40 ≤100 >100 psoriasis disease duration <median [14.54 years] ≥median [14.54 years] baseline disease severity pasi <20 pasi ≥20 baseline igaa 3 4 prior biologic exposure yes no prior anti-tnf exposure yes no prior anti-il-17 exposure yes no % of patients 80604020 1000 ustekinumab n/n 13/57 27/139 7/24 20/100 14/63 12/66 22/96 15/60 19/102 17/90 17/73 6/41 28/122 19/88 2/18 8/38 26/125 % 22.8% 19.4% 29.2% 20.0% 22.2% 18.2% 22.9% 25.0% 18.6% 18.9% 23.3% 14.6% 23.0% 21.6% 11.1% 21.1% 20.8% bimekizumab n/n 77/123 158/270 30/51 112/196 76/125 67/119 120/201 96/151 92/170 82/152 106/169 52/95 136/226 96/164 15/34 45/76 143/245 % 62.6% 58.5% 58.8% 57.1% 60.8% 56.3% 59.7% 63.6% 54.1% 53.9% 62.7% 54.7% 60.2% 58.5% 44.1% 59.2% 58.4% 10 30 50 70 90 bimekizumab 64.5% ustekinumab 38.0% age (years) ≥65 baseline weight (kg) 40–<65 <40 ≤100 >100 psoriasis disease duration <median [14.54 years] ≥median [14.54 years] baseline disease severity pasi <20 pasi ≥20 baseline igaa 3 4 prior biologic exposure yes no prior anti-tnf exposure yes no prior anti-il-17 exposure yes no % of patients 80604020 1000 ustekinumab n/n 29/57 53/139 9/24 37/100 25/63 20/66 42/96 24/60 38/102 28/90 34/73 15/41 47/122 29/88 4/18 17/38 45/125 % 50.9% 38.1% 37.5% 37.0% 39.7% 30.3% 43.8% 40.0% 37.3% 31.1% 46.6% 36.6% 38.5% 33.0% 22.2% 44.7% 36.0% bimekizumab n/n 85/123 177/270 29/51 123/196 83/125 73/119 133/201 98/151 108/170 99/152 107/169 63/95 143/226 103/164 18/34 52/76 154/245 % 69.1% 65.6% 56.9% 62.8% 66.4% 61.3% 66.2% 64.9% 63.5% 65.1% 63.3% 66.3% 63.3% 62.8% 52.9% 68.4% 62.9% 10 30 50 70 90 age (years) ≥65 baseline weight (kg) 40–<65 <40 ≤100 >100 psoriasis disease duration <median [14.54 years] ≥median [14.54 years] baseline disease severity pasi <20 pasi ≥20 baseline igaa 3 4 prior biologic exposure yes no prior anti-tnf exposure yes no prior anti-il-17 exposure yes no % of patients 80604020 1000 ustekinumab n/n 34/57 69/139 12/24 54/100 27/63 33/66 48/96 34/60 47/102 43/90 38/73 21/41 60/122 39/88 8/18 15/38 66/125 % 59.6% 49.6% 50.0% 54.0% 42.9% 50.0% 50.0% 56.7% 46.1% 47.8% 52.1% 51.2% 49.2% 44.3% 44.4% 39.5% 52.8% bimekizumab n/n 109/123 230/270 43/51 167/196 106/125 100/119 172/201 138/151 135/170 128/152 145/169 79/95 194/226 139/164 25/34 63/76 210/245 % 88.6% 85.2% 84.3% 85.2% 84.8% 84.0% 85.6% 91.4% 79.4% 84.2% 85.8% 83.2% 85.8% 84.8% 73.5% 82.9% 85.7% 10 30 50 70 90 bimekizumab 85.0% ustekinumab 49.7% screening initial treatment period maintenance periodscreening open-label extension study: be bright (nct03598790) 20 weeks after last dose of imp: safety follow-up week 16 week 24baseline 2–5 weeks bimekizumab 320 mg q4w placebob ustekinumab 45/90 mg q12wc bimekizumab 320 mg q4w week 52 n=321 n=83 n=163 active comparator period patient inclusion criteria moderate to severe disease: pasi ≥12, bsa a�ected by psoriasis ≥10% and iga score ≥3 ≥18 years of age  plaque psoriasis with ≥6 months’ symptom duration n=567 4:1:2 randomizationa skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 83 clinical management recommendation considerations in the management of actinic keratosis: the importance of adherence and persistence to therapy justin w. marson, md1, james q. del rosso, do2, neal bhatia, md3, darrell s. rigel, md, ms4 1national society for cutaneous medicine, new york, ny 2jdr dermatology research/thomas dermatology, las vegas, nv 3director of clinical dermatology, therapeutics clinical research, san diego, ca 4department of dermatology, nyu grossman school of medicine, new york, ny adherence can defined as how closely a patient follows and executes a prescribed treatment regimen.1,2 this includes (but is not limited to) factors such as obtaining the medication, completing the entirety of a treatment course (persistence), utilizing the medication at the appropriate frequency and dose, and properly implementing the route/location of administration.1-4 even after successfully obtaining a medication, adherence can be compromised by the abstract background: actinic keratosis (ak) is a pre-malignant lesion with a poorly defined risk of progression to invasive squamous cell carcinoma (scc). aks are also associated with increased future risk of invasive scc. however, there are many barriers to therapy adherence that may affect long-term treatment efficacy. objective: to review the current literature reporting known known factors of ak treatment nonadherence intrinsic to patient behavior and treatment regimens and re-examine how dermatologists can navigate these challenges. methods: a medline literature search was performed to identify existing evidence regarding barriers to adherence with ak treatment regimens intrinsic to patient behavior, patient counseling, and treatment regimens pertinent for review. results & discussion: factors intrinsic to prescribed patient-applied therapy that can exacerbate non-adherence include: 1) length of treatment duration, 2) frequency of application, 3) complexity of treatment regimen, 4) duration and 5) severity of local skin reactions (lsr) and adverse reactions. novel mechanisms of action that induce cellular apoptosis (as opposed to necrosis) via inhibition of tubulin polymerization and cell cycle arrest, may promote treatment regimen adherence and long-term outcomes. dermatologists should also be conscious of how they counsel patients as insufficient counseling may also lead to poor adherence. conclusion: dermatologists must understand the value of shorter course therapies and their positive impact on adherence and be well-versed in the mechanisms, efficacy and adverse events associated with treatment options. by doing so, dermatologists may best counsel and educate patients and devise regimens that address individualized patient concerns. introduction skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 84 length of treatment, the complexity of a regimen, perceived (relative) lack of improvement, as well as duration and severity of adverse events, such as local skin reactions.3,4 unfortunately, in a realworld setting, a patient’s adherence to therapy is as important, if not more so, than the efficacy and mechanism of action of the chosen regimen in achieving optimal longterm outcomes. these barriers can be amplified when managing chronic dermatoses as patients must adhere to repeated, regular treatments over the course of months or years. furthermore, future repeat cycles of therapy may be negatively impacted by current severe local skin reactions. these negative experiences may color patients’ perceptions of ak management and affect their risk-benefit analyses future therapy. actinic keratoses (ak) are likely one of the most prevalent skin diseases treated by dermatologists, accounting for over 14% of all dermatology visits and upwards of $3.1 billion in annual healthcare expenditures.5,6 these pre-malignant lesions arise from decades of actinic and ultraviolet damage leading to field cancerization. the presence of a single ak therefore likely suggests the presence of many subclinical actinic keratoses in evolution. aks are also known to have the potential to progress into invasive cutaneous squamous cell carcinoma (cscc).7-11 unfortunately, there are no universally accepted clinical factors and few histopathological signs to indicate which ak has the 0.025-16%12 risk of progression to invasive scc and therefore all aks require medical evaluation and management. because of the chronic nature of ak pathophysiology as well as the need for their treatment, long-term efficacy of therapy relies not only on mechanism of action but also the adherence to the prescribed treatment regimen. a review of the literature pertaining to the epidemiology, natural history, prognosis, management of ak as well as the mechanism of action of and adherence to current and impending patient-applied ak therapy was conducted. the goal of this search was to evaluate the literature for barriers to adherence intrinsic to patient behavior, patient counseling, and treatment regimens. the medline database was queried for all relevant articles published between 1980 and 2021 using exploded mesh terms and keywords pertaining to the following themes: diagnosis, prognosis, and epidemiology, risk factors, squamous cell carcinoma, therapy. the boolean term “and” was used to find the intersection of these themes with the term “actinic keratosis.” the state of patient-applied field therapy for actinic keratoses aside from prevention and sun-protective measures, there are two overarching principles for treating aks: lesion-directed therapy and field therapy.13 lesion-directed therapy are office-based, dermatologistadministered treatments such as cryosurgery, surgery, chemical peel, or laser that primarily target single, clinically visible aks.14,15 these treatments are often complemented and augmented by field therapy such as photodynamic therapy (pdt) or at-home, patient-applied therapies that treat both clinically-visible and subclinical aks.3,4,14-16 field therapy is important in managing aks between office visits given the likelihood of subclinical methods results & discussion skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 85 lesions in the setting of field cancerization and chronic nature of aks and actinic damage.17-20 current field-therapies rely on either disrupting cell signaling, halting cellular division or stimulating the immune system to detect and destroy atypical cells.21 while there are multiple pathways that these therapies utilize, they function by either primarily or secondarily stimulating local (and in the case of imiquimod, also systemic) inflammation.14,21 agents such as 5-fluorouracil(5-fu), which interferes with dna replication, applied over 2-6 weeks, can induce significant inflammation, leading to cellular necrosis, to treat aks.14,22,23 in a less severe fashion, imiquimod, which augments the immune system to induce inflammation, applied over 4-16 weeks, can lead to a less robust inflammatory response that also utilizes necrosis in subacute and chronic ak management.14,22,23 however, these mechanisms that utilize necrosis can induce moderate to severe local skin reactions (lsr), including varying degrees of painful erythema, crusting, and erosions in up to 90% of patients that may last several weeks.3,24,25 conversely, agents that are thought to treat aks by promoting apoptosis, such as diclofenac (which inhibits epidermal cox-2 expression) lead to negligible lsrs, with the caveat that treatment requires 60-90 days of continual twice daily application.3,22,26,27 barriers to effective field therapy for ak while there are few head-to-head definitive trials to assess the relative (real-world) efficacy of various field therapies, recent meta-analyses have suggested there is a hierarchy of ak treatment efficacy.3,14,22 therapeutic agents that induce more inflammation (and lsrs) tend to have greater efficacy. unfortunately, prior studies have also demonstrated that patients are more than willing to tolerate increased risk of developing skin cancer and potential improvements in the appearance of their skin if it means minimizing the inconvenience of treatment by reducing the 1) severity of local skin reactions, 2) length/frequency of treatment, and 3) eliminating systemic symptoms.28 given current available patient-applied home therapies, selecting an optimal agent requires balancing ideal efficacy with potential patient non-adherence with treatment application. figure 1. apoptosis versus necrosis. agents such as diclofenac and tirbanibulin induce apoptosis which minimize inflammation and local skin reactions relative to necrosis-induced inflammation from 5fluorouracil or ingenol mebutate. skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 86 choosing a regimen is further complicated when considering the chronic nature of actinic damage and aks. given the accumulated chronic actinic damage will only produce more aks (and other skin cancers) with time demanding prolonged recurrent (and necessary) treatment, dermatologists must also consider how a patient’s experience with treatment will affect their adherence to future therapies, and therefore the overall, long-term outcomes associated with each regimen. advancements in patient-applied treatment for actinic keratoses studies suggest that shorter course therapies16 that are less cumbersome29 may be more practical for patients and result in improved adherence, and therefore, improved real-world efficacy. studies have attempted to combine available therapies in hopes of synergistically improving efficacy and reducing duration/frequency of application.30 however, combinations such as 5-fu and calcipotriene, though potentially more efficacious than 5-fu alone based on the limited data available, also lead to increased rates of intolerable, dose-limiting lsrs.30 figure 2. tirbanibulin’s mechanism of action. microtubule polymerization requires α-tubulin and ꞵtubulin dimerization. tirbanibulin inhibits tubulin dimerization thereby leading to cell-cycle arrest and apoptosis. advances in our understanding of keratinocyte dysplasia have yielded new small molecules capable of inducing apoptosis with minimal inflammation.31,32 in vitro studies have demonstrated that kx2391 (tirbanibulin) specifically targets rapidly dividing cells and, by reversible-binding of microtubules essential to cellular division, prevents polymerization of tubulin thereby leading to cell-cycle arrest and apoptosis.31,32 tirbanibulin may also exert anti-tumor activity by disrupting a nonreceptor tyrosine kinase, the protooncogene src kinase.31 clinical trials have shown after only 5 consecutive days of daily tirbanibulin application to the face and scalp, participants noticed continued ak clearance through day 57 with 40-50% with 100% clearance.33-35 at 12-month follow up, not only were there no notable adverse effects, but 42% of participants had no recurrence of originally treated aks.34,35 perhaps more importantly from an adherence standpoint, studies have shown that lsrs were mildmoderate, peaked within 8 days of first application and resolved entirely within 1529 days.33-35 taken together these data suggest inhibition of tubulin polymerization provides an efficacious way to treat aks that also mitigates unpleasant adverse effects of contemporary ak treatments and its shorter course may also further improve adherence to therapy. the importance of actinic keratosis therapy and patient counseling studies have also demonstrated the importance of the semantics and wording used during patient counseling had a significant effect in patients’ decision-making regarding ak treatment.36 a significantly larger proportion of participants opted for treatment when told “aks are precancers” or had the potential for malignant skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 87 transformation compared to when were more optimistically counseled by highlighting the chance of regression.36 more recent meta-analyses of field therapies have determined there may in fact be a hierarchy of efficacy.3,14 it is important that physicians are aware of both the efficacy of treatment and severity of local skin reactions and other adverse events so that they can provide focused counseling for patients. dermatologists may consider off-label modifications and adjunctive therapies (such as steroidal and non-steroidal antiinflammatory agents, moisturizers and emollients, topical antibiotics, and antipruritic agents) to mitigate lsrs with the caveat that there is limited evidence for their use.37 by being able to combine evidencedbased regimens with patient-centered values, dermatologists may potentially maximize long-term compliance and therefore achieve (near-)ideal outcomes regarding ak care.38 aks are a chronic condition with a still poorly defined potential for progression into invasive scc. because of the overall chronic nature of aks and actinic damage, adequate treatment requires a combination of recurrent dermatologist-administered office treatment and continual patientapplied home therapies. to achieve ideal outcomes, dermatologists must understand the value of shorter course therapies and their positive impact on adherence and be well-versed in the mechanisms, efficacy and adverse events associated with treatment options so they may best counsel and educate patients as well as devise regimens that address individualized patient concerns. in this way, dermatologists can potentially maximize adherence to therapy and improve long-term patient outcomes. conflict of interest disclosures: jwm has no relevant disclosures. jdr serves as a research investigator, speaker, and consultant for almirall, bausch health (ortho dermatology), and sun pharma and a consultant for biofrontera. nb has affiliations with abbvie, almirall, biofrontera, bms, bi, epi health, ferndale, foamix, galderma, incyte, isdin, j&j, laroche-posay, leo, lilly, ortho, pfizer, p&g, regeneron, sanofi, sunpharma, vyne, and vyome. dsr served as an advisory board member for almirall, inc. funding: this study received funding from an unrestricted educational grant from almirall, inc. corresponding author: justin w. marson, md 35 e 35th st. #208 new york ny, 10016 email: justin.w.marson@gmail.com references: 1. r ahn cs, culp l, huang ww, davis sa, feldman sr. adherence in dermatology. j dermatolog treat. 2017 mar;28(2):94-103. doi: 10.1080/09546634.2016.1181256. epub 2016 may 15. pmid: 27180785. 2. lee ia, maibach hi. pharmionics in dermatology: a review of topical medication adherence. am j clin dermatol. 2006;7(4):231-6. doi: 10.2165/00128071-200607040-00004. pmid: 16901183. 3. neri l, peris k, longo c, calvieri s, frascione p, parodi a, eibenschuz l, bottoni u, pellacani g; actinic keratosis treatment adherence initiative (ak-train) study group. physicianpatient communication and patient-reported outcomes in the actinic keratosis treatment adherence initiative (ak-train): a multicenter, prospective, real-life study of treatment satisfaction, quality of life and adherence to topical field-directed therapy for the treatment of actinic keratosis in italy. j eur acad dermatol venereol. 2019 jan;33(1):93-107. doi: 10.1111/jdv.15142. epub 2018 jul 8. pmid: 29920789. 4. kopasker, d., kwiatkowski, a., matin, r.n., harwood, c.a., ismail, f., lear, j.t., thomson, j., hasan, z., wali, g.n., milligan, a., crawford, l., ahmed, i., duffy, h., proby, c.m., allanson, p.f., 2019. patient preferences for topical treatment of actinic keratoses: a discrete‐choice experiment. british journal of dermatology 180, 902–909.. doi:10.1111/bjd.16801 conclusion mailto:justin.w.marson@gmail.com skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 88 5. bickers dr, lim hw, margolis d, weinstock ma, goodman c, faulkner e, gould c, gemmen e, dall t; american academy of dermatology association; society for investigative dermatology. the burden of skin diseases: 2004 a joint project of the american academy of dermatology association and the society for investigative dermatology. j am acad dermatol. 2006 sep;55(3):490-500. doi: 10.1016/j.jaad.2006.05.048. pmid: 16908356. 6. yeung h, baranowski ml, swerlick ra, chen sc, hemingway j, hughes dr, duszak r jr. use and cost of actinic keratosis destruction in the medicare part b fee-for-service population, 2007 to 2015. jama dermatol. 2018 nov 1;154(11):1281-1285. doi: 10.1001/jamadermatol.2018.3086. pmid: 30326488; pmcid: pmc6248125. 7. filosa a, filosa g. actinic keratosis and squamous cell carcinoma: clinical and pathological features. g ital dermatol venereol. 2015;150(4):379-84. 8. marks r, foley p, goodman g, hage bh, selwood ts. spontaneous remission of solar keratoses: the case for conservative management . br j dermatol. 1986;115:649655. 9. marks r, rennie g, selwood ts. malignant transformation of solar keratoses to squamous cell carcinoma . lancet . 1988;1:795-797. 10. dodson jm, despain j, hewett je, clark dp. malignant potential of actinic keratoses and the controversy over treatment. a patient-oriented perspective. arch dermatol. 1991 jul;127(7):1029-31. pmid: 2064402. 11. marks r. the role of treatment of actinic keratoses in the prevention of morbidity and mortality due to squamous cell carcinoma. arch dermatol. 1991 jul;127(7):1031-3. pmid: 2064403. 12. glogau rg. the risk of progression to invasive disease. j am acad dermatol. 2000;42(1 pt 2):23-4. 13. de oliveira ecv, da motta vrv, pantoja pc, ilha cso, magalhães rf, galadari h, leonardi gr. actinic keratosis review for clinical practice. int j dermatol. 2019 apr;58(4):400-407. doi: 10.1111/ijd.14147. epub 2018 aug 2. pmid: 30070357. 14. jansen mhe, kessels jphm, nelemans pj, kouloubis n, arits ahmm, van pelt hpa, quaedvlieg pjf, essers bab, steijlen pm, kelleners-smeets nwj, mosterd k. randomized trial of four treatment approaches for actinic keratosis. n engl j med. 2019 mar 7;380(10):935-946. doi: 10.1056/nejmoa1811850. pmid: 30855743. 15. dianzani c, conforti c, giuffrida r, corneli p, di meo n, farinazzo e, moret a, magaton rizzi g, zalaudek i. current therapies for actinic keratosis. int j dermatol. 2020 jun;59(6):677684. doi: 10.1111/ijd.14767. epub 2020 feb 3. pmid: 32012240. 16. shergill b, zokaie s, carr aj. non-adherence to topical treatments for actinic keratosis. patient prefer adherence. 2013 dec 17;8:35-41. doi: 10.2147/ppa.s47126. pmid: 24379656; pmcid: pmc3872140. 17. guenthner st, hurwitz rm, buckel lj, gray hr. cutaneous squamous cell carcinomas consistently show histologic evidence of in situ changes: a clinicopathologic correlation. j am acad dermatol. 1999;41(3 pt 1):443-8 18. keller b, braathen lr, marti hp, hunger re. skin cancers in renal transplant recipients: a description of the renal transplant cohort in bern. swiss med wkly. 2010 jul 15;140:w13036. doi: 10.4414/smw.2010.13036. pmid: 20652847. 19. foley p, stockfleth e, peris k, basset-seguin n, cerio r, antonio sanches j, guillen c, farrington e, lebwohl m. adherence to topical therapies in actinic keratosis: a literature review. j dermatolog treat. 2016 nov;27(6):538-545. doi: 10.1080/09546634.2016.1178372. epub 2016 may 10. pmid: 27161045. 20. berker, d., mcgregor, j.m., mohd mustapa, m.f., exton, l.s., hughes, b.r., mchenry, p.m., gibbon, k., buckley, d.a., nasr, i., duarte williamson, c.e., swale, v.j., leslie, t.a., mallon, e.c., wakelin, s., ungureanu, s., hunasehally, r.y.p., cork, m., johnston, g.a., natkunarajah, j., worsnop, f.s., chiang, n., donnelly, j., saunders, c., brian, a.g., 2017. british association of dermatologists’ guidelines for the care of patients with actinic keratosis 2017. british journal of dermatology 176, 20– 43.. doi:10.1111/bjd.15107 21. berman b, cockerell cj. pathobiology of actinic keratosis: ultraviolet-dependent keratinocyte proliferation. j am acad dermatol. 2013 jan;68(1 suppl 1):s10-9. doi: 10.1016/j.jaad.2012.09.053. pmid: 23228301. 22. gupta ak, paquet m. network meta-analysis of the outcome 'participant complete clearance' in nonimmunosuppressed participants of eight interventions for actinic keratosis: a follow-up on a cochrane review. br j dermatol. 2013 aug;169(2):250-9. doi: 10.1111/bjd.12343. pmid: 23550994. skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 89 23. aad. actinic keratoses: diagnosis and treatment. 2019. https://www.aad.org/public/diseases/scalyskin/actinic-keratosis 24. cerio r. the importance of patient-centred care to overcome barriers in the management of actinic keratosis. j eur acad dermatol venereol. 2017 mar;31 suppl 2:17-20. doi: 10.1111/jdv.14091. pmid: 28263022. 25. hansen jb, larsson t, dunkelly-allen n, veverka ka, feldman sr. real-world effectiveness and safety of fieldand lesiondirected treatments for actinic keratosis. j drugs dermatol. 2020 aug 1;19(8):756-762. doi: 10.36849/jdd.2020.5123. pmid: 32804451. 26. buckman sy, gresham a, hale p, hruza g, anast j, masferrer j, pentland ap. cox-2 expression is induced by uvb exposure in human skin: implications for the development of skin cancer. carcinogenesis. 1998 may;19(5):723-9. doi: 10.1093/carcin/19.5.723. pmid: 9635856. 27. elmets, c.a., ledet, j.j., athar, m., 2014. cyclooxygenases: mediators of uv-induced skin cancer and potential targets for prevention. journal of investigative dermatology 134, 2497– 2502.. doi:10.1038/jid.2014.192 28. kopasker, d., kwiatkowski, a., matin, r.n., harwood, c.a., ismail, f., lear, j.t., thomson, j., hasan, z., wali, g.n., milligan, a., crawford, l., ahmed, i., duffy, h., proby, c.m., allanson, p.f., 2019. patient preferences for topical treatment of actinic keratoses: a discrete‐choice experiment. british journal of dermatology 180, 902–909.. doi:10.1111/bjd.16801 29. werner rn, jacobs a, rosumeck s, erdmann r, sporbeck b, nast a.methods and results report evidence and consensus-based (s3) guidelines for the treatment of actinic keratosis international leagueof dermatological societies in cooperation with the european dermatol-ogy forum.j eur acad dermatol venereol2015;29: e1–e66 30. cunningham tj, tabacchi m, eliane jp, tuchayi sm, manivasagam s, mirzaalian h, turkoz a, kopan r, schaffer a, saavedra ap, wallendorf m, cornelius la, demehri s, “randomized trial of calcipotriol combined with 5-fluorouracil for skin cancer precursor immunotherapy,” j clin invest. 2017 jan 3;127(1):106-116. doi: 10.1172/jci89820. epub 2016 nov 21. 31. smolinski, m.p., bu, y., clements, j., gelman, i.h., hegab, t., cutler, d.l., fang, j.w.s., fetterly, g., kwan, r., barnett, a., lau, j.y.n., hangauer, d.g., 2018. discovery of novel dual mechanism of action src signaling and tubulin polymerization inhibitors (kx2-391 and kx2361). journal of medicinal chemistry 61, 4704– 4719.. doi:10.1021/acs.jmedchem.8b00164 32. niu l, yang j, yan w, yu y, zheng y, ye h, chen q, chen l. reversible binding of the anticancer drug kxo1 (tirbanibulin) to the colchicine-binding site of β-tubulin explains kxo1's low clinical toxicity. j biol chem. 2019 nov 29;294(48):18099-18108. doi: 10.1074/jbc.ra119.010732. epub 2019 oct 18. pmid: 31628188; pmcid: pmc6885616. 33. blauvelt, a., kempers, s., forman, s., lain, e., & bruce, s. (2020). tirbanibulin ointment 1%, a novel inhibitor of tubulin polymerization and src kinase signaling , for the treatment of actinic keratosis (ak): results from two pivotal phase iii studies. skin the journal of cutaneous medicine, 4(5), s63. https://doi.org/10.25251/skin.4.supp.62 34. blauvelt, a., kempers, s., schlesinger, t., lain, e., wang, h., cutler, d., lebwohl, m., fang, j., & kwan, r. (2020). tirbanibulin ointment 1% for actinic keratosis (ak): pooled data from two phase 3 studies. skin the journal of cutaneous medicine, 4(6), s121. https://doi.org/10.25251/skin.4.supp.121 35. blauvelt a, kempers s, lain e, schlesinger t, tyring s, forman s, ablon g, martin g, wang h, cutler dl, fang j, kwan mr; phase 3 tirbanibulin for actinic keratosis group. phase 3 trials of tirbanibulin ointment for actinic keratosis. n engl j med. 2021 feb 11;384(6):512-520. doi: 10.1056/nejmoa2024040. pmid: 33567191. 36. berry, k., butt, m., kirby, j.s., 2017. influence of information framing on patient decisions to treat actinic keratosis. jama dermatology 153, 421.. doi:10.1001/jamadermatol.2016.5245 37. freeman, s., bettencourt, m., corliss, m., dunkellyallen, n., & veverka, k. a. (2020). evaluation of different approaches in managing local skin reactions with the use of ingenol mebutate 0.015% and 0.05% during the treatment of actinic keratosis. skin the journal of cutaneous medicine, 4(5), s65. https://doi.org/10.25251/skin.4.supp.64 38. grada, a., feldman, s.r., bragazzi, n.l., damiani, g., 2021. patient‐reported outcomes of topical therapies in actinic keratosis: a systematic review. dermatologic therapy.. doi:10.1111/dth.14833 https://www.aad.org/public/diseases/scaly-skin/actinic-keratosis https://www.aad.org/public/diseases/scaly-skin/actinic-keratosis https://doi.org/10.25251/skin.4.supp.62 https://doi.org/10.25251/skin.4.supp.121 https://doi.org/10.25251/skin.4.supp.64 powerpoint presentation providing consultancy & research in health economics field treatments for actinic keratosis: a systematic review and network meta-analysis authors: martin g1, berman b2, feldman s3, armstrong a4, edwards m5, graziadio s5, mccool r5, arber m5, carr e5, james d6, chapman-rounds m6, fumero e7, schuchardt m7, grada a8* (*corresponding author: ayman.grada@almirall.com) actinic keratosis (ak) is a pre-malignant skin lesion caused by long-term sun exposure. if untreated, ak may progress to squamous cell carcinoma, so early and effective treatment is essential. there is a lack of direct comparative studies for existing field therapies for ak, and our systematic review (sr) and network meta-analysis (nma) aimed to generate indirect comparative data for the available treatments. we conducted a sr and nma to compare the evidence from randomized controlled trials (rcts) on the efficacy, safety, and discontinuations of key field-directed treatments for ak (5-fu, imiquimod, ingenol mebutate, diclofenac sodium, pdt), plus a novel topical treatment, tirbanibulin. background and objectives email: yhec@york.ac.uk website: www.yhec.co.uk http://tinyurl.com/yhec-facebook http://twitter.com/yhec1 http://tinyurl.com/yhec-linkedin figure 2: results of the primary analysis searches identified 4,128 records. following assessment, 83 documents, reporting on 46 studies, were included. six of these studies were not suitable for inclusion in the nma due to insufficient or inappropriate reporting of data, or a lack of similarity with the other studies. feasibility assessment confirmed that the level of similarity between the studies to be included in the nma was acceptable. between-study heterogeneity was generally low (<40%), but for a comparison between tirbanibulin and topical placebo, it was moderate (56%). sensitivity analysis did not raise major concerns; random effects models and weakly informative prior distributions were used to allow for this heterogeneity. the third nma assumption is consistency between direct and indirect comparisons, and its assessment did not raise any major concerns. complete clearance was the only suitable outcome for nma, with the primary analysis conducted on studies assessing one course or session of treatment. in addition to topical placebo, six interventions were included in the network (see figure 1a). given the overlap between credible intervals shown in the statistical plots, treatment efficacy appeared similar for all active treatments. all treatments, including tirbanibulin, were better than placebo and diclofenac 3%. based on the zero rate of discontinuations due to traes and the low percentage of severe lsrs, tirbanibulin appears to have a particularly favourable safety profile. figure 1: network diagrams: complete clearance results conclusions contact us http://www.minerva-network.com/ methods eligible interventions were topical therapies, photodynamic therapy (pdt) following the use of sensitizer cream, and cryotherapy. eight databases, two trials registers, five websites and a selection of conference proceedings were searched between june and september 2020. following a feasibility assessment, a bayesian network meta-analysis (nma) was conducted, reporting odds ratios and credible intervals (i.e. confidence intervals in the bayesian framework) for complete clearance and safety outcomes. two sets of analyses were proposed; primary analyses would include only the results of studies offering participants one course or session of treatment (a trial design comparable with that of the two tirbanibulin rcts), while the secondary analyses would include results of studies offering any number of courses or sessions of treatment, plus retreatment where offered. figure 3: results of the secondary analysis although the review captured data on the incidence of severe local skin reactions (lsrs), the number of studies reporting each of the individual severe lsrs was relatively low, with a maximum of five studies reporting an individual severe lsr for the primary analysis. this data was not sufficient to support nma of the incidence of any severe lsrs. a qualitative assessment of discontinuations due to treatment-related adverse events (traes) showed that in the primary analysis rates were between 1.4% (pdt with 5aminolevulinic acid sensitizer) and 8.2% (imiquimod 5% for 16 weeks) in all active arms. tirbanibulin showed no discontinuations due to traes out of 353 patients across two rcts, and each of the severe lsrs were observed in <10% of patients, with no skin complications (hypo/hyper-pigmentation, scarring) observed. due to the zero counts it was not possible to conduct nma of the outcome, but the qualitative assessment indicates that the safety profile of the new treatment is favourable. a secondary analysis of studies (assessing any number of courses or sessions of treatment; see figure 1b) enabled the addition to the analysis of one placebo and five active treatments. the primary analysis showed that diclofenac 3% was the least efficacious of the active treatments (figure 2). based on the overlap of credible intervals shown in the statistical plots, the novel topical treatment (tirbanibulin 1% ointment) appeared to be as efficacious as existing treatments, and more so than topical placebo or diclofenac 3%. results of the secondary analysis (figure 3) confirmed these findings, with diclofenac and placebo pdt appearing substantially less efficacious than the remaining non-placebo treatments. 1 2 dr. george martin dermatology associates university of miami miller school of medicine, miami, florida and center for clinical and cosmetic research, aventura florida 3 professor of dermatology, pathology, and social sciences & health policy wake forest university health sciences, winston-salem, nc, usa 4 southern california clinical and translational science institute, and keck school of medicine at university of southern california, usa 5 york health economics consortium, york, uk 6 quantics biostatistics, edinburgh, uk 7 8 almirall, barcelona, spain almirall (us) results (continued) a. primary analysis b. secondary analysis mailto:ayman.grada@almirall.com mailto:yhec@york.ac.uk http://www.yhec.co.uk/ http://tinyurl.com/yhec-facebook http://twitter.com/yhec1 http://tinyurl.com/yhec-linkedin http://www.minerva-network.com/ field treatments for actinic keratosis: a systematic review and network meta-analysis skin december 2018 volume 2 supplemental issue copyright 2018 the national society for cutaneous medicine 105 rising derm stars silver sulfadiazine retards wound healing in mice via alterations in cytokine expression angelo landriscina, md, jamie rosen, md, allison kutner, md, brandon l. adler, md, aimee e. krausz, md, joshua d. nosanchuk, md, and adam j. friedman, md background: silver sulfadiazine (ssd), a broad-spectrum antimicrobial agent, has been the gold standard for burn wound treatment for decades. however, several studies have demonstrated its inferiority when compared to other wound healing adjuvants.1,2 this study aimed to elucidate ssd’s impact on wound healing and suggest mechanisms by which it occurs. methods: thermal burns were induced on the dorsal surface of balb/c mice; mice were split into two groups: untreated control (n=56) and ssd-treated (n=46) (50μl of 1% ssd cream per wound daily). daily photographs and image j software were used to asses change in wound area relative to day 0. histologic samples were stained using hematoxylin and eosin (h&e), masson’s trichrome, ionized calcium-binding adapter molecule-1(iba-1) and myeloperoxidase (mpo) to visualize morphology, collagen deposition, macrophages and neutrophils respectively. burn wounds were harvested for cytokine analysis (n= 10 wounds, 5 animals per group) and tissue samples were analyzed in duplicate for cytokine expression using mouse cytokine antibody array and cytokine signal intensity was measured using quantity one software. results: topical ssd applied to the wound bed significantly delayed wound closure compared to controls. by day 3 post-burn, both controls and ssd-treated wounds expanded compared to day 0, however the extent was significantly greater in the ssdtreated group (49.7 vs 23.8%, p<0.0002). by day 10, the ssd-treated group demonstrated 16.3% closure relative to day 0, as compared to 42.1% closure in controls (p<0.005) [figure 1]. wound histology and immunohistochemistry revealed more and persistent inflammatory granulation tissue and delayed collagen deposition in the wound bed as compared to controls over time, with increased neutrophil and decreased macrophage infiltration identified by myeloperoxidase and iba-1 staining respectively. cytokine analysis on day 3 revealed an absence of several proinflammatory factors including monocyte chemotactic protein(mcp)-1, macrophage inflammatory protein(mip)-1α and interleukin-1 receptor antagonist(il-1ra), which were present in untreated tissue. expression of interleukin(il)-1α and macrophage inflammatory protein(mip)-2 were significantly lower than controls. on day 7, significantly lower levels of il-1α, il-1ra, mip-1α and mip-2 were noted in the ssd group with complete absence of mcp-1 [figure 2]. discussion: our findings have several implications for the mechanisms by which skin december 2018 volume 2 supplemental issue copyright 2018 the national society for cutaneous medicine 106 ssd impedes wound healing. treatment with ssd alters the cytokine milieu resulting in aberrant recruitment and activation of macrophages. the inflammatory reaction in wound healing is regulated by a delicate balance between proand anti-inflammatory cytokines, with the il-1 family regulating chemokine production by keratinocytes, fibroblasts and macrophages.3,4 while expression of the il-1 family is dependent on the complex interplay between members of the family, given our results, we hypothesize that ssd alters gene expression of il-1 family genes resulting in impaired downstream cytokine production and ultimately delayed wound healing. while these data suggest a causal relationship by which ssd retards wound healing, further investigations are necessary to fully assess the degree of this effect. this study also underscores the importance of evaluating the immunologic effects of drugs in order to fully understand their mechanism of action. figure 1 figure 2 references: references: 1. v genuino ga, baluyut-angeles kv, espiritu ap, lapitan mc , buckley bs. topical petrolatum gel alone versus topical silver sulfadiazine with standard gauze dressings for the treatment of superficial partial thickness burns in adults: a randomized controlled trial. burns 2014;40:126773. 2. rashaan zm, krijnen p, klamer rr, schipper ib, dekkers om , breederveld rs. nonsilver treatment vs. silver sulfadiazine in treatment of partialthickness burn wounds in children: a systematic review and meta-analysis. wound repair regen 2014;22:473-82 3. ishida y, kondo t, kimura a, matsushima k , mukaida n. absence of il-1 receptor antagonist impaired wound healing along with aberrant nfkappab activation and a reciprocal suppression of tgf-beta signal pathway. j immunol 2006;176:5598606. 4. jurjus a, atiyeh bs, abdallah im, jurjus ra, hayek sn, jaoude ma et al. pharmacological modulation of wound healing in experimental burns. burns 2007;33:892-907. introduction • patients with moderate plaque psoriasis (i.e., 5% to 10% psoriasis-involved body surface area [bsa]1) often receive no treatment or are undertreated with topical monotherapy.2,3 • apremilast, an oral, small-molecule phosphodiesterase 4 inhibitor,4 was shown to be effective and demonstrated acceptable tolerability in patients with moderate to severe psoriasis (bsa ≥10%) in the effi cacy and safety trial evaluating the effects of apremilast in psoriasis (esteem) phase iii clinical trial program.5,6 • evaluating apremilast in a phase iv trial of effi cacy and safety in patients with moderate plaque psoriasis (unveil) (clinicaltrials.gov: nct02425826) is the fi rst prospective randomized, placebo (pbo)-controlled trial to demonstrate the clinical effi cacy and safety of a systemic treatment (apremilast) in systemicand biologic-naive patients with moderate plaque psoriasis. apremilast 30 mg twice daily (apr) was clinically effective and well tolerated during the 16-week, double-blind, pbo-controlled phase. • the effi cacy and safety results of the open-label apr treatment phase up to week 52 are presented. methods patients key inclusion criteria • males or females ≥18 years of age • chronic plaque psoriasis for ≥6 months before screening • moderate plaque psoriasis at screening and baseline as defi ned by bsa of 5% to 10% and static physician’s global assessment (spga) of 3 (moderate) based on a scale ranging from 0 (clear) to 5 (very severe) • no prior exposure to systemic or biologic treatments for psoriasis, psoriatic arthritis, or any other condition that could affect the assessment of psoriasis  key exclusion criteria • infl ammatory or dermatologic condition, including forms of psoriasis other than plaque psoriasis • topical therapy within 2 weeks or phototherapy within 4 weeks of randomization study design • unveil is a phase iv, multicenter, randomized, pbo-controlled, double-blind study (figure 1). • patients were randomized (2:1) to receive apr or pbo during weeks 0 to 16; patients in the pbo group were switched to apr at week 16. • all patients continued taking apr through week 52. figure 1. the unveil study design primary end point: mean percentage change in pgaxbsa at week 16 ra n d o m iz e 1: 2§screen* placebo (n=73) placebo-controlled phase apremilast 30 mg bid (n=148) open-label treatment phase safety observation apremilast 30 mg bid‡ (n=64) –5 weeks week 16 week 52 week 0 week 56 clinicaltrials.gov: nct02425826 *screening up to 35 days before randomization. §all doses were titrated over the fi rst week of treatment. ‡at week 16, all placebo patients were switched to open-label apremilast 30 mg bid (with dose titration) through week 52. bid=twice daily; pgaxbsa=product of the static physician’s global assessment and body surface area involvement. methods (cont’d) effi cacy assessments primary effi cacy • the primary effi cacy end point was the mean percentage change from baseline at week 16 in pgaxbsa, which represents the product of spga and bsa scores. • overall bsa affected by psoriasis is estimated based on the patient’s palm area, which equates to approximately 1% of total bsa. • for the 6-point spga, for plaques in all involved areas, the severity of erythema, scaling, and plaque elevation each were scored; scores were averaged and rounded to the nearest whole number.7 secondary effi cacy • proportions of patients achieving: – ≥75% reduction from baseline in pgaxbsa score (pgaxbsa-75) – spga response, defi ned as a score of 0 (clear) or 1 (almost clear) qol • quality of life (qol) was assessed with the dermatology life quality index (dlqi).8 safety assessments • safety was evaluated based on adverse events (aes), vital signs, clinical laboratory testing, and complete physical examinations. statistical analysis • effi cacy and qol assessments were conducted for the intent-to-treat (itt) population, which included all randomized patients; safety assessments were conducted in all randomized patients who received ≥1 dose of study medication. • mean percentage change from baseline in pgaxbsa and change from baseline in dlqi total score at week 16 were compared between apr and pbo using a 2-sided analysis of covariance model with treatment and site as factors and baseline value as covariate. • pgaxbsa-75 and spga responses at week 16 were evaluated with 2-sided cochran-mantel-haenszel tests stratifi ed by site. • effi cacy and qol parameters at week 52 were evaluated descriptively. – week 16 and week 52 apr/apr analyses were performed with the itt population. – week 52 pbo/apr analyses were performed with the modifi ed itt population (all patients who entered the apr extension phase). • the last-observation-carried-forward methodology was used to impute missing values. • safety assessments were summarized using frequencies and percentages. results patients • a total of 221 patients were randomized to study treatment and constitute the itt population; 185 patients (84%) completed the pbo-controlled phase (weeks 0 to 16) and 136/185 patients (74%) completed the apr treatment phase (weeks 16 to 52). • demographics and baseline disease characteristics were generally similar between treatment groups (table 1). – at baseline, mean dlqi total scores were comparable between treatment groups, and the mean pruritus visual analog scale score was slightly higher in the pbo group. table 1. patient demographics and baseline disease characteristics characteristic pbo n=73 apr n=148 age, mean (sd), years 51.1 (13.7) 48.6 (15.4) male, n (%) 41 (56.2) 74 (50.0) body mass index, mean (sd), kg/m2 30.8 (6.5) 30.5 (7.4) duration of psoriasis, mean (sd), years 13.9 (12.6) 17.5 (13.9) pgaxbsa score, mean (sd) 21.6 (5.9) 21.8 (5.3) bsa, mean (sd), % 7.1 (1.8) 7.2 (1.6) pasi score (0–72), mean (sd) 8.0 (3.2) 8.2 (4.0) dlqi total score, mean (sd) 11.1 (6.5) 11.0 (6.5) prior topical therapy, n (%) 59 (80.8) 122 (82.4) pasi=psoriasis area and severity index. results (cont’d) • at week 16, signifi cantly greater improvement in pgaxbsa occurred in patients receiving apr vs. pbo (figure 2). • at week 52, improvement was maintained in the apr/apr group and emerged in the pbo/apr group after switching to apr. figure 2. mean percentage change in pgaxbsa at week 16 and week 52 10 0 -10 -20 -30 -40 -50 -60 -70 m ea n pe rc en ta ge c ha ng e fr om ba se lin e in p ga xb sa s co re week 16 week 52 pbo n=73 apr n=147 pbo/apr n=64 apr/apr n=147 –10.2 –48.1 * –42.2 –49.0 *p<0.0001. error bars represent 95% confi dence intervals (cis). • signifi cantly more patients treated with apr achieved pgaxbsa-75 response at week 16 vs. pbo (figure 3). • pgaxbsa-75 response was maintained in the open-label apr treatment phase. figure 3. patients achieving pgaxbsa-75 response at week 16 and week 52 week 52 pbo/apr n=64 apr/apr n=147 12.3 * 35.4 45.3 37.4 60 50 40 30 20 10 0pe rc en ta ge o f p at ie nt s ac hi ev in g pg ax bs a75 r es po ns e week 16 pbo n=73 apr n=147 *p=0.0001. response defi ned as ≥75% reduction from baseline in pgaxbsa score. error bars represent 95% cis. • signifi cantly more patients treated with apr achieved an spga score of 0 or 1 at week 16 vs. pbo (figure 4). • long-term spga response was maintained with apr treatment in the open-label treatment phase. figure 4. patients achieving spga score of 0 (clear) or 1 (almost clear) at week 16 and week 52 week 52 pbo/apr n=64 apr/apr n=148 9.6 * 30.4 35.9 29.1 50 0 pe rc en ta ge o f p at ie nt s ac hi ev in g sp ga s co re o f 0 o r 1 week 16 40 30 20 10 pbo n=73 apr n=148 *p<0.0001. error bars represent 95% cis. results (cont’d) • improvement in dlqi was signifi cantly greater with apr than pbo at week 16 (figure 5). • dlqi improvement was maintained in patients continuing on apr for up to 52 weeks, and developed after patients were switched from pbo to apr. figure 5. mean change in dlqi at week 16 and week 52 0 m ea n ch an ge f ro m b as el in e in d lq i t ot al s co re week 16 week 52 -1 -2 -3 -4 -5 -6 -7 pbo n=71 apr n=144 pbo/apr n=63 apr/apr n=144 –2.4 –4.8 * –5.1 –4.3 -8 *p=0.0008. error bars represent 95% cis. • most aes were mild or moderate (table 2). • the most common aes (reported in ≥5% patients in either treatment group during the pbo-controlled period) included diarrhea, headache, nausea, upper respiratory tract infection, decreased appetite, and vomiting. table 2. overview of adverse events weeks 0 to 16 weeks 0 to 52 patients, n (%) pbo n=73 apr n=147 apr* n=211 n (%) eair/100 pt-yrs n (%) eair/100 pt-yrs n (%) eair/100 pt-yrs ≥1 ae 35 (47.9) 262.3 92 (62.6) 459.8 142 (67.3) 242.7 ≥1 serious ae 0 (0) 0.0 3 (2.0) 7.4 10 (4.7) 6.8 ≥1 severe ae 1 (1.4) 4.9 3 (2.0) 7.5 5 (2.4) 3.4 ae leading to drug withdrawal 3 (4.1) 14.5 5 (3.4) 12.4 14 (6.6) 9.6 most common aes§, n (%) diarrhea 12 (16.4) 63.7 43 (29.3) 139.8 59 (28.0) 53.8 nausea 7 (9.6) 35.4 26 (17.7) 73.7 40 (19.0) 31.8 headache 8 (11.0) 42.4 30 (20.4) 89.2 32 (15.2) 24.9 nasopharyngitis 2 (2.7) 9.8 5 (3.4) 12.5 22 (10.4) 16.2 upper respiratory tract infection 3 (4.1) 14.8 10 (6.8) 25.2 15 (7.1) 10.7 vomiting 2 (2.7) 9.7 9 (6.1) 22.9 12 (5.7) 8.4 decreased appetite 4 (5.5) 19.6 6 (4.1) 15.3 11 (5.2) 7.7 *includes all patients exposed to apr, including those initially randomized to pbo and switched at week 16 to apr. §reported by ≥5% of patients in any treatment group; listed in order of incidence over 52-week period. pt-yrs=patient-years. eair/100 pt-yrs=exposure-adjusted incidence rate per 100 patient-years, calculated as (number of events*100)/(total exposure time [in years] of safety population). the exposure time for a patient without a specifi c event is the treatment duration, whereas the exposure time for a patient with the specifi c event is the treatment duration up to the start date (inclusive) of the fi rst occurrence of the specifi c event. conclusions • apr was clinically effective in systemicand biologic-naive patients with moderate plaque psoriasis (bsa of 5% to 10%). • apr signifi cantly improved pgaxbsa score, pgaxbsa-75 response rate, spga 0 or 1 response rate, and dlqi total score at week 16 compared with pbo. • clinical responses were maintained with continued apr treatment through week 52 and emerged in patients who switched from pbo to apr at week 16. • the incidence of aes, based on eair per 100 patient-years, did not increase with longer exposure to apr. • safety and tolerability were consistent with previous studies5,6; no new safety or tolerability issues were observed up to 52 weeks. references 1. menter a, et al. j am acad dermatol. 2011;65:137-174. 2. armstrong aw, et al. jama dermatol. 2013;149:1180-1185. 3. lebwohl mg, et al. j am acad dermatol. 2014;70:871-881. 4. schafer ph, et al. cell signal. 2014;26:2016-2029. 5. papp k, et al. j am acad dermatol. 2015;73:37-49. 6. paul c, et al. br j dermatol. 2015;173:1387-1399. 7. walsh ja, et al. j am acad dermatol. 2013;69:931-937. 8. finlay ay, et al. clin exp dermatol. 1994;19:210-216. acknowledgments the authors acknowledge fi nancial support for this study from celgene corporation. the authors received editorial support in the preparation of this report from amy shaberman, phd, of peloton advantage, llc, parsippany, nj, usa, sponsored by celgene corporation, summit, nj, usa. the authors, however, directed and are fully responsible for all content and editorial decisions for this poster. correspondence bruce strober – brucestrober30@me.com disclosures bs: abbvie, amgen, astrazeneca, boehringer ingelheim, celgene corporation, dermira, eli lilly, forward pharma, janssen, leo pharma, maruho, medac, novartis, pfi zer, stiefel/glaxosmithkline, sun pharma, and ucb – honoraria as a consultant and advisory board member; abbvie, amgen, celgene corporation, eli lilly, janssen, merck, novartis, and pfi zer – payments (to the university of connecticut) as an investigator; corrona psoriasis registry – fees as a scientifi c director; abbvie and janssen – grant support (to the university of connecticut for fellowship program). jb: abbvie, amgen, boehringer ingelheim, celgene corporation, janssen, leo pharma, eli lilly, novartis, pfi zer, and valeant – advisory board member, speaker, consultant, and/or research support; sun pharma – consultant. ml: mount sinai, which receives funds from boehringer ingelheim, celgene corporation, eli lilly, janssen/johnson & johnson, kadmon, medimmune/ astrazeneca, novartis, pfi zer, and vidac. lsg: celgene corporation, leo pharma, novartis, pfi zer, and stiefel/ glaxosmithkline – investigator and/or consultant. jmj: abbvie, amgen, celgene corporation, dermira, galderma, genentech, janssen, lilly, medimetriks, merck, novartis, pfi zer, promius, and topmd – research, honoraria, consulting, and/or other support. jg & el: celgene corporation – employment. kcd: abbvie, amgen, boehringer ingelheim, bristol-myers squibb, celgene corporation, centocor/janssen, eli lilly, novartis, pfi zer, regeneron, stiefel, and xenoport – consultant, steering committee member, advisory board member, has received grants, and/or has received honoraria. presented at: the 2017 fall clinical dermatology conference; october 12–15, 2017; las vegas, nv. effi cacy and safety of apremilast in patients with moderate plaque psoriasis with lower bsa (unveil phase iv study) bruce strober, md1; jerry bagel, md2; mark lebwohl, md3; linda stein gold, md4; j. mark jackson, md5; joana goncalves, md6; eugenia levi, pharmd6; kristina callis duffi n, md7 1university of connecticut, farmington, ct, and probity medical research, waterloo, on, canada; 2treatment center of central new jersey, east windsor, nj; 3icahn school of medicine at mount sinai, new york, ny; 4henry ford health system, west bloomfi eld, mi; 5university of louisville, forefront dermatology, louisville, ky; 6celgene corporation, summit, nj; 7university of utah, salt lake city, ut fc17postercelgenestroberefficacyunveilstudy.pdf patient-reported outcomes in subjects with atopic dermatitis treated with tapinarof cream: results from a phase 2b, randomized parallel-group study amy s. paller, md;1 linda stein gold, md;2 anna m. tallman, pharmd;3 david rubenstein, md, phd4 1northwestern university feinberg school of medicine, chicago, il, usa; 2henry ford medical center, west bloomfield, mi, usa; 3dermavant sciences, inc., new york, ny, usa; 4dermavant sciences, inc., durham, nc, usa synopsis ■ atopic dermatitis (ad) is a chronic relapsing skin disease1 characterized by pruritus, burning sensations, xerosis, erythematous papules and plaques, exudation, crusting, and lichenification2 ■ patients with ad report an impact on sleep, quality of life, and psychosocial domains (social, academic, and occupational) due to persistent, intense pruritus, and the stigma associated with having visibly diseased skin1,2 ■ the primary goal in the treatment of ad is to stabilize the disease and reduce the number of flares1 ■ tapinarof cream is a therapeutic aryl hydrocarbon receptor modulating agent (tama) under investigation for the treatment of ad and psoriasis ■ this phase 2b dose-finding study (clinicaltrials.gov id: nct02564055) was designed to assess the efficacy and safety of tapinarof cream in adolescents and adults with ad ■ the primary analysis showed that tapinarof cream was efficacious and well tolerated in adolescents and adults with ad2 objectives ■ to present patient-reported outcomes from the phase 2b study in subjects with ad following treatment with topical tapinarof cream, including adolescent and adult impression of change in severity of ad symptoms and pruritus, changes in expanded patient-oriented eczema measure (poem), and daily sign and symptom severity diary scores methods study design ■ in this multicenter (united states, canada, and japan), phase 2b, double-blind, vehicle-controlled randomized study, subjects with ad were randomized 1:1:1:1:1:1 to receive tapinarof cream 0.5% or 1% once (qd) or twice daily (bid) or vehicle qd or bid for 12 weeks and followed up for 4 more weeks (figure 1) figure 1. study design tapinarof 1% bid (n= 40) tapinarof 1% qd (n= 41) tapinarof 0.5% bid (n= 43) tapinarof 0.5% qd (n= 41) vehicle bid (n= 42) vehicle qd (n= 40) offtreatment double-blind treatment (12 weeks) r adult and adolescent subjects with moderate to severe ad • aged 12–65 years • bsa ≥5%–≤35%* • iga ≥3 (n=247) follow up (4 weeks) *excluding scalp. ad, atopic dermatitis; bid, twice daily; bsa, body surface area; iga, investigator global assessment; qd, once daily. study outcomes and statistical analysis ■ the primary endpoint was the proportion of subjects with an investigator global assessment (iga) score of clear or almost clear (0 or 1) and ≥2-grade improvement in iga score from baseline to week 122 ■ subject-reported outcomes assessed in this study included subject impression of severity of ad symptoms, overall change in severity of ad symptoms, overall change in severity of pruritus symptoms, the expanded poem, and a daily sign and symptom severity diary – subjects were asked to rate the overall severity of their ad symptoms and overall severity of their pruritus symptoms at baseline on a scale ranging from 1 ‘mild’ to 4 ‘very severe’ – the change in overall severity of ad symptoms and pruritus symptoms from baseline to week 12 was rated by subjects from 1 ‘very improved’ to 7 ‘very worse’ – the expanded poem consisted of seven symptoms (skin that is itchy, bleeding, weeping or oozing, cracked, flaking, dry or rough, and disturbed sleep) measured using a 5-point scale of frequency of occurrence during the previous week plus three additional questions to assess sleep – the self-administered daily sign and symptom severity diary assessed the severity of 11 disease-related signs and symptoms (skin that is itchy, discolored, bleeding, oozing, cracked, scaly, flaky, dry or rough, painful, burning, and stinging). response options were on an 11-point numeric rating scale and ranged from 0 ‘absent’ to 10 ‘worst imaginable’ ■ incidence, frequency, and nature of adverse events (aes) and serious aes were collected from the start of study treatment until end of study visit at week 16 ■ no formal hypothesis tests were planned results subject characteristics ■ a total of 247 subjects (of 363 subjects originally screened) were randomized into the study at 32 sites in the united states, eight sites in canada, and 13 sites in japan (intent-to-treat analysis population) ■ of those randomized, 191 subjects (77%) completed the study including the week 16 follow-up visit ■ overall, mean demographic and baseline characteristics were comparable across treatment groups (table 1) ■ most subjects (91%) had a baseline iga score of 3 (moderate) and a baseline mean eczema area and severity index (easi) score of 11.3 (standard deviation 6.0) ■ primary endpoint: iga response rates (defined as iga score 0 or 1 and ≥2-grade improvement) at week 12 were higher in the tapinarof cream groups than the vehicle groups (53% [1% bid], 46% [1% qd], 37% [0.5% bid], 34% [0.5% qd] vs 24% [vehicle bid] and 28% [vehicle qd]) and were maintained for 4 weeks after the end of study treatment (non-responder imputation method)2 table 1. baseline subject demographics and characteristics tapinarof 1% cream tapinarof 0.5% cream vehicle bid (n=40) qd (n=41) bid (n=43) qd (n=41) bid (n=42) qd (n=40) mean age, years (sd) 28.5 (13.9) 31.6 (15.7) 29.0 (15.9) 29.3 (14.0) 27.9 (14.7) 29.4 (15.2) aged 12–17 years, n (%) 11 (28) 13 (32) 13 (30) 12 (29) 13 (31) 11 (28) aged 18–65 years, n (%) 29 (73) 28 (68) 30 (70) 29 (71) 29 (69) 29 (73) male sex, n (%) 22 (55) 17 (41) 26 (60) 19 (46) 19 (45) 23 (58) iga score, mean (sd) 3.1 (0.2) 3.1 (0.3) 3.1 (0.3) 3.1 (0.3) 3.1 (0.4) 3.1 (0.3) easi score, mean (sd) 9.8 (5.2) 10.9 (6.1) 13.1 (6.7) 11.4 (5.8) 11.1 (5.9) 11.1 (5.8) % bsa affected, mean (sd) 14.8 (8.7) 18.7 (11.0) 19.7 (10.5) 17.6 (9.9) 14.5 (9.2) 16.0 (10.3) pruritus score, mean (sd)* 5.2 (2.3) 5.4 (1.9) 5.7 (2.5) 5.7 (2.0) 5.1 (2.0) 5.8 (1.9) *mean scores based on a numeric rating scale of 0 ‘absent’ to 10 ‘worst imaginable’. data provided for the safety analysis population (n=247). bid, twice daily; bsa, body surface area; easi, eczema area and severity index; iga, investigator global assessment; qd, once daily; sd, standard deviation. subject impressions ■ at baseline, 86% of subjects rated their ad symptoms as moderate or severe across all treatment groups: 28–60% rated as moderate and 28–53% rated as severe ■ at week 12, a greater proportion of subjects in the tapinarof cream groups (81–89% in the 1% groups and 83–91% in the 0.5% groups) rated the overall severity of their ad symptoms as ‘very/moderately improved’ compared with 64–68% in the vehicle groups (figure 2a) ■ at week 12, a greater proportion of subjects in the tapinarof cream groups (78–87% in the 1% groups and 80–81% in the 0.5% groups) rated the overall severity of their pruritus symptoms as ‘very/moderately improved’ compared with 47–64% in the vehicle groups (figure 2b) expanded poem ■ at week 12, improvements were observed in all tapinarof cream and vehicle-treated groups on all seven poem items, except for the question relating to weeping or oozing for the 1% bid group ■ the three additional items in the expanded poem showed overall sleep quality improved across all treatment groups, with the largest improvements in the tapinarof cream groups – for item 8 related to how many nights subjects woke up at least once because of ad, the mean change reductions were largest in the tapinarof cream 0.5% groups (bid: –1.3 and qd: –1.2) – for items 9 and 10 related to how difficult it was it for subjects to fall asleep or fall back asleep after waking because of ad, the number of subjects finding it difficult or very difficult to fall (back) asleep were lower in all treatment groups at week 12 compared with baseline, except for one subject in the vehicle bid group for item 10 figure 2a. subject impression of change in severity of ad symptoms at week 12 81 89 91 83 64 68 6 3 9 14 18 20 0 0 03 11 12 p ro p o rt io n o f su b je ct s, % very/moderately improved 0 10 20 30 40 50 60 100 70 80 90 minimally improved no change tapinarof 1% bid (n=36) tapinarof 1% qd (n=37) tapinarof 0.5% bid (n=32) tapinarof 0.5% qd (n=35) vehicle bid (n=28) vehicle qd (n=25) results derived from the itt analysis population. hatched portion of bar corresponds to proportion of subjects with ‘moderately improved’ symptoms. ad, atopic dermatitis; bid, twice daily; itt, intent-to-treat; qd, once daily. figure 2b. subject impression of change in severity of pruritus symptoms at week 12 78 87 81 80 47 64 6 33 16 14 6 32 16 0 8 14 8p ro p o rt io n o f su b je ct s, % very/moderately improved 0 10 20 30 40 50 60 100 70 80 90 minimally improved no change tapinarof 1% bid (n=36) tapinarof 1% qd (n=37) tapinarof 0.5% bid (n=32) tapinarof 0.5% qd (n=35) vehicle bid (n=28) vehicle qd (n=25) results derived from the itt analysis population. hatched portion of bar corresponds to proportion of subjects with ‘moderately improved’ symptoms. bid, twice daily; itt, intent-to-treat; qd, once daily. daily sign and symptom severity diary ■ the highest mean baseline scores were seen for dry or rough, red or discolored, and flaky skin – overall, there was an improvement in dry or rough, red or discolored, and flaky skin in all treatment groups as measured by the daily sign and symptom severity diary scores, with the improvement being consistently smaller for the vehicle bid group vs the active tapinarof treatment groups for all items safety ■ overall, 51% (127/247) of subjects had treatment-emergent aes (teaes): 56% in the tapinarof cream groups and 41% in the vehicle groups, and were mostly mild to moderate in severity ■ the most frequently reported teae was nasopharyngitis (table 2) table 2. safety overview and most common teaes (occurring in ≥5% of subjects in any group) preferred term, n (%) tapinarof 1% cream tapinarof 0.5% cream vehicle bid (n=40) qd (n=41) bid (n=43) qd (n=41) bid (n=42) qd (n=40) any teae 28 (70) 22 (54) 20 (47) 23 (56) 19 (45) 15 (38) treatment-related teaes 6 (15) 6 (15) 8 (19) 4 (10) 6 (14) 2 (5) serious teaes 1 (3) 0 0 0 0 0 discontinuations due to teaes 1 (3) 0 5 (12) 1 (2) 4 (10) 2 (5) teae by intensity mild 14 (35) 14 (34) 11 (26) 14 (34) 12 (29) 7 (18) medium 14 (35) 8 (20) 6 (14) 8 (20) 4 (10) 8 (20) moderate 0 0 3 (7) 1 (2) 3 (7) 0 teaes occurring in ≥5% of subjects in any group nasopharyngitis 3 (8) 5 (12) 4 (9) 1 (2) 4 (10) 3 (8) folliculitis 4 (10) 8 (20) 3 (7) 3 (7) 0 0 dermatitis atopic 2 (5) 0 3 (7) 1 (2) 4 (10) 5 (13) urti 4 (10) 2 (5) 3 (7) 2 (5) 3 (7) 1 (3) headache 4 (10) 1 (2) 1 (2) 3 (7) 0 2 (5) acne 2 (5) 0 1 (2) 3 (7) 1 (2) 0 impetigo 1 (3) 0 0 0 0 3 (8) teae was defined as an ae that occurred on or after study treatment start date and on or before the last visit. ae, adverse event; bid, twice daily; qd, once daily; teae, treatment-emergent adverse event; urti, upper respiratory tract infection. conclusions ■ in all tapinarof cream groups, a greater proportion of subjects (81–91%) reported ad signs and symptoms as ‘very/moderately improved’ after 12 weeks compared with the vehicle groups (64–68%) ■ similarly, a greater proportion of subjects in the tapinarof cream groups (78–87%) reported the overall severity of pruritus as ‘very/moderately improved’ after 12 weeks compared with the vehicle groups (47–64%) ■ overall, tapinarof cream was well tolerated and these results correspond to the previously reported clinical efficacy findings2 ■ study findings demonstrated that tapinarof cream represents an important potential advance in topical medicine development, with beneficial effects on patient-reported outcomes in adolescents and adults with ad references 1. drucker am et al. j invest dermatol. 2017;137:26–30; 2. peppers j et al. j am acad dermatol. 2018; doi: 10.1016/j.jaad.2018.06.047 acknowledgments the authors thank the participating investigators, patients and their families, as well as colleagues involved in the conduct of the study. the authors acknowledge dr. james lee, former employee of dermavant sciences, inc. for his contribution to the abstract. editorial and medical writing support under the guidance of the authors was provided by apothecom, uk and was funded by dermavant sciences, inc. in accordance with good publication practice (gpp3) guidelines (ann intern med. 2015;163:461–464). contact dr. amy s. paller at apaller@nm.org with questions or comments. skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 14 original research effect of pre-surgical education on patient satisfaction and surgical experience: a quality improvement initiative brayden healey, do1, mckenna abercrombie, do1, hope barone, do1, morgan mcneil, do1, zijan zheng, do1, peter sigal, do1, ann lafond, md1 1department of dermatology, st. joseph mercy hospital ann arbor, ypsilanti, mi patient satisfaction is an ever-important aspect of providing patient-centered medical care. prior research has repeatedly demonstrated the effect of physiciandirected communication on patient satisfaction and therapeutic efficacy of treatment1,2. in the past two decades, patient satisfaction has become increasingly important in medical reimbursement models utilizing hospital consumer assessment of healthcare provider and systems (hcahps) scores3. hcacps is a scoring system that rates hospitals on aspects of clinical care including satisfaction with staff, facilities, and perception of care quality. hospital systems with higher hcahps scores are reimbursed at a higher rate abstract purpose: surgical procedures for malignant and benign cutaneous diseases are commonly performed in the outpatient dermatology clinic. for patients, these procedures can be accompanied by significant uncertainty, angst, and feelings of unpreparedness. in some instances, this uncertainty may contribute to adverse events such as the development of deep venous thrombosis or pulmonary emboli due to unnecessarily held anticoagulants. methods: we performed a prospective cohort study evaluating the impact of pre-surgical informative phone calls on patient satisfaction with their surgical experience. surgical patients scheduled at our academic dermatology clinic for excision or mohs surgery were randomly assigned to a “call”/intervention group or “non-call”/control group. patients in the intervention group were called by their resident surgeon one evening prior to their procedure. the resident discussed a pre-written script of expectations and preparations for the surgical day and post-operative period, and allotted time for patients to ask questions. patients from both groups were given identical five-point likert scale surveys to complete on the day of their suture removal, which varied from 7-14 days after the procedure. data analysis was performed using spss. means and one-tail t-test for each question were calculated to compare the call group to the non-call group. results: patients in the call group reported higher rates of overall satisfaction, satisfaction with answers to questions, overall preparation, and overall rating of surgical experience while also reporting lower levels of fear and anxiety. of these findings, differences in level of preparedness were statistically significant. conclusions: the results suggest that presurgical phone calls to patients may improve patient education, help address their concerns and questions, improve their satisfaction with care, and can potentially limit adverse events. introduction skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 15 through the hospital value-based purchase program. importantly, higher hcahps scores have also been associated with higher quality care and lower re-admission rates3. intentional efforts towards patient communication and treatment regimen clarification can lead to a higher efficacy of treatment and a lower rate of adverse events2. in our academic dermatology clinic, patients are often scheduled for surgical treatment of malignant or benign cutaneous lesions via phone after having previously been seen in person for their initial evaluation. this scheduling pattern occurs because treatment is often dictated by biopsy results, which are not available until after the patient's in-person visit. as such, there may not be an opportune time for a physician-patient discussion of the procedure and expectations until the day of the procedure itself. the purpose of this quality improvement initiative was to evaluate the effect of conducting presurgical informative phone calls focused on patient preparedness, anxiety, fear, and overall satisfaction. in addition, although not directly measured, secondary objectives included increasing patient understanding of their surgical procedure and medical necessity and limiting adverse events by clarifying presurgical antibiotic and anticoagulant use. a prospective cohort study was developed in which patients scheduled for surgical intervention at our academic dermatology office were randomized into intervention and control groups. surgical procedures that met inclusion criteria included mohs micrographic surgery and standard surgical excision of benign and malignant lesions. patients undergoing cosmetic procedures including neurotoxin injections, injectable dermal fillers, microneedling procedures, chemical peels, and laser therapies were excluded. patients in the intervention group were called via phone by their assigned resident surgeon one evening prior to their procedure. during this phone call, the resident was instructed to read a predetermined script (addendum 1) discussing details of the surgical procedure and postoperative period. patients were allotted time to ask questions and clarify information provided by the physician. in the event that a patient in the intervention group was unable to be reached by phone, they would, by default, become part of the control group. subsequently, when patients presented for suture removal and postoperative evaluation, they were given a voluntary postoperative survey (addendum 2) including six short questions written in basic english with five-point likert scale answer choices. these questions evaluated the patients’ preoperative questions, overall preparedness, fear, apprehension, or anxiety and overall surgical experience. means and standard deviations were calculated for each question by group and the p-values of the t-tests were determined. during the study period from 10/26/2020 to 1/22/2021, 87 patients were enrolled with 61 in the intervention group and 26 in the control group. the overall level of satisfaction for both groups was similar, with a mean 4.48 (sd = 1.05) for the control group and 4.51 (sd = 1.13) for the intervention group (p = 0.915). the intervention group had a slightly higher rating of how well their questions were answered with a mean of 4.85 (sd = 0.57) compared to 4.58 (sd = 0.64) for the control group (p = 0.051). the intervention group also felt more prepared for their procedure methods results skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 16 than those in the control group (m = 4.87 vs. 4.62 respectively). this difference was statistically significant (p = 0.0249). the level of fear/anxiety was slightly lower for the intervention group, with mean of 2.25 (sd = 1.22), compared to 2.5 (sd = 1.21) for the controls (p = 0.375). patients in the intervention group rated their surgical experience more highly with a mean overall rating of 4.66 (sd = 0.54) as opposed to 4.46 (sd = 0.71) for the controls (p = 0.168). table 1 shows the means and standard deviations by group as well as the p-value of the t-test for responses to each question. table 1. intervention vs. control group responses mean (sd) pvalue not called (n=26) called (n=61) overall satisfaction 4.48 (1.05) 4.51 (1.13) 0.915 questions answered 4.58 (0.64) 4.85 (0.57) 0.051 how prepared 4.62 (0.64) 4.87 (0.39) 0.0249 level of fear/anxiety 2.5 (1.21) 2.25 (1.22) 0.375 rate experience during surgery 4.46 (0.71) 4.66 (0.54) 0.168 this quality improvement initiative reveals that patients who received a presurgical phone call had a significantly higher rate of overall preparedness for their surgical procedure. additionally, patients reported higher rates of overall satisfaction, satisfactorily answered questions, overall experience rating, and lower levels of fear and anxiety, though these were not statistically significant. the lack of statistical significance in these categories may be attributed to a limited sample size. these findings, however, suggest a trend toward improvement in many areas of the patient experience surrounding dermatologic surgical procedures. while not directly quantified in this initiative, some resident physicians involved in making phone calls reported incidents of clarifying the need to continue anticoagulation without interruption. in these instances, without the presurgical phone call, patients may have inappropriately discontinued their anticoagulants and increased the risk of severe adverse events including potential for dvts and pes. there were several limitations to this study. there was a large discrepancy in group sizes; many patient demographics were missing, including history of prior skin procedures, which could cause bias in those who have had multiple mohs or skin cancer excisions; patients may have been influenced to respond more positively or negatively as a result of their initial encounters receiving the diagnosis and discussing treatment rather than only as a result of the intervention; finally, patients were not randomized into intervention and control groups. future studies would be beneficial to elucidate a mechanism of reducing adverse events with a similar physician-led approach to presurgical patient education. additionally, these trends toward increased patient satisfaction may be further examined on a larger scale with various aspects of clinical care to optimize hcahps scores and subsequent reimbursement while simultaneously improving outcomes2. pre-surgical phone calls made by resident physicians can increase patient satisfaction with their dermatologic surgical experience. this practice may also limit adverse events, improve outcomes, and secondarily optimize reimbursement in the era of patientsatisfaction-based reimbursement. discussion conclusion skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 17 conflict of interest disclosures: none funding: none corresponding author: mckenna abercrombie, do 5333 mcauley dr. suite 5003 ypsilanti, mi 48197 (719) 237-4444 email: mckennaabercrombiedo@gmail.com references: 1. prakash b. patient satisfaction. j cutan aesthet surg. 2010;3(3):151-155. 2. lewis e, samperi s boyd-skinner c. telephone follow-up calls for older patients after hospital discharge. age ageing. 2017; 46 (4): 544-546. 3. chen hc, cates t, taylor m cates c. improving the us hospital reimbursement: how patient satisfaction in hcahps reflects lower readmission.int j health care qual assur. 2020; ahead-of-print (ahead-of-print): 333-344. 4. díez-álvarez e, arrospide a, mar j, alvarez u, belaustegi a, lizaur b, et al. effectiveness of pre-operative education in reducing anxiety in surgical patients. enferm clin. 2012; 22 (1): 18-26. 5. amjad ali, sarfraz masih, fazle rabbi abdur rasheed. effect of nurse led education on anxiety level among coronary artery bypass grafting pre-operative patients. j pak med assoc. 2020;: 1-13. 6. iyengar s, yeager dg, cohen jl, ozog dm. . update and review of bleeding considerations in dermatologic surgery. dermatologic surgery. 2020;46(2):192–201. skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 18 supplemental material addendum 1 pre-surgery preparation provider script 1. you can eat and take all your medications including your blood thinners prior to your surgery. 2. you will not need any pain medications prior to the surgeryand you should not need any prescription pain medications after the surgery. 3. plan to wear loose fitted clothing for easy access of the surgical site. 4. you should be able to drive yourself to and from the surgical appointment. you may bring a support person, but during covid they will need to wait in the car. 5. appointment length: a) excisions: your appointment will be approximately 1 hour long. b) mohs: your appointment will be approximately 2 hours long. this will vary depending on what we see under the microscope when we remove your skin cancer. 6. your surgery will take place in the office under local anesthesia, you will not be “asleep”, but alert and oriented during the entirety of the surgery. you will not feel pain. 7. the surgical site may be inflamed and bruise for a few days after your surgery, which is normal. plan to reduce your physical activity for 1-2 weeks after your surgery. 8. there will be stitches placed which will need to be removed at a follow up appointment in one to two weeks. 9. you will have a scar that should heal, but redness of the area may remain for months. skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 19 addendum 2 post-operative survey 1. overall, how satisfied are you with your recent surgical experience? 1 very dissatisfied 2 somewhat dissatisfied 3 neither 4 somewhat satisfied 5 very satisfied 2. were your questions adequately addressed prior to your surgery? 1 not at all 2 somewhat 3 neutral 4 mostly addressed 5 thoroughly addressed 3. how prepared did you feel for your procedure and after procedure care? 1 very unprepared 2 somewhat unprepared 3 neither 4 somewhat prepared 5 very prepared 4. how would you rate your level of fear, apprehension or anxiety prior to your surgery? 1 none 2 barely any 3 mild 4 moderate 5 severe 5. how would you rate your experience during your surgery? 1 terrible 2 not good 3 neutral 4 good 5 excellent 6. did you receive a phone call from your resident surgeon the day prior to your surgery? yes no a. if so, how satisfied were you with the information received during this phone call? 1 very dissatisfied 2 somewhat dissatisfied 3 neither 4 somewhat satisfied 5 very satisfied background • acne vulgaris (av) is a chronic inflammatory disease that affects approximately 85% of adolescents and can also present in preand post-adolescents1 • oral antibiotics of the tetracycline class, including doxycycline and minocycline, are first-line therapies for moderate-to-severe acne; however, there are concerns with systemic side effects (eg, hyperpigmentation, phototoxicity, autoimmune disorders)2,3 • fmx101, minocycline foam 4%, is a novel, stable foam formulation of minocycline that has been previously demonstrated in a phase 2 study to be an effective and well-tolerated treatment for moderate-to-severe acne4 • two identical phase 3, randomized, double-blind studies were conducted to evaluate the efficacy and safety of the topical administration of fmx101 4% in the treatment of moderate-to-severe av – the 2 studies consisted of a 12-week double-blind phase followed by a 9-month open-label phase • this report presents data from the completed double-blind phase methods • two phase 3 (study 04 and study 05), randomized, double-blind, vehicle-controlled trials evaluated the safety and efficacy of fmx101 4% in the treatment of moderate-to-severe av (figure 1) – patients were randomized 2:1 to receive either fmx101 4% or a foam vehicle – foam was self-applied once daily for 12 weeks figure 1. study design • • • • • • • *subjects with ≥1-grade iga improvement. iga=investigator’s global assessment. results • 961 subjects (study 04: n=466; study 05: n=495) were enrolled in the studies • baseline demographics and disease characteristics are shown in table 1 table 1. baseline demographics and disease characteristics   study 04 study 05 fmx101 4% (n=307) vehicle (n=159) fmx101 4% (n=333) vehicle (n=162) demographics mean age (range), years 20.5 (11-52) 20.0 (10-57) 20.5 (10-55) 20.8 (11-54) male/female, % 45.3 / 54.7 38.4 / 61.6 40.8 / 59.2 42.6 / 57.4 ethnicity (white, black, other), % 62.5, 28.0, 9.5 62.9, 25.2, 11.9 73.0, 21.9, 5.1 76.5, 18.5, 5.0 inflammatory lesions, n mean (range) 32.2 (20-50) 31.6 (20-76) 31.6 (20-69) 32.3 (20-50) noninflammatory lesions, n  mean (range) 49.5 (25-100) 46.5 (25-98) 50.0 (25-100) 50.9 (26-104) iga score, n (%)  3 – moderate 255 (83.1) 137 (86.2) 296 (88.9) 148 (91.4) 4 – severe 52 (16.9) 22 (13.8) 37 (11.1) 14 (8.6) efficacy • after 12 weeks of treatment, subjects treated with fmx101 4% had a significantly greater reduction in inflammatory lesion count from baseline vs vehicle in both studies (figure 2a, b) • fmx101 4% was superior to vehicle for the first co-primary end point in the pooled analyses (all 961 subjects) (figure 2c) figure 2. co-primary end point – absolute change in inflammatory lesion count from baseline at week 12 • a greater proportion of subjects in both studies achieved iga treatment success with fmx101 4% vs vehicle at week 12 (figure 3a, b) – however, a statistically significant difference was achieved only in study 05; a numerical superiority was achieved in study 04 • in the pooled analysis of the 2 studies, fmx101 4% was significantly superior to vehicle for the second co-primary end point of iga treatment success (figure 3c) figure 3. co-primary end point – iga treatment success at week 12 • the percentage reduction in inflammatory lesions was significantly greater for fmx101 4% vs vehicle in both studies (figure 4) – a significantly greater reduction was observed as early as week 3 with fmx101 4% figure 4. percentage change from baseline to week 12 in inflammatory lesions by visit fmx101 (n=307) vehicle (n=159) fmx101 (n=333) vehicle (n=162) • subjects treated with fmx101 4% had a significantly greater reduction in noninflammatory lesion count from baseline at week 12 vs vehicle in both studies (figure 5a,b), as well as in the pooled analysis (figure 5c) figure 5. absolute change in noninflammatory lesion count from baseline at week 12 • there were high rates of subject satisfaction with using fmx101 4% (figure 6) – overall, 90% of subjects were satisfied with fmx101 4% – the majority of subjects were satisfied with fmx101 4% in comparison with previous acne products (ie, gels and creams), with its ease of use, and with the feel of the product on their skin figure 6. patient satisfaction questionnaire results (pooled analysis, n=534) safety • fmx101 4% was generally safe and well tolerated in both study 04 and study 05 • across the 2 studies, the percentage of subjects reporting treatment-emergent adverse events (teaes) ranged between 16.9% and 33% for fmx101 4%, vs 18.2% to 26.5% for vehicle (table 2) – 1 subject receiving fmx101 4% discontinued treatment in study 05 (ectopic pregnancy; not related to treatment), as compared with 4 subjects for vehicle across the 2 studies – 7 subjects reported 9 serious teaes across the 2 studies; all were considered not related to treatment – few treatment-related teaes were reported in both studies • the most common teaes in ≥2% of subjects were nasopharyngitis and headache (table 3) – dermal teaes were reported in <1% of all subjects in the fmx101 4% treatment groups; their severity was mostly mild • the majority (>95%)a of fmx101 4% subjects reported none or mild signs and symptoms for tolerability assessment parameters at week 12 (table 4) ªbased on observed cases. table 2. summary of treatment-emergent aes (teaes) study 04 study 05 fmx101 4% (n=307) vehicle (n=159) fmx101 4% (n=333) vehicle (n=162) subjects with any teae, n (%) number of teaes 52 (16.9) 78 29 (18.2) 35 110 (33.0) 169 43 (26.5) 80 subjects with any serious teae, n (%) number of serious teaes 1 (0.3) 1a 0 0 4 (1.2) 5b 2 (1.2) 3c subjects with any teae leading to study discontinuation, n (%) number of teaes leading to study discontinuation 0 0 3 (1.9) 4d 1 (0.3) 1e 1 (0.6) 1f subjects with any treatment-related teae, n (%) number of treatment-related teaes 6 (2.0) 7 4 (2.5) 6 9 (2.7) 10 3 (1.9) 4 asuicide attempt. bintestinal obstruction, intestinal perforation, facial bones fracture, ectopic pregnancy; asthma. cbiliary dyskinesia, cholecystitis, pneumonia. dapplication-site acne, application-site burn, application-site erythema, application-site pruritus. eectopic pregnancy. fhepatic enzyme increased. table 3. nondermal and dermal aes profile adverse event study 04 study 05 fmx101 4% (n=307) vehicle (n=159) fmx101 4% (n=333) vehicle (n=162) nondermal aes in ≥1% of subjects, % one or more 16.9 18.2 33.0 26.5 nasopharyngitis 2.0 3.8 7.2 3.7 headache 2.3 3.1 6.0 5.6 upper respiratory tract infection – – 1.8 1.2 ck increased 1.0 0.6 1.5 2.5 ligament sprain 0.3 1.3 1.8 0.6 nausea – – 1.2 0.6 vomiting – – 1.2 0.6 administration-site dermal aes, % acne worsening – 0.6 0.3 – burn – 1.3 – – dermatitis – – 0.3 – discolorationa 0.7 1.3 0.9 – discomfort 0.3 – – – erythema – 0.6 – – pruritus – 0.6 – – rash – – 0.3 0.6 aseveral terms were coded to “discoloration” including discoloration, yellow discoloration and, in 1 case, hyperpigmentation. ck=creatinine phosphokinase. table 4. tolerability assessment results at week 12 (based on observed cases) tolerability assessment, n (%) 0=none 1=mild 2=moderate 0=none 1=mild 2=moderate study 04 fmx 101 4% (n=267) vehicle (n=128) erythema 248 (92.9) 19 (7.1) – 124 (96.9) 4 (3.1) – dryness 250 (93.6) 17 (6.4) – 120 (93.8) 8 (6.3) – hyperpigmentationa 233 (87.3) 28 (10.5) 6 (2.2) 110 (85.9) 14 (10.9) 4 (3.1) skin peeling 259 (97.0) 8 (3.0) – 125 (97.7) 3 (2.3) – itching 254 (95.1) 12 (4.5) 1 (0.4) 124 (96.9) 3 (2.3) 1 (0.8) study 05 fmx101 4% (n=294) vehicle (n=136) erythema 238 (81.0) 49 (16.7) 7 (2.4) 102 (75.0) 29 (21.3) 5 (3.7) dryness 281 (95.6) 11 (3.7) 2 (0.7) 124 (91.2) 11 (8.1) 1 (0.7) hyperpigmentationa 237 (80.6) 44 (15.0) 13 (4.4) 118 (86.8) 15 (11.0) 3 (2.2) skin peeling 281 (95.6) 12 (4.1) 1 (0.3) 131 (96.3) 5 (3.7) – itchingb 274 (93.2) 18 (6.1) 2 (0.7) 123 (90.4) 12 (8.8) – ahyperpigmentation was most commonly used to describe localized post-inflammatory darkening of the affected skin. ba case of severe itching in the vehicle group. conclusions • the results of the 2 phase 3 studies showed that fmx101 4% was effective for the treatment of moderate-to-severe acne – there was significantly greater reduction of both inflammatory and noninflammatory lesions at week 12 from baseline with fmx101 4% vs vehicle in both study 04 and study 05, as well as in the pooled analysis (a co-primary end point) � a significant reduction in inflammatory lesions was observed as early as week 3 for fmx101 4% – the rate of iga treatment success was significantly greater for fmx101 4% vs vehicle in study 05, but not study 04 (a co-primary end point) � pooled analysis of iga treatment success was statistically significant for fmx101 4% • >95% of subjects had none or mild signs and symptoms at the week 12 assessment of dermal tolerability • fmx101 4% appeared to be safe and well tolerated, with dermal aes occurring in <1% of fmx101 4% subjects and no serious drug-related aes reported • there was high satisfaction with fmx101 4% • the fmx101 4% open-label phase is currently ongoing to determine long-term safety the efficacy and safety of fmx101, minocycline foam 4%, for the treatment of acne vulgaris: a pooled analysis of 2 phase 3 studies linda stein gold, md1; sunil dhawan, md2; jonathan weiss, md3; zoe diana draelos, md4; herman ellman, md5 1henry ford health system, detroit, michigan, usa; 2center for dermatology clinical research, inc., fremont, california, usa; 3gwinnett dermatology, braselton, georgia, usa; 4dermatology consulting services, high point, north carolina, usa; 5foamix pharmaceuticals, inc, bridgewater, new jersey, usa. references 1. picardo m, et al. dermatol ther (heidelb) 2017;7:43-52. 2. zaenglein al, et al. j am acad dermatol. 2016;74:945-973.e33. 3. smith k, leyden jj. clin ther 2005;27:1329-1342. 4. shemer a, et al. j am acad dermatol 2016;74:1251-1252. disclosures: this study was funded by foamix pharmaceuticals. dr. stein gold is speaker, consultant, or investigator for celgene, glaxosmithkline, janssen, kadmon, leo pharma, novartis, pfizer, regeneron pharmaceuticals, sun pharma, and valeant. dr. dhawan is an investigator or speaker for allergan, galderma, valeant, dr reddy’s, glenmark, abbvie, glaxosmithkline, foamix, dermira, aclaris, leo pharma, celgene, cutanea, regeneron, revance, amgen, ucb, novartis, pfizer, and merz. dr. weiss received grants for research from allergan, foamix, promius, galderma, and valeant, and he received honoraria for consulting from promius, galderma, valeant, and novan. dr. draelos received research grants from galderma, allergan, cutanea, valeant, and novan. dr. ellman is an employee of foamix pharmaceuticals. acknowledgment: editorial support was provided by princy john, pharmd, of p-value communications. fc17posterfoamixsteingoldefficacyfmx101acne.pdf skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 335 research letter analysis of self-reported data accuracy among board-certified and trainee dermatologists in the cms national provider identifier registry rebecca l. yanovsky, bs1, gideon p. smith, md mph phd2 1tufts university school of medicine, boston, ma 2department of dermatology, harvard medical school, massachusetts general hospital, boston, ma administrative burden is an increasing problem in medicine and was recently cited as the number one reason for burnout among academic dermatologists.1 one such administrative requirement is updating the national plan and provider enumeration system (nppes) database. this database includes a national provider identifier (npi) number, assigned to every healthcare provider as a permanent identifier through changes in location or training. the database also includes self-reported evolving meta-data on specialty, location, training level, and other details.2 the nppes database is currently being referenced for utilization studies in dermatology and has been proposed for mapping healthcare resources across the united states as well as including physicians in national surveys.3 in order to be effective, the data must be accurate. while studies exist on the accuracy of selfreported data in other specialties,4 the accuracy of the npi registry among dermatologists is unknown. data for all 181 dermatology residents and faculty from massachusetts general, brigham and women’s, and beth israel hospitals were extracted from the cms npi registry on 11/12/18 and cross-checked with known institutional data. these data were then compared with a recent study of radiologists,4 hypothesizing that dermatologists may have higher inaccuracy rates due to administrative burden. we also examined differences between residents and attendings. our null hypothesis was that accuracy would not be significantly different between the groups. fisher exact test was used to assess the hypotheses. high levels of inaccuracy were found across almost all categories, with residents having significantly higher rates of inaccuracy compared to attending physicians in reported specialty and state. 24% (43/181) of individuals had an incorrect primary taxonomy (specialty) listed. 10% (15/149) of attending dermatologists had an incorrect practice state listed. since initial registration, 56% (19/32) of residents, compared to only 5% (7/149) of attending physicians, had never updated their information. 4% (6/149) of attending physicians were still listed as students in a training program (table 1). when compared with radiologists, rates of inaccuracy did not significantly differ other methods introduction results skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 336 than for self-reported practice location where dermatologists’ inaccuracy was higher (p< .0001) (table 2). table 1. accuracy of self-reported certification and location in the cms national plan and provider enumeration system of board-certified and trainee dermatologists on a single day in november 2018, broken down by training status. residents (%) attendings (%) total (%) p n 32 149 181 never updated 19 (56.25) 7 (4.70) 25 (13.81) < .0001 incorrect primary taxonomy (specialty) 17 (53.13) 15 (10.07) 43 (23.76) < .0001 listed as student in training program 15 (46.88) 6 (4.03) 21 (11.60) < .0001 incorrect state 9 (28.13) 16 (10.74) 25 (13.81) .0095 incorrect address 18 (56.25) 85 (57.05) 103 (56.91) .934 incorrectly listed sole proprietor 4 (12.50) 23 (15.44) 27 (14.92) .674 no license number 9 (28.13) 4 (2.68) 13 (7.18) < .0001 average days since last updated 674.1 2072.4 1825.2 < .0001 table 2. accuracy of self-reported specialty and location in the cms national plan and provider enumeration system among dermatologists on a single day in november 2018, compared to similar study of radiologists3. dermatology residents (%) radiology residents3 (%) p dermatology attendings (%) radiology attendings3 (%) p n 32 39 149 124 incorrect primary taxonomy (specialty) 17 (53.13) 28 (71.79) .139 15 (10.07) 6 (4.84) .116 listed as student in training program 15 (46.88) 18 (46.15) 1.00 6 (4.03) 2 (1.61) .299 incorrect practice location 18 (56.25) 20 (51.28) .812 85 (57.05) 20 (16.12) < .0001 skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 337 upon applying for an npi number, providers agree to notify the npi enumerator within 30 days of any change.5 despite this agreement, the level of inaccuracy is high. this may be due to increased administrative burden or simply a result of a lack of awareness among dermatologists of the requirement to update this database. these inaccuracies have implications for dermatologists anywhere npi numbers are used, including validation of healthcare transactions, adverse actions from licensing authorities, and identification of providers in patient’s electronic medical records. inaccuracies also limit the intended applications of the npi system to increase healthcare efficiency and minimize fraud and abuse. while our study is limited by its crosssectional nature and to data from our own institutions due to knowledge of provider records for cross-referencing, we found similar patterns of non-compliance analyzing small samples of several dermatology programs across the country for whom we had independent provider details. inaccuracies may be a reflection of the particularly large administrative requirements in today’s medical environment that are progressively difficult to sustain. increased program support for younger trainees who have more frequent changes to their location, specialty, and license level may help mitigate outdated information and promote a higher degree of overall fidelity. for example, dermatology programs may be able to implement small administrative changes upon entry or graduation of trainees. simply increasing awareness among dermatologists of the requirement to update this national registry, which can be done online by logging in at https://nppes.cms.hhs.gov, may also increase accuracy and contribute to effective analysis, insights and future policies affecting our field. conflict of interest disclosures: none funding: none corresponding author: rebecca l yanovsky, bs tufts university school of medicine 145 harrison avenue boston, ma 02111 650-269-5622 rebecca.yanovsky@tufts.edu references: 1. dorrell dn, feldman sr, huang ww. the most common causes of burnout among u.s. academic dermatologists based on a survey study. journal of the american academy of dermatology. 2019. 2. hipaa administrative simplification: standard unique health identifier for health care providers. final rule. federal register. 2004;69(15):34333468. 3. hamid rn, mcgregor sp, siegel dm, feldman sr. assessment of provider utilization through skin biopsy rates. dermatologic surgery : official publication for american society for dermatologic surgery [et al]. 2019. 4. glover mt, prabhakar am, rao sk, weilburg jb, hirsch ja. accuracy of self-reported specialty and practice location among radiologists. journal of the american college of radiology : jacr. 2017;14(9):1169-1172. 5. national provider identifier (npi) application/update form. omb no. 09380931:https://www.cms.gov/medicare/cmsforms/cms-forms/downloads/cms10114.pdf. accessed 12/1/18. discussion https://nppes.cms.hhs.gov/ mailto:rebecca.yanovsky@tufts.edu microsoft word skin sept oa 1297 09092021 v2.docx skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 487 2021 ucb® resident research competition – 1st place original research association between rosacea, environmental factors, and facial cutaneous dysbiosis: a pilot study from the largest national festival of twins justin w. marson, md1, stefano berto, phd2, paul mouser, phd3, hilary e. baldwin, md4,5 1 suny downstate health sciences university, brooklyn, ny 2 medical university of south carolina, charleston, sc 3 acne cure alliance, morristown, nj 4 acne treatment & research center, brooklyn, ny 5 department of dermatology, rutgers robert wood johnson medical school, piscataway, nj rosacea is a chronic inflammatory disorder of the central face, characterized by transient or persistent erythema and telangiectasias, papules and/or pustules, phymotic changes and/or rare ocular manifestations.1 it is estimated that upwards of 10% of individuals are afflicted by rosacea, with over 16 million affected in the united states alone.2 current abstract background: to investigate the microbiome composition in individuals with and without rosacea and correlate findings to individual factors that may affect facial cutaneous and enteric microbiome composition. methods: participants with and without rosacea (as determined by a board-certified dermatologist) were surveyed regarding factors that may affect the facial cutaneous/enteric microbiome. microbiome samples were collected, analyzed for 16s sequences, and mapped to an optimized version of existing databases. r was used to perform mann-whitney/kruskal-wallis test for categorical comparisons. correlation between two continuous variables was determined with linear regression models. primary component analysis (pcoa) plots employed monte carlo permutation test to estimate p-values. all p-values are adjusted for multiple comparisons with the false discovery rate (fdr algorithm) using benjamini-hochberg. results: 84 individuals with rosacea and 44 controls were evaluated. individuals with rosacea were more likely to currently own pets (p = 0.029) and consume more alcohol (p = 0.006). absolute bacteria abundance were similar in facial cutaneous (p = 0.36) and enteral microbiome (p = 0.29). facial cutaneous microbiome showed significantly decreased richness and evenness (otu: p = 0.019; shannon: p = 0.049) and a three to four-fold decrease in abundance of 8 distinct cutaneous bacterial genera in rosacea. enteral microbiome analysis showed significant reduction in abundance of ruminococcaceae (fdr = 0.002) and blautia (fdr < 0.001) and increase in prevotellaceae (fdr = 0.024) in rosacea. conclusion: environmental factors may alter relative abundances of specific microbial genera and lead to microbiome diversity. further studies with increased sample sizes and higher severity cases may further elucidate the role of dysbiosis in rosacea. introduction skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 488 pathophysiology incorporates both environmental and genetic components that stimulate an overactive innate immune system and inflammatory reactions to the skin microbiome.1-3 more recent studies also suggest that this inflammation may have a systemic component given rosacea’s association with various inflammatory conditions, including crohn’s disease, ulcerative colitis, small intestinal bacterial overgrowth (sibo), and helicobacter pylori.4-8 the microbiome is a vast and varied collection of bacteria, viruses, and fungi whose composition has increasingly been demonstrated to have significant influence on whole-body health as well as development and maintenance of immunological activity.1,9 early exposure to commensal skin microbes and environmental factors affect the developing microbiome’s richness (i.e., diversity of organisms) and evenness (i.e., relative quantity of organisms present) and may influence the function of the immune system and inflammatory response.9-11 studies have found a correlation between the relative abundances of several cutaneous microbes, including notably demodex folliculorum (and its native microbe bacillus oleronius), virulent strains of staphylococcus epidermidis, cytotoxin-associated gene a positive (caga+) helicobacter pylori and chlamydophila pneumoniae, and rosacea.1,12-15 because of the multifactorial nature of the pathophysiology of rosacea, twin studies offer ways to control for genetic causes and isolate environmental factors. 3,16,17 while only 50% of genes are identical between fraternal twins, identical twins share all of their genes. as a result, they offer a unique opportunity to study not only heritability of diseases but also isolate and analyze the impact of environmental factors. the purpose of this study was to analyze the cutaneous and enteral microbiome and its role in rosacea and correlate findings to demographic/environmental information. this study was conducted in accordance with the declaration of helsinki, good clinical practices and local regulatory requirements. the studies were reviewed and approved by institutional review boards. all subjects provided their written informed consent prior to entering the studies. participants were recruited from attendees of the annual twinsburg festival in twinsburg, ohio during august 5-6 2017. participants ≥18 years-old were evaluated for rosacea by a board-certified dermatologist prior to completing a survey (with the aid of trained staff members as needed). information on demographics and factors that could affect the microbiome were obtained. facial swabs and fecal samples were collected for microbiome genomic data (additional information in supplement) and compared to existing databases to identify bacterial taxa abundance and differences within (alphadiversity) and between (beta-diversity) groups. analysis was performed using r. categorical comparisons were performed using the non-parametric mann-whitney test for two-category comparisons or the kruskal-wallis test for ≥3 categories. correlation between two continuous variables was determined with linear regression models, where p-values indicate the probability that the slope of the methods skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 489 regression line is zero. principle component analysis (pcoa) plots employed the monte carlo permutation test to estimate p-values. all p-values were adjusted for multiple comparisons with the false discovery rate (fdr algorithm) using benjamini-hochberg. 136 participants (rosacea, n = 88; control, n = 48) were included in the final analysis. participants were with rosacea were predominately female (70.5%), mean age 50.3 years (standard deviation ± 12) with mild to moderate rosacea (97.4%). notably, control counterparts were proportionally more likely to be female (97.9%) (table 1). fitzpatrick score between participants with and without rosacea was significantly different (p<.001) with a skew towards lower phototype in individuals with rosacea. participants with rosacea reported consuming more alcoholic beverages/week than controls (2.42 vs 0.78, p=.006) and were more likely to currently own pets (72.4% vs 52.1%, p = .029) (table 2). regular use of over the counter skin care products did not significantly differ between groups. there was no significant difference between absolute microbial counts between rosacea and control in either facial (30,880 vs 29,533, p=.36) or enteric (14,198 vs 13,566, p = .29) microbiomes (figure 1 a&b). intra-sample (alpha-diversity) richness and evenness was significantly less in the facial cutaneous microbiome of participants with rosacea versus control (operational taxonomic units (otu): p = 0.019; shannon: p = 0.049)(figure 2a&b). no significant difference was found when comparing the enteric microbiome between groups (otu: p = 0.96; shannon: p = 0.49)(figure 2 c&d). between groups (betadiversity) there was a significant difference within respective facial cutaneous microbiome (p= .024, r2 = 0.037, f-statistic = 3.21) but not in the enteric microbiome (p = .256, r2 = .0152, f-statistic = 1.27) (figure 2 e&f). table 1. participant demographics. there was a significant difference in phototype distribution between participants with and without rosacea. participants with rosacea reported consuming more alcoholic beverages per week than their control counterparts. rosacea (n = 88) control (n = 48) p-value iga – n (%) mild 43 (55.1) moderate 33 (42.3) severe 2 (2.6) age – mean (sd) 50.3 (12) 46.75 (13.4) 0.116 female gender – n (%) 62 (70.5%) 47 (97.9%) < 0.001 fitzpatrick score – n (%) <0.001 2 54 (61.4) 26 (54.2) 3 31 (35.2) 8 (16.7) 4 3 (3.4) 8 (16.7) 5 0 (0.0) 6 (12.5) drinks/week – mean (sd) 2.42 (4.0) 0.78 (1.1) 0.006 table 2. potential microbiome-altering factors. participants with rosacea were significantly more likely to report currently owning a pet than their control counterparts rosacea (n = 88) control (n = 48) pvalue pet ownership – n (%) pets in childhood 79 (89.8) 45 (93.8) 0.642 pets now 63 (72.4) 25 (52.1) 0.029 caesarean section – n (%) 17 (19.3) 8 (17.4) 0.969 breast fed – n (%) 20 (23.3) 7 (28.0) 0.824 skin care – n (%) moisturizer 51 (58.0) 30 (62.5) 0.739 facial cleanser 62 (70.5) 35 (72.9) 0.916 sunscreen 64 (72.7) 33 (68.8) 0.770 results skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 490 figure 1. absolute bacterial abundance. scatterplot with superimposed box-plot demonstrating distribution of absolute abundance of all bacteria within facial cutaneous (a) and enteric microbiome (b). no significant difference was found between the bacterial load within the microbiome between participants with and without rosacea. wilcoxon signed-rank test used for non-parametric comparison with p<.05 demonstrating significance. there was a 3-4 fold decrease in abundance of facial cutaneous bacterial genera streptococcus (fdr = 0.015; fdr = 0.004), corynebacterium (fdr = 0.003), actinomyces (fdr = 0.015), lactococcus (fdr = 0.016), veillonella (fdr < 0.001) and chloroplast (fdr = 0.015) in rosacea compared to control (figure 3a). in the enteric microbiome, there was significant reduction in abundance of ruminococcaceae (8-fold reduction; fdr = 0.002) and blautia (2-fold reduction; fdr < 0.001) and a 6-fold increase in prevotellaceae (fdr = 0.024) in rosacea compared to control (figure 3b). data suggests that, although primarily thought of as an inflammatory condition of the central face, rosacea’s classically cutaneous dysregulated inflammatory response may extend systemically, especially given associations with multiple gastrointestinal, metabolic, and neurological disorders.5-8,15,18 studies have previously implicated species such as demodex folliculorum (and its native microbe bacillus oleronius), virulent strains of staphylococcus epidermidis, cytotoxin-associated gene a positive (caga+) helicobacter pylori, chlamydophila pneumoniae and lesser known organisms of the facial (gordonia, geobacilus) and enteric (peptococcaceae, methanobrevibacter, acidaminococcus and megasphaera) microbiome in the dysbiosis that may play a role in rosacea’s (systemic) inflammatory response.1,5,12-17 our findings demonstrated a correlation between rosacea and decreased diversity (richness) and relative of abundance (evenness) of organisms within the facial cutaneous microbiome of individual’s with rosacea. interestingly, significantly more participants with rosacea reported currently owning pets and consuming more alcohol which may play a role in instigating or propagating the observed dysbiosis. discussion skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 491 figure 2. diversity in the facial cutaneous and enteric microbiome. alpha diversity (differences within a sample) showed significantly less diversity/richness in bacteria (operational taxonomic units (otus))(a) and evenness (shannon)(b) in facial cutaneous but not in enteric microbiome (c&d). beta-diversity (differences between samples across groups) assessed with principal component analysis with weighted unifrac (accounting for number of different species and relative abundance) demonstrated clustering of the microbiome samples that were significantly different for facial cutaneous microbiome (e) but not for the enteric microbiome (f). p-value calculated with mann-whitney u with false discovery rate corrections using benjamini-hochberg. skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 492 figure 3. differential abundances of bacterial genera. volcano plot demonstrating -log2 fold changes in abundance of bacterial genera within the facial cutaneous (streptococcus (s53inte7, fdr = 0.015; s53gor30, fdr = 0.004), corynebacterium (unc00dmg, fdr = 0.003), actinomyces (unc0045t, fdr = 0.015), lactococcus (gfqlac54, fdr = 0.016), veillonella (unc04ol2, fdr < 0.001) and chloroplast (jzzpseu2, fdr = 0.015)) (a) and enteric (ruminococcaceae (unc01220, fdr = 0.002) and blautia (unc02f9r, fdr < 0.001) and prevotellaceae (unc05o3s, fdr = 0.024))(b) microbiome. to the authors knowledge, the implicated species within the facial cutaneous (and enteric microbiome) have not yet been widely investigated in rosacea pathogenesis. this may suggest that dysbiosis as a whole, as opposed specific virulent or beneficial species, may play a (more central) role in the inflammation seen in rosacea. the current study did not find alterations within the diversity of the enteric microbiome, which may be due to a limited sampling of participants with (more) severe rosacea who may have a more dysregulated systemic inflammatory response. there are some reports in the literature that suggest improving epidermal barrier dysfunction in rosacea may improve disease severity.19,20 interestingly, our sample reported no significant difference in over the counter skin care usage. this may be due to limited sample size or reporting/recall bias and should be further explored in future studies. limitations include relatively small sample size comprised of mostly mild-moderate rosacea that may limit statistical power, detection of deviations in microbiome diversity and composition, and ability to perform intra-twin variability. participants were recruited from a regional festival which may limit result generalizability to other populations. retrospective survey results may also be subject to recall bias. rosacea is an inflammatory condition primarily of the central face that has been associated with systemic inflammatory conditions. dysbiosis of the facial cutaneous microbiome may be affected by an individual’s local environment and contribute to ongoing rosacea pathogenesis. future studies should investigate the causality between dysbiosis and rosacea pathophysiology and may benefit from more conclusion skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 493 highly powered twin studies to control for confounding genetic (and environmental) factors. conflict of interest disclosures: jwm, sb, pm have no relevant disclosures. heb is a speaker for galderma, valeant, sun, mayne, and bayer, and investigator for galderma and valeant. funding: study was funded in part by an unrestricted educational grant from galderma. technical support for microbiome analysis was provided by diversigen, inc. corresponding author: justin w. marson, md 450 clarkson ave brooklyn, ny 11203 email: justin.w.marson@gmail.com references: 1. marson jw, baldwin he. rosacea: a wholistic review and update from pathogenesis to diagnosis and therapy. int j dermatol. 2020 jun;59(6):e175-e182. doi: 10.1111/ijd.14757. epub 2019 dec 27. pmid: 31880327. 2. elewski, b. e., z. draelos, b. dreno, t. jansen, a. layton and m. picardo (2011). "rosacea global diversity and optimized outcome: proposed international consensus from the rosacea international expert group." j eur acad dermatol venereol 25(2): 188-200. 3. aldrich, n., m. gerstenblith, p. fu, m. s. tuttle, p. varma, e. gotow, k. d. cooper, m. mann and d. l. popkin (2015). "genetic vs environmental factors that correlate with rosacea: a cohort-based survey of twins." jama dermatol 151(11): 1213-1219. 4. searle t, ali fr, carolides s, al-niaimi f. rosacea and the gastrointestinal system. australas j dermatol. 2020 nov;61(4):307-311. doi: 10.1111/ajd.13401. epub 2020 aug 6. pmid: 32761824. 5. parodi, a., s. paolino, a. greco, f. drago, c. mansi, a. rebora, a. parodi and v. savarino (2008). "small intestinal bacterial overgrowth in rosacea: clinical effectiveness of its eradication." clin gastroenterol hepatol 6(7): 759-764. 6. marks, r., r. j. beard, m. l. clark, m. kwok and w. b. robertson (1967). "gastrointestinal observations in rosacea." lancet 1(7493): 739-743. 7. weiss, e. and r. katta (2017). "diet and rosacea: the role of dietary change in the management of rosacea." dermatol pract concept 7(4): 31-37. 8. egeberg, a., l. b. weinstock, e. p. thyssen, g. h. gislason and j. p. thyssen (2017). "rosacea and gastrointestinal disorders: a population-based cohort study." br j dermatol 176(1): 100-106. 9. uhr gt, dohnalová l, thaiss ca. the dimension of time in host-microbiome interactions. msystems. 2019 feb 19;4(1):e00216-18. doi: 10.1128/msystems.00216-18. pmid: 30801030; pmcid: pmc6381226. 10. scharschmidt, t. c., k. s. vasquez, h. a. truong, s. v. gearty, m. l. pauli, a. nosbaum, i. k. gratz, m. otto, j. j. moon, j. liese, a. k. abbas, m. a. fischbach and m. d. rosenblum (2015). "a wave of regulatory t cells into neonatal skin mediates tolerance to commensal microbes." immunity 43(5): 1011-1021. 11. hagerty sl, hutchison ke, lowry ca, bryan ad. an empirically derived method for measuring human gut microbiome alpha diversity: demonstrated utility in predicting health-related outcomes among a human clinical sample. plos one. 2020 mar 2;15(3):e0229204. doi: 10.1371/journal.pone.0229204. pmid: 32119675; pmcid: pmc7051054. 12. holmes, a. d. (2013). "potential role of microorganisms in the pathogenesis of rosacea." j am acad dermatol 69(6): 1025-1032. 13. picardo, m. and m. ottaviani (2014). "skin microbiome and skin disease: the example of rosacea." j clin gastroenterol 48 suppl 1: s85-86. 14. daou, h., paradiso, m., hennessy, k., seminariovidal, l., 2021. rosacea and the microbiome: a systematic review. dermatology and therapy 11, 1– 12.. doi:10.1007/s13555-020-00460-1 15. nam, j. h., y. yun, h. s. kim, h. n. kim, h. j. jung, y. chang, s. ryu, h. shin, h. l. kim and w. s. kim (2018). "rosacea and its association with enteral microbiota in korean females." exp dermatol 27(1): 37-42. 16. bataille v, lens m, spector td. the use of the twin model to investigate the genetics and epigenetics of skin diseases with genomic, transcriptomic and methylation data. j eur acad dermatol venereol. 2012;26(9):1067-1073. 17. zaidi, a. k., k. spaunhurst, d. sprockett, y. thomason, m. w. mann, p. fu, c. ammons, m. gerstenblith, m. s. tuttle and d. l. popkin (2017). "characterization of the facial microbiome in twins discordant for rosacea." exp dermatol. 18. wollina u. is rosacea a systemic disease? clin dermatol. 2019 nov-dec;37(6):629-635. doi: 10.1016/j.clindermatol.2019.07.032. epub 2019 jul 31. pmid: 31864441. 19. pelle mt, crawford gh, james wd. rosacea: ii. therapy. j am acad dermatol. 2004 oct;51(4):499512; quiz 513-4. doi: 10.1016/j.jaad.2004.03.033. pmid: 15389184. 20. subramanyan k. role of mild cleansing in the management of patient skin. dermatol ther. 2004;17 suppl 1:26-34. doi: 10.1111/j.13960296.2004.04s1003.x. pmid: 14728696. fc 2018 ferris poster -09132018 real-world experience and clinical utility of a non-invasive gene expression rule-out test for melanoma and additional validation against high risk driver mutations in braf, nras and the tert promoter laura ferris, md, phd1, burkhard jansen, md2, zuxu yao, phd2 , jim rock, ms2, maral skelsey, md3, gary peck, md4, and clay j. cockerell, md5 1department of dermatology, university of pittsburgh, pittsburgh, pa, 2dermtech, inc, la jolla, ca, 3department of dermatology, georgetown university school of medicine, washington, dc, 4dermatologic surgery center of dc, chevy chase, md, 5cockerell dermatopathology, dallas, tx methods synopsis 1. gerami p et al. development and validation of a non-invasive 2-gene molecular assay for cutaneous melanoma. j am acad dermatol, 2017;76(1)114-120.e2 2. ferris l et al. utility of a non-invasive 2-gene molecular assay for cutaneous melanoma and effect on decision to biopsy. jama dermatol, 2017; 153(7):675680 3. ferris l et al. real-world performance and utility of a non-invasive gene expression assay to evaluate melanoma risk in pigmented lesions. mel res, 2018; doi:10.1097/cmr.0000000000000478 4. hornberger j and siegel d. economic analysis of a non-invasive molecular pathologic assay for pigmented skin lesions. jama dermatol, 2018; 154(9)1-8 5. jansen b et al. gene expression analysis differentiates melanomas from spitz nevi. jdd, 2018; 17(5)574-576. • to assess the real-world utility of the pla and determine, if physicians follow the guidance of the test • to determine if braf, rnas and tert promoter mutations can be used as additional validation of pla gene expression and if combining gene expression and mutation analyses further improves test performance about 3 million surgical biopsies are performed in the us annually to diagnose fewer than 200,000 new cases of in situ and invasive melanomas using the current care standard of visual assessment and histopathology. tools that reduce the number of surgical biopsies performed on benign skin lesions have the potential to improve patient care and reduce cost. the non-invasive pigmented lesion assay (pla) is such a tool. it helps rule out melanoma and the need for surgical biopsies of pigmented skin lesions clinically suspicious of melanoma with a negative predictive value of over 99% by assessing linc and prame gene expression.1-5 analyses of over 20,000 pla samples in real-world routine-use settings in over 600 us dermatology offices demonstrate that only 12% of assessed lesions are pla(+) (gene expression consistent with melanoma; linc and/or prame detected). an ongoing real-world utility study of now over 500 cases demonstrates that clinicians follow the guidance of the pla by surgically biopsying all (100%) of pla(+) cases (n=61) while monitoring the vast majority (99%) of pla(-) cases thereby reducing surgical biopsies by almost 90% while missing fewer melanomas. to date, 461 pla(-) cases have been followed for 6 months and 272 cases have been followed for 1 year since the initial pla(-) test result was obtained. efforts to validate the pla beyond correlating it with histopathology demonstrated that somatic hotspot mutations in three genes known to be drivers of early melanoma development (braf other than v600e, nras and the tert promoter) could be detected in noninvasively collected pla samples in 2 patient cohorts with skin lesions clinically suspicious of melanoma. in cohort 1 samples (n=103, archival, histopathology available), at least one hotspot driver mutation was present in 77% of melanoma samples compared to only 14% in non-melanoma samples (p=0.0001). tert promoter mutations were the most prevalent mutation type in pla(+) melanomas. eighty-two percent of pla(-) lesions had no mutations and 97% of histopathologically confirmed melanomas were pla and/or mutation (+). mutation frequencies were similar (p=ns) in cohort 2 samples (n=519, prospectively collected real-world pla samples, histopathology not available) in which 88% of pla(-) samples had no detectable hotspot mutations. combining pla gene expression analyses for linc and prame and mutation analyses for braf other than v600e, rnas and the tert promoter enhances the ability to non-invasively detect early melanoma. all studies were irb approved. gene expression analyses were performed as previously described. mutation analyses were performed by sanger sequencing of adhesive patch and ffpe tissue block samples. objectives conclusions references conflict of interest disclosures: lf, ms, gp and cc are advisors and/or investigators, bj, zy and jr are employees of dermtech • the pla reduces surgical biopsies by 88% while missing fewer melanomas • a pla npv >99% correlates with a less than 1% probability of a negative test missing a melanoma compared to an npv of 83% for histopathology (17% probability of missing melanoma). • physicians follow the guidance of the test and surgically biopsy pla(+) lesions while pla(-) lesions are monitored. • hotspot driver mutation analyses further validate gene expression results – combining gene expression and mutation analyses further improves test performance. results we demonstrate in an ongoing real-world utility study of now over 500 representative cases that clinicians follow the guidance of the pla by surgically biopsying all (100%) of pla(+) cases (n=61) while monitoring the vast majority (99%) of pla(-) cases thereby reducing surgical biopsies by almost 90% while missing fewer melanomas. to date, 461 pla(-) cases have been followed for 6 months and 272 cases have been followed for 1 year since the initial pla(-) test result was obtained. ninety three percent that tested double positive for gene expression of both linc and prame were histopathologically classified as invasive melanoma or melanoma in situ. prame only and linc only lesions were assessed as melanomas histopathologically in 50% and 7%, respectively. assuming pla(-) results without a follow up biopsy are true negatives, a sensitivity of 95% and a specificity of 91% with a negative predictive value of >99% was calculated. an additional also ongoing survey of 594 pla routine-use cases in which clinicians self report actions taken further corroborates the pla’s utility 99.4% of pla(-) tests were not biopsied and monitored, 98.2% of pla(+) cases were biopsied (only a single linc only case without mutations was monitored). recent optimizations enabled the reliable extraction of both dna and rna from adhesive patch skin samples which made it possible to noninvasively analyze pigmented lesion cases suspicious for melanoma not only for gene expression via pla, but also for the presence of somatic mutations. mutation analyses in cohort 1 samples (n=103, archival, histopathology available) showed hotspot driver mutations (braf other than v600e, nras or tert promoter mutations) in 77% of the 30 melanoma cases but only in 14% of the 73 non-melanoma cases. the frequency of the assessed early hotspot driver mutations in histopathologically confirmed melanomas is statistically higher than the frequency in non-melanoma cases p<0.0001). ninety-seven percent of cases with a histopathologic consensus diagnosis of melanoma were either pla gene expression or mutation positive, and 48% of nonmelanomas were negative for expression of linc, prame and driver mutations, highlighting the allure of an approach that looks at both rna and dna risk factors in a single non-invasively obtained sample. tert promoter mutations were the most prevalent mutation type in pla positive melanomas (79%). braf v600e mutations were present at similar frequencies in melanoma and non-melanoma samples (in 10% and 8% respectively). conversely, braf v600k mutations (6%) and nras g61r and k5e (10%) mutations were found in melanomas only. thirty-eight percent of invasive and 17% of in situ melanomas harbored multiple hotspot mutations. figure 1 summarizes correlations of mutation, pla and histopathologic analyses. figure 1: correlation of mutation analyses (at least one braf non-v600e, nras or tert promoter hotspot mutation detected), pla gene expression analyses (linc and/or prame detected) and histopathologic analyses (consensus diagnosis) in cohort 1 samples (n=103). differences between melanoma and non-melanoma groups were highly statistically significant (p<0.0001). mel.pla.neg.: pla negative samples of histopathologically confirmed melanomas, mel.pla.pos.: pla positive samples of histopathologically confirmed melanomas, non.mel.pla.neg.: pla negative samples of histopathologically confirmed non-melanomas, non.mel.pla.pos.: pla positive samples of histopathologically confirmed non-melanomas. . to further corroborate the described hotspot mutation results in epidermal skin samples of pigmented skin lesions suspicious for melanoma, we compared findings from adhesive patch samples to findings in formalinfixed paraffin embedded (ffpe) tissue blocks of surgical biopsies from the same lesions. ninety-three percent of mutations detected in adhesive patch samples correlate with mutations in ffpe tissue blocks of the same lesions (n=41). subsequently, 519 prospectively collected real-world pla samples from cohort 2, 387 pla(-) and 132 pla (+) cases were analyzed for these same mutations and a similar difference in the frequency of hotspot driver mutations was found. eighty eight percent of real-world pla(-) samples were also negative for any of these melanoma related mutations, similar to the 82% in cohort 1. ten percent of pla negative cases harbored mutations in the tert promoter region. nras mutations (q61k and g60l) were found in 1% of pla (-) cases while none of these cases harbored g12 or g13 mutations. all braf mutations in pla (-) cases were v600e mutations (4%). pla(+) cases in real-world cohort 2 samples had mutation frequencies similar to the cohort 1 validation set. the two groups were not statistically different. figure 2 depicts the comparison of cohort 1 and 2 for the absence of mutations in pla (-) samples irrespective of histopathology (available only for cohort 1). figure 2: comparison of hotspot driver mutations in pla(-) cases of cohort 1 and cohort 2. pla(-) cases were assessed for the absence of braf (nonv600e), nras and tert promoter hotspot mutations. there were no statistically significant differences between cohort 1 and cohort 2 (p=ns). 82% 18% 0% 88% 12% 0% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 0 mut 1 mut 2 or more mut ab se nc e of m ut at io ns cohort 1 cohort 2 introduction objectives methods results patients, demographics, and clinical characteristics ● 1596 adult patients were randomized to tralokinumab 300 mg q2w (1196) or placebo (400) in the initial treatment period ● baseline demographics and clinical characteristics were well balanced between treatment groups (table 1) mean duration of atopic dermatitis was 28.2 years and around one-half of patients (49.7%) had iga 4 (severe disease) at baseline maintenance of week 16 responses at week 52 ● 412 patients achieved iga 0/1 and/or easi-75 at week 16 with tralokinumab q2w and were re-randomized (2:2:1) to continue tralokinumab q2w, tralokinumab q4w, or placebo in the maintenance treatment period ● a large proportion of the patients who continued tralokinumab q2w or q4w maintained iga 0/1 and/or easi-75 response at week 52 (42.4 to 57.3%), without using any rescue medication (including tcs) during the 36-week maintenance period for patients with iga 0/1 response at week 16, this response was maintained by 55.9%, 42.4%, and 34.0% of patients re-randomized to tralokinumab q2w, q4w, and placebo, respectively (figure 2a) easi-75 response was maintained by 57.3%, 50.4%, and 26.4%, respectively (figure 2b) iga 0/1 or easi-75 response was maintained by 56.2%, 50.0%, and 27.4% respectively, in patients who had previously achieved either or both responses (figure 2c) time to relapse ● in patients who achieved iga 0/1 with tralokinumab at week 16 without rescue medication use, median time to relapse was not reached for patients re-randomized to tralokinumab q2w or q4w relapse was defined as transfer to open-label treatment, first rescue medication, or discontinuation of investigational medicinal product due to lack of efficacy, ae, or for other reasons, where lack of efficacy could not be excluded the log-rank test p-values that resulted from the comparison of each of the tralokinumab treatment groups with placebo were p=0.004 for the tralokinumab q2w group and p=0.14 for the q4w group (figure 3a) ● in patients who achieved easi-75 with tralokinumab at week 16 without rescue medication use, median time to relapse was not reached for patients re-randomized to tralokinumab q2w or q4w the log-rank test p-values that resulted from the comparison of each of the tralokinumab treatment groups with placebo were p=0.002 for the tralokinumab q2w group and p=0.044 for the q4w group (figure 3b) time to response (open-label arm) ● at week 16, 686 patients who did not achieve iga 0/1 or easi-75 with tralokinumab were transferred to open-label treatment with tralokinumab 300 mg q2w with optional tcs ● the probability of achieving iga-0/1 and easi-75 increased throughout the open-label treatment period (figure 4) cumulative response rate based on time to first iga 0/1 in 685 patients was 38.6% by week 52 cumulative response rate based on time to first easi-75 response in 661 patients was 63.7%, by week 52 the probability of achieving clinical response criteria was greater earlier in the open-label period safety ● safety was assessed in all patients who received at least one dose of maintenance treatment ● the proportion of patients with one or more ae or serious ae was similar between the initial 16-week treatment period and the maintenance period (table 2) ● the majority of aes were mild or moderate in severity ● withdrawal from the trial due to an ae only occurred only in a small number of patients acknowledgments the ecztra 1 and 2 studies were sponsored by leo pharma assessing long-term maintenance of efficacy with tralokinumab monotherapy in patients with moderate-to-severe atopic dermatitis: combined results from two phase 3, randomized, double-blind, placebo-controlled trials (ecztra 1 and 2) andrew blauvelt,1 andreas wollenberg,2 andrew pink,3 ketty peris,4 april armstrong,5 lynda spelman,6 hidehisa saeki,7 charles lynde,8 pedro herranz,9 sebastien barbarot,10 eric simpson11 1oregon medical research center, portland, or, usa; 2department of dermatology and allergology, ludwig-maximilian university of munich, munich, germany; 3st. john’s institute of dermatology, guy’s and st. thomas’ hospitals, london, uk; 4dermatology, catholic university and fondazione policlinico universitario a. gemelli, irccs, rome, italy; 5department of dermatology, keck school of medicine at the university of southern california, los angeles, ca, usa; 6veracity clinical research, brisbane, queensland, australia, and probity medical research, woolloongabba, queensland, australia; 7department of dermatology, nippon medical school, tokyo, japan; 8lynde dermatology, probity medical research, markham, ontario, canada, and department of medicine, university of toronto, ontario, canada; 9department of dermatology, hospital universitario la paz, madrid, spain; 10centre hospitalier universitaire de nantes, nantes, france; 11department of dermatology, oregon health & science university, portland, or, usa ● atopic dermatitis is a chronic, type 2 inflammatory skin disease, characterized by excessive skin dryness, red or inflamed skin, and intense itching1-3 ● tralokinumab is a fully human, immunoglobulin g4 monoclonal antibody that specifically binds to and neutralizes interleukin (il)-13, preventing receptor interaction and subsequent downstream signaling, thus inhibiting the pro-inflammatory activity of il-13 in atopic dermatitis4-8 ● early improvements in disease severity and symptoms in adults with moderate-to-severe atopic dermatitis were observed in two pivotal phase 3 clinical trials with tralokinumab monotherapy (ecztra 1 and 2)9 significantly more patients receiving tralokinumab monotherapy achieved investigator’s global assessment (iga) 0/1 and eczema area and severity index reduction of 75% (easi-75) compared with placebo at week 16 ● there is a need for additional insight into dosing over time for atopic dermatitis treatments in addition, reducing the dosing frequency of a long-term medication while maintaining efficacy may have positive implications for patient adherence and health care costs ● to investigate the long-term efficacy beyond 16 weeks of tralokinumab monotherapy in adult patients with moderate-to-severe atopic dermatitis pooled from two phase 3 trials, including: the maintained efficacy in patients achieving an iga score of 0 or 1 and/or easi-75 at week 16 and continuing with tralokinumab once every two weeks (q2w), once every 4 weeks (q4w), or placebo ● to monitor the clinical response in patients who did not achieve an iga score of 0 or 1 (clear or almost clear skin) or easi-75 at week 16, who continued on open-label tralokinumab treatment plus optional topical corticosteroids (tcs) study design and patients ● ecztra 1 (nct03131648) and ecztra 2 (nct03160885) were identically designed, multinational, double-blind, randomized, placebo-controlled, 52-week trials of tralokinumab monotherapy ● patient eligibility criteria and stratification factors can be found in figure 1 ● at week 16, tralokinumab responders (patients who achieved iga 0/1 and/or easi-75 with tralokinumab) were re-randomized 2:2:1 to maintenance treatment with tralokinumab 300 mg q2w or q4w, or placebo (in the primary analysis, patients who used rescue medication, including tcs, were considered to be non-responders) ● patients who did not achieve iga 0/1 and/or easi-75 at week 16 were transferred to open-label treatment with tralokinumab 300 mg q2w, with optional use of tcs up to week 52 analyses ● maintenance of response (iga 0/1, easi-75, or both) was assessed at week 52 in a prespecified pooled analysis difference in response rates was analyzed using the cochran-mantel-haenszel test stratified by region (north america, europe, australia, and asia) and patients who used rescue medication (mostly tcs) were considered non-responders ● two post hoc analyses using kaplan-meier estimates assessed the time to relapse of iga 0/1 and easi-75 response during maintenance treatment relapse was defined as transfer to open-label treatment, rescue medication use, or discontinuation of treatment (due to lack of efficacy or adverse event [ae] or for other reasons, where lack of efficacy could not be excluded) ● both time to iga 0/1 or easi-75 response in the open-label group was assessed using aalen johansen estimator of cumulative incidence for each response type safety ● aes were assessed at each visit during both the initial 16-week treatment period and during the maintenance period conclusions ● a large proportion of initial iga 0/1 or easi-75 responders at week 16 maintained response with continued tralokinumab q2w or q4w dosing during the 36-week maintenance period, without the use of rescue medication including tcs ● the time to relapse during the maintenance period was longer for both tralokinumab q2w and q4w patients, compared to patients re-randomized to placebo patients who achieved the very stringent target of iga 0/1 had a robust response and experienced the longest times to relapse a step down in tralokinumab dosage to q4w may be an option for some patients achieving clear or almost clear skin with initial q2w dosing ● a substantial proportion of patients not achieving easi-75 or iga-0/1 at week 16 met these outcomes with continued tralokinumab q2w therapy beyond week 16 references 1. weidinger s, novak n. lancet. 2016;387:1109-22. 2. silverberg ji, et al. ann allergy asthma immunol. 2018;121:340-7. 3. dalgard fj, et al. j invest dermatol. 2015;135:984-91. 4. szegedi k, et al. j eur acad dermatol venereol. 2015;29:2136-44. 5. popovic b, et al. j mol biol. 2017;429:208-19. 6. furue k, et al. immunology. 2019;158:281-6. 7. tsoi lc, et al. j invest dermatol. 2019;139:1480-9. 8. bieber t. allergy. 2020;75:54-62. 9. wollenberg a, et al. br j dermatol. 2021;184:437-49. disclosures andrew blauvelt has served as a scientific adviser and/or clinical study investigator for abbvie, abcentra, aligos, almirall, amgen, arcutis, arena, athenex, boehringer ingelheim, bristol-myers squibb, dermavant, eli lilly, evommune, forte, galderma, incyte, janssen, landos, leo pharma, novartis, pfizer, rapt, regeneron, sanofi genzyme, sun pharma, and ucb pharma andreas wollenberg has received grants, personal fees, or nonfinancial support from abbvie, almirall, beiersdorf, bioderma, chugai, galapagos, galderma, hans karrer, leo pharma, lilly, l’oreal, maruho, medimmune, novartis, pfizer, pierre fabre, regeneron, santen, and sanofi-aventis andrew pink has acted as an advisor/speaker for abbvie, almirall, janssen, la roche-posay, leo pharma, lilly, novartis, pfizer, sanofi, and ucb ketty peris reports grants and personal fees for participation in advisory boards from abbvie and galderma and personal fees for participation in advisory boards from almirall, janssen, leo pharma, lilly, novartis, pierre fabre, sanofi, and sun pharma april armstrong reports grants from for bristol-myers squibb, dermavant, dermira, eli lilly, galderma, janssen-ortho, inc., kyowa hakko kirin, leo pharma, pfizer, and ucb pharma; and has received honoraria from abbvie, boehringer ingelheim/parexel, bristol-myers squibb, dermavant, eli lilly, janssen pharmaceuticals, inc., leo pharma, modernizing medicine, novartis, ortho dermatologics, pfizer, regeneron pharmaceuticals, sanofi genzyme, and sun pharma; and has acted as a speaker for abbvie, regeneron, and sanofi genzyme lynda spelman has been a consultant, and/or scientific adviser, and/or investigator, and/or scientific officer, and/or speaker for amgen, anacor, abbvie, ascend, astellas, astrazeneca, blaze bioscience, bms, boehringer ingelheim, botanix, celgene, dermira, eli lilly, galderma, genentech, gsk, hexima, janssen, leo pharma, mayne, medimmune, merck (msd), merck-serono, novartis, otsuka, pfizer, phosphagenics, photon md, regeneron, roche, samumed, sanofi/genzyme, shr, sun pharma anz, trius, ucb, and zai lab hidehisa saeki is an advisor to leo pharma charles lynde has received honoraria or consultant fees from abbvie, amgen, bausch health, boehringer ingelheim, celgene, eli lilly, galderma, glenmark, janssen, leo pharma, novartis, pfizer, regeneron, sanofi genzyme, sun pharma, and valeant pedro herranz is a consultant/speaker/investigator for amgen, janssen, leo pharma, lilly, novartis, parexel, pfizer, and sanofi sebastian barbarot is an investigator or speaker for abbvie, janssen, leo pharma, lilly, novartis, pfizer, sanofi-genzyme, and ucb pharma eric simpson reports grants and/or personal fees from abbvie, boehringer ingelheim, celgene, dermavant, dermira, fortébio, galderma, incyte, kyowa hakko kirin, leo pharma, lilly, medimmune, menlo therapeutics, merck, novartis, ortho dermatologics, pfizer, pierre fabre dermo cosmetique, regeneron, sanofi, tioga, and valeant figure 1. ecztra 1 and 2 trial designs 3:1 randomization patients were stratified by region and baseline disease severity (iga 3 or 4) washout of tcs and other ad medication 300 mg q2w after initial loading dose (600 mg) patients with clinical response of iga 0/1 or easi-75: re-randomized 2:2:1 ecztra 1 (n=603) ecztra 2 (n=593) patients with clinical response criteria iga 0/1 or easi-75 screening initial treatment maintenance treatment ecztra 1 and ecztra 2 trial designs safety follow-up 66 weeks52 weeks16 weeks0-6 weeks tralokinumab 300 mg q2w tralokinumab 300 mg q4w patients not achieving iga 0/1 or easi-75 at 16 weeks open-label tralokinumab 300 mg q2w + optional tcs (n=686) patients not achieving iga 0/1 or easi-75 at 16 weeks open-label tralokinumab 300 mg q2w + optional tcs tralokinumab 300 mg q2w ecztra 1 (n=199) ecztra 2 (n=201) placebo q2w placebo q2w placebo q2w a b key eligibility criteria • �18 years of age • confirmed diagnosis of atopic dermatitis for �1 year • easi score �16 • iga score �3 • pruritus numeric rating scale �4 • candidates for systemic therapy due to a recent (within 1 year) history of inadequate response or intolerance to topical treatment c criteria for transfer from maintenance to open-label after week 16 iga of at least 2 and not achieving easi-75 over at least a 4-week period ie, over 3 consecutive visits iga 0 at week 16 iga of at least 3 and not achieving easi-75 over at least a 4-week period ie, over 3 consecutive visits iga 1 at week 16 not achieving easi-75 over at least a 4-week period ie, over 3 consecutive visits iga �1 at week 16 ad, atopic dermatitis; easi, eczema area and severity index; iga, investigator’s global assessment; q2w, every 2 weeks; q4w, every 4 weeks; tcs, topical corticosteroids. figure 3. time to relapse during maintenance treatment in patients achieving (a) iga 0/1 and (b) easi-75 at week 16 figure 2. maintenance of week 16 iga 0/1 and easi-75 responses at week 52 without rescue medication 0 10 20 30 40 60 80 90 50 70 100 0 10 20 30 40 60 80 90 50 70 100 0 10 20 30 40 60 80 90 50 70 100 iga 0/1a ig a 0 /1 , % tralokinumab q2w (week 0–16) tralokinumab q4w (maintenance period) re-randomization: tralokinumab q2w (week 0–16) tralokinumab q2w (maintenance period) tralokinumab q2w (week 0–16) placebo (maintenance period) tralokinumab q2w (week 0–16) tralokinumab q4w (maintenance period) re-randomization: tralokinumab q2w (week 0–16) tralokinumab q2w (maintenance period) tralokinumab q2w (week 0–16) placebo (maintenance period) tralokinumab q2w (week 0–16) tralokinumab q4w (maintenance period) re-randomization: tralokinumab q2w (week 0–16) tralokinumab q2w (maintenance period) tralokinumab q2w (week 0–16) placebo (maintenance period) q2w to q2w (n=93) q2w to q4w (n=85) q2w to placebo (n=47) easi-75b ea s i75 , % q2w to q2w (n=124) q2w to q4w (n=131) q2w to placebo (n=72) iga 0/1 or easi-75c ig a 0 /1 o r ea s i75 , % q2w to q2w (n=130) q2w to q4w (n=134) q2w to placebo (n=73) a p ro b a b ili ty o f n o r e la p se weeks since first maintenance treatment 1.0 0 16 20 24 28 32 36 40 44 48 52 tralokinumab q4w tralokinumab q2w censored placebo tralokinumab q4w tralokinumab q2w censored placebo number of subjects at risk 93 85 47 tralokinumab q2w tralokinumab q4w placebo 88 83 45 85 78 43 84 70 37 75 63 31 72 56 27 70 54 22 68 53 21 63 51 20 42 37 15 b 1.0 0 p ro b a b ili ty o f n o r e la p se weeks since first maintenance treatment easi-75 iga 0/1 16 20 24 28 32 36 40 44 48 52 number of subjects at risk 122 131 72 tralokinumab q2w tralokinumab q4w placebo 114 128 69 105 116 63 100 103 50 90 91 42 86 81 36 83 78 30 80 74 26 75 71 24 51 50 16 figure 4. time to iga 0/1 (a) or easi-75 (b) response during the open-label treatment period a treatment week iga 0/1 16 20 24 28 32 36 40 44 48 52 number of subjects at risk tralokinumab q2w + optional tcs b 1.0 0.8 0.6 0.4 0.2 0 1.0 0.8 0.6 0.4 0.2 0 treatment week easi-75 16 20 24 28 32 36 40 44 48 52 number of subjects at risk tralokinumab q2w + optional tcs 685 679 605 532 460 399 350 322 296 269 c u m u la ti ve p ro b a b ili ty o f re sp o n se c u m u la ti ve p ro b a b ili ty o f re sp o n se 661 654 490 381 295 232 193 162 132 114 analysis of patients who achieved a clinical response of (a) iga 0/1 at week 16, (b) easi-75 at week 16, (c) iga 0/1 or easi-75 at week 16 (all without rescue medication), with tralokinumab q2w and were re-randomized to receive either tralokinumab q2w, tralokinumab q4w, or placebo until week 52. patients who received rescue medication or were transferred to open-label treatment considered non-responders. patients with missing data were imputed as non-responders. differences in response rates were analyzed using the cochran-mantel-haenszel test stratified by region and study id. easi, eczema area and severity index; iga, investigator’s global assessment; q2w, every 2 weeks; q4w, every 4 weeks. analysis includes patients who achieved (a) iga 0/1 or (b) easi-75 at week 16 without rescue medication use. easi, eczema area and severity index; iga, investigator’s global assessment; q2w, every 2 weeks, q4w, every 4 weeks. analysis includes patients who completed week 16 on tralokinumab 300 mg q2w and transferred to open-label treatment with tralokinumab q2w plus optional tcs. easi, eczema area and severity index; iga, investigator’s global assessment; q2w, every 2 weeks; q4w, every 4 weeks; tcs, topical corticosteroids. characteristic all randomized (n=1596) tralokinumab q2w (n=1196) placebo (n=400) mean age, y (sd) 37.8 (14.4) 37.9 (14.2) 37.2 (14.8) male, n (%) 947 (59.3) 710 (59.4) 237 (59.3) region, n (%) north america 559 (35.0) 419 (35.0) 140 (35.0) europe 711 (44.5) 533 (44.6) 178 (44.5) australia 121 (7.6) 90 (7.5) 31 (7.8) asia 205 (12.8) 154 (12.9) 51 (12.8) mean affected bsa, % (sd) 52.9 (24.9)a 52.7 (24.8) 53.6 (25.3)j mean disease duration, y (sd) 28.2 (15.2)b 28.1 (15.2)f 28.5 (14.9)j severe disease (iga 4), n (%) 794 (49.7) 591 (49.4) 203 (50.8) mean easi (sd) 32.29 (13.97)c 32.15 (14.01)g 32.72 (13.86)k mean weekly average worst daily pruritus nrs (sd) 7.81 (1.43)d 7.79 (1.45)h 7.84 (1.37)l mean total scorad (sd) 70.39 (13.00)c 70.16 (13.19)g 71.07 (12.38)k mean dlqi (sd) 17.30 (7.08)e 17.25 (7.12)i 17.45 (6.98)m table 1. demographic and disease characteristics at baseline for all randomized patients in ecztra 1 and 2 n (%) initial treatment period (baseline to week 16) maintenance period (weeks 16 to 52) week 16 tralokinumab responders tralokinumab 300 mg q2w (n=1194) placebo (n=396) tralokinumab q2w to tralokinumab q2w (n=159) tralokinumab q2w to tralokinumab q4w (n=165) tralokinumab q2w to placebo (n=81) ≥1 ae 824 (69.0) 283 (71.5) 116 (73.0) 109 (66.1) 57 (70.4) ≥1 sae 33 (2.8) 13 (3.3) 1 (0.6) 6 (3.6) 0 (0) severity mild 673 (56.4) 204 (51.5) 102 (64.2) 94 (57.0) 44 (54.3) moderate 409 (34.3) 182 (46.0) 62 (39.0) 45 (27.3) 27 (33.3) severe 65 (5.4) 32 (8.1) 4 (2.5) 5 (3.0) 3 (3.7) ae leading to withdrawal from trial 28 (2.3) 9 (2.3) 3 (1.9) 2 (1.2) 0 (0) table 2. summary of aes in the initial and maintenance treatment periods of ecztra 1 and 2 an=1595; bn=1594; cn=1590; dn=1577; en=1572; fn=1195; gn=1192; hn=1182; in=1178; jn=399; kn=398; ln=395; mn=394 bsa, body surface area; sd, standard deviation; iga, investigator’s global assessment; easi, eczema area severity index; nrs, numeric rating scale; scorad, scoring atopic dermatitis; dlqi, disability life quality index; q2w, every 2 weeks further details of the ae profile in these populations have been reported previously.9 ae, adverse event; q2w, every 2 weeks; q4w, every 4 weeks; sae, serious adverse event. originally presented at american academy of dermatology (aad) vmx, april 23-25, 2021. microsoft word 20. 594 proof done.docx skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 101 compelling comments dermatologic etymology: what’s in a name? paul a. regan, bs1 1penn state college of medicine, hershey, pa have you ever wondered how a disease got its name? for example, why is a skin tag called an acrochordon? what does it literally mean to have a viral exanthem? why does intertrigo refer to skin folds? in the past, a familiarity with the classical languages was seen as an essential skill for practicing physicians. for medical students, learning greek and latin was highly recommended, and sometimes even a prerequisite. in medical terminology, the meaning of many anatomic descriptions and disease names can be derived from their greek and latin roots. george henry fox, an american dermatologist, published his “dermatologic etymology” in the archives of dermatology and syphilology in 1921.1 he includes a list of the greek or latin roots for many commonly used terms in dermatology. acrochordon is a combination of the greek roots ἄκρο(acro-), which means top or extremity, and χορδή (chorde), meaning string or cord. with those roots in mind, you can see how a pedunculated growth on the skin became known as an acrochordon. exanthem comes from the greek word ἐξάνθημα (exanthema), which means to bloom or flower. thus, a viral exanthem appears as a rash erupting on the skin like a blooming flower. if you can remember that intertrigo is derived from the latin roots inter, meaning between, and tritus (from terere), meaning to rub, then you will understand why intertrigo occurs in the axillae and groin. knowing the etymology of the diseases that we treat or the diagnostic descriptions that we use may facilitate a deeper meaning for the clinician and an appreciation for the history of medicine. next time you are reading about a disease or pathological finding, consider the etymology of the words and you may find them easier to understand and remember. conflict of interest disclosures: none funding: none corresponding author: paul a. regan, bs penn state college of medicine, hershey, pa email: pregan@pennstatehealth.psu.edu references: 1. fox, george henry. dermatologic etymology. arch derm syphilol. 1921;3:404-412. powerpoint presentation conclusion • the findings of this study indicate that in patients with pn, nal-er tablets, at a dose of 162 mg b.i.d., appear to have a measurable antipruritic effect for patients who successfully maintain the initial therapy for at least 10 weeks. • the significantly greater response rate for nal-er 162 mg patients who completed the full 10 weeks of double-blind treatment compared with placebo is consistent with a clinical benefit that requires compliance with the designated dosing schedule and duration. • further evaluation of nal-er, including further elucidation of its underlying mechanism of action, is thus warranted in this difficult-to-treat disease, with a larger phase 2b/3 clinical trial currently evaluating the 162 mg b.i.d. dose. efficacy and safety of oral nalbuphine extended release in prurigo nodularis: results of a phase 2, randomized, controlled trial with an open-label extension phase elke weisshaar1; thomas r. sciascia2; sonja ständer3 1occupational dermatology, department of dermatology, university hospital, heidelberg, germany; 2trevi therapeutics, new haven, ct, usa; 3department of dermatology and center for chronic pruritus, university hospital, münster, germany introduction • prurigo nodularis (pn) is a relatively rare, intensely pruritic dermatologic disease that develops from prolonged itching and scratching, with a high associated quality-of-life impact.1 • the current guidelines for treating pn are based on empirical observations and single, randomized, controlled trials.2,3,4 • therapies such as calcineurin inhibitors, topical steroids, and systemic antihistamines have limited data to support their use. • the synthetic opioid nalbuphine, a dual-acting µ antagonist and  agonist, has shown efficacy in morphine-induced pruritus and uremic pruritus,5,6 but an evaluation of the efficacy and safety of nalbuphine in pn is currently lacking. methods • patients with moderate-to-severe pn (pruritus duration ≥ 6 weeks) were randomized 1:1:1 to receive either nal-er 81 mg or 162 mg tablets twice-daily (b.i.d.), or placebo for 8 weeks of stable dosing following a 2-week titration period (for dose-escalation from 30 mg once-daily to the assigned target dose). • itch scores based on worst itch (wi) and average itch numerical rating scale (nrs) with 24-hour recall were collected daily by an electronic diary (diarypro®). • the primary efficacy endpoint was the proportion of patients with a ≥ 30% reduction in 7-day mean wi-nrs from baseline to week 10/last observation. • the primary safety endpoint was the incidence of opioid-type adverse events of nausea, vomiting, constipation, somnolence, sedation, dizziness, and vertigo in each treatment group. results, continued results, continued • treatment-emergent adverse events (teaes) occurred predominantly during the titration period in both studies. during double-blind, stable-dose treatment that followed titration, teae incidence was similar for both active treatment arms and placebo (table 2). • common teaes were nausea, dizziness, headache, and fatigue; the majority of these events were also considered treatment-related in all 3 arms (table 2). • in the extension study, 34 patients reported 154 teaes, including 26 patients with ≥ 1 drug-related teae. teaes included nausea (n = 9; 25.0%), and dizziness and fatigue (n = 8 for each; 22.2%). references 1. ständer hf, et al. j am acad dermatol. 2020;82:460-68. 2. tsianakas a, et al. curr probl dermatol. 2016;50:94-101. 3. weisshaar e, et al. acta derm venereol. 2019;99:469-506. 4. ständer s, et al. itch. 2020; submitted. 5. kjellberg f, tramèr mr. eur j anaesthesiol. 2001;18:346-57. 6. mathur vs, et al. am j nephrol. 2017;46:450-8. presented at the 2021 winter clinical dermatology conference–hawaii® objective • to evaluate the efficacy and safety of oral nalbuphine extended release (nal-er) tablets in a phase 2, multicenter, randomized, double-blind, placebo-controlled trial with an open-label extension phase. acknowledgment this study was funded by trevi therapeutics. the authors received writing/editorial support in the preparation of this poster provided by excerpta medica, funded by trevi therapeutics. conflicts of interest ew is an investigator in clinical trials for kiniksa, menlo therapeutics, and trevi therapeutics. trs is an employee of trevi therapeutics. sst is an investigator for dermasence, galderma, kiniksa, menlo therapeutics, trevi therapeutics, novartis, sanofi, and vanda therapeutics; a consultant and/or advisory board member for almirall, bayer, beiersdorf, bellus health, bionorica, cara therapeutics, celgene, clexio, ds biopharma, galderma, kiniksa, lilly, menlo therapeutics, novartis, pfizer, sanofi, and trevi therapeutics. table 2. treatment-emergent adverse events (safety population) adverse event, n (%) nal-er placebo (n = 22)81 mg (n = 22) 162 mg (n = 18) teae 17 (77.3) 16 (88.9) 14 (63.6) serious teae 1 (4.5) 0 (0) 1 (4.5) related teae 12 (54.5) 13 (72.2) 8 (36.4) teae onset during titration period 16 (72.7) 13 (72.2) 10 (45.5) fixed dose period 8 (36.4) 8 (44.4) 8 (36.4) washout/safety 6 (27.3) 6 (33.3) 4 (18.2) teae with > 15% incidence overall by system organ class / preferred term gastrointestinal disorders nausea 4 (18.2) 7 (38.9) 1 (4.5) general disorders and administration-site conditions fatigue 5 (22.7) 2 (11.1) 0 nervous system disorders dizziness 5 (22.7) 7 (38.9) 1 (4.5) headache 6 (27.3) 5 (27.8) 2 (9.1) table 1. primary and secondary efficacy outcomes (mitt) of responders endpoints, n/n (%) nal-er placebo 81 mg 162 mg primary endpoints ≥ 30% reduction in 7-day wi intensity nrs vs baseline last observation 6/22 (27.3) 8/18 (44.4) 8/22 (36.4) completers 6/18 (33.3) 8/12 (66.7) 8/20 (40.0) ≥ 50% reduction in 7-day wi intensity nrs vs baseline last observation 3/22 (13.6) 6/18 (33.3) 4/22 (18.2) completers 3/18 (16.7) 6/12 (50.0)* 4/20 (20.0) secondary endpoints ≥ 30% reduction in 7-day average itch intensity nrs vs baseline last observation 11/22 (50.0) 11/18 (61.1) 9/22 (40.9) completers 11/18 (61.1) 10/12 (83.3)* 8/20 (40.0) ≥ 50% reduction in 7-day average itch intensity nrs vs baseline last observation 8/22 (36.4) 6/18 (33.3) 4/22 (18.2) completers 8/18 (44.4) 6/12 (50.0)* 4/20 (20.0) study completers were analyzed as a subset of all mitt. completers are patients who completed week 10 of the study and attended visit 5. *p ≤ 0.05 vs placebo. mitt, modified intent-to-treat. results • of 62 treated patients, 50 completed 10 weeks of treatment. the primary efficacy endpoint of percentage of responders with ≥ 30% reduction from baseline in 7-day wi intensity was not significant for the primary modified intent-to-treat analysis but, was significant for nal-er 162 mg (66.7%) compared with placebo (40.0%; p = 0.026) among completers (table 1). skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 353 brief articles pediatric alopecia areata in three siblings adele shenoy, ba1, carey kim, md1, alice gottlieb, md, phd2 1department of dermatology, new york medical college, ny, ny 2department of dermatology, icahn school of medicine at mount sinai, ny, ny alopecia areata has a lifetime risk of approximately 2% and presents with a wide spectrum of hair loss ranging from patchy loss on the scalp, full hair loss of the head, or complete hair loss of the body. aa is the result of an autoimmune attack of hair follicles by predominately cd8+ t-cells leading to an inflammatory state.1 prior studies have shown the lifetime risk of siblings to be 7.1% and the concordance rate among identical twins to be only 55%. 2,3 these studies suggest that there is a likely interaction between genes and the environment in the development of aa within families. although familial aa has been studied, there are few reports of concurrent pediatric aa in siblings. 4,5,6 a 7 year-old girl with history of asthma presented with a 4-month history of progressive patchy hair loss of the scalp and eyebrows associated with itching and erythema. prior to the hair loss, she had a self-resolving fever, headache, and postauricular swelling for approximately 2 weeks. she had no prior medication use or other medical history, including thyroid disease, vitiligo, diabetes mellitus, and psychiatric symptoms. physical exam showed tightly braided hair and a plaque with white scales in the occipital and frontal regions of the scalp. she had loss of the bilateral eyebrows with mild hypopigmentation and normal eyelashes and nails (figure 1). she was instructed to remove the braids and was given griseofulvin and ketoconazole shampoo for a diagnosis of tinea capitis. on six-week follow-up, the mother had shaved the patient’s hair and the pruritus, erythema, and scaling had resolved. however, the patchy hair loss of the scalp and eyebrows remained (figure 2). a biopsy of the scalp showed an increased number of hairs in catagen phase with peribulbar lymphocytic alopecia areata (aa) is a common non-scarring inflammatory hair loss disorder with an incompletely defined pathogenesis. prior studies have examined familial expression of aa, but few cases in the literature describe concurrent presentation amongst siblings. our case demonstrates the complex interplay between genetic and environmental factors in the development of alopecia areata within families. introduction case 1 abstract skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 354 infiltrate consistent with aa, and clobetasol lotion was started. the younger sibling of case 1 is a 21-month old male with history of asthma who presented in 2015 with complete hair loss of the scalp for 2 months. there were no exacerbating factors or illness prior to onset. physical exam of the scalp showed diffuse black vellus hairs and intact follicles without erythema, scaling, or scarring, and intact eyebrows, eyelashes, and nails. throughout the next two years, high potency topical corticosteroids and intralesional triamcinolone injections were used on the scalp. during this time, he was treated for superimposed tinea capitis which resolved with griseofulvin therapy. on presentation in 2018, he had patchy regrowth of hair in the parietal and occipital regions and a salt score of 30% (figure 3). the 10 year-old brother had history of asthma and onset of patchy hair loss of the scalp at age 6, and was diagnosed with aa at an outside clinic. the patient was started on a topical steroid and had complete regrowth after 2 years without recurrence. there was no history of hair loss or additional medical history in the extended members of the family. the parents immigrated from gambia and all three children were born in the united states. given the patients’ concurrent presentation of erythema and scaling which resolved with griseofulvin, our patients likely had tinea capitis superimposed on alopecia areata. the 7 year-old female patient also likely had traction alopecia secondary to her tightlybraided hair. case 2 case 3 figure 1. 7-year old female with complete loss of eyebrows with hypopigmentation and patchy hair loss of the scalp with some remaining tight braids intact. skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 355 figure 2. at follow-up six weeks later, she still had complete loss of eyebrows with hypopigmentation and hair loss of the posterior and temporal-parietal scalp. figure 3. in 2018, the patient from case 2 presented with patchy alopecia of the scalp in the frontal, temporal, and occipital regions despite high potency topical corticosteroid therapy. skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 356 our unique case of pediatric alopecia areata in three siblings demonstrates the complex interaction between genetics and the environment in the pathogenesis of aa within families. the children are first-degree relatives and likely inherited similar genetic susceptibilities to aa. they also lived in the same household, and had varying clinical presentation, age of onset, and response to therapy. this suggests an environmental component, as well. the genetics of aa is complex, and genome-wide association studies have shown that aa is associated with multiple genes largely participating in the regulation of the immune system. examples include human leukocyte antigen (hla) alleles dqbi*0301 and drb1*1104, as well as ulbp. ulbp participates in stress responses involving natural killer cells and t-lymphocytes and is up-regulated in aa lesions. 7 similarly, jak kinases influence gene expression of interferon gamma and its related cytokines that are present in lesional skin, providing the rationale for the successful clinical trials of jak inhibitors in aa. 1,8 our patients may benefit from therapy with these jak inhibitors in the future. whether these genes influenced the age of onset and severity of aa in our patients is unclear. studies of familial alopecia areata have shown that the age of onset and severity of aa were similar in patients with or without family history of the disease, but that there was a positive correlation between age of onset in patients and their firstdegree relatives. 3 similarly, whether genes are implicated in the comorbidity of asthma and aa in the three siblings remains uncertain. in a study examining 2115 patients with aa, atopy was found in 38.2%. 9 the siblings had differential response to topical corticosteroids, and only one of the three had a prior febrile illness. differences in therapeutic response and disease triggers suggest that inherited genes alone do not entirely account for aa within families. one possible explanation for these differences is the association of epigenetic changes including histone modifications and methylation of dna with aa.10 another potential explanation is that environmental factors such as hormone balance, infection, and psychological stress contributed to variations in clinical presentation.11 our case of pediatric alopecia areata in three siblings demonstrates the complex role of genetics and its interaction with environmental factors in families with aa. additional research into its pathogenesis and inheritance is required to further elucidate the variation in the presentation and progression of aa. conflict of interest disclosures: none funding: none corresponding author: adele shenoy, ba new york medical college department of dermatology metropolitan hospital center 1901 first avenue room 1208 new york, ny, 10029 914-594-5900 adele_shenoy@nymc.edu references: 1. xing l, dai z, jabbari a, et al. alopecia areata is driven by cytotoxic t lymphocytes and is reversed by jak inhibition. nat med. 2014;20(9):1043-1049. discussion mailto:adele_shenoy@nymc.edu skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 357 2. jackow c, puffer n, hordinsky m, nelson j, tarrand j, duvic m. alopecia areata and cytomegalovirus infection in twins: genes versus environment? j am acad dermatol. 1998;38(3):418-425. 3. blaumeiser b, van der goot i, fimmers r, et al. familial aggregation of alopecia areata. j am acad dermatol. 2006;54(4):627-632. 4. menon r, kiran c. concomitant presentation of alopecia areata in siblings: a rare occurrence. int j trichology. 2012;4(2):86-88. 5. mitra d, agarwal r, chopra a, kandpal r. rare presentation of alopecia universalis congenita and twenty-nail dystrophy in siblings. int j trichology. 2017;9(2):63-66. 6. mohanty s, rohatgi pc, manchanda k. coexistent presence of alopecia areata in siblings: a rare presentation. int j trichology. 2014;6(2):67-68. 7. petukhova l, duvic m, hordinsky m, et al. genome-wide association study in alopecia areata implicates both innate and adaptive immunity. nature. 2010;466(7302):113-117. 8. liu ly, craiglow bg, dai f, king ba. tofacitinib for the treatment of severe alopecia areata and variants: a study of 90 patients. j am acad dermatol. 2017;76(1):22-28. 9. huang kp, mullangi s, guo y, qureshi aa. autoimmune, atopic, and mental health comorbid conditions associated with alopecia areata in the united states. jama dermatol. 2013;149(7):789794. 10. zhao m, liang g, wu x, et al. abnormal epigenetic modifications in peripheral blood mononuclear cells from patients with alopecia areata. br j dermatol. 2012;166(2):226-273. 11. strazzulla lc, wang ehc, avila l, et al. alopecia areata: disease characteristics, clinical evaluation, and new perspectives on pathogenesis. j am acad dermatol. 2018;78(1):1-12. skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 704 compelling comments social media and skin cancer prevention: a promising platform for education among adolescents and young adults mary cavanagh, bs1, brinda chellappan, md2 1 texas tech university health sciences center el paso, paul l. foster school of medicine, el paso, tx 2 orange park medical center, orange park, fl with an increase in social media usage, patients and healthcare professionals have taken to platforms like instagram, twitter, and tiktok to promote awareness about several diseases and health conditions. 1 in the united states, 39% of adults turn to social media for health information.1 the rising incidence of skin cancer allows for the novel use of social media to encourage skin cancer education and prevention. 1 this platform may specifically benefit adolescents and young adults, as melanoma has been identified as the third most common cancer among patients aged 15-39.1 instagram is a popular social media platform which garners 1 billion users each month, 90% of which are less than 35 years of age1. instagram was identified as the social media platform with the highest number of postings about skin cancer awareness. 1 one study examining instagram posts related to skin cancer found that content mostly focused on skin cancer treatment, the impact of sun exposure, and specific preventative measures such as the use of sunscreen and protective gear.2 nearly one-quarter of the posts discussed the abcdes of melanoma.2 studies have shown an increase in sunscreen usage among middle and high school students in recent years. among u.s. adolescents in grades 6-12, average mean sunscreen usage increased by 4% for every consecutive year between 2007 and 2019.3 these findings are reassuring when compared to 1999-2009, which saw an overall decrease in sunscreen usage among adolescents.3 authors cited increased skin cancer prevention content on social media as a potential explanation for the increased sunscreen use among teens.3 dermatologists, healthcare professionals, and medical societies, like the american academy of dermatology, have successfully utilized social media for patient education. these social media educators should consider creating content specifically for adolescents and young adults to highlight techniques for skin cancer prevention and identification. conflict of interest disclosures: this research was supported in part by hca healthcare and/or an hca healthcare affiliated entity. the views expressed in this publication represent those of the authors and do not necessarily represent the official views of hca healthcare or any of its affiliated entities. funding: none corresponding author: mary cavanagh, bs skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 705 texas tech university health sciences center paul l. foster school of medicine el paso phone: (512) 367-9502 email: mary.cavanagh@ttuhsc.edu references: 1. de la garza h, maymone mbc, vashi na. impact of social media on skin cancer prevention. int j environ res public health. 2021;18(9):5002. published 2021 may 9. doi:10.3390/ijerph18095002 2. basch c, hillyer g. skin cancer on instagram: implications for adolescents and young adults. int j adolesc med health. 2020;0(0). doi:10.1515/ijamh-2019-0218 3. rajagopal g, talluri r, chuy vs, cheng al, dall l. trends in sunscreen use among us middle and high school students, 2007-2019. cureus. 2021;13(7):e16468. published 2021 jul 18. doi:10.7759/cureus.16468 background ■ biologic therapies are commonly used in the united states (us) to treat moderate to severe plaque psoriasis, a chronic, relapsing, inflammatory immune-mediated skin disease that has been shown to have a negative impact on patients’ productivity and quality of life and to incur substantial medical care costs (vanderpuye-orgle et al., 2015; brezinski et al., 2015; jacobs et al., 2011). ■ guselkumab is an anti-interleukin-23 monoclonal antibody administered by subcutaneous injection that is indicated for the treatment of moderate to severe plaque psoriasis. ■ certolizumab pegol is monoclonal antibody to tnf-alpha admistered by subcutaneous injection that is indicated for the treatment of moderate to severe plaque psoriasis ■ efficacy data through week 16 from clinical trials for both products are available (voyage 1 and voyage 2 for guselkumab [blauvelt et al., reich et al., 2017] and cimpact for certolizumab pegol [lebwohl et al., 2018] ■ understanding the relative value of new treatments for moderate to severe plaque psoriasis is important for insurers, health care providers, patients, and government health authorities. objective ■ to estimate the cost per responder in the us for guselkumab relative to certolizumab pegol in the first year (induction year) of treatment based on indirect comparison of efficacy results from pivotal clinical trials (voyage 1 for guselkumab and cimpact for certolizumab pegol). methods ■ the calculation used to estimate the cost per responder was: ■ cost per responder = (per unit drug costs) × (# of doses per 52 weeks) percentage of patients with a response at 16 weeks (voyage 1 or cimpact) ■ dosing was based on the food and drug administration label in the first year, and the number of doses was based on a full, 52-week year for both products as shown in table 1. table 1. dosing and pricing inputs for guselkumab and certolizumab pegola,b biologic dosing pricing number of doses in 52 weeks induction year (maintenance year) guselkumab 100 mg administered by subcutaneous injection at week 0, week 4, and every 8 weeks thereafter wac per 100 mg: $10,158.52 8 (6) certolizumab pegol 400 mg (given as 2 subcutaneous injections of 200 mg each) every other week. for some patients (with body weight ≤ 90 kg), a dose of 400 mg (given as 2 subcutaneous injections of 200 mg each) initially and at weeks 2 and 4, followed by 200 mg every other week may be considered. wac per 400 mg: $4,044.32 26 (400 mg injections) wac = wholesale acquisition cost. 1the wac is a published list price. wac does not contain any discounts, price concessions, or charge-backs extended to wholesalers or other end users. wac is not intended to represent an actual sales price to customers. wholesalers and distributors determine the actual sales price to end-user customers. 2wac as of june 2018. 3a dose of 200 mg is a prescribing option for certolizumab pegol but the cost per responder analysis is based on the efficacy data for the recommended 400 mg dose. ■ voyage 1 (a randomized, double-blind, placeboand active-controlled clinical trial; blauvelt et al., 2017) and cimpact (a randomized, double-blind, placebo and multiple-dose [400 mg, 200 mg] controlled trial; lebwohl et al., 2018) were both phase 3 trials that enrolled patients with moderate to severe plaque psoriasis with similar levels of disease severity (mean psoriasis area and severity index [pasi] score 22.1 for voyage 1, 20.8 for cimpact [400 mg dose]) and disease duration (mean 17.9 years for voyage 1, 17.8 years for cimpact [300 mg dose]) at baseline. ■ pasi 75 and pasi 90 16-week efficacy results were extrapolated to 52 weeks (assumed unchanged) and used in the induction year cost-per-responder calculation — due to substantial differences in trial design and methodology for reporting results (cimpact trial used logistic regression and responder analysis beyond week 16 while voyage 1 used non-responder imputation), week 16 pasi 90 response rates were used from each trial. response rates were assumed to be unchanged from week 16 and extrapolated to week 52; however, this may under represent guselkumab pasi 90 results, given that response rates increased past week 16 in voyage 1. ■ a sensitivity analysis was conducted for patients achieving a pasi 75 response at 48 weeks. due to differences in the way that results were reported between the two trials, the number of patients who had a response at 16 weeks was multiplied by the percentage of patients that continued to have a pasi 75 response at 48 weeks for certolizumab pegol (cimpact trial). this was compared to the percentage of patients with a pasi 75 response at 48 weeks for guselkumab (voyage 1). — this methodology could not be conducted for pasi 90 due to the difference in data reporting from the cimpact trial (the percentage of patients with a pasi 90 response at 16 weeks who continued to have a pasi 90 response at 48 weeks was unavailable). results ■ the first-year wac costs (induction) were $81,268.16 (8 × $10,158.52) for guselkumab and $105,152.32 (26 × $4,044.32) for 400mg certolizumab pegol. ■ figure 1 shows the percentage of patients in the voyage 1 and cimpact trials reaching a pasi 90 response at 16 weeks (73.3% for guselkumab and 49.1% for certolizumab pegol), and the percentage of patients reaching a pasi 75 response at 16 weeks (91.2% for guselkumab and 74.7% for certolizumab pegol) figure 1. percentage of patients reaching pasi 75 and pasi 90 response at 16 weeks p e rc e n t o f p a ti e n ts r e a c h in g p a s i r e sp o n se 91.2% 73.3%74.7% 49.1% 0.00% 10.00% 20.00% 30.00% 40.00% 50.00% 60.00% 70.00% 80.00% 90.00% 100.00% pasi 75 ef�cacy at 16 weeks pasi 90 ef�cacy at 16 weeks guselkumab (100mg) certolizumab pegol (400mg q2w) ■ figure 2 shows the cost-per-responder estimates for the two drugs pasi 75 and pasi 90 response rates in the induction year. ■ figure 3 shows results of the sensitivity analysis for the percentage of patients in the voyage 1 and cimpact trials reaching a pasi 75 response at 48 weeks (87.8% for guselkumab and 73.2% for certolizumab pegol) ■ for all response rates for both the base case induction year and the sensitivity analysis, the cost per responder was lower for guselkumab compared to certolizumab pegol (figures 2 and 4). figure 2. cost per responder for pasi 75 and pasi 90 response levels, induction year guselkumab (100mg) certolizumab pegol (400mg q2w) $89,109.82 $110,870.61 $140,766.16 $214,159.51 $0.00 $50,000.00 $100,000.00 $150,000.00 $200,000.00 $250,000.00 cost per pasi 75 responder 48 weeks cost per pasi 90 responder 48 weeks figure 3. sensitivity analysis: percentage of patients reaching pasi 75 at 48 weeks figure 3 p e rc e n ta g e o f p a ti e n ts r e a c h in g p a s i 7 5 r e sp o n se 87.8% 73.2% 0.00% 10.00% 20.00% 30.00% 40.00% 50.00% 60.00% 70.00% 80.00% 90.00% 100.00% sensitivity analysis pasi 75 ef�cacy at 48 weeks guselkumab (100mg) certolizumab pegol (400mg q2w) figure 4. sensitivity analysis: cost per responder for pasi 75, induction year figure 4 $92,560.55 $143,638.94 $0.00 $40,000.00 $60,000.00 $80,000.00 $120,000.00 $140,000.00 $160,000.00 sensitivity analysis pasi 75 ef�cacy at 48 weeks guselkumab (100mg) certolizumab pegol (400mg q2w) limitations ■ perfect adherence was assumed for purposes of costing. ■ a formal indirect comparison was not conducted; however, enrolled population characteristics appear to be similar between the two trials. ■ response rates were not adjusted for placebo response, as placebo response rates were similar and low in both trials. ■ efficacy results in the base case were assumed to be unchanged from 16 weeks to 52 weeks. ■ a cost per responder analysis based on pasi 100 outcomes was not included as pasi 100 results were not available in the published cimpact trial results. ■ all certolizumab pegol week 16 pasi 75 and pasi 90 response rates from cimpact were analyzed using a logistic regression model with fixed effects for treatment, region, and prior biologic exposure (yes/no). results beyond week 16 were not used because they were based on a responder analysis and thus may appear inflated relative to results from the guselkumab trial. conclusions ■ this analysis based on indirect comparison of efficacy data from the voyage 1 and cimpact trials, demonstrates that guselkumab is a more cost-effective therapy than certolizumab pegol, with a lower cost per responder for achieving pasi 75 and pasi 90 responses in the first year of treatment among patients with moderate to severe plaque psoriasis. references 1. blauvelt a, papp ka, griffiths cem, randazzo b, wasfi y, shen y-k, li s, kimball ab. efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the continuous treatment of patients with moderate to severe psoriasis: results from the phase iii, double-blinded, placeboand active comparator-controlled voyage 1 trial. j am acad dermatol. 2017;76:405-17. 2. brezinski ea, dhillon js, armstrong aw. economic burden of psoriasis in the united states: a systematic review. jama dermatol. 2015;151:651-8. 3. jacobs p, bissonnette r, guenther lc. socioeconomic burden of immune-mediated inflammatory diseases – focusing on work productivity and disability. j rheumatol suppl. 2011;88:55-61. 4. lewbwohl m, blauvelt a, paul c, sofen h, weglowska j, piguet v, burge d, rolleri r, drew j, peterson l, augustin m. certolizumab pegol for the treatment of chronic plaque psoriasis: results through 48 weeks of a phase 3, multicenter, randomized, doubleblind, etanercept-and placebo-controlled study (cimpact). j am acad dermatol. 2018;79:266-276. 5. reich k, armstrong aw, foley p, song m, wasfi y, randazzo b, li s, shen yk, gordon kb. efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the treatment of patients with moderate to severe psoriasis with randomized withdrawal and retreatment: results from the phase iii, double blind, placeboand active comparatorcontrolled voyage 2 trial. j am acad dermatol. 2017;76:418-431. 6. vanderpuye-orgle, zhao y, lu j, shrestha a, sexton a, seabury s, lebwohl m. evaluating the burden of psoriasis in the united states. j am acad dermatol. 2015;72:961-7. contact information amanda teeple, mph manager, dermatology, immunology health economics and outcomes research janssen scientific affairs, llc, horsham, pa e-mail: ateeple@its.jnj.com this analysis was supported by janssen scientific affairs, llc. cost per responder analysis of guselkumab versus certolizumab pegol using efficacy results from pivotal clinical trials in patients with moderate to severe plaque psoriasis a. teeple, mph; e. muser, pharmd, mph janssen scientific affairs, llc, horsham, pa skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 660 covid concepts pemphigus foliaceous after covid-19 infection and bamlanivimab infusion katelyn urban, do1, rachel l. giesey, do2, gregory r. delost, do3 1 university hospitals regionals, richmond heights, oh 2 ohio university heritage college of osteopathic medicine, athens, oh 3 apex dermatology and skin surgery center, mayfield heights, oh to the authors’ knowledge, this is the first report of pemphigus foliaceous (pf) in the setting of covid-19 infection and subsequent treatment with bamlanivimab. bamlanivimab was previously granted emergency use authorization for administration as a single 700-mg iv infusion after a positive covid-19 test result and within 10 days from symptom onset. bamlanivimab binds to the spike protein of sars-cov-2 and blocks attachment to the human ace2 receptor.1 a 66-year-old male presented to the dermatology clinic with a cutaneous eruption of 3 months duration which began after receiving monoclonal antibody bamlanivimab infusion for a diagnosis of covid-19. he did not require hospital admission or home oxygen therapy after the initial diagnosis and recovered completely from the covid-19 infection without sequela. his current medications include lisinopril, rivaroxaban, and metoprolol succinate er for which he had been taking for years prior. physical examination revealed numerous well-demarcated erythematous crusted plaques with “cornflake” scale involving the central face, chest, abdomen, and back in a predominantly seborrheic distribution (figure 1 and 2). a perilesional biopsy revealed subcorneal acantholysis in the granular layer (figure 3 and 4). direct immunofluorescence (dif) revealed cell surface deposits of igg throughout the epidermis confirming the diagnosis of pemphigus foliaceous (pf). he achieved full resolution after 4 doses of the anti-cd-20 antibody, rituximab. abstract we report a case of pemphigus foliaceous (pf) in the setting of bamlanivimab, a novel monoclonal antibody for the treatment of covid-19. pf is a rare autoimmune blistering disease caused by autoantibodies directed against desmoglein-1 (dsg1). drugs and viruses have been implicated as inciting factors of pemphigus in predisposed patients. given the current pandemic, the presentation of pf following covid-19 infection and bamlanivimab infusion is of special interest and further investigation may be warranted. introduction case report skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 661 figure 1. figure 2. pf is a rare immunobullous disease caused by a production of igg autoantibodies directed against the intercellular adhesion protein, dsg1.2 dsg1 autoantibodies cause separation of keratinocytes at the granular layer of the epidermis producing fragile subcorneal blisters leading to erosive lesions.2,3 in contrast to pemphigus vulgaris, mucosal surfaces are spared in pf as there is an absence of desmoglein-3 autoantibodies.4 histology in pf may be nonspecific because the epidermis has a normal appearance if the thin blister has already detached. dif reveals intercellular igg deposition within the epidermis, with the most intense staining in the upper epidermis. several pathways leading to acantholysis have been described including biochemical modification of antigens and indirect mechanisms that alter immune response.5 the literature classically divides drug-related pemphigus based on chemical structure: thiol drugs, phenolic drugs, and nonthiol/phenolic drugs. thiol drugs are thought to disturb cell adhesion by changing the antigenic conformation of desmoglein, inhibiting enzymes that cause keratinocyte aggregation, and activating enzymes that cause keratinocyte disaggregation.5,6 phenolic drugs trigger release of cytokines that activate proteases resulting in acantholysis.6 non-thiol/phenolic drugs may cause pemphigus through various mechanisms such as over-activation of the immune system.5 pf is the most common variant of druginduced pemphigus when caused by thiol containing drugs.7 although this patient is taking lisinopril, which contains an amide group, drug-induced pemphigus is more rare among angiotensin converting enzyme inhibitors other than captopril. additionally, discussion skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 662 figure 3. figure 4. metoprolol could be considered as a possible inciting drug as there are reports of beta-blockers causing drug-induced pemphigus.7 bamlanivimab is favored as the most likely inciting agent in this case based on timeline of disease presentation. a review of 170 drug-induced pemphigus cases found that patients developed pemphigus within a mean of 154.27 days.8 the patient had been taking metoprolol and lisinopril for years prior. in addition, the patient continues to take metoprolol and lisinopril and has remained clear after treatment with rituximab. we hypothesize that bamlanivimab caused pf through an indirect immune mechanism to activate autoantibodies against dsg1, although the exact mechanism of acantholysis remains to be determined. previous case studies have reported viral infection, often herpesviruses, as an inciting factor in the development of pemphigus and thus, a paraviral eruption is also considered for the cause of the presenting pf.9 covid19 infection decreases the amount of ace2 and alters the renin-angiotensin system, which plays a role in keratinocyte differentiation.10 the release of cytokines in the infection itself may set the stage for autoimmunity in a genetically predisposed individual. controversy and difficulty in discerning the triggering event in pemphigus as viral infection, subsequent treatment intervention, or the combinations of both exists.9 nonetheless, sars-cov-2 and bamlanivimab may both be considered as possible implications in the development of pf. a previous case report described bullous pemphigoid (bp) in a patient admitted to the intensive care unit with covid-19 infection, in which virus and druginduced bp were considered as possible precipitating factors.11 further reports and investigation will help determine the causal relationship and clarify possible adverse drug reactions. full recovery from active infection with covid-19 is prudent before considering treatment of pf with rituximab. patients with autoimmune bullous disease taking rituximab have developed more severe covid-19 infection compared to the healthy population, possibly due to higher levels of il-6.12 skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 663 further reports and investigation will help determine the causal relationship and clarify possible adverse drug reactions. full recovery from active infection with covid19 is prudent before considering treatment of pf with rituximab. conflict of interest disclosures: none funding: none corresponding author: katelyn urban, do university hospitals regionals 27100 chardon rd richmond heights, oh 44143 email: katelyn.urban@uhhospitals.org references: 1. an eua for bamlanivimab-a monoclonal antibody for covid-19. jama. 2021 mar 2;325(9):880-881. 2. schmidt e, kasperkiewicz m, joly p. pemphigus. lancet. 2019 sep 7;394(10201):882-894. 3. james ka, culton da, diaz la. diagnosis and clinical features of pemphigus foliaceus. dermatol clin. 2011;29(3):405-viii. 4. melchionda v, harman ke. pemphigus vulgaris and pemphigus foliaceus: an overview of the clinical presentation, investigations and management. clin exp dermatol. 2019 oct;44(7):740-746. 5. palleria c, bennardo l, dastoli s, iannone lf, silvestri m, manti a, nisticò sp, russo e, de sarro g. angiotensin-converting-enzyme inhibitors and angiotensin ii receptor blockers induced pemphigus: a case series and literature review. dermatol ther. 2019 jan;32(1):e12748. 6. brenner s, goldberg i. drug-induced pemphigus. clin dermatol. 2011 julaug;29(4):455-7. 7. giménez-garcía and nuñez-cabezón. valsartan/hydrochlorothiazide induced pemphigus foliaceus. int j aller medications 2016;2:012. 8. ghaedi f, etesami i, aryanian z, et al. druginduced pemphigus: a systematic review of 170 patients. int immunopharmacol. 2021;92:107299. 9. ruocco e, wolf r, ruocco v, brunetti g, romano f, lo schiavo a. pemphigus: associations and management guidelines: facts and controversies. clin dermatol. 2013 julaug;31(4):382-390. 10. munavalli gg, knutsen-larson s, lupo mp, geronemus rg. oral angiotensin-converting enzyme inhibitors for treatment of delayed inflammatory reaction to dermal hyaluronic acid fillers following covid-19 vaccination-a model for inhibition of angiotensin ii-induced cutaneous inflammation. jaad case rep. 2021 apr;10:6368. 11. kim, a., khan, m., lin, a., wang, h., siegel, l., & rozenberg, s. (2021). new bullous eruptions in a covid-19 positive patient in an intensive care unit. skin the journal of cutaneous medicine, 5(3), 278–282 12. beyzaee am, rahmatpour rokni g, patil a, goldust m. rituximab as the treatment of pemphigus vulgaris in the covid-19 pandemic era: a narrative review. dermatol ther. 2021;34(1):e14405. conclusion mailto:katelyn.urban@uhhospitals.org skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 131 rising derm stars® effect of suture spacing on wound cosmesis karin eshagh, md1 1department of dermatology, uc davis medical center, sacramento, ca background: sutures are the standard of care in repairing cutaneous wounds. most surgical reconstructions following mohs micrographic surgery and standard surgical excisions require two layers of sutures: a deep layer and a top layer. some surgeons feel the need to place many deep sutures in order to reduce tension on the sutures and hence decrease the chance of wound separation and dehiscence. however, there are other surgeons who feel that deep sutures are only required in areas of high tension and that a higher number of deep sutures increases the risk of a spitting suture which leads to patient anxiety and poor wound cosmesis. thus, it is important to understand if an increased number of subdermal sutures is actually beneficial in terms of wound cosmesis. to our knowledge, there are no studies published on the effect of subdermal suture spacing on wound cosmesis. objective: to determine whether the spacing between subdermal interrupted sutures during repair of linear cutaneous surgery wounds affects scar cosmesis. in other words, the goal was to determine which of the following yields a more cosmetically appealing scar: many closely approximated subdermal sutures or fewer, more widely spaced subdermal sutures. the study specifically compared the effects of one versus two centimeter spacing between sutures. methods: 50 patients were enrolled in a randomized clinical trial using a split wound model, where half of the wound was repaired with sutures spaced two centimeters apart and the other half was repaired with sutures spaced one centimeter apart. both the physician and patient were blinded as to which side received which treatment. threemonths post-surgery, the scar was evaluated via posas: the patient and observer scar assessment scale, a validated scar instrument. results: no statistically significant difference seen between 1 cm spacing versus 2 cm spacing of subdermal sutures in preliminary analysis. limitations: our sample size was only 50 patients. future studies could examine larger populations. conclusion: suture spacing has no effect on wound cosmesis. thus, placing fewer and more widely spaced sutures is more time efficient. introduction/objective ■ guselkumab is a fully human monoclonal antibody that binds and blocks interleukin-23 ■ voyage 1 is a phase 3, double-blind, placeboand active comparator-controlled trial that showed significantly higher proportions of patients with moderate to severe plaque psoriasis achieving several outcome measures, including psoriasis area and severity index (pasi) 90 response and investigator’s global assessment (iga) of cleared (0) or minimal (1) scores, with guselkumab versus placebo at week 16 and guselkumab versus adalimumab at week 24.1 ■ study results through up to 3 years of continuous treatment with guselkumab were examined methods ■ in voyage 1 (n=837), patients were randomized as follows (figure 1): — guselkumab 100 mg administered by subcutaneous (sc) injection at weeks 0, 4, and 12, then every 8 weeks (q8wk) — placebo (pbo) at weeks 0, 4, and 12, followed by guselkumab 100 mg sc at weeks 16 and 20, then q8wk — adalimumab 80 mg sc at week 0, 40 mg at week 1, then 40 mg q2wk through week 47 — starting at week 52, all patients received open-label guselkumab 100 mg sc q8wk through week 156 ■ efficacy was assessed using prespecified analyses: non-responder imputation (nri) through week 48 (patients with missing efficacy data after application of treatment failure rules [tfr] were counted as non-responders, without regard to the reason for missing data) and tfr starting at week 52 (patients were considered non-responders after discontinuing due to lack of efficacy or worsening of psoriasis, or after use of a prohibited treatment) ■ data for patients randomized to gusekumab and for those originally randomized to placebo and then crossed over to guselkumab at week 16 were combined (guselkumab group) figure 1. voyage 1 study design through 156 weeks active-comparator period pbocontrolled guselkumab (n=329) placebo (n=174) adalimumab (n=334) pbocrossover open-label weeks 0 16 pe se 24 se 48 se 156 3 year dbl 4 r r 52 guselkumab 100 mg at weeks 0 and 4, then q8w guselkumab 100 mg at week 52, then q8w guselkumab 100 mg at weeks 16 and 20, then q8w adalimumab 80 mg at week 0, 40 mg at week 1, then q2w = randomization pe = primary endpoint q2w = every 2 weeks q8w = every 8 weeks se = secondary endpoint placebo results figure 2. proportion of patients who achieved iga score of 0 or 1 through week 156, primary analysis† 0 20 40 60 80 100 0 4 8 12 16 20 24 28 32 36 40 44 48 52 60 68 76 84 92 100 108 116 124 132 140 148 156 guselkumab pbo→guselkumab guselkumab* adalimumab→guselkumab weeks p e rc e n ta g e o f p a ti e n ts 334 84.0 83.3 82.1 84.8 269 84.6 guselkumab n= 448 429468 pbo→gus n= guselkumab* n= ada→gus n= 174 329 165 329 278 275 60.4 80.5 89.1 †nri through week 48, then tfr beyond week 48. *includes patients randomized to guselkumab at baseline and to placebo who crossed over to guselkumab at week 16. figure 3. proportion of patients who achieved iga score of 0 through week 156, primary analysis† guselkumab pbo→guselkumab guselkumab* adalimumab→guselkumab 0 4 8 12 16 20 24 28 32 36 40 44 48 52 60 68 76 84 92 100 108 116 124 132 140 148 156 weeks p e rc e n ta g e o f p a ti e n ts guselkumab n= pbo→gus n= guselkumab* n= ada→gus n= 0 20 40 60 80 100 55.6 55.6 53.1 53.553.6 334 269 448 429468 174 329 165 329 278 275 56.4 27.3 50.5 †nri through week 48, then tfr beyond week 48. *includes patients randomized to guselkumab at baseline and to placebo who crossed over to guselkumab at week 16. figure 4. proportion of patients who achieved pasi 75 response through week 156, primary analysis† guselkumab pbo→guselkumab guselkumab* adalimumab→guselkumab 0 4 8 12 16 20 24 28 32 36 40 44 48 52 60 68 76 84 92 100 108 116 124 132 140 148 156 weeks p e rc e n ta g e o f p a ti e n ts guselkumab n= pbo→gus n= guselkumab* n= ada→gus n= 0 20 40 60 80 100 94.9 95.8 95.8 93.7 72.4 96.4 87.8 93.8 334 269 448 431468 174 329 165 329 279 275 †nri through week 48, then tfr beyond week 48. *includes patients randomized to guselkumab at baseline and to placebo who crossed over to guselkumab at week 16. figure 5. proportion of patients who achieved pasi 90 response through week 156, primary analysis† guselkumab pbo→guselkumab guselkumab* adalimumab→guselkumab 0 4 8 12 16 20 24 28 32 36 40 44 48 52 60 68 76 84 92 100 108 116 124 132 140 148 156 weeks p e rc e n ta g e o f p a ti e n ts guselkumab n= pbo→gus n= guselkumab* n= ada→gus n= 0 20 40 60 80 100 81.1 82.1 84.4 82.8 50.5 81.8 79.7 76.3 334 269 448 431468 174 329 165 329 279 275 †nri through week 48, then tfr beyond week 48. *includes patients randomized to guselkumab at baseline and to placebo who crossed over to guselkumab at week 16. figure 6. proportion of patients who achieved pasi 100 response through week 156, primary analysis† guselkumab pbo→guselkumab guselkumab* adalimumab→guselkumab 0 4 8 12 16 20 24 28 32 36 40 44 48 52 60 68 76 84 92 100 108 116 124 132 140 148 156 weeks p e rc e n ta g e o f p a ti e n ts guselkumab n= pbo→gus n= guselkumab* n= ada→gus n= 0 20 40 60 80 100 51.6 51.1 50.8 50.9 24.0 50.3 47.4 334 269 448 431468 174 329 165 329 279 275 49.1 †nri through week 48, then tfr beyond week 48. *includes patients randomized to guselkumab at baseline and to placebo who crossed over to guselkumab at week 16. figure 7. proportion of patients who achieved pasi 90 response from week 52 through week 156 (tfr, nri, observed data)* p e rc e n ta g e o f p a ti e n ts 0 20 40 60 80 100 52 60 68 76 84 92 100 108 116 124 132 140 148 156 guselkumab (tfr) guselkumab (nri) guselkumab (observed data) weeks 82.1 75.5 82.879.7 tfr: gus n=468 nri: gus n=494 observed: gus n=463 data 448 494 442 431 494 424 74.5 72.3 80.6 83.3 84.0 *includes patients randomized to guselkumab at baseline and to placebo who crossed over to guselkumab at week 16. figure 8. proportion of patients who achieved pasi 75, pasi 90, pasi 100, iga score of 0 or 1, and iga score of 0 (weeks 52-156), as observed p e rc e n ta g e o f p a ti e n ts 52 60 68 76 84 92 100 108 116 124 132 140 148 156 weeks 0 20 40 60 80 100 pasi 75 pasi 90 pasi 100 iga 0 or 1 iga 0 97.1 97.494.8 424463pasi: guselkumab* n= 83.3 84.0 80.6 51.8 51.749.7 84.4 83.4 85.5 56.3 54.054.2 iga: guselkumab* n= 463 442 422442 *includes patients randomized to guselkumab at baseline and to placebo who crossed over to guselkumab at week 16. figure 9. dlqi score of 0 or 1 at weeks 76-156 (tfr)* 75.7 75.2 74.5 74.7 0 20 40 60 80 100 guselkumab week 76 week 100 week 124 week 156 p e rc e n ta g e o f p a ti e n ts n=431n=445 n=436 n=411 dlqi=dermatology life quality index *patients with baseline dlqi score >1. weeks 76-156: includes patients randomized to guselkumab at baseline and to placebo who crossed over to guselkumab at week 16. figure 10. pssd symptom score=0 at weeks 76-156 (tfr)* 39.2 40.2 42.8 40.4 0 20 40 60 80 100 p e rc e n ta g e o f p a ti e n ts n=339n=347 n=343 n=319 guselkumab week 76 week 100 week 124 week 156 pssd=psoriasis symptom and sign diary *patients with baseline pssd symptom score >0. weeks 76-156: includes patients randomized to guselkumab at baseline and to placebo who crossed over to guselkumab at week 16. figure 11. pssd sign score=0 at weeks 76-156 (tfr)* p e rc e n ta g e o f p a ti e n ts guselkumab week 76 week 100 week 124 week 156 29.4 32.9 33.0 29.2 0 20 40 60 80 100 n=339n=347 n=343 n=319 pssd=psoriasis symptom and sign diary *patients with baseline pssd sign score >0. weeks 76-156: includes patients randomized to guselkumab at baseline and to placebo who crossed over to guselkumab at week 16. table 1. adverse events (aes) through week 48, week 100, and week 156 among patients randomized to guselkumab and placebo crossover patients guselkumab (weeks 0-48) guselkumab (weeks 0-100) guselkumab (weeks 0-156) treated patients, n 494 494 494 avg. duration of follow-up, weeks 41.6 89.4 139.2 ≥1 ae, n (%) 350 (70.9%) 395 (80.0%) 426 (86.2%) discontinued due to ≥1 ae, n (%) 10 (2.0%) 14 (2.8%) 21 (4.3%) ≥1 sae, n (%) 21 (4.3%) 45 (9.1%) 66 (13.4%) infections, n (%) 248 (50.2%) 302 (61.1%) 335 (67.8%) requiring antibiotics 79 (16.0%) 124 (25.1%) 154 (31.2%) serious infections 3 (0.6%) 6 (1.2%) 11 (2.2%) malignancies other than nmsc, n (%) 2 (0.4%) 6 (1.2%) 9 (1.8%) nmsc, n (%) 2 (0.4%) 2 (0.4%) 3 (0.6%) mace, n (%) 1 (0.2%) 1 (0.2%) 2 (0.4%) deaths, n (%) 0 2 (0.4%) 4 (0.8%) mace=major adverse cardiovascular event; nmsc=nonmelanoma skin cancer; sae=serious adverse event conclusions ■ high levels of response were stably maintained through up to 3 years of continuous guselkumab treatment in patients with moderate to severe plaque psoriasis, regardless of the data handling rules utilized ■ treatment with guselkumab was well-tolerated reference 1. blauvelt a., et al. j am acad dermatol. 2017;76(3):405-17. this poster was supported by janssen research & development, llc maintenance of response with guselkumab for up to 3 years’ treatment in the phase 3 voyage 1 trial of patients with plaque psoriasis c.e.m. griffiths,1 k.a. papp,2 m. song,3 b. randazzo,3 s. li,3 y.-k. shen,3 c. han,3 a. blauvelt4 1dermatology centre, university of manchester, manchester, uk; 2k. papp clinical research and probity research inc., waterloo, on, ca; 3janssen research & development, llc, spring house, pa, usa; 4oregon medical research center, portland, or, usa skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 496 2021 ucb® resident research competition – 3rd place original article surgeon experience level and number of mohs stages: a prospective observational study of in-training surgeons molly buckland, do1, veronica rutt, do1, adam richardson, do1, michael j. visconti, do1, kent krach, md1,2 1 department of dermatology, st. joseph mercy, ann arbor, mi 2 midwest skin cancer surgery center, clinton township, mi mohs micrographic surgery (mms) is a surgical technique utilized for the treatment of specific cutaneous malignancies. by utilizing intraoperative microscopic margin examination of frozen-section histology specimens, the tumor burden is examined in stages. this stage-based approach allows for more complete margin control and improved tissue preservation promoting a high cure rate, and improving patient satisfaction.1,2 as numerous stages may be required to achieve margin clearance, the number of stages is an objective measure of mms outcomes. factors influencing the number of stages can be oversimplified into two broad categories: tumor-specific and surgeonspecific factors.3,4,5 tumor specific factors include challenging anatomical sites with abstract background: comparisons of mohs surgeons by experience level (early-, mid-, late-career) and their respective number of stages taken during mohs have not detected any difference. however, data comparing the number of stages for attending mohs surgeons to mohs fellows is non-existent. the objective of this study was to prospectively observe and compare the mean number of mohs stages taken for attending mohs surgeons and fellows. methods: procedural data from 2,140 mohs cases over 24 months was collected and divided into an attending or fellow surgeon cohort. results: the attending cohort had a higher mean number of stages for all non-melanoma skin cancer when compared to the fellow cohort (p=0.005). the attending cohort demonstrated a higher mean number of stages for non-aggressive, non-superficial basal cell carcinoma (p<0.001), but no difference was found for other cancer subtypes. no difference was detected when comparing the two cohorts’ performance at high, medium, and low risk surgical areas. conclusion: the attending cohort had a higher mean number of stages overall for combined types of skin cancer and for non-aggressive, non-superficial basal cell carcinoma specifically when stratified by diagnosis as compared to the fellow cohort. no difference existed in the mean number of stages between the cohorts based on surgical area. introduction skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 497 minimal tissue laxity, such as the nasal tip, eyebrow, eyelid, ears. additionally, tumor histopathology, such as aggressive or superficial variants of nonmelanoma skin cancer, which can make preoperative clinical determination of tumor extent difficult, or perineural invasion, and/or deep invasion.6 intraoperative margin size decision for each stage and pre-excision curettage/debulking exemplify surgeon-specific factors.3,6 although previously hypothesized to be an important factor, the number of stages performed has not been shown to be influenced by mms surgeon experience level (table 1).5,6 this study aimed to expand on the previously examined influence of surgeon experience level on the number of stages performed during mms by prospectively investigating mohs fellows in-training compared to attending mohs surgeons. the lower experience level of fellows was hypothesized to result in a higher mean number of stages required during mms as compared to the higher experience level and hypothesized lower mean number of stages for attendinglevel surgeons. if accurate, this would demonstrate a higher efficiency for more experienced surgeons in extirpating tumors compared to less experienced surgeons – arguing against previous findings of no significant difference in mean number of stages for different experience levels. data was prospectively collected over a 24month time period from a private and academic clinic. one attending surgeon maintaining active membership with the american college of mohs surgery (acms) and two fellows of an accreditation council for graduate medical education (acgme)accredited mms fellowship formed the data pool. the database collected the experience level cohort, numbers of stages required, diagnosis, and surgical site for 2,140 cases. for the primary objective, surgeons were divided into two cohorts (attending or fellow) based on experience level during each mms procedure. for the secondary objective, diagnoses were confirmed with pathology reporting and intraoperative microscopic examination. in an effort to provide cohesive statistical validity with previous studies evaluating the impact of experience level in mms outcomes, only basal cell carcinomas (bccs) and squamous cell carcinomas (sccs) were included in data analysis as they represent the majority of tumors encountered in mms practice.6 bccs were categorized as superficial, aggressive (infiltrative, micronodular, morpheaform), and non-aggressive (nodular, mixed superficial and nodular). similarly, sccs were categorized as superficial (in situ/bowen’s), aggressive (spindled/moderately-poorly differentiated), and non-aggressive (welldifferentiated/keratoacanthoma-type). if two diagnoses existed within the same tumor, categorization was based on the more aggressive diagnosis. surgical sites were subclassified into high (h), medium (m), and low (l) risk areas according to the 2012 appropriate use criteria (auc) for mms.7 descriptive statistics on the number of stages of each experience level cohort were analyzed using a computer software program (r version 4.0.3 statistical software [2020]; the r foundation, vienna, austria). independent samples t-tests were conducted to compare the mean number of stages between the two experience level cohorts for overall number of stages, number of stages by specific diagnosis, and number of stages by surgical site (defined methods skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 498 table 1. previous literature on the impact of experience level on mohs outcomes reference definitions of experience level cohorts mean number of stages * key findings steinman et al.4 • in-residency only mms training • post-residency courses only • post-residency courses & observational preceptorship 1.66 mean number of stages for non-fellowship trained surgeons compared favorably to previously published reports. alhaddad et al.5 • early (less than five years in practice) • mid (five-to-ten years in practice) • advanced (greater than ten years in practice) 1.88 no significant difference was observed between years in practice and number of stages per case. alam et al.6 • early(less than five years in practice) • mid-career (greater than five years in practice) 1.93 (early) 1.70 (mid) mohs surgeons removed tumors with similar mean numbers of stages regardless of experience level * mean number of stages overall for all variants of bcc and scc. above). statistical significance was defined as p <0.05 the mean number of stages for all mms outcomes regardless of experience level cohort was 1.90, with 99.0% of tumors being removed in four or fewer stages. this data is comparable to previously published data examining experience level influence on mms outcomes (table 1).5,6 independent samples t-tests for mean stages between experience level cohorts for all types of skin cancer is revealed in figure 1. the fellow cohort reported a lower mean number of stages as compared to the attending cohort (1.8 vs. 1.94, respectively; p=0.005). when the difference in mean number of stages between experience level cohorts was stratified by skin cancer diagnoses (table 2), the fellow cohort demonstrated a lower mean number of stages for nonsuperficial, non-aggressive bcc in figure 1. mean number of stages by experience level cohorts for all types of skin cancer results skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 499 comparison to the attending cohort (1.88 vs. 1.65, respectively; p<0.001). no significant differences existed between cohorts in the other specific skin cancer diagnoses. analysis of surgical site separated into areas h, m, and l revealed no difference in the mean number of stages for the two experience level cohorts. within areas h, m, and l, the fellow cohort had a lower mean number of stages, but this failed to reach statistical significance compared to the attending cohort (p=0.088, p=0.067, p=0.762, respectively). previous comparison of attending mms surgeons failed to detect differences in the mean number of stages for early-, mid-, and late-career surgeons (table 1).5,6 early(less than five years in practice) and mid-career (greater than five years in practice) mohs surgeons removed tumors with similar mean numbers of stages.6 further differentiation into early(less than five years in practice), mid(five-to-ten years in practice), and advanced (greater than ten years in practice), showed no significant relationship between years in practice and mean number of stages.5 this study is a novel examination of the influence of in-training experience level on mms stage count. the lower mean number of stages for the less experienced fellow cohort argues against the authors’ hypothesis that the in-training cohort would have a higher mean number of stages. two factors may have influenced these results. the higher mean number of stages for the attending cohort may reflect the increased complexity of cases performed by the attending cohort compared to the fellow cohort. at the training sites in this study, the attending cohort was more likely to be the primary surgeon for the most complex cases (aggressive histology, larger tumor size, challenging anatomical presentations) to promote the best mms outcomes which may create discordance between cohorts. separately, the authors felt the less experienced fellow cohort may take larger initial margins compared to the maximal tissue sparing, smaller margin efforts of the attending cohort. this may result in the fellow cohort incidentally extirpating the tumor in a smaller number of stages (contributing to a lower mean number of stages when compared to the attending cohort) with the trade-off of less normal tissue preservation. when outcomes were broken down by specific skin cancer diagnosis, a lower mean number of stages existed for the fellow cohort when compared to the attending cohort for all types of skin cancer individually, but reached significance only for non-aggressive, nonsuperficial bcc diagnoses. the authors believe non-aggressive, non-superficial bcc diagnoses reached significance because of the high sample size amongst both cohorts within this diagnosis. therefore, nonaggressive, non-superficial bcc reflected the data pool most accurately. superficial and aggressive variants of bcc and scc were secondarily hypothesized to contribute to a higher number of stages for the fellow cohort compared to the attending cohort because of the potential for larger subclinical margins complicating removal. similar to the reasoning behind the overall lower mean number of stages for the fellow cohort, the inverse demonstration of a lower mean number of stages for the fellow cohort when treating superficial and aggressive variants of bcc and scc was felt to also result from larger initial margins and inadvertent tumor clearance (despite possible larger subclinical margins). discussion skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 500 in the 2012 determination of auc for mms, numerous factors were incorporated to table 2. independent samples t-test results for number of stages between training groups by specific skin cancer diagnosis diagnosis attending fellow pvalue abcc n = 376 n = 147 2.36 (1.27) 2.23 (1.14) 0.245 ascc n = 49 n = 22 2.29 (1.51) 2 (1.2) 0.397 bcc n = 729 n = 262 1.88 (1.01) 1.65 (0.76) < 0.001 sbcc n = 30 n = 14 1.9 (1.06) 1.79 (0.8) 0.695 scc n = 317 n = 95 1.5 (0.67) 1.46 (0.62) 0.602 sscc n = 42 n = 18 1.9 (0.88) 1.5 (0.71) 0.067 abcc (aggressive basal cell carcinoma infiltrative, micronodular, morpheaform), ascc (aggressive squamous cell carcinoma spindled/moderately to poorly differentiated), bcc (non-aggressive basal cell carcinoma), sbcc (superficial basal cell carcinoma), scc (nonaggressive squamous cell carcinoma welldifferentiated/keratoacanthoma-type), sscc (superficial squamous cell carcinoma in situ/bowen’s) provide uniform appropriate use recommendations, including body locations grouped based on risk: areas h (high), m (medium), and l (low).7 areas of minimal tissue laxity and high cosmetic sensitivity (i.e. areas h and m) may require a greater number of stages because of the attempt to preserve normal tissue with smaller intraoperative margin choice.6 the authors hypothesized this may translate to a higher mean number of stages for the less experienced fellow cohort compared to the attending cohort. in analysis of the data, while not statistically significant, the fellow cohort demonstrated a lower mean number of stages when compared to the attending cohort for all three areas. previously discussed factors (case distribution, larger initial margin choice) influencing the lower mean number of stages overall for the less experienced fellow cohort may have also contributed to the unexpected results for mean number of stages when separated by anatomical location. the possibility of attentive supervision from the attending mohs surgeon during fellowperformed high-risk cases in areas with high technical and aesthetic concerns impacting this result cannot be ruled out. sampling bias was a limitation of this study. attending and fellow surgeons were analyzed from a single practice and fellowship program, rendering this sample an incomplete representation of all mms clinics and mms fellowships. while the acgme accreditation system unifies fellowship training requirements, considerable variation exists between fellowships in terms of teaching methods for surgical care. additionally, because this study was restricted to one geographical region (midwestern united states) it does not reflect the patient population that may be encountered outside of this study. numerous mms clinics and fellowship programs exist in various parts of the united states, altering the patient population (age, severity of malignancy, overall health state, skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 501 socioeconomic status) and tumor burden that fellows or attendings will encounter at outside programs not assessed in this study.6 therefore, the results of this study may not reflect all in-training mms experiences and outcomes. it is important to recognize the fellows were under training and supervised by the same attending. because of this exposure, fellows may follow a similar technical approach as the attending. as such, training bias is another limitation of this study. this implies these results may not be generalizable to all fellows performing mms, as fellows at other programs are instructed by different attendings who may have different technical approaches and views of training. no uniform recommendations for number of stages in mms exists. benefits and drawbacks exist for both higher and lower stage counts. improved retention of normal tissue, structure, and function may result from higher stage counts; however, an increased operative time and resource utilization may be seen. in contrast, a smaller number of stages portends to reduced operative times and resource utilization but may cause increased loss of normal tissue.6 the authors’ hypothesis of the less experienced fellow cohort demonstrating a higher mean number of stages was disproven as the fellow cohort had a lower mean number of stages compared to the attending cohort. however, this finding does support prior studies, which have failed to find a higher mean number of stages associated with lower experience levels (table 1). overall, the attending cohort had 0.14 more stages on average compared to fellow cohort, which was unlikely to make a significant impact on clinical outcomes. the authors believe an obvious experience gap exists between attending surgeons as compared to in-training fellows. the perceived experience gap was not portrayed in analysis of mean number of stages during mms. factors such as unequal complex case distribution and larger initial margin choice/inadvertent tumor clearance may influence demonstration of this experience gap in regard to mean number of stages. therefore, mean number of stages may not be the best objective measure of experience level. alternatively, when utilizing stage count to evaluate the differences between experience levels of mms surgeons, a higher number of stages may reflect an advanced, tissue-sparing skill level. further studies are warranted to examine the impact of intraining surgeons on mms outcomes. conflict of interest disclosures: none funding: none acknowledgements: the authors appreciate the statistical analysis from caleb scheidel corresponding author: michael visconti, do 5333 mcauley drive, suite r-2111 ann arbor, michigan 48106-0995 phone: 734-712-5563 fax: 734-712-8777 email: michvisconti@gmail.com references: 1. demer am, vance kk, cheraghi n, reich hc, et al. benefit of mohs micrographic surgery over wide local excision for melanoma of the head and neck: a rational approach to treatment. dermatol surg. 2019;45:381-389. 2. asgari mm, bertenthal d, sen s, sahay a, et al. patient satisfaction after treatment of nonmelanoma skin cancer. dermatol surg. 2009;35:1041-1049. 3. chung vq, bernardo l, jiang sb. presurgical curettage appropriately reduces the number of mohs stages by better delineating the subclinical extensions of tumor margins. dermatol surg. 2005;31:1094-1099. conclusion mailto:michvisconti@gmail.com skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 502 4. steinman hk, clever h, dixon a. the characteristics of mohs surgery performed by dermatologists who learned the procedure during residency training or through postgraduate courses and observational preceptorships. proc (bayl univ med cent). 2016;29:119-123. 5. alhaddad m, zade j, nabatian a, kriegel d, et al. association between surgeon-specific features and number of stages, flaps, and grafts in mohs micrographic surgery: a retrospective observational study of 59 early-, mid-, and advanced-career mohs surgeons. dermatol surg. 2017;43:1358-1362. 6. alam m, berg d, bhatia a, et al. association between number of stages in mohs micrographic surgery and surgeon-, patient-, and tumor-specific features: a cross-sectional study of practice patterns of 20 earlyand mid-career mohs surgeons. dermatol surg. 2010;36:1915-1920. 7. ad hoc task force, connolly sm, baker dr, et al. aad/acms/asdsa/asms 2012 appropriate use criteria for mohs micrographic surgery: a report of the american academy of dermatology, american college of mohs surgery, american society for dermatologic surgery association, and the american society for mohs surgery. j am acad dermatol. 2012;67:531-550. references 1. rogers hw et al. jama dermatol. 2015;151:1081–1086. 2. kauvar an et al. dermatol surg. 2015;41:1214–1240. 3. karia ps et al. j am acad dermatol. 2013;68:957–966. 4. burova e et al. mol cancer ther. 2017;16:861–870. 5. migden mr et al. n engl j med. 2018;379:341–351. 6. regeneron. libtayo® (cemiplimab-rwlc) prescribing information. available at https://www.regeneron.com/sites/default/files/ libtayo_fpi.pdf, accessed november 9, 2018. 7. eisenhauer ea et al. eur j cancer. 2009;45:228–247. 8. migden mr et al. poster presentation at eadv 2018 (abstract #2551). acknowledgments we thank the patients, their families, and all investigators involved in this study. the study was funded by regeneron pharmaceuticals, inc., and sanofi. medical writing support and typesetting was provided by emmanuel ogunnowo, phd of prime, knutsford, uk, funded by regeneron pharmaceuticals, inc., and sanofi. copies of this poster obtained through qr (quick response) and/or text key codes are for personal use only and may not be reproduced without written permission of the authors. for any questions regarding this poster presentation, please contact towonik@emory.edu disclosures taofeek k. owonikoko: fees for a consulting or advisory role for novartis, celgene, lilly, sandoz, abbvie, eisai, g1 therapeutics, takeda, seattle genetics, bristol-myers squibb, medimmune. kyriakos p. papadopoulos, marta gil-martin, victor moreno, howard safran, raid aljumaily: none declared. april k. salama: fees for consulting or advisory and speakers’ bureau roles for bristol-myers. emiliano calvo: research funding from boehringer ingelheim, roche/genentech, bms, novartis, psioxus, nanobiotix, janssen, abbvie, pharmamar, puma, sanofi, lilly, pfizer, merck, nektar, amcure, amgen, astrazeneca, principia, bayer, cytomx, h3, incyte, kura, loxo, macrogenics, menarini, merck, serono, merus, millenium, rigontec, tahio, and tesaro; and honoraria or consultation fees from novartis, nanobiotix, janssen-cilag, psioxus therapeutics, seattle genetics, pierre fabre, boehringer ingelheim, cerulean pharma, eusa, abbvie, and celgene; and speaker’s bureau fees from novartis. antonio gonzález-martín: consulting, advisory, speakers’ bureau and travel accommodation expenses from astrazeneca, tesaro, roche and pharmamar. daruka mahadevan: speakers’ bureau and travel, accommodation expenses from abbvie. jiaxin niu: consulting or advisory role fees from genentech, biodesix, paradigm, ignyta, astrazeneca and teueda. kosalai kal mohan, jingjin li, elizabeth stankevich, melissa mathias, israel lowy, matthew g. fury: employees and shareholders of regeneron pharmaceuticals, inc. hani m. babiker: honoraria from bayer and sirtex; and consulting or advisory fees from celgene, and endocyte. poster presented at the 2019 winter clinical dermatology conference, january 18–23, koloa, hawaii (encore of esmo 2018 poster presentation). conclusions • in this analysis of longer follow-up data from cscc expansion cohorts of the phase 1 study, cemiplimab continued to show substantial antitumor activity and a durable response with a safety profile comparable with other anti-pd-1 agents; there were no new safety concerns compared with previous analyses. • primary analysis of the metastatic cscc cohort and prespecified interim analysis of the locally advanced cscc cohort from the phase 2 study (nct02760498) provides further evidence of substantial antitumor activity and durable response with cemiplimab treatment in advanced cscc.5,8 background • cutaneous squamous cell carcinoma (cscc) is the second most common skin cancer after basal cell carcinoma.1 • although cscc has a surgical cure rate of >95%, an estimated 3,932–8,791 patients died from cscc in 2012 in the united states (us).2,3 • cemiplimab (regn2810) is a high-affinity, highly potent human monoclonal antibody directed against programmed death-1 (pd-1).4,5 • cemiplimab is the only food and drug administration (fda)-approved treatment for patients with metastatic or locally advanced cscc who are not candidates for curative surgery or curative radiation in the us.6 • in the primary analysis (data cut-off october 2, 2017), by independent central review, of phase 1 cscc expansion cohorts, cemiplimab demonstrated encouraging efficacy results with acceptable safety profile in patients with advanced cscc.5 • here, we report longer follow-up data, per investigator assessment, from the cscc expansion cohorts of the phase 1 study (nct02383212). objectives • the co-primary objectives of the cscc expansion cohorts were to: characterize the safety and tolerability of cemiplimab 3 mg/kg every two weeks (q2w) evaluate the efficacy of cemiplimab 3 mg/kg q2w by measuring overall response rate (orr). methods • adult patients with metastatic cscc or locally and/or regionally advanced cscc who were not candidates for surgery were enrolled (figure 1). • acceptable reasons for surgery to be deemed inappropriate for patients with locally/regionally advanced cscc were: recurrence of cscc after two or more surgical procedures and an expectation that curative resection would be unlikely, and/or; substantial morbidity or deformity anticipated from surgery. • key inclusion criteria included eastern cooperative oncology group (ecog) performance status of 0 or 1, adequate organ function, and at least one lesion measurable by response evaluation criteria in solid tumors (recist) version 1.1.7 • patients were excluded if they had any ongoing or recent (within 5 years) autoimmune disease requiring systemic immunosuppression; active brain metastases; or invasive malignancy within 5 years. phase 1 study of cemiplimab, a human monoclonal anti-pd-1 antibody, in patients with unresectable locally advanced or metastatic cutaneous squamous cell carcinoma (cscc): longer follow-up efficacy and safety data taofeek k. owonikoko,1 kyriakos p. papadopoulos,2 melissa l. johnson,3 marta gil-martin,4 victor moreno,5 april k. salama,6 emiliano calvo,7 nelson s. yee,8 howard safran,9 raid aljumaily,10 daruka mahadevan,11 jiaxin niu,12 kosalai kal mohan,13 jingjin li,14 elizabeth stankevich,14 melissa mathias,13 israel lowy,13 matthew g. fury,13 hani m. babiker15 1department of hematology and medical oncology, winship cancer institute, emory university, atlanta, ga, usa; 2start, san antonio, tx, usa; 3sarah cannon research institute, nashville, tn, usa; 4institut català d’oncologia-idibell, l’hospitalet de llobregat, barcelona, spain; 5start madrid fjd, hospital fundación jiménez díaz, madrid, spain; 6duke university, durham, nc, usa; 7start madrid, centro integral oncológico clara campal, madrid, spain; 8hematology/oncology division and penn state cancer institute, hershey, pa, usa; 9brown university, providence, ri, usa; 10oklahoma university medical center, oklahoma city, ok, usa; 11the university of arizona cancer center, tucson, az, usa. formerly of the university of tennessee health science center and west cancer center, memphis, tn, usa; 12department of medical oncology, banner md anderson cancer center, gilbert, az, usa; 13regeneron pharmaceuticals, inc., tarrytown, ny, usa; 14regeneron pharmaceuticals, inc., basking ridge, nj, usa; 15the university of arizona cancer center, tuscon, az, usa. table 2. summary of teaes, regardless of attribution, in the combined cscc expansion cohorts teaes n=26 n (%) any grade grade ≥3† any 26 (100.0) 12 (46.2) serious 7 (26.9) 6 (23.1) led to discontinuation 2 (7.7) 1 (3.8) with an outcome of death‡ 1 (3.8) 1 (3.8) occurred in at least four patients fatigue 7 (26.9) 0 decreased appetite 4 (15.4) 0 diarrhea 4 (15.4) 0 hypercalcemia 4 (15.4) 2 (7.7) hypophosphatemia 4 (15.4) 0 nausea 4 (15.4) 0 urinary tract infection 4 (15.4) 1 (3.8) †the only teaes of grade ≥3 that occurred in more than one patient were hypercalcemia and skin infection (each 7.7%). ‡the fatal teae occurred in an 81-year-old man with baseline congestive heart failure and renal insufficiency who later had a teae of urinary tract infection and became anuric. the fatal renal failure was considered unrelated to study treatment. table 1. patient demographics and baseline characteristics metastatic cscc (n=10) locally/ regionally advanced cscc (n=16) total (n=26) median age (range), year 71 (55–85) 73 (56–88) 73 (55–88) ≥65 years old, n (%) 7 (70.0) 14 (87.5) 21 (80.8) male, n (%) 8 (80.0) 13 (81.3) 21 (80.8) ecog performance status score, n (%) 0 4 (40.0) 6 (37.5) 10 (38.5) 1 6 (60.0) 10 (62.5) 16 (61.5) primary cscc site, n (%) head/neck† 5 (50.0) 13 (81.3) 18 (69.2) extremity‡ 3 (30.0) 2 (12.5) 5 (19.2) trunk 1 (10.0) 1 (6.3) 2 (7.7) penis 1 (10.0) 0 1 (3.8) prior systemic therapy for cscc, n (%) 9 (90.0) 6 (37.5) 15 (57.7) prior radiotherapy for cscc, n (%) 6 (60.0) 14 (87.5) 20 (76.9) †includes ear and temple. ‡includes arms/hands and leg/feet. be st p er ce nt ag e ch an ge in ta rg et le si on fr om b as el in e complete response/partial response metastatic cscc locally/regionally advanced cscc progressive disease stable disease 100 80 60 40 20 0 –20 –40 –60 –80 –100 † † figure 2. clinical activity of tumor response to cemiplimab per investigator assessment plot shows the best percentage change in the sum of target lesion diameters from baseline for 22 patients from both cscc expansion cohorts who underwent radiologic evaluation per investigator assessment. lesion measurements after progression were excluded. the horizontal dashed lines indicate criteria for partial response (≥30% decrease in the sum of target lesion diameters) and progressive disease (≥20% increase in the target lesion diameters), respectively. two patients (with cross symbols under bar) had tumor lesion reduction of >30% from baseline; however, best overall response was stable disease as the tumor lesion reduction had not been confirmed. the following four patients do not appear in the figure (but are included in the orr analysis [table 3], per intention-to-treat): one patient with locally advanced cscc who had missing target lesion measurements and three patients (one with metastatic, and two with locally advanced, cscc) with no evaluable post-treatment tumor assessment. stable disease progressive disease unable to evaluate ongoing study partial response complete response metastatic cscc locally/regionally advanced cscc months pa tie nt s w ith re sp on se 0 2 4 6 8 10 12 14 16 18 20 22 plot shows time to response and duration of response in the 13 patients with complete or partial response at the time of data cut-off. each horizontal bar represents one patient. • at the time of data cut-off (january 20, 2018), 12 patients (46.2%) had completed the planned treatment and 14 (53.8%) had discontinued treatment, mainly due to disease progression (n=7). • the median number of administered doses of cemiplimab was 16 (range: 2–44) and the median duration of exposure was 36.0 weeks (range: 4.0–86.7). at the time of data cut-off, two patients had entered the retreatment phase. one of these patients had an extended retreatment phase with an overall 86.7 weeks of continued cemiplimab exposure (beyond the planned 48-week treatment duration) as it was considered, by the investigator, to be in the best interest of the patient. • the median duration of follow-up at the time of data cut-off was 11.9 months (range: 1.1–18.2). treatment-emergent adverse events (teaes) • teaes of any grade, regardless of attribution, were reported in all patients (table 2). • investigator-assessed treatment-related teaes of any grade occurred in 16 patients (61.5%), with four patients (15.4%) experiencing the following five grade ≥3 treatment-related teaes: adrenal insufficiency, asthenia, increased alanine aminotransferase, increased aspartate aminotransferase, and maculo-papular rash. table 3. tumor response by investigator assessment metastatic cscc (n=10) locally/ regionally advanced cscc (n=16) total (n=26) best overall response, n (%) complete response 0 2 (12.5) 2 (7.7) partial response 6 (60.0) 5 (31.3) 11 (42.3) stable disease 1 (10.0) 4 (25.0) 5 (19.2) progressive disease 2 (20.0) 4 (25.0) 6 (23.1) not evaluable† 1 (10.0) 1 (6.3) 2 (7.7) overall response rate, % (95% ci) 60.0 (26.2–87.8) 43.8 (19.8–70.1) 50.0 (29.9–70.1) durable disease control rate, % (95% ci)‡ 60.0 (26.2–87.8) 56.3 (29.9–80.2) 57.7 (36.9–76.6) median observed time to response, months (range)§ 2.7 (1.7–5.5) 1.9 (1.7–7.5) 1.9 (1.7–7.5) observed duration of response of ≥6 months, n (%)§ 4 (66.7) 5 (71.4) 9 (69.2) †include missing and unknown tumor response. ‡defined as the proportion of patients without progressive disease for at least 105 days. §data shown are for patients with confirmed complete or partial response. • the most common investigator-assessed treatment-related teaes of any grade were fatigue (26.9%), arthralgia, diarrhea, hypothyroidism, muscle weakness, and maculo-papular rash (each 7.7%). • two patients discontinued treatment due to treatment-related teaes: an 86-year-old female discontinued treatment after three doses of cemiplimab due to grade 3 rash and grade 2 cough. the patient completed 6 months post-treatment follow-up and had a partial response during the last post-treatment assessment by the investigator a 58-year old male developed grade 2 muscular weakness after five doses of cemiplimab; patient continued treatment for an additional five doses, after disease progression, before treatment was permanently discontinued due to this teae. clinical efficacy • orr by investigator assessment was 50.0% (13/26 patients: 95% confidence interval [ci]: 29.9–70.1; table 3). • durable disease control rate was 57.7% (95% ci: 36.9–76.6). • other selected exclusion criteria were treatment with immunosuppressive doses of steroids (>10 mg prednisone daily or equivalent); systemic antitumor treatment within 4 weeks of initial dose of cemiplimab; history of solid organ transplant; or primary tumors of lip or eyelid. • severity of adverse events was graded according to the national cancer institute common terminology criteria for adverse events (version 4.03). • the data cut-off date was january 20, 2018. results baseline characteristics, disposition, and treatment exposure • twenty-six patients (median age, 73 years; 10 metastatic and 16 locally/regionally advanced cscc) were enrolled. • patient baseline characteristics are summarized in table 1. expansion cohort 7: patients with metastatic cscc expansion cohort 8: patients with locally and/or regionally advanced cscc cemiplimab 3 mg/kg iv q2w, for up to 48 weeks response assessments every 8 weeks (recist 1.17) to determine orr tumor response per investigator assessment figure 1. study design: cscc expansion cohorts iv, intravenous. • rapid, deep, and durable target lesion reductions were observed in most patients who had at least one tumor assessment on treatment (figures 2–4). • median duration of response had not been reached at data cut-off. metastatic cscc locally/regionally advanced cscc months 100 80 60 40 20 0 –20 –40 –60 –80 –100 p er ce nt ag e ch an ge in ta rg et le si on fr om b as el in e 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 plot shows the percent change in target lesion diameters from baseline over time. patients shown in this figure are the same as those in figure 2. the horizontal dashed lines indicate criteria for partial response (≥30% decrease in the sum of target lesion diameters) and progressive disease (≥20% increase in the target lesion diameters). figure 3. change in target lesion over time figure 4. time to and duration of response in responding patients eric l. simpson, md, mcr,1 robert bissonnette, md, frcpc,2 michael e. kuligowski, md, phd, mba,3 may e. venturanza, md,3 kang sun, phd,3 jonathan i. silverberg, md, phd, mph4 introduction ● atopic dermatitis (ad) is a highly pruritic inflammatory skin disease that often involves the head and/or neck (hn)1,2 ● there is a need for well-tolerated treatments that can be used long term on body regions that are prone to irritation/burning and to side effects from topical steroid use, such as the face3 ● in two phase 3 randomized studies of identical design (truead1 [nct03745638] and true-ad2 [nct03745651]), ruxolitinib cream, a topical selective inhibitor of janus kinase (jak) 1/jak2, demonstrated anti-inflammatory activity with antipruritic action vs vehicle and was well tolerated in patients with ad4 objective ● to describe the effect of ruxolitinib cream in adolescent and adult patients with ad with hn involvement using pooled data from two phase 3 trials methods study design and patients ● eligible patients were aged ≥12 years with ad for ≥2 years and had an investigator’s global assessment (iga) score of 2 or 3 and 3%–20% affected body surface area (excluding scalp) ● key exclusion criteria were unstable course of ad, other types of eczema, immunocompromised status, use of ad systemic therapies during the washout period and during the study, use of ad topical therapies (except bland emollients) during the washout period and during the study, and any serious illness or medical condition that could interfere with study conduct, interpretation of data, or patients’ well-being ● true-ad1 and true-ad2 had identical study designs (figure 1) – in both studies, patients were randomized (2:2:1) to 1 of 2 ruxolitinib cream strength regimens (0.75% twice daily [bid] or 1.5% bid) or vehicle cream bid for 8 weeks of double-blind continuous treatment – patients on ruxolitinib cream subsequently continued treatment for 44 weeks; patients initially randomized to vehicle were rerandomized 1:1 (blinded) to either ruxolitinib cream regimen figure 1. study design • treat as needed for 44 weeks • stop treatment 3 days after lesion clearance • rescue treatment not permitted • continuous treatment for 8 weeks • rescue treatment not permitted vehicle-controlled period long-term safety period patients initially randomized to rux remain on their regimen patients on vehicle rerandomized 1:1 to 0.75% rux bid or 1.5% rux bid patients randomized 2:2:1 rux† visits every 4 weeks week 52day 1 week 8 recurrence of lesions clearance of lesions 1.5% rux bid (n=~240 in each study) 0.75% rux bid (n=~240 in each study) vehicle bid (n=~120 in each study) ad, atopic dermatitis; bid, twice daily; bsa, body surface area; rux, ruxolitinib cream. † patients self-evaluated recurrence of lesions between study visits and treated lesions with active ad (≤20% bsa). if lesions cleared between study visits, patients stopped treatment 3 days after lesion disappearance. if new lesions were extensive or appeared in new areas, patients contacted the investigator to determine if an unscheduled additional visit was needed. assessments ● pooled efficacy at week 8 was assessed by achievement of the following endpoints in patients with hn involvement at baseline and the overall population: – iga-treatment success (iga-ts; iga of 0/1 and ≥2-grade improvement from baseline) – ≥50%, ≥75%, and ≥90% improvement in eczema area and severity index vs baseline (easi-50, easi-75, and easi-90 [overall and hn region]) – ≥4-point improvement in itch numerical rating scale score vs baseline (nrs4) 1oregon health & science university, portland, or, usa; 2innovaderm research, montreal, qc, canada; 3incyte corporation, wilmington, de, usa; 4george washington university, washington dc, usa presented at the fall clinical dermatology conference las vegas, nv • october 21–24, 2021 ● percentage change from baseline in easi score (overall and hn region) was also assessed ● safety and application site tolerability were also assessed statistical analyses ● all analyses were conducted using the pooled data from both studies ● easi percentage change from baseline was analyzed by mixedeffect model with repeated measures with statistical significance determined at weeks 2, 4, and 8 ● all other efficacy endpoints were analyzed by logistic regression with statistical significance determined at week 8 ● the efficacy population consisted of 1208 patients (vehicle, n=244; 0.75% ruxolitinib cream, n=483; 1.5% ruxolitinib cream, n=481) results patients ● of 1249 randomized patients, 696 (55.7%) had hn involvement at baseline ● distribution of baseline demographics and clinical characteristics was similar across treatment groups (table 1) table 1. patient demographics and baseline clinical characteristics characteristic vehicle (n=250) 0.75% rux (n=500) 1.5% rux (n=499) total (n=1249) age, median (range), y 34.0 (12–82) 33.0 (12–85) 31.0 (12–85) 32.0 (12–85) female, n (%) 159 (63.6) 304 (60.8) 308 (61.7) 771 (61.7) race, n (%) white 170 (68.0) 345 (69.0) 355 (71.1) 870 (69.7) black 61 (24.4) 118 (23.6) 113 (22.6) 292 (23.4) asian 10 (4.0) 16 (3.2) 20 (4.0) 46 (3.7) other 9 (3.6) 21 (4.2) 11 (2.2) 41 (3.3) region, n (%) north america 172 (68.8) 342 (68.4) 341 (68.3) 855 (68.5) europe 78 (31.2) 158 (31.6) 158 (31.7) 394 (31.5) bsa, mean (sd), % 9.6 (5.5) 10.0 (5.3) 9.6 (5.3) 9.8 (5.4) easi, mean (sd) 7.8 (4.8) 8.1 (4.9) 7.8 (4.8) 8.0 (4.8) easi hn score* 1.2 (0.9) 1.2 (1.0) 1.1 (0.8) na iga, n (%) 2 64 (25.6) 125 (25.0) 123 (24.6) 312 (25.0) 3 186 (74.4) 375 (75.0) 376 (75.4) 937 (75.0) itch nrs score, mean (sd) 5.1 (2.4) 5.2 (2.4) 5.1 (2.5) 5.1 (2.4) ≥4, n (%) 159 (63.6) 324 (64.8) 315 (63.1) 798 (63.9) duration of disease, median (range), y 16.5 (0.8–79.1) 15.1 (0.1–68.8) 16.1 (0–69.2) 15.8 (0–79.1) facial involvement, n (%)† 93 (37.2) 195 (39.0) 197 (39.5) 485 (38.8) number of flares in last 12 mo, mean (sd)† 7.3 (25.7) 5.2 (6.7) 6.0 (17.6) 5.9 (16.5) bsa, body surface area; easi, eczema area and severity index; hn, head and/or neck; iga, investigator’s global assessment; na, not available; nrs, numerical rating scale; rux, ruxolitinib cream. * patients with hn involvement in the efficacy-evaluable population (vehicle, n=136; 0.75% rux, n=265; 1.5% rux, n=262). † patient reported. efficacy ● iga-ts (figure 2) and itch nrs4 (figure 3) were achieved by significantly more patients who applied ruxolitinib cream compared with vehicle at week 8 (p<0.0001) – response rates were numerically greater among patients with hn involvement vs the overall population ● significantly greater improvements from baseline in total easi and hn region scores were observed with ruxolitinib cream vs vehicle at week 8 (p<0.0001; figure 4) ● significantly more patients who received ruxolitinib cream vs vehicle achieved easi-50 (figure 5; p<0.0001), easi-75 (figure 6; p<0.0001), and easi-90 (figure 7; p<0.0001) at week 8 – response rates were numerically greater among patients with hn involvement vs the overall population figure 2. iga-ts in the hn and overall populations vehicle (n=136) 0.75% rux (n=265) 1.5% rux (n=262) vehicle (n=244) 0.75% rux (n=483) 1.5% rux (n=481) 0 10 20 30 40 50 60 70 80 90 100 week 2 week 4 week 8 week 2 week 4 week 8 2.2 4.4 8.1 3.7 6.1 11.5 26.0 47.2 54.3 19.9 39.1 44.7 29.4 48.9 56.5 26.2 45.1 52.6 **** **** **** **** hn involvement overall population pr op or tio n (s e) o f p at ie nt s ac hi ev in g ig ats , % † hn, head and/or neck; iga-ts, investigator’s global assessment-treatment success; rux, ruxolitinib cream. **** p<0.0001 vs vehicle. † defined as patients achieving an iga score of 0 or 1 with an improvement of ≥2 points from baseline. patients with missing post-baseline values were imputed as nonresponders at weeks 2, 4, and 8. figure 3. itch nrs4 in the hn and overall populations vehicle (n=90) 0.75% rux (n=181) 1.5% rux (n=170) vehicle (n=158) 0.75% rux (n=313) 1.5% rux (n=307) 0 10 20 30 40 50 60 70 80 90 100 week 2 week 4 week 8 week 2 week 4 week 8 hn involvement overall population 5.6 10.0 13.3 5.1 12.0 15.8 29.3 40.3 48.1 26.8 38.3 41.5 38.2 57.6 59.4 32.9 48.5 51.5**** **** **** **** pr op or tio n (s e) o f p at ie nt s ac hi ev in g itc h nr s4 , % † hn, head and/or neck; nrs4, ≥4-point improvement in itch numerical rating scale score from baseline; rux, ruxolitinib cream. **** p<0.0001 vs vehicle. † patients in the analysis had an itch nrs score ≥4 at baseline. patients with missing post-baseline values were imputed as nonresponders at weeks 2, 4, and 8. effects of ruxolitinib cream in patients with atopic dermatitis with head and/or neck involvement safety ● application site reactions were less frequent in patients who applied ruxolitinib cream regardless of hn involvement compared with vehicle (table 2) ● among patients who applied ruxolitinib cream, application site pain (ie, stinging/burning) was reported in 5/555 patients (0.9%) with hn involvement and 7/999 (0.7%) in the overall population (vs 8/141 [5.7%] and 12/250 [4.8%] among patients who applied vehicle, respectively) – no application site reactions were serious table 2. application site reactions in the hn and overall populations ae, n (%) hn population overall population vehicle (n=141) rux (combined) (n=555) vehicle (n=250) rux (combined) (n=999) application site reactions* 13 (9.2) 14 (2.5) 18 (7.2) 19 (1.9) pain 8 (5.7) 5 (0.9) 12 (4.8) 7 (0.7) pruritus 5 (3.5) 4 (0.7) 7 (2.8) 6 (0.6) irritation 2 (1.4) 2 (0.4) 2 (0.8) 2 (0.2) erythema 2 (1.4) 0 2 (0.8) 1 (0.1) dryness 0 1 (0.2) 0 1 (0.1) folliculitis 0 1 (0.2) 0 2 (0.2) exfoliation 0 1 (0.2) 0 1 (0.1) papules 0 1 (0.2) 0 1 (0.1) swelling 0 0 1 (0.4) 0 ae, adverse event; rux, ruxolitinib cream. * patients may report more than 1 type of application site reaction. conclusions ● in patients with ad with hn involvement, ruxolitinib cream showed superior efficacy compared with vehicle ● ruxolitinib cream was well tolerated (ie, low rates of stinging/burning) in patients with hn involvement with a safety profile comparable to the overall population disclosures els is an investigator for abbvie, eli lilly, galderma, kyowa hakko kirin, leo pharma, merck, pfizer, and regeneron; and is a consultant with honorarium for abbvie, eli lilly, forte bio, galderma, incyte corporation, leo pharma, menlo therapeutics, novartis, pfizer, regeneron, sanofi genzyme, and valeant. rb is a consultant with honoraria for abbvie, arena, bluefin, boehringer ingelheim, cara therapeutics, kyowa kirin, pfizer, and respivant; an investigator with grants/research funding for abbvie, arcutis, arena, asana biosciences, bellus, boehringer ingelheim, cara therapeutics, eli lilly, incyte corporation, pfizer, rapt, and sanofi genzyme; an advisor with honoraria for arena, eli lilly, galderma, incyte corporation, leo pharma, pfizer, and rapt; and an employee and shareholder of innovaderm research. mek was an employee and shareholder of incyte corporation at the time of development of the original presentation. mev and ks are employees and shareholders of incyte corporation. jis received honoraria for advisory board, speaker, and consultant services from abbvie, asana, bluefin, boehringer ingelheim, celgene, dermavant, dermira, eli lilly, galderma, glaxosmithkline, glenmark, incyte corporation, kiniksa, leo pharma, menlo therapeutics, novartis, pfizer, realm, regeneron, and sanofi; and research grants for investigator services from galderma and glaxosmithkline. acknowledgments the authors thank the patients, investigators, and investigational sites whose participation made the study possible. support for this study was provided by incyte corporation (wilmington, de, usa). writing assistance was provided by tania iqbal, phd, an employee of icon (north wales, pa, usa), and was funded by incyte corporation. references 1. langan sm, et al. lancet. 2020;396(10247):345-360. 2. silverberg ji, et al. j eur acad dermatol venereol. 2019;33(7):1341-1348. 3. eichenfield lf, et al. j am acad dermatol. 2014;71(1):116-132. 4. papp k, et al. j am acad dermatol. 2021;85(4):863-872. figure 4. easi percentage change from baseline in the (a) hn and overall populations and (b) based on hn region score vehicle 0.75% rux 1.5% rux m ea n (9 5% c i) pe rc en ta ge ch an ge f ro m b as el in e in ea si s co re , % m ea n (9 5% c i) pe rc en ta ge ch an ge f ro m b as el in e in ea si h n re gi on s co re , % week 2 week 4 week 8 week 2 week 4 week 8 –13.1 –55.6 –58.8 –19.7 **** **** **** –72.7 –74.2 –76.5 –79.3**** **** **** **** –34.5 –14.8 –48.9 –53.2 –22.3 –66.9 **** –68.9 –34.7 –73.4 –76.0**** **** **** **** number of patients vehicle 0.75% rux 1.5% rux 124 252 254 115 253 252 110 246 245 226 461 461 211 457 461 202 430 450 0 hn involvement a) b) overall population –20 –40 –60 –80 –100 20 0 –20 –40 –60 –80 –100 bl 2 4 8 number of patients vehicle 0.75% rux 1.5% rux 124 252 253 115 253 251 110 246 245 –13.4 –22.4 –45.0 –55.8 –71.3 –78.7 –59.3 –70.4 –70.0 **** **** **** **** **** **** vehicle 0.75% rux 1.5% rux bl, baseline; easi, eczema area and severity index; hn, head and/or neck; rux, ruxolitinib cream. **** p<0.0001 vs vehicle. figure 5. easi-50 in the (a) hn and overall populations and (b) based on hn region score vehicle (n=136) 0.75% rux (n=265) 1.5% rux (n=262) vehicle (n=244) 0.75% rux (n=483) 1.5% rux (n=481) a) b) vehicle (n=136) 0.75% rux (n=256) 1.5% rux (n=262) 0 10 20 30 40 50 60 70 80 90 100 pr op or tio n (s e) o f p at ie nt s ac hi ev in g ea si -5 0, % † 0 20 40 60 80 100 pr op or tio n (s e) o f p at ie nt s ac hi ev in g e as i-5 0 hn r eg io n, % bl 2 4 8 time, wk week 2 week 4 week 8 week 2 week 4 week 8 hn involvement overall population 49.3 76.6 84.4 **** **** 26.5 36.8 66.0 79.266.8 80.2 16.2 26.5 36.0 57.0 76.2 63.7 79.4 79.2 **** 81.7 **** 18.0 28.3 38.9 49.5 69.2 72.5 58.2 73.8 78.8 **** **** bl, baseline; easi-50, ≥50% improvement in eczema area and severity index score from baseline; hn, head and/or neck; rux, ruxolitinib cream. **** p<0.0001 vs vehicle. † patients with missing post-baseline values were imputed as nonresponders at weeks 2, 4, and 8. figure 6. easi-75 in the (a) hn and overall populations and (b) based on hn region score vehicle (n=136) 0.75% rux (n=265) 1.5% rux (n=262) vehicle (n=244) 0.75% rux (n=483) 1.5% rux (n=481) a) b) vehicle (n=136) 0.75% rux (n=256) 1.5% rux (n=262) 4.4 11.0 18.4 31.3 55.5 62.6 34.4 57.6 67.2**** **** week 2 week 4 week 8 week 2 week 4 week 8 hn involvement overall population 4.9 12.3 19.7 28.0 47.0 53.8 33.9 54.7 62.0 **** **** 0 10 20 30 40 50 60 70 80 90 100 pr op or tio n (s e) o f p at ie nt s ac hi ev in g ea si -7 5, % † 31.6 63.8 74.0 **** **** 11.0 21.3 45.3 65.3 45.0 66.0 0 20 40 60 80 100 pr op or tio n (s e) o f p at ie nt s ac hi ev in g ea si -7 5 hn r eg io n, % bl 2 4 8 time, wk bl, baseline; easi-75, ≥75% improvement in eczema area and severity index score from baseline; hn, head and/or neck; rux, ruxolitinib cream. **** p<0.0001 vs vehicle. † patients with missing post-baseline values were imputed as nonresponders at weeks 2, 4, and 8. figure 7. easi-90 in the (a) hn and overall populations and (b) based on hn region score vehicle (n=136) 0.75% rux (n=265) 1.5% rux (n=262) vehicle (n=244) 0.75% rux (n=483) 1.5% rux (n=481) a) b) vehicle (n=136) 0.75% rux (n=256) 1.5% rux (n=262) 0 10 20 30 40 50 60 70 80 90 100 pr op or tio n (s e) o f p at ie nt s ac hi ev in g ea si -9 0, % † 0 20 40 60 80 100 pr op or tio n (s e) o f p at ie nt s ac hi ev in g ea si -9 0 hn r eg io n, % 9.6 15.4 25.0 34.0 49.4 52.8 32.4 51.5 63.0**** **** bl 2 4 8 time, wk 0.7 2.2 5.9 15.1 34.0 42.6 19.5 36.3 45.4**** **** 1.6 3.3 7.0 11.8 28.2 36.6 17.9 34.5 43.9 **** **** week 2 week 4 week 8 week 2 week 4 week 8 hn involvement overall population bl, baseline; easi-90, ≥90% improvement in eczema area and severity index score from baseline; hn, head and/or neck; rux, ruxolitinib cream. **** p<0.0001 vs vehicle. † patients with missing post-baseline values were imputed as nonresponders at weeks 2, 4, and 8. to download a copy of thisposter, scan code. skin may 2019 volume 3 issue 3 copyright 2018 the national society for cutaneous medicine 190 in-depth reviews treatment of brachioradial pruritus: a systematic review katerina yale, md,1 margit juhasz, md, msc,2 natasha atanaskova mesinkovska, md, phd2 1 university of california, irvine, department of medicine, irvine, ca 2 university of california, irvine, department of dermatology, irvine, ca brachioradial pruritus (brp) is an uncommon disorder first described in the late 1960s as “pruritus of the upper extremities.”1 while originally thought to be caused by excessive sunlight exposure, later reports demonstrate a neuropathic component.2,3 due to uncertain pathology, a wide variety of treatment options have been trialed. over 50 years later, there is still no clear therapeutic modality for brp. brp occurs with higher prevalence in women (72% to 87.4%) and patients with fair skin tones (52% to 86%). patients present over a wide age range from 12 to 84 years, however the fifth decade is the average age at diagnosis.4–7 brp is described as pruritus, tingling and/or stinging on unilateral or importance: brachioradial pruritus (brp) is a poorly understood disease and can severely impact quality of life. however, there is currently no clear treatment. objective: to identify effective behavioral, topical, oral, and invasive treatment options for brp, and to discuss the quality of the data currently found in the literature. evidence review: the pubmed and cinahl databases were systematically reviewed for articles from 1968 to the present containing search terms “brachioradial or solar or forearm and pruritus or itching.” results were narrowed to articles written in english, focusing specifically on brp, and that stated precise treatment modalities. evidence quality was determined using the oxford centre for evidence-based medicine criteria based on the study type. findings: thirty-six articles discussing treatments for brp are included in this review with a total 399 patients. six studies (n=68) report on the efficacy of capsaicin cream, eight studies (n=26) on oral gabapentin 300 mg daily to six times daily and four studies (n=98) on sun protection. the remaining articles comprise of low-quality, small-scale studies on further oral medications, physical therapy, minimally-invasive procedures, and surgery. conclusions and relevance: low-quality evidence supports the use of sun protection, topical capsaicin, or oral gabapentin as effective therapeutic modalities for brp. clinicians should be aware of possible underlying cervical spine pathology and include thorough imaging as part of brp work-up. further high-quality studies on brp treatments would help elucidate clear management for this disorder. introduction abstract skin may 2019 volume 3 issue 3 copyright 2018 the national society for cutaneous medicine 191 bilateral dorsolateral aspect(s) of the upper extremity(ies) without overt cutaneous findings, and may spread to the upper torso.5,8 disease etiology includes local neurocutaneous damage from ultraviolet (uv) radiation and/or cervical spinal nerve injury.2,3,8 retrospective studies demonstrate 34.1% to 77% of patients have worsening symptoms in summer, 48.6% to 59% note exacerbation after sun exposure, and 30% to 80.5% have cervical spine abnormalities.3–7 while brp appears to be a benign disease, it causes significant impairment in patient quality of life (qol).6,7,9 typical pruritus treatments, such as corticosteroids or antihistamines, are unsuccessful in treating brp. current brp treatments focus on preventing sun exposure or addressing potential neuropathic aspects, however, many lack efficacy. in this systematic review, we evaluate the literature surrounding brp, and aim to answer the question: what is the most effective treatment for brp? a systematic literature search was performed using pubmed and cinahl databases with search terms “brachioradial and pruritus or itching,” “solar and pruritus or itching,” and “forearm and pruritus or itching” in august 2018. all clinical trials, observational studies, case series, case reports, and commentaries from 1968 to the present were included. exclusion criteria consisted of articles that were in a language other than english, articles that did not state a clear, effective treatment modality for each case of brp, or articles that did not distinguish an effective treatment for brp from other forms of neuropathic itch (notalgia paresthetica, postherpetic neuralgia, etc.). the evidence quality level for each study was determined using the oxford centre for evidence-based medicine criteria. in total, 169 individual articles were screened. after exclusion criteria, 36 articles were reviewed consisting of one randomized clinical trial (rct), five prospective cohort studies, eight retrospective studies, seven case series, fourteen case reports, and one commentary. after removing duplicate data (pinto et al./waccholz et al. and pereira et al./stienke et al.), 399 patients with brp were included.4,9–11 given that most data on brp treatment comes from case series and reports, the overall quality of the evidence reviewed is low (table 1-4). pharmacological treatments topical medications topical therapies, specifically capsaicin, are typically first-line treatment for brp. six studies (one rct, one prospective cohort study, one retrospective study, two case series, and one case report), address the effectiveness of capsaicin 0.025% to 0.1% cream for brp (n=68).5,12–16 in the rct, thirteen patients with bilateral brp were treated with capsaicin cream 0.025% to one arm and placebo cream to the other five times daily for one week, then three times daily for four weeks. capsaicin was not significantly more effective than placebo, with both demonstrating over 60% pruritus resolution.12 a non-blinded trial of capsaicin cream 0.025% to one arm four times daily compared to no treatment of the second arm (n=15) showed a 76% reduction in pruritus by capsaicin after three weeks.13 while many case reports note improvement in symptoms with topical capsaicin, they describe an unpleasant burning sensation and a methods results skin may 2019 volume 3 issue 3 copyright 2018 the national society for cutaneous medicine 192 recurrence of symptoms after treatment is discontinued.13–16 capsaicin 8% patch is another treatment option for brp. two prospective cohort studies and one case series (n=30), have reported on its effective use in brp after one hour of application.9,11,17 one study described an 85% reduction in itch as soon as three weeks post-treatment and lasting three months, while two others reported a statistically significant decrease in pruritus six months after treatment .17,9,11 while 27% of patients require another patch applied at three months, and 13.7% another at six months, all patients noted a significant improvement in qol.9,11 side effects include intense burning, which can be mitigated by pre-treatment with topical lidocaine.17 other topicals studied for brp include amitriptyline 1%/ketamine 0.5% cream, topical steroids, doxepin cream and local anesthetics. one retrospective study and one case report described topical amitriptyline 1%/ketamine 0.5% for brp (n=12). complete resolution of pruritus was noted in 33.3% of patients with daily use, while 25% noted only improvement.5,18 historically, topical steroids such as hydrocortisone, triamcinolone, and fluocinonide have been tried for brp without much success.1,5,6,15,16,19,20 the use of topical steroids, doxepin cream, and local anesthetics has been described in one retrospective study. of patients treated with topical steroids (n=22), 18% noted complete resolution of symptoms and 27% reported improvement. in the same study nine patients were treated with doxepin cream with 22% describing complete resolution and another 22% noting some improvement. as for topical anesthetics (n=42), no patients reported complete resolution of symptoms with pramocaine cream or lidocaine patches, and only 12.5% noted some improvement with pramocaine.5 systemic medications oral medications used for brp include anticonvulsants, antidepressants, antipsychotics, neurokinin (nk)-1 receptor inhibitors, non-steroidal anti-inflammatory drugs (nsaids), and antihistamines. the most commonly cited oral medication for brp treatment is gabapentin with eight articles (three retrospective studies, one case series, four case reports; n=26) reporting on gabapentin efficacy.4,5,10,19,21–24 effective doses range from 300 mg once daily to six times daily.19,21–23 however, side effects such as sedation and gastrointestinal upset may limit the upper limit of dosing in some patients.22 retrospective studies note complete resolution of brp in 20% to 42% of patients, while partial symptomatic control was achieved in 20% to 28.5%.5,10 other anticonvulsants used for brp include pregabalin, lamotrigine, and carbamazepine.5,25,26 one prospective study and one case report (n=4) noted improvement in pruritus with pregabalin. seventy-five percent of patients attained complete resolution with 75 mg pregabalin twice daily, while 25% required 225 mg daily.26,27 in one case, lamotrigine 200 mg daily produced symptomatic resolution.25 similarly, in another case, carbamazepine demonstrated symptomatic improvement, however no dose was reported.5 antidepressants, such as amitriptyline, doxepin and fluoxetine, and antipsychotics, such as risperidone, pimozide and chlorpromazine, have occasionally been used to treat brp.4,5,10 two retrospective studies (n=53) noted these medications have a similar effect as gabapentin, with a majority skin may 2019 volume 3 issue 3 copyright 2018 the national society for cutaneous medicine 193 of patients noting either “excellent” or “good” reduction in pruritus. unfortunately, no doses were reported.4,10 antihistamines and nsaids are rarely prescribed for brp. while antihistamines are classically thought to be anti-pruritic, they are typically ineffective in brp. 1,6,15,16 only 10% of patients prescribed antihistamines note some improvement in pruritus (n=10).5 in cases of cervical-pathology related brp, successful treatment has been noted with nsaids, with and without a combination of physical therapy (n=5).20,28,29 one patient noted improved pruritus in as little as three days after daily 100 mg oral ketoprofen.29 a novel medication being used in brp is the nk-1 receptor antagonist, aprepitant. in a case of recalcitrant brp, oral aprepitant 80 mg daily gave symptomatic improvement. however, symptoms returned after treatment cessation and were not as well-controlled after a second course of medication.30 procedural treatments invasive treatments have been tried for refractory brp or those with clear cervical spine pathology.28,31–34 one case noted dramatic improvement with botulinum toxin (100 iu total) injected at 1.5 cm intervals over the symptomatic area every five to six months.31 similarly, epidural steroid injections in four patients gave 75% of patients lasting relief from pruritus after one injection, while 25% required multiple injections to gain long-term relief. 33,35 a case of brp associated with spinal cord injury was treated with stellate ganglion catheter placement and ropivacaine infusion, achieving partial pruritus relief. side effects including upper extremity temperature change, piloerection, and conjunctival injection were noted.34 surgical treatment of brp is reserved for cases with correctable cervical pathology. for example, one case of brp was secondary to a cervical rib. of note, surgery was not pursued until additional neurological symptoms, including paresthesia and restricted range of motion, were noted in the brp-affected arm.28 non-pharmacological treatments behavioral intervention initially brp was only described in patients with excessive sun exposure, and treatments were directed at sun avoidance and protection.1 four articles (one retrospective study, one case series, one case report, and one commentary; n=98), report on the effectiveness of long-sleeve clothing for brp.1,7,36,37 high sun protection factor (spf) sunscreens were effective in two studies for relieving pruritus (n=58).7,37 sun protection relieves pruritus in as little as four weeks, and can provide continuing relief if behavioral modification is sustained.7,37 physical therapy in the 1980s, the role of nerve damage in brp was first reported.20 three retrospective studies and one case series (n=22), report cervical physical therapy or cervical traction and/or manipulation as effective treatment for brp.5,20,28,38 in one case series, all patients (n=5) with cervical degenerative changes and brp had improvement in pruritus with either physical therapy, cervical traction and/or manipulation.20 another study demonstrated that cervical spine manipulation resolved pruritus from two days up to permanently in 100% of patients with a history of neck problems (n=6), and 50% of patients with no neck problems (n=8).38 a further case series (n=3) noted a reduced skin may 2019 volume 3 issue 3 copyright 2018 the national society for cutaneous medicine 194 number of patients (33%) with pruritus resolution after cervical physical therapy when the cervical pathology was unknown.5 cutaneous field stimulation or acupuncture one prospective study (n=9) using cutaneous field stimulation, daily electrical stimulation of pruritic skin patches, on brp patients demonstrated effectiveness at reducing pruritus intensity in all patients. however, symptoms returned for 88.9% of patients 3 to 12 months after treatment.39 similarly, one retrospective study (n=10) described the use of acupuncture in brp, and found all patients achieved relief of pruritus with deep cervical paravertebral muscle stimulation. again, 40% demonstrated symptomatic relapse 1 to 12 months later.40 while a wide variety of therapeutic modalities have been tried for brp, many have not been studied in large-scale rcts. there is no strong consensus on the most effective treatment – for instance, in one retrospective study, 19 different treatment modalities had been tried on brp patients over ten years, with 54% of patients being prescribed more than one therapy. only 12% of patients reported complete resolution of pruritus with treatment.5 this shot-gun approach to brp treatment may be related to the disorder’s ambiguous etiology. brp pathogenesis is most likely multifactorial, involving uv-induced neurocutaneous damage and cervical radiculopathy.3,41 in a prospective cohort study, patients with brp have significantly reduced levels of calcitonin gene-related protein (a sensory nerve marker) and total number of intraepithelial nerve fibers in symptomatic skin. these findings are similar to findings after serial phototherapy, which is consistent with the hypothesis that prolonged uv damage plays a role in the development of brp.41 however, another prospective study reported a significant relationship between cervical stenosis and nerve compression, as seen by mri, correlating to dermatomal pruritus in brp.3 although many cases of brp do not have a clear cause, cervical pathology is noted frequently enough to recommend that patients follow with a neurologist and cervical imaging is performed. similarly, if cervical pathology is noted, physical therapy or other non-pharmacologic options may be useful with or without the addition of further medications. while evidence supporting the effectiveness of sun protection in brp is low, dermatologic benefits associated with sun avoidance are such that it is worth advising patients to add protection to their treatment regimen. current treatments focus on blockade of nerve sensation at the local or systemic level. unmyelinated c-fibers play a prominent role transmitting epidermal itch sensation through thermosensors, which modulate itch, heat, and pain, as well as the nk-1 receptor which binds substance p.42,43 capsaicin modulates the itch pathway by depleting substance p and regulating thermosensor expression.44 further upstream, modulation of excitatory neurotransmitters with gabapentin can change itch perception through afferent neuron signal transmission and central hypersensitivity.45 of the topical treatments reviewed, capsaicin has the most evidence supporting its use in brp. while the only rct on topical capsaicin cream demonstrated no significant improvement in pruritus versus placebo, discussion skin may 2019 volume 3 issue 3 copyright 2018 the national society for cutaneous medicine 195 difficulty blinding capsaicin’s burning sensation may have limited study quality. it would be beneficial to repeat this study with placebo cream that better mimics capsaicin’s side effects. the capsaicin patch is an appealing alternative, given the need for less frequent application. topical amitriptyline/ketamine cream may also be a promising treatment option, however large-scale studies are needed to determine its true effectiveness and longterm adverse effects. oral gabapentin is the most commonly discussed systemic treatment. gabapentin inhibits calcium ion channels on afferent neurons thus preventing excitatory neurotransmitter release.45 evidence for gabapentin’s use in brp is low given the lack of rcts and prospective studies. while anecdotally, it seems to be an effective medication, high doses are required to provide symptomatic relief. side effects, such as sedation and gastrointestinal upset, may prevent its use by patients.22 pregabalin may be a useful alternative for brp, however there is a paucity of high-quality evidence for its use as well. some antidepressants (amitriptyline, doxepin, fluoxetine) and antipsychotics (risperidone, pimozide) can be equally as effective as gabapentin in treating brp, and may provide an affordable option for patients.10 duloxetine and mirtazapine have been used for the treatment of neuropathic pruritus, however large-scale rcts using antidepressants and/or antipsychotics in brp have not been done.46,47 aprepitant, an nk-1 receptor antagonist originally approved for the prevention of chemotherapy-induced nausea and vomiting, has also been reported to be effective in chronic pruritides.30,48 anecdotal evidence demonstrates effect in brp, however more studies are needed to support this medication.30 invasive treatment is appropriate when there is clear cervical pathology for brp. epidural steroid injections improve c-fiber functionality and provide long-term symptomatic control in brp.35 surgical treatment is appropriate with underlying correctable cervical spine pathology.8 even then, surgical treatment is considered as a last option and is not typically pursued unless additional neurological symptoms, such as weakness, paresthesia or pain, are present.28,49 it is important to carefully consider risks and benefits of invasive treatment options given the lack of highquality evidence, and thoroughly counsel patients before attempting these modalities. limitations to this review include the current lack of rcts and high-quality prospective studies investigating therapies for brp. although many medications show promise, their use is supported by small studies, case series and case reports. while ideally more studies should be performed to better assess efficacy and adverse events of existing treatment modalities, new therapies are currently being developed that may benefit brp patients. modulators of the protease pathway, such as nafamostat mesillate and tetracyclines, target protease-activated receptor (par)-2 and modulate the cowhage itch pathway. cannabinoids target vanilloids, impacting itch perception. furthermore, future therapies may target centrally and effect dorsal root ganglion molecules.50 brp is an uncommon disorder that can have a large impact on patient qol and morbidity. currently there are no clear, effective treatment choices. it is important that conclusion skin may 2019 volume 3 issue 3 copyright 2018 the national society for cutaneous medicine 196 clinicians are aware of possible underlying cervical spine etiology, and disease follow-up should include thorough imaging work-up for cervical spine abnormalities. review of the literature demonstrates low-quality evidence supporting sun protection, physical therapy, topical capsaicin cream (0.025% to 0.1%) and patch (8%), as well as oral gabapentin (300 mg daily to six times daily) as effective therapeutic modalities. many other medications such as topical steroids, antihistamines and anesthetics, as well as oral antihistamines, antidepressants, antipsychotics and nsaids have anecdotally been reported to improve symptoms of brp. novel treatments such as nk-1 receptors are being investigated for use in brp. conflict of interest disclosures: none. funding: none. corresponding author: katerina yale, md university of california, irvine department of dermatology irvine, ca yalekl@uci.edu references: 1. waisman m. solar pruritus of the elbows (brachioradial summer pruritus). arch dermatol. 1968;98(5):481-485. doi:10.1001/archderm.1968.0161017004 1006. 2. walcyk pj, elpern dj. brachioradial pruritus: a tropical dermopathy. br j dermatol. 1986;115:177-180. doi:10.1111/j.1365-2133.1986.tb05714.x. 3. marziniak m, phan nq, raap u, et al. brachioradial pruritus as a result of cervical spine pathology: the results of a magnetic resonance tomography study. j am acad dermatol. 2011;65:756-762. doi:10.1016/j.jaad.2010.07.036. 4. pinto acvd, masuda py, wachholz pa, carlos a, martelli c. clinical, epidemiological and therapeutic profile of patients with brachioradial pruritus in a reference service in dermatology. an bras dermatol. 2016;91(4):549-551. 5. mirzoyev sa, davis mdp. brachioradial pruritus: mayo clinic experience over the past decade. br j dermatol. 2013;169:1007-1015. doi:10.1111/bjd.12483. 6. masuda py, martelli acc, wachholz pa, akumatsu ht, martins algp, silva nm. brachioradialer pruritus deskriptive analyse einer brasilianischen fallserie. jddg j ger soc dermatology. 2013;11(6):530-536. doi:10.1111/ddg.12009. 7. veien nk, laurberg g. brachioradial pruritus: a follow-up of 76 patients. acta derm venereol. 2011;91(2):183-185. doi:10.2340/00015555-1006. 8. robbins ba, schmieder gj. brachioradial pruritus. treasure island (fl): statpearls publishing; 2017. 9. steinke s, gutknecht m, zeidler c, et al. cost-effectiveness of an 8% capsaicin patch in the treatment of brachioradial pruritus and notalgia paraesthetica, two forms of neuropathic pruritus. acta derm venereol. 2017;97(1):71-76. doi:10.2340/00015555-2472. 10. wachholz pa, masuda py, pinto acvd, martelli acc. impact of drug therapy on brachioradial pruritus. an bras dermatol. 2017;92(2):281-282. doi:10.1590/abd1806-4841.20175321. 11. pereira mp, lüling h, dieckhöfer a, steinke s, zeidler c, ständer s. brachioradial pruritus and notalgia paraesthetica: a comparative observational study of clinical presentation and morphological pathologies. acta derm venereol. 2018;98:82-88. doi:10.2340/000155552789. 12. wallengren j. brachioradial pruritus: a recurrent solar dermopathy. j am acad dermatol. 1998;39:803-806. doi:10.1016/s0190-9622(99)80074-7. mailto:nmesinko@uci.edu skin may 2019 volume 3 issue 3 copyright 2018 the national society for cutaneous medicine 197 13. knight te, hayashi t. solar (brachioradial) pruritus response to capsaicin cream. int j dermatol. 1994;33(3):206-209. 14. barry r, rogers s. brachioradial pruritus an enigmatic entity. clin exp dermatol. 2004;29:637-638. doi:10.1111/j.13652230.2004.01642.x. 15. goodless dr, eaglstein wh. brachioradial pruritus: treatment with topical capsaicin. j am acad dermatol. 1993;29(5):783-784. doi:10.1016/s0190-9622(08)81703-3. 16. lane je, mckenzie jt, spiegel j. brachioradial pruritus: a case report and review of the literature. cutis. 2008;81:3740. 17. zeidler c, lüling h, dieckhöfer a, et al. capsaicin 8% cutaneous patch: a promising treatment for brachioradial pruritus? br j dermatol. 2015;172:16691671. doi:10.1111/bjd.13501. 18. poterucha tj, murphy sl, davis mdp, et al. topical amitriptyline-ketamine for the treatment of brachioradial pruritus. jama dermatology. 2013;149(2):148-150. doi:10.1001/2013.jamadermatol.646. 19. carvalho s, sanches m, alves r, selores m. brachioradial pruritus in a patient with cervical disc herniation and parsonageturner syndrome. an bras dermatol. 2015;90(3):401-402. doi:10.1590/abd1806-4841.20153059. 20. heyl t. brachioradial pruritus. arch dermatol. 1983;119:115-116. 21. winhoven sm, coulson ih, bottomley ww. brachioradial pruritus: response to treatment with gabapentin. br j dermatol. 2004;150(4):786-787. doi:10.1111/j.0007-0963.2004.05889.x. 22. kanitakis j. brachioradial pruritus: report of a new case responding to gabapentin. eur j dermatology. 2006;16(3):311-312. 23. bueller h, bernhard jd, dubroff l. gabapentin treatment for brachioradial pruritus. j eur acad dermatology venereol. 1999;13:227-230. doi:10.1093/jahist/jav675. 24. yilmaz s, ceyhan am, baysal akkaya v. brachioradial pruritus successfully treated with gabapentin. j dermatol. 2010;37:662665. doi:10.1111/j.13468138.2010.00830.x. 25. crevits l. brachioradial pruritus-a peculiar neuropathic disorder. clin neurol neurosurg. 2006;108:803-805. doi:10.1016/j.clineuro.2005.12.001. 26. atış g, bilir kaya b. pregabalin treatment of three cases with brachioradial pruritus. dermatol ther. 2017;30:1-3. doi:10.1111/dth.12459. 27. vestita m, cerbone l, calista d. brachioradial pruritus in a 47-year-old woman treated with pregabalin. g ital di dermatologia e venerelogia. 2016;151(6):727-728. 28. rongioletti f. pruritus as presenting sign of cervical rib. lancet. 1992;339:55. 29. abbott l. neuropathic pruritus. australas j dermatol. 1998;39:198-200. doi:10.1093/jahist/jav675. 30. ally ms, gamba cs, peng dh, tang jy. the use of aprepitant in brachioradial pruritus. jama dermatology. 2013;149(5):627-628. doi:10.1001/jamadermatol.2013.170. 31. kavanagh gm, tidman mj. botulinum a toxin and brachioradial pruritus. br j dermatol. 2012;166:1147. doi:10.1111/j.1365-2133.2011.10749.x. 32. goodkin r, wingard e, bernhard jd. brachioradial pruritus: cervical spine disease and neurogenic/neuropathic pruritus. j am acad dermatol. 2003;48:521-524. doi:10.1067/mjd.2003.203. 33. weinberg bd, amans m, deviren s, berger t, shah v. brachioradial pruritus treated with computed tomography-guided cervical nerve root block: a case series. jaad case reports. 2018;4(7):640-644. doi:10.1016/j.jdcr.2018.03.025. 34. crane da, jaffee km, anjana k. intractable pruritus after traumatic spinal cord injury. j spinal cord med. 2009;32(4):436439. 35. deridder d, hans g, pals p, menovsky t. a c-fiber-mediated neuropathic brachioradial pruritus. j neurosurg. 2010;113:118-121. skin may 2019 volume 3 issue 3 copyright 2018 the national society for cutaneous medicine 198 doi:http://dx.doi.org/10.3171/2009.9.jns 09620. 36. orton di, wakelin sh, george sa. brachioradial photopruritus a rare chronic photodermatosis in europe. br j dermatol. 1996;135:486-487. doi:10.1111/j.1365-2133.1996.tb01523.x. 37. armstrong dkb, bingham ea. brachioradial pruritus an uncommon photodermatosis presenting in a temperate climate. dermatology. 1997;195:414-415. 38. tait cp, grigg e, quirk cj. brachioradial pruritus and cervical spine manipulation. australas j dermatol. 1998;39:168-170. 39. wallengren j, sundler f. cutaneous field stimulation in the treatment of severe itch. arch dermatol. 2001;137:1232-1325. doi:10.1001/archderm.137.10.1323. 40. stellon a. neurogenic pruritus: an unrecognised problem? a retrospective case series of treatment by acupuncture. acupunct med. 2002;20(4):186-190. doi:10.1136/aim.20.4.186. 41. wallengren j, sundler f. brachioradial pruritus is associated with a reduction in cutaneous innervation that normalizes during the symptom-free remissions. j am acad dermatol. 2005;52:142-145. doi:10.1016/j.jaad.2004.09.030. 42. pereira mp, lüling h, dieckhöfer a, et al. application of an 8% capsaicin patch normalizes epidermal trpv1 expression but not the decreased intraepidermal nerve fibre density in patients with brachioradial pruritus. j eur acad dermatology venereol. 2018:1-7. doi:10.1111/jdv.14857. 43. cowen a, yosipovitch g. pharmacology of itch. vol 226.; 2015. doi:10.1007/978-3662-44605-8_7. 44. gooding smd, canter ph, coelho hf, boddy k, ernst e. systematic review of topical capsaicin in the treatment of pruritus. int j dermatol. 2010;49:858-865. doi:10.1111/j.1365-4632.2010.04537.x. 45. anand s. gabapentin for pruritus in palliative care. am j hosp palliat med. 2013;30(2):192-196. doi:10.1177/1049909112445464. 46. cohen ad, masalha r, medvedovsky e, vardy da. brachioradial pruritus: a symptom of neuropathy. j am acad dermatol. 2003;48(6):825-828. doi:10.1067/mjd.2003.494. 47. yosipovitch g, samuel ls. neuropathic and psychogenic itch. dermatol ther. 2008;21:32-41. doi:10.1111/j.15298019.2008.00167.x. 48. he a, alhariri jm, sweren rj, kwatra mm, kwatra sg. aprepitant for the treatment of chronic refractory pruritus. biomed res int. 2017;2017:1-6. doi:10.1155/2017/4790810. 49. skelton f, frontera j. brachioradial pruritus as a harbinger of syrinx in chronic spinal cord injury: a case report. pm r. 2017;9:311-313. doi:10.1016/j.pmrj.2016.08.005. 50. dhand a, aminoff mj. the neurology of itch. brain. 2014;137:313-322. doi:10.1093/brain/awt158. skin may 2019 volume 3 issue 3 copyright 2018 the national society for cutaneous medicine 199 table 1. summary of articles describing topical treatment options for brp. author (year) study type (quality) no. of patients patient characteristics treatment study results pereira et al.11 (2018) prospective cohort study (2) 29 65.5% f mean age 61.5 y/o 86.2% with cervical spine abnormalities on mri, decreased intraepidermal nerve fiber density 8% capsaicin patch applied for 1 hr (1 hr pretreatment with topical lidocaine) 8 patients needed reapplication at 3 mo and 4 patients at 6 mo 6 mo f/u pruritus significantly decreased at 3 wk, 3 mo, and 6 mo significant improvement in quality of life steinke et al.9 (2017) prospective cohort study (2) 25 75% f mean age 61.3 y/o mean disease duration 16.9 mo 8% capsaicin patch applied to the pruritic area for 1 hr repeat patch application at 3 mo and 6 mo if symptomatic 6 mo f/u pruritus significantly decreased quality of life significantly improved zeidler et al.17 (2015) case series (4) 5 80% f age range 54-69 y/o c5-c6 dermatomal pruritus reduced intraepidermal nerve fiber density on punch biopsy 8% capsaicin patch for 1 hr (1 hr pretreatment with topical lidocaine) 3 mo f/u 85% reduction in itch after 3 wk and 3 mo poterucha et al.18 (2013) case report (5) 1 41y/o m r arm pruritus, summer exacerbations progressed to year-round c3 and c5 narrowed interspaces on radiography 1% amitriptyline/0.5% ketamine cream applied 2-3 times/d 4 yr f/u complete pruritus relief lane et al.16 (2008) case report (5) 1 46 y/o f l arm pruritus, no seasonal variation, hx of c4-c6 discectomy with topical capsaicin cream (dose n/a, f/u time n/a) moderate pruritus relief skin may 2019 volume 3 issue 3 copyright 2018 the national society for cutaneous medicine 200 osteophytes on mri barry and rogers14 (2004) case series (4) 7 57.1% f with b/l arm pruritus 42.9% exacerbation in sunlight 57.1% with cervical spine disease 0.025% capsaicin cream 4 times/d 8 wk f/u 25 mg/d amitriptyline if no response to capsaicin 57.1% with significant improvement in pruritus after 68 wk with topical capsaicin 28.6% with no relief from capsaicin but relief with amitriptyline wallengren12 (1998) double-blind randomized, controlled trial (1) 13 69.2% f average age 52 y/o 100% with b/l arm pruritus 92.3% with seasonal variation (worse in summer) 0.025% capsaicin cream applied to one arm 5 times/d for 1 wk, then 3 times/d for 4 wk placebo cream applied to the other arm capsaicin cream reduced itch by 63.1 +/ 2% placebo cream reduced itch by 65.5% +/2.9% 84.6% had recurrent of symptoms the following summer knight and hayashi13 (1994) prospective cohort study (2) 15 50% f majority age 30-49 y/o 100% b/l arm pruritus no seasonal variation in symptoms no report of cervical spine abnormalities 0.25% capsaicin cream to one arm 4 times/d for 3 wk other arm left untreated as control 76% noted significant decrease in pruritus after 3 wk 2 patients dropped out due to intolerable burning sensation 6 patients had recurrence of pruritus 1 wk-7 mo later goodless et al.15 (1993) case series (4) 2 patient 1 60 y/o m b/l arm pruritus, chronic sun exposure, hx of rheumatoid arthritis patient 1 0.033% capsaicin cream4-5 times/d for 2 wk 4 mo f/u patient 1 pruritus resolved in 2 wk skin may 2019 volume 3 issue 3 copyright 2018 the national society for cutaneous medicine 201 patient 2 50 y/o f b/l arm pruritus, hx of mva patient 2 0.1% capsaicin cream used 4-5 times/d for 2 wk 4 mo f/u patient 2: pruritus resolved in 2 wk table 2. summary of articles describing systemic treatment options for brp. author (year) study type (quality) number of patients patient characteristics treatment study results atis and kaya26 (2017) prospective cohort study (2) 3 100% f with b/l arm pruritus no seasonal variation no x-ray or mri abnormalities in cervical spine 75 mg pregabalin bid for 1 wk, reduced to 100mg daily for 1 mo 2 mo f/u 66.6% with complete resolution of pruritus 33.3% needed 225mg pregabalin daily to reach complete resolution wachholz et al.10 (2017) retrospective study (3) 49 73.5% f mean age 58 y/o 81.6% caucasian oral amitriptyline, doxepin, gabapentin, risperidone, pimozide, fluoxetine, chlorpromazine, and hydroxyzine prescribed for brp for any period of time between 2011-2014 average 36 mo f/u 38.8% patients reported excellent reduction in pruritus (gabapentin, amitriptyline, doxepin, risperidone, pimozide) best reduction noted with higher intensity pruritus and longer therapy period pinto et al.4 (2016) retrospective study (3) 49 73% f mean age 56.1 y/o 77.6% b/l arm pruritus 59.2% exacerbated with sun exposure 61.2% narrowing of cervical intervertebral spaces oral tricyclic antidepressants (tcas), doxepin, antipsychotics, anticonvulsants, serotonin reuptake inhibitors (ssris) and antihistamines prescribed for any period of time for brp between 2011 and 2014 average 35 mo f/u 59.2% of patients treated with monotherapy 33.3% used tcas, 22.8% doxepin, 18.1% antipsychotics, 10.6% anticonvulsants, 6.1% ssris 79.2% with treatment effectiveness “very good” or “good” skin may 2019 volume 3 issue 3 copyright 2018 the national society for cutaneous medicine 202 vestita et al.27 (2016) case report (5) 1 47 y/o f r arm pruritus, worse in summer r c6-c7 disc herniation and c4-c7 arthrosis 75 mg pregabalin bid for 90 d physiotherapy with cervical traction 10 mo f/u resolution of pruritus in 15 days continued relief at f/u carvalho et al.19 (2015) case report (5) 1 60 y/o f r arm pruritus, no seasonal variation c6-c7 nerve compression 900 mg/d gabapentin indefinitely 3 mo f/u significant control of pruritus ally et al.30 (2013) case report (5) 1 61 y/o f b/l arm pruritus, seasonal exacerbations c4-c6 foraminal stenosis 80 mg/d aprepitant for 7 d, followed by 80 mg/d for 14 d after relapse 48hrs off medication 6 wk f/u significant improvement after 7 d course with relapse 48hrs after d/c some improvement in pruritus after 14 d course, but not well controlled mirzoyev et al.5 (2013) retrospective study (3) 111 72% f mean age 59 y/o 75.7% b/l arm pruritus 45.9% seasonal exacerbations 33% with cervical abnormalities on imaging topical treatments (capsaicin, triamcinolone, pramocaine, doxepin, amitriptyline/ketamine, hydrocortisone, lidocaine, fluocinonide) and oral treatments (gabapentin, pregabalin, carbamazepine, oxymetazoline, cetirizine, hydroxyzine, diphenhydramine, allegra, desloratadine), and physical therapy prescribed for brp for any period of time between 1999-2011 average 18.5 mo f/u 75 patients completed f/u 9 had complete resolution (amitriptylineketamine cream, topical capsaicin, topical doxepin) 13 had improvement (topical capsaicin, triamcinolone, carbamazepine, gabapentin, topical doxepin) yilmaz et al.24 (2010) case report (5) 1 64 y/o m 300 mg/d gabapentin indefinitely markedly reduced pruritus at 4 wks skin may 2019 volume 3 issue 3 copyright 2018 the national society for cutaneous medicine 203 r arm pruritus, no seasonal variation mri with right foraminal stenosis at c4c5 and c6/c7 disc protrusion 1 yr f/u with complete resolution by 4 mo recurrence of pruritus if treatment interrupted crevits25 (2006) case report (5) 1 54 y/o f r arm pruritus followed by l arm pruritus after l shoulder injury mri with midcervical spondylosis 1st course: 200 mg/d lamotrigine for 18 mo 2nd course: 100 mg/d lamotrigine for 8 wks 3 yr f/u complete resolution of r arm pruritus while on lamotrigine and for 6 mo after d/c treatment, at which time a l shoulder injury precipitated l arm pruritus, resolved with 100 mg/d lamotrigine no recurrence after d/c 2nd course kanitakis22 (2006) case report (5) 1 54 y/o m b/l arm pruritus, no seasonal variation or relation to sun exposure x-ray with cervical arthrosis of c5-c7 400 mg gabapentin tid for 2 mo, 600 mg tid for 4 mo, 1200 mg/d to 600 mg/d for 2 mo 8-9 mo f/u some improvement with gabapentin at 400 mg tid significant symptomatic improvement with the addition of topical 8% calamine and essential fatty acid cream side effect at 600 mg tid: sedation and diarrhea recurrence of pruritus after gabapentin d/c winhoven et al.21 (2004) case series (4) 2 patient 1 67 y/o f b/l arm pruritus, no seasonal variation patient 1 300 mg gabapentin tid, then transitioned to 300 mg/d indefinitely f/u time n/a patient 1 significant relief with tid and daily dosing skin may 2019 volume 3 issue 3 copyright 2018 the national society for cutaneous medicine 204 x-ray with moderate degenerative changes from c4 downwards patient 2 51 y/o f b/l arm pruritus x-ray with b/l cervical ribs and degenerative changes at c5c6 patient 2 300mg gabapentin tid indefinitely f/u time n/a patient 2 significant relief bueller et al.23 (1999) case report (5) 1 54 y/o f l arm pruritus, initially worse in summer, then became yearround, exacerbated with sunlight mri with left and central bony ridging at c5-c6 300 mg gabapentin 6 times/d indefinitely 4 mo f/u complete resolution of symptoms abbot29 (1998) case report (5) 1 74 y/o m l arm pruritus x-ray with cervical foraminal narrowing at c2c7 100 mg/d ketoprofen for 3 d f/u time n/a patient noted complete improvement in pruritus sporadic recurrent episodes of pruritus since treatment table 3. summary of articles describing procedural interventions for the treatment of brp. author (year) study type (quality) number of patients patient characteristics treatment study results weinberg et al.33 (2018) case series (4) 3 100% f average 66 y/o b/l arm pruritus 100% with foraminal stenosis on cervical imaging ct-guided epidural injection of 2:1:1 ratio dexamethasone, bupivacaine, and lidocaine repeat injections at 3 mo and 6 mo after initial injection patient 1 complete resolution of symptoms after 1 injection patient 2 near complete resolution after 1 injection and oral skin may 2019 volume 3 issue 3 copyright 2018 the national society for cutaneous medicine 205 patient 1 – 2 mo f/u patient 2 – 3 mo f/u patient 3 – 15 mo f/u pregabalin indefinitely patient 3 complete resolution of pruritus after 3 injections and oral mexiletine indefinitely kavanagh and tidman31 (2012) case report (5) 1 59 y/o f b/l arm pruritus, no report of seasonal variation no cervical abnormalities 10 ul botulinum a toxin (100 iu/3ml saline total) injections at 1.5 cm intervals over symptomatic area every 5-6 mo 2 yr f/u significant relief recurrence 5-6 mo after treatment de ridder et al.35 (2010) case report (5) 1 56 y/o m l arm pruritus mri showing foraminal stenosis at l c4-c5 and b/l c5-c6 fluoroscopicallyguided injection of 80 mg methylprednisolone and 40 mg lidocaine at c6 and c8 midline 6 mo f/u improved pruritus, continued relief crane et al.34 (2009) case report (5) 1 18 y/o f l arm pruritus traumatic spinal cord injury at c6 stellate ganglion block with ropivacaine, then stellate ganglion catheter with ropivacaine infusion 34 mo f/u block with 2 d pruritus relief catheter placement with 4 wk relief and return of pruritus at milder severity rongioletti28 (1992) case series (4) 2 patient 1 22 y/o m year-round l arm pruritus c7 transverse process hypertrophy on xray patient 2 58 y/o f year-round left arm pruritus supernumerary short cervical rib diclofenac (dose n/a) and cervical physical therapy for both patients for 1.5 wk surgical resection of cervical rib in patient 2 after development of cervico-brachialgia, paresthesias, and restricted motion 6 mo after physical therapy 6 mo f/u patient 1 improvement in pruritus, continued relief after therapy patient 2 improvement in pruritus, total resolution of pruritus postsurgery table 4. summary of articles describing behavioral changes for the treatment of brp. skin may 2019 volume 3 issue 3 copyright 2018 the national society for cutaneous medicine 206 author (year) study type (quality) number of patients patient characteristics treatment study results veien and laurberg7 (2011) retrospective study (3) 95 87% f median age 55 y/o 83% b/l arm pruritus 82% seasonal variation 17% year-round symptoms 38.9% cervical foraminal narrowing on imaging sun protection (clothing or spf50+ sunscreen) 3 yr f/u pruritus resolved in 40 of 45 (88.9%) with seasonal symptoms and 4 of 5 (80%) with year-round symptoms armstrong et al.37 (1997) case report (5) 1 47 y/o m b/l arm pruritus, worse in summer, exacerbated by sunlight no cervical spine abnormalities sun avoidance (closeknit clothing and highfactor sunscreen) 4 wk f/u pruritus resolved in 4 wks orton et al.36 (1996) case series (4) 2 patient 1 57 y/o m b/l arm pruritus, no seasonal variation cervical spondylosis patient 2 48 y/o m l arm pruritus, no seasonal variation, history of tanning bed use no cervical abnormalities sun avoidance (long sleeve, close-knit clothing, no tanning bed use) patient 1 – 1 yr f/u patient 2 – 6 mo f/u patient 1 pruritus resolved in 6 wks patient 2 pruritus resolved in 10 wks waisman1 (1968) commentary (5) n/a typically m average age 3050 y/o b/l or l arm pruritus, summer sun protection (long sleeve clothing specifically, no sunscreen) improvement in pruritus skin may 2019 volume 3 issue 3 copyright 2018 the national society for cutaneous medicine 207 recurrence of symptoms, history of chronic sun exposure table 5. summary of articles describing non-pharmacological treatments of brp. author (year) study type (quality) number of patients patient characteristics treatment study results stellon40 (2002) retrospective study (3) 10 62.5% f median age 68 y/o pruritus from dermatomes c3c8 deep intramuscular stimulation to paravertebral muscles correlating to dermatome with symptoms repeated q1-2 wk average 4 treatments, 100% with resolution 4 patients with relapse (1-12 mo later) wallengren and sundler39 (2001) prospective cohort study (2) 9 77.8% f average age 49.9 y/o 77.8% b/l arm pruritus 0.8 ma continuouscurrent electrode plate applied to pruritic area for 20 min/d for 5 wk 12 mo f/u cutaneous field stimulation reduced pruritus by half all but one patient relapsed 3-12 mo after treatment tait et al.38 (1998) retrospective study (3) 14 age range 41-72 y/o 50% b/l arm pruritus 50% seasonal variation 42.9% history of neck problems cervical spine manipulation (head rotation away from the symptomatic side with traction for 1-2 sec before click felt) repeat sessions prn 71.4% with resolution of pruritus (100% of patients with a history of neck problems, 50% of patients with no neck problems), lasting 2 d to permanently heyl20 (1983) retrospective study (3) 14 35.7% f median age 46 y/o 35.7% b/l arm pruritus 30% seasonal variation (worse in summer) 5 patients with cervical imaging (80% with degenerative changes between c4-c7) 3 patients with degenerative changes on cervical imaging and no history of neck treatment given cervical physical therapy or cervical traction/manipulation significant improvement in pruritus noted with cervical physical therapy for 1 patient, cervical traction for 1 patient, and cervical manipulation plus physical therapy for third patient skin december 2018 volume 2 supplemental issue copyright 2018 the national society for cutaneous medicine 107 rising derm stars off-label treatment of prurigo nodularis with dupilumab: a case series study nicholas k. mollanazar, md, mba1, kevin savage, ba1, sylvia hsu, md1 1department of dermatology, lewis katz school of medicine at temple university, philadelphia, pennsylvania introduction: prurigo nodularis (pn) is a chronic, debilitating disease of unknown etiology without any current fda-approved treatments1. no randomized clinical for pn exist currently. each treatment modality that has been described in the literature to date has offered minimal improvement with high risks of serious adverse side effects. in this case series, we present a promising potential new option for the treatment of prurigo nodularis. methods: case series of 3 female patients (age range 37-57 years) diagnosed with prurigo nodularis with history of multiple treatment failures. each patient was treated with the standard fda approved dosing regimen of dupilumab (dupixent, regeneronsanofi), a fully human monoclonal igg antibody that targets the alpha subunit receptor site of il-4, blocking the effects of the il-4 and il-13 signaling pathway2. the standard dosing regimen included 600mg sq injection induction dose followed by 300mg sq injections every two weeks thereafter. to quantify the effectiveness of dupilumab in treating the itch of pn, average patient reported numeric rating scale itch intensity (nrsi) were calculated on a scale of 0-10 before and during therapy with dupilumab. additionally, all patients were monitored for adverse side effects during treatment. results: prior to initiation of therapy, two patients had nrsi scores of 10/10 and one patient had an nrsi of 6/10 giving an average of 8.6/10. during treatment with dupilumab, none of the patients experienced any adverse side effects including itchy or red eyes. after one month of therapy, one patient reported an nrsi of 3/10, while the other two patients reported nrsi of 0/10. at 3 month follow-up, all 3 patients reported nrsi of 0/10. no side effects were reported. discussion: in a recent retrospective study from a tertiary itch center, prurigo nodularis was a common cause of chronic pruritus with the highest reported mean nrsi (8.7 ± 1.7) and the lowest reduction in mean nrsi (-1.9 ± 3) after treatment3. many potential treatments have been described in the literature with unsatisfactory response to treatment and serious adverse side effects1, 4-5. additionally, all of these treatments are currently used off-label for the treatment of pn. the three patients presented experienced an average nsri of 8.6/10, which is in line with previous reports3. the average reduction in nrsi in our three skin december 2018 volume 2 supplemental issue copyright 2018 the national society for cutaneous medicine 108 patients (-8.6), however, is much higher than other reported treatment modalities. while this report is limited, with only three subjects presented, the magnitude of the response to dupilumab in our three patients with pn is remarkable. our findings raise the specter of new potential therapy for the treatment of pn, warranting randomized clinical trials. references: references: 1. fostini ac, girolomoni g, tessari g. prurigo nodularis: an update on etiopathogenesis and therapy. j dermatolog treat. 2013;24(6):458-462. doi:10.3109/09546634.2013.814759 2. beck la, thaçi d, hamilton jd, et al. dupilumab treatment in adults with moderate-to-severe atopic dermatitis. n engl j med. 2014;371(2):130-139. doi:10.1056/nejmoa1314768 3. mollanazar nk, sethi m, rodriguez rv, et al. retrospective analysis of data from an itch center: integrating validated tools in the electronic health record. j am acad dermatol. 2018;75(4):842-844. doi:10.1016/j.jaad.2016.05.035 4. dawn ag, yosipovitch g. butorphanol for treatment of intractable pruritus. j am acad dermatol. 2018;54(3):527-531. doi:10.1016/j.jaad.2005.12.010 5. hundley jl, yosipovitch g. mirtazapine for reducing nocturnal itch in patients with chronic pruritus: a pilot study. j am acad dermatol. 2018;50(6):889-891. doi:10.1016/j.jaad.2004.01.045 deucravacitinib improves psoriasis symptoms and signs diary domain scores in patients with moderate to severe plaque psoriasis: results from the phase 3 poetyk pso-1 and poetyk pso-2 studies april w armstrong,1 bruce strober,2 kenneth b gordon,3 joe zhuo,4 brandon becker,4 renata m kisa,4 john throup,4 jonghyeon kim,4 kim papp5 1keck school of medicine, university of southern california, los angeles, ca, usa; 2yale university, new haven, ct, and central connecticut dermatology, cromwell, ct, usa; 3medical college of wisconsin, milwaukee, wi, usa; 4bristol myers squibb, princeton, nj, usa; 5probity medical research, waterloo, on, canada introduction • tyrosine kinase 2 (tyk2) is an intracellular kinase that mediates signaling of key cytokines (interleukin [il]-23, il-12, and type i interferons [ifns]) involved in psoriasis pathogenesis1 • deucravacitinib is a novel, oral, and selective inhibitor that binds to the regulatory domain of tyk2, and thereby via an allosteric mechanism inhibits signaling of il-23, il-12, and type i ifn1 • in the phase 3 poetyk pso-1 and pso-2 trials, deucravacitinib demonstrated superiority compared with placebo and apremilast for multiple endpoints, including clinical and patient-reported outcomes2 — results from the psoriasis symptoms and signs diary (pssd) focusing on patient-reported symptoms were previously described at the 2021 american academy of dermatology annual meeting2 objective • to compare the effect of deucravacitinib vs placebo and vs apremilast on item-level changes over time for patient-reported psoriasis symptoms and signs measured by the pssd, and to further evaluate the contribution of individual subdomains on symptom and sign scores in poetyk pso-1 and pso-2 methods study designs • poetyk pso-1 (nct03624127) and pso-2 (nct03611751) were 52-week, phase 3, double-blind trials that randomized patients with moderate to severe plaque psoriasis (body surface area [bsa] involvement ≥10%, psoriasis area and severity index [pasi] score ≥12, static physician’s global assessment [spga] score ≥3) 2:1:1 to deucravacitinib 6 mg once daily, placebo, or apremilast 30 mg twice daily2 • patients recorded psoriasis symptoms and signs daily (24-h recall) using the pssd — the pssd is a patient-reported instrument that assesses the severity of 5 symptoms (burning, itch, pain, skin tightness, stinging) and 6 signs (bleeding, cracking, dryness, redness, scaling, shedding or flaking) on a numerical scale ranging from 0 (absent) to 10 (worst imaginable)3,4 — psoriasis symptom and sign summary scores (0–100) were derived based on average scores for the individual symptom and sign domains results baseline disease characteristics • a total of 666 and 1020 patients were randomized in pso-1 and pso-2, respectively2 • in both trials, pssd total and symptom and sign summary scores were similar across groups at baseline (table 1) table 1. baseline pssd total and summary scores poetyk pso-1 poetyk pso-2 mean pssd score (min, max) placebo (n=166) deucravacitinib (n=332) apremilast (n=168) placebo (n=255) deucravacitinib (n=511) apremilast (n=254) total 53.4 (6.1, 100.0) 53.5 (0.0, 100.0) 57.4 (1.0, 100.0) 52.9 (0.0, 100.0) 55.0 (5.9, 100.0) 54.5 (8.2, 100.0) symptom 51.4 (0.3, 100.0) 51.7 (0.0, 100.0) 56.2 (2.0, 100.0) 50.1 (0.0, 100.0) 52.3 (1.0, 100.0) 51.9 (0.0, 100.0) sign 55.5 (9.4, 100.0) 55.3 (0.0, 100.0) 58.6 (0.0, 100.0) 55.7 (0.0, 100.0) 57.7 (5.7, 100.0) 57.2 (11.7, 100.0) max, maximum; min, minimum; pssd, psoriasis symptoms and signs diary. • pssd symptom and sign domain scores were also similar across groups at baseline (data not shown) pssd scores • deucravacitinib-treated patients experienced significantly greater improvements in mean change from baseline in pssd total scores, symptom summary scores, and sign summary scores compared with those receiving placebo or apremilast at week 16 and week 24 (figure 1) figure 1. mean change from baseline in pssd total scores, symptom summary scores, and sign summary scores at week 16 and week 24 –36.3† –25.0 –35.0† –24.2 –37.6† –25.8 –34.9† –27.0 –33.0† –25.2 –36.9† –28.9 –7.0 –6.3 –7.7 –33.2*† –32.0* † –34.3*† –24.5 –23.7 –25.4 -50 -40 -30 -20 -10 0 pssd total score pssd symptom score pssd sign score m e an c h an ge f ro m b as e li n e week 16 poetyk pso-1 poetyk pso-2 week 24 deucravacitinib 6 mg qdplacebo apremilast 30 mg bid –4.8 –3.2 –6.3 –33.1*† –31.3* † –35.0*† –24.7 –23.0 –26.5 -50 -40 -30 -20 -10 0 pssd total score pssd symptom score pssd sign score m e an c h an ge f ro m b as e li n e poetyk pso-1 -50 -40 -30 -20 -10 0 pssd total score pssd symptom score pssd sign score poetyk pso-2 -50 -40 -30 -20 -10 0 pssd total score pssd symptom score pssd sign score *p<0.0001 vs placebo. †p<0.0001 vs apremilast. modified baseline observation carried forward was used to impute missing data. bid, twice daily; pssd, psoriasis symptoms and signs diary; qd, once daily. • significantly greater improvements from baseline were observed in all individual symptom and sign domain scores at week 16 for patients treated with deucravacitinib compared with placebo or apremilast and were consistent between pso-1 and pso-2 (figure 2) — the greatest improvements in psoriasis symptoms were observed for itch, skin tightness, and pain in both studies — the greatest improvements in psoriasis signs were observed for dryness, scaling, and shedding or flaking figure 2. mean change from baseline in pssd symptom domain scores and pssd sign domain scores at week 16 -5 -4 -3 -2 -1 0 m e an c h an ge f ro m b as e li n e poetyk pso-1 pssd symptom domain scores poetyk pso-2 pssd symptom domain scores deucravacitinib 6 mg qdplacebo apremilast 30 mg bid -5 -4 -3 -2 -1 0 m e an c h an ge f ro m b as e li n e poetyk pso-1 pssd sign domain scores -5 -4 -3 -2 -1 0 poetyk pso-2 pssd sign domain scores -5 -4 -3 -2 -1 0 –0.6 –0.7 –0.6 –0.8 –0.5 –3.1*† –3.6*† –3.1*† –3.4*† –2.8*† –2.3 –2.7 –2.1 –2.7 –2.1 burning itch pain skin tightness stinging –0.3 –0.5 –0.2 –0.5 –0.1 –2.9*† –3.6*† –2.9*† –3.5*† –2.7*† –2.1 –2.7 –2.3 –2.6 –1.8 burning itch pain skin tightness stinging –0.6 –0.6 –0.7 –0.6 –0.6 –0.7 –2.2*† –3.4*† –3.9*† –3.5*† –3.9*† –4.0*† –1.6 –2.6 –2.9 –2.6 –3.0 –3.1 bleeding cracking dryness redness scaling shedding or flaking –0.6 –0.9 –0.8 –0.7 –0.9 –0.8 –2.3*† –3.5*† –3.8*† –3.6*† –3.6*† –3.8*† –1.8 –2.6 –2.9 –2.6 –2.7 –2.7 bleeding cracking dryness redness scaling shedding or flaking *p<0.0001 vs placebo. †p<0.01 vs apremilast. modified baseline observation carried forward was used to impute missing data. bid, twice daily; pssd, psoriasis symptoms and signs diary; qd, once daily. • benefits favoring deucravacitinib increased or were maintained through week 24 and were consistent between pso-1 and pso-2 (figure 3) figure 3. mean change from baseline in pssd symptom domain scores and pssd sign domain scores at week 24 -5 -4 -3 -2 -1 0 m e an c h an ge f ro m b as e li n e poetyk pso-1 pssd symptom domain scores poetyk pso-2 pssd symptom domain scores -5 -4 -3 -2 -1 0 m e an c h an ge f ro m b as e li n e poetyk pso-1 pssd sign domain scores -5 -4 -3 -2 -1 0 poetyk pso-2 pssd sign domain scores -5 -4 -3 -2 -1 0 burning itch pain skin tightness stinging burning itch pain skin tightness stinging bleeding cracking dryness redness scaling shedding or flakingbleeding cracking dryness redness scaling shedding or flaking –3.4† –4.0† –3.3† –3.9† –3.1† –2.3 –2.7 –2.2 –2.6 –2.2 –3.1† –3.9† –3.0† –3.8† –2.8† –2.3 –3.0 –2.5 –2.7 –2.1 –2.4† –3.8† –4.2† –3.9† –4.1† –4.2† –1.8 –2.7 –2.9 –2.6 –2.7 –2.8 –2.3† –3.6† –4.2† –3.8† –4.1† –4.3 –1.8 –2.9 –3.2 –2.9 –3.2 –3.3 deucravacitinib 6 mg qd apremilast 30 mg bid †p<0.01 vs apremilast. modified baseline observation carried forward was used to impute missing data. bid, twice daily; pssd, psoriasis symptoms and signs diary; qd, once daily. conclusions • in this post hoc analysis, deucravacitinib treatment was significantly superior to placebo and apremilast in improving individual patientreported psoriasis symptoms and signs at week 16 in patients with moderate to severe plaque psoriasis — benefits favoring deucravacitinib were maintained at week 24 • the greatest symptom improvement was consistently observed for the itch domain — this may prove particularly meaningful to patients given the prevalence and burden of itch, a symptom that affects the vast majority of patients with psoriasis5 • improvements in the patient-reported psoriasis symptoms and signs burden are consistent with the higher clinical response rates previously reported in deucravacitinib-treated patients in pso-1 and pso-22 references 1. burke jr et al. sci transl med 2019;11:1-16. 2. armstrong a et al. presented at the annual meeting of the american academy of dermatology; april 23-25, 2021. 3. feldman sr et al. j dermatol trans surg 2016;20:19-26. 4. mathias sd et al. j dermatol treat 2016;27:322-327. 5. komiya e et al. int j mol sci 2020;21:8406. acknowledgments • we would like to thank the patients and investigators who participated in these clinical trials. • these clinical trials were sponsored by bristol myers squibb. professional medical writing from lisa feder, phd, and editorial assistance were provided by peloton advantage, llc, an open health company, parsippany, nj, usa, and were funded by bristol myers squibb. relationships and activities • awa: grants and personal fees: abbvie, bristol myers squibb, eli lilly, janssen, leo pharma, and novartis; personal fees: boehringer ingelheim/parexel, celgene, dermavant, genentech, glaxosmithkline, menlo therapeutics, merck, modernizing medicine, ortho dermatologics, pfizer, regeneron, sanofi genzyme, science 37, sun pharma, and valeant; grants: dermira, kyowa hakko kirin, and ucb, outside the submitted work • bs: honoraria or consultation fees: abbvie, almirall, amgen, arcutis, arena, aristea, asana, boehringer ingelheim, bristol myers squibb, connect biopharma, dermavant, eli lilly, equillium, glaxosmithkline, immunic therapeutics, janssen, leo pharma, maruho, meiji seika pharma, mindera, novartis, ortho dermatologics, pfizer, regeneron, sanofi genzyme, sun pharma, ucb, and ventyxbio; speaker: abbvie, eli lilly, janssen, and sanofi genzyme; scientific co-director (consulting fee): corevitas’ psoriasis registry; investigator: abbvie, cara, corevitas’ psoriasis registry, dermavant, eli lilly/dermira, and novartis • kbg: grant support and consulting fees: abbvie, boehringer ingelheim, bristol myers squibb, celgene, eli lilly, janssen, novartis, and ucb; consulting fees: amgen, almirall, dermira, leo pharma, pfizer, and sun pharma • jz, bb, rmk, jt, and jk: employees and shareholders: bristol myers squibb • kp: speakers bureau: abbvie, amgen, astellas, celgene, eli lilly, galderma, janssen, kyowa hakko kirin, leo pharma, merck sharp & dohme, novartis, pfizer, and valeant; grant/research support: abbvie, akros, allergan, amgen, anacor, arcutis, astrazeneca, baxalta, boehringer ingelheim, bristol myers squibb, celgene, coherus, dermira, dow pharma, eli lilly, galderma, genentech, glaxosmithkline, janssen, kyowa hakko kirin, leo pharma, medimmune, meiji seika pharma, merck serono, novartis, pfizer, regeneron, roche, sanofi genzyme, takeda, ucb, and valeant; consultant: abbvie, akros, amgen, arcutis, astellas, astrazeneca, baxalta, baxter, boehringer ingelheim, bristol myers squibb, canfite, celgene, coherus, dermira, dow pharma, eli lilly, forward pharma, galderma, genentech, janssen, kyowa hakko kirin, leo pharma, meiji seika pharma, merck serono, merck sharp & dohme, mitsubishi pharma, novartis, pfizer, regeneron, roche, sanofi genzyme, takeda, ucb, and valeant; honoraria: abbvie, akros, amgen, baxter, boehringer ingelheim, celgene, coherus, eli lilly, forward pharma, galderma, glaxosmithkline, janssen, kyowa hakko kirin, merck serono, merck sharp & dohme, novartis, pfizer, takeda, ucb, and valeant; scientific officer/steering committee/advisory board: abbvie, akros, amgen, anacor, astellas, baxter, boehringer ingelheim, bristol myers squibb, celgene, dow pharma, eli lilly, galderma, janssen, kyowa hakko kirin, merck serono, merck sharp & dohme, novartis, pfizer, regeneron, sanofi genzyme, and valeant presented at the fall clinical dermatology conference®; october 21—24, 2021; las vegas, nv, and virtual this is an encore of the 2021 eadv 30th congress poster this poster may not be reproduced without written permission from the authors.email for april w armstrong, md, mph: april.armstrong@med.usc.edu introduction • management of moderate psoriasis remains a signifi cant challenge, with some evidence suggesting patients with moderate disease are often undertreated and experience unsatisfactory clinical outcomes.1,2 however, there is a lack of consensus on how to defi ne moderate psoriasis, and no explicit guidelines exist for the treatment of this patient population. • apremilast (apr), an oral phosphodiesterase 4 inhibitor, is the fi rst new oral systemic, nonbiologic medication approved for the treatment of psoriasis in the past 20 years, and is approved in the united states for treatment of adult patients with active psoriatic arthritis (psa) and patients with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy.3 • given the lack of guidance for treating patients with moderate psoriasis and the recent availability of apr, the objectives of the current investigation were (1) to determine how dermatologists in the real-world clinical setting defi ne and treat moderate plaque psoriasis, and (2) to describe real-world clinical characteristics and 6-month treatment outcomes among patients with moderate psoriasis treated with apr. methods dermatologist survey • the survey portion of the investigation was conducted between october 2015 and july 2016. • us dermatologists treating patients with psoriasis were invited to complete an online survey which asked: – how they typically assess psoriasis severity – what cutoff criteria they use to defi ne moderate psoriasis – which treatments they commonly prescribe to patients with moderate plaque psoriasis • eligible survey participants were us dermatologists who: – treat ≥20 adult patients with plaque psoriasis per month, ≥1% of whom must be considered to have moderate psoriasis – spend ≥40% of practice time in medical dermatology or ≥70% in medical and surgical dermatology – have been in practice for 2 to 30 years – spend >75% of practice time in direct patient care prospective 6-month patient chart review • surveyed dermatologists were also asked to provide data from charts of 4 patients with a diagnosis of moderate plaque psoriasis whom they had seen in the last month, including ≥1 patient treated with apr; 6 months later they were invited to provide follow-up patient chart information. • the patients were required to meet the following criteria: – adult patient (≥18 years of age), diagnosed with plaque psoriasis and currently living – moderate disease severity (as determined by the surveyed, treating dermatologist) – seen by the dermatologist within the month before the dermatologist took the survey – using prescription topical or systemic medication for the treatment of moderate plaque psoriasis at the time of the survey methods (cont’d) • chart information included: – patient demographic characteristics – clinical disease characteristics – treatment patterns, including treatment shifts and discontinuations – effectiveness of treatment – safety and tolerability results dermatologist survey respondent dermatologists • a total of 150 dermatologists responded to the survey. • dermatologists had an average of 13.5 years in practice; most currently worked in a single-physician or multiphysician dermatology specialty practice (83%). they saw an average of 72 patients with psoriasis per month. scales used to assess psoriasis severity • the large majority of dermatologists (95%) reported they assessed disease severity based on the percentage of psoriasis-affected body surface area (bsa) (figure 1). – 59% of dermatologists responded that they also considered location of the affected area in their assessment of severity. figure 1. criteria used to assess psoriasis severity dermatology life quality index 0 20 40 60 80 100 physician global assessment psoriasis area and severity index patient assessment of their disease location of affected areas bsa 95% 17% 20% 25% 41% 59% location mentioned palms 88% genital area 85% feet 81% face 78% scalp 75% nails 50% legs 43% arms 42% dermatologist (n=150) response to questions: which of the following metrics do you use to determine if a patient has moderate plaque psoriasis? what locations do you use to determine if a patient has moderate plaque psoriasis? defi ning moderate plaque psoriasis • dermatologist-reported bsa cutoffs to defi ne moderate psoriasis varied widely, revealing a lack of consensus among dermatologists (median: 5% to 10%) (figure 2). results (cont’d) figure 2. dermatologist-reported bsa cutoffs for moderate psoriasis 0 overall range mean range d er m at ol og is tre po rt ed b sa su m m ar y st at is tic s (n = 14 2) psoriasis-affected bsa (%) median range 20 40 60 80 100 5–10 8–18 1–70 bsa low and high cutoff values reported by dermatologists who use bsa to assess disease severity (n=142) in response to the question: for the following metrics [including bsa], what are your typical cutoffs for moderate/severe psoriasis patients? please enter numbers for each. treatment of moderate plaque psoriasis • when asked to estimate what proportions of their patients with moderate plaque psoriasis receive various types of medications as their primary treatment, dermatologists reported that 47% were receiving biologic agents, 28% prescription topicals, 18% oral systemics, 5% phototherapy, and 2% over-the-counter (otc) topical agents (figure 3). figure 3. primary treatments for moderate plaque psoriasis proportion of patientsprimary treatment phototherapy 5% otc topical 2% prescription topical 28% oral systemics apr methotrexate acitretin cyclosporine 18% 7% 7% 3% 1% infliximab 0% biologics adalimumab ustekinumab etanercept secukinumab 47% 19% 13% 11% 4% dermatologist (n=150) response to the question: what percentage of your moderate plaque psoriasis patients are currently on the following types of treatment as their primary therapy? must add to 100%. 6-month prospective chart review of patients with moderate psoriasis treated with apr patient disposition and demographic/clinical features • the participating dermatologists identifi ed 270 patients with moderate psoriasis who had ≥1 follow-up visit within the 6-month follow-up period. among these, 70 patients who had ≥1 follow-up visit (mean visits=2) within the 6-month follow-up period were initially receiving apr. results (cont’d) • at the 6-month chart review, among patients treated with apr at baseline, 91% (64/70) remained on apr; 3 patients were new to apr (figure 4). • 65 patients (24%) were receiving apr as their primary therapy. • apr discontinuation occurred in 6 patients; reasons for discontinuation included loss of effi cacy (n=2), poor tolerability (n=3), and noncompliance (n=2); 1 patient discontinued due to both poor tolerability and noncompliance. figure 4. 6-month disposition of apr-treated patients 270 patients with moderate psoriasis with ≥1 visit within the 6-month follow-up period 200 patients were taking other therapies 70 patients were taking apr 6 discontinued apr 64 continuing apr 3 new to apr 67 patients currently taking apr • 1 patient switched from biologic + topical steroid • 2 patients added apr to topical • demographic and clinical characteristics of the patients receiving primary treatment with apr included in the current prospective chart review are summarized in table 1. • patients given apr had been treated by the responding dermatologists for a mean of 24.8 months, with offi ce visits occurring at a mean of every 2.8 months. table 1. demographic and clinical characteristics among patients with moderate psoriasis receiving apr as primary treatment characteristic patients with moderate psoriasis receiving apr as primary treatment* n=65 age, mean (range), years 47.3 (20–75) male, % 45 weight, mean (range), lb. 163.7 (130–245) race, % white 92 hispanic 3 african american 3 asian 2 employed full-time, % 62 any comorbidity, % 57 comorbidities in >5% of patients, % hypertension 23 obesity 9 dyslipidemia 19 diabetes§ 8 psa 9 depression 6 *primary therapy as defi ned by the surveyed dermatologist. §includes type 2 diabetes mellitus. results (cont’d) clinical effectiveness of apr treatment for moderate psoriasis • in patients receiving apr as their primary therapy, mean bsa changed from 9.9% at initial chart review to 4.9% at the 6-month chart review (figure 5). figure 5. change in bsa at 6 months with apr treatment 12 10 8 ps or ia si saf fe ct ed b sa (% ) 6 4 2 0 initial chart review 6-month chart review 9.9 4.9 • of patients receiving apr as their primary therapy, 54% were rated as having mild psoriasis at the 6-month chart review, marking a shift for these patients from moderate psoriasis at baseline (figure 6). figure 6. disease severity at 6 months, among patients with moderate psoriasis treated with apr mild note: 100% of patients were considered to have moderate disease severity at baseline moderate severe 5% 54% 42% data shown refl ect dermatologist (n=150) response to question: what would you consider to be this patient’s current disease severity level? note: percentages shown may not add to 100 because of rounding. • at the 6-month chart review, 65% of patients receiving apr as primary therapy were rated by dermatologists as having shown at least some improvement; 17% were rated as having shown signifi cant improvement (figure 7). • when asked about their clinical experience with apr, 68% of dermatologists stated that apr exceeded or met their expectations. results (cont’d) figure 7. dermatologist assessment of condition change at 6 months in patients treated with apr seen significant improvement seen moderate improvement seen some improvement been stable deteriorated 17% 34% 31% 17% 2% data shown refl ect dermatologist (n=150) response to the question: how has this patient’s condition changed over the past 6 months? note: percentages shown may not add to 100 because of rounding. side effects with apr reported during the 6-month chart review period • among patients with available safety information, 8/66 (12%) reported side effects during treatment; these included diarrhea (n=5), nausea (n=3), abdominal pain (n=3), and headache (n=1). – all side effects were considered mild, except 1 case of diarrhea that was considered moderate; 2 patients took loperamide to manage diarrhea. • on average, side effects resolved within 2 weeks, with the exception of abdominal pain, which persisted for an average of 7 weeks. • 1 patient temporarily discontinued apr because of diarrhea but was re-initiated and continued on treatment. conclusions • in the real-world clinical setting, widely varying bsa cutoff values to identify moderate psoriasis reveal a lack of consensus surrounding the defi nition of moderate psoriasis among us dermatologists. • based on patient chart review, apr is well tolerated and effective for treatment of moderate psoriasis. references 1. armstrong aw, et al. jama dermatol. 2013;149:1180-1185. 2. lebwohl mg, et al. j am acad dermatol. 2014;70:871-881. 3. otezla [package insert]. summit, nj: celgene corporation; june 2017. acknowledgment the authors acknowledge fi nancial support for this study from celgene corporation. the authors received editorial support in the preparation of this report from amy shaberman, phd, of peloton advantage, llc, parsippany, nj, usa, funded by celgene corporation, summit, nj, usa. the authors, however, directed and are fully responsible for all content and editorial decisions for this poster. correspondence melissa l. f. knuckles – mlfk@aol.com disclosures mlfk: abbvie, allergan, amgen, celgene corporation, eli lilly, galderma, novartis, and sun pharma – advisory board member, consultant, and/or speaker. abbvie, amgen, bayer, biogen, crown labs, eli lilly, johnson and johnson, leo pharma, and medimetriks – investigator. el: celgene corporation – employment. js: abbvie, allergan, amgen, celgene corporation, eli lilly, genentech, genzum, janssen, kadmon, merz, pfi zer, and regeneron – advisory board member, investigator, and/or speaker. presented at: the 2017 fall clinical dermatology conference; october 12–15, 2017; las vegas, nv. defi ning and treating moderate plaque psoriasis in a real-world clinical setting: a dermatologist survey and prospective 6-month chart review of patients treated with apremilast melissa l. f. knuckles, md, psc1; eugenia levi, pharmd2; jennifer soung, md3 1melissa l. f. knuckles, m.d., p.s.c. dermatology, richmond, ky; 2celgene corporation, summit, nj; 3southern california dermatology, santa ana, ca fc17postercelgeneknucklesdefiningtreatingmpp.pdf skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 65 brief article an unusual timeline of nivolumab-induced vitiligo in a patient with melanoma renat ahatov, bsa1, allison good, md2, lindy ross, md2 1the university of texas medical branch school of medicine in galveston, tx 2the university of texas medical branch department of dermatology in galveston, tx. vitiligo is an autoimmune disorder of the skin, marked by depigmentation of the skin, due to the autoimmune loss of melanocytes. vitiligo has been reported to occur in up to 25% of the patients on programmed cell death–1 receptor (pd1) inhibitors.1 pd-1 ligand is produced by some cancer cells as a means of immune system evasion. pd-1 ligand binds to pd-1, which leads to t-cell inactivation that allows the cancer to proliferate unchecked by the immune system. nivolumab is a humanized igg4 anti–pd-1 monoclonal antibody that prevents t-cell inactivation. it is an fdaapproved treatment for unresectable/metastatic melanoma, along with various other malignancies.2 the vitiligo seen with nivolumab has been theorized to be due to the destruction of non-cancerous melanocytes by activated t-cells. this side effect of nivolumab has been associated with more favorable outcomes in melanoma, as it correlates to a strong immune response against tumor cells. a previous study found that vitiligo typically presents 2 to 9 months after starting nivolumab, with an average presentation onset of 5.2 months.3 we present a case of a patient who was started on nivolumab for his melanoma and developed vitiligo one year after beginning pd-1 inhibitor therapy around the time of his final nivolumab cycle, which is later onset than previously reported in the literature. in addition, the vitiligo continued to progress after treatment with nivolumab was completed, which has not been previously reported with nivolumabassociated vitiligo. abstract vitiligo, manifested by skin hypopigmentation, is an autoimmune disorder of the skin due to the autoimmune destruction of melanocytes. nivolumab, which is a programmed cell death–1 receptor inhibitor, is a well-known therapy for melanoma. nivolumab-induced vitiligo has been described in literature, explained by destruction of non-cancerous melanocytes. this is considered a favorable response, due to a correlated stronger immune response against tumor cells. the average onset of the vitiligo is reported to be 5.2 months after starting the therapy, with a maximum reported onset being 9 months. we present a 52-year-old male patient whose initial vitiligo presentation occurred a year after starting the therapy and has continued for months after concluding nivolumab therapy. introduction case report skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 66 a 52-year-old male with superficial spreading melanoma stage iiia t2n2m0 was treated with wide local excision of the tumor and sentinel lymph node biopsy. two lymph nodes were involved with metastatic melanoma, and nivolumab therapy was initiated. the patient was started on nivolumab therapy one month after the excision and completed the therapy one year later with no evidence of tumor recurrence or metastasis. two months after completion of nivolumab, the patient was seen at a follow-up visit. the patient noted the development of an asymptomatic depigmented patch on his right cheek that started one year after starting the nivolumab therapy, about the time the therapy was completed (figure 1). figure 1. depigmentation noted on the right cheek approximately 14 months after initiating nivolumab the patient’s thyroid stimulating hormone level was within normal limits. he had no personal or family history of vitiligo, and he had no halo nevi. the patient was seen for follow-up three months later, at which point he noted that the depigmented patch had continued to spread to his forehead, scalp, and left cheek (figure 2). he also reported that the right cheek became erythematous with sun exposure. on physical exam, depigmented patches were present on both cheeks and forehead, with erythema within the depigmented patch of the right cheek. approximately four months later, the patient did not see significant improvement in the depigmentation and had a new depigmented macule on his left forearm. no sign of melanoma recurrence has been noted and no evidence of other immune-related side effects were noted. the patient is currently continuing to be closely monitored for presumed post-nivolumab vitiligo. patient declined treatment with topical steroids, but has gotten low levels of ambient sun exposure and has noticed re-pigmentation of the cheek and scalp at one-year follow-up appointment. pd-1 inhibitors and their associations with various cutaneous phenomena have been well described in the literature. some of these include lichenoid dermatosis, eczema, vitiligo, and steven-johnson syndrome.4 the pathophysiology of vitiligo is the discussion skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 67 figure 2. a) increased depigmentation noted on the right cheek and newly developed depigmentation on b) forehead and scalp approximately 17 months after initiating the therapy. autoimmune destruction of epidermal melanocytes caused by t-cell infiltration. vitiligo is often associated with other autoimmune diseases such as lupus, autoimmune thyroiditis, and addison disease, but it can also occur with immunotherapy usage.5,6 with pd-1 inhibitors, it is postulated that the healthy melanocytes are targeted due to the overlapping antigens on the normal melanocytes with those on the melanoma cells. therefore, it is associated with a tumor response in melanoma therapy, as it indicates an adequate response to the pd-1 inhibitor therapy.3 vitiligo is most commonly seen when nivolumab is used for melanomas. however, cases of vitiligo in other cancers treated by nivolumab have also been reported, including lung cancer, renal cancer, and leukemia.4,5,7 the average time until vitiligo presentation after starting nivolumab therapy was reported to be 5.2 months in a prior study. while the sample size in that study was nine patients, previous cases in the literature report vitiligo developing 9 months or less after the initiation of nivolumab.3,5 in our patient, the vitiligo on his right cheek began about one year after starting nivolumab and continued to progress after the completion of nivolumab therapy. while it is possible that the vitiligo began less than one year after beginning therapy as this timeframe was patient-reported, the continued progression of the vitiligo while no longer on nivolumab is unusual and may be explained by sustained antitumor t cell activity induced by nivolumab therapy. it is also possible that melanoma itself may cause vitiligolike lesions, but the patient continues to have no signs of disease progression with regular follow-up. currently, there are no guidelines for the treatment for this post-immunotherapy vitiligo, but observation and treatment with topical corticosteroids, calcineurin inhibitors, and phototherapy can be recommended. although vitiligo is a b a skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 68 benign condition, it can be psychologically stressful to the patient, especially as it relates to a serious disease such as melanoma. therefore, psychiatric support, such as counseling, can also be offered as needed.8 in this case, the patient declined treatment because the vitiligo was not cosmetically bothersome to him. close observation will be continued. this case highlights the possibility of post-immunotherapy vitiligo occurring much later than the previously reported average of 5.2 months after starting nivolumab therapy. the case is also unique in its continued progression of vitiligo after completion of nivolumab. conflict of interest disclosures: none funding: none corresponding author: allison good, md pgy-2 dermatology resident university of texas medical branch at galveston department of dermatology 301 university blvd, 4.112 mccullough bldg galveston, tx 77555-1327 phone: (573) 808-0425 fax: (409) 772-4456 e-mail: ajgood@utmb.edu references: 1. hua c, boussemart l, mateus c, routier e, boutros c, cazenave h, viollet r, thomas m, roy s, benannoune n, tomasic g, soria jc, champiat s, texier m, lanoy e, robert c. association of vitiligo with tumor response in patients with metastatic melanoma treated with pembrolizumab. jama dermatol. 2016 jan;152(1):45-51. 2. koppolu v, rekha vasigala vk. checkpoint immunotherapy by nivolumab for treatment of metastatic melanoma. j cancer res ther. 2018 oct-dec;14(6):1167-1175. 3. nakamura y, tanaka r, asami y, teramoto y, imamura t, sato s, maruyama h, fujisawa y, matsuya t, fujimoto m, yamamoto a. correlation between vitiligo occurrence and clinical benefit in advanced melanoma patients treated with nivolumab: a multi-institutional retrospective study. j dermatol. 2017 feb;44(2):117-122. 4. yin es, totonchy mb, leventhal js. nivolumab-associated vitiligo-like depigmentation in a patient with acute myeloid leukemia: a novel finding. jaad case rep. 2017;3(2):90-92. 5. lolli c, medri m, ricci m, et al. vitiligo-like lesions in a patient treated with nivolumab for renal cell carcinoma. medicine (baltimore). 2018;97(52):e13810. 6. frisoli ml, essien k, harris je. vitiligo: mechanisms of pathogenesis and treatment. annu rev immunol. 2020 apr 26;38:621-648. 7. kosche c, mohindra n, choi jn. vitiligo in a patient undergoing nivolumab treatment for non-small cell lung cancer. jaad case rep. 2018 nov 10;4(10):1042-1044. 8. edmondson la, smith lv, mallik a. nivolumab-induced vitiligo in a metastatic melanoma patient: a case report. j oncol pharm pract. 2017 dec;23(8):629-634. conclusion mailto:ajgood@utmb.edu first “real-world” insights on apremilast treatment for patients with plaque psoriasis from the lapis-pso study: an interim analysis kristian reich, md1; stefanie bomas, md2; bernhard korge, md3; maria manasterski, md4; uwe schwichtenberg, md5; hannah mentz, phd6; kathrin groegel, phd6; natalie núnez gómez, md6 1dermatologikum hamburg and sciderm research institute, hamburg, germany; 2praxis dr. med. s. rotterdam, gelsenkirchen-feldmark, germany; 3priv. doz. dr. med. korge, düren, germany; 4hautarztpraxis manasterski und dues, berlin, germany; 5derma nord hautarztpraxen dr. med. schwichtenberg, bremen, germany; 6celgene gmbh, munich, germany introduction • this national, multicenter, prospective, noninterventional study is assessing long-term treatment with apremilast in patients with plaque psoriasis in germany (lapis-pso; clinicaltrials.gov: nct02626793). • this study aims to determine patients’ quality of life and satisfaction with apremilast 30 mg twice daily (apr) treatment, as well as the clinical effi cacy of apr, in a real-world setting of patients who have previously received conventional systemic therapy. • a subgroup analysis of the lapis-pso interim analysis is presented here. methods study design • the subgroup analysis was stratifi ed based on the number of prior conventional systemic treatments (≤1 vs. >1) (table 1). • scope: baseline until visit 2 (~4 months), n=111 (figure 1) • patients: moderate to severe plaque psoriasis (n=500, 100 sites planned) – indication and inclusion according to apremilast summary of product characteristics1 – patients previously treated with biologics were not observed • no strict visit schedule was performed; visits were timed according to clinical practice. figure 1. study design 0 1 2 3 4 5 6 7 8 9 10 11 12 13 visit 5 end of observationvisit 4visit 3 visit 1 optional visit 0 bl patients (%) with dlqi score ≤5 or dlqi improvement by ≥5 points vs. baseline (bl) time [≈ months]primary end point visit 2 stratifi cation • two subgroups were defi ned following stratifi cation: – subgroup 1: patients with treatment failure (lack of effi cacy or intolerance) of ≤1 prior conventional systemic treatment – subgroup 2: patients with treatment failure (lack of effi cacy or intolerance) of >1 prior conventional systemic treatment end points primary end point • the primary end point was the percentage of patients achieving dermatology life quality index (dlqi) score ≤5 or improvement from baseline in dlqi score by ≥5 points at visit 2. secondary end points (interim analysis at visit 2) • percentage of patients achieving dlqi score ≤5 or improvement from baseline in dlqi score by ≥5 points at all other visits • effi cacy on skin: physician’s global assessment (pga) and body surface area (bsa) involvement • in addition, the following were assessed: – scalp involvement – nail involvement – patient’s global assessment (paga) • safety and tolerability results patient demographics and disease characteristics • baseline patient demographics and disease characteristics for the full analysis set (fas) are shown in table 1. table 1. baseline patient demographics and disease characteristics characteristic subgroup 1 (≤1 prior conventional systemic) n=43 subgroup 2 (>1 prior conventional systemic) n=30 male (%) 51.2 43.3 age at inclusion, mean (sd), years 49.2 (13.22) 53.3 (12.99) body mass index, mean (sd), kg/m2 27.74 (5.21) 28.37 (5.92) age at initial diagnosis, mean (sd), years 32.1 (17.01) 27.7 (12.54) scalp involvement, n (%) 36 (83.7) 27 (93.1) nail involvement, n (%) 21 (48.8) 15 (50.0) number of affected nails, mean (sd) 6.6 (3.82; n=17) 6.1 (3.50; n=13) palmoplantar involvement, n (%) 11 (26.2) 6 (20.7) pga score, mean (sd) 3.1 (0.86) 3.2 (0.63) paga score, mean (sd) 3.0 (0.92) 3.4 (0.57) results (cont’d) dlqi response • characteristics at baseline were comparable (mean [sd] dlqi score was 14.6 [6.31]; n=73). • the percentage of patients achieving dlqi score of ≤5 or dlqi improvement from baseline by ≥5 (primary end point) was 65.8% in subgroup 1 vs. 61.5% in subgroup 2 (table 2). table 2. dlqi response at visit 2: stratifi cation (fas) stratifi cation achievement of dlqi score ≤5 or dlqi improvement from bl by ≥5, n/n (%) achievement of dlqi score ≤5, n/n (%) change from bl in dlqi score, mean (sd) subgroup 1 (≤1 prior conventional systemic) 25/38 (65.8) 22/38 (57.9) −8.3 (8.09) subgroup 2 (>1 prior conventional systemic) 16/26 (61.5) 9/26 (34.6) −6.4 (5.94) pga and paga response • a higher percentage of patients achieved pga and paga scores of 0 or 1 at visit 2 in subgroup 1 (30.8% and 36.8%, respectively) compared with subgroup 2 (22.2% and 22.2%, respectively) (figure 2). figure 2. pga and paga* response of 0 or 1 at visits 1 and 2 17.9 13.2 30.8 36.8 0 5 10 15 20 25 30 35 40 10.7 3.7 22.2 22.2 0 5 10 15 20 25 30 35 40 subgroup 1 (≤1 prior conventional systemic) subgroup 2 (>1 prior conventional systemic) pga (0 or 1) paga (0 or 1) pga (0 or 1) paga (0 or 1) 7/39 5/38 3/28 1/2712/39 14/38 6/27 6/27n/n= visit 1 visit 2 pa tie nt s ac hi ev in g re sp on se (% ) pa tie nt s ac hi ev in g re sp on se (% ) *the pga and paga are 5-point scales ranging from 0 (clear), 1 (almost clear), 2 (mild), 3 (moderate), to 4 (severe). effi cacy on nail psoriasis: target-nail psoriasis severity index (target-napsi) • the mean (sd) target-napsi in subgroup 1 (4.0 [2.06]) was better than that in subgroup 2 (4.6 [2.53]). • the mean (sd) percentage change in target-napsi was −58.22% (53.423) in subgroup 1 and −48.61% (37.241) in subgroup 2. • target-napsi-50 response was identical between subgroups at visit 2 (66.7%) (figure 3). figure 3. target-napsi-50 response subgroup 1 (≤1 prior conventional systemic) subgroup 2 (>1 prior conventional systemic) n/n= 0 10 20 30 40 50 60 70 80 0 10 20 30 40 50 60 70 80 pa tie nt s ac hi ev in g re sp on se (% ) pa tie nt s ac hi ev in g re sp on se (% ) visit 2 12/18 visit 1 5/18 visit 2 8/12 visit 1 2/12 66.7 27.8 66.7 16.7 • scalp manifestation was comparable at baseline and had slightly greater improvements in subgroup 1 at ~4 months. safety • the overall incidence of aes (table 3) is lower than that in clinical studies. • only 1 patient was affected by severe aes (obstipation, tremor, palpitations). results (cont’d) table 3. overview of adverse events patients, n (%) subgroup 1 n=61 subgroup 2 n=47 ≥1 ae 14 (23.0) 13 (27.7) ≥1 ae (apr treatment-related) 11 (18.0) 7 (14.9) ≥1 ae leading to drug withdrawal 6 (9.8) 3 (6.4) ≥1 sae (apr treatment-related: disorders of the nervous system: tremor and heart diseases: palpitations) 1 (1.6) 0 (0.0) ae=adverse event; sae=serious adverse event. • the most common ae was diarrhea (8.3%) (table 4). table 4. most common adverse events patients,* n (%) sap n=108 diarrhea 9 (8.3) nausea 2 (1.9) upper respiratory tract infection 1 (0.9) headache 2 (1.9) *most common aes that occurred in ≥5% of patients in phase 3 clinical trials of apremilast. interim analysis includes total number of saes and related aes. nonserious aes were asked to be reported upon termination. sap=safety analysis population (all patients who received ≥1 dose of apr and fulfi lled the inclusion criteria). conclusions • the lapis-pso interim analysis presents the fi rst data on apr for the treatment of patients with moderate to severe plaque psoriasis under routine clinical care in germany. • this interim analysis suggests that the effi cacy of apr in daily practice is comparable to clinical trial results and responses may be improved in patients who have received fewer prior conventional systemic therapies. • patient quality of life is rapidly and signifi cantly improved by apr (as shown by dlqi response within 4 weeks at visit 1). • the safety profi le in this real-world setting was consistent with clinical trials of apr in psoriasis.2,3 • there was a signifi cant improvement in disease in both subgroups. references 1. otezla 30mg tablets. summary of product characteristics. uxbridge, uk: celgene ltd; january 2017. 2. papp k, et al. j am acad dermatol. 2015;73:37-49. 3. paul c, et al. br j dermatol. 2015;173:1387-1399. acknowledgments the authors acknowledge fi nancial support for this study from celgene corporation. the authors received editorial support in the preparation of this report from amy shaberman, phd, of peloton advantage, llc, parsippany, nj, usa, funded by celgene corporation, summit, nj, usa. the authors, however, directed and are fully responsible for all content and editorial decisions for this poster. correspondence kristian reich – kreich@dermatologikum.de disclosures kr: abbvie, amgen, biogen, boehringer ingelheim, celgene corporation, centocor, covagen, eli lilly, forward pharma, glaxosmithkline, janssen-cilag, leo pharma, medac, merck sharp & dohme corp, novartis, ocean pharma, pfi zer (wyeth), regeneron, takeda, ucb pharma, and xenoport – honoraria as a consultant and/or advisory board member and/or acted as a paid speaker and/or participated in clinical trials. sb: no confl icts or potential confl icts of interest to disclose. bk: no confl icts or potential confl icts of interest to disclose. mm: abbvie, janssen, and novartis – paid consultant or study investigator. us: abbvie deutschland gmbh, almirall hermal gmbh, astellas pharma gmbh, beiersdorf derma medical gmbh, celgene gmbh, janssen cilag gmbh, johnson & johnson gmbh, leo pharma gmbh, l´oréal gmbh, meda pharma gmbh, merz pharmaceuticals gmbh, msd sharp & dohme gmbh, novartis pharma gmbh, pfi zer gmbh, and medical project design gmbh – paid speaker, advisory board member, investigator, and/or stockholder. hm, kg & nng: celgene gmbh – employment. presented at: the 2017 fall clinical dermatology conference; october 12–15, 2017; las vegas, nv. fc17postercelgenereichfirstrealworld.pdf synopsis • psoriasis is a chronic, systemic, immune-mediated disease of the skin that affects > 7.4 million people in the united states, with an estimated prevalence of 2% to 4%1 • secukinumab is a fully human monoclonal antibody that selectively neutralizes interleukin (il)-17a and has shown long-lasting efficacy and safety in the treatment of the complete spectrum of psoriasis manifestations, including nail, scalp, and palmoplantar psoriasis and psoriatic arthritis2-8 • there remains limited information on the effectiveness of secukinumab treatment in patients with plaque psoriasis in us real-world settings objective • to describe real-world effectiveness outcomes in us patients with plaque psoriasis who initiated secukinumab in clinical practice, using clinical data obtained from the modernizing medicine data services (mmds) electronic medical records (emrs) dermatology panel methods study design and patient population • all data were collected from modernizing medicine’s electronic medical assistant (ema) system – ema delivers structured, real-world data captured from > 500,000 unique patients with psoriasis – data from emrs for patients in the united states with a clinical diagnosis of psoriasis were deidentified in accordance with hipaa (health insurance portability and accountability act) for research use • eligible patients in the mmds database had a diagnosis of plaque psoriasis during the study period of july 1, 2014, to march 31, 2018, had ≥ 1 prescription order for secukinumab within the index period (january 1, 2015, to september 30, 2017), and were aged ≥ 18 years at the time of secukinumab initiation (index date) • patients had ≥ 1 clinical visit for any reason during the 6-month pre-index (baseline) period and ≥ 1 clinical visit for any reason within each of the first and second 6 months following secukinumab initiation study variables and data analysis • outcomes were assessed in two cohorts: patients who had ≥ 6 months of follow-up and those who had ≥ 12 months of follow-up • demographic characteristics (age, sex, race, body weight, us region), treatment history (during 6-month pre-index period only), and clinical characteristics (comorbidities, psoriasis subtype, body surface area [bsa], and physician global assessment [pga]) were assessed by dermatology providers during the 6-month baseline period • mean (sd) and categorical bsa and physician global assessment (pga) scores were evaluated during the 6-month baseline period and at 6-month (window, 5-7 months) and 12-month (window, 11-13 months) follow-up visits among patients with scores reported at baseline and follow-up • categorical changes from baseline to 6and 12-month follow-up visits were calculated among patients with both baseline and follow-up bsa and pga measurements available secukinumab is associated with improvements in real-world effectiveness outcomes through 12 months of follow-up in patients with plaque psoriasis: analysis of us dermatology electronic medical records paul s. yamauchi, md, phd,1 chi-chang chen, phd,2 yao ding, phd,2 rebecca germino, phd3 1ucla school of medicine, santa monica, ca; 2iqvia, plymouth meeting, pa; 3novartis pharmaceuticals corporation, east hanover, nj scan qr code to download this poster. presented at the 2019 winter clinical dermatology conference; january 18-23, 2019; koloa, hi. your document will be available for download at the following url: url: http://novartis.medicalcongressposters.com/default.aspx?doc=dc28a and via text message (sms) text: qdc28a to: 8nova (86682) us only +18324604729 north, central and south americas; caribbean; china +447860024038 uk, europe & russia +46737494608 sweden, europe note: downloading data may incur costs which can vary depending on your service provider and may be high if you are using your smartphone abroad. please check your phone tariff or contact your service provider for more details. disclosures p. s. yamauchi has served as an investigator for amgen, celgene, dermira, galderma, janssen, leo pharma, eli lilly, medimmune, novartis, pfizer, regeneron, and sandoz and has served as an advisor and/or speaker for abbvie, amgen, baxter, celgene, dermira, galderma, janssen, leo pharma, eli lilly, novartis, pfizer, and regeneron. c.-c. chen and y. ding are employees of iqvia who received consulting fees to conduct this research. r. germino is an employee of novartis pharmaceuticals corporation. acknowledgments support for third-party writing assistance for this poster, furnished by meaghan paganelli, phd, of health interactions, inc, was provided by novartis pharmaceuticals corporation, east hanover, nj. this study was sponsored by novartis pharmaceuticals corporation, east hanover, nj. © 2018 novartis pharmaceuticals corporation. results patient demographics • among all patients who initiated secukinumab with 6 months (n = 6568) and 12 months of follow-up (n = 4996), the mean (sd) age was 51.1 (13.9) and 51.6 (13.7) years, respectively, 50.6% and 50.5% were male, and all us geographic regions were represented (table 1) table 1. demographics, clinical characteristics, and treatment history of patients with psoriasis who initiated secukinumab and had 6 months or 12 months of follow-up characteristic patients with 6-month follow-up (n = 6568) patients with 12-month follow-up (n = 4996) age, mean (sd), years 51.1 (13.9) 51.6 (13.7) male, n (%) 3326 (50.6) 2524 (50.5) us region, n (%) south 2734 (41.6) 2070 (41.4) west 1428 (21.7) 1080 (21.6) midwest 1355 (20.6) 1036 (20.7) northeast 1040 (15.8) 802 (16.1) unknown 1828 (27.8) 8 (0.2) race white 4270 (65.0) 3317 (66.4) black 187 (2.9) 141 (2.8) asian 163 (2.5) 129 (2.6) hispanic 120 (1.8) 92 (1.8) other/unknown 1828 (27.8) 1317 (26.4) comorbidities, n (%) hypertension 1926 (29.3) 1487 (29.8) psoriatic arthritis 1443 (22.0) 1110 (22.2) diabetes 1122 (17.1) 877 (17.6) hyperlipidemia 953 (14.5) 751 (15.0) malignancies 782 (11.9) 633 (12.7) coronary heart disease 169 (2.6) 125 (2.5) cerebrovascular disease* 80 (1.2) 70 (1.4) obesity 65 (1.0) 55 (1.1) rheumatoid arthritis 26 (0.4) 24 (0.5) treatment history prior biologic treatment preceding secukinumab claim, n (%) tumor necrosis factor inhibitors† 1469 (54.6) 1148 (54.1) ustekinumab 1250 (46.5) 1011 (47.6) il-17a inhibitors‡ 103 (3.8) 69 (3.3) il, interleukin. * cerebrovascular disease included hemorrhagic stroke and transient ischemic attack. † tumor necrosis factor inhibitors included adalimumab, certolizumab pegol, etanercept, golimumab, and infliximab. ‡ il-17 inhibitors included brodalumab and ixekizumab. change in clinical effectiveness outcomes from secukinumab initiation • among patients with plaque psoriasis in the mmds database who initiated secukinumab and had baseline bsa and pga values, 792 and 472 patients, respectively, had bsa measurements, and 741 and 441 patients, respectively, had pga scores at 6 and 12 months • the mean bsa decreased from 20.1% at baseline to 11.1% at 6 months and from 21.4% at baseline to 11.4% at 12 months (figure 1a) – the proportion of patients who had mild disease (bsa < 3%) increased from 10.7% (85 of 792 patients) at baseline to 38.1% (302 of 792) at 6 months and from 9.8% (46 of 472 patients) to 37.9% (179 of 472) at 12 months (figure 1b) – the proportion of patients with severe disease (bsa > 10%) decreased from 49.6% (393 of 792 patients) at baseline to 26.5% (210 of 792) and from 51.3% (242 of 472 patients) to 28.6% (135 of 472) at 12 months figure 1. (a) mean and (b) categorical bsa* change in patients who initiated secukinumab and had 6 months and 12 months of follow-up bsa, affected body surface area. * available effectiveness records for bsa were reported based on the index visit or the visit closest to the index with such values during the 6-month baseline period. † baseline data were from the patients who enrolled and had 6or 12-month follow-up periods, respectively. figure 2. (a) mean and (b) categorical pga* change in patients who initiated secukinumab and had 6 months and 12 months of follow-up pga, physician global assessment. * available effectiveness records for pga scores were reported based on the index visit or the visit closest to the index with such values during the 6-month baseline period. † baseline data were from the patients who enrolled and had 6or 12-month follow-up periods, respectively. categorical bsa a b 20.1 n = 792 11.1 n = 792 21.4 n = 472 11.4 n = 472 0 5 10 15 20 25 30 m ea n va lu e ,% overall bsa baseline† 6-month follow-up 12-month follow-up mild (< 3%) moderate (3%–10%) severe (> 10%) .0 0 10 20 30 40 50 60 70 80 90 100 baseline (n = 792) 6-month follow-up (n = 792) baseline (n = 472) 12-month follow-up (n = 472) p ro po rt io n of p at ie nt s, % 10.7 n = 85 38.1 n = 302 9.8 n = 46 37.9 n = 179 39.7 n = 314 35.4 n = 280 39 n = 184 33.5 n = 158 49.6 n = 393 26.5 n = 210 51.3 n = 242 28.6 n = 135 a b m ea n va lu e ,% overall pga baseline† 6-month follow-up 12-month follow-up clear/minimal (0–1) mild/moderate (2–3) marked/severe (4–5) p ro po rt io n of p at ie nt s, % 0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5 14.0 n = 104 46.8 n = 347 14.1 n = 62 39.9 n = 176 60.3 n = 447 45.5 n = 337 58.3 n = 257 49.7 n = 219 25.6 n = 190 7.7 n = 57 27.7 n = 122 10.4 n = 46 0 10 20 30 40 50 60 70 80 90 100 baseline (n = 741) 6-month follow-up (n = 741) baseline (n = 441) 12-month follow-up (n = 441) categorical pga 2.9 n = 741 1.7 n = 741 2.9 n = 441 2.0 n = 441 • the mean pga score decreased from 2.9 to 1.7 at 6 months and from 2.9 to 2.0 at 12 months (figure 2a) • the proportion of patients who achieved a pga score of 0/1 (clear/minimal disease) increased from 14.0% (104 of 741 patients) at baseline to 46.8% (347 of 741) at 6 months and from 14.1% (62 of 441 patients) to 39.9% (176 of 441) at 12 months (figure 2b) limitations • the mmds database included data captured only from physicians contributing to the emr network (that was then de-identified), and results may not be generalizable to all patients with psoriasis • no continuous health plan enrollment information was captured in the emr database • patients with comorbid psoriatic arthritis or ankylosing spondylitis initiating secukinumab were not excluded from the study population, leading to potential confounding variables • this study was retrospective in nature and relied on coding to make associations between secukinumab exposure and effectiveness outcomes conclusion • in this analysis of real-world data among patients with plaque psoriasis, secukinumab treatment increased the proportion of patients who achieved bsa < 3% and pga scores of 0-1 by 3to 4-fold after 6 months, with similar improvements shown through 12 months • these findings highlight the real-worldeffectiveness of secukinumab in improving skin clearance in patients with mostly moderate-to-severe disease and are consistent with previous real-world studies references 1. rachakonda td, et al. j am acad dermatol. 2014;70(3):512-6. 2. langley rg, et al. n engl j med. 2014;371(4):326-38. 3. blauvelt a, et al. br j dermatol. 2015;172(2):484-93. 4. paul c, et al. j eur acad dermatol venereol. 2015;29(6):1082-90. 5. thaci d, et al. j am acad dermatol. 2015;73(3):400-9. 6. armstrong aw, et al. j clin aesthet dermatol. 2016;9(6 suppl 1):s12-6. 7. mease p, et al. ann rheum dis. 2018;77(6):890-7. 8. bagel j, et al. poster presented at: 27th european academy of dermatology and venereology congress; september 12, 2018; paris, france [eposter p1850]. • the most common comorbidities were hypertension, psoriatic arthritis, and diabetes (table 1) • overall, in both groups, approximately 40% of patients received prior biologic treatment during the 6-month baseline period (table 1) mahmoud a. ghannoum1,2 janet herrada1, ahmed gamal1,2, lisa long1,2, thomas s. mccormick2, and ayman grada3 1university hospital cleveland medical center, center for medical mycology, 2case western reserve university, department of dermatology and 3r&d and medical affairs, almirall us, malvern, pa, usa *corresponding author: mahmoud ghannoum, phd, mba, faam, fidsa table 1. susceptibility testing results for sarecycline and minocycline against healthy gut microbes (µg/ml, n=28) • in this study, sarecycline demonstrated less activity against 79% of the microorganisms normally found in a healthy human gut, when compared to minocycline • sarecycline is a narrow-spectrum antibiotic • our data suggests that sarecycline may have less impact on disrupting commensal and symbiotic organisms residing in the gut and is less likely to promote dysbiosis. in vivo evaluation is ongoing • sarecycline showed significantly less activity against e. coli compared to minocycline at all time points (pvalues <0.05) • sarecycline was significantly less active against c. tropicalis compared to minocycline at 20 and 22 hours post exposure (p-values <0.05) • time kill study shows that with longer time exposure sarecycline has less inhibitory activity against candida • sarecycline showed significantly less activity against l. paracasei compared to minocycline after 24 hours of growth (p-value of 0.002) • sarecycline showed significantly less activity against b. adolescentis compared to minocycline after 48 hours of growth (p-value of 0.042) objective evaluate the effect of sarecycline, a narrow spectrum antibiotic, compared to minocycline, a broad-spectrum antibiotic, against a panel of microorganisms that reflect the diversity of the gut microbiome using in vitro minimum inhibitory concentration (mic) testing and timekill kinetic assays. 1. chose representative bacterial and fungal strains found in the healthy gut 2. perform antimicrobial susceptibility testing minimum inhibitory concentration (mic) testing was performed using modified clinical laboratory standards institute methodology 3. establish growth curves e. coli and candida tropicalis were selected as representative of aerobic bacteria and yeast, respectively. while lactobacillus paracasei and bifidobacterium adolescentis were selected as representative of anaerobic bacteria that colonize the gut. methods compared to minocycline, sarecycline showed significantly less antimicrobial activity against: • 10 of 12 isolates from the bacteroidetes phylum • 3 out of 4 isolates from actinobacteria phylum • 5 of 7 isolates from the firmicutes phylum, e. coli • propionibacterium freudenreichii (≥ 3 dilutions) • sarecycline also showed less activity against 2 candida species this study was supported by almirall, llc, malvern, pa higher fold difference indicates lower sarecycline activity 0.00 0.10 0.20 0.30 0.40 0.50 0.60 0.70 0.80 0 2 4 6 20 22 a ve ra ge  o d  ± sd hours post inoculation escherichia coli sarecycline minocycline growth control * * * * * 0.00 0.10 0.20 0.30 0.40 0.50 0.60 0.70 0.80 0 2 4 6 20 22 a ve ra ge  o d  ± sd hours post inoculation candida tropicalis sarecycline minocycline growth control ** 4 4.5 5 5.5 6 6.5 7 0 2 4 8 24 a ve ra ge  l og  c fu  ± sd hours post inoculation lactobacillus paracesi sarecycline minocycline growth control * 4 4.5 5 5.5 6 6.5 7 7.5 8 0 2 4 8 24 48 a ve ra ge  l og  c fu  ± sd hours post inoculation bifidobacterium adolescentis sarecycline minocycline growth control * figure 1. and 2. effect of sarecycline vs. minocycline on the growth rates of aerobic microorganisms figure 3. and 4. effect of sarecycline vs. minocycline on the growth rates of anaerobic microorganisms sarecycline demonstrated reduced activity against representative bacterial and fungal microflora commonly present in the human gastrointestinal tract phylum genus species sarecycline minocycline fold difference in mic actinobacteria bifidobacterium bifidobacterium adolescentis 1 1 1 actinobacteria collinsella collinsella aerofaciens 1 0.5 2 actinobacteria eggerthella eggerthella lenta 1 0.5 2 actinobacteria actinomycetales propionibacterium freudenreichii 8 1 8 bacteroidetes bacteroides bacteroides caccae 8 0.25 32 bacteroidetes bacteroides bacteroides fragilis enterotoxigenic (et) 2 4 0.5 bacteroidetes bacteroides bacteroides fragilis nontoxigenic 1 0.25 4 bacteroidetes bacteroides bacteroides ovatus 0.5 0.5 1 bacteroidetes bacteroides bacteroides thetaiotaomicron 0.25 0.125 2 bacteroidetes bacteroides bacteroides uniformis 2 0.5 4 bacteroidetes bacteroides bacteroides vulgatus 0.125 0.016 7.8 bacteroidetes bacteroides bacteroides xylanisolvens 1 0.25 4 bacteroidetes bacteroides bifidobacterium subtile biavati >8 8 not determined bacteroidetes odoribacter odoribacter splanchnicus 8 4 2 bacteroidetes parabacteroides parabacteroides distasonis 8 2 4 bacteroidetes parabacteroides parabacteroides merdae 0.06 0.016 3.8 firmicutes blautia blautia obeum 1 0.5 2 firmicutes clostridium clostridium bolteae 4 0.5 8 firmicutes clostridium clostridium ramosum 2 0.06 33.3 firmicutes clostridium clostridium saccharolyticum 2 2 1 firmicutes dorea dorea formicigenerans 0.25 0.06 4.2 firmicutes eubacterium eubacterium eligens >8 4 not determined firmicutes lactobacillus lactobacillus paracasei 1 0.25 4 proteobacteria escherichia escherichia coli iai1 16 8 2 sac fungi candida candida albicans 32 16 2 sac fungi candida candida glabrata 32 32 1 sac fungi candida candida parapsilosis 32 16 2 sac fungi candida candida tropicalis 16 16 1 skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 283 covid concept maskne: a potential misnomer? muneeb ilyas do1, william hund do1, gabriella vasile do1, eduardo weiss, md2 1department of dermatology, larkin community hospital, palm springs campus 2department of dermatology and dermatologic surgery, miller school of medicine at university of miami the sars-cov-2 (covid-19) pandemic has led to the global adoption of mask wearing among laypersons and health care professionals alike. in order to contain the spread of covid-19, facial masks must be tightly adhered to the skin, thus allowing for protection from airborne droplet transmission. certain occupational groups must wear masks for prolonged periods, particularly, health care providers. given the global increase in facial mask use, there has been a number of mask-related dermatologic pathologies that have been described in the recent literature1-5. the all-encompassing term “maskne (mask-related acne)” is gaining popularity among both healthcare providers and the general public. although there is certainly an increase in acne and acneiform lesions associated with prolonged facial mask use2,3,5, “maskne” may be a misnomer, causing non-dermatologic providers to misdiagnose patients with acne vulgaris, disregarding several other differential diagnoses such as perioral dermatitis, rosacea, seborrheic dermatitis, folliculitis, irritant or allergic contact dermatitis, and acne mechanica. there are several reasons why facial mask use leads to skin pathology. these include, for example, changes in the skin microbiota, increased temperature and humidity, prolonged pressure, and shearing forces associated with the tight seal of a facial mask. each of these can induce skin injury and subsequent pathology2. there are reports of acne vulgaris, contact dermatitis, acne mechanica, facial ulcers, itching, and generalized rashes associated with prolonged mask use13,5,6. although these pathologies are certainly evident and seem to be exacerbated by prolonged mask use, the dermatologic literature lacks reports on the increasing incidence of various other cutaneous pathologies associated with wearing facial masks. in our recent experience, we are seeing more patients with cutaneous features consistent with perioral dermatitis, including monomorphic red papules in the perioral region, often sparing the skin adjacent to the vermillion border. abstract the covid-19 pandemic has led to the global adoption of mask wearing to contain the rampant spread of the virus. certain occupational groups, particularly health care providers, must wear masks for prolonged periods. alongside this pandemic emerged the use of the all-encompassing term “maskne”, used to describe mask-related dermatologic pathologies. although there is an increase in acne and acneiform lesions associated with prolonged facial mask use, “maskne” may be a misnomer, causing non-dermatologic providers to misdiagnose patients with acne when they, in fact, have an alternate cutaneous pathology. skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 284 these findings are not limited to health care workers using n95 masks (figure 1a); but, they are also evident among laypersons using cloth or paper-based facial masks (figure 1b). perioral dermatitis does not have a clear etiology and is thought to be caused by excessive topical steroid use or withdrawal, inhaled corticosteroids, infection, fluorinated toothpaste, cosmetic products, and hormonal imbalances7. it is proposed that environmental factors lead to perifollicular and perivascular inflammation that subsequently causes erythematous-grouped papules around the mouth, eyes, and nose. when considering diagnosing patients presenting with “maskne”, it is important to consider the broad differential diagnoses of “maskne” (table 1). we have found that a significant number of patients who were referred to our clinic complaining of “maskne” often lack the classic comedones of acne and instead have clinical findings associated with perioral dermatitis or a broad array of differential diagnoses. pruritus and skin sensitivity are common associated findings. these patients lack the scaling plaques distributed in the nasolabial folds as seen in seborrheic dermatitis. further, they lack the background erythema and centrofacial distribution of papulopustules associated with rosacea. although there is certainly an increase of numerous mask-related pathologies, it is unclear why there appears to be an increase in patients with clinical features more consistent with perioral dermatitis than other mask-related skin problems; thus, necessitating the need for further investigation. first-line treatments of perioral dermatitis include topical antibiotics, topical calcineurin inhibitors, and topical sulfur preparations. other treatments include oral tetracyclines in adults and erythromycin in children and pregnant or nursing females. given that multiple “maskne”associated conditions currently described such as acne vulgaris, rosacea, and folliculitis often share similar treatments, patients generally show improvement of their symptoms with topical or oral antibiotics. treatment regimens for other mask-related cutaneous pathologies are discussed in table 1. we see marked improvement in our patient’s symptoms with short courses of oral doxycycline. importantly, oral and topical antibiotics would not be expected to improve the symptoms of other “maskne”-associated conditions such as irritant/allergic contact dermatitis, acne mechanica, and seborrheic dermatitis. further, unlike in acne vulgaris, topical retinoids are not considered to be a mainstay in treating periorificial dermatitis8. we have seen evidence of retinoid-induced exacerbations of pod, particularly at the onset of treatment. this could be unfavorable for patients presenting with “maskne” who are then prescribed topical retinoids, only worsening their condition. the use of the term “maskne” is seemingly problematic as it is misleading for both patients and nondermatologic health care providers. additionally, there is an increased psychological burden on patients being told they are treated for “maskne”, especially those with no prior history of acne. the covid-19 pandemic and the associated personal protective equipment are to be a part of our daily lives for the foreseeable future. the incidence of mask-related dermatologic conditions will surely increase so it is imperative that the nomenclature be appropriately adjusted as to not mislead health-care providers and the community at large. the differential of mask-induced dermatitis can include perioral dermatitis, acne vulgaris, acne mechanica, rosacea, allergic contact dermatitis, seborrheic dermatitis, irritant dermatitis, and folliculitis. it is imperative that health care providers are skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 285 able to confidently diagnose and treat the associated condition optimally. conflict of interest disclosures: none funding: none corresponding author: muneeb ilyas, do department of dermatology larkin palm springs campus phone: 602-327-5087 email: muneebilyas1@gmail.com references: 1. szepietowski jc, matusiak ł, szepietowska m, et al. face mask-induced itch: a self-questionnaire study of 2,315 responders during the covid-19 pandemic. acta derm venereol. 2020 may 28;100(10):adv00152. 2. aguilera sb, de la pena i, viera m, et al. the impact of covid-19 on the faces of frontline healthcare workers. j drugs dermatol. 2020 sep 1;19(9):858-864. 3. han c, shi j, chen y, zhang z. increased flare of acne caused by long-time mask wearing during covid-19 pandemic among general population. dermatol ther. 2020 may 29:e13704. 4. long h, zhao h, chen a, et al. protecting medical staff from skin injury/disease caused by personal protective equipment during epidemic period of covid-19: experience from china. j eur acad dermatol venereol. 2020 may;34(5):919-921. 5. giacalone s, minuti a, spigariolo cb, et al. facial dermatoses in the general population due to wearing of personal protective masks during the covid-19 pandemic: first observations after lockdown. clin exp dermatol. 2020 jul 13:10.1111/ced.14376. 6. foo cc, goon at, leow yh, et al. adverse skin reactions to personal protective equipment against severe acute respiratory syndrome--a descriptive study in singapore. contact dermatitis. 2006 nov;55(5):291-4. 7. tolaymat l, hall mr. perioral dermatitis. 2020 sep 12. in: statpearls [internet]. treasure island (fl): statpearls publishing; 2020 jan–. pmid: 30247843. 8. ollech a, yousif r, kruse l, wagner a, kennerbell b, chamlin s, yun d, shen l, vivar k, reynolds m, paller as, mancini aj. topical calcineurin inhibitors for pediatric periorificial dermatitis. j am acad dermatol. 2020 jun;82(6):1409-1414. skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 664 brief article rare mucosal lip atypical fibroxanthoma treated with mohs micrographic surgery tara howard, bs1, taraneh matin, do2, john howard, do3, weiss eduardo, md4 1 nova southeastern university-kpcom, fort lauderdale, fl 2 larkin community hospital palm springs campus, dermatology, hialeah, fl 3 hollywood dermatology & cosmetics specialists, hollywood, fl 4 hollywood dermatology & cosmetics specialists, hollywood, fl atypical fibroxanthoma (afx) is a rare (0.002% of all non-melanoma skin cancers) cutaneous neoplasm of fibrohistiocytic mesenchymal origin and low-intermediate malignant potential. recurrence and local invasion may occur; however, the clinical outlook is excellent as metastatic potential is rare (0.5%). afx presents as a rapidly growing, solitary, red-pink, firm nodule with a mean diameter less than 2 cm and occasionally may ulcerate or bleed. these tumors present almost exclusively in the non-mucosal regions of the head and neck in light-skinned elderly males who have a history of significant sun exposure. ultraviolet (uv) radiation exposure leading to p53 mutations and cyclobutene pyrimidine dimers is the primary risk factor for development of afx. these tumors possess a predilection for sun-exposed areas in individuals with actinically damaged skin or previously treated skin cancer. further evidence supporting uv-induced pathogenesis is the higher incidence of afx in patients with xeroderma pigmentosum (xp), a disease characterized by mutated dna repair mechanisms. other, less common risk factors include prior radiation, burns, trauma or immunosuppression. we report a 73-year-old female with a lower lip mucosal afx. a literature search of lower lip afx revealed only one case of malignant afx on the lower lip of an elderly male and one on the lower lip in a male pediatric patient with a history of xp. the location of afx on the lower mucosal lip makes this case notably rare. abstract atypical fibroxanthoma (afx) is a rare dermal neoplasm of low-intermediate malignant potential found almost exclusively in the non-mucosal regions of the head and neck in light-skinned elderly males who have a history of significant sun exposure. due to its risk of misdiagnosis of more common skin lesions and possibility of metastases, afx requires resection with either mohs micrographic surgery (mms) or wide local excision (wle). the purpose of this brief article is to discuss the best comprehensive treatment for a lower lip afx using mms versus wle. introduction case report skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 665 a 73-year-old female with a history of significant sun damage and non-melanocytic skin cancer presented to the clinic with the complaint of an enlarging lower lip lesion that did not improve with the use of otc products. examination revealed a 1.6 x 1.6 cm pink indurated nodule on the right medial, inferior vermilion of the labial mucosa (figure 1). the patient underwent a shave biopsy which revealed an atypical spindle cell tumor positive for cd10 and sma. desmin, s100, ck-aea/ae3, ber-ep4 and p63 were negative. a final diagnosis of afx was made. figure 1. the patient was treated in 2 stages of mohs micrographic surgery [mms] with a surgical margin of 0.2 cm. postoperative dimensions measured approximately 2 x 2 cm (figure 2). a mucosal advancement flap was used to repair the defect (figures 3). at one-week follow-up the surgical site revealed a wellhealed, linear scar absent of drainage or dehiscence and sutures were removed (figure 4). figure 2. figure 3. afx requires aggressive treatment due to its risk of misdiagnosis and possibility of metastases. patients treated with mms have a recurrence rate of 2-4.6%, often within 1-3 years of resection. a retrospective study compared 91 afx patients treated with either mms or wle [wide local excision] to determine which modality provided the best comprehensive treatment; of the 59 patients treated with mms, recurrence did not occur, whereas the 23 patients treated with wle had a recurrence rate of 8.7%. the median margin for mms clearance was found to be significantly smaller [0.4 cm] in comparison to 2 cm for a discussion skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 666 figure 4. wle clearance of 95%. therefore, mms with complete resection is preferred over wle because the recurrence rate is reduced, the incidence of metastases is lowered and more facial tissue is preserved providing the greatest aesthetic outcome1,2. to maintain normal anatomy, optimal function, and cosmetic integrity of the inferior vermilion labial mucosa, we considered mucosal advancement flap as the most ideal repair technique. our patient responded well to both mms and mucosal advancement flap repair; not only was her neoplasm effectively removed and treated, the choice in repair provided for a smooth recovery and superior aesthetic results compared to alternative techniques. isolated afx on the lower lip mucosa is exceedingly rare as there has been only one case report in 1975. patients with a history of afx should undergo bi-annual skin examinations for signs of recurrence or presence of new skin malignancies, as these patients represent a high-risk group for development of uv associated malignancies. conflict of interest disclosures: none funding: none corresponding author: howard, tara, bs 3850 hollywood blvd #301 hollywood, fl 33021 email: th1302@mynsu.nova.edu references: 1. polcz, m.m., sebaratnam, d.f., & fernándezpeñas, p. atypical fibroxanthoma management: recurrence, metastasis and disease-specific death. the australasian journal of dermatology, 2018; 59(1), 10-25. 2. iorizzo, l.j., & brown, m.d. atypical fibroxanthoma: a review of the literature. dermatologic surgery: official publication for american society for dermatologic surgery, 2011; 37(2), 146-57. conclusion skin november 2017 volume 1 issue 3 copyright 2017 the national society for cutaneous medicine 156 brief articles clinical characteristics of patients diagnosed with strongyloidiasis in an urban outpatient dermatology department: a case series jacqueline watchmaker md a , sean legler bs b , dianne de leon md c , vanessa pascoe md d , robert stavert md mba c a boston university department of dermatology, 609 albany street, boston, ma 02118 b harvard medical school, 25 shattuck st, boston, ma 02115 c cambridge health alliance, 230 highland ave, somerville, ma 02143 d university of washington school of medicine, 1959 ne pacific st, seattle, wa 98195 key points:  chronic strongyloidiasis can be encountered in non-endemic areas and clinical manifestations are variable  eosinophilia was not a reliable indicator of chronic infection in this case series  dermatologists should consider serologic testing for strongyloidiasis in patients with a history of exposure and unexplained pruritus abstract background: although considered a tropical disease, strongyloidiasis may be encountered in non-endemic regions, primarily amongst immigrants and travelers from endemic areas. chronic strongyloides infection may be under-detected due to its non-specific cutaneous presentation and the low sensitivity of commonly used screening tools. methods: 18 consecutive patients with serologic evidence of strongyloides infestation who presented to a single urban, academic dermatology clinic between september 2013 and october 2016 were retrospectively included. patient age, sex, country of origin, strongyloides serology titer, absolute eosinophil count, presenting cutaneous manifestations, and patient reported subjective outcome of pruritus after treatment were obtained via chart review. results: of the 18 patients, all had non-specific pruritic dermatoses, 36% had documented eosinophila and none were originally from the united states. a majority reported subjective improvement in their symptoms after treatment for strongyloidiasis. conclusion: serologic testing for strongyloidiasis should be considered in patients living in non-endemic regions presenting with pruritic dermatoses and with a history of exposure to an endemic area. skin november 2017 volume 1 issue 3 copyright 2017 the national society for cutaneous medicine 157 strongyloides stercoralis (s. stercoralis) is a helminthic parasite that infects an estimated 30-100 million people worldwide. 1 infection with strongyloides, or strongyloidiasis, is endemic to several regions of the world and parts of southeastern united states. 2,3 global surveillance has found rising prevalence of strongyloidiasis in many regions of the world 2 as well as underreporting of prevalence in several countries. 4 in non-endemic regions of the world, strongyloidiasis has been described primarily in immigrants and travelers from endemic countries. 5 the clinical and laboratory manifestations of strongyloidiasis can vary greatly amongst patients depending upon host factors and the chronicity of infection. acute infection most commonly manifests with pulmonary or gastrointestinal symptoms, while chronic infection may produce variable cutaneous manifestations. 6,7,8 identification and diagnosis of chronic strongyloidiasis can be challenging due to the wide range of clinical manifestations and lack of sensitivity and specificity of traditional methods of detection. we report clinical and laboratory findings of 18 patients with serologic evidence of strongyloidiasis presenting over a 3-year period to a single urban, academic dermatology clinic in the northeastern united states. after institutional review board (irb) exemption and ethical approval was granted by the cambridge health alliance irb committee, 18 consecutive patients with serologic evidence of strongyloides infestation who presented to a single urban, academic dermatology clinic between september 2013 and october 2016 were retrospectively included in this case series. all patients denied previous treatment for strongyloidiasis. patient age, sex, country of origin, serology titer, absolute eosinophil count, and presenting cutaneous manifestations were obtained via chart review. strongyloides antibodies were detected by enzyme-linked immunosorbent assays (elisa) on microtitration wells sensitized with strongyloides ratti (s. ratti) antigens. patients were treated with ivermectin 0.2mg/kg in a single dose for 2 days after other common causes of pruritus were ruled out. none of the patients reported prior anti-helminthic therapy. at follow-up (average follow-up time 5.5 months, range 1 to 15 months), patients were evaluated for subjective change in their pruritus. among 18 patients, 8 (44.4%) were female and 10 (55.6%) were male with a mean age of 47.1 years (range 28-62). eosinophil count was checked in 14 (77.7%) patients prior to treatment. of these 14 patients, five (35.7%) had eosinophilia (defined as >500 eosinophils per microliter). average strongyloides titer prior to treatment was 21.3 (range 10.1 to 60.8). five patients had serology titers drawn after treatment with ivermectin. the average decrease in titer was 11.7 (range 5.0 27.7). none of the patients in this case series were originally from the united states. countries of origin included brazil (10/18), el salvador (3/18), pakistan (1/18), portugal (1/18), background methods results skin november 2017 volume 1 issue 3 copyright 2017 the national society for cutaneous medicine 158 nepal (1/18), haiti (1/18) and bangladesh (1/18). patients presented with a variety of nonspecific pruritic dermatoses and cutaneous manifestations of chronic pruritus, including lichen simplex chronicus (lsc) eczematous dermatitis, prurigo nodularis, postinflammatory hyperpigmentation (pih), dermatographism, lichen amyloid, and macular amyloid. no patient had evidence of the pathognomonic larva currens. after treatment with ivermectin, 7 (38.9%) patients reported improvement of pruritus, 6 (33.3%) had complete resolution of pruritus, and 2 (11.1%) had persistent pruritus with no improvement. 3 (16.7%) patients were lost to follow-up (table 1). one brazilian patient in our series was diagnosed with bullous pemphigoid by direct immunofluorescence and serology and was subsequently found to have a strongyloidiasis on serology. this patient was treated with ivermectin prior to initiating immunosuppressive therapy. table 1: study population age, eosinophil count prior to treatment, cutaneous manifestations at presentation, country of origin and patient reported pruritus after treatment. x indicates data was not collected. age (years) eosinophils (cells/microl) cutaneous manifestations at presentation country of origin pruritus at follow-up 62 171.1 lichen simplex chronicus pakistan lost to follow-up 55 x lichen simplex chronicus el salvador improved 54 1306.4 eczematous dermatitis portugal improved 50 198 prurigo nodulairs hati resolved 51 x eczematous dermatitis brazil improved 28 421.8 pruritus, alopecia areata brazil resolved 55 x pruritus, no rash brazil resolved 30 962.8 pruritus, bullae brazil persisted 49 61.8 eczematous dermatitis el salvador lost to follow-up 54 2688.3 eczematous dermatitis brazil improved 44 199.8 papular dermatitis brazil resolved 52 x eczematous papular dermatitis brazil improved 55 1323 post inflammatory hyperpigmentation, pruritus nepal lost to follow-up 38 136 pruritus, dermatographism el salvador resolved 35 777 pruritus, dermatitis brazil persisted 49 279 pruritus, dermatographism bangladesh improved 45 79.3 macular amyloid brazil resolved 42 172.2 lichen amyloid brazil improved skin november 2017 volume 1 issue 3 copyright 2017 the national society for cutaneous medicine 159 strongyloidiasis can reside in a host for decades without detection or treatment. 10 although often considered a tropical disease, strongyloidiasis may be diagnosed in individuals who emigrate or travel from endemic to non-endemic areas who harbor this infection from a past exposure. in our case series, 18 patients with serologies suggestive of strongyloidiasis were identified in a single urban, academic dermatology clinic in somerville, massachusetts over a 3year period. a recent study from the gastronenterology division of the same hospital identified 40 patients with strongyloidiasis over a four-year period. 11 physicians should be particularly diligent to consider strongyloides in patients with a history of exposure to an endemic area prior to initiating immunosuppressive therapy, as strongyloides can cause a hyperinfection syndrome with severe disseminated disease in immunocompromised patients. in our case series, one patient was diagnosed with bullous pemphigoid and strongyloides infection and therefore was treated with ivermectin prior to initiating immunosuppressive therapy. although the presence of eosinophilia may raise suspicion for a parasitic infestation, eosinophilia is not always present and decreases with the chronicity of the infection. 12 prior studies demonstrate a wide range (21.1 to 82.6%) in the percentage of patients with strongyloidiasis who had eosinophilia. 10-11 in our study 34.7% had eosinophilia. although serial stool examination is commonly used for the diagnosis of strongyloides, this test is laborious, technically demanding, and practically burdensome to patients. it has been shown that a single stool examination fails to detect larvae in up to 70% of cases, and 3 stool examinations only increases sensitivity to 50%. 9 serologic studies for strongyloides infestation are a clinically useful alternative. the serologic test used in our institution has a sensitivity of 88% and specificity of 94% and has a raw cost equivalent to a single stool examination ($6.00usd). additionally, there is typically a significant drop in titer by 6 months after parasite eradication and thus serology can be used as a “test of cure”. in our case series, the average drop in titer was 11.7 (range 5.0-27.7). serologic studies for strongyloides are limited by cross reactivity to other parasitic infections and an inability to distinguish between past and current infections. although causality between patients’ serologies for strongyloides and their cutaneous manifestations cannot be definitively linked, the anecdotal resolution of pruritus in several patients who had reported years of symptoms suggests that in at least some patients their pruritus may have correlated with chronic infestation. although considered a tropical disease, strongyloidiasis may be encountered in nonendemic regions among patients who have travelled or emigrated from endemic areas. this infection may be under-detected due to its non-specific cutaneous presentation and low sensitivity of commonly used screening tools. we hope dermatologists will consider serologic testing for strongyloides in patients discussion conclusion skin november 2017 volume 1 issue 3 copyright 2017 the national society for cutaneous medicine 160 from endemic regions with unexplained pruritus. conflict of interest disclosures: none. funding: none. corresponding author: jacqueline watchmaker 4 emerson place boston, ma 02114 phone: (262) 241-9224 email: jacqueline.watchmaker@gmail.com references: 1. bethony j, brooker s, albonico m, geiger sm, loukas a, et al. soil transmitted helminth infections: ascariasis, trichuriasis, and hookworm. lancet. 2006;367:15211532. 2. puthiyakunnon s, boddu s, li y, et al. strongyloidiasis-an insight into its global prevalence and management. plos negl trop dis. 2014;8:3018. 3. genta rm. global prevalence of strongyloidiasis: critical review with epidemiologic insights into the prevents of disseminated disease. rev infect dis. 1989;11:755-767. 4. montes m, sawhney c, barros n. strongyloides stercoralis: there but not seen. curr opin infect dis. 2010;23:500-504. 5. einsiedel l, spelman d. strongyloides stercoralis: risks posed to immigrant patients in an australian tertiary referral centre. intern med j. 2006 oct;36:632-7. 6. grove d. human strongyloidiasis. adv parasitol. 1996;38:251-309. 7. demessias it, telles fq, boaretti ac, et al: clinical, immunological and epidemiological aspects of strongyloidiasis in an endemic area of brazil . allergol immunopathol. 1987;15:37-41. 8. corsini ac. strongyloidiasis and chronic urticarial. postgrad med j. 1982;58:247-248. 9. nielsen pb, mojon m. improved diagnosis of strongyloides stercoralis by seven consecutive stool specimens. sentralbl bakeriol mikrobiol hyg. 1987;263:616-618. 10. loutfy m, wilson m, keystone j, kain k. serology and eosinophil count in the diagnosis and management of strongyloidiasis in a non-endemic area. am j trop med hyg. 2002;66:749-752. 11. payne m, osgood r, brown a. an unexpected epidemic: schistosomiasis and strongyloides infections detected in an academic urban community gi practice. a case series of 104 patients. j gastroenterol hepatol. 2013;1:76-86. 12. grove di. strongyloidiais: a major roundworm infection of man. london, uk: taylor and francis; 1989. skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 101 original research assessment of the 31-gene expression profile test by dermatologists: a cross-sectional survey from national dermatology conferences justin w. marson, md1, graham h. litchman, do, ms2, ryan svoboda, md, ms3, alex glazer, md4, aaron s. farberg, md5, richard r. winkelmann, do6, darrell s. rigel, md, ms7, the skin cancer prevention working group 1national society for cutaneous medicine, new york, ny 2department of dermatology, st. john’s episcopal hospital, far rockaway, ny 3department of dermatology, penn state college of medicine, hershey, pa 4dermatology science and research foundation, buffalo grove, il 5section of dermatology, baylor university medical center, dallas, tx 6optumcare, los angeles, ca 7department of dermatology, nyu grossman school of medicine, new york, ny abstract background: the 31-gene expression profile (31-gep) test uses 31 genetic markers obtained from the initial biopsy of a melanoma to assess melanoma-specific survival and sentinel lymph node positivity. objective: to assess the professional understanding, opinions, and clinical usage of the 31-gep test by dermatologists. methods: data from 589 unique dermatologists were collected during 2 virtual, nation-wide dermatology conferences via an 18-question survey on practice demographics and their clinical use and opinion of the 31-gep test. results: participants reported that integrating the 31-gep test may benefit patients by increasing knowledge and understanding (72.5%), personalizing treatment options (58.8%), and easing uncertainty about the future (59.7%). benefits of using the 31-gep test included identifying true negative patients in high-risk populations (65.6%) as well as true positives in low-risk populations (70.6%).a majority of participants also noted that if a patient received a 31-gep class 2b result, they would escalate subsequent management even if the lesions were classified as t1 (61.4%) or ajcc8 stage i (59.0%). 84.9% of participants were somewhat to very likely to use 31-gep testing for patient management or recommend this test to a colleague. limitations: potential respondent-selection and recall bias. conclusion: dermatologists are increasingly integrating the 31-gep test into their melanoma clinical management decisions. as the 31-gep test becomes more prevalent in practice, patients may benefit from decreased anxiety and uncertainty from enhanced prognosis, decreased need for unwarranted procedures such as sentinel lymph node biopsy and optimized allocation of healthcare resources. skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 102 the 31-gene expression profile test (31gep) (decisiondx-melanoma, castle biosciences, inc., friendswood, tx) analyses tissue collected from the initial diagnostic biopsy of a melanoma with an array of 31 genetic markers to assess prognosis. prior studies have validated its ability to determine the risk of local/distant recurrence and sentinel lymph node positivity to assist in clinical decisionmaking.1-3 the 31-gep test is reimbursable under medicare, certified by the clinical laboratory improvement amendments (clia), and was ordered over 16,000 times during 2019.1,4 given the increasingly widespread use of 31-gep, the purpose of this study was to assess the professional understanding, opinions, and clinical usage of the 31-gep test by dermatologists. the survey was available electronically via a website link during 2 national dermatology conferences from october 29, 2020 to november 1, 2020 and january 16-24, 2021. participants were asked to complete an 18 question survey regarding practice demographics, factors considered prior to ordering 31-gep, their integration of 31gep results into clinical management, and their opinions on the usefulness of the test. irb approval was obtained. participants were compensated for their participation. any duplicates were removed prior to data analysis. after removing non-us respondents, 589 participants were eligible for the final table 1. participant demographics. a majority of participants were practicing dermatologists in a private practice setting with at least 11 years of independent practice experience. a majority of participants noted diagnosing <50 new melanomas in 2019 and ordering <20 31-gep tests over a 12 month period. demographics (n = 458) % (n) primary specialty dermatologist 89.5 (527) mohs surgeon 9.2 (54) dermatopathologist 1.4 (8) years of training resident 20.5 (121) 1-10 years 31.2 (184) 11-20 years 19.4 (114) 21-30 years 16.0 (94) >30 years 12.9 (76) practice type private practice 65.2 (384) academic 24.1 (142) multispecialty group 7.1 (42) dermatology group 1.4 (8) government 1.0 (6) other‡ 1.0 (6) how many newly diagnosed melanoma patients did you see in 2019? <20 47.5 (280) 20-50 41.1 (242) 51-100 8.7 (51) 101-200 1.9 (11) >200 0.8 (5) in the past 12 months, how many times have you ordered the castle 31gep test? 0 54.8 (323) 1-20 42.6 (251) 21-50 2.2 (13) 51-100 0.3 (2) ‡other practice types: unemployed (1), volunteer (1), locum tenens (1), retired (3) analysis. over 65% of the participants were private practice dermatologists with 48.2% having at least 11 years of independent clinical practice (table 1). 52.5% of participants diagnosed at least 20 new introduction methods results skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 103 melanomas in 2019 with 42.6% ordering between 1 and 20 31-gep tests within the past 12 months. a majority of participants reported that integrating the 31-gep test may benefit patients by increasing knowledge and understanding (69.9%), personalizing treatment options (57.9%), and easing uncertainty about the future (58.6%) (table 2). even for patients with the lowest risk of recurrence (i.e. class 1a), 65.9% of participants reported potential benefits for ameliorating patients’ anxiety and 45.8% reported increasing confidence in their management. of the participants that offer the 31-gep test to patients, 33.3% reported patients expressed no concerns with the test. if concerns were noted, the most common was the potential cost (30.9%). study participants reported that benefits of using the 31-gep test included identifying true negative patients in high-risk populations (65.9%) as well as true positives in low-risk populations (70.1%). additional benefits included using test results to determine referrals/follow-up frequency (36.3%) and informing discussion regarding potential sentinel lymph node biopsy (slnbx) (36.0%). a majority reported breslow thickness ≥ 0.8mm (68.6%) and patient age/sex/history (55.7%) were factored into their decision to order the test. a majority of participants also noted that if a patient received a 31-gep class 2b result (which has previously been found to carry increased risk for recurrence within 5 years1), they would escalate subsequent management even if the lesions were classified as t1 (61.0%) or ajcc8 stage i (58.7%). respondents believed potential false positive class 2b results (i.e. patients at high risk of recurrence within 5 years that do not develop recurrence/metastasis) may be due to prompt/early intervention (71.3%), surgical excision prior to metastatic event (66.0%), or host immune response (71.5%) with a minority (31.2%) believing the result was an intrinsic error with the 31-gep test. going forward, 84.9% of participants were somewhat to very likely to use 31-gep testing for patient management or recommend this test to a colleague and 66.0% would recommend a friend or family member receive the test as part of their care. our findings suggest that a majority of dermatologists not only positively view 31gep testing, but are also incorporating it into management of their melanoma patients. participants noted that having 31gep class results had psychosocial benefits by aiding the physician-patient counseling, reducing anxiety and increasing confidence in the care plan. given the test is reimbursable under medicare, this may also ameliorate some patient concerns regarding the potential cost of the test. from a clinical perspective, the way the studied dermatologists report using 31-gep testing largely follows published appropriateuse criteria for the 31-gep test.6 prior studies have determined the usage of the 31-gep test with the strongest support in the literature was in informing discussions regarding the need for slnbx (a-strength sort recommendation7) with additional recommendation for facilitating management decisions of t1 and t2 melanomas and length of follow-up,6 which is consistent with our results. participants also reported confidence in the test with a minority discussion skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 104 table 2. participant reponses to survey questions. survey question % (95% ci) what benefits do you think your patients gain from the castle 31-gep test results? (select all that apply) increased knowledge and understanding 69.9 (66.2-73.7) relief from uncertainty about future 58.6 (54.6 – 62.6) more personalized treatment options 57.9 (53.9 – 61.9) information relevant to life planning 43.6 (39.6 – 47.6) none 6.6 (4.6 – 8.6) most t1a patients (89.3%) will receive a low-risk gep score. do you think there’s value in a t1a patient receiving a low-risk class 1a result? (select all that apply) yes, it relieves uncertainty for patients. 65.9 (62.0 – 69.7) yes, it makes me more confident in my treatment plan. 45.8 (41.8 – 49.9) yes, other. 5.8 (3.9 – 7.7) no, there is no value. 16.0 (13.0 – 18.9) do patients ever express any concerns about having the castle 31-gep test performed or receiving the results of the test? (select all that apply) no 33.3 (29.5 – 37.1) yes-concerns about the accuracy of the test 11.4 (8.8 – 13.9) yes-concerns about the cost of test 30.9 (27.2 – 34.6) yes-concerns about the risks of test 2.9 (1.5 – 4.2) nai don’t offer the test to my patients 34.5 (30.6 – 38.3) for prognostic testing, which of the following provides a benefit for patient care? (select all that apply) identifying a true negative in a high-risk population 65.9 (62.0 – 69.7) identifying a true negative in a low-risk population 33.6 (29.8 – 37.4) identifying a true positive in a high-risk population 54.2 (50.1 – 58.2) identifying a true positive in a low-risk population 70.1 (66.4 – 73.8) none of the above 2.2 (1.0 – 3.4) how do you use castle 31-gep information? (select all that apply) as part of my decisions for follow-up schedules and referrals 36.3 (32.4 – 40.2) as part of my decision to recommend or not recommend a patient having an slnb 36.0 (32.1 – 39.9) to inform surveillance imaging 22.1 (18.7 – 25.4) to inform treatment decisions 24.8 (21.3 – 28.3) i don’t use the castle 31-gep 45.0 (41.0 – 49.0) which of the following factors would make you more likely to order the 31gep? (select all that apply.) breslow thickness ≥ 0.8mm 68.6 (64.8 – 72.3) presence of ulceration 44.7 (40.6 – 48.7) negative sentinel lymph node biopsy 28.0 (24.4 – 31.6) mitotic rate ≥2/mm2 45.8 (41.8 – 49.9) skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 105 none of the above 19.0 (15.8 – 22.2) which of the following factors do you also take into account when deciding to order the 31-gep? (select all that apply) patient age/sex/clinical history 55.7 (51.7 – 59.7) histological subtype 44.1 (40.1 – 48.2) location of tumor 34.3 (30.5 – 38.1) clark level 37.7 (33.8 – 41.6) none of the above 26.5 (22.9 – 30.0) t1 patients with a class 1a (lowest risk) castle 31-gep result have a five-year recurrence free survival rate (rfs) of 96.8%, compared to t1 patients with a class 2b (highest risk) result who have an rfs of 64.6%. would receiving a class 2b result for a t1 patient change your treatment plan? yes 61.0 (57.0 – 64.9) no 5.8 (3.9 – 7.7) i’m not sure 33.3 (29.5 – 37.1) stage i patients with a class 1a (lowest risk) castle 31-gep result have a fiveyear recurrence free survival rate (rfs) of 97.6%, compared to stage i patients with a class 2b (highest risk) result who have an rfs of 76.1%. would receiving a class 2b result for a stage i patient change your treatment plan? yes 58.7 (54.8 – 62.7) no 6.1 (4.2 – 8.0) i’m not sure 35.1 (31.3 – 39.0) a recently published meta-analysis of the performance of the 31-gep (greenhaw et al., jaad, 2020) demonstrates that patients with a class 2b result are 3 times more likely to have a metastatic event compared to patients with a class 1a result. however, not all class 2b patients will have a recurrence or metastatic event (false positive result). in your opinion, which of the following factors could contribute to the receipt of a high-risk gep result for a tumor that does not subsequently develop a recurrence or metastasis? (select all that apply.) surgical excision completed before metastasis of the cancer 66.6 (62.7 – 70.4) host immune system 71.5 (67.8 – 75.1) early intervention 71.3 (67.7 – 75.0) incorrect gep result 31.2 (27.5 – 35.0) other (please specify)† 1.9† (0.8 – 3.0) if a close friend or family member were diagnosed with cutaneous melanoma, would you recommend that they get additional prognostic testing (such as gene expression profiling or gep) to aid in their decision making and care? yes 66.0 (62.2 – 69.9) no 5.6 (3.7 – 7.5) i’m not sure 28.4 (24.7 – 32.0) skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 106 how likely are you to use the castle 31-gep test for the care of your patients or to recommend the use of the test to a colleague? very unlikely 4.4 (2.8 – 6.1) not likely 13.8 (11.0 – 16.5) somewhat likely 47.7 (43.7 – 51.7) very likely 34.1 (30.3 – 38.0) †insufficient follow-up time (1), possible sampling error from tissue biopsy (1), “something else” currently not understood (1), imperfect predictive value of gene profile (1) attributing potential false-positives to intrinsic test errors and nearly 90% positively viewing, using, or recommending the test. . limitations of this study include potential respondent-selection bias and the retrospective nature of the study. however, the method of questionnaire delivery (i.e. during a nation-wide virtual conference) potentially minimized regional bias and the studied sample population has a relatively uniform distribution of practice experience. dermatologists are increasingly integrating the 31-gep test into their melanoma clinical management decisions. as the 31-gep test becomes increasingly prevalent in practice, patients may benefit from decreased anxiety and uncertainty from enhanced prognosis, decreased need for potentially unnecessary procedures such as slnbx and optimized allocation of healthcare resources. future studies will be needed to determine the impact that the 31-gep test will have on dermatology practices and patient outcomes when fully integrated into current melanoma clinical management algorithms. conflict of interest disclosures: jwm, ghl, rs, ag have no relevant disclosures or conflicts of interest. asf and rrw serve as consultants for castle bioscience, inc. dsr serves as a consultant, advisory board member, and speaker for castle biosciences, inc. funding: this study was funded in part by an unrestricted educational grant from castle biosciences, inc. skin cancer prevention working group: the skin cancer prevention working group is a multi-center collaboration of experts dedicated to the prevention of skin cancer. the working group consists of clinical and research specialists that have spent years investigating and understanding the diagnosis and management of melanoma and nonmelanoma skin cancer. the mission of the working group is to cultivate and analyze evidence-based research to better understand skin cancer pathophysiology, treatment, and prevention in order to be leaders in skin health education. corresponding author: justin w. marson, md 35 e 35th st. #208 new york ny, 10016 email: justin.w.marson@gmail.com references: 1. vetto jt, hsueh ec, gastman br, et al. guidance of sentinel lymph node biopsy decisions in patients with t1-t2 melanoma using gene expression profiling. future oncol. 2019;15(11):1207-1217. https://www.futuremedicine.com/doi/10.2217/fon2018-0912 2. berman, b., ceilley, r., cockerell, c., ferris, l., high, w. a., lebwohl, m., nestor, m. s., rosen, t., litchman, g. h., prado, g., svoboda, r. m., & rigel, d. s. (2019). appropriate use criteria for the integration of diagnostic and prognostic gene expression profile assays into the management of cutaneous malignant melanoma: an expert panel consensus-based modified delphi process assessment. skin the journal conclusion mailto:justin.w.marson@gmail.com skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 107 of cutaneous medicine, 3(5), 291-306. https://doi.org/10.25251/skin.3.5.1 3. marks, e., caruso, h. g., kurley, s. j., ibad, s., plasseraud, k. m., monzon, f. a., & cockerell, c. j. (2019). establishing an evidence-based decision point for clinical use of the 31-gene expression profile test in cutaneous melanoma. skin the journal of cutaneous medicine, 3(4), 239-249. https://doi.org/10.25251/skin.3.4.2 4. rigel ds, ceilley ri, litchman gh, cockerell cj. gene expression profile testing in skin cancer prognosis: the data is clear – it’s time to get on board. skin the journal of cutaneous medicine. 2020;4 (4):304-308. https://jofskin.org/index.php/skin/article/view/937 5. greenhaw bn, covington kr, kurley sj, yeniay y, cao na, plasseraud km, cook rw, hsueh ec, gastman br, wei ml. molecular risk prediction in cutaneous melanoma: a metaanalysis of the 31-gene expression profile prognostic test in 1,479 patients. j am acad dermatol. 2020 sep;83(3):745-753. doi: 10.1016/j.jaad.2020.03.053. epub 2020 mar 27. pmid: 32229276. 6. berman, b., ceilley, r., cockerell, c., ferris, l., high, w. a., lebwohl, m., nestor, m. s., rosen, t., litchman, g. h., prado, g., svoboda, r. m., & rigel, d. s. (2019). appropriate use criteria for the integration of diagnostic and prognostic gene expression profile assays into the management of cutaneous malignant melanoma: an expert panel consensus-based modified delphi process assessment. skin the journal of cutaneous medicine, 3(5), 291-306. https://doi.org/10.25251/skin.3.5.1 7. ebell mh, siwek j, weiss bd, et al. strength of recommendation taxonomy (sort): a patient-centered approach to grading evidence in the medical literature. american family physician 2004;69:548-56. skin november 2017 volume 1 issue 3 copyright 2017 the national society for cutaneous medicine 112 featured article acute generalized exanthematous pustulosis in association with hydroxyzine and cetirizine ofir noah nevo pharmd a , lois la grenade md a , ida-lina diak pharmd a , robert l. levin md a a united states food and drug administration abstract purpose: to review the occurrence of acute generalized exanthematous pustulosis (agep) with exposure to hydroxyzine and its active metabolites, cetirizine, and levocetirizine. methods: the division of pharmacovigilance of the food and drug administration (fda) searched the fda adverse event reporting system (faers) and the medical literature for cases of agep reported in association with use of hydroxyzine, cetirizine, and levocetirizine. causality was assessed using a modified world health organization uppsala monitoring centre (who-umc) causality assessment tool. results: the fda identified 26 cases of agep reported in association with the use of hydroxyzine (n = 21), cetirizine (n = 5), and levocetirizine (n = 3) (three cases included more than one drug product). hydroxyzine causality was probable in five of the cases, and cetirizine causality was probable in two of the cases. all levocetirizine cases were assessed as unlikely. conclusions: our findings supported an association between hydroxyzine and cetirizine and agep. as a result, fda has required labeling changes for hydroxyzine products to inform clinicians to avoid using hydroxyzine, cetirizine, and levocetirizine in patients who have experienced agep or other hypersensitivity reactions to any one of the above agents due to the risk of cross-reactivity. skin november 2017 volume 1 issue 3 copyright 2017 the national society for cutaneous medicine 113 acute generalized exanthematous pustulosis (agep) is an acute febrile cutaneous eruption, characterized by numerous small, superficial, non-follicular sterile pustules, arising within large areas of edematous erythema. more than 90% of cases of agep are drug induced. 1 it is serious, though typically not life-threatening once the offending drug is identified and discontinued. if drug exposure persists, the clinical picture may evolve into a toxic epidermal necrolysis (ten)-like picture with the complications of ten (e.g., fluid loss, bacterial infections). hydroxyzine is an antihistamine approved in the united states for symptomatic relief of anxiety, management of allergic pruritus, and as a sedative when used as a premedication and following general anesthesia. hydroxyzine’s active metabolites, cetirizine and levocetirizine, are marketed as antihistamines in the united states. in this report, we describe our review of the occurrence of agep with hydroxyzine, cetirizine, and levocetirizine. the division of pharmacovigilance of the food and drug administration (fda) searched the fda adverse event reporting system (faers) and the medical literature for cases of agep reported in association with use of hydroxyzine, cetirizine, and levocetirizine. the faers database supports fda’s post-marketing safety surveillance program for drugs and therapeutic biologics. a it contains adverse a for additional information on faers: http://www.fda.gov/drugs/guidancecomplianceregul atoryinformation/surveillance/adversedrugeffects/de fault.htm event and medication error reports submitted to the fda from product manufacturers, consumers, and healthcare professionals. using a modified world health organization uppsala monitoring centre (who-umc) causality assessment tool b , causality was assessed as probable, possible, or unlikely based on the documented diagnosis of agep (as confirmed by histology or diagnosed by a dermatologist), time relationship to drug intake, response to drug withdrawal, and whether agep could be attributed to an underlying disease or other drugs. the fda identified 26 cases of agep reported in association with the use of hydroxyzine, cetirizine, and levocetirizine. six cases originated from the medical literature – five involving hydroxyzine and one involving cetirizine. 2-7 twenty-two of the 26 cases required hospitalization as a result of agep. in all 26 cases, patients recovered from agep after discontinuing the drug (“positive dechallenge”). in three cases, reoccurrence of agep was reported after re-exposure to the drug (“positive rechallenge”), all involving hydroxyzine. table 1 provides additional characteristics of the 26 cases. table 2 provides a summary of the causality assessment. b for additional information on the who-umc causality assessment tool: http://www.whoumc.org/media/2768/standardised-case-causalityassessment.pdf methods results introduction skin november 2017 volume 1 issue 3 copyright 2017 the national society for cutaneous medicine 114 table 1. selected characteristics of acute generalized exanthematous pustulosis cases reported in association with hydroxyzine, cetirizine, and levocetirizine received by the fda through march 30, 2016 (n=26) age, years mean = 52.1 median = 57.5 range = 11 to 93 sex female = 14 male = 12 time to onset of agep from initiation of drug product of interest, days (n = 25) mean = 3.2 median = 1 range = 0 to 13 no. (%) drug product reported* hydroxyzine only = 19 (73) cetirizine only = 3 (12) levocetirizine only = 1 (4) hydroxyzine + cetirizine* = 1 (4) cetirizine + levocetirizine* = 1 (4) hydroxyzine + levocetirizine* = 1 (4) * three cases reported more than one drug product of interest as a suspect or concomitant drug. agep = acute generalized exanthematous pustulosis. table 2. causality assessment for acute generalized exanthematous pustulosis cases reported with hydroxyzine, cetirizine, and levocetirizine, received by the fda through march 30, 2016 (n=26) drug product probable possible unlikely no. (%) hydroxyzine (n=21*) 5 (24) 8 (38) 8 (38) no. (%) cetirizine (n=5*) 2 (40) 2 (40) 1 (20) no. (%) levocetirizine (n=3*) 0 0 3 (100) * causality assessment was performed for each drug product reported in a case. three cases reported more than one drug product of interest per case, so the sum of causality assessments for individual drug products equals more than the total number of cases in the case series (29 vs. 26). skin november 2017 volume 1 issue 3 copyright 2017 the national society for cutaneous medicine 115 our findings support an association between hydroxyzine and cetirizine and agep. all cases reported a close temporal relationship (median 1 day after drug initiation), and positive dechallenges. three cases reported a positive rechallenge. we did not find evidence of a plausible association between levocetirizine and agep. hydroxyzine has been marketed since 1956, and cetirizine is a widely used antihistamine, so agep may be a rare adverse reaction to these drugs. however, a contributing factor to the few reports received by fda may include overlooking the diagnosis, as hydroxyzine and cetirizine are often used to treat allergic skin conditions, and a worsening of the rash may be attributed to the underlying condition. based on the data in this analysis, the prescribing information of hydroxyzine was revised with a precaution about the rare, but serious, consequences of agep, and instructs clinicians to discontinue treatment with hydroxyzine if patients develop signs or symptoms of agep. clinicians should avoid using hydroxyzine, cetirizine, and levocetirizine in patients who have experienced agep or other hypersensitivity reactions to any one of the above agents due to the risk of cross-reactivity. cetirizine is currently regulated as an over-the-counter (otc) product only, and the cetirizine otc drug facts label was deemed to contain sufficient allergy warnings. the levocetirizine prescribing information was updated with the addition of postmarketing reports of agep with cetirizine. c c for complete prescribing information: https://dailymed.nlm.nih.gov/dailymed/ acknowledgements: we thank michael blum, md, mph (fda), for his critical review of the manuscript, and edward staffa, bspharm (fda), for technical review of the manuscript. conflict of interest: none disclosures: ofir nevo, lois la grenade, ida-lina diak, and robert levin are employees of the us food and drug administration. the views expressed in this article are those of the authors and not necessarily those of the us food and drug administration or center for drug evaluation and research. funding: none. corresponding author: ofir noah nevo, pharmd 10903 new hampshire avenue bldg 22, rm 3437 silver spring, md 20993 240-402-5280 ofir.nevo@fda.hhs.gov references: 1. valeyrie-allanore l, sassolas b, roujeau jc. druginduced skin, nail, and hair disorders. drug saf. 2007; 30: 1011-1030. 2. badawi ah, tefft k, fraga gr, liu dy. cetirizine-induced acute generalized exanthematous pustulosis: a serious reaction to a commonly used drug. dermatol online j. 2014; 20(5): 22613. 3. belgodère x, wolkenstein p, pastor mj. [acute generalized exanthematous pustulosis induced by iopamidol]. ann dermatol venereol. 2004; 131(8-9): 8312. [article in french] 4. kumar sl, rai r. hydroxyzine-induced acute generalized exanthematous pustulosis: an uncommon side effect of a common drug. indian j dermatol. 2011; 56(4): 447-8. discussion skin november 2017 volume 1 issue 3 copyright 2017 the national society for cutaneous medicine 116 5. o'toole a, lacroix j, pratt m, beecker j. acute generalized exanthematous pustulosis associated with 2 common medications: hydroxyzine and benzocaine. j am acad dermatol. 2014; 71(4): e147-9. 6. tsai ys, tu me, wu yh, lin yc. hydroxyzine-induced acute generalized exanthematous pustulosis. br j dermatol. 2007; 157(6): 1296-7. 7. utida t, fujimura n, ito k, aihara m, ikezawa z. hydroxyzine pamoate induced acute generalized exanthematous pustulosis (agep) followed by psoriasis vulgaris. poster presented at: 4th international drug hypersensitivity meeting; april 22-25, 2010; rome, italy. http://www.eurannallergyimm.com/cont/journalsarticles/183/volume-international-drug-hypersensitivitymeeting-rome-490allasp1.pdf (accessed 28 december 2016). skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 132 rising derm stars® in-vitro evaluation of pre-injection aspiration as safety checkpoint for hyaluronic fillers aaron s. farberg, md1, richard l torbeck, md, ezra hazan, md, jordan v wang, md, mbe, hooman khorasani, md 1department of dermatology, icahn school of medicine at mount sinai, new york, ny background/objectives: in 2017, about 2.1 million procedures using hyaluronic acid (ha) fillers were performed in the united states. while complications are rare, knowledge regarding their prevention and management are crucial. intra-arterial injection can cause visual impairment and local skin damage, including necrosis. the use of pre-injection aspiration has become controversial regarding its usefulness as some clinicians believe aspiration of blood is not possible. however, no study on pre-injection aspiration has thoroughly examined physiochemical and rheological properties, which can help predict behavior of ha fillers. our study investigated the utility of pre-injection aspiration as a safety checkpoint for ha fillers. methods: an in-vitro model consisted of fresh whole blood collected in edta-coated vacutainers that were pressure equalized. syringes containing ha filler were inserted, and plungers were each pulled back at 0.2cc and 0.5cc volumes to mimic pre-injection aspiration. the plunger was held at this distance until flashback was visualized or until 30 seconds had passed. syringes of 10 commonly used ha fillers were evaluated: allergan (pringy, france) juvederm ultra plus xc, juvederm ultra xc, juvederm volbella, juvederm vollure, and juvederm voluma; galderma (uppsala, sweden) restylane defyne, restylane lyft, restylane refyne, and restlyane silk; and merz (raleigh, n.c.) belotero balance. product original syringes and their package provided needles were utilized. values for physiochemical and rheological properties at 0.1 hz were gathered. results: for the 10 ha fillers, the values for ha concentration, g’, g’’, and g* varied. using a multivariable regression model (r2=.8324; f=12.42; p<.0001), ha concentration (p=.0016) and g* (p=.0017) were shown to positively affect time to flash, while g’ (p=.0017) and g’’ (p=.0029) were shown to negatively affect time to flash. needle gauge (p=.1641) and pullback distance (p=.3263) did not show any significant effect in this model. however, when comparing pullback distance using a paired analysis for each ha filler, 0.5cc pullback distance had a significantly decreased mean time to flash than 0.2cc (8.86 vs 10.86; p=.0389). all ha fillers, except for restylane defyne, showed a decreased time to flash with 0.5cc vs 0.2cc pullback distance. a significantly greater decrease in time to flash between 0.5cc and 0.2cc pullback distance was associated with ha concentration >21mg/ml (4.5 vs 0.57; p=.0166), g’ <153pa (4.4 vs 0; p=.0024), and skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 133 g* <155pa (4.4 vs 0; p=.0024), while g’’ showed no significant difference. conclusion: pre-injection aspiration may have utility as a safety checkpoint for ha fillers. practitioners may have to adjust pullback distance of the plunger and waiting time to visualize the flashback based on physiochemical and rheological properties. objective to describe the relationship between disease severity (as measured by body surface area [bsa]%) on patient-reported outcomes among us psoriasis (pso) patients using the adelphi pso disease specific programme (dsp). methods this study is based on real world survey data obtained from us adult patients with a diagnosis of pso and their treating dermatologists. patients were invited to self-complete a form containing the euroqol 5 dimensions (eq-5d), work productivity activity impairment (wpai) and the dermatology life quality index (dlqi) questionnaires and questions regarding their level of satisfaction with current treatment. three groups of patients were identified based on physician reports of bsa% with pso achieved with treatment at the time of completing the survey; bsa 0-2%= mild, 3-10%= moderate, >10%= severe. several factors including demographics, dlqi, wpai and eq-5d were compared across these patient groups. patient groups were compared using analysis of variance and chi-square tests. kruskal-wallis, fisher’s exact and student’s t-test where used where appropriate. results ■ of the 261 patients included; 132 had mild disease, 98 had moderate disease and 31 had severe disease activity at the time of completing the survey. ■ all groups had a similar age [mean (m)±standard deviation (sd) for each]; mild 47.5±17.2, moderate 48.5±14.7, severe 49.0±16.4. ■ proportions of females was 50.8% [mild], 44.9% [moderate], 35.5% [severe]. ■ of the mild patients 47% were prescribed a biologic at the time of completing the survey vs. 42.9% of moderate patients, and 67.7% of severe patients. ■ at initiation of current biologic 89.3% of currently mild patients had a bsa% of moderate to severe ■ at time of completing the survey, duration on a biologic in weeks was [m±sd] mild; 72.3±66.2, moderate 48.4±52.3, severe 34.4±59.6 (table 1). table 1. patient demographics currently mild (n=132) currently moderate (n=98) currently severe (n=31) mean age (±sd) 47.5 (±17.2) 48.5 (±14.7) 49.0 (±16.4) patient sex (%) male 49.2 55.1 64.5 female 50.8 44.9 35.5 proportion of patients on biologics: n (%) 62 (47%) 42 (42.9%) 21 (67.7%) proportion patients moderate to severe bsa at initiation of biologic: n (%) 50 (89.3%) 42 (100%) 25 (100%) duration on biologic in weeks (±sd) 72.3 (±66.2) 48.4 (±52.3) 34.4 (±59.6) ■ patient-reported satisfaction with treatment was significantly higher for patients who achieved a bsa% consistent with mild disease after treatment 86.2% vs. both moderate disease 58.7% (p<0.001) and severe disease 37.0% (p<0.001) (figure 1). figure 1. patient recorded satisfaction with treatment 86.2%* 58.7% 37.0% 0.0% 10.0% 20.0% 30.0% 40.0% 50.0% 60.0% 70.0% 80.0% 90.0% 100.0% patient recorded satisfaction mild moderate severe *denotes statistical significance ■ mean eq-5d score was significantly greater for patients who achieved a bsa% consistent with mild disease after treatment 0.927 vs. both moderate disease 0.881 (p<0.013) and severe disease 0.748 (p<0.001) (figure 2). figure 2. eq-5d score mild moderate severe 0.927* 0.881 0.748 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 eq-5d score *denotes statistical significance ■ mean dlqi score was significantly better for patients who achieved a bsa% consistent with mild disease after treatment 2.76 vs. both moderate disease 6.14 (p<0.001) and severe disease 9.64 (p<0.001) (figure 3). figure 3. dlqi score mild moderate severe 2.76* 6.14 9.64 0 2 4 6 8 10 12 dlqi score *denotes statistical significance ■ work productivity loss was lower for patients who had a bsa% consistent with mild disease after treatment 6.6% vs both, moderate disease 14.9% (p<0.008) and severe disease 26.5% (p=0.001), with activity impairment lower for patients who had a bsa% consistent with mild disease after treatment 11.5% vs. both moderate disease 18.6% (p<0.013) and severe disease 31.4% (p<0.001). presenteeism was lower for patients who had a bsa% consistent with mild disease after treatment 5.6% vs. both moderate disease 14.3% (p<0.002) and severe disease 25.0% (p<0.001) (figure 4). figure 4. work productivity and activity impairment (patient reported) mild moderate severe 6.6%* 5.6%* 14.9% 18.6% 11.5%* 14.3% 26.5% 31.4% 25.0% 0.0% 5.0% 10.0% 15.0% 20.0% 25.0% 30.0% 35.0% work productivity loss activity impairment presenteeism *denotes statistical significance conclusions ■ patients with plaque pso who achieved a lower severity consistent with mild disease after treatment (as measured by bsa% affected), had higher levels of self-reported satisfaction with treatment, less productivity loss, and a better qol than patients with higher disease severity. ■ plaque pso patients who achieved a lower severity consistent with mild disease after treatment were also more likely to have a longer duration of biologic treatment, suggesting that biologics have a positive impact on real-world patient reported outcomes. references 1. kim j, krueger jg. the immunopathogenesis of psoriasis. dermatologic clinics. 2015;33(1):13-23. 2. di meglio p, villanova f, nestle fo. psoriasis. cold spring harbor perspectives in medicine. 2014;4(8). 3. parisi r, symmons dp, griffiths ce, ashcroft dm. global epidemiology of psoriasis: a systematic review of incidence and prevalence. the journal of investigative dermatology. 2013;133(2):377-385. this study was supported by janssen scientific affairs, llc assessing the relationship between disease severity and patient-reported outcomes in psoriasis patients in the us j. lucas,1 a. teeple,2 j. hetherington,1 e. muser2 1adelphi real world; 2janssen scientific affairs, llc skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 76 short communication herpes zoster in an immunocompetent young patient following mrna-1273 vaccine for covid-19 nanjiba nawaz, ba1, christen samaan, md2, alexandra flamm, md2 1 penn state hershey college of medicine, hershey, pa 2 penn state hershey department of dermatology, hershey, pa herpes zoster (hz) is characterized by intraepidermal vesicular eruption that occurs in a dermatomal distribution with a prodrome of pain and pruritis. it is caused by the reactivation of the varicella zoster virus (vzv) in individuals with a history of primary varicella infection. vzv remains dormant in the cranial or dorsal root ganglia and can reactivate in patients who are older, immunocompromised such as hiv or lymphoma patients, as well as in stressful situations. hz has also been reported in children and immunocompetent individuals after administration of some vaccines including the live-attenuated varicella and yellow fever vaccines.1,2 here, we present a case of hz infection in a young, immunocompetent female following administration of the mrna-1273 vaccine. a 29-year-old female health care worker presented to clinic with a painful rash on her back that started 2 days after receiving the 1st dose of the mrna-1273 vaccine for covid-19. she also reported subjective fevers, myalgias, and left upper quadrant pain. her past medical history was only relevant for childhood chicken pox. on exam, she had grouped vesicles on an erythematous base (figure 1) in the t5/t6 dermatome on figure 1 the left side of the body (figure 2). based on the clinical presentation of pain accompanied by dermatomal rash, a diagnosis of herpes zoster infection was made. she was started on a 7-day course of 1g valacyclovir q8h. after discussion with the infectious disease specialists, she received an additional 7-day course of valacyclovir starting 2 days prior to the 2nd vaccine dose. patient received the second vaccine dose with no complications. at the time of this patient’s presentation, there had been no reports of hz in association with the covid-19 mrna-1273 vaccine in immunocompetent young adults. most cases of hz reactivation following skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 77 figure 2 mrna covid-19 vaccines were seen in older patients.3 there are also reports of concomitant hz in covid-19 positive patients, both in older and younger patients.4 however, more recently there have been some reports of hz infection in young immunocompetent individuals after receiving the covid-19 bnt162b2 and mrna-1273 vaccines.5,6,7 a dermatology clinic in las vegas reported 20 cases of herpes zoster, some in relatively young patients with no existing comorbidities, following the covid19 mrna vaccines. 12 out of 20 cases were with the mrna-1273 1st dose.5 similarly, a registry-based study on the covid-19 mrna vaccines reported a high rate of cutaneous manifestations, and zoster was diagnosed in 5% of total patients after the first dose of the mrna-1273 vaccine.6 there have been two proposed mechanisms of vzv reactivation in covid-19 infected patients. the more common one involves persistent impaired immunity with infection and includes covid‐19 virus induced lymphopenia, and functional impairment of cd4+ t cells.3,4,7 the second mechanism is triggered by acute-illness related stress which creates an inflammatory response followed by molecular and immune cell dysfunction.8 both these processes dampen the immune system and create avenues for hz reactivation. similar to the mechanism of the infection itself, covid-19 vaccines may cause transient lymphopenia or enhance the hyper-inflammatory response and result in immune dysregulation, as shown in phase i/ii clinical trials of the bnt162b2 vaccine.9 there is limited information on the occurrence of hz associated with the covid-19 vaccines. our case and the reports mentioned above highlight that hz can be seen after covid-19 vaccination. vzv reactivation can be seen with the pfizer® and moderna® vaccine, so therefore a class effect could be considered, however it should also be noted that other vaccinations can cause vzv reactivation outside of the mrna vaccines. this warrants further exploration on the topic, including the need for any prophylactic treatment prior to any subsequent covid19 vaccination. conflict of interest disclosures: none funding: none corresponding author: nanjiba nawaz 176a university manor east hershey, pa 17033 email: nnawaz@pennstatehealth.psu.edu references: 1. guffey dj, koch sb, bomar l, huang ww. herpes zoster following varicella vaccination in children. cutis. 2017 mar 1;99(3):207-11. 2. bayas jm, gonzález‐álvarez r, guinovart c. herpes zoster after yellow fever vaccination. journal of travel medicine. 2007 jan 1;14(1):656. mailto:nnawaz@pennstatehealth.psu.edu skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 78 3. bostan e, yalici‐armagan b. herpes zoster following inactivated covid‐19 vaccine: a coexistence or coincidence? journal of cosmetic dermatology. 2021;20(6):1566-1567. pmid: 33638924. 4. tartari f, spadotto a, zengarini c, zanoni r, guglielmo a, adorno a, valzania c, pileri a. herpes zoster in covid‐19‐positive patients. international journal of dermatology. 2020; 59(8):1028-1029. pmid: 32530063 5. lee c, cotter d, basa j, greenberg hl. 20 post covid‐19 vaccine related shingles cases seen at the las vegas dermatology clinic and sent to us via social media. journal of cosmetic dermatology. 2021;20(7):1960-1964. pmid: 33991162 6. mcmahon de, amerson e, rosenbach m, lipoff jb, moustafa d, tyagi a, desai sr, french le, lim hw, thiers bh, hruza gj. cutaneous reactions reported after moderna and pfizer covid-19 vaccination: a registry-based study of 414 cases. journal of the american academy of dermatology. 2021;85(1):46-55. pmid: 33838206 7. rodríguez-jiménez p, chicharro p, cabrera lm, seguí m, morales-caballero á, llamas-velasco m, sánchez-pérez j. varicella-zoster virus reactivation after sars-cov-2 bnt162b2 mrna vaccination: report of 5 cases. jaad case reports. 2021; 12:58-9. pmid: 33937467 8. saati a, al-husayni f, malibari aa, bogari aa, alharbi m. herpes zoster co-infection in an immunocompetent patient with covid-19. cureus. 2020;12(7) :e8998. pmid: 32670724 9. mulligan, m.j., lyke, k.e., kitchin, n. et al. phase i/ii study of covid-19 rna vaccine bnt162b1 in adults. nature 2020; 586(7830):589-93. pmid 32785213 skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 431 brief articles drug induced autoimmunity related neutrophilic dermatosis by calcium channel blockers maulik m. dhandha, md1, markiza cooper, md2, m. yadira hurley, md3, sofia chaudhry, md3 1maine dartmouth family medicine residency, augusta, me 2mayo clinic, department of dermatology, jacksonville, fl 3saint louis university, departments of dermatology, saint louis mo autoimmunity related neutrophilic dermatosis (arnd) is a recently described clinical-histopathological entity. in the setting of an autoimmune connective tissue disease (aictd), these patients develop a nonbullous urticarial eruption that does not resolve within 72 hours. histology is characterized by an interstitial neutrophilic infiltrate with leukocytoclasia along with a variable degree of vacuolar interface dermatitis.1 the nomenclature of arnd encompasses multiple prior case reports and series that describe a similar condition by different terminology, including nonbullous neutrophilic dermatosis (nbnd), nonbullous sweet-like neutrophilic dermatosis, and nonbullous neutrophilic lupus erythematosus (nbnle). it has primarily been reported in the setting of lupus, but has also been associated with rheumatoid arthritis and dermatomyositis. 1-6 herein we report a unique case of arnd in a patient with systemic lupus erythematosus (sle), whose eruption appears to have been triggered by starting a calcium channel blocker (ccb), given that the patient subsequently flared on a different ccb. to introduction abstract autoimmunity related neutrophilic dermatoses (arnd) is a recently described entity characterized by urticarial papules and plaques with histology showing a neutrophilic perivascular and interstitial infiltrates with leukocytoclasis, along with variable vacuolar interface dermatitis. we report a 38 year old caucasian female with a ten year history of lupus who presented with pruritic urticarial papules and plaques on the face, trunk, upper extremities and thighs. the onset occurred 10 days after she started a calcium channel blocker (ccb), diltiazem. histopathology revealed scattered dyskeratotic keratinocytes, vacuolar interface dermatitis, and a sparse perivascular and interstitial mixed infiltrate of neutrophils within the dermis. there was focal leukocytoclasis, dermal edema, and rare eosinophils. the patient initially improved with prednisone taper, but flared again upon starting a different ccb, verapamil. exposure to certain medications such as ccb in the setting of autoimmune connective tissue disorder may be the inciting trigger for a neutrophilic dermatoses. future studies may provide further information on the pathogenesis of arnd and cutaneous drug eruption in the setting of sle. skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 432 the best of our knowledge, there have been no prior reports of drug induced arnd. our patient was a 38 year-old caucasian female who presented to dermatology with a three day history of pruritic pink edematous urticarial papules coalescing into plaques on her face, trunk, upper extremities and thighs (fig. 1 and 2). her mucous membranes were unremarkable, and she denied any joint pain/swelling, fevers and increased sun exposure. she had a history of class iv lupus nephritis diagnosed 10 years prior, but her lupus had since been well controlled on only hydroxychloroquine 200 mg twice a day. (she was off hydroxychloroquine for one month due to insurance issues, but it was restarted two days prior to the eruption.) her other medications included bupropion and diltiazem, the latter being started 10 days prior to her eruption. the clinical differential diagnosis of her eruption included a flare of her sle, autoimmunity related neutrophilic dermatosis, a class four drug hypersensitivity, and urticaria. she was started on systemic corticosteroids while awaiting biopsy results. diltiazem was discontinued since it was a possible culprit, while hydroxychloroquine was continued. her histology revealed scattered dyskeratotic keratinocytes and vacuolar interface dermatitis (figure 3). there was a sparse perivascular and interstitial mixed infiltrate composed predominantly of neutrophils within the dermis (figure 4). there was focal leukocytoclasis and associated dermal edema. there was no fibrinoid necrosis of the vessels. there were sparse eosinophils within the infiltrate (figure 5). the differential diagnoses for this histology included non-bullous neutrophilic lupus erythematosus, a neutrophilic dermatosis, and a drug eruption. given the neutrophilic infiltrate, she was started on dapsone as her systemic steroid was tapered. autoimmune work up revealed positive anti-histone (1.7), ana (speckled), and anti-dsdna (30) antibodies. her skin continued to clear as her steroid dose was slowly tapered. after she had been on 20mg of prednisone daily for five days, she had a sudden severe flare of her eruption. at this time we learned that another provider had restarted her on another calcium channel blocker, verapamil, prior to the flare. her prednisone dose was again increased to 60mg daily, and we had the new ccb changed to an ace-inhibitor. because of the flare, rheumatology also started her on mycophenolate mofetil as a steroid sparing agent. however, as her prednisone dose was again tapered off over 3 months, she did not experience a flare. dapsone was then stopped. mycophenolate mofetil was also slowly tapered over 8 months by rheumatology. patient has not had any flares since getting off the medications. figure 1. pruritic edematous urticarial papules coalesced into plaques on face, neck, chest and upper arms. case report skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 433 figure 2. pruritic edematous urticarial papules coalesced into plaques on the back. figure 3. vacuolar interface dermatitis with superficial perivascular and interstitial neutrophilic infiltrate (10x). figure 4. vacuolar interface dermatitis with superficial perivascular and interstitial neutrophilic infiltrate (40x). figure 5. sirius red staining showing rare eosinophils in the infiltrate (100x). skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 434 the patient’s eruption of urticarial papules and plaques in the setting of lupus, combined with a histology of a predominantly neutrophilic perivascular and interstitial infiltrates with leukocytoclasis and vacuolar interface dermatitis is most consistent with autoimmunity related neutrophilic dermatosis (arnd). however, unlike prior reports, our patient had a new preceding medication: a calcium channel blocker. her eruption had a sudden, severe flare when she was re-exposed to second calcium channel blocker. the acute onset of the eruption 10 days after the initial exposure to calcium channel blocker along with the severe flare after re-exposure with another ccb indicate that her eruption may have been drug induced. the sparse eosinophils within the biopsy may also indicate a drug hypersensitivity reaction. although the main other differential diagnosis was a flare of her lupus erythematosus, the fact that she flared with re-exposure to another ccb makes this less likely. our case demonstrates that the exposure to certain medications, such as ccbs, may be the inciting trigger for a neutrophilic dermatosis that present as arnd. however this effect may be restricted to nondihydropyridine ccbs, as this patient was only exposed to this class of ccbs. additional studies are needed to further understand the pathogenesis of arnd and cutaneous drug eruptions in the setting of autoimmune connective tissue diseases. conflict of interest disclosures: m. yadira hurley and maulik m. dhandha have participated in clinical trials in the past. funding: none corresponding author: maulik m. dhandha, md maine dartmouth family medicine residency dermatology #340 ballard center, 6 chestnut street, augusta, me email: maulikdhandha@gmail.com references: 1. saeb-lima m, charli-joseph y, et al. autoimmunity-related neutrophilic dermatosis: a newly described entity that is not exclusive of systemic lupus erythematosus. am j dermatopathol 2013;35(6):655-60. [pmid: 23518639] 2. hau e, vignon pennamen md, battistella m, et al. neutrophilic skin lesions in autoimmune connective tissue diseases: nine cases and a literature review. medicine (baltimore). 2014 dec;93(29):e346. [pmid: 25546688] 3. brinster nk, nunley j, pariser r, et al. nonbullous neutrophilic lupus erythematosus: a newly recognized variant of cutaneous lupus erythematosus. j am acad dermatol. 2012;66:92–97. [pmid: 22050914] 4. pavlidakey p, mills o, bradley s, et al. neutrophilic dermatosis revisited: an initial presentation of lupus? j am acad dermatol. 2012;67:e29–e35. [pmid: 21907449] 5. gleason bc, zembowicz a, granter sr. nonbullous neutrophilic dermatosis: an uncommon dermatologic manifestation in patients with lupus erythematosus. j cutan pathol. 2006;33:721– 725. [pmid: 17083690] 6. satter ek, high wa. non-bullous neutrophilic dermatosis within neonatal lupus erythematosus. j cutan pathol. 2007;34:958–960. [pmid: 18001424] discussion mailto:maulikdhandha@gmail.com microsoft word lp.doc skin july 2017 volume i issue i copyright 2017 the national society for cutaneous medicine 32 brief articles apremilast for lichen planopilaris and frontal fibrosing alopecia: a case series ali hadi mda, mark lebwohl mdb amedical student, new york university school of medicine, new york, ny 10016 bsol and clara kest professor and chair of the department of dermatology, icahn school of medicine at mount sinai, new york, ny 10029 abstract abstract importance: lichen planopilaris and frontal fibrosing alopecia are characterized by scarring alopecia associated with pruritus, inflammation, and pain of affected areas. there is a paucity of data on treatment options for these disorders. the available management options are associated with significant adverse effects and poor efficacy. objective: to explore apremilast as a treatment option for refractory lichen planopilaris and frontal fibrosing alopecia design: this is a retrospective case series analyzing the outcomes of four patients with refractory lichen planopilaris or frontal fibrosing alopecia treated with apremilast. setting: the patients were seen in the faculty practice of an academic institution in new york city. participants: four female patients with biopsy confirmed lichen planopilaris or frontal fibrosing alopecia refractory to currently used treatments observations: we report a case series of four patients with lichen planopilaris and frontal fibrosing alopecia who had failed multiple previous treatments, including intralesional steroids, anti-malarials, oral anti-inflammatory agents, minocycline, acitretin, mycophenolate mofetil, and laser treatment who responded to apremilast. while two of these patients discontinued the drug due to adverse effects such as gastrointestinal discomfort, clinical improvement was seen in every patient. conclusions: to date, this is the first report of the use of apremilast for lichen planopilaris or frontal fibrosing alopecia, indicating its possible use in patients refractory to other treatments. skin july 2017 volume i issue i copyright 2017 the national society for cutaneous medicine 33 lichen planopilaris (lpp) and frontal fibrosing alopecia (ffa) are inflammatory, follicular disorders, characterized by cicatricial alopecia with associated pain and pruritus of affected areas. the diagnosis is based on clinical history as well as histopathologic findings indicating inflammation of the infundibulum and isthmus of the hair follicle. it classically affects women more than men and can be challenging to treat. currently used treatments include intralesional steroids, methotrexate, mycophenolate, hydroxychloroquine, finasteride, dutasteride, doxycycline, and minocycline. however, no randomized, double-blind trials have been conducted evaluating any treatments for lpp or ffa. we report a case series of four patients with biopsy proven lpp or ffa that was refractory to other treatments and responded to apremilast. to our knowledge, this is the first report of apremilast being used for lpp or ffa. case 1: a 62 year-old white female presented with a 4-year history of a pruritic, scaly, erythematous eruption on her scalp with associated hair loss. physical examination revealed irregular patches of decreased hair density over the anterior crown with perifollicular erythema and scaling. a scalp biopsy revealed perifollicular fibrosis and interface dermatitis involving the follicular infundibulum and isthmus, confirming the diagnosis of lichen planopilaris. the patient had previously attempted numerous treatments with minimal clinical response, including methotrexate at a dose of 15 mg weekly, hydroxychloroquine, finasteride, intralesional triamcinolone 10 mg/cc injections, acitretin 20 mg daily, cyclosporine 225 mg daily, mycophenolate mofetil 500 mg three times daily, and excimer laser. the decision was made to initiate treatment with apremilast at a dose of 30 mg twice daily and discontinue all other medications. within 3 months, significant improvement was noted in the scalp inflammation and pruritus. case 2: a 75 year-old white female with a history of hypothyroidism and depression presented with a one year history of hair loss and pruritus of the scalp. physical examination revealed erythema and scaling of the right anterior scalp with patchy alopecia. a scalp biopsy was performed, which revealed rare diminutive hairs with condensation of elastic fibers around fibrous tracts, indicating a late stage scarring process. the patient had received intralesional triamcinolone injections and minocycline 100 mg twice daily for months with minimal effect. apremilast was initiated at a dose of 30 mg daily and titrated up to 30 mg twice daily. there was some improvement in the patient’s clinical symptoms; however, she began experiencing depressive symptoms, as well as gastrointestinal discomfort. the apremilast dose was decreased to 30 mg daily and eventually discontinued due to the aforementioned side effects. case 3: a 70 year-old female presented with a few months history of hair loss and a painful sensation of the scalp. examination revealed erythematous patches with scaling and decreased hair density of the frontal scalp. scalp biopsy revealed perifollicular fibrosis and dermatitis involving the infundibulum. the patient was initiated on intralesional triamcinolone injections, minocycline 100 mg daily, and hydroxychloroquine 200 mg daily. the patient’s condition was not significantly improving, and apremilast 30 mg twice daily was initiated. four months later, the patient’s dose was decreased to 30 mg daily and eventually discontinued due to gastrointestinal discomfort and diarrhea. however, her lichen planopilaris had shown improvement. introduction skin july 2017 volume i issue i copyright 2017 the national society for cutaneous medicine 34 case 4: a 28 year-old female presented with a few months of burning sensation of the scalp and associated scattered hair loss. examination revealed decreased hair density with hyperkeratosis and perifollicular erythematous papules of the anterior crown of the scalp and bilateral eyebrows. scalp biopsy revealed concentric fibrosis of the hair follicles with a lymphocytic infiltrate of the infundibulum. she initiated monthly injections of intralesional triamcinolone for 10 months with concomitant topical clobetasol solution daily with minimal response. she also attempted oral finasteride for 10 months without effect. apremilast was then initiated at figure 1a. a 62 year-old white female presented with a 4-year history of lpp prior to initiation of apremilast. note the arrows indicating perifollicular erythema. figure 1b. 15 months into treatment with apremilast. note the resolution of perifollicular erythema. a dose of 30 mg twice daily. the patient reported some mild gastrointestinal discomfort, but continued to take the medication and reports improvement in her symptoms. figure 2a. a 75 year-old white female with a 1 year history of lpp prior to initiation of apremilast. note the arrows illustrating perifollicular erythema. figure 2b. two months into apremilast treatment, note the resolution of perifollicular erythema. figures skin july 2017 volume i issue i copyright 2017 the national society for cutaneous medicine 35 lichen planopilaris is a form of lichen planus characterized by inflammation and scarring alopecia of the scalp. it is subdivided into three forms depending on the pattern of involvement, classic lichen planopilaris, frontal fibrosing alopecia, and graham-little piccardi-lasseur syndrome.1 frontal fibrosing alopecia presents with alopecia involving the frontotemporal scalp, eventually progressing to the parietal scalp and eyebrows as well. it is most commonly seen in post-menopausal women of caucasian descent.2 because of this, some have speculated that the pathophysiology is related to hormonal imbalances; however, no consistent patterns of hormonal abnormalities have been detected in affected patients.3 the pathogenesis of lpp is not well understood; however, the leading theory is an autoimmune destruction of the hair follicle focused on the infundibulum and the isthmus, leading to the death of follicular stem cells as they are located in this region.1 in addition to disfigurement, lpp is associated with significant pruritus, discomfort, and pain of affected areas. as a result, patients often seek treatment and symptomatic relief for this condition. currently used treatments include topical and intralesional steroids, systemic steroids, oral minocycline, mycophenolate mofetil, hydroxychloroquine, methotrexate, excimer laser, and cyclosporine.4 unfortunately, these modalities often do not result in satisfactory outcomes and are associated with significant adverse effects, such as skin atrophy, cushing’s syndrome, hepatoxicity, renal toxicity, and neutropenia.4 furthermore, there are no randomized clinical trials assessing treatment agents for either lpp or ffa. mesinkovska et al has illustrated oral pioglitazone, a peroxisome proliferator activated gamma (ppar-γ) agonist to be effective in treatment of lpp based on recent evidence implicating the dysfunction of pparγ in cicatrical alopecias.5,6 however, this has not been replicated elsewhere. apremilast, a phosphodiesterase type iv inhibitor, acts to reduce the production of cytokines such as tnf-α, interferon-γ, leukotriene b4, and interleukins 2, 5, 8, and 12.7 it has been used successfully in psoriasis, psoriatic arthritis, rheumatoid arthritis, and sarcoidosis, and shows promise for other conditions.7 paul et al carried out a pilot study showing that apremilast may be an effective agent for the treatment of lichen planus.8 the results showed that 8 of 10 patients with biopsy-proven lichen planus demonstrated a 2-grade or higher improvement in the physician global assesment following 12 weeks of therapy. given that lpp is a follicular variant of lichen planus, we used apremilast in our cohort of patients with lpp refractory to currently used treatment modalities. we found apremilast to be effective in treating these patients’ symptoms, with all of them showing signs of improvement. however, two of our patients experienced significant gastrointestinal discomfort and one reported depression, leading to discontinuation of the drug. it is worth noting that one of these patients carried a previous diagnosis of irritable bowel syndrome and the patient who reported depression had a previous diagnosis of mood disorder. furthermore, these events were noted to be less prominent once the dose was lowered to 30 mg daily. two patients reported significant clinical improvement within three months of initiation of apremilast, with no significant adverse events noted. because lpp is a condition that causes significant morbidity and is often refractory to available treatments, patients are in dire need of novel agents that can provide symptomatic relief. to our knowledge, this is the first report of the use of apremilast for lpp. our limitations include our small sample size and lack of use of a standardized measure of discussion skin july 2017 volume i issue i copyright 2017 the national society for cutaneous medicine 36 clinical improvement. furthermore, spontaneous clinical improvement is a possibility in our patients; however, a retrospective review of 46 patients with lichen planopilaris showed that over 80% of patients had active disease 3 months after starting treatment.9 our experience suggests that apremilast may be a useful agent in treating refractory lpp. larger randomized trials are needed to fully assess its efficacy and tolerability. conflict of interest disclosures: mark lebwohl is an employee of the mount sinai medical center, which receives research funds from abgenomics, amgen, anacor, boehringer ingleheim, celgene, ferndale, lilly, janssen biotech, kadmon, leo pharmaceuticals, medimmune, novartis, pfizer, sun pharmaceuticals, and valeant. ali hadi has no conflicts of interest to declare. funding: none. corresponding author: ali hadi 550 first avenue new york, ny 10016 email: alihadi91@gmail.com tel: 201-294-8824 references: 1. assouly p, reygagne p. lichen planopilaris: update on diagnosis and treatment. semin cutan med surg. 2009;28(1):3-10. 2. holmes s. frontal fibrosing alopecia. skin therapy lett. 2016;21(4):5-7. 3. vano-galvan s, molina-ruiz am, serrano falcon c, et al. frontal fibrosing alopecia: a multicenter review of 355 patients. j am acad dermatol. 2014;70(4):670-678. 4. alexis af bv. skin of color: a practical guide to dermatologic diagnosis and treatment. 1 ed: springer-verlag new york; 2013. 5. karnik p, tekeste z, mccormick ts, et al. hair follicle stem cell-specific ppargamma deletion causes scarring alopecia. j invest dermatol. 2009;129(5):1243-1257. 6. mesinkovska na, tellez a, dawes d, piliang m, bergfeld w. the use of oral pioglitazone in the treatment of lichen planopilaris. j am acad dermatol. 2015;72(2):355-356. 7. thaci d, kimball a, foley p, et al. apremilast, an oral phosphodiesterase 4 inhibitor, improves patient-reported outcomes in the treatment of moderate to severe psoriasis: results of two phase iii randomized, controlled trials. j eur acad dermatol venereol. 2016. 8. paul j, foss ce, hirano sa, cunningham td, pariser dm. an open-label pilot study of apremilast for the treatment of moderate to severe lichen planus: a case series. j am acad dermatol. 2013;68(2):255-261. 9. lyakhovitsky a, amichai b, sizopoulou c, barzilai a. a case series of 46 patients with lichen planopilaris: demographics, clinical evaluation, and treatment experience. j dermatolog treat. 2015 jun;26(3):275-9. gbr 830 induces progressive and sustained improvements in atopic dermatitis skin biomarkers and clinical parameters emma guttman -yassk y1; ana b. pavel1; yeriel estr ada1; lisa zhou1; yacine salhi2; girish gudi2; vinu ca3; julie macoin4; jonathan back4; gerhard wolff2 1icahn school of medicine at mount sinai, new york, ny, usa; 2glenmark pharmaceuticals inc ., usa; 3glenmark pharmaceuticals ltd., india; 4glenmark pharmaceuticals sa , switzerl and synopsis/objective ◾◾ gbr 830 is an investigational, first-in-class, humanized, monoclonal igg1 antibody specific for inhibiting ox40, a costimulatory receptor on activated t cells1 ◾◾ by blocking binding of ox40 to its ligand ox40l, gbr 830 reduces longevity and efficacy of effector and memory t cells1 ◾◾ ox40 inhibition is suggested to have a potential therapeutic role in t  cell-mediated diseases, including atopic dermatitis (ad), one of the most common inflammatory skin disorders that affects up to 10% of adults2 ◾◾ this phase 2a proof-of-concept study in patients with moderate-tosevere ad (nct02683928) was conducted to investigate the safety of gbr 830, evaluate its effects on ad biomarkers, and generate the first clinical evidence of its biological activity methods study design ◾◾ randomized, double-blind, placebo-controlled, repeated-dose study conducted in 17 north american centers ◾◾ three phases: screening (up to 30 days), treatment (day 1 [baseline] and 29), follow-up (through day 85) (figure 1) ◾◾ treatment: randomization 3:1 to gbr 830 or placebo; 2 repeated doses (each 10 mg/kg, administered intravenously) on days 1 and 29 ◾◾ skin punch biopsies: obtained from lesional skin on days 1, 29, and 71 figure 1. study design -30 -1 4 8day dosing skin biopsy 15 22 29 32 4336 5750 71 85 s cr e e n in g treatment (double-blind) follow-up 1 gbr 830 (10 mg/kg) placebo subjects ◾◾ key inclusion criteria: •◾ adult subjects (≥18 years) with moderate-to-severe ad for >1 year •◾ affected body surface area (bsa) ≥10% •◾ eczema area and severity index (easi) score ≥12 •◾ scoring of atopic dermatitis (scorad) ≥20 •◾ investigator’s global assessment (iga) score ≥3 (5-point scale) •◾ history of inadequate response to topical therapies ◾◾ key exclusion criteria: •◾ live vaccination within 12 weeks before randomization •◾ history of serious infection, including latent or active tuberculosis •◾ prior treatment with systemic corticosteroids, topical steroids, phototherapy, and/or biologics study endpoints ◾◾ co-primary: treatment-emergent adverse events (teaes; frequency, severity); change from baseline in epidermal hyperplasia and active ad mrna expression biomarker signatures measured from lesional skin biopsies ◾◾ key secondary: easi 50 response (≥50% improvement from baseline) on day 29 and day 71 statistical analyses ◾◾ intent-to-treat (itt) population: all subjects who were randomized and received ≥1 partial or full dose of study drug ◾◾ safety population: all subjects who took ≥1 partial or full dose of study drug ◾◾ biological activity set (bas): all itt subjects who had ≥1 post-baseline skin biopsy and received both doses of study drug ◾◾ easi 50 response was analyzed descriptively at day 29 and day 71 ◾◾ immunohistochemistry and rt-pcr data was log2-transformed prior to analysis using a linear mixed effect model with time, tissue, and treatment as fixed factors and a random intercept for each subject results subjects ◾◾ itt/safety population included 62 subjects: gbr 830, n=46; placebo, n=16 (figure 2) ◾◾ bas population included 40 subjects: gbr 830, n=29; placebo, n=11 figure 2. subject disposition screened (n=100) randomized (n=64) screen failures (n=36) placebo (n=16)gbr 830 (n=46) completed (n=8)completed (n=26) itt/safety (n=16) biological activity set (n=11)b itt/safety (n=46)a biological activity set (n=29)b did not receive study drug (n=2) discontinued withdrawal of consent adverse event protocol violation required rescue medication lost to follow-up other 22* 11 2 1 4 1 3 discontinued withdrawal of consent adverse event protocol violation required rescue medication lost to follow-up other 8 2 1 0 4 0 1 *includes subjects who did not receive gbr 830 (n=2). aexcludes subjects from the randomized population (gbr 830, n=2) who did not receive ≥1 partial or full dose of study drug. bexcludes subjects from the itt population (gbr 830, n=17; placebo, n=5) who did not receive both doses of study drug and have ≥1 post-baseline skin biopsy (day 29 or day 71). itt, intent-to-treat. ◾◾ demographic and baseline characteristics were generally similar between treatment groups in the itt/safety and bas populations (table 1) table 1. baseline characteristics itt bas gbr 830 (n = 46) placebo (n = 16) gbr 830 (n = 29) placebo (n = 11) demographics age, years mean ± sd 36.2 ± 13.4 40.4 ± 15.1 34.1 ± 12.2 40.7 ± 14.7 median (min, max) 34 (18, 66) 41 (19, 59) 33 (18, 61) 42 (19, 59) sex, n (%) male 21 (45.7) 11 (68.8) 16 (55.2) 8 (72.7) female 25 (54.3) 5 (31.2) 13 (44.8) 3 (27.3) race, n (%) asian 5 (10.9) 2 (12.5) 4 (13.8) 2 (18.2) black or african american 9 (19.6) 3 (18.7) 5 (17.2) 1 (9.1) white 31 (67.4) 11 (68.8) 19 (65.5) 8 (72.7) other 1 (2.2) 0 1 (3.4) 0 body mass index, mean ± sd, kg/m2 26.1 ± 4.1 26.2 ± 3.7 25.7 ± 3.7 26.1 ± 3.9 baseline disease characteristics bsa affected, mean ± sd, % 38.6 ± 23.4 39.3 ± 21.5 38.6 ± 24.0 38.4 ± 21.6 easi mean ± sd 25.1 ± 12.3 23.3 ± 9.4 25.4 ± 13.7 22.2 ± 9.6 median (min, max) 21.0 (12.4, 65.0) 19.9 (14.1, 47.5) 20.1 (12.7, 65.0) 18.9 (14.1, 47.5) epidermal thickness (lesional), μm mean ± sd na na 140.6 ± 57.6 125.0 ± 47.0 median (min, max) na na 130.2 (58.4, 287.4) 136.9 (60.8, 187.1) epidermal thickness (non-lesional), μm mean ± sd na na 63.3 ± 25.2 59.0 ± 21.5 median (min, max) na na 56.8 (29.5, 155.6) 54.2 (33.1, 96.0) bas, biological activity set; bsa, body surface area; easi, eczema area and severity index; itt, intent-to-treat; na, not applicable; sd, standard deviation. adverse events (safety population) ◾◾ teaes occurred with similar incidence between treatment groups (table 2); most were mild or moderate in intensity table 2. treatment-emergent adverse events (safety population) adverse events, n (%) gbr 830 (n = 46) placebo (n = 16) deaths 0 0 any teae 29 (63.0) 10 (63.0) any serious ae 1 (2.2)a 0 discontinuation due to aes 2 (4.3) 1 (6.3) common teaesb headache 6 (13.0) 4 (25.0) dermatitis atopic 6 (13.0) 2 (12.5) nasopharyngitis 4 (8.7) 2 (12.5) upper respiratory tract infection 4 (8.7) 2 (12.5) post-procedural infection 4 (8.7) 0 myalgia 3 (6.5) 0 asubject had coronary artery occlusion (not related to study treatment). breported in ≥5% of subjects in the gbr 830 group. ae, adverse event; teae, treatment-emergent adverse event. biomarker signatures (bas population) ◾◾ significant decreases from baseline in ox40+ t-cell and ox40l+ dc cellular staining in lesional skin were found with gbr 830 treatment at day 29 (p<0.05) and day 71 (p<0.001) (figure 3) •◾ drug versus placebo trended on significance at day 71 for both markers figure 3. ox40 target expression from representative gbr 830and placebo-treated subjects figure 4 immunohistochemistry staining of ox40 (a) and ox40l (b) at baseline and after treatment (day 29 and day 71); protein expression is shown in red staining and the images in each line were taken from the same subject. mean fold change (fch) from baseline in ox40 expression (c) and ox40l expression (d). +p<0.1, *p<0.05, **p<0.01, ***p<0.001. ◾◾ gbr 830-treated subjects had significant reductions from baseline in epidermal thickness (figure  4a, 4d), k16 mrna expression  (figure 4b, 4e), and ki67+ cells at days 29 and 71 (figure 4c, 4f) •◾ changes from baseline with placebo were not signif icant (thickness, k16) or less pronounced (ki67+) figure 4. epidermal proliferation at baseline and after treatment figure 5 panels show (a) h&e staining, (b) k16 staining, and (c) ki67 staining showing epidermal hyperplasia at baseline lesions; the images for both drug and placebo panels were taken from a representative subject for each. mean fold change (fch) from baseline is shown for (d) epidermal thickness, (e) k16 mrna expression measured by rt-pcr, and (f) ki67 protein expression measured by immunohistochemistry. +p<0.1, *p<0.05, **p<0.01, ***p<0.001. h&e, hematoxylin and eosin; k16, keratin16; rt-pcr, real-time polymerase chain reaction. ◾◾ gbr 830-treated subjects had significant reductions in most mrna biomarkers of disease activity compared with baseline and placebo (figure 5) figure 5. changes in quantitative rt-pcr mrna expression following treatment day 29 day 71 day 29 day 71 day 29 day 71 day 29 day 71 day 29 day 71day 29 day 71 day 29 day 71 day 29 day 71 day 29 day 71 day 29 day 71 8 0 4 f c h ( vs . b a se lin e ) -4 a. ifnγ 5.0 2.5 0 -2.5 f c h ( vs . b a se lin e ) -5.0 b. cxcl10 0 4 f c h ( vs . b a se lin e ) -4 -8 d. ccl11 4 0 f c h ( vs . b a se lin e ) -4 e. ccl17 4 0 2 f c h ( vs . b a se lin e ) -2 -4 f. tslpr 5.0 2.5 0 -2.5 f c h ( vs . b a se lin e ) -5.0 c. il-31 5.0 0 2.5 f c h ( vs . b a se lin e ) -2.5 g. il-23p19 -5 0 -10 f c h ( vs . b a se lin e ) -15 -20 h. il-8 5.0 0 2.5 f c h ( vs . b a se lin e ) -2.5 -5.0 -7.5 i. s100a9 5 0 -5 f c h ( vs . b a se lin e ) -10 j. s100a12 gbr 830 placebo th1 th2 th17/th22 mrna expression of representative inflammatory markers of th1 (a-b), th2 (c-f), and th17/th22 (g-j) pathways in subjects treated with gbr 830 compared with baseline and placebo. +p<0.1, *p<0.05, **p<0.01, ***p<0.001. mrna, messenger ribonucleic acid; rt-pcr, real-time polymerase chain reaction. clinical efficacy (itt population) ◾◾ a greater proportion of gbr 830-treated subjects achieved easi 50 versus placebo at day 29 (43.6% vs 20.0%; p=0.2) and day 71 (76.9% vs 37.5%; p=0.02) ◾◾ gbr 830-treated subjects demonstrated greater percentage change in easi from baseline through day 85 compared with placebo (figure 6) ◾◾ a positive association was seen between improvements in clinical assessments and changes in tissue ad biomarkers figure 6. percentage change in easi from baseline through day 85 (itt population) 0 -25 e a s i, % c h a n g e f ro m b a se lin e -50 baseline day 4 day 8 day 15 day 22 day 29 day 32 day 36 day 50day 43 day 57 day 71 day 85 gbr 830 placebo stars indicate intravenous dose administration. +p<0.1, *p<0.05. easi, eczema area and severity index; itt, intent-to-treat. conclusions ◾ gbr 830 was safe and well tolerated, with a similar teae profile to placebo ◾ gbr 830 inhibits the ox40/ox40l pathway, as shown through reduced expression of ox40/ox40l in lesional skin ◾ treatment with gbr 830 resulted in reductions in epidermal hyperplasia, proliferation, and mrna biomarkers for disease activity, indicating an effect on both the acute and chronic stages of ad ◾ although the study was not powered for statistical testing, subjects treated with gbr 830 had improvements in ad scores that were consistent with biomarker results ◾ results of this proof-of-concept study indicate that gbr 830 may be an effective treatment for ad r e f e r e n c e s 1. webb gj, hirschfield gm, lane pj. clin rev allergy immunol. 2016;50:312-32. 2. hanifin jm, reed ml. dermatitis. 2007;18:82-91. 3. suarez-farinas m, ungar b, correa da rosa j, et al. j allergy clin immunol. 2015;135:1218-27. 4. esaki h, ewald da, ungar b, et al. j allergy clin immunol. 2015;135:153-63. 5. ewald da, malajian d, krueger jg, et al. bmc med genomics. 2015;8:60. d i sc losu r e s this study was funded by glenmark pharmaceuticals, sa. medical writing and editorial assistance were provided by prescott medical communications group, chicago, il. p r e s e nte d at th e fa ll c li n i c a l d e r m ato lo gy co n f e r e n c e o c to b e r 18-21, 2018 | l a s v e g a s , n v skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 358 brief articles iohexol-induced acute generalized exanthematous pustulosis (agep): case report irina lerman, phd1, william h. sipprell, md2, glynis a. scott, md2, christopher t. richardson, md, phd2. 1university of rochester school of medicine and dentistry, rochester, ny. 2department of dermatology, university of rochester medical center, rochester, ny. a 75-year-old woman with a longstanding history of angioimmunoblastic t-cell lymphoma (aitl) presented for dermatologic evaluation after developing a widespread pruritic rash of two weeks duration. she reported the itching and rash were initially localized to her arms but spread to the thighs, legs, chest, and back over several days. she was now complaining of a burning sensation in her inner arms, worsening redness, and swelling of the hands. she was otherwise feeling well, and review of systems was entirely unremarkable. notably, she denied fever, chills, and recent infections. aitl was originally diagnosed in 2008, with subsequent recurrence in 2009, 2016, and most recently 2017. at time of presentation, she had received four brentuximab cycles with good tolerance over the course of two months. she underwent computed tomography (ct) imaging with iohexol abstract acute generalized exanthematous pustulosis (agep) is a rare adverse drug reaction characterized by numerous non-follicular sterile pustules overlying edematous, erythematous plaques. the majority of agep cases are associated with antimicrobial medications, although other agents and etiologies have also been implicated. here, we report a patient with recurrent angioimmunoblastic t-cell lymphoma (aitl) who presented with a pruritic and widespread pustular eruption one week following computed tomography (ct) with iohexol contrast administration. notably, she had a documented prior mild reaction to contrast medium and was appropriately pre-medicated with diphenhydramine and prednisone before imaging. biopsy revealed intra-epidermal pustules, epidermal spongiosis, and dermal infiltrate of lymphocytes, neutrophils, and some eosinophils – histological findings consistent with agep. systemic and topical corticosteroids plus topical mupirocin resulted in complete resolution of symptoms. while cutaneous reactions to iodinated contrast are common and often self-limited, severe manifestations such as agep must be considered particularly in patients with a history of prior contrast allergy. case report skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 359 contrast agent to assess tumor response one week prior to the cutaneous eruption. importantly, she had a reported allergy to contrast dye, documented as a ‘mild rash’. she was given 50 mg diphenhydramine at 1 hour before and 50 mg prednisone at 1, 7, and 13 hours before the ct scan, as instructed by guidelines for pre-medication in patients with contrast allergy.1 she had previously taken prednisone without incident. her only other medication was rivaroxaban, which she had been taking for over a year. no recent changes were made to her medication regimen. dermatologic history was significant for excised stage pt1a melanoma, squamous cell carcinoma in situ, actinic keratosis, and lentigo. she had no personal history of eczema or psoriasis. exam was notable for scaly salmon-red papules coalescing into eczematous plaques studded with numerous pustules on the upper chest, upper back, and bilateral upper extremities (figure 1). on the lower back beneath the waistband line, bilateral lateral thighs, and posterior knees, there were deep-red papules coalescing to plaques studded with numerous pustules. bilateral upper arms and dorsal hands were edematous. open fissures on flexural surface of arms appeared impetiginized. palms and soles were uninvolved. punch biopsies were performed on the lateral thigh and upper arm. sections demonstrated intra-epidermal pustules associated with mild epidermal spongiosis. papillary dermis showed marked edema with separation of the epidermis from the dermis with a mixed inflammatory infiltrate of lymphocytes, neutrophils, and some eosinophils (figure 2). findings were consistent with a pustular drug eruption / hypersensitivity reaction, also known as acute generalized exanthematous pustulosis (agep).2 although less likely, pustular psoriasis was included in the histologic differential diagnosis. of note, bacterial organisms were identified within the pustules focally, and wound culture grew 1+ methicillin-susceptible staphylococcus aureus, consistent with our clinical suspicion of impetiginization. indeed, a potential complication of agep includes impetiginization, particularly in older or immunocompromised individuals.3 complete blood count revealed leukocytosis with neutrophilia, consistent with a neutrophilmediated inflammatory process of agep.4 complete metabolic panel was within normal limits, and there were no signs of organ involvement. the patient was recommended to continue 60 mg prednisone taper and apply triamcinolone 0.1% and mupirocin 2% ointment twice daily. on follow up one week later, she exhibited significant improvement in erythema involving bilateral upper extremities, upper chest, and upper back compared to prior exam. bilateral arms and hands were significantly less edematous, and linear superficial lesions were in the process of healing. there were scattered pink papules and plaques with minimal scaling on the thighs, but no pustules were noted anywhere on the skin. her rash further improved and fully resolved by three months of topical steroid use, which is longer than standard agep therapy, indicating severe manifestation.5 she continued to tolerate brentuximab infusions with excellent aitl response and no relapse of pustular rash. future avoidance of contrast dye was strongly recommended, as re-exposure could again precipitate agep.2 skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 360 agep is a rare adverse pustular eruption with 1 to 5 cases per 1 million, usually associated with antibiotics – particularly beta-lactams and macrolides.6 additional medications like antifungals, anticonvulsants, and antihypertensives have also been implicated.7 in this report, we are the first to present a case of iohexol-induced agep despite prophylactic prednisone in a patient with previously documented mild contrast allergy. differential diagnosis included acute generalized pustular psoriasis (von zumbusch) due to the overlapping clinical presentation with agep. interestingly, pustular psoriasis may be precipitated by abrupt withdrawal of systemic corticosteroids or worsened by systemic corticosteroid therapy – which was not observed in our patient.8 moreover, most cases occur in the setting of diagnosed psoriasis, and generalized malaise, fever, and arthralgia are common. histologic features distinguishing agep from pustular psoriasis include absence of tortuous, dilated blood vessels in the papillary dermis and absence of psoriasiform changes.2 while agep is primarily characterized by non-follicular sterile pustules, bacterial super-infection may develop as seen in our patient and must be appropriately treated to prevent further morbidity.3 iodinated contrast agents are utilized in roughly 50 million imaging procedures every year and are often necessary for accurate diagnosis. patients with mild contrast dye allergy who require contrast for diagnostic purposes are pre-medicated with prednisone to reduce risk of acute (i.e. urticarial) adverse cutaneous reactions.1 however, data on the efficacy of corticosteroids in preventing delayed adverse reactions discussion figure 2. histopathology reveals an intraepidermal pustule associated with mild epidermal spongiosis and lymphocytic infiltrate with neutrophils and some eosinophils within the papillary dermis. findings are consistent with agep. magnification 100x. figure 1. extensive papules coalescing to eczematous plaques studded with numerous pustules involving the upper chest, upper extremities (a), upper back, lower back (b), and lateral thighs (c). dorsal hands were edematous and appeared impetiginized (d). a b c d skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 361 (dars) are inadequate.9 indeed, prophylactic prednisone was ineffective at averting agep in our patient. this may be attributed to the unique pathogenesis of agep via a t cell-mediated type iv hypersensitivity reaction that is distinct from other dars.9 in conclusion, this interesting case augments the limited literature on iohexol-induced cutaneous reactions and encourages clinicians to consider agep as part of their differential diagnosis in dars to contrast media.10-12 conflict of interest disclosures: none funding: none corresponding author: irina lerman, phd irina_lerman@urmc.rochester.edu references: 1. delaney a, carter a, fisher m. the prevention of anaphylactoid reactions to iodinated radiological contrast media: a systematic review. bmc medical imaging 2006; 6: 2. 2. feldmeyer l, heidemeyer k, yawalkar n. acute generalized exanthematous pustulosis: pathogenesis, genetic background, clinical variants and therapy. international journal of molecular sciences 2016; 17. 3. sidoroff a, halevy s, bavinck jn, vaillant l, roujeau jc. acute generalized exanthematous pustulosis (agep)--a clinical reaction pattern. journal of cutaneous pathology 2001; 28: 113119. 4. britschgi m, pichler wj. acute generalized exanthematous pustulosis, a clue to neutrophilmediated inflammatory processes orchestrated by t cells. current opinion in allergy and clinical immunology 2002; 2: 325-331. 5. kley c, murer c, maul jt, meier b, anzengruber f, navarini aa. rapid involution of pustules during topical steroid treatment of acute generalized exanthematous pustulosis. case reports in dermatology 2017; 9: 135-139. 6. thienvibul c, vachiramon v, chanprapaph k. five-year retrospective review of acute generalized exanthematous pustulosis. dermatology research and practice 2015; 2015: 260928. 7. de a, das s, sarda a, pal d, biswas p. acute generalised exanthematous pustulosis: an update. indian journal of dermatology 2018; 63: 22-29. 8. westphal dc, schettini ap, souza pp, castiel j, chirano ca, santos m. generalized pustular psoriasis induced by systemic steroid dose reduction. anais brasileiros de dermatologia 2016; 91: 664-666. 9. egbert re, de cecco cn, schoepf uj, mcquiston ad, meinel fg, katzberg rw. delayed adverse reactions to the parenteral administration of iodinated contrast media. ajr american journal of roentgenology 2014; 203: 1163-1170. 10. atasoy m, erdem t, sari ra. a case of acute generalized exanthematous pustulosis (agep) possibly induced by iohexol. the journal of dermatology 2003; 30: 723-726. 11. hammerbeck aa, daniels nh, callen jp. ioversol-induced acute generalized exanthematous pustulosis: a case report. archives of dermatology 2009; 145: 683-687. 12. peterson a, katzberg rw, fung ma, woottongorges sl, dager w. acute generalized exanthematous pustulosis as a delayed dermatotoxic reaction to iv-administered nonionic contrast media. ajr american journal of roentgenology 2006; 187: w198-201. poster presented at the 36th fall clinical dermatology conference | las vegas, nv | october 12-15, 2017 open-label study (arido) evaluating long-term safety of topical glycopyrronium tosylate (gt) in patients with primary axillary hyperhidrosis dee anna glaser,1 adelaide a. hebert,2 alexander nast,3 william p. werschler,4 stephen shideler,5 lawrence green,6 richard d. mamelok,7 janice drew,8 john quiring,9 david m. pariser10 1saint louis university, st. louis, mo; 2uthealth mcgovern medical school, houston, tx; 3charité–universitätsmedizin berlin, berlin, germany; 4premier clinical research, spokane, wa; 5shideler dermatology and skin care center, carmel, in; 6george washington university school of medicine, washington, dc; 7mamelok consulting, palo alto, ca; 8dermira, inc., menlo park, ca; 9qst consultations, allendale, mi; 10eastern virginia medical school and virginia clinical research, inc., norfolk, va introduction • hyperhidrosis affects an estimated 4.8% of the us population or approximately 15.3 million people,1 and the impact of hyperhidrosis on quality of life is reported as comparable to, or greater than, psoriasis or eczema2 • topical glycopyrronium tosylate (gt; formerly drm04) is a cholinergic receptor antagonist being developed for the treatment of primary axillary hyperhidrosis in patients ≥9 years of age • gt has been assessed in 2 replicate, randomized, double-blind, vehicle-controlled pivotal phase 3 lead-in trials (atmos-1 and atmos-2) – gt was generally well tolerated and demonstrated clinically meaningful improvements in disease severity and reductions in sweat production through 4 weeks in these trials3 • this 44-week, open-label extension study (arido; nct02553798) assessed the long-term safety of gt in patients with primary axillary hyperhidrosis who completed atmos-1 (nct02530281; sites in the us and germany) or atmos-2 (nct02530294, sites in us only) methods study design • arido was a 44-week open-label extension of atmos-1/atmos-2, 4-week, double-blind, phase 3 clinical trials in which patients with primary axillary hyperhidrosis were randomized 2:1 to gt (3.75% topical solution) or vehicle applied once daily to each axilla for 28 days (figure 1) – patients who completed atmos-1/atmos-2 with ≥80% treatment compliance were eligible to continue into arido and receive open-label gt for 44 weeks or to early termination (et; figure 1) • eligible patients were ≥9 years of age (patients <16 years were only recruited at us sites) and had primary axillary hyperhidrosis for ≥6 months, with gravimetrically-measured sweat production of ≥50 mg/5 min in each axilla, axillary sweating daily diary (asdd; for patients ≥16 years of age) or asdd-children (asdd-c; for patients <16 years of age) axillary sweating severity item (item 2)4 score ≥4 (0 to 10 numeric rating scale), and hyperhidrosis disease severity scale (hdss) ≥3 • patients were excluded for history of a condition that could cause secondary hyperhidrosis; prior surgical procedure or treatment with a medical device for axillary hyperhidrosis; treatment with iontophoresis within 4 weeks or treatment with botulinum toxin within 1 year for axillary hyperhidrosis; axillary use of nonprescription antiperspirants within 1 week or prescription antiperspirants within 2 weeks; new or modified psychotherapeutic medication regimen within 2 weeks; treatment with medications having systemic anticholinergic activity, centrally acting alpha-2 adrenergic agonists, or beta-blockers within 4 weeks unless dose had been stable ≥4 months and was not expected to change; and/or conditions that could be exacerbated by study medication figure 1. study design wk 0 randomization baselinea wk 4 wk 49 end of study screening double-blind treatment 44-week open-label extension arido atmos-1 and atmos-2 target recruitment: 330 patients randomized 2:1 gt gt 564 (86.6%) patients continued into arido vehicle wk 48 abaseline for arido was week 0 of atmos-1/atmos-2 gt, topical glycopyrronium tosylate; wk, week assessments • primary objective was long-term safety – safety was evaluated via treatment-emergent adverse events (teaes) through week 45 (week 44 + 1 week safety follow-up), local skin reactions (lsrs) through week 44, laboratory testing, vital signs, and physical examinations – teaes are summarized overall from baseline in atmos-1/atmos-2 to week 45 (up to 48 weeks of gt) and by duration of exposure to gt in both atmos-1/atmos-2 and arido • descriptive efficacy assessments evaluated in arido were an extension of the primary endpoints in atmos-1/atmos-2 – change from baseline in atmos-1/atmos-2 in gravimetrically-measured sweat production at week 44 (up to 48 weeks of gt) – change from baseline in atmos-1/atmos-2 in hdss responder rate (≥2-grade improvement) at week 44 (up to 48 weeks of gt) • all safety and efficacy analyses were performed on the safety population (patients receiving ≥1 dose of gt and having ≥1 post-baseline assessment in arido) results • the majority of patients (86.6%; n=564) completing atmos-1/atmos-2 (369 patients [65.4%] had received gt, and 195 [34.6%] had received vehicle) continued into arido (figure 2) • of the patients enrolled in arido, most patients were female (55.3%) and white (83.3%) with a mean age of 33.0 years and mean bmi of 27.3 kg/m2 (table 1) figure 2. patient disposition gt n=369 gt n=564 n=226 (40.1%) vehicle n=195 eligible atmos-1/atmos-2 participants who entered arido (n=564) completed week 44 of arido early discontinuation lost to follow-up consent withdrawn adverse event noncompliance pregnancy protocol violation physician decision 232 92 82 44 8 3 2 1 patients at <week 44 when study objectives were achieved a 106 astudy objectives were achieved gt, topical glycopyrronium tosylate table 1. demographics and baselinea disease characteristics (safety populationb) gt (n=550) demographics age (years), mean ± sd 33.0 ± 11.4 age group, n (%) ≥16 years <16 years 522 (94.9) 28 ( 5.1) female, n (%) 304 (55.3) white, n (%) 458 (83.3) bmi (kg/m2), mean ± sd 27.3 ± 5.0 baseline disease characteristics sweat production (mg/5 min),c mean ± sd 164.7 ± 145.0 hdss,d,e n (%) grade 3 grade 4 348 (63.3) 201 (36.5) quality of life dlqi,f mean ± sd cdlqi,g mean ± sd 11.4 ± 5.9 8.9 ± 5.4 abaseline in atmos-1/atmos-2 bpatients receiving ≥1 dose of gt and having ≥1 post-baseline assessment in arido cgravimetrically-measured average from the left and right axillae dhdss ≥3 was an inclusion criteria en=549; 1 subject entered atmos-2 with hdss=2, which was a protocol violation fpatients ≥16 years of age gpatients <16 years of age bmi, body mass index; cdlqi, children’s dlqi; dlqi, dermatology life quality index; gt, topical glycopyrronium tosylate; hdss, hyperhidrosis disease severity scale; sd, standard deviation efficacy assessments • through week 44/et in arido (up to 48 weeks of gt), gt-treated patients continued to demonstrate improvements in efficacy measures, including sweat production and hdss responder rate (figure 3) – from baseline in atmos-1/atmos-2 to week 44/et in arido, mean sweat production decreased by 95.7 ± 140.8 mg/5 min, which was maintained from a decrease of 107.6 ± 207.2 mg/5 min in gt-treated patients after 4 weeks in atmos-1/atmos-2 (figure 3a) – at week 44/et in arido, hdss responder rate (≥2-grade improvement) was 63.2%, a further improvement from 59.1% in gt-treated patients at week 4 in atmos-1/atmos-2 • hdss grade improved by 1, 2, and 3 grades in 30.9%, 46.7%, and 16.5% of patients, respectively (figure 3b) figure 3. mean sweat production and hdss improvement from baselinea to week 44/et (safety populationb) baseline (n=550) 164.7 week 44/et (n=430) 63.1 mean cfb: -95.7 ± 140.8 none 5.9% 1 grade 30.9% 2 grades 46.7% 3 grades 16.5% improvement 350 300 250 200 150 100 50 -100 -50 0 m e a n s w e a t p r o d u c t io n ( m g /5 m in ) a. sweat production c 100 80 60 40 20 0 p r o p o r t io n o f s u b je c t s ( % ) b. hdss improvement d abaseline in atmos-1/atmos-2 bpatients receiving ≥1 dose of gt and having ≥1 post-baseline assessment in arido cgravimetrically-measured average from the left and right axillae dn=437 cfb, change from baseline; et, early termination; hdss, hyperhidrosis disease severity scale safety assessments • after 48 weeks, 329 (59.8%) patients reported ≥1 teae, though most were mild or moderate in severity (table 2) • a total of 44 (8.0%) patients discontinued due to a teae and 7 (1.3%) reported ≥1 serious teae (table 2) • prespecified anticholinergic teaes of interest were reported in 78 (14.2%) patients; most were mild or moderate in severity and were able to be managed by dose interruption (table 2) – 37 patients reported 45 vision blurred events; 40 (88.9%) were bilateral – 29 patients reported 37 mydriasis events; 31 (83.8%) were unilateral • generally, teaes, including teaes prespecified as anticholinergic teaes of interest, did not increase over time with longer duration of exposure (table 3) • 179 (32.5%) of patients reported lsrs, which were typically mild or moderate in severity (figure 4) • there were no clinically meaningful changes in laboratory parameters or vital signs table 2. summary of treatment-emergent adverse events from baselinea to week 45/et (safety populationb) gt (n=550) any teae, n (%) 329 (59.8) any serious teae, n (%) 7 ( 1.3)c discontinuation due to a teae, n (%) 44 ( 8.0) deaths, n (%) 0 most frequently reported teaes (>5% patients), n (%) dry mouth vision blurred application site pain nasopharyngitis mydriasis 93 (16.9) 37 ( 6.7) 35 ( 6.4) 32 ( 5.8) 29 ( 5.3) prespecified anticholinergic teaes of interest, n (%) vision blurred mydriasis urinary hesitation nocturia urine flow decreased hypermetropia pollakiuria pupils unequal 78 (14.2) 37 ( 6.7)d 29 ( 5.3)e 23 ( 4.2) 2 ( 0.4) 2 ( 0.4) 1 ( 0.2) 1 ( 0.2) 1 ( 0.2) any teaes (n=329) teaes by severity, n (%) mild moderate severe 148 (45.0) 153 (46.5) 28 ( 8.5) relation to study drug, n (%) not related related 131 (39.8) 198 (60.2) numbers in table represent the number of patients reporting ≥1 teae, not number of events abaseline in atmos-1/-2 bpatients receiving ≥1 dose of gt and having ≥1 post-baseline assessment in arido cinfectious colitis, affective disorder, suicide attempt, mydriasis, chest pain, concussion, diverticulitis d37 patients reported 45 vision blurred events; 40 (88.9%) were bilateral e29 patients reported 37 mydriasis events; 31 (83.8%) were unilateral et, early termination; gt, topical glycopyrronium tosylate; teae, treatment-emergent adverse event table 3. summary of frequently reported teaes and teaes of special interest (safety population)a,b teaes, n (%) duration of exposure 0 to 4 weeks (n=550) >4 to 8 weeks (n=537) >8 to 20 weeks (n=479) >24 to 36 weeks (n=417) >36 weeks to es (n=365) any teae 176 (32.0) 148 (27.6) 102 (21.3) 78 (18.7) 59 (16.2) teaes reported in >5% of patients dry mouth vision blurred application site pain nasopharyngitis mydriasis 59 (10.7) 11 ( 2.0) 16 ( 2.9) 14 ( 2.5) 8 ( 1.5) 23 ( 4.3) 14 ( 2.6) 9 ( 1.7) 9 ( 1.7) 8 ( 1.5) 19 ( 4.0) 7 ( 1.5) 5 ( 1.0) 4 ( 0.8) 9 ( 1.9) 15 ( 3.6) 5 ( 1.2) 6 ( 1.4) 5 ( 1.2) 5 ( 1.2) 5 ( 1.4) 4 ( 1.1) 3 ( 0.8) 3 ( 0.8) 2 ( 0.5) prespecified anticholinergic teaes of interest vision blurred mydriasis urinary hesitation nocturia urine flow decreased hypermetropia pollakiuria pupils unequal 11 ( 2.0) 8 ( 1.5) 14 ( 2.5) 2 ( 0.4) 1 ( 0.2) 0 0 1 ( 0.2) 14 ( 2.6) 8 ( 1.5) 4 ( 0.7) 0 1 ( 0.2) 0 0 0 7 ( 1.5) 9 ( 1.9) 4 ( 0.8) 0 0 0 0 0 5 ( 1.2) 5 ( 1.2) 2 ( 0.5) 0 0 1 ( 0.2) 1 ( 0.2) 0 4 ( 1.1) 2 ( 0.5) 1 ( 0.3) 0 0 0 0 0 ain atmos-1/atmos-2 and arido combined bpatients receiving ≥1 dose of gt and having ≥1 post baseline assessment on arido numbers in table represent the number of patients reporting ≥ teae, not number of events es, end of study; gt, topical glycopyrronium tosylate; teae, treatment-emergent adverse event figure 4. summary of local skin reactions by severity from baselinea to week 44/et (safety populationb) any (n=179) 44 (25%) 120 (67%) 15 (8%) erythema (n=116) 27 (23%) 81 (70%) 8 (7%) burning/stinging (n=73) 24 (33%) 42 (58%) 7 (10%) pruritis (n=68) 26 (38%) 31 (46%) 11 (16%) dryness (n=48) 8 (17%) 39 (81%) 1 (2%) edema (n=34) 8 (24%) 24 (71%) 2 (6%) scaling (n=25) 5 (20%) 20 (80%) mild moderate severe 200 160 120 80 40 0 n um be r of l s r s patients were counted as having an lsr if any post-baseline assessment was mild, moderate, or severe abaseline in atmos-1/atmos-2 bpatients receiving ≥1 dose of gt and having ≥1 post-baseline assessment in arido gt, topical glycopyrronium tosylate; lsr, local skin reaction conclusions • safety results were consistent with anticholinergic treatment and with the safety profile observed in prior gt studies,3 with no new or unexpected findings – most teaes were mild or moderate in severity and considered by the investigator to be related to study drug – a low number of subjects discontinued due to a teae – while approximately one-third of patients reported lsrs, most were mild or moderate in severity – incidence of teaes, including prespecified anticholinergic teaes of interest, did not increase with long-term treatment • efficacy measures obtained at the end of treatment in arido indicated that subjects had maintained sweat production reduction and less bothersome sweating compared with baseline in atmos-1/atmos-2 • gt was generally well tolerated and improvements in efficacy measures were maintained in patients with primary axillary hyperhidrosis when applied once daily to both axillae over a maximum of 48 weeks references 1. doolittle et al. arch dermatol res. 2016;308(10):743-9. 2. hamm. dermatol clin. 2014;32(4):467-76. 3. pariser et al. poster presented at: 25th european academy of dermatology and venerology congress; september 28-october 2, 2016; vienna, austria. 4. glaser et al. poster presented at: 13th maui derm for dermatologists congress; march 20-24, 2017; maui, hi. acknowledgements this study was funded by dermira, inc. medical writing support was provided by prescott medical communications group (chicago, il). all costs associated with development of this abstract were funded by dermira, inc. author disclosures dag: consultant and investigator for dermira, inc. aah: consultant for dermira, inc.; employee of the university of texas medical school, houston, which received compensation from dermira, inc. for study participation. an: employee of charité – universitätsmedizin berlin, which received compensation from dermira, inc. for study participation. wpw: consultant and investigator for dermira, inc. ss: investigator for dermira, inc. lg: consultant and investigator for dermira, inc.; investigator for brickell. rdm: consultant for dermira, inc. jd: employee of dermira, inc. jq: employee of qst consultations.dmp: consultant and investigator for dermira, inc. fc17posterglaseropenlabelstudyarido.pdf modulation of the mu and kappa opioid axis for the treatment of chronic pruritus sarina elmariah, md, phd1, sarah chisolm, md2, thomas sciascia, md3, shawn g. kwatra, md4 1massachusetts general hospital, boston, ma, usa; 2emory university department of dermatology, atlanta, ga, usa; va visn 7, usa; 3trevi therapeutics, new haven, ct, usa; 4johns hopkins university school of medicine, baltimore, md, usa introduction • conditions such as uremic pruritus (up) and prurigo nodularis are characterized by chronic pruritus, which negatively impacts quality of life (qol), sleep, and mood1-7 • opioid receptors and their endogenous ligands are involved in the regulation of itch, with activation of mu (µ) opioid receptors (mors) causing itchy skin and activation of kappa (κ) opioid receptors (kors) reducing itch (figure 1)8-10 – unlike mor agonists, mor antagonists and kor agonists are not associated with addictive potential11-13 • imbalances in the mor and kor systems in the skin or central nervous system are thought to contribute to the pathophysiology of severe chronic pruritus14-18 • accordingly, targeting mors and kors represents an active area of research for novel treatments14,16 figure 1. different consequences of activation of mors and kors8,10 activation of mors • respiratory depression • pruritus • constipationanalgesia gi/go activation of kors dysphoria• analgesia • antipruritic effect • reduced inflammation gi/go gi/go, gi/go protein; kor, kappa (κ) opioid receptor; mor, mu (µ) opioid receptor. objective • to provide a narrative overview of studies supporting opioid receptor agonists and/or antagonists in chronic pruritus methods • the pubmed database was searched to identify englishlanguage literature on the role of opioid receptor agonists and/or antagonists in chronic pruritus in the past decade – search terms included (pruritus or itch), opioid, (kappa or mu), and (agonist or antagonist) – select references cited within identified publications were noted as well • findings from relevant publications were summarized as a narrative review presented at the 2021 winter clinical dermatology conference–hawaii® results • in the united states, opioid receptor–targeting agents have been used off-label to treat chronic itch19 • several agents that target mors and kors are being used off-label or are in clinical development for the treatment of chronic itch associated with various disease states (figure 2) figure 2. agents targeting mors and kors3,16,19 antagonist antagonist agonistagonist naltrexone (oral) nalfurafine (oral) difelikefalin (iv) butorphanol (intranasal) nalbuphine (oral) mor mor korkor iv, intravenous; kor, kappa (κ) opioid receptor; mor, mu (µ) opioid receptor. mor antagonist naltrexone • an observational study (n=18) of the mor antagonist naltrexone (50 mg/d), used off-label for the treatment of severe itch of varying etiologies, including prurigo nodularis, demonstrated efficacy based on change in visual analog scale (vas) scores (figure 3)20 – 16 patients (88.9%) experienced symptomatic improvement – 5 patients (27.8%) reported adverse events (aes), including insomnia, fatigue, constipation, and anorexia figure 3. effects of mor antagonist naltrexone on pruritus (varying etiologies) based on change in vas scores in patients ≥65 years of age (n=18)20 2 (11.1%) 3 (16.7%) 13 (72.2%) 7 6 persistent pruritus improved much improved (>50% reduction in pruritus intensity) almost complete elimination of itch mor, mu (µ) opioid receptor; vas, visual analog scale. kor agonists nalfurafine • nalfurafine is a kor agonist approved in japan for the treatment of up3 – a phase 3, randomized, placebo-controlled, double-blind study of oral nalfurafine (2.5 µg, 5 µg) in hemodialysis patients with up (n=337) demonstrated significant differences vs placebo on the primary endpoint of vas scores (figure 4)21 – the most frequent ae was insomnia figure 4. change in vas scores from baseline (preobservation period) to last 7 days of treatment with kor agonist nalfurafine vs placebo for uremic pruritus21 –23* –22† –13 -25 -20 -15 -10 -5 0 nalfurafine 2.5 µg (n=112) nalfurafine 5 µg (n=114) placebo (n=111) ls m ea n c h an ge in v a s sc or es kor, kappa (κ) opioid receptor; ls, least squares; vas, visual analog scale. *p=0.0001 vs placebo. †p=0.0002 vs placebo. difelikefalin • two randomized, double-blind, placebo-controlled trials evaluated the peripherally acting kor agonist difelikefalin in hemodialysis patients with moderate-to-severe up22,23 – phase 2 study (nct02858726): in 174 patients with up randomly assigned to receive iv difelikefalin 0.5, 1.0, or 1.5 µg/kg or placebo 3 times a week, difelikefalin (all doses combined) significantly reduced itch intensity (worst itching intensity numeric rating scale [wi-nrs]) scores from baseline to week 8 compared with placebo (primary outcome; p=0.002)22 – phase 3 study (nct03422653): compared with placebo, a significantly greater proportion of patients treated with iv difelikefalin 0.5 µg/kg 3 times a week achieved the primary endpoint of ≥3-point improvement in wi-nrs scores from baseline to week 1223 – itch-related qol was improved in both trials, and the most common aes were diarrhea, dizziness, and nausea/vomiting, with most being mild or moderate combination mor antagonists/kor agonists butorphanol • a case series (n=16) demonstrated efficacy of intranasal mor antagonist/kor agonist butorphanol (10 mg/ml as needed up to every 4 hours) used off-label for the treatment of chronic refractory pruritus24 – most patients (13/16; 81.3%) improved on the basis of wi-nrs scores and/or patient reports, with a ≥4-point decrease in itch scores among 6 patients (1 patient had no improvement, and 2 were lost to follow-up) – significant improvements on measures of qol (dermatology life quality index, skindex-10 survey) and depressive symptoms (beck depression inventory) were observed – 3 patients reported aes (insomnia, lightheadedness, lethargy) nalbuphine • a phase 2/3, randomized, placebo-controlled, double-blind study (nct02143648) included 373 hemodialysis patients with moderate-to-severe up; 120/373 received the oral mor antagonist/kor agonist nalbuphine (nal) 120 mg (dose based on molecular weight, including active drug and salts) extended-release (nal-er) tablets twice daily (bid) and demonstrated significant and durable itch-intensity reductions (primary endpoint) vs placebo (figure 5)25 – in a patient subgroup with severe up (n=179), sleep disruption attributed to itching improved significantly vs placebo (p=0.006) – the most common reason for discontinuing treatment was gastrointestinal side effects (eg, nausea, vomiting) during titration figure 5. mor antagonist/kor agonist nalbuphine in uremic pruritus: change in worse itching intensity (wi-nrs scores) from baseline to last 2 treatment weeks25 –3.5* –3.1 –2.8 nal-er 120 mg bid (n=120) nal-er 60 mg bid (n=128) placebo bid (n=123) bid, twice daily; nal-er, nalbuphine extended-release; wi-nrs, worst itching intensity numeric rating scale. *p=0.017 vs placebo. • a phase 2, randomized, double-blind, placebo-controlled trial and open-label extension (nct02174419) evaluated nal-er in patients with moderate-to-severe prurigo nodularis26 – in the modified intent-to-treat population, the proportion of patients with ≥30% response for wi-nrs scores at week 10 was numerically greater with nal-er 162 mg bid (44.4%) than with nal-er 81 mg bid (27.3%) or placebo (36.4%), although the differences were not statistically significant – patients who received nal-er 162 mg bid and completed 10 weeks of doubleblind treatment had significant improvements in pruritus symptoms (≥30% and ≥50% reductions in 7-day average itch intensity nrs scores; figure 6), itchrelated qol (p=0.022), and healing of skin lesions – most patients who completed 26 and 50 weeks of open-label treatment experienced improvement in excoriation/crusting and/or healing of skin lesions – during the double-blind study, aes consisted of nausea and dizziness (38.9%, n=7 each) and headache (27.8%, n=5); most aes were mild or moderate and occurred during titration figure 6. mor antagonist/kor agonist nalbuphine in prurigo nodularis: proportion of study completers with ≥30% and ≥50% reduction in 7-day average itch intensity nrs scores vs baseline26 20.0% 0 10 20 30 40 50 60 70 80 90 100 ≥30% reduction in 7-day average itch intensity nrs vs baseline ≥50% reduction in 7-day average itch intensity nrs vs baseline r es po n de rs (% ) nal-er 81 mg bid (n=18) nal-er 162 mg bid (n=12) placebo bid (n=20) 61.1% 83.3%* 40.0% 20.0% 50.0%† 44.4% bid, twice daily; kor, kappa (κ) opioid receptor; mor, mu (µ) opioid receptor; nal-er, nalbuphine extendedrelease; nrs, numeric rating scale. *p=0.008 vs placebo. †p=0.028 vs placebo. conclusions • these data suggest that agents that modulate underlying neurologic components of pruritus through µ-antagonism and/or κ-agonism are effective and safe options for the treatment of chronic pruritus • these agents have low abuse potential and generally appear well tolerated, with the most commonly reported aes being insomnia and gastrointestinal effects disclosures financial arrangements of the authors with companies whose products may be related to the present report are listed below, as declared by the authors. dr. elmariah has received honoraria or consulting fees for her participation as an advisory board member, scientific advisor and/or consultant for trevi therapeutics, menlo therapeutics, rapt therapeutics and sanofi pharmaceuticals. she is also an investigator for the prism trial by trevi therapeutics. dr. chisolm has received research and/or consulting support from companies including trevi therapeutics, menlo therapeutics, abbvie, janssen pharmaceuticals, kiniksa pharmaceuticals, and pfizer. itch-e has received support from sanofi pharmaceuticals, pfizer, and genentech. dr. sciascia is an employee of trevi therapeutics and may own stock or stock options. dr. kwatra is an advisory board member/consultant for abbvie, galderma, incyte corporation, pfizer inc., regeneron pharmaceuticals, and kiniksa pharmaceuticals and has received grant funding from galderma, pfizer inc. and kiniksa pharmaceuticals. acknowledgments this review was sponsored by trevi therapeutics, new haven, ct, usa. medical writing and editorial assistance were provided to the authors by peloton advantage, llc, an open health company, and funded by trevi therapeutics. all authors met the icmje authorship criteria. no honoraria were paid for authorship. references 1. tsianakas a, et al. curr probl dermatol. 2016;50:94-101. 2. ramakrishnan k, et al. int j nephrol renovasc dis. 2013;7:1-12. 3. fowler e, yosipovitch g. acta derm venereol. 2020;100(2):adv00027. 4. rehman iu, et al. medicina (kaunas). 2019;55(10). 5. satti mz, et al. cureus. 2019;11(7):e5178. 6. todberg t, et al. acta derm venereol. 2020;100(8):adv00119. 7. janmohamed sr, et al. arch dermatol res. 2020. 8. tubog td, et al. j perianesth nurs. 2019;34(3):491-501.e8. 9. kardon ap, et al. neuron. 2014;82(3):573-86. 10. valentino rj, volkow nd. neuropsychopharmacology. 2018;43(13):2514-20. 11. noble f, et al. br j pharmacol. 2015;172(16):3964-79. 12. beck tc, et al. pharmaceuticals (basel). 2019;12(2). 13. wang s. cell transplant. 2019;28(3):233-8. 14. phan nq, et al. acta derm venereol. 2012;92(5):555-60. 15. bigliardi-qi m, et al. dermatology. 2005;210(2):91-9. 16. yosipovitch g, et al. j allergy clin immunol. 2018;142(5):1375-90. 17. kupczyk p, et al. acta derm venereol. 2017;97(5):564-70. 18. wieczorek a, et al. j eur acad dermatol venereol. 2020;34(10):2368-72. 19. fowler e, yosipovitch g. ann allergy asthma immunol. 2019;123(2):158-65. 20. lee j, et al. ann dermatol. 2016;28(2):159-63. 21. kumagai h, et al. nephrol dial transplant. 2010;25(4):1251-7. 22. fishbane s, et al. kidney int rep. 2020;5(5):600-10. 23. fishbane s, et al. n engl j med. 2020;382(3):222-32. 24. khanna r, et al. j am acad dermatol. 2020;83(5):1529-33. 25. mathur vs, et al. am j nephrol. 2017;46(6):450-8. 26. data on file, trevi therapeutics, new haven, ct, usa. synopsis: acne vulgaris remains an extremely common skin condition with minimal advancement in treatment strategies. a need for novel therapies that are convenient and effective remains. objective: the objective of this study was to evaluate the efficacy of the 1064nm nd:yag laser with a 650-microsecond pulse duration in the treatment of acne vulgaris. methods: 10 patients (fitzpatrick skin type i-iv) with acne vulgaris on the face resistant to standard acne regimens or those looking for alternative therapies were treated with the 1064nm nd:yag laser with a 650-microsecond pulse duration. treatments were performed on average every 1-4 weeks for 3 to 7 treatments. the laser treatment protocol included 3 passes on the entire face with 3-6 stacked pulses on active lesions. results: improvement of acne lesions occurred as early as 3 weeks post-treatment, with the majority of subjects clearing after 4 treatment sessions. treatments were very well tolerated with no reported pain during or after treatment. conclusions: advantages of this laser modality include essentially no pain or downtime and the ability to safely treat all skin types with acne vulgaris. the 1064nm nd:yag laser with a 650-microsecond pulse duration is a safe and effective alternative treatment option for acne vulgaris. the mechanism of action is thought to be due to reduction of sebum output, inflammation and destruction of bacteria, but further studies are warranted. a clinical evaluation of the 1064nm nd:yag laser with a 650-microsecond pulse duration for the treatment of acne vulgaris tanya greywal1*, nazanin saedi, md2, md, arisa ortiz, md1 1uc san diego health, san diego, ca (*at time study was conducted); 2dermatology associates of plymouth meeting, plymouth meeting, pa disclosures: dr. ortiz and saedi are members of the aerolase medical advisory board figure 1 a) figure 3 b) figure 2 a) figure 1 b) figure 2 b) figure 3 a) figure 1 a) 17 y.o. female with resistant acne on tretinoin 0.025% cream, clindamycin 1% gel and benzoyl peroxide 5% wash. b) clearance after 4 treatments with the 1064 nm nd:yag laser with a 650microsecond pulse duration. figure 2 a) 20 y.o female with resistant acne on doxycycline 100 mg po bid, tretinoin 0.05% cream, and benzoyl peroxide 5% wash. b) clearance after 4 treatments with the 1064 nm nd:yag laser with a 650-microsecond pulse duration. figure 3 a) 21 y.o. female with resistant acne on tretinoin 0.025% cream and clindamycin 1% lotion. b) clearance after 4 treatments with the 1064 nm nd:yag laser with a 650-microsecond pulse duration. fcd.castle.restage.092818.4x4.submitted improvement of risk assessment in cutaneous melanoma (cm) by a prognostic 31-gene expression profile (31-gep) test over ajcc-based staging alone giselle prado, md1, robert w. cook, phd2, kyle r. covington, phd2, federico a. monzon, md, fcap2, darrell rigel, md, faad3 1national society for cutaneous medicine, new york, ny; 2castle biosciences, inc., friendswood, tx; 3new york university school of medicine, new york, ny background results results references • a substantial number of melanoma-related deaths occur in patients originally diagnosed with early american joint committee on cancer (ajcc) stage disease, suggesting aggressive tumor biology despite having clinicopathologic features associated with low-risk disease. • a 31-gene expression profile (31-gep) test has been developed and validated in retrospective and prospective studies1-8 to predict 5-year metastatic risk from primary cutaneous melanoma (cm) tumor tissue with a high degree of technical reliability.9 • the 31-gep test classifies melanoma as class 1a (lowest risk), class 1b (low risk), class 2a (increased risk), or class 2b (highest risk). • this prognostic information is used to inform patient management decisions, including frequency of follow-up and surveillance imaging, referrals, sentinel lymph node biopsy guidance, and consideration of adjuvant therapy.10-15 31-gep test class 1 low risk (1a lowest) class 2 high risk (2b highest) stage i-iii melanoma •archival formalin-fixed paraffin-embedded cm tumor samples from 18 u.s. centers (n=690, stage i-iii) along with clinical, pathological, and outcomes data for each case were collected under an irbapproved protocol1-4. stage i-ii cases were restaged according to ajcc 8th edition criteria. •the 31-gep test was performed in a cap-accredited/clia-certified laboratory using high-throughput rt-pcr assays as previously described1-5. •the kaplan-meier method was used to estimate 5-year recurrence-free (rfs; time to either a regional or distant metastatic event), distant metastasis-free (dmfs; time to any metastatic event beyond the regional nodal basin), and melanoma-specific survival (mss; time from diagnosis to death documented as from melanoma) rates with significance determined by log-rank test. all non-recurrent cases had at least 5 years of follow-up. •class 1aand 2b-predicted mss outcomes for each stage were compared to rates associated with ajcc 8th edition stage16. •based on national comprehensive cancer network (nccn) guidelines for surveillance and follow-up, ajcc binary low and high-risk groups are defined as stage i-iia and stage iib-iv, respectively. cox multivariate regression analysis for mss was performed comparing ajcc binary risk and 31-gep test results. methods figure 1. stage-specific survival rates for the 31-gep cohort align with the ajcc 8th edition database survival rates ajcc 8th ed. cohort14 stage (n) 5-year i (10974) 98% ii (4717) 90% iii (4622) 77% years since diagnosis m el an om as pe ci fic s ur vi va l ( % ) 0 5 10 100 80 60 40 20 0 ajcc 8th ed. cohort1631-gep cohort with 8th ed. staging 31-gep cohort ajcc 8th edition16 earliest diagnosis year 1998 1998 number of collaborating centers 18 10 percent of cases from u.s. centers 100% 34% 31-gep cohort with 8th ed. staging 0 5 10 years since diagnosis m el an om as pe ci fic s ur vi va l ( % ) stage (n) 5-year i (344) 98.5% ii (138) 90.7% iii (208) 75.8% 100 80 60 40 20 0 time (years) % r e c u rr e n c e f re e rfs p<0.0001 time (years) % d is ta n t m e ta s ta s is f re e dmfs p<0.0001 time (years) % s u rv iv a l mss p<0.0001 class (n) 5-year rfs (95% ci) 5-year dmfs (95% ci) 5-year mss (95% ci) 1a (312) 90% (87-93%) 94% (91-97%) 99% (98-100%) 1b (80) 81% (73-90%) 85% (77-93%) 95% (90-100%) 2a (84) 68% (58-79%) 75% (66-85%) 91% (85-98%) 2b (214) 37% (31-44%) 50% (43-58%) 75% (69-83%) class 1a class 1b class 2a class 2b figure 2. 31-gep results identify significantly different risk groups4 figure 3. addition of 31-gep test results improves risk obtained by ajcc 8th edition staging alone stage i stage ii stage iii class (n) 5-year mss (95% ci) event rate class (n) 5-year mss (95% ci) event rate class (n) 5-year mss (95% ci) event rate 1a (249) 99.6% (98.8-100%) 0.4% 1a (21) 100% (100-100%) 0% 1a (42) 94.8% (88.0-100%) 7% 2b (19) 89.5% (76.7-100%) 11% 2b (83) 84.7% (76.3-94.1%) 13% 2b (112) 61.2% (50.1-74.7%) 28% *for surveillance and follow-up purposes, nccn guidelines propose dividing patients into binary risk groups based on ajcc stage: low (stage i-iia) and high risk (stage iib-iv). cox multivariate regression analysis n=690 58 events mss hr (95% ci) p value ajcc high risk 4.84 (2.3-10.1) <0.0001 gep class 1b 3.38 (0.9-12.8) 0.073 gep class 2a 4.67 (1.3-16.4) 0.02 gep class 2b 10.1 (3.4-16.4) <0.0001 stage i ii iii m el an om as pe ci fic s ur vi va l ( % ) low risk stage i-iia high risk stage iib-iii 99.6% ≈ia 89.5% ≈iia/iib 100% ≈ia 84.7% ≈iib/iic 94.8% ≈iia 61.2% ≈iiic+ 98% ajcc binary risk category 100 90 80 70 60 class 1a class 2b ajcc mss 90% 77% conclusions • in the study cohort of stage i-iii melanoma cases1-4 with similar survival outcomes to the 8th edition ajcc cohort, the 31-gep test result was able to add information to further stratify patients with lower and higher risks than predicted by clinicopathologic staging alone. multivariate analysis demonstrated that a 31-gep class 2b result was an independent predictor of mss with a greater hazard ratio than ajcc binary risk. • as accurate risk assessment is important for patient management decisions, use of the 31-gep test can help guide these choices, including follow-up, sentinel lymph node biopsy guidance, surveillance and possible adjuvant therapy, as has been previously published10-15. to determine the impact on risk prediction when results from the 31-gep test are used with ajcc 8th edition staging. objective the authors wish to acknowledge the following collaborating physicians and institutions for their contributions to this study: drs. sancy leachman and john vetto, oregon health and science university, drs. pedram gerami and jeff wayne, northwestern university, drs. jane messina and jonathan zager, moffitt cancer center, dr. rene gonzalez, university of colorado cancer center, drs. david lawson, keith delman, and maria russell, emory university, dr. stephen lyle, university of massachusetts medical school, dr. gilchrist jackson, kelsey-seybold clinic, dr. anthony greisinger, kelsey research foundation, dr. lee cranmer, university of arizona cancer center, dr. t. christopher windham, florida hospital memorial medical center, dr. lewis kaminester, dermatology north palm beach, dr. martin fleming, university of tennessee health science center, drs. laura ferris and jonhan ho, university of pittsburgh medical center, dr. alexander miller, start center for cancer care, dr. sarah estrada, affiliated dermatology, dr. jason robbins, pathology associates, dr. david pariser, pariser dermatology specialists, dr. brian gastman, cleveland clinic and dr. daniel rosen, baylor college of medicine. 1. gerami p, et al. clin cancer res 2015;21:175-83. 2. gerami p, et al. j am acad dermatol 2015;72:780-5 e783. 3. zager js, et al. bmc cancer 2018;18(1):130. 4. gastman br, et al. jaad 2018; doi: 10.1016/j.jaad.2018.07.028. 5. hsueh ec, et al. j hematol oncol 2017;10:152. 6. greenhaw b, et al. dermatol surg 2018; 7. renzetti m, et al. society of surgical oncology annual meeting. 2017. 8. hsueh ec, et al. j clin oncol 2016; 34(15_suppl):9565. 9. cook rw et al. diagn pathol. 2018;13(1):13. 10. svoboda rm et al. j drugs dermatol. 2018;17(5):544. 11. berger ac et al. curr res med opin 2016;32(9):1599-604. 12. dillon ld et al. skin: j cut med 2018;2(2):111-21. 13. cook rw et al. winter clinical dermatology conference. 2018. 14. schuitevoerder d et al. j drugs dermatol 2018;17(2):196-199. 15. farberg as et al. j drugs dermatol 2017;16(5):428-431. 16. gershenwald et al. ca cancer j clin 2017;67(6):472-492. acknowledgements funding & disclosures this study was sponsored by castle biosciences, inc., which provided funding to contributing centers for tissue and clinical data retrieval. rwc, krc, & fam are employees and options holders of castle biosciences, inc. gp is a fellow with the national society for cutaneous medicine which receives funding from castle biosciences, inc. dr is a consultant for castle biosciences, inc. powerpoint presentation calcipotriene plus betamethasone dipropionate (0.005%/0.064%) foam and apremilast: matching-adjusted indirect comparison and us cost per responder analyses martin erik nyeland, phd1, lidia becla, msc1, dharm s. patel, phd2, karen a. veverka, phd2, andrine r. swensen, phd2 1leo pharma a/s, ballerup, denmark; 2leo pharma inc., madison, new jersey background results conclusions methodology acknowledgements references  new and effective topical treatments and systemic treatments with improved safety for the treatment of plaque psoriasis have blurred the distinction among treatment options, particularly for patients who may be considered for either topical treatment or non-biologic systemic treatment present with a broad range of symptoms and factors.  calcipotriene and betamethasone dipropionate 0.005%/0.064%) foam is a fixed-combination, once-daily topical treatment for adult patients with plaque psoriasis.1  apremilast is a twice-daily oral treatment for patients with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy.2  despite overlap in studied populations, head-to-head clinical trials and comparative analyses have not been conducted between cal/bd foam and apremilast. study design (figure 1)  matching-adjusted indirect comparisons (maics) use individual patient data (ipd) from trials of one treatment to match baseline summary statistics reported from trials of another treatment to compare treatment outcomes across a balanced patient population.3  published clinical trials with sufficiently similar populations and outcomes to support indirect comparisons were identified for cal/bd foam and apremilast.  priority baseline variables for matching included disease severity (psoriasis area and severity index, pasi, or body surface area, bsa), quality of life, demographics, duration of psoriasis, body mass index, and history of topical treatment.  maic analysis was conducted between cal/bd foam and apremilast4 and associated economic evaluation through us cost per responder analysis. figure 1. methodology of maic analysis of cal/bd foam and apremilast4  weighted analyses of response rate variables pga and pasi 75 were conducted with ipd from pooled cal/bd foam trials and aggregated results from the other treatment study using a logistic model and 95% confidence intervals (cis)  sensitivity analyses were completed to investigate results by comparison to phase 3 pso-able cal/bd trial data from week 4 and week 12. statistical analysis exclusion criteria for comparator trials:  mean pasi or mean bsa ≥15 [suitability range 3-15] to ensure comparability between cal/bd foam and apremilast study populations with moderate disease  combination therapy treatment approaches due to difficulty in isolating effect of one treatment  no efficacy measures available limiting any comparative effectiveness comparisons  no baseline demographics and/or disease characteristics available preventing adequate matching of study populations  time points of efficacy measures not specified limiting comparative efficacy comparisons inclusion criteria for comparator trials:  apremilast had to be studied, over time either retrospectively or prospectively  manuscript languages: english, danish, swedish or norwegian  apremilast investigated for plaque psoriasis comparator trial used in maic:  based on inclusion and exclusion criteria, and overlap of studied populations, only one study of apremilast (unveil9) met the criteria and was included in the maic analysis (table 1)  this analysis used matching-adjusted indirect comparison to balance study populations in terms of baseline characteristics in a comparative efficacy and cost per responder evaluation.  results demonstrate that cal/bd foam has higher pga 0/1 and pasi-75 response rates and a lower cost per pasi-75 responder in the us than apremilast in adult patients with moderate plaque psoriasis. table 2. spga 0/1 efficacy response rates calculated via maic between cal/bd foam and apremilast.4  after matching study populations, 52.7% of patients treated with cal/bd foam achieved spga 0/1 at week 4 vs. 30.4% treated with apremilast at week 16 (p<0.001). table 3. pasi75 efficacy response rates calculated via maic between cal/bd foam and apremilast.4 poster presented at the fall clinical dermatology conference, las vegas, nevada, october 18-21th, 2018 figure 2. average cost per pasi-75 responder for cal/bd foam and apremilast based on the maic analysis.  in the us, cost per pasi-75 response cal/bd foam is $3,770, and is lower than cost per response for apremilast ($66,671). this study was sponsored by leo pharma. table 4. economic evaluation of cal/bd foam for 4 weeks and apremilast for 16 weeks for treatment of moderate plaque psoriasis through a cost per pasi-75 responder analysis. objective conduct a matching-adjusted indirect comparison (maic) analysis to compare individual patient data from available study populations for cal/bd foam with aggregate patient characteristics and treatment outcomes from published efficacy assessments of apremilast in adult patients with moderate plaque psoriasis. potential matching variable (priority) pooled data 5-8 unveil9 treatment cal/bd foam apremilast study design randomized, double-blind controlled study phase iv randomized study dosing qd 30 mg bid n 749​ 148 sex, male (%) 470 (62.8%)​ 74 (50.0%) mean age (sd) 51.4 (14.1)​ 48.6 (15.4) mean bmi (sd) 31.2 (7.2)​ 30.5 (7.4) mean bsa (sd) 7.3 (6.1)​ 7.2 (1.6) years of psoriasis (sd) 16.8 (14.0)​ 17.5 (13.9) mean pasi (sd) 7.3 (4.6)​ 8.2 (4.0) mean dlqi (sd) 11.0 (6.5) bsa x pga (sd) 21.9 (20.5)​ 21.8 (5.3) prev. topical treatment, yes 637 (85.1%) 122 (82.4%) prev. syst treatment, yes 233 (31.1%) table 1. identification of cal/bd foam and apremilast trials for maic analysis4 pooled data5-8 unveil9 treatment cal/bd foam apremilast before re-weighting after reweighting effective sample size, n 748 640 148 bmi 31.2 30.5 30.5 pasi 7.3 8.2 8.2 previous topical treatment 85.1% 82.4% 82.4% pga 0/1 responder, % (95% ci) 56.4% (51.9%; 60.9%) 52.7% (44.9%; 60.4%) 30.4% (23.6%; 38.2%) p-value (t-test) p<0.001 pooled data5-8 unveil9 treatment cal/bd foam apremilast before re-weighting after reweighting effective sample size, n 748 651 148 age 51.3 48.6 48.6 bmi 31.2 30.5 30.5 previous topical treatment 85.1% 82.4% 82.4% pasi-75 responder, % (95% ci) 51.4% (51.2%, 51.5%) 51.1% (50.5%, 51.7%) 21.6% (15.8%, 28.9%) p-value (t-test) p<0.001  after matching study populations, 51.1% of patients treated with cal/bd foam achieved pasi-75 at week 4 vs. 21.6% treated with apremilast at week 16 (p<0.001). pasi 75 treatment period[weeks] consumption per treatment period pack cost # units per pack unit unit per pack price per unit cal/bd foam 51.1% 4 117.1 g* $987.09 $1974.18 1 2 60 g 60 g x 2 60-120 g $16.45 per g apremilast 21.6% 16 6570 mg** $1012.5 3939.71 27-60 10-30 mg 6901800 mg $2.19 per mg data source maic (table 2) approved fda indication *4 pooled cal/bd studies **fda indication analysource®, accessed april 2018 (third party provider of wac pricing data)  cost per responder analysis was conducted based on the regimens approved by the fda using us drug pricing. o apremilast dosing per treatment 6570 mg over 16 weeks2 o cal/bd foam dosing per treatment average consumption data in 4 phase ii/iii trials5-8; 117.1 g over 4 weeks  cost per treatment period was calculated by multiplying the drug wac per unit dose (mg or g, respectively) with total dosing (apremilast) or average consumption (cal/bd foam) over treatment period.  cost per pasi-75 responder was calculated by multiplying cost per treatment period by proportion of patients achieving pasi-75, as calculated in the maic analysis4. limitations  comparative safety analyses and associated economic impact were not conducted.  wac prices do not reflect manufacturer rebates, are not reflective of actual spend, and are dated for april 2018.  time to response difference between cal/bd foam (4 weeks) and apremilast (16 weeks) precluded use of the same treatment time horizon.  analyses based on clinical trials may not be generalizable to the real world.  imbalance in sample size exists due to applicable publications on comparator, and may not be fully addressed by methodology.  additional head-to-head research should be conducted to confirm the comparative efficacy findings. 1. enstilar® foam [package insert]. madison, nj: leo pharma inc. 2. otezla® tablets [package insert]. summit, nj: celgene corporation. 3. signorovitch,je, sikirica v, erder mh, et al. value in health. 2012;12:940-947. 4. bewley aa, et al. eur acad dermatol venereol annual congress 2018. p1927. 5. paul c et al. j eur acad dermatol venereol. 2017;31(1):119-126 6. leonardi c et al. j drugs dermatol. 2015;14(12):1468-1477 7. lebwohl m, et al. j am acad dermatol. 2015; 72 (5 suppl 1): ab222 8. koo j et al. j dermatol treat. 2016;27(2);120-127 9. strober b, et al. j drugs dermatol. 2017;16(8):801-808. bmi, body mass index; bsa, body surface area; pasi, psoriasis area and severity index; dlqi, dermatology life quality index; pga, physician’s global assessment; qd, once daily; bid, twice daily slide number 1 skin july oa 1216 proof returned skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 363 original research the hidden impact of molluscum contagiosum: a survey of caregivers’ experiences with diagnosis, treatment, and impact on quality of life pearl kwong md, phd1, adelaide a. hebert md2, collette utley dnp, np-c3, melissa olivadoti phd4 1solutions through advanced research, jacksonville, fl 2uthealth mcgovern medical school, houston, tx 3gold skin care center, nashville, tn 4verrica pharmaceuticals inc., west chester, pa molluscum contagiosum (molluscum) is a common cutaneous viral infection that primarily affects children, the immunocompromised, and sexually active adults. molluscum is the third most common viral skin infection in children and one of the five most prevalent skin diseases worldwide.1 the largest epidemiology study in children documented an average of 13.3 months to resolution without intervention; 30% of cases persisted at 1.5 years, and 13% at 2 years.2 abstract objective: molluscum contagiosum (molluscum) is considered benign and self-limiting. however, the caregiver and patient experience largely remains a mystery. this online survey aimed to collect caregivers’ views on their experiences with molluscum infection in their children, including diagnosis, treatment, and the impact of the virus on the caregivers’ and their child’s life. methods: parents, caregivers, and/or legal guardians (ages 18+, 20% male and 80% female) of children diagnosed with molluscum in the past 4 years (ages 3-16 years of age) answered a 15-minute paid online survey with questions about their experience with molluscum. results: caregivers (n=150) were mostly caucasian (85%), 25-44 years of age (87%) and had at least one child with active molluscum (75%) at the time of the survey. the average number of health care providers (hcps) consulted for molluscum was 1.95 and diagnosis was made by a variety of hcp types. the spread of molluscum to ≥ 1 child in the household was reported by 60% of caregivers in multi-child households. the average number of treatments used were 2.36 including hcp-administered treatments and consumer products. caregivers reported moderate to major impact on their lives (62%) or their child’s life (74%) due to molluscum. limitations: questions were not validated, recall time was up to 4 years. conclusions: molluscum patients may receive a diagnosis from many sources. caregivers may utilize more than one treatment modality to help clear the infection including consumer products. molluscum can cause an impact on quality of life for affected children and their caregivers. introduction skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 364 molluscum may be associated with pain, itching, eczema, and secondary bacterial infections. reasons for treatment of molluscum include alleviating discomfort, reducing risk of autoinoculation and spread to others, preventing scarring, and elimination of social stigma.3,4 a survey of u.s. physicians found that the treatment of molluscum varies widely.5 there are no fdaapproved treatments for molluscum, and non-approved treatments vary in safety and efficacy. the lack of treatment guidelines, safety concerns with current treatments, and the categorization of the infection as “benign” and “self-limiting”3,5 may lead physicians to wait for natural clearance.3 the choice of active non-intervention by physicians may be insufficient for caregivers, leading caregivers to take matters into their own hands. however, the habits of caregivers in attempting to treat the virus at home, including the use of consumer products or mechanical techniques (such as disturbing the lesions at home), have not been documented to date. there are few studies reporting quality of life (qol) concerns with molluscum and most are small or use generalized methods that may not highlight the unique concerns for molluscum patients and caregivers. in a study of parents of 30 children with molluscum, braue et al.6 reported molluscum moderately or greatly concerned 43% of children with the infection, along with 82% of their parents. concerns were focused on physical issues such as scarring, itching, the chance of spread to peers, pain, and effects of treatment. in a larger study on qol of a variety of skin diseases using the children’s dermatology quality of life index (cdlqi)2, olsen and colleagues reported an impact of 3.5 on a scale from 1-30 (n=5) for molluscum patients, which suggests a small impact of the disease. however, the questions on the cdlqi may not be representative of the daily struggles that patients with molluscum or their caregivers face. for example, children with molluscum do not always experience itchy, sore, or painful skin with molluscum, may be able to hide the molluscum under clothing making it less obvious to friends/family, and there is no evidence that molluscum causes sleep loss or loss of school time. thus, simply due to the type of questions asked on these measures, they may not be sensitive to the issues of the molluscum patient and may downplay the impact of the disease. further measures are needed to elucidate the concerns of the caregiver and the patient. these questions do not shed light on the patient journey including diagnosis and treatment details. this survey sought to uncover more information about the type and number of health care professionals (hcps) seen for diagnosis, treatment patterns, and at-home remedy use, as well as the potential social stigma and impact of the disease on the patient and caregiver. this voluntary survey was conducted using an online quantitative methodology from march 25th to april 2nd, 2020, among caregivers (parents and guardians) of children diagnosed with molluscum by a physician. potential respondents were reached via a commercially available online panel sourced through whitman insight strategies. whitman insight strategies identified potential respondents and conducted the surveys. individuals agreed to participate not knowing what potential surveys will be about. respondents were pre-recruited through a variety of procedures including random-digit-dialing, email invitation from a partner website/isp, or methods skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 365 client. in this survey, potential participants were emailed a link that directs them to a website where they were screened to determine if they qualified based on the outlined criteria and were then asked survey questions and paid for completing the survey. at survey initiation, the respondents gave written consent for their survey responses to be used and shared in future market research. respondents were required to be above 18 years of age and required to have at least one child who was diagnosed with molluscum by a physician in the past 4 years between 3 years and 16 years of age in the home. the survey targeted 80% female respondents and 20% male respondents to ensure appropriate representation of the gender of caregivers. questions asked of the caregivers are listed in table 1. question topics included the types of hcps that were consulted or had diagnosed the child with molluscum, incidence of spread of molluscum to another child in the home, the type of information shared with the caregiver by the doctor, impact on the caregivers’ lives, impact on patients’ lives, treatment modalities and at-home remedies, and demographics of the survey participants (table 1). the margin of error at the 95% confidence interval for the total sample was ± 7.7%. demographics the survey included 154 respondents who were caregivers of children diagnosed with molluscum. most caregivers (75%, n=115/154) had children with an active infection, whereas 25% (n=39/154) had children with molluscum in the past 4 years but did not currently have an infection. most respondents were caucasian (85%, n=131/154) with a median age of 36 (range 23-57), with a median home size of 4 (range 2-7), and with a median child age of 8 (range 1-16). further demographic data can be found in table 2. diagnosis of molluscum caregivers consulted many different types of hcps about their child’s molluscum, including dermatologists (42% n=65/154), emergency room physicians (27%, 41/154), family practice physicians (40%, 62/154), infectious disease specialists (29%, 45/154), and pediatricians (56%, 76/154). the hcp type that diagnosed the condition included a dermatologist (34%, 52/154), emergency room physician (21%, 32/154), family practice physician (37%, 57/154), infectious disease specialist (23%, 36/154), and pediatrician (49%, 76/154) (table 3). the average number of physicians a caregiver consulted was 1.95 (table 3). when asked if it was challenging to find a doctor who would tell caregivers about treatment options and be willing to treat their child, 51% (79/154) agreed, 19% (29/154) were neutral, and 30% (47/154) disagreed. when being counseled about molluscum by an hcp after diagnosis, 49% (76/154) of caretakers reported the hcp told them molluscum was caused by a poxvirus, with 79% (122/154) being told that because of the infectious nature of the virus, there should be steps taken to avoid exposure to others. a total of 55% (84/154) of caregivers remember being told by a physician that molluscum could be upsetting for themselves and their affected children, and 50% (77/154) were told the molluscum would go away on its own. results skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 366 table 1. questions asked of caregivers about their child’s molluscum question answers which of the following health care practitioners did you consult after you noticed the bump(s)?* dermatologist emergency room physician family practice physician infectious disease specialist pediatrician other which of the following health care practitioners told you your child has molluscum or diagnosed your child with molluscum?* dermatologist emergency room physician family practice physician infectious disease specialist pediatrician other you mentioned you have more than one child under the age of 16 in your household. has molluscum ever spread from one child to the other within your household? yes no don’t know which of the following do you remember the doctor telling you?* molluscum is caused by a poxvirus since molluscum is contagious, we should take steps to avoid it molluscum can be upsetting for caregivers and children there are treatments for molluscum that we can consider molluscum will go away on its own none of the above how much of an impact has the molluscum had on your [affected] child’s life? no impact minor impact moderate impact major impact how much of an impact has the molluscum had on your [the caregiver’s] life caring for your child with the infection? no impact minor impact moderate impact major impact how much do you agree or disagree with the following statement? i worried about what other people thought about our family having a child with molluscum strongly disagree somewhat disagree neutral somewhat agree strongly agree how much do you agree or disagree with the following statement? molluscum kept my child away from doing the things they love strongly disagree somewhat disagree neutral somewhat agree strongly agree how much do you agree or disagree with the following statement? it was challenging to find a doctor who would tell me about treatment options and be willing to treat my child strongly disagree somewhat disagree neutral somewhat agree strongly agree which of the following best reflects the doctor’s recommendation when your child was first diagnosed with molluscum? the doctor recommended we let molluscum run its course and heal on its own the doctor told us about treatment options skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 367 which of the following ways of dealing with the molluscum did you decide on for your child* cryotherapy or cryosurgery (i.e. the doctor freezes off each bump with liquid nitrogen) curettage (i.e. the doctor pierces the bump and scrapes off the skin with a small tool) cantharidin or beetle juice (i.e. doctor applies a liquid that causes blistering) home remedies molluscum treatment from amazon or drug store with no rx required squeezing and/or removing the bumps or material inside the bumps by myself other (specify) *questions where respondents were allowed to choose all answers that applied sixty percent (65/108) of caregivers with more than one child in the home reported spread of the infection from one child to another. a total of 76% (117/154) caregivers remember their doctor telling them there are treatment options to consider. treatment modalities a large majority (76%, 117/154) of caregivers were told by an hcp that there were treatments to consider whereas 61% (94/154) had treatment options explained to them. a total of 39% (60/154) of caregivers reported that an hcp recommended they let the infection run its course. the average number of treatments utilized per caregiver response was 2.36. twenty-seven percent (42/154) of caregivers reported that they considered removing the lesions themselves at home, and 20% (30/154) of caregivers strongly considered doing so. many modalities were eventually used to treat the infection, including cryosurgery (41%, 63/154), curettage (31%, 47/154), compounded cantharidin (39%, 60/154), home remedies (43%, 66/154), molluscum therapies from a pharmacy or online store (44%, 68/154), and squeezing and/or removing the lesions or the core of the lesions at home (31%, 48/154), or other (7%, 11/154) (figure 1). under “other”, respondents included letting it run its course (n=7), prescription creams from a physician (n=2), not decided yet (n=1), and creams and bleach baths (n=1) (figure 1). impact of molluscum on the caregiver and patient in responding to the statement “molluscum kept my child away from doing the things they love,” 71% (109/154) of caregivers responded with agreement, 14% (22/154) were neutral, and 15% (24/154) disagreed. the majority of caregivers (62%, 95/154) worried about what people thought about their family having a child with molluscum (figure 3). caregivers also reported an impact on their lives caring for a child with molluscum, expressing mostly major (25%, 38/154) or moderate impact (38%, 58/154) (figure 3). when asked about the impact on their children’s lives, 26% (41/154) of caregivers responded with major impact, and 47% (73/154) responded with moderate impact (figure 3). previous smaller studies have shown that molluscum can impact caregivers and their children with molluscum. however, the level of impact and information on the journey of the caregivers and child in seeking resolution of the disease is limited due to smaller studies with less sensitive measures.2,6 this survey elucidates important information on the journey to diagnosis and treatment, as well as the impact on quality of life of the patient and their caregiver. caregivers reported seeing multiple hcps for a diagnosis and treatment, and some reported that it could be a challenge to find an hcp that was willing to treat their child. this could discussion skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 368 table 2. survey respondent demographics and characteristics respondents (n=154) household information median number of people in the home – no. (range) 4 (2-7) household size – no. (%) 2-3 people 44 (28) 4-5 people 94 (61) 6+ people 16 (10) mean age of children in the home in years – yrs. (range) 8 (1-16) age of children in the home – no. (%)* ≤ 3 years 48 (31) 4-8 years 80 (52) 9-12 years 77 (50) 13-16 years 67 (43) caregiver gender – no. (%) male 31 (20) female 123 (80) molluscum status – no. (%) child currently has molluscum 115 (75) child had molluscum in the last 4 years 40 (25) spread of molluscum from one child to another in the home** 65 (60) ethnicity – no. (%) white/caucasian 131 (85) black/african american 16 (10) asian 6 (4) native hawaiian/pacific islander 1 (1) american indian/alaskan native 2 (1) other 3 (2) homestead information – no. (%) city 79 (51) suburb 65 (42) small town/rural 10 (7) *caregivers could have more than one child in the home **in homes of >1 child (n=108) table 3. diagnosis and treatment responses n=154 average number of physicians consulted per caregiver 1.95 type of hcp – no. (%)* consulted for diagnosis diagnosed molluscum dermatologist 65 (42) 52 (34) er physician 41 (27) 32 (21) family practice physician 62 (40) 57 (37) infectious disease specialist 45 (29) 36 (23) pediatrician 87 (56) 76 (49) hcp treatment recommendations – no. (%) active nonintervention 60 (39) offered treatment options 94 (61) suggest either lack of hcp knowledge on the molluscum diagnosis, a need for a referral to a specialist for identification or specialized treatment, or a choice by the hcp to allow the infection to run its course leading to “doctor shopping” by caregivers seeking treatment for their child. currently there are no fda-approved treatments for molluscum, and treatments utilized may not be appropriate for young patients due to pain or side effects. in the absence of safe and effective treatment options, caregivers may be proactive to help their child get rid of the infection. survey results showed that there was a discrepancy in the percentage of caregivers that were told there were treatment options (79%) vs. those that had the treatments described (61%), suggesting that some hcps may have mentioned treatments were available, but that letting the disease run its course was the best course of action, or that caregivers chose not to use available treatments. skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 369 figure 1. responses to the question: “which of the following ways of dealing with molluscum did you decide on for your child?”* *caregivers may have utilized more than one treatment modality for their child in those caregivers that opted for treatment, many different modalities were utilized including in-office, at-home, and consumer/home remedies, with an average of 2 treatments used by caregivers for their children with molluscum. the use of at-home remedies potentially represents a need by the caregiver to seek a solution if none is offered or if their current hcp-recommended treatments are not meeting expectations for safety, efficacy, or speed of resolution. using unproven consumer or at-home remedies may result in a lack of efficacy, skin reactions, as well as a potential for spread of the disease to other areas of the body or other people.4 the number of caregivers that attempted to squeeze or remove the lesions at home is most concerning, given the contagious nature of the infection and the amount of virus found in lesion material.7 despite most caregivers in the study being warned about the infectious nature of the disease, many reported the spread of molluscum to other caregivers reported an impact of caring for a child with molluscum on their lives as well as their children’s lives, including a limitation of activities their child enjoys. the majority of caregivers expressed concern over social stigma, including worrying about what others thought of their family having a child with molluscum. this research had several limitations. survey respondents were paid and there were requirements on the percentage of genders of caregivers (to ensure accurate representation), the time since the child had molluscum (for recall purposes), as well as skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 370 figure 2. responses to the statement “i worried about what people thought about our family having a child with molluscum” figure 3. the level of impact reported for molluscum on the caregiver’s life (left) and on the child’s life (right) skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 371 requirements of ages of children. the survey questions had not been tested for validity or reliability, and further research is warranted in this area. levels of severity or impact of qol questions were not defined, leaving the parameters up to interpretation by the respondent. in addition, diagnosis of molluscum was based on respondents’ attestation, and only included caregivers’ view of their and their children’s experience with molluscum. these aspects could limit the generalizability of the conclusions. in conclusion, this survey shows that the journey to a diagnosis of molluscum may require seeing several types of hcps, and many patients may not receive the option of treatment or may try more than one option. caregivers may take matters into their own hands to treat their child’s molluscum at home with unproven modalities or by disturbing lesions, which can cause safety concerns or the spread of the infection. there is a clear unmet need for education on diagnosis for hcps and techniques on mitigating the spread of the infection for caregivers. future research using validated measures is needed to further evaluate the impact of the disease and the patient journey toward diagnosis, treatment, and clearance for patients with molluscum and their caregivers. acknowledgements: we express great gratitude for ms. sheila kennedy and her work in formulating the survey questions, and dr. christine crosby for her editing assistance. finally, we thank the respondents of the survey for sharing their experiences with us. conflict of interest disclosures: dr.’s kwong, hebert, and utley have received consulting funds from advisory boards for verrica pharmaceuticals inc. dr. kwong has received research funds for studies unrelated to this survey from verrica pharmaceuticals inc. dr. olivadoti is an employee of verrica pharmaceuticals inc. and receives a salary. funding: funding for the creation and management of the survey and data output was provided by verrica pharmaceuticals inc. to whitman insight strategies. funding was also supplied by verrica pharmaceuticals inc. to versant learning solutions for creation of graphs. corresponding author: melissa olivadoti, phd 44 w gay street suite 400 west chester, pa, 19380 email: medinfo@verrica.com references: 1. shisler jl. immune evasion strategies of molluscum contagiosum virus. adv virus res. 2015;92:201-252. 2. olsen jr, gallacher j, finlay ay et al. time to resolution and effect on quality of life of molluscum contagiosum in children in the uk: a prospective community cohort study. lancet infect dis. 2015;15(2):190-195. 3. silverberg n. pediatric molluscum contagiosum: optimal treatment strategies. paediatr drugs. 2003;5(8):505-512. 4. van der wouden jc, menke j, gajadin s, et al. interventions for cutaneous molluscum contagiosum. cochrane database syst rev. 2006(2):cd004767. 5. hughes cm, damon ik, reynolds mg. understanding u.s. healthcare providers' practices and experiences with molluscum contagiosum. plos one. 2013;8(10):e76948. 6. braue a, ross g, varigos g, kelly h. epidemiology and impact of childhood molluscum contagiosum: a case series and critical review of the literature. pediatr dermatol. 2005;22(4):287294. 7. chen x, anstey av, bugert jj. molluscum contagiosum virus infection. lancet infect dis. 2013;13(10):877-888. conclusion objective covid-19 in tralokinumab-treated patients with moderate-to-severe atopic dermatitis: case series from the ecztend long-term extension trial andrew blauvelt1, andrew pink2, margitta worm3, richard langley4, antonio costanzo5, le gjerum6, emilie jorgensen6, joshua corriveau7, emma guttman-yassky8 • there is special interest in the impact of covid-19 on individuals with chronic immune-mediated diseases such as atopic dermatitis (ad), including concerns that patients treated with immunomodulatory therapies for these diseases may have increased risk of developing covid-19 or more severe disease with worse outcomes following infection with sars-cov-2 • ad is a chronic inflammatory disease,1 characterized by eczematous skin lesions and multiple symptoms, including pruritus, sleep disturbance, and depression2-4 • tralokinumab is a high-affinity, fully human, monoclonal antibody designed to specifically neutralize interleukin-13, a key driver of the underlying inflammation in ad5-7 • phase 3 trials have established the efficacy and safety of tralokinumab for up to 52 weeks in adult patients with moderate-to-severe ad8,9 • an ongoing, open-label extension trial, ecztend (nct03587805), is investigating the long-term safety and efficacy of tralokinumab in patients with ad who participated in previous tralokinumab trials to describe the outcomes of adult patients diagnosed with covid-19 while participating in the tralokinumab long term extension trial, ecztend. 1oregon medical research center, portland, or, usa; 2st. john's institute of dermatology, guy’s and st. thomas’ hospitals, london, uk; 3division of allergy and immunology, department of dermatology, venereology and allergy, charité –universitätsmedizin berlin, berlin, germany; 4division of clinical dermatology and cutaneous science, dalhousie university, halifax, ns, canada; 5dermatology unit department of biomedical sciences, humanitas university, via rita levi montalcini, 20089, pieve emanuele, milano, italy. skin pathology laboratory, humanitas research hospital irccs, via manzoni 56, 20089, rozzano, milano, italy; 6leo pharma a/s, ballerup, denmark; 7leo pharma inc., madison, nj, usa; 8department of dermatology and the immunology institute, icahn school of medicine at mount sinai, new york, ny, usa introduction methods • as shown in figure 1, ecztend is an ongoing, 5 year, open-label, single-arm, multicenter, long-term extension trial in patients with ad who participated in parent tralokinumab trials (ecztra 1-8 and traski)a o approximately 1600 patients with moderate-to-severe ad across canada, the united states, europe, and japan are participating in ecztend o patients received subcutaneous tralokinumab 300 mg q2w plus optional tcs after a 300 mg or 600 mg loading dose of tralokinumab o safety follow-up 16 weeks after last investigational medicinal product • key inclusion criteria for ecztend: o completed treatment period(s) in a tralokinumab parent trial (ecztra 1-8 or traski) without any safety concerns o complied with the clinical trial protocol in the parent trial o able and willing to self-administer tralokinumab, or have it administered by a caregiver, at home after the initial 3 injection visits at trial site o applied a stable dose of emollient (minimum twice daily) for at least 14 days before baseline • here, we report a case series of 51 adult patients with moderate-to-severe ad who had confirmed cases of covid-19 during treatment with tralokinumab every 2 weeks o patients were not required to discontinue tralokinumab treatment following a covid-19 diagnosis, if continuation was deemed appropriate by the investigator o this is an interim analysis of data collected through february 26, 2021 figure 1. ecztend open-label extension trial design. table 1. baseline demographics for patients in ecztend with confirmed cases of covid-19. patient characteristics references disclosures concluding remarks in the present study, covid-19 cases were predominately mild or moderate (96%), and all patients continued tralokinumab treatment following covid-19 diagnosis. • severe covid-19 is characterized by release of pro-inflammatory cytokines, leading to pulmonary inflammation and impairment of lung function • il-13 is not thought to be a major contributor to host defense mechanisms against viral infections • the recent ecztra 5 vaccine study showed that non-live vaccines could be safely administered and can elicit normal immune responses in patients treated with tralokinumab10 1. weidinger s, novak n. lancet. 2016;387:1109–22; 2. eckert l, et al. j am acad dermatol. 2017;77:274–9.e273; 3. silverberg ji, et al. ann allergy asthma immunol. 2018;121:340–7; 4. dalgard fj, et al. j invest dermatol. 2015;135:984–91; 5. bieber t. allergy. 2020;75:54–62; 6. tsoi lc, et al. j invest dermatol. 2019;139:1480–9; 7. popovic b, et al. j mol biol. 2017;429:208–19; 8. wollenberg a, et al. br j dermatol. 2020. doi:10.1111/bjd.19574; 9. silverberg ji, et al. br j dermatol. 2020. doi:10.1111/bjd.19573; 10. merola j, et al. tralokinumab does not impact vaccine-induced immune responses: results from a 30-week, randomized, placebo-controlled trial in adults with moderateto-severe atopic dermatitis. j am acad dermatol. 2021. published online 17 march 2021. doi: 10.1016/j.jaad.2021.03.032 • andrew blauvelt is a scientific adviser and clinical study investigator for abbvie, aclaris, almirall, arena, athenex, boehringer ingelheim, bristol-myers squibb, dermavant, dermira, eli lilly, flx bio, forte, galderma, janssen, leo pharma, novartis, ortho derm, pfizer, regeneron pharmaceuticals, inc., sandoz, sanofi genzyme, sun pharma, ucb pharma, and a paid speaker for abbvie • andrew pink reports personal fees and nonfinancial support from leo pharma, novartis, and ucb; and personal fees from abbvie, almirall, janssen, la roche posay lilly, and sanofi • margitta worm declares that she has receipt honoraria or consultation fees by alk-abelló arzneimittel gmbh, mylan germany gmbh, leo pharma gmbh, sanofi-aventis deutschland gmbh, regeneron pharmaceuticals, inc., dbv technologies s.a, stallergenes gmbh, hal allergie gmbh, allergopharma gmbh & co. kg, bencard allergie gmbh, aimmune therapeutics uk limited, actelion pharmaceuticals deutschland gmbh, novartis ag and biotest ag • richard langley has served and has received compensation in the form of grant funding and/or honoraria as principal investigator for and is on the scientific advisory board or has served as a speaker for abbvie , amgen , boehringer ingelheim , celgene , janssen , leo pharma , eli lilly , merck , novartis , pfizer , sun pharma , and ucb • antonio costanzo has served on advisory boards celgene, ucb, eli lilly, pfizer, janssen, novartis, sanofi-genzyme and msd • le gjerum, emilie jorgensen, and joshua corriveau are employees of leo pharma a/s • emma guttman-yassky has received honoraria for consultant services from abbvie, almirall, amgen, asana biosciences, boerhinger ingelhiem, cara therapeutics, celgene, concert, dbv, dermira, ds biopharma, lilly, emd serono, escalier, galderma, glenmark, kyowa kirin, leo pharma, mitsubishi tanabe, pfizer, rapt therapeutics, regeneron, sanofi, sienna biopharma, and union therapeutics and received research grants for investigator services from abbvie, almirall, amgen, anaptysbio, asana biosciences, boerhinger ingelhiem, celgene, concert, dermavant, dermira, ds biopharma, lilly, glenmark, galderma, innovaderm, janssen, kiniska, kyowa kirin, leo pharma, novan, pfizer, ralexar, regeneron, sienna biopharma, ucb, and union therapeutics acknowledgements • the ecztend clinical trial was sponsored by leo pharma • editorial support was provided by clair geary, phd of alphabet health (new york, ny), supported by leo pharma, according to good publication practice guidelines (https://www.ismpp.org/gpp3) table 3. adverse events details for patients in ecztend with confirmed cases of covid-19. originally presented at revolutionizing atopic dermatitis (rad), june 13, 2021. results covid-19 case series (n=51) age mean (range) 37.7 (19-70) sex male, n (%) 22 (43%) female, n (%) 29 (57%) baseline bmi mean (range) 27.6 (16.3-50.8) geographic region north america, n (%) 15 (29%) europe, n (%) 36 (71%) table 2. clinical characteristics for patients in ecztend with confirmed cases of covid-19. • covid-19 severity was predominantly mild (35/51, 68.6%) or moderate (14/51, 27.5%), and all patients with mild or moderate disease recovered fully (table 3) • the two patients who experienced severe cases (2/51, 3.9%) had multiple risk factors and comorbidities, including obesity, copd, and cardiovascular disease. both were hospitalized and subsequently recovered (one with sequelae); neither case was reported as related to tralokinumab treatment • mean duration of infection was 15 days (range 1-39 days) • only two of the 51 covid-19 cases were reported as possibly related to tralokinumab treatment; both were mild or moderate cases occurring in patients under the age of 30 • all (51/51) patients continued tralokinumab treatment, the majority (38/51, 75%) without dose interruptions following covid-19 diagnosis • regarding comorbidities that confer additional risk of severe covid-19, 59% (n/n, 30/51) of patients had asthma and 10% (5/51) had hypertension; cardiovascular disease was present in 2 patients and chronic obstructive pulmonary disease (copd) and diabetes mellitus were present in 1 patient each (table 2) • in the ecztend study, 19 patients have received the first dose of covid-19 vaccine and 6 patients have received the second dose; no patients had adverse events leading to permanent discontinuation after receiving the vaccine as per data cut-off site visit. iga, easi, scorad, worst weekly pruritus nrs, eczemarelated sleep nrs, use of topical treatment screening and follow-up visits home use training poem, dlqi / cdlqi, eq-5d-5lc antidrug antibody / pharmacokinetic measurement weeks from first treatment in ecztend 5640322416 484 8–2 0 screening period tcs use allowed visit schedule until end of may 2021b 248 • twenty-two male and 29 female patients were diagnosed with covid-19 through february 2021 (table 1) • the mean age was 37.7 years (range 19-70 years) and the mean bmi was 27.6 (range 16.3-50.8) covid-19 case series (n=51) pye tralokinumab (parent trial + ecztend) mean 2.3 history of: diabetes mellitus, n (%) 1 (2%) cardiovascular disease, n (%) 2 (4%) hypertension, n (%) 5 (10%) copd, n (%) 1 (2%) asthma, n (%) 30 (59%) covid-19 case series (n=51) disease duration in days mean (range) 15.2 (1-39) disease course mild, n (%) 35 (69%) moderate, n (%) 14 (27%) severe, n (%) 2 (4%) hospitalizations n (%) 2 (4%) mean duration of stay (range) 7 (5-9) possibly related to treatment n (%) 2 (4%) recovery full, n (%) 50 (98%) with sequelae, n (%) 1 (2%) not recovered, n (%) 0 tralokinumab continuation no dose interruption, n (%) 38 (75%) dose interruption, n (%) 13 (25%) aprevious treatment regimens in parent trials included tralokinumab q2w, q4w, or placebo +/tcs bafter may 2021, some site visits will be switched to telephone visits. bpatients from the parent trial ecztra 6 will not perform the eq5d-5l. cdlqi, children’s dermatology life quality index; dlqi, dermatology life quality index; easi, eczema area and severity index; eq5d-5l, euroqol 5 dimension health questionnaire 5-level; iga, investigator’s global assessment; nrs, numeric rating scale; poem, patient-oriented eczema measure; q2w, every 2 weeks; scorad, scoring atopic dermatitis; tcs, topical corticosteroid. skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 73 short communication a new skin-colored nodule in a patient with cushing’s disease margaret m appiah, bs1, laurel ball, bs1, ogechi ikediobi, md, phd2, brianne daniels, do2 1 university of california san diego school of medicine 2 university of california san diego, department of dermatology a 26-year-old woman with newly diagnosed eosinophilic granulomatosis with polyangiitis and a recent history of steroidinduced cushing’s disease, as evidenced by an 18 kilogram weight gain, moon facies, scattered ecchymoses, and new-onset stage i hypertension, presented with a newly found growth on the back. she denied trauma, itching, pain, or discharge. there was no personal or family history of melanoma or non-melanoma skin cancer. physical examination revealed a single 6mm pink nodule of the left paraspinal mid-back (figure 1) with no other cutaneous findings. excisional biopsy specimens were obtained (figure 1). initial review of the histology showed fascicles of epithelioid and fusiform cells with abundant cytoplasm in a background mucinous stroma. immunohistologic examination showed ema positivity around the theques as well as positivity for s-100, sox-10, mitf, hmb-45 and nki-c3. stains for ae1/ae3 cytokeratin, p40, chromogranin a, gfap, cd68, smooth muscle actin and cd57 were negative. after excision of the initial nodule, a second similar nodule appeared eight months later, which was excised. the patient was subsequently tapered off of corticosteroid therapy and has had no further recurrence for over two years. this lesion’s positive immunoreactivity with melanoma markers along with its low ki-67 proliferation profile and positive ema reactivity surrounding tumor theques indicate both melanocytic and nerve sheath differentiation1(figure 2). these two distinct staining patterns combined with the histologic findings lead to a final diagnosis of melanocytic schwannoma, first described by carney in 19902,3. the terminology “melanotic schwannoma” and “melanocytic schwannoma” can be found variably throughout the literature. however, some authors suggest the utilization of melanotic schwannoma for schwannomas that produce melanin pigment, and melanocytic schwannoma for those that are amelanotic, but that demonstrate both schwannian and melanocytic lineage2. in this case, the tumor did not produce melanin pigment and did show evidence of schwannian and melanocytic differentiation. as such, the term melanocytic schwannoma will be used to describe this case. melanocytic schwannoma is an extremely rare tumor and dermal presentations are even more rare. to date, less than 20 primary cutaneous or subcutaneous tumors have been reported in the literature1. these tumors may arrive sporadically or in the setting of the carney complex4, which involves mutations in the prkar1a gene and associated endocrinopathies, cutaneous and cardiac myxomas, and additional cutaneous findings skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 74 figure 1. a) melanocytic schwannoma clinical photo b) h&e stain at 10x power figure 2. a) ki-67 staining at 10x b). ema staining at 10x such as lentigines and blue nevi3. in carney’s identification of seventeen patients diagnosed with melanotic schwannomas, nine patients also had a diagnosis of cushing’s 3. our patient exhibited no additional findings of the carney complex, however in light of this observation, it is possible that there is a correlation between her iatrogenic cushing’s through high dose exogenous corticosteroid immunosuppressive therapy and her development of a cutaneous melanocytic schwannoma; however, this remains to be clarified in further studies. melanocytic schwannomas are rare tumors, and their clinical courses are uncertain. additionally, they may mimic other cutaneous lesions and be difficult to distinguish on pathology. therefore, complete excision is recommended, along with possible genetic analysis for diagnostic confirmation 4,5. conflict of interest disclosures: none funding: none a b a b skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 75 acknowledgements we would like to thank the following dermatopathologists for their help in facilitating the preparation of this manuscript: dr timothy mccalmont, dr reza simon jacob, dr cora humberson. corresponding author: brianne daniels do 8899 university center lane suite 350 san diego, ca 92122 email: bdaniels@health.ucsd.edu references: 1. effah, k, seidl,s, gorges, e, akakpo, pk. melanotic schwannoma of the vagina: a report of a very rare tumor and review of the literature. case rep obstet gynecol. 2019 jun 17;2019:8521834. doi: 10.1155/2019/8521834. ecollection 201 2. yeh, i, argenyi, z, vemula, ss, furmancyzk, ps, bouffard, d, mccalmont, th. plexiforma melanocytic schwannoma: a mimic of melanoma. j cutan pathol. 2012 may;39(5):521-5. doi: 10.1111/j.16000560.2011.01856.x. epub 2012 mar 15. 3. carney, j. psammomatous melanotic schwannoma. a distinctive, heritable tumor with special associations, including cardiac myxoma and the cushing syndrome. am j surg pathol. 1990 mar;14(3):206-22. 4. cohen jn, yeh i, leboit pe. melanotic schwannoma of the vulva: a case report and review of the literature. am j dermatopathol. 2020 jan;42(1):46-51. doi: 10.1097/dad.0000000000001482. pmid: 31268928. 5. kaehler, kc, russo, paj, katenkamp, d, et al. melanocytic schwannoma of the cutaneous and subcutaneous tissues: three cases and a review of the literature. melanoma res. 2008 dec;18(6):438-42. doi:10.1097/cmr.0b013e32831270d7 mailto:bdaniels@health.ucsd.edu https://www.ncbi.nlm.nih.gov/pubmed/2305928 https://www.ncbi.nlm.nih.gov/pubmed/2305928 https://www.ncbi.nlm.nih.gov/pubmed/2305928 methods • excised human abdominal skin tissue samples of 500-µm thickness were pretreated with a low-power 1440-nm fractional diode laser (clear + brilliant® laser system; solta medical, bothell, wa) using either 80 or 320 microscopic treatment zones (mtz)/cm2, or received no laser pretreatment (table 1) table 1. experimental parameters • following laser pretreatment, 2% salicylic acid was applied, and uptake was determined at various time points up to 24 hours after application (figure 1) figure 1. study design for testing uptake of topicals on skin tissue. pbs, phosphate-buffered saline. • samples were filtered and analyzed using high-performance liquid chromatography to obtain permeation and retention for laser-treated samples and untreated controls • total uptake was calculated as the sum of the normalized cumulative permeation and retention in each sample • average total uptake was compared between laser-treated samples and untreated controls to determine the uptake enhancement ratio results • cumulative permeation of 2% salicylic acid at 24 hours posttreatment was similar for both 1440-nm pretreatments (80 and 320 mtz/cm2; both 0.01 mg/cm2) and untreated control (0.009 mg/cm2; figure 2) figure 2. cumulative permeation of 2% salicylic acid through 24 hours after 1440-nm laser pretreatment. values are mean ± standard deviation. mtz, microscopic treatment zones. • retention of 2% salicylic acid was ~9 times greater with 320-mtz/cm2 pretreatment compared to both 80-mtz/cm2 pretreatment and untreated control (table 2) table 2. enhancement of 2% salicylic acid retention synopsis • the structure of the stratum corneum can limit uptake and effectiveness of topical medications1; however, lasers can disrupt the stratum corneum and tight junctions in the epidermis, allowing for better topical penetration and absorption2 • non-ablative fractional lasers have less effect on the stratum corneum, can minimize thermal side effects, and can shorten postprocedural downtime compared to ablative lasers3,4 • the relationship between topical uptake and laser device settings, such as wavelength, peak power, and spot density, must be quantified to optimize treatments enhanced uptake of 2% salicylic acid following 1440-nm non-ablative fractional diode laser treatment jordan v. wang, md, mbe, mba1; paul m. friedman, md1,2; adarsh konda, pharmd3; catherine parker, np, msn4; roy g. geronemus, md1 1laser & skin surgery center of new york, new york, ny; 2dermatology and laser surgery center, houston, tx; 3bausch health us, llc, bridgewater, nj; 4solta medical, bothell, wa objective • to quantify uptake of topical 2% salicylic acid after pretreatment with a 1440-nm non-ablative fractional diode laser with varying treatment densities conclusions • in this ex vivo analysis of transdermal 2% salicylic acid uptake, low-power 1440-nm non-ablative fractional diode laser pretreatment with 320 mtz/cm2 resulted in greater retention within skin tissue samples compared to untreated controls and the 80-mtz/cm2 setting • retention enhancement following treatment with greater mtz density did not appear to have an additive effect on overall uptake at 24 hours, supporting the argument that salicylic acid uptake may be predominantly transfollicular • these results may guide the development of treatment protocols for clinical use of non-ablative fractional laser pretreatment to enhance uptake of salicylic acid–containing topicals presented at the 2021 fall clinical dermatology conference • october 21-24, 2021 • las vegas, nv, and virtual funding information: this study was sponsored by solta medical. medical writing support was provided by medthink scicom and funded by solta medical. disclosures: jvw is an investigator for solta medical. pmf serves on the advisory board and speaker bureau for solta medical. ak and cp are employees of and may hold stock or stock options in solta medical. rgg is an investigator and advisory board member for solta medical. references: 1. lee et al. eur j pharm sci. 2016;92:1-10. 2. machado et al. aesthetic plast surg. 2021;45:1020-1032. 3. friedman et al. j drugs dermatol. 2020;19:s3-s11. 4. farkas et al. aesthet surg j. 2013;33:1059-1064. parameter setting device wavelength, nm 1440 1440 spot density, mtz/cm2 80 320 peak power, w 1.2 3 spot size, µm 130 130 pulse energy, mj 9 9 mtz, microscopic treatment zones. 80 mtz/cm2 320 mtz/cm2 control 1.06 ± 0.40 x 9.31 ± 3.96 x 80 mtz/cm2 — 8.74 ± 3.60 x mtz, microscopic treatment zones. figure 1 sample & refill 500-µm skin graft topical formulation pbs solution w/ 0.2% sodium azide donor chamber permeation/diffusion chamber stir bar stir rotation figure 2 0.009 0.010 0.010 0 0.002 0.004 0.006 0.008 0.01 0.012 0.014 0 5 10 15 20 25 30 c um ul at iv e pe rm ea ti o n, m g/ cm 2 time, hours control kovar-1435nm tuscany-1435nm control 80 mtz/cm2 320 mtz/cm2 skin july scom 1264 proof returned skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 445 short communication facial pyoderma gangrenosum: overcoming anchoring bias andrew c. whittington1, do, ross pearlman, md2, robert t. brodell, md2 1 department of medical education, corpus christi medical center, corpus christi, tx 2 department of dermatology, university of mississippi medical center, jackson, ms pyoderma gangrenosum (pg) is a rare, noninfectious, ulcerating disease that commonly affects women between 40 to 60 years of age. it usually occurs on the lower extremities; however, it can occur anywhere.1 a case of recurrent pg in a 44-year-old female is presented to highlight the difficulty in making this diagnosis on the face. a 44-year-old woman presented with a 2week history of a 4 x 5 cm beefy-red ulceration on the left chin (figure 1). one year earlier, a small red papule developed on her right upper lip that enlarged into an angulated ulceration over 2-3 weeks. the patient admitted to “rubbing” the lesion but denied “picking.” a 4 mm punch biopsy from the edge of the ulcer demonstrated acute on chronic inflammation and fibrosis. within weeks, a new 2 x 2 cm ulceration developed on the right medial eyebrow. a diagnosis of factitial dermatitis was made. over a oneyear period, there was little improvement in these lesions despite treatment with topical antibiotics, petroleum jelly, honey with collagen powder, and a variety of dressings. the patient was urged to avoid “picking” at the lesions. about 14 months after her initial visit, she returned to clinic reporting spontaneous resolution of the lip and eyebrow ulcers. she had undergone spinal surgery 6 weeks prior figure 1. to this visit receiving several doses of intravenous corticosteroids following the procedure with resolution of all facial ulcers in one month. one new ulcer developed on the left chin in the previous two weeks which she attributed to irritation from a post-operative supportive neck brace. at this point, a past medical history of inflammatory bowel disease was ascertained (ibd). given the improvement associated with intravenous corticosteroids and newly discovered history of ibd, the diagnosis was revised to pg. treatment with oral prednisone 60 mg tapered over 4 weeks, intralesional triamcinolone, and petroleum jelly led to flattening of the rolled border and skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 446 table 1. comparison of facial ulcerations in factitial disease versus pyoderma gangrenosum characteristics factitial ulcerations pyoderma gangrenosum associated conditions anxiety and psychiatric conditions inflammatory bowel disease, inflammatory arthritis & hematologic disorders relationship to trauma persistent trauma potentiates ulcerations trauma initiates ulcerations (pathergy) appearance angulated borders rolled borders pathology non-specific findings non-specific findings treatment covering wounds to avoid continuing trauma/psychotherapy and psychopharmacology oral or intralesional steroids then complete clearance of ulcers in 1 month. pg is a rare ulcerating neutrophilic dermatosis.1 the pathophysiologic basis is poorly understood, but it may result from a combination of neutrophil dysfunction, inflammatory mediators, and genetic predisposition. pg is associated with underlying medical conditions such as ibd, inflammatory arthritis, or hematologic disorders.2 while it most commonly affects the lower limbs, pg can involve any area of the body. head and neck involvement is, however, rare.3 since there are no diagnostic, serologic or histologic features, pg is diagnosed based on the clinical findings. the presence of associated diseases, such as ibd, are important clues. factitial disease is a particularly difficult diagnosis to exclude4 (table 1). in this case, the patient’s description of “rubbing” was believed to be an admission of “picking,” erroneously contributing to our error in diagnosis. in addition, the rarity of pg on the face inappropriately led to the exclusion of this consideration. diagnostic momentum was responsible for an unwavering diagnostic conviction for almost a year, during which time the ulcerations did not improve.5-6 clinicians should remain wary of complicating biases that distort their view of the clinical picture. abbreviations used: pg: pyoderma gangrenosum; ibd: inflammatory bowel disease conflict of interest disclosures: robert t. brodell discloses the following: multicenter clinical trials: novartis – principal investigator; corona psoriasis biologic registry. editorial boards: faculty advisor, american medical student research journal; editorin-chief, practice update dermatology; associate editor, journal of the american academy of dermatology; practical dermatology; journal of the mississippi state medical society; skin: the journal of cutaneous medicine; archives of dermatological research. advisory boards: bracco diagnostics, inc. (gadolinium-based contrast agent litigation); chairperson of regn3500 ad independent skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 447 monitoring committee (idmc) (sanofi genzyme/regeneron); sunpharma; and, cassiopea. dr whittington has no conflicts of interest to disclose. funding: none corresponding author: robert t. brodell, md university of mississippi medical center 2500 north state street jackson, mississippi 39216 phone: 330-393-4000 fax: 330-392-5870 email: rbrodell@umc.edu references: 1. ahronowitz i, harp j, shinkai k. etiology and management of pyoderma gangrenosum. american journal of clinical dermatology. 2012; 13: 191-211. 2. braswell sf, kostopoulos tc, ortega-loayza, ag. pathophysiology of pyoderma gangrenosum (pg): an updated review. journal of the american academy of dermatology. 2015; 73 (4): 691-698. 3. binus am, qureshi aa, li vw, winterfield ls. pyoderma gangrenosum: a retrospective review of patient characteristics, comorbidities and therapy in 103 patients. british journal of dermatology. 2011;165(6):1244-50 4. lavery mj, stull c, mccaw i, anolik rb. dermatitis artefacta. clinics in dermatology, 36 (6): 719-722. 5. lowenstein ej. dermatology and its unique diagnostic heuristics. journal of the american academy of dermatology. 2018; 78 (6): 12391240. 6. helms se and brodell rt. let’s acknowledge our mistakes and learn from them! british journal of dermatology. 2018; 179 (6): 1237-1239. skin july 2021 1316 proof skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 372 original research an economic evaluation of the budget impact of precision medicine testing for the treatment of psoriasis jashin j. wu md, faad1, paul w. montgomery iii, ms2, blake long md, mba3, tobin j. dickerson, phd2, margaret l. snyder, md4, martyn gross, mba2, lena chaihorsky, bs3, hannah mamuszka, ms3, mike fried mba, mhi3 1dermatology research and education foundation, irvine, ca 2mindera corporation, san diego, ca 3alva10, cambridge, ma 4department of dermatology, icahn school of medicine at mount sinai, 5 east 98th street, 5th floor, new york, ny plaque psoriasis is a t-cell mediated, inflammatory skin disease which affects approximately 2.8% (~7.5 million people) of the united states (u.s.) population. cutaneous lesions are often associated with marked pruritic and burning sensations. these symptoms are frequently accompanied by a significant cosmetic concern for patients, leading to a sizable impact on their overall quality of life. furthermore, psoriasis is positively associated with the presence of cardiovascular, psychiatric, and other abstract background: this study was a budget impact analysis based on a budget impact model (bim) and formularies from different commercial payer types (excluding medicare and medicaid). the primary objective of this study was to determine the potential cost savings utilizing precision medicine testing of biologics in patients with psoriasis. the evaluation projects the predicted cost savings of multiple formulary scenarios, simulated through the bim. methods: a budget impact model was constructed to simulate the impact of mind.px, a transcriptomic predictive precision medicine test that can discriminate between psoriasis responders and nonresponders, on psoriasis drug usage. this model simulated the impact of mind.px on different formularies and cost scenarios, considering the efficacy of individual biologics. all formularies used were acquired from the policy reporter database. results: several payers representing a spectrum of covered lives populations were used to simulate the impact of mind.px through the budget impact model. the budget impact model returned cost savings as low as $5,138 annually to as high as $13,141 annually. based on the analysis of this subset of payers, the model yielded average cost savings of $8,492 annually as well as an average wasted spend savings of $16,567. all savings are represented on an annual per patient basis. conclusions: these savings demonstrate the potential cost savings that precision medicine testing can provide to ease the economic burden on payers, clinics/hospital systems, and patients, and may fill the need for a better method to prescribe drugs for the treatment of psoriasis. introduction skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 373 medical comorbidities, and is therefore considered the second largest contributor of skin-related disabilities.1 in fact, psoriasis has been recognized as a serious noncommunicable disease by the world health organization (who) since 2014, with estimates that total disability-adjusted life years (dalys) due to this auto-inflammatory condition have doubled from 0.1% in 1990 to 0.2% in 2017.1-3 this effect is due in part to incorrect or delayed diagnosis, inadequate treatment, insufficient access to care, and social stigmatization.2 in order to reduce the physical, psychological, and economic burden, it is imperative that physicians quickly identify a safe and effective treatment regimen for those suffering with this chronic skin condition. in recent decades, remarkable advancements in targeted biologic immunotherapy have revolutionized the treatment of psoriasis via the development of a multitude of novel systemic agents. these therapeutic monoclonal antibodies are highly specific immuno-modulators which are proven to be exceptionally effective in the clearance of skin lesions. due to the inhibition of unique, distinct points along the inflammatory cascade (e.g., il-17 vs il-23 blockade, etc), biologics are not a one-sizefits-all treatment. in other words, the agent most efficacious for one patient may differ from the option that is most suitable for someone else, supporting the need for an individualized therapeutic approach. unfortunately, there are currently limited resources for healthcare providers to discriminate between the plethora of available systemic agents when deciding on treatment for a particular patient. therefore, many patients try multiple medications before finding the best fit for them, leading to significant morbidity and economic burden. in fact, medication alone can cost up to $366,645 per patient annually in order to achieve a psoriasis area and severity index score (pasi) 100 response, or complete clearance of skin lesions.4 this leads to an estimated direct cost of $12.2 billion united states dollars (usd; all costs are reported in usd) and estimated indirect cost of $23 billion.5,6 in the u.s. alone, it is estimated that patients with psoriasis will pay a lifetime cost of $11,498 for relief of physical and emotional symptoms, resulting in an annual national cost of an estimated $112 billion to treat these patients.7 this expense is expected to increase as the prevalence of psoriasis continues to rise, highlighting the need for expedited identification of an agent with a robust and long-lasting clinical response for a given individual. interestingly, factors such as a person’s genomic profile may provide clues into their particular disease pathophysiology and, consequently, offer insight into the most effectual treatment option for them. this precision medicine testing has demonstrated clinical validity and utility across many indications and has been shown to ease the economic burden of treatment by minimizing wasted-spend and increasing netsavings.3,8,9 to date, a validated precision medicine test for predicting response to drugs for psoriasis does not exist. this study aims to simulate and predict the cost savings of congruent use of precision medicine testing for the biologic treatment of psoriasis in a world with mind.px. for the purposes of this work, congruent use is defined as using a biologic treatment as predicted for best response by the precision medicine test results. mind.px mind.px is a precision medicine test that has been developed by mindera (san diego, ca) that uses a proprietary minimally invasive dermal biomarker patch (dbp) to extract rna from skin. the dbp specifically extracts mrna from the epidermis and dermis of patients, which can then be analysed by nextgeneration sequencing (ngs). the resulting skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 374 transcriptomic data is then processed by algorithms derived using machine learning and generates a report that provides information about potential patient response to drug class to clinicians. model design this model estimates the potential budget impact of the mind.px precision medicine test by using a decision-tree budget impact model (bim) for patients in the treatment of moderate-to-severe psoriasis. the bim was developed using microsoft excel 2016 to compare the drug costs of today’s standard of care (soc) vs. a future state with a new precision medicine test. the model was constructed from a u.s. healthcare commercial payer perspective (excluding medicare and medicaid) and the drug treatment costs are measured over a oneyear period in 2020 usd.11 model inputs individual drug performance the model evaluated various payer formulary scenarios based on 14 available psoriasis biologics spread across three drug classes (tnfα-inhibitor, il-17’s, and il-23’s) (table 1). each of the 14 drugs were given an associated wholesale acquisition cost (wac) price per dose, wac price per loading dose week, wac price per maintenance dose week, response rate and rate of being prescribed relative to the 14 available drugs. food and drug agency (fda) package inserts were used to determine the count of loading doses per week, maintenance doses per week, and total weeks on a loading dose which were used to determine the average loading and maintenance costs per week. usage rates12 represent the prescribing patterns between the 14 drugs and were used to determine the relative weighting of each drug within a drug class based on the baseline formulary. the response rate used both two methodologies, fda label package inserts and real-world data class averages.39 the fda label package inserts, an average was used of drug pasi 75 and physician global assessment (pga) or investigators global assessment (iga) efficacy. drug class performance the model creates an aggregated drug class view based on the individual drugs chosen in the formulary and weighted based on the industry usage rates for each of the 14 drugs relative to each other. rather than account for each possible drug formulary combination, the model converted individual drugs in the baseline formulary to class averages and weighted based on usage prescribing rates. each class has a calculated percent of patients assigned to each drug class, the average fda label drug response rate, real-world data drug response rate, average loading dose cost, and average maintenance dose cost. all results in this research uses the real-world data drug class average of 46.0% for tnfα, 55.9% il-17’s and 50.7% for il-23’s.39 exceptions are noted when modelling against fda label package drug response rates. while costs are based on wac, the model applied a discount percent to emulate true payer costs. tumour necrosis factor (tnfα) inhibitors were assigned a discount rate of 28%, interleukin-17 (il-17) inhibitors 38%, and interleukin-23 (il-23) inhibitors a rate of 49% respectively (table s1).39 the secondary response rate was reduced and compared to the primary response rate to account for the reduced efficacy experienced when a patient cycles from one drug in a drug class to a different drug within the same methods skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 375 table 1. characterization of drugs of interest [13-27]. per week loading costs – total start-up drug costs divided by weeks in start-up. per week maintenance costs – price per dose multiplied by average doses per week during maintenance period. response rate – average of drug pasi 75 and pga or iga efficacy. usage rate – displays the relative percent use of each drug used in this model in the treatment of mild to severe psoriasis based on the drg [12] report. usage rate is an average between 2018 reported usage rates and 2028 forecast usage rates to account for future trends drug class drug (brand name) price per dose wac per week loading costs per week maintenance cost response rate usage rate tnfα inhibitor certolizumab pegol (cimzia) $2,315 $2,315 $1,158 65.3% 1.5% tnfα inhibitor etanercept (enbrel) $1,389 $2,778 $1,389 36.6% 10.0% tnfα inhibitor etanercept-szzs (erelzi) $1,388 $2,776 $1,388 36.6% tnfα inhibitor adalimumab (humira) $2,745 $5,490 $1,372 65.3% 17.4% tnfα inhibitor infliximab-dyyb (inflectra) $936 $468 $117 75.9% tnfα inhibitor infliximab (remicade) $1,160 $580 $145 75.9% 2.6% tnfα inhibitor infliximab-adba (renflexis) $746 $373 $93 75.9% il-17 inhibitor secukinumab (cosentyx) $5,477 $5,477 $1,369 65.9% 14.6% il-17 inhibitor brodalumab (siliq) $1,221 $1,221 $611 82.0% 0.5% il-17 inhibitor ixekizumab (taltz) $5,690 $2,845 $1,423 85.2% 11.5% il-23 inhibitor tildrakizumabasmn (ilumya) $14,537 $7,268 $1,211 59.4% 2.3% il-23 inhibitor risankizumabrzaa (skyrizi) $12,974 $12,974 $1,081 87.0% 7.7% il-23 inhibitor ustekinumab (stelara) $22,777 $11,38 $1,898 80.0% 15.1% il-23 inhibitor guselkumab (tremfya) $11,245 $5,623 $1,406 78.4% 9.2% skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 376 class. as a result, a reduction was applied to the response rates and assumes a 50% drop for tnfα inhibitors, and a 75% drop for il-17 inhibitors and il-23 inhibitors, respectively (table s1).33 the reduced drug efficacy rates were applied in the model whenever a patient does not respond to a drug in a particular drug class but is forced by the confines of the formulary to be assigned a different drug within the same drug class. payer drug formulary of the 14 drug options, a baseline payer formulary was chosen consisting of a tier 1 and tier 2 (scenario c; figure s1). the baseline formulary was then converted to class metrics based on the industry usage patterns of each individual drug chosen. six formulary scenarios were modelled based on different variations of the three drug classes. the baseline formula scenario c (figure s1) was chosen as this closely emulates the average savings across all six scenarios. model logic drug cycling with the model class inputs determined, the baseline scenario is fed into a one-year drug cycling model with 4 equal 13-week time periods. it is assumed all patients are continuously on a drug for the 4 cycles and non-responder patients within a cycle must complete the 13-week cycle before switching to a new drug for the next cycle (figure 1). each cycle is defined as either a loading dose period or a maintenance dose period. the loading dose period includes the costs of the weeks required for the loading dose plus the maintenance weekly costs for any remaining weeks in the 13-week cycle. the maintenance period costs include only maintenance dosing during the 13-week cycle. in the soc base case scenario, based on the calculated class averages, 32% of patients will start cycle 1 on a tnfα-inhibitor, and those patients will have a response rate of 46% (table 2) with a cycle drug costs of $15,811 (table 2). loading dose period costs are applied in cycle 1 as all patients are on a new drug. responder patients will continue the same drug class for the remainder of the model with the application of maintenance period costs. the non-responders will then be cycled to a new drug class or new drug within the same class based on both the formulary and calculated probabilities of usage (figure 2). a patient must cycle through all tier 1 drugs before switching to tier 2 drug options. costs were represented as four 13-week cycle costs that include both drug loading periods and maintenance periods (table 2). future state cycling the objective of this model is to show the economic impact of stratifying patients to the right drug with a high probability of response. therefore, the drug response rates in cycle 1 are assumed to be a baseline of 91% for the initial 13-week period as it is assumed the right patients are placed on the right drug. for cycle 2, it is assumed the responders will remain on the same drug class for the full year, the same methodology as soc. nonresponders, however, will stay on the same drug class as the cycle 1 future state but will be prescribed a different drug. skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 377 figure 1. schematic of drug cycling this is because the mind.px precision medicine test would have guided the clinician to a specific drug class and therefore it is assumed the clinician will try another drug within the same drug class in the second cycle. table 2. baseline aggregated characteristics of drug classes for tier 1 drug cycling. 13-week loading costs shows weighted total costs of drug loading period plus maintenance costs for any remaining weeks up to the 13week mark. 13-week maintenance costs shows the weighted total maintenance cost for a 13-week period. response rate – real world data39. secondary response rate – average drug class response rate when a second drug is used in the same drug class after the first drug failed. drug class 13week load costs 13-week maint. costs response rate39 secondary response rate patient mix percent tnfa inhibitor $15,81 1 $12,846 46% 23% 32% il-17 inhibitor $23,38 5 $10,857 56% 14% 27% il-23 inhibitor $27,66 7 $10,431 51% 13% 42% with the assumption of a 91% sensitivity for the mind.px precision medicine test, the 91% non-response rate in cycle 1 may be a false indication in the test and therefore the patient after a second try with the same drug class will not respond. the response rate for cycle 2 in the future state is 0%. for cycle 3 and 4, assuming non-response to cycle 1 and 2, the patient will then be switched to a new drug class with response rates equal to tier 1 soc baseline drug class averages. the future represents the stratification of patients to the correct biologic treatment prior to entering the model. in the future state, the distribution of patients for cycle 1 drug classes are model inputs and sensitized for a range of results. the baseline assumes 50% of patients in the future state will use tnfα inhibitors and 25% will be placed on an il-17 inhibitor and 25% on il23 inhibitor (table s1). drug costs for the future state are the same for soc. model output the model quantifies the annualized prescription drug and medical cost change by showing the net cost savings created on an average per patient basis. in addition to this metric, wasted spend savings is calculated to show the savings related to drug and medical costs for non-responder patients.34 wasted spend savings is the difference in total medical and pharmacy costs spent on nonresponders currently as compared with a future state with the diagnostic; it is captured by reducing the non-responders in the future state. this metric highlights the ineffective spend dollars that were previously used on skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 378 patients who did not respond to their empirically assigned biologic. figure 2. patient flow diagram budget impact analysis the model predicts that formularies with only adalimumab as a biologic option for tier 1 treatments will have a net cost savings of $5,607 with congruent use of the mind.px precision medicine test annually (scenario a; figure s1). it is noteworthy that as more drugs are introduced into a given formulary, an increase in cost savings can be seen. increase in drug mix in the first tier of the sample scenarios resulted in a net cost savings range of $5,138 $13,141 annually with congruent use of the mind.px precision medicine test (scenarios b-f; figure s1). the average cost savings based on scenarios a-f resulted in $8,492 annually (figure s2). this analysis also predicts high annual wasted spend savings, ranging from $14,330-$22,909 (figure s4). cumulative drug response when analysing the cumulative drug response rates by cycles, it is evident that while full year response rates are nearly the same, the bim predicts that patients who are treated initially with the correct drug (cycles 1-2, figure 3) experience improved outcomes and treatment savings (91% for the future model versus 75.2% for soc). albeit small, improved outcomes and savings can even be seen between cycles 2 and 3 (figure 3). sensitivity analysis one way sensitivity analysis of net savings by formulary scenario compared to the baseline average of $8,492 (scenario c) identified the tier 1 drug mix as the most influential parameter (figure s3). formulary scenarios with a balanced drug mix that favoured il-23 inhibitors usually exceeded the baseline as exemplified by scenario f with 63% il-23 increasing the net savings by $4,649 (figure s3). additional one-way sensitivity analysis of input values compared to the baseline results skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 379 figure 3. cumulative biologic response rate by cycles for soc and the future state average of scenarios a-f was conducted and is presented in the tornado diagram (figure 4). from this analysis, compared to the average savings of $8,492 across scenarios a-f; (figure s3), the next most influential uncertainty parameter affecting net savings is the drug discount from the baseline applied discount off wac, with a 20% decrease in the discount (less of a discount) resulting in an additional net savings of $2,085 (figure 4). varying the future class mix from the baseline (50% tnfi, 25% il-17, 25% il-23) had less of an impact on net savings, with an increase of tnfi use to 60% resulting in increased savings of $594 above baseline average (figure 4). this is supported in the savings in each scenario (figure s2). net savings are also sensitive to changes in the future response rate of being placed on the correct drug as predicted by mind.px. more cost savings are seen as the accuracy of testing is increased. for this analysis, the test accuracy is set at the reported 91%. savings fall below baseline when the testing accuracy is set to 85% and exceeds baseline at both 95% and 100%. response rates based on fda package inserts rather than real world data, yielded net cost savings of $4,016 and wasted spend savings of $6,383. the baseline scenario c response rates for fda package inserts was 65% tnfα inhibitors, 66% for il-17 inhibitor and 80% for il-23 inhibitors compared to 46%, 56% and 51% for real world data respectively (table s2). skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 380 figure 4. tornado diagram showing the most sensitive inputs of the bim. drug discount one-way sensitivity varies the baseline drug discount as used against wac pricing. future response rate is equal to the mind.px test accuracy. future class mix shows the mix ratio of the 3 drug classes in a future state. drug efficacy is the reduced drug class response rate when a second drug is used in the same drug class after the first drug failed. this analysis is the first to estimate the hypothetical economic impact of a precision medicine test for the use of prescribing a biologic treatment for psoriasis. savings and wasted spend the annual net savings with the use of the test is substantial and predominantly formulary driven based on the structure and variability of the selected formulary averaging $8,492 across all 6 formularies. wasted spend however, is not directly affected by the selected formulary but rather is driven by patients being put on the correct treatment initially. net savings and wasted spend are also somewhat influenced by the drug costs, as there is wide variability in payor wac. with an average wasted spend savings of $16,567 among all 6 formularies, these predictions show strong implications of decreased wasted spend applied to any formulary, including those with a low drug mix. net savings were also sensitive to the future response rates. when the test accuracy is decreased, we see lower response rates and thus lower savings. this further supports the need for precision medicine testing (with high accuracy) to identify the right drug for the right patient to increase response rate and increase savings versus the “trial and error” standard of care approach. the model also showed some sensitivity to the future drug class mix. as the future drug class mix of the formularies became more varied, the model trended towards the lower end of savings. this could be due to the fact that with the use of precision medicine testing, inexpensive discussion skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 381 biologics such as tnfα inhibitors are expected to be utilized more than they currently are without the use of precision medicine testing. currently, il-17 and il-23 biologics are used more often than tnfα inhibitors due to their perceived efficacy rates. these classes of biologic are more costly and are not always an effective treatment for all patients. sensitivity analysis of the wasted spend savings by scenario with a set baseline of $16,567 (the average wasted spend savings of scenarios a-f; figure s4) yielded similar results. in addition, utilizing the higher response drug response rates listed in the fda approvals rather than reported real world data still demonstrates significant savings. clinical impact dermatologists are aware of the high annual costs of drugs to psoriasis patients and payers.35,36 studies have shown the increased costs of switching, which may occur within the first 3-6 months of a new drug due to primary failure.36 these initial 36 months overlap with the more expensive loading dose period of most drugs. the clinician value derived from the test may potentially reduce unnecessary switches in the first 3-6 months due to primary failure and prevent multiple loading doses of different drugs in a relatively short time period. the mind.px precision medicine test may also reduce the risk of anti-drug antibodies against the failed drugs. once the immune system ‘sees’ a drug and then it is stopped, anti-drug antibodies are often produced against these drugs. if for some reason the patient is prescribed these biologics again in the future, these anti-drug antibodies may make the drug even less effective. patients have high hopes for rapid skin clearance, so with every failed drug, there is less confidence and hope in the science of medicine and in the dermatologist.37 adherence may be negatively impacted with each new drug that has to be prescribed. the mind.px precision medicine test could improve clinical practice in these important ways as well as reducing costs to the medical system. payer impact the value to a payer of a diagnostic tool to determine a priori patient response to a drug is ultimately dependent on several factors. immediate and future drug spend savings are variable and may be significant based on the difference in post-rebate price the payer ultimately pays for the original drug and the drug being switched to. using a precision medicine test to determine a priori response forces a shift in drug utilization that deviates from formulary tiering, which does not take patient response into account, creating leverage to negotiate better rebates depending on the change in use as some increase would be expected for some mechanisms of action (moas) and attributable to the lowest cost drug. in order to proactively negotiate for the best price per drug class, each payer can model the effects of using the precision medicine test on their respective share of each drug/class and consider their pharmacy benefit manager’s (pbm’s) ability to adjust the formulary accordingly. however, pbm-rebate administration is a significant source of revenue, which could be impacted by use of a precision medicine testing strategy that decreases use of certain classes of drugs if countermeasures in the form of other economic incentives are not put in place for the pbm. limitations this study did not consider indirect patient skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 382 costs or the cost of the mind.px precision medicine test, thus net savings could not be concluded. because there are no currently published data with the use of mind.px in clinical practice, no direct health outcomes or cost benefits could be determined. additionally, the current model does not contemplate any potential differential response between those patients who have prior biologic exposure and those that are biologic naïve. these limitations should be considered for future analyses of the mind.px precision medicine test and its overall pharmacoeconomic impacts. the clinical utility of precision medicine testing has previously been demonstrated in other indications as an effective means to lower the economic burden of high-cost drugs and improve overall health outcomes of patients. this study applied similar principles for biologic psoriasis treatment and found that the utilization of precision medicine testing resulted in significant drug cost and wasted spending savings, a financial benefit which will impact payers, clinicians, and patients in substantial ways. because clinicians currently do not have a means to evaluate a patient’s genomic/transcriptomic profile for a biomarker response prior to prescribing a biologic for psoriasis treatment, the clinician must use a trial-and-error approach. this often leads to patients being initiated on nonoptimal treatment and requiring trials with multiple medications, resulting in an overall higher treatment cost. the findings from this study show that in a hypothetical world with a precision medicine test as described, payers will save on the cost of biologic psoriasis treatment by using such testing to ensure that the most effective biologic is utilized first. conflict of interest disclosures: p. montgomery, t. dickerson, and m. gross are employees of mindera. m. fried, l. chaihorsky, h. mamuszka, and b. long are employees of alva10, which received funding from mindera to conduct analysis. m. l. snyder has no relevant disclosures. dr. wu is or has been an investigator, consultant, or speaker for abbvie, almirall, amgen, arcutis, aristea therapeutics, boehringer ingelheim, bristol-myers squibb, dermavant, dr. reddy's laboratories, eli lilly, galderma, janssen, leo pharma, mindera, novartis, regeneron, sanofi genzyme, solius, sun pharmaceutical, ucb, valeant pharmaceuticals north america llc, and zerigo health. funding: this study was funded by mindera corporation. corresponding author: jashin j. wu, md, faad dermatology research and education foundation irvine, ca 92620 phone: (858) 768-9646 email: jashinwu@gmail.com references: 1. mehrmal s, uppal p, nedley n, giesey rl, delost gr. the global, regional, and national burden of psoriasis in 195 countries and territories, 1990 to 2017: a systematic analysis from the global burden of disease study 2017. j am acad dermatol. 2021;84(1):46-52. 2. michalek im, loring b, john sm. a systematic review of worldwide epidemiology of psoriasis. j eur acad dermatol venereol. 2017;31(2):205212. doi:10.1111/jdv.13854 3. brezinski ea, dhillon js, armstrong aw. economic burden of psoriasis in the united states: a systematic review. jama dermatol. 2015;151(6):651-658. doi:10.1001/jamadermatol.2014.3593 4. wu jj, feldman s, rastogi s. comparison of the cost-effectiveness of biologic drugs used for moderate-to-severe psoriasis treatment in the united states. journal of dermatological treatment. 2018. 5. liu j, thatiparthi a, martin a, egeberg a, wu jj, prevalence of psoriasis among adults in the u.s. 2009-2010 and 2013-2014 national health and nutrition examination surveys. journal of the american academy of dermatology (2020), doi: https://doi.org/10.1016/j.jaad.2020.10.035. conclusion skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 383 6. evans c. managed care aspects of psoriasis and psoriatic arthritis. american journal of managed care. 2016. 22:s238-s243 7. pilon d, teeple a, zhdanava m, et al. the economic burden of psoriasis with high comorbidity among privately insured patients in the united states. j med econ. 2019;22(2):196203. doi:10.1080/13696998.2018.1557201 8. arthur m. institute for health metrics and evaluation. nursing standard. 2014. 9. verbelen m, weale me, lewis cm. costeffectiveness of pharmacogenetic-guided treatment: are we there yet?. pharmacogenomics j. 2017;17(5):395-402. doi:10.1038/tpj.2017.21 10. faruque f, noh h, hussain a, neuberger e, onukwugha e. economic value of pharmacogenetic testing for cancer drugs with clinically relevant drug-gene associations: a systematic literature review. j manag care spec pharm. 2019;25(2):260-271. doi:10.18553/jmcp.2019.25.2.260 11. u.s. bureau of labor statistics, consumer price index for all urban consumers: medical care in u.s. city average [cpimedsl], retrieved from fred, federal reserve bank of st. louis; https://fred.stlouisfed.org/series/cpimedsl, december 30, 2020. 12. decision resource group (drg), market forecast dashboard psoriasis 2018 – 2028. april 2020. 13. cimzia [package insert]. smyrna, ga: ucb, inc; 2016. 14. ucb-usa.com. https://www.ucbusa.com/responsibility/affordability/cimziapricing-info. published 2021. accessed september 1, 2020. 15. enbrel [package insert]. thousand oaks, ca: immunex corporation; 2012. 16. enbrel.com. https://www.enbrel.com/support/financial-support. published 2020. accessed september 1, 2020. 17. erelzi [package insert]. princeton, nj: sandoz inc.; 2016. 18. https://www.goodrx.com/. published 2020. accessed september 1, 2020. 19. humira [package insert]. north chicago, il: abbvie inc.; 2018. 20. https://www.goodrx.com/. published 2020. accessed september 9, 2020. 21. inflectra [package insert]. lake forest, il: hospira; 2016. 22. remicade [package insert]. horsham, pa: janssen biotech inc.; 2013. 23. renflexis [package insert]. kenilworth, nj: merch sharp & dohme corp.; 2017. 24. cosentyx [package insert]. east hanover, nj: novartis pharmaceuticals corp.; 2016. 25. siliq [package insert]. bridgewater, nj: valeant pharmaceuticals north america llc; 2017. 26. taltz [package insert]. indianapolis, in: eli lilly and company; 2017. 27. lillypricinginfo.com. https://www.lillypricinginfo.com/taltz. published 2020. accessed september 1, 2020. 28. ilumya [package insert]. whitehouse station, nj: merck & co., inc.; 2018. 29. ilumya prices, coupons & patient assistance programs drugs.com. drugs.com. https://www.drugs.com/price-guide/ilumya. published 2020. accessed september 1, 2020. 30. skyrizi [package insert]. north chicago, il: abbvie inc.; 2019. 31. stelara [package insert]. horsham, pa: janssen biotech, inc.; 2016. 32. tremfya [package insert]. horsham, pa: horsham, pa; 2017. 33. menter a, strober b, personal communication, october 16, 2020. 34. chaihorsky l, fried m, long b, mamuszka h, harrington t, lukazewski a,. modeling the impact and value of a precision medicine approach from a payer perspective: an economic evaluation of stratifying rheumatoid arthritis patients for response to anti-tnf inhibitors prior to treatment. jmcp. 2021 35. wu jj, pelletier c, ung b, tian m, khilfeh i, curtis jr. real-world switch patterns and healthcare costs in biologic-naive psoriasis patients initiating apremilast or biologics. j comp eff res. 2020;9(11):767-779. doi:10.2217/cer2020-0045 36. no dj, inkeles ms, amin m, wu jj. drug survival of biologic treatments in psoriasis: a systematic review. j dermatologtreat. 2018;29(5):460-466. doi:10.1080/09546634.2017.1398393 37. wu jj, armstrong aw, gordon kb, menter ma. practical strategies for optimizing management of psoriasis. semin cutan med surg. 2018;37(2s):s52-s55. doi:10.12788/j.sder.2018.012 38. menter a, gottlieb a, feldman sr, et al. guidelines of care for the management of psoriasis and psoriatic arthritis: section 1. overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics. j am acad dermatol. 2008;58(5):826850. doi: 10.1016/j.jaad.2008.02.039 39. enos, c. w., o’connell, k. a., harrison, r. w., mclean, r. r., dube, b., & van voorhees, a. s. (2021). psoriasis severity, comorbidities and treatment response differ among geographic skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 384 regions in the united states. jid innovations, 100025. https://doi.org/10.1016/j.xjidi.2021.100025 supplemental tables and figures table s1. baseline input variables drug cost discounts tnfα inhibitor 28% il-17 inhibitor 39% il-23 inhibitor 49% reduced efficacy tnfα inhibitor 50% il-17 inhibitor 25% il-23 inhibitor 25% mind.px test accuracy 91% future drug class mix tnfα inhibitor 50% il-17 inhibitor 25% il-23 inhibitor 25% skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 385 table s2. baseline aggregated characteristics of drug classes for tier 1 drug cycling. 13-week loading costs shows total costs of drug loading period plus maintenance costs for any remaining weeks up to the 13-week mark. 13-week maintenance costs shows the total maintenance cost for a 13-week period. response rate – average of drug pasi 75 and pga or iga efficacy. secondary response rate – average drug class response rate when a second drug is used in the same drug class after the first drug failed. drug class 13-week loading costs 13-week maintenance costs response rate secondary response rate patient mix percent tnfa inhibitor $15,811 $12,846 65% 33% 32% il-17 inhibitor $23,385 $10,857 66% 16% 27% il-23 inhibitor $27,667 $10,431 80% 20% 42% figure s1. sample payer formularies at 91% accuracy. the following parameters were used; future state class mix: tnfα inhibitor 50%, il-17 inhibitor 25%, il-23 inhibitor 25%; discount rate: tnfα inhibitor: 28%, il-17 inhibitor: 39%, il-23 inhibitor: 49%; reduced drug class efficacy: tnfα inhibitor: 50%, il-17 inhibitor: 25%, il-23 inhibitor: 25%. drug class mix percentages tnfα/il-17/il-23. skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 386 figure s2. scenario analyses a-f figure s3. one-way sensitivity analysis of scenarios a-f cost savings skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 387 figure s4. one-way sensitivity analysis of scenarios a-f wasted-spend savings skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 461 short communications – in reply reply: “terra firma-forme dermatosis, keratotic form” daniel j. callaghan iii, md1, kenneth a. arndt, md1 1skincare physicians, chestnut hill, ma abdalla and colleagues presented an interesting case of a hyperkeratotic variant of terra firma-forme dermatosis (duncan’s dirty dermatosis) which was not responsive to alcohol pads.1 the authors are correct in stating that isopropyl alcohol has traditionally been described as being both diagnostic and therapeutic for terra firmaforme dermatosis. this has even been termed the smart (skin modified by alcohol rubbing test) evaluation,2 and an extensive review of the literature including over 50 cases reinforce the value of alcohol for this condition.3-6 we present an additional case and offer an alternative treatment that may be of value in the rare instances where alcohol is not sufficient. the patient was a 27 year-old female who presented with a 1 month history of hyperpigmented macules and thin papules on her bilateral cheeks (figure 1). although a diagnosis of terra firma-forme dermatosis was favored, it was not a clear-cut diagnosis. a 70% isopropyl alcohol pad was rubbed vigorously on her cheek until she endorsed discomfort, which caused us to stop with no resolution of the lesions. at this point we questioned our leading diagnosis as it had failed the alcohol rubbing test. in past cases we had successfully removed tightly adherent material from the skin in similar cases resistant to alcohol with acetone, a potent solvent, and when acetone was rubbed on the skin the debris was removed with ease, confirming the diagnosis. solvents are compounds that are used to dissolve, suspend or extract other materials. the term ‘solvent’ comes from the latin root solv, which means “loosen”. isopropyl alcohol is a non-polar solvent which means it can dissolve other non-polar, organic substances. however, acetone is more nonpolar than isopropanol, is a more potent solvent and therefore may do a better job at dissolving the keratin and sebum found in these lesions. given the hyperkeratotic nature of the lesions in the reported patient, it is entirely possible a more potent solvent may have been effective in removing the hyperkeratosis thus avoiding manual debridement. to the editors figure 1. skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 462 conflict of interest disclosures: none funding: none corresponding author: daniel j. callaghan iii, md skincare physicians 1244 boylston street, suite 103 chestnut hill, ma 02467 tel: (641) 583-5212 email: danieljcallaghan3@gmail.com references: 1. abdalla j, cruse a, patel n, brodell r. "terra firma-forme dermatosis, keratotic form." skin the journal of cutaneous medicine [online], 3.3 (2019): 212-214. web. 22 may. 2019 2. greywal t, cohen pr. non-invasive methods to establish the diagnosis of terra firma-forme dermatosis: the smart (skin modified by alcohol rubbing test) evaluation and dermoscopy. dermatol online j. 2016 jun 15;22(6). pii: 13030/qt7jk6k6d9. 3. greywal t, cohen pr. terra firma-forme dermatosis: a report of ten individuals with duncan's dirty dermatosis and literature review. dermatol pract concept. 2015 jul 31;5(3):29-33. doi: 10.5826/dpc.0503a08. ecollection 2015 jul. 4. berk dr. terra firma-forme dermatosis: a retrospective review of 31 patients. pediatr dermatol. 2012 may-jun;29(3):297-300. doi: 10.1111/j.1525-1470.2011.01422.x. epub 2011 oct 4. 5. abdel-razek mm, fathy h. terra firma-forme dermatosis: terra firme-forme dermatosis diagnostic sign and treatment: a case report.. dermatol online j. 2015 oct 16;21(10). pii: 13030/qt4rq5x48c. 6. browning j, rosen t. terra firma-forme dermatosis revisited. dermatol online j. 2005 aug 1;11(2):15. mailto:danieljcallaghan3@gmail.com introduction • rosacea is a chronic skin condition characterized by erythema, inflammatory papules/pustules, or telangiectasia. it is estimated to affect ~16 million people in the us1,2 • fda-approved treatment for rosacea includes topical agents, such as metronidazole, azelaic acid, sulfacetamide 10%/sulfur 5%, and, recently, ivermectin, as well as oral doxycycline1,3 • oral tetracyclines, particularly minocycline and doxycycline, may be prescribed for moderate-to-severe rosacea; however, their use is associated with systemic aes1,3 • a novel, foam formulation of minocycline – fmx-103 – has been developed to facilitate local application and bioavailability of minocycline while preserving its efficacy for the treatment of rosacea • this was a randomized, multicenter, double-blind study evaluating the safety and efficacy of 2 different doses of the topical minocycline foam, fmx-103 1.5% and 3%, in the treatment of papulopustular rosacea, as compared with vehicle methods • phase 2, randomized, multicenter (18 sites in germany), double-blind, vehiclecontrolled clinical trial • evaluated the safety and efficacy of 2 doses of a topical once-daily minocycline foam (fmx-103 1.5% and 3%) compared with vehicle foam in the treatment of moderate-to-severe papulopustular rosacea (figure 1) – subjects were randomized 1:1:1 to receive treatment once daily (in the evening) for 12 weeks – safety and efficacy evaluations were performed at week 2, 4, 8, and 12, with an additional safety follow-up visit at week 16 figure 1. study design efficacy and safety end points • absolute ∆ inflammatory lesion count (primary end point) • iga: ≥2-grade improvement; “clear” or “almost clear” • safety and tolerability n=232a week 12baseline fmx 103 3% (once daily) (n=75) foam vehicle (once daily) (n=78) fmx 103 1.5% (once daily) (n=79) week 16week 4 week 8week 2 follow-up period inclusion criteria • healthy males/nonpregnant females, aged ≥18 years • moderate-to-severe rosacea for ≥6 months, with ≥12 inflammatory facial lesions (papules/pustules) r an d o m iz e d 1 :1 :1 aa total of 233 subjects were randomized; however, 1 subject in the fmx-103 3% group did not receive treatment and was not included in the intent-to-treat analysis. results • 232 subjects were randomized and received at least one dose of study drug (itt population) – 201 (86.6%) subjects completed 12 weeks of treatment and the follow-up visit • baseline demographics and disease characteristics are shown in table 1 – ~50% to 60% of subjects had severe rosacea; the mean number of inflammatory lesions ranged from 30.6 to 34.5 table 1. baseline demographics and disease characteristics fmx-103 1.5% (n=79) fmx-103 3% (n=75) vehicle (n=78) overall (n=232) mean age, years (range) 51.2 (21-82) 51.6 (22-78) 54.8 (24-80) 52.5 (21-82) gender, % male / female 32.9 / 67.1 32.0 / 68.0 47.4 / 52.6 37.5 / 62.5 race, % caucasian 98.7 97.3 100.0 98.7 othera 1.3 2.7 0 1.3 iga of rosacea, %b moderate (iga=3) 43.0 38.7 51.3 44.4 severe (iga=4) 57.0 61.3 48.7 55.6 mean (±sd) total inflammatory lesion count 34.5 (±20.89) 34.1 (±24.99) 30.6 (±15.48) 33.1 (±20.74) an=1 other (fmx-103 1.5%); n=1 american indian or alaska native, n=1 native hawaiian or other pacific islander (fmx-103 3%). biga grading for rosacea: 0=clear; 1=almost clear; 2=mild; 3=moderate; 4=severe. • at week 12, both fmx-103 1.5% and 3% doses significantly reduced the number of papules and pustules vs vehicle (p<.001) (figure 2a) – significant reduction in lesion count was observed as early as week 2 • the corresponding percentage reductions in inflammatory lesions were 61.4% and 55.5% for fmx-103 1.5% and 3%, respectively, vs 29.7% for vehicle at week 12 (p<.001) (figure 2b) figure 2. change in inflammatory lesion counts from baseline by visit fmx-103 1.5% (n=79) fmx-103 3% (n=75) vehicle (n=78) fmx-103 1.5% (n=79) fmx-103 3% (n=75) vehicle (n=78) • significantly more fmx-103 1.5% and 3% subjects achieved ≥2-grade improvement in iga (figure 3a) and iga score of “clear” or “almost clear” vs vehicle at week 12 (figure 3b) – significantly more fmx-103 subjects had improvement of ≥2 iga grades as early as week 4 • there was no statistically significant difference between the fmx-103 1.5% and 3% groups figure 3. improvement in iga score from baseline by visit fmx-103 1.5% (n=79) fmx-103 3% (n=75) vehicle (n=78) fmx-103 1.5% (n=79) fmx-103 3% (n=75) vehicle (n=78) safety • both fmx-103 1.5% and 3% doses appeared to be generally safe and well tolerated, with no reported treatment-related systemic aes – overall, 47% (109/232) of subjects reported ≥1 teae (table 2) – the most common aes (≥2% of subjects) included nasopharyngitis, urinary tract infection, cystitis, and bronchitis (table 3) – 11 (4.7%) subjects reported treatment-related teaes; 9 had treatmentrelated dermal reactions (tables 2, 4) – serious teaes were reported in 4 subjects (3 in fmx-103 groups and 1 in vehicle group) (tables 2, 4) – 4 subjects discontinued the study due to teaes; only 3 subjects discontinued due to dermal-related teaes (skin and subcutaneous tissue disorders) (tables 2, 4) table 2. summary of safety profile overall summary of teaes, n (%) fmx-103 1.5% (n=79) fmx-103 3% (n=75) vehicle (n=78) subjects with ≥1 teae 46 (58.2) 32 (42.7) 31 (39.7) subjects with ≥1 treatment-related teaea 2 (2.5) 4 (5.3) 5 (6.4) treatment-related dermal reactionsb,c 1 (1.3) 3 (4.0) 5 (6.4) subjects with ≥1 serious teae 2 (2.5) 1 (1.3) 1 (1.3) subjects with ≥1 teae leading to study discontinuation 0 3 (4.0) 1 (1.3) safety population includes all randomized subjects who applied at least one dose of study drug. aincludes unassessable, possible, probable, and certainly related aes. bincludes skin and subcutaneous tissue disorders, and general disorders and administration-site conditions (ie, application-site erythema). csubjects experiencing ≥1 ae are counted only once for each ae term. table 3. summary of teaes in ≥2% of subjects common teaes (≥2% of subjects), n (%)a fmx-103 1.5% (n=79) fmx-103 3% (n=75) vehicle (n=78) nasopharyngitis 11 (13.9) 3 (4.0) 9 (11.5) urinary tract infection 3 (3.8) 2 (2.7) 3 (3.8) cystitis 2 (2.5) 2 (2.7) 0 bronchitis 3 (3.8) 0 0 urinary tract infection bacterial 2 (2.5) 0 0 influenza 0 0 2 (2.6) rosacea 2 (2.5) 3 (4.0) 0 eczema 2 (2.5) 2 (2.7) 2 (2.6) hypertension 2 (2.5) 2 (2.7) 2 (2.6) eczema eyelids 2 (2.5) 0 0 toothache 2 (2.5) 0 0 headache 0 2 (2.7) 0 safety population includes all randomized subjects who applied at least one dose of study drug. asubjects experiencing ≥1 ae are counted only once for each ae term. table 4. summary of treatment-related dermal reactions, serious teaes, and teaes leading to study discontinuation fmx-103 1.5% (n=79) fmx-103 3% (n=75) vehicle (n=78) subjects with treatment-related dermal reactions, n (%)a,b 1 (1.3) 3 (4.0) 5 (6.4) rosacea 0 2 (2.7) 0 eczema 0 1 (1.3) 1 (1.3) skin exfoliation 0 1 (1.3) 0 erythema 0 0 1 (1.3) pruritus 0 0 1 (1.3) scab 0 0 1 (1.3) skin burning sensation 0 0 1 (1.3) application-site erythema 1 (1.3) 0 1 (1.3) subjects with ≥1 serious teae, n (%)b 2 (2.5) 1 (1.3) 1 (1.3) hemorrhoids 0 1 (1.3) 0 contusion 1 (1.3) 0 0 cerebral hemorrhage 1 (1.3) 0 0 hemiparesis 1 (1.3) 0 0 pulmonary embolism 1 (1.3) 0 0 gastroenteritis 0 0 1 (1.3) subjects with ≥1 teae leading to study discontinuation, n (%)b,c 0 3 (4.0) 1 (1.3) eczema 0 1 (1.3) 0 rosacea 0 1 (1.3) 0 pruritus 0 0 1 (1.3) skin burning sensation 0 0 1 (1.3) burning sensation 0 1 (1.3) 0 safety population includes all randomized subjects who applied at least one dose of study drug. aincludes skin and subcutaneous tissue disorders, and general disorders and administration-site conditions (application-site erythema). bsubjects experiencing ≥1 ae are counted only once for each ae term. ceczema, rosacea, pruritus, and skin burning sensation were classed as skin and subcutaneous tissue disorders (dermal related); burning sensation was classified as a nervous system disorder. conclusions • at week 12, both fmx-103 1.5% and fmx-103 3% were significantly better than vehicle in – reducing the number of papules and pustules – improving iga score by ≥2 grades – achieving iga of “clear” or “almost clear” (score 0 or 1) • both fmx-103 doses appeared to be generally safe and well tolerated, with no reported treatment-related systemic aes – only 3 subjects discontinued the study due to dermal-related teaes • these results indicated that fmx-103 appeared to be an effective, safe, and well tolerated treatment for moderate-to-severe papulopustular rosacea • the results support further investigation in a larger, phase 3 clinical trial references 1. oge lk, et al. am fam physician. 2015;92:187-196. 2. national rosacea society. rosacea review. www.rosacea.org/rr/2010/winter/article_1.php. accessed december 5, 2016. 3. american acne & rosacea society. rosacea medical management guidelines. www.acneandrosacea.org/sites/default/files/aars_rosacea_guidelines_2007.pdf. accessed december 5, 2016. abbreviations: ae=adverse event; teae=treatment emergent adverse event; iga=investigator’s global assessment; itt=intent-to-treat; sd=standard deviation. disclosure: foamix pharmaceuticals, inc., sponsored this study. acknowledgment: editorial support was provided by giang nguyen, phd, of p-value communications. topical minocycline foam (fmx-103) for the treatment of moderate-to-severe rosacea: results of a phase 2, randomized, double-blind, multicenter clinical study ulrich mrowietz1, tal hetzroni kedem2, rita keynan2, meir eini2, dov tamarkin2, mitchell shirvan2 1university medical center schleswig-holstein, campus kiel, germany; 2foamix pharmaceuticals, ltd., rehovot, israel. fc17posterfoamixmrowietztopicalminocyclinerosacea.pdf skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 341 brief articles dermoscopy of inflammatory linear verrucous epidermal nevus: brown and red glomerular structures over a white background as an identifying feature jeffrey dickman, ba1, michael noparstak, do2, rajiv nathoo, md2 1honorhealth internal medicine residency 2orlando dermatology residency inflammatory linear verrucous epidermal nevus (ilven) is an uncommon variant of keratinocytic epidermal nevus that typically presents as linear erythematous and verrucous papules which often coalesce into plaques. ilven is characteristically intensely pruritic and is most commonly found unilaterally on an extremity, the trunk, or buttock in a blaschkoid pattern. lesions may be present as early as birth most commonly developing in early childhood before the age of five years old and persisting for months to years. females are more often affected.1,2 we present the case of an adult patient who presented to our clinic for evaluation of her long-standing, treatment-resistant ilven. dermoscopy was used to aid in the diagnosis and exhibited alternating red and brown glomerular-type structures over a white background. we propose that these findings may be added to other previously documented dermoscopic characteristics of ilven, as they correspond to known histopathological features of the dermatosis and may aid in non-invasive diagnosis. a 28-year-old hispanic female presented to our clinic complaining of pruritic linear bumps on her left arm, shoulder, and leg. she had previously seen a dermatologist for the same lesions and reported that a biopsy was performed at that time which showed psoriasiform dermatitis consistent with inflammatory linear verrucous epidermal nevus. she was treated with topical tretinoin but had no improvement. the patient had no other significant past medical, surgical, or family history. she was not taking any medications and had no allergies. on physical exam brown-to-violaceous-tored plaques were present in a unilateral blaschkoid distribution along the left arm, left shoulder, and left leg, consistent with the diagnosis of inflammatory linear verrucous epidermal nevus. (figs. 1-2) dermoscopic exam revealed alternating brown and red glomerular-type structures, visualized over a white background. (fig. 3) no biopsy was performed. the patient was started on a combination of topical steroid, topical calcipotriene, and topical retinoid. introduction case report skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 342 figure 1. verrucous plaques distributed in a blaschkoid pattern on the left upper extremity. figure 2. inflammatory plaques in a blaschkoid distribution on the left thigh. diagnosis of ilven requires careful consideration of other linear and blaschkoid dermatoses. linear psoriasis resembles ilven both clinically and histologically. linear lichen planus, lichen striatus, and other epidermal nevi, among others, make up the differential diagnosis.3 histological examination of ilven reveals psoriasiform hyperplasia of the epidermis and broad zones of parakeratosis without a granular layer that alternate with zones of orthokeratosis and hypergranulosis. other findings may include mild epidermal spongiosis, a superficial infiltrate of lymphocytes and neutrophils, and dilated vessels in the dermal papillae.3,4 figure 3. dermoscopic view showing alternating brown and red glomerular-type structures over a white background. dermoscopy has also become a useful tool in the diagnosis of ilven. carbotti et al described the dermoscopic features of verrucous epidermal nevi (ven), including large brown circles present in all observed lesions. these large brown circles may correspond to pigmented keratinocytes surrounding the elongated dermal papillae but are not specific to ven.5 kim et al described dermoscopic features of ilven, reporting prominent findings of scales, brown color, a cerebriform patterned structure, and dotted vascular patterns. a glomerular vascular pattern was seen in one patient.6 dermoscopy at two affected sites in our patient revealed alternating brown and red glomerular-type structures. the correlation of these structures to the known histopathological features of ilven increases the yield of the non-invasive discussion skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 343 clinical diagnosis. pigmented keratinocytes in alternating zones of orthokeratosis and parakeratosis may be the source of the glomerular brown structures seen on dermoscopy. dilated vessels in the dermal papillae correspond to the red glomerular structures that were also seen. these structures were visualized over a white background, which is consistent with the findings of one patient described by kim et al.6 ilven is an uncommon dermatosis and the description of its dermoscopic features has thus far been very limited. our case is unique because of the presence of alternating brown and red glomerular-type structures on a white background. while these findings are unique, the visualized structures correspond to known histopathologic features of ilven and are therefore helpful in making a non-invasive diagnosis. further studies and case reports will be valuable in establishing the characteristic dermoscopic features of ilven. conflict of interest disclosures: none funding: none corresponding author: jeffrey dickman, ba 151 southhall lane #300, maitland, fl 32751 321-594-5530 jdickman26@midwestern.edu references: 1. lee sh, rogers m. inflammatory linear verrucous epidermal naevi: a review of 23 cases. australas j dermatol. 2001 nov;42(4):252-6. pubmed pmid: 11903156. 2. asch s, sugarman jl. epidermal nevus syndromes: new insights into whorls and swirls. pediatr dermatol. 2018 jan;35(1):21-29. doi: 10.1111/pde.13273. epub 2017 oct 16. review. pubmed pmid: 29044700. 3. khachemoune a, janjua sa, guldbakke kk. inflammatory linear verrucous epidermal nevus: a case report and short review of the literature. cutis. 2006 oct;78(4):261-7. review. pubmed pmid: 17121063. 4. kosann mk. inflammatory linear verrucous epidermal nevus. dermatol online j. 2003 oct;9(4):15. pubmed pmid: 14594588. 5. carbotti m, coppola r, graziano a, verona rinati m, paolilli fl, zanframundo s, panasiti v. dermoscopy of verrucous epidermal nevus: large brown circles as a novel feature for diagnosis. int j dermatol. 2016 jun;55(6):653-6. doi: 10.1111/ijd.12948. epub 2015 oct 16. pubmed pmid: 26475079. 6. kim dw, kwak hb, yun sk, kim hu, park j. dermoscopy of linear dermatosis along blaschko's line in childhood: lichen striatus versus inflammatory linear verrucous epidermal nevus. j dermatol. 2017 dec;44(12):e355-e356. doi: 10.1111/1346-8138.14035. epub 2017 sep 18. pubmed pmid: 28925078. conclusion mailto:jdickman26@midwestern.edu skin january 2018 volume 2 issue 1 copyright 2018 the national society for cutaneous medicine 54 brief articles disordered presentation of paraneoplastic pancreatitis, polyarthritis, and panniculitis syndrome in a patient with end-stage pancreatic cancer melody maarouf mhs a , marilyn r. wickenheiser md b , james e. sligh jr. md phd b,c , keliegh culpepper md d , vivian y. shi md b a university of arizona, college of medicine, az b university of arizona, department of medicine, division of dermatology, az c southern arizona va healthcare system, az d dermpath diagnostics, tucson, az a 53-year-old male presented with a onemonth history of worsening polyarthralgia involving all joints of the upper and lower extremities. he was diagnosed with stage iv unresectable beta-islet neuroendocrine pancreatic cancer with liver metastasis 5 months prior, and had been receiving chemotherapy (capecitabine/temozolamide) for 1 month. clinical examination revealed diffusely tender joints involving hands, feet, knees, and elbows. vital signs, cardiopulmonary and abdominal exams were unremarkable. initial laboratory investigation revealed leukocytosis (wbc 34.4 1000/ul, neutrophils 91%), elevated lipase (25,560 u/l) and inflammatory indices (crp: 27.05 mg/dl; esr 48 mm/hr; ldh 503 iu/l). autoimmunity (ana/rheumatoid factor) and infectious disease workup (hiv, hcv, hbv, gonorrhea/chlamydia, cryptococcus, brucella, lyme, and coccidioidomycosis) were negative. serum rickettsial igg was weakly positive, and igm was negative. serum uric acid, urine uric acid, and triglycerides were normal. mri revealed cellulitis with a soft tissue ulcer on the left ankle and abscesses suspicious for septic tenosynovitis on the right wrist. bacterial and fungal cultures of knee, ankle, and elbow joint aspirations were negative except for the single most painful joint, which expressed a purulent aspirate growing few gram-positive cocci. initial treatment for suspected septic arthritis with broad-spectrum antibiotics, prednisone, nsaids, and opiates inadequately controlled his symptoms. excruciating pain prevented activities of daily living, prompting hospital admission. abstract pancreatitis, polyarthritis, and panniculitis (ppp) syndrome is a rare triad with variable initial presentations. we report a case of ppp due to stage iv pancreatic cancer presenting with polyarthritis following chemotherapy induction, whose diagnosis was delayed due to late manifestation of pancreatic panniculitis. case report skin january 2018 volume 2 issue 1 copyright 2018 the national society for cutaneous medicine 55 approximately one month after onset of polyarthralgia, tender erythematous plaques (figure 1) developed on the posterior legs. histopathologic examination of punch biopsy confirmed lobular panniculitis with necrosis of adipocytes and a mixed inflammatory infiltrate (figure 2). figure 1. clinical manifestation of pancreatic panniculitis: the clinical presentation of pancreatic panniculitis is characterized by erythematous, ill-defined, reddish-brown macules or nodules that may be painful or painless. figure 2. histopathologic images of pancreatic panniculitis. a. the pattern of adipocyte necrosis, known as “ghost cells,” is characteristic of pancreatic panniculitis. b. perifollicular adipose tissue is also involved. a b skin january 2018 volume 2 issue 1 copyright 2018 the national society for cutaneous medicine 56 the triad of pancreatic disease, panniculitis, and polyarthritis is referred to as ppp syndrome, which occurs in 0.3-1% of patients with benign or malignant pancreatic disease. 1 acute or chronic pancreatitis is the most commonly implicated pancreatic disorder, however, of the malignancies, acinar cell carcinoma is the most common culprit. rarely, islet cell carcinomas are associated, and represent only 1-2% of ppp cases. relation to carcinoma renders ppp syndrome a paraneoplastic phenomenon, 2 and is a hallmark of poor prognosis, with a 4.75-months median survival after initial cutaneous eruption. 1 ppp syndrome is typically diagnosed clinically. 5 nevertheless, histopathologic findings of pancreatic panniculitis include adipocyte destruction and necrosis, which results in “ghost cells” that lack nuclei and may have basophilic granular cytoplasm from calcium deposition via saponification. panniculitis characteristically appears as tender, erythematous to red-brown nodules, frequently present on the lower extremities. in severe cases, nodules may ulcerate and drain an oily, brown, sterile substance. arthritis is reported in approximately 56% of patients with ppp syndrome, and most commonly affects small joints of the hands, wrists, and feet. joint aspirate typically yields a purulent appearing fluid that lacks white cells or microorganisms, but may include lipid liquid crystals. 5 in 45% of these patients, arthritis follows a chronic course with poor response to nsaids and immunosuppressants, and may persist even after normalization of serum pancreatic enzymes. 7 the pathogenesis of ppp has not entirely been elucidated. the leading hypothesis suggests that pancreatic parenchyma disruption causes release of pancreatic enzymes into the circulation, hydrolyzing fat lobules into glycerol and free fatty acids. these byproducts saponify adipose tissues, resulting in panniculitis, as well as polyarthritis via infiltration of the periarticular fat pads. 3,4 this hypothesis is supported by concomitant panniculitis and polyarthritis in approximately 50% of patients who have a fistula within the pancreatic portal system. 5 notably, serum pancreatic enzyme levels do not always correlate with disease presence or severity. in in-vitro studies, incubation of human subcutaneous fat with serum containing high levels of pancreatic lipase, trypsin, and amylase has not yielded panniculitic pathology. 6 management of ppp syndrome is frequently aimed at treating the underlying pancreatic disease. 8 panniculitis typically resolves following the resolution of the acute inflammation of the pancreatic parenchyma. thus, supportive treatment, such as fluids and pain control, is all that is required. panniculitis associated with pancreatic carcinoma tends to persist due to the difficulty in treating pancreatic carcinoma. 5 patients with pancreatic carcinoma may require alternative therapy for symptomatic management. in a case report, ocreotide has demonstrated potential in slowing progression and reversing manifestations of ppp associated with pancreatic carcinoma. however, the positive implications of this therapy have been difficult to replicate. 9 cutaneous manifestation is commonly the initial presenting symptom of ppp syndrome, and may precede detection of pancreatic pathology by months. 5 the literature consistently reports patients presenting with polyarthralgia and concomitant cutaneous findings, but mild or absent abdominal symptoms. thus discussion skin january 2018 volume 2 issue 1 copyright 2018 the national society for cutaneous medicine 57 pancreatic pathology is typically the last of the triad to be detected. 8 the delay in diagnosing the etiology of the debilitating arthralgias in our patient is due to ppp syndromes’ rarity and his disordered presentation. to our knowledge, our patient is the first case in which cutaneous manifestations appeared months later than the other components of the syndrome. our patient presented with abdominal pain, with a work up that revealed pancreatic carcinoma. joint pain occurred concurrently with the induction of chemotherapy. cutaneous eruption of panniculitis occurred two months following joint pain presentation. it is notable that the patient developed arthralgias and cutaneous manifestations following the initiation of chemotherapy. the overwhelming lysis of tumor cells from chemotherapy could have led to destruction of pancreatic parenchyma, and increased distribution of pancreatic enzymes. this case raises awareness for possible pancreatic disease or malignancy in the presence of polyarthralgia and panniculitis. our case highlights the potential for delayed cutaneous manifestation in ppp. prompt diagnosis can allow judicious treatment of pancreatic pathology and prompt implementation of appropriate therapy. conflict of interest disclosures: no relevant conflict of interest. funding: none. corresponding author: vivian y. shi, md assistant professor of medicine (dermatology division) arizona cancer center 1515 n. campbell ave. (po box 245024) building #222, levy bldg., 1906e tucson, az 85724-5024 520-626-6024 (office) 520-626-6033 (fax) vshi@email.arizona.edu references: 1. zhang g, cao z, yang g, wu w, zhang t, zhao y. pancreatic panniculitis associated with pancreatic carcinoma: a case report. medicine (baltimore). 2016;95(31):e4374. 2. borowicz j, morrison m, hogan d, miller r. subcutaneous fat necrosis/panniculitis and polyarthritis associated with acinar cell carcinoma of the pancreas: a rare presentation of pancreatitis, panniculitis and polyarthritis syndrome. j drugs dermatol. 2010;9(9):1145-1150. 3. zundler s, erber r, agaimy a, et al. pancreatic panniculitis in a patient with pancreatic-type acinar cell carcinoma of the liver--case report and review of literature. bmc cancer. 2016;16:130. 4. fraisse t, boutet o, tron am, prieur e. pancreatitis, panniculitis, polyarthritis syndrome: an unusual cause of destructive polyarthritis. joint bone spine. 2010;77(6):617-618. 5. garcia-romero d, vanaclocha f. pancreatic panniculitis. dermatol clin. 2008;26(4):465-470, vi. 6. requena l, sanchez yus e. panniculitis. part ii. mostly lobular panniculitis. j am acad dermatol. 2001;45(3):325-361; quiz 362-324. 7. narvaez j, bianchi mm, santo p, et al. pancreatitis, panniculitis, and polyarthritis. semin arthritis rheum. 2010;39(5):417-423. skin january 2018 volume 2 issue 1 copyright 2018 the national society for cutaneous medicine 58 8. ferri v, ielpo b, duran h, et al. pancreatic disease, panniculitis, polyarthrtitis syndrome successfully treated with total pancreatectomy: case report and literature review. int j surg case rep. 2016;28:223-226. 9. price-forbes an, filer a, udeshi ul, rai a. progression of imaging in pancreatitis panniculitis polyarthritis (ppp) syndrome. scand j rheumatol. 2006;35(1):72-74. skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 134 rising derm stars® development and validation of the tape-to-trace method: an objective outcome measure for linear postoperative scars stephanie feldstein, md1, reason wilken1, md, jenny wang, md,1 and daniel eisen, md1 1department of dermatology, uc davis, sacramento, ca background/objectives: several outcome measures exist for assessing postoperative linear scars, though all have shortcomings. subjective scales like the patient and observer scar assessment scale (posas) aggregate scores from various physical scar parameters into an overall score proportional to scar severity. despite being validated in multiple studies1, posas has been subject to interand intra-rater discrepancies due to factors such as observer expertise and scar type, and the surface area has been shown to have a low correlation with overall opinion2. as a result, several instruments have been developed to help clinicians measure scar surface area in an objective way. however, these devices are often cumbersome and expensive, and therefore rarely adopted in the clinical setting. planimetry is a valid and reliable method for assessing wound surface area, but only mathematically accurate for square or rectangular wounds3. computerassisted planimetry is more accurate but still requires meticulous tracing of the scar onto transparent film and analysis with proprietary computer software4. we have devised a simple and inexpensive method of assessing scar surface area called the trace-to-tape method. with this technique, an observer traces a scar with a water-based gel pen applied directly to the skin. the gel residue is then transferred onto clear tape to be scanned into the computer. using the free image-processing program imagej, the total scar surface area and mean scar width can be calculated. methods: twenty patients with postoperative scars greater than one month old were recruited from our dermatology clinic. scars were evaluated by two independent observers using our trace-to-tape method, posas, and manual planimetry. we then tested the feasibility and interand intra-rater reliability of our trace-to-tape method as well as its validity by comparing it to posas and manual planimetry. results: trace-to-tape and manual planimetry methods yielded similarly high intra-rater and inter-rater reliabilities, but the confidence limits for the trace-to-tape method were considerably smaller (table 1). mean scar width and posas surface area scores were significantly positively correlated (rho = 0.62 p = 0.003) as were mean scar width and posas overall opinion scores (rho = 0.69, p < 0.001) (figure 1). limitations: we were primarily limited by the number of observers and lack of blinding. discussion: having an objective outcome measure for postoperative scars is important for conducting clinical research and skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 135 establishing standards of care that maximize patient satisfaction. in our study, we found higher inter-rater reliability with the two objective assessment tools, manual planimetry and the tape-to-trace method, compared to posas. while surface area evaluated on posas has been shown to have low predictive value for the overall opinion of scars2, we found that our calculation of mean scar width accurately reflected the cosmetic appearance of scars. since scar width can vary along the length of the scar5, our technique of calculating mean scar width from the calculated surface area bypasses the measurement error from measuring scar width at a set point on the scar. though manual planimetry was found to be reliable and valid, accuracy depended on scar placement in relation to square grids, and inconsistencies arose when scar margins occupied partial boxes on the grid. the tape-to-trace method circumvented this limitation since it did not rely on a grid system. manual planimetry was also more cumbersome to perform on curved surfaces such as the face, since it was more difficult to flatten a transparent film over a curved surface. conclusion: the tape-to-trace method is a reliable objective scar assessment tool that correlates well with posas and is more accurate than manual planimetry. this novel method should be considered a practical and affordable option for objective scar assessment in the clinic and research setting. table 1: intraand inter-rater reliability estimates and 95% confidence limits derived from 5,000 bootstrap samples. intra-rater reliability estimates [95% confidence limits] trace-to-tape method 0.95 [0.85, 0.97] manual planimetry 0.94 [0.62, 0.97] inter-rater reliability trace-to-tape method (average) 0.97 [0.87, 0.99] manual planimetry method (average) 0.97 [0.66, 0.99] posas surface area 0.65 [0.46, 0.81] posas overall opinion 0.59 [0.12, 0.81] note: intra-rater reliability was not calculated for posas due to likelihood of recall bias. figure 1: relationship between scar width as determined with the trace-to-tape method and posas surface area score and posas overall opinion score. references: 1. van de kar al, corion lu, smeulders mj, draaijers lj, van der horst cm, van zuijlen pp. reliable and feasible evaluation of linear scars by the patient and observer scar assessment scale. plastic and reconstructive surgery. 2005;116(2):514-522. 2. liu x, nelemans pj, van winden m, kelleners-smeets nw, mosterd k. reliability of the patient and observer scar assessment scale and a 4-point scale in evaluating linear facial surgical 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 0. 2 0. 4 0. 6 0. 8 1. 0 posas surface area s ca r w id th 2 3 4 5 6 0. 2 0. 4 0. 6 0. 8 1. 0 overall posas score s ca r w id th skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 136 scars. j eur acad dermatol venereol. 2017;31(2):341-346. 3. van zuijlen pp, angeles ap, suijker mh, kreis rw, middelkoop e. reliability and accuracy of techniques for surface area measurements of wounds and scars. the international journal of lower extremity wounds. 2004;3(1):7-11. 4. sugama j, matsui y, sanada h, konya c, okuwa m, kitagawa a. a study of the efficiency and convenience of an advanced portable wound measurement system (visitrak). j clin nurs. 2007;16(7):1265-1269. 5. burgess lp, morin gv, rand m, vossoughi j, hollinger jo. wound healing. relationship of wound closing tension to scar width in rats. arch otolaryngol head neck surg. 1990;116(7):798-802. efinaconazole 10% and tavaborole 5% penetrate across poly-ureaurethane 16%: results of in vitro release testing and clinical implications of onychodystrophy in onychomycosis chris g. adigun md,a tracey c. vlahovic dpm,b michael b. mcclellan ms,c kailas d. thakker phd,c ryan r. klein phd,c tuan a. elstrom bs,d and daniel b. ward, jr., mddadermatology & laser center of chapel hill, chapel hill, nc • btemple university school of podiatry, philadelphia, pa • ctergus pharma, llc, durham, nc • , charleston, sc references supported by: abstr act introduction discussion study designmethods & results background: poly-ureaurethane has been previously described for the management of dry, brittle, and in general, dystrophic nails. the polymer yields a waterproof, breathable barrier to protect the nail plate and prevent further damage to the nail, while regulating transonychial water loss (towl). because nail dystrophy and dessication are contributing factors to onychomycosis, a barrier that protects the nail but also allows a topical antifungal to permeate its shield is potentially an advantageous combination. oral antifungals such as terbinafine, itraconazole, and fluconazole, as well as the newer topical antifungals efinaconazole and tavaborole (although formulated to penetrate the nail unit and work with the porosity and inherent electrical charge of the nail plate), do not take into account nail damage that has been created from years of harboring a dermatophyte infection. up to 50% of cases presumed to be onychomycosis are in fact onychodystrophy without fungal infection, and laboratory testing for fungus should be obtained prior to initiating antifungal treatment. whether a nail has onychomycosis, or onychodystrophy due to other causes, barrier function and structural integrity are compromised in diseased nails, and should be addressed. a poly-ureaurethane barrier that protects against wetting/ drying, fungal reservoirs, and microtrauma, followed by the addition of oral or topical antifungals after laboratory fungal confirmation may optomize outcomes in the treatment of onychomycosis. objective: the purpose of this work was to determine through in vitro release testing (ivrt) whether poly-ureaurethane 16% allows for penetration of efinaconazole 10% or tavaborole 5%. results could spur subsequent clinical studies which would have implications for the addition of an antifungal based on fungal confirmation, after addresssing the underlying nail dystrophy primarily. methods: a vertical diffusion cell system was used to evaluate the ability of efinaconazole 10% and tavaborole 5% to approximately half of all nail cases suspected to be onychomycosis, are in fact onychodystrophy due to other causes.1-4 a multitude of other disorders and diseases can lead to onychodystrophy, and for this reason, it is important to ensure an accurate diagnosis of the nail disease prior to beginning treatment. prescribing antifungal therapy for suspected, but not confirmed nail fungus is therefore not recommended, and fungal confirmation or exclusion is an important initial step to ensure that patients are correctly treated. however, whether a nail has onychomycosis, or onychodystrophy due to other causes, barrier function and structural integrity are compromised in diseased nails,5,6 and should be addressed. if fungus is indeed confirmed, oral and topical antifungal options are available. the newer topical products efinaconazole 10% and tavabarole 5%, were approved for the treatment of onychomycosis of toenails due to trichophyton rubrum or trichophton mentagrophytes.7,8 the efficacy in the phase iii trials was better than previously available topical antifungals, but remains below that of oral agents such as terbinafine and itraconazole,9-18 even with oral therapy in onychomycosis, recurrence rates the following equations were used to calculate flux and permeability: the flux and permeability of efinaconazole 10% and tavaborole 5% across poly-ureaurethane 16% were determined, and the data are summarized in table 1. based on the determined values, the experimental flux of both efinaconazole and tavaborole across poly-ureaurethane 16% was greater than previously reported values for the flux of these molecules across the nail alone.31,32 these results demonstrate that the flux of both efinaconazole and tavaborole across poly-ureaurethane would not be a limiting factor during concomitant use. results revealed greater variability in the tavaborole 5% data than in the efinaconazole 10% data, and may be due to physiochemical differences between the molecules. the mass of tavaborole (151.93 da) is less than half that of efinaconazole (348.39 da), and molecular size has an important effect on penetration. the smaller molecular size could influence variability in flux and permeability. in addition, the experimental time course for each compound was set based on previously noted differences in flux. the shorter sampling intervals for tavaborole as compared to efinaconazole could have contributed to the greater variability observed in tavaborole permeability. the key finding, however, is that poly-ureaurethane would not be limiting in the flux of these molecules during combination use. initial experiments to develop appropriate conditions guided the study design and suggested that the permeability of tavaborole across poly-ureaurethane 16% was much greater than efinaconazole; therefore, the sampling intervals were set accordingly for the two compounds. apparatus: vertical diffusion cells replicates: 12 vertical diffusion cells per formulation surface area: 1.0 cm2 poly-ureaurethane application method: applicator brush coats: one receptor volume: approximately 8 ml sampling intervals (tavaborole 5%): 5, 10, 15, 20, 25, 30, 40 and 60 minutes sampling intervals (efinaconazole 10%): 0.5, 1, 2, 4, 6, 20, 24, and 28 hours temperature: 32°c ± 0.5°c sample aliquot: 300 μl membrane: nylon, 0.45µm application method: positive displacement pipette application amount: 50 µl receiving medium (tavaborole): phosphate buffer, ph 7.0 receiving medium (efinaconazole): 10% hydroxypropyl-β-cyclodextrin sufficient poly-ureaurethane 16% was applied to the membrane extending outside the area defined by the donor chamber such that no exposed membrane remained when the vertical diffusion cell was fully assembled. polyureaurethane was applied and allowed to dry for 30 minutes prior to use. 1. allevato maj. diseases mimicking onychomycosis. clinics in dermatology. 2010; 28:164-177. 2. ghannoum ma, hajjeh ra, scher r, et al. a large-scale north american study of fungal isolates from nails: the frequency of onychomycosis, fungal distribution, and antifungal susceptibility patterns. j amacad dermatol. 2000; 43:641-648. 3. gupta ak, jain hc, lynde cw, et al. prevalence and epidemiology of onychomycosis in patients visiting physicians’ offices: a multicenter canadian survey of 15,000 patients. j am acad dermatol. 2000; 43:244-248. 4. american academy of dermatology. choosing wisely. http://www.choosingwisely.org/societies/american-academy-of-dermatology/. accessed july 27, 2016. 5. mcauley wj, jones sa, traynor mj, et al. an investigation of how fungal infection influences drug penetration through onychomycosis patient’s nail plates. eur j pharm biopharm. 2016; 102:178-84. doi: 10.1016/j. ejpb.2016.03.008 6. kitamori k, koyabashi m, akamatsu et al. weakness in intercellular association of keratinocytes in severely brittle nails. ach histol cytol. 2006; 69:323-328. 7. jublia [package insert]. bridgewater, nj: valeant pharmaceuticals north america llc; 2014. 8. kerydin [package insert]. palo alto, ca: anacor pharmaceuticals; 2014. 9. brautigam m, nolting s, schopf re, weidinger g. randomised double blind comparison of terbinafine and itraconazole for treatment of toenail tinea infection. seventh lamisil german onychomycosis study group. bmj. 1995; 311:919-22. erratum in: bmj 1995; 311:1350. 10. drake la, shear nh, arlette jp, et al. oral terbinafine in the treatment of toenail onychomycosis: north american multicenter trial. j am acad dermatol. 1997; 37:740-745. 11. scher rk, breneman d, rich p, et al. once-weekly fluconazole (150, 300, or 450 mg) in the treatment of distal subungual onychomycosis of the toenail. j am acad dermatol. 1998; 38:s77-86. 12. evans egv, sigurgeirsson b, for the lion study group. double blind, randomised study of continuous terbinafine compared with intermittent itraconazole in treatment of toenail onychomycosis. bmj. 1999; 318:1031-1035. 13. gupta ak, lynde cw, konnikov n. single-blind, randomized, prospective study of sequential itraconazole and terbinafine pulse compared with terbinafine pulse for the treatment of toenail onychomycosis. j am acad dermatol. 2001; 44:485-91. 14. warshaw em, fett dd, bloomfield he, grill jp, nelson db, quintero v, carver sm, zielke gr, lederle fa. pulse versus continuous terbinafine for onychomycosis: a randomized, double-blind, controlled trial. j am acad dermatol. 2005; 53:578-84. 15. penlac® (ciclopirox 8%) [package insert]. bridgewater, nj: dermik laboratories; 2006. 16. sporanox® (itraconazole) [package insert]. raritan, nj: pricara, division of ortho-mcneil-janssen pharmaceuticals, inc; 2011. 17. elewski be, rich p, pollak r, et al. efinaconazole 10% solution in the treatment of toenail onychomycosis: two phase iii multicenter, randomized, double-blind studies. j am acad dermatol. 2013; 68:600-608. 18. elewski be, aly r, baldwin sl, et al. efficacy and safety of tavaborole topical solution, 5%, a novel boronbased antifungal agent, for the treatment of toenail onychomycosis: results from 2 randomized phase iii studies. j am acad dermatol. 2015; 73:62-69. 19. tosti a, piraccini bm, stinchi c, colombo md. relapses of onychomycosis after successful treatment with systemic antifungals: a three-year follow-up. dermatol. 1998; 197:162-166. 20. sigurgeirsson b, olafsson jh, steinsson jb, et al: long-term effectiveness of treatment with terbinafine vs itraconazole in onychomycosis: a 5-year blinded prospective follow-up study. arch dermatol. 2002; 138:353. 21. scher rk, tavakkol a, sigurgeirsson b, et al. onychomycosis: diagnosis and definition of cure. j am acad dermatol. 2007; 56:939-944. 22. sigurgeirsson b, olafsson j, steinsson j, kerrouche n, sidou f. efficacy of amorolfine nail lacquer for the prophylaxis of onychomycosis over 3 years. j eur acad dermatol venereol. 2010; 24:910-915. 23. gupta ak, cooper ea, paquet m: recurrences of dermatophyte toenail onychomycosis during long-term follow-up after successful treatments with monoand combined therapy of terbinafine and itraconazole. j cutan med surg. 2013; 17:201. 24. scher rk, baran r. onychomycosis in clinical practice: factors contributing to recurrence. br. j dermatol. 2003; 149(s65):5-9. 25. vlahovic t. the use of poly-ureaurethane, 16% for dystrophic nails. podiatry management. 2013; 32:91-94. 26. daniel c, jellinek j. the pedal fungus reservoir. arch dermatol. 2006; 142:1344–1346. 27. bakotic bw, shavelson ds. the pathogeneis of nail unit “dystrophy.” podiatry management. 2006; 8:149-160. 28. szepietowski jc, reich a, garlowska e, et al. onychomycosis epidemiology study group. factors influencing coexistence of toenail onychomycosis with tinea pedis and other dermatomycoses: a survey of 2761 patients. arch dermatol. 2006; 142:1279-1284. 29. cozzani e, agnoletti af, speziari s, et al. epidemiological study of onychomycosis in older adults with onychodystrophy. geriatrics & gerontology international. 2016; 16:486–491. doi: 10.1111/ggi.12496. 30. nuvail [package insert]. charleston, sc: cipher pharmaceuticals; june 2012. 31. baker sj, hui x, and sanders v, et al. nail penetration of an2690: efficacy coefficient and effect of formulation. poster. anacor pharmaceuticals; 2006. http://investor.anacor.com/releasedetail. cfm?releaseid=285008. accessed july 8, 2016. 32. pillai r, korotzer a, olin jt. in vitro nail penetration of 14c-efinaconazole topical solution, 10%. supplement to the journal of clinical and aesthetic dermatology. 2014; 7:s15. 33. nasir a, goldstein b, van cleef m, swick l. clinical evaluation of a new topical treatment for onychomycosis. jdd. 2011; 10:1186-1191. 34. poulakos m, grace y, machin jd, dorval e. efinaconazole and tavaborole: emerging antifungal alternatives for the topical treatment of onychomycosis. journal of pharmacy practice. 2016; february 11 [epub ahead of print]. doi: 10.1177/0897190016630904. 35. elias pm, “barrier-repair therapy for atopic dermatitis: corrective lipid biochemical therapy,” expert review of dermatology. 2008; 3:441–452. 36. elias pm, hatano y, williams ml. basis for the barrier abnormality in atopic dermatitis: outside-insideoutside pathogenic mechanisms. journal of allergy and clinical immunology. 2008; 121:1337–1343. download a copy of this poster onto your mobile device at the qr code below: penetrate across poly-ureaurethane 16%. the diffusion cells had a 1.0 cm2 surface area and approximately 8 ml receptor volume. poly-ureaurethane 16% was applied to a 0.45µm nylon membrane and allowed to dry before use. efinaconazole 10% or tavaborole 5% was then applied to the poly-ureaurethane 16% coated membrane, and samples were pulled from the receptor chamber at various times. reverse phase chromatography was then used to assess the penetration of each active ingredient across the membrane. results: the flux and permeability of efinaconazole or tavaborole across poly-ureaurethane 16% were determined from efinaconazole 10% or tavaborole 5%, respectively. the flux and permeability of efinaconazole were determined to be 503.9 +/31.9 µg/cm2/hr and 14.0 +/0.9 nm/sec. the flux and permeability of tavaborole were determined to be 755.5 +/290.4 µg/cm2/hr and 42.0 +/16.1 nm/sec. conclusion: in addition to the treatment of onychoschizia, onychorrhexis, and other signs of severe dessication of the nail plate, a barrier that regulates towl should be considered in the management onychomycosis to address barrier dysfunction and to promote stabilization of the damaged nail. previously published flux values across the nail are reported to be 1.4 µg/cm2/day for efinaconazole and 204 µg/ cm2/day for tavaborole. these values are substantially lower than the herein determined flux for both molecules across poly-ureaurethane 16%. a comparison of the data suggests that poly-ureaurethane 16%, if used prior to efinaconazole or tavaborole, would not limit the ability of either active ingredient to access the nail, and therefore, would be unlikely to reduce their antifungal effect. onychodystrophy is inherent in, and often precedes onychomycosis, and consideration should be given for initiation of treatment in the same sequence: stabilizing and protecting the nail plate barrier primarily, and subsequently adding oral or topical antifungals after laboratory confirmation. future clinical studies will be needed to determine combination efficacy for in vivo use. chris g. adigun has served as a consultant for cipher pharmaceuticals. tracey c. vlahovic has served as a consultant for cipher pharmaceuticals. tergus pharma conducted the ivrt studies under contract for cipher pharmaceuticals. daniel b. ward, jr. and tuan a. elstrom are employees of cipher pharmaceuticals. disclosures figure 1. permegear vertical diffusion cell figure 2. average penetration profile of efinaconazole 10% across poly-ureaurethane 16% when dosed with 50 ul of efinaconazole 10% figure 3. average penetration profile of tavaborole across poly-ureaurethane 16% when dosed with 50 ul of tavaborole 5% efinaconazole 10%a tavaborole 5%b flux (µg/cm2/hr) 503.9 +/31.9 755.5 +/290.4 permeability (nm/sec) 14.0 +/0.9 42.0 +/16.1 table 1. flux and permeability of efinaconazole and tavaborole across poly-ureaurethane 16% avalues for efinaconazole are calculated based on linear regression using data from 1-6 hours. bvalues for tavaborole are calculated based on linear regression using data from 5-60 minutes. fpo have been reported to be as high as 57%,19-24 and with antifungal therapy alone (whether oral or topical), the underlying onychodystrophy that preceded or followed as a result of the fungal disease is not primarily addressed. in reality, onychomycosis is most often an end result of environmental conditions affecting the nails involving microtrauma, nail dystrophy (any alteration of nail morphology25), and a “pedal fungus reservoir” in a susceptible host. 26,27 although treating the fungi, if present, is necessary; addressing the underlying onychodystrophy, barrier dysfunction, and structural integrity of the nail plate are also of paramount importance. in fact, onychodystrophy, along with concomitant tinea pedis, are the precursors to onychomycosis.26-29 therefore, through in vitro release testing (ivrt) we sought to evaluate the penetration of efinaconazole 10% and tavaborole 5% across poly-ureaurethane 16%, which is fda cleared for onychodystrophy.30 poly-ureaurethane 16%, is a waterproof barrier that protects against the adverse effects of moisture, while preventing abrasion and friction,30 and now has been shown to allow in vitro penetration of efinaconazole or tavaborole to the nail when used in combination. poly-ureaurethane 16% has been previously described and employed successfully for the management of nail dystrophy including onychoschizia, onychorrhexis, and other signs of severe desiccation of the nail plate, collectively referred to as brittle nails. its ability to create a breathable shield on the nail by allowing oxygen permeability, but not water permeability,33 optimally regulates transonychial water loss (towl). because nail desiccation and onychodystrophy are contributing factors in onychomycosis, a waterproof barrier that protects the nail plate from wetting/ drying, fungal reservoirs, and microtrauma but also allows a topical antifungal to permeate its shield is potentially an advantageous combination. although formulated to penetrate the nail unit and work with the porosity and inherent electrical charge of the nail plate, the newer topical antifungals do not address nail plate damage that has been created from years of harboring a dermatophyte infection. the oral antifungals, terbinafine and itraconazole, likewise do not address this damage, and structural damage to the nail has been noted as a difficult complicating factor in the treatment and high recurrence rates of onychomycosis.24,34 poly-ureaurethane 16% has demonstrated its place in the management of the multifactorial disease of onychomycosis, through barrier protection and structural stabilization of a nail plate that has been compromised by onychodystrophy. primary therapy with poly-ureaurethane 16% aims to protect the diseased nail from further insult and desiccation, much as barrier formulations for compromised skin are foundational in promoting barrier repair.35,36 these ivrt study results reveal that this foundational barrier indeed allows penetration of the topical antifungal agents efinaconazole 10% and tavaborole 5%. dual therapy with poly-ureaurethane 16% and these agents or oral antifungal therapy, may have the potential to augment outcomes by stabilizing the compromised nail plate primarily and subsequently addressing fungus if present on laboratory analysis. up to 50% of cases of suspected onychomycosis are in fact due to onychodystrophy of other etiologies,1-4 and these patients will not benefit from anti-fungal therapy. for confirmed cases of onychomycosis, a goal of future combination studies with poly-ureaurethane 16% would be to evaluate rates of complete cure, which often lag behind mycological cure in trials. recurrence rates with continued weekly or bi-weekly use of poly-ureaurethane could also be assessed. future clinical studies of poly-ureaurethane 16% in combination with oral or topical antifungals are of course necessary to determine both in vivo efficacy and the validity of these assumptions. however, whether a nail has onychomycosis, or onychodystrophy due to other causes, barrier function and structural integrity are compromised in diseased nails,5,6 and should be addressed. methods the in vitro vertical diffusion cell model is a valuable tool for the study of drug release and penetration across specific test barriers. this model uses inert membranes, biological, or other barriers mounted in specially designed diffusion chambers allowing the system to be maintained at a controlled temperature, and was used in this experiment to evaluate the ability of efinaconazole 10% and tavaborole 5% to penetrate across polyureaurethane 16%. during the experiments, one coat of poly-ureaurethane 16% was applied evenly onto a 0.45µm nylon membrane with the applicator brush and allowed to dry prior to inserting the membrane on top of the receptor chamber. the donor chamber was then added to the apparatus, clamped in place securely, and the drug product administered on top of the poly-ureaurethane 16% within the donor chamber. a finite dose (50 µl) of either efinaconazole 10% or tavaborole 5% was applied, and drug penetration was measured by monitoring the appearance of the active component into the receptor chamber. the diffusion cells had a 1.0 cm2 surface area and approximately 8 ml receptor volume. samples were pulled from the receptor chamber at various times to assess the penetration of each active ingredient into the chamber by using reverse phase chromatography analysis. a diagram of a vertical diffusion cell is presented in figure 1. details are presented in the study design section. results efinaconazole 10% and tavaborole 5% penetrated across poly-ureaurethane 16%, and the flux and permeability are listed in table 1. appropriate method parameters were established to ensure the system was compatible with poly-ureaurethane 16% and to ensure adequate solubility of tavaborole and efinaconazole to maintain sink conditions throughout the experiment. the flux and permeability of efinaconazole 10% were determined to be 503.9 ± 31.9 µg/cm2/hr and 14.0+/-0.9 nm/ sec, respectively. the flux and permeability of tavaborole 5% were determined to be 755.5 ± 290.4 µg/cm2/hr and 42.0+/16.1 nm/sec, respectively. clinical implications flat ground joint fc17posterepihealthadigunefinaconazole.pdf observer-blinded, randomized study to determine the safety and efficacy of a silicone gel (recedotm gel) versus a gel containing onion extract (mederma® advanced scar gel) for the appearance and symptoms of surgical scars brian berman, md, phd, and mark nestor, md, phd center for clinical and cosmetic research, aventura, fl background • scarring can cause functional, cosmetic, and psychological morbidity1 • the clinical symptoms of scars include tenderness, discoloration, pruritus, and disfigurement • remedial treatments used for scars include surgery, laser therapy, steroid injections, and topical products such as onion extract gel and silicone gel2 • the use of silicone gel sheets for treating burns has revealed that skin grafts refrain from shrinking, while the area around the burns heals by epithelialization without hypertrophy3 • silicone gels and sheets are widely considered as first-line treatment for scars2 objectives • to evaluate the safety and efficacy, in terms of appearance and symptoms, of a 100% silicone gel (recedotm) compared with an onion extract-containing gel (mederma®) in adult subjects with postsurgical scars methods study design • randomized, evaluator-blinded, single-center, 16-week, activecomparator clinical study (figure 1) • all subjects had postsurgical scars that were 2 weeks to 4 months old • the initial treatment was applied to the affected scar at the baseline visit (day 0) by a designated device dispenser at that site who was not responsible for any subject or scar evaluations • all remaining treatments were applied by the subject • study visits were scheduled for baseline (day 0, first investigational product application), week 2, week 8, week 12 (end of treatment), and a final evaluation at week 16 (follow-up or early termination) figure 1. study design figure 1. study design 1:1 randomization day 0 baseline week 2 week 12 end of treatment 100% silicone gel twice daily (bid), n=24 onion extract-containing gel once daily (od), n=24 week 16 follow-up assessment follow-up week 8 study visits efficacy assessments • vancouver scar scale (vss) total score change from baseline to week 16 (including ratings of vascularity, pliability, and height, with scores of 0-3 for each; total potential score range was 0-9) • pain and itch scores change from baseline to week 16 (including ordinal ratings of 0-3 for each, and visual analog scale [vas] scores of 0-10 cm for each) • investigator’s and subject’s global assessment of scar treatment assessed at weeks 8, 12, and 16 (4-point assessments: 1=very good, 2=good, 3=moderate, and 4=unsatisfactory) • comparison between the 2 study groups in the subject’s global assessment of scar treatment at weeks 8, 12, and 16 safety assessments • adverse events (aes) and serious aes results baseline characteristics • subjects were well matched, with no significant differences between study groups for age, gender, ethnicity, race, or age of scar (table 1) • 1 subject in the onion extract-containing gel od group was lost to follow-up after the baseline visit table 1. baseline characteristics 100% silicone gel bid (n=24) onion extractcontaining gel od (n=24) gender, n (%) male female 13 (54.2) 11 (45.8) 10 (41.7) 14 (58.3) age, mean, years 61.7 60.5 ethnicity, n (%) hispanic or latino non-hispanic or -latino 6 (25) 18 (75) 5 (20.8) 19 (79.2) race, n (%) white hispanic black/african american 20 (83.3) 4 (16.7) 0 (0) 20 (83.3) 3 (12.5) 1 (4.2) age of scar, mean, days 45 52.4 efficacy evaluations vss score • the mean vss score increasingly improved (decreased) from baseline for both groups during the course of the study (figure 2) • the improvement was significantly greater for the 100% silicone gel bid group at week 2 (p<.01) and at the end of the study at week 16 (p<.05) compared with the onion extract-containing gel od group figure 2. improvement in mean vss score from baseline figure 2. improvement in mean vss score from baseline 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 week 2 week 8 week 12 week 16 m e a n c h a n g e f ro m b a s e li n e p<.05 p<.01 100% silicone gel bid onion extract-containing gel od pain and itch assessments • there was a significant reduction in subject-reported itch from baseline in the 100% silicone gel bid group but not in the onion extract-containing gel od group • mean vas scores – 100% silicone gel bid 0.3 at baseline 0 at week 16 (p<.02) – onion extract-containing gel od 0.2 at baseline 0.09 at week 16 • there were no significant differences between groups in subjectreported itch • there were no significant differences from baseline or between groups in subject-reported pain investigator’s global assessment of scar treatment • the mean change from baseline for the investigator’s global assessment of scar treatment increased significantly from week 2 to week 16 in both groups (p<.001 for each) (figure 3) figure 3. mean change from baseline in investigator’s global assessment of scar treatment figure 3. investigator’s global assessment of scar treatment 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 p<.001 m e a n c h a n g e f ro m b a s e li n e week 2 week 16 week 2 week 16 100% silicone gel bid onion extractcontaining gel od p<.001 subject’s global assessment of scar treatment • similar to the investigator’s global assessment, the mean change from baseline in the subject’s global assessment of scar treatment increased significantly from week 2 to week 16 in both groups (p<.04 for 100% silicone gel bid and p<.03 for onion extract-containing gel od) (figure 4) figure 4. mean change from baseline in subject’s global assessment of scar treatment figure 4. subject’s global assessment of scar treatment 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 p<.04 week 2 week 16 week 2 week 16 p<.03 m e a n c h a n g e f ro m b a s e li n e 100% silicone gel bid onion extractcontaining gel od safety evaluation • 10 subjects experienced aes during the study • the most common treatment-related ae was mild-to-moderate itching at the site of application, which was reported by 5 subjects (21.7%) in the onion extract-containing gel od group and 0 subjects in the 100% silicone gel bid group (p<.02) • application-site tenderness (recorded as burning, tingling, or sensitivity) occurred in 2 subjects (6.3%) • no serious aes occurred during the study conclusions • both the 100% silicone gel and the onion extract-containing gel were effective and safe in improving the appearance of postsurgical scars • as assessed by the vss, the 100% silicone gel bid was significantly more effective than the onion extract-containing gel od at improving postsurgical scars • the 100% silicone gel bid was better tolerated than was the onion extract-containing gel od, as nearly one-quarter of onion extract-containing gel od subjects had mild-tomoderate itching at the application site, versus no subjects receiving 100% silicone gel bid references 1. bock o, et al. arch dermatol res. 2006;297(10):433-438. 2. monstrey s, et al. j plast reconstr aesthet surg. 2014;67(8):1017-1025. 3. perkins k, et al. burns incl therm inj. 1983;9(3):201-204.disclosure: this study was funded by exeltis usa dermatology, llc. fc17posterexeltisbermanobserverblindedstudygel.pdf presented at: winter clinical dermatology conference–hawaii; january 18–23, 2019; koloa, hi. introduction • plaque psoriasis is a chronic, systemic inflammatory disease1 that requires long-term treatment and routine evaluations to monitor improvement.1,2 • many patients with psoriasis report that they are most bothered by symptoms in difficult-to-treat, highly visible, and pruritic areas, such as the scalp.3 • topical therapies can be difficult to apply to the scalp area and may feel greasy on the hair.3,4 • style (clinicaltrials.gov: nct03123471) is the first prospective, randomized, placebo (pbo)-controlled trial to evaluate the clinical efficacy and safety of apremilast, an oral phosphodiesterase 4 inhibitor indicated for the treatment of moderate to severe plaque psoriasis, in patients with moderate to severe psoriasis of the scalp. methods primary objective • to evaluate the efficacy of apremilast 30 mg twice daily (apr) vs. pbo in patients with moderate to severe plaque psoriasis of the scalp secondary objectives • to evaluate the efficacy of apr vs. pbo on whole body itch and scalp itch • to evaluate the safety and tolerability of apr in patients with moderate to severe plaque psoriasis of the scalp key inclusion criteria  • males or females ≥18 years of age • moderate to severe plaque psoriasis (psoriasis area and severity index [pasi] ≥12, psoriasis involved body surface area [bsa] ≥10%, and static physician global assessment [spga] ≥3 [moderate or greater]) • moderate to severe plaque psoriasis of the scalp (scalp pga [scpga] ≥3 [moderate or greater]; psoriasis-involved scalp surface area [ssa] ≥20%) • inadequate response or intolerance to ≥1 topical therapy for plaque psoriasis of the scalp study design • style was a phase 3, multicenter, randomized, double-blind, pbo-controlled study (figure 1). • patients were randomized (2:1) to apr or pbo for the double-blind pbo-controlled phase through week 16 and then continued or switched to apr for open-label treatment through week 32. – treatment groups were stratified by baseline scpga score (3 [moderate] or 4 [severe]). figure 1. study design placebo-controlled phase apremilast 30 mg bid open-label treatment phase screen* safety observation placebo apremilast 30 mg bid‡ ‒5 weeks week 16 week 32week 0 week 36 r a n d o m iz e 1: 2§ clinicaltrials.gov: nct03123471 *screening up to 35 days before randomization. §all doses were titrated over the first week of treatment. ‡at week 16, all placebo patients were switched to open-label apremilast 30 mg bid (with dose titration) through week 32. bid=twice daily. methods (cont’d) • the primary endpoint was the proportion of patients achieving scpga response (score of 0 [clear] or 1 [almost clear] with a ≥2-point reduction from baseline) at week 16 with apr vs. pbo. • secondary endpoints included the proportion of patients with ≥4-point improvement from baseline in whole body itch numeric rating scale (nrs) and scalp itch nrs scores at week 16 and at earlier visits (i.e., 12, 8, 4, and 2 weeks) and change from baseline in dermatology life quality index (dlqi) total score at week 16. statistical analyses • primary and secondary endpoints were analyzed in the intent-to-treat (itt) population, defined as all randomized patients. • analyses of the proportions of patients achieving the primary endpoint, whole body itch nrs response, and scalp itch nrs response were performed using the cochran-mantel-haenszel test with missing values imputed using the multiple imputation (mi) method; change from baseline in dlqi total score was analyzed using an analysis of covariance with missing values at week 16 imputed using the mi method. • the primary and secondary efficacy endpoints were hierarchically ranked for testing using the following sequence: primary endpoint; ≥4-point improvement from baseline in whole body itch nrs and scalp itch nrs, respectively, at week 16, week 12, week 8, week 4, and week 2; and change from baseline in dlqi total score at week 16. • for the primary and secondary endpoints, sensitivity analyses were also performed using the lastobservation-carried-forward (locf) and nonresponder imputation (nri) methods. • safety assessments were analyzed in the safety population, defined as all randomized patients who received ≥1 dose of study drug. results patients • a total of 303 patients were randomized, including 102 patients in the pbo group and 201 patients in the apr group. • in all, 252 patients completed the pbo-controlled phase (pbo, 84/102 [82.4%]; apr, 168/201 [83.6%]). • the most frequently cited reasons for discontinuation included withdrawal by patient (7.3%), adverse events (aes; 3.6%), and lack of efficacy (2.3%). • demographic and baseline clinical characteristics were generally comparable between the pbo and apr treatment groups (table 1). table 1. demographic and baseline clinical characteristics pbo n=102* apr n=201* age, mean (sd), years 46.7 (15.2) 47.0 (15.0) male, n (%) 62 (60.8) 125 (62.2) white, n (%) 75 (73.5) 154 (76.6) bmi, mean (sd), kg/m2§ 31.7 (7.2) 30.7 (7.1) psoriasis duration, mean (sd), years 14.8 (11.3) 15.7 (12.4) psoriasis-involved ssa, mean (sd), % 58.2 (26.4) 61.9 (27.2) scpga, n (%) moderate (3) 78 (76.5) 155 (77.1) severe (4) 24 (23.5) 46 (22.9) spga, n (%) moderate (3) 76 (74.5) 153 (76.1) severe (4) 26 (25.5) 48 (23.9) scalp itch nrs score, mean (sd) 6.7 (2.4) 6.6 (2.5) whole body itch nrs score, mean (sd) 7.2 (2.0) 7.2 (2.3) psoriasis-involved bsa, mean (sd), % 21.2 (14.8) 19.0 (10.8) dlqi total score, mean (sd) 12.6 (7.2) 12.6 (7.0) prior use of psoriasis medications phototherapy, n (%) 3 (2.9) 10 (5.0) conventional systemic therapy, n (%) 27 (26.5) 61 (30.3) biologic therapy, n (%) 31 (30.4) 53 (26.4) *the n reflects the number of patients as initially treated at week 0; actual number of patients available for each parameter may vary. §bmi is based on the last weight and height measurements taken before the randomization date. sd=standard deviation; spga=static pga. results (cont’d) scpga response • at week 16, significantly more patients treated with apr (43.4%) vs. pbo (13.8%; p<0.0001) achieved the primary endpoint, scpga response (score of 0 [clear] or 1 [almost clear] with a ≥2-point reduction from baseline) (figure 2). • results from sensitivity analyses comparing apr vs. pbo using locf and nri were consistent with the mi results for the primary endpoint (locf: 40.3% vs. 13.7%, p<0.0001; nri: 38.8% vs. 10.8%, p<0.0001). figure 2. proportion of patients achieving scpga response,* mi analysis 0 10 20 30 40 50 60 pa ti en ts ( % ) study week pbo (n=102) apr (n=201) 2 4 8 120 16 ‡‡ ‡ § * bars represent 2-sided 95% confidence intervals. scpga is evaluated on a 5-point scale ranging from 0 (clear) to 4 (severe), assessing the severity of erythema, scaling, and plaque elevation. *scpga response was defined as the proportion of patients achieving scpga score of 0 (clear) or 1 (almost clear) with ≥2-point reduction from baseline. *p<0.05. §p<0.001. ‡p<0.0001. scalp and whole body itch nrs • in patients treated with apr, the proportions who achieved ≥4-point improvement from baseline at week 16 in scalp itch nrs and whole body itch nrs scores were significantly greater vs. patients treated with pbo (figure 3). – a ≥4-point improvement from baseline on the scalp itch nrs was achieved in 47.0% of patients treated with apr vs. 21.3% receiving pbo (p<0.0001). – a ≥4-point improvement from baseline on the whole body itch nrs was achieved in 45.3% of patients treated with apr vs. 22.5% receiving pbo (p=0.0001). – statistically significant improvements with apr vs. pbo were observed on both itch nrs measures as early as week 2 (scalp: 26.0% vs. 11.5%, p=0.0025; whole body: 20.5% vs. 3.5%, p<0.0001). • similar results were obtained from sensitivity analyses comparing apr vs. pbo at week 16 using locf and nri for scalp itch nrs response (locf: 46.3% vs. 18.9%, p<0.0001; nri: 40.0% vs. 15.6%, p<0.0001) and whole body itch nrs response (locf: 44.3% vs. 20.2%, p<0.0001; nri: 40.0% vs. 19.1%, p=0.0005). figure 3. proportion of patients achieving ≥4-point improvement in a) scalp itch nrs score and b) whole body itch nrs score, mi analysis a. 0 10 20 30 40 50 60 pa ti en ts ( % ) pa ti en ts ( % ) study week pbo (n=90) apr (n=175) pbo (n=94) apr (n=185) 2 4 8 120 16 ‡‡ § ‡ || b. –10 0 10 20 30 40 50 60 study week 2 4 8 120 16 ‡ § § ‡ ‡ patients rated their scalp itch or whole body itch on a scale of 0 (no itch) to 10 (worst imaginable itch). analyses were based on patients in the itt population with baseline scalp itch nrs score ≥4 or whole body itch nrs score ≥4, as appropriate. error bars represent 95% confidence interval. ||p<0.01. §p<0.001. ‡p≤0.0001. results (cont’d) quality of life • mean change from baseline in dlqi total score over 16 weeks is presented in figure 4. • at week 16, least-squares mean improvement from baseline in dlqi total score was significantly greater with apr vs. pbo (−6.7 vs. −3.8, p<0.0001). figure 4. mean change in dlqi total score, data as observed –9 –8 –7 –6 –5 –4 –3 –2 –1 0 m ea n c ha ng e fr om b as el in e in d lq i t ot al s co re pbo (n=102) apr (n=201) 4 80 16 study week pbo, n 102 97 92 83 apr, n 201 192 184 169 mcid5 the dlqi total score has a possible range from 0 to 30, with higher scores corresponding to poorer health-related quality of life. error bars represent 95% confidence interval. safety • the most common aes reported with apr treatment from weeks 0 to 16 included diarrhea, nausea, headache, and vomiting (table 2). • the proportion of patients with serious aes during the pbo-controlled period was comparable between treatment groups (table 2). – one patient in the pbo group reported a serious ae of noncardiac chest pain, and 2 patients in the apr group reported serious aes (asthma [n=1] and chronic kidney disease [n=1]). the serious aes were not considered treatment related. • during the pbo-controlled period, 11 patients had ≥1 ae leading to drug withdrawal in the apr group (diarrhea [n=6], nausea [n=3], vomiting [n=3], agitation [n=1], anxiety [n=1], arthralgia [n=1], depression [n=1], dizziness [n=1], dysesthesia [n=1], headache [n=1], and joint effusion [n=1]) and 3 patients had ≥1 ae leading to drug withdrawal in the pbo group (depressive symptoms [n=1], nausea [n=1], and psoriasis [n=1]). table 2. overview of adverse events weeks 0 to 16 pbo n=102 apr n=200 patients n (%) n (%) ≥1 ae 49 (48.0) 133 (66.5) ≥1 serious ae 1 (1.0) 2 (1.0) ≥1 severe ae 2 (2.0) 5 (2.5) ae leading to drug withdrawal 3 (2.9) 11 (5.5) most common adverse events,§ n (%) diarrhea 11 (10.8) 61 (30.5) nausea 6 (5.9) 43 (21.5) headache 5 (4.9) 23 (11.5) vomiting 2 (2.0) 11 (5.5) conclusions • efficacy was demonstrated in this first prospective, randomized, pbo-controlled trial of apr in patients with moderate to severe plaque psoriasis of the scalp. • significantly greater improvements in scalp and whole body itch and quality of life were reported in patients treated with apr vs. pbo. • aes were consistent with the known safety profile of apr.6,7 references 1. baliwag j, et al. cytokine. 2015;73:342-350. 2. armstrong aw, et al. j am acad dermatol. 2017;76:290-298. 3. blakely k, et al. psoriasis (auckland). 2016;29:33-40. 4. schlager jg, et al. cochrane database syst rev. 2016;2:cd009687. 5. basra mka, et al. dermatology. 2015;230:27-33. 6. papp k, et al. j am acad dermatol. 2015;73:37-49. 7. paul c, et al. br j dermatol. 2015;173:1387-1399. acknowledgments the authors acknowledge financial support for this study from celgene corporation. the authors received editorial support in the preparation of this poster from amy shaberman, phd, of peloton advantage, llc, parsippany, nj, usa, sponsored by celgene corporation, summit, nj, usa. the authors, however, directed and are fully responsible for all content and editorial decisions for this poster. correspondence abby van voorhees – vanvooas @ evms.edu disclosures avv: abbvie, allergan, celgene corporation, derm tech, dermira, novartis, and valeant – honoraria for advisory board and/or consulting; merck – pension (ex-spouse). lsg: celgene corporation, leo pharma, novartis, pfizer, and stiefel/ glaxosmithkline – investigator and/or consultant. ml: mount sinai (which receives funds from boehringer ingelheim, celgene corporation, eli lilly, janssen/johnson & johnson, kadmon, medimmune/astrazeneca, novartis, pfizer, and vidac). bs: abbvie, amgen, astrazeneca, boehringer ingelheim, celgene corporation, dermira, eli lilly, forward pharma, janssen, leo pharma, maruho, medac, novartis, pfizer, stiefel/glaxosmithkline, sun pharma, and ucb – honoraria as a consultant and advisory board member; abbvie, amgen, celgene corporation, eli lilly, janssen, merck, novartis, and pfizer – payments (to the university of connecticut) as an investigator; corrona psoriasis registry – fees as a scientific director; abbvie and janssen – grant support (to the university of connecticut for fellowship program). st: no conflicts or potential conflicts of interest to disclose. ac: abbvie, amgen, astrazeneca, boehringer ingelheim, celgene corporation, dermira, eli lilly, janssen, maruho, novartis, pfizer, stiefel/glaxosmithkline, sun pharma, and ucb – investigator; celgene corporation – consultant hs: celgene corporation, janssen, lilly, and novartis – grants received as an investigator. yw, zz & mp: celgene corporation – employment. cl: abbvie, boehringer ingelheim, celgene corporation, eli lilly, janssen, merck, novartis, pfizer, sun pharma, and valeant – principal investigator/consultant. efficacy and safety of apremilast in patients with moderate to severe plaque psoriasis of the scalp: results of a phase 3, multicenter, randomized, placebo-controlled, double-blind study abby van voorhees1; linda stein gold2; mark lebwohl3; bruce strober4; charles lynde5; stephen tyring6; ashley cauthen7; howard sofen8; zuoshun zhang9; maria paris9; yao wang9 1eastern virginia medical school, norfolk, va, usa; 2henry ford health system, west bloomfield, mi, usa; 3icahn school of medicine at mount sinai, new york, ny, usa; 4university of connecticut, farmington, ct, usa, and probity medical research, waterloo, ontario, canada; 5lynde institute for dermatology, markham, ontario, canada; 6center for clinical studies, webster, tx, usa; 7midstate skin institute, ocala, fl, usa; 8dermatology research associates, los angeles, ca, usa; 9celgene corporation, summit, nj, usa copies of this poster obtained through the qr code are for personal use only and may not be reproduced without permission from the authors of this poster. presented at winter clinical dermatology conference 2019 | hawaii | 18–23 jan 2019 the efficacy of certolizumab pegol re-treatment on plaque psoriasis following a blinded treatment break: results from the cimpact trial m. lebwohl,1 v. piguet,2 h. sofen,3 a. blauvelt,4 c. arendt,5 s. kavanagh,6 m. boehnlein,7 m. augustin8 1icahn school of medicine at mount sinai, new york, ny; 2cardiff university and university hospital of wales, cardiff, uk; 3ucla, los angeles, ca; 4oregon medical research center, portland, or; 5ucb pharma, brussels, belgium; 6ucb pharma, raleigh, nc; 7ucb pharma, monheim, germany; 8ivdp, uke, hamburg, germany references 1. certolizumab pegol prescribing information. available at http://www.accessdata.fda.gov; 2. certolizumab pegol summary of product characteristics. available at http://www.ema.europa.eu/ ema; 3. lebwohl m. et al. j am acad dermatol 2018;79:266–76.e5. author contributions substantial contributions to study conception/design, or acquisition/analysis/interpretation of data: ml, vp, hs, ab, ca, sk, mb, ma; drafting of the publication, or revising it critically for important intellectual content: ml, vp, hs, ab, ca, sk, mb, ma; final approval of the publication: ml, vp, hs, ab, ca, sk, mb, ma. author disclosures ml: allergan, aqua, leo pharma, promius. employee of mount sinai which receives research funds from abbvie, amgen, boehringer ingelheim, celgene, eli lilly, janssen/johnson & johnson, kadmon, medimmune/astrazeneca, novartis, pfizer, valeant, vidac; vp: abbvie, almirall, celgene, janssen, novartis, pfizer, alliance, beiersdorf, biotest, dermal, eli lilly, galderma, genus pharma, globemicro, janssen, laroche-posay, l’oreal, leo pharma, meda, msd, novartis, pfizer, sinclair pharma, spirit, gsk, samumed, thornton ross, typham, ucb pharma; hs: abbvie, amgen, boehringer ingelheim, celgene, dermira inc., janssen, eli lilly, medimmune, novartis, pfizer, sun pharma, ucb pharma, valeant; ab: scientific adviser and/or clinical study investigator for abbvie, aclaris, akros, allergan, almirall, amgen, arena, boehringer ingelheim, celgene, dermavant, dermira inc., eli lilly and company, galderma, genentech/roche, gsk, janssen, leo, meiji, merck sharp & dohme, novartis, pfizer, purdue pharma, regeneron, revance, sandoz, sanofi genzyme, sienna pharmaceuticals, sun pharma, ucb pharma, valeant, and vidac. paid speaker for janssen, regeneron, and sanofi genzyme; ca, sk, mb: employees of ucb pharma; ma: abbvie, almirall, amgen, biogen, boehringer ingelheim, celgene, centocor, eli lilly, gsk, hexal, janssen, leo pharma, medac, merck, msd, mundipharma, novartis, pfizer, sandoz, ucb pharma, xenoport. acknowledgements the studies were funded by dermira inc. in collaboration with ucb pharma. ucb is the regulatory sponsor of cetolizumab pegol in psoriasis. we thank the patients and their caregivers in addition to the investigators and their teams who contributed to this study. the authors acknowledge bartosz łukowski, msc, ucb pharma, brussels, belgium for publication coordination, and joe dixon, phd, costello medical, cambridge, uk for medical writing and editorial assistance. all costs associated with development of this poster were funded by ucb pharma. objective • to assess the efficacy of certolizumab pegol in patients with moderate to severe plaque psoriasis who responded to initial treatment, relapsed during a treatment break, and were subsequently re-treated. background • plaque psoriasis (pso) is an immune-mediated, inflammatory disease; treatment options include systemic medication, phototherapy and biologic agents. • certolizumab pegol (czp) is a unique, fc-free, pegylated, anti-tumor necrosis factor (tnf) biologic, approved by both the fda and ema for the treatment of moderate to severe pso.1,2 • here, we assess efficacy of czp in patients with pso who responded to initial treatment, underwent a blinded treatment break, relapsed, and were subsequently re-treated. methods study design • patients were enrolled in the ongoing phase 3 trial cimpact (nct02346240); the full study design has been published previously.3 • patients included in this analysis received treatment according to figure 1. • we focus on czp-treated patients who achieved a 75% improvement from baseline in psoriasis area severity index (pasi 75) at the end of the initial period (week 16), were re-randomized to placebo every two weeks (q2w) for up to 32 weeks of double-blind maintenance treatment and subsequently relapsed (did not demonstrate a pasi 50 response [50% improvement from baseline]). • upon relapse, patients entered the 96-week open-label extension and received open-label czp 400 mg q2w. conclusions • following re-treatment with open-label czp 400 mg q2w, all patients re-achieved or improved upon their initial treatment response. • the results shown here indicate that czp may be an appropriate treatment option for patients who require a treatment break. • analyses using larger sample sizes would further validate these findings. aczp 400 mg loading dose at weeks 0, 2 and 4. bmi: body mass index; bsa: body surface area; czp: certolizumab pegol; dlqi: dermatology life quality index; il: interleukin; pasi: psoriasis area severity index; pga: physician’s global assessment; pso: plaque psoriasis; q2w: every two weeks; sd: standard deviation; tnf: tumor necrosis factor. table 1. demographics and baseline characteristics figure 2. mean absolute pasi through the initial treatment, withdrawal, and open-label re-treatment periods observed case (there were no missing data). standard deviations are shown in parentheses. all patients were re-randomized to placebo at week 16, and subsequently received open-label czp 400 mg q2w at relapse (ole week 0). acombined czp 200 mg q2w and czp 400 mg q2w; bczp 400 mg loading dose at weeks 0, 2 and 4. czp: certolizumab pegol; ole: open-label extension; pasi: psoriasis area severity index; q2w: every two weeks. patients • ≥18 years of age with pso for ≥6 months with pasi ≥12, ≥10% body surface area affected, physician’s global assessment ≥3 on a 5-point scale. • candidates for systemic pso therapy, phototherapy and/ or photochemotherapy. • exclusion criteria: previous treatment with czp, etn or >2 biologics; history of primary failure to any biologic or secondary failure to >1 biologic; erythrodermic, guttate or generalized pso types; current or history of chronic or recurrent viral, bacterial or fungal infections. figure 1. treatment arms included in this analysis patients were enrolled in the phase 3 cimpact trial. only study arms relevant to this analysis are shown. aloading dose of czp 400 mg q2w at weeks 0, 2 and 4; bdosing adjustment was at the investigator’s discretion based on pasi response. czp: certolizumab pegol; ld: loading dose; pasi: psoriasis area severity index; q2w: every two weeks. open-label treatmentinitial treatment period (double-blind) maintenance period (double-blind) n=165 randomization re-randomization 0 16 week 44403632 4828 96 week open-label czp 400 mg q2w < pasi 75 escape arm < pasi 75 escape arm czp 400 mg q2w placebo q2w (n=18)lda czp 200 mg q2w n=8 ≥pasi 75 n=10 ≥pasi 75 < pasi 50 < pasi 50 withdrawn czp 200 mg q2w open-label dose switchingbn=167 summary due to patient circumstances, physicians may recommend that individuals receiving biologic therapy take a treatment break. following re-treatment, all patients re-gained the same level of clinical response achieved after 16 weeks of initial treatment. we report the clinical outcomes of patients who:certolizumab pegol (czp) 1 fab’ had a successful initial treatment period with czp were withdrawn from treatment relapsed were re-treated with czp dosed at 400 mg every two weeks all czp (n=18) czp 400 mg q2w (n=10) czp 200 mg q2wa (n=8) age, years, mean (sd) 42.6 (13.1) 41.4 (8.7) 44.0 (17.7) male, n (%) 9 (50.0) 4 (40.0) 5 (62.5) bmi, kg/m2, mean (sd) 28.6 (4.1) 26.7 (1.8) 30.9 (5.0) prior biologic use, n (%) 6 (33.3) 4 (40.0) 2 (25.0) anti-tnf 0 0 0 anti-il-17 5 (27.8) 3 (30.0) 2 (25.0) anti-il-12/il-23 1 (5.6) 0 1 (12.5) pso duration, years, mean (sd) 23.0 (16.6) 19.4 (15.9) 27.6 (17.4) pasi, mean (sd) 23.4 (8.9) 24.0 (7.3) 22.6 (11.2) bsa affected, %, mean (sd) 33.3 (17.7) 34.3 (17.8) 32.0 (18.6) pga score, n (%) 3 (moderate) 15 (83.3) 8 (80.0) 7 (87.5) 4 (severe) 3 (16.7) 2 (20.0) 1 (12.5) dlqi, mean (sd) 11.8 (9.2) 13.8 (9.7) 9.3 (8.5) study assessments and statistical analyses • patients were assessed throughout the initial, maintenance and open-label periods for: – absolute pasi – pasi 75 and pasi 90 (90% improvement from baseline) • observed data are reported. • during re-treatment, time to achieve a 75% or 90% improvement in pasi from week 16 response was estimated using kaplan-meier analysis. results patient population • of the patients who were initially randomized to either czp 400 mg q2w or czp 200 mg q2w, achieved pasi 75 at week 16, and were re-randomized to placebo q2w for maintenance treatment, 18 relapsed and received open-label czp 400 mg q2w. • baseline demographics are shown in table 1. • mean pasi reduced rapidly over the initial 16 weeks of czp treatment (figure 2). • at week 16, in addition to pasi 75, 61% of patients (11/18) also achieved pasi 90. clinical response to withdrawal and re-treatment • following re-randomization to placebo, median time to relapse was 142 days (figure 2). • after 12 weeks of re-treatment with open-label czp 400 mg q2w, mean absolute pasi was comparable to that achieved after the initial 16 weeks (figure 2). • over the course of the re-treatment period and follow-up, all patients who had attained a pasi 75 or pasi 90 response at week 16 regained the same level of response. • a high proportion of patients achieved further improvements in pasi during re-treatment, compared to their week 16 score: – 83% of patients (15/18) achieved a further 75% improvement on their week 16 pasi in a median time of 127 days (95% confidence interval: 76–171) from re-treatment – 67% of patients (12/18) achieved a further 90% improvement on their week 16 pasi, in a median time of 169 days (95% confidence interval: 85–337) from re-treatment. 0 5 10 15 20 25 30 40 baseline week 16 ole week 0 ole week 12 time (weeks) m e a n a b so lu te p a s i double-blind czp treatment treatment withdrawal placebo q2w open-label re-treatment czp 400 mg q2w 24.0 (7.3) 23.4 (8.9) 22.6 (11.2) 2.8 (2.8) 2.5 (2.5) 2.2 (2.2) 16.7 (6.4) 16.1 (6.7) 15.5 (7.4) 5.4 (5.2) 4.8 (4.6) 3.9 (4.0) all czpa (n=18) czp 200 mg q2wb (n=8)czp 400 mg q2w (n=10) median time to relapse: 142 days (relapse) randomization group: powerpoint presentation winter clinical miami • feb. 17 – 20th, 2023 introduction • atopic dermatitis (ad) is a chronic, heterogeneous, relapsing-remitting disease characterized by intense itch and eczematous lesions. • two advanced systemic therapies are approved in adolescents with moderate-to-severe ad. • this study describes demographic characteristics, clinical and patient-reported outcomes in adolescents with moderate-to-severe ad in the target-derm ad registry stratified by advanced systemic therapy (ast) treatment status. 1 northwestern university feinberg school of medicine, chicago, il 2 target rwe, durham, north carolina, 3 leo pharmaceuticals, madison, new jersey, 4 rady children’s hospital, san diego, ca 5 university of california san diego, san diego, ca unmet needs of adolescents with moderate to severe atopic dermatitis in the target-derm registry paller a1, knapp k2, munoz b2, kalam a2, claxton a3, balu s3, schneider s3, eichenfield l4,5 aa conclusions • in adolescents with moderate-to-severe ad, nearly one-third did not progress to ast despite being eligible based on clinical and disease characteristics. • evaluation of prospective ast-treated showed more than 40% were not improved or had worsened at 12 weeks, on measures with n>=14. • although physician-reported outcomes with n>=14 were largely improved by 52 weeks, patient-reported quality of life (cdlqi), depression, and anxiety were unchanged or worsened in >50% of prospectively treated ast. • these real-world data suggest there is an unmet need to understand the reasons behind treatment inadequacies and potentially advancing more adolescents with moderate-tosevere ad who meet criteria to ast, and that more treatment options are needed for this population. inclusion/exclusion criteria • adolescent (12-17 years) at enrollment • moderate/severe ad defined by a score of 3 or 4 on validated investigator global assessment (viga-ad) • at least one follow-up visit post-enrollment • clinical trial patients excluded ast-treatment groups • ast-naïve (never ast-treated) • ast-treated: • retrospective (initiated ast prior to enrolling in targetderm ad) • prospective (initiated ast after enrolling in target-derm ad) • failed, stopped an ast and had either: a viga-ad increase or an ast-related adverse event methods • target-derm ad, launched in 2019, is an ongoing, longitudinal, observational study of patients managed in clinical practice at 48 community (n=23) or academic (n=25) sites in the united states; first enrolled patients jan. 25th, 2019, and the data herein spans the registry start date to november 11, 2022. • enrollment demographic, site, and clinical characteristics are analyzed descriptively • categorical variables are presented as numbers and percentages. continuous variables are shown as means with standard deviation, medians, minimum and maximum • asts considered in this study: dupilumab and upadacitinib • outcomes are only reported at each timepoint (enrollment, 12, 24, 36 and 52 weeks) if there were at least 14 patients with data on any given measure, at each timepoint longitudinal outcomes compared to enrollment, prospectively ast-treated patients were unimproved or worsened at 12 weeks on outcomes with n>=14, except where noted: • disease severity measures: viga-ad (43.9%), bsa (43.9%), viga x bsa (53.6%) • pros: promis depression (66.7%) and promis anxiety (60.0%) several pro measures persisted as unimproved or worse vs enrollment to 24, 36, 52 weeks, respectively • cdlqi (57.1%, 63.3%, and 55.0%) • promis depression (69.5%, 66.7%, and 66.7%) • promis anxiety (65.2, 66.6, and 63.0%) acknowledgements and disclosures: target rwe communities are collaborations among academic & community investigators, the pharmaceutical industry, and patient community advocates. target rwe communities are sponsored by target pharmasolutions inc (d.b.a., target rwe). the authors would like to thank all the investigators, participants, and research staff associated with target-derm ad. clinicaltrials.gov identifier: nct03661866. ap has been an investigator with: abbvie, anaptysbio, dermavant, eli lilly, incyte, janssen, krystal, regeneron, ucb; consultant with honorarium with: abbvie, acrotech, almirall, amgen, amryt, arcutis, arena, azitra, biocryst, biomx, boeringer ingelheim, botanix, bridgebio, castle biosciences, catawba, eli lilly, exicure, gilead, incyte, janssen, kamari, leo, novartis, pfizer, pierre fabre, rapt, regeneron, sanofi/genzyme, seanergy, ucb, union; on a data safety monitoring board with: abbvie, abeona, bausch, bristol myers squibb, galderma, inmed, novan; kk, bm, and ak are target rwe employees and may hold options. ac, sb, and ss are leo pharmaceutical employees and may hold options. eg is an employee of mount sinai and has received research grants research grants paid to her institution: boehringer ingelheim, leo pharma, pfizer, cara therapeutics, ucb, kyowa kirin, rapt, amgen, gsk, incyte, sanofi, bristol meyers squibb, aslan, regeneron, anaptysbio, concert, janssen and has been a consultant with: abbvie, almirall, amgen, aslan pharmaceuticals, astrazeneca, biolojic design, boerhinger-ingelhiem, bristol meyers squibb, cara therapeutics, connect, pharma, dbv technologies, eli lilly, emd serono, evidera, galderma, gate bio, genentech, incyte, inmagene, janssen biotech, kyowa kirin, leo pharma, merck, pfizer, q32 bio, rapt, regeneron, sanofi, sato, siolta, target, ucb, ventyx target-derm ad all patients n=2930 age 12-17 (n=364) study population n=128 • ast-naïve (n=40) • ast-treated (n=88)) ast-treated n=88 • moderate n=57 • severe n=31 ___________________________ • prospective n=50 • retrospective n=34 • failed n=4 ast-naïve n=40 • moderate n=28 • severe n=12 had 1+ follow-up visits (n=128) moderate or severe ad: viga-ad of 3 or 4 (n=196) figure 1. patient disposition results ast-usage • of 128 adolescents who met study criteria, 40 (31.3%) were ast-naïve, 34 (26.6%) were retrospectively-treated, 50 (39.1%) were prospectively-treated, and 4 (3.1%) were astfailed • all ast treatment was dupilumab, no upadacitinib usage reported. median days of dupilumab treatment was 500, 613, and 141 (retrospective, prospective and failed; p=0.01) • of 35 physicians, 25 (71%) were dermatologists and 7 (29%) allergists in this analysis. a dermatologist was the treating physician for ast-naïve (85%), ast-retrospective (94.1%), ast-prospective (96.0%) and ast-failed (100%). the remainder were treated by an allergist. differences were not significant (p=0.14) enrollment outcomes • at enrollment, there were no significant differences among treatment groups on demographic variables, physician specialty/site, viga-ad, and all pros. • significant enrollment differences were observed for median bsa (15% naïve, 18% retrospective, 40% prospective, 36% failed; p<0.01) and median viga-ad x bsa (45 naïve, 49 retrospective, 113 prospective, 124 failed; p<0.01) demographic/concomitant treatment variables • patient demographics • site and physician type • prior and concomitant topical ad therapy (any, calcineurin inhibitor, corticosteroid, phosphodiesterase) disease severity measures: • viga-ad (scores 0-4) • body surface area (bsa) (score %) • viga-ad x bsa (score 0-400) table 1. change over time definitions 0.0% 10.0% 20.0% 30.0% 40.0% 50.0% 60.0% 70.0% 80.0% 90.0% 100.0% f e m a le ( % ) h is p a n ic /l a ti n o n h w h it e n h b la ck a si a n o th e r/ n o t re p o rt e d m o d e ra te s e ve re n o n e a t a ll s m a ll m o d e ra te v e ry l a rg e e xt re m e ly l a rg e a ll e rg is t d e rm a to lo g is t m e d ic a id p ri va te u n in su re d a ca d e m ic c o m m u n it y sex race/ethnicity viga children's dlqi specialty insurance site type p e rc e n ta g e ast-naïve ast-retrospective ast-prospective 0 20 40 60 80 100 120 a g e ( y e a rs ) t b s a v ig a -a d s co re x b s a p o -s c o r a d p o e m p r o m is i tc h m o o d /s le e p p r o m is d e p re ss io n (t -s co re ) p r o m is a n xi e ty (t -s co re ) m e d ia n s co re ast-naïve ast-retrospective ast-prospective ast-failed not included due to small n figure 2. patient characteristics at enrollment by ast-status figure 3. disease severity and patient-reported outcomes at enrollment figure 4. duration of dupilumab therapy figure 5. percentage of prospectively ast-treated unchanged or worsening at 24, 36, 52 weeks* with n>=14 0 10 20 30 40 50 60 70 80 90 100 viga-ad n=41 bsa n=41 vxbsa n=41 cdlqi n=14 poem n=16 promis depression n=23 promis anxiety n=23 p e rc e n ta g e 24 weeks 36 weeks 52 weeks *12-week data not shown due to small n patient reported outcomes: • cdlqi: children’s dermatology life quality index (scores 0-30) • poem: patient-oriented eczema measure (scores 0-28) • po-scorad: patient-oriented scoring atopic dermatitis (scores 0-103) • patient-reported outcomes measurement information system (promis) depression (scores 41.0-79.4) and promis anxiety (scores 40.9-85.2) ast-failed not included due to small n 0 500 613 0 100 200 300 400 500 600 700 d a ys ast-naïve ast-retrospective ast-prospective p=0.0007 p=0.0013 ________________p=0.0005_________________ skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 301 brief article diffuse dermal angiomatosis of the breasts: a case series of 8 patients landon k. hobbs, bs1, darren guffey, md1, r. hal flowers, md1 1department of dermatology, university of virginia school of medicine, charlottesville, va diffuse dermal angiomatosis (dda) is a rare, benign, acquired reactive vascular disorder of the skin first described in 1994 most commonly affecting middle-aged females.1–3 as of early 2016, only 73 patients with dda had been reported to date.3 most case reports and series describe an association with hypoxic conditions such as vascular disease, calciphylaxis, and smoking, as well as other comorbid conditions including obesity and diabetes. dda can present as early as three years after significant weight gain.1,3–6 the condition has also been reported as more common in females with large pendulous breasts.1,3,4 dda typically presents with multiple erythematous to violaceous purpuric patches and plaques that may progress to necrosis and painful ulceration. although breast involvement was once considered rare in dda, recent studies suggest that the abstract background: diffuse dermal angiomatosis (dda) is a rare, reactive vascular disorder of the skin. association with vascular disease, smoking, and large pendulous breasts has been reported. no standard of care exists but benefit from various with medications and reduction mammaplasty has been reported. methods: we report a case of a 49-year-old obese female with a history of smoking who presented with dda that improved with smoking cessation and pentoxifylline prior to reduction mammaplasty. we also performed a retrospective chart review of all patients with dda seen at our institution between 2010 and 2020. results: eight female patients with dda affecting the breasts were evaluated at our institution. the mean age was 49.5 years. five of the patients noted symptoms at presentation. obesity was seen in 7 (87.5%) patients and 5 (63%) had a smoking history. there was no significant difference between symptomatic and asymptomatic groups in regard to age, t4=-0.63, p=0.56, but bmi trended higher in the symptomatic group, t6=2.27, p=0.06. three patients (38%) were noted to have fibromyalgia. all symptomatic patients saw improvement in their symptoms with treatments including reduction mammaplasty (1 patient), aspirin (1 patient), pentoxifylline (3 patients), smoking cessation (2 patients), and/or weight loss (1 patient). conclusions: our series is the second largest series of dda of the breasts and confirms many reported associations including obesity, smoking, and large pendulous breasts. we report the first known case of improvement with weight loss as a sole intervention, as well as identify a novel potential association between dda and fibromyalgia. introduction skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 302 breasts may be the most common site.3,4,7,8 histology is typically characterized by extensive proliferation of cd31 and cd34 positive endothelial cell proliferation around collagen bundles.2,3,5–7,9,10 although there is currently no standard of care, improvement in comorbidities including smoking cessation (if applicable), medical therapy (including corticosteroids, isotretinoin, aspirin, and pentoxifylline), and reduction mammaplasty have all been reported to be effective.1– 4,7,8,10 a 49-year-old female with a one pack-year history of smoking and obesity (body mass index 45) presented to clinic with a 10month history of painful plaques on bilateral breasts refractory to oral antibiotics. recent mammogram was normal. physical exam revealed large pendulous breasts, with prominent small telangiectasias and crusted ulcerations at the inferior aspects and an active ulcer on the left medial breast and scars from prior ulcers (figure 1). figure 1. right breast. prominent small telangiectasias, crusted ulcerations, and scars from prior ulcers. the patient reported allergy to aspirin, but was counseled on smoking cessation, referred for reduction mammaplasty, and started on pentoxifylline. at follow up three months later, her pain was drastically improved, all prior ulcers were healed, and she had no new ulcers. she had maintained abstinence from smoking but had only taken the pentoxifylline for two months due to cost. the patient eventually underwent bilateral reduction mammaplasty nine months later with full recovery and has not had any recurrence of her symptoms. after obtaining irb approval, we performed a retrospective chart review of all patients with dda seen at our institution between 2010 and 2020. we obtained a list of patients from the mc research analytics team, who did an electronic medical record (epic) search of “diffuse dermal angiomatosis.” we compiled data on demographics, clinical presentation, relevant co-morbidities including body mass index (bmi), smoking history, biopsy and lab results, and any treatments used with described outcomes. basic statistical analyses, including t-tests of unequal variance, were performed to further describe clinical characteristics including bmi and age. our initial review identified 17 patients with potential dda. nine patients were excluded due to a more likely alternative diagnosis or incomplete medical record. of the eight patients determined to have dda (table 1), all were female and five were symptomatic. all eight of the patients had dda of the breasts without involvement of any other location. the mean age was 49.5 years. case presentation methods results skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 303 table 1. clinical data of patients in the series patient demographics location of dda symptoms comorbidities bmi macromastia smoking history? (py at presentation) treatment and outcome 1 47f, white bilateral breasts pain, itching fm, hld, htn 33.1 yesa yes (10) repeat reduction mammaplasty → resolution 2 23f, black bilateral breasts pain, purulent drainage htn 50.3 yes yes (2) asa + pentoxifylline + smoking cessation → improvement 3 63f, white left breast pain, itching hld, htn, hypot, factor v leiden 70.4 yes yesb (33) weight lossc → resolution 4 51f, white bilateral breasts pain fm, hypot, cirrhosis 41.8 yes yes (35) pentoxifylline → improvement 5 49f, black bilateral breasts pain, purulent drainage ameloblastoma 45.7 yes yes (1) smoking cessation + pentoxifylline → improvementd 6 34f, white bilateral breasts 37.3 n/sa no none 7 63f, white bilateral breasts 33.5 n/s no none 8 66f, white bilateral breasts fm, hld, htn, hypot 25.7 n/s no none ahistory of prior breast reduction mammaplasty bpatient endorsed quitting smoking five years prior to presenting with dda cpatient’s lesions resolved as bmi decreased to 55.9 over two years dunderwent reduction mammaplasty for macromastia after dda had improved with smoking cessation and pentoxifylline asa – aspirin; bmi – body mass index; dda – diffuse dermal angiomatosis; f – female; fm – fibromyalgia; hld – hyperlipidemia; htn – hypertension; hypot – hypothyroidism; n/s – not specified; py – pack years. figure 2. a biopsy specimen from a patient in the series shows diffuse proliferation of capillary vessels in superficial and mid dermis between collagen bundles. (h&e, a: 10x; b: 20x) skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 304 the symptomatic cohort consisted of three white and two black females with a mean age of 46.6 years (sd=14.6). of these five patients, all had histories of obesity (bmi: m=48.3, sd=13.9), macromastia, and smoking. other common co-morbidities included hypertension (3 patients), hyperlipidemia (2 patients), fibromyalgia (2 patients), and hypothyroidism (2 patients). histologic specimens obtained from three symptomatic patients were consistent with dda with proliferation of superficial dermal vessels (figure 2). all patients saw improvement in their symptoms with reduction mammaplasty (1 patient), aspirin (1 patient), pentoxifylline (3 patients), smoking cessation (2 patients), and/or weight loss (1 patient). by last follow up, two of the four patients who were smoking at initial presentation had quit and had seen improvement in symptoms. in the asymptomatic group, all three were white females and the mean age was similar to that in the symptomatic group (54.3 ± 17.7, t4=-0.63, p=0.56). none of the patients had a history of smoking and bmi was lower than in the symptomatic group (bmi: m=32.2, sd=5.9, t6=2.27, p=0.06). patient 6 had undergone reduction mammaplasty years prior to being seen by dermatology; macromastia was not noted on dermatologic evaluation. biopsy was deferred in all asymptomatic cases and the diagnoses were made on clinical grounds alone. the patients remained clinically stable at last follow up. our series of eight patients represents the second largest cohort of patients with dda of the breasts, and third largest cohort of dda overall. the case series of 22 patients with dda of the breasts by reusche et al. is the largest to date.4 ten of their patients were diagnosed with dda clinically while twelve were confirmed with biopsy. other notable case series include: nine patients with concomitant calciphylaxis and dda but only one with involvement of the breasts5, seven patients with dda found in a case series of patients with calciphylaxis but none involving the breasts6, and five patients with dda of the breasts7. our case series confirmed many recognized characteristics and co-morbidities of dda. five of the eight (62.5%) patients experienced moderate-to-severe mastalgia. however, three patients (37.5%) were asymptomatic and not treated. in their series, reusche et al. similarly reported that 50% (11/22) had no documentation of treatment, including three patients with biopsy-confirmed dda.4 we also found high prevalence of comorbidities reported to be associated with dda including obesity (7/8), hypertension (4/8), and hyperlipidemia (3/8), very similar to prior reports. the difference in bmi between the symptomatic and asymptomatic groups was on the threshold of significance, likely affected by small sample size (n=8). all of the symptomatic patients in our series had a history of smoking, consistent with the reported association between dda and smoking. reusche et al. reported that 50% (11/22) patients identified as former or current smokers, with 58.3% (7/12) of patients with biopsy-confirmed dda having a smoking history. interestingly, all 3 asymptomatic patients were non-smokers. our confirmation of this association is notable as other series have contested the link between smoking and dda.4 prior to our series only a single patient with concomitant dda and fibromyalgia (fm) had been reported.1 our series of dda patients includes three patients diagnosed with fm discussion skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 305 (38%). the prevalence of fm in the united states is approximately 2%, thus it would not be unreasonable that this observation represents mere coincidence. however, the two disease processes may be linked by a common association, specifically obesity.11 alternatively, there may be an under recognition of dda as a diagnosis and significant cause of pain, which may be misattributed to fm by non-dermatologists. diffuse dermal angiomatosis occurring after reduction mammaplasty has been reported in five patients.2,4,7 reusche et al. reported one patient in their series with recurrence of macromastia and dda following breast reduction 30 years prior.4 adams et al. reported one case of dda in a female who had undergone reduction mammaplasty over 20 years prior.2 tollefson et al. reported three of five patients in their series had undergone breast reduction mammaplasty six weeks to 30 years prior to presenting with dda.7 in our series, two patients had undergone reduction mammaplasty years prior to developing dda. despite positive outcomes reported after reduction mammaplasty for patients with dda of the breasts, these reports of dda in patients with previous reduction mammaplasty suggest that the surgery is not curative since macromastia may still recur with time. the above literature provides support for the proposed causative association between macromastia and dda. macromastia is believed to result in tissue hypoxemia due to subclinical torsion, compression, and increased venous hydrostatic pressure.8 mastectomy may lead to full resolution4,9 but should be considered only after exhausting all more conservative approaches. we report the first case of dda that improved with weight loss as the primary intervention (patient 3, bmi decreased from 70.4 to 55.9). in the literature one patient with dda was reported to improve with the combination of weight loss and smoking cessation10, however another patient did not see substantial improvement despite reducing smoking and losing weight.8 furthermore, there are reports of dda presenting after or worsening with weight gain.1,3,4,8 in the series, we saw a trend of greater bmi among symptomatic patients compared to asymptomatic patients. higher bmi would likely result in larger pendulous breasts, a risk factor for dda of breasts. our observation of dda improving with weight loss as the sole intervention provides further evidence that obesity may be a primary etiologic factor in this rare disease. in summary, our series confirms many of the previously reported associations with dda including obesity, smoking, and large pendulous breasts. our series identified a novel potential association between dda and fibromyalgia which warrants further investigation. finally, we report the first known case of improvement of dda with weight loss as a sole intervention and recommend weight reduction be considered alongside other first line interventions for this rare disease. conflict of interest disclosures: none funding: the search by the mc research analytics team was supported in part by the national center for advancing translational sciences of the national institutes of health under award number ul1tr003015. this content is solely the responsibility of the author[s] and does not necessarily represent the official views of nih. corresponding author: landon k. hobbs, bs department of dermatology university of virginia school of medicine 1215 lee street charlottesville, va 22903 conclusion skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 306 phone: 434-924-5115 fax: 434-244-4504 email: lkh6k@virginia.edu references: 1. yang h, ahmed i, mathew v, schroeter al. diffuse dermal angiomatosis of the breast. arch dermatol. 2006;142(3). doi:10.1001/archderm.142.3.343 2. adams bj, goldberg s, massey hd, takabe k. a cause of unbearably painful breast, diffuse dermal angiomatosis. gland surg. 2012;1(2):132135. doi:10.3978/j.issn.2227-684x.2012.07.02 3. touloei k, tongdee e, smirnov b, nousari c. diffuse dermal angiomatosis. cutis. 2019;103(3):181-184. 4. reusche r, winocour s, degnim a, lemaine v. diffuse dermal angiomatosis of the breast: a series of 22 cases from a single institution. gland surg. 2015;4(6):554-560. doi:10.3978/j.issn.2227-684x.2015.08.02 5. prinz vavricka bm, barry c, victor t, guitart j. diffuse dermal angiomatosis associated with calciphylaxis. am j dermatopathol. 2009;31(7):653-657. doi:10.1097/dad.0b013e3181a59ba9 6. o’connor hm, wu q, lauzon sd, forcucci ja. diffuse dermal angiomatosis associated with calciphylaxis: a 5-year retrospective institutional review. j cutan pathol. 2020;47(1):27-30. doi:10.1111/cup.13585 7. tollefson mm, mcevoy mt, torgerson rr, bridges ag. diffuse dermal angiomatosis of the breast: clinicopathologic study of 5 patients. j am acad dermatol. 2014;71(6):1212-1217. doi:10.1016/j.jaad.2014.08.015 8. galambos j, meuli-simmen c, schmid r, steinmann ls, kempf w. diffuse dermal angiomatosis of the breast: a distinct entity in the spectrum of cutaneous reactive angiomatoses clinicopathologic study of two cases and comprehensive review of the literature. case rep dermatol. 2017;9(3):194205. doi:10.1159/000480721 9. frikha f, boudaya s, abid n, garbaa s, sellami t, turki h. diffuse dermal angiomatosis of the breast with adjacent fat necrosis: a case report and review of the literature. dermatol online j. 2018;24(5). accessed november 13, 2020. https://escholarship.org/uc/item/1vq114n7 10. azarfar a, bég s. diffuse dermal angiomatosis: case report of a distinct skin presentation. rheumatology. published online july 12, 2020:keaa311. doi:10.1093/rheumatology/keaa311 11. ursini f, naty s, grembiale rd. fibromyalgia and obesity: the hidden link. rheumatol int. 2011;31(11):1403-1408. doi:10.1007/s00296011-1885-z mailto:lkh6k@virginia.edu mailto:lkh6k@virginia.edu skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 667 brief article rapid efficacy of ixekizumab for pediatric acute generalized pustular psoriasis linda serrano, md1, valerie carlberg, md1,2, kristen holland, md 1,2 1 medical college of wisconsin, department of dermatology, milwaukee wi 2 children’s hospital of wisconsin, department of dermatology, milwaukee wi generalized pustular psoriasis (gpp) is an uncommon life-threatening subtype of psoriasis which is characterized by widespread sterile pustules overlying erythematous plaques. 1, 2 gpp has a female predominance with a median age of onset during the fifth decade of life, though earlier onset is noted in patients with a family history of psoriasis or homozygous mutation of interleukin (il) 36rn.3 il36rn and card14 are genes which encode proteins secreted by keratinocytes and are thought to contribute to the susceptibility of gpp. 1, 4 gpp accounts for 0.6% to 7% pediatric psoriasis cases , with a male predominance and onset between 3 and 16 years of age.3 gpp may be precipitated by infection, pregnancy, hypocalcemia associated with hypothyroidism, and drugs. 1 patients often present with features of sepsis and a coexisting infection which can lead to both diagnostic and therapeutic challenges.5 systemic manifestations of gpp include neutrophilic cholangitis, cholestasis, epigastric pain, otitis media, arthritis, interstitial pneumonitis, and renal failure.3 abstract introduction: generalized pustular psoriasis (gpp) is a rare, severe variant of psoriasis that is uncommon in pediatric patients and can be refractory to many therapies. ixekizumab, a monoclonal antibody that selectively inhibits interleukin 17-a, has been reported as safe and efficacious in patients with gpp, though minimal data exists on its use in the pediatric population. case presentation: a 17-year-old female with a history of alopecia areata and pustular psoriasis, on ustekinumab, was admitted for a severe pustular psoriasis flare with systemic symptoms including fever and tachycardia which progressed to erythroderma and required vasopressor support. after minimal improvement with 24 hours on broad-spectrum antibiotics, she received cyclosporine 5mg/kg/day. on day three of admission, and after two days of cyclosporine with minimal improvement, she received a 160 mg loading dose of ixekizumab. she defervesced and transferred out of the icu within 24 hours. she was successfully weaned off cyclosporine after her second dose of ixekizumab. she experienced no adverse reactions. discussion: generalized pustular psoriasis is less common and often more severe than plaque psoriasis, associated with increased morbidity and mortality in both pediatric and adult patients. clinical trials and case series have reported rapid and sustained improvement in patients with pustular psoriasis refractory to other therapies, though there is little data on the pediatric population. this case demonstrates the rapid efficacy of ixekizumab for severe erythrodermic pustular psoriasis in a pediatric patient, highlighting its use not only for refractory disease, but also as a rescue therapy in an emergent setting. introduction skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 668 retinoids, cyclosporine, and methotrexate, have shown efficacy in gpp, however, the use of these drugs presents a risk of toxicity. 2 we herein report a case of refractory gpp treated with ixekizumab, a high affinity monoclonal antibody that selectively inhibits il-17a, 6 with rapid improvement in a pediatric patient. a 17-year-old female with history of alopecia areata and pustular psoriasis, on ustekinumab, an il12 and 23 inhibitor, was admitted for a severe pustular psoriasis flare in the setting of dysuria and general malaise. she has a history of multiple pustular psoriasis flares in the past with known triggers including surgery and infections. she has been recalcitrant to many systemic therapies including methotrexate, cyclosporine, prednisone, infliximab, etanercept, adalimumab, and now ustekinumab. she had just returned from mexico during the peak of the covid-19 pandemic and her father had a current gastrointestinal illness. additionally, she had shaved her scalp 2 days prior to presentation, in anticipation of a hair prosthesis. examination was notable for innumerable pinpoint pustules on a background of erythema with overlying yellow crust on the scalp, trunk, and extremities including the palms and soles, with a notable predominance in the flexural surfaces (figure 1). she had patches of alopecia with superimposed pinpoint pustules (figure 2). there were no mucosal lesions and nikolsky sign was negative. she had fevers, tachycardia, abdominal pain, vomiting, diarrhea, dysuria, and diffuse adenopathy. figure 1. initial presentation of pustular psoriasis flare with pinpoint pustules on a background of erythema located on anterior neck and chest. figure 2. initial presentation of pustular psoriasis flare with pinpoint pustules on the scalp along with patches of alopecia areata. case report skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 669 laboratory studies were notable for leukocytosis with neutrophilic predominance, elevated sedimentation rate, c-reactive protein (crp), elevated procalcitonin (pct), elevated transaminases, and pyuria with trace bacteria on urinalysis. these findings were concerning for both a robust inflammatory response as well as an infectious trigger. she was admitted to the general medical floor with a plan for intravenous hydration, antibiotics, and immunosuppression; however, she decompensated in a matter of hours requiring transfer to the intensive care unit (icu) for vasopressor support. a skin biopsy was notable for a spongiotic dermatitis with a subcorneal pustule with a superficial and deep infiltrate including neutrophils and eosinophils consistent with pustular psoriasis. her skin examination progressed to erythroderma with generalized edema and lakes of pus most concentrated on the scalp though also present diffusely (figure 3). figure 3. progression to erythroderma day two of hospitalization. immunosuppression was held while infectious etiologies could be further assessed and while urgent approval of ixekizumab was sought. after minimal improvement with 24 hours of broadspectrum antibiotics, insurance barriers to inpatient biologic therapy, and negative infectious studies, she received cyclosporine 5mg/kg/day. on day three of admission, and after two days of cyclosporine with minimal improvement, she received a 160 mg loading dose of ixekizumab. she defervesced and transferred out of the icu within 24 hours. pustules desquamated, her erythema and edema decreased, and she was weaned off pain medication. she was discharged three days after starting ixekizumab and she was nearly clear at her one-week outpatient follow up (figure 4). she was successfully weaned off cyclosporine after her second dose of ixekizumab, four weeks later, and has remained clear. figure 4. near complete clearance of the scalp at one-week outpatient follow up. skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 670 generalized pustular psoriasis is less common and more severe than chronic plaque psoriasis and is associated with increased morbidity and mortality in pediatric and adult patients. our patient’s case was particularly challenging given her acute presentation which overlapped with septic shock. pct when used in combination with crp can be useful in differentiating bacterial infection from a gpp flare. a pct of less than 1.50 along and/or a crp of less than 46.75 can likely exclude a bacterial infection as the cause.5 our patient had a pct of 7.35 and a crp of 19.9. though the pct was suggestive of infection, we were comfortable with higher immunosuppression based on the crp being well below the reported cut off value for infection and given all her infectious studies came back negative. 5 we sought a rapid acting therapeutic with less immunosuppressive potential than traditional therapies, of which she had failed many in the past. ixekizumab is a high affinity monoclonal antibody that selectively inhibits interleukin 17-a.6 clinical trials and case series have reported rapid and sustained improvement in pustular psoriasis in patients refractory to other therapies, though there is little data on the pediatric population. 6-8 multiple cases of adolescent males with known deficiency of the interleukin il-36 receptor antagonist (ditra), characterized by fevers and pustular psoriasis flares, who were refractory to a variety of treatments such as acitretin, infliximab, cyclosporine, phototherapy, adalimumab, prednisone, ustekinumab, methotrexate, apremilast, and anikinara had a notable response to secukinumab, another antiil-17 monoclonal antibody. 9, 10 il-17a is highly expressed in skin of patients with gpp and reportedly plays a role in the activation of neutrophils10, 11. il-36 cytokines regulate th17 cytokines and correlate with increased levels of il-17. a pathomechanistic link between defective il36rn and th17 differentiation in ditra has been proposed though not yet completely understood.9, 10, 12 we present a 17-year old female with a severe gpp flare that rapidly improved with ixekizumab. ixekizumab along with other il17 inhibitors have been shown to be safe and effective in gpp and should be considered for treatment in refractory pediatric cases of pustular psoriasis such as this. further investigation is warranted in the use of il-17 inhibitors in gpp, especially in the pediatric population. conflict of interest disclosures: none funding: none corresponding author: linda serrano md medical college of wisconsin 8701 watertown plank rd milwaukee, wi 53226 phone: 414-955-3122 email: lserrano@mcw.edu references: 1. sugiura k. the genetic background of generalized pustular psoriasis: il36rn mutations and card14 gain-of-function variants. j dermatol sci 2014;74:187-92. 2. wang wm , jin hz. biologics in the treatment of pustular psoriasis. expert opin drug saf 2020;19:969-80. 3. hoegler km, john am, handler mz , schwartz ra. generalized pustular psoriasis: a review and update on treatment. j eur acad dermatol venereol 2018;32:1645-51. 4. marrakchi s, guigue p, renshaw br, puel a, pei xy, fraitag s et al. interleukin-36-receptor antagonist deficiency and generalized pustular psoriasis. n engl j med 2011;365:620-8. 5. wang s, xie z , shen z. serum procalcitonin and c-reactive protein in the evaluation of bacterial discussion conclusion skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 671 infection in generalized pustular psoriasis. an bras dermatol 2019;94:542-8. 6. okubo y, mabuchi t, iwatsuki k, elmaraghy h, torisu-itakura h, morisaki y et al. long-term efficacy and safety of ixekizumab in japanese patients with erythrodermic or generalized pustular psoriasis: subgroup analyses of an open-label, phase 3 study (uncover-j). j eur acad dermatol venereol 2019;33:325-32. 7. nagata m, kamata m, fukaya s, hayashi k, fukuyasu a, tanaka t et al. real-world singlecenter experience with 10 cases of generalized pustular psoriasis successfully treated with ixekizumab. j am acad dermatol 2020;82:75861. 8. saeki h, nakagawa h, nakajo k, ishii t, morisaki y, aoki t et al. efficacy and safety of ixekizumab treatment for japanese patients with moderate to severe plaque psoriasis, erythrodermic psoriasis and generalized pustular psoriasis: results from a 52-week, open-label, phase 3 study (uncover-j). j dermatol 2017;44:355-62. 9. cordoro km, ucmak d, hitraya-low m, rosenblum md , liao w. response to interleukin (il)-17 inhibition in an adolescent with severe manifestations of il-36 receptor antagonist deficiency (ditra). jama dermatology 2017;153:106-8. 10. molho-pessach v, alyan r, gordon d, jaradat h , zlotogorski a. secukinumab for the treatment of deficiency of interleukin 36 receptor antagonist in an adolescent. jama dermatol 2017;153:473-5. 11. yilmaz sb, cicek n, coskun m, yegin o , alpsoy e. serum and tissue levels of il-17 in different clinical subtypes of psoriasis. arch dermatol res 2012;304:465-9. 12. carrier y, ma hl, ramon he, napierata l, small c, o'toole m et al. inter-regulation of th17 cytokines and the il-36 cytokines in vitro and in vivo: implications in psoriasis pathogenesis. j invest dermatol 2011;131:2428-37. skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 438 brief articles adjunct treatment of recalcitrant hand plaques in nephrogenic systemic fibrosis after imatinib therapy james p. foshee, md1, thomas d. griffin jr. md2, kristin cam, md3, michael rivlin, md4, matthew keller, md2 1division of dermatology, university of arizona 2department of dermatology and cutaneous biology, thomas jefferson university hospital 3department of dermatology, mid-atlantic permanente medical group 4rothman institute orthopaedics, thomas jefferson university hospital nephrogenic systemic fibrosis (nsf) is a systemic fibrosing disorder most commonly identified in patients with impaired renal function. nsf presents with painful, sclerotic cutaneous plaques frequently distributed over the extremities and trunk, although visceral involvement has also been reported. [1] progressive involvement of peri-articular soft tissues may lead to joint contractures and significant functional limitation.[2] while the pathogenesis of nsf remains elusive, most cases occur in patients with renal dysfunction, particularly those exposed to gadolinium-based contrast agents (gbca) used in magnetic resonance imaging (mri).[2] gadolinium, poorly excreted in the setting of renal insufficiency, is hypothesized to deposit in tissues and induce fibrosis by stimulation of monocytes, macrophages, and fibroblasts.[3] imatinib mesylate (gleevec; novartis, basel, switzerland), a tyrosine kinase inhibitor, has demonstrated efficacy in the treatment of systemic sclerosing disorders, including introduction abstract nephrogenic systemic fibrosis (nsf) is a sclerotic disorder presenting with painful indurated plaques and skin thickening involving the trunk and extremities, which can lead to tethering and joint contractures. nsf most commonly affects patients with renal insufficiency who have been exposed to gadolinium. we present a case of nsf involving the bilateral hands, knees, and lower extremities developing over 10 years after gadolinium exposure. initial improvement was noted in the lower extremities after initiation of imatinib mesylate therapy, but recalcitrant, thickened hand plaques caused persistent pain and functional limitation. adjunct intralesional corticosteroid injections produced durable softening of the recalcitrant lesions with considerable functional improvement in hand mobility. based on our experience, intralesional corticosteroid injections appear to be an effective adjunct treatment in patients with incomplete response to anti-fibrotic therapies. skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 439 nsf, in small case series,[4-7] with notable softening and regression of fibrosis, likely related to interference with the pro-fibrotic tgf- and pdgf pathways.[5] however, despite promising results, refractory disease is common. we present a case of nsf with significant functional limitation refractory to systemic imatinib therapy successfully treated with intralesional corticosteroid injections. a 51-year old male presented with an approximately six-month history of thickened skin plaques beginning over the left palm, with subsequent spread to involve the bilateral palms, fingers, knees, elbows, and lower legs. these lesions were associated with pain and decreased range of motion, predominantly in the hands and knees, with occupational limitation (patient worked as a chef) and difficulty ambulating and riding a bicycle. his past medical history was notable for hemodialysis-dependent end-stage renal disease secondary to vesicoureteral reflux, with previous exposure to gadolinium-based contrast agents (gbca) >10 years prior to presentation. physical exam was remarkable for markedly firm, flesh colored plaques most notably on the thenar eminences and overlying the metacarpophalangeal (mcp) joints of the second, third, and fourth digits with extension to the proximal interphalangeal (pip) joints. (figure 1) flexion contractures of the pip and distal interphalangeal (dip) joints as well as limitations in finger extension were noted bilaterally. (figure 2, 3) the knees were similarly thickened, with indurated, “woody” plaques overlying both knees and pretibial shins. the modified rodnan skin thickness score (mrss),[8] a clinical tool commonly used in the evaluation and management of systemic sclerosis, was calculated to be 32. a skin biopsy of the palm demonstrated a fibrotic dermis, with increased mucin deposition and an increased number of cd34+ dermal fibrocytes suggesting a fibrosing dermopathy. tissue sent to the mayo clinic laboratory revealed a tissue gadolinium concentration of 3.9 mcg/g (ref. range < 0.5 mcg/g) by mass spectrometry. the patient was diagnosed with nephrogenic systemic fibrosis and started on 400 mg of daily imatinib, with rapid initial response most evident over the lower extremities and knees, and a reduction in mrss to 20. despite initial improvement, persistently thickened palmar nodules continued to cause pain and functional limitation even after five months of imatinib therapy. given his persistent acral disease and associated occupational limitation, we elected for adjunct therapy with intralesional triamcinolone acetonide injections. the procedure was initially poorly tolerated due to significant pain and difficulty injecting the solution into thick, fibrotic lesions, but 6 ml and 8 ml of 40 mg/ml intralesional triamcinolone acetonide were successfully injected across the palms and volar fingers by our hand surgeon under medial and ulnar nerve blocks during two separate sessions approximately four weeks apart. after intralesional corticosteroid injections, our patient noticed rapid improvement in occupational dexterity, with markedly improved finger flexion and extension bilaterally, along with notable reduction in size of his indurated hand lesions. (figures 2 and 3) the injections were well-tolerated, and no systemic or local corticosteroid adverse effects have been noted. he case report skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 440 continues to have excellent response after nine months of follow-up, and has not required additional intralesional therapy. figure 1. thickened palms and proximal digits before (a, b) and after (c, d) intralesional corticosteroid injection. there is notable thinning of the proximal digits and palms post-injection. figure 3. limitation in finger flexion before (a, b) and after (c, d) intralesional corticosteroid injections. notable improvement in range of motion of the finger joints post-injection. figure 2. flexion contractures of the bilateral fingers with thickening of the proximal digits and a positive “prayer sign”. skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 441 nephrogenic systemic fibrosis (nsf) is a sclerosing disorder most commonly affecting patients with impaired renal function who have been exposed to gadoliniumcontaining contrast media.[1, 2] while most cases of nsf develop within weeks to months after receiving gbca, our case presented with a relatively rapid course after over a decade of latency following gadolinium exposure. taken in conjunction with a recent report of nsf developing >10 years after gbca,[9] nsf should be a diagnostic consideration in sclerotic disorders in renal dysfunction patients, even with remote gbca exposure. intralesional corticosteroids have been well documented to induce collagen disintegration and reduction in fibroblast density and activity, in addition to their inherent anti-inflammatory properties.[10] while the use of intralesional corticosteroids to treat a sclerosing condition may not be entirely novel, the use of adjunct intralesional corticosteroids has not been previously documented as an effective treatment in cases of nsf refractory to systemic therapies. similar to other published reports,[5-7] our patient initially responded well to imatinib therapy, an efficacious treatment in fibrotic disorders.[4-8, 11] it should be noted, however, that while our patient had an initial reduction in mrss, it did not entirely normalize. this correlates with other published reports of persistent sclerotic disease despite systemic therapy.[6] since the mrss is a global assessment of skin fibrosis, it seems that complete resolution, or “normalization,” is unlikely given isolated areas of recalcitrance, particularly in patients presenting with widespread or severe fibrosis. with this in mind, the goal for nsf therapy, rather than “chasing” the mrss number, may instead be to target specific recalcitrant lesions in order to improve functional status. in our case, our patient demonstrated a durable response after nine months of follow-up, with limited local or systemic adverse effects and with dramatic functional improvement after two intralesional corticosteroid injections. with incomplete response to anti-fibrotic therapies being common, we believe our case highlights the utility of targeted intralesional corticosteroid injections as a useful adjunct strategy in the management of challenging sclerotic conditions. conflict of interest disclosures: none funding: none corresponding author: james p. foshee, md division of dermatology, university of arizona, tucson, arizona 7165 n. pima canyon dr. tucson, az 85716 tel: (520) 694-8888 email: jpfosheemd@gmail.com references: 1. cowper, s. e. et al. scleromyxoedema-like cutaneous diseases in renal-dialysis patients. lancet 2000; 356:1000–1001. 2. grobner, t. gadolinium--a specific trigger for the development of nephrogenic fibrosing dermopathy and nephrogenic systemic fibrosis? nephrol dial 2006; 21: 1104–1108. 3. wermuth, p. j. & jimenez, s. a. gadolinium compounds signaling through tlr 4 and tlr 7 in normal human macrophages: establishment of a proinflammatory phenotype and implications for the pathogenesis of nephrogenic systemic fibrosis. j immunol 2012; 189:318–327. 4. distler, j. h. w. & distler, o. tyrosine kinase inhibitors for the treatment of fibrotic diseases discussion mailto:jpfosheemd@gmail.com skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 442 such as systemic sclerosis: towards molecular targeted therapies. ann rheum dis 2010; 69: i48–51. 5. akhmetshina, a. et al. treatment with imatinib prevents fibrosis in different preclinical models of systemic sclerosis and induces regression of established fibrosis. arthritis rheum 2009; 60: 219–224. 6. elmholdt, t. r., pedersen, m., jørgensen, b., ramsing, m. & olesen, a. b. positive effect of low-dose imatinib mesylate in a patient with nephrogenic systemic fibrosis. acta derm venereol 2011; 91: 478–479. 7. kay j, high wa. imatinib mesylate treatment of nephrogenic systemic fibrosis. arthritis rheum 2008; 58: 2543–2548. 8. clements, p. j. et al. skin thickness score in systemic sclerosis: an assessment of interobserver variability in 3 independent studies. j rheumatol 1993; 20: 1892–1896. 9. larson kn, gagnon al, darling md, patterson jw & cropley tg. nephrogenic systemic fibrosis manifesting a decade after exposure to gadolinium. jama 2015; 151: 1117-20. 10. iudici, m., van der goes, m. c., valentini, g. & bijlsma, j. w. j. glucocorticoids in systemic sclerosis: weighing the benefits and risks a systematic review. clin exp rheumatol 2013; 31: 157–165. 11. spiera rf, gordon jk, mersten jn, et al. imatinib mesylate (gleevec) in the treatment of diffuse cutaneous systemic sclerosis: results of a 1-year, phase iia, single-arm, open-label clinical trial. ann rheum dis 2011; 70: 1003–9. skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 452 brief articles herbicide induced sclerodermoid reaction mimicking a photodistributed pattern kiley k. fagan, bs1, blake r. zelickson, md, phd2, robert b. skinner jr, md2, kristopher r. fisher, md2 1augusta university, department of dermatology, augusta, ga 2university of tennessee health science center, department of dermatology, memphis, tn a 69 year old caucasian man with type ii skin presented with a two month history of a rash on his trunk and upper extremities. the rash was asymptomatic and had not changed to his knowledge during this time period. review of systems was otherwise negative. the only medication the patient endorsed taking was benazeprilhydrochlorothiazide, which he had been taking for 2-3 years. physical examination revealed irregular hyperpigmented patches and slightly atrophic plaques in a sharply demarcated pattern on the back and upper extremities (figure 1), as well as faintly violaceous digitate patches on the abdomen. biopsies revealed no epidermal changes with thickened collagen bundles extending into the subcutaneous fat (figure 2), consistent with localized scleroderma. upon further questioning, the patient revealed that a few weeks prior to rash onset he recalled being sprayed accidentally with a herbicide spray, pasture pro, after a tube broke on his tractor. he was wearing thick slacks and a thin cotton t-shirt, which became sopping wet. he decided to continue working outside in the sunlight and took a shower later that evening. figure 1. clinical image: sharply demarcated hyperpigmented patches on back along the patient’s pant line. case report skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 453 figure 2. histopathology: hematoxylin-eosin staining, 40x: minimal epidermal changes with thickened collagen bundles spanning the reticular dermis in company with a sparse superficial and deep lymphocytic infiltrate containing plasma cells. morphea is an inflammatory process causing sclerotic skin changes of which many morphologies have been described. sclerodermoid reactions are a subtype of morphea and have been documented in the literature occurring after exposures including silica, solvents, hair dyes, epoxy resins, welding fumes, pesticides, herbicides, and plant solvents.1 herbicidal compounds known for causing sclerodermoid reactions include malathion, diniconazole, bromicil, diuron, and aminotriazole.2,3 the active ingredient in the herbicide pasture pro, 2,4dichlorophenoxyacetic acid (2,4 d), has not been reported to our knowledge as a cause of scleroderma. of note, this ingredient is a known component of the toxic herbicidal formulation, agent orange, which is also not documented in the literature as a cause of localized scleroderma.4 this case presented a diagnostic quandary due to its sharply demarcated pattern along clothing lines, mimicking photodistribution. for this unusual case, it was important to consider the broad differential diagnosis that can be formed via both clinical and histopathological findings. these include medication induced sclerodermoid reactions, sclerodermoid porphyria cutanea tarda, cutaneous t cell lymphoma, and atrophoderma of pasini and pierini. the patient had not taken any of the reported medications associated with these conditions5, and the diagnosis was made by a combination of this patient’s history and physical examination as well as histopathological evaluation. the most likely explanation for the unique distribution in this case is that due to the thin cotton t shirt, these areas were most exposed to the chemical as opposed to the skin protected under thick work pants. treatment for morphea is determined by the severity and extent of disease.6 this patient is currently being treated with triamcinolone 0.1% ointment and declined treatment with systemic medications. providers should be aware that sclerodermoid reactions induced by topical agents, such as herbicide sprays, can present in unusual patterns such as the pseudo-photodistribution in this case. the active ingredient 2,4 d also necessitates further investigation to determine the safety profile in relation to localized scleroderma. discussion skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 454 conflict of interest disclosures: none funding: none corresponding author: kiley fagan, bs 1004 chafee avenue, fh 100 augusta, ga 30904 tel: (770) 296-3795 email: kfagan@augusta.edu references: 1. rubio-rivas m, moreno r, & corbella x. occupational and environmental scleroderma. systematic review and meta-analysis. clinical rheumatology. 2017 mar;36(3):569-582. epub 2017 jan 14. pubmed pmid 28091808. 2. sozeri, b., gulez, n., aksu, g., kutukculer, n., akalin, t., & kandiloglu, g. (2012). pesticideinduced scleroderma and early intensive immunosuppressive treatment. archives of environmental and occupational health. https://doi.org/10.1080/19338244.2011.564231 3. dunnill, m. g. s., & black, m. m. (1994). sclerodermatous syndrome after occupational exposure to herbicides response to systemic steroids. clinical and experimental dermatology. https://doi.org/10.1111/j.13652230.1994.tb01262.x 4. veterans and agent orange: update 2014. (2017). military medicine. 182(7), 1619-1620. 5. ramdial pk, & naidoo dk. drug-induced cutaneous pathology. journal of clinical pathology. 2009;62(6):493-504. epub 2009/01/20. pubmed pmid: 19155238. 6. bielsa marsol i. update on the classification and treatment of localized scleroderma. actas dermosifiliograficas. 2013;104(8):654-66. epub 2013/08/13. pubmed pmid: 23948159. mailto:kfagan@augusta.edu https://doi.org/10.1111/j.1365-2230.1994.tb01262.x https://doi.org/10.1111/j.1365-2230.1994.tb01262.x kim papp, md, phd,1* jacek c. szepietowski, md, phd,2 leon kircik, md,3 darryl toth, md,4 michael e. kuligowski, md, phd, mba,5 may e. venturanza, md,5 kang sun, phd,5 eric l. simpson, md, mcr6 background ● atopic dermatitis (ad) is a chronic, intensely pruritic, inflammatory skin dermatosis that greatly impacts patients’ quality of life1,2 ● janus kinases (jaks) act downstream of proinflammatory cytokines and itch mediators involved in the pathogenesis of ad3,4 ● ruxolitinib cream is a topical selective inhibitor of jak1 and jak2 in development for the treatment of ad5 ● in a phase 2 study (nct03011892), ruxolitinib cream provided high rates of strength-dependent efficacy in patients with ad and a safety profile similar to vehicle6 objective ● to evaluate the efficacy and safety of ruxolitinib cream using pooled data from two phase 3 studies (truead1 [nct03745638] and true-ad2 [nct03745651]) in adolescent and adult patients with ad methods study design and patients ● eligible patients were aged ≥12 years with ad for ≥2 years, an investigator’s global assessment (iga) score of 2 or 3, and 3%–20% affected body surface area ● key exclusion criteria were unstable course of ad, other types of eczema, immunocompromised status, use of ad systemic therapies during the washout period and during the study, use of ad topical therapies (except bland emollients) during the washout period and during the study, and any serious illness or medical condition that could interfere with study conduct, interpretation of data, or patients’ well-being ● true-ad1 and true-ad2 had identical study designs (figure 1) – in both studies, patients were randomized (2:2:1) to either of 2 ruxolitinib cream strength regimens (0.75% twice daily [bid], 1.5% bid) or vehicle cream bid for 8 weeks of double-blind treatment – patients on ruxolitinib cream could subsequently continue treatment for 44 weeks; patients initially randomized to vehicle were re-randomized 1:1 to either ruxolitinib cream regimen figure 1. study design vehicle-controlled period (8 continuous weeks) long-term safety (treat as needed for 44 weeks) recurrence of lesions clearance of lesions patients initially randomized to rux remain on their regimen patients on vehicle re-randomized 1:1 to 0.75% rux or 1.5% rux 1.5% rux bid (n=~240 in each study) 0.75% rux bid (n=~240 in each study) patients randomized 2:2:1 vehicle bid (n=~120 in each study) rux* visits every 4 weeks week 52day 1 week 8 ad, atopic dermatitis; bid, twice daily; bsa, body surface area; rux, ruxolitinib cream. * patients will self-evaluate recurrence of lesions between study visits and will treat lesions with active ad (≤20% bsa). if lesions clear between study visits, patients will stop treatment 3 days after lesion disappearance. if new lesions are extensive or appear in new areas, patients will contact the investigator to determine if an additional visit is needed. assessments ● the primary endpoint was the proportion of patients achieving iga-treatment success (iga-ts; score of 0 or 1 with ≥2-grade improvement from baseline) at week 8 ● the main secondary endpoints were the proportion of patients achieving ≥75% improvement in eczema area and severity index score vs baseline (easi-75), the proportion of patients with a ≥4-point improvement in itch numerical rating scale (nrs4) score from baseline to week 8, and the proportion of patients with a ≥6-point improvement in the patient-reported outcomes measurement information system (promis) short form– sleep disturbance (8b) 24-hour recall score at week 8 ● an additional secondary endpoint was mean percentage change from baseline in scoring atopic dermatitis (scorad) score statistical analyses ● all analyses were conducted using the pooled data from both studies ● the primary and main secondary endpoints were analyzed by logistic regression ● all other secondary endpoints were analyzed using descriptive statistics ● the efficacy population consisted of 1208 patients (vehicle, n=244; 0.75% ruxolitinib cream, n=483; 1.5% ruxolitinib cream, n=481) ● the safety population consisted of all randomized patients (vehicle, n=250; 0.75% ruxolitinib cream, n=500; 1.5% ruxolitinib cream, n=499) 1k. papp clinical research and probity medical research, waterloo, on, canada; 2department of dermatology, venereology and allergology, wroclaw medical university, wroclaw, poland; 3icahn school of medicine at mount sinai, new york, ny, usa; 4xlr8 medical research and probity medical research, windsor, on, canada; 5incyte corporation, wilmington, de, usa; 6oregon health & science university, portland, or, usa *presenting author presented at the winter clinical dermatology conference january 16–24, 2021 results patients ● of 1249 patients randomized, 130 (10.4%) discontinued treatment during the 8-week vehicle-controlled period ● distribution of baseline demographics and clinical characteristics was similar across treatment groups (table 1) table 1. patient demographics and baseline clinical characteristics characteristic vehicle (n=250) 0.75% rux (n=500) 1.5% rux (n=499) total (n=1249) age, median (range), y 34.0 (12–82) 33.0 (12–85) 31.0 (12–85) 32.0 (12–85) 12–17, n (%) 45 (18.0) 108 (21.6) 92 (18.4) 245 (19.6) ≥18, n (%) 205 (82.0) 392 (78.4) 407 (81.6) 1004 (80.4) female, n (%) 159 (63.6) 304 (60.8) 308 (61.7) 771 (61.7) race, n (%) white 170 (68.0) 345 (69.0) 355 (71.1) 870 (69.7) black 61 (24.4) 118 (23.6) 113 (22.6) 292 (23.4) other 19 (7.6) 37 (7.4) 31 (6.2) 87 (7.0) region, n (%) north america 172 (68.8) 342 (68.4) 341 (68.3) 855 (68.5) europe 78 (31.2) 158 (31.6) 158 (31.7) 394 (31.5) bsa, mean ± sd, % 9.6±5.5 10.0±5.3 9.6±5.3 9.8±5.4 baseline easi, mean ± sd 7.8±4.8 8.1±4.9 7.8±4.8 8.0±4.8 ≤7, n (%) 127 (50.8) 249 (49.8) 244 (48.9) 620 (49.6) >7, n (%) 123 (49.2) 251 (50.2) 255 (51.1) 629 (50.4) baseline iga, n (%) 2 64 (25.6) 125 (25.0) 123 (24.6) 312 (25.0) 3 186 (74.4) 375 (75.0) 376 (75.4) 937 (75.0) itch nrs score, mean ± sd* 5.1±2.4 5.2±2.4 5.1±2.5 5.1±2.4 itch nrs score ≥4, n (%)* 159 (63.6) 324 (64.8) 315 (63.1) 798 (63.9) duration of disease, median (range), y 16.5 (0.8–79.1) 15.1 (0.1–68.8) 16.1 (0–69.2) 15.8 (0–79.1) facial involvement, n (%)† 93 (37.2) 195 (39.0) 197 (39.5) 485 (38.8) number of flares in last 12 mo, mean ± sd 7.3±25.7 5.2±6.7 6.0±17.6 5.9±6.5 bsa, body surface area; easi, eczema area and severity index; iga, investigator’s global assessment; nrs, numerical rating scale; rux, ruxolitinib cream. * data missing from 69 patients (vehicle, n=15; 0.75% rux, n=33; 1.5% rux, n=21). † patient-reported facial involvement. efficacy ● significantly more patients achieved iga-ts at week 8 with 0.75% and 1.5% ruxolitinib cream vs vehicle (44.7% and 52.6% vs 11.5%, respectively; both p<0.0001; figure 2) ● significantly more patients achieved easi-75 at week 8 with 0.75% and 1.5% ruxolitinib cream vs vehicle (53.8% and 62.0% vs 19.7%, respectively; both p<0.0001; figure 3) ● significantly greater itch reduction was observed within 12 hours of first 0.75% and 1.5% ruxolitinib cream application vs vehicle (mean change from baseline, –0.4 and –0.5 vs –0.1, respectively; both p<0.02; figure 4) ● significantly more patients demonstrated clinically meaningful improvement in itch (nrs4) and sleep disturbance (≥6-point improvement in promis sleep disturbance [8b]) with ruxolitinib cream vs vehicle (figure 5) – significantly more patients achieved nrs4 at week 8 with 0.75% and 1.5% ruxolitinib cream vs vehicle (41.5% and 51.5% vs 15.8%, respectively; both p<0.0001) – considerable improvement in promis 8b (≥6-point reduction) was achieved at week 8 with 0.75% and 1.5% ruxolitinib cream vs vehicle (20.9% and 23.8% vs 14.2%, respectively; both p<0.05) ● significant change from baseline in scorad score was achieved at week 8 with 0.75% and 1.5% ruxolitinib cream regimens vs vehicle (–62.9% and –67.3% vs –30.4%, respectively; both p<0.0001; figure 6) figure 2. proportion of patients achieving iga-ts pr op or tio n (s e) o f p at ie nt s ac hi ev in g ig ats , % † 0 10 20 30 40 50 60 0 2 4 8 time, wk vehicle (n=244) 0.75% rux (n=483) 1.5% rux (n=481) 26.2 45.1 52.6 **** 19.9 39.1 44.7 **** 3.7 6.1 11.5 iga-ts, investigator’s global assessment-treatment success; rux, ruxolitinib cream; se, standard error. **** p<0.0001 vs vehicle at week 8. † defined as patients achieving an iga score of 0 or 1 with an improvement of ≥2 points from baseline. patients with missing postbaseline values were imputed as nonresponders at weeks 2, 4, and 8. figure 3. proportion of patients achieving easi-75 pr op or tio n (s e) o f ea si -7 5 re sp on de rs , % † 0 10 20 30 40 50 70 60 0 2 4 8 time, wk vehicle (n=244) 0.75% rux (n=483) 1.5% rux (n=481) 4.9 12.3 19.7 28.0 47.0 53.8 33.9 54.7 62.0 **** **** easi-75, ≥75% improvement in eczema area and severity index score from baseline; rux, ruxolitinib cream; se, standard error. **** p<0.0001 vs vehicle at week 8. † patients with missing postbaseline values were imputed as nonresponders at weeks 2, 4, and 8. figure 4. change from baseline in daily itch nrs score m ea n ch an ge f ro m b as el in e in d ai ly it ch n rs s co re –3.5 –3.0 –2.5 –2.0 –1.5 0 –0.5 –1.0 b 12 h (p<0.02) 14 28 42 567 21 35 49 study day vehicle (n=244) 0.75% rux (n=483) 1.5% rux (n=481) –3.4 –3.0 –1.4 **** **** ** b, baseline; nrs, numerical rating scale; rux, ruxolitinib cream. * p<0.02 vs vehicle. **** p<0.0001 vs vehicle. figure 5. clinically meaningful improvement in itch nrs and promis sleep disturbance score (8b) pr op or tio n (s e) o f pr o m is 8 b re sp on de rs , % ‡ 0 10 20 30 40 pr op or tio n (s e) o f nr s4 r es po nd er s, % † 0 10 20 30 40 50 60 0 2 4 8 time, wk 0 2 4 8 time, wk vehicle (n=226) 0.75% rux (n=446) 1.5% rux (n=449) vehicle (n=158) 0.75% rux (n=313) 1.5% rux (n=307) 5.1 12.0 15.8 26.8 38.3 41.5 32.9 48.5 51.5 **** **** 7.5 9.7 14.214.1 18.2 20.9 16.3 19.6 23.8 * * nrs, numerical rating scale; promis, patient-reported outcomes measurement information system; rux, ruxolitinib cream; se, standard error. * p<0.05 vs vehicle at week 8. **** p<0.0001 vs vehicle at week 8. † patients in the analysis had an nrs score ≥4 at baseline. patients with missing postbaseline values were imputed as nonresponders at weeks 2, 4, and 8. ‡ defined as a ≥6-point improvement from baseline in the promis sleep disturbance score (8b). patients with missing postbaseline values were imputed as nonresponders at weeks 2, 4, and 8. figure 6. percentage change from baseline in scorad score m ea n (9 5% c i) pe rc en ta ge c ha ng e fr om b as el in e in s co ra d, % –70 –60 –50 –40 –10 0 –20 –30 0 2 4 8 time, wk vehicle (n=244) 0.75% rux (n=483) 1.5% rux (n=481) **** **** –15.3 –24.8 –30.4 –41.9 –56.4 –62.9 –47.4 –60.1 –67.3 rux, ruxolitinib cream; scorad, scoring atopic dermatitis. **** p<0.0001 vs vehicle at week 8. safety ● ruxolitinib cream was well tolerated and not associated with clinically significant application site reactions (table 2) ● no serious adverse events (aes) related to ruxolitinib cream were reported ● no treatment-emergent aes suggestive of a relationship to bioavailability were observed – ruxolitinib plasma levels were consistently low, with near-flat mean value curves throughout treatment table 2. treatment-emergent adverse events ae, n (%) vehicle (n=250) 0.75% rux (n=500) 1.5% rux (n=499) patients with teae 83 (33.2) 145 (29.0) 132 (26.5) treatment-related ae 28 (11.2) 23 (4.6) 24 (4.8) most common treatment-related aes* application site burning† 11 (4.4) 3 (0.6) 4 (0.8) application site pruritus† 6 (2.4) 4 (0.8) 0 discontinuation due to a teae 8 (3.2) 4 (0.8) 4 (0.8) serious teae‡ 2 (0.8) 4 (0.8) 3 (0.6) ae, adverse event; rux, ruxolitinib cream; teae, treatment-emergent adverse event. * occurring in >0.5% of the total patient population. † patient-reported tolerability was not lesion specific and was reported for all treated areas. ‡ no serious teaes were considered related to rux treatment. conclusions ● application of ruxolitinib cream brought about rapid (within 12 hours of initiation of therapy), substantial, and sustained reduction in itch ● ruxolitinib cream demonstrated superior efficacy vs vehicle for achieving iga-ts, easi-75, nrs4, a ≥6-point improvement in promis 8b, and change from baseline in scorad ● ruxolitinib cream demonstrated a dual mode of action: antipruritic and anti-inflammatory ● the ae profile was similar to vehicle; the rate of application site reactions was low ● these results demonstrate the potential of ruxolitinib cream as an effective and well-tolerated topical treatment for ad disclosures kp has received honoraria or clinical research grants as a consultant, speaker, scientific officer, advisory board member, and/or steering committee member for abbvie, akros, amgen, anacor, arcutis, astellas, bausch health/valeant, baxalta, boehringer ingelheim, bristol myers squibb, can-fite, celgene, coherus, dermira, dow pharmaceuticals, eli lilly, galderma, genentech, gilead, gsk, inflarx, janssen, kyowa hakko kirin, leo pharma, medimmune, meiji seika pharma, merck (msd), merck serono, mitsubishi pharma, moberg pharma, novartis, pfizer, prcl research, regeneron, roche, sanofi-aventis/genzyme, sun pharmaceuticals, takeda, and ucb. jcs has served as an advisor for abbvie, leo pharma, novartis, pierre fabre, menlo therapeutics, and trevi; has received speaker honoraria from abbvie, janssen-cilag, leo pharma, novartis, sanofi-genzyme, sun pharma, and eli lilly; and has received clinical trial funding from abbvie, almirall, amgen, galapagos, holm, incyte corporation, inflarx, janssen-cilag, menlo therapeutics, merck, novartis, pfizer, regeneron, trevi, and ucb. lk has served as an investigator, consultant, or speaker for abbvie, amgen, anaptys, arcutis, dermavant, eli lilly, glenmark, incyte corporation, kamedis, leo pharma, l’oreal, menlo, novartis, ortho dermatologics, pfizer, regeneron, sanofi, sun pharma, and taro. dt has served as an investigator for abbvie, avillion, amgen, arcutis, astellas, astion, boehringer ingelheim, celgene, dermira, ds biopharma, dow pharmaceuticals, eli lilly, f. hoffmann-la roche ltd, galderma, glaxosmithkline, incyte corporation, isotechnika, janssen, leo pharma, merck, novartis, pfizer, regeneron, and ucb biopharma. mek, mev, and ks are employees and shareholders of incyte corporation. els is an investigator for abbvie, eli lilly, galderma, kyowa hakko kirin, leo pharma, merck, pfizer, and regeneron and is a consultant with honorarium for abbvie, eli lilly, forte bio, galderma, incyte corporation, leo pharma, menlo therapeutics, novartis, pfizer, regeneron, sanofi genzyme, and valeant. acknowledgments support for this study was provided by incyte corporation. writing assistance was provided by mayur kapadia, md, an employee of icon (north wales, pa), and was funded by incyte corporation (wilmington, de). references 1. wei w, et al. j dermatol. 2018;45(2):150-157. 2. silverberg ji, et al. ann allergy asthma immunol. 2018;121(3):340-347. 3. bao l, et al. jakstat. 2013;2(3):e24137. 4. oetjen lk, et al. cell. 2017;171(1):217-228. 5. quintas-cardama a, et al. blood. 2010;115(15):3109-3117. 6. kim bs, et al. j allergy clin immunol. 2020;145(2):572-582. efficacy and safety of ruxolitinib cream for the treatment of atopic dermatitis: pooled analysis of two phase 3, randomized, double-blind studies to download a copy of this poster, scan code. the role of kappaand mu-opioid receptors in pruritus brian s. kim, md, mtr1, thomas sciascia, md2, gil yosipovitch, md3 1washington university, st. louis, mo, usa; 2trevi therapeutics, new haven, ct, usa; 3university of miami, miami, fl, usa introduction background • itch perception is transmitted from sensory neurons innervating the skin to the spinal cord; from there, spinal projection neurons relay signals to the brain, where itch sensation is perceived (figure 1) • a multitude of itch-inducing stimuli or pruritogens can trigger itch, including neurotransmitters, neuropeptides, proteases, and cytokines1,2; however, pathways that suppress itch remain poorly understood • chronic pruritus, defined as itch persisting for ≥6 weeks,3 may arise from a range of dermatologic, systemic, neuropathic, and psychological conditions1,4,5 and can be challenging to treat6 • although opioid receptors are typically associated with their role in pain signaling, recent studies have shed light on the emerging role of opioid receptors, particularly kappa-opioid receptors (kors) and mu-opioid receptors (mors), respectively, in suppressing and eliciting itch both in the periphery and more centrally7-10 objective • to summarize recent work supporting the role of kors and mors as potential therapeutic targets in the treatment of itch methods • a literature search of the pubmed database was conducted to identify english-language publications examining the role of opioid receptors in pruritus in the past decade (select references cited within identified publications were also incorporated) – search terms included “opioid receptor”, “kappa”, “mu”, “pruritus”, and “itch” • findings from relevant publications were summarized as a narrative review results itch signaling pathway and the role of opioid receptors • kappaand mu-opioid receptors have been identified throughout the itch signaling pathway, from skin, to spinal cord, to central nervous system (cns; figure 1)8,11,12 results (continued) figure 1. presence of mors and kors throughout the itch signaling pathway presence of opioid receptors mor kor skin brainspinalcord itch-selective unmyelinated c nerve fibers brain spinal cord histaminergic neuron nonhistaminergic neuron spinothalamic/ spinoparabrachial tract thalamus parabrachial nuclei neuropeptides t cell eosinophil mast cell neutrophil dermis epidermis skin itch stimuli dorsal root ganglion the illustration depicts that itch perception involves somatosensory drg neurons with axons extending to epidermal sensory terminals1,13; the drg contains the cell bodies of neurons that carry information from the periphery to the spinal cord. itch signals are ultimately carried to the thalamus, parabrachial nucleus, and possibly other brain centers by spinal projection neurons that cross the midline and join spinothalamic tracts.1,14 kors and mors have been identified in the skin, spinal cord neurons, and brain.8,11,12,15 drg, dorsal root ganglion; kor, kappa-opioid receptor; mor, mu-opioid receptor. reprinted from annals of allergy, asthma & immunology, vol 123, fowler e, yosipovitch g, chronic itch management: therapies beyond those targeting the immune system, pages 158-165, 2019, with permission from the american college of allergy, asthma & immunology. • following binding of an opioid to an opioid receptor, a cascade of intracellular changes occurs, resulting in reduced cellular excitability (figure 2a)16 • although activation of both kors and mors results in analgesia, other effects are distinct (figures 2b and 2c) – in particular, whereas activation of kors results in attenuation of itch7 in a variety of contexts, activation of mors is associated with increased itch17 (figures 2b and 2c) – in addition, there are reports of kor agonism resulting in suppression of inflammation8,11 • although the exact mechanisms are not established, in a preclinical model of atopic dermatitis, the dual kor agonist/mor antagonist nalbuphine decreased expression of the pruritogenic cytokine interleukin (il)-31, and increased expression of the anti-inflammatory cytokine il-1018 – in contrast to mor activation, neither mor blockade nor kor activation are associated with addiction,11 which has important therapeutic implications given concerns about opioid use • imbalances of activity across the kor and mor systems in the skin or cns are associated with severe chronic pruritus and are an active area of research for novel treatments15 figure 2. opioid receptors (a) intracellular changes occurring following the binding of an opioid agonist to an opioid receptor,16 (b) effects associated with mor activation, (c) effects associated with kor activation panel a is an illustration of opioid receptors, which are large membrane-bound proteins with the opioid-binding domain on the extracellular surface and 7 transmembrane domains.16,19 these receptors are “coupled” to an intracellular guanine nucleotide-binding protein (g protein) and thus are characterized as g-protein–coupled receptors.19 binding of an opioid agonist to a g-protein–coupled opioid receptor triggers a cascade of intracellular events. panels b and c illustrate the effects associated with activation of mors and kors, respectively.20 atp, adenosine triphosphate; camp, cyclic adenosine monophosphate; gdp, guanosine diphosphate; gtp; guanosine triphosphate; kor, kappa-opioid receptor; mor, mu-opioid receptor. panel a: adapted from pathan h, williams j, british journal of pain (volume 6, issue 1), pp. 11-16, copyright © 2012 by the british pain society. reprinted by permission of sage publications, ltd. preclinical models elucidate the effects of kor activation • kappa-opioid receptors are expressed on 2 different populations of dorsal root ganglion neurons associated with hair follicles in the epidermis8 – the endogenous kor agonist dynorphin reduces neuronal excitability8 – dynorphin is produced by inhibitory interneurons that modulate the neurons that respond to itch stimuli21 kors and mors as therapeutic targets • agents that activate kors have been shown to act within the peripheral nervous system and cns to attenuate itch7,8,18,22 – attenuation of itch has been demonstrated by kor agonists, including the endogenous ligand dynorphin and drugs like nalfurafine and difelikefalin • the association of mor activation with increased itching17 supports blockade of mors as another rational approach to inhibit itch – likewise, the mor antagonist naltrexone is employed as an antipruritic agent off-label23 • both kor and mor pathways are targeted with use of dual kor agonist/mor antagonists such as butorphanol and nalbuphine • opioid agents targeting kors and mors (figure 3) have demonstrated efficacy in a variety of chronic pruritic conditions, including uremic pruritus and prurigo nodularis23-28 figure 3. opioids targeting kors and/or mors in chronic pruritus mor antagonist naltrexone (oral) nalfurafine (oral) difelikefalin (iv) kor agonists dual mechanism mor antagonist/kor agonists butorphanol (intranasal) nalbuphine (oral)* *an oral formulation of nalbuphine is being developed for itch indications; an injectable formulation of nalbuphine is currently available in the us for pain-related indications. conclusions • kappaand mu-opioid receptors have emerged as important therapeutic targets in itch • notwithstanding these advances, the precise mechanisms by which kor agonists and/ or mor antagonists can be employed therapeutically remains an exciting area worthy of further investigation disclosures this study was sponsored by trevi therapeutics, inc, new haven, ct, usa. medical writing and editorial assistance were provided to the authors by peloton advantage, llc, an open health company, and funded by trevi therapeutics, inc. all authors met the icmje authorship criteria. no honoraria were paid for authorship. financial arrangements of the authors with companies whose products may be related to the present report are listed below, as declared by the authors. brian s. kim, md, mtr—consultant for abbvie, almirall, amagma, astrazeneca, boehringer ingelheim, cara therapeutics, daewoong pharmaceuticals, eli lilly, incyte, leo pharma, maruho, pfizer, regeneron, sanofi genzyme, trevi therapeutics. research grants for cara therapeutics and leo pharma. thomas sciascia, md—chief medical officer for trevi therapeutics; may own stock or stock options. gil yosipovitch, md—scientific advisory board member and consultant for pfizer, trevi therapeutics, kiniksa, regeneron, sanofi, galderma, novartis, eli lilly, leo pharma, bellus; received research funds from pfizer, sun pharma, kiniksa, leo pharma, and novartis. references 1. dong x, dong x. neuron. 2018;98(3):482-94. 2. acton d, et al. cell reports. 2019;28(3):625-39.e6. 3. ständer s, et al. acta derm venereol. 2007;87(4):291-4. 4. dhand a, aminoff mj. brain. 2014;137(pt 2):313-22. 5. yosipovitch g, bernhard jd. n engl j med. 2013;368(17):162534. 6. fowler e, yosipovitch g. ann allergy asthma immunol. 2019;123(2):158-65. 7. kardon ap, et al. neuron. 2014;82(3):573-86. 8. snyder lm, et al. neuron. 2018;99(6):1274-88.e6. 9. paul b-ql, et al. j am acad dermatol. 2004;50(3 suppl):p29. 10. yosipovitch g, et al. lancet. 2003;361(9358):690-4. 11. phan nq, et al. acta derm venereol. 2012;92(5):555-60. 12. peng j, et al. drug alcohol depend. 2012;124(3): 223-8. 13. potenzieri c, undem bj. clin exp allergy. 2012;42(1):8-19. 14. chen xj, sun yg. nature communications. 2020;11(1):3052. 15. fowler e, yosipovitch g. acta derm venereol. 2020;100(2):adv00027. 16. pathan h, williams j. br j pain. 2012;6(1):11-6. 17. tubog td, et al. j perianesth nurs. 2019;34(3):491-501.e8. 18. inan s, et al. eur j pharmacol. 2019;864:172702. 19. sehgal n, et al. pain physician. 2011;14(3): 249-58. 20. valentino rj, volkow nd. neuropsychopharmacology. 2018;43(13):2514-20. 21. pereira pj, lerner ea. neuron. 2014;82(3):503-5. 22. ross se, et al. neuron. 2010;65(6):886-98. 23. lee j, et al. ann dermatol. 2016;28(2):159-63. 24. kumagai h, et al. nephrol dial transplant. 2010;25(4):1251-7. 25. fishbane s, et al. kidney int rep. 2020;5(5):600-10. 26. fishbane s, et al. n engl j med. 2020;382(3):222-32. 27. khanna r, et al. j am acad dermatol. 2020;83(5):1529-33. 28. mathur vs, et al. am j nephrol. 2017;46(6):450-8. presented at the 2021 winter clinical dermatology conference–hawaii® gdp gtp activation of mor activation of kor atp camp agonist ca2+ k+ a. b. c. – – +α adenylate cyclase 7 transmembrane domains of opioid receptor g-protein respiratory depression pruritus constipation analgesia gi/0 dysphoriaanalgesia antipruritic effect reduced inflammation gi/0 skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 362 brief articles sterile neutrophilic folliculitis with vasculopathy in a young male patient with infective endocarditis carl barrick, do1, emily chea, bs2, naeha gupta, do1, richard mcclain, md3, stephen purcell, do3 1lehigh valley health network, allentown, pa 2philadelphia college of osteopathic medicine, philadelpha, pa 3advanced dermatology associates, ltd, allentown, pa a 34-year-old male with a past medical history of hepatitis c and intravenous (iv) drug abuse was admitted to the hospital with methicillin sensitive staphylococcus aureus (mssa) infective endocarditis complicated by septic pulmonary emboli, cervical osteomyelitis with soft tissue extension, bacteremia and acute kidney injury. on hospital day four, the patient abruptly developed a folliculitis-like rash on bilateral upper extremities for which dermatology was consulted. he denied any associated symptoms including itching, burning or pain. prior to consultation, he was treated with vancomycin, cefazolin, linezolid, and dialysis. on physical examination, the patient had pink to purple papules on the bilateral distal upper extremities (figure 1), some of which were eroded. distal lower extremities revealed scattered, non-blanching, bright pink macules. on re-examination three days later, the lesions on the bilateral upper extremities had evolved into larger, inflamed, firm, pink, centrally umbilicated, semi-translucent papules (figure 2), with few newly developed scattered similarly appearing lesions on the bilateral lower extremities. the previous macules on lower extremities persisted and were unchanged. seven days after initial presentation, the lesions began to spontaneously involute, leaving pink, crusted papules and macules without scars. the eruption continued to fade over the course of two weeks despite abstract sterile neutrophilic folliculitis with vasculopathy is a rare entity. histopathologically it is characterized by neutrophilic or suppurative and granulomatous folliculitis accompanied by a folliculocentric vasculopathy.1 it is a cutaneous manifestation of a systemic illness or infectious triggers. variations in clinical presentation are independent to the underlying medical condition.1 prompt identification may uncover an underlying systemic disease. the rarity of this clinical entity has led to a paucity of evidence regarding its etiology, diagnosis, and treatment recommendations. herein, we present a case of sterile neutrophilic folliculitis with vasculopathy in a 34-year-old male hospitalized for infective endocarditis. case report skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 363 continued fevers and persistently positive blood cultures. an extensive laboratory workup revealed a normal complete blood count and complete metabolic panel with exception of hemoglobin 9.9 g/dl (12.5-17), and creatinine 2.91 mg/dl (0.53-1.30). hematoxylin and eosin stains of punch biopsies obtained on initial presentation and three days later demonstrated folliculocentric neutrophilic dermatitis with perifollicular vasculitic changes (figure 3). a tissue culture from the second biopsy was negative for bacteria, deep fungal infection, and acid-fast bacilli. the histopathologic findings and negative cultures led to the final diagnosis of sterile neutrophilic folliculitis with perifollicular vasculopathy. figure 1. pink to purple papules with some erosion on the bilateral distal upper extremities. figure 2. inflamed, firm, pink, centrally umbilicated, semi-translucent papules on bilateral upper extremities. figure 3. folliculocentric neutrophilic dermatitis with perifollicular vasculitic changes, h&e 4x. sterile neutrophilic folliculitis with vasculopathy is a distinctive cutaneous pattern first described by magro and crowsen in 1998.1,2 this rare entity is characterized by a constellation of discussion skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 364 histopathological findings, which consist of neutrophilic or suppurative and granulomatous folliculitis in addition to a sweet’s-like vascular reaction or leukocytoclastic vasculitis. it is believed to be a reaction pattern to underlying systemic diseases such as behcet’s disease, reactive arthritis, inflammatory bowel disease, hepatitis b, various connective tissue diseases, and distant extracutaneous infections.1,3 though it is speculative, the association between sterile neutrophilic folliculitis with vasculopathy and an underlying systemic disease the exact etiology remains unclear. a prominent theory proposes that it is caused by an aberrant humoral or cellmediated immune response to various triggers, endogenous or exogenous, in a predisposed host.1 the follicle may serve as a site for cell-mediated immune responses due to enhanced hla-dr antigen expression, ϒ-δ t lymphocyte localization within the follicle, and increased langerhans cell concentration in the infundibular segment of the follicle, germinative sebaceous epithelium, and bulge area.1 potential endogenous antigens include heat shock proteins (hsp) and cytokeratin 18 in rheumatoid arthritis patients.1 whereas, exogenous stimuli include monosodium glutamate, ginger, upper respiratory infection pathogens, mycobacterium, hepatitis b, and drug therapy in individuals with dysregulated immune systems.1 lesions vary in presentation and appearance as folliculitis, vasculitis, or vesiculopustular or acneiform eruptions preferentially on the trunk, lower extremities, and upper extremities.1,2 constitutional symptoms such as fever, arthralgias, or malaise may accompany the lesions.1 while the histopathological and clinical appearance may suggest bacterial folliculitis, presence of constitutional symptoms should warrant other considerations of systemic diseases.1 histopathology reveals neutrophilic or suppurative and granulomatous folliculitis in conjunction with either: 1) perivascular and intramural neutrophilic infiltrate with leukocytoclasia and erythrocyte extravasation, demonstrating a sweet’s-like vascular reaction or 2) fibrinoid necrosis of vessel wall erythrocyte extravasation, demonstrating a leukocytoclastic vasculitis.1 tissue cultures and special stains fail to reveal an infectious pathogen.1 this case is presented to highlight the clinical presentation of sterile neutrophilic folliculitis. while there is information in the literature regarding its histopathology, there is a paucity of information on its clinical features. the case discussed illustrates a gentleman whose lesions were initially macular then evolved into centrally umbilicated, semi-translucent papules. the lesions then quickly involuted 7 days after initial presentation. interestingly, the patient continued to have constitutional symptoms and positive blood cultures while the lesions faded. the finding of sterile neutrophilic folliculitis with vasculopathy does not necessarily indicate the need for an exhaustive systemic disease workup.1 however, an infectious trigger or underlying systemic illness such as connective tissue disease, inflammatory bowel disease, or behcet’s disease should be considered. definitive treatment options have not been identified, however management of the underlying condition is the mainstay of treatment at this time. skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 365 conflict of interest disclosures: none funding: none corresponding author: emily p. chea, bs 4170 city avenue philadelphia, pa 19131 856-313-5530 emily.p.chea@gmail.com references: 1. magro cm, crowson an. sterile neutrophilic folliculitis with perifollicular vasculopathy: a distinctive cutaneous reaction pattern reflecting systemic disease. journal of cutaneous pathology. 1998;25(4):215-221. 2. patterson jw. weedon's skin pathology. 4th ed. london: churchill livingstone; 2016. 3. patterson jw. practical skin pathology: a diagnostic approach. philadelphia, pa: elsevier/saunders; 2013. skin july 2021 1288 proof returned skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 430 brief article nonavalent human papillomavirus vaccine as a treatment for recalcitrant warts in an adult with hiv michael tassavor, md1, peter hashim, md1, folawiyo o. babalola, bsa2, mehul bhatt, md1 1department of dermatology, icahn school of medicine at mount sinai hospital, new york, ny 2university of texas health science center at san antonio, san antonio, tx cutaneous warts are verrucous lesions caused by the proliferation of hpv in the epidermis. the lesions are infectious and are thus highly prevalent in the general population. the majority of those affected are children, but the lesions can be observed in all ages. immunocompromised patients have an increased risk of developing these lesions owing to their generalized increased susceptibility to infections. the consensus is that vaccinations, including the hpv vaccine, are primarily preventative measures. there have been limited studies on the use of hpv vaccinations as adjunct therapy to cutaneous warts in hiv patients. we report a case of an hiv patient successfully treated with hpv vaccination after multiple treatment failures. a 56-year-old white man with known hiv on treatment (undetectable viral load) presented to dermatology with a six-year history of palmoplantar warts. he reported failure of multiple rounds of cryotherapy, electrodessication and imiquimod cream under the supervision of his previous dermatologist. on physical exam, the patient had more than 21 verrucous plaques of various sizes on the soles of his feet bilaterally as well as the palmar surface of thumb of his left hand (figure 1). aside from the above, his medical history was significant for spondyloarthritis on sulfasalazine, and hcv, which resolved spontaneously in the distant past. he was tried on one intralesional candida injection and one round of cryotherapy with inadequate response. abstract cutaneous warts are seen in as many as a quarter of immunosuppressed patients. 1 cell-mediated immunodeficiency, as seen in hiv, is correlated with increased rates of palmoplantar warts. 2 these warts often cause discomfort, and can progress to verrucous carcinoma. as they can be resistant to traditional treatments like cryotherapy, patients must resort to more aggressive and invasive measures like intralesional bleomycin. in this case report, we present an immunocompromised patient with hiv successfully treated for his palmoplantar human papilloma virus (hpv) warts using the nonavalent hpv vaccine (gardasil 9tm, merck inc, kenilworth, nj, usa) after only marginal improvement with six treatments of bleomycin. introduction case presentation skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 431 figure 1. before treatment with bleomycin six treatments of intralesional bleomycin were attempted with mild improvement in the injected areas (figure 2). his pcp started him on the nonavalent hpv vaccine regimen before his seventh bleomycin injection, and by his eighth visit roughly two months later, he was noted to have a dramatic reduction in all lesions, including those that had not been injected with bleomycin. by his ninth visit three months after his first dose of the hpv series, his left sole had continued to clear rapidly, his right sole was clear except for a single small lesion, and his thumb had completely cleared (figure 3). despite the results, the patient desired to continue aggressive treatment and the few remaining lesions were injected with bleomycin once more. figure 2. after 5 injections of bleomycin, before first hpv shot common cutaneous warts are classically caused by hpv strains 1, 2, and 4, though it is known that immunosuppressed patients with plantar warts are more likely to have atypical hpv types like hpv-69. 3, 4 they are easily acquired via contact with the viral particle and spread through autoinoculation to different areas. treatment of verruca include cryotherapy, salicylic acid, imiquimod, 5-flourouracil, cantharidin, intralesional candida antigen, intralesional bleomycin, oral cimetidine, photodynamic therapy, and pulsed dye laser. none are universally effective. intralesional bleomycin is the treatment of choice at our institution for recalcitrant warts. this patient, with at least six years history of disease, had only marginal improvement with six previous injections before dramatically improving after a single shot of the vaccine, including areas we had not treated with bleomycin. this suggests the clinical improvement came from the vaccine rather than the bleomycin or spontaneous clearance. the vaccine series was started for prophylactic reasons and was only noted incidentally. this phenomenon has been reported before in immunosuppressed patients 5-8, but not yet in patients with hiv. a recent single center retrospective cohort study (n=16, two immunocompromised patients, one lost to follow up, the second deceased due to unrelated reasons) of recalcitrant warts showed nearly 50% response to hpv vaccination, comparable to conventional treatments. the authors noted no relationship in response to number of prior treatments, age, or anatomic location. 9 discussion skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 432 figure 3. after 8 injections of bleomycin, 3 months after first hpv shot while there are three fda approved vaccines, only the nonavalent gardasil 9 is currently available today in the united states, targeting hpv 6, 11, 16, 18, 31, 33, 45, 52 and 58. this vaccine does not cover the strains commonly associated with cutaneous warts, suggesting cross-reactivity with other hpv strains as has been shown before. 10 with an excellent safety profile, proven efficacy against nearly 90% of hpv associated cancer, and insurance coverage up to 45 years of age in adults, the nonavalent hpv vaccine may represent an early and relatively non-invasive adjunct to first line therapy. our patient improved after numerous failed trials with bleomycin, including in untreated areas, supporting vaccination as an effective adjunct therapy. as vaccination rates increase, it may also change annual incidence of these lesions. conflict of interest disclosures: none funding: none corresponding author: michael tassavor, md icahn school of medicine at mount sinai 325 w 15th st new york, ny 10011 phone: 212-367-0145 email: mtassavor2@gmail.com references: 1.wieland u, kreuter a, pfister h. human papillomavirus and immunosuppression. curr probl dermatol. 2014;45:154-65. doi:10.1159/000357907 2.leto m, santos júnior gf, porro am, tomimori j. human papillomavirus infection: etiopathogenesis, molecular biology and clinical manifestations. an bras dermatol. mar-apr 2011;86(2):306-17. doi:10.1590/s0365-05962011000200014 3.king cm, johnston js, ofili k, et al. human papillomavirus types 2, 27, and 57 identified in plantar verrucae from hiv-positive and hivnegative individuals. j am podiatr med assoc. mar 2014;104(2):141-6. doi:10.7547/0003-0538104.2.141 4.whitaker jm, palefsky jm, da costa m, king cm, johnston js, barbosa p. human papilloma virus type 69 identified in a clinically aggressive plantar verruca from an hiv-positive patient. j am podiatr med assoc. jan-feb 2009;99(1):8-12. doi:10.7547/0980008 5.ferguson sb, gallo es. nonavalent human papillomavirus vaccination as a treatment for warts in an immunosuppressed adult. jaad case rep. jul 2017;3(4):367-369. doi:10.1016/j.jdcr.2017.05.007 6.smith sp, baxendale he, sterling jc. clearance of recalcitrant warts in a patient with idiopathic immune deficiency following administration of the quadrivalent human papillomavirus vaccine. clin exp dermatol. apr 2017;42(3):306-308. doi:10.1111/ced.13038 7.silling s, wieland u, werner m, pfister h, potthoff a, kreuter a. resolution of novel human papillomavirus-induced warts after hpv vaccination. emerg infect dis. jan 2014;20(1):1425. doi:10.3201/eid2001.130999 8.kreuter a, waterboer t, wieland u. regression of cutaneous warts in a patient with wild syndrome following recombinant quadrivalent human papillomavirus vaccination. arch dermatol. oct 2010;146(10):1196-7. doi:10.1001/archdermatol.2010.290 conclusion skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 433 9.waldman a, whiting d, rani m, alam m. hpv vaccine for treatment of recalcitrant cutaneous warts in adults: a retrospective cohort study. dermatol surg. dec 2019;45(12):1739-1741. doi:10.1097/dss.0000000000001867 10.landis mn, lookingbill dp, sluzevich jc. recalcitrant plantar warts treated with recombinant quadrivalent human papillomavirus vaccine. j am acad dermatol. aug 2012;67(2):e73-4. doi:10.1016/j.jaad.2011.08.022 background ■ psoriasis (pso) is an inflammatory skin disease associated with a variety of psychiatric comorbidities such as anxiety and depression. ■ psychiatric comorbidities are associated with poor treatment adherence in pso patients, resulting in worse quality of life and increased economic burden.1 objectives ■ to estimate the healthcare utilization, direct costs, and indirect costs due to absenteeism or short-term disability associated with treated comorbid anxiety and/or depression among moderate-to-severe pso patients in the us methods study design and data sources ■ this was a retrospective cohort study of a commercially-insured population in the us. ■ data were extracted from the truven health marketscan® commercial claims and encounters (commercial) database and health and productivity (hpm) databases. — the commercial database provides detailed outcome measures including resource utilization and associated costs for healthcare services performed in inpatient and outpatient setting. — the hpm database contains workplan absenteeism and short-term disability data for a subset of enrollees in the commercial databases. study cohorts ■ moderate to severe pso: adults with ≥1 pso diagnosis plus ≥1 prescribed systemic or biologic pso medication (proxy for moderate-to-severe pso) from 1/1/2014 to 12/31/2014 — pso with treated anxiety/depression: patients with ≥1 diagnosis for anxiety and/or depression plus a prescription for anxiolytics, antipsychotics, or antidepressants filled within ±30 days of diagnosis — pso without treated anxiety/depression (controls): patients with neither anxiety/depression diagnosis nor prescription for anxiolytics, antipsychotics, or antidepressants — controls were randomly selected and matched 1:1 with patients with treated anxiety/depression on age, gender, health plan type, and region using the exact attribute matching method, to ensure comparability and reduce potential confounding biases. figure 1. patient selection patients ≥18 years old as of 1/1/2014 (n=27,706,785) continuous enrollment from 1/1/2014 to 12/31/2015 (n=11,223,477; 40.5%) ≥1 medical claim with diagnosis of pso and ≥1 non-topical systemic pso medication from 1/1/2014 to 12/31/2014 (n=17,955; 0.2%) ≥1 claim for diagnosis of anixety or depression plus a prescription of antianxiety agents, antipsychotics, or antidepressants �lled within ± 30 days of the diagnosis during 1/1/2014 to 12/31/2014 no claim for diagnosis of anxiety or depression, prescription of antianxiety agents, antipsychotics, or antidepressants during 1/1/2014 to 12/31/2014 (n=11,226) matched* pso with treated anxiety/depression (n=2,281) matched* pso without treated anxiety/depression (n=2,281) *the exact attribute matching method was applied to match the moderate to severe pso patients with vs without treated anxiety/ depression on a 1:1 ratio based on the following variables: age, gender, health plan type, residence region study measures ■ all-cause healthcare costs were defined as the sum of plan–paid and patientpaid costs, associated with any conditions incurred from inpatient admissions, emergency room visits, outpatient services, and outpatient pharmacy prescriptions. ■ pso-related costs included medical costs associated with a pso diagnosis and costs for pso-related biologics and other systemic medications. ■ all-cause and pso-related healthcare costs were compared between those with treated anxiety/depression and matched controls; in addition, costs due to both anxiety and depression, anxiety only, or depression only were also compared between the two cohorts. ■ lost time from short term disability was reported and indirect costs were estimated by multiplying lost days by 70%2 of the 2015 bureau of labor (bls) age-gender stratified daily wage rate for patients whose data could be linked with the hpm database. statistical analysis ■ the statistical significance of differences between the two cohorts was assessed using the t-test for continuous variables and chi-square or fisher's exact test for categorical variables. ■ generalized linear models with gamma distribution were used to estimate the incremental total costs attributable to treated anxiety/depression, after adjusting for demographic characteristics and comorbid conditions. ■ all statistical analyses were conducted using sas enterprise guide 7 (sas institute inc., cary nc). ■ a p-value of < 0.05 was defined as statistically significant. results demographic characteristics ■ a total of 4,562 commercially insured patients were included; 65% were female and the mean (±sd) age was 49 (±11) years (table 1). table 1. demographic characteristics of the study patients total pso n=4,562 matched pso with treated anxiety/depression (n=2,281) matched pso without treated anxiety/depression (n=2,281) age (mean, sd) 48.6 10.5 48.6 10.5 48.6 10.5 18-44 (n, %) 1,452 31.8% 726 31.8% 726 31.8% 45-64 3,110 68.2% 1,555 68.2% 1,555 68.2% 65+ 0 0.0% 0 0.0% 0 0.0% gender (n, %) male 1,614 35.4% 807 35.4% 807 35.4% female 2,948 64.6% 1,474 64.6% 1,474 64.6% region (n, %) northeast 796 17.4% 398 17.4% 398 17.4% north central 852 18.7% 426 18.7% 426 18.7% south 2,356 51.6% 1,178 51.6% 1,178 51.6% west 556 12.2% 278 12.2% 278 12.2% unknown 2 0.0% 1 0.0% 1 0.0% commercial plan type (n, %) hmo 418 9.2% 209 9.2% 209 9.2% ppo 3,022 66.2% 1,511 66.2% 1,511 66.2% pos 226 5.0% 113 5.0% 113 5.0% cdhp/hdhp 734 16.1% 365 16.0% 369 16.2% others* 146 3.2% 75 3.3% 71 3.1% unknown 16 0.4% 8 0.4% 8 0.4% cdhp: consumer-driven health plan; hdhp: high deductible health plan; hmo: health maintenance organization; ppo: preferred provider organization; pos: point-of-service plan *includes comprehensive/indemnity, exclusive provider organization, missing or unknown figure 2. three most frequently occurring comorbid conditions and concomitant medications used among study patients 39.2% 45.1% 44.4% 54.9% 46.5% 35.9% 33.8% 32.7% 30.3% 30.0% 31.0% 17.7% 0.0% 10.0% 20.0% 30.0% 40.0% 50.0% 60.0% psoriatic arthritis hypertension hyperlipidemia opioids respiratory medication anticholinergics matched pso with treated anxiety/depression matched pso without treated anxiety/depression §all p<0.01 clinical characteristics ■ compared with controls, pso patients with treated anxiety/depression had significantly higher overall burden of comorbidity, as measured by the quan-charlson comorbidity index (all p<0.01). ■ the pso with treated anxiety/depression cohort had a significantly higher percentage of patients with hypertension, hyperlipidemia, psoriatic arthritis (all p<0.01,) and use of concomitant medications (including opioids) (figure 2) than the control cohorts. all-cause and pso-related healthcare costs ■ on average, patients in the pso with treated anxiety and/or depression cohort incurred $10,419 (p<.01) higher unadjusted and $6,343 (p<.01) higher adjusted annual all-cause healthcare costs than matched pso controls; 88% of the difference was due to medical services and 12% due to prescriptions (table 2). — the all-cause difference was driven by a higher percentage of patients in the pso with treated anxiety/depression cohort who had hospitalizations, er visits, physician office visits, and other outpatient services (all p<.01). — pso related total healthcare costs were not significantly different between the pso with treated anxiety/depression group and the pso without treated anxiety/depression group. table 2. annual all-cause and pso-related healthcare costs of the study patients matched pso with treated anxiety/depression matched pso without treated anxiety/depression unadjusted mean difference p-value adjusted* mean difference p-value all-cause costs (mean, sd) total costs $50,300 $44,271 $39,881 $28,490 $10,419 <.01 $6,343 <.01 medical costs $18,696 $39,280 $9,531 $21,539 $9,165 <.01 $5,618 <.01 pharmacy costs $31,604 $24,533 $30,350 $21,971 $1,254 0.19 $414 0.67 pso-related costs (mean, sd) total costs $28,654 $24,632 $29,548 $21,373 -$894 0.48 -$1,393 0.28 medical costs $2,626 $13,789 $1,747 $8,410 $879 <.01 $366 0.01 pharmacy costs $26,028 $21,464 $27,801 $20,908 -$1,773 0.24 -$1,906 0.21 *the adjusted costs were estimated using glm with gamma distribution after adjusting the following variables: qci, other psychiatric conditions, psoriatic arthritis, rheumatoid arthritis, diabetes, hypertension, hyperlipidemia, obesity, thyroid disease. ■ compared with matched pso controls, pso patients with both treated anxiety and depression had $14,539 higher mean costs, pso patients with treated depression only had $10,262 higher mean costs and pso patients with treated anxiety only had $7,052 higher mean costs (all p<.01; figure 3). indirect healthcare costs ■ among those patients who could be linked with absenteeism records (n=99), pso patients with treated anxiety/depression had a mean of 22 (316 vs 294, p=.45) more work hours lost and $44 ($6,759 vs $6,714, p=.95) higher indirect costs due to absenteeism than matched pso controls. ■ among those patients who could be linked with the short term disability records (n=96), pso patients with treated anxiety/depression had a mean of 23 (63 vs 40, p=0.02) more lost days and $2,776 ($7,487 vs $4,711, p=0.01) higher indirect costs due to disability than matched pso controls. figure 3. healthcare costs stratified by patients with treated anxiety only, depression only, or both anxiety and depression pharmacy costs medical costs $13,547 $8,917 $32,154 $29,731 $20,208 $10,710 $31,360 $30,596 $22,312 $8,432 $31,344 $30,685 $0 $10,000 $20,000 $30,000 $40,000 $50,000 $60,000 anxiety only (n=713) controls (n=713) depression only (n=949) controls (n=949) anxiety and depression (n=619) controls (n=619) §all p<0.01 limitations ■ administrative claims data were collected for facilitating payment for healthcare services; therefore, definitive diagnoses are not available, and the true prevalence of treated anxiety and/or depression may be underestimated. ■ indirect costs may be also underestimated as presenteeism was not available in the database; however, indirect costs due to absenteeism and short-term disability were reported. ■ the study was composed of patients covered by commercial insurance; therefore, the results may not be generalizable to pso patients with other or no insurance coverage. conclusions ■ pso patients with treated anxiety/depression in a commercially insured population incur a substantial incremental economic burden over matched pso patients without treated anxiety/depression, primarily driven by greater use of medical services. ■ while further research is needed to confirm these findings, pso treatments that relieve psychiatric symptoms such as anxiety and depression may reduce incremental economic burden to benefit patients and the healthcare system. references 1. han c, lofland jh, zhao n, schenkel b. increased prevalence of psychiatric disorders and health care-associated costs among patients with moderate-to-severe psoriasis. j drugs dermatol. 2011 aug;10(8):843-50. 2. soliman am, surrey e, bonafede m et al. real-world evaluation of direct and indirect economic burden among ndometriosis patients in the united states. adv ther. 2018;35(3):408-423. this study was supported by janssen scientific affairs, llc economic burden of comorbid anxiety and depression among patients with moderate to severe psoriasis q. cai, ms, msph,1 a. teeple, mph,1 b. wu, ms,1 s. shrivastava, beng,2 e. muser, pharmd, mph1 1janssen scientific affairs, titusville, nj; 2mu-sigma, bengaluru, india acknowledgements study funded by and poster/editorial support provided by galderma laboratories, l.p., fort worth, tx a comprehensive analysis of the safety of a new range of injectable hyaluronic acid products for aesthetic indications david bank, md1; derek h. jones, md2; cindy wong, md*3; jay h. mashburn, phd4 1assistant clinical professor of dermatology, columbia presbyterian medical center and director, the center for dermatology cosmetic and laser surgery, mount kisco, ny; 2skin care and laser physicians of beverly hills, los angeles, ca; 3galderma, uppsala, sweden; 4galderma laboratories, l.p., fort worth, tx res.p-ma10367-09 *employee of galderma laboratories, l.p. at time of poster development introduction this review concerns the post-market safety experience of a range of hyaluronic acid (ha) fillers developed by q-med ab (uppsala, sweden), using optimal balance technology (obt)tm, known as xpreshan technologytm in the us (table 1).1 almost 1 million units were sold (ex-us) during the first 5 years on the market; this volume and duration of use allows for a thorough and accurate evaluation of the safety of these products to be conducted.2 subjects and methods data collection: • the safety dataset was compiled from post-market surveillance (pms) reports of adverse events (aes) received since the products were launched in 2011, including any cases reported in the literature • a total of 302 pms case reports were included in the analysis • available safety data obtained from sponsored clinical studies were also collected and reviewed data analysis: • reporting frequencies for pms reports were calculated based on the number of units of product sold and on the assumption that 1 unit was used per treatment • aes classified as related to treatment or as unassessable were considered to be potentially related aes and were included in the analysis potentially related adverse events with similar or associated preferred terms were grouped. results • pms case reports: of the total number of aes (from 302 case reports), 771 were classified as potentially related. overall reporting frequency: 0.033% for the period of 2011 to 2015, within a range between 0.026 to 0.035% per year five most common events were: swelling (0.016%), mass/induration (0.011%), pain and tenderness (0.007%), erythema (0.006%), and papules/nodules (0.006%) the rare reports of delayed onset events of nodules, swelling or inflammation responded to corticosteroids or hyaluronidase ten cases were reported as serious (ie, ischemia with or without necrosis, infection, swelling and nodules) • pms case reports, continued time to onset provided for 483 (63%) of the events · 68% of aes had a time to onset within 28 days after treatment, 77% within 60 days, and 90% within 120 days duration was available for 10% of events · among these events, 85% resolved within 28 days and 95% within 60 days information on the event outcome showed that 64% were resolved or resolving, but no information was available for 25% of these events • reporting frequencies of nodules, inflammatory reactions and granulomas for obt ha (table 2) • safety data from 7 sponsored interventional clinical studies and 1 observational study were reviewed studies; 638 subjects followed for 24 weeks to 18 months · no related serious adverse events adverse events reported · aes on 3 or more occasions in the entire study population: erythema, hematoma, swelling, pain, papules and telangiectasia · other events reported with lower occurrences were edema, induration, inflammation, pruritus, dermatitis, and skin tightness • the emervel french survey, a prospective real-practice descriptive study of 1,822 patients treated with multiple products over 15 months3 no saes reported immediate post-treatment assessment showed good local tolerability references 1. segura s, anthonioz l, fuchez f, et al. a complete range of hyaluronic acid filler with distinctive physical properties specifically designed for optimal tissue adaptations. j drugs dermatol. 2012 jan;11(1 suppl):s5-s8. 2. data on file, galderma laboratories, l.p. 3. farhi d, trevidic p, kestemont p, et al. the emervel french survey: a prospective real-practice descriptive study of 1,822 patients treated for facial rejuvenation with a new hyaluronic acid filler. j drugs dermatol. 2013 may;12(5):e88-e93. 4. fda maude database. summary ■ there is now a 5-year safety experience to give confidence for use of the obt range (known as xpreshan technologytm in the us) of ha fillers ■ there are no new unexpected aes compared to other established fillers on the market ■ late onset-aes that are difficult to treat are very rare ■ the insight gained from real-world practice is that the use of hyaluronidase with or without corticosteroids can treat rare events such as granulomas, delayed onset nodules, and swelling table 1. hyaluronic acid-based injectable filler product range: original and rebranded names new name original name unit volumes restylane® refyne emervel classic lidocaine 1 ml restylane® defyne emervel deep lidocaine 1 ml restylane® kysse emervel lips lidocaine 1 ml restylane® volyme emervel volume lidocaine 1 ml 2 ml restylane® fynesse emervel touch 1 ml adverse events emervel (obt ha)2,4 reporting rate (%), (n = 922,594) jan 1, 2011 to dec 31, 2015 swelling/edema 0.0163 inflammatory reaction 0.003 papules/nodules 0.006 granuloma 0.00043 hypersensitivity 0.001 ischemia/necrosis 0.001 table 2. reporting frequencies of selected adverse events table 3. adverse events reported after 28 days2,4 adverse events number typical outcome if available granuloma 5 typically resolved with hyaluronidase monotherapy or combination therapy nodules 13 typically resolved with hyaluronidase monotherapy or combination therapy swelling with or without inflammation 6 typically resolved with hyaluronidase monotherapy or combination therapy swelling preceded by infective episode 4 recovered after antibiotics fc17postergaldermabankcomprehensiveanalysisnewrange.pdf objective • in this post hoc analysis of a 52-week open-label study (nct02462083),1 we assessed the efficacy and safety of once-daily halobetasol propionate (0.01%) and tazarotene (0.045%) lotion (hp/taz) in 550 participants with psoriasis stratified by baseline signs and symptoms of disease conclusions • long-term use of hp/taz was generally associated with treatment success regardless of baseline symptom severity, and no new safety signals emerged over 52 weeks • participants with mild baseline symptoms were less likely to experience local skin reactions postbaseline compared with participants with more severe baseline symptoms • evaluation of patients’ baseline itch, dryness, and stinging/burning may help predict outcomes of hp/taz treatment • clinicians can use this information to counsel patients regarding treatment expectations when initiating hp/taz synopsis • topical psoriasis treatments may be used as monotherapy for mild disease or as adjunct therapy for more severe disease2 • fixed-combination halobetasol propionate (0.01%) and tazarotene (0.045%) lotion (hp/taz) is approved for treatment of plaque psoriasis in adults3 • given that patients’ experiences with psoriasis differ greatly, further consideration and assessment of the utility of hp/taz in patients with varying symptom severity is warranted methods • all participants received once-daily hp/taz for 8 weeks (figure 1) • at week 8, participants who achieved the primary endpoint of treatment success (defined as investigator’s global assessment [iga] of clear [0] or almost clear [1]) stopped hp/taz and were reevaluated every 4 weeks and retreated as needed through 52 weeks. those who did not achieve treatment success at week 8 continued hp/taz • participants were allowed 24 continuous weeks of hp/taz treatment if they achieved ≥1-grade improvement in iga from baseline at week 12, with monthly reevaluation for achievement of iga 0/1 • in this post hoc analysis, 550 participants were stratified by baseline severity of itch, dryness, and stinging/burning (none to mild vs moderate to severe) – itch and stinging/burning were scored on a scale from 0 (none) to 3 (severe) as reported by the participant in the past 24 hours – dryness was scored on a scale from 0 (none) to 3 (severe) as assessed by the investigator figure 1. design of the long-term open-label study of hp/taz. hp/taz, halobetasol propionate (0.01%) and tazarotene (0.045%) lotion; iga, investigator’s global assessment. atreatment success defined as iga score of clear (0) or almost clear (1) and ≥2-grade improvement from baseline iga. bimprovement defined as ≥1-grade improvement from baseline iga; those demonstrating improvement continued the study and were subsequently managed in 4-week cycles (ie, treated with once-daily hp/taz if they did not achieve treatment success or received no treatment until the next evaluation if they achieved treatment success). maximum continuous exposure was 24 weeks. results participant population • baseline characteristics are shown in table 1 table 1. participants stratified by baseline severity of signs/symptoms efficacy • at week 52, a greater proportion of participants with none-to-mild baseline signs/symptoms had treatment success (iga 0 or 1) compared with participants with moderate-to-severe baseline signs/symptoms (figure 2) figure 2. treatment success at week 52 among participants treated with hp/taz stratified by baseline severity of itch, dryness, and stinging/burning. hp/taz, halobetasol propionate (0.01%) and tazarotene (0.045%) lotion; iga, investigator’s global assessment. atreatment success defined as iga of clear (0) or almost clear (1). • participants with none-to-mild signs/symptoms at baseline were more likely to experience no signs/symptoms at any time point postbaseline relative to participants with moderate-to-severe signs/symptoms at baseline (figure 3) figure 3. participants without signs/symptoms at any time point postbaseline stratified by baseline severity of itch, dryness, and stinging/burning. • participants with moderate-to-severe itch (figure 4a), dryness (figure 4b), or burning/stinging (figure 4c) at baseline were more likely to experience moderateto-severe postbaseline local skin reactions figure 4. of the participants who experienced moderate-to-severe postbaseline signs/symptoms stratified by baseline severity of (a) itch, (b) dryness, and (c) burning/stinging. safety • rates of adverse events (aes) were similar across groups and discontinuations due to aes were low (range, 5.6%-8.3% across baseline subgroups), similar to what was seen in the overall population1 • application site dermatitis was the most common treatment-emergent ae across groups (table 2) table 2. treatment-emergent adverse events stratified by baseline severity of signs/symptoms long-term outcomes of fixed-combination halobetasol propionate and tazarotene lotion stratified by baseline signs and symptoms of psoriasis leon kircik,1 lawrence green,2 joshua zeichner,3 javier alonso,4 abby jacobson5 1icahn school of medicine at mount sinai, new york, ny; 2george washington university school of medicine, washington, dc; 3skin and laser center at mount sinai, new york, ny; 4coral gables dermatology & aesthetics, coral gables, fl; 5ortho dermatologics (a division of bausch health us, llc), bridgewater, nj acknowledgments: this study was sponsored by ortho dermatologics. medical writing support was provided by medthink scicom and funded by ortho dermatologics. ortho dermatologics is a division of bausch health us, llc. references: 1. lebwohl et al. j eur acad dermatol venereol. 2021;35:1152-1160. 2. elmets et al. j am acad dermatol. 2021;84:432-470. 3. duobrii [package insert]. bausch health us, llc; 2019. presented at the fall clinical dermatology conference • october 21-24, 2021 • las vegas, nv, and virtual sponsored by ortho dermatologics, a division of bausch health us, llc. participants, n (%) sign/symptom none to mild moderate to severe itch 278 (50.5) 272 (49.5) dryness 289 (52.5) 261 (47.5) stinging/burning 466 (84.7) 84 (15.3) participants, n (%) application site teae none-to-mild baseline itch moderateto-severe baseline itch none-to-mild baseline dryness moderate to-severe baseline dryness none-to mild baseline stinging/ burning moderate to-severe baseline stinging/ burning dermatitis 34 (12.2) 25 (9.2) 38 (13.1) 21 (8.0) 50 (10.7) 9 (10.7) pruritis 12 (4.3) 21 (7.7) 16 (5.5) 17 (6.5) 27 (5.8) 6 (7.1) pain 9 (3.2) 20 (7.4) 14 (4.8) 15 (5.7) 24 (5.2) 5 (6.0) irritation 8 (2.9) 6 (2.2) 10 (3.5) 4 (1.5) 13 (2.8) 1 (1.2) erosion 7 (2.5) 5 (1.8) 9 (3.1) 3 (1.1) 10 (2.1) 2 (2.4) erythema 4 (1.4) 4 (1.5) 6 (2.1) 2 (0.8) 7 (1.5) 1 (1.2) atrophy 0 4 (1.5) 1 (0.3) 3 (1.1) 2 (0.4) 2 (2.4) teae, treatment-emergent adverse event. 34.0 32.0 42.047.0 47.0 21.0 0 20 40 60 80 100 itch dryness stinging/burning pa rt ic ip an ts a ch ie vi ng tr ea tm en t su cc es s, % a baseline sign/symptom none to mild moderate to severe figure 2 17.6 17.6 40.3 4.4 4.2 7.1 0 20 40 60 80 100 itch dryness stinging/burning pa rt ic ip an ts w it ho ut po st ba se lin e si gn /s ym pt o m , % baseline sign/symptom none to mild moderate to severe figure 3 59.9 37.1 46.8 23.7 0 20 40 60 80 100 dryness stinging/burning participants with moderate-to-severe postbaseline sign/symptom, % po st ba se lin e si gn /s ym pt o m none-to-mild baseline itch moderate-to-severe baseline itch 72.4 31.8 57.4 29.1 0 20 40 60 80 100 itch stinging/burning participants with moderate-to-severe postbaseline sign/symptom, % po st ba se lin e si gn /s ym pt o m none-to-mild baseline dryness moderate-to-severe baseline dryness 83.3 77.4 61.2 48.9 0 20 40 60 80 100 itch dryness participants with moderate-to-severe postbaseline sign/symptom, % po st ba se lin e si gn /s ym pt o m none-to-mild baseline stinging/burning moderate-to-severe baseline stinging/burning a b c figure 1: study design week 52day 0 week 8 week 12 week 24 screening once-daily hp/taz for 8 weeks evaluated for treatment success at week 8a success treatment stopped for 4 weeks no success continued once-daily hp/taz for 4 weeks evaluated for improvement at week 12b continued study and managed in 4-week cycles for up to 1 year, with participants reevaluated every 4 weeks for treatment success • success: treatment stopped for 4 weeks • no success: continued once-daily hp/taz for 4 weeks no improvement discontinued from study if 24 weeks of continuous treatment were received at any point in the study and the participant did not achieve an iga score of 0 or 1, the participant was discontinued from the study. an adhesive patch biopsy based gene expression test to noninvasively differentiate basal cell �and squamous cell carcinomas from actinic keratoses and other skin lesions of similar appearance� introduction a data-driven evolution from subjective image recognition strategies to objective gene expression changes (that precede morphological changes) may contribute to a paradigm shift in how we practice dermatology and differentiate various skin conditions. a qrt-pcr-based non-invasive gene expression test that differentiates primary melanomas from similar looking benign pigmented lesions with high accuracy became available to dermatologists in the us recently.1-4 it may become a tool to improve patient care and contribute to such a development. demand by patients and clinicians for a similar test to non-invasively differentiate non-melanoma skin cancers (generally excised) from benign or precursor lesions (generally treated via non-surgical modalities such as cryotherapy or chemical and immunological destruction) has been growing. results with a robust qrt-pcr strategy utilizing a novel 13-target gene panel, we successfully differentiated bcc and scc cases from ak and other non-cancerous skin lesions of similar clinical appearance with a sensitivity of 91% (95% ci 86% 95%) and a specificity of 87% (95% ci 80% 92%) based on 160 non-invasively collected adhesive patch skin biopsies (p<0.001). an area under the curve (auc) value of 0.95 was observed (figure 1). conclusion the described approach of non-invasive gene expression testing differentiates primary cutaneous bcc and scc cases from benign and precursor lesions such as ak with high sensitivity and specificity. once fully validated in an ongoing large prospective study, such a test has the potential to reduce the number of avoidable surgical procedures while missing fewer cases of non-melanoma skin cancer. references study approach we initiated the development of such a qrt-pcr gene expression test based on targets identified through microarray screening of human transcriptomes from adhesive patch skin biopsy samples and literature searches. the identified target candidates were evaluated in prospectively collected basal (bcc) and squamous cell carcinoma (scc) as well as actinic keratosis (ak) and other control samples, also obtained via non-invasive adhesive patch biopsies. cycle threshold (ct) values from qrt-pcr analyses were used to demonstrate changes in target gene expression. algorithms were developed, trained and subjected to primary validation in 160 histopathologically confirmed cases. supported by dermtech, inc. gerami et al., development and validation of a non-invasive 2-gene molecular assay for cutaneous melanoma; jaad-d-16-00647r1, 2016. ferris et al., utility of a noninvasive 2-gene molecular assay for cutaneous melanoma and effect on the decision to biopsy. jama dermatology, 153(7)675-680, 2107. yao et al., analytical characteristics of a noninvasive gene expression assay for pigmented skin lesions. assay and drug development technologies, 14(6)355-363, 2016. yao et al., an adhesive patch-based skin biopsy device for molecular diagnostics and skin microbiome studies. journal of drugs in dermatology, 16(10)611-618, 2017. 1. 2. 3. 4. james e sligh 1, md, zuxu yao 2, phd, and burkhard jansen 2, southern arizona va healthcare system and university of arizona 1, tucson, az and dermtech inc 2, la jolla, ca 0.0 0.0 0.2 0.4 0.6 0.8 1.0 0.2 0.4 0.6 0.8 1.0 tr ue p os iti ve r at e (s en si tiv ity ) false positive rate (1 specificity) 0.95 (95% ci:0.92-0.97) auc figure 1. receiver operating characteristic curve demonstrating the bcc and scc samples from ak and other non cancer skin lesions. auc, area under the curve. fc17posterdermtechslighadhesivepatch.pdf methods • excised human abdominal skin samples of 500-µm thickness were pretreated with a 1440-nm laser with 80 microscopic treatment zones (mtz)/cm2 (1.2 w), 1440-nm laser with 320 mtz/cm2 (3 w), 1927-nm laser with 320 mtz/cm2 (1 w), or received no pretreatment (table 1) table 1. experimental parameters • following laser pretreatment, 10% ascorbic acid (obagi®, long beach, ca; 2010 formulation) was applied, and permeation was measured up to 24 hours after application (figure 1) • samples were filtered and analyzed using high-performance liquid chromatography to measure topical permeation and retention for laser-treated samples and untreated controls • total uptake was calculated as the sum of the normalized cumulative permeation and retention in each sample • average total uptake was compared between laser-treated samples and untreated controls to determine the uptake enhancement ratio figure 1. study design for testing uptake of topicals on skin tissue. pbs, phosphate-buffered saline. results permeation • pretreatment with the 1927-nm laser with 320 mtz/cm2 enhanced permeation of 10% ascorbic acid at 24 hours posttreatment relative to other pretreatments and untreated control (figure 2) figure 2. cumulative permeation of 10% ascorbic acid after laser pretreatment. values are mean ± standard deviation. mtz, microscopic treatment zones. uptake • pretreatment with the 1927-nm laser with 320 mtz/cm2 enhanced uptake by >4 times compared to the 1440-nm laser with 320 mtz/cm2 (7.8 vs 1.8 mg/cm2; table 2) – compared to the 1440-nm laser with 80 mtz/cm2 (0.5 mg/cm2), uptake was enhanced by >15 times – compared to untreated control (0.2 mg/cm2), uptake was enhanced by >33 times • pretreatment with the 1440-nm laser with 320 mtz/cm2 was associated with – >3-times greater uptake compared to the 1440-nm laser with 80 mtz/cm2 (1.8 vs 0.5 mg/cm2) – >7-times greater uptake compared to untreated control (1.8 vs 0.2 mg/cm2) table 2. uptake ratios of 10% ascorbic acid synopsis • the stratum corneum forms a vital protective barrier along the outer layer of the skin, but also prevents optimal uptake of topical formulations1 • lasers can facilitate better penetration and absorption of topicals by disrupting the stratum corneum and tight junctions in the epidermis2 • non-ablative lasers generally target dermal tissue and largely spare the stratum corneum, which minimizes overall thermal side effects and postprocedural recovery time, while fractionation further reduces postprocedural downtime3,4 • the relationship between topical uptake and laser device settings, such as wavelength, peak power, and spot density, must be quantified to optimize treatment benefits enhanced uptake of 10% ascorbic acid after 1440-nm or 1927-nm non-ablative fractional diode laser treatment jordan v. wang, md, mbe, mba1; paul m. friedman, md1,2; adarsh konda, pharmd3; catherine parker, np, msn4; roy g. geronemus, md1 1laser & skin surgery center of new york, new york, ny; 2dermatology and laser surgery center, houston, tx; 3bausch health us, llc, bridgewater, nj; 4solta medical, bothell, wa objective • to quantify uptake of 10% ascorbic acid following pretreatment with low-power 1440-nm or 1927-nm non-ablative fractional diode lasers (clear + brilliant® laser system; solta medical, bothell, wa) with varying treatment densities conclusions • in this ex vivo analysis, the greatest enhancement of 10% ascorbic acid uptake was seen with 1927-nm pretreatment at 320 mtz/cm2 and 1.0 w, compared to 1440-nm wavelengths at varying wattage and treatment densities • this provides a foundation for clinical studies on laser-enhanced uptake of ascorbic acid and other topicals, which can allow clinicians to better understand the relationship between quantifiable uptake enhancement and patientcentered outcomes presented at the 2021 fall clinical dermatology conference • october 21-24, 2021 • las vegas, nv, and virtual funding information: this study was sponsored by solta medical. medical writing support was provided by medthink scicom and funded by solta medical. disclosures: jvw is an investigator for solta medical. pmf serves on the advisory board and speaker bureau for solta medical. ak and cp are employees of and may hold stock or stock options in solta medical. rgg is an investigator and advisory board member for solta medical. references: 1. lee et al. eur j pharm sci. 2016;92:1-10. 2. machado et al. aesthetic plast surg. 2021;45:1020-1032. 3. friedman et al. j drugs dermatol. 2020;19:s3-s11. 4. farkas et al. aesthet surg j. 2013;33:1059-1064. figure 1 sample & refill 500-µm skin graft topical formulation pbs solution w/ 0.2% sodium azide donor chamber permeation/diffusion chamber stir bar stir rotation parameter setting device wavelength, nm 1440 1440 1927 spot density, mtz/cm2 80 320 320 peak power, w 1.2 3 1 spot size, µm 130 130 130 pulse energy, mj 9 9 9 mtz, microscopic treatment zones. 1440 nm (80 mtz/cm2) 1440 nm (320 mtz/cm2) 1927 nm (320 mtz/cm2) control 2.18 ± 0.55 x 7.75 ± 2.02 x 33.61 ± 0.02 x 1440 nm (80 mtz/cm2) — 3.56 ± 0.70 x 15.45 ± 0.02 x 1440 nm (320 mtz/cm2) — — 4.34 ± 0.07 x values are mean ± root mean square. mtz, microscopic treatment zones. -1 1 3 5 7 9 0 5 10 15 20 25 30 c um ul at iv e pe rm ea ti o n, m g/ cm 2 time, hours control kovar-1435nm tuscany-1435nm tuscany-1927nm control 1440 nm (80 mtz/cm2) 1440 nm (320 mtz/cm2) 1927 nm (320 mtz/cm2) 7.44 1.47 0.40 0.14 fcd.evidencereview.092818.4x4.submitted data from 3 studies and 2 physician surveys indicate that the 31-gep test results significantly impact management decisions for approximately 1 of 2 patients10-14 technical success studies demonstrate 99% interand 100% intra-assay concordance9, 15 evidence supports consistent ability of the 31-gep test to accurately identify recurrence, metastasis, and melanoma-specific mortality in cm patients1-8 sample adequacy literature review of a prognostic 31-gene expression profile (31-gep) test for cutaneous melanoma (cm) risk prediction robert w. cook, phd, kristen m. plasseraud, phd, sarah j. kurley, phd, kyle r. covington, phd, federico a. monzon, md, fcap castle biosciences, inc., friendswood, tx synopsis & objective in several cancers, molecular testing has added prognostic value and utility in the clinical setting. a 31-gene expression profile (31-gep) test has been developed and validated for determining metastatic risk in cutaneous melanoma, with class 1 and 2 results indicating low and high risks, respectively. as melanoma staging and guideline recommendations continue to evolve, it is important to consider the evidence supporting the use of clinicopathologic and molecular factors in melanoma patient care. herein, published evidence supporting the 31-gep test, including clinical validity, analytical validity, and clinical utility, are reviewed. from clinical validity evidence spanning eight peer-reviewed articles (n=1268 total patients) including two prospective studies, the 31-gep test consistently demonstrated accuracy to identify patients with cm at high risk for recurrence, metastasis, and melanoma-specific mortality. published analytical validity data verified the reliability of 31-gep testing with interand intraassay concordance of 99% and 100%, respectively, and 98% technical success on specimens with sufficient tumor content. clinical utility data from three studies (n=494 total patients) and two physician surveys indicate that the 31-gep test results significantly impact management decisions for approximately 1 of 2 patients, consistent with the impact of genomic testing in other cancers. in contrast to other prognostic melanoma gep tests that have been reported, the 31-gep test has published evidence from multiple retrospective and prospective clinical validity studies beyond initial development, along with published analytical validity and clinical utility data, in support of its use for melanoma risk assessment and patient management decisions. background & methods •the 31-gep test is performed in a capaccredited/clia-certified laboratory using high-throughput rt-pcr assays as previously described1-4. •clinical validity, analytical validity, and clinical utility studies surrounding the 31-gep are reviewed herein. this study was sponsored by castle biosciences, inc., which provided funding to contributing centers for tissue and clinical data retrieval. rwc, kpm, sjk, krc, & fam are employees and options holders of castle biosciences, inc. clinical validity clinical utility analytical validity references funding & disclosures conclusion case clinical features 1 0.6mm, 42y female, stage ia 2 0.54 mm, 62y male, stage ib, ulcerated, personal hx 3 0.76 mm, 69y male, stage ib, ulcerated, personal hx 4 >0.5mm, 45y male, stage ib/iia 5 0.9 mm, 61y female, stage ib, ulcerated, mitoses 6 1.2 mm, 38y female, stage iia, ulcerated does 31-gep testing alter management decisions and if so, for what modality?13 0 20 40 60 80 100 0.26 0.5 0.76 2.1 % r ec om m en di ng 3 1g e p breslow thickness (mm) percentage of dermatologists who would order the 31-gep test in different clinical scenarios baseline ulcerated sln negative * ** * ** **p<0.05 *p<0.001 adapted from svoboda et al. what features prompt physicians to recommend testing?14 adapted from farberg et al. *p<0.05 fisher’s exact test* * * figure 6. schematic representation of using ajcc staging with 31-gep test result to guide clinical management high risk class 2 consider increased surveillance intensity consider decreased intensity continue low intensity managementlow risk stage i-iia early detection of recurrence melanoma staging (per nccn) low risk class 1 high risk stage iib-iii high risk class 2 low risk class 1 continue high intensity management appropriate treatment or clinical trial ajcc staging 31-gep test management decision recommendation changes with gep result in patient vignettes technical reliability sufficient tumor content insufficient content (<40%) 96.3% n=16,472 98.3% n=16,190 3.7% n=630 1.7% n=282 successful gep multi-gene failure figure 8. the 31-gep test has high technical reliability on >17,000 clinical cases since july 201615 figure 7. 31-gep results are highly concordant between assays (n=168 cases)9 experiment 1 probability score e xp er im en t 2 p ro ba bi lit y s co re y = 0.9568x + 0.0115 r2 = 0.962 figure 2. the 31-gep test is an independent predictor of risk in a multivariate analysis across a large retrospective cohort of stage i-iii cases 4 1. gerami p, et al. clin cancer res 2015;21:175-83. 2. gerami p, et al. j am acad dermatol 2015;72:780-5 e783. 3. zager js, et al. bmc cancer 2018;18(1):130. 4. gastman br, et al. jaad 2018; doi: 10.1016/j.jaad.2018.07.028. 5. hsueh ec, et al. j hematol oncol 2017;10:152. 6. greenhaw b, et al. dermatol surg 2018; doi: 10.1097/dss.0000000000001588. 7. renzetti m, et al. society of surgical oncology annual meeting 2017. 8. hsueh ec, et al. j clin oncol 2016; 34(15_suppl):9565. 9. cook rw et al. diagn pathol 2018;13(1):13. 10. berger ac et al. curr res med opin 2016;32(9):1599-604. 11. dillon ld et al. skin: j cut med 2018;2(2):111-21. 12. schuitevoerder d et al. j drugs dermatol 2018;17(2):196-199. 13. farberg as et al. j drugs dermatol 2017;16(5):428-431. 14. svoboda rm et al. j drugs dermatol 2018;17(5):544. 15. berg as et al. derm2018 conference 2018 design (n) gep impact prospectively tested patients, retrospective chart review; (156 patients)10 53% prospective documentation of pre and post test plans; (247 patients)11 49% prospectively tested patients, retrospective chart review; (90 patients)12 52% physician survey of clinical decisions with or without test results; (169 physicians)13 4750% physician survey of clinical factors that affect use of 31-gep test; (181 physicians)14 * *overall gep impact not assessed with study design table 1. comparison of clinical utility studies figure 5. physician survey studies address key questions for 31-gep use13,14 cook et al. in review of the literature, the value of the 31-gep test for use in prognosis and clinical management decision making is supported by evidence from the 3 pillars of molecular tests: clinical validity, clinical utility, and analytical validity. cox multivariate analysis rfs dmfs mss hr 95% ci p-value hr 95% ci p-value hr 95% ci p-value breslow depth 1.21 1.121.3 <0.0001 1.19 1.091.29 <0.0001 1.16 1.01.34 0.05 mitotic rate 1.01 0.991.03 0.18 1.01 0.991.03 0.24 0.97 0.921.03 0.34 ulceration 1.1 0.751.59 0.64 1.57 1.022.43 0.04 0.77 0.381.57 0.47 positive node 2.45 1.743.46 <0.0001 3.02 2.04.57 <0.0001 3.83 1.857.95 0.0003 class 1b 1.13 0.562.29 0.73 1.35 0.583.15 .48 4.37 0.8422.72 0.08 class 2a 1.48 0.772.84 0.24 1.53 0.683.43 .30 2.52 0.4215.2 0.31 class 2b 2.92 1.75.00 <0.0001 2.89 1.495.62 0.002 9.02 2.0240.24 0.004 hr, hazard ratio; rfs, recurrence-free survival; dmfs, distant metastasis-free survival; mss, melanoma-specific survival; gep, gene expression profile; ci, confidence interval; 147 recurrences, 107 distant metastases, 36 melanoma-specific deaths subgroup analysis of this cohort also demonstrated independent ability of the 31-gep test to detect patients at high risk for metastasis in low-risk populations of sentinel lymph node-negative, stage i-iia, and t1 tumors. figure 1. accuracy metrics of the 31-gep test within a large retrospective cohort (n=690) •the 31-gep test predicts a cm patient’s risk of recurrence, metastasis, or melanomaspecific mortality at 5 years after diagnosis class 1 low risk of melanoma recurrence within 5 years class 2: high risk of melanoma recurrence within 5 years 1a lowest risk 2b highest risk 2a increased risk 1b low risk rna isolation cdna generation and amplification (14x) open array pcr gene card 28 discriminant gene targets and 3 control genes patients with stage i-iii melanoma primary cm tumor tissue formalin fixed, paraffin embedded (≥ 40% tumor content) analysis of gene expression profile with a proprietary algorithm to determine class and metastatic risk change studyberger et al. dillon et al. class 1 changed 37% 36% changed class 1 w/ decrease 94% 67% class 2 changed 77% 85% changed class 2 w/ increase 94% 92% figure 4. 31-gep result drives surveillance changes in multicenter studies10,11 consistent specific modality changes across both studies: • decreases in imaging, visits, and referrals with class 1 result • increases in labs, imaging, visits and referrals with class 2 result multi-center study5 n=322% r ec ur re nc e fr ee figure 3. 31-gep class divides patients into high and low-risk categories for recurrence, metastasis and death across multiple prospective studies5,6,8 class 1 class 2 p<0.0001 single-center study6 p<0.0001 time (years) p ro ba bi lit y a vo id in g m et as ta tic d is ea se % m et as ta si s fr ee hsueh et al. asco 2016 time (months) n=159 p<0.00001s u rv iv a l p ro b a b il it y 1.0 0.8 0.6 0.4 0.2 0 additional single-center study8 class 1 class 2 p<0.00001 % s ur vi va l -30 -20 -10 0 10 20 30 40 50 60 1 2 3 4 5 6 class 1 class 2 % o f p hy si ci an s re co m m en di ng (c om pa re d to w ith ou tg e p re su lt) imaging slnb -30 -20 -10 0 10 20 30 40 50 60 1 2 3 4 5 6 * * * * * * * * * * * * * * * * * * * powerpoint presentation winter clinical miami • feb 17 – 20th, 2023 • moderate-to-severe atopic dermatitis (ad) has a significant negative impact on quality of life in adults and adolescents1,2 • despite being eligible for advanced systemic therapy (ast) due to uncontrolled moderate or severe ad, many adolescent patients do not progress to ast • this study characterizes the population of adolescent (age 12-17) patients with moderate-to-severe ad who were ast-treated to those who were not ast-treated (ast-naïve) to better understand progression to ast-usage in these patients. results ast-usage • less than 50% of patients were treated with an ast among the 91 adolescents who met study criteria: 55% (n=50) were ast-naïve, and 45% (n=41) were ast-treated • all ast treatment was with dupilumab, no upadacitinib usage reported • of 44 physicians, 36 (82%) were dermatologists and 8 (18%) allergists in this analysis. all 41 ast-treated patients (100%) saw a dermatologist, and none saw allergist (0%), of the ast-naïve 42 (84%) saw a dermatologist and 8 (16%) an allergist (p=0.008) ast-naïve vs. ast-treated descriptive analysis • no significant differences were observed between ast-usage groups for age, gender, race, insurance type, treatment center, viga-ad, cdlqi, poem, promis depression, promis anxiety, or prior use of topical therapies at enrollment • ast-treated had significantly higher median enrollment severity on two measures of disease severity • bsa (35% vs 15%, p=0.0076) • viga-ad x bsa (105 vs 48, p<0.0066) • ast-treated had a significantly higher po-scorad at enrollment vs ast-naïve (45.8 vs. 31.1, p<0.03) ast-naïve vs ast-treated multivariate analysis • in multivariate analysis controlling for sex, age, insurance, and race, only higher bsa at enrollment was associated with ast-usage • bsa of 5% or=1.09 (1.01-1.19) • bsa of 10% or = 1.2 (1.01-1.42) • bsa of 20% or = 1.43 (1.02-2.01) 1 rady children’s hospital, san diego, ca 2 university of california san diego, san diego, ca 3 target rwe, durham, nc 4 leo pharma inc., madison, nj 5 george washington school of medicine, washington dc 6 university of lübeck, lübeck germany use of advanced systemic therapy in adolescent patients with moderate-to-severe atopic dermatitis in the target-derm registry haft m1,2, knapp k3, claxton a4, hernandez b3, balu s4, schneider s4, silverberg j5, thaci d6, eichenfield l1,2 on behalf of target-derm investigators conclusion • more than half of the patients with considerable disease severity and who experienced negative qol from moderate-to-severe ad were not prescribed ast • compared to ast-naïve patients, descriptive analysis showed that the asttreated were slightly more severe as indicated by significantly higher baseline bsa, higher viga-adxbsa, and higher po-scorad at enrollment. • in multivariate analysis to adjust for baseline characteristics, higher bsa at enrollment was significantly associated with use of an ast. • longitudinal follow-up is needed to determine the outcomes associated with these treatment patterns to evolve therapeutic interventions and outcomes in these adolescent patients. variables of interest: • patient demographics • site and physician type • prior and concomitant topical ad therapy (any, calcineurin inhibitor, corticosteroid, phosphodiesterase) disease severity measures: • viga-ad (scores 0-4) • total body surface area (bsa) (score 0-100%) • viga-ad x bsa (score 0-400) patient population: • adolescent (12-17 years) • moderate or severe ad defined as a score of 3 or 4 on the validated investigator global assessment ad (viga-ad) at enrollment • treatment history: had prior exposure to at least one of the following: topical corticosteroid, systemic corticosteroid, immunomodulator or phototherapy • had at least 1 post-enrollment visit • excluded were clinical trial patients and any patient treated with an ast prior to enrollment methods target-derm ad all patients n=2549 age 12-17 (n=327) met treatment history criteria (n=186) study population n=91 • ast-naïve (n=50) • ast-treated (n=41) ast-treated n=41 • moderate n=23 • severe n=18 ast-naïve n=50 • moderate n=37 • severe n=13 excluded: ast users prior to enrollment (n=34) and clinical trial patients (n=0) had 1+ follow-up visits (n=125) moderate or severe ad: viga-ad of 3 or 4 (n=191) figure 1. patient disposition acknowledgements and disclosures target rwe communities are collaborations among academic & community investigators, the pharmaceutical industry, and patient community advocates. target rwe communities are sponsored by target pharmasolutions inc (d.b.a., target rwe). the authors would like to thank all the investigators, participants, and research staff associated with target-derm ad. clinicaltrials.gov identifier: nct03661866. leo pharma is a target rwe industry partner which subscribes for data access. mh has no financial disclosures. kk and bh are employees of target rwe. ac, sb, and ss are employees of leo pharma. js received honoraria as a consultant and/or advisory board member for abbvie, afyx, aobiome, arena, asana, aslan, biomx, biosion, bluefin, bodewell, boehringer-ingelheim, cara, castle biosciences, celgene, connect biopharma, dermavant, dermira, dermtech, eli lilly, galderma, glaxosmithkline, incyte, kiniksa, leo pharma, luna, menlo, novartis, optum, pfizer, rapt, regeneron, sanofi-genzyme, shaperon, sidekick health, union; speaker for abbvie, eli lilly, leo pharma, pfizer, regeneron, sanofi-genzyme; institution received grants from galderma, pfizer; dt abbvie, almirall, amgen, biogen idec, boehringer ingelheim, dermira, eli lilly, galderma, gsk, janssen-cilag, leo-pharma, novartis, pfizer, regeneron, roche, sandoz-hexal, sanofi, and ucb; consultant: abbvie, almirall, amgen, dignity, galapagos, leo pharma, maruho, mitsubishi, novartis, sanofi, pfizer, regeneron, target-solution, and ucb; lectures: abbvie, almirall, amgen, janssen, leo pharma, msd, novartis, pfizer, roche-posay, sandoz-hexal, sanofi, and ucb; scientific advisory board: abbvie, boehringer ingelheim, eli lilly, galapagos, janssen-cilag, leo pharma, morphosis, novartis, pfizer, regeneron, sanofi, and ucb; le has served as a scientific adviser, consultant, and/or clinical study investigator for abbvie, almirall, arcutis, arena, aslan, dermavant, eli lilly, forté, galderma, incyte, janssen, leo pharma, novartis, ortho, otsuka, pfizer, regeneron, sanofi genzyme fig 2a. patient characteristics by ast-usage patient reported outcomes: • cdlqi: children’s dermatology life quality index (scores 0-30) • poem: patient-oriented eczema measure (scores 0-28) • po-scorad: patient-oriented scoring atopic dermatitis (scores 0-103) • patient-reported outcomes measurement information system (promis) depression (scores 41.0-79.4) and promis anxiety (scores 40.9-85.2) references 1. nutten, s., atopic dermatitis: global epidemiology and risk factors. ann nutr metab, 2015. 66 suppl 1: p. 8-16. 2. ad langan sm, irvine ad, weidinger s. lancet. 2020 aug 1;396(10247):345-360. 3. abuabara, k. international observational atopic dermatitis cohort to follow natural history and treatment course: targetderm ad study design and rational bmj open 2020;10:e0399282020. figure 3. factors associated with ast-treatment. significant values are in blue. • target-derm ad is an ongoing, longitudinal, observational study of adult and adolescent dermatology patients managed in clinical practice at 32 community (n=15) or academic (n=17) sites in the united states; first patients were enrolled in jan. 25th, 2019. 3 the data cutoff for this analysis was aug 11, 2022. • ast is defined as dupilumab (adolescent indication approved 05/262020) and upadacitinib (adolescent indication approved 01/11/22) • , approved treatments for adolescents with moderate-to-severe ad. • patients were classified into two unique ast usage groups: ast-treated (any ast usage at or after enrollment) or ast-naïve (no ast usage at or after enrollment). • data was analyzed descriptively. the association between clinical/pros and astusage was estimated by multivariate binary logistic regression controlling for age, race, gender, insurance, and site type. • all analysis was conducted on enrollment (baseline) data introduction figure 2b. median clinical and pro scores by ast-usage 0 20 40 60 80 100 120 b s a ( % ) v ig a -a d x b s a p o -s c o r a d p o e m p r o m is d e p re ss io n (t -s co re ) p r o m is a n xi e ty (t -s co re ) m e d ia n s co re ast-naïve ast-treated 0.0% 10.0% 20.0% 30.0% 40.0% 50.0% 60.0% 70.0% 80.0% 90.0% 100.0% f e m a le ( % ) h is p a n ic /l a ti n o n h w h it e n h b la ck a si a n o th e r/ n o t re p o rt e d m o d e ra te s e ve re a n y p ri o r to p ic a l tr e a tm e n t p ri o r ca lc in e u ri n i n h ib it o r tr e a tm e n t p ri o r co rt ic o st e ro id tr e a tm e n t p ri o r p h o sp h o d ie st e ra se in h ib it o r tr e a tm e n t a ll e rg is t d e rm a to lo g is t m e d ic a id p ri va te u n in su re d a ca d e m ic c o m m u n it y sex race/ethnicity viga topical medication treatment specialty insurance site type p e rc e n ta g e ast-naïve ast-treated in addition to the covariates listed above, other factors were considered, but were not found to be significant; data not shown or (95% ci) 0.98 (0.4 – 2.43) 1.17 (0.44 – 3.11) 0.88 (0.37 – 2.12) 0.68 (0.27 – 1.75) 1.17 (0.46 – 2.98) 1.09 (1.01 – 1.19) 1.2 (1.01 – 1.42) 1.43 (1.02 – 2.01) age: 15-17 vs. 12-14 race: non nh-white vs nh-white sex: male vs. female insurance: non-private vs private site type: academic vs community increase in 5% of bsa increase in 10% of bsa increase in 20% of bsa p=0.0076 p=0.0066 p=0.0241 __p=0.008__ slide 1 acknowledgements study and poster funded by galderma laboratories, l.p., fort worth, txgalderma would like to thank drs. swinyer, browning, hull, t schlesinger, mandy, cook-bolden, grekin, green, draelos, werschler, j schlesinger, and thiboutot for their participation in this study. introduction • acne vulgaris (av) is the 8th most prevalent disease worldwide av affects an estimated 85% of individuals between 12 and 24 years of age1,2 • prompt and effective treatment is needed to prevent long term consequences, such as scarring • oral isotretinoin (oi) is considered an effective treatment for many severe av patients; however, oi has known and serious side effects treatment cannot always be initiated immediately · isotretinoin is a potent teratogen, and exposure should be avoided by women who are or may become pregnant • current acne treatment guidelines for first-line treatment of severe acne suggest using oi or a topical therapy combined with oral antibiotics3 adapalene 0.3%/benzoyl peroxide 2.5% (a/bpo 0.3%/2.5%) gel is approved for the treatment of av · a/bpo 0.3%/2.5% gel attacks 3 of the 4 major pathogenic factors of av · a/bpo 0.3%/2.5% gel has strong clinical efficacy and excellent safety and tolerability in subjects with moderate to severe av4 efficacy and safety of adapalene 0.3% / benzoyl peroxide 2.5% gel plus doxycycline in subjects with severe inflammatory acne (non-nodulocystic) that are candidates for oral isotretinoin james del rosso, do1; linda stein gold, md2; sandra marchese johnson, md, faad3; maria jose rueda, md4; hilary baldwin, md5; edward l. lain, md6; megan landis, md7; marta rendon, md8; emil tanghetti, md9, jonathan weiss, md11 1jdr dermatology research/thomas dermatology, las vegas, nv; 2henry ford medical center, dept. of dermatology, detroit, mi; 3johnson dermatology, fort smith, ar; 4galderma laboratories, l.p., fort worth, tx; 5the acne treatment and research center, morristown, nj; 6austin institute for clinical research, pflugerville, tx; 7dermatology specialists research, new albany, in; 8rendon center for dermatology and aesthetic medicine, boca raton, fl; 9center for dermatology and laser surgery, sacramento, ca, 11gwinnett dermatology, snellville, ga epi.p-ma10355-07 summary ■ this study observed that 12 weeks of a/bpo 0.3%/2.5% gel plus dox 200 mg was an effective, safe, and well tolerated therapy for subjects with severe av (non-nodulocystic, non-conglobate) mean lesion count reduction and mean percent reduction in lesions were significant compared with baseline (p < .0001 vs baseline, all study visits) 37.1% of subjects received an iga of clear or almost clear (iga success) at week 12 most subjects (80.1%) were no longer assessed as candidates for oi by the investigators after 12-weeks of a/bpo 0.3%/2.5% gel plus dox 200 mg treatment ■ twelve weeks of a/bpo 0.3%/2.5% gel plus dox 200 mg is an effective and safe regimen for subjects with severe av (non-nodulocystic, non-conglobate) who are also candidates for oi for subjects who must wait before starting oral isotretinoin as an alternative option for those unwilling to use oral isotretinoin for those unable to use oral isotretinoin due to contraindications subjects and methods • open label, single arm, 12-week, multicenter study of a/bpo 0.3%/2.5% gel+dox† 200 mg • twenty-three sites enrolled males and females, 12 years of age or older, with a clinical diagnosis of severe inflammatory acne (investigator's global assessment [iga] score = 4) who had never received oi, and, in the opinion of the investigator, were candidates for oi subjects had ≤ 4 nodules/cysts > 1 cm in diameter on the face · subjects were excluded if they had nodulocystic or conglobate acne, acne fulminans, or secondary acne (eg, chloracne, drug-induced acne) • treatments: topical a/bpo 0.3%/2.5% gel, once daily for 12 weeks dox 200 mg (2x 50 mg tablets, mayne, doryx), twice daily (morning and evening) for 12 weeks cetaphil® gentle cleanser* (or equivalent), twice daily cetaphil® daily facial moisturizer spf 15* (or equivalent), at least once daily and re-apply as needed • endpoints and assessments: reduction and percent reduction in lesions at weeks 4, 8, and 12 iga (iga, 0 – 4 scale): success (subjects rated iga 0 or 1) at weeks 0, 4, 8, and 12 number and percent of subjects who, in the opinion of the investigator, are candidates for oral isotretinoin at weeks 0, 4, 8, and 12 · investigator evaluation of each subject’s candidacy to oi was performed independently at each visit, without consideration of previous visits photographs were taken of all subjects enrolled in the study at all study visits incidence of adverse events (aes) and local tolerability (0 [none] – 3 [severe] scale) *cetaphil® gentle cleanser and cetaphil® daily facial moisturizer spf 15 are manufactured by galderma laboratories, l.p. †dox = doxycycline 200 mg (2x 50 mg tablets, mayne, doryx) *p < .0001 100 0 20 80 40 60 pe rce nt o f s ub je cts baseline week 4 week 8 week 12 0.5% n = 1 3.8% n = 7 4.8% n = 9 23.1% n = 43 33.3% n = 62 32.3% n = 60 40.3% n = 75 38.7% n = 72 37.1% n = 69 20.4% n = 38 12.9% n = 24 100.0% n = 186 25.8% n = 48 15.6% n = 29 11.3% n = 21 41.9% n = 78 65.1% n = 121 80.1% n = 149 100.0% n = 186 58.1% n = 108 34.9% n = 65 19.9% n = 37 oi iga oi iga oi iga oi iga iga 0: clear iga 1: almost clear iga 2: mild iga 3: moderate iga 4: severe oi candidate * * * success = 0 (0) success* = 9 (4.8%) success* = 44 (23.7%) success* = 69 (37.1%) figure 1. investigator assessed oi candidacy and iga by study visit (itt, locf, n = 186) references 1. tan jk, bhate k. a global perspective on the epidemiology of acne. br j dermatol. jul 2015;172 suppl 1:3-12. 2. landis et, davis sa, taheri a, feldman sr. top dermatologic diagnoses by age. dermatol online j. 2014;20(4):22368. 3. gollnick hp, bettoli v, lambert j, et al. a consensus-based practical and daily guide for the treatment of acne patients. j eur acad dermatol venereol. sep 2016;30(9):1480-1490. 4. stein gold l, weiss j, rueda mj, liu h, tanghetti e. moderate and severe inflammatory acne vulgaris effectively treated with single-agent therapy by a new fixed-dose combination adapalene 0.3 %/benzoyl peroxide 2.5 % gel: a randomized, double-blind, parallel-group, controlled study. am j clin dermatol. jun 2016;17(3):293-303. figure 5. representative subject photographs subject 147-003: 18 year old male subject 108-026: 19 year old female subject 108-028, 14 year old male i/n 61/64, iga 4, y i/n 60/120, iga 4, yi/n 41/22, iga 4, y i/n 3/8, iga 1, n i/n 16/26, iga 3, yi/n 6/33, iga 1, n baseline baseline baselineweek 12 week 12week 12 i/n = inflammatory/ noninflammatory lesions y = investigator opinion: this subject is a candidate for oral isotretinoin n = investigator opinion: this subject is not a candidate for oral isotretinoin results • the study enrolled 186 subjects 175 subjects received at least one dose of the study treatment male (n = 78) and female (n = 97) mean age = 19.6 ± 7.3 (56% ≤ 17 years of age) most subjects were white (79%) and not hispanic or latino (81%) baseline lesion counts; mean (sd) · inflammatory = 44.8 (21.7); non-inflammatory = 65.3 (39.4); total = 110.1 (49.4) • subjects who were not considered candidates for oi by the investigator (figure 1) 41.9% after 4 weeks; 65.1% after 8 weeks; 80.1% (149/186) after 12 weeks • 75.8% of subjects were rated iga 2 (mild) or better by week 12 (figure 1) • iga success rate (clear and almost clear; figure 1) 4.8% at week 4; 23.7% at week 8; 37.1% at week 12 • mean number of lesions: significantly reduced compared with baseline (p < .0001 vs baseline, all study visits; figure 2) at week 12 the total mean reduction in lesions was -26.2 lesions compared with baseline (p < .0001) • percent lesion reduction: significant reduction compared with baseline (p < .0001 vs baseline, all study visits; figure 3) at week 12 the total mean percent reduction in lesions was -62.6% compared with baseline (p < .0001) • safety a/bpo 0.3% was well tolerated and most aes were mild (figure 4) the number of subjects experiencing any treatment emergent ae was 46 (26.3%) the number of subjects with any treatment related ae was 27 (15.4%) the most common treatment related aes were skin burning sensation (n = 6, [3.4%]) and erythema (n = 5, [2.9%]) 120 20 60 100 40 80 0 m ea n le sio n co un t baseline week 4 week 8 week 12 44.8 26.0 19.0 14.8 65.3 40.4 31.7 26.2 110.1 66.3 50.6 40.9 inflammatory non-inflammatory total † † †† † † † † † figure 2. lesion counts (itt, locf, n = 185*) *baseline lesion counts missing for 1 patient (itt, n = 186); †p < .0001 vs baseline, at all post-baseline assessments -50 -20 -60 -10 -40 -30 -70 0 m ea n pe rce nt c ha ng e baseline week 4 week 8 week 12 inflammatory non-inflammatory total -38.5 -55.0 -66.2 -34.6 -50.2 -58.7 -38.9 -53.9 -62.6 † † † † † † † † † figure 3. percent reduction in lesion count (itt, locf, n = 185*) *baseline lesion counts missing for 1 patient (itt, n = 186); †p < .0001 vs baseline, at all post-baseline assessments m ea n to le ra bi lit y s co re baseline week 4 week 8 week 12 n = 175 severity scale: 0 = none, 1 = mild, 2 = moderate, 3 = severe n = 166 n = 161 n = 165 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 1 = mild erythema scaling dryness stinging/burning 13 (7.8) 0 (0) 4 (2.5) 0 (0) 7 (4.2) 1 (0.6) 0 (0) 4 (2.5) 0 (0) 2 (1.2) 3 (1.8) 0 (0) 1 (0.6) 0 (0) 2 (1.2) 1 (0.6) 12(7.2) 1 (0.6) 1 (0.6) 1 (0.6) 2 (1.2) 18 (10.3) 2 (1.1) 1 (0.6) 1 (0.6) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 2 (1.2) number and percent of subjects with tolerabiliity scores of moderate/severe at each time point, n (%) figure 4. local tolerability (safety population) note: tolerability data was only collected at study visits (no tolerability data was collected for weeks 1 through 3). fc17postergaldermadelrossoefficacysafetygel.pdf skin july 2021 1265 proof returned skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 437 brief article a subacute cutaneous lupus erythematosus-like drug eruption related to terbinafine in a male haley d. heibel, md1, sidra ibad, ba2, parneet dhaliwal, do3, sharif currimbhoy, md4, clay j. cockerell, md, mba1,5 1 cockerell dermatopathology, dallas, tx 2 icahn school of medicine at mount sinai, new york, ny 3 department of pathology, baylor university medical center, dallas, tx 4 denton dermatology, denton, tx 5 departments of dermatology and pathology, ut southwestern medical center, dallas, tx terbinafine is an oral allylamine antifungicidal medication that is commonly used to treat dermatophyte infections of the skin and nails.1-3 although terbinafine is generally well-tolerated, side effects occur in approximately 2-10% of patients.1,2 these include cutaneous reactions of urticaria, pruritus, exanthems, papulopustular eruptions, hyperpigmentation, erythema multiforme, toxic epidermal necrolysis, acute generalized exanthematous pustulosis, pustular psoriasis, psoriasis flare, and druginduced subacute cutaneous lupus erythematosus (scle).1,4,5 here, we report a case of terbinafine-induced scle in a male patient. however, classic scle most commonly affects females, and he did not have a diagnosis of or a history suggestive of a predisposition to autoimmune or collagen vascular diseases.3 an 85-year-old male presented to the dermatologist with nonpruritic and nontender red plaques on his trunk and bilateral arms and legs that had been present for 3 weeks. he had initiated terbinafine for onychomycosis approximately 7 and a half weeks prior to presentation and then discontinued after one month of treatment. he denied fevers, chills, cough, and shortness of breath. physical examination demonstrated scattered pink to red polycyclic abstract although terbinafine is generally well-tolerated, side effects occur in approximately 2-10% of patients. patients with a history of or a predisposition to autoimmune or collagen vascular diseases may be inclined to develop drug-induced subacute cutaneous lupus erythematosus (scle) due to terbinafine therapy. here, we report a case of terbinafine-induced scle in a male patient. however, classic scle most commonly affects females, and he did not have a diagnosis of or a history suggestive of a predisposition to autoimmune or collagen vascular diseases. although the mechanism for terbinafineinduced scle has not been fully elucidated, we suggest that there may be distinctive mechanisms of terbinafine-induced scle of patients with and without a predisposition to or history of autoimmune or connective tissue diseases, which should be a focus for future research. introduction case report skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 438 annular plaques on his trunk and bilateral arms and lower legs (fig. 1), some with overlying scale and with heme crust, but there was no ocular or oral mucosal involvement. figure 1.terbinafine-induced subacute cutaneous lupus erythematosus. scattered pink to red polycyclic annular plaques, some with overlying scale and with heme crust, on the bilateral arms and trunk. there were also lesions on the bilateral lower legs. histopathologic examination of a biopsy from the right upper arm demonstrated an interface dermatitis as well as a superficial and mid-dermal perivascular infiltrate of lymphocytes and dermal mucin and overlying parakeratosis (figs. 2a-b). laboratory data was significant for mild normocytic anemia, and complete metabolic panel was significant for mildly elevated creatinine (1.53 mg/dl) consistent with his baseline creatinine, but was otherwise unremarkable. erythrocyte sedimentation rate was elevated, and ige level was normal. at his follow-up visit 9 days later, he demonstrated clinical improvement with the application of triamcinolone cream 0.1% to affected areas of the body twice daily and avoidance of terbinafine. however, he continued to develop additional lesions on the legs. at this time, betamethasone dipropionate cream 0.05% was prescribed to apply once daily to darker red and pink lesions with the continuation of triamcinolone cream to lighter pink lesions. he has continued to improve clinically with resolution of most lesions and diminished erythema upon follow-up approximately 3 weeks after the initiation of therapy. no further serologic studies for lupus erythematosus were completed, as there was low clinical suspicion due to the patient’s age of onset of the eruption and clinical improvement with the cessation of terbinafine therapy. patients with a history of, or a predisposition to, autoimmune or collagen vascular diseases are inclined to develop druginduced scle due to terbinafine therapy.6,7 there have been reports of patients with systemic lupus erythematosus (sle) who developed scle after terbinafine therapy.4,6 although an exacerbation of sle is not commonly observed in the setting of terbinafine-induced scle, one case described a terbinafine-induced flare in a patient with bullous lupus erythematosus.5,6 in addition, one case of scle that developed during terbinafine therapy for onychomycosis was associated with chilblain lupus.1 there have also been reports of patients with symptoms and signs of autoimmune dysfunction who developed scle with terbinafine therapy.2,7 terbinafine-induced scle has been associated with high titers of antinuclear antibodies (ana) and the presence of anti-ro (ss-a) antibodies, anti-la (ss-b) antibodies, and anti-histone antibodies, although the presence of anti-histone antibodies is less common.1,3,6 discussion skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 439 bonsmann et al1 observed that ana titers and anti-histone antibodies decreased with figure 2. histology of terbinafine-induced subacute cutaneous lupus erythematosus at a) low power h & e, 40x and b) high power h &e, 100x. biopsy of the right upper arm demonstrated an interface dermatitis as well as a superficial and mid-dermal perivascular infiltrate of lymphocytes and dermal mucin and overlying parakeratosis. the discontinuation of terbinafine that coincided with the resolution of the scle eruption in all 4 patients with terbinafineinduced scle. the mechanism of terbinafine causing scle in predisposed patients (such as a history of systemic lupus erythematosus or scle, positive antinuclear antibodies, and/or presence of photosensitivity, raynaud’s phenomenon, arthralgia, myalgia, and dryness of the mucous membranes) has not been fully elucidated, but it may involve the alteration of terbinafine or its metabolites by ultraviolet radiation.1,7 additionally, due to the lipophilic and keratophilic nature of terbinafine, autoantibody development may occur in susceptible persons due to the deposition of terbinafine in keratinocytes and modification of the nuclear antigen structure.1 terbinafine may also augment the antibodydependent, cell-mediated cytotoxic reaction in which anti-ro autoantibodies cause keratinocyte damage.1 in these predisposed patients, there should be special consideration about the potential for terbinafine to induce or exacerbate the disease process.4,7 however, it is possible that there may be a different mechanism for the development of terbinafine-induced scle in patients who do not have a history suggestive of a predisposition to or diagnosis of autoimmune or collagen vascular diseases, as in our patient although there were no serologic studies done in this case, it would be interesting to note if this patient demonstrated positive screens for autoimmune disease prior to and subsequent to the administration of terbinafine, and to further study the distinctive mechanisms of terbinafine-induced scle of patients with and without a predisposition to or history of autoimmune or connective tissue diseases. conclusion a b skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 440 conflict of interest disclosures: none funding: none corresponding author: haley d. heibel, md 2110 research row suite 100 dallas, tx 75235 phone: 214-530-5200 fax: (877) 561-0039 email: hheibel@dermpath.com references: 1. bonsmann g, schiller m, luger ta, ständer s. terbinafine-induced subacute cutaneous lupus erythematosus. j am acad dermatol 2001;44(6):925-931. 2. hivnor cm, hudkins ml, bonner b. terbinafineinduced subacute cutaneous lupus erythematosus. cutis 2008;81(2):156-157. 3. mckay da, schofield om, benton ec. terbinafine-induced subacute cutaneous lupus erythematosus. acta derm venereol 2004;84(6):472-474. 4. cetkovská p, pizinger k. coexisting subacute and systemic lupus erythematosus after terbinafine administration: successful treatment with mycophenolate mofetil. int j dermatol 2006;45(3):320-322. 5. tappel ac, tiwari n, saavedra a. terbinafineinduced relapse of bullous lupus erythematosus. j clin rheumatol 2018. 6. kalińska-bienias a, kowalewski c, woźniak k. terbinafine-induced subacute cutaneous lupus erythematosus in two patients with systemic lupus erythematosus successfully treated with topical corticosteroids. postepy dermatol alergo 2013;30(4):261-264. 7. kasperkiewicz m, anemüller w, angelovafischer i, rose c, zillikens d, fischer tw. subacute cutaneous lupus erythematosus associated with terbinafine. clin exp dermatol 2009;34(7):e403-e404. background • acne vulgaris (av) is a common skin disease that affects adolescents and can persist into adulthood1 • the mainstay of treatment for av is systemic tetracyclines, such as doxycycline and minocycline2 • fmx101 4% is a novel topical foam formulation of minocycline. it has been shown to be an effective and well-tolerated treatment for moderate-to-severe av in a phase 2 clinical trial3 • two phase 1 studies were conducted to characterize minocycline pharmacokinetics (pk) and safety following multiple-dose administration of fmx101 4% minocycline foam in adult (study fx2014-03) and pediatric (study fx2016-21) patients with moderate-to-severe av methods • 2 phase 1, single-center, nonrandomized, open-label studies (figure 1, table 1) • adults (age 18 to 35 years) or pediatric subjects (age 9 years to 16 years, 11 months) with moderate-to-severe av – adult study (fx2014-03) first received a single 1-mg/kg oral dose of oral extendedrelease minocycline hcl tablet (solodyn®). then, after 10 days, they received a once-daily topical application of 4 g fmx101 4% to the face, neck, upper chest, upper back, shoulders, and upper arms for 21 days – pediatric study (fx2016-21) received once-daily topical application of 4 g fmx101 4% to the face, neck, upper chest, upper back, shoulders, and upper arms for 7 days figure 1. study design table 1. inclusion criteria and assessments adult study (fx2014-03) pediatric study (fx2016-21) inclusion criteria • healthy males/females aged 18–35 years • moderate-to-severe facial av (additionally affecting ≥2 regions of neck, upper chest, upper back, or arms) • bmi within 18.5-29.9 kg/m2 ; body weight within 48.0-128.0 kg • not pregnant, lactating, or planning a pregnancy during study • healthy males/females aged 9 years to 16 years, 11 months – subjects <12 years: mild facial acne and acne of limited extent – subjects 12–16 years: moderate-to-severe av based on 5-point iga scale and acne affecting ≥1 of the following: neck, upper chest, upper back, or arms • sexually inactive, sterile, or using contraception blood sampling for drug concentration • predose through 96 hours after administration of oral minocycline • predose through 24 hours after fmx101 4% application on days 1, 12, and 21 • prior to scheduled application on days 6, 9, 10, 11, and 16 • on and after day 21, at 24 hours (day 22), 48 hours (day 23), 72 hours (day 24), and 96 hours (day 25) from last application of fmx101 4% • on day 7, after 3, 12, 16, and 24 hours from last application of fmx101 4% pharmacokinetic analyses • pk parameters were calculated using noncompartmental methods • pk parameters included auc0-inf, auc0-tau, auc0-tldc, cmax, c24, tmax, t1/2, and accumulation ratio • pk parameters were calculated using noncompartmental methods • pk parameters included auc0-tau, cmax, and c24 statistical analyses • geometric mean was calculated for auc0-inf, auc0-tau, auc0-tldc, and cmax • geometric mean was calculated for auc0-tau and cmax auc 0-inf =auc from 0 to infinity. auc 0-tau =auc during the 24-hour dosing interval. auc 0-tldc =auc from 0 to time of last determinable concentration. c 24 =plasma minocycline concentration 24 hours after fmx101 4% application. c max =maximum plasma drug concentration. t 1/2 =terminal phase half-life. t max =time of maximum measured plasma drug concentration. bmi=body mass index. iga=investigator’s global assessment. results baseline demographics • baseline characteristics are shown in table 2 • all adult subjects had moderate-to-severe av • a majority of pediatric subjects (90%) had moderate av, and 1 subject had mild av table 2. baseline characteristics adult study (fx2014-03) (n=30) pediatric study (fx2016-21) (n=20) mean age (range), yr 22.6 (18-30) 13.2 (10-16) gender, n (%) male/female 12 (40) / 18 (60) 9 (45) / 11 (55) race, n (%) white black or african american 27 (90) 3 (10) 7 (35) 13 (65) ethnicity, n (%) hispanic/latino non-hispanic/latino 11 (36.7) 19 (63.3) 2 (10) 18 (90) pharmacokinetics – adults • the mean plasma concentration of oral minocycline in adult subjects reached c max by 3 hours after administration, followed by a log-linear decrease in concentration for the remaining 96-hour sample period • the mean plasma minocycline concentration of fmx101 4% increased until 8–14 hours (median t max value) on days 1, 12, and 21 • figure 2 shows a comparison of mean plasma minocycline concentrations during the first 24 hours after a single dose of oral minocycline and after topical applications of fmx101 4% at 3 timepoints in adult subjects • in adult subjects, oral minocycline treatment had a geometric mean c max of 850 ng/ml, while topical application of 4 g fmx101 4% in adults had a geometric mean c max ranging from 1.109–1.539 ng/ml (days 1-2, days 12-13, and days 21-25) • steady state was achieved on day 6 of treatment figure 2. mean plasma minocycline concentration over the first 24 hours following a single dose of oral minocycline and topical application of fmx101 4% (semi-log scale) in adult subjects (study fx2014-03) • in adults, minocycline exposure with daily topical application of fmx101 4% for 21 days was 730 to 765 times lower than that with oral minocycline (table 3) table 3. summary of minocycline relative bioavailability with oral minocycline administration (reference) and topical application of fmx101 4% (test) at day 12 and day 21 (study fx2014-03) fmx101 4% vs oral minocycline n geometric meana geometric lsm test/reference ratio,b % (90% ci) 1/gmr fmx101 4% (test) oral minocycline (ref) day 12 c max 29 1.06 846 0.126 (0.100, 0.159) 794 day 21 c max 30 1.11 850 0.131 (0.113, 0.151) 763 day 12 aucc 29 20.06 14976 0.134 (0.110, 0.163) 746 day 21 aucd 30 20.07 15060 0.137 (0.121, 0.156) 730 ªgeometric mean of oral minocycline and fmx101 4% based on lsm. bgeometric lsm ratio and the associated 90% ci were back-transformed point estimates and the associated 90% ci. cday 12 auc 0-tau for fmx101 4% vs auc 0-inf for oral minocycline. dday 21 auc 0-tau for fmx101 4% vs auc 0-inf for oral minocycline. ci=confidence interval; lsm=least squares mean; gmr=geometric mean ratio. pharmacokinetics – pediatrics • in pediatric subjects, the overall plasma concentrations of minocycline following the application of fmx101 4% once daily for 7 days were relatively constant over day 7 (~2.5 ng/ml) (figure 3) figure 3. mean plasma concentrations of minocycline following application of fmx101 4% once daily for 7 days in pediatric subjects (study fx2016-21) -5 0 5 10 15 20 25 0 3 12 16 24 pl as m a m in oc yc lin e c on ce nt ra tio n (n g/ m l) ± sd hours post-day 7 administration 9 11 years 12 14 years 15 16 years, 11 months overall lloq lloq=lower limit of quantification; sd=standard deviation. • there were no substantial differences in mean concentrations of minocycline among the 3 pediatric cohorts (table 4) – across all cohorts, the geometric mean c max value was 2.4 ng/ml table 4. pharmacokinetic parameters of minocycline in plasma in pediatric acne subjects treated with fmx101 4% (study fx2016-21) age group n geometric mean t max (hr)ac max (ng/ml) auc 0-tau (ng*hr/ml) c 24 (ng/ml) 9–11 years 6 3.522 68.175 2.933 12 (0,24) 12–14 years 8 2.250 42.167 1.998 20 (0,24) 15–16 years, 11 months 6 1.735 35.067 1.302 6 (0,24) overall 20 2.381 46.087 1.972 12.1 (0,24) amedian (minimum, maximum) shown for t max . safety • in both adult and pediatric subjects, daily application of fmx101 4% was found to be safe and well tolerated (table 5) – no adult or pediatric subjects experienced a serious treatment-emergent adverse event (teae), treatment-related teaes, or a teae leading to withdrawal from the study – 9 adult subjects in the fmx101 4% group reported 1 or more teaes; all were mild or moderate in intensity (fx2014-03) – a single pediatric subject experienced 2 unrelated teaes (nausea and vomiting) (fx2016-21) table 5. overall summary of teaes following administration of oral minocycline and topical application of fmx101 4% in adult and pediatric subjects adult study (fx2014-03) pediatric study (fx2016-21)   oral minocycline (n=30) fmx101 4% (n=30) fmx101 4% (n=20) subjects with any teae, n (%) 2 (6.7) 9 (30.0) 1 (5.0) dysmenorrhea 0 2 (6.7) nasal congestion 0 2 (6.7) rhinorrhea 0 2 (6.7) asthma 0 1 (3.3) bronchitis 0 1 (3.3) cough 1 (3.3) 0 dermatitis contact 0 1 (3.3) headache 1 (3.3) 0 oropharyngeal pain 0 1 (3.3) pharyngitis streptococcal 0 1 (3.3) respiratory tract congestion 0 1 (3.3) tonsillitis 0 1 (3.3) nausea 1 (5.0) vomiting 1 (5.0) pharmacokinetic evaluation of once-daily topical 4% minocycline foam in adult and pediatric subjects with moderate-to-severe acne in two phase 1 studies terry m. jones, md1; herman ellman, md2; tina devries, phd2 1j&s studies, inc., college station, texas, usa; 2foamix pharmaceuticals, inc., bridgewater, new jersey, usa references 1. picardo m, et al. dermatol ther (heidelb). 2017;7:43-52. 2. zaenglein al, et al. j am acad dermatol. 2016;74:945-973. 3. shemer a, et al. j am acad dermatol. 2016;74:1251-1252. disclosure: foamix pharmaceuticals, inc., sponsored this study. conclusions • in adult subjects, mean minocycline auc and c max values were substantially lower following the daily topical application of 4 g fmx101 4% for 21 days in comparison with a single dose of oral minocycline (~1 mg/kg) • there was no evidence of accumulation in adult subjects receiving daily topical application of fmx101 4% for up to 21 days • in pediatric subjects, mean minocycline cmax and auc values following the daily topical application of 4 g fmx101 4% for 7 days were 2.4 ng/ml and 46.1 ng*hr/ml, respectively; these values were comparable to those seen in adults, 1.5 ng/ml and 20.1 ng*hr/ml, respectively, indicating similar minimal systemic exposure • pediatric subjects in all 3 age cohorts had similar levels of minocycline (~2.5 ng/ml) across the dosing interval with daily application of fmx101 4% for 7 days • once-daily topical application of fmx101 4% for 7 days and 21 days was shown to be safe and well tolerated in pediatric and adult subjects, respectively acknowledgment: p-value communications provided editorial support. fc17posterfoamixjonespharmacokineticeval.pdf skin july 2019 volume 3 issue 4 copyright 2019 the national society for cutaneous medicine 275 brief articles isotretinoin induced nail fold pyogenic granuloma resolution with combination therapy: a case report and review of the literature. jonathan g. bellew, do1,2,3; chad taylor, do3; jaldeep daulat, do3; vernon t. mackey, do1 1advanced desert dermatology 2midwestern university 3mohave centers for dermatology and plastic surgery pyogenic granulomas represent vascular hyperplasias of unknown etiology.[1] they are characterized by rapid growth with friability and associated pain. morphologically they present as a solitary red papule, polyp, or nodule that frequently ulcerates and bleeds excessively with minor trauma. they may develop at any age but are more common in children and adolescents.[1] although idiopathic, approximately one-third develop after trauma. most common sites include the gingiva, fingers, lips, face and tongue.[2] pyogenic granulomas have been reported in association with systemic retinoids,[3] indinavir, and epidermal growth factor receptor inhibitors. other associations include fluctuating hormonal states such as during pregnancy or with oral contraceptive treatment.[1] we present a case of eruptive pyogenic granulomas of the peri-ungal fingers in an adolescent male undergoing systemic retinoid therapy for severe recalcitrant nodulocystic acne, highlighting this important but rarely reported adverse effect of systemic isotretinoin therapy. a 15-year-old male presented to our dermatology clinic with multiple painful bright red papulonodules located at the dorsal surface of the distal portion of the peri-ungal third and fourth fingers extending from the hyponychium distally down through the nail grooves with extension proximally to the pyogenic granulomas are vascular hyperplasias presenting as red papules, polyps, or nodules on the gingiva, fingers, lips, face and tongue of children and young adults. most commonly they are associated with trauma, but systemic retinoids have rarely been implicated as a causative factor in their appearance. we present a case of spontaneous eruption of multiple pyogenic granulomas of the bilateral peri-ungal fingers in an otherwise healthy adolescent male undergoing isotretinoin therapy for severe nodulocystic acne. these pyogenic granulomas did not resolve spontaneously with discontinuation of isotretinoin, or first line therapeutic modalities. their resolution did occur with administration of intralesional steroids and ablation with silver nitrate. abstract introduction case report skin july 2019 volume 3 issue 4 copyright 2019 the national society for cutaneous medicine 276 figure 1. multiple painful papulonodules at the distal bilateral nail folds of the fingernails. figure 2. pyogenic granulomas improving two weeks following discontinuation of isotretinoin therapy. figure 3. resolution of pyogenic granulomas two months post discontinuation of isotretinoin and successful treatment with intralesional triamcinolone and topical silver nitrate. bilateral portion of the nail walls (figure 1). the lesions appeared abruptly and were enlarging over several weeks. associated pain with easy bleeding on minor trauma was reported in the lesions. the patient denied significant trauma or prior contact with chemicals or allergens before the outbreak. his primary care provider initiated treatment with trimethoprim-sulfamethoxazole twice daily for two weeks. after the patient experienced no significant response to therapy, he was referred to our dermatology office for evaluation. at the time of the peri-ungal eruption on the distal fingernails, the patient was undergoing isotretinoin therapy for severe nodulocystic acne with significant scarring. he was in his fifth month of isotretinoin therapy with a cumulative dose of 140 mg/kg. he began isotretinoin therapy at a dose of 40 mg daily (0.52 mg/kg/day) for the first month and his dose later increased to 80 mg daily (1.04 mg/kg/day). prior to undergoing isotretinoin therapy the patient was treated for three months with topical benzoyl peroxide, tretinoin, clindamycin, and oral doxycycline without clinically significant improvement. monthly laboratory evaluations during isotretinoin therapy were within normal range with no abnormalities in the hematopoietic, renal, or hepatic systems. the patient’s nodulocystic acne was much improved after five months of isotretinoin therapy having reached the targeted cumulative isotretinoin dose between 120 to 150 mg/kg, thus we elected to discontinue this medication in light of the patient’s painful eruption on the distal peri-ungal nails. local treatment to the fingernails was initiated with topical mupirocin 2% ointment in the morning and ketoconazole 2% cream at night to prevent secondary infection. two weeks later at follow-up, the patient exhibited smaller peri-ungal lesions with improved mobility and less pain (figure 2). one month after discontinuation of isotretinoin the lesions persisted. intralesional triamcinolone skin july 2019 volume 3 issue 4 copyright 2019 the national society for cutaneous medicine 277 injections (2.5 mg/ml), administered two weeks apart over six weeks followed by a single treatment of topical silver nitrate subsequently resolved the lesions (figure 3). excess granulation tissue and pyogenic granulomas have been described in both previous acne scars and peri-ungal locations.[4] literature review illustrates rare reports of this adverse event.[4,5] in addition, the mechanism by which retinoids cause excess granulation tissue of the skin is not well known. a course of occlusive therapy with topical steroids and antibiotics under occlusion for two to three weeks is the first line treatment for peri-ungal pyogenic granulomas.[5] in our patient’s case, local treatment with topical antimicrobials along with discontinuation of oral isotretinoin was ineffective in resolving the painful nailfold pyogenic granulomas. due to the severity and extent of this patient’s pyogenic granulomas, intralesional steroids were chosen rather than topical steroids. intralesional triamcinolone and silver nitrate over a period of six weeks led to complete resolution of these irritating lesions. in 1983, campbell et al. first reported the association between systemic retinoid therapy and excess granulation tissue in patients being treated for cystic acne and psoriasis.[3] at that time, campbell felt that the response was idiosyncratic and unrelated to either the daily dose of retinoid or the total cumulative dose. the available literature to date supports the occurrence of excess granulation tissue within existing acne lesions, but an even rarer occurrence has been the association of systemic retinoid therapy and excessive granulation tissue occurring at non-acne locations such as the nail folds of the fingers and toes.[6] it has been reported that the resolution of excess granulation tissue secondary to systemic retinoid therapy occurs on withdrawal of isotretinoin.[7] unfortunately for our patient, discontinuation of isotretinoin and prevention of secondary infection in areas of excess granulation tissue was insufficient in resolving these lesions. to date, there is no consensus evidence based approach to the treatment of isotretinoin induced pyogenic granulomas. literature supported first line medical treatment for pyogenic granulomas includes topical high potency corticosteroids such as clobetasol under occlusion.[8] surgical treatment of pyogenic granulomas includes shave excision with electrodessication and curettage, pulsed dye laser, and sclerotherapy utilizing monoethanolamine oleate.[9,10] ultimately a combination of intralesional corticosteroids with silver nitrate therapy resulted in complete resolution of peri-ungal pyogenic granulomas in our patient. we hope that this case report will assist others in the future recognition and management of this rare but painful adverse effect of oral retinoid therapy for severe nodulocystic acne. conflict of interest disclosures: none. funding: none. corresponding author: jonathan g. bellew, advanced desert dermatology peoria, az jonathanbel@pcom.edu conclusion discussion skin july 2019 volume 3 issue 4 copyright 2019 the national society for cutaneous medicine 278 references: 1. bolognia jl, jorizzo jl, schaffer jv, eds. dermatology. third edition. vol 2. elsevier saunders; 2012;1922-1923. 2. kerr da. granuloma pyogenicum. oral surg oral med oral pathol. 1951;4:158. 3. campbell jp, grekin rc, ellis cn, et al. retinoid therapy is associated with excess granulation tissue responses. j am acad dermatol. 1983;9:708-713. 4. exner jh, dahod s, pochi pe. pyogeniclike acne lesions during isotretinoin therapy. arch dermatol. 1983;119:808-811. 5. piraccini bm, bellavista s, misciali c, torti a, de berker d, richert b. periungal and subungal pyogenic granuloma. br j dermatol. 2010;163:941-953. 6. shalita ar, cunningham wj, leyden jj, et al. isotretinoin treatment of acne and related disorders: an update. j am acad dermatol. 1983;4:629-638. 7. figueiras da, ramos tb, marinho ak, bezerra ms, cauas rc. paronychia and granulation tissue formation during treatment with isotretinoin. an bras dermatol. 2016;91(2):223-225. 8. miller ra, ross jb, martin j. multiple granulation tissue lesions occurring in isotretinoin treatment of acne vulgaris – successful response to topical corticosteroid therapy. j am acad dermatol. 1985;12:888-889. 9. tay yk, weston wl, morelli jg. treatment of pyogenic granulomas in children with the flashlamp-pumped pulsed dye laser. pediatrics. 1997;99:368-370. 10. matsumoto k, nakanishi h, seike t, et al. treatment of pyogenic granuloma with a sclerosing agent. dermatol surg. 2001;27:521-523. microsoft word 10. 621 proof done.docx skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 68 brief articles a rare case of dermatitis herpetiformis presenting as fingertip petechiae amy weiss, md,1 shiri nawrocki, ba,2 ana cristina laureano, md,3 sharon scherl, md,3 kenneth shulman, md,4 eun ji kwon, md4 1robert wood johnson medical school, department of dermatology, somerset, nj 2rutgersrobert wood johnson medical school, piscataway township, nj 3scherl dermatology, tenafly, nj 4dermpath diagnostics new york, port chester, ny dermatitis herpetiformis (dh) is an infrequent inflammatory autoimmune cutaneous disorder usually accompanied by glutensensitive enteropathy (celiac disease [cd]). patients with dh commonly present with pruritic, polymorphic lesions, primarily consisting of grouped erythematous papules and urticarial plaques with vesicles or blisters symmetrically distributed on the extensor surfaces of the elbows, forearms, buttocks, and knees, and sometimes involving the scalp. we describe a rare case of a patient presenting with fingertip petechiae as the only initial manifestation of dh. only six cases of acral petechial lesions as the sole initial presenting sign of dh in adult patients have been described in the literature.1-6 because dh is often the first presenting sign of cd, dermatologists should be aware of this unusual clinical presentation. a 36-year-old well-developed, well-nourished woman presented with a 4-month history of recurrent flares of painful petechiae involving several fingertips. the lesions tended to follow along dermatoglyphic lines (figure 1a). the remainder of her skin examination introduction case report dermatitis herpetiformis (dh) is an uncommon inflammatory autoimmune disease that most commonly presents as a pruritic, papulovesicular eruption in young children and adolescents. it follows a chronic and relapsing course and usually involves extensor surfaces of the elbows, forearms, buttocks, and knees and can also involve the scalp. dh is usually accompanied by gluten-sensitive enteropathy (celiac disease). in most patients with dh, the enteropathy is asymptomatic. dh is usually a life-long condition that requires continued treatment, including dapsone and elimination of gluten from the diet. we describe a rare case of a patient who presented with fingertip petechiae as the only initial manifestation of dh. dh should be considered in the differential diagnosis of petechiae of the fingertips, even if it is the only presenting sign. abstract skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 69 was initially unremarkable, including normal nail units. the patient’s remaining physical examination and review of systems were unrevealing. her extensive laboratory evaluation, including coagulation studies, complete blood count, serum cryoglobulin, plasma cryofibrinogen, and transthoracic echocardiogram, was negative. punch biopsy of a petechial lesion on her thumb (figure 1b and 1c) demonstrated infiltration of neutrophils within the dermal papillae and subepidermal clefting. there was also a perivascular mixed inflammatory cell infiltrate with rare nuclear dusting and few extravasated erythrocytes in the superficial dermis. there was no evidence of vasculitis. acid-fast bacilli, fite, gram, and periodic acid-schiff stains were negative for mycobacterial, bacterial, or fungal organisms. a perilesional direct immunofluorescence study (figure 1d) demonstrated granular deposition of immunoglobulin a (iga) in the dermal papillae and at the basement membrane zone. some deposition of iga was also found surrounding the superficial blood vessels. no deposition of other immunoreactants was found within the epidermis, basement membrane zone, vessels, or dermis. the histologic and immunofluorescence findings were consistent with dh. the patient subsequently underwent additional testing for antibody markers and genetic testing for cd. autoantibodies to endomysium, tissue transglutaminase, and deaminated gliadin were not present. furthermore, the patient demonstrated no heterodimers for hla-dq2 or hla-dq8. nevertheless, given the confirmed diagnosis of dh and its close association with cd, the patient underwent esophagogastroduodenoscopy. duodenal biopsies showed minimal villous blunting with increased intraepithelial lymphocytes within villous tips, consistent with cd. six weeks after her initial presentation, the patient presented with grouped pruritic vesiculopapules on both elbows and forearms (figure 2a). she also presented with erythematous and crusted papules along the sides of her fingers (figure 2b). another biopsy sample obtained from the right forearm showed collections of neutrophils demonstrating slight nuclear dusting within dermal papillae, also consistent with dh (figure 2c). the patient was started on a gluten-free diet, which has kept her cutaneous symptoms under good control. she declined the standard dapsone regimen treatment but opted for small doses of dapsone when flareups occurred. figure 1. dermatitis herpetiformis. initial presentation. clinical findings – (a) fingertip petechiae along dermatoglyphic lines; (b) light microscopy of a lesional punch biopsy specimen subepidermal vesiculation and collections of neutrophils within dermal papillae (40x); (c) perivascular mixed inflammatory cell infiltrate including neutrophils and rare nuclear dusting. numerous extravasated erythrocytes (100x); (d) perilesional direct immunofluorescence study granular deposition of iga in dermal papillae and at the basement membrane zone. deposition of iga about superficial blood vessels (100x). skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 70 figure 2. dermatitis herpetiformis. six weeks after initial presentation. (a) grouped pruritic vesiculopapules on bilateral elbows and forearms; (b) erythematous and crusted papules along the sides of the fingers; (c) light microscopy of a specimen obtained from the right forearm collections of neutrophils demonstrating slight nuclear dusting within dermal papillae (200x). dh is an autoimmune vesiculobullous disorder that classically presents with intensely pruritic grouped erythematous papules and urticarial plaques with vesicles or blisters. often the initial lesions turn into erosions and excoriations due to chronic pruritus. typically, the lesions are symmetrically distributed on the extensor surfaces of the elbows, knees, shoulders, midline of back, buttocks, and sacral region, although they can also involve the face, scalp, nuchal area, and groin.7 petechiae or purpuric macules on the fingers or palmoplantar surfaces are uncommon presentations of dh and are more likely to occur in children.7 only six adult cases of dh presenting with acral petechiae or purpura as the sole initial presenting sign have been described in the literature.1-6 in our case, the initial and only manifestation was petechiae involving the fingertips. more classicappearing lesions of dh developed in our patient’s elbows and forearms at the 6-week follow-up visit. dh is histologically characterized by collections of neutrophils in the dermal papillae with subepidermal blister formation. on direct immunofluorescence, there are granular depositions of iga within the dermal papillae and/or along the dermo-epidermal junction. these histologic and immunofluorescence findings were also observed in cases presenting with acral petechiae or purpuric lesions, with some cases demonstrating extravasated red blood cells in the upper dermis.1,3,8-10 while one case presented with leukocytoclastic vasculitis on light microscopic examination, no deposition of immunoreactants was found along the blood vessels on direct immunofluorescence.11 in our case, numerous extravasated erythrocytes were found in the papillary dermis that accounted for the petechial appearance. while some iga deposition was noted along the small blood vessels on direct immunofluorescence in our case, it was interpreted as secondary to dh rather than to a vasculitic process, as no light microscopic evidence of vasculitis was detected and the patient soon proceeded to present with classic, nonpurpuric lesions of dh. dh is usually accompanied by cd, an autoimmune response against gliadin, tissue transglutaminase, and epidermal transglutaminase induced by gluten ingestion.4 the typical presentation of cd is characterized by gastrointestinal signs and symptoms, and typical diagnostic testing discussion skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 71 includes serologic screening (e.g., anti-tissue transglutaminase and anti-endomysial iga antibodies) and genetic testing for human leukocyte antigens (hla-dq2 and hladq8) that are strongly associated with cd. when extraintestinal manifestations of cd exist, as occurs in patients with dh, minimal or absent gastrointestinal signs/symptoms may occur,12 such as in our patient. this case had an atypical presentation of dh; she lacked clinical signs/symptoms of cd and tested negatively for screening serologies and for the hla heterodimers, hla-dq2, and hla-dq8. without the confirmation of her dh diagnosis by histologic and immunofluorescence evaluation, the patient probably would not have undergone a small bowel biopsy, and detection of her underlying cd would likely have been delayed. the diagnosis of dh can be difficult without the classic presentation. a rapid diagnosis of dh can vastly improve the quality of life of patients with undiagnosed cd, because gastrointestinal and cutaneous symptoms can be resolved with a gluten-free diet. this case strongly emphasizes that dh should be included in the differential diagnosis of petechial involvement of the hands and fingers. keywords: dermatitis herpetiformis, celiac disease, gluten-sensitive enteropathy; autoimmune disease, direct immunofluorescence. abbreviations: dh dermatitis herpetiformis; cd celiac disease; iga immunoglobulin a conflict of interest disclosures: none funding: none corresponding author: shiri nawrocki rutgersrobert wood johnson medical school, piscataway township, nj 18 porter avenue, tenafly, nj tel: 201-694-8733 fax: 201-894-1574 email: shiri.nawrocki@gmail.com references: 1. tu h, parmentier l, stieger m, et al. acral purpura as leading clinical manifestation of dermatitis herpetiformis: report of two adult cases with a review of the literature. dermatology. 2013;227(1):1-4. 2. zaghi d, witheiler d, menter am. petechial eruption on fingers. dermatitis herpetiformis. jama dermatology. 2014;150(12):1353-1354. 3. flann s, degiovanni c, derrick ek, munn se. two cases of palmar petechiae as a presentation of dermatitis herpetiformis. clin exp dermatol. 2010;35(2):206-208. 4. hofmann sc, nashan d, bruckner-tuderman l. petechiae on the fingertips as presenting symptom of dermatitis herpetiformis duhring. j eur acad dermatol venereol. 2009;23(6):732-733. 5. lopez aventin d, ilzarbe l, herrero-gonzalez je. recurrent digital petechiae and weight loss in a young adult. gastroenterology. 2013;144(7):e1011. 6. perez-garcia mp, mateu-puchades a, sorianosarrio mp. a 26-year-old woman with palmar petechiae. int j dermatol. 2013;52(12):1493-1494. 7. bonciolini v, bonciani d, verdelli a, et al. newly described clinical and immunopathological feature of dermatitis herpetiformis. clin dev immunol. 2012;2012:967974. 8. mcgovern tw, bennion sd. palmar purpura: an atypical presentation of childhood dermatitis herpetiformis. pediatr dermatol. 1994;11(4):319322. 9. pierce dk, purcell sm, spielvogel rl. purpuric papules and vesicles of the palms in dermatitis herpetiformis. j am acad dermatol. 1987;16(6):1274-1276. 10. massone l, borghi s, pestarino a, piccini r, gambini c. dermatitis herpetiformis: a case with palmar purpuric lesions treated with disodium cromoglycate. j am acad dermatol. 1988;19(3):577. 11. naylor e, atwater a, selim ma, hall r, puri pk. leukocytoclastic vasculitis as the presenting feature of dermatitis herpetiformis. arch dermatol. 2011;147(11):1313-1316. 12. setty m, hormaza l, guandalini s. celiac disease: risk assessment, diagnosis, and monitoring. mol diagn ther. 2008;12(5):289-298. fc21_fitzpatrickposter_09.23.21 pooled results of vp-102 safety and efficacy in phase 3 trials for molluscum contagiosum by fitzpatrick skin type (fst) elaine siegfried md,1 lawrence f. eichenfield md,2 pearl kwong md,3 seemal r. desai md,4,5 susan cutler,6 cynthia willson,6 pamela rumney,6 christine crosby,6 jennifer andres,6 mark mcbride7 1st. louis university, st. louis, mo; 2uc san diego and rady children’s hospital, san diego, ca; 3solutions through advanced research, jacksonville, fl; 4department of dermatology, the university of texas southwestern medical center, dallas, texas; 5innovative dermatology, plano, texas; 6verrica pharmaceuticals inc, west chester, pa; 7instat consulting, inc., chatham, nj. • vp-102, a single-use proprietary drug-device combination product (cantharidin 0.7%), is under investigation for treatment of molluscum contagiosum (mc). in 2 phase 3 trials, 528 subjects ≥ 2 years with mc, were randomized (3:2) to receive topical application of vp-102 or vehicle. • while most subjects were caucasian vp-102:vehicle (n=277:202 [89.4%:92.7%]), there was representation across all fsts. fst is a tool which assesses skin burn propensity during phototherapy but can be misused to imply constitutive skin color/ethnicity.1 • skin of color patients with molluscum often experience pigmentary changes with or without treatment. however, fst has not been captured in molluscum treatment trials. • this post hoc analysis was designed to assess vp-102 efficacy (subjects achieving complete clearance (cc) (%)) and safety by fst group, compared to the overall study population. • vp-102 or vehicle was applied to all baseline and new lesions once every 21 days until cc, or up to 4 applications. • subjects were evaluated at days 21, 42, 63, 84. • treatment emergent adverse events (teaes) were assessed throughout the study. introduction methods disclosures the studies were sponsored by verrica pharmaceuticals inc. editorial support was provided by versant learning solutions and funded by verrica pharmaceuticals inc. the authors have received the following from verrica pharmaceuticals: e. siegfried: h, c; lf eichenfield: h, c, s. p. kwong: h, c; s. desai: consultant; s. cutler: e; c. willson: e; p. rumney: e; c. crosby: e; j. andres: e; m. mcbride: consultant. h=honoraria; c=clinical funds; s=stocks; e=employee. conclusion • vp-102 was safe and effective across all fitzpatrick skin type groups, consistent with results from the overall study population. references 1. ware o et.al. racial limitations of fitzpatrick skin type. cutis. 2020;105: 77-80. 2. eichenfield l et.al. pooled results of two randomized phase iii trials evaluating vp-102, a drug-device combination product containing cantharidin 0.7% (w/v) for the treatment of molluscum contagiosum. am j clin dermatol. 2021. mar;22(2): 257-265. demographics & medical histories results baseline characteristics molluscum medical histories 0% 10% 20% 30% 40% 50% 60% 5.9 7.8 16.7 5.1 1.9 10.9 19.9 19.0 7.6 5.8 5.7 25.7 34.3 23.8 15.2 6.7 11.4 50.6 52.4 25.7 vp-102: type i or ii vehicle: type i or ii vehicle: type iii or iv vehicle: type v or vi vp-102: type iii or iv vp-102: type v or vi 13.9 13.5 48.5 0.0 visit 2 (day 21) visit 3 (day 42) visit 4 (day 63) eos visit (day 84) co m pl et e cl ea ra nc e (% ) eos=end of study. • a significantly higher percentage of subjects achieved cc in the vp-102 group than with vehicle at day 84; vp-102 vs. vehicle (50% vs. 15.6%) (p<0.0001). • mean percent change from baseline in mc lesion counts decreased 76% for vp-102 and 0.3% for vehicle at day 84 (p<0.0001). • the most common teaes in the vp-102 group were application site blistering, pruritus, pain, and erythema, which were generally mild or moderate in severity.2 eos=end; ert=evaluation of response to treatment. dermatology exam treatment applicationert camp 1 (n=266) & two randomized, vehicle-controlled, double-blind phase 3 trials 12 weeks, vp-102:vehicle (3:2 randomization) vp-102 camp 1 n=160 camp 2 n=150 vehicle camp 1 n=106 camp 2 n=112 visit 1 (day 1) visit 2 (day 21) +24-hrs visit visit 3 (day 42) visit 4 (day 63) eos visit (day 84) camp 2 (n=262) vp-102 (n=311) vehicle (n=216) age (years) mean (sd) 7.5 (6.7) 6.8 (5.8) median (range) 6.0 (2–60) 6.0 (2–54) male 156 (50.2) 111 (51.4) race or ethnic group no. (%) white 277 (89.1) 201 (93.1) black or african american 14 (4.5) 7 (3.2) asian 6 (1.9) 1 (0.5) american indian/alaskan native 0 1 (0.5) other 14 (4.5) 6 (2.8) gender no. (%) fitzpatrick skin type no. (%) ii i iii iv v vi 20 (6.5) 81 (26.1) 8 (3.7) 71 (32.6) 97 (31.3) 69 (22.3) 70 (32.1) 34 (15.6) 33 (10.6) 9 (2.9) 32 (14.7) 3 (1.4) vp-102 (n=311) vehicle (n=216) baseline lesion count mean (sd) 20.4 (23.0) 22.6 (22.3) median (range) 12.0 (1–184) 16.0 (1–110) atopic dermatitis (ad) no. (%) history or active ad 50 (16.1) 35 (16.2) active ad* 23 (7.4) 20 (9.3) complete lesion clearance by fitzpatrick skin type (pooled iit population) • study included 180 subjects with fst i or ii (n=101 vp-102; n=79 vehicle), 270 with fst iii or iv (n=166 vp-102; n=104 vehicle), and 77 with fst v or vi (n=42 vp-102; n=35 vehicle). • cc of mc lesions across fst groups was 48.5%, 50.6%, 52.4% for types i/ii, iii/iv, and v/vi when treated with vp-102 and 13.9%, 13.5%, and 25.7% in vehicle group, respectively (p<0.0001 for types i/ii and iii/iv, and p=0.0008 for type v/vi). • the incidence of teaes by fst subgroup was similar to the overall study population. powerpoint presentation 0 20 40 60 80 100 0 1 2 4 6 8 12 m c id in d lq i, % p at ie nt s† synopsis • il-17a and il-17f are pro-inflammatory cytokines that share ~50% structural homology and overlapping biological function.1–3 both il-17a and il-17f are expressed at sites of inflammation4,5 and independently co-operate with other cytokines to mediate inflammation4 (figure 1) • dual neutralization of il-17a and il-17f in disease-relevant human cellular systems resulted in lower expression of inflammation-linked genes and pro-inflammatory cytokines as well as greater suppression of immune cell migration when compared with il-17a blockade alone4 • bimekizumab, a monoclonal igg1 antibody, potently and selectively neutralizes the biological function of both il-17a and il-17f4,6,7 references 1yang et al, j exp med 2008;1063–1075; 2hymowitz et al, embo 2001;20:5332–5341; 3chu, targeting the il-17 pathway in inflammatory disorders 2017, adis; 4glatt et al, ann rhem dis 2018;77:523–532; 5van baarsen et al. arthritis res & ther 2014;16:426; 6glatt et al, br j clin pharm 2017;83:991–1001; 7papp et al, jaad 2018;doi: 10.1016/j.jaad.2018.03.037 disclosures, funding, and acknowledgements this study was funded by ucb pharma ka papp has received consultant fees from astellas, astrazeneca, baxalta, baxter, boehringer ingelheim, bristol-myers squibb, canfite, celgene, coherus, dermira, dow pharma, eli lilly, forward pharma, galderma, genentech, janssen, kyowa hakko kirin, leo pharma, meiji, seika pharma, msd, merck serono, mitsubishi pharma, novartis, pfizer, regeneron, roche, sanofi/genzyme, takeda, ucb, and valeant; investigator fees from astellas, baxalta, boehringer ingelheim, bristol-myers squibb, celgene, coherus, dermira, dow pharma, eli lilly, galderma, genentech, gsk, janssen, kyowa hakko kirin, leo pharma, medimmune, msd, merck-serono, novartis, pfizer, regeneron, roche, sanofi/genzyme, takeda, ucb, and valeant; speaker fees from astellas, celgene, eli lilly, galderma, kyowa hakko kirin, leo pharma, msd, novartis, pfizer, and valeant; has participated in advisory boards for astellas, baxter, boehringer ingelheim, bristol-myers squibb, celgene, dow pharma, eli lilly, galderma, janssen, msd, novartis, pfizer, regeneron, sanofi/genzyme, ucb, and valeant; is a steering committee member for boehringer ingelheim, celgene, eli lilly, janssen, kyowa hakko kirin, msd, merck-serono, novartis, pfizer, regeneron, sanofi/genzyme, and valeant; and is a scientific officer for kyowa hakko kirin. jf merola has received honoraria from abbvie, celgene, eli lilly, janssen, novartis, pfizer, samumed and ucb. ab gottlieb has received consultant fees, advisory board fees or speaker bureau fees from janssen inc.; celgene corp., bristol myers squibb co., beiersdorf, inc., abbvie, ucb, novartis, incyte, lilly, reddy labs, valeant, dermira, allergan, sun pharmaceutical industries; and research grants from janssen, incyte, lilly, novartis, allergan, leo. cem griffiths has received grants and personal fees from abbvie, celgene, leo, lilly, janssen, novartis, pfizer, and ucb pharma; grants from sandoz; personal fees from almirall and galderma. cg has received research grants from abbvie, celgene, novartis, eli lilly, janssen, sandoz, pfizer, leo, and ucb. kk harris, n cross, l peterson and c cioffi are employees of ucb. l peterson and c cioffi hold ucb stock or stock options. a blauvelt has received consultant fees from eli lilly and company, janssen, regeneron, and sanofi genzyme; and a scientific adviser and/or clinical study investigator for abbvie, aclaris, allergan, almirall, amgen, boehringer ingelheim, celgene, dermavant, dermira, inc., eli lilly and company, genentech/roche, glaxosmithkline, janssen, leo, merck sharp & dohme, novartis, pfizer, purdue pharma, regeneron, sandoz, sanofi genzyme, sienna pharmaceuticals, sun pharma, ucb pharma, valeant, and vidac. the authors would like to acknowledge alexandra webster, msc, of imed comms, an ashfield company, for medical writing support that was funded by ucb pharma in accordance with good publication practice (gpp3) guidelines. dual neutralization of il-17a and il-17f with bimekizumab improves quality of life in patients with moderate-to-severe plaque psoriasis: results from a phase 2b study and correlation with clinical response kim a. papp1, joseph f. merola2, alice b. gottlieb3, christopher e.m. griffiths4, kristina k. harris5, nancy cross6, luke peterson6, christopher cioffi7, andrew blauvelt8 1probity medical research and k papp clinical research, waterloo, on, canada; 2harvard medical school, brigham and women's hospital, boston, ma, usa; 3new york medical college, metropolitan hospital, new york, ny, usa; 4dermatology centre, university of manchester, manchester, uk; 5ucb pharma, hong kong, china; 6ucb biosciences inc., raleigh, nc, usa; 7ucb pharma, brussels, belgium; 8oregon medical research center, portland, or, usa 37th fcd conference 18–21 october 2018 las vegas, nv, usa conclusion • dual neutralization of il-17a and il-17f with bimekizumab in patients with moderate-to-severe plaque psoriasis was associated with rapid onset of clinically meaningful efficacy, with no unexpected safety findings • bimekizumab treatment also resulted in rapid improvements in disease-specific quality of life measures in the majority of patients, which correlated with clinical response • these data support achievement of high levels of skin clearance (absolute pasi ≤2) being associated with superior improvements in disease-specific hrqol weeks figure 4a. mcid, 3x mcid and 4x mcid in dlqi at week 12; figure 4b. mcid in dlqi by visit in patients with baseline dlqi ≥4, full analysis set (observed values); *percentages calculated based on total numbers of evaluable patients at week 12; †percentages calculated based on total numbers of evaluable patients at each visit figure 5a. dlqi of 0 or 1 by absolute pasi at week 12; figure 5b. dlqi of 0 or 1 by bsa affected by psoriasis at week 12; combined bimekizumab dose group, full analysis set (observed values); *percentages calculated based on total numbers of evaluable patients at week 12 in the pooled bimekizumab group, patients with lower absolute pasi (≤2) more frequently achieved dlqi of 0 or 1 versus those with higher absolute pasi at week 12 (figure 5a); similar results were observed at week 12 in patients with lower bsa versus higher bsa involvement (figure 5b) figure 1. dual neutralization of il-17a and il-17f in immune-mediated inflammatory diseases results at the individual patient level, rapid improvements were observed in absolute pasi over time for those receiving bimekizumab. by week 12, in the three highest bimekizumab dose groups almost all patients had an absolute pasi <2 with the majority of patients at or near zero (figure 3); pasi improvements were correlated with reductions in dlqi, with the majority of patients achieving a dlqi of 0 or 1 (no impact of psoriasis on disease-specific hrqol) at week 12 (figure 3) all or nearly all patients with baseline dlqi ≥4 achieved mcid in dlqi at week 12 in the top three bimekizumab dose groups; 3x mcid and 4x mcid were also achieved by a substantially greater percentage of bimekizumab patients with baseline dlqi ≥12 and ≥16, respectively, compared with placebo (figure 4a). mcid in dlqi was achieved rapidly and differentiated from placebo after first dose across all bimekizumab groups (figure 4b) bkz 64 mg; n=33 bkz 160 mg; n=37 bkz 320 mg; n=37 bkz 160 mg (320 mg ld); n=34 bkz 480 mg; n=31 a) b) 79.6 53.6 64.3 52.5 0 20 40 60 80 100 ≤1 >1 – ≤3 >3 – ≤5 >5 dlqi of 0 or 1, % patients* b s a a ff ec te d by p so ri as is b) n=40 n=14 n=28 n=108 77.7 73.9 51.7 29.4 0 20 40 60 80 100 ≤1 >1 – ≤2 >2 – ≤5 >5 dlqi of 0 or 1, % patients* a bs ol ut e pa s i absolute pasi in bimekizumab-treated patients bsa affected by psoriasis in bimekizumab-treated patients a) n=17 n=29 n=23 n=121 0 20 40 60 80 100 0 2 4 6 8 10 12 pa s i1 00 r es po ns e, % ( s e ) of p at ie nt s 28.2%** 27.9%*** 48.8%*** 60.0%*** 55.8%*** 0% weeks be able 1: summary of key results • in this phase 2b, double-blind, placebo-controlled study (nct02905006), patients with moderate-to-severe plaque psoriasis were randomized (1:1:1:1:1:1) to receive bimekizumab 64 mg, 160 mg, 160 mg with 320 mg loading dose, 320 mg, 480 mg, or placebo every 4 weeks for 12 weeks; the primary objective was to evaluate the dose response of bimekizumab7 • there was a significant dose response for psoriasis area severity index (pasi)90 (p<0.0001) at week 12. the primary endpoint, pasi90 at week 12, was achieved by significantly more patients receiving each bimekizumab dose compared with placebo (figure 2a)7 • up to 60.0% of bimekizumab-treated patients achieved complete skin clearance (pasi100) at week 12 (figure 2b)7 • the safety profile of bimekizumab was consistent with previous studies4,5 with no unexpected safety findings7 figure 2a. pasi90 response over time7; figure 2b. pasi100 response over time7, full analysis set (nonresponder imputation); **p<0.001, ***p<0.0001 versus placebo (fisher’s exact test); note: no patients receiving placebo achieved pasi90 or pasi100 at any time point; se, standard error methods • patients completed the dermatology life quality index (dlqi) questionnaire at baseline, week 1, week 2, week 4, week 8 and week 12 • dlqi of 0 or 1 was used to indicate no impact of psoriasis on disease-specific hrqol; minimal clinically important difference (mcid) was defined as 4-point reduction in dlqi from baseline • patients were grouped by absolute pasi (≤1, >1–≤2, >2–≤5, >5) and bsa affected by psoriasis (≤1%; >1–≤3%, >3–≤5%, >5%) to evaluate a possible correlation between clinical response and achievement of dlqi 0 or 1 • patient demographics and baseline disease characteristics were balanced across treatment groups (mean [sd] dlqi total: 10.7 [6.9]; pasi: 19.1 [6.5]; percentage bsa involvement: 25.1 [13.3])7 0 20 40 60 80 100 0 2 4 6 8 10 12 weeks 0% 46.2%*** 67.4%*** 72.1%*** 75.0%*** 79.1%*** p a s i9 0 re sp on se , % ( s e ) of p at ie nt s pasi90 response pasi100 response 27.3 81.3 90.9 100 97.1 96.4 10.5 66.7 76.5 78.6 53.3 85.7 7.7 53.8 37.5 80.0 57.1 62.5 0 20 40 60 80 100 placebo bkz 64 mg bkz 160 mg bkz 160 mg (320 mg ld) bkz 320 mg bkz 480 mg a) b) 3x mcid n=19 4x mcid n=13 mcid n=33 3x mcid n=21 4x mcid n=13 mcid n=32 3x mcid n=17 4x mcid n=8 mcid n=33 3x mcid n=14 4x mcid n=10 mcid n=29 3x mcid n=15 4x mcid n=7 mcid n=35 3x mcid n=14 4x mcid n=8 mcid n=28 placebo; n=36 m c id in d lq i, % p at ie nt s* objective to evaluate disease-specific health-related qualify of life (hrqol) data from the phase 2b study7 and its correlation with the absolute pasi and body surface area (bsa) affected figure 3. absolute pasi and dlqi over time (patient-level data); x missing data imputed as last observation carried forward; box plots are first quartile, median and third quartile. whiskers extend to ±1.5 times the interquartile range. where the whisker value exceeded the data range, the maximum or minimum value was used, as appropriate placebo; n=42 bkz 64 mg; n=39 bkz 160 mg; n=43 bkz 320 mg; n=43 bkz 160 mg (320 mg ld at baseline); n=40 bkz 480 mg; n=43 pasi placebo; (n = 42) bkz 480 mg; (n = 43) bkz 320 mg; (n = 43) bkz 160 mg; (n = 43) bkz 64 mg; (n = 39) bkz 160 mg; (320 mg ld; n = 40) 0 5 10 15 20 25 30 35 40 45 50 p a s i baseline week 4 week 8 week 12 pasi=2 slide number 1 skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 1 editorials should package insert warnings deter prescribing in psoriasis patients with depression? graham h litchman do, ms,1 quinn thibodeaux, md,2 ryan rivera-oyola, ms,3 john koo, md,2 rick fried, md, phd,4 gary goldenberg, md,3,5 george han, md,3 sylvia hsu, md,6 leon kircik, md,3,7 melissa knuckles, md,8 andrea murina, md,9 jeffrey weinberg, md,4 jashin j. wu,md,10 mark lebwohl, md3 1st. john’s episcopal hospital, department of dermatology, far rockaway, ny 2university of california san francisco, department of dermatology, san francisco, ca. 3icahn school of medicine at mt sinai hospital, department of dermatology, new york, ny 4yardley dermatology associates; yardley clinical research associates, morrisville, pa 5goldenberg dermatology, new york, ny 6temple university lewis katz school of medicine, department of dermatology, philadelphia, pa 7indiana university medical center, indianapolis, in 8m.l.f. knuckles dermatology, corbin, ky; m.l.f. knuckles dermatology richmond, ky; adventhealth hospital, manchester, ky 9tulane university school of medicine, department of dermatology, new orleans, la 10dermatology research and education foundation, irvine, ca abstract introduction: psoriasis, an immune-mediated disease that manifests cutaneously with possible arthritic complications, affects millions of people in the united states and worldwide. depression and suicidal ideation and behavior (sib) are two prevalent comorbidities associated with psoriasis, due to the chronic nature of the disease, lack of a cure, as well as social stigma, all of which are detrimental to quality of life. among the options available for management of moderate-severe psoriasis, apremilast and brodalumab represent recent additions to the therapeutic armamentarium for managing psoriasis. it has been suggested that the aforementioned drugs can lead to depression and possibly increase the risk for sib. furthermore, a black box warning was issued for brodalumab. this review challenges opinions that the drugs are solely responsible for exacerbating depression and sib, when in fact it could be psoriasis itself. methods: an extensive search of available literature linking cytokines to suicidal behavior was performed. after filtering for relevance, 22 articles were reviewed in detail. results: brodalumab and apremilast, both molecularly and clinically, do not objectively increase the risk for depression and/or suicidal ideation and behavior. conclusion: after careful review of the appropriate studies and relevant literature, patients with moderate-severe psoriasis, including those that experience depression resulting from their chronic condition, would likely benefit from early, rather than delayed initiation of effective medications like apremilast and brodalumab. the speed of response and high level of efficacy of brodalumab make it an ideal intervention for patients suffering depression caused by their psoriasis. skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 2 psoriasis, an immune-mediated disease that manifests as itchy, red scaling plaques along with possible arthritic complications, affects 8 million people in the united states, and upwards of 3% of the worldwide population.1 depression and suicidal ideation and behavior (sib) are two prevalent comorbidities associated with psoriasis due to the chronic nature of the disease, lack of a cure, as well as the social stigma, all of which are detrimental to quality of life. among the options available for management of moderate-severe psoriasis, apremilast, which targets phosphodiesterase-4 (pde4), and brodalumab, which targets interleukin-17 (il17) receptor a, represent recent additions to our therapeutic armamentarium for managing psoriasis. brodalumab has a faster onset when compared to other monoclonal antibodies indicated for psoriasis.2 this faster onset is important, in terms of more efficiently decreasing disease burden and alleviating treatment dissatisfaction, a problem that has plagued older treatment options.3 this review challenges opinions that the drugs are solely responsible for exacerbating depression and sib, when in fact it could be psoriasis itself, whether untreated or unresponsive to prior treatment, that may contribute to diminished quality of life and depression. in fact, it is successful and, more importantly, timely control of psoriatic symptoms that often improves psychological comorbidity outcomes. furthermore, package insert warnings may discourage clinicians from prescribing needed medication and introduce unnecessary additional psychological burden to patients, which is counterproductive to maintaining long-term wellbeing. these concerns may be further accentuated for medications that are issued black box warnings (such as brodalumab).4 instead, thorough screening and referral of patients who display signs of depression or sib eschews the need for black box warnings. such warnings indicate an enhanced level of danger while using the drug which is, in this case, unnecessary. cytokines and depressive/suicidal behavior a search of available literature linking cytokines to suicidal behavior implicate elevated il-6 levels likely having an association with increases in suicidal ideation.5 for il-17 specific studies, all point to elevated levels of il-17a as contributing to higher depressive symptoms;6-8 both apremilast and brodalumab contribute to decreasing il-17 expression, or inhibition of il-17 binding to its receptor, respectively, and consequently would be expected to reverse depression and sib. similarly, other reports suggest that specifically targeting pro-inflammatory cytokines will likely decrease and treat depressive symptoms.9 apremilast apremilast, an orally administered phthalimide-based small molecule, is a pde4 inhibitor that prevents the hydrolysis of cyclic adenosine monophosphate (camp).this inhibition causes several proinflammatory cytokines, such as il-17, il23, and tumor necrosis factor alpha (tnfa) to be down-regulated, while at the same time upregulating il-10, an antiinflammatory factor.10 it was approved in 2014 to treat psoriatic arthritis and plaque psoriasis. introduction results skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 3 due to its low molecular weight (460 da), it could theoretically cross the blood-brain barrier (bbb) and potentially affect brain chemistry and patient mood. however, tissue distribution studies using 14c-labeled drug consistently showed low concentrations of apremilast within the cns, indicating poor penetration of the blood-brain barrier.11 the highest levels of radioactivity were observed in organs involved with metabolism and subsequent clearance (liver, kidneys).11 two phase iii trials(esteem 1 – 2; palace 1 – 3) were carried out to study long-term efficacy and tolerability of apremilast (≥ 3 years for esteem, up to five years for palace). for the populations of both esteem trials12 (n = 1250), 178 (14.2%) patients reported a history of depression, while 156 (12.4%) were taking an antidepressant. there was one suicide attempt in the treatment arm (0 to ≤ 52 weeks), and one completed suicide in the placebo arm during esteem 1. the incidence of depression did not increase with extended apremilast use and there were no other reports of suicide. more importantly, the rate of depression in the esteem trials were lower than the background rate in the psoriasis population (≥10%), when compared to reported values.13,14 across palace 1 – 3 (n = 1493),15 reports of depression remained low, with a slightly higher incidence in the treatment arm (1.2%) compared to the placebo arm (0.8%). there were no completed suicides in the experimental arm during the study, and two reported attempts: one during the 0 to ≤ 52 weeks exposure period to apremilast, and one during the > 52 to ≤ 104 weeks of exposure. both attempts were attributable to external risk factors (serious family altercation in the former case, and a history of depression, affective disorder, and physical/emotional abuse in the latter). there were, however, two completed suicides in the placebo arm. brodalumab brodalumab is a humanized monoclonal antibody, approved in 2017 to treat severe plaque psoriasis, in particular for patients who have not responded to or have low tolerability for other systemic therapy.16 it binds directly to the il-17 receptor a, preventing activation by il-17a, il-17f, il17a/f, il-17c, and il-17e (il-25); this is in contrast to other monoclonal antibodies such as ixekizumab, which only binds to il17a.17 brodalumab, being a whole antibody (144 kda), is too large, and too hydrophilic, for successful penetration of the bbb; by comparison, the largest known protein able to cross the blood-brain barrier via transmembrane diffusion is cytokine-induced neutrophil chemoattractant (cinc-1), at 7.8 kda.18 saturable transport systems, whether efflux or influx, primarily have small molecule substrates, such as glucose, amino acids, and signaling molecules such as epinephrine.19 there were three phase iii trials for brodalumab (amagine 1 – 3; n = 4373) to assess efficacy and safety, monitored at up to 52 weeks. several clinical assessments were used to ascertain patient response, including hospital anxiety and depression scale (hads), psoriasis area and severity index (pasi), psoriasis symptom inventory (psi), and static physician’s global assessment (spga). in amagine-1,20 pooled population data (n = 220 for placebo, n = 441 for treatment) indicated substantial improvement of psoriasis symptoms at 12 weeks exposure: 317 patients had achieved at least pasi 75, skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 4 compared to 6 in placebo. of those 317, 249 had pasi 90, and 144 had pasi 100. improvement was also seen in their hads scores: baseline mean scores for the 140 mg treatment arm saw a reduction in depression scores from 5.2 ± 4.1 to 3.6 ± 0.3 after 12 weeks, while the 210 mg treatment arm saw a similar reduction from 5.5 ± 4.2 at baseline, to 3.5 ± 0.2 after 12 weeks. through week 52 in amagine-1, there was one completed suicide by hanging. in amagine 2-3, there were two additional completed suicides.4 in addition to the three completed suicides mentioned above, one (secondary to a drug overdose with opiates and alcohol) was subsequently ruled indeterminate by the columbia classification algorithm for suicide assessment (c-casa). for the remaining three, all had received 210 mg doses of brodalumab, and had pasi scores of 73, 100, and 100; however, none of the suicides occurred within three months of treatment initiation (140, 329, and 845 days after first dose, respectively). in addition, similar to the suicide observed in the palace trials for apremilast, the three patients had external factors unrelated to brodalumab treatment, including financial stressors, the possibility of incarceration due to legal difficulties, and ongoing treatment for depression and anxiety.4 from a molecular perspective, both apremilast and brodalumab are unable to effectively penetrate the blood-brain barrier. the inhibition of il-17 receptors or il-17 and related isoforms, based on previous studies, would imply that reducing the effects of il17 would help in decreasing depression and suicidal ideation and behavior. clinically, the instances of suicide attempts and completed suicides reported in phase iii trials for apremilast (esteem and palace) and brodalumab (amagine) are confounded by external factors that are unrelated to drug or biologic administration. as previously stated, none of the three completed suicides in the brodalumab psoriasis trials occurred within three months of treatment initiation, the period in which the majority of patients showed substantial improvement in controlling psoriasis symptoms, as shown by statistically significant improvement in hads and pasi scores after 12 weeks. reports of depression for the duration of each clinical trial are also below population averages of psoriasis patients when previous data and meta-analyses are considered. many factors should be considered when selecting the optimal therapy for patients with psoriasis.21,22 after careful review of the appropriate studies and relevant literature, patients with moderate-severe psoriasis, including those that experience depression resulting from their chronic condition, would likely benefit from early, rather than delayed initiation of effective medications like apremilast and brodalumab. the speed of response and high level of efficacy of brodalumab make it an ideal intervention for patients suffering depression caused by their psoriasis. conflict of interest disclosures: ghl, qt, rro have no relevant conflicts of interest. jk is a speaker and advisor for abbvie, amgen, celgene, janssen, eli-lilly, leo pharma, novartis, pfizer, strata skin science, sun pharma, and orthodermatologic. rf has no relevant conflicts of interest. gg is a consultant and speaker for abbvie, amla, bayer, celgene, dermira, leo, novartis, pharmaderm, pfizer, and regeneron/sanofi. he is a consultant for allergan, amgen, almirall, castle, eclipse, galderma, genentech, gsk/stiefel, intraderm, isdin, janssen, menlo, ranbaxy, scibase, suneva, teva, valeant/ortho discussion conclusion skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 5 dermatologic, and verrica. he is a speaker for merz and on the board of directors of verrica. gh is an advisor, speaker and consultant for janssen, orthodermatologic, regeneron/sanofi, eli lily, ucb, abbvie, sun pharma, and pfizer. he is an investigator for pfizer, novartis, eli lily, janssen, mc2 therapeutics, bond avillion, celgene, and athenex. sh has been an investigator for celgene and novartis and an advisor for janssen, ortho dermatologics, and menlo therapeutics. lk is a speaker for abbott laboratories, allergan, amgen, assos pharma, astellas pharma us, inc., cipher, collagenex, connetics corporation, dermik laboratories, embil pharmaceuticals, exeltis, genentech, innocutis, innovail, johnson & johnson, leo, l’oreal, 3m, onset, orthoneutrogena, pediapharm, pharmaderm, serono, skinmedica, stiefel laboratories, sun pharma, taro, triax, ucb, valeant pharmaceuticals, and warner-chilcott. he has participated in advisory boards for aclaris, allergan, almirall, anacor, biogen-idec, colbar, celgene, cipher, connetics, eos, exeltis, ferndale laboratories, genentech, intendis, innocutis, isdin, johnson & johnson, merz, orthoneutrogena, promius, quinnova, skinmedica, stiefel laboratories, sun pharma, valeant, and warner-chilcott. he is an investigator for acambis, allergan, amgen, anacor, astellas, asubio, berlex, biolife, biopelle, boehringeringleheim, breckinridge pharma, celgene, centocor, cellceutix, coherus, collagenex, combinatrix, connetics corporation, coria, dermavant, dermira, dow pharmaceutical sciences, dusa, eli lilly, exeltis, ferdale laboratories, foamix, genentech, glaxosmithkline, health point, idera, intendis, johnson & johnson, leo, l’oreal, 3m, maruho, merck, medicis, merz, novartis, noven, nucryst, obagi, onset, orthoneutrogena, promius, qlt, pharmaderm, pfizer, quinnova, quatrix, skinmedica, stiefel, sun pharma, tolerrx, ucb, valeant, warner-chilcott, and xenoport. he is a consultant for allergan, almirall, amgen, anacor, colbar, cipher, collagenex, connetics, exeltis, genentech, intendis, isdin, johnson & johnson, laboratory skin care, leo, medical international technologies, merck, merz, novartis, orthoneutrogena, promius, puracap, skinmedica, stiefel, sun pharma, taro, ucb, valeant, and zage. mk is a speaker for siliq, cosentyx, otezla, eucrisa, ilumya, cimzia, sunpharma, novartis, celgene, abbvie, amgen, duobrii, bryhali, dupixent, enbrel, amgen, abbvie, humira, skyrizi. she is on advisory boards for promius, siliq, ortho dermatologics, corrona investigator, castle bioscience, novartis, sanofiregeneron, and ilumya. am is a speaker for abbvie, amgen, eli lilly and company, janssen, and novartis. she has participated in advisory boards for ortho dermatologics and janssen. jw is a speaker and investigator for celgene and a speaker for orthodermatologic. jjw is or has been an investigator, consultant, or speaker for abbvie, almirall, amgen, boehringer ingelheim, bristol-myers squibb, celgene, dermavant, dermira, dr. reddy's laboratories, eli lilly, janssen, leo pharma, novartis, regeneron, sanofi genzyme, sun pharmaceutical, ucb, valeant pharmaceuticals north america llc. ml is an employee of mount sinai and receives research funds from: abbvie, amgen, arcutis, astrazeneca, boehringer ingelheim, celgene, clinuvel, eli lilly, incyte, janssen research & development, llc, kadmon corp., llc, leo pharmaceutucals, medimmune, novartis, ortho dermatologics, pfizer, sciderm, ucb, inc., and vidac, and is also a consultant for allergan, almirall, arcutis, inc., avotres therapeutics, birchbiomed inc., boehringer-ingelheim, bristol-myers squibb, cara therapeutics, castle biosciences, corrona, dermavant sciences, evelo, foundation for research and education in dermatology, inozyme pharma, leo pharma, meiji seika pharma, menlo, mitsubishi, neuroderm, pfizer, promius/dr. reddy’s laboratories, theravance, and verrica. funding: none corresponding author: graham h. litchman, do, ms department of dermatology st. john’s episcopal hospital far rockaway, ny phone: 203-940-0373 email: graham.litchman@gmail.com references: 1. parisi r, symmons dp, griffiths ce, ashcroft dm; identification and management of psoriasis and associated comobidity (impact) project team. global epidemiology of psoriasis: a systematic review of incidence and prevalence. j invest dermatol. 2013 feb;133(2):377-85. 2. foulkes ac, warren rb. brodalumab in psoriasis: evidence to date and clinical potential. drugs context. 2019 apr 17;8:212570. 3. stern rs, nijsten t, feldman sr, margolis dj, rolstad t. psoriasis is common, carries a substantial burden even when not extensive, and is associated with widespread treatment dissatisfaction. j. investig. dermatol. sympos. proc. 2004 mar;9(2):136-139. 4. lebwohl, mg, papp ka, marangell lb, koo j, blauvelt a, gooderham m, wu jj, rastogi s, skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 6 harris s, pillai r, israel rj. psychiatric adverse events during treatment with brodalumab: analysis of psoriasis clinical trials. j am acad dermatol. 2018 jan;78(1): 81-89. 5. ganança l, ouquendo ma, tyrka ar, cisnerostrujillo s, mann jj, sublette me. the role of cytokines in the pathophysiology of suicidal behavior. psychoneuroendocrinology. 2016;63:296-310. 6. davami mh, baharlou r, ahmadi vasmehjani a, ghanizadeh a, keshtkar m, dezkham j, atashzar mr. elevated il-17 and tgf serum levels: a positive correlation between t-helper 17 cell-related pro-inflammatory responses with major depressive disorder. basi clin. neurosci. 2016 apr;7(2):137-142. 7. nadeem a, ahmad sf, al-harbi no, fardan as, el-sherbeeny am, ibrahim ke, attia sm. il-17a causes depression-like symptoms via nf b and p38mapk signaling pathways in mice: implications for psoriasis associated depression. cytokine. 2017 sept;97:14-24. 8. tsuboi h, sakakibara h, minamida y, tsujiguchi h, matsunaga m, hara a, nakamura h. elevated levels of serum il-17a in community-dwelling women with higher depressive sumptoms. behav. sci. (basel). 2018 nov;8(11):102-108. 9. raison cl, capuron l, miller ah. cytokines sing the blues: inflammation and the pathogenesis of depression. trends immunol. 2006 jan;27(1):2431. 10. schafer p. apremilast mechanism of action and application to psoriasis and psoriatic arthritis. biochem. pharmacol. 2012;(83(12):1583-1590. 11. european medicines agency. (2014). assessment report: otezla. retrieved from https://www.ema.europa.eu/en/documents/asses sment-report/otezla-epar-public-assessmentreport_en.pdf. 12. crowley j, thaçi d, joly p, peris k. et al. longterm safety and tolerability of apremilast in patients with psoriasis: pooled safety analysis for ≥ 156 weeks from 2 phase 3, randomized, controlled trials (esteem 1 and 2). j am acad dermatol. 2017;77(2):310-317. 13. gooderham m, papp k. selective phosphodiesterase inhibitors for psoriasis, focus on apremilast. biodrugs. 2015;29(5):327-339. 14. dowlayshahi ea, wakkee m, arends lr, nijsten t. the prevalence and odds of depressive symptoms and clinical depression in psoriasis patients: a systematic review and meta-analysis. j invest dermatol. 2014;134(6):1542-1551. 15. kavanaugh a, gladman dd, edwards cj, schett g, guerette b, delev n, teng l, paris m, mease pj. long-term experience with apremilast in patients with psoriatic arthritis: 5-year results from a palace 1-3 pooled analysis. arthritis res. ther. 2019;21(118). 16. menter a, strober be, kaplan dh, kivelevitch d et al. joint aad-npf guidelines of care for the management and treatment of psoriasis with biologics. j. amer. acad. dermatol. 2019 apr;80(4):1029-1072. 17. european medicines agency. (2016). assessment report: taltz. retrieved from https://www.ema.europa.eu/en/documents/asses sment-report/taltz-epar-public-assessmentreport_en.pdf. 18. pan w, kastin, aj. changing the chemokine gradient: cinc1 crosses the blood-brain barrier. j. neuroimmunol. 2011;115(1-2):64-70. 19. banks wa. characteristics of compounds that cross the blood-brain barrier. bmc neurology. 2009;9(suppl. 1):s3. 20. papp ka, reich k, paul c, blauvelt a, baran w, bolduc c, toth d, langley rg, cather j, gottlieb ab, thaçi d, kreuger jg, russell cb, milmont ce, li j, klekotka pa, kricorian g, nirula a. a prospective phase iii, randomized, double-blind, placebo-controlled study brodalumab in patients with moderate-to-severe plaque psoriasis. br j dermatol. 2016 aug;175(2):273-286. 21. kaushik sb, lebwohl mg. psoriasis: which therapy for which patient: 22. psoriasis comorbidities and preferred systemic agents. j am acad dermatol. 2019;80(1):27-40. 23. kaushik sb, lebwohl mg. psoriasis: which therapy for which patient. focus on special populations and chronic infections. j am acad dermatol. 2019;80(1):43-53. about:blank about:blank about:blank microsoft word may 2021 idr 1239 proof.docx skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 203 in-depth review apremilast as an off-label therapeutic agent: a comprehensive review of safety and efficacy data in the literature for combination therapy and inflammatory dermatoses justin w. marson, md1, mark g. lebwohl, md2 1suny downstate health sciences university, brooklyn, ny 2department of dermatology, icahn school of medicine at mount sinai, new york, ny apremilast is an oral, small molecule phosphodiesterase 4 (pde4) inhibitor that was originally us food and drug administration (fda) approved for the management of psoriatic arthritis and chronic plaque psoriasis in 2014.1 by inhibiting the degradation of cyclic adenosine monophosphate (camp), apremilast modulates the activity of multiple immune cell lines including macrophages, neutrophils and natural killer cells within the th1 and th17 pathways as well as myriads of pro-inflammatory cytokines including tumor necrosis factor alpha (tnf-α), interleukin 12 (il-12) and il-23 as well as anti-inflammatory cytokines such as il-10.2,3 clinically, this has translated into successful, abstract objective: to review the literature regarding the efficacy and safety of off-label use of apremilast in combination therapies for psoriasis and psoriatic arthritis and for other currently off-label inflammatory dermatoses. methods: the medline database was queried for all relevant articles published between 2014 and 2021 using exploded mesh terms and keywords pertaining to the following themes: off-label, combination therapy, biologics, biologic therapy, methotrexate, and systemic psoriasis therapy. the boolean term “and” was used to find the intersection of these themes with the term “apremilast.” results: 8 case series and 6 case reports investigated the use of apremilast in combination therapy for psoriasis and psoriatic arthritis. addition of apremilast improved pasi scores by 31.8-77.4% among case series and 80-100% among case reports with adverse effects primarily consisting of gastrointestinal symptoms. 5 randomized-control trials (rct), 9 open-label trials, 18 case series, and 30 case reports investigated the use of apremilast for off-label dermatoses. in rcts, apremilast showed potential efficacy for atopic dermatitis and hidradenitis suppurativa. open-label trials found apremilast efficacious for atopic dermatitis, allergic contact dermatitis, chronic pruritus, cutaneous sarcoidosis, discoid lupus erythematosus, hidradenitis suppurativa, lichen planus, prurigo nodularis, rosacea, and vitiligo. limitations: small sample size and short follow up duration for available randomized-control and openlabel trials. current data from case series/reports potentially limits generalizability of findings. conclusion: apremilast's safety profile makes it a potential efficacious, non-biologic systemic agent for monotherapy and combination therapy for a wide range of inflammatory dermatoses. introduction skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 204 non-biologic oral therapy for patients with psoriasis and psoriatic arthritis with first signs of meaningful response notable within 2 weeks.4-6 the efficacy of apremilast is complemented by its safety profile.7 clinical trials have shown that the most common treatmentemergent adverse events (teae) are gastrointestinal related (diarrhea, nausea), weight loss, upper respiratory tract infections and that apremilast does not increase risk of malignancy or opportunistic infections.7 furthermore, post-marketing surveillance as well as clinical and pharmacological data have not supported (if not refuted) correlation between depression and apremilast.8,9 because apremilast is an oral, non-biologic systemic agent with a favorable safety profile, there has been growing interest in its application for other off-label use in either combination therapy for fda-approved conditions or for other inflammatory dermatoses. this growing interest in expanding indication earned apremilast fda-approval in 2019 for use in behçet’s syndrome in 2019.1,10 additional studies have also investigated the off-label use of apremilast in conjunction with other therapies, including biologics and methotrexate for more recalcitrant cases of psoriasis or psoriatic arthritis.6,11-13 the purpose of this study is to review the literature for off-label uses of apremilast with respect to other inflammatory conditions as well as combination therapies. a review of the literature pertaining to offlabel use of apremilast as well as combination therapies was conducted. the medline database was queried for all relevant articles published between 2014 and 2021 using exploded mesh terms and keywords pertaining to the following themes: off-label, biologics, methotrexate, and systemic psoriasis therapy. the boolean term “and” was used to find the intersection of these themes with the term “apremilast.” studies were limited to english-only manuscripts with available full-text. details regarding study design (case reports, caseseries, open-label trial or randomized controlled trials (rcts)), outcomes, followup duration, and treatment-emergent adverse events (teae) were abstracted. combination therapy for psoriasis and psoriatic arthritis the advances in understanding psoriasis as a systemic inflammatory condition fostered the development of immunomodulating targeted biologic agents, many of which are able to reach 100% improvement as captured by the psoriasis activity and severity index (pasi100).14,15 however, longitudinal studies have demonstrated a decrease in efficacy of certain biologic agents over time.15-18 this secondary failure or biologic fatigue can be observed in up to 20-30% of patients as little as 1-4 years after initially reaching pasi75, potentially due to the creation of neutralizing anti-drug antibodies leading to subtherapeutic serum drug levels.15-17 while switching biologics can recapture efficacy, these effects may not be durable and are also dependent on the selected drug and drug class.18 alternatively, studies have also investigated combining different drug classes and mechanisms of action with durable and efficacious results.13,19-31 several case series and reports found patients who experienced secondary failure while on a methods results skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 205 biologic or other non-biologic systemic agents (e.g. methotrexate) obtained pasi50-100 throughout a follow up period of 3-9 months with similar treatment-emergent adverse effects [teae] to monotherapy (table1).13,19-25,26-31 collectively several case studies have noted that the addition of apremilast to either systemic biologic or nonbiologic therapies had a mean additional improvement in pasi scores between 31.877.4% for patients that were either unsatisfied with their current regimen or experienced secondary failure.13,19,21,22 while additional efficacy varied depending on the pre-apremilast regimen, most patients saw durable results with a range of means between 12 and 31 weeks.13,19-25 several studies also found additional benefit in combining narrow-band uvb (nbuvb) phototherapy with apremilast, with additional improvements in pasi of 76.4-81.5%.13,25 furthermore, none of these therapeutic combinations resulted in severe infections in the management of psoriasis or psoriatic arthritis. only one study noted 3 upper respiratory tract infections over 16 weeks.22 in one study, 14 patients opted to discontinue apremilast prior to the 12-week follow-up due to “intolerable” gastrointestinal symptoms (n = 9), headache (n = 1), a transient urticarial rash (n = 1) and 2 due to patient preference.28 overall, 20-25% of patients experienced self-limited diarrhea, nausea, and weight loss. depression or depressive symptoms were not noted in patients on any combination therapy with apremilast.18-25 several studies compared apremilast monotherapy to combination therapy with apremilast and found no significant difference in the rate of treatmentemergent adverse effects (teae).22,23 several case reports also found utility of apremilast in combination therapies, especially in more recalcitrant cases of psoriasis, which had failed multiple topical and systemic agents.26-31 in 5 out of the 6 cases, patients saw additional significant reduction in the severity of their psoriasis with the addition of apremilast to their systemic agent, with only 1 instance of mild diarrhea.26,28-31 one report further detailed improvement in both psoriasis and psoriatic arthritis with the sequential initiation of apremilast 30 mg bid and secukinumab 300 mg monthly with achieved pasi100 and reduced eight tender and seven swollen joints to 2 tender and no swollen joints in 16 weeks.31 only 1 case, in which the patient had a rare hla-c*18:01 mutation causing multiple-regimen resistant, recalcitrant psoriasis, did not see improvement with the addition of apremilast to ustekinumab.27 together these data demonstrate a pattern of efficacy and safety when apremilast is added or included in combination therapy, especially for patients with a history of recalcitrant psoriasis. randomized-control and open-label trials investigating off-label apremilast use apremilast’s unique combination of safety profile and multifaceted mechanism of action have sparked interest into potential uses in other inflammatory dermatoses. as a result, several randomized-control trials (rct), open-label trials, case reports, and case series have investigated, with varying degrees of success, how apremilast may fit into the therapeutic framework for conditions including (but not limited to) other papulosquamous, vesiculobullous, granulomatous dermatoses, connective tissue, and pigmentary disorders (table 35).32-96 alopecia areata a randomized control trial of patients with long standing moderate to severe alopecia areata (aa) (>50% involvement of the scalp) skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 206 table 1. case series of combination therapies including apremilast for psoriasis and psoriatic arthritis study mean age (sd) sex m/f add’l pso subtype combination regimen (n) follow-up period weeks, mean (sd) mean %pasi* improvement (sd) teae† (n) diar naus wt infxn abuhilal et al.13 48.8 47.3 37.7 52.6 52.4 53.2 53.4 7/3 5/10 1/3 4/1 5/8 5/2 6/7 - +nbuvb (10) +methotrexate (15) +cyclosporine (4) +acitretin (5) +tnf-inhibitor (13) +tnf-inhibitor & methotrexate (7) +ustekinumab (13) 12 (0) 81.5 67.8 63.3 76.5 70.4 76.8 77.4 4 4 1 2 3 2 4 1 2 1 1 2 1 2 - - - - - - - - - - - - - - takamura et al.19 51.4 (2.4) 14/0 - 2 psa - - 1 psa +infliximab (1) +adalimumab (3) +secukinumab (2) +ixekizumab (2) +ustekinumab (6) 24 (0) 77 31.8 (32.1) 35.7 (22.2) 39.6 (10.3) 67.2 (30.0) - 1 1 1 2 - - - 1 - - 2‡ - - - - - - - - metyas et al.20 --22 psa +adalimumab (6) +infliximab (4) +golimumab (3) +certolizumab pegol (2) +etantercept (2) +ustekinumab (5) r: 12-42 r:4-68 r:12-44 r:4-36 r:4-28 r:16-106 -2 2 1 - saccheli et al.21 48.25 (10.9) 1/3 2 psa +secukinumab (4) 31 (5.03) 75.4 (20.7) yes --- ighani et al.22 51.5 (11.9) 51/38 51 psa +phototherapy (2) +cyclosporine (3) +methotrexate (19) +sulfasalazine (2) +etanercept (18) +adalimumab & methotrexate (8) +infliximab (7) +adalimumab (5) +secukinumab (3) +ustekinumab (14) +ustekinumab & acitretin (3) +infliximab & methotrexate (2) 16 (0) 51.3 15 10 9 uri (4) abignano et al.23 51.5 (2) 17/15 32 psa 26 pso +methotrexate (16) +sulfasalazine (1) 22.9 (13.5) -5 2 -- skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 207 +hydroxychloroquine (2) +leflunomide (1) +certolizumab (1) +golimumab (2) +ustekinumab (1) +adalimumab (1) +etanercept (1 +secukinumab (1 +tocilizumab (1) +methotrexate & sulfasalazine (1) +methotrexate & hydroxychloroquine (1) +methotrexate & certolizumab (1) +methotrexate & ustekinumab (1) wald et al. 24 ---+methotrexate (1) 11.4 (0) --yes -- bagel et al.25 47 (11) 17/12 -+nbuvb (29) 12 (0) 76.4 -2 -- -indicates specific data not provided *%pasi improvement after addition of apremilast to current regimen, †not mutually exclusive unless otherwise noted, ‡>5% original body weight diar – diarrhea; f – female; infxn – infection; m – male; naus – nausea; pasi – psoriasis area and severity index; psa – psoriatic arthritis; pso – psoriasis; r – range; sd – standard deviation; teae – treatment-emergent adverse events; wt – weight loss skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 208 table 2. case reports of combination therapy using apremilast 30 mg twice daily/60 mg daily for psoriasis and psoriatic arthritis study age sex pso subtype prior regimens combination regimen followup (wks) %pasi improvement teae d/c tx? czarnowic ki et al.26 50 m ppp topical steroids, tacrolimus, excimer laser, acitretin +acitretin (25mg/d) 8 90 -no armesto et al.27 28 f erythroderma pso methotrexate, cyclosporine, infliximab, adalimumab, etanercept, ustekinumab, secukinumab, golimumab, certolizumab, apremilast monotherapy +adalimumab (40mg/wk) & methotrexate (10mg/wk) & prednisone taper (20mg/day) +brodalumab (210mg/wk) & methotrexate (20mg/wk) & prednisone (30 mg/day) 4 36 - 86 - - worsening prompted change of biologic galluzzo et al.28 63 m pso, hla-c*18:01 infliximab, etanercept, ustekinumab, adalimumab, infliximab re-trial, ustekinumab re-trial, secukinumab +ustekinumab (45 mg) 12 --† - worsening condition rothstein et al.29 67 m pso, psa ustekinumab, infliximab, adalimumab, acitretin, cyclosporine, secukinumab, +secukinumab (300mg/month) 12 80% bsa to 5%† mild diarrhea no danesh et al.30 31 m pso topical steroids, nbuvb, acitretin, etanercept, adalimumab +adalimumab (40mg/qow) 16 improved† -no nisar31 23 m pso, psa cyclosporine, sulfasalazine, methotrexate, adalimumab, ustekinumab, infliximab +secukinumab (300mg/month) 16 100 & psarc 8 tender/7 swollen joints to 2 tender/0 swollen -no †pasi scores not available %pasi – percent improvement in psoriasis area and severity index after addition of apremilast to current regimen; d/c tx– discontinued therapy; f – female; m – male; ppp – palmarplantar psoriasis; psa – psoriatic arthritis; psarc – psoriatic arthritis response criteria; pso – plaque psoriasis; qow – every other week; teae – treatment-emergent adverse effects; wks – weeks skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 209 found that apremilast 20 mg bid over 24 weeks was not superior to placebo in achieving 50% reduction in severity of alopecia tool (salt50) score.32 the authors note that this may be due to the severity and chronicity of disease in study participants, small sample size, and short duration of the study.32 several case series and reports have found more positive results with 4087% of participants experiencing sustained regrowth of scalp hair and eyelashes.33-37,43 of note, authors of these studies found patients with more refractory cases were less likely to respond to apremilast monotherapy. teae consisted mostly of gastrointestinal distress (nausea, diarrhea) which was transient or tolerable with dose decrease33. in rare instances, persistent arthralgias, nausea and/or diarrhea led to premature discontinuation of apremilast.32 atopic dermatitis, chronic pruritus, prurigo nodularis, hand eczema, and allergic contact dermatitis mixed results have been found regarding apremilast’s use in ad, similar eczematous disorders in the atopic spectrum of disorders (e.g., chronic pruritus, prurigo nodularis, hand eczema) and allergic contact dermatitis (acd). a phase ii rct found that apremilast 30 mg bid trended towards improvement, though did not significantly improve atopic dermatitis than placebo.38 when the dose was increased to 40 mg bid, there was a significant improvement in eczema area and severity index (easi) score and dermatology life quality index (dlqi) as well as improvement in biochemical markers of ad.38 however, the increased dose also led to increased incidence of cellulitis (n=6) which ultimately lead to termination of this arm of the study.38 2 of the 6 cases of cellulitis were deemed serious and occurred in patients with diabetes; one of those cases may have also been associated with an observed case of glomerulonephritis.38 open-label trial results have also yielded conflicting conclusions. an open-label trial with a 20 mg bid (n=6) and 30 mg bid (n = 10) arm found that they were both significantly effective in improving pruritus (20 mg bid; p=.02; 30 mg bid, p=.008) as well as quality of life (20 mg bid, p = .003; 30 mg bid, p = .01) among participants within 12 weeks and that 30 mg bid yielded significantly improved easi score at 24 weeks.39 1 patient in the 20 mg arm withdrew from the study after experiencing an outbreak of herpes zoster.39 a smaller open-label trial of 5 participants found a 20% worsening of easi scores over 16 weeks, leading to drug withdrawal of 4 participants (2 due to worsening ad and 2 due to nonadherence).40 interestingly the authors of this trial noted the patients with atopic dermatitis had a worse easi score at the outset.40 case series and reports have shown that, for atopic dermatitis patients that responded to apremilast, improvement was noted beginning at 2 weeks of therapy and was overall well tolerated.41-43 studies have also investigated management of other eczematous, pruritic conditions (chronic pruritus, prurigo nodularis, hand eczema, allergic contact dermatitis) with apremilast and found trends towards improvement in itch and quality of life.44-46 participants with prurigo nodularis saw a 15% improvement in visual analog scale (vas) for itch and a 21% improvement in the dlqi as well as a trend in decreasing interleukin 10 (il-10) and il-31 expression over 12 weeks, however the changes were not statistically significant.44 separately, 66% of participants with chronic pruritus saw resolution of their itch over 16 weeks with material improvement in dlqi.45 however, results were not statistically significant likely skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 210 due to a small sample size, exacerbated by 7 participants withdrawing early (5 due to non-serious teae).45 interestingly a small open-label trial found apremilast 20 mg bid improved easi scores by 42% for patients with acd over 12 weeks with limited teae.40 cutaneous sarcoidosis an open-label trial found that apremilast 20 mg bid significantly improved cutaneous sarcoidosis (as measured by the sarcoidosis activity and severity index (sasi) and investigator-visual evaluation) within 12 weeks although there were no changes in erythema, desquamation, or area of involvement.47 of the 15 participants, 2 patients withdrew due to nausea and “jitteriness” and 3 patients who completed the study noted relapsing and worsening of their lesions after discontinuation.47 discoid lupus erythematosus among participants with discoid lupus erythematosus (dle) who completed an open-label trial of apremilast 20 mg bid monotherapy, there was a significant improvement in cutaneous lupus erythematosus disease area and severity index (clasi) score by day 85.48 50% of participants also noted resolution of scalp lesions during the study. however, 4 of 8 participants withdrew early: 2 due to disease progression and 2 due to teaes (lichenoid reaction and neuropathy) that both resolved with discontinuation of apremilast.48 hidradenitis suppurativa several rcts, open-label trials and case series/reports have investigated apremilast for the management of hidradenitis suppurativa (hs). a rct of 20 participants with moderate hs (15 on apremilast 30 mg bid) found 53.3% achieved a 50% reduction in hidradenitis suppurativa clinical response (hiscr50) as well as significant improvement in nodules and itch within 16 weeks.[49] the authors of this rct found apremilast modulated levels of s100a12 and il-17a and il-17f, suggesting these as potential modulators of hs pathogenesis.50 furthermore, in a 2 year follow up study, of the 8 participants that achieved hiscr50, 4 patients maintained hiscr at the 1 and 2 year mark with minimal and manageable teae (primarily gastrointestinal related).51 of the 4 that discontinued, 1 discontinued due to complete resolution of symptoms, 2 due to “active pregnancy wish”, and only 1 discontinued as a result of intractable nausea after 6 months.51 an open-label trial of 20 patients found similar results with 60% reaching hiscr50 by week 24.52 in both the initial rct and open-label trial, teae were primarily gastrointestinal (nausea, diarrhea), headache, only 1 patient withdrew due to severe myalgias and arthralgias and there were no severe teae or severe infections.49,52 smaller case series (n = 9) and case reports had similar findings of significant improvement in pain and dlqi with similar safety profile.53-55 lichen planus, oral lichen planus, lichenoid dermatitis in an open-label trial of apremilast 20 mg bid, 3 out of 10 patients with corticosteroidrefractory lichen planus met the studies primary end point of improvement by ≥2 grades on the physician global assessment (pga).56 however, further examination of all participants revealed a significant improvement in lesion count, target area lesion severity score (talss), itch and dlqi within 12 weeks.56 1 of 10 participants also had oral involvement and had material decrease in buccal lesions (40% to 12% surface area).56 4 weeks after discontinuation of apremilast, no significant difference was noted in study end points.[56] there were no serious teae, though 1 participant did develop asymptomatic skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 211 antinuclear antigen (ana) positivity during the study.56 several case series and reports have found apremilast was also effective in managing oral lichen planus with improvement within 2-4 weeks of initiation with only minor teaes that were adequately managed with dose reduction to 30 mg daily without compromising efficacy.57-59 a final case series of 5 patients found apremilast was effective in halting (3/5) and even resolving (2/5) lichenoid and interface dermatitis without inducing severe teae.60 rosacea an open-label trial investigated the use of apremilast 20 mg bid for the management of erythematotelangiectasia (etr) and papulopustular (ppr) rosacea among 10 participants with moderate to severe disease.61 by 12 weeks, there was a significant decrease in pga, etr rating overall erythema, and nontransient erythema with the latter two persisting for 1 month after discontinuation of therapy. no difference was found in number of papules/pustules at the end of the study versus baseline.61 overall, apremilast was well tolerated with only 2 urinary (uti) and upper respiratory tract (uri) infections neither of which necessitated dose decrease or drug withdrawal.61 vitiligo a rct investigating apremilast and narrowband ultraviolet b (nbuvb) phototherapy for the management of vitiligo failed to meet its primary endpoint and found no significant difference at either 24 or 48 weeks between vitiligo area and severity index (vasi) score, vitiligo extent score (ves), vitiligo european task force (vetf) score, or dlqi between apremilast and nbuvb and placebo and nbuvb.62 interestingly, a split-body trial investigated the combination of apremilast and narrow-band uvb (nbuvb) 2-3 times weekly for the management of vitiligo in darker phototypes (fitzpatrick iv-vi).63 over 3 phases, each lasting 16 weeks, patients receiving combination apremilast and nbuvb therapy had a significantly greater improvement in primary endpoint of >50% repigmentation (p=.001) and vitiligo area and severity index (vasi) (p=.0001) than nbuvb monotherapy.63 in the rct, authors note 2 serious side effects, 1 being a suicide attempt that was attributed to apremilast treatment while the split-body study noted a majority of drug withdrawal were due to noncompliance with nbuvb regimen and reported no serious teaes.62,63 a case series of 13 patients found 61.5% achieved at least partial repigmentation (with as needed topical tacrolimus) and a 7.1% reduction in vasi.64 additional case reports have found improvement in both recalcitrant acral and generalized vitiligo without lasting or serious teaes.65,66 case series and reports detailing efficacy of apremilast for off-label dermatoses palmoplantar pustulosis although once considered a subtype of palmoplantar psoriasis, beginning in 2007 palmoplantar pustulosis has been deigned its own entity.67 although several studies, including rcts and open-label trials, have shown efficacy for multiple biologic and nonbiologic therapies for palmoplantar psoriasis, there is less rigorous information for palmoplantar pustulosis, including with regards to apremilast.67 several retrospective observational studies, including two case series of 10 and 3 patients found that after 2 weeks of apremilast 30 mg bid, there was significant improvement in both signs and symptoms of palmoplantar pustulosis, including ~62% improvement in palmoplantar psoriasis area and severity index (pppasi) score, 66% reduction in number of pustules, and 66% in dlqi score.68-72 furthermore, the median skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 212 table 3. randomized-control trials and open-label trials for off-label uses of apremilast. study condition study type & size (n on apremilast) mean age (sd); %male dosage duration (wks) results teae mikhaylov et al32 alopecia areata rct (20) 37.1 (14.4); 20 30 mg bid 24 1/20 achieved at least salt50 improvement not significantly different from placebo (p=0.38) 3 early d/c due to teae nausea (4), diarrhea (3), uri (1), tinea pedis (1), arthralgia (1) simpson et al38 atopic dermatitis rct (58) 39.2 (--); 53.4 30 mg bid 12+12 31% achieved easi50 by week 12 vs 32.8% on placebo. not significantly different than placebo, though trend towards increased clinical improvement. higher incidence of le cellulitis (6 total, 2 serious) in 40 mg group leading to d/c of treatment arm in study. teae in >5% participants: diarrhea, nausea, headache, nasopharyngitis, uri, abdominal discomfort, cellulitis, dyspepsia serious teae: 30 mg: scc (1), pna (1) 40 mg: si (1), cellulitis (2), gn (1) simpson et al38 atopic dermatitis rct (63) 38.3 (--); 49.2 40 mg bid 12+12 significant improvement in easi score (31.6% vs 11.0% p<.04) and dlqi 27.3% vs 2.7%, p<0.05) by week 12 vs placebo, decrease in inflammatory markers (k16, p<.001; ki67+ cells, p<.001; th17 and th17/22 markers, p<.05) samrao et al39 atopic dermatitis open-label trial (6) 38 (--); 83 20 mg bid 12 significant improvement in vas pruritus (p=.02) and dlqi (p=.003) 1 early d/c: herpes zoster(1) nausea(2), loose stool(3), uri(2), headache(2) samrao et al39 atopic dermatitis open-label trial (10) 45 (--); 50 30 mg bid 24 12 weeks: significant improvement in easi (p=.008) and dlqi (p=.01). 24 weeks: significant improvement in easi (p=.002), vas (p=.003), and dlqi (p=.001) nausea(9), loose stools(4), uri(3), other infection(3), headache (2) disease flare requiring rescue topical therapy (2) volf et al40 atopic dermatitis open-label trial (5) 43 (14.5); 40 20 mg bid 16 20% worsening in easi 4 early d/c: 2 d/t worsening ad, 2 due to non-adherence volf et al40 allergic contact dermatitis open-label trial (4+1 acd & ad) 43.6 (15.7); 60 20 mg bid 12 42% reduction in easi 40% at least easi50 1 early d/c: d/t worsening of acd skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 213 clark et al45 chronic pruritus open-label trial (10) 75 (--); 40 30 mg bid 16 no significant difference in nrs itch or dlqi. of note: 2/3 patients completed study noted material improvement in nrs itch (9.5 and 8 to 0) and dlqi. 7 d/c: teae(5), resolution of itch(1), use of prohibited tx(1) nausea(3), diarrhea(3), headache(1), presyncope(1) baughman et al47 cutaneous sarcoidosis open-label trial (15) - (--); 6.7 20 mg bid 12 significantly decreased sasi induration at 4 weeks(p<.002) and 12 weeks(p<.005). improved investigator-visual evaluation (p<.02) 2 patients decreased dose to 20 mg daily due to “jitteriness”(1) and nausea (1) de souza et al48 dle open-label trial (8) 47.1 (12.3); 12.5 20 mg bid ~12 significant improvement in clasi score by day 85 (p=.01) and among patients that completed study (p=.03) 2/4 patients with complete regression of scalp lesions 4 early d/c: 2 d/t teae, 2 d/t disease progression nausea (4), diarrhea (1), headache (2), lichenoid dermatitis (1), neuropathy (1) vossen et al49 hs rct (15) 35.7 (13); 20 30 mg bid 16 53.3% on apremilast achieved hiscr50 vs 0% of placebo significant improvement in nodules (p=.011), nrs pain (p=.009), nrs itch (p=.015) no significant difference in dlqi 2 d/c: personal socioeconomic issues(1), severe myalgia/arthralgia(1) headache (7), diarrhea (7) nausea (4), vomiting (2), depressed feeling (1), non-serious infections (5), sore throat (1), pyelonephritis (1) kerdel et al52 hs open-label (20) 32.5 (10); 30 30 mg bid 24 60% achieved hiscr50 diarrhea (4), nausea (3), uri (2), depression (2), si (1), abscess (1), uti (1) paul et al56 lp open-label (10) 48.8 (12.8) 20 mg bid 12 3/10 achieved primary end point. significant decrease in lesion count (p=.002), pga (p=.0078), talss (p=.0078), svas (p=.0059) and dlqi (p=.002) headache (4), new-onset ana positivity (1) todberg et al44 prurigo nodularis open-label trial (10) 61.7 (10); 50 -12 no significant improvement over 12 weeks mean vas pruritus improvement from 8.7 to 7.4 mean dlqi improvement 11.2 to 8.8 3 d/c: 2 due to lack of efficacy, 1 due to intermittent fever diarrhea, nausea, abdominal pain in 5 patients, recurrent fever (1) skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 214 thompson et al61 rosacea open-label trial (10) 39-74 yo; 30 20 mg bid 12 significant decrease in pga (p=.02), overall erythema (p=.001), etr rating (p=.005) and nontransient erythema (p=.04) uti(2), uri(2) kemis et al62 vitiligo rct (38) 49.5 (13.4); 36.8 30 mg bid & nbuvb 52 no significant difference in vasi, vef, vetf, or dlqi between apremilast and placebo 2 serious teae: suicide attempt (1), benign amygdala tumor (1) diarrhea, abdominal pain, headache kim et al63 vitiligo rct split-body (23) --; - 30 mg bid & nbuvb 48 apremilast and nbuvb increased probability of >50% repigmentation (p=.001), improved vasi (p=.0001) compared to nbuvb monotherapy 14 d/c, majority due to noncompliance with nbuvb, teae (4) ana – anti-nuclear antibody; ad – atopic dermatitis; clasi – cutaneous lupus erythematosus disease area and severity index; d/c – discontinued; dle – discoid lupus erythematosus; dlqi – dermatology life quality index; easi eczema area and severity index; gn – glomerulonephritis; hs – hidradenitis suppurativa; hiscr hidradenitis suppurativa clinical response; hiscr50 – 50% reduction in hidradenitis suppurativa clinical response; le – lower extremity; nrs itch– numeric rating scale itch; nrs pain – numeric rating scale pain; pga – physician global assessment; pna – pneumonia; rct – randomized-control trial; salt50 – 50% reduction in severity of alopecia tool; sasi – sarcoidosis activity and severity index; scc – squamous cell carcinoma; si – suicidal ideation; svas – subject visual analog scale for itch; talss – target area lesion severity score; tx – treatment; uri – upper respiratory tract infection; uti – urinary tract infection; vas – visual analog scale; vasi – vitiligo area and severity index; vef – vitiligo extent score; vetf – vitiligo european task force score skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 215 table 4. case series: off-label dermatoses and apremilast. 18 case series listed alphabetically by dermatosis. study condition sample size (n) mean age (sd); %male dosage duration weeks (sd) results teae taneja et al33 alopecia areata 15 25.8 (3.2); 86.7 30 mg bid (n=4) 30 mg daily (n=11) 37.2 (13.6) 15/15 patients noted hair regrowth, 13/15 with >50% response, 4/15 with >75% response gastrointestinal sideeffects (nausea, diarrhea, vomiting)(11) that lead to dose decrease weber et al34 alopecia areata 5 34.8 (13.0); 0 30 mg bid 24 1/5 responded with regrowth lasting 18 months, 2/5 had slight transient regrowth, 2/5 without response nausea (3), diarrhea(1) liu & king35 alopecia areata 9 38.8 (21.4); 44.4 30 mg bid 16.8 (4.8) 8/9 patients without improvement 1/9 with increased hair loss at 6 months - abrouk et al41 atopic dermatitis 5 50.2 (10.8); 80 30 mg bid 18.4 (16.3) noticeable improvement in 2-4 weeks 4/5 patients with ≥75% improvement nausea(1), weight loss(1), pancreatitis(1, unrelated) qiblawi et al73 calcinosis cutis 2 66 f 59 f 30 mg bid* 30 mg bid† 24 12 improvement noted within 8 weeks softening of plates of calcifications leading to calcium fragment extrusion decreased dose and later discontinued due to recurrent infections at calcification areas - bitar et al74 dermatomyositis 3 57 f 64 f 62 f 30 mg bid‡ 104 12 36 cdasi 43 à0 muscle improvement cdasi 41 à7, able to taper off other tx cdasi 62 à18 nausea(1), diarrhea(1) - d/c treatment after flare and transitioned to ivig narang et al75 erythema nodosum leprosum 2 34 m 31 m 30 mg bid 30 mg bid 20 12 resolution of constitutional symptoms and significant improvement in skin lesions in 2 weeks significant improvement in 4 weeks, and no new lesions 3 months after selfdiscontinuing - - skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 216 bishnoi et al76 granuloma annulare 4 ~60 f ~43.3 (5.8); 0 30 mg bid 30 mg bid 12 6-8 significant response within 6 weeks, almost clear by 12 weeks significant response within 6-8 weeks mild diarrhea, myalgia myalgia, nausea kieffer et al77 hailey-hailey disease 4 52.5 (5);25 30 mg bid 26 (4) 3/4 achieve pga 1 after 6 months, 1/4 achieve pga 1-2 after 5 months diarrhea (2), myalgia (1) requiring dose reduction to 30 mg daily weber et al52 hidradenitis suppurativa 9 44.3 (13.5); 66.6 30 mg bid range: 2 days – 36 weeks significant reduction in sartorius score (p=.028), pain (p=.026) and dlqi (p=.021) 3 d/c due to teae: gerd(1), depression(1), insurance coverage(1) weight loss(2), nausea (1), loose stool (1), dry cough (1) bettencourt57 lp (oral) 3 70 (3.6); 100 30 mg bid 18.7 (6.1) improvement noted within 2-4 weeks. 1/3 required intermittent prednisone for flares. 3/3 eventually had complete resolution of oral lesions 1/3 nausea and diarrhea requiring dose decrease to 30 mg daily ravichandran & kheterpal60 lichenoid & interface dermatitis 5 50.8 (18.0); 0 30 mg bid 52.8 (32.3) 3/5 no new lesions on apremilast 2/5 near complete remission on apremilast 1 patient decrease dose to 30 mg daily due to teae; 2 patient d/c due to insurance denial of coverage diarrhea(2), nausea(2), uri(1), weight loss(1), vomiting(1) hadi & lebwohl78 lpp/ffa 4 58.8 (21.2); 0 30 mg bid - 2/4 improvement in scalp inflammation and pruritus in 12 weeks 2/4 with minimal improvement, teae lead to dose decrease then d/c gastrointestinal discomfort (3), depressive symptoms (1) kaushik et al79 orofacial granulomatosis 5 33 (14.5); 40 30 mg bid 12 4/5 with response, 3/5 with significant reduction in labial swelling and erythema diarrhea (2), headache (2), vomiting kato et al68 palmoplantar pustulosis 10 median: 63.7; 20 30 mg bid 15.1 (5.9) after 2 weeks, mean improvement pppasi 61.9% (p=.013), pc decrease 66% (p=.029), dlqi 66% (p = .009), vas itch 62.5% (p=.026). median 6.9 weeks to pppasi50 and 2.9 weeks to 3 d/c due to diarrhea 2 decrease dose to 30 mg daily due to diarrhea 1 transiently decrease dose then resumed 30 skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 217 pc50 mg bid due to itch frequent bowel movement (8), diarrhea (6), weight loss (3), palpitations (1), headache (1) eto et al69 palmoplantar pustulosis 3 51.7 (10.7); 0 30 mg bid 32 near complete resolution after 2 weeks mild epigastric discomfort (1) cohen et al80 seborrheic dermatitis 3 46 (20.5); 66 30 mg bid 12 results notable within 3 months, complete clearance in 1 patient, 2 with mild localized sd nausea (1) majid et al64 vitiligo 13 33.8 (12.2); 61.5 30 mg bid & as needed tacrolimus 12 61.5% of participants achieving partial repigmentation, including in areas without topical medication usage mean vasi reduction 7.1% (p<.04) headache, nausea, vomiting, abdominal pain 2/13 patients -indicates data not explicitly available. if dosage missing, implied 30 mg bid *in addition to topical and intralesional sodium thiosulfate, pentoxifylline, minocycline, amlodipine, percutaneous ultrasonic lithotripsy †in addition to topical and intralesional sodium thiosulfate, diltiazem, pentoxifylline, minocycline, surgical extraction of calcium fragments ‡in addition to prior regimen: mycophenalate mofetil and prednisone (3), and hydroxychloroquine(1) bid – twice daily; cdasi – cutaneous dermatomyositis activity and severity index; d/c – discontinued; dlqi dermatology-life quality index; gi – gastrointestinal; gerd – gastroesophageal reflux disorder; hs – hidradenitis suppurativa; ivig – intravenous immunoglobulin; lp – lichen planus; lpp/ffa – lichen planopilaris/frontal fibrosing alopecia; m – male; mg – milligrams; pga – physician global assessment; pppasi – palmoplantar psoriasis area and severity index; pppasi50 – 50% reduction in pppasi; pc – pustule count; pc50 – 50% reduction in pc; sd – standard deviation; teae – treatment-emergent adverse effect; uri – upper respiratory tract infection; vasi – vitiligo area and severity index skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 218 time to 50% reduction in pppasi and pustule count was 6.9 and 2.9 weeks, respectively.68 of note, there were 5 participants in the 10-participant trial that withdrew (n = 3) or required dose reduction (n = 2) during the study due to diarrhea.68 additional dermatoses the combination of apremilast’s unique mechanism of action, safety profile (especially compared to other non-biologic systemic agents) as well as no need for regular laboratory monitoring have piqued interest in its use for a wide breadth of other dermatoses including (and likely not limited to): acrodermatitis continua of hallipeau, calcinosis cutis, chronic actinic dermatitis, dermatomyositis, erythema nodosum leprosum, folliculitis decalvans, granuloma annulare, hailey-hailey disease, lichen planopilaris/frontal fibrosing alopecia, orofacial granulomatosis, anti-lamin γ1 (p200) pemphigoid, pemphigus vulgaris, pityriasis rubra pilaris, pyoderma gangernosum, seborrheic dermatitis, sapho, and vitiligo (table 4 and 5).73-96 in these cases, apremilast has had material effect for patients with refractory disease to first and second line treatment and, surprisingly, is often used successfully as monotherapy. although only fda-approved for psoriasis, psoriatic arthritis and behçet’s disease, apremilast’s mechanism of action has proven to have sustained efficacy for multiple inflammatory dermatoses without increasing rates of serious teaes. many of the studies demonstrated apremilast’s efficacy especially for psoriasis for which fda-approved first (and second line) therapies may have lost efficacy18-31 or for other moderate to severe dermatoses that were not suitably managed long-term by corticosteroids, or other non-biologic systemic agents32-96. in several cases, apremilast had the same relatively rapid onset of activity (~2-4 weeks) as seen in psoriasis, despite the various diverging types of inflammatory conditions treated.41,42,47,55,57,68,69,70,72,75,81,84,87,91,93 furthermore, studies that investigated changes in known cytokine cascades suggest that apremilast and pde-4 inhibition may achieve its efficacy by targeting inflammatory mediators unaffected or not primarily affected by current first-line agents.36-40,42,43,46,49,54,55,58,59,65,66,81-96 in addition to efficacy, consideration should be given to apremilast’s safety profile. while gastrointestinal teaes (most commonly nausea, diarrhea, vomiting), weight loss and headache do occur, they are often transient or manageable with dose modification.33,37,42,47,57,58,60,68,72,77 while several infections were documented across the collected studies, they usually occurred as a result of comorbid conditions (e.g., diabetes)38 and were predominately not severe infections. while depressive symptoms have been noted, in all the reviewed studies only 1 case was suicidal ideation/attempt directly associated with apremilast therapy.62 additional studies have investigated the association of depression with apremilast and continually noted its safety regarding mental health.9 the safety profile is further highlighted by the fact that regular laboratory monitoring is not needed nor required for patients on apremilast.1,67 taken together, apremilast has several unique characteristics that make it an attractive potential complementary or alternative therapeutic option for patients that are adverse to or are not ideal discussion skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 219 table 5. case reports: off-label dermatoses and apremilast. 30 case reports listed in alphabetical order by dermatosis. study condition age, sex dosage duration weeks results teae magdaleno-tapial et al36 alopecia areata 52 f -15 regrowth of eyelashes and scattered scalp hair - chhabra et al37 alopecia totalis 11 m 30 mg qam, 10 mg qpm & plate-rich plasma 24 improved - saporito and cohen42 atopic dermatitis 8 m 30 mg daily 8 improvement noted starting at 2 weeks - farahnik et al43 atopic dermatitis + alopecia areata 55 m 30 mg bid 10 subjective improvement in pruritus in 4 weeks with substantial decrease in erythema and stabilization of hair loss with some scalp hair regrowth in 10 weeks transient nausea and “gas” calleja algarra et al81 acrodermatitis continua of hallopeau 75 m 30 mg bid 24 improvement noted within 1 month, persistent improvement in onychodystrophy noted at 6 months georgakopoulos et al82 acrodermatitis continua of hallopeau 68 m 30 mg bid & infliximab 5mg/kg every 8 weeks 24 used as maintenance, minimal onychodystrophy at 6 month follow up - lanna et al83 acrodermatitis continua of hallopeau 58 m 30 mg bid 4 dlqi improved from 10 to 0 over 4 weeks - kaushik et al84 chronic actinic dermatitis 36 f 30 mg daily & low-potency topical and oral corticosteroids 12 significant improvement in 4 weeks with clearance by 6 weeks - charlton et al85 dermatomyositis ~50 f 30 mg bid & prednisone 7.5 mg/d, diltiazem 120 mg daily, yearly zolendronate 28 resolution of heliotrope rash, facial erythema, scalp pruritus. no change in cutaneous calcinosis - sanchez-martinez et al86 erythema nodosum leprosum 23 f 30 mg bid 24 asymptomatic by 6 month follow up self-limited headache, mild diarrhea fassler et al87 folliculitis decalvans 28 m - & as needed 2% chlorhexidine shampoo 25 significant nearly complete remission by 3 weeks - di altobrando et hailey-hailey 68 f -144 significant remission without further - skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 220 al88 disease application of topical corticosteroids navarro-trivino et al46 hand eczema pruritus 65 m 30 mg bid 4 improved - garcovich et al54 hs (+ psa) 73 m 51 m 30 mg bid 30 mg bid 16 16 improved hs-pga: 4 à 2 improved dlqi: 23 à 6 improved hs-pga: 5 à 3 improved dlqi: 25 à 9 none by 60 weeks none by 72 weeks lanna et al55 hidradenitis suppurativa (+pso) 55 m 30 mg bid pasi95, hurley stage decrease 2 to 0-1 and dlqi from 22 to 0 within 20 days - abuhilal et al58 lp (oral) 44 f 30 mg daily 12 improvement in buccal/gingival lesions nausea with 30 mg bid hafner et al59 lp (oral), esophageal stenosis 74 f -4 complete resolution of dysphagia and erosive stomatitis - haebich & kalavala70 palmoplantar pustulosis 75 f 30 mg bid ~52 resolved within 4 weeks - haller et al71 rituxmimabassociated palmoplantar pustulosis 57 f 30 mg bid significant improvement within 6 weeks - carrascosa et al72 palmoplantar pustulosis 77 f 30 mg daily ~52 near complete resolution of pain/pustules within 2 weeks mild diarrhea resolved with dose reduction from bid to daily waki et al89 anti-lamin γ1 (p200) pemphigoid (+ pso) 57 m 60 mg daily & prednisolone taper (30 mg/d to 15 mg/d) ~36 able to taper prednisolone 2.5 mg ever 5-7 weeks without flare - meier et al90 pemphigus vulgaris 62 f 30 mg bid & 2 mg mycophenolate mofetil and 20 mg prednisone 32 absis 38à0 reduction in anti-dsg1 and antidsg3 antibodies and increase in treg and tfreg cells - krase et al91 prp 70 m 30 mg bid 32 initial improvement noted within 4 weeks with complete resolution within 6-8 months gi upset cho et al92 prp 60 f 30 mg daily 24 complete resolution at 8 weeks, mild headache skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 221 sustained at 24 weeks pellonnet et al93 prp 47 m 30 mg bid 28 complete resolution at 4 weeks, sustained to 28 weeks - molina-figuera et al94 prp 61 f 30 mg bid 28 near complete clearance at 8 weeks and able to discontinue at 28 weeks due to resolution. remained symptoms free 12 weeks after d/c - vernero et al95 pyoderma gangrenosum 35 m - & prednisone and vedolimumab for crohn’s disease 19 consistent improvement in pain and lesion re-epithelialization at 15 weeks - adamo et al96 sapho 24 f 30 mg bid 28 92.3% reduction in pppasi transient headache, diarrhea, nausea, vomiting resolved within 4 weeks plachouri et al65 vitiligo (+ pso) 59 m 30 mg bid 24 repigmentation of vitiligo on neck and trunk without much affect at extremities. near complete clearence of pso plaques - huff & gottwald66 vitiligo 52 f 30 mg bid & im triamcinolone 60 mg 52 slow repigmentation proximal to distal over 6.5 months, 60-70% repigmentation on face, chest arms by 11 months - -indicates data not explicitly available. if dosage missing, implied 30 mg bid absis – autoimmune bullous skin disorder intensity score; bid – twice daily; dlqi dermatology-life quality index; dsg – desmoglein; gi – gastrointestinal; hs-pga – hidradenitis suppurativa-physician global assessment; lp – lichen planus; m – male; mg – milligrams; f – female; pppasi – palmoplantar psoriasis area and severity index; prp – pityriasis rubra pilaris; psa – psoriatic arthritis; pso – psoriasis; qam – every morning; qpm – every afternoon/evening; sapho – synovitis, acne, pustulosis, hyperostosis and osteitis; teae – treatment-emergent adverse effect; treg – regulatory t-cell; tfreg – follicular regulatory t-cell skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 222 candidates for current therapies. additional studies may further elucidate ways apremilast monotherapy and combination therapy, especially in the setting or recalcitrant psoriatic arthritis, may be used to improve patient care and outcomes for psoriasis and other inflammatory dermatoses. apremilast is an oral, non-biologic systemic agent that inhibits phosphodiesterase 4 activity to modulate inflammation. while transient gastrointestinal side effects are common, especially early-on in therapy, it has a relatively innocuous safety profile that makes it a potential efficacious agent for monotherapy and combination therapy for a wide range of inflammatory dermatoses. conflict of interest disclosures: jwm has no relevant disclosures. mgl is an employee of mount sinai and receives research funds from: abbvie, amgen, arcutis, boehringer ingelheim, dermavant, eli lilly, incyte, janssen research & development, llc, leo pharmaceutucals, ortho dermatologics, pfizer, and ucb, inc.and is a consultant for aditum bio, allergan, almirall, arcutis, inc., avotres therapeutics, birchbiomed inc., bmd skincare, boehringer-ingelheim, bristol-myers squibb, cara therapeutics, castle biosciences, corrona, dermavant sciences, evelo, facilitate international dermatologic education, foundation for research and education in dermatology, inozyme pharma, kyowa kirin, leo pharma, meiji seika pharma, menlo, mitsubishi, neuroderm, pfizer, promius/dr. reddy’s laboratories, serono, theravance, and verrica. funding: none corresponding author: justin w. marson, md department of dermatology suny downstate health sciences university brooklyn, ny, 11203 fax: 732-802-7207 email: justin.w.marson@gmail.com references: 1. 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(2019). refractory cutaneous dermatomyositis with severe scalp pruritus responsive to apremilast. jcr: journal of clinical rheumatology, 1. doi:10.1097/rhu.0000000000000999 86. sánchez-martínez, e. m., melgosa-ramos, f. j., moneva-léniz, l. m., gegúndez-hernández, h., prats-máñez, a., & mateu-puchades, a. (2020). erythema nodosum leprosum successfully treated with apremilast: more effective and safer than classic treatments? international journal of dermatology. doi:10.1111/ijd.15205 87. fässler, m., radonjic-hoesli, s., feldmeyer, l., imstepf, v., pelloni, l., yawalkar, n., & de viragh, p. a. (2020). successful treatment of refractory folliculitis decalvans with apremilast. jaad case reports, 6(10), 1079– 1081. doi:10.1016/j.jdcr.2020.08.019 88. di altobrando, a., sacchelli, l., patrizi, a., & bardazzi, f. (2020). successful treatment of refractory hailey-hailey disease with apremilast. clinical and experimental dermatology. doi:10.1111/ced.14173 89. waki y, kamiya k, komine m, maekawa t, murata s, ishii n, hashimoto t, ohtsuki m. a case of anti-laminin γ1 (p200) pemphigoid with psoriasis vulgaris successfully treated with apremilast. eur j dermatol. 2018 jun 1;28(3):413-414. doi: 10.1684/ejd.2018.3280. pmid: 29619999. 90. meier, k., holstein, j., solimani, f., waschke, j., ghoreschi, k., 2020. case report: apremilast for therapy-resistant pemphigus vulgaris. frontiers in immunology 11.. doi:10.3389/fimmu.2020.588315 91. krase, i.z., cavanaugh, k., curiel-lewandrowski, c., 2016. treatment of refractory pityriasis rubra pilaris with novel phosphodiesterase 4 (pde4) inhibitor apremilast. jama dermatology 152, 348.. doi:10.1001/jamadermatol.2015.3405 92. cho, m., honda, t., ueshima, c., kataoka, t., otsuka, a., kabashima, k., 2018. a case of pityriasis rubra pilaris treated successfully with the phosphodiesterase-4 inhibitor apremilast. journal of rehabilitation medicine 98, 975–976.. doi:10.2340/00015555-2995 93. pellonnet l, beltzung f, franck f, rouanet j, d'incan m. a case of severe pityriasis rubra pilaris with a dramatic response to apremilast. eur j dermatol. 2018 feb 1;28(1):128-129. doi: 10.1684/ejd.2017.3187. pmid: 29400288. 94. molina-figuera, e., gonzález-cantero, á., martínez-lorenzo, e., sánchez-moya, a.-i., garcía-olmedo, o., gómez-dorado, b., & schoendorff-ortega, c. (2018). successful treatment of refractory type 1 pityriasis rubra pilaris with apremilast. journal of cutaneous medicine and surgery, 22(1), 104– 105. doi:10.1177/1203475417733464 95. vernero, m., ribaldone, d. g., cariti, c., ribero, s., susca, s., astegiano, m., & dapavo, p. (2020). dual-targeted therapy with apremilast and vedolizumab in pyoderma gangrenosum associated with crohn’s disease. the journal of dermatology. doi:10.1111/1346-8138.15283 96. adamo, s., nilsson, j., krebs, a., steiner, u., cozzio, a., french, l. e., & kolios, a. g. a. (2018). successful treatment of sapho syndrome with apremilast. british journal of dermatology. doi:10.1111/bjd.16071 skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 48 brief article demodicosis mimicking papulopustular eruption in the setting of targeted therapy iulianna taritsa, ba1, shikha walia, bs2, jennifer n. choi, md1 1 northwestern university feinberg school of medicine, chicago, il 2 lake erie college of osteopathic medicine, erie, pa here we discuss the dramatic cutaneous reactions of two patients receiving targeted therapies for cancer (one on a mek inhibitor/braf inhibitor and the other receiving carfilzomib). a woman in her 50s receiving vemurafenib 480mg twice daily and trametinib 2mg daily for anaplastic astrocytoma presented to oncodermatology clinic with a 6-month history of persistent papulopustular eruption involving the face and scalp. pink papules and pinpoint pustules were noted on the forehead, nose, cheeks, upper lip and chin one week after beginning targeted therapy (figure 1a). inflamed papules were scattered across the lateral and posterior neck and scalp. the lesions were not pruritic nor painful. she received doxycycline 100mg twice daily and triamcinolone 0.1% cream for the face and fluocinonide 0.05% solution for the scalp for suspected cutaneous reaction to mek inhibitor/braf inhibitor (brafi/meki) therapy. her eruption persisted over the next five months despite treatment with various oral antibiotics, topical antibiotics, and topical steroids. while mineral preparation of scrapings of active facial pustules did not reveal any organisms, the patient began treatment for presumed demodex folliculorum folliculitis using ivermectin 15mg (two doses, 1 week apart). remarkable improvement of the eruption was seen 10 days later. she then started a topical compounded cream including metronidazole 1%, ivermectin 1%, and azelaic acid 15% for daily use until complete resolution. one month later, her face was clear (figure 1b). abstract here we discuss the dramatic cutaneous reactions of two patients receiving targeted therapies for cancer (one on a mek inhibitor/braf inhibitor and the other receiving carfilzomib). demod icosis was the underlying cause in both cases, though the infection was mistaken for a reaction to the patients’ complex malignancy therapies. given the prevalence of cutaneous side effects of chemotherapy and targeted cancer therapies and the protean nature of demodicosis, it follows that demodicosis may be easily mistaken as a drug reaction to a chemotherapeutic agent. demodicosis in the setting of chemotherapy and immunosuppression must thus remain an important diagnostic consideration in patients undergoing cancer treatment to allow for appropriate diagnosis and management of cutaneous findings without discontinuation of essential chemotherapy. introduction case reports skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 49 figure 1. patient receiving vemurafenib and trametinib daily for anaplastic astrocytoma a) one week after starting targeted therapy. pink papules and pinpoint pustules noted on the forehead, nose, cheeks, upper lip and chin b) remarkable improvement of cutaneous events 10 days after starting ivermectin for demodicosis. a man in his 50s receiving proteasome inhibitor carfilzomib 54mg/m2 one dose every two weeks for multiple myeloma presented with a new onset facial rash consisting of 2-4 mm pink follicular papules on the face, neck, and scalp. the patient endorsed temporary improvement with 1g doses of methylprednisolone with every carfilzomib infusion. he initiated treatment with clobetasol 0.05% cream twice daily for 2 weeks with some improvement. two months later, approximately two weeks after switching therapy to daratumumab, he was hospitalized for cancer-related complications and worsening pruritic facial eruption. his physical exam revealed excoriated, erythematous, folliculocentric papules, deep nodules, and pustules on the bilateral temples, cheeks, ears, scalp, forehead, and posterior neck (figure 2a). mineral scraping of pustules revealed no organisms. punch biopsy showed deep suppurative inflammation with dermal neutrophilic infiltrate, and demodex mites (fig 3). he received 15mg of oral ivermectin (two doses, 1 week apart) for the treatment of demodicosis, achieving complete resolution at two-week follow-up (fig 2b). figure 2. patient receiving carfilzomib, one dose every two weeks, then daratumumab for multiple myeloma a) two weeks after starting daratumumab. erythematous, folliculocentric papules, deep nodules, and pustules on the bilateral temples, cheeks, ears, scalp, forehead, and posterior neck b) significant resolution seen two weeks after starting ivermectin for demodicosis. demodex mites (demodex folliculorum and brevis) are commensal organisms that colonize sebaceous areas. a range of facial inflammatory eruptions may be seen when the mites proliferate, including pustular folliculitis and conditions that mimic pityriasis folliculorum1, papulopustular rosacea, granulomatous rosacea, periorificial dermatitis, acne, blepharitis, and papulopustular scalp eruptions2. infection incidence increases among the elderly or immunocompromised patients, including those with hiv and those receiving immunosuppression for cancer treatment3. demodicosis has been associated with several immunomodulatory agents, including topical or systemic steroids, monoclonal antibody therapies like cetuximab and panitumumab4, and biologics like dupilumab5. these therapies are hypothesized to reduce the body’s defense against mite proliferation while simultaneously upregulating chemokines discussion skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 50 that recruit mast cells and macrophages, potentiating an inflammatory response4. figure 3. results of punch biopsy from the patient seen in figure 2. biopsy shows deep suppurative inflammation with dermal neutrophilic infiltrate, and demodex mites. our cases add to the literature of demodicosis following immunomodulatory therapy. the combination of brafi/meki has revealed distinct dermatologic toxicities, potentially due to brafi’s action on mapk signaling and increased braf signaling6. the co-administration of a meki has been speculated to limit adverse effects by reducing mapk/craf pathway activation7. however, patients on dual therapy still experience maculopapular eruptions, papulopustular eruption, epidermal hyperkeratosis in the form of verrucous keratoses8 and keratosis pilaris9, and keratoacanthomas. proteasome inhibitors like carfilzomib have also been reported to cause cutaneous eruptions, including papulonodular eruptions, urticaria, cutaneous vasculitis8, and sweet syndrome9. these exanthematous reactions are believed to be the result of cell-mediated delayed hypersensitivity10. to our knowledge, demodicosis mimicking papular eruptions associated with brafi/meki or proteasome inhibitors has previously been reported. the diagnosis of demodicosis can be made via skin scraping with mineral or koh preparation or skin biopsy showing organisms within hair follicles (see fig. 3)11. the diagnostic value of microscopic examination of sebaceous secretions versus standardized skin surface biopsy is debated. treatment options include topical or oral ivermectin, topical permethrin, benzoyl benzoate, and metronidazole12. the longterm use of mid-potency or stronger topical corticosteroids on the face should be highly discouraged, as these have the potential to exacerbate this condition or can result in periorificial dermatitis which has a similar clinical presentation. bacterial superinfection in the setting of demodex infection has also been observed. few reports exist that causally link brafi’s or proteosome inhibitors to demodex infection. we suspect a potential relationship between the immunomodulatory effects of targeted therapy and susceptibility to demodex, resulting in our patients’ cutaneous eruptions. demodicosis in the setting of chemotherapy and immunomodulation must remain a diagnostic consideration in cancer patients to allow for appropriate management of cutaneous findings without discontinuation of essential cancer therapy. conflict of interest disclosures: none funding: none corresponding author: jennifer n. choi, md northwestern university feinberg school of medicine chicago, illinois email: jennifer.choi@northwestern.edu references: 1. dominey a, tschen j, rosen t, batres e, stern jk. pityriasis folliculorum revisited. j am acad conclusion skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 51 dermatol. jul 1989;21(1):81-4. doi:10.1016/s0190-9622(89)70152-3 2. hsu c-kmd, hsu mm-lmd, lee jy-ymd. demodicosis: a clinicopathological study. journal of the american academy of dermatology. 2008;60(3):453-462. doi:10.1016/j.jaad.2008.10.058 3. ivy sp, mackall cl, gore l, gress re, hartley ah. demodicidosis in childhood acute lymphoblastic leukemia; an opportunistic infection occurring with immunosuppression. j pediatr. nov 1995;127(5):751-4. doi:10.1016/s00223476(95)70168-0 4. demodex inflammatory eruption due to egfr inhibitor therapy. journal of the american academy of dermatology. 2014;70(5):ab3-ab3. doi:10.1016/j.jaad.2014.01.012 5. quint t, brunner pm, sinz c, et al. dupilumab for the treatment of atopic dermatitis in an austrian cohort-real-life data shows rosacea-like folliculitis. j clin med. apr 24 2020;9(4)doi:10.3390/jcm9041241 6. su f, viros a, milagre c, et al. ras mutations in cutaneous squamous-cell carcinomas in patients treated with braf inhibitors. new england journal of medicine. 2012;366(3):207215. doi:10.1056/nejmoa1105358 7. dummer r, rinderknecht j, goldinger sm. ultraviolet a and photosensitivity during vemurafenib therapy. new england journal of medicine. 2012;366(5):480-481. doi:10.1056/nejmc1113752 8. ransohoff jd, kwong by. cutaneous adverse events of targeted therapies for hematolymphoid malignancies. clin lymphoma myeloma leuk. dec 2017;17(12):834-851. doi:10.1016/j.clml.2017.07.005 9. kim js, roh hs, lee jw, lee mw, yu hj. distinct variant of sweet’s syndrome: bortezomib‐ induced histiocytoid sweet’s syndrome in a patient with multiple myeloma. international journal of dermatology. 2012;51(12):1491-1493. doi:10.1111/j.1365-4632.2011.05141.x 10. wu kl, heule f, lam k, sonneveld p. pleomorphic presentation of cutaneous lesions associated with the proteasome inhibitor bortezomib in patients with multiple myeloma. j am acad dermatol. nov 2006;55(5):897-900. doi:10.1016/j.jaad.2006.06.030 11. forton fm, de maertelaer v. two consecutive standardized skin surface biopsies: an improved sampling method to evaluate demodex density as a diagnostic tool for rosacea and demodicosis. acta derm venereol. feb 8 2017;97(2):242-248. doi:10.2340/00015555-2528 12. jacob s, vandaele ma, brown jn. treatment of demodex-associated inflammatory skin conditions: a systematic review. dermatol ther. nov 2019;32(6):e13103. doi:10.1111/dth.13103 john hornberger 1, md, and darrell rigel 2, md, stanford university 1, stanford, ca and new york university medical center 2, new york, ny health economic implications of a noninvasive gene expression test for primary cutaneous melanoma introduction the majority (>90%) of about 2.5 million surgical biopsies performed in the us to rule out melanoma are benign and categorized as neither invasive melanomas nor melanomas in situ by histopathology. a recently described adhesive patch skin biopsy based non-invasive gene expression test (pigmented lesion assay, pla) demonstrated utility and differentiated benign from malignant pigmented skin lesions with a test performance that exceeded visual inspection (vi) and a sensitivity that matching the gold standard of dermatopathology. 1-4 however, cost and outcome implications of using this molecular test versus vi have not been evaluated. results a biopsy ratio reduction from 12.5 for vi to 2.4 for pla use was observed. the number needed to excise (nne) declined from 2.85 for vi to 1.37 for pla use. the 1.77-fold increase in specificity of pla over vi also resulted in lower costs for initial biopsy ($211), subsequent excisions ($86), surveillance management ($77), and management of melanoma ($508). there was $31 average savings from avoidance of lost work productivity, and improvement in patient experience as assessed by quality adjusted life years (gain of 0.016 years). figure 1 depicts the decision diagram. conclusion the improved accuracy of pla use versus vi led to fewer unnecessary procedures and office visits, without negative impact on the early detection of melanoma. this results in potentially reduced direct medical costs, reduced loss of work productivity and improved patient care and experience. references gerami et al., development and validation of a non-invasive 2-gene molecular assay for cutaneous melanoma; jaad-d-16-00647r1, 2016. ferris et al., utility of a noninvasive 2-gene molecular assay for cutaneous melanoma and effect on the decision to biopsy. jama dermatology, 153(7)675-680, 2107. yao et al., analytical characteristics of a noninvasive gene expression assay for pigmented skin lesions. assay and drug development technologies, 14(6)355-363, 2016. yao et al., an adhesive patch-based skin biopsy device for molecular diagnostics and skin microbiome studies. journal of drugs in dermatology, 16(10)611-618, 2017. study aim, design and methods we set out to determine potential cost savings and impact on outcome of pla use versus vi in patients with pigmented cutaneous lesions suggestive of melanoma. we performed health economic analyses from average us insurance reimbursement values comparing the real-world impact the pla may have with vi. data sources were from published clinical validation and utility studies as well as from routine use of the test in us dermatology practices, augmented by fee schedules of cms. patients with suspicious lesion melanoma “supicious” “non-suspicious” no melanoma “supicious” “non-suspicious” bx bx “positive” “negative” excision “positive” “negative” excision “malignant” “malignant” “benign” “benign” “benign” “benign” “benign” “benign” “atypia” figure 1. decision diagramsupported by dermtech, inc. 1. 2. 3. 4. fc17posterdermtechhornbergerhealtheconomicimplications.pdf skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 36 research letter addressing geographic disparities in dermatology through virtual educational outreach haya s. raef, ms1,2, maribeth hourihan, md1,2, jacob m. macdonald, bs1,2, janell lewis, ms1,2, elizabeth v. seiverling, md1,2,3 1 tufts university school of medicine, boston, ma 2 maine medical center, portland, me 3 maine medical partners dermatology, south portland, me the disparity in the geographic distribution of dermatologists between urban and rural areas continues to worsen, with many counties lacking a dermatologist1. rural origin is a strong indicator of eventual rural practice for physicians2, however students of rural background account for less than 5% of all incoming medical students3. those with a rural background who are also from underrepresented racial/ethnic minority groups in medicine (urm) make up less than 0.5% of new medical students3. increasing representation of both urm and non-urm students with rural backgrounds is important to increase the supply of dermatologists in rural areas, which have higher skin cancer mortality rates compared to urban populations4. moreover, abstract background: rural areas face significant shortage of dermatologists. rural origin is a strong indicator of eventual rural practice for physicians, however students of rural background account for less than 5% of all incoming medical students. increasing representation of students with rural backgrounds is important to increase the supply of dermatologists in rural areas, which have higher skin cancer mortality rates compared to urban populations. we created a virtual educational outreach program for high school students in maine, a predominately rural state, to create interest amongst high school students in pursuing a career in health care. methods: we developed a virtual pipeline program called the inside medicine program that provides monthly educational workshops to high school students in maine. for one of the sessions, we conducted a dermatology workshop teaching various topics in dermatology. preand post-curriculum surveys were sent to 33 students, which used a 10-point likert scale to rate interest and perceived knowledge levels in these topics. results: after the workshop, 100% of respondents endorsed a greater understanding of the path to a dermatology career and 94.12% stated that they were interested in learning more about dermatology. moreover, students endorsed greater interest in pursuing a career in dermatology and reported a significant increase in knowledge about various dermatologic topics. conclusions: our results suggest that our program has improved these students’ interest and perceived knowledge in dermatology. we hope that this will promote their subsequent entry into the medical field to address shortages in subspecialty care in rural areas. introduction skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 37 representation of minorities improves patient care because race-concordant visits are associated with greater patient satisfaction5. poor accessibility to mentors has been reported as a major barrier to pursuing dermatology6. with recognition of the need to increase diversity within medicine, we developed a virtual educational outreach program for high school students in maine. adapting to the precautions necessitated by the covid-19 pandemic, we developed a virtual pipeline program called the inside medicine program, led by a combination of medical school students, faculty and staff. the program targeted maine high school students, with a focus on urm students, to help improve supply of healthcare workers in maine, a predominately rural state with increasing minority immigrant and refugee populations. since the covid-19 outbreak, this monthly program has provided students with mentorship and educational workshops to support their interest in medicine. for one of the sessions, we developed a dermatology workshop to teach students several topics including the path to a dermatology career, acne etiology and treatment, common skin rashes, and the abcde’s of melanoma. pre and post-curriculum surveys were sent electronically to 33 students, which used a 10-point likert scale to rate interest and perceived knowledge levels in these topics. moreover, perceived barriers to a dermatology career were assessed. analysis was performed with graphpad prism 9.0. the pre-curriculum survey was completed by 25 of 33 high school students (response rate, 75.76%). twenty-one students attended the virtual dermatology workshop, and 17 completed the post-curriculum survey (response rate, 80.95%). among 25 students, 24 (96%) were female. seventeen (68%) self-identified as white, four (16%) as asian, two (8%) as african american or black, and one (4%) as mixed race/ethnicity. nine students (36%) indicated that they had a physician family member (table 1). of the nine students with physician family members, seven (77.78%) were white and two (22.2%) were non-white (black/african american or mixed race). after the workshop, 100% of respondents endorsed a greater understanding of the path to a dermatology career and 94.12% stated that they were interested in learning more about dermatology. moreover, students endorsed greater interest in pursuing a career in dermatology (pre-workshop mean [sd], 3.36 [2.92] vs post-workshop mean [sd], 5 [2.89]; p<0.05). students also reported a significant increase in knowledge about common skin rashes (pre-workshop mean [sd], 3.17 [1.62] vs post-workshop mean [sd], 7 [1.27]; p<0.01), identifying melanoma (pre-workshop mean [sd], 2.75 [2] vs post-workshop mean [sd], 8.41 [1.12]; p<0.01), and acne development and treatment (pre-workshop mean [sd], 5.21 [2.10] vs post-workshop mean [sd], 8.63 [1.20]; p<0.01). when asked about barriers toward pursuit of a career in dermatology, students cited concerns about the large financial burden of schooling, competitiveness of the field, inadequate accessibility to mentors, and the rigor and duration of the required education (figure 1). out of the 16 students with no physician family members, 14 (87.5%) reported financial burden of as a main barrier toward pursuit of a career in dermatology, methods results skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 38 compared to four out of nine students (44.44%) with physician family table 1: student demographics gender number of students, (%) female 24 (96) male 1 (4) race/ethnicity white 17 (68) black or african american 2 (8) hispanic 1 (4) asian 4 (16) mixed 1 (4) high school grade level freshman 8 (32) sophomore 4 (16) junior 8 (32) senior 5 (20) physician in family? yes 9 (36) no 16 (64) prior knowledge in dermatology? yes 1 (4) no 24 (96) prior visit to a dermatologist? yes 5 (20) no 20 (80) do you know any dermatologists in the community? yes 10 (40) skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 39 no 15 (60) figure 1. high school students’ perceived barriers to pursuit of a dermatology career members. financial burden of schooling was therefore more commonly reported in students who did not have physician family members compared to students who had physician family members (p<0.05). students in predominately rural states have fewer role models in medicine and our program aims to help them envision pursuit of a health care career. our results suggest that our program has improved these students’ interest and perceived knowledge in dermatology. it is notable that most participants in our program were female and white. although we had not advertised the program towards a specific gender, females have been shown in prior studies to be more likely to participate in extracurricular activities than boys, with the exception of athletics 7. our gender difference is also consistent with the predominance of females observed in other pipeline programs 8,9. additionally, many facets of dermatology make it an attractive specialty for women, resulting in a significant influx of women entering dermatology in recent years. while white studxsents were the largest of all racial/ethnic groups in our program, urm students represent a larger percentage in our program than is seen in maine as a whole. our program aims to continue operating in the coming years and is working further increase urm student representation through more aggressive recruitment efforts. limitations of the study include the small sample size. in addition, four of 21 students 0 10 20 30 40 50 60 70 80 90 100 too compet itive financial concerns years of educ ation difficulty of education lack of mentors and exposure s tu d e n ts . p e rc e n ta g e barrier discussion skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 40 (19.05%) who completed the workshop were lost to follow-up, so it is possible that our reported outcomes may under or overestimate the effectiveness of our program. despite these limitations, our findings lend support to pipeline efforts that broaden access to mentorship and resources in a virtual age. a follow-up study that assesses matriculation into medical school and pursuit of dermatology residency will be a valuable determinant of the long-term success of the program. it is our hope that our experience and reported outcomes will serve as a model for other programs to engage high school students from underrepresented groups and to eventually expand care in underserved non-urban areas. conflict of interest disclosures: none funding: none corresponding author: haya raef, ms tufts university school of medicine 145 harrison avenue boston, ma 02111 phone: (207)-766-1408 email: haya.raef@tufts.edu references: 1. feng h, berk-krauss j, feng pw, stein ja. comparison of dermatologist density between urban and rural counties in the united states. jama dermatol. 2018;154(11):1265-1271. 2. woloschuk w, tarrant m. do students from rural backgrounds engage in rural family practice more than their urban-raised peers? med educ. 2004;38(3):259-261. 3. shipman sa, wendling a, jones kc, kovargough i, orlowski jm, phillips j. the decline in rural medical students: a growing gap in geographic diversity threatens the rural physician workforce. health aff (millwood). 2019;38(12):2011-2018. 4. henley sj, anderson rn, thomas cc, massetti gm, peaker b, richardson lc. invasive cancer incidence, 2004–2013, and deaths, 2006–2015, in nonmetropolitan and metropolitan counties — united states. morb mortal wkly rep surveill summ. 2017;66(14):1-13. 5. cooper la, roter dl, johnson rl, ford de, steinwachs dm, powe nr. patient-centered communication, ratings of care, and concordance of patient and physician race. ann intern med. 2003;139(11):907-915. 6. soliman ys, rzepecki ak, guzman ak, et al. understanding perceived barriers of minority medical students pursuing a career in dermatology. jama dermatol. 2019;155(2):252254. 7. mcneal rb jr. high school extracurricular activities: closed structures and stratifying patterns of participation. j educ res. 1998;91(3):183-191. 8. nair n, marciscano ae, vivar kl, schaeffer s, lamont e, francois f. introduction to the medical professions through an innovative medical student-run pipeline program. j natl med assoc. 2011;103(9-10):832-838. 9. yelorda k, bidwell s, fu s, et al. self-efficacy toward a healthcare career among minority high school students in a surgical pipeline program: a mixed methods study. j surg educ. published online may 16, 2021. doi:10.1016/j.jsurg.2021.04.010 conclusion mailto:haya.raef@tufts.edu methods • human donor skin tissue samples of 500-µm thickness were pretreated with a 1440-nm or 1927-nm laser (clear + brilliant® laser system; solta medical, bothell, wa), or received no pretreatment (table 1) table 1. experimental parameters for uptake analysis • following laser pretreatment, an in-house 4% hydroquinone serum (hydrophilic formulation) was applied, and permeation was measured up to 24 hours after application (figure 1) • laser-treated skin and untreated controls were analyzed using high-performance liquid chromatography at various time points up to 24 hours after application to measure cumulative permeation and retention and to quantify uptake of 4% hydroquinone serum • total uptake was calculated as the sum of the normalized cumulative permeation and retention in each sample figure 1. study design for testing uptake of topicals on skin tissue. pbs, phosphate-buffered saline. results • pretreatment with the 1927-nm wavelength resulted in greater cumulative uptake of 4% hydroquinone serum compared to the 1440-nm wavelength and untreated control (figure 2) figure 2. cumulative permeation of 4% hydroquinone serum at 24 hours after 1440-nm and 1927-nm pretreatment. values are mean ± standard deviation. • compared to untreated controls, topical uptake was – 1.8 times greater with 1440-nm (1.2-w) pretreatment – 2.7 times greater with 1927-nm (0.6-w) pretreatment – 4.6 times greater with 1927-nm (1.0-w) pretreatment • the lower-power 1927-nm settings (0.6 and 1.0 w) were associated with 1.5and 2.6-times greater uptake, respectively, compared to 1440-nm (1.2-w) pretreatment (table 2) table 2. uptake ratios of 4% hydroquinone with various laser wavelengths and power settings synopsis • non-ablative fractional diode laser pretreatment can enhance transdermal delivery and uptake of topicals and minimize thermal side effects that are more typical of ablative laser therapy1,2 • fractionation can create microscopic treatment zones that spare surrounding tissue and further minimize postprocedural downtime1,2 • clinical practice may be improved by understanding the relationship between topical uptake and energy-device settings, such as wavelength, peak power, and spot density quantifying uptake of topical 4% hydroquinone after 1440-nm and 1927-nm non-ablative fractional diode laser treatment jordan v. wang, md, mbe, mba1; paul m. friedman, md1,2; adarsh konda, pharmd3; catherine parker, np, msn4; roy g. geronemus, md1 1laser & skin surgery center of new york, new york, ny; 2dermatology and laser surgery center, houston, tx; 3bausch health us, llc, bridgewater, nj; 4solta medical, bothell, wa objective • to quantify uptake of 4% hydroquinone serum using skin tissue pretreated with either a 1440-nm or 1927-nm non-ablative fractional diode laser conclusions • non-ablative fractional diode laser pretreatment with the 1927-nm wavelength resulted in greater uptake of hydrophilic 4% hydroquinone serum compared to the 1440-nm wavelength, despite lower peak power and pulse energy settings • for the 1927-nm wavelength, higher power settings can cause greater superficial disruption to the stratum corneum and epidermis with subsequent uptake enhancement1 – the current analysis demonstrates the ability of the 1927-nm wavelength to produce more favorable uptake, especially at the higher power setting • taken together, these results suggest that the 1927-nm wavelength may be used as laser pretreatment to enhance topical delivery, even for relatively hydrophilic topicals presented at the 2021 fall clinical dermatology conference • october 21-24, 2021 • las vegas, nv, and virtual funding information: this study was sponsored by solta medical. medical writing support was provided by medthink scicom and funded by solta medical. disclosures: jvw is an investigator for solta medical. pmf serves on the advisory board and speaker bureau for solta medical. ak and cp are employees of and may hold stock or stock options in solta medical. rgg is an investigator and advisory board member for solta medical. references: 1. friedman et al. j drugs dermatol. 2020;19:s3-s11. 2. ganti and banga. j pharm sci. 2016;105:3324-3332. parameter setting device wavelength, nm 1440 1927 1927 spot density, mtz/cm2 80 80 80 peak power, w 1.2 0.6 1.0 spot size, µm 130 130 130 pulse energy, mj 9.0 4.5 7.5 mtz, microscopic treatment zones. sample & refill 500-µm skin graft topical formulation pbs solution w/ 0.2% sodium azide donor chamber permeation/diffusion chamber stir bar stir rotation 1440 nm (1.2 w) 1927 nm (0.6 w) 1927 nm (1.0 w) control 1.77 ± 0.41 2.65 ± 0.24 4.60 ± 0.80 1440 nm (1.2 w) — 1.50 ± 0.26 2.60 ± 0.61 1927 nm (0.6 w) — — 1.74 ± 0.63 2.63 4.45 7.46 14.48 0 2 4 6 8 10 12 14 16 18 0 5 10 15 20 25 30 time, hours control 1435nm-1.2w-9mj 1927nm-0.6w-4.5mj 1927nm-1.0w-7.5mj control 1440 nm/1.2 w 1927 nm/0.6 w 1927 nm/1.0 w c um ul at iv e pe rm ea ti o n, m g/ cm 2 skin may 2019 volume 3 issue 3 copyright 2018 the national society for cutaneous medicine 208 research letter factors influencing dermatology rank list preferences among successful applicants giselle prado md1, ryan m svoboda md, ms2, alex glazer, md3, aaron s farberg, md4, darrell s rigel, md, ms5 1national society for cutaneous medicine, new york, ny 2department of dermatology, duke university school of medicine, durham, nc 3department of dermatology, university of arizona, tucson, az 4department of dermatology, icahn school of medicine at mount sinai, new york, ny 5ronald o. perelman department of dermatology, nyu school of medicine, new york, ny a recent study has suggested that increasing the number of residency positions would help alleviate the shortage of dermatologists.1 filling these positions would be straightforward using the demand from the existing applicant pool, however choosing the applicants that best “fit” with a program remains a challenge.2 several studies have looked at applicant factors that predict success of matching, but no recent studies have determined the factors that influence how applicants order their rank list. current dermatology residents throughout the u.s. were invited to participate in an anonymous validated 10 question survey. demographic questions included: gender, marital status, and number of dermatology programs applied to, interviewed with, and ranked. respondents were asked to choose the top 5 reasons for ranking a residency program higher or lower on their rank list.3 the first 100 respondents were included in the study. the average number of residency programs applied to was 57.6, the mean number of programs interviewed at was 8.2, and the mean number of programs ranked was 8.5. (table 1) most respondents matched within their top 3 choices on their rank list. table 1: resident respondent characteristics. characteristic percent mean no. programs applied 57.6 mean no. programs interviewed 8.2 mean no. programs ranked 8.5 gender male 48.0 female 51.0 unanswered 1.0 relationship status single 38.0 married/ domestic partnership 61.0 unanswered 1.0 children yes 27.0 no 72.0 unanswered 1.0 matched in top 3 yes 86.0 no 14.0 skin may 2019 volume 3 issue 3 copyright 2018 the national society for cutaneous medicine 209 interestingly, geographic location was the top reason for both ranking programs higher and lower. (table 2) reputation and prestige of the sponsoring institution also influenced higher and lower ranking. other frequently cited reasons for ranking a program higher were: personal experience from prior rotation, perceived quality of current residents, and perceived camaraderie among residents. when ranking a program lower, respondents were typically concerned with: perceived stability of the department, worklife balance, and personal interactions with residents on interview day. factors such as perceived environment for women and minorities, employment benefits, and elective opportunities were not as high a priority. however, in contrast to a previous study4, there were no significant differences in preferences when selections were stratified by gender, marital status, and having children. other specialties have also noted the importance of geographic location among resident rank lists.3 although the overwhelming majority of dermatology residency positions are filled1, nonetheless this information may be valuable to residency program leadership in order to more effectively highlight the strengths of their location. this may include a presentation on local attractions, accessibility, and a description of a typical day in the life of a resident. while some of these factors are fixed, other factors such as the applicant experience on interview day and perceptions of the department could be better optimized. residency programs can maximize applicant perceptions by highlighting the successes and camaraderie of the current resident cohort. for example, the interview day experience could be enhanced by scheduling interviews so there are no long periods of waiting. providing the applicants an opportunity to engage in fun activities with current residents during downtime between interviews may leave applicants with a more positive view of the experience. in turn, the applicants the program attracts will be a better “match” to the program. program directors and chairs may benefit from the findings of this study as they engage in their residency recruitment process. conflict of interest disclosures: none. funding: none. corresponding author: giselle prado, md national society for cutaneous medicine new york, ny drgiselleprado@gmail.com references: 1. jayakumar kl, lipoff jb. trends in the dermatology residency match from 2007 to 2018: implications for the dermatology workforce. j am acad dermatol. 2019;80(3):788-790. 2. national resident matching program. the match, national resident matching program. 2019. http://www.nrmp.org/. 3. auriemma mj, whitehair cl. how prospective physical medicine and rehabilitation trainees rank residency training programs. pm&r. 2018;10(3):286-292. 4. long em, clarke j, sceppa j, miller j. a perfect match: factors involved in dermatology residency applicant’s decision making. j am acad dermatol. 2014;50(3):supplement p83. mailto:drgiselleprado@gmail.com http://www.nrmp.org/ skin may 2019 volume 3 issue 3 copyright 2018 the national society for cutaneous medicine 210 table 2: factors affecting rank list ordered by frequency of selection. position factors that impact higher position % factors that impact lower position % 1 geographic location 55.0 geographic location 53.0 2 personal experience from prior rotation at department 44.0 perceived stability of dermatology department 33.0 3 perceived quality of current residents 39.0 work-life balance 31.0 4 perceived camaraderie among current residents 35.0 personal interactions with current residents on interview day 30.0 5 reputation and prestige of sponsoring institution 32.0 reputation and prestige of sponsoring institution 28.0 6 work-life balance 31.0 perceived quality of clinical facilities 26.0 7 proximity to family 28.0 perceived quality of current residents 23.0 8 perceived quality of didactic curriculum 26.0 size of program 23.0 9 size of program 26.0 call schedule 22.0 10 diversity of patient population 26.0 geographic preference of spouse 7.0 11 personal interactions with current residents on interview day 24.0 impression of program director from interview day 20.0 12 perceived stability of dermatology department 24.0 proximity to family 19.0 13 geographic preference of spouse 19.0 perceived camaraderie among current residents 18.0 14 impression of program director from interview day 17.0 cost of living 18.0 15 perceived quality of clinical facilities 14.0 perceived quality of didactic curriculum 15.0 16 mentor/colleague/ad visor recommendation 11.0 personal experience from prior rotation at department 15.0 17 research opportunities 11.0 diversity of patient population 14.0 18 cost of living 10.0 availability of free meals for residents 13.0 19 placement of recent graduates into desired fellowships 10.0 perceived environment for minorities 11.0 20 call schedule 5.0 elective opportunities offered 10.0 21 elective opportunities offered 3.0 mentor/colleague/ad visor recommendation 10.0 skin may 2019 volume 3 issue 3 copyright 2018 the national society for cutaneous medicine 211 22 program’s willingness to allow & pay for conference attendance 3.0 research opportunities 10.0 23 employment benefits 2.0 perceived environment for women 8.0 24 perceived environment for minorities 2.0 placement of recent graduates into desired fellowships 8.0 25 perceived environment for women 2.0 employment benefits 7.0 26 availability of free meals for residents 0.0 program’s willingness to allow & pay for conference attendance 6.0 skin july 2019 volume 3 issue 4 copyright 2019 the national society for cutaneous medicine 286 compelling comments an exciting, innovative, and compelling dermatology subspecialty worthy of continued consideration among dermatology residents robert t. brodell, md1, tammie ferringer, md2 1department of dermatology, university of mississippi medical center, jackson, ms 2department of pathology, geisinger medical center, danville, pa in 1974, the american board of dermatology and the american board of pathology came together to offer certification for special competence in dermatopathology.1 the first accredited dermatopathology fellowships began in 1976.1 attention was focused on this field which provides a scientific basis for the diagnosis of over 1500 disorders. this political victory led pathologists and dermatologists to agree on a training program which produced excellent dermatopathologists from dermatologytrained and pathology-trained physician pools. it has broken down silos and enriched the specialty. in january 2013, the field of pathology was rocked by a 52% decrease in medicare (center for medicare services-cms) payment for the technical component (88305 code) and a smaller cut in professional fees.2 this led to a number of problems beyond financial exigencies. jobs dried up for new graduates of dermatopathology programs as laboratories froze hiring to help maintain salaries of their physicians and staff. dermatology residents had choices with regard to other subspecialties or general dermatology. this led to a gradual downturn in applications for dermatopathology fellowship positions from dermatologists. though the number of fellowships has declined, pathology residents have continued to apply for dermatopathology fellowships at a strong rate. (see table 1) to paraphrase samuel clemens, “reports of the death of dermatopathology are greatly exaggerated.” in 2018, incomes for dermatopathologists held strong ($431,000† for academic and $480,000†† for private practice).3 furthermore, dermatopathologists love what they do. the attraction that many dermatopathologists find for the field are summarized in table 2. though salaries in dermatopathology remain high, the richness of our field is rooted in much more than monetary gain for the physician. we hope to play a role in increasing the trickle of applicants from clinical dermatology to a flood. this is critical to maintain the diversity that has been a key strength of dermatopathology and insure continued gains in patient care, education and research. † mgma academic total compensation †† mgma private practitioner total compensation skin july 2019 volume 3 issue 4 copyright 2019 the national society for cutaneous medicine 287 table 1: dermatology-trained and pathology-trained fellows (1975-present) year total candidates total abd total abp 1974 204 119 85 1975 177 141 36 1976 111 55 56 1977 123 68 55 1978 123 60 63 1979 116 57 59 1980 117 53 64 1981 125 66 59 1982 108 50 58 1983 60 31 29 1984 55 30 25 1985 35 8 27 1986 27 14 13 1987 29 13 16 1988 26 11 15 1989 26 10 16 1990 28 12 16 1991 44 21 23 1992 no exam given 1993 80 41 39 1994 no exam given 1995 97 39 58 1996 no exam given 1997 110 36 74 1998 55 14 41 1999 58 12 46 2000 66 12 54 2001 61 10 51 2002 87 15 72 2003 80 15 65 2004 84 17 67 skin july 2019 volume 3 issue 4 copyright 2019 the national society for cutaneous medicine 288 2005 93 28 65 2006 99 34 65 2007 88 29 59 2008 87 28 59 2009 95 30 65 2010 104 42 62 2011 91 34 57 2012 96 42 54 2013 91 39 52 2014 86 34 52 2015 75 35 40 2016 85 25 60 2017 70 27 43 totals 3472 1457 2015 skin july 2019 volume 3 issue 4 copyright 2019 the national society for cutaneous medicine 289 table 2: reasons dermatopathologists love their work. 1) visual aspect of dermatopathology: this aligns itself well with clinical dermatology. if you like dermatology, you will love dermatopathology. 2) basic science: many physicians went to medical school because they like “science.” pathology has a clear link to the basic science of our field. 3) peace. the slides do not talk back. we love our patients, but there is serenity engendered by work at a microscope. 4) second opinions for difficult cases. it is comforting to know that help is around the corner (digital dermatopathology or snail mailing slides) when needed without shipping the entire patient to another office for a second opinion. 5) collegial associations: dermatopathologists develop unique relationships (team-based care) with clinical dermatologists, general pathologists, primary care physicians, and specialists. these relationships have social and educational value to the physician. 6) variety…. the spice of life. clinical dermatologists enrich their lives by spending time each day in other pursuits such as dermatopathology. in addition, the dermatopathologist sees the most interesting patients from many clinical dermatologists. 7) teaching opportunities. dermatopathologists establish contacts that lead to teaching opportunities in many venues. 8) less pressure to keep to a schedule. sometimes extra time is required to research the clinical history and literature in complicated dermatopathology cases. this does not result in a waiting room overflowing with restless patients. 9) flexibility. the day’s start and end can be adjusted to optimize biorhythms and re-arranged with little notice to accommodate family and personal needs. 10) minimization of administrative hassles. dermatopathologists do not have patient calls, incomplete medical records, and a pile of prior authorizations for expensive medications waiting to be completed at the end of the day. skin july 2019 volume 3 issue 4 copyright 2019 the national society for cutaneous medicine 290 conflict of interest disclosures: robert t. brodell, m.d., discloses the following potential conflicts of interest: multicenter clinical trials: galderma laboratories, l.p.; novartis principal investigator; and, glaxo smith kline. there are no conflicts of interest related to employment, stock ownership, expert testimony, grants, patents filed, received, pending, or in preparation, or royalties. tammie ferringer, md: none funding: none. corresponding author: robert t. brodell, md and tammie ferringer, md references: 1. bernhardt ms. the history of dermatopathology. jama dermatol. 2013;149(10):1140. doi:10.1001/jamadermatol.2013.5622 2. klipp j. ed. laboratory economics. (7) november 2012: 1. 3. 2018 mgma datadive® provider compensation, based on 2017 data. used with permission from mgma, 104 inverness terrace east, englewood, colorado skin january 2018 volume 2 issue 1 copyright 2018 the national society for cutaneous medicine 69 brief articles persistent cutaneous infection due to mycobacterium immunogenum, a relatively novel species skylelr michelle white md a , katrina n kesterson ms b , michael george wilkerson a a department of dermatology, the university of texas medical branch, galveston, texas b college of medicine, the university of tennessee health science center, memphis, tennessee a 30-year-old female presented to the dermatology clinic for an evaluation of a tender lesion on her right leg that was increasing in size. the lesion was first noted two months ago during a vacation in hawaii. the patient denied any trauma to the area, but stated she swam in the ocean and swimming pools while on vacation. no pruritus, drainage, or bleeding was noted. on physical exam, the patient had a violaceous, indurated nodule on the right anterior distal leg with poorly defined borders, overlying fine white scale, and surrounding erythema (figure 1). the lesion was initally diagnosed as a staphylococcal abscess, but did not improve after taking amoxicillin/clavulanic acid (875 mg /125mg twice daily for 3 days) and applying warm compresses. amoxicillin/clavulanic acid was discontinued, doxycycline (100 mg twice daily for 10 days) was initiated, and the patient was instructed to take twice-weekly dilute bleach baths. twenty-four hours later, the patient returned after developing purulent drainage. on abstract mycobacterium immunogenum is a species of nontuberculous mycobacteria (ntm) that has been recently identified as the cause of cutaneous infections. 1-3 historically, the majority of ntm infections were attributed to contamination of municipal water systems due to inadequate equipment sterilization. many of these organisms have been found to grow in distilled water and display resistance to chlorine, formaldehyde, mercury, and standard disinfectants. 4 in the environment, m. immunogenum has been isolated in swimming pools and adjacent showers. 5 a limited number of cutaneous infections with mycobacterium immunogenum have been reported, and an even smaller number of cases have been reported in immunocompetent individuals. we report a case of a persistent cutaneous infection with m. immunogenum in a previously healthy patient successfully treated with clarithromycin 250 mg twice daily for eight weeks. after treatment, the patient remained free of infection and only a minimal scar remained. case report skin january 2018 volume 2 issue 1 copyright 2018 the national society for cutaneous medicine 70 physical exam, the lesion has developed a necrotic base. a biopsy for tissue culture was obtained. doxycycline therapy was continued and mupirocin 2% ointment twice a day for 7 days was added. tissue culture rapidly grew a mycobacterium species, and matrix assisted laser desorption ionization time-of-flight (maldi-tof) method identified the organism as mycobacterium immunogenum. it was found to be susceptible to amikacin and clarithromycin, resistant to cefozitin, ciprofloxacin, imipenem, minocycline, and trimethoprim/sulfamethoxazole, with intermediate susceptibility for linezolid. subsequently, doxycycline and mupirocin ointment were discontinued and oral clarithromycin (250 mg twice daily) was initiated. the patient was also instructed to apply warm compresses (30 minutes nightly) as the lesion was still not healing after biopsy. after eight weeks of treatment, the patient’s symptoms fully resolved. antibiotics and warm compresses were discontinued after resolution of the lesion (figure 2). eighteen months after initial presentation, the patient denied recurrence of the lesion and only a minimal scar remained. figure 1. a violaceous, indurated nodule on the right anterior distal leg with ill-defined borders. overlying fine white scale and surrounding erythema on initial presentation to the dermatology clinic. skin january 2018 volume 2 issue 1 copyright 2018 the national society for cutaneous medicine 71 figure 2. six weeks after tissue biopsy and one month of treatment with clarithromycin, a level scar with red pigment and slight scale remains. mycobacterium immunogenum (formerly m. immunogen) was first characterized in 2001 as belonging to the mycobacterium chelonae-mycobacterium abscessus group of nontuberculous mycobacteria. it is a rapidly growing aerobic gram-positive, acid and alcohol-fast, non-pigmented bacillus. 1 identification of new ntm species has been possible due to genetic methods. pcrrestriction enzyme analysis patterns of a 439 bp fragment of the hsp65 gene distinguished m. immunogenum from other mycobacterium species. 1,6 although 16s ribosomal dna sequencing shows only an 8 bp difference from m. abscessus and a 10 bp difference from m. chelonae. 6 the maldi-tof spectrometry method used to identify m. immunogenum in this case, utilizes protein fingerprint analysis to identify bacteria and yeast. 7 m. immunogenum has been implicated as the causative agent in several reported skin infections (table 1). these cases were observed after penetrating trauma like tattoo needles, medication injections, and intravenous catheters. 2,4,8 similar to other ntm, m. immunogenum is capable of contaminating hospital water and equipment due to its resistance to a variety of discussion skin january 2018 volume 2 issue 1 copyright 2018 the national society for cutaneous medicine 72 disinfectants, biocides, and its ability to form biofilms. 7 in a one study, m. immunogenum was the second most common ntm isolated from swimming pools. unlike other ntm species, m. immunogenum was not isolated in spas or whirlpools. 5 disseminated infections have also been observed in solid organ and bone marrow transplant patients. the disseminated disease often presents cutaneously with multiple painful skin nodules or draining abscesses. 3,6 table 1. case reports of mycobacterium immunogenum cutaneous infection case reports of mycobacterium immunogenum cutaneous infection year published number of cases patient presentation treatment 2001 1 disseminated cutaneous infection in a patient with scid 1 2001 1 disseminated cutaneous infection in a patient after liver transplant 1 2005 1 immunocompetent patient with chronic ulcer on shin heat compresses; resistant to antibiotics 5 2009 3 cutaneous infections following mesotherapy at the injection site combination of clarithromycin with either ciprofloxacin or levofloxacin for 6-8 months 9 2010 1 healthy patient with nonhealing leg lesion, no prior exposure clarithrimycin and levofloxacin for 9 months 7 2010 1 incision site infection in patient with multiple myeloma on dexamethasone and il-6 inhibitor azithromycin for 5 months 7 2011 1 cutaneous infection in a healthy patient at site of tattoo clarithromycin for 7 months with advice to continue for 9-12 months 2 2017 1 cutaneous infection of lower leg in a healthy patient clarithromycin for 8 weeks with heat compresses cases of cutaneous infections in immunocompetent patients with no known exposure are limited but are similar to the case presented. in 2005, the first reported case of m. immunogenum in an immunocompetent patient was described as a chronic ulcer on the shin. initially, the ulcer was resistant to antibiotic treatment and eventually resolved with heat compresses by the time the causative agent was identified. 9 in 2010, another case of m. immunogenum causing a nonhealing leg lesion in a healthy individual was reported. the patient had no history of exposure, and skin january 2018 volume 2 issue 1 copyright 2018 the national society for cutaneous medicine 73 required extensive treatment with clarithromycin and levofloxacin for 9 months. 10 the best treatment for cutaneous m. immunogenum infection is still not known, and has been based on the susceptibility testing of the tissue culture. clarithromycin has been effective in disseminated and localized infections, however, additional agents are recommended to avoid the development of resistance. 3 although an additional agent should have been considered for this patient, the lesion still reached resolution with monotherapy. the recommended treatment duration for disseminated infection is still unclear, but may last up to 6 months with clarithromycin and up to 4 months with an additional drug. 3 application of mild heat by the use of a warm compress was used in addition to antibiotics in our patient. it is unclear if the application of heat is of benefit in the treatment of m. immunogenum, but it has been shown to be of benefit in the treatment of other ntm infections, such as mycobacterium marinum. 11 the patient presentation demonstrates similarities to the previous cases of m. immunogenum cutaneous infections in immunocompetent hosts. ntm should be considered in cases of non-healing lesions, classically on the extremities, resistant to antibiotics used for treating staphylococcal species. as m. immunogenum displays multi-drug resistance, a tissue culture with species identification should be performed with susceptibility testing to determine appropriate treatment. conflict of interest disclosures: none. funding: none. corresponding author: skyler michelle white, md 301 university blvd., 4.112 mccullough bldg. galveston, tx 77555-0783 409-772-1911 (office) 409-772-1943 (fax) skwhite@utmb.edu references: 1. wilson rw, steingrube va, bottger ec, et al. mycobacterium immunogenum sp. nov., a novel species related to mycobacterium abscessus and associated with clinical disease, pseudo-outbreaks and contaminated metalworking fluids: an international cooperative study on mycobacterial taxonomy. international journal of systematic and evolutionary microbiology. 2001;51(5):1751-1764. 2. mitchell cb, isenstein a, burkhart cn, et al. infection with mycobacterium immunogenum following a tattoo. journal of the american academy of dermatology. 2011;64(5). 3. biggs h, chudgar s, pfeiffer c, et al. disseminated mycobacterium immunogenum infection presenting with septic shock and skin lesions in a renal transplant recipient. transplant infectious disease. 2012;14(4):415-421. 4. wallace rj, brown ba, griffith de. nosocomial outbreaks/pseudo outbreaks caused by nontuberculous mycobacteria. annual review of microbiology. 1998;52(1):453-490. 5. briancesco r, meloni p, semproni m, bonadonna l. non-tuberculous mycobacteria, amoebae and bacterial indicators in skin january 2018 volume 2 issue 1 copyright 2018 the national society for cutaneous medicine 74 swimming pool and spa. microchemical journal. 2014;113:48-52. 6. brown-elliott ba, wallace rj. clinical and taxonomic status of pathogenic nonpigmented or late-pigmenting rapidly growing mycobacteria. clinical microbiology reviews. 2002;15(4):716-746. 7. mareković i, bošnjak z, jakopović m, et al. evaluation of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry in identification of nontuberculous mycobacteria. chemotherapy. 2016;61(4):167-170. 8. del castillo m, palmero d, lopez b, et al. mesotherapy-associated outbreak caused by mycobacterium immunogenum. emerging infectious diseases. 2009;15(2):357-359. 9. loots ma, jong md, soolingen d, et al. chronic leg ulcer caused by mycobacterium immunogenum. journal of travel medicine. 2006;12(6):347-349. 10. shedd ad, edhegard kd, lugo-somolinos a. mycobacterium immunogenum skin infections: two different presentations. international journal of dermatology. 2010;49(8):941-944. 11. collins ch, grange jm, noble wc, yates md. mycobacterium marinum infections in man. journal of hygiene. 1985;94(02):135149. synopsis • psoriasis is a chronic inflammatory skin disease that negatively impacts quality of life, leading to significant physical and emotional burden1 • brodalumab is a fully human interleukin-17 receptor a antagonist approved for the treatment of moderate-to-severe plaque psoriasis in adult patients with inadequate response or loss of response to other systemic therapies2 • treatment interruption is a common real-world experience in individuals with psoriasis3 methods • in a double-blind, placebo-controlled study (nct01708590; amagine-1),4 patients with moderate-to-severe psoriasis were randomized to brodalumab 210 mg or placebo every 2 weeks (q2w) • at week 12, patients receiving brodalumab who achieved a static physician’s global assessment (spga) of 0 or 1 were rerandomized to their induction dose of brodalumab or placebo • beginning at week 16, all rerandomized patients who experienced return of disease (spga ≥3) qualified for retreatment and received an induction dose of brodalumab • efficacy was assessed by observed psoriasis area and severity index (pasi) response • health-related quality of life was evaluated with the dermatology life quality index (dlqi) in the retreatment group (n=79) using nonresponder imputation (nri), stratified by disease response to previous biologic treatment before entering the study (prior biologic failure [n=18]; prior biologic nonfailure [n=61]) results efficacy • a total of 79 patients randomized to brodalumab 210 mg q2w in the induction phase and rerandomized to placebo in the withdrawal phase experienced return of disease (retreatment group) • most patients with psoriasis who experienced a return of disease after brodalumab withdrawal returned to their previous levels of pasi response after 24 weeks of retreatment with brodalumab (figure 1) health-related quality of life • mean (se) dlqi scores in patients in the brodalumab retreatment population at baseline (prior biologic failure, 14.1 [1.9]; prior biologic nonfailure, 12.9 [0.8]) improved at week 52 (prior biologic failure, 1.9 [1.1]; prior biologic nonfailure, 1.8 [0.4]), similar to dlqi scores achieved during the induction phase at week 12 (figure 2a) – change in dlqi from baseline to week 52 for the prior biologic failure and nonfailure subgroups were -11.5 (95% ci, -15.6 to -7.4) and -11.0 (95% ci, -12.8 to -9.2), respectively (figure 2b) – no significant differences in dlqi were observed by prior biologic response through week 52 (p>0.05 between subgroups) figure 1. pasi 75, pasi 90, and pasi 100 rates after 24 weeks of retreatment with brodalumab 210 mg q2w in patients randomized to brodalumab 210 mg q2w in the induction phase and rerandomized to placebo in the withdrawal phase. observed data analysis. n1, number of patients who entered retreatment phase and had a valid measurement value at the specified week while in the retreatment phase; pasi 75, 90, and 100, psoriasis area and severity index 75%, 90%, and 100% improvement; q2w, every 2 weeks. figure 2. (a) mean total dlqi and (b) change in dlqi from baseline to week 52 for patients in the brodalumab retreatment group by response to prior biologic treatment. error bars are (a) se and (b) 95% ci. nonresponder imputation. dlqi, dermatology life quality index. retreatment with brodalumab results in skin clearance and improvements in quality of life in patients with psoriasis after treatment interruption april armstrong,1 brian keegan,2 george han,3 abby jacobson4 1university of southern california, los angeles, ca; 2princeton dermatology associates, monroe, nj; 3department of dermatology at mount sinai beth israel, new york, ny; 4ortho dermatologics (a division of bausch health us, llc), bridgewater, nj objective • to present efficacy and health-related quality of life data after brodalumab withdrawal and retreatment conclusions • reinitiation with brodalumab after treatment withdrawal led to robust levels of skin clearance recapture; patients returned to their previous levels of responses by 24 weeks • improvement in quality of life was maintained after retreatment with brodalumab, regardless of exposure to prior biologic treatment • these results are relevant to real-life practice given that it is relatively common for patients to stop and restart their medications because of various factors funding: this study was sponsored by ortho dermatologics. medical writing support was provided by medthink scicom and funded by ortho dermatologics. ortho dermatologics is a division of bausch health us, llc. author disclosures: aa reports serving as a research investigator and/or scientific advisor for abbvie, boehringer ingelheim, bristol myers squibb, dermavant, dermira, eli lilly, epi, incyte, janssen, leo pharma, novartis, ortho dermatologics, pfizer, sanofi, sun pharmaceutical, regeneron, and ucb. bk reports serving as an investigator, advisory board member, and/or speaker for valeant pharmaceuticals north america llc (currently bausch health us, llc). gh reports serving as an investigator, consultant, advisor, and/or speaker for abbvie, athenex, boehringer ingelheim, bond avillion, bristol myers squibb, celgene, dermtech, eli lilly, genzyme, incyte, janssen, leo pharma, mc2, novartis, ortho dermatologics, pellepharm, pfizer, regeneron, sanofi, sun pharmaceutical, and ucb. aj is an employee of ortho dermatologics (a division of bausch health us, llc). previous presentation information: data included in this poster have been previously presented in part at the 44th annual hawaii dermatology seminar®; february 16-21, 2020; maui, hi. references: 1. aldredge and higham. j dermatolog nurses assoc. 2018;10:189-197. 2. siliq [package insert]. bausch health us, llc; 2017. 3. lebwohl et al. j drugs dermatol. 2020;19:384-387. 4. papp et al. br j dermatol. 2016;175:273-286. presented at fall clinical dermatology conference • october 21-24, 2021 • las vegas, nv, and virtual sponsored by ortho dermatologics, a division of bausch health us, llc. internal use only. not to be copied or used in sales presentations. ortho dermatologics proprietary and confidential 1 1 figure 1 100 100 100 0 20 40 60 80 100 week 24 97 97 100 0 20 40 60 80 100 week 24 84 90 95 0 20 40 60 80 100 week 24 of the patients who achieved pasi 75, pasi 90, and pasi 100 before brodalumab withdrawal, 100%, 97%, and 95%, respectively, reached their prior score after 24 weeks of retreatment with brodalumab patients who achieved pasi 75 at week 12 patients who achieved pasi 90 at week 12 patients who achieved pasi 100 at week 12 pasi 75 pasi 90 pasi 100 n1 = pa tie nt s w ho re ca pt ur ed p a si 7 5, % pa tie nt s w ho re ca pt ur ed p a si 9 0, % pa tie nt s w ho re ca pt ur ed p a si 1 00 , % 32 30 21 n1 = 32 30 21 n1 = 32 30 21 internal use only. not to be copied or used in sales presentations. ortho dermatologics proprietary and confidential 2 figure 2 14.1 1.9 1.9 12.9 1.7 1.8 0 5 10 15 20 baseline week 12 week 52 m ea n to ta l d lq i s co re mean total dlqi biologic failure biologic nonfailure -11.5 -11.0 -20 -15 -10 -5 0 biologic failure biologic nonfailure dl q i c ha ng e fr om b as el in e change in dlqi from baseline to week 52 a b skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 443 brief articles optimizing medical student dermatology education with the american academy of dermatology’s basic dermatology curriculum paul a. regan, bs1, joslyn sciacca kirby, md, med, ms1 1penn state college of medicine, penn state health milton s. hershey medical center, hershey, pa despite dermatologic conditions being among the most common complaints in primary care settings, medical schools dedicate an average of only 16 hours to dermatology education.1 this time is predominantly devoted to didactic lectures during the preclinical years, as clinical dermatology rotations are required by less than 10% of schools. minimal exposure to the field of dermatology leads to residents who lack the confidence to diagnose and treat dermatologic conditions. in a 2009 needs assessment to determine the adequacy of undergraduate dermatology clinical curricula, less than 40% of primary care residents indicated that their medical school curriculum prepared them to diagnose and treat common skin disorders.2 this highlights the importance of efficient and effective dermatology learning experiences for students during their undergraduate medical education, especially during clinical rotations. on a clinical dermatology elective, students typically complete recommended textbook readings along with didactic lectures given by residents or faculty members. adult learners, however, desire the ability to set the pace of their self-directed learning, and each newer generation of medical students is becoming more reliant on technology as an educational resource.3 medical schools and dermatology programs can accommodate these preferences by incorporating the american academy of dermatology’s basic dermatology curriculum into medical student education. the american academy of dermatology (aad) introduced its basic dermatology curriculum to teach the core principles of dermatology in medical education.4 the standardized online curriculum, designed by primary care and dermatology educators, is composed of 42 peer-reviewed modules and 7 instructional videos (table 1). the morphology, clinical evaluation, and treatment of common skin diseases are highlighted using clinical case scenarios, and the learner’s progress is tested at the conclusion of the module. each module can be completed in less than 30 minutes at a learner’s own pace. the modules can also be used as lectures or in small-group settings, and the curriculum offers example schedules for use during clinical rotations. the basic dermatology curriculum can be accessed by creating a free user account through the aad’s website (https://www.aad.org/member/education/resi review introduction https://www.aad.org/member/education/residents/bdc skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 444 dents/bdc). unfortunately, the curriculum was never widely promoted and has been underutilized as a result, with many medical students and educators unaware of its existence.5 several studies have assessed the use of the basic dermatology curriculum by medical students and primary care residents. researchers at ucsf piloted 18 of the modules during the development of the curriculum.6 fifty-one fourth-year medical students completing a two-week dermatology clerkship were assigned specific modules to complete each day. the students’ knowledge acquisition was assessed with preand post-clerkship tests. all 51 students demonstrated statistically significant improvement in test scores, and the mean pre-clerkship score was 74.0% compared to the average post-clerkship score of 89.0% (p < 0.01).6 on the postclerkship survey, 95% of students found the modules easy to navigate, 94% said the material was clear, and 95% said the modules were engaging.6 students ranked the modules and clinic time (over textbook reading and lectures) as the most important aspects of their learning during the rotation. all of the students agreed that the modules increased their confidence in recognizing common skin disorders. mccleskey evaluated the use of the aad modules in 82 primary care learners completing a clinical dermatology rotation.7 the modules were used in place of lectures during the rotation. mean preand postrotation test scores showed statistically significant improvement (60.1% vs. 77.4% (p < 0.01)).7 residents reported the online modules to be engaging (96%), clear (99%), and worth their time (97%), and they preferred the modules to other teaching methods.7 researchers at ut southwestern embedded the aad modules within their medical student internal medicine clerkship.8 the modules were utilized in a large-group, case-based interactive learning session where dermatology faculty reviewed images from the modules. after the clerkship, 98% of students agreed that the session was effective and that they had increased confidence in describing skin findings.8 mcmichael et al. employed an interactive, lecture-based curriculum adapted from the aad modules to teach dermatology concepts to resident physicians in somalia.9 to assess the short-term impact of the curriculum on dermatology knowledge, the residents were given tests before and after the lectures composed of questions directly from the aad modules. the scores showed a mean improvement of 27%.9 although the studies involved small sample sizes without control groups, the results positively support the use of the basic dermatology curriculum in medical education. the studies demonstrate the successful integration of an online, modulebased educational platform into curricula in various fashions (figure 1). the studies showed substantial knowledge acquisition of dermatology material in medical students and primary care residents, and the curriculum received overwhelming support from learners. https://www.aad.org/member/education/residents/bdc skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 445 table 1. list of american academy of dermatology’s basic dermatology curriculum modules and instructional videos. 1. acne and rosacea 25. how to perform a punch biopsy 26. how to perform a scissor biopsy 2. actinic keratosis and squamous cell carcinoma 27. how to perform a shave biopsy 3. adult cutaneous fungal infections 1: dermatophytes 28. how to perform an excisional biopsy 4. adult cutaneous fungal infections 2: yeasts 29. infantile hemangiomas and vascular malformations 5. advanced pediatric bacterial skin infections 30. infestations and bites 6. atopic dermatitis 31. koh exam 7. bacterial skin infections 32. melanoma 8. basal cell carcinoma 33. molluscum contagiosum 9. basic science of the skin 34. morphology 10. benign skin lesions 35. newborn skin disease: birthmarks 11. blisters 36. newborn skin disease: rashes 12. blotches: dark rashes 37. pediatric fungal infections 13. blotches: light rashes 38. petechiae, purpura and vasculitis 14. contact dermatitis 39. psoriasis 15. cryotherapy 40. red scaly rash: the papulosquamous eruption 16. cutaneous hypersensitivity reactions in children 41. stasis dermatitis and leg ulcers 17. dermatologic therapies 42. sun protection 18. dermatosis in pregnancy 43. the red face 19. drug reactions 44. the red leg 20. erythroderma 45. the skin exam 21. evaluation of pigmented lesions 46. total body skin exam 22. genetic skin disorders 47. urticaria 23. hair loss 48. viral exanthems 24. hiv dermatology 49. warts figure 1. examples of ways in which the basic dermatology curriculum can be incorporated into preclinical and clinical medical student education. the basic dermatology curriculum modules are a high-quality resource for educating medical students. the modules offer streamlined, basic information for students as they learn to describe skin lesions and generate diagnostic and treatment plans. dermatology educators should consider introducing the modules to students during their preclinical education and employing the modules during clinical clerkships. the modules can be used as large-group lectures, in small-group activities, or to supplement lectures and direct independent learning. the ideal clinical dermatology clerkship curriculum likely contains elements of didactic lectures, textbook readings, and online modules in addition to the clinical experiences in the hospital and clinic settings. hopefully, awareness of the aad modules will increase as more dermatology programs incorporate them into medical school curricula in some manner. in addition to increasing knowledge and utilization of the curriculum among medical students, the curriculum should be promoted among primary care residents and practicing physicians as well. opportunities to advertise the curriculum, either through social media or at the meetings of professional associations like the acp and aafp, should be explored. in addition, discussion skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 446 dermatology programs may encourage primary care residency program directors at their own institutions to incorporate the modules into their curricula. for practicing internists and pediatricians, cme credit can potentially be offered to increase utilization. improving dermatology education during medical school and among these groups will ultimately lead to better care for patients from dermatologists and primary care physicians alike. conflict of interest disclosures: none funding: none corresponding author: paul a. regan penn state health milton s. hershey medical center 500 university drive hu14 hershey, pa, 17033 tel: (717) 531-6049 fax: (717) 531-4702 email: pregan@pennstatehealth.psu.edu references: 1. mccleskey pe, gilson rt, devillez rl. medical student core curriculum dermatology survey. j am acad dermatol. 2009;61(1):30-5. 2. hansra nk, o’sullivan p, chen cl, berger tg. medical school dermatology curriculum: are we adequately preparing primary care physicians? j am acad dermatol. 2009;61(1):23-9. 3. scaperotti m, gil n, downs i, et al. development and evaluation of a web-based dermatology teaching tool for preclinical medical students. mededportal. 2017;13:10619. 4. american academy of dermatology. basic dermatology curriculum. available from: https://www.aad.org/education/basic-dermcurriculum. [accessed on december 13, 2018]. 5. stratman ej. commentary: exploring more dermatology education for medical students. who, what, where, when, why, and how? j am acad dermatol. 2009;61(1):36-8. 6. cipriano sd, dybbro e, boscardin ck, shinkai k, berger tg. online learning in a dermatology clerkship: piloting the new american academy of dermatology medical student core curriculum. j am acad dermatol. 2013;69(2):267-72. 7. mccleskey pe. clinic teaching made easy: a prospective study of the american academy of dermatology core curriculum in primary care learners. j am acad dermatol. 2013;69(2):273-9. 8. scott bl, barker b, abraham r, wickless hw. integration of dermatology-focused physical diagnosis rounds and case-based learning within the internal medicine medical student clerkship. j med educ curric dev. 2016;3:105-7. 9. mcmichael jr, thompson kb, kent sc, stoff bk. an intensive modular dermatology curriculum for family medicine residents in a resource-limited setting. int j dermatol. 2018;57(1):119-120. mailto:pregan@pennstatehealth.psu.edu skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 538 brief article idiopathic aseptic facial granuloma caroline garraway, md1, thy huynh, md1,2, robert t. brodell, md, faad1, vinayak k. nahar, md, phd1,3 1 department of dermatology, school of medicine, university of mississippi medical center, jackson, ms 2 dermatology program, boston children's hospital, boston, ma 3 department of preventive medicine, school of medicine, university of mississippi medical center, jackson, ms idiopathic facial aseptic granuloma (ifag) or pyodermite froide du visage is seen exclusively in children.1 it presents as an erythematous to violaceous nodule or plaque most commonly seen on the checks or eyelids.2 this condition most often presents as a single lesion within a triangle-shaped area delineated by the external limit of the orbit, the labial angle, and the ear lobe.6 multiple lesions have also been reported.7 lesions tend to resolve spontaneously with minimal scarring within a few months to a year.2 there are no risk factors that predispose an individual to developing ifag.4 a 14-year-old healthy male presented for evaluation of an asymptomatic, slowly enlarging red lesion following mild eruption of acne. examination revealed a 4 x 4 cm nontender, edematous, firm plaque on the left cheek (figure 1). several acneiform papules were present after 4 months of treatment with oral doxycycline 100 mg daily and topical clindamycin 1% solution. no lymphadenopathy was present. the patient denied any pain, drainage, fever, weight loss or other constitutional symptoms. there was no history of facial redness or blepharitis. a punch biopsy was performed on the left cheek and demonstrated pan-dermal lymphoplasmacytic infiltrate with numerous histiocytes and hemosiderin deposition. a diagnosis of ifag was made. treatment was initiated with oral 13-cis-retinoic acid 40 mg twice daily, oral azithromycin 250 mg daily for 6 days, and topical clindamycin 1% solution. 1 cc of intralesional triamcinolone (10 mg/cc) was injected every other month for 12 months. at 2 month follow up, he was started on a 30-day course of oral amoxicillinclavulanate 875-125 mg twice abstract pyodermite froide du visage, otherwise known as idiopathic facial aseptic granuloma (ifag), is a benign lesion exclusively seen in children and presents as a cold abscess on the face.1 we report a case of a 14-year-old male with ifag who failed initial treatment with oral doxycycline, but responded to treatment with oral 13-cis-retinoic acid, oral amoxicillin-clavulanate and intralesional triamcinolone injections over a 7 month period. introduction case report skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 539 figure 1. following four-months of moderate acne vulgaris on the cheeks treated with doxycycline 100 mg daily, the patient developed this erythematous, indurated, multi-lobular plaque on the left cheek typical of idiopathic facial aseptic granuloma. daily with imperceptible clinical changes. improvement was finally noted after four intralesional triamcinolone injections and seven months of oral 13-cis-retinoic acid 40 mg twice daily (figure 2). continued improvement was noted after restarting doxycycline 100 mg daily, and six intralesional triamcinolone injections (figure 3). two theories have been promulgated to explain the pathogenesis of ifag. it may represent an embryologic remnant of an epidermal cyst resulting in an inflammatory figure 2. following treatment with 13-cis-retinoic acid 40 mg twice daily for 4 months, azithromycin 200 mg pak of 6 tablets monthly for 3 months, and 1 cc of intralesional triamcinolone (10 mg/cc) injected twice two months apart, only modest improvement was noted. reaction or represent localized granulomatous rosacea in childhood.3 patients with ifag are at increased risk for the development of rosacea, especially the ocular variant.2 furthermore, signs of rosacea including flushing, papules, and pustules appear in some patients and both conditions respond slowly to local and systemic antibiotics.2 the differential diagnosis for ifag includes any condition that presents as a “cold” inflammatory nodule or plaque. (see table 1). the medical history and the clinical manifestations of ifag are distinctive, and histopathology can provide evidence to exclude many of these considerations. although this patient did not exhibit a personal history or clinical features of rosacea, treatment approaches mirror those of granulomatous rosacea. after failing to respond to topical and systemic antibiotics, discussion skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 540 figure 3. after one year of treatment including a seven-month course of 13-cis-retinoic acid 40 mg bid followed by doxycycline 100 mg daily, and 6 intralesional injections of 1 cc intralesional triamcinolone (10 mg/cc) every other month, considerable improvement is noted. alternative oral antibiotics were chosen in combination with oral 13-cist-retinoic acid and intralesional steroids.6 it has been shown that 13-cis-retinoic acid can be used safely in the pediatric population.5 it is important to prepare patients and their families for the possibility of prolonged treatment, though the prognosis is excellent in time.4 table 1. conditions that can appear as solitary plaques on the face with distinguishing features condition distinguishing clinical features pilomatrixoma hard or “calcified” nodule. granuloma faciale moist friable, soft, purple-red papule or plaque localized infectious pyoderma red, warm nodule with pus (furuncle) or multiple foci with pus (carbuncle). obtain bacterial culture and sensitivity nodulocystic acne multiple papular, pustular, and nodulo-cystic lesions with comedones scattered over face rosai dorfman disease multiple papules and plaques (not solitary) with lymphadenopathy lymphocytoma cutis homogenous erythema over a nodule with pathology demonstrating a dense lymphocytic infiltrate rather than a granulomatous process exaggerated insect bite reaction fixed urticarial lesion with a history of a bite and many eosinophils in histopathology cutaneous leishmaniasis history of travel, a bite, and ulcerating lesions kerion (inflammatory tinea) history of exposure to soil or an animal with scaling or hair loss (source of zoophilic or geophilic fungus). confirmation with potassium hydroxide (koh) preparation or fungal culture. conflict of interest disclosures: robert t. brodell has participated in multi-center clinical trials with: skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 541 corevitas (formerly corrona) psoriasis registry and novartis. he is also associate editor of the journal of the american academy of dermatology, faculty advisor for the american medical student research journal, and editor-in-chief of practice update: dermatology and serves as staff dermatologist at the gv (sonny) montgomery va hospital in jackson, ms. he is also associate editor of the journal of the american academy of dermatology and editor-in-chief of practice update: dermatology. caroline garraway, thy huynh, and vinayak k. nahar have no conflicts to report. funding: none corresponding author: vinayak k. nahar, md, phd, ms department of dermatology school of medicine university of mississippi medical center 2500 north state street – l216 jackson, ms 39216 usa email: naharvinayak@gmail.com references: 1. roul s, léauté-labrèze c, boralevi f et al. idiopathic aseptic facial granuloma (pyodermite froide du visage): a pediatric entity? arch dermatol 2001;137:1253-1255. 2. miconi f, principi n, cassiani l, et al. a cheek nodule in a child: be aware of idiopathic facial aseptic granuloma and its differential diagnosis. int j environ res public health. 2019;16(14):2471. published 2019 jul 11. doi:10.3390/ijerph16142471 3. orion c, sfecci a, tisseau l, darrieux l, safa g. idiopathic facial aseptic granuloma in a 13-year-old boy dramatically improved with oral doxycycline and topical metronidazole: evidence for a link with childhood rosacea. case rep. dermatol. 2016;8:197201. doi:10.1159/000447624. 4. boralevi f, léauté c, lepreus s et al. idiopathic facial aseptic granuloma: a multicenter prospective study of 30 cases. br j dermatol 2007;156:705-708 5. lee, g. and fischer, g. (2020), isotretinoin therapy for idiopathic aseptic facial granuloma. australas j dermatol. doi:10.1111/ajd.13257 6. neri i, raone b, dondi a et al. should idiopathic facial aseptic granuloma be considered granulomatous rosacea? report of three pediatric cases. pediatr. dermatol. 2013;30:109-11. 7.satta, r., montesu, m.a., biondi, g. and lissia, a. (2016), idiopathic facial aseptic granuloma: case report and literature review. int j dermatol, 55: 13811387. doi:10.1111/ijd.13161 patient tolerability of tazarotene foam, 0.1%, and impact on patient compliance a phase 1 open-label multicenter study to evaluate the safety, tolerability, pharmacodynamics, and pharmacokinetics of calcipotriene foam, 0.005%, applied under maximal-use conditions in adolescent subjects with plaque psoriasis adelaide a. hebert, md, the uthealth mcgovern medical school-houston, houston, texas; debbie glaab msn, cpnp-ac; rhonda schreiber bscn, ms topical application of calciptrione foam, 0.005%, on up to 56% bsa with a median of 22% bsa (including 100% scalp) in adolescent subjects with plaque psoriasis, showed no adverse effect on calcium metabolism. the lack of effect on pd markers of calcium metabolism is consistent with non-quantifiable concentrations in all subjects and confirms that there is no clinically relevant systemic exposure under maximal use conditions. the data presented here demonstrates that this therapy is safe, without evidence of systemic exposure or systemic effects on calcium metabolism, when utilized in adolescent patients with moderate plaque psoriasis. the low incidence of adverse events, lack of discontinuation, and high compliance rates demonstrate that calcipotriene foam, 0.005%, was also well tolerated in this adolescent group. this may lead to additional options in this patient population, which currently has limited treatment alternatives. • phase 1 multicenter, open-label, repeat-dose safety, tolerability, and pkpd study in adolescent subjects with moderate plaque psoriasis (defined as a score of 3 on the investigator’s static global assessment [isga]) involving a minimum of 10% body surface area (bsa) excluding face and scalp, and a minimum of 20% scalp involvement • subjects were instructed to apply calcipotriene foam as a thin layer twice a day for 14 days and once on day 15 on all treatment areas (excluding the face). • average daily dose was 5.04g • blood samples for albumin adjusted calcium, intact parathyroid hormone (ipth), alkaline phosphatase, magnesium, and phosphorus were scheduled to be collected at screening, on day 1 (before the first dose), on day 15 (3 to 9 hours after dosing), and on day 22 if the results from day 15 showed any abnormalities • serum 25-oh vitamin d concentrations were evaluated on day 1 (before the first dose) • safety and tolerability were evaluated throughout the treatment period and a 7-day follow-up period • urine samples for evaluation of calcium/creatinine ratio were collected before dosing on days 1 and 15 , conclusions methods results psoriasis is a chronic immune-mediated inflammatory skin disorder with significant physical and psychosocial ramifications which begins in childhood in almost one-third of cases.2,3 the etiology of plaque psoriasis in children and adults is thought to be the same, as evidenced by similar response rates to therapies.2 however, pediatric treatment guidelines are limited and most therapies are not approved in this patient population.4 additionally, the pharmacokinetics (pk) and pharmacodynamics (pd) of drugs and certain factors that are unique to children such as metabolism, physical development and cutaneous absorption make safe and effective treatment of psoriasis in this patient population a challenge.5 phase iii clinical trials established the efficacy and safety of calcipotriene foam, 0.005%, in adults. while subjects under the age of 18 were included in these trials, there were not sufficient numbers to fully evaluate the safety and efficacy in this age group. for this reason, two subsequent studies were initiated in patients 4 to 11 years and 12 to 16 years. the data presented here highlight the results of the phase i clinical study in the adolescent group. synopsis to evaluate the safety and tolerability of calcipotriene foam, 0.005%, in subjects 12 to 16 years of age with plaque psoriasis via analysis of calcium metabolism and to evaluate whether these changes were related to the average dose administered, age, body surface area (bsa), bsa treated, and/or %bsa treated. primary endpoints: • the relative change from day 1 to day 15 (day 15/day 1 ratio) of albumin adjusted serum calcium, intact parathyroid hormone (ipth), alkaline phosphatase, magnesium, and phosphorus • change in urine calcium/creatinine from day 1 to day 15 secondary endpoints: • safety: adverse events, clinical laboratory test results, vital signs, concomitant medications • tolerability: investigator assessment of erythema, subject assessment of pain • pharmacokinetics: plasma concentrations of calcipotriene objective there were no quantifiable changes in serum labs. while urine ca/cr and serum ipth were highly variable there were no significant trends apparent. no relationships between covariates and markers of calcium metabolism were seen. no relationship was seen between pd markers for calcium metabolism and the covariates average dose, age, bsa, bsa treated and/or %bsa treated. there were 5 adverse events considered related to treatment and no serious adverse events, deaths or adverse events leading to permanent discontinuation of study drug or withdrawal from study. compliance with treatment regimen was high in study subjects at approximately 92%. pd marker visit (n) mean min max corrected calcium (mmol/l) screening (19) 2.31 2.2 2.42 day 1 (19) 2.30 2.16 2.42 day 15 (19) 2.29 2.18 2.4 day 22 (7)* 2.30 2.14 2.42 ipth (pmol/l) screening (19) 3.93 1.1 8.3 day 1 (19) 4.14 1.6 8.8 day 15 (19) 3.74 1.2 7.9 day 22 (7)* 3.73 2.1 6.3 alkaline phosphatase (µ/l) screening (19) 172.8 66 553 day 1 (19) 172.6 79 600 day 15 (19) 173.0 62 621 day 22 (7)* 146.9 63 282 magnesium (mmol/l) screening (19) 0.83 0.76 0.9 day 1 (19) 0.83 0.76 0.96 day 15 (19) 0.81 0.7 0.9 day 22 (7)* 0.84 0.8 0.9 phosphorus (mmol/l) screening (19) 1.38 1.1 1.95 day 1 (19) 1.38 0.85 1.85 day 15 (19) 1.31 0.7 2.05 day 22 (7)* 1.25 0.85 1.55 pd marker at screening, day 1, day 15 and day 22 *serum labs were repeated at day 22 if the results from day 15 showed any abnormality relative change from day 1 to day 15 for urine calcium/creatinine ratio pd marker visit ratio (n) geometric mean calcium : creatinine (mmol/mol cr) day 15 : day 1 1.2731 demographics n (%) demographics n (%) age (years) mean 12-13 14-16 14.4 5 (26%) 14 (74%) weight (kg) mean minimum maximum 74.1 47.0 129.3 race caucasian african american asian other 12 (63%) 4 (21%) 2 (11%) 1 (5%) baseline isga mean body mean scalp 3.0 2.8 gender male female 9 (47%) 10 (53%) total bsa (%) mean minimum maximum 1.3 1 1.8 ethnicity hispanic/latino not hispanic/latino 6 (32%) 13 (68%) time since diagnosis (yrs) mean 4.3 dr. hebert received research funding for this study. all funding was paid to the uthealth mcgovern medical school-houston, houston, texas. ms. glaab and ms. schreiber employed by mayne pharma. this study, analysis, and presentation was sponsored by mayne pharma. this study, analysis, and presentation were sponsored by mayne pharma. affiliations 1. tollefson mm, crowson cs, mcevoy mt, et al. incidence of psoriasis in children: a population-based study. j am acad dermatol. 2010;62(6):979-87. 2. kimball ab, gold mh, zib b, et al. clobetasol propionate emulsion formulation foam phase iii clinical study group. clobetasol propionate emulsion formulation foam 0.05%: review of phase ii open-label and phase iii randomized controlled trials in steroid-responsive dermatoses in adults and adolescents. j am acad dermatol. 2008;59(3):448-54. 3. bronckers imgj, palle as, et al. psoriasis in children and adolescents: diagnosis, management and comorbidities. 4. paediatr drugs. 2015 oct;17(5):373-84. 5. de moll eh, chang mw, strober b. psoriasis in adults and children: kids are not just little people. clin dermatol. 2016 nov dec;34(6):717-723. 6. thomas j, parimalam k. treating pediatric plaque psoriasis: challenges and solutions. pediatric health, medicine and therapeutics 2016 april;21(7):25-38. 7. data on file. greenville, nc; mayne pharma, llc. references pd marker visit ratios n geometric mean 95% ci 90% ci corrected calcium (mmol/l) day 15/day 1 ratio 19 0.9970 0.9861 1.0079 0.9880 1.0060 day 22/day 1 ratio 7 0.9849 0.9533 1.0176 0.9597 1.0108 day 15/day 22 ratio 7 1.0091 0.9776 1.0417 0.9840 1.0349 ipth (pmol/l) day 15/day 1 ratio 17 0.8546 0.6375 1.1455 0.6714 1.0878 day 22/day 1 ratio 7 1.0491 0.6436 1.7101 0.7117 1.5465 day 15/day 22 ratio 6 0.8257 0.4017 1.6969 0.4694 1.4523 alkaline phosphatase (u/l) day 15/day 1 ratio 19 0.9793 0.9282 1.0332 0.9369 1.0235 day 22/day 1 ratio 7 0.9585 0.8480 1.0835 0.8696 1.0565 day 15/day 22 ratio 7 1.0038 0.9361 1.0763 0.9497 1.0609 magnesium (mmol/l) day 15/day 1 ratio 19 0.9770 0.9383 1.0173 0.9450 1.0101 day 22/day 1 ratio 7 1.0085 0.9684 1.0502 0.9765 1.0415 day 15/day 22 ratio 7 1.0000 0.9554 1.0467 0.9644 1.0369 phosphorus (mmol/l) day 15/day 1 ratio 19 0.9372 0.8389 1.0469 0.8553 1.0269 day 22/day 1 ratio 7 0.9440 0.8680 1.0266 0.8831 – 1.0090 day 15/day 22 ratio 7 0.9812 0.7350 1.3099 0.7800 1.2343 ae type n (%) # of events overall 3 (16%) 5 general disorders and administration site conditions 2 (11%) 4 application site pain 1 (5.3%) 2 application site pruritus 2 (11%) 2 skin and subcutaneous tissue disorders 1 (5.3%) 1 pruritus 1 (5.3%) 1 relative change from day 1 to day 15 and day 22 for pd markers relative change from day 1 to day 15 and day 22 for pd markers *no serious aes or deaths https://www.ncbi.nlm.nih.gov/pubmed/?term=the+physical+and+psychosocial+ramifications+of+psoriasis+in+school+age+children+and+adolescents+are+significant skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 322 compelling comments finding a sense of gratitude and purpose in medicine through positive role models and a diversity of passions, experiences, and practices haley d. heibel, md1, clay j. cockerell, md, mba1,2, christina guillen, md3, oluwatoyin bamgbola, md3, john schmidt, md4, poonam sharma, mbbs5, robert white, md6, susan youens, phd7, mark d. heibel, md8 1cockerell dermatopathology, dallas, tx 2departments of dermatology and pathology, ut southwestern medical center, dallas, tx 3department of pediatrics, suny downstate health sciences university, brooklyn, ny 4department of pediatrics, creighton university school of medicine, omaha, ne 5department of pathology, creighton university school of medicine, omaha, ne 6beacon children’s hospital, south bend, in 7department of music, university of notre dame, notre dame, in 8heibel dermatology clinic, lincoln, ne when i1 was younger, i thought that people who had achieved their dreams had done so heroically on their own and carried a special set of talents to do so. however, in my life 1 i is in reference to the first author in this essay, haley d. heibel, except when denoted by each individual author’s response throughout the manuscript. experiences i’ve learned that many great accomplishments often come with collaboration, sharing of ideas, and support from others. i have been very fortunate to meet inspirational people in my education and medical training, who helped me realize and develop the gifts and talents i have to offer others. they encouraged me to reach my potential, develop ideas, and achieve accomplishments that i would not have been capable of without their support. abstract as burnout is an issue facing our profession, developing and nurturing a greater purpose which promotes a sense of gratitude and meaning in medicine is important for physician wellness and resilience. we often develop our sense of purpose through the internalization of values and ideas of people we have met in life. mentors play an important role in helping us realize and develop our skills and talents, which may not have been readily apparent to us. in this essay, i, as a physician pursuing dermatology, describe my experiences and what i’ve learned from inspirational teachers and mentors in my education and training that helped me realize the gifts and talents i have to offer the world as a dermatologist. then, my mentors describe how a specific experience or hobby has helped them develop a greater sense of purpose and gratitude in their careers. these are a few of the infinite possibilities which can nurture a sense of gratitude and purpose in our lives, and our goal is for others to reflect on and to expand on these possibilities and share them with colleagues. introduction skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 323 in this essay, i share some of the valuable lessons i have learned from inspirational teachers and mentors that i’ve met at various stages in my life. then, each of them describes how a practice, a project, and/or an experience they have been involved in has led to a greater sense of gratitude and purpose in their career. this essay begins with my experiences in medical residency and research and then continues in reverse chronological order. we hope that this will encourage others to reflect on and appreciate the positive mentoring relationships in their lives and to consider how they may use these experiences in a creative way to help others. by sharing our stories, we hope to cultivate a sense of purpose and gratitude in the practice of medicine, to promote physician well-being, and to prevent burnout. research dr. clay cockerell has been an inspirational mentor for me, and his papers, “pressure and disenchantment in physicians–part i: developing an approach to reconnect with what is noble about medicine”1 and “pressure and disenchantment in physicians–part ii: lessons for physicians from the tao te ching”2 have influenced me to write this current paper. dr. cockerell is a dermatologist and dermatopathologist in dallas, texas, and owner of cockerell dermatopathology laboratories. service to others has been an important part of his career through teaching several students and residents. he also became an expert in hiv dermatology through reading about and helping this patient population when the pandemic affected new york city during his residency training. he later formed an hiv dermatology clinic for these patients when there was a great need. dr. clay j. cockerell’s response on how being involved in hiv dermatology has nurtured a greater sense of purpose and gratitude in his career: when i was a resident and fellow at new york university in the 1980s, we witnessed the advent of the hiv pandemic firsthand. the census of patients at bellevue hospital with hiv infection (the cause of which was not known at the time) went from zero to over 50% of the hospital beds in a matter of months. many patients had skin disorders and, in many cases, skin conditions were the first manifestation of their disease. when i moved to dallas in 1988, there were many patients in the community and in parkland hospital with similar conditions, but there was no coordinated effort to take care of them. as such, i founded an hiv-associated skin disorders clinic where we saw many patients over a number of years and were able to better care for them as well as to gather information that led us to make important observations about those conditions. this was a charity clinic that provided us the opportunity to serve our community as well as these individuals. fortunately, as better treatments emerged, the number of skin problems these patients faced diminished as did the need for the clinic. this was a very gratifying experience for many fellows and others who rotated with us in the clinic as well as for me personally. internship community advocacy dr. christina guillen was my program director during my internship in pediatrics at suny downstate health sciences university. dr. guillen developed and taught a curriculum called, “residents as teachers,” and gave us a skill set to make discussion skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 324 the medical students feel valued as members of the team and to nurture their growth. she was also a strong proponent for community advocacy and made resident wellness a priority. when the covid-19 pandemic hit our hospitals, she demonstrated great strength and calmness as we experienced many challenges and adjusted to many changes in our program structure. she supported us, regularly thanked us, and told us how proud of us she was. dr. guillen: what is a community advocate, and how does being involved in community advocacy give you a sense of gratitude and a greater sense of purpose in your profession? a community advocate is a person who has a vested interest in bringing a positive change that benefits a community. this “vested interest” can be sparked in many forms and by many experiences, but it is the personal experiences that spark the fire and passion to do the work that will improve the lives of others. as a young child, i fondly remember traveling to the dominican republic every summer with my parents to visit my family. preparing for these trips involved filling many boxes with much needed resources that would be sent to organizations that provided aid to people in need. this was the first time in my life that i saw the impact that health disparities had on communities. i would often visit these organizations with my family and meet the people that were doing the outreach work and listen to them discuss the various issues that were affecting the people they served. what was most inspiring was seeing the passion that they had in creating projects and programs that improved the lives of people, especially that of children in their communities. these experiences sparked my interest in advocacy, and it gave me a sense of gratification. my mother often said, “when one is fortunate to have blessings in their lives, it is their duty to pass those blessings along to others in order to make their lives better, and they in turn will do the same.” this to me is the “vested interest” that i have in community advocacy work. while growing up in new york city, i would often spend weekends with my aunt who was a nurse participating in countless community advocacy and outreach projects that ranged from speaking to local politicians about safe housing conditions to participating in neighborhood health fairs. i have always been amazed by her energy and commitment, but it was her passion that continually resonated with me. my career choice as a pediatrician has allowed me to expand on my humble life lessons to a greater cause through advocacy. one of the roles of a pediatrician is to be an advocate for our patients, families, and the community they live in. i want my residents to know the power that they have as advocates, and with this power the positive changes that they can foster. understanding that being an advocate for your patient is sometimes as important as caring for their medical needs and that, in order to improve a child’s health, you must improve the community that they live in. suny downstate health sciences university is located in brooklyn, new york, it serves an underserved and diverse immigrant patient population that is affected by health disparities. through community advocacy and outreach, i know that i can make significant changes that will improve the lives of generations of children to come, and there is no greater sense of purpose as a doctor than this. skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 325 building trusting relationships with patients and their families i met dr. oluwatoyin bamgbola during my pediatric nephrology rotation. prior to this, i had met some of his patients on the inpatient pediatric floors that were admitted under the pediatric nephrology service. i recognized how much his patients trusted his care because the patients would reference things that dr. bamgbola had said in clinic to them prior to admission and believed wholeheartedly in the recommendations that dr. bamgbola had given them. then, i attended clinic with dr. bamgbola. he would give me a comprehensive narrative of the patient’s story and medical condition that was so descriptive prior to the patient coming into the room. i was amazed at how much he remembered about his patients. as a result, i retained and learned so much from each patient experience. he treated each patient like a family member, and he had known some of his patients for several years. it seemed that his patients wanted to stay in his care forever, even when they were moving into their adult years. he provided comprehensive care and took his time to meticulously provide the best care to his patients. he told me that his motivation was, “to make a difference in people’s lives.” it seemed that he truly saw medicine as a calling. dr. oluwatoyin bamgbola’s response on being a clinician as a teacher of life experiences: early life experience has a strong influence not only in my decision to become a physician, but it is also a major determinant of my professional behavior. as a private practitioner in an urban african city, my family physician had a unique ability to attract a waiting room full of patients. at the expense of their comfort, dozens of patients would rather have him attend to their needs than seeing another physician who might possess a better academic qualification. he served as a role model for me in the cultivation of attributes that i consider necessary for an effective clinical practice: empathy, patience, listening skills, cultural regards, and boundary. he spent quality time with every patient, treating them with compassion, respect, and dignity. he worked very hard but was full of fun, making every minute spent in the waiting room worthwhile. he exuded a powerful aura that made me feel he was more than just a physician as he could easily pass for an uncle. in regular conversation, my daddy would refer to him as a friend many more times than calling him a doctor. his attitude to patient care epitomized humanism as a fundamental ingredient of clinical effectiveness. not surprisingly, all his 3 children became physicians, taking over his job after his demise. in the course of my medical training, i easily identified the physicians in the mode of my family doctor. they are result-oriented and are exceptionally successful in their chosen career. i have grown over the years to share in the same professional values. i see each patient as an opportunity to sow a seed, a seed of life that only germinates with the provision of empathy and altruism. i see all of their parents as partners. i listen to them to gain insight of their knowledge (or misunderstanding), synthesize the information to reach a diagnosis, and consciously empower them with skills to tackle the future encounter. i create a friendly atmosphere that encourages patients and their caregivers to relate their stories. if a sibling is around, i do not ignore them. in a non-threatening skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 326 manner, i seek information on his/ her relationship with the patient. we talk about sports, schoolteachers, academics, and close friends. i inquire concerning the health of the parents, not necessarily to reach a diagnosis, but as an opportunity to relate with the family holistically. by so doing, i can create an image that is larger than just being a doctor; i become a part of their home. the major impediment is time, many physicians will say. however, i’ve learned over the years that by building a trusting relationship with the family on the first visit, i can spend less time on follow-up care without arousing animosity. drawing from my own life experience: unpleasant clinical events, medical training in a resource-depleted environment, and being the father of two autistic kids, i have learned to use lessons of my unfulfilled expectations of medical care for the perfection of my approach to clinical services. my life scenario and its moral responsibility have provided me with an avenue for a spiritual awakening. it authenticates my role as an academic physician and at the same time validates my duty as a caring parent. in the hope of cultivating an exemplary professional identity for my students, i have used the same humanistic principle as an effective tool in the teaching of clinical skills. i frequently tapped into my past years of experience to provide stories of relevant clinical encounters. creating such impressionistic images provides an opportunity for an exchange of decisionmaking skills. more importantly, it creates an enduring memory bank that serves as a template for effective experiential learning and a reinforcement of reflective practice. medical school leadership education dr. john schmidt taught a longitudinal course in my medical school education called, “the art and science of leadership,” and he was also the clerkship director for my pediatrics rotation as well as an attending physician in the neonatal intensive care unit. i really enjoyed the leadership course because it made clear to me that the humanistic side of medicine is as important as being competent in the basic sciences. i also realized from an early point in my medical education the importance of using my leadership position and power as a physician in a positive way in the medical team to provide good patient outcomes and to advocate for patients’ needs and for the greater good of society. dr. john schmidt’s response on how teaching leadership to students provides a greater sense of purpose and gratitude in his profession: the actual process of caring for patients and achieving outcomes always seemed to be addressed as simply making the correct diagnosis and using evidence-based medicine to formulate the best plan of care. as a medical student and physician in training, it was rare that anyone ever addressed the breakdown of the process of achieving outcomes. breakdowns occur due to a myriad of factors, such as groupthink, the potential negative effects of holding a position of power, the inherent stresses involved in high-stakes situations, or due to how the “environment” in which you work and inadvertently maintain has huge impacts upon the kinds of outcomes that occur. these leadership issues were rarely a part of my training, and even more rare (non-existent even) was any conversation about the impact that witnessing life in all of its intricacies has on us as individuals. we never discussed the skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 327 moral imagination of our field, and how this influences our state of being as we go about grinding through our jobs and lives. collaborating with colleagues in the leadership science field and reflecting upon the influences of my institution’s mission/philosophy/teachings, i sought to choose to be purposeful in teaching leadership to medical students in a way that was not about boosting one’s cv or about becoming more efficient using management tricks to get people to do what you want. instead, i wanted to have a conversation first and foremost about why we do what we do (why do we care about achieving good outcomes) and couple this with an understanding of and have a discussion about our blind spots, our susceptibilities to getting caught up in power and prestige, our insecurities, our medical culture, etc., etc., and how all of these things impact our ability to achieve good outcomes for our patients. additionally, we discuss our personal ability to maintain a sense of purpose and fulfillment with being a physician. the adequacy of my ability to “teach leadership” is certainly tested daily when interacting with students. even the adequacy of my ability to practice what i preach is frustratingly difficult at times and evokes feeling like an imposter. yet, i find a lot of fulfillment and am grateful for the opportunity to challenge ourselves (our field) to be mindful and purposeful with the time that we have together. reading for leisure dr. poonam sharma is the chair and a professor in the department of pathology at creighton university. dr. sharma encouraged me to do reading outside of medicine and gave me a book to read during my rotation. i hadn’t realized it, but before she had given me this book, my time spent for reading outside of medicine had dwindled. having this book to read as an assignment was refreshing, and it made me feel good to read something that contributed to my personal growth. the book she gave me to read in the rotation has influenced my approach to life and medicine in an important way, and it’s made me a braver person. as someone who had changed career paths, she also taught me the importance of listening to my inner voice, following where my dreams led me, and how to negotiate with others. dr. poonam sharma’s response on how reading non-medical literature and sharing books with her students provides a greater sense of purpose and promotes gratitude in her career: practicing medicine affords us the great privilege of helping others, saving lives, and pursuing an impactful career. medical school is intense and rigorous. the lives of medical students are overwhelmingly absorbed by medical training. their stamina and determination are tested repeatedly, leaving many students feeling disillusioned and completely exhausted. reading as a leisurely activity brings a new perspective and an immediate connection to the world outside medicine. simply opening a book is an invitation to an excursion that distracts us from daily stressors. a library of wellselected books offers opportunity for intellectual growth in areas that are not typically taught in medical school, but are a necessary component of becoming a competent, confident, and compassionate physician. mental stimulation from recreational reading helps improve focus, memory, critical reasoning skills and overall well-being. there is a positive correlation between the amount of academic achievement and the amount of recreational reading. physician burnout is a pervasive problem that appears to be getting worse.3 skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 328 reading is an incredibly inexpensive hobby that provides an excellent resource for building resilience in medical school and life thereafter. a research study conducted by cognitive neuropsychologist, dr. david lewis, revealed that reading for just 6 minutes can reduce stress by up to 68%, compared to performing other activities such as listening to music (stress levels reduced by 61%), or taking a walk (stress levels reduced by 42%).4 this is because reading leads to intense concentration on the present moment, distractions and stresses are eliminated from consciousness, allowing us to enter a “flow” state in which awareness is focused on the here and now. reading nonmedical literature on a regular basis is associated with a significantly decreased likelihood of burnout in the medical profession.5 getting lost in leisurely reading (compared to “hastily drinking water from a firehose” during medical training) is the ultimate joy. it is a source of personal pleasure to be able to encourage students to rekindle and cultivate a love of reading non-medical books in order to broaden their perspective, redirect their focus, and reduce stress. it doesn't matter what book you read, by immersing yourself in a book, you can shun worries of the day and delve into the author's imagination. so, go ahead and indulge in a (non-medical) book of interest for you! undergraduate studies advocacy as a psychology major, i was excited to take the course entitled, “psychology and medicine,” in my final semester at the university of notre dame. dr. robert white, a neonatologist in the community of south bend, indiana, and an alumnus of the university of notre dame, was one of the faculty members who taught the course. this course was excellent because it connected my interest in psychology with an education and exercises that developed my understanding of my greater purpose in my community as a physician. dr. white introduced me to the concept of advocacy. he taught us that as physicians we will be seen as leaders in our communities, and that we have a duty to use this position to improve and positively impact our communities. i learned from him the importance of getting to know my community and understanding who they were and what their concerns were so that we could work together to make positive changes. dr. robert white’s response on how being involved in advocacy in neonatology promotes a greater sense of purpose and gratitude in his career: in the early days of neonatology, we imagined that we knew how to care for sick newborns. we had learned about surfactant, the basics of nutrition for preterm infants, and how to identify and treat infections and jaundice. we built nicus that were monuments to a particular form of hubris – that babies only needed our wisdom and skills to have their best chance to survive. we didn’t just ignore the importance of parents; we considered them vectors of disease and therefore excluded them for all but a few minutes each day when they could see and perhaps touch their baby but only if they wore masks and gloves. breast milk was “proven” inferior to formula, both in sterility and nutritional value, so that too was excluded. most of the first generation of babies who graduated from modern nicus had minimal human contact during the first weeks or months of life, instead spending their time in an environment that was too bright, too noisy, and too often painful. skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 329 i was determined to learn all i could about the impact of these environmental influences–parental interaction, sound, light, touch, and more–on the health and development of the high-risk babies i was going to spend my career with. new research and new philosophical insights reinforced one another; it soon became apparent both scientifically and philosophically that the optimal place for an ill newborn was in a parent’s arms and, whenever that was not possible, in the most nurturing environment possible for a developing brain. accomplishing this would mean addressing both operational issues – how we saw parents as integral members of a care team rather than visitors and how we understood brain development in the newborn, and structural ones – how we designed our nicus so they would welcome families and promote a sensory experience that was more suitable not only for babies but for families and caregivers. at the end of my training i made the opportunity to build a new world-class nicu one of the conditions of my employment at the hospital near my childhood home. it was a reach; a modest midwestern hospital had no particular reason to commit to the cost or concept of a world-class nicu, but visionary leadership sometimes thrives in unexpected places. five years later, we had built that world-class nicu; one that looked and felt and operated much differently from others around the world. that gave us a platform on which to promote this structural and operational concept of the optimal environment of care for babies, families, and caregivers. over the ensuing years we have written standards, held conferences, written research, review, and opinion papers, and enjoyed seeing more and more research supporting the validity of this concept. the science of neonatology has advanced in many other fields as well; there are many diseases we never see any more, and many more we still see but can treat far more effectively. but the most gratifying aspect of my career is not counting how many babies have been made better by our care but seeing how different the experience is for families, not only in our nicu, but around the world. i cannot take credit for most of this; there are dozens of other visionaries who contributed as much or more to this advocacy, but it has been a wonderful ride on the crest of this wave. that’s how advocacy usually works, after all–it is rarely a solo performance. instead, it takes the work of many, many people–some with vision, some with focus, all with perseverance. shared joy is the best reward–in a large group of advocates, or in the room of a family with their baby, knowing what that would have looked like at the beginning of this journey. developing a passion for the opera i was fortunate to have dr. susan youens as my teacher in a course that studied mozart’s operas during my undergraduate studies at the university of notre dame. the class was exciting for me because i knew of mozart from playing the piano when i was younger, but mostly because of dr. youens’s passion in teaching the class. her great enthusiasm and how she put her heart in the material made me excited to come to the class. as an eager learner, she supported my diligence and invited it. later, i found out from a classmate that she was very successful and well-renowned in the music and opera community. it did not surprise me, as i knew she was very talented. however, i would have never known how successful she was by her sense of humility and her focus and awe on the operas themselves and her students. skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 330 when i was living in new york city, i reconnected with her to inquire about the operas she would recommend seeing at the metropolitan opera. she spoke very highly of la traviata. when i attended the opera, i felt very special to be the student of a teacher who had written the program note for the opera. the experience at the opera made me feel like i had entered into an entirely new world of creativity. dr. youens’s response on how nurturing a passion for the opera and teaching it to others provides a greater sense of purpose and gratitude in her career and how an interest in the opera and fine arts can offer physicians a greater sense of purpose and gratitude in their careers: for many of us, finding our vocation and purpose was mediated through people who made experiences available to us that we might not have had otherwise and that changed us, that made us want to spend our lives exploring beauty. for me, it was being taken to my first opera (richard strauss's der rosenkavalier) by my beloved piano teacher in houston, texas, when i was thirteen years old. i was too young, of course, to understand much of what happened in that ultra-sophisticated and complex creation, but somehow i felt---felt rather than knew---that the final scene was my first immersion in beauty writ large. this was, and is, music that amplifies and exemplifies the big things in life, the things that matter: love and its loss, age, wisdom, acceptance of time and change. later, i was supremely lucky to encounter (life, in one sense, is about those we meet along the way) teachers who awakened me to the music i love most, especially mozart, schubert, and bach, and to my vocation as a teacher and writer who 1) explains what makes the music i love tick and what it means and 2) tries to transfer my adoration of these works and their creators to new acolytes who will love them as much as i do. music for me is the justification for the human race, and i cannot imagine a better way to spend my life than these past decades of teaching students and readers its wonders. it also enables me to "pay it forward" in homage to the magnificent teachers (and a few villains who taught by negative example!) who set me on my path. i have also encountered physicians throughout my life whose sense of the beauty, wonder, tragedy, and passions of the people they tend has been greatly enhanced by their love of music, which teaches us how better to be human. i always tell my students that music goes to the heart of things; since we are all mortal, will all grow sick and die, will pass from the scene, what more magnificent way is there than opera, symphony, song, chamber music and more to teach us how to listen more closely and feel more deeply? childhood most everyone considers their parents to be influential figures in their lives. however, having a dermatologist, dr. mark heibel, as a father has created a unique mentorship experience for me. my parents have been my coaches and best supporters. they always created an environment where i could explore what i was passionate about, and they celebrated my accomplishments and provided unwavering support through my toughest challenges. from an early age, my parents taught me about the importance of service to others. my parents are very generous people. i will always remember how happy it made me to go with my family to the homes of less fortunate families in my hometown to give christmas gifts. i always liked to see the excitement on my mother’s face when she was giving to others. skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 331 my father has heavily influenced my development as a physician, but not in a direct way. i learned from my father great discipline and work ethic. he says he developed it when he had a job working on the paper route when he was young, which was reinforced by being involved in athletics and then being around likeminded individuals in the military during his residency training in dermatology. he probably doesn’t realize how much he’s shaped my approach to life and medicine. i was fortunate to have parents that encouraged me to follow my own dreams. through my own course, i came to be very passionate about dermatology. however, this came later in life, and had it not been for my open exploration in other studies and hobbies prior, i would not have gained such a deep appreciation for the field of dermatology. my parents nurtured my creativity and intellect. they also took part in and supported my ambitious ideas and plans, and they still do now. for example, i have the pleasure of developing ideas for projects and writing academic papers with my father. we also organized a free dermatology clinic in my hometown of lincoln, nebraska, and it has been my most memorable community service project to work together to serve the underserved of our community. dr. mark heibel’s response on how service in the military has provided a greater sense of purpose and gratitude in his life: my family had very modest financial resources when i was growing up, and they could not offer any financial support for my education. after meeting with a student loan officer and recognizing the debt i would incur, i was prepared to decline my acceptance to medical school, until i was accepted into the military health professional scholarship program. this allowed me to attend medical school debtfree in exchange for an obligation of four years of active duty service. with training in dermatology in the military as well, this became eight incredibly impactful years, for which i am very grateful. during this time, i had the opportunity to be educated by and work with a wonderful group of physicians and dermatologists, many of whom have had, and continue to have, a huge impact in the field of dermatology. i also had the opportunity to serve in a combat field artillery brigade in germany during a tumultuous period that included heightened tensions of the cold war, the fall of the berlin wall and reunification of germany, and the beginning of the first gulf war. all of these experiences reinforced my already internalized sense of duty and responsibility to use god-given talents and education in the service of others that had been instilled by my parents and previous education including a medical school that stressed duty and obligations of being in the medical field. this often has led to sacrifices of time and energy – many missed events, children’s athletic activities and programs, vacations, etc., but it is a sacrifice worth making for the greater good. i feel fortunate to live in such a great country and free society, and my past experiences have made me well aware that this is not easily achieved, and we all have responsibilities in order to maintain it. medicine is a profession which comes with great privilege and opportunity. we experience the intricacies of life and work with our society and our community in an intimate way. this is a magnificent responsibility that is associated with great rewards and challenges. developing an conclusion skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 332 awareness of the higher purpose in our lives and professions is valuable not only for creating a life that will be considered to be one of integrity and generosity, but also for instilling resilience through the difficult times. we often develop our sense of purpose through the internalization of values and ideas of people we have met in life. sometimes, these positive influences may not be readily apparent to our conscious mind without deep reflection and thought. each of us has an individualized experience in the world, and the way that we share our talents, enthusiasms, and insights developed along the way is what helps us feel appreciated and helps others feel appreciated. we have discussed our involvement in a variety of experiences and hobbies, including developing an expertise in and serving patient populations in great need, community advocacy, internalizing positive role models within our life experiences to develop a humanistic approach to patient care, creating a curriculum and sharing with medical students the meaning of medical leadership, reading for leisure, exploring music, creating and establishing a form of medical care that provides joy to families and medical professionals, and service to the military. these are only a few out of the infinite possibilities which can nurture a sense of gratitude and purpose in our lives, and we encourage you to expand on these possibilities and share them with others. conflict of interest disclosures: none funding: none corresponding author: haley d. heibel 2110 research row suite 100 dallas, tx 75235 email: hheibel@dermpath.com references: 1. cockerell cj. pressure and disenchantment in physicians—part i: developing an approach to reconnect with what is noble about medicine. clin dermatol. 2016;34(5):650-653. 2. cockerell cj. pressure and disenchantment in physicians—part ii: lessons for physicians from the tao te ching. clin dermatol. 2017;35(1):100-104. 3. shanafelt td, west cp, sinsky c, et al. changes in burnout and satisfaction with work-life integration in physicians and the general us working population between 2011 and 2017. mayo clin proc. 2019;94(9):1681-1694. 4. lewis, d. (2009). galaxy stress research. mindlab international, sussex university, uk. 5. marchalik d, rodriguez a, namath a, et al. the impact of non-medical reading on clinician burnout: a national survey of palliative care providers. ann palliat med. 2019;8(4):428-435. mailto:hheibel@dermpath.com skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 90 in-depth review pulmonary manifestations in pseudoxanthoma elasticum: a review of current literature noa yassky1, nancy wei1, mark lebwohl, md1 1the kimberly and eric j. waldman department of dermatology, icahn school of medicine at mount sinai hospital, new york, new york pseudoxanthoma elasticum (pxe) is an autosomal recessive disease involving the calcification of elastic fibers resulting in ophthalmic, cutaneous, and cardiovascular clinical symptoms and has an estimated prevalence of 1:160,000.1 the disorder is caused by an abcc6 gene mutation that causes loss of function of the mrp6 protein, resulting in dysregulated tissue mineralization.2 characteristic traits of the disease include the presence of angioid streaks on funduscopic examination, cutaneous yellow xanthomatous papules in abstract background: pseudoxanthoma elasticum is a hereditary disease characterized by calcification of elastic fibers that result in cutaneous, ophthalmologic, and cardiovascular complications. as the pulmonary system contains multiple cell types with abundant elastic fibers, pulmonary manifestations are expected, yet not often observed. objective: to review the current literature for clinical, radiologic, and histologic findings of pulmonary manifestations in patients with pseudoxanthoma elasticum. methods: a search of the pubmed computerized database limited to english language case reports and cross-sectional cohort studies as of december 2020 was performed using the key words “pseudoxanthoma elasticum”, “pxe”, “pulm*”, and “lung”. results: a total of 15 patients with clinical, radiologic, or histologic pulmonary manifestations of pxe were identified across four case reports and one cohort study. progressive exertional dyspnea was the only symptom reported. discussion: histologic and/or radiologic investigation of pxe patients who presented with progressive exertional dyspnea revealed calcification and irregularity of the elastic laminae in the pulmonary vasculature, the alveolar septa, or both. additionally, spirometry and diffusion studies in pxe patients revealed a restrictive pattern of lung disease with significantly decreased perfusion compared to controls. conclusions: pxe patients with pulmonary symptoms severe enough to have clinical impact are extremely rare, and thus investigative workup is not recommended. further research is needed to elucidate the clinical impact of lung calcification in pxe patients. introduction skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 91 flexural regions, and various cardiovascular manifestations. serious complications of the disease secondary to elastic calcification of the tunica media layer of both peripheral and central arteries include permanent loss of vision, early onset myocardial infarction, valvular abnormalities such as mitral valve prolapse, intermittent claudication, and gastrointestinal hemorrhage. in the lung, elastin is expressed by pleural mesothelial cells, smooth muscle cells in airways and blood vessels, endothelial cells, and interstitial fibroblasts.3 as the lungs contain extensive networks of elastic laminae, calcification of this system with some clinical manifestations is expected, yet not often reported clinically or in the literature. the purpose of this review is to identify clinical, radiologic, and histologic pulmonary findings of pxe. a pubmed search was conducted with the following terms, “pxe”, “pulm*” and “lung”, and investigation was limited to adult case reports and cohort studies appearing in the english-language literature as of december 2020. articles wherein the full text was not available or of an irrelevant publication type such as literature reviews, conference abstracts, posters, and editorials were excluded. there was a total of four case studies and one cohort study included in this review of pulmonary manifestations in pxe patients. the literature search yielded four case reports and one cohort study from four countries with a total of 15 cases of pulmonary manifestations of pxe. publication years spanned from 1980-2020. a summary of the patient characteristics and clinical manifestations from each report is provided in table 1. figure 1. prisma diagram all four case reports featured pxe patients who complained of progressive dyspnea on exertion and underwent investigative workup that revealed elastic fiber irregularity in two discrete locations: the pulmonary arteries and the alveolar septum. histologic vascular changes included fragmentation of elastic laminae in the tunica medica along with intimal and perivascular fibrosis.4 radiologic lung findings in one patient were limited to calcification and stenosis of the pulmonary artery that led to pulmonary hypertension.5 one patient was found to only have discrete calcified nodules scattered diffusely across the alveolar septum without vascular changes.6 a lung biopsy in a patient with severe dyspnea revealed calcified deposits within thickened alveolar lumina and septa, widespread irregularities in elastic laminae, methods results skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 92 table 1 characteristics of pxe patients with pulmonary manifestations case report year published age (years) patients country diagnostic findings pulmonary symptoms miki et al4 2007 68 1 japan calcification of muscular arterial walls only exertional dyspnea* montani d et al5 2020 39 1 france pulmonary stenosis exertional dyspnea yamamoto n et al6 1996 74 1 japan small, calcified nodules scattered in the alveolar septa only exertional dyspnea jackson a et al7 1980 51 1 malaysia calcification and elastic fiber irregularities in pulmonary arteries, arterioles, venules and alveolar lumina and septa. exertional dyspnea pingel s et al8 2016 52.0 ±9.0 11 germany 11 patients with pathologically low dlco% under 75% 1 patient with tlc <80% no clinical symptoms *attributed to patient’s diagnosis of mitral regurgitation secondary to chordae tendineae rupture, not pulmonary pathology ± denotes standard deviation and intimal fibrosis of arterial, arteriole and venous walls.7 these biopsy findings in addition to xathomatous papules in the axilla led to the diagnosis of pxe during admission. pingel et al measured spirometry results in a cohort of 35 pxe patients and found significantly lower absolute and predicted carbon monoxide diffusing capacity (dlco, dlco%) when compared to controls.8 eleven of these patients (31.5%) had pathologically decreased dlco values. absolute total lung capacity (tlc) was significantly decreased in the pxe group; however, only one patient presented with a predicted tlc <80%. none of the patients were found to have abnormalities in predicted vital capacity (vc%) or forced expiration in 1 second (fev1%). this literature review demonstrates that elastic fiber calcification of the pulmonary arteries and alveolar septa can be a rare manifestation of pxe. all four patients who complained of progressive exertional dyspnea had radiologic and/or histologic evidence of pulmonary calcification. theoretically, the significantly decreased tlc and dlco values in pxe patients is consistent with decreased perfusion and a restrictive pattern of lung disease. one possible explanation for this is how pxe induced calcification in pulmonary arteries can result in stenosis and thus perfusion defects without effect on ventilation. calcification and decreased elasticity of in alveolar septum can manifest as subclinical interstitial lung disease with decreased tlc. continual calcification of these two regions over time could explain the insidious onset of progressive exertional dyspnea reported. however, spirometry abnormalities in pxe patients did not correlate with the presence of pulmonary symptoms. long term observation for the development of dyspnea in the pxe cohort could be helpful in determining whether spirometry could be used as a screening tool for asymptomatic patients. in addition, while calcification of small arteries in the ocular, gastrointestinal, discussion skin march 2021 volume 5 issue 2 copyright 2021 the national society for cutaneous medicine 93 and rarely cerebrovascular systems can result in bleeding complications of these areas, there were no reported cases of pulmonary hemorrhage. 9 currently, there is no standard of care for pxe or its pulmonary manifestations. due to the exceedingly rare nature of clinically significant symptoms, screening and referral to pulmonary specialists for monitoring is not recommended. even in the presence of progressive exertional dyspnea, the impact of diagnostic imaging on overall management in pxe patients is minimal. although uncommon, physicians might consider pxe as a diagnosis of exclusion for unexplained progressive exertional dyspnea if found in conjunction with classic cutaneous lesions or ocular findings. further research must be conducted to evaluate the long-term clinical impact of pulmonary manifestations on pxe patients and possible response to experimental systemic therapies currently in development. conflict of interest disclosures: mark lebwohl is an employee of mount sinai and receives research funds from: abbvie, amgen, arcutis, boehringer ingelheim, dermavant, eli lilly, incyte, janssen research & development, llc, leo pharmaceuticals, ortho dermatologics, pfizer, and ucb, inc.and is a consultant for aditum bio, allergan, almirall, arcutis inc., avotres therapeutics, birchbiomed inc., bmd skincare, boehringer ingelheim, bristol-myers squibb, cara therapeutics, castle biosciences, corrona, dermavant sciences, evelo, facilitate international dermatologic education, foundation for research and education in dermatology, inozyme pharma, kyowa kirin, leo pharma, meiji seika pharma, menlo, mitsubishi, neuroderm, pfizer, promius/dr. reddy’s laboratories, serono, theravance, and verrica. funding: none corresponding author: nancy wei icahn school of medicine at mount sinai hospital the kimberly and eric j. waldman department of dermatology 5 east 98th street, 5th floor new york, ny 10029 phone: 212-241-6758 email: nancy.wei@mountsinai.org references: 1. bergen, arthur a. b., et al. “abcc6 and pseudoxanthoma elasticum.” pflügers archiv european journal of physiology, vol. 453, no. 5, 2006, pp. 685–691., doi:10.1007/s00424-005-0039-0. 2. ringpfeil f, mcguigan k, fuchsel l, et al. pseudoxanthoma elasticum is a recessive disease characterized by compound heterozygosity. j invest dermatol. 2006;126(4):782-786. doi:10.1038/sj.jid.5700115 3. mecham rp. elastin in lung development and disease pathogenesis. matrix biol. 2018 nov;73:6-20. doi: 10.1016/j.matbio.2018.01.005. epub 2018 jan 11. pmid: 29331337; pmcid: pmc6041195. 4. miki k, yuri t, takeda n, takehana k, iwasaka t, tsubura a. an autopsy case of pseudoxanthoma elasticum: histochemical characteristics. med mol morphol. 2007 sep;40(3):172-7. doi: 10.1007/s00795007-0368-5. epub 2007 sep 18. pmid: 17874051. 5. montani d, jaïs x, humbert m, sitbon o. pulmonary hypertension complicating pulmonary artery involvement in pseudoxanthoma elasticum. am j respir crit care med. 2020 sep 1;202(5):e90-e91. doi: 10.1164/rccm.202002-0248im. pmid: 32413269. 6. yamamoto n, hasegawa h, sakamoto h, numata h, fukuda t, komatsu s, kido y. [pseudoxanthoma elasticum with pulmonary calcification]. nihon kyobu shikkan gakkai zasshi. 1996 jun;34(6):716-20. japanese translated to english. pmid: 8741541. 7. jackson a, loh cl. pulmonary calcification and elastic tissue damage in pseudoxanthoma elasticum. histopathology. 1980 nov;4(6):607-11. doi: 10.1111/j.1365-2559.1980.tb02956.x. pmid: 7439889. 8. pingel s, passon sg, pausewang ks, blatzheim ak, pizarro c, tuleta i, gliem m, charbel issa p, schahab n, nickenig g, skowasch d, schaefer ca. pseudoxanthoma elasticum also a lung disease? the respiratory affection of patients with pseudoxanthoma elasticum. plos one. 2016 sep 13;11(9):e0162337. doi: 10.1371/journal.pone.0162337. pmid: 27622520; pmcid: pmc5021259. 9. liaqat m, heymann wr. anticoagulation in patients with pseudoxanthoma elasticum. skinmed. 2017;15(4):319-320. published 2017 aug 1. conclusion synopsis objective to determine whether increased disease control in psoriasis with treatment translates into improvements in quality of life. methods patients reaching different absolute pasi thresholds were assessed for simultaneous achievement of dlqi 0/1. results week 52 conclusion patients treated with bimekizumab more frequently achieved pasi≤2 by week 52, with the majority of these patients also achieving dlqi 0/1. objective to examine how improved disease control translates to greater quality of life in patients with moderate to severe plaque psoriasis receiving bimekizumab compared with ustekinumab and placebo. background • psoriasis negatively impacts patients’ quality of life,1 and therefore it is important to determine whether improvements in disease control achieved with treatment may also be reflected in greater quality of life. • bimekizumab is a monoclonal igg1 antibody that selectively inhibits interleukin (il)-17f in addition to il-17a, both of which have a pivotal role in psoriasis immunopathogenesis.2-5 • absolute psoriasis area and severity index (pasi) and dermatology life quality index (dlqi) were assessed in patients with moderate to severe plaque psoriasis being treated with bimekizumab versus (vs) ustekinumab and placebo. methods • in be vivid (nct03370133) patients were randomized to bimekizumab through week 52, ustekinumab through week 52 or placebo; patients randomized to placebo switched to bimekizumab at week 16 (figure 1). • psoriasis severity was assessed by pasi, where pasi=0 indicated complete skin clearance and pasi≤2, a relevant disease endpoint for a treat to target approach in psoriasis,6 indicated disease control. • patients completed the dlqi questionnaire throughout treatment; dlqi of 0 or 1 indicated no impact on quality of life.7 • to evaluate how clinical response translates into health-related quality of life in these post hoc analyses, patients achieving dlqi 0/1 were grouped by pasi=0, pasi≤2, 2<pasi<5, and pasi≥5 responses at the same timepoint. • weeks 4 and 16 data for all patients, and week 52 data for bimekizumaband ustekinumab-randomized patients, are presented here. results patient population • in be vivid, 321 patients were randomized to bimekizumab, 163 to ustekinumab, and 83 to placebo (table 1). pasi and dlqi outcomes • at week 4, after one dose, a greater proportion of bimekizumab-treated patients rapidly achieved superior rates of pasi=0 and pasi≤2 as compared to ustekinumab (nominal p<0.0001 for both) and placebo (nominal p=0.0019 and nominal p<0.0001, respectively); this was further improved and sustained through week 16 to week 52 (table 2). • similarly, rapid improvements in quality of life were seen with bimekizumab; dlqi 0/1 achievement by week 4 was greater with bimekizumab as compared to ustekinumab and placebo (nominal p<0.0001 for both). quality of life continued to improve through to week 52, and remained greater in bimekizumab patients vs ustekinumab (nominal p=0.0007) (table 2). • across all treatment arms, higher disease control translated into greater improvements in quality of life. this was more pronounced in bimekizumab than ustekinumab with 44.6% vs 17.3% achieving both pasi=0 and dlqi 0/1 at week 16, increasing to 68.6% vs 40.3% at week 52 (figure 2). similar trends were seen when considering pasi≤2; 65.1% of patients treated with bimekizumab vs 34.6% with ustekinumab achieved both pasi≤2 and dlqi 0/1 at week 16, increasing to 83.8% vs 59.7% at week 52 (figure 3). conclusions greater levels of disease control seen with bimekizumab treatment, as compared to ustekinumab, translated to greater quality of life as measured by dlqi. after one year of treatment with bimekizumab, almost 70% of patients achieved complete skin clearance and reported that psoriasis had no impact on their quality of life, compared to 40% with ustekinumab. k. gordon,1 p. foley,2 p. rich,3 k. duffin,4 a. pinter,5 c.e.m. griffiths,6 m. wang,7 v. vanvoorden,8 f. staelens,9 v. ciaravino,10 j.f. merola11 bsa: body surface area; dlqi: dermatology life quality index; iga: investigator’s global assessment; oc: observed case; pasi: psoriasis area and severity index; q4w: every 4 weeks; q12w: every 12 weeks; sd: standard deviation; vs: versus. figure 1 study design institutions: 1medical college of wisconsin, milwaukee, wisconsin, usa; 2the university of melbourne, st. vincent’s hospital melbourne, fitzroy and probity medical research inc., skin health institute, carlton, victoria, australia; 3oregon dermatology and research center, portland, oregon, usa; 4department of dermatology, university of utah, salt lake city, utah, usa; 5university hospital frankfurt, frankfurt am main, germany; 6dermatology centre, the university of manchester, manchester, uk; 7ucb pharma, raleigh, north carolina, usa; 8ucb pharma, brussels, belgium; 9ucb pharma, braine-l’alleud, belgium; 10ucb pharma, colombes, france; 11harvard medical school, brigham and women’s hospital, boston, massachusetts, usa bimekizumab versus ustekinumab in plaque psoriasis: lasting efficacy translates to rapid and sustained improvements in quality of life in the be vivid multicenter, randomized, double-blinded phase 3 trial presented at winter clinical 2021 virtual congress | january 16–24 references: 1bhosle mj. health qual life outcomes 2006;4:35; 2glatt s. br j clin pharmacol 2017;83:991–1001; 3papp ka. j am acad dermatol 2018;79:277–86.e10; 4durham l. curr rheumatol rep 2015;17:55; 5fujishima s. arch dermatol res 2010;302:499–505; 6mahil sk. br j dermatol 2020;182:1158–66; 7hongbo y. j invest dermatol 2005;125:659–64. author contributions: substantial contributions to study conception/design, or acquisition/analysis/interpretation of data: kg, pf, pr, kd, ap, cemg, mw, vv, fs, vc, jfm; drafting of the publication, or revising it critically for important intellectual content: kg, pf, pr, kd, ap, cemg, mw, vv, fs, vc, jfm; final approval of the publication: kg, pf, pr, kd, ap, cemg, mw, vv, fs, vc, jfm. author disclosures: kg: honoraria and/or research support from abbvie, almirall, amgen, boehringer ingelheim, bristol myers squibb, celgene, dermira, eli lilly, janssen, novartis, pfizer, sun pharma, and ucb pharma; pf: grant support from abbvie, amgen, celgene, eli lilly, janssen, merck, novartis, pfizer, sanofi, and sun pharma; investigator for abbvie, amgen, astrazeneca, bristol myers squibb, boehringer ingelheim, botanix, celgene, celtaxsys, csl, cutanea, dermira, eli lilly, galderma, genentech, geneseq, gsk, hexima, janssen, leo pharma, merck, novartis, pfizer, regeneron, reistone, roche, sanofi genzyme, sun pharma, ucb pharma, and valeant/bausch health; served on the advisory board for abbvie, amgen, bristol myers squibb, celgene, eli lilly, galderma, janssen, leo pharma, mayne pharma, merck, novartis, pfizer, sanofi genzyme, sun pharma, ucb pharma, and valeant/bausch health; consultant for bristol myers squibb, eli lilly, janssen, novartis, pfizer, ucb pharma, and wintermute; received travel grants from abbvie, eli lilly, janssen, leo pharma, merck, novartis, pfizer, roche, and sanofi; speaker for or received honoraria from abbvie, celgene, eli lilly, galderma, janssen, leo pharma, merck, novartis, pfizer, and roche; pr: research grants due to being principal investigator from abbvie, arcutis, bristol myers squibb, centocor, dermavant, eli lilly, kadmon, merck, novartis, pfizer, sun pharma, and ucb pharma; kd: received grants/investigator for abbvie, amgen, bristol myers squibb, celgene, eli lilly, janssen, novartis, pfizer, regeneron, sienna, stiefel, and ucb pharma; speaker’s bureau for novartis (non-promotional only); consultant/advisory board for abbvie, amgen, bristol myers squibb, celgene, eli lilly, janssen, novartis, ortho dermatologic, pfizer, sienna, stiefel, and ucb pharma; ap: investigator and/or speaker and/or advisor for abbvie, almirall, amgen, biogen, boehringer ingelheim, celgene, eli lilly, galderma, gsk, hexal, janssen, leo pharma, mc2, medac, merck serono, mitsubishi pharma, msd, novartis, pfizer, regeneron, roche, sandoz, schering-plough, tigercat pharma, and ucb pharma; cemg: honoraria and/or grants from abbvie, almirall, bms, celgene, eli lilly, galderma, leo pharma, janssen, novartis, pfizer, sandoz, and ucb pharma; mw, vv, fs, vc: employees of ucb pharma; jfm: consultant and/or investigator for abbvie, arena, avotres, biogen, bristol myers squibb, dermavant, eli lilly, emd-serono, janssen, leo pharma, merck, novartis, regeneron, sanofi, sun pharma, pfizer, and ucb pharma. acknowledgements: this study was funded by ucb pharma. we would like to thank the patients and their caregivers in addition to all the investigators and their teams who contributed to this study. the authors acknowledge mylene serna, pharmd, ucb pharma, smyrna, ga, usa and susanne wiegratz, msc, ucb pharma, monheim am rhein, germany for publication coordination; eva cullen, phd, ucb pharma, brussels, belgium for critical review; kristian clausen, mph, costello medical, cambridge, uk for medical writing and editorial assistance; and the costello medical design team for design support. all costs associated with development of this poster were funded by ucb pharma. previously presented at eadv 2020 virtual congress | october 29–31 abimekizumab dosing was 320 mg regardless of weight, while ustekinumab dosing was based on weight: patients ≤100 kg at baseline received one ustekinumab 45 mg injection and one placebo injection, patients >100 kg at baseline received two ustekinumab 45 mg injections; bbe bright: nct03598790. table 1 baseline characteristics abimekizumab dosing was 320 mg regardless of weight, while ustekinumab dosing was based on weight: patients ≤100 kg at baseline received one ustekinumab 45 mg injection and one placebo injection, patients >100 kg at baseline received two ustekinumab 45 mg injections; bin each treatment group, one patient with mild iga score was mistakenly enrolled. figure 2 simultaneous achievement of pasi=0 and dlqi 0/1 at weeks 16 and 52 (oc)a n numbers represent the number of patients with both a pasi and dlqi assessment at that time point. apatients randomized to placebo not shown. aweek 52 data not shown for patients randomized to placebo as they switched to bimekizumab treatment at week 16. denominators used represent the number of patients in that treatment group with an assessment at that time point for each type of measure (pasi or dlqi). of all patients, 283 randomized to bimekizumab, 141 to ustekinumab and 69 to placebo completed the study to week 52. table 2 number (%) of patients achieving absolute pasi scores and dlqi 0/1 (oc) bimekizumab 320 mg q4w (n=321)a ustekinumab 45/90 mg q12w (n=163)a placebo (n=83) age (years), mean ± sd 45.2 ± 14.0 46.0 ± 13.6 49.7 ± 13.6 male, n (%) 229 (71.3) 117 (71.8) 60 (72.3) caucasian, n (%) 237 (73.8) 120 (73.6) 63 (75.9) weight (kg), mean ± sd 88.7 ± 23.1 87.2 ± 21.1 89.1 ± 26.4 duration of psoriasis (years), mean ± sd 16.0 ± 11.6 17.8 ± 11.6 19.7 ± 13.8 pasi, mean ± sd 22.0 ± 8.6 21.3 ± 8.3 20.1 (6.8) bsa (%), mean ± sd 29.0 ± 17.1 27.3 ± 16.7 27.0 ± 16.3 iga, n (%)b 3: moderate 201 (62.6) 96 (58.9) 54 (65.1) 4: severe 119 (37.1) 66 (40.5) 28 (33.7) dlqi total, mean ± sd 9.9 ± 6.3 11.0 ± 6.9 10.0 ± 6.8 any prior systemic therapy, n (%) 267 (83.2) 132 (81.0) 64 (77.1) prior biologic therapy, n (%) 125 (38.9) 63 (38.7) 33 (39.8) absolute pasi dlqi 0/1 pasi=0 pasi≤2 w e e k 4 bimekizumab 48/318 (15.1) 148/318 (46.5) 120/320 (37.5) ustekinumab 2/161 (1.2) 10/161 (6.2) 18/161 (11.2) placebo 2/81 (2.5) 2/81 (2.5) 5/80 (6.3) w e e k 1 6 bimekizumab 188/307 (61.2) 273/307 (88.9) 216/308 (70.1) ustekinumab 35/156 (22.4) 84/156 (53.8) 69/156 (44.2) placebo 0/76 (0.0) 3/76 (3.9) 10/76 (13.2) w e e k 5 2 a bimekizumab 207/277 (74.7) 263/277 (94.9) 240/277 (86.6) ustekinumab 63/139 (45.3) 98/139 (70.5) 103/141 (73.0) 80% 60% 40% 20% 100% 0% bimekizumab ustekinumab pasi≤2 only pasi≤2 + dlqi 0/1 70.5% 94.9% 59.7% 83.8% n=321 n=163 n=83 week 16baseline week 52 2–5 weeks bimekizumab 320 mg q4wa bimekizumab 320 mg q4waplacebo ustekinumab 45/90 mg q12wa 20 weeks after last dose: safety follow-up open-label extension study (be bright)b screening initial treatment period active comparator period maintenance period 4:1:2 randomization n=567 ustekinumab bimekizumab bimekizumab week 16 week 52 ustekinumab pasi=0: pasi=0 and dlqi 0/1: bimekizumab ustekinumab 61.2% 74.7% 45.3% n=307 n=277 n=156 n=139 44.6% 68.6% 17.3% 40.3% 22.4% figure 3 simultaneous achievement of pasi≤2 and dlqi 0/1 at weeks 16 and 52 (oc)a n numbers represent the number of patients with both a pasi and dlqi assessment at that time point. apatients randomized to placebo not shown. ustekinumab bimekizumab pasi≤2: pasi≤2 and dlqi 0/1: bimekizumab ustekinumab bimekizumab week 16 week 52 ustekinumab n=307 n=277 n=156 n=139 88.9% 83.8% 94.9% 34.6% 59.7% 70.5% 53.8% 65.1% unthsc rad theme references combination therapy with short contact topical calcipotriene foam and fluorouracil following cryotherapy for actinic keratosis • actinic keratoses (aks) are lesions characterized by a proliferation of dysplastic keratinocytes that occur on photoaged skin as a result of ultraviolet radiation. they have malignant potential and are recognized precursors to squamous cell carcinoma (scc).1,2 • the estimated annual risk of evolution of ak to scc is between 0.15% and 80% for patients with multiple aks. because it is not feasible to predict which ak lesions will become malignant, treatment of all aks is recommended.1 • current treatment for ak lesions includes cryotherapy (ln2) and topical 5-fluorouracil (5-fu). patients have reported local adverse reactions with this therapy including erythema, dryness, pruritus, and irritation.2 • vitamin d derivatives have demonstrated anti-proliferative properties in cancer treatment via stimulation of the vitamin d3 receptor, which can be found on keratinocytes.3 • topical vitamin d has been shown to decrease the number of ak lesions. recent research suggests that topical vitamin d derivatives may be efficacious in the treatment of aks.3 • a total of fifteen patients (30%) treated with 5-fu cream and five patients (10%) treated with 5-fu cream and topical calcipotriene foam experienced some grade of irritation during their treatment course (figure 5). irritation was defined as patient-reported irritation due to the topical treatment. • reported symptoms of irritation included non-persistent mild erythema, dryness, and/or pruritus. no pain, scabbing, or erosion was reported. • cases of irritation resolved within two weeks of topical treatment discontinuation. • no patients discontinued treatment due to irritation. • the combination of cryotherapy and short-contact treatment with 5-fu cream and topical calcipotriene foam (group # 3) resulted in a statistically significant greater decrease in total ak lesions than ln2 alone (group #1) or ln2 followed by short-contact with topical 5-fu (group #2) at month 6 (p=0.00952). • a reduction in mean total ak counts was observed at each body site in group #3 in comparison to group #1 or group #2. • reductions in total mean ak lesion counts were demonstrated at months 1 and 3, with statistically significant decrease in total ak lesion count at month 6 (p=0.03383). • greater percent reduction in mean total ak lesion counts was also observed in patients treated with ln2 followed by shortcontact combination therapy of calcipotriene foam with 5-fu than patients being treated with ln2 alone and ln2 followed by shortcontact 5-fu. • treatment with ln2 followed by the short-contact treatment with calcipotriene foam in addition to 5-fu was associated with a lower rate of irritation (10%) than treatment with ln2 followed by short-contact treatment with topical 5-fu alone (30%). • irritation rates were also markedly lower than those reported in clinical trials (39%).4 it is likely that the short-contact method of application resulted in tolerability improvement. • cryotherapy followed by short contact topical calcipotriene foam in combination with 5-fluorouracil cream may offer increased efficacy and safety in the treatment of actinic keratoses. • multicenter, randomized, placebo-controlled trials are needed to confirm these findings. • a decrease in total ak lesion count was noted at months1, 3, and 6 using measures of central tendency, but a statistically significant decrease in total lesion count was only observed at month 6 compared to baseline count (p=0.03383). • upon further analysis, treatment with ln2 followed by shortcontact topical 5-fu and calcipotriene foam (group #3) showed a greater mean decrease in number of aks than treatment with ln2 alone (group #1) or ln2 followed by short-contact topical 5-fu (group #2) (figure 1). • using tukey contrasts, a statistical difference in total ak lesions counts was only observed in group #3 (ln2 followed by short-contact 5-fu and calcipotriene foam) (p=0.0255) (figure 2). -25% -15% -5% 5% 15% 25% 35% month 1 month 3 month 6 figure 3. percent reduction in mean* total lesions by treatment at 1-, 3-, and 6-month follow-up visits ln2 ln2 + 5-fu ln2 + 5-fu + calcipotriene foam introduction results conclusions 1. dodds, a., a. chia, and s. shumack, actinic keratosis: rationale and management. dermatol ther (heidelb), 2014. 4(1): p. 11-31. 2. seckin, d., et al., can topical calcipotriol be a treatment alternative in actinic keratoses? a preliminary report. j drugs dermatol, 2009. 8(5): p. 451-4. 3. seckin, d., et al., can topical calcipotriol be a treatment alternative in actinic keratoses? a preliminary report. j drugs dermatol, 2009. 8(5): p. 451-4. 4. cunningham, t.j., et al., randomized trial of calcipotriol combined with 5-fluorouracil for skin cancer precursor immunotherapy. j clin invest, 2017. 127(1): p. 106-116. methods • this was a retrospective analysis of patients presenting with aks in a clinical dermatology office setting. • three treatment groups were evaluated with 50 patients per group: 1) ln2, 2) ln2 with short-contact topical 5-fu 1% cream, 3) ln2 with short-contact topical 5-fu 1% cream and calcipotriene foam • lesion count was assessed and cryotherapy was administered on ak lesions at baseline visit. patients in the groups #2 and #3 were then instructed to begin short-contact topical therapy cycles: nightly for 5 days on the face and 7 days on other affected areas, off for 2-week interval, and then repeat, with 5-fu (group #2) or both 5-fu and calcipotriene foam (group #3) follow-up visits were scheduled for 1, 3, and 6 months. • at each follow-up visit, ak lesion count was assessed and ak’s treated with cryotherapy. patients were also asked to report any side effects. • patient assessments and lesion counts were only performed at scheduled follow-up evaluation visits. • ancova analysis was used to adjust for imbalances in baseline ak lesion count. angela yen moore, md 1 2, 3; madalyn nguyen, oms-ii4 1arlington research center, arlington, tx; 2baylor university medical center, dallas, tx; 3university of texas medical branch at galveston, tx; 4texas college of osteopathic medicine, unthsc, fort worth, tx 0 5 10 15 20 25 face chest back arms figure 4. mean lesion count per body site at each visit for ln2 + 5-fu + calcipotriene foam baseline (n=50) month 1 (n=24) month 3 (n=22) month 6 (n=19) 0% 5% 10% 15% 20% 25% 30% 35% ln2 + 5-fu (n=50) ln2 + 5-fu + calcipotriene foam (n=50) figure 5. treatment-associated irritation figure 1. ancova summary table 6 months treatment p-value mean change in lesion count confidence interval (95%) ln2 4.21e-07 17.212 11.055 – 23.369 ln2 + 5-fu 0.16420 -4.741 -11.467 – 1.985 ln2 + 5-fu + calcipotriene foam 0.00952 -8.818 -15.415 – -2.221 • a greater percent reduction in total ak lesion count was observed in patients treated with ln2 followed by short-contact combination therapy of calcipotriene foam with 5-fu than patients being treated with ln2 alone and ln2 followed by shortcontact 5-fu (figure 3). • compared with baseline, the mean lesion count decreased over the course of treatment at each body site evaluated (figure 4). • two patients in group #1 (treated with ln2 alone), one patient in group #2 (treated with ln2 and short-contact topical 5-fu), and two patients in group #3 (treated with ln2 and short-contact topical calcipotriene foam with 5-fu) were determined to be noncompliant due to failure to maintain regularly scheduled follow-up visits at 1, 3, or 6 months. *means after controlling for variations in baseline lesion count. figure 2. tukey contrasts 6 months treatment p-value ln2 + 5-fu – ln2 0.3434 ln2 + 5-fu + calcipotriene foam – ln2 0.0255 **research partially funded by unrestricted educational grant from mayne pharma skin january 2018 volume 2 issue 1 copyright 2018 the national society for cutaneous medicine 59 brief articles capecitabine-induced subacute cutaneous lupus erythematosus in a patient with systemic lupus erythematosus alyx rosen md a , evan darwin bs a , jennifer n. choi md b a university of miami miller school of medicine, department of dermatology and cutaneous surgery, miami, fl b northwestern university feinberg school of medicine department of dermatology, chicago, il drug-induced subacute cutaneous lupus erythematosus (di-scle) is characterized by histopathological and immunopathological features of typical scle that are induced by a drug, dissipate with the drug’s removal, and recur with reexposure to the agent. 1 capecitabine is a fluoropyrimidine chemotherapy prodrug of 5fluorouracil (5-fu) used for the treatment of metastatic breast and colorectal cancers. 2 dermatologic conditions commonly associated with capecitabine include palmar-plantar erythrodysesthesia, photoeruption, dermatitis, leopard-like vitiligo, erythematous rash, and onycholysis. 3 here we present a case of di-scle in association with capecitabine in the setting of known systemic lupus erythematosus (sle). a 68-year-old female with colon adenocarcinoma presented to the dermatology clinic with a photosensitive rash without pain or pruritus on her upper body that began eight weeks after initiating capecitabine therapy. her past medical history was significant for sle diagnosed 16 years prior, which was well-controlled with hydroxychloroquine. the patient denied a history of skin lesions with her lupus. on examination, the patient had several 0.5-2 abstract capecitabine is a fluoropyrimidine chemotherapy prodrug of 5-fluorouracil (5-fu) used in the treatment of metastatic breast and colorectal cancers. drug-induced subacute cutaneous lupus erythematosus (di-scle) is a rare side effect of capecitabine therapy, with eight cases previously reported. we report a case of di-scle in a patient with a documented history of systemic lupus erythematosus (sle). this is the second documented case of di-scle in a patient with a past medical history of sle, and provides evidence that there may be an increased risk of di-scle in these patients. further research should examine whether patients with sle are at greater risk for this adverse event. introduction case report skin january 2018 volume 2 issue 1 copyright 2018 the national society for cutaneous medicine 60 cm thin pink annular scaly papules and plaques on her forearms, posterior neck, and anterior chest in a photodistribution [fig. 1]. patchy scarring alopecia was noted on the scalp, along with several 0.5-1 cm pink scaly papules and plaques on her upper cutaneous lip and bilateral cheeks. the oral mucosa was clear. review of systems revealed no associated systemic symptoms, such as fevers, fatigue, arthralgias, chest pain, or neurologic symptoms. a biopsy was obtained from the patient’s left forearm. histopathology showed an interface lymphocytic infiltrate with basal vacuolar changes and necrotic keratinocytes, telangiectasias with a perivascular lymphocytic infiltrate, and dermal edema. the patient’s laboratory values showed a positive ana titer of 1:640 and an anti-dsdna antibody level of 498, up from 396 immediately prior to starting capecitabine. c3 complement levels fell from 79 to 66, and c4 dropped from 14 to 10. she was weakly positive for antissa/ro, anti-smith, and anti-histone antibodies; however, baseline levels of these antibodies were not performed prior to capecitabine therapy. all other laboratory data were unremarkable. the patient was prescribed triamcinolone 0.1% cream twice daily and strict sun protection. due to her symptoms and histologic and laboratory results, she was diagnosed with di-scle and capecitabine was discontinued. at two-week follow-up, the rash had significantly improved, with decreased erythema and scaling of the lesions. two months after drug discontinuation, the rash had completely resolved [fig. 2]. four months after drug discontinuation, the patient’s ana titer fell to 1:320. figure 1. annular scaly pink papules and plaques on the bilateral forearms. figure 2. resolution of rash two months after drug discontinuation. skin january 2018 volume 2 issue 1 copyright 2018 the national society for cutaneous medicine 61 di-scle from capecitabine therapy is rare. in addition to our patient, eight other cases of capecitabine-induced scle have been reported [table 1]. while the antibody profile varied slightly between cases, every patient had an elevated ana and positive anti-ssa/ro antibodies, and most demonstrated negative anti-histone and antidsdna autoantibodies. 1-8 one other patient also had a history of sle, making this the second case of di-scle from capecitabine in the setting of underlying sle and highlighting a potential association. 6 additionally, no other cases of di-scle from other chemotherapies in patients with underlying sle have been described; however, cases of idiopathic scle exacerbated by either docetaxel or doxorubicin have been reported. 9-10 the patients in these cases had well-controlled disease and positive serology for antissa/ro antibodies prior to the onset of chemotherapy, and their skin rash resolved with cessation of the causative drug. 9-10 table 1. cases of subacute cutaneous lupus erythematosus from capecitabine author and year age/sex ana antidsdna antiro/ssa antihistone medical history of sle or other rheumatic disease weger et al. 2008 3 77/female + + no fernandes et al. 2009 7 49/female + 1:640 + + no floristan et al. 2009 8 66/female before therapy 1:160 after therapy: 1:1280 not reported + seronegative polyarthritis with occasional positive ana kindem et al. 2013 2 78/female + 1:640 + no ko et al. 2013 1 72/female + >1:2560 + no fongue et al. 2014 6 50/female not reported not reported + not reported sle kim et al. 2016 5 67/female + >1:320 + no li et al. 2016 4 74/female + 1:1000 + no our case 2017 68/female + 1:640 + + + sle discussion skin january 2018 volume 2 issue 1 copyright 2018 the national society for cutaneous medicine 62 one possible explanation for di-scle in association with sle is the presence of preexisting anti-ssa/ro antibodies in sle patients, which may be a risk factor for the development of scle in the correct setting, such as exposure to a chemotherapeutic agent. a large multicenter cohort study demonstrated that 32% of childhood-onset sle patients had positive anti-ssa/ro antibodies. 11 additionally, 5-fu may translocate ssa/ro antigens to the surface of keratinocytes, leading to lupus-like eruptions and possibly higher rates of scle in patients with underlying sle and elevated autoantibodies. 11,12 alternatively, one case showed a patient who developed di-scle from capecitabine that did not recur with subsequent administration of 5-fu. 5 this suggests a novel pathophysiology for the induction of scle from capecitabine that is distinct from 5-fu, although the mechanism is still unclear. while the pathophysiology of di-scle requires further investigation, it is also important to differentiate di-scle from other diagnoses such as di-sle or a flare of underlying sle. di-scle is distinguished from di-sle by its clinical characteristics and immunologic profile. di-scle will typically present as a skin rash and patients have positive anti-ssa/ro antibodies. 2 the cutaneous lesions of di-scle classically present as generalized annular polycyclic or papulosquamous plaques. 3 conversely, disle patients present more often with systemic symptoms, such as arthralgias and serositis, than with a skin rash and can have anti-histone antibodies. 2 di-scle is distinguishable from a flare of underlying sle based on the disease time course. if the rash begins with onset of the drug, subsides with the drug’s cessation, and recurs with re-exposure, it is likely discle. additionally, if the new rash is substantively different from the patient’s typical sle presentation, then the presence of the rash in the setting of a new drug exposure most likely represents a drug adverse event. our patient presented with a new-onset rash that was clinically, immunologically, and histopathologically consistent with scle several weeks after starting capecitabine therapy while on oral hydroxychloroquine therapy for her sle. her rash improved with topical steroids and ultimately resolved with cessation of capecitabine. no systemic symptoms suggestive of an sle flare occurred simultaneously. in conclusion, this case highlights an occurrence of di-scle secondary to capecitabine therapy in a patient with sle. this is the second case of a patient on capecitabine that developed di-scle with a documented history of sle and raises concern that sle in the setting of capecitabine or possibly other chemotherapeutic agents may predispose patients to this reaction. patients receiving capecitabine should be monitored for the development of scle during treatment, with clinicians having a low threshold to perform a skin biopsy and laboratory work-up for possible scle if a patient develops new pink scaly papules in a photodistributed pattern. more research should be undertaken to determine the pathophysiology of di-scle in patients with underlying sle. skin january 2018 volume 2 issue 1 copyright 2018 the national society for cutaneous medicine 63 conflict of interest disclosures: none. funding: none. corresponding author: jennifer n. choi, md 676 n. st. clair street, arkes family pavilion suite 1600 chicago, illinois 60611-2997 312-921-6097 jennifer.choi@northwestern.edu references: 1. ko jh, hsieh ci, chou cy, wang kh. capecitabine-induced subacute cutaneous lupus erythematosus: report of a case with positive rechallenge test. the journal of dermatology. 2013;40(11):939-940. 2. kindem s, llombart b, requena c, et al. subacute cutaneous lupus erythematosus after treatment with capecitabine. the journal of dermatology. 2013;40(1):75-76. 3. weger w, kranke b, gerger a, salmhofer w, aberer e. occurrence of subacute cutaneous lupus erythematosus after treatment with fluorouracil and capecitabine. j am acad dermatol. 2008;59(2 suppl 1):s4-6. 4. li z, jiang n, xu y. the concurrence of subacute cutaneous lupus erythematosus and hand-foot syndrome in a patient undergoing capecitabine chemotherapy. the australasian journal of dermatology. 2016;57(1):e14-16. 5. kim wi, kim jm, kim gw, et al. subacute cutaneous lupus erythematosus induced by capecitabine: 5-fu was innocent. journal of the european academy of dermatology and venereology : jeadv. 2016;30(11):e163e164. 6. fongue j, meunier b, lardet d, et al. capecitabine-induced subacute cutaneous lupus: a case report. annales de dermatologie et de venereologie. 2014;141(10):593-597. 7. fernandes nf, rosenbach m, elenitsas r, kist jm. subacute cutaneous lupus erythematosus associated with capecitabine monotherapy. archives of dermatology. 2009;145(3):340-341. 8. floristan u, feltes ra, sendagorta e, et al. subacute cutaneous lupus erythematosus induced by capecitabine. clinical and experimental dermatology. 2009;34(7):e328329. 9. marchetti ma, noland mm, dillon pm, greer ke. taxane associated subacute cutaneous lupus erythematosus. dermatology online journal. 2013;19(8):19259. 10. lebeau s, tambe s, sallam ma, et al. docetaxel-induced relapse of subacute cutaneous lupus erythematosus and chilblain lupus. journal der deutschen dermatologischen gesellschaft : jddg. 2013;11(9):871-874. 11. novak gv, marques m, balbi v, et al. antiro/ssa and anti-la/ssb antibodies: association with mild lupus manifestations in 645 childhood-onset systemic lupus erythematosus. autoimmunity reviews. 2017;16(2):132-135. 12. adachi a, nagai h, horikawa t. antissa/ro antibody as a risk factor for fluorouracil-induced drug eruptions showing acral erythema and discoidlupus-erythematosus-like lesions. dermatology (basel, switzerland). 2007;214(1):85-88. presented at winter clinical dermatology conference 2019 | hawaii | 18–23 jan 2019 durable improvement in patient reported outcomes across dlqi subdomains over 48 weeks in chronic plaque psoriasis patients treated with certolizumab pegol in two phase 3 trials (cimpasi-1 and cimpasi-2) a. blauvelt,1 r. b. warren,2 k. reich,3 m. boehnlein,4 s. kavanagh,5 m. lebwohl6 1oregon medical research center, portland, or; 2dermatology centre, salford royal nhs foundation trust, the university of manchester, uk; 3sciderm research institute, hamburg, and dermatologikum berlin, germany; 4ucb pharma, monheim, germany; 5ucb pharma, raleigh, nc; 6icahn school of medicine at mount sinai, new york, ny objective • to assess the impact of certolizumab pegol on dlqi subdomains over 48 weeks’ treatment in patients with moderate to severe plaque psoriasis. background • plaque psoriasis (pso) is an immune-mediated, inflammatory disease. • pso is associated with reduced health-related quality of life,1 with a higher disease burden reported in female patients.2 • certolizumab pegol (czp) is a unique, fc-free, pegylated, anti-tumor necrosis factor biologic, approved by both the fda and ema for the treatment of moderate to severe pso.3,4 • the clinical efficacy and safety of czp in pso has previously been reported, with durable improvements in signs and symptoms of disease over 48 weeks of treatment.5,6 • here, we report the impact of czp treatment on patient reported dermatology life quality index (dlqi) subdomains over 48 weeks. methods study design • patients enrolled in cimpasi-1 (nct02326298) and cimpasi-2 (nct02326272) received treatment according to the study diagram (figure 1). patients • ≥18 years of age with pso for ≥6 months with psoriasis area severity index (pasi) ≥12, ≥10% body surface area affected, physician’s global assessment ≥3 on a 5-point scale. • candidates for systemic pso therapy, phototherapy and/or photochemotherapy. • exclusion criteria: previous treatment with czp or >2 biologics; history of primary failure to any biologic or secondary failure to >1 biologic; erythrodermic, guttate or generalized pso types; history of current, chronic or recurrent viral, bacterial or fungal infections. conclusions • czp dosed at both 400 mg q2w and 200 mg q2w was effective at reducing dlqi scores over the first 16 weeks of treatment. • responses were durable over a further 32 weeks of treatment to week 48. • patients receiving czp 400 mg q2w consistently reported greater quality of life improvements across all subdomains. • at baseline, female patients reported a greater burden of disease for symptoms and feelings, personal relationships and daily activities, indicated by higher mean baseline scores. study assessments • dlqi subdomains were assessed through weeks 0–48: – symptoms and feelings (itchy/sore/painful stinging; embarrassed/ self-conscious) – daily activities (interference with shopping/home/garden; influence on clothes worn) – personal relationships (problems with partners/friends/relatives; any sexual difficulties) – leisure (affects social/leisure activities; makes it difficult to do any sports) – work and school (prevents or causes problems with work or studying) – treatment (how much of a problem is treatment) • dlqi response rates were defined as a score of 0 (response of ‘not at all’ or ‘not relevant’), indicating no impact of skin on that questionnaire item. statistical analyses • missing data were imputed as last observation carried forward (locf); patients who did not achieve at least a 50% improvement from baseline in pasi (pasi 50) at weeks 16, 32 or 40 had their week 16, 32 or 40 value carried forward to week 48. • dlqi response rates are the adjusted probabilities from a logistic regression model with factors for treatment group, region, study, prior biologic exposure, study x region, and study x prior biologic exposure. results patient disposition • 175, 186, and 100 patients were randomized to czp 400 mg every two weeks (q2w), czp 200 mg q2w or placebo q2w. • baseline demographics are shown in table 1. • at baseline, patients reported the greatest impact of disease on symptoms and feelings. work and school was least affected (table 2). • female patients reported higher baseline dlqi scores for symptoms and feelings, personal relationships and daily activities (table 2). dlqi mean score • dlqi mean score reduced through weeks 0–16 for czp-treated patients compared to placebo, across subdomains (figure 2). • dlqi mean score was maintained, or further improved, through weeks 16–48 for patients receiving czp (figure 2). • at week 48, the greatest change from baseline was reported in symptoms and feelings, followed by daily activities. • similar trends were also observed for leisure, work and school, and treatment. • change from baseline across all dlqi subdomains was similar between male and female patients. dlqi response rates • the largest improvements in response rate were observed for the subdomains shown in figure 3. however, similar trends were also reported for leisure, work and school, and treatment. aczp 200 mg q2w patients received czp 400 mg q2w at weeks 0, 2 and 4. bmi: body mass index; bsa: body surface area; czp: certolizumab pegol; dlqi: dermatology life quality index; il: interleukin; pasi: psoriasis area severity index; pga: physician’s global assessment; pso: plaque psoriasis; q2w: every two weeks; sd: standard deviation; tnf: tumor necrosis factor. table 1. demographics and baseline disease characteristics for all patients czp 400 mg q2w (n=175) czp 200 mg q2wa (n=186) placebo q2w (n=100) age, years, mean (sd) 45.0 (12.9) 45.6 (13.2) 45.7 (13.8) male, n (%) 103 (58.9) 125 (67.2) 61 (61.0) bmi, kg/m2, mean (sd) 31.2 (7.9) 32.0 (7.8) 31.2 (7.4) prior biologic use, n (%) 59 (33.7) 62 (33.3) 29 (29.0) anti-tnf 39 (22.3) 44 (23.7) 19 (19.0) anti-il-17 8 (4.6) 16 (8.6) 5 (5.0) anti-il-12/il-23 10 (5.7) 3 (1.6) 6 (6.0) pso duration, years, mean (sd) 18.5 (12.6) 17.7 (12.9) 17.0 (12.6) pasi, mean (sd) 19.6 (7.3) 19.2 (7.2) 18.6 (6.6) bsa affected, %, mean (sd) 23.6 (14.3) 23.5 (14.9) 23.1 (13.6) pga score, n (%) 3 (moderate) 126 (72.0) 128 (68.8) 72 (72.0) 4 (severe) 49 (28.0) 58 (31.2) 28 (28.0) dlqi, mean (sd) 13.7 (6.9) 14.2 (7.4) 13.4 (7.8) only nine placebo randomized patients continued to receive placebo in the maintenance period. czp: certolizumab pegol; ld: czp 400 mg loading dose at weeks 0, 2 and 4 or weeks 16, 18 and 20; pasi 50: ≥50% reduction from baseline in psoriasis area severity index; pasi 50–74: ≥50% but <75% reduction from baseline in psoriasis area severity index; q2w: every two weeks. figure 1. cimpasi-1 and cimpasi-2 study diagram czp 400 mg q2w czp 200 mg q2wa placebo q2w all patients (n=175) male (n=103) female (n=72) all patients (n=186) male (n=125) female (n=61) all patients (n=100) male (n=61) female (n=39) mean score (sd) symptoms and feelings 4.1 (1.4) 4.0 (1.3) 4.3 (1.5) 4.2 (1.5) 4.1 (1.6) 4.5 (1.4) 4.0 (1.5) 3.7 (1.4) 4.5 (1.6) daily activities 3.2 (1.7) 3.0 (1.6) 3.4 (1.8) 3.2 (1.9) 2.9 (1.9) 3.7 (1.7) 3.1 (1.8) 2.7 (1.8) 3.6 (1.6) leisure 2.4 (1.9) 2.4 (1.9) 2.5 (1.9) 2.7 (2.0) 2.5 (2.0) 2.9 (2.0) 2.5 (2.2) 2.1 (2.0) 2.9 (2.3) work and school 0.9 (1.0) 0.9 (0.9) 0.8 (1.0) 0.9 (1.0) 0.8 (1.0) 1.0 (1.1) 0.9 (1.1) 0.9 (1.0) 0.9 (1.1) personal relationships 1.9 (1.9) 1.8 (1.7) 2.0 (2.1) 2.0 (1.9) 1.9 (1.9) 2.2 (1.9) 1.8 (2.1) 1.7 (2.0) 2.0 (2.3) treatment 1.2 (1.1) 1.2 (1.0) 1.3 (1.1) 1.3 (1.1) 1.2 (1.1) 1.4 (1.1) 1.2 (1.0) 1.1 (1.1) 1.3 (1.0) table 2. baseline dlqi subdomain scores for male and female patients aczp 200 mg q2w patients received czp 400 mg q2w at weeks 0, 2 and 4. lower scores indicate greater quality of life. symptoms and feelings: itchy/sore/painful stinging; embarrassed/self-conscious. daily activities: interference with shopping/home/garden; influences clothes worn. leisure: affects social/leisure activities; makes it difficult to do any sports. personal relationships: problems with partners/friends/relatives; any sexual difficulties. treatment: how much of a problem is treatment. czp: certolizumab pegol; dlqi: dermatology life quality index; q2w: every two weeks; sd: standard deviation. figure 2. dlqi subdomain mean scores through weeks 0–48 for male and female patients locf imputation. lower scores indicate greater quality of life. aczp 200 mg q2w patients received czp 400 mg q2w at weeks 0, 2 and 4. czp: certolizumab pegol; dlqi: dermatology life quality index; q2w: every two weeks; sd: standard deviation. figure 3. response rates for dlqi subdomains at weeks 16 and 48 for all patients logistic regression with locf imputation. dlqi response rates were defined as a score of 0 (response of ‘not at all’ or ‘not relevant’), indicating no impact of skin on that questionnaire item. higher scores indicate greater quality of life. czp: certolizumab pegol; dlqi: dermatology life quality index; q2w: every two weeks. czp 400 mg q2w czp 200 mg q2wa placebo q2w week 16 male 1.1 (1.1) 1.4 (1.4) 3.0 (1.6) female 1.6 (1.6) 1.6 (1.4) 3.7 (1.5) all patients 1.3 (1.4) 1.4 (1.4) 3.3 (1.6) week 48 male 0.9 (1.2) 1.5 (1.7) female 1.6 (1.8) 1.7 (1.7) all patients 1.2 (1.5) 1.6 (1.7) czp 400 mg q2w czp 200 mg q2wa placebo q2w week 16 male 0.6 (1.1) 0.8 (1.3) 1.9 (1.6) female 1.1 (1.7) 1.0 (1.2) 2.8 (1.3) all patients 0.8 (1.4) 0.8 (1.3) 2.2 (1.6) week 48 male 0.4 (0.8) 0.9 (1.5) female 1.2 (1.8) 1.1 (1.4) all patients 0.7 (1.4) 1.0 (1.4) czp 400 mg q2w czp 200 mg q2wa placebo q2w week 16 male 0.6 (1.3) 0.7 (1.4) 1.6 (2.0) female 0.7 (1.5) 0.7 (1.3) 1.8 (1.7) all patients 0.6 (1.4) 0.7 (1.3) 1.7 (1.9) week 48 male 0.3 (1.0) 0.7 (1.4) female 0.7 (1.7) 0.7 (1.3) all patients 0.5 (1.3) 0.7 (1.4) b) daily activities c) personal relationships 5 m e a n s c o re week 4 3 2 1 0 0 12 1682 24 32 0 12 1682 24 32 12 1682 24 3248 5 m e a n s c o re week 4 3 2 1 0 0 48 5 m e a n s c o re week 4 3 2 1 0 0 48 a) symptoms and feelings male (n=103) female (n=72) czp 400 mg q2w (n=175) male (n=125) female (n=61) czp 200 mg q2w (n=186) male (n=61) female (n=39) placebo q2w (n=100) mean score (sd) mean score (sd) mean score (sd) 90 80 70 60 50 40 30 10 20 100 0 d lq i re sp o n se r at e ( % ) week 48week 16 a) symptoms and feelings 32.0% 28.0% 45.7% 33.3% b) daily activities 64.6% 57.5% 68.6% 57.5% c) personal relationships 77.1% 69.4% 84.6% 71.0% czp 400 mg q2w (n=175) czp 200 mg q2w (n=186) 90 80 70 60 50 40 30 10 20 100 0 d lq i re sp o n se r at e ( % ) week 48week 16 90 80 70 60 50 40 30 10 20 100 0 d lq i re sp o n se r at e ( % ) week 48week 16 0week 16 484032 initial treatment period (double-blind) screening maintenance period (double-blind) <pasi 50 entered escape arm (czp 400 mg q2w) placebo q2w pasi 50–74 received ld then czp 200 mg q2w czp 200 mg q2w czp 400 mg q2w ld <pasi 50 withdrawn <pasi 50 withdrawn <pasi 50 withdrawn n=100 n=186 n=175 1:2:2 randomization references: 1. kimball ab. et al. j eur acad dermatol venereol 2010;24:989–1004; 2. lesuis n. et al. bmc medicine 2012;10:82. available at: http://www.biomedcentral.com/1741-7015/10/82; 3. certolizumab pegol prescribing information. available at http://www.accessdata.fda.gov; 4. certolizumab pegol summary of product characteristics. available at http://www.ema.europa.eu/ema; 5. gottlieb ab. et al. j am acad dermatol 2018;79:302–14.e6; 6. lebwohl m. et al. j am acad dermatol 2018;79:266–76.e5. author contributions: substantial contributions to study conception/design, or acquisition/analysis/interpretation of data: ab, rbw, kr, mb, sk, ml; drafting of the publication, or revising it critically for important intellectual content: ab, rbw, kr, mb, sk, ml; final approval of the publication: ab, rbw, kr, mb, sk, ml. author disclosures: ab: abbvie, aclaris, akros, allergan, almirall, amgen, arena, boehringer ingelheim, celgene, dermavant, dermira, inc., eli lilly and company, galderma, genentech/roche, glaxosmithkline, janssen, leo, meiji, merck sharp & dohme, novartis, pfizer, purdue pharma, regeneron, revance, sandoz, sanofi genzyme, sienna pharmaceuticals, sun pharma, ucb pharma, valeant, vidac; rbw: abbvie, almirall, amgen, boehringer ingelheim, celgene, janssen, lilly, leo pharma, novartis, pfizer, sanofi, ucb pharma, xenoport; kr: abbvie, affibody, amgen, biogen, boehringer ingelheim, celgene, centocor, covagen, forward pharma, glaxosmithkline, janssen-cilag, kyowa kirin, leo pharma, eli lilly, medac, merck sharp & dohme corp., novartis, ocean pharma, pfizer, regeneron, samsung biopepis, sanofi, takeda, ucb pharma, valeant, xenoport; mb, sk: employees of ucb pharma; ml: allergan, aqua, leo pharma, promius. employee of mount sinai which receives research funds from abbvie, amgen, boehringer ingelheim, celgene, eli lilly, janssen/johnson & johnson, kadmon, medimmune/astra zeneca, novartis, pfizer, valeant, vidac. acknowledgements: the studies were funded by dermira inc. in collaboration with ucb pharma. ucb is the regulatory sponsor of certolizumab pegol in psoriasis. we thank the patients and their caregivers in addition to the investigators and their teams who contributed to this study. the authors acknowledge bartosz łukowski, msc, ucb pharma, brussels, belgium for publication coordination and amelia frizell-armitage, phd, costello medical, cambridge, uk for medical writing and editorial assistance. all costs associated with development of this poster were funded by ucb pharma. summary we evaluated patient reported outcomes across dlqi subdomains for patients receiving certolizumab pegol dosed at 400 mg or 200 mg every two weeks for one year. after one year (48 weeks) of treatment with czp 400 mg or 200 mg dosed every two weeks, mean dlqi score was improved by... certolizumab pegol rapidly reduced dlqi score across subdomains and response was durable to week 48. daily activities 78% 69% personal relationships 74% 65% symptoms and feelings 73% 62% certolizumab pegol (czp) 1 fab’ ecztra 1 (n=603) and ecztra 2 (n=593) ecztra 1 (n=199) and ecztra 2 (n=201) tralokinumab 300 mg q2w placebo q2w 3:1 randomization 16 weeks0 patients with clinical response iga-0/1 or easi-75 –6 weeks initial treatmentscreening maintenance treatmenta key inclusion criteria • diagnosis of atopic dermatitis for �1 year • bsa involvement �10% • easi score �12 at screening and 16 at baseline • iga score �3 at screening and at baseline • worst daily pruritus nrs weekly average score �4 prior to baseline primary endpoints • iga-0/1 at week 16 • easi-75 at week 16 sleep measures assessed up to week 16 • nrs for eczema-related sleep interference • scorad sleep score • poem sleep score figure 1. ecztra 1 and 2 trial design introduction methods objective ● to assess the effect of tralokinumab monotherapy on sleep loss in patients with moderate-to-severe atopic dermatitis from the ecztra 1 and ecztra 2 trials during the initial 16-week treatment period specifically targeting interleukin-13 with tralokinumab improved sleep in two phase 3, randomized, double-blind, placebo-controlled trials in patients with atopic dermatitis jonathan i. silverberg,1 sébastien barbarot,2 melinda gooderham,3 jan c. simon,4 eric simpson,5 azra kurbasic,6 christina kurre olsen,6 michael j. cork7 1department of dermatology, the george washington university school of medicine and health sciences, washington, dc, usa; 2department of dermatology, chu, nantes, france; 3skin centre for dermatology, peterborough, ontario, canada; 4department of dermatology, venereology and allergology, university medical center, leipzig, germany; 5department of dermatology, oregon health & science university, portland, or, usa; 6leo pharma a/s, ballerup, denmark; 7sheffield dermatology research, department of infection, immunity and cardiovascular disease, the university of sheffield, sheffield, uk 0.0 tralokinumab q2w (n=601) placebo (n=197) –0.5 –1.0 c h a n g e in s le e p n r s (9 5% c i) –1.5 –2.0 –2.5 –3.0 0.0 –0.5 –1.0 –1.5 –2.0 –2.5 –3.0 0 1 2 3 4 5 6 7 8 week 9 10 11 12 13 14 1615 1 2 3 4 5 6 7 8 9 10 11 12 13 14 16150 week 16 tralokinumab q2w (n=591) placebo (n=201) a b c h a n g e in s le e p n r s (9 5% c i) –2.6 –1.5 –2.9 –1.9 *** ** *** *** *** *** *** *** *** *** ** ** ** ** ** ** *** *** *** *** *** *** *** *** *** *** *** *** *** *** *** *** ecztra 1 ecztra 2 figure 2. change in eczema-related sleep nrs in (a) ecztra 1 and (b) ecztra 2 by week during the initial treatment period 100 80 p a ti e n ts , % 60 40 20 0 ecztra 1baseline week 16 a placebo (n=197) tralokinumab 300 mg q2w (n=601) placebo (n=197) tralokinumab 300 mg q2w (n=601) every day 5–6 days 3–4 days 1–2 days no days sleep disturbance 100 80 p a ti e n ts , % 60 40 20 0 ecztra 2baseline week 16 b placebo (n=201) tralokinumab 300 mg q2w (n=591) placebo (n=201) tralokinumab 300 mg q2w (n=591) every day 5–6 days 3–4 days 1–2 days no days sleep disturbance 33.3% 10.9% 16.7% 19.1% 20% 51.5% 17% 10% 10.5% 11% 65.4% 14% 10.4% 8% 68% 11% 8.5% 10.5% 36.8% 11.4% 16% 19.4% 16.5% 51.6% 13.9% 15.5% 11.9% 7.2% 63.7% 12.6% 12.7% 7.8% 62.9% 15.5% 14.4% 5.7% figure 4. poem sleep scores at baseline and week 16 in (a) ecztra 1 and (b) ecztra 2 sleep measure scale collected nrs for eczema-related sleep interference (24-hour recall) 11-point numeric scale of the extent to which eczema interfered with sleep the last night 0 = “did not interfere” to 10 = “completely interfered” daily via ediary by patients scorad sleep score (3-day recall) visual analog scale of average sleeplessness over the last 3 days/nights 0 = “no sleeplessness” to 10 = “worst imaginable sleeplessness” at biweekly visits poem sleep score (7-day recall) 5-point categorical scale of the frequency of sleep disturbance in the previous week 0 = “no days” to 4 = “every day” electronically at biweekly visits up to week 8, then weeks 12 and 16 table 1. patient-reported sleep measures assessed during the initial 16-week treatment period e c z t r a 1 ( n = 8 0 2 ) e c z t r a 2 ( n =7 9 4 ) p l a c e b o ( n = 1 9 9 ) tr a l o k i n u m a b q 2 w ( n = 6 0 3 ) p l a c e b o ( n = 2 0 1 ) tr a l o k i n u m a b q 2 w ( n = 593 ) mean age, years 39 39 35 37 male, n (%) 123 (62) 351 (58) 114 (57) 359 (61) mean duration of atopic dermatitis, years 29.6 27.9 27.5 28.3 mean bsa involvement with atopic dermatitis, % 54.2 52.7 53.0 52.6 severe disease (iga-4), % 51.3 50.6 50.2 48.2 mean easi 32.9 32.2 32.6 32.1 mean weekly average eczema-related sleep nrs 6.8 6.9 7.3 7.2 mean scorad sleep score 6.4 6.5 7.2 7.0 mean poem sleep score 3.3 3.3 3.3 3.3 table 2. patient demographics and baseline characteristics at baseline 0.0 tralokinumab q2w (n=601) placebo (n=197) –1.0 c h a n g e in s c o r a d s le e p s co re (9 5% c i) –2.0 –3.0 –4.0 –1.0 –2.0 –3.0 –4.0 –5.0 0.0 –5.0 0 2 4 6 8 week 10 12 14 2 4 6 8 10 12 14 16 0 week ecztra 1 ecztra 2 16 tralokinumab q2w (n=591) placebo (n=201) a b c h a n g e in s c o r a d s le e p s co re (9 5% c i) –2.6 –1.8 –3.0 –1.8 *** *** *** *** *** *** *** *** *** *** *** *** * ** ** ** figure 3. change in scorad sleep score in (a) ecztra 1 and (b) ecztra 2 by week during the initial treatment period *p<0.05 versus placebo; **p<0.01 versus placebo; ***p<0.001 versus placebo. data collected after permanent discontinuation of the imp or initiation of rescue medication not included. in case of no post-baseline assessment before initiation of rescue medication, the week 2 change was imputed as 0. repeated measurements model: change = treatment*week + baseline*week + region + baseline iga. **p<0.01 versus placebo; ***p<0.001 versus placebo. data collected after permanent discontinuation of the imp or initiation of rescue medication not included. in case of no post-baseline assessment before initiation of rescue medication, the week 2 change was imputed as 0. repeated measurements model: change = treatment*week + baseline*week + region + baseline iga. data collected after permanent discontinuation of imp or initiation of rescue medication not included. missing data at week 16 imputed using the locf, i.e. last observation of poem sleep score prior to permanent discontinuation of the imp or initiation of rescue medication was carried forward. results disclosures jonathan i. silverberg reports honoraria as a consultant/advisory board member from leo pharma and has acted as a consultant for, and/or received grants/honoraria from, abbvie, anaptysbio, asana biosciences, galderma research and development, glaxosmithkline, glenmark, kiniksa, leo pharma, lilly, medimmune, menlo therapeutics, pfizer, puricore, regeneron, and sanofi. sébastien barbarot has received research grants, personal fees, and non-financial support from abbvie, bioderma, pierre fabre laboratory, fondation pour la dermatite atopique, janssens, laboratoire la roche posay, leo pharma, novartis, and sanofi-genzyme. melinda gooderham has been an investigator, consultant, and/or speaker for abbvie, amgen, boehringer ingelheim, celgene, coherus, dermira, galderma, gsk, janssen, leo pharma, lilly medimmune, merck serono, novartis, regeneron, roche, sanofi genzyme, takeda, ucb, pfizer, and valeant. jan c. simon has received speaker’s honoraria and is member of advisory boards of abbvie pharma, janssen pharma, novartis pharma, and ucb pharma, and received travel grants from these companies and from leo pharma. eric simpson reports grants and personal fees from abbvie, lilly, leo pharma, medimmune, pfizer, and regeneron; grants from celgene, galderma, kyowa hakko kirin, merck, novartis, and tioga; and personal fees from boehringer ingelheim, dermavant, dermira, fortébio, incyte, menlo therapeutics, ortho dermatologics, pierre fabre, sanofi, and valeant. azra kurbasic and christina kurre olsen are employees of leo pharma. michael j. cork is an investigator and/or consultant for astellas, boots, dermavant, galapagos, galderma, hyphens, johnson & johnson, leo pharma, l’oréal, menlo therapeutics, novartis, oxagen, pfizer, procter & gamble, reckitt benckiser, regeneron, and sanofi genzyme. the ecztra 1 and 2 studies were sponsored by leo pharma a/s, ballerup, denmark. references 1. weidinger s, novak n. lancet 2016; 387: 1109–1122. 2. silverberg ji et al. ann allergy asthma immunol 2018; 121: 340–347. 3. dalgard fj et al. j invest dermatol 2015; 135: 984–991. 4. chang y, chiang b. j allergy clin immunol 2018; 142: 1033−1040. 5. silverberg ji et al. j invest dermatol 2015; 135: 56−66. 6. jeon c et al. dermatol ther (heidelb) 2017; 7: 249−264. 7. bieber t. allergy 2020; 75: 54−62. 8. tsoi lc et al. j invest dermatol 2019; 139: 1480−1489. 9. popovic b et al. j mol biol 2017; 429: 208−219. 10. simpson e et al. presented at the american academy of dermatology annual meeting, march 20–24, 2020, denver, co, usa. 11. lei d et al. ann allergy asthma immunol 2020; 124: 261−266. ● atopic dermatitis is a chronic inflammatory skin disease that is associated with sleep loss and impaired quality of life1-3 ● several factors may contribute to sleep loss in atopic dermatitis, including pruritus, scratching, and dysregulated cytokine levels4-6 ● tralokinumab is a fully human, immunoglobulin g4 monoclonal antibody that specifically binds to the il-13 cytokine with high affinity, preventing interaction with the il-13 receptor and subsequent downstream il-13 signaling, thus preventing its pro-inflammatory activity7-9 ● in phase 3 trials, ecztra 1 (nct03131648) and ecztra 2 (nct03160885), investigating tralokinumab monotherapy in adults with moderate-to-severe atopic dermatitis, significantly more patients receiving tralokinumab monotherapy achieved the primary endpoints of investigator global assessment of 0 or 1 (iga-0/1) [clear or almost clear skin] and 75% improvement in eczema area and severity index (easi-75) compared with placebo at week 16 of the initial treatment period10 study design and patients ● ecztra 1 and 2 were identically designed, randomized, double-blind, placebo-controlled, multinational, 52-week trials of tralokinumab monotherapy in patients with moderate-to-severe atopic dermatitis ● eligible patients were ≥18 years of age with a confirmed diagnosis of atopic dermatitis for ≥1 year and were candidates for systemic therapy due to a recent (within 1 year) history of inadequate response or intolerance to topical treatment. additional eligibility criteria included an easi score of ≥16, iga ≥3, and worst daily pruritus numeric rating scale (nrs) ≥4 ● patients were randomized 3:1 to receive either subcutaneous tralokinumab 300mg or placebo every 2 weeks for an initial treatment period of 16 weeks (figure 1) afull design of treatment regime after week 16 not shown. bsa, body surface area; q2w, every 2 weeks. measures of sleep ● scoring atopic dermatitis (scorad) and patient-oriented eczema measure (poem) sleep scores were recently validated for use as single-item, patient-reported assessments of sleep loss in adults with atopic dermatitis11 ● several measures of sleep were assessed in ecztra 1 and 2 during the initial 16-week treatment period (table 1): — nrs for eczema-related sleep interference — scorad sleep score — poem sleep score statistical analysis ● changes in eczema-related sleep interference nrs and scorad sleep score were assessed by a repeated measurements model, including baseline iga, region, and treatment-by-week interactions as factors and interaction between week and baseline value as covariates — change = treatment*week + baseline*week + region + baseline iga ● the percentage of patients in each of the five poem sleep score categories was assessed at baseline and week 16 — missing data at week 16 was imputed using last observation carried forward (locf), whereby the last observation of poem sleep score prior to permanent discontinuation of the investigational medicinal product (imp) or initiation of rescue medication was carried forward ● data collected after permanent discontinuation of the imp or initiation of rescue medication were excluded from the analyses patient characteristics ● in total, 802 and 794 patients were randomized in ecztra 1 and 2, respectively (table 2) ● overall, baseline characteristics were similar across both trials eczema-related sleep interference nrs ● there was a greater improvement in weekly average eczema-related sleep interference nrs with tralokinumab compared with placebo in both ecztra 1 and ecztra 2 (figure 2) — change from baseline in eczema-related sleep interference nrs was larger with tralokinumab compared with placebo at each week, with separation observed between the treatment groups (p0.001) from week 1 ● the least-square mean (lsm) change from baseline at week 16 was greater with tralokinumab compared with placebo in both trials (ecztra 1, –2.6 [95% confidence interval (ci) –2.9, –2.4] vs –1.9 [95% ci –2.4, –1.5]; p=0.007, and ecztra 2, –2.9 [95% ci –3.1, –2.7] vs –1.5 [95% ci –1.9, –1.1]; p0.001) scorad sleep score ● there was a greater improvement in scorad sleep score with tralokinumab compared with placebo in both ecztra 1 and ecztra 2 (figure 3) — change from baseline in scorad sleep score was greater with tralokinumab compared with placebo, with separation observed between the treatment groups from week 2 (p0.001) and at each week onwards (p0.05) ● the lsm change from baseline at week 16 was greater with tralokinumab compared with placebo (ecztra 1, −2.6 [95% ci –2.9, –2.3] vs –1.8 [95% ci –2.3, –1.3]; p=0.004, and ecztra 2, –3.0 [95% ci –3.2, –2.7] vs –1.8 [95% ci –2.3, –1.2]; p0.001) poem sleep score ● there was a greater shift towards lower poem sleep scores with tralokinumab compared with placebo in both ecztra 1 and ecztra 2 (figure 4) — the majority of patients (87.5−92.8%) across treatment groups reported ≥3 nights of sleep disturbance at baseline in both trials — at week 16, 64.2% and 60.9% of tralokinumab-treated patients reported ≥3 nights of sleep disturbance compared to 81% and 78.5% of patients with placebo ● a greater proportion of tralokinumab-treated patients (35.9−39.1%) reported “no days” or “1−2 days” of sleep disturbance at week 16 versus placebo (19.1−21.5%) winter clinical dermatology conference, january 16-24, 2021 conclusions ● tralokinumab monotherapy 300 mg every 2 weeks demonstrated improvements compared with placebo in three sleep measures (nrs for eczema-related sleep interference, scorad sleep score, and poem sleep score) during the initial 16-week treatment period ● improvement in sleep measures was consistent across two large phase 3 trials, ecztra 1 and ecztra 2 ● a greater proportion of tralokinumab-treated patients reported either “no days” or “1–2 days” of sleep disturbance ● early improvement in sleep measures as early as week 1 with tralokinumab is consistent with its effects on the signs and troublesome symptoms of atopic dermatitis, including pruritus 20201210_delrosso_phase 3 efficacy and safety efficacy and safety of microencapsulated benzoyl peroxide 3% and microencapsulated tretinoin 0.1% (e-bpo/e-atra) in acne vulgaris: results from two randomized controlled clinical trials del rosso j1, sugarman j2, levy-hacham o3, mizrahi r3 1. jdr research, las vegas, nv. 2. university of california san francisco, san francisco, ca. 3. sol-gel technologies ltd, ness ziona, israel. methods design results patients • in study 65-04, 281 patients were randomized to e-bpo/e-atra and 143 to vehicle; 249 (88.6%) and 131 (91.6%) completed the trial. in study 65-05, 290 patients were randomized to e-bpo/e-atra and 144 to vehicle; 242 (83.4%) and 131 (91.6%) completed the trial. baseline patient characteristics were balanced across groups in both trials (table 1) safety • nearly all aes were mild or moderate in severity. • a total of 18 subjects discontinued from studies 65-04 and 65-05 due to a treatment-emergent ae: 18 (2%) in e-bpo/e-atra and 0 in vehicle. • no treatment-related serious aes (saes) were identified in either study. • 2 subjects reported saes in study 65-05; (1) e-bpo/e-atra subject reported depression. • prospective evaluations indicated very good skin tolerability for e-bpo/e-atra (table 2). conclusions e-bpo/e-atra successfully met all primary efficacy endpoints demonstrating statistically significant improvements over vehicle. there were no treatment-related saes. e-bpo/e-atra was well tolerated, with results similar to vehicle at 12 weeks. efficacy iga • in each of the two trials, e-bpo/e-atra was significantly superior to vehicle for the percentage of patients achieving iga success (figures 2 and 3). lesions • results from both trials indicated that e-bpo/e-atra was significantly superior to vehicle for decreasing the number of inflammatory lesions (figure 4) and non-inflammatory lesions (figure 5) from baseline at week 12. endpoints co-primary efficacy endpoints • proportion of patients who achieved a two-grade reduction from baseline and grade 0 (clear) or grade 1 (almost clear) at week 12 on a 5-point iga scale. • absolute change in inflammatory lesion counts from baseline at week 12. • absolute change in non-inflammatory lesion counts from baseline at week 12. safety endpoints • safety was assessed through cutaneous safety assessment, local tolerability assessment, adverse event (ae) reporting, physical examination, and vital signs. data analysis • all efficacy analyses were carried out using the intent-to-treat population. safety analyses were carried out using the safety population. figure 1. study design introduction • benzoyl peroxide (bpo) is recommended for treatment of acne of all severities.1 it is bactericidal against c. acnes on the skin and within hair follicles with no risk for development of resistance,1,2 and it also has sebostatic and keratolytic effects.3 • bpo is widely used as a single agent in many different vehicles,4 and in combination with other medications.3,5 multiple analyses have indicated that the efficacy of bpo is enhanced when used in combination with topical retinoids, such as tretinoin (atra).6,7 however, bpo causes degradation of tretinoin, reducing its effectiveness.8 • bpo and atra can also result in significant skin irritation when applied to the face of patients with acne,9,10 and there is some evidence suggesting that their irritative effects may be additive.11 • e-bpo/e-atra is an investigational, antibiotic-free, fixed-dose combination of microencapsulated tretinoin 0.1% and microencapsulated bpo 3% cream. the use of sol-gel’s microencapsulation technology platform provides a stable combination of bpo and atra, extending drug delivery time, and reducing potential irritation caused by direct application of the drugs to the skin. • two multicenter, randomized, double-blind, parallel-group vehicle-controlled trials (sgt-65-04 and sgt-65-05) carried out at 63 sites across the united states (figure 1). acknowledgments: the authors gratefully acknowledge the editorial and data analysis contributions of robert rhoades, phdand thomas prunty, cmpp of aramed strategies whose assistance was funded by sol-gel technologies, ltd. references: 1. zaenglein al, et al. j am acad dermatol. 2016;74:945-973 e933; 2. walsh tr, et al. lancet infect dis.2016;16:e23-33; 3. matin t, goodman mb. 2019. available from http://www.ncbi.nlm.nih.gov/books/ nbk537220/; 4. kawashima m, et al. jdermatol. 2017;44:1212-1218; 5. kircik lh. j drugs dermatol. 2013;12:s73-76; 6. sagransky m, et al. expert opin pharmacother. 2009;10:2555-2562; 7. fakhouri t, et al. j drugs dermatol. 2009;8:657-661; 8. martin b, et al. br j dermatol. 1998;139 (suppl 52):8-11; 9. patel vb, et al. drug dev ind pharm. 2001;27:863-869; 10. quigley jw, bucks da. j am acad dermatol. 1998;38:s5-10; 11. brand b, et al. j am acad dermatol. 2003;49 (3 suppl):s227-232. table 1. baseline patient characteristics study 65-04 study 65-05 e-bpo/e-atra (n=281) vehicle (n=143) e-bpo/e-atra (n=290) vehicle (n=144) 20.9 (8.48) 18.0 (11-67) 106 (37.7%) 175 (62.3%) 102 (36.3%) 178 (63.3%) 1 (0.4%) 251 (89.3%) 30 (10.7%) 33.5 (14.62) 28.0 (20-97) 48.6 (20.24) 42.0 (30-148) 21.4 (8.62) 18.0 (10-57) 20.1 (6.96) 18.0 (10-51) 117 (40.3%) 173 (59.7%) 85 (29.3%) 204 (70.3%) 1 (0.3%) 262 (90.3%) 28 (9.7%) 28.2 (8.70) 25.0 (20-62) 44.6 (18.03) 39.0 (23-149) 20.3 (6.67) 18.5 (9-42) 60 (42.0%) 83 (58.0%) 67 (46.5%) 77 (53.5%) 44 (30.8%) 98 (68.5%) 1 (0.7%) 56 (38.9%) 87 (60.4%) 1 (0.7%) 132 (92.3%) 11 (7.7%) 133 (93.0%) 10 (7.0%) 33.5 (14.69) 78 0 (20-90) 27.5 (8.52) 75 (20-75) 47.1 (19.97) 41.0 (30-140) 44.9 (18.82) 38.0 (30-123) age, years mean (sd) median (range sex, n (%) male female ethnicity, n (%) hispanic/latino not hispanic or latino unknown/not reported iga severity moderate severe inflammatory lesion count mean (sd) median (range) non-inflammatory lesion count mean (sd) median (range) number of sites 32 31 • age ≥ 9 years • ≥20 to ≤100 inflammatory lesions • ≥30 to ≤150 non-inflammatory lesions • iga grade 3 (moderate) or grade 4 (severe) • cysts/nodules ≤ 2 in cl us io n cr ite ri a randomization baseline 2 4 weeks 8 12 12 weeks of treatment 63 total sites study 65 04: 424 study 65-05: 434 qd, self-applied vehicle cream e-bpo/e-atra cream (3% e-bpo, 0.1% e-atra) 2:1 e-atra, microencapsulated tretinoin; e-bpo, microencapsulated benzoyl peroxide; iga, investigator’s global assessment; qd, once daily. to interact with and explore these data more intimately, please click here: https://www.solgelposters.com 38.5% 11.5% 0% 10% 20% 30% 40% p er ce nt o f s ub je ct s ac hi ev in gi g a su cc es s at w ee k 12 e-bpo/e-atra(n=281) e-bpo/e-atra(n=290)vehicle(n=143) 25.4% 14.7% 0% 10% 20% 30% 40% study 65-05 vehicle(n=144) figure 2. success in iga at week 12 p<0.001 study 65-04 erythema scaling pigmentation dryness itching burning stinging study 65-05 erythema scaling pigmentation dryness itching burning stinging 62.0% 78.8% 61.6% 71.2% 86.0% 92.4% 92.4% 57.8% 83.2% 70.5% 73.0% 88.1% 91.4% 96.7% 33.2% 19.6% 32.8% 22.0% 12.8% 6.0% 7.2% 32.8% 13.1% 21.7% 22.5% 9.4% 5.7% 3.3% 4.4% 1.6% 4.8% 6.0% 1.2% 1.6% 0.4% 9.4% 3.7% 7.8% 4.5% 2.5% 2.9% 0.0% 0.4% 0 0.8% 0.8% 0 0 0 0 0 0 0 0 0 0 65.9% 83.3% 67.4% 78.0% 89.4% 95.5% 94.7% 64.4% 89.4% 70.5% 84.1% 87.9% 96.2% 99.2% 25.8% 15.9% 27.3% 18.9% 7.6% 3.8% 3.8% 28.0% 9.8% 25.8% 14.4% 9.8% 30% 0.0% 8.3% 0.8% 5.3% 3.0% 3.0% 0.8% 1.5% 7.6% 0.8% 3.8% 1.5% 2.3% 0.8% 0.8% 0 0 0 0 0 0 0 0 0 0 0 0 0 0 none mi l d moderate severe none mi l d moderate severe e-bpo/e-atra (n=274) % vehicle (n=139) % table 2. skin tolerability for e-bpo/e-atra and vehicle -21.6 -14.8 -25 -15 -5 m ea n re du ct io n in in fla m m at or y le si on co un t fr om b as el in e at w ee k1 2 vehicle (n=143) study 65-04 e-bpo/e-atra(n=281) -14.1 -16.2 p=0.018 -25 -15 -5 study 65-05 e-bpo/e-atra(n=290) vehicle (n=144) figure 4. reduction in inflammatory lesion count at week 12 2x trials / 12 weeks / 63 sites acrossus -29.7 -19.8 -35 -25 -15 -5 m ea n re du ct io n in n on -in fla m m at or y le si on c ou nt fr om b as el in e at w ee k1 2 study 65-04 e-bpo/e-atra(n=281) vehicle (n=143) -24.2 -17.4 -35 -25 -15 -5 study 65-05 e-bpo/e-atra(n=290) vehicle (n=144) figure 5. reduction in non-inflammatory lesion count at week 12 figure 3. improvement in iga and reduction in lesion count with e-bpo/e-atra subject: age: 18 years old. gender: female. although this patient did not achieve success as defined by the trial protocol, this represents a real-world clinical success and the authors note the improvement is unusual for topical monotherapy baseline week 12 subject: age: 19 years old. gender: male. race: hispanic or latino. baseline week 12 lesions count 50 4 study 65-04 p=0.017 p<0.001 p<0.001 p<0.001 http://www.ncbi.nlm.nih.gov/books/ efficacy and safety of microencapsulated benzoyl peroxide 3% and microencapsulated tretinoin 0.1% (e-bpo/e-atra) in acne vulgaris: results from two randomized controlled clinical trials deucravacitinib, an oral, selective tyrosine kinase 2 (tyk2) inhibitor, versus placebo and apremilast in moderate to severe plaque psoriasis: onset of action in the phase 3 poetyk pso-1 and poetyk pso-2 trials neil j korman,1 kim papp,2 jerry bagel,3 peter foley,4 akimichi morita,5 subhashis banerjee,6 elizabeth colston,6 tao wang,6 john throup,6 diamant thaçi7 1case western reserve university and university hospitals, cleveland, oh, usa; 2clinical research and probity medical research, waterloo, on, canada; 3windsor dermatology, east windsor, nj, usa; 4skin health institute, carlton, vic, australia; 5nagoya city university, graduate school of medical sciences, nagoya, japan; 6bristol myers squibb, princeton, nj, usa; 7university of lübeck, lübeck, germany introduction • deucravacitinib — novel, oral, selective tyrosine kinase 2 (tyk2) inhibitor with a unique mechanism of action distinct from janus kinase (jak) 1/2/3 inhibitors1 • binds to the tyk2 regulatory domain with high selectivity and inhibits tyk2 via an allosteric mechanism (figure 1)1 — ≥100-fold greater selectivity for tyk2 vs jak 1/3 and ≥2000-fold greater selectivity for tyk2 vs jak 21,2 • inhibits tyk2-mediated signaling of cytokines involved in psoriasis pathogenesis (eg, interleukin 23 [il-23], il-12, and type i interferons)1 — previously demonstrated good efficacy and tolerability in phase 2 trials in moderate to severe plaque psoriasis3 and in active psoriatic arthritis4 figure 1. mechanism of action of deucravacitinib deucravacitinib (allosteric inhibitor) regulatory domain catalytic domain atp-binding active site (other kinase inhibitors) tyk2 atp, adenosine triphosphate; tyk2, tyrosine kinase 2. objective • to assess the onset of action of deucravacitinib using data from the phase 3 poetyk pso-1 and pso-2 trials methods study designs • poetyk pso-1 (nct03624127) and pso-2 (nct03611751) were double-blind, placebocontrolled, 52-week trials that randomized patients with moderate to severe plaque psoriasis (body surface area [bsa] involvement ≥10%, psoriasis area and severity index [pasi] ≥12, static physician’s global assessment [spga] score ≥3) 1:2:1 to placebo, deucravacitinib 6 mg once daily, or apremilast 30 mg twice daily (figure 2) — patients were stratified by geographic region, body weight, and prior biologic use — patients receiving placebo switched to deucravacitinib at week 16 and patients receiving apremilast failing to meet study-specific efficacy thresholds (≥50% reduction from baseline in pasi [pasi 50] score in pso-1, ≥75% reduction from baseline in pasi [pasi 75] score in pso-2) switched to deucravacitinib at week 24 • coprimary endpoints were the proportion of patients who achieved pasi 75 and spga score of 0 or 1 (0/1) responses vs placebo at week 16 figure 2. study designs poetyk pso-1 (n=666) poetyk pso-2 (n=1020) deucravacitinib 6 mg qdplacebo (n=166) deucravacitinib 6 mg qd<pasi 50 apremilast 30 mg bidpasi 50 titrate*1 :2 :1 r an d om iz at io n weeks 16 24 520 deucravacitinib 6 mg qdplacebo (n=255) deucravacitinib 6 mg qd (n=511) deucravacitinib 6 mg qd<pasi 75 deucravacitinib 6 mg qd<pasi 75 deucravacitinib 6 mg qd deucravacitinib 6 mg qd placebob pasi 75 apremilast 30 mg bida (n=254) pasi 751 :2 :1 r an d om iz at io n weeks 16 24 520 1:1 deucravacitinib 6 mg qdplacebob deucravacitinib 6 mg qd (n=332) primary endpoint primary endpoint apremilast 30 mg bida (n=168) aapremilast was titrated from 10 mg qd to 30 mg bid over the first 5 days of dosing. bupon relapse (≥50% loss of week 24 pasi percentage improvement from baseline), patients were to be switched to deucravacitinib 6 mg qd. bid, twice daily; pasi 50, ≥50% reduction from baseline in psoriasis area and severity index; pasi 75, ≥75% reduction from baseline in pasi; qd, once daily. efficacy analyses • onset of action of deucravacitinib was evaluated by: — determining mean change from baseline or percentage change from baseline, adjusted for baseline covariates, in continuous objective and patient-reported efficacy outcomes that are sensitive to change — endpoints analyzed included pasi, bsa, spga×bsa, psoriasis symptoms and signs diary (pssd) symptom score, and dermatology life quality index (dlqi) score at weeks 1, 2, 4, 8, 12, and 16 • proportions of patients achieving pasi 75 response, ≥90% reduction from baseline in pasi (pasi 90) response, spga 0/1, and dlqi 0/1 responses at these time points were also evaluated • the analyses primarily focused on the onset of action of deucravacitinib vs placebo to help contextualize the outcomes to be expected in clinical practice results baseline patient demographics and disease characteristics • baseline patient demographics and disease characteristics, including pasi, pssd symptom score, dlqi, bsa, and spga×bsa, were similar across treatment groups in both trials and representative of a population with moderate to severe plaque psoriasis (table 1) table 1. baseline patient demographics and disease characteristics poetyk pso-1 poetyk pso-2 placebo (n=166) deucravacitinib (n=332) placebo (n=255) deucravacitinib (n=511) age, y, mean (sd) 47.9 (14.0) 45.9 (13.7) 47.3 (13.6) 46.9 (13.4) weight, kg, mean (sd) 89.1 (22.3) 87.9 (21.8) 91.5 (20.2) 92.3 (21.9) female, n (%) 53 (31.9) 102 (30.7) 74 (29.0) 175 (34.2) race, n (%) white 128 (77.1) 267 (80.4) 232 (91.0) 474 (92.8) asian 34 (20.5) 59 (17.8) 8 (3.1) 24 (4.7) other 4 (2.4) 6 (1.8) 15 (5.9) 13 (2.6) disease duration, y, mean (sd) 17.3 (12.8) 17.1 (12.4) 19.9 (12.8) 19.6 (12.9) prior systemic treatment use, n (%) biologic 63 (38.0) 130 (39.2) 83 (32.5) 165 (32.3) no prior systemic therapy 57 (34.3) 132 (39.8) 116 (45.5) 237 (46.4) spga, n (%) 3 = moderate 128 (77.1) 257 (77.4) 217 (85.1) 408 (79.8) 4 = severe 37 (22.3) 75 (22.6) 38 (14.9) 103 (20.2) pasi, mean (sd) 20.7 (8.0) 21.8 (8.6) 21.1 (9.0) 20.7 (7.5) bsa, %, mean (sd) 25.3 (16.9) 26.6 (15.9) 25.3 (15.7) 26.3 (15.8) spgaxbsa, mean (sd) 82.1 (57.3) 86.9 (56.1) 81.1 (56.3) 85.0 (54.6) pssd symptom score,a mean (sd) 51.4 (26.8) 51.7 (25.2) 50.1 (24.8) 52.3 (26.3) dlqi, mean (sd) 11.4 (6.6) 12.0 (6.7) 11.8 (6.8) 11.8 (6.5) apssd symptom score is the average severity of 5 symptoms (itch, pain, burning, stinging, and skin tightness) over the previous 24 h scored on a scale ranging from 0 (absent) to 100 (worst). bsa, body surface area; dlqi, dermatology life quality index; pasi, psoriasis area and severity index; pssd, psoriasis symptoms and signs diary; spga, static physician’s global assessment. efficacy • deucravacitinib treatment was associated with significantly larger mean changes from baseline in pasi vs placebo as early as week 1 in both trials (p<0.0001; figure 3) • significantly larger mean percentage changes from baseline in pasi were seen in the deucravacitinib group vs the placebo group as early as week 1 in both trials (p<0.001; figure 4) — approximately 40% improvement was seen by week 4 in the deucravacitinib group in both trials figure 3. improvements in mean pasi score over 16 weeks poetyk pso-1 poetyk pso-2 placebo (n=166) deucravacitinib (n=332) placebo (n=255) deucravacitinib (n=511) baseline pasi, mean (sd) 20.7 (8.0) 21.8 (8.6) 21.1 (9.0) 20.7 (7.5) deucravacitinib 6 mg qdplacebo -16 -14 -12 -10 -8 -6 -4 -2 0 0 4 8 12 16 weeks -16 -14 -12 -10 -8 -6 -4 -2 0 0 4 8 12 16 weeks 4.4 14.0* * * * * * 4.2 14.1* * * * * * 1 2 1 2 a d ju st e d m e an ( se ) ch an ge f ro m b as e li n e p a si a d j u st e d m e an ( se ) ch an ge f ro m b as e li n e p a si poetyk pso-1 poetyk pso-2 *p<0.0001 vs placebo. modified baseline observation carried forward was used to impute missing data. pasi, psoriasis area and severity index; qd, once daily. figure 4. percentage improvements in mean pasi score over 16 weeks poetyk pso-1 poetyk pso-2 placebo (n=166) deucravacitinib (n=332) placebo (n=255) deucravacitinib (n=511) baseline pasi, mean (sd) 20.7 (8.0) 21.8 (8.6) 21.1 (9.0) 20.7 (7.5) deucravacitinib 6 mg qdplacebo a d ju st e d m e an ( se ) % c h an ge fr o m b as e li n e p a si a d ju st e d m e an ( se ) % c h an ge fr o m b as e li n e p a si -80 -60 -40 -20 0 0 4 8 12 16 -80 -60 -40 -20 0 0 4 8 12 16 19.5% 66.5%† † * † † † 21.0% 68.1%† † † † † † 1 2 1 2 25.7% 42.8% 25.9% 39.6% weeksweeks poetyk pso-1 poetyk pso-2 *p<0.001 vs placebo. †p<0.0001 vs placebo. modified baseline observation carried forward was used to impute missing data. pasi, psoriasis area and severity index; qd, once daily. • significantly larger mean changes from baseline in bsa percentage involvement were observed in the deucravacitinib group vs the placebo group by week 2 (p<0.01; figure 5) • treatment with deucravacitinib resulted in significantly larger mean changes from baseline vs placebo in spga×bsa by week 1 in both trials (p<0.01; figure 6) figure 5. improvements in bsa involvement over 16 weeks poetyk pso-1 poetyk pso-2 placebo (n=166) deucravacitinib (n=332) placebo (n=255) deucravacitinib (n=511) baseline bsa, %, mean (sd) 25.3 (16.9) 26.6 (15.9) 25.3 (15.7) 26.3 (15.8) deucravacitinib 6 mg qdplacebo -18 -16 -14 -12 -10 -8 -6 -4 -2 0 0 4 8 12 16 -18 -16 -14 -12 -10 -8 -6 -4 -2 0 0 4 8 12 16 2.5 14.9 * † † † 3.1 16.6 † † * † a d ju st e d m e an ( se ) ch an ge fr om b as e li n e % b sa a d ju st e d m e an ( se ) ch an ge fr om b as e li n e % b sa 1 2 1 2 weeksweeks poetyk pso-1 poetyk pso-2 *p<0.01 vs placebo. †p<0.0001 vs placebo. modified baseline observation carried forward was used to impute missing data. bsa, body surface area; qd, once daily. figure 6. improvements in spga×bsa over 16 weeks 1 2 1 2 -80 -60 -40 -20 0 0 4 8 12 16 -80 -60 -40 -20 0 0 4 8 12 16 59.5 16.6 59.2 14.4 * † † † † * † † † † a d ju st e d m e an ( se ) ch an ge fr o m b as e li n e s p g a b sa a d ju st e d m e an ( se ) ch an ge fr o m b as e li n e s p g a b sa deucravacitinib 6 mg qdplacebo poetyk pso-1 poetyk pso-2 placebo (n=166) deucravacitinib (n=332) placebo (n=255) deucravacitinib (n=511) baseline spga bsa, mean (sd) 82.1 (57.3) 86.9 (56.1) 81.1 (56.3) 85.0 (54.6) weeksweeks poetyk pso-1 poetyk pso-2 *p<0.01 vs placebo. †p<0.0001 vs placebo. modified baseline observation carried forward was used to impute missing data. bsa, body surface area; qd, once daily; spga, static physician’s global assessment. • deucravacitinib-treated individuals experienced significantly larger mean changes from baseline in pssd symptom score vs placebo by week 2 in pso-1 and as early as week 1 in pso-2 (p<0.01 for both; figure 7) figure 7. improvements in pssd symptom score over 16 weeks 15 deucravacitinib 6 mg qdplacebo poetyk pso-1 poetyk pso-2 placebo (n=166) deucravacitinib (n=332) placebo (n=255) deucravacitinib (n=511) baseline pssd, mean (sd) 51.4 (26.8) 51.7 (25.2) 50.1 (24.8) 52.3 (26.3) -30 -20 -10 0 0 4 8 12 16 * † † † † -30 -20 -10 0 0 4 8 12 16 * 1 2 1 2 a d ju st e d m e an ( se ) ch an ge fr o m b as e li n e p ss d a d ju st e d m e an ( se ) ch an ge fr o m b as e li n e p ss d 3.6 26.7 28.3 † † † 4.7 weeks 8 weeks poetyk pso-1 poetyk pso-2 *p<0.01 vs placebo. †p<0.0001 vs placebo. modified baseline observation carried forward was used to impute missing data. pssd, psoriasis symptoms and signs diary; qd, once daily. • significantly larger mean changes from baseline in dlqi were seen with the deucravacitinib group vs the placebo group by week 1 (p<0.05) in both trials (figure 8) figure 8. improvements in dlqi score over 16 weeks deucravacitinib 6 mg qdplacebo poetyk pso-1 poetyk pso-2 placebo (n=166) deucravacitinib (n=332) placebo (n=255) deucravacitinib (n=511) baseline dlqi, mean (sd) 11.4 (6.6) 12.0 (6.7) 11.8 (6.8) 11.8 (6.5) 1 2 1 2 -10 -8 -6 -4 -2 0 0 4 8 12 16 -10 -8 -6 -4 -2 0 0 4 8 12 16 3.0 7.6 † * † † † 3.3 8.5 * † † † † a d ju st e d m e an ( se ) ch an ge fr o m b as e li n e d lq i a d ju st e d m e an ( se ) ch an ge fr o m b as e li n e d lq i weeksweeks poetyk pso-1 poetyk pso-2 *p<0.05 vs placebo. †p<0.0001 vs placebo. modified baseline observation carried forward was used to impute missing data. dlqi, dermatology life quality index; qd, once daily. • in both trials, significantly higher proportions of patients achieved pasi 75 responses in the deucravacitinib group vs the placebo group by week 4 (p<0.001; figure 9) figure 9. achievement of pasi 75 response over 16 weeks deucravacitinib 6 mg qdplacebo 0 20 40 60 80 100 0 4 8 12 16 58.4%† 12.7% 0 20 40 60 80 100 0 4 8 12 16 † † 53.0%† 9.4% 21 poetyk pso-1 poetyk pso-2 weeks weeks p a si 7 5 r e sp o n se r at e ( 9 5 % c i) , % p a si 7 5 r e sp o n se r at e ( 9 5 % c i) , % 1 2 * † † * *p<0.001 vs placebo. †p<0.0001 vs placebo. modified baseline observation carried forward was used to impute missing data. pasi 75, ≥75% reduction from baseline in psoriasis area and severity index; qd, once daily. • the proportion of patients achieving spga 0/1 response was significantly higher in the deucravacitinib group vs the placebo group by week 4 in pso-1 (p<0.0001) and by week 2 in pso-2 (p<0.001; figure 10) figure 10. achievement of spga 0/1 responsea over 16 weeks poetyk pso-1 poetyk pso-2 deucravacitinib 6 mg qdplacebo 0 20 40 60 80 100 0 4 8 12 16 0 20 40 60 80 100 0 4 8 12 16 † † † sp g a 0 /1 r e sp o n se r at e ( 9 5 % c i) , % 53.6%† 7.2% 49.5%† 8.6% weeks weeks * † † † 1 2 21 sp g a 0 /1 r e sp o n se r at e ( 9 5 % c i) , % aresponse defined as spga score of 0 or 1 with ≥2-point improvement from baseline. *p<0.001 vs placebo. †p<0.0001 vs placebo. nonresponder imputation was used to impute missing data. spga 0/1, static physician’s global assessment score of 0 or 1; qd, once daily. • pasi 90 response rates were significantly higher in the deucravacitinib group vs the placebo group by week 8 in pso-1 (p<0.0001) and week 4 in pso-2 (p<0.05; figure 11) figure 11. achievement of pasi 90 response over 16 weeks poetyk pso-1 poetyk pso-2 deucravacitinib 6 mg qdplacebo 0 20 40 60 80 100 0 4 8 12 16 35.5%† 4.2% 0 20 40 60 80 100 0 4 8 12 16 † † 27.0%† 2.7% weeks weeks p a si 9 0 r e sp o n se r at e ( 9 5 % c i) , % p a si 9 0 r e sp o n se r at e ( 9 5 % c i) , % † † * 1 2 21 *p<0.05 vs placebo. †p<0.0001 vs placebo. nonresponder imputation was used to impute missing data. pasi 90, ≥90% reduction from baseline in psoriasis area and severity index; qd, once daily. • the proportion of patients achieving dlqi 0/1 response was significantly higher in the deucravacitinib group vs the placebo group by week 2 in pso-1 and by week 4 in pso-2 (figure 12) figure 12. dlqi 0/1 responsea through 16 weeks poetyk pso-1 poetyk pso-2 deucravacitinib 6 mg qdplacebo 0 20 40 60 80 100 0 4 8 12 161 2 41.0%† 10.6% 0 20 40 60 80 100 0 4 8 12 161 2 37.6%† 9.8% d lq i 0 /1 r e sp o n se r at e ( 9 5 % c i) , % d lq i 0 /1 r e sp o n se r at e ( 9 5 % c i) , % weeks weeks * * † † * † † aamong patients with baseline dlqi score ≥2. *p<0.05 vs placebo. †p<0.0001 vs placebo. nonresponder imputation was used to impute missing data. dlqi 0/1, dermatology life quality index score of 0 or 1; qd, once daily. • in both trials, the superiority of deucravacitinib vs apremilast was observed as early as week 4 for change from baseline in pasi (figure 13) and all other endpoints assessed (data not shown) figure 13. improvements from baseline pasi score over 16 weeks poetyk pso-1 poetyk pso-2 placebo (n=166) deucravacitinib (n=332) apremilast (n=168) placebo (n=255) deucravacitinib (n=511) apremilast (n=168) baseline pasi score, mean (sd) 20.7 (8.0) 21.8 (8.6) 21.4 (9.0) 21.1 (9.0) 20.7 (7.5) 21.6 (8.4) deucravacitinib 6 mg qdplacebo apremilast 30 mg bid -18 -16 -14 -12 -10 -8 -6 -4 -2 0 0 4 8 12 16 weeks -18 -16 -14 -12 -10 -8 -6 -4 -2 0 0 4 8 12 16 weeks 4.4 14.0*† † † † 4.2 14.1*† † † *† 9.6 10.8 poetyk pso-1 poetyk pso-2 1 2 1 2 *† *† *† *†a d ju st e d m e an c h an ge fr om b as e li n e p a si s co re a d ju st e d m e an c h an ge fr om b as e li n e p a si s co re *p≤0.0019 vs apremilast. †p<0.0001 vs placebo. modified baseline observation carried forward was used to impute missing data. bid, twice daily; pasi, psoriasis area and severity index; qd, once daily. conclusions • in the phase 3 poetyk pso-1 and pso-2 trials, oral deucravacitinib had a rapid onset of action and improved objective and patient-reported efficacy outcomes compared with placebo as early as week 1 • these findings suggest that deucravacitinib treatment provides rapid relief of signs and symptoms in patients with moderate to severe plaque psoriasis • taken together with the primary results from the phase 3 poetyk trials, deucravacitinib, a once-daily, oral, selective tyk2 inhibitor, has the potential to become a valuable treatment of choice and new standard of care for patients with moderate to severe plaque psoriasis references 1. burke jr et al. sci transl med 2019;11:1-16. 2. wrobleski st et al. j med chem 2019;62:8973-8995. 3. papp k et al. n engl j med 2018;379:1313-1321. 4. mease pj et al. presented at the annual scientific meeting of the american college of rheumatology; november 5-9, 2020. acknowledgments • these clinical trials were sponsored by bristol myers squibb. professional medical writing and editorial assistance were provided by peloton advantage, llc, an open health company, parsippany, nj, usa, and were funded by bristol myers squibb. relationships and activities • njk: advisory board, consulting fees: abbvie, boehringer ingelheim, bristol myers squibb, celgene, eli lilly, janssen, leo pharma, novartis, principia, regeneron, sanofi genzyme, sun pharma, and ucb; grant support/principal investigator: abbvie, amgen, argenx, bristol myers squibb, celgene, chemocentryx, eli lilly, galderma, kyowa hakko kirin, leo pharma, menlo, principia, prothena, rhizen, syntimmune, trevi, and xbiotech; speaker: abbvie, eli lilly, janssen, novartis, regeneron, and sanofi genzyme • kp: speakers bureau: abbvie, amgen, astellas, celgene, eli lilly, galderma, janssen, kyowa hakko kirin, leo pharma, merck sharp & dohme, novartis, pfizer, and valeant; grant/research support: abbvie, akros, allergan, amgen, anacor, arcutis, astrazeneca, baxalta, boehringer ingelheim, bristol myers squibb, celgene, coherus, dermira, dow pharma, eli lilly, galderma, genentech, glaxosmithkline, janssen, kyowa hakko kirin, leo pharma, medimmune, meiji seika pharma, merck serono, novartis, pfizer, regeneron, roche, sanofi genzyme, takeda, ucb, and valeant; consultant: abbvie, akros, amgen, arcutis, astellas, astrazeneca, baxalta, baxter, boehringer ingelheim, bristol myers squibb, canfite, celgene, coherus, dermira, dow pharma, eli lilly, forward pharma, galderma, genentech, janssen, kyowa hakko kirin, leo pharma, meiji seika pharma, merck serono, merck sharp & dohme, mitsubishi pharma, novartis, pfizer, regeneron, roche, sanofi genzyme, takeda, ucb, and valeant; honoraria: abbvie, akros, amgen, baxter, boehringer ingelheim, celgene, coherus, eli lilly, forward pharma, galderma, glaxosmithkline, janssen, kyowa hakko kirin, merck serono, merck sharp & dohme, novartis, pfizer, takeda, ucb, and valeant; scientific officer/steering committee/advisory board: abbvie, akros, amgen, anacor, astellas, baxter, boehringer ingelheim, bristol myers squibb, celgene, dow pharma, eli lilly, galderma, janssen, kyowa hakko kirin, merck serono, merck sharp & dohme, novartis, pfizer, regeneron, sanofi genzyme, and valeant • jb: research funds payable to the psoriasis treatment center of new jersey: abbvie, amgen, arcutis, boehringer ingelheim, bristol myers squibb, celgene, corevitas’ psoriasis registry, dermavant, dermira/ucb, eli lilly, glenmark, janssen biotech, kadmon, leo pharma, lycera, menlo, novartis, pfizer, regeneron, sun pharma, taro, and valeant; consultant: abbvie, amgen, celgene, eli lilly, janssen biotech, novartis, sun pharma, and valeant; speaker: abbvie, celgene, eli lilly, janssen biotech, and novartis • pf: grant support: abbvie, amgen, celgene, janssen, leo pharma, lilly, merck, novartis, pfizer, sanofi, and sun pharma; investigator: abbvie, amgen, arcutis, aslan, astrazeneca, boehringer ingelheim, botanix, bristol myers squibb, celgene, celtaxsys, csl, cutanea, dermira, galderma, genentech, glaxosmithkline, hexima, janssen, leo pharma, lilly, merck, novartis, pfizer, regeneron, reistone, roche, sanofi, sun pharma, ucb, and valeant; advisory board: abbvie, amgen, boehringer ingelheim, bristol myers squibb, celgene, galderma, glaxosmithkline, janssen, leo pharma, lilly, merck, novartis, pfizer, sanofi, sun pharma, ucb, and valeant; consultant: bristol myers squibb, galderma, janssen, leo pharma, lilly, novartis, pfizer, roche, and ucb; travel grants: abbvie, galderma, janssen, leo pharma, lilly, merck, novartis, pfizer, roche, sun pharma, and sanofi; speaker for or honoraria from: abbvie, amgen, celgene, galderma, glaxosmithkline, janssen, leo pharma, lilly, merck, novartis, pfizer, roche, and valeant • am: grant/research support, consultant, speakers bureau: abbvie, boehringer ingelheim, bristol myers squibb, celgene, eisai, eli lilly, janssen, kyowa hakko kirin, leo pharma, maruho, mitsubishi tanabe, nichi-iko, nippon kayaku, novartis, pfizer, sun pharma, taiho pharmaceutical, torii pharmaceutical, ucb, and ushio • sb, ec, tw, and jt: employees and shareholders: bristol myers squibb • dt: research support/principal investigator (clinical trials): abbvie, almirall, amgen, biogen idec, boehringer ingelheim, celgene, dermira, ds pharma, eli lilly, galapagos, galderma, janssen-cilag, leo pharma, novartis, pfizer, regeneron, roche, sandoz-hexal, sanofi, and ucb; consultant: abbvie, almirall, amgen, janssen, leo pharma, novartis, roche-posay, sandozhexal, sanofi, and ucb; scientific advisory board: abbvie, amgen, eli lilly, galapagos, janssen-cilag, leo pharma, morphosis, merck sharp & dohme, novartis, pfizer, sanofi, and ucb presented at the fall clinical dermatology conference®; october 21—24, 2021; las vegas, nv, and virtual this is an encore of the 2021 eadv 30th congress poster and the 2021 npf research symposium poster this poster may not be reproduced without written permission from the authors.email for neil j korman, md, phd: neil.korman@uhhospitals.org powerpoint presentation 38 31 36 25 29 23 18 20 22 10 9 13 4 5 2 5 6 3 0 20 40 60 80 100 120 ≤3 palms n = 2,497 4-10 palms n = 612 >10 palms n = 91 pa tie nt s (% ) topical + oral + biologic oral + biologic biologic ± topical oral ± topical topical only no medication uplift more than half of uplift patients with limited bsa (≤3 palms) perceived their pso as moderate or severe mark lebwohl1; richard g. langley2; carle paul3; lluis puig4; kristian reich5; peter van der kerkhof6; lihua tang7; sven richter7; benoit guerette7; paolo gisondi8 1icahn school of medicine at mount sinai, new york, ny, usa; 2division of dermatology, department of medicine, dalhousie university, halifax, canada; 3paul sabatier university, toulouse, france; 4hospital de la santa creu i sant pau, barcelona, spain; 5center for translational research in inflammatory skin diseases, institute for health services research in dermatology and nursing, university medical center hamburg-eppendorf, hamburg, germany; 6department of dermatology, radboud university medical center, nijmegan, netherlands; 7amgen inc., thousand oaks, ca, usa; 8university hospital of verona, verona, italy • uplift: quantitative online survey from march 2, 2020, to june 3, 2020 – 4,729 participants (473 dermatologists, 450 rheumatologists, 3,806 patients) • mapp: telephone survey from june 2012 to august 20121,2,6 – 4,207 participants (391 dermatologists, 390 rheumatologists, 3,426 patients)1,2 • the multinational assessment of psoriasis and psoriatic arthritis (mapp) survey provided valuable data on quality of life and unmet needs in patients with psoriasis (pso) and/or psoriatic arthritis (psa)1,2 • since the 2012 mapp survey, pso treatment options have increased1,3-5 • the understanding psoriatic disease leveraging insights for treatment (uplift) survey was designed to better understand how perspectives on treatment-related outcomes have evolved since the mapp survey, particularly for patients with mild to moderate disease. we present patient-reported data from uplift and mapp • more than half of patients in the uplift survey perceived their current pso symptoms as moderate or severe despite limited skin involvement. additionally, many patients were not receiving any medication, suggesting that there remains significant unmet need evolution of patient perceptions of psoriatic disease: results from the understanding psoriatic disease leveraging insights for treatment (uplift) survey • more than half of patients with limited skin involvement reported their current disease as moderate or severe, had pso involvement in special areas, and were receiving topicals or no treatment, suggesting a persistent unmet need in this patient population • in mapp vs. uplift, the proportion of patients describing their disease as moderate to severe on systematic treatment remained relatively low despite the higher number of available treatment options • further research is needed to better understand why a significant proportion of patients with limited skin involvement and pso in special areas perceive their current disease as moderate or severe but do not receive systemic treatment ml: mount sinai – employment; abbvie, amgen inc., arcutis, boehringer ingelheim, dermavant, eli lilly, incyte, janssen, leo pharma, ortho dermatologics, pfizer, and ucb – research funds; aditum bio, allergan, almirall, arcutis, avotres therapeutics, birchbiomed, bmd skincare, boehringer-ingelheim, bristol-myers squibb, cara therapeutics, castle biosciences, corrona, dermavant sciences, evelo, facilitate international dermatologic education, foundation for research and education in dermatology, inozyme pharma, kyowa kirin, leo pharma, meiji seika pharma, menlo, mitsubishi, neuroderm, pfizer, promius/dr. reddy’s laboratories, serono, theravance, and verrica – consultant. rgl: abbvie, amgen inc., boehringer ingelheim, janssen, leo pharma, lilly, novartis, pfizer, and ucb – principal investigator, scientific advisory board, or speaker. cp: no conflicts to disclose. lp: abbvie, amgen inc., boehringer ingelheim, janssen, leo pharma, lilly, novartis, pfizer, regeneron, roche, sanofi, and ucb – fees; abbvie, almirall, amgen inc., baxalta, biogen, boehringer ingelheim, celgene, gebro, janssen, leo pharma, lilly, merck-serono, msd, mylan, novartis, pfizer, regeneron, roche, sandoz, sanofi, and ucb – honoraria and consultant fees; celgene, janssen, lilly, msd, novartis, and pfizer – company-sponsored speakers bureaus. kr: abbvie, affibody, almirall, amgen inc., avillion, biogen, boehringer ingelheim, bristol-myers squibb, celgene, centocor, covagen, dermira, forward pharma, fresenius medical care, galapagos, glaxosmithkline, janssen-cilag, kyowa kirin, leo, lilly, medac, merck sharp & dohme, novartis, miltenyi biotec, ocean pharma, pfizer, regeneron, samsung bioepis, sanofi, sun pharma, takeda, ucb, valeant, and xenoport – paid speaker and/or participated in clinical trials. pvdk: abbvie, almirall, bristol-myers squibb, celgene, dermavant, eli lilly, janssen, leo pharma, and novartis – consultant and/or lecturer. lt, sr, & bg: amgen inc. – employment. pg: abbvie, amgen inc., janssen, leo pharma, lilly, novartis, pfizer, sanofi, and ucb – consultant and grant/research support. funding statement: this survey was funded by amgen inc. writing support was funded by amgen and provided by amy shaberman, phd, of peloton advantage, llc, an open health company. 1. lebwohl mg, et al. j am acad dermatol. 2014;70:871-881. 2. van de kerkhof pc, et al. j eur acad dermatol venereol. 2015;29:2002-2010. 3. otezla [package insert]. thousand oaks, ca: amgen, inc; 2020. 4. ilumya [package insert]. whitehouse station, nj: merck & co inc; 2018. 5. tremfya [package insert]. horsham, pa: janssen biotech, inc; 2017. 6. lebwohl mg, et al. am j clin dermatol. 2016;17:87-97. © 2021 amgen inc.presented at: the 2021 winter clinical dermatology conference–hawaii® uplift n = 3,806 mapp n = 3,426 age, years, mean 45.1 54.8 female, n (%) 1,892 (49.7) 2,026 (59.1) comorbidities, n (%) arthritis* 1,157 (30.4) 1,179 (34.4) cancer 693 (18.2) 189 (5.5) depression 1,257 (33.0) 626 (18.3) diabetes 903 (23.7) 489 (14.3) heart disease 520 (13.7) 345 (10.1) hypertension 1,342 (35.3) 1,121 (32.7) inflammatory bowel disease† 512 (13.5) 129 (3.8) liver disease 419 (11.0) 71 (2.1) n represents the total sample. the number of patients with data available may vary. *osteoarthritis or rheumatoid arthritis in uplift and any arthritis in mapp. †crohn’s disease and ulcerative colitis. results patients in uplift had higher rates of certain comorbidities but lower mean age vs. patients in mapp • both studies included adult patients (≥18 years of age) who reported that they had been diagnosed with pso and/or psa by a healthcare practitioner conclusion synopsis methods disclosures & funding statement in uplift, 60% of pso patients with limited bsa and involvement in ≥1 special area reported their current disease as moderate or severe of these, 51% were receiving topicals or no treatment body surface area in both surveys, high proportions of patients reported that they were not currently receiving treatment • in uplift, 58% of patients with limited bsa rated their current pso symptoms as moderate or severe • many had pso involvement in special areas (scalp, face, palms and/or soles, nails, genitals) and were not receiving treatment countries united states canada united kingdom france germany italy spain japan uplift patients mapp1 patients n = 1,005 400 400 415 406 400 400 1,006 403 400 404 403 401 398 391n = results face: 28% scalp: 54% palms: 17% nails: 17% genitals: 12% soles†: 13% uplift n = 3,606 mapp n = 2,416 face: 15% scalp: 48% palms: 12% nails: 11% genitals: 7% soles†: 11% *among patients with pso and presence of skin symptoms. †soles of feet in uplift; soles in mapp. note: a patient may have more than one special area. in both uplift and mapp: • most patients had pso • similar proportions of patients reported having limited skin involvement (body surface area [bsa] ≤3 palms) 67% 5% 28% pso only psa only pso + psa 79% 7% 14% pso only psa only pso + psa uplift n = 3,806 mapp n = 3,426 diagnosis self-reported pso severity 0 20 40 60 80 100 uplift n = 3,200 mapp n = 2,549 pa tie nt s, % bsa >10 palms bsa 4-10 palms bsa ≤3 palms 3 19 6 15 pso in special areas was commonly reported in both surveys.* in uplift, >50% of patients had scalp involvement 41 32 37 53 55 52 4 8 5 2 4 5 1 1 1 0 20 40 60 80 100 120 ≤3 palms n = 2,122 4-10 palms n = 393 >10 palms n = 166 pa tie nt s (% ) oral + biologic biologic ± topical oral ± topical topical only no medication mapp body surface area 78 79 objective • the understanding psoriatic disease leveraging insights for treatment (uplift) survey was designed to better understand how perspectives on treatment-related outcomes have evolved since the mapp survey, particularly for patients with mild to moderate disease. we present patient-reported data from uplift and mapp slide number 1 skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 399 resident competition research articles cutaneous metastasis from gastric carcinoma, an uncommon clinical presentation fabrizio galimberti, md, phd,1 gregory perez, md1,2 1dr. philip frost department of dermatology and cutaneous surgery, university of miami miller school of medicine, miami, fl 2miami veterans affairs healthcare system, miami, fl a 43-year-old well appearing japaneseamerican female was referred by a local medical oncologist for evaluation of a new onset truncal lesion. she reported a past medical history of a previous malignancy that was now in remission. no additional details were available. clinical examination revealed an isolated mobile pink plaque on the upper back (figure 1). the lesion measured 19mm and was asymptomatic, well circumscribed, with no secondary changes. a punch biopsy was obtained which showed malignant cells infiltrating collagen bundles. the infiltrating cells were arranged both individually and in an “indian file” like pattern (figure 2). at higher magnification, typical signet ring cells with eccentrically located hyperchrormatic nuclei were observed. infiltrating cells stained positive for cam5.2 and negative for estrogen receptor. a diagnosis of metastatic gastric carcinoma (mgc) was established and wide resection of the lesion with clear margins was obtained. unfortunately, she succumbed to her disease within one year of this diagnosis. figure 1. asymptomatic lesions on the back. abstract cutaneous metastases are a late event associated with poor prognosis. here we report a case of gastric carcinoma associated cutaneous metastasis in a patient who reported a history of an unspecified malignancy under remission. this case report serves to highlight cutaneous metastases as a rare late complications of malignancies, including those that may have been previously considered in remission, associated with poor prognosis. case report skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 400 figure 2. hematoxylin and eosinophil staining with infiltrating cells arranged individually and in an “indian file” like pattern. in general, cutaneous metastases often present at a late disease stage and are associated with diffuse metastatic disease and poor prognosis. cutaneous metastases occur in 0.6 to 10.4% of cancer patients.1 the most common sources of skin metastases in women are breast, colon cancer, and melanoma whereas the leading causes in men are melanoma, lung, and colon cancer.2,3 even more rarely, cutaneous metastases are the initial presentation of occult internal malignancy, occurring in only 0.8% of patients.4 in these cases, the most likely primary malignancies are lung, kidney, and ovaries.4 the mechanisms that predispose certain malignancies to metastasize to skin are unclear. gastric cancer (gc) accounts for 6% of all skin metastases in males and only 1% in females.5 although incidence rates have been declining, gc is the fifth most common malignancy in the world with about 1 million new cases diagnosed annually and the third most common cause of cancer related death worldwide. the incidence of gc is highly dependent on ethnicity, diet, and infection history, in particular by h. pylori and hpv. incidence is tenfold higher in asia, eastern europe and parts of central and south american countries than in western countries, possibly linked to the prevalence of h. pylori in those regions. also, incidence is twofold higher in men than women.4,6 different risk factors are linked to gc of different areas of the stomach: distal and antral cancers are associated with h. pylori, alcohol, and low fruit/high consumption of process meats, which are common in east asia, whereas proximal cancers (cardia) are linked to obesity and tumors of the gastroesophageal junction with barrett's esophagus, which is more common in nonasian countries.4,6 the survival rate for gc is among the lowest of all solid malignancies: 5year survival rate of about 30% for gc and 3.1% for advanced gc. analysis of the us nci's surveillance, epidemiology, and end results (seer) showed median overall survival of 6 months in patients younger than 44 years of age and of 3 months in patients older than 75.4,6 management of mgc is challenging. patients with locally advanced or mgc should be started on systemic treatments as these have been shown to increase survival and quality of life as compared to supportive care alone.7 combinations of platinum and fluoropyrimidines with or without anthracycline or taxanes are the preferred treatments.4,6,7 molecular targeting is also being investigated. in particular, trastuzumab has shown promising results in treatment of her-2 positive mgc. (7) the role of surgery in mgc is controversial. in specific, the regatta study showed no survival advantage with palliative gastrectomy plus chemotherapy as compared to chemotherapy alone, suggesting that palliative resection yielded no benefits. however, a subset analysis revealed that discussion skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 401 patients with gc in lower gastric bodies had relatively favorable outcomes, suggesting that surgical intervention may be beneficial for some mgc patients.8 the appearance of new cutaneous lesions on patients with a history of malignancy, even remote, should be thoroughly investigated to rule out cutaneous metastases. this case report heightens the awareness of this rare presentation associated with poor prognosis. conflict of interest disclosures: none funding: none corresponding author: fabrizio galimberti, md, phd dr. philip frost department of dermatology and cutaneous surgery, university of miami miller school of medicine miami, fl 33125 email: fbrzgalimberti@gmail.com references: 1. alcaraz i, cerroni l, rütten a, kutzner h, requena l. cutaneous metastases from internal malignancies: a clinicopathologic and immunohistochemical review. am. j. dermatopathol. 2012;34(4):347–93 2. sittart ja de s, senise m. cutaneous metastasis from internal carcinomas: a review of 45 years. an. bras. dermatol. 2013;88(4):541–4 3. wong cyb, helm ma, kalb re, helm tn, zeitouni nc. the presentation, pathology, and current management strategies of cutaneous metastasis. north am. j. med. sci. 2013;5(9):499–504 4. lookingbill dp, spangler n, sexton fm. skin involvement as the presenting sign of internal carcinoma. a retrospective study of 7316 cancer patients. j. am. acad. dermatol. 1990;22(1):19– 26 5. sitarz r, skierucha m, mielko j, offerhaus gja, maciejewski r, polkowski wp. gastric cancer: epidemiology, prevention, classification, and treatment. cancer manag. res. 2018;10:239–48 6. karimi p, islami f, anandasabapathy s, freedman nd, kamangar f. gastric cancer: descriptive epidemiology, risk factors, screening, and prevention. cancer epidemiol. biomark. prev. publ. am. assoc. cancer res. cosponsored am. soc. prev. oncol. 2014;23(5):700–13 7. gunturu ks, woo y, beaubier n, remotti he, saif mw. gastric cancer and trastuzumab: first biologic therapy in gastric cancer. ther. adv. med. oncol. 2013;5(2):143–51 8. fujitani k, yang h-k, mizusawa j, kim y-w, terashima m, han s-u, et al. gastrectomy plus chemotherapy versus chemotherapy alone for advanced gastric cancer with a single non-curable factor (regatta): a phase 3, randomised controlled trial. lancet oncol. 2016;17(3):309–18 conclusion mailto:fbrzgalimberti@gmail.com fall clinical 2018 idp-121 hispanic and tolerability novel tretinoin 0.05% lotion for the once-daily treatment of moderate-to-severe acne vulgaris in a hispanic population fran e cook-bolden, md1, susan h weinkle2, md, eric guenin, pharmd, phd3, varsha bhatt, phd4 1skin specialty dermatology and department of dermatology, mount sinai hospital center, new york, ny; 2 dermatology, university of south florida, tampa, fl; 3ortho dermatologics, bridgewater, nj; 4dow pharmaceutical sciences inc., petaluma, ca. . presented at the fall clinical dermatology conference, october 18-21, 2018, las vegas, nv background • acne vulgaris (acne) is the most common dermatologic diagnosis seen in a hispanic population • despite their growing demographics in the us, there are few studies evaluating acne treatment in this population • potential for skin irritation and dryness, as well as pigmentary changes are key concerns • a new lotion formulation of tretinoin has recently been developed leveraging polymerized emulsion technology with the aim to improve both efficacy and tolerability. objective • to determine the efficacy and safety of tretinoin 0.05% lotion in treating moderate-tosevere acne in a hispanic population. methods • post hoc analysis of two multicenter, randomized, double-blind, vehiclecontrolled phase 3 studies in moderate or severe acne • hispanic subjects (aged 11 to 50 years, n=766) were randomized (1:1) to receive tretinoin 0.05% lotion or vehicle, oncedaily for 12 weeks • cerave® hydrating cleanser and cerave® moisturising lotion (l’oreal, ny) were provided for optimal moisturization/cleaning of the skin • efficacy assessments included changes in baseline inflammatory and noninflammatory lesions and treatment success (at least 2-grade reduction in evaluator’s global severity score [egss] and clear/almost clear) • safety, adverse events (aes) and cutaneous tolerability were evaluated throughout. supported by ortho dermatologics © 2018 all rights reserved results • at week 12, mean percent reduction in inflammatory and noninflammatory lesion counts were 60.1% and 53.0% respectively compared with 51.1% and 38.7% with vehicle (p£0.001) in the hispanic population, figures 1 and 2 • treatment success was achieved by 19.6% of patients by week 12, compared with 12.7% on vehicle (p=0.015), figure 3 • the majority of aes were mild and transient. there were four serious aes (saes) reported (two each group) • the most frequently reported treatment related aes with tretinoin 0.05% lotion were application site pain (2.0%), dryness (1.4%) and erythema (1.2%), table 1 • local cutaneous safety and tolerability assessments were generally mild-tomoderate at baseline and improved by week 12 • slight increases in mean scores were observed for scaling and burning within the first four weeks and appeared to be transient. conclusion tretinoin 0.05% lotion was significantly more effective than its vehicle in achieving treatment success and reducing inflammatory and noninflammatory acne lesions in a hispanic population. the new lotion formulation was welltolerated, and all treatment-related aes were both mild and transient in nature. figure 1: percent change in inflammatory lesions from baseline to week 12 in hispanic subpopulation (itt population pooled data, ls mean) table 1: treatment-emergent and related adverse event (ae) characteristics through week 12 (pooled data – safety population) hispanics figure 3: evaluator ’s global severity scores. patients with at least a 2-grade improvement and ‘clear ’ or ‘almost clear at each study visit hispanic subpopulation (itt population pooled data) figure 2: percent change in noninflammatory lesions from baseline to week 12 hispanic subpopulation (itt population, ls mean) tretinoin 0.05% lotion (n=345) vehicle lotion (n=379) patients reporting any teae 47 (13.6%) 67 (17.7%) patients reporting any sae 2 (0.6%) 2 (0.5%) patients who died 0 (0.0%) 0 (0.0%) patients who discontinued due to teae 3 (0.9%) 0 (0.0%) severity of aes reported mild 36 (10.4%) 42 (11.1%) moderate 9 (2.6%) 19 (5.0%) severe 2 (0.6%) 6 (1.6%) relationship to study drug related 15 (4.3%) 7 (1.8%) unrelated 32 (9.3%) 60 (15.8%) treatment related aes reported by ≥1% patients application site pain 7 (2.0%) 0 (0.0%) application site dryness 5 (1.4%) 1 (0.3%) application site erythema 4 (1.2%) 0 (0.0%) -30% -47% -60% -28% -40% -51% -70% -60% -50% -40% -30% -20% -10% 0% tretinoin 0.05% lotion (n=371) vehicle (n=395) p e rc e n t ch an g e f ro m b as e lin e in m e an in fl am m at o ry le si o n s baseline week 4 week 8 week 12 *p=0.006 versus vehicle **p=0.001 versus vehicle * ** -26% -40% -53% -20% -29% -39% -60% -50% -40% -30% -20% -10% 0% tretinoin 0.05% lotion (n=371) vehicle (n=395) p e rc e n t ch an g e f ro m b as e lin e in m e an n o n in fl am m at o ry le si o n s baseline week 4 week 8 week 12 ** *** *p=0.006 versus vehicle **p=0.001 versus vehicle ***p<0.001 versus vehicle * 3% 7% 20% 3% 6% 13% 0% 5% 10% 15% 20% 25% 30% week 4 week 8 week 12 tretinoin 0.05% lotion (n=371) vehicle (n=395) t re at m e n t s u cc e ss – p e rc e n t o f p at ie n ts w it h t w o g ra d e o r g re at e r r e d u ct io n in e g s s f ro m b as e lin e a n d ‘c le ar ’ o r ‘a lm o st c le ar ’ *p=0.015 versus vehicle * powerpoint presentation references •lesions on the head and neck in the ≥18 yo population were analyzed from the cohort published in estrada et al.; samples are described in table 1. •clinically diagnosed melanomas tested with the 31-gep (prognostic melanoma test available from castle biosciences inc.) were included in this study. benign samples were acquired from 7 centers. benign samples were reviewed and included in the study if 2/3 or 3/3 diagnoses were concordant. •the 35-gep utilizes dual algorithms based on neural networks to provide a result of benign, intermediate-risk or malignant.7 table 2. performance of the 35-gep in different subtypes of nevi and melanoma​ of the head and neck results table 3. 35-gep accuracy metrics in a subset of lesions located on the head and neck methods synopsis dysplastic nevi had different degrees of atypia: a – mild (n=1); b – mild (n=1), moderate (n=1).​ table 1. demographic information performance of a 35-gene expression profile test in suspicious pigmented lesions of the head and neck clay cockerell, m.d.1, mathew s. goldberg, m.d.2,3, sarah i. estrada, m.d.4, gregory a. hosler, m.d., ph.d.5, howard l. martin, m.d.6, brooke h. russell, ph.d.2, olga zolochevska, ph.d.2, natalie d. depcik-smith, m.d.7, nathan j. cleaver, d.o.8 1cockerell dermatopathology, dallas, tx; 2castle biosciences, inc., friendswood, tx; 3icahn school of medicine at mount sinai, ny; 4affiliated dermatology, scottsdale, az; 5propath, dallas, tx; 6sagis, houston, tx; 7aurora diagnostics gpa laboratories, greensboro, nc; 8cleaver medical group, cumming, ga. •the accurate diagnosis of melanocytic neoplasms is a significant clinical challenge in dermatopathology; while histopathologic assessment is frequently sufficient, high rates of diagnostic discordance are reported.1-4 •visual assessment of hematoxylin and eosin (h&e) stained lesions is inherently subjective and relies on expert interpretation and integration of a wide spectrum of architectural and cytologic features that are weighted differently based on the presumed subtype of melanocytic neoplasm and heavily influenced by the pathologists’ personal experience and training.5 •difficult-to-diagnose lesions are commonly sent for second opinions to expert dermatopathologists who have more experience with challenging cases; however, the nature of many lesions remains ambiguous with discordant rates of diagnoses ranging from 25-43%.1,6 •the 35-gene expression profile (gep) test has reported accuracy metrics of 99.1% sensitivity, 96.2% specificity, 96.1% positive predictive value (ppv) and 99.1% negative predictive value (npv) within the clinically available ≥18-year-old (yo) population (n=474).7 •the 35-gep test is intended to refine diagnoses of melanocytic neoplasms by providing clinicians with an objective ancillary tool with high accuracy. •the test provides a narrow intermediate-risk zone of 2.86% in lesions on the head and neck. •the most common melanoma subtype was lentigo maligna melanoma and the 35-gep performed well in this subtype. the most common benign subtype was intradermal nevus and the 35-gep also performed well in this subtype. •a test with these accuracy metrics has been shown to alleviate uncertainty in difficult-to-diagnose lesions leading to recommendations for decreased unnecessary procedures while appropriately identifying at-risk patients.9 conclusions funding: this study was sponsored by castle biosciences, inc. (cbi), which provided funding to contributing centers for tissue and clinical data retrieval. sie is a cbi advisor and shareholder. cc is a cbi advisor. bhr and oz are employees and shareholders of cbi. msg is an employee of cbi. funding & disclosures 1. elmore et al. bmj. 2017;357:j2813 2. shoo et al. j am acad dermatol. 2010;62(5):751-756 3. patrawala et al. j am acad dermatol. 2016;74(1):75-80 4. farmer et al. hum pathol. 1996;27(6):528-531 samples that received the intermediate-risk result were excluded from the calculation. the ppv and npv were calculated with an assumption that the cohort presented here is a random sample of the population. ppv – positive predictive value; npv – negative predictive value; ci – confidence interval. 35-gep result ​≥18 yo population benign, n​ intermediaterisk, n​ malignant, n​ melanomas​ 1 1 48 desmoplastic​ 0 0 4 lentiginous​ 0 0 2 lentigo maligna​ 0 0 15 in situ​ 0 0 7 nevoid​ 0 0 3 nodular​ 1 0 9 spitzoid​ 0 1 0 superficial spreading​ 0 0 8 nevi​ 53 2 0 blue​ 14 1 0 common nevi​ compound​ 3 0 0 intradermal​ 17 0 0 junctional​ 1 0 0 not specified​ 10 0 0 dysplastic​ compound​ 4a 0 0 junctional​ 2b 0 0 spitz​ 2 1 0 5. gonzalez et al. j am acad dermatol. 2017;77(3):543548 6. piepkorn et al. jama netw open. 2019;2(10):e1912597 7. estrada et al. skin j cutan med. 2020;4(6):506-522 8. kienstra et. al. cancer control. 2005;12(4):242-247 9. farberg et. al. skin j cutan med. 2020;4(6):523-533 melanoma​ benign nevi​ n=50 n=55 age, median (range)​ 73 (31-92)​ 51 (18-90)​ sex, % male​ 84 36 breslow thickness, mm (range)​ 1.1 (0.2-4.0)​ na​ t stage, % (n)​ t0 14 (7) t1a​ 22 (11)​ t1b​ 26 (13)​ t2a​ 12 (6)​ t2b​ 8 (4)​ t3a​ 12 (6)​ t3b​ 4 (2)​ unknown 2 (1) ulceration % (n)​ present​ 14 (7)​ absent​ 70 (35)​ not addressed​ 16 (8) 100 (55)​ sub-location on head/neck, % (n) cheek 24 (12) 24 (13) ear 8 (4) 5.5 (3) forehead 8 (4) 9 (5) lip 0 (0) 4 (2) neck 26 (13) 16 (9) nose 8 (4) 5 (3) scalp 20 (10) 31 (17) other 6 (3) 5.5 (3) n=105 35-gep​ 95% ci​ sensitivity​ 97.96%​ 89-100% specificity​ 100%​ 93-100% ppv​ 100%​ 93-100% npv​ 98.15%​ 90-100% intermediaterisk result​ 2.86%​ melanoma in situ and invasive melanoma of the head and neck require special consideration in regard to excision, surgical staging, and treatment regimens, often making diagnostic timing and accuracy critical for this subset of lesions.8 our objective is to demonstrate accuracy of the 35-gep within lesions located on the head and neck. objective microsoft word september 2020 cc 953 proof.docx skin september 2020 volume 4 issue 5 copyright 2020 the national society for cutaneous medicine 438 covid concepts maskne: exacerbation or eruption of acne during the covid-19 pandemic tamar aliya gomolin bsc1, abigail cline, phd, md2, marian russo, md2 1new york medical college, valhalla, ny 2department of dermatology, metropolitan hospital, new york, ny although covid-19 has decreased dermatology outpatient clinic visits, acne remains the most common condition among patients requesting appointments.1 the hashtag “maskne” is trending on instagram with over 22,000 posts detailing this widespread struggle. the use of masks may be a contributing factor to acne mechanica.1 acne mechanica is unique from acne vulgaris which includes symptoms like burning and/or pruritus.2 additionally, pruritus induces scratching, thereby aggravating acne mechanica and compromising mask protection. stopping mechanical insults is crucial to treating acne mechanica;2 however, covid-19 poses a unique challenge as mask wearing is crucial to limiting exposure. besides mechanical factors, mask wearing exacerbates acne due to sweating and increased humidity, leading to swelling of epidermal keratinocytes of the pilosebaceous follicle and obstruction.3 changes to surface sebum composition and skin hydration may disrupt the skin barrier, leading to changes in skin microflora.3 therefore, “maskne” treatment should center on maintaining skin barrier integrity. dermatologists have proposed the term folliculitis mechanica to describe inflammatory cutaneous lesions caused by mechanical injury on body areas which may not be prone to acne. the lesions do not present a typical clinical and histological acne vulgaris profile.2 while acne mechanica is localized to seborrheic areas, such as the face, back and chest, folliculitis mechanica occurs anywhere a hair follicle has mechanical injury.2 histologically, acne mechanica is identical to acne vulgaris; however, purely hyperkeratotic and abstract although the covid-19 outbreak has decreased dermatology outpatient clinic visits, acne remains the most common condition among patients requesting an appointment. the widespread use of face masks may be a contributing factor to acne mechanica and folliculitis mechanica, where stopping the mechanical insult is essential to treatment. however, covid-19 poses a unique challenge as mask wearing is crucial to limiting viral exposure. although reported cases of mask-associated facial dermatoses are largely documented in healthcare workers, the general population is being affected by “maskne”. pathogenesis and treatment options are discussed and the importance of counseling patients on proper skin hygiene is highlighted. as mask use increases, dermatologists should anticipate this trend in acne flare-ups. skin september 2020 volume 4 issue 5 copyright 2020 the national society for cutaneous medicine 439 polymorphic inflammatory lesions are seen in folliculitis mechanica.2 clinically, acne mechanica may have chronic long-lasting flare-ups; however, flare-ups due to folliculitis mechanica quickly resolve when mechanical forces are removed.2 even acne-free patients are experiencing first-time eruptions. ‘maskne’ described by patients with a first-time eruption may represent folliculitis mechanica or acne mechanica. furthermore, patients with a history of acne may present with folliculitis mechanica. for example, a 26-year-old violinist with a 6-year history of acne developed papulopustular and painful nodulocystic lesions below the right jawline2 and was diagnosed with folliculitis mechanica caused by pressure from the violin.2 proposed treatment guidelines include wearing properly fitted masks, applying noncomedogenic moisturizers to the face before wearing personal protective equipment (ppe) to lubricate the skin and reduce friction, and avoiding washing the face with hot water or irritants like ethanol, which breakdown the skin’s protective barrier. for mask-induced pruritus, placing two to three layers of gauze inside the mask may help.4 as mask use increases, dermatologists may see an increase in maskne cases. although mask-associated facial dermatoses are largely documented in healthcare workers in the literature, the general population is clearly being affected by ‘maskne’. dermatologists should counsel patients regarding proper skin hygiene: to avoid over cleansing, mild cleansers close to skin’s natural ph (ph 5), should be used in combination with non-comedogenic moisturizing creams. exfoliation with alpha or beta hydroxyl acids can be used to decrease hyperkeratosis.2 this skincare regimen should be sufficient for patients with folliculitis mechanica. however, if ‘maskne’ persists despite the above regimen, lesions may represent acne mechanica rather than folliculitis mechanica. conventional acne vulgaris treatments may then be necessary, especially if the condition is associated with severe hyperseborrhoea.2 conflict of interest disclosures: none funding: none corresponding author: tamar aliya gomolin, bsc 40 sunshine cottage rd valhalla, ny 10595 phone: 514-834-0995 email: gomolin.tamar@gmail.com references: 1. kutlu ö, güneş r, coerdt k, metin a, khachemoune a. the effect of the "stay-athome" policy on requests for dermatology outpatient clinic visits after the covid-19 outbreak. dermatol ther. 2020:e13581. 2. dreno b, bettoli v, perez m, bouloc a, ochsendorf f. cutaneous lesions caused by mechanical injury. eur j dermatol. 2015;25(2):114-21. 3. han c, shi j, chen y, zhang z. increased flare of acne caused by long-time mask wearing during covid-19 pandemic among general population [published online ahead of print, 2020 may 29]. dermatol ther. 2020;e13704. doi:10.1111/dth.13704 4. masood s, tabassum s, naveed s, jalil p. covid-19 pandemic & skin care guidelines for health care professionals. pak j med sci. 2020;36(covid19-s4):s115-s7. skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 482 original article characterizing the effect of the covid-19 pandemic on the dermatology literature sydney a. weir, bs1, reagan hattaway, bs1, nikhi p. singh, bs1, carter j. boyd, md, mba2, kshipra hemal, md3 1 university of alabama at birmingham school of medicine, birmingham, al 2 hansjörg wyss department of plastic surgery, nyu langone, new york, ny 3 wake forest school of medicine, winston salem, nc the covid-19 pandemic has undoubtedly changed medical practice across the globe. dermatologists have played an integral role in diagnosing and treating various skin conditions related to covid-19. the dermatology literature has reflected the challenges faced by dermatologists throughout the pandemic.1 given the widespread interest in understanding the pandemic and its effects on the field of dermatology, we conducted an analysis of the dermatology literature to characterize the literature’s content, trends, and the abstract introduction: the covid-19 pandemic has impacted multiple aspects of medicine, including research focus and medical literature. specifically, the dermatology literature has reflected the challenges faced by dermatologists throughout the pandemic1. given the widespread interest in understanding the pandemic and its effects on the field of dermatology, we conducted an analysis of the dermatology literature to characterize the literature’s impact, content, trends, and the publication process. we anticipated that there would be more interest in dermatology publications pertaining to covid-19. methods: journal citation reports was used to select the 15 dermatology journals with the highest impact factor in 2019, and all articles published in these journals in 2020 were evaluated2. altmetric attention score (aas) was recorded for each article. for covid-19 related articles, we also assessed whether aas and citations varied by the type of article (editorial, original article, or guideline) and subspecialty of dermatology to which the article pertained. results: analysis revealed journals prioritized publishing articles related to covid-19, as the mean time from submission to publication was shorter (43 days) than what has previously been observed. covid-19 related articles in the dermatology literature received more widespread attention as measured by the average aas (33 vs. 4 p<0.001) and were higher impact as measured by citation count (11 vs. 1, p<0.001) than non-covid-19 articles. conclusions: these findings demonstrates that dermatology research published regarding the covid19 pandemic received broader attention and were higher impact, suggesting the importance and influence of the pandemic for dermatology. introduction skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 483 publication process. further analysis sought to determine if articles related to the covid19 pandemic were more widely disseminated and had a higher impact than other articles published during the same period. we hypothesized that articles related to covid-19 would be more widely disseminated reflected by higher altmetric attention scores (aas) and garnered more impact as measured by the citation count during the pandemic. journal citation reports was used to select 15 dermatology journals with the highest impact factor in 2019 and all articles published in these journals in 2020 were evaluated.2 in total, 7,621 articles were identified and the aas, which is a weighted calculation of the attention an article receives online, was recorded for each article. a total of 519 (7%) articles related to covid-19 were identified by searching titles for "covid", "sars", "pandemic", "corona", "covid-19”, “2019 ncov”, “2019 novel coronavirus”, or "sars-cov-2". the kruskal-wallis test was used to assess aas and citations for covid-19 versus noncovid-19 related articles. for covid-19 related articles, we also assessed whether aas and citations varied by the type of article (editorial, original article, or guideline) and sub-specialty of dermatology to which the article pertained.3 continuous and categorical variables were assessed using mann-whitney and chi-squared tests with pre-determined level of significance p<0.05.3 after screening, 519 (7%) covid-19 related articles met criteria for inclusion. the journal of the american academy of dermatology (jaad) published the most articles related to the covid-19 pandemic (n=210, 12%; figure 1). the journal of the european academy of dermatology and venereology published the highest proportion of covid-related articles compared to all other journals (16% vs. all others %, p<0.001). a total of 40 countries were represented in covid-19 related dermatology literature, with the most frequent being the united states (32%), italy (17%), and spain (12%). an average of 3.6  4.5 (mean  sd) institutions and 6.2  5.3 authors contributed to each manuscript. sixty-five authors published more than one article, with four of those authors publishing more than five articles. thirty-three percent of all articles pertained to medical dermatology and 29.5% to general dermatology. surgical dermatology comprised the least number of articles, at 1% (figure 2). on average, articles had 768.9 words, 10.6 references, and were published 43 days after submission. most articles were published in april (16%), may (22%), and june (17%). the majority of articles were editorials (n=421, 81%), followed by original articles (n=81, 16%) and guidelines (n=10, 2%). original articles had the highest aas when compared to editorials and guidelines (86 vs. 23 vs. 16, p<0.001). when considering the various subspecialties within dermatology, the highest mean aas was observed for pediatric dermatology, however this was not significantly different compared to other subspecialties (p=0.97). additionally, covid-19 related articles had a significantly higher mean aas than articles not related to the pandemic (33 methods results skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 484 figure 1. number of covid-related articles published in the 15 dermatology journals with the highest impact factor (left) with respective percentage of total articles related to covid-19 (right) vs. 4 p<0.001; figure 3). while the pandemic has been a hot topic for discussion, the majority of covid-19 related articles (n=144, 28%) had an aas of zero, indicating the articles have received no attention on online news, blogs, search engines, and/or social media. figure 2. categorization of covid-related articles within dermatologic subgroups covid-19 related articles accumulated 5,802 citations in total and had a higher average number of citations per article compared to non-covid-19 related articles (11 vs. 1, p<0.001). of note, nearly a quarter of covid-19 related articles received zero citations while five articles accounted for a large number of citations (21%). there was no association between the number of citations and sub-specialty (p=0.20), or type of study conducted (p=0.18). the dermatology literature has been indelibly shaped by the covid-19 pandemic and has captured the attention of readers across the globe. the united states, italy, and spain were most frequently represented in the dermatology literature, which correlates with the severity of the pandemic discussion skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 485 in these countries in early 2020.4 most articles were published in april, may, and june after the first peak of covid-19 infection synonymous with submission during the initial wave of lockdowns in the united states and europe.5 figure 3. covid-related articles (mean aas = 33) were associated with a higher aas than non-covidrelated articles (mean aas = 4) (p<0.001) journals prioritized publishing articles about covid-19, as the time from submission to publication was shorter than what has previously been observed.5 many of these articles were editorials and commentaries, reflecting the necessary dialogue required to navigate the pandemic. further, covid-19 related articles in dermatology literature were more widely disseminated among online news sources and social media outlets accruing more attention than noncovid-19 articles, supporting our hypothesis that covid-19 articles have garnered more interest during the pandemic. thus, covid-19 publications commanded the dermatology literature in 2020 when other research activity was paused or limited. while the covid-19 pandemic appears to be subsiding in the united states secondary to widespread vaccination efforts, many areas of the world are still afflicted with high case burdens. this literature may serve of particular utility to dermatologists situated in these countries and are attempting to continually see patients despite risk of covid-19 transmission or are caring for patients with unique dermatologic sequelae from covid-19. for academic dermatologists, this study suggests that research energy, time, and resources were diverted to focus on the impact of covid-19. given that there is a limited pool of research funding, if concern for future pandemics or outbreaks remains high and grant money is redirected towards these causes, academic dermatologists may find increasing difficulty in securing funding for supporting scholarly activity. the increased number of editorials published during 2020 reflects the community of dermatology was effectively exchanging opinions and ideas during these unprecedented times. the significantly higher mean aas for covid-19 related articles compared to non-covid-19 related articles, suggests that the public was effectively receiving updates on the novel virus’ impact on the field of dermatology. further, articles related to covid-19 also fostered more impact as reflected by the significantly higher number of citations compared to non-covid-19 related articles. this study is limited as we solely examined articles published from 15 journals with the highest impact factor in 2019. this selection of journals may reduce the generalizability of these findings to the remainder of the dermatology literature. given the timing of the analysis, it is likely that more articles will continue to be published concerning the covid-19 pandemic and therefore this analysis only skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 486 includes a snapshot in time of the dynamic dermatology literature. further, any issues with manual screening of data or data entry introduces the possibility of misclassification of articles or errors in determining aas or citation count for each article. to mitigate these errors in screening and categorization, two independent reviewers collected the data and discrepancies were addressed by a third author until a consensus was achieved. in summary, the trends discussed in this article are not surprising given how pervasive the covid-19 pandemic has been on all aspects of medicine and are corroborated by analyses in other specialties.3 in a time of great uncertainty and upheaval, it is heartening to see how dermatologists worldwide have united to share their findings and experiences related to the global pandemic. conflict of interest disclosures: none funding: none corresponding author: carter j. boyd 222 east 41st street new york, ny, 10017 phone: (212) 355-5779 fax: 202-221-3815 email: carterjosephboyd@gmail.com references: 1. wollina u. challenges of covid-19 pandemic for dermatology. dermatol ther. 2020;33(5):e13430. doi:10.1111/dth.13430 2. thomley, m. e., preda-naumescu, a., boyd, c. j., & mayo, t. (2020). analyzing the relationship between altmetric score and literature citations in the dermatology literature. skin the journal of cutaneous medicine, 4(6), 497–505. https://doi.org/10.25251/skin.4.6.2 3. hemal k, boyd cj, cuccolo ng, saadeh pb. chronicling the covid-19 pandemic through the plastic surgery literature. j plast reconstr aesthet surg. 2021 feb 5:s17486815(21)00056-5. doi: 10.1016/j.bjps.2021.01.013. epub ahead of print. pmid: 33582052; pmcid: pmc7863790. 4. cumulative trends. johns hopkins coronavirus resource center website. published 2020. accessed march 18. https://coronavirus.jhu.edu/data/cumulative-cases 5. toroser d, carlson j, robinson m, et al. factors impacting time to acceptance and publication for peer-reviewed publications. curr med res opin. 2017;33(7):1183-1189. doi:10.1080/03007995.2016.1271778 6. altmetric attention score. (2021, march 10). retrieved march 22, 2021, from https://help.altmetric.com/support/solutions/article s/6000233311-how-is-the-altmetric-attentionscore-calculated#:~:text=the%20altmetric%20attention%20scor e%20for,attention%20that%20it%20has%20recei ved.&text=the%20score%20is%20derived%20fr om,up%20for%20a%20research%20output conclusion https://www.google.com/search?q=phone+number+nolan+karp&rlz=1c1wnoo_enus952us955&oq=phone+number+nolan+karp&aqs=chrome..69i57.4014j1j7&sourceid=chrome&ie=utf-8 patient tolerability of tazarotene foam, 0.1%, and impact on patient compliance patient perception of vehicle and how this influences adherence to topical treatment regimens steven r. feldman md, faad; rhonda schreiber bsn, ms; kaytiana crane bs; madelyn comito difficulties with patient adherence to previously available topical formulations of calcipotriene are well documented and prescribers have long sought ways to improve patient compliance with prescribed treatment regimens. patients have positive perceptions of the foam vehicle attributes, strong preference for the foam vehicle compared to previously tried medications, and a 22% greater reported likelihood of complying with prescribed treatment where foam is included. the foam vehicle may lead to better compliance and outcomes for patients suffering from psoriasis. references: 1. wolf-henning boehncke, michael p schön. lancet 2015; 386: 983–94. published online may 27, 2015. http://dx.doi.org/10.1016/s0140-6736(14)61909-7. 2. menter a, korman nj, elmets ca, feldman sr, gelfand jm, gordon kb,et al. guidelines of care for the management of psoriasis and psoriatic arthritis. section 3. guidelines of care for the management and treatment of psoriasis with topical therapies. j am acad dermatol. 2009 apr;60(4):643-59. 3. eastman wj, malahias s, delconte j, dibenedetti d. cutis. 2014 jul;94(1):46-53. 4. data on file; mayne pharma. disclosures: dr. feldman is a paid consultant at mayne pharma. mrs. schreiber, ms. crane, and ms. comito are employees of mayne pharma. this presentation was sponsored by mayne pharma • two identically designed, 8-week, blinded, multicenter, parallel group clinical trials were conducted with 659 subjects with mild to moderate plaque-type psoriasis randomized in a 2:1 ratio to topical calcipotriene foam, 0.005%, (n=437) or vehicle foam (n=222) • subjects ≥ 12 years with mild to moderate plaque psoriasis involving 2-20% of body surface areas (bsa) • foam was applied morning and evening or 8 weeks to lesions on the body, using the smallest amount of the product required to completely cover all lesions • lesions of the scalp or face were excluded • at the final study visit a patient questionnaire was administered regarding formulation attributes, preference for treatment vehicle, and intent to adhere to treatment instructions • questionnaire results from both phase iii trials have been integrated for analysis and presentation here conclusions methods results 58% 29% 59% 29% 5… 27% 58% 28% 59% 29% 59% 30% 59% 26% 39% 16% 0% 10% 20% 30% 40% 50% 60% 70% percent of patients rating foam attributes as excellent or good excellent good fair poor very poor 49% 27% 46% 22% 42% 20% 40% 20% 32% 13% 0% 10% 20% 30% 40% 50% 60% 70% percentage of patients who rated the foam vehicle as better and much better than previously tried medications much better better about the same worse much worse • psoriasis can lead to long lasting psychological, social, and physical complications. • the majority of cases can be treated with topical therapies, however poor adherence negatively impacts treatment success.2,3 • vehicle attribute influence adherence.3 • calcipotriene foam, 0.005%, is a safe and effective steroid-free vitamin d3 analog for plaque psoriasis of the scalp and body.4 • we assessed patient preference for attributes of both active and vehicle foams and how these preferences impacted patient intentions to comply with prescribed treatment plans. introduction if you were asked by your doctor to put medicine on your skin everyday including each morning and night for 8 weeks, how likely would you be to follow these instructions? the foam was rated the highest compared to the other vehicles, with 86% of study participants stating that they would comply between 75-100% of the time over an 8 week treatment course. the foam rated 22% higher than the next highest rated vehicle. please rate the foam on each of the following; easy to apply, spreadability, absorbs quickly, lack of stickiness, fragrance free, does not feel greasy, lack of residue, and moisturizing: both the active foam and vehicle rated excellent or good with greater than 80% of subjects on all formulation and application attributes, except moisturizing, where 55% of subjects rated the foam as excellent or good. please rate the following qualities of the foam, compared to the other skin medicines you have used in the past: 77% of subjects had used creams previously, 68% had used ointments, 53% lotions, 42% gels, and 39% had used solutions previously. the foam vehicle rated strongly overall in all qualities and the active calcipotriene, 0.005%, foam ranked consistently better than the foam vehicle alone 86% 64% 51% 47% 32% 31% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% foam cream ointment lotion solution gel predicted compliance rate >75% for 8 weeks integrated intent to treat analysis n=659, n(%) 100% 75-99% 50-74% 25-49% < or = 24% foam 384 (58) 180 (27) 19 (3) 3 (<1) 10 (2) cream 217 (33) 208 (32) 81 (12) 16 (2) 8 (1) ointment 172 (26) 162 (25) 92 (14) 43 (7) 18 (3) gel 119 (18) 88 (13) 62 (9) 29 (4) 384 12 (2) lotion 153 (23) 156 (24) 40 (6) 21 (3) 4 (1) solution 122 (19) 86 (13) 51 (8) 16 (2) 8 (1) integrated intent to treat analysis n=659, n(%) easy to apply excellent good fair poor very poor calcipotriene foam 0.005% 263 (40) 120 (18) 26 (4) 6 (1) 2 (<1) vehicle foam 132 (20) 58 (9) 14 (2) 5 (1) 1 (<1) speadability calcipotriene foam 0.005% 283 (43) 106 (16) 23 (3) 2 (<1) 1 (<1) vehicle foam 135 (20) 59 (9) 11 (2) 3 (<1) 0 (0) absorbs quickly calcipotriene foam 0.005% 228 (35) 140 (21) 31 (5) 14 (2) 3 (<1) vehicle foam 115 (17) 64 (10) 25 (4) 6 (1) 0 (0) lack of stickiness calcipotriene foam 0.005% 259 (39) 123 (19) 22 (3) 3 (<1) 3 (<1) vehicle foam 127 (19) 60 (9) 13 (2) 3 (<1) 2 (<1) fragrance free calcipotriene foam 0.005% 287 (44) 99 (15) 17 (3) 0 (0) 0 (0) vehicle foam 145 (22) 47 (7) 14 (2) 1 (<1) 0 (0) does not feel greasy calcipotriene foam 0.005% 263 (40) 125 (19) 21 (3) 5 (1) 3 (<1) vehicle foam 130 (20) 69 (10) 8 (1) 2 (<1) 1 <1) lack of residue calcipotriene foam 0.005% 209 (32) 140 (21) 54 (8) 11 (2) 3 (<1) vehicle foam 91 (14) 80 (12) 26 (4) 8 (1) 4 (1) moisturizing calcipotriene foam 0.005% 100 (15) 158 (24) 115 (17) 28 (4) 14 (2) vehicle foam 31 (5) 73 (11) 64 (10) 27 (4) 8 (1) integrated intent to treat analysis n=659, n(%) disappears quickly after application much better better about the same worse much worse calcipotriene 0.005% foam 215 (33) 112 (17) 49 (7) 20 (3) 5 (1) vehicle foam 103 (16) 72 (11) 20 (3) 8 (1) 3 (<1) easily applies to large bsa calcipotriene 0.005% foam 182 (28) 121 (18) 62 (9) 7 (1) 4 (1) vehicle foam 85 (13) 59 (9) 38 (6) 7 (1) 1 (<1) easier to use calcipotriene 0.005% foam 167 (25) 108 (16) 80 (12) 39 (6) 7 (1) vehicle foam 70 (11) 59 (9) 51 (8) 19 (3) 5 (1) continue adls immediately after applying calcipotriene 0.005% foam 178 (27) 87 (13) 114 (17) 15 (2) 1 (<1) vehicle foam 82 (12) 50 (8) 62 (9) 8 (1) 1 (<1) leaves skin feeling soft calcipotriene 0.005% foam 116 (18) 97 (15) 150 (23) 24 (4) 8 (1) vehicle foam 39 (6) 44 (7) 81 (12) 33 (5) 6 (1) patient perception of vehicle and how this influences adherence to topical treatment regimens�steven r. feldman md, faad; rhonda schreiber bsn, ms; kaytiana crane bs; madelyn comito objective ● atopic dermatitis is a chronic inflammatory disease characterized by eczematous skin lesions and multiple symptoms, including pruritus, sleep disturbance, and depression1-4 ● tralokinumab is a high-affinity, fully human monoclonal antibody designed to specifically neutralize interleukin-13, a key driver of the underlying inflammation in atopic dermatitis5-7 ● phase 3 trials have established the efficacy and safety of tralokinumab for up to 52 weeks in adult patients with moderate-to-severe atopic dermatitis8,9 ● an ongoing, open-label extension trial, ecztend (nct03587805), is investigating the long-term safety and efficacy of tralokinumab in patients with atopic dermatitis who participated in previous tralokinumab trials ● to present interim ecztend efficacy data collected through april 30, 2020 from a patient cohort receiving tralokinumab for at least 56 weeks conclusions ● in this ecztend interim analysis of the week 56 cohort, tralokinumab 300 mg q2w plus optional tcs demonstrated sustained long-term improvements in itch, sleep, and the extent and severity of atopic dermatitis up to week 56, with maintenance of robust easi response rates (61% of patients achieved easi-90 at week 56) ● overall, tralokinumab plus optional tcs was well tolerated in patients enrolled in ecztend at data cut-off, with a safety profile consistent with the parent trials long-term improvements observed in tralokinumab-treated patients with moderate-to-severe atopic dermatitis: an ecztend interim analysis andrew blauvelt,1 jean-philippe lacour,2 darryl toth,3 vivian laquer,4 stefan beissert,5 andreas wollenberg,6 pedro herranz,7 andrew pink,8 ketty peris,9 stine fangel,10 hidehisa saeki11 patient demographics total (n=1174) parent trial, n (%) ecztra 1 (52-week monotherapy) 450 (38.3) ecztra 2 (52-week monotherapy) 293 (25.0) ecztra 3 (32-week combination therapy) 282 (24.0) ecztra 5 (16-week monotherapy) 149 (12.7) median (iqr) age, years 38 (27.0-50.0) male, n (%) 675 (57.5) region, % north america 46.2 europe 46.5 japan 7.3 median (iqr) duration of ad at baseline, years 27 (18.0-40.0) median (iqr) bsa at parent trial baseline, % 44.5 (30.0-67.0) median (iqr) time from last dose in parent trial, days 36 (15.0-85.0) baseline characteristics all parent trials ecztend median (iqr) easi score 26.6 (19.7-37.2) 4.7 (1.8-11.7) median (iqr) iga score 3.0 (3.0-4.0) 2.0 (1.0-3.0) median (iqr) dlqi score 17.0 (11.0-22.0) 5.0 (2.0-10.0) median (iqr) scorad 67.4 (59.8-78.0) 30.2 (18.7-45.0) median (iqr) poem 24.0 (20.0-27.0) 12.0 (6.0-18.0) table 1. baseline characteristics of all patients from parent trials ecztra 1, 2, 3, and 5 enrolled in ecztend at data-cut off reason for withdrawal, n (%)a total (n=1174) total patients withdrawing from the study 139 (11.8) adverse event 19 (1.6) lost to follow-up 29 (2.5) withdrawal by patient 16 (1.4) lack of efficacy (investigator or patient opinion) 24 (2.0) otherb 51 (4.3) table 2. withdrawal from ecztend 60 50 40 30 20 10 0 week 56 locfc (n=612) week 56 nrid (n=612) r e sp o n d e rs , % week 56 observedb (n=513) 49.7% 47.1% 41.7% figure 5. iga 0/1 response rate at week 56 with tralokinumab (week 56 cohorta) 1oregon medical research center, portland, or, usa; 2department of dermatology, university hospital of nice côte d’azur, nice, france; 3probity medical research, windsor, ontario, canada; 4first oc dermatology, fountain valley, ca, usa; 5department of dermatology, university of dresden, dresden, germany; 6department of dermatology and allergology, ludwig-maximilian university of munich, munich, germany; 7department of dermatology, hospital universitario la paz, madrid, spain; 8st john’s institute of dermatology, guy’s and st thomas’ hospitals, london, uk; 9institute of dermatology, catholic university of the sacred heart, rome, italy; 10leo pharma a/s, ballerup, denmark; 11department of dermatology, nippon medical school, tokyo, japan introduction results methods figure 3. patient cohorts in ecztend interim analysis (april 30, 2020 data cut-off) safety analysis set (n=1174) week 56 cohort (n=612) 2-year cohort (n=345) patients previously treated with tralokinumab monotherapy for 52 weeks in ecztra 1 and 2, followed by 56 weeks of treatment in ecztend all patients who reached the 1-year time point (week 56) or would have reached that time point had they not discontinued earlier all patients transferred from ecztra 1, 2, 3, and 5 figure 4. mean easi and percentage change up to week 56 with tralokinumab (week 56 cohorta) enrollment time in ecztend, weeks total (n) 612 612 591 585 571 565 554 542 513 total (n) 612 612 591 585 571 565 554 542 513 m e a n e a s i p e rc e n ta g e c h a n g e f ro m p a re n ttr ia lb a se lin e 0bp 42 8 12 16 24 32 40 48 56 0bp 42 8 12 16 24 32 40 48 56 0 –90 –80 –70 –60 –50 –40 –30 –20 –10 –100 m e a n e a s i 35 30 25 20 15 10 5 0 enrollment time in ecztend, weeks mean (sd) –86.8 (17.5) median –93.6 q1; q3 –98.5; –81.4 mean (sd) 4.2 (6.1) median 1.8 q1; q3 0.4; 5.6 figure 7. mean worst weekly pruritus nrs and eczema-related weekly sleep nrs scores up to week 56 with tralokinumab (week 56 cohorta) total (n) 609 592 585 571 563 555 541 514 total (n) 609 592 585 571 563 555 541 514 worst weekly pruritus nrs by visit m e a n s co re 10 9 8 7 6 5 4 3 2 1 0 10 9 8 7 6 5 4 3 2 1 0 week eczema-related weekly sleep nrs by visit m e a n s co re week mean (sd) 3.3 (2.6) median 3.0 q1; q3 1.0; 5.0 mean (sd) score at parent trial baselineb 7.7 (1.4) mean (sd) 2.0 (2.4) median 1.0 q1; q3 0.0; 3.0 mean (sd) score at parent trial baselineb 6.9 (2.1) 0 42 8 16 24 32 40 48 56 0 42 8 16 24 32 40 48 56 figure 1. patient recruitment from parent trialsa h1 h2 h1 h2 h1 h2 h1 h2 h1 h2 h1 h2 h1 h2 h1 h2 2017 2018 2019 2020 2021 2022 2023 2024 fpfv to lplv fpfv: september 18, 2018 ecztra 1 (monotherapy) ecztra 2 (monotherapy) ecztra 3 (tcs combination) ecztra 5 (vaccine) ecztra 6 (adolescent) ecztra 7 (csa failure/intolerantb) ecztra 8 (tcs combination) traski (iis) ecztend (lte) ecztra 4 (ddi) figure 2. ecztend trial design weeks from first treatment in ecztend site visit. iga, easi, scorad, worst weekly pruritus nrs, eczema-related sleep nrs, use of topical treatment screening and follow-up visits home use training poem, dlqi/cdlqi, eq-5d-5lb ada/pharmacokinetics measurement tcs use allowed screening period visit schedule until end of may 2021a sfu 16 weeks after last imp 2485640322416 484 8-2 0 figure 6. proportion of patients achieving easi-50, easi-75, and easi-90 at week 56 with tralokinumab (week 56 cohorta) r e sp o n d e rs , % 513 100 80 60 40 20 0 612 612 513 612 612 513 612 612 easi-50 easi-75 easi-90 n week 56 observed week 56 locfc week 56 nrid b figure 8. proportion of patients achieving easi-50, easi-75, and easi-90 with tralokinumab at week 56 (52 weeks in parent study plus 56 weeks in ecztenda) 2-year (108-week) tralokinumab arms observedb 2-year (108-week) tralokinumab arms locfc 291 345 easi-50 291 345 easi-75 291 345 easi-90 r e sp o n d e rs , % 100 80 60 40 20 0 n 52 weeks 56 weeks ecztend (lte) ecztra 1 (tralokinumab) ecztra 2 (tralokinumab) table 3. overall safety profile of tralokinumab ad safety pool (ecztra 1, 2, 3, and 5, phase 2b)a initial treatment period ecztend safety analyses setb trial start to april 30, 2020 tralokinumab q2w  tcs (n=105, pye=473.19) placebo q2w  tcs (n=80, pye=193.1) tralokinumab q2w 1 optional tcs (n=1174, pye=1235.7) n adj. % adj. r n adj. % adj. r n % r all adverse events 1080 65.7 639.5 449 67.2 678.3 844 71.9 237.8 serious adverse events 37 2.1 7.4 18 2.8 11.9 55 4.7 4.8 severity mild 881 53.2 429.8 326 49.0 391.0 695 59.2 158.2 moderate 518 31.5 189.5 258 39.0 254.3 435 37.1 72.1 severe 77 4.6 20.2 40 6.3 33.0 62 5.3 7.5 leading to drug withdrawal 38 2.3 9.9 20 2.8 13.3 28 2.4 2.3 most frequently reported adverse events (>5% of patients) viral upper respiratory tract infection (most commonly reported as common cold) 256 15.7 65.1 78 12.2 53.5 250 21.3 29.3 atopic dermatitis 272 15.4 68.0 167 26.2 139.7 158 13.5 20.6 upper respiratory tract infection 92 5.6 20.8 33 4.8 18.5 83 7.1 9.1 safety areas of interest conjunctivitis, including conjunctivitis, allergic conjunctivitis, bacterial conjunctivitis, viral conjunctivitis, and atopic conjunctivitis 126 7.5 29.0 21 3.2 12.3 65 5.9 6.9 patients ● ecztend is an ongoing, up to 268-week, open-label, single-arm, multicenter, long-term extension trial in patients with atopic dermatitis who participated in parent tralokinumab trials (ecztra 1-8 and traski) (figure 1) key inclusion criteria — completed treatment period(s) in a tralokinumab parent trial (ecztra 1-8 or traski) without any safety concerns — complied with the clinical trial protocol in the parent trial — able and willing to self-administer tralokinumab, or have it administered by a caregiver, at home after the initial 3 injection visits at trial site — applied a stable dose of emollient (minimum twice daily) for at least 14 days before baseline ecztend trial design ● patients received subcutaneous tralokinumab 300 mg every 2 weeks (q2w) plus optional topical corticosteroids (tcs) after a 300 mg or 600 mg loading dose of tralokinumab (figure 2) ecztend trial design ● study primary and secondary endpoints: — number of adverse events from baseline up to week 268 — investigator’s global assessment (iga) score of 0/1 from week 16 to week 248 — eczema area and severity index reduction of at least 75% (easi-75) a from week 16 to week 248 week 56 interim analysis: — included patients from parent trials ecztra 1, 2, 3, and 5 enrolled in ecztend at least 60 weeks before data cut-off (n=612) — efficacy outcomes assessed include: • mean easi up to week 56 • iga 0/1 response rate at week 56 • easi-50, easi-75, easi-90,a and easi 7 response rates at week 56 • mean worst weekly pruritus numeric rating scale (nrs) and eczema-related weekly sleep interference nrs scores up to week 56 disclosures andrew blauvelt has served as a scientific adviser and/or clinical study investigator for abbvie, abcentra, aligos, almirall, amgen, arcutis, arena, athenex, boehringer ingelheim, bristol myers squibb, dermavant, eli lilly, evommune, forte, galderma, incyte, janssen, landos, leo pharma, novartis, pfizer, rapt, regeneron, sanofi genzyme, sun pharma, and ucb pharma. jean-philippe lacour has received grants or honoraria as an investigator, advisory board member, or speaker from abbvie, amgen, boehringer ingelheim, celgene, dermira, eli lilly, janssen, leo pharma, novartis, pfizer, regeneron, and sanofi darryl toth has served as an investigator for abbvie, amgen, arcutis, boehringer ingelheim, bond avillion, bristol myers squibb, celgene, centocor, dermira, eli lilly, galderma, gsk, incyte, janssen, leo pharma, merck, novartis, pfizer, regeneron, ucb pharma, and valeant. vivian laquer has received grants from abbvie, eli lilly, galderma, leo pharma, and novartis. stefan beissert has served as an advisory board member for or received speaker honoraria from abbvie deutschland & co, actelion pharmaceuticals, almirall hermal, amgen, bristol myers squibb, celgene, galderma, gsk, hexal-sandoz, janssencilag, la roche-posay, leo pharma, lilly deutschland, menlo therapeutics, merck sharp & dohme, novartis, pfizer, sanofi-aventis deutschland, and ucb pharma. andreas wollenberg has received grants, personal fees, or nonfinancial support from abbvie, almirall, beiersdorf, bioderma, chugai, eli lilly, galapagos, galderma, hans karrer, leo pharma, l’oréal, maruho, medimmune, novartis, pfizer, pierre fabre, regeneron, santen, and sanofi-aventis. pedro herranz has served as a consultant, speaker, or investigator for amgen, eli lilly, janssen, leo pharma, novartis, parexel, pfizer, and sanofi. andrew pink reports personal fees and nonfinancial support from leo pharma, novartis, and ucb pharma; and personal fees from abbvie, almirall, eli lilly, janssen, la roche-posay, and sanofi. ketty peris reports grants or personal fees for participation in advisory boards from abbvie, almirall, eli lilly, galderma, janssen, leo pharma, novartis, pierre fabre, sanofi, and sun pharma. stine fangel are employee of leo pharma. hidehisa saeki has received lecture fees from kyorin, kyowa kirin, leo pharma, maruho, mitsubishi tanabe, sanofi, taiho, and tokiwa; and scholarship donations from esai, maruho, mitsubishi tanabe, and torii. the ecztend study is sponsored by leo pharma. references 1. weidinger s, novak n. lancet. 2016;387:1109-22. 2. eckert l, et al. j am acad dermatol. 2017;77:274-9.e273. 3. silverberg ji, et al. ann allergy asthma immunol. 2018;121:340-7. 4. dalgard fj, et al. j invest dermatol. 2015;135:984-91. 5. bieber t. allergy. 2020;75:54-62. . tsoi lc, et al. j invest dermatol. 2019;139:1480-9. 7. popovic b, et al. j mol biol. 2017;429:208-19. 8. wollenberg a, et al. br j dermatol. 2021;184:437-49. 9. silverberg ji, et al. br j dermatol. 2021;184:450-63. 10. leshem ya, et al. br j dermatol. 2015;172:1353-7. 11. hongbo y, et al. j invest dermatol. 2005;125:659-64. aeasi-50, easi-75, and easi-90 are calculated based on baseline easi in parent trial. patient cohorts (figure 3) baseline characteristics ● at ecztend baseline, patients had mild atopic dermatitis, based on median easi score, and the median dermatology life quality index score indicated that atopic dermatitis had a small effect on their quality of life10,11 (table 1) ● based on easi, the overall ecztend cohort and week 56 cohort had similar baseline disease severity withdrawal from ecztend ● analysis includes all patients from parent trials ecztra 1, 2, 3, and 5 enrolled in ecztend at data cut-off (april 30, 2020) (table 2) ● the median (interquartile range) duration from first tralokinumab dose to last visit at data cut-off (follow-up period) was 58.1 (46.4-66.3) weeks analysis includes all patients from parent trials ecztra 1, 2, 3, and 5 enrolled in ecztend at data cut-off (april 30, 2020). adata are subject to change as the ongoing ecztend study progresses; bwithdrawal from ecztend due to pregnancy, protocol deviation (concomitant medication/eligibility), physician decision, or administrative reasons (patient moved/relocated/busy/transportation issues/ personal reasons). mean easi up to week 5 with tralokinumab ● mean easi reduced from a score equivalent to moderate-to-severe atopic dermatitis at parent trial baseline to mild-to-moderate atopic dermatitis at ecztend baseline, and was sustained over time in ecztend (figure 4) iga 0/1 response rate at week 5 with tralokinumab ● a high level of iga 0/1 response rate was sustained with tralokinumab at week 56 in ecztend (figure 5) aweek 56 cohort included all patients from parent trials ecztra 1, 2, 3, and 5 enrolled at least 60 weeks before data cut-off (april 30, 2020); bpatients who reached week 56; cmissing data imputed using locf; dmissing data imputed as non-response. iga, investigator’s global assessment; locf, last observation carried forward; nri, non-responder imputation. proportion of patients achieving easi-50, easi-75, and easi-90 at week 5 with tralokinumab ● a high level of easi-50, easi-75, and easi-90 response rates were sustained with tralokinumab at week 56 in ecztend (figure ) — 61% of patients achieved easi-90 at week 56 ● at week 56, 79.7% of patients achieved easi 7, a category corresponding to mild atopic dermatitis mean worst weekly pruritus nrs and eczema-related weekly sleep nrs scores up to week 5 with tralokinumab ● mean worst weekly pruritus nrs and eczema-related weekly sleep nrs scores were sustained over time in ecztend with tralokinumab (figure 7) — patients achieved scores equivalent to mild-to-moderate itch and mild sleep interference at week 56 proportion of patients achieving easi-50, easi-75, and easi-90 at week 5 with tralokinumab ● patients treated with tralokinumab for a total of 2 years at ecztend data cut-off demonstrated high levels of easi-50, easi-75, and easi-90 response rates, which were consistent with the overall week 56 cohort (figure 8) safety ● the overall safety profile of tralokinumab was consistent with parent trials (table 3) ad, atopic dermatitis; bsa, body surface area; dlqi, dermatology life quality index; easi, eczema area and severity index; iga, invstigator’s global assessment; iqr, interquartile range; poem, patient-oriented eczema measure; scorad, scoring atopic dermatitis. aprevious treatment regimens in parent trials included tralokinumab q2w, q4w, or placebo 6 tcs; bstudy in patients with atopic dermatitis who are not adequately controlled with or have contraindications to oral csa. csa, cyclosporine; ddi, drug–drug interaction; fpfv, first patient first visit; iis, investigator-initiated study; lplv, last patient last visit; lte, long-term extension; q2w, every 2 weeks; q4w, every 4 weeks; tcs, topical corticosteroids. aafter may 2021, some site visits will be switched to telephone visits; bpatients from the parent trial ecztra 6 will not perform the eq-5d-5l. ada, anti-drug antibodies; cdlqi, children’s dermatology life quality index; dlqi, dermatology life quality index; easi, eczema area and severity index; eq-5d-5l, euroqol 5-dimension health questionnaire 5-level; iga, investigator’s global assessment; imp, investigational medicinal product; nrs, numeric rating scale; poem, patient-oriented eczema measure; q2w, every 2 weeks; scorad, scoring atopic dermatitis; sfu, safety follow-up; tcs, topical corticosteroids. aweek 56 cohort included all patients from parent trials ecztra 1, 2, 3, and 5 enrolled at least 60 weeks before data cut-off (april 30, 2020); bpatients who reached week 56; cmissing data imputed using locf; dmissing data imputed as non-response. easi, eczema area and severity index; locf, last observation carried forward; nri, non-responder imputation. aweek 56 cohort included all patients from parent trials ecztra 1, 2, 3, and 5 enrolled at least 60 weeks before data cut-off (april 30, 2020). data were analyzed as observed bparent trial baseline value based on patients from ecztra 1, 2, and 3 only. nrs, numeric rating scale; sd, standard deviation. a2-year cohort included all patients who received treatment with tralokinumab for 52 weeks in parent trials ecztra 1 and 2, followed by treatment with tralokinumab for 56 weeks in ecztend at data cut-off (april 30, 2020); bpatients who reached week 56; cmissing data imputed using locf. easi, eczema area and severity index; locf, last observation carried forward; lte, long-term extension. aincludes patients from parent trials ecztra 1, 2, 3, 5, and phase 2b; bincludes all patients from parent trials ecztra 1, 2, 3, and 5 enrolled in ecztend at data cut-off (april 30, 2020). %, percentage of patients with ≥1 event; ad, atopic dermatitis; adj. %, adjusted percentage calculated using cochran–mantel–haenszel weights; adj. r, adjusted rate calculated using cochran–mantel–haenszel weights; pye, patient-years of exposure; q2w, every 2 weeks; r, rate (number of adverse events divided by patient-years of exposure multiplied by 100); tcs, topical corticosteroids. aweek 56 cohort included all patients from parent trials ecztra 1, 2, 3, and 5 enrolled at least 60 weeks before data cut-off (april 30, 2020). data were analyzed as observed. bp, parent trial baseline; easi, eczema area and severity index; sd, standard deviation. originally presented at american academy of dermatology (aad) vmx, april 23-25, 2021. acknowledgements: medical writing support was provided by prescott medical communications group (chicago, il) with financial support from ortho dermatologics; ortho dermatologics is a division of bausch health us, llc • presented at fall clinical dermatology conference • october 21-24, 2021 • las vegas, nv references 1. tanghetti ea, et al. j dermatol treat. 2019:1–8. 2. tanghetti ea, et al. j drugs dermatol. 2019;18(6):542–548. 3. chandraratna ras. j amer acad dermatol. 1997;18(6): 542–548. 4. finzl e, et al. am j pathol. 1992;140(6):1463–1471. author disclosures zoe draelos received funding from ortho dermatologics to conduct the research presented here. emil tanghetti has served as speaker for novartis, ortho dermatologics, sun pharma, lilly, galderma, abbvie, and dermira; served as a consultant/clinical studies for hologic, ortho dermatologics, and galderma; and is a stockholder for accure. linda stein gold has served as investigator/consultant or speaker for ortho dermatologics, leo pharma, dermavant, incyte, novartis, abbvie, pfizer, sun pharma, ucb, arcutis and lilly. hilary baldwin has served as advisor, investigator, and on speakers’ bureaus for almirall, cassiopea, foamix, galderma, ortho dermatologics, sol gel, and sun pharma. leon kircik has acted as an investigator, advisor, speaker, and consultant for ortho dermatologics. eric guenin is an employee of ortho dermatologics and may hold stock and/or stock options in its parent company. introduction and formulation � tazarotene 0.045% lotion was developed using polymeric emulsion technology to provide uniform and rapid distribution of the active ingredient and hydrating excipients at the skin surface and to efficiently deliver tazarotene into skin1 � tolerability may be improved by the vehicle design and the homogenous nature of the delivery as well as the lower dose of tazarotene used compared with all other tazarotene formulations2 polymeric emulsion technology for tazarotene 0.045% lotion ① polymeric matrix holds water and water-soluble hydrating agents within a 3-d mesh ② droplets of tazarotene and oil-soluble moisturizing agents held apart by the 3-d mesh ③ 3-d mesh allows for uniform distribution of tazarotene and moisturizing agents 25-50 μm 1-2 μm ① ② ③ skin deposition: tazarotene 0.045% lotion vs tazarotene 0.1% cream draelos zd and draelos mm. j drugs dermatol. 2021; in press. results � 10 female white participants aged 19–59 years completed the study � at 6 hours post application, most tazarotene remained on the skin surface, as indicated by the higher tazarotene concentrations recovered from superficial (tape strip 2) versus deeper skin layers (tape strip 20) � concentration of tazarotene was approximately 2-fold higher for 0.1% cream vs 0.045% lotion at both superficial and deep skin layers, but the absolute difference drastically decreased in deeper layers tazarotene 0.045% lotion tazarotene 0.1% cream 2 4 6 8 10 12 14 16 18 20 ta pe s tr ip n um be r superficial dermis d ee pe r s ki n la ye rs d ee pe r s ki n la ye rs stratum corneum • higher tazarotene concentrations remained at super�cial vs deeper layers • difference in concentration between formulations drastically decreased in deeper layers cream minus lotion (µg/ml) 0.80 0.42 0.31 0.20 0.19 0.09 0.10 0.12 0.07 0.09 dot area corresponds to tazarotene concentration. skin layers shown for illustrative purposes only. exact location of tape strip sampling within the skin is unknown. lc-ms, liquid chromatography-mass spectrometry. tazarotene 0.045% lotion for acne: formulation, application characteristics, and clinical efficacy and safety zoe d draelos, md1; emil a tanghetti, md2; linda stein gold, md3; hilary baldwin, md4,5; leon h kircik, md6,7,8; eric guenin, pharmd, phd, mph9 1dermatology consulting services, pllc, high point, nc; 2center for dermatology and laser surgery, sacramento, ca; 3henry ford hospital, detroit, mi; 4the acne treatment and research center, brooklyn, ny; 5robert wood johnson university hospital, new brunswick, nj; 6indiana university school of medicine, indianapolis, in; 7physicians skin care, pllc, louisville, ky; 8icahn school of medicine at mount sinai, new york, ny; 9ortho dermatologics,* bridgewater, nj *ortho dermatologics is a division of bausch health us, llc spreadability: tazarotene 0.045% lotion vs trifarotene 0.005% cream � skin coverage with tazarotene 0.045% lotion was compared to trifarotene 0.005% cream in a double-blind split-body study of 30 healthy adults (aged 18-59 years) � each product (0.1 ml) was applied to a 10 cm wide area on one side of participants’ backs until it would no longer spread; area of spread was then determined results � the average area of spread for tazarotene 0.045% lotion and trifarotene 0.005% cream was 167.0 and 130.3 cm2, respectively (difference = 36.7 cm2; p<0.001) participant example tazarotene 0.045% lotion trifarotene 0.005% cream conclusions � tazarotene 0.045% lotion utilizes polymeric emulsion technology to enhance hydration, moisturization, and skin barrier function � this easy-to-apply lotion, with sensory and aesthetic properties preferred by patients, appears to have greater skin coverage compared with trifarotene cream � there is superior tolerability of tazarotene 0.045% lotion versus tazarotene 0.1% cream, with similar clinical efficacy • tazarotene is a potent activator of retinoic acid gamma receptors (enriched throughout skin3,4); thus, lower levels in deeper skin with tazarotene 0.045% lotion vs 0.1% cream are sufficient for clinical effect • superior tolerability of tazarotene 0.045% lotion vs 0.1% cream may be due to lower drug concentration at superficial epidermal layers � tazarotene 0.045% lotion is a beneficial treatment option for acne in patients aged 9 and older, delivered in an easy-to-spread formulation that can be applied to the face, back, and chest phase 2 study: tazarotene 0.045% lotion, tazarotene 0.1% cream, and vehicle tanghetti ea, et al. j drugs dermatol. 2019;18(6):542–548. � a total of 210 participants aged ≥12 years with moderate-to-severe acne (evaluator’s global severity score [egss] of 3 or 4) were randomized (2:2:1:1) to receive once-daily tazarotene 0.045% lotion, tazarotene 0.1% cream, lotion vehicle, or cream vehicle for 12 weeks results � tazarotene 0.045% lotion demonstrated significantly greater mean percent reductions in inflammatory and noninflammatory lesion counts vs vehicle at week 12 � rates of treatment-emergent adverse events (teaes), serious adverse events, and treatment-related teaes were lower with tazarotene 0.045% lotion compared with tazarotene 0.1% cream -20% 0% -40% -60% -80% -100% #( -63.8% in�ammatory lesions m e a n p e rc e n t c h a n g e f ro m b a se lin e t o w e e k 1 2 -60.0% -51.4% -56.9% nonin�ammatory lesions -54.1% -35.2% taz 0.045% lotion (n=69) itt population taz 0.1% cream (n=72) combined vehicle (n=69) teae summary, safety population taz 0.045% lotion (n=68) taz 0.1% cream (n=71) combined vehicle (n=67) any teae 14.7% 26.8% 13.4% any sae 0% 0% 0% any teae related to treatment 2.9% 5.6% 0% tazarotene 0.045% lotion: • signi�cantly superior to vehicle • comparable ef�cacy to cream • fewer adverse events than cream **p<0.01, ***p<0.001 vs combined vehicle. statistical comparison between taz 0.1% cream and combined vehicle was not conducted. at week 12, a greater percentage of tazarotene 0.045%-treated participants achieved treatment success versus combined vehicle (18.8% vs 10.1%), though this difference did not reach statistical significance. itt, intent to treat; sae, serious adverse event; taz, tazarotene; teae, treatment-emergent adverse event. drug concentration potential for irritation sufficient for efficacy superficial dermis stratum corneum patient preference tanghetti ea, et al. j dermatol treat. 2019;1–8. � healthy female participants aged 35–65 years (n=15) answered a questionnaire on the properties of the vehicle lotion for tazarotene 0.045% results � most participants (93–100%) responded favorably (strongly agree or agree) to all questions about the various attributes of the vehicle lotion after application my skin feels… the product… corneometry and transepidermal water loss (tewl) tanghetti ea, et al. j dermatol treat. 2019;1–8. � skin hydration and epidermal barrier maintenance with the vehicle lotion were assessed through corneometry and tewl (n=30) results � the vehicle lotion provided rapid and sustained increases in skin moisturization (left) and improved barrier function (right) skin moisturization assessment skin barrier assessment using corneometry (n=30) using tewl (n=30) 0 10 20 30 40 50 60 70 0 0.25 1 8 24 0 2 4 6 8 10 12 14 16 0 0.25 1 8 24 m e a n s co re s ± s d m e a n s co re s ± s d vehicle lotion untreated control hours hours vehicle lotion untreated control ***p<0.001 vs untreated control. sd, standard deviation. 1 2 3 4 post-application: tape strips applied and held for 10 sec using a controlled pressure plunger tape strips removed. first strip discarded; 20 additional strips taken at same sampling location (frozen until analysis) even-numbered tape strips processed and analyzed for tazarotene using lc-ms ~1 g of each product (blue and green) applied to square areas on each forearm 404 not found acknowledgements: medical writing support was provided by prescott medical communications group (chicago, il) with financial support from ortho dermatologics; ortho dermatologics is a division of bausch health us, llc • presented at fall clinical dermatology conference • october 21-24, 2021 • las vegas, nv therapeutic recommendations for the treatment of toenail onychomycosis in the us shari r lipner, md, phd1; warren s joseph, dpm2; tracey c vlahovic, dpm3; richard k scher, md1; phoebe rich, md4; mahmoud ghannoum, phd5; c ralph daniel, md6; boni elewski, md7 1department of dermatology, weill cornell medicine, new york, ny; 2arizona college of podiatric medicine, midwestern university, glendale, az; 3temple university school of podiatric medicine, philadelphia, pa; 4oregon health and science university, portland, or; 5case western reserve university, and university hospitals cleveland medical center, cleveland, oh; 6department of dermatology, university of mississippi medical center, jackson, ms; 7university of alabama at birmingham school of medicine, birmingham, al synopsis � onychomycosis—a fungal infection of the nail bed or plate—affects up to 14% of individuals in north america1,2 � it is undertreated and treatment is challenging as toenail growth can take up to 12 months or more, the nail plate may prevent drug penetration, and disease recurrence is common3-6 � national guidelines and consensus documents on onychomycosis diagnosis and treatment were last published more than 5 years ago in 2014 (british7) and 2015 (canadian1)—around the time that both topical efinaconazole and tavaborole were first approved in the us in 2014 • since then, more clinical data, post hoc analyses, meta-analyses, and fda-approved indications have become available for onychomycosis drugs • as such, updated medical guidance is needed objective and methods � to provide recommendations for the diagnosis and therapeutic treatment of toenail onychomycosis following a roundtable discussion with the authors on march 15, 2021 � included here is a decision tree for choosing appropriate medications based on disease severity and patient characteristics, as well as an example handout intended for patients on best practices to mitigate disease recurrence results diagnosis, testing, and clinical presentation � careful assessment and testing must be performed when diagnosing onychomycosis; nail dystrophy can be induced by other disorders, and many common conditions that can mimic onychomycosis should be ruled out (figure 1) � laboratory testing should also be performed to identify the infecting organism and exclude non-fungal conditions; figure 1 shows common options that are used in conjunction with clinical diagnosis recommended medications � the authors all agreed that treatment should be individualized for each patient based on nail involvement (number, surface area, thickness), infecting organism, patient characteristics (including comorbidities), current medications, biomechanics, cost/ availability/accessibility based on insurance, and patient preference � a decision tree to provide practical guidance on therapeutic recommendations in onychomycosis treatment developed by the authors is shown in figure 2 � therapeutic recommendations by drug are also detailed in figure 3 � among oral medications, terbinafine is most commonly used as first-line treatment, followed by fluconazole � among topical products, efinaconazole is ideal as first-line medication in pediatric patients, patients with less severe disease, and those with dermatophytomas � a topical medication was also recommended for use in combination with terbinafine or fluconazole and can be considered as maintenance therapy to prevent relapse � to improve outcomes, concurrent tinea pedis should be treated in all patients receiving topical therapy for onychomycosis figure 1. differential diagnosis decision tree no yes ≥1 clinical sign(s) of possible onychomycosis? • longitudinal ridging/splitting • onycholysis • subungual hyperkeratosis • nail plate thickening/crumbling • nail discoloration (yellow, brown, black, white) use ≥1 con�rmatory test(s) for onychomycosis: • dermoscopy as a preliminary test to evaluate nail dystrophy/roughness • histopathology (to distinguish other nail diseases, such as psoriasis) • fungal culture • periodic acid-schiff (pas) stain • potassium hydroxide (koh) • polymerase chain reaction (pcr) differential diagnoses that can cause nail deformity: • nail psoriasis • chronic nail trauma/mechanical issues • onychogryphosis • lichen planus • onycholysis • tumor (subungual malignant melanoma, bowen’s disease, �broma, melanoma) • viral warts • chronic dermatitis or paronychia • bacterial infection • subungual exostosis • subungual hematoma unable to con�rm onychomycosis: recheck diagnosis con�rmed onychomycosis: begin treatment (see figure 2) from lipner sr, et al. j drugs dermatol. 2021;20(10): doi:10.36849/jdd.6291. figure 2. decision tree on therapeutic recommendations for the treatment of confirmed onychomycosis population pregnant/lactating adults clinical presentation pediatric aged ≥65 years, concomitant medications, or comorbidities aged <65 years and relatively healthy no current recommendations topical efinaconazole (check entire family for infection) milda topical efinaconazole patients aged ≥65 years,diabetic, peripheral vascular disease, or immunocompromised topical treatmentb + oral terbinafine or oral fluconazole concomitant meds topical treatmentb +/oral terbinafine or oral fluconazole concurrent nail psoriasis treat onychomycosis first by clinical presentation liver/kidney issues topical treatmentb dermatophytomaa topical efinaconazole moderatea topical efinaconazole or oral terbinafine severea oral terbinafine +/ topical treatmentb f ir st -l in e t re a tm e n t (c o -t re a t ti n e a p e d is , a s n e e d e d , i n a ll p a ti e n ts ) patient characteristics these are topline recommendations for treatment. all patient characteristics—including age, disease duration/severity, clinical presentation, concomitant medications, and comorbidities—must be taken into consideration when making treatment decisions, particularly for patients with more complex presentation. for all treatments, check prescribing information for potential drug-drug interactions and contraindications. amild defined as <20% nail involvement; moderate defined as 20%–60% nail involvement, severe defined as >60% nail involvement and/or additional factors (ie, matrix involvement, 3 mm thickness great toenail, >1 great toenail involved, >3-4 toenails involved, total dystrophic nail); dermatophytoma8-10 is a specialized term used by some dermatologists and can be defined as onychomycosis presenting as yellow or white streaks/patches in subungual space. befinaconazole preferred due to higher rates of complete cure and mycologic cure versus other topical treatments. from lipner sr, et al. j drugs dermatol. 2021;20(10): doi:10.36849/jdd.6291. figure 3. therapeutic recommendations by drug +/− + treatment topical monotherapy topical + oral (terbina�ne or �uconazole) oral (+/topical) ideal for the following: • milda or moderatea disease (e�naconazole) • pediatric patients (e�naconazole) • treatment of dermatophytomasa (e�naconazole) • patients with liver/kidney issues • consider for maintenance therapy to prevent relapse (long-term, from once-weekly to once-daily) • moderatea or severea disease (terbina�ne) • fingernail with con�rmed candida albicans infection (�uconazole) • second-line for patients who fail terbina�ne (�uconazole) • patients aged ≥65 years • patients with diabetes • patients with peripheral vascular disease • immunocompromised patients • patients with certain concomitant medications (oral optional) • second-line for patients who fail topical monotherapy these are topline recommendations for treatment. all patient characteristics—including age, disease duration/severity, clinical presentation, concomitant medications, and comorbidities—must be taken into consideration when making treatment decisions, particularly for patients with more complex presentation. for all treatments, check prescribing information for potential drug-drug interactions and contraindications. efinaconazole preferred for topical treatment due to higher rates of complete cure and mycologic cure versus other topical treatments. asee figure 2 footnote for definitions. from lipner sr, et al. j drugs dermatol. 2021;20(10): doi:10.36849/jdd.6291. figure 4. patient education handout when to contact your doctor • if family/household members have athlete’s foot or nail infections, they should seek treatment and take precautions to prevent spread. • if you see signs of athlete’s foot or reinfection of the nail(s), contact your doctor as soon as possible.  • wear properly sized shoes with adequate toe boxes. avoid narrow-toed shoes or high heels. avoid non-breathable athletic shoes. • don’t walk barefoot in public facilities such as pools, spas, locker rooms, showers, or gyms. wear �ip �ops or shower shoes. • when trying on new shoes, always wear socks. • use antifungal spray or powder in your shoes and/or a uv shoe sanitizer everyday. • wear moisture-wicking socks or copper or silver antimicrobial socks. • alternate athletic shoes to allow each pair to dry thoroughly for 2–3 days between uses. • replace athletic shoes after 500 miles of use. • keep nails short and clean. • only visit a licensed manicurist/pedicurist; bring your own tools and clean them. • don’t pick your toenails or scratch your feet with �ngernails. • don’t use the same clippers/�les used on abnormal nails on normal nails. • don’t share personal nail care instruments, soap, or towels. • wash and dry your hands after contact with infected feet or nails. • dry feet thoroughly after washing. • wash towels, socks, and clothes after every use. socks and other contaminated clothing/towels should be washed at 140°f (60°c). what to know about fungal nail infections • nail fungus may be in your shoes, carpet, bathroom, locker rooms, etc. • toenails grow slowly, so improvements could take 1–2 years to be noticeable. • even after the fungus is gone, the affected nail(s) may never look completely normal. • once the fungus is cleared, it can return. use treatment(s) recommended by your doctor and follow the steps below to help prevent new infections: footwear personal care and laundry from lipner sr, et al. j drugs dermatol. 2021;20(10): doi:10.36849/jdd.6291. conclusions � these therapeutic recommendations, based on new clinical data, provide important updates to previous guidelines/consensus documents to assist healthcare practitioners in the diagnosis and treatment of toenail onychomycosis � onychomycosis should be assessed clinically and confirmed with microscopy, histology, and/or culture � terbinafine is the primary choice for oral treatment and efinaconazole 10% for topical � efinaconazole can be used for maintenance to prevent recurrence � for optimal outcomes, patients should be counseled regarding treatment expectations as well as follow-up care and maintenance post-treatment references 1. gupta ak, paquet m. j cutan med surg. 2015;19(3):260-273. 2. ghannoum ma, hajjeh ra, scher r, et al. j am acad dermatol. 2000;43(4):641-648. 3. rosen t, friedlander sf, kircik l, et al. j drugs dermatol. 2015;14(3):223-233. 4. gupta ak, stec n. f1000res. 2019;8. 5. tosti a, elewski be. skin appendage disord. 2016;2(1-2):83-87. 6. narasimha murthy s, wiskirchen de, bowers cp. j pharm sci. 2007;96(2):305-311. 7. ameen m, lear jt, madan v, et al. br j dermatol. 2014;171(5):937-958. 8. burkhart cn, burkhart cg, gupta ak. j am acad dermatol. 2002;47(4):629-631. 9. roberts dt, evans eg. br j dermatol. 1998;138(1):189-190. 10. wang c, cantrell w, canavan t, elewski b. skin appendage disord. 2019;5(5):304-308. author disclosures shari r. lipner has served a consultant for ortho dermatologics, hoth therapeutics, and verrica. warren s. joseph has served as consultant and speaker for ortho dermatologics. tracey c. vlahovic has served as investigator and speaker for ortho dermatologics. richard k. scher has nothing to disclose. phoebe rich has received research and educational grants from abbvie, allergan, anacor pharmaceuticals, boehringer ingelheim, cassiopea, dermira, eli lilly, galderma, janssen ortho inc., kadmon corporation, leo pharma, merck, moberg derma, novartis, pfizer, ranbaxy laboratories limited, sandoz, viamet pharmaceutical inc., innovation pharmaceuticals (cellceutix), and cutanea life sciences. mahmoud ghannoum has acted as a consultant or received contracts from scynexis, inc, bausch & lomb, pfizer, and mycovia. c. ralph daniel has provided clinical research support to ortho dermatologics and owns stock in medimetriks pharmaceuticals. boni elewski has provided clinical research support (research funding to university) for abbvie, anaptys-bio, boehringer ingelheim, bristol-myers squibb, celgene, incyte, leo pharma, lilly, merck, menlo, novartis, pfizer, regeneron, sun pharma, ortho dermatologics, vanda; and as consultant (received honorarium) from boehringer ingelheim, bristol meyers squibb, celgene, leo pharma, lilly, menlo, novartis, pfizer, sun pharma, ortho dermatologics, verrica. patient education � it is important to manage patient expectations when treating onychomycosis: optimal results can take over a year and clinical cure/normal nail appearance may not be possible � patients should also be educated on the high recurrence rates (6.5%–53%)5; as such, regular follow-up visits with patients are recommended (3–6 months after oral or 1 year after topical treatment) � a physical handout (figure 4) should also be provided to patients, explaining follow-up care/maintenance and highlighting that long-term treatment is more than just pharmacologic (eg, personal care, footwear selection/care, laundry) skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 52 brief article erythema multiforme is not always erythema multiforme hana nasim ahmed, md1, meagan mandabach olivet, ba1, carly elston, md1 boni elewski md1 1the university of alabama at birmingham rowell syndrome (rs) describes the rare presentation of em like lesions found in association with a diagnosis of lupus erythematosus (le). major diagnostic criteria includes le, em, and anti-nuclear antibodies. minor criteria includes: chilblains, anti-ro/anti-la antibodies, and rheumatoid factor. we present a 26-year-old white male seen in consultation for chronic erythema multiforme (em) with a duration of 6 months unresponsive to treatment. prior to being seen in our clinic, he had been evaluated by another dermatologist and was diagnosed with biopsy-proven em. in the following weeks, he received prednisone tapers, topical corticosteroids, oral antihistamines, valacyclovir, azithromycin, and topical antifungals, to which his rash did not respond. preliminary lab work was also ordered, including a complete blood count (cbc), a comprehensive metabolic panel (cmp), and an antinuclear antibody (ana). the ana was positive, and he was pending a consult with rheumatology. upon evaluation, he was nearly erythrodermic. on obtaining further history, the patient denied recent new medications, pneumonia or upper respiratory infection, herpes labialis, or genital herpes. on examination, the rash consisted of pink annular-to-polycyclic plaques with dusky centers and thin powdery scale that coalesced, mainly localized to his torso, back, and proximal upper and lower extremities with 60-70% abstract rowell syndrome (rs) describes the rare presentation of em like lesions found in association with a diagnosis of lupus erythematosus (le). major diagnostic criteria includes: le, em, and anti-nuclear antibodies. minor criteria includes: chilblains, anti-ro/anti-la antibodies, and rheumatoid factor. we present a 26-year-old white male seen in consultation for chronic erythema multiforme (em) with a duration of 6 months unresponsive to treatment. prior to our evaluation, he had been seen by another dermatologist and was diagnosed with biopsy-proven em. his rash did not respond to previous treatments, including corticosteroids and antifungals. lab results showed a positive ana and positive anti-ro antibody. the patient met diagnostic criteria for rs and was started on hydroxychloroquine 200 mg twice daily. improvement was noticed two weeks after beginning treatment. our case demonstrates that an atypical presentation of recurrent erythema multiforme, which does not respond to typical em treatment, should raise a suspicion for rs and prompt screening for autoimmune markers and lupus erythematosus. introduction case report skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 53 bsa involvement. his palms, soles, and mucous membranes were spared (figure 1). figure 1 additional lab work was obtained and included cbc, cmp, glucose-6-phosphate dehydrogenase, t-spot test, acute hepatitis panel, flow cytometry, a dermatomyositis panel, ana, anti-ro, and anti-la. the labs were within normal limits except for a repeated positive ana (1:320 with a speckled pattern) and positive anti-ro antibody. punch biopsies were collected from three distinct anatomical locations, two were sent for hematoxylin and eosin (h&e) staining and the other for direct immunofluorescence (dif). the dif was negative and h&e staining indicated an interface dermatitis with prominent dyskeratotic cells appreciated at multiple levels of the epidermis, favoring an em spectrum disorder (figures 2 and 3). there was also increased mucin noted in the dermis. a deep inflammatory infiltrate involving adnexal structures was not appreciated. given the positive ana and anti-ro, a diagnosis favoring rowell syndrome (rs) was made and the patient was started on hydroxychloroquine 200 mg twice daily. after two weeks after initiation of this treatment, the patient began to note improvement of his rash. figure 2 figure 3 skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 54 rs describes the rare presentation of em like lesions found in association with a diagnosis of lupus erythematosus (le). first described in the literature by scholtz in 1922, the diagnostic criteria of le, em-like lesions, and positive rheumatoid factor and antinuclear antibodies was created by rowell et al. in 1963. zeitouni et al. proposed the major criteria of le, em, and anti-nuclear antibodies, and the minor criteria of chilblains, anti-ro/anti-la antibodies, and rheumatoid factor. our patient meets two of the major diagnostic criteria and fulfills the minor criterion of antiro and anti-la antibodies. the majority of reports discuss adult female patients, making this report unique with an adult male patient.1 it is important to note that subacute cutaneous lupus erythematosus (scle) can also appear as annular pink plaques on the trunk; however, upon examination on dif, scle tends to show a granular deposition of igg and igm at the dermo-epidermal junction and sometimes within the epidermis. in general, though, a negative dif does not necessarily rule out a diagnosis of cutaneous lupus. in our case, the dif was negative and h&e staining indicated an interface dermatitis with prominent dyskeratotic cells appreciated at multiple levels of the epidermis, favoring an em spectrum disorder. a thickened basement membrane zone or deep inflammatory infiltrate involving adnexal structures was not appreciated. given the clinical and histological features, the rash was diagnosed as em rather than scle. rs is typically associated with acute cutaneous lupus erythematosus (acle).2 as noted in our case, a primary diagnosis of le was not met. though le is a major diagnostic criterion of rs, another case report by arevalo et al. documented a case of a 20 year-old male with no prior le diagnosis.3 clinicians evaluating an atypical presentation of em should keep rs in mind regardless of a previous diagnosis of le, refer their patients for the screening of le, and order appropriate serology. rs has been characterized by its absence of triggering factors, as in this case, distinguishing it from em and le.4,5 because of this, a thorough history ruling out all known causes of em, such as herpes simplex or drug-induced, is imperative for a diagnosis of rs. additionally, because of the use of immunosuppressant drugs, le patients may be predisposed to infections which also can trigger em.4 brӑnişteanu et al. outlined a rare case in which rs occurred one week after beginning treatment for helicobacter pylori.6 in a report by ward et al., a patient’s rs was attributed to sun exposure following a tapered dose of hydroxychloroquine and methotrexate, though photosensitivity is also characteristic of le. 7 management for rs includes the use of steroids and immunosuppressive drugs, including azathioprine and cyclosporine.3,4,7 antimalarials, such as hydroxychloroquine and chloroquine, have also been employed, as well as dapsone.1, 4, 8, 9 our patient has responded well to hydroxychloroquine. rs is a rare and complex diagnosis requiring a thorough history and screening. as our case demonstrates, an atypical presentation of recurrent erythema multiforme which does not respond to typical em treatment should raise a suspicion for discussion conclusion skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 55 rs and prompt screening for autoimmune markers and lupus erythematosus. conflict of interest disclosures: none funding: none corresponding author: meagan mandabach olivet, b.a. the university of alabama at birmingham email: mkmandab@uab.edu references: 1. gallo l, megna m, festa b, et al. rowell syndrome: a diagnostic challenge. j clin aesthet dermatol. apr 2020;13(4):40-42. 2. okon lg, werth vp. cutaneous lupus erythematosus: diagnosis and treatment. best pract res clin rheumatol. jun 2013;27(3):391-404. doi:10.1016/j.berh.2013.07.008 3. arevalo ab, nassar r, krishan s, lakshmanan p, salgado m, chokshi p. lupus never fails to deceive us: a case of rowell's syndrome. case rep rheumatol. 2020;2020:8884230. doi:10.1155/2020/8884230 4. anuj sharma rs. rowell syndrome: a case report and review of literature`. internet journal of rheumatology and clinical immunology. 1 september 2016 2016;4(1) 5. devang solanki ed, nishita drji. case report of a rowell’s syndrome. international journal of science and research. 2014;3(1):7-8. 6. branisteanu de, ianosi sl, dimitriu a, stoleriu g, oanta a, branisteanu dc. druginduced rowell syndrome, a rare and difficult to manage disease: a case report. exp ther med. jan 2018;15(1):785-788. doi:10.3892/etm.2017.5557 7. callen jp, klein j. subacute cutaneous lupus erythematosus. clinical, serologic, immunogenetic, and therapeutic considerations in seventy-two patients. arthritis rheum. aug 1988;31(8):1007-13. doi:10.1002/art.1780310811 8. muller cs, hinterberger lr, vogt t. successful treatment of rowell syndrome using oral cyclosporine a. int j dermatol. aug 2011;50(8):1020-2. doi:10.1111/j.13654632.2010.04848.x 9. lee a, batra p, furer v, cheung w, wang n, franks a, jr. rowell syndrome (systemic lupus erythematosus + erythema multiforme). dermatol online j. aug 15 2009;15(8):1. 10. zeitouni nc, funaro d, cloutier ra, gagne e, claveau j. redefining rowell's syndrome. br j dermatol. feb 2000;142(2):343-6. doi:10.1046/j.1365-2133.2000.03306.x 11. bolognia jl, schaffer jv, cerroni l, callen jp. chapter 41 lupus erythematosus. in: dermatology. edinburgh: elsevier; 2018. mailto:mkmandab@uab.edu 404 not found methods • human donor skin tissue samples of 500-µm thickness were pretreated with a low-power 1440-nm diode laser, 1927-nm diode laser, or received no pretreatment prior to application of eye serum (table) table. experimental parameters for uptake analysis • eye serum was applied to laser-treated skin and untreated controls, and permeation was measured up to 24 hours after application (figure 1) • samples were filtered and analyzed using high-performance liquid chromatography to measure cumulative permeation and retention • total uptake was calculated as the sum of the normalized cumulative permeation and retention in each sample figure 1. study design for testing uptake of topicals on skin tissue. pbs, phosphate-buffered saline. results uptake • pretreatment with the 1440-nm laser increased uptake of mineral eye serum at 24 hours posttreatment by almost 2 times compared to untreated controls (47.1 vs 23.7 mg/cm2) • pretreatment with the 1927-nm laser with lower power and energy settings (0.6 w, 4.5 mj) enhanced uptake of mineral eye serum by ~1.6 times compared to untreated controls (39.0 vs 23.7 mg/cm2) • higher power and energy settings (1 w, 7.5 mj) with the 1927-nm laser enhanced uptake of eye serum by ~2.7 times compared to untreated controls (63.6 vs 23.7 mg/cm2) permeation • permeation was increased by >2 times with 1440-nm laser pretreatment compared to untreated controls (39.7 vs 19.4 mg/cm2; figure 2) • low-power 1927-nm pretreatment (0.6 w) increased permeation by 1.5 times compared to untreated controls (29.4 vs 19.4 mg/cm2) • higher-power 1927-nm pretreatment (1 w) increased permeation by almost 3 times compared to untreated controls (57.6 vs 19.4 mg/cm2) • laser-treated samples showed enhanced uptake within 15 minutes of application, whereas untreated controls did not demonstrate permeation until 2 hours figure 2. cumulative permeation of mineral eye serum after laser pretreatment. values are mean ± standard deviation. synopsis • the stratum corneum limits transdermal uptake of topical therapies, potentially reducing their clinical efficacy1 • non-ablative fractional laser pretreatment enhances topical delivery and absorption, reduces thermal side effects, and creates microscopic treatment zones (mtz) that spare the stratum corneum2-4 • clinical practice may be improved by understanding the relationship between topical uptake and energy-device settings, such as wavelength, peak power, and spot density quantifying uptake of eye serum after 1440-nm or 1927-nm non-ablative fractional diode laser treatment jordan v. wang, md, mbe, mba1; paul m. friedman, md1,2; adarsh konda, pharmd3; catherine parker, np, msn4; roy g. geronemus, md1 1laser & skin surgery center of new york, new york, ny; 2dermatology and laser surgery center, houston, tx; 3bausch health us, llc, bridgewater, nj; 4solta medical, bothell, wa objective • to quantify uptake of an eye serum, obagi® elastiderm (long beach, ca; 2010 formulation), using donor skin tissue pretreated with a 1440-nm or 1927-nm non-ablative fractional diode laser (320 mtz/cm2; clear + brilliant® laser system; solta medical, bothell, wa) conclusions • in this ex vivo analysis, pretreatment with low-power 1440-nm or 1927-nm non-ablative fractional diode lasers not only increased overall uptake of mineral eye serum but also achieved more rapid absorption after application compared to untreated controls • pretreatment with the 1927-nm wavelength at low power (0.6 w) showed similar uptake enhancement to 1440-nm laser pretreatment at 3 w relative to untreated control (~1.6 vs 2 times) • 1927-nm pretreatment at 1 w enhanced uptake of mineral eye serum by ~2.7 times relative to untreated control • these results provide a foundation for guidance on the use of non-ablative lasers in clinical studies on topical uptake enhancement presented at the 2021 fall clinical dermatology conference • october 21-24, 2021 • las vegas, nv, and virtual funding information: this study was sponsored by solta medical. medical writing support was provided by medthink scicom and funded by solta medical. disclosures: jvw is an investigator for solta medical. pmf serves on the advisory board and speaker bureau for solta medical. ak and cp are employees of and may hold stock or stock options in solta medical. rgg is an investigator and advisory board member for solta medical. references: 1. lee et al. eur j pharm sci. 2016;92:1-10. 2. machado et al. aesthetic plast surg. 2021;45:1020-1032. 3. friedman et al. j drugs dermatol. 2020;19:s3-s11. 4. farkas et al. aesthet surg j. 2013;33:1059-1064. figure 1 sample & refill 500-µm skin graft topical formulation pbs solution w/ 0.2% sodium azide donor chamber permeation/diffusion chamber stir bar stir rotation parameter setting device wavelength, nm 1440 1927 1927 spot density, mtz/cm2 320 320 320 peak power, w 3 0.6 1 spot size, µm 130 130 130 pulse energy, mj 9 4.5 7.5 mtz, microscopic treatment zones. figure 2 0 10 20 30 40 50 60 70 0 5 10 15 20 25 30 time, hours control 1435nm-1.2w-9mj 1927nm-0.6w-4.5mj 1927nm-1.0w-7.5mj control 1440 nm/3 w/9 mj 1927 nm/0.6 w/4.5 mj 1927 nm/1 w/7.5 mj 29.40 57.65 39.77 19.37 c um ul at iv e pe rm ea ti o n, m g/ cm 2 skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 319 short communications treatment of refractory pruritus with dupilumab in a patient with dermatomyositis nathan l. bowers, md, phd1 and william w. huang md, mph1 1department of dermatology, wake forest school of medicine, winston-salem, nc dermatomyositis (dm) is an idiopathic inflammatory myopathy characterized by progressive muscle weakness and pathognomonic skin findings. cutaneous disease in dm is often refractory to treatment and can become the most challenging component to manage effectively. herein, we present a case of a patient with dm who had recalcitrant cutaneous disease treated with dupilumab with remarkable response. a 54-year-old woman presented with several month history of fatigue, extremity weakness, and pruritic rash. her exam was significant for violaceous periorbital erythema and poikilodermatous erythema of the anterior neck, upper back, bilateral arms, and lateral thighs (fig1). a skin biopsy was obtained demonstrating a vacuolar interface dermatitis. creatinine kinase and aldolase were within normal range. given clinical signs of myopathy, a mri was ordered and demonstrated myositis. myomarker panel was significant for mda-5 (p140/cadm140) antibody positivity. the patient was also diagnosed with interstitial lung disease (ild) based on chest computed tomography (ct) results. given her concurrent ild she was started on mycophenolate mofetil and titrated up to 1500 mg bid as well as prednisone 1 mg/kg. she was transiently on hydroxychloroquine, but discontinued due to lack of efficacy. despite optimized medical therapy, she continued to have significant muscle weakness as well as cutaneous involvement. given the recalcitrant nature of her disease she was started on rituximab 1000 mg with protocol of two infusions separated by two weeks. she had subjective and objective improvement in her muscle weakness; however, she endorsed persistent skin flaring with significant pruritus. to address her recalcitrant cutaneous disease, she was started on dupilumab with a loading dose of 600 mg and two-week maintenance doses of 300 mg. importantly, at time of initiating dupilumab patient was on stable dose of mycophenolate mofetil 1500 mg bid and stable dose of prednisone 10 mg for several months and her most recent rituximab infusion was two months prior to first dose of dupilumab. at two-week follow-up she endorsed complete resolution of her pruritus and improvement in her skin. at six-week follow-up, she demonstrated no erythema on exam with only post-inflammatory hyperpigmentation (fig1). she tolerated dupilumab with no adverse side effects. dupilumab is an interleukin (il)-4-receptor monoclonal antibody inhibiting signaling of il-4 and il-13, key drivers of type 2-driven inflammation (th2). interestingly, a recent study demonstrated significantly elevated skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 320 figure 1. (a) poikilodermatous erythematous plaques on back and lateral leg prior to treatment with dupilumab. (b) after six weeks of treatment with dupilumab background erythema is minimal to absent with only postinflammatory hyperpigmentation. muscle tissue il-4 levels in patients with dm1, prior to this ishii et al, found that th2 cells predominate in peripheral blood of active dm, and that a decreased intracellular ifn-γ/il-4 ration in cd4+ cells may be a useful as a marker of disease activity.2 in addition to inhibiting signaling of il-4, a key driver of th2 mediated inflammation, dupilumab also demonstrates the ability to reduce expression of il-31.3 a recent study highlighted the role of il-31 in dm, demonstrating increase gene expression of il-31 and il-31ra in lesional skin compared to non-lesional skin and healthy controls.4 collectively, this suggest a possible mechanism of action of dupilimab through its direct effect on th2 mediated inflammation in dm as well as an indirect effect on the expression of il-31, a proposed driver of pruritus in dm. this case highlights the use of dupilumab as a novel therapy in the treatment of cutaneous manifestations of dm. additional studies are needed to better assess efficacy and safety profile. conflict of interest disclosures: none funding: none corresponding author: nathan l. bowers, md, phd department of dermatology wake forest school of medicine. medical center boulevard winston-salem, nc 27157-1071 phone: 336-716-7740 fax: 336-716-7732 e-mail: nbower@wakehealth.edu references: 1. giris m, durmus h, yetimler b, tasli h, parman y, tuzun e. elevated il-4 and ifn-gamma levels in muscle tissue of patients with dermatomyositis. in vivo. jul-aug 2017;31(4):657-660. doi:10.21873/invivo.11108 2. ishii w, matsuda m, shimojima y, itoh s, sumida t, ikeda s. flow cytometric analysis of a. b. skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 321 lymphocyte subpopulations and th1/th2 balance in patients with polymyositis and dermatomyositis. intern med. 2008;47(18):15939. doi:10.2169/internalmedicine.47.0967 3. guttman-yassky e, bissonnette r, ungar b, et al. dupilumab progressively improves systemic and cutaneous abnormalities in patients with atopic dermatitis. j allergy clin immunol. jan 2019;143(1):155-172. doi:10.1016/j.jaci.2018.08.022 4. kim hj, zeidi m, bonciani d, et al. itch in dermatomyositis: the role of increased skin interleukin-31. br j dermatol. sep 2018;179(3):669-678. doi:10.1111/bjd.16498 skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 402 resident competition research articles erythema multiforme major caused by topical imiquimod alexandra edelman md,1 j. mark jackson md,1 alfred knable md1 1division of dermatology, university of louisville, louisville, ky erythema multiforme (em) is an acute, selflimited inflammatory skin disease that is associated with an immune reaction to various triggers, such as herpes simplex virus, mycoplasma pneumoniae, and medications. commonly implicated drugs include nonsteroidal anti-inflammatories, allopurinol, phenobarbital, phenytoin, and sulfonamides.1 topically applied medications are a rare cause of em or em-like eruptions.1 we report one patient with em major from imiquimod 5% topical cream. a 65 year-old male with no significant past medical history presented with a biopsy proven squamous cell carcinoma in-situ on his right upper arm (figure 1a). he was instructed to apply imiquimod 5% topical cream to the area for five days using a oncedaily monday to friday regimen for a total of six weeks. he had never applied imiquimod before and was not on any other prescription or over the counter medications. there was no past history of hsv, and no viral or bacterial processes prior to the eruption. two weeks after beginning the imiquimod, he developed erythema, crusting, and scabbing on the right upper arm. at the same time, the patient developed painful erosions in his mouth. the following day he developed a rash on his palms that continued to worsen and spread up his arms over the next three days. he discontinued imiquimod at this time as recommended by his dermatologist. the rash continued to progress with worsening stomatitis and the patient was subsequently admitted to the hospital. physical exam revealed dusky targetoid lesions on his palms (figure 2a), erythematous papules on his arms, and crusted plaques and erosions on his buccal mucosa, lips and hard palate (figure 2b). there was marked crusting, erythema and tenderness at the site of imiquimod application on his right upper arm (figure 1b) and also in areas of actinic damage at other sites such as his nose and cheeks where he had not applied the imiquimod. genital and ocular mucosae were not affected. other potential causes of erythema multiforme were ruled out as the patient denied the use of any new medications other than imiquimod, denied any recent illnesses or a history of hsv infection. hsv swab was negative in the hospital. with the combination of oral steroids, supportive care and topical steroids, the rash resolved over the next three weeks. introduction case report skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 403 figure 1. squamous cell carcinoma in situ on right upper arm of patient (a) before biopsy and (b) two weeks after imiquimod treatment, coinciding with onset of erythema multiforme. (a) (b) figure 2. stomatitis (a) and targetoid lesions on the palms (b). (a) (b) skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 404 imiquimod 5% cream is a toll-like receptor (tlr)-agonist approved for the treatment of actinic keratosis, squamous cell carcinoma in-situ, basal cell carcinomas, and genital warts. the most common side effects of imiquimod include localized erythema, tenderness, scabbing, ulceration and occasionally flu-like symptoms.3 after reviewing the relevant literature, we found eight cases of erythema multiforme induced by topical imiquimod.3-8 of the eight cases of imiquimod-induced em, seven patients had a significant local reaction that subsequently led to the more distant cutaneous manifestations of erythema multiforme.3-8 the pathogenesis of imiquimod-induced em is not completely understood. imiquimod acts on both the innate and acquired immune system by activating toll-like receptor 7 leading to the secretion of proinflammatory cytokines, particular tumor necrosis factor, interferon, il 6 and 8, which in turn stimulates t-helper lymphocytes.1-2 this tlr activation cascade leading to a systemic release of cytokines is a potential mechanism of druginduced em. 2 it is also speculated that topical imiquimod produces systemic absorption, triggering a type iii or iv hypersensitivity reaction leading to erythema mutliforme.4 in conclusion, we present a case of topical imiquimod-induced em. imiquimod is a commonly used topical treatment for a variety of dermatologic conditions and clinicians must be aware of this rare but serious complication. furthermore, patients with an exuberant local reaction to imiquimod may be at higher risk of developing em. conflict of interest disclosures: none funding: none corresponding author: alexandra edelman, md division of dermatology, university of louisville 301 axis drive, apt 401 louisville, ky 40206 tel: (858) 692-6264 email: abbars02@louisville.edu references: 1. lerch m, mainetti c, beretta-piccoli bt, harr t. current perspectives on erythema multiforme. clinical rev allerg immunol. 2018;54:177-184. 2. hanna e, abadi r, abbas o. imiquimod in dermatology: an overview. int j dermatol. 2016; 55(8):831-44. 3. yanes da, kaffenberger ja, carr dr. erythema multiforme as a reaction to imiquimod 5% cream. dermatol online j. 2017; 23(2):18. 4. pena-lopez s, suarez-magdalena o, monteagudo b, cabanillas m. erythema multiforme cause by treatment with topical imiquimod 5% in a patient with gorlin syndrome. actas dermosifiliogr. 2018;109:278-281. 5. chan m, kennedy j, oakley a. erythema multiforme triggered by imiquimod 5% cream. australas j dermatol 2017;58(4):e257-258. 6. ballester i, guijarro j, niveiro m. erythema multiforme induced by imiquimod 5% cream. int j dermatol. 2014;53:e347-66. 7. garcia-arpa m, rodriguez-vazquez m, delgado portela m, vera iglesias e. erythema multiforme due to imiquimod 5% cream. actas dermosifliogr. 2010; 101:551-71. 8. christou e, morrow c. erythema multiforme to topical imiquimod 5% cream. australas j dermatol. 2012;53:32. discussion mailto:abbars02@louisville.edu synopsis • brodalumab is a fully human interleukin-17 receptor a antagonist approved for the treatment of moderate-to-severe plaque psoriasis in adult patients with inadequate response or loss of response to other systemic therapies1 methods • in amagine-2/-3 (nct01708603 and nct01708629), after a 12-week induction phase, patients received maintenance treatment as follows: brodalumab-treated patients were rerandomized to brodalumab 210 mg every 2 weeks (q2w); ustekinumab-treated patients continued to receive ustekinumab; and patients receiving placebo switched to brodalumab 210 mg q2w2 • at week 16, patients with inadequate response to ustekinumab (single static physician’s global assessment [spga] of ≥3 or persistent spga of 2 over ≥4 weeks) were eligible for rescue with brodalumab 210 mg q2w. after week 16, patients on ustekinumab with an inadequate response remained on ustekinumab • efficacy was assessed by psoriasis area and severity index 75%, 90%, and 100% response rates (pasi 75, 90, and 100) for patients who were rescued with 36 weeks of brodalumab 210 mg q2w after an inadequate response to ustekinumab at week 16 (n=124) and for patients who continued on ustekinumab after an inadequate response to ustekinumab after week 16 (n=149), stratified by tumor necrosis factor α (tnfα) inhibitor treatment before entering the study (no prior tnfα inhibitor experience, prior tnfα inhibitor nonfailure, or prior tnfα inhibitor failure) results • at week 52, after 36 weeks of retreatment, pasi 75, pasi 90, and pasi 100 response rates were 72.6%, 58.1%, and 36.3% for patients rescued with brodalumab and 61.7%, 25.5%, and 5.4% for patients who continued ustekinumab, respectively (figure 1) figure 1. pasi rates in patients with inadequate responsea to ustekinumab rescued with brodalumab at week 16 or continuing on ustekinumab after week 16. pasi 75, 90, and 100, psoriasis area and severity index 75%, 90%, and 100% improvement; q2w, every 2 weeks; spga, static physician’s global assessment. ainadequate response was defined as a single spga score ≥3 or persistent spga score of 2 over ≥4 weeks. • at week 52, patients who were rescued with brodalumab demonstrated higher pasi 75, pasi 90, and pasi 100 response rates than those who continued ustekinumab, regardless of prior tnfα inhibitor treatment (figure 2) figure 2. pasi rates at week 52 in patients with inadequate response to ustekinumab rescued with brodalumab 210 mg q2w at week 16 or continuing on ustekinumab after week 16, analyzed by previous tnfα inhibitor experience. observed analysis. n1, number of patients who had a valid measurement at week 52; pasi 75, 90, and 100, psoriasis area and severity index 75%, 90%, and 100% improvement; q2w, every 2 weeks; tnfα, tumor necrosis factor α. efficacy of brodalumab vs ustekinumab by prior tnfα inhibitor exposure: post hoc analysis of two phase 3 psoriasis studies alan menter,1 erin boh,2 george michael lewitt,3 abby jacobson4 1baylor university medical center, dallas, tx; 2tulane university school of medicine, new orleans, la; 3illinois dermatology institute, chicago, il; 4ortho dermatologics (a division of bausch health us, llc), bridgewater, nj objective • to evaluate the efficacy of brodalumab vs ustekinumab (an anti–interleukin-12/-23 monoclonal antibody) in individuals who were rescued with brodalumab or continued ustekinumab, stratified by prior treatment with tumor necrosis factor α (tnfα) inhibitors, in a post hoc analysis of two phase 3 studies (amagine-2/-3) conclusions • patients with psoriasis who were rescued with 36 weeks of retreatment with brodalumab demonstrated higher response rates than those who continued ustekinumab, regardless of prior tnfα inhibitor treatment • brodalumab may be a safe and effective treatment after inadequate response to previous biologics funding: this study was sponsored by ortho dermatologics. medical writing support was provided by medthink scicom and funded by ortho dermatologics. ortho dermatologics is a division of bausch health us, llc. author disclosures: am reports receiving compensation from or serving as an investigator, consultant, advisory board member, or speaker for abbvie, allergan, amgen, anacor pharmaceuticals, boehringer ingelheim, celgene corporation, dermira, eli lilly, galderma, janssen biotech, leo pharma, merck & co., neothetics, novartis ag, pfizer, regeneron, symbio/maruho, vitae, and xenoport. eb reports serving as an investigator/member of a speakers bureau for and/or receiving grants from abbvie, actelion, celgene, elorac, incyte, janssen, novartis, ortho dermatologics, pfizer, regeneron, soligenix, sun pharmaceutical, and ucb; except for sun pharmaceutical, investigation and grant support payments were made to the tulane university school of medicine. gml reports partnership/ownership with illinois dermatology institute (the chicago loop) and reports receiving grants/research support from and/or serving on a speakers bureau for abbvie, aobiome, galderma, janssen, lilly, novartis, ortho dermatologics, sol-gel, and ucb. aj is an employee of ortho dermatologics (a division of bausch health us, llc). previous presentation information: data included in this poster have been previously presented in part at the 76th annual meeting of the american academy of dermatology; february 16-20, 2018; san diego, ca; and maui derm for dermatologists; january 25-29, 2020; maui, hi. references: 1. siliq [package insert]. bausch health us, llc; 2017. 2. lebwohl et al. n engl j med. 2015;373:1318-1328. presented at fall clinical dermatology conference • october 21-24, 2021 • las vegas, nv sponsored by ortho dermatologics, a division of bausch health us, llc. 16 32 52 16 32 52 16 32 52 0 20 40 60 80 100 re sp on de rs , % study week pasi 100 0 20 40 60 80 100 re sp on de rs , % study week pasi 90 0 20 40 60 80 100 re sp on de rs , % study week pasi 75 rescued with brodalumab 210 mg q2w after inadequate response to ustekinumab at week 16 (n=124); 36 weeks of brodalumab therapy continued on ustekinumab after inadequate response after week 16 (n=149); 52 weeks of continuous ustekinumab 72.6 61.7 58.1 25.5 36.3 5.4 70.9 71.4 50.0 33.7 25.0 13.3 0 20 40 60 80 100 no prior tnf tnf nonfailure tnf failure re sp on de rs , % pasi 90 88.6 92.9 58.3 75.3 70.8 53.3 0 20 40 60 80 100 no prior tnf tnf nonfailure tnf failure re sp on de rs , % pasi 75 responded to prior tnfα inhibitor treatment no prior tnfα inhibitor experience no prior tnfα inhibitor experience failed prior tnfα inhibitor treatment n1= 79 1289 1514 24 responded to prior tnfα inhibitor treatment failed prior tnfα inhibitor treatment 45.6 42.9 25.0 7.9 4.2 0 0 20 40 60 80 100 no prior tnf tnf nonfailure tnf failure re sp on de rs , % pasi 100 no prior tnfα inhibitor experience responded to prior tnfα inhibitor treatment failed prior tnfα inhibitor treatment rescued with brodalumab 210 mg q2w after inadequate response to ustekinumab at week 16; 36 weeks of brodalumab therapy continued on ustekinumab after inadequate response after week 16; 52 weeks of continuous ustekinumab skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 474 in-depth review an investigation of makeup ingredients and their effects on acne cosmetica with dermatologic practice recommendations hira ghani, ba1, raphia k. rahman ba, mbs2, kevin liu, do3, stefani cubelli, do4 1 new york institute of technology college of osteopathic medicine, old westbury, ny 2 rowan school of osteopathic medicine, rowan, nj 3 lehigh valley dermatology, allentown, pa 4 st. john’s episcopal hospital, far rockaway, ny acne vulgaris is the most common skin disease affecting late adolescents across the globe. according to a global burden of disease study, approximately 85% of young adults between the ages of 12-25 are afflicted by acne vulgaris. its prevalence has also continued to increase over time in the us as well as other western countries including france and the united kingdom.1 the prevalence of adolescent acne has been reported to range between 81 to 95 percent in males and 79 to 82 percent in females.2 the annual treatment cost of acne is approximately $3 billion.3 given the rise of acne diagnosis not only in teenagers but also across multiple nationalities and races, it is important for clinicians to understand the basic pathogenesis, and most importantly, investigate new exacerbating factors that may not have been previously associated with acne epidemiology. acne is a chronic inflammatory skin disorder of the sebaceous glands of the hair follicle. it is caused by a cascade of different factors, subsequently leading to the formation of a microcomedone, and eventually acne abstract acne cosmetica, a type of acne linked to cosmetic usage, is characterized by persistent mild breakouts and occurs due to the interplay between sebum and trapped comedogenic products in makeup products. regular cosmetic usage may cause acne since it has been determined that a reduction in makeup application can help reduce its severity. there is a pressing need for dermatologists and patients to select appropriate, well-tolerated, and non-comedogenic makeup products containing active ingredients that help to eradicate acne. this literature review will thus examine common ingredients found in makeup products that act as comedogenic irritants, acnefriendly ingredients, and explore dermatologic recommendations to address beauty product use in acne-prone patients. both pubmed and google scholar were searched using keywords skincare and makeup ingredients combined with acne cosmetica in adolescents and dermatology. this literature review has indicated that patients suffering from acne should be recommended to avoid using comedogenic products and switch to acne-friendly ingredients that are safe for skin. dermatologists should recommend the use of prescription topical medications containing ingredients such as retinol and salicylic acid to yield visible and noticeable results. these findings help to strengthen the dermatologists' understanding of common active ingredients found in beauty products and helps guide recommendations for patients suffering from acne. introduction skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 475 vulgaris.4 the most common cause of acne vulgaris is an increase of sebum production and secretion, or a change in sebum components, which results in the clogging of pores.4 excessive sebum production is caused by the enlargement of sebaceous glands due increasing levels of dhea-s during the prepubertal period. this makes the skin appear shiny and eventually leads to the formation of a hardened plug or comedone.5 acne can also be triggered by a change in sebum composition. acne is specifically triggered when there is an imbalance between the ratio of monounsaturated fatty acids to total fatty acids. the ratio of triglycerides and wax esters is notably higher in the sebum of individuals with acne.4 acne vulgaris can further be subdivided into non-inflammatory and inflammatory acne. non-inflammatory acne is composed of whiteheads (open comedones) and blackheads (closed comedones) while inflammatory acne is associated with painful red cysts that often cause scarring over time. hormonal imbalance triggers the excessive production of sebum, which when combined with dead skin cells, promotes the development of both inflammatory and noninflammatory acne.2 propionibacterium acnes, a skin-colonizing bacteria, is highly responsible for inducing inflammatory acne by increasing sebum secretion and leading to a mounted immune response via increased expression of pro-inflammatory mediators such as il-1 alpha, il-2, and most importantly, tlr-2.6 moreover, a high glycemic index of diet may also participate in the pathogenesis of both inflammatory and non-inflammatory types of acne vulgaris. diets based on products with a high glycemic index leads to hyperinsulinemia, thus stimulating the secretion of androgens and causing an increased production of sebum by elevating the level of insulin-like growth factor 1 (igf1).7 igf-1 influences comedogenic factors such as androgens, growth hormone and glucocorticoids.7 these comedogenic factors increase the endogenous levels of igf-1 in blood, which further increases levels of androgens, thereby creating a vicious cycle of excessive production of sebum.7 in today's world, popular retail stores such as sephora® and ulta beauty® have lured customers into purchasing various high end and luxurious makeup products; the 2019 revenue of the cosmetic and beauty industry in the u.s. was approximately 49.2 billion dollars alone.8 however, these products may often contain ingredients that are potentially harmful to the skin, especially if the consumer has acne-prone or sensitive skin. acne cosmetica is a form of acne linked to cosmetic usage, characterized by persistent mild breakouts resulting from the complex interplay between sebum and trapped comedogenic products in makeup.9 while makeup can damage the skin if used aggressively and routinely, noncomedogenic makeup applied with caution and in moderate amounts may conceal scars and blemishes, helping to increase the self-esteem of adolescents struggling with acne.10 the purpose of this literature review is to examine ingredients found in makeup products that can act as irritants and as an agent of camouflage for acne. furthermore, this literature review will investigate whether makeup is recommended for use on acneprone skin, review acne-friendly ingredients found in products, and propose recommendations on how dermatologists should counsel acne-prone patients in regards to product choices for makeup application. skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 476 we searched pubmed and google scholar using search terms skincare and makeup ingredients combined with acne cosmetica in adolescents and dermatology. we limited our search to articles available in english and those published between 1972 and 2020. acne and cosmetics for many years, it has been speculated that cosmetic products are implicated in the pathogenesis of acne vulgaris. acne cosmetica, as the name suggests, is one such form of acne linked to cosmetic usage. the complex interplay between sebum and trapped comedogenic products in makeup cause the eruption of acne cosmetica, which is characterized by persistent mild breakouts, comprising comedones along the forehead, cheeks, neck and scalp.9 occasionally, papules and pustules may also be seen in acne cosmetica, but they are far less common.9 however, this association was difficult to prove as both the incidence of acne vulgaris and the use of cosmetics have steadily increased over time. recently, there have been an increasing amount of studies linking cosmetic usage to the development of acne as well as the subsequent severity of acne. for example, a study from brazil demonstrated 45 percent of women who used makeup daily had a distinguished dermatosis. approximately 14 percent of these patients suffered specifically from acne cosmetica.11 similarly, a study by perera et al was conducted to determine the effect of makeup usage on acne severity. in their study of 140 adolescent girls from 3 different schools in colombo, sri lanka, a statistically significant correlation was demonstrated between cosmetic exposure and acne grade. only 8.6% of the study population was free of acne (grade 0), whereas the remaining majority (91.4%) obtained a high intensity acne grading. these results suggest that regular cosmetic usage might be a causative factor for acne in post-pubertal girls, and reduction in makeup application may reduce the severity of acne.12 however, there is increasing interest in cosmetic products as components of acne patients’ overall management plans, which can complement the medical regimen.13 in females, in particular, there is a need for cosmetic products that can effectively cover the signs of this highly visible skin condition to reduce the emotional impact of the disease. use of cosmetics can also increase acne patients’ adherence with their medical regimen, which is estimated to be poor in 50% of patients.14 therefore, we see that people with acne tend to use makeup more often to cover their blemishes while also taking medications that help subside acne. ingredients and vehicle of makeup traditionally, researchers and dermatologists have advised individuals with oily or acne-prone skin to refrain from using moisturizers, foundations and other personal care items consisting of comedogenic or oilbased products. these ingredients may lead to the clogging of pores and ultimately to the formation of acne. similarly, acne patients have been advised to refrain from products that are thick and creamy in consistency as they may also clog pores. unfortunately, even the use of a robust facial cleanser, face wash or makeup removing wipes has little to no effect on controlling acne if comedogenic makeup is used routinely.15 we also suggest dermatologists to advise methods discussion skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 477 patients to make sure to wash all makeup application accessories and tools, including brushes, beauty blenders and powder puffs frequently with a mild non-comedogenic cleanser or face wash and allowing them to air dry. clean makeup application brushes will ensure minimal clogging of pores that usually results from layers of old makeup products embedded in these brushes. the comedogenic scale comedogenicity indicates the potential to lead to formation of comedones and development of acne. finished products containing high comedogenicity ingredients should be evaluated for their comedogenic potential.. in an effort to better understand the effect of makeup ingredients and their future acne forming capabilities, the comedogenic scale was devised. the comedogenic scale rates the active ingredients of different makeup and skincare formulations based on their propensity to clog pores. the scale uses a numbering system of 0 to 5, with 0 being the lowest and 5 being the highest.16 the comedogenic scale: 0 won’t clog pores at all 1 very low likelihood of clogging pores 2 moderately low likelihood 3 moderate likelihood 4 fairly high likelihood 5 high likelihood of clogging pores non-comedogenic products that do not clog pores have a comedogenic rating of 2 or less. makeup with a moderate (3) to high comedogenic (5) score should be avoided in teens with acne prone skin as it greatly increases the probability of an acne breakout or the worsening of acne in those who have acne prone skin.16 some common makeup ingredients implicated in the pathogenesis of acne are listed below along with their comedogenicity. algae extract algae extract can be found in some concealers and moisturizers. it is rated as 5 on the comedogenic scale. products containing algae extract should be avoided in acne because of its high tendency to clog pores and irritate the skin, causing redness and itching.17 benzaldehyde benzaldehyde is an added fragrance used in cosmetics and skincare products. it is rated as 3.5 on the comedogenic scale and leads to clogged pores and irritated skin. this effect may be seen with other fragrances commonly used in cosmetics and skin care products.18 d&c red d & c red is a dye added to give color to cosmetics. this dye is commonly found in blushes or bronzers, which may explain the predominance of cosmetic acne in the cheekbone area.16 this will be seen as ‘d & c red’ on the label and followed by a number. numbers 27 and 40 are rated high on the scale, whereas the others are rated as medium on the scale. interestingly, the vehicle carrying d&c determines its comedogenic grade. for instance, polyethylene glycol is less comedogenic than d&c red when incorporated into other vehicles such as mineral oil.19 silicones there are numerous silicone variations found in beauty products, including but not limited to methicone, dimethicone, trimethicone, and cyclomethicone. these skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 478 ingredients create a silky, smooth feel and are often found in cosmetic primers, deodorants, sunscreens, and leave-in hair styling products. sensitive and acne-prone skin can end up with breakouts if silicone is used regularly, since it may lead to the clogging of pores.20 coconut and avocado oil both coconut and avocado oil have long been used as a “natural” alternative for providing skin and hair with a radiant glow, but they are responsible for the formation of comedones due to their occlusive properties. moreover, these oils are both difficult to remove, thus adding to their occlusive and pore-clogging nature. these oils have a high comedogenic index of 3-4.19 isopropyl isostearate isopropyl isostearate is an emollient found in many lotions and skin care products. it is ranked the highest on the comedogenic scale with a score of 5. isopropyl isostearate is the ester of isopropyl alcohol (rubbing alcohol) and stearic acid (a thickening agent) and is most commonly found in skin care products and eye cosmetics.20 products for acne prone skin thankfully, many moisturizers and cosmetics are now being designed for acne prone skin types. specifically, these products incorporate non-comedogenic ingredients along with a water base that can provide full coverage to acne lesions and scars without causing a detrimental effect to the skin by aggravating breakouts by the blockage of pores.21 some of these makeup products also contain ingredients aimed at treating acne such as salicylic acid. in general, it is recommended to use an oil-free makeup with light consistency to prevent breakouts. some other key ingredients patients may benefit from in their cosmetic products include hyaluronic acid, retinol, lascorbic acid, sulfur and minerals.22 below, we have included a list of studied ingredients that are helpful in alleviating as well as preventing acne onset. salicylic acid salicylic acid is lipophilic acid with beta hydroxyl acid capabilities. it has played a role in acne prevention for many years and has gained popularity as the main ingredient in many commercially available facial cleansers. salicylic acid is less irritating than skin care products containing alpha-hydroxy acids, while providing similar improvement in skin texture and color. the ability of salicylic acid to exfoliate the stratum corneum along with its comedolytic property makes it a useful peeling agent for acne. salicylic acid is known to disrupt cellular junctions— desmosomes, without lysing intercellular keratin filaments.23 given the accessibility of salicylic acid, there are many over the counter skin care products that may be beneficial for those with acne prone skin. hyaluronic acid hyaluronic acid (ha), a glycosaminoglycan, is known for its tendency to keep skin plump and supple due to its humectant capabilities while preventing acne breakouts. hyaluronic acid plays a vital role in the synthesis of extracellular matrix molecules and epidermal cell interaction with the surrounding environment. it modulates cellular immunity by preventing bacterial infections and halting allergic reactions. its most important property is to hydrate the skin by holding large amounts of moisture in the dermis. hyaluronic acid is a component of the body's connective tissues, and is known to cushion and lubricate. with skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 479 aging, however, the amount of hyaluronic acid found naturally within the dermis decreases to about five percent of baseline.24 skin care products often couple hyaluronic acid with vitamin c products to assist in penetration. retinol retinol is derived from vitamin a and is increasing in popularity in many over-thecounter skin care products aimed at acne as well as “anti-aging”. retinol has a molecular structure small enough to penetrate the skin to the deep layers to interact with collagen and elastin. retinol also binds to specific proteins in the nucleus of skin cells which allows it to influence the transcription of many genes and transcription factors.25 the overall effect of retinol includes, but is not limited to, correction of skin pigmentation, a decrease in the appearance of fine lines and wrinkles due to increased collagen synthesis, and reduction of sun damage and inflammation. cosmetic products may also use retinyl palmitate which is closely related to retinol, but is less potent. topical retinoids, as monotherapy, are mainly used in patients with noninflammatory comedones, in combination with other topical and systemic drugs in mild, moderate, and severe inflammatory acne, and also as a maintenance treatment when oral treatment is stopped. the following retinoid molecules are used today in the topical management of acne: tretinoin (alltrans retinoic acid), isotretinoin (13-cis isomer), adapalene, tazarotene, and retinaldehyde.25 l-ascorbic acid l-ascorbic acid (laa) is the chemically active form of vitamin c. vitamin c is a potent antioxidant that can be used topically to treat and prevent changes associated with photo aging. it can also be used for the treatment of hyper-pigmentation resulting from acne scars. l-ascorbic acid interacts with copper ions at the tyrosinase-active site and inhibits action of the enzyme tyrosinase, thereby decreasing the melanin formation resulting in decreased hyperpigmentation. vitamin c has also been shown to stimulate the synthesis of collagen by stimulating lipid peroxidation. the by-product of this stimulation, malondialdehyde, in turn stimulates collagen gene expression. vitamin c also directly activates the transcription of collagen synthesis and stabilizes pro-collagen mrna, thereby regulating collagen synthesis.26 sulfur or sulfacetamide sodium sulfacetamide 10%-sulfur 5% (sss) emollient in face wash and cleanser works by stopping the growth of certain bacteria on skin including propionibacterium acnes. it is also known to exhibit moisturizing properties. in addition, sss emollient foam has been shown to markedly reduce colony counts of propionibacterium acnes in vitro.27 a summary of dermatologic recommendations for acne cosmetica although it is best to keep acne prone skin bare as much as possible, patients may feel the pressure or desire to conceal their lesions. this is achievable with the right choice of skincare and beauty products such as foundation and concealer, along with mastery in makeup application techniques. however, we suggest it is beneficial for the dermatologist to advise patients to make sure to frequently wash all makeup application accessories and tools, including brushes, beauty blenders and powder puffs with a mild non-comedogenic cleanser or face wash. while there are many products skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 480 available on the market to combat acne vulgaris, a robust understanding of the active ingredients in skincare and beauty products is necessary to help patients struggling with acne vulgaris. in short, patients with acne should avoid product ingredients such as avocado and coconut oil, silicones, isopropyl isostearate, d&c red, benzaldehyde and algae extract for skin use. instead, it is recommended that products containing ingredients such as lascorbic acid, hyaluronic acid, salicylic acid, retinol, and sulfur be used in acne-prone patients to help reduce inflammation. in conclusion, there are various advantages and disadvantages associated with makeup use in acne. makeup can damage sensitive and acne-prone skin if used daily and excessively however, the use of dermatologist enforced non-comedogenic makeup may help conceal acne induced blemishes, and therefore boost selfconfidence in adolescents who may otherwise feel uncomfortable going out with bare skin. there is a pressing need for dermatologists and patients to select appropriate, well-tolerated, and noncomedogenic skin care and makeup products containing active ingredients that help to eradicate acne. we recommend that acne-prone individuals consult dermatologists prior to buying makeup and skincare products to help determine whether product ingredients are safe to use with no risk of causing skin inflammation, and to also determine its efficacy in improving skin conditions. finally, dermatologists should emphasize the importance of utilizing prescription topical medications consisting of key dermatocosmetic ingredients that control acne, such as retinol and salicylic acid, so that patients with acne can notice visible results over time. conflict of interest disclosures: none funding: none corresponding author: hira ghani 940 n new st. bethlehem, pa 18018 phone: 201-925-5165 email: hghani01@nyit.edu references: 1. lynn dd, umari t, dunnick ca, dellavalle rp. the epidemiology of acne vulgaris in late adolescence. adolesc health med ther. 2016;7:13–25. 2. skroza n, tolino e, mambrin a, et al. adult acne versus adolescent acne: a retrospective study of 1,167 patients. the journal of clinical and aesthetic dermatology. 2018;11(1):21-25. 3. wischhover c. a dermatologist explains all the ways to treat acne. racked website. www.racked.com/2018/4/12/17179550/popularacne-treatments-dermatologist-aad. accessed november 20, 2020. 4. li x, he congfen, chen z, zhou c, gan y, jia y. a review of the role of sebum in the mechanism of acne pathogenesis. journal of cosmetic dermatology. 2017;16(2):168-173. 5. zaenglein al, pathy al, schlosser bj, et al. guidelines of care for the management of acne vulgaris. j am acad dermatol. 2016;74:945. 6. tanghetti ea. the role of inflammation in the pathology of acne. j clin aesthet dermatol. 2013;6(9):27–35. 7. kucharska a, szmurło a, sińska b. significance of diet in treated and untreated acne vulgaris. postepy dermatol alergol. 2016;33(2):81–86. 8. revenue of the cosmetic and beauty industry in the united states from 2002 to 2020. statista website. www.statista.com/statistics/243742/revenue-ofthe-cosmetic-industry-in-theus/#:~:text=the%20revenue%20of%20the%20u. s.,billion%20u.s.%20dollars%20in%202019.&text =since%20the%20early%20twentieth%20century, handful%20of%20multi-national%20corporations. accessed december 24, 2020. 9. kligman am, mills oh. acne cosmetica. arch dermatol. 1972 dec;106(6):843-850. conclusion mailto:hghani01@nyit.edu http://www.racked.com/2018/4/12/17179550/popular-acne-treatments-dermatologist-aad http://www.racked.com/2018/4/12/17179550/popular-acne-treatments-dermatologist-aad http://www.statista.com/statistics/243742/revenue-of-the-cosmetic-industry-in-the-us/#:~:text=the%20revenue%20of%20the%20u.s.,billion%20u.s.%20dollars%20in%202019.&text=since%20the%20early%20twentieth%20century,handful%20of%20multi-national%20corporations http://www.statista.com/statistics/243742/revenue-of-the-cosmetic-industry-in-the-us/#:~:text=the%20revenue%20of%20the%20u.s.,billion%20u.s.%20dollars%20in%202019.&text=since%20the%20early%20twentieth%20century,handful%20of%20multi-national%20corporations http://www.statista.com/statistics/243742/revenue-of-the-cosmetic-industry-in-the-us/#:~:text=the%20revenue%20of%20the%20u.s.,billion%20u.s.%20dollars%20in%202019.&text=since%20the%20early%20twentieth%20century,handful%20of%20multi-national%20corporations http://www.statista.com/statistics/243742/revenue-of-the-cosmetic-industry-in-the-us/#:~:text=the%20revenue%20of%20the%20u.s.,billion%20u.s.%20dollars%20in%202019.&text=since%20the%20early%20twentieth%20century,handful%20of%20multi-national%20corporations http://www.statista.com/statistics/243742/revenue-of-the-cosmetic-industry-in-the-us/#:~:text=the%20revenue%20of%20the%20u.s.,billion%20u.s.%20dollars%20in%202019.&text=since%20the%20early%20twentieth%20century,handful%20of%20multi-national%20corporations http://www.statista.com/statistics/243742/revenue-of-the-cosmetic-industry-in-the-us/#:~:text=the%20revenue%20of%20the%20u.s.,billion%20u.s.%20dollars%20in%202019.&text=since%20the%20early%20twentieth%20century,handful%20of%20multi-national%20corporations skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 481 10. murakami-yoneda y, hata m, shirahige y, nakai k, kubota y. effects of makeup application on diverting the gaze of others from areas of inflammatory lesions in patients with acne vulgaris. journal of cosmetics, dermatological sciences and applications. 2015;5(2):134-141. 11. alvarez manny. the damaging effects makeup can have on teens. new york post website. https://nypost.com/2017/06/17/the-damagingeffects-makeup-can-have-on-teens/. accessed november 12, 2020. 12. perera mpn, peiris wmdm, pathmanathan d, mallawaarachchi s, karunathilake im. relationship between acne vulgaris and cosmetic usage in sri lankan urban adolescent females. j cosmet dermatol. 2018;17(3):431-436. 13. del rosso jq. the role of skin care as an integral component in the management of acne vulgaris: part 1: the importance of cleanser and moisturizer ingredients, design, and product selection. j clin aesthet dermatol. 2013;6(12):19–27. 14. dreno b, thiboutot d, gollnick h, et al. largescale worldwide observational study of adherence with acne therapy. int j dermatol. 2010;49(4):448–456. 15. cichowski heather. watch out for these skin care ingredients if you have acne-prone skin. the fashion spot website. www.thefashionspot.com/beauty/787783ingredients-that-cause-acne. accessed october 29, 2020. 16. fulton je jr, pay sr, fulton je 3rd. comedogenicity of current therapeutic products, cosmetics, and ingredients in the rabbit ear. j am acad dermatol. 1984 jan;10(1):96-105. 17. narayan v. holistic skincare and selection of skincare products in acne. archives of clinical & experimental dermatology. 2020; 2(1);1-3. 18. maharani a, pratiwi w, nauphar d. changing cosmetic brands increase risk of frequency and degree of acne vulgaris in female undergraduate students. proceedings of international conference on applied science and health. 2018; 3:53-57. 19. rubin i, maged g, garruto j, mccarver b. noncomedogenic and non-acnegenic hair and scalp care formulations and method for use. www.patents.google.com/patent/us9949915b2/en . accessed december 13, 2020. 20. simion, fa. acnegenicity and comedogenicity testing for cosmetics. handbook of cosmetic science and technology. 2001; 837-844. 21. chularojanamontri l, tuchinda p, kulthanan k, pongparit k. moisturizers for acne: what are their constituents? j clin aesthet dermatol. 2014;7(5):36–44. 22. reszko anetta e, berson diane, lupo mary p. cosmeceuticals: practical applications. dermatol clin. 2009;27(4):401-416. 23. arif t. salicylic acid as a peeling agent: a comprehensive review. clin cosmet investig dermatol. 2015;8:455–461. 24. jegasothy sm, zabolotniaia v, bielfeldt s. efficacy of a new topical nano-hyaluronic acid in humans. j clin aesthet dermatol. 2014;7(3):27– 29. 25. rigopoulos d, ioannides d, kalogeromitros d, katsambas ad. comparison of topical retinoids in the treatment of acne. clin dermatol. 2004;22(5):408-411. 26. telang ps. vitamin c in dermatology. indian dermatol online j. 2013;4(2):143–146. 27. del rosso jq. the use of sodium sulfacetamide 10%-sulfur 5% emollient foam in the treatment of acne vulgaris. j clin aesthet dermatol. 2009;2(8):26–29. https://nypost.com/2017/06/17/the-damaging-effects-makeup-can-have-on-teens/ https://nypost.com/2017/06/17/the-damaging-effects-makeup-can-have-on-teens/ http://www.thefashionspot.com/beauty/787783-ingredients-that-cause-acne http://www.thefashionspot.com/beauty/787783-ingredients-that-cause-acne http://www.patents.google.com/patent/us9949915b2/en http://www.patents.google.com/patent/us9949915b2/en skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 152 brief article a case of amelanotic melanoma in the setting of cemiplimab therapy for invasive squamous cell carcinoma victoria lee, phd1, mark d. hoffman, md2, arlene m. ruiz de luzuriaga, md, mph2 1 pritzker school of medicine, university of chicago, chicago, il 2 section of dermatology, department of medicine, university of chicago, chicago, il cemiplimab is a monoclonal antibody directed against programmed-death receptor 1 (pd-1). it is the first pd-1 inhibitor approved in the united states for the treatment of metastatic or locally advanced cutaneous squamous cell carcinoma (scc) and basal cell carcinoma (bcc).1-4 although other pd-1 inhibitors have assumed important roles in the management of melanoma, cemiplimab does not currently have this indication. we describe a case of amelanotic melanoma developing in a patient on cemiplimab therapy for invasive scc. due to insufficient tyrosinase activity or quantity, cutaneous amelanotic melanoma (am) shows little or no melanin pigmentation on clinical and histological examination thus often leading to a high misdiagnosis rate.5 several studies have shown an association of ams with high mitotic and growth rates, and with higher prevalence of vertical growth phase and greater breslow scale at diagnosis than pigmented melanomas (pms), suggestive of an intrinsically aggressive phenotype.6,7 consequently, it is frequently diagnosed at advanced stages. a 72-year-old man presented for skin cancer surveillance. he had a history of basosquamous carcinoma (bsc) of the scalp with extension into the calvarium diagnosed 2.5 years earlier, which progressed following surgical resection and chemoradiotherapy. he had a complete response to 35 cycles of cemiplimab therapy over two years, and treatment was discontinued one month prior to presentation. on examination, a 6 mm pink papule was noted on the right arm (figure abstract cemiplimab is the first pd-1 inhibitor approved in the united states for the treatment of metastatic or locally advanced cutaneous squamous cell carcinoma (scc) and basal cell carcinoma (bcc), but not melanoma. we describe a case of amelanotic melanoma (am) developing in a patient on cemiplimab therapy for invasive scc. cutaneous am is a rare subtype of cutaneous melanoma that shows little or no melanin pigmentation on clinical and histological examination thus often leading to a high misdiagnosis rate. physicians should consider atypical presentations of melanoma, including amelanotic melanoma, during surveillance of patients managed with immune checkpoint inhibitor therapy. introduction case report skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 153 1). the patient believed this lesion had appeared in the past one to two months; his previous skin cancer surveillance had been 19 months earlier. the clinical concern was for bcc. figure 1. a 6mm pink papule noted on the right upper arm. histopathologic study of the shave biopsy led to a final diagnosis of malignant melanoma (clark level iv, breslow thickness at least 1 mm) with positive lateral and focally deep margins. the lesion was not heavily melanized (figures 2a and 2b). pd-l1 expression within the melanocytic lesion was high (>5% of tumor cells), with a heterogeneous expression pattern (figure 2c). brisk cd8+ tumor-infiltrating lymphocytes were observed in geographic association with high pd-l1 expression (figure 2d). the patient underwent wide local excision and sentinel lymph node biopsy. final pathology showed a residual melanoma in-situ component, with negative deep and lateral margins, and negative sentinel lymph nodes. unlike other pd-1 inhibitors in its class, cemiplimab is not presently indicated for the treatment of patients with advanced melanoma, though clinical trials of combination therapy with cemiplimab for this indication are currently underway.8 in our patient it appears that the am lesion arose during and near the completion of cemiplimab therapy. given that some immune checkpoint inhibitors are considered first-line therapy for unresectable or metastatic melanoma, it is striking that this melanoma was found in our patient after two years of treatment with a pd-1 inhibitor, and that it was clinically amelanotic and histologically poorly melanized. while amelanosis is not a feature known to be associated with resistance to pd-1 inhibitor therapy to date, vitiligo-like depigmentation has been associated with pd-1 inhibitors in the context of melanoma management, and this development has been linked to improved outcomes.9 interestingly, recognition of tyrosinase by tumor-infiltrating lymphocytes has been demonstrated in a melanoma patient responding to immunotherapy.10 as it is known that the lack of melanin pigmentation in am is due to insufficient tyrosinase activity or quantity,5 it is possible that the lesion observed in our patient progressed because it lacked a potential antigen for immune recognition. alternatively, it is also possible that recognition of tyrosinase by tumorinfiltrating lymphocytes during the course of receiving immunotherapy led to the destruction of tyrosinase-active melanized cells, thereby leaving behind an amelanotic lesion. discussion skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 154 figure 2. a) ×10 h&e staining showing proliferation of poorly melanized melanocytes with severe cytologic atypia extending into the dermis, and mitotic figures up to 7 per 1 mm2 b) ×10 immunohistochemical (ihc) staining with melan-a/ki67 showing pagetoid spread of melanocytes and increased proliferative activity within the dermis c) ×10 ihc staining with pd-l1 showing high expression within the melanocytic lesion (>5% of tumor cells) with heterogeneous expression pattern d) ×10 ihc staining with cd8 showing brisk cd8+ tumor-infiltrating lymphocytes in geographic association with high pd-l1 expression. the reliability of intratumoral pd-l1 expression as a predictive biomarker of response to pd-1/pd-l1 inhibitor therapy remains controversial.11,12 pd-l1 expression levels and patterns have been shown to vary across melanoma subtypes and morphology, and are often geographically associated with cd8+ lymphocytes, similar to our case.12 physicians should consider atypical presentations of melanoma, including amelanotic melanoma, during surveillance of patients managed with immune checkpoint inhibitor therapy. conflict of interest disclosures: none funding: none corresponding author: arlene m. ruiz de luzuriaga, md, mph 5841 s maryland ave, mc 5067 chicago, il 60637 email: aruizde@medicine.bsd.uchicago.edu conclusion skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 155 references: 1. migden mr, rischin d, schmults cd, et al. pd-1 blockade with cemiplimab in advanced cutaneous squamous-cell carcinoma. n engl j med 2018; 379(4):341-351. 2. migden mr, khushalani ni, chang als, et al. cemiplimab in locally advanced cutaneous squamous cell carcinoma: results from an openlabel, phase 2, single-arm trial. lancet oncol 2020; 21(2):294-305. 3. ahmed sr, petersen e, patel r, et al. cemiplimab-rwlc as first and only treatment for advanced cutaneous squamous cell carcinoma. expert rev clin pharmacol 2019; 12(10):947951. 4. stratigos aj, sekulic a, perris k, et al. cemiplimab in locally advanced basal cell carcinoma after hedgehog inhibitor therapy: an open-label, multi-centre, single-arm, phase 2 trial. lancet oncol 2021; s1470-2045(21):00126-1. 5. gong h, zheng h, li j. amelanotic melanoma. melanoma res 2019; 29(3):221-230. 6. thomas ne, kricker a, waxweiler wt, et al. comparison of clinicopathologic features and survival of histopathologically amelanotic and pigmented melanomas: a population-based study. jama dermatol 2014; 150(12):1306– 1314. 7. mcclain se, mayo kb, shada al, et al. amelanotic melanomas presenting as red skin lesions: a diagnostic challenge with potentially lethal consequences. int j dermatol 2012; 51(4):420-426. 8. clinical trials using cemiplimab [internet]. national cancer institute; n.d. [cited 2021 jun 2]. available from: https://www.cancer.gov/aboutcancer/treatment/clinicaltrials/intervention/cemiplimab 9. teulings h, limpens j, jansen sn, et al. vitiligolike depigmentation in patients with stage iii-iv melanoma receiving immunotherapy and its association with survival: a systematic review and meta-analysis. j clin oncol 2015; 33(7):773-781. 10. robbins pf, el-gamil m, kawakami y, et al. recognition of tyrosinase by tumor-infiltrating lymphocytes from a patient responding to immunotherapy. cancer res 1994; 54:31243126. 11. long gv, larkin j, ascierto pa, et al. pd-l1 expression as a biomarker for nivolumab (nivo) plus ipilimumab (ipi) and nivo alone in advanced melanoma (mel): a pooled analysis. ann oncol 2016; 27(6_suppl):1112pd–pd. 12. kaunitz gj, cottrell tr, lilo m, et al. melanoma subtypes demonstrate distinct pd-l1 expression profiles. laboratory investigation 2017; 97:10631071. skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 156 introduction • rosacea is a chronic, inflammatory, facial skin condition affecting approximately 16 million people in the united states1,2 • topical therapies such as metronidazole and azelaic acid are considered firstline options for the treatment of papulopustular rosacea2-5 • oral tetracyclines, doxycycline and minocycline, are mainstays of treatment; however, they are associated with significant systemic side effects2,4 • fmx103 1.5% is a topical minocycline foam that was developed for the treatment of moderate-to-severe papulopustular rosacea. efficacy and safety have been established in: – a phase 2 clinical trial – 2 pivotal, identical, phase 3, double-blind, vehicle-controlled studies (study fx2016-11 and study fx2016-12) • a phase 1 open-label study (fx2017-14) was conducted to evaluate minocycline’s pharmacokinetic (pk) and safety profile following multiple-dose topical administration of fmx103 1.5% minocycline foam for moderate-tosevere facial papulopustular rosacea – single-center, nonrandomized trial – 14 days, maximum-use conditions • this report presents data from the completed pk and safety study methods • fx2017-14, a phase 1, single-center, nonrandomized, single-period, pk and safety evaluation study of fmx103 1.5% topical minocycline foam in the treatment of moderate-to-severe facial papulopustular rosacea (figure 1) – fmx103 1.5% foam applied daily to full face for 14 days – 20 subjects – approximately 2 grams of fmx103 1.5% figure 1. study design methods ➢ fx2017-14, a phase 1, single-center, nonrandomized, single-period, pk and safety evaluation study of fmx103 1.5% topical minocycline foam in the treatment of moderate-to-severe facial papulopustular rosacea (figure 1) ➢ fmx103 1.5% foam applied daily to full face for 14 days ➢ 20 subjects ➢ approximately 2 grams of fmx103 1.5% figure 1. study design 3 fx2017-14 fmx103 1.5% (n=20) baseline day 1 day 6 day 9 day 11 day 12 day 14 (end of treatment) inclusion criteria ➢ males and nonpregnant females ≥18 years ➢ moderate-to-severe facial papulopustular rosacea (iga score of 3 or 4) ➢ presence or history of facial erythema or flushing pharmacokinetic evaluation ➢ pk blood samples: pre-dose at 30 minutes prior to administration on day 1, 6, 9, 11, 12, and 14; and post-dose at 2, 4, 8, 12, 16, and 24 hours after administration of study drug safety evaluation ➢ teaes, clinical laboratory tests, vital signs, physical examinations, clinical laboratory tests, and iga scores iga=investigator’s global assessment; teae=treatment-emergent adverse event.iga=investigator’s global assessment; teae=treatment-emergent adverse event. results • 20 subjects enrolled in the study • baseline demographics and disease characteristics are shown in table 1 table 1. baseline demographics and disease characteristics fmx103 1.5% (n=20) mean age, years 47.3 male, n (%) female, n (%) 6 (30.0) 14 (70.0) race, n (%) white 20 (100) iga score, n (%) 3 – moderate 4 – severe 18 (90.0) 2 (10.0) table 2. summary of pk parameters fmx103 1.5% (n=19)* pk parameter day 1 mean (sd) day 14 mean (sd) c max (ng,ml) 1.30 (0.92) 0.75 (0.54) t max (h) 11.8 (4.07) 9.5 (3.82) auc 0-tldc (ng*h/ml) 21.3 (16.2) 23.1 (34.1) c 24 (ng/ml) 0.86 (0.64) 0.57 (0.42) auc 0-tau (ng*h/ml) 22.5 (16.2) 15.8 (11.4) r acc na 0.77 (0.34) *1 subject had all plasma concentrations below the limit of quantification. auc0-tau = area under the concentration-time curve from time zero (predose) through 24 hours; auc0 -tldc = area under the concentration-time curve from time zero (pre-dose) to the time of last determinable concentration; c24 = plasma minocycline concentration 24 hours after fmx103 1.5% application; cmax = maximum observed plasma concentration; racc = accumulation ratio; sd = standard deviation; tmax = time to maximum measured plasma concentration. table 3. study drug concentrations by time points in pk population, day 1 to day 14 visit time point fmx103 1.5% (n=20) mean (sd) day 1 pre-dose 2 hours post-dose 4 hours post-dose 8 hours post-dose 12 hours post-dose 16 hours post-dose 0.05 (0.20) 0.24 (0.36) 0.70 (0.75) 1.09 (0.89) 1.13 (0.96) 0.98 (0.77) day 2 24 hours post-dose 0.78 (0.66) day 6 pre-dose 0.38 (0.40) day 9 pre-dose 0.37 (0.38) day 11 pre-dose 0.44 (0.37) day 12 pre-dose 0.40 (0.33) day 14 pre-dose 2 hours post-dose 4 hours post-dose 8 hours post-dose 12 hours post-dose 16 hours post-dose 0.34 (0.37) 0.40 (0.45) 0.53 (0.51) 0.62 (0.53) 0.61 (0.60) 0.56 (0.51) table 4. study drug concentrations by time points in pk population, 24 to 96 hours after final treatment with fmx103 1.5% visit time point fmx103 1.5% (n=20) mean (sd) day 15 24 hours post-dose 0.45 (0.44) day 16 48 hours post-dose 0.16 (0.35) day 17 72 hours post-dose 0.09 (0.27) day 18 96 hours post-dose 0.07 (0.32) figure 2. linear plot of mean plasma minocycline concentration, day 1 and day 14 following application of fmx103 1.5% figure 2. linear plot of mean plasma minocycline concentration, day 1 and day 14 following application of fmx103 1.5% results (cont.) 8 lloq=lower limit of quantification. p la sm a m in oc yc lin e c on ce nt ra tio n (n g/ m l) ± s d 2.4 2.0 1.6 1.2 0.8 0.4 0.0 -0.4 day 1 day 14 20 20 20 20 20 20 20 20 20 20 20 20 20 20 20 0 2 4 8 12 16 24 48 hours post-administration day 1 day 14 lloq 20 72 20 96 lloq=lower limit of quantification. figure 3. linear plot of mean plasma trough concentrations of minocycline 0.20 figure 3. linear plot of mean plasma trough concentrations of minocycline results (cont.) 9 1 6 9 11 12 14 predose 14 postdose tr ou gh p la sm a c on ce nt ra tio n of m in oc yc lin e (n g/ m l) + /– s d days 0.80 0.60 0.40 20 20 20 20 20 20 20 0 pharmacokinetics summary • after daily application of fmx103 1.5%, pk parameters of minocycline were generally similar for day 1 and day 14. plasma concentrations of minocycline were low across the study (table 2) • day 1 and day 14 plasma concentrations demonstrated a pk profile consistent with the dosing of fmx103 1.5%. the mean (sd) values for the maximum observed plasma concentration (cmax) were approximately 1.30 ng/ml on day 1 and 0.75 ng/ml on day 14 (tables 2-4; figure 2) • trough levels were approximately 0.5 ng/ml overall, from 24 hours after the first dose through 24 hours after the day 14 dose; mean (sd) values ranged from 0.34 (0.37) ng/ml to 0.78 (0.66) ng/ml (table 3; figure 3) • steady-state appeared to be achieved within 1 day table 5. summary of teaes in the all-treated population fmx103 1.5% (n=20) subjects with any teae, n (%) number of teaes 1 (5.0) 2a subjects with any treatment-related teae, n (%) number of treatment-related teaes 1 (5.0) 1b subjects with any serious teae, n (%) number of serious teaes 0 0 subjects with any severe teae, n (%) number of severe teaes 0 0 subjects with any teae leading to discontinuation of study, n (%) number of teaes leading to discontinuation 0 0 aarthralgia, headache. bheadache. table 6. teaes in the all-treated population fmx103 1.5% (n=20) one or more teaes, n (%) 1 (5.0) adverse events, n (%) arthralgia 1 (5.0) headache 1 (5.0) safety summary • fmx103 1.5% was generally safe and well tolerated • all 20 subjects completed the study • there were no serious teaes, no severe teaes, and no teaes that resulted in the study drug being withdrawn or requiring a dose reduction (table 5) • 1 subject reported 2 teaes: arthralgia, which was thought to be unrelated to the study drug, and a mild headache, considered possibly related to the study drug (table 6) conclusions • the results of the phase 1 pk and safety evaluation study showed that fmx103 1.5% was safe and well tolerated by subjects with moderate-tosevere facial papulopustular rosacea • once-daily topical application of approximately 2 grams of fmx103 1.5% for 14 days yielded low plasma concentrations of minocycline over time and a pk profile consistent with dosing • teaes were reported in 1 subject, but there were no serious or severe teaes, and no subjects discontinued or required dose reductions secondary to a teae references 1. li wq, cho e, khalili h, et al. rosacea, use of tetracycline, and risk of incident inflammatory bowel disease in women. clin gastroenterol hepatol. 2016;14(2):220-225. 2. taieb a, gold ls, feldman sr, et al. cost-effectiveness of ivermectin 1% cream in adults with papulopustular rosacea in the united states. j manag care spec pharm. 2016;22(6):654-665. 3. rainer bm, kang s, chien al. rosacea: epidemiology, pathogenesis, and treatment. dermatoendocrinology. 2018;9(1). 4. oge lk, muncie hl, phillips-savoy ar. rosacea: diagnosis and treatment. am acad fam physicians. 2015;92(3). 5. schaller m, schofer h, homey b, et al. rosacea management: update on general measures and topical treatment options. j german soc dermatol. 2016;14(suppl 6):17-27. disclosures this study was funded by foamix pharmaceuticals, inc. terry jones, md, served as the principal investigator on the study. iain stuart, phd, is an employee of foamix pharmaceuticals. acknowledgment editorial support was provided by maryann meleka, md, from p-value communications. pharmacokinetics of minocycline foam fmx103 in subjects with moderate-to-severe facial papulopustular rosacea under maximum-use conditions: results of a phase 1 study terry m. jones, md,1 iain stuart, phd2 1j&s studies, inc., college station, texas, usa; 2foamix pharmaceuticals, inc., bridgewater, new jersey, usa poster presented at the winter clinical dermatology conference; january 18-23, 2019; koloa, hawaii. skin may 2018 volume 2 issue 3 copyright 2018 the national society for cutaneous medicine 162 original research electrical impedance spectroscopy versus clinical inspection approaches: melanoma efficacy detection comparison ryan m. svoboda md ms a , abigail i. franco md b , darrell s. rigel md ms c a national society for cutaneous medicine, new york, ny b st. joseph’s hospital, syracuse, ny c ronald o. perelman department of dermatology, nyu school of medicine, new york, ny early detection and excision remain the most important prognostic factors in the treatment of melanoma. 1 detection remains challenging and, resultantly, melanomarelated mortality is high. in 2017, an estimated 9,730 people will die from melanoma in the united states. 2 accordingly, there has been significant interest in novel technologies aimed at augmenting the detection rate achieved with clinical diagnosis of melanoma. 3 electrical impedance spectroscopy (eis) (nevisense, scibase ab, stockholm, sweden) has been shown to have potential as a diagnostic aid for the detection of melanoma. 4,5 in the current study, we examined a subset of data from an international, multicenter, trial 4 in order to compare the sensitivity of eis to abstract early detection of melanoma continues to provide a diagnostic challenge for dermatologists and other healthcare providers. recently, there has been increased interest in the use of novel technology to aid in the detection of melanoma. we performed a post-hoc analysis of a subset of data from the nevisense pivotal trial to retrospectively compare the results of one such technology—electrical impedance spectroscopy (eis)—to existing melanoma detection tools in 265 cases of malignant melanoma. lesions were analyzed using eis, the clinical abcd rule, the abcd dermoscopy rule, and the standard and weighted melanoma 7-point checklists. the proportion of false negative cases was calculated for each method and correlation between eis score and melanoma stage was calculated. overall, eis produced an acceptable false negative rate (3.4%) for the detection of melanoma. additionally, there was a statistically significant, moderate correlation between eis score and tumor staging (spearman rho=0.32, p<0.001). in this sample, eis was very sensitive for the detection of melanoma and may prove to be a useful clinical adjunct for ruling out malignant melanoma in challenging cases. introduction skin may 2018 volume 2 issue 3 copyright 2018 the national society for cutaneous medicine 163 existing melanoma detection tools and to measure the enhancement in sensitivity of melanoma detection achieved by combining eis with other methods. additionally, we determined the correlation between eis score and pathologic staging in biopsyproven melanoma lesions. of the 1,943 pigmented lesions evaluated in a prior series 4 , the 265 biopsy-proven melanoma lesions (112 in situ, 153 invasive melanoma) were selected for inclusion in this sub-analysis. prior to excisional biopsy, using the eis device, lesions had been measured on a 0-10 scale, with a score of 4 or greater representing a positive score. prior to biopsy, dermoscopic images were saved and these were analyzed in a postexcisional performance study of those lesions with sufficient image quality to allow classification using the clinical abcd rule, the abcd rule of dermoscopy (cutoff >4.75 for positive score), and both the melanoma 7-point checklist and the weighted 7-point checklist (cutoff ≥3 for positive score). twenty-seven of the biopsy-proven melanoma lesions did not have sufficient image quality to allow classification by each of these methods and were thus excluded, leaving a total of 238 melanoma lesions (101 in situ, 137 invasive). false negative rate was calculated for each method. additionally, correlation between eis score and pathologic stage (taking into account all 265 biopsy-proven melanoma lesions assessed with eis) was measured using spearman’s rho. the false negative rate for the detection of melanoma by visual inspection has been estimated to be approximately 20-30%. 6-8 in the present study, there were 9 false negative results by eis (false negative rate 3.4%, sensitivity 96.6%). all false negative eis results occurred in early lesions (7 in situ, 2 t1a). in this sample, there was also a trend towards lower false negative rate with eis versus that of the clinical abcd rule, although the result was not statistically significant (3.4% vs. 12.8%, p=0.294). the false negative rate for the detection of melanoma by eis was statistically significantly lower compared to the abcd rule of dermoscopy (3.4% vs. 45.8%, p=0.003), the 7-point checklist (3.4% vs. 50.8%, p=0.008), and the weighted 7-point checklist (3.4% vs. 39.3%, p=0.001) (figure 1). the clinical abcd rule was the only method that detected melanoma lesions that were missed by eis (6 lesions). however, eis detected more lesions that were missed by the clinical abcd rule (31 lesions). there was a statistically significant, moderate correlation between eis score and tumor staging (rho=0.32, p<0.001, figure 2). methods results skin may 2018 volume 2 issue 3 copyright 2018 the national society for cutaneous medicine 164 figure 1. comparison of electrical impedance technology to other adjuncts to clinical diagnosis in the detection of malignant melanoma lesions. eis = electrical impedance spectroscopy. skin may 2018 volume 2 issue 3 copyright 2018 the national society for cutaneous medicine 165 figure 2. correlation between pathologic tumor stage and electrical impedance spectroscopy score in a sample of 265 biopsy-proven melanoma lesions. eis = electrical impedance spectroscopy. this subgroup analysis of biopsy-proven melanoma lesions from the pivotal study examining the clinical performance a novel eis system demonstrates that the false negative rate of eis for the detection of melanoma is quite low, making this tool potentially useful as a method of ruling out malignancy in equivocal pigmented skin lesions. 4 additionally, when combined with other adjunctive methods (as would be done in a real-world setting), eis has the potential to increase sensitivity for detection of melanoma. however, it is important to remember that when combining two techniques such as eis and dermoscopy, sensitivity for detection will increase relative to each individual technique at the cost of a lower combined specificity compared to each individual technique (because the number of false positive lesions will increase). thus, the benefit of increased sensitivity (lower likelihood of missing a melanoma lesion) must be considered in the context of the detriment of decreased specificity (higher likelihood of performing additional, unnecessary biopsies). this is particularly important given the relatively lower overall specificity of eis (35.8%) versus the adjunctive methods (94.0% for abcd dermoscopy and 94.2% for the seven-point checklist) in the pivotal trial. 4 thus, it is important that eis be used as an adjunct to aid in ruling out melanoma in equivocal lesions rather than a sole means of diagnosis. it must be considered in the discussion skin may 2018 volume 2 issue 3 copyright 2018 the national society for cutaneous medicine 166 context of the entire clinical picture. however, given the higher costs to an individual and society of a missed melanoma compared to a negative biopsy, eis should be considered when the benefits are felt to outweigh the risks by the seasoned clinician (e.g. high-risk patients with equivocal lesions). additionally, the moderate correlation between eis score and stage in this study provides useful information. lesions with lower eis scores still in the range of positive are more likely to represent in situ and t1 lesions, although a high score does not necessarily mean an advanced lesion. further, in this sample, all melanomas that were false negatives by eis were early stage lesions. there are several limitations to this study in addition to the considerations surrounding specificity mentioned above. first, although all included lesions were suspicious and underwent clinical evaluation (which may have included use of adjunctive tools such as dermoscopy) to guide the decision to biopsy, the data from the adjunctive methods in this study comes from postexcisional analysis of the dermoscopic images. the clinicians interpreting the dermoscopic images were not privy to a full skin examination of the patient. thus, the decision-making did not completely simulate a real-life clinical scenario, in which a provider would perform a clinical and dermoscopic exam while considering the context of the remainder of the patient history and clinical exam. second, all lesions included were deemed clinically suspicious and scheduled for excisional biopsy (an inclusion criteria for the original study). thus, the lesions examined by dermoscopy may not be reflective of the larger population of lesions for which this technique would be employed in standard practice. however, eis technology is meant to be utilized by trained dermatologists to examine clinically equivocal lesions, so the comparison in this study is likely akin to that of a real-world setting. additionally, the dataset utilized in this post-hoc analysis included only the biopsy-proven melanomas from the original pivotal trial; thus, specificity could not be calculated directly in this sub-analytic study. eis may produce a lower incidence of false negative results than common diagnostic adjuncts for the detection of melanoma. further, there appears to be a moderate correlation between eis score and pathologic stage. combining eis with clinical evaluation and other adjunctive tools may improve the sensitivity for the detection of melanoma, but this should be done when deemed clinically appropriate (e.g. high-risk patients) due to the resultant reduction in specificity. conflict of interest disclosures: dr. svoboda served on an advisory board without financial compensation for scibase ab. dr. rigel serves as a consultant and a member of the advisory board for scibase ab. dr. franco reports no conflicts of interest. funding: the raw data for this study was provided by scibase ab. there was no direct funding for this study but the original pivotal trial was funded by scibase ab. acknowledgements: the authors wish to acknowledge all of the investigators who took part in the original pivotal trial from which the data for this post-hoc analysis came. corresponding author: ryan m. svoboda, md, ms 35 e. 35 th st., ste. 208 new york, ny 11101 646-341-6468 212-689-5748 rmsvoboda@gmail.com conclusion skin may 2018 volume 2 issue 3 copyright 2018 the national society for cutaneous medicine 167 references: 1. glazer am, rigel ds, winkelmann rr, farberg as. clinical diagnosis of skin cancer: enhancing inspection and early recognition. dermatologic clinics. 2017;35:409-16. 2. cancer facts and figures 2017. 2017. (accessed september 13, 2017, at http://www.cancer.org/acs/groups/content/@edito rial/documents/document/acspc-048738.pdf.) 3. winkelmann rr, farberg as, glazer am, et al. integrating skin cancer-related technologies into clinical practice. dermatologic clinics. 2017;35:56576. 4. malvehy j, hauschild a, curiel-lewandrowski c, et al. clinical performance of the nevisense system in cutaneous melanoma detection: an international, multicentre, prospective and blinded clinical trial on efficacy and safety. br j dermatol. 2014;171:1099-107. 5. braun rp, mangana j, goldinger s, french l, dummer r, marghoob aa. electrical impedance spectroscopy in skin cancer diagnosis. dermatologic clinics. 2017;35:489-93. 6. friedman rj, gutkowicz-krusin d, farber mj, et al. the diagnostic performance of expert dermoscopists vs a computer-vision system on smalldiameter melanomas. arch dermatol. 2008;144:47682. 7. witheiler dd, cockerell cj. sensitivity of diagnosis of malignant melanoma: a clinicopathologic study with a critical assessment of biopsy techniques. exper dermatol. 1992;1:170-5. 8. grin cm, kopf aw, welkovich b, bart rs, levenstein mj. accuracy in the clinical diagnosis of malignant melanoma. arch dermatol. 1990;126:7636. synopsis • psoriasis is a chronic, systemic, immune-mediated disease of the skin that affects > 7.4 million people in the united states, with an estimated prevalence of 2% to 4%1 • secukinumab is a fully human monoclonal antibody that selectively neutralizes interleukin (il)-17a, a cornerstone cytokine involved in the development of psoriasis2 • secukinumab has demonstrated efficacy in clinical trails and effectiveness in real-world settings in the treatment of patients with psoriasis3-9 • however, there remain limited real-world data characterizing us patients with psoriasis who initiate secukinumab in routine clinical practice objective • to describe demographic and clinical characteristics of us patients with plaque psoriasis who initiated secukinumab in clinical practice, using clinical data obtained from the modernizing medicine data services (mmds) electronic medical records (emrs) dermatology panel methods study design and patient population • all data were collected from modernizing medicine’s electronic medical assistant (ema) system – ema delivers structured, real-world data captured from > 500,000 unique patients with psoriasis – data from emrs for patients in the united states with a clinical diagnosis of psoriasis were deidentified in accordance with hipaa (health insurance portability and accountability act) for research use • eligible patients in the mmds database had a diagnosis of plaque psoriasis during the study period of july 1, 2014, to march 31, 2018, had ≥ 1 prescription order for secukinumab within the index period (january 1, 2015, to september 30, 2017), and were aged ≥ 18 years at the time of secukinumab initiation (index date) • patients had ≥ 1 clinical visit for any reason during the 6-month pre-index (baseline) period and ≥ 1 clinical visit for any reason within the first and second 6 months following secukinumab initiation (12-month follow-up period) study variables and data analysis • demographic characteristics (age, sex, race, body weight, us region), treatment history (during 6-month pre-index period only), and clinical characteristics (comorbidities, psoriasis subtype, body surface area [bsa], and physician global assessment [pga]) were assessed by dermatology providers during the 6-month baseline period demographic and clinical characteristics of patients with plaque psoriasis initiating secukinumab in clinical practice: data from us dermatology electronic medical records paul s. yamauchi, md, phd,1 chi-chang chen, phd,2 yao ding, phd,2 rebecca germino, phd3 1ucla school of medicine, santa monica, ca; 2iqvia, plymouth meeting, pa; 3novartis pharmaceuticals corporation, east hanover, nj scan qr code to download this poster. presented at the 2019 winter clinical dermatology conference; january 18-23, 2019; koloa, hi. your document will be available for download at the following url: url: http://novartis.medicalcongressposters.com/default.aspx?doc=ecd09 and via text message (sms) text: qecd09 to : 8nova (86682) us only +18324604729 north, central and south americas; caribbean; china +447860024038 uk, europe & russia +46737494608 sweden, europe note: downloading data may incur costs which can vary depending on your service provider and may be high if you are using your smartphone abroad. please check your phone tariff or contact your service provider for more details. table 1. demographics of patients with psoriasis who initiated secukinumab and had 12 months of follow-up characteristic patients with 12-month follow-up (n = 4996) age, mean (sd), years 51.6 (13.7) male, n (%) 2524 (50.5) us region, n (%) south 2070 (41.4) west 1080 (21.6) midwest 1036 (20.7) northeast 802 (16.1) unknown 8 (0.2) race, n (%) white 3317 (66.4) black 141 (2.8) asian 129 (2.6) hispanic 92 (1.8) other/unknown 1317 (26.4) index year, n (%) 2015 1131 (22.6) 2016 2096 (42.0) 2017 1769 (35.4) comorbidities and treatment history during the baseline period • the most common comorbidities were hypertension (29.8%), psoriatic arthritis (22.2%), and diabetes (17.6%) (table 2) • overall, 42.5% of patients received prior biologic treatment during the 6-month baseline period, of whom 54.0% received tumor necrosis factor inhibitors, 47.6% received ustekinumab, and 3.2% received another il-17a inhibitor (table 2) table 2. comorbidities and treatment history of patients with psoriasis who initiated secukinumab and had 12 months of follow-up characteristic patients with 12-month follow-up (n = 4996) comorbidities, n (%) hypertension 1487 (29.8) psoriatic arthritis 1110 (22.2) diabetes 877 (17.6) hyperlipidemia 751 (15.0) malignancies 633 (12.7) coronary heart disease 125 (2.5) cerebrovascular disease* 70 (1.4) obesity 55 (1.1) rheumatoid arthritis 24 (0.5) treatment history prior biologic treatment preceding secukinumab claim, n (%) tumor necrosis factor inhibitors† 1148 (54.0) ustekinumab 1011 (47.6) il-17a inhibitors‡ 69 (3.2) il, interleukin. * cerebrovascular disease included hemorrhagic stroke and transient ischemic attack. † tumor necrosis factor inhibitors included adalimumab, certolizumab pegol, etanercept, golimumab, and infliximab. ‡ il-17 inhibitors included brodalumab and ixekizumab. clinical characteristics during the baseline period • at baseline, the mean (sd) bsa was 23.0% (22.5%), and 58.1% had severe disease (bsa > 10%) (figure 1a) • the mean (sd) pga score was 2.92 (1.19), and 72.0% had moderate-to-severe involvement (pga score 3-5) (figure 1b) figure 1. categorical clinical outcome measures* in patients who initiated secukinumab and had 12 months of follow-up bsa, body surface area; pga, physician global assessment. * available effectiveness records for pga scores and bsa affected by psoriasis were reported based on the index visit or the visit closest to the index with such values during the 6-month baseline period. 9.3% n = 191 32.6% n = 670 58.1% n = 1196 baseline bsa category baseline categorical bsa (n = 2057) mild (< 3%) moderate (3%-10%) severe (> 10%) mean (sd), 23.0% (22.5%) 4.0% n = 64 9.2% n = 149 14.9% n = 241 44.1% n = 714 18.6% n = 301 9.3% n = 150 baseline pga category baseline categorical pga (n = 1619) clear (0) minimal (1) mild (2) moderate (3) marked (4) severe (5) mean (sd), 2.92 (1.19) a 0 10 20 30 40 50 60 p ro po rt io n of p at ie nt s, % b 0 5 10 15 20 25 30 35 40 45 50 p ro po rt io n of p at ie nt s, % disclosures p. s. yamauchi has served as an investigator for amgen, celgene, dermira, galderma, janssen, leo pharma, eli lilly, medimmune, novartis, pfizer, regeneron, and sandoz and has served as an advisor and/or speaker for abbvie, amgen, baxter, celgene, dermira, galderma, janssen, leo pharma, eli lilly, novartis, pfizer, and regeneron. c.-c. chen and y. ding are employees of iqvia who received consulting fees to conduct this research. r. germino is an employee of novartis pharmaceuticals corporation. acknowledgments support for third-party writing assistance for this poster, furnished by meaghan paganelli, phd, of health interactions, inc, was provided by novartis pharmaceuticals corporation, east hanover, nj. this study was sponsored by novartis pharmaceuticals corporation, east hanover, nj. © 2018 novartis pharmaceuticals corporation. limitations • the mmds database included data captured only from physicians contributing to the emr network (that was then de-identified), and results may not be generalizable to all patients with psoriasis • no continuous health plan enrollment information was captured in the emr database • patients with comorbid psoriatic arthritis or ankylosing spondylitis initiating secukinumab were not excluded from the study population, leading to potential confounding variables conclusion • in this us real-world data analysis of patients with plaque psoriasis, most patients initiating secukinumab had moderate-to-severe disease, > 20% of patients had concomitant psoriatic arthritis, and the most common prior biologic treatment was tumor necrosis factor inhibitors during the 6-month baseline period • overall, these findings are consistent with patient characteristics and severity of psoriasis exhibited in clinical trials and provide additional insight into characteristics and treatment history of patients initiating secukinumab in real-world settings references 1. rachakonda td, et al. j am acad dermatol. 2014;70(3):512-6. 2. lynde cw, et al. j am acad dermatol. 2014;71(1):141-50. 3. langley rg, et al. n engl j med. 2014;371(4):326-38. 4. blauvelt a, et al. br j dermatol. 2015;172(2):484-93. 5. paul c, et al. j eur acad dermatol venereol. 2015;29(6):1082-90. 6. thaci d, et al. j am acad dermatol. 2015;73(3):400-9. 7. armstrong aw, et al. j clin aesthet dermatol. 2016;9(6 suppl 1):s12-6. 8. mease p, et al. ann rheum dis. 2018;77(6):890-7. 9. bagel j, et al. poster presented at: 27th european academy of dermatology and venereology congress; september 12, 2018; paris, france [eposter p1850]. results patient demographics during the baseline period • of 803,036 patients in the mmds database who had a diagnosis of plaque psoriasis during the study period, 4996 patients met the inclusion criteria and had 12 months of follow-up • at baseline, the mean (sd) age was 51.6 (13.7) years, 50.5% were male, and 66.4% were white (table 1) • all us geographic regions were represented: 41.4% were from the south, 21.6% from the west, 20.7% from the midwest, and 16.1% from the northeast regions (table 1) synopsis z seborrheic keratoses (sks) are among the most common benign cutaneous lesions, affecting approximately 84 million individuals in the united states1 z typically, sks do not require removal for medical reasons unless histologic confirmation is required (irritated or inflamed); however, these lesions are often a cosmetic concern to patients, especially if located on the face2 z removal of sks by dermatologists often requires invasive procedures, including cryosurgery, shave excision, electrosurgery, curettage, and laseror light-based treatment2 — given the lack of clinical data supporting the efficacy and safety of these invasive techniques, a substantial unmet need exists for a safe, noninvasive, effective treatment for removal of sks3 z eskata (hydrogen peroxide topical solution 40% [w/w]; hp40; aclaris therapeutics, inc., wayne, pa) is a proprietary, stabilized, noninvasive therapy with demonstrated safety and efficacy in removal of sk lesions of the face, trunk, and extremities, and low risk of skin pigmentation changes or scarring3-5 — hp40 is the first us food and drug administration (fda)-approved topical treatment for individuals with sks that are raised5 objective z to identify segments of consumers with raised facial sks who are interested in a noninvasive treatment (ie, hp40) and describe these consumers in terms of demographics, lifestyle, attitudes, and behaviors methods study design z an online survey was conducted between september 28 and october 13, 2017 among 702 eligible participants aged 35–65 years — the sponsor was not identified to survey participants inclusion criteria z eligible participants were diagnosed with sks by a health care provider or had self-confirmed the presence of sks using the definition and example images provided for the survey z in addition, participants were required to meet the following criteria — bothered by appearance of sks located on the face or hairline (≥3 on a 5-point likert scale [1 = not at all bothered; 2 = slightly bothered; 3 = somewhat bothered; 4 = moderately bothered; 5 = extremely bothered]) — at least somewhat interested in an fda-approved topical treatment to remove sks on the face or hairline — annual income ≥$75,000 and residing in an urban or suburban area exclusion criteria z survey participant or immediate family member was an employee or consultant for any pharmaceutical, advertising, marketing, market research, or public relations company at the time of survey completion sample recruitment quotas z the sample population was estimated to include 140 males (20%) and 560 females (80%), and ≥210 participants (30%) who had visited a dermatologist in the past 2 years z estimated population by age was categorized as 35–39 years (10%), 40–49 years (40%), 50–59 years (40%), and 60–65 years (10%) survey questions z a summary of survey questions is provided in table 1 table 1. number of survey questions included by categorya 1. screening 17 questions 2. demographics and media habits 4 questions 3. lifestyle, personality, skin care attitudes and behaviors, and relationship with a dermatologist 24 questions 4. experience with sks 26 questions 5. profile of a product for treatment of sks 14 questions sks, seborrheic keratoses. athe inclusion of some questions was conditional based on previous participant responses. statistics z categorical data were presented as frequency and percentage and continuous variables were presented as mean (sd) results demographics z a total of 702 survey participants were enrolled; the study population was consistent with the sample recruitment quotas (table 2) table 2. demographics and characteristics of survey participants male 142 (20) age category 35–39 70 (10) 40–49 281 (40) 50–59 281 (40) 60–65 70 (10) visited dermatologist in previous 2 years 290 (41) mean (sd) household income, us dollars 120,566 (24,252) residing in a suburban area 547 (78) values are n (%) unless indicated otherwise. z the racial and ethnic demographics of enrolled survey participants are summarized in figure 1 figure 1. racial and ethnic background of population samplea black, afro-caribbean, african american 10% (n=69) non-hispanic white or euro-american 62% (n=436) hispanic/latin american 12% (n=81) east asian/asian american 13% (n=91) south asian/indian american 1% (n=6) multi-ethnic/racial 3% (n=19) athe sum of the percentages is greater than 100% due to rounding. z survey participants self-reported a fitzpatrick skin type of i or ii (33%), iii (42%), iv (16%), and v or vi (9%) z among survey participants who had visited a dermatologist in the past 2 years, the most common reasons for doing so were routine skin cancer check (66%), removal of noncancerous skin growths, marks, or spots (52%), or to have a suspicious mole or spot checked (47%) z a total of 39% of participants reported that they were previously diagnosed with sks by a health care provider — a total of 99% of participants self-confirmed the presence of spots, growths, or marks similar to sks shown in the images provided aesthetic concerns z a total of 62% of survey participants reported being extremely or very bothered by sks in highly visible areas, including the face and hairline (figure 2) — the mean (sd) score for this question was 3.8 (0.8), between the likert scale scores of 3 (somewhat bothered) and 4 (very bothered) figure 2. question: how bothered are you with the appearance of the sks in your highly visible areas such as the face and hairline?a,b,c 24 38 39 0 10 20 30 40 50 5 extremely bothered 4 very bothered 3 somewhat bothered su rv ey p ar ti ci p an ts , % n=165 n=266 n=271 sks, seborrheic keratoses. aresponses on the likert scale of 1 (not at all bothered) or 2 (slightly bothered) were excluded per the study protocol. bn=702. cthe sum of the percentages is greater than 100% due to rounding. z the primary aesthetic concerns of survey participants were excess body fat, sks on the face or hairline, and wrinkles on the face (figures 3a, 3b) figure 3. question: if you were going to get a treatment to improve your appearance, which issue would you address first, second, and third? (n=702) 2 4 6 8 8 8 9 13 19 23 0 5 10 15 20 25 skin texture sks on body acne or other facial scars uneven skin color/tone or splotches excess fat under chin sagging facial skin unwanted hair on face or body lines or wrinkles on face sks on face or hairline excess fat on body 14 17 22 24 26 31 31 45 45 46 0 5 10 15 20 25 30 35 40 45 50 skin texture acne or other facial scars sks on body excess fat under chin sagging facial skin uneven skin color/tone or splotches unwanted hair on face or body sks on face or hairline lines or wrinkles on face excess fat on body survey participants, % survey participants, % a. ranked first b. ranked in top 3a sks, seborrheic keratoses. aparticipants gave 3 responses each. interest in aesthetic procedures z many survey participants were extremely interested or very interested in skin rejuvenation procedures (48%) or dental aesthetics (43%; figure 4) z a total of 597/702 survey participants (85%) found the blinded product x consisting of highconcentration hydrogen peroxide (hp40) for the in-office treatment of sks by a dermatologist to be extremely appealing or very appealing figure 4. question: how interested are you in getting the following treatments whether you have had them or not?a: participants who responded “extremely interested” or “very interested” (n=702) 10 15 21 25 25 26 36 40 43 48 0 10 20 30 40 50 60 weight loss surgery (gastric bypass or lap-band) breast surgery (reduction/augmentation) liposuction facial aesthetic plastic surgery neurotoxin injections injectable �llers body sculpting/contouring procedures laser or electrolysis hair removal dental aesthetics skin rejuvenation procedures survey participants, % asurvey participants ranked treatments on a 5-point likert scale (5 = extremely interested; 1 = not at all interested). note that the data presented show the combined percentage of patients who responded “extremely interested” or “very interested.” participants could choose more than one response. references 1. bickers dr, et al. j am acad dermatol. 2006;55:490-500. 2. jackson jm, et al. j drugs dermatol. 2015;14:1119-25. 3. baumann ls, et al. j am acad dermatol. 2018 jun 1 [epub ahead of print]. 4. dubois jc, et al. dermatol surg. 2018;44:330-40. 5. eskata [package insert]. wayne, pa: aclaris therapeutics, inc; 2017. acknowledgments this study was sponsored by aclaris therapeutics, inc., wayne, pa. medical writing support was provided by peloton advantage, parsippany, nj, and funded by aclaris therapeutics, inc. disclosures shuai xu, md, msc, reports consulting for aclaris therapeutics. he also reports grant support from pfizer inc, leo pharma, and novartis. stacy wang, pharmd, is an employee of aclaris therapeutics, inc. email address for questions or comments: stevexumd@gmail.com conclusions 1 the majority of survey participants were very bothered or extremely bothered by their sks 2 highly visible sks on the face and hairline were of significant aesthetic concern to patients, and comparable to excess body fat and facial wrinkles 3 a majority of survey participants (85%) expressed that a blinded profile of hp40 was very appealing or extremely appealing, suggesting a strong interest in noninvasive treatment modalities for sk lesions assessing patient concerns regarding seborrheic keratoses on the face: comparison against other cosmetic concerns shuai xu, md, msc,1 stacy wang, pharmd2 1northwestern university feinberg school of medicine, chicago, il; 2aclaris therapeutics, inc., wayne, pa presented at the fall clinical dermatology conference, october 18–21, 2018, las vegas, nevada synopsis objective to compare the efficacy of bimekizumab with ustekinumab and placebo in patients with moderate to severe plaque psoriasis with scalp, palmoplantar, and nail involvement. background • psoriasis is the archetypal th17-driven disease, for which both interleukin (il)-17a and il-17f have emerged as pivotal drivers of inflammation.2 • bimekizumab is a monoclonal igg1 antibody that selectively inhibits il-17f in addition to il-17a.3,4 • in the be vivid phase 3 trial (nct03370133) bimekizumab demonstrated superior clinical efficacy versus ustekinumab and placebo over 16 weeks of treatment (pasi 90: 85.0% versus 49.7% and 4.8%, respectively; p<0.001). this rapid initial response was durable over one year.5 • here, we report efficacy of bimekizumab for patients with scalp, palmoplantar (palms and soles) or nail psoriasis; psoriasis localized in these areas can restrict activities of daily living and negatively impact quality of life, and continues to pose a challenge for both physicians and patients.6 methods • patients were enrolled in be vivid, a randomized, double-blinded, placeboand active comparator (ustekinumab)-controlled study (figure 1). • these post-hoc analyses include patient subsets with scalp investigator’s global assessment (iga) ≥3, palmoplantar (pp)-iga ≥3, or modified nail psoriasis severity index (mnapsi) >10 at baseline. • proportions of patients achieving complete clearance in each region (scalp iga 0, pp-iga 0, mnapsi 0) are reported through week 52. • missing data were imputed using non-responder imputation (nri). results patient population • baseline characteristics for all randomized patients are shown in table 1. scalp, palmoplantar and nail outcomes • among patients with baseline scalp iga ≥3 treated with bimekizumab, scalp response was rapid, with a higher proportion of patients achieving scalp iga 0 at week 16, compared with ustekinumab or placebo; response rates remained high through week 52 (figure 2a). • similar trends were observed in the pp-iga 0 response rates among patients with baseline pp-iga ≥3 (figure 2b). • among those with baseline mnapsi >10, a higher proportion of bimekizumabversus ustekinumab-treated patients achieved nail clearance by week 52 (figure 2c). conclusions bimekizumab demonstrated high levels of efficacy in high-impact areas in patients with moderate to severe plaque psoriasis. complete clearance of scalp, palmoplantar, and nail psoriasis was observed in a higher proportion of patients after 16 weeks of treatment with bimekizumab, compared with ustekinumab or placebo. initial responses were durable through week 52 for bimekizumab-treated patients with scalp and palmoplantar symptoms, and further increased for those with nail symptoms, reflecting the longer timescale required for nail growth. k.a. papp,1 m. lebwohl,2 a.b. gottlieb,2 m. sebastian,3 r. langley,4 y. okubo,5 m. wang,6 c. cioffi,6 f. staelens,7 k. reich8 institutions: 1probity medical research and k papp clinical research, waterloo, ontario, canada; 2icahn school of medicine at mount sinai, new york, new york, usa; 3dermatological practice dr. med. michael sebastian, mahlow, germany; 4dalhousie university, halifax, nova scotia, canada; 5tokyo medical university, tokyo, japan; 6ucb pharma, raleigh, north carolina, usa; 7ucb pharma, braine-l’alleud, belgium; 8center for translational research in inflammatory skin diseases, institute for health services research in dermatology and nursing, university medical center hamburg-eppendorf and skinflammation® center, hamburg, germany bimekizumab for the treatment of moderate to severe plaque psoriasis with scalp, nail and palmoplantar involvement through 52 weeks: post-hoc analysis from the be vivid phase 3 trial references: 1durham l. curr rheumatol reports 2015;17:55; 2fujishima s. arch dermatol res 2010;302:499–505; 3glatt s. br j clin pharmacol 2017;83:991–1001; 4papp ka. j am acad dermatol 2018;79:277–86.e10; 5reich k. aad 2020 oral presentation; 6merola jf. dermatol ther 2018;e12589. author contributions: substantial contributions to study conception/ design, or acquisition/analysis/interpretation of data: kap, ml, abg, ms, rl, yo, mw, cc, fs, kr; drafting of the publication, or revising it critically for important intellectual content: kap, ml, abg, ms, rl, yo, mw, cc, fs, kr; final approval of the publication: kap, ml, abg, ms, rl, yo, mw, cc, fs, kr. author disclosures: kap: honoraria and/or grants from abbvie, akros, amgen, arcutis, astellas, baxalta, boehringer ingelheim, bristol myers squibb, canfite, celgene, coherus, dermira, dow pharma, eli lilly, forward pharma, galderma, genentech, gilead, gsk, janssen, kyowa kirin, leo pharma, medimmune, merck (msd), merck-serono, mitsubishi pharma, moberg pharma, novartis, pfizer, prcl research, regeneron, roche, sanofi genzyme, sun pharma, takeda, ucb pharma and valeant/bausch health; consultant (no compensation) for astrazeneca and meiji seika pharma; ml: employee of mount sinai which receives research funds from abbvie, amgen, arcutis, boehringer ingelheim, dermavant, eli lilly, incyte, janssen, leo pharma, ortho dermatologics, pfizer and ucb pharma; consultant for aditum bio, allergan, almirall, arcutis, avotres, birchbiomed, bmd skincare, boehringer ingelheim, bristol myers squibb, cara therapeutics, castle biosciences, corrona, dermavant, evelo, facilitate international dermatologic education, foundation for research and education in dermatology, inozyme pharma, leo pharma, meiji seika pharma, menlo, mitsubishi pharma, neuroderm, pfizer, promius/dr. reddy’s laboratories, serono, theravance and verrica; abg: honoraria as an advisory board member and consultant for avotres therapeutics, beiersdorf, boehringer ingelheim, bristol myers squibb, eli lilly, incyte, janssen, leo pharma, novartis, sun pharma, ucb pharma and xbiotech (only stock options which she has not used); research/educational grants (paid to mount sinai medical school) from boehringer ingelheim, incyte, janssen, novartis, sun pharma, ucb pharma and xbiotech; ms: received honoraria as an investigator, or received grants and has been an advisor/consultant for abbvie, affibody, almirall, boehringer ingelheim, bristol myers squibb, celgene, dermira, dr. august wolff, dr. reddy’s laboratories, eli lilly, galderma, genentech, gsk, incythe, janssen, leo pharma, medimmune, msd, mundipharma, novartis, pfizer, regeneron and ucb pharma; rl: honoraria from abbvie, amgen, boehringer ingelheim, centocor, eli lilly, janssen, leo pharma, pfizer and valeant/ bausch health for serving as an advisory board member, principal investigator and speaker; yo: research grants from eisai, maruho, shiseido, and torii pharmaceutical; current consulting/advisory board agreements and/or speakers bureau and/or clinical trials from abbvie, amgen, boehringer ingelheim, bristol myers squibb, celgene, eisai, eli lilly, janssen, jimro, kyowa kirin, leo pharma, maruho, mitsubishi pharma, novartis, pfizer, sanofi genzyme, sun pharma, taiho pharma, torii pharmaceutical and ucb pharma; mw, fs: employees of ucb pharma; cc: employee and shareholder of ucb pharma; kr: served as advisor and/or paid speaker for and/or participated in clinical trials sponsored by abbvie, affibody, almirall, amgen, avillion, biogen, boehringer ingelheim, bristol myers squibb, celgene, centocor, covagen, dermira, eli lilly, forward pharma, fresenius medical care, galapagos, gsk, janssen, kyowa kirin, leo pharma, medac, msd, miltenyi biotec, novartis, ocean pharma, pfizer, regeneron, samsung bioepis, sanofi, sun pharma, takeda, ucb pharma, valeant/ bausch health and xenoport. acknowledgements: this study was funded by ucb pharma. we thank the patients and their caregivers in addition to the investigators and their teams who contributed to this study. the authors acknowledge mylene serna, pharmd, ucb pharma, smyrna, ga, usa and susanne wiegratz, msc, ucb pharma, monheim am rhein, germany, for publication coordination; eva cullen, phd, ucb pharma, brussels, belgium, for critical review; joe dixon, phd, costello medical, cambridge, uk for medical writing and editorial support; and the costello medical design team for design support. all costs associated with development of this poster were funded by ucb pharma. previously presented at eadv 2020 virtual congress | october 29–31 table 1 baseline characteristics austekinumab dosing was based on weight: patients ≤100 kg at baseline received one ustekinumab 45 mg injection and one placebo injection, patients >100 kg at baseline received two ustekinumab 45 mg injections. figure 3 bimekizumab treatment examples over 52 weeks scalp iga and mnapsi data shown are total scores for that region in the patient shown. photos are representative of part of that region: back of the scalp and left hand fingers. a) scalp b) nail baseline mnapsi = 22 week 28 mnapsi = 5 week 52 mnapsi = 0 baseline scalp iga = 3 week 8 scalp iga = 1 week 12 scalp iga = 0 week 52 scalp iga = 0 week 2 scalp iga = 2 bimekizumab 320 mg q4w (n=321) ustekinumab 45/90 mg q12w (n=163)a placebo (n=83) age (years), mean ± sd 45.2 ± 14.0 46.0 ± 13.6 49.7 ± 13.6 male, n (%) 229 (71.3) 117 (71.8) 60 (72.3) caucasian, n (%) 237 (73.8) 120 (73.6) 63 (75.9) weight (kg), mean ± sd 88.7 ± 23.1 87.2 ± 21.1 89.1 ± 26.4 duration of pso (years), mean ± sd 16.0 ± 11.6 17.8 ± 11.6 19.7 ± 13.8 scalp iga ≥3, n (%) 235 (73.2) 114 (69.9) 62 (74.7) pp-iga ≥3, n (%) 61 (19.0) 28 (17.2) 14 (16.9) mnapsi >10, n (%) 113 (35.2) 62 (38.0) 30 (36.1) any prior systemic therapy, n (%) 267 (83.2) 132 (81.0) 64 (77.1) prior biologic therapy, n (%) 125 (38.9) 63 (38.7) 33 (39.8) anti-tnf 51 (15.9) 24 (14.7) 16 (19.3) anti-il-17 76 (23.7) 38 (23.3) 18 (21.7) anti-il-23 16 (5.0) 6 (3.7) 5 (6.0) iga: investigator’s global assessment; il: interleukin; mnapsi: modified nail psoriasis severity index; nri: non-responder imputation; pasi: psoriasis area and severity index; pp: palmoplantar; pso: plaque psoriasis; q4w: every 4 weeks; q12w: every 12 weeks; sd: standard deviation; tnf: tumor necrosis factor. figure 1 study design abimekizumab dosing was 320 mg regardless of weight, while ustekinumab dosing was based on weight: patients ≤100 kg at baseline received one ustekinumab 45 mg injection and one placebo injection, patients >100 kg at baseline received two ustekinumab 45 mg injections; bbe bright: nct03598790. enrolled patients were adults with moderate to severe plaque psoriasis (psoriasis area severity index ≥12, ≥10% body surface area affected and iga score ≥3 on a 5 point scale). anominal p<0.001 versus ustekinumab and placebo; bnominal p<0.001 versus ustekinumab; cnominal p=0.087 versus ustekinumab and p<0.001 versus placebo; dnominal p=0.052 versus ustekinumab; enominal p=0.261 versus ustekinumab and p=0.035 versus placebo; fnominal p=0.001 versus ustekinumab. figure 2 scalp, nail, and palmoplantar clearance through week 52 (nri) a) scalp iga 0 in patients with scalp iga ≥3 at baseline b) pp-iga 0 in patients with pp-iga ≥3 at baseline c) mnapsi 0 in patients with mnapsi >10 at baseline p ro p o rt io n o f p a ti e n ts a c h ie vi n g sc a lp i g a 0 36 80 60 40 20 100 0 weeks 32282420161280 404 524844 8.1% 58.8% 75.7%a 51.8% 71.9%b ustekinumab (n=114)bimekizumab (n=235) placebo (n=62) p ro p o rt io n o f p a ti e n ts a c h ie vi n g p p -i g a 0 36 80 60 40 20 100 0 weeks 32282420161280 404 524844 bimekizumab (n=61) ustekinumab (n=28) 67.9% 80.3%d 75.0% 86.9%c 28.6% placebo (n=14) p ro p o rt io n o f p a ti e n ts a c h ie vi n g m n a p s i 0 36 80 60 40 20 100 0 weeks 32282420161280 404 524844 bimekizumab (n=113) ustekinumab (n=62) placebo (n=30) 30.6% 54.0%f 11.3% 18.6%e 3.3% n=321 n=163 n=83 week 16baseline week 52 2–5 weeks bimekizumab 320 mg q4wa bimekizumab 320 mg q4waplacebo ustekinumab 45/90 mg q12wa screening initial treatment period active comparator period maintenance period 20 weeks after last dose: safety follow-up open-label extension study (be bright)b 4:1:2 randomization n=567 presented at winter clinical 2021 virtual congress | january 16–24 • range of 0 to 4 • analysis includes patients scoring 3 (moderate) or 4 (severe) at baseline • score of 0 = clear scalp scalp iga • range of 0 to 4 • analysis includes patients scoring 3 (moderate) or 4 (severe) at baseline • score of 0 = clear hands and feet pp-iga • range of 0 to 130 (0 to 13 per fingernail) • analysis includes patients scoring >10 at baseline • score of 0 = clear nails mnapsi microsoft word cscc.doc skin july 2017 volume i issue i copyright 2017 the national society for cutaneous medicine 1 in-depth reviews development of a metastatic risk model for cutaneous squamous cell carcinoma scott w. fosko mda, melinda b. chu mdb, brandon t. beal mdc, maulik dhandha mdd, eric s. armbrecht phde amayo clinic, department of dermatology, jacksonville, fl boncoderm associates, st. louis, mo ccleveland clinic, department of dermatology, cleveland, oh dsaint louis university, department of dermatology, st. louis, mo esaint louis university, center for outcomes research, st. louis, mo abstract background: cutaneous squamous cell carcinoma (cscc) is the most common cancer capable of metastasis. due to its high incidence and lack of inclusion in national databases it has been difficult to identify high-risk factors associate with metastasis. the development of a cscc metastatic risk model would help physicians identify patients who are at risk for metastasis, and would allow for the initiation of early aggressive management to improve outcomes. aim: explore different statistical approaches to develop a model to predict cscc metastasis that is accurate and reflects routine clinical practice. methods: all csccs diagnosed and treated at saint louis university from january 2010 to march 2012 were included. three statistical approaches were studied: multivariable logistic regression (mlr), pattern classification (pc) and sum score method (ssm). two models using the ssm were created with a different number of factors used to merit assignment to the metastatic cohort: 2 factors (s2) or >2 factors (s2+). for each model, sensitivity (sn), specificity (sp) and positive predictive value (ppv) were calculated. results: sn, sp, and ppv for each model were: mlr: sn 4.3%, sp 97.4%, ppv 16.0%; s2: sn 78.3%, sp 83.7%, ppv 12.5%; s2+: sn 60.9%, sp 96.5% ppv 34.1%; pc: sn 73.9%, sp 95.9%, ppv 34.7%. conclusions: the pc model was the most accurate. the s2+ model had a lower sn, but would be easier to implement as clinicians would only have to sum high-risk factors. regional and/or nodal metastasis is reported to occur in ~3-6% of cutaneous squamous cell carcinomas (csccs).1-3 the task of identifying the rare metastatic case of cscc has been likened to looking for “nodal needles in the cscc haystack.”4 despite the low percentage of metastatic csccs, cscc metastasis is associated with significant abstract introduction skin july 2017 volume i issue i copyright 2017 the national society for cutaneous medicine 2 morbidity and mortality, and represents a significant public health burden due to the prevalence of cscc, with greater than 700,000 new cases diagnosed annually in the united states.1,5 while imaging and sentinel lymph node biopsy (slnb) may assist in the detection of nodal disease, the clinical situations in which they are best utilized are not well defined.4,6 the development of a cscc metastatic risk index that physicians can use in clinic to guide decision making would help to initiate early aggressive management and improve outcomes for high-risk cscc. however, the development of cscc metastatic risk index presents a number of unique challenges: 1) csccs are extremely common, but no centralized cancer registries exist. data collection for csccs is not mandated by the national cancer institute’s survival, epidemiology, end results program (seer) database or the american cancer society as it is for other skin cancers (i.e. melanoma). 2) the high incidence of cscc and low rate of metastasis make it difficult to obtain the detailed data necessary to build a cancer registry. 3) there is currently no standardized definition of high-risk cscc.7-12 4) csccs often have multiple high-risk factors. 5) both tumor and host factors influence metastatic risk, but it has been difficult to determine which combination of high-risk factors contribute most.7-12 the aim of this study is to explore different statistical approaches to develop a model to predict cscc metastasis that is accurate and reflects routine clinical practice. study cohort: this study received institutional review board approval and was conducted at the saint louis university department of dermatology from january 2010 to march 2012. the dataset comprised all csccs diagnosed, managed, or treated by any specialty (e.g., dermatology, otolaryngology, plastic surgery, surgical oncology, radiation oncology, and oncology).the cscc cases were first identified using international classification of diseases 9 th revision codes and then verified by medical and pathology chart review. patient and tumor characteristics including the presence of the american joint committee on cancer (ajcc) and national comprehensive cancer network (nccn) high-risk cscc factors† were recorded.11,12 model development: patient and tumor characteristic variables derived from the nccn high-risk factors were evaluated for inclusion in the statistical models. the nccn high-risk factors are inclusive of the criteria the ajcc uses to stage tumors. five variables were excluded due to rarity (sample prevalence <5%) or absence from routine clinical charting: (1) site of prior radiation or chronic inflammatory process; (2) breslow depth (bd) >2mm, (3) clark level (cl) iv or v; (4) neurological symptoms; and (5) lymphatic or vascular involvement. one variable was excluded due to its subjective definition which increased misclassification bias: (6) poorly defined border. after reviewing the results, 2 † nccn high-risk factors: location/size; poorly defined boarders; recurrent; immunosuppression; sight of prior radiation therapy or chronic inflammatory process; rapidly growing tumor;neurologic symptoms; poorly differentiated; acantholytic,adenosquamous, desmoplastic, or metaplastic subtypes;breslow depth =>2 mm or clark level iv or v; andperineural, lymphatic, or vascular involvement. materials and methods skin july 2017 volume i issue i copyright 2017 the national society for cutaneous medicine 3 additional variables were excluded due to the lack of a significant association (α ≥ 0.1) with the outcome: (7) immunosuppression and (8) acantholytic, adenosquamous, desmoplastic, or metaplastic histologic subtypes. the net result of this process was 5 variables: (1) size by anatomic location; (2) recurrent; (3) rapidly growing; (4) moderate or poorly differentiated histology; (5) perineural invasion (pninv). since it was observed that some anatomic areas, regardless of tumor size, were associated with metastases, a binary summary variable for anatomic location was created. this variable described whether the tumor fulfilled high-risk location by combining nccn areas m and h‡. to further improve model fit the nccn variable for location/size (high-risk areas h, m, & l) was refined using a binary variable with site-specific cut-points determined by an analysis of tumor size stratified by location and metastatic status. to create this variable, the mean diameter of tumors in the metastatic vs. nonmetastatic groups was compared at each anatomic location. after evaluation, it was decided the mean diameter of tumors in the nonmetastatic group plus 2 standard deviations (encompassing 95% of cases) should be used as the benchmark to determine if tumor size in the context of location would be high or low risk. said in another way, size was considered to be a significant factor at a specific anatomic location if the mean size of the tumors in the metastatic cohort was more than 2 standard deviations greater than the mean size of tumors in the nonmetastatic group at that ‡ nccn defines high-risk location/size as any size area h, “mask areas of the face” (central face, eyelids, eyebrows, periorbital, nose, lips [cutaneous and vermilion], chin, mandible, preauricular and postauricular skin/sulci, temple, ear), genitalia, hands, and feet; area m ≥ 10 mm (scalp, forehead, cheeks, neck, and pretibia); and area l ≥ 20 mm (trunk and extremities [excluding pretibial, hands, feet, nail units, and ankles]). site. see table 1. final model variables: after analyses and variable reduction, 6 variables significantly associated with metastasis were included in the models: (1) anatomic location; (2) moderately or poorly differentiated histology; (3) perineurial invasion; (4) rapidly growing; (5) recurrent; (6) size in context of location. model analysis: four models using 3 statistical approaches were studied to determine their ability to accurately predict metastatic status: (1) multivariable logistic regression (mlr); (2) pattern classification (pc); (3) and sum score method (ssm). metastasis was defined as pathologic identification of cscc in a lymph node, the parotid gland, or distant metastasis. sensitivity (sn), specificity (sp) and positive predictive value (ppv) were calculated for each model. multivariable logistic regression: in this model, multiple dependent variables (i.e. risk factors) were assessed and compared to the outcome variable, which is dichotomous (i.e. metastasis or no metastasis).13 sum score method: in this method, a cutoff sum score for group assignment is selected prior to the analysis. two models using the ssm were created with a different number of factors used to merit assignment to the metastatic cohort: 2 factors only (s2) or ≥2 factors (s2+).14 the sum score for each case is calculated by adding up the total number of risk factors present. there was no weighting of the factors§. § for example, a recurrent cscc (1 point recurrence) on the ear (1 point – high-risk location regardless of size) that is rapidly growing (1 point – rapidly growing) is assigned a sum score of 3 points. this tumor would be categorized as nonmetastatic in the s2 model where tumors with only 2 risk factors are designated to be metastatic. in the s2+ model, this tumor would be assigned to the predicted metastatic group. skin july 2017 volume i issue i copyright 2017 the national society for cutaneous medicine 4 pattern classification method: the pc method has been described as a “20 questions” approach where one can intuitively classify a pattern through a sequence of questions. these patterns can be depicted as a decision tree.15 the model attempts to accurately classify the outcome of each case with the least number of decisions and make the simplest decision tree. the study cohort included data on 800 csccs from 585 patients. dermatology diagnosed, managed, and/or treated 93.4% of csccs. there were 23 cases of metastasis (2.9%). most patients (93.7%) contributed 1 or 2 tumors to the data set. eleven patients (1.9%) had greater than 5 tumors and none of these were metastatic. there were 225 tumors located in area l. almost all metastatic cases (95.7%, n=22/23) were located in areas m and h. the metastatic rate for head and neck cscc was 4.2% (n=22/519). metastatic cases were observed on 11 distinct anatomic sites with cheek (n=7) and preauricular area (n=3) being most common. there were 2 metastatic tumors on each of the following sites: scalp, temple, lip and neck. forehead, ear, nose, chin, and arm each had 1 metastatic case. odds ratios and p-values were calculated for variables significant for metastasis: poor or moderate differentiation, anatomic location, size in context of location, rapidly growing, recurrent, and pninv. see table 2. sensitivity, specificity, and positive predictive value: the sn, sp, and ppv for each model are depicted in table 3. the lowest sensitivity was observed in mlr analysis (4.3%); the highest, s2 method (78.3%). the lowest specificity was seen in the s2 method, 83.7%; all other models had specificities > 95%. ppvs ranged from 12.5%-34.7%. mlr and s2 method had similar low ppv (16.0% and 12.5% respectively). the highest ppv was observed in the pc analysis (34.7%), which was closely followed by s2+ (34.1%). anatomic location tumor diameter defined as high-risk by anatomic location face ≥ 2 cm lips > 2.5 cm scalp ≥ 4cm neck > 3 cm extremities > 3 cm table 1. anatomic location and tumor diameter cutoffs defining high-risk risk factor odds ratio p-value poorly or moderately differentiated histology 5.88 .001 anatomic locationa 4.11 .18 size in context of location (see table 1) 4.01 .10 rapidly growing 3.03 .07 recurrent 2.71 .09 perineural invasion 2.03 .28 table 2. final model variables independently associated with metastasis a tumors in areas m and h as defined by the national comprehensive cancer network. results tables skin july 2017 volume i issue i copyright 2017 the national society for cutaneous medicine 5 multivariate logistic regression sum score (s2)a sum score (s2+)b pattern classification sensitivity 4.3% 78.3% 60.9% 73.9% specificity 97.4% 83.7% 96.5% 95.9% positive predictive value 16.0% 12.5% 34.1% 34.7% table 3. sensitivity, specificity, and positive predictive value for each statistical model asum score (2): sum score method performed where tumors with any 2 risk factors were assigned to metastatic cohort. bsum score (2+): sum score method performed where tumors with 2 or more risk factors were assigned to metastatic cohort. in this analysis, we sought to explore different statistical models, mlr, ssm, and pc, and their sn, sp, and ppv in detecting metastasis. the pc model had the highest accuracy: sn 73.9%, sp 95.9%, and ppv 34.7%. also of note was the finding that 95.7% (n=22/23) of metastatic cscc were located on the head and neck. that the pc model had the highest values for sn, sp, and ppv when examined in aggregate suggests both the combination and the additive effect of risk factors contribute to cscc metastasis. while statistically the pattern classification method might appear complex and inaccessible, the approach is fundamentally similar to the way physicians are trained to diagnosis and manage diseases. all available data is assimilated and considered with certain data weighted more or less. for example, a 1 cm moderately-differentiated cscc with pninv on the forearm is considered to have a lower metastatic risk than a 2.5 cm well-differentiated tumor on the ear. both tumors exhibit 2 risk factors in our models, but the tumor on the ear would prompt higher concern than the cscc on the arm. when developing a prognostic model, ease of use in clinical practice must be considered. while the sn of s2+ is lower than pc, the simplistic s2+ approach may be more feasible to implement (the user just has to calculate a score based on predefined variables). in this model, any 3 combinations of risk factors in table 2 would be concerning for metastasis. the most well-known use of the ssm might be the chads2 score which measures stroke risk in patients with atrial fibrillation.16 in this study we identified several variables independently associated with cscc metastasis which are relevant to clinical practice: poorly or moderately differentiated histology, anatomic location (areas h and m), size in context of location (table 1), rapidly growing, recurrent, and pninv. poorly or moderately differentiated histology, anatomic location (areas h and m), and size in context of location (table 1) all had odds ratios greater than 4 and are also commonly noted in other studies as significant high-risk factors for metastasis. 8-12,17 the nccn guidelines represent the broadest and most comprehensive definition of high risk cscc factors currently available.12 and while the ajcc has attempted to refine cscc high-risk factors for staging purposes and prognostic value, they have not been successful.7-9 jambusaria-pahlajani et al8 developed an alternative staging system for cscc which provides greater ability to stratify high-risk csccs and improves prognostic accuracy.9 their alternative staging system uses 4 high-risk factors: poor differentiation, discussion skin copyright 2017 the national society for cutaneous medicine 6 pninv, tumor diameter ≥ 2 cm, and invasion beyond subcutaneous fat. in another recent study, thompson et al.10 performed a meta analysis of 23,421 csccs and found invasion beyond subcutaneous fat, bd > 2mm, diameter > 2 cm, poor differentiation, pninv, immunosuppression, and location on the temple, ear, and lip to be significant risk factors for metastasis. lastly, peat et al.17 performed a risk stratification analysis for metastasis from cscc and found poor and moderate differentiation, pninv and lymphovascular invasion, diameter ≥ 2 cm, and cl v to be important variables for metastasis. thought the aims of these studies and ours were all slightly different, there was significant overlap between these studies high-risk factors for metastasis and ours poor differentiation, pninv, and location/size. while the prevalence rate for cscc metastasis of 2.9% in this study is consistent with published studies1-3, the low prevalence negatively impacted the ppv in all models, and did not allow any model to near or even exceed a ppv of 50%. the pc model had the highest ppv at 34.7%. this is a universal factor that makes identifying high-risk and metastatic cscc so difficult, the extremely high incidence of cscc and the extremely low prevalence of cscc metastasis. in the southern half of the united states metastatic cscc is estimated to have a higher mortality than melanoma due to the high incidence of cscc and despite the low prevalence of cscc metastasis1; thus, demonstrating the importance of identifying these high-risk tumors early. while our results are informative, the study has several limitations: 1) this is a single institution study, 2) we were not able to evaluate the clinical importance of bd or cl due to the absence of the routine collection of this data in clinical practice. in our experience, bd and cl are not routinely recorded as it would be impractical to have dermatopathologists report bd or cl for every cscc, thus while this is a limitation, it is a reflection of clinical practice and 3) there were no standard criteria for which patients received slnbs which could impact rates of metastasis within this population. conflict of interest disclosures: none. funding: none. corresponding author: brandon t. beal, md department of dermatology dermatology & plastic surgery institute cleveland clinic 9500 euclid ave / a61 cleveland, oh 44195 phone: (216) 444-5772 fax: (216) 636-0435 e-mail: bealb@ccf.org references: 1. karia ps, han j, schmults cd. cutaneous squamous cell carcinoma: estimated incidence of disease, nodal metastasis, and deaths from disease in the united states, 2012. j am acad dermatol. 2013;68(6):957-966. 2. breuninger h, eigentler t, bootz f, hauschild a, et al. brief s2k guidelines-cutaneous squamous cell carcinoma. j dtsch dermatol ges. 2013;11 suppl 3:37-45, 39-47. 3. czarnecki d, staples m, mar a, giles g, meehan c. metastases from squamous cell carcinoma of the skin in southern australia. dermatology. 1994;189(1):52-54. 4. karia ps, schmults cd. screening for nodal metastasis and its challenges: nodal needles in the scc haystack. jama dermatol. 2014;150(1):16 17. 5. donaldson mr, coldiron bm. no end in sight: the skin cancer epidemic continues. semin cutan med surg. 2011;30(1):3-5. 6. ruiz es, karia ps, morgan fc, schmults cd. the positive impact of radiologic imaging on high-stage cutaneous squamous cell carcinoma management. j am acad dermatol. 2017 feb;76(2):217-225. july 2017 volume i issue i skin copyright 2017 the national society for cutaneous medicine 7 7. chu md, slutsky jb, dhandha mm, beal bt et al. evauation of the definitions of "high-risk" cutaneous squamous cell carcinoma using the america joint committee on cancer staging criteria and national comprehenisve cancer network guidelines. j skin cancer. 2014;154340. 8. jambusaria-pahlajani a, kanetsky pa, karia ps, hwang wt et al. evaluation of ajcc tumor staging for cutaneous squamous cell carcinoma and a proposed aternative tumor staing system. jama dermatol. 2013 apr;149(4):402-10. 9. karia ps, jambusaria-pahlajani a, harrington dp, murphy gf, et al. evaluation of american joint committee on cancer, international union agaist cancer, and brigham and women's hospital tumor staging for cutaneous squamous cell carcinoma. j clin oncol. 2014 feb 1;32(4):327-334. 10. thompson ak, kelley bf, prokop lj, murad mh, baum cl. risk factors for cutaneous squamous cell carcinoma recurrence, metastasis, and disease-specific death: a systematic review and meta-analysis. jama dermatol. 2016;152(4):419 428. 11. edge sb, byrd dr, compton cc, et al., editors. ajcc cancer staging manual. 7th edition. new york, ny, usa: springer; 2010. cutaneous squamous cell carcinoma and other cutaneous carcinomas; pp. 301–314. 12. national comprehensive cancer network. squamous cell skin cancer (version 1.2017). available from: url: http://www.nccn.org/professionals/physician_gls/pd f/ squamous.pdf. accessed april 2017. 13. hidalgo b, goodman m. multivariate or multivariable regression? am j public health. 2013;103(1):39-40. 14. distefano c zm, mindrila d. understanding and using factor scores: considerations for the applied researcher practical assessment research & evaluation. 2014. 15. ro. d. decision trees. pattern classification new york, ny: wiley & sons; 2004:394-396. 16. gage bf, waterman ad, shannon w, boechler m, et al. validation of clinical classification schemes for predicting stroke: results from the national registry of atrial fibrillation. jama. 2001;285(22):2864-2870. 17. peat b, insull p, ayers r. risk stratification for metastasis from cutaneous squamous cell carcinoma of the head and neck. anz j surg. 2012;82(4):230-233. july 2017 volume i issue i skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 307 brief article cutaneous endometriosis: a case report alan wong, bs1; stefanie altmann, do2; karthik krishnamurthy, do2 1lake erie college of osteopathic medicine, bradenton, fl 2orange park medical center, division of dermatology, orange park, fl cutaneous endometriosis (cem) is defined as the presence of endometrial glands and/or stroma in the dermis or subcutis.1,2 cem primarily affects women of reproductive age and represents 0.5-1% of all ectopic endometriosis.2,3 cem can be classified as primary or secondary, with primary cem accounting for less than 30% of all cases.1 the cause of primary cem is unclear and occurs spontaneously. although risk factors for developing primary cem are not clearly defined, age and hormone levels likely play a role since a majority of affected individuals are premenopausal.1,2 secondary cem, also called scar endometriosis, is believed to occur due to seeding/iatrogenic implantation of endometrial tissue into the skin during abdominopelvic surgeries.1,2 clinically, cem presents as a firm papule or nodule averaging 2 cm in diameter. lesions may be blue, violaceous, red, brown or skincolored.1 patients with cem usually experience pain, swelling, itching, or bleeding from affected areas of the skin in a cyclical pattern related to the menstrual cycle. the most common location for both primary and secondary cem is the umbilicus.1,2 other locations for cem include abdominopelvic scars, episiotomy wounds, and upper extremities.2 diagnosis must be confirmed via histopathologic examination, and treatment options include surgical excision or hormonal therapy.1 since symptoms of cem are limited to the skin and not all women have associated pelvic endometriosis,1,2 dermatologists may be the first clinicians that see patients with cem. as such, it is important for abstract cutaneous endometriosis (cem) is a rare disease characterized by endometrial glands and/or stroma in the skin. lesions present as a firm papule or nodule and can be blue, violaceous, red, brown or skin-colored. patients frequently report cyclical tenderness, swelling and bleeding at the site of the lesion related to their menstrual cycle. cem presents a diagnostic challenge as lesions are commonly mistaken for a keloid, dermatofibroma, dermatofibrosarcoma protuberans, melanoma or cutaneous metastasis of cancer (e.g., sister mary joseph nodule). a biopsy must be taken to rule out malignancy and treatments include surgical excision and hormonal agents. to our knowledge, just over 100 cases have been reported in the literature. herein we highlight a case of cem in a 43-year-old female that presented to dermatology after being overlooked on prior work-up with obstetrics and gynecology. this case highlights the need for dermatologists to be familiar with cem, as we may be the first clinicians these patients present to for painful cutaneous lesions. introduction skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 308 dermatologists to be able to recognize the characteristic clinical and histologic features of cem and obtain a thorough history, physical and workup to aid in the diagnosis and guide management. a 43-year-old female presented with a bluish, 1.5 cm fluctuant and tender nodule on the umbilicus that had been present for approximately six months (figure 1). upon further questioning, she reported that the lesion was more painful with menstruation and occasionally bled. she also reported a distant surgical history of cesarean section, laparoscopic appendectomy, and umbilical repair. she was evaluated by obstetrics and gynecology for pelvic pain two months prior, and was diagnosed with pelvic endometriosis; however, the umbilical nodule was not evaluated at that time. a 4mm punch biopsy was performed in our clinic for further evaluation. histopathology showed endometrial glands and stroma with extravasated red blood cells, consistent with cem (figures 2, 3). no signs of atypia or malignancy were observed. due to the patient’s history of cesarean section, the lesion was classified as secondary cem. the patient was referred to obstetrics and gynecology for surgical excision. cem presents a diagnostic challenge as lesions are commonly mistaken for keloid, dermatofibroma, dermatofibrosarcoma protuberans, melanoma or cutaneous metastasis of cancer (e.g., sister mary joseph nodule).1-5 as studies have shown that 14% of women with cem in gynecological scars have associated pelvic figure 1. solitary 1.5-cm bluish nodule at the umbilicus figure 2. histopathology showing endometrial glands lined with columnar epithelium, endometrial stroma with dense spindle cells shaped cells, and extravasated red blood cells (h&e, 2x) endometriosis,4 a majority of patients with cem may present with cutaneous manifestations alone. thus, dermatologists may be the first clinicians these patients elect to see, and it is crucial to be able to recognize the salient features of cem. case presentation discussion skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 309 the cyclical symptoms associated with cem, is one of the most important clinical features. the pain, swelling and/or bleeding usually correspond with the patient’s menstrual cycle and should increase suspicion for cem. obtaining a thorough surgical history is also key as it will help classify the lesion as primary or secondary cem. patients should also be offered a referral to gynecology if they desire to be evaluated for pelvic endometriosis or have symptoms such as dysmenorrhea or pelvic pain.1,2 figure 3. histopathology showing endometrial glands lined with columnar epithelium, endometrial stroma with dense spindle cells shaped cells, and extravasated red blood cells (h&e, 20x) diagnosis of cem can be made with either punch or excisional biopsy.1-3 an abdominal ultrasound should be obtained prior to the biopsy if there is a high suspicion for uterocutaneous fistula.1,2 in our case, the lesion was well circumscribed with no palpable deep component, and outside any surgical scars, therefore pre-procedure imaging was not obtained prior to biopsy. of note, excisional biopsy with 1 cm margins is both diagnostic and curative in cases of scar endometriosis.4 however, some authors prefer to use 2 mm margins, especially since the risk of recurrence in relation to surgical margins has not been officially determined.5 histologically, cem is characterized by three features: endometrial glands composed of columnar epithelium, endometrial stroma characterized by dense spindle shaped cells, and hemorrhage. the tissue must be evaluated for atypia/dysplasia to rule out malignancy. interestingly, lesions may have marked decidual changes and can mimic a malignant process.6 although it is often not performed in practice, immunohistochemistry can help confirm the diagnosis; endometrial glands frequently stain positive for cd7, estrogen receptors and progesterone receptors.3 the stroma is often strongly positive for cd10.3 notably, cd10 is particularly helpful if there is a paucity of glands and abundance of stroma in lesions.3 also, since cd7 stains positively in > 95% of primary endometrial adenoid tumors, it can help distinguish cem from primary metastatic tumors.3 finally, the patient should be educated on surgical and hormonal treatment options. surgical excision with wide margins is considered first line treatment.1,2 perioperative recommendations vary and include performing surgery at the end of the menstrual cycle, as lesions are generally smaller. adjuvant treatment with preoperative hormonal agents may help to shrink the lesion and reduce symptoms. additionally, postoperative use of hormonal agents to prevent recurrence could be considered.1 prognosis is favorable as recurrence following wide excision is rare.1-5 hormonal therapies include leuprolide, danazol and oral contraceptives, and can be used as monotherapy for patients who do not wish to undergo surgery.1,2 although hormonal treatments can provide symptomatic relief, they are associated with numerous side effects and symptoms of skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 310 cem can return once therapy is discontinued.1 in the event patients opt for hormonal therapy alone, regular surveillance with histopathology should be considered as there have been reports of malignant transformation in the literature.1 overall, malignant transformation of cem is rare and is estimated to occur in 0.3-1% of secondary cem cases.7 associated risk factors include advanced age, postmenopausal status, delayed or incomplete excision, clinical recurrence, and endometriotic lesions > 9 cm in diameter.7 recognizing cem is important for dermatologists as we may be the first clinicians to see these patients. cem presents as a firm, blue/violaceous/brown/red/skin-colored papule or nodule. cyclical pain, swelling or bleeding relating to the menstrual cycle should arise suspicion in favor of cem, particularly if the lesion originated at a surgical scar from an abdominopelvic procedure. cem requires a biopsy to ensure the correct diagnosis and to rule out malignancy. definitive treatment is surgical excision with wide margins and recurrence after surgery is rare. conflict of interest disclosures: none funding: this research was supported in part by hca healthcare or an hca healthcare affiliated entity. the views expressed in this publication represent those of the authors and do not necessarily represent the official views of hca healthcare or any of its affiliated entities. corresponding author: stefanie altmann, do division of dermatology orange park medical center 2001 kingsley ave orange park, fl 32073 phone: 407-414-6556 email: stefanie.altmann@hcahealthcare.com references: 1. sharma a, apostol r. cutaneous endometriosis. in: statpearls. treasure island (fl): statpearls publishing; august 8, 2020. 2. raffi l, suresh r, mccalmont th, twigg ar. cutaneous endometriosis. int j womens dermatol. 2019;5(5):384-386. published 2019 jul 2. doi:10.1016/j.ijwd.2019.06.025 3. ojong o, susa j, weiss e. a solitary brown nodule on the umbilicus. jaad case rep. 2020;6(10):1024-1026. published 2020 aug 14. doi:10.1016/j.jdcr.2020.08.010 4. tatli f, gozeneli o, uyanikoglu h, et al. the clinical characteristics and surgical approach of scar endometriosis: a case series of 14 women. bosn j basic med sci. 2018;18(3):275-278. published 2018 aug 1. doi:10.17305/bjbms.2018.2659 5. din ah, verjee ls, griffiths ma. cutaneous endometriosis: a plastic surgery perspective. j plast reconstr aesthet surg. 2013;66(1):129130. doi:10.1016/j.bjps.2012.05.012 6. declerck bk, post md, wisell ja. cutaneous decidualized endometriosis in a nonpregnant female: a potential pseudomalignancy. am j dermatopathol. 2012;34(5):541-543. doi:10.1097/dad.0b013e3182473172 7. fargas fàbregas f, cusidó guimferrer m, tresserra casas f, baulies caballero s, fábregas xauradó r. malignant transformation of abdominal wall endometriosis with lymph node metastasis: case report and review of literature. gynecol oncol case rep. 2014;8:10-13. published 2014 jan 5. doi:10.1016/j.gynor.2013.12.003 conclusion powerpoint presentation background results discussion a randomized, investigator-blinded study to compare the efficacy and tolerance of a 650-microsecond, 1064-nm yag laser to a 308-nm excimer laser for the treatment of mild-to-moderate psoriasis vulgaris mark s. nestor, m.d., ph.d.1,2, daniel fischer, d.o., m.s.1, david arnold, d.o.1, haowei han, d.o.1, anita gade, d.o.1, francesca ceci, m.d.1, austin dunn, d.o.1 , alec lawson, b.a.1 1center for clinical and cosmetic research, 2university of miami miller school of medicine phototherapy is a safe and effective treatment option for psoriasis and does not incur the side effects of systemic medications.1 the 308-nm excimer laser is considered firstline phototherapy for plaque psoriasis.1 the excimer laser is able to treat psoriatic lesions with high doses of monochromatic radiation while sparing unaffected skin.1 the 650-microsecond 1064-nm nd: yag laser was introduced in 2009 by khatri and colleagues and is also fda approved for the treatment of psoriasis. the advantage of the 650-microsecond laser is that treatment does not require cooling or anesthesia because the pulse duration is shorter than or equal to the thermal relaxation time of the therapeutic target. this feature minimizes scarring, pigmentary changes, thermal damage to surrounding tissues, and discomfort during or after treatment.2 objective the primary objective of this study was to compare the ability of the 650microsecond, 1064-nm pulsed yag laser (lightpod neo®, aerolase corp., tarrytown, ny) to clear psoriatic plaques with that of the 308-nm excimer laser (xtrac velocity 400®, photomedex, inc., montgomeryville, pa). methods subjects: eligible subjects (n=15) were healthy and included 11 males and 4 females aged 54.3 ± 11.7 (mean ± sd) years. study design: psoriatic plaques were randomized to receive one of the two laser treatments. laser therapy was administered with either the 650-microsecond laser on one side or the 308-nm excimer laser on the other side. a non-blinded individual treated each psoriatic plaque according to the randomization scheme. subjects made up to 15 treatment visits, twice weekly or fewer if full clearance was achieved. treatment parameters: the 650-microsecond laser settings were the following: lens type 5 to 6 mm, energy mode 7 to 8, and pulse width 650 microseconds. fluence ranged from 24 to 41 j/cm2. each subject received multiple passes per treatment session. for the excimer laser, median dose (fluence) ranged from 0.60 to 0.96 j/cm2 and median body surface area treated ranged from 800 to 1410 cm2. multiple passes were not required. assessments: measured outcomes include the body surface area (bsa) involvement at baseline and the end-of-study visits, subject reported itch by numerical rating scale (nrs), the modified psoriasis area and severity index (mpasi) and local skin reaction (lsr). the efficacy of the 650-microsecond laser has been shown to be equivalent to that of the excimer laser for the treatment of mild to moderate psoriasis vulgaris of the arms and legs (figures 2, and 3). however the moa is different as 650-microsecond laser energy deeply penetrates the plaque to target the excessive micro capillaries feeding plaque growth. differences were not significant for redness, thickness, scaliness, mpasi scores for arms and legs, and overall mpasi scores. as shown in figure 1, the median overall mpasi scores for both lasers were identical for all except treatment 4. as expected, the values decreased rapidly until visit 10 when they leveled off at 1.3 and decreased to 1.2 at the end of the study. tolerance of both laser treatments was excellent. the 650-microsecond nd:yag 1064nm laser offers unique features not available in other devices. since the pulse duration is shorter than the thermal relaxation time of both the skin and blood vessels, the therapeutic target is heated more rapidly than the rate heat is conducted to the surrounding skin, thus reducing damage and lowering the risk of pigmentary alterations.3 additional advantage of the 650-microsecond laser is that it allows safe and effective treatment of other widespread skin conditions such as active acne3, onychomycosis4, rosacea2, hyperpigmentation and lhr5 etc. twelve subjects (80%) completed the study. one subject withdrew because of a change in work schedule that interfered with study visits. two other subjects were lost to follow-up. body surface area: the median bsa at baseline (n=15) was 2.00, ranging from 2.0 to 4.0. at the end of the study (n=12), the median bsa was 2.25 and values ranged from 2.0 to 4.0. the median bsa at the end of study did not differ significantly from baseline. mpasi scores: differences between the 650-microsecond and excimer lasers were not significant for redness, thickness, scaliness, or mpasi scores. overall mpasi scores for 650-microsecond vs. excimer lasers throughout the study period are shown in the figure 1. local skin reactions: median reaction scores were identical on both sides of the body. median reaction scores were zero for each reaction parameter. maximum values ranged from 0 to 2 for erosion/ulceration and erythema and from 0 to 3 for scaling. subject reported itch by numerical rating scale: median values were identical for both laser. values varied from 2 to 4 during the initial visits and decreased to 2 by the end of the study. the median itch score at the end of the study was significantly lower than the baseline value (p = 0.0156). 2.8 2.3 1.6 1.3 1.3 1.3 1.2 2.8 2.5 1.6 1.3 1.3 1.3 1.2 0 0.5 1 1.5 2 2.5 3 0 4 7 10 14 15 eos m pa s i s co re no. of treatments overall mpasi score aerolase excimer references conclusion the strength of the present study is its comparison with the excimer laser, the current first-line phototherapy for the treatment of mild-to-moderate psoriasis vulgaris. the efficacy and tolerance of the 650-microsecond laser has been shown to be equivalent to that of the excimer laser for the treatment of mild to moderate psoriasis vulgaris of the arms and legs and treatment-related adverse events were not observed. limitations are the small number of patients and the short follow-up time. the encouraging results justify additional studies with more patients and longer follow-up time. 1. zhang p, wu mx. a clinical review of phototherapy for psoriasis. lasers med sci. 2018;33:173-180. 2. rose ae, goldberg dj. successful treatment of facial telangiectasias using a micropulse 1,064-nm neodymium-doped yttrium aluminum garnet laser. dermatol surg 2013;39:1062-1066. 3. gold mh, goldberg dj, nestor ms. current treatments of acne: medications, lights, lasers, and a novel 650μs 1064-nm nd: yag laser. j cosmet dermatol. 2017;16:303-318. 4. hochman lg. laser treatment of onychomycosis using a novel 0.65-millisecond pulsed nd: yag 1064-nm laser. j cosmet laser ther 2011;13:2-5 5. roberts we, henry m, burgess c, et al. laser treatment of skin of color for medical and aesthetic uses with a new 650-microsecond nd:yag 1064nm laser. j drugs dermatol. 2019;18:s135-s137 figure 3. left knee of a 65-year-old black male before(left) and after (right) 15 treatments (24 jcm2, multiple passes) with the 650-microsecond, 1064-nm pulsed yag laser figure 1. overall mpasi scores for 650-microsecond vs. excimer lasers after the indicated treatments. eos = end of study. figure 2. left hand of a 60-year-old white male before (left) and after (right) 15 treatments (28 j/cm2, multiple passes) with the 650-microsecond, 1064-nm pulsed yag laser. poster presented at the 36th fall clinical dermatology conference | las vegas, nv | october 12-15, 2017 patient-reported outcomes from two randomized, double-blind, vehicle-controlled phase 3 trials in axillary hyperhidrosis (atmos-1 & atmos-2) david m. pariser,1 adelaide a. hebert,2 janice drew,3 john quiring4, dee anna glaser5 1eastern virginia medical school and virginia clinical research, inc., norfolk, va; 2uthealth mcgovern medical school at houston, houston, tx; 3dermira, inc., menlo park, ca; 4qst consultations, allendale, mi; 5saint louis university, st. louis, mo introduction • hyperhidrosis affects an estimated 4.8% of the us population, or approximately 15.3 million people, and negative psychological consequences are experienced by approximately 75% of patients with the disorder1 • the prevalence of anxiety and depression is over 3.5 times greater in people with hyperhidrosis than in those without it, and there is a positive correlation between the severity of hyperhidrosis and rates of anxiety and depression2 • topical glycopyrronium tosylate (gt; formerly drm04) is a cholinergic receptor antagonist being developed for the treatment of primary axillary hyperhidrosis in patients ≥9 years of age • gt has been assessed in 2 replicate randomized clinical trials (atmos-1 [sites in the us and germany] and atmos‑2 [us sites only]); the primary efficacy and safety results of these studies have been previously reported3 • patient‑reported outcomes (pros) from these pivotal trials were also assessed using the 4‑item axillary sweating daily diary (asdd),4 6 weekly impact items, and the single‑item patient global impression of change (pgic) that were developed according to current regulatory standards – the asdd/asdd‑c axillary sweating severity item (item 2) was specifically developed for use as an endpoint in clinical trials in support of approval and labeling (also as a useful clinical parameter) objective • to evaluate changes in patient‑reported outcomes after 4 weeks of treatment with gt compared with vehicle in atmos‑1 and atmos‑2 methods atmos-1 and atmos-2 study design • atmos‑1 (drm04‑hh04; nct02530281) and atmos‑2 (drm04‑hh05; nct02530294) were parallel‑group, 4‑week, double‑blind, phase 3 clinical trials in which patients with primary axillary hyperhidrosis were randomized (2:1) to gt or vehicle (figure 1) – coprimary endpoints included asdd axillary sweating severity item (item 2) responder rate (defined as ≥4‑point improvement from baseline) at week 4 and mean absolute change from baseline in gravimetrically‑measured sweat production at week 4 • eligible patients were ≥9 years of age (patients <16 years were only recruited at us sites) and had primary axillary hyperhidrosis for ≥6 months, with gravimetrically‑measured sweat production of ≥50 mg/5 min in each axilla, asdd item 2 score ≥4, and hyperhidrosis disease severity scale (hdss) grade 3 or 4 • patients were excluded for history of a condition that could cause secondary hyperhidrosis; prior surgical procedure or treatment with a medical device for axillary hyperhidrosis; treatment with iontophoresis within 4 weeks or treatment with botulinum toxin for axillary hyperhidrosis within 1 year; axillary use of nonprescription antiperspirants within 1 week or prescription antiperspirants within 2 weeks; new or modified psychotherapeutic medication regimen within 2 weeks; treatment with medications having systemic anticholinergic activity, centrally acting alpha‑2 adrenergic agonists, or beta‑blockers within 4 weeks unless dose had been stable ≥4 months and was not expected to change; and/or conditions that could be exacerbated by study medication figure 1. study design week 0 week 4 atmos-1 and atmos-2 target recruitment: 330 patients randomized 2:1 gt vehicle patient-reported outcomes • axillary hyperhidrosis patient measures (ahpm) – the asdd consists of 4 items and was used for patients ≥16 years; patients <16 years of age completed a modified, 2‑item version of the asdd, the asdd‑c (table 1) – patients ≥16 years were additionally asked to complete 6 weekly impact items and a single-item patient global impression of change (pgic) (table 1) • mean changes from baseline were summarized by descriptive statistics in the intent‑to‑treat (itt) population (all randomized subjects who were dispensed study drug) – for asdd item 2 (all patients) and asdd items related to the impact and bother of axillary sweating (items 3 and 4, respectively; patients ≥16 years of age), baseline was defined as the average of ≥4 days of data in the most recent 7 days prior to randomization – for the weekly impact items (patients ≥16 years of age), baseline was defined as the last available record prior to day 1 – as the pgic was only administered at the end of study treatment, there was no baseline value • missing values for asdd items 2 through 4 were not imputed; for weekly impact items, the last observation carried forward (locf) approach was used to impute missing values • an additional analysis was performed to assess the percent improvement from baseline to week 4 in asdd item 2, 3, and 4 scores table 1. axillary hyperhidrosis patient measures (ahpm)a axillary sweating daily diary (asdd)b instructions: the questions in the diary are designed to measure the severity and impact of any underarm sweating you have experienced within the previous 24 hour period, including nighttime hours. while you may also experience sweating in other locations on your body, please be sure to think only about your underarm sweating when answering these questions. please complete the diary each evening before you go to sleep. item 1 [gatekeeper] during the past 24 hours, did you have any underarm sweating? yes/no when item 1 is answered “no,” item 2 is skipped and scored as zero item 2 during the past 24 hours, how would you rate your underarm sweating at its worst? 0 (no sweating at all) to 10 (worst possible sweating) item 3 during the past 24 hours, to what extent did your underarm sweating impact your activities? 0 (not at all), 1 (a little bit), 2 (a moderate amount), 3 (a great deal), 4 (an extreme amount) item 4 during the past 24 hours, how bothered were you by your underarm sweating? 0 (not at all bothered), 1 (a little bothered), 2 (moderately bothered), 3 (very bothered), 4 (extremely bothered) axillary sweating daily diary-children (asdd-c)c instructions: these questions measure how bad your underarm sweating was last night and today. please think only about your underarm sweating when answering these questions. please complete these questions each night before you go to sleep. item 1 [gatekeeper] thinking about last night and today, did you have any underarm sweating? yes/no when item 1 is answered “no,” item 2 is skipped and scored as zero item 2 thinking about last night and today, how bad was your underarm sweating? 0 (no sweating at all) to 10 (worst possible sweating) weekly impact itemsb instructions: please respond “yes” or “no” to each of the following questions. a. during the past 7 days, did you ever have to change your shirt during the day because of your underarm sweating? yes/ no b. during the past 7 days, did you ever have to take more than 1 shower or bath a day because of your underarm sweating? yes/ no c. during the past 7 days, did you ever feel less confident in yourself because of your underarm sweating? yes/ no d. during the past 7 days, did you ever feel embarrassed by your underarm sweating? yes/ no e. during the past 7 days, did you ever avoid interactions with other people because of your underarm sweating? yes/ no f. during the past 7 days, did your underarm sweating ever keep you from doing an activity you wanted or needed to do? yes/ no patient global impression of change (pgic) itemb overall, how would you rate your underarm sweating now as compared to before starting the study treatment? 1 (much better), 2 (moderately better), 3 (a little better), 4 (no difference), 5 (a little worse), 6 (moderately worse), 7 (much worse) aasdd/asdd-c item 2 is a validated pro measure bfor use in patients ≥16 years of age cfor use in patients ≥9 to < 16 years of age results • a total of 697 patients were randomized and were asked asdd/asdd‑c items 1 and 2 on a daily basis; 665 patients were ≥16 years of age and were asked asdd items related to the impact and burden of sweating on a daily basis (items 3 and 4, respectively), the weekly impact items on a weekly basis, and the pgic at end of treatment • demographic and baseline disease characteristics from the primary studies are presented in table 2 table 2. demographics and baseline disease characteristics atmos-1 atmos-2 vehicle (n=115) gt (n=229) vehicle (n=119) gt (n=234) demographics age (years), mean ± sd 34.0 ± 13.1 32.1 ± 11.2 32.8 ± 11.2 32.6 ± 10.9 age group, n (%) <16 years ≥16 years 6 ( 5.2) 109 (94.8) 5 ( 2.2) 224 (97.8) 10 ( 8.4) 109 (91.6) 11 ( 4.7) 223 (95.3) male, n (%) 55 (47.8) 99 (43.2) 59 (49.6) 113 (48.3) white, n (%) 94 (81.7) 182 (79.5) 102 (85.7) 192 (82.1) bmi (kg/m2), mean ± sd 27.2 ± 4.9 27.6 ± 5.8 28.4 ± 5.5 27.3 ± 5.0 baseline disease characteristics, mean ± sd years with primary axillary hyperhidrosis 16.0 ± 11.4 13.7 ± 10.4 15.9 ± 9.9 16.9 ± 11.1 sweat production (mg/5 min)a 170.3 ± 164.2 182.9 ± 266.9 181.9 ± 160.1 162.3 ± 149.5 asdd/asdd-c item 2 (severity) 7.1 ± 1.7 7.3 ± 1.6 7.2 ± 1.6 7.3 ± 1.6 asdd item 3 (impact)b 2.2 ± 0.9 2.4 ± 0.9 2.3 ± 1.0 2.5 ± 0.8 asdd item 4 (burden)b 2.4 ± 0.9 2.6 ± 0.8 2.5 ± 0.9 2.7 ± 0.9 agravimetrically-measured bmean baseline scores for asdd items 3 and 4 are based on all patients in the itt populations of atmos‑1 and atmos‑2 ≥16 years of age only baseline scores for items 2 to 4 were based on the average of ≥4 days of data in the most recent 7 days prior to randomization asdd, axillary sweating daily diary; asdd‑c, asdd‑children; bmi, body mass index; gt, topical glycopyrronium tosylate • the asdd item 2 responder rate (coprimary outcome; ≥4‑point improvement) was significantly greater for gt‑treated patients than for vehicle‑treated patients in atmos‑1 (53% vs 28%) and atmos‑2 (66% vs 27%) (p<0.001 both studies) • improvement in axillary sweating severity (asdd/asdd‑c item 2) was greater for gt‑ treated patients compared with vehicle‑treated patients at every study week (figure 2) – after 4 weeks of treatment in atmos‑1, scores improved 58% (‑4.3 point change) in gt‑treated patients and 35% (‑2.5) in vehicle‑treated patients compared with baseline – after 4 weeks of treatment in atmos‑2, scores improved 67% (‑4.9 point change) in gt‑treated patients and 36% (‑2.6) in vehicle‑treated patients compared with baseline figure 2. percent improvement from baseline in axillary sweating severity (asdd/asdd-c item 2) scores by week vehiclegt vehiclegt 80 60 40 20 0 p e r c e n t im p r o v e m e n t i n a x il la r y s w e a t in g s e v e r it y ( a s d d /a s d d -2 i t e m 2 ) s c o r e s atmos-1 week atmos-2 0 1 2 3 4 80 60 40 20 0 week 0 1 2 3 4 67% 36% 35% 58% data are representative of the intent‑to‑treat (itt) population; figures represent the change in scores in terms of percent improvement asdd item 2: during the past 24 hours, how would you rate your underarm sweating at its worst? 0 (no sweating at all) to 10 (worst possible sweating) asdd‑c item 2: thinking about last night and today, how bad was your underarm sweating? 0 (no sweating at all) to 10 (worst possible sweating) asdd, axillary sweating daily diary; asdd‑c, asdd‑children; gt, topical glycopyrronium tosylate • improvement in scores related to the impact of axillary sweating (asdd item 3) scores was greater for gt‑treated patients than vehicle‑treated patients at every study week (figure 3) – after 4 weeks of treatment in atmos‑1, scores improved by 63% (‑1.5 point change) in gt‑treated patients and 39% (‑0.8) in vehicle‑treated patients compared with baseline – after 4 weeks of treatment in atmos‑2, scores improved by 72% (‑1.7 point change) in gt‑treated patients and 41% (‑1.0) in vehicle‑treated patients compared with baseline figure 3. percent improvement from baseline in scores related to the impact of axillary sweating (asdd item 3) by week vehiclegt vehiclegt 80 60 40 20 0 p e r c e n t i m p r o v e m e n t in s c o r e s r e la t e d t o t h e i m p a c t o f a x il la r y s w e a t in g ( a s d d i t e m 3 ) atmos-1 week atmos-2 0 1 2 3 4 80 60 40 20 0 week 0 1 2 3 4 72% 41% 63% 39% data are representative of the intent‑to‑treat (itt) population of patients ≥16 years of age; figures represent the change in scores in terms of percent improvement asdd item 3: during the past 24 hours, to what extent did your underarm sweating impact your activities? 0 (not at all), 1 (a little bit), 2 (a moderate amount), 3 (a great deal), 4 (an extreme amount) asdd, axillary sweating daily diary; gt, topical glycopyrronium tosylate • improvement in scores related to the bother of axillary sweating (asdd item 4) was greater in gt‑treated patients than vehicle‑treated patients at every study week (figure 4) – after 4 weeks of treatment in atmos‑1, item 4 scores improved by 64% (‑1.7 point change) in gt‑treated patients and by 39% (‑0.9) in vehicle‑treated patients compared with baseline – after 4 weeks of treatment in atmos‑2, item 4 scores improved by 72% (‑1.9 point change) in gt‑treated patients and by 41% (‑1.0) in vehicle‑treated patients compared with baseline figure 4. percent improvement from baseline in scores related to the bother of axillary sweating (asdd item 4) by week vehiclegt vehiclegt 80 60 40 20 0 p e r c e n t im p r o v e m e n t in s c o r e s r e la t e d t o t h e b o t h e r o f a x il la r y s w e a t in g ( a s d d i t e m 4 ) atmos-1 week atmos-2 0 1 2 3 4 80 60 40 20 0 week 0 1 2 3 4 72% 41% 64% 39% data are representative of the intent‑to‑treat (itt) population of patients ≥16 years of age; figures represent the change in scores in terms of percent improvement asdd item 4: during the past 24 hours, how bothered were you by your underarm sweating? 0 (not at all bothered), 1 (a little bothered), 2 (moderately bothered), 3 (very bothered), 4 (extremely bothered) asdd, axillary sweating daily diary; gt, topical glycopyrronium tosylate • the proportion of patients who were negatively impacted by aspects of sweating (weekly impact items) decreased at week 4 for all patients regardless of treatment; the magnitude of the decrease was greater in patients treated with gt than with vehicle on all items, indicating greater improvement with gt treatment (figure 5) figure 5. proportion of patients answering ‘yes’ to weekly impact items 85.6% 32.1% a. needed to change shirt during the day 59.2% 23.7% b. needed ≥1 shower/bath a day 91.0% 38.8% c. felt less confident 98.5% 43.8% d. felt embarrassed 67.7% 17.9% e. avoided interactions 62.7% 13.8% f. kept from doing an activity 80.6% 50.5% a. needed to change shirt during the day 62.1% 43.1% b. needed ≥1 shower/bath a day 86.4% 58.7% c. felt less confident 93.2% 63.3% d. felt embarrassed 68.9% 34.9% e. avoided interactions 49.5% 21.1% f. kept from doing an activity 87.5% 22.5% a. needed to change shirt during the day 55.0% 14.9% b. needed ≥1 shower/bath a day 93.0% 33.3% c. felt less confident 96.0% 39.2% d. felt embarrassed 67.0% 15.8% e. avoided interactions 59.5% 10.8% f. kept from doing an activity 87.0% 55.0% a. needed to change shirt during the day 52.0% 24.8% b. needed ≥1 shower/bath a day 93.0% 61.5% c. felt less confident 97.0% 67.0% d. felt embarrassed 61.0% 34.9% e. avoided interactions 56.0% 31.2% f. kept from doing an activity baseline week 4 baseline week 4 80 100 60 40 20 0 80 100 60 40 20 0 80 100 60 40 20 0 80 100 60 40 20 0 p r o p o r t io n o f p a t ie n t s a n s w e r in g “ y e s ” t o w e e k ly i m p a c t i t e m s ( % ) gt vehicle p r o p o r t io n o f p a t ie n t s a n s w e r in g “ y e s ” t o w e e k ly i m p a c t it e m s ( % ) a t m o s -2 a t m o s -1 data are representative of the intent‑to‑treat (itt) population of patients ≥16 years of age gt, topical glycopyrronium tosylate • following treatment in atmos‑1 and atmos‑2, 73.6% and 80.4% of gt‑treated patients rated their axillary sweating as much or moderately better, compared with 38.2% and 40.6% of vehicle‑treated patients, respectively (figure 6) • following treatment in atmos‑1 and atmos‑2, more vehicle‑treated patients (29.4% and 36.5%, respectively) reported no difference or a little worsening in axillary sweating following treatment compared with those receiving gt (8.6% and 5.4%, respectively) figure 6. distribution of patient responses to pgic vehiclegt 52.3% 17.6% 1 much better 21.3% 20.6% 2 moderately better 17.8% 32.4% 3 a little better 8.1% 24.5% 4 no difference 0.5% 4.9% 5 a little worse 0%0% 6 moderately worse 0% 0% 7 much worse vehiclegt 63.7% 26.0% 1 much better 16.7% 14.6% 2 moderately better 14.2% 22.9% 3 a little better 4.9% 32.3% 4 no difference 0.5% 4.2% 5 a little worse 0%0% 6 moderately worse 0% 0% 7 much worse 80 60 40 20 0 p r o p o r t io n o f p a t ie n t r e s p o n s e s t o p g ic , % atmos-1 80 60 40 20 0 p r o p o r t io n o f p a t ie n t r e s p o n s e s t o p g ic , % atmos-2 data are representative of the intent‑to‑treat (itt) population of patients ≥16 years of age pcig item: overall, how would you rate your underarm sweating now as compared to before starting the study treatment? 1 (much better), 2 (moderately better), 3 (a little better), 4 (no difference), 5 (a little worse), 6 (moderately worse), 7 (much worse) gt, topical glycopyrronium tosylate; pcig, patient global impression of change conclusions • after 4 weeks, gt‑treated patients reported greater weekly average improvement than vehicle-treated patients on all asdd items (ie, severity, impact, and bother of axillary sweating on daily activities) that measured the daily burden of disease associated with axillary hyperhidrosis • at the end of treatment, fewer gt‑treated patients reported the occurrence of the specific negative behaviors or feelings associated with their excessive axillary sweating than did vehicle‑treated patients • following treatment, approximately 2‑fold more gt‑treated patients rated their axillary sweating as much or moderately better versus vehicle-treated patients • these additional results from atmos-1 and atmos-2 suggest that gt, if approved, has the potential to reduce the burden of disease for patients with axillary hyperhidrosis references 1. doolittle et al. arch dermatol res. 2016; 308 (10):743‑9. 2. bahar et al. j am acad dermatol. 2016; 75(6):1126‑33. 3. pariser et al. poster presented at: 25th european academy of dermatology and venereology congress; september 28‑october 2, 2016; vienna, austria. 4. pariser et al. poster presented at: 13th annual maui derm for dermatologists; march 20-24, 2017; maui, hi. acknowledgements the authors would like to thank sheri fehnel, dana dibenedetti, and lauren nelson, from rti health solutions, as well as diane ingolia and christine conroy, from dermira, inc., for their work developing the pro questionnaire. these studies were funded by dermira, inc. medical writing support was provided by prescott medical communications group. all costs associated with development of this poster were funded by dermira, inc. author disclosures dmp: consultant and investigator for dermira, inc. aah: consultant for dermira, inc.; employee of the university of texas medical school, houston, which received compensation from dermira, inc. for study participation. jd: employee of dermira, inc. jq: employee of qst consultations. dag: consultant and investigator for dermira, inc. fc17posterdermirapariserpatientreportesoutcomeshyperhidrosis.pdf skin july 2019 volume 3 issue 4 copyright 2019 the national society for cutaneous medicine 284 compelling comments dermatoethics in the “selfie” era jeanette r zambito, m.s. ed1, skylar n travis, md1 1university of rochester school of medicine and dentistry “please”, her mother implored. “the other kids make fun of her.” here with her thirteenyear-old daughter, mrs. h was requesting that we remove numerous milia from around her daughter’s eyes. her daughter was conspicuously quiet. perhaps she was shy. maybe she felt like she didn’t need to weigh in since her mother was taking care of it. or, maybe, it just wasn’t that important to her. as we discussed the benign nature of the patient’s milia, explaining that removal was not necessary or recommended, the mother’s eyes welled up and she whispered “i just don’t want her to be bullied anymore.” bullying is an issue that has received increasing attention in our culture, particularly with the rise of cyberbullying on social media sites such as facebook and snapchat. recent research demonstrates a link between cyberbullying and self-harm and suicidal behavior.1 nationwide, there are discussions in every sector, from education, to technology and law enforcement, on how to make kids feel more accepted. cyberbullying goes hand in hand with the rise of social media, the “selfie”, and increased pressure on children to present a perfect version of themselves at all times. this phenomenon will undoubtedly lead to pediatric dermatology patients requesting procedures that are purely cosmetic in nature at increasingly frequent rates. this poses many difficult questions for clinicians. what is considered a legitimate reason for a cosmetic procedure? who should the primary decision-maker be—the parent or the child? and where should we draw the line? acne, for example, can be considered largely a cosmetic issue. yet it is one that has a large enough impact on daily life and self-esteem that we regularly and routinely treat it. but how should we respond when faced with a child who is being bullied due to milia around the eyelids? what about the patient who insists that their lips aren’t plump enough? kylie jenner, younger sister of kim kardashian and co-star of the show keeping up with the kardashians, admitted during a 2015 episode that she had received lip augmentation with juvederm injections at the age of 17.2 (she had previously denied allegations that she had artificially enhanced her lips, claiming that it was the effect of lip liner). her full lips became a pop culture phenomenon, spawning the #kyliejenner challenge in which young girls attempted to recreate the star’s full-lips look with dermatologic consequences including edema, petechiae, ecchymoses, and scarring.3 as these issues spill over into the doctor’s office, we will need to ask ourselves: where do we draw the line with the proverbial lip liner? conflict of interest disclosures: none. skin july 2019 volume 3 issue 4 copyright 2019 the national society for cutaneous medicine 285 funding: none. corresponding author: skylar n travis, md dermatology resident, pgy4 university of rochester medical center skylar_travis@urmc.rochester.edu references: 1. john a, glendenning ac, marchant a, et al. self-harm, suicidal behaviours, and cyberbullying in children and young people: systematic review. j med internet res. 2018; 20(4):e129. 2. new york times. (2015). kylie jenner’s beauty routine: how she keeps it real. [online] available at: https://www.nytimes.com/2015/09/1 0/fashion/kylie-jenner-beautyregimen.html?_r=1. [accessed 28 nov. 2018]. 3. washington post. (2015). kylie jenner lip challenge: the dangers of ‘plumping that pout’. [online] available at: https://www.washingtonpost.com/ne ws/morningmix/wp/2015/04/21/kylie-jennerchallenge-the-dangers-of-plumpingthatpout/?noredirect=on&utm_term=.b0a6 4a85dc58 [accessed 28 nov. 2018]. skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 53 clinical management recommendations meeting the challenges of the dermatomyositis workup: a management paradigm amena alkeswani, bs1, lauren v graham, md, phd1 1department of dermatology, university of alabama at birmingham, birmingham, al dermatomyositis (dm) is a rare inflammatory myopathy with characteristic skin manifestations. this multisystem disorder is characterized by an increased frequency of pulmonary disease and malignancy. it has a female to male predominance of 2:1, with an average age at diagnosis of 40 years [1]. diagnosing dm can be challenging due to the heterogeneity of presentations and clinical features that may overlap with other disorders. although dm has had an established diagnostic criteria by bohan and peter since 1975, groups have re-examined the criteria to highlight the importance of skin findings [2-4]. this article will discuss the process of working-up dermatomyositis in an adult from a dermatologist’s point of view (appendix 1). patients often exhibit skin manifestations first, which emphasizes the importance of dermatologists in recognizing the specific skin findings. in fact, skin manifestations precede myositis in the vast majority of patients. most of these patients develop symptoms of myositis within 3-6 months, but it may take up to 2 years for these symptoms to appear [5]. in addition, about 10% of dm’s patients exhibit skin limited disease, known as amyopathic dermatomyositis [3]. gottron’s papules/sign are pathognomonic findings of dm [2]. they are defined as erythematous to violaceous papules or macules, maybe with scale, that occur symmetrically over the extensor surfaces of joints, such as the metacarpophalangeal joints, elbows, and knees. this finding is present in two third of dm patients and may mimic the appearance of some papulosquamous diseases, such as psoriasis [1]. heliotrope eruption is the most specific skin finding but is present in only half the patients [1]. it is defined as an erythematous to a violaceus patch on the upper eyelids that can present with periorbital edema. characteristic findings include facial erythema and photo distributed poikiloderma, including the v and shawl sign. these findings may mimic cutaneous lupus erythematosus (cle), especially earlier in the presentation when poikiloderma appears as erythema. nasolabial involvement in facial erythema can be helpful in distinguishing dm from cle’s malar rash. holster sign is poikiloderma that occurs on the photoprotected area of the lateral thighs. difficulty in detecting erythematous rashes in non-caucasian patients leads to delayed diagnosis and misrepresentation of disease what are the cutaneous manifestations? skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 54 severity [4]. palpation of the cutaneous findings can help detect the presence of blanchable erythema. periungual changes, such as erythema, telangiectasias, and cuticular hypertrophy, are common in dm but can resemble other connective tissue diseases such as scleroderma. dilated capillary loops can be seen on dermoscopy and may reflect disease activity [4]. pruritus often is a significant complaint for these patients and can be one of the first symptoms to develop [3]. scalp erythema and pruritus can be severe and should warrant evaluation for dm. nonscarring diffuse alopecia of the scalp may occur. mechanic hands, defined as hyperkeratosis of the lateral fingers and palms, flagellate erythema, and follicular hyperkeratosis are uncommon compatible findings of dm and is associated with antisythestase syndrome. flagellate erythema is rare and also can be seen in still’s disease, bleomycin-treatment, and shiitake mushroom dermatitis. panniculitis, lipodystrophy, vesiculobullous eruptions and calcinosis cutis are rarely seen in adult dm patient but are strongly associated with juvenile dm. patients may present with general complaints such as weakness or fatigue, resulting in an extensive differential. therefore, a thorough history is essential when it comes to diagnosing dm. the duration, mode of onset, and location need to be identified. questions regarding daily activities such as climbing stairs, hair grooming, or shaving can be utilized to localize the weakness. a history of recent infections, previous malignancies, travel, and family history can further aid in narrowing the differential. obtaining a medication list is crucial as some medication such as d-penicillamine, statins, sulfonamides, isoniazid, tamoxifen, chlorpromazine, antazoline, and phenylbutazone are known to cause a dmlike syndrome [4]. in addition, long-term hydroxyurea use may cause dm-like eruptions [4]. a complete review of systems can detect possible malignancy or one of the systemic features of dm such as dysphagia, arthralgia, or pulmonary involvement. a general physical exam should emphasize the skin, neurological and musculoskeletal systems. the musculoskeletal exam may identify the pattern of weakness and the extent of muscle involvement. typically, dm symmetrically affects the proximal muscle groups of the shoulder and pelvic girdle. however, in progressive disease all muscles may become involved. the neurological exam is central to help distinguish between myopathic and neuropathic etiologies, which may present with overlapping clinical features. autoantibodies are classified into two groups: myositis associated autoantibodies (maa) and myositis-specific autoantibodies (msa). they are useful in predicting the course of the disease as patients with a particular antibody tend to exhibit homogeneous clinical features [6]. therefore, it is recommended to obtain autoantibodies, which are available as sendout labs at most institutions. table 1 discusses the significance of the most common autoantibodies identified in dm patients. there have been strong suggestions to incorporate msa into the diagnostic criteria as their specificity exceeds 90% and they have a high cumulative sensitivity of 70-80% [6, 7]. what to look for when performing history and physical exam what is the utility of autoantibodies? skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 55 table 1: common myositis specific autoantibodies in dm and their clinical characteristics [6, 7]. idiopathic inflammatory myopathies (iim); juvenile dm(jd); interstitial lung disease (ild). melanoma differentiation-associated gene 5 (mda5); nuclear matrix protein-2 (nxp-2); small ubiquitin-like modifier activating (sae); signal recognition particle (srp); transcriptional intermediary factor-1γ (tif-1γ). autoantibody frequency clinical characteristic antisynthetases: anti jo-1,pl-7, pl-12, anti ej, anti oj, anti ks, anti zo, anti ha anti jo-1 is present in up to 40% of adults with iim -antisythestase syndrome (a constellation of interstitial lung disease, myositis, polyarthritis, raynaud’s phenomenon, fever, and mechanic’s hands) anti-srp 4-13% -necrotizing myopathy -high risk of cardiac involvement anti-tif-1γ up to 40% of patients with jd -jd -increased cancer risk in adults antinxp-2 up to 5% of adults up to 30% of jd patients -increased cancer risk in adults increased calcinosis in jd antisae up to 9% of adults increased cancer risk in adults anti-mda5 7-48% of adults amyopathic dm rapid ild elevation of any of the following muscle enzymes: creatine kinase, aldolase, aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase can be used to support the diagnosis of dermatomyositis [2]. patients may have at least one elevated muscle enzyme, though cases of amyopathic dm or significant loss of muscle mass are exceptions [8]. creatine kinase is very specific to skeletal muscle and is the most common serum marker used to diagnose and monitor the disease progression. although the levels can vary significantly, they are usually 10 folds higher than the normal level [9]. aldolase is the most sensitive enzyme and is elevated in more than 60% of patient in various stages of dm [10]. erythrocyte sedimentation rate (esr) elevation is not specific and is only present in 50% of dm patients [11]. it cannot be used for diagnosis but might be useful for monitoring the progression of muscle inflammation and response to treatment [11, 12]. furthermore, recent studies have suggested esr’s potential to screen for pulmonary involvement [12]. a complete blood count may detect a high white blood cell count and a low lymphocyte count, especially in males. also, low albumin and hematocrit can be found due to the inflammatory process [10]. antinuclear antibody is found in 2/3 of dm patients, but is not specific and have not shown to influence the prediction of the course of the disease [11]. electromyography (emg) is particularly useful to differentiate between neuropathic and myopathic etiologies and for selecting the highest yield site for possible muscle biopsy. abnormal findings consistent with dm include a short, small, polyphasic motor unit potentials; fibrillations, positive sharp waves, and insertional irritability; and bizarre, highfrequency repetitive discharges. these abnormal findings are detected in almost 90% of dm patients with muscle involvement what lab studies should be ordered? other diagnostic studies skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 56 [8]. emg may elevate muscle enzymes; therefore, muscle enzymes should be obtained prior to performing emg. magnetic resonance imaging (mri) can demonstrate the extent of muscle involvement and identify the best site for muscle biopsy if needed. however, the changes seen on mri are not specific to dm. skin biopsy is performed when evaluating for amyopathic dm or to help differentiate dm from other papulosquamous diseases. however, if the clinical findings are consistent, it is not necessary for diagnosis. skin biopsy is not reliable in distinguishing dm from cle. a skin biopsy of dm lesions classically demonstrates vacuolar interface dermatitis with mucin deposition in the dermis. muscle biopsy can be obtained but is not always necessary. infrequently, myositis may precede the cutaneous findings. a closed needle biopsy is preferred as it allows for a larger sample while preserving the orientation of muscle fibers. abnormal findings consistent with dm include perifascicular atrophy, predominant inflammatory infiltrate of cd4+ cells, and the overexpression of type i interferon-inducible genes. in patients newly diagnosed with dm, further studies are indicated based on the presences of clinical evidence of other organ involvement, such as cardiac, pulmonary, or esophageal disease. however, all patients must undergo screening for malignancy at the time of diagnosis. the evaluation includes a comprehensive history and physical examination. diagnostic studies to obtain include: complete blood count, liver function tests, kidney function tests, urinalysis, age and gender appropriate cancer screenings such as mammography, colonoscopy, and pap smear, fecal occult blood if colonoscopy is not indicated, pelvic and breast examination and pelvic ultrasound for women, and prostate examination for men. in addition, most experts recommend pulmonary function tests with diffusion capacity (pfts with dlco) and ct with iv contrast of the chest, abdomen, pelvis [13, 14]. providers should include the request to assess for interstitial lung disease in the ct orders. further work-up is indicated if any of the above tests yields an abnormal result. conflict of interest disclosures: none. funding: none. corresponding author: lauren v graham, md, phd university of alabama at birmingham birmingham, al lvgraham@uabmc.edu references: 1. kovacs, s.o. and s.c. kovacs, dermatomyositis. j am acad dermatol, 1998. 39(6): p. 899-920; quiz 921-2. 2. bohan, a. and j.b. peter, polymyositis and dermatomyositis (first of two parts). n engl j med, 1975. 292(7): p. 344-7. 3. sontheimer, r.d., dermatomyositis: an overview of recent progress with emphasis on dermatologic aspects. dermatol clin, 2002. 20(3): p. 387-408. 4. santmyire-rosenberger, b. and e.m. dugan, skin involvement in dermatomyositis. curr opin rheumatol, 2003. 15(6): p. 714-22. 5. strom, m.a., et al., association between atopic dermatitis and attention deficit indications for skin or muscle biopsy additional recommended screening tests mailto:lvgraham@uabmc.edu mailto:lvgraham@uabmc.edu skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 57 hyperactivity disorder in u.s. children and adults. br j dermatol, 2016. 175(5): p. 920-929. 6. sato s, murakami a, kuwajima a, takehara k, mimori t, kawakami a, et al. (2016) clinical utility of an enzymelinked immunosorbent assay for detecting anti-melanoma differentiation-associated gene 5 autoantibodies. plos one 11(4): e0154285. https://doi.org/10.1371/journal.pone. 0154285. 7. merlo, g., et al., specific autoantibodies in dermatomyositis: a helpful tool to classify different clinical subsets. arch dermatol res, 2017. 309(2): p. 87-95. 8. bohan, a., et al., computer-assisted analysis of 153 patients with polymyositis and dermatomyositis. medicine (baltimore), 1977. 56(4): p. 255-86. 9. dalakas, m.c., inflammatory muscle diseases. n engl j med, 2015. 372(18): p. 1734-47. 10. volochayev, r., et al., laboratory test abnormalities are common in polymyositis and dermatomyositis and differ among clinical and demographic groups. open rheumatol j, 2012. 6: p. 54-63. 11. koler ra, montemarano a. dermatomyositis. am fam physician. 2001 nov 1;64(9):1565-1573. 12. go, d.j., et al., elevated erythrocyte sedimentation rate is predictive of interstitial lung disease and mortality in dermatomyositis: a korean retrospective cohort study. j korean med sci, 2016. 31(3): p. 389-96. 13. leatham, h., et al., evidence supports blind screening for internal malignancy in dermatomyositis: data from 2 large us dermatology cohorts. medicine (baltimore), 2018. 97(2): p. e9639. 14. sparsa, a., et al., routine vs extensive malignancy search for adult dermatomyositis and polymyositis: a study of 40 patients. arch dermatol, 2002. 138(7): p. 885-90. https://doi.org/10.1371/journal.pone.0154285 https://doi.org/10.1371/journal.pone.0154285 https://doi.org/10.1371/journal.pone.0154285 https://doi.org/10.1371/journal.pone.0154285 skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 58 appendix 1: an overview of dm work-up. skin july 2019 volume 3 issue 4 copyright 2019 the national society for cutaneous medicine 279 brief articles expedited resolution of 5-fluorouracil-induced reaction and barrier dysfunction with white petrolatum melody maarouf mhs1, bryan w. kromenacker ma bsn1, eric e. brucks md2, vivian y. shi md3 1university of arizona, college of medicine, tucson, az 2university of arizona, department of medicine, tucson, az 3university of arizona, department of medicine, division of dermatology, tucson, az topical 5-fluorouracil (5-fu) is a commonly prescribed field treatment for diffuse actinic keratosis (ak).[1] 5-fu preferentially targets aks, inducing inflammation and skin barrier disruption, [2] with erythema, blistering, necrosis with erosion, and reepithelialization. complete ak clearance can be seen in up to 90% of patients who tolerate these side effects. [3] there is no standard recommendation on post-topical 5-fu wound care to minimize skin discomfort and inflammation. previously, erlendsson et al. attempted to mitigate the cutaneous reactions associated with topical ingenol-mebutate. following finalization of ak treatment, twice-daily application of topical clobetasol proprionate 0.05% for 4 days did not show significant reduction of local skin responses, pain, or pruritus. [4] maarouf et al., have shown that petrolatum is effective in improving post 5-fu erythema and skin hydration. [5] a 67-year-old caucasian male with diffuse facial ak (19 by count; left: 10 right: 9) actinic keratoses (ak) are precancerous lesions that develop on chronically sun-exposed skin. they frequently require prophylactic field treatment due to the risk of progression to squamous cell carcinoma. topical 5-fluorouracil (5-fu) is highly effective treatment for ak, yet leaves a patient with an exuberant erythematous reaction at treatment site, which can be embarrassing and uncomfortable. we report a case of a patient with diffuse facial ak who was treated with 5-fu twice daily for 2 weeks, resulting in fiery-red erythema and disrupted barrier function. application of pure ultra white petroleum jelly, an emollient preferred by dermatologists for post-operative wound healing, resulted in drastic decreased erythema and recovery time of post-treatment transepidermal water loss and hydration, compared to the contralateral, nonpetrolatum-treated side. additionally, petrolatum use did not disrupt the ak resolution endpoint. we suggest that petroleum jelly be used for the repair of 5-fu-induced barrier disruption and erythema to promote greater patient adherence. abstract introduction case report skin july 2019 volume 3 issue 4 copyright 2019 the national society for cutaneous medicine 280 underwent 5-fu treatment twice daily for 2 weeks. within 1 week, he experienced erythema, burning, and itching, which became robust and uncomfortable during the second week of treatment. after completing his 5-fu course, he applied vaseline pure ultra white petroleum jelly (covidien, mansfield, ma) to the right side of the face twice daily for 2 weeks, leaving the left side of the face untreated. four weeks following 5-fu initiation, 95% ak lesions had resolved and no lesion was present at 3 months follow-up. average clinician’s erythema assessment (0=clear skin with no signs of erythema to 4=severe erythema/fiery redness)[6] and skin barrier biophysical properties [hydration, transepidermal water loss (tewl)] were measured at baseline, weekly during 5-fu treatment, and for 2 more weeks during petrolatum intervention. facial erythema, hydration, and tewl progressively worsened during 5-fu treatment, peaking at 3-weeks. compared to the contralateral control side, petrolatum significantly reduced erythema, increased hydration, and decreased tewl (figure 1ad). hydration steadily declined throughout treatment, and sharply rose by week 5. in mixed-effects bivariate regressions across ointment conditions using face side as the grouping variable, erythema positively correlated with tewl (r =0.42, p=0.03) (figure 1e) and inversely correlated with hydration (r =-0.57, p=0.004) (figure 1f), suggesting that subjective erythema accurately reflected changes in skin barrier physiology. while an important therapy for prevention of scc, topical 5-fu is uncomfortable (figure 1a-c). the inflammatory response severity correlates closely with the degree of barrier dysfunction that persists weeks after the initiation and cessation of 5-fu use (figure 1d-e). thus, facial treatment is especially intolerable and cosmetically unacceptable. this report demonstrates that white petrolatum, a bland, cheap, and widely available barrier repair ointment, can significantly reduce erythema and repair barrier dysfunction. petrolatum is a semisolid mixture of hydrocarbons derived from heavy mineral oils, which resemble the components of intercellular epidermal lipids. in addition to forming a hydrophobic film on the skin surface, petrolatum’s hydrophobic nature allows it to diffuse into the epidermis. intercalation into intercellular spaces promotes modification of the lipid lattices to reinforce barrier integrity. [7] the therapeutic advantage of 5-fu is in disaccord with its high rates of symptomatology dissatisfaction. the prospect of lessening adverse effects and time to erythema resolution may increase patient tolerance and compliance for 5-fu treatment. additionally, the 100% resolution of ak count suggests that petrolatum does not reduce 5-fu efficacy. discussion skin july 2019 volume 3 issue 4 copyright 2019 the national society for cutaneous medicine 281 figure 1. (a) heatmap represents progressively increasing erythema during5-fu treatment (weeks 1-3), with decreasing erythema on the petrolatum-treated (r) side as early as week 4; heatmap represents progressively worsening skin barrier function, characterized by (b) increased tewl and (c) decreased hydration during 5-fu treatment (weeks 1-3), with faster recovery detected on the petrolatum-treated (r) side as early as week 4, compared to the non-petrolatum-treated (l) side; (d) scatterplot represents a positive correlation (r=0.42, p=0.03) between erythema and tewl; (e) scatterplot represents a negative correlation (r=-0.57, p = 0.004) between erythema and hydration. skin july 2019 volume 3 issue 4 copyright 2019 the national society for cutaneous medicine 282 white petrolatum is an effective therapeutic agent in reducing erythema and expediting skin barrier recovery following topical 5-fu. randomized controlled studies should aim to assess the erythemaand pain-reducing effects that alternative barrier repair modalities have on 5-fu-treated skin conflict of interest disclosures: none. funding: none. corresponding author: vivian y. shi, md assistant professor of medicine, dermatology division university of arizona vshi@email.arizona.edu references: 1. moy, r.l., clinical presentation of actinic keratoses and squamous cell carcinoma. j am acad dermatol, 2000. 42(1 pt 2): p. 8-10. 2. maarouf m, kromenacker b.w., brucks e.s., hendricks a.j., shi, v.y. 5-flouracilinduced erythema and transepidermal water loss associated with complete actinic keratosis resolution. j dermatolog ther, 2019. 32(3):e12890. epub ahead of print. 3. gupta, a.k., v. davey, and h. mcphail, evaluation of the effectiveness of imiquimod and 5-fluorouracil for the treatment of actinic keratosis: critical review and meta-analysis of efficacy studies. j cutan med surg, 2005. 9(5): p. 209-14. 4. erlendsson, a.m., karmisholt, k.e., haak, c.s., stender, i.m., haedersal m. topical corticosteroids has no influence on inflammation or efficacy after ingenol mebutate treatment of grade i to iii actinic keratosis (ak): a randomized clinical trial. jaad, 2016. 74(4): p/ 70915. 5. maarouf m, kromenacker b.w., brucks e.s., hendricks a.j., shi, v.y. reducing unpleasant side effects of topical 5floururacial treatment for actinic keratosis: a randomized controlled trial. j dermatolog treat. 2019. 1:1-5. epub ahead of print. 6. morales-burgos, a., m.p. loosemore, and l.h. goldberg, postoperative wound care after dermatologic procedures: a comparison of 2 commonly used petrolatum-based ointments. j drugs dermatol, 2013. 12(2): p. 163-4. 7. tan, j. and m. leoni, erythema of rosacea: validation of patient's selfassessment grading scale. j drugs dermatol, 2015. 14(8): p. 841-4 conclusion mailto:vshi@email.arizona.ed#u targeting ox40 with gbr 830, an ox40 antagonist, inhibits t cell-mediated pathological responses julie macoin1; r ami lissil a a1; pavankumar sancheti2; venk ateshwar reddy3; jonathan back1; gerhard wolff3 1glenmark pharmaceuticals sa , switzerl and; 2glenmark pharmaceuticals ltd., india; 3glenmark pharmaceuticals inc ., usa synopsis/objective ox40 (tnfrsf4, cd134) is a costimulatory receptor member of the tnfr superfamily expressed predominantly on activated t cells. binding of ox40 to its ligand ox40l (tnfsf4, cd252) leads to enhanced t  cell survival, proliferation, and effector functions. blocking the ox40/ox40l pathway is therefore a highly attractive target for a broad range of t cell-mediated autoimmune diseases. gbr  830, a humanized igg1 monoclonal antibody targeting ox40 with proven antagonistic properties and no detectable agonistic activity, blocks ox40l binding and ox40l-mediated t cell proliferation in vitro. the studies presented herein characterize the mechanism of action and immunomodulatory capabilities of gbr 830. methods and results ◾◾ gbr 830 suppresses t cell-mediated allogeneic responses with a potency similar to positive controls abatacept (cd28 blocker; figure 1) and efalizumab (lfa-1 blocker; data not shown) figure 1. human allogenic mixed lymphocyte reaction assay p ro lif e ra ti o n in h ib it io n ( % ) 75 100 50 25 0 -25 -50 igg ctrl abatacept gbr 830 one-way mixed lymphocyte reaction measured by 3h-thymidine incorporation. multiple allogeneic combinations were performed, and each data point represents the maximum t cell proliferation inhibition observed for a given combination. data are presented as mean ± sd. ctrl, control. ◾◾ gbr 830 blocks a strong t helper-mediated response in a human xenogeneic graft versus host disease (gvhd) model (figure 2) figure 2. xenogeneic human graft versus host disease model p e rc e n t s u rv iv a l 100 80 60 40 20 0 0 20 40 60 days r a ti o h c d 4 + / h c d 8 + i n b lo o d 2.0 1.5 1.0 0.5 0 day 14 vehicle etanercept (8mg/kg) gbr 830 1mg/kg gbr 830 10mg/kg treatments vehicle etanercept 8mg/kg gbr 830 1mg/kg gbr 830 10mg/kg a. survival b. human cd4+/cd8+ t cell ratio in peripheral blood scid mice were sublethally irradiated and reconstituted (intraperitoneal) with 30 million human pbmcs (8 mice/group with pbmcs from 2 different donors) on day 0. mouse nk cells were depleted by twice weekly injections of tmbeta1 antibody. gbr 830, etanercept, or vehicle were given weekly (intravenous) for six consecutive doses with first doses administered two days before pbmc injection. a) percent survival (including ethical sacrifice). b) ratio of human cd4+/cd8+ t cells in peripheral blood measured by flow cytometry at day 14. *p <0.05, log-rank test between indicated group and vehicle group. h, human; nk, natural killer; pbmc, peripheral blood mononuclear cell. ◾◾ gbr 830 significantly reduced memory antibody response to keyhole limpet hemocyanin (klh) in cynomolgus monkeys from day 84 onward, with no effect on primary antibody response to klh (figure 3) figure 3. t cell-dependent antibody response to klh in cynomolgus monkeys 1 15 22 25 29 klh 36 84 91 94 98 1 15 22 25 29 klh 36 84 91 # 94 98 g e o m e tr ic m e a n (n g /m l) 500,000 450,000 400,000 350,000 300,000 250,000 200,000 150,000 100,000 50,000 0 timepoint (day) g e o m e tr ic m e a n (n g /m l) 2,001,000 1,801,000 1,601,000 1,401,000 1,201,000 1,001,000 801,000 601,000 401,000 201,000 1,000 timepoint (day) igm igg group 1: placebo group 2: low dose group 3: medium dose group 4: high dose gbr 830 weekly gbr 830 weekly klh immunization timepoints are indicated in green. the primary anti-klh response was tested at days 15 and 29 with all dose groups: 5 animals/sex/ group for group 1 (placebo) and group 4 (gbr 830 high dose); 3 animals/sex/group for group 2 (gbr 830 low dose) and group 3 (gbr 830 medium dose). the memory response was tested at day 84 onward only with group 1 and group 4 recovery animals (2 animals/sex/group). the geometric mean values are calculated from the pooled data from males and females for each dose group. #p<0.05, *p<0.01 versus placebo. klh, keyhole limpet hemocyanin. ◾◾ out of 6 healthy donors, gbr 830 demonstrated equal efficacy (n=3;  representative donor 1) or greater efficacy (n=3; representative donor 2) versus abatacept in suppressing memory reactivation to tetanus toxoid (figure 4) figure 4. memory reactivation with tetanus toxoid x years later pbmcs readout proliferation healthy donor with historical tt vaccine + 20 20 4 0.8 20 4 0.8 20 20 0.164 0.8 20 4 0.160.8 (µg/ml) donor 1 in h ib it io n o f p ro lif e ra ti o n ( % ) 100 80 60 40 20 0 isotope control abatacept gbr 830 (µg/ml) donor 2 in h ib it io n o f p ro lif e ra ti o n ( % ) 100 80 60 40 20 0 isotope control abatacept gbr 830 a. tetanus toxoid vaccination model b. proliferation assay a) pbmcs were collected from healthy donors previously vaccinated with tt and incubated for 5 days with purified tt and isotype control, abatacept, or gbr 830. b)  proliferation was quantified by 3h-thymidine incorporation. percent inhibition of proliferation was determined relative to control with pbmc and tt only. pbmc, peripheral blood mononuclear cell; tt, tetanus toxoid. ◾◾ gbr 830 blocks memory reactivation to autoimmune antigens from various autoimmune diseases compared with no antibody or igg1 isotype control treatment (figure 5) figure 5. memory reactivation to autoimmune antigens s ti m u la ti o n in d e x 40 60 20 8 6 4 2 0 no ab gbr 830 no ab gbr 830 no ab gbr 830 ctrl gbr 830 sle ms ra uv proportion of antigen responders showing an e�ect of gbr 830 4/5 5/7 4/4 3/3 sle ms ra uv pbmcs were incubated with or without relevant antigens in presence or absence of gbr 830 or control antibodies. the response to antigen was measured by 3h-thymidine incorporation. the graph shows the stimulation index for all antigens in the control condition (no antibody or igg1 control) and gbr 830-treated condition. for ra, some samples responded to more than one antigen. the table shows the proportion of responders for which gbr 830 produced an inhibition of proliferation. each condition was performed in at least triplicates. the following antigens were selected for each disease: ms, myelin basic protein purified from human brain; ra, citrulinated peptides from aggrecan, vimentin, and fibrinogen proteins1; sle, smd183-119 peptide2; uv, human soluble antigen.3 if the stimulation index (ratio between the condition with the antigen and without antigen) was ≥2, the donor was considered a responder to that antigen. the effect of gbr 830 was assessed on all responders (sle, n=5; ms, n=7; ra, n=4; uv, n=3). ab, antibody; ctrl, control; ms, multiple sclerosis; pbmc, peripheral blood mononuclear cell; ra, rheumatoid arthritis; sle, systemic lupus erythematosus. uv,  uveitis. ◾◾ gbr 830 was equally effective as clobetasol propionate (temovate®) compared with isotype control in ameliorating the psoriasis phenotype in a human psoriatic skin transplant model (figure 6) ◾◾ a reduction in cd3+ t cell number was observed in the gbr 830 treatment group but was not statistically significant from the isotype control group figure 6. human psoriatic skin transplant in scid mice xenograft treatments 2-3 weeks a. human psoriatic skin transplant model b. epidermal thickness c. t cell infiltration donor 4 donor 1 is o ty p e c o n tr o l g b r 8 3 0 te m o va te donor 4 donor 1 is o ty p e c o n tr o l g b r 8 3 0 te m o va te e p id e rm a l t h ic k n e ss ( μ m ) 200 150 100 50 0 iso typ e c on tro l + n=11 gb r 8 30 hi gh do se + n=11 gb r 8 30 m ed . d os e + n=3 gb r 8 30 lo w d os e + n=3 te mo va te + n=5 xenograft treatments 2-3 weeks a. human psoriatic skin transplant model b. epidermal thickness c. t cell infiltration donor 4 donor 1 is o ty p e c o n tr o l g b r 8 3 0 te m o va te donor 4 donor 1 is o ty p e c o n tr o l g b r 8 3 0 te m o va te e p id e rm a l t h ic k n e ss ( μ m ) 200 150 100 50 0 iso typ e c on tro l + n=11 gb r 8 30 hi gh do se + n=11 gb r 8 30 m ed . d os e + n=3 gb r 8 30 lo w d os e + n=3 te mo va te + n=5 cd3+/total average standard deviation isotype control 0.237 0.31 gbr 830 0.142 0.15 temovate 0.136 0.162 a) full-thickness, 6-mm lesional skin punch biopsies (epidermis + dermis) from adult volunteers with psoriasis were grafted onto the dorsal area of scid mice. three to 5 days after graft transplantation, mice were treated with isotype control, gbr 830 (both intraperitoneal), or temovate® topical at 2x/week for 2 weeks. b) left panel: mean epidermal area and length of tissue were measured using aperio slide scanning software. mean epidermal thickness was calculated as area/length. *p< 0.05 (mannwhitney two-tailed or student two-tailed unpaired t-test). n indicates the number of donors and + indicates mean. right panel: representative images of transplanted tissue cross-sections stained with hematoxylin and eosin. c) left panel: immunohistochemistry of cd3+ t cells (dark brown) in transplanted tissue. right panel: t cell density based on cd3 immunohistochemistry. no statistical significance was observed due to inter-donor variability. donors 1 and 4 were treated with the high dose of gbr 830. histology of transplanted tissue was analyzed using a scan scope at 10x magnification. scid, severe combined immunodeficiency. conclusions ◾ these data suggest that gbr 830 has immunomodulatory capabilities in memory/chronic t helper cell-mediated pathological responses without pan immunosuppression (no impact on primary antibody responses) ◾ strong immune suppression focused on memory and chronic t cell responses but spared naïve t cell function ◾ blockade of ox40 by gbr 830 is expected to be a relevant therapeutic target in a broad range of autoimmune diseases re fe re nces 1. law sc, street s, yu c-ha, et al. arthritis research & therapy. 2012;14(3):r118. 2. riemekasten g, weiss c, schneider s, et al. annals of the rheumatic diseases. 2002;61(9):779-85. 3. de smet md, bitar g, mainigi s, nussenblatt rb. invest ophthalmol vis sci. 2001;42(13):3233-8. disclosures this study was funded by glenmark pharmaceuticals, sa. medical writing and editorial assistance was provided by prescott medical communications group, chicago, il. pr e s e nte d at th e fa ll c li n i c a l d e r m ato lo gy co n f e r e n c e o c to b e r 18-21, 2018 | l a s v e ga s , n v 20201211_bhatia_long term efficacy and safety long-term efficacy and safety of benzoyl peroxide cream, 5%, prepared with microencapsulation in papulopustular rosacea: results from an extension of two phase 3, vehicle-controlled trials n bhatia,¹ w werschler,² h baldwin,3 j sugarman,4 l stein gold,5 l green,6 e lain7 1. therapeutics research inc, san diego, ca; 2. spokane dermatology clinic and werschler aesthetics, spokane, wa; 3. acne treatment & research center, brooklyn, ny; 4. university of california san francisco, san francisco, ca; 5. henry ford health systems, detriot, mi; 6. aesthetic dermatology center, rockville, md; 7. saniva dermatology, pflugerville, tx conclusions the results from this long-term extension of two phase 3 randomized controlled trials demonstrated progressive clinical improvement as reflected by percentage of patients achieving iga success and reduction in erythema as well as good cutaneous safety and tolerability with e-bpo cream, 5% applied for up to 52 weeks in patients with rosacea. acknowledgments: the authors gratefully acknowledge the editorial and data analysis contributions of robert rhoades, phd and thomas prunty, cmpp of aramed strategies whose assistance was funded by sol-gel technologies, ltd. references: 1. erlich m, arie t, koifman n, talmon y. structure elucidation of silica-based core-shell microencapsulated drugs for topical applications by cryogenic scanning electron microscopy. j colloid interface sci. 2020;579:778-785. 2. bhatia n, werschler w, sugarman j, stein gold l. efficacy and safety of microencapsulated benzoyl peroxide cream, 5% in papulopustular rosacea: results from two phase 3, vehicle-controlled trials. 2020. in submission. to interact with and explore these data more intimately, please click here: https://www.solgelposters.com introduction • in a new microencapsulated formulation (e-bpo cream, 5%), the drug is entrapped in silica microcapsules. this extends drug delivery time to improve efficacy and potently reduces the potential for skin irritation.1 • the efficacy, safety, and tolerability of e-bpo cream, 5% were evaluated in two identical randomized, double-blind, phase 3 trials which demonstrated significant superiority of this encapsulated bpo over vehicle for percentage of patients achieving success (clear or almost clear) on the investigators global assessment (iga) and reducing the number of lesions.2 • e-bpo cream, 5% was also well tolerated with adverse events (aes) and cutaneous safety and tolerability was comparable to that for vehicle. methods assessments safety and tolerability • any adverse events (aes) including local and systemic events. • investigators’ cutaneous safety assessment rating (dryness and scaling) and patients’ local tolerability assessments rating (itching and burning/stinging) on scales ranging from 0 (none) to 3 (severe). • physical examinations and recording of vital signs. additional assessments • at each extension visit (baseline and weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40/end of study), patients were assessed using a 5-point iga scale of rosacea severity. • relapse was defined as the number of treatment-free days until the first retreatment and was calculated for each patient. retreatment was initiated at the time of relapse. • erythema and telangiectasia (each score on a scale of 0-3). • rosacea quality of life questionnaire. 2 • this report summarizes results from the 40-week extension of the two phase 3 trials e-bpo cream, 5%. the primary objective was evaluation of safety. a kaplan-meier analysis of time to first retreatment is shown in figure 2. 66.5% 67.6% 67.2%70% 60% 50% 40% 30% 20% 10% 0% vehicle in phase 3 trial (n=172) e-bpo cream, 5% in phase 3 trial (n=363) all patients (n=535) p er ce nt o f p at ie nt s a ch ie vi ng ig a su cc es s a t w ee k 40 all patients (n=535) vehicle e-bpo cream, 5% phase 3 trials (n=172) in phase 3 trials (n=363) age (years) ethnicity hispanic or latino not hispanic or latino not reported/unknown race american indian or alaska native asian black or african american native hawaiian or other pacific islander w hite multiple/other mean (sd) median iga 3 moderate 4 severe 155 (29.0%) 380 (71.0%) 492 (92.0%) 28.4 (13.11) mean (sd) 52.0 (12.75) 51.3 (13.88) 51.5 (13.52) median sex 53.0 (22-81) 52.0 (19-81) 53.0 (19-81) male 52 (30.2%) 101 (27.8%) 153 (28.6%) female 120 (69.8%) 262 (72.2%) 382 (71.4%) 53 (30.8%) 102 (28.1%) 119 (69.2%) 261 (71.9%) 0 0 0 1 (0.6%) 0 1 (0.2%) 9 (5.2%) 27 (7.4%) 36 (6.7%) 0 1 (0.3%) 1 (0.2%) 1 (0.6%) 1 (0.3%) 2 (0.4%) 161 (93.6%) 331 (91.2%) 0 3 (0.8%) 3 (0.6%) 27.6 (12.83) 28.8 (13.24) 23.0 (15-70) 24.0 (15-70) 24.0 (15-70) 477 (89.2%)157 (91.3% 320 (88.2%) 15 (8.7%) 43 (11.8%) 58 (10.8%) 100 % 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 0 4 8 12 16 36 40 44 48 52 p e rc e n t o f p a ti e n ts w it h d ry ne ss s e v e ri ty o f… 20 24 28 32 w eeks from first dose of epsolay mi l d or none none moderate or severe 100 % 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 0 4 8 12 16 36 40 44 48 52 p e rc e nt o f p at ie nt s w it h s ca lin g s ev er ity o f… 20 24 28 32 w eeks from first dose of epsolay mi l d or none none moderate or severe 100 % 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 0 4 8 12 16 36 40 44 48 52 p e rc e nt o f p at ie nt s w it h it ch in g s ev er ity o f… 20 24 28 32 w eeks from first dose of epsolay mi l d or none none moderate or severe 100 % 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 0 4 8 12 16 36 40 44 48 52 p e rc e nt o f p at ie nt s w it h b u rn in g /s ti n g in g s ev er ity o f… 20 24 28 32 w eeks from first dose of epsolay mi l d or none none moderate or severe e-bpo cream, 5% (n=535) any teae any serious teae death discontinued e-bpo cream, 5% due to a teae discontinued from the study due to a teae maximum severity of teae severe moderate mild relationship to study drug related not related teaes reported for > 2 % of patients nasopharyngitis upper respiratory tract infection results patients • a total of 547 patients were enrolled, including 363 previously treated with e-bpo cream, 5% and 184 previously treated with vehicle. the percentage of patients who completed the study was 85.7% according to an ad-hoc analysis, which included those discontinued early due to the sponsor’s decision to terminate the study as completers. patient characteristics are summarized in table 1. iga success • iga success was defined as achievement of clear or almost clear at the week 40 visit. • at this evaluation, 67.2% of patients achieved success. this was the case for 67.6% of the patients who received e-bpo cream, 5% in the double-blind studies and 66.5% of those who received vehicle (figure 1). retreatment • a mean of 1.4 retreatments was reported for all patients in the extension. the median number of treatment-free days was 58 (95% ci = 57.0-64.0). • for patients with a score of 0 at the beginning of the extension (n=48), the mean time to first retreatment was 125.1 days (sd = 99.3, median = 112.5 days) and the mean number of retreatments was 1.15. the respective values for patients with a score of 1 (n=122) were 92.6 days (sd = 75.2, median = 61.5 days) and 1.66 (sd = 1.16) (p<0.05 for both comparisons) (figure 3). erythema and telangiectasia • facial erythema generally improved during the course of the study. there was an increase from baseline to week 40 in the percentage of patients with no or mild erythema (10.1% to 76.2%). the proportion of patients with mild or no telangiectasia at baseline was 58.2% and this increased to 80.1% by week 40. rosacea quality of life questionnaire • the results of the rosaqol questionnaire showed mean decreases (improvements) from baseline to week 40/end of treatment for the total score (0.7), symptom subscale score (0.7), functional subscale score (0.4), and emotional subscale score (0.8). safety and tolerability • for each of the cutaneous safety and tolerability parameters, there were small increases in the percentages of patients with no or mild signs/symptoms over 52 weeks (figure 4). • 185 patients (34.6%) reported at least one treatment-related ae (teae) (table 2). most teaes were mild or moderate in severity and were not considered to be related to studytreatment. • no deaths were reported in the study. • 10 patients (1.9%) experienced serious aes, none of which were considered to be related to studytreatment. patients • patients met the following criteria when entering the phase 3 trials: ▪ males and females ≥18 years of age with moderate-to-severe rosacea with a baseline iga score of 3 (moderate severity) or 4 (severe) on a severity scale of 0-4. ▪ ≥15 and ≤70 total inflammatory lesions and ≤2 nodules (defined as a papule or pustule >5 mm in diameter). study design and treatment • all patients were assigned to treatment with e-bpo cream, 5%: ▪ if a patient was assessed as clear (iga = 0) or almost clear (iga = 1), he or she was instructed not to apply e-bpo cream, 5% and it was not dispensed. ▪ if a patient was assessed as mild, moderate, or severe (iga = 2-4), e-bpo cream, 5% was dispensed, and the patient was instructed to apply the product daily. • patients were followed for up to 40 additional weeks in the extension and for up to a total of 52 weeks, including the time in the phase 3 trial. 2x trials / phase 3 / 52 weeks table 1. baseline demographic and clinical characteristics figure 4. percentages of patients reporting mild/no and no: a. dryness. b. scaling. c. itching. d. burning/stinging at each evaluation (open symbols denote results limited to patients who received e-bpo cream, 5% during the phase 3 trials) figure 1. percentage of patients achieving of iga success at 40 weeks figure 2. time to first retreatment table 2. adverse events 0% 10% 40% 30% 20% 50% 80% 70% 60% 90% 100% p er ce nt o f p at ie nt s w ith ou tr el ap se 0 10 20 30 40 50 60 70 80 90 100 110 120 130 140 150 160 170 180 190 200 210 220 230 240 250 260 270 280 290 treatment free days until first retreatment censored 58.0 125.1 92.6 0 20 40 60 80 100 120 all patients(n=535) e-b po in rct, iga = 0 e-b po in rct, iga = 1 at week 12 (n=48) at week 12 (n=122) m e a n t im e t o f ir st r e tr e a tm e n t( d a ys ) 1.4 1.15 1.66 0 0.5 1 1.5 140 2 all patients (n=535) e-b po in rct, iga = 0 e-b po in rct, iga = 1 at week 12 (n=48) at week 12 (n=122) m e a n n u m b er o f re tr e at m en ts p=0.001 figure 3. time to retreatment and number of retreatments for all patients and for patients treated with e-bpo cream, 5% during the phase 3 trials and who had an iga score of 0 (clear) or 1 (almost clear) at the end of 12-week double-blind treatment p=0.02 185 (34.6%) 10 (1.9%) 0 5 (0.9%) 4 (0.7%) 8 (1.5%) 81 (15.1%) 96 (17.9%) 17 (3.2%) 168 (31.4%) 29 (5.4%) 12 (2.2%) long-term efficacy and safety of benzoyl peroxide cream, 5%, prepared with microencapsulation in papulopustular rosacea: results from an extension of two phase 3, vehicle-controlled trials skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 286 covid concept covid-19 associated onychomadesis jesse y. liu, md1, jesse j. veenstra, md1 1department of dermatology, henry ford hospital, detroit, mi to date, various cutaneous manifestations of coronavirus disease 2019 (covid-19) have been reported,1 including but not limited to morbilliform, urticarial, pernio-like, livedo-reticularis-like, hair loss, and myriad other presentations. reported covid-19 nail changes have included beau’s lines2 as well as one report of onychomadesis.3 here, we report an additional case of onychomadesis suspected to be related to covid-19. a 59-year-old african american male patient without history of dermatologic problems developed self-reported fever of up to 104of at home, chills, diarrhea, and cough. he was evaluated in the emergency room, where his vitals included fever of 100.6of, respiratory rate of 24/min, and o2 saturation of 100%. he received nasopharyngeal swab demonstrating real-time reverse transcription polymerase chain reaction (rtpcr) positive for covid-19, but no additional bloodwork. he was discharged home and improved without additional treatments while he quarantined. throughout his course, he denied any rash or skin changes. three months after his covid-19 diagnosis, noted rapid darkening of multiple fingernails. three weeks later, he noted sudden partial separation of multiple fingernails from their respective nailbeds, and subsequently presented to dermatology clinic. the initially affected nails included the left second fingernail and right third, fourth, and fifth fingernails. these nail plates remained attached to the distal nailbed or lateral nailfold, with complete detachment on the opposite nailfold or the proximal nailfold. toenails were not affected. these findings were associated with moderate pain. during the initial visit, nail plate was examined histologically and demonstrated parakeratosis with bacterial colonization. periodic acid-schiff (pas) stain was negative for fungi. at patient’s return visit three months later, the patient experienced interval loss of nail plates on all fingernails. he has had partial nail regrowth, with a thin brittle nail plate covering approximately half the nailbed. the patient was recommended to pursue a watchful waiting approach. to add to the patient’s medical history, the patient had a history of hiv, well-controlled on lamivudine-zidovudine and nevirapine for several years, with recent undetectable viral load and cd4-count over 1200. he had a remote history of treated tuberculosis and treated syphilis. he denied any preceding medication changes, illnesses, trauma, or other nail exposures prior to his symptoms. he did not recall any preceding skin lesions that would be suggestive of hand-foot-andmouth disease (hfmd). skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 287 figure 1. fingernails upon initial presentation. figure 2. fingernails on 3-month followup. we present a case of onychomadesis in an hiv patient with recent covid-19 infection and no other obvious etiologies of onychomadesis. onychomadesis has historically been associated with a variety of causes, including drugs, trauma, inflammatory states such as stevensjohnson syndrome or kawasaki disease, and infections such as hfmd. speculated mechanisms4 for hfmd-related skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 288 onychomadesis may include matrix arrest due to fever, direct viral replication within the matrix, or inflammation proximal to the nail matrix which results in distal embolisms. these mechanisms may all be possible with covid-19, which features a microangiopathic pathophysiology. 5 this case report highlights the many manifestations of covid-19 infection, and the need for a high index of suspicion for covid-19 related cutaneous complications. conflict of interest disclosures: none funding: none corresponding author: jesse y. liu, md department of dermatology henry ford hospital detroit, mi email: jesse.y.liu.md@gmail.com references: 1. young s, fernandez ap. skin manifestations of covid-19. cleve clin j med. 2020 may 14. doi: 10.3949/ccjm.87a.ccc031. epub ahead of print. pmid: 32409442. 2. alobaida s, lam jm. beau lines associated with covid-19. cmaj. 2020;192(36):e1040. 3. senturk n, ozdemir h. onychomadesis following covid-19 infection: is there a relationship? dermatol ther. 2020;e14309. 4. salgado f, handler mz, schwartz ra. shedding light on onychomadesis. cutis. 2017 jan;99(1):33-36. pmid: 28207011. 5. ackermann m, verleden se, kuehnel m, et al. pulmonary vascular endothelialitis, thrombosis, and angiogenesis in covid-19. n engl j med. 2020 jul 9;383(2):120-128. doi: 10.1056/nejmoa2015432. epub 2020 may 21. pmid: 32437596; pmcid: pmc7412750. skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 82 skinmages recognizing adnexal tumors in skin of color jessica kay sterner, ba1, benjamin rushing, ba2, gage rensch, md3 1 university of missouri school of medicine 2 university of mississippi medical center school of medicine 3 tulane university department of dermatology the eccrine poroma is a benign adnexal tumor composed of epithelial cells originating from the terminal duct of the sweat gland. the tumor is rare, with an incidence of 0.001 to 0.008%.1 radiation exposure has been suggested to trigger the development of poromas as case reports have documented multiple poromas in areas of chronic radiation dermatitis. poromas are not known to have any ethnic, racial, familial or sex predilection.2 patients of any age may be affected, but incidence increases in adulthood. poromas typically present as an asymptomatic, slow-growing papule, nodule, or plaque. their color can vary from skincolored, red, brown, or bluish, and typically occur on the palms and soles.3 our patient was a 64-year-old mexican male presenting to dermatology clinic for a lesion skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 83 on his left abdomen. he reported that the lesion had been slowly enlarging for two years and was asymptomatic. the patient had no personal or family history of skin cancer. physical examination revealed a pink to grey, polypoid tumor on the left abdomen (figure 1). the differential diagnosis included acrochordon, condyloma, verrucous carcinoma, basal cell carcinoma, and melanoma. histopathology showed a polypoid tumor with a markedly acanthotic epidermis with broad interconnecting rete containing small uniform rounded squamous cells. there were foci of vacuoles compatible with poral differentiation and some gland-like lumina. the tumor was diagnosed as an eccrine poroma. there were some pigmented cells and a melan-a immunostain highlighted some dendritic melanocytes in focal areas within the tumor. this case highlights the importance of recognizing pigmented adnexal tumors in skin of color and represents a rare location for an eccrine poroma. conflict of interest disclosures: none funding: none acknowledgements: andrea murina, md corresponding author: jessica sterner, bs 1 hospital dr. columbia, mo 65212 phone: 6362190780 email: jksdm3@health.missouri.edu references: 1. cárdenas ml, díaz cj, rueda r. pigmented eccrine poroma in abdominal region, a rare presentation. colomb med (cali). 2013;44(2):115-117. published 2013 jun 30. 2. ahmed jan n, masood s. poroma. [updated 2021 jul 20]. in: statpearls [internet]. treasure island (fl): statpearls publishing; 2021 jan-. 3. wankhade v, singh r, sadhwani v, kodate p. eccrine poroma. indian dermatol online j. 2015 jul-aug;6(4):304-5. doi: 10.4103/22295178.160296. pmid: 26225348; pmcid: pmc4513423. mailto:jksdm3@health.missouri.edu powerpoint presentation objective efficacy and safety of tralokinumab plus topical corticosteroids in patients with severe atopic dermatitis and prior history of dupilumab treatment: a post hoc subgroup analysis from ecztra 7 trial jan gutermuth1, andrew pink2, margitta worm3, lise soldbro4, thomas mark4, joshua corriveau5, christian bjerregård øland4, stephan weidinger6 • ad is a chronic inflammatory disease,1 characterized by eczematous skin lesions and multiple symptoms, including pruritus, sleep disturbance, and depression2-4 • tralokinumab is a high-affinity, fully human, monoclonal antibody designed to specifically neutralize interleukin-13, a key driver of the underlying inflammation in ad5-7 • the phase 3 ecztra 7 trial (nct03761537) met its primary endpoint of easi-75 at week 16, confirming tralokinumab plus topical corticosteroids (tcs) is superior to placebo plus tcs in treating severe atopic dermatitis (ad) in patients not adequately controlled by, or with contraindications to, oral cyclosporine a • there can be inadequate disease control with currently available treatment options and many patients with severe ad continue to experience high disease burden to describe the efficacy and safety of tralokinumab in a subgroup of ecztra 7 patients with prior history of dupilumab treatment 1department of dermatology, universitair ziekenhuis brussel and vrije universiteit brussel, brussels, belgium; 2st john’s institute of dermatology, guy’s and st thomas’ nhs foundation trust, london, uk; 3division of allergy and immunology, department of dermatology, venereology and allergy, charité – universitätsmedizin berlin, berlin, germany; 4leo pharma a/s, ballerup, denmark; 5leo pharma inc., madison, nj, usa; 6department of dermatology and allergy, university hospital schleswig-holstein, campus kiel, kiel, germany introduction methods • ecztra 7 was a randomized, double-blinded, multicenter, placebo-controlled phase 3 trial (figure 1) • key inclusion criteria for ecztra 7: o adult patients with ad for ≥1 year with inadequate response to topical or documented systemic medication in the past year o disease not adequately controlled with, or patients with contraindications to, use of oral cyclosporine a o ad involvement of ≥10% body surface area o easi ≥20 and iga ≥3 at screening and at baseline o worst daily pruritus numeric rating scale (nrs) average score of ≥4 during the week prior to baseline table 1. baseline demographics and clinical characteristics for randomized subjects in ecztra 7. patient characteristics references disclosures conclusions this post hoc subgroup analysis indicates that dupilumab-experienced patients can benefit from tralokinumab + tcs as needed. • overall frequencies of adverse events in dupilumab-experienced patients treated with tralokinumab + tcs as needed were consistent with the pooled analysis of tralokinumab phase 2 and 3 trials8 • due to the small sample size, further data involving more patients are needed to confirm these findings 1. weidinger s, novak n. lancet. 2016;387:1109–22; 2. eckert l, et al. j am acad dermatol. 2017;77:274–9.e273; 3. silverberg ji, et al. ann allergy asthma immunol. 2018;121:340–7; 4. dalgard fj, et al. j invest dermatol. 2015;135:984–91; 5. bieber t. allergy. 2020;75:54–62; 6. tsoi lc, et al. j invest dermatol. 2019;139:1480–9; 7. popovic b, et al. j mol biol. 2017;429:208–19; 8. simpson et al. safety of specifically targeting interleukin 13 with tralokinumab in adult patients with moderate-to-severe atopic dermatitis: pooled analysis of five randomised, doubleblind, placebo-controlled phase 3 and phase 2 trials. poster presented at: 29th eadv congress; 29-31 october 2020; virtual. jan gutermuth reports honoraria as a consultant/advisory board member/ speaker and/or received grants from abbvie, genzyme, leo pharma, lilly, pfizer, regeneron, and sanofi. andrew e. pink has acted as an advisor/speaker for abbvie, almirall, janssen, la roche-posay, leo pharma, lilly, novartis, pfizer, sanofi, and ucb. margitta worm has served as a scientific advisor and/or clinical trial investigator and/or paid speaker for abbvie, alk, allergopharma, aimmune, boehringer ingelheim, dermira, eli lilly, galderma, janssen, leo pharma, mylan, novartis, pfizer, regeneron and sanofi-genzyme. lise soldbro, thomas mark, joshua corriveau, and christian bjerregård øland are employees of leo pharma a/s. stephan weidinger is co-principal investigator of the german atopic eczema registry treatgermany. he has received institutional research grants from sanofi deutschland gmbh, leo pharma, and la roche-posay, has performed consultancies for sanofi-genzyme, regeneron, leo pharma, abbvie, pfizer, eli lilly, kymab and novartis, he has also lectured at educational events sponsored by sanofi-genzyme, regeneron, leo pharma, abbvie, novartis and galderma, and is involved in performing clinical trials with many pharmaceutical industries that manufacture drugs used for the treatment of psoriasis and atopic eczema. acknowledgements • the ecztra 7 clinical trial was sponsored by leo pharma • editorial support was provided by clair geary, phd of alphabet health (new york, ny), supported by leo pharma, according to good publication practice guidelines (https://www.ismpp.org/gpp3). results dupilumab-naive dupilumab-experienced all (n=263) all (n=14) tralokinumab + tcs (n=6) placebo + tcs (n=8) variable n median iqr n median iqr n median iqr n median iqr ad duration, years 262 26.0 18.0, 34.0 14 34.0 15.0, 44.0 6 17 15.0, 43.0 8 34.0 21.0, 47.5 age, years 263 33.0 25.0, 45.0 14 51.5 43.0, 57.0 6 50.0 43.0, 56.0 8 51.5 42.0, 62.5 bsa (%) 263 52.0 35.0, 70.0 14 56.5 34.0, 70.0 6 58.5 50.0, 72.0 8 54.5 33.5, 65.0 dlqi 257 16.0 11.0, 21.0 14 15.0 8.0, 18.0 6 11.0 7.0, 16.0 8 16.5 10.5, 21.5 easi 261 28.7 22.4, 39.5 14 35.5 24.8, 39.6 6 37.3 29.0, 39.6 8 32.3 23.5, 38.9 scorad 261 68.9 61.5, 78.9 14 73.6 61.2, 77.0 6 72.6 58.0, 73.8 8 76.7 64.7, 82.2 worst daily pruritus nrs (weekly average) 259 7.4 6.6, 8.3 14 6.7 5.4, 8.0 6 5.9 5.3, 7.6 8 7.4 6.2, 8.9 iga 4, n (%) 263 129 (49.0) 14 8 (57.1) 6 5 (83.3) 8 3 (37.5) • among dupilumab-experienced patients at week 16, 100% (n/n, 6/6) of patients receiving tralokinumab + tcs achieved easi-75 without the use of rescue therapy, compared to 50% (4/8) of those receiving placebo + tcs (difference [95% ci]: 50.0 [15.4, 84.6]; table 2) • numerically higher proportions of dupilumab-experienced patients receiving tralokinumab + tcs achieved iga 0/1 (4/6, 66.7%; placebo + tcs: 3/8, 37.5%; difference: 29.2 [-21.3, 79.6]) and improvement in worst daily pruritus nrs (weekly average) ≥4 points (3/6, 50%; placebo + tcs: 3/8, 37.5%; difference: 12.5 [39.7, 64.7]) at week 16 • similarly, at week 26, numerically higher proportions of dupilumab-experienced patients receiving tralokinumab + tcs achieved easi-75 (6/6, 100%; placebo + tcs: 3/8, 37.5%; difference: 62.5 [29.0, 96.0]), iga 0/1 (4/6, 66.7%; placebo + tcs: 2/8, 25%; difference: 41.7 [-6.5, 89.9]), and improvement in worst daily pruritus nrs (weekly average) ≥4 points (3/6, 50%; placebo + tcs: 3/8, 37.5%; difference: 12.5 [-39.7, 64.7]), compared to placebo + tcs table 3. adverse events in dupilumab-experienced subjects through 26 weeks • no serious adverse events occurred in either treatment group • from a safety perspective, there were 2 patients who had previously discontinued dupilumab due to conjunctivitis; adverse events of conjunctivitis were not reported for either patient during 26 weeks of tralokinumab + tcs treatment table 2. binary efficacy endpoints in dupilumab-experienced subjects. figure 1. ecztra 7 trial design. • dupilumab-experienced (n=14) and dupilumab-naïve (n=263) cohorts had comparable baseline characteristics, except that median (interquartile range, iqr) age was 51.5 (43.0, 57.0) years for dupilumab-experienced patients and 33.0 (25.0, 45.0) years for dupilumab-naïve patients (table 1) • median (iqr) easi and percentage of patients with an iga of 4 were 35.5 (24.8, 39.6) and 57.1% among dupilumab-experienced patients and 28.7 (22.4, 39.5) and 49.0% among dupilumab-naïve patients, respectively • among dupilumab-experienced patients, baseline and clinical characteristics were similar between the tralokinumab + tcs as needed (n=6) and placebo + tcs as needed (n=8) groups (table 1) o 50% of patients in each of these two groups discontinued dupilumab due to either lack of efficacy or safety concerns visit endpoint tralokinumab + tcs (n=6) placebo + tcs (n=8) difference (95% ci)† week 16 easi75 6 /6 (100.0%) 4 /8 (50.0%) 50.0 (15.4,84.6) iga 0/1 4 /6 (66.7%) 3 /8 (37.5%) 29.2 (-21.3,79.6) itch nrs≥4* 3 /6 (50.0%) 3 /8 (37.5%) 12.5 (-39.7,64.7) week 26 easi75 6 /6 (100.0%) 3 /8 (37.5%) 62.5 (29.0,96.0) iga 0/1 4 /6 (66.7%) 2 /8 (25.0%) 41.7 (-6.5,89.9) itch nrs≥4* 3 /6 (50.0%) 3 /8 (37.5%) 12.5 (-39.7,64.7) †estimated treatment difference and 95% ci from mantel-haenszel analysis with treatment as only strata *improvement in worst daily pruritus nrs (weekly average) ≥4 points from baseline tralokinumab + tcs (n=6) placebo + tcs (n=8) any adverse event 4 /6 (66.7%) 7 /8 (87.5%) any serious adverse event 0 /6 (0.0%) 0 /8 (0.0%) conjunctivitis* 1 /6 (16.7%) 1/8 (12.5%) *search was done for adverse event of special interest: conjunctivitis • eligible patients were randomized 1:1 to subcutaneous tralokinumab 300 mg every 2 weeks with tcs as needed or placebo with tcs as needed for a treatment period of 26 weeks, following a 600 mg loading dose on day 0 • for this analysis, prior history of dupilumab treatment was confirmed and further details were collected via queries before trial unblinding • dupilumab-experienced patients are defined as those with a confirmed history of dupilumab use prior to the trial • cochran-mantel-haenszel with treatment as only strata was used for analysis ad, atopic dermatitis; easi, eczema area and severity index; iga, investigator’s global assessment; q2w, every 2 weeks; tcs, topical corticosteroid. tralokinumab 300 mg + tcs placebo + tcs treatmentscreening safety follow-up ecztra 7 (n=140) ecztra 7 (n=137) 1:1 randomization up to 6 weeks washout of ad medication except tcs/tci 300 mg q2w after initial loading dose (600 mg) 16 weeks0–6 40 weeks8 26 weeksweeks from treatment start visit number –2 1 2 3 11 16 177 primary endpoint tralokinumab response in dupilumab-experienced patients safety • through the 26 weeks, 66.7% (4/6) of dupilumab-experienced patients receiving tralokinumab + tcs reported any adverse event, compared to 87.5% (7/8) of those receiving placebo + tcs (table 3) • one placebo patient reported 2 events of conjunctivitis, 1 mild and 1 of moderate severity; 1 tralokinumab patient reported 1 mild event of conjunctivitis efficacy and safety of tralokinumab plus topical corticosteroids in patients with severe atopic dermatitis and prior history of dupilumab treatment: a post hoc subgroup analysis from ecztra 7 trial restricted mean survival time and cure-rate modeling in estimating relapse-free survival benefit with adjuvant dabrafenib + trametinib treatment in melanoma john m. kirkwood,1 reinhard dummer,2 axel hauschild,3 mario santinami,4 victoria atkinson,5 vanna chiarion sileni,6 james larkin,7 marta nyakas,8 andrew haydon,9 caroline dutriaux,10 jacob schachter,11 caroline robert,12 laurent mortier,13 hiya banerjee,14 tomas haas,15 monique tan,16 mike lau,17 dirk schadendorf,18 georgina v. long,19 mario mandalà20 1melanoma program, upmc hillman cancer center, university of pittsburgh, pittsburgh, pa, usa; 2department of dermatology, university hospital zürich skin cancer center, zürich, switzerland; 3department of dermatology, university hospital schleswig-holstein, kiel, germany; 4melanoma and sarcoma unit, department of surgery, fondazione irccs istituto nazionale dei tumori, milano, italy; 5division of cancer services, princess alexandra hospital, gallipoli medical research foundation, university of queensland, greenslopes, qld, australia; 6melanoma cancer unit, department of experimental and clinical oncology, veneto oncology institute-irccs, padova, italy; 7department of medical oncology, royal marsden nhs foundation trust, london, uk; 8department of cancer, oslo university hospital, the norwegian radium hospital, oslo, norway; 9melanoma service, department of medical oncology, the alfred hospital, melbourne, vic, australia; 10service de dermatologie, centre hospitalier universitaire de bordeaux, hôpital saint-andré, bordeaux, france; 11division of oncology, ella lemelbaum institute for immuno-oncology and melanoma, sheba medical center, tel hashomer, and sackler school of medicine, tel aviv university, tel aviv, israel; 12dermatology service and melanoma research unit, gustave roussy and paris-sud-paris-saclay university, villejuif, france; 13service de dermatologie, université de lille, inserm u 1189, lille, france; 14clinical development and analytics, novartis pharmaceuticals corporation, east hanover, nj, usa; 15clinical development and analytics, novartis pharma ag, basel, switzerland; 16oncology clinical development, novartis pharmaceuticals corporation, east hanover, nj, usa; 17global medical affairs, novartis pharma ag, basel, switzerland; 18department of dermatology, comprehensive cancer center (westdeutsches tumorzentrum), university hospital essen, essen, and german cancer consortium, heidelberg, germany; 19department of medical oncology, melanoma institute australia, the university of sydney, and royal north shore and mater hospitals, sydney, nsw, australia; 20department of oncology and hematology, papa giovanni xxiii cancer center hospital, bergamo, italy background • in combi-ad analysis, 5-year relapse-free survival (rfs) rates were 52% in patients with stage iii braf v600– mutant melanoma who received ≤ 12 months of dabrafenib + trametinib compared with 36% in those who received placebo1 • kaplan-meier and cox regression analyses have been used to assess adjuvant treatment effects based on time-to-event analyses1-3 • unfortunately, these statistical methods do not account for nonproportional hazards and the fact that some patients never experience relapse4-8 • to overcome these limitations, we evaluated treatment effects in combi-ad using: – restricted mean survival time (rmst): population average for the length of event-free survival time estimated by the area under a survival curve up to a specified time point that accounts for nonproportional hazards4-7 – cure-rate modeling: a statistical approach to model timeto-event data that estimates the proportion of patients in each arm who may never experience an event of interest (eg, relapse)8,9 methods • combi-ad (nct01682083) is a double-blind, randomized, phase iii trial that compared 12 months of adjuvant dabrafenib 150 mg twice daily + trametinib 2 mg once daily vs 2 matched placebos in patients with resected stage iii braf v600e/k–mutant melanoma (figure 1) – patients were stratified by braf v600e or v600k status and disease stage (by ajcc 7 criteria) • rmst analysis – the length of event-free survival time (ie, rfs) was estimated by assessing the area under the kaplan-meier curve up to 60 months of follow-up time in each treatment arm • cure-rate modeling – the use of a cure-rate model is considered appropriate because it is reasonable to assume there is a subset of patients in each disease substage who are “cured” by resection alone and will remain relapse free. this assumption is supported by the appearance of a plateau in rfs kaplan-meier curves – a mixed weibull cure-rate model was used to estimate the proportion of patients who might never experience disease relapse figure 1. combi-ad study design key eligibility criteria • completely resected cutaneous melanoma • braf v600e/k mutant • stage iiia, iiib, or iiic (ajcc 7) • resection ≤ 12 weeks before randomization • no prior systemic anticancer therapy • ecog ps 0-1 n = 870 stratified by: • braf mutation (v600e or v600k) • disease stage (iiia, iiib, or iiic) r 1:1 n = 438 dabrafenib 150 mg bid + trametinib 2 mg qd n = 432 2 matched placebos treatment (12 months)a primary endpoint: rfs secondary endpoints: os, dmfs, ffr, safety follow-upb until the end of study ajcc, american joint committee on cancer; ajcc 7, ajcc cancer staging manual, 7th edition; bid, twice daily; dmfs, distant metastasis–free survival; ecog ps, eastern cooperative oncology group performance status; ffr, freedom from relapse; os, overall survival; qd, once daily; r, randomization; rfs, relapse-free survival. a or until disease recurrence, death, unacceptable toxicity, or withdrawal of consent. b patients were followed up for disease recurrence until the first recurrence and thereafter for survival. results rmst • median duration of follow-up was 60 months in the dabrafenib + trametinib arm and 58 months in the placebo arm (data cutoff, november 8, 2019) • rmst across the stage iii patient population was improved in the dabrafenib + trametinib arm (41.5 months [95% ci, 39.4-43.6 months]) vs the placebo arm (28.7 months [95% ci, 26.3-31.2 months]) (figure 2; table 1) – these results suggest that on average, over a 60-month period, patients treated with dabrafenib + trametinib gain an additional 12.8 months of remaining relapse free vs placebo figure 2. overall rmst at 60 months 0 3 6 9 12 15 18 21 24 27 30 33 36 39 months since randomization s ur vi va l p ro ba bi lit y 12.8-month rmst difference 42 45 48 51 54 57 60 63 66 69 72 75 78 81 438 411 391 376 354 329 298 278 262 254 242 236 229 226 217 211 204 201 195 164 133 100 80 41 17 7 2 0 432 dab + tram no. at risk pbo dab + tram pbo 335 280 250 219 200 185 176 168 166 158 155 147 144 140 139 136 133 132 116 99 74 56 29 13 1 0 0 0.0 0.2 0.1 0.3 0.5 0.4 0.6 0.7 0.9 1.0 0.8 dab, dabrafenib; pbo, placebo; rmst, restricted mean survival time; tram, trametinib. rmst: subgroup analysis • rmst was improved with dabrafenib + trametinib across all ajcc 7 stage iii substages, with the greatest difference in rmst between arms reported in patients with stage iiib and iiic disease (table 1; figure 3a-c) table 1. rmst at 60 months overall stage iiiaa stage iiiba stage iiica dab + tram (n = 438) pbo (n = 432) dab + tram (n = 83) pbo (n = 71) dab + tram (n = 169) pbo (n = 187) dab + tram (n = 181) pbo (n = 166) events, n 187 259 25 26 69 117 90 112 rmst (95% ci), mo 41.5 (39.4-43.6) 28.7 (26.3-31.2) 50.4 (46.7-54.2) 42.2 (36.4-47.9) 41.2 (37.7-44.7) 29.0 (25.4-32.6) 38.0 (34.6-41.3) 22.8 (18.9-26.8) rmst difference (95% ci), mo 12.8 (9.5-16.0) 8.2 (1.4-15.1) 12.2 (7.2-17.2) 15.1 (10.0-20.3) dab, dabrafenib; pbo, placebo; rmst, restricted mean survival time; tram, trametinib. a per american joint committee on cancer’s ajcc cancer staging manual, 7th edition. figure 3. rmst at 60 months in the (a) stage iiia, (b) stage iiib, and (c) stage iiic subgroups (ajcc 7) 83 81 80 79 76 74 70 66 62 62 61 60 58 55 53 52 51 51 50 42 36 28 25 11 2 0 71 59 56 53 50 45 44 42 41 41 39 38 35 35 34 34 33 31 31 25 22 14 13 5 2 0 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 66 69 72 75 months since randomization 8.2-month rmst difference dab + tram (n = 83) pbo (n = 71) 169 161 151 144 134 124 110 103 99 95 91 89 86 86 84 81 80 78 75 61 52 37 26 16 9 5 2 0 187 161 135 120 102 94 84 79 74 73 68 67 65 63 60 60 58 57 56 51 42 33 25 16 6 1 0 0 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 66 69 72 75 78 81 months since randomization 12.2-month rmst difference dab + tram (n = 169) pbo (n = 187) 181 165 156 149 141 128 115 107 99 95 88 85 83 83 78 76 71 70 68 60 44 34 28 13 5 2 0 166 109 84 72 64 58 54 52 50 49 48 47 44 43 43 42 42 42 42 37 32 25 17 7 4 0 0 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 66 69 72 75 78 months since randomization 15.1-month rmst difference dab + tram (n = 181) pbo (n = 166) dab + tram (n = 83) pbo (n = 71) 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 a. stage iiia s ur vi va l p ro ba bi lit y no. at risk dab + tram (n = 169) pbo (n = 187) 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 s ur vi va l p ro ba bi lit y no. at risk b. stage iiib dab + tram (n = 181) pbo (n = 166) 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 c. stage iiic s ur vi va l p ro ba bi lit y no. at risk ajcc, american joint committee on cancer; ajcc 7, ajcc cancer staging manual, 7th edition; dab, dabrafenib; pbo, placebo; rmst, restricted mean survival time; tram, trametinib. cure-rate analysis • the estimated cure rate in the overall stage iii population was 51% (95% ci, 46%-56%) in the dabrafenib + trametinib arm compared with 35% (95% ci, 30%-40%) in the placebo arm (figure 4) figure 4. cure-rate model analysis months since randomization s ur vi va l p ro ba bi lit y 0 6 12 18 24 30 36 42 48 54 60 66 72 78 84 0.0 0.2 0.4 0.6 0.8 1.0 dab + tram km estimated cure rate (95% ci) 51 (46-56)dab + tram (n = 438) 35 (30-40)pbo (n = 432) pbo km dab + tram cure-rate model pbo cure-rate model 16% absolute difference dab, dabrafenib; km, kaplan-meier; pbo, placebo; tram, trametinib. cure-rate analysis: subgroup analysis • the estimated cure rate was improved with dabrafenib + trametinib across all ajcc 7 stage iii substages, with the greatest difference between arms reported in patients with stage iiib and iiic disease (figure 5a-c) figure 5. cure-rate model analysis for the (a) stage iiia, (b) stage iiib, and (c) stage iiic subgroups (ajcc 7) s ur vi va l p ro ba bi lit y 0.0 0.2 0.4 0.6 0.8 1.0 months since randomization 0 6 12 18 24 30 36 42 48 54 60 66 72 78 84 84 84 estimated cure rate (95% ci) estimated cure rate (95% ci) a. stage iiia 63 (49-77)dab + tram (n = 83) 52 (33-71)pbo (n = 71) 11% absolute difference dab + tram km pbo km dab + tram cure-rate model pbo cure-rate model s ur vi va l p ro ba bi lit y 0.0 0.2 0.4 0.6 0.8 1.0 months since randomization 0 6 12 18 24 30 36 42 48 54 60 66 72 78 dab + tram km pbo km dab + tram cure-rate model pbo cure-rate model b. stage iiib 54 (46-62)dab + tram (n = 169) 33 (26-40)pbo (n = 187) 21% absolute difference s ur vi va l p ro ba bi lit y 0.0 0.2 0.4 0.6 0.8 1.0 months since randomization 0 6 12 18 24 30 36 42 48 54 60 66 72 78 estimated cure rate (95% ci) c. stage iiic 43 (35-51)dab + tram (n = 181) 28 (21-36)pbo (n = 166) 15% absolute difference dab + tram km pbo km dab + tram cure-rate model pbo cure-rate model ajcc, american joint committee on cancer; ajcc 7, ajcc cancer staging manual, 7th edition; dab, dabrafenib; km, kaplan-meier; pbo, placebo; tram, trametinib. conclusions • rmst and cure-rate model analyses complement and enhance conventional statistical approaches, including kaplan-meier and cox regression analyses, and may facilitate clinical interpretation of treatment effects for oncologists and patients • results from rmst and cure-rate modeling analyses suggest that treatment with dabrafenib + trametinib leads to durable rfs benefit compared with placebo – rmst analysis suggests that over a 60-month period, patients treated with dabrafenib + trametinib gain 12.8 months of rfs on average compared with placebo – there was an absolute increase of 16% in the proportion of patients who were cured in the dabrafenib + trametinib arm vs the placebo arm • these analyses provide insights into long-term clinical benefits of adjuvant therapy with dabrafenib + trametinib; overall survival analysis is currently ongoing references 1. hauschild a, et al. asco 2020 [abstract 10001]. 2. weber js, et al. esmo 2019 [abstract 1310o]. 3. eggermont am, et al. asco 2020 [abstract 10000]. 4. a'hern rp. j clin oncol. 2016;34(28):3474-3476. 5. kim dh, et al. jama cardiol. 2017;2(11):1179-1180. 6. pak k, et al. jama oncol. 2017;3(12):1692-1696. 7. uno h, et al. j clin oncol. 2014;32(22):2380-2385. 8. othus m, et al. clin cancer res. 2012;18(14):3731-3736. 9. huang l, et al. cancer. 2008;112(10):2289-2300. acknowledgements we thank the patients and their families for participating in this study. we also thank all investigators and site staff for their contributions. we thank lali sandalic (novartis pharmaceuticals corporation) for providing statistical analysis support. we also thank maurizio voi, md (novartis pharmaceuticals corporation), for guidance and critical review. we thank zareen khan, phd, from articulatescience llc, for medical editorial assistance with this presentation, which was funded by novartis pharmaceuticals corporation (east hanover, nj), in accordance with good publication practice (gpp3) (https://www.ismpp.org/gpp3) guidelines and international committee of medical journal editors recommendations. this study was sponsored by glaxosmithkline; dabrafenib and trametinib are assets of novartis as of march 2, 2015. combi-ad is registered at clinicaltrials.gov (nct01682083) and conducted in accordance with study protocol brf115532. first author disclosures jm kirkwood reports grants and personal fees from amgen, bristol myers squibb, checkmate pharmaceuticals, and novartis, and grants from castle biosciences, immunocore llc, and iovance, outside of the presented work. presented online as part of the winter clinical dermatology virtual conference 2021; january 16-24, 2021. previously presented online as part of the esmo virtual congress 2020; september 19-21, 2020. 3 ways to instantly download an electronic copy of this poster to your mobile device or email a copy to your computer or tablet text: q143b7 to: 8nova (86682) us only +18324604729 north, central and south americas; caribbean; china +447860024038 uk, europe & russia +46737494608 sweden, europe visit the web at: https://novartis.medicalcongressposters.com/default.aspx?doc=143b7 scan this qr code copies of this e-poster obtained through qr, ar and/or text key codes are for personal use only and may not be reproduced without written permission of the authors. standard data or message rates may apply. http://novartis.medicalcongressposters.com/default.aspx?doc=ae593 background & objectives ■ psoriasis (pso) is an inflammatory skin disease associated with a variety of psychiatric comorbidities such as anxiety and depression. ■ psychiatric comorbidities are associated with higher healthcare resource utilization and costs in pso patients.1 ■ this study aimed to evaluate trends in the prevalence of psychiatric comorbid conditions for patients with moderate-to-severe pso in a commercially-insured us population. methods study design and data sources ■ this was a retrospective, cross-sectional study among a commercially insured population in the us. ■ de-identified us administrative claims were extracted from the truven health marketscan commercial claims database in the calendar years of 2014, 2015 or 2016, respectively. figure 1. patient selection members ≥18 years of age with continuous enrollment (n=19,343,284) patients with ≥1 medical claim with a diagnosis of pso (n=148,774) patients with ≥1 pso diagnosis plus ≥1 systemic or biologic pso medication (n=22,999) 2014 members ≥18 years of age with continuous enrollment (n=14,749,130) patients with ≥1 medical claim with a diagnosis of pso (n=119,136) patients with ≥1 pso diagnosis plus ≥1 systemic or biologic pso medication (n=27,300) 2015 members ≥18 years of age with continuous enrollment (n=14,716,660) patients with ≥1 medical claim with a diagnosis of pso (n=122,143) patients with ≥1 pso diagnosis plus ≥1 systemic or biologic pso medication (n=30,380) 2016 study cohorts ■ moderate to severe pso cohort: patients with ≥1 pso diagnosis and ≥1 prescribed systemic or biologic pso medication were selected in each calendar year (2014, 2015 or 2016). ■ non-pso (control) cohort: members with no diagnosis of pso, or disorders similar to pso, were randomly selected from 2014-2016 and matched to pso patients in a 1:1 ratio on age, gender, health plan type and region. study measures ■ the number of patients with the following psychiatric comorbidities were described in each calendar year — anxiety and/or depression: ≥1 diagnosis of anxiety or depression — treated anxiety and/or depression: ≥1 diagnosis of anxiety or depression plus a prescription for anxiolytics, antipsychotics, or antidepressants filled within ±30 days of diagnosis • treated major depressive disorder (mdd) a subset of treated anxiety and/or depression: ≥1 mdd diagnosis — untreated anxiety and/or depression: ≥1 diagnosis of anxiety or depression but without a prescription for any of the above pharmacotherapies filled during each calendar year — other psychiatric conditions: bipolar disorder, dementia, schizophrenic disorder, substance abuse disorder, and suicidal ideation statistical analysis ■ differences between the two study cohorts, across the 3 years respectively, were assessed for statistical significance using the t-test for continuous variables, and chi-square or fisher's exact test for categorical variables. ■ all statistical analyses were conducted using sas enterprise guide 7 (sas institute inc.; cary, nc). results demographic characteristics ■ a total of 29,999 patients with moderate to severe pso in 2014, 27,300 patients in 2015, and 30,380 patients in 2016 were selected. ■ demographic characteristics were similar between patients with moderate-to-severe pso and their matched controls, and were similar across cohorts from each of the 3 years included. ■ the mean age of patients was 48 years for all cohorts; slightly more than half of the patients were males, the majority resided in the south or west regions, and most patients were primarily covered by a ppo health plan (table 1). table 1. demographic characteristics of the study patients 2014 2015 2016 matched moderate to severe pso matched non-pso matched moderate to severe pso matched non-pso matched moderate to severe pso matched non-pso n patients 29,999 29,999 27,300 27,300 30,380 30,380 age (mean, sd) 47.8 11.2 47.8 11.2 48.0 11.2 48.0 11.2 47.9 11.4 47.9 11.4 18-44 (n, %) 10,620 35.4% 10,620 35.4% 9,379 34.4% 9,379 34.4% 10,474 34.5% 10,474 34.5% 45-64 19,337 64.5% 19,337 64.5% 17,887 65.5% 17,887 65.5% 19,862 65.4% 19,862 65.4% 65+ 42 0.1% 42 0.1% 34 0.1% 34 0.1% 44 0.1% 44 0.1% gender (n, %) male 15,853 52.8% 15,853 52.8% 14,153 51.8% 14,153 51.8% 15,697 51.7% 15,697 51.7% female 14,146 47.2% 14,146 47.2% 13,147 48.2% 13,147 48.2% 14,683 48.3% 14,683 48.3% region (n, %) northeast 6,100 20.3% 6,100 20.3% 4,939 18.1% 4,939 18.1% 5,082 16.7% 5,082 16.7% north central 5,884 19.6% 5,884 19.6% 5,340 19.6% 5,340 19.6% 5,903 19.4% 5,903 19.4% south 12,850 42.8% 12,850 42.8% 13,248 48.5% 13,248 48.5% 15,229 50.1% 15,229 50.1% west 4,264 14.2% 4,264 14.2% 3,708 13.6% 3,708 13.6% 4,062 13.4% 4,062 13.4% unknown 901 3.0% 901 3.0% 65 0.2% 65 0.2% 104 0.3% 104 0.3% commercial plan type (n, %) hmo 2,872 9.6% 2,872 9.6% 2,506 9.2% 2,506 9.2% 2,745 9.0% 2,745 9.0% ppo 18,179 60.6% 18,179 60.6% 16,787 61.5% 16,787 61.5% 18,219 60.0% 18,219 60.0% pos 1,725 5.8% 1,725 5.8% 1,923 7.0% 1,923 7.0% 2,026 6.7% 2,026 6.7% cdhp/hdhp 4,408 14.7% 4,517 15.1% 4,593 16.8% 4,649 17.0% 5,621 18.5% 5,756 18.9% others* 1,089 3.6% 980 3.3% 1,139 4.2% 1,083 4.0% 1,375 4.5% 1,240 4.1% unknown 1,726 5.8% 1,726 5.8% 352 1.3% 352 1.3% 394 1.3% 394 1.3% *includes comprehensive/indemnity, epo, missing or unknown. clinical characteristics [figure 2] ■ compared with matched controls, patients with moderate-to-severe pso across each of the 3 years studied had a significantly higher overall burden of comorbidity, as measured by the quan-charlson comorbidity index (all p<0.001). ■ the moderate-to-severe pso cohort had a significantly higher percentage of patients with hypertension, hyperlipidemia, diabetes, obesity, and thyroid disease (all p<0.001). ■ compared with matched controls, the moderate-to-severe pso cohort also had a significantly higher percentage of patients with concomitant medication use, including opioids, antihypertensives and anticholinergics (all p<0.001), across the 3-year study period. figure 2. top five most frequently occurring comorbid conditions and concomitant medications among study patients 35% 36% 37% 35% 35% 34% 15% 16% 16% 13% 16% 20% 13% 13% 14% 26% 27% 27% 27% 27% 27% 9% 10% 10% 7% 10% 12% 10% 11% 10% 0.0% 10.0% 20.0% 30.0% 40.0% 50.0% 2014 2015 2016 2014 2015 2016 2014 2015 2016 2014 2015 2016 2014 2015 2016 2014 2015 2016 2014 2015 2016 2014 2015 2016 2014 2015 2016 2014 2015 2016 matched moderate to severe pso matched non-pso matched moderate to severe pso matched non-pso hypertension hyperlipidemia diabetes obesity thyroid disease 35.30% 36.3% 37.0% 34.6% 34.9% 34.2% 15.4% 15.7% 15.7% 12.9% 16.0% 19.5% 13.0% 13.5% 13.7% 25.70% 27.0% 27.2% 26.7% 27.3% 26.6% 9.2% 9.8% 10.1% 7.4% 9.7% 11.9% 9.6% 10.5% 10.3% 0.0% 5.0% 10.0% 15.0% 20.0% 25.0% 30.0% 35.0% 40.0% 45.0% 50.0% opioids respiratory medication antihypertensives anticholinergics antihyperlipidemics prevalence of anxiety and/or depression [figure 3] ■ the prevalence of patients with an anxiety and/or a depression diagnosis among moderate to severe pso patients increased from 18.3% in 2014 to 19.7% in 2016, as compared with 12.2% (p<0.001) in 2014 and 13.1% (p<0.001) in 2016 for matched controls. ■ similarly, the prevalence of treated anxiety and/or depression among moderate to severe pso patients increased from 14.5% in 2014 to 15.9% in 2016, as compared with 9.0% (p<0.001) in 2014 and 9.7% (p<0.001) in 2016 for matched controls. — the prevalence of treated mdd among moderate to severe pso patients increased from 3.4% in 2014 to 8.6% in 2016, as compared with 2.0% (p<0.001) in 2014 and 2.9% (p<0.001) in 2016 for matched controls. ■ the percentage of patients with untreated anxiety and/or depression was about 2-3% for both cohorts across the 3-year study period. figure 3. prevalence of anxiety and/or depression among study patients 0.0% 5.0% 10.0% 15.0% 20.0% 25.0% 30.0% 2014 2015 2016 treated anxiety/depression matched moderate to severe pso matched non-pso 0.0% 2.0% 4.0% 6.0% 8.0% 10.0% 2014 2015 2016 untreated anxiety/depression matched moderate to severe pso matched non-pso 0.0% 5.0% 10.0% 15.0% 20.0% 25.0% 30.0% 2014 2015 2016 anxiety/depression diagnosis matched moderate to severe pso matched non-pso 0.0% 2.0% 4.0% 6.0% 8.0% 10.0% 2014 2015 2016 treated mdd matched moderate to severe pso matched non-pso prevalence of other psychiatric conditions [table 2] ■ across the 3-year study period, a significantly higher percentage of patients with moderate-to-severe pso had bipolar or substance abuse disorders compared with controls (all p<0.001). ■ no substantial difference in the prevalence of dementia, schizophrenic disorders, and suicidal ideation was observed between the two cohorts over the 3-year study period. table 2. prevalence of other psychiatric conditions among study patients 2014 2015 2016 matched moderate to severe pso matched non-pso p-value matched moderate to severe pso matched non-pso p-value matched moderate to severe pso matched non-pso p-value n=29,999 n=29,999 n=27,300 n=27,300 n=30,380 n=30,380 bipolar disorders 1.4% 0.7% <.001 1.4% 0.8% <.001 1.3% 0.8% <.001 dementia 0.1% 0.1% 0.527 0.1% 0.1% 0.647 0.1% 0.1% 1.000 schizophrenic/delusional disorders 0.1% 0.1% 0.808 0.1% 0.1% 0.805 0.1% 0.1% 0.622 substance abuse disorder 7.5% 4.8% <.001 7.9% 5.0% <.001 7.3% 4.5% <.001 suicidal ideation 0.2% 0.1% 0.058 0.2% 0.1% 0.035 0.3% 0.2% 0.011 limitations ■ administrative claims data were collected for facilitating payment for healthcare services; therefore, definitive diagnoses are not available and the true prevalence of treated anxiety and/or depression may be underestimated. ■ the study was composed of patients covered by commercial insurance; therefore, the results may not be generalizable to pso patients with other or no insurance coverage. conclusions ■ the prevalence of anxiety and/or depression was significantly higher among patients with moderateto-severe pso compared with matched controls without pso over the period spanning 2014-2016. ■ the prevalence of mdd among patients with moderate-to-severe pso more than doubled over the years 2014-2016. ■ compared with matched controls, the moderate-to-severe pso cohort had a significantly higher percentage of patients with concomitant medication use, including opioids, antihypertensives and anticholinergics. ■ these findings suggest that pso, as a systemic disease, is associated with higher rates of comorbid psychiatric disorders, such as anxiety and depression than for patients without pso. ■ while further research is needed, pso treatments that improve psychiatric symptoms, such as anxiety and depression, may provide additional incremental benefit to patients and the healthcare system. reference 1. feldman sr, tian h, gilloteau i, et al. bmc health serv res. 2017; 17: 337. this study was supported by janssen scientific affairs, llc. trends in prevalence of psychiatric comorbidities among patients with moderate to severe psoriasis q. cai, ms, msph1; a. teeple, pharmd1; b. wu, ms1; s. shrivastava, beng2; e. muser, pharmd, mph1 1janssen scientific affairs, titusville, nj; 2mu-sigma, bengaluru, india skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 60 brief article successful treatment of confluent and reticulated papillomatosis with minocycline topical 4% foam hanna lateef, bs1, ali kraish, ba2; farooq lateef, md, faad3 1 florida state university college of medicine 2 ross university college of medicine 3 orlando dermatology inc. confluent and reticulated papillomatosis was first recognized in 1927 by henri gougerot and alexandre carteaud as papillomatose pigmentée innominée, and subsequently papillomatose pigmentée confluente et reticulée.1,2 in 1937, the first reported case in the united states was reported by fred wise and wilbert sachs, who renamed the condition confluent and reticulated papillomatosis (crp).3,4 crp is an uncommon dermatosis with many proposed etiologies, including a disorder of keratinization, a reaction to malassezia, an outbreak in relation to an endocrinopathy, a response to bacterial infection, a response to uv light, a genetic factor, and a process involving amyloidosis.5 under both light and electron microscopy, crp is found to affect the epidermis through disordered and hyperproliferative keratinization.6 crp typically presents as papules or plaques, approximately 3-5 mm in diameter, which merge centrally in a confluent pattern and scatter peripherally in a reticular pattern.7 populations in which lesions occur most commonly are young adults, although it has been reported to affect all races and ages worldwide, with an unidentifiable preference for gender.5,8 typically, lesions initially occur near the inframammary folds and epigastric skin. they can extend to the center of the chest, and both the upper and lower back and abdomen.9 the following is diagnostic criteria for crp proposed by davis et al, which has been consistent across existing literature on crp case series: (i) clinical findings include brown, scaly patches and macules, at least parts of which display reticulation and papillomatosis; (ii) the rash involves the upper trunk and neck; (iii) negative fungal staining of scales; (iv) no response to abstract this report discusses the use of a novel treatment method for confluent and reticulated papillomatosis (crp) in a middle-aged african american woman. the patient was hesitant to begin oral antibiotics, namely oral minocycline, due to safety concerns of all oral medications. the patient was placed on minocycline topical 4% foam, recently approved by the fda, for the course of one month. concluding her therapy, we observed a complete resolution of plaques with residual hyperpigmentation. in the literature, topical minocycline has been reported to treat more common dermatologic conditions, such as rosacea and acne vulgaris. to date, this is the first report on the usage of topical minocycline for the treatment of crp. introduction skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 61 antifungal treatment; and (v) an excellent response to oral minocycline.10,11 successful treatment of crp can be difficult, as lesions have been noted to recur months after treatment depending on the treatment modality.12 the preferred treatment of crp consists of oral minocycline, which has been shown to be the most effective against crp, 50-100 mg twice daily. minocycline, like all tetracyclines, works to prevent protein synthesis by attaching to the 30s ribosomal subunit in bacteria. minocycline also prevents the migration, and therefore the role of neutrophils in inflammatory processes. it possesses both antiinflammatory and immunomodulatory effects, but it’s unclear how these qualities treat atypical keratinization.9 however, minocycline as a preferred method of treatment comes with concerns of adverse effects such as drug toxicity, drug-induced lupus, and abnormal skin pigmentation at the site of pre-existing lesions.11 furthermore, minocycline is not recommended for use in pregnant women.9 of late, oral azithromycin has been proven to be effective in treating crp, and the medication is safe for use during pregnancy.13 other oral treatment methods for crp have been cited in the literature, including clarithromycin and erythromycin.14,15 topical treatments have been reported for use in the treatment of crp, including retinoids, tazarotene, urea, calcipotriol, and tacrolimus.16,17,18,19,20 a limitation in using topical treatment is the inability to reach the affected area for application, especially if crp is located on the back.11 recurrences have been reported with the use of antifungals such as ketoconazole, tolnaftate, and itraconazole.21 a recent systematic review of treatment outcomes in crp found that minocycline was the most frequently used tetracycline across the literature, achieving complete resolution in 61% of 114 cases and partial resolution in 21.1% of cases within 51.0 days. oral antibiotics such as amoxicillin and azithromycin were used in 26 cases, reaching complete resolution or partial resolution of crp within 57.9 days in 92.3% of cases. oral and topical antifungals fared poorly, with the majority of patients (62.5% of 56 cases) reporting no improvement in appearance. oral and topical retinoids resulted in complete or partial resolution in 73.3% of the 19 cases within 68.8 days. combination therapy with minocycline and other topical agents was used in 25 cases, 9 of which reached complete resolution (36%) and 8 of which reported no improvement (32%). adverse effects such as fatigue, gastrointestinal symptoms, and cheilitis were reported with combination therapies.22 further reviews have found the use of minocycline or azithromycin to yield positive results with a marked response, defined as a 50% improvement in appearance, against crp.11 overall, antibiotics such as oral minocycline have proven to be the most efficacious against crp. antibiotics that boast both antibacterial and anti-inflammatory properties, such as tetracyclines, yield the greatest results.9 future directions for the treatment of crp include topical minocycline. approved by the fda in 2019, minocycline topical 4% foam has been cited in the literature to treat acne vulgaris and rosacea.23 currently, there is no existing literature on the usage of topical minocycline for the treatment of crp. a 51-year-old african american woman with a past medical history of a rash for the past eight months presented with reticulated brown plaques overlying the midline of the case report skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 62 chest and extending underneath the inframammary folds (figure 1). figure 1. crp on the midline of the patients’ chest before treatment with minocycline topical 4% foam. crp was diagnosed clinically. the patient was reluctant to take oral antibiotics, namely oral minocycline, due to her concerns regarding the safety of all oral medications. the patient was prescribed minocycline topical 4% foam, to be applied once a day over the affected area for one month. follow-up with the patient approximately one month after her initial visit showed resolution of plaques with significant improvement (figure 2). on follow-up with the patient approximately 2 months after initial diagnosis, she reported that the rash cleared completely after one month of continuous application of topical medicine. two weeks after suspending use, the rash on her chest returned. she reports using the topical minocycline intermittently. the rash cleared within 4-5 days of use; however it recurred soon after stopping treatment. figure 2. after treatment with minocycline topical 4% foam. significant improvement with resolution of plaque and decreased hyperpigmentation. crp is a relatively rare dermatosis with unknown etiology. the chronic nature of crp is demonstrated by its recurrence rate with pharmacologic treatments other than monotherapy with oral minocycline, with antifungals, combination therapies, and retinoids either yielding poor results or lacking sufficient evidence due to study limitations (small sample sizes, uncontrolled trials).22 the most successful treatment in the literature to date is oral minocycline, 50 100 mg a day. however, there is increasing concern regarding bacterial resistance due to the overuse of antibiotics. although discussion skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 63 topical minocycline is still an antibiotic, the risks conferred with oral antibiotics for treatment of dermatoses are greater due to increased likelihood of systemic side effects, decreased concentration of antibiotic at the preferred site on skin, antibiotic resistance selection in gut microbiota, and generally less drug usage to achieve the desired effect.24 there is a generalized pervasive aversion to the utilization of oral medications in dermatology from the patient’s perspective, due in part to these factors. while further research is necessary on the topic, minocycline topical 4% foam offers a new alternative to long-term oral antibiotics in treating a recurrent, chronic disease. conflict of interest disclosures: none funding: none corresponding author: hanna lateef, bs 1115 w call st. tallahassee, fl 32304 phone: 407-376-5507 email: hl19l@fsu.edu references: 1. gougerot h, carteaud a. papillomatose pigmentée innominée. case pour diagnostic. bulletin de la société françiase de dermatologie et de syphiligraphie. 1927; 34: 712-719. 2. gougerot h, carteaud a. neue formen der papillomatose. archiv für dermatologie und syphilis. 1932; 165: 232-267. 3. wise f, sachs w. cutaneous papillomatose: papillomatose confluente et réticulée. arch dermatol syphilol. 1937; 36: 475-485. 4. wise f. confluent and reticulated papillomatosis (gougerot-carteaud). arch dermatol syphilol. 1937; 35: 550. 5. schwartz ra. confluent and reticulated papillomatosis. medscape. https://emedicine.medscape.com/article/1106748overview. published may 18, 2021. accessed august 8, 2021. 6. meischer vg. erythrokeratodermia papularis et reticularis. dermatologica. 1954; 108(4-6): 303309. 7. thomsen k. confluent and reticutared papillomatosis (gougerot-carteaud). acta derm venereol suppl (stockh). 1979; 59: 185-187. 8. kumar as, pandhi rk. syndrome of carteaud and gougerot case report. confluent and reticulate papillomatosis. mykosen 1984; 27: 313-315. 9. scheinfeld, n. confluent and reticulated papillomatosis: a review of the literature. am j clin dermatol. 2006; 7(5): 305-313. 10. davis mdp, weenig rh, camilleri mj. confluent and reticulated papillomatosis (gougerot-carteaud syndrome): a minocycline-responsive dermatosis without evidence for yeast in pathogenesis. a study of 39 patients and a proposal of diagnostic criteria. br j dermatol. 2006; 154(2): 287–93. 11. lim jhl, tet lh, chong w. confluent and reticulated papillomatosis: diagnostic and treatment challenges. clin cosmet investig dermatol. 2016; 9: 217–23. 12. angeli-besson c, koeppel mc, acquet pj, andrac l, sayag j. confluent and reticulated papillomatosis (gougerot-carteaud) treated with tetracyclines. int j dermatol. 1995; 34(8): 567569. 13. gruber e, zamolo g, saftic m, perhada v, kastelan m. treatment of confluent and reticulated papillomatosis with azithromycin. clin exp dermatol. 1998; 23(4): 191. 14. jang hs, oh ck, chat jh, cho sh, kwon ks. six cases of confluent and reticulated papillomatosis alleviated by various antibiotics. j am acad dermatol. 2001; 44(4): 652-655. 15. kim bs, lim hj, kim hy, lee wj, lee sj, kim do w. case of minocycline-effective confluent and reticulated papillomatosis with unusual location on forehead. j dermatol. 2009; 36(4): 251-253. 16. kagi mk, trueb r, wuthrich b, burg g. confluent and reticulated papillomatosis associated with atopy. successful treatment with topical urea and tretinoin. br j dermatol. 1996; 134(2): 381–382. 17. bowman ph, davis ls. confluent and reticulated papillomatosis: response to tazarotene. j am acad dermatol. 2003; 48(5 suppl): s80–s581. 18. gulec at, seckin d. confluent and reticulated papillomatosis: treatment with topical calcipotriol. br j dermatol. 1999; 141(6): 1150–1151. 19. kurkeuoglu n, celebi cr. confluent and reticulated papillomatosis: response to topical calcipotriol. dermatol. 1995; 191(4): 341–342. 20. tirado-sánchez a, ponce-olivera rm. tacrolimus in confluent and reticulated conclusion mailto:hl19l@fsu.edu skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 64 papillomatosis of gougerot carteaud. int j dermatol. 2013; 52(4): 513–514. 21. nordby ca, mitchell aj. confluent and reticulated papillomatosis responsive to selenium sulfide. int j dermatol. 1986; 25(3): 194-199. 22. mufti, a., sachdeva, m., maliyar, k., lansang, r. p., lytvyn, y., sibbald, r. g., & yeung, j. (2021). treatment outcomes in confluent and reticulated papillomatosis: a systematic review. journal of the american academy of dermatology, 84(3), 825– 829. 23. onge es, mobley wc. minocycline topical foam: a new drug for the treatment of acne. ann pharmacother. 2021 jan; 55(1): 105-110. 24. eady ea, cove jh. topical antibiotic therapy: current status and future prospects. drugs exp clin res. 1990; 16(8): 423-33. acknowledgements: medical writing support was provided by prescott medical communications group (chicago, il) with financial support from ortho dermatologics; ortho dermatologics is a division of bausch health us, llc • presented at fall clinical dermatology conference • october 21-24, 2021 • las vegas, nv conclusions � nearly three-fourths of all participants treated with tazarotene 0.045% lotion—including black participants—had subjective reductions in skin oiliness by week 12, with over a third reporting low/not oily skin � it is possible the improvements in oiliness observed with tazarotene lotion were due to the unique, non-greasy excipients/emulsifiers contained in the polymeric emulsion lotion vehicle; this emulsion technology provides fast, uniform, and complete release of the humectants, oil droplets, and other excipients contained in the vehicle onto the skin9 � tazarotene lotion also demonstrated efficacy and safety in the treatment of moderate-tosevere acne in participants with oily skin, with rates similar to the overall population � once-daily treatment with tazarotene 0.045% lotion may help improve patient-perceived skin oiliness in those with moderate-to-severe acne synopsis � excessive sebum production is a factor in facial acne development1 and oily skin is a frequent complaint of dermatology patients with or without acne2 • larger pore sizes may be associated with higher rates of sebum production3 • skin oiliness and pore size can also differ by race, with larger amounts of sebum secretion and larger pore sizes observed in black patients2,4 � topical retinoids are a mainstay of acne treatment, though they are associated with cutaneous irritation, which may limit their use5 • as vehicles formulated with emollients/moisturizers may reduce retinoid-associated irritation,5 it is possible that naturally oily skin may also provide a protective effect � though its effects on sebum production are unknown, the topical retinoid, tazarotene 0.1% cream, has been shown to reduce apparent facial pore size6 � the lower-dose 0.045% tazarotene polymeric lotion has also demonstrated efficacy in reducing acne lesions and acne-induced sequalae such as hyperpigmentation with good tolerability and safety profiles7 objective � to evaluate efficacy, changes in skin oiliness, and safety/tolerability with tazarotene 0.045% lotion in participants with acne and oily skin, including black participants methods � in two phase 3, double-blind, 12-week studies (nct03168334; nct03168321), participants aged ≥9 years with moderate-to-severe acne were randomized 1:1 to once-daily tazarotene 0.045% lotion or vehicle lotion • cerave® hydrating cleanser and cerave® moisturizing lotion (l’oreal, ny) were provided as needed for optimal moisturization/cleaning of the skin � this pooled, post hoc analysis comprised participants categorized by self-reported skin oiliness at baseline on the acne-specific quality of life questionnaire item 198 • scored from 0 (extremely oily) to 6 (not at all oily; figure 1) • only participants scoring 0–2 (oily skin) were included in this analysis � coprimary endpoints were inflammatory/noninflammatory lesion counts and treatment success (≥2-grade reduction from baseline in evaluator’s global severity score [egss] and a score of 0 [clear] or 1 [almost clear]) � changes in skin oiliness, treatment-emergent adverse events (teaes), and cutaneous safety and tolerability were also evaluated • a subset of participants with oily skin who self-reported race as black were also analyzed for changes in skin oiliness and cutaneous safety and tolerability figure 1. oily skin assessment 19. in the past week, how oily was your facial skin? extremely 0 very much 1 quite a bit 2 a good bit 3 somewhat 4 a little bit 5 not at all 6score= oily skin moderately oily skin low/not oily skin baseline responses on the acne-specific quality of life questionnaire item 19 were used to categorize participants into 3 groups: oily, moderately oily, and low/not oily skin. figure 3. improvements in oily skin from baseline to week 12 (itt population) 80% 0% 20% 40% 60% shift to “moderately” or “low/not” oily skin p e rc e n ta g e o f p a rt ic ip a n ts 100% all participants with oily skin 0-2  3, 4, 5, or 6 71.4% shift to “low/not” oily skin 0-2  5 or 6 28.6% 35.0% veh (n=318) taz (n=311) 80% 0% 20% 40% 60% shift to “moderately” or “low/not” oily skin 100% black participants with oily skin 0-2  3, 4, 5, or 6 67.6% 81.4% shift to “low/not” oily skin 0-2  5 or 6 32.4% 37.3% veh (n=68) taz (n=59) 71.1% categories based on acne-quality of life questionnaire item 19 scores at baseline: low/not oily (score=5 to 6); moderately oily (score=3 to 4); oily (score=0 to 2; see figure 1). no imputation of missing data. n values indicate participants with “oily” skin at baseline who also had data at week 12. itt, intent to treat; taz, tazarotene 0.045% lotion; veh, vehicle lotion. safety and tolerability � teae rates with tazarotene in all oily-skin patients (n=359; safety population) were similar to those observed in the overall tazarotene-treated population (n=779; safety population)7 (any teae: 27.9% vs 26.8%; treatment-related teae: 11.7% vs 11.3%, respectively) � the percentage of tazarotene-treated oily skin participants reporting “none” on cutaneous safety and tolerability assessments at week 12 was generally similar to baseline values for most assessments (figure 4) • as expected, transient increases in mild-to-moderate itching, burning, stinging, scaling, and erythema were observed (data not shown) � similar trends were observed in black participants with oily skin (tazarotene n=70, vehicle n=75; safety population), though black participants had greater improvements in hyperpigmentation and fewer reports of erythema and scaling at week 12 (figure 4) improvements in acne and skin oiliness with tazarotene 0.045% lotion in acne patients with oily skin emil a tanghetti, md1; michael gold, md2; neil sadick, md3,4; fran e cook-bolden, md4,5; leon h kircik, md6-8; linda stein gold, md9; stephen k tyring, md10; james q del rosso, do11; eric guenin, pharmd, phd, mph12 1center for dermatology and laser surgery, sacramento, ca; 2tennessee clinical research center, nashville, tn; 3sadick dermatology, new york, ny; 4weill cornell medical college, new york, ny; 5fran e. cook-bolden, md, pllc; 6indiana university school of medicine, indianapolis, in; 7physicians skin care, pllc, louisville, ky; 8icahn school of medicine at mount sinai, new york, ny; 9henry ford hospital, detroit, mi; 10university of texas health science center, houston, tx; 11jdr dermatology research/thomas dermatology, las vegas, nv; 12ortho dermatologics,* bridgewater, nj *ortho dermatologics is a division of bausch health us, llc results demographics and baseline characteristics � of 1614 participants in the intent to treat population (itt) of the two pooled phase 3 studies, 736 had oily skin (45.6%) • they had a mean age of 21.6 years, 73% were female, and 69% were white • approximately 90% had moderate egss at baseline � of 261 participants who identified as black (itt population), 150 had oily skin (57.4%) • they were slightly older (mean age 25.2 years), and a greater percentage were female (82.7%) • most had moderate egss at baseline (94.7%) efficacy � in all participants with oily skin, tazarotene 0.045% lotion provided significantly greater least-squares mean percent reduction from baseline to week 12 in inflammatory and noninflammatory lesion counts vs vehicle (p<0.001, both; figure 2) � treatment success rates at week 12 were significantly higher for all tazarotenetreated participants vs vehicle (29.8% vs 19.2%; p<0.01) • these results are similar to those in the overall phase 3 pooled population for lesion reductions (see figure 2 footnote) and treatment success rates at week 12 (30.4% tazarotene and 17.9% vehicle; p<0.0017) figure 2. reduc tions in acne lesion counts by visit in all participants with oily skin (itt population) in�ammatory -29.7% -40.2% -48.4% -28.9% -48.0% -57.0% -70% -60% -50% -40% -30% -20% -10% 0% baseline week 4 week 8 week 12 veh (n=367) taz (n=369) ** ls m e a n c h a n g e f ro m b a se lin e *** nonin�ammatory -25.6% -32.6% -42.1%-32.5% -48.1% -55.9% baseline week 4 week 8 week 12 veh (n=367) taz (n=369) *** *** ** -70% -60% -50% -40% -30% -20% -10% 0% **p<0.01; ***p<0.001 vs vehicle. multiple imputation used to impute missing values. overall phase 3 pooled population at week 12: inflammatory taz -57.9% and veh -47.8%; noninflammatory taz -56.0% and veh -42.0%; p<0.001, both.7 itt, intent to treat; ls, least squares; taz, tazarotene 0.045% lotion; veh, vehicle lotion. skin oiliness � most participants reported an improvement in skin oiliness to “moderately” or “low/not” oily with tazarotene 0.045% and vehicle; numerically more participants reported an improvement to “low/not” oily skin with tazarotene than vehicle (figure 3) � most black participants with oily skin also reported an improvement in skin oiliness to “moderately” or “low/not” oily with tazarotene and vehicle, with a numerically greater percentage in the tazarotene-treated group (figure 3) figure 4. cutaneous safety and tolerability (safety population) 30% 70% 50% 10% 90% p e rc e n ta g e o f p a rt ic ip a n ts 0% 40% 80% all participants with oily skin taz veh baseline: mild moderate severe week 12: mild moderate severe scaling 60% 20% 100% taz veh erythema taz veh hypopigmentation taz veh hyperpigmentation taz veh itching taz veh burning taz veh stinging investigator-assessed participant-assessed 30% 70% 50% 10% 90% p e rc e n ta g e o f p a rt ic ip a n ts 0% 40% 80% black participants with oily skin taz veh baseline: mild moderate severe week 12: mild moderate severe scaling 60% 20% 100% taz veh erythema taz veh hypopigmentation taz veh hyperpigmentation taz veh itching taz veh burning taz veh stinging investigator-assessed participant-assessed no imputation of missing data. n values: all participants with oily skin baseline: taz n=359, veh, n=353; week 12: taz n=312, veh n=318; black participants with oily skin baseline: taz n=70, veh n=75; week 12: taz n=59, veh n=68. taz, tazarotene 0.045% lotion; veh, vehicle lotion. references 1. moradi tuchayi s, et al. nat rev dis primers. 2015;1:15029. 2. endly dc, et al. j clin aesthet dermatol. 2017;10(8):49-55. 3. roh m, et al. br j dermatol. 2006;155(5):890-894. 4. pappas a, et al. dermatoendocrinol. 2013;5(2):319-324. 5. leyden j, et al. dermatol ther (heidelb). 2017;7(3):293-304. 6. kang s, et al. j am acad dermatol. 2005;52(2):268-274. 7. tanghetti ea, et al. j drugs dermatol. 2020;19(3):272-279. 8. martin ar, et al. clin exp dermatol. 2001;26(5):380-385. 9. tanghetti ea, et al. j dermatol treat. 2021;32(4):391-398 author disclosures emil a tanghetti has served as speaker for novartis, ortho dermatologics, sun pharma, lilly, galderma, abbvie, and dermira; served as a consultant/clinical studies for hologic, ortho dermatologics, and galderma; and is a stockholder for accure. michael gold has acted as an investigator, advisor, speaker, and consultant for ortho dermatologics. neil sadick has served on advisory boards, as a consultant, investigator, speaker, and/or other and has received honoraria and/or grants/research funding from almirall, actavis, allergan, anacor pharmaceuticals, auxilium pharmaceuticals, bausch health, bayer, biorasi, btg, carma laboratories, cassiopea, celgene corporation, cutera, cynosure, dusa pharmaceuticals, eclipse medical, eli lilly and company, endo international, endymed medical, ferndale laboratories, galderma, gerson lehrman group, hydropeptide, merz aesthetics, neostrata, novartis, nutraceutical wellness, palomar medical technologies, prescriber’s choice, regeneron, roche laboratories, samumed, solta medical, storz medical ag, suneva medical, vanda pharmaceuticals, and venus concept. fran e cook-bolden has served as consultant, speaker, investigator for galderma, leo pharma, almirall, cassiopea, ortho dermatologics, investigators encore, foamix, hovione, aclaris, cutanea. leon h kircik has acted as an investigator, advisor, speaker, and consultant for ortho dermatologics. linda stein gold has served as investigator/consultant or speaker for ortho dermatologics, leo pharma, dermavant, incyte, novartis, abbvie, pfizer, sun pharma, ucb, arcutis and lilly. stephen k tyring is has acted as an investigator for ortho dermatologics. james q del rosso has served as a consultant, investigator, and/or speaker for ortho dermatologics, abbvie, amgen, arcutis, dermavant, epi heath, galderma, incyte, leo pharma, lilly, mc2 therapeutics, pfizer, sun pharma, and ucb. eric guenin is an employee of ortho dermatologics and may hold stock and/or stock options in its parent company. 42x90 powerpoint presentation research poster presentation design © 2019 www.posterpresentations.com introduction mechanism of action • cysteamine is an aminothiol naturally present in human body cells as an antioxidant resulting from the degradation of coenzyme a.1 • cysteamine hydrochloride is known for its potent depigmenting effect since 1960's when chavin tested it through injecting cysteamine into the black goldfish skin.2 other in vitro and animal in vivo studies showed the higher depigmenting efficacy of this cysteamine compared to hydroquinone.3-5 • however, rapid oxidation and very offensive odor made it difficult for topical use.6 • an innovative technology has now been released to stabilize and deodorize cysteamine. cysteamine thus became utilizable for the first time in a topical product.7 • stabilized cysteamine has demonstrated significant effectiveness for the treatment of melasma by two double-blind randomized and vehicle control clinical studies, showing both greater reduction in mmasi score and melanin index compared to placebo.78 references 1. gallego-villar (2017). cysteamine revisited: repair of arginine to cysteine mutations. j. inherit. metab. dis., 40(4), 555-567. 2. chavin, w.; schlesinger, w. (1966). some potent melanin depigmentary agents in the black goldfish. die naturwissenschaften 53(16): 413–414. 3. frenk e, pathak ma, szabo g, fitzpatrick tb. (1968). selective action of mercaptoethylamines on melanocytes in mammalian skin: experimental depigmentation. arch dermatol 97:465–77. 4. bleehen, s. s., pathak, m. a., hori, y., & fitzpatrick, t. b. (1968). depigmentation of skin with 4-isopropylcatechol, mercaptoamines, and other compounds. j invest dermatol, 50(2), 103-117. 5. qiu l, zhang m, sturm ra, gardiner b, tonks i, kay g, parsons pg. (2000) inhibition of melanin synthesis by cysteamine in human melanoma cells. j invest dermatol. 114(1):21-7. 6. atallah, c., charcosset, c., & greige-gerges, h. (2020). challenges for cysteamine stabilization, quantification, and biological effects improvement. j pharm anal. 7. mansouri, p.; farshi, s.; hashemi, z.; kasraee, b. (2015).evaluation of the efficacy of cysteamine 5% cream in the treatment of epidermal melasma: a randomized double-blind placebo-controlled trial. br j dermatol. 173 (1): 209–217. 8. farshi, and al. (2017).efficacy of cysteamine cream in the treatment of epidermal melasma, evaluating by dermacatch as a new measurement method: a randomized double-blind placebo-controlled study. j dermatol treat, 1–8. 9. wood, j. m., & schallreuter, k. u. (1991). studies on the reactions between human tyrosinase, superoxide anion, hydrogen peroxide and thiols. biochim biophys acta, 1074(3), 378-385. 10. sakurai, h.; yokoyama, a.; tanaka, h. (1971). studies on the sulfur-containing chelating agents. xxxi. catalytic effect of copper (ii) ion to formation of mixed disulfide. chem. pharm. bull. 19, 1416–1423 11. bottu, g. (1989). the effect of quenchers on the chemiluminescence of luminol and lucigenin. j biolumin chemilumin. 12. crinelli, rita, et al. (2019). boosting gsh using the co-drug approach: i-152, a conjugate of n-acetyl-cysteine and βmercaptoethylamine. nutrients 11.6 1291. 13. publication pending 14. karrabi, m., and al. (2020). clinical evaluation of efficacy, safety and tolerability of cysteamine 5% cream in comparison with modified kligman’s formula in subjects with epidermal melasma: a randomized, double‐blind clinical trial study. skin res and technology 15. karrabi, m., and al. (2020). clinical evaluation of efficacy and tolerability of cysteamine 5% cream in comparison with tranexamic acid mesotherapy in subjects with melasma: a single-blind, randomized clinical trial study. arch of dermatol res. 16. nguyen, j & rodrigues, m. (2021). evaluation of the efficacy of cysteamine cream compared to hydroquinone in the treatment of melasma: a randomised, double‐blinded trial. aus j dermatol, 62(1), e41-e46. seemal r. desai, md faad director and founder: innovative dermatology clinical assistant professor of dermatology: university of texas southwestern cysteamine: clinical efficacy, safety and tolerability versus best-in-class treatments for melasma cysteamine has a broad action in the regulation of melanogenesis: • enzymatic effect: inhibition of tyrosinase and peroxidase, essential enzymes in the melanogenesis pathway leading to the conversion of tyrosine into dopaquinone, and to the polymerization of indoles into melanin.9 • chemical effect: chelation of mineral ions, preventing fenton-type reactions.10 • antioxidant & quencher of free radicals: suppression of all the oxidation steps in the melanogenesis process & prevention of photo-oxidation (ie darkening of melanin precursors in the epidermis). 11 • cascade reaction: increase of intracellular glutathione, amplifying natural depigmenting effects.12 • keratolytic effect: by breaking keratin disulfide bonds, it enhances the removal of melanin contained in the superficial epidermis layers and accelerates the epidermal turnover for generation of new non-pigmented skin layers.13 5% stabilized cysteamine (st-cys-5%) versus modified kligman’s formula (mkf)14 material and methods double-blinded, investigator-driven, randomized 50 female with melasma, 20-50 years old, assigned in 2 groups: •st-cys-5% 15min application + moisturizer + sunscreen (daily, 16weeks) •mkf overnight application (4% hydroquinone, 0.05% retinoic acid and 0.1% betamethasone) + moisturizer + sunscreen (daily, 16 weeks) evaluation of mmasi score; investigator global assesment & patient questionnaires evaluation at baseline, 8 weeks and 16 weeks efficacity results at both week 8 and week 16, st-cys-5% produced significantly greater reductions from baseline in modified melasma area severity index (mmasi) (32.3%, 51.3%), compared to mkf (23.7%, 42.3%; p = .005 and .001, respectively). investigator global assessment and patient self-assessment scores were similar for both treatments at each time-point. safety & tolerability results in all and at 16 weeks, 64% of patients treated with st-cys-5% reported no skin irritation, whereas only 8% of patients treated with mkf reported no skin irritation. 5% stabilized cysteamine (st-cys-5%) versus tranexamic acid mesotherapy (txa)15 material and methods single-blinded, investigator-driven, randomized 54 female with melasma, 18-50 years old, assigned in 2 groups: •st-cys-5% 30min application (daily, 16weeks) •txa 0.05ml (4mg/ml) administered mesotherapy (every 4 weeks for 8 weeks) evaluation of mmasi score and melanin index evaluation at baseline, 8 weeks and 16 weeks for group st-cys-5% evaluation at baseline, 4 weeks and 8 weeks for group txa efficacity results the degree of improvement of mmasi reduction was 45.9% for st-cys-5% after 16 weeks and 47.1% for multiple sessions of txa mesotherapy. no patient in either group had recurrence of melasma in the follow-up period. in both group and at both visits, melanin index measured by dermacatch was equally reduced (p>0.1). safety & tolerability results complications were significantly more frequent in the txa group. -27.4% -45.9% -32.6% -47.1% -50.0% -40.0% -30.0% -20.0% -10.0% 0.0% stabilized cysteamine (cyspera® scientis sa) txa mesotherapy 5% stabilized cysteamine (st-cys-5%) versus hydroquinone 5% (hq)16 material and methods double-blinded, investigator-driven, randomized 20 female with melasma, >18 years old, assigned in 2 groups : •st-cys-5% 15min application + moisturizer + sunscreen (daily, 16weeks) •moisturizer + hq4% + sunscreens (daily 16weeks) evaluation of mmasi score & quality of life (qol) questionnaire evaluation at baseline, 8 weeks and 16 weeks efficacity results various limitations for this study due to large number of drop out in both groups and small number of volunteer initially recruited (n= 9 in hq group, n=5 in st-cys group) at week 16, st-cys-5% was shown to be slightly superior in masi score reduction compared to hq4% when analyzed as per protocol (-39.1% versus -33%, p=0.96) at week 16, qol was slightly improved in both group, but not in a significant way conclusion : stabilized topical cysteamine was proven to be significatively more effective for the treatment of melasma and better tolerated than the modified kligman’s formula. when compared to hydroquinone and physician administered mesotherapy tranexamic acid (txa), stabilized cysteamine was shown to be as effective and better tolerated. according to these results, cysteamine can be considered the first line non-hydroquinone treatment for melasma. comparison of evolution in mmasi score versus baseline -60.0% -50.0% -40.0% -30.0% -20.0% -10.0% 0.0% -32.3% -51.3% -23.7% 42.3% stabilized cysteamine (cyspera® scientis sa) modified kligman formula visit 1 (8 weeks) visit 2 (16 weeks) sig. superior mmasi score reduction at 2 and 4 months none mild moderate severe comparison of the severity of adverse events observed after 16weeks (irritation) stabilized cysteamine modified kligman formula 92% irritation with mkf incl. 12% severe cases comparison of evolution in mmasi score versus baseline visit 1 (8 weeks for st-cys, 4weeks for txa) visit 2 (16 weeks for st-cys, 8 weeks for txa) comparable mmasi score reduction none mild moderate severe stabilized cysteamine (cyspera® scientis sa) txa mesotherapy comparison of the severity of adverse events observed at end of treatment (irritation) -19.7% -39.1%-39.2% -33.0% -50.0% -40.0% -30.0% -20.0% -10.0% 0.0% stabilized cysteamine (cyspera® scientis sa) hydroquinone 4% visit 1 (8 weeks) visit 2 (16 weeks) 100% of patients shows signs of irritation * (p value = 0.005) *** (p value = 0.001) *** (p value < 0.001) *** (p value < 0.001) comparable mmasi score reduction skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 130 resident competition research articles clear cell squamous cell carcinoma: clinical and histologic parameters and a review of the literature mathew loesch, do phd1, stephen j. ganocy, phd2, christine jaworsky, md3 1dupage medical group department of dermatology 2case western reserve university departments of psychiatry and population and quantitative health sciences 3case western reserve university department of dermatology metrohealth medical center scc is the second most common type of non-melanoma skin cancer, of which several histological subtypes have been described.1 one of these subtypes, the ccscc, is an uncommon variant with relatively few case reports and studies found in the literature. such lesions have been described clinically as nodules or ulcerated masses that can introduction background: clear cell squamous cell carcinoma (ccscc) is an uncommon subtype of squamous cell carcinoma. this tumor subtype arises more commonly in elderly individuals and occurring greater upon sun-exposed areas of the body. objective: to determine the age range and locations of ccscc, and occurrence in men as compared with women. methods: an observational study of ccscc accessioned at a dermatopathology laboratory (cleveland skin pathology, csp) over an 18-month interval. cases were retrieved and included based on a search of the terms “clear cell squamous cell carcinoma” in the diagnosis field of the csp database and reviewed for accuracy and the degree of clear cell change in each lesion. pathology requisition forms from these cases were used only to identify patients’ age, gender, and anatomic region of the ccscc reviewed. results: of the 17,838 cases of in situ and invasive scc, there were a total of 107 ccscc, 77 in situ and 30 invasive (0.6% of total scc). of patients with ccscc, 71% had a history of skin cancer, many (57.9%) in the same anatomic region. when the degree of clear cell change was evaluated there was no statistically significant increase of percentage clear cell change in tumors with age. conclusions: along with confirming past observations made with previous studies, our series shows that more men than women develop such tumors before 70 years of age, and more women than men after 70 years of age with men developing ccscc on average 7 years earlier than women. abstract skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 131 resemble various benign and malignant cutaneous neoplasms including metastatic renal cell carcinoma.1,2,3 ccscc have been noted to occur more frequently on the head and neck, with a nearly equal incidence in men and women.4 the initial report of this scc subtype by kuo in 1980 describes 6 cases primarily found on the head and neck of older males with known histories of excessive sun exposure.5 kuo further classified these 6 cases of ccscc into three major histologic types: keratinizing, non-keratinizing, and pleomorphic with no evidence of either glycogen or mucin present within these tumor cells cases.5 later studies have described mixed histological observations suggesting ccscc having either outer root sheath, trichilemmal or even viral origin but none of these studies have been definitive in their findings.6-9 the focus in the limited number of studies examining ccscc has been more on the immunohistochemical markers present as well as the histological patterns found with these lesions. the purpose of this study was to focus on the relationship this type of scc has to age, gender, and anatomic region and also to evaluate the degree of clear cell change in lesions with respect to age and clinical distribution of ccscc. data source and case selection all cases of in situ and invasive scc (17,838 cases in total) were collected and reviewed at csp over an 18-month interval (1/20166/2018). cases were included based on search of the terms “clear cell squamous cell carcinoma” in the diagnosis field of the csp database. all ccscc cases included were evaluated by one dermatopathologist (cj) for this study. once the ccscc diagnosis was verified, the patients’ records were checked to ensure that the same tumor was not counted twice for this study. an example of this is counting an initial ccscc biopsy and not the later excision of a same ccscc from an individual. clear cell change was defined in this study as those cells that possessed clear appearing cytoplasm within the scc on h&e (figure 1). the ccscc were then graded on percentage of clear cell change ranging from less than 20%, 20-40%, 4060%, 60-80% and greater than 80%. follicular adnexal involvement by tumor within the ccscc lesion was also noted. case and patient characteristics present on the pathology requisition forms were used only to identify age, gender, and anatomic region of the ccscc lesion biopsied as well as to review the other skin cancers biopsied and read at csp from the same ccscc positive individual. this study was approved by the internal review board at kansas city university of medicine and biosciences. statistical analysis analysis of the ccscc cases was completed using microsoft excel software. frequency and relative frequency distribution diagrams were used to analyze this case population for the following criteria: 1) occurrence of total cutaneous ccscc in the age ranges describe previously, 2) percentage level of clear cell change within ccscc lesions over the designated age ranges, and 3) percentage of clear cell change within ccscc by anatomic site. chi-squared analysis was used to determine the significance of the proportion of age less than 70 years and above 70 years with respect to gender. student’s two-sample t-test was used to determine significance between average age of diagnosis between gender groups. methods skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 132 figure 1. photomicrographs of both ccscc/ccsccis and non-ccscc/non-ccsccis lesions. a: squamous cell carcinoma in situ without clear cell change (200x) contrasted with b: clear cell squamous cell carcinoma in situ (200x); c: adnexal extension of clear cell sccis; d: invasive scc without clear cell change (100x) contrasted with e: invasive clear cell scc (100x). hematoxylin-eosin stain used for a-e. all cases of scc (7,591) and sccis (10,247) were read between the dates of 1/20166/2018 at csp. of these cases, only 107 had clear cell change (30 invasive scc and 77 ccscc in situ) representing 0.6% of the total scc cases read at csp. the cases of ccscc demonstrated a relatively even distribution between males and females (57:50) and an overall mean age of roughly 74.9 years old at time of biopsy. of these ccscc cases, 71% of these individuals had a history of other skin cancers in addition to their ccscc, with 57.9% of these patients having their additional skin cancer in the same anatomic region as their ccscc. nearly half of all ccscc (49.5%) showed tumoral extension into follicular adnexa. history of additional skin cancers and their anatomic locations in ccscc positive individuals was also tabulated from data available in csp’s database. the relative frequency analysis demonstrates that in those who have had a ccscc and a history of other skin cancers, non-ccscc was the most common (69.5%) followed by bcc (27.4%) (table i). these additional skin cancers were also more likely to arise in same anatomic region as their ccscc, with the head and neck region (56.5%) being the most frequent for this to occur. age differences among males and females diagnosed with ccscc were examined in those who were less than 70 years of age and those greater than 70 years of age. from this analysis using chi-squared testing, there was a statistically significant greater proportion of males diagnosed with ccscc (43.9%) than females (18.0%) less than 70 years old in this sample (p=0.0042) (table ii). from this sample of ccscc cases, the average age at diagnosis for ccscc was 7 years earlier for males than for females, a difference that was also statistically significant (71.7 years for results skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 133 males vs. 78.7 years for females, p=0.003) (table ii). two-way frequency analysis was used to examine the relationship trends of clear cell change within these ccscc cases by age bracket as well as by the anatomic origin of the ccscc lesion (figure 2a&b). in these observational analyses, the degree of clear cell change increased as the bracketed age range increased, peaking at 60-80% clear cell change in lesions seen between ages 70-80 (n=14, 14.1%) and 80-90 (n=13, 13.1%) years old before dropping off. there was no statistical significance of % clear cell change with age. in the analysis examining the degree of clear cell change by anatomic region, the largest percentage of clear cell change was seen on the head and neck compared to all other anatomic regions seen around the 4060% (n=15, 15.2%) and 60-80% (n=25, 25.3%) clear cell change ranges. figure 2. analysis of percent level of clear cell change of these ccscc cases. a, frequency histogram of percent clear cell change within ccsccs cases by age bracket. b, frequency histogram of percent clear cell change within ccsccs cases by anatomic location. ccscc, clear cell squamous cell carcinoma; ext, extremity. table i. breakdown of total sccs reviewed at csp and characteristics of the individuals with cases of ccscc lesions in this study. ccscc, clear cell squamous cell carcinoma. scc case breakdown of between january 2016june 2018 reviewed at csp (n) (%) total scc (%) 17838 100% sccis (%) 10247 57.4% invasive scc (%) 7591 42.6% total number of clear cell scc (%) 107 0.60% clear cell sccis (%) 77 0.43% invasive clear cell scc (%) 30 0.17% characteristics of the individuals with cases of clear cell scc lesions males (%) 57 53.3% females (%) 50 46.7% median age of those with ccscc (min,max) 76.9 36.7, 97.6 those with history of having skin cancer other than ccscc (%) 76 71.0% breakdown of total and type of these other skin cancers total number skin cancers known in these individuals (%) 420 100% with history of scc (%) 292 69.5% skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 134 with history of bcc (%) 115 27.4% with history of melanoma (%) 5 1.2% with history of adnexal neoplasm (%) 3 0.7% with history of other skin cancers (%) 5 1.2% those having ccscc within same anatomic region as their history of other skin cancer 62 57.9% breakdown distribution frequency by these same anatomic regions head/neck (%) 35 56.5% chest (%) 4 6.5% back (%) 4 6.5% upper extremities (%) 9 14.5% lower extremities (%) 10 16.1% follicular adnexal involvement in the lesion (%) 53 49.5% table ii. proportion male verse female cases of ccscc less than or great than 70 year of age and age of diagnosis between genders. proportion male verse female cases of ccscc less than or great than 70 year of age age group males (n=57) % females (n=50) % chi-square p-value less than 70 yr 25 43.9 9 18.0 8.22 0.0042 greater than 70 yr 32 56.1 41 82.0 age at time of ccscc diagnosis between genders sex n mean stddev stderr t p-value males 57 71.7 13.3 1.8 3.04 0.0030 females 50 78.7 10.1 1.4 ccscc is an uncommon form of cutaneous scc related to advanced age and chronic uv radiation exposure. our findings are consistent with prior reports that the majority of patients with ccscc are elderly individuals, with an average age 74.9 years, and that such tumors are found more frequently on the head and neck than at other anatomic sites (table i).4 in addition, this study was able to determine with significance that before the age of 70, men are more likely to be diagnosed with ccscc than women and that the average age at diagnosis for ccscc was 7 years earlier for males than for females (table ii). the degree of clear cell change relative to age and anatomic location demonstrates observationally as age increases; the level of clear cell change present in the ccscc lesion is greater (figure 2b). this is also true for those areas that are more photo-exposed, thus having prolonged uv exposure resulting in photo-damage such as that directed onto the head and neck region showed the greatest amount of clear cell change in this analysis. together these findings are congruent with those in other ccscc studies.4,6,8 in our study, the most commonly discussion skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 135 affected sites in both genders were the head and neck. the next most commonly affected sites were the upper trunk and upper extremities in men, and the lower extremities in women. this study showed that a large percentage of individuals with ccscc also had a history of another skin cancer (71%) with non-ccscc and bcc being the largest other skin cancers most frequently observed in these patients (table i). these were separate skin cancers which were also read at csp in addition to the ccscc cases with careful consideration to not include any duplicate pathology. most patients, 57.9%, had additional skin cancer(s) in the same anatomic location as their ccscc, with the head and neck being the most frequent tumor locations. these observations underscore the role of chronic uv exposure in connection to ccscc in attaining a threshold of actinic damage for the development of a non-ccscc and bcc nearby. of interest, there were two relatively younger patients with ccsccis in this study, 36 and 38 years old. the 36 year old had a prior history of invasive melanoma, 3 basal cell carcinomas, and multiple dysplastic nevi. no additional history was available for the 38 year old individual. the significance of the follicular adnexal involvement remains to be fully understood. some studies suggest ccscc has outer root sheath or trichilemmal origin, however, observational interpretations have been mixed.3,5 al-arashi et al found that some in situ lesions of ccscc stain positive for pas and immunohistochemical markers ck8.12, cam 5.2, and ck15 suggesting outer root sheath (ors) differentiation.4 misago et al confirmed that ors markers are retained in trichilemmomas (ck17, cd34, d2-40), but did not find clear immunohistochemical evidence of trichilemmal differentiation in ccscc.6 lastly, dalton and leboit also reviewed cases of clear cell carcinoma of the skin comparing cases to trichilemmomas with cd34, ck17, and ngfr/p75 to assess ors differentiation. of the cases they stained, all tumors were positive for ck17 but only 2 cases stained with cd34 or ngfr/p75, indicating that ccscc does not show trichilemmal differentiation.7 separately, corbalan-velez et al described two histologic patterns in the sccs with clear-cell changes in their reported cases. first was a pattern with clear-cells around keratin pearls more commonly found with prior actinic keratosis (ak) and what they believed to be indirect signs of hpv within the infundibulum of lesions. the second pattern observed resembled adnexal differentiation associated with prior bowens disease.8 cohen at al reported two cases of facial ccsccis, both on the cheeks of an elderly husband and wife. each had a ccsccis with hpv present, however, one contained hpv 5 and the other hpv 21, respectively, suggesting that hpv dna may be a factor in the development of ccscc.9 clear cell change may arise for various reasons and its etiology remains uncertain, as a review of the literature (table iii) indicates. skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 136 table iii. literature review and summary of prior ccscc studies. ccscc, clear cell squamous cell carcinoma. ccscc, clear cell squamous cell carcinoma; n/d, not done study cases gender age pas pas with diastase immuno peroxida se ors by immunop eroxidase hpv summary/ miscellaneous findings kuo t (5) 6 6 m 5280 n/d n/d n/d n/d negative oil red o stains lawal ao et al (1) 1 m 62 n/d ae1/ae3 + n/d n/d al-arashi my, byers hr (4) 80 n/d n/d + n/d ck 7,10,18,1 9; neg ck15 pos in 50% 14/80 cases stained, and were + n/d clear cell change in sccis is part of the spectrum which displays ors differentiation cohen pr et al (9) 2 1 m, 1 f 80 n/d n/d n/d + consort sccis containing hpv in clear cells of facial lesions of an octogenarian couple corbalanvelez r et al (8) 122 not stated avg. 73.4 + n/d cd34,e ma, cea n/d analysi s not possibl e suggestive of adnexal differentiation dalton sr, leboit pe (7) 40 29 m, 11 f 5691 95% + 95% + cd34,ck 17, ngfr/p7 5 85% negative for ors markers n/d welldifferentiated trichilemmal carcinoma is rare misago n, et al (6) 10 3 m, 7 f 6590 varia ble variable ck1,ck1 0,ck17, cd34, d2-40 n/d no clear immunohistoch enical evidence of trichilemmal differentiation in ccscc requena l et al (3) 1 m 62 not in clear cells n/d high/low molecula r weight cytokerati ns + n/d n/d electron microscopy saw vacuoles without lipid in this study, the percentage of specimens that showed follicular involvement with ccscc lesions (table i) was 49.5%, and reflects sampling of the tumors in routine sections. whether this indicates tumor extension to be associated with relative epidermal atrophy, or with aging and exposure of follicular ostia to oxidative and uv stress is not known. this study of ccscc is limited in that ccscc is a rare subtype of scc. acquiring larger numbers of tumor takes time to accrue, therefore an observational retrospective study was used. in addition, our findings may be regionally dependent as other geographic zones may experience varying results depending on climate, environment, and cultural practices that can affect solar skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 137 exposures habits. also, limited history was available in those persons who had ccscc cases, since there was only access to the information present in the csp database. review of the literature and this study of ccscc do not indicate if the degree of clear cell change correlates with prognostic outcomes in comparison with other clear cell lesion subtypes, such as the odontogenic, salivary, oral squamous cell and metastatic variety; all of which are known to have a more aggressive biologic behavior.10,11 the literature on ccscc to date suggests that this subtype has an intermediate potential for metastasis when compared to other scc subtypes but more studies are needed to better understand ccscc behavior.2 in summary, this study validates past observations that ccscc occur more commonly in elderly individuals in areas of high photo-exposure such as the head and neck. this study identifies that men under the age of 70 are not only at greater risk of this type of scc but are also diagnosed on average 7 years earlier than females. in addition, our findings demonstrated that individuals who had ccscc likely had an additional non-clear cell skin cancer present in the same anatomic region. further research is still needed to better understand the nature and behavior of this rare cutaneous scc subtype. keywords: clear cell, squamous cell carcinoma, dermatopathology abbreviations: bcc: basal cell carcinoma ccscc: clear cell squamous cell carcinoma ccsccis: clear cell squamous cell carcinoma in situ csp: cleveland skin pathology hpv: human papilloma virus ors: outer root sheath pas: periodic acid–schiff scc: squamous cell carcinoma sccis: squamous cell carcinoma in situ uv: ultraviolet conflict of interest disclosures: none funding: none irb approval status: reviewed and approved by kansas city university of medicine and biosciences irb; approval #1321472-1 corresponding author: mathew loesch, do phd 1801 s. highland ave. suite l40 lombard, il 60148 email: mmloesch@gmail.com references: 1. lawal ao, adisa ao, olajide ma, olusanya aa. clear cell variant of squamous cell carcinoma of skin: a report of a case. j oral maxillofac pathol. 2013 jan;17(1):110-2 2. cassarino ds, derienzo dp, barr rj. cutaneous squamous cell carcinoma: a comprehensive clinicopathologic classification--part two. j cutan pathol. 2006 apr;33(4):261-79 3. requena l, sánchez m, requena i, alegre v, sánchez yus e. clear cell squamous cell carcinoma. a histologic, immunohistologic, and ultrastructural study. j dermatol surg oncol. 1991 aug;17(8):656-60. 4. al-arashi my, byers hr. cutaneous clear cell squamous cell carcinoma in situ: clinical, histological and immunohistochemical characterization. j cutan pathol. 2007;34:226–33. 5. kuo t. clear cell carcinoma of the skin. a variant of the squamous cell carcinoma that simulates sebaceous carcinoma. am j surg pathol. 1980;4:573–83. 6. misago n, toda s, narisawa y. tricholemmoma and clear cell squamous cell carcinoma (associated with bowen's disease): immunohistochemical profile in comparison to normal hair follicles. am j dermatopathol. 2012 jun;34(4):394-9. 7. dalton sr, leboit pe. squamous cell carcinoma with clear cells: how often is there evidence of trichilemmal differentiation? am j dermatopathol. 2008 aug:30(4):333-9. 8. corbalán-vélez r, ruiz-macia ja, brufau c, lópez-lozano jm, martínez-barba e, conclusion mailto:mmloesch@gmail.com skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 138 carapeto fj. clear cells in cutaneous squamous cell carcinoma. actas dermosifiliogr. 2009 may;100(4):307-16. 9. cohen pr, schulze ke, rady pl, tyring sk, he q, martinelli pt, nelson br. coincidental consort clear cell cutaneous carcinoma: facial squamous cell carcinoma in situ containing human papillomavirus and cancer cells with clear cytoplasm in an octogenarian couple. south med j. 2007 may;100(5):525-30. 10. kaliamoorthy s, sethuraman v, ramalingam sm, arunkumar s. a rare case of clear cell variant of oral squamous cell carcinoma. j nat sci biol med. 2015 jan-jun;6(1):245-7. 11. khoury zh, bugshan a, lubek je, papadimitriou jc, basile jr, younis rh. glycogen-rich clear cell squamous cell carcinoma originating in the oral cavity. head neck pathol. 2017 dec;11(4):552-560. skin january 2018 volume 2 issue 1 copyright 2018 the national society for cutaneous medicine 75 brief articles steatocystoma multiplex: case report and review of treatment mina amin bs a , peter hashim md mhs b a university of california, riverside, school of medicine, riverside, ca b department of dermatology, icahn school of medicine at mount sinai, new york, ny steatocystoma multiplex (sm) is a rare cutaneous disorder characterized by multiple asymptomatic skin-colored nodules. 1 although sm can involve any portion of the body, areas with a high number of sebaceous glands, including the neck, trunk, axilla, groin, scalp, and proximal extremities are commonly affected. 1,2 the inheritance pattern is considered to be autosomal dominant, although sporadic cases of sm have also been reported. the incidence of sm is evenly distributed across genders. 2 given that sm typically appears during adolescence, variations in hormone levels during puberty may trigger the development of the disease. 2 in a subtype of sm, referred to as steatocystoma multiplex suppurativa, cysts can become inflamed and subsequently rupture, leading to secondary infection and abscess formation. 1 keratin 17 is an intermediate filament found in the epithelial cells of the nail bed, hair follicle, and sebaceous gland. 3 pachyonychia congenita (specifically, pachyonychia congenita krt17, formerly known as pachyonychia congenita type 2) and sm have both been associated with a mutation in the gene encoding keratin 17. moreover, sm has been associated with eruptive vellus hair cysts and some authors consider these two entities to be on the same spectrum of pathologic disease processes. 4 abstract steatocystoma multiplex, an uncommon autosomal dominant disorder, is characterized by numerous asymptomatic skin-colored cystic nodules. the leading hypothesis regarding the pathophysiology of this disease involves a defect at the pilosebaceous duct junction, which leads to cyst formation. herein, we describe a case of a male patient that presented with steatocystoma multiplex. we examine the cosmetic outcomes of different techniques used in his treatment as well as review the varied therapeutic options available to such patients, including surgical removal, needle aspiration, cryotherapy, isotretinoin, and co2 laser treatment. introduction skin january 2018 volume 2 issue 1 copyright 2018 the national society for cutaneous medicine 76 a 26-year-old male presented with cysts involving multiple areas of the body since 12 years of age. the cysts first appeared on his chest, and then subsequently involved his neck, waist, and abdomen. no treatment was used in the past. a biopsy performed five years to his presentation revealed a diagnosis of steatocystoma multiplex. his past medical history was noncontributory. there was no family history of similar lesions. on examination of the skin, multiple, firm, mobile, skin-colored nodules varying from 0.5-3 cm in size were observed on the chest, neck, abdomen, and arms (figures 1 & 2). three of the cysts were chosen to each undergo a different treatment: simple incision and drainage (labeled a), incision and drainage followed by electrodessication (labeled b), and incision and drainage followed by the application of trichloroacetic acid (labeled c). the patient presented for follow-up at 2 weeks, and his healing wounds were evaluated for cosmetic outcomes (figure 3). figure 1. multiple soft cysts on the neck and chest. figure 2. numerous cysts are located on the lateral side of the chest. figure 2. cyst removal by incision and drainage was followed by (a) no further treatment, (b) electrodessication, or (c) tricholoroacetic acid treatment, respectively. at two week followup, all three lesions were healing well. case report skin january 2018 volume 2 issue 1 copyright 2018 the national society for cutaneous medicine 77 multiple different treatment options have been described for sm. cryotherapy has been associated with scarring, blistering, hyperpigmentation, hypopigmentation, and poor cosmetic outcomes. 1-2 however, a combination of cryotherapy to nonsuppurative lesions in a patient with sm suppurativa has also been reported with successful cosmetic results. 1 inflamed and suppurative lesions respond well to isotretinoin; however, non-inflamed cystic lesions remain unchanged after isotretinoin treatment. 5 the antiinflammatory effect of isotretinoin likely accounts for this finding. one exacerbation of sm with severe inflammation after isotretinoin use has also been reported. 6 nevertheless, patients with inflamed cystic lesions could potentially benefit from isotretinoin treatment. 5 the extent of involvement of the condition can make surgical removal of multiple lesions challenging. madan et al. used co2 laser to perforate the cyst wall. 7 a volkmann’s spoon was used to evacuate the cyst and the cyst healed by secondary intention and the cosmetic outcome was favorable. rossi et al. also utilized co2 laser to perforate the cyst wall of lesions on the face, with subsequent mechanical evacuation of the cyst contents or the cyst walls of small cysts were vaporized. 8 co2 laser therapy is a minimally invasive option for treating multiple lesions that provides favorable aesthetic outcomes and a low recurrence rate. 8 choudhary et al. described the use of a radiofrequency instrument to create tiny incisions into the cysts under local anesthesia. 9 subsequently, the content of the cysts were manually expressed with the thumb and the index finger. forceps were then used to grip the wall of the cyst and the sac of the cyst was extracted through small incisions. the lesions healed by secondary intention without any scar or postinflammatory hyperpigmentation. follow-up approximately 6 months later demonstrated favorable cosmetic outcome. lee et al. utilized a no. 11 blade to make a small incision in the cyst, a vein hook was then used to pull the cyst out, followed by the use of mosquito forceps to completely remove the contents of the cyst. 10 transient post-inflammatory hyperpigmentation was present but recurrence did not occur. oertel et al. reported the use of fine needle aspiration in three patients with no scarring. 11 egebert reported a severe case with extensive cysts in which hospitalization, oral antibiotics, incision and drainage, and electrocautery under general anesthesia. 12 according to the literature, this is the first report that directly compares the outcomes of three different treatments performed for a patient with sm. in our case, cyst removal by simple incision and drainage (a) and incision and drainage followed by electrodessication (b) both yielded the best cosmetic outcomes at two-week follow up (figure 3). the patient noted that the lesion treated with trichloroacetic acid application (c) after incision and drainage was associated with increased irritation relative to the other two lesions (figure 3). further follow-up will be needed to evaluate for possible recurrences using these different techniques. for the remaining lesions, multiple treatment options were discussed with the patient. incision and drainage of all of lesions was considered impractical due to the extent of discussion skin january 2018 volume 2 issue 1 copyright 2018 the national society for cutaneous medicine 78 involvement of his skin lesions and potential risk for scarring. as a result, the patient decided not to undergo surgical removal of his remaining lesions. instead, he intends to receive treatment for his remaining lesions with co2 laser therapy. despite the benign nature of sm, the quantity and extent of lesions can negatively impact the quality of life of these patients. multiple treatment options are available, but there lacks a consensus on optimal treatment. disease burden and patient preference remain important factors in pursuing therapeutic strategies. thus, a discussion with patients regarding the benefits and limitations of each therapeutic option available is essential before formulating a personalized treatment plan that is ultimately tailored to the individual patient. conflict of interest disclosures: none. funding: none. corresponding author: mina amin, bs university of california, riverside, school of medicine 900 university avenue riverside, ca, 92521 818-585-4873 minaamin06@gmail.com references: 1. apaydin r, bilen n, bayramgürler d, başdaş f, harova g, dökmeci ş. steatocystoma multiplex suppurativum: oral isotretinoin treatment combined with cryotherapy. australas j dermatol. 2000;41(2):98100. 2. alsabbagh mm. steatocystoma multiplex: a review. journal of dermatology & dermatologic surgery. 2016;20(2):91-9. 3. covello sp, smith fj, sillevis smitt jh, paller as, munro cs, jonkman mf, uitto j, mclean wh. keratin 17 mutations cause either steatocystoma multiplex or pachyonychia congenita type 2. br j dermatol. 1998;139(3):475-80. 4. ohtake n, kubota y, takayama o, shimada s, tamaki k. relationship between steatocystoma multiplex and eruptive vellus hair cysts. j am acad dermatol. 1992;26(5):876-8. 5. statham, b.n., cunliffe, w.j., 1984. the treatment of steatocystoma multiplex suppurativum with isotretinoin. br j dermatol. 3, 246. 6. rosen bl, brodkin rh. isotretinoin in the treatment of steatocystoma multiplex: a possible adverse reaction. cutis. 1986; 40: 115-20. 7. madan v, august pj. perforation and extirpation of steatocystoma multiplex. int j dermatol. 2009;48(3):329-30. 8. rossi r, cappugi p, battini m, mavilia l, campolmi p. co2 laser therapy in a case of steatocystoma multiplex with prominent nodules on the face and neck. int j dermatol. 2003;42(4):302-4. 9. choudhary s, koley s, salodkar a. a modified surgical technique for steatocystoma multiplex. j cutan aesthet sur. 2010;3(1):25. 10. lee sj, choe ys, park bc, lee wj, kim dw. the vein hook successfully used skin january 2018 volume 2 issue 1 copyright 2018 the national society for cutaneous medicine 79 for eradication of steatocystoma multiplex. dermatol surg. 2007;33(1):82-4. 11. oertel yc, scott dm. fine needle aspiration of three cases of steatocystoma multiplex. ann diagn pathol. 1998;2(5):318-20. 12. egbert bm, price nm, segal rj. steatocystoma multiplex report of a florid case and a review. arch dermatol. 1979;115(3):334–335. skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 621 original research a machine learning-based test for predicting response to psoriasis biologics jerry bagel, md1, yipeng wang, md, phd2, paul montgomery, iii2, christian abaya2, eric andrade2, courtney boyce2, tatiana tomich2, byung-in lee, phd2, david pariser, md3, alan menter, md4, tobin j. dickerson, phd2 1 the psoriasis treatment center of central new jersey, east windsor, nj 2 mindera health, san diego, ca 3 eastern virginia medical school and virginia clinical research, inc., norfolk, va 4 baylor university medical center, dallas, tx abstract objective: this study was designed to develop and prospectively validate a machine learning based algorithm that could predict patient response to the most common biologic drug classes used in the management of psoriasis patients. this type of tool would allow clinicians to have greater confidence that a given patient will respond to a specific drug class, which could lead to improved health outcomes and reduced wasted healthcare spend. methods: patients were enrolled into one of two observational studies (stamp studies) where dermal biomarker patches (dbps) were applied at baseline prior to drug exposure, followed by clinical evaluations at 12 weeks after exposure. pasi measurements were made at baseline and 12 weeks to evaluate clinical response to a clinical phenotype. responders were defined as those who reached pasi75 at 12 weeks. the transcriptomes obtained from the dbps were sequenced and analyzed to derive and/or validate classifiers for each biologic class, which were then combined to yield predictive responses for all three biologic drug classes (il-23i, il-17i, and tnfi). results: a total of 242 psoriasis patients were enrolled in these studies, including 118 patients (49.6%) treated with il-23i, 79 patients (33.2%) treated with il-17i, 35 patients (14.7%) treated with tnfi, and 6 patients (2.5%) treated with il-12/23i. the il-23i predictive classifier was developed from the earlier enrolled patients and independently validated with the latter enrolled patients. il -17i and tnfi predictive classifiers were developed using publicly available datasets and independently validated with patients from the stamp studies. in the independent validation, positive predictive values for three classifiers (il-23i, il-17i, and tnfi) were 93.1%, 92.3% and 85.7% respectively. over the entire cohort, 99.5% of patients were predicted to respond to at least one drug class. conclusion: this study demonstrates the power of using baseline dermal biomarkers and machine learning methods as applied to the prediction of patient response to psoriasis biologics prior to drug exposure. using this test, patients, physicians, and the health care system all can benefit in distinct ways. precision medicine can be realized for individual patients as most will likely respond to their prescribed biologic the first time. physicians can prescribe these drugs with increased confidence, and the healthcare system will realize lower net costs as well as greatly reduced wasted spend by significantly improving initial response rates to expensive biologic therapeutics. skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 622 the promise of personalized medicine has been touted for many years but has been elusive in some specialties.1 recently, with the influx of large data sets from “omics”based methods including genomics, transcriptomics, and metabolomics, personalized approaches to medical practice have come to the forefront and many specialties now use some form of personalized medicine in research and clinical care. this is particularly true in oncology where biomarker-guided treatment paradigms are increasingly commonplace.2 however, personalized medicine in dermatology has traditionally lagged behind other medical specialties. advances in the molecular understanding of the skin as well as advances in cutaneous pathophysiology have initiated new lines of thinking for the application of personalized medicine to the treatment of the skin. these successes were first realized in melanoma and current treatment guidelines for metastatic melanoma recommend testing tissue for relevant mutations (nrs, braf, kit, gnaq/11, and/or bap1) with the goal of treatment that is personalized for a specific patient.3 however, other inflammatory skin diseases continue to have a need for personalized approaches. indeed, the american academy of dermatology (aad) and national psoriasis foundation (npf) joint guidelines on the treatment of psoriasis with biologic agents stated the urgent need for the identification of biomarkers that can guide efficient biologic selection for individual patients was highlighted.4 psoriasis is a t-cell mediated inflammatory skin disease characterized by discrete erythematous plaques and papules with micaceous scale.5 worldwide, this is a common disease, with approximately 2.8% of the united states population, or 7.5 million people, diagnosed with psoriasis. the pathology of the disease has been heavily studied and is known to be triggered by a complex inflammatory circuit that stimulates keratinocyte proliferation via upregulation of a host of cytokines including tumor necrosis factor-alpha (tnf), interleukin (il)-17, and il-23.6 current treatment paradigms for psoriasis are distinguished by topical medications and/or phototherapy for mild to moderate patients, and systemic medications for patients who are classified as moderate to severe disease. the advent of biologic therapy as one of these systemic agents has revolutionized the management and treatment of psoriasis patients and is a direct result of the increased molecular understanding of the disease.7 presently, there are eleven approved biologic agents approved for use in the united states for the treatment of psoriasis, with more under development. these monoclonal antibodies are highly specific immunomodulators and have proven to be particularly effective and safe in the clearance of skin lesions. this increase in treatment options has come with a concomitant increase in patient expectations for disease control.8 even with the plethora of treatment options available today, the most common reason patients discontinue biologic treatments is lack of efficacy.9 indeed, recently published real world evidence reported response rates to biologics that are significantly lower than those observed in clinical trials.10 while broad stroke patient stratification measures have been reported, their value is limited in clinical practice. biologic drugs, while effective, are also particularly expensive; the cost of medication necessary to reach skin clearance (pasi 100) can cost up to $366,645 per patient annually.11 when one introduction skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 623 considers the combination of a lack of clarity to which biologic is most effective for a given patient along with the significant cost for biologics, the need for biomarkers that predict treatment efficacy has never been greater. we recently described a novel biomarker capture platform that utilizes a proprietary dermal biomarker patch to capture the whole transcriptome including mrna biomarkers from the epidermis and upper dermis.12 this platform showed excellent concordance with biopsy and provides a scalable method to access skin biomarkers in a minimally invasive manner. furthermore, we have reported the use of this platform in preliminary machine learning classifier builds for the prediction of response and nonresponse to il-17 and il-23 inhibitors. herein, we extend this preliminary study to the development and prospective validation of an actionable clinical test for predicting patient response to psoriasis biologics for all three drug classes. dermal biomarker patch platform dermal biomarker patches (dbps) used in this study were fabricated and modified as previously described and used according to the manufacturer’s specifications.12 human subject recruitment and enrollment data were analyzed from past and ongoing observational, multicenter (20 centers), single‐arm, open‐label, 12-week studies, referred as stamp studies. the protocols for these studies were approved by local institution ethics committees and conforms to the provisions of the declaration of helsinki and the international council for harmonisation (ich) guidelines on good clinical practice (gcp). all patients who received treatment provided written informed consent. the primary objective of the study protocols was to examine if baseline or ontherapy transcriptomics can be used to help predict selection of medications and provide new therapeutic targets for drug development (supplemental table 1). visits included screening, baseline, week 1, week 4, week 8, and week 12. pasi, pga, and bsa scoring was performed at every visit excluding the screening visit. subjects were administered the dermal biomarker patch at every visit excluding the screening visit. subject medical history, physical exam, and demographics were collected at screening. study population these studies enrolled both male and female patients who were aged 18 years or older, diagnosed with psoriasis by either a rheumatologist or a dermatologist with at least one identifiable study lesion of 2 cm in diameter or greater, and were planned for treatment with il-23 inhibitor (il-23i), il-17 inhibitor (il-17i), or tnfα inhibitor (tnfαi) therapy once enrolled in the study. the exclusion criteria included use of topical steroids on the study lesion within 2 weeks prior to the baseline visit and concurrent use of plaquenil. all study participants were also instructed to refrain from the use of all topical steroids throughout the study until the end of study treatment. dermal biomarker patch application to apply dbps to the skin, a customized spring-loaded applicator was used. this applicator served to standardize the application pressure across subjects and users. the loaded applicator was placed against the skin and the trigger pressed, applying the patch to the skin. the patch was methods skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 624 then held in place against the skin for 5 minutes by a ring of medical tape. after this time, the patch was removed from the subject, immediately placed into storage buffer (licl, triton x-100, tris-edta), and stored at 4 ˚c until processing. dermal biomarker patch processing dermal transcriptomes were processed within 96 hours of collection from subjects. the applied dbps were washed with chilled 1x pbs and then dried under a stream of nitrogen. mrna extraction from the patch was performed by applying pcr grade water (50 µl, 95 ˚c) to the dbp. the patch was then heated 1 minute at 95 ˚c to elute the bound mrna from the dbp. this eluted mrna was then converted to cdna using the takara smart-seq® single cell kit according to the manufacturer’s instructions. amplified cdna samples were then stored at -20˚c until analysis. next-generation sequencing procedures amplified cdna was sequenced by a commercial vendor (psomagen, inc., rockville, md) according to standard procedures. library preparation was accomplished using illumina nextera dna flex kits according to the manufacturer’s instructions. prepared indexed libraries were then loaded onto a novaseq6000 s4 with read length of 150pe for sequencing of 40 m reads per sample. during sequencing, the quality score (q30) was maintained over 75%. upon completion of sequencing runs, fastq file quality was checked with fastqc and trimmed with the trim_galore program. the trimmed fastq files were aligned and mapped to human reference genome grch38 using the hisat2 program. the number of reads was counted for each ensemble gene id using the featurecounts program and homo sapiens grch38.84.gtf. rna expression analysis was further processed using the bioconductor package edger. genes were filtered using filterbyexpr before logcpm (log counts per million reads) were calculated as a measure of gene expression level. for downstream classifier builds, logcpm values were used. il-23 classifier development five common classifiers were selected and applied for predicting responders under il23i treatment using the r package caret. the selected classifiers have been frequently used in the medical field for exploring predictive or prognostic biomarkers and included glmnet (lasso and elastic-net regularized generalized linear model), pam (nearest shrunken centroids), lm (linear regression model), svm (support vector machine), and rf (random forest). the five classifiers were compared for their predictive performance using the following experimental design: 1) the data set was split into ten stratified outer folds; 2) for each of the folds, the data were preprocessed for feature selection. the top 20, 50, or 200 differentially expressed genes (features) were selected using linear regression model; 3) the hyperparameters were tuned in the training set via a ten-fold cross-validation, and the process subsequently repeated five times; 4) based on the selected hyperparameters, a model was derived from the training set and applied to the test set. performance metrics on the test set were then calculated. this process was repeated five times for each classifier. the earliest enrolled il-23i treated patients in stamp studies were used for il-23i classifier training. baseline pasi filter (none, 6+, 8+, and 10+) were applied to explore the impact of disease severity on classifier performance. classifier training were performed using the machine learning approaches stated above and test performance was assessed using skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 625 10-fold cross validation. il-23i classifier were locked once a desired performance (> 85% ppv and >85% sensitivity) were achieved. the il-23i treatment patients enrolled after the classifier lock were used as the independent validation set. il-17 classifier development previously we have reported a list of 17 genes which were predictive of psoriasis patients’ response to il-17i by analyzing a publicly available data set.13,14 in brief, moderate to severe psoriasis patients (baseline pasi ≥ 10) were treated with brodalumab and the patients were followed up for 12 weeks. pasi measurement were performed at baseline and week 12, and patients’ treatment response was assessed using week 12 pasi75. lesional and nonlesional skin biopsy samples were collected at baseline and week 12. rna profiling was performed using an affymetrix microarray platform. the lesional samples collected at baseline were used in our predictive biomarker analysis. the 17 predictive genes were negatively correlating with patients’ response to brodalumab. the 17 genes were mapped to 14 ensemble gene ids reported in rnaseq data from stamp studies. the 14-gene classifier was validated in stamp studies. tnfi classifier development publicly available data sets in the ncbi gene expression omnibus (geo) database (https://www.ncbi.nlm.nih.gov/geo/) and european bioinformatics institute (emblebi) big data database (https://www.ebi.ac.uk/) were used as the classifier training data sets. for initial data selection, search terms of psoriasis patients with biologics treatment and transcriptome profiles were used to identify either array or sequencing data. supervised predictive biomarker selection was applied to individual training data to filter genes based on the following assessment: 1) correlation between gene expression and patient response; 2) median gene expression level; 3) gene expression dynamic range; 4) difference between average gene expression of responder and non-responders. ratios of genes down-regulated and gene upregulated in tnfi responders were used to develop a prediction of tnfi treatment responses. prospective classifier validation il-23i, il-17i and tnfi classifiers were independently validated using the patients enrolled in stamp studies. each classifier discretely predicted a patient as either a responder or non-responder for biologic class. response was defined as achieving pasi75 at week 12. the cross-tabulation of observed and predicted classes with associated statistics was calculated with the confusionmatrix function of the r caret package. characteristics of study subjects a total of 242 psoriasis patients were enrolled in the stamp studies (figure 1) at time of data lock, including 38 patients who were still in follow up. stamp is an actively recruiting study designed to continue enrolling new patients to support psoriasis biomarker research. varied demographics and clinical features of the study subjects were observed (table 1). with regard to drug class, 49.6% patients were treated with il-23i, 33.2% were treated with il-17i, 14.7% were treated with tnfi, and 2.5% were treated with il-12/23i. results skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 626 of the 242 patients initially identified for this study, 185 patients completed the study, meaning that both baseline and week 12 pasi scores were collected, and 57 patients were either screen failures, lost to follow up, or still in follow up. out of the 185 patients, 177 had baseline dbp samples collected, while 8 patients failed dbp sample collection. of this subset, 167 samples passed sequencing data qc metrics and were included in the biomarker analysis, with 10 (5.4%, 10/177) samples failing either sample processing or sequencing data qc. the patient response rate was 64.1% for the whole cohort, and ranged from 47.6% to 72.5% for different biologics (supplemental table 2). high (baseline pasi ≥ 8) pasi patients had 26.4% higher response rate than low pasi patients across all drug classes. high (baseline pasi ≥ 8) pasi patients were used for predictive classifier development and validation. the il-23i treated patient population was divided into two subsets, 17 il-23i treated patients were used for training an il-23i predictive classifier, and the remaining 43 patients were used for prospective validation. all high pasi il-17i and tnfαi patients were used for the classifier validation. il-23i classifier development and performance in training set a subset of 17 il-23i treated high pasi (≥8) patients were used for il-23i predictive classifier training, including 9 responders and 8 non-responders. the best performing model was built on glmnet using the top 50 features selected with linear regression model. test performance was assessed with ten-fold cross validation and the positive predictive value (ppv), sensitivity and balanced accuracy were 89.7%, 96.3%, and 91.9%, respectively. tnfi data source and predictive biomarker discovery four publicly available datasets (table 2) were identified and used for the tnfi response classifier development.15,16,17,18 a total of 73 patients were included in these datasets, out of which 58 patients had both transcriptome data and outcome assessment data for predictive biomarker discovery. patient outcome was assessed with pasi75 at week 12 or 16, or histological response. supervised predictive biomarkers selection was applied to the four training data sets. nine genes were determined as predictive of tnfi response in at least two datasets (cnfn, ctsc, gbap1, crabp2, pcdh7, ppig, rab31, c3, egr1). interestingly, cnfn was previously reported as a key gene determining psoriasis molecular classes and egr1 was well known as key regulator in the psoriatic transcriptome.19,20 the output of the classifier was a tnfi response prediction score; in this scoring system, the lower the prediction score, the higher chance the patient will respond to tnfi treatment. the classifier performance showed ppv, sensitivity and balanced accuracy of 78.9%, 44.1%, and 63.7%, respectively with this training set (supplemental table 3). mind.px classifier validation patient demographics and disease characteristics for the 95 patients included in the prospective validation can be found in supplemental table 4. only patients with baseline pasi≥8 were included in the validation. for the three classifiers, positive predictive value ranged from 85.7% to 93.1% (table 3). correlation between observed w12 pasi changes and predicted drug response were assessed (figure 2). the same analysis was repeated for 66 moderate to severe disease patients (i.e., skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 627 pasi≥10), and similar overall test performance was observed with ppv ranging from 90% to 100% in this smaller cohort (supplemental table 5). patients with baseline pasi<8 were also analyzed to determine the classifier performance in milder patients. in this case, the balanced accuracy ranged from 44.4% to 52.8% for three classifiers, suggesting that the developed classifier was optimized for moderate to severe psoriasis patients. mind.px predicted response prevalence the predicted response prevalence of patients by all three classifiers (il-23i, il-17i and tnfi) was assessed using 195 patients who had baseline dbp samples and completed rnaseq sequencing data (figure 3 and table 4). individually, the predicted response prevalence was 72.3%, 51.7% and 67.1% for il-23i, il-17i and tnfi classifiers, respectively. critically, 99.5% (194/195) patients were predicted as to responder to at least one of the three drug classes. all possible combinations of the three drug classes were represented with 17.4% (34/195) of patients predicted as a responder to all three drug classes, 56.9% (111/195) of patients predicted as a responder to two of the three drug classes, and 25.1% (49/195) of patients predicted as a responder to one of the three drug classes. stamp study demographics there were 242 patients included in this analysis, with demographics that largely were consistent with previous studies with respect to gender, race, and age (table 2). similarly, the average patient in these studies was obese (bmi>30), with a mean age of 48.5 years. most interestingly, in this study, the vast majority of patients (86%) were biologic naïve or had not been administered a biologic within the past 12 weeks. given that many moderate to severe psoriasis patients have been exposed to biologics, this finding was particularly surprising, but analysis of the classifier response of biologic naïve versus biologic exposed patients showed no difference between the predictive value of the algorithms in either of these patient groups (data not shown). classifier development and validation the final il-23i classifier was developed and validated using patients enrolled in the stamp studies. a subset of the total il-23i enrolled patients were used as the training set and the remaining patients in the cohort were used for classifier validation. since the training and test set were from the same study with the sample and data processed in the same manner, the classifier developed with the training set can be applied to the discussion skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 628 figure 1. stamp study patient sample enrollment and analysis flow chart skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 629 figure 2. correlation between predicted response and patient week 12 pasi changes in psoriasis patients from independent validation data set. left. 43 patients treated with il-23i; middle. 31 patients treated with il-17i; right. 11 patients treated with tnfi. x-axis: predicted responder or non-responder; y-axis: week 12 pasi changes. red dot: median pasi change value figure 3. mind.px predicted response prevalence in patients enrolled in the stamp studies skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 630 test set without the need for additional normalization. the strategy for the development of the il-17i and tnfi classifiers was different from the il-23i classifier. the il-17i and tnfi patient sample sizes in stamp studies were smaller than il-23i patients and were not sufficient to divide into separate training and test sets, so publicly available datasets were used for the training of these two classifiers. it was noted that the training sets from the public data differed significantly than the test sets in some aspects, including sample collection method (punch biopsy vs. dermal patch), rna preparation protocol, transcriptome profiling method (array vs. sequencing based). due to these different natures of the training sets, the training sets primarily were used only for feature selection. once the predictive genes were identified, a simplified algorithm that utilized gene expression values or the ratio of gene expression values, was applied as the predictive classifier. the cutoffs were preset prior to the validation using percentile data values calculated from the prediction scores of stamp patients and this allowed for an assessment of classifier performance while minimizing the risk of overfitting. here, week 12 pasi75 was used as the patient outcome determination. in a clinical setting where a better response (e.g., pasi 90 or pasi 100) is desired, our classifier can potentially be used for the identification of this group of patients with certain clinical cutoff adjustment. further classifier development to conclusively identify “super-responders” or “super-non-responders” is ongoing and will be reported in due course. all three classifiers were validated for baseline pasi ≥ 8 patients. however, the predictive value of these classifiers in patients with lower starting pasi scores was limited. this could be because the three classifiers were developed with high (≥ 10) pasi patients as the training set in order to match the types of patients that were enrolled in the pivotal clinical studies for each biologic. it is possible that a mild patient might biologically have different transcriptomic biomarkers. alternatively, in patients with low starting pasi scores, the reliability of the response determination measure (pasi 75) is low given the reduced dynamic range of the measurement. other clinical variables have been previously used to stratify psoriasis patients or have been correlated with poorer outcomes. in particular, bmi and age have been reported as having clinical prognostic value in assessing biologic treatment response.21,22,23 we have explored the predictive significance of bmi and age as a possible orthogonal input variable in the classifier. however, adding either variable as a covariate when exploring the predictive models, no improvement was observed in the predictive accuracy or positive predictive value (data not shown). the prevalence of the biomarker predicted response revealed key features of this test. of those tested, only a single patient out of the 195 patients tested was predicted to not respond to any of the three biologic drug classes. given the rarity of the “triple negative” outcome, the biological rationale for this patient’s failure is impossible to determine without a larger data set. it is possible that patients that fail all three classes of biologics have an altered immune system; greater study of these patients is required to fully elucidate the mechanism underpinning this phenotype. these data concur with a widely accepted clinical fact that the treatment and management of psoriasis has dramatically changed since the introduction of biologics; almost all patients will respond to one of the three skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 631 table 1. stamp study patient demographics and disease characteristics patient population (n=242) sex 242 male 112 (46.3%) female 130 (53.7%) race 241 white 193 (80.1%) asian 19 (7.9%) black or african american 16 (6.6%) others 13 (5.4%) age 241 48.5 ± 13.7 body mass index 238 31.9 ± 7.0 pasi 238 11.1 ± 9.1 biologics class 238 il-23 inhibitor 118 (49.6%) il-17 inhibitor 79 (33.2%) tnf inhibitor 35 (14.7%) il-12/23 inhibitor 6 (2.5%) psoriasis subtypes 239 plaque psoriasis 226 (94.6%) psoriatic arthritis 9 (3.8%) others 4 (1.6%) prior biologics history 214 biologics naive 134 (62.6%) treated with biologics within past 12 weeks 50 (23.4%) treated with biologics over 12 weeks ago 30 (14.0%) values are n (%) of patients or mean ± standard deviation skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 632 table 2. publicly available datasets for tnfi classifier training id dataset accession # year published treatment pt response criteria sample size transcriptome profiling platform #1 gse8503415 2017 adalimumab pasi75 at wk 16 14 illumina humanht12 v4.0 expression beadchip #2 gse1190316 2009 etanercept histological response (epidermal thickness) at wk 12 15 affymetrix hgu133a_2 #3 gse11723917 2019 etanercept pasi75 at wk 12 34 affymetrix hgu133_plus_2 #4 e-mtab-655618 2019 etanercept pasi75 at wk 12 10 rnaseq table 3. classifier validation test performance of three classifiers on patients with baseline pasi≥8 classifier sample size number of responder number of nonresponder ppv npv sensitivity specificity balanced accuracy il-23i classifier 43 37 6 93.1% 28.6% 73.0% 66.7% 69.8% il-17i classifier 31 26 5 92.3% 22.2% 46.2% 80.0% 63.1% tnfi classifier 11 7 4 85.7% 75.0% 85.7% 75.0% 80.4% skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 633 table 4. mind.px predicted response prevalence in patients enrolled in the stamp studies classes of biologics. however, a disconnect was observed between biologic prescribing behavior and the predicted biologic class from the test. while only 14.7% of the enrollees in the observational stamp study were prescribed tnfi biologics (49.6% of the patient cohort), 67% of the patient population was predicted to respond to this class. by combining our previously reported dermal biomarker patch platform with machine learning methods, we have developed an actionable machine learning-based precision medicine test that can predict psoriasis patient response to biologics (tnfi, il17i, or il23i) with high positive predictive value. interestingly, when the entire patient cohort was examined, almost all patients were predicted to respond to at least one biologic class, highlighting the tremendous efficacy of biologic drugs in treating psoriasis. using baseline biomarkers combined with machine learning algorithm development, the proper biologic for a given patient can be prescribed the first time. this test could lead to improved patient outcomes while also translating into tremendous cost savings for healthcare systems. we envision that this test can effectively minimize the trial-and-error approach to the biologic treatment of psoriasis, and provide physicians, patients, and payers with a powerful tool to bring personalized medicine to the management of psoriasis patients. conflict of interest disclosures: j. bagel has received research funds payable to psoriasis treatment center and/or speaking/consultant fees from abbvie, amgen, arcutis biotherapeutics, boehringer ingelheim, bristol myers squibb, celgene corporation, corrona llc, dermavant sciences, ltd, dermira/ucb, eli lilly, glenmark pharmaceuticals ltd, janssen biotech, kadmon corporation, leo pharma, lycera corp, menlo therapeutics, mindera health, novartis, pfizer, regeneron pharmaceuticals, sun pharma, taro pharmaceutical industries ltd, ucb, and valeant pharmaceuticals. p. montgomery, c. abaya, e. andrade, c. boyce, and t. tomich are employees of mindera health. y. wang, b.-i. lee, and t. dickerson are employees and shareholders of mindera health. d. pariser is a consultant (honoraria) for atacama therapeutics, bickel biotechnology, biofrontera ag, bristol-myers-squibb, celgene, dermira, leo pharma, mindera health, novartis, pfizer, regeneron, sanofi, theravida, and valeant. dr. pariser has also received research funding from almirall, amgen, aobiome, asana biosciences, bickel biotechnology, celgene, dermavant sciences, dermira, eli lilly, leo pharma, menlo therapeutics, merck, novartis, novo nordisk, ortho dermatologics, pfizer, and regeneron. a menter is a consultant (honoraria) for abbott labs, amgen, boehringer ingelheim, eli lilly, janssen biotech, leo pharma, mindera health, novartis, sunpharma, and ucb, inc. dr. menter has also received grant funding from abbott labs, amgen, boehringer ingelheim, celgene, janssen biotech, leo pharma, merck, and sunpharma. funding: this study was funded by mindera health. corresponding author: tobin j. dickerson, ph.d. mindera health 5795 kearny villa road san diego, ca 92123 phone: (858) 344-9290 email: tobin.dickerson@minderahealth.com class number of patients patient percentage non-respond to all drug classes 1 0.5% respond to all drug classes 34 17.4% respond to il17i & il23i 54 27.7% respond to il17i & tnfαi 10 5.1% respond to il23i & tnfαi 47 24.1% respond to il23i only 6 3.1% respond to il17i only 3 1.5% respond to tnfαi only 40 20.5% conclusion skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 634 references: 1. hamburg ma, collins fs. the path to personalized medicine. n engl j med. 2010; 363:301-304. doi: 10.1056/nejmp1006304 2. schilsky rl. personalized medicine in oncology: the future is now. nat rev drug discov. 2010;9(5):363-366. doi: 10.1038/nrd3181 3. webster rm, mentzer se. the malignant melanoma landscape. nat rev drug discov. 2014;13(7):491-492. doi:10.1038/nrd4326 4. menter a, strober be, kaplan dh, et al. joint aad-npf guidelines of care for the management and treatment of psoriasis with biologicsd. j am acad dermatol. 2019;80:1029-1072. doi:10.1016/j.jaad.2018.11.057 5. raju ss. psoriasis and lasting implications. expert rev clin immunol. 2014;10(2):175-177. doi:10.1586/1744666x.2014.872033 6. nograles ke, davidovici b, krueger jg. new insights in the immunologic basis of psoriasis. semin cutan med surg. 2010;29(1):3-9. doi:10.1016/j.sder.2010.03.001 7. kamata m, tada y. safety of biologics in psoriasis. j dermatol. 2018;45(3):279-286. doi:10.1111/1346-8138.14096 8. strober, be, van der walt jm, armstrong aw, et al. clinical goals and barriers to effective psoriasis care. dermatol ther (heidelb) 2019;9:518. doi: 10.1007/s13555-018-0279-5 9. menter a, papp ka, gooderham m, et al. drug survival of biologic therapy in a large, diseasebased registry of patients with psoriasis: results from the psoriasis longitudinal assessment and registry (psolar). j eur acad dermatol venereol jeadv. 2016;30(7):1148-1158. doi:10.1111/jdv.13611 10. enos cw, o'connell ka, harrison rw, et al. psoriasis severity, comorbidities, and treatment response differ among geographic regions in the united states. jid innovations. 2021;1(2):100025. doi:10.1016/j.xjidi.2021.100025 11. wu jj, feldman s, rastogi s, et al. comparison of the cost-effectiveness of biologic drugs used for moderate-to-severe psoriasis treatment in the united states. j dermatolog treat. 2018;29(8):769-774. doi: 10.1080/09546634.2018.1466022 12. ibrahim sf, taft bj, wang y, et al. minimally invasive skin transcriptome extraction using a dermal biomarker patch. submitted. 13. tomalin le, russell cb, garcet s, et al. shortterm transcriptional response to il-17 receptor-a antagonism in the treatment of psoriasis. j allergy clin immunol. 2020;145(3):922-932. doi:10.1016/j.jaci.2019.10.041 14. wang y, lee b-i, montgomery iii, p, et al. efficient prediction of response to psoriasis biologics using a machine learning classifier. submitted. 15. correa da rosa, j, kim j, tian s, et al. shrinking the psoriasis assessment gap: early geneexpression profiling accurately predicts response to long-term treatment. j invest dermatol. 2017;137(2):305-312. doi:10.1016/j.jid.2016.09.015 16. zaba lc, suarez-farinas m, fuentes-duculan j, et al. effective treatment of psoriasis with etanercept is linked to suppression of il-17 signaling, not immediate response tnf genes. j allergy clin immunol. 2009; 124(5):1022–10.e1395. doi:10.1016/j.jaci.2009.08.046 17. brodmerkel c, li k, garcet s, et al. modulation of inflammatory gene transcripts in psoriasis vulgaris: differences between ustekinumab and etanercept. j allergy clin immunol. 2019;143(5):1965-1969. doi:10.1016/j.jaci.2019.01.017 18. foulkes ac, watson ds, carr df, et al. a framework for multi-omic prediction of treatment response to biologic therapy for psoriasis. j invest dermatol. 2019;139(1):100-107. doi:10.1016/j.jid.2018.04.041 19. ainali c, valeyev n, perera g, et al. transcriptome classification reveals molecular subtypes in psoriasis. bmc genomics. 2012;13:472. doi:10.1186/1471-2164-13-472 20. jeong sh, kim hj, jang y, et al. egr-1 is a key regulator of il-17a-induced psoriasin upregulation in psoriasis. exp dermatol. 2014;23(12):890-5. doi:10.1111/exd.12554 21. van voorhees as, mason ma, harrold lr, et al. characterization of insufficient responders to anti-tumor necrosis factor therapies in patients with moderate to severe psoriasis: real-world data from the us corrona psoriasis registry. j dermatolog treat. 2021;32(3):302-309. doi: 10.1080/09546634.2019.1656797 22. lockshin b, cronin a, harrison rw, et al. drug survival of ixekizumab, tnf inhibitors, and other il-17 inhibitors in real-world patients with psoriasis: the corrona psoriasis registry. dermatol ther. 2021;34(2):e14808. doi:10.1111/dth.14808 23. bewley a, hamptom pj, hughes j, et al. secukinumab treatment results in sustained improvement in apasi and drug survival: 24month follow-up from the british association of dermatologists biologics and immunomodulators register (badbir). aad 2020. p18239 skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 635 supplemental tables supplemental table 1. schedule of activities for stamp studies abbreviations: bmi = body mass index; ip = investigational product; pasi = psoriasis area and severity index; pga = physician global assessment; bsa = body surface area. 1 medical history includes prescription and over-the-counter medication history. 2 only applicable to subjects who have not been examined by a rheumatologist or dermatologist within 30 days prior to screening. height, weight, and bmi are included. 3 if screening and baseline occur on the same day, clinician must ensure subject has refrained from any topical steroid use 2 weeks prior to the application of the mindera dermal biomarker patch. 4 for screening/baseline assessments, the physical exam, pasi, pga, bsa, and/or mindera dermal biomarker patch application can be completed at either the screening visit or the baseline visit (pasi, pga, and bsa should be completed at the same visit and before mindera dermal biomarker patch application). visit number visit 1 visit 2 visit 3 visit 4 visit 5 visit 6 study week screening3 baseline3 week 1 week 4 week 8 week 12 informed consent x inclusion/exclusion criteria x demographics x medical history1 x physical exam2,4 x pasi4 x x x x pga4 x x x x bsa4 x x x x mindera dermal biomarker patch application4 x x x x x x adverse events x x x x x x ip accountability x x x x x skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 636 supplemental table 2. psoriasis patient response rates biologics no pasi filter pasi ≥ 8 pasi < 8 all biologics 64.1% (118/184) 74.3% (84/113) 47.9% (34/71) il-23i 64.2% (68/106) 70.8% (46/65) 53.7% (22/41) il-17i 72.5% (37/51) 84.8% (28/33) 50.0% (9/18) tnfαi 47.6% (10/21) 63.6% (7/11) 30.0% (3/10) supplemental table 3. test performance of tnfαi classifier on the training set sample size 58 number of responder 34 number of non-responder 24 ppv 78.9% npv 51.3% sensitivity 44.1% specificity 83.3% balanced accuracy 63.7% skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 637 supplemental table 4. classifier validation set patient demographics and disease characteristics il-23i classifier (n=43) il-17i classifier (n=31) tnfαi classifier (n=11) sex male 23 (53.5%) 21 (67.7%) 4 (36.4%) female 20 (46.5%) 10 (32.3%) 7 (63.6%) race white 35 (81.4%) 23 (74.2%) 9 (81.8%) others 8 (18.6%) 8 (25.8%) 2 (18.2%) age 48.3 ± 16.9 48.9 ± 12.9 47.8 ± 13.4 body mass index 31.1 ± 7.5 32.1 ± 6.3 32.6 ± 5.2 pasi 15.9 ± 8.5 17.5 ± 12.6 14.8 ± 5.4 psoriasis subtypes plaque psoriasis 41 (97.6%) 31 (96.8%) 11 (100%) others 1 (2.4%) 1 (3.2%) 0 (0%) values are n (%) of patients or mean ± standard deviation skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 638 supplemental table 5. classifier validation test performance of three classifiers on patients with baseline pasi≥10 classifier sample size number of responder number of nonresponder ppv npv sensitivity specificity balanced accuracy il-23i classifier 35 30 5 95.7% 33.3% 73.3% 80.0% 76.7% il-17i classifier 22 17 5 90.0% 33.3% 52.9% 80.0% 66.5% tnfi classifier 9 7 2 100.0% 66.7% 85.7% 100.0% 92.9% poster presented at the 36th fall clinical dermatology conference | las vegas, nv | october 12-15, 2017 confirmatory psychometric evaluation of the axillary sweating daily diary: a validated patient-reported outcome measure to assess axillary hyperhidrosis sweating severity dee anna glaser,1 adelaide a. hebert,2 sheri fehnel,3 dana dibenedetti,3 lauren nelson,3 janice drew,4 david m. pariser5 1saint louis university, st. louis, mo; 2uthealth mcgovern medical school at houston, houston, tx; 3rti health solutions, research triangle park, nc; 4dermira, inc., menlo park, ca; 5eastern virginia medical school and virginia clinical research, inc., norfolk, va introduction • hyperhidrosis affects an estimated 4.8% of the us population1; approximately three-quarters of patients experience negative psychological effects, with anxiety and depression occurring over 3.5-times more frequently in people with hyperhidrosis than in people without it1,2 • despite high prevalence and burden of disease, few disease-specific outcome measures are available – the hyperhidrosis disease severity scale (hdss) is widely used in clinical studies and well understood in clinical practice; however, it does not conform to current regulatory standards for patient-reported outcome (pro) measures used to support product approvals and labeling • the 4-item axillary sweating daily diary (asdd; table 1) and a child-specific 2-item version (asdd-c for use in patients ≥9 to <16 years of age; table 1) were developed according to current regulatory standards3 – the asdd/asdd-c axillary sweating severity item (item 2) was specifically developed for use as an endpoint in clinical trials in support of approval and labeling (and also as a useful clinical parameter) • in addition to the asdd, patients ≥16 years of age were asked to complete 6 weekly impact items designed to assess the impact and bother of hyperhidrosis on daily activities and a single-item patient global impression of change (pgic) to assess overall change in sweating severity (table 1) • initial psychometric evaluation of the asdd was conducted using data from a phase 2 study of topical glycopyrronium tosylate (gt; formerly drm04), an investigational treatment for primary axillary hyperhidrosis in patients ≥9 years of age; results have been previously reported and provide preliminary support for the use of this measure to evaluate the efficacy of axillary hyperhidrosis treatment in clinical trials4 objective • to confirm and extend the psychometric evidence supporting asdd/asdd-c axillary sweating severity item (item 2) based on pooled data from two phase 3 clinical trials of gt: atmos-1 (drm04-hh04; nct02530281) and atmos-2 (drm04-hh05; nct02530294) methods study design • atmos-1 and atmos-2 were phase 3, multicenter (atmos-1: sites in us and germany; atmos-2: sites in us), parallel-group, 4-week, double-blind clinical trials in which patients with primary axillary hyperhidrosis were randomized (2:1) to gt or vehicle • eligible patients were ≥9 years of age (patients <16 years were only recruited at us sites) and had primary axillary hyperhidrosis for ≥6 months, with gravimetrically-measured sweat production of ≥50 mg/5 min in each axilla, asdd/asdd-c axillary sweating severity item (item 2) score ≥4, and hyperhidrosis disease severity scale (hdss) grade 3 or 4 assessments • axillary hyperhidrosis patient measures (ahpm) – asdd/asdd-c item 2 responses and sweat production were assessed in two age groups (≥9 years and ≥16 years) – asdd/asdd-c items were scored as a weekly average of daily responses; at least 4 days of daily data were required for analysis – weekly impact items and pgic were included to evaluate construct validity psychometric evaluation • potential floor and ceiling effects and nonresponse bias were evaluated based on both summary statistics and graphical techniques • test-retest reliability was evaluated through the computation of intraclass correlation coefficients (iccs) between week 3 and week 4; a value ≥0.70 was considered acceptable • construct validity was evaluated at week 4 based on correlations between asdd/asdd-c item 2 and asdd items related to the impact and bother of sweating (items 3 and 4, respectively), hdss, sweat production, and other pro measures as available • all statistical tests were two-tailed using a type i error rate of 1% (alpha=0.01) table 1. axillary hyperhidrosis patient measures (ahpm)a axillary sweating daily diary (asdd)b instructions: the questions in the diary are designed to measure the severity and impact of any underarm sweating you have experienced within the previous 24 hour period, including nighttime hours. while you may also experience sweating in other locations on your body, please be sure to think only about your underarm sweating when answering these questions. please complete the diary each evening before you go to sleep. item 1 [gatekeeper] during the past 24 hours, did you have any underarm sweating? yes/no when item 1 is answered “no,” item 2 is skipped and scored as zero item 2 during the past 24 hours, how would you rate your underarm sweating at its worst?0 (no sweating at all) to 10 (worst possible sweating) item 3 during the past 24 hours, to what extent did your underarm sweating impact your activities? 0 (not at all), 1 (a little bit), 2 (a moderate amount), 3 (a great deal), 4 (an extreme amount) item 4 during the past 24 hours, how bothered were you by your underarm sweating? 0 (not at all bothered), 1 (a little bothered), 2 (moderately bothered), 3 (very bothered), 4 (extremely bothered) axillary sweating daily diary-children (asdd-c)c instructions: these questions measure how bad your underarm sweating was last night and today. please think only about your underarm sweating when answering these questions. please complete these questions each night before you go to sleep. item 1 [gatekeeper] thinking about last night and today, did you have any underarm sweating? yes/no when item 1 is answered “no,” item 2 is skipped and scored as zero item 2 thinking about last night and today, how bad was your underarm sweating? 0 (no sweating at all) to 10 (worst possible sweating) weekly impact itemsb instructions: please respond “yes” or “no” to each of the following questions. a. during the past 7 days, did you ever have to change your shirt during the day because of your underarm sweating? yes/ no b. during the past 7 days, did you ever have to take more than 1 shower or bath a day because of your underarm sweating? yes/ no c. during the past 7 days, did you ever feel less confident in yourself because of your underarm sweating? yes/ no d. during the past 7 days, did you ever feel embarrassed by your underarm sweating? yes/no e. during the past 7 days, did you ever avoid interactions with other people because of your underarm sweating? yes/ no f. during the past 7 days, did your underarm sweating ever keep you from doing an activity you wanted or needed to do? yes/ no patient global impression of change (pgic) itemb overall, how would you rate your underarm sweating now as compared to before starting the study treatment? 1 (much better), 2 (moderately better), 3 (a little better), 4 (no difference), 5 (a little worse), 6 (moderately worse), 7 (much worse) aasdd/asdd-c item 2 is a validated pro measure bfor use in patients ≥16 years of age cfor use in patients ≥9 to < 16 years of age results • the pooled phase 3 study population (n=697) included 665 patients who were ≥16 years of age and 32 patients who were ≥9 to <16 years of age (table 2) table 2. demographic characteristics: atmos-1 and atmos-2 pooled population characteristic age ≥9 years (n=697) age ≥16 years (n=665) age (years), mean ± sd 32.7 ± 11.4 33.6 ± 10.9 axillary hyperhidrosis history (years), mean ± sd 15.5 ± 10.8 16.1 ± 10.7 female, n (%) 371 (53.2) 344 (51.7) white, n (%) 570 (81.8) 544 (81.8) • the response distribution for the asdd/asdd-c axillary sweating severity item (item 2) demonstrated no floor or ceiling effect, and no nonresponse bias (table 3) • construct validity was supported by strong correlations between asdd item 2 and the asdd items addressing the impact and bother of axillary sweating (items 3 and 4, respectively) (table 3) • test-retest reliability was supported by iccs of 0.93 for both age subgroups (table 3), which is well above the 0.70 criterion, and within the confidence interval of the phase 2 estimate of 0.91 (95% ci: 0.87, 0.94)4 • the asdd/asdd-c item 2 responsiveness, or ability to detect change in sweating severity, was demonstrated by large effect sizes and correlations that were within the expected range for the change in asdd/asdd-c item 2 and the change in the gravimetric measures of sweat production (table 3) table 3. asdd/asdd-c axillary sweating severity item (item 2) measurement properties measurement property age ≥9 years (n=593a) age ≥16 years (n=568a) response distribution, mean ± sd [median] baseline 7.2 ± 1.6 [ 7.3] 7.2 ± 1.3 [ 7.3] week 4 3.3 ± 2.8 [ 2.5] 3.2 ± 2.7 [ 2.4] change -3.9 ± 2.7 [-3.9] -4.0 ± 2.7 [-4.0] construct validity, pearson r asdd item 3 (impact) week 4 —b 0.89 asdd item 4 (bother) —b 0.91 sweat productionc 0.26d 0.25d test-retest reliability, icc week 4-week 3 0.93 0.93 responsiveness sweat production,c r week 4-baseline 0.23d,e 0.22d,e effect size of change (sd baseline units) -2.4 -2.4 standardized response mean -1.4 -1.5 ᵃsubjects with baseline and week 4 scores basdd-c (for use in patients <16 years of age) does not include items corresponding to asdd items 3 and 4 cmeasured gravimetrically ᵈspearman correlation coefficient ᵉbased on the change from baseline to week 4 in asdd item 2 scores and the natural logarithm of sweat production asdd, axillary sweating daily diary; icc, intraclass correlation; sd, standard deviation conclusions • the current study confirms and extends the psychometric evidence supporting the asdd/asdd-c as a new pro measure developed according to current regulatory standards • the psychometric findings presented here continue to support use of the asdd/asdd-c axillary sweating severity item (item 2) as an endpoint in assessing the efficacy of treatments for patients with axillary hyperhidrosis references 1. doolittle et al. arch dermatol res. 2016;308(10):743-9. 2. bahar et al. j am acad dermatol. 2016;75(6):1126-33. 3. guidance for industry: patient-reported outcome measures: use in medical product development to support labeling claims. fda; 2009. 4. glaser et al. poster presentation at: 13th annual maui derm for dermatologists; march 20-24, 2017; maui, hi. acknowledgements the authors would like to thank diane ingolia and christine conroy, from dermira, inc., for their work developing the pro questionnaire. this study was funded by dermira, inc. medical writing support was provided by prescott medical communications group (chicago, il). all costs associated with development of this poster were funded by dermira, inc. author disclosures dag: consultant and investigator for dermira, inc. ah: consultant for dermira, inc.; employee of the university of texas medical school, houston, which received compensation from dermira, inc. for study participation. dd, ln, sf: employees of rti health solutions. jd: employee of dermira, inc. dmp: consultant and investigator for dermira, inc. fc17posterdermiraglaserconfirmatorypsychometric.pdf skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 29 original research diagnostic approach to patients with chronic pruritus of unknown origin: a single-site retrospective chart review roselyn kellen stanger, md1, kathryn tan, md1, mark g lebwohl, md1 1department of dermatology. icahn school of medicine at mount sinai hospital, new york, ny pruritus is one of the most common symptoms in dermatology, 1 especially in elderly patients. 2 chronic pruritus (defined as itching for at least 6 weeks) is estimated to have a prevalence of almost 17% in adults 3 but likely greater than 50% patients over the age of 65. 4 chronic pruritus is associated with a “markedly reduced quality of life” 5 that is not to be underestimated. in fact, living with chronic itch is comparable to living with chronic pain. 6 hemodialysis patients with moderate to severe pruritus were more likely to feel drained, have poor sleep quality, and to have physiciandiagnosed depression. 7 pruritus in psoriasis patients is associated with agitation, depression, difficulty concentrating, and anxiety. 8 generalized pruritus without any primary skin lesions can be due to underlying systemic disorders or deemed idiopathic. 9 various terms have been used to describe these patients, including chronic idiopathic pruritus, chronic pruritus of unknown origin, 10 generalized pruritus of unknown origin, 9 and willian’s itch. 11 recently, kim et al. recommended the use of the term chronic pruritus of unknown origin (cpuo) as it would encompass the diverse array of patients with chronic itch. 10 in 2018, the british association of dermatologists (bad) published guidelines detailing the abstract background: patients with generalized pruritus lacking primary skin lesions are typically subjected to extensive laboratory tests. for many, the results fail to reveal any clinically significant findings; the british association of dermatologists published detailed guidelines for the work-up and management of these patients. our objectives were twofold: to evaluate the clinical utility of the diagnostic approach used in our practice, and to ascertain how closely we adhered to the suggested guidelines. methods: we conducted a retrospective chart review of 106 adult patients who presented with generalized pruritus without primary skin lesions. results: while 82.1% of patients received at least a complete blood count, far fewer received serum ferritin (23.6%) or chest imaging (36.8%). almost 11% of patients responded to empiric anti-scabetic treatment. approximately 9% of the skin biopsies were consistent with bullous pemphigoid. one patient had resolution of their pruritus after discontinuing an angiotensin-converting-enzyme inhibitor. conclusion: in conclusion, dermatologists should consider empiric anti-scabetic treatment, skin biopsies for patients over the age of 65, and discontinuation of an angiotensin-converting-enzyme inhibitor enzyme. introduction skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 30 recommended work-up (and treatment) of cpuo, which is as follows: detailed history, detailed examination, ferritin, full blood count, urea and electrolytes, liver function tests, erythrocyte sedimentation rate (or creactive protein if unavailable), and chest xray. 9 the guidelines specifically state that patients “should not undergo routine endocrine investigations (including thyroid function tests) unless they present with additional clinical features suggesting diabetes, other endocrinopathy or renal disease.” 9 recently, patel et al. recommended a skin biopsy for such patients as the presence of peripheral or tissue eosinophilia can help guide treatment strategies. 12 the purpose of our study was to evaluate the clinical utility of the diagnostic approach used in our practice for patients who presented with generalized pruritus lacking primary skin lesions. of note, while most patients were not ultimately diagnosed with cpuo, we would like to demonstrate that empiric treatment for scabies and performing biopsies to rule out bullous pemphigoid are worth considering in the diagnostic work-up. irb approval was obtained for this study. patients with pruritus were identified using the following icd-10 billing codes: l29.9 (pruritus, unspecified), l28.2 (other prurigo), l28.1 (prurigo nodularis) from december 2016 until august 2018. patients were excluded if they had primary skin lesions, a diagnosis of atopic dermatitis at presentation to the authors, if they were pregnant, or if they were younger than 18 years of age. patients with recent diagnoses of scabies or arthropod infection (within 6 months) were also excluded. inclusion criteria included patients with generalized pruritus of at least 6 weeks duration. generalized was defined as pruritus affecting at least 5 body parts (eg: 2 arms, 2 legs, and head) or the patient reporting that the pruritus was of a generalized nature. patients with xerosis were included if they failed at least a 2-week trial of topical corticosteroids and emollients. patients with prurigo nodularis were included if patients reported pruritus and if the lesions affected at least 5 body parts. patients with generalized prurigo nodularis that were asymptomatic were not included in the study. 576 patient charts were identified using the billing codes above, of which 106 met our inclusion and exclusion criteria. there were 54 men and 52 women, with an average age of 68.4 years for males and 67.13 years for females. the duration of pruritus ranged from 6.5 weeks to greater than 18 years. 75 of the patients presented with either xerosis or generalized excoriations, while 31 patients had erythematous papules with or without excoriations, consistent with prurigo nodularis. table 1 summarizes the percentage of patients that received the minimum work-up recommended the british association of dermatologists. bloodwork was either ordered, documented as reviewed by the dermatologist, or documented as being done by an outside provider, for 92/106 patients (86.8%). with regards to four of these 92 patients, it was documented that laboratory tests were reviewed, but we do not know which exact labs were ordered. one of the 92 patients was supposed to fax over results but the results were not visible in the chart. thus, we were able to confirm a complete blood count (cbc) was performed in a total of 87/106 patients, of which all had a cbc methods results skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 31 with differential except for two patients. 85/106 had serum urea, 79/106 had liver function tests, 25/106 had serum ferritin, and 39/106 had either a chest x-ray or chest computed-tomography (ct) done within the past 12 months prior to the visit for pruritus. in our dermatology practice, aside from obtaining bloodwork, patients commonly received empiric treatment for scabies. as demonstrated in table 2, a total of 55/106 patients were treated with either topical permethrin and/or oral ivermectin. 6/55 patients (10.9%) returned for follow-up visits with documented resolution of the pruritus. we then analyzed how many patients had received skin biopsies before or after presentation to the authors. the objective of the biopsies was primarily to rule out bullous pemphigoid (bp) or help confirm a diagnosis of prurigo nodularis. 28 patients received a biopsy for hematoxylin and eosin (h&e) as well as direct immunofluorescence (dif), whereas 24 patients only had one biopsy for h&e. 5/54 patients who received skin biopsies had findings that could be consistent with bullous pemphigoid. of note, medication switches were documented in 8/106 patients and 1/8 patients had resolution of their pruritus after switching an angiotensin-converting-enzyme inhibitor (acei) to an angiotensin-receptor-blocker (arb). table 3 compares the work-up for patients who presented with prurigo nodularis compared to patients that did not have any skin lesions. in our study, the percentage of patients who received at least a cbc was similar in the patients with and without prurigo nodularis (80.7% vs 81.3%). in contrast, a higher percentage of prurigo nodularis patients were treated empirically for scabies (61.3% vs 49.3). yet, 4/6 patients with confirmed scabies did not present with prurigo nodularis. furthermore, a higher percentage of prurigo nodularis patients had skin biopsies performed (58.1% vs 44.0%), yet none of the five patients who were ultimately diagnosed with bp had presented with prurigo nodularis. in summary, table 4 demonstrates our approach. for the initial set of bloodwork, only cbc and cmp are ordered, with further tests done as needed. the use of serum ferritin is somewhat questionable as patients with iron deficiency anemia can have falsely elevated ferritin levels as it is an acute phase reactant. 9 in addition, if iron deficiency is suspected despite normal ferritin levels, the guidelines recommend ordering additional iron panel labs such as serum iron and total iron binding capacity. 9 with regards to chest imaging, chronic pruritus has a known association with malignancy, especially leukemia and lymphoma, and can occasionally precede the diagnosis by years. 13 although we did not observe any patients with lymphoma in our study, we were limited by the duration of follow-up, and therefore we do routinely order chest x-rays. medication history must be carefully reviewed as many drugs have been associated with pruritus. 4 although only one patient in our study had resolution of their pruritus after lisinopril was discontinued, there have been several over the years in our practice. we believe that an empiric trial of antiscabetic treatment, both safe and inexpensive, is warranted in almost every patient. patients may need more than one treatment of permethrin and may require oral ivermectin. as demonstrated in table 2, discussion skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 32 table 1. laboratory and imaging recommended by the british association of dermatologists cbc urea and electrolytes liver function tests ferritin esr or crp cxr or chest ct number of patients (%) 87/106 (82.1%) 85/106 (80.2%) 79/106 (74.5%) 25/106 (23.6%) 25/106 (23.6%) 39/106 (36.8%) cbc: complete blood count; esr: erythrocyte sedimentation rate; crp: c-reactive protein; cxr: chest x-ray; ct: computed-tomography table 2. clinical utility of approach utilized in our practice. permethrin or oral ivermectin skin biopsy (h&e and/or dif) medication switch number of patients (%) 55/106 (51.9%) 54/106 (50.9%) 8/106 (7.5%) clinical utility (%) 6/55 (10.9%) patients responded to empiric treatment for scabies 5/54 (9.3%) patients had a biopsy consistent with bullous pemphigoid 1/8 (12.5%) patient with resolution of pruritus after switching lisinopril to losartan h&e: hematoxylin and eosin; dif: direct immunofluorescence table 3. work-up approach in patients with and without prurigo nodularis patients who received at minimum a cbc patients treated empirically for scabies patients who received a skin biopsy patients with prurigo nodularis (n=31) 25/31 (80.7%) 19/31 (61.3%) 18/31 (58.1%) patients with no skin lesions (n=75) 62/75 (81.3%) 37/75 (49.3%) 33/75 (44.0%) cbc: complete blood count table 4. approach to the patient with generalized idiopathic pruritus lacking primary skin lesions careful review of past medical history careful review of medications; consider switching acei to arb careful physical examination including lymph nodes cbc, cmp, chest x-ray empiric permethrin if patients fail anti-scabetic treatment and > age 65: two skin biopsies (h&e and dif) acei: angiotensin-converting-enzyme inhibitor; arb: angiotensin-receptor blocker; cbc: complete blood count; cmp: complete metabolic panel; h&e: hematoxylin and eosin; dif: direct immunofluorescence almost 11% of patients treated empirically for scabies had documented resolution of their pruritus. of note, the duration of pruritus for these patients was typically in the order of weeks to months. dermatologists must have a high index of suspicion for scabies in all elderly patients; even if living independently they may have exposure to family or friends in long-term care facilities. 14 furthermore, the clinical presentation in elderly patients can be atypical and involve the face or spare the fingerwebs. 14 treatment with topical permethrin alone has a high failure rate, likely secondary to physical limitations, and patients may need oral ivermectin. 14 in our cohort of six patients with confirmed scabies, two required oral ivermectin in skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 33 addition to topical permethrin, and a third patient required three treatments with topical permethrin. should patients fail empiric anti-scabetic treatment, we recommend skin biopsies in patients over the age of 60-65, as they are minimally invasive yet have marked implications for treatment and management. in our study, approximately 9% of the patients who received a biopsy had results that were consistent with bullous pemphigoid. the average age of these patients was 77.4 years and the duration of pruritus ranged from 3 months to 10 years. we would like to highlight three of the patients ultimately diagnosed with bullous pemphigoid. one patient carried a diagnosis of eczema. his laboratory work-up illustrated peripheral eosinophilia but normal serum levels of immunoglobulin e, yet he did not present with eczematous lesions. he had failed oral anti-histamines, oral gabapentin, and narrow-band ultraviolet b. a second patient had a diagnosis of essential thrombocythemia, which itself is associated with severe, generalized pruritus. 15 a third patient had a low level of serum thyroidstimulating-hormone level. there is conflicting evidence regarding the association between generalized pruritus and thyroid disorders and empiric testing for thyroid disorders in the absence of symptoms is not recommended. 9 of note, two patients in our study had false positive serology results for auto-antibodies to bullous pemphigoid as their biopsy results were negative, thus stressing the importance of obtaining tissue samples. indeed, in a study of 337 patients without bullous pemphigoid, 25 (7.4%) tested positive for autoantibodies to bullous pemphigoid antigen ii (bp180) and/or bullous pemphigoid antigen i (bp230), with negative results by indirect immunofluorescence. 16 with regards to discontinuation of medications, there are published reports about the association between calcium channel blockers and chronic eczematous dermatoses, 17 yet in our experience, we have had more success with the discontinuation of acei. there are several weaknesses and limitations to our study. first and foremost, the information gleaned from a retrospective chart review is not always complete. for example, patients without documented laboratory or biopsy results may have had such tests performed at outside doctors. with regards to the patients who responded to anti-scabetic treatment, we were not able to document scabies objectively. in addition, it is possible that the same treatments could have unforeseen effects on demodex, which would also alleviate itch. furthermore, there may have been a placebo response. with regards to the patients ultimately diagnosed with bullous pemphigoid, we acknowledge that bullous pemphigoid is a clinical diagnosis supported by laboratory findings. in our practice, we have had patients who, following a positive dif with no skin lesions, subsequently developed bullae. we acknowledge that others would not give them a diagnosis of bullous pemphigoid and would simply say they had a positive dif. in addition, although the nature of our study precluded us from being able to do the following – it would be of interest to ask the patient what they consider to be the cause of their pruritus. doing so may elicit helpful clues from the patient, but could also, in certain circumstances, point towards a diagnosis such as delusions of parasitosis. another weakness of this study is the lack of long-term follow-up, most relevant to finding out whether patients developed underlying skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 34 medical disorders such as bullous pemphigoid, atopic dermatitis, or other underlying medical reasons that could explain the development of generalized pruritus. this information would best be garnered from a prospective study. generalized pruritus is a common chief complaint and one that is often frustrating for patients and their providers. the guidelines published by the british association of dermatologists provide a clinical approach for patients who lack primary skin lesions. the results of our study suggest that empiric treatment for scabies with topical permethrin should be considered as well. in addition, skin biopsies to rule out subclinical bullous pemphigoid should be considered for all patients over the age of 60-65. lastly, dermatologists may consider replacing an acei for an arb. our hope is that having more evidence-based guidelines to provide a step-by-step approach will help dermatologists and primary care physicians be well equipped to manage this common outpatient complaint. abbreviations: acei: angiotensin-converting-enzyme inhibitor bad: british association of dermatologists cbc: complete blood count chest ct: chest computed-tomography bp bullous pemphigoid h&e: hematoxylin and eosin dif: direct immunofluorescence arb: angiotensin-receptor-blocker bp180: bullous pemphigoid antigen ii bp230: bullous pemphigoid antigen i conflict of interest disclosures: mark lebwohl is an employee of mount sinai and receives research funds from: abbvie, amgen, arcutis, boehringer ingelheim, dermavant, eli lilly, incyte, janssen research & development, llc, leo pharmaceutucals, ortho dermatologics, pfizer, and ucb, inc.and is a consultant for aditum bio, allergan, almirall, arcutis, inc., avotres therapeutics, birchbiomed inc., bmd skincare, boehringeringelheim, bristol-myers squibb, cara therapeutics, castle biosciences, corrona, dermavant sciences, evelo, facilitate international dermatologic education, foundation for research and education in dermatology, inozyme pharma, kyowa kirin, leo pharma, meiji seika pharma, menlo, mitsubishi, neuroderm, pfizer, promius/dr. reddy’s laboratories, serono, theravance, and verrica, pfizer, promius/dr. reddy’s laboratories, theravance, and verrica. funding: none corresponding author: roselyn stanger, md mount sinai department of dermatology 5 east 98th street, 5th floor new york, ny, 10029 email: roselynstanger@gmail.com references: 1. reich a, stander s, szepietowski jc. pruritus in the elderly. clinics in dermatology. 2011;29(1):15-23. 2. patel t, yosipovitch g. the management of chronic pruritus in the elderly. skin therapy letter. 2010;15(8):5-9. 3. stander s, schafer i, phan nq, et al. prevalence of chronic pruritus in germany: results of a cross-sectional study in a sample working population of 11,730. dermatology (basel, switzerland). 2010;221(3):229-235. 4. berger tg, shive m, harper gm. pruritus in the older patient: a clinical reviewpruritus in the older patientpruritus in the older patient. jama. 2013;310(22):2443-2450. 5. yosipovitch g, bernhard jd. chronic pruritus. new england journal of medicine. 2013;368(17):1625-1634. 6. kini sp, delong lk, veledar e, mckenziebrown am, schaufele m, chen sc. the impact of pruritus on quality of life: the skin equivalent of pain. archives of dermatology. 2011;147(10):1153-1156. 7. pisoni rl, wikstrom b, elder sj, et al. pruritus in haemodialysis patients: international results from the dialysis outcomes and practice patterns study (dopps). nephrology, dialysis, transplantation : official publication of the conclusion mailto:roselynstanger@gmail.com skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 35 european dialysis and transplant association european renal association. 2006;21(12):3495-3505. 8. yosipovitch g, goon a, wee j, chan yh, goh cl. the prevalence and clinical characteristics of pruritus among patients with extensive psoriasis. br j dermatol. 2000;143(5):969-973. 9. millington gwm, collins a, lovell cr, et al. british association of dermatologists' guidelines for the investigation and management of generalized pruritus in adults without an underlying dermatosis, 2018. br j dermatol. 2018;178(1):34-60. 10. kim bs, berger tg, yosipovitch g. chronic pruritus of unknown origin (cpuo): uniform nomenclature and diagnosis as a pathway to standardized understanding and treatment. journal of the american academy of dermatology. 2019;81(5):1223-1224. 11. ward jr, bernhard jd. willan's itch and other causes of pruritus in the elderly. international journal of dermatology. 2005;44(4):267-273. 12. patel sp, khanna r, kwatra sg. proposing a stratification scheme for chronic pruritus of unknown origin nomenclature based on presence of eosinophilia: implications for therapeutics and cohort homogeneity for clinical trials. journal of the american academy of dermatology. 13. yosipovitch g. chronic pruritus: a paraneoplastic sign. dermatologic therapy. 2010;23(6):590-596. 14. berger tg, steinhoff m. pruritus in elderly patients--eruptions of senescence. seminars in cutaneous medicine and surgery. 2011;30(2):113-117. 15. mesa ra. itchy mast cells in mpns. blood. 2009;113(23):5697-5698. 16. wieland cn, comfere ni, gibson le, weaver al, krause pk, murray ja. antibullous pemphigoid 180 and 230 antibodies in a sample of unaffected subjects. archives of dermatology. 2010;146(1):21-25. 17. summers em, bingham cs, dahle kw, sweeney c, ying j, sontheimer rd. chronic eczematous eruptions in the aging: further support for an association with exposure to calcium channel blockers. jama dermatol. 2013;149(7):814-818. poster presented at the 36th fall clinical dermatology conference | las vegas, nv | october 12-15, 2017 certolizumab pegol for the treatment of chronic plaque psoriasis: dlqi and wpai patient-reported outcomes from two ongoing phase 3, multicenter, randomized, placebo-controlled studies (cimpasi-1 and cimpasi-2) diamant thaçi,1 alice b. gottlieb,2 kristian reich,3 jerry bagel,4 daniel burge,5 luke peterson,6 janice drew,5 catherine arendt,7 jolanta węgłowska8 1university of lübeck, lübeck, germany; 2new york medical college, valhalla, ny; 3dermatologikum hamburg and sciderm research institute, hamburg, germany; 4psoriasis treatment center of central new jersey, east windsor, nj; 5dermira, inc., menlo park, ca; 6ucb biosciences, inc., raleigh, nc; 7ucb pharma, brussels, belgium; 8niepubliczny zakład opieki zdrowotnej multimedica, wrocław, poland introduction • psoriasis affects ~3% of adults in the us and ~2-6% in europe,1-3 and most patients develop the disease in the third decade of life4 • the correlation between psoriasis and reduced quality of life has been well-documented,5-7 with more severe forms of the disease associated with greater reduction in quality of life5 • psoriasis is negatively correlated with work productivity, and patients with more severe disease experience increased productivity loss8-10 • certolizumab pegol (czp) is the only pegylated, fc-free, anti-tumor necrosis factor (tnf) biologic currently under development for the treatment of moderate-to-severe chronic plaque psoriasis and has demonstrated efficacy and safety in previous psoriasis trials11,12 • cimpasi-1 (nct02326298) and cimpasi-2 (nct02326272) are ongoing phase 3 trials designed to assess the efficacy and safety of czp compared with placebo; patient-reported quality of life and work productivity from the first 48 weeks of these studies are presented here methods study design • cimpasi-1 and cimpasi-2 are replicate, phase 3, randomized, double-blind, placebo-controlled, multicenter studies conducted in north america and europe • patients were randomized 2:2:1 to czp 400 mg every 2 weeks (q2w), czp 200 mg q2w (following 400 mg loading dose at weeks 0, 2, and 4), or placebo q2w for 16 weeks (figure 1) • at week 16, patients continued to receive treatment through week 48 according to the following criteria: – czp 400 mg q2wand czp 200 mg q2w-treated psoriasis area and severity index (pasi) 50 responders (≥50% reduction in pasi) continued to receive their initial blinded treatment – placebo-treated week 16 pasi 75 responders (≥75% reduction in pasi) continued blinded placebo treatment; pasi 50-75 responders (≥50% but <75% reduction in pasi) received czp 200 mg q2w (following 400 mg loading dose at weeks 16, 18, 20) – week 16 pasi 50 nonresponders entered the escape arm and received unblinded czp 400 mg q2w • pasi 50 nonresponders at week 32, 40, or 48 were withdrawn from the study figure 1. study design 0 randomization 16 484032week initial treatment period (double-blind) maintenance period (double-blind)screening 1:2:2 2 4 placebo q2w ld ≥ pasi 75 ld pasi 50-75 < pasi 50-withdrawn < pasi 50-withdrawn < pasi 50-withdrawn < pasi 50-withdrawn < pasi 50 < pasi 50 < pasi 50 czp 200 mg q2w czp 400 mg q2w escape czp 400 mg q2w czp, certolizumab pegol; ld, czp 400 mg loading dose at weeks 0, 2, and 4 or weeks 16, 18, and 20; pasi 50, ≥50% reduction in psoriasis area and severity index (pasi); pasi 50-75, ≥50% but <75% reduction in pasi; pasi 75, ≥75% reduction in pasi; q2w, every 2 weeks patients • eligible patients were ≥18 years of age and had moderate-to-severe psoriasis for ≥6 months (pasi ≥12, affected body surface area [bsa] ≥10%, physician’s global assessment [pga; 5-point scale] ≥3) • patients had to be candidates for systemic psoriasis therapy, phototherapy, and/or photochemotherapy • patients were excluded if they had previous treatment with czp or with >2 biologics (including anti-tnf); had history of primary failure to any biologic or secondary failure to >1 biologic; had erythrodermic, guttate, or generalized pustular psoriasis types; or had history of current, chronic, or recurrent viral, bacterial, or fungal infections quality of life and work productivity assessments • mean change from baseline (cfb) in dermatology life quality index (dlqi) at week 16 (secondary endpoint) and week 48 were assessed • dlqi minimal clinically important difference (mcid; ≥4-point improvement13) responder rate, dlqi 0/1 (absolute score ≤1) responder rate, and cfb in work productivity and activity impairment questionnaire-specific health problem (wpai) at week 16 and week 48 were also assessed • negative cfb values for dlqi and wpai signify improvement statistical analysis • efficacy analyses were performed on the randomized set (all randomized patients) • inferential statistics for cfb in dlqi at week 16 were based on an analysis of covariance (ancova) model with treatment group, region, and prior biologic exposure (yes/no) as factors and baseline dlqi score as a covariate; a similar ancova model (substituting baseline dlqi with baseline wpai score as a covariate) was used to calculate inferential statistics for cfb in wpai at week 16 • mean cfb values are reported for continuous variables, and percentages are reported for responder variables • last observation carried forward (locf) was used to impute missing data for cfb in dlqi (week 16 and week 48) and wpai (week 16); nonresponse imputation was used for dlqi mcid and dlqi 0/1; cfb in wpai at week 48 was based on observed cases • week 16 pasi 50 nonresponders had week 16 values carried forward to week 48; all other missing data during the maintenance period were imputed using locf except for categorical endpoint data which were imputed as nonresponders • last observation carried forward (locf) was used to impute missing data for cfb in dlqi (week 16 and week 48) and wpai (week 16); nonresponse imputation was used for dlqi mcid and dlqi 0/1; cfb in wpai at week 48 was based on observed cases • week 16 pasi 50 nonresponders had week 16 values carried forward to week 48; all other missing data during the maintenance period were imputed using locf except for categorical endpoint data which were imputed as nonresponders results patient disposition, demographics, and baseline characteristics • in cimpasi-1|cimpasi-2, 88|87 patients were randomized to czp 400 mg q2w, 95|91 to czp 200 mg q2w, and 51|49 to placebo (figure 2) • in both studies, at least 90% of patients in each treatment arm completed week 16 (figure 2) • of those patients who entered the maintenance period in cimpasi-1|cimpasi-2, 90.9%|88.4% of czp 400 q2w patients and 95.9%|84.2% of czp 200 mg q2w patients completed week 48 (figure 2) • baseline dlqi scores were comparable across treatment groups for both studies while wpai score trends varied slightly by study (table 1) figure 2. patient disposition completed wk 16 cimpasi-1 cimpasi-2screened n=286 randomized n=234 screened n=301 randomized n=227 placebo n=51 n=46 (90.2%) discontinued 5 adverse event 0 lack of efficacy 1 protocol violation 0 lost to follow-up 1 consent w/d 3 other 0 discontinued 3 adverse event 0 lack of efficacy 0 protocol violation 0 lost to follow-up 1 consent w/d 2 other 0 discontinued 1 adverse event 1 lack of efficacy 0 protocol violation 0 lost to follow-up 0 consent w/d 0 other 0 discontinued 4 adverse event 0 lack of efficacy 0 protocol violation 0 lost to follow-up 1 consent w/d 3 other 0 discontinued 7 adverse event 3 lack of efficacy 0 protocol violation 0 lost to follow-up 2 consent w/d 2 other 0 discontinued 4 adverse event 1 lack of efficacy 0 protocol violation 0 lost to follow-up 0 consent w/d 1 other 2 czp 200 mg q2w n=95 ≥pasi 50 and entered maintenance completed wk48 discontinued 3 consent w/d 1 other 1 <pasi 50 1 n=74 discontinued 7 lost to follow-up 1 consent w/d 3 other 1 <pasi 50 2 n=5a n=3a discontinued 12 adverse event 3 lack of efficacy 2 lost to follow -up 2 consent w/d 3 <pasi 50 2 discontinued 8 adverse event 4 lack of efficacy 1 consent w/d 1 other 1 <pasi 50 1 discontinued 1 consent w/d 1 discontinued 2 adverse event 2 n=77c czp 400 mg q2w n=88 placebo n=49 czp 200 mg q2w n=91 czp 400 mg q2w n=87 n=92 (96.8%) n=87 (98.9%) n=87 (98.9%) escapeb n=38 escapeb n=38 escapeb n=18 escapeb n=18 escapeb n=8 escapeb n=8 escapeb n=34 escapeb n=34 escapeb n=8 escapeb n=8 escapeb n=12 escapeb n=12 n=70 (90.9%) n=70 (90.9%) n=5 (100%) n=5 (100%) n=3 (100%) n=3 (100%) n=71 (95.9%) n=71 (95.9%) n=45 (91.8%) n=76n=5a n=6a n=69d n=84 (92.3%) n=83 (95.4%) n=83 (95.4%) n=61 (88.4%) n=61 (88.4%) n=3 (60.0%) n=3 (60.0%) n=5 (83.3%) n=5 (83.3%) n=64 (84.2%) n=64 (84.2%) aupon entering maintenance period, placebo-treated pasi 75 responders (≥75% reduction in pasi) continued blinded placebo treatment; pasi 50-75 responders (≥50% but <75% reduction in pasi) received czp 200 mg q2w bpasi 50 nonresponders at week 16 received open-label czp 400 mg q2w in the escape arm of the study c 2 patients completed week 16 but did not enter maintenance period due to adverse events d2 patients completed week 16 but did not enter maintenance period (1 loss to follow-up; 1 consent withdrawn) czp, certolizumab pegol; pasi 50, 50% reduction in psoriasis area and severity index (pasi); q2w, every 2 weeks; w/d, withdrawn table 1. patient demographics and baseline disease characteristics cimpasi-1 cimpasi-2 placebo (n=51) czp 200 mg q2w (n=95) czp 400 mg q2w (n=88) placebo (n=49) czp 200 mg q2w (n=91) czp 400 mg q2w (n=87) demographics age (years), mean ± sd 47.9 ± 12.8 44.5 ± 13.1 43.6 ± 12.1 43.3 ± 14.5 46.7 ± 13.3 46.4 ± 13.5 male, n (%) 35 (68.6) 67 (70.5) 60 (68.2) 26 (53.1) 58 (63.7) 43 (49.4) white, n (%) 45 (88.2) 87 (91.6) 79 (89.8) 44 (89.8) 86 (94.5) 81 (93.1) geographic region, n (%) north america europe 26 (51.0) 25 (49.0) 49 (51.6) 46 (48.4) 45 (51.1) 43 (48.9) 35 (71.4) 14 (28.6) 61 (67.0) 30 (33.0) 61 (70.1) 26 (29.9) weight (kg), mean ± sd 95.2 ± 19.5 92.6 ± 21.0 92.2 ± 21.7 87.1 ± 26.4 97.8 ± 25.6 91.8 ± 27.7 bmi (kg/m2), mean ± sd 32.2 ± 6.8 31.1 ± 7.3 30.7 ± 6.7 30.2 ± 8.0 32.8 ± 8.3 31.7 ± 8.9 baseline disease characteristics duration of psoriasis at screening (years), mean ± sd 18.5 ± 12.9 16.6 ± 12.3 18.4 ± 12.9 15.4 ± 12.2 18.8 ± 13.5 18.6 ± 12.4 concurrent psa (self-reported), n (%) 4 ( 7.8) 10 (10.5) 15 (17.0) 9 (18.4) 22 (24.2) 26 (29.9) pasi score, mean ± sd 19.8 ± 7.5 20.1 ± 8.2 19.6 ± 7.9 17.3 ± 5.3 18.4 ± 5.9 19.5 ± 6.7 bsa affected (%), mean ± sd 26.1 ± 16.1 25.4 ± 16.9 24.1 ± 16.6 20.0 ± 9.5 21.4 ± 12.2 23.1 ± 11.6 prior biologic use,a n (%) anti-tnf anti-il17 15 (29.4) 10 (19.6) 3 ( 5.9) 30 (31.6) 19 (20.0) 8 ( 8.4) 29 (33.0) 17 (19.3) 4 ( 4.5) 14 (28.6) 9 (18.4) 2 ( 4.1) 32 (35.2) 22 (24.2) 8 ( 8.8) 30 (34.5) 22 (25.3) 4 ( 4.6) dlqi, mean ± sd 13.9 ± 8.3 13.3 ± 7.4 13.1 ± 6.5 12.9 ± 7.3 15.2 ± 7.2 14.2 ± 7.2 wpai domain scores, mean ± sd absenteeism presenteeism work productivity loss work activity impairment 5.2 ± 12.2 21.9 ± 25.5 24.5 ± 28.1 28.8 ± 25.1 2.3 ± 7.5 19.3 ± 25.6 20.6 ± 26.9 29.2 ± 28.0 5.2 ± 18.4 20.3 ± 25.0 24.4 ± 29.1 33.6 ± 28.8 2.5 ± 7.0 15.3 ± 17.4 16.8 ± 19.0 31.0 ± 26.6 7.0 ± 22.4 20.0 ± 25.8 25.9 ± 31.5 36.8 ± 32.7 1.3 ± 4.5 18.8 ± 19.8 19.3 ± 20.4 33.6 ± 28.9 apatients may have had exposure to >1 prior biologic but ≤2 per exclusion criteria bmi, body mass index; bsa, body surface area; czp, certolizumab pegol; dlqi, dermatology life quality index; il, interleukin; pasi, psoriasis area and severity index; pga, physician’s global assessment; psa, psoriatic arthritis; q2w, every 2 weeks; tnf, tumor necrosis factor; wpai, work productivity and activity impairment questionnaire-specific health problem patient-reported outcomes dlqi • at week 16, mean cfb in dlqi demonstrated greater improvement for both czp 400 mg q2w and 200 mg q2w vs placebo (figure 3) • improvement was maintained with both czp 400 mg q2w and 200 mg q2w at week 48 (figure 3) figure 3. dlqi mean scores at baseline, week 16, and week 48 13.9 10.9 bl wk 16 placebo (n=51) 13.3 4.4 4.5 bl wk 16 wk 48 13.1 3.5 3.4 bl wk 16 wk 48 czp 200 mg q2wa (n=95) cimpasi-1 czp 400 mg q2w (n=88) mean cfb to: wk 16 wk 48 -3.3 n/a -8.9** -8.8 -9.6** -9.8 12.9 10.0 bl wk 16 placebo (n=49) 15.2 4.1 4.5 bl wk 16 wk 48 14.2 4.3 3.4 bl wk 16 wk 48 czp 200 mg q2wa (n=91) cimpasi-2 czp 400 mg q2w (n=87) mean cfb to: wk 16 wk 48 -2.9 n/a -11.1** -10.7 -10.0** -10.9 18 16 14 12 8 6 4 10 2 0 m ea n s co re 18 16 14 12 8 6 4 10 2 0 m ea n s co re **p<0.0001 vs placebo aczp 200 mg q2w patients received loading dose of czp 400 mg at weeks 0, 2, and 4 statistical comparisons not performed at week 48 p-values at week 16 are based on adjusted least squares means from an ancova model with treatment group, region, and prior biologic exposure (yes/no) as factors and baseline dlqi score as a covariate using locf imputation week 16 pasi 50 nonresponders had week 16 values carried forward to week 48; all other missing data during the maintenance period were imputed using locf ancova, analysis of covariance; bl, baseline; cfb, change from baseline; czp, certolizumab pegol; dlqi, dermatology life quality index; locf, last observation carried forward; q2w, every 2 weeks; wk, week • dlqi mcid responder rates were greater at week 16 for czp 400 mg q2w and 200 mg q2w vs placebo (figure 4) • improvement was maintained for czp 400 mg q2w and 200 mg q2w at week 48 (figure 4) figure 4. dlqi minimal clinically important differencea responder rates through week 48 cimpasi-1 week cimpasi-2 week 80 100 60 40 20 0 r es po nd er r at e (% ) 0 2 8 12 16 24 32 48 80 100 60 40 20 0 r es po nd er r at e (% ) 0 2 8 12 16 24 32 48 placebo (n=51) czp 200 mg q2wb (n=95) czp 400 mg q2w (n=88) 41.2% 66.3% 78.4% 68.2% 60.0% placebo (n=49) czp 200 mg q2wb (n=91) czp 400 mg q2w (n=87) 40.8% 74.7% 75.9% 70.1% 61.5% a≥4-point improvement in dlqi bczp 200 mg q2w patients received loading dose of czp 400 mg at weeks 0, 2, and 4 statistical comparisons not performed at week 48 week 16 pasi 50 nonresponders were imputed as nonresponders for all subsequent time points through week 48; all other missing data were imputed via nonresponder imputation czp, certolizumab pegol; dlqi, dermatology life quality index; q2w, every 2 weeks • dlqi 0/1 responder rates were also greater at week 16 for czp 400 mg q2w and 200 mg q2w vs placebo (figure 5) • the rates were maintained for czp 400 mg q2w and 200 mg q2w at week 48 (figure 5) figure 5. dlqi 0/1 responder rates through week 48 cimpasi-1 week cimpasi-2 week 80 100 60 40 20 0 r es po nd er r at e (% ) 0 2 8 12 16 24 32 48 80 100 60 40 20 0 r es po nd er r at e (% ) 0 2 8 12 16 24 32 48 placebo (n=51) czp 200 mg q2wa (n=95) czp 400 mg q2w (n=88) 5.9% 45.5% 47.4% 52.3% 45.3% placebo (n=49) czp 200 mg q2wa (n=91) czp 400 mg q2w (n=87) 8.2% 46.2% 50.6% 50.6% 38.5% aczp 200 mg q2w patients received loading dose of czp 400 mg at weeks 0, 2, and 4 statistical comparisons not performed at week 48 week 16 pasi 50 nonresponders were imputed as nonresponders for all subsequent time points through week 48; all other missing data were imputed via nonresponder imputation czp, certolizumab pegol; dlqi, dermatology life quality index; q2w, every 2 weeks wpai • greater cfb to week 16 was observed with both czp doses compared with placebo in wpai presenteeism (reduced work effectiveness), work productivity loss, and activity impairment domains (figure 6) • wpai improvements for both czp doses were maintained at week 48 among completers (figure 7) figure 6. change from baseline in wpai domain scores at week 16 7.1 4.1 5.5 absenteeism -0.8 -8.0* -13.0* presenteeism 7.8 -4.7* -8.9* work productivity loss -0.6 -24.4** activity impairment -15.8** cimpasi-1 wpai domains -1.8 -3.2 3.7 absenteeism 2.5 -11.5*-12.8* presenteeism 1.5 -13.8 -9.1 work productivity loss -2.4 -26.4** -23.4** activity impairment cimpasi-2 wpai domains placebo (n=51) czp 200 mg q2wa (n=95) czp 400 mg q2w (n=88) placebo (n=49) czp 200 mg q2wa (n=91) czp 400 mg q2w (n=87) 20 0 -20 -40 m ea n a bs ol ut e c ha ng e fr om b as el in e (← im pr ov em en t) 20 0 -20 -40 m ea n a bs ol ut e c ha ng e fr om b as el in e (← im pr ov em en t) *p<0.05, **p<0.0001 vs placebo aczp 200 mg q2w patients received loading dose of czp 400 mg at weeks 0, 2, and 4 p-values are nominal and based on adjusted least squares means from an ancova model with treatment group, region, prior biologic exposure (yes/no) as factors and baseline wpai score as a covariate using locf imputation ancova, analysis of covariance; czp, certolizumab pegol; locf, last observation carried forward; q2w, every 2 weeks; wpai, work productivity and activity impairment questionnaire-specific health problem figure 7. change from baseline in wpai domain scores at week 48 5.9 0.3 absenteeism -7.7 -18.1 presenteeism -3.7 -17.6 work productivity loss -19.7 -31.2 activity impairment cimpasi-1 wpai domains -1.2 -0.6 absenteeism -12.4 -15.5 presenteeism -12.9 -15.0 work productivity loss -28.3 -25.7 activity impairment cimpasi-2 wpai domains czp 200 mg q2w (n=74) czp 400 mg q2w (n=77) czp 200 mg q2w (n=76) czp 400 mg q2w (n=69) m ea n a bs ol ut e c ha ng e fr om b as el in e (← im pr ov em en t) m ea n a bs ol ut e c ha ng e fr om b as el in e (← im pr ov em en t) 20 0 -20 -40 20 0 -20 -40n= 47 54 47 54 47 54 68 68 n= 42 42 42 42 42 42 64 61 statistical comparisons not performed at week 48 based on observed cases czp, certolizumab pegol; q2w, every 2 weeks; wpai, work productivity and activity impairment questionnaire-specific health problem conclusions • treatment with czp 400 mg q2w or czp 200 mg q2w was associated with significant, clinically meaningful improvements in quality of life (dlqi) and work productivity (wpai) versus placebo at week 16 • improvements in quality of life and work productivity were maintained through week 48 with continued czp 400 mg q2w or czp 200 mg q2w treatment • for most measures, improvements were numerically greater in patients receiving czp 400 mg q2w than in those receiving czp 200 mg q2w references 1. rachakonda et al. j am acad dermatol. 2014;70(3):512-6. 2. kurd et al. j am acad dermatol. 2009;60(2):218-24. 3. danielsen et al. br j dermatol. 2013;168(6):1303-10. 4. farber et al. dermatologica. 1974;148(1):1-18 5. gelfand et al. j am acad dermatol. 2004;51(5):704-8. 6. reich et al. arch dermatol res. 2008;300(10):537-44. 7. revicki et al. dermatology. 2008;216(3):260-70. 8. armstrong et al. plos one. 2012;7(12):e52935. 9. korman et al. dermatol online j. 2016;22(7):pii: 13030/qt4vb7q7rr. 10. wu et al. am j clin dermatol. 2009;10(6):407-10. 11. reich et al. br j dermatol. 2012;167(1):180-90. 12. gladman et al. arthritis care res (hoboken). 2014;66(7):1085-92. 13. basra et al. dermatology. 2015;230(1):27-33. acknowledgements this study and all costs associated with the development of this poster were funded by dermira, inc. dermira and ucb are in a strategic collaboration to evaluate the efficacy and safety of certolizumab pegol in the treatment of moderate-tosevere plaque psoriasis. medical writing support was provided by prescott medical communications group (chicago, il). author disclosures dt: consultant, advisory board member and speaker for: abbvie, almiral, amgen, biogen-idec, boehringer ingelheim, bristol-meyer squibb, celgene, dignity, galderma, galapagos, glaxosmithkline, janssen, leo pharma, eli lilly, maruho, medac, merck, morhphosis, novartis, regeneron, sandoz, sanofi-aventis, pfizer, ucb, xenoport. abg: consulting/ advisory board agreements: janssen, celgene, bristol-myers squibb, beiersdorf, abbvie, ucb, novartis, incyte, pfizer, lilly, xenoport, development crescendo bioscience, aclaris, amicus, reddy labs, valeant, dermira, allergan, csl behring, merck, sun pharmaceutical industries. research/educational grants: janssen, incyte. kr: speaker’s fees, honoraria, and/or advisory board: abbvie, amgen, biogen, boehringer ingelheim, celgene, centocor, covagen, forward pharma, glaxosmithkline, janssen, leo pharma, eli lilly, medac, merck, novartis, ocean pharma, pfizer, regeneron, takeda, ucb, xenoport. jb: honoraria for speaking, consultation, or clinical investigation from: amgen, abbvie, boehringer ingelheim, novartis, eli lilly, celgene, janssen, leo pharma, pfizer, valeant. db, jd: employees of dermira. lp, ca: employees of ucb. jw: investigator and/or speaker for amgen, celgene, coherus, dermira, eli lilly, galderma, janssen, leo pharma, merck, pfizer, regeneron, sandoz, ucb. fc17posterdermirathacicertolizumabpegolcimpasi-1&2.pdf objective evaluate maintenance of response rates among patients with moderate to severe plaque psoriasis receiving bkz who had an initial response (iga 0/1, bsa ≤1%, pasi 100) at week 16 of the three phase 3 feeder studies and received continuous q4w or q8w bkz maintenance dosing over two years. introduction • bimekizumab (bkz) is a monoclonal igg1 antibody that selectively binds to and inhibits both interleukin (il)-17a and il-17f.1 • in phase 3 clinical trials, bkz led to substantial clinical improvements in patients with moderate to severe plaque psoriasis, with no unexpected safety findings.2–5 • given that psoriasis is a chronic disease, it is important to understand long-term treatment efficacy. methods • patients who completed one of three phase 3 studies (be vivid: nct03370133; be sure: nct03412747; be ready: nct03410992) could enroll in the be bright (nct03598790) twoyear open-label extension (ole).1–3 these analyses include patients randomized to bkz 320 mg every 4 weeks (q4w) who responded at week 16 of the feeder study, received bkz 320 mg q4w or every 8 weeks (q8w) maintenance dosing from week 16, and enrolled in be bright (figure 1). • we report maintenance of investigator’s global assessment (iga) 0/1, psoriasis body surface area (bsa) ≤1%, and 100% improvement in the psoriasis area and severity index (pasi 100, complete skin clearance) through two years of treatment (ole week 48) among week 16 responders who received continuous bkz maintenance dosing in the ole (q4w/q4w/q4w or q4w/q8w/q8w). • missing data were imputed using modified non-responder imputation (mnri), non-responder imputation (nri), and observed case (oc). – mnri: multiple imputation was used for missing data, except for patients with missing data following treatment discontinuation due to lack of efficacy where they were considered non-responders. • safety over two years was evaluated for all patients who received ≥1 dose of bkz in the phase 3 feeder studies or the ole. – treatment-emergent adverse events (teaes) were coded using meddra v19.0. exposure-adjusted incidence rates (eairs) are the incidence of new cases per 100 patient-years (py). results • patient demographics and baseline characteristics for week 16 responders are reported in table 1. • 989 patients were initially randomized to bkz 320 mg q4w; at week 16, 87.5% achieved iga 0/1, 74.9% achieved bsa ≤1%, and 62.7% achieved pasi 100 (nri). • among week 16 iga 0/1, bsa ≤1%, and pasi 100 responders, respectively, response rates were maintained to ole week 48 with both q4w and q8w maintenance dosing regimens (figure 2). • the most common teaes (incidence >5%) were nasopharyngitis, oral candidiasis, and upper respiratory tract infection. no new safety signals were identified in the phase 3 feeder studies or the be bright ole (table 2). summary presented at the fall clinical dermatology conference 2021 | october 21–24 | las vegas, nv conclusions among week 16 responders, response rates were maintained through to two years of bkz treatment. iga 0/1, bsa ≤1%, and pasi 100 response rates were maintained with bkz with both q4w and q8w maintenance dosing regimens. among all bkz-treated patients over two years, the most frequent adverse events were nasopharyngitis, oral candidiasis, and upper respiratory tract infection, consistent with results through one year.2–4 bruce strober,1,2 akihiko asahina,3 ulrich mrowietz,4 mark lebwohl,5 peter foley,6 richard g. langley,7 jonathan barker,8 christopher cioffi,9 nancy cross,10 maggie wang,10 carle paul11 bimekizumab response maintenance through two years of treatment in patients with moderate to severe plaque psoriasis who responded after 16 weeks: interim results from the be bright open-label extension trial previously presented at aad first 2021 figure 1 be bright study design: included patients bkz: bimekizumab; bsa: body surface area; ci: confidence interval; dlqi: dermatology life quality index; eair: exposure-adjusted incidence rate; iga 0/1: score of 0 (clear) or 1 (almost clear) with ≥2-category improvement relative to baseline in investigator’s global assessment; il: interleukin; mnri: modified non-responder imputation; nri: non-responder imputation; oc: observed case; ole: open-label extension; pasi 90: ≥90% improvement from baseline in psoriasis area and severity index; pasi 100: 100% improvement from baseline in psoriasis area and severity index; py: patient-years; q4w: every 4 weeks; q8w: every 8 weeks; sd: standard deviation; teae: treatment-emergent adverse event; tnf: tumor necrosis factor. institutions: 1yale university, new haven, connecticut, usa; 2central connecticut dermatology research, cromwell, connecticut, usa; 3department of dermatology, the jikei university school of medicine, tokyo, japan; 4psoriasis-center, department of dermatology, university medical center schleswigholstein, campus kiel, germany; 5icahn school of medicine at mount sinai, new york, new york, usa; 6the university of melbourne, st. vincent’s hospital melbourne, fitzroy and probity medical research inc., skin health institute, carlton, victoria, australia; 7division of clinical dermatology and cutaneous science, dalhousie university, halifax, nova scotia, canada; 8st john’s institute of dermatology, king’s college london, london, uk; 9ucb pharma, brussels, belgium; 10ucb pharma, raleigh, north carolina, usa; 11toulouse university and chu, toulouse, france references: 1adams r et al. front immunol 2020;11:1894; 2reich k et al. lancet 2021;397:487–98; 3gordon k et al. lancet 2021;397:475–86; 4warren r et al. nejm 2021; doi: 10.1056/nejmoa2102388; 5reich k et al. nejm 2021; doi: 10.1056/nejmoa2102383. author contributions: substantial contributions to study conception/design, or acquisition/analysis/interpretation of data: bs, aa, um, ml, pf, rgl, jb, cc, nc, mw, cp; drafting of the publication, or revising it critically for important intellectual content: bs, aa, um, ml, pf, rgl, jb, cc, nc, mw, cp; final approval of the publication: bs, aa, um, ml, pf, rgl, jb, cc, nc, mw, cp. author disclosures: bs: consultant (honoraria) from abbvie, almirall, amgen, arcutis, arena, aristea, boehringer ingelheim, bristol myers squibb, celgene, dermavant, dermira, eli lilly, equillium, gsk, janssen, leo pharma, meiji seika pharma, mindera, novartis, ortho dermatologics, pfizer, regeneron, sanofi genzyme, sun pharma, and ucb pharma; speaker for abbvie, amgen, eli lilly, janssen, and ortho dermatologics; scientific director (consulting fee) for corevitas psoriasis registry; investigator for abbvie, cara therapeutics, corevitas psoriasis registry, dermavant, dermira and novartis; editor-in-chief (honorarium) for journal of psoriasis and psoriatic arthritis. aa: honoraria and/or research grants from abbvie, celgene, eisai, eli lilly, janssen, kyowa kirin, leo pharma, maruho, mitsubishi pharma, sun pharma, taiho pharma, torii pharmaceutical, and ucb pharma. um: served as advisor and/or clinical study investigator for, and/or received honoraria and/or grants from abbvie, almirall, aristea, boehringer ingelheim, celgene, dr. reddy’s laboratories, eli lilly, foamix, formycon, forward pharma, janssen, leo pharma, medac, novartis, phi-stone, pierre fabre, sanofi, and ucb pharma. ml: employee of mount sinai and receives research funds from abbvie, amgen, arcutis, avotres, boehringer ingelheim, dermavant, eli lilly, incyte, janssen research & development, llc, ortho dermatologics, regeneron, and ucb pharma; consultant for aditum bio, anaptysbio, almirall, arcutis, aristea, arrive technology, avotres therapeutics, biomx, boehringer ingelheim, bristol myers squibb, cara therapeutics, castle biosciences, corrona, dermavant sciences, dr.reddy, evelo, evommune, facilitate international dermatologic education, forte, foundation for research and education in dermatology, helsinn, leo pharma, meiji, mindera, pfizer, seanergy, and verrica. pf: grant support from abbvie, amgen, celgene, eli lilly, janssen, leo pharma, merck, novartis, pfizer, sanofi, and sun pharma; served as an investigator for abbvie, akaal, amgen, arcutis, aslan, astrazeneca, bristol myers squibb, boehringer ingelheim, botanix, celgene, celtaxsys, csl, cutanea, dermira, eli lilly, galderma, geneseq, genentech, gsk, hexima, janssen, leo pharma, medimmune, merck, novartis, pfizer, regeneron pharmaceuticals inc, reistone, roche, sanofi, sun pharma, ucb pharma, and valeant; served on advisory boards for abbvie, amgen, bristol myers squibb, boehringer ingelheim, celgene, eli lilly, galderma, gsk, janssen, leo pharma, mayne pharma, merck, novartis, pfizer, sanofi, sun pharma, ucb pharma, and valeant; served as a consultant for bristol myers squibb, eli lilly, galderma, janssen, leo pharma, mayne pharma, medimmune, novartis, pfizer, roche, ucb pharma, and wintermute; received travel grants from abbvie, eli lilly, galderma, janssen, leo pharma, merck, novartis, pfizer, roche, sun pharma, and sanofi; served as a speaker for or received honoraria from abbvie, amgen, celgene, eli lilly, galderma, gsk, janssen, leo pharma, merck, novartis, pfizer, roche, sanofi, sun pharma, and valeant. rgl: principal investigator for abbvie, amgen, boehringer ingelheim, celgene, eli lilly, leo pharma, merck, novartis, pfizer, and ucb pharma; served on scientific advisory boards for abbvie, amgen, boehringer ingelheim, celgene, eli lilly, leo pharma, merck, novartis, pfizer, and ucb pharma; provided lectures for abbvie, amgen, celgene, leo pharma, merck, novartis, and pfizer. jb: attended advisory boards and/or received consultancy fees and/or spoken at sponsored symposia and/or received grant funding from abbvie, almirall, amgen, anaptys-bio, boehringer ingelheim, bristol myers squibb, celgene, eli lilly, janssen, leo pharma, novartis, pfizer, samsung, sienna, sun pharma, and ucb pharma. cc, nc, mw: employees and shareholders of ucb pharma. cp: consulting fees and /or grants from abbvie, almirall, amgen, boehringer ingelheim, celgene, eli lilly, gsk, janssen cilag, leo pharma, novartis, pierre fabre, pfizer, sanofi regeneron, and ucb pharma. acknowledgments: this study was funded by ucb pharma. we would like to thank the patients and their caregivers in addition to all of the investigators and their teams who contributed to this study. the authors acknowledge susanne wiegratz, msc, ucb pharma, monheim, germany, for publication coordination, natalie nunez gomez, md, ucb pharma, brussels, belgium, for critical review, and evelyn turner, bsc, and claire hews, phd, costello medical, cambridge, uk, for medical writing and editorial assistance. all costs associated with development of this presentation were funded by ucb pharma. table 1 baseline demographics and disease characteristics table 2 two-year pooled safety figure 2 maintenance of response through two years (pooled; mnri, nri, oc) a) iga 0/1 b) bsa ≤1% c) pasi 100 all patients in the q4w/q8w/q8w arm achieved pasi 90 on entering the ole. abe vivid: all bkz-randomized patients continued q4w treatment at week 16;2 be sure: patients allocated to bkz treatment were randomized 1:1 at baseline to either continue q4w or switch to q8w at week 16;4 be ready: bkz-randomized week 16 pasi 90 responders were re-randomized 1:1:1 to bkz q4w, q8w, or placebo (pasi 90 non-responders entered an escape arm);3 bbe sure and be ready had a week 56 visit that was not included in the be bright pooled analysis. adata are reported for all patients with a response at week 16 who enrolled in be bright; bincludes patients with multiple prior biologic use. the data cut-off for the ongoing be bright trial was november 9, 2020. teaes were assigned to the dose most recently received prior to the date of onset of the teae. patients who received both bkz 320 mg q4w and q8w at different times in the trials are included in the population count of both treatment groups, but only once in each bkz total group. ateaes occurring in >5% patients in the bkz total group. week 16 respondersa iga 0/1 responders (n=685) bsa ≤1% responders (n=597) pasi 100 responders (n=503) age (years), mean ± sd 44.9 ± 13.4 44.9 ± 13.3 44.8 ± 13.2 male, n (%) 488 (71.2) 420 (70.4) 352 (70.0) caucasian, n (%) 591 (86.3) 513 (85.9) 441 (87.7) weight (kg), mean ± sd 89.2 ± 20.8 88.4 ± 20.3 87.8 ± 19.3 duration of psoriasis (years), mean ± sd 18.4 ± 12.4 18.3 ± 12.6 18.0 ± 12.3 pasi, mean ± sd 21.4 ± 7.6 21.1 ± 7.4 21.2 ± 7.2 bsa (%), mean ± sd 27.4 ± 15.6 26.7 ± 15.2 26.7 ± 14.9 iga, n (%) 3: moderate 451 (65.8) 400 (67.0) 331 (65.8) 4: severe 233 (34.0) 196 (32.8) 171 (34.0) dlqi total, mean ± sd 10.5 ± 6.3 10.7 ± 6.3 10.9 ± 6.4 any prior systemic therapy, n (%) 547 (79.9) 486 (81.4) 415 (82.5) prior biologic therapy,b n (%) 275 (40.1) 245 (41.0) 210 (41.7) anti-tnf 96 (14.0) 86 (14.4) 74 (14.7) anti-il-17 171 (25.0) 150 (25.1) 126 (25.0) anti-il-23 34 (5.0) 33 (5.5) 29 (5.8) anti-il-12/23 37 (5.4) 32 (5.4) 28 (5.6) bkz 320 mg q4w (n=1456) eair/100 py (95% ci) bkz 320 mg q8w (n=930) eair/100 py (95% ci) bkz total (n=1495) eair/100 py (95% ci) any teae 219.6 (207.3, 232.3) 141.4 (129.6,153.9) 192.7 (182.5, 203.3) serious teaes 6.2 (5.1, 7.4) 5.3 (3.8, 7.0) 5.9 (5.0, 6.9) teaes leading to discontinuation 3.6 (2.8, 4.5) 2.7 (1.8, 4.1) 3.3 (2.7, 4.1) treatmentrelated teaes 43.4 (39.8, 47.1) 28.9 (25.0, 33.2) 35.5 (32.8, 38.3) severe teaes 5.3 (4.3, 6.5) 4.8 (3.4, 6.5) 5.0 (4.2, 5.9) teaes leading to death 0.3 (0.1, 0.7) 0.3 (0.1, 1.0) 0.3 (0.2, 0.6) most common teaesa nasopharyngitis 21.7 (19.4, 24.2) 17.2 (14.3, 20.4) 19.3 (17.5, 21.2) oral candidiasis 16.4 (14.5, 18.5) 9.6 (7.6, 12.0) 12.9 (11.5, 14.4) upper respiratory tract infection 9.1 (7.8, 10.7) 8.3 (6.5, 10.5) 8.4 (7.3, 9.6) among all bkz-treated patients over two years, the most frequent adverse events were nasopharyngitis, oral candidiasis, and upper respiratory tract infection, consistent with results through one year. aamong week 16 iga 0/1 responders; bamong week 16 bsa ≤1% responders; camong week 16 pasi 100 responders. athe be ready and be sure feeder studies ran for 56 weeks, while be vivid ran for 52 weeks; to pool the data across all 3 studies, week 56 data from the feeder studies were not included. maintenance of iga 0/1 maintenance of bsa ≤1% maintenance of pasi 100 week 16 week 16 week 16 ole week 48a ole week 48b ole week 48c 87.5% 93.9% 74.9% 90.7% 62.7% 83.7% 97.8% 92.5% 86.3% bkz 320 mg q4w (n=989) bkz 320 mg q4w (n=989) bkz 320 mg q4w (n=989) bkz 320 mg q4w/q4w/q4w (n=384) bkz 320 mg q4w/q8w/q8w (n=185) bkz 320 mg q4w/q4w/q4w (n=275) bkz 320 mg q4w/q8w/q8w (n=147) bkz 320 mg q4w/q4w/q4w (n=330) bkz 320 mg q4w/q8w/q8w (n=172) initial treatment period maintenance treatment perioda open-label extension period be bright (open-label extension) be sure, be vivid & be ready (pooled, double-blind) week 16 responders who entered the ole: q4w/q4w/q4w iga 0/1: n=384 bsa ≤1%: n=330 pasi 100: n=275 q4w/q8w/q8w iga 0/1: n=185 bsa ≤1%: n=172 pasi 100: n=147 week 52week 16week 0 week 80b (ole week 24) week 100b (ole week 48) bkz 320 mg q4w n=989 bkz 320 mg q4w bkz 320 mg q8w bkz 320 mg q4w bkz 320 mg q8w bkz 320 mg q4w bkz 320 mg q8w <pasi 90 ≥pasi 90 <pasi 90 ≥pasi 90 ≥pasi 90 ≥pasi 90 investigator discretion investigator discretion 1:4 weeks p ro p o rt io n o f p a ti e n ts a c h ie v in g i g a 0 /1 ( % ) 75 50 25 100 0 16 96 100886056a48402420 928476 807264 6852a28 32 36 44 double-blinded treatment open-label extension bkz 320 mg q4w/q4w/q4w (n=384) oc mnri nri 95.5% 93.9% 88.8% p ro p o rt io n o f p a ti e n ts a c h ie v in g i g a 0 /1 ( % ) 75 50 25 100 0 16 96 100886056a48402420 928476 807264 6852a28 32 36 44 double-blinded treatment open-label extension bkz 320 mg q4w/q8w/q8w (n=185) oc mnri nri 98.2% 97.8% 90.8% weeks p ro p o rt io n o f p a ti e n ts a c h ie v in g b s a ≤ 1 % ( % ) 75 50 25 100 0 16 96 100886056a48402420 928476 807264 6852a28 32 36 44 double-blinded treatment open-label extension bkz 320 mg q4w/q4w/q4w (n=330) oc mnri nri 92.5% 90.7% 85.8% p ro p o rt io n o f p a ti e n ts a c h ie v in g b s a ≤ 1 % ( % ) 75 50 25 100 0 16 96 100886056a48402420 928476 807264 6852a28 32 36 44 double-blinded treatment open-label extension bkz 320 mg q4w/q8w/q8w (n=172) oc mnri nri 94.3% 92.5% 86.6% weeks p ro p o rt io n o f p a ti e n ts a c h ie v in g p a s i 10 0 ( % ) 75 50 25 100 0 16 96 100886056a48402420 928476 807264 6852a28 32 36 44 double-blinded treatment open-label extension bkz 320 mg q4w/q4w/q4w (n=275) oc mnri nri 87.5% 83.7% 81.8% p ro p o rt io n o f p a ti e n ts a c h ie v in g p a s i 10 0 ( % ) 75 50 25 100 0 16 96 100886056a48402420 928476 807264 6852a28 32 36 44 double-blinded treatment open-label extension bkz 320 mg q4w/q8w/q8w (n=147) oc mnri nri 91.2% 86.3% 84.4% synopsis z seborrheic keratoses (sks) are among the most common benign cutaneous lesions, affecting approximately 84 million individuals in the united states.1 removal of sks by dermatologists often requires invasive cryosurgery, shave excision, electrosurgery, curettage, or laseror light-based treatment2; an unmet treatment need exists for the safe, noninvasive, and effective removal of sks3 z key reasons that individuals with sks prefer to have them treated or removed include concern with the seriousness of the lesion, physical irritation or pruritus, embarrassment from the visual appearance of the lesion, or the desire to look younger4 z eskata (hydrogen peroxide topical solution, 40% [w/w]; hp40; aclaris therapeutics, inc., wayne, pa) is a proprietary, stabilized, noninvasive treatment with demonstrated safety and efficacy in the removal of sks of the face, trunk, and extremities, and low risk of skin pigmentation changes or scarring3,5,6 — hp40 is the first us food and drug administration (fda)-approved topical treatment for individuals with raised sks3,6 objective z to describe segments of consumers with raised facial sks, identify specific concerns regarding treatment to remove sks and gain an understanding of barriers to treatment for facial/hairline sks methods study design z an online survey was conducted between september 28 and october 13, 2017 among 702 eligible participants aged 35–65 years — the sponsor was not identified to survey participants inclusion criteria z eligible participants were diagnosed with sks by a health care provider (hcp) or self-confirmed the presence of sks using the definition and example images provided for the survey z in addition, participants were required to meet the following criteria — bothered by appearance of sks located on the face or hairline (score ≥3 on a 5-point likert scale [1 = not at all bothered; 2 = slightly bothered; 3 = somewhat bothered; 4 = moderately bothered; 5 = extremely bothered]) — at least somewhat interested in an fda-approved topical treatment to remove sks on the face or hairline — annual income ≥$75,000 and residing in an urban or suburban area exclusion criteria z survey participant or immediate family member was an employee or consultant for any pharmaceutical, advertising, marketing, market research, or public relations company at the time of survey completion sample recruitment quotas z the sample population was estimated to include 140 males (20%) and 560 females (80%); ≥210 subjects (30%) had visited a dermatologist in the past 2 years z the estimated population by age was categorized as 35–39 years (10%), 40–49 years (40%), 50–59 years (40%), and 60–65 years (10%) z the population recruited for the survey was selected to mirror us census demographics for race and ethnicity z ≥210 subjects (30%) must have been to a dermatologist in the past 2 years survey questions z a summary of survey questions is provided in table 1 table 1. number of survey questions included by categorya 1. screening 17 questions 2. demographics and media habits 4 questions 3. lifestyle, personality, skin care attitudes and behaviors, and relationship with a dermatologist 24 questions 4. experience with sks 26 questions 5. profile of a product for treatment of sks 14 questions sks, seborrheic keratoses. athe inclusion of some questions was conditional based on previous participant responses. statistics z categorical data were presented as frequency and percentage; continuous variables were presented as mean (standard deviation [sd]) results demographics z a total of 702 survey participants were enrolled and were consistent with the sample recruitment quotas (table 2) table 2. demographics and characteristics of survey participants male 142 (20) age category 35–39 70 (10) 40–49 281 (40) 50–59 281 (40) 60–65 70 (10) visited dermatologist in previous 2 years 290 (41) mean (sd) household income, us dollars 120,566 (24,252) residing in a suburban area 547 (78) values are n (%) unless indicated otherwise. z the racial and ethnic demographics of enrolled survey participants are summarized in figure 1 figure 1. racial and ethnic background of population samplea black, afro-caribbean, african american 10% (n=69) non-hispanic white or euro-american 62% (n=436) hispanic/latin american 12% (n=81) east asian/asian american 13% (n=91) south asian/indian american 1% (n=6) multi-ethnic/racial 3% (n=19) athe sum of the percentages is greater than 100% due to rounding. z survey participants reported a fitzpatrick skin type of i or ii (33%), iii (42%), iv (16%), and v or vi (9%) z among survey participants who had visited a dermatologist, the most common reasons for doing so were routine skin cancer check (66%); removal of noncancerous skin growths, marks, or spots (52%); and to have a suspicious mole or spot checked (47%) z a total of 39% of participants reported that they were previously diagnosed with sks by an hcp — a total of 99% of participants confirmed the presence of spots, growths, or marks similar to the sks in the images provided concerns about sks z among the 468 participants (67%) with sks on multiple body locations, sks on the face or hairline were of greatest concern (86%) z a total of 314 participants (45%) had consulted a professional (eg, hcp, aesthetician) about the sks on their face or hairline; when asked why, among 208 responders the most common reasons given were concern that the lesion could be cancerous (60%) and dislike of how the spots looked or felt (56%) (figure 2) figure 2. question: why did you first ask about your facial sks?a 2 6 10 11 14 20 29 56 60 0 10 20 30 40 50 60 70 other friend or family member didn't like the way it looked/felt friend/family member concerned it could be cancer made me look like i didn't take care of myself made me look unhealthy irritated or itchy and were bothering me made me look older i didn't like the way it looked/felt concerned it was skin cancer survey responders (n=208), % sks, seborrheic keratoses. aparticipants could choose more than one response. coping strategies for sks z a majority of survey participants (n=591; 84%) reported attempts to mask or modify their sks — makeup application was the most common strategy (53%; 65% of females and 8% of males), followed by use of over-the-counter products, such as wart removers or antiaging products (44%), and avoidance of sun exposure (27%) (figure 3) figure 3. question: which of the following things have you ever done to hide, disguise, or deal with the sks on your face or hairline?a 16 4 6 6 13 13 15 27 44 53 28 3 8 7 20 9 23 25 28 8 13 4 5 6 11 14 17 27 48 65 0 10 20 30 40 50 60 70 never done any of these other wear clothing designed to hide hide with eyeglasses avoid looking at or touching them wear hair in a certain style to cover pick at them and let them fall o� stay out of the sun use otc products (eg, anti-aging moisturizers) use make-up to cover up survey participants, % female (n=560) male (n=142) all (n=702) otc, over-the-counter; sks, seborrheic keratoses. aparticipants could choose more than one response. z a majority of survey participants (n=569; 81%) were extremely interested or very interested in receiving treatment for their face/hairline sks (mean [sd] score = 4.3 [0.8]; figure 4) figure 4. question: suppose that there was a new fda-approved topical treatment to remove sks on the face and hairline. the treatment would be applied in the dermatologist’s office, but your insurance considers this a cosmetic treatment and you’d have to pay for the treatment on your own. assuming the cost of treatment was reasonable to you, how interested would you be in getting this treatment to remove the sks on your face/hairline? (n=702) 0 4 15 33 48 0 10 20 30 40 50 1 not at all interested 2 slightly interested 3 somewhat interested 4 very interested 5 extremely interested su rv ey p ar ti ci p an ts , % n=28 n=105 n=229 n=340 sks, seborrheic keratoses. z despite expressing high levels of interest in treatment, the majority of survey participants (n=502; 72%) elected not to have their facial or hairline sks removed (figure 5) z a total of 112 participants (24%) who had sks on the rest of the body had had them removed or treated figure 5. question: earlier you said you had not had any of the sks on your face or hairline removed or treated. please indicate if the factors presented here were a major reason you have not had them treated or removed.a 3 7 10 11 14 14 19 20 21 23 29 38 46 0 5 10 15 20 25 30 35 40 45 50 couldn't get an appointment with a dermatologist told need to return for multiple treatments removing sks would resolve only one of many other skin concerns wanted to avoid pain or discomfort of procedure it is easy to cover sks up didn't know where to go to have them removed the hcp did not o�er treatment appearance of sks do not bother enough didn't want to risk getting a scar learned there was not a medical reason wasn't aware of any treatment options or that they could be removed out-of-pocket costs too high there are other priorities in my life survey responders (n=502), % sks, seborrheic keratoses. aparticipants could choose more than one response. references 1. bickers dr, et al. j am acad dermatol. 2006;55:490-500. 2. jackson jm, et al. j drugs dermatol. 2015;14:1119-25. 3. baumann ls, et al. j am acad dermatol. 2018 jun 1 [epub ahead of print]. 4. del rosso jq. j clin aesthet dermatol. 2017;10:16-25. 5. dubois jc, et al. dermatol surg. 2018;44:330-40. 6. eskata [package insert]. wayne, pa: aclaris therapeutics, inc.; 2017. acknowledgments this study was sponsored by aclaris therapeutics, inc., wayne, pa. medical writing support was provided by peloton advantage, parsippany, nj, and funded by aclaris therapeutics, inc. disclosures shuai xu, md, msc, reports consulting for aclaris therapeutics. he also reports grant support from pfizer inc, leo pharma, and novartis. stacy wang, pharmd, is an employee of aclaris therapeutics, inc., and esther estes, md, mph, is a former employee of aclaris therapeutics, inc. email address for questions or comments: stevexumd@gmail.com conclusions 1 individuals with sks on the face or hairline have concerns about potential skin cancer and/or appearance 2 over two-thirds of patients reported interest in removal of sks but did not have them removed; reasons cited included lack of awareness that removal treatment options exist (29%) and never being offered the option by their hcps (19%) 3 findings from this survey highlight the negative impact that benign sks could have on patients. in addition, the findings inform dermatologists and other hcps on missed opportunities to improve communications with patients on sk treatment options the hidden impact of seborrheic keratoses: analysis of a psychometric survey of an ethnically diverse cohort of u.s. adults shuai xu, md, msc,1 stacy wang, pharmd,2 esther estes, md, mph3 1northwestern university feinberg school of medicine, chicago, il; 2aclaris therapeutics, inc., wayne, pa; 3formerly of aclaris therapeutics, inc., wayne, pa presented at the fall clinical dermatology conference, october 18–21, 2018, las vegas, nevada powerpoint presentation presented at 2021 fall clinical dermatology conference, las vegas, nv, usa, october 21–24, 2021 introduction • seborrheic dermatitis (seb derm) is a chronic inflammatory skin condition that causes physical discomfort and emotional burden for patients1,2 – seb derm is characterized by erythematous, scaly plaques, with a yellowish, oily, moist, and/or greasy appearance and affects areas with abundant sebaceous glands3,4 – seb derm can negatively impact quality of life, particularly in patients with more severe disease5 • topical treatments include antifungals, steroids, immunomodulators, and dandruff shampoos,3,4 but efficacious and safe options are needed, especially for long-term use • roflumilast is a selective and highly potent phosphodiesterase-4 inhibitor being investigated for once-daily, nonsteroidal, treatment of several dermatologic conditions,6 including seb derm • a phase 2, 8-week study investigating roflumilast foam 0.3% once-daily for the treatment of seb derm (clinicaltrials.gov identifier: nct04091646) was recently completed methods • this was a phase 2a, parallel-group, double-blind, vehicle-controlled, 8-week clinical trial of once-daily roflumilast foam 0.3% for the treatment of seb derm • eligible patients were adults (≥18 years) with a clinical diagnosis of seb derm of at least 3 months’ duration, an investigator global assessment (iga) score ≥3 (moderate severity), and affecting ≤20% of the body surface area (bsa), including the scalp, face, trunk, and/or intertriginous areas (figure 1) • patients were randomized in a 2:1 ratio to roflumilast foam 0.3% or vehicle foam, which was applied once daily to lesions of seb derm • the intention-to-treat (itt) population included all randomized patients, while the modified intent-to-treat (mitt) population included all randomized patients with the exception of 2 patients who missed the week 8 iga assessment due to the covid-19 disruption – the primary efficacy analysis was based on the mitt population and repeated for the itt population • the primary efficacy endpoint was analyzed using a cochran-mantel-haenszel test stratified by study site and baseline disease severity; statistical significance was concluded at the 10% significance level (2-sided) – missing iga scores were imputed using multiple imputation a randomized, double-blind, vehicle-controlled phase 2a study evaluating once daily roflumilast foam 0.3% in patients with moderate to severe seborrheic dermatitis results • a total of 226 patients were randomized to roflumilast foam (n=154) or vehicle foam (n=72; figure 2) – one roflumilast-treated patient and one vehicle-treated patient withdrew or missed the week 8 evaluation due to covid-19 disruption (table 1) • overall, 92% of patients completed the study (table 2) – few patients discontinued due to adverse events (aes) • demographics and baseline characteristics were similar in the treatment groups (table 3) conclusions • roflumilast foam 0.3% demonstrated significant improvement in iga success, erythema, scaling, and itch – the improvements in iga success were statistically significant at the first post-baseline visit (week 2) and continued through week 8 – roflumilast foam resulted in significant improvements in itch by week 2 • ~80% of patients reported notable itch at baseline (wi-nrs ≥4) – roflumilast reduced bsa affected and improved patient quality of life (dlqi) • rates of treatment-related aes, discontinuations due to aes, and application-site pain were low and similar to vehicle • in this phase 2a study, investigational, once-daily roflumilast foam 0.3% was demonstrated to be a safe, welltolerated, and effective treatment of seb derm with early onset of action and warrants further investigation as a potentially novel treatment matthew zirwas,1 zoe d. draelos,2 janet dubois,3 leon h. kircik,4 angela y. moore,5 linda stein gold,6 javier alonso-llamazares,7 michael bukhalo,8 suzanne bruce,9 kimmie eads,10 lawrence j. green,11 scott t. guenthner,12 laura k. ferris,13 seth forman,14 steven e. kempers,15 edward lain,16 charles w. lynde,17 david m. pariser,18 darryl p. toth,19 paul s. yamauchi,20 amy feng21, robert c. higham,21 patrick burnett,21 david r. berk21 1dermatologists of the central states, probity medical research, and ohio university, bexley, oh, usa; 2dermatology consulting services, high point, nc, usa; 3dermresearch, inc., austin, tx, usa; 4icahn school of medicine at mount sinai, ny, indiana medical center, indianapolis, in, physicians skin care, pllc, louisville, ky, and skin sciences, pllc, louisville, ky, usa; 5arlington center for dermatology, arlington research center, arlington, tx, and baylor university medical center, dallas, tx, usa; 6henry ford medical center, detroit, mi, usa; 7driven research llc, coral gables, fl, usa; 8arlington dermatology, rolling meadows, il, usa; 9sba dermatology, houston, tx, usa; 10the indiana clinical trials center, pc, plainfield, in, usa; 11george washington university school of medicine, rockville, md, usa; 12the dermatology center of indiana, pc, plainfield, in, and the indiana clinical trials center, pc, plainfield, in, usa; 13university of pittsburgh, department of dermatology, pittsburgh, pa, usa; 14forcare medical center, tampa, fl, usa; 15minnesota clinical study center, fridley, mn, usa; 16sanova dermatology, austin, tx, usa; 17university of toronto, toronto, lynde centre for dermatology, markham, and probity medical research, markham, on, canada; 18eastern virginia medical school and virginia clinical research, inc., norfolk, va, usa; 19xlr8 medical research, probity medical research, windsor, on, canada; 20david geffen school of medicine at ucla, los angeles, and dermatology institute & skin care center, inc., santa monica, ca, usa; 21arcutis biotherapeutics, inc., westlake village, ca, usa references 1. araya m, et al. indian j dermatol 2015;60:519. 2. pärna e, et al. acta derm venereol 2015; 95:312-316. 3. clark gw, et al. am fam physician 2015;91:185-190. 4. kastarinen h, et al. cochrane database syst rev 2014:cd009446. 5. peyrí j, et al. actas dermosifiliogr 2007;98:476-482. 6. lebwohl mg, et al. n engl j med 2020;383:229-239. acknowledgements • this study was supported by arcutis biotherapeutics, inc. • thank you to the investigators and their staff for their participation in the trial • we are grateful to the study participants and their families for their time and commitment • writing support was provided by christina mcmanus, phd, alligent biopharm consulting llc, and funded by arcutis biotherapeutics, inc. safety • rates of aes were low (table 4) • few treatment-related aes were reported • very few aes led to study discontinuation – rates of discontinuation were similar between roflumilast and vehicle groups • no patients had a serious ae • ≥99% of roflumilast-treated and ≥98% of vehicle-treated patients had no evidence of irritation on the investigatorrating of local tolerability table 2. patient disposition patients, n (%) roflumilast foam 0.3% (n=154) vehicle (n=72) overall (n=226) completed 141 (91.6) 67 (93.1) 208 (92.0) prematurely discontinued 13 (8.4) 5 (6.9) 18 (8.0) reason for discontinuation withdrawal by patient 4 (2.6) 1 (1.4) 5 (2.2) protocol violation 0 1 (1.4) 1 (0.4) lost to follow-up 6 (3.9) 2 (2.8) 8 (3.5) adverse event 2 (1.3) 1 (1.4) 3 (1.3) other 1 (0.6) 0 1 (0.4) efficacy • roflumilast foam 0.3% demonstrated significant and rapid improvement in seb derm as indicated by the percentage of patients achieving iga success (figure 2) – a significant benefit was observed by week 2 (the first timepoint evaluated) • roflumilast foam 0.3% significantly improved both redness (erythema success) and scaling (scaling success) associated with seb derm (figure 3) • roflumilast foam 0.3% resulted in significant and rapid improvement in itch as indicated by improvements on the wi-nrs (figure 4) • roflumilast foam 0.3% provided treatment benefit by reducing bsa affected and improving dermatology life quality index (dlqi; figure 5) iga success = clear or almost clear plus ≥2-grade improvement from baseline. bsa: body surface area; dlqi: dermatology life quality index; iga: investigator global assessment; qd: once daily; wi-nrs: worst itch-numeric rating scale. figure 1. study design endpoints primary • iga success at week 8 secondary • erythema • scaling • wi-nrs • bsa • dlqi safety and tolerability 8 weeks dosing eligibility • diagnosis of at least moderate seborrheic dermatitis (iga ≥3) • age 18+ • <20% bsa roflumilast foam 0.3% qd (n=154) vehicle qd (n=72) ra nd om iz e 2:1 n=226 table 3. demographics (safety population) roflumilast foam 0.3% (n=154) vehicle (n=72) overall (n=226) age in years, mean 45.3 44.2 44.9 gender, n (%) male 76 (49.4) 40 (55.6) 116 (51.3) female 78 (50.6) 32 (44.4) 110 (48.7) ethnicity, n (%) hispanic or latino 29 (18.8) 16 (22.2) 45 (19.9) not hispanic or latino 125 (81.2) 56 (77.8) 181 (80.1) race, n (%) american indian or alaskan native 1 (0.6) 0 1 (0.4) asian 7 (4.5) 1 (1.4) 8 (3.5) black or african american 17 (11.0) 6 (8.3) 23 (10.2) native hawaiian or other pacific islander 0 0 0 white 123 (79.9) 62 (86.1) 185 (81.9) other 1 (0.6) 2 (2.8) 3 (1.3) more than one race 5 (3.2) 1 (1.4) 6 (2.7) bsa, mean % 3.3 3.0 3.2 baseline iga (0–4), n (%) 3 – moderate 141 (91.6) 69 (95.8) 210 (92.9) 4 – severe 13 (8.4) 3 (4.2) 16 (7.1) baseline erythema (0–3), n (%) 2 – moderate 135 (87.7) 66 (91.7) 201 (88.9) 3 – severe 19 (12.3) 6 (8.3) 25 (11.1) baseline scaling (0–3), n (%) 2 – moderate 130 (84.4) 58 (80.6) 188 (83.2) 3 – severe 24 (15.6) 14 (19.4) 38 (16.8) wi-nrs mean 5.8 5.7 5.8 median 6.0 6.0 6.0 ≥4, n (%) 125 (81.2) 59 (81.9) 184 (81.4) facial involvement, n (%) 100 (64.9) 36 (50.0) 136 (60.2) safety population: all patients who were enrolled and received at least 1 confirmed dose of investigational product. bsa: body surface area; iga: investigator global assessment; wi-nrs: worst itch-numeric rating scale.table 1. study populations patients, n (%) roflumilast foam 0.3% vehicle overall itt 154 (100) 72 (100) 226 (100) safety population 154 (100) 72 (100) 226 (100) mitta 153 (99.4) 71 (98.6) 224 (99.1) pru4 125 (81.2) 59 (81.9) 184 (81.4) aexcludes 2 patients: one roflumilast-treated patient (31003) who was enrolled march 6, then withdrew consent due to the fear of contracting covid-19 (informed site may 1), with no post-baseline visits, and 1 vehicle-treated patient (17006) who missed week 8 iga due to covid, but did not discontinue due to covid, and came back for the week 9 visit. itt: intent-to-treat, all randomized patients. safety population: all patients who were enrolled and received at least 1 confirmed dose of investigational product. mitt: modified intent-to-treat, all randomized patients except those who missed the week 8 an investigator global assessment (iga) assessment specifically due to covid-19 disruption. pru4 population: subset of itt, includes patients with worst itch-numeric rating scale pruritus score ≥4 at baseline. table 4. adverse events n (%) roflumilast foam 0.3% (n=154) vehicle foam (n=72) patients with any teae 37 (24.0) 13 (18.1) patients with any treatment-related teae 3 (1.9) 3 (4.2) patients with any serious ae 0 0 patients who discontinued study due to aea 2 (1.3) 2 (2.8) most common teae (>2% in any group), preferred term contact dermatitisb 3 (1.9) 2 (2.8) insomnia 3 (1.9) 1 (1.4) nasopharyngitis 3 (1.9) 0 aaes leading to discontinuation for roflumilast were application-site pain (1 patient), migraine, dyspnea (both reported in the same patient). in the vehicle group: application-site dysesthesia. ball cases of contact dermatitis were reported to be unrelated to treatment and did not require a change in dosing of study intervention; 2 cases were reported as poison ivy rash. data are presented for safety population (all patients who were enrolled and received at least 1 confirmed dose of investigational product). ae: adverse event; teae: treatment-emergent adverse event. disclosures mz, jd, lk, am, lsg, ja-l, mb, sb, ke, ljg, stg, lkf, sf, sek, el, cwl, dmp, dpt, and psy are investigators and/or consultants for arcutis biotherapeutics, inc. and received grants/research funding and/or honoraria; af, rch, pb, and drb are employees of arcutis biotherapeutics, inc. additional disclosures provided on request. ci: confidence interval; iga: investigator global assessment; mitt: modified intent-to-treat, all randomized patients except those who missed the week 8 iga assessment specifically due to covid-19 disruption. figure 2. percentages of patients achieving iga success at each visit (mitt) bsa: body surface area; cfb: change from baseline; dlqi: dermatology life quality index; ls: least squares; se: standard error. erythema success defined as erythema score of none (0) or mild (1) plus ≥2-grade improvement from baseline; scaling success defined as scaling score of none (0) or mild (1) plus ≥2-grade improvement from baseline. ci: confidence interval; mitt: modified intent-to-treat, all randomized patients except those who missed the week 8 investigator global assessment specifically due to covid-19 disruption. figure 3. patients achieving erythema success (a) and scaling success (b) at each visit (mitt) figure 4. patients achieving wi-nrs success at each visit -100 -90 -80 -70 -60 -50 -40 -30 -20 -10 0 week 8 ch an ge f ro m b as el in e (% ) in b sa a ff ec te d (s e) roflumilast 0.3% (n=153) vehicle (n=71) -66.6% -28.5% significant improvements in bsa affected and dlqi at week 8 (a) (b) 1-4 -3.5 -3 -2.5 -2 -1.5 -1 -0.5 0 baseline week 2 week 4 week 8 ls m ea n cf b in d lq i ( se ) roflumilast 0.3% (n=153) vehicle (n=71) p=0.0380 p=0.0218 wi-nrs success defined as achievement of a ≥4-point improvement from baseline score of ≥4. ci: confidence interval; wi-nrs: worst itch-numeric rating scale. 43% of patients achieved an erythema score of 0 at week 8 22.5% 35.7% 44.7% 5.9% 10.4% 21.2% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% week 2 week 4 week 8 pa ti en ts (% ) roflumilast 0.3% (n=153) vehicle (=71) p=0.0065 p=0.0002 p=0.0021 erythema success 100 90 80 70 60 50 40 30 20 10 0 % o f p at ie nt s (9 5% c i) (a) about 50% of patients achieved a scaling score of 0 at week 8 26.5% 41.3% 56.0% 14.7% 20.9% 27.3% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% week 2 week 4 week 8 pa ti en ts (% ) roflumilast 0.3% (n=153) vehicle (n=71) p=0.0122 p=0.0003 scaling success 100 90 80 70 60 50 40 30 20 10 0 % o f p at ie nt s (9 5% c i) (b) 33.8% 56.6% 73.8% 14.7% 28.4% 40.9% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% week 2 week 4 week 8 pa tie nt s (% ) roflumilast 0.3% (n=153) vehicle (n=71) p=0.0033 p<0.0001 iga success = clear or almost clear plus ≥2-grade improvement from baseline p=0.0002 primary endpoint 35.5% of roflumilast-treated patients achieved iga status of clear at week 8 vs 15.2% of vehicle-treated patients 100 90 80 70 60 50 40 30 20 10 0 % o f p at ie nt s (9 5% c i) 52.8% 58.3% 64.6% 23.2% 28.3% 34.0% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% week 2 week 4 week 8 pa tie nt s (% ) roflumilast 0.3% (n=125) vehicle (n=58) about 65% of patients achieved a wi-nrs 4-point response at week 8 100 90 80 70 60 50 40 30 20 10 0 p=0.0007 p=0.0009 p=0.0007 % o f p at ie nt s (9 5% c i) figure 5. bsa affected (a) and dlqi (b) 0 ‒0.5 ‒1 ‒1.5 ‒2.5 ‒3.5 ls m ea n cf b in d lq i ( se ) ‒4 ‒3 ‒2 0 ‒20 ‒40 ‒60 cf b (% ) i n bs a a ff ec te d (s e) ‒100 ‒80 a randomized, double-blind, 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true >> ] >> setdistillerparams << /hwresolution [2400 2400] /pagesize [612.000 792.000] >> setpagedevice screening washout of tcs and other ad medication initial treatment maintenance treatment safety follow-up o -treatment period 3:1 randomization tralokinumab 300 mg q2w placebo tralokinumab 300 mg q2w tralokinumab 300 mg q4w placebo placebo open-label tralokinumab 300 mg q2w + optional tcsopen-label tralokinumab 300 mg q2w + optional tcs ecztra 1 japanecztra 1 japan responders (2:2:1) ecztra 1 and ecztra 2 non-responders patients transferred from maintenance treatment if specific criteria are met placebo placebo 2:1 randomization tralokinumab 300 mg q2w tralokinumab 300 mg q2w tralokinumab 300 mg q2w tralokinumab 300 mg q4w tcs ecztra 3 responders (1:1) non-responders non-responders responders tralokinumab 300 mg q2w 1:1:1:1 randomization tralokinumab 300 mg q2w tralokinumab 150 mg q2w tralokinumab 45 mg q2w placebo tcs phase 2b dose-finding trial tcs 1:1 randomization tralokinumab 300 mg q2w placebo ecztra 5 + vaccines + vaccines figure 1. study design duration of first event, days tralokinumab (n=1605) placebo (n=680) n 100 17 median (iqr) 21.0 (11.0–88.0) 14.0 (5.0–29.0) table 4. duration of the first event of conjunctivitis aesisa (safety analysis set, ad pool, initial treatment period)introduction objective ● the objective of this study was to report an overview of the conjunctivitis data in adult patients with moderate-to-severe ad pooled from the three phase 3 ecztra trials and the two phase 2 trials of tralokinumab 300 mg every 2 weeks (q2w) versus placebo tralokinumab total (n=1605) placebo total (n=680) hr vs placebo (95% ci) ae pye n (%) adj. % r adj. r pye n (%) adj. % r adj. r conjunctivitis 453.7 126 (7.9) 7.5 27.8 26.6 190.3 21 (3.1) 3.2 11.0 11.4 2.4 (1.5, 3.8) conjunctivitis 459.6 90 (5.6) 5.4 19.6 19.0 191.4 13 (1.9) 1.9 6.8 7.0 2.8 (1.6, 5.0) conjunctivitis allergic 467.9 34 (2.1) 2.0 7.3 6.7 191.9 7 (1.0) 1.1 3.6 3.8 1.8 (0.8, 4.0) conjunctivitis bacterial 472.6 4 (0.2) 0.2 0.8 0.7 192.8 1 (0.1) 0.2 0.5 0.6 1.3 (0.2, 12.0) conjunctivitis viral 473.0 1 (0.1) 0.1 0.2 0.2 193.1 1 (0.1) 0.1 0.5 0.5 0.4 (0.0, 6.5) table 1. summary of conjunctivitis aesis by preferred term (first event only, ad pool, initial treatment period) with conjunctivitis aesis without conjunctivitis aesis characteristic all treated (n=147) tralokinumab (n=126) placebo (n=21) all treated (n=2138) tralokinumab (n=1479) placebo (n=659) median baseline easi (iqr) 32.0 (21.8–42.6) 30.8 (21.8–41.5) 33.5 (25.6–43.0) 26.7 (19.8–38.9) 26.8 (19.8–38.6) 26.6 (19.7–39.7) baseline iga, n (%) iga-3, moderate 57 (38.8) 51 (40.5) 6 (28.6) 1145 (53.6) 789 (53.3) 356 (54.0) iga-4, severe 90 (61.2) 75 (59.4) 15 (71.4) 990 (46.3) 687 (46.5) 303 (46.0) iga-5, very severe – – – 3 (0.1) 3 (0.2) – allergic conjunctivitis, n/n (%)a never 62/145 (42.8) 57/126 (45.2) 5/19 (26.3) 1363/2037 (66.9) 969/1427 (67.9) 394/610 (64.6) current 60/145 (41.4) 48/126 (38.1) 12/19 (63.2) 387/2037 (19.0) 261/1427 (18.3) 126/610 (20.7) past 22/145 (15.2) 20/126 (15.9) 2/19 (10.5) 227/2037 (11.1) 151/1427 (10.6) 76/610 (12.5) table 3. summary of easi and iga scores at baseline and atopic comorbidities in patients with and without conjunctivitis aesis (safety analysis set, ad pool, initial treatment period) conclusions ● the overall incidence of conjunctivitis, identified as an aesi in the initial treatment period for the pooled data set of 2285 patients from the five phase 2/phase 3 clinical trials, was higher for tralokinumab 300 mg q2w than for placebo ● the majority of the first events of conjunctivitis were mild to moderate in severity ● most of the patients who experienced a conjunctivitis event received treatment and their conjunctivitis resolved or was resolving during the trial period ● patients with conjunctivitis were found to have more severe ad at baseline and had a history of allergic conjunctivitis, which may be predisposing factors to conjunctivitis in ad patients conjunctivitis in tralokinumab-treated adult patients with moderate-to-severe atopic dermatitis: pooled results from five clinical trials andreas wollenberg,1 lisa a beck,2 marjolein de bruin weller,3 rebecca zachariae,4 christina kurre olsen,4 jacob p thyssen5 1klinikum der universität münchen, klinik und poliklinik für dermatologie und allergologie, munich, germany; 2department of dermatology, medicine and pathology, university of rochester medical center, rochester, ny, usa; 3department of dermatology and allergology, university medical center utrecht, utrecht, the netherlands; 4leo pharma a/s, ballerup, denmark; 5department of dermatology and allergy, herlev and gentofte hospital, university of copenhagen, hellerup, denmark ● atopic dermatitis (ad) is a chronic inflammatory skin disease1,2 characterised by eczematous lesions and multiple symptoms, including pruritus, sleep disturbance and depression3-5 ● ocular comorbidities such as various forms of conjunctivitis are commonly present in patients with ad and the incidence of ocular complications is known to increase with ad severity6 ● increased rates of conjunctivitis have been reflected in clinical trials of moderate-tosevere patients with ad7, as well as in real-world data8 ● the type 2 cytokine interleukin 13 (il-13) has been identified as a key driver of the underlying inflammation of ad and is overexpressed in lesional and non-lesional ad skin9,10 ● tralokinumab is a fully human immunoglobulin g4 monoclonal antibody that specifically binds to the il-13 cytokine with high affinity, preventing interaction with the il-13 receptor and subsequent downstream il-13 signalling, thus preventing its pro-inflammatory activity11 – recent phase 3 trials have investigated tralokinumab in the treatment of moderate-to-severe ad versus placebo (ecztra 1 [nct03131648] and ecztra 2 [nct03160885]) and in combination with topical corticosteroids (tcs) versus placebo (ecztra 3 [nct03363854]) – phase 2 trials have assessed the efficacy and safety of tralokinumab in combination with tcs (phase 2b [nct02347176]), as well as of tralokinumab-treated patients’ responses to vaccines (ecztra 5 [nct03562377]) patients ● eligible patients were 18 years of age with a confirmed diagnosis of ad for 1 year and with an inadequate response to treatment with topical medications. additional eligibility requirements included an ad body surface area involvement of 10%, eczema area and severity index (easi) scores of 12 at screening and 16 at baseline (ecztra trials) or 12 at baseline (phase 2b trial) and an investigator’s global assessment (iga) score of 3 study designs ● phase 3 ecztra 1 and ecztra 2 (tralokinumab monotherapy), phase 3 ecztra 3 (tralokinumab in combination with tcs), phase 2 ecztra 5 (vaccine response in tralokinumab-treated patients with ad) and phase 2b (efficacy and safety evaluation of tralokinumab) trials (figure 1) winter clinical dermatology conference, january 16-24, 2021 ● the analyses evaluated all randomized patients (n=2285) who received at least one dose of tralokinumab 300 mg q2w (n=1605) or placebo (n=680), pooled from the five trials – results described below are based on the first conjunctivitis event incidence and severity of conjunctivitis ● the overall adjusted incidence and adjusted rate of conjunctivitis aesis were 7.5%/26.6 for tralokinumab and 3.2%/11.4 for placebo and the hr versus placebo was 2.4 (95% ci 1.5, 3.8) (table 1) – the majority of conjunctivitis aesis were reported as the preferred term ‘conjunctivitis’ ● most conjunctivitis aesis were mild to moderate in severity in both the tralokinumab and placebo arms (figure 2) ● conjunctivitis events (based on all conjunctivitis events) recovered/resolved (78.6% vs 73.9%) or were considered to be recovering/resolving (2.8% vs 4.3%) in the tralokinumab group and placebo group, respectively (table 2) – there were no serious events, although events led to permanent discontinuation of two (1.4%) tralokinumab patients ● of the 145 conjunctivitis aesis in the tralokinumab group, 39 (27.1%) were confirmed diagnoses. of the 21 conjunctivitis aesis in the placebo group, six (29%) were confirmed diagnoses (data available from the ecztra trials only) tralokinumab total e (%) placebo total e (%) events 145 23 drug relateda action taken with drug drug withdrawn 2 (1.4) – outcome fatal – – not recovered/not resolved 26 (17.9) 5 (21.7) recovering/resolving 4 (2.8) 1 (4.3) recovered/resolved 114 (78.6) 17 (73.9) recovered/resolved with sequelae 1 (0.7) – unknown – – table 2. overall summary of aesis – conjunctivitis (all events, ad pool, initial treatment period) arelated aes comprise aes considered possibly or probably related by the investigator and aes with missing causality. %, percentage calculated based on number of events divided by total number of events; e, number of aes. hr and 95% ci are from a cox regression model with treatment groups as fixed effect, stratified by trial and baseline disease severity (iga). %, percentage of patients with one or more events; adj. %, adjusted percentage calculated using cochran-mantel-haenszel weights; r, adjusted rate calculated using cochran-mantel-haenszel weights; n, number of patients; n, number of patients with one or more events; pye, patient-years of exposure calculated by preferred term until onset of the first event; r, rate (number of patients divided by pye multiplied by 100). apooled data only include the ecztra trials. iqr, interquartile range; n, number of patients; n, number of patients with observation. aincluding only events that have an end date. iqr, interquartile range. adjusted incidences are presented; percentages above the bars represent the adjusted incidence rate overall. figure 2. conjunctivitis severity in tralokinumab-treated and placebo-treated patients (first event only, ad pool, initial treatment period) 5.0 2.1 2.4 1.1 0.1 0.0 2.0 4.0 6.0 8.0 10.0 12.0 14.0 16.0 18.0 20.0 tralokinumab (n=1605) placebo (n=680) p a ti e n ts w it h c o n ju n ct iv it is , % mild moderate severe 7.5% 3.2% figure 3. time to onset of first conjunctivitis event (safety analysis set, ad pool, initial treatment period) time since first dose of trial product, weeks c u m u la ti ve in c id e n ce tralokinumab total (n=1605) placebo total (n=680) 0 4 8 12 16 0.35 0.30 0.25 0.20 0.15 0.10 0.05 0.00 aesis from the ecztra trials are presented based on aesi criteria being met, as evaluated by the investigator. aesis from the dosefinding trial are based on a specified meddra search. disease characteristics with and without conjunctivitis ● patients with conjunctivitis aes had slight but consistently increased severity in easi and iga scores at baseline (table 3) – in patients who reported conjunctivitis during the initial treatment period, median easi score at baseline was 32.0 and 61.2% had severe disease (iga-4), compared to a median easi score of 26.7 and 46.3% with iga-4 at baseline in patients who did not report conjunctivitis, regardless of treatment group ● patients with a history of allergic conjunctivitis were observed to have an increased incidence of conjunctivitis, as reported in the trial. in total, 56.6% of patients who reported conjunctivitis in the pooled data set, compared to 30.1% of patients who did not report conjunctivitis, had a history of allergic conjunctivitis onset and duration of conjunctivitis ● the events of conjunctivitis reported during the initial treatment period had onset throughout the initial treatment period in both treatment groups. the difference in mean number of conjunctivitis events between the treatment groups became apparent from week 4 and increased over time (figure 3) ● the median time to first event was similar for both treatment groups (50.0 days vs 54.0 days) ● however, the duration of the first conjunctivitis event was longer in the tralokinumab group compared to the placebo group (21.0 days vs 14 days) (table 4) common treatments ● the majority of patients in both treatment groups received treatment for their conjunctivitis (85.7% of tralokinumab patients vs 71.4% of placebo patients) ● common treatments in tralokinumab-treated and placebo-treated patients included ophthalmic anti-allergics (31.0% vs 38.1%), anti-infectives (30.2% vs 19.0%), corticosteroids (23.0% vs 9.5%) and combined corticosteroids and anti-infectives (13.5% vs 14.3%) references 1. nutten s. ann nutr metab 2015; 66 (suppl 1): 8–16. 2. weidinger s, novak n. lancet 2016; 387: 1109–1122. 3. eckert l et al. j am acad dermatol 2017; 77: 274–279.e273. 4. silverberg ji et al. ann allergy asthma immunol 2018; 121: 340–347. 5. dalgard fj et al. j invest dermatol 2015; 135: 984–991. 6. thyssen jp et al. j am acad dermatol 2017; 77: 280–286.e281. 7. akinlade b et al. br j dermatol 2019; 181: 459–473. 8. faiz s. j am acad dermatol 2019; 81: 142-151. 9. bieber t. allergy 2020; 75: 54–62. 10. tsoi lc et al. j invest dermatol 2019; 139: 1480–1489. 11. popovic b et al. j mol biol 2017; 429: 208–219. disclosures andreas wollenberg has received grants, personal fees or non-financial support from abbvie, almirall, beiersdorf, bioderma, chugai, galapagos, galderma, hans karrer, leo pharma, lilly, l’oréal, maruho, medimmune, novartis, pfizer, pierre fabre, regeneron, santen and sanofi-aventis. lisa a beck has received consulting fees from regeneron. marjolein de bruin weller is a consultant/advisor for abbvie , eli lilly, pfizer, regeneron pharmaceuticals, sanofi genzyme, and ucb, and has received grant/research support from regeneron pharmaceuticals and sanofi genzyme. rebecca zachariae and christina kurre olsen are employees of leo pharma. the ecztra trials were sponsored by leo pharma results materials and methods adverse event (ae) reporting ● conjunctivitis was classified as an ae of special interest (aesi) and comprised the following preferred terms: ‘conjunctivitis’, ‘conjunctivitis allergic’, ‘conjunctivitis bacterial’ and ‘conjunctivitis viral’, and was summarized for the initial treatment period (16 weeks for ecztra and 12 weeks for phase 2b) ● events were captured from the ae form (ecztra) or from a medical dictionary for regulatory activities (meddra) search (phase 2b) statistical analysis ● results presented are based on the safety analysis set, which comprises all randomized patients who were exposed to investigational medicinal product ● cochran-mantel-haenszel weights were applied to calculate adjusted ae incidences to account for different randomization rates between tralokinumab and placebo ● rates were calculated using the number of patients divided by patient-years of exposure (pye) multiplied by 100 ● hazard ratio (hr) and 95% confidence interval (ci) are from a cox regression model with treatment groups as fixed effect, stratified by trial and baseline disease severity (iga) skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 462 in-depth review atopic dermatitis: preventing and managing the itch that rashes, and a case for the multi-theory model (mtm) for health behavior change for educational interventions kayla penny, m31, manoj sharma, mbbs, phd, mches® 2, amy e. flischel, md3, robert t. brodell, md3, vinayak k. nahar md, phd, ms3,4 1 lsu health shreveport school of medicine, shreveport, la 2 department of environmental & occupational health, school of public health, university of nevada, las vegas, nv 3 department of dermatology, school of medicine, university of mississippi medical center, jackson, ms 4 department of preventive medicine, school of medicine/john d. bower school of population health, university of mississippi medical center, jackson, ms atopic dermatitis atopic dermatitis (ad), or eczema, is the most common chronic noncontagious inflammatory skin condition in the world (1). it presents with chronic relapsing pruritic patches and plaques in a distinct distribution and is associated with other atopic conditions (asthma and allergic rhinitis). while the underlying etiology of atopic dermatitis is still not completely understood, it is thought to be multifactorial, involving genetic, psychosocial, and environmental factors, a defective skin barrier, and altered immunologic responses, whereby, predisposed individuals develop cutaneous hypersensitivity to environmental antigens. abstract atopic dermatitis (ad) is a multifactorial disease affected by a host of genetic, environmental, socioeconomic and demographic influences, that induce the atopic immune response in predisposed individuals. despite treatment with topical corticosteroids to reduce skin inflammation, emollients to improve the skin barrier, and avoidance of inflammatory triggers, many patients report progressive symptoms. management strategies are developed as modifiable environmental influences are identified. managing atopic dermatitis requires adaptive changes in health behavior involving the patient and often the caregiver. multi-theory models (mtm) have not yet been used in ad interventions but may prove beneficial as they use behavior concepts to predict both initiation and sustenance in education health interventions. a comprehensive approach fosters such changes by using psychological and educational strategies as adjuncts to conventional therapy. this article reviews the challenges in managing ad and the potential impact of behavioral theories. this is designed to strengthen the argument for using an mtm model in future studies of ad. skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 463 signs and symptoms of ad in children the diagnosis of ad is made primarily on clinical grounds. severe pruritus is a universal symptom and erythematous, scaly or lichenified, excoriated papules and plaques are commonly seen (2). these findings are distributed in age-specific patterns. babies present with a papulosquamous morphology on facial and extensor surfaces, which gravitates to flexor creases as patients age. the signs and symptoms are associated with the itchscratch cycle. pruritus leads to scratching that damages the integrity of the skin barrier producing inflammation that causes more pruritus. the absence of filaggrin, a key moisture-protective element in the stratum corneum, enables antigens associated with external pathogens to penetrate the skin exacerbating the allergic response. consequences of ad in children the distressing, chronic, waxing and waning course of ad severely impacts quality of life. chamlin et al. (2004) studied the impact of ad on children and their families. nearly 180 quality-of-life outcomes were identified and grouped by domains as related to physical health, emotional health, physical functioning, and social functioning (3). the effects on the child and the family were assessed in each domain. the physical health and physical functioning domains had the most deleterious effects on the child. pruritus and scratching can lead to pain, bleeding and sleep disturbance. other studies have demonstrated that sleep disturbances resulting from atopic dermatitis also carry a psychosocial burden reflected by drowsiness, inability to focus, irritability, and growth restriction (4). impacts on physical functioning include clothing restrictions, interference with indoor and outdoor activities such as bathing and swimming, and embarrassment (5). while the effects of physical health and functioning more directly impact the child suffering from ad, emotional influences often produce social effects that impact both children and families. for example, children with atopic dermatitis who display behavioral problems and irritability may interact less with other children (social impairment) (5). in addition, the emotional and social impacts on families may be worsened by the economic burden carried by families of children with ad. these annual expenditures can be categorized as: 1) direct costs including expenditures on prescription drugs, otc products, inpatient and outpatient medical visits totaling $1.009 billion; and 2) indirect costs including the loss of earnings due to time away from work for caregivers totaling $619 million. in addition, willingness to pay for relief of symptoms or intangible costs equaled $2.6 billion (5) (6). prevalence of ad in children ad affects individuals of all ages and backgrounds. of the 16.5 million people in the u.s affected by ad, 9.6 million are children with 80% having onset of disease before 6 years of age (2). ad is known to predominantly impact industrialized nations. in the u.s, the prevalence of ad has risen from 8% to 12% since 1997. furthermore, studies show that there is a 50% lower risk for developing ad in children who were born in countries outside of the us, but the risk increases after living in the us for a decade (2). there is greater prevalence in households with increased incomes and higher education (6). additionally, smaller family sizes and residing in urban and metropolitan areas appear to increase the prevalence of ad (6). skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 464 public health significance of managing and preventing complications of ad in children ad produces a substantial public health burden, partly driven by its impact on the quality of life but also resulting from the high healthcare costs and utilization associated with disease management. the relentless symptoms decrease productivity and the desire for relief produces direct, indirect, and tangible costs for both patients and payers. amongst skin diseases, ad demonstrates the fourth highest quality of life-related costs (5). compared to hypertension and diabetes, ad in the united states has $371-$489 greater out-of-pocket cost per person per year (2). unfortunately, these costs represent an even greater burden for the underprivileged. in fact, 17.6% of patients delay care and 13.1% of patients do not even seek medical care for ad due to concerns about health care expenses (2). in addition, 15.7% of patients who seek care are unable to pay the cost of prescriptions (2). identifying approaches to prevent and manage mild ad is a focus of public health measures. determinants of ad in children including the role of parents while studies regarding the public health burden imposed by ad define the geographical and socioeconomic influences on this condition, research must also focus on causative factors and determinants of disease severity. ad is certainly multifactorial involving a host of genetic and environmental influences. the genetic influence is supported by twin studies. (7). environmental antigens associated with ad include allergens associated with house-dust mites and food, as well as non-allergenrelated factors, such as irritating clothing material, staphylococcus aureus infections, microorganism exposure at a young age, and heat (8). environmental allergens impacted by socioeconomic and demographic influences, shift a genetically predisposed individual towards the development of an ad immune response. several factors are associated with more severe disease: neglected housing, parental education level, general health of the mother, parental emotional health, lower household income, single parent home, and being the firstborn child (9). as modifiable determinants such as these are determined, specifically those linked to the role of parenting, new management strategies can be developed. self-management of ad in children: challenges the current standard of care for ad involves the use of topical corticosteroids to reduce skin inflammation, emollients to promote skin hydration and protect the skin barrier, and efforts to avoid inflammatory triggers. despite these efforts, many patients report untreated symptoms half of the time during flares (10). additionally, fewer than 25% of both caregivers and patients report confidence in their ability to control ad flares (10). it is, therefore, important to consider the factors that lead to non-adherence to treatments. a cross-sectional survey of mothers and children with ad in tokyo determined both disease severity and a stable, healthy doctorpatient relationship predicted adherence to treatment (11). the trusted physician may mitigate misunderstandings related to treatment regimens. another study assessed the relationship between the concern for topical steroid side effects and adherence in ad patients. unwarranted concern of side effects led 39% of patients and caregivers to use topical corticosteroids for shorter durations and less frequently than recommended. up to 66% of patients reported using topical steroids only as a last resort (10). in fact, the biggest challenge skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 465 faced in self-management of ad results from a gap between physicians and patient’s/caregiver’s knowledge about treatment. at least two-thirds of caregivers and patients believe that the ability to confidently control ad is the most important determinant of quality of life (10). this individual belief or sense of confidence in the ability to control a situation is termed “selfefficacy.” when parents believe they have the ability to successfully control the ad of their child, this is known as parental selfefficacy (12). as research surrounding childhood chronic diseases, such as asthma and cystic fibrosis, has advanced the concept of parenteral self-efficacy (pse). pse predicts the performance of management tasks in parents of children with chronic disease and has been found to predict morbidity (12). thus, the perceptions of patients and caregivers about the management of their ad are associated with their self-efficacy and likelihood of treatment adherence. for this reason, it would be expected that ad management could be improved by testing educational methods that utilize self-efficacy and task performance measurements as indicators of efficacy (12, 13). educational interventions for parental involvement in self-management of ad in children for over three decades, educational interventions have been developed to effectively manage ad. these have focused on knowledge acquiring processes, including teaching and learning utilizing reinforcement. the goal of these interventions is to give patients a better understanding of their disease processes and management principles by providing treatment instructions and prevention strategies related to the effective management of ad (14). they also aim to provide parents with self-efficacy, which has the potential to predict their performance of disease-specific management tasks (12). a meta-analysis of educational intervention trials in ad patients published in 2020 was one of the first to demonstrate the relationship between education and managing ad on a large scale. using a comprehensive search of databases, researchers identified studies that met the following characteristics and conditions: participants with ages from one month to 18 years, presence of a health education group and a control group, and outcomes that were measured using scorad (severity scoring of atopic dermatitis index) and quality of life indices such as infants’ dermatology quality of life index (idqol) (15, 16). these studies demonstrated that health education interventions played a significant role on idqol score, increasing at 3 and 6 months and scorad scores significantly decreased at 6 and 12 months when compared to a control group (15). however, these trials were carried out in different countries and failed to include characteristics such as patient demographics and the education strategy utilized. additional efficacy studies followed by multi-centric effectiveness educational trials with large sample sizes are needed (15). limitations of educational interventions although positive outcomes have been associated with educational programs, there are limitations with current educational approaches and the tools used to measure their success. specifically, parental educational interventions for children with ad often do not incorporate the education of the child. this is a missed opportunity since ad outcome measures are almost always childcentered (severity of disease and patient quality of life). on the other hand, mitchell et skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 466 al. noted that child-centered outcomes may be less sensitive indicators of success when education is parent-focused (12). thus, parent-specific outcome variables such as self-efficacy and outcome expectations are more reliable and valid indicators when evaluating interventions with parental focus. in a systematic review, ersser et al. support a similar notion by emphasizing that parents are the primary emphasis of the educational modalities, while children are the primary emphasis of psychological approaches (14). this systematic review by ersser et al. analyzed the two main adjunctive approaches to pharmaceutical therapy for ad: psychological and educational interventions. both educational and psychological interventions, when used as separate entities, have major drawbacks and indicate the need for more comprehensive intervention strategies. specifically, educational interventions that lack a psychologic interventional component are flawed and fail to provide the tested approaches that allow parents to develop long-lasting, meaningful behavioral changes in their children with ad. the missing elements that are required to induce behavior change include factors such as participant motivation with set goals, the provision of confidence and autonomy in decision‐ making, and the development of problemsolving skills that promote the achievement of goal-directed action plans (14). to improve educational interventions, methods must be developed that draw a connection between intention and behavior change. self-efficacy theory-based educational interventions provide patients with the knowledge, behavior-specific skills, and confidence needed to cope with their condition successfully (14). for example, an elementary education program focused on changing physical activity through the social cognitive theory should have concrete goals. after the intervention, 80% of the participants should demonstrate improvement in: 1) physical activity expectations; 2) physical activity self-efficacy scoring; and 3) physical activity self-control score (17). the objectives listed here would not be measured in an interventional program that is purely educational. studies on ad should not rely so heavily on self-management, and a comprehensive intervention creating a longlasting behavioral impact is a more important goal. application of behavioral theories in the management of ad chronic diseases require life-long selfmanagement techniques that are adaptable, yet durable. educational programs seek to understand why patients develop healthpromoting behaviors, leading to hopefully more effective interventions (18). several theories have evolved to promote healthy behaviors. the 2010 annual review of public health lists the most popular approaches: the health belief model (hbm), , social cognitive theory (sct), transtheoretical model (ttm) and social-ecological model (sem) (18). the hbm focuses on the perception of risks and benefits to disease prevention and development. on the other hand, the ttm and sct are related to disease prevention and management. while the ttm outlines stages of change for successful health behaviors, the sct promotes change based on an individual and family experiences. finally, the social ecological model emphasizes the environments that are most suitable for changes to take place. the berlin parental educational program uses behavioral theory and utilizes the underlying principles of the social learning theory (slt, the older version of sct) to identify behavioral elements required skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 467 for the patient to adapt and gain the knowledge necessary for change (19). in addition, the slt stresses self-efficacy as an essential component in developing cognitive changes that facilitate desired health behaviors (19). with the goal of improving parent’s self-management skills, these principles are integrated with educational objectives regarding the medical, nutritional, and psychological basis for effective management of ad (19). the six-week program consists of weekly 2-hour sessions run by pediatricians, psychologists, and dieticians that incorporate educational objectives (medical, psychological, and nutritional information) with skill training and open group discussions (19). medical topics emphasize the causes and treatment of ad, appropriate over-the-counter skin care, and the avoidance of environmental triggers. the psychological aspect of the program highlights the management of stress and the itch-scratch cycle while providing coping mechanisms for both the child and family. finally, nutritional topics assess the associated risks and benefits of dietary programs, avoidance of allergies tied to ad, and provide nutritional recommendations. slt is tied to educational goals utilizing the following techniques: 1) skills training that includes goal setting and putting desired behaviors into small steps; and 2) modeling; 3) positive reinforcement; and, 4) monitoring of behaviors and environmental triggers (19). a randomized control trial utilizing the berlin educational program was instituted in 7 german hospitals. parents of children with ad were stratified by age of the child into 3 different experimental groups. results demonstrated that, compared to control groups, all three intervention groups had significant improvements in symptom severity (20). a case for the multi-theory model (mtm) of health behavior change for educational interventions for parental involvement in self-management of ad in children evidence shows that incorporating theoretical fundamentals into interventions improves overall efficacy (19). furthermore, the application of interventions based on multiple theories can result in additive impacts on efficacy (18). the berlin parental educational program which focused on ad and several other public health interventions, confirmed that utilizing behavioral theories in conjunction with educational interventions can instill long-standing principles of disease self-management. researchers, however, may refrain from incorporating multiple theories for several reasons. for example, measuring and analyzing constructs of certain health behavior theories is challenging (18). teaching large amounts of information may overshadow the role of theory in an intervention (18). finally, considering the number of theoretical frameworks in the literature today, it may be impossible to find one that suits an educational interventional program perfectly. the ideal theory will predict health behavior change that is both immediate and long-term and produced by sufficient evidence with adequate predictive power. the constructs must be modifiable and retain value for individuals, groups, and the community across various cultures. (21, 17). regrettably, the perfect theory has yet to be developed. for this reason, the slt theory, which expands upon multiple disciplines and self-efficacy, is frequently chosen for health interventions designed to affect behavior changes in conditions such as ad. using the slt theory alone, however, disregards important elements which could be incorporated with behavioral theories. for example, the ttm model is most specific to behavior change compared to all other health promotion and health education approaches skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 468 (21). using the ttm, however, is associated with some disadvantages. for example, because ttm uses arbitrary stages, it can be quite ambiguous, making it difficult to apply several of its constructs (21). furthermore, although it is inherent to behavior change, the ttm has an underlying context of psychotherapy and fails to address health education measures (21). hbm, while focused on health education, addresses change at the level of the individual and has limited predictability. the shortcomings of individual-level behavioral theories have led to multi-theory models of health education intervention in chronic diseases such as ad. health behavior change is dependent on initiating modification and maintaining the behavioral change. sharma emphasizes the constructs initiating change are not the same as the constructs needed to maintain behavior change (21). existing theories which explain behavior change do not make this distinction and may account for lower predictive power (21). this led to the multitheory model (mtm) for health behavior change pulling together several constructs that are derived from successful behavioral theories, while permitting each to operate independently from one another. the model derived by sharma is composed of six constructs, three focused on initiating behavior change and three directed at maintaining behavior change. the constructs which address initiating behavior change are: a dialogue about the pros and cons of behavior change, self-efficacy and its impact on confidence, and components of the physical environment that make a behavioral change feasible (17; see figure 1 for adaptation of this model to self-management behaviors for atopic dermatitis). the constructs which maintain change are emotional transformation, reflection and reflective action around change, and a social environment with a support system for behavioral change (21; see figure 2 for adaptation of this model to self-management behaviors for atopic dermatitis). interventions for parents of children with ad must initiate and maintain behavior changes. although the mtm for health behavior has not been studied specifically for interventions in ad, it has been utilized for other health interventions that identified predictive factors associated with initiation and sustenance of these interventions. a cross-sectional study using mtm in the us demonstrated the model’s ability to predict both initiation and maintenance of anxietyreducing behaviors in students (22). the analysis was performed with mtm constructs used as the independent variables and intention to initiate and maintain relaxation behaviors as dependent variables. there were significant associations between behavioral confidence with the initiation of relaxation behavior and emotional transformation with sustenance (22). a similar cross-sectional study sought to identify predictive factors for ghanaian adolescents’ intention receive hpv vaccination (23). changes in physical environment was found to be a significant predictor of intention to accept the vaccine (initiation). two significant predictors for completing the recommended doses of hpv vaccination (sustenance) were practice for change and emotional transformation. skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 469 figure 1. diagrammatic depiction of the initiation model of mtm for changes in self-management behaviors related to atopic dermatitis figure 2. diagrammatic depiction of the sustenance model of mtm for changes in self-management behaviors related to atopic dermatitis skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 470 interestingly, while physical environment and practice for change were found to be significant predictors in this study, another study utilizing the mtm model for anxiety in veterinary students found neither to be predictive. differences in the external environment in each study may explain this phenomenon. the notion that emotional transformation remained significant for both studies with very different demographics indicates the possibility that this may be a more universal construct for predicting intention to change. in addition to identification of constructs which may be positive predictors for initiation and sustenance, studies have also studied the extent to which certain constructs yield positive results. in a study that applied the multi-theory model (mtm) to predict water consumption in lieu of sugar-sweetened beverages (ssbs), researchers found that changes in the physical environment and behavioral confidence were associated with a 61.8% of the variance in the commencement of drinking water behavior instead of ssbs (24). constructs of emotional transformation and practice for change were associated with a 58.3% variance in the sustenance of drinking water instead of ssbs (24). these findings provide additional support that changes in the physical environment and behavioral confidence as significant predictors for initiation and practice for change and emotional transformation as significant predictors for sustenance. utilization of the mtm for health behavior intentions goes beyond the identification of predictors of behavioral change. several studies have assessed interventions using mtm models and yielded positive results. one study tested the efficacy of an mtmbased intervention on starting and maintaining physical activity among african american women and compared it to a traditional intervention based on mere knowledge acquisition (25). when compared to the knowledge-based intervention, results showed the mtm-based intervention was associated with significant increases in the minutes of physical activity, reductions in waist circumference, and modification of changes in the physical environment (25). while these results demonstrate the possibility for successful mtm based interventions, they also demonstrate the impact of modifying the environment based on demographics. another study demonstrated the efficacy of mtm-based educational interventions on waterpipe smoking in male adolescent students (26). a statistically significant decrease in the frequency of waterpipe smoking in the intervention group was noted. the study also went further comparing constructs between study and control groups. participatory dialogue, behavioral confidence, practice for change, and emotional transformation were all significantly different in the intervention arm compared to the control arm, demonstrating a clear connection between the success of the intervention and constructs of the mtm model for health behavior. implications for clinical practice since ad is largely a condition of childhood, the role of a parent/caregiver is critically important in disease management. if adequate attention is not given to the parentrelated exacerbating factors of ad (such as emotional stress, inappropriate skin care technique, dietary restrictions, etc.), even patients with the most comprehensive management plans may fail to achieve significant improvement (27). the factors listed above, and knowledge and beliefs skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 471 surrounding medications used in treatment regimens can be targeted in educational intervention programs. furthermore, health educational interventions have shown efficacy in the management of several chronic diseases that impact adults directly, and as a result, have been used to target and improve the role of parents in managing ongoing childhood conditions such as ad. in addition to knowledge about the condition itself, other parental factors such as emotional health and self-efficacy are important determinants in ad (9, 10). furthermore, since ad is an ongoing condition, a model that instills a long-standing behavioral change is needed. similar to management principles for chronic conditions impacting adults, managing atopic eczema requires adaptive changes in health behavior promoting action of the patient and the caregiver (14). a comprehensive approach includes psychological and educational strategies as adjuncts to conventional therapy (14). for this reason, educational models that incorporate theories of behavior have the ability to make a more permanent and effective impact on various conditions requiring treatment adherence. of course, no single behavioral theory targets both initiation and maintenance of health behavioral change (21). in addition, there are several behavioral constructs that underlie a caregiver’s impact on ad that can be addressed by various behavior theories therefore, mtm models for health education interventions may be of particular importance (18). though not yet investigated in ad, mtm models for other health behavior interventions have shown evidence predictive of positive behavior change. in summary, mtm models may be important in the study of ad because they not only bring together various behavioral constructs that affect the role of caregivers but also initiation and sustenance in educational health interventions. recommendations for research few studies exist focusing on behavioral theories that impact educational interventions for managing ad, and no studies have evaluated the use of an mtm model for ad interventions. to strengthen the argument for using this model in the study of ad, the impacts of behavioral theories in chronic diseases were analyzed in this article. independent behavioral theories on educational interventions for ad suggest that utilizing multiple theories may lead to more successful interventions. in addition, the outcome variables used to assess the results should reflect both disease severity in the patient and behavior changes induced by the intervention. thus, behavioral constructs that are significant predictors for initiation and sustenance should be identified and differentiated. this may be done with studies modeled after those that test the efficacy of the mtm model in predicting health behavioral change (22, 23). finally, the results of these studies can be used to develop and assess interventions utilizing the mtm model to ensure that parents are able to manage their child’s ad effectively. (25, 26) conflict of interest disclosures: robert t. brodell has participated in multi-center clinical trials with: genentech, janssen pharmaceuticals, corrona psoriasis registry, novartis, and glaxo-smith-kline. he is also associate editor of the journal of the american academy of dermatology and editor-inchief of practice update: dermatology. kayla penny, manoj sharma, amy e. flischel, and vinayak k. nahar have no conflicts of interest. funding: none corresponding author: vinayak k. nahar, md, phd, ms department of dermatology school of medicine university of mississippi medical center 2500 north state street – l216 skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 472 jackson, ms 39216 usa (601) 495-5876 naharvinayak@gmail.com references: 1. weidinger, s., beck, l.a., bieber, t. et al. atopic dermatitis. nat rev dis primers 4, 1 (2018). https://doi.org/10.1038/s41572-018-0001-z 2. eczema facts. national eczema association. retrieved june 1, 2020, from https://nationaleczema.org/research/eczemafacts/ 3. chamlin, s. l., frieden, i. j., williams, m. l., & chren, m. m. (2004). effects of atopic dermatitis on young american children and their families. pediatrics, 114(3), 607-611 4. mian, m., silfvast-kaiser, a. s., paek, s. y., kivelevitch, d., & menter, a. (2019). a review of the most common dermatologic conditions and their debilitating psychosocial impacts. international archives of internal medicine, 3, 018 5. drucker, a. m., wang, a. r., li, w. q., sevetson, e., block, j. k., & qureshi, a. a. (2017). the burden of atopic dermatitis: summary of a report for the national eczema association. journal of investigative dermatology, 137(1), 26-30 6. silverberg, j. i. (2017). public health burden and epidemiology of atopic dermatitis. dermatologic clinics, 35(3), 283-289. 7. cookson, william o.c.m.; moffatt, miriam f. the genetics of atopic dermatitis, current opinion in allergy and clinical immunology: october 2002 volume 2 issue 5 p 383-387 8. williams, h., 2005. atopic dermatitis. new england journal of medicine, 352(22), pp.2314-2324. 9. silverberg ji, simpson el. associations of childhood eczema severity: a us population-based study. dermatitis. 2014;25(3):107-114. doi:10.1097/der.0000000000000034 10. 1zuberbier, t., orlow, s. j., paller, a. s., taïeb, a., allen, r., hernanz-hermosa, j. m., ... & simon, j. c. (2006). patient perspectives on the management of atopic dermatitis. journal of allergy and clinical immunology, 118(1), 226-232. 11. ohya, y., williams, h., steptoe, a., saito, h., iikura, y., anderson, r., & akasawa, a. (2001). psychosocial factors and adherence to treatment advice in childhood atopic dermatitis. journal of investigative dermatology, 117(4), 852-857. 12. mitchell, a. e., & fraser, j. a. (2014). management of atopic dermatitis in children: evaluation of parents' self-efficacy, outcome expectations, and self-reported task performance using the child eczema management questionnaire. neonatal, paediatric and child health nursing, 17(2), 16-22. 13. ersser sj, latter s, sibley a, satherley pa, welbourne s. psychological and educational interventions for atopic eczema in children. cochrane database syst rev. 2007;(3):cd004054. 14. ersser, s. j., cowdell, f., latter, s., gardiner, e., flohr, c., thompson, a. r., ... & drury, a. (2014). psychological and educational interventions for atopic eczema in children. cochrane database of systematic reviews, (1). 15. li, y., han, t., li, w., li, y., guo, x., & zheng, l. (2020). efficacy of health education on treatment of children with atopic dermatitis: a meta-analysis of randomized controlled trials. archives of dermatological research, 1-11. 16. charman c, williams h. outcome measures of disease severity in atopic eczema. arch dermatol. 2000;136(6):763–769. doi:10.1001/archderm.136.6.763 17. sharma m. theoretical foundations of health education and health promotion. sudbury: jones & bartlett learning; 2017 18. glanz, k., & bishop, d. b. (2010). the role of behavioral science theory in development and implementation of public health interventions. annual review of public health, 31, 399-418 19. wenninger, k., kehrt, r., von rüden, u., lehmann, c., binder, c., wahn, u., & staab, d. (2000). structured parent education in the management of childhood atopic dermatitis: the berlin model. patient education and counseling, 40(3), 253-261 20. staab d, diepgen tl, fartasch m, et al. age related, structured educational programmes for the management of atopic dermatitis in children and adolescents: multicentre, randomised controlled trial. bmj. 2006;332(7547):933-938. doi:10.1136/bmj.332.7547.933 21. sharma, m. (2015). multi-theory model (mtm) for health behavior change. webmed central behaviour, 6(9), wmc004982 22. nahar, v. k., wells, j., davis, r. e., johnson, e. c., johnson, j. w., & sharma, m. (2020). factors associated with initiation and sustenance of stress management behaviors in veterinary students: testing of multi-theory model (mtm). international journal of environmental research and public health, 17(2), 1-10 23. asare, m., agyei-baffour, p., lanning, b. a., barimah owusu, a., commeh, m. e., boozer, k., ... & paskett, e. d. (2020). multi-theory model and predictors of likelihood of accepting the series of hpv vaccination: a cross-sectional study among ghanaian adolescents. international journal of environmental research and public health, 17(2), 571. 24. sharma, m., catalano, h. p., nahar, v. k., lingam, v., johnson, p., & ford, m. a. (2017). using multimailto:naharvinayak@gmail.com about:blank about:blank about:blank skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 473 theory model (mtm) of health behavior change to predict plain water consumption instead of sugar sweetened beverages. journal of research in health sciences, 17(1), e00370 25. hayes, t., sharma, m., shahbazi, m., sung, j. h., bennett, r., & reese-smith, j. (2019). the evaluation of a fourth-generation multi-theory model (mtm) based intervention to initiate and sustain physical activity in african american women. health promotion perspectives 26. bashirian, s., barati, m., sharma, m., abasi, h., & karami, m. (2019).water pipe smoking reduction in the male adolescent students: an educational intervention using multi-theory model. journal of research in health sciences, 19(1), e00438 27. lebovidge, j. s., elverson, w., timmons, k. g., hawryluk, e. b., rea, c., lee, m., & schneider, l. c. (2016). multidisciplinary interventions in the management of atopic dermatitis. journal of allergy and clinical immunology, 138(2), 325-334. synopsisobjective to assess the impact of certolizumab pegol on dermatology life quality subdomains over the course of 144 weeks of treatment in patients with moderate to severe plaque psoriasis. introduction • certolizumab pegol (czp) is an fc-free, pegylated, anti-tumor necrosis factor agent that has shown durable clinical improvements over 144 weeks of treatment in patients with moderate to severe plaque psoriasis (pso).1,2 • pso can negatively impact health-related quality of life (hrqol), with links to pain and discomfort, social stigmatization, and psychological distress.3 therefore, it is important to understand whether clinical responses translate into long-term improvements in hrqol. • here, we present dermatology life quality index (dlqi) results over 144 weeks of czp treatment to evaluate the impact of czp across different dlqi subdomains and to expand upon dlqi remission rates (dlqi 0/1) previously reported.1 methods • data were pooled from cimpasi-1 (nct02326298) and cimpasi-2 (nct02326272), phase 3 trials in adults with moderate to severe pso; detailed study designs have been described previously (figure 1).1,4 • dlqi by initial czp randomization group through week 144 is reported, as observed. • we report: – absolute scores for total dlqi and dlqi subdomains through weeks 0–144. – rate of dlqi subdomain remission, defined as a score of 0, indicating no impact of skin disease on that concept, at weeks 48 and 144. results • baseline demographics are shown in table 1 and patient numbers with available dlqi data at each week are shown in table 2. • improvements in total dlqi observed over the first 48 weeks of czp treatment were durable through to week 144 (figure 2). • across all dlqi subdomains, baseline mean scores were similar between treatment groups (table 3). • at baseline, the dlqi subdomains with the highest scores were symptoms and feelings, daily activities, and leisure, indicating greatest impact of disease on these areas (table 3). • improvements in the scores for these dlqi subdomains over the first 48 weeks were durable through to week 144 for both treatment groups (figure 3). • remission rates at week 48 across subdomains of interest were also maintained until week 144 for both treatment groups (figure 4). a. blauvelt,1 r.b. warren,2 k. reich,3 f. brock,4 f. fierens,5 v. ciaravino,6 m. lebwohl7 bmi: body mass index; bsa: body surface area; czp: certolizumab pegol; dlqi: dermatology life quality index; il: interleukin; oc: observed case; ld: loading dose; pasi: psoriasis area and severity index; pga: physician’s global assessment; pso: psoriasis; q2w: every two weeks; sd: standard deviation; tnf: tumor necrosis factor. remission is defined as a score of 0, indicating no impact of skin disease on that concept. table 2 patient numbers with available dlqi data table 3 baseline dlqi subdomain scores (oc) figure 1 cimpasi-1 and cimpasi-2 study design figure 2 total dlqi through weeks 0–144 (oc)table 1 demographic and baseline characteristics figure 4 remission rates for dlqi subdomains at week 48 and 144 (oc) figure 3 absolute scores by dlqi subdomain through weeks 0–144 (oc) aczp 200 mg q2w patients received czp 400 mg q2w at weeks 0, 2 and 4. adults with pso ≥6 months (pasi >12, bsa affected ≥10% and pga ≥3 on a 5-point scale) were enrolled. at week 48, patients entering the open-label period from blinded treatment received czp 200 mg q2w, with subsequent dose adjustments permitted. patients not achieving pasi 50 at week 16 entered the escape arm for treatment with czp 400 mg q2w; at week 48 these patients continued to receive czp 400 mg q2w or, if they achieved pasi 75, could have had their dose reduced at the investigator’s discretion. aloading dose of czp 400 mg q2w at weeks 0, 2 and 4 or weeks 16, 18 and 20. bdose adjustments were mandatory or at the discretion of the investigator, based on pasi response. aczp 200 mg q2w patients received czp 400 mg q2w at weeks 0, 2 and 4. lower scores indicate greater quality of life. all subdomains are scored 0–6 with the exception of work and school and treatment which are scored 0–3. mean ± sd unless stated czp 400 mg q2w (n=175) czp 200 mg q2wa (n=186) all czp (n=361) age (years) 45.0 ± 12.9 45.6 ± 13.2 45.3 ± 13.0 male, n (%) 103 (58.9) 125 (67.2) 228 (63.2) bmi, kg/m2 31.2 ± 7.9 32.0 ± 7.8 31.6 ± 7.8 duration of pso (years) 18.5 ± 12.6 17.7 ± 12.9 18.1 ± 12.7 pasi 19.6 ± 7.3 19.2 ± 7.2 19.4 ± 7.3 bsa (%) 23.6 ± 14.3 23.5 ± 14.9 23.5 ± 14.6 pga score, n (%) 3: moderate 126 (72.0) 128 (68.8) 254 (70.4) 4: severe 49 (28.0) 58 (31.2) 107 (29.6) total dlqi 13.7 ± 6.9 14.3 ± 7.4 14.0 ± 7.1 prior biologic use, n (%) 59 (33.7) 62 (33.3) 121 (33.5) anti-tnf 40 (22.9) 44 (23.7) 84 (23.3) anti-il17 8 (4.6) 16 (8.6) 24 (6.6) anti-il-12/il-23 10 (5.7) 3 (1.6) 13 (3.6) mean ± sd czp 400 mg q2w (n=173) czp 200 mg q2wa (n=183) all czp (n=356) symptoms and feelings 4.1 ± 1.4 4.2 ± 1.5 4.2 ± 1.4 daily activities 3.2 ± 1.7 3.2 ± 1.9 3.2 ± 1.8 leisure 2.4 ± 1.9 2.7 ± 2.0 2.5 ± 2.0 work and school 0.9 ± 1.0 0.9 ± 1.0 0.9 ± 1.0 personal relationships 1.9 ± 1.9 2.0 ± 1.9 1.9 ± 1.9 treatment 1.2 ± 1.1 1.3 ± 1.1 1.3 ± 1.1 study week 0 2 8 12 16 24 32 48 60 72 84 96 108 120 132 144 czp 400 mg q2w 173 172 171 168 170 159 152 148 140 141 136 131 124 123 114 113 czp 200 mg q2w 183 183 173 177 174 164 159 151 142 138 130 128 124 119 106 110 institutions: 1oregon medical research center, portland, or; 2dermatology centre, salford royal nhs foundation trust, manchester nihr biomedical research centre, the university of manchester, manchester, uk; 3center for translational research in inflammatory skin diseases, institute for health services research in dermatology and nursing, university medical center hamburg-eppendorf and skinflammation® center, hamburg, germany; 4ucb pharma, slough, uk; 5ucb pharma, brussels, belgium; 6ucb pharma, colombes, france; 7icahn school of medicine at mount sinai, new york, ny presented at winter clinical 2021 virtual congress | january 16–24 conclusions improvements in total dlqi were durable from week 48 to week 144 across both czp treatment groups. this pattern was reflected in the dlqi subdomains (symptoms and feelings, daily activities, and leisure) which had the greatest impact on patients’ lives at baseline. durability of dlqi improvements among patients with moderate to severe plaque psoriasis treated with certolizumab pegol: three-year results from two phase 3 trials (cimpasi-1 and cimpasi-2) references: 1gordon k. bjd 2020; doi.org/10.1111/bjd.19393; 2blauvelt a. bjd 2020; doi.org/10.1111/bjd.19314; 3bhosle mj. health qual life outcomes 2006;4:35; 4gottlieb ab. jaad 2018;79:302–14.e6; 5finlay ay. clin exp dermatol 1994;19:210–6. author contributions: substantial contributions to study conception/design, or acquisition/analysis/interpretation of data: ab, rbw, kr, fb, ff, vc, ml; drafting of the publication, or revising it critically for important intellectual content: ab, rbw, kr, fb, ff, vc, ml; final approval of the publication: ab, rbw, kr, fb, ff, vc, ml. author disclosures: ab: scientific adviser and/or clinical study investigator for abbvie, allergan, almirall, athenex, boehringer ingelheim, bristol myers squibb, dermavant, eli lilly, forte, galderma, incyte, janssen, leo pharma, novartis, pfizer, rapt, regeneron, sanofi genzyme, sun pharma, and ucb pharma; paid speaker for abbvie; rbw: consulting fees from abbvie, almirall, amgen, arena, avillion, boehringer ingelheim, bristol myers squibb, celgene, eli lilly, janssen, leo pharma, novartis, pfizer, sanofi, and ucb pharma; research grants from abbvie, almirall, amgen, celgene, eli lilly, janssen, leo pharma, novartis, pfizer, and ucb pharma; kr: served as advisor and/or paid speaker for and/or participated in clinical trials sponsored by abbvie, affibody, almirall, amgen, avillion, biogen, boehringer ingelheim, bristol myers squibb, celgene, centocor, covagen, dermira, eli lilly, forward pharma, fresenius medical care, galapagos, gsk, janssen, kyowa kirin, leo pharma, medac, msd, miltenyi biotec, novartis, ocean pharma, pfizer, regeneron, samsung bioepis, sanofi, sun pharma, takeda, ucb pharma, valeant/bausch health, and xenoport; fb, ff, vc: employees of ucb pharma; ml: employee of mount sinai which receives research funds from abbvie, amgen, arcutis, boehringer ingelheim, dermavant, eli lilly, incyte, janssen, leo pharma, ortho dermatologics, pfizer, and ucb pharma; consultant for aditum bio, allergan, almirall, arcutis, avotres, birchbiomed, bmd skincare, boehringer ingelheim, bristol myers squibb, cara therapeutics, castle biosciences, corrona, dermavant, evelo, facilitate international dermatologic education, foundation for research and education in dermatology, inozyme pharma, leo pharma, meiji seika pharma, menlo, mitsubishi pharma, neuroderm, pfizer, promius/dr. reddy’s laboratories, serono, theravance, and verrica. acknowledgements: this study was funded by ucb pharma. we thank the patients and their caregivers in addition to the investigators and their teams who contributed to this study. the authors acknowledge mylene serna, pharmd, ucb pharma, smyrna, ga, usa and susanne wiegratz, msc, ucb pharma, monheim am rhein, germany for publication coordination, ruth moulson, mph, costello medical, london, uk and joe dixon, phd, costello medical, cambridge, uk for medical writing and editorial assistance and the costello medical design team for design support. all costs associated with development of this poster were funded by ucb pharma in accordance with the good publication practice (gpp3) guidelines. a) symptoms and feelings b) daily activities c) leisure d lq i re m is si o n r a te ( % ) 100 80 60 40 20 0 week 48 week 144 d lq i re m is si o n r a te ( % ) 100 80 60 40 20 0 week 48 week 144 d lq i re m is si o n r a te ( % ) 100 80 60 40 20 0 week 48 week 144 52.7 40.4 47.8 40.9 76.4 66.2 71.7 71.8 83.8 74.8 78.8 79.1 czp 400 mg q2w czp 200 mg q2wczp 400 mg q2w czp 200 mg q2w czp 400 mg q2w czp 200 mg q2w a) symptoms and feelings b) daily activities c) leisure open-label period with possible dose adjustment open-label period with possible dose adjustment open-label period with possible dose adjustment s u b d o m a in s c o re ( m e a n ) 6 5 4 3 2 1 0 s u b d o m a in s c o re ( m e a n ) 0 s u b d o m a in s c o re ( m e a n ) 0 czp 400 mg q2w czp 200 mg q2w czp 400 mg q2w czp 200 mg q2w czp 400 mg q2w czp 200 mg q2w 6 5 4 3 2 1 0 6 5 4 3 2 1 0 16 32 48 64 80 96 112 128 144 0 16 32 48 64 80 96 112 128 144 0 16 32 48 64 80 96 112 128 144 0.4 0.4 0.4 0.3 0.5 0.5 0.6 0.4 0.9 1.2 0.8 1.1 week weekweek open-label period with possible dose adjustment t o ta l d lq i (m e a n ) 30 25 20 15 10 5 0 czp 400 mg q2w czp 200 mg q2w 0 16 32 48 64 80 96 112 128 144 2.6 2.9 2.0 2.7 week the dlqi questionnaire is comprised of 10 questions, each providing a score of 0–3 where higher scores indicate a greater impact of skin on that aspect of a patient’s quality of life.5 here, we present analyses based on total dlqi and individual subdomains: the dlqi subdomains with the highest scores at baseline were symptoms and feelings, daily activities, and leisure. remission rates (score of 0) in these subdomains after 144 weeks of treatment for patients randomized to czp 400 mg q2w and czp 200 mg q2w were as follows: daily activities 71.7% 71.8% leisure 78.8% 79.1% symptoms and feelings 47.8% 40.9% czp 400 mg q2w czp 200 mg q2w itchy/sore/ painful stinging embarrassed/ self-conscious interference with shopping/home/ garden influence on clothes worn problems with partners/friends/ relatives any sexual di�culties • • • • • • • • • • a�ects social/ leisure activities makes it di�cult to do any sports symptoms and feelings daily activities personal relationships leisure prevents or causes problems with work or studying how much of a problem is treatment work and school treatment methods results improvements in dlqi among czp-treated patients were durable from week 48 to week 144. conclusion score range of 0–3 (1 question each) score range of 0–6 (2 questions each) <pasi 50 initial treatment period (double-blinded) screening maintenance period safety follow-up open-label extension period (dose adjustment possible)b lda 48week 32 152160 40 144 mandatory at the investigator's discretion withdrawal placebo q2w czp 400 mg q2w escape: open-label czp 400 mg q2w czp 200 mg q2w czp 200 mg q2w 1: 2 :2 ra n d o m iz a ti o n czp 400 mg q2w ≥pasi 50, <pasi 75 lda ≥pasi 75 <pasi 50 ≥pasi 75 ≥pasi 50 <pasi 75 <pasi 50 – withdrawn<pasi 50 – withdrawn ≥pasi 75 previously presented at fall clinical dermatology conference 2020 | november 13–15 skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 556 brief article calcipotriene 0.005%/betamethasone dipropionate 0.064% foam as a treatment for nail psoriasis: a case series shifa akhtar1, bs, mariana perez1, ba, jessica sharma1, bs, agnese canazza2, martin zaiac1,2, md 1 florida international university, herbert wertheim college of medicine, miami, fl 2 greater miami skin and laser center, mount sinai medical center, miami beach, fl an estimated 80-90% of psoriasis patients develop nail involvement, leading to decreased quality of life secondary to pain, activity restriction, and an increased risk of anxiety and depression.1 historically, topical treatments for nail psoriasis have been considered less effective due to limited penetration through the psoriatic nail plate and prolonged duration of use leading to poor patient adherence.2 while systemic approaches with newer biologic agents have demonstrated efficacy in the treatment of moderate to severe nail psoriasis, patients with disease limited to the nail may be reluctant to use systemic biologic agents as opposed to topical agents. though combined approaches with topical vitamin d analogues and steroids as creams and ointments have been well-documented as effective treatments for mild psoriasis of the nail, there is minimal literature regarding the use and efficacy of calcipotriene/betamethasone dipropionate in a foam vehicle.3,4 calcipotriene 0.005%/betamethasone dipropionate 0.064% (cal/bd) aerosol foam is indicated for the treatment of plaque psoriasis; we report our experience utilizing it as a treatment for psoriasis of the nail. three patients were evaluated in the dermatology clinic for psoriasis of the nail and treated with cal/bd aerosol foam, resulting in positive clinical outcomes. abstract combination topical corticosteroids and vitamin d analog treatments for nail psoriasis are widely used in cream and ointment vehicles, but patients may prefer a foam vehicle due to ease of application and favorable cosmetic appearance. calcipotriene 0.005%/betamethasone dipropionate 0.064% (cal/bd) aerosol foam is an fda approved therapy for plaque psoriasis, but may also be an effective treatment for nail psoriasis in a novel aerosol foam. we present a case series of 3 patients with mild to moderate nail psoriasis who responded positively to treatment with cal/bd aerosol foam applied 1-2 times daily to affected nails for at least 6 weeks. reduction of nail plate surface abnormalities and inflammation of the nail folds were assessed with clinical evaluation and dermoscopy, and documented with serial photography. while further research on the efficacy and safety of cal/bd aerosol foam as a treatment for nail psoriasis is needed, this report suggests its potential as a combination topical vitamin d analogue and high potency steroid in a foam vehicle. introduction case series skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 557 case 1: a 42-year-old male presented with adultonset, mild changes in nail appearance and texture. physical exam showed pitting in the left small fingernail, right thumbnail, and right index fingernail plates. a diagnosis of psoriasis of the nail was established, and global/microscopic pictures (executed with fotofinder medicam dermoscopy) were obtained to document the nail changes at baseline (fig 1, a). the patient was subsequently prescribed daily cal/bd aerosol foam. on fiveand ten-month followup exams, dermoscopy demonstrated a decrease in nail pits and an improvement of nail plate surface abnormalities (fig 1, b, c). figure 1. case 1 a) before treatment b) progressive improvement after five c) and ten months of treatment case 2: a 60-year-old female, diagnosed by her previous physician with onychomycosis of the thumb and toenails and treated with terbinafine and efinaconazole for three months, presented to our clinic due to a lack of improvement. exam demonstrated dystrophic nails involving multiple nail plates. unilateral curvature of the nail plate, onycholysis, and keratosis of the nail bed were all present (fig 2, a). dermoscopy demonstrated nail pitting, erythematous borders, and splinter hemorrhages in the distal nail bed (fig 2, b, c, d). terbinafine and efinaconazole were discontinued, and the patient was started on daily cal/bd aerosol foam for treatment of nail psoriasis. at six-week follow-up, she noted improved nail appearance but continued to complain of mild to moderate onychodystrophy and discomfort (fig 2, e). dermoscopy demonstrated a decrease in psoriatic pits, nail scaling, and erythematous borders (fig 2, f, g, h). cal/bd aerosol foam was increased to a twice daily application regimen with enhanced success. figure 2 case 2 a, b, c, d) before treatment e, f, g, h) marked improvement after six weeks of treatment case 3: a 47-year-old female with a history of plaque psoriasis presented to our clinic with mild to moderate discoloration and pitting of the right thumbnail and left small fingernail plates for the past year. physical exam demonstrated pitting and crumbling of the right thumbnail skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 558 and left small fingernail plates (fig 3, a). dermoscopy of the right thumbnail plate showed leukonychia, irregular thickening, salmon patches, and hyperkeratosis of the cuticle (fig 3 b, c). the patient was followed by rheumatology and pending initiation of a new biologic agent at the time of the visit, having discontinued apremilast due to gastrointestinal side effects. she was given cal/bd aerosol foam to be applied topically to the affected nails twice daily. at four-month follow-up, the patient was being treated with adalimumab and cal/bd aerosol foam and noted improvement in nail appearance (fig 3, d). dermoscopy demonstrated reduced inflammation in the posterior nail folds as well as decreased nail pitting in the re-growing nails (fig 3, e, f). figure 3. a, b, c) before treatment d, e, f) improvement after four months of treatment for the treatment of mild nail psoriasis, topical/intralesional corticosteroid monotherapy, topical vitamin d analog monotherapy, or combination therapy is commonly recommended. vitamin d is understood to exhibit immunomodulatory and antiproliferative effects, while corticosteroids exhibit anti-inflammatory effects, thus working synergistically when combined.5 the use of different vehicles aside from ointment in the topical treatment of nail psoriasis have been explored. eight percent clobetasol-17propionate in a colorless nail lacquer vehicle has produced favorable results, with one study of 15 patients demonstrating a reduction in nail alterations and in the modified psoriasis severity index by 78% compared to baseline.6 there are also case reports of refractory nail psoriasis treated successfully with cal/bd gel, with authors hypothesizing that the low viscosity of the lipophilic gel may reach the subungual gap and the gap beneath the proximal nail folds in affected nails.7 while topical therapies combining a corticosteroid and vitamin d analog are established treatments for nail psoriasis, there is scarce literature regarding the use of cal/bd aerosol foam. traditionally, ointments were the vehicle of choice, but the rising popularity of different formulations including creams, lotions, nail lacquers, and foams has provided more options for patients and clinicians. while patient adherence to treatment is essential in the successful management of psoriasis, around 40% of psoriasis patients report poor adherence to topical regimens and report that both psoriasis and its treatment interfere with their quality of life.8 notably, patients prefer foam vehicle solutions over creams, gels, and ointments for psoriasis treatment.9 therefore, substitution of the traditional ointment with a foam vehicle may improve adherence and subsequently result in greater positive patient outcomes, but further investigation is needed. the efficacy and safety of cal/bd foam for plaque psoriasis has been established, with randomized control trials demonstrating tolerability and increased remission time.10 a preliminary study of discussion skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 559 cal/bd in foam formulation for the treatment of nail psoriasis demonstrated it was welltolerated and lacked steroid-related adverse reactions, but larger clinical trials are underway to better establish its efficacy and tolerability for this indication.11 our case series demonstrates the potential of cal/bd aerosol foam as a treatment for nail psoriasis. this can be a desirable option for patients with contraindications to systemic therapy or a preference for topical therapy in a foam vehicle. further investigation with an adequate sample of patients should be undertaken to better determine its side effects and efficacy. conflict of interest disclosures: none funding: none corresponding author: shifa akhtar, bs florida international university herbert wertheim college of medicine 11200 sw 8th st, ahc-2 miami, fl, 33199 usa phone: (305) 348-0570 email: sakht008@med.fiu.edu references: 1. de jong em, seegers ba, gulinck mk, boezeman jb, van de kerkhof pc. psoriasis of the nails associated with disability in a large number of patients: results of a recent interview with 1,728 patients. dermatology. 1996;193(4):300-3. doi:10.1159/000246274 2. rigopoulos d, baran r, chiheb s, et al. recommendations for the definition, evaluation, and treatment of nail psoriasis in adult patients with no or mild skin psoriasis: a dermatologist and nail expert group consensus. j am acad dermatol. jul 2019;81(1):228-240. doi:10.1016/j.jaad.2019.01.072 3. rigopoulos d, gregoriou s, daniel iii cr, et al. treatment of nail psoriasis with a two-compound formulation of calcipotriol plus betamethasone dipropionate ointment. dermatology. 2009;218(4):338-41. doi:10.1159/000202179 4. rigopoulos d, ioannides d, prastitis n, katsambas a. nail psoriasis: a combined treatment using calcipotriol cream and clobetasol propionate cream. acta derm venereol. 2002;82(2):140. doi:10.1080/00015550252948220 5. tan es, chong ws, tey hl. nail psoriasis: a review. am j clin dermatol. dec 1 2012;13(6):375-88. doi:10.2165/11597000000000000-00000 6. sánchez regaña m, márquez balbás g, umbert millet p. nail psoriasis: a combined treatment with 8% clobetasol nail lacquer and tacalcitol ointment. j eur acad dermatol venereol. aug 2008;22(8):963-9. doi:10.1111/j.14683083.2008.02679.x 7. takama h, ando y, yanagishita t, ohshima y, akiyama m, watanabe d. two cases of refractory nail psoriasis successfully treated with calcipotriol plus betamethasone dipropionate gel. j dermatol. may 2020;47(5):e211-e213. doi:10.1111/13468138.15314 8. richards hl, fortune dg, o'sullivan tm, main cj, griffiths ce. patients with psoriasis and their compliance with medication. j am acad dermatol. oct 1999;41(4):581-3. 9. housman ts, mellen bg, rapp sr, fleischer ab, jr., feldman sr. patients with psoriasis prefer solution and foam vehicles: a quantitative assessment of vehicle preference. cutis. dec 2002;70(6):327-32. 10. lebwohl m, kircik l, lacour jp, et al. twiceweekly topical calcipotriene/betamethasone dipropionate foam as proactive management of plaque psoriasis increases time in remission and is well tolerated over 52 weeks (pso-long trial). j am acad dermatol. may 2021;84(5):1269-1277. doi:10.1016/j.jaad.2020.09.037 11. gregoriou s, sidiropoulou p, tsimpidakis a, et al. treatment of nail psoriasis with calcipotriol/betamethasone dipropionate foam versus pulse dye laser: an unblinded, intra-patient, left-to-right prospective study. j eur acad dermatol venereol. sep 2020;34(9):e519-e520. doi:10.1111/jdv.16426 conclusion skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 135 brief article successful dupilumab treatment of atopic dermatitis in a liver transplant patient amanda krenitsky, md1, sairekha ravichandran, md1,2, joel cohen, bs1 jonathan braue, md3, lilia correa-selm, md1,2 1 university of south florida, department of dermatology and cutaneous surgery, tampa, fl 2 h. lee moffitt cancer center, department of cutaneous oncology, tampa, fl 3 scully welsh cancer center, cleveland clinic indian river hospital, department of dermatology and cutaneous oncology, vero beach, fl atopic dermatitis (ad) in liver transplant (lt) recipients is well-documented, despite frequent use of immunosuppressants in these patients. in a liver transplant population, the prevalence of ad in children and adults is 27.6% and 10.3%, respectively.1 however, there is little literature regarding treatment of this population, and standard regimens are not well-defined.2-4 here, we report a case of successful treatment of ad in an orthotopic lt patient with dupilumab. a 65-year-old caucasian female presented with 2-year history of pruritic eruption involving the extremities. medical history was significant for hypertension, gastroesophageal reflux, and orthotopic liver transplantation 17 years prior for which she was receiving tacrolimus. there was no known personal, family, or donor history of atopy. physical examination revealed pruritic, hyperkeratotic, scaly papules and lichenified plaques involving flexural surfaces of the bilateral upper and lower extremities. biopsy revealed spongiotic dermatitis with eosinophils, consistent with atopic dermatitis versus allergic contact dermatitis versus other id reaction. patch testing was positive for methyldibromo glutaronitrile, benzalkonium chloride, and benzophenone. despite strict allergen avoidance and trials of varying-potency topical, intramuscular, and oral corticosteroids, the patient experienced continued pruritus and repeated flares. phototherapy was relatively contraindicated secondary to patch-test proven concomitant photoallergic contact dermatitis. furthermore, use of immunosuppressants such as methotrexate abstract atopic dermatitis (ad) in liver transplant (lt) recipients is well-documented, despite frequent use of immunosuppressants in these patients. in a liver transplant population, the prevalence of ad in children and adults is 27.6% and 10.3%, respectively.1 however, there is dearth of literature regarding treatment of this population, and standard regimens are not well-defined.2-4 here, we report a case of successful treatment of ad in an orthotopic lt patient with dupilumab. introduction case report skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 136 and cyclosporine were contraindicated in this patient, due to lt status with concern for additional hepatotoxic agents and her pre-existing hypertension, respectively. after discussion with the patient’s care team, the patient was started on a dupilumab regimen for persistent atopic dermatitis, with an initial loading dose of 600 milligrams followed by 300 milligrams every two weeks. complete clearance of the rash, reduced flares, and ninety percent improvement in subjective pruritus were noted within one month and sustained throughout two additional years of treatment. the hepatic function panel and immunosuppressant levels were monitored monthly for three months, then every three months after initiation of dupilumab. treatment was welltolerated and no issues with hepatic function, immunosuppressant levels, or graft-related complications were reported. liver transplant portends a significantly higher risk of post-transplant allergy, autoimmunity, and immune mediated disorders than other solid-organ transplants (40% vs 1.3%).7 exaggerated th2-mediated inflammation secondary to suppression of the th1 immune pathway by calcineurin inhibitors (i.e., tacrolimus) is one proposed mechanism. to this regard, inhibition of the th2 response may offer a promising approach to the treatment of these patients. dupilumab, a monoclonal antibody that decreases th2-mediated inflammation by selectively blocking il-4 and il-13 signaling, has become an important component in the management of inflammatory and autoimmune diseases. additionally, dupilumab enhances skin repair by increasing epidermal barrier proteins.5since fda approval, the use of dupilumab in the treatment of ad is well-established, with fewer contraindications and a more favorable side effect profile than traditional immunosuppressants.5,6 while there are cases reporting safe and efficacious treatment of ad with dupilumab in liver, heart, and kidney transplant patients, its use in this setting has not been studied in clinical trials.2-4 we present a case of dupilumab treatment of ad with superimposed allergic contact dermatitis in an orthotopic lt patient in the setting of posttransplant immunosuppressive therapy, demonstrating favorable clinical response and good side effect profile, maintained for two subsequent years. prior to the dupilumab trial, this patient’s condition was refractory to several treatments despite considerable immunosuppression with transplant medications. as such, dupilumab may be considered a viable treatment option among solid-organ transplant patients with ad unresponsive to topical treatments, phototherapy, and traditional immunosuppressants. conflict of interest disclosures: dr. correa is a consultant for accutec blades funding: none corresponding author: amanda krenitsky, md university of south florida, 12901 bruce b downs blvd tampa, fl 33612 phone: 813-493-3034 fax : 813-974-4272 email: akrenitsky1@usf.edu references: 1. topal e, çatal f, selimoğlu ma, et al. acquired atopic disease after liver transplantation in children; similarities to and differences from adults: a preliminary study. eur j gastroenterol discussion conclusion mailto:akrenitsky1@usf.edu skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 137 hepatol. sep 2014;26(9):1055-9. doi:10.1097/meg.0000000000000142 2. ludriksone l, elsner p, malessa c, settmacher u, schliemann s. effectiveness and safety of dupilumab for atopic dermatitis in a liver transplant recipient: a case report. j dtsch dermatol ges. jul 2020;18(7):740-742. doi:10.1111/ddg.14074 3. kha c, raji k, chisolm s. treatment of atopic dermatitis with dupilumab in a renal transplant patient. dermatitis. mar/apr 2020;31(2):e17-e18. doi:10.1097/der.0000000000000560 4. jamgochian m, milgraum d, milgraum s, pappert a. dupilumab as treatment for atopic dermatitis in a pediatric heart transplant patient: a case report. dermatol ther. nov 2020;33(6):e14018. doi:10.1111/dth.14018 5. tsianakas a, ständer s. dupilumab: a milestone in the treatment of atopic dermatitis. lancet. jan 2 2016;387(10013):4-5. doi:10.1016/s01406736(15)00389-x 6. product approval information licensing action dupixent (dupilumab). available online at: https://www.accessdata.fda.gov/drugsatfda_docs /label/2017/761055lbl.pdf (accessed on 06 sep 2021). 7. marcus n, amir az, grunebaum e, et al. de novo allergy and immune-mediated disorders following solid-organ transplantationprevalence, natural history, and risk factors. j pediatr. may 2018;196:154-160.e2. doi:10.1016/j.jpeds.2017.11.026 powerpoint presentation comparison of ixekizumab and ustekinumab efficacy in the treatment of nail lesions of patients with moderate-to-severe plaque psoriasis: 52-week data from the ixora-s trial fall clinical dermatology conference 37th anniversary (fallcdc); las vegas, nv, usa; october 18-21, 2018 study was sponsored by eli lilly and company background  psoriasis is a chronic inflammatory disorder potentially affecting the skin, scalp, and nails1  up to 80% of patients with psoriasis have nail involvement1,2  nail psoriasis is persistent, slow to resolve, difficult to treat, and results can impair daily activities3-5  ixora-s is a phase 3b, multicenter trial that compared the efficacy of ixekizumab with ustekinumab in patients with moderate-to-severe psoriasis − ixekizumab demonstrated superior efficacy to ustekinumab in improving skin lesions up to week 526 and nail psoriasis up to week 247 objective  to evaluate the comparative efficacy of ixekizumab and ustekinumab in the treatment of nail psoriasis in patients with moderate-to-severe psoriasis in the headto-head ixora-s study at 52 weeks methods figure 1. study design: ixora-s conclusions  improvement in nail psoriasis lesions was observed in both treatment groups in ixora-s  complete resolution of nail psoriasis was seen in significantly greater percentages of patients treated with ixekizumab compared with ustekinumab from week 16 through week 52 of treatment  results suggest that ixekizumab provides significantly greater clearance of nail psoriasis than ustekinumab  longer periods of observation will be required to determine if nail lesions continue to improve beyond 52 weeks of treatment results significantly more ixekizumab-treated patients achieved pasi 90 and pasi 100 versus ustekinumab from week 4 through week 52 (primary endpoint),1 itt population, nri  inclusion criteria ⎼ ≥18-years-old ⎼ chronic plaque psoriasis for ≥6 months prior to baseline ⎼ failure, contraindication, or intolerance to ≥1 systemic therapya ⎼ psoriasis area and severity index (pasi) score ≥10 at screening and baseline  exclusion criteria ⎼ pattern of pustular, erythrodermic, and/or guttate forms of psoriasis ⎼ history of drug-induced psoriasis ⎼ received systemic non-biologic therapy or phototherapy for psoriasis <4 weeks before baseline, or have had topical psoriasis treatment <2 weeks before baseline ⎼ concurrent or recent useb of any biologic agent prior to baseline references 1. manhart r, rich p. clin exp rheumatol. 2015;33(suppl.93): s7-s13. 2. bardazzi f, et al. j eur acad dermatol venereol. 2017; 31:843-846. 3. reich a, szepietowski jc. am j clin dermatol. 2011;12:313-320. 4. gupta ak, cooper ea. j cutan med surg. 2009;13(suppl.2):s102-106. 5. tan es, et al. am j clin dermatol. 2012;13:375-388. 6. paul c, et al. j am acad dermatol. 2018;s0190-9622:32195-32199. 7. ghislain p-d, et al. eadv 26th congress. 2017;p1868. privacy notice regarding the collection of personal information by scanning this qr code, you are consenting to have your ip address and, if you choose, email address temporarily retained in a secured computer system and used only for counting purposes, performing file download, and sending you an email. your information will not be shared for any other purpose, unless required by law. you will not receive any future communications from eli lilly and company based on the system-retained information. contact information at: http://www.lilly.com/pages/contact.aspx disclosures  n. wasel has provided consultancy services for: abbott laboratories, amgen, astellas pharma, biogen idec, emd serono, isotechnika, janssen-ortho, ortho biotech, scheringplough, and wyeth, has performed contract research for: abbott laboratories, amgen, astellas pharma, biogen idec, celgene corp, centocor ortho biotech, eli lilly and company, emd serono, isotechnika, leo pharma, merck frosst, novartis pharmaceuticals, pfizer, takeda, and wyeth; y. dutronc is a current employee and stockholder of eli lilly and company; b. schinzel worked as a freelancer for clinipace worldwide to conduct the analysis of this study; j-p lacour has received grants from: abbvie, boehringer, celgene, eli lilly and company, janssen, leo pharma, novartis, and roche, has been a consultant for: abbvie, celgene, eli lilly and company, leo pharma, and novartis  lovisa berggren of clinipace worldwide provided statistical support for this presentation  this study was sponsored by eli lilly and company. medical writing services were provided by samantha forster, phd, of proscribe – part of the envision pharma group, and were funded by eli lilly and company baseline patient demographics and characteristics, itt population with baseline fingernail psoriasis norman wasel,1 yves dutronc,2 birgit schinzel,3 jean-philippe lacour4 1stratica medical and probity medical research, edmonton, canada; 2eli lilly and company, indianapolis, usa; 3clinipace worldwide, eschborn, germany; 4university hospital of nice, france ixe=ixekizumab; r=randomization; ust=ustekinumab aincluding cyclosporine, methotrexate, or phototherapy; bwithin the following washout periods: etanercept <28 days; infliximab, adalimumab, or alefacept <60 days; golimumab <90 days; rituximab <12 months; or any other biologic agent <5 half-lives prior to baseline statistical analyses  categorical data − logistic regression with terms for treatment, weight group (≤100 kg, >100 kg), and geographic region at week 52 • fisher’s exact test used as secondary analysis and at other visits • missing data imputed using non-responder imputation  continuous data − least squares mean change from baseline napsi and 95% confidence intervals for each treatment group compared using analysis of covariance with treatment, weight group (≤100 kg, >100 kg), geographic region, and baseline napsi score as factors • missing data imputed using baseline observation for patients who discontinued due to adverse events • last non-missing post-baseline observation carried forward used for patients discontinuing for other reasons (modified baseline observation carried forward)  improvement of psoriasis was observed in both treatment groups * p<.05 versus ust; † p≤.001 versus ust; ‡ p<.0001 versus ust based on fisher’s exact test itt=intent-to-treat; ixe q2w/q4w=ixekizumab 80 mg every 2 weeks to week 12 followed by ixekizumab 80 mg every 4 weeks; nri=non-responder imputation; pasi 90/100=at least 90%/100% improvement in psoriasis area and severity index; ust=45 mg ustekinumab for patients ≤100 kg and 90 mg ustekinumab for patients >100 kg at weeks 0 and 4 and every 12 weeks thereafter per label 1. paul c, et al. j am acad dermatol. 2018;s0190-9622:32195-32199. assessment of nail psoriasis  the nail psoriasis severity index (napsi) was used to assess fingernail psoriasis in patients with fingernail psoriasis at baseline  84 ixekizumab-treated (61.8%) and 105 ustekinumab-treated patients (63.3%) presented with fingernail psoriasis  baseline demographics and characteristics of patients were similar to those of patients in the itt population1 − no associations between treatment and age, gender, or weight found in patients with/without fingernail psoriasis at baseline itt=intent-to-treat; ixe q2w/q4w=ixekizumab 80 mg every 2 weeks to week 12 followed by ixekizumab 80 mg every 4 weeks; napsi=nail psoriasis severity index; ust=45 mg ustekinumab for patients ≤100 kg and 90 mg ustekinumab for patients >100 kg at weeks 0 and 4 and every 12 weeks thereafter per label 1. reich k, et al. br j dermatol. 2017;177:1014-1023. ust (n=105) ixe q2w/q4w (n=84) age, years 45.4 (12.7) 43.0 (12.0) male, n (%) 80 (76.2) 60 (71.4) weight, kg 91.3 (24.4) 87.5 (21.7) ≤100 kg, n (%) 71 (67.6) 62 (73.8) >100 kg, n (%) 34 (32.4) 22 (26.2) napsi total score median 1st quartile 3rd quartile 24.8 (20.0) 20.0 9.0 34.0 28.3 (19.9) 27.0 9.0 43.5 data are mean (standard deviation) unless otherwise specified baseline napsi score was not correlated with baseline pasi score, itt population with baseline fingernail psoriasis  no relationship between baseline napsi score and baseline pasi score was identified in either treatment group itt=intent-to-treat; ixe q2w/q4w=ixekizumab 80 mg every 2 weeks to week 12 followed by ixekizumab 80 mg every 4 weeks; napsi=nail psoriasis severity index; pasi=psoriasis area and severity index; ust=45 mg ustekinumab for patients ≤100 kg and 90 mg ustekinumab for patients >100 kg at weeks 0 and 4 and every 12 weeks thereafter per label napsi total score was significantly improved as early as week 16 for ixekizumab versus ustekinumab and was sustained through week 52, itt population with baseline fingernail psoriasis, observed * p<.05; † p≤.001; ‡ p<.0001 ixe versus ust based on anova with treatment, weight, geographic region, and baseline napsi score as factors anova=analysis of covariance; itt=intent-to-treat; ixe q2w/q4w=ixekizumab 80 mg every 2 weeks to week 12 followed by ixekizumab 80 mg every 4 weeks; napsi=nail psoriasis severity index; ust=45 mg ustekinumab for patients ≤100 kg and 90 mg ustekinumab for patients >100 kg at weeks 0 and 4 and every 12 weeks thereafter per label  improvement of nail psoriasis was observed in both treatment groups adjusted change from baseline in napsi total score was significantly greater as early as week 8 for ixekizumab versus ustekinumab and was sustained through week 52, itt population with baseline fingernail psoriasis, mbocf * p<.05; ‡ p<.0001 ixe versus ust based on anova with treatment, weight, geographic region, and baseline napsi score as factors anova=analysis of covariance; itt=intent-to-treat; ixe q2w/q4w=ixekizumab 80 mg every 2 weeks to week 12 followed by ixekizumab 80 mg every 4 weeks; lsm=least squares mean; mbocf; modified baseline observation carried forward; napsi=nail psoriasis severity index; ust=45 mg ustekinumab for patients ≤100 kg and 90 mg ustekinumab for patients >100 kg at weeks 0 and 4 and every 12 weeks thereafter per label  improvement from baseline of nail psoriasis was observed in both treatment groups significantly more ixekizumab-treated patients achieved complete resolution of nail psoriasis versus ustekinumab from week 16 through week 52, itt population with baseline fingernail psoriasis, nri  progressively more patients achieved complete resolution (napsi = 0) of nail psoriasis in both treatment groups * p<.05; † p≤.001; ‡ p<.0001 ixe versus ust based on fisher's exact test for treatment comparison itt=intent-to-treat; ixe q2w/q4w=ixekizumab 80 mg every 2 weeks to week 12 followed by ixekizumab 80 mg every 4 weeks; napsi=nail psoriasis severity index; nri=non-responder imputation; ust=45 mg ustekinumab for patients ≤100 kg and 90 mg ustekinumab for patients >100 kg at weeks 0 and 4 and every 12 weeks thereafter per label patients who achieve low pasi scores at week 52 may still experience significant nail involvement at week 52, itt population with baseline fingernail psoriasis itt=intent-to-treat; ixe q2w/q4w=ixekizumab 80 mg every 2 weeks to week 12 followed by ixekizumab 80 mg every 4 weeks; napsi=nail psoriasis severity index; pasi=psoriasis area and severity index; ust=45 mg ustekinumab for patients ≤100 kg and 90 mg ustekinumab for patients >100 kg at weeks 0 and 4 and every 12 weeks thereafter per label  most patients who have experienced nail improvement at week 52 have also obtained low pasi slide number 1 skin march 2018 volume 2 issue 2 copyright 2018 the national society for cutaneous medicine 127 in-depth reviews capsule commentaries: drug reaction considerations with oral minocycline james q. del rosso, do a,b,c a adjunct clinical professor (dermatology), touro university nevada, henderson, nv b research director, jdr dermatology research las vegas, nv c dermatology and cutaneous surgery, thomas dermatology, las vegas, nv oral minocycline is one of the most commonly prescribed antibiotics in dermatology, most frequently used for the treatment of acne vulgaris (av), but also utilized to treat cutaneous infections caused by a variety of organisms, such as staphylococcus aureus (including methicillin-resistant strains [mrsa]) and atypical mycobacterium spp. 1-4 minocycline is also a viable oral therapy option for the short-term treatment of papulopustular rosacea (ppr) in cases where oral doxycycline cannot be used, however, subantibiotic dosing with oral minocycline is not available; oral minocycline may also be used for the treatment of many cutaneous infections where doxycycline is used, such as staphylococcal infections, some mycobacterial infections, lyme disease, and selected rickettsial diseases. 3-6 in a case report of atypical mycobacterial infection (eg m marinum), oral minocycline was shown to be effective after failure with a 4-week course of oral doxycycline. 7 along with its successful use in many patients with non-infectious inflammatory dermatoses such as av, and for several types of cutaneous infections, oral minocycline, (like other tetracyclines) is associated with an overall favorable safety profile since its release into the marketplace in 1971. 2,8,9 nevertheless, oral minocycline may induce an array of potential side effects that are much more uncommon with or do not occur with other tetracycline agents. 2,9-16 this article highlights some uncommon but potentially serious adverse events (aes) that abstract minocycline is a commonly prescribed oral antibiotic in dermatology with a favorable efficacy and safety profile, and with clinical applications for a variety of cutaneous infections and other skin disorders. most patients do not experience any adverse events, although, rare but potentially serious side effects can emerge. in this article, drug hypersensitivity syndrome, hepatotoxicity, and pseudotumor cerebri associated with oral minocycline use are reviewed. introduction skin march 2018 volume 2 issue 2 copyright 2018 the national society for cutaneous medicine 128 may develop in association with the use of oral minocycline. some aes induced by oral minocycline may occur within days of initiation of therapy (eg vertigo/dizziness, urticaria), others within 2 weeks to a few months (eg drug hypersensitivity syndrome, serum sickness-like reaction (sslr]), and still others occur usually after prolonged therapy over several months to years (eg hyperpigmentation, autoimmune reactions). 2,10-14,16 drug hypersensitivity syndrome (dhs), also referred to as dress, is an uncommon ae that has been associated with certain drugs, such aromatic anticonvulsants (eg phenytoin), allopurinol, and minocycline, developing usually within 2 to 8 weeks after initiation of therapy. 2,10,11,14,17-19 affected patients often present with facial and peripheral edema, an exanthem, fatigue, fever, eosinophilia (in most cases), and a variety of systemic associations related to interstitial inflammation; hepatoxicity is seen in most cases, with other organ systems also affected in some cases (eg pneumonitis, nephritis, vasculitis, cerebritis, delayed-onset thyroiditis). 11,14,17 commentary: early recognition, discontinuation of the causative drug, prompt initiation of systemic corticosteroid therapy, and appropriate supportive care are strongly recommended. 17,19 in cases induced by minocycline, rechallenge with minocycline or other tetracyclines is not recommended due to the severity and morbidity associated with dhs (dress). 14 hepatitis associated with tetracycline agents is rare, including with doxycycline and minocycline. 2,10-12 in the case of minocycline, onset may be early, usually as a component of dhs, or after a prolonged duration of several months to years, most often as autoimmune hepatitis; the latter also presenting in some cases as part of minocycline-induced lupus-like syndrome (lls). 2,10,13-18,20,21 if hepatotoxicity associated with minocycline use is suspected or detected, it is important that the drug be discontinued immediately and both diagnostic efforts and management be initiated. 2,11,14,16,17,20 in cases of hepato toxicity with autoimmunity/lls associated with minocycline use, antinuclear antibody (ana) positivity is present, and other autoantibodies may also be detected in some cases. 2,16,17,20 many cases resolve upon drug discontinuation, however, some require immunosuppressive therapy. 16 commentary: awareness regarding potential hepatotoxicity, both of early onset or late onset, is important when prescribing oral minocycline. these reactions are rare, but must be kept in mind to optimize detection. although routine laboratory monitoring is not recommended with oral minocycline use, baseline ana and liver enzyme (eg transaminase) testing have been suggested when prolonged therapy with oral minocycline is anticipated (eg >1 year). 14 drug hypersensitivity syndrome (drug reaction with eosinophilia and systemic symptoms [dress]) hepatotoxicity skin march 2018 volume 2 issue 2 copyright 2018 the national society for cutaneous medicine 129 benign intracranial hypertension, commonly referred to as pseudotumor cerebri (ptc), is a relatively uncommon, but highly clinically significant potential adverse reaction associated with some medications. although disease states and not medications may be the cause of ptc in some cases, certain systemic drugs such as tetracyclines (eg tetracycline, minocycline, doxycycline), vitamin a, isotretinoin, and withdrawal from corticosteroids have been associated. 2,22,23 cases of ptc induced by minocycline have been reported, with onset within weeks of starting the drug, or after several months of use. 23-26 ptc often presents with severe/refractory cephalgia (often worsened with postural changes such as lying down, bending over), diplopia, photophobia, visual loss, transient visual changes, pulsatile tinnitus, nausea, and/or vomiting. 22,23 it is important to discontinue the suspected offending drug when ptc is suspected, and to arrange diagnostic examination by an ophthalmologist as immediately as possible; many cases resolve with prompt discontinuation of the causative agent (eg oral minocycline), although, prolonged visual changes/loss occurs in some cases. 22-26 among the tetracyclines, the relative incidence is 4,400/100,000/year with minocycline and 110/100,000/year with doxycycline. 23 commentary: it is important to maintain a high index of suspicion for ptc in a patient using an oral tetracycline if there is emergence of refractory headaches, symptoms that affect their vision, and pulsatile tinnitus. the risk of ptc appears to be higher with oral minocycline. if symptoms suggestive of ptc develop in a patient taking a tetracycline agent such as minocycline, immediately have the patient stop the drug and promptly arrange for consultation with an ophthalmologist. oral minocycline is a very commonly prescribed antibiotic in dermatology due to a favorable efficacy and safety profile, and a broad range of clinical applications for a variety of infections and other cutaneous disorders. most patients do not experience significant side effects, although, rare but potentially serious adverse events can occur. this article reviews some of these rare side effects that may be induced by minocycline to assist clinicians in prompt recognition and appropriate management. conflict of interest disclosures: dr. del rosso is a consultant, investigator, and/or speaker for allergan, aqua/almirall, bayer, biopharmx, celgene, cipher (innocutis), cutanea, dermira, ferndale, foamix, galderma, genentech, innovaderm, leopharma, novan, novartis, pfizer (anacor), pharmaderm, promius, regeneron, sanofi/genzyme, sebacia, sunpharma, taro, unilever, ortho dermatologics (valeant), and viamet. this article was developed and written solely by the author. the author did not receive any form of compensation, either directly or indirectly, from any company or agency related to the development, authorship, or publication of this article. funding: none. corresponding author: james q. del rosso, do jdr dermatology research 9080 west post road suite 100 las vegas, nevada 89148 702-331-4123 jqdelrosso@yahoo.com benign intracranial hypertension (pseudotumor cerebri) summary skin march 2018 volume 2 issue 2 copyright 2018 the national society for cutaneous medicine 130 references: 1. del rosso jq, webster gf, rosen t, et al. status report from the scientific panel on antibiotic use in dermatology of the american acne and rosacea society part 1: antibiotic prescribing patterns, sources of antibiotic exposure, antibiotic consumption and emergence of antibiotic resistance, impact of alterations in antibiotic prescribing, and clinical sequelae of antibiotic use. j clin aesthet dermatol. 2016;9(4):18–24. 2. kim s, michaels bd. kim gk, del rosso jq. systemic antibacterial agents. in: wolverton se, ed, comprehensive dermatologic drug therapy, 3rd edition, elsevier-saunders, philadelphia, pennsylvania, 2013, pp 61-98. 3. garrido-mesa n, zarzuelo a, galvez j. minocycline: far beyond an antibiotic. br j pharmacol. 2013;169(2):337-352. 4. vaneperen as, segreti j. empirical therapy in methicillin-resistant staphylococcus aureus infections: an up-to-date approach. j infect chemother. 2016;22(6):351-359. 5. van der linden mmd, van ratingen ar, van rappard dc, et al. domino, doxycycline 40 mg vs. minocycline 100 mg in the treatment of rosacea: a randomized, single-blinded, noninferiority trial, comparing efficacy and safety. br j dermatol. 2017;176(6):1465-1474. 6. carris nw, pardo j, montero j, et al. minocycline as a substitute for doxycycline in targeted scenarios: a systematic review. open forum infect dis. 2015 nov 25;2(4):178. doi: 10.1093/ofid/ofv178. ecollection 2015 dec. 7. cummins dl, delacerda d, tausk fa. mycobacterium marinum with different responses to second-generation tetracyclines. int j dermatol. 2005;44(6):518-520. 8. leyden jj, del rosso jq. oral antibiotic therapy for acne vulgaris: pharmacokinetic and pharmacodynamic perspectives. j clin aesthet dermatol. 2011;4(2):40-47. 9. del rosso jq. topical and oral antibiotics for acne vulgaris. semin cutan med surg. 2016;35(2):57-61. 10. kircik l. doxycycline and minocycline for the management of acne: a review of efficacy and safety with emphasis on clinical implications. j drugs dermatol. 2010;9(11):1407-1411. 11. shapiro le, knowles sr, shear nh. comparative safety of tetracycline, minocycline, and doxycycline. arch dermatol. 1997;133(10):1224-1130. 12. del rosso jq. oral antibiotics. in: shalita ar, del rosso jq, webster gf, eds, acne vulgaris, informa healthcare, london, united kingdom, 2011, pp 113-124. skin march 2018 volume 2 issue 2 copyright 2018 the national society for cutaneous medicine 131 13. somech, arav-boger r. assia a, et al. complications of minocycline therapy for acne vulgaris: case reports and review of the literature. pediatr dermatol. 1999;16(6):469-472. 14. knowles sr, shapiro l, shear nh. serious adverse reactions induced by minocycline. report of 13 patients and review of the literature. arch dermatol. 1996;132(8):934-939. 15. garner se, eady ea, bennett c. minocycline for acne vulgaris: efficacy and safety. cochrane database syst rev. 2012 aug 15;(8):cd002086. doi: 10.1002/14651858.cd002086.pub2. 16. teitelbaum je, perez-atayde ar, cohen m, et al. minocycline-related autoimmune hepatitis: case series and literature review. arch pediatr adolesc med. 1998;152(11):1132-1136. 17. knowles sr, shear nh. cutaneous drug reactions with systemic features. in: wolverton se, ed, comprehensive dermatologic drug therapy, 3rd edition, elsevier-saunders, philadelphia, pennsylvania, 2013, pp 747-752. 18. fleming p, marik pe. the dress syndrome: the great clinical mimicker. pharmacotherapy. 2011;31(3):332. 19. oelze ll1, pillow mt. phenytoininduced drug reaction with eosinophilia and systemic symptoms (dress) syndrome: a case report from the emergency department. j emerg med. 2013 jan;44(1):75-78. 20. ramakrishna j, johnson ar, banner bf. long-term minocycline use for acne in healthy adolescents can cause severe autoimmune hepatitis. j clin gastroenterol. 2009;43(8):787-790. 21. margolis dj, hoffstad o, bilker w. association or lack of association between tetracycline class antibiotics used for acne vulgaris and lupus erythematosus. br j dermatol. 2007;157(3):540-546. 22. friedman di. medication-induced intracranial hypertension in dermatology. am j clin dermatol. 2005;6(1):29-37. 23. passi sf, butcher r, warner jea, et al. incidence of idiopathic intracranial hypertension (iih) among users on tetracycline antibiotics. san diego ca: north american neuro-ophthalmology society meeting; february 21-26, 2015. 24. chiu am, chuenkongkaew wl, cornblath wt, et al. minocycline treatment and pseudotumor cerebri. am j ophthalmol. 1998;126(1):116121. 25. bababeygy sr, repka mx, subramanian ps. minocyclineassociated pseudotumor cerebri with severe papilledema. j ophthalmol. 2009;2009:203583. 26. mochizuki k, takahashi t, kano m, et al. pseudotumor cerebri induced by minocycline for acne vulgaris. jpn j ophthalmol. 2002;46(6):668-672. leo1825a_wollenberg4x4-v2 risk of anaphylaxis and conjunctivitis with tralokinumab in atopic dermatitis andreas wollenberg,1 emma guttman-yassky,2 mathias torpet,3 jonathan i silverberg4 1department of dermatology and allergy, ludwig maximilian university, munich, germany; 2department of dermatology and the laboratory for inflammatory skin diseases, icahn school of medicine at mount sinai, new york, ny, usa; 3leo pharma a /s, ballerup, denmark; 4departments of dermatology, preventive medicine, and medical social sciences, feinberg school of medicine, northwestern university, chicago, il, usa objectives • to evaluate the risk of developing adas with tralokinumab treatment in the phase 2b study. • to investigate reports of anaphylaxis, or other severe hypersensitivity reactions, and compare the incidence of eye disorders, including conjunctivitis, between the placebo and tralokinumab treatment groups. methods study design • patients were randomised 1:1:1:1 to receive subcutaneous tralokinumab (45 mg, 150 mg or 300 mg) or placebo every 2 weeks for 12 weeks on a tcs background (figure 1). • concomitant class 3 (world health organisation) tcs were administered at least once daily during the 2-week run-in and as needed throughout the treatment and follow-up periods. patients • 8) and with ad body surface area involvement of 10%, easi score of 12, scorad of 25 and iga of 3. • key exclusion criteria included: active dermatological conditions that may confound ad diagnosis, allergic or irritant contact dermatitis and history of anaphylaxis following any biologic therapy. measurement of anti-drug antibodies • adas were measured using a validated electrochemiluminescence method (meso scale discovery sector imager 6000). samples for ada response were taken at day 1 (prior to treatment) and weeks 4, 12 and 22. capture of anaphylaxis/serious hypersensitivity reactions • aes associated with anaphylaxis/serious hypersensitivity were captured using the following standardised medical dictionary for regulatory activities queries: hypersensitivity, anaphylactic reaction and anaphylactic/anaphylactoid shock conditions.9 eye disorders • eye disorders, including but not limited to conjunctivitis, were extracted from the aes occurring during treatment for all subjects in each treatment arm: placebo: n=51, tralokinumab 45 mg: n=50, tralokinumab 150 mg: n=51 and tralokinumab 300 mg: n=52. — all events were included regardless of seriousness, causality or any other parameter of the aes. • cases of eye disorders were compared between placebo and tralokinumab arms. statistical analysis • safety data were summarised descriptively according to the highest dosage received by each participant measured in the as-treated population. results patient characteristics • overall, 204 patients were randomised in the phase 2b study and included in the as-treated population: 153 tralokinumab-treated patients and 51 placebo-treated patients. • baseline demographics and disease characteristics were similar between treatment groups.7 anti-drug antibodies • three patients in the tralokinumab 45-mg group had pre-existing adas at baseline. these are likely to be the result of the ‘cut point’ for the ada assay, which is typically set expecting some positive results. • only one tralokinumab-treated patient (300-mg group) had ada formation, which was measured at week 22. the titre was low and had no impact on the observed pharmacokinetics of tralokinumab. — no aes were reported for this patient. • anaphylaxis/severe hypersensitivity reactions • eye disorders • or all eye disorders between the placebo and pooled tralokinumab groups (figure 2). — no dose-related trend was observed, as the greatest frequency of one or more eye disorders was reported for the tralokinumab 150-mg treatment group. introduction • biologics, including human monoclonal antibodies (mabs), are currently diseases such as psoriasis1 and atopic dermatitis (ad).2 • potential safety concerns regarding the immunogenicity of biologics remain, including development of anti-drug antibodies (adas) and adverse events (aes) such as anaphylaxis and/or severe hypersensitivity reactions.3 • conjunctivitis with treatment, as aes of conjunctivitis were more frequently reported in patients treated with biologics targeting interleukin (il)-13 and il-4.4,5 • tralokinumab is an igg 4 6 and has been evaluated in a phase 2b, randomised, double-blind, placebo-controlled study (nct02347176) in adults with moderate to severe ad. — results of the study showed improvements in the eczema area and severity index (easi), investigator’s global assessment (iga) and scoring atopic dermatitis (scorad) scores with tralokinumab on a background of topical corticosteroids (tcs), with a favourable overall safety and 7 figure 1. study design weeks –6 –2 0 12 22 follow-up period primary endpoint treatment period run-in period screening period tralokinumab 300 mg sc q2w + tcs (n=52) tralokinumab 150 mg sc q2w + tcs (n=51) tralokinumab 45 mg sc q2w + tcs (n=50) patients with moderate to severe ad tcs tcs placebo sc q2w + tcs (n=51) ad, atopic dermatitis; q2w, every 2 weeks; sc, subcutaneous; tcs, topical corticosteroids. 27th eadv congress, 12−16 september 2018, paris, france objectives methods introduction conclusions references 1. kotsovilis s, andreakos e. methods mol biol 2014; 1060: 37–59. 2. seegraber m et al. expert rev clin pharmacol 2018; 11: 467–474. 3. vultaggio a et al. curr treat options allergy 2016; 3: 147–157. 4. wollenberg a et al. j allergy clin immunol pract 2018; pii: s2213-2198(18)30089-8. doi: 10.1016/j.jaip.2018.01.034. [epub ahead of print]. 5. simpson el et al. j am acad dermatol 2018; 78: 863–871. 6. popovic b et al. j mol biol 2017; 429: 208–219. 7. wollenberg a et al. j allergy clin immunol 2018; pii: s0091-6749(18)30850-9. doi: 10.1016/j.jaci.2018.05.029. [epub ahead of print]. 8. 9. medra medical dictionary for regulatory activities. 2018. acknowledgements the tralokinumab phase 2b study was sponsored by medimmune. this poster was sponsored by leo pharma. medical writing and editorial support was provided by stephanie rippon and jane beck from complete healthvizion, funded by leo pharma. figure 1. study design weeks –6 –2 0 12 22 follow-up period primary endpoint treatment period run-in period screening period tralokinumab 300 mg sc q2w + tcs (n=52) tralokinumab 150 mg sc q2w + tcs (n=51) tralokinumab 45 mg sc q2w + tcs (n=50) patients with moderate to severe ad tcs tcs placebo sc q2w + tcs (n=51) ad, atopic dermatitis; q2w, every 2 weeks; sc, subcutaneous; tcs, topical corticosteroids. fall clinical dermatology conference, october 18-21, 2018, las vegas, nv figure 2. frequency of patients with one or more eye disorders in the placebo and pooled tralokinumab treatment groups 4 3 conjunctivitis 1 keratitis 6 7 all eye disorders f re q u en cy ( % ) 14 12 10 8 6 4 2 0 eye disorder placebo (n=51) pooled tralokinumab (n=153) table 1. incidence of eye disorders (including conjunctivitis) for placebo and tralokinumab treatment groups tralokinumab frequency of eye disorder events, n (%) placebo (n=51) 45 mg (n=50) 150 mg (n=51) 300 mg (n=52) pooled (n=153) conjunctivitis 2 (4) 1 (2) 3 (6)† 0 4 (3) allergic conjunctivitis 0 0 1 (2)† 0 1 (1) episcleritis 0 0 1 (2)† 0 1 (1) eye infection 1 (2)* 0 1 (2)‡ 0 1 (1) eye pruritus 0 1 (2) 0 0 1 (1) eye swelling 0 0 1 (2)† 0 1 (1) herpes ophthalmic 0 1 (2) 0 0 1 (1) hordeolum 0 0 1 (2)† 0 1 (1) iridocyclitis 1 (2)* 0 0 0 0 keratitis 0 0 1 (2) 0 1 (1) increased lacrimation 0 0 1 (2)† 0 1 (1) macular edema 0 0 1 (2)† 0 1 (1) periorbital rash 0 0 1 (2)† 0 1 (1) patients with 1 eye event, n (%) 3 (6) 3 (6) 7 (14) 0 10 (7) *eye infection and iridocyclitis were reported by the same patient in the placebo group. †three patients in the tralokinumab 150-mg group reported 1 event: 1) episcleritis and hordeolum; 2) conjunctivitis and macular edema; and 3) periorbital rash, eye swelling, increased lacrimation and allergic conjunctivitis. ‡staphylococcal eye infection. • biologics, including human monoclonal antibodies (mabs), are currently approved for the therapy of numerous diseases, including inflammatory skin diseases such as psoriasis1 and atopic dermatitis (ad).2 • potential safety concerns regarding the immunogenicity of biologics remain, including development of anti-drug antibodies (adas) and adverse events (aes) such as anaphylaxis and/or severe hypersensitivity reactions.3 • a specific concern for the use of biologics in ad is the possibility of unexplained conjunctivitis with treatment, as aes of conjunctivitis were more frequently reported in patients treated with biologics targeting interleukin (il)-13 and il-4.4,5 • tralokinumab is an igg 4 fully human mab that works by specifically blocking the effects of il-136 and has been evaluated in a phase 2b, randomised, double-blind, placebo-controlled study (nct02347176) in adults with moderate to severe ad. — results of the study showed improvements in the eczema area and severity index (easi), investigator’s global assessment (iga) and scoring atopic dermatitis (scorad) scores with tralokinumab on a background of topical corticosteroids (tcs), with a favourable overall safety and tolerability profile.7 objectives • to evaluate the risk of developing adas with tralokinumab treatment in the phase 2b study. • to investigate reports of anaphylaxis, or other severe hypersensitivity reactions, and compare the incidence of eye disorders, including conjunctivitis, between the placebo and tralokinumab treatment groups. methods study design • patients were randomised 1:1:1:1 to receive subcutaneous tralokinumab (45 mg, 150 mg or 300 mg) or placebo every 2 weeks for 12 weeks on a tcs background (figure 1). • concomitant class 3 (world health organisation) tcs were administered at least once daily during the 2-week run-in and as needed throughout the treatment and follow-up periods. patients • eligible patients were aged 18–75 years with physician-confirmed diagnosis of ad for >1 year (according to hanifin and rajka criteria8) and with ad body surface area involvement of >10%, easi score of >12, scorad of >25 and iga of >3. • key exclusion criteria included: active dermatological conditions that may confound ad diagnosis, allergic or irritant contact dermatitis and history of anaphylaxis following any biologic therapy. measurement of anti-drug antibodies • adas were measured using a validated electrochemiluminescence method (meso scale discovery sector imager 6000). samples for ada response were taken at day 1 (prior to treatment) and weeks 4, 12 and 22. capture of anaphylaxis/serious hypersensitivity reactions • aes associated with anaphylaxis/serious hypersensitivity were captured using the following standardised medical dictionary for regulatory activities queries: hypersensitivity, anaphylactic reaction and anaphylactic/anaphylactoid shock conditions.9 eye disorders • eye disorders, including but not limited to conjunctivitis, were extracted from the aes occurring during treatment for all subjects in each treatment arm: placebo: n=51, tralokinumab 45 mg: n=50, tralokinumab 150 mg: n=51 and tralokinumab 300 mg: n=52. —all events were included regardless of seriousness, causality or any other parameter of the aes. • cases of eye disorders were compared between placebo and tralokinumab arms. statistical analysis • safety data were summarised descriptively according to the highest dosage received by each participant measured in the as-treated population. results patient characteristics • overall, 204 patients were randomised in the phase 2b study and included in the as-treated population: 153 tralokinumab-treated patients and 51 placebo-treated patients. • baseline demographics and disease characteristics were similar between treatment groups.7 anti-drug antibodies • three patients in the tralokinumab 45-mg group had pre-existing adas at baseline. these are likely to be the result of the ‘cut point’ for the ada assay, which is typically set expecting some positive results. • only one tralokinumab-treated patient (300-mg group) had ada formation, which was measured at week 22. the titre was low and had no impact on the observed pharmacokinetics of tralokinumab. — no aes were reported for this patient. • no positive cases of adas were identified in the placebo group. anaphylaxis/severe hypersensitivity reactions • no cases of anaphylasxis or severe hypersensitivity were identified in this study. eye disorders • overall, there was no difference in the frequency of patients reporting conjunctivitis, keratitis or all eye disorders between the placebo and pooled tralokinumab groups (figure 2). — no dose-related trend was observed, as the greatest frequency of one or more eye disorders was reported for the tralokinumab 150-mg treatment group. • the number of patients with >1 eye disorder was 6%, 6%, 14% and 0% in the placebo and tralokinumab 45-mg, 150-mg and 300-mg treatment groups, respectively, and 7% in the pooled tralokinumab group (table 1). • four patients experienced more than one eye event: — eye infection and iridocyclitis were reported by the same patient in the placebo group. — in the tralokinumab 150-mg group, three patients reported more than one eye event. two patients each reported two events: episcleritis and hordeolum, and conjunctivitis and macular edema. a third patient reported four events: periorbital rash, eye swelling, increased lacrimation and allergic conjunctivitis. • no events of blepharitis were reported. events of conjunctivitis and keratitis were infrequent: event rates were 4%, 2%, 6% and 0% for conjunctivitis in the placebo and tralokinumab 45-mg, 150-mg and 300-mg groups, respectively, and were 2% for keratitis in the tralokinumab 150-mg group. • all eye disorders were non-serious, mild or moderate in severity and reported as not related to treatment. • two patients discontinued treatment due to eye disorders: one patient in the placebo group (iridocyclitis) and one patient in the tralokinumab 150-mg group (keratitis). limitations • hypersensitivity reactions are rare; therefore, they are not expected to be observed in such a small sample. • conjunctivitis was not pre-defined as an ae of special interest in the phase 2b study • due to small numbers of patients in the treatment groups and low incidences of eye disorders, between-group statistical comparisons were not performed. • no safety concerns were identified for tralokinumab on background of tcs in this phase 2b study in patients with moderate to severe ad with respect to ada development or anaphylaxis/hypersensitivity. • no difference in the incidence of conjunctivitis or eye disorders was observed between the placebo and pooled tralokinumab groups in this study. — conjunctivitis was infrequently reported, with no incidences considered to be study drug related.7 • there was no apparent dose response in the frequency of eye disorder events. the second-largest frequency was observed in the placebo group, while the largest frequency was seen in the tralokinumab 150-mg group, compared to zero events in the tralokinumab 300-mg group. • the safety (and efficacy) profile of tralokinumab 300 mg is currently being further investigated in large phase 3 studies as monotherapy (nct03131648 and nct03160885) and in combination with tcs (nct03363854) in adults with moderate to severe ad. glp-00068950_baseline a1c poster layout an update on the long-term safety experience of ixekizumab: results from the psoriasis clinical development program with more than 3 years of follow-up from 12 clinical trials and more than 15000 patient-years of exposure to ixekizumab april armstrong,1 noah agada,2 wen xu,2 gaia gallo2 1department of clinical research, keck school of medicine of the university of southern california, los angeles, usa; 2eli lilly and company, indianapolis, usa disclosures  a. armstrong has served as investigator, advisor, and/or speaker for: abbvie, celgene, eli lilly and company, janssen, novartis, regeneron, sanofi, and valeant; n. agada, w. xu, and g. gallo are current employees and shareholders of eli lilly and company  this study was sponsored by eli lilly and company. medical writing assistance was provided by cassandra haley, phd, cmpp, of proscribe – part of the envision pharma group, and was funded by eli lilly and company overview of adverse events privacy notice regarding the collection of personal information by scanning this qr code, you are consenting to have your ip address and, if you choose, email address temporarily retained in a secured computer system and used only for counting purposes, performing file download, and sending you an email. your information will not be shared for any other purpose, unless required by law. you will not receive any future communications from eli lilly and company based on the system-retained information. contact information at: http://www.lilly.com/pages/contact.aspx ainflammatory bowel disease events were defined by narrow terms incidence rates of safety topics of special interest study was sponsored by eli lilly and company n (ir) [95% ci] all pso ixe (n=5871)py=15,212.5 serious infection 203 (1.3) [1.2, 1.5] oral candida 144 (0.9) [0.8, 1.1] mace 76 (0.5) [0.4, 0.6] non-melanoma skin cancer (nmsc) 47 (0.3) [0.2, 0.4] malignancies excluding nmsc 78 (0.5) [0.4, 0.6] inflammatory bowel disease (ibd)a 23 (0.2) [0.1, 0.2] crohn’s disease 6 (0.0) [0.0, 0.1] ulcerative colitis 16 (0.1) [0.1, 0.2] ibd preferred term 1 (0.0) [0.0, 0.0] n (ir) [95% ci] all pso ixe (n=5871)py=15,212.5 ≥1 teaea 5072 (33.3) [32.4, 34.3] mild 1389 (9.1) [8.7, 9.6] moderate 2770 (18.2) [17.5, 18.9] severe 912 (6.0) [5.6, 6.4] ≥1 sae 854 (5.6) [5.2, 6.0] deaths 32 (0.2) [0.1, 0.3] discontinuations due to adverse event 432 (2.8) [2.6, 3.1] patients with multiple occurrences of the same event were categorized by the highest severity aseverity data were missing for 1 patient ■ most common teaes (ir [95% confidence interval; ci] per 100 py) were upper respiratory tract infections (viral: 9.9 [9.4, 10.4]; unspecified: 5.8 [5.5, 6.2]) and injection site-reactions (3.7 [3.5, 4.1]), which were generally mild or moderate in severity ■ most deaths were from cardiovascular events in patients with prior risk factors, and none were due to suicide ■ in moderate-to-severe psoriasis, maintaining adequate control of disease activity generally requires long-term treatment1-4 ■ ixekizumab is a high-affinity monoclonal antibody that selectively targets interleukin (il)-17a5 – has demonstrated significant efficacy in the treatment of moderateto-severe psoriasis6-9 – is approved for treating moderate-to-severe plaque psoriasis – safety profile is aligned with il-17a inhibition and similar to that of etanercept in the short-term (uncover-2 and -3)8,9 background ■ to summarize integrated safety data based on more than 15,000 patient-years (py) of ixekizumab exposure during 12 clinical trials in patients with psoriasis objective references 1. jacobs a, et al. br j dermatol. 2015;173:910-921. 2. mease pj, et al. drugs. 2014;74:423-441. 3. mrowietz u, et al. j eur acad dermatol venereol. 2012;26(suppl.2):12-20. 4. sandoval lf, et al. am j clin dermatol. 2014;15:165-180. 5. liu l, et al. j inflamm res. 2016;9:39-50. 6. leonardi c, et al. n eng j med. 2012;366:1190-1199. 7. gordon kb, et al. j am acad dermatol. 2014;71:1176-1182. 8. griffiths ce, et al. lancet. 2015;386:541-551. 9. gordon kb, et al. n eng j med. 2016;375:345-356. treatment-emergent adverse event (teae) data were integrated from 12 controlled and uncontrolled ixekizumab clinical trials in psoriasis, including 3 pivotal phase 3, randomized, controlled, double-blind clinical trials (uncover-1, -2, and -3) ■ safety analysis population included all randomized patients who received ≥1 dose of study drug ■ data cut-off date was september 22, 2017 ■ exposure-adjusted incidence rates (irs) of teaes were summarized ■ ir was expressed as the number of unique patients with a given category of teae per 100 py, based on the entire duration of exposure ■ categories included overall teaes, infections, injection-site reactions, allergic reactions/hypersensitivities, and malignancies ■ summary data from the induction period (12 weeks) of uncover-1, -2, and -3 are provided for reference ■ data for ixekizumab doses were grouped to form the total ixe group ■ summary data from the 2 previous database locks (september 2015 including 7 psoriasis clinical trials and september 2016 including 11 psoriasis clinical trials) are also included for reference ■ safety topics of special interest included serious infections, oral candida, major adverse cerebro-cardiovascular events (mace), non-melanoma skin cancer (nmsc), malignancies excluding nmsc, and inflammatory bowel disease (including crohn’s disease and ulcerative colitis) ■ mace were adjudicated by an external adjudication committee methods integrated psoriasis safety dataset study design air per 100 py considered exposure time as the entire time on ixe; bdata for the induction period (0-12 weeks) are provided for reference and display the ir for 0-12 weeks for uncover-1, -2, and -3 only; data for year 1 and year 2 are also provided for reference and display ir for the 2 previous database locks (september 2015 including 7 pso clinical trials and september 2016 including 11 pso clinical trials) i n d u c t i o n p e r i o d b 0 1 2 w e e k s y e a r 1 s e p t 2 0 1 5 y e a r 2 s e p t 2 0 1 6 y e a r 3 s e p t 2 0 1 7 0 5 0 1 0 0 1 5 0 2 0 0 2 5 0 3 0 0 w e e k 2 4 ir p e r 1 0 0 p y a (9 5 % c i) a ll ix e p s ot o ta l ix e i n f e c t i o n s p b o n = 7 9 1 2 3 2 8 4 2 1 3 5 6 8 9 5 8 7 1 p y = 1 8 0 5 3 5 7 8 4 3 1 2 ,0 6 2 1 5 ,2 1 3 1 0 1 1 1 8 3 4 2 9 2 5 i n d u c t i o n p e r i o d b 0 1 2 w e e k s y e a r 1 s e p t 2 0 1 5 y e a r 2 s e p t 2 0 1 6 y e a r 3 s e p t 2 0 1 7 0 5 0 1 0 0 1 5 0 2 0 0 2 5 0 3 0 0 w e e k 2 4 ir p e r 1 0 0 p y a (9 5 % c i) a ll ix e p s ot o ta l ix e i n j e c t i o n s it e r e a c t io n s p b o n = 7 9 1 2 3 2 8 4 2 1 3 5 6 8 9 5 8 7 1 p y = 1 8 0 5 3 5 7 8 4 3 1 2 ,0 6 2 1 5 ,2 1 3 1 4 6 5 9 7 6 i n d u c t i o n p e r i o d b 0 1 2 w e e k s y e a r 1 s e p t 2 0 1 5 y e a r 2 s e p t 2 0 1 6 y e a r 3 s e p t 2 0 1 7 0 5 0 1 0 0 1 5 0 2 0 0 2 5 0 3 0 0 w e e k 2 4 ir p e r 1 0 0 p y a (9 5 % c i) a ll ix e p s ot o ta l ix e a ll e r g ic r e a c t i o n s / h y p e r s e n s i t i v i t ie s p b o n = 7 9 1 2 3 2 8 4 2 1 3 5 6 8 9 5 8 7 1 p y = 1 8 0 5 3 5 7 8 4 3 1 2 ,0 6 2 1 5 ,2 1 3 8 1 5 7 6 6 i n d u c t i o n p e r i o d b 0 1 2 w e e k s y e a r 1 s e p t 2 0 1 5 y e a r 2 s e p t 2 0 1 6 y e a r 3 s e p t 2 0 1 7 0 5 0 1 0 0 1 5 0 2 0 0 2 5 0 3 0 0 w e e k 2 4 ir p e r 1 0 0 p y a (9 5 % c i) a ll ix e p s ot o ta l ix e m a l i g n a n c i e s p b o n = 7 9 1 2 3 2 8 4 2 1 3 5 6 8 9 5 8 7 1 p y = 1 8 0 5 3 5 7 8 4 3 1 2 ,0 6 2 1 5 ,2 1 3 1 1 1 11 incidence rates of select teaes decreased or remained similar through year 3 databasekey results duration of ixekizumab exposure n (%) all pso ixe (n=5871)py=15,212.5 ≥1 week 5866 (99.9) ≥1 month 5806 (98.9) ≥3 months 5665 (96.5) ≥0.5 years 5455 (92.9) ≥1 year 4640 (79.0) ≥1.5 years 3357 (57.2) ≥2 years 3201 (54.5) ≥3 years 2891 (50.8) ≥4 years 1526 (26.0) ≥5 years 261 (4.4) incidence rates of overall teaes decreased or remained similar through year 3 database air per 100 py considered exposure time as the entire time on ixe bdata for the induction period (0-12 weeks) are provided for reference and display the ir for 012 weeks for uncover-1, -2, and -3 only; data for year 1 and year 2 are also provided for reference and display ir for the 2 previous database locks (september 2015 including 7 pso clinical trials and september 2016 including 11 pso clinical trials) i n d u c t i o n p e r i o d b 0 1 2 w e e k s y e a r 1 s e p t 2 0 1 5 y e a r 2 s e p t 2 0 1 6 y e a r 3 s e p t 2 0 1 7 0 5 0 1 0 0 1 5 0 2 0 0 2 5 0 3 0 0 w e e k 2 4 ir p e r 1 0 0 p y a (9 5 % c i) a ll ix e p s ot o ta l ix ep b o n = 7 9 1 2 3 2 8 4 2 1 3 5 6 8 9 5 8 7 1 p y = 1 8 0 5 3 5 7 8 4 3 1 2 ,0 6 2 1 5 ,2 1 3 2 0 6 2 5 6 4 6 4 0 3 3 abbreviations ac=active comparator; ci=confidence interval; db=double-blind; ep=optional extension period after week 24 endpoint where patients received 80 mg ixe q4w up to wk 60; etn=50 mg etanercept twice weekly; fae=fumaric acid esters 105-mg starting dose followed by 215 mg given orally 1 to 3 times per day; ir=incidence rate; ixe=ixekizumab; ixe q2w=80 mg ixekizumab every 2 weeks; ixe q4w=80 mg ixekizumab every 4 weeks; ixe q12w=80 mg ixekizumab every 12 weeks; lte=long-term extension; mace=major adverse cerebro-cardiovascular events; mtx=methotrexate 7.5-mg starting dose up to 30 mg given orally once a week; n=number of patients; n=number of patients who received ixekizumab and included in the september 2017 lock for integrated safety analyses; ol=open-label; pac=placebo-controlled and active comparator; pbo=placebo; pso=psoriasis; pts=patients; py=patient-years; r=randomized; sae=serious adverse event; spga=static physician’s global assessment; teae=treatment-emergent adverse event; ust=45 mg ustekinumab given as sc injection for participants ≤100 kg and 90 mg sc injection for participants >100 kg at wk 0, 4, 16, 28, and 40; wk=week ■ the ixekizumab psoriasis clinical safety database is large with more than 15,000 py from 12 clinical trials and up to 5 years of study duration ■ no new safety signals were identified with longer-term ixekizumab treatment in this population of patients with moderate-to-severe plaque psoriasis ■ ixekizumab exposure of up to greater than 3 years was not associated with an increased rate of any type or category of teae conclusions afor pts receiving ixe the starting dose was 160 mg at wk 0 prior to receiving 80 mg ixe (q4w or q2w); bwithdrawal period (wks 20-32; pts were eligible for treatment with ixe q4w when improvement in pasi score from baseline was ≤75%); cprotocol amendment-mandated dose regimen; dpbo administered to maintain study blind; estep-up criteria determined if dosing increased from ixe q4w to ixe q2w based on whether a patient achieved spga ≥2 at 2 consecutive visits during wk 12 through wk 40; fdosing increased from ixe q4w to ixe q2w based on investigator opinion between wk 24 through wk 40 fall clinical dermatology conference 37th anniversary (fallcdc); las vegas, nv, usa; october 18-21, 2018 an update on the long-term safety experience of ixekizumab: results from the psoriasis clinical development program with more than 3 years of follow-up from 12 clinical trials and more than 15000 patient-years of exposure to ixekizumab skin july 2021 1227 proof returned skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 422 brief article angiosarcoma clinically mimicking a targetoid hemosiderotic hemangioma hannah nam, ba1, jordan lim, mb bch bao1, alexandra flamm, md1 1penn state health, hershey medical center, department of dermatology, hershey, pa angiosarcoma is a rare, aggressive softtissue sarcoma of endothelial cell origin with increased likelihood for local recurrence, metastasis, and poor prognosis. angiosarcomas can affect any organ in the body; however, nearly 50% of all cases are of its cutaneous form often of the head and neck1. the five year survival of cutaneous angiosarcoma ranges from 10-30%2. the variation in clinical presentation and the lack of disease awareness contribute to the difficulty in diagnosis3; however, early detection and intervention is critical for improved prognosis. the size of lesion at presentation is an important prognostic factor for cutaneous angiosarcoma3, and a delayed diagnosis may lead to substantial challenges in treatment4. perez et al. reported that a tumor size less than 5cm was associated with a significantly improved overall and recurrence-free survival compared to a tumor size greater than 5cm5. despite early detection, the neoplasm can often be more advanced than is apparent from initial physical exam2. this case report emphasizes the value of early clinical suspicion for atypical, rapidly changing vascular lesions. a 69-year-old white man with no history of skin cancer presented with a 2cm vascular targetoid lesion with a central 5mm firm dermal purple nodule and surrounding ecchymosis on his right flank (figure 1). the patient noticed the lesion approximately three months prior which then progressively grew. no palpable axillary or inguinal lymph nodes were noted. review of systems was abstract angiosarcoma is a rare malignant entity that typically presents as a rapidly progressing ecchymotic or cellulitis-like lesion with subsequent bleeding or ulceration. atypical presentations have been described, such as cases mimicking rosacea, making the diagnosis more challenging. due to the high rate of local recurrence, metastasis, and disease-specific mortality, early identification and treatment is critical. here we describe a 69-year-old man with a vascular targetoid lesion clinically consistent with a targetoid hemosiderotic hemangioma (thh); however, biopsy was consistent with an angiosarcoma. early diagnosis of this lesion resulted in prompt wide local excision and no detection of metastasis. this case report highlights the importance of thorough evaluation of new onset vascular lesions and the unique thh-like presentation of an angiosarcoma. introduction case report skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 423 figure 1. 2cm targetoid vascular lesion on right flank unremarkable. a 5mm punch biopsy of the lesion was performed. histopathologic evaluation revealed vascular proliferation within the superficial to mid dermis composed of enlarged and pleomorphic endothelial cells. many of the endothelial cells formed small irregular ectatic vascular units, with crack-like spaces. scattered mitotic figures along with single scattered enlarged endothelial cells with background hemorrhage were observed (figure 2). the endothelial cells were highlighted on cd31 immunostaining and negative with sox-10, melan-a, and hhv-8 immunostaining (figure 3). mib-1 immunostaining revealed an increased proliferation index. this was consistent with a diagnosis of an angiosarcoma. a full body pet scan demonstrated no areas of concern for metastasis. a wide local excision with 2.5cm margins followed by reconstruction with a posteriorly-based advancement flap was completed. the tumor was completely excised with negative margins. this case was discussed at a multidisciplinary tumor board where surgical treatment alone was determined to be sufficient for this localized, small lesion. monitoring will consist of pet scans every six months for two years cutaneous angiosarcoma is an aggressive malignant lesion frequently presenting as a raised purplish-red papule on the head and neck. early presentations can often be dangerously mistaken as a benign vascular lesion, leading to delayed diagnosis, delayed treatment, and worse prognosis6. histological examination of angiosarcoma include irregular vascular channels and atypical endothelial cells that may appear normal, pleomorphic, and hyperchromatic7. immunohistochemistry may be positive for cd34 and cd317.the local recurrence rates of cutaneous angiosarcoma after surgical excision have been reported to range from 35-86%8. a retrospective study conducted at the mayo clinic reported a 5-year-recurrence free survival of 16%, a 5-year local regional control of 18%, and a 5-year overall survival of 38% among patients treated for cutaneous angiosarcoma 9. another study conducted among patients diagnosed with angiosarcoma of the face and scalp reported an even higher recurrence rate of 93.8%8. imaging including mri, ct, and pet scan is crucial for staging and management of angiosarcoma. due to its rare incidence, the optimal treatment is not currently established9. wide local excision with negative margins is the gold standard; however, currently, there are no specific margins recommended by the nccn guidelines. the multifocal nature of the lesion and propensity for tissue infiltration often result in positive resection margins, recurrence, and metastasis of the tumor10 discussion skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 424 figure 2. 5mm bunch biopsy of right flank. h&e stain a) 4x showing an atypical vascular proliferation and background hemorrhage within the dermis b) 40x highlighting the atypical endothelial cells demonstrating mitotic figures, arranged singly and forming small irregular vessels figure 3. cd31 staining highlighting the atypical endothelial cells and vessels (10x) and an additional peripheral ecchymotic ring. thh lesions typically occur on the proximal extremities and trunk. several studies have reported a cyclical variation in palpability, in skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 425 in contrast, targetoid hemosiderotic hemangioma (thh), also known as hobnail hemangioma, is a benign vascular lesion that often presents as a solitary annular violaceous papule surrounded by a pale ring size, and color of the lesions, which contributes to the challenge in diagnosis11. histological findings of thh include noncircumscribed dermal vascular proliferations that are usually found within the superficial and mid dermal layers of the skin11. the vascular channels are lined by a single layer of “hobnail-like” endothelial cells. excision of a thh lesion is mostly curative, and malignant transformation, recurrence or systemic metastases have not been reported12. in this case we demonstrate a unique clinical presentation of angiosarcoma in which a targetoid vascular lesion was identified, a finding more commonly associated with thh. the wide variety of clinical presentations of thh and angiosarcoma can make initial diagnosis challenging; however, early clinical suspicion is critical due to their vastly different prognoses. conflict of interest disclosures: none funding: none corresponding author: alexandra flamm, md assistant professor of dermatology & pathology department of dermatology penn state hershey medical center 500 university drive hershey, pa 17033 phone: 717-531-8307 fax: 717-531-4702 email: aflamm@pennstatehealth.psu.edu references: 1.gaballah, a. h. et al. angiosarcoma: clinical and imaging features from head to toe. br. j. radiol. 90, 20170039 (2017). 2.mendenhall, w. m., mendenhall, c. m., werning, j. w., reith, j. d. & mendenhall, n. p. cutaneous angiosarcoma. am. j. clin. oncol. 29, 524–528 (2006). 3.holden, c. a., spittle, m. f. & jones, e. w. angiosarcoma of the face and scalp, prognosis and treatment. cancer 59, 1046– 1057 (1987). 4.vora, r., anjaneyan, g. & gupta, r. cutaneous angiosarcoma of head and neck. indian j. dermatol. 59, 632 (2014). 5.perez, m. c. et al. cutaneous angiosarcoma: a single-institution experience. ann. surg. oncol. 20, 3391– 3397 (2013). 6.dossett, l. a., harrington, m., cruse, c. w. & gonzalez, r. j. cutaneous angiosarcoma. curr. probl. cancer 39, 258–263 (2015). 7.selim, a., khachemoune, a. & lockshin, n. a. angiosarcoma: a case report and review of the literature. cutis-new york76, 313 (2005). 8.ogawa, k. et al. treatment and prognosis of angiosarcoma of the scalp and face: a retrospective analysis of 48 patients. br. j. radiol. 85, e1127–33 (2012). 9.patel, s. h. et al. angiosarcoma of the scalp and face: the mayo clinic experience. jama otolaryngol. head neck surg. 141, 335–340 (2015). 10.pawlik, t. m. et al. cutaneous angiosarcoma of the scalp: a multidisciplinary approach. cancer 98, 1716–1726 (2003). 11.bingham, l. g. & davis, d. m. clinicopathologic challenge. international journal of dermatology vol. 47 991–992 (2008). 12.kakizaki, p., valente, n. y. s., paiva, d. l. m., dantas, f. l. t. & gonçalves, s. v. c. b. targetoid hemosiderotic hemangioma case report. an. bras. dermatol. 89, 956–959 (2014). conclusion skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 639 original research disparities in access to teledermatology during the covid-19 pandemic in detroit, michigan angela j. jiang, md,1 reem kashlan, bs, mph,2 christine joseph, phd,3 amy tang, phd,3 henry w. lim, md1 1 henry ford health system, department of dermatology, detroit, mi 2 wayne state university, school of medicine, detroit, mi 3 henry ford health system, department of public health sciences, detroit mi teledermatology has evolved significantly since its advent in the early 1990s. while it was first used to improve access to dermatologic care in rural areas, teledermatology has also been implemented to aid primary care practices and emergency departments.1,2 in the era of covid and social distancing, teledermatology is playing a crucial role in caring for dermatology patients while also preserving the health of both patients and providers.3–5 while teledermatology may in theory improve access to dermatologic care, disparities in access to virtual care may in fact be present. for example, a recent henry ford health system (hfhs) study demonstrated patients who used patient portals were more likely to be white and more frequent users of healthcare.6 other studies corroborated the possibility that spanish-speaking patients, older patients, and lower socioeconomic groups may have decreased access to teledermatology.7,8 in contrast, teledermatology significantly increased access to dermatology care for patients with medicaid when the teledermatology consultation was initiated by their primary care physician rather than the patient themselves.9 additional literature regarding access to telehealth remains lacking. abstract background: teledermatology became a necessary modality for dermatologic patient care during the covid-19 pandemic. due to disparities in access to technology, “the digital divide” refers to worsening health care disparities despite telemedicine’s best efforts to improve access. methods: retrospective chart review was performed of all patients who were scheduled to be seen in dermatology during the first wave of pandemic (march 27, 2020 to april 27, 2020). demographic characteristics of patients who pursued virtual visits was compared with those who did not. results: compared to patients who canceled office visits, patients who completed virtual visit appointments were more likely to be younger (mean age 37.8 versus 45.5 years), female (68.7% versus 62.9%, p=0.01), unmarried (68.7% versus 61.0%, p<0.01). of the diagnoses rendered during virtual visits, 53.3% were associated with dermatoses. conclusions: patient populations above the age of 65 were less likely to complete a video visit, regardless of socioeconomic factors. future policies must take marginalized populations into account to improve ease of access to technological services. introduction skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 640 previous utilization of teledermatology was limited significantly due to lack of reimbursement. however, beginning on march 17, 2020, the centers for medicare and medicaid services (cms) and other major private payers have expanded telehealth coverage during the pandemic. the cms policy change eliminated many barriers to implementation of telemedicine including lack of reimbursement, licensing restrictions, and health insurance portability and accountability act (hipaa) compliance.10 accessibility to dermatologic care may be improved due to these policy changes for some patients; however, based on studies regarding patient portal usage, patients of lower socioeconomic status (ses) or older than 65 years of age may be marginalized.11 during the covid-19 pandemic, dermatology providers at hfhs contacted patients directly to offer virtual visits in lieu of office visits to mitigate covid-19 exposure risk. the aim of this study is to compare the demographics of patients who elected to pursue virtual visits with those who deferred a virtual visit and while in-person appointments were canceled. using billing data, a retrospective review was performed of all patients scheduled for an office visit between march 27, 2020 and april 27, 2020. we determined whether patients who were scheduled during this time period completed a virtual visit, including telephone, video, or store-andforward visit; or had a canceled in-person office visit. patient characteristics patient characteristics were obtained through chart review including age, gender, race, ethnicity, marital status, insurance type, and zip code. patient age was categorized into two groups: younger and older than 18 years. patients over the age of 65 were investigated separately as well. race was categorized as white, black, or other. a social deprivation index (sdi) was linked to patient zip code.12 sdi is used to quantify the socioeconomic variation in health outcomes, and is a function of demographic characteristics collected by the american community survey.12,13 insurance was categorized into four groups: commercial, medicaid, medicare, and unknown. statistical analyses differences in characteristics of patients who rescheduled to virtual visits and those who canceled office visits were compared by use of chi-square and t-tests. multivariate logistic regression was used to model these associations and generate odds ratios adjusted for the other variables included in the model. statistical significance was set at p<0.05. this project was reviewed by henry ford health system’s institutional review board, and informed consent was waived. 4015 patients were scheduled for in-person office visits during the study period (figure 1). of those, 14 patients kept in-person for office visits in lieu of virtual visits and were excluded from the analysis. of the remaining 4001 patients, 498 (12.4%) patients successfully completed a virtual visit appointment and 3503 (87.6%) had elected to cancel their appointments. five hundred methods results skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 641 figure 1. number of patients scheduled for office visits during the first wave of the covid-19 pandemic and sixteen virtual visits were completed by the 498 patients during this time period. compared to patients who canceled office visits, patients who completed virtual visit appointments were more likely to be younger patients (mean age 37.8 versus 45.5 years), female (68.7% versus 62.9%, p=0.01), unmarried (68.7% versus 61.0%, p<0.01), and had commercial insurance (56.4% versus 51.5%) or medicaid (23.3% versus 19.6%, p<0.01) (table 1). between groups, there was no difference based on race (p=0.51) or sdi score (0.74). on multivariate analysis, patients with virtual visits were more likely to be younger than 18 (aor 1.44, 95% ci 1.12-1.85, p<0.005), and female (aor 1.30, 95% ci 1.06-1.60, p=0.01). patients with medicare insurance were less likely to have completed a virtual visit (aor 0.73, 95% ci 0.57-0.95, p=0.017). diagnoses of the 498 virtual visits, 820 separate icd diagnostic codes were used (table 2). of the diagnoses rendered during virtual visits, 12.4% were related to neoplasms, 53.3% were associated with dermatoses, and 6.5% were related to medication monitoring. of the various dermatoses, 20.9% of virtual visits were related to acne or rosacea, 7.4% atopic dermatitis, and 5.1% psoriasis. age in the pediatric population, patients with medicaid insurance were less likely to schedule a virtual visit compared with patients with commercial insurance (53.1% versus 62.0%); however, this did not reach statistical significance (p=0.095) (table 3). compared to white patients, blacks were less likely to have a completed virtual visit appointment (41.0% versus 51.9%, p=0.068). moreover, pediatric patients with skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 642 table 1. characteristics of all patients associated with completed virtual visit during the covid-19 pandemic characteristic all virtual visits canceled visits p-value aor* (95% ci) p-value age <18 751 (18.8%) 129 (25.9%) 622 (17.8%) <0.001 1.44 (1.12 – 1.85) 0.004 ≥18 3250 (81.2%) 369 (74.1%) 2881 (82.2%) gender female 2547 (63.7%) 342 (68.7%) 2205 (62.9%) 0.01 1.30 (1.06 – 1.60) 0.011 male 1454 (36.3%) 156 (31.3%) 1298 (37.1%) race white 2086 (52.1%) 248 (49.8%) 1838 (52.5%) reference black 1204 (30.1%) 155 (31.1%) 1049 (29.9%) 0.51 0.99 (0.79 – 1.24) 0.947 other 711 (17.8%) 95 (19.1%) 616 (17.6%) 1.00 (0.76 – 1.30) 0.999 marital status not married 2480 (62.0%) 342 (68.7%) 2138 (61.0%) 0.001 married 1521 (38.0%) 156 (31.3%) 1365 (39.0%) 0.85 (0.68 – 1.07) 0.17 insurance commercial 2085 (52.1%) 281 (56.4%) 1804 (51.5%) <0.001 reference medicaid 804 (20.1%) 116 (23.3%) 688 (19.6%) 0.97 (0.76 – 1.23) 0.782 medicare 1006 (25.1%) 92 (18.5%) 914 (26.1%) 0.73 (0.57 – 0.95) 0.017 unknown 106 (2.6%) 9 (1.8%) 97 (2.8%) 0.57 (0.29 – 1.15) 0.118 sdi score (mean +/ sd) 49.1 ± 34.7 (n=3975) 49.6 ± 33.5 (n=495) 49.1 ± 34.9 (n=3480) 0.74 *adjusted odds ratio (aor) obtained from multivariate analysis table 2. frequency of diagnoses among patients with completed virtual visits diagnosis frequency neoplasms 102 (12.4%) acne/rosacea 171 (20.9%) atopic dermatitis 61 (7.4%) psoriasis 42 (5.1%) dermatitis, unspecified 163 (19.9%) medication monitoring 53 (6.5%) other 228 (27.8%) skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 643 table 3. characteristics among patients with completed virtual visits, stratified by age of patient characteristic all virtual visits canceled visits p-value aor (95% ci)* p-value pediatric patients gender female 420 (55.9%) 75 (58.1%) 345 (55.5%) 0.58 1.15 (0.78 – 1.70) 0.47 male 331 (44.1%) 54 (41.9%) 277 (44.5%) race white 322 (42.9%) 67 (51.9%) 255 (41.0%) reference black 204 (27.2%) 28 (21.7%) 176 (28.3%) 0.068 0.68 (0.39 – 1.19) 0.18 other 225 (30.0%) 34 (26.4%) 191 (30.7%) 0.73 (0.46 – 1.18) 0.20 insurance commercial 410 (54.6%) 80 (62.0%) 330 (53.1%) 0.095 reference medicaid 312 (41.5%) 47 (36.4%) 265 (42.6%) 0.87 (0.55 – 1.36) 0.53 unknown 29 (3.9%) 2 (1.6%) 27 (4.3%) 0.32 (0.07 – 1.39) 0.13 sdi score (mean ± sd) 49.4 ± 35.7 (n=750) 43.6 ± 33.3 (n=129) 50.6 ± 36.1 (n=621) 0.041 0.98 (0.91 – 1.05) 0.51 adult patients age (mean ± sd) 52.6 ± 18.8 (n=3250) 47.4 ± 19.1 (n=369) 53.3 ± 18.6 (n=2881) <0.0001 0.83 (0.76 – 0.89) <0.0001 gender female 2127 (65.4%) 267 (72.4%) 1860 (64.6%) 0.003 1.33 (1.04 – 1.70) 0.023 male 1123 (34.6%) 102 (27.6%) 1021 (35.4%) race white 1764 (54.3%) 181 (49.1%) 1583 (54.9%) reference black 1000 (30.8%) 127 (34.4%) 873 (30.3%) 0.10 1.080 (0.81 – 1.45) 0.61 other 486 (15.0%) 61 (16.5%) 425 (14.8%) 1.03 (0.74 – 1.43) 0.87 insurance commercial 1675 (51.5%) 201 (54.5%) 1474 (51.2%) 0.024 reference medicaid 492 (15.1%) 69 (18.7%) 423 (14.7%) 1.03 (0.75 – 1.41) 0.85 medicare 1006 (31.0%) 92 (24.9%) 914 (31.7%) 1.24 (0.89 – 1.74) 0.21 unknown 77 (2.4%) 7 (1.9%) 70 (2.4%) 0.72 (0.32 – 1.59) 0.21 sdi score (mean ± sd) 49.1 ± 34.5 (n=3225) 51.8 ± 33.5 (n=366) 48.7 ± 34.6 (n=2859) 0.11 1.00 (0.96 – 1.04) 1.00 *adjusted odds ratio (aor) obtained from multivariate analysis skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 644 lower sdi scores (i.e. less deprivation) were more likely to have a completed virtual visit appointment (score of 43.6 versus a score of 50.6 in patients with canceled appointments, p=0.041). statistical significance of lower sdi scores was not maintained on multivariate analysis, potentially due to interactions between sdi and race as well as a relatively low sample size of virtual visits (n-129). in adult patients, younger patients were more likely to complete a virtual visit with average age 47.4 ± 19.1 years versus 53.3 ± 18.6 years in patients who canceled (p<0.0001) (table 3). female patients (72.5% versus 64.6%, p=0.003) and commercial insurance (54.5% versus 51.2%, p=0.024) were significantly more likely to have a virtual visit. when adjusted for all variables, the associations between younger age, female gender and successful virtual visits remained statistically significant. interestingly, black patients (34.4% versus 30.3%, p=0.10) and higher sdi scores (51.8 ± 33.5 versus 48.7 ± 34.6, p=0.11) were associated with successful virtual visits, though these did not meet statistical significance. when patients >65 years of age were analyzed as a separate cohort, age, gender, race, and sdi were not shown to be significantly associated with virtual visit completion (table 4). with the burgeoning need for telemedicine and teledermatology, recent research has raised concerns for demographic differences in access to virtual visits in medicine, now called “the digital divide.”14–16 beginning in march 2020, many dermatology practices implemented teledermatology rapidly as a response to the spread of covid-19 and the necessity for social distancing. recent studies have shown that dermatology patients over the age of 65 and those with medicare insurance were less likely to pursue teledermatology visits.17,18 strikingly, patients with medicaid were more likely to pursue a televisit in lieu of an office visit in a similar study.19 studies in other specialties have found similar trends with fewer virtual visits completed by patients who are older, poorer, non-english-speaking, and female.20 some hypotheses propose that younger patients with medicaid insurance may prefer virtual visits due to lack of private transportation or access to childcare. women, however, may have a disproportionate distribution of childcare duties with children staying home, which may limit access to telehealth.21,22 most articles posit that older patients pursue fewer dermatology virtual visits due to lower technical literacy as well more common complaints related to keratinocyte carcinomas.18,19 in this study, the pediatric patient population who completed virtual visits appeared to mirror health disparities previously reported in pediatric dermatology patients, with improved access in patients with commercial insurance, lower sdi scores, and white race.23,24 in the adult patient population, younger, female patients with commercial insurance were more likely to complete virtual visits. this observation with younger and female patients remained statistically significant after adjustment for all other variables in the adult population. notably, black patients and patients with higher sdi scores were more likely to have virtual visits; however, this did not meet statistical significance. in this study, our data overall suggests that virtual visits were more accessible to patients who were younger with commercial insurance. discussion skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 645 our findings in older patients are similar to previously reported findings with patients over 65 less likely to pursue virtual visits. lower deprivation indices and race in table 4. characteristics among >65-year-old patients with completed virtual visits characteristic all virtual visits canceled visits p-value age (mean ± sd) 74.0 ± 7.4 (n=995) 74.1 ± 7.7 (n=82) 74.0 ± 7.3 (n=913) 0.96 gender female 559 (56.2%) 43 (52.4%) 516 (56.5%) 0.48 male 436 (43.8%) 39 (47.6%) 397 (43.5%) race white 712 (71.6%) 53 (64.6%) 659 (72.2%) 0.35 black 197 (19.8%) 20 (24.4%) 177 (19.4%) other 86 (8.6%) 9 (11.0%) 77 (8.4%) insurance commercial 132 (13.3%) 7 (8.5%) 125 (13.7%) 0.38 medicaid 7 (0.7%) 0 7 (0.8%) medicare 850 (85.4%) 75 (91.5%) 775 (84.9%) unknown 6 (0.6%) 0 6 (0.7%) sdi score (mean ± sd) 39.7 ± 32.3 (n=988) 43.4 ± 31.5 (n=81) 39.4 ± 32.3 (n=907) 0.28 elderly patients were not associated with increased likelihood of successful virtual visits. while socioeconomic factors appear to play a role in disparities in access to teledermatology for patients below the age of 65, it appears that age is the pivotal factor in determining access to teledermatology care during the covid-19 pandemic. one confounding issue, however, is that most older patients are often seen in dermatology for full skin examinations which may have been deferred during the pandemic due to overall lack of urgency. while skin examinations were deferred during the covid pandemic, early studies posit that skin cancer diagnoses may have been delayed during the pandemic.25 as previous studies have reported, older patients may defer virtual visits due to the desire for inperson evaluations of possible skin neoplasms.18 moreover, elderly patients have low self-perceived ability to perform many functions on a patient portal that would allow them to access a physician, even with additional aid.26 41% of medicare beneficiaries lack access to either a computer with high-speed internet connection at home or smartphone with a wireless data plan, with 26% lacking access to both.27 future technology employed in patient care should consider ease of use for the elderly as well as optimization of evaluation of neoplasms to help improve access for the elderly patient population. government legislation should also consider the digital inequities that exist throughout the nation as well.16 with regards to the utility of teledermatology, virtual visits appear to be most often utilized for dermatoses, which made up 53.3% of icd codes used. another potential use for telehealth is for patients who were scheduled to follow up for medication monitoring purposes, such as for isotretinoin. as previously mentioned, the evaluation of neoplasms remains limited in telemedicine. as our experience with telemedicine continues to grow, it is possible that teledermatology may be optimized to allow for patients with known common dermatoses and medication monitoring to be skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 646 seen via virtual visits and allow for easier inperson access for patients with neoplasms and unknown dermatoses. limitations of this study include a single institution experience with overall low adoption of virtual visits amongst canceled appointments. though virtual visits were offered to all patients by physicians, interprovider variability in offering virtual visits may be present. moreover, patients who did not have an office visit scheduled prior to the covid-19 pandemic but scheduled a subsequent virtual visit were not included. in this study, initial chief complaints were unable to be recorded. there was a lower sample size for adults over the age of 65, with only 82 patients completing a virtual visit. lastly, our study had few non-englishspeaking patients, who have been shown to be disadvantaged in access to telemedicine during the covid-19 pandemic.19,28 however, this study demonstrates preliminary evidence of the persistence of disparities in teledermatology during the covid-19 pandemic. additional investigation into factors affecting patients’ decision to pursue virtual visits as well as further demographic information of patients completing virtual visits with the increasing implementation of teledermatology should be considered. during the covid-19 pandemic, telemedicine has become essential. health care providers must remain mindful of patients who may not have easy access to technology, who may not have the technological literacy to pursue virtual visits, or even may not have complaints easily evaluated by teledermatology. though federal policy has improved reimbursement to allow for remote delivery of care,29 additional policies are needed to improve ease of access to phone and internet services and technological advances.27 electronic medical records should be modified to improve ease of access for all patients. though limitations in teledermatology are present, teledermatology will remain a presence in caring for our patients, and providers and emrs must continue to collaborate to optimize use for both providers and patients. limitations conclusion skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 647 conflict of interest disclosures: none funding: none corresponding author: angela jiang, md 3031 w grand blvd, ste 800 detroit, mi 48202 phone: 937-515-1561 email: angelajiangmd@gmail.com references: 1. coates sj, kvedar j, granstein rd. teledermatology: from historical perspective to emerging techniques of the modern era: part i: history, rationale, and current practice. j am acad dermatol. 2015;72(4):563-574; quiz 575576. doi:10.1016/j.jaad.2014.07.061 2. duong ta, cordoliani f, julliard c, et al. emergency department diagnosis and management of skin diseases with real-time teledermatologic expertise. jama dermatol. 2014;150(7):743-747. doi:10.1001/jamadermatol.2013.7792 3. chen y, pradhan s, xue s. what are we doing in the dermatology outpatient department amidst the raging of the 2019 novel coronavirus? j am acad dermatol. 2020;82(4):1034. doi:10.1016/j.jaad.2020.02.030 4. perkins s, cohen jm, nelson ca, bunick cg. teledermatology in the era of covid-19: experience of an academic department of dermatology. j am acad dermatol. published online april 16, 2020. doi:10.1016/j.jaad.2020.04.048 5. price kn, thiede r, shi vy, curiellewandrowski c. strategic dermatology clinical operations during covid-19 pandemic. j am acad dermatol. published online april 8, 2020. doi:10.1016/j.jaad.2020.03.089 6. peltz-rauchman cd, divine g, mclaren d, et al. response to survey directed to patient portal members differs by age, race, and healthcare utilization. jamia open. 2019;2(4):429-433. doi:10.1093/jamiaopen/ooz061 7. bush ra, richardson ac, cardona-grau d, din h, kuelbs cl, chiang gj. patient portal usage in pediatric urology: is it meaningful use for everyone? urol pr. 2018;5(4):279-285. doi:10.1016/j.urpr.2017.05.002 8. mcgrail km, ahuja ma, leaver ca. virtual visits and patient-centered care: results of a patient survey and observational study. j med internet res. 2017;19(5):e177. doi:10.2196/jmir.7374 9. uscher-pines l, malsberger r, burgette l, mulcahy a, mehrotra a. effect of teledermatology on access to dermatology care among medicaid enrollees. jama dermatol. 2016;152(8):905-912. doi:10.1001/jamadermatol.2016.0938 10. lee i, kovarik c, tejasvi t, pizarro m, lipoff jb. telehealth: helping your patients and practice survive and thrive during the covid-19 crisis with rapid quality implementation. j am acad dermatol. 2020;82(5):1213-1214. doi:10.1016/j.jaad.2020.03.052 11. mcgee js, reynolds rv, olbricht sm. fighting covid-19: early teledermatology lessons learned. j am acad dermatol. 2020;83(4):12241225. doi:10.1016/j.jaad.2020.06.027 12. social deprivation index (sdi). accessed january 30, 2021. https://www.grahamcenter.org/rgc/maps-data-tools/sdi/socialdeprivation-index.html 13. bureau uc. american community survey (acs). the united states census bureau. accessed january 30, 2021. https://www.census.gov/programs-surveys/acs 14. watts g. covid-19 and the digital divide in the uk. lancet digit health. 2020;2(8):e395-e396. doi:10.1016/s2589-7500(20)30169-2 15. ramsetty a, adams c. impact of the digital divide in the age of covid-19. j am med inform assoc jamia. 2020;27(7):1147-1148. doi:10.1093/jamia/ocaa078 16. bakhtiar m, elbuluk n, lipoff jb. the digital divide: how covid-19’s telemedicine expansion could exacerbate disparities. j am acad dermatol. 2020;83(5):e345-e346. doi:10.1016/j.jaad.2020.07.043 17. su my, smith gp, das s. trends in teledermatology utilization during clinic reopening following covid-19 closures. j am acad dermatol jaad. published online december 1, 2020. doi:10.1016/j.jaad.2020.12.019 18. miller rc, stewart cr, lipner sr. retrospective study of trends in dermatology telemedicine and in-person visits at an academic center during covid-19. j am acad dermatol. published online november 19, 2020. doi:10.1016/j.jaad.2020.11.015 19. franciosi eb, tan aj, kassamali b, o’connor dm, rashighi m, lachance ah. understanding the impact of teledermatology on no-show rates and health care accessibility: a retrospective chart review. j am acad dermatol. published skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 648 online september 11, 2020. doi:10.1016/j.jaad.2020.09.019 20. eberly lauren a., khatana sameed ahmed m., nathan ashwin s., et al. telemedicine outpatient cardiovascular care during the covid-19 pandemic. circulation. 2020;142(5):510-512. doi:10.1161/circulationaha.120.048185 21. alon t, doepke m, olmstead-rumsey j, tertilt m. the impact of covid-19 on gender equality. national bureau of economic research; 2020. doi:10.3386/w26947 22. syed st, gerber bs, sharp lk. traveling towards disease: transportation barriers to health care access. j community health. 2013;38(5):976-993. doi:10.1007/s10900-0139681-1 23. lie e, psoter kj, püttgen kb. lower socioeconomic status is associated with delayed access to care for infantile hemangioma, a cohort study. j am acad dermatol. published online october 1, 2018. doi:10.1016/j.jaad.2018.09.041 24. chaudhry sb, armbrecht es, shin y, et al. pediatric access to dermatologists: medicaid versus private insurance. j am acad dermatol. 2013;68(5):738-748. doi:10.1016/j.jaad.2012.10.034 25. asai y, nguyen p, hanna tp. impact of the covid-19 pandemic on skin cancer diagnosis: a population-based study. plos one. 2021;16(3):e0248492. doi:10.1371/journal.pone.0248492 26. gordon np, hornbrook mc. differences in access to and preferences for using patient portals and other ehealth technologies based on race, ethnicity, and age: a database and survey study of seniors in a large health plan. j med internet res. 2016;18(3):e50. doi:10.2196/jmir.5105 27. roberts et, mehrotra a. assessment of disparities in digital access among medicare beneficiaries and implications for telemedicine. jama intern med. 2020;180(10):1386. doi:10.1001/jamainternmed.2020.2666 28. blundell ar, kroshinsky d, hawryluk eb, das s. disparities in telemedicine access for spanishspeaking patients during the covid-19 crisis. pediatr dermatol. published online december 27, 2020. doi:10.1111/pde.14489 29. medicare telemedicine health care provider fact sheet | cms. accessed february 1, 2021. https://www.cms.gov/newsroom/factsheets/medicare-telemedicine-health-careprovider-fact-sheet skin november 2017 volume 1 issue 3 copyright 2017 the national society for cutaneous medicine 128 original research ingenol mebutate 0.06% gel for field treatment of actinic keratosis on 250 cm 2 of skin on trunk and extremities: a randomized dose-finding trial daniel m. siegel md a , emil tanghetti md b , neil brody md phd c , michael freeman facd d , torsten skov phd e , astrid h. petersen phd e , fabrice clonier msc e , lynda spelman facd f a long island skin cancer and dermatologic surgery, new york, ny, usa b center for dermatology and laser surgery, sacramento, ca, usa c brody dermatology, new york, ny, usa d the skin centre, gold coast, australia e leo pharma, ballerup, denmark f veracity clinical research, brisbane, australia abstract background: field treatment of actinic keratosis (ak) can eradicate clinical and sub-clinical lesions; treatments for extended skin areas are required. methods: this randomized, double-blind, vehicle-controlled trial (nct01998984) evaluated ingenol mebutate (ingmeb) 0.06% gel for ak treatment over extended areas. adults with 5–20 ak lesions within a 250 cm 2 area of skin on the trunk (except chest) or extremities were randomized to: 2 days vehicle, 2 days ingmeb (2d, n=55); 1 day vehicle, 3 days ingmeb (3d, n=59); 4 days ingmeb (4d, n=49); or 4 days vehicle (n=61). week 8 primary endpoint was complete clearance of ak lesions; secondary endpoints included reduction in ak count and partial clearance. adverse events (aes) were recorded and local skin responses (lsrs) assessed. a hierarchical testing scheme, starting with 3d versus vehicle, was used. results: in total, 224 patients were randomized. at week 8, for 2d, 3d, 4d, and vehicle groups, complete clearance rates were 12.7%, 5.1%, 26.8%, and 0.0% (3d vs. vehicle, p=0.18); reductions in ak count were 63.0%, 66.8%, 73.6%, and 11.9%, respectively. lsr scores peaked at day 5 (3d and 4d), and days 5 and 10 (2d). application-site pain and pruritus were common aes. of 15 neoplasm aes, 14 were designated keratoacanthomas and one squamous cell carcinoma by central pathological review. the 4d group was closed based on pre-defined criteria. conclusions: all three regimens were effective at reducing ak count on trunk/extremities. the 4d treatment was not well tolerated. complete clearance was not significantly different to vehicle. skin november 2017 volume 1 issue 3 copyright 2017 the national society for cutaneous medicine 129 actinic keratosis (ak) results from cumulative ultraviolet (uv) light exposure. 1 ak lesions present as hyperkeratotic papules and plaques often on an erythematous background; 2 they may progress to squamous cell carcinoma (scc) if left untreated, and have a higher risk of progression the longer they are present. 3,4 management of ak is typically achieved through lesion-directed or field-directed topical therapy. 3,5,6 advanced imaging techniques show that areas of sun-exposed skin may contain both sub-clinical and clinically visible lesions, as well as areas of dysplastic cells in fields of cancerization. 6–8 treating the entire field of sun-damaged skin, rather than only the clinically apparent lesions, is therefore ideal. ingenol mebutate (ingmeb) (picato ® leo pharma a/s ballerup, denmark) is indicated for the topical treatment of ak in areas of skin up to 25 cm 2 . a short course of ingmeb gel (two or three consecutive days) was associated with a marked improvement in the clearance of ak on the face/scalp (ingmeb 0.015% gel) and trunk/extremities (ingmeb 0.05% gel) versus placebo. 9 the treatment effect was maintained long term. 10 some patients, however, may require treatment over areas larger than 25 cm 2 . a new-formulation gel containing a higher concentration of ingmeb, is being investigated for use over larger treatment areas. previous investigations identified 0.06% as the maximum tolerated concentration for a 2-day (d) regimen applied to the full face, full balding scalp or approximately 250 cm 2 on the chest. 11 as a more aggressive regimen may be required for the treatment of the trunk and extremities, the current trial was designed to investigate the efficacy of extending the duration of ingmeb 0.06% gel treatment (2-, 3or 4d regimens), compared with vehicle, over 250 cm 2 of skin. study design this was a phase ii, randomized, multicenter (14 in the usa; 13 in australia), double-blind, vehicle-controlled trial (nct01998984). the protocol was approved by relevant review boards at each center. informed written consent was obtained from all patients and the trial conducted according to the principles of the declaration of helsinki. patients (≥ 18 years) with 5–20 clinically typical, visible, discrete ak lesions within a contiguous area of approximately 250 cm 2 of skin on the trunk (except chest) or extremities were eligible for enrollment (supplementary materials provide exclusion criteria). ingmeb 0.06% gel or vehicle gel was applied topically to a contiguous area of approximately 250 cm 2 on the trunk (except chest) or extremities, daily for four days. patients were randomized 1:1:1:1 (stratified per trial site) to one of four treatment groups (supplementary figure 1): 2 days vehicle, 2 days ingmeb (2d); 1 day vehicle, 3 days ingmeb (3d); 4 days ingmeb (4d); 4 days vehicle (vehicle group). treatment assignment was pre-planned and generated through an interactive web response system. outcomes the primary endpoint was complete clearance of ak lesions (akclear 100) at week 8. secondary endpoints at week 8 were reduction in ak count from baseline and partial clearance of ak lesions methods skin november 2017 volume 1 issue 3 copyright 2017 the national society for cutaneous medicine 130 (akclear 75), defined as ≥ 75% reduction from baseline in the number of clinically visible ak lesions. dermatologic assessment of the treatment area was performed by a board-certified dermatologist or equivalent at baseline, and at weeks 4 and 8. where possible, the same dermatologist performed all examinations on an individual patient. treatment areas were documented on a study transparency, using a 3-point landmark technique to locate and assess ak lesions during treatment. photodamage outcome assessments, comprising a visual and tactile evaluation by investigators of the change from baseline in the photo-damage of the patient’s skin, were performed at week 8. safety endpoints included the incidence and severity of local skin responses (lsrs) and adverse events (aes), recorded at days 1, 5, 10, 17, 31 and 56. lsrs were assessed quantitatively as described previously. 12 patients completed a burning-sensation diary on all treatment days, recording onset, duration and feeling of burning (rated on a 5-point descriptive scale: no burning to unbearable burning). at week 8, they completed a treatment satisfaction questionnaire for medication (tsqm) v1.4 13 . cosmetic outcome was self-assessed using two questionnaires evaluating changes in overall appearance and feel of skin (rated on a 4-point scale: worsened, no change, somewhat improved, much improved). statistical analysis sample size was determined based on the number of patients required to obtain 80% power when detecting a difference in akclear 100 rates between ingmeb and vehicle treatment groups, assuming a true estimate of 28% in the ingmeb groups and 7% in the vehicle group (significance level 0.05). efficacy analyses were performed on the full analysis set, defined as all randomized patients. a closed testing procedure was used to account for multiplicity. the 4d ingmeb treatment group was closed early on the recommendation of a data-monitoring committee (dmc) (see below) and patients were excluded from the final statistical model. thereafter, the 3d ingmeb treatment group was to be tested first and, provided a significant result was observed, the 2d ingmeb arm was to be tested, thereby ensuring that the overall significance level did not exceed 5%. the safety analysis set included all patients who received at least one application of trial medication and had safety information available post-treatment. safety results were summarized using descriptive statistics. two interim safety analyses (based on number of dose-limiting events) were conducted by a dmc when 12 and 23 patients, respectively, were randomized to each group and followed for 17 days. primary and secondary endpoints were analyzed by a cochran-mantel-haenszel test, adjusting for analysis site. reduction in ak count from baseline to week 8 was analyzed using a negative binomial regression (supplementary materials). stata ® version 13.2 was used for imputation of missing ak count. statistical analyses were undertaken using sas software, version 9.3 (sas institute inc., cary, nc, usa) and the medical dictionary for regulatory activities version 15.1 used for coding of aes and medical history. skin november 2017 volume 1 issue 3 copyright 2017 the national society for cutaneous medicine 131 patients in total, 266 patients enrolled in the study (03 february–22 august 2014) (figure 1); 224 were randomized to treatment (42 screening failures), forming the full analysis and safety sets. although the 4d group was closed early, data are presented here because of the high number of patients completing treatment. regarding baseline demographics/disease characteristics, the median duration of ak in patients from australia was more than twice that of patients from the usa (table 1). over 90% of patients had received previous treatment for ak. treatment adherence was high; all four doses were received by 92.9% of patients. 2d, 2-day group; 3d, 3-day group; 4d, 4-day group; ae, adverse event; ingmeb, ingenol mebutate. figure 1. subject flow through the trial results skin november 2017 volume 1 issue 3 copyright 2017 the national society for cutaneous medicine 132 efficacy at week 8, akclear 100 was 12.7%, 5.1%, 26.8%, and 0.0% for 2d, 3d, 4d, and vehicle groups, respectively (table 2). there was no difference in akclear 100 between the 3d and vehicle groups (p=0.18). the hierarchical analysis of the primary and secondary endpoints, and the absence of a statistically significant difference in the primary comparison (3d ingmeb vs. vehicle) meant statistical significance could not be claimed for the 2d versus vehicle comparison, or any secondary efficacy endpoints. however, values are included for information. observed cases of akclear 100 varied by country and by baseline ak count. akclear 100 was higher in the usa than australia and for patients with baseline ak counts of 5–9 lesions versus those with 10–20 lesions (table 2). table 1. baseline demographics and disease characteristics full analysis set (n=224) usa (n=92) australia (n=132) sex, n (%) male 144 (64.3) 62 (67.4) 82 (62.1) female 80 (35.7) 30 (32.6) 50 (37.9) age, years mean (sd) 68.3 (10.5) 66.3 (10.4) 69.7 (10.3) race, n (%) white 224 (100.0) 92 (100.0) 132 (100.0) fitzpatrick skin type, n (%) i – burns easily, never tans 77 (34.4) 12 (13.0) 65 (49.2) ii – burns easily, tans minimally 122 (54.5) 64 (69.6) 58 (43.9) iii – burns moderately, tans gradually (light brown) 22 (9.8) 13 (14.1) 9 (6.8) iv – burns minimally, always tans well (moderate brown) 3 (1.3) 3 (3.3) 0 (0.0) duration of ak, years median (range) 12.0 (0–44) 8.0 (0–44) 17.0 (0–44) baseline ak count median (range) 12 (5–20) 10 (5–20) 13 (6–20) ak, actinic keratosis; sd, standard deviation. n, number of patients. skin november 2017 volume 1 issue 3 copyright 2017 the national society for cutaneous medicine 133 table 2. akclear 100 and reduction in ak count at week 8 akclear 100, n (%) reduction in ak count from baseline, % (sd) ingmeb 0.06% gel vehicle (n=61) ingmeb 0.06% gel vehicle (n=61) 2d (n=55) 3d (n=59) 4d (n=49) 2d (n=55) 3d (n=59) 4d (n=49) overall a,b, 7.0 (12.7) c 3.0 (5.1) c 13.1 (26.8) c 0.0 (0) c 64.5 d,e 68.3 d,e n/a 11.9 d,e vehicle p-value vs. p=0.051 f,g p=0.18 f,g n/a n/a p<0.001 d p<0.001 d n/a by baseline ak count h 5–9 5/21 (23.8) 2/21 (9.5) 5/15 (33.3) 0/16 (0.0) n/a n/a n/a n/a 10–20 2/34 (5.9) 1/37 (2.7) 8/33 (24.2) 0/42 (0.0) n/a n/a n/a n/a by country h usa 7/24 (29.2) 2/26 (7.7) 6/16 (37.5) 0/24 (0.0) 78.7 (26.4) 73.6 (23.5) 73.4 (32.6) 10.0 (20.5) australia 0/31 (0.0) 1/32 (3.1) 7/32 (21.9) 0/34 (0.0) 50.9 (33.3) 61.2 (32.1) 73.7 (24.4) 12.7 (27.2) ak, actinic keratosis; cmh, cochran–mantel–haenszel; ingmeb, ingenol mebutate; n/a, not available; sd, standard deviation. n, number of patients. akclear 100, complete clearance of ak lesions from baseline; a multiple imputation. b based on 1000 imputations of ak count at week 8 using a negative binomial regression model with factors treatment and analysis site and with log of baseline ak count as offset. c n/1000 from 1000 imputations of ak count at week 8 using a negative binomial regression model with factors treatment and analysis site and with log baseline ak count as offset. d from negative binomial regression model with factors treatment and analysis site and with log of baseline ak count as offset. e ratio of adjusted means (95% ci), p value: 2d vs. vehicle: 0.40 (0.32–0.51), p<0.001; 3d vs. vehicle: 0.36 (0.29–0.45), p<0.001; 3d vs. 2d: 0.89 (0.70–1.14), p=0.36. f adjusted for analysis site. g cmh logit estimators were used for comparisons with vehicle due to absence of cleared patient in the vehicle group. h observed cases. skin november 2017 volume 1 issue 3 copyright 2017 the national society for cutaneous medicine 134 treatment differences should be considered with caution due to the hierarchical procedure defined in the protocol. however, in the primary analysis using the multiple imputation method (supplementary materials), and excluding the 4d group, the adjusted percentage reduction in ak count from baseline was significantly greater than vehicle (11.9%) for ingmeb 2d (64.5%, p<0.001) and 3d (68.3%, p<0.001) groups (table 2). for observed cases, the mean percentage reduction was numerically higher for the usa than australia in the 2d (78.7% versus 50.9%, respectively) and 3d (73.6% versus 61.2%, respectively) groups, but similar within the vehicle (10.0% versus 12.7%) groups. similarly, in the primary analysis, using the multiple imputation method and excluding the 4d group, akclear 75 was significantly greater than vehicle (2.0%) for ingmeb 2d (47.3%, p=0.002) and 3d (56.2%, p≤0.001) groups. safety at baseline, the mean (standard deviation) composite lsr scores were 1.5 (1.1), 1.7 (1.2), 1.7 (1.2) and 1.7 (1.3) for the 2d, 3d, 4d and vehicle groups, respectively. maximum mean composite lsr scores peaked at day 5 in the 3d and 4d groups and at days 5 and 10 in the 2d group. lsr scores in all ingmeb groups declined rapidly and were minimal four weeks after treatment (figure 2). the 4d group had the highest composite lsr score at day 5 (11.8), followed by the 3d (8.8) and 2d (7.3) groups. the vehicle group had similar scores at all visits, corresponding to baseline scores for the ingmeb groups. the majority of patients in the ingmeb groups experienced aes of mild or moderate intensity. there were 12 aes leading to treatment discontinuation in eight patients, including seven aes of application site pain. aes were considered to be treatment-related in most patients receiving ingmeb. the most common treatment-related aes in the ingmeb groups were application-site pain (including burning sensation reported in the burningsensation diary) (2d, 81.8%; 3d, 84.7%; 4d, 87.8%) and application-site pruritus (2d, 34.5%; 3d, 45.8%; 4d, 28.6%). maximum burning sensation scores were reported at days 1 and 2 in the 4d group and at days 3 and 4 in both the 2d and 3d groups. most patients in the vehicle group reported no burning sensation. sixteen aes (most reported as saes) of ‘neoplasms benign, malignant, and unspecified (including cysts and polyps)’ were reported inside the treatment area in 12 patients (australia, n=11; usa, n=1), distributed evenly across all ingmeb groups. ten patients had a history of skin cancer. fifteen aes were reviewed by a central pathologist (consent to follow up was not obtained for one patient with one event of intraepidermal carcinoma) and 14 were diagnosed as keratoacanthoma (ka), all in patients from australia. one was diagnosed as scc (supplementary table 1). no other treatment-related saes were reported. other observations patient tsqm-derived scores for satisfaction and effectiveness were significantly greater in the 2d and 3d ingmeb groups than vehicle skin november 2017 volume 1 issue 3 copyright 2017 the national society for cutaneous medicine 135 (p<0.001; supplementary table 2). the majority (80–98%) of patients in the ingmeb groups were assessed by investigators as having improvements (minor, moderate or marked) in their global photo-damage from baseline to week 8; 86% of patients in the vehicle group had no change (figure 3a). there was a trend towards higher outcome scores with the 2d and 3d groups in the usa versus australia; similar scores were observed in the 4d group (data not shown). across the ingmeb groups, improved changes in the overall appearance of the treatment area were reported by ≥ 80% of patients; improved changes in the overall feel of the treatment areas were reported by ≥ 70% of patients. little difference in patient-reported cosmetic outcome between ingmeb groups was observed (figure 3b). around 10% of patients reported overall cosmetic improvements with vehicle. 2d, 2-day group; 3d, 3-day group; 4d, 4-day group; ingmeb, ingenol mebutate; lsr, local skin responses. mean composite of lsr scores. a composite score was obtained by summing the 6 individual local skin responses (erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration) scores at each visit. figure 2. composite local skin responses over time skin november 2017 volume 1 issue 3 copyright 2017 the national society for cutaneous medicine 136 2d, 2-day group; 3d, 3-day group; 4d, 4-day group; ingmeb, ingenol mebutate. a) investigators’ global photo-damage outcome at week 8. the visual and tactile assessment of photodamage change from baseline in the treatment area included an integrated assessment of fine wrinkling, coarse wrinkling, mottled pigmentation, roughness, sallowness, skin laxity and telangiectasia. the scoring was on a 7-point symmetric scale: marked improvement, moderate improvement, minor improvement, no change, minor worsening, moderate worsening and marked worsening. b) patients’ cosmetic outcome assessment at end of treatment. figure 3. investigator and patient-reported cosmetic outcomes at week 8 in this trial, a 3d application of ingmeb 0.06% gel to a treatment area of approximately 250 cm 2 on the trunk or extremities reduced ak count. however, a statistically significant difference in the primary endpoint of complete clearance (akclear 100) at week 8 compared with vehicle was not observed (p=0.18). discussion skin november 2017 volume 1 issue 3 copyright 2017 the national society for cutaneous medicine 137 complete clearance rates observed in this trial were low overall, showed high variation, and a dependency on country and baseline ak count. when compared with ingmeb treatment of ak over a 25 cm 2 area, 9 lower complete clearance is to be expected because of the larger area and higher number of baseline lesions being treated. of note, complete clearance in the 3d arm (5.1%) was low versus other treatment groups; however, a high number (48.3%) of patients in this group had one or two ak lesions remaining (supplementary figure 2). complete clearance appeared to be higher for patients from the usa who generally had a shorter duration of ak and for those with fewer baseline ak lesions, suggesting that efficacy may be influenced by the extent of disease. one trial limitation was that no statistical claims can be made for the secondary endpoints, because of the pre-defined order of testing and lack of statistical significance for the primary endpoint. numerical and clinically relevant effects were observed with 2d, 3d and 4d regimens versus vehicle for secondary endpoints (partial clearance: 47.3%, 56.2%, 60.4%, vs. 2.0%, respectively; mean reduction in ak count: 64.5%, 68.3%, 73.6%, vs. 11.9%, respectively). similar partial clearance results have been observed in trials evaluating ingmeb on a treatment area of 25 cm 2 : lebwohl et al. reported partial clearance of 63.9% on the face/scalp and 49.1% on the trunk/extremities. they also reported a median percent reduction in lesion count of 83% and 75%, respectively, which was greater than vehicle (p<0.001). 9 in this study, the 2d and 3d treatments were well tolerated; the 4d treatment was not. based on the outcome of dmc interim safety analyses and pre-defined protocol criteria, the 4d treatment regimen was stopped prior to completing enrollment. consistent with previous findings, 9 application-site aes, including pain and pruritus, were the most frequent treatment-related events. the use of non-standardized reporting of endpoints hinders cross-trial comparison with other currently available fielddirected therapies, including 5fluorouracil, imiquimod, diclofenac and photodynamic therapy. 5 studies have generally focused on the face and scalp 14–17 rather than the extremities, where ak lesions are more difficult to treat and have shorter remission times. 10 partial, but not complete, clearance results from the current trial, investigating treatment in the trunk and extremities, compare well with two previous studies with imiquimod 2.5% and 3.75% that investigated a scalp/facial treatment area > 25 cm 2 . 18,19 in those studies, complete clearance rates were 30.6% and 35.6% for 2-week 18 and 25.0% and 34.0% for 3-week on/off/on treatment regimens. 19 partial clearance rates were 48.1% and 59.4% 18 and 42.7% and 53.7%, 19 respectively. compliance is an issue with patientadministered treatment 5,9 and may explain why efficacy reported in clinical trials is not always reflected in the realworld. in a recent study, 88% of patients treated in a clinical setting were nonadherent with topical treatment; adherence fell, in line with increasing duration of treatment. 20 shorter, simpler treatment regimens should improve adherence and outcomes. 21 in this trial, adherence with ingmeb was high, with 92.9% of patients receiving all four applications of treatment, confirming findings from previous ingmeb studies. 9 skin november 2017 volume 1 issue 3 copyright 2017 the national society for cutaneous medicine 138 another advantage of short-course treatment is the predictable timing and relatively short duration of lsrs, which should improve patient satisfaction. 21 in the current study, lsr scores peaked at day 5 in the 3d and 4d groups and at days 5 and 10 in the 2d group; responses were minimal four weeks after treatment. these findings are similar to those reported over a 25 cm 2 treatment area – lsr score peaked at day 4 for the face/scalp and at days 3, 8 and 15 for the trunk/extremities. 9 in this study, 14 of 15 neoplasms ‘benign, malignant and unspecified’ were designated ka by central pathology review, all in fair-skinned (type i) australian patients. although uv light is a major risk factor for development, kas have been observed following a number of different skin therapies including imiquimod, chemical peel, and cryosurgery. 22–24 this treatmentassociated development of ka may be due to inflammation-mediated mitogenactivated protein (map) kinase stimulation in the presence of uvinduced activating ras mutations in keratinocytes in sun-damaged skin. 25 as the frequency of ka increases with increased sun exposure, 6,25 this may partially explain why kas were observed exclusively in australian patients. another contributing factor to the formation of kas may be activation of nuclear factor kappa b (nf-κb), which is activated in both acute and chronic inflammation. 26 nf-κb is activated after imiquimod treatment 27 and treatment with ingmeb gel (leo pharma, unpublished data). nf-κb is a promoter of solid organ tumors, 28 and hyperactivation of nf-κb in skin may lead to ka formation. 29 this may also explain why primarily kas, but not sccs, are seen after ingmeb treatment, as there is accumulating evidence from mouse studies that nf-κb inhibition, rather than activation, induces epidermal hyperplasia and promotes development of cutaneous scc. 30–33 the impact of ak on an individual’s physical and emotional well-being should be considered in clinical management. ak may be associated with pain, sensitivity to touch, bleeding, concern about appearance (e.g. embarrassment about scarring), and can negatively impact health-related quality of life. 34–37 in this study, ≥ 70% of patients reported improved cosmetic outcomes with ingmeb, with improved appearance and feel of the treated area. the reduction in ak count from baseline and the partial clearance results, along with the predictable lsr profile, support the efficacy of ingmeb 0.06% gel optimized for larger treatment areas of approximately 250 cm 2 on the trunk and extremities, when applied for 2 or 3 consecutive days. conflict of interest disclosures: dr siegel reports personal fees from leo pharma, outside the submitted work. dr tanghetti, dr brody, and dr freeman report no conflicts of interest. dr skov is an employee of leo pharma. dr petersen and mr clonier were employees of leo pharma at the time of preparation of the manuscript. dr petersen is now an employee of sanofi genzyme and mr clonier is now an employee of ppd. dr spelman reports fees as principal investigator in the trial and for consultancy for leo pharma outside the submitted work; honorarium from galderma, outside the submitted work. conclusions skin november 2017 volume 1 issue 3 copyright 2017 the national society for cutaneous medicine 139 acknowledgements: the authors would like to acknowledge patrick griffin, msc, of imed comms, an ashfield company for medical writing support that was funded by leo pharma, in accordance with good publication practice (gpp3) guidelines. the authors thank the investigators who participated in this study. funding: this study was funded by leo pharma. corresponding author: daniel m. siegel, md long island skin cancer and dermatologic surgery 994 jericho turnpike, suite 103 new york, ny, usa (631) 864-6647 cyberderm@dermsurg.org references: 1. berman b, cockerell cj. pathobiology of actinic keratosis: ultraviolet-dependent keratinocyte proliferation. j am acad dermatol 2013;68(suppl 1):s10–s19. 2. einspahr jg, stratton sp, bowden gt, et al. chemoprevention of human skin cancer. crit rev oncol hematol 2002;41:269–85. 3. werner rn, sammain a, erdmann r, hartmann v, stockfleth e, nast a. the natural history of actinic keratosis: a systematic review. br j dermatol 2013;169(3):502–18. 4. criscione vd, weinstock ma, naylor mf, et al. actinic keratoses: natural history and risk of malignant transformation in the veterans affairs topical tretinoin chemoprevention trial. cancer 2009;115:2523–30. 5. uhlenhake ee. optimal treatment of actinic keratoses. clin interv aging 2013;8:29–35. 6. dodds a, chia a, shumack s. actinic keratosis: rationale and management. dermatol ther (heidelb) 2014;4:11–31. 7. slaughter dp, southwick hw, smejkal w. field cancerization in oral stratified squamous epithelium; clinical implications of multicentric origin. cancer 1953;6:963–8. 8. malvehy j. a new vision of actinic keratosis beyond visible clinical lesions. j eur acad dermatol venereol 2015;29(suppl 1):3–8. 9. lebwohl m, swanson n, anderson ll, et al. ingenol mebutate gel for actinic keratosis. n engl j med 2012; 366:1010–9. 10. lebwohl m, shumack s, gold ls, et al. longterm follow-up study of ingenol mebutate gel for the treatment of actinic keratosis. jama dermatol 2013;149:666–70. 11. hanke cw, berman b, swanson n, et al. dosefinding clinical study with ingenol mebutate for field treatment of actinic keratosis up to 250 cm2 on full face, scalp, or chest (pa15), seminars in cutaneous medicine and surgery 2015;(34) (supplement 6):s107–108. 12. rosen r, marmur e, anderson l, et al. a new, objective, quantitative scale for measuring local skin responses following topical actinic keratosis therapy with ingenol mebutate. dermatol ther (heidelb) 2014;4(2):207–219. 13. atkinson mj, sinha a, hass sl, et al. validation of a general measure of treatment satisfaction, the treatment satisfaction questionnaire for medication (tsqm), using a national panel trial of chronic disease. health and quality of life outcomes 2004;2(1):12. 14. tanghetti e1, werschler p. comparison of 5% 5-fluorouracil cream and 5% imiquimod cream in the management of actinic keratoses on the face and scalp. j drugs dermatol 2007;6:144–7. 15. ostertag ju, quaedvlieg pjf, van der geer s, et al. a clinical comparison and long-term followup of topical 5-fluorouracil versus laser resurfacing in the treatment of widespread actinic keratosis. lasers surg med 2006;38:731–9. 16. smith sr, morhenn vb, piacquadio dj. bilateral comparison of the efficacy and tolerability of 3% diclofenac sodium gel and 5% 5fluorouracil cream in the treatment of actinic keratoses of the face and scalp. j drugs dermatol 2006;5:156–9. 17. berman b, nestor ms, newburger j, et al. treatment of facial actinic keratoses with aminolevulinic acid photodynamic therapy skin november 2017 volume 1 issue 3 copyright 2017 the national society for cutaneous medicine 140 (alapdt) or ingenol mebutate 0.015% gel with and without prior treatment with alapdt. j drugs dermatol 2014;13:1353–6. 18. swanson n, smith cc, kaur m, et al. imiquimod 2.5% and 3.75% for the treatment of actinic keratoses: two phase 3, multicenter, randomized, double-blind, placebo-controlled studies. j drugs dermatol 2014;13:166–9. 19. hanke cw, beer kr, stockfleth e, et al. imiquimod 2.5% and 3.75% for the treatment of actinic keratoses: results of two placebocontrolled studies of daily application to the face and balding scalp for two 3-week cycles. j am acad dermatol 2010;62:573–81. 20. shergill b, zokaie s, carr aj. non-adherence to topical treatments for actinic keratosis. patient prefer adherence 2013;8:35–41. 21. stockfleth e, peris k, guillen c, et al. a consensus approach to improving patient adherence and persistence with topical treatment for actinic keratosis. int j dermatol 2015;54:509–15. 22. campalani e, holden ca. keratoacanthoma associated with the use of topical imiquimod. clin exp dermatol 2013;38(5):555–6. 23. cox s. rapid development of keratoacanthomas after a body peel. dermatol surg 2003;29(2):201–3. 24. kaptanoglu af, kutluay l. keratoacanthoma developing in previous cryotherapy site for solar keratosis. j eur dermatol venereol 2006;20(2):197–8. 25. selmer j, skov t, spelman l, weedon, d. squamous cell carcinoma and keratoacanthomas are biologically distinct and can be diagnosed by light microscopy: a review. histopathology 2016;69(4):535–1. 26. zhang q, lenardo mj, baltimore d. 30 years of nf-kb: a blossoming of relevance to human pathobiology. cell 2017;168:37–57. 27. li zj, sohn kc, choi dk, et al. roles of tlr7 in activation of nf-κb signaling of keratinocytes by imiquimod. plos one 2013;8(10):e77159. 28. basseres ds, baldwin as. nuclear factor-κb and inhibitor of κb kinase pathways in oncogenic initiation and progression. oncogene 2006;25(51):6817–0. 29. poligone b, hayden ms, chen l, pentland ap, jimi e, ghosh s. a role for nf-κb activity in skin hyperplasia and the development of keratoacanthomata in mice. plos one 2013;8(8):e71887. 30. costanzo m, baryshnikova a, bellay j, et al. the genetic landscape of a cell. science 2010;327(5964):425–31. 31. dajee m, lazarov m, zhang jy, et al. nf-κb blockade and oncogenic ras trigger invasive human epidermal neoplasia. nature. 2003;421(6923):639–3. 32. seitz cs, lin q, deng h, khavari pa. alterations in nf-κb function in transgenic epithelial tissue demonstrate a growth inhibitory role for nf-κb. proceedings of the national academy of sciences 1998;95(5):2307–12. 33. van hogerlinden m, rozell bl, ährlund-richter l, toftgård r. squamous cell carcinomas and increased apoptosis in skin with inhibited rel/nuclear factor-κb signaling. cancer res 1999;59(14):3299–03. 34. holmes c, foley p, freeman m, chong ah. solar keratosis: epidemiology, pathogenesis, presentation, and treatment. australas j dermatol 2007;48(2):67–6. 35. alam m. actinic keratoses: prevalence, pathogenesis, presentation, and prevention. adv stud med 2006;6(8a):s785–0. 36. esmann s, jemec gb. management of actinic keratosis patients: a qualitative study. j dermatolog treat 2007;18(1):53–8. 37. tennvall gr, norlin jm, malmberg i, et al. health related quality of life in patients with actinic keratosis--an observational study of patients treated in dermatology specialist care in denmark. health qual life outcomes 2015;13:111. skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 56 brief article the importance of clinicopathological correlation: a case of xanthoma disseminatum shreya patel, md1, tania j. phillips, md1 1department of dermatology, boston university school of medicine, boston, ma, usa xanthoma disseminatum (xd) is a very rare, non-familial non-langerhans cell histiocytosis.1-2 classically, xd presents as yellow-brown or red-brown papules on the face, trunk, and flexural areas.1-5 mucous membrane involvement may also occur in 40% -60% of cases.1-5 this disease is more common in men (2.4:1 ratio) and younger patients, and laboratory findings usually show normolipidemic or slightly hyperlipidemic blood levels.1-4 the diagnosis of xd is based on clinical suspicion, in combination with laboratory and pathology results. here we describe a misdiagnosed case of xd, as an example to highlight the importance of clinicopathological correlation with xanthomatous eruptions. a 70-year-old male presented with a fourmonth history of firm red pruritic papules on the face, neck, trunk, bilateral axillae, and bilateral thighs (figures 1a, 1b, 1c and 1d). the patient reported no oral or genital lesions and took no chronic medications. the patient was otherwise healthy and asymptomatic. previously, the patient was seen at an outside clinic where the diagnosis of eruptive xanthomas was made based on a right thigh biopsy consistent with xanthomas. the clinical findings did not show typical eruptive xanthomas or extensor involvement. laboratory testing showed mildly elevated cholesterol 291 (normal: <200) and low-density lipoprotein 223 (normal: <100); beta-2 microglobulin, protein electrophoresis, complete blood count, hba1c, and comprehensive metabolic panel were normal. abstract xanthoma disseminatum (xd) is a rare disease that presents with pruritic papules, classically involving the extensor surfaces and mucosal areas. we present a case of xd that was misdiagnosed as eruptive xanthomas and eventually self-resolved. self-resolving xd may be within a spectrum of adult-onset juvenile xanthogranuloma. however, as there may be systemic consequences of xd, it is critical to ensure these patients obtain a complete evaluation and close follow-up. introduction case report skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 57 figure 1 xanthomas on the a. left axilla and b. right thigh at the time of presentation. xanthomas on the c. left axilla and d. right thigh five weeks later at a follow-up visit the biopsy specimen was re-evaluated at our pathology laboratory (figure 2) and showed a nodular, superficial dermal collection of cd68-positive foamy histiocytes with occasional touton giant cells and intermixed lymphocytic infiltrate with few eosinophils and neutrophils. these findings were consistent with xanthoma disseminatum. a computed tomography scan of the brain was normal. the patient was counseled that surgical removal and carbon dioxide laser were options for cosmetic treatment, but the patient declined any intervention. after one month, the patient reported a spontaneous resolution of 80% of his lesions, except for a few lesions on his axillae and groin (figures 1c and 1d). xd is a rare non-langerhans cell histiocytosis that distinctively involves the flexural areas and mucous membranes.1-2, 5 the pathogenesis is understood to be a reactive proliferative histiocytosis with secondary lipid deposition.5-6 xd is associated with upper airway lesions, cns involvement of hypothalamus and pituitary causing mild diabetes insipidus, and rarely with plasma cell dyscrasias and monoclonal gammopathy.1-2,5 xd has a variable prognosis, with three subtypes: a) selfresolving, as in our patient, b) persistent disease, and c) rare systemic progression with organ dysfunction and cns involvement.4,6 there is no consensus on xd treatment; options include surgical removal, carbon dioxide laser treatment, cryotherapy, intralesional steroids, 2chlorodeoxyadenosine, and electrocoagulation.1,3,5 surgical removal and carbon dioxide laser have shown the best cosmetic outcomes, though 2chlorodeoxyadenosine has recently demonstrated efficacy.1,5 radiation therapy is effective for airway obstruction, while cyclophosphamide is used for mucosal lesions.1,5 our patient had no evidence of mucosal lesions or airway obstruction and declined any intervention. the differential diagnosis of xd includes adult-onset juvenile xanthogranuloma, eruptive xanthomas, as well as other xanthomatous diseases. the prognosis of each disease varies and, thus, can impact the management of these patients. histologically, xd resembles juvenile xanthogranuloma, which has a benign discussion skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 58 prognosis.1 however, the disease typically affects children under the age of 2 and self figure 2 histopathology of a right thigh biopsy, which showed a superficial dermal nodule of cd68-positive foamy histiocytes, as well as a few touton giant cells seen in the enlarged image resolves; adult-onset juvenile xanthogranuloma is rare.1 our patient was initially misdiagnosed with eruptive xanthomas, which, unlike xd, are associated with hypertriglyceridemia and commonly involve the extensor surfaces.3 overall, xd is a rare disease that can be difficult to distinguish from adult-onset juvenile xanthogranuloma; the latter may be within a spectrum of self-resolving xd. however, the consequences of xd can be systemic, and in a minority of cases, lifethreatening. therefore, it is critical to ensure these patients obtain a complete laboratory and imaging evaluation to rule out systemic involvement and close follow-up. conflict of interest disclosures: none funding: none acknowledgements: the case was presented at a meeting of the new england dermatological society at boston university on december 5th, 2020, which concurred with our diagnosis of xd corresponding author: shreya patel, md department of dermatology boston university school of medicine 609 albany street boston, ma, 02118 phone: 973-922-0433 fax: 219-912-3782 email: dermshreya@gmail.com references: 1. goodman wt, barrett tl. chapter 91: histiocytoses. in: dermatology (bolognia jl, conclusion skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 59 schaffer jv, cerroni l, eds.). 4th edn. elsevier, 2018:1614-33. 2. pinto m, escalaya g, escalaya m, et al. xanthoma disseminatum: case report and literature review. endocrine practice. 2010; 16(6): 1003-1006. 3. kashif m, kumar h, khaja m. an unusual presentation of eruptive xanthoma: a case report and literature review. medicine. 2016; 95(37) 4. park m, boone b, devos s. xanthoma disseminatum: case report and mini-review of the literature. acta dermatovenerologica croatica. 2014; 22(2): 150-150. 5. briones nf, hogikyan nd, fullen dr, et al. cutaneous and laryngopharyngeal papules of xanthoma disseminatum successfully treated with 2-chlorodeoxyadenosine. jaad case reports. 2018; 4(10): 990. 6. gong hz, zheng hy, li j. xanthoma disseminatum. the lancet. 2018; 391(10117): 251. introduction • papulopustular rosacea is a phenotype of rosacea characterized by papules and pustules located centrally on the face1 • oral antibiotics such as tetracyclines are first-line treatments for patients whose disease does not respond to topical therapies or for patients with multiple papules and pustules2 • sarecycline is a narrow-spectrum antibiotic approved by the us food and drug administration in 2018 for treatment of moderate to severe acne vulgaris3 • because of the well-established role for oral tetracyclines in rosacea and to limit emergence of antibiotic-resistant bacteria, a pilot study was conducted to assess oral sarecycline in adults with papulopustular rosacea (clinicaltrials.gov identifier: nct04555525) methods • this was a prospective, parallel-group, 12-week, randomized, investigator-blinded, pilot study of oral sarecycline treatment for adults with moderate to severe papulopustular rosacea (figure 1) • eligible participants were adults (aged ≥18 years) with moderate or severe rosacea based on investigator global assessment (iga) rating with ≥15 and ≤50 facial papules/ pustules and ≤2 facial nodules • statistical analyses were conducted on an intention-totreat basis; all tests were 2-sided and interpreted at a 5% significance level figure 1. study design ae, adverse event; iga, investigator global assessment; qd, once daily; r, randomization; sga, subject global assessment. results disposition and baseline characteristics • 102 adults with moderate-to-severe papulopustular rosacea were enrolled; 97 completed the study (sarecycline [n=72]; multivitamin [n=25]) • most participants were female (n=80 [82%]) and white (n=95 [98%]), with mean (standard deviation) age of 52.4 (14.5) years efficacy • sarecycline was associated with significantly greater percentage of participants achieving iga endpoint at week 12 vs multivitamin (coprimary endpoint; p<0.0001; figure 2) – significant differences in iga score in favor of sarecycline vs multivitamin were observed as early as week 4 (21% vs 8%; p<0.0001) figure 2. participants achieving iga scores of clear/almost clear at week 12 (coprimary endpoint) iga, investigator global assessment. • sarecycline treatment was associated with statistically significantly greater reduction in inflammatory lesion count at week 12 vs multivitamin (coprimary endpoint; p<0.0001; figure 3) – rapid reduction in inflammatory lesion count was observed with sarecycline vs multivitamin as early as week 4 (figure 3) figure 3. percent change from baseline in inflammatory lesion counts grey shading indicates coprimary endpoint at week 12. secondary endpoints and skin symptoms • at week 12, absent or trace ratings were significantly better in the sarecycline vs multivitamin group for facial symptoms of burning (p=0.038), erythema (p<0.0001), and pruritus (p=0.023; figure 4); significant differences were also observed for absent or trace dryness (p=0.02) and oiliness (p=0.039) figure 4. participants with absent/trace in facial symptoms at week 12 safety • 26 adverse events (aes) occurred in 16 participants in the sarecycline group – 7 rated as mild, 17 as moderate, 2 as severe – no serious aes reported • sarecycline was discontinued in 3 participants, with 2 aes (headache and gastroenteritis) considered probably related to sarecycline • aes of interest with a tetracycline derivative that occurred in the sarecycline group were nausea (n=2), headache (n=2), and facial sunburn (n=2) oral sarecycline for treatment of papulopustular rosacea: results of a pilot study evaluating efficacy and safety james q. del rosso, do,1 leon h. kircik, md,2-6 cheryl effron, md,7 zoe d. draelos, md8 1jdr dermatology research and thomas dermatology, las vegas, nv; 2icahn school of medicine at mount sinai, new york, ny; 3indiana university medical center, indianapolis, in; 4physicians skin care, pllc, louisville, ky; 5dermresearch, pllc, louisville, ky; 6skin sciences, pllc, louisville, ky; 7cosmetic dermatology of orange county, huntington beach, ca; 8dermatology consulting services, pllc, high point, nc acknowledgments: this study was supported by almirall, llc. medical writing, editorial assistance, and graphical support were provided under the direction of the authors by medthink scicom. references: 1. dahl. rosacea: pathogenesis, clinical features, and diagnosis. in: post tw, ed. uptodate. waltham, ma: wolters kluwer; 2020. 2. maier. management of rosacea. in: post tw, ed. uptodate. waltham, ma: wolters kluwer; 2020. 3. sarecycline [package insert]. exton, pa: almirall; 2020. conclusions • in this pilot study, oral sarecycline demonstrated effectiveness for treatment of papulopustular rosacea in adults as early as 4 weeks based on iga scores and reductions in inflammatory lesion counts • sarecycline improved facial symptoms, including burning, erythema, and pruritis • sarecycline was associated with a favorable safety and tolerability profile, with aes consistent with prior studies • additional studies are warranted to further evaluate oral sarecycline as treatment for papulopustular rosacea 1 enrolled participants (n=102) participants completing study (n=97) oral sarecycline, weight-based dose, qd (n=72) oral multivitamin, 1 tablet, qd (n=25) r 3:1 baseline week 12week 8week 4 coprimary outcome measures at week 12 • percentage of participants with iga score of clear or almost clear • percent reduction of inflammatory lesions secondary endpoints and safety and tolerability assessments assessments: • participants with iga score of clear/almost clear at 4 and 8 wk • reduction of inflammatory lesions at weeks 4 and week 8 • sga (rated at each study visit) • aes • local signs and symptoms (facial skin) figure 1 2 75 16 0 20 40 60 80 100 clear/almost clear p ar tic ip an ts , % sarecycline (n=72) multivitamin (n=25) p<0.0001 figure 2 3 -56 -71 -80 -31 -44 -60 -100 -80 -60 -40 -20 0 0 4 8 12 sarecycline (n=72) multivitamin (n=25) p<0.0001 p=0.0002 p<0.0001 figure 3 time, wk r ed uc tio n fr om b as el in e, % 4 96 63 94 76 12 76 0 20 40 60 80 100 burning erythema pruritis p ar tic ip an ts , % sarecycline (n=72) multivitamin (n=25) p=0.023p=0.038 p<0.0001 skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 240 in-depth review nutrition education toolbox for hidradenitis suppurativa jennifer m. fernandez md, rd1, joi lenczowski md2, jennifer l. hsiao md3, vivian y. shi md4 1university of arizona, college of medicine; tucson, az, usa 2virginia commonwealth university, department of dermatology, richmond, va, usa 3university of california los angeles, department of medicine, division of dermatology, los angeles, ca, usa 4university of arkansas for medical sciences, department of dermatology; little rock, ar, usa background emerging evidence suggests that diet influences hidradenitis suppurativa (hs) symptoms.1–4 recent survey studies indicate that up to 90% of hs patients have attempted to manage hs through dietary changes, with up to 65% of patients reporting that dietary changes were beneficial.1,5 price et al. identified dietary modification to be the most commonly self-employed complementary alternative medicine (cam) intervention implemented by hs patients.5 though current evidence supporting dietary recommendations in hs is low to moderate in quality,6 patients still frequently express interest in discussing dietary changes with their healthcare providers. however, providing nutrition education during clinic visits can be time consuming, and physicians may not feel equipped to do this. referring patients to a registered dietitian (rd) for hs is often not feasible due to limited insurance coverage for nutrition visits. though dietary changes are commonly implemented by hs patients, there is currently no comprehensive hs nutritional guide. our goal is to provide practical, cost-conscious nutrition recommendations as an adjunct to conventional medical treatments for hs. herein, we provide information in a handout that was developed with input from hs specialists, a registered dietitian, and a culinary specialist. impact of diet the proposed mechanism of dietary involvement in hs is largely extrapolated from the literature on acne given the similar pathogenesis.7,8 refined carbohydrates abstract diet has been shown to influence disease activity in hidradenitis suppurativa (hs). modification of dietary intake is the most commonly used lifestyle intervention in hs, and patients frequently report hs improvement after implementing dietary changes. providing nutrition education may be perceived as not feasible within the time constraints of an outpatient office visit, and many physicians may also not feel equipped to do this. in addition, most insurances have limited coverage for nutrition visits. however, dietary changes may be employed as a low-cost adjunctive treatment option that can be combined with conventional medical treatment to mitigate hs symptoms. though dietary modification has been increasingly recognized as a commonly used and influential factor in hs management, there is no comprehensive hs nutritional guide. herein, we provide tools for both physicians and patients to facilitate evidence-based nutrition education in hs through collaboration with dermatologists specializing in hs, a registered dietitian, and a culinary specialist. introduction skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 241 increase insulin levels, and dairy increases insulin and insulin-like growth factor-1 (igf1).9,10 subsequent hyperinsulinemia causes a nuclear androgen repressor, forkhead box protein o1 (foxo1), to enter the cytoplasm, activating mtorc1 (the kinase mammalian target of rapamycin complex 1) signaling, leading to increased sebaceous lipogenesis and contributing to follicular occlusion.9,10 increased androgenic signaling due to exogenous hormones in dairy products and lack of nuclear androgen suppression with foxo1 may increase the production of keratinocytes and induce subsequent follicular blockage in acne and hs.9 as such, it may be beneficial for patients to avoid dairy and refined carbohydrates. additionally, hyperglycemia due to excessive carbohydrate consumption can increase circulating inflammatory cytokines.11–13 an imbalance of omega-6 to omega-3 fatty acids can lead to production of prostaglandins, thromboxanes, and leukotrienes through the arachidonic acid pathway, and excessive saturated fat intake can have inflammatory effects by disrupting normal immune cell function.12,14,15 high salt intake can also alter immune activity and inhibit growth of beneficial bacteria that are part of a healthy gut microbiome.16,17 dietary intake is immediately modifiable with minimal side effects, making diet an important target for disease management. physicians should counsel patients that improvement in hs symptoms after dietary changes may take time and may require long-term dietary adjustments. given this, dietary interventions may be more suitable for a more motivated subset of patients. impact of weight, diabetes, and metabolic syndrome obesity is associated with insulin resistance and chronic low-grade inflammation due to circulating cytokines such as tumor necrosis factor (tnf) and interleukin (il)-6.18 the excessive adipocytes present with obesity can perpetuate production of inflammatory cytokines such as tnf that are also implicated in hs pathogenesis.19 obesity correlates with increased hs disease severity and is commonly observed in hs patients.20 more than half of hs patients are either overweight (27%) or obese (36%).20 obesity likely contributes to increased hs severity through inducing inflammation and excessive friction.21 weight loss of more than 15% is associated with a clinically significant decrease in hs severity.22 diabetes and metabolic syndrome can also accompany hs. rates of diabetes mellitus in hs patients range from 5% to 20%,23 and approximately 40% of hs patients have metabolic syndrome.24 obesity and diabetes can both cause hyperinsulinemia, promoting excessive lipogenesis and contributing to follicular occlusion in hs.7 factors affecting food choices many factors may contribute to food selection in hs patients, such as limited mobility which may affect the ability to go food shopping, low socioeconomic status (ses), unemployment, financial hardship, poor mental health, and cultural preferences. hs is associated with low ses and with high levels of anxiety, depression, and loneliness and low selfesteem.25 characteristic symptoms of hs including pain, malodorous discharge, and itch are major contributors to physical disability.26 research shows that several of the diets studied in hs may attenuate disease severity including the mediterranean diet, a brewer’s yeast-free diet, and a dairy-free diet.7,27,28 sample nutrition handouts for hs patients incorporating recommendations based on nutrition recommendations skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 242 these studies are provided in figures 1, 2, 3, and 4.7,9,10,27–30 while daytime fasting over a prolonged period of time has been shown to decrease the number of abscesses and draining fistulas,3 persistent fasting is likely impractical for most patients. thus, a wellbalanced diet with an appropriate caloric intake may serve as a better approach for hs patients. foods to avoid yeast diets restricting the intake of yeast have shown positive results in hs, including brewer’s yeast that leads to fermentation in alcohol and baker’s yeast that causes baked products to rise; these yeasts are each comprised of a different strain of saccharomyces cerevisiae, a single-celled fungal organism.4,28 in an initial study with a small cohort, twelve hs patients followed a wheat and brewer’s yeast-free diet for 12 months after surgical excision of hs lesions and were instructed to avoid baked goods (such as pizza, cake, bread, etc.), vinegar, black tea, soy sauces, beer, wine, fermented cheese, and mushrooms.28 all 12 patients experienced regression of hs lesions, with immediate reappearance of lesions upon reintroduction of brewer’s yeast, beer, or wheat and subsequent disappearance of lesions after those agents were removed from the diet again.28 a larger follow up study evaluated 37 hs patients who followed a yeast-free diet for six years after excision of hs lesions, with 70% reporting improvement in hs symptoms without other accompanying treatment, and 87% reporting recurrence of hs symptoms within a few days after consuming a restricted food.4 though the sample sizes in these studies are small and patients were also treated with surgery, the results after implementation of a yeast-free diet are promising. carbohydrates refined carbohydrates refined carbohydrates can lead to hyperinsulinemia which may exacerbate follicular occlusion.9,10,31 refined carbohydrates come from sweets, sugarcontaining beverages, many snack foods, and refined grains such as white rice, white bread, and pasta. grains at least half of all grains consumed should be whole grains such as 100% whole wheat bread, whole-grain pasta, and brown rice.32 added sugars dietary guidelines for americans 2015-2020 recommended that less than 10% of daily calories come from added sugars, a major dietary source of refined carbohydrates.32 nearly 80% of added sugars are from beverages, snacks, and sweets,32 so replacing these items with healthier options may significantly decrease intake of added sugars. sugar-sweetened beverages like soda, juice, and sports drinks contain calories but have minimal nutritional value. fruit drinks are often thought of as a healthy option, but they frequently contain added sugar. if fruit juice is consumed, it should be “100% fruit juice”, and it should be consumed in limited quantities (4-6 oz/day).32 lowcalorie beverages without added sugars should be encouraged. seltzer water, with a splash of 100% juice, or club soda with wedges of lemons, limes, or oranges can be a refreshing alternative to traditional juices and sodas. adding fresh fruit such as raspberries or vegetables such a sliced cucumber to water can also add a hint of flavor. unsweetened tea is a healthier alternative for sweetened tea. skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 243 figure 1. nutrition handout with recommendations for anti-inflammatory foods, dairy intake, and healthy snack options. figure 2. nutrition handout with recommendations for carbohydrate intake. skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 244 finding healthy and affordable snack options can be challenging, especially when. processed snacks, such as chips and cookies, are cheap and readily available eating fruits or vegetables as a snack can help patients reach the recommended daily intake of these food groups. while nuts are high in calories, they provide a source of healthy, anti-inflammatory fats, and unsalted nuts in ¼ cup portions make travel-friendly and convenient snacks. air-popped popcorn or whole grain crackers with almond butter are also healthy snack options. cravings for sweet treats can be satisfied with healthier alternatives such as baked apple wedges, sautéed banana slices, pear slices sprinkled with crushed walnuts, fruit salads, or frozen fruit puree popsicles. dairy dairy is defined as products made from the fluid form of milk such as cheese, yogurt, and cottage cheese. dairy products contribute many essential nutrients including calcium, vitamin d, and vitamin b12, among others.32 in a cohort of 43 hs patients who followed a dairy-free diet, 83% improved.7 hs patients who eliminate dairy may consume inadequate amounts of calcium and may require supplementation. other sources of dietary calcium include sardines and salmon, green leafy vegetables, soy products, beans, and nuts.29 soy products such as soy cheese and soymilk, almond milk, and rice milk can serve as dairy alternatives. foods to consume anti-inflammatory foods and the mediterranean-style diet the mediterranean diet and increased intake of omega-3 fatty acids are associated with lower hs severity scores.27 currently, there is no clear definition of an anti-inflammatory diet. however, the mediterranean diet is regarded as an anti-inflammatory diet and has been shown to decrease risk of cancer, cardiovascular disease, and diabetes, among other conditions.33 a mediterranean-style diet is a plant-based diet high in fiber and omega3 fatty acids which have anti-inflammatory effects. it is characterized by an abundance of fruits and vegetables that contain polyphenols that counteract inflammation. vegetables and fruits have a low caloric density and are high in fiber, both of which are important for weight control. unfortunately, only about 20% of americans consume the recommended amount of fruits and vegetables.32 major protein sources in the mediterranean diet include fish, nuts, and beans while animal proteins such as red meat and dairy are consumed in limited quantities. olive oil is the principal source of fat; saturated fat is limited. in addition, whole grains are emphasized over refined carbohydrates. fatty fish such as salmon, trout, or tuna are high in omega-3 fatty acids and should be consumed two times per week. other considerations portion sizes excessive portion sizes can contribute to overconsumption of calories, leading to obesity. serving sizes vary based on whether a food is cooked (takes up less space) or raw. serving sizes also vary for different food groups.32 for vegetables, one serving is typically ½ cup of cooked vegetables or 1 cup raw. a serving of fruit is ½ cup chopped fruit, one small fist-sized piece of fruit, or ¼ cup dried fruit. a serving of meat is typically 3-4 oz. a portion of dairy is 1 cup of milk or yogurt or 1.5 oz of cheese. while measuring cups and scales may be the most accurate way to measure foods, patients may find it more skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 245 figure 3. nutrition handout with general tips for healthful eating and portion sizes. figure 4. nutrition handout with tips for eating out. skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 246 practical to use parts of the hand (such as fingertip, palm, and clenched fist) to estimate portion sizes (figure 3). recommendations for eating out while eating out can be a fun social experience, portions can be excessive, and food is often high in fat and sodium. to limit excess calories, fat, and sodium, encourage patients to order from the lunch menu as portions tend to be smaller and cheaper than the dinner menu. ask for sauce on the side or no sauce as sauce can often be high in saturated fats. to avoid eating extremely large portions, patients may consider splitting an entrée. alternatively, requesting a to-go container when the order is placed and putting half of the food in the container before eating can help limit excessive consumption. avoid buffets as portion control is extremely challenging in this setting. choose water rather than juice, soda, or alcohol to curb cost and calories. food assistance options supplemental nutrition assistance program (snap), formerly called the food stamp program, is a government assistance program that distributes benefits monthly onto an electronic benefit transfer (ebt) card which can be used like a debit card.34 it can be used at various grocery stores, dollar stores, pharmacies, convenience stores, and big-box stores (such as walmart and target), among others.34 ebt cards allow purchase of fruits, vegetables, meat, poultry, fish, dairy, breads, and cereals, and other items.34 they cannot be used for alcohol or prepared or hot foods. food pantries and food banks are also sources of food distribution, and information about location of food pantries can be found at https://www.foodpantries.org/. as some patients may not have access to the internet, physicians may consider providing paper handouts. using coupons can also help save money. community supported agriculture (csa) programs are subscription-based programs that local farmers participate in, where consumers who purchase a subscription receive a box of produce and other farm goods such as eggs or meat several times per month. insurance coverage approximately a third (31.5%) of hs patients are insured by either medicare or medicaid, which is a significantly higher proportion than age-matched controls.35 for those with diabetes or kidney disease, medicare part b covers up to three visits per year with a registered dietitian,36 and this can be considered for motivated patients who meet criteria. medicaid nutrition benefits vary by state, and states are not required by the federal government to provide medical nutrition therapy (mnt) benefits, although about half of states offer some nutrition services benefits.37 coverage for nutrition visits with private insurances can vary greatly, so patients should be encouraged to contact their insurance provider to inquire about coverage. once insurance coverage for mnt is established, the website hosted by the academy of nutrition and dietetics can assist physicians and patients with finding a registered dietitian in their area (https://www.eatright.org/find-an-expert). more research is needed regarding the mechanism of diet in hs, but these studies are difficult to conduct given the unique dietary needs, preferences, and culinary and cultural practices of each individual. these studies may also require participation for an extended duration to adequately evaluate the impact of dietary modifications, which is further complicated by a high risk of poor dietary adherence. the benefit of restricting total caloric intake versus restricting specific conclusion https://www.foodpantries.org/ https://www.eatright.org/find-an-expert skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 247 food groups or ingredients in hs is largely unknown, and specific dietary guidelines for hs are lacking. nutrigenetics and nutrigenomics are at the forefront of applied nutrition research and can be incorporated into future diet-related investigations for hs patients. clinic visits between patients and dermatologists can often be limited by time constraints, and nutrition counseling from an rd is often not covered by insurance, so providing nutrition education to patients can be challenging. however, efforts should be made by hs physicians to address diet as part of their treatment plan. a healthy and well-balanced diet should be the foundation of dietary counseling. recommendations should be tailored to patients of varying ses with consideration of cultural preferences, food costs, access, and preparation time. in addition, being mindful of eating behaviors and recognizing the tendency to eat when under stress, or as a response to other emotions, can help prevent unnecessary calorie consumption. these strategies can be incorporated into comprehensive treatment plans to both help manage hs symptoms and to promote overall health. conflict of interest disclosures: vys is on the board of directors for the hidradenitis suppurativa foundation, is a stock shareholder of learn health and has served as an advisory board member, investigator, and/or received research funding from sanofi genzyme, regeneron, abbvie, eli lilly, novartis, sun pharma, leo pharma, pfizer, menlo therapeutics, burt’s bees, galderma, altus lab, gpskin and skin actives scientific. jlh has served as an advisor for novartis. there were no incentives or transactions, financial or otherwise, relevant to this manuscript. jennifer m. fernandez and joi lenczowski have no conflicts of interest. funding: none corresponding author: vivian y. shi, md associate professor, department of dermatology university of arkansas for medical sciences 4301 west markham, slot 576 little rock, arkansas 72205 phone: 501-686-5110 email: vivian.shi.publications@gmail.com references: 1. dempsey a, butt m, kirby js. prevalence and impact of dietary avoidance among individuals with hidradenitis suppurativa. dermatology. published online november 1, 2019:1-7. doi:10.1159/000503063 2. fernandez jm, marr kd, hendricks aj, et al. alleviating and exacerbating foods in hidradenitis suppurativa. dermatologic therapy. published online september 11, 2020. doi:10.1111/dth.14246 3. damiani, mahroum, pigatto, et al. the safety and impact of a model of intermittent, time-restricted circadian fasting (“ramadan fasting”) on hidradenitis 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fall in cellular inhibitor κb, and an increase in tumor necrosis factor α messenger rna by mononuclear cells in healthy human subjects. metabolism. 2006;55(9):11771185. doi:10.1016/j.metabol.2006.04.016 14. simopoulos ap. omega-6/omega-3 essential fatty acid ratio and chronic diseases. food reviews international. 2004;20(1):77-90. doi:10.1081/fri-120028831 15. enos rt, davis jm, velázquez kt, et al. influence of dietary saturated fat content on adiposity, macrophage behavior, inflammation, and metabolism: composition matters. j lipid res. 2013;54(1):152-163. doi:10.1194/jlr.m030700 16. binger kj, gebhardt m, heinig m, et al. high salt reduces the activation of il-4– and il-13– stimulated macrophages. journal of clinical investigation. 2015;125(11):4223-4238. doi:10.1172/jci80919 17. wilck n, matus mg, kearney sm, et al. saltresponsive gut commensal modulates th17 axis and disease. nature. 2017;551(7682):585-589. doi:10.1038/nature24628 18. vendrell j, broch m, vilarrasa n, et al. resistin, adiponectin, ghrelin, leptin, and proinflammatory cytokines: relationships in obesity. obesity research. 2004;12(6):962-971. doi:10.1038/oby.2004.118 19. caër c, rouault c, le roy t, et al. immune cellderived cytokines contribute to obesity-related inflammation, fibrogenesis and metabolic deregulation in human adipose tissue. sci rep. 2017;7(1):3000. doi:10.1038/s41598-017-02660w 20. schrader amr, deckers ie, van der zee hh, boer j, prens ep. hidradenitis suppurativa: a retrospective study of 846 dutch patients to identify factors associated with disease severity. journal of the american academy of dermatology. 2014;71(3):460-467. doi:10.1016/j.jaad.2014.04.001 21. boer j. resolution of hidradenitis suppurativa after weight loss by dietary measures, especially on frictional locations. journal of the european academy of dermatology and venereology. 2016;30(5):895-896. doi:10.1111/jdv.13059 22. kromann c, ibler k, kristiansen v, jemec g. the influence of body weight on the prevalence and severity of hidradenitis suppurativa. acta derm venerol. 2014;94(5):553-557. doi:10.2340/00015555-1800 23. kohorst jj, kimball ab, davis mdp. systemic associations of hidradenitis suppurativa. journal of the american academy of dermatology. 2015;73(5):s27-s35. doi:10.1016/j.jaad.2015.07.055 24. sabat r, chanwangpong a, schneider-burrus s, et al. increased prevalence of metabolic syndrome in patients with acne inversa. bruggemann h, ed. plos one. 2012;7(2):e31810. doi:10.1371/journal.pone.0031810 25. kouris a, platsidaki e, christodoulou c, et al. quality of life and psychosocial implications in patients with hidradenitis suppurativa. dermatology. 2016;232(6):687-691. doi:10.1159/000453355 26. riis p, vinding g, ring h, jemec g. disutility in patients with hidradenitis suppurativa: a crosssectional study using euroqol-5d. acta dermato venereologica. 2016;96(2):222-226. doi:10.2340/00015555-2129 27. barrea l, fabbrocini g, annunziata g, et al. role of nutrition and adherence to the mediterranean diet in the multidisciplinary approach of hidradenitis suppurativa: evaluation of nutritional status and its association with severity of disease. nutrients. 2019;11(1):57. doi:10.3390/nu11010057 28. cannistrà c, finocchi v, trivisonno a, tambasco d. new perspectives in the treatment of hidradenitis suppurativa: surgery and brewer’s yeast–exclusion diet. surgery. 2013;154(5):11261130. doi:10.1016/j.surg.2013.04.018 29. mahan lk, escott-stump s, raymond jl, krause mv. krause’s food & the nutrition care process e-book. vol thirteenth edition. saunders; 2012. http://ezproxy.library.arizona.edu/login?url=https:/ /search.ebscohost.com/login.aspx?direct=true&d b=nlebk&an=1167175&site=ehost-live 30. pronsky zm, crowe jp. food medication interactions, 16th edition. journal of pharmacy technology. 2010;26(6):391-392. doi:10.1177/875512251002600616 skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 249 31. pereira ma, jacobs dr, pins jj, et al. effect of whole grains on insulin sensitivity in overweight hyperinsulinemic adults. the american journal of clinical nutrition. 2002;75(5):848-855. doi:10.1093/ajcn/75.5.848 32. u.s. department of health and human services and u.s. department of agriculture. 2015-2020 dietary guidelines for americans. 2015;8th edition:144. 33. dinu m, pagliai g, casini a, sofi f. mediterranean diet and multiple health outcomes: an umbrella review of meta-analyses of observational studies and randomised trials. eur j clin nutr. 2018;72(1):30-43. doi:10.1038/ejcn.2017.58 34. u.s department of agriculture, food and nutrition service. supplemental nutrition assistance program (snap). published online accessed 18-dec-19. https://www.fns.usda.gov/snap/supplementalnutrition-assistance-program 35. mcmillan k. hidradenitis suppurativa: number of diagnosed patients, demographic characteristics, and treatment patterns in the united states. american journal of epidemiology. 2014;179(12):1477-1483. doi:10.1093/aje/kwu078 36. ellis e. rdns and medical nutrition therapy services. eatright.org. published october 8, 2018. accessed february 29, 2020. https://www.eatright.org/food/resources/learnmore-about-rdns/rdns-and-medical-nutritiontherapy-services 37. academy of nutrition and dietetics. medicaid and rdns. eatright.org. https://www.eatrightpro.org/payment/nutritionservices/medicaid/medicaid-and-rdns skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 166 covid concepts herpes zoster post-covid-19 vaccination in young adults (under 35) case series sophie guénin msc1,2, emily elbogen pa2, mindy kresch bs2, mark lebwohl md2 1 new york medical college, valhalla, ny 2 department of dermatology, icahn school of medicine at mount sinai hospital, new york, ny within the last six months, there have been growing reports of herpes zoster (hz) or shingles after vaccination with both pfizer bnt162b2 and moderna mrna-1273 vaccines1,2,3,4,5. hz is caused by the varicellazoster virus (vzv) that typically infects in childhood and remains dormant in ganglionic neurons, indefinitely . vzv is a humanspecific herpesvirus that targets neurons, t lymphocytes, and epithelial cells6. primary infection causes chickenpox and reactivation, later in life, causes hz6. reactivation of vzv commonly produces a characteristic painful, erythematous, vesicular rash in a dermatomal distribution6. the lesion is often followed by post-herpetic neuralgia, a type of neuropathic pain lasting months after rash resolution6. less commonly, hz may also lead to life-threatening conditions such as meningoencephalitis, vasculopathies, and infection6. a systematic review, of all reported cases to date, demonstrated that the mean age of covid-19-vaccine associated hz was 62 years of age, with the majority of patients being over the age of 607. in addition, hz was reported more frequently with first dose vaccinations and with a delay of 3 to 9 days post-injection6. while these associations may be largely coincidental and causality remains to be demonstrated, we present four cases of hz in healthy, young adults under the age of 35 who received either the bnt162b2 or mrna-1273 vaccine. these cases illustrate that hz does not only affect those over the age of 60 post-vaccination, but also those with no known risk factors. however, it is very important to emphasize that these cases do not establish association. our goal is to call for closer investigation given the anecdotal increase in hz cases seen in our vaccinated patients. abstract an increasing number of reports have indicated correlation between covid-19 vaccination and herpes zoster. while these outbreaks may be largely coincidental, the correlation warrants further investigation. herein, we present 4 cases of herpes zoster in young healthy adults with no known risk factors for varicella virus reactivation. to date, most zoster outbreaks have been in patients above 60 years old. thus, we believe that these cases point to a need for increased research on the topic. introduction case series skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 167 case 1. a healthy 27-year-old female with polycystic ovarian syndrome (pcos), received her second dose of bnt162b2 vaccine in her left arm. thirty days later, a group of itchy, painful erythematous papules and vesicles erupted on the right shoulder in the c6 dermatomal distribution (figure 1). there was history of past varicella infection as a child, but no history of previous hz. seven days of valacyclovir was administered and resulted in complete resolution of lesion three weeks later. figure 1. clustered, erythematous vesicles on right shoulder case 2. a healthy 20-year-old male with a past medical history of asthma presented with hz six days after receiving his second injection of the bnt162b2 vaccine in his left arm. the lesion appeared in the t10 dermatomal distribution on the left abdomen (figure 2). there was history of past varicella immunization during childhood. the patient’s lesion resolved after 10 days of valacyclovir treatment. figure 2. herpes zoster in t10 dermatomal distribution in 20-year-old male case 3. a healthy 32-year-old female with a history of nephrolithiasis presented with hz 28 days post-vaccination with second dose of the mrna-1273 vaccine in her left arm. the lesion was located over the right breast in a t4 dermatomal distribution. there was history of childhood infection of varicella, but no history of prior hz. the patient’s lesion resolved after 10 days of valacyclovir treatment. case 4. a healthy 27-year-old female with no significant past medical history presented with hz 39 days after second dose of the mrna-1273 vaccine in her right arm. the lesion was located on her left arm in a t1 distribution. there was a history of childhood infection of varicella, but no history of prior hz. the patient’s lesion resolved after 10 days of valacyclovir treatment. our case series demonstrates a potential correlation between covid-19 vaccination and hz in individuals with no reactivation risk factors. in three of the presented cases, reactivation of the virus occurred about a month after injection compared to the 3-to-9day delay previously reported7. varicella reactivation presented 6 days subsequent to covid-19 vaccination in a varicella immunized patient, indicating likely reactivation of the oka strain varicella zoster virus (okavzv). in addition, all four hz cases were associated with second dose vaccination unlike previous reports demonstrating association more frequently with first-doses7. these differences may indicate a different reactivation mechanism between the two groups or support mere coincidence. discussion skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 168 the precise mechanism leading to maintenance of vzv latency and reactivation remains highly controversial and poorly understood6. however, it is largely believed that hz occurs in response to a decline in cell-mediated immunity as a result of aging or immunocompromised states6. bnt162b1 and mrna-1273 vaccines direct synthesis of the sars-cov-2 spike (s) protein, which is recognized by antigenpresenting cells and elicits a predominantly type 1 helper t (th1) cell response8,9. the mrna-1273 vaccine was shown to elicit strong release of tnf-α, il-2, and inf-γ in individuals aged 56 to 70 years7. cytokine levels were highest after about 1-month postinjection, which would coincide with the hz cases in three of our young adults7. the increase in cytokine expression and th1 cell response may effectively disrupt immune cell homeostasis leading to vzv evasion of the innate immune system and subsequent reactivation. however, this would not be unique to the covid-19 vaccines as hz has also been reported after hepatitis a, influenza, rabies, and japanese encephalitis vaccination10. others have hypothesized that the transient lymphopenia seen in 45.5% of individuals receiving bnt162b1 may explain hz incidence11. apparent lymphopenia may be caused by the surge in type i interferons that regulate lymphocyte extravasation from circulation12. interestingly, biopsied hz lesions are depleted of langerhans cells that help modulate the skin’s innate immunity13. thus, while functionally, the immune system is intact, lymphocytes may not be able to localize to the skin and maintain vzv latency. some other contributing factors that may explain hz post-vaccination may include pandemic or vaccine-related emotional and physical stress, which could lead to a spike in cortisol, a known immunosuppressant. lastly, we must also acknowledge the variety of confounding factors in reported hz cases during the pandemic. the pandemic and constant focus on health may have led to some patients having a lower threshold for calling their physicians leading to an increase in reported hz cases. at the same time, other patients may have chosen to avoid healthcare spaces for fear of covid-19 infection leading to possibly underreported hz cases. taken together, these reports of hz subsequent to bnt162b1 and mrna-1273 vaccination warrant further studies in controlled environments to either establish coincidence or association. these future studies will be especially important in counseling patients prior to covid-19 booster vaccines. conflict of interest disclosures: mark lebwohl is an employee of mount sinai and receives research funds from: abbvie, amgen, arcutis, avotres, boehringer ingelheim, dermavant sciences, eli lilly, incyte, janssen research & development, llc, ortho dermatologics, regeneron, and ucb, inc., and is a consultant for aditum bio, almirall, altrubio inc., anaptysbio, arcutis, inc., aristea therapeutics, arrive technologies, avotres therapeutics, biomx, boehringer-ingelheim, bristol-myers squibb, cara therapeutics, castle biosciences, corrona, dermavant sciences, dr. reddy’s laboratories, evelo biosciences, evommune, inc., facilitation of international dermatology education, forte biosciences, foundation for research and education in dermatology, helsinn therapeutics, hexima ltd., leo pharma, meiji seika pharma, mindera, pfizer, seanergy, and verrica. authors guénin, kresch, and elbogen have no conflicts of interest to declare. funding: none corresponding author: sophie guénin, msc department of dermatology icahn school of medicine at mount sinai hospital 5 east 98th street, 5th floor conclusion skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 169 new york, ny 10029 email: sophiehelene.guenin@gmail.com references: 1. lee, c., cotter, d., basa, j., & greenberg, h. l. (2021). post covid‐19 vaccine related shingles cases seen at the las vegas dermatology clinic and sent to us via social media. journal of cosmetic dermatology. 2. channa, l., torre, k., & rothe, m. (2021). herpes zoster reactivation after mrna-1273 (moderna) sars-cov-2 vaccination. jaad case reports, 15, 60-61. 3. eid, e., abdullah, l., kurban, m., & abbas, o. (2021). herpes zoster emergence following mrna covid‐19 vaccine. journal of medical virology. 4. bostan, e., & yalici-armagan, b. (2021). herpes zoster following inactivated covid-19 vaccine: a coexistence or coincidence?. journal of cosmetic dermatology. 5. lladó, i., fernández-bernáldez, a., & rodríguez-jiménez, p. (2021). varicella zoster virus reactivation and mrna vaccines as a trigger. jaad case reports, 15, 62-63. 6. gershon, a. a., breuer, j., cohen, j. i., cohrs, r. j., gershon, m. d., gilden, d., ... & yamanishi, k. (2015). varicella zoster virus infection. nature reviews disease primers, 1(1), 1-18. 7. katsikas triantafyllidis, k., giannos, p., mian, i. t., kyrtsonis, g., & kechagias, k. s. (2021). varicella zoster virus reactivation following covid-19 vaccination: a systematic review of case reports. vaccines, 9(9), 1013. 8. anderson, e. j., rouphael, n. g., widge, a. t., jackson, l. a., roberts, p. c., makhene, m., ... & beigel, j. h. (2020). safety and immunogenicity of sars-cov-2 mrna-1273 vaccine in older adults. new england journal of medicine, 383(25), 2427-2438. 9. sahin, u., muik, a., derhovanessian, e., vogler, i., kranz, l. m., vormehr, m., ... & türeci, ö. (2020). covid-19 vaccine bnt162b1 elicits human antibody and th 1 t cell responses. nature, 586(7830), 594-599. 10. walter, r., hartmann, k., fleisch, f., reinhart, w. h., & kuhn, m. (1999). reactivation of herpesvirus infections after vaccinations?. the lancet, 353(9155), 810. 11. mulligan, m. j., lyke, k. e., kitchin, n., absalon, j., gurtman, a., lockhart, s., ... & jansen, k. u. (2020). phase i/ii study of covid-19 rna vaccine bnt162b1 in adults. nature, 586(7830), 589-593. 12. kamphuis, e., junt, t., waibler, z., forster, r., & kalinke, u. (2006). type i interferons directly regulate lymphocyte recirculation and cause transient blood lymphopenia. blood, 108(10), 3253-3261. 13. laing, k. j., ouwendijk, w. j., koelle, d. m., & verjans, g. m. (2018). immunobiology of varicella-zoster virus infection. the journal of infectious diseases, 218(suppl_2), s68-s74. mailto:sophiehelene.guenin@gmail.com powerpoint presentation presented at 2021 fall clinical dermatology conference, las vegas, nv, usa, october 21–24, 2021 roflumilast cream 0.3% improved the severity and impact of itch in patients with chronic plaque psoriasis in the phase 3 dermis-1 and dermis-2 studies efficacy • both phase 3 studies met the primary endpoint of iga success at week 8 (figure 2) – significantly greater percentages of roflumilast-treated patients achieved iga success with roflumilast than with vehicle (figure 2) • least squares (ls) mean change from baseline in wi-nrs was significantly greater with roflumilast cream (figure 3) • significantly greater percentages of roflumilast-treated patients achieved ≥4-point reduction in wi-nrs at week 8 (figure 4) • roflumilast cream reduced the patient-reported severity of itch (figure 5) • roflumilast cream significantly reduced patient-reported burden of itch at all timepoints (figure 6) • roflumilast cream improved patient quality of life as indicated by changes in dlqi (figure 7) conclusions • once-daily treatment with roflumilast cream 0.3% provided significant, consistent, and sustained improvements in the severity and burden of itch and quality of life in patients with chronic plaque psoriasis – onset of action of patient-reported improvements were observed as early as the first timepoint measured (2 weeks) and improvement continued through week 8 – results were reproducible across both phase 3 studies • roflumilast cream was associated with low rates of application-site aes, treatment-related aes, and discontinuations due to aes • dermis-1 and dermis-2 support the potential use of investigational roflumilast cream as an effective and well-tolerated nonsteroidal topical therapy in patients with chronic plaque psoriasis melinda j. gooderham,1 javier alonso-llamazares,2 jerry bagel,3 john c. browning,4 zoe d. draelos,5 kimberly k. grande,6 adelaide a. hebert,7 h. chih-ho hong,8 mark lebwohl,9 wei jing loo,10 walter k. nahm,11 kim a. papp, 12 david m. pariser,13 jennifer soung,14 linda stein gold,15 irina turchin,16 amy feng,17 patrick burnett,17 robert c. higham,17 david r. berk17 1skin centre for dermatology, probity medical research and queen’s university, peterborough, on, canada; 2driven research llc, coral gables, fl, usa; 3psoriasis treatment center of central new jersey, windsor, nj, usa; 4texas dermatology and laser specialists, san antonio, tx, usa; 5dermatology consulting services, high point, nc, usa; 6the skin wellness center, p.c., knoxville, tn, usa; 7ut health mcgovern medical school, houston, tx, usa; 8probity medical research and department of dermatology and skin science, university of british columbia, surrey, bc, canada; 9icahn school of medicine at mount sinai, new york, ny, usa; 10dermeffects and probity medical research, london, on, canada; 11university of california, san diego, school of medicine, la jolla, ca, usa; 12probity medical research and k papp clinical research, waterloo, on, canada; 13eastern virginia medical school and virginia clinical research, inc., norfolk, va, usa; 14southern california dermatology, santa ana, ca, usa; 15henry ford medical center, detroit, mi, usa; 16brunswick dermatology center, fredericton, nb, canada and probity medical research; 17arcutis biotherapeutics, inc., westlake village, ca, usa references 1. elewski b, et al. j eur acad dermatol venereol 2019;33:1465-1476. 2. globe d, et al. health qual life outcomes 2009;7:62. 3. lebwohl mg, et al. n engl j med 2020;383:229-239. 4. lebwohl mg, et al. 2021 european academy of dermatology and venereology spring symposium, sept 29–oct 2, 2021. acknowledgements • this study was supported by arcutis biotherapeutics, inc. • thank you to the investigators and their staff for their participation in the trial • we are grateful to the study participants and their families for their time and commitment • writing support was provided by christina mcmanus, phd, alligent biopharm consulting llc, and funded by arcutis biotherapeutics, inc. disclosures mjg, ja-l, jb, jcb, zdd, kkg, aah, hch, ml, wjl, wkn, kap, dmp, js, lsg, and it are investigators and/or consultants for arcutis biotherapeutics, inc. and received grants/research funding and/or honoraria; af, pb, rch, and drb are employees of arcutis biotherapeutics, inc. additional disclosures provided on request. introduction • itch is the most burdensome and frequently reported symptom of psoriasis1,2 • roflumilast is a selective and highly potent phosphodiesterase-4 inhibitor being investigated as a once-daily, nonsteroidal, topical treatment for various dermatologic conditions – roflumilast cream provided significant and rapid improvement of patients with psoriasis, including improving intertriginous plaques and reducing itch, in a phase 2b and 2 randomized phase 3, double-blind, vehicle-controlled trials3,4 • here we report the results of patient-reported outcomes, including itch, from the dermis-1 and dermis-2 phase 3 trials methods • dermis-1 and dermis-2 were identical randomized, multicenter, parallel-group, double-blind, vehicle-controlled studies (figure 1) • patients eligible for inclusion in the dermis-1 and dermis-2 studies were ≥2 years old with psoriasis on the face, extremities, trunk, and/or intertriginous areas involving 2% to 20% of body surface area (bsa), not including the scalp, palms, or soles; investigator global assessment (iga) score of at least mild at baseline; and a baseline psoriasis area and severity index (pasi) score ≥2 • patients were randomized 2:1 to receive once-daily (qd) roflumilast cream 0.3% or vehicle cream • the primary efficacy endpoint for both studies was iga success (defined as achievement of clear or almost clear status plus a ≥2-grade improvement from baseline) at week 8 – secondary efficacy endpoints included ≥4-point reduction on the worst itch-numeric rating scale (wi-nrs success; determined in patients ≥12 years with wi-nrs score ≥4 at baseline), change in psoriasis symptom diary item 1 (severity of itch), change in psoriasis symptom diary item 2 (burden of itch), and change in dermatology life quality index (dlqi) • the primary endpoint was analyzed using a cochran-mantel-haenszel test stratified by site, baseline iga, and baseline intertriginous involvement – statistical significance was concluded at the 5% significance level (2-sided) – missing iga scores were imputed using multiple imputation • to control for multiple comparisons among the secondary endpoints, a multiplicity procedure was used – upon successful testing of the primary endpoint, the α was partitioned to test secondary endpoints results • 439 patients were enrolled in dermis-1 and 442 patients were enrolled in dermis-2 • most patients (86.2% to 91.0%) completed the studies (table 1) – few patients discontinued due to adverse events (aes) • baseline disease characteristics were balanced across treatment groups and similar between the 2 studies (table 2) safety • safety and tolerability of roflumilast cream were similar to vehicle (table 3) • roflumilast cream demonstrated low rates of application-site aes, treatment-related aes, and discontinuations due to aes (table 3) – rates were comparable with vehicle • there were no treatment-related serious aes • application-site reactions were low • over 96% of patients in each group had no evidence of irritation at week 4 or 8 as assessed by the investigators table 2. baseline disease characteristics (itt population) dermis-1 dermis-2 roflumilast cream 0.3% (n=286) vehicle (n=153) roflumilast cream 0.3% (n=290) vehicle (n=152) psoriasis-affected bsa, mean % (sd) 6.3 (4.38) 7.4 (4.76) 7.1 (4.84) 7.7 (5.05) iga score, n (%) 2 (mild) 51 (17.8) 20 (13.1) 50 (17.2) 24 (15.8) 3 (moderate) 206 (72.0) 122 (79.7) 220 (75.9) 118 (77.6) 4 (severe) 29 (10.1) 11 (7.2) 20 (6.9) 10 (6.6) pasi, mean score (sd) 6.3 (3.15) 6.8 (3.70) 6.5 (3.22) 7.0 (3.52) wi-nrs, mean score (sd) 5.7 (2.75) 5.7 (2.84) 5.8 (2.61) 6.1 (2.75) wi-nrs score ≥4, n (%) 218 (76.2) 115 (75.2) 229 (79.0) 116 (76.3) psd total score, mean (sd) 72.1 (42.75) 73.4 (41.29) 69.3 (40.66) 77.4 (41.24) psd item 1: severity of itch, mean (sd) 5.5 (2.89) 5.6 (2.88) 5.6 (2.74) 6.0 (2.88) psd item 2: burden of itch, mean (sd) 5.4 (2.97) 5.3 (2.98) 5.4 (2.89) 6.0 (3.02) dlqi, mean score (sd) 7.4 (5.69) 7.0 (5.04) 6.9 (5.51) 7.8 (5.74) bsa: body surface area; dlqi: dermatology life quality index; iga: investigator global assessment; itt: intent-to-treat; pasi: psoriasis area severity index; psd: psoriasis symptoms diary; sd: standard deviation; wi-nrs: worst itch-numeric rating scale. bsa: body surface area; dlqi: dermatology life quality index; iga: investigator global assessment; pasi: psoriasis area and severity index; psd: psoriasis symptom diary; qd: once daily; wi-nrs: worst itch-numeric rating scale. figure 1. study design endpoints primary • iga success at week 8 secondary included (weeks 2, 4, 6, and 8) • wi-nrs • psd item 1 (severity of itch) • psd item 2 (burden of itch) • dlqi safety and tolerability 8 weeks dosing visits: weeks 2, 4, 8 eligibility • diagnosis of plaque psoriasis for ≥6 months (3 months for children) • age 2+ • iga of at least mild severity • 2–20% bsa • pasi ≥2 roflumilast cream 0.3% qd vehicle cream qd ra nd om iz e 2:1 n=400+ dermis-1 n=439 nct04211363 dermis-2 n=442 nct04211389 randomized, double-blind, vehicle-controlled, multicenter studies (2 identical, parallel-group, phase 3 studies) table 1. patient disposition dermis-1 dermis-2 patients, n (%) roflumilast cream 0.3% (n=286) vehicle (n=153) roflumilast cream 0.3% (n=290) vehicle (n=152) completed 255 (89.2) 133 (86.9) 264 (91.0) 131 (86.2) prematurely discontinued 31 (10.8) 20 (13.1) 26 (9.0) 21 (13.8) reason for discontinuation withdrawal by patient 11 (3.8) 11 (7.2) 10 (3.4) 11 (7.2) physician decision 0 1 (0.7) 0 0 noncompliance 0 0 0 1 (0.7) protocol violation 1 (0.3) 0 0 0 lost to follow-up 12 (4.2) 4 (2.6) 15 (5.2) 7 (4.6) adverse event 5 (1.7) 2 (1.3) 1 (0.3) 2 (1.3) pregnancy 1 (0.3) 0 0 0 other 1 (0.3) 2 (1.3) 0 0 wi-nrs scale: 0 (no itch) to 10 (worst imaginable itch). evaluated in the intent-to-treat population of patients; analysis of covariance with treatment, site, baseline iga, baseline intertriginous involvement, and baseline wi-nrs score as independent variables. iga: investigator global assessment; ls: least squares; se: standard error; wi-nrs: worst itchnumeric rating scale. figure 3. ls mean change from baseline in wi-nrs in dermis-1 and dermis-2 the primary endpoint was achieved in both dermis-1 and dermis-2 (week 8) analyzed using a cochran-mantel-haenszel test stratified by site, baseline iga, and baseline intertriginous involvement; 95% ci obtained using the wilson method; missing scores imputed using multiple imputations. intent-to-treat population. ci: confidence interval; iga: investigator global assessment. figure 2. percentages of patients with iga success in dermis-1 and dermis-2 iga success = clear or almost clear plus ≥2-grade improvement from baseline ls mean change from baseline in wi-nrs: patient’s assessment of worst itch over the past 24 hours improvements in ls mean change from baseline with roflumilast cream occurred as early as week 2 (first timepoint evaluated) -2.3 -2.9 -3.6 -3.7 -1.0 -1.2 -1.4 -1.4 -5 -4 -3 -2 -1 0 baseline week 2 week 4 week 6 week 8 ls m ea n ch an ge f ro m b as el in e (s e) roflumilast 0.3% (n=286) vehicle (n=153) *** *** *** baseline mean (sd) wi-nrs: roflumilast 0.3%: 5.7 (2.75) vehicle: 5.7 (2.84) -2.6 -3.0 -3.7 -4.0 -1.2 -0.9 -1.7 -1.7 -5 -4 -3 -2 -1 0 baseline week 2 week 4 week 6 week 8 ls m ea n ch an ge f ro m b as el in e (s e) roflumilast 0.3% (n=290) vehicle (n=152) *** *** *** baseline mean (sd) wi-nrs: roflumilast 0.3%: 5.8 (2.61) vehicle: 6.1 (2.75) *** dermis-1 dermis-2 ***p<0.0001 *** table 3. adverse events dermis-1 dermis-2 n (%) roflumilast cream 0.3% (n=286) vehicle (n=153) roflumilast cream 0.3% (n=290) vehicle (n=152) patients with any teae 72 (25.2) 36 (23.5) 75 (25.9) 28 (18.4) patients with any treatment-related teae 7 (2.4) 3 (2.0) 16 (5.5) 8 (5.3) patients with any serious ae 2 (0.7) 1 (0.7) 0 1 (0.7) patients who discontinued study due to ae 5 (1.7) 2 (1.3) 1 (0.3) 2 (1.3) most common teae (>2% in any group), preferred term hypertensiona 5 (1.7) 6 (3.9) 4 (1.4) 0 headache 3 (1.0) 2 (1.3) 11 (3.8) 1 (0.7) diarrhea 10 (3.5) 0 8 (2.8) 0 psoriasis 0 3 (2.0) 1 (0.3) 0 nasopharyngitis 5 (1.7) 3 (2.0) 1 (0.3) 1 (0.7) ahypertension includes synonymous terms (eg, blood pressure increased). data are presented for safety population. ae: adverse event; teae: treatment-emergent adverse event. these two phase 3 studies demonstrate roflumilast cream, an investigational once-daily, nonsteroidal topical phosphodiesterase-4 inhibitor, was effective in reducing itch, which decreased disease burden and improved quality of life in patients with chronic plaque psoriasis evaluated in the intent-to-treat population; analysis of covariance with treatment, site, baseline iga, baseline intertriginous involvement, and baseline psd score as independent variables. iga: investigator global assessment; ls: least squares; psd: psoriasis symptom diary; se: standard error; wi-nrs: worst itch-numeric rating scale. figure 5. ls mean percentage change from baseline in psd item 1 (severity of itch) evaluated in the intent-to-treat population; analysis of covariance with treatment, site, baseline iga, baseline intertriginous involvement, and baseline psd score as independent variables. iga: investigator global assessment; ls: least squares; psd: psoriasis symptom diary; se: standard error; wi-nrs: worst itch-numeric rating scale. figure 6. ls mean percentage change from baseline in psd item 2 (bother of itch) wi-nrs scale: 0 (no itch) to 10 (worst imaginable itch). evaluated in a subset of the intent-to-treat population of patients with wi-nrs pruritus score ≥4 at baseline using a cochranmantel-haenszel test stratified by site, baseline iga, and baseline intertriginous involvement; missing scores imputed using multiple imputations; 95% ci obtained using the wilson method. ci: confidence interval; wi-nrs: worst itch-numeric rating scale. figure 4. percentages of patients achieving ≥4-point reduction in wi-nrs figure 7. ls mean percentage change from baseline in dlqi evaluated in the intent-to-treat population; analysis of covariance with treatment, site, baseline iga, baseline intertriginous involvement, and baseline dlqi score as independent variables. dlqi: dermatology life quality index; iga: investigator global assessment; ls: least squares; sd: standard deviation; se: standard error; wi-nrs: worst itch-numeric rating scale. 0.0 -27.4 -51.2 -65.2 -2.4 -16.8 -12.7 -100 -90 -80 -70 -60 -50 -40 -30 -20 -10 0 10 20 30 baseline week 2 week 4 week 6 week 8 ls m ea n % c ha ng e fr om b as el in e (s e) roflumilast 0.3% (n=286) vehicle (n=153) ** *** baseline mean (sd) dlqi score: roflumilast 0.3%: 7.4 (5.69) vehicle: 7.0 (5.04) dermis-1 *** ls mean change from baseline in wi-nrs: patient’s assessment of worst itch over the past 24 hours ls mean change from baseline in dlqi total scores favored roflumilast over vehicle across both studies -36.6 -46.8 -69.4 15.0 -2.9 -9.0 -100 -90 -80 -70 -60 -50 -40 -30 -20 -10 0 10 20 30 baseline week 2 week 4 week 6 week 8 ls m ea n % c ha ng e fr om b as el in e (s e) roflumilast 0.3% (n=290) vehicle (n=152) *** *** baseline mean (sd) dlqi score: roflumilast 0.3%: 6.9 (5.51) vehicle: 7.8 (5.74) *** dermis-2 **p<0.01; ***p<0.0001 ls mean percentage change from baseline in psd item 2: how bothered were you by your psoriasis-related itching over the past 24 hours? significantly greater improvements in burden of itch were observed with roflumilast cream in both studies -42.8 -59.7 -70.1 -71.6 -14.9 -12.5 -14.3 -13.8 -100 -90 -80 -70 -60 -50 -40 -30 -20 -10 0 baseline week 2 week 4 week 6 week 8 ls m ea n % c ha ng e fr om b as el in e (s e) roflumilast 0.3% (n=286) vehicle (n=153) *** *** *** -43.9 -63.6 -65.4 -71.8 -15.5 -19.0 -22.6 -28.7 -100 -90 -80 -70 -60 -50 -40 -30 -20 -10 0 baseline week 2 week 4 week 6 week 8 ls m ea n % c ha ng e fr om b as el in e (s e) roflumilast 0.3% (n=290) vehicle (n=152) *** *** *** *** dermis-1 dermis-2 ***p<0.0001 *** ls mean percentage change from baseline in psd item 1: how severe was your psoriasis-related itching over the past 24 hours? significantly greater improvements in itch severity were observed with roflumilast cream in both studies -42.7 -55.2 -67.3 -72.5 -11.1 -18.2 -18.8 -21.5 -100 -90 -80 -70 -60 -50 -40 -30 -20 -10 0 baseline week 2 week 4 week 6 week 8 ls m ea n % c ha ng e fr om b as el in e (s e) roflumilast 0.3% (n=286) vehicle (n=153) *** *** *** -48.9 -60.4 -65.0 -70.5 -18.8 -13.9 -22.6 -26.9 -100 -90 -80 -70 -60 -50 -40 -30 -20 -10 0 baseline week 2 week 4 week 6 week 8 ls m ea n % c ha ng e fr om b as el in e (s e) roflumilast 0.3% (n=290) vehicle (n=152) *** *** *** *** dermis-1 dermis-2 ***p<0.0001 *** among patients with baseline wi-nrs score ≥4, more than two-thirds of roflumilast-treated patients achieved ≥4-point reduction in wi-nrs proportion of patients who achieved a ≥4-point improvement in wi-nrs from baseline score of ≥4: patient’s assessment of worst itch over the past 24 hours 34.9 50.2 57.8 67.5 22.0 18.0 22.2 26.8 0 10 20 30 40 50 60 70 80 90 100 week 2 week 4 week 6 week 8 % o f p at ie nt s (9 5% c i) roflumilast 0.3% (n=218) vehicle (n=115) *** *** *** 41.9 56.6 62.0 69.4 21.1 21.9 30.6 35.6 0 10 20 30 40 50 60 70 80 90 100 week 2 week 4 week 6 week 8 % o f p at ie nt s (9 5% c i) roflumilast 0.3% (n=229) vehicle (n=116) *** *** *** ** dermis-1 dermis-2 **p<0.01; ***p<0.0001 5.9% 20.6% 33.3% 42.4% 2.1% 2.3% 6.1% 6.1% week 2 week 4 week 6 week 8 roflumilast 0.3% (n=286) vehicle (n=153) 3.3% 19.1% 25.6% 37.5% 2.1% 5.8% 4.7% 6.9% week 2 week 4 week 6 week 8 roflumilast 0.3% (n=290) vehicle (n=152) *** * *** *** *** *** iga success dermis-1 iga success dermis-2 *p<0.05; **p<0.01; ***p<0.0001 ** 0 10 20 30 70 80 90 100 40 50 60 % o f pa ti en ts (9 5% c i) 0 10 20 30 70 80 90 100 40 50 60 % o f pa ti en ts (9 5% c i) roflumilast cream 0.3% improved the severity and impact of itch in patients with chronic plaque psoriasis �in the phase 3 dermis-1 and dermis-2 studies << /ascii85encodepages false /allowtransparency false /autopositionepsfiles true /autorotatepages /none /binding /left /calgrayprofile (gray gamma 2.2) /calrgbprofile (srgb iec61966-2.1) /calcmykprofile (u.s. web coated \050swop\051 v2) /srgbprofile (srgb iec61966-2.1) /cannotembedfontpolicy /warning /compatibilitylevel 1.4 /compressobjects /tags /compresspages false /convertimagestoindexed true /passthroughjpegimages true /createjobticket false /defaultrenderingintent 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/usehtmltitleasmetadata true >> ] >> setdistillerparams << /hwresolution [2400 2400] /pagesize [612.000 792.000] >> setpagedevice acknowledgements study funded by galderma r&d; poster/editorial support provided by galderma laboratories, l.p.  introduction rosacea affects over 16 million americans and is characterized by highly reactive skin  with flares commonly induced by normally benign external stimuli. while cleansing  and moisturizing is paramount to helping to maintain healthy skin, many skincare  formulations may be formulated with ingredients that are irritating to rosacea skin.  common  irritants  and  triggers  include  organic uv  filters,  fragrances,  and harsh  surfactants among others. a broad spectrum spf 20 facial moisturizer (cetaphil daily  facial moisturizer with broad spectrum spf 20 [dfm]) was developed specifically for  patients with redness­prone skin. this formula contains inorganic uv filters to protect  against irritation and sun damage and a neutral tint to improve the appearance of  facial erythema. additionally it is also formulated with allantoin, caffeine, licorice  root extract, and vitamin e to help calm and soothe rosacea­prone skin. this poster  presents the results of two clinical studies that assessed the performance and tolerability  of dfm. tolerability and efficacy of a moisturizing broad spectrum sunscreen formulated for redness­prone skin matthew h meckfessel, phd1; sandrine teissedre, msc2; nadege lachmann3; francine santoro, md3  1galderma laboratories, l.p., fort worth, texas; 2galderma r&d, sophia antipolis, france; 3galderma r&d, egerkingen, switzerland cet.p­rd105649­01 summary dfm significantly improves skin hydration and skin barrier  function and is an ideal daily broad spectrum facial moisturizer  for patients with rosacea and sensitive skin subjects and methods study 1: hydration and skin barrier function  • men and women with dry volar forearms • inner forearms randomized to treated and control • 40 mg of product applied to 20 cm2  ­ corneometer and transepidermal water loss (tewl) assessed at baseline and 2, 4, 8, and 24 hours study 2: in use efficacy and tolerability • men or women with rosacea and mild to moderate non­transient erythema • product applied qd in the morning for 3 weeks • assessments made on day 1 before application, day 1 30 minutes after first use and days 3, 8, and 22 before product application  ­ objective (chromameter) and subjective (investigator and subject) assessment of redness  ­ investigator and subject tolerability assessments · redness and tolerability assessments made on a 5 point scale of 0 (none), 0.5 (very slight), 1 (slight), 2 (moderate) and 3 (strong)  ­ subject satisfaction m ea n  sc or e baseline 30 minutes dryness tightness 0 0.1 0.7 0.2 0.5 1 2 3 *p < .05 vs baseline * * disagree neutral agree percent of subjects overall, i like the product very much easy to apply suitable for sensitive skin neutralizes the look of redness 0 100 12020 40 60 80 0 96.7 73.3 23.3 3.3 3.3 70.0 90.0 6.7 6.7 6.7 20.0 p < .05 for agree vs disagree for all figure 4. subject assessment of dryness and tightness (n=30) figure 5. subject satisfaction (n=30) figure 1. investigator assessments figure 2. investigator and subject assessed facial redness (n=30) figure 3. investigator and subject assessments m ea n  co rn eo m et er  (a .u .) dfm control area hour 0 20 22 24 26 28 30 32 34 36 38 40 4 8 12 16 20 24 * * * *p < .05 vs baseline m ea n  sc or e investigator subject baseline 0 1 2 3 day 3 day 8 day 22 dfm control area *p < .05 vs baseline * * * * m ea n  te w l  (g /m 2h ) hour 0 0 2 4 6 8 10 4 8 12 16 20 24 cheek forehead m ea n  sc or e  (a .u ) 0 5 10 15 20 25 *  * * *p < .05 vs baseline baseline day 3 day 8 day 22 m ea n  sc or e baseline 30 minutes investigator 0 0.8 1.2 1.2 1.5 1 2 3 subject *p < .05 vs baseline * * results skin hydration and skin barrier function significantly improved for 8 and 24 hours,  respectively (figure 1). for the in use study, 33 women enrolled with 30 completing the  study (the 3 dropouts were unrelated to the study product); 91% of the subjects also  presented with sensitive skin. the mean age was 53.7 years. investigator and subject  assessed skin redness significantly improved immediately after application (figure 2).  there was no significant worsening of erythema during the study as assessed after  product application (figure 3). skin dryness and feelings of tightness also significantly  improved compared to baseline (figure 4). the product was well tolerated with mean  scores for all parameters less than mild (data not shown). subjects demonstrated high  satisfaction with the product (figure 5). one mild, possibly related adverse event (ae)  of exfoliative and dry small area on the neck was reported. three additional unrelated  aes were also reported: extraction of 3 teeth with anesthesia, stitches removed, and  heartburn. skin hydration skin redness assessments before product application subject feelings of dryness and tightness immediately  before and after application assessment of redness before and after first application skin barrier function chromameter redness assessments a a bb fc17postergaldermameckfesselbroadspectrumtolerability.pdf skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 243 brief article coexistent of morphea and dle in a patient with beta thalassemia leading to a diagnosis of systemic lupus erythematous marilyn le, ms1, payvand kamrani, do2, l. claire hollins, md2 1 philadelphia college of osteopathic medicine, philadelphia, pa 2 department of dermatology, penn state health milton s. hershey medical center, hershey, pa an 18-year-old female with beta thalassemia presented with a six-month history of rash. physical exam showed two depigmented patches with surrounding hypopigmentation on the left lower back (figure 1), and indurated, annular pink and brown plaques on the scalp (figure 2a) and left temple (figure 2b). two biopsies were performed of the clinically distinct lesions on the scalp and left lower back. histopathology of the scalp demonstrated irregular epithelial acanthosis, perifollicular and band-like lymphocytic infiltrate, thickened basement membrane figure 1. depigmented patches with surrounding hypopigmentation on the left lower back with histology consistent with guttate morphea. zone, slight mucin which was consistent with the diagnosis of discoid lupus erythematous abstract patients with autoimmune disorders are predisposed to developing a second autoimmune condition. this can be applied to cutaneous conditions as well. morphea or localized scleroderma is an autoimmune inflammatory and fibrosing skin disorder due to increased collagen deposition.1,2 patients with morphea are four times likelier of having a concomitant autoimmune disease.1 there have been cases of systemic lupus erythematosus (sle) with morphea, but the co-occurrence of discoid lupus erythematosus (dle) with morphea has been rarely reported, and never reported in patient with betathalamessmia.1,2,7 morphea and discoid lupus erythematosus can be found within one lesion or as separate diagnoses. in this case, we describe a patient with morphea and discoid lupus erythematous in the setting of beta thalassemia leading to diagnosis of sle. introduction case report skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 244 figure 2. indurated light brown plaques a) with localized alopecia of the scalp and b) left temple lupus (figure 3a). the left lower back consisted of sclerotic collagen bundles within the dermis with perivascular interstitial mononuclear cell infiltrate that was consistent with morphea (figure 3b). labs were obtained to evaluate for sle, which were significant for positive ana, antismith antibody, and anti-rnp antibody. she was subsequently diagnosed with sle by rheumatology following the american college of rheumatology (acr) with discoid lupus findings (+4 points) and sle specific antibodies (+6), with a total score of 10, fulfilling the criteria for sle. she was subsequently started on hydroxychloroquine 5 mg/kg and topical augmented betamethasone dipropionate ointment twice daily and educated on sun protective measures. at her three month follow up, she reported no new lesions or progression of her current lesions. overlap syndromes are common in connective tissue diseases.4 there have been few cases of morphea and dle presenting within the same site. mir et al. presented a case of 20-year-old woman with a spreading hypopigmented plaque on her right arm with limited range of motion with biopsy confirming dle and morphea.5 pascucci et al. reported a case of a 60-yearold man with a progressive pruritic rash on the upper back for 30 years with biopsy revealing evidence of coexisting dle and morphea.4 our patient had separate lesions of dle and morphea, with no overlap. to this date, only one other case of dle and morphea in two different sites has been reported. in that case, a 46-year-old woman with history of depression and lithium-induced hypothyroidism was diagnosed with dle for her facial lesions and linear morphea for right axilla.3 furthermore, there have not been any reported cases of dle and morphea in patients with beta thalassemia to our knowledge. there have been reports of patients with beta thalassemia with diagnosed sle. castellino et al. published a case series of 177 patients with sle, and 17 patients had beta thalassemia. their study demonstrated that the prevalence of sle in patients with beta thalassemia was far less when compared to the general population. however, when sle and beta thalassemia coexist, sle seems to be more severe.6,7 the association of sle and beta thalassemia is not fully understood but theories include that the increased need for blood transfusions in beta-thalassemia patients can lead to formation of alloantibodies which can place patients at risk for infections and collagen vascular disorders.8 whether or not having betathalassemia increases the risk of autoimmune skin disorders remain unclear. in conclusion, we report the first case of dle and morphea appearing simultaneously discussion conclusion a. b. skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 245 figure 3. h&e of scalp with perifollicular, band-like lymphocytic interface with vacuolar changes with mucin and follicular plugging (a) and superficial perivascular lymphocytic (b) consistent with the diagnosis of cutaneous lupus. in a patient with beta-thalassemia leading to a diagnosis of sle. an association with sle with beta thalassemia has been studied, however the extent with autoimmune skin conditions remains unknown. conflict of interest disclosures: none funding: none corresponding author: payvand kamrani, do penn state health milton s. hershey medical center 500 university drive hershey, pa 17033 phone: 717-531-6820 email: pkamrani@pennstatehealth.psu.edu references: 1. leitenberger jj, cayce rl, haley rw, adams-huet b, bergstresser pr, jacobe ht. distinct autoimmune syndromes in morphea: a review of 245 adult and pediatric cases. arch dermatol. 2009;145(5):545-550. doi:10.1001/archdermatol.2009.79 2. pham ak, srivastava b, deng a. pregnancyassociated morphea: a case report and literature review. dermatol online j. 2017;23(1):13030/qt5qv9f9h3. published 2017 jan 15. 3. bernárdez c, prieto-torres l, macías e, et al. concurrent presentation of cutaneous lesions of deep linear morphoea and discoid lupus erythematosus. lupus. 2016;25(2):204-208. doi:10.1177/0961203315604911 4. pascucci a, lynch pj, fazel n. lupus erythematosus and localized scleroderma coexistent at the same sites: a rare presentation of overlap syndrome of connective-tissue diseases. cutis. 2016;97(5):359-363. 5. mir a, tlougan b, o'reilly k, et al. morphea with discoid lupus erythematosus. dermatol online j. 2011;17(10):10. published 2011 oct 15. 6. castellino g, govoni m, padovan m, rizzo n, trotta f. beta thalassaemic trait and systemic lupus erythematosus. ann rheum dis. 2005;64(4):653-654. doi:10.1136/ard.2004.023689 7. agrawal bk, marwaha s, bhatnagar m, parry sa, agrawal u. association of systemic lupus erythematosus and beta thalassaemia traita case report. j clin diagn res. 2016;10(6):od03-od4. doi:10.7860/jcdr/2016/19803.7933 8. swamy, m. narayana, t. a. shilpa, and stephen benny. "systemic lupus erythematosus and beta-thalassemia trait." apik journal of internal medicine 8.1 (2020): 22. a. b. mailto:pkamrani@pennstatehealth.psu.edu skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 566 compelling comments the american academy of dermatology camp discovery goes virtual katie a. o’connell, ms1, haya raef, ms2, david x. gao, ba3 1 eastern virginia medical school, norfolk, va 2 tufts university school of medicine, boston, ma 3 university of illinois school of medicine, chicago, il teasing and bullying related to skin disease have been associated with depression, suicidal ideation, and social withdrawal.1 psychological distress can further exacerbate skin conditions, initiating a vicious cycle of stress and disease. specialized summer camps for children with skin disorders have been shown to help enhance quality of life.2 in 1993, the american academy of dermatology (aad) created camp discovery, a one-week residential summer camp experience for children with chronic skin disorders. the entire experience is free of charge and many campers return to camp year after year to be with old friends and make new ones. due to the covid-19 pandemic, camp was transformed into a virtual experience. despite the incredible disappointment over not being able to come together in person, new opportunities emerged for children from different camp locations to meet and expand their networks of support. virtual camp included old traditions such as cabin time, a time where campers would gather in their cabin groups and discuss the day’s activities and play games, and new activities such as slime making, ice-cream making, and virtual family feud. the campers also had the opportunity to attend “gap week” sessions in between the traditional state-specific weeks. this afforded them ongoing fellowship throughout the summer months. not only is camp discovery beneficial for campers, but also volunteers. one study demonstrated that camp volunteerism increases empathy toward children with chronic conditions and provides volunteers with a sense of fulfillment.3 with the abrupt withdrawal of children from their school and social life, activities such as camp discovery may be helpful to restore these important facets of their lives, particularly for children with chronic skin disease. despite the transition to a virtual format, the aad’s camp discovery continued to provide campers with a space to connect and enjoy each other’s company. acknowledgments: the authors thank susan boiko, md for editorial assistance in the preparation of the manuscript. the authors also thank janine mueller, who has coordinated and supported the american academy of dermatology camp discovery for many years. conflict of interest disclosures: none funding: none corresponding author: katie a. o’connell, ms eastern virginia medical school skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 567 phone: 757-310-9601 email: oconnek@evms.edu references: 1. vivar kl, kruse l. the impact of pediatric skin disease on self-esteem. int j womens dermatol. 2018;4(1):27-31. 2. wu j, hogeling m. impact of summer camps for children with chronic skin conditions [published online ahead of print, 2020 aug 3]. j am acad dermatol. 2020;s0190-9622(20)32309-4. 3. bensimon j, wiss k, banker s. impact of camp discovery volunteerism on provider burnout and empathy. j am acad dermatol. 2020;83(2):636638. http://paperpile.com/b/xptstg/tuhat http://paperpile.com/b/xptstg/tuhat http://paperpile.com/b/xptstg/tuhat skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 395 resident competition research articles improvement with fractional ablative laser and topical poly-l-lactic acid in an rdeb patient samantha l. schneider, md,1 marla jahnke, md,1 kristin m. leiferman, md,2 marsha chaffins, md,1 andrew c. krakowski, md,3 and david ozog, md1 1department of dermatology, henry ford hospital, detroit, mi 2department of dermatology, university of utah health care, salt lake city, ut 3division of dermatology, st. luke’s university health network, easton, pa recessive dystrophic epidermolysis bullosa (rdeb) is an autosomal recessively inherited disorder resulting from mutations in col7a1 encoding type vii collagen, a basement membrane zone component. patients with rdeb suffer from skin fragility with limited effective management therapies. fractional ablative laser (fabl) therapy improves scars through collagen remodeling1-4 and has accelerated wound healing in rdeb.5 topical application of poly l-lactic acid (plla) to scars after fabl improved outcomes.6 we report a patient with rdeb with long-standing chronic lesions who experienced clinical and immunohistopathologic improvement with combination fabl-topical plla treatments accompanied by overall patient satisfaction and improvement in quality of life. recessive dystrophic epidermolysis bullosa (rdeb) results from mutations in the col7a1 gene for type vii collagen. affected patients demonstrate skin fragility and blistering with scarring. associated morbidity is great, and there are limited therapeutic options. fractional carbon dioxide (co2) ablative laser (fabl) treatments have been shown to promote collagen remodeling and demonstrate synergy with topical poly-l-lactic acid (plla) applications. we report the case of a young woman with rdeb who experienced decreased blistering, decreased healing time, and improved quality of life in a local skin area treated with fabl followed by topical plla. in comparing biopsy specimens from treated and untreated skin, improved collagen organization and collagen maturity were observed by histopathological examination including with herovici staining. moreover, type vii collagen, absent in untreated skin, was detected in treated affected skin by immunostaining. this report illustrates a treatment response to fabl and topical plla in a patient with rdeb including enhanced healing time, collagen remodeling, and type vii collagen expression. the findings are promising and, with further study, may have broader implications for treating this disorder. abstract introduction skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 396 a young woman with rdeb presented for large non-healing chronic erosions on her upper back and posterior neck (figure 1a) that had been present for years. she had been using topical wound care treatments and oral antibiotics without significant improvement. treatment with an ablative microfractionated 10,600-nm carbon dioxide laser/fabl (ultrapulse encore deep fx; lumenis, ltd., yokneam, israel) was administered to an affected area with single pulse, nonoverlapping stamping technique (15mj energy, 15% density). immediately following fabl, 183.6 g of plla (galderma, fort worth, tx) was applied topically to treated areas. treatments were administered every six weeks on average for a total of fifteen treatments. the patient reported improvement in post-laser healing time, decreased skin fragility, fewer blisters, and overall decreased lesion size (figure 1b) without other changes in her topical regimen. the patient healed in less than one week after six treatments compared to at least two weeks healing time after initial treatments. intraprocedural bleeding markedly decreased as the number of treatments increased. she has had few to no blisters after completion of fifteen treatments and has maintained a decreased overall lesion size over two years. after seven treatments, punch biopsies were obtained from treated affected skin (tas), untreated affected skin (uas), and clinically normal-appearing skin (ns). on hematoxylinand-eosin (h&e) staining, tas demonstrated scar-like fibrosis with chronic dermal inflammation. uas showed detached epidermis overlying abnormal collagen organization with dermal fibrosis and chronic inflammation (figures 2a and 2b). herovici staining, which differentiates mature (type i) from immature (type iii) collagen, revealed an increased expression of type i collagen in tas compared to uas (figures 2c and 2d). tas, uas and ns were evaluated by indirect immunofluorescence for type vii collagen expression. type vii collagen was detected in tas and resembled type vii collagen immunostaining in a normal human control, whereas type vii collagen immunostaining was not detected in uas or ns (figure 3). figure 1. clinical images of the skin preand posttreatments. posterior neck of the patient with recessive dystrophic epidermolysis bullosa (rdeb) reported herein before (figure 1a) and after (figure 1b) fractional ablative laser (fabl) and topical poly-l-lactic acid (plla) treatments (dotted lines indicate treated area). case report a b skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 397 figure 2. histopathology and immunostaining findings on skin biopsy specimens of untreated and treated affected skin and normal-appearing skin. hematoxylin and eosin (h&e) staining of the untreated skin (figure 2a) demonstrates a detached epidermis with dermal fibrosis and chronic inflammation; h&e staining of the treated skin (figure 2b). shows scarring, fibrosis, and chronic dermal inflammation, with an intact epidermis demonstrating compact hyperkeratosis. notably, with respect to collagen organization, the untreated skin demonstrated thick, jumbled collagen (figure 2a), whereas the treated skin had finer collagen bundles with more definite “east-west” organization (figure 2b). herovici staining demonstrates more blue staining of immature type iii collagen in untreated skin (figure 2c) than in treated skin (figure 2d), which demonstrates more pink staining indicating an increase in mature, type i collagen. figure 3. immunofluoresence findings on skin biopsy specimens of untreated affected skin, treated affected skin, and clinically normal skin. indirect immunofluorescence testing for type vii collagen was performed on biopsy specimens from the patient’s untreated affected skin, treated affected skin, clinically normal-appearing/apparently unaffected skin, and normal cadaveric skin (as a positive control) using serum with known igg collagen vii antibodies* as the primary antibody and fluorescein isothiocyanate-conjugated anti-human igg as the secondary/detection antibody. no type vii collagen is detected in the untreated affected skin (figure 3a) or in the clinically normal-appearing skin (figure 3c); however, type vii collagen is detected in treated affected skin (figure 3b) along the basement membrane zone (bmz), white arrowhead, suggesting that fabl and topical plla treatments may induce collagen vii expression. normal cadaver skin (figure 3d) demonstrates the normal bmz collagen vii expression (white arrowhead). *serum from two patients with epidermolysis bullosa acquisita with dermal pattern igg basement membrane zone antibodies on split skin substrate by indirect immunofluorescence and increased igg collagen vii antibody level and normal igg bp 180 and bp 230 antibody levels by elisas showed similar findings. fabl induces collagen remodeling with improved scar texture and cosmesis resulting in improved quality of life due to decreased wound fragility and less visible lesions.1-4 plla acts synergistically with fabl to mediate collagen remodeling.6 three case reports describe the utility of laser therapy in epidermolysis bullosa patients5,7,8; however, this is the first report, of which we are aware, of a patient treated with combination fabltopical plla. fabl likely stimulated healing of the affected area through mechanisms of microdebridement and neocollagenesis.9 heat induced by fabl introduces miniscule channels into the epidermis and superficial discussion skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 398 dermis serving as thermal microdebridement that affects inflammation and, ultimately, collagenesis. plla acts synergistically to induce neocollagenesis. in this model, the response to combination fabl-topical plla is quicker restoration of dermis with less aberrant collagen. this translated to faster healing times and more normal-appearing scar tissue with collagen vii expression on histopathology and immunostaining in the patient reported herein. based on these promising findings, combination fabltopical plla may be a therapeutic option for patients with rdeb who have exhausted conventional therapies. further studies are needed to establish this and to determine, as we theorize, whether this combination therapy may have broader applicability. conflict of interest disclosures: drs. schneider, leiferman, chaffins, krakowski and ozog have no conflicts of interest to disclose. dr. jahnke has a grant funded by the epidermolysis bullosa research partnership and the epidermolysis bullosa medical research foundation. funding: none acknowledgments: we gratefully acknowledge the technicians and technologists in the immunodermatology laboratory at the university of utah for their work in the performance of the indirect immunofluorescence assays reported herein. corresponding author: david ozog, md chairman and clarence s. livingood chair department of dermatology henry ford hospital 3031 w grand boulevard, suite 800 detroit, michigan 48202 tel: (313) 916-4060 fax: (313) 916-5334 email: dozog1@hfhs.org references: 1. ibrahim sm, elsaie ml, kamel mi, mohammed ee. successful treatment of traumatic scars with combined nonablative fractional laser and pinpoint technique of standard co2 laser. dermatol ther. 2016;29(1):52-57. 2. lee sj, suh dh, lee jm, song ky, ryu hj. dermal remodeling of burn scar by fractional co2 laser. aesthetic plast surg. 2016;40(5):761768. 3. ozog dm, liu a, chaffins ml, et al. evaluation of clinical results, histological architecture, and collagen expression following treatment of mature burn scars with a fractional carbon dioxide laser. jama dermatol. 2013;149(1):50-57. 4. tierney e, mahmoud bh, srivastava d, ozog d, kouba dj. treatment of surgical scars with nonablative fractional laser versus pulsed dye laser: a randomized controlled trial. dermatol surg. 2009;35(8):1172-1180. 5. krakowski ac, ghasri p. case report: rapidly healing epidermolysis bullosa wound after ablative fractional resurfacing. pediatrics. 2015;135(1):e207-210. 6. rkein a, ozog d, waibel js. treatment of atrophic scars with fractionated co2 laser facilitating delivery of topically applied poly-l-lactic acid. dermatol surg. 2014;40(6):624-631. 7. hasegawa t, ikeda s. surgical management with co2 laser for pseudosyndactyly in recessive dystrophic epidermolysis bullosa. j dermatol. 2014;41(8):767-768. 8. minicucci em, barraviera sr, miot h, almeidalopes l. low-level laser therapy for the treatment of epidermolysis bullosa: a case report. j cosmet laser ther. 2010;12(4):203-205. 9. krakowski ac, ozog dm, ginsberg d, cheng c, chaffins ml. laser-induced neocollagenesis in focal dermal hypoplasia associated with goltz syndrome in a girl. jama dermatol. 2017;153(12):1292-1297. mailto:dozog1@hfhs.org skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 152 brief articles dysmorphic trichophyton rubrum mimicking blastomycosis landon hope mba1, sidra ibad ba2, etan marks do3, richard hope md4, clay j. cockerell md3 1texas tech university health sciences center lubbock, tx 2icahn school of medicine at mount sinai, new york, ny 3university of texas medical center/ cockerell dermatopathology dallas, tx 4lubbokc dermatology and skin cancer center, lubbock, tx trichophyton rubrum is the most common fungal organism causing cutaneous dermatophyte infections worldwide. traditionally, infections are limited to the epidermal layer of the skin causing common dermatophytosis. t. rubrum has been reported to be an invasive organism in immunocompromised hosts.1 blastomycosis is a deep fungal infection that is more prevalent in immunocompromised hosts than t. rubrum. it is typically a soil organism that may be inhaled leading to systemic disease with skin manifestations.2 immunosuppression required for transplant patients puts them at an increased risk for severe systemic infections from otherwise non or minimally pathogenic organisms. a 60 year old male patient with a history of a renal cell carcinoma, renal transplant, diabetes and hypertension presented with several erythematous papules, plaques and nodules on his right calf, his upper left chest, and along the arch of his right foot. the patient’s medications included tacrolimus (0.5 mg), prednisone (10mg), nifedipine (90mg), metoprolol (100mg), simvastatin (10mg), sulfamethoxazole/trimethoprim, insulin (100units/ml), furosemide (20mg), mycophenolic acid (360 mg), valganciclovir (450mg), cinacalcet (60mg), and glipizide (5mg) for control of the respective conditions. the patient was diagnosed and treated for renal cell carcinoma 4 years prior to his transplant. he had the renal transplant 6 months prior to the dermatology consultation. introduction we describe a 62 year old immunocompromised, diabetic, male patient who presented with well-defined erythematous plaques on his right calf, a papule on his upper left chest, and several nodules along the arch of his right foot. the patient was 4 years post-nephrectomy due to renal cell carcinoma and 6 months post-renal transplantation at the time of presentation. initial clinical impression was thought to be deep fungal infection or metastatic carcinoma. trichophyton rubrum with a dysmorphic morphology simulating blastomycosis was ultimately diagnosed. abstract case report skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 153 the nodules and plaques appeared soon after transplant and then began enlarging which prompted a dermatology referral. examination showed a well-defined erythematous papule on the upper left chest (figure 1). scaly plaques were observed on the right calf and several erythematous firm nodules were noted on the right arch and ankle (figure 2). additionally, onychomycosis was observed on both great toenails. biopsies for histopathology and cultures were obtained from the right ankle and left chest. the initial impression of the clinician was a deep fungal infection versus metastatic cancer. biopsy specimens using hematoxylin and eosin stains showed suppurative granulomatous dermatitis, pseudocarcinomatous hyperplasia, multinucleated histiocytes and what appeared to be broad-based budding yeast. a periodic acid-schiff stain highlighted and confirmed numerous spores in the dermis, many of which were broad based budding yeast-like organisms. a fite stain was negative for microorganisms. these findings were consistent with blastomycoses due to the morphology of the organisms; therefore, the patient was started on itraconazole 200 mg to be taken twice daily for thirteen months. additional tests were done to monitor liver function including monthly aspartate aminotransferase (ast) and alanine aminotransferase (alt) for the first 3-4 months and then every other month thereafter. at four weeks, the cultures had failed to grow bacteria, mycobacteria or deep fungal organisms. specifically, blastomycosis spp. did not grow, but t. rubrum was identified. this unexpected result was communicated with the dermatopathologist who subsequently suspected t. rubrum with a dysmorphic morphology simulating blastomycosis. the specimens were sent to the centers for disease control, and they failed to identify blastomycosis dna. diagnosis of dysmorphic trichophyton rubrum was confirmed with positive cultures and when a dna probe failed to identify blastomycoses markers. the patient continued to show clinical response to itraconazole, and after 13 months repeat biopsies of the resolving lesions showed only hypertrophic scar tissue with a negative periodic acid-schiff stain. there was no evidence of the t. rubrum cutaneous infection. both great toenails had been cleared of onychomycosis. three months after cessation of treatment (at the time of this report) there has been no recurrence of infection. figure 1. erythematous papules on the chest. skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 154 figure 2. erythematous papules on right ankle & foot. figure 3-5. suppurative granulomatous dermatitis with pseudoepitheliomatous hyperplasia, and broadbased budding yeast. figure 4. figure 5. figure 6. a pas stain is positive. t. rubrum commonly causes onychomycosis, tinea pedis, tinea cruis, tinea corporis, and tinea capitis.3 additionally, it is more common in immunocompromised patients. rarely, as in the case presented, it can become an invasive organism. in cases of invasive t. rubrum, onychomycosis is commonly observed. terbinafine is the preferred treatment of t. rubrum.4 however, our patient was having a clinical response to itraconazole 200mg twice daily and was discussion skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 155 tolerating it well. therefore, this therapeutic regiment was continued until final biopsies showed total resolution of the infection. the findings of the periodic acid-schiff and fite stains were consistent with blastomycoses; however, cultures and dna probes showed the growth of t. rubrum and the absence of blastomycoses. both blastomycosis and t. rubrum are characterized by increased risk in immunocompromised/immunosuppressed individuals and granulomatous nodule presentations. this presents a unique challenge for dermatopathologists because the dysmorphic morphology of t. rubrum resembles that of blastomycoses, yielding incorrect initial diagnoses if no further tests are conducted. incorrect initial diagnoses lead to the prescription of medications that are less than ideal in treating the underlying disease. additional tests would include immunostaining using anti-mycobacterium and anti-trichophyton antibodies, pcr confirmation, and testing on sabouraud dextrose agar. especially because t. rubrum is not particularly invasive, the initial diagnosis is usually not questioned. conflict of interest disclosures: none funding: none corresponding author: etan marks, do phone:847-951-8359 e-mail: cjcconsults@gmail.com references: 1. wolfson js, sober aj, rubin rh. dermatologic manifestations of infections in immunocompromised patients. medicine 1985;64:115-31. 2. kwon-chung, k. j. (k. june) and bennett, john e. (john eugene), 1933medical mycology. lea & febiger, philadelphia, 1992. 3. venkatesan, p. , perfect, j. r. and myers, s. a. evaluation and management of fungal infections in immunocompromised patients. dermatologic therapy 2005;18: 44-57. 4. zaias n, serrano l. the successful treatment of finger trichophyton rubromonychomycosis with oral terbafine. clinical and experimental dermatology;1989; 14: 120-123 mailto:cjcconsults@gmail.com powerpoint presentation objective rapid and sustained improvements in itch and sleep with tralokinumab treatment in patients with moderate-to-severe atopic dermatitis, a post hoc analysis of pooled data from ecztra 1 and 2 eric simpson1, andreas wollenberg2, weily soong3, thomas mark4, alexandra kuznetsova4, louise abildgaard steffensen4, jonathan i silverberg5 • atopic dermatitis (ad) is a chronic skin disease associated with significant itch and sleep disturbances that profoundly affect patients’ daily lives • tralokinumab is a fully human, high-affinity, monoclonal antibody that specifically neutralizes the interleukin-13 cytokine, a key driver of ad signs and symptoms • in two pivotal phase 3 trials (ecztra 1, nct03131648; ecztra 2, nct03160885) in adults with moderate-to-severe ad, tralokinumab monotherapy demonstrated superiority compared to placebo for each primary and secondary endpoint at week 16 and was well tolerated up to 52 weeks of treatment1 trial design to evaluate the timing and effect of tralokinumab on itch and sleep in adult patients with moderate-to-severe ad pooled from two identical phase 3 trials. 1department of dermatology, oregon health & science university, portland, or, usa; 2department of dermatology and allergy, university hospital, ludwig maximilian university of munich, munich, germany; 3alabama allergy & asthma center and clinical research center of alabama, birmingham, al, united states; 4leo pharma a/s, ballerup, denmark; 5george washington university school of medicine and health sciences, washington, dc introduction methods • ecztra 1 and 2 were two identically designed, multinational, double-blind, randomized, placebo-controlled, 52-week trials (figure 1) • patients were randomized 3:1 to subcutaneous tralokinumab 300 mg or placebo every 2 weeks for an initial 16 weeks • prior to randomization, ad treatments were washed out: 4 weeks for systemic treatments and 2 weeks for tcs and other topical treatments • rescue treatment could be used at the discretion of the investigator to control intolerable symptoms figure 1. ecztra 1 and 2 trial design. table 1. baseline demographics and clinical characteristics. patients, demographics, and clinical characteristics references disclosures conclusions tralokinumab monotherapy showed rapid and sustained improvements from baseline in itch and sleep interference relative to placebo, starting from day 2 after the first dose. 1.. wollenberg a et al. br j dermatol. 2020 sep 30. doi: 10.1111/bjd.19574. online ahead of print. eric simpson is a consultant and investigator for regeneron/sanofi, dermira, menlo pharmaceuticals, lilly, abbvie, genentech, medimmune, gsk, leo pharma, celgene, and pfizer. andreas wollenberg has received grants, personal fees, or nonfinancial support from abbvie, almirall, beiersdorf, bioderma, chugai, galapagos, galderma, hans karrer, leo pharma, lilly, l’oreal, maruho, medimmune, novartis, pfizer, pierre fabre, regeneron, santen, and sanofi-aventis. weily soong has served on the advisory board and received research grants from genentech, inc., teva, novartis, and pfizer; served on the advisory board, received research grants, and was a speaker for astrazeneca, regeneron, sanofi, and glaxosmithkline; received research grants and was a speaker for optinose; received research grants from avillion, gossamer bio, 3m, and leo pharma. thomas mark, alexandra kuznetsova, and louise abildgaard steffensen are employees of leo pharma a/s. jonathan i. silverberg reports honoraria as a consultant/advisory board member from leo pharma and has acted as a consultant for, and/or received grants/honoraria from, abbvie, anaptysbio, asana biosciences, galderma research and development, glaxosmithkline, glenmark, kiniksa, leo pharma, lilly, medimmune, menlo therapeutics, pfizer, puricore, regeneron, and sanofi. acknowledgements • the ecztra 1 and 2 clinical trials were sponsored by leo pharma a/s • editorial support was provided by clair geary, phd of alphabet health (new york, ny), supported by leo pharma a/s, according to good publication practice guidelines (https://www.ismpp.org/gpp3). figure 2. percent improvement from baseline in weekly average over 16 weeks in: a. worst daily pruritus nrs b. eczema related sleep nrs results all randomized (n=1596) tralokinumab q2w (n=1196) placebo (n=400) mean age in years (sd) 37.8 (14.4) 37.9 (14.2) 37.2 (14.8) male, n (%) 947 (59.3) 710 (59.4) 237 (59.3) region, n (%) north america 559 (35.0) 419 (35.0) 140 (35.0) europe 711 (44.5) 533 (44.6) 178 (44.5) australia 121 (7.6) 90 (7.5) 31 (7.8) asia 205 (12.8) 154 (12.9) 51 (12.8) mean affected bsa, % 52.9 (24.9), n=1595 52.7 (24.8) 53.6 (25.3), n=399 mean disease duration, years (sd) 28.2 (15.2), n=1594 28.1 (15.2), n=1195 28.5 (14.9), n=399 severe disease (iga 4), n (%) 794 (49.7) 591 (49.4) 203 (50.8) mean easi (sd) 32.3 (14.0), n=1590 32.2 (14.0), n=1192 32.7 (13.9), n=398 mean total scorad (sd) 70.4 (13.0), n=1590 70.2 (13.2), n=1192 71.1 (12.4), n=398 mean dlqi (sd) 17.3 (7.1), n=1572 17.2 (7.1), n=1178 17.5 (7.0), n=394 mean weekly average worst daily pruritus nrs (sd) 7.8 (1.4), n=1577 7.8 (1.4), n=1182 7.8 (1.4), n=395 mean weekly average eczema related sleep nrs (sd) 7.0 (2.0), n=1577 7.0 (2.0), n=1182 7.0 (2.0), n=395 • at week 16, tralokinumab had a greater adjusted mean percentage improvement from baseline in weekly average of worst daily pruritus nrs (tralokinumab 35.5%, placebo 21.4%; p<0.001) and eczema-related sleep interference (tralokinumab 39.7%, placebo 18.4%; p<0.001) compared to placebo (figure 2) effect on itch and sleep over 16 weeks figure 3. percent improvement from baseline by day in: a. worst daily pruritus nrs b. eczema related sleep nrs • relative to the placebo group, a significantly greater proportion of patients in the tralokinumab group achieved ≥2 or ≥4 point improvement after:† o 3 days for worst daily pruritus nrs ≥2 (at day 3, tralokinumab: 29.7%, placebo: 20.0%; difference [95% ci]: 11.9 % [7.4%, 16.4%]; p<0.001) o 4 days for worst daily pruritus nrs ≥4 (at day 4, tralokinumab: 10.1%, placebo: 7.5%; difference: 3.7 % [1.5%, 6.0%]; p=0.008) o 2 days for eczema related sleep nrs ≥2 (day 2, tralokinumab: 29.7%, placebo: 24.0%; difference: 6.2 % [1.3%, 11.2%]; p=0.018) o 3 days for eczema related sleep nrs ≥4 (at day 3, tralokinumab: 11.0%, placebo: 8.2%; difference: 4.3 % [1.8%, 6.8%]; p=0.005) ecztra 1 & 2: phase 3, randomized, double-blind, placebo-controlled trials ad, atopic dermatitis; easi, eczema area and severity index; iga, investigator’s global assessment; q2w, every 2 weeks; q4w, every 4 weeks; tcs, topical corticosteroid. wollenberg a et al. br j dermatol 2020. 16 weeks0–6 weeks 52 weeks 66 weeks tralokinumab 300 mg q2w placebo q2w tralokinumab 300 mg q2w tralokinumab 300 mg q4w placebo q2w placebo q2w tralokinumab 300 mg q2w optional tcs and optional home use initial treatmentscreening maintenance treatment patients with clinical response iga-0 / 1 or easi-75 safety follow-up ecztra 1 (n=603) and 2 (n=593) ecztra 1 (n=199) and 2 (n=201) 3:1 randomization patients not achieving iga=0/1 or easi 75 at 16 weeks up to 6 weeks washout of ad medication (2 weeks for tcs) 300 mg q2w after initial loading dose (600 mg) 2:2:1 randomization patients with clinical response criteria iga 0/1 or easi-75 patients not achieving iga 0/1 or easi-75 at 16 weeks open-label tralokinumab 300 mg q2w + optional tcs (n=686) key eligibility criteria • ≥18 years of age • confirmed diagnosis of atopic dermatitis for ≥1 year • easi score ≥12 at screening and ≥16 at baseline • iga score ≥3 • ad involvement of ≥10% body surface area • worst daily pruritus numeric rating scale (nrs) average score ≥4 during week prior to baseline • candidates for systemic therapy due to a recent (within 1 year) history of inadequate response or intolerance to topical treatment outcomes • easi and iga were assessed at baseline and at scheduled biweekly visits throughout the trials • itch and sleep interference were recorded daily by patients using: o numeric rating scale (nrs) for worst daily pruritus (11-point scale with 0 being “no itch” and 10 being “worst itch imaginable”) o nrs for eczema-related sleep interference (11-point scale with 0 indicating that it “did not interfere” and 10 indicating that it “completely interfered”) analyses • this post hoc analysis was conducted of pooled data from ecztra 1 and ecztra 2 trials through week 16 • statistical analyses followed pre-specifications: o difference in iga 0/1 and easi-75 response rates were assessed at week 16 in a pre-specified pooled analysis of the primary endpoints using the cochranmantel-haenszel stratified by region, baseline investigator’s global assessment (iga) and trial. missing data or data after rescue medication (including tcs) were imputed as non-response o change from baseline in worst daily pruritus, eczema-related sleep interference were assessed both as weekly averages of worst daily measures (baseline to week 16) as well as the single worst daily measures (baseline to day 6) in post-hoc analyses using a mixed model for repeated measures with fixed effects of planned treatment, region, baseline iga, trial and interactions between treatment and visit and baseline value and visit. data collected after permanent discontinuation or initiation of rescue medication (including tcs) were set to missing o difference in worst daily pruritus and eczema-related sleep interference response rates (nrs ≥2 and nrs≥4) were assessed using the single worst daily measures (baseline to day 12) in post-hoc analyses using the cochranmantel-haenszel stratified by region, baseline investigator’s global assessment (iga), and trial. missing data or data after rescue medication (including tcs) were imputed as non-response o p values are nominal without multiplicity adjustment • 802 and 794 patients were randomized in ecztra 1 and 2, respectively (tralokinumab, n=1196; placebo, n=400) • baseline demographics and clinical characteristics were well balanced between treatment groups (table 1) iga 0/1 and easi-75 at week 16 • significantly more patients achieved the primary endpoints of iga 0/1 (tralokinumab 19.0%, placebo 9.0%; p<0.001) and a 75% reduction in eczema area and severity index (easi-75; tralokinumab 29.0%, placebo 12.1%; p<0.001) at week 16 with tralokinumab versus placebo† 0 2 4 6 8 10 12 14 16 0 10 20 30 40 % improvement in worst daily prurit us nrs from baseline (weekly average) weeks post baseline % im p ro ve m en t ov er t im e *** *** *** *** *** *** *** *** *** *** *** *** ****** ****** 2 4 6 8 10 12 14 16 10 0 10 20 30 40 50 % improvement in eczema relat ed sleep nrs from baseline (weekly average) weeks post baseline % im p ro ve m en t ov er t im e tralokinumab placebo *** *** *** *** *** *** *** *** *** *** *** *** *** *** *** *** • a greater improvement from baseline was seen in worst daily pruritus nrs from day 2 (p=0.001), and in eczema-related sleep interference from day 1 (p<0.05) with tralokinumab compared to placebo (figure 3) timing of the effect on itch and sleep 0 1 2 3 4 5 6 0 5 10 15 % improvement in worst daily prurit us nrs from baseline (by day) days post baseline % im pr ov em en t o ve r t im e ** *** *** *** *** 1 2 3 4 5 6 5 0 5 10 15 % improvement in eczema relat ed sleep nrs from baseline (by day) days post baseline% im pr ov em en t o ve r t im e tralokinumab placebo * *** *** *** *** *** data shown are adjusted mean percentage change ±se from repeated measurements model. data collected after permanent discontinuation or initiation of rescue medication (including tcs) were set to missing. *p<0.05; **p<0.01; ***p<0.001. data shown are adjusted mean percentage change ±se from repeated measurements model. data collected after permanent discontinuation or initiation of rescue medication (including tcs) were set to missing. *p<0.05; **p<0.01; ***p<0.001. †missing data or data after collected after rescue medication (including tcs) were imputed as non-response. a b a b rapid and sustained improvements in itch and sleep with tralokinumab treatment in patients with moderate-to-severe atopic dermatitis, a post hoc analysis of pooled data from ecztra 1 and 2 powerpoint presentation topical tirbanibulin eradication of periungual squamous cell carcinoma angela yen moore,1,2 stephen moore,1,3,4 qin he,3 peter rady,3 ayman grada,5 stephen tyring3 1arlington research center, arlington, tx, usa; 2baylor university medical center, dallas, tx, usa; 3department of dermatology, the university of texas mcgovern medical school, houston, tx, usa; 4 rice university, houston, tx, usa; 5grada dermatology research llc, chesterbrook, pa, usa introduction • actinic keratosis (ak) are precancerous lesions that if left untreated may lead to invasive squamous cell carcinoma (scc) 1 (fernandez) • tirbanibulin (kx2-391, kx01) is a synthetic, highly selective, novel inhibitor of tubulin polymerization and src kinase signaling developed as a first-in-class topical formulation for the treatment for ak 2 (smolinksi) • previous phase i and ii studies demonstrated that tirbanibulin ointment 1% was active against ak lesions on the forearm and face or scalp, respectively. local skin reactions (lsrs) were mostly transient and mild-to-moderate in severity, and tirbanibulin was well tolerated 3 (dubois phase i and phase ii) • tirbanibulin ointment 1% once-daily for 5 days resulted in higher overall complete ak clearance rates at day 57 than vehicle in two phase iii studies (kx01-ak-003: 44% vs 5%; kx01-ak-04: 54% vs 13%, respectively; p<0.0001) 4 (blauvelt) figure 2: ncbi-blast alignment of sequencing data obtained from the hpv-pcr product the sequence data obtained from patient’s sample (query) showed 95% identities to the prototype hpv 57 dna deposited into the ncbi genebank (sbjct). • 29-year-old non-smoking male had a biopsyconfirmed squamous cell carcinoma in situ at the distal periungual tip of the left fourth fingernail 5 • previous treatment with imiquimod and monthly liquid nitrogen for 6 months had failed. • tirbanibulin 1% ointment was applied for 5 days with complete resolution on the fifth day without reported erythema, edema, or irritation figure 1a: firm verrucous plaque at distal periungual tip of the left 4th digit before treatment with tirbanibulin 1% ointment figure 1b: complete resolution of squamous cell carcinoma after 5 days of topical tirbanibulin 1% ointment figure 1a figure 1b discussion case report results conclusion references results • hpv typing by nested pcr was performed on paraffin-embedded block methods • hpv 57 was detected (figure 2), • further research on the mechanism of tirbanibulin effect on hpv as well as scc are required to confirm these findings. • although hpv 57 is most commonly associated with common warts, hpv 57 has also been reported with oral papillomas, esophageal scc, and cutaneous scc. • even though it is fda-approved in the u.s. for treatment of actinic keratosis, tirbanibulin ointment may have efficacy on scc or directly on hpv-driven carcinogenesis. 1. fernandez figueras mt. from actinic keratosis to squamous cell carcinoma: pathophysiology revisited. j eur acad dermatol venereol. 2017;31 suppl 2:5-7. doi:10.1111/jdv.14151 2. smolinski mp, bu y, clements j, et al. discovery of novel dual mechanism of action src signaling and tubulin polymerization inhibitors (kx2-391 and kx2361). j med chem. 2018;61(11):4704-4719. doi:10.1021/acs.jmedchem.8b00164 3. smolinski mp, bu y, clements j, et al. discovery of novel dual mechanism of action src signaling and tubulin polymerization inhibitors (kx2-391 and kx2361). j med chem. 2018;61(11):4704-4719. doi:10.1021/acs.jmedchem.8b00164 4. blauvelt a, kempers s, forman s, lain e, bruce s. tirbanibulin ointment 1%, a novel inhibitor of tubulin polymerization and src kinase signaling , for the treatment of actinic keratosis (ak): results from two pivotal phase iii studies. j of skin. 2020;4(5):s63-s63. doi:10.25251/skin.4.supp.62 5. moore ay, moore s. topical tirbanibulin eradication of periungual squamous cell carcinoma. jaad case reports. 2021;14:101-103. doi:10.1016/j.jdcr.2021.06.013 https://doi.org/10.1111/jdv.14151 https://doi.org/10.1021/acs.jmedchem.8b00164 https://doi.org/10.1021/acs.jmedchem.8b00164 https://doi.org/10.25251/skin.4.supp.62 https://doi.org/10.1016/j.jdcr.2021.06.013 skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 44 research letter disparities in overall survival in patients with melanoma by race/ethnicity, socioeconomic status, and healthcare systems amanda rosenthal, md1, shivani reddy, md2, joanie chung, mph3, christina kim, md1, robert cooper, md4, reina haque, phd3,5 1 department of dermatology, kaiser permanente los angeles medical center, los angeles, ca 2 california skin institute, mountain view, ca 3 department of research & evaluation, kaiser permanente southern california; kaiser permanente los angeles medical center, los angeles, ca 4 department of pediatric hematology/oncology, southern california permanente medical group, kaiser permanente los angeles medical center, los angeles, ca 5 department of health systems science, kaiser permanente bernard j. tyson school of medicine, los angeles, ca insurance status, a proxy for access to care, is an established correlate of cancer outcomes. prior work in the field of healthcare disparities among melanoma patients, however, has included a mix of patients both with and without health insurance, making it difficult to disentangle the effects of various other sociodemographic factors.1-5 in order to mitigate disparities and improve outcomes, we sought to independently examine the effects of these intertwined sociodemographic variables on all-cause mortality within an insured population of melanoma patients. further, we aimed to evaluate the effects of health insurance coverage type, that is, whether patients were cared for within an integrated healthcare system or within a traditional model of healthcare, on all-cause mortality risk. our objective was to quantify the effect of race/ethnicity, socioeconomic status (ses) and healthcare system on overall mortality within an insured population of patients diagnosed with melanoma in southern california from 2009 to 2014, and followed through 2017. healthcare system was classified as those within kaiser permanente southern california’s (kpsc) network, a vertically integrated healthcare system, and insured patients outside of kpsc’s network with other private insurance (opi). using a retrospective cohort study design with data from the california cancer registry, we identified 14,614 adults diagnosed with melanoma (stage 0-iv). the dataset included ses information based on geocoded data. the total number of deaths was 2,456 (16.8%) over a maximum follow up of 8 years. we examined person-year (py) mortality rates and conducted cox proportional hazard models, adjusted for age, sex, year of diagnosis, stage at diagnosis, race/ethnicity, ses, county of residence, and primary and adjuvant therapy. skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 45 table 1. demographic characteristics of patients diagnosed with melanoma between 2009-2014 in southern california by health care system kpsc opi overall n (%) n (%) n (%) total 4701 (100%) 9913 (100%) 14614 (100%) age at time of melanoma diagnosis 20-39 years 461 (9.8%) 1033 (10.4%) 1494 (10.2%) 40-64 years 2235 (47.5%) 4711 (47.5%) 6946 (47.5%) 65+ years 2005 (42.7%) 4169 (42.1%) 6174 (42.2%) sex female 1942 (41.3%) 4061 (41%) 6003 (41.1%) male 2759 (58.7%) 5850 (59%) 8609 (58.9%) socioeconomic status (ses) lowest ses 361 (7.7%) 510 (5.1%) 871 (6%) lower-middle ses 662 (14.1%) 1077 (10.9%) 1739 (11.9%) middle ses 1033 (22%) 1736 (17.5%) 2769 (18.9%) upper-middle ses 1389 (29.5%) 2556 (25.8%) 3945 (27%) highest ses 1256 (26.7%) 4034 (40.7%) 5290 (36.2%) race/ethnicity non-hispanic white 3904 (83%) 8721 (88%) 12625 (86.4%) hispanic 521 (11.1%) 629 (6.3%) 1150 (7.9%) non-hispanic black 134 (2.9%) 89 (0.9%) 223 (1.5%) asian/pacific islander 80 (1.7%) 142 (1.4%) 222 (1.5%) american indian 10 (0.2%) 17 (0.2%) 27 (0.2%) other/unknown 52 (1.1%) 315 (3.2%) 367 (2.5%) county of residence imperial 1 (0%) 27 (0.3%) 28 (0.2%) los angeles 1848 (39.3%) 3573 (36%) 5421 (37.1%) orange 764 (16.3%) 2481 (25%) 3245 (22.2%) riverside 546 (11.6%) 1080 (10.9%) 1626 (11.1%) san bernardino 386 (8.2%) 715 (7.2%) 1101 (7.5%) san diego 1156 (24.6%) 2037 (20.5%) 3193 (21.8%) stage at diagnosis i 3311 (70.4%) 6123 (61.8%) 9434 (64.5%) ii 529 (11.2%) 1383 (13.9%) 1912 (13.1%) iii 255 (5.4%) 837 (8.4%) 1092 (7.5%%) iv 164 (3.5%) 432 (4.4%) 596 (4.1%) unknown 442 (9.4%) 1138 (11.5%) 1580 (10.8%) kpsc, kaiser permanente southern california; opi, other private insurance. skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 46 table 2. overall mortality rates per 1000 person-years and overall mortality per multivariate adjusted hazard ratios by health care system stratified by age at time of melanoma diagnosis, and race/ethnicity,* ses, and stage of melanoma kpsc opi total # deaths rate per 1000 py (95% ci) hr (95% ci) # deaths rate per 1000 py (95% ci) hr (95% ci) # deaths rate per 1000 py (95% ci) hr (95% ci) total 729 45.9 (42.7,49.4) n/a 1727 53.6 (51.1,56.1) n/a 2456 51.0 (49,53.1) n/a age at time of melanoma diagnosis 20-39 years 17 10.1 (5.9,16.1) 1 (ref) 55 15 (11.3,19.5) 1 (ref) 72 13.4 (10.5,16.9) 1 (ref) 40-64 years 157 19.8 (16.8,23.2) 1.75 (1.06,2.90) 386 24.4 (22,26.9) 1.61 (1.21,2.14) 543 22.8 (21,24.9) 1.63 (1.28,2.09) 65+ years 555 88.6 (81.4,96.3) 7.65 (4.67,12.51) 1286 101.1 (95.6,106.8) 6.21 (4.68,8.25) 1841 97.0 (92.6,101.5) 6.65 (5.21,8.49) race/ethnicit y non-hispanic white 626 46.9 (43.3,50.7) 1 (ref) 1558 54.6 (51.9,57.3) 1 (ref) 2184 52.1 (50,54.4) 1 (ref) hispanic 64 38.2 (29.4,48.8) 0.72 (0.54,0.95) 114 63.3 (52.2,76.1) 0.79 (0.64,0.96) 178 51.2 (44,59.3) 0.76 (0.65,0.9) non-hispanic black 25 62.1 (40.2,91.7) 0.87 (0.57,1.32) 19 66.3 (39.9,103.6) 1.00 (0.63,1.60) 44 63.9 (46.4,85.7) 0.92 (0.68,1.26) asian/pacific islander 13 56.1 (29.9,95.9) 0.95 (0.54,1.66) 29 71.4 (47.8,102.5) 1.24 (0.85,1.80) 42 65.8 (47.4,89) 1.12 (0.82,1.53) american indian 1 29.5 (0.7,164.3) 0.57 (0.08,4.08) 3 68.2 (14.1,199.4) 1.73 (0.43,6.94) 4 51.4 (14,131.5) 1.06 (0.34,3.29) other/unkno wn 4 3.5 (0.9,8.8) 0.09 (0.03,0.25) 4 3.0 (0.8,7.7) 0.083 (0.03,0.22) socioecono mic status (ses) lowest ses 69 57.7 (44.9,73.1) 1.47 (1.09,2.00) 137 96.4 (80.9,113.9) 1.80 (1.47,2.22) 206 78.7 (68.3,90.2) 1.70 (1.43,2.02) lower-middle ses 103 47.5 (38.8,57.6) 1.40 (1.08,1.80) 264 77 (68,86.9) 1.50 (1.28,1.76) 367 65.6 (59,72.6) 1.47 (1.29,1.68) middle ses 164 46.5 (39.7,54.2) 1.28 (1.03,1.60) 348 64 (57.4,71.1) 1.39 (1.21,1.61) 512 57.1 (52.3,62.3) 1.36 (1.21,1.53) upper-middle ses 210 44.3 (38.5,50.7) 1.15 (0.94,1.41) 422 50.1 (45.4,55.1) 1.19 (1.04,1.35) 632 48.0 (44.3,51.9) 1.19 (1.07,1.33) highest ses 183 43.1 (37.1,49.8) 1 (ref) 556 41.1 (37.8,44.7) 1 (ref) 739 41.6 (38.6,44.7) 1 (ref) stage at diagnosis i 293 24.8 (22.0,27.8) 1 (ref) 484 22.8 (20.8,25.0) 1 (ref) 777 23.5 (21.9,25.2) 1 (ref) ii 142 88.6 (74.6,104.4) 2.58 (2.10,3.16) 398 22.8 (20.8,25.0) 2.98 (2.60,3.41) 540 91.5 (83.9,99.5) 2.85 (2.55,3.19) iii 87 117.8 (94.3,145.3) 4.55 (3.54,5.84) 300 125.9 (112.0,140.9) 4.40 (3.79,5.11) 387 124.0 (111.9,136.9) 4.38 (3.86,4.97) iv 114 460.7 (380.0,553. 5) 13.34 (10.01,17.79) 320 507.9 (453.7,566.7) 10.54 (8.79,12.64) 434 494.6 (449.1,543.4) 11.28 (9.70,13.11) unknown 93 64.0 (51.7,78.4) 2.01 (1.57,2.56) 225 60.2 (52.6,68.6) 2.08 (1.77,2.45) 318 61.3 (54.7,68.4) 2.04 (1.79,2.34) kpsc, kaiser permanente southern california; opi, other private insurance. * insufficient power to determine statistical sign ificance among asian/pacific islanders and american indians skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 47 table 1 shows the distribution of demographics of the insured patients by healthcare system. kpsc had more minorities and those in the lowest two ses quintiles. table 2 provides the py all-cause mortality rates and multivariate adjusted hazard ratios (hr) by healthcare system. py mortality rates by race/ethnicity did not yield significant results, possibly given the small numbers of deaths in certain populations. mortality rates increased by decreasing ses quintile in the overall population. when stratifying by healthcare system, the py mortality rates among those patients in kpsc were much more similar among ses groups, with the 95% confidence intervals (ci) overlapping for all five ses quintiles. by contrast, in opi, the cis for the lowest, lowermiddle, and middle ses groups did not overlap with the cis of the upper-middle and highest ses groups. of note, the kpsc patients in the three lowest ses quintiles had statistically significant decreased mortality rates compared to their opi counterparts. in multivariable adjusted hazard models, we did not observe differences in mortality risk by race/ethnicity in either healthcare system, when using non-hispanic whites as the reference population. we did appreciate an increased mortality risk by decreasing ses quintile in kpsc and opi, when using the highest ses quintile as the reference population. this trend, however, was much more apparent in the opi group. for example, the poorest patients in opi had a mortality risk 80% greater than wealthiest patients in opi (hr 1.80; 95% ci 1.47, 2.22), while the poorest patients in kpsc had a 47% greater risk than the wealthiest patients in kpsc (hr 1.47; 95% ci 1.09, 2.00). in summary, our results suggest that disparities in overall mortality persist, even in a cohort with health insurance coverage, and that lower ses is an important driver of this disparity. we also underscore the survival advantages for those vulnerable populations cared for within an integrated healthcare network, such as kpsc. conflict of interest disclosures: none funding: this study was funded by kaiser permanente southern california’s regional research committee. corresponding author: amanda rosenthal, md department of dermatology kaiser permanente los angeles medical center 1515 n vermont ave los angeles, ca 90027 amanda.x.rosenthal@kp.org references: 1. dawes sm, tsai s, gittleman h, barnholtz-sloan js, bordeaux js. racial disparities in melanoma survival. journal of the american academy of dermatology. 2016;75(5):983-91. 2. collins kk, fields rc, baptiste d, liu y, moley j, jeffe db. racial differences in survival after surgical treatment for melanoma. annals of surgical oncology. 2011;18(10):2925-36. 3. wu x-c, eide mj, king j, saraiya m, huang y, wiggins c, et al. racial and ethnic variations in incidence and survival of cutaneous melanoma in the united states, 1999-2006. journal of the american academy of dermatology. 2011;65(5):s26. e1-s. e13. 4. zell ja, cinar p, mobasher m, ziogas a, meyskens jr fl, anton-culver h. survival for patients with invasive cutaneous melanoma among ethnic groups: the effects of socioeconomic status and treatment. journal of clinical oncology: official journal of the american society of clinical oncology. 2008;26(1):66-675. 5. cormier jn, xing y, ding m, lee je, mansfield pf, gershenwald je, et al. ethnic differences among patients with cutaneous melanoma. archives of internal medicine. 2006;166(17):190714. mailto:amanda.x.rosenthal@kp.org microsoft word systemic ad.doc skin copyright 2017 the national society for cutaneous medicine 8 in-depth reviews systemic manifestations of atopic dermatitis: a systematic review l. bonomoa, a.j. ramos-rodriguez, mdb, and e. guttman-yassky, md, phda,c aicahn school of medicine at mount sinai, department of dermatology, new york, ny bicahn school of medicine at mount sinai, department of medicine, new york, ny claboratory for investigative dermatology, the rockefeller university, new york, ny a atopic dermatitis (ad) is known to be associated with other allergic diseases. these conditions include asthma, food allergy, and allergic rhinoconjunctivitis1. ad typically occurs in early childhood with allergic comorbidities developing later in life in a serial fashion. this progression is termed the “atopic march” and is july 2017 volume i issue i background: atopic dermatitis (ad) is known to be associated with other allergic diseases, which often develop later in life in a serial fashion. this progression is termed the “atopic march” and is considered the classical presentation of atopic disease. however, recent evidence suggests that this paradigm may not hold true for a significant portion of patients with these conditions. not only is the timing of development likely more complex than previously believed, the comorbidities associated with ad are possibly more numerous and varied. methods: this two-step systematic review involved a targeted search of pubmed and embase with an additional hand search of key journals. the terms “atopic dermatitis” and “atopic eczema” were searched in conjunction with multiple keywords representing the concept of systemic nature of disease. all titles and abstracts were subsequently screened for relevance to the research question. results: this review’s evidence supports an association between ad and other atopic diseases. however, it also suggests that the classical paradigm of the “atopic march” does not apply to all patients with atopic dermatitis. there appears to be a significant association between ad and multiple neuro-psychiatric comorbidities, particularly asd and adhd. additional themes supported by lower-level evidence are increased risk of cardiovascular disease, decreased risk of type i diabetes, and increased risk of multiple malignancies in patients with ad. conclusion: there is likely a diversity of phenotypes for patterns of allergic disease. both positive and negative associations identified in this systematic review suggest that ad is condition with varied systemic manifestations. abstract background skin considered the classical presentation of atopic disease2. however, recent evidence suggests that this paradigm may not hold true for a significant portion of patients with these conditions3. not only is the timing of development likely more complex than previously believed, the comorbidities associated with ad are possibly more numerous and varied4. because ad is an inflammatory disease characterized by ongoing t-cell activation and cytokine production, it stands to reason that its mediators could have an effect on multiple extracutaneous organ systems. if the mechanisms underlying atopic disease do indeed play a role in the development of non-atopic comorbidities, it would support the notion put forth by brunner et al. (2016) that ad should be regarded as a systemic disease. the body of evidence behind this idea is rapidly expanding, with associations between ad and autoimmune, infectious, cardiovascular, neuro-psychiatric, and gastrointestinal disease becoming more well defined. however, there has not been a systematic review on this topic to date. we conducted a two-part systematic search of the literature on ad and extracutaneous disease. the first part involved a targeted search of pubmed (medline + cochrane library) and embase. in both of these databases “atopic dermatitis” and “atopic eczema” were searched in conjunction with various keywords representing the concept of systemic nature of disease (table 1). the second part of the systematic search process was a hand search of all recent abstracts accepted by the aad and eadv and abstracts published in 5 key journals (journal of the american academy of dermatology, journal of the european academy of dermatology and venereology, british journal of dermatology, american journal of clinical dermatology, and the journal of allergy and clinical immunology) within the past 2 years. all hits returned by both parts of the search process were screened for possible inclusion. narrative reviews, single-case studies, animal studies, editorials, non-english articles, and articles published prior to 1996 (greater than 20 years old) were excluded in a first review. next, titles and abstracts were screened for relevance to the research question. finally, all included articles were rated for quality of evidence with a newcastle-ottowa score5. this scale was chosen because the majority of included articles were case-control or cohort studies. the numbers of references obtained after each step of the search process are detailed in table 2. the final yield of the two-step, systematic search was 65 articles. these consisted of 41 case-control studies (63.1%), 19 cohort studies (29.2%), and 5 meta-analyses (7.7%). mean star ratings on the newcastle ottowa scale for case-control studies were: selection 2.44, comparability 1.56, and exposure 2.21. for cohort studies, mean ratings were 3.26, 1.63, and 2.37, respectively. non-atopic comorbidities identified in these studies included autoimmune disease, cardiovascular disease, gastrointestinal disease, neuro psychiatric disease, infectious disease, and malignancy. all distinct associated conditions identified during the search process are discussed below; when multiple studies revealed a positive association with a comorbidity, those with the highest newcastle ottowa score were cited. july 2017 volume i issue i copyright 2017 the national society for cutaneous medicine 9 methods results copyright 2017 the national society for cutaneous medicine 10 skin concept keywords/phrases atopic dermatitis atopic dermatitis atopic eczema systemic nature of disease systemic, inflammat* epidemiology, etiology comorbid* autoimmun*, immun*, cytokine activation atopic march, food allergy, asthma cardiovascular, gastrointestinal, neuro-psychiatric, malignancy table 1. keywords used in systematic search process. truncation symbols are represented by asterisk. july 2017 volume i issue i figure 1. eczema herpeticum. this vesicular eruption is caused by viral infection, typically hsv, of preexisting atopic dermatitis. figures/tables skin july 2017 volume i issue i copyright 2017 the national society for cutaneous medicine 11 results obtained in this review support the notion that the development of various allergic diseases is a dynamic process. there are numerous studies that describe the relationship among ad, asthma, food allergy, hay fever, allergic rhinitis, and atopic ophthalmic disease. while the “atopic march” pattern is prevalent, there is evidence that it may represent only one particular phenotype of allergic disease6. additionally, development of one allergic disease does not dictate which additional diseases might develop or when7. this apparent variability of phenotypes is worth mentioning before any discussion of non-atopic comorbidities, as it is possible that each one produces distinct extracutanous disease. autoimmune disease: the most well studied autoimmune disease investigated with ad is type i diabetes mellitus. the great majority of the evidence, including the study with the highest newcastle ottowa score, supports an inverse relationship between ad and type i diabetes8. in other words, children with insulin-dependent diabetes are less likely to suffer from eczema. this is thought to be due to negative interaction between th1 and th2 subsets9. interestingly, no association was shown between diabetes and asthma or hay fever. there is less data available on the association between ad and other autoimmune diseases. two studies provide conflicting evidence on its relationship with lupus erythematosus10, 11, although the study showing a positive association is both more recent and higher quality by newcastle ottowa score. finally, there is one cohort study suggesting that ad may be a risk factor for rheumatoid arthritis12. cardiovascular disease: the data on cardiovascular disease and risk factors in the ad population are more heterogeneous. evidence was mixed on the association between ad and increased bmi or hypertension. however, one study demonstrated an increased prevalence of coronary artery disease in ad patients using ct angiography13. the highest-scoring study related to cardiovascular disease demonstrated an increased risk of adverse cardiovascular outcomes in a cohort of 145,372 patients, including myocardial infarction, ischemic stroke, and cardiovascular death14. a possibly related comorbidity, erectile dysfunction, was observed in a case-control study to occur more frequently in ad patients15. interestingly, one study showed an association between ad and iga vasculitis in children16. for all of these cardiovascular conditions, further studies are needed to clarify the role of lifestyle and psychosocial factors in their development. gastrointestinal disease: there is extensive literature on the relationship between ad and food allergy, as discussed above. however, less information is available on non-allergic gastrointestinal disease. one case-control study examined various gastrointestinal symptoms in the pediatric ad population and found an increased incidence of vomiting, regurgitation, and diarrhea17. there is also emerging evidence supporting the role of the intestinal microbiome in the development of ad and the possibility of probiotic use in therapy18. there is one case-control study showing that children with ad are predisposed to develop fatty liver, but further investigation is needed19. finally, the cohort study mentioned above suggests that, in addition to being a risk factor for rheumatoid arthritis, ad might also be a risk factor for inflammatory bowel disease12. neuro-psychiatric disease: there is a significant body of evidence supporting an association between ad and autism spectrum and attention deficit hyperactivity disorders (asd, adhd). one retrospective cohort study discussion skin july 2017 volume i issue i copyright 2017 the national society for cutaneous medicine 12 of 21,756 patients demonstrated that ad occurring before the age of 3 increased the risk of developing both of these conditions20. additionally, increased rates of depression, anxiety, somatization, and injury requiring medical attention have been observed in multiple case-control studies21-23. these associations are often positively correlated with severity of ad. one possible explanation for these phenomena is sleep disturbance in ad patients. a case-control study found that inadequate sleep persists even when patients are in clinical remission24. malignancy: multiple high-quality studies analyze the risk of cancer in patients with ad. there is consistent evidence that ad patients are at increased risk for lymphoma, squamous cell carcinoma, and basal cell carcinoma25-27. however, a case-control study of 13,687 patients found that the increased risk of lymphoma was correlated with length of treatment with topical corticosteroids27. further studies are therefore needed to disentangle the effects of disease and the effects of treatment on skin cancer risk. there is conflicting evidence regarding other types of cancer. for instance, there is low-quality evidence of both increased and decreased risk of central nervous system malignancy in the ad population28, 29. a meta-analysis focusing on leukemia noted that available data were also quite heterogeneous30. it did, however, find a significant inverse relationship between ad and all. future high-quality cohort studies are needed to evaluate the risk of these malignancies. infectious disease: it is well documented that patients with ad are at increased risk for certain cutaneous infections due to the compromised barrier function of the skin. these classically include staphylococcus aureus, herpesvirus (fig. 1), and cocksackivirus. however, studies identified in this literature review also provided evidence for association with warts, molluscum, otitis media, and dental caries31-34. it is worth noting a case series that did not meet inclusion criteria for this review, which described an increased incidence of infectious endocarditis in ad patients35. because of the severity of this possible comorbidity, a case control or cohort study is recommended. the results of this systematic review support the notion that atopic dermatitis is strongly associated with other atopic diseases, including asthma, hay fever, and allergic rhinoconjunctivitis. however, it also suggests that the classical paradigm of the “atopic march” does not apply to all patients with atopic dermatitis. there is likely a diversity of phenotypes for patters of allergic disease. our analysis supports a significant association between ad and multiple neuro psychiatric comorbidities, particularly asd and adhd. additional themes supported by lower-level evidence are increased risk of cardiovascular disease, decreased risk of type i diabetes, and increased risk of multiple malignancies in patients with ad. in conclusion, the systemic manifestations of ad are likely multifactorial, resulting from both the inflammatory disease itself and associated lifestyle factors. conflict of interest disclosures: dr. emma guttman-yassky has served on advisory boards for abbvie, anaco, celgene, demira, galderma, glenmark, leo pharmaceuticals, medimmune, novartis, pfizer, regeneron, sanofi, stiefel/glaxosmithkline, vitae, mitsubishi tanabe, eli lilly, asana biosciences, kiowa kirin, and almirall corresponding author: dr. emma guttman-yassky address: 5 east 98th street, 5th floor, new york, ny 10029 phone: 212-241-9728 fax: 212-987-1197 email: emma.guttman@mountsinai.org conclusions skin july 2017 volume i issue i copyright 2017 the national society for cutaneous medicine 13 references: 1. leung dy. atopic dermatitis: new insights and opportunities for therapeutic intervention. journal of allergy and clinical immunology. 2000 may 31;105(5):860-76. 2. spergel jm, paller as. atopic dermatitis and the atopic march. journal of allergy and clinical immunology. 2003 dec 31;112(6):s118-27. 3. belgrave dc, granell r, simpson a, guiver j, bishop c, buchan i, henderson aj, custovic a. developmental profiles of eczema, wheeze, and rhinitis: two population-based birth cohort studies. plos med. 2014 oct 21;11(10):e1001748. 4. brunner pm, silverberg ji, guttman-yassky e, paller as, kabashima k, amagai m, luger ta, deleuran m, werfel t, eyerich k, stingl g. increasing comorbidities suggest that atopic dermatitis is a systemic disorder. journal of investigative dermatology. 2017 jan 31;137(1):18-25. 5. peterson j, welch v, losos m, tugwell p. the newcastle-ottawa scale (nos) for assessing the quality of nonrandomised studies in meta-analyses. 6. illi s, von mutius e, lau s, nickel r, gruber c, niggemann b, et al. the natural course of atopic dermatitis from birth to age 7 years and the association with asthma. the journal of allergy and clinical immunology. 2004;113(5):925-31. 7. barberio g, pajno gb, vita d, caminiti l, canonica gw, passalacqua g. does a 'reverse' atopic march exist? allergy: european journal of allergy and clinical immunology. 2008;63(12):1630-2. 8. decreased prevalence of atopic diseases in children with diabetes. the eurodiab substudy 2 study group. the journal of pediatrics. 2000;137(4):470-4. 9. olesen ab, juul s, birkebaek n, thestrup-pedersen k. association between atopic dermatitis and insulin dependent diabetes mellitus: a case-control study. lancet (london, england). 2001;357(9270):1749-52. 10. sekigawa i, yoshiike t, iida n, hashimoto h, ogawa h. allergic disorders in systemic lupus erythematosus: prevalence and family history. lupus. 2002;11(7):426-9. 11. sekigawa i, yoshiike t, iida n, hashimoto h, ogawa h. allergic disorders in systemic lupus erythematosus: prevalence and family history. lupus. 2002;11(7):426-9. 12. schmitt j, schwarz k, baurecht h, hotze m, folster-holst r, rodriguez e, et al. atopic dermatitis is associated with an increased risk for rheumatoid arthritis and inflammatory bowel disease, and a decreased risk for type 1 diabetes. the journal of allergy and clinical immunology. 2016;137(1):130-6. 13. hjuler kf, bottcher m, vestergaard c, deleuran m, raaby l, botker he, et al. increased prevalence of coronary artery disease in severe psoriasis and severe atopic dermatitis. the american journal of medicine. 2015;128(12):1325-34.e2. 14. andersen ym, egeberg a, gislason gh, hansen pr, skov l, thyssen jp. risk of myocardial infarction, ischemic stroke, and cardiovascular death in patients with atopic dermatitis. the journal of allergy and clinical immunology. 2016;138(1):310-2.e3. 15. chung sd, keller jj, lin hc. association of erectile dysfunction with atopic dermatitis: a population-based case-control study. the journal of sexual medicine. 2012;9(3):679-85. 16. wei cc, lin cl, shen tc, li tc, chen ac. atopic dermatitis and association of risk for henoch schonlein purpura (iga vasculitis) and renal involvement among children: results from a population-based cohort study in taiwan. medicine. 2016;95(3):e2586. 17. caffarelli c, cavagni g, deriu fm, zanotti p, atherton dj. gastrointestinal symptoms in atopic eczema. archives of disease in childhood. 1998;78(3):230-4. 18. penders j, gerhold k, stobberingh ee, thijs c, zimmermann k, lau s, et al. establishment of the intestinal microbiota and its role for atopic dermatitis in early childhood. the journal of allergy and clinical immunology. 2013;132(3):601-7.e8. 19. kimata h. fatty liver in atopic dermatitis. allergy. 2001 may 1;56(5):460. 20. chen mh, su tp, chen ys, hsu jw, huang kl, chang wh, chen tj, pan tl, bai ym. is atopy in early childhood a risk factor for adhd and asd? a longitudinal study. journal of psychosomatic research. 2014 oct 31;77(4):316-21. 21. garg n, silverberg ji. association between childhood allergic disease, psychological comorbidity, and injury requiring medical attention. annals of allergy, asthma & immunology : official publication of the american college of allergy, asthma, & immunology. 2014;112(6):525-32. skin july 2017 volume i issue i copyright 2017 the national society for cutaneous medicine 14 22. garg n, silverberg ji. association between childhood allergic disease, psychological comorbidity, and injury requiring medical attention. annals of allergy, asthma & immunology : official publication of the american college of allergy, asthma, & immunology. 2014;112(6):525-32. 23. schmitt j, apfelbacher c, chen cm, romanos m, sausenthaler s, koletzko s, et al. infant-onset eczema in relation to mental health problems at age 10 years: results from a prospective birth cohort study (german infant nutrition intervention plus). the journal of allergy and clinical immunology. 2010;125(2):404-10. 24. reuveni h, chapnick g, tal a, tarasiuk a. sleep fragmentation in children with atopic dermatitis. archives of pediatrics & adolescent medicine. 1999;153(3):249-53. 25. jensen ao, svaerke c, farkas dk, olesen ab, kragballe k, sørensen ht. atopic dermatitis and risk of skin cancer. american journal of clinical dermatology. 2012 feb 1;13(1):29-36. 26. arana a, wentworth ce, fernández-vidaurre c, schlienger rg, conde e, arellano fm. incidence of cancer in the general population and in patients with or without atopic dermatitis in the uk. british journal of dermatology. 2010 nov 1;163(5):1036-43. 27. arellano fm, arana a, wentworth ce, fernández vidaurre c, schlienger rg, conde e. lymphoma among patients with atopic dermatitis and/or treated with topical immunosuppressants in the united kingdom. journal of allergy and clinical immunology. 2009 may 31;123(5):1111-6. 28. hwang cy, chen yj, lin mw, chen tj, chu sy, chen cc, lee dd, chang yt, wang wj, liu hn. cancer risk in patients with allergic rhinitis, asthma and atopic dermatitis: a nationwide cohort study in taiwan. international journal of cancer. 2012 mar 1;130(5):1160-7. 29. deckert s, kopkow c, schmitt j. nonallergic comorbidities of atopic eczema: an overview of systematic reviews. allergy. 2014 jan 1;69(1):37-45. 30. linabery am, jurek am, duval s, ross ja. the association between atopy and childhood/adolescent leukemia: a meta-analysis. american journal of epidemiology. 2010 apr 1;171(7):749-64. 31. silverberg ji, silverberg nb. childhood atopic dermatitis and warts are associated with increased risk of infection: a us population-based study. journal of allergy and clinical immunology. 2014 apr 30;133(4):1041-7. 32. hayashida s, furusho n, uchi h, miyazaki s, eiraku k, gondo c, tsuji g, hachisuka j, fukagawa s, kido m, nakahara t. are lifetime prevalence of impetigo, molluscum and herpes infection really increased in children having atopic dermatitis?. journal of dermatological science. 2010 dec 31;60(3):173-8. 33. ibáñez md, valero al, montoro j, jauregui i, ferrer m, dávila i, bartra j, cuvillo a, mullol j, sastre j. analysis of comorbidities and therapeutic approach for allergic rhinitis in a pediatric population in spain. pediatric allergy and immunology. 2013 nov 1;24(7):678-84. 34. silverberg ji, hanifin jm. adult eczema prevalence and associations with asthma and other health and demographic factors: a us population–based study. journal of allergy and clinical immunology. 2013 nov 30;132(5):1132-8. 35. fukunaga n, okada y, konishi y, murashita t, koyama t. pay attention to valvular disease in the presence of atopic dermatitis. circulation journal. 2013;77(7):1862-6. skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 560 brief article bilateral nodules on the thighs: a case report on insulin therapy-induced palisaded granulomas chelsea d. harper, do1, jonathan crane, do, faad, faocd1, muammar arida, md, fca2, tara snow, oms-11, sabiha uddin, oms-11 1campbell university school of osteopathic medicine, wilmington, nc 2 dermpath diagnostics, pompano beach, fl as the incidence and prevalence of diabetes mellitus is increasing, more cases of dermatologic complications attributed to therapy are being reported. lipoatrophy, lipohypertrophy and injection site reactions, most commonly erythema, edema and induration, have been associated with subcutaneous insulin therapy1,2. available literature indicates that for some patients, insulin absorption can be abnormal if it is administered into the altered tissue1. therefore, an accurate diagnosis is important to guide clinical management. herein, we present an unusual case of bilateral nodules on the thighs secondary to insulin injections. a 90-year-old female presented with a 14year history of slowly enlarging pruritic nodules located on her proximal lateral thighs where insulin injections were repeatedly administered. past medical history is significant for diabetes mellitus type 2 managed with twice daily insulin detemir and aspart. physical exam revealed bilateral edematous, mobile, 8 x 10-cm nodules with central induration, hyperpigmentation and lichenification (figure 1). figure 1. a) soft, mobile nodules on both proximal, lateral thighs. b) 8 x 10-cm soft, mobile nodule with overlying hyperpigmentation and lichenification. the patient only injected insulin into the two sites and did not inject at any other site. the lesions had not previously been treated. the patient otherwise felt well and denied abstract as the incidence and prevalence of diabetes mellitus is increasing, more cases of dermatologic complications attributed to therapy are being reported. injection site reactions, most commonly erythema, edema and induration, lipohypertrophy, and lipoatrophy have been associated with subcutaneous insulin therapy. accurate diagnosis is important to guide clinical management and to ensure appropriate blood glucose control. herein, we present an unusual case of bilateral nodules on the thighs secondary to insulin injections. introduction case report a b skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 561 experiencing fevers, sweats, chills, weight loss, or malaise. a 4mm punch biopsy was performed on the right lateral thigh for further evaluation. histopathologic evaluation revealed a patchy dense inflammatory infiltrate composed of lymphocytes, plasma cells, eosinophils and irregular aggregates of monoand multinucleated histiocytes surrounding areas of degenerated hyalinized collagen bundles. this process involved the full thickness of the dermis (figure 2). figure 2. a) hematoxylin-eosin-stained sections reveal a patchy dense inflammatory infiltrate throughout the dermis b) high-power magnification revealed a mixed infiltrate with areas of degenerated hyalinized collagen bundles surrounded by mono and multinucleated histiocytes. the epidermis showed slight acanthosis and compact orthokeratosis. special stains for fungi and acid fast organisms (pas and fite) were negative for organisms. amyloid stains (congo red and crystal violet) were also negative. there were no abnormalities in size or morphology of the adipocytes, and no foreign bodies were identified on polarized light microscopy. in view of the clinical history and histopathologic findings, the patient was diagnosed with a palisaded granulomatous reaction induced by insulin injections. at the follow up appointment after rotating multiple other injection sites, she has not developed any other granulomas. more cases of dermatologic complications attributed to insulin therapy are being reported with the concurrent increase in diabetes mellitus1,2. the most common complications secondary to insulin injection are erythema, edema, and induration. uncommon complications are lipohypertrophy, and lipoatrophy. rare injection-site complications include insulinderived amyloidosis, systemic allergic reaction, non-palisaded granulomas and suppurative granulomas3-5. one case in the literature reports a foreign body reaction to insulin with a palisaded granulomatous dermatitis2. clinically, the main diagnoses to consider in the differential of insulin-induced palisaded granuloma are insulin-induced nodular amyloidosis and insulin-induced lipohypertrophy5,6. histologically, nodular amyloidosis will demonstrate eosinophilic material, fibrosis, scattered inflammatory cells and will stain positive for congo red. lipohypertrophy will display mature adipocytes with lipid droplets and fibrosis2,5. a number of dermatologic conditions have been related to diabetes mellitus or as a consequence of therapies used in the treatment of diabetes. educating patients on how to prevent potential treatment-related complications is important as there are limited treatment options. understanding the various cutaneous adverse effects of insulin therapy is also important since insulin absorption from abnormal tissue can alter absorption and lead to difficulties in achieving appropriate blood glucose control6,7. therefore, accurate diagnosis is important to guide clinical management which includes careful monitoring of blood glucose levels and rotating injection sites. as the incidence of insulin-induced granulomas is rare, there is minimal literature addressing treatment for early and late presentations. due to the dermal and subcutaneous localization of the pathology, topical steroids and steroid-sparing agents discussion a b skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 562 would likely be ineffective for treatment. if the patient refuses to rotate injection sites, surgical excision should be considered for optimal glucose absorption or if immediate cosmesis is sought5-7. with the increase in diabetes mellitus, there is a concurrent increase in cutaneous complications related to diabetes mellitus treatment. cutaneous complications from insulin therapy can have important ramifications for cosmesis and, most importantly, glycemic control. accurate diagnosis, judicious blood glucose monitoring and patient education are paramount. conflict of interest disclosures: none funding: none corresponding author: tara j. snow campbell university school of osteopathic medicine 75 winston dr. lillington, nc 27546 phone: (616) 432-7812 email: tjsnow0505@email.campbell.edu references: 1. richardson t, kerr d. skin-related complications of insulin therapy: epidemiology and emerging management strategies. am j clin dermatol. 2003;4(10):661-667. [doi:10.2165/00128071200304100-00001] 2. motaparthi k. palisaded granulomatous dermatitis secondary to recombinant insulin. j cutan pathol, 2017;44:509-511. [doi:10.1111/cup.12916] 3. tanizaki h, matsumura y, tokura y, miyachi y, kabashima k. a case of suppurative granuloma induced by insulin injection. acta derm venereol. 2010;90(5):540-541. [doi:10.2340/00015555-0897] 4. mangla a, kim gj, agarwal n, et al. localized insulin amyloidosis with use of concentrated insulin: a potential complication. diabet med. 2016;33(12):e32-e35. [doi:10.1111/dme.13137] 5. ansari am, osmani l, matsangos ae, li qk. current insight in the localized insulin-derived amyloidosis (lida): clinico-pathological characteristics and differential diagnosis. pathol res pract. 2017;213(10):1237-1241. [doi:10.1016/j.prp.2017.08.013] 6. al ajlouni m, abujbara m, batieha a, ajlouni k. prevalence of lipohypertrophy and associated risk factors in insulin-treated patients with type 2 diabetes mellitus. int j endocrinol metab. 2015;13(2):e20776. published 2015 apr 30. [doi:10.5812/ijem.20776] 7. johansson ub, amsberg s, hannerz l, et al. impaired absorption of insulin aspart from lipohypertrophic injection sites. diabetes care. 2005;28(8):2025-2027. [doi:10.2337/diacare.28.8.2025] conclusion mailto:tjsnow0505@email.campbell.edu acknowledgements study funded by galderma r&d; poster/editorial support provided by galderma laboratories, l.p. introduction cleansing skin is an important component of maintaining healthy skin as it removes dirt, oil, make up, and helps prepare the skin for topical prescription treatments. however, it can also damage the skin by stripping out natural moisturizing factors and degrading skin barrier function. for patients with rosacea, this is of particular concern due to underlying skin barrier disruption and increased skin sensitivity to many ingredients found in cleansing products. a foaming cleanser has been specifically developed for redness-prone skin (cetaphil foaming face wash [cffw]). this formula contains caffeine, allantoin, and glycerin to help preserve the skin barier. the results of 2 clinical studies that assessed the performance and tolerability of cffw are presented in this poster. subjects and methods study 1: hydration and skin barrier function • men and women with dry volar forearms • product massaged onto pre moistened skin and left for 1 minute • product was rinsed with 50 ml of warm water and blotted dry control had same rinsing and drying procedures • corneometer and transepidermal water loss (tewl) assessed at baseline and 2, 4, 8, and 24 hourss study 2: in use efficacy and tolerability • men or women with rosacea and mild to moderate non-transient erythema • product used bid for 3 weeks • assessments made on day 1, day 1 30 minutes after first use and days 8 and 22 before product use chromameter, investigator, and subject assessment of redness investigator and subject tolerability (dermatologic and ophthalmologic) assessments · redness and tolerability assessments made on a 5 point scale of 0 (none), 0.5 (very slight), 1 (slight), 2 (moderate) and 3 (strong) subject satisfaction an effective yet gentle foaming facial cleanser specifically designed for redness-prone skin matthew h meckfessel, phd1; sandrine teissedre, msc2; nadege lachmann3; francine santoro, md3 1galderma laboratories, l.p., fort worth, texas; 2galderma r&d, sophia antipolis, france; 3galderma r&d, egerkingen, switzerland cet.p-rd105309-01 summary cffw provides effective, yet gentle cleansing, and is an ideal facial cleanser for patients with rosacea m ea n sc or e (a .u .) chromameter baseline day 1, 30 minutes day 8 day 22 0 10 5 15 20 25 * *p < .05 vs baseline figure 4. chromameter assessment disagree neutral agree percent of subjects overall, i like the product very much is suitable for sensitive skin washes away face make up and skin impurities rinses easily to leave skin soft and clean 0 50 6010 20 30 40 70 80 90 100 24.2 69.7 66.7 3.0 3.0 3.0 3.0 21.2 9.1 15.2 78.8 90.9 p < .05 for agree vs disagree for all figure 5. subject satisfaction results there were no significant changes to skin hydration or skin barrier function during the 24 hour period showing cffw did not disrupt the skin barrier (figures 1 and 2). for the in use study, 33 women enrolled with a mean age of 52.1 years. there was no significant change during the study as assessed by investigators and subjects (figure 3). there was a significant worsening as assessed by chromameter at day 8 (figure 4). however, this change in erythema is likely not clinically relevant as they were not noted by the investigator or subjects. the product was well tolerated with mean scores for all parameters less than mild for both dermatologic and ophthalmologic assessments (data not shown). subjects demonstrated high satisfaction with the product (figure 5). three adverse events were reported and were not considered related by the investigator: toothache, suspicion of nervous breakdown, and edema of both lower lids. m ea n co rn eo m et er (a .u .) ccfw control area hour 0 20 22 24 26 28 30 32 34 36 38 40 4 8 12 16 20 24 no significant differences between control and cffw m ea n te w l (g /m 2h ) ccfw control area hour 0 0 2 4 6 8 10 4 8 12 16 20 24 no significant differences between control and cffw m ea n sc or e investigator subject baseline day 1, 30 minutes day 8 day 22 0 1 2 3 no significant differences from baseline. figure 2. tewl assessments figure 1. corneometry assessments figure 3. skin redness assessments fc17postergaldermameckfesseleffectivefoamingcleanser.pdf skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 132 research letter weekly isotretinoin therapy (wit) study: a potential alternative for the treatment of moderate acne vulgaris samantha karlin, md1, alexandra ritter, bs1, courtney linkous, bs1, katherine wehlage, md1, lara wine lee, md1 1medical university of south carolina, charleston, sc current treatment options for moderate acne vulgaris remain limited and usually include long courses of oral antibiotics. nagler et al. found that the average antibiotic use for moderate-to-severe acne prior to receiving isotretinoin was 331 days, with 88% requiring treatment for six months or more, and 46% for at least one year.1 males are especially limited in their treatment options as they are not eligible for hormonal management. consequently, there is a need for further research on alternative moderate acne treatment options. the efficacy of isotretinoin has been wellestablished; however, there are numerous reported side-effects, such as severe dry skin, lips, and eyes, as well as liver enzyme and lipid abnormalities, thought to be caused by achieving the cumulative dose rapidly via once to twice daily dosing. studies have explored alternative isotretinoin dosing regimens, including microdose and lower daily dose regimens,2,3 and daily dosing for only 7-10 consecutive days out of each month.3,4 these studies had favorable outcomes with fewer to similar adverse effect rates compared to conventional dosing. despite the lower total cumulative dose achieved versus with conventional dosing, recurrence rates were similar.3 additionally, cost of alternative dosing was lower than conventional dosing, and patient satisfaction was highest in the alternative dosing groups.2-4 abstract background: treatment options for moderate acne remain limited. methods: we evaluated the efficacy of once-weekly dosed isotretinoin for moderate acne. nineteen participants took isotretinoin dosed at 1-1.5 mg/kg/week for four months. patient clinical improvement, quality of life, and adverse effects were measured at baseline and at monthly follow-up visits. laboratory monitoring was performed at baseline and after two months. results: ninety-five percent of patients (18/19) had improvement in their acne. the majority (68%) went from a baseline of moderate acne (score 3) to either clear (score 0) or almost clear (score 1) by the end of four months. there were no major lab abnormalities or adverse events. eighty-nine percent of patients (17/19) reported improvement in their quality of life. conclusion: once weekly isotretinoin may be an additional treatment option for patients with moderate acne. introduction skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 133 figure 1. results from 19 participants taking once weekly isotretinoin for a four month study period showing improvement in acne in 95% of patients (18/19), with the majority (68%) going from a baseline of moderate acne (score 3) to either clear (score 0) or almost clear (score 1). the teenage boy participant who initially worsened, then improved, and ended at his baseline is now on twice weekly isotretinoin at 1 mg/kg/dose with acne clearance after two months. in this irb-approved study, we evaluated the efficacy of once weekly dosed isotretinoin (1-1.5 mg/kg/week) as a potential therapy for moderate acne. nineteen patients (10 females, 9 males) aged 12-43 years completed the four-month study period. participants could not be on spironolactone or oral antibiotics commonly used for acne, but could use over-thecounter topicals. two surveys, the validated dermatology quality of life index (dqli) and one created to assess potential sideeffects, were administered at baseline and at monthly follow-up visits. laboratory monitoring (complete blood count, comprehensive medical panel, and lipid panel) was completed at baseline and after two months. efficacy was determined by comparing baseline and monthly clinical photograph scores; photographs were graded by a blinded researcher using the validated comprehensive acne severity scale. after the study period, participants could choose to follow-up for two months while either continuing or discontinuing the medication. ninety-five percent of patients (18/19) had improvement in their acne. the majority methods results skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 134 (68%) went from a baseline of moderate acne (score 3) to either clear (score 0) or almost clear (score 1) by the end of four months. five patients chose to continue once weekly isotretinoin after the study period; at their two-month follow-up photographs, four patients were clear (0) and one patient almost clear (1). four patients who elected to discontinue isotretinoin after the study remain clear (0), one patient almost clear (1), one patient mild (2), and one patient back to baseline (3) after two months. the participant who ended back at his baseline achieved acne clearance after two months of twice weekly isotretinoin. there were no major lab abnormalities or adverse events. eighty-nine percent of patients (17/19) had an improvement in their dqli, with twelve patients achieving a score of 0 by the end of the study (the presence of acne having no effect on one’s quality of life). the most common side-effects were mild dry skin; eleven participants had continued dry skin from baseline and one participant endorsed new, mild dry skin. additionally, seven patients had continued dry eyes/lips, and three reported new, mild dry eyes/lips. three participants endorsed new mild myalgias after four months. figure 2 a) patient with moderate acne at baseline, prior to beginning the study. b) same patient after four months of once weekly isotretinoin (1-1.5 mg/kg/week). no acneiform lesions, just mild postinflammatory hyperpigmentation. study findings suggest that once weekly isotretinoin dosing for male and female patients with moderate acne is a potential alternative to oral antibiotics and hormonal therapies. study replication using a larger patient population and clinical trials exploring alternative dosing regimens for isotretinoin are recommended. note: photographs used with permission conflict of interest disclosures: none funding: none corresponding author: samantha karlin, md medical university of south carolina dept. of dermatology and dermatologic surgery 135 rutledge ave charleston, sc email: karlin@musc.edu references: 1. nagler ar, milam ec, orlow sj. the use of oral antibiotics before isotretinoin therapy in patients with acne. j am acad dermatol. 2016;74(2):273‐ 279. doi:10.1016/j.jaad.2015.09.046 2. rademaker m, wishart jm, birchall nm. isotretinoin 5 mg daily for low-grade adult acne – a placebo-controlled, randomized double-blind study. jeadv. 2014;28:747–54. 3. lee jw, yoo kh, park ky, han ty, li k, seo sj, hong ck. effectiveness of conventional, lowdose and intermittent oral isotretinoin in the treatment of acne: a randomized, controlled comparative study. br j dermatol. 2011;164(6):1369. epub 2011 may 17. 4. kaymak y, ilter n. the effectiveness of intermittent isotretinoin treatment in mild or moderate acne. j eur acad dermatol venereol. 2006;20:1256–60 conclusion a .. b .. mailto:karlin@musc.edu objective to assess the efficacy of bimekizumab (bkz), compared with secukinumab (sec), across different subgroups of patients with moderate to severe plaque psoriasis. introduction • bkz is a monoclonal igg1 antibody that selectively inhibits interleukin (il)-17f in addition to il-17a.1 • in be radiant (nct03536884), an ongoing phase 3b, randomized, double-blinded, active comparator-controlled trial, superior levels of complete skin clearance (pasi 100 [100% improvement from baseline in psoriasis area and severity index]) for patients with plaque psoriasis were observed with bkz compared with sec, a biologic targeting il-17a only.2 • response to treatment with biologics can vary depending on patient characteristics.3 • here, we assess the efficacy of bkz vs sec across subgroups of patients enrolled in be radiant over 48 weeks. methods • patients received treatment as shown in figure 1. • proportions of patients achieving pasi 100 and pasi 90 (≥90% improvement from baseline in psoriasis area and severity index) at week 48 are reported for relevant patient subgroups including baseline weight, prior biologic exposure, age, psoriasis disease duration prior to baseline, baseline pasi, and baseline investigator’s global assessment (iga). • analyses are based on the intention-to-treat (itt) population, with data for bkz every 4 weeks (q4w) and every 8 weeks (q8w) maintenance dosing regimens pooled. • missing data were imputed using non-responder imputation (nri). results • in be radiant, 373 patients were randomized to bkz and 370 were randomized to sec. • baseline characteristics were similar between the bkz and sec treatment arms (table 1). • at week 48, more bkzvs sec-treated patients achieved pasi 100 (figure 2). • this trend was reflected across patient subgroups, with pasi 100 responder rates ranging from 60.5–75.0% for bkz compared with 33.3–50.7% for sec-treated patients (figure 2). • similar trends across subgroups were seen for pasi 90 responses at week 48 for bkzvs sec-treated patients (figure 3). summary presented at the fall clinical dermatology conference 2021 | october 21–24 | las vegas, nv conclusions bkz demonstrated higher levels of near or complete skin clearance than sec at week 48 of treatment, regardless of baseline demographics, disease characteristics, or prior exposure to biologic therapies. given its consistent efficacy across all subgroups analyzed, these results support bkz as a treatment suitable for a wide variety of patients with psoriasis, including those with a high weight or severe disease. andrew blauvelt,1 lars iversen,2 sandy mcbride,3 melinda gooderham,4,5 petra staubach,6 paul yamauchi,7,8 fabienne staelens,9 veerle vanvoorden,9 katy white,10 paolo gisondi11 bimekizumab versus secukinumab efficacy across subgroups of patients with moderate to severe plaque psoriasis: results from the multicenter, randomized, double-blinded phase 3b be radiant trial previously presented at eadv 2021 figure 1 be radiant study design institutions: 1oregon medical research center, portland, or, usa; 2department of dermatology, aarhus university hospital, aarhus, denmark; 3royal free london nhs foundation trust, london, uk; 4skin centre for dermatology, probity medical research, on, canada; 5queen’s university, on, canada; 6university of mainz, mainz, germany; 7dermatology institute and skin care center, santa monica, ca, usa; 8division of dermatology, david geffen school of medicine at university of california, los angeles, ca, usa; 9ucb pharma, brussels belgium; 10ucb pharma, slough, uk; 11university of verona, verona, italy. references: 1glatt s. ann rheum dis 2017;77:523–32; 2reich k. n engl j med 2021; 385:142–52; 3edson-heredia e. j invest dermatol 2014;134:18–23. author contributions: substantial contributions to study conception/design, or acquisition/analysis/interpretation of data: ab, li, sm, mg, ps, py, fs, vv, kw, pg; drafting of the publication, or revising it critically for important intellectual content: ab, li, sm, mg, ps, py, fs, vv, kw, pg; final approval of the publication: ab, li, sm, mg, ps, py, fs, vv, kw, pg. author disclosures: ab: served as a scientific adviser and/or clinical study investigator for abbvie, abcentra, aligos, almirall, amgen, arcutis, arena, aslan, athenex, boehringer ingelheim, bristol myers squibb, dermavant, eli lilly, evommune, forte, galderma, incyte, janssen, landos, leo pharma, novartis, pfizer, rapt, regeneron, sanofi genzyme, sun pharma, ucb pharma, and vibliome. li: served as a consultant and/or paid speaker for and/or participated in clinical trials sponsored by abbvie, almirall, amgen, astrazeneca, bristol myers squibb, boehringer ingelheim, celgene, eli lilly, janssen, leo pharma, msd, novartis, pfizer, regranion, samsung, ucb pharma, and union therapeutics. sm: consultancy and/or speakers’ fees from abbvie, almirall, eli lilly, novartis, janssen, amgen, celgene and ucb pharma; grant/research support from abbvie and celgene. mg: investigator, speaker, consultant or advisory board member for abbvie, amgen, akros, arcutis, bausch health, bristol myers squibb, boehringer ingelheim, celgene, dermavant, dermira, eli lilly, galderma, gsk, janssen, kyowa kirin, medimmune, merck, novartis, pfizer, regeneron, sanofi genzyme, sun pharma and ucb pharma. ps: has received grants and/or personal fees from abbvie, amgen, almirall, boehringer ingelheim, bristol myers squibb, celgene, eli lilly, janssen, leo pharma, novartis, pfizer and ucb pharma. py: speaker, investigator and/ or consultant for abbvie, amgen, eli lilly, janssen, novartis, ortho dermatologics, sun pharma and ucb pharma. fs, vv, kw: employees and shareholders of ucb pharma. pg: consultant for abbvie, abiogen, almirall, celgene, eli lilly, janssen, leo pharma, merck, msd, novartis, otsuka, pfizer, pierre fabre, sanofi and ucb pharma. acknowledgements: this study was funded by ucb pharma. we thank the patients and their caregivers in addition to the investigators and their teams who contributed to this study. the authors acknowledge susanne wiegratz, msc, ucb pharma, monheim, germany for publication coordination, natalie nunez gomez, md, ucb pharma, brussels, belgium for critical review, carolyn walsh, phd, costello medical, cambridge, uk, for medical writing and editorial assistance and the design team at costello medical for graphic design assistance. all costs associated with development of this poster were funded by ucb pharma. bkz: bimekizumab; bsa: body surface area; dlqi: dermatology life quality index; ig: immunoglobulin; iga: investigator’s global assessment; il: interleukin; itt: intention-to-treat; nri: non-responder imputation; q4w: every 4 weeks; q8w: every 8 weeks; pasi: psoriasis area and severity index; sd: standard deviation; sec: secukinumab; tnf: tumor necrosis factor. figure 2 patients achieving pasi 100 responses at week 48 among baseline subgroups (nri; itt population) in be radiant (nct03536884), patients were randomized 1:1 to bkz 320 mg every 4 weeks (q4w) or sec 300 mg weekly to week 4 then q4w. patients randomized to bkz 320 mg q4w either continued to receive q4w dosing at week 16 or switched to q8w maintenance dosing. bkz-treated patients achieved higher levels of near or complete skin clearance at week 48 of treatment than sec-treated patients, regardless of patient subgroup. figure 3 patients achieving pasi 90 responses at week 48 among baseline subgroups (nri; itt population) overall pasi 100 response rates at week 48 have been reported previously.2 aincludes all patients randomized to bkz, regardless of whether they received bkz 320 mg q4w or q8w maintenance dosing from week 16. bincludes patients with multiple prior biologic use. canti-il-23 category does not include anti-il-12/23 therapies. baseline characteristics have been reported previously.2 aincludes patients with multiple prior biologic use. banti-il-23 category does not include anti-il-12/23 therapies. overall pasi 90 response rates at week 48 have been reported previously.2 aincludes all patients randomized to bkz, regardless of whether they received bkz 320 mg q4w or q8w maintenance dosing from week 16. bpatients with multiple biologics use are included. canti-il-23 category does not include anti-il-12/23 therapies. age and weight duration of disease disease severity prior biologic treatment subgroups analyzed table 1 be radiant baseline characteristics sec n=370 bkz n=373 age (years), mean ± sd 44.0 ± 14.7 45.9 ± 14.2 male, n (%) 235 (63.5) 251 (67.3) caucasian, n (%) 348 (94.1) 347 (93.0) weight (kg), mean ± sd 88.8 ± 20.0 90.1 ± 21.3 duration of disease (years), mean ± sd 17.2 ± 12.3 18.4 ± 13.1 pasi score, mean ± sd 19.7 ± 6.7 20.2 ± 7.5 bsa (%), mean ± sd 23.8 ± 14.3 24.8 ± 15.5 iga score, n (%) 3: moderate 268 (72.4) 240 (64.3) 4: severe 102 (27.6) 131 (35.1) dlqi score, mean ± sd 11.3 ± 7.2 10.8 ± 6.6 prior systemic therapy, n (%) 272 (73.5) 267 (71.6) prior biologic therapy,a n (%) 119 (32.2) 125 (33.5) anti-tnf 69 (18.6) 71 (19.0) anti-il-17 50 (13.5) 39 (10.5) anti-il-23b 23 (6.2) 24 (6.4) pasi 100 bkz overall response sec overall response response across subgroups response across subgroups 60.5% 75.0% 33.3% 50.7% – – 67.0% 46.2% pasi response at week 48 pasi 90 bkz overall response sec overall response response across subgroups response across subgroups 76.3% 89.5% 64.4% 78.3% – – 83.6% 70.5% week 162–5 weeks week 48 baseline screening bkz 320 mg q4w n=373 n=370 n=147 n=215 sec 300 mg q4w n=743 1:1 randomization bkz 320 mg q4w bkz 320 mg q8w active-comparator period initial treatment period maintenance period overall pasi 100 response rate: age (years) <40 40–<65 ≥65 baseline weight (kg) ≤100 >100 psoriasis disease duration <median [15.27 years] ≥median [15.27 years] baseline disease severity pasi <20 pasi ≥20 baseline iga score 3 4 prior systemic therapy yes no prior biologic exposureb yes no prior anti-tnf exposure yes no prior anti-il-17 exposure yes no prior anti-il-23 exposurec yes no proportion of patients (%) 0 30 40 50 60 70 80 90 100 74/151 81/180 16/39 142/283 29/87 96/195 75/175 110/235 61/135 136/268 35/102 127/272 44/98 53/119 118/251 34/69 137/301 22/50 149/320 11/23 160/347 49.0 45.0 41.0 50.2 33.3 49.2 42.9 46.8 45.2 50.7 34.3 46.7 44.9 44.5 47.0 49.3 45.5 44.0 46.6 47.8 46.1 92/133 135/202 23/38 178/264 72/109 124/174 126/199 153/233 97/140 161/240 87/131 175/267 75/106 84/125 166/248 43/71 207/302 27/39 223/334 18/24 232/349 69.2 66.8 60.5 67.4 66.1 71.3 63.3 65.7 69.3 67.1 66.4 65.5 70.8 67.2 66.9 60.6 68.5 69.2 66.8 75.0 66.5 n/n % n/n % sec 300 mg q4w (n=370) bkz totala (n=373) 46.2% 67.0% overall pasi 90 response rate: age (years) <40 40–<65 ≥65 baseline weight (kg) ≤100 >100 psoriasis disease duration <median [15.27 years] ≥median [15.27 years] baseline disease severity pasi <20 pasi ≥20 baseline iga score 3 4 prior systemic therapy yes no prior biologic exposureb yes no prior anti-tnf exposure yes no prior anti-il-17 exposure yes no prior anti-il-23 exposurec yes no proportion of patients (%) 0 50 60 70 80 90 100 109/151 125/180 27/39 205/283 56/87 140/195 121/175 167/235 94/135 194/268 67/102 192/272 69/98 83/119 178/251 49/69 212/301 38/50 223/320 18/23 243/347 72.2 69.4 69.2 72.4 64.4 71.8 69.1 71.1 69.6 72.4 65.7 70.6 70.4 69.7 70.9 71.0 70.4 76.0 69.7 78.3 70.0 119/133 164/202 29/38 223/264 89/109 154/174 158/199 188/233 124/140 199/240 111/131 222/267 90/106 104/125 208/248 58/71 254/302 32/39 280/334 19/24 293/349 89.5 81.2 76.3 84.5 81.7 88.5 79.4 80.7 88.6 82.9 84.7 83.1 84.9 83.2 83.9 81.7 84.1 82.1 83.8 79.2 84.0 n/n % n/n % sec 300 mg q4w (n=370) bkz totala (n=373) 70.5% 83.6% results: abstract background: tinea pedis is the most common dermatophyte infection. treatment is critical in order to alleviate pruritic symptoms, to reduce the risk for secondary bacterial infection, and to limit the spread of infection to other body sites or other individuals. topical antifungal foams are effective in treating interdigital tinea pedis, but little is known about how clinical efficacy of antifungal foams impact quality of life as compared to traditional antifungal creams. study design: a single-center, investigator blinded, observational split body, pilot study was conducted to compare econazole nitrate topical foam, 1% to ketoconazole cream 2%. all 20 subjects received econazole nitrate topical foam, 1% and ketoconazole cream 2% to either right or left foot for 14 days. improvements in patient quality of life and patient preference were measured using the pruritus visual analog scale 0/as), skindex-16, and patient preference questionnaires. results: nineteen subjects completed the study and one subject was lost to follow-up. both econazole nitrate topical foam, 1% and ketoconazole cream 2% were effective in reducing pruritic symptoms as measured by the pruritus vas. the reductions in vas exhibited by econazole nitrate topical foam, 1% were significantly greater than those exhibited by ketoconazole cream 2%. patient symptom, emotional, functional and total scores from the skindex-16 were significantly reduced by the final visit. patients did not exhibit a significant preference for either econazole nitrate topical foam, 1% or ketoconazole cream 2% on patient preference questionnaires. one adverse event was reported with no further details provided. conclusion: while patient preference was equal for the two study medications, econazole nitrate topical foam, 1% had increased reductions in pruritus vas scores compared to ketoconazole cream 2%. this suggests that econazole nitrate topical foam, 1% is both clinically effective and has meaningful improvements in patient quality of life. introduction • tinea pedis is the most common dermatophyte infection. results from the national ambulatory medical care survey (namcs) and national hospital ambulatory medical care survey (nhamcs) (1995-2004) indicated an average of 4,124,038 annual visits for dermatophytoses during the study period with tinea pedis accounting for 18.8% (1). • treatment is critical in order to alleviate pruritic symptoms, to reduce the risk for secondary bacterial infection, and to limit the spread of infection to other body sites or other individuals (2, 3). • topical antifungal foams are effective in treating interdigital tinea pedis, but little is known about how clinical efficacy of antifungal foams impact quality of life as compared to traditional antifungal creams. objective • to compare the efficacy of and patient preference for econazole nitrate topical foam, 1% versus those of ketoconazole cream 2% on the signs and symptoms of interdigital tinea pedis. subjects and methods study design • single-center, investigator blinded, observational, split body, pilot study • all subjects applied econazole nitrate topical foam, 1% (ecoza foam) and ketoconazole cream 2% (nizoral cream) to either the right or left foot. study medication was applied twice daily; once in the morning, and once in the evening. • the duration of the study was 14 days and consisted of a baseline visit and a final visit at the end of 14 days of treatment. subjects • male and female outpatients ≥18 years of age or older • pruritus visual analog scale (vas) score >5 • positive koh preparation at baseline • able to understand study requirements and sign informed consent/hipaa authorization forms • female patients of child-bearing potential were required to have a negative urine pregnancy test and to practice a reliable method of contraception throughout the study. assessments efficacy • pruritus vas: at each study visit, subjects assessed the severity of pruritus using a 10-cm vas with the left side of the scale anchored with “no itch” and the right side of the scale anchored with “worst imaginable itch”. • skindex-16: subjects completed the skindex-16 at baseline and the final study visit. the skindex-16 is a short 16-item patient-completed assessment using numerical analogue scales (0 = never bothered to 6 = always bothered). responses to the skindex-16 are categorized into three subscales: symptom, emotional, and functional (4). treatment preference • subjects also completed a treatment preference questionnaire at the end of the study. safety • subjects were monitored for signs and symptoms of adverse events (aes) throughout the study. data analysis • all analyses were conducted on an intent-to-treat population that included all subjects who were enrolled and received study medication. • descriptive statistics (mean, standard deviation, etc.) were provided for all continuous variables and frequencies for all categorical variables. • differences between study treatments were evaluated using analyses of covariance (ancova) with baseline values for variables measured as covariates. • all statistical tests were two-sided and interpreted at a 5% significance level. results subjects • twenty subjects (11 males, 9 females; 16 white, 4 black; age 46 ± 16 years [range = 18-68 years]) were enrolled. • ten subjects were randomly assigned to econazole nitrate topical foam, 1% on the left foot and ketoconazole cream 2% on the right foot; and 10 were randomized to receive econazole nitrate topical foam, 1% on the right foot and ketoconazole cream 2% on the left foot. • one subject was lost to follow-up and all efficacy analyses were based on results for 19 subjects. efficacy pruritus vas • there were substantial reductions from baseline in pruritus vas scores for both econazole nitrate topical foam, 1% (p=0.0001) and ketoconazole cream 2% (p=0.001) (figure 1). • the mean reduction observed for the feet treated with econazole nitrate topical foam, 1% was significantly greater than mean reduction observed for the feet treated with ketoconazole cream 2% (p=0.006) (figure 1). skindex-16 • there were significant decreases in the skindex-16 domain scores from baseline to the final visit (all p<0.01) (figure 2). • it should be noted that no econazole nitrate topical foam, 1% vs ketoconazole cream 2% comparisons were possible for the skindex-16 data, since all patients received both medications and the questions of the skindex-16 were not medication-specific. figure 1. results for pruritus vas 8.3 8.3 4.3 1.5 econazole nitrate topical foam, 1% ketoconazole cream, 2% baseline day 14 ‡ * p=0.0001 vs baseline; ‡ p=0.001 vs baseline, * † † p=0.006 vs ketoconazole cream, 2% error bars are standard deviations 10 9 m ea n p ru ri tu s va s 8 7 6 5 4 3 2 1 0 figure 2. results for skindex-16 totalfunctionalemotionalsymptom error bars are standard deviations p=0.0002 m ea n s ki nd ex -1 6 s co re s p=0.001 p=0.007 p=0.003 baseline day 146 5 4 3 2 1 0 3.4 3.0 3.0 3.8 1.5 1.7 0.9 1.6 subject ratings • there were no significant differences in patient preference on any item of the questionnaire between econazole nitrate topical foam, 1% and ketoconazole cream 2% (all p>0.05). • econazole nitrate topical foam, 1% had median ratings of good or excellent on all measures assessed (figure 3). figure 3. subject ratings of econazole nitrate topical foam, 1% easy to apply fragrance free spreadability lack of stickiness moisturizing lack of residue not greasy permitted continuation of activites easy to use median rating skin felt soft disappears quickly absorbs quickly 543210 5 = excellent 4 = good 3 = fair 2 = poor 1 = very poor safety • one ae was noted, but no further details were provided. conclusions • econazole nitrate topical foam, 1% was significantly superior to ketoconazole cream 2% for decreasing pruritus vas scores over 2 weeks of treatment in patients with tinea pedis. • treatment also significantly decreased skindex-16 total scores and scores for all domains comprising this measure. • subject rated econazole nitrate topical foam, 1% as good or excellent for all properties evaluated. • all of these results support the conclusion that econazole nitrate topical foam, 1% is clinically effective, easy to use, and provides meaningful improvements in patient quality of life. references 1. panackal aa, halpern ef, watson aj. int j dermatol. 2009;48(7):704-12. 2. sahoo ak, mahajan r. indian dermatol online j. 2016;7(2):77-86. 3. moriarty b, hay r, morris-jones r. the diagnosis and management of tinea. bmj. 2012;345:e4380. 4. chren mm, lasek rj, sahay ap, et al. j cuttan med surg. 2001;5(2):105-10. the effect of econazole nitrate topical foam, 1% on signs and symptoms (pruritus) of lnterdigital tinea pedis lauren k. hoffman1, isabelle raymond, phd2, leon kircik, md3,, 1 albert einstein college of medicine, bronx ny, 2 exeltis usa, florham park, nj, 3 mount sinai medical center, new york, ny, this study and medical writing support were funded by grants from exeltis usa dermatology acknowledgements: the authors would like to thank tom prunty, cmpp and bob rhoades, phd of aramed strategies for their assistance with medical writing services. fc17posterexeltishoffmaneffectofeconazole.pdf introduction z seborrheic keratoses (sks) are common cutaneous lesions that affect an estimated 84 americans,1 particularly those who are middle-aged and older. while benign, these lesions are cosmetically unacceptable to many patients z removal of sks is often performed for cosmetic reasons, but it may be indicated for inflamed, pruritic, or painful lesions z prior to december 2017, there was no us fda–approved drug for the treatment of sks. ablative/destructive procedures (eg, cryotherapy, electrodessication/curettage, etc) had been available; however, their efficacy and safety have not been rigorously evaluated in well-controlled clinical trials, and they often involve burning, cutting, or freezing z a noninvasive, well-tolerated, topical agent for the removal of sks is an important unmet treatment need z a proprietary, stabilized hydrogen peroxide topical solution, 40% (w/w) (a-101 40) was approved by the fda in december 2017 for sks that are raised2 z two identical double-blind, randomized, phase 3 studies showed that, after 2 treatments per lesion, significantly more patients treated with a-101 40 completely cleared all 4 target sks on the trunk, extremities, and face, whereas no patients treated with vehicle cleared all 4 target sks2 z the main objective of the current study was to evaluate the safety of a-101 40 after completion of up to 4 treatments per lesion of 4 target sks on the trunk, extremities, and face materials and methods patients and study design z multicenter, open-label study (nct02667288) z eligible patients: aged ≥ 18 years with 4 eligible sks on the trunk, extremities, and face, identified by the study investigator z eligible lesions were stable, typical sks, measuring 5-15 mm in length and width, > 0-2 mm in thickness, with a physician lesion assessment (pla)™ grade of ≥ 2 (table 1)2 — target sks could not be located on the eyelid, within 5 mm of the orbital rim, inside the orbital rim, in an intertriginous area, or pedunculated z all sks were treated on day 1; on days 22, 43, and 64, any previously treated sks with a pla score > 0 were retreated z patients were followed for 84 days after the fourth treatment visit (total 148 days) z at day 148, the investigator assessed sks using the validated pla z safety was assessed at all visits, including end of study (day 148) table 1. validated physician lesion assessment (pla)2 scale grade descriptor 0 clear: no visible sk 1 near clear: a visible sk with a surface appearance different from the surrounding skin (not elevated) 2 thin: a visible sk (≤ 1 mm) 3 thick: a visible sk (> 1 mm) safety endpoints z treatment-emergent adverse events (teaes), local skin reactions (lsrs), laboratory evaluations, and vital signs z the safety population comprised all patients who began treatment. the intent-to-treat population comprised all patients who were enrolled results z a total of 147 patients were enrolled and treated, and 139 patients (94.6%) completed the study z the mean age of patients was 68 years (range, 35-94): 41% were aged ≥ 71 years, 68% were women, and 94% were caucasian — fitzpatrick skin types 1 to 6 were represented: • type 1: 12 (8.2%); type 2: 71 (48.3%); type 3: 47 (32.0%);type 4: 11 (7.5%); type 5: 4 (2.7%); type 6: 2 (1.4%) z all patients had at least 1 target sk retreated on days 22, 43, and 64 safety z teaes were reported for 25 (17%) patients, and all were reported as mild or moderate in intensity (table 2) — one patient experienced a treatment-related teae (contact/skin irritation) — no patient discontinued due to a teae or serious adverse event (sae) z lsrs were predominantly mild and most commonly included transient pruritus, stinging, crusting, edema, erythema, and scaling that usually resolved by the next visit — the majority of sks had no lsrs by day 148, and the few reported lsrs were generally mild (table 3; figure 1) table 2. overview of teaes (safety population) (n = 147) number of aes reported 32 patients with teaes, n (%) 25 (17.0) number of saes reported 0 patients with saes, n (%) 0 patients with teaes by severity, n (%) mild 17 (11.6) moderate 8 (5.4) severe 0 patients who discontinued the study due to teaes/saes, n (%) 0 patients with treatment-related teaes, n (%) 1 (0.7) table 3. percent of treated sks with lsrs mild moderate severe no reaction scaling 32% 2% < 1% 66% hyperpigmentation 11% 3% 0% 86% crusting 11% 3% < 1% 86% erythema 8% < 1% 0% 92% hypopigmentation 6% 1% 0% 93% pruritus 1% 0% 0% 99% scarring < 1% < 1% 0% 99% atrophy 0% 0% 0% 100% edema 0% 0% 0% 100% stinging 0% 0% 0% 100% erosion 0% 0% 0% 100% ulceration 0% 0% 0% 100% vesicles/bullae 0% 0% 0% 100% figure 1. patient photos of sks before and after a-101 40 treatment baseline final result (day 148) baseline final result (day 148) references 1. bickers dr, et al. j am acad dermatol. 2006;55:490-500. 2. baumann ls, et al. j am acad dermatol. 2018; epub ahead of print. doi: 10.1016/j. jaad.2018.05.044. acknowledgments this study was funded by aclaris therapeutics, inc. editorial support for this poster was provided by peloton advantage, parsippany, nj, and funded by aclaris therapeutics, inc. disclosures valerie d. callender, ellen h. frankel, jonathan s. weiss, and william p. werschler are investigators for aclaris therapeutics, inc. christopher powala and stuart d. shanler are employees of aclaris therapeutics, inc. brian b. beger and esther estes are former employees of aclaris therapeutics, inc. conclusions 1 up to 4 treatment sessions with hydrogen peroxide topical solution, 40% (w/w) were safe and well tolerated for patients with seborrheic keratoses 2 on december 14, 2017, a-101 40 became the first and only us fdaapproved topical treatment for raised seborrheic keratoses open-label study of a-101, a 40% hydrogen peroxide topical solution, in patients with seborrheic keratosis valerie d. callender, md,1 ellen h. frankel, md,2 jonathan s. weiss, md,3 william p. werschler, md, faad, faacs,4 christopher powala,5 brian b. beger,6 esther estes, md, mph,6 stuart d. shanler, md, faad, facms5 1callender center for clinical research, llc, glenn dale, md; 2clinical partners, llc, johnston, ri; 3gwinnett clinical research center, inc., snellville, ga; 4premier clinical research, spokane, wa; 5aclaris therapeutics, wayne, pa; 6former employee, aclaris therapeutics, wayne, pa presented at the fall clinical dermatology conference, october 18–21, 2018, las vegas, nevada skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 149 rising derm stars® understanding of abbreviations in dermatology: a survey of primary care providers bethany rohr md1, andrea berger mas, jill henley do, nichole hossler md, eric hossler md 1department of dermatology, geisinger health system, danville, pa background/objectives: abbreviations in medical documentation limit effective communication between health care providers. methods: a survey containing 5 demographic questions and 20 fill-in the blank questions was conducted from august through october of 2016. respondents included physicians and mid-level providers in the fields of medicine, medicine-pediatrics, pediatrics and family practice. results: responses were provided by 57 total providers in the departments of family medicine 39 (68.4%), internal medicine 7 (12.3%), medicine/pediatrics 6 (10.5%), and pediatrics 5 (8.8%). on average, providers correctly answered 7.2 (36.2%) of the twenty dermatology abbreviations. the abbreviations with the highest number of correct responses were ak-actinic keratosis (91.2%), bcc-basal cell carcinoma (86.0%), scc-squamous cell carcinoma (86.0%), skseborrheic keratosis (82.5%) and mtxmethotrexate (71.9%), and the lowest were ilkintralesional kenalog (1.8%), aa alopecia areata (1.8%), pdtphotodynamic therapy (1.8%), and mmsmohs micrographic surgery (3.5%). family medicine providers scored better (median of 40% correct) compared to providers from other departments (internal medicine and medicine/pediatrics combined 35%, pediatrics 15%) (p-value = 0.0115). conclusion: niche dermatologic abbreviations are often unrecognized by primary care providers and should be avoided in medical documentation. references: 1. politis j, lau s, yeoh j, brand c, russell d, liew d. overview of shorthand medical glossary (omg) study. intern med j. 2015;45:423-427. 2. patel cb, rashid rm. averting the proliferation of acronymophilia in dermatology: effectively avoiding adcomsubordcomphibspac. j am acad dermatol. 2009;60:340-344. 3. shilo l, shilo g. analysis of abbreviations used by residents in admission notes and discharge summaries. qjm. 2018;111:179-183. 4. sinha s, mcdermott f, srinivas g, houghton pw. use of abbreviations by healthcare professionals: what is the way forward? postgrad med j. 2011;87:450-452. 5. vale sm, koenig k, ailor sk, martin k. knowledge of dermatologic abbreviations: a survey of patients and physicians who are not dermatologists. j am acad dermatol. 2017;76:362-364. powerpoint presentation angela yen moore1,2, stephen moore1,3, luke moore1, stephen k tyring3 1arlington research center, arlington, tx, usa; 2baylor university medical center, dallas, tx, usa 3department of dermatology, the university of texas mcgovern medical school, houston, tx, usa introduction results case report references conclusions • acne vulgaris is a common disease of both males and females, usually manifesting initially during adolescence. • 60-70% of patients present with acne on the trunk. 1 • since severity of truncal acne does not correlate with severity of facial acne, the psychosocial burden and physical pain and bleeding of truncal acne cannot be underestimated. 2 • antibiotics in the tetracycline family have been prescribed as acne treatments for many years. • sarecycline, a narrow-spectrum 3rd generation tetracycline-class antibiotic, was fda approved for moderate-to-severe acne vulgaris in patients 9 years of age and older in october, 2018. • sarecycline exhibits potent anti-inflammatory activity, activity against cutibacterium acnes and clinically relevant gram-positive bacteria, but reduced activity against gram-negative bacteria commonly found in the gut, may contribute to its favorable side effect profile. 3 • significant improvement in truncal acne, using iga assessments, was reported with sarecycline in phase 3 clinical trials. 4,5 • we present a 18-year-old hispanic male with severe acne vulgaris on the trunk treated with sarecycline monotherapy for 3 months, and assessed iga scores and lesion counts of the trunk, with objective photographs, at weeks 3, 6, 9 and 12. • at baseline, the patient presented with severe acne vulgaris on the trunk, with 77 inflammatory lesions on the trunk. • this case report confirms clinical observation of rapid improvement of truncal acne in phase 3 clinical trials. 1. del rosso jq, stein-gold l, lynde c, tanghetti e, alexis af. truncal acne: a neglected entity. j drugs dermatol. 2019;18(12):2051208. 2. tan j, beissert s, cook-bolden f, et al. impact of facial and truncal acne on quality of life: a multi-country population-based survey. jaad international. 2021;3:102-110. doi:10.1016/j.jdin.2021.03.002 3. bunick cg, keri j, tanaka sk, et al. antibacterial mechanisms and efficacy of sarecycline in animal models of infection and inflammation. antibiotics (basel). 2021;10(4):439. doi:10.3390/antibiotics10040439 4. moore a, green lj, bruce s, et al. once-daily oral sarecycline 1.5 mg/kg/day is effective for moderate to severe acne vulgaris: results from two identically designed, phase 3, randomized, double-blind clinical trials. journal of drugs in dermatology : jdd. 2018;17(9):987996. 5. del rosso jq, stein gold l, baldwin h, et al. management of truncal acne with oral sarecycline: pooled results from two phase-3 clinical trials. j drugs dermatol. 2021;20(6):634-640. doi:10.36849/jdd.2021.6204 sarecycline: rapid improvement of truncal acne in hispanic male clinical implications • at weeks 3, 6, 9, and 12, inflammatory lesions counts on the trunk decreased to 13 (83% reduction), 13 (83% reduction), 8 (90% reduction), and 7 (91% reduction), respectively. • iga score for the trunk decreased from iga of 4 at baseline to 1 (almost clear) at week 12. • no side effects of special interest for tetracycline-family antibiotics, including nausea, diarrhea, esophagitis, pseudotumor cerebri, blurry or double vision, dizziness, vertigo, or blue-gray pigmentation, were observed. • oral sarecycline may offer a practical and convenient treatment for truncal acne, especially in areas where topical agents can be difficult to apply. baseline week 3 week 6 week 9 week 12 results figure 2. patient photos of back disclosures: investigator initiated trial funds were received from almirall, llc. https://doi.org/10.1016/j.jdin.2021.03.002 https://doi.org/10.3390/antibiotics10040439 https://doi.org/10.36849/jdd.2021.6204 skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 201 original research online patient health resources in nonmelanoma skin cancer: an assessment of readability, quality, and comprehensiveness terri shih bs1*, allison brimacombe bs, mgh1*, vivian y. shi md2, jennifer l. hsiao md3 1 david geffen school of medicine, university of california los angeles, los angeles, ca 2 department of dermatology, university of arkansas for medical sciences, little rock, ar 3 department of dermatology, university of southern california, los angeles, ca *authors have contributed equally to the work nonmelanoma skin cancer (nmsc) is the most common skin cancer globally1 and affects over 3 million people in the united states annually.2 the incidence of basal cell carcinoma (bcc) and squamous cell carcinoma (scc) has continued to increase over the last decade, especially in elderly populations.3 low health literacy negatively correlates with the ability to evaluate online health information.4 the majority (80%) of internet users search online for health information.5 however, previous studies have found that the readability of online health resources for dermatologic conditions such as melanoma6,7 and atopic dermatitis8 fails to meet the american medical association (ama) recommended readability level of 6th grade. there is a paucity of data on the features and accessibility of patient online health resources on nmsc. here, we investigate the readability, quality, and comprehensiveness of online resources pertaining to nmsc. abstract background: nonmelanoma skin cancer (nmsc), the most prevalent skin cancer, affects over 3 million in the united states annually. although most patients search for health information on the internet, the readability and quality of nmsc online resources is unknown. objective: we examine the readability, quality, and comprehensiveness of content in nmsc websites. methods: top 50 google search results for “nonmelanoma skin cancer”, “basal cell skin cancer”, and “squamous cell skin cancer” were evaluated. advertisements, blogs, scientific articles, and noncomprehensive, professional, and irrelevant sites were excluded. six readability scales assessed readability. jama benchmark and discern instrument assessed quality. content was evaluated for comprehensiveness. pearson’s correlation examined the relationship between readability and quality. results: seventy-nine websites met inclusion criteria. average readability level was 11th grade (range 6.8-17.9). no websites met the full criteria of jama benchmark. only 16.4% had “good”/“excellent” quality per discern instrument. quality and readability scores were not correlated. most websites discussed risk factors (87.3%), prevention (73.4%), and surgical (87.3%) and nonsurgical (82.3%) treatments. 50.6% included skin cancer images, of which only 17.5% were of skin of color patients. conclusion: online nmsc resources need improved readability, quality, and diversity in their representation of skin types. introduction skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 202 a search was conducted using the google search engine on june 10th, 2021 using three independent search terms: “nonmelanoma skin cancer”, “basal cell skin cancer”, and “squamous cell skin cancer”. browser search history and cookies were cleared, and the searches were performed in incognito mode to avoid influence by personal user data. the first 50 results for each term were evaluated. websites that were advertisements, blog posts, intended for healthcare professionals, scientific articles, non-comprehensive, or irrelevant to the studied topics of nmsc, bcc, or scc were excluded. a preferred reporting items for systematic reviews and meta-analysis (prisma) diagram outlining the search schema is shown in figure 1. readability was assessed using six established and validated readability scales (flesch reading ease, flesch-kincaid grade level, gunning-fog index, smog index, coleman-liau index, automated readability index) which measure variables such as sentence length and syllables per word. quality was assessed with the jama benchmark and discern instruments. jama benchmark assesses 4 criteria: authorship, attribution (i.e. references), disclosure (i.e. mention of conflicts of interest), and currency (i.e. whether the resource is dated). the modified discern instrument (15 items)9 analyzes overall reliability and quality of written health information. discern scores were independently assessed by two reviewers (ab and ts); discrepancies within two points or fewer were averaged, and any other discrepancies were discussed to consensus with a third independent reviewer (jlh). data were also collected on author source (i.e. author degree, whether author is a dermatologist), date of most recent website modification, and if websites included discussion of: nmsc risk factors, preventative care, nonsurgical treatments, and surgical treatments. as another gauge of website comprehensiveness, inclusion of multimedia resources besides text, such as videos and images, was measured. the inclusion of skin of color (soc) images was also evaluated. correlation between quality and readability was assessed using pearson’s correlation. p-values < 0.05 were considered statistically significant. all analyses were completed in r v4.1.0. nonmelanoma skin cancer (nmsc) a total of 50 websites were reviewed for the search term “nonmelanoma skin cancer”, and 24 of these met inclusion criteria (supplemental table 1). the top 5 readable websites are shown in table 1. the average grade level was 11.0 (11th grade) and ranged from 7.5 to 16.3. the websites with the most difficult readability were mayo clinic (16.3), texas oncology (13.7), and moffitt (13.6). none of the websites met the recommended 6th grade reading level per the ama. the average jama benchmark score was 1.6 out of 4, with no websites achieving the full 4 points. references were disclosed in 66.7% of websites (16/24), conflicts of interest readily visible in 16.7% (4/24), and date of publication or review was noted in 54.2% (13/24). author name was provided methods results skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 203 figure 1. schematic of search strategy and evaluation of top searched online health resources for nonmelanoma skin cancer skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 204 table 1. top 5 websites in readability and in quality for nonmelanoma skin cancer, basal cell skin cancer, and squamous cell skin cancer skin condition top 5 websites in readability (average readability grade level)^ top 5 websites in quality* (modified discern score / jama benchmark scores) nonmelanoma skin cancer florida cancer (7.5) cancer.org (68.5 / 2) hopkins medicine (7.7) cancer.net (65 / 3) cedars sinai (8.2) cancer.gov (56 / 3) skin cancer (8.8) university of michigan health (56 / 3) university of michigan health (9.3) web md (50 / 3) basal cell skin cancer webmd (6.8) cancer research uk (69 / 3) hopkins medicine (7.7) cancer.org (68.5 / 2) cancer research uk (8.9) cancer.net (64.5 / 3) mount sinai (9.1) mount sinai (50 / 3) center for disease control and prevention (9.2) dana farber (49 / 2) squamous cell skin cancer medline plus (8.2) cancer research uk (69 / 3) mount sinai (8.2) cancer.org (68.5 / 2) cancer research uk (8.9) cancer.net (64.5 / 3) american osteopathic college of dermatology (9.1) cancer.gov (56 / 3) center for disease control and prevention (9.2) very well health (52.5 / 3) ^average readability grade level is the average of flesch kincaid grade level, gunning fog score, smog index, coleman-liau index, and automated readability index scores. *websites listed based on modified discern scores. the modified discern instrument has a maximum score of 75. the jama benchmark has a maximum score is 4. on 20.8% (5/25) websites, of which 100% (5/5) were dermatologists with an md degree. the average discern score was 40.8, characterized as “fair,” ranging from 17.5 to 68.6; 11 websites (45.8%) were “poor” or “very poor.” the highest quality websites based on the discern instrument were cancer.org (68.5), cancer.net (65), cancer.gov (56), and university of michigan health (56), for which readability levels were 11.1, 10.4, 10.1, and 9.3 respectively. in assessing comprehensiveness, 79.2% of websites (19/24) mentioned risk factors, 62.5% (15/24) mentioned preventative care, 75.0% (18/24) discussed nonsurgical treatments, and 75.0% (18/24) discussed surgical treatments. over half (62.5%) of the websites included multimedia resources, of which 20.8% (5/24) included video, and 58.3% (14/24) included images. only 37.5% (9/24) websites included images of skin cancer, of which only 2 of the 9 (22.2%) included images of skin cancer in soc patients. 45.8% (11/24) of websites were available in at least one other language. there was no significant correlation between discern quality score and average readability score) (r2=0.017, p=0.54). basal cell carcinoma (bcc) a total of 50 websites were reviewed for the search term “basal cell skin cancer”, and 27 skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 205 of these met inclusion criteria (supplemental table 2). the average grade level was 11.0 (11th grade) and ranged from 6.8 to 17.9. the websites with the most difficult readability were dermnet nz (17.9), wikipedia (14.7), and city of hope (14.7). there were no websites that met the ama recommended 6th grade reading level. the average jama benchmark score was 1.6 out of 4, with no websites achieving 4/4 points. references were disclosed on 48.1% (13/27) of websites, conflicts of interest were readily visible on 22.2% (6/27) of websites, and date of publication or review was noted on 59.3% (16/27) of websites. author name was provided on 25.9% (7/24) of websites, of which 85.7% (6/7) were dermatologists with an md degree. the average discern score was 40.5, characterized as fair, ranging from 16.0 to 69.0; 12 websites (44.4%) were “poor” or “very poor.” the highest quality websites based on the discern instrument were cancer research uk (69), cancer.org (68.5), and cancer.net (64.5), for which readability levels were 8.9, 11.1, and 10.4 respectively. in assessing content, 85.2% (23/27) of websites mentioned risk factors, 81.5% (22/27) mentioned preventative care, 81.5% (22/27) discussed nonsurgical treatments, and 88.9% (24/27) discussed surgical treatments. most websites (92.6%) included multimedia, of which 44.4% (12/27) included video, and 81.5% (22/27) included images. only 55.6% (15/27) of websites included images of skin cancer, of which only 1 of the 15 (6.7%) included images of skin cancer in soc patients. 40.7% (11/27) of websites were available in at least one other language. there was no correlation between quality (discern score) and average readability score (r2=0.002, p=0.84). squamous cell carcinoma (scc) a total of 50 websites were reviewed for the search term “squamous cell skin cancer”, and 28 of these met inclusion criteria (supplemental table 3). the average grade level was 11.2 (11th grade) and ranged from 8.2 to 15.5. the websites with the most difficult readability were dermnet nz (15.5), merck manuals (13.6), and webmd (13.5). there were no websites that met the recommended 6th grade reading level per the ama. the average jama benchmark score was 1.8 out of 4, with no websites achieving the full 4 points. references were provided in 53.6% (15/28) of websites, conflicts of interest were readily visible on 25.0% (7/28) of websites, and date of publication or review was noted on 64.3% (18/28) of websites. author name was provided on 32.1% (9/28) of websites, of which 77.8% (7/9) were dermatologists with an md degree. the average discern score was 40.9, characterized as fair, ranging from 23.0 to 69.0; half of the websites (14/28) were “poor” or “very poor.” the highest quality websites based on the discern instrument were cancer research uk (69), cancer.org (68.5), and cancer.net (64.5), for which readability levels were 8.9, 11.1, and 10.4 respectively. in assessing content, 96.4% (27/28) of websites mentioned risk factors, 75.0% (21/28) mentioned preventative care, 89.3% (25/28) discussed nonsurgical treatments, and 96.4% (27/28) discussed surgical treatments. most websites (78.6%) included multimedia, of which 21.4% (6/28) included video, and 75.0% (21/28) included images. only 57.1% (16/28) of websites included images of skin cancer, of which 4 out of the 16 (25.0%) included images of skin cancer in soc patients. 35.7% (10/28) of websites were available in at least one other skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 206 language. there was no correlation between quality (discern score) and readability (average readability score) (r2=0.079, p=0.15). overall, out of the total 79 nmsc, bcc and scc websites that were examined, the majority of websites discussed risk factors (87.3%), preventative care (73.4%), nonsurgical (82.3%) and surgical treatment options (87.3%) and included multimedia resources (78.5%) (figure 2). images of skin cancer were used in half (40/79, 50.6%) of the websites, and of those, less than a fifth (7/40, 17.5%) included images in patients. online health resources for nmsc, bcc, and scc fail to meet recommended reading levels and are highly variable in quality and comprehensiveness. none of the websites in this analysis met the ama recommended 6th grade reading level for patients, with an average readability level of 11th grade found across all websites analyzed. in terms of quality assessment, no websites met all 4 criteria on the jama benchmark, and fewer than a fifth of the websites were characterized as “good” or “excellent” per the discern instrument. only 21/79 (26.5%) websites listed authorship. there was no correlation between quality and readability amongst the websites, highlighting an opportunity to improve readability without compromising the quality of content in written online health materials. across websites, the least discussed topic was nmsc preventative care. over a quarter (26.5%) of websites did not include this topic, therefore limiting patient education in primary prevention strategies. results of this study are consistent with previously published readability studies for melanoma. two studies on melanoma reported similar inaccessibility in readability and high variation in quality of content.6,7 additionally, a prior readability study of online content from a search of the term “skin cancer” reported 90% of sites to have an unacceptable readability score on at least one assessment.10 our study highlights the wide range in quality, readability, and comprehensiveness when specifically evaluating nmsc websites. low health literacy is directly correlated with poorer health outcomes, including an increase in hospitalizations and decrease in preventative screenings.11 in the united states, it is estimated that 89 million people have limited health literacy,12 highlighting the urgent need to improve the readability of nmsc online health content. incorporation of multimedia has been reported to be a valuable tool in optimizing discussion skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 207 figure 2. comprehensiveness of nonmelanoma skin cancer, basal cell carcinoma, and squamous cell carcinoma websites patient education.13 exposure to skin cancer images may improve patient self-exams and earlier detection.14 however, only half of the websites we analyzed included images of skin cancer, representing a missed opportunity for patient education. although the incidence of nmsc is lower in patients of soc patients compared to white patients, soc patients have been found to have disproportionately poor outcomes from nmsc, often presenting with later stage or more aggressive cancers. 15 despite this, images of skin cancer in soc patients were only present in 8.9% of websites analyzed in this study. our findings support a prior study that analyzed the top google image search results of 71 skin conditions, and found that out of 3700 photographs, less than 10% represented darker skin tones.16 larger scale studies are needed to address questions regarding the disparities in skin cancer outcomes in ethnic minority groups.17 online health resources can take a step towards closing this gap by increasing the representation of soc patients in skin cancer images. although google is the top utilized search engine globally,18 one limitation of this study is the utilization of a single search engine. even though only the top 50 search results were evaluated, this likely represents the websites that are utilized most often by patients, as the first page of search results has been shown to capture 71-92% of all search traffic clicks.19 skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 208 although a majority of online health resources for nmsc are comprehensive in content, readability and quality of the websites vary widely and are generally suboptimal. additionally, online images of nmsc in soc patients are severely underrepresented. this study highlights the need for improved readability and quality of online nmsc resources. as the use of online health resources becomes increasingly popular, it is crucial for dermatologists to vet online dermatologic resources for patients, and to prioritize readability, accessibility, and representation of diverse skin types when creating online content. conflict of interest disclosures: jlh is on the board of directors for the hidradenitis suppurativa foundation, has served as a consultant for boehringer ingelheim, novartis, and ucb, and has served as a consultant and speaker for abbvie. vys is on the board of directors for the hidradenitis suppurativa foundation (hsf), is a stock shareholder of learn health and has served as an advisory board member, investigator, speaker, and/or received research funding from sanofi genzyme, regeneron, abbvie, eli lilly, novartis, sun pharma, leo pharma, pfizer, incyte, boehringer-ingelheim, aristea therapeutics, menlo therapeutics, dermira, burt’s bees, galderma, kiniksa, ucb, webmd, target-pharmasolutions, altus lab, myor, polyfin, gpskin and skin actives scientific. there was no financial transaction for the preparation of this manuscript. all other authors report no conflicts of interest. funding: this study was funded by a short term training program (sttp) grant supported by the david geffen school of medicine at ucla (allison brimacombe) corresponding author: jennifer l. hsiao, md 1441 eastlake ave ezralow tower, suite 5301 phone: (310) 601-3367 email: j.hsiao.publications@gmail.com references: 1. bray f, ferlay j, soerjomataram i, et al. global cancer statistics 2018: globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries. ca cancer j clin. 2018;68(6):394–424. 2. rogers hw, weinstock ma, feldman sr, et al. incidence estimate of nonmelanoma skin cancer (keratinocyte carcinomas) in the u.s. population, 2012. jama dermatol. 2015 oct;151(10):1081–6. 3. ciążyńska m, kamińska-winciorek g, lange d, et al. the incidence and clinical analysis of nonmelanoma skin cancer. sci rep. 2021 feb 22;11(1):4337. 4. diviani n, van den putte b, giani s, et al. low health literacy and evaluation of online health information: a systematic review of the literature. j med internet res. 2015 may 7;17(5):e112. 5. fox s. the social life of health information, 2011 [internet]. pew research center’s internet & american life project; 2011. available from: http://pewinternet.org/reports/2011/social‐life‐ of‐health‐info.aspx 6. ibrahim ams, vargas cr, koolen pgl, et al. readability of online patient resources for melanoma. melanoma res. 2016 feb;26(1):58– 65. 7. alshaikh ea, almedimigh af, alruwaili am, et al. patient-focused online resources for melanoma: highly variable content and quality. j cancer educ. 2019 aug 1;34(4):775–781. 8. modiri o, yee d, shi vy, et al. readability, quality, and timeliness of online health resources for atopic dermatitis. dermat contact atopic occup drug. 2020 dec 1; 9. weil ag, bojanowski mw, jamart j, et al. evaluation of the quality of information on the internet available to patients undergoing cervical spine surgery. world neurosurg. 2014 aug;82(1–2):e31-39. 10. basch ch, fera j, ethan d, et al. readability of online material related to skin cancer. public health. 2018 oct 1;163:137–140. 11. weiss bd. health literacy and patient safety: help patients understand. manual for clinicians. 2nd ed. [internet]. [cited 2021 jul 27]. available from: https://psnet.ahrq.gov/issue/health-literacy-andpatient-safety-help-patients-understand-manualclinicians-2nd-ed 12. kutner m, greenberg e, jin y, et al. the health literacy of america’s adults: results from the 2003 national assessment of adult literacy [internet]. national center for education conclusion mailto:j.hsiao.publications@gmail.com skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 209 statistics; 2006 [cited 2021 jul 27]. available from: https://nces.ed.gov/pubsearch/pubsinfo.asp?pu bid=2006483 13. delcambre m, haynes d, hajar t, et al. using a multimedia tool for informed consent in mohs surgery: a randomized trial measuring effects on patient anxiety, knowledge, and satisfaction. dermatol surg off publ am soc dermatol surg al. 2020 may;46(5):591–8. 14. mcwhirter je, hoffman-goetz l. visual images for patient skin self-examination and melanoma detection: a systematic review of published studies. j am acad dermatol. 2013 jul;69(1):47–55. 15. davis ds, robinson c, callender vd. skin cancer in women of color: epidemiology, pathogenesis and clinical manifestations. int j womens dermatol. 2021 mar;7(2):127–134. 16. kurtti a, austin e, jagdeo j. representation of skin color in dermatology-related google image searches. j am acad dermatol. 2021 mar 17;s0190-9622(21)00582-x. 17. hogue l, harvey vm. basal cell carcinoma, squamous cell carcinoma, and cutaneous melanoma in skin of color patients. dermatol clin. 2019 oct;37(4):519–26. 18. search engine market share worldwide [internet]. statista. [cited 2021 aug 6]. available from: https://www.statista.com/statistics/216573/world wide-market-share-of-search-engines/ 19. shelton k. council post: the value of search results rankings [internet]. forbes. [cited 2021 aug 4]. available from: https://www.forbes.com/sites/forbesagencycoun cil/2017/10/30/the-value-of-search-resultsrankings/ skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 366 compelling comments storytelling in dermatology robert t. brodell, md1, david w. brodell, md2 1professor and chair, department of dermatology, professor and interim chair, department of pathology, university of mississippi medical center, jackson, mississippi 2department of dermatology, university of rochester school of medicine, rochester, new york at a recent conference, john d. trybus, phd, a social strategist from the georgetown university center for social impact communication, promoted storytelling as a way to influence legislators for the benefit of physicians and their patients. in fact, there is evidence that politicians and voters are more likely to be swayed by an emotional story than by scientific facts. 1, 2, 3 effective stories help us make sense of complexity. 4, 5 a brief case emphasizes the importance of social strategy to motivate patients and promote treatment adherence. report of a case: a 17 year-old male with severe nodulocystic acne presented with his mom after failing to improve on a variety of topicals and systemic antibiotics. oral 13-cis retinoic acid was recommended. benefits and risks were discussed including the one in a thousand risk of developing depression, and vanishingly rare risk of colitis that is identical to the risk using oral antibiotics. the mother listened intently to my scientific arguments, but refused to let her son take the medication. the dermatologist then told a story about his five children, three of whom had taken 13-cis retinoic acid for their severe acne. the physician dryly noted that he did not like his children, paused…and, then admitted to loving his children. each child had cleared rapidly and remained clear, and none experienced any significant side effects beyond predictable dryness. the patient’s mother felt emotionally persuaded, and her son began a trial of 13 cis retinoic acid clearing completely in 5 months. what are the components of a good story?6 first, it must be short and have a finely honed plot sometimes referred to as trajectory.6 in fact, a patient’s attention span is often less than 10 seconds.7,8,9 second, storytelling must be strategic.6, 10 our story was designed to motivate a mother who loves her children, just like the dermatologist. thirdly, the story was perfectly honest, authentic, and personal.11 it would be ethically inexcusable to lie to a patient. fourthly, good stories are relatable. in our case, humor was used to engage the patient with a strong emotionlove for their children!1 fifth, there was a call to action with a “hook” that was immediately persuasive. 1, 12,13 a physician gave the same medication to the children he loves! finally, the effectiveness of the story is measurable. in this case the patient and his skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 367 mother accepted the recommended medication. if a story repeatedly fails to achieve the desired outcome, it is time to develop an alternate approach! in fact, stories do not always work because they are subject to interpretation. it is worthwhile to ask an open-ended question that might explain why the desired action was not achieved. the physician might ask: did i offend you with my failed attempt at humor? they might just blurt out an explanation. in addition, the mother and son have their own stories that may relate to side effect experienced by a friend. physicians must be good listeners as well as storytellers to identify the issues that could explain the family’s fears. it may be an effective strategy to highlight the similarities between the physician and patient stories or adopt the patient’s story with a twist. in summary, dermatologists should never minimize the importance of a good story and continue to motivate their patients with timetested tales. skillful storytelling in the context of evidence may serve to maximize adherence. though story telling in american politics is sometimes based on half-truths and deception, dermatologic anecdotes must be grounded in fact. conflict of interest disclosures: robert t. brodell, m.d., discloses the following potential conflicts of interest: advisory board: novartis. clinical trials have been performed for genentech, novartis, and janssen biotech, inc. david brodell has no conflicts of interest to disclose. funding: none corresponding author: robert t. brodell, m.d. professor and chair, department of dermatology professor of pathology university of mississippi medical center instructor in dermatology university of rochester school of medicine and dentistry 601-815-8000 rbrodell@umc.edu references: 1. berger j. contagious: why things catch on. new york, ny. simon and schuster; 2009. 2. cron l. wired for story: the writer's guide to using brain science to hook readers from the very first sentence. emeryville, ca ten speed press; 2012. 3. rodriguez f, re rhodes, kf miller & p shah. examining the influence of anecdotal stories and the interplay of individual differences on reasoning thinking & reasoning . 2016; 22(3); 274-296. 4. mckee r. story: substance, structure, style and principles of screenwriting. it books; 1997. 5. gottshall j. stories change minds and key to their effectiveness: the story telling animal. life sciences; 2013. 6. stories worth telling: a guide to strategic and sustainable nonprofit storytelling. georgetown university center for social impact communication. meyer foundation. meyerfoundation.org 1-62. 7. cornish d, d dukette. the essential 20: twenty components of an excellent health care team. pittsburgh pa: rosedog books, 2009: 72-73. 8. mcspadden k. you now have a sorter attention span than a goldfish. time. may 14, 2015. 9. ruff ha kr lawson. development of sustained, focused attention in young children during free play. developmental psychology. 1990. 26(1):85-93. 10. horsey, d. tell your story...well & truly. monthly developments magazine, 2012. 30(4), 810. 11. storytelling: the five building blocks your stories need. center for social impact communication, georgetown university 2014. (www.gcn.org/articles/effective-storytelling-thefive-building) 12. mccabe a, c peterson. good story emotional leads to motive for action. what makes a good story. journal of psycholinguistic research. 1984; 13(6): 457. 13. heath, c. & heath, d. made to stick: why some ideas survive and others die. new york, ny: random house. 2007 mailto:rbrodell@umc.edu http://www.tandfonline.com/author/rodriguez%2c+fernando http://www.tandfonline.com/author/rhodes%2c+rebecca+e http://www.tandfonline.com/author/miller%2c+kevin+f http://www.tandfonline.com/author/shah%2c+priti http://www.tandfonline.com/toc/ptar20/current http://www.gcn.org/articles/effective-storytelling-the-five-building http://www.gcn.org/articles/effective-storytelling-the-five-building skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 316 short communication multifaceted facial tumor posing a therapeutic challenge brittany urso, md1, vivian laquer, md1, joseph hillman, md2, christopher zachary, mbbs frcp1, janellen smith, md1 1department of dermatology, university of california irvine, irvine, ca 2st. joseph mission hospital, mission viejo, ca nevus sebaceous (ns) are benign congenital hamartomas which primarily affect the head and neck. most lesions occur sporadically without any familial predisposition; however, ns can be associated with schimmelpenning syndrome or phakomatosis pigmentokeratotica. at birth, they present as a thin alopecic plaque, but post-pubertally they thicken and become verrucous due to hormonal influences. in late adulthood, secondary appendageal benign and malignant neoplasms, such as trichoblastoma (tbl), syringocystadenoma papilliferum (spap), and basal cell carcinoma (bcc), may arise.1 while ns are associated with multiple neoplasms, especially when located on the scalp, they rarely present simultaneously within the same lesion on the face.1,2 herein, we report an unusual presentation of a ns with numerous concomitant neoplasms. a 58-year-old vietnamese male presented to clinic for evaluation of a birthmark on his left cheek which has been enlarging over a two-month period. he also reported intermittent bleeding pink and black bumps within the birthmark. physical exam revealed a 5x8 cm verrucous plaque studded with pink to brown nodules on the left preauricular cheek, extending into the lateral hair line (figure 1a). no lymphadenopathy was noted. scouting biopsies revealed noduloinfiltrative bcc and mri showed no evidence of deep invasion of the tumor or lymphadenopathy. due to cultural attitudes, he declined surgery under any type of sedation or general anesthesia, but eventually opted for mohs micrographic surgery. complete excision revealed the additional presence of tbl, spap, bcc, and a trichoblastic carcinoma (figure 2). the surgical defect could not be closed primarily so it was partially closed leaving the rest to heal by secondary intention. the scar was later revised with intralesional steroids and laser therapy (figure 1b). our case is interesting due to the patient’s ethnicity, the presence of multiple and unusual tumors, and the large size of the lesion. though skin cancers may develop within a ns, among certain populations, it is rare. a recent review of the taiwanese population showed that malignant conversion in ns is uncommon at about 0.9%, and usually involves bcc.3 in the general population, bcc is the most common malignancy in ns, with an incidence of 1%4 only once has a trichoblastic carcinoma been reported arising in a ns.5 surgical intervention was curative for this patient but involved a large surgical defect that required a thoughtful skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 317 figure 1. (a) clinical image showing a large verrucous plaque studded with pink and pigmented nodules involving the majority of the left face. (b) clinical image of well-healed surgical scar. figure 2. nevus sebaceous with trichoblastic carcinoma. microscopic image showing a large tumor composed of atypical pleomorphic basaloid epithelial cells with follicular differentiation and peripheral palisading. approach for ethnic, psychological, and practical reasons. coming from a rural society in vietnam where the need for general anesthesia is tantamount to a death sentence, this patient was reluctant. fortunately, dermatologic surgeons routinely remove large tumors under local anesthesia and large defects can be repaired using many techniques including a combined closure as in this case. we hope this case emphasizes the importance of cultural sensitivity in patient care, highlights the various tumors associated with ns, and encourages providers to biopsy ns readily for early skin cancer detection. conflict of interest disclosures: none funding: none corresponding author: brittany urso, md department of dermatology university of california irvine 118 med surg i, irvine, ca 92697 phone: 949-824-5515 fax: 949-824-7454 e-mail: burso@hs.uci.edu skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 318 references: 1. namiki t, miura k, ueno m, et al. four different tumors arising in a nevus sebaceous. case rep dermatol. 2016;8(1):75-79. (pmid 27194974) 2. cribier b, scrivener y, grosshans e. tumors arising in nevus sebaceous: a study of 596 cases. j am acad dermatol. 2000 feb; 42 (2 pt 1):263-8. (pmid 10642683) 3. hsu mc, liau jy, hong jl, et al. secondary neoplasms arising from nevus sebaceus: a retrospective study of 450 cases in taiwan. j dermatol. 2016;43(2):175-180. (pmid 26361884) 4. watson it, decrescenzo a, paek sy. basal cell carcinoma within nevus sebaceous of the trunk. baylor university medical center proceedings. 2019; 32(3): 392-393. (pmid 31384196) 5. kim j, lee s, cho p, et al. trichoblastic carcinoma arising from a nevus sebaceous. arch plast surg. 2016;43(3):297299. (pmid 27218034) synopsis sf-36 is a widely used, general questionnaire to assess hrqol across 8 mental and physical domains.4 scores in each domain range from 0–100 and were derived to have a mean score of 50 in the us general population.4 increased scores represent an improvement in hrqol. conclusions improvements across all sf-36 domains were observed from week 8 of czp treatment, and were generally durable through week 144. the greatest improvements were for bodily pain and social functioning, which were the most affected at baseline. these data complement the three-year dlqi results previously reported.1 objectives to assess health-related quality of life over 144 weeks using data from two certolizumab pegol phase 3 trials in moderate to severe plaque psoriasis with the 36-item short form survey data. background • the fc-free, pegylated anti-tumor necrosis factor (tnf) agent certolizumab pegol (czp) has shown durable clinical improvements, and a safety profile consistent with the anti-tnf class, over 144 weeks of treatment in patients with moderate to severe plaque psoriasis (pso).1,2 • pso can negatively impact health-related quality of life (hrqol), with links to pain and discomfort, social stigmatisation, and psychological distress.3 therefore, it is important to understand whether clinical responses translate into long-term improvements in hrqol. • durable improvements in hrqol have been reported over 144 weeks of czp treatment using the dermatology life quality index (dlqi).1 • to complement these positive dlqi results, we report results from the 36-item short form survey (sf-36).4 methods • data were pooled from the cimpasi-1 (nct02326298) and cimpasi-2 (nct02326272) phase 3 trials (figure 1).1 • we report mean change from baseline across all sf-36 domains: – for all patients randomized to czp (combined 200 mg and 400 mg every two weeks [q2w]) through weeks 0–144. – at week 48 separately for patients randomized to czp 200 mg or czp 400 mg q2w. • all data are observed case (oc). results patient population • baseline demographics (table 1) and sf-36 values (table 2) were balanced across treatment groups. all czp-randomized patients to three years • increases in sf-36 domain scores were rapid for patients receiving czp, with improvements apparent from week 8 (figure 2a and figure 2b). • improvements at week 16 were greater for czp-treated patients compared with placebo across all domains, and were durable to week 144 (figure 2a and figure 2b). czp dose comparison after one year • at week 48, greater improvements in all mental sf-36 domains were observed among patients randomized to czp 400 mg q2w compared with czp 200 mg q2w (figure 3). • improvements were also observed across physical domains at week 48, although differences between the two dose groups were smaller (figure 3). d. thaçi,1 a. blauvelt,2 k. reich,3 r.b. warren,4 v. piguet,5,6 f. brock,7 f. fierens,8 v. ciaravino,9 m. lebwohl10 bsa: body surface area; czp: certolizumab pegol; dlqi: dermatology life quality index; oc: observed case; pasi: psoriasis area and severity index; pasi 50/75: ≥50/75% improvement from baseline in pasi; q2w: every two weeks; pga: physician’s global assessment; pso: plaque psoriasis; sd: standard deviation; sf-36: 36-item short form survey; tnf: tumor necrosis factor. figure 1 cimpasi-1 and cimpasi-2 study design institutions: 1institute and comprehensive center for inflammation medicine, university hospital of lübeck, lübeck, germany; 2oregon medical research center, portland, oregon, usa; 3center for translational research in inflammatory skin diseases, institute for health services research in dermatology and nursing, university medical center hamburg-eppendorf and skinflammation® center, hamburg, germany; 4dermatology centre, salford royal nhs foundation trust, manchester nihr biomedical research centre, the university of manchester, manchester, uk; 5division of dermatology, department of medicine, university of toronto, toronto, on, canada; 6division of dermatology, department of medicine, women’s college hospital, toronto, ontario, canada; 7ucb pharma, slough, uk; 8ucb pharma, brussels, belgium; 9ucb pharma, colombes, france; 10icahn school of medicine at mount sinai, new york, new york, usa long-term improvements in health-related quality of life of patients with moderate to severe plaque psoriasis treated with certolizumab pegol: results from the cimpasi-1 and cimpasi-2 phase 3 trials presented at winter clinical 2021 virtual congress | january 16–24 references: 1gordon k. br j dermatol 2020; doi.org/10.1111/bjd.19393; 2blauvelt a. br j dermatol 2020; doi.org/10.1111/bjd. 19314; 3bhosle mj. health qual life outcomes 2006;4:35; 4optum. sf-36v2 health survey. available at www.optum.com/solutions/life-sciences/answer-research/patient-insights/sf-health-surveys/sf-36v2-health-survey [accessed 25th march 2020]. author contributions: substantial contributions to study conception/design, or acquisition/analysis/interpretation of data: dt, ab, kr, rbw, vp, fb, ff, vc, ml; drafting of the publication, or revising it critically for important intellectual content: dt, ab, kr, rbw, vp, fb, ff, vc, ml; final approval of the publication: dt, ab, kr, rbw, vp, fb, ff, vc, ml. author disclosures: dt: honoraria for participation on advisory boards, as a speaker and for consultancy from abbvie, almirall, amgen, biogen, boehringer ingelheim, bristol myers squibb, celgene, ds biopharma, eli lilly, galapagos, janssen, leo pharma, morphosis, novartis, pfizer, regeneron, samsung, sandoz, sanofi genzyme, and ucb pharma; research grants received from celgene, leo pharma, and novartis. ab: scientific adviser and/or clinical study investigator for abbvie, almirall, arena, athenex, boehringer ingelheim, bristol myers squibb, dermavant, eli lilly, forte, galderma, incyte, janssen, leo pharma, novartis, pfizer, rapt, regeneron, sanofi genzyme, sun pharma, and ucb pharma; paid speaker for abbvie. kr: served as advisor and/or paid speaker for and/or participated in clinical trials sponsored by abbvie, affibody, almirall, amgen, avillion, biogen, boehringer ingelheim, bristol myers squibb, celgene, centocor, covagen, dermira, eli lilly, forward pharma, fresenius medical care, galapagos, gsk, janssen, kyowa kirin, leo pharma, medac, msd, miltenyi biotec, novartis, ocean pharma, pfizer, regeneron, samsung bioepis, sanofi, sun pharma, takeda, ucb pharma, valeant/bausch health, and xenoport. rbw: consulting fees from abbvie, almirall, amgen, arena, avillion, boehringer ingelheim, bristol myers squibb, celgene, eli lilly, janssen, leo pharma, novartis, pfizer, sanofi, and ucb pharma; research grants from abbvie, almirall, amgen, celgene, eli lilly, janssen, leo pharma, novartis, pfizer, and ucb pharma. fb, ff, vc: employees of ucb pharma. ml: employee of mount sinai which receives research funds from abbvie, amgen, arcutis, boehringer ingelheim, dermavant, eli lilly, incyte, janssen, leo pharma, ortho dermatologics, pfizer, and ucb pharma; consultant for aditum bio, allergan, almirall, arcutis, avotres, birchbiomed, bmd skincare, boehringer ingelheim, bristol myers squibb, cara therapeutics, castle biosciences, corrona, dermavant, evelo, facilitate international dermatologic education, foundation for research and education in dermatology, inozyme pharma, leo pharma, meiji seika pharma, menlo, mitsubishi pharma, neuroderm, pfizer, promius/dr. reddy’s laboratories, serono, theravance, and verrica. acknowledgements: this study was funded by ucb pharma. we thank the patients and their caregivers in addition to the investigators and their teams who contributed to this study. the authors acknowledge mylene serna, pharmd, ucb pharma, smyrna, ga, usa and susanne wiegratz, msc, ucb pharma, monheim am rhein, germany for publication coordination, ruth moulson, mph, costello medical, london, uk and joe dixon, phd, costello medical, cambridge, uk for medical writing and editorial assistance, and the costello medical design team for design support. all costs associated with development of this poster were funded by ucb pharma. previously presented at eadv 2020 virtual congress | october 29–31 table 1 demographics and baseline characteristics adose adjustments were mandatory or at the investigator’s discretion, based on pasi response; bloading dose of czp 400 mg q2w at weeks 0, 2, and 4 or weeks 16, 18, and 20. adults with pso ≥6 months (pasi >12, bsa affected ≥10% and pga ≥3 on a 5-point scale) were enrolled. at week 48 patients entering the open-label period from blinded treatment received czp 200 mg q2w, with subsequent dose adjustments permitted. patients not achieving pasi 50 at week 16 entered the escape arm for treatment with czp 400 mg q2w; at week 48 these patients continued to receive czp 400 mg q2w or, if they achieved pasi 75, could have had their dose reduced at the investigator’s discretion. figure 2 mean change from baseline in sf-36 domain scores (oc) a) mental domains table 2 baseline sf-36 scores across all domains (oc) aczp 200 mg q2w patients received czp 400 mg q2w at weeks 0, 2, and 4. b) physical domains c) patient numbers with available sf-36 data the all czp group includes all patients initially randomized to czp 200 mg q2w or czp 400 mg q2w. patient numbers reflect those for whom sf-36 data were available at both baseline and the timepoint in question, from which change from baseline could be calculated. placebo data are not shown past week 16. figure 3 mean change from baseline in sf-36 domain scores at week 48 by dose (oc) data are shown as observed for patients randomized to either czp 200 mg or 400 mg q2w, including those that entered the open-label czp 400 mg q2w escape arm at week 16. patient numbers reflect those for whom data were available at both baseline and week 48, from which change from baseline could be calculated. mean ± sd unless stated czp 200 mg q2w (n=186)a czp 400 mg q2w (n=175) all czp (n=361) placebo (n=100) demographics age, years 45.6 ± 13.2 45.0 ± 12.9 45.3 ± 13.0 45.7 ± 13.8 male, n (%) 125 (67.2) 103 (58.9) 228 (63.2) 61 (61.0) bmi, kg/m2 32.0 ± 7.8 31.2 ± 7.9 31.6 ± 7.8 31.2 ± 7.4 baseline characteristics disease duration, years 17.7 ± 12.9 18.5 ± 12.6 18.1 ± 12.7 16.9 ± 12.6 pasi 19.2 ± 7.2 19.6 ± 7.3 19.4 ± 7.3 18.6 ± 6.6 dlqi 14.3 ± 7.4 13.7 ± 6.9 14.0 ± 7.1 13.4 ± 7.8 bsa (%) affected 23.5 ± 14.9 23.6 ± 14.3 23.5 ± 14.6 23.1 ± 13.6 pga, n (%) 3: moderate 128 (68.8) 126 (72.0) 254 (70.4) 72 (72.0) 4: severe 58 (31.2) 49 (28.0) 107 (29.6) 28 (28.0) prior anti-tnf-use, n (%) 44 (23.7) 40 (22.9) 84 (23.3) 19 (19.0) mean ± sd czp 200 mg q2w (n=183) czp 400 mg q2w (n=173) all czp (n=356) placebo (n=97) sf-36 domain vitality 48.5 ± 9.8 47.6 ± 10.0 48.1 ± 9.9 47.2 ± 9.7 social functioning 45.4 ± 11.1 45.1 ± 11.0 45.2 ± 11.0 45.0 ± 11.7 role emotional 46.8 ± 10.4 46.1 ± 10.8 46.4 ± 10.6 46.7 ± 10.3 mental health 46.8 ± 10.7 46.3 ± 10.1 46.5 ± 10.4 44.9 ± 12.0 physical functioning 47.7 ± 9.6 49.1 ± 9.4 48.4 ± 9.5 48.5 ± 8.8 role physical 46.7 ± 9.5 47.3 ± 10.0 47.0 ± 9.7 47.1 ± 8.8 bodily pain 45.3 ± 10.4 46.6 ± 11.1 45.9 ± 10.7 45.5 ± 10.7 general health 47.1 ± 10.1 47.5 ± 9.3 47.3 ± 9.7 46.4 ± 10.4 study week 0 8 12 16 24 32 48 72 96 120 144 all czp 356 339 340 339 319 307 295 275 256 238 221 placebo 97 92 88 87 physical domainsmental domains 8 7 6 5 4 3 2 1 physical functioning role physical bodily pain general healthvitality social functioning role emotional mental health czp 200 mg q2w (n=149) czp 400 mg q2w (n=146) m e a n c h a n g e f ro m b a se lin e week 168 4832 72 12096 144 all czp placebo bodily pain role physical general health physical functioning 0 8 6 4 2 0 open-label period with possible dose adjustment 6 4 2 0 8 -1 m e a n c h a n g e f ro m b a se lin e week 160 8 4832 72 12096 144 all czp placebo role emotional social functioning mental health vitality 6 4 2 0 8 open-label period with possible dose adjustment -1 <pasi 50 initial treatment period (double-blinded) screening maintenance period safety follow-up open-label extension period (dose adjustment possible)a 48week 32 152160 40 144 mandatory at the investigator's discretion withdrawal ldb ≥pasi 50, <pasi 75 ldb <pasi 50 ≥pasi 75 ≥pasi 50 <pasi 75 <pasi 50 – withdrawn<pasi 50 – withdrawn placebo q2w ≥pasi 75 1:2:2 randomization czp 400 mg q2w escape: open-label czp 400 mg q2w ≥pasi 75 czp 200 mg q2w mental domains: vitality social functioning role emotional mental health 4 physical domains: physical functioning role physical bodily pain general health skin july 2021 1291 proof returned skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 441 brief article cutaneous metastasis of thymic carcinoma to the frontal scalp leon kou1, do, austin wong, do1, lily zhong, do1, sid danesh, md1 1danesh dermatology, beverly hills, ca thymic carcinomas (tc) are a rare and aggressive variant of thymic epithelial tumors. the symptoms of tc are often vague and caused by local invasion and mass effect. they rarely metastasize outside of the anterior mediastinum, but typically involves the lungs, lymph nodes, liver, pleura, or bones when it occurs.1,2 skin metastases are extremely rare and could easily be misdiagnosed as benign skin conditions such as localized dermatitis or infection. tcs lack pathognomonic histology and immunohistochemistry (ihc) features.3 ruling out differentials such as metastasis from other primary sites are often required before definitive diagnosis.4 to date, only a handful of articles have reported on cutaneous metastasis of tc and there is a scarcity of data on presentation, diagnosis, and management.5 we report a rare case of ihc confirmed cutaneous metastasis of tc. 53-year-old female presented to our dermatology clinic with an enlarging painful frontal scalp lesion for 1 year. it was previously treated as an infection with a course of antibiotics with subjective improvement to lesion size. the patient noted hair loss of the surrounding area within the past 6 months. she denied previous trauma or aggravating factors to the site. she denied all review of systems including possible symptoms of myasthenia gravis such as weakness of the ocular, respiratory, or bulbar muscles. her medical history was significant for tc with metastasis to the lung diagnosed 1 year ago. her tc workup began when vague superior vena cava syndrome symptoms first presented 2 years ago. the symptoms worsened over time and a lengthy outpatient workup led to the discovery of the mediastinal mass on cardiac mri. the patient underwent anterior mediastinotomy with surgical biopsy which revealed a diagnosis of thymic neoplasm, likely tc, with lung metastasis. abstract thymic carcinomas are a rare variant of thymic epithelial tumors. compared to thymomas, they are much more aggressive, difficult to treat, and have a higher mortality rate. metastasis outside of the mediastinum is rare and usually to sites such as the lung, lymph nodes, liver, pleura, or bones. we report a case of immunohistochemistry proven thymic carcinoma metastasis to the cutaneous surface of the frontal scalp in a 53-year-old asian female. introduction case report skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 442 she refused chemotherapy and further surgical resection and instead, underwent anterior mediastinum radiotherapy at 44 gy/22 fractions for 1 month with some decrease in mass size on repeat ct. previous biopsy results and imaging were unavailable for review. the lesion appeared as an isolated erythematous subcutaneous nodule with overlying telangiectasias at the mid frontal scalp with alopecia surrounding and overlying the area of the nodule (figure 1). due to the patient’s medical history of tc, the lesion was removed via excisional biopsy. figure 1. erythematous subcutaneous nodule with overlying telangiectasias at the mid frontal scalp with alopecia surrounding and overlying the area of the nodule pathology reported multiple lobules of dermal proliferation of neoplastic epithelioid cells with nuclear pleomorphism (figure 2). ihc staining was positive for ae1/ae3, p63, and pax8 and negative for ttf1 and synaptophysin (figure 3). cd5 and cd117 staining revealed positive staining for few lymphoid cells, but negative for epithelial cells. the results were consistent with metastatic tc to the mid frontal scalp. the patient was referred to oncology to investigate the extent of metastasis to other sites. figure 2. a) hematoxylin and eosin (h&e) showing multiple lobules of dermal proliferation of neoplastic epithelioid cells. magnification x 40. b) h&e showing tumor cells nuclear pleomorphism. magnification x 400. histologically, tcs usually lack features of a normal thymus and the lymphocytic components often seen in thymomas. tcs also display frank features of malignancy such as anaplasia, increased proliferative activity, and cellular atypia.6 primary tcs have no distinguishing histological features to separate them from metastasis of other discussion a b skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 443 figure 3. positive immunohistochemistry staining of tumor epithelioid cells for a) ae1/ae3 b) p63 c) pax8 magnification x 40. organ systems. notably, primary lung carcinomas must be ruled out due to proximity of presenting sites and similarity in histological appearance.4 ihc plays a vital role in distinguishing tcs from metastasis from other areas into the mediastinum despite tcs lacking a distinct ihc profile.3 cd5 and cd117 are widely used markers of tc.7 interestingly, our sample only had positive cd5 and cd117 staining for a few lymphocytes rather than strong, diffuse cytoplasmic staining of epithelial cells as previously reported cases of extra-thoracic tc metastasis.1,5 however, lack of cd5 and cd117 positive staining does not necessarily rule out tc. in a case series of 65 tc cases, only 39% and 65% stained positive for cd5 and cd117, respectively.8 another case series with 9 tc cases found similar results for cd5 ihc staining and hypothesized that using paraffin embedded tissue rather than frozen section for ihc decreased the sensitivity of positivity.9 ultimately, investigations, with larger sample size, into the use of cd5 and cd117 for tc identification may be helpful and explain the reason behind our results. the diagnosis of cutaneous metastasis of tc in our patient was made based on previous imaging, surgical biopsy results, and the remaining ihc results. except for cd5 and cd117, our ihc results correlate with a previously reported tc cutaneous metastasis case.5 positive pax8 staining, found in approximately 77% of tcs, but rarely expressed in primary lung cancers, supported the diagnosis of tc with metastasis to the lungs and our current diagnosis of tc metastasis to the skin.10,11 tcs generally stain negative for ttf-1 and synaptophysin and our negative results further rule out the possibility of lung, thyroid, or neuroendocrine tumor metastasis.12 positive staining for p63, found in normal thymus gland and thymic epithelial tumors, and pancytokeratin (ae1/ae3), typically positive in tcs, further support our diagnosis.3 our patient’s skin lesion appeared 1 month after discovery of the mediastinal mass by cardiac mri and because it was left uninvestigated, the lesion worsened over 1 year with increased size, pain, and alopecia of the surrounding area. generally, cutaneous metastasis of internal tumors is rare. they can be cosmetically devastating and are usually poor prognostic factors. our patient is at minimum stage iiib, with an incompletely resected tc, which puts her 5year overall survival at approximately 31%.4 a b c. skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 444 tc cutaneous metastases are difficult to diagnose by gross appearance alone and even pathology may find it difficult without proper context. tc metastasis to sites such as the parotid and small intestine have been reported.1,2,5 current nccn guidelines suggest clinical correlation on using pet-ct or mri during workup.4 more data is needed to develop an algorithmic approach to using pet-ct and mri to rule out metastasis to other sites and organs due to the tumor’s aggressiveness. tc skin metastasis is rare and could be misdiagnosed for a benign skin condition. careful consideration of the patient's history and clinical presentation was necessary to have tc metastasis as a differential. without using immunohistochemistry stains, diagnosis and ruling out metastasis from other primary cancers would have been difficult if not impossible. conflict of interest disclosures: none funding: none corresponding author: leon kou, do 240 s. la cienega blvd beverly hills, ca 90211 phone: 909-859-9885 email: k.leon@ucla.edu references: 1. huang p, huang r, xiao w, et al. ectopic thymic carcinoma in parotid gland: a rare case and review of literature. int j clin exp pathol. 2019;12(1):384-388. 2. yuan y, pu h, pang m, liu y, li h. thymic carcinoma metastasize to the small intestine: a case report. bmc gastroenterol. 2020;20. doi:10.1186/s12876-020-01505-7 3. weissferdt a, moran ca. immunohistochemistry in the diagnosis of thymic epithelial neoplasms. appl immunohistochem mol morphol. 2014;22(7):479-487. doi:10.1097/pai.0b013e3182a53856 4. national comprehensive cancer network (nccn). clinical practice guidelines in oncology: thymomas and thymic carcinomas. version 1.2021. accessed at https://www.nccn.org/professionals/physician_gls/ pdf/thymic.pdf on april 21, 2021. 5. choi sj, rho nk, yang jm, lee es. a case of cutaneous matestasis originating from thymic carcinoma. annals of dermatology. 2016;14(4):230-234. 6. eng ty, fuller cd, jagirdar j, bains y, thomas cr. thymic carcinoma: state of the art review. int j radiat oncol biol phys. 2004;59(3):654-664. doi:10.1016/j.ijrobp.2003.11.021 7. kriegsmann m, muley t, harms a, et al. differential diagnostic value of cd5 and cd117 expression in thoracic tumors: a large scale study of 1465 non-small cell lung cancer cases. diagn pathol. 2015;10. doi:10.1186/s13000-015-0441-7 8. weissferdt a, moran ca. thymic carcinoma, part 1: a clinicopathologic and immunohistochemical study of 65 cases. am j clin pathol. 2012;138(1):103-114. doi:10.1309/ajcp88fztwanlrcb 9. berezowski k, grimes mm, gal a, kornstein mj. cd5 immunoreactivity of epithelial cells in thymic carcinoma and castle using paraffinembedded tissue. am j clin pathol. 1996;106(4):483-486. doi:10.1093/ajcp/106.4.483 10. jeong jh, kim ny, pyo j-s. analysis of pax8 immunohistochemistry in lung cancers: a metaanalysis. j pathol transl med. 2020;54(4):300309. doi:10.4132/jptm.2020.06.08 11. weissferdt a, moran ca. pax8 expression in thymic epithelial neoplasms: an immunohistochemical analysis. am j surg pathol. 2011;35(9):1305-1310. doi:10.1097/pas.0b013e3182260735 12. zamecnik j, kodet r. value of thyroid transcription factor-1 and surfactant apoprotein a in the differential diagnosis of pulmonary carcinomas: a study of 109 cases. virchows arch. 2002;440(4):353-361. doi:10.1007/s00428001-0552-2 conclusion acknowledgements study funded by galderma research & development, snc, and editorial/poster support provided by galderma laboratories, l.p. methods study 1 • a 12 o tetradecanoylphorbol-13-acetate (tpa)-induced inflammation model was designed to investigate the anti-inflammatory effect of ivm in balb/c byj rj mice. • ear edema was induced in the right ear of female mice by topical application of tpa 0.01%, followed by treatment with: topical vehicle ivm (0.1% to 1%) br (0.2%) ivm+br an anti-inflammatory control (betamethasone valerate 0.01% or indomethacin 5%) • right ear thickness (μm) was measured using a micrometer preand 6 hours after tpa application study 2 • this was a multicenter, randomized, double-blind, vehicle-controlled, and parallel group comparison study that included subjects with moderate to severe rosacea (investigator global assessment [iga] ≥3, scale 0-4), characterized by persistent diffuse moderate to severe erythema (clinician erythema assessment [cea] ≥3, scale 0-4) and inflammatory lesions ([il] 15-70 papules/pustules). • treatments randomized 1:1:2, 2 active and 1 vehicle group, respectively ivm (1%) + br (0.33%) active treatment groups: · ivm+br/12w subgroup (n = 49): once daily ivm + br for 12 weeks · ivm+br/8w subgroup: (n = 46): once daily ivm + br vehicle for 4 weeks; followed by ivm + br for the remaining 8 weeks vehicle group: · once daily ivm vehicle and br vehicle for 12 weeks (vehicle group, n = 95) a daily skin care regimen of gentle cleanser, moisturizing lotion and facial moisturizer spf 15 sunscreen • efficacy and safety endpoints iga success (0/1 [clear/almost clear], 5-point scale, week 12, 3 hours after br application), iga at each visit, cea, 100% reduction in il count, and subject global improvement of rosacea aes were monitored throughout the study results study 1 • anti-inflammatory synergy was observed between ivm and br in the mouse model • ivm+br had a similar effect on ear edema at 6 hours when compared with a potent corticosteroid or nsaid (figure 1 and 2) study 2 • subjects who began ivm+br treatment at baseline had an improved rate of iga success when compared with both vehicle and subjects who began br treatment at week 8 (figure 3) • subjects who began ivm+br treatment at baseline had improved cea assessments at week 12 when compared with both vehicle and subjects who began br treatment at week 8 (figure 4) • subjects who began ivm+br treatment at baseline were more likely to achieve a 100% reduction in lesions at week 12 when compared with both vehicle and subjects who began br treatment at week 8 (figure 5) safety • only 8 treatment-related aes in 6 subjects (3.2%) were reported; none were serious or severe. • one related ae leading to discontinuation (allergic dermatitis on the chest) was reported in the ivm+br/8w group. • related worsening of rosacea was observed in similar frequency with 1 (2.2%) ae in the active ivm+br groups vs. 3 (2.1%) aes in the vehicle group. introduction • rosacea is often characterized by persistent centrofacial erythema and recurrent inflammatory papules/pustules the pathophysiology of papulopustular rosacea (ppr) is not fully understood multiple immune, inflammatory, and vascular processes are likely involved • ivermectin 1% (ivm) cream has anti-inflammatory properties and has been shown to be effective against papules/pustules of erythema1,2,3 ivermectin treatment reduces pro-inflammatory cytokines and chemokines, inhibits leukocytes, and modulates the cathelicidin pathway • brimonidine 0.33% (br) gel has been shown to be effective against persistent facial erythema2 brimonidine is an alpha 2 adrenergic agonist responsible for vasoconstriction of superficial blood vessels • two recent studies investigate ivm and br when used in combination for the treatment of ppr the anti-inflammatory properties of ivermectin and brimonidine in the treatment of papulopustular rosacea linda stein gold, md1; edward lain, md2; alison harvey, phd, ms3 1department of dermatology, henry ford medical center, detroit, mi, usa; 2austin institute for clinical research, pflugerville, tx; 3galderma laboratories, l.p., fort worth, tx soo.p-rd105069-03 summary • rosacea therapy requires a global and patient specific approach that targets its varied symptoms and mechanisms, including both the inflammatory pathways and vascular components of the disease. • in the mouse model: – ivm significantly reduced ear skin swelling – br acted synergistically with ivm to enhance anti-inflammatory activity • in the clinical study: – simultaneous administration of ivm 1% cream with br 0.33% gel demonstrated superior efficacy compared to their respective vehicles for the treatment of moderate to severe rosacea – the ivm + br association was well tolerated, with less than 5% related aes • the regimen of ivm+br is a safe and effective option for the comprehensive management of this complex disease • these studies suggest that initiating rosacea therapy with ivm+br, along with a complete daily skin care regimen, may improve and accelerate the efficacy of ivm treatment, without impairing tolerability • treating with ivm+br from the start was more effective than an initial period of ivm treatment alone followed by ivm+br references 1. stein l, kircik l, fowler j, et al. efficacy and safety of ivermectin 1% cream in treatment of papulopustular rosacea: results of two randomized, double-blind, vehicle-controlled pivotal studies. j drugs dermatol. 2014;13:316-323. 2. abokwidir m, et al. j dermatol treat. 2015;26(4):379-80. 3. thibaut de menonville s, et al. dermatol ther (heidelb). 2017 epub 4. fowler j jr, jackson m, moore a, et al. efficacy and safety of once-daily topical brimonidine tartrate gel 0.5% for the treatment of moderate to severe facial erythema of rosacea: results of two randomized, double-blind, and vehiclecontrolled pivotal studies. j drugs dermatol. 2013;12:650-656. 5. di nardo a, et al. j am acad dermatol. 2016 jun;74(6):1086-92. 200 300 400 500 600 vehicle betamethasone valerate ivermectin 0.3%+brimonidine 0.2% ivermectin 0.3% brimonidine 0.2% * * * * * ea r t hi ck ne ss (µ m ): m ea n + / sd * p . 0 1 * * p < . 0 0 1 200 250 300 350 400 450 500 vehicle indomethacin ivermectin 1% * * * * * * * * p . 0 1 * * p < . 0 0 1 ea r t hi ck ne ss (μ m ): m ea n + / sd ivermectin 1%+brimonidine 0.2% brimonidine 0.2% 4.1 22.4 42.9 61.2 4.3 13.0 30.4 50.0 5.3 9.5 24.2 36.8 0 10 20 30 40 50 60 70 baseline week 4 week 8 week 12 pe rce nt o f s ub je cts a ch ie vin g ig a su cce ss (i ga 0 o r 1 ) ivm+br/12w (n = 46) ivm+br/8w (br vehicle) vehicle (n = 95) ivm+br/8w (br active) p = .003 p = .02 p = .04 (n = 49) 15.1 29.3 29.5 25.6 39.0 45.5 0 10 20 30 40 50 60 70 80 clear skin almost clear 40.7 success 68.3* success 75.0* success pe rce nt o f s ub je cts ivm+br 12wvehicle ivm+br 8w * p = .001 4.2 6.5 16.3 0 2 4 6 8 10 12 14 16 18 vehicles ivm + br / 8 weeks ivm + br / 12 weeks pe rc en t o f s ub je cts w ith 1 00 % r ed uc tio n in in fla m m at or y l es io n co un t p = .015 figure 1. ear edema measured 6 hours post-treatment figure 2. ear edema measured 1 hour post-treatment figure 3. iga success figure 4. cea at week 12, hour 3 figure 5. percent of subjects achieving 100% il reduction betamethasone valerate is a potent corticosteroid. indomethacin is a non-steroidal anti-inflammatory drug (nsaid). betamethasone valerate is a potent corticosteroid. indomethacin is a non-steroidal anti-inflammatory drug (nsaid). fc17postergaldermasteingoldantiinflammatoryproperties.pdf skin may 2019 volume 3 issue 3 copyright 2018 the national society for cutaneous medicine 176 clinical management recommendations how to manage melasma seemal r desai, md1, maureen ezekor, bs2 1department of dermatology, university of texas southwestern medical center, dallas, tx 2university of texas medical branch, galveston, tx melasma, previously known as chloasma, is a commonly acquired hypermelanosis characterized by symmetric, reticulated, hyperpigmentations of sun-exposed areas of the skin, particularly the face. melasma has a higher prevalence in women and patients of darker skin tones, although it can occur in all skin types. the dyspigmentation caused by melasma often has a negative psychosocial impact on those affected with the condition as demonstrated by patient-reported anhedonia, decreased self-esteem, dissatisfactory mood, and impairment in social and occupational functioning.1 the pathogenesis of melasma is still unclear, however various factors have been implicated and well supported such as ultraviolet radiation exposure, genetic predisposition, and hormonal influences.2 due to the incomplete understanding of its pathogenesis and the high recurrence rate, melasma remains a difficult disorder to manage resulting in physician frustration and patient dissatisfaction. nevertheless, several topical, oral, and procedural treatment options are available with varying mechanisms of action addressing the multifactorial nature of the disorder. the purpose of this article is to provide a framework for dermatologists to use to approach and clinically manage this common, yet therapeutically challenging, condition. evidence-based studies recommend that first line therapies for melasma incorporate topical agents, including photoprotection.3 hydroquinone is historically the gold standard treatment for melasma and remains one of the most effective monotherapies. it works by inhibiting tyrosinase, thereby preventing the conversion of dopa into melanin. hydroquinone can cause skin irritation and very rarely lead to ochronosis with prolonged or highly concentrated applications.4 it should be avoided in pregnant and breastfeeding women. although hydroquinone is the cornerstone of topical therapy, multiple studies have demonstrated superiority of topical combination therapies over monotherapy.2 triple combination therapy (tct) combines hydroquinone with a retinoid and a topical corticosteroid in varying concentrations.4 the corticosteroid serves as an anti-inflammatory agent while the retinoid is hypothesized to increase keratinocyte turnover.2 although more effective, tct has been associated what topical therapies are available? skin may 2019 volume 3 issue 3 copyright 2018 the national society for cutaneous medicine 177 with increased erythema and skin irritation.3 other topical tyrosinase inhibitors such as azelaic acid, kojic acid, and ascorbic acid, for example, may also be used but have demonstrated inferiority to hydroquinone as monotherapies.2 last but not least, daily photoprotection is a critical component in the treatment of melasma. broad spectrum sunscreens that combine uva and uvb filters with visible light blockers, such as iron oxide, are preferable to broad-spectrum uv filters alone, with the former group showing greater improvement and reduced relapses.2,4, oral therapies have emerged as effective treatment options for melasma, and often as an adjunctive to topical therapies. the hemostatic agent tranexamic acid (ta) is arising as a promising oral therapy to treat this disorder, as shown by recent studies.5,6 ta is a synthetic derivative of lysine and functions by blocking the conversion of plasminogen into plasmin, leading to a downstream effect of reduced production of melanocyte-stimulating hormone (msh). 4 ta is gaining attention for melasma because studies have shown effectiveness with frequently minimal side effects.5,6 the side effect profile for oral ta can include gastrointestinal irritation, headache, tinnitus, changes in menstrual cycle, and rarely deep vein thrombosis (dvt).2,5 due to the serious, though rare, side effect of dvt, patients must be screened for risk of thrombosis prior to initiating this treatment. a very comprehensive detailed history and physical examination are recommended for dermatologists prescribing this oral therapy. patients must be screened for smoking, use of oral contraceptives, history of miscarriages, plans of future pregnancy, and other important historical clues. if any the above, and/or other pertinent details are elucidated, then the patient would not be considered a candidate for ta. in addition to the oral form, ta has been used in other delivery routes including topical, intradermal, and microinjection.6 clinical trials have demonstrated similar efficacy of topical ta to hydroquinone-based formulations.4 other oral agents such as polypodium leucotomos (pl), and even glutathione, have been discussed in the literature as possible adjunctive treatments for melasma and work by inhibiting reactive oxygen species. pl, a species of fern, protects against uv-induced damage, and oral ingestion has shown improvement in melasma with minimal to no side effects.8 recently glutathione has been used as a depigmenting agent and is postulated to have this effect by inactivating melanocyte tyrosine kinase and promoting pheomelanin production from eumelanin.7 treatment with oral glutathione is well tolerated with only few, mild reported side effects of flatulence, pruritus, erythema, and fatigue.8 however, the low oral bioavailability of glutathione leads to reduced plasma concentration and thus questionable overall effectiveness. this has led to a dramatic increase in intravenous usage of glutathione in many parts of the world, and has led to significant controversy due to safety issues. the us food & drug administration, in fact, has a warning about the usage of intravenous glutathione (https://www.fda.gov/forconsumers/consu merupdates/ucm460788). what is the role of oral therapy? https://www.fda.gov/forconsumers/consumerupdates/ucm460788 https://www.fda.gov/forconsumers/consumerupdates/ucm460788 skin may 2019 volume 3 issue 3 copyright 2018 the national society for cutaneous medicine 178 in recent reports of literature, procedures such as chemical peels, microneedling, and lasers have been used as adjunctive and maintenance therapies for melasma. chemical peels may be helpful in the epidermal variant of melasma through its superficial effects of helping remove melanin from keratinocytes and arresting melanosome transfer to keratinocytes.9 priming with a topical agent such as hydroquinone or retinoids for at least four weeks is required in order to reduce complications and promote uniform penetration.9 moreover, studies illustrate faster and better results when used in combination with topical therapy.9 another procedural treatment is microneedling. in mesotherapy, small needles are used to create punctures in the skin to deliver drugs intradermally. the exact mechanism that stimulates skin lightening is unknown, nevertheless the procedure has demonstrated improvement in cases of recalcitrant melasma.10 finally, lasers and other light treatments have been used to treat melasma with varying degrees of success. they should only be considered after a patient has failed treatment with topical therapies and chemical peels.11 although there is an array of lasers and light therapies available, it is important that patients are advised on the probability of recurrence and post inflammatory or rebound pigmentation.11 other new oral and topical treatments include melatonin, cysteamine, methimazole, flutamide, and pigment-correcting serum.4 while these agents have produced positive results, additional well-designed clinical trials are needed to substantiate their safety and efficacy. although melasma is a difficult condition to treat, there are several available treatment options. to determine the proper treatment, dermatologists should consider the patient’s melasma-specific medical history, skin type, and other concomitant dermatologic and medical conditions. for example, numerous reports of thyroid dysfunction associated with refractory melasma have also been found in the literature. furthermore, it is essential to establish rapport with patients in order to build a therapeutic alliance with reasonable goals and expectations. given this, we suggest the following approach when discussing melasma with patients: � melasma is a common chronic and relapsing acquired hyperpigmentation that is difficult to treat and has a negative psychosocial impact on the lives of affected patients. � topical therapy, particularly combination therapy with hydroquinone, is the mainstay of treatment and should be used as the first-line option. � daily photoprotection with broadspectrum sunscreen is key to the management and should be incorporated into every treatment regimen. � oral therapies and procedural treatments can be used as adjunctive therapies to topical treatments after topical treatments have failed. � a multimodality approach addressing the multifactorial nature of the disorder is optimal. what procedures have demonstrated improvement? other emerging therapies how to discuss melasma with patients skin may 2019 volume 3 issue 3 copyright 2018 the national society for cutaneous medicine 179 � uv and visible light should be avoided to prevent flares and exacerbation of melasma. � several new therapies are emerging as promising agents to treat melasma, but further clinical studies are warranted to investigate their efficacy. conflict of interest disclosures: none. funding: none. corresponding author: seemal r desai, md university of texas southwestern medical center dallas, tx seemald@yahoo.com references: 1. becker, s., schiekofer, c., vogt, t., & reichrath, j. (2017). melasma: ein update zu klinik, therapie und prävention (leitthema). der hautarzt, 68(2), 120-126. 2. ogbechie-godec, o. a., & elbuluk, n. (2017). melasma: an up-to-date comprehensive review. dermatology and therapy, 7(3), 305-318. 3. rivas, s., & pandya, a. g. (2013). treatment of melasma with topical agents, peels and lasers: an evidencebased review. american journal of clinical dermatology, 14(5), 359-376. 4. grimes, p. e., ijaz, s., nashawati, r., & kwak, d. (2019). new oral and topical approaches for the treatment of melasma. international journal of women's dermatology, 5(1), 30-36. 5. colferai, m. m. t., miquelin, g. m., & steiner, d. (2018). evaluation of oral tranexamic acid in the treatment of melasma. journal of cosmetic dermatology. 6. zhang, l., tan, w. q., fang, q. q., zhao, w. y., zhao, q. m., gao, j., & wang, x. w. (2018). tranexamic acid for adults with melasma: a systematic review and meta-analysis. biomed research international, 2018. 7. iraji, f., nasimi, m., asilian, a., faghihi, g., mozafarpoor, s., & hafezi, h. (2019). efficacy of mesotherapy with tranexamic acid and ascorbic acid with and without glutathione in treatment of melasma: a split face comparative trial. journal of cosmetic dermatology. 8. juhasz, m. l., & levin, m. k. (2018). the role of systemic treatments for skin lightening. journal of cosmetic dermatology, 17(6), 1144-1157. 9. sarkar, r., arsiwala, s., dubey, n., sonthalia, s., das, a., arya, l., ... & godse, k. (2017). chemical peels in melasma: a review with consensus recommendations by indian pigmentary expert group. indian journal of dermatology, 62(6), 578. 10. lima, e. v., lima, m. m. d., paixão, m. p., & miot, h. a. (2017). assessment of the effects of skin microneedling as adjuvant therapy for facial melasma: a pilot study. bmc dermatology, 17(1), 14. 11. trivedi, m. k., yang, f. c., & cho, b. k. (2017). a review of laser and light therapy in melasma. international journal of women's dermatology, 3(1), 11-20. mailto:seemald@yahoo.com skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 344 brief articles 61-year-old white female with a non-healing ulcerated ankle mass christopher lowther, md mrcp1, troy fiddler, md phd2, ian a. whitcroft, mbchb mrcp3, juanita sapp, md4, etan marks, do5, clay cockerell, md5 1edin, big horn basin skin center, cody wyoming 2frontier cancer ctr., st. vincent healthcare, billings, montana 3weston general hospital, weston-supermare, united kingdom 4heritage healthcare, powell, wyoming 5cockerell dermatopathology, dallas, texas a 61-year-old white female presented with a four month history of a 3.5 cm in diameter non-healing ulcerated mass on her right ankle. the patient also had two small lesions, both on her right lower leg measuring 5 mm in diameter. her ankle was painfully inflamed. lymphadenopathy was noted in the right inguinal area. the rest of her physical exam was unremarkable. all three lesions on her right leg underwent biopsy. the only abnormal laboratory tests were a hemoglobin of 10.9 g/dl and ferritin of 9 ng/ml (eight 252 ng/ml). pre-biopsy impression was a metastatic squamous cell carcinoma or pyoderma gangrenosum. the patient had a strong family history for colon cancer without a history of prior inflammatory bowel disease. all three lesions were biopsied and demonstrated a malignant basophilic neuroendocrine neoplasm, either primary or metastatic. immunoperoxidase stains showed strong positivity for cytokeratin 20 abstract merkel cell carcinoma is a rare cutaneous carcinoma from the tactile merkel cells. with fewer than half the patients surviving more than one year and fewer than 20% surviving beyond five years. these tumors are rarely suspected until the biopsy results return. polyoma virus is associated with up to 80% of the tumors. 53% present on the head and neck and 35% present on the extremities while larger lesions are exceedingly rare in either location. recently, a newly approved drug, avelumab, has shown tumor response in patients with some patients experiencing complete remission. history physical examination laboratory data histopathology skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 345 and synaptophysin with a negative cytokeratin cocktail and ttf-1. a neuroendocrine carcinoma was diagnosed, likely a merkel cell carcinoma, possibly metastatic. computerized axial tomography revealed 6 mm non-calcified pulmonary nodules. there was a small 7 mm abnormality in the liver. however, a complete body pet imaging was performed. focal hypermetabolic activity was noted at the left base of the tongue, with no hypermetabolic activity in the lungs. there was no evidence of mediastinal or hilar lymphadenopathy. liver, gallbladder, spleen, pancreas, adrenal glands, kidney and vessels were unremarkable. there was right inguinal lymphadenopathy, with the largest lymph node measuring 19 x 21 mm, with hypermetabolic activity and a maximum suv value of 4.1. this was suspicious for metastasis. additionally, lymph nodes were seen along the right mid-thigh and medial lower leg with hypermetabolic activity. diffuse soft tissue thickening around the distal tibia and fibula around the ankle with a soft tissue defect and hypermetabolic activity with a maximum suv value at 9.4 at the lateral ankle which were also suspicious for known carcinoma. a subsequent biopsy of the right inguinal lymph node demonstrated merkel cell carcinoma. metastatic merkel cell carcinoma, staging t2, n3, mo equating to stage iiib. the case was presented at st. vincent healthcare tumor board. the recommendation was to proceed with systemic therapy without surgery due to the extent of disease. the newly approved pd-l1 drug for merkel cell carcinoma, avelumab was started. with the start of cycle four, the right ankle had almost completely resolved. the treatment was tolerated without any complications. there was no dose modification. follow-up axial tomography of the chest, abdomen and pelvis and right lower leg was ordered and is currently pending. figure 1. ulcerated mass and two biopsy sites figure 2. merkel cell ulcerated mass clinical course diagnosis skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 346 figure 3. composition of low and high power showing classic merkel cell features of a dermal infiltration with monotonous round tumor cells with vesicular nuclei with finely granular and dusty chromatin and multiple nucleoli. also there are several apoptotic nuclei and frequent mitotic figures. additionally, a stain for cytokeratin 20 is diffusely positive. certain sweat gland carcinomas of the skin, first described by toker in 1972 were later found to have dense corps granules of the tactile merkel cells.1,2,3,4 upon presentation 66% of patients had local disease, 27% nodal involvement and 7% distant metastasis.2,4 the majority of patients with merkel cell carcinoma are 70 years or older with an increased incidence in renal transplant patients, chronic lymphocytic leukemia and hiv.1 polyomavirus is associated with up to 80% of tumors.4 the primary lesion of merkel cell carcinoma is often absent of distinctive clinical characteristics and is rarely suspected at the time of biopsy. it often presents as a rapidly growing reddish blue dermal papule or nodule.5 avelumab, the human anti-pd-l1 antibody, is the first immunotherapy approved for metastatic merkel cell carcinoma for adult and pediatric patients 12 years and older. metastatic merkel cell carcinoma is a rare and aggressive skin cancer with fewer than half the patients surviving more than one year and fewer than 20% surviving beyond five years.6 immunochemistry is extremely helpful as merkel cells are almost impossible to see on light microscopy. without immunohistochemical stains the tumor is nearly impossible to differentiate from other neuroendocrine carcinomas, such as metastatic small cell carcinoma of the lung.5 ck 20 is the predominant tool used by pathologists and stains approximately 80 to 90% of all merkel cell carcinomas with a distinctive perinuclear dot–like pattern.5,7 approximately 53% of merkel cell carcinomas occur in the head and neck; 35% occur in the extremities.8 in the javelin merkel 200, a phase 2 clinical trial, at the median follow-up of 16.4 months, of which 88 patients had been enrolled and treated with avelumab, there was an overall response rate of 33%(29 patients). the partial response was 22% with a complete response rate of 11%. 86% of tumor responses lasted at least six months(25 patients) and 45% lasted at least 12 months (13 patients).8 conflict of interest disclosures: none funding: none corresponding author: christopher lowther, md mrcp chrislowther@qwestoffice.net references: 1. toker c. trabecular carcinoma of the skin. arch of dermatol 1972; 105:107 – 110. 2. han s, north j, canavan t, et al. merkel cell carcinoma. hematol oncol clin n amer. 2012; 26:1351 – 1374 points of emphasis mailto:chrislowther@qwestoffice.net skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 347 3. goessling, w, mckee p, mayer r. merkel cell carcinoma. j clin oncol. 2002; 20:588 – 598. 4. oram c , bartus c s, purcell s. merkel cell carcinoma: a review. cutis. 2016 volume 97, 4 to 90 – 295 5. wang t, byrne, p, et al, semin cutan med surg. 2011 mar:30 (1) 48-56 6. lemos b, storer b, lyer j, et al. pathologic nodal evaluation approves prognostic accuracy and merkel cell carcinoma; j amer acad derm. 2010; 63(5): 751 – 761. 7. bobos m, hytiroglou p, kostopoulos i, et al. immunohistochemical distinction between merkel cell carcinoma and small cell carcinoma of the lung. dermatopathol. 2006; 28:99 – 104. (pub med) 8. pearson, j , meyers, a skin cancer – merkel cell carcinoma, medscape updated march 27, 2017 skin july 2018 volume 2 issue 4 copyright 2018 the national society for cutaneous medicine 236 brief article evolution of a doxycycline-induced phototoxic rash with an unusual distribution katrina kesterson ms a , adrian subrt md b , michael wilkerson md b a university of tennessee health science center, college of medicine, memphis, tn b university of texas medical branch, department of dermatology, galveston, tx a 62-year-old caucasian female with a history of rosacea presents for evaluation of a rash on her dorsal fingers. she has been taking doxycycline 100 mg by mouth daily for rosacea which has kept it well-controlled. she states she wore fingerless gloves but otherwise was covered by clothing during a recent 21-day motorcycle trip. she did not use sunscreen on her hands. the rash began on the third day of the trip and lasted approximately a month while she was taking doxycycline. of note, she also had acrylic fingernails at the time. by the time she arrived at the dermatology clinic the rash has resolved, but she presents with numerous photos depicting a severe phototoxic reaction of the distal dorsal fingers including initial erythema and edema on day 3 (figure 1), blistering on day 7 (figure 2) which led to well-demarcated areas of desquamation on an erythematous base (figure 3) several days later. the rash completely resolved after one month. interestingly, the acrylic on her fingernails may have prevented the development of onycholysis. she continued to take doxycycline until she presented in clinic and was advised to discontinue taking the drug to prevent another episode of phototoxicity. abstract commonly used in clinical practice, doxycycline has been known to produce a cutaneous phototoxic reaction in combination with sunlight. several mechanisms have been proposed to contribute to its pathogenesis such as uva oxidation of cellular components, the formation of photoproducts, and altered melanogenesis. we describe a case of a phototoxic rash in a patient taking doxycycline 100 mg daily for the treatment of rosacea. we present several photos of the rash from erythema to desquamation several weeks later. the clinical presentation of a doxycycline-induced phototoxic rash varies from a sunburn like sensation to diffuse erythematous plaques on sun exposed areas. treatment involves discontinuing the drug and providing symptomatic relief. although sunscreen may prevent a doxycyclineinduced phototoxic reaction, it is important to educate the patient to use a sunscreen with protection in the 340-400 nm range in which phototoxic reactions are thought to occur. as doxycycline-induced phototoxicity is poorly understood, it may be best to advise the patient to avoid sun exposure altogether while taking the drug. case report skin july 2018 volume 2 issue 4 copyright 2018 the national society for cutaneous medicine 237 figure 1. erythema and edema of the dorsal fingers on day 3 of symptoms. figure 2. blistering and erythema on day 10. figure 2. well-demarcated areas of desquamation on an erythematous base. skin july 2018 volume 2 issue 4 copyright 2018 the national society for cutaneous medicine 238 although several mechanisms have been described in literature, the pathogenesis of doxycycline-induced phototoxicity is poorly understood. uva oxidation of cellular components such as the cell membrane, dna, rna, ribosomal proteins, and mitochondria by a singlet oxygen may be a contributing factor. secondly, the formation of tetracycline photoproducts causes an increase in the absorption of visible radiation (>400 nm) that may also damage the skin. 1 in addition, uva in combination with doxycycline increases melanogenesis, affects melanocyte viability, and reduces antioxidant enzymes in a dose-dependent fashion. 2 although melanin absorbs uv radiation and acts as an antioxidant, it may oxidize at higher doses which leads to additional cell damage. 3 the clinical presentation of doxycycline induced phototoxicity may vary from a sunburn-like sensation to diffuse erythematous plaques on sun-exposed areas. 4,5 the rash generally resolves within 10-14 days after discontinuation of the drug. 5 in addition, several case reports of onycholysis due to doxycycline induced phototoxicity have been described in adults and children. onycholysis of the nails presents as a crescent-shaped separation of the distal nail bed affecting several or all sun-exposed nails that may occur up to two weeks after discontinuation of the drug. 6 based on studies in current literature, the incidence of doxycycline phototoxicity follows a dose-dependent trend. in patients taking 100 mg/day of doxycycline, a phototoxic reaction was observed in 16% of patients (n=135). 4 in patients taking a 150 mg/day dose, the incidence was 20% (n=30). 5 in patients taking 200 mg/day of doxycycline, the incidence varied among studies, but was observed to be as high as 42% in a study comparing 150 mg to a 200 mg per day dose (n=76). 5 although sunscreen may prevent a doxycycline-induced phototoxic reaction, it is important to educate the patient on using a sunscreen with an appropriate range of protection. in one study, 16% (n=135) of troops deployed to an island of east timor within the malaysian archipelago had a phototoxic reaction to doxycycline (100 mg daily) prescribed for malaria prophylaxis while using sunscreen. the sunscreen applied by the troops had a sun protection factor of 15 and contained oxybenzone 3% as its only protectant against uva. 4 oxybenzone partially absorbs uva radiation up to 360 nm. 7 phototoxic eruptions, however, are thought to be due to radiation in the uva1 spectrum of 340-400 nm. 8 zinc oxide may be a better choice of sunscreen as it is the only sunscreen that offers protection against uvb and uva radiation up to 400 nm. 7 limited data exists on dermatologists’ recommendations regarding sunscreen as well as patient perception and compliance. based on a study by farberg et al. surveying 156 dermatologists, all recommended an spf greater than 30 and the majority considered broad-spectrum coverage an important characteristic when recommending sunscreen. 9 in a patient who might be on doxycycline long-term, it may be useful to educate the patient on applying a broad-spectrum formulation, protecting commonly missed areas such as the hands, frequent application, and covering sunexposed areas with clothing. additional discussion skin july 2018 volume 2 issue 4 copyright 2018 the national society for cutaneous medicine 239 studies would be useful to determine the most effective sunscreen formulation and sun protection factor to prevent doxycycline phototoxicity. conflict of interest disclosures: none funding: none corresponding author: katrina kesterson, ms uthsc, college of medicine 910 madison ave, #1002 memphis, tn 38103 901-448-5529 (office) kkesters@uthsc.edu references: 1. hasan t, kochevar ie, mcauliffe dj, et al. mechanism of tetracycline phototoxicity. journal of investigative dermatology. 1984;83(3):179-183. 2. rok j, buszman e, beberok a, et al. modulation of melanogenesis and antioxidant status of melanocytes in response to phototoxic action of doxycycline. photochemistry and photobiology. 2015;91(6):1429-1434. 3. wood sr, berwick m, ley rd, et al. uv causation of melanoma in xiphophorus is dominated by melanin photosensitized oxidant production. proceedings of the national academy of sciences. 2006;103(11):4111-4115. 4. lim d, murphy g. high-level ultraviolet a photoprotection is needed to prevent doxycycline phototoxicity: lessons learned in east timor. british journal of dermatology. 2003;149(1):213-214. 5. layton a, cunliffe w. phototoxic eruptions due to doxycycline-a dose-related phenomenon. clinical and experimental dermatology. 1993;18(5):425-427. 6. rabar d, combemale p, peyron f. doxycycline-induced photoonycholysis. journal of travel medicine. 2006;11(6):386-387. 7. baron e, stevens s. sunscreens and immune protection. british journal of dermatology. 2002;146(6):933-937. 8. bjellerup m, ljunggren b. differences in phototoxic potency should be considered when tetracyclines are prescribed during summer-time. a study on doxycycline and lymecycline in human volunteers, using an objective method for recording erythema. british journal of dermatology. 1994;130(3):356-360. 9. farberg as, glazer am, rigel ac, white r, rigel ds. dermatologists’ perceptions, recommendations, and use of sunscreen. jama dermatology. 2017;153(1):99. skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 693 brief article successful use of apremilast in psoriasiform dermatitis refractory to biologics christopher s yang, ba1, victor quan, md1, ahmad amin, md1 1department of dermatology, northwestern university feinberg school of medicine, chicago, il psoriasis is a common immune-mediated disease that can affect the skin, nails, and joints, seen in approximately 2% of the population. the most common form of the disease is chronic plaque psoriasis (psoriasis vulgaris), which presents as sharply demarcated erythematous plaques with silvery scales. histologic hallmarks include epidermal acanthosis, parakeratosis, and inflammatory infiltrate.1 management is usually comprised of topical therapy and/or systemic therapy, either biologic or nonbiologic. biologic therapies for psoriasis include tnf-alpha inhibitors, as well as interleukin (il)-12/-23, il-23, and il-17 inhibitors.2 nonbiologic systemic therapies include methotrexate, cyclosporine, acitretin, and phosphodiesterase-4 inhibitors.3 we present the case of a 34-year-old female with a history of exercise-induced asthma and a 16-year history of psoriasiform dermatitis without joint involvement. at age 18, she presented with erythematous pruritic plaques with silvery scale symmetrically on the dorsal feet, and a clinical diagnosis of moderate to severe psoriasis was made. she noted worsening with psychological stress. the patient has a family history of mild psoriasis in her mother and grandfather, both well-controlled with topical therapy alone. she was initially treated with clobetasol, cyclosporine, and methotrexate with little improvement. she was then treated with efalizumab, which led to nearly complete resolution of her condition until the drug was taken off the market in 2009.4 after discontinuing efalizumab, she developed new psoriasiform plaques on the feet, hands abstract psoriasis is a common immune-mediated disease that can affect the skin, nails, and joints. management is usually comprised of topical therapy and/or systemic therapy, either biologic or nonbiologic. this case shows a psoriasiform dermatitis with primary response failure to several systemic biologic and nonbiologic therapies for atopic dermatitis (methotrexate, dupilumab) and psoriasis (cyclosporine, adalimumab, ustekinumab, guselkumab, ixekizumab). ultimately, the patient was treated successfully with apremilast. this case suggests that certain cases of psoriasis may improve exclusively with pde-4 inhibition. conversely, this could also suggest existence of a separate entity of psoriasiform dermatitis that is primarily mediated by pde-4. we encourage a trial of apremilast in patients presenting with disease mimicking psoriasis who fail multiple therapies. introduction case report skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 694 figure 1. a) on the bilateral dorsal feet there are large pink erythematous plaques with abundant silvery scale b) after 8 weeks on apremilast, the patient has almost complete resolution with only faintly pink patches. figure 2. a) (4x h&e) regular acanthosis with thinning of the suprapapillary plates and confluent parakeratosis with a mild perivascular infiltrate and minimal spongiosis consistent with a psoriasiform dermatitis b) (10x h&e) there is confluent parakeratosis with few foci of neutrophilic microabscesses in the stratum corneum with focal areas of hypogranulosis. ectatic superficial vessels in the papillary dermis are seen. no eosinophils are noted. and fingers, elbows, forearms, shins, and upper back, affecting approximately 10% of her total body surface area (bsa) (figure 1). she was placed on humira 40mg every other week without improvement. over the next 4 years, various biologic drugs typically used for psoriasis were trialed, including ustekinumab, guselkumab, and ixekizumab. she had intermittent periods of mild improvement but no meaningful response to any medications. given her lack of response to multiple drugs normally effective in psoriasis and considering her history of asthma, an alternate diagnosis of atopic dermatitis was considered. she was placed on dupilumab for 2 months but still did not show any improvement. a punch biopsy from the dorsal ankle was skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 695 performed in november of 2020 showed confluent parakeratosis with focal neutrophils in the stratum corneum, regular acanthosis with focal loss of the granular layer, and a lymphohistiocytic perivascular infiltrate, most consistent with psoriasiform dermatitis (figure 2). there was no t-cell clonality. in january of 2021, the patient started apremilast 60mg per day. within 4 weeks, she noted significant improvement in the thickness and redness of her plaques. she also reported drastic improvement in pruritis and overall appearance, which she had never experienced with any previous medications. after 8 weeks she had near complete clearance (figure 1). apremilast has been demonstrated to be an effective treatment for both psoriasis5 and atopic dermatitis.6 we report a case of a psoriasiform dermatitis refractory to several systemic therapies for atopic dermatitis (methotrexate and dupilumab) and several systemic and biologic therapies for psoriasis (cyclosporine, adalimumab, ustekinumab, guselkumab, and ixekizumab), which ultimately cleared with apremilast. of note, the patient reported clearance on efalizumab but had to stop therapy when it was discontinued from the market. while apremilast has shown to be effective in patients with moderate-to-severe psoriasis who have received prior systemic therapy (conventional and/or biologic),7,8 it is still highly unusual for psoriasis to show primary response failure to this extensive degree of topical and biologic therapies. given our patient’s rapid and profound response to apremilast, we believe that this case suggests that certain cases of psoriasis may improve exclusively with pde4 inhibition. conversely, this could also suggest existence of a separate entity of psoriasiform dermatitis that is primarily mediated by pde-4. we therefore encourage a trial of apremilast in patients presenting with disease mimicking psoriasis who fail multiple therapies. conflict of interest disclosures: none funding: none corresponding author: christopher s. yang, ba department of dermatology northwestern university feinberg school of medicine 676 n. st clair st., suite 1600 chicago, il 60611 phone: 312-695-8106 fax: 312-695-0007 email: christopher.yang@northwestern.edu references: 1. boehncke wh, schon mp. psoriasis. lancet. 2015;386(9997):983-994. 2. armstrong aw, read c. pathophysiology, clinical presentation, and treatment of psoriasis: a review. jama. 2020;323(19):1945-1960. 3. kim wb, jerome d, yeung j. diagnosis and management of psoriasis. can fam physician. 2017;63(4):278-285. 4. talamonti m, spallone g, di stefani a, costanzo a, chimenti s. efalizumab. expert opin drug saf. 2011;10(2):239-251. 5. keating gm. apremilast: a review in psoriasis and psoriatic arthritis. drugs. 2017;77(4):459-472. 6. simpson el, imafuku s, poulin y, et al. a phase 2 randomized trial of apremilast in patients with atopic dermatitis. j invest dermatol. 2019;139(5):1063-1072. 7. paul c, cather j, gooderham m, et al. efficacy and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in patients with moderate-to-severe plaque psoriasis over 52 weeks: a phase iii, randomized discussion conclusion mailto:christopher.yang@northwestern.edu skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 696 controlled trial (esteem 2). br j dermatol. 2015;173(6):1387-1399. 8. papp k, reich k, leonardi cl, et al. apremilast, an oral phosphodiesterase 4 (pde4) inhibitor, in patients with moderate to severe plaque psoriasis: results of a phase iii, randomized, controlled trial (efficacy and safety trial evaluating the effects of apremilast in psoriasis [esteem] 1). j am acad dermatol. 2015;73(1):37-49. skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 250 original research the effect of offering pneumococcal vaccines during specialty care on vaccination rates in patients receiving immunosuppressive therapy joshua lindsley1, nathaniel webb, mph2, ashleigh workman, do3, thaddeus miller, drph, mph2, erica stockbridge, phd1, jean charles, do3, michael carletti, do1,3, stephanie casperson rn, bsn, 4, stephen weis, do1,3,4 1texas college of osteopathic medicine, university of north texas health science center, fort worth, tx 2department of health behavior & health systems, school of public health, university of north texas health science center, fort worth, tx 3department of dermatology, medical city weatherford, weatherford, tx 4john peter smith hospital, jps health network, fort worth, tx abstract purpose: to determine whether clinician-led immunization education with immediate onsite vaccination availability will increase pneumococcal immunizations during specialty care. methods: we used a controlled before and after quasi-experimental design to retrospectively evaluate quality improvement (qi) project effectiveness. the project included two clinics. clinic #1 was a part of the county hospital system and offered comprehensive care. clinic #2 was a university clinic that hosted a private practice and a dermatology resident continuity clinic. resident continuity clinics are structured to enable residents to develop longitudinal relationships with patients with skin disease. patients within each of these clinics were subject to the intervention or usual care based on their treating physician. the intervention included clinician-provided verbal immunization recommendations, dialogue exploring and addressing patients’ immunization concerns, and immediate availability of vaccine and administration. the main measure of outcome was pneumococcal immunization status after qi intervention. results: our analysis included 201 patients with planned or existing immunosuppressive medication regimens attending an initial or follow-up dermatology visit (aged 0-64 years [82.1%], aged ≥65 years [17.9%]; male [34.3%], female [65.6%%]). of these, 146 [72.6%] were in the qi group and 55 [27.4%] in the comparison group. while we identified no significant qi/comparison group differences in immunization status at initial observation (p=0.329), immunization status differed significantly by group at the final observation (p<0.001). the qi group had a significant increase in immunization status compared to the comparison group (p<0.001). overall, 81.4% (95% ci: 73.6, 87.3) of patients in the qi group without full immunization at initial observation received at least one vaccination by the final observation, while we observed no change in immunization status for the comparison group from initial to final observation. conclusion: these data demonstrate that immunization coverage in patients on immunosuppressive medications can be markedly improved by clinician recommendation with immediate availability of the pneumococcal vaccine during specialty care. wider adoption of this model and its adaptation to other immunizations and settings is an important opportunity to reduce vaccine-preventable illness, including covid-19, and improve population health. skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 251 morbidity and mortality from vaccinepreventable illnesses are higher among patients on immunosuppressive treatment.17 immunosuppressive therapies increase the risk of infections by at least 2-fold compared to non-immunosuppressed individuals.6,8 the incidence rate of invasive pneumococcal disease is approximately 6fold higher in patients with chronic inflammatory disease receiving immunosuppressive medications when compared to healthy individuals.9 patients receiving immunosuppressive medications are recommended to receive routine pneumococcal immunizations to reduce infectious complications.10,11 these recommendations are not completely implemented worldwide. studies conducted around the world find that persons on immunosuppressive medications and persons with chronic conditions commonly treated with such medications are undervaccinated, with pneumococcal vaccination rates ranging from 0% in morocco to 56.5% in france.12-15 more effectively addressing this disparity is key to reducing morbidity, mortality, and economic losses from vaccine-preventable disease. 6,12,16,17 there are many reasons vaccination coverage is low in adult and immunosuppressed populations.18-20 most immunosuppressed patients cited lack of physician recommendation for the reason for their being unimmunized.18,21,22 other concerns include vaccine safety and efficacy.20 the most common reason cited by physicians for not immunizing was forgetting to recommend.19,20 another clinician barrier to immunizing is uncertainty of vaccination schedule.18 in addition to patient and clinician barriers there are system immunization barriers including fragmented delivery systems, uneven access, and lack of immunization coordination. vaccination is widely available from pharmacies, urgent care, primary care, specialty, and public health clinics. there is no system for routine communication between these sites providing immunizations and an adult vaccine registry. this can lead to both patient and clinician uncertainty as to an individual’s vaccine status. often as a result of this uncertainty, a patient leaves the office without immunization but with plans for future immunization. recommendations for where vaccination should occur are either absent or it is recommended that they be given by a primary care clinician.23-25 general practitioners surveyed about who should provide immunizations for patients on immunosuppressive medications believed the prescribing specialist should monitor the immunizations.26 surveys of irish rheumatologists showed 57% thought general practitioners should be responsible for providing these patients with immunizations.27 these data illustrate there is discordance about who should ultimately be responsible for vaccinating immunosuppressed patients. the cdc advisory committee on immunization practices (acip) has recommended several strategies to increase vaccine adherence.28 useful methods include direct patient communications and organizational changes such as separate clinics devoted to prevention, planned preventive medicine visits, or the use of nonphysician staff to do preventative medicine visits.29,30 absent or weak immunization recommendations from clinicians are a primary cause of low immunization uptake.31 introduction skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 252 similar to other organizations, our dermatology practice observed low pneumococcal immunization coverage among patients receiving immunosuppressive care. the acip states that the two most important predictors of immunization acceptance among adults are the healthcare provider’s recommendation and availability of the vaccine during the same visit.32 we designed a quality improvement (qi) project around this logic, hypothesizing that clinician-led immunization education with immediate onsite vaccination availability will increase receipt of pneumococcal immunizations during specialty care. we evaluated the results of the qi project and present our findings in this report. this project was approved as exempt category research by the north texas regional institutional review board. study design and participants we used a before and after quasiexperimental design to retrospectively evaluate our qi project to increase acceptance of pneumococcal immunizations in immunosuppressed patients33. our evaluation included all patients who were newly or previously prescribed chronic systemic immunosuppressive therapy that visited any of four dermatology practices during a defined period. therapies of interest included biologics, antimetabolites, oral corticosteroids, and other immunosuppressive medications. the four dermatology practices were in two clinics; one dermatology practice in each clinic administered the qi intervention while the other practice provided standard care. patients were subject to the intervention or usual care based on their treating physician (emethods). all eligible patients seeking care between september (clinic #1) or november (clinic # 2) of 2019 through march 30, 2020 were included in analyses. all were followed for immunization completion through july 2020. both clinics provide care to patients of predominately lower socioeconomic status in tarrant county, texas. in 2019, tarrant county’s estimated population was 2,102,515 residents across its 863.6 square miles; 51.8% of whom were white, 26.7% hispanic or latino, 14.5% black or african american, 4.6% asian, and 2.4% other 34. standard care prior to the qi intervention, pvc13 and ppsv23 pneumococcal vaccine was on the formulary of both institutions and clinic staff were familiar with vaccine administration and emr documentation. however, dermatologists recommended that immunosuppressed patients see their primary clinicians to update pneumococcal vaccinations. quality improvement intervention as a qi intervention, the physician provided each eligible patient with immunization recommendations based on their immunization status and acip guidelines. educational elements included the increased risk of infection associated with immunosuppressive medications, benefits of immunization to reduce this risk, and addressing any concerns the patients had about the vaccine28. patients were given an opportunity to receive pneumococcal immunizations immediately after the physician education. data source and measures data for all variables were retrospectively collected from electronic medical records methods skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 253 (emr). patients were also queried about immunizations received from outside the practice, either during routine visits or in follow-up telephone calls. the primary outcome measure was immunization status. we created a threelevel ordinal immunization status variable based on acip guidelines28, categorizing patients as having no, partial, or full immunization. immunization status was evaluated at two points in time: 1) the first visit to the dermatology clinic during the project period (initial observation), and 2) the end of the observation period (final observation). data from the two clinics were combined for analysis, so patients were in one of two groups: 1) the qi group, or 2) the comparison group. thus, time and group were variables in our analyses. analyses included demographic, care delivery, and patient health variables. demographic variables included gender, age, race/ethnicity. the care delivery variables included insurance status, use of translators, and past-year office-based healthcare visits to any clinician. patient health variables included the number of comorbid conditions, the condition for which immunosuppressive medications were prescribed, the number and types of immunosuppressive medications used, and the number of pneumococcal vaccination indications other than medications and age. statistical analyses we analyzed differences between the qi and comparison groups in demographics, care delivery, health, or immunization status at initial observation. we calculated the unadjusted percentage of patients at each immunization level within each group at initial and final observation. we then used unadjusted and adjusted ordered logit difference-in-difference models to test for significant changes in immunization levels for the two groups. the unadjusted model included group, time, and group by time interaction. the adjusted model added gender, age, insurance, a count of prior year office-based visits, visit type, and the number of indications for vaccination. models accounted for non-independence of initial and final observations. the adjusted model was used to generate the average adjusted probabilities of persons in the qi and comparison group being at each level of immunization at initial and final observations (emethods). additional analyses included an examination of associations between immunization levels at initial observation and the presence and duration of immunosuppressive medication use prior to initial observation. we also analyzed data for the subset of patients who were newly prescribed immunosuppressive medication during the project to evaluate the effectiveness of the intervention on this group. last, we conducted analyses that included only persons in the qi group who were not fully immunized at initial observation to identify factors associated with non-receipt of a vaccination in this group (emethods). all statistical testing was two-sided and used stata 14.2 [statacorp; college station, tx]. significance was tested at p<0.05. our analysis included 201 patients with planned or existing immunosuppression attending an initial or follow-up dermatology visit. of these, 146 (72.6%; 91 from clinic #1 and 55 from clinic #2) were in the qi group and 55 (27.4%; 41 from clinic #1 and 14 from clinic #2) in the comparison group. while the comparison group contained a results skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 254 table 1. characteristics of immunosuppressed patients included in analyses, total and by quality improvement (qi) versus comparison group. variable categories total n=201 column % (95% ci) qi group n=146 column % (95% ci) comparison group n=55 column % (95% ci) p-valuea pneumococcal immunization status at initial observation no immunization 67.2 (60.3, 73.4) 69.9 (61.9, 76.8) 60.0 (46.4, 72.2) 0.329 partially immunized 22.4 (17.1, 28.7) 18.5 (13.0, 25.7) 32.7 (21.5, 46.3) fully immunized 10.5 (6.9, 15.5) 11.6 (7.3, 18.0) 7.3 (2.7, 18.1) gender female 65.6 (58.8, 72.0) 66.4 (58.3, 73.7) 63.6 (50.0, 75.4) 0.709 male 34.3 (28.0, 41.2) 33.6 (26.3, 41.7) 36.4 (24.6, 50.0) age <=34 17.9 (13.2, 23.9) 19.9 (14.1, 27.2) 12.7 (6.1, 24.6) 0.307 35-44 17.9 (13.2, 23.9) 19.9 (14.1, 27.2) 12.7 (6.1, 24.6) 45-54 20.9 (15.8, 27.1) 17.8 (12.4, 24.9) 29.1 (18.5, 42.6) 55-64 25.4 (19.8, 31.9) 24.7 (18.3, 32.4) 27.3 (17.0, 40.7) >=65 17.9 (13.2, 23.9) 17.8 (12.4, 24.9) 18.2 (10.0, 30.8) race/ethnicity white non-hispanic 37.8 (31.3, 44.8) 40.4 (32.7, 48.6) 30.9 (20.0, 44.4) 0.162 black non-hispanic 23.9 (18.4, 30.3) 19.9 (14.1, 27.2) 34.5 (23.1, 48.1) hispanic 31.8 (25.7, 38.7) 33.6 (26.3, 41.7) 27.3 (17.0, 40.7) other race/ethnicity 6.5 (3.8, 10.9) 6.2 (3.2, 11.5) 7.3 (2.7, 18.1) primary insurance private 11 (7.3, 16.1) 11.6 (7.3, 18.0) 9.1 (3.8, 20.3) 0.176 public (medicare or medicaid) 52.2 (45.3, 59.1) 56.2 (47.9, 64.1) 41.8 (29.4, 55.3) county program 26.9 (21.1, 33.5) 23.3 (17.1, 30.9) 36.4 (24.6, 50.0) uninsured 10 (6.5, 15.0) 8.9 (5.2, 14.8) 12.7 (6.1, 24.6) patient used translatorb yes 19.9 (13.2, 23.9) 17.8 (12.4, 24.9) 18.2 (10.0, 30.8) 0.951 count of past year office-based contacts (all provider specialties) 0-3 visits 23.4 (18.0, 29.8) 28.1 (21.3, 36.0) 10.9 (4.9, 22.5) 0.068 4-8 visits 31.3 (25.3, 38.1) 29.5 (22.6, 37.4) 36.4 (24.6, 50.0) 9-14 visits 27.4 (21.6, 34.0) 26.7 (20.1, 34.5) 29.1 (18.5, 42.6) >=15 visits 17.9 (13.2, 23.9) 15.8 (10.7, 22.7) 23.6 (14.1, 36.8) visit type at initial observation initial 23.4 (18.0, 29.8) 19.2 (13.5, 26.5) 34.5 (23.1, 48.1) 0.022 follow-up 76.6 (70.2, 82.0) 80.8 (73.5, 86.5) 65.5 (51.9, 76.9) number of comorbid conditionsb none 14.4 (10.2, 20.0) 15.1 (10.1, 21.9) 12.7 (6.2, 24.5) 0.681 1-3 conditions 47.8 (40.9, 54.7) 48.6 (40.6, 56.8) 45.5 (32.8, 58.7) 4 or more conditions 37.8 (31.3, 44.8) 36.3 (28.9, 44.4) 41.8 (29.5, 55.2) immunosuppressive medications used prior to initial observationc yes 83.1 (77.2, 87.7) 83.6 (76.6, 88.8) 81.8 (69.2, 90.0) 0.769 condition for which individual was prescribed immunosuppressive medication(s) (all provider specialties) psoriasis with or without psoriatic arthritis 70.2 (63.4, 76.1) 69.2 (61.1, 76.2) 72.7 (59.3, 83.0) 0.474 hidradenitis suppurativa 9.5 (6.1, 14.4) 9.6 (5.7, 15.6) 9.1 (3.8, 20.3) connective tissue disease 8.5 (5.3, 13.2) 9.6 (5.7, 15.6) 5.5 (1.7, 15.8) rheumatoid arthritis 5.5 (3.0, 9.7) 4.8 (2.3, 9.8) 7.3 (2.7, 18.1) vesiculobullous disease 4 (2.0, 7.8) 4.8 (2.3, 9.8) 1.8 (0.2, 12.1) skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 255 atopic dermatitis 1 (0.2, 3.9) 0.7 (0.1, 4.8) 1.8 (0.2, 12.1) inflammatory bowel disease 0.5 (0.1, 3.5) 0.7 (0.1, 4.8) 0 chronic lichenoid inflammatory disease 0.5 (0.1, 3.5) 0.7 (0.1, 4.8) 0 organ transplant 0.5 (0.1, 3.5) 0 1.8 (0.2, 12.1) current number of immunosuppressive medications prescribed (all provider specialties) 1 medication 80.6 (74.5, 85.5) 80.1 (72.8, 85.9) 81.8 (69.2, 90.0) 0.788 2 medications 17.4 (12.7, 23.3) 17.8 (12.4, 24.9) 16.4 (8.7, 28.8) 3 medications 2 (0.7, 5.2) 2.1 (0.7, 6.2) 1.8 (0.2, 12.1) prescribed biologicsd yes 80.1 (73.9, 85.1) 82.2 (75.1, 87.6) 74.5 (61.3, 84.4) 0.226 prescribed antimetabolites, corticosteroids, or other immunosuppressived yes 31.3 (25.3, 38.1) 30.8 (23.8, 38.8) 32.7 (21.6, 46.1) 0.795 number of indications for immunization other than medication(s) and aged 0 indications 45.3 (38.5, 52.2) 44.5 (36.6, 52.7) 47.3 (34.4, 60.5) 0.765 1 indication 32.8 (26.6, 39.7) 33.6 (26.3, 41.7) 30.9 (20.0, 44.4) 2 indications 14.9 (10.6, 20.6) 14.4 (9.5, 21.1) 16.4 (8.7, 28.8) 3 indications 6 (3.4, 10.3) 6.9 (3.7, 12.3) 3.6 (0.9, 13.7) 4 indications 1 (0.2, 3.9) 0.7 (0.1, 4.8) 1.8 (0.2, 12.1) a significance was evaluated using pearson’s chi-squared tests and wilcoxon rank-sum tests for categorical and ordinal variables, respectively. b comorbid conditions included asthma, cad, cancer, chronic pain, copd, chronic renal failure, diabetes, high cholesterol, hypertension, hypothyroidism, psychiatric, seizures gerd, oaa, or other conditions. c dichotomous yes/no variables only display data for the "yes" category. d indications include heart disease (chf or cad), diabetes, lung disease (copd or asthma), chronic renal failure, or being a current smoker. possible range 0-5, actual range 0-4 table 2. unadjusted and adjusted column percentages reflecting immunization status by group and point in time. n=201. qi group (n=146) comparison group (n=55) pvalue qi group (n=146) comparison group (n=55) pvalue unadjusted column percentages (95% ci) adjusted column percentagesa (95% ci) immunization status initial observation final observation initial observation final observation initial observation final observation initial observation final observation no immunization 69.9 (61.9, 76.8) 13.7 (9.0, 20.4) 60.0 (46.4, 72.2) 60.0 (46.4, 72.2) <0.001 66.3 (59.8, 72.7) 16.1 (10.9, 21.3) 62.1 (53.6, 71.6) 62.1 (53.6, 71.6) <0.001 partially immunized 18.5 (13.0, 25.7) 47.9 (39.9, 56.1) 32.7 (21.5, 46.3) 32.7 (21.5, 46.3) 26.1 (21.3, 30.9) 43.2 (37.0, 49.4) 28.7 (21.4, 36.0) 28.7 (21.4, 36.0) fully immunized 11.6 (7.3, 18.0) 38.4 (30.8, 46.6) 7.3 (2.7, 18.1) 7.3 (2.7, 18.1) 7.7 (3.9, 11.4) 40.6 (0.34, 0.47) 9.2 (5.0, 13.4) 9.2 (5.0, 13.4) a adjusted column percentages are the average predicted probabilities calculated based on results of a multivariable ordered logit model (see table 4 in the supplement); probabilities multiplied by 100 and expressed as percentages skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 256 higher proportion of new patients (p-value = 0.022), we found no significant differences between qi and comparison groups for other demographic, care delivery, or health variables (p>0.05 for each; table 1). while our unadjusted analyses identified no significant group differences in immunization status at initial observation (p=0.329; table 1), immunization status differed significantly by qi/comparison group at the final observation (p<0.001; table 2). of the 102 patients in the qi group with no pneumococcal immunizations at initial observation, 80.4% (95% ci: 71.4%, 87.1%) received at least one pneumonia vaccination by the final observation. for the 27 patients in the qi group with partial immunization at project initiation, 85.2% (95% ci: 65.9%, 94.5%) received at least one pneumonia vaccination. overall, 81.4% (95% ci: 73.6, 87.3) of patients in the qi group without full immunization at initial observation received at least one vaccination by the final observation. pneumococcal immunization statuses did not change during the project period within the comparison group (table 2). regression analyses identified that the qi group had a significant change in immunization status compared to the comparison group (table 2; unadjusted difference-in-difference p<0.001, table 3). immunization acceptance patterns for the subset of 34 patients not previously on immunosuppression who were prescribed immunosuppressive medication during the project were similar. of those with new prescriptions, 75% (18/24; 95% ci: 53.0, 88.9) of the qi group and 0% (0/10) of the comparison group received at least one pneumococcal immunization by final observation (p<0.001; data not shown). table 3: results of unadjusted ordered logit model examining differences in immunization status for the qi group versus comparison group at initial versus final observation. analysis accounts for repeated measures (n=201). odds ratio (or) 95% confidence interval of or p-value group comparison group 1.00 (ref) qi group 0.72 0.38 1.37 0.321 time initial observation 1.00 (ref) final observation 1.00 . . . interaction group*time 10.14 6.71 15.34 <0.001 findings were similar after adjusting for demographic, clinical, and other factors, with a significant change in immunization status at final observation among patients in the qi group and no change in the comparison group (table 2). consequently, there was a significant interaction between group and time (p=<0.001; table 4). figure 1 visualizes the predicted probabilities of persons in the qi group being immunized at initial versus final observation. for the qi group, the predicted probabilities of having no, partial, or full immunizations at initial observation were 0.66, 0.26, and 0.08, respectively. at the time of final observation for the qi group, the predicted probabilities of having no, partial, or full immunizations were 0.16, 0.43, and 0.41, respectively. predicted probabilities for the comparison group of having no, partial, or full immunizations at initial observation were 0.62, 0.29, and 0.09, respectively and did not change during the project (table 2). controlling for time, group, and other factors, patients 65 years of age or older had significantly greater odds of having a higher immunization status compared to skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 257 figure 1. adjusted average predicted probabilities of persons in the qi group being unimmunized, partially immunized, and fully immunized at initial and final observations. probabilities were generated based on the results of the multivariable ordered logit model detailed in etable 2 of the supplement. younger persons (p=<0.001). a significant association was also found between the number of risk factors for pneumonia and higher immunization statuses (p=0.034). conversely, the number of prior office visits was not significantly associated with immunization level after controlling for other factors (table 4; p>0.05 for all levels). our analyses investigating variations in the intervention's effectiveness indicated uninsured patients were less likely to receive a vaccination relative to insured patients (unadjusted p=0.007, adjusted p=0.015; table 5). further, regardless of group, immunosuppressive medication use before initial observation was not significantly associated with immunization status. this was true whether medication use was dichotomized (z=-0.35, p=0.725) or categorized based on immunosuppression duration (r2=0.11, p=0.119; table 6). pneumococcal immunizations are indicated for adults at risk of severe disease, hospitalization, and death from pneumococcal illnesses28. this public health recommendation is incompletely implemented worldwide leaving a large gap discussion skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 258 table 4. results of multivariable ordered logit model. the model's dependent variable is immunization status; the main predictor variables are group, time and the group by time interaction. analysis accounts for repeated measures (n=201). odds ratio (or) 95% confidence interval of or p-value group comparison group 1.00 (ref) qi group 0.77 0.38 1.59 0.485 time initial observation 1.00 (ref) final observation 1.00 . . . interaction group*time 19.12 11.53 31.72 <0.001 gender female 1.00 (ref) male 1.24 0.68 2.27 0.479 age <=34 1.00 (ref) 35-44 0.65 0.26 1.61 0.353 45-54 0.87 0.39 1.95 0.739 55-64 1.18 0.50 2.82 0.703 >=65 17.64 5.51 56.48 <0.001 insurance private 1.00 (ref) public (medicare or medicaid) 1.34 0.44 4.08 0.604 county program 1.58 0.55 4.53 0.393 uninsured 0.34 0.08 1.43 0.141 count of prior office-based contacts (all provider specialties) 0-3 visits 1.00 (ref) 4-8 visits 0.86 0.39 1.91 0.718 9-14 visits 1.16 0.51 2.67 0.720 >=15 visits 1.78 0.71 4.45 0.216 visit type at project initiation initial 1.00 (ref) follow-up 1.01 0.49 2.10 0.979 number of risk factors other than medication(s) and agea count variable 1.46 1.03 2.08 0.034 a includes heart disease (congestive heart failure or coronary artery disease), diabetes, lung disease (chronic obstructive pulmonary disease or asthma), chronic renal failure, or being a current smoker. possible range 0-5, actual range 0-4. in vaccine coverage and many individuals at risk for preventable health loss 12-15. we implemented a qi project incorporating patient education with the opportunity for immediate immunization for patients prescribed new or existing immunosuppressive therapies in a specialty care clinic. we found 81% (105 of 129) of patients with incomplete pneumococcal immunization accepted immediate vaccination. these data demonstrate that immunization coverage in patients on immunosuppressive medications can be markedly improved by direct physician recommendation with convenient, immediate availability of the pneumococcal vaccine during specialty care. the acip guidelines for pneumococcal immunization are complex. there are two nonequivalent pneumococcal vaccines, pcv-13 and ppsv23 with indications by age, specific illnesses, lifestyle behaviors, sequence of administration, and broad categories of risk including immunocompromise 35. recommendations are for single and in other scenarios for both vaccines. in circumstances where both vaccines are recommended, a specific sequence is recommended, with pcv-13 initially then ppsv23 given 8 weeks later. patients in the qi program were likely immunized for other indications. we found patients were more likely to be vaccinated if they were over 65 or had other indications for pneumococcal immunization (table 4). the emr system of both institutions has an automatic care-gap function to remind clinicians of recommended practices compared to current care. currently, both sites include age 65 or older as the only trigger for care-gap pneumococcal immunization reminder. the emr was therefore an immunization barrier at both institutions. improved emr programming could improve reminders for pneumococcal skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 259 immunizations, improve care-gap recognition, and potentially improve immunization uptake. table 5. results of logistic regression model examining adjusted associations between receipt of one or more pneumonia vaccinations during the qi project and patient characteristics. includes persons in the qi group who were not already fully immunized at initial observation (n=129). odds ratio (or) 95% confidence interval of or pvalue gender female 1.00 (ref) male 1.06 0.35 3.24 0.917 age <=34 1.00 (ref) 35-44 0.81 0.20 3.37 0.777 45-54 3.79 0.56 25.67 0.172 55-64 1.40 0.26 7.64 0.699 >=65 1.06 0.15 7.50 0.955 insurance private 1.00 (ref) public (medicare or medicaid) 0.89 0.15 5.22 0.893 county program 1.10 0.15 8.06 0.927 uninsured 0.07 0.01 0.59 0.015 patient used translator yes 1.00 (ref) no 7.14 0.91 56.31 0.062 count of prior officebased contacts (all provider specialties) 0-3 visits 1.00 (ref) 4-8 visits 0.62 0.17 2.28 0.473 9-14 visits 0.85 0.20 3.68 0.829 >=15 visits 0.74 0.14 3.82 0.717 visit type at project initiation initial 1.00 (ref) follow-up 1.98 0.52 7.51 0.317 number of indications other than medication(s) and agea count variable 0.98 0.50 1.91 0.952 immunosuppressive medications used prior to initial observation no 1.00 (ref) yes 0.40 0.08 2.06 0.271 a includes heart disease (congestive heart failure or coronary artery disease), diabetes, lung disease (chronic obstructive pulmonary disease or asthma), chronic renal failure, or being a current smoker. possible range 0-5, actual range 0-4 other systematic barriers to optimal immunization include ambiguity around who is responsible for vaccination. patients with multiple specialty healthcare system contacts may have fewer primary care immunization opportunities36. the official position of the acip is that every healthcare provider has a fundamental responsibility for ensuring patients are current with immunizations. the national psoriasis foundation recommends that dermatologists give immunization education but vaccination should be by primary care clinicians 23. another systems barrier is incomplete communication between multiple providers. patients, especially those with chronic health problems, may require care from multiple specialists as well as primary care providers, and a patient's immunization history can be uncertain, inaccurate, or imperfectly shared between these locations 36,37. we evaluated such barriers in our local context. since every clinician could act as a potential immunizer, we sought to identify whether the frequency and type of outpatient visits over time impacted immunization status at first observation. we identified office-based visits with primary, dermatological, and other specialty providers for all patients during the 12 months prior to first observation. we found that the number of prior office visits was not significantly associated with immunization level after controlling for other factors (table 4). this demonstrates "diffusion of responsibility" or a situation where if everyone is responsible for immunizations, no one is responsible. one solution would be for the acip to define which provider is responsible for certain immunizations more precisely. the indication for immunization could direct consensus to standardize accountability. in this regard, the provider created indications could be managed by the prescribing provider. at the same time, skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 260 table 6. association between immunization status at initial observation and prior immunosuppressive use. immunization status at initial observation total n=201 % (95% ci) used immunosuppressive medications prior to initial observation % (95% ci) time on immunosuppressive medications prior to initial observation % (95% ci) no n=34 yes n=167 pvalue none: new user n=34 <1 year n=36 1 to <3 years n=48 3 to <6 years n=33 ≥6 years n=50 pvalue no immunization 67.2 (60.3, 73.4) 70.6 (53.0, 83.6) 66.5 (58.9, 73.3) 0.725 70.6 (53.0, 83.6) 77.8 (61.1, 88.6) 70.8 (56.3, 82.1) 57.6 (40.1, 73.3) 60.0 (45.8, 72.7) 0.119 partially immunized 22.4 (17.1, 28.7) 17.6 (8.0, 34.5) 23.3 (17.5, 30.4) 17.6 (8.0, 34.5) 8.3 (2.6, 23.3) 25.0 (14.6, 39.3) 30.3 (16.9, 48.1) 28.0 (17.2, 42.1) fully immunized 10.5 (6.9, 15.5) 11.8 (4.4, 27.9) 10.2 (6.4, 15.8) 11.8 (4.4, 27.9) 13.9 (5.8, 29.7) 4.2 (1.0, 15.5) 12.1 (4.5, 28.6) 12.0 (5.4, 24.5) routine immunizations may be best done by primary care clinicians. the cost of care affects adherence to health care immunization recommendations38,39. a 2012 national health interview survey showed pneumococcal coverage of adults at high-risk for pneumococcal pneumonia was 9.8% versus 23.0% in underinsured patients vs. insured patients 40. in our qi project, we also identified cost as a barrier to immunization. uninsured patients were the only group in which the qi intervention was not successful (unadjusted p=0.007, adjusted p=0.015; table 5). in pediatric populations, the vaccine for children program covers vaccine costs for children unable to pay41. a similar public program for adults could reduce vaccine disparities and increase uninsured patients' opportunities to be immunized. immunosuppression attenuates the immunological response to vaccination, and ideally, patients complete their immunizations before starting immunosuppressive therapies42. in this qi project where immunizations were immediately available as part of the process of initiating immunosuppressive treatment, 75% of those in the qi group (18/24; 95% ci: 53.0, 88.9) and 0% in the comparison group (0/10) received at least one pneumococcal vaccination before starting immunosuppression. our results suggest that one potential method to improve immunization coverage of patients preparing to initiate immunosuppressive medications would be to have immunizations immediately available for administration as part of the immunosuppressant preparation process. there have been mixed results from quality improvement and other initiatives to increase immunization coverage43-47. ineffective strategies included patient education by nursing, point-of-care paper worksheets with questionnaires, and letters to patients 31. successful strategies have included designating non-physician staff responsible for vaccine administration, designated clinics for preventive care, standing orders, and email reminders or prompts to providers29,30,48-50. the most effective strategies have been system-level interventions. these included electronic reminders with linked order sets, physician auditing and feedback, patient outreach, and printed prescriptions. prior research examining the impact of these strategies found that the receipt rate for any pneumococcal immunization increased 160%, from roughly 29% to 46%49. our qi approach of physician recommendation with convenient, immediate availability of the skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 261 pneumococcal vaccine during specialty care had 1.5 times this impact -the predicted probability for an immune suppressed patient to have received one or more immunizations against pneumococcal pneumonia rose 247% in the presence of our intervention, from 34% to 84%. given our experience it is likely this method could improve care if it were adopted by others. there are several limitations to our analyses. first, our data are geographically and demographically narrow, representing the experience of two dermatology practices in north-central texas primarily serving patient populations eligible for subsidized medical care. our patient population may therefore not represent the overall patient population on immunosuppressive medications. second, the study was retrospective in design, and data may have been missed or not collected. this may impact some areas of the study's power. third, although patients from two clinics were included in analyses, small sample sizes precluded us from statistically adjusting for the multi-site nature of the data51. larger sample sizes of patients seen in a greater number of specialty practices by a larger number of clinicians are needed to replicate our findings and solidify intervention effect estimates. we analyzed the combined effect of physician recommendation, patient education, and the immediate availability of immunizations. as a result, we cannot determine the extent to which each intervention resulted in increased vaccine uptake. we observed, then successfully addressed, a substantial gap between recommended pneumococcal immunization in immunosuppressed patients and actual immunization coverage among adult patients receiving specialist dermatology care. a dual strategy of direct patient education by the treating physician with immediate availability of vaccine and administration resulted in 81% of these highrisk patients obtaining full or partial pneumococcal immunization, a 247% increase in the predicted probability of full or partial immunity over baseline. wider adoption of this model and its adaptation to other immunizations and settings is an important opportunity to reduce vaccinepreventable illness, including covid-19, and improve population health. acknowledgements: we would like to acknowledge jps health network and university of north texas health science center for the continued emphasis on safe, high quality patient care, and support of this quality improvement initiative. conflict of interest disclosures: none funding: none corresponding author: dr. stephen weis stephen weis, do the university of north texas health science center at fort worth department of dermatology 855 montgomery st fort worth, tx 76107 phone 817-735-0278 email stephen.weis@unthsc.edu references: 1. zabana y, rodríguez l, lobatón t, et al. relevant infections in inflammatory bowel disease, and their relationship with immunosuppressive therapy and their effects on disease mortality. journal of crohn's and colitis. 2019;13(7):828-837. 2. toruner m, loftus ev, harmsen ws, et al. risk factors for opportunistic infections in patients with inflammatory bowel disease. gastroenterology. 2008;134(4):929-936. 3. radovits bj, fransen j, al shamma s, eijsbouts am, van riel plcm, laan rfjm. excess mortality emerges after 10 years in an inception conclusion mailto:stephen.weis@unthsc.edu skin may 2021 volume 5 issue 3 copyright 2021 the national society for 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voorhees as. from the medical board of the national psoriasis foundation: vaccination in adult patients on systemic therapy for psoriasis. journal of the american academy of dermatology. 2013;69(6):1003-1013. 24. furer v, rondaan c, heijstek mw, et al. 2019 update of eular recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases. annals of the rheumatic diseases. 2020;79(1):39. 25. wong pkk, hanrahan p. management of vaccination in rheumatic disease. best practice & research clinical rheumatology. 2018;32(6):720-734. 26. lejri-el euchi h, chirpaz e, foucher a, et al. vaccination against influenza and pneumococcal infections in patients with autoimmune disorders skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 263 under biological therapy: coverage and attitudes in patients and physicians. european journal of internal medicine. 2019;69:25-31. 27. mccarthy em, azeez ma, fitzpatrick fm, donnelly s. knowledge, attitudes, and clinical practice of rheumatologists in vaccination of the at-risk rheumatology patient population. jcr: journal of clinical rheumatology. 2012;18(5). 28. centers for disease c. pneumococcal acip vaccine recommendations. published november 21, 2014. accessed october 9, 2020. 29. szilagyi p, vann j, bordley c, et al. interventions aimed at improving immunization rates. cochrane database syst rev. 2002(4):cd003941. 30. stone eg, morton sc, hulscher me, et al. interventions that increase use of adult immunization and cancer screening services. annals of internal medicine. 2002;136(9):641651. 31. murray k, low c, o’rourke a, et al. a quality improvement intervention failed to significantly increase pneumococcal and influenza vaccination rates in immunosuppressed inflammatory arthritis patients. clinical rheumatology. 2020;39(3):747-754. 32. ventola cl. immunization in the united states: recommendations, barriers, and measures to improve compliance: part 1: childhood vaccinations. p t. 2016;41(7):426-436. 33. reeves bc, wells ga, waddington h. quasiexperimental study designs series-paper 5: a checklist for classifying studies evaluating the effects on health interventions-a taxonomy without labels. j clin epidemiol. 2017;89:30-42. 34. burea usc. u.s. census bureau quickfacts: tarrant county, texas. https://www.census.gov/quickfacts/tarrantcountyt exas. published 2010. accessed. 35. green c, moore c, mahajan a, bajaj k. a simple approach to pneumococcal vaccination in adults. journal of global infectious diseases. 2018;10(3):159-162. 36. doherty m, schmidt-ott r, santos ji, et al. vaccination of special populations: protecting the vulnerable. vaccine. 2016;34(52):6681-6690. 37. dorell cg, jain n, yankey d. validity of parentreported vaccination status for adolescents aged 13-17 years: national immunization surveyteen, 2008. public health rep. 2011;126 suppl 2(suppl 2):60-69. 38. hinman ar, orenstein wa. adult immunization: what can we learn from the childhood immunization program? clinical infectious diseases. 2007;44(12):1532-1535. 39. national vaccine advisory c. recommendations from the national vaccine advisory committee: standards for adult immunization practice. public health rep. 2014;129(2):115-123. 40. lu p-j, o’halloran a, williams ww. impact of health insurance status on vaccination coverage among adult populations. american journal of preventive medicine. 2015;48(6):647661. 41. whitney cg, zhou f, singleton j, schuchat a, centers for disease c, prevention. benefits from immunization during the vaccines for children program era united states, 1994-2013. mmwr morb mortal wkly rep. 2014;63(16):352-355. 42. agarwal n, ollington k, kaneshiro m, frenck r, melmed gy. are immunosuppressive medications associated with decreased responses to routine immunizations? a systematic review. vaccine. 2012;30(8):14131424. 43. shea s, dumouchel w, bahamonde l. a metaanalysis of 16 randomized controlled trials to evaluate computer-based clinical reminder systems for preventive care in the ambulatory setting. j am med inform assoc. 1996;3(6):399409. 44. vann jcj, jacobson rm, coyne‐beasley t, asafu‐adjei jk, szilagyi pg. patient reminder and recall interventions to improve immunization rates. cochrane database of systematic reviews. 2018(1). 45. dexter pr, perkins sm, maharry ks, jones k, mcdonald cj. inpatient computer-based standing orders vs physician reminders to increase influenza and pneumococcal vaccination rates: a randomized trial. jama. 2004;292(19):2366-2371. 46. nichol kl. ten-year durability and success of an organized program to increase influenza and pneumococcal vaccination rates among high-risk adults. the american journal of medicine. 1998;105(5):385-392. 47. briss pa, rodewald le, hinman ar, et al. reviews of evidence regarding interventions to improve vaccination coverage in children, adolescents, and adults11the names and affiliations of the task force members are listed on page v of this supplement and at http://www.thecommunityguide.org22some of this material was published previously in: shefer a, briss p, rodewald l, et al. improving immunization coverage rates: an evidence-based review of the literature. epidemiol rev 1999;20:96–142. american journal of preventive medicine. 2000;18(1, supplement 1):97-140. 48. desai sp, lu b, szent-gyorgyi le, et al. increasing pneumococcal vaccination for https://www.census.gov/quickfacts/tarrantcountytexas https://www.census.gov/quickfacts/tarrantcountytexas http://www.thecommunityguide.org22some/ skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 264 immunosuppressed patients: a cluster quality improvement trial. arthritis & rheumatism. 2013;65(1):39-47. 49. baker dw, brown t, lee jy, et al. a multifaceted intervention to improve influenza, pneumococcal, and herpes zoster vaccination among patients with rheumatoid arthritis. j rheumatol. 2016;43(6):1030-1037. 50. dempsey af, zimet gd. interventions to improve adolescent vaccination: what may work and what still needs to be tested. american journal of preventive medicine. 2015;49(6, supplement 4):s445-s454. 51. feaster dj, mikulich-gilbertson s, brincks am. modeling site effects in the design and analysis of multi-site trials. am j drug alcohol abuse. 2011;37(5):383-391. microsoft powerpoint poster lentigo_20210218 • cysteamine is an aminothiol derived from coenzyme a degradation in mammalian cells and is naturally found in human breast milk.1 serving as intracellular antioxidant, cysteamine has anti-carcinogenic effect.1 • chavin first discovered the potent depigmenting effect of cysteamine in vivo in 1966.2 but its topical use was historically prohibited due to a very offensive odor and rapid oxidation. • scientis developed in 2012 a unique stabilization method that allowed the use of cysteamine topically. • multiple studies have demonstrated the significant efficacy in the treatment of melasma3-8 and pih10, with comparable or better results than hydroquinone5-6, kligman’s formula7-8 and mesotherapy with tranexamic acid.9 • cysteamine has a broad action in the regulation of melanogenesis: o enzymatic effect: inhibition of tyrosinase and peroxidase. o chemical effect: chelation of mineral ions, preventing fenton-type reactions. o antioxidant: lightening of dark melanin in stratum corneum. o cascade reaction: increase of intracellular glutathione, amplifying natural depigmenting effects. what is cysteamine ?what is cysteamine ? • solar lentigines are macules and hyperpigmented patches ranging from a few millimeters to a few centimeters.11 • the prevalence of solar lentigo is associated with aging, in which 90% of white-skinned people over the age of 60 years have these lesions. 12 • in 2008, a study shows the impact on quality of life of lentigo : >40% of 105 us patients with lentigo were embarrassed because of their skin. • topical depigmenting products are usually ineffective for the treatment of lentigines. lentigines are also resistant to triple combination therapy, as indicated by dr kligman.14 why focus on lentigo ?why focus on lentigo ? results with cysteamine 5%results with cysteamine 5% • significant improvement of senile lentigos after 12 weeks • 40% reduction of colorimetry • topical cysteamine (cyspera®) is one of the first monotherapy treatments demonstrating significant efficacy in reduction of dorsal hand lentigines by all evaluation methods. conclusionconclusion 1. besouw, m, and al. (2013). "cysteamine: an old drug with new potential". drug discovery today. 18 (15-16): 785–792. https://doi.org/10.1016/j.drudis.2013.02.003 2. chavin, w.; schlesinger, w. (1966). "some potent melanin depigmentary agents in the black goldfish". die naturwissenschaften 53(16): 413–414. https://doi.org/10.1007/bf00625789 3. mansouri, p and al. (2015)."evaluation of the efficacy of cysteamine 5% cream in the treatment of epidermal melasma: a randomized double-blind placebo-controlled trial". the british journal of dermatology. 173 (1): 209–21. https://doi.org/10.1111/bjd.13424 4. farshi et al. (2018). ”efficacy of cysteamine cream in the treatment of epidermal melasma, evaluating by dermacatch : a randomized double blind placebo controlled study”. j. dermatol. treat. 29:2, 182189. https://doi.org/10.1080/09546634.2017.1351608 5. fitzpatrick and al. (1968). "selective action of mercaptoethylamines on melanocytes in mammalian skin: experimental depigmentation". arch dermatol 97:465–77 10. 6. nguyen et al. (2020). “evaluation of the efficacy of cysteamine cream compared to hydroquinone in the treatment of melasma: a randomised, double-blinded trial” aust. j. dermatol. https://doi.org/10.1111/ajd.13432 7. kasraee et al. (2019). “significant therapeutic response to cysteamine cream in a melasma patient resistant to kligman's formula”. j cosmet dermatol. 18(1):293-295. https://doi.org/10.1111/jocd.12837 8. karrabi et al. (2020). “clinical evaluation of efficacy, safety and tolerability of cysteamine 5% cream in comparison with modified kligman’s formula in subjects”, skin res technol. https://doi.org/10.1111/srt.12901 9. karrabi, and al. (2020). ”clinical evaluation of efficacy and tolerability of cysteamine 5% cream in comparison with tranexamic acid mesotherapy in subjects with melasma: a single-blind, randomized clinical trial study”. arch dermatol res. https://doi.org/10.1007/s00403-020-02133-7 10. mathe, balogun, yoo. (2021). “a case report on the use of topical cysteamine 5% cream in the management of refractory postinflammatory hyperpigmentation (pih) resistant to triple combination cream (hydroquinone, topical corticosteroids, and retinoids)”. j cosmet dermatol. ; 20: 204206. https://doi.org/10.1111/jocd.13755 11. james wd and al. (2011). “andrew’s diseases of the skin e-book: clinical dermatology” elsevier health sciences 12. šitum m and al. (2010). “senile lentigo–cosmetic or medical issue of the elderly population”. collegium antropologicum. 34(2):85-8. 13. taylor a and al. (2008). “prevalence of pigmentary disorders and their impact on quality of life: a prospective cohort study”. j cosmet dermatol. sep;7(3):164-8. https://doi.org/10.1111/j.14732165.2008.00384.x 14. kligman, a. m., & willis, i. (1975). “a new formula for depigmenting human skin. archives of dermatology, 111(1), 40-48. doi:10.1001/archderm.1975.01630130042004 referencesreferences • randomized, double-blinded; 30 subjects with dorsal hand lentigines • cyspera® cysteamine 5% from scientis vs vehicle, 15-minutes daily short contact; sunscreen daily • colorimetry and visual analogue scale (vas) at baseline, 4-weeks, 8-weeks and 12-weeks • mean age 49.5; gender 8:22 m:f distributed equally material & methodsmaterial & methods vehicle cysteamine 0 50 100 150 200 250 300 350 400 450 500 387 294 397 481 colorimetry vehicle cysteamine 0 1 2 3 4 5 6 7 8 9 7.46 5.09 7.33 8.27 vas subject 1 baseline week-12 subject 2 baseline week-12 40% reduction in colorimetry (p<0.002) vs 2% reduction in non-treatment arm (p<0.405) 40% reduction in vas (p<0.001) vs 2% reduction in non-treatment arm p<0.245) learn more about the product: stabilized cysteamine 5% cream for the treatment of senile lentigo nasrin saki, md, shiraz university of medical sciences stabilized cysteamine 5% cream for the treatment of senile lentigo nasrin saki, md, shiraz university of medical sciences skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 183 skinmages an uncommon presentation of erosive pustular dermatosis: a large, crusted plaque on the scalp james mackenzie, ms,1 miriam sagher, fnp-bc,2 ethan sagher, md,2 ben j. friedman, md,2 jesse veenstra, md, phd2 1 wayne state university school of medicine, detroit, mi 2 department of dermatology, henry ford health system, detroit, mi figure 1. a) large crusted plaque on the frontal scalp. b) immediately after complete debridement. c) complete resolution of affected area 6 weeks after debridement and clobetasol 0.05% ointment twice daily for 2 weeks. erosive pustular dermatosis (epd) is an often underrecognized inflammatory condition that typically manifests with small scattered crusted erosions and pustules on the scalp of elderly patients. many patients with epd have concurrent actinic damage and a history of keratinocytic carcinomas, which may confound the diagnosis of epd. recognition of possible manifestations of epd is imperative to ensure appropriate diagnostic workup and subsequent management to avoid non-productive therapy. we present an uncommon, but important to recognize, manifestation of epd as a large solitary crusted plaque on the scalp of an elderly patient, which has been seldom reported. an 83-year-old caucasian male presented with an asymptomatic crusted plaque on the scalp that had been growing over the past 5 years. on physical exam, there was a nontender 8 x 8 cm thick crusted plaque overlying the frontal scalp (fig 1a) without adjacent lesions. there was no palpable auricular or cervical lymphadenopathy present. the posterior section of the crust was removed with a scalpel to uncover an skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 184 area of underlying friable, ulcerated tissue and purulent exudate where a wound culture and tangential shave biopsy were performed. histopathology revealed a dense dermal infiltrate composed of lymphocytes, plasma cells, and neutrophils (fig 2). bacterial culture grew pan-sensitive figure 2. lowand high-power magnification of shave biopsy showing ulceration with a dense dermal infiltrate composed of lymphocytes, plasma cells, and neutrophils (hematoxylin & eosin) staphylococcus aureus, which was treated with doxycycline 100 mg twice daily for 14 days. clinicopathological correlation led to a diagnosis of epd (plaque type), and the patient underwent complete debridement of the crusted plaque revealing ulceration (fig 1b). the patient was started on clobetasol 0.05% ointment twice daily to the ulcerated portion of the lesion with complete resolution after several weeks of use, as reepithelization was noted when he returned to the clinic 6 weeks after debridement (fig 1c). no recurrence was observed after 6 months. rarely, large solitary crusted plaques may be the sole manifestation of epd, but have been seldom described in the current literature.1 the true prevalence and incidence of epd are not well characterized but are likely underreported due to similar presentation to other diseases and subsequent misdiagnosis. the misdiagnosis or delayed diagnosis of patients with epd is often fueled by a history of or coexistence of actinic keratoses and other keratinocytic carcinomas.2 these diagnoses have led to months of non-productive treatment consequently prescribed to the patients, such as imiquimod and 5-fluorouracil, which may further contribute to the progression of epd without effectively treating the underlying condition.3,4 the pathology of epd occurs below the crust, which is why our patient returned to the office for complete debridement of the crusted plaque (figure 1b) after a diagnosis of epd was made. the histopathology of epd is often variable and non-specific, highlighting the importance of clinicopathological correlation.5 despite the lack of pathognomonic pathology, a biopsy remains essential to help rule out other differential entities, including malignant processes, infective, inflammatory (i.e., folliculitis decalvans), autoimmune (i.e., pemphigus, cicatricial pemphigoid, discoid lupus erythematosus), and psychosomatic.1 additionally, a wound culture is also recommended as concurrent bacterial infection is common with epd and should be treated, as in this case.1,6 superpotent topical corticosteroids have historically been first-line treatment for epd but are often used with variable success as refractory disease is not uncommon.1,5 the presentation of epd in this case illustrates the requirement for thoughtful workup and clinicopathological correlation given the significant overlap that occurs in patient demographics, risk factors, and skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 185 lesion morphology with keratinocytic carcinomas and epd. therefore, epd must remain an important diagnostic consideration in elderly patients with lesions suspicious of cutaneous malignancies, as proper workup can potentially spare the patient weeks of non-productive therapy and optimize recovery. conflict of interest disclosures: none funding: none corresponding author: jesse veenstra, md, phd department of dermatology henry ford health system 3031 w. grand blvd, ste 800 detroit, mi 48202 jjveenst1@gmail.com references: 1. yeh r, polcz m, wong d. erosive pustular dermatosis of the scalp an australian perspective: insights to aid clinical practice. australas j dermatol 2019; 60: e272-e8. 2. piccolo v, russo t, bianco s et al. erosive pustular dermatosis of the scalp: why do we miss it? dermatology (basel, switzerland) 2019; 235: 390-5. 3. corradin mt, forcione m, giulioni e et al. erosive pustular dermatosis of the scalp induced by imiquimod. case rep dermatol med 2012; 2012: 828749. 4. rongioletti f, delmonte s, rossi me et al. erosive pustular dermatosis of the scalp following cryotherapy and topical tretinoin for actinic keratoses. clin exp dermatol 1999; 24: 499-500. 5. starace m, alessandrini a, baraldi c et al. erosive pustular dermatosis of the scalp: challenges and solutions. clin cosmet investig dermatol 2019; 12: 691-8. 6. thuraisingam t, mirmirani p. erosive pustular dermatosis: a manifestation of immunosenescence a report of 8 cases. skin appendage disord 2018; 4: 180-6. tralokinumab (n=1605; pye=473.19) placebo (n=680; pye=193.1) preferred term n (adj. %) e adj. r n (adj. %) e adj. r any aes 38 (2.3) 47 9.9 20 (2.8) 25 13.3 dermatitis atopic 7 (0.4) 7 1.3 10 (1.5) 10 5.5 injection site reaction 5 (0.3) 5 1.0 0 0 0 eosinophilia 3 (0.2) 3 0.5 0 0 0 conjunctivitis 2 (0.1) 2 0.4 0 0 0 table 4. most frequent aes leading to permanent discontinuation of study drug by preferred terma (safety analysis set, ad pool, initial treatment period) introduction results methods objective ecztra 1 and ecztra 2 ecztra 3 ecztra 5 phase 2b triala number of patients in analysis set tralokinumab 300 mg q2w ecztra 1: 602 ecztra 2: 592 placebo ecztra 1: 196 ecztra 2: 200 tralokinumab 300 mg q2w 252 placebo 126 tralokinumab 300 mg q2w 107 placebo 107 tralokinumab 300 mg q2w 52 placebo 51 eligibility criteria • ≥18 years of age • confirmed diagnosis of ad for >1 year • ad body surface area involvement >10% • easi scores ≥12 at screening and ≥16 at baseline • iga score ≥3 • pruritus nrs ≥4 • ≥18 years of age • confirmed diagnosis of ad for >1 year • ad body surface area involvement ≥10% • easi scores ≥12 at screening and ≥16 at baseline • iga score ≥3 • pruritus nrs ≥4 • 18–54 years of age • confirmed diagnosis of ad for >1 year • ad body surface area involvement ≥10% • easi scores ≥12 at screening and ≥16 at baseline • iga score ≥3 • 18–75 years of age • confirmed diagnosis of ad for .1 year • ad body surface area involvement >10% • easi score >12 • iga score >3 treatment • patients were randomized 3:1 to sc tralokinumab 300mg q2w or placebo q2w for 16 weeks • at 16 weeks, tralokinumab respondersb were rerandomized 2:2:1 to maintenance treatment with sc tralokinumab q2w or q4w or placebo q2w for an additional 36 weeks • placebo responders continued with placebo • non-responders received sc tralokinumab q2w + optional tcs for an additional 36 weeks • patients who met the predefined criteria during the maintenance treatment period were transferred to open label and received tralokinumab 300 mg q2w with optional use of tcs • patients were randomized 2:1 to sc tralokinumab 300 mg sc q2w + tcs or placebo q2w + tcs for 16 weeks • at 16 weeks, tralokinumab respondersb were re-randomized 1:1 to continuation treatment with sc tralokinumab q2w or q4w + tcs for an additional 16 weeks • placebo responders continued with placebo • non-responders received sc tralokinumab q2w + tcs for an additional 16 weeks • patients were randomized 1:1 to sc tralokinumab 300 mg q2w or placebo q2w • patients were randomized 1:1:1:1 to sc tralokinumab 45 mg, 150 mg or 300 mg q2wc + tcs or to placebo q2w + tcs table 1. number of patients by trial, eligibility criteria and treatment conclusions ● in this analysis of five clinical trials (three phase 3 and two phase 2), which included 2285 patients, tralokinumab 300 mg q2w was well tolerated when used as monotherapy and as combination therapy with tcs for treatment of moderate-to-severe ad in the ad pool during the initial 16-week period ● the overall frequencies of aes were similar for tralokinumab and placebo; skin infections requiring systemic treatment, eczema herpeticum, opportunistic infections and severe or serious infections were lower with tralokinumab than with placebo ● the safety profile during prolonged tralokinumab treatment was consistent with the initial 16-week treatment period and some events decreased in frequency references 1. nutten s. ann nutr metab 2015; 66(suppl 1): 8–16. 2. weidinger s, novak n. lancet 2016; 387: 1109–1122. 3. eckert l et al. j am acad dermatol 2017; 77: 274–279.e273. 4. silverberg ji et al. ann allergy asthma immunol 2018; 121: 340–347. 5. dalgard fj et al. j invest dermatol 2015; 135: 984–991. 6. bieber t. allergy 2020; 75: 54–62. 7. tsoi lc et al. j invest dermatol 2019; 139: 1480–1489. 8. popovic b et al. j mol biol 2017; 429: 208–219. 9. wollenberg a et al. j allergy clin immunol 2019; 143: 135–141. 10. augustin m et al. j eur acad dermatol venereol 2020; 34: 142–152. disclosures eric simpson reports grants and personal fees from abbvie, leo pharma, lilly, medimmune, pfizer and regeneron; grants from celgene, galderma, kyowa hakko kirin, merck, novartis and tioga; and personal fees from boehringer ingelheim, dermavant, dermira, fortébio, incyte, menlo therapeutics, ortho dermatologics, pierre fabre, sanofi and valeant. joseph f. merola has served as an advisor or consultant for: abbvie inc.; aclaris; almirall hermal gmbh ; celgene corporation; dermavant sciences, inc.; eli lilly and company; glaxosmithkline; incyte corporation; janssen pharmaceuticals; leo pharma; merck & co., inc.; novartis pharmaceuticals corporation; pfizer inc.; regeneron pharmaceuticals, inc.; sanofi; sun pharmaceutical industries, ltd.; and ucb pharma, inc. he has served as an investigator for abbvie inc.; aclaris; almirall hermal gmbh ; celgene corporation; dermavant sciences, inc.; eli lilly and company; glaxosmithkline; incyte corporation; janssen pharmaceuticals; leo pharma; merck & co., inc. jonathan i. silverberg has received grants, personal fees, or nonfinancial support from abbvie, anaptysbio, arena, asana, boehringer ingelheim, celgene, dermavant, dermira, lilly, galderma, glaxosmithkline, kiniksa, leo pharma, medimmune, menlo, novartis, pfizer, regeneron, and sanofi. rebecca zachariae and christina kurre olsen are employees of leo pharma. andreas wollenberg has received grants, personal fees, or nonfinancial support from abbvie, almirall, beiersdorf, bioderma, chugai, galapagos, galderma, hans karrer, leo pharma, lilly, l’oreal, maruho, medimmune, novartis, pfizer, pierre fabre, regeneron, santen, and sanofi-aventis.the ecztra clinical trials were sponsored by leo pharma. the phase 2b trial was sponsored by medimmne/astrazeneca safety of specifically targeting interleukin 13 with tralokinumab in adult patients with moderate-to-severe atopic dermatitis: pooled analysis of five randomized, double-blind, placebo-controlled phase 3 and phase 2 trials eric simpson,1 joseph f merola,2 jonathan i silverberg,3 rebecca zachariae,4 christina kurre olsen,4 andreas wollenberg5 1department of dermatology, oregon health & science university, portland, or, usa; 2brigham and women’s hospital and harvard medical school, boston, ma, usa; 3department of dermatology, the george washington university school of medicine and health sciences, washington, dc, usa; 4leo pharma a/s, ballerup, denmark; 5klinikum der universität münchen, klinik und poliklinik für dermatologie und allergologie, munich, germany ● atopic dermatitis (ad) is a chronic, debilitating, inflammatory skin disease1,2 characterised by eczematous lesions and multiple symptoms, including pruritus, sleep disturbance and depression.3-5 the type 2 cytokine interleukin 13 (il-13) is a key driver of the underlying inflammation of ad and is overexpressed in lesional and non-lesional ad skin6,7 ● tralokinumab is a fully human immunoglobulin g4 monoclonal antibody that specifically binds to the il-13 cytokine with high affinity, preventing interaction with the il-13 receptor and subsequent downstream il-13 signalling, thus preventing its pro-inflammatory activity6-8 ● tralokinumab 300 mg every 2 weeks (q2w), as monotherapy and in combination with topical corticosteroids (tcs), was efficacious in the treatment of patients with moderate-to-severe ad in three pivotal phase 3 ecztra trials (ecztra 1 [nct03131648], ecztra 2 [nct03160885] and ecztra 3 [nct03363854]), a phase 2 trial (ecztra 5 [nct03562377]) and a phase 2b trial (nct02347176)9 ● it is important to understand the safety profile of therapeutics used for the long-term treatment of patients with ad — a good safety profile is an important attribute for patients when selecting a treatment for ad10 study designs ● five placebo-controlled trials formed the ad pool: phase 3 (ecztra 1, ecztra 2 and ecztra 3), phase 2 (ecztra 5) and phase 2b ● ecztra 1 and ecztra 2 were identically designed, multinational, double-blind, randomized, placebo-controlled, 52-week clinical trials of tralokinumab monotherapy ● ecztra 3 was a multinational, double-blind, randomized, placebo-controlled, 32-week clinical trial of tralokinumab in combination with tcs ● ecztra 5 was a multinational, double-blind, randomized, placebo-controlled, 16-week clinical trial to evaluate the effect of tralokinumab monotherapy on vaccine antibody responses ● the phase 2b trial was a multinational, double-blind, randomized, placebo-controlled, 12-week dosing study of tralokinumab, in combination with tcs patients and treatment ● patients in all five trials were adults ≥18 years of age with a confirmed diagnosis of ad for > 1 year and an investigator’s global assessment (iga) score ≥3 (table 1) ● patients were randomized to tralokinumab 300 mg q2w or placebo with or without tcs safety analysis ● the safety analysis was based on the safety analysis set, which comprised all randomized patients who were exposed to investigational medicinal product ● the safety analysis was performed for the initial 16-week (ecztra trials) and 12-week (phase 2) treatment periods (ad pool), and for the long-term, 36-week maintenance period in the ecztra 1 and ecztra 2 trials (monotherapy pool) for tralokinumab 300 mg q2w ● an analysis of adverse events (aes) of special interest (aesis), including skin infections requiring systemic treatment, eczema herpeticum, eye disorders (conjunctivitis, keratoconjunctivitis and keratitis) and malignancies diagnosed after randomisation, was pre-specified in the study protocol ● all aes described were treatment emergent, defined as aes reported after the first dosing of the study drug ● aes are summarised by the number and proportion of patients with aes and the number and rate of events by treatment group patient demographics and clinical characteristics ● for the initial treatment period, the ad pool included 2285 patients: 1605 treated with tralokinumab 300 mg q2w (exposure for the entire treatment period, 1403.9 pye) and 680 with placebo q2w (exposure for the entire treatment period, 272.6 pye) — patient demographics and clinical characteristics were similar across treatment arms (table 2) tralokinumab (n=1605) placebo (n=680) sex, n (%) male 921 (57.4) 375 (55.1) female 684 (42.6) 305 (44.9) mean age, years (sd) 37.9 (14.3) 37.0 (14.3) age group, n (%) 18–64 years 1528 (95.2) 648 (95.3) 65 years 77 (4.8) 32 (4.7) median age at onset of ad, years 3.0 3.0 mean duration of ad, years (sd) 27.7 (15.4) 27.7 (15.2) mean body surface area, % (sd) 51.0 (24.4) 50.2 (24.7) iga, n (%) iga-3 (moderate) 840 (52.3) 362 (53.2) iga-4 (severe) 762 (47.5) 318 (46.8) iga-5 (very severe) 3 (0.1) 0 race, n (%) white 1089 (67.9) 430 (63.2) black or african american 139 (8.7) 80 (11.8) asian 324 (20.2) 143 (21.0) other 47 (2.9) 19 (2.8) missing 6 (0.4) 8 (1.2) ethnicity, n (%) hispanic or latino 169 (7.4) 56 (8.2) not hispanic or latino 2111 (92.4) 621 (91.3) missing 5 (0.2) 3 (0.4) table 2. baseline patient demographics and clinical characteristics (safety analysis set, ad pool) sd, standard deviation. ● medical dictionary for regulatory activities (meddra) version 2.0 was used ● event rates are presented as the number of events per 100 patient-years of exposure (pye) statistical analysis ● cochran-mantel-haenszel weights were applied to calculate adjusted ae incidences for the initial treatment period to account for varying randomisation rates between tralokinumab and placebo in the trials ● risk ratios were estimated from a poisson regression with treatment as fixed effect, and log values of pye were used as offset variable a50 patients received 45 mg tralokinumab and 51 patients received 150 mg tralokinumab. these two low doses were not included in the ad pool; bdefined as being iga-0/1 and/or easi-75 responders at week 16; conly the tralokinumab 300 mg q2w group was included in the pooled analysis. easi, eczema area and severity index; nrs, numeric rating scale; sc, subcutaneous. ad pool monotherapy pool tralokinumab (n=1605; pye=473.19) placebo (n=680; pye=193.1) tralokinumab (n=1194; pye=354.46) placebo (n=396; pye=114.47) n (adj. %) e adj. r n (adj. %) e adj. r n (%) e adj. r n (%) e adj. r events 1080 (65.7) 3148 639.5 449 (67.2) 1276 678.3 824 (69.0) 2479 699.4 283 (71.5) 899 785.3 serious 37 (2.1) 38 7.4 18 (2.8) 22 11.9 33 (2.8) 34 9.6 13 (3.3) 17 14.9 severity mild moderate severe 881 (53.2) 518 (31.5) 77 (4.6) 2127 917 104 429.8 189.5 20.2 326 (49.0) 258 (39.0) 40 (6.3) 738 478 60 391.0 254.3 33.0 673 (56.4) 409 (34.3) 65 (5.4) 1654 733 92 466.6 206.8 26.0 204 (51.5) 182 (46.0) 32 (8.1) 500 350 49 436.8 305.7 42.8 drug withdrawn (action taken) 38 (2.3) 47 9.9 20 (2.8) 25 13.3 29 (2.4) 34 9.6 11 (2.8) 16 14.0 outcome fatal not recovered/not resolved recovering/resolving recovered/resolved recovered/resolved with sequelae unknown 1 (0.1) 232 (14.3) 79 (5.0) 997 (60.2) 18 (1.0) 27 (1.7) 1 312 87 2699 18 31 0.4 65.4 18.9 544.5 3.5 7.0 0 90 (13.5) 36 (5.4) 416 (62.4) 2 (0.3) 6 (0.9) 0 126 45 1096 3 6 0 65.2 22.7 585.4 1.7 3.3 0 167 (14.0) 56 (4.7) 769 (64.4) 15 (1.3) 21 (1.8) 0 229 60 2152 15 23 0 64.6 16.9 607.1 4.2 6.5 0 60 (15.2) 22 (5.6) 264 (66.7) 2 (0.5) 4 (1.0) 0 78 25 789 3 4 0 68.1 21.8 689.2 2.6 3.5 table 3. overall safety summary (safety analysis set, initial treatment period) adj., adjusted; e, event; r, rate, pye, patient-years of exposure ● the monotherapy pool included 1590 patients: 1194 treated with tralokinumab 300 mg and 396 treated with placebo q2w ● as the monotherapy pool constituted the majority of the ad pool, the monotherapy pool resembled the ad pool in baseline demographics and clinical characteristics, with no major differences between patients in the tralokinumab q2w and placebo treatment groups safety: ad pool (initial treatment period) ● the overall frequency of aes was similar for tralokinumab (65.7%) and placebo (67.2%) (table 3) — the majority of aes (90%) were mild or moderate in severity ● the majority of aes were recovered/resolved for tralokinumab (60.2%) and placebo (62.4%) ● the most frequently occurring aes (defined by meddra preferred term [meddra pt]) in 5% of patients for tralokinumab and placebo were atopic dermatitis (15.4% vs 26.2%), viral upper respiratory tract infection (15.7% vs 12.2%), upper respiratory tract infection (5.6% vs 4.8%) and conjunctivitis (5.4% vs 1.9%) (figure 1) — nearly two-thirds of the events related to upper respiratory tract infections (including viral upper respiratory tract infection) were reported as common cold with tralokinumab (64%) and placebo (65%). the majority of the events were classified as mild and none were serious aes (saes), severe aes nor aes leading to permanent discontinuation of tralokinumab rradj. % n=680 e (placebo) tralokinumab placebo 0 252015105 30 0.1 1 10 favors tralokinumab favors placebo dermatitis atopic viral upper respiratory tract infection upper respiratory tract infection headache pruritus injection site pain nausea asthma diarrhoea influenza dermatitis infected conjunctivitis allergic skin infection injection site reaction conjunctivitis adj. % tralokinumab 15.4 15.7 5.6 4.6 2.6 2.3 1.0 1.5 1.8 1.3 0.5 2.0 1.1 3.5 5.4 adj. r 68.0 65.1 20.8 21.6 10.6 13.4 4.2 6.5 6.8 4.5 1.6 7.1 4.0 22.9 21.0 placebo adj. % 26.2 12.2 4.8 3.9 3.0 1.7 1.9 1.8 1.6 1.7 1.8 1.1 2.5 0.3 1.9 adj. r 139.7 53.5 18.5 19.6 13.1 11.8 7.3 6.4 6.1 6.1 8.8 4.3 9.0 4.0 6.9 n=1605 e (tralokinumab) 356 309 100 102 57 69 22 32 33 24 9 36 21 110 104 rr (95% ci) 0.6 (0.5, 0.7) 1.3 (1.0, 1.6) 1.1 (0.8, 1.7) 1.1 (0.8, 1.6) 1.0 (0.6, 1.6) 1.3 (0.8, 2.2) 0.6 (0.3, 1.3) 1.1 (0.6, 2.1) 1.1 (0.6, 2.2) 0.9 (0.4, 1.8) 0.2 (0.1, 0.5) 1.8 (0.9, 4.0) 0.5 (0.3, 1.0) 6.4 (3.0, 13.8) 3.3 (1.8, 5.8) p value �.0001 0.0362 0.5189 0.5394 0.8977 0.2392 0.1938 0.8027 0.7323 0.7498 0.0002 0.1199 0.0599 �.0001 �.0001 256 99 36 37 24 21 14 12 12 11 17 8 16 7 13 figure 1. the 15 most frequent aes by preferred terma (safety analysis set, ad pool, initial treatment period) ameddra pt. ci, confidence interval; rr, risk ratio. dermatitis atopic viral upper respiratory tract infection upper respiratory tract infection headache oral herpes injection site pain influenza asthma hypertension pruritus conjunctivitis allergic dry eye back pain injection site reaction conjunctivitis bronchitis % r tq2w/tq2w 15.1 14.5 9.4 2.5 5.0 3.8 3.8 3.1 0.6 1.3 3.8 3.8 1.3 5.0 5.7 46.0 31.9 22.4 4.7 16.5 7.1 8.3 5.9 1.2 2.4 16.5 9.4 4.7 13.0 29.5 tq2w/tq4w % 17.0 14.5 6.7 6.1 2.4 2.4 2.4 2.4 0.0 1.8 3.0 3.6 1.8 3.0 6.7 r 46.8 36.5 17.1 12.6 4.6 6.8 4.6 4.6 0.0 3.4 5.7 6.8 3.4 8.0 28.5 % r tq2w/placebo 27.2 13.6 4.9 2.5 3.7 3.7 2.5 3.7 3.7 3.7 0.0 0.0 1.2 2.5 1.2 88.9 31.4 10.5 5.2 15.7 10.5 5.2 7.8 10.5 7.8 0.0 0.0 2.6 5.2 2.6 placebo/placebo % 13.3 10.0 5.0 3.3 0.0 1.7 0.0 0.0 0.0 0.0 0.0 1.7 5.0 1.7 0.0 r 41.1 37.7 10.3 6.9 0.0 3.4 0.0 0.0 0.0 0.0 2.5 4.7 3.6 8.0 3.7 10.5 3.3 6.9 0.0 3.4 13.7 3.4 0.0 patients, % tq2w/tq2w tq2w/placebo tq2w/tq4w placebo/placebo 0 252015105 30 35 figure 2. the 15 most frequent aes by preferred terma (safety analysis set, monotherapy pool, maintenance treatment period) ameddra pt. %, percentage of patients with one or more events; placebo/placebo, week 16 placebo responder who continued on placebo; t, tralokinumab; tq2w/tq2w, week 16 tralokinumab responder who continued on tralokinumab every 2 weeks; tq2w/tq4w, week 16 tralokinumab responder re-randomized to tralokinumab every 4 weeks; tq2w/placebo, week 16 tralokinumab responder re-randomized to placebo. ● saes were lower for tralokinumab (2.1%) than for placebo (2.8%) ● the frequencies of severe (0.6% vs 1.4%) or serious (0.4% vs 1.1%) infections were lower for tralokinumab than for placebo ● the proportion of aes leading to permanent discontinuation up to 16 weeks of treatment was low and similar for tralokinumab (2.3%) and placebo (2.8%) (table 4) ad pool (initial treatment period): aesis ● the incidence of conjunctivitis (aesi term) was higher with tralokinumab (7.5%) versus placebo (3.2%) (table 5) but the majority of events were mild or moderate (98%) and resolved during treatment; two cases of conjunctivitis led to permanent discontinuation ● a lower incidence of skin infection (aesi) requiring systemic treatment was observed for tralokinumab (2.6%) versus placebo (5.5%) ● the frequency of eczema herpeticum (aesi) was lower for tralokinumab (0.3%) than for placebo (1.5%) safety: monotherapy pool (initial and maintenance treatment period) ● the overall frequency of aes during the initial treatment period was similar for tralokinumab (69.0%) and placebo (71.5%) and similar to the ad pool — the majority of aes were mild or moderate in severity ● the safety profile during prolonged tralokinumab treatment from 16–52 weeks in the monotherapy pool was consistent with the initial 16-week treatment period, based on overall frequencies of aes, saes, severe aes and aes leading to permanent discontinuation (figure 2) ● the overall rate of aes for tralokinumab q2w during the maintenance treatment period was lower than in the initial treatment period (499.3 vs 699.4 events per 100 pye) and higher than patients re-randomized to tralokinumab every 4 weeks (q4w) or placebo (414.2 and 442.1 events per 100 pye, respectively) ● the most frequently occurring aes (in 5% of patients [meddra pt]) for all treatment groups during the maintenance period were generally in line with the most frequently occurring aes during the initial treatment period in the ad pool and were atopic dermatitis, viral upper respiratory tract infection, upper respiratory tract infection and injection site reaction ● lower rates of saes, severe aes and aes leading to permanent discontinuation were also seen for tralokinumab in the maintenance versus initial treatment period ● to provide an overview of the pooled safety data from three phase 3 ecztra trials and two phase 2 trials to evaluate the safety of tralokinumab 300 mg q2w in adult patients with moderate-to severe ad only events that occurred in 1 patient per preferred term are presented. ameddra pt. pye, patient-years of exposure tralokinumab (n=1605; pye=473.19) placebo (n=680; pye=193.1) soc preferred term n (adj. %) e adj. r n (adj. %) e adj. r any eczema herpeticum aesis infections and infestations eczema herpeticum 6 (0.3) 6 (0.3) 6 (0.3) 6 6 6 1.2 1.2 1.2 10 (1.5) 10 (1.5) 10 (1.5) 10 10 10 5.2 5.2 5.2 any malignancies aesis neoplasms benign, malignant and unspecified (including cysts and polyps) angiosarcoma 1 (0.1) 1 (0.1) 1 (0.1) 1 1 1 0.2 0.2 0.2 0 0 0 0 0 0 0 0 0 any skin infection aesis infections and infestations skin infection impetigo dermatitis infected cellulitis staphylococcal skin infection paronychia eczema infected abscess infected dermal cyst skin bacterial infection folliculitis furuncle herpes simplex pyoderma leishmaniasis pilonidal cyst bullous impetigo carbuncle eyelid infection general disorders and administration site conditions injection site reaction 42 (2.6) 41 (2.5) 13 (0.8) 6 (0.4) 6 (0.3) 4 (0.3) 2 (0.2) 2 (0.1) 1 (0.1) 2 (0.1) 1 (0.1) 1 (0.1) 1 (0.1) 1 (0.1) 1 (0.1) 1 (0.1) 1 (0.1) 0 0 0 0 1 (0.1) 1 (0.1) 46 45 13 6 6 4 3 2 1 3 1 1 1 1 1 1 1 0 0 0 0 1 1 9.7 9.5 2.6 1.5 1.1 0.8 0.9 0.4 0.5 0.5 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0 0 0 0 0.2 0.2 35 (5.5) 35 (5.5) 13 (2.1) 4 (0.6) 8 (1.2) 2 (0.3) 4 (0.6) 1 (0.1) 0 0 0 2 (0.3) 0 0 0 0 0 1 (0.2) 1 (0.2) 1 (0.2) 1 (0.2) 0 0 42 42 13 4 10 2 5 1 0 0 0 2 0 0 0 0 0 2 1 1 1 0 0 22.8 22.8 7.3 2.2 5.1 1.0 2.6 0.5 0 0 0 1.1 0 0 0 0 0 1.1 0.6 0.6 0.6 0 0 any eye disorder aesis 132 (7.9) 155 31.1 22 (3.4) 24 12.9 conjunctivitis (aesi category) infections and infestations conjunctivitis conjunctivitis bacterial conjunctivitis viral eye disorders conjunctivitis allergic keratoconjunctivitis (aesi category) eye disorders keratitis atopic keratoconjunctivitis keratitis (aesi category) eye disorders keratitis ulcerative keratitis infections and infestations keratitis viral 126 (7.5) 95 (5.7) 90 (5.4) 4 (0.2) 1 (0.1) 34 (2.0) 34 (2.0) 5 (0.3) 5 (0.3) 4 (0.3) 1 (0.1) 4 (0.2) 4 (0.2) 4 (0.2) 1 (0.1) 0 0 145 109 104 4 1 36 36 5 5 4 1 5 5 4 1 0 0 29.0 21.9 21.0 0.7 0.2 7.1 7.1 1.2 1.2 1.0 0.2 0.9 0.9 0.7 0.2 0 0 21 (3.2) 15 (2.2) 13 (1.9) 1 (0.2) 1 (0.1) 7 (1.1) 7 (1.1) 0 0 0 0 1 (0.2) 0 0 0 1 (0.2) 1 (0.2) 23 15 13 1 1 8 8 0 0 0 0 1 0 0 0 1 1 12.3 8.0 6.9 0.6 0.5 4.3 4.3 0 0 0 0 0.6 0 0 0 0.6 0.6 table 5. aesis by soc and preferred term (safety analysis set, ad pool, initial treatment period) soc, system organ class, pye, patient-years of exposure winter clinical dermatology conference, january 16-24, 2021 skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 150 rising derm stars® long term outcomes for basal cell carcinoma treated with vismodegib extended alternate day dosing ethan routt, md1; desiree ratner md 1department of dermatology, icahn school of medicine at mount sinai, new york, ny background/objectives: management of locally advanced basal cell carcinoma (bcc) has change dramatically since the introduction of vismodegib, a hedgehog pathway inhibitor. while response rates to vismodegib exceeds 30%, nearly 100% of patients on standard dosing experience side effects with many patients discontinuing therapy as a result. alternative dosing regimens have been proposed to increase the therapeutic longevity of vismodegib and we report a novel extended alternate day (ead) dosing for this medication. methods: irb approved retrospective chart review including all locally advanced bcc patients treated by dr. ratner with vismodegib between 1/2015 and 5/2018. all clinical data, including patient and tumor characteristics, patient outcomes, vismodegib dosing schedule and tumor response was extracted from the electronic medical record, compiled and analyzed in microsoft excel. all dosing listed indicates vismodegib 150 mg taken either daily (fda approved) or on a variable alternate day schedule. results: nine total patients were identified, one treated with daily dosing and 8 treated with ead dosing. mean patient age was 84 years with a mean duration of vismodegib therapy of 255 days. six patients went on every other day dosing for a mean of 125 days, every third day dosing for 94 days and up to weekly dosing depending on patient and tumor response. three patients underwent mohs micrographic surgery (mms) while on ead dosing and 4 remained on therapy at the end of the study period. none of the patients on ead dosing discontinued due to side effects and all maintained tumor response (mean 50% reduction in length and width) to medication during the follow up period. discussion: extended alternate day therapy provided effective tumor control over a mean of 8.5 months for seven of the nine patients. all patients on ead dosing experienced a decrease in tumor size, with none exhibiting tumor progression on ead dosing. while a smaller sample size, this is a significant improvement over previously reported outcomes for vismodegib therapy. one patient who discontinued his every five-day vismodegib dosing due to hospitalization did have tumor regrowth, but after resuming therapy with ead dosing, experienced a continued reduction in tumor size. four of nine patients under went mms after starting ead dosing indicating that this schedule may be an effective in those who are unable to tolerate standard vismodegib dosing as a neoadjuvant to mms. skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 151 conclusion: ead dosing provided a titratable, well tolerated regimen for vismodegib therapy that maintained efficacy over eight months or more. clinicians should consider ead dosing for patients who respond to vismodegib but are unable to tolerate its side effects. further study will help determine whether ead dosing might extend vismodegib’s utility, providing an option of lower dose, long-term suppressive therapy for bcc patients unable to tolerate surgery or radiation. impoyz phase iii clinical poster_presented at maui derm 2019 revise 2021 vr4 copy * clobetasol propionate 0.025% cream (n=176) vehicle cream (n=89) *p<.001 40% 30% 20% 10% 0% pa ti en ts , % day 15 30.1% day 15 9.0% day 8 14.2% * day 8 1.1% clobetasol propionate 0.025% cream (n=176) vehicle cream (n=89) 0% -10% -20% -40% -30% -25.1% -7.4% *p<.001 c h an g e in b sa fr om b as el in e, % * a phase 3, randomized, double-blind, vehicle-controlled, multicenter, parallel group trial investigating the efficacy and safety of clobetasol propionate cream, 0.025% in the treatment of moderate to severe plaque psoriasis for 14 days all other trademarks are property of their respective owners. all rights reserved. • the results of this phase 3 trial indicate that clobetasol propionate, 0.025% cream demonstrates superior efficacy in the treatment of moderate to severe plaque psoriasis compared tp vehicle cream. – e�cacy was demonstrated early, at �rst post-treatment visit day 8 (14.2% vs 1.6%). – e�cacy continued during second week of treatment with more subjects in the clobetasol group achieving treatment success at �nal visit day 15 (30% vs 9%). – e�cacy is notable in that all subjects were diagnosed with moderate to severe plaque psoriasis with baseline iga’s of 3 or 4. • the incidence of local cutaneous side e�ects was low and very similar between subjects treated with clobetasol propionate, 0.025% compared to those who received the vehicle. conclusions • to study the efficacy and safety of a lower-concentration clobetasol propionate cream, 0.025% formulated with diethylene glycol monoethyl ether compared to vehicle for the topical treatment of adult moderate to objective trial design and patients • this study was a randomized, multicenter, double-blind, vehicle-controlled trial performed across 27 sites in the united states. • eligible patients included males or females at least 18 years old with moderate to severe plaque psoriasis (stable for a minimum of 3 months) involving ≥3% body surface area (bsa) with an investigators global assessment (iga) score of 3 (moderate) or 4 (severe). • patients were randomized (2:1) to treatment with clobetasol propionate, 0.025 cream or vehicle cream, twice daily for 14 consecutive days. efficacy and safety endpoints • the primary efficacy endpoint was the proportion of subjects with treatment success at day 15 — defined as an iga score of 0 (clear) or 1 (almost clear) and at least a 2-grade reduction from baseline. • secondary efficacy endpoints included the proportion of subjects with treatment success at the day 8 visit and the percent change in a�ected bsa from baseline to the day 15 visit. • the primary safety assessment included evaluation by the site investigator for local cutaneous adverse events at all visits beyond baseline. statistical analysis • for analysis of the primary efficacy endpoint, a cochran-mantel-haenszel (cmh) test for general association, stratified by analysis center, was performed to assess the di�erence in proportion of subjects with treatment success at day 15 between the treatment and vehicle groups. – signi�cance testing for percent change in bsa from baseline was performed using a 2-way analysis of variance (anova). – proportion of subjects with treatment success at day 8 was analyzed using a cmh test. • safety outcomes were assessed for the entire population of subjects who received at least 1 confirmed dose of study product and provided any postbaseline safety information. no imputations were made for missing safety data. • all statistical analyses were performed using sas version 9.1.3 statistical software (cary, nc). methods results demographics • two hundred ninety subjects were screened for potential inclusion. of these, 265 were randomized: 176 to the clobetasol group and 89 to the vehicle group. – overall, 260 (98.1%) subjects completed the study, 175 (99.4%) in the clobetasol propionate group and 85 (95.5%) in the vehicle group. • demographic and disease characteristics were relatively equally distributed between the 2 groups (table 1). – the only statistically signi�cant di�erence between the groups was the proportion of subjects age 65 or older ( p =.047). • topical corticosteroids continue to play a vital role in the management of numerous inflammatory skin conditions. • however, the management of potential side e�ects remains a challenge, especially when introducing molecules with a higher potency. • an alternative concentration of clobetasol propionate cream 0.025% (impoyz®) formulated with diethylene glycol monoethyl ether (transcutol p®), a drug solubility and permeation enhancer, demonstrated a lower degree of systemic exposure compared to the traditional 0.05% concentration of clobetasol propionate cream.1 • this study reports the e�cacy and safety of clobetasol propionate cream 0.025% formulated with diethylene glycol monoethyl ether in adult patients with moderate to severe plaque psoriasis. figure 1. percentage of study participants achieving treatment success table 1. baseline demographic characteristics ap value for significance testing for di�erences between clobetasol propionate, 0.025% and vehicle groups bcochran-mantel-haenszel test for general association, adjusted for site ctwo-way analysis of variance (anova) dat baseline bsa = body surface area; iga = investigator’s global assessment randomization group clobetasol propionate, 0.025% cream (n=176) vehicle cream (n=89) total (n=265) p-valuea gender (n, %) 0.343b male 111 (63.1%) 51 (57.3%) 162 (61.1%) female 65 (36.9%) 38 (42.7%) 103 (38.9%) mean age ± sd 49.5 ± 13.6 50.6 ± 15.9 49.8 ± 14.4 0.377c age (n, %) 0.047b < 65 years 152 (86.4%) 70 (78.7%) 222 (83.8%) 65 years or older 24 (13.6%) 19 (21.3%) 43 (16.2%) baseline iga (n, %)d 0.892b 0 (clear) 0 (0) 0 (0) 0 (0) 1 (almost clear) 0 (0) 0 (0) 0 (0) 2 (mild) 0 (0) 0 (0) 0 (0) 3 (moderate) 142 (80.7%) 72 (80.9%) 214 (80.8%) 4 (severe) 34 (19.3%) 17 (19.1%) 51 (19.2%) mean bsa (%) % +/sdd 8.7 ± 10.2 9.2 ± 11.3 8.8 ± 10.6 0.436c improvement in treatment success • a significantly greater proportion of patients in the clobetasol propionate group experienced treatment success at day 15 (30.1%) compared to patients who received vehicle (9.0%; p<.001; figure 1). – treatment success was de�ned as an iga score of 0 (clear) or 1 (almost clear). • the proportion of patients with treatment success at day 8 was significantly greater in the clobetasol propionate, 0.025% group compared to the vehicle group (14.2% vs 1.1%, p<.001; figure 1). reduction in psoriasis-a�ected bsa • the reduction in mean bsa involvement from baseline to day 15 was significantly greater in the clobetasol propionate, 0.025% group compared to the vehicle group (-25.1% vs -7.4%, p<.001; figure 2). figure 2. mean percent change in bsa involvement to day 15 this submission was supported by primus pharmaceuticals. srd, zdd, srf, jmj have not received honoraria for consulting services from primus pharmaceuticals. medical writing assistance was provided by jennifer l dreyer, phd, and lori johnson, phd of 7west communications, fort worth, tx. reference: 1. draelos, z. d., fowler, j. f., & cornelison, r. (2018). a randomized, parallel group, open label, multicenter study to assess the potential for adrenal suppression and systemic drug absorption following multiple dosing with clobetasol propionate cream (impoyz™), 0.025% versus clobetasol propionate (temovate®). skin the journal of cutaneous medicine, 2(6). https://doi.org/10.25251/skin.2.6.16 local cutaneous signs & symptoms treatment group day 1 (baseline) n (%) day 15 n (%) atrophy clobetasol propionate, 0.025% 1/176 (0.6%) 1/171 (0.6%) vehicle 2/89 (2.2%) 2/83 (2.4%) telangiectasia clobetasol propionate, 0.025% 0/176 (0.0%) 0/171 (0.0%) vehicle 1/89 (1.1%) 0/83 (0.0%) burning/stinging clobetasol propionate, 0.025% 34/176 (19.3%) 10/171 (5.8%) vehicle 18/89 (20.2%) 9/83 (10.8%) pruritus clobetasol propionate, 0.025% 91/176 (51.7%) 22/171 (12.9%) vehicle 46/89 (51.7%) 19/83 (22.9%) striae clobetasol propionate, 0.025% 3/176 (1.7%) 1/171 (0.6%) vehicle 0/89 (0.0%) 0/83 (0.0%) hypopigmentation clobetasol propionate, 0.025% 5/176 (2.8%) 6/171 (3.5%) vehicle 4/89 (4.5%) 1/83 (1.2%) fissuring clobetasol propionate, 0.025% 0/176 (0.0%) 0/171 (0.0%) vehicle 3/89 (3.4%) 7/83 (8.4%) folliculitis clobetasol propionate, 0.025% 0/176 (0.0%) 0/171 (0.0%) vehicle 0/89 (0.0%) 0/83 (0.0%) safety endpoints • in general, the proportion of subjects experiencing local cutaneous adverse events decreased progressively throughout the study period (table 2). • at day 15, the proportion of subjects experiencing atrophy, burning/stinging, pruritus, and fissuring was lower in the clobetasol propionate, 0.025% group compared to the vehicle group. • the proportion of subjects experiencing striae (0.0% vs 0.6%) and hypopigmentation (1.2% vs 3.5%) were both lower in the vehicle group. • no subjects in either group exhibited telangiectasia or folliculitis at day 15. table 2. proportion of subjects experiencing local cutaneous signs & symptoms seemal r. desai, m.d. innovative dermatology, pa plano, tx the university of texas southwestern medical center dallas, tx zoe diana draelos, m.d. dermatology consulting services, pllc high point, nc steven r. feldman, m.d., ph.d. wake forest school of medicine winston-salem, nc j. mark jackson, m. d. the university of louisville louisville, ky synopsis ©2021 primus pharmaceuticals, inc. scottsdale, az 85253 severe plaque psoriasis. skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 180 skimages auricular distortion following cryotherapy jason t. bard, bs1, heather a. kornmehl, md1, joseph m. wentzell, md, faad, facms1 1 eastern virginia medical school, norfolk, va cryotherapy is widely utilized in dermatologic practice for the treatment of more than 50 conditions.1 potential complications of cryotherapy include scarring, dyspigmentation, infection, and hair loss. in terms of efficacy, one of the largest prospective studies on cryotherapy for the treatment of actinic keratosis found an overall complete response rate of 67.2%. about half of patients reported burning or stinging pain during treatment; no serious reactions were reported.2 the ears, particularly in shorter haired individuals, are a common site of actinic damage and are therefore commonly treated with cryotherapy techniques.3,4 skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 181 we report a case of external ear architecture distortion following cryotherapy. a 52-yearold otherwise healthy female with no underlying disease presented for treatment of a recurrent actinic keratosis of the helical rim six months after a session of cryotherapy (two freeze-thaw cycles) by an outside practitioner. by report, her ear was anatomically normal prior to treatment. physical examination demonstrated the recurrent actinic keratosis and fusion of her helix and antihelix with obliteration of the scaphoid fossa (figure 1). unfortunately, this is not an isolated case. we have seen this complication before through referrals from outside sources, however, to our knowledge, there are no published cases in the literature of helix-antihelix fusion as a complication of cryotherapy. scarring is a known potential complication of cryotherapy.1 however, it is not clear that collagen scarring is the mechanism of this helix-antihelix fusion. rather, we postulate the mechanism is adhesions secondary to re-epithelialization of the suprabasilar stratum malpighii layers. this process bridges the contours of the epidermis without necessarily invoking a process of scarring. this adhesion between helix and antihelix can occur with or without epidermal damage to the intervening scaphoid fossa. this is analogous to other better-known epidermal injury adhesions such as labial fusion, nasal synechiae, finger fusion, or adhesion of skin folds due to epidermal damage in pemphigus. in fact, the cumulative effect of strong keratinocyte cellcell adhesion during the healing process is the likely mechanism for the fusion process, without stimulating collagen damage and repair.5 this epidermal adhesion process can create contour distortion in the absence of dermal damage. correction of fusion between the helix and antihelix of the ear requires surgical separation of the helix and antihelix. as such, practitioners should account for the risk of epidermal fusion of the external ear’s architecture prior to performing cryotherapy on both the antihelix and helix. a potential solution is to refrain from treating both areas simultaneously, allowing each anatomic site to heal before the other is treated, while avoiding damage to the intervening scaphoid fossa. although, we recognize multiple appointments may result in increased healthcare costs. to prevent unintended overspray between the helix and the antihelix, a structural shield can be applied to protect adjacent skin. lastly, it may be helpful to limit the extent of the freezing process. this reasoning can be applied to other destructive treatments resulting in re-epithelialization of the epidermis, such as 5-fluorouracil application. conflict of interest disclosures: none funding: none corresponding author: jason bard 721 fairfax avenue, suite 200 norfolk, va 23507 email: bardjt@evms.edu references: 1. afsar fs, erkan cd, karaca s. clinical practice trends in cryosurgery: a retrospective study of cutaneous lesions. postepy dermatol alergol. 2015;32(2):88-93. doi: 10.5114/pdia.2015.48048. 2. thai ke, fergin p, freeman m, et al. a prospective study of the use of cryosurgery for the treatment of actinic keratoses. int j dermatol. 2004; 43(9):687-92 3. ibrahim sf, brown md. actinic keratoses: a comprehensive update. j clin aesthet dermatol. 2009;2(7):43-48. 4. ferrándiz c, plazas mj, sabaté m, palomino r. prevalence of actinic keratosis among mailto:bardjt@evms.edu skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 182 dermatology outpatients in spain. actas dermosifiliogr. 2016;107(8):674-80. doi: 10.1016/j.ad.2016.05.016. 5. evans nd, oreffo ro, healy e, thurner pj, man yh. epithelial mechanobiology, skin wound healing, and the stem cell niche. j mech behav biomed mater. 2013;28:397-409. doi: 10.1016/j.jmbbm.2013.04.023. tapinarof cream 1% once daily for the treatment of moderate to severe atopic dermatitis in children and adults: the pivotal phase 3 adoring clinical program lawrence f. eichenfield,1,2 jonathan i. silverberg,3 robert bissonnette,4 anna m. tallman,5 philip m. brown,5 david s. rubenstein,5 stephen c. piscitelli,5 john e. jett5 1school of medicine, university of california, san diego, ca, usa; 2rady children’s hospital, san diego, ca, usa; 3school of medicine and health sciences, the george washington university, dc, usa; 4innovaderm research inc., montreal, qc, canada; 5dermavant sciences, inc., morrisville, nc, usa synopsis ■ atopic dermatitis (ad) is a chronic, relapsing, and remitting inflammatory skin disease characterized by intense pruritus and eczematous lesions that can substantially impact sleep and quality of life1–4 ■ in the us, approximately 16.5 million adults and 9.6 million children under the age of 18 years have ad5 ■ there is a need for efficacious non-steroidal topical therapies for ad without restrictions on duration, extent or site of use ■ tapinarof is a novel, first-in-class, small-molecule topical therapeutic aryl hydrocarbon receptor modulating agent (tama) in development for the treatment of ad and psoriasis. tapinarof has demonstrated efficacy and a remittive effect in phase 3 clinical trials for the treatment of plaque psoriasis: psoaring 1 (nct03956355), psoaring 2 (nct03983980), and psoaring 3 (nct04053387) ■ tapinarof specifically binds to and activates the aryl hydrocarbon receptor (ahr), a ligand-dependent transcription factor. this leads to the downregulation of inflammatory th2 cytokines (including interleukin [il]-4, il-5 and il-13), increase in expression of skin barrier proteins related to keratinocyte differentiation, including filaggrin, loricrin, and involucrin, and antioxidant activity6–10 (figure 1) figure 1. potential mechanisms of action of tapinarof in atopic dermatitis *demonstrated in vitro. †demonstrated in mouse models. ‡demonstrated ex vivo. ahr, aryl hydrocarbon receptor; arnt, aryl hydrocarbon receptor nuclear translocator; il, interleukin; nrf2, nuclear factor erythroid 2-related factor 2; ros, reactive oxygen species; tap, tapinarof. ■ tapinarof cream 1% once daily (qd) demonstrated significant efficacy versus vehicle at 12 weeks and was well tolerated in adolescents and adults with moderate to severe ad in a phase 2b trial (nct02564055). efficacy was generally maintained through the last study visit, 4 weeks after completing treatment, warranting further investigation of a potential remittive effect; this will be defined as the maintenance of disease control (a validated investigator global assessment for atopic dermatitis™[viga-ad™] score of 0 [clear] or 1 [almost clear]) off therapy11,12 objective ■ to assess the efficacy and safety of tapinarof cream 1% qd in children and adults with moderate to severe ad in the two pivotal phase 3 studies (adoring 1 and 2) and a longterm extension phase 3 trial (adoring 3) methods trial design: adoring 1 and 2 ■ adoring 1 and adoring 2 are two identically designed, phase 3, multicenter (us and canada), double-blind, vehicle-controlled randomized trials (figure 2) ■ following a 30-day screening period, patients aged ≥2 years old with an viga-ad score ≥3 (moderate to severe) and a percentage body surface area (%bsa) affected of ≥5–≤35% will be randomized 2:1 to tapinarof cream 1% qd or vehicle qd for 8 weeks figure 2. trial design: adoring 1 and adoring 2 trial design: adoring 3 ■ adoring 3 is a long-term, open-label, multicenter extension trial to evaluate the long-term safety and efficacy of tapinarof 1% qd in patients with ad (figure 3) ■ eligible patients completing adoring 1, adoring 2, or the maximal use pharmacokinetics trial can enroll in adoring 3 ■ in addition, approximately 125 pediatric patients (aged 2 to <18 years) can enroll directly in adoring 3 if they had a viga-ad score of ≥3 (moderate) and %bsa affected ≥40% at screening and baseline (pre-randomization), or patients with a viga-ad score of 2 (mild) at screening and baseline (prerandomization) regardless of %bsa affected, and were thus not eligible for participation in the adoring 1 and 2 pivotal trials figure 3. trial design: adoring 3 ■ in adoring 3, patients will be treated based on their viga-ad score: – patients entering with, or achieving, a viga-ad score of 0 (clear) will discontinue treatment and will be monitored for remittive effect, defined as off therapy maintenance of a viga-ad score of 0 (clear) or 1 (almost clear) – patients entering with a viga-ad score ≥1 (almost clear) will receive tapinarof 1% qd until they achieve complete disease clearance, defined as a viga-ad score of 0 (clear) methods (continued) trial design: adoring 3 (continued) – if disease worsening occurs (defined as a viga-ad score ≥2 [mild]), tapinarof 1% qd will be started and continued until a viga-ad score of 0 (clear) is achieved ■ treatment and re-treatment will continue until the end of the study endpoints and statistical analysis: adoring 3 ■ safety and tolerability endpoints: adverse events, patientand investigator-assessed local tolerability, laboratory values, vital signs, and physical exams ■ efficacy endpoints include: – complete disease clearance: proportion of patients achieving viga-ad of 0 (clear) – remittive effect: duration of efficacy maintenance, viga-ad of 0 (clear) or 1 (almost clear) while off therapy, after achieving complete disease clearance (viga-ad=0) – response: proportion of patients who enter the trial with a viga-ad≥2 (mild) and achieve a viga-ad of 0 (clear) or almost clear (1) – durability of response (absence of tachyphylaxis on therapy): maintenance of efficacy on treatment ■ efficacy endpoints will be based on the itt population using observed case and last observation carried forward analyses. safety endpoint analysis will be based on the itt population conclusions ■ this comprehensive phase 3 clinical trial program will assess the efficacy, safety, tolerability, durability, and potential remittive effect of tapinarof cream 1% qd for the treatment of moderate to severe ad in patients down to 2 years of age references 1. weidinger s & novak n. lancet. 2016;387:1109–1122; 2. bieber t. n engl j med. 2008;358:1483–1494; 3. carroll cl, et al. pediatr dermatol. 2005;22:192–199; 4. lewis-jones s. int j clin pract. 2006;60:984–992; 5. national eczema association. https://nationaleczema.org/research/eczema-facts/. accessed may 2021; 6. bissonnette r, et al. j am acad dermatol. 2021;84:1059–1067; 7. dermavant dof [dmvt-505 th2 polarization; apr 2015]; 8. dermavant dof [dmvt-505 ad mouse model; oct 2016]; 9. smith sh, et al. j invest dermatol. 2017;137:2110–2119; 10. kim be, et al. allergy asthma immunol res. 2018;10:207–215; 11. peppers j, et al. j am acad dermatol. 2019;80:89–98; 12. paller a, et al. j am acad dermatol. 2021;84:632–638. acknowledgments the adoring clinical program is funded by dermavant sciences, inc. l.f.e. has served as a consultant/adviser/investigator for almirall, amgen, arcutis, arena, dermavant sciences inc., dermira, eli lilly, forté, galderma, glenmark/ichnos, incyte, leo pharma, novartis, ortho dermatologics, pfizer, regeneron, sanofi genzyme. j.i.s. has received honoraria/grants, and/or has served as a consultant/ advisory board member/speaker for afyx, aobiome, arena, asana, biomx, bluefin biomedicine, bodewell, boehringer-ingelheim, celgene, dermavant sciences inc., dermira, eli lilly, galderma, glaxosmithkline, incyte, kiniksa, leo pharma, luna, menlo, novartis, pfizer, rapt, regeneron, sanofi genzyme. r.b. has served as a consultant/advisory board member/speaker/investigator, and/or receives honoraria/ grant from almirall, amgen, anaptysbio, arcutis, arena pharma, aristea, asana biosciences, bausch health, bellus health, bluefin biomedicine, boehringeringelheim, bristol-myers squibb, cara, dermavant sciences inc., eli lilly, emd serono, escalier, evidera, galderma, gsk, inmagene bio, incyte, janssen, kiniksa, kyowa kirin, leo pharma, nimbus, novan, pfizer, ralexar, rapt, regeneron, respivant, sanofi genzyme, sienna, target rwe, ucb. r.b. is an employee and shareholder of innovaderm research. a.m.t, p.m.b, d.s.r, s.c.p, and j.e.t. are employees of dermavant sciences inc., with stock options. editorial and medical writing support under the guidance of the authors was provided by apothecom, uk, and was funded by dermavant sciences, inc. in accordance with good publication practice (gpp3) guidelines (ann intern med. 2015;163:461–464). contact dr lawrence f. eichenfield at leichenfield@rchsd.org with questions or comments. double-blind treatment (8 weeks) patients with moderate to severe atopic dermatitis (n≈800) ■ aged ≥2 years* ■ viga-ad™ score ≥3† ■ bsa ≥5%–≤35% 2:1 n≈400 tapinarof 1% qdadoring 1 vehicle qd r 2:1 n≈400 tapinarof 1% qdadoring 2 vehicle qd r *a minimum of approximately 15% of patients will be enrolled into each of the following age groups: 2–6 years, 7–11 years, 12–17 years, and ≥18 years. adults (≥18 years) will comprise a maximum of approximately 20% of enrolled patients. †patients with a viga-ad score of 4 (severe) will represent a minimum of approximately 10% of the total randomized population; the remainder of the population will have a viga-ad score of 3 (moderate). prohibited concomitant medications (and washout periods prior to baseline) include monoclonal antibody products approved for ad (4 months), non-topical corticosteroids or immunosuppressants (28 days), and topical pde4 inhibitors, tacrolimus ointment, pimecrolimus cream, medium or high-potency topical corticosteroids or coal tar (all 14 days). bsa, body surface area; viga-ad, validated investigator global assessment for atopic dermatitis™; pde4, phosphodiesterase-4; qd, once daily; r, randomized. statistical analysis ■ efficacy endpoints analyzed from the intention-to-treat (itt) population using multiple imputation for missing data. safety endpoints analyzed based on the safety population, defined as all randomized subjects who receive at least 1 application of study drug ■ for categorical endpoints, p-values for differences between tapinarof cream 1% qd and vehicle calculated using cochran-mantel-haenszel analysis and stratified by baseline viga-ad score and age group. p-values for continuous variables calculated using analysis of covariance, with baseline viga-ad score and age group as covariates and baseline value as a continuous covariate efficacy endpoints ■ primary efficacy endpoint is the proportion of patients with a viga-ad score of 0 (clear) or 1 (almost clear) and ≥2-grade improvement from baseline at week 8 ■ secondary efficacy endpoints from baseline at week 8: – proportion who achieve ≥75% improvement in eczema area and severity index (easi75) – mean change in %bsa affected – proportion who achieve ≥90% improvement in easi (easi90) – proportion of patients aged ≥12 years with a baseline peak pruritus – numeric rating scale (pp-nrs) score ≥4, who achieve ≥4-point reduction in the pp-nrs safety and tolerability endpoints ■ incidence, frequency and nature of treatment-emergent adverse events and serious adverse events ■ laboratory values, vital signs, and electrocardiograms ■ patientand investigator-assessed local tolerability *patients electing not to participate in adoring 3 will attend follow-up visit 1 week after completion of the treatment period in adoring 1 or 2. †patients with a viga-ad score of ≥3 (moderate) and %bsa affected ≥40% at screening and baseline (pre-randomization), or patients with a viga-ad score of 2 (mild) at screening and baseline (pre-randomization) regardless of %bsa affected, who were screened for adoring 1 or 2 but did not meet viga-ad and/or bsa requirements. %bsa, percentage body surface area; viga-ad, validated investigator global assessment for atopic dermatitis™; pk, pharmacokinetics; qd, once daily. ■ eligible patients from adoring 1 and adoring 2* ■ eligible patients from maximal use pk trial ~125 additional patients aged 2 to <18 years enrolling directly into adoring 3† adoring 3 long-term open-label extension (48 weeks) follow-up (1 week) off treatment off treatment viga-ad=0 viga-ad≥1 viga-ad=0 stop treatment tapinarof 1% qd viga-ad≥2 re-start treatment n=up to ~960 skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 41 research letter regional variation in dlqi 0/1 within the corevitas psoriasis registry 6-months following biologic initiation clinton w. enos, md, ms1, katie a. o’connell, ms1, ryan w. harrison, ms2, robert r mclean, dsc, mph2, blessing dube, mph2, abby s. van voorhees, md1 1 eastern virginia medical school department of dermatology, norfolk, va 2 corevitas, llc, waltham, ma recently, we identified geographic variation in treatment patterns and outcomes among psoriasis patients across the united states (us) enrolled in the corevitas psoriasis registry.1 as there is a predictive correlation between reductions in psoriasis area severity index (pasi) and the dermatology life quality index (dlqi) scores among psoriasis patients treated in clinical trials with biologics,2 we assessed for geographic differences in achieving dlqi 0/1 among us patients initiating a biologic therapy in 2018 in the corevitas psoriasis registry, a multicenter registry of psoriasis patients under the care of a dermatologist. informed consent of human subjects was obtained. there were 737 new biologic initiations (mean age 50.3 years, 48.0% women) in 2018 occurring at a corevitas visit that had a subsequent 6-month follow-up, 644 of whom had dlqi > 0 at baseline.1 baseline mean dlqi scores did not vary significantly among geographic regions, p=0.072 (table i). overall, 42.7% of patients achieved dlqi 0/1 at 6-months. the pacific region reported the smallest proportion achieving this target (26.9%) followed by the east south central (esc) (34.3%) and west south central (wsc) (40.9%) with a range of 26.9-51.1% across all regions (p=0.005). in logistic regression models adjusted for age, sex, race, and bmi, the pacific had 61% lower odds of achieving dlqi 0/1 compared to the northeast (odds ratio 0.39, 95% ci: 0.210.71) (table i). in analyses stratified by biologic therapy class, patients in the pacific and the esc were less likely to achieve dlqi 0/1 compared to the northeast among il12/23 & il-23 inhibitor initiators (or 0.23, 95% ci: 0.08-0.65 and 0.23, 95% ci: 0.070.76, respectively) (table ii). as patient-reported-outcomes become more commonplace, consistent monitoring of dlqi will be increasingly important. in a number of countries, dlqi is now part of reimbursement eligibility criteria.3 previous work has shown that dlqi scores are directly associated with measures of disease severity and parallel treatment response.2 our prior study found that patients in the esc, wsc, and pacific regions were less likely to achieve pasi75 compared to the northeast (the region with the greatest proportion of patients achieving treatment targets).1 these geographic regions also had the lowest proportion of patients achieving dlqi 0/1 at the 6-month follow-up visit, consistent with prior observed correlations between these outcome skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 42 table 1. baseline dlqi and odds ratios (95% ci) for achieving dlqi0/1 response at 6-months follow-up by us census region in the corrona psoriasis registry, 2018 region dlqi at baseline1 dlqi0/1 response at 6-months mean (sd) median (q1, q3) % (responders/total) adjusted or (95% ci)2 northeast 8.1 (6.2) 6.0 (3.0, 12.0) 45.7 (90/197) ref pacific 9.0 (5.6) 9.0 (4.0, 14.0) 26.9 (25/93) 0.39 (0.21, 0.71)** mountain/west north central 6.9 (5.6) 5.5 (2.2, 10.8) 49.4 (39/79) 1.15 (0.68, 1.96) west south central 8.7 (5.8) 8.0 (4.0, 12.0) 40.9 (18/44) 0.92 (0.47, 1.82) east north central 7.1 (5.6) 5.5 (2.0, 11.0) 51.1 (24/47) 1.26 (0.64, 2.47) east south central 7.5 (6.0) 6.5 (3.0, 11.0) 34.3 (34/99) 0.71 (0.42, 1.19) south atlantic 7.2 (5.8) 5.5 (3.0, 10.0) 52.9 (45/85) 1.47 (0.86, 2.51) overall 7.8 (5.9) 7.0 (3.0, 12.0) 42.7 (275/644) - 1 p-value = 0.072 from kruskal-wallis test. 2or (95% ci) from multivariable logistic regression adjusted for age, sex, race, bmi, and baseline bsa. generalized estimating equation (gee) were used to account for clustering. **significant at p<0.01 table 2. odd ratios (95% ci) for achieving dlqi response 6-months following biologic initiation for us census regions in the corrona psoriasis registry in 2018, stratified by biologic class tnfi il-17i il-12/23i+il-23i region % (responders/t otal) adjusted or (95% ci)1 % (responders/t otal) adjusted or (95% ci)1 % (responders/t otal) adjusted or (95% ci)1 northeast 35.3 (6/17) ref 35.6 (26/73) ref 54.2 (58/107) ref pacific 29.2 (7/24) 0.79 (0.17, 3.61) 24.4 (11/45) 0.47 (0.18, 1.21) 23.1 (6/26) 0.23 (0.08, 0.65) mountain/ west north central 45.5 (10/22) 1.14 (0.28, 4.56) 60.6 (20/33) 2.38 (1.00, 5.70) 37.5 (9/24) 0.60 (0.23, 1.57) west south central 50.0 (3/6) 1.22 (0.16, 9.57) 47.1 (8/17) 1.76 (0.58, 5.34) 33.3 (7/21) 0.53 (0.19, 1.46) east north central 62.5 (5/8) 2.09 (0.32, 13.54) 57.1 (12/21) 2.40 (0.87, 6.64) 38.9 (7/18) 0.52 (0.18, 1.49) east south central 30.0 (6/20) 0.68 (0.16, 2.96) 40.7 (24/59) 1.39 (0.66, 2.90) 20.0 (4/20) 0.23 (0.07, 0.76) south atlantic 28.6 (4/14) 0.61 (0.12, 3.01) 55.0 (22/40) 2.11 (0.95, 4.71) 61.3 (19/31) 1.54 (0.65, 3.64) 1or (95% ci) from multivariable logistic regression adjusted for age, sex, race, bmi, and baseline bsa. firth adjustments were utilized to address quasi-separation. measures.2 yet, after controlling for age, sex, race, and bmi, only the pacific was statistically significantly less likely to achieve dlqi 0/1. reasons for inconsistency among the pacific, esc, and wsc with respect to odds of achieving dlqi 0/1 are not yet known. we suspect several variables may contribute, including genetic heterogeneity or skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 43 lifestyle characteristics not captured as part of the registry. limitations of this study include that the corevitas registry is not a random, population-based, representative sample. the impact of seasonal/climate related variables, genetic heterogeneity, and dietary factors were not considered in this analysis. when analyzing outcomes by drug class in the fully adjusted model, sample sizes were small and therefore need to be interpreted with caution. despite these, with the use of real-world data, we show that improvement of dlqi scores at 6-months of treatment for psoriasis is not geographically uniform across the us. regions that had the lowest proportions of achieving pasi751 also had the lowest proportions of patients achieving dlqi 0/1; yet when fully adjusted only patients in the pacific region were less likely to achieve dlqi 0/1, suggesting factors beyond treatment response impact patient quality of life. acknowledgements: the authors thank the participating providers and patients for contributing data to the corevitas psoriasis registry. this study was supported through a partnership between the corevitas psoriasis registry and the national psoriasis foundation medical board. conflict of interest disclosures: abby s. van voorhees, md receives grant/research support from celgene, lilly, abbvie; consultant: amgen, bms, boehringer ingelheim, ucb funding: this study was sponsored by corevitas, llc (formerly corevitas) and the analysis was funded by corevitas llc. access to study data was limited to corevitas and corevitas statisticians completed all of the analysis; all authors contributed to the interpretation of the results. corevitas has been supported through contracted subscriptions in the last two years by abbvie, amgen, boehringer ingelheim, bristol-myers squibb, celgene, chugai, eli lilly and company, genentech, gilead, janssen, novartis, ortho dermatologics, pfizer inc., regeneron, sanofi, sun and ucb. corresponding author: abby s. van voorhees, md eastern virginia medical school department of dermatology 721 fairfax avenue suite 200, andrews hall norfolk, va 23507 phone: 757-446-5629 fax: 757-446-6000 email: vanvooas@evms.edu references: 1. enos cw, o’connell ka, harrison rw, mclean rr, dube b, van voorhees as. psoriasis severity, comorbidities and treatment response differ among geographic regions in the united states. under review at: jid innovations. 2. mattei pl, corey kc, kimball ab. psoriasis area severity index (pasi) and the dermatology life quality index (dlqi): the correlation between disease severity and psychological burden in patients treated with biological therapies. j eur acad dermatol venereol. 2014;28(3):333-337. doi:10.1111/jdv.12106 3. poór ak, brodszky v, péntek m, et al. is the dlqi appropriate for medical decisionmaking in psoriasis patients?. arch dermatol res. 2018;310(1):47-55. doi:10.1007/s00403-017-1794-4 4. strober b, greenberg jd, karki c, et al. impact of psoriasis severity on patientreported clinical symptoms, health-related quality of life and work productivity among us patients: real-world data from the corevitas psoriasis registry. bmj open. 2019;9(4):e027535. published 2019 apr 20. doi:10.1136/bmjopen-2018-027535 mailto:vanvooas@evms.edu powerpoint presentation appropriate utilization of the prognostic 40-gene expression profile (40-gep) test for cutaneous squamous cell carcinoma (cscc) demonstrated by clinical reports and physician evaluation of real-world cases acknowledgments & disclosures references › this study was sponsored by castle biosciences, inc. › all authors contributed to and approved the presentation. › js, br, af, sk and rc are employees and shareholders of castle biosciences, inc. 1. karia, et al. jaad 2012 2. cañueto et al. jaad 2019 3. ruiz et al. jama dermatol 2019 4. wysong, et al. jaad 2021 5. ibrahim, et al. future oncology 2021 presented at winter clinical dermatology conference; january 14-19, 2022. aaron s. farberg1, jennifer j. siegel2, briana rackley2, alison l. fitzgerald2, sarah j. kurley2, robert w. cook2 1baylor scott & white health system; 2castle biosciences, inc. for more information: aaron.farberg@gmail.com ›summary metrics from one year of clinical orders of the 40-gep test demonstrate that clinicians are ordering the test for the intended use population ›survey findings revealed that when incorporating 40-gep testing into their decision-making process for high-risk cscc patients, clinicians do so in a risk-aligned manner ›these results indicate that the additional information provided by the 40-gep test can appropriately assist in management decisions when included with traditional risk factor assessment. conclusions methods objective › to evaluate appropriate utilization of the 40-gep via analysis of a clinician survey, in which real-world cases submitted for clinical testing were presented with or without 40-gep test results. › to evaluate demographics of clinicians and usage of the 40-gep test from one year of clinical orders. › six real-world cases, representing the spectrum of those submitted for clinical testing, were presented to 40-gep test users (10+ orders/year minimum), first without 40-gep result (pre-test) and then with 40-gep results (post-test). › clinicians were asked what treatment recommendations they would make for each preand post-test patient case. assessments from the 34 responding clinicians were ordinally scored and compared using wilcoxon rank or kruskal-wallis. › summary metrics on the 2515 samples received during the first year of clinical ordering (august 31, 2020– august 31, 2021) that met clinical testing criteria, including 40% tumor content and sufficient rna, were generated. › the 40-gep class call and patient risk factors were captured by clinical requisition form review. risk factors included lesion located on the h or m area, ≥2cm diameter, poorly defined borders, patient immunosuppression, rapidly growing tumor, site of prior rt or chronic inflammation, history & physicalother factor noted, high-risk subtype, clark level iv, >2mm invasion, poorly differentiated, lvi, pni, invasion beyond the subcutaneous fat. results › clinicopathologic factors for the 6 real-world cases are shown in table 1. clinicians were well-aligned in their pre-test risk strategy levels among the real-world cases, despite randomization prior to presentation to clinicians (figure 1). › post-testing, clinicians’ overall management plan intensity was significantly changed depending on gep prognostic risk (figure 2a). recommendations for specific treatment decisions were altered depending on 40-gep result (figure 2b-d). asterisks indicate significant change from baseline, corrected for familywise error, p<0.016). › 40-gep testing resulted in 68.8% class 1, 28.3% class 2a, 2.9% class 2b primary scc lesions (figure 3a). of the n=2515 samples meeting clinical testing criteria, 98.1% generated successful test results (n=2468 class call; n= 47 multigene failures) (figure 3b). 75.3% of clinically tested samples have 2 or more high risk factors (median = 3, average = 2.8) (figure 3c). the cases submitted for testing align with the intended use population with almost all cases classifying as nccn high or very high risk (figure 3d). synopsis › there has been an unprecedented increase in cscc incidence over the past three decades,1 along with a continued discordance between available staging systems.2,3 › the 40-gep test was developed and validated to augment traditional assessment approaches with the intention to improve risk-directed patient management for high-risk cscc patients with one or more risk factors. › the 40-gep test has shown significant metastatic risk stratification independent of clinicopathologic factors and staging systems using these factors.4,5 figure 1. pre-test overall management intensity by case real-world case clinical impact study case age sex location subtype differentiation additional high-risk factors high 81 ♂ l superior medial forehead nr moderate invasion beyond subcutaneous fat, pni, lvi, ≥2 cm moderate high 86 ♂ r cheek infil poor invasion >2 mm moderate low 75 ♀ r temporal scalp infil poor low.1 75 is* ♂ r mid preauricular cheek acan moderate low.2 69 ♀ r inferior postauricular skin infil moderate lowest 71 ♀ r dorsal hand (rapidly growing) nr moderate pni = perineural invasion; lvi = lymphovascular invasion; nr = not reported; infil = infiltrating; acan = acantholytic *is = immunosuppressed case table 1. clinicopathologic risk factors for six real-world cases high moderate low overall management intensity scan here for more info figure 2. 40-gep impacts clinician management planning in real-world patient scenarios overall management intensity strategya) b) c) d) baseline class 1 class 2a class 2b adjuvant radiation therapy ** ** *** ** **** * * ***** **** *** * ***** **** ** frequency of follow-up (3 years) nodal assessment via imaging * ***** **** *** real-world clinical testing experience 40-gep testing • samples passing quality control and reporting a class call • n=2468 sccs from n=2402 patients • 56 and 5 patients had 2 or 3 lesions tested, respectively. 68.8% class 1 28.3% class 2a 2.9% class 2b primary cscc with qualifying high-risk factor reported figure 3a. molecular risk profile of patients tested during first year of clinical availability of 40-gep figure 3c. most tested patients have 2 or more high risk factors figure 3b. the 40-gep test has high technical reliability figure 3d. clinicopathologic risk group of tested patients 98.1% successful 40-gep 1.9% mgf clinicopathologic risk* % of patients nccn: very high risk 39.3% high risk 60.5% low risk** 0.2% bwh t-stage: t1 38.5% t2a 39.4% t2b 21.6% t3 0.6% *estimated based on factors reported. all reported pni was considered an upstaging factor. for patients with >1 lesion tested, the riskiest lesion is reported here. **all patients designated low risk by nccn presented with infiltrating histopathology. risk factor count per sample n u m b e r o f sa m p le s median = 3 average = 2.8 https://castlebiosciences.com/research-development/publications/ slide number 1 fc21 sb retro poster kirsch sofpironium bromide comparison to glycopyrrolate once in circulation, sofpironium bromide rapidly hydrolyzes into its metabolite (bbi-4010), a less active anticholinergic agent, therefore reducing its potential for side effects anticholinergic medications are useful for the management of primary axillary hyperhidrosis (ahh). however, due to inhibition of cholinergic receptors in tissues other than the targeted sweat glands, the use of both oral and topical anticholinergics for the treatment of ahh often results in systemic side effects, such as dry mouth, blurred vision, mydriasis, and urinary hesitation. sofpironium bromide (sb) is a novel, quaternary ammonium, anticholinergic drug that is a retrometabolically designed structural analogue of glycopyrrolate. unlike glycopyrrolate, sb includes a readily hydrolyzable ester moiety. to obtain this metabolically sensitive site, the “inactive metabolite” approach to retrometabolic drug design was used.1 a hydrolytically sensitive function was introduced in a remote site of the molecule, away from the pharmacophore.2 the molecular structure was further refined based on binding to the relevant muscarinic receptors, and the most potent optical isomer was selected.3 the specific enzyme responsible for hydrolytic metabolism of sb was identified.4 here we review existing pharmacokinetic and pharmacodynamic data for the retrometabolically designed investigational drug sb. binding studies at human muscarinic receptors (m1–m4) and guinea-pig ileum assays have found sb to have potency close to glycopyrrolate with a shorter duration of action.2 the mydriatic effects of sb were compared to those of glycopyrrolate in rabbits,2 where the activity of sb and glycopyrrolate lasted for approximately 48 hours and 144 hours, respectively. in vitro sb half-life in human plasma was short (3.86 hours). in a separate maximum-use pharmacokinetic (pk) study of sb in human subjects with ahh, 3fold supratherapeutic application to the axillae, thighs, and palms had no meaningful impact on systemic exposure compared with the intended therapeutic dose.5 systemic exposure to sb and its major metabolite bbi-4010 was minimal with most samples <1 ng/ml and many results below the limit of quantitation.5 to date, more than 1300 subjects have been exposed to sb across various clinical studies, and <5% subjects have been discontinued due to adverse events. results methods a need exists to find new anticholinergics with maximal therapeutic benefits and minimal systemic side effects for the treatment of ahh. retrometabolic drug design is intended to create drugs with an increased therapeutic index by integrating metabolism considerations into the drug design process.1 sb is an anticholinergic agent synthesized according to the principles of retrometabolic drug design. both nonclinical and clinical studies support the concept that the retrometabolic design of sb may confer certain safety and pk benefits without compromising desired anticholinergic effect. conclusion funding statement references 1 bodor n, buchwald p. retrometabolic drug design and targeting. wiley; 2013. 2 ji f, wu w, dai x, et al. synthesis and pharmacological effects of new, n-substituted soft anticholinergics based on glycopyrrolate. j pharm pharmacol. 2005;57(11):1427-1435. doi:10.1211/jpp.57.11.0008 3 tóth-sarudy e, tóth g, pallagi i, et al. preparation and biological effects of pure stereoisomeric novel soft anticholinergics. pharm. 2006;61(2):90-96. 4 samir a, ohura k, bodor n, imai t. identification of major esterase involved in hydrolysis of soft anticholinergic (2r3’r-sgm) designed from glycopyrrolate in human and rat tissues. j pharm sci. 2019;108(8):2791-2797. doi:10.1016/j.xphs.2019.03.030 5 kirsch b. an open-label, repeat-dose, maximum-use study to evaluate the pharmacokinetics of sofpironium bromide gel, 15% topically applied in subjects with primary axillary hyperhidrosis (study bbi-4000-cl-102). presented at the: fall clinical; november 29, 2020; las vegas, nevada. brickell biotech, inc. supported the study and preparation of this abstract. academic poster presented at the 2021 fall clinical dermatology conference | las vegas, nv | october 21 – october 24, 2021 h2o physiologic conditions no reaction glycopyrrolate sofpironium bromide bbi-4010 h2o physiologic conditions making fresh tracks in dermatology® objective investigating treatment of primary axillary hyperhidrosis with a topical retrometabolic anticholinergic drug nicholas bodor, phd1, adam friedman, md2, stacy smith, md3, james del rosso, md4, janet dubois, md5, adelaide hebert, md6, tory sullivan, md7, zakiya rice, md8, joe gorelick, np9, leon kircik, md10, lawrence green, md2, brandon kirsch, md11, deepak chadha12, ms, mba background 1bodor laboratories, miami, fl, 2george washington university school of medicine, washington, dc, 3california dermatology and clinical research institute, encinitas, ca, 4jdr dermatology research/thomas dermatology, las vegas, nv, 5dermresearch, inc., austin, tx, 6department of dermatology, the university of texas health science center, houston, tx, 7sullivan dermatology, north miami beach, fl, 8department of dermatology, emory university school of medicine, atlanta, ga, 9california skin institute, san jose, ca, usa, 10department of dermatology, icahn school of medicine at mount sinai, new york, new york, 11kirsch dermatology, naples, fl, 12brickell biotech, inc., boulder, co skin july 2021 1243 proof skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 393 research letter dermatology residency applicants’ concerns due to covid-19 kayla a. clark, bs1, virginia m. miori, phd2, virginia a. jones, md, ms1, maria m. tsoukas, md, phd1 1department of dermatology, university of illinois at chicago, chicago, il 2department of decision and system sciences, saint joseph’s university, philadelphia, pa educational policy changes related to the coronavirus disease 2019 (covid-19) pandemic during the 2020-2021 residency application cycle caused challenges for dermatology residency applicants.1 as advised by the association of american medical colleges (aamc), programs conducted interviews entirely virtually.2 due to these unique circumstances, our group created a survey to gain insight into dermatology residency applicants’ concerns attributable to the covid-19 pandemic and to gauge which solutions they proposed. a 24-item, irb-exempt, anonymous, online survey, was distributed to 240 medical students via social media (groupme, twitter, and instagram). eligibility was limited to us md students applying to dermatology residency in the 2020-2021 or 2021-2022 abstract background: the covid-19 pandemic caused substantial disruptions to medical education. we hypothesized that these disruptions may affect students applying to competitive residencies such as dermatology. methods: a 24-question irb-exempt, online, anonymous survey was distributed to 240 eligible medical students via social media to assess dermatology residency applicants’ concerns due to the covid-19 pandemic and to collect student-proposed solutions to assist with the virtual application cycle. eligibility consisted of us md students applying to dermatology residency in the 2020-2021 or 2021-2022 application cycles. statistical significance was calculated using the chi-squared procedure, ttest/anova, mann whitney test, and kruskal-wallis tests with post-hoc tukey and mann whitney tests. results: of 240 eligible students, 77 students attempted the survey whereas 69 students completed it (response rate 32%, completion rate 89%). salient findings include students without home dermatology departments (whd; n=24) who demonstrated concerns about research project changes (p=0.00). students under-represented in medicine (uim; n=34) concerned about lack of in-person interviews (p=0.00; p=0.04). ms3 (n=14), concerned about test cost (p=0.00), and effect on test scores because of covid-19 (p=0.03). whd and uim applicants showed concerns about changes in clinical experiences (p=0.03, p= 0.03, respectively). lastly, whd, uim and ms3 expressed concerns about obtaining quality recommendation letters (p=0.00, p=0.04, and p=0.03, respectively). conclusion: our findings demonstrate the various concerns shared by dermatology residency applicants because of the covid-19 pandemic. the suggested solutions offered by participants in our study can be used to improve processes for candidates in the 2021-2022 residency application cycle. skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 394 application cycles. responses were collected over a two-week period. data analysis was conducted using software (spss, version 27, ibm corp, armonk, ny). numerical values were generated for (1) students with and without home dermatology departments (whd), (2) students who selfidentified as underrepresented in medicine (uim) and non-uim, and (3) medical school class (ms3, ms4 and other) with "no concerns" and "extremely concerned" valued at 1 and 5, respectively. statistical significance was calculated using the chisquared procedure, t-test/anova, mann whitney test, and kruskil wallis tests with post-hoc tukey and mann whitney tests. of 240 eligible students, 77 students attempted the survey whereas 69 students completed it (response rate (rr) 32%, completion rate 89%). statistically significant survey responses and respondent demographics are summarized in table 1 and table 2, respectively. salient findings include whd (n=24), demonstrated concern about research project changes (p=0.00). uim (n=34), had concerns about lack of inperson interviews (p=0.00; p=0.04). ms3 (n=14), concerns about test cost (p=0.00) and believed test scores may be affected by covid-19 (p=0.03). whd and uim applicants showed concerns about changes in clinical experiences (p=0.03, p= 0.03, respectively). whd, uim and ms3 showed concerns about obtaining high-quality letters of recommendation (lor) (p=0.00, p=0.04, and p=0.03, respectively). our findings demonstrate that students had significant concerns regarding the 2020-2021 and 2021-2022 application cycles (table 1). those directly related to the virtual match include concerns of accurate sense of program culture, concerns with acquisition of lors, and concerns of lack of interaction with fellow interviewees. despite these concerns, preliminary data released by the aamc reveals an 8% (661 students vs. 611) increase for md students applying to dermatology residency this cycle.3 preliminary match results indicate a 73.9% (382/517) match rate for pgy-2 position for md seniors in the 2020-2021 cycle compared to the 78.1% (368/471) match rate in the 2019-2020 cycle; an overall 4.2% decrease in the match rate.4,5 consistent with md applicant concerns, this cycle’s virtual match yielded a lower match rate. we believe the student-proposed solutions from our study may serve to mitigate anxiety accompanied with the use of virtual interviews in the upcoming cycle. these solutions include virtual meetings with program leadership and residents, which allow for exposure to the programs culture and virtual mentorship which affords the opportunity to acquire a lor. all student-proposed solutions are summarized in figure 1. furthermore, we believe that interviewed applicants may benefit from optional in-person second look events to gain more insight into the program culture and to interact with fellow candidates. however, programs would have to ensure that this event would have not influence their rank order list. our study is limited by a small cohort size, low rr, and a narrow demographic. however, we hope our proposed solutions will allow programs to adjust for applicants’ concerns in the upcoming cycle. in addition, we continue to advocate for the use of holistic review, emphasis on “distance traveled”, and that programs strive for residency classes that mirror the diverse demographics of the united states. skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 395 table 1. statistically significant survey responses category (n, mean, median) response (n1,n2,n3) p value significant paired comparison (p value) how concerned are you about your usmle step 1 or usmle step 2 ck scores being affected by the covid-19 pandemic? uim (34,2.82,3.00) € non-uim (33,2.09,2.00) no concern (10,16) slightly (3,6) somewhat (11,5) moderately (3,4) extremely (7,2) 0.04₺ ms3 (14,3.36,3.00) ms4 (50,2.22,2.00) other (5,2.00,2.00) no concern (2,24,1) slightly (0,7,3) somewhat (7,8,1) moderately (1,6,0) extremely (4,5,0) 0.02 ꝉ ms3–ms4 (0.01)₺ ms3–other (0.03)₺ how concerned are you about changes in your dermatological clinical experience(s)? uim (34,3.74,4.00) € non-uim (33,3.09,3.00) no concern (1,4) slightly (,5) somewhat (6,13) moderately (9,6) extremely (12,5) 0.03₺ home derm dept (45,3.18,3.00) not home derm dept (24,3.88,4.00) no concern (5,0) slightly (10,2) somewhat (13,6) moderately (6,9) extremely (11,7) 0.03₺ how concerned are you about changes to your research projects? home derm dept (45,2.91,3.00) not home derm dept (24,3.92,4.00) no concern (7,1) slightly (11,2) somewhat (11,3) moderately (11,10) extremely (5,8) 0.00₺ how concerned are you about getting an accurate sense of program culture via virtual interviews? uim (34,4.56,5.00) € non-uim (33,3.94,4.00) no concern (0,0) slightly (0,3) somewhat (2,5) moderately (11,16) extremely (21,9) 0.00₺ uim (34,3.18,3.00) € non-uim (33,2.45,2.00) no concern (4,11) slightly (10,8) 0.04₺ skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 396 how concerned are you about acquiring dermatology specific letters of recommendation? somewhat (7,6) moderately (2,4) extremely (11,4) ms3 (14,3.71,4.00) ms4 (50,2.58,2.00) other (5,3.20,3.00) no concern (1,14,0) slightly (2,14,2) somewhat (4,8,1) moderately (0,7,1) extremely (7,7,1) 0.03 ꝉ ms3–ms4 (0.01)₺ home dern dept (45,2.47,2.00) not home derm dept (24,3.58,4.00) no concern (13,2) slightly (14,4) somewhat (8,5) moderately (4,4) extremely (6,9) 0.00₺ how concerned are you that a virtual visiting dermatology elective may not afford adequate interaction for a strong letter of recommendation? home derm dept (45,3.53,4.00) not home derm dept (24,4.33,5.00) no concern (6,1) slightly (4,1) somewhat (8,2) moderately (14,5) extremely (13,15) 0.01₺ how concerned are you about not having any in-person dermatological conferences or networking events? uim (34,4.24,4.00) € non-uim (33,3.64,4.00) no concern (0,3) slightly (2,2) somewhat (4,9) moderately (12,9) extremely (16,10) 0.04₺ would you be concerned about not being able to interact with other peers interviewing for the same programs as you would have the opportunity during in person interviews? uim (34,3.59,4.00) € non-uim (33,2.91,3.00) no concern (6,2) slightly (1,10) somewhat (5,12) moderately (11,7) extremely (11,2) 0.01₺ are you concerned about not having a home dermatology department? home derm dept (45,n/a,n/a) not home derm dept (24,n/a,n/a) yes (1,24) no (4,0) n/a (40,0) 0.000a are you concerned about the financial burden associated with test cancellations, testing in different states or, testing educational subscription extensions? ms3 (14,n/a,n/a) ms4 (50,n/a,n/a) other (5,n/a,n/a) yes (14,16,4) no (0,23,0) n/a (0,11,1) 0.000a skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 397 which of the following impacts has covid-19 had on your research projects? home derm dept (45,n/a,n/a) not home derm dept (24,n/a,n/a) cancelled/stopped (10,4) delayed (20,19) no significant changes (14,1) expedited completion (1,0) 0.025a ₺ mann whitney nonparametric test for difference of medians (two independent populations) + kruskal-wallis test for difference of medians (more than two independent populations) a chi square test for independence € note: two respondents were excluded from the race analysis because they did not specify their specific race/ethnicity. n= # observations, mean=likert mean, median=likert media table 2. respondent demographics stratified by medical school class ms3 (n=14) ms4 (n=50) other (n=5) * total (n=69) gender female 11 35 3 49 male 3 15 2 20 nonbinary 0 0 0 0 prefer not to answer 0 0 0 0 race or ethnicity native american or alaskan american 0 0 0 0 asian or pacific islander 2 9 1 12 black 8 10 0 18 white 1 14 3 18 hispanic or latinx 2 11 1 14 other † 1 6 0 7 geographic region northeast 4 11 2 17 south 4 15 0 19 west 1 2 1 4 midwest 5 22 2 29 abbreviations and symbols: ms3, third-year medical students; ms4, fourth-year medical students. *students indicated the following, research fellowship, masters programs, and 5th year medical student. † students race or ethnicity included: nigerian american, south asian, arab american, middle eastern, two of the above, and black and white. skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 398 figure 1. suggestions made by medical students for virtual residency cycle support conflict of interest disclosures: none funding: none corresponding author: maria tsoukas, md, phd university of illinois hospital & health sciences 808 s. wood st, chicago, illinois 60612 phone: 312413-7767 email: tsoukasm@uic.edu references: 1. rosman is, schadt cr, samimi ss, rosenbach m. approaching the dermatology residency application process during a pandemic. j am acad dermatol. 2020. 2. dermatology residency program director consensus statement and recommendations regarding the 2020-2021 application cycle. https://studentsresidents.aamc.org/media/9526/download. published 2020. accessed april 12, 2021. 3. association of the american medical colleges. eras statistics. https://www.aamc.org/datareports/interactive-data/eras-statistics-data. published 2020. accessed march 26, 2021. 4. national resident matching program. 2021 main residency match results. https://www.nrmp.org/main-residency-match-data/. published 2021. accessed march 26, 2021. 5. national resident matching program. results and data: 2020 main residency match. https://www.nrmp.org/main-residency-match-data/. published 2020. accessed march 26, 2021. 0 5 10 15 20 25 30 35 40 45 virtual mentorship virtual symposiums virtual research virtual meet w/leadership virtual meet w/residents only holistic review emphasis on d&i what could dermatological programs do to best assist students during this time? ms3 ms4 other immunogenicity of guselkumab among psoriasis patients in voyage 1&2 studies kristian reich,1 april w. armstrong,2 yaowei zhu,3 megan miller,3 yin you,3 yaung-kaung shen,3 ya-wen yang,4 peter foley,5 christopher e. m. griffiths,6 bruce strober 7 1translational research in inflammatory skin diseases, institute for health services research in dermatology and nursing, university medical center hamburg-eppendorf, germany; 2keck school of medicine, university of southern california, los angeles, ca, usa; 3janssen research & development, llc, spring house, pa, usa; 4immunology global medical affairs, janssen pharmaceutical companies of johnson & johnson, horsham, pa, usa; 5university of melbourne, st. vincent’s hospital melbourne and probity medical research, skin health institute, carlton, vic, australia; 6dermatology centre, salford royal hospital, university of manchester, manchester, uk; 7yale university, new haven, ct, usa and central connecticut dermatology research, cromwell, ct, usa   background/objective methods conclusions this poster was supported by janssen research & development, llc • originally presented at eadv’s 30th congress, virtual, september 29-october 2, 2021. presented at the winter clinical dermatology conference hawaii® (wc22), 14th-19th jan 2022. • voyage 1 & 2 were phase 3, randomized, double-blinded, placeboand active comparator-controlled studies of guselkumab (gus) in adult patients with moderate-tosevere plaque psoriasis1,2 • the development of anti-drug antibodies (ada) to biologic agents is a normal immune response but may affect efficacy and/or safety3 • here, we assessed the association between the development of ada to gus and either the extent of clinical response or incidence of injection-site reactions (isrs) through 5 years in the voyage 1 and voyage 2 studies • of all gus-treated patients with evaluable samples, 14.4% (111/770) in voyage 1 and 15.5% (146/943) in voyage 2 were positive for ada through week 264 • in both studies, ada titres were predominantly low, with 82.0% in voyage 1 and 82.2% in voyage 2 having peak titres ≤1:160 • only 5 (4.5%) and 8 (5.5%) ada positive patients in voyage 1 and voyage 2, respectively, were positive for nabs to gus • through the end of the 5-year voyage 1 and voyage 2 studies of gus in psoriasis, 15% of patients had developed ada to gus. of these, 5% had antibodies that were classified as neutralizing, which equates to 0.8% of all gus-treated patients. • the development of ada (or nab) was not associated with either reduced clinical efficacy or increased isr rates. however, these data should be interpreted with caution due to the limited number of patients developing ada/nab and/or experiencing isrs within 5 years of commencing treatment. methods (cont'd) results dbl, database lock; pe, primary endpoint; r, randomization; se, secondary endpoint; q2w, every 2 weeks; q8w, every 8 weeks. *the last dose of guselkumab was administered at week 252; efficacy was evaluated through week 252. †safety was evaluated through week 264. dbl, database lock; nonresponders [nr] <pasi 90; pasi, psoriasis area and severity index; pe, primary endpoint; r, randomization; se, secondary endpoint; responders [r] ≥pasi 90; q2w, every 2 weeks; q8w, every 8 weeks. *upon loss of ≥50% of improvement in pasi achieved at week 28 or at week 72 if prerequisite loss of pasi improvement was not observed, then reinitiate or initiate guselkumab. †the last dose of guselkumab was administered at week 252; efficacy was evaluated through week 252. ‡safety was evaluated through week 264. disclosures references 1. blauvelt a, et al. j am acad dermatol. 2017;76(3):405-17. 2. reich k, et al. j am acad dermatol. 2017;76(3):418-31. 3. tsakok t, et al. j eur acad dermatol venereol. 2021;35(2):329-37. figure 1. voyage 1 study design figure 2. voyage 2 study design kristian reich – served as advisor and/ or paid speaker for and/or participated in clinical trials sponsored by abbvie, almirall, amgen, boehringer ingelheim, bristol myers squibb, celgene, eli lilly, forward pharma, galderma, gilead, janssen-cilag, kyowa kirin, leo, medac, novartis, ocean pharma, pfizer, sanofi, ucb, co-founder of moonlake immunotherapeutics. april w. armstrong research investigator and/or scientific advisor to abbvie, boehringer ingelheim, bms, dermavant, dermira, epi health, incyte, janssen, khk, leo, lilly, modmed, novartis, ortho dermatologics, pfizer, regeneron, sanofi, sun, and ucb. peter foley received grant support from abbvie, amgen, celgene, janssen, leo pharma, lilly, merck, novartis, pfizer, sanofi, and sun pharma. he has served as an investigator for abbvie, akaal, amgen, arcutis, argenx, aslan, astrazeneca, bms, boehringer ingelheim, botanix, celgene, celtaxsys, csl, cutanea, dermira, galderma, genentech, gsk, hexima, janssen, leo pharma, lilly, medimmune, melaseq/geneseq, merck, novartis, pfizer, regeneron pharmaceuticals inc, reistone, roche, sanofi, sun pharma, teva, ucb pharma, and valeant, he has served on advisory boards for abbvie, amgen, bms, boehringer ingelheim, celgene, galderma, gsk, janssen, leo pharma, lilly, mayne pharma, merck, novartis, pfizer, sanofi, sun pharma, ucb pharma, and valeant. he has served as a consultant for bms, galderma, genesiscare, janssen, leo pharma, lilly, mayne pharma, medimmune, novartis, pfizer, roche, ucb pharma, and wintermute. he has received travel grants from abbvie, galderma, janssen, leo pharma, lilly, merck, novartis, pfizer, roche, sun pharma, and sanofi, and has served as a speaker for or received honoraria from abbvie, amgen, celgene, galderma, gsk, janssen, leo pharma, lilly, merck, novartis, pfizer, roche, sanofi, sun pharma, and valeant. christopher e. m. griffiths received honoraria as an advisory board member and/or speaker from abbvie, almirall, bristol myers squibb, eli lilly, galderma, janssen, leo, novartis, pfizer, sun pharma, and ucb pharma and research grants from abbvie, celgene, eli lilly, janssen, leo, novartis, pfizer, and sandoz. bruce strober received honoraria or research grants as a consultant, speaker, and/or investigator for abbvie, almirall, amgen, arcutis, arena, aristea, boehringer ingelheim, bristol myers squibb, cara, celgene, dermavant, dermira, equillium, glaxosmithkline, janssen, leo, eli lilly, meiji seika pharma, mindera, novartis, ortho dermatologics, pfizer, sanofi-genzyme sun pharma, regeneron, and ucb pharma; as scientific director for the corevitas psoriasis registry; and as editor-in-chief at the journal of psoriasis and psoriatic arthritis. yaowei zhu, megan miller, yin you, and yaung-kaung shen are all employees of janssen research & development, llc; and ya-wen yang is an employee of janssen immunology global medical affairs; employees may own stock in johnson & johnson, of which janssen is a subsidiary.. • voyage 1 and voyage 2 were identical through week 24; patients were randomized at baseline as follows (figures 1 and 2): o gus 100 mg administered by subcutaneous (sc) injection at weeks 0, 4, and 12, then every 8 weeks (q8w) o placebo at weeks 0, 4, and 12, followed by gus 100 mg sc at weeks 16 and 20, then q8w o adalimumab 80 mg sc at week 0, 40 mg at week 1, then 40 mg every 2 weeks (q2w) through week 23 • in voyage 1 (figure 1), patients in the adalimumab group continued on adalimumab 40 mg q2w through week 47 and crossed over to receive gus at week 52. all patients entered the open-label gus treatment period during weeks 52-252. • in voyage 2 (figure 2), patients entered a randomized withdrawal and retreatment period from week 28 to 72. patients entered the open-label gus treatment period during weeks 76-252. • venous blood samples were collected at regular visits for the detection of antibodies to gus. the ada were detected using a validated electrochemiluminescence immunoassay (eclia) method. • the incidence and titres of ada to gus were summarized through week 264 for all patients who were treated with at least one dose of gus and had evaluable serum samples following treatment • if a patient had a positive sample at the reference baseline visit, the patient was considered as positive only if the peak titre of the post-gus treatment samples was ≥2-fold higher than that of the reference sample at baseline • serum samples that tested positive for ada to gus were further characterized to determine if the antibodies that had developed could neutralize the biologic activity of gus in vitro (i.e., neutralizing antibodies [nabs] to gus) • the proportions of patients achieving clinical response at week 252 were evaluated by positive/negative ada status • clinical response was defined as achieving ≥90% improvement in the psoriasis area and severity index (nearly complete clearance; pasi 90) or 100% improvement (complete clearance; pasi 100) and as an investigator’s global assessment (iga) score of 0/1 (cleared or minimal) or 0 (cleared) • the proportions of patients experiencing isrs through week 264 were evaluated by positive/negative ada status active-comparator period guselkumab (n=329) placebo (n=174) adalimumab (n=334) guselkumab 100 mg at weeks 0 and 4, then q8w adalimumab 80 mg at week 0, 40 mg at week 1, then q2w weeks 0 4 16 pe se 24 se 48 se 52 252* 264† 5 year dbl guselkumab 100 mg at weeks 16 and 20, then q8w guselkumab 100 mg at week 52, then q8w placebo placebocrossover placebocontrolled open-label guselkumab (n=496) placebo (n=248) adalimumab (n=248) guselkumab 100 mg at weeks 0 and 4, then q8w initiate guselkumab 100 mg weeks 28 and 32, then q8w placebo withdrawal → guselkumab treatment upon loss of responses* placebo withdrawal → guselkumab retreatment upon loss of responses* placebo withdrawal → guselkumab retreatment upon loss of responses* continue guselkumab 100 mg q8w continue guselkumab 100 mg q8w continue guselkumab 100 mg q8w guselkumab 100 mg at weeks 16 and 20, then q8w placebo adalimumab 80 mg at week 0, 40 mg at week 1, then q2w active-comparator period placebocrossover placebocontrolled open-label randomized withdrawal and retreatment weeks 40 16 pe se 24 se 28 10076 252† 264‡ 5 year dbl the proportions of patients who achieved pasi 90, pasi 100, iga 0/1, or iga 0 were not impacted by the development of ada to gus no direct association between the development of ada and development of isrs was apparent through week 264. however, the small number of patients who were ada positive and/or had isrs limits drawing a definitive conclusion. among the 13 patients who were positive for nabs, all maintained iga 0/1 and/or pasi 90 responses; 1 patient experienced a mild isr after developing nabs table 1. proportions of patients with clinical response at week 252 by ada status through 5 years; gus-treated patientsa with samples evaluable for immunogenicity voyage 1 voyage 2 negativeb positivec negativeb positivec efficacy patients treated with gusd 536 101 619 117 pasi 90 445 (83.0) 87 (86.1) 505 (81.7) 94 (80.3) pasi 100 280 (52.2) 57 (56.4) 323 (52.3) 67 (57.3) iga 0/1e 437 (81.5) 89 (88.1) 527 (85.1) 95 (81.2) iga 0e 292 (54.5) 58 (57.4) 337 (54.4) 70 (59.8) data are presented as n (%). ada, anti-drug antibodies; gus, guselkumab; iga , investigator’s global assessment; iga 0, cleared psoriasis; iga 0/1, cleared or minimal psoriasis; pasi, psoriasis area and severity index; pasi 90, nearly complete clearance (≥90% improvement); pasi 100, complete clearance (100% improvement). aincludes patients who received ≥1 dose of gus, including those who crossed over from placebo or adalimumab. bincludes all patients whose last sample was negative and excludes patients who were positive for antibodies to gus through week 264. cincludes all patients who had ≥1 positive sample (treatment-boosted or treatment-induced) at any time after their first gus administration through week 264. dincludes patients who had ≥1 evaluable sample after their first gus administration and for whom efficacy assessments at week 252 were performed. eiga results were not available for 1 patient in voyage 2. table 2. proportions of patients with isrs by ada status through 5 years; gus-treated patientsa with samples evaluable for immunogenicity voyage 1 voyage 2 negativeb positivec negativeb positivec safety patients treated with gusd 659 111 797 146 patients with isrs 33 (5.0) 9 (8.1) 41 (5.1) 15 (10.3) number of gus injections 17578 3158 20760 3832 injections with isrs 66 (0.4) 18 (0.6) 37 (0.2) 50 (1.3) data are presented as n (%). ada, anti-drug antibodies; gus, guselkumab; isrs, injection site reactions. aincludes patients who received ≥1 dose of gus, including those who crossed over from placebo or adalimumab. bincludes all patients whose last sample was negative and excludes patients who were positive for antibodies to gus through week 264. cincludes patients who had ≥1 positive sample at any time after their first gus administration through week 264. dincludes patients who had ≥1 evaluable sample after their first gus administration. skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 339 short communication deaf and hard of hearing patients in dermatology: a call to action anuk burli, bs1, kathryn e. somers, md2, jason m. rotoli, md3 1 university of rochester school of medicine and dentistry, rochester, ny 2 university of rochester department of dermatology, rochester, ny 3 university of rochester department of emergency medicin, rochester, ny deaf and hard of hearing (dhh) patients have reported unsatisfying experiences with the healthcare system due to decreased access to care resulting from discrimination and poor experiences with communication in health care settings1. dermatology has similar obstacles for dhh patients. we discuss factors creating healthcare disparities affecting the dhh population in dermatology. the dhh community is composed of people with a range of hearing loss and communication preferences. some use spoken language and identify themselves as hearing impaired (hi) when hearing loss ensues. others are members of the cultural deaf community, an ethnolinguistic minority community defined by common life experiences and primary language (american sign language) who identify as dhh but not hi. asl interpreter services are not found in many dermatology practices. despite federal mandates requiring interpreters (ie. americans with disabilities act), there are financial barriers that limit a dermatology clinic’s ability to hire an asl interpreter as the cost often exceeds provider reimbursement2. additionally, dermatologists see patients in a shorter time period than pcps and a larger volume of patients in a clinic day3. this disincentivizes dermatologists from seeing deaf asl users with an interpreter as the time needed to involve a third party can limit time with and the total number of patients in a day. furthermore, the covid-19 pandemic has created additional barriers to dermatologic care for the dhh population. in-person dermatology visits are conducted using personal protective equipment (ppe), including a face mask, which impairs communication for dhh patients. for dhh patients, facial coverings block facial expressions (an essential part of asl), lip reading, and reduces a dermatologist’s speaking volume making both visual and audio forms of communications nearly inaccessible4. covid-19 restrictions prevent a family member or friend, who can assist with communication, from joining the visit. telemedicine has been increasingly used during the pandemic, but can increase the challenges facing dhh patients (i.e. poor visual quality, inconsistent wifi connection, etc). finally, health literacy has been linked to healthcare disparities within dermatology. due its visual nature, dermatologic educational/visual aids (pamphlets and emails) can improve health literacy and outcomes for hi/dhh patients5. while there is no universal formula for communication, there are some changes to dermatologic care that can alleviate barriers skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 340 faced by hi/dhh patients. to lessen financial barriers towards hiring asl interpreters, there are cost-saving toolkits dermatologists can use to provide affordable accessible medical care, which connect dermatologists with cost-efficient contractual interpreters6. during the covid-19 pandemic, dermatologists can help aid communication for dhh patients by using a safe'n’ clear mask, which allows hi/dhh patients to read facial expressions and lips to augment communication (figure 1)4. furthermore, dermatology practices should consider granting exceptions for visitors accompanying hi/dhh patients who can aid with communication. figure 1. “safe'n’ clear mask” the dhh community is a vulnerable patient population that requires special accommodations to improve access to care. we hope this short communication will bring awareness to factors that affect hi/dhh patients during the covid-19 pandemic and in the future. conflict of interest disclosures: none funding: none corresponding author: anuk burli, bs 601 elmwood avenue rochester, ny, 14620 email: burlianuk@gmail.com references: 1. preminger je, oxenbøll m, barnett mb et al. perceptions of adults with hearing impairment regarding the promotion of trust in hearing healthcare service delivery. int j audiol. 2015 jan;54(1):20-8 2. barnett, s. studies on health care for deaf patients:. "communication with deaf and hard-of-hearing people: a guide for medical education." acad med. 2002 jul;77(7): 694700. 3. robert s. stern, dermatologists and officebased care of dermatologic disease in the 21st century, journal of investigative dermatology symposium proceedings, volume 9, issue 2, 2004, pages 126-130, issn 1087-0024, https://doi.org/10.1046/j.10870024.2003.09108.x. 4. chang mj, lipner sr. caring for deaf and hard of hearing patients in dermatology during the covid-19 pandemic. dermatol ther. 2020 nov;33(6):e14185. doi: 10.1111/dth.14185. epub 2020 sep 4. 5. dhaliwal, a, et al. “addressing health illiteracy in dermatology: an evidence-based education framework.” journal of academy of the american academy of dermatology , sept. 2018, https://www.jaad.org/article/s01909622(18)30963-0/fulltext. 6. “toolkit for working with the deaf and hardof-hearing.” https://www.rrf.org/wpcontent/uploads/mmw-deaf-universaltoolkit-05-24-12.pdf, 24 may 2012, https://www.rrf.org/wpcontent/uploads/mmw-deaf-universaltoolkit-05-24-12.pdf. skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 186 editorial skin cancer screenings: why are the benefits in question? nicholas brownstone, md1, darrell s. rigel, md, ms,2 1 national society for cutaneous medicine, new york, ny 2 department of dermatology, icahn school of medicine at mount sinai, new york, ny agreement exists that screening to detect early cancer saves lives. screenings for multiple cancers have been shown to result in earlier detection and better outcomes. however, a recent article in jama dermatology and the associated commentaries related to screening for skin cancer have led to a renewed discussion regarding benefits versus hypothetical concerns to these programs1,3. historically, the american academy of dermatology’s national skin cancer screening programs have been a major success. from these screenings that began in 1985, thousands of melanomas have been detected with a lessening of the associated mortality and morbidity4,5. melanoma morbidity and mortality is heavily dependent on tumor stage at diagnosis. therefore, skin cancer screening should have the potential to increase the survivability from melanoma by detecting this cancer at an earlier stage thereby positively impacting prognosis. so why do the benefits of skin cancer screening still remain controversial? 2,3. those opposed to skin cancer screening suggest that it has led to artificial increase in melanoma diagnosis. if screening were actually impacting incidence, one would expect a short-term increase in invasive incidence as some cases would be diagnosed earlier and removed from the “pipeline,” then a decrease would be seen when those cases that were diagnosed earlier would have been diagnosed without screening and then subsequently the incidence slope would return to baseline. the introduction of psa screening in the mid-1980s demonstrated this exact pattern for invasive prostate cancer incidence. in contrast, invasive melanoma incidence continuously increased during the studied period at a constant rate and was not impacted by the introduction of screening (figure 1).5 screening doubters also contend that there is an increased level of anxiety generated by positive findings noted at a screening. in fact, the opposite appears to be true. surveys of those attending screenings consistently show a high level of satisfaction. in addition, 87% of those screened in the aad program that were found to have histologically confirmed melanomas did not have a dermatologist5 suggesting that detection of these cancers would have been materially delayed had the screenings not occurred. studies in skin of color patients demonstrate that their increased melanoma mortality is likely a consequence of a later stage diagnosis6. skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 187 figure 1. impact of screening on incidence for prostate cancer versus melanoma. both screening programs began in the mid-1980s. prostate cancer showed an immediate rise upon implementation of screening as cases were identified earlier and removed from the population, then a drop occurred from as these cases would have been removed at a later date then the increasing trend slope returned to prescreening levels. in contrast, melanoma incidence trends were not impacted by national screening programs. there are additional tangible benefits of screening that should also be recognized. the screening is a “teachable moment” where the individual can learn about the signs early skin cancer, thus adding a lifetime benefit of potential earlier detection themselves and those close to them. we have all had patients referred to us from their family or friends who recognized a spot that turned out to be melanoma. also, these programs have had an impact on the public’s and government’s perception of dermatology as a specialty evolving our image toward being serious physicians caring for patients at risk for serious disease from more than “pimple poppers and filler squirters”. rather than abandoning skin cancer screening which has been suggested by some3 our goal should be making screening more efficient. risk stratification is important, but it already occurs to a large extent when the demographics of aad screening attendees are analyzed.5 a better way to reach this goal may be to integrate new non-invasive technologies (e.g. electronic impedance spectroscopy, gene expression profiling and confocal microscopy) into screening to more accurately pre-biopsy assess melanoma. those who question screening hypothesize that augmenting detection efforts leads to an overdiagnosis of melanoma. the concept of overdiagnosis remains hypothetical, with skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 188 little to no data supporting it. an equally plausible (and more supportable) hypothesis is that melanoma incidence is, in fact, rising. given that the absolute numbers of thick melanomas in the us continues to rise, it may be more appropriate to question overdiagnosis viewpoints7. in addition, the absolute number of persons who die from thin melanomas is greater than for thick melanomas. if we begin to adopt this unsupported idea of “overdiagnosis” of “nonlethal” melanomas, we may miss detecting and treating some early invasive lesions which may lead to increased metastatic disease and death. we always can make processes better and skin cancer screening is no exception. however, for all the enumerated reasons, it is clear that we should continue to keep obtaining the benefits from these important programs. conflict of interest disclosures: none funding: none corresponding author: nicholas brownstone, md melanoma fellow national society for cutaneous medicine new york ny email: nicholas@fred.health references: 1. matsumoto m, wack s, weinstock ma, et al. five-year outcomes of a melanoma screening initiative in a large health care system. jama dermatol. published online april 06, 2022. doi:10.1001/jamadermatol.2022.0253 2. swerlick ra. melanoma screening—intuition and hope are not enough. jama dermatol. published online april 6, 2022. doi:10.1001/jamadermatol.2022.0082 3. kulkarni rp, yu wy, leachman sa. to improve melanoma outcomes, focus on risk stratification, not overdiagnosis. jama dermatol. published online april 6, 2022. doi:10.1001/jamadermatol.2022.0097 4. rigel ds, friedman rj, kopf aw, et al. importance of complete cutaneous examination for the detection of malignant melanoma. j am acad dermatol 1986;14:857-60. 5. geller ag, zi z, sober a, et al. the first 15 years of the american academy of dermatology skin cancer screening programs: 1985-1999. (j am acad dermatol 2003;48:34-41. 6. siegel r, miller k, fuchs h, et al. cancer statistics, 2022. ca cancer j clin 2022;72:7– 33 7. waqas r. shaikh, stephen w. dusza, martin a. weinstock, susan a. oliveria, alan c. geller, allan c. halpern, melanoma thickness and survival trends in the united states, 1989–2009, jnci: journal of the national cancer institute, volume 108, issue 1, january 2016, djv294, https://doi.org/10.1093/jnci/djv294 skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 336 brief article potential neurologic side effects of oral isotretinoin: a case of peripheral neuropathy fahad s. siddiqui, do1, benjamin m. witkoff, do2, brad glick, do3 1 alabama college of osteopathic medicine, dothan, al 2 dermatology residency, larkin community hospital palm springs, hialeah, fl 3 glick skin institute, margate, fl isotretinoin is recognized as one of the most effective treatments available for nodulocystic acne. aside from its effectiveness in treating the acne itself, isotretinoin has also been noted to improve the psychosocial aspects of severe acne including depression, anxiety, and quality of life.1 despite its effectiveness, the drug is publicly known for its association with adverse effects such as xerosis, epistaxis, cheilitis, and myalgias as well as less common side effects like depression, anxiety, insomnia, suicidal ideation, sun sensitivity, vision changes, and hair loss.2 while a variety of side effects have been reported, the potential effect of isotretinoin on the peripheral nervous system remains an area of further investigation. here we present a case of a patient who developed foot drop while being treated with oral isotretinoin. a 14-year-old female with a past medical history of acne, seborrheic dermatitis, atopic dermatitis, and hypertrichosis presented to our dermatology clinic seeking treatment for treatment-resistant acne. over the past three years, the patient had failed sufficient trials of adapalene, clindamycin 1% gel, dapsone 7.5% gel, doxycycline 100mg po qd, spironolactone 25mg po bid, and adapalene/benzoyl peroxide. she was subsequently started on oral isotretinoin. based on her weight of 50.8kg, she was started on 40mg daily and continued this treatment successfully for six months for a total cumulative dosage of 141.7mg/kg. she experienced common side effects such as cheilitis, xerosis, and intermittent headaches without signs of increased intracranial pressure. at a follow-up visit two months following the completion of her treatment course, her father, a physician, mentioned abstract oral isotretinoin is a well-known, effective medication used in the treatment of severe cystic acne. while efficacious, the potential side effects of isotretinoin are often discussed and may cause concern for patients. although most side effects of this medication are mild, other more concerning adverse effects have been reported. of note, isotretinoin has the potential to affect the central nervous system (cns), causing headaches, pseudotumor cerebri, and fetal cns malformations. in contrast, the effects on the peripheral nervous system are not well documented. the objective of this case report is to present an instance of oral isotretinoin leading to foot drop in an adolescent patient. introduction case report skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 337 that her cheilitis and xerosis had resolved. however, he stated that during the end of her treatment course, she developed weakness in her left lower extremity. she was evaluated by a neurologist and was diagnosed with foot drop based on clinical presentation and diagnostic assessment by nerve conduction study. the patient experienced no other neurological symptoms and improved within three months of diagnosis following nerve transposition surgery and six weeks of physical therapy. isotretinoin is a medication well known for both its effectiveness as well as its diverse adverse effect profile. while the most common of these adverse effects impact the skin and mucosal surfaces, others such as insomnia, vision changes, hair loss, and gi upset have also been reported1. the effects of isotretinoin on the central nervous system are well documented and include severe headache and pseudotumor cerebri.3 the potential effects on the peripheral nervous system have not been extensively discussed in detail previously. in contrast to isotretinoin, other vitamin a derivatives such as etretinate and all-trans retinoic acid (atra) have demonstrated multiple documented cases of resulting peripheral neuropathy.4 in the case of etretinate, nerve biopsy has shown a decreased number of myelinated fibers as well as axonal degeneration and abnormal schwann cell complexes.5 yamaji et al. describe a case of multiple mononeuropathies associated with atra use for acute promyelocytic leukemia. after three weeks of atra therapy, the patient complained of diplopia as well as dysesthesia of the dorsum of the left hand and right foot. the patient also showed weakness in these extremities and a decrease in right peroneal nerve conduction velocity and amplitude during electrophysiologic study9. the mechanism by which isotretinoin may cause peripheral neuropathy is still unknown, but aydogan and karli hypothesize that nerve conduction is negatively affected by changes in lipid composition of peripheral nerve membranes secondary to isotretinoin therapy.4 additionally, in a study assessing isotretinoin’s effects on action potentials of nerve fibers, it was found that 72% of the 28 patients had significant decreases observed in the mean sensory conduction velocities of median, ulnar, sural, medial plantar, medial dorsal cutaneous, and dorsal sural nerves 6 months after the onset of treatment.6 in contrast to this study, another small study of 18 patients done by chroni et al. found that the standard dose of 1mg/kg of isotretinoin over a short-term course of 1-3 months did not cause a clinical or subclinical peripheral neuropathy.7 while the sample sizes and dosing regimens of the studies are equal, the duration of the studies differ, suggesting that there is still potential for peripheral neuropathy at longer treatment durations and/or higher cumulative dosages. pritchard et al. describe two cases of guillain-barré syndrome developing in patients taking isotretinoin.8 one case showed undetectable sensory nerve potentials and f waves, while the other showed increased f wave latency. both patients had severe illness and were eventually dependent on ventilatory support. while the authors acknowledged that two cases are not sufficient to make a direct association, they serve as another example of the potential negative effect of isotretinoin on the peripheral nervous system. discussion conclusion skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 338 our case represents an example of isotretinoin’s potential impact on peripheral nerve pathology. while the studies evaluating peripheral neuropathy as a side effect of isotretinoin are limited, there is evidence that peripheral neuropathy is a potential adverse effect of taking isotretinoin. we believe clinicians should be aware of this possible adverse effect when prescribing this drug. further investigation is needed to determine whether or not a direct causation exists and at what treatment duration/cumulative dosage patients may be at risk for developing peripheral neuropathy. conflict of interest disclosures: none funding: none corresponding author: fahad s. siddiqui, do 10407 emerald woods ave. orlando, fl 32836 email: siddiquif@acom.edu references: 1. marron s, tomas-aragones l, & boira s. anxiety, depression, quality of life and patient satisfaction in acne patients treated with oral isotretinoin. acta dermato venereologica, 2013;93(6), 701–706. 2. brzezinski p, borowska k, chiriac a, et al. adverse effects of isotretinoin: a large, retrospective review. dermatologic therapy, 2017;30(4), e12483. 3. bigby m, & stern rs. adverse reactions to isotretinoin. journal of the american academy of dermatology, 1988;18(3), 543– 552. 4. aydogan k, karli n. effects of oral isotretinoin therapy on peripheral nerve functions: a preliminary study. clin exp dermatol. 2007;32(1):81-84. 5. danon mj, carpenter s, weiss v, et al. sensory neuropathy associated long-term etretinate (et) therapy. neurology 1986; 36 (suppl. 1): 321. 6. altun y, inan e. mid-term oral isotretinoin therapy causes a predominantly sensory demyelinating neuropathy. ideggyogy sz. 2019;72(5-6):159-164. 7. chroni e, et al. short‐term oral isotretinoin therapy does not cause clinical or subclinical peripheral neuropathy. jounral of dermatological treatment. 2006; 17(1):6-8. 8. pritchard j, appleton r, howard r, et al. guillain-barré syndrome seen in users of isotretinoin. bmj. 2004;328(7455), 1537. 9. yamaji s, kanamori h, mishima a, et al. alltrans retinoic acid-induced multiple mononeuropathies. am j hematol. 1999 apr;60(4):311. doi: 10.1002/(sici)10968652(199904)60:4<311::aid-ajh11>3.0.co;2r. pmid: 10203107. background/objective low risk of serious infections and infections of interest in psoriasis patients treated with guselkumab for up to 5 years in voyage 1&2 phase 3 trials richard g. langley,1 diamant thaçi,2 andrew blauvelt,3 tsen-fang tsai,4 megan miller,5 jenny yu,5 yaung-kaung shen,5 yin you,5 ya-wen yang,6 kim a. papp,7 luis puig,8 peter foley9 1dalhousie university, halifax, ns, canada, 2university of luebeck, luebeck, germany; 3oregon medical research center, portland, or, usa; 4national taiwan university hospital, taipei, taiwan; 5janssen research & development, llc, spring house/horsham, pa, usa; 6 immunology global medical affairs, janssen pharmaceutical companies of johnson & johnson, horsham, pa, usa; 7k papp clinical research and probity medical research, waterloo, on, canada; 8hospital de la santa creu i sant pau, autonomous university of barcelona, barcelona, spain; 9the university of melbourne, st. vincent’s hospital melbourne and probity medical research, skin health institute, carlton, vic, australia • treatment of psoriasis with immunomodulatory biologics may increase the risk for certain types of infections (eg, candidiasis, herpes zoster)1-3 • guselkumab (gus), a monoclonal antibody targeting the p19 subunit of interleukin-23, is approved for the treatment of moderate to severe psoriasis and active psoriatic arthritis • voyage 1 and 2 were randomized, double-blinded, placebo (pbo)and active-comparator-controlled phase 3 studies that demonstrated the long-term efficacy and safety of gus in patients (pts) with moderate to severe psoriasis4,5 ɤ infection rates were low and comparable across groups during the pboand active-comparator periods of these studies4,5 • this analysis examines the risk of specific infection-related adverse events (aes) in pts treated with gus for up to 5 years using pooled data from voyage 1 and 2 • in both studies: o pts randomized to: – gus 100 mg at week (w)0, w4, then q8w – pbo at w0, w4, and w12, followed by gus 100 mg at w16 and w20, then q8w – adalimumab (ada) 80 mg at w0, 40 mg at w1, then 40 mg q2w through w47 (voyage 1) or w23 (voyage 2) o in voyage 1, all pts entered an open-label gus treatment period during w52-252 o in voyage 2, all pts entered a randomized withdrawal and gus retreatment period from w28-72; pts entered an open-label gus treatment period during w76-252 o the last dose of gus was administered at w252; safety was evaluated through w264 • pooled safety data were analyzed in the gus group (including w16 pbo crossover, n=1221), the ada→gus group (n=500), and the combined gus group (gus and ada→gus groups, n=1721) • infection-related outcomes of interest included cumulative rates per 100 pt-years (py) of overall, serious, and opportunistic infections (including active tuberculosis), along with treatment-emergent aes (teaes) of candida and herpes zoster infections • in 1721 pts with moderate to severe psoriasis who were treated with gus for up to 5 years, observed infection‑related ae patterns were consistent with previously reported shorter‑term safety findings • serious infections and infection‑related teaes of interest were infrequent • these results support gus as a generally well tolerated therapy for the long‑term treatment of pts with moderate to severe plaque psoriasis methods conclusions results of 1721 pts treated with gus, 78.4% (1349/1721) completed treatment with study drug through w252 • total py of follow-up: gus (n=1221), 5254 py; ada→gus (n=500), 1912 py; combined gus (n=1721), 7166 py across groups, the overall rate of infections ranged from 56.8 to 62.0 per 100 py of follow‑up. the most common (≥2.0 per 100 py in any group) types of infections were nasopharyngitis, upper respiratory tract infection (urti), bronchitis, and pharyngitis. • in the combined gus group, there were a total of 8 reported cases of cellulitis, 8 cases of appendicitis, and 7 cases of pneumonia in 7166 py of follow-up • no pt discontinued study drug due to an ae of candida or herpes zoster infection • all events resolved (some without treatment, some with standard topical or oral therapy) • there were no reported opportunistic infections, including no cases of active tuberculosis, among gus-treated pts from w0 to w264 • rates (95% ci) of non-pathogen-specific fungal infections suspicious for candida† were as follows: o gus (n=1221): 0.11 (0.04, 0.25) o ada→gus (n=500): 0.16 (0.03, 0.46) o combined gus (n=1721): 0.13 (0.06, 0.24) incidence rates were low for teaes of interest, including candida and herpes zoster infections across groups, the overall rate of serious infections was low and ranged from 0.52 to 0.97 per 100 py of follow‑up. the most common (≥0.10 per 100 py in any group) types of serious infections were cellulitis, appendicitis, and pneumonia. the most common candida infections were vulvovaginal and skin infections rate (95% ci) per 100 py of teaes of interest* gus (n=1221) ada→gus (n=500) combined gus (n=1721) overall candida infections 0.49 (0.32, 0.73) 0.52 (0.25, 0.96) 0.50 (0.35, 0.70) vulvovaginal candidiasis 0.29 (0.16, 0.47) 0.05 (0.00, 0.29) 0.22 (0.13, 0.36) skin candida 0.11 (0.04, 0.25) 0.37 (0.15, 0.75) 0.18 (0.10, 0.31) oral candidiasis 0.04 (0.00, 0.14) 0.05 (0.00, 0.29) 0.04 (0.01, 0.12) genital candidiasis 0.02 (0.00, 0.11) 0.05 (0.00, 0.29) 0.03 (0.00, 0.10) balanitis candida 0.02 (0.00, 0.11) 0 (0.00, 0.16) 0.01 (0.00, 0.08) candida infection 0.02 (0.00, 0.11) 0 (0.00, 0.16) 0.01 (0.00, 0.08) *search criterion: meddra high-level term, candida infections; preferred terms with rate >0 in any group are shown ada, adalimumab; ci, confidence interval; gus, guselkumab; py, patient-years; teaes, treatment-emergent adverse events referencesdisclosures 1. armstrong aw et al. am j clin dermatol. 2016;17:329-36; 2. shalom g et al. j dermatolog treat. 2019;30:534-9; 3. kalb re et al. jama dermatol. 2015;151:961-9; 4. blauvelt a et al. j am acad dermatol. 2017;76:405-17; 5. reich k et al. j am acad dermatol. 2017;76:418-31. richard g. langley: served and has received compensation in the form of grant funding and/or honoraria as principal investigator for and is on the scientific advisory board or has served as a speaker for abbvie, amgen, boehringer ingelheim, celgene, eli lilly, janssen, leo pharma, merck, novartis, pfizer, sun pharma, and ucb. diamant thaçi: served as a consultant and/or advisor for abbvie, almirall, beiersdorf, inc., boehringer ingelheim, celgene, eli lilly and company, hexal ag, janssen-cilag, leo pharma inc, novartis pharmaceuticals corp., pfizer inc., sandoz biopharmaceuticals, sanofi, and ucb; as a speaker for abbvie, almirall, celgene, eli lilly and company, hexal ag, janssen-cilag, medac pharma, inc, novartis pharmaceuticals corp., pfizer inc., regeneron, sandoz biopharmaceuticals, sanofi, schering-plough corporation, and ucb; and as an investigator for abbvie, celgene, eli lilly and company, glaxosmithkline, janssen-cilag, leo pharma inc, novartis pharmaceuticals corp., parexel, pfizer inc., regeneron, and ucb. andrew blauvelt: served as a scientific adviser and/or clinical study investigator for abbvie, abcentra, aligos, almirall, amgen, arcutis, arena, aslan, athenex, boehringer ingelheim, bristol-myers squibb, dermavant, ecor1, eli lilly and company, evommune, forte, galderma, incyte, janssen, landos, leo, novartis, pfizer, rapt, regeneron, sanofi genzyme, sun pharma, ucb, and vibliome. tsen‑fang tsai: received honoraria from abbvie, eli lilly, janssen, novartis, and pfizer. megan miller, jenny yu, yaung‑kaung shen, yin you: employees of janssen research & development, llc (a subsidiary of johnson & johnson), and own johnson & johnson stock and/or stock options. ya‑wen yang: employee of janssen pharmaceutical companies of johnson & johnson; owns johnson & johnson stock/stock option. kim a. papp: received clinical research grants and/or honoraria as a consultant, and/or speaker, and/or investigator, and/or scientific officer, and/or advisory board member, and/or steering committee member for abbvie, akros, amgen, anacor, arcutis, astellas, avillion, bausch health, valeant, baxalta, boehringer ingelheim, bristol-myers squibb, can-fite biopharma, celgene, coherus, dermavant, dermira, dow pharma, eli lilly, evelo, galapagos, galderma, genentech, gilead, gsk, incyte, janssen, kyowa hakko kirin, leo, medimmune, meiji seika pharma, merck (msd), merckserono, mitsubishi pharma, moberg pharma, novartis, pfizer, prcl research, regeneron, roche, sanofi-aventis/genzyme, sun pharma, takeda and ucb. luis puig: served as a speaker/consultant/advisory board member for and/or received research funding from abbvie, almirall, amgen, baxalta, biogen, bristol myers squibb, boehringer ingelheim, celgene, fresenius-kabi, gebro, janssen, js biocad, leo pharma, lilly, merck-serono, msd, mylan, novartis, pfizer, regeneron, roche, sandoz, samsung-bioepis, sanofi, and ucb. peter foley: received grant support from abbvie, amgen, celgene, janssen, leo pharma, lilly, merck, novartis, pfizer, sanofi, and sun pharma. he has served as an investigator for abbvie, akaal, amgen, arcutis, argenx, aslan, astrazeneca, bms, boehringer ingelheim, botanix, celgene, celtaxsys, csl, cutanea, dermira, galderma, genentech, gsk, hexima, janssen, leo pharma, lilly, medimmune, melaseq/ geneseq, merck, novartis, pfizer, regeneron pharmaceuticals inc, reistone, roche, sanofi, sun pharma, teva, ucb pharma, and valeant, he has served on advisory boards for abbvie, amgen, bms, boehringer ingelheim, celgene, galderma, gsk, janssen, leo pharma, lilly, mayne pharma, merck, novartis, pfizer, sanofi, sun pharma, ucb pharma, and valeant. he has served as a consultant for bms, galderma, genesiscare, janssen, leo pharma, lilly, mayne pharma, medimmune, novartis, pfizer, roche, ucb pharma, and wintermute. he has received travel grants from abbvie, galderma, janssen, leo pharma, lilly, merck, novartis, pfizer, roche, sun pharma, and sanofi, and has served as a speaker for or received honoraria from abbvie, amgen, celgene, galderma, gsk, janssen, leo pharma, lilly, merck, novartis, pfizer, roche, sanofi, sun pharma, and valeant. ada, adalimumab; gus, guselkumab; py, patient-years; urti, upper respiratory tract infection ada, adalimumab; gus, guselkumab; py, patient-years †as determined by diagnosis and location; search criteria included meddra preferred terms of fungal balanitis, genital infection fungal, vulvovaginal mycotic infection, oral fungal infection, tongue fungal infection, oropharyngitis fungal, and fungal esophagitis. only preferred terms matching these search criteria were included in this analysis. *search criterion: meddra high-level term, candida infections ada, adalimumab; gus, guselkumab; py, patient-years this poster was supported by janssen research & development, llc • originally presented at eadv’s 30th congress, virtual, september 29-october 2, 2021. presented at the winter clinical dermatology conference hawaii® (wc22), 14th-19th jan 2022. acknowledgements: medical writing support was provided by prescott medical communications group (chicago, il) with financial support from ortho dermatologics; ortho dermatologics is a division of bausch health us, llc • presented at winter clinical dermatology conference 2022 • january 14-19, 2022 • kauai, hi therapeutic recommendations for the treatment of toenail onychomycosis in the us shari r lipner, md, phd1; warren s joseph, dpm2; tracey c vlahovic, dpm3; richard k scher, md1; phoebe rich, md4; mahmoud ghannoum, phd5; c ralph daniel, md6; boni elewski, md7 1department of dermatology, weill cornell medicine, new york, ny; 2arizona college of podiatric medicine, midwestern university, glendale, az; 3temple university school of podiatric medicine, philadelphia, pa; 4oregon health and science university, portland, or; 5case western reserve university, and university hospitals cleveland medical center, cleveland, oh; 6department of dermatology, university of mississippi medical center, jackson, ms; 7university of alabama at birmingham school of medicine, birmingham, al synopsis � onychomycosis—a fungal infection of the nail bed or plate—affects up to 14% of individuals in north america1,2 � it is undertreated and treatment is challenging as toenail growth can take up to 12 months or more, the nail plate may prevent drug penetration, and disease recurrence is common3-6 � national guidelines and consensus documents on onychomycosis diagnosis and treatment were last published more than 5 years ago in 2014 (british7) and 2015 (canadian1)—around the time that both topical efinaconazole and tavaborole were first approved in the us in 2014 • since then, more clinical data, post hoc analyses, meta-analyses, and fda-approved indications have become available for onychomycosis drugs • as such, updated medical guidance is needed objective and methods � to provide recommendations for the diagnosis and therapeutic treatment of toenail onychomycosis following a roundtable discussion with the authors on march 15, 2021 � included here is a decision tree for choosing appropriate medications based on disease severity and patient characteristics, as well as an example handout intended for patients on best practices to mitigate disease recurrence results diagnosis, testing, and clinical presentation � careful assessment and testing must be performed when diagnosing onychomycosis; nail dystrophy can be induced by other disorders, and many common conditions that can mimic onychomycosis should be ruled out (figure 1) � laboratory testing should also be performed to identify the infecting organism and exclude non-fungal conditions; figure 1 shows common options that are used in conjunction with clinical diagnosis figure 1. differential diagnosis decision tree no yes ≥1 clinical sign(s) of possible onychomycosis? • longitudinal ridging/splitting • onycholysis • subungual hyperkeratosis • nail plate thickening/crumbling • nail discoloration (yellow, brown, black, white) use ≥1 con�rmatory test(s) for onychomycosis: • dermoscopy as a preliminary test to evaluate nail dystrophy/roughness • histopathology (to distinguish other nail diseases, such as psoriasis) • fungal culture • periodic acid-schiff (pas) stain • potassium hydroxide (koh) • polymerase chain reaction (pcr) differential diagnoses that can cause nail deformity: • nail psoriasis • chronic nail trauma/mechanical issues • onychogryphosis • lichen planus • onycholysis • tumor (subungual malignant melanoma, bowen’s disease, �broma, melanoma) • viral warts • chronic dermatitis or paronychia • bacterial infection • subungual exostosis • subungual hematoma unable to con�rm onychomycosis: recheck diagnosis con�rmed onychomycosis: begin treatment (see figure 2) from lipner sr, et al. j drugs dermatol. 2021;20(10): doi:10.36849/jdd.6291. figure 2. decision tree on therapeutic recommendations for the treatment of confirmed onychomycosis population pregnant/lactating adults clinical presentation pediatric aged ≥65 years, concomitant medications, or comorbidities aged <65 years and relatively healthy no current recommendations topical efinaconazole (check entire family for infection) milda topical efinaconazole patients aged ≥65 years,diabetic, peripheral vascular disease, or immunocompromised topical treatmentb + oral terbinafine or oral fluconazole concomitant meds topical treatmentb +/oral terbinafine or oral fluconazole concurrent nail psoriasis treat onychomycosis first by clinical presentation liver/kidney issues topical treatmentb dermatophytomaa topical efinaconazole moderatea topical efinaconazole or oral terbinafine severea oral terbinafine +/ topical treatmentb f ir st -l in e t re a tm e n t (c o -t re a t ti n e a p e d is , a s n e e d e d , i n a ll p a ti e n ts ) patient characteristics these are topline recommendations for treatment. all patient characteristics—including age, disease duration/severity, clinical presentation, concomitant medications, and comorbidities—must be taken into consideration when making treatment decisions, particularly for patients with more complex presentation. for all treatments, check prescribing information for potential drug-drug interactions and contraindications. amild defined as <20% nail involvement; moderate defined as 20%–60% nail involvement, severe defined as >60% nail involvement and/or additional factors (ie, matrix involvement, 3 mm thickness great toenail, >1 great toenail involved, >3-4 toenails involved, total dystrophic nail); dermatophytoma8-10 is a specialized term used by some dermatologists and can be defined as onychomycosis presenting as yellow or white streaks/patches in subungual space. befinaconazole preferred due to higher rates of complete cure and mycologic cure versus other topical treatments. from lipner sr, et al. j drugs dermatol. 2021;20(10): doi:10.36849/jdd.6291. recommended medications � the authors all agreed that treatment should be individualized for each patient based on nail involvement (number, surface area, thickness), infecting organism, patient characteristics (including comorbidities), current medications, biomechanics, cost/availability/accessibility based on insurance, and patient preference � a decision tree to provide practical guidance on therapeutic recommendations in onychomycosis treatment developed by the authors is shown in figure 2 � therapeutic recommendations by drug are also detailed in figure 3 � among oral medications, terbinafine is most commonly used as first-line treatment, followed by fluconazole � among topical products, efinaconazole is ideal as first-line medication in pediatric patients, patients with less severe disease, and those with dermatophytomas � a topical medication was also recommended for use in combination with terbinafine or fluconazole and can be considered as maintenance therapy to prevent relapse � to improve outcomes, concurrent tinea pedis should be treated in all patients receiving topical therapy for onychomycosis patient education � it is important to manage patient expectations when treating onychomycosis: optimal results can take over a year and clinical cure/normal nail appearance may not be possible � patients should also be educated on the high recurrence rates (6.5%–53%)5; as such, regular follow-up visits with patients are recommended (3–6 months after oral or 1 year after topical treatment) � a physical handout (figure 4) should also be provided to patients, explaining follow-up care/maintenance and highlighting that long-term treatment is more than just pharmacologic (eg, personal care, footwear selection/care, laundry) figure 3. therapeutic recommendations by drug +/− + treatment topical monotherapy topical + oral (terbina�ne or �uconazole) oral (+/topical) ideal for the following: • milda or moderatea disease (e�naconazole) • pediatric patients (e�naconazole) • treatment of dermatophytomasa (e�naconazole) • patients with liver/kidney issues • consider for maintenance therapy to prevent relapse (long-term, from once-weekly to once-daily) • moderatea or severea disease (terbina�ne) • fingernail with con�rmed candida albicans infection (�uconazole) • second-line for patients who fail terbina�ne (�uconazole) • patients aged ≥65 years • patients with diabetes • patients with peripheral vascular disease • immunocompromised patients • patients with certain concomitant medications (oral optional) • second-line for patients who fail topical monotherapy these are topline recommendations for treatment. all patient characteristics—including age, disease duration/severity, clinical presentation, concomitant medications, and comorbidities—must be taken into consideration when making treatment decisions, particularly for patients with more complex presentation. for all treatments, check prescribing information for potential drug-drug interactions and contraindications. efinaconazole preferred for topical treatment due to higher rates of complete cure and mycologic cure versus other topical treatments. asee figure 2 footnote for definitions. from lipner sr, et al. j drugs dermatol. 2021;20(10): doi:10.36849/jdd.6291. figure 4. patient education handout when to contact your doctor • if family/household members have athlete’s foot or nail infections, they should seek treatment and take precautions to prevent spread. • if you see signs of athlete’s foot or reinfection of the nail(s), contact your doctor as soon as possible.  • wear properly sized shoes with adequate toe boxes. avoid narrow-toed shoes or high heels. avoid non-breathable athletic shoes. • don’t walk barefoot in public facilities such as pools, spas, locker rooms, showers, or gyms. wear �ip �ops or shower shoes. • when trying on new shoes, always wear socks. • use antifungal spray or powder in your shoes and/or a uv shoe sanitizer everyday. • wear moisture-wicking socks or copper or silver antimicrobial socks. • alternate athletic shoes to allow each pair to dry thoroughly for 2–3 days between uses. • replace athletic shoes after 500 miles of use. • keep nails short and clean. • only visit a licensed manicurist/pedicurist; bring your own tools and clean them. • don’t pick your toenails or scratch your feet with �ngernails. • don’t use the same clippers/�les used on abnormal nails on normal nails. • don’t share personal nail care instruments, soap, or towels. • wash and dry your hands after contact with infected feet or nails. • dry feet thoroughly after washing. • wash towels, socks, and clothes after every use. socks and other contaminated clothing/towels should be washed at 140°f (60°c). what to know about fungal nail infections • nail fungus may be in your shoes, carpet, bathroom, locker rooms, etc. • toenails grow slowly, so improvements could take 1–2 years to be noticeable. • even after the fungus is gone, the affected nail(s) may never look completely normal. • once the fungus is cleared, it can return. use treatment(s) recommended by your doctor and follow the steps below to help prevent new infections: footwear personal care and laundry from lipner sr, et al. j drugs dermatol. 2021;20(10): doi:10.36849/jdd.6291. conclusions � these therapeutic recommendations, based on new clinical data, provide important updates to previous guidelines/consensus documents to assist healthcare practitioners in the diagnosis and treatment of toenail onychomycosis � onychomycosis should be assessed clinically and confirmed with microscopy, histology, and/or culture � terbinafine is the primary choice for oral treatment and efinaconazole 10% for topical � a topical medication was also recommended for use in combination with terbinafine or fluconazole and can be considered as maintenance therapy to prevent relapse � for optimal outcomes, patients should be counseled regarding treatment expectations as well as follow-up care and maintenance post-treatment references 1. gupta ak, paquet m. j cutan med surg. 2015;19(3):260-273. 2. ghannoum ma, hajjeh ra, scher r, et al. j am acad dermatol. 2000;43(4):641-648. 3. rosen t, friedlander sf, kircik l, et al. j drugs dermatol. 2015;14(3):223-233. 4. gupta ak, stec n. f1000res. 2019;8. 5. tosti a, elewski be. skin appendage disord. 2016;2(1-2):83-87. 6. narasimha murthy s, wiskirchen de, bowers cp. j pharm sci. 2007;96(2):305-311. 7. ameen m, lear jt, madan v, et al. br j dermatol. 2014;171(5):937-958. 8. burkhart cn, burkhart cg, gupta ak. j am acad dermatol. 2002;47(4):629-631. 9. roberts dt, evans eg. br j dermatol. 1998;138(1):189-190. 10. wang c, cantrell w, canavan t, elewski b. skin appendage disord. 2019;5(5):304-308. author disclosures shari r lipner has served a consultant for ortho dermatologics, hoth therapeutics, and verrica. warren s joseph has served as consultant and speaker for ortho dermatologics. tracey c vlahovic has served as investigator and speaker for ortho dermatologics. richard k scher has nothing to disclose. phoebe rich has received research and educational grants from abbvie, allergan, anacor pharmaceuticals, boehringer ingelheim, cassiopea, dermira, eli lilly, galderma, janssen ortho inc., kadmon corporation, leo pharma, merck, moberg derma, novartis, pfizer, ranbaxy laboratories limited, sandoz, viamet pharmaceutical inc., innovation pharmaceuticals (cellceutix), and cutanea life sciences. mahmoud ghannoum has acted as a consultant or received contracts from scynexis, inc, bausch & lomb, pfizer, and mycovia. c ralph daniel has provided clinical research support to ortho dermatologics and owns stock in medimetriks pharmaceuticals. boni elewski has provided clinical research support (research funding to university) for abbvie, anaptys-bio, boehringer ingelheim, bristol-myers squibb, celgene, incyte, leo pharma, lilly, merck, menlo, novartis, pfizer, regeneron, sun pharma, ortho dermatologics, vanda; and as consultant (received honorarium) from boehringer ingelheim, bristol meyers squibb, celgene, leo pharma, lilly, menlo, novartis, pfizer, sun pharma, ortho dermatologics, verrica. poster presented at the 36th fall clinical dermatology conference | las vegas, nv | october 12-15, 2017 certolizumab pegol for the treatment of chronic plaque psoriasis: dlqi and wpai patient-reported outcomes from an ongoing phase 3, multicenter, randomized, activeand placebo-controlled study (cimpact) vincent piguet,1 andrew blauvelt,2 daniel burge,3 luke peterson,4 janice drew,3 robert rolleri,4 jolanta węgłowska5 1cardiff university and university hospital of wales, cardiff, uk; 2oregon medical research center, portland, or; 3dermira, inc., menlo park, ca; 4ucb biosciences, inc., raleigh, nc; 5niepubliczny zakład opieki zdrowotnej multimedica, wrocław, poland introduction • psoriasis affects ~3% of adults in the us1,2 and ~2-6% of adults in europe3; onset can begin at any age, though most patients develop the disease in the third decade of life4 • psoriasis can have a significant negative impact on the physical, emotional, psychosocial, and economic well‑being of affected patients5,6 – in the us, over 80% of psoriasis patients report that the disease negatively affects their emotional state and their enjoyment of life6 – over 90% of unemployed us psoriasis patients report not working solely due to psoriasis or psoriatic arthritis, and almost half of working psoriasis patients regularly miss work due to the disease6 – quality of life instruments for psoriasis have been useful to assess the impact of psoriasis on patients lives and well‑being7,8 • certolizumab pegol (czp) is the only pegylated, fc-free, anti-tnf biologic and is currently under investigation for the treatment of moderate-to-severe chronic plaque psoriasis • previously presented data through week 16 of 3 ongoing, randomized, double-blind, placebo‑controlled trials have demonstrated clinically meaningful efficacy and a safety profile consistent with anti‑tnf therapy9,10 • cimpact (nct02346240) is designed to assess the efficacy and safety of treatment with czp compared with placebo and etanercept (etn) in adult patients with moderate-to-severe chronic plaque psoriasis; results of patient-reported outcomes through week 16 for all patients and results through week 48 for patients initially treated with czp are presented here methods study design • cimpact is an ongoing phase 3, randomized, multinational, parallel-group, placeboand active-controlled trial • patients were randomized 3:3:1:3 to czp 400 mg every 2 weeks (q2w), czp 200 mg q2w (after an initial loading dose of 400 mg at weeks 0, 2 and 4), or placebo q2w for 16 weeks or etn twice weekly for 12 weeks (figure 1) • at week 16, czp‑ and etn‑treated pasi 75 responders were re‑randomized and continued for 32 weeks of maintenance treatment: – from czp 400 mg q2w to 400 mg q2w, 200 mg q2w, or placebo q2w – from czp 200 mg q2w to 400 mg every 4 weeks (q4w), 200 mg q2w, or placebo q2w – from etn to czp 200 mg q2w (after loading dose) or placebo q2w • at week 16, placebo‑treated pasi 75 responders continued placebo q2w for 32 weeks of maintenance treatment • at week 16, pasi 75 nonresponders entered an escape arm for treatment with czp 400 mg q2w figure 1. study design 0 randomization re-randomization 16 4840 443212 36week initial treatment period (double-blind) maintenance period (double-blind) 1:3:3:3 < pasi 50 – withdrawn < pasi 75 < pasi 50 – open label treatment < pasi 75 < pasi 75 < pasi 75 placebo q2w placebo q2w czp 400 mg q4w czp 200 mg q2w czp 400 mg q2w escape czp 400 mg q2w ld etn 50 mg bw washout ld czp 200 mg q2w czp 400 mg q2w bw, twice weekly; czp, certolizumab pegol; etn, etanercept; ld, loading dose of czp 400 mg at weeks 0, 2, and 4 or weeks 16, 18, and 20; pasi 50, ≥50% reduction in psoriasis area and severity index (pasi); pasi 75, ≥75% reduction in pasi; q2w, every 2 weeks; q4w, every 4 weeks patients • eligible patients were ≥18 years of age, had moderate‑to‑severe chronic plaque psoriasis for ≥6 months with a baseline psoriasis area and severity index (pasi) ≥12, affected body surface area (bsa) ≥10%, and physician’s global assessment (pga; 5‑point scale) ≥3 • patients had to be candidates for systemic psoriasis therapy, phototherapy, and/or photochemotherapy • patients were excluded if they had erythrodermic, guttate, or generalized pustular forms of psoriasis; previous treatment with czp, etn, or >2 biologics (including anti‑tnf); or history of primary failure to any biologic or secondary failure to >1 biologic patient-reported outcome measures and study assessments • dermatology life quality index (dlqi) – validated, skin disease‑specific questionnaire that assesses how disease symptoms/treatment affect patient health-related quality of life; higher scores indicate lower quality of life (numeric rating scale 0 to 30) • work productivity and activity impairment–specific health problem questionnaire (wpai) – 6‑item, self‑reported survey that covers 4 domains of work/daily activity impairment, including: 1. absenteeism (work time missed) 2. presenteeism (reduced on‑the‑job effectiveness) 3. work productivity loss (overall work impairment) 4. activity impairment (impairment performing regular daily activities) – questions related to the first 3 domains were to be completed only by patients who were employed at the time of the assessment; questions related to the last domain were to be completed by all patients – wpai domain scores are impairment percentages; higher numbers indicate greater impairment and less productivity • assessments at weeks 16 and 48 – change from baseline (cfb) in dlqi – dlqi minimal clinically important difference (mcid; ≥4‑point reduction7) responder rate – dlqi 0/1 (absolute score ≤1) responder rate – cfb in wpai statistical analysis • efficacy analyses at week 16 were performed on the randomized set (all randomized patients) • efficacy analyses at week 48 were performed on the maintenance set (patients completing the week 16 visit with ≥1 efficacy measurement during the maintenance period) • inferential statistics for cfb in dlqi and wpai at week 16 were based on analysis of covariance (ancova) • mean cfb values are presented for continuous variables, and percentages are presented for responder variables • last observation carried forward (locf) imputation was used to impute data for cfb in dlqi (week 16 and 48) and wpai (week 16) • nonresponse imputation was used for dlqi mcid and dlqi 0/1 analyses • week 48 wpai data was assessed based on observed cases results patient disposition, demographics, and baseline characteristics • a total of 167, 165, and 57 patients were randomized to czp 400 mg q2w, czp 200 mg q2w, or placebo, respectively (figure 2) • patient demographics and baseline characteristics were similar between groups (table 1) figure 2. patient disposition completed week 16 placebo n=57 n=55a (96.5%) discontinued 11 adverse event 4 lack of efficacy 1 protocol violation 1 lost to follow-up 2 consent w/d 2 other 1 discontinued 6 adverse event 1 lost to follow-up 1 consent w/d 3 other 1 discontinued 5 adverse event 1 lost to follow-up 2 consent w/d 1 other 1 discontinued 1 other 1 discontinued 2 adverse event 1 consent w/d 1 discontinued 2 lost to follow-up 1 consent w/d 1 discontinued 4 adverse event 2 consent w/d 1 other 1 discontinued 2 consent w/d 1 other 1 discontinued 3 consent w/d 2 other 1 etn n=170 pasi 75 responder and entered maintenance completed week 48 n=44n=22 n=44 czp 200 mg q2w n=165 czp 400 mg q2w n=167 n=159b (93.5%) n=159 (96.4%) n=159 (96.4%) escapec n=53 escapec n=53 escapec n=85 escapec n=85 escapec n=49 escapec n=49 n=43 (97.7%) n=43 (97.7%) n=20 (90.9%) n=20 (90.9%) n=40 (90.9%) n=40 (90.9%) n=23 (92.0%) n=23 (92.0%) n=49 (100%) n=49 (100%) n=50 n=49dn=25 n=162 (97.0%) n=162 (97.0%) escapec n=36 escapec n=36 n=47 (94.0%) n=47 (94.0%) screened n=733 randomized n=559 aplacebo-treated pasi 75 responders at week 16 (n=2) continued placebo betn‑treated pasi 75 responders at week 16 (n=74) were re‑randomized to placebo (n=24) or czp 200 mg q2w (n=50) cpasi 75 nonresponders at week 16 entered the escape arm for treatment with czp 400 mg q2w dtwo patients completed week 16 but did not enter maintenance period (1 loss to follow‑up; 1 consent withdrawn) ■, czp 400 mg q4w; bw, twice per week; czp, certolizumab pegol; etn, etanercept; pasi 75, ≥75% reduction in psoriasis area and severity index; q2w, every 2 weeks; q4w, every 4 weeks; w/d, withdrawn table 1. patient demographics and baseline disease characteristics placebo (n=57) czp 200 mg q2w (n=165) czp 400 mg q2w (n=167) demographics age (years), mean ± sd 46.5 ± 12.5 46.7 ± 13.5 45.4 ± 12.4 male, n (%) 34 (59.6) 113 (68.5) 107 (64.1) white, n (%) 57 (100) 158 (95.8) 162 (97.0) employed, n (%) 49 (86.0) 117 (70.9) 123 (73.7) geographic region, n (%) north america central/eastern europe western europe 10 (17.5) 36 (63.2) 11 (19.3) 26 (15.8) 107 (64.8) 32 (19.4) 27 (16.2) 109 (65.3) 31 (18.6) weight (kg) mean ± sd range 93.7 ± 29.7 55.0 – 198.5 89.7 ± 20.6 49.0 – 171.1 86.3 ± 20.0 41.8 – 152.0 bmi (kg/m2) mean ± sd range 31.2 ± 8.5 19.6 – 57.4 29.8 ± 6.1 18.3 – 53.0 28.9 ± 5.9 15.4 – 45.1 baseline disease characteristics duration of psoriasis at screening (years) mean ± sd range 18.9 ± 12.9 0.8 – 54.6 19.5 ± 13.2 0.5 – 63.7 17.8 ± 11.5 0.5 – 56.9 concurrent psoriatic arthritis, n (%) 12 (21.1) 27 (16.4) 24 (14.4) pasi mean ± sd range 19.1 ± 7.1 12.0 – 43.1 21.4 ± 8.8 12.0 – 55.5 20.8 ± 7.7 12.0 – 58.5 bsa (%), mean ± sd 24.3 ± 13.8 28.1 ± 16.7 27.6 ± 15.3 pga, n (%) 3: moderate 4: severe 40 (70.2) 17 (29.8) 114 (69.1) 51 (30.9) 113 (67.7) 54 (32.3) prior biologic use,a n (%) anti-tnf anti-il17 11 (19.3) 5 ( 8.8) 8 (14.0) 44 (26.7) 4 ( 2.4) 38 (23.0) 48 (28.7) 4 ( 2.4) 35 (21.0) dlqi, mean ± sd 13.2 ± 7.6 12.8 ± 7.0 15.3 ± 7.3 wpai domain scores, mean ± sd absenteeism presenteeism work productivity loss activity impairment 7.0 ± 24.1 18.4 ± 22.9 25.1 ± 29.7 26.1 ± 25.1 9.5 ± 24.9 21.1 ± 24.7 28.6 ± 31.2 29.8 ± 28.8 5.8 ± 16.6 28.4 ± 26.7 31.9 ± 29.5 35.1 ± 26.6 apatients may have had exposure to >1 prior biologic but ≤2 per exclusion criteria bmi, body mass index; bsa, body surface area; czp, certolizumab pegol; dlqi, dermatology life quality index; il, interleukin; pasi, psoriasis area and severity index; pga, physician’s global assessment; q2w, every 2 weeks; sd, standard deviation; tnf, tumor necrosis factor; wpai, work productivity and activity impairment questionnaire‑specific health problem patient-reported outcomes dlqi baseline to week 16 • at week 16, patients treated with czp 400 mg q2w and czp 200 mg q2w demonstrated clinically meaningful improvements in dlqi vs placebo (figure 3) • at week 16, czp-treated patients demonstrated numerically greater improvement in both dlqi mcid (figure 4a) and dlqi 0/1 (figure 4b) responder rates compared with placebo-treated patients; the czp 400 mg q2w group had numerically greater improvement compared with the czp 200 mg q2w group figure 3. dlqi mean scores at baseline and week 16 13.2 12.1 baseline week 16 placebo (n=57) 12.8 4.7 baseline week 16 15.3 4.3 baseline week 16 czp 200 mg q2wa (n=165b) czp 400 mg q2w (n=167) mean cfb -1.1 -8.1** -11.0**18 16 14 12 8 6 4 10 2 0 m ea n s co re **p<0.0001 vs placebo based on adjusted least squares mean difference from an ancova model with treatment group, region, and prior biologic exposure (yes/no) as factors and baseline dlqi score as a covariate using locf imputation aczp 200 mg q2w patients received a loading dose of czp 400 mg at weeks 0, 2, and 4 b1 patient did not have dlqi mean score values ancova, analysis of covariance; cfb, change from baseline; czp, certolizumab pegol; dlqi, dermatology life quality index; locf, last observation carried forward; q2w, every 2 weeks figure 4. dlqi minimal clinically important differencea and dlqi 0/1 responder rates at week 16 29.8% placebo (n=57) 68.5% 83.8% czp 200 mg q2wb (n=165) czp 400 mg q2w (n=167) 10.5% placebo (n=57) 38.2% 46.1% czp 200 mg q2wb (n=165) czp 400 mg q2w (n=167) 100 80 60 40 20 0 r es po nd er r at e (% ) a. dlqi mcid 100 80 60 40 20 0 r es po nd er r at e (% ) b. dlqi 0/1 a≥4‑point reduction from baseline bczp 200 mg q2w patients received a loading dose of czp 400 mg at weeks 0, 2, and 4 based on nonresponse imputation czp, certolizumab pegol; dlqi, dermatology life quality index; locf, last observation carried forward; q2w, every 2 weeks baseline to week 48 • better maintenance of response was observed at week 48 for those patients re‑randomized from czp 400 mg q2w or czp 200 mg q2w to either dose of czp compared with placebo in dlqi (figure 5a), dlqi mcid (figure 5b), and dlqi 0/1 (figure 5c); the greatest responses were noted in subjects treated with czp 400 mg q2w during both the initial and maintenance periods figure 5. dlqi scores and responder rates at week 16 and week 48 1.5 wk 16 5.7 wk 48 placebo 3.3 wk 48 2.6 wk 16 czp 200 mg q2w 2.3 wk 48 2.8 wk 16 czp 400 mg q4w 2.4 wk 16 12.9 wk 48 placebo 3.8 wk 48 2.8 wk 16 czp 200 mg q2w 1.1 wk 48 1.9 wk 16 czp 400 mg q2w 77.3% wk 16 40.9% wk 48 placebo 65.9% wk 48 72.7% wk 16 czp 200 mg q2w 79.5% wk 48 84.1% wk 16 czp 400 mg q4w 72.0% wk 16 32.0% wk 48 placebo 78.0% wk 48 94.0% wk 16 czp 200 mg q2w 95.9% wk 48 98.0% wk 16 czp 400 mg q2w 72.7% wk 16 13.6% wk 48 placebo 54.5% wk 48 47.7% wk 16 czp 200 mg q2w 59.1% wk 48 50.0% wk 16 czp 400 mg q4w 68.0% wk 16 4.0% wk 48 placebo 50.0% wk 48 50.0% wk 16 czp 200 mg q2w 77.6% wk 48 59.2% wk 16 czp 400 mg q2w 18 16 14 12 10 8 6 4 2 0 m ea n s co re a. mean dlqi score 18 16 14 12 10 8 6 4 2 0 m ea n s co re 100 80 60 40 20 0 r es po nd er r at e (% ) b. dlqi minimal clinically important differencea responder rates 100 80 60 40 20 0 r es po nd er r at e (% ) 100 80 60 40 20 0 r es po nd er r at e (% ) c. dlqi 0/1 responder rates 100 80 60 40 20 0 r es po nd er r at e (% ) czp 200 mg q2w czp 200 mg q2w (n=44) czp 400 mg q4w (n=44) placebo q2w (n=22) czp 400 mg q2w czp 200 mg q2w (n=50) czp 400 mg q2w (n=49) placebo q2w (n=25) a≥4‑point reduction from baseline missing data handled using locf imputation and no statistical comparisons were performed at week 48 czp, certolizumab pegol; dlqi, dermatology quality of life index; locf, last observation carried forward; q2w, every 2 weeks; q4w, every 4 weeks wpai baseline to week 16 • as assessed by wpai, patients receiving either czp dose had improvements in absenteeism, presenteeism, work productivity loss, and activity impairment at week 16 (figure 6); greater improvements were generally observed in subjects receiving czp 400 mg q2w baseline to week 48 • patients initially treated with czp and re‑randomized to the same or different dose of czp maintained improvement across wpai domains at week 48 (figure 7) figure 6. mean absolute change from baseline in wpai domain scores at week 16 wpai domains placebo (n=57) czp 200 mg q2wa (n=165) czp 400 mg q2w (n=167) 4.6 -3.3* -1.5* absenteeism 3.5 -10.4* -18.4** presenteeism 7.4 -13.3** -18.3** work productivity loss 2.8 -17.1** -21.4** activity impairment 20 0 -20 -40m ea n a bs ol ut e c ha ng e fr om b as el in e ( im pr ov em en t) n= 49 117 123 49 117 123 49 117 123 57 164 167 *p<0.05, **p<0.0001 vs placebo; p‑values are nominal and are based on adjusted least squares mean difference from an ancova model with treatment group, region, prior biologic exposure (yes/no) as factors and baseline wpai score as a covariate using locf imputation aczp 200 mg q2w patients received a loading dose of czp 400 mg at weeks 0, 2, and 4 ancova, analysis of covariance; czp, certolizumab pegol; locf, last observation carried forward; q2w, every 2 weeks; wpai, work productivity and activity impairment questionnaire‑specific health problem figure 7. mean absolute change from baseline in wpai domain scores at week 48 wpai domains wpai domains 2.6 -2.5 -12.6 absenteeism -5.0 -8.5 -18.5 presenteeism -5.4 -10.9 -28.8 work productivity loss -32.5 -18.9 -21.3 activity impairment 20 0 -20 -40 m ea n a bs ol ut e c ha ng e fr om b as el in e ( im pr ov em en t) czp 200 mg q2w czp 200 mg q2w (n=44) czp 400 mg q4w (n=44) placebo q2w (n=22) czp 400 mg q2w czp 200 mg q2w (n=50) czp 400 mg q2w (n=49) placebo q2w (n=25) 3.1 -4.2 1.5 absenteeism -22.0 -20.7 -26.8 presenteeism -13.0 -22.1 -24.9 work productivity loss -4.7 -24.4 -30.2 activity impairment 20 0 -20 -40 m ea n a bs ol ut e c ha ng e fr om b as el in e ( im pr ov em en t) n= n=6 27 27 6 27 27 6 27 27 12 36 40 10 27 38 10 27 38 10 27 38 15 41 48 statistical comparisons not performed at week 48 based on observed cases czp, certolizumab pegol; q2w, every 2 weeks; q4w, every 4 weeks; wpai, work productivity and activity impairment questionnaire‑specific health problem conclusions • in the initial treatment period, czp-treated patients had clinically meaningful improvements in dlqi, with a greater proportion of subjects achieving dlqi mcid and/or dlqi 0/1 compared with placebo • reduction in impairment while working and in daily activities, as assessed by wpai, were improved in the czp treatment groups at week 16 compared with placebo • improvements in dlqi and wpai were generally maintained through week 48 in all czp maintenance groups – dlqi 0/1 responder rates were maintained or improved throughout the maintenance treatment period – improvement in dlqi 0/1 responder rate and wpai domains was most pronounced in the group that received czp 400 mg q2w in both the initial and maintenance periods • these results indicate that longer‑term treatment with czp has a positive impact on patient quality of life and functioning • given the substantial burden of disease experienced by patients with psoriasis, czp has the potential to be an important new treatment option for patients with moderate-to-severe chronic plaque psoriasis references 1. rachakonda et al. j am acad dermatol. 2014;70(3):512‑6. 2. kurd et al. j am acad dermatol. 2009;60(2):218‑24. 3. danielsen et al. br j dermatol. 2013;168(6):1303‑10. 4. farber et al. dermatologica. 1974;148(1):1‑18. 5. langley et al. ann rheum dis. 2005;64 suppl 2:ii18‑23. 6. armstrong et al. plos one. 2012;7(12):e52935. 7. basra et al. dermatology. 2015;230(1):27‑33. 8. ali et al. br j dermatol. 2017;176(3):577‑93. 9. gottlieb et al. oral presentation at: 75th annual meeting of the american academy of dermatology; march 3-7, 2017; orlando, fl. abstract 5077. 10. lebwohl et al. poster presentation at: 13th annual maui derm for dermatologists; march 20‑24, 2017; maui, hi. abstract 3120. acknowledgements this study and all costs associated with the development of this poster were funded by dermira, inc. dermira and ucb are in a strategic collaboration to evaluate the efficacy and safety of certolizumab pegol in the treatment of moderate‑to‑severe plaque psoriasis. medical writing support was provided by prescott medical communications group (chicago, il). author disclosures vp: consulting honoraria and/or speaker fees: abbvie, almirall, celgene, janssen, novartis, and pfizer. support to vp department: abbvie, almirall, alliance, beiersdorf uk ltd, biotest, celgene, dermal, eli lilly, galderma, genus pharma, globemicro, janssen‑celag, laroche‑posay, l’oreal, leo pharma, meda, msd, novartis, pfizer, samumed, sinclair pharma, spirit, stiefel, thornton ross, typham, ucb. ab: consulting and/or honoraria: abbvie, amgen, boehringer ingelheim, celgene, dermira, inc., genentech, janssen, eli lilly, merck, novartis, pfizer, regeneron, sandoz. db, jd: employees of dermira, inc. lp, rr: employees of ucb biosciences, inc. jw: investigator and/or speaker: amgen, celgene, coherus, dermira, inc., eli lilly, galderma, janssen, leo pharma, merck, pfizer, regeneron, sandoz, ucb. fc17posterdermirapiguetcertolizumabpegol.pdf skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 601 in-depth review light and laser-based treatments for hidradenitis suppurativa: a systematic review ilya m. mukovozov bhsc, msc, md, phd1*, sara mirali bsc, phd2*, sophie khaslavsky bscn3, sunil kalia md, mhsc, faad, frcpc1,4,5 * equal contribution 1 department of dermatology and skin science, university of british columbia, vancouver, bc, canada 2 faculty of medicine, university of toronto, toronto, on, canada 3 vancouver general hospital, vancouver, bc, canada 4 photomedicine institute and centre for clinical epidemiology & evaluation, vancouver coastal health research institute, vancouver, bc, canada 5 british columbia children’s hospital research institute, vancouver, bc, canada hidradenitis suppurativa (hs) is characterized by painful, recurrent papules and nodules occurring mainly in intertriginous areas. the pain, odor, and disfigurement caused by hs significantly impacts patients’ quality of life and is associated with increased rates of anxiety and depression.1-3 moreover, the symptoms of hs can be physically limiting and interfere with employment and personal functioning.4, 5 early diagnosis and management of hs reduces the risk of disease progression.6 treatment for hs are often multimodal and include medical, surgical, and laser and light-based therapies. although treatment with tumor necrosis factor inhibitors, interleukin-1 inhibitors, antibiotics and others have been reported, these abstract background: hidradenitis suppurativa (hs) is characterized by painful, recurrent lesions occurring mainly in intertriginous areas. the pain, odor, and disfigurement caused by hs significantly impacts quality of life and is challenging to treat. a comprehensive systematic review evaluating the use of light and laser-based treatments for hs is lacking. methods: we performed a systematic review by searching cochrane, medline and embase. title, abstract and full text screening, and data abstraction were done in duplicate. results: forty studies met the inclusion criteria, representing a total of 821 patients. included studies were comprised of 5 randomized within-patient controlled trials, 1 randomized controlled trial, and 34 case series. overall, treatments with the most reported cases were laser surgery, photodynamic therapy (pdt), and laser field treatments which showed a response in 80% (n=344/431), 73% (n=122/167) and 71% (n=84/101) of treated patients respectively. the pooled response rate for psoralen plus ultraviolet a was 69% (n=9/13). conclusion: our results suggest that laser surgery using carbon dioxide (co2) laser or a combination of co2 and nd:yag lasers has a moderate response rate for hs with the most reported cases. laser for field treatment and pdt also had moderate response rates with a large number of reported cases. however, extrapolation of these results may be limited due to the majority of the studies being case series, lack of standardized outcomes being assessed, and insufficient long term follow up results. introduction skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 602 treatments may be associated with significant cost, adverse effects, declining efficacy, and possible drug-drug interactions. in practice, patients may express the preference to avoid systemic treatments if possible. light and laser-based management is known to be a safe and effective treatment option for many dermatological conditions. furthermore, light and laser-based treatment provides the advantage of avoiding the adverse effects and drug interactions associated with systemic therapies. light and laser-based treatments commonly employed for hs include psoralen plus ultraviolet a (puva), photodynamic therapy (pdt), neodymiumdoped yttrium aluminum garnet (nd:yag) laser, carbon dioxide (co2) laser, and others7-10. these treatments are thought to reduce hs lesions by debulking tissue and by reducing the amount of hair follicles, sebaceous glands, and bacterial load.11 although laser and light-based treatments for hs have been reported, little is known about their comparative effectiveness. the aim of this systematic review is to summarize outcomes for light and laser-based treatments used for hs, enabling physicians to better predict clinical response. a systematic review of the literature was conducted adhering to prisma reporting guidelines.12 the study protocol was registered in the prospero database (crd42020223612). study eligibility criteria eligibility criteria for this review were: • population: individuals of any age and sex with hs • intervention (exposure): nd:yag laser, pdt, co2 laser, intense pulse light (ipl), puva • comparator: patients with hs not exposed to intervention • outcomes: pain, lesion count, hidradenitis severity score (hss), visual analogue scale (vas), dermatology life quality index (dlqi), recurrence, healing time, physician global assessment (pga), sartorius score, lesion area and severity index (lasi), patient satisfaction, clinical response • study design: cohort, cross-sectional, and case-series literature search and screening medline, embase, the cochrane database of systematic reviews, and pubmed were searched on june 12, 2020 using variations of the keywords “hidradenitis suppurativa” and “light” (tables s1-s4). no date or language restrictions were applied. title, abstract, and full-text screening were conducted by two independent reviewers (i.m., s.m.) using covidence online systematic review software (www.covidence.org). any conflicts between reviewers were resolved by discussion until a consensus was reached. data extraction data extraction was completed by three independent reviewers (i.m., s.m., s.k.) on a standardized extraction form. level of evidence assessment level of evidence was assessed using a modified hierarchy proposed by guyatt and sackett, where: (1) prospective controlled trial; (2) retrospective study or large case series; (3) small case series.13 data synthesis methods http://www.covidence.org/ skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 603 after data collection, we determined that quantitative evidence synthesis was not feasible due to differences between the studies included in our review. specifically, differences in study design, hs severity, heterogeneity in treatment modalities, patient populations, and outcome measurement. instead, our results are presented in narrative form for each outcome study selection our literature search yielded 460 articles, 405 of which were excluded based on title and abstract review (figure 1). of the 55 studies retrieved for full text screening, 15 were excluded. a total of 40 studies were ultimately included in the review, 6 of which were conference abstracts. the included studies were published between 1987 and 2020 and included 5 randomized within-patient controlled trials, 1 randomized controlled trial, and 34 case series (table 1). the majority of studies were conducted in spain (n=7), north america (n=6), united kingdom (n=5), and italy (n=4) (table 1). patient characteristics (age/sex) in total, our pooled analysis includes 821 patients, 87% (n=623/716) females, with mean age of 33 years, ranging from 15 to 73 years of age. targeted phototherapy a total of 22 studies14-35 included in our review reported on targeted phototherapy using lasers and energy-based devices in patients with hs, representing a sample size of 724 patients with a mean age of 37.2 years (range: 14-73), and 76.3% (n=497/651†) were female. overall, targeted phototherapy improved lesions in 77.6% (n=413/532) of hs patients. adverse effects were reported in 22.9% (n=122/532) of treated patients (table 2). co2 co2 laser was employed in 10 studies (n=396), with 78.5% (n=311/396) of patients showing improvement (table 2).15-17, 19-21, 2426, 28 adverse events were reported in 26.2% of cases (n=103/393). all 10 studies found that co2 laser was an effective treatment modality. in a study of 24 patients, lapins et al. showed that co2 laser treatment with healing by secondary intention was safe, beneficial, and rapidly effective with a mean resolution period of 4 weeks. the majority of patients (91.7%, n=22/24) experienced no recurrence in treated areas. overall, all patients reported satisfaction with this treatment modality.24 the treatments were well tolerated in all patients, and average healing time post procedure was 8.8 weeks.21 among patients with recurrent hs, mikkelsen et al. found that co2 laser surgery with healing by secondary intention was effective with high patient satisfaction rates (94.8%, n=55/58). improvement was reported as great in 75.8% (n=44/58) of patients and mild in 19.0% (n=11/58). overall, 91.4% (n=53/58) of patients stated they would recommend the procedure.28 nd:yag four studies consisting of 92 patients reported on the use of nd:yag in hs27, 29, 32, 33. among studies with reported outcomes, 85% (n=30/35) of treated patients showed improvement (table 2) and adverse events were reported in 15% of cases (n=8/53). overall, 3 of the 4 studies found that nd:yag laser results skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 604 figure 1: prisma diagram of study selection process treatment improved hs.27, 32, 33 in a study of 15 hs patients, vossen et al. found that nd:yag for hair removal prevented disease progression. patients reported a decrease in the number of monthly flares and average hs disease severity, as measured by a numerical response scale (nrs), was significantly lower post treatment (nrs 6.4 ± 2.8 vs nrs 3.6 ± 3.5). overall, 67% (n=10/15) of patients recommended the treatment.32 nd:yag/co2 combined two studies combined nd:yag and co2 laser treatment (n=58), with both reporting a benefit in hs (table 3).14, 23 in a study comparing nd:yag laser with combined co2 and nd:yag lasers in 20 patients, combination treatment resulted in better outcomes compared to nd:yag alone (mean improvement in co2 and nd:yag: 90% ± 20.52 vs mean improvement in nd:yag: 70.68% ± 23.55). other lasers two studies (n=31) reported on the use of ‘other’ lasers, including peht (pediatric endoscopic hidradenitis treatment) and diode laser in hs patients.18, 34 collectively, treatment showed improvement in 93.5% (n=29/31) of patients studied. in a study by esposito et al., peht was found to be an effective treatment for hs and patients reported satisfaction with results. recurrence in untreated locations was reported in only 18% (n=2/11) of patients, which were successfully resolved using the same treatment.34 in a study by fabbrocini et al., diode laser reduced sartorius score, improved hiscr, and reduced dlqi. overall, 90% of patients experienced improvement, with 5% (n=1/20) having complete response, 35% (n=7/20) good response, 50% (n=10/20) partial response, ovid embase 419 citations pubmed 177 citations ovid medline 169 citations ebm reviews cochrane database of systematic reviews 29 citations 794 studies imported for screening 334 duplicates removed 460 studies screened 405 studies irrelevant 55 studies assessed for eligibility 15 studies excluded: o 6 duplicates o 2 no outcomes (histology only) o 3 case reports o 4 commentaries 40 studies included id e n ti fi ca ti o n s cr e e n in g e li g ib il it y in cl u d e d skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 605 and 10% (n=2/20) no response. the sartorius score improved from 28.6 ± 13.0 at baseline to 19.8 ± 12.3 post-treatment.18 ipl four studies (n=83) in our review assessed the use of ipl for the treatment of hs. overall, ipl led to improvement in 65% (n=54/83) of patients and adverse events were reported in 25% (n=16/64) (table 2).22, 30, 31, 35 highton et al., reported that ipl treatment resulted in long-term clinical improvement of lesions in 17 hs patients in an intra-individual controlled trial. clinical improvement was also corroborated by independent analysis of clinical photographs and patient reported satisfaction.22 another study of 25 hs patients found that ipl was useful as an adjuvant treatment for hs patients with mild to moderate disease, and 52% (n=13/25) of patients reported reduced disease activity.31 photodynamic therapy (pdt) 17 studies8, 36-51 reported on the use of pdt in patients with hs (n=167). the mean age was 33.3 years (range: 17-62) and 68.9% (n=115/167) were female. overall, pdt was effective in 70.7% (n=118/167) of patients. adverse events were screened for in 38.3% (n=64/167) of the pdt cohort, and were reported in 35.9% (n=23/64). a number of photosensitizers were used in pdt. ten studies (n=121)8, 37, 43-46, 48-51 reported on pdt for hs with the photosensitizer aminolevulinic acid (ala). in this cohort, 78.5% (n=95/121) of treated patients responded. suarez-valladares et al. found that in a series of hs patients treated with intralesional ala-pdt, 76.3% (n=29/38) achieved complete remission.8 in a smaller study of five hurley stage ii or iii hs patients with recalcitrant disease, no significant improvement was seen, despite mild improvements in sartorius score, vas, and dlqi in all patients (mean change from baseline to post-treatment: sartorius = -1.6, vas = -0.3, dlqi = -6.4%). swelling and blistering was present in 40% (n=2/5) of patients after the first treatment for 8-10 days.52 other photosensitizers utilized for pdt in hs include methylene blue, methyl amino levulinate, and tetracycline. overall, four studies consisting of 28 patients were included in this cohort.36, 38, 41, 42 of those that reported individual patient outcomes, 94.4% (n=17/18) of patients reported improvement. adverse effects were screened in 72.2% (n=13/18) of patients and of these, adverse effects were reported in 92.3% (n=12/13). agut-busquet et al. followed 7 hs hurley stage ii and iii patients treated with pdt and methylene blue. pdt and methylene blue treatment improved dlqi and reduced lesion size in 85.7% (n=6/7) of patients after 1 month.36 relapse was reported in 28.6% (n=2/7) at 7 and 12 weeks post-treatment. psoralen plus ultraviolet a (puva) puva to treat hs was examined in a single retrospective chart review.7 a total of 13 patients were treated with a regimen involving a 15 min bath containing 30 ml of 1-2% 8-methoxypsoralen lotion followed by broadband ultraviolet a. treatments were performed twice weekly, with a median of 25 (range: 3–57) treatments. overall, five patients were reported to have ‘clear or near clear’ hs, four patients reached ‘moderate clearance’, and four showed ‘no to minimal’ improvement. overall, bath puva was effective in 69% (n=9/13) of patients in this series and was well tolerated. adverse events were recorded for two patients and included erythema and claustrophobia. skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 606 the studies included in our review reported on patients with both moderate and advanced disease. many of the studies included in our review utilize laser-based treatments for surgery of affected sites in patients with advanced disease resistant to other therapies. our results suggest that laser-based surgery is associated with a moderate response rate based on a large sample of pooled patients. furthermore, many of the studies employing laser devices for surgery of hs lesions included patients with long standing and recalcitrant disease, suggesting that these treatment modalities can be employed an adjuncts with success even in patients with advanced disease. likewise, treatment modalities that utilize laser-based field therapy of affected areas using nd:yag, ipl, or diode laser were associated with a mild response rate based on a large sample of pooled patients. laser field treatments for hs were employed in patients with both early and advanced disease, suggesting that this treatment modality is appropriate both to treat advanced disease and as a prophylactic therapy to target follicular inflammation and prevent disease progression. a number of adverse events were reported in the studies included in our review. overall, pdt was associated with the highest rates of reported adverse events (36%). laser field treatments had less reported adverse events compared to lasers employed for surgical treatment of hs lesions (18% vs 25%). a number of factors may contribute to this observed difference, including differences in study quality and reporting of adverse events, given that only 105 out of 424 patients treated with laser surgery for hs had adverse events recorded. some of the adverse events reported for laser surgery included pain, infection, hypertrophic scaring, contracture and wound dehiscence. side effects associated with pdt included pain, erythema, blistering, burning. bath puva was generally well tolerated, although two patients reported erythema and claustrophobia. collectively, these findings suggest that while light therapy is a moderately effective treatment modality, adverse events are not uncommon, and patients should be counselled on the risks and benefits of light therapy. while the mechanism underlying the effectiveness of light-based treatments for hs are not well understood, several possibilities have been suggested. co2 laser vaporization and excision removes epithelial sinus tracts which may contain debris and bacteria that can lead to relapse.53 nonablative lasers cause thermal damage to the dermis, which may initiate a wound-healing response with upregulation of procollagen mrna, matrix metalloproteinases, and cytokines that contribute to wound healing.54 our study has several limitations. many studies did not report on the side effects of light-based therapies, which restricts our analysis on treatment tolerability. secondly, some studies reported aggregate data and outcomes for individual patients could not be extracted. moreover, different outcome measures were used in the studies included in our review, further challenging comparisons between studies. finally, the majority of the included studies were case series, which limits the generalizability of our analysis. despite these limitations, our review provides important information that must be discussion conclusion skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 607 interpreted in a clinical context. first, lightbased treatments show moderate benefit in both early and advanced disease. second, laser devices and pdt have moderate clearance rates for patients with hs, however access to the technology and impractical treatment delivery (especially with extensive disease) may be a barrier. third, adverse events are not uncommon with light therapy and patients should be counselled on these risks. though randomized control trials would be the ideal way to validate our findings, studies with treatment comparators are needed to further delineate the therapeutic ladder for hs. conflict of interest disclosures: none funding: none corresponding author: ilya m. mukovozov, md, phd skin care centre 835 w 10th ave, vancouver, bc v5z 4e8 phone: (604) 875-5151 email: ilya.mukovozov@alumni.ubc.ca references: 1. esmann s, jemec gb. psychosocial impact of hidradenitis suppurativa: a qualitative study. acta derm venereol. may 2011;91(3):328-32. doi:10.2340/00015555-1082 2. matusiak l, szczech j, bieniek a, nowickasuszko d, szepietowski jc. increased interleukin (il)-17 serum levels in patients with hidradenitis suppurativa: implications for treatment with antiil-17 agents. journal of the american academy of dermatology. apr 2017;76(4):670-675. doi:10.1016/j.jaad.2016.10.042 3. wright s, strunk a, garg a. new onset 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hidradenitis suppurativa co2-laser stripping-secondary intention technique. british journal of dermatology. oct 1994;131(4):551-556. 25. lapins j, sartorius k, emtestam l. scannerassisted carbon dioxide laser surgery: a retrospective follow-up study of patients with hidradenitis suppurativa. j am acad dermatol. aug 2002;47(2):280-5. doi:10.1067/mjd.2002.124601 26. madan v, hindle e, hussain w, august pj. outcomes of treatment of nine cases of recalcitrant severe hidradenitis suppurativa with carbon dioxide laser. british journal of dermatology. dec 2008;159(6):1309-1314. doi:10.1111/j.1365-2133.2008.08932.x 27. mahmoud bh, tierney e, hexsel cl, pui j, ozog dm, hamzavi ih. prospective controlled clinical and histopathologic study of hidradenitis suppurativa treated with the long-pulsed neodymium:yttrium-aluminium-garnet laser. j am acad dermatol. apr 2010;62(4):637-45. doi:10.1016/j.jaad.2009.07.048 28. mikkelsen pr, dufour dn, zarchi k, jemec gbe. recurrence rate and patient satisfaction of co2 laser evaporation of lesions in patients with hidradenitis suppurativa: a retrospective study. dermatologic surgery. feb 2015;41(2):255-260. doi:10.1097/dss.0000000000000264 29. naouri m, maruani a, lagrange s, et al. treatment of hidradenitis suppurativa using a long-pulsed hair removal neodymium:yttriumaluminium-garnet laser: a multicenter, prospective, randomized, intraindividual, comparative trial. j am acad dermatol. jan 2021;84(1):203-205. doi:10.1016/j.jaad.2020.04.117 30. piccolo d, di marcantonio d, crisman g, et al. unconventional use of intense pulsed light. biomed res int. 2014;2014:618206. doi:10.1155/2014/618206 31. riis pt, saunte dm, sigsgaard v, wilken c, jemec gbe. intense pulsed light treatment for patients with hidradenitis suppurativa: beware treatment with resorcinol. journal of dermatological treatment. 2018;29(4):385-387. doi:10.1080/09546634.2017.1387226 32. vossen a, van der zee hh, terian m, van doorn mba, prens ep. laser hair removal alters the disease course in mild hidradenitis suppurativa. journal der deutschen dermatologischen gesellschaft. jul 2018;16(7):901-903. doi:10.1111/ddg.13563 33. xu lsy, wright dr, mahmoud bh, ozog dm, mehregan da, hamzavi ih. histopathologic study of hidradenitis suppurativa following https://dx.doi.org/10.1111/ijd.14075 skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 609 long-pulsed 1064-nm nd:yag laser treatment. archives of dermatology. jan 2011;147(1):21-28. doi:10.1001/archdermatol.2010.245 34. esposito c, del conte f, cerulo m, et al. pediatric endoscopic hidradenitis treatment: a new minimally invasive treatment for pediatric patients with hidradenitis suppurativa. journal of laparoendoscopic & advanced surgical techniques. apr 2020;30(4):464-470. doi:10.1089/lap.2019.0614 35. wilden s, friis m, tuettenberg a, et al. combined treatment of hidradenitis suppurativa with intense pulsed light (ipl) and radiofrequency (rf). journal of dermatological treatment. 2019;((wilden, friis, tuettenberg, staubachrenz, wegner, grabbe, von stebut) department of dermatology, university medical center, johannes gutenberg, university, mainz, germany(von stebut) department of dermatology, faculty of medicine, university of cologne)doi:http://dx.doi.org/10.1080/09546634. 2019.1677842 36. agut-busquet e, romani j, gilaberte y, garciamalinis a, ribera-pibernat m, luelmo j. photodynamic therapy with intralesional methylene blue and a 635 nm light-emitting diode lamp in hidradenitis suppurativa: a retrospective follow-up study in 7 patients and a review of the literature. photochemical & photobiological sciences. 2016;15(8):1020-1028. doi:10.1039/c6pp00082g 37. navarrete ra, nisis ah, cares jp. effectiveness of 5-aminolevulinic acid photodynamic therapy in the treatment of hidradenitis suppurativa: a report of 5 cases. actas dermo-sifiliograficas. jul-aug 2014;105(6):614-617. doi:10.1016/j.ad.2013.10.016 38. belotto ra, tardivo jp, baptista ms, santos re. clinical response of hidradenitis suppurativa to photodynamic therapy using tetracycline and rl50 (r) light source. lasers in surgery and medicine. mar 2013;45:62-63. 39. bu wb, xu xl, wang y, et al. surgery combined with photodynamic therapy for the treatment of hidradenitis suppurativa: a report of 7 cases. photodiagnosis and photodynamic therapy. jun 2017;18:46-49. doi:10.1016/j.pdpdt.2017.01.176 40. calzavara-pinton pg, rossi mt, aronson e, sala r, italian grp photodynamic t. a retrospective analysis of real-life practice of off-label photodynamic therapy using methyl aminolevulinate (mal-pdt) in 20 italian dermatology departments. part 1: inflammatory and aesthetic indications. photochemical & photobiological sciences. 2013;12(1):148-157. doi:10.1039/c2pp25124h 41. fadel ma, tawfik aa. new topical photodynamic therapy for treatment of hidradenitis suppurativa using methylene blue niosomal gel: a singleblind, randomized, comparative study. clinical and experimental dermatology. mar 2015;40(2):116-122. doi:10.1111/ced.12459 42. abstracts of the 8th european hidradenitis suppurativa foundation (ehsf) conference, 6-8 february 2019, wrocław, poland. exp dermatol. feb 2019;28 suppl 2:5-55. doi:10.1111/exd.13893 43. passeron t, khemis a, ortonne jp. pulsed dye laser-mediated photodynamic therapy for acne inversa is not successful: a pilot study on four cases. journal of dermatological treatment. 2009;20(5):297-298. pii 910443295. doi:10.1080/09546630902882063 44. rodriguez-prieto ma, valladares-narganes lm, gonzalez-sixto b, noguerol-cal m. efficacy of intralesional photodynamic therapy for the treatment of hidradenitis suppurativa. journal of the american academy of dermatology. may 2013;68(5):873-875. doi:10.1016/j.jaad.2012.11.030 45. sotiriou e, apalla z, maliamani f, ioannides d. treatment of recalcitrant hidradenitis suppurativa with photodynamic therapy: report of five cases. clin exp dermatol. oct 2009;34(7):e235-6. doi:10.1111/j.1365-2230.2008.03094.x 46. strauss rm, pollock b, stables gi, goulden v, cunliffe wj. photodynamic therapy using aminolaevulinic acid does not lead to clinical improvement in hidradenitis suppurativa. british journal of dermatology. apr 2005;152(4):803804. doi:10.1111/j.1365-2133.2005.06475.x 47. suarez-valladares m, espasandin-arias m, varas-meis e, fernandez-canga p, castineirasgonzalez j, rodriguez-prieto m. effectiveness of intralesional photodynamic therapy in the management of hidradenitis suppurativa. experimental dermatology. may 2018;27:31-32. 48. valladares-narganes lm, rodriguez-prieto ma, blanco-suarez md, rodriguez-lage c, garciadoval i. treatment of hidradenitis suppurativa with intralesional photodynamic therapy using a laser diode attached to an optical cable: a promising new approach. british journal of dermatology. apr 2015;172(4):1136-1139. doi:10.1111/bjd.13385 49. vilarrasa e, bittencourt f, martorell a, puig l. photodynamic therapy in the treatment of moderate-to-severe hidradenitis suppurativa: a report of 28 patients. experimental dermatology. feb 2019;28:49-49. http://dx.doi.org/10.1080/09546634.2019.1677842 http://dx.doi.org/10.1080/09546634.2019.1677842 skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 610 50. zhang ll, wang pr, shi l, et al. topical 5aminolevulinic acid photodynamic therapy improved refractory acne conglobata and perifolliculitis capitis abscedens et suffodiens rather than hidradenitis suppurativa. journal of innovative optical health sciences. jan 2016;9(1)1640002. doi:10.1142/s1793545816400022 51. gold m, bridges tm, bradshaw vl, boring m. ala-pdt and blue light therapy for hidradenitis suppurativa. j drugs dermatol. 2004 jan-feb 2004;3(1 suppl):s32-5. 52. sotiriou e, apalla z, maliamani f, ioannides d. treatment of recalcitrant hidradenitis suppurativa with photodynamic therapy: report of five cases. clinical and experimental dermatology. oct 2009;34(7):e235-e236. doi:10.1111/j.13652230.2008.03094.x 53. lapins j, sartorius k, emtestam l. scannerassisted carbon dioxide laser surgery: a retrospective follow-up study of patients with hidradenitis suppurativa. journal of the american academy of dermatology. aug 2002;47(2):280285. doi:10.1067/mjd.2002.124601 54. orringer js, voorhees jj, hamilton t, et al. dermal matrix remodeling after nonablative laser therapy. j am acad dermatol. nov 2005;53(5):775-82. doi:10.1016/j.jaad.2005.07.052 skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 611 table 1. characteristics of included studies (n=40) author, year location study design, loe intervention n# mean age (±sd/range ) f: m key findings abdel azim, 2018 egypt rct^ (1) nd:yag co2+nd:y ag 20 29.7 (5) 11:9 higher satisfaction and lower recurrence rates using combined co2 and nd:yag agutbusquet, 2016 spain case series (3) pdt 7 28.9 3:4 good results using pdt with intralesional mb andino navarrete, 2014 chile case series (3) pdt 5 26 (5) 4:1 5-ala and 635nm light improved quality of life and reduced disease severity belotto, 2013* brazil case series (3) pdt 5 ns 5:0 pdt improved inflammation and drainage braunberg er, 2018* usa case series (3) co2 38 37.5 ns co2 laser excision is a safe and effective treatment bu, 2017 china case series (3) pdt 7 24.4 0:7 surgery combined with pdt improved dlqi and vss scores calzavarapinton, 2013 italy case series (3) pdt 6 34 (10.9) 5:1 mal-pdt was effective and well tolerated crocco, 2015 brazil case series (3) co2 3 29.3 2:1 co2 laser effective in hurley iii hs darlymple, 1987 uk case series (3) co2 6 ns 5:1 co2 laser was effective with minimal scarring esposito, 2020 italy case series (3) peht 11 15.7 9:2 peht was effective with low recurrence rates fabbrocini , 2018 italy case series (3) diode laser 20 26.6 (7.84) 14:6 1064nm intralesional diode laser reduced sartorius score and dlqi, increased hiscr fadel, 2015 egypt rct^ (1) pdt 10 27.1 (5.09) 7:4 significant reduction in hslasi with pdt finley, 1996 usa case series (3) co2 7 (20-46) ns co2 laser is effective with low recurrence rates giacaman, 2019* spain case series (3) pdt 8 ns 43:34 adalimumab and pdt decreased lesions and pain gold, 2004 usa case series (3) pdt 4 27.8 (1946) 4:0 ala-pdt is effective in hs patients who did not respond to medical therapy grimstad, 2019 norway case series (2) co2 156 39.3 (9.91) 191:6 7 better response with surgical versus medical treatments. co2 laser was most effective. hazen, 2010* usa case series (3) co2 61 38.5 (2173) 42:19 co2 laser excision and marsupialization is effective for persistent or late-stage hs highton, 2011 uk case series (3) ipl 17 34 (17-50) 14:3 ipl reduced sartorius scores compared to control with good patient satisfaction jain, 2012 india case series (3) co2 nd:yag 4 (30-40) 4:0 deroofing with co2 laser combined with nd:yag was effective with no recurrence lapins, 1994 swede n case series (3) co2 24 36 (22-57) 21:3 co2 laser was effective for patients with chronic hs with low recurrence rates lapins, 2002 swede n case series (3) co2 34 33.9 (11.0/1555) 31:3 scanner-assisted co2 laser ablation improved scarring and had high patient satisfaction madan, 2008 uk case series (3) co2 9 39 (27-52) 8:1 co2 laser was an effective treatment for patients with recalcitrant hs skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 612 mahmoud, 2010 usa rct^ (1) nd:yag 22 41 (19-72) 19:3 nd:yag + topical bpo & clindamycin better than topical bpo & clindamycin alone mikkelsen, 2015 denma rk case series (3) co2 58 37.8 (2154) 48:10 co2 laser treatment effective for recurrent hs naouri, 2020 france rct^ (1) nd:yag 31 ns ns nd:yag laser for hair removal has no effect on disease flares passeron, 2009 france case series (3) pdt 4 ns ns pdl-pdt was not effective in treating hs piccolo, 2014 italy case series (3) ipl 2 32 (26-38) 1:1 ipl completely resolved hs lesions rodriguez -prieto, 2013 spain case series (3) pdt 3 47 (36-62) 0:3 no recurrence after ala-pdt rucker wright, 2009 usa case series (3) nd:yag 20 ns ns nd:yag laser reduced hslasi scores shareef, 2011 uk case series (3) puva 13 35 (25-66) 11:2 puva is an effective treatment in some patients sotiriou, 2009 greece case series (3) pdt 5 33.6 (2543) 2:3 no significant improvement after ala-pdt strauss, 2005 uk case series (3) pdt 4$ ns ns no significant improvement after ala-pdt suarezvalladares , 2018* spain case series (3) pdt 5 ns ns resolution with no recurrence after ala-pdt suarezvalladares , 2017 spain case series (3) pdt 38 36 (30-44) 18:20 complete response in most patients after ala-pdt theut riis, 2018 denma rk case series (3) ipl 25 39.2 (10.9/1763) 25:0 ipl effective as an adjuvant treatment in a subset of patients valladares -narganes , 2015 spain case series (3) pdt 27 30.3 (1962) 11:16 ala-pdt effective in most patients and improved sartorius score vilarrasa, 2019* spain case series (3) pdt 28 46 13:15 ala-pdt improved dlqi and pain vossen, 2018 the netherl ands case series (3) nd:yag 15 34.1 (10.1) 5:10 nd:yag reduced number of flares and reduced disease severity wilden, 2019 germa ny rct (1) ipl + radiofrequ ency 41 38 (23-57) 31:12 ipl and radiofrequency reduced lesion count and dlqi compared to either treatment alone xu, 2011 usa rct^ (1) nd:yag 19 37 (23-54) 16:3 nd:yag improved hs-lasi score zhang, 2016 china case series (3) pdt 3 (17-38) 0:3 ala-pdt ineffective for latestage hs ala: aminolevulinic acid, bpo: benzoyl peroxide, co2: carbon dioxide, dlqi: dermatology life quality index, f: female, hiscr: hidradenitis suppurativa clinical response, hs: hidradenitis suppurativa, hs-lasi: hidradenitis suppurativa lesion, area, and severity index, ipl: intense pulsed light, loe: level of evidence, mal: methyl aminolevulinate, m: male, nd:yag: neodymium-doped yttrium aluminum garnet, ns: not specified, pdl: pulsed dye laser, pdt: photodynamic therapy, peht: pediatric endoscopic hs treatment, puva: psoralen and ultraviolet a, rct: randomized controlled trial * abstract only # number of participants included in analysis $ 2 participants completed the study ^ randomized within-patient controlled trial key to evidence-based support: (1) prospective controlled trial; (2) retrospective study or large case series; (3) small case series or individual case reports skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 613 table 2. summary of treatment outcomes by phototherapy intervention for hs light and laser-based treatment modality (pooled n) % patients with any response (n) % adverse events (n) laser surgery: co2 laser, co2 + nd:yag, peht, intralesional diode laser (431) 80 (344) 25 (105/424) co2 (396) 79 (311) 26 (103/393) co2 + nd:yag (4) 100 (4) nr peht (11) 100 (11) 0 (0/11) intralesional diode laser (20) 90 (18) 10 (2/20) field treatment: nd:yag laser, ipl, diode (101) 71 (84) 18 (24/134) pdt (169) 73 (124) 36 (23/64) puva (13) 69 (9) 15 (2/13) n number of patients with outcomes reported co2: carbon dioxide, ipl: intense pulsed light, nd:yag: neodymium-doped yttrium aluminum garnet, pdl: pulsed dye laser, pdt: photodynamic therapy, peht: pediatric endoscopic hs treatment, puva: psoralen and ultraviolet a skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 614 table 3. results of included studies examining multiple outcome measures on hidradenitis suppurativa author , year n mean age (±sd/ range) intervention outcome measure mean before (±sd) mean after (±sd) delta conclusion abdel azim, 2018 20 29.7 (±5) nd:yag and combined co2/nd:ya g pga co2/nd:yag: 20.6 nd:yag: 20.4 co2/nd:yag: 16.9 nd:yag: 24.1 co2/nd:yag: -3.7 nd:yag: 3.7 co2+nd:yag superior to nd:yag alone. combined treatment had a lower rate of recurrence and higher patient satisfaction. vas patient satisfaction n/a co2/nd:yag: 24; nd:yag: 17 n/a agutbusq uet, 2018 7 28.9 i-pdt vas 4.6 (±1.4) n/a n/a i-pdt is more effective for hs hurley stage ii than stage iii. at 6 months, 5/7 patients had no recurrence. dlqi 9.4 (±3.9) 2.2 (±2.1) -7.2 pga 3 (±2.2) n/a n/a us assessments large transverse diameter reduced diameter in treated lesions n/a andin o navar rete, 2014 5 26 (±5) pdt (5 ala; 635nm light) sartorius 35.4 (±4.98) 18.2 (±8.11) -17.2 pdt improved qol and reduced severity of disease. dlqi 28.8 (±2.68) 7.49 (±2.79) -21.31 vas 3 (±0) 0.8 (±0.45) -2.2 belott o, 2013 5 n/a pdt# inflammation, drainage, erythema, edema n/a reduced drainage and inflammation in 60%; partial reduction in 40%. n/a pdt improves inflammation and drainage braun berge r, 2018 38 37.5 co2 laser healing time in smokers n/a smokers: 6 months non-smokers: 6 months n/a after co2 excision – smoking did not affect healing time but diabetics had a prolonged healing time. 3 patients experienced recurrence at a mean of 6 months post procedure. healing time in diabetics n/a diabetics: 7.3 months non-diabetics: 5.4 months n/a recurrence n/a 3 patients n/a bu, 2017 7 24.4 surgery combined with pdt healing time n/a 29.4 days n/a surgery in combination with pdt improved dlqi. no recurrence. advantage of faster healing and less scaring. recurrence n/a no recurrence n/a dlqi 24.1 (±4.3) 5 months post treatment: 4.9 (± 2.8) -19.2 vss n/a 4.6 (±2.4) n/a calza varapinto n, 2013 6 34 (± 10.9) mal-pdt clinical response n/a no/poor response: 17%; moderate: 50%; marked: 33% n/a 2/6 patients had marked improvement, 3 had moderate improvement, and 1 had no/poor response with malpdt treatment. local reaction n/a absent: 17%; moderate: 83%; marked: 0% n/a cosmesis n/a 33% n/a crocc o, 2015 3 29.3 co2 laser clinical response patient 1: abscesses in axilla patient 2: abscesses in axillary, inframammary and inguinal regions patient 3: abscesses in axilla & groin patient 1: successful treatment patient 2: successful treatment patient 3: successful treatment n/a co2 laser effective in hurley iii hs. darly mple, 1987 6 (2043) co2 laser wound healing n/a 3-7 weeks n/a patients reported limited scarring. all patients were disease free at 9 months to 3 years follow up. all recurrence n/a none n/a skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 615 recurrences were in untreated areas. espos ito, 2020 11 15.7 pediatric endoscopic hidradenitis treatment (peht) postoperative vas 0.7 n/a n/a peht was effective with good patient satisfaction and results. time to restart work/school n/a 1.8 days n/a wound healing time n/a 32.5 days n/a recurrence n/a 2 (18%) patients developed lesions in untreated locations n/a fabbr ocini, 2018 20 26.6 (± 7.84) diode laser 1064nm sartorius 28.6 (±13.0) 19.8 (±12.3) -8.8 laser treatment reduced sartorius score, improved hiscr, and reduced dlqi. pga 10 (50%) mild; 10 (50%) moderate n/a n/a hiscr n/a 6 (30%) not achieved; 14 (70%) achieved n/a clinical response n/a 1 (5%) complete response; 7 (35%) good response; 10 (50%) partial response; 2 (10%) no response n/a fadel, 2015 10 27.1 (±5.09 ) pdt (niosomal methylene blue (nmb) vs. free methylene blue (fmb) as a photosensiti zer to ipl) photos patient 1: lesions in right axilla patient 2: groin lesions in a female patient 3: extensive fibrosis in axilla patient 4: hurley stage 3 patient 1: complete clearance of lesions patient 2: improvement in lower part of lesion patient 3: mild improvement patient 4: moderate improvement n/a photosensitization with nmb was more effective compared to photosensitization with fmb. hs-lasi nmb: 14.9 (±6.6); fmb: 14.0 (±7.2) nmb: 3.6 (±3.4); fmb: 7.9 (±5.6) nmb: -11.3; fmb: -6.1 reduction in percentage of lesions n/a nmb: 77.3 (±18.9); fmb: 44.1 (±28.2) n/a finley , 1996 7 (2046) co2 laser healing time n/a 6.6 weeks (±1.9) n/a co2 laser treatment with healing by second intention was effective for hs. all patients were satisfied with results and reported good cosmesis. recurrence n/a 1 patient 8 months post procedure n/a giaca man, 2019 8 38 (media n) i-pdt lesions n/a decrease in lesions n/a there was a decrease in inflammatory lesions and pain. pain n/a decrease in pain n/a gold, 2004 4 27.8 (1946) ala-pdt and blue light lesions patient 1: lesions in axillae and inguinal area patient 2: lesions in axillae patient 3: lesions in inguinal areas patient 4: lesions in inguinal area patient 1: 75% clearance of lesions patient 2: 75% clearance of lesions patient 3: complete clearance of lesions patient 4: 75% clearance of lesions n/a ala-pdt and blue light phototherapy is an effective treatment for patients who did not respond to medical therapy. skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 616 grims tad, 2019 15 6 39.3 (±9.91 ) co2 laser, co2 laser and topical clindamycin, co2 laser and systemic antibiotic sartorius score co2 laser (n=156): 57; co2 laser and topical clindamycin (n=5): 85; co2 laser and systemic antibiotic (n=1): 123 n/a co2 laser (n =156): -33; co2 laser and topical clindamycin (n=5): -36; co2 laser and systemic antibiotic (n =1): -87 co2 laser was the most effective intervention studied. almost half of patients treated with a combination of surgical and medical treatments had a significant improvement in sartorius score. dlqi co2 laser (n=156): 14; co2 laser and topical clindamycin (n=5): 14; co2 laser and systemic antibiotic (n=1): 13 n/a co2 laser (n =156): -5; co2 laser and topical clindamycin (n=5): -6; co2 laser and systemic antibiotic (n =1): 0 hazen , 2010 61 38.5 (2173) co2 laser excision and marsupializa tion recurrence of disease n/a recurrence in 2 patients. average of 4.1 years without recurrence in treated areas (range of 1-17 years). n/a co2 laser excision & marsupialization effective therapy for persistent or latestage hs (when scarring and sinus tract formation present). comfort/ patient satisfaction n/a treatments well tolerated in all patients. n/a healing time n/a 8.8 weeks n/a hight on, 2011 17 34 (1750) ipl (harmony laser; 2x/week for 4 weeks on one area vs contralateral side not treated served as control) sartorius score n/a 3 months post treatment: -56%. 6 months: -44%. 12 months: 33%. control side 3 months: -10%. 6 months: -10%. 12 months: 3%. significant reduction in hs exam score on treated side (p<0.001). significant difference between treated and control sides (p<0.001). reduction in severity of hs with ipl. mean examination score was improved and maintained at 12 months. improvement was also reported by independent analysis of clinical photographs. patients reported high levels of satisfaction with treatment. treated side had significant reduction in sartorius score maintained at 12 months (p=0.001). patient satisfaction n/a treatment side disease clearance: 1 patient excellent results: 2 patients good results: 10 patients 4 patients: fair results control side: no change: 15 patients slight improvement: 1 patient slight decline: 1 patient n/a jain, 2012 4 (3040) nd:yag and co2 laser recurrence of disease n/a no recurrence n/a deroofing with co2 laser combined with nd:yag laser is effective in treating hs, with no recurrence observed up to 3 years. skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 617 lapin s, 1994 24 36 (2257) co2 laser with healing by secondary intention recurrence of disease n/a recurrence: 2 no recurrence: 22 n/a co2 laser treatment with secondary intention for patients with chronic hs is beneficial, safe, and quick, leaving patients with good cosmetic and functional results. healing time n/a 4 weeks (3-5 weeks) n/a scarring/cosm etic appearance n/a all patients satisfied with scar appearance. n/a patient satisfaction n/a patients found this method favourable, willing to repeat procedure if required. n/a lapin s, 2002 34 (±11.0 /1555) scanner assisted co2 laser ablation recurrence n/a recurrence: 4 no recurrence: 30 n/a co2 laser with scanner is a fast and efficient treatment of hs, with satisfactory cosmetic and functional results. healing time n/a 4 weeks (3-5 weeks) n/a pain in postop period (scale from 03) n/a classified as 3: 4 classified as 2: 15 classified as 1: 9 classified as 0: 6 n/a patient satisfaction n/a condition better than pre surgery: 31 patients hardly changed: 2 patients worse: 1 patient n/a mada n, 2008 9 39 (2752) co2 laser excision (prophylactic oral antibiotics for 2 weeks post-op) recurrence of disease n/a no recurrence: 6 active hs at untreated sites adjacent to treated sites: 2 n/a co2 laser is an effective treatment for patients with recalcitrant hs, with patients reporting high satisfaction scores. patient satisfaction n/a 8.5/10 (range of 7-10) n/a wound healing time n/a 2 weeks (range of 1-4) n/a mahm oud, 2010 22 41 (1972) nd:yag laser (combined with topical benzoyl peroxide wash and clindamycin lotion; benzoyl peroxide and clindamycin alone used as control) modified sartorius score (hs lesion area and severity index) at baseline for all sites combined: 31 (sd: 14.9) all control sites combined: 29 (sd:13.2) at 6 months treated sites: 7.6 (sd: 4.1) mean for all control sites: 19.9 (sd: 10.9) average improvement over all anatomic sites was 72.7% on laser treated side and 22.9% on control side (p< 0.05). nd:yag laser & topical benzoyl peroxide + clindamycin are associated with progressive improvement of hs lesions, and are more effective than topical benzoyl peroxide + clindamycin alone. overall high level of patient satisfaction with treatment. patient satisfaction pain associated with hs n/a pain significantly less: 77% moderately less: 15% pain unchanged: 8% n/a patient satisfaction n/a generally satisfied: 55/58 patients n/a mikke lsen, 2015 58 37.8 (2154) co2 patient satisfaction n/a 94.8% (n=55/58) of patients reported a small (n=11) or great improvement (n=44) n/a co2 laser surgery is an effective treatment for symptomatic hs lesions. patient satisfaction is high despite a moderate number of recurrences. skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 618 recurrence of disease n/a 29.3% (n=17/58) of patients reported recurrence of disease in treated areas n/a naour i, 2020 31 not specifi ed nd:yag laser (4 treatments at 6 week intervals) inflammatory lesion count week 0 untreated: 5.86 (±6.29). treated: 5.89 (±4.68). week 22 untreated: 1.69 (±15.01) treated: -1.25 (±10.77) week 30 untreated: -0.81 (±6.08). treated: -2.56 (±4.22). weeks 0-30 untreated: 6.67. treated: -8.45. the laser had no impact on disease recurrence. the effectiveness of laser hair removal in reducing the amount of inflammation lesions decreases with time. proportion of responders to hidradenitis suppurativa clinical response (hiscr) n/a 1-month post tx treated side: 73.7% control side: 52.6% (p= 0.29). 3-month post tx both treated and control sides: 52.6% no significant difference in number of flares between treated and untreated sites at 1 and 3month followup passe ron, 2009 4 not specifi ed pdl-pdt (ala, only one side of axilla or groin was treated – the other used as control) sartorius score pdl-pdt side: 11.25 control side: 11 at 1 month pdl-pdt side: 8.25. control side: 13 at 3 months pdl-pdt side: 9 control side: 8.67 baseline to month 3 pdl-pdt side: -2.25 control side: 2.33 pdl-pdt not effective in treating hs. vas n/a pain was high during treatment. mean: 8 (6-9) n/a piccol o, 2014 2 32 (2638) ipl (6 sessions) sartorius score 30 (24-36) n/a n/a hs lesions were completely resolved, along with achieving hair removal. recurrence n/a hs pustular papules resolved post treatment n/a rodri guezprieto , 2013 3 47 (3662) pdt (intralesional 5-ala and irradiated with diode laser) recurrence of disease n/a patient 1: no recurrence at 9 months patient 2: no recurrence after 14 months patient 3: resolution of symptoms after 7 months n/a no recurrence post intralesional pdt in all 3 patients. share ef, 2011 13 35 (2566) puva (bath) dlqi 16 (11-26) n/a n/a bath puva is possibly an effective treatment modality for some people with hs. disease clearance n/a clear/near clear: 5 patients; moderate clearance: 4; nominimal: 4 n/a sotiri ou, 2009 5 33.6 (2543) pdt (topical 5ala) sartorius score 18.8 17.2 -1.6 no significant improvement post treatment. vas – disease severity and pain 2.4 2.1 -0.3 dlqi n/a n/a reduction in mean of 6.4% 4 pdt (topical ala) sartorius score 17.8 23.3 5.5 skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 619 strau ss, 2005 not specifi ed vas – disease severity 8.1 7.1 -1 no significant improvement post treatment. worsening symptoms for 2 patients. vas pain 7 5.3 -1.7 suare zvallad ares, 2018 5 not specifi ed pdt (intralesional ala) qualitative descriptions by investigators n/a all patients achieved a complete response in the treated lesion n/a resolution of disease in 3/3 patients. no recurrence noted at follow up. suare zvallad ares, 2017 38 36 (3044) i-pdt (5-ala) response to treatment n/a complete response: 29 patients persistence: 8 patients recurrence: 1 patient n/a a complete response (no lesions or symptoms) rate of 76.3%. i-pdt is a potential effective alternative treatment to hs. dlqi median = 10 (7-17) median = 1 (02.25) -9 hss median = 28.5 (11.75-38.5) median = 0 (045) -28.5 theut riis, 2018 25 39.2 (sd 10.9/1 7-63) ipl patient reported disease activity n/a reduced disease activity: 13/25 patients n/a ipl can be used as an adjuvant treatment for hs in those with mild to moderate disease with minimal scar tissue. hair reduction n/a effect on hair in 17/25 patients n/a vallad aresnarga nes, 2015 27 30.3 (1962) i-pdt (5ala) modified sartorius score 20.67 8.81 -11.86 21/27 patients had either a good or complete response to treatment. intralesional application of pdt allows the light to reach various depths with the lowest amount of energy needed. it may be an effective treatment for hs. response to treatment n/a complete response: 10 (37%) good response: 11 (41%) partial response: 5 (19%) n/a vas pain n/a severe pain (9): 1 moderate (6-9): 4 low (<6): 22 n/a vilarr asa, 2019 28 46 pdt (topical 5-ala) dlqi & eva (pain visual scale) n/a n/a all patients showed improvement in dlqi & eva all patients improved in dlqi and eva scores 8 weeks post last treatment session. ultrasound showed a resolution in the lesions of 13 patients, partial resolution in 12 patients, and poor in 3. ultrasound n/a resolution of lesions: 13 patients partial resolution: 12 patients poor: 3 patients n/a vosse n, 2018 15 34.1 (10.1) nd:yag laser (hair removal on patients with mild hs) number of hs flares/month (questionnaire ) <1 flare: 4 patients 1 flare: 2 patients 2 flares: 1 patient 3 flares: 3 patients >3 flares/continuo us inflammation: 5 patients <1 flare: 8 patients 1 flare: 0 2 flares: 3 patients 3 flares: 3 patients >3 flares/ continuous inflammation: 1 patient decrease in number of monthly flares (p=0.019). laser hair removal can be used to prevent the progression of disease. results include decrease in the number of monthly flares, average hs disease severity was significantly lower post treatment (nrs 6.4 ± 2.8 versus nrs 3.6 ± 3.5). overall treatment satisfaction was rated with a nrs score of 6.7 ± 2.4. 2/3 patients would recommend the treatment. nrs disease severity (0-10) nrs 6.4 (±2.8) nrs 3.6 (±3.5) p= 0.01 -2.8 nrs overall treatment satisfaction (010) n/a nrs 6.7 (±2.4) n/a skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 620 dlqi: dermatology life quality index; hss: hidradenitis severity score; mal: methyl amino; n: number of participants; pdt: photodynamic therapy i-pdt: intralesional photodynamic therapy puva: psoralen plus ultraviolet a; us: ultrasonographic; vas: visual analogue scale; vss: vancouver scar scale; qol: quality of life mcid: minimum clinically important difference nrs 30 – 30% reduction to baseline numerical rating score\ # tetracycline used as a photosensitizer combined with 600nm red light wilde n, 2019 13 38 92357) ipl and radiofrequen cy (rf) active lesions count n/a n/a ipl: 0.8 rf group: -0.4 ipl+rf group: -1.3 whole cohort on crossover to ipl+rf for 24 weeks: -3.6 (p=0.001). ipl + rf is a promising treatment for hs, increasing in effect over time and without severe side effects. dlqi n/a n/a ipl group: -1.3 rf group: -5.1 ipl+ rf group: -6.6 (p=0.025). whole cohort on crossover to ipl+rf for 24 weeks: -5.2 (p=0.003). wollin a, 2004 17 (2941) transdermal co2 clinical response n/a n/a improvement of granulation and reduction of discharge and malodor 1-week post treatment xu, 2011 19 37 (2354) 1064nm nd:yag laser lesion area and severity index (lasi) n/a n/a all sites: -31.6% (p<0.05) axillary sites: -24.4% (p=0.08) inguinal site: -36.8% (p=0.001). the percentage change in modified hs-lasi score after 2 months was –31.6% (p<.001) averaged over all anatomic sites. hs-lasi scores trended down from baseline to 1 month and 2 months after treatment for both axilla and inguinal sites. zhang , 2016 3 (1738) pdt (ala) dlqi 26.67 (1.15) session 1: 24.67 session 2: 24.33 session 3: 24.33 n/a no improvement for late-stage hs. fall clinical 2021 leonardi, c, md1; fahrbach, k, phd2; neupane, b, phd2; armstrong, a, md, mph3; gordon, k, md4; kiri, s, msc5; taieb, v, msc5; mcclung, l, phd6 1central dermatology and saint louis university school of medicine, st louis, mo, usa; 2evidera, waltham, ma, usa; 3keck school of medicine usc, los angeles, ca, usa; 4medical college of wisconsin, milwaukee, wi, usa; 5ucb pharma, slough, uk; 6ucb pharma, smyrna, ga, usa number needed to treat among therapies for patients with moderate to severe plaque psoriasis: clinical perspective of results from a network meta-analysis funding provided by ucb pharma introduction objective methods conclusions results (cont’d)methods (cont’d) ⚫ psoriasis (pso) is a chronic, inflammatory, multi-system disease; patients with moderate to severe plaque pso are currently being treated with oral systemic drugs and targeted biologic therapies.1,2 ⚫ while the number of therapies available for the treatment of plaque pso has increased over the last 5–10 years, data from head-to-head comparisons are scant.3 — to address this limitation, we conducted a network meta-analysis (nma), which facilitates the comparison of multiple treatments by simultaneously analyzing the direct evidence of treatments and indirect comparisons of treatments sharing a common comparator.4 ⚫ the number needed to treat (nnt) is a simple, clinically interpretable measure of assessing treatment benefit.5 — it represents the number of patients who would need to be treated with the possible treatment options to demonstrate one additional response over established treatments or placebo. — an nntof one is ideal, indicating that only one patient needs to be treated to receive an additional benefit. as the nnt increases, the less effective the intervention will be. ⚫ a 90% and 100% improvement from baseline in psoriasis area and severity index (pasi 90 or pasi 100) are increasingly recognized as achievable clinical responses.6 ⚫ eighty-six rcts (including 34,129 patients) were included in the nma (figure 1), of which 68 were placebo-controlled trials (26 trials had ≥ three arms including a placebo and an active comparator arm). results references ⚫ the objective of this analysis was to determine the nnt to achieve a pasi 90 or pasi 100 response in the short-term (10 to 16 weeks) for bimekizumab and other approved biologics for the treatment of moderate to severe pso. 1. menter a, strober be, kaplan dh, et al. joint aad-npf guidelines of care for the management and treatment of psoriasis with biologics. j am acad dermatol. 2019;80(4):10291072; 2. menter a, gelfand jm, connor c, et al. joint american academy of dermatology-national psoriasis foundation guidelines of care for the management of psoriasis with systemic nonbiologic therapies. j am acad dermatol. 2020;82(6):1445-1486; 3. wright e, yasmeen n, malottki k, et al. assessing the quality and coherence of network metaanalyses of biologics in plaque psoriasis: what does all this evidence synthesis tell us? dermatol ther (heidelb). 2021;11(1):181-220; 4. dias s, sutton aj, ades ae, welton nj. evidence synthesis for decision making 2: a generalized linear modeling framework for pairwise and network meta-analysis of randomized controlled trials. med decis making. 2013;33(5):607-627; 5. laupacis a, sackett dl, roberts rs. an assessment of clinically useful measures of the consequences of treatment. n engl j med. 1988;318(26):1728-1733; 6. torres t, puig l. treatment goals for psoriasis: should pasi 90 become the standard of care? actas dermosifiliogr. 2015;106(3):155-157; 7. armstrong a, reich k, warren rb, et al. pbi3 comparative efficacy of bimekizumab for the treatment of moderate to severe plaque psoriasis: a network meta-analysis. value in health. 2021;24:s14; 8. papp ka, merola jf, gottlieb ab, et al. dual neutralization of both interleukin 17a and interleukin 17f with bimekizumab in patients with psoriasis: results from be able 1, a 12-week randomized, double-blinded, placebo-controlled phase 2b trial. j am acad dermatol. 2018;79(2):277-286 e210; 9. reich k, papp ka, blauvelt a, et al. bimekizumab versus ustekinumab for the treatment of moderate to severe plaque psoriasis (be vivid): efficacy and safety from a 52-week, multicentre, double-blind, active comparator and placebo controlled phase 3 trial. lancet. 2021;397(10273):487-498; 10. gordon kb, foley p, krueger jg, et al. bimekizumab efficacy and safety in moderate to severe plaque psoriasis (be ready): a multicentre, double-blind, placebo-controlled, randomised withdrawal phase 3 trial. lancet. 2021;397(10273):475-486; 11. warren rb, blauvelt a, bagel j, et al. bimekizumab versus adalimumab in plaque psoriasis. n engl j med. 2021;385(2):130-141; 12. reich k, warren rb, lebwohl m, et al. bimekizumab versus secukinumab in plaque psoriasis. n engl j med. 2021;385(2):142-152. we acknowledge marissa betts, paulina kazmierska, and mahmoud slim for their contributions to the slr and nma updates. acknowledgments figure 1. network diagram for trials reporting pasi outcomes (n=86) presented at the fall clinical dermatology conference (fc21) • october 21–24, 2021 • las vegas, nv, usa table 1. inclusion/exclusion criteria for nma picos inclusion for analysis exclusion criteria population adult (≥18 years) patients with moderate to severe chronic plaque pso with or without comorbid psa studies providing subgroup data for those with moderate to severe plaque pso studies in patients primarily in psa or with a treatment focus for psa intervention/ comparator protocol approved doses of systemic biologic therapies (adalimumab, bimekizumab, brodalumab, certolizumab pegol, etanercept, guselkumab, infliximab, ixekizumab, risankizumab, secukinumab, tildrakizumab, ustekinumab) systemic non-biologics (acitretin, apremilast, cyclosporine, dimethyl fumarate, methotrexate) studies in biosimilar compounds outcomes any combination of pasi 50, 75, 90 and/or 100 presented as discrete/categorical outcomes mean change in pasi score study design treatment induction period in randomized controlled trials observational/rwe studies single-arm trials ole follow-up periods that are not randomized timepoints 10 to 16 weeks <10 weeks or >16 weeks abbreviations: ole = open-label extension; pasi = psoriasis area and severity index; picos = population, intervention, comparison, outcomes, and study design; psa = psoriatic arthritis; pso = psoriasis; rwe = real-world evidence ⚫ the nnts of biologic treatments compared to placebo to achieve one additional pasi 90 or pasi 100 response were calculated as the reciprocal of the corresponding absolute risk differences obtained from the nma. — the median and (2.5th and 97.5th) percentiles of the posterior samples, obtained from the bayesian nma, were used as estimates of the relative risks to achieve pasi 90 or 100 compared to placebo and their 95% credible interval (cri). figure 2. number needed to treat (95% cris) for biologic treatments vs. placebo for achieving pasi 90 ⚫ trial populations were generally similar with respect to age and sex. participants in the different treatment arms were, on average, between 38.3 to 55.3 years old, and were mostly of male sex. ⚫ patients had moderate to severe pso for an average duration of 11 to 24 years and the prevalence of comorbid psoriatic arthritis ranged between 2.4% and 36.8%. ⚫ the re, rez model showed that interleukin inhibitors—including bimekizumab 320 mg, risankizumab 150 mg, ixekizumab 80 mg, brodalumab 210 mg, guselkumab 100 mg, and secukinumab 300 mg—were the most effective treatments in the network across all pasi response levels. ⚫ bimekizumab had the lowest positive nnt (closest to one) to achieve pasi 90 and pasi 100, followed by risankizumab 150 mg, ixekizumab 80 mg, and brodalumab 210 mg (figure 2 and figure 3). — the nnt of bimekizumab versus placebo to achieve pasi 90 was 1.22, which means that for every 122 patients treated with bimekizumab or placebo, 100 more patients will achieve pasi 90 in the bimekizumab group compared to placebo. — the nnt versus placebo was 1.40 for risankizumab 150 mg, 1.45 for ixekizumab 80 mg, 1.42 for brodalumab 210 mg, 1.52 for guselkumab 100 mg, 1.62 for secukinumab 300 mg, 2.30 for ustekinumab 45 or 90 mg, 2.29 for adalimumab 40 mg, 2.80 for tildrakizumab 100 mg, and 4.61 for etanercept 50 mg. — the nnts to achieve pasi 100 were: 1.74 for bimekizumab 320 mg, 2.30 for brodalumab 210 mg, 2.26 for risankizumab 150 mg, 2.65 for ixekizumab 80 mg, 3.11 for secukinumab 300 mg, 3.08 for guselkumab 100 mg, 5.72 for ustekinumab 45 or 90 mg, 5.78 for adalimumab 40 mg, 7.61 for tildrakizumab 100 mg, and 16.77 for etanercept 50 mg. bimekizumab 320 mg risankizumab 150 mg brodalumab 210 mg ixekizumab 80 mg guselkumab 100 mg secukinumab 300 mg infliximab 5 mg/kg certolizumab pegol 400 mg adalimumab 40 mg ustekinumab 45 or 90 mg ustekinumab 90 mg certolizumab pegol 200 mg secukinumab 150 mg tildrakizumab 200 mg tildrakizumab 100 mg etanercept 50 mg etanercept 25 mg 1 2 3 4 5 6 7 8 9 > bimekizumab 320 mg risankizumab 150 mg brodalumab 210 mg ixekizumab 80 mg guselkumab 100 mg secukinumab 300 mg infliximab 5 mg/kg ustekinumab 45 or 90 mg adalimumab 40 mg certolizumab pegol 400 mg ustekinumab 90 mg tildrakizumab 200 mg certolizumab pegol 200 mg secukinumab 150 mg tildrakizumab 100 mg etanercept 50 mg etanercept 25 mg 1 6 11 16 21 26 31 36 > abbreviations: cri = credible interval; nnt = number needed to treat; pasi 90 =90% improvement from baseline in psoriasis area and severity index; vs = versus abbreviations: cri = credible interval; nnt = number needed to treat; pasi 100 = 100% improvement from baseline in psoriasis area and severity index; vs = versus figure 3. number needed to treat (95% cris) for biologic treatments vs. placebo for achieving pasi 100 ⚫ fewer patients are required to be treated with bimekizumab to have one additional responder of pasi 90 and pasi 100 compared to all other agents in moderate to severe pso. ⚫ interleukin inhibitors were highly effective in short-term improvement of pso symptoms, requiring fewer patients to achieve an additional pasi response among patients with moderate to severe disease. disclosures cl speaker (honoraria) for abbvie, celgene, eli lilly and novartis; served as an investigator for actavis, abbvie, amgen, boehringer ingelheim, celgene, coherus, corrona, dermira, eli lilly, galderma, glenmark, janssen, leo pharma, merck (msd), novartis, novella, pfizer, sandoz, stiefel and wyeth; consulting and advisory board honoraria for abbvie, amgen, boehringer ingelheim, dermira, eli lilly, janssen, leo pharma, pfizer, sandoz, ucb pharma and vitae; kf, nb are employees of evidera inc.; aa data safety monitoring board member for boehringer ingelheim/parexel; received research funding from bms, dermavent, dermira, eli lilly, galderma, janssen, kyowa hakko kirin, leo pharma, pfizer, ucb pharma; research investigator without compensation for sanofi genzyme; scientific investigator for abbvie, bms, dermavent, eli lilly, janssen, leo pharma, modernizing medicine, novartis, ortho dermatologics, pfizer, regeneron, sanofi genzyme, sun pharma; speaker for abbvie, regeneron, sanofi genzyme; kg consulting fees from abbvie, almirall, amgen, boehringer ingelheim, bms, celgene, dermira, eli lilly, janssen, novartis, pfizer, sun pharma and ucb pharma; research support from abbvie, bms, celgene, eli lilly, janssen, novartis and ucb pharma; sk, vt, lm are employees of ucb pharma. ⚫ we conducted a systematic literature review (slr) in july 2020 to identify randomized controlled trials (rcts) assessing the efficacy and safety of biologic and non-biologic therapies in the management of moderate to severe pso.7 ⚫ studies were included if they assessed the response to biologic therapies (at dosages approved by the food and drug administration as well as some doses approved by the european medicines agency) and non-biologic therapies via the percentage improvement in pasi scores from baseline at 10 to 16 weeks (table 1). — ten to 16 weeks encompasses the range of stated primary endpoint timepoints across studies, and we have selected response data at the stated primary endpoint. ⚫ data from five bimekizumab trials (published phase 2b [be able 18], and phase 3/3b [be vivid, be ready, be sure, and be radiant]9-12) in pso were included. ⚫ a bayesian multinomial likelihood nma model (probit link) was conducted to compare the relative effects in achieving each of the pasi categories (i.e., 50%, 75%, 90% and 100% improvement) across treatments. two modifications were implemented in this model: — the models were adjusted for the baseline risk, i.e., controlling for the relationship between placebo rate and relative effects versus placebo. — the multinomial assumption of the standard model was relaxed by allowing treatments to have different efficacies across the different pasi levels. this novel modification added a random-effects (re) component to parameter z, which reflects the difficulty to achieve the next highest pasi level, and is referred to as the ‘rez’ model. ⚫ non-biologic treatments were included in the nma. however, only the results of biologic treatments are presented due to their increased relevance in the evolving treatment landscape in the management of moderate to severe pso and to ensure clarity of presentation. abbreviations: il = interleukin; pasi = psoriasis area and severity index; tnf = tumor necrosis factor nnt nnt nnt (95% cri) 1.22 (1.16,1.29) 1.40 (1.32,1.50) 1.42 (1.32,1.53) 1.45 (1.35,1.58) 1.52 (1.42,1.67) 1.62 (1.50,1.77) 1.91 (1.71,2.15) 2.14 (1.85,2.53) 2.29 (2.08,2.55) 2.30 (2.10,2.56) 2.49 (1.97,3.30) 2.50 (2.12,3.04) 2.54 (2.13,3.01) 2.63 (2.20,3.22) 2.80 (2.33,3.47) 4.61 (4.03,5.35) 8.26 (6.13,11.69) previously presented at amcp nexus 2021 nnt (95% cri) 1.74 (1.58,1.96) 2.26 (2.01,2.59) 2.30 (2.02,2.65) 2.65 (2.28,3.13) 3.08 (2.63,3.67) 3.11 (2.69,3.63) 4.27 (3.10,6.33) 5.72 (4.88,6.79) 5.78 (4.90,6.92) 5.98 (4.36,8.63) 6.48 (3.94,11.80) 6.96 (5.09,9.78) 7.19 (5.12,10.60) 7.24 (5.34,9.72) 7.61 (5.55,10.80) 16.77 (13.10,22.11) 37.62 (19.18,87.24) skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 1 in-depth review a review of the evidence for intrinsic ethnic differences as important determinants of skin aging and carcinogenesis: a hope for all ethnicities stephanie chan, bs1, jodie sasaki, md2, abrar qureshi, md, mph1, grace giordano3, john koo, md4, nicholas brownstone, md5 1 department of dermatology, brown warren alpert medical school, providence, rhode island 2 department of dermatology, university of washington valley medical center, seattle, washington 3 barnard college, new york, ny 4 department of dermatology, university of california san francisco, san francisco, california 5 national society for cutaneous medicine, new york, ny aging is an important and current topic in dermatology. by the year 2030, over 20% of u.s. residents are projected to be 65 years or older, compared with 13% in 2010.[1] skin aging encompasses an entire spectrum of changes starting with fine rhytids, discolorations, and benign keratosis, progressing to deeper rhytids, precancerous lesions, and eventually skin cancers. ethnic differences in the aging process, including age of onset and severity of skin aging have been described. defining the structural, functional, and biochemical differences in the skin of individuals from different ethnic backgrounds has been of interest in many fields including dermatology. studies of pigmentary differences (size, distribution of melanosomes) have yielded the most consistent results, however studies regarding differences in other skin components have yielded inconclusive results.[2] skin pigmentation, or lack there of it, is thought to be the main determinant of how quickly (or slowly) people age. many people, including dermatologists have traditionally assumed that the most important driver of abstract by the year 2030, an estimated 1 in every 5 us residents will be over 65 years of age. skin aging, which encompasses an entire spectrum of changes starting with fine rhytids (wrinkles), discolorations, and benign keratoses, progressing to deeper wrinkles, pre-cancerous lesions, and eventually skin cancers is of particular interest in dermatology. skin pigmentation, or lack of it, is thought to be the most important determinant of how quickly (or slowly) people age. however, there is data suggesting that this may not be the case and other factors, such as ethnic differences in dna repair may also play a major role. this article reviews available data on the differential aging process by ethnic background. the findings strongly suggest that there are other important determinants of aging besides skin color where future research may suggest ways to slow or reverse skin aging which can possibly benefit all ethnicities. introduction skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 2 skin aging is fitzpatrick skin type (fst) and/or skin color. however, more recent data suggests that other factors such as ethnic differences in dna repair may also play a key role in aging. although darker skin types are less prone to the damaging effects of uv exposure, other factors may also influence the progression of skin aging. here we present data suggesting that population differences in other genetic factors, such as ethnic differences in dna repair and gene polymorphisms may be just as important as pigmentation in determining the propensity and pace of skin aging. studies were identified by searching pubmed and medline databases. search terms included “skin carcinogenesis”, “skin aging”, “ethnicity”, “dna repair.” we only included published articles in peer-reviewed journals that were written or translated in english. no year limits were applied and therefore included the full year range of the database until november 2020. ethnic differences in skin aging and carcinogenesis it is well known that various ethnicities age differently. more specifically, several publications present data which suggest that the aging process in asians begins significantly later than in caucasians. in a cross-sectional study comparing the age of occurrence and severity of signs of skin aging of 256 women in sendai, japan and 280 women in paris, france, rhytids occurred at comparable severity and frequency on average 15 years earlier in french women below 65 years old.[3] more specifically, rhytids, including expression lines on the forehead, frown lines, crow’s feet, rhytids under the eyes and rhytids on upper lip were more pronounced at an earlier age in french women than in japanese women. however, after 65 years of age the differences between the 2 populations are no longer significant. comparing chinese women again to french women a 10-year delay in rhytid onset in chinese women was documented, supporting the ethnic population-related difference in the kinetics of rhytid severity.[4] rhytid severity in french women followed a linear increase during aging while rhytid severity in chinese women appeared to go through two stages—a slow increase until the age of 50 followed by a faster increase thereafter. in fact, after 60 years of age, the severity of rhytids was similar between both the chinese and french population—in the same way that japanese women matched their french counterparts after 65 years of age. lastly, another study documented a similar result comparing wrinkle formation and skin sagging between caucasians in america and japanese in japan.[5] as demonstrated in the above two studies, they also found that japanese wrinkle scores were significantly lower than caucasians in all areas of the face in younger age groups (20-49). however, wrinkle scores are similar by the age 50-60 years of age. moreover, with regard to the most severe end of the skin-aging spectrum, skin cancer formation; there is also a large difference in risk of cancer by ethnicity. in a “head to head” comparison of nonmelanoma skin cancer among dermatology patients in osaka university medical center as compared to patients from colorado university, patients in japan had 1/100 of the risk of patients in the united states.[6] the rate of skin cancers in caucasians compared to east asians and pacific islanders (japanese, methods results skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 3 chinese, korean, hawaiian, filipino) living in hawaii was 45:1.[7] individual topology angle (ita) individual topology angle (ita) was developed as an objective classification of skin color based on colorimetric parameters l* (luminance) and b* (yellow/blue component). although individuals with red hair and blue eyes have clearly lighter skin than asian individuals, when a large population is studied, on average, according to the most rigorous objective quantification, there is significant overlap between caucasian, russian, chinese and japanese women (figure 1).[8] fitzpatrick skin phototype or color not necessarily a predictor of skin aging there are available data to suggest that the above difference in skin aging by ethnicity is not simply determined by the pigmentation of the skin; in fact, skin coloration may not even be the most important factor on skin aging. here are the data documenting that, within non-caucasian ethnic groups, some ethnicities with darker skin ages faster than lighter skin groups. hillebrand et al. conducted a large population survey involving more than 2000 subjects in los angeles, rome, london, akita and kagoshima (japan). surprisingly, with regard to signs of aging such as facial wrinkling, asians showed the least amount of wrinkling, even as compared to african americans.[9] as expected, caucasians showed more wrinkling than either asians or african americans. latinos showed wrinkling figure 1. individual typology angle (ita) values of caucasian, russian, chinese and japanese woman (adapted from del bino s, bernerd f. variations in skin color and the biological consequences of ultraviolet radiation exposure. br j dermatol. 2013;169 suppl 3:33–40. [pmid: 24098899].) similar to african americans, even though latinos and asians were similar in coloration as measured by the investigators. interestingly, in this study, east asians living in los angeles (japanese, korean, chinese) showed no significant difference in facial wrinkling compared to women living in japan. in another study, women in bangkok, thailand showed more severe level of wrinkling compared to japanese or chinese women despite the fact that thai women were documented to be naturally more darkly pigmented than japanese or chinese women.[5,8] skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 4 the reviewed evidence suggests that there are other intrinsic factors that may play a critical role in determining the aging process in addition to skin pigmentation. as documented above, there is data showing that certain ethnic groups with lighter skin, such as east asians develop signs of aging such as facial wrinkling much later than african americans. the data comparing the skin aging signs of thai women when measured against japanese and chinese women also indicate that darker pigmentation does not always lead to less or slower skin aging. moreover, the tremendous difference in skin cancer risk between caucasian and japanese as documented in “head-to-head” comparison between university of colorado and university of osaka cannot be fully explained by the difference in skin pigmentation when the skin pigmentation appears similar between these two groups when rigorously measured (ita). it is traditionally believed that increased amounts of melanin better protect against uv-induced dna damaged which then leads to decreased skin aging and carcinogenesis.[10] sheehan et. al. documented that uv-induced dna damage occurred to the similar extent in individuals with fst ii and fst iv skin; however, individuals with fst iv skin repair the experimentally induced damage more rapidly compared to those with fst ii skin.[11] what explains these notable differences between various ethnic groups regarding how their skin ages ranging from wrinkles to skin cancers? there are several possible explanations that underlie these differences. for one, sheenhan et. al. have documented difference in dna repair capacity in skin by different fst. more specifically, after multiple exposures, the uv-induced dna damage was repaired more rapidly among individuals with fst iv skin compared to fst ii. the authors hypothesized that the more rapid repair may be due to a uvinducible sos-like response previously described by several authors.[12] there is also the possibility of genetically determined differences among ethnic groups in the robustness of the dna repair mechanisms. certain variants for melanocortin receptor (mc1r) are associated with an increased risk of nmsc independent of skin color, hair color, and self-reported phenotypic pigmentation.[13] therefore, the differences in ethnic aging may be also be due to certain existence of the variants for mc1r. ethnic difference in telomere length and dna repair capacity represents another possible area of research in anti-aging. in addition to the possible variation in dna repair, it is well accepted that telomere shortening and damage is associated with the aging process. there is increasing evidence that telomerase, the enzyme that preserves the length of telomeres, may play a critical role in aging of the skin. the available data suggests that there are polymorphisms of telomerase[14]. therefore, it is entirely possible that different ethnic groups (for example, caucasians versus east asians/africans), may in fact have telomerase of varying efficacy that may explain the phenotypic differences in skin cancer risk and aging as documented above. few preliminary studies have investigated telomere length and aging. brown et. al. demonstrated that even though telomere length may differ amongst gender or race, it does not account for differences in discussion skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 5 population health outcomes[16]. furthermore, a study on salivary telomere table 1. non-topical agents that enhance dna repair non-topical agent mechanism of action clinical applications polypodium leucotomos extract • decreases lipid peroxides and neutralizes superoxide anions and free radicals • anti-inflammatory properties – reduction of uvinduced cyclooxygenase-2, p53 suppressor genes, and formation of cyclobutene pyrimidine dimers (cpd) • prevention of polymorphous light eruption and photodermatoses[15] • decreases acute pigment darkening[16] nicotinamide • cofactor of atp and enhances dna repair • treatment and prevention of nonmelanoma skin cancers and actinic keratosis[17] table 2. topical agents that enhance dna repair topical agents mechanism of action dna repair enzymes photolyase • dna repair enzyme splits cyclobutene; therefore reducing cyclobutene pyrimidine dimers (cpd) present[18] • shown to decrease actinic keratoses (ak)[19] topical t4 endonuclease v • dna repair enzyme derived from the uv-resistant microbe micrococcus luteus • enhances dna repair by removing cyclobutene pyrimidine dimers (cpds)[20] green tea polyphenols • green tea has green tea polyphenols such as epigallocatechin-3-gallate (egcg) • induce dna repair via induction of il-12 keratinocytes • protects epidermal langerhans cells from uv damage and uv-induced damage[21,22] nicotinamide (vitamin b3) • essential coenzyme for cellular atp production and dna repair • decreased nicotinamide slows dna repair[23,24] skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 6 length did not account for race/ethnic differences in late life health and is not significantly associated with indicators of health among different races. these studies did not investigate telomere repair capacity specifically[17]. therefore, the authors recommend future research to be focused on the ethnic differences in telomere and dna repair capacity given the paucity of studies in this area. a review of the literature regarding skin aging and carcinogenesis revealed a significant difference among ethnic groups. interestingly, the degree of skin pigmentation, even though important appears not entirely adequate to explain the documented differences in aging and the risk of carcinogenesis. a recent review on the lack of correlation between uv exposure and melanoma risk in skin of color also suggests that something other than uv exposure and skin pigmentation may be a more important determinant.[15]. a more advanced and accurate understanding of the skin aging process that goes beyond pigmentary differences may uncover new ways to minimize skin aging. enhancing dna repair through topical and oral treatments is already a reality through several of the following treatments. oral agents such as polypodium leucotomos extract (ple)[18] and nicotinamide (vitamin b3) and topical agents such as dna repair enzymes and green tea polyphenols are all supplements that can enhance dna repair (table 1 and 2). these treatments may offer more hope to counter skin aging beyond skin pigmentation. further research regarding differences in dna repair mechanisms extends beyond the field of dermatology and examines how dna repair mechanisms may affect neurological disorders. recent research notes that patients with neurodegenerative disorders like huntington’s disease and alzheimer’s disease share an endophenotype of impaired dna damage repair[19].with the recent identification of this endophenotype researchers are now able to explore new opportunities in therapeutic interventions[20]. this demonstrates that this research and its potential therapeutic benefits are already being investigated for use in other disease states outside of cutaneous pathophysiology. the differential aging process by ethnic background as well as basic science progress on skin aging was reviewed in this article. the data reviewed here indicates that skin aging is multifactorial in origin. while differences in skin aging and skin repair were highlighted here amongst different races, it is important to remember that we are all human beings. as such, the authors hope that the information presented here will educate readers and encourage future investigations on this topic with the goal of making use of the documented differential speed of aging between different ethnic groups as a “door of opportunity” that can lead us to find novel ways to mitigate skin aging and skin carcinogenesis to improve patient care and quality of life for people of all ethnicities. conflict of interest disclosures: none funding: none corresponding author: stephanie chan, bs 515 spruce street san francisco, ca 94118 858-776-1552 email: stephanie_chan@brown.edu references: conclusion skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 7 1. office ucbpi. 2010 census shows 65 and older population growing faster than total u.s. population 2010 census newsroom u.s. census bureau. n.d. https://www.census.gov/newsroom/releases/archi ves/2010_census/cb11-cn192.html (accessed 13 november 2020). 2. del bino s, duval c, bernerd f. clinical and biological characterization of skin pigmentation diversity and its consequences on uv impact. int j mol sci. 2018;19. [pmid: 30205563]. 3. tschachler e, morizot f. ethnic differences in skin aging. in: skin aging. gilchrest ba, krutmann j, editors. springer; 2006. p. 23–31. 4. nouveau-richard s, yang z, mac-mary s, et al. skin ageing: a comparison between chinese and european populations. a pilot study. j dermatol sci. 2005;40:187–93. [pmid: 16154324]. 5. tsukahara k, fujimura t, yoshida y, et al. comparison of age-related changes in wrinkling and sagging of the skin in caucasian females and in japanese females. j cosmet sci. 2004;55:351–71. [pmid: 15386027]. 6. tada m, miki y. malignant skin tumors among dermatology patients in university hospitals of japan. the journal of dermatology. 1984;11:313–21. [doi: https://doi.org/10.1111/j.13468138.1984.tb01484.x]. 7. allison sd, wong kl. skin cancer: some ethnic differences. ama arch derm. 1957;76:737–9. [doi: 10.1001/archderm.1957.01550240055011]. 8. del bino s, bernerd f. variations in skin colour and the biological consequences of ultraviolet radiation exposure. br j dermatol. 2013;169 suppl 3:33–40. [pmid: 24098899]. 9. hillebrand g. the age-dependent changes in skin condition in african americans, caucasians, east asians, indian asians and latinos. ifscc magazine. 2001;4:259–66. 10. brenner m, hearing vj. the protective role of melanin against uv damage in human skin. photochem photobiol. 2008;84:539–49. [pmid: 18435612]. 11. sheehan jm, cragg n, chadwick ca, potten cs, young ar. repeated ultraviolet exposure affords the same protection against dna photodamage and erythema in human skin types ii and iv but is associated with faster dna repair in skin type iv. j invest dermatol. 2002;118:825–9. [pmid: 11982760]. 12. gilchrest ba, eller ms, yaar m. telomeremediated effects on melanogenesis and skin aging. j investig dermatol symp proc. 2009;14:25–31. [pmid: 19675549]. 13. han j, kraft p, colditz ga, wong j, hunter dj. melanocortin 1 receptor variants and skin cancer risk. int j cancer. 2006;119:1976–84. [pmid: 16721784]. 14. koziel je, fox mj, steding ce, sprouse aa, herbert b-s. medical genetics and epigenetics of telomerase. j cell mol med. 2011;15:457–67. [pmid: 21323862]. 15. lopes fcps, sleiman mg, sebastian k, et al. uv exposure and the risk of cutaneous melanoma in skin of color: a systematic review. jama dermatology. 2021;157:213–9. [doi: 10.1001/jamadermatol.2020.4616]. 16. brown l, needham b, ailshire j. telomere length among older u.s. adults: differences by race/ethnicity, gender, and age. j aging health. 2017;29:1350–66. [pmid: 27469599]. 17. brown l, garcía c, ailshire j. does salivary telomere length explain race/ethnic differences in aging? biodemography soc biol. 2019;65:351–69. [pmid: 33335644]. 18. nestor ms, berman b, swenson n. safety and efficacy of oral polypodium leucotomos extract in healthy adult subjects. j clin aesthet dermatol. 2015;8:19–23. [pmid: 25741399]. 19. shiwaku h, okazawa h. impaired dna damage repair as a common feature of neurodegenerative diseases and psychiatric disorders. curr mol med. 2015;15:119–28. [pmid: 25732151]. 20. maiuri t, suart ce, hung clk, et al. dna damage repair in huntington’s disease and other neurodegenerative diseases. neurotherapeutics. 2019;16:948–56. [pmid: 31364066]. skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 512 original research non-invasive detection of genomic atypia increases real-world npv and ppv of the melanoma diagnostic pathway and reduces biopsy burden maral k. skelsey, md1, brook brouha, md, phd2, jim rock, ms3, michael d. howell, phd3 burkhard jansen, md3, loren e. clarke, md3, gary peck, md 4 1 department of dermatology, georgetown university school of medicine, washington, dc 2 west dermatology, la jolla, ca 3 dermtech, inc. la jolla, ca 4 dermatologic surgery center of dc, chevy chase, md cutaneous melanoma is responsible for more than 7,000 deaths in the united states each year1. accurate detection of melanoma in its earliest stages is critical to optimizing patient outcomes, since 5-year survival of 9899% for early-stage melanoma can be achieved with wide local excision.1 however, melanoma detection relies primarily on abstract background: management of pigmented lesions currently relies on visual assessment with surgical biopsy and histopathologic examination for those lesions suspicious for melanoma. a non-invasive genomic assay that detects two melanoma-associated biomarkers (pla, 2-gep) has recently been validated as an adjunct to visual assessment for distinguishing high-risk pigmented lesions appropriate for biopsy from those that can be safely monitored via clinical surveillance. methods: real-world npv was determined by following a cohort of 1,233 pla-negative pigmented lesions for evidence of malignancy for up to 36 months and by re-testing a separate prospective cohort of 302 pla-negative lesions up to 2 years after initial testing. real-world ppv was determined by identifying melanoma diagnoses among pla-positive lesions within a us-based registry of 3,418 platested cases. results: ten early-stage melanomas (4 in situ and 6 pt1a) were identified among 1,233 pla-negative lesions (0.8%), corresponding to a real-world npv of 99.2% (ci 95% = 98.5 99.6). of 302 initially planegative lesions subjected to repeat testing an average of 15 months later, 34 were pla-positive. biopsy revealed 3 melanomas (all in situ), further confirming an npv of > 99%. among 316 pla-positive cases, 59 were diagnosed as melanoma by histopathology, corresponding to a ppv of 18.7%. of all pla-positive lesions, 30.5% had histopathologic diagnoses corresponding to high-risk mpath-dx categories (classes iii-v). conclusions: the pla has an npv of >99% within the real-world intended use population. the pla has a ppv of 18.7% for melanoma and also detects high-risk lesions such as dysplastic nevi with severe / high-grade atypia that are generally targeted for complete excision. introduction skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 513 subjective visual assessment of pigmented lesions clinically suspicious of melanoma. clinicians use e.g. abcde criteria or ‘ugly duckling’ signs to identify those lesions that need additional evaluation by biopsy where malignancy is confirmed by histopathologic evaluation within only a small proportion of specimens. in a study by anderson involving 4,039 pigmented lesions selected for biopsy based on visual criteria, just 149 (3.7% or 1 in 27) were confirmed as melanoma.2 dermoscopy and other in vivo diagnostic aids have been shown to reduce biopsies of benign neoplasms when applied by skilled users, but many pigmented lesions are evaluated by providers who lack dermoscopy expertise. few, if any studies exist in which melanocytic lesions considered benign by visual assessment undergo biopsy to determine the proportion of true negatives, and thus the real-world negative predictive value (npv) of visual assessment is difficult to establish. most investigations estimate npv by comparing histopathologic diagnoses of biopsied lesions to clinical images. a study by nachbar and colleagues evaluated 172 lesions and calculated an npv of 73% for unaided clinical assessment and 85% for clinical assessment with dermoscopy.3 regardless of the precision of such estimates, there is a need for technologies and approaches that effectively differentiate pigmented lesions that need further evaluation by biopsy from those that can be safely managed with clinical surveillance. differentiation of melanomas from the benign nevi that may simulate them may also present challenges at the histopathologic level. early-stage lesions in particular generate considerable uncertainty and diagnostic disagreement among pathologists.4,5 in an effort to improve pathologist concordance, the recentlyintroduced mpath-dx classification scheme categorizes melanocytic lesions by recommended treatment rather than specific diagnosis. based on histopathologic features and perceived risk of progression, pathologists assign lesions to one of five classes, each with a corresponding treatment recommendation.6 melanomas and high-risk lesions constitute classes iii-v, with class iii encompassing in situ melanomas as well as other high-risk lesions such as dysplastic nevi with severe or high-grade atypia. in a study by lott et al. involving 18,715 biopsies of melanocytic lesions, 4.5% were categorized as mpath-dx class iii lesions while 8.6% were classified as class iii-v lesions.7 figure 1 summarizes the typical current care pathway and figure 2 outlines relevant aspects of the mpath-dx classification.6 a non-invasive genomic assay that detects two melanoma-associated biomarkers (the pigmented lesion assay, pla, or 2-gep test) has recently been validated as an adjunct to visual assessment in differentiating high-risk pigmented lesions appropriate for biopsy from those that are benign and suitable for clinical surveillance. in the current study, we derived the test’s ‘real-world’ npv within the intended use population using follow-up data from a large cohort of patients with pla-negative lesions. we also re-tested a separate cohort of initially pla-negative lesions to evaluate result consistency and the potential value of repeat testing for clinically evolving lesions. in addition, we determined the test’s real-world ppv and its ability to detect high-risk / mpath-dx class iii lesions using a previously-described cohort of plapositive lesions. skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 514 figure 1. current assessment and management of pigmented lesions suspected of melanoma. the traditional pathway uses visually assessed atypia to guide biopsy decisions and 83.1% of biopsies are mpath-dx class i lesions with no or mild cellular atypia based on histopathology and 8.3% being mpath-dx class ii lesions with moderate atypia.7 being able to accurately identify especially mpath-dx class iii is key to patient outcome as these lesions, designated as and high-risk, may receive a benign diagnosis while actually being true melanomas.4 currently, the proportion of surgically biopsied lesions that fall in these categories is low (4.5%).7 mpath-dx class iv and v lesions should also be referred to medical and/or surgical oncology if appropriate. data were obtained from cohorts of planegative and pla-positive lesions. planegative lesions were evaluated to determine the proportion of true negatives among negative tests, or npv, for melanoma diagnosis. pla-positive lesions were evaluated to determine the proportion of true positives among positive tests, or ppv, as well as the proportion of lesions considered high-risk / mpath-dx class iii (melanoma in situ, lesions with severe / high-grade atypia). methods skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 515 figure 2. mpath-dx classification, histopathological diagnosis, and treatment recommendations. the listed histopathologic diagnoses are common examples for the mpath-dx classes.4,6,7 pla-negative lesion study cohorts (trust study) a total of 2,104 pigmented lesions that tested pla-negative between august 2017 and august 2020 were identified for study enrollment at five geographically dispersed clinical sites. of these, 1,781 were evaluated for long-term follow-up up to 36 months after initial testing by medical chart review (figure 3). pla-negative lesions were evaluated for any melanoma diagnosis, development of later-stage disease, and melanoma death. additional 323 pla-negative lesions were enrolled in a prospective arm (nct04563949) and subjected to repeat clinical evaluation and pla testing. plapositive lesions in the repeat testing cohort were biopsied and evaluated for melanoma diagnosis. this study was approved by western and copernicus group institutional review boards and conducted according to the declaration of helsinki principles. pla-positive lesion study cohort between july 2018 and june 2019, a total of 3,418 pigmented lesions clinically suspicious for melanoma were entered in a prospective registry, evaluated and tested with the pla. the registry was conducted by 90 licensed healthcare providers within 53 practices throughout the us.8,9 of the lesions registered, 324 tested positive. pathology reports were collected and reviewed for any melanoma diagnosis. diagnoses were then categorized according to the mpath-dx classification scheme (figure 2). the ppv was determined by calculating the number skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 516 figure 3. real-world, long-term follow-up study to define the npv for the pla (trust study). pla-negative lesions were separated into 2 cohorts for long-term follow-up. 1,781 pla-negative lesions were identified by chart review and followed for up to 36 months following their initial pla test; 1,233 of these patients additionally received confirmed follow-up visits. additional 323 pla-negative lesions were prospectively enrolled into a clinical study (nct04563949) for repeat pla testing up to 24 months following the initial pla-negative test result. npv’s for both cohorts were >99%. lesions not included in the analysis were either protocol deviations (e.g. sample not collected according to the instructions for use) or lacked sufficient rna for analysis. of histopathologically confirmed melanomas among pla-positive lesions. sample collection and analysis all lesions were tested using the pigmented lesion assay (pla) (dermtech; la jolla, ca).10 non-invasive sampling occurred per the standard instructions for use with dermtech’s adhesive skin collection kit. samples were submitted to dermtech’s clia certified and cap accredited high complexity molecular pathology laboratory for gene expression testing (la jolla, ca). following the extraction of rna, samples were analyzed using quantitative pcr to assess the expression of two genes, linc00518 and prame.11,12 the pla is considered positive when one or both genes are detected; positive lesions subsequently undergo biopsy or excision for histopathologic review. pla-negative tests have no target gene expression detected and are typically monitored per standard clinical follow-up. per standard procedures, samples with insufficient rna quantity or quality and those with contamination (e.g. excessive blood or non-vellus hair) that cannot undergo gene expression analysis are reported as such and these lesions are recommended to undergo biopsy. here, we determine the real-world npv and ppv of the 2-gep pla by studying appropriate trust study cohorts (n=2,572 lesions total; focus on long-term follow-up with chart review and long-term follow-up results skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 517 with re-testing of pla-negative lesions) as well as from a registry (n=3,418 lesions) to determine the test’s real-world performance. the median age of the re-tested trust study cohort was 58 years (41.7% male, 58.3% female patients). the median age of patients in the registry was 48 years (39.2% male, 60.8% female). pla-negative lesion study cohorts a total of 2,575 clinically suspicious pigmented lesions tested with the pla were identified by chart review and used to establish pla-negative lesion study cohorts for further evaluation (n=2104, figure 3). pla-positive lesions (n=276) and samples of 195 lesions (97 which could not undergo gene expression analysis due to insufficient genomic material or contamination due to excessive hair or blood, and 98 in which medical charts were not available for review) were excluded from npv analyses. the 1,781 pla-negative lesions identified and monitored by medical charts were reviewed for a time period of up to 36 months following the initial pla-negative test. no melanoma deaths or late-stage melanoma diagnoses were reported in this planegative lesion cohort. a subset of 1,233 lesions (69%) had confirmed follow-up evaluations within the 36 months of the initial pla-negative test. ten lesions (0.8%) in this subset cohort were subsequently biopsied (an average of 15.1 months after initial negative pla) and received an early-stage melanoma diagnosis (4 in situ and 6 pt1a invasive melanomas were identified) (figure 3) establishing an npv for melanoma diagnosis of 99.2% (ci 95%= 98.4 99.6). a total of 323 pla-negative lesions were prospectively enrolled into a clinical study (nct04563949) for repeat pla testing up to 24 months following the initial pla-negative test result. twenty-one lesions were removed from subsequent testing and analysis due to protocol deviations, insufficient quantity of rna for analysis, or contamination; however, no melanoma diagnoses were reported among these 21 lesions. repeat testing was conducted on 302 (93.5%) lesions and 268 (88.7%) remained negative (figure 3). thirty-four out of 302 lesions (11.2%) were pla positive on repeat testing. all 34 plapositive lesions underwent surgical biopsy and histopathology. three of 302 (1%) of pla-positive re-tested lesions received an in situ melanoma diagnosis. all three lesions exhibited evolution or change by clinical or photographic analysis. the time from initial pla testing to repeat testing for each lesion was 13, 14, and 19 months (average 15.3 months). if the in situ melanomas identified were present at time of initial diagnosis, the npv of the original test would be 99.0% (ci 95% = 97.1 99.8). all 34 pla-positive lesions in the repeat test cohort were also categorized according to the mpath-dx classification scheme with 20 (59%) in class i, 5 (15%) in class ii, and 4 (11.8%) in class iii. the proportion of repeat tested high risk class iii lesions (11.8%) is significantly lower than the proportion of lesions in this class in primary tested lesions (26.1%). pla-positive lesion registry cohort of the 324 lesions (9.5%) that were pla positive, 316 (97.5%) underwent surgical biopsy and 313 had histopathology reports available for review. fifty-nine lesions received a melanoma diagnosis (47 in situ, 11 pt1a, and 1 pt2a) yielding a positive predictive value for melanoma diagnosis of 18.7%. using the mpath-dx risk classification scheme of melanocytic lesions to facilitate comparisons among reports from pathologists who use different nomenclature and classifications of lesion atypia, subsets of 272 melanocytic and 41 non-melanocytic skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 518 lesions (primarily scars of previously biopsied pigmented lesions and keratoses potentially constituting collision lesions with melanocytic lesions) were identified. the melanocytic lesions were further categorized per mpathdx classification scheme with 43.8% (n=119), 25.7% (n=70), 26.1% (n=71), 4.0% (n=11) and 0.4% (n=1) classified as classes i–v, respectively. similar to previously published work on the genomic progression of melanoma13, the pla identified genomic atypia across the full spectrum of categories, including some mpath-dx class i and class ii lesions. notably, 30.5% (n=83) of plapositive lesions had histopathological diagnoses corresponding to the malignant / high-risk class iii-v categories (figure 4). the proportion of lesions in class ii-v groupings of atypical pathologic features was 56.3%. biopsy burden of the 5,993 lesions tested with the pla in the lesional cohorts assessed (n=2,575 trust study and n=3,418 registry cases), the vast majority of tests were negative and not subjected to surgical biopsy. in this group 3.7% to 6.5% of pla tests could not be analyzed due to insufficient quantity of rna, contamination (e.g. hair or blood), and sample collection protocol deviations. thus, in these cohorts the pla reduced surgical biopsies by 83.5% to 86.3%. the pla (2-gep test) is intended as ‘ruleout’ test for melanoma and should therefore have a high npv within the intended use population. npv is often derived from a test’s sensitivity and specificity in conjunction with estimates of disease prevalence, but this approach may not accurately reflect the npv observed in actual clinical use. in this study, we sought to calculate ‘real-world’ npv by examining a large cohort of pla-negative lesions from five geographically dispersed clinical sites for any evidence of melanoma detected during a protracted follow-up period. within a cohort of 1,781 patients, including 1,233 patients with confirmed follow-up visits, 10 early stage melanomas (6 in situ, 4 pt1a) were identified 12-24 months after the initial testing. importantly, no late-stage melanoma diagnoses or melanoma deaths were reported. calculations restricted to the 1,233 patients with confirmed follow-up visits yielded an npv of 99.2% (ci 95% = 98.4 99.6). analysis of the entire cohort of 1,781 pla-negative lesions produced an npv of 99.4% (ci95% = 99.0 – 99.7). these results suggest the pla’s npv is superior to that of visual assessment alone (npv = 75-83%).14 to further assess npv, a separate cohort of 302 pla-negative lesions underwent clinical evaluation and repeat testing an average of approximately 15 months after initial testing. of these, 34 lesions were pla-positive upon repeat testing, three of which were interpreted histopathologically as melanomas in situ. for the calculation of npv it was assumed that these were melanomas at the time of initial testing and represent initial false-negative results. however, it is also possible they were benign lesions in which in situ melanomas subsequently evolved during the interval between initial and repeat testing (median 15.3 months). in support of this, all three lesions reportedly demonstrated evolution between initial and repeat testing. further study is warranted but this observation suggests that repeat testing may have value in the rare instance that a lesion clinically evolves and starts to resemble a more concerning higher-risk lesion after an initial negative test result. the ability to re-assess an evolving intact lesion in these rare circumstances may be seen as an additional advantage of non-invasive discussion skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 519 genomic testing over scenarios where a clinician needs to re assess changing remnants of a previously biopsied lesion. figure 4. real-world registry to define the ppv for the pla. a total of 3,418 lesions were assessed by pla, and positive melanocytic lesions with corresponding histopathology were further classified by mpath-dx.8, 9 many tests require a compromise with respect to npv and ppv in which optimizing one parameter comes at the expense of the other. maximum npv is priority for a test designed to safely rule out melanoma, but this study and prior analyses confirm that the pla’s high npv is balanced by a suitable ppv. in addition, the current data demonstrate that the pla effectively detects the subset of ostensibly benign but high-risk melanocytic lesions such as dysplastic nevi with high-grade atypia (mpath-dx class iii) that are typically excised to mitigate potential misdiagnosis and / or risk of progression. while it is obviously most important to identify and excise definitive melanomas, many authorities advocate complete excision for melanocytic lesions with high-grade atypia due to their higher potential for misdiagnosis (ambiguous histopathologic features misinterpreted as benign or focal malignancy not visualized within the available sections) and / or their increased risk for progression (propensity to evolve into melanoma over time).4,6,16,17 wachsman et al., for example, described a lesion with non-invasively detected genomic atypia that initially received a benign diagnosis but was later found to harbor melanoma upon serial sectioning.17 early-stage melanoma in particular carries an inherent risk of evading histopathologic detection since it may evolve focally within a pre-existing nevus, yet due to the practical limitations of sectioning and histopathologic examination only up to 2% of biopsied tissue may be examined microscopically.14 furthermore, early-stage melanocytic neoplasms are more likely than fully-evolved lesions to exhibit ambiguous or conflicting histopathologic features and generate skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 520 diagnostic uncertainty or discordance, increasing potential for false-negative or false-positive diagnoses.4 in this study, some lesions categorized as mpath-dx class i and ii as well as some pigmented non-melanocytic lesions produced positive test results. the significance of linc00518 and prame overexpression by non-melanocytic lesions and by melanocytic lesions that seemingly lack high-risk or overtly malignant histopathologic features is not yet fully characterized. however, genomic aberrations likely evolve prior to the development of morphologically identifiable malignancy.18 in addition, the pla samples the entire breadth of a lesion and therefore may detect small foci of malignancy not visualized within the limited portion of a biopsy specimen that can be examined by histopathology.14,16 studies in which plapositive but histopathologically-benign specimens undergo serial sectioning to evaluate the frequency of occult malignancy are ongoing. the pla is intended for analysis of clinically ambiguous lesions, those considered suspicious but not definitive for melanoma, rather than clinically obvious melanomas or banal appearing nevi. the proportion of positive tests that reveal melanoma on subsequent biopsy should therefore be heavily skewed toward in situ and pt1a melanomas if the test is being used as intended, and this was indeed demonstrated in the current study. additionally, clinical utility studies have shown high concordance between the pla result and subsequent treatment, with 97.5% of pla-positive lesions proceeding to biopsy and histopathologic evaluation and 99.99% of pla-negative lesions followed with clinical surveillance rather than biopsy.8,9 importantly, detection of genomic atypia enriches the pool of biopsied lesions for those most likely to be diagnosed as high-risk and / or fully malignant (mpath-dx class iiiv). for this group, enrichment was 3.5-fold greater than with visual atypia alone (8.6% vs. 30.5%).7 (figure 5) enrichment is achieved through substantial reduction in the overall biopsy burden (by ~85%), thereby offering a solution to the problem of overbiopsy and over-diagnosis of pigmented lesions recently highlighted by welch and colleagues.5 an important limitation of this study is that follow-up visits were not documented for 548 of the 1,781 pla-negative patients, and thus it cannot be confirmed that none of these 548 patients developed a melanoma that remained undetected or was identified and treated elsewhere. for this reason, the most definitive npv calculation is that derived from the subset of 1,233 patients with documented follow-up visits within the indicated period. in addition, retrospective medical chart review could erroneously evaluate a lesion not tested with the pla. while real-world data from lesion cohort studies are the most relevant to actual clinical practice, the strategies chosen do not allow for comparisons based on consensus histopathology reads that may reduce variability in histopathologically-determined diagnoses. lastly, pla-negative lesions that were negative on repeat testing and by clinical evaluation were considered true negatives for purposes of these analyses, and the possibility that some lesions were in fact melanomas that were negative on both the initial and repeat tests and also by clinical follow-up cannot be entirely excluded. the current study further highlights the pla’s conclusion skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 521 very high npv of 99% of critical importance to a robust rule-out test within the intended use population. it demonstrates that noninvasive detection of genomic atypia by the pla can enhance visual assessment of pigmented lesions, enabling clinicians to more effectively triage high-risk lesions to biopsy while safely managing benign lesions via clinical surveillance. this approach improves the overall npv and ppv of the current diagnostic pathway while optimizing early detection of melanoma. figure 5. implementation of the pla improves the assessment and management of pigmented lesions based on genomic atypia information. while the pla offers benefits across the spectrum of lesions clinically suspicious of melanoma, especially mpath-dx class iii high-risk lesions are generally viewed as the most diagnostically challenging where misdiagnoses may occur. it is therefore important to identify these lesions for appropriate skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 522 management decisions. the pla enriches for these lesions with fewer overall biopsies.8,9 it is of particular interest to note that the proportion of this mpath-dx class iii group is much larger with pla use (4.5% for the current care pathway summarized in figure 1 vs. 26.1% with pla use).7 by identifying these lesions as candidates for excision, the chance of a missed or delayed diagnosis is minimized and early melanoma detection is enhanced. mpath-dx class iv and v lesions should also be referred to medical and/or surgical oncology if appropriate. conflict of interest disclosures: drs. mks, bb, gp are investigators and advisors to dermtech, mks and gp are shareholders of dermtech. jr, mdh, lec and bj are employees and shareholders of dermtech. acknowledgements: the authors thank drs. michael walker (stanford university and walker biosciences) for help with statistical analyses. funding: none corresponding author: maral kibarian skelsey, md 5530 wisconsin avenue suite #820 chevy chase, md 20815 phone: 301 652-8081 fax: 301 652-8627 email: dr.maral.skelsey@mohs-md.com references: 1. howlader n, noone am, krapcho m, miller d, brest a, yu m, ruhl j, tatalovich z, mariotto a, lewis dr, chen hs, feuer ej, cronin ka (eds). seer cancer statistics review, 1975-2017, national cancer institute. bethesda, md, https://seer.cancer.gov/csr/1975_2017/, based on november 2019 seer data submission, posted to the seer web site, april 2020. 2. anderson am, matsumoto m, saul mi, secrest am, ferris lk. accuracy of skin cancer diagnosis by physician assistants compared with dermatologists in a large health care system. jama dermatol. 2018 may; 154(5):569-573. 3. nachbar f, stolz w, merkle t, cognetta ab, vogt t, landthaler m, bilek p, braun-falco o, plewig g. the abcd rule of dermatoscopy. high prospective value in the diagnosis of doubtful melanocytic skin lesions. j am acad dermatol. 1994 apr; 30(4):551-9. 4. elmore jg, barnhill rl, elder de, longton gm, pepe ms, reisch lm, carney pa, titus lj, nelson hd, onega t, tosteson ana, weinstock ma, knezevich sr, piepkorn mw. pathologists' diagnosis of invasive melanoma and melanocytic proliferations: observer accuracy and reproducibility study. bmj. 2017 jun 28;357:j2813. 5. welch hg, mazer bl, adamson as. the rapid rise in cutaneous melanoma diagnoses. n engl j med. 2021 jan 7;384(1):72-79. 6. piepkorn mw, barnhill rl, elder de, knezevich sr, carney pa, reisch lm, elmore jg. the mpath-dx reporting schema for melanocytic proliferations and melanoma. j am acad dermatol. 2014 jan;70(1):131-41. 7. lott jp, boudreau dm, barnhill rl, weinstock ma, knopp e, piepkorn mw, elder de, knezevich sr, baer a, tosteson ana, elmore jg. population-based analysis of histologically confirmed melanocytic proliferations using natural language processing. jama dermatol. 2018 jan 1;154(1):24-29. 8. brouha b, ferris lk, skelsey mk, peck g, moy r, yao z, jansen b. real-world utility of a noninvasive gene expression test to rule out primary cutaneous melanoma: a large us registry study. j drugs dermatol. 2020 mar 1;19(3):257-262. 9. brouha b, ferris lk, skelsey mk, peck g, rock j, nguyen a, yao z, howell md, jansen b, cockerell, cj genomic atypia to enrich melanoma positivity in biopsied lesions: gene expression and pathology findings from a large u.s. registry study. skin. 2021 jan; 5(1). 10. gerami p, yao z, polsky d, jansen b, busam k, ho j, martini m, ferris lk. development and validation of a noninvasive 2-gene molecular assay for cutaneous melanoma. j am acad dermatol. 2017 jan;76(1):114-120.e2. 11. luan w, ding y, ma s, ruan h, wang j, lu f. long noncoding rna linc00518 acts as a competing endogenous rna to promote the metastasis of malignant melanoma via mir-2045p/ap1s2 axis. cell death dis. 2019 nov 11;10(11):855. 12. haqq c, nosrati m, sudilovsky d, crothers j, khodabakhsh d, pulliam bl, federman s, miller jr 3rd, allen re, singer mi, leong sp, ljung bm, sagebiel rw, kashani-sabet m. the gene expression signatures of melanoma progression. proc natl acad sci u s a. 2005 apr 26;102(17):6092-7. mailto:dr.maral.skelsey@mohs-md.com https://seer.cancer.gov/csr/1975_2017/ skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 523 13. shain ah, yeh i, kovalyshyn i, sriharan a, talevich e, gagnon a, dummer r, north j, pincus l, ruben b, rickaby w, d'arrigo c, robson a, bastian bc. the genetic evolution of melanoma from precursor lesions. n engl j med. 2015 nov 12;373(20):1926-36. 14. rivers jk, rigel ds. ruling out melanoma: a practical guide to improving performance through non-invasive gene expression testing. skin therapy letter, family practice edition. 2019; 14(1): 4-6. 15. lott jp, elmore jg, zhao ga, knezevich sr, frederick pd, reisch lm, chu ey, cook mg, duncan lm, elenitsas r, gerami p, landman g, lowe l, messina jl, mihm mc, van den oord jj, rabkin ms, schmidt b, shea cr, yun sj, xu gx, piepkorn mw, elder de, barnhill rl; international melanoma pathology study group. evaluation of the melanocytic pathology assessment tool and hierarchy for diagnosis (mpath-dx) classification scheme for diagnosis of cutaneous melanocytic neoplasms: results from the international melanoma pathology study group. j am acad dermatol. 2016 aug;75(2):356-63. 16. piepkorn mw, longton gm, reisch lm, elder de, pepe ms, kerr kf, tosteson ana, nelson hd, knezevich s, radick a, shucard h, onega t, carney pa, elmore jg, barnhill rl. assessment of second-opinion strategies for diagnoses of cutaneous melanocytic lesions. jama netw open. 2019 oct 2;2(10):e1912597. 17. wachsman w, morhenn v, palmer t, walls l, hata t, zalla j, scheinberg r, sofen h, mraz s, gross k, rabinovitz h, polsky d, chang s. noninvasive genomic detection of melanoma. br j dermatol. 2011 apr;164(4):797-806. 18. elder de. melanoma progression. pathology. 2016 feb;48(2):147-54. skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 448 clinical management recommendations best practices for management of delusions of parasitosis nicholas brownstone, md1, marwa hakimi, md2, john koo, md2 1 national society for cutaneous medicine, new york, ny 2 university of california, san francisco, department of dermatology, san francisco, ca delusions of parasitosis (dop), also known as delusional infestation and the eponym morgellons disease, is a condition where a patient has a fixed false belief that he or she is infested with parasites. patients may also complain about foreign material, such as fibers, extruding from their skin. clinical encounters with patients suffering from dop can cause unease and even resentment for dermatologists whose expertise lies in identifying objective evidence of skin disease. dermatologists are usually treated deferentially by their patients and can become uncomfortable when put in a situation where they have to deliberately revolve around the patient’s thinking. this issue is exacerbated by the fact that few dermatology residency training programs offer formal training in psychodermatology, no official psychodermatology fellowship exists and there is a paucity of resources for the practicing dermatologist such as specialized clinics for these patients1. this creates a situation where a dermatologist consciously or subconsciously may feel aversion for having to deal with patients who insist that their specific ideation is a reality. furthermore, providers in the united states are now under the system of “value-based reimbursement,” meaning that physicians’ overall reimbursements are determined in large part by patient satisfaction scores. in this system, physicians may be penalized financially if their satisfaction score is below the 50th percentile compared to their peers. the total patient satisfaction score is based on the input from patients who are motivated enough to spend their time and energy rating their dermatology providers. it is well known that dop patients who are angry at their dermatology providers will be motivated to make sure that their dissatisfaction with their provider is well known, potentially causing patient satisfaction scores to plummet. therefore, even if a dermatology provider is not particularly interested in psychodermatology, it is prudent to learn a few tips regarding how to handle these patients. this, at a minimum, could help dermatologists from being globally penalized financially from these encounters. dermatologists can, with training, diagnose dop, build rapport and therapeutically treat dop patients. the evaluation of patients with suspected dop begins with a careful skin examination to exclude a true infestation or neurologic introduction diagnosis of dop skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 449 disease as the cause for the reported symptoms. every patient that presents with dop or is referred for this condition should be assumed to have a bond fide skin condition until proven otherwise. patients should undergo a full body skin exam along with possibly bacterial/fungal or viral culture and koh preparations, if indicated, of any suspected areas of infestation. at the very least, these procedures help the patient feel cared for and mitigate negative feelings the patient may have towards the provider. thus, a diagnosis of dop can only be considered after true dermatoses are ruled out following a thorough history and physical examination. patients determined to have dop are categorized according to whether they have a spontaneous disorder, i.e., primary dop, or secondary dop consequent to conditions that include illicit substance abuse or withdrawal, organic brain syndrome, schizophrenia, hyperthyroidism, and vitamin b12 deficiency, among others. primary dop is commonly seen in older, post-menopausal women while for secondary dop, the age range varies. primary dop may have to be treated by the dermatologist (as primary cases are uniformly resistant to seeing any mental health professionals), while secondary cases are best co-managed by a psychiatrist and a dermatologist. it is important to realize that both primary and secondary dop patients generally end up in the dermatologist’s office because they believe they have a skin problem and simultaneously can be aversive to any inkling of mental health or psychiatry2. the following laboratory tests may be considered in aiding to elucidate a secondary cause of dop and to establish a patient’s general health status, especially if the patient is starting a systemic medication: complete blood count with differential, serum electrolytes, liver function tests, thyroid function tests, serum calcium, serum glucose, serum creatinine, blood urea nitrogen, vitamin b12, urinalysis, toxicology screen, hiv, hepatitis c and rpr for syphilis. still, the three most useful tests in elucidating etiology are thyroid function tests, vitamin b12 level and toxicology screen. although, further data are needed, there is some evidence that dop symptomology may in part be caused by dysregulation of the dopamine transporter system (dat) as age-related loss of striatal dat is much more prominent in older woman and, as mentioned above, primary cases of dop are seen mostly in older woman3. building a strong rapport with these patients is one of the most important principles of effective management. there is a high likelihood that the patient has had several negative encounters with other physicians before their visit with you. these patients may already feel quite skeptical or even hostile towards you, even before you meet them. as such, first impressions count. before entering the room to meet a patient with a chief complaint of “parasites coming out of my skin”, take a few moments outside of the door to make sure you are in an open and positive mindset. if an adequate rapport is not established, then it does not matter if you can prescribe appropriate or effective treatment, because the patient is unlikely to accept any of your advice or fill their prescriptions. it is also important to avoid the diagnosis of “delusions of parasitosis” as either a diagnostic billing code or for the purposes of documentation. instead, we most often use the icd diagnosis of “formication” or “(cutaneous) dysesthesia.” moreover, we deliberately avoid using terms that are building rapport skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 450 offensive to the patient, such as “psychosis,” “crazy,” “psychogenic,” or “delusional” in our notes. medical records can now be accessed on demand by patients in many states without having to put a request in with medical records or their providers. using such terminology for documentation, coding and diagnosis risks undermining therapeutic rapport, which takes much effort to build with dop patients. with regard to the need to communicate to other clinicians when the patient is truly delusional and may even have bizarre delusions, a good way to communicate effectively in the medical record without using offensive terms is to use verbatim quotes of the patient’s ideation (especially the most bizarre aspects), which any reasonable practitioner can recognize as delusional. furthermore, we do not refer to our clinic as “psychodermatology clinic” or our patients as “psychodermatology patients.” patients may bring in a wide variety of samples such as bundles of dirty paper towels, plastic containers with floating material inside them, random trash, debris, or anything else that one can imagine. if this is the case, we do not dismiss the samples as this could damage rapport. however, we also do not try to put them on our microscope. instead, the patient should be thanked for bringing in the specimens, but nicely told that each specimen needs to be prepared in a very specific way as the specimens cannot adequately be analyzed without examining them under a microscope. patients should be given a few glass microscope slides (with a warning to not break them in their pocket) and told that the most critical step of slide preparation is to use “absolutely clear”, transparent, tape to fix the specimen on the slide and not to use the matted tape, which does not allow detail to be seen. this method helps to reduce the amount of material that dop patients tend to bring to the office while helping to further build trust and rapport. sometimes, patients may appear as if they are only interested in getting validation that their skin problem is caused by a parasite. the best way to handle a patient with this disposition is to shift their focus from etiology to therapy by helping them acknowledge how miserable this condition is and how much it is distressing them. their problem can be referred to as a “mysterious condition” for which no one knows the etiology, which is technically true because an exact etiology for this disease has not been delineated. rather than focusing on etiology, you can inform the patient that there is a medication which usually works very well for this condition if they are willing to be pragmatic and try it on a “trial and error” basis. at the end of the day, the patient will usually appreciate the fact that there is a chance to treat and possibly even cure their condition, and if therapy and recovery is emphasized, rather than the etiology, the patient will likely be willing to accept treatment. on the other hand, if they still insist on investigation, the patient can be referred to an infectious disease specialist, entomologist or parasitologist with the reassurance that if these providers cannot help the patient, they are always welcome back for follow up. as stressed above, it is well known that dop patients can be reluctant to accept anything that has a psychiatric indication or is linked to mental health in anyway. luckily, there is one medication, namely pimozide (orap®), which works very well for the treatment of delusions of parasitosis4. not only is pimozide efficacious, but it is uniquely acceptable to these patients due to pharmacotherapy of dop skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 451 figure 1. trapezoid dosing regimen for pimozide and risperidone the fact it has no official u.s. food and drug administration (fda) psychiatric indication: it is only indicated in the u.s. for tourette’s syndrome, which is a neurological disorder. therefore, patients who refuse all psychiatric medications are much more willing to try pimozide for this reason. the dosing strategy resembles a trapezoid (figure 1). pimozide is usually started with a very low dose of 0.5 mg to 1 mg per day. then the dose is increased by no more than 0.5 mg increments every 2-4 weeks until an efficacious dose is achieved. this dose is continued for 3-4 months before any further titrations are made. there is no absolute maximum dose however, most patients show good clinical response by the time the dose of 3 mg per day is reached. patient usually do not have recurrences if the medication is tapered slowly but if the patient experiences a recurrence, the same trapezoid dosing method can be used to treat these symptoms effectively. common side effects include sedation or increased energy. if sedation occurs, have the patient take the medication at night. if the patient experiences increased energy from the medication, they should be instructed to take it in the morning. rare side effects include stiffness and restlessness (akathisia). the same dosing strategy can be used for risperidone, an atypical antipsychotic agent which can also be used to treat dop. many dermatology providers may find it challenging seeing a patient with dop. however, these patients are most often reachable when approached in a deliberate, sympathetic and systematic manner as outlined here. understanding the rapportbuilding techniques and guidance on the use of pharmacotherapy presented here, dop is increase taper stable dose . mg starting dose increase by . mg every weeks taper by . mg every weeks or slower ( months)(clearing) conclusion skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 452 often treatable and sometimes even curable. with a certain knowledge base and skill set, these patients could become some of the most grateful seen in your practice. conflict of interest disclosures: none funding: none corresponding author: nicholas brownstone, md national society for cutaneous medicine new york, ny email: nickbrownstone34@gmail.com references: 1. patel a, jafferany m. multidisciplinary and holistic models of care for patients with dermatologic disease and psychosocial comorbidity: a systematic review. jama dermatol. 2020;156(6):686-694. doi:10.1001/jamadermatol.2020.0394 2. brownstone nd, koo j. special consideration for patients with morgellons disease, even among psychodermatology patients? jama dermatol. 2020;156(10):1142. doi:10.1001/jamadermatol.2020.2679 3. huber m, kirchler e, karner m, pycha r. delusional parasitosis and the dopamine transporter. a new insight of etiology? med hypotheses. 2007;68(6):1351-1358. doi:10.1016/j.mehy.2006.07.061 4. lorenzo cr, koo j. pimozide in dermatologic practice: a comprehensive review. am j clin dermatol. 2004;5(5):339-349. doi:10.2165/00128071-200405050-00007 skin july 2019 volume 3 issue 4 copyright 2019 the national society for cutaneous medicine 234 clinical management recommendations the role of dupilumab in managing allergic contact dermatitis andrew s. desrosiers, ma1, thy n. huynh, md2, stephen e. helms, md2, robert t. brodell, md2,3 1university of mississippi school of medicine, jackson, ms 2department of dermatology, university of mississippi medical center, jackson, ms 3department of pathology, university of mississippi medical center, jackson, ms allergic contact dermatitis (acd) is an inflammatory skin disease caused by a type iv, delayed hypersensitivity reaction to an allergen. it is a common condition that affects 15 to 20% of the general population and significantly decreases quality of life in affected patients.1,2 it demonstrates considerable variation in its clinical presentation and level of severity. the diagnosis of acd is further complicated because it can occur concomitantly with irritant contact dermatitis, contact urticaria, atopic dermatitis (ad) as well as other primary dermatoses.3 while for many decades acd was considered a cellmediated process that occurred exclusively via the th1 pathway, recent evidence suggests that contact sensitization is a hapten-specific, multifaceted process that involves adaptive cellular, humoral, and innate immune systems, involving th2, th17, and th22 cytokines.4–9 for example, nickel is typically a potent inducer of the th1 pathway, while fragrance and rubber tend to demonstrate classic “allergic” th2 polarizations with smaller th1 contributions.9 interestingly, frequent and recurrent exposure to an allergen can lead to stronger elicitation of th2-predominant responses over time.10 this deeper understanding of the varying mechanistic processes contributing to acd has led to new targets of therapy. systemic and topical steroids remain the most widely used agents to treat acd and act by nonspecifically inhibiting th0, th1, and th2 inflammation.11 antimetabolites (e.g. methotrexate, azathioprine), ifn-γ antagonists, and tnf-α antagonists have been used to block signaling cascades involved in innate immunity and the th0 and th1 pathways.11 recently, there has been vigorous debate about the value of using dupilumab, a biologic that targets th2mediated processes, in the management of recalcitrant acd. dupilumab is a human monoclonal immunoglobulin g4 (igg4) antibody approved by the us food and drug administration for the treatment of recalcitrant moderate to severe ad.12 by binding to the interleukin-4rα (il-4rα) subunit shared by the il-4 and il-13 receptor complexes, it inhibits il-4 and il-13 cytokineinduced responses, preventing the production and release of ige, what is dupilumab? skin july 2019 volume 3 issue 4 copyright 2019 the national society for cutaneous medicine 235 proinflammatory cytokines, and chemokines.12 this downregulates genes associated with epidermal proliferation and blocks the differentiation of naïve t cells via the th2 pathway.13 in 2018, puza and atwater reported a weakened patch test response in a patient taking dupilumab.14 a few months later, joshi and khan reported a patient with allergic contact dermatitis that appeared to be controlled by dupilumab after failing other systemic therapies. the patient had no personal or family history of ad but interestingly had a predominantly th2mediated response to endovascular stents containing nickel.15 chipalkatti et al later presented two patients with recalcitrant acd, multiple positive allergens on patch testing, and significant improvement with dupilumab.16 the remaining case reports and studies investigating dupilumab’s efficacy in treating acd involved patients with concomitant ad. the distinction between dupilumab’s use in acd patients with and without underlying ad is important, as acd responses are polarized toward a th2 response in the skin of ad patients.17 four studies demonstrated significant improvement in recalcitrant acd with dupilumab in a series of predominantly ad patients. three of these studies showed mean improvements ranging from 85 to 90% in the percentage of body surface area affected by acd; 17 of the 23 patients included in these studies had a history of ad.18–20 the fourth study, a retrospective chart review, demonstrated improvement with dupilumab in 64 ad patients, 31 of whom had confirmed or suspected acd. ad patients with and without acd responded equally well to dupilumab.21 in the context of underlying ad, the allergens that cause acd in dupilumab-responsive patients include balsam of peru, carba mix, cobalt, cocamidopropyl betaine, colophonium, formaldehyde, fragrance mixes 1 and 2, mercapto mix, methylchloroisothiazolinone, mixed diakyl thiourea, nickel, oleamidopropyl dimethylamine, propylene glycol, rubber, and textile dyes.15,18–20,22–24 further investigations are required to determine the full range of allergens that evoke significant type 2 immune responses in patients with and without ad. 1. not all patients with acd respond to dupilumab. crepy and colleagues reported a case in which an ad patient had acd that was driven primarily by type 1 inflammation and was not improved with dupilumab, suggesting that, even in ad patients, dupilumab is ineffective against classic th1triggered acd.25 stout and silverberg provided further evidence that dupilumab is not always an effective treatment for acd in ad patients. they presented seven cases: four patients no longer experienced flares of acd with allergen contact, while three patients continued to develop flares with allergen exposure.26 finally, if dupilumab “turned off” acd like a light switch, patch testing in ad patients controlled by this drug would be uniformly negative, and this is not the case.14,27 further, it is uncertain if dupilumab’s efficacy in treating acd in is there data supporting dupilumab as a treatment for allergic contact dermatitis? are there potential problems with choosing dupilumab treatment? skin july 2019 volume 3 issue 4 copyright 2019 the national society for cutaneous medicine 236 ad patients is due to improvement of the underlying ad and improving the skin’s barrier function against offending allergens.21 2. dupilumab has significant side effects. a meta-analysis of eight randomized controlled trials that compared dupilumab to a placebo for the treatment of ad found that patients receiving dupilumab had statistically significant increases in the incidences of conjunctivitis (rr 2.64), injectionsite reactions (rr 2.24), and headache (rr 1.47).28 these effects are not likely due to an immunosuppressive mechanism since this medication has had no known immunosuppressive activity and incidences of nasopharyngitis, upper respiratory infections, urinary tract infections, and herpes virus infections were not increased with dupilumab when compared to placebo.28,29 3. dupilumab is expensive. for acd patients who are responsive to dupilumab and are unable to avoid relevant allergens, the cost of longterm dupilumab treatment can be prohibitive. a recent study evaluating the cost of dupilumab for the treatment of ad estimated the lifetime cost for patients to be $509,600 (i.e. $267,800 in drug costs and $241,800 in other healthcare costs), exceeding the cost of usual care with emollients by $238,100.30  the cytokine polarity of the immunologic response in acd depends upon the inciting allergen, so the therapeutic approach to acd must be individualized.  a single allergen can elicit different immunological responses in patients with and without underlying ad.  there is limited evidence in support of using dupilumab for acd in patients without concomitant ad.  the cost of this drug further argues against its use in all patients with acd.  dupilumab’s benign side effect profile, particularly its lack of immunosuppression, relative to other systemic therapies make it a reasonable option in ad patients with systemic acd to certain allergens known to elicit a significant type 2 immune response who have failed other treatments. conflict of interest disclosures: robert brodell, md discloses the following potential conflicts of interest: research has been performed for glaxo smith kline, novartis, and galderma laboratories. advisory boards: intraderm pharmaceuticals. stephen helms, md, thy huynh, md, and andrew desrosiers have no relevant conflicts of interest to declare. funding: none. corresponding author: andrew s. desrosiers, ma university of mississippi school of medicine 2500 north state street jackson, mississippi, 39216 adesrosiers@umc.edu how should physicians discuss dupilumab with patients with acd? mailto:adesrosiers@umc.edu skin july 2019 volume 3 issue 4 copyright 2019 the national society for cutaneous medicine 237 references: 1. peiser m, tralau t, heidler j, et al. allergic contact dermatitis: epidemiology, molecular mechanisms, in vitro methods and regulatory aspects. current knowledge assembled at an international workshop at bfr, germany. cell mol life sci. 2012;69(5):763-781. 2. kadyk dl, mccarter k, achen f, belsito d v. quality of life in patients with allergic contact dermatitis. j am acad dermatol. 2003;49(6):1037-1048. 3. nixon rl, mowad cm, marks jg. allergic contact dermatitis. in: bolognia j, schaffer j, cerroni l, eds. dermatology. 4th ed. philadelphia: elsevier; 2018:242-261. 4. rowe a, bunker cb. interleukin-4 and the interleukin-4 receptor in allergic contact dermatitis. contact dermatitis. 1998;38(1):36-39. 5. traidl c, jugert f, krieg t, merk h, hunzelmann n. inhibition of allergic contact dermatitis to dncb but not to oxazolone in interleukin-4-deficient mice. j invest dermatol. 1999;112(4):476-482. 6. nagai h, ueda y, ochi t, et al. different role of il-4 in the onset of hapteninduced contact hypersensitivity in balb/c and c57bl/6 mice. br j pharmacol. 2000;129(2):299-306. 7. campos ra, szczepanik m, itakura a, et al. interleukin-4-dependent innate collaboration between inkt cells and b-1 b cells controls adaptative contact sensitivity. 8. immunology. 2006;117(4):536-547. 9. niiyama s, tamauchi h, amoh y, et al. th2 immune response plays a critical role in the development of nickelinduced allergic contact dermatitis. int arch allergy immunol. 2010;153(3):303-314. 10. dhingra n, shemer a, correa da rosa j, et al. molecular profiling of contact dermatitis skin identifies allergendependent differences in immune response. j allergy clin immunol. 2014;134(2):362-372. 11. kitagaki h, ono n, hayakawa k, kitazawa t, watanabe k, shiohara t. repeated elicitation of contact hypersensitivity induces a shift in cutaneous cytokine milieu from a t helper cell type 1 to a t helper cell type 2 profile. j immunol. 1997;159(5):2484-2491. 12. sung ct, mcgowan ma, machler bc, jacob se. systemic treatments for allergic contact dermatitis. dermatitis. 2019;30(1):46-53. 13. dupixent (dupilumab) injection. 2017. https://www.accessdata.fda.gov/drugs atfda_docs/label/2017/761055lbl.pdf. 14. hamilton jd, suárez-fariñas m, dhingra n, et al. dupilumab improves the molecular signature in skin of patients with moderate-to-severe atopic dermatitis. j allergy clin immunol. 2014;134(6):1293-1300. 15. puza cj, atwater ar. positive patch test reaction in a patient taking dupilumab. dermat contact, atopic, occup drug. 2018;29(2):89. 16. joshi sr, khan da. effective use of dupilumab in managing systemic allergic contact dermatitis. dermat contact, atopic, occup drug. 2018;29(5):282-284. 17. chipalkatti n, lee n, zancanaro p, dumont n, donovan c, rosmarin d. dupilumab as a treatment for allergic contact dermatitis. dermat contact, atopic, occup drug. 2018;29(6):347348. 18. correa da rosa j, malajian d, shemer a, et al. patients with atopic dermatitis have attenuated and distinct contact skin july 2019 volume 3 issue 4 copyright 2019 the national society for cutaneous medicine 238 hypersensitivity responses to common allergens in skin. j allergy clin immunol. 2015;135(3):712-720. 19. machler bc, sung ct, darwin e, jacob se. dupilumab use in allergic contact dermatitis. j am acad dermatol. 2019;80(1):280-281.e1. 20. goldminz am, scheinman pl. a case series of dupilumab-treated allergic contact dermatitis patients. dermatol ther. 2018;31(6):e12701. 21. jacob se, sung ct, machler bc. dupilumab for systemic allergy syndrome with dermatitis. dermat contact, atopic, occup drug. 2019;30(2):164-167. 22. chipalkatti n, lee n, zancanaro p, dumont n, kachuk c, rosmarin d. a retrospective review of dupilumab for atopic dermatitis patients with allergic contact dermatitis. j am acad dermatol. 2019;80(4):1166-1167. 23. collantes-rodríguez c, jiménez-gallo d, ossorio-garcía l, villegas-romero i, linares-barrios m. recall dermatitis at patch test sites in an atopic dermatitis patient treated with dupilumab. contact dermatitis. 2019;80(1):69-70. 24. huynh t, hadi s, tan k, guttmanyassky e. dupilumab therapy for chronic refractory hand dermatitis [abstract]. exp dermatol. 2018;27(s2):33. 25. zhu ga, chen jk, chiou a, ko j, honari g. repeat patch testing in a patient with allergic contact dermatitis improved on dupilumab. jaad case reports. 2019;5(4):336-338. 26. crepy m-n, nosbaum a, bensefa-colas l. blocking type 2 inflammation by dupilumab does not control classic (type 1-driven) allergic contact dermatitis in chronic hand eczema. contact dermatitis. march 2019. 27. stout m, silverberg ji. variable impact of dupilumab on patch testing results and allergic contact dermatitis in adults with atopic dermatitis. j am acad dermatol. march 2019. 28. hoot jw, douglas jd, falo ld. patch testing in a patient on dupilumab. dermatitis. 2018;29(3):164. 29. ou z, chen c, chen a, yang y, zhou w. adverse events of dupilumab in adults with moderate-to-severe atopic dermatitis: a meta-analysis. int immunopharmacol. 2018;54:303-310. 30. simpson el, bieber t, guttman-yassky e, et al. two phase 3 trials of dupilumab versus placebo in atopic dermatitis. n engl j med. 2016;375(24):2335-2348. 31. zimmermann m, rind d, chapman r, kumar v, kahn s, carlson j. economic evaluation of dupilumab for moderateto-severe atopic dermatitis: a costutility analysis. j drugs dermatol. 2018;17(7):750-756. powerpoint presentation presented at 2021 fall clinical dermatology conference, las vegas, nv, usa, october 21–24, 2021 the greater reduction in total psd score was consistent with improved psoriasis severity and burden ls mean change from baseline in bsa was significantly greater with roflumilast at all timepoints dermis-1 dermis-2 reduction in itch occurs as early as week 2 and consistently improves through week 8 about 60% of roflumilast-treated patients achieved clear intertriginous skin (i-iga = 0) at week 8 the primary endpoint was achieved in both dermis-1 and dermis-2 (week 8) introduction • no nonsteroidal topical therapies with novel mechanism of action for psoriasis have been approved in more than 20 years – available topical treatments are less than ideal, necessitating a trade-off between efficacy and tolerability1 • roflumilast is a selective and highly potent phosphodiesterase-4 inhibitor investigated as a once-daily, nonsteroidal, topical treatment for various inflammatory dermatologic conditions – in a phase 2b, randomized, double-blind, vehicle-controlled trial, roflumilast cream provided • significant and rapid improvement of psoriasis • demonstrated efficacy for intertriginous plaques • reduction of itch2 • this poster presents efficacy and safety results from dermis-1 (clinicaltrials.gov identifier: nct04211363) and dermis-2 (clinicaltrials.gov identifier: nct04211389) – these were 2 identical phase 3, randomized, double-blind, vehicle-controlled studies of once-daily roflumilast cream 0.3% in patients with psoriasis (figure 1) once-daily roflumilast cream 0.3%, a potent phosphodiesterase-4 inhibitor, provided safe and effective treatment of psoriasis in the dermis-1 and dermis-2 phase 3 trials conclusions once-daily roflumilast cream 0.3% demonstrated: • clinically meaningful efficacy in psoriasis based on iga success at the primary endpoint of 8 weeks – results were reproducible across both phase 3 studies • significant improvements in difficult-to-treat areas – significant increases in percentages of patients achieving i-iga success and i-iga status of clear • superior improvement across multiple other efficacy endpoints versus vehicle cream – onset of efficacy occurred as early as 2 weeks • in patients with psoriasis, roflumilast cream was well-tolerated with low rates of application-site aes, treatmentrelated aes, and discontinuations due to aes, comparable with that of vehicle mark lebwohl,1 leon h. kircik,2 angela y. moore,3 linda stein gold,4 james del rosso,5 zoe d. draelos,6 melinda j. gooderham,7 lawrence j. green,8 adelaide a. hebert,9 kim a. papp,10 jerry bagel,11 neal bhatia,12 laura k. ferris,13 terry jones,14 steven e. kempers,15 david m. pariser,16 paul s. yamauchi,17 matthew zirwas,18 amy feng,19 patrick burnett,19 robert c. higham,19 david r. berk19 1icahn school of medicine at mount sinai, new york, ny, usa; 2icahn school of medicine at mount sinai, new york, ny, indiana medical center, indianapolis, in, physicians skin care, pllc, louisville, ky, and skin sciences, pllc, louisville, ky, usa; 3arlington research center, arlington, tx, baylor university medical center, dallas, tx, usa; 4henry ford medical center, detroit, mi, usa; 5jdr dermatology research center, llc, las vegas, nv, usa; 6dermatology consulting services, high point, nc, usa; 7skin centre for dermatology, probity medical research and queen’s university, peterborough, on, canada; 8george washington university school of medicine, rockville, md, usa; 9ut health mcgovern medical school, houston, tx, usa; 10probity medical research and k papp clinical research, waterloo, on, canada; 11psoriasis treatment center of central new jersey, windsor, nj, usa; 12therapeutics clinical research, san diego, ca, usa; 13university of pittsburgh, department of dermatology, pittsburgh, pa, usa; 14u.s. dermatology partners bryan, bryan, tx, usa; 15minnesota clinical study center, fridley, mn, usa; 16eastern virginia medical school and virginia clinical research, inc., norfolk, va, usa; 17david geffen school of medicine at ucla, los angeles, and dermatology institute & skin care center, inc., santa monica, ca, usa; 18dermatologists of the central states, probity medical research, and ohio university, bexley, oh, usa; 19arcutis biotherapeutics, inc., westlake village, ca, usa safety • roflumilast cream demonstrated low rates of application-site adverse events (aes), treatment-related aes, and discontinuations due to aes, comparable with that of vehicle (table 3) • there were no treatment-related serious aes • few patients discontinued due to aes • application-site reactions were low • over 96% of patients in each group had no evidence of irritation at weeks 4 or 8 as assessed by the investigators methods • the primary endpoint was analyzed using a cochran-mantel-haenszel test stratified by site, baseline investigator global assessment (iga), and baseline intertriginous involvement – statistical significance was concluded at the 5% significance level (2-sided) – missing iga scores were imputed using multiple imputation • to control for multiple comparisons among the secondary endpoints, a multiplicity procedure was used – upon successful testing of the primary endpoint, the α was partitioned to test secondary endpoints results • 439 patients were enrolled in dermis-1 and 442 patients were enrolled in dermis-2 • most patients (86.2% to 91.0%) completed the studies (table 1) • baseline disease characteristics were balanced across treatment groups and similar between the 2 studies (table 2) table 2. baseline disease characteristics (itt population) dermis-1 dermis-2 roflumilast cream 0.3% (n=286) vehicle (n=153) roflumilast cream 0.3% (n=290) vehicle (n=152) psoriasis-affected bsa, mean % (sd) 6.3 (4.38) 7.4 (4.76) 7.1 (4.84) 7.7 (5.05) pasi, mean score (sd) 6.3 (3.15) 6.8 (3.70) 6.5 (3.22) 7.0 (3.52) wi-nrs, mean score (sd) 5.7 (2.75) 5.7 (2.84) 5.8 (2.61) 6.1 (2.75) wi-nrs score ≥4, n (%) 218 (76.2) 115 (75.2) 229 (79.0) 116 (76.3) psd, mean total score (sd) 72.1 (42.75) 73.4 (41.29) 69.3 (40.66) 77.4 (41.24) iga score, n (%) 2 (mild) 51 (17.8) 20 (13.1) 50 (17.2) 24 (15.8) 3 (moderate) 206 (72.0) 122 (79.7) 220 (75.9) 118 (77.6) 4 (severe) 29 (10.1) 11 (7.2) 20 (6.9) 10 (6.6) i-iga score, n (%) n=63 n=32 n=53 n=31 2 (mild) 33 (52.4) 16 (50.0) 25 (47.2) 13 (41.9) 3 (moderate) 27 (42.9) 16 (50.0) 27 (50.9) 17 (54.8) 4 (severe) 3 (4.8) 0 1 (1.9) 1 (3.2) bsa: body surface area; iga: investigator global assessment; i-iga: intertriginous-investigator global assessment; itt: intent-to-treat; pasi: psoriasis area severity index; psd: psoriasis symptoms diary; wi-nrs: worst itch-numeric rating scale; sd: standard deviation. table 1. patient disposition dermis-1 dermis-2 patients, n (%) roflumilast cream 0.3% (n=286) vehicle cream (n=153) roflumilast cream 0.3% (n=290) vehicle cream (n=152) completed 255 (89.2) 133 (86.9) 264 (91.0) 131 (86.2) prematurely discontinued 31 (10.8) 20 (13.1) 26 (9.0) 21 (13.8) reason for discontinuation withdrawal by patient 11 (3.8) 11 (7.2) 10 (3.4) 11 (7.2) physician decision 0 1 (0.7) 0 0 noncompliance 0 0 0 1 (0.7) protocol violation 1 (0.3) 0 0 0 lost to follow-up 12 (4.2) 4 (2.6) 15 (5.2) 7 (4.6) adverse event 5 (1.7) 2 (1.3) 1 (0.3) 2 (1.3) pregnancy 1 (0.3) 0 0 0 other 1 (0.3) 2 (1.3) 0 0 table 3. adverse events dermis-1 dermis-2 n (%) roflumilast cream 0.3% (n=286) vehicle cream (n=153) roflumilast cream 0.3% (n=290) vehicle cream (n=152) patients with any teae 72 (25.2) 36 (23.5) 75 (25.9) 28 (18.4) patients with any treatment-related teae 7 (2.4) 3 (2.0) 16 (5.5) 8 (5.3) patients with any serious ae 2 (0.7) 1 (0.7) 0 1 (0.7) patients who discontinued study due to ae 5 (1.7) 2 (1.3) 1 (0.3) 2 (1.3) most common teae (>2% in any group), preferred term hypertensiona 5 (1.7) 6 (3.9) 4 (1.4) 0 headache 3 (1.0) 2 (1.3) 11 (3.8) 1 (0.7) diarrhea 10 (3.5) 0 8 (2.8) 0 psoriasis 0 3 (2.0) 1 (0.3) 0 nasopharyngitis 5 (1.7) 3 (2.0) 1 (0.3) 1 (0.7) ahypertension includes synonymous terms (eg, blood pressure increased). data are presented for safety population. ae: adverse event; teae: treatment-emergent adverse event. these 2 phase 3 studies suggest roflumilast cream, an investigational once-daily, nonsteroidal topical phosphodiesterase-4 inhibitor, has the potential to address many shortcomings of existing topical treatments for plaque psoriasis references 1. elmets ca, et al. j am acad dermatol 2021;84:432-470. 2. lebwohl mg, et al. n engl j med 2020;383:229-239. acknowledgements • this study was supported by arcutis biotherapeutics, inc. • thank you to the investigators and their staff for their participation in the trial • we are grateful to the study participants and their families for their time and commitment • writing support was provided by christina mcmanus, phd, alligent biopharm consulting llc, and funded by arcutis biotherapeutics, inc. disclosures ml, lhk, am, lsg, jdr, zdd, mjg, ljg, aah, kap, jb, nb, lkf, tj, sek, dmp, psy, and mz are investigators and/or consultants for arcutis biotherapeutics, inc. and received grants/research funding and/or honoraria; af, pb, rch, and drb are employees of arcutis biotherapeutics, inc. additional disclosures provided on request. efficacy • both phase 3 studies met the primary endpoint of iga success at week 8 (figure 2) – significantly greater percentages of roflumilast-treated patients achieved iga success versus vehicle (figure 2) • roflumilast significantly increased the percentage of patients achieving intertriginous-investigator global assessment (i-iga) success and an i-iga status of clear (figure 3) 41.9 56.6 62.0 69.4 21.1 21.9 30.6 35.6 0 10 20 30 40 50 60 70 80 90 100 week 2 week 4 week 6 week 8 % o f p at ie nt s (9 5% c i) roflumilast 0.3% (n=229) vehicle (n=116) 34.9 50.2 57.8 67.5 22.0 18.0 22.2 26.8 0 10 20 30 40 50 60 70 80 90 100 week 2 week 4 week 6 week 8 % o f p at ie nt s (9 5% c i) roflumilast 0.3% (n=218) vehicle (n=115) figure 2. percentages of patients with iga success in dermis-1 and dermis-2 iga success = clear or almost clear plus ≥2-grade improvement from baseline. analyzed using a cochran-mantel-haenszel test stratified by site, baseline iga, and baseline intertriginous involvement; missing scores imputed using multiple imputations. intent-to-treat population. ci: confidence interval; iga: investigator global assessment. (a) (b) 5.9% 20.6% 33.3% 42.4% 2.1% 2.3% 6.1% 6.1% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% week 2 week 4 week 6 week 8 % o f p at ie nt s (9 5% c i) roflumilast 0.3% (n=286) vehicle (n=153) 3.3% 19.1% 25.6% 37.5% 2.1% 5.8% 4.7% 6.9% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% week 2 week 4 week 6 week 8 % o f p at ie nt s (9 5% c i) roflumilast 0.3% (n=290) vehicle (n=152) *** * *** *** *** iga success dermis-1 iga success dermis-2 *p<0.05; **p<0.01; ***p<0.0001 ** figure 3. percentages of patients achieving i-iga success and i-iga status of clear in dermis-1 and dermis-2 i-iga success = clear or almost clear plus ≥2-grade improvement from baseline. to control for multiple comparisons among the secondary endpoints, a multiplicity procedure was used. upon successful testing of the primary endpoint, the α was partitioned to test secondary endpoints. i-iga-intent-to-treat population: patients with intertriginous area involvement (i-iga severity ≥2) at baseline. observed data. ci: confidence interval; i-iga: intertriginous-investigator global assessment. (a) (b) 34.5 42.3 56.6 71.2 13.3 27.6 22.2 13.8 20.7 28.8 49.1 63.5 24.1 14.8 10.3 0 10 20 30 40 50 60 70 80 90 100 week 2 week 4 week 6 week 8 34.7 52.1 57.8 68.1 6.5 17.9 13.8 18.5 30.6 37.5 42.2 57.4 3.2 10.7 10.3 7.4 0 10 20 30 40 50 60 70 80 90 100 week 2 week 4 week 6 week 8 % o f p at ie nt s (9 5% c i) * * ** roflumilast 0.3% (n=53) vehicle (n=31) ** *** ** roflumilast 0.3% i-iga success roflumilast 0.3% i-iga clear vehicle i-iga success vehicle i-iga clear i-iga success and i-iga clear dermis-1 i-iga success and i-iga clear dermis-2 roflumilast 0.3% (n=63) vehicle (n=32) *p<0.05; **p<0.01; ***p<0.001 for i-iga success % o f p at ie nt s (9 5% c i) *p<0.05; **p<0.01; ***p<0.0001 figure 4. percentages of patients achieving pasi-75 (a, b) and pasi-90 (c, d) to control for multiple comparisons among the secondary endpoints, a multiplicity procedure was used. upon successful testing of the primary endpoint, the α was partitioned to test secondary endpoints; missing scores imputed using multiple imputations. intent-to-treat population. observed data. ci: confidence interval; pasi: psoriasis area severity index; pasi-75: 75% reduction in pasi total score from baseline; pasi-90: 90% reduction in pasi total score from baseline. figure 5. percentages of patients with wi-nrs success (≥4-point improvement in wi-nrs from baseline score of ≥4) to control for multiple comparisons among the secondary endpoints, a multiplicity procedure was used. upon successful testing of the primary endpoint, the α was partitioned to test secondary endpoints; missing scores imputed using multiple imputations. evaluated in a subset of the intent-to-treat population of patients with wi-nrs pruritus score ≥4 at baseline. observed data. ci: confidence interval; wi-nrs: worst itch-numeric rating scale. (a) (b) *** *** *** *** *** *** ** dermis-1 dermis-2 **p<0.01; ***p<0.0001 figure 7. ls mean percentage change from baseline in total psd score to control for multiple comparisons among the secondary endpoints, a multiplicity procedure was used. upon successful testing of the primary endpoint, the α was partitioned to test secondary endpoints. evaluated in the intent-to-treat population; analysis of covariance with treatment, site, baseline iga, baseline intertriginous involvement, and baseline psd score as independent variables. observed data. cfb: change from baseline; iga: investigator global assessment; ls: least squares; psd: psoriasis symptom diary; se: standard error. (a) (b) baseline week 2 week 4 week 6 week 8 baseline week 2 week 4 week 6 week 8 baseline week 2 week 4 week 6 week 8 ** baseline week 2 week 4 week 6 week 8 *** figure 6. ls mean percentage change from baseline in bsa affected by psoriasis to control for multiple comparisons among the secondary endpoints, a multiplicity procedure was used. upon successful testing of the primary endpoint, the α was partitioned to test secondary endpoints. evaluated in the intent-to-treat population; analysis of covariance with treatment, site, baseline iga, baseline intertriginous involvement, and baseline bsa as independent variables. bsa: body surface area; cfb: change from baseline; ls: least squares; pasi: psoriasis area severity index; pasi-75: 75% reduction in pasi total score from baseline; pasi-90: 90% reduction in pasi total score from baseline; se: standard error. (a) (b) baseline mean (sd) total psd score: roflumilast 0.3%: 72.1 (42.75) vehicle: 73.4 (41.29) baseline mean (sd) total psd score: roflumilast 0.3%: 69.3 (40.66) vehicle: 77.4 (41.24) dermis-1 dermis-2 ***p≤0.0001 ls m ea n % c fb (s e) 10 −10 −30 −50 −70 −100 0 −20 −40 −60 −80 −90 ls m ea n % c fb (s e) 10 −10 −30 −50 −70 −100 0 −20 −40 −60 −80 −90 100 90 80 70 60 50 40 30 20 10 0 100 90 80 70 60 50 40 30 20 10 0 endpoints primary • iga success at week 8 secondary • i-iga success • pasi-75 and pasi-90 • wi-nrs • psd • bsa safety and tolerability 8 weeks dosing visits: weeks 2, 4, 8 eligibility • diagnosis of plaque psoriasis for ≥6 months (3 months for children) • age 2+ years • iga of at least mild severity • 2–20% bsa • pasi ≥2 roflumilast cream 0.3% qd vehicle qd ra nd om iz e 2:1 n=400+ dermis-1 n=439 dermis-2 n=442 figure 1. study design bsa: body surface area; iga: investigator global assessment; i-iga: intertriginous-investigator global assessment; pasi: psoriasis area and severity index; pasi-75: 75% reduction from baseline in pasi; pasi-90: 90% reduction from baseline in pasi; psd: psoriasis symptom diary; qd: once daily; wi-nrs: worst itch-numeric rating scale. 2.2 6.1 13.1 22.4 0.7 0.8 1.5 2.3 0 10 20 30 40 50 60 70 80 90 100 week 2 week 4 week 6 week 8 % o f p at ie nt s (9 5% c i) about 40% of patients demonstrated at least a 75% improvement in psoriasis by week 8 about 20% of roflumilast-treated patients demonstrated at least a 90% improvement 0.7 5.6 8.9 17.0 0.0 0.0 0.0 2.3 0 10 20 30 40 50 60 70 80 90 100 week 2 week 4 week 6 week 8 % o f p at ie nt s (9 5% c i) 8.6 21.8 31.3 41.6 1.4 3.0 3.8 7.6 0 20 40 60 80 100 week 2 week 4 week 6 week 8 % o f p at ie nt s (9 5% c i) ** *** *** *** 2.6 16.2 28.7 39.0 1.4 3.6 3.9 5.3 0 20 40 60 80 100 week 2 week 4 week 6 week 8 % o f p at ie nt s (9 5% c i) *** *** *** dermis-1 dermis-2 * ** *** ** ** dermis-1 dermis-2 *p<0.05; **p<0.01; ***p<0.0001 percentage of patients achieving pasi-75 percentage of patients achieving pasi-90 (c) (b) (d) ** (a) *** *** *** *** *** *** *** *** • roflumilast provided statistically superior reduction of psoriasis as indicated by percentages of patients achieving psoriasis area severity index (pasi)-75 and pasi-90 (figure 4) • roflumilast provided significant reduction in itch as indicated by the worst itch-numeric rating scale (wi-nrs; figure 5) • roflumilast treatment significantly reduced body surface area affected by psoriasis (figure 6) *** • roflumilast improves disease severity and burden as indicated by significant reductions in the psoriasis symptom diary total score (figure 7) roflumilast 0.3% (n=286) vehicle (n=153) roflumilast 0.3% (n=290) vehicle (n=152) *p<0.05; **p<0.01; ***p<0.0001 *p<0.05; **p<0.01; ***p<0.0001 *p<0.05; **p<0.01; ***p<0.0001 **p<0.01; ***p<0.0001 baseline mean (sd) bsa: roflumilast 0.3%: 6.3 (4.38) vehicle: 7.4 (4.76) baseline mean (sd) bsa: roflumilast 0.3%: 7.1 (4.84) vehicle: 7.7 (5.05) *** *** *** *** *** *** **p<0.01; ***p<0.0001 **p<0.01; ***p<0.0001 0 −20 −40 −60 −80 −100 ls m ea n % c fb (s e) 0 −20 −40 −60 −80 −100 ls m ea n % c fb (s e) roflumilast 0.3% (n=286) vehicle (n=153) roflumilast 0.3% (n=290) vehicle (n=152) roflumilast 0.3% (n=286) vehicle (n=153) roflumilast 0.3% (n=290) vehicle (n=152) ***p≤0.0001 once-daily roflumilast cream 0.3%, a potent phosphodiesterase-4 inhibitor, provided safe and effective treatment of psoriasis in the dermis-1 and dermis-2 phase 3 trials << /ascii85encodepages false /allowtransparency false /autopositionepsfiles true /autorotatepages /none /binding /left /calgrayprofile (dot gain 20%) /calrgbprofile (srgb iec61966-2.1) /calcmykprofile (u.s. web coated \050swop\051 v2) /srgbprofile (srgb iec61966-2.1) /cannotembedfontpolicy /warning /compatibilitylevel 1.3 /compressobjects /off /compresspages false /convertimagestoindexed true /passthroughjpegimages true /createjobticket false /defaultrenderingintent /default /detectblends true /detectcurves 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/metadatasubject () /metadatatitle () /metricpagesize [ 0 0 ] /metricunit /inch /mobilecompatible 0 /namespace [ (adobe) (golive) (8.0) ] /openzoomtohtmlfontsize false /pageorientation /portrait /removebackground false /shrinkcontent true /treatcolorsas /mainmonitorcolors /useembeddedprofiles false /usehtmltitleasmetadata true >> ] >> setdistillerparams << /hwresolution [2400 2400] /pagesize [612.000 792.000] >> setpagedevice microsoft word may 2021 consensus 1270 proof 06032021 v7.docx skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 190 consensus statement expert consensus on sunscreen for the primary prevention of skin cancer: results from the skin cancer prevention working group conference justin w. marson, md1, aaron s. farberg, md2, alex glazer, md3, graham h. litchman, do, ms4, ryan svoboda, md, ms5, richard r. winkelmann, do6, darrell s. rigel, md, ms7, the skin cancer prevention working group 1national society for cutaneous medicine, new york, ny 2section of dermatology, baylor university medical center, dallas, tx 3dermatology science and research foundation, buffalo grove, il 4department of dermatology, st. john’s episcopal hospital, far rockaway, ny 5department of dermatology, penn state college of medicine, hershey, pa 6optumcare, los angeles, ca 7department of dermatology, nyu grossman school of medicine, new york, ny abstract background: melanoma and non-melanoma skin cancers (nmsc) are the overall most common type of malignancy. despite this fact, the use of sunscreen as a primary preventative measure for skin cancer is not ubiquitous. objective: to review the literature regarding efficacy and safety of sunscreens and to process and condense data into overarching principles to provide guidance to the public and improve outcomes for melanoma nmsc. methods: a systematic review of the literature pertaining to sunscreen efficacy in the primary prevention of melanoma and non-melanoma skin cancer, safety in humans and environmental impact was conducted. following a thorough review of the literature, the skin cancer prevention working group (scpwg), an expert panel consisting of dermatologists with specialized training in melanoma and nmsc diagnosis and management, employed a modified delphi technique to reach consensus over the development of statements regarding the current level of evidence for sunscreen efficacy and safety. final statements were only adopted after achieving a supermajority vote >80%. results: 96 articles were identified for further review and discussion. the scpwg developed 7 consensus statements regarding the efficacy and safety of sunscreens and their role in the prevention of melanoma and nmsc. conclusion: the proven benefits of primary skin cancer prevention outweigh the potential/hypothetical risks of sunscreen use, especially given insufficient real-world, prospective data for the discussed risks. as experts in skin health and skin cancer pathophysiology, the scpwg believes dermatologists are uniquely qualified to lead future studies investigating sunscreen efficacy and safety and should counsel patients and the public on skin cancer primary prevention strategies. skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 191 skin cancer (including melanoma and nonmelanoma skin cancer (nmsc)) accounts for the greatest incidence of new cancers in the us, with upwards of 200,000 cases of melanoma (~50% of which are invasive) and ~5.4 million cases of nmsc diagnosed annually.1-6 diagnosis and management of skin cancer accounts for $6 billion in yearly us healthcare expenditures.7 early diagnosis and treatment, especially for melanoma, is critical to improve patient outcomes.8,9 however, despite significant improvement in understanding of cancer pathophysiology, diagnostic armament, and treatment efficacy and modalities, over 7000 individuals in the us die from advanced melanoma annually.3,10 for this reason, one of the best forms of skin cancer management is primary prevention. one of the primary drivers of skin cancer is exposure to ultraviolet radiation (uvr).11 studies attribute 90% of melanomas to deleterious uvr-induced genetic mutations, primarily from uva radiation (320-400 nm wavelength) and uvb (280-320 nm).11 known methods to reduce harmful uvr exposure include decreasing time in direct sunlight, seeking shade, wearing darkcolored clothing, and regularly applying (and re-applying) sunscreen.12,13 the active ingredients in sunscreen are typically composed of mineral-based inorganic agents (e.g. zinc oxide (zno), titanium dioxide(tio2)) or organic compounds (e.g. oxybenzone, avobenzone, octinoxate, octisalate, homosalate, octocrylene).14 combinations of these filters are capable of broad-spectrum protection against uva and uvb.15 despite data showing the ability of these agents to reduce uvr-induced erythema and decrease longterm incidence of melanoma and nmsc, questions have arisen regarding hypothetical systemic and environmental harms of sunscreen use, including concerns that misinformation may cause unwarranted harms to patients. 16-24 the purpose of this expert consensus panel was to synthesize the most current available literature regarding sunscreen efficacy and safety into overarching principles, providing a framework with which dermatologists, physicians, and other non-physician providers may better counsel patients. literature search a systematic review of the literature pertaining to the sunscreen efficacy in the primary prevention of melanoma and nonmelanoma skin cancer and safety regarding human use and environmental impact was conducted. the medline database was queried for all relevant articles using exploded mesh terms and keywords pertaining to the themes of efficacy (incidence, mortality, primary prevention, skin cancer, melanoma, non-melanoma skin cancer, basal cell carcinoma, cutaneous squamous cell carcinoma) and safety (organic sunscreen, mineral sunscreen, oxybenzone, avobenzone, octinoxate, octisalate, homosalate, octocrylene, titanium dioxide, zinc oxide, environment, patient education, and systemic absorption). the boolean term “and” was used to find the intersection of these themes with the term “sunscreen.” 96 articles were deemed relevant to the discussion of sunscreen safety and efficacy based on full-text review were selected for further review and analysis by members of the consensus panel. introduction methods skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 192 consensus development process a 7-person consensus panel of dermatologists representing the skin cancer prevention working group (scpwg), physicians with specialized training in the diagnosis and management of melanoma and non-melanoma skin cancer, convened during may 2021. panel members discussed issues regarding the efficacy of sunscreen in skin cancer prevention and potential systemic and environmental effects given the current findings and data in the literature. statements were drafted based on review and analysis of the selected articles and relevant discussion. consensus among panel members was achieved using a modified delphi technique, which has previously been used in developing dermatologic expert panel recommendations to reach consensus.25-27 for consensus, a supermajority (>80%) agreement among participants was required. if a statement did not obtain supermajority approval, the proposal was returned to the group for modification in real-time followed by additional rounds of voting until supermajority approval was obtained. the expert consensus panel developed 7 statements that all received supermajority approval using a modified delphi technique (table 1). 1. skin cancer has a material impact on individual and public health. skin cancer (melanoma and nmsc) is the most common type of malignancy diagnosed annually, outnumbering all other cancer diagnoses ~3 to 1 with over 5.4 million new diagnoses per year and 1 in 5 americans expected to be diagnosed with a type of skin cancer by the age of 70.1-4 the incidence of skin cancer has continued to rise in the past several decades and only recently began to plateau as public outreach on sun-safety has increased.3 however, timely diagnosis and adequate management and treatment of skin cancer still account for ~$6 billion in annual healthcare expenditures.7 furthermore, despite improvements in care and diagnostic techniques, there are expected to be 7180 deaths in 2021 due to invasive melanoma alone.3,10 table 1. consensus statements statement panel in agreement 1. skin cancer has a material impact on individual and public health. 7/7 2. ultraviolet radiation is a major modifiable risk factor for skin cancer. 7/7 3. sun protective strategies, including the use of sunscreen, can reduce the risk of skin cancer. 7/7 4. adherence among the public to recommended sun protective strategies are suboptimal, especially regarding sunscreen use. 7/7 5. to date, studies have not demonstrated that sunscreens cause harm in humans. 7/7 6. there is insufficient evidence to show that sunscreens cause harm to marine ecosystems, including coral reefs. 7/7 7. the proven benefits of sunscreen usage overwhelmingly outweigh the hypothetical risks. 7/7 2. ultraviolet radiation is a major modifiable risk factor for skin cancer. up to 90% of melanomas can be directly attributed to ultraviolet radiation (uvr) exposure.11 increased frequency of sunbathing has also been found to positively correlate with a greater chance of being diagnosed with nmsc.28 artificial uvr from indoor tanning has been found to increase results skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 193 melanoma risk by as much as 20%, especially in patients under 30 years old.29 while there are multiple risk factors for skin cancer (e.g., age, gender, family history, genetics, skin phototype), modifiable risk factors, such as degree of uvr exposure, can be mitigated during a patient’s lifetime to prevent further increase in their individual risk for skin cancer.28,30-35 uvr exposure—specifically to uva radiation (320-400nm wavelength) and uvb (290-320 nm)—is a modifiable risk factor that has a material impact on skin cancer incidence.30,35 studies have demonstrated chronic intermittent uvr may preferentially influence the risk of developing melanoma while chronic sustained uvr may be more related to the development of nmsc.36,37 3. sun protective strategies, including the use of sunscreen, can reduce the risk of skin cancer. there are several sun protective strategies that reduce uvr exposure including wearing sunglasses, dark-colored/long-sleeved clothing, and a hat, seeking shade, wearing sunscreen with a sun protection factor of at least 30 (spf 30+) and potentially staying indoors between 10:00 am and 4:00 pm (depending on uvr intensity).38 sunscreen remains one of the most common and effective methods of reducing uvr exposure. large scale, longitudinal randomized-control studies have found that daily application of spf 15 sunscreen significantly reduced the number of clinically and histologically identified cutaneous squamous cell carcinomas (cscc) within a 4.5 year period (hazard ratio 0.61, 95% confidence interval 0.46-0.81) and even further specifically among histologically-confirmed cscc (hr 0.48, 95%ci 0.35-0.64).39 additional followup over 8 years found a consistently significant decrease in incidence of cscc as well as a trend towards decreasing the number of basal cell carcinomas (bcc) with daily spf 15 sunscreen.40 the authors noted that protection afforded by the spf 15 sunscreen and relatively short follow-up period may have been insufficient for more thorough analysis regarding bccs.39,40 additional subset analysis of the original study also found a significant decrease in new primary invasive melanomas over 14.5 years (hr 0.27, 95%ci 0.08-0.97).41 the sun protection factor (spf) is a measure of a sunscreen’s “strength”, with higher spf ratings indicating increased ability to block more uvb.42,43 the american academy of dermatology (aad) recommends everyone (regardless of age, gender, or race) use broad-spectrum, waterresistant sunscreens rated spf 30+.13 however data have shown higher spf may yield additional benefits. for example, spf 60 reduces the amount of uvr transmitted to the skin by an additional 50% compared to spf 30, thereby reducing potential chance at mutational events, and reducing clinically significant sunburns.43 split-face trials, where spf 100 was applied to half the face and spf 50+ applied to the other half, demonstrated significantly reduced sunburns where spf 100 sunscreen was applied.44,45 of note, although concerns have also been raised that higher spf sunscreens may provide a false sense of security and increase exposure to uvr,46,47 a randomized-controlled trial demonstrated that higher spf sunscreens did not alter sunbathing exposure but did significantly reduce incidence of sunburn48. skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 194 4. adherence among the public to recommended sun-protective strategies are suboptimal, especially regarding sunscreen use. despite solar radiation being classified as a carcinogen by the world health organization (who), up to 80.6% of individuals including up to 55.3% of patients with previously diagnosed nmsc self-report poor adherence to multi-modal sun protection guidelines.49,50 studies have found that even among patients with diagnosed melanoma, adherence to sunprotective strategies only improves transiently and then diminishes after a year, at which point it may even worsen compared to baseline.51,52 to achieve the optimal uvr protection, the us food and drug administration (fda) evaluates sunscreen applied at a density of 2 mg/cm2.14 equal protection in actual-usage settings requires approximately 1 oz of sunscreen to be applied to the entire body.13 however, under real-world conditions, patients may apply as little as 20-50% of this recommended amount.53 these figures are further diminished when considering on average not allowing enough time is given for sunscreens to settle after application (~20 minutes) prior to exposure.53 furthermore, a majority of individuals do not re-apply sunscreen within the recommended timeframe (~2-3 hours) especially after activities that may remove sunscreen (e.g. swimming, excess friction from clothing or sand).54-56 however, some of this loss of effectiveness may be offset through the usage of higher spf sunscreens may partially compensate for poor application technique and adherence.57,58 underutilization is often exacerbated by additional barriers including increased application challenges, poor comprehension of the risk of extensive uvr exposure, belief that tan skin appeared healthier, belief that sunscreen was harmful to the skin, or belief that sunscreens negatively impacts systemic vitamin d levels.59 5. to date, studies have not demonstrated that sunscreens cause harm in humans. two small-scale randomized control trials found that, under theoretical maximal-use conditions when several organic sunscreen components were applied in excess of 2-5 times real-world amounts (2 mg/cm2) in a controlled indoor setting, serum concentrations exceeded the arbitrary “generally recognized as safe and effective” (grase) amount of 0.5 ng/ml proposed by the fda.21,22 of note, the authors of this study reported no serious treatmentemergent adverse effects and also concluded that, while further studies are suggested, their findings should not deter from the use of sunscreens.22 inconsistent findings from animal studies, including rodent models, have raised concerns organic sunscreen agents may potentially disrupt endocrine function.23 one study found pregnant rats fed oral forms of oxybenzone in excess of 1605.5-7178.5 mg/kg had significantly reduced body weight, increased liver and kidney weight and no statistical difference in sex ratio or weights of offspring.60 a separate study found rats fed up to 1525 mg/kg of oxybenzone for 4 days had increased uterine weight.61 importantly, a study determined the quantity of sunscreen required to reach equivalent body-weight standardized dose.62 at the recommended 2mg/cm2 applied over the entire body surface area of an average human adult, it would take 34.6 years of daily application to reach equivalent systemic concentrations.62 however, when approximating real-world conditions in which only 50% of the skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 195 recommended amount of sunscreen (1 mg/cm2) is applied to the face, neck, hands, and arms, it would take over 277 years to achieve similar doses orally administered to rats.62 a systematic review found only 1 randomized-control trial in humans investigating sunscreen use. this trial found no association between oxybenzone and follicle-stimulating hormone (fsh), luteinizing hormone (lh), steroid-hormone binding globulin (shbg), testosterone, estradiol, or inhibin b after accounting for physiologic variations.63 of the additional 10 additional human studies that were reviewed, only 2 found potential statistically—but not clinically—significant associations with oxybenzone.64,65 one study found that high maternal urine concentration of oxybenzone significantly correlated with 2.7-3.2 day decrease in gestation period during pregnancy, but did not affect birth weight nor body length.64 a prospective cohort study found maternal oxybenzone urinary concentrations were significantly associated with increased birth weight in males and decreased birth weight in females but no association with birth length.65 importantly, neither study reported if subjects’ oxybenzone exposure was from sunscreen usage.64,65 studies have found that inorganic mineral agents (e.g., titanium dioxide (tio2), zinc oxide (zno)) poorly penetrate the stratum corneum with less than 0.03% of zno nanoparticles and no tio2 able to penetrate the upper stratum corneum, thereby limiting systemic absorption.66-68 further improvements in particle micronization have also improved cosmesis while also minimizing theoretical ability for mineral agents to induce the formation of free radicals.69-71 finally, randomized-controlled trials have also found no evidence that real-world sunscreen usage negatively impacted physiologic vitamin d production.73-75 for individuals who strictly adheres to ideal sun protective measures, studies have found oral vitamin d supplements provide adequate, affordable supplementation.76 overall, there are no studies that definitively that show sunscreens including any of the 8 most common organic sunscreen agents (oxybenzone, avobenzone, octinoxate, octisalate, homosalate, octocrylene) cause systemic harms in humans. 6. there is insufficient evidence to show that sunscreens cause harm to marine ecosystems, including coral reefs. as of january 2021, hawaii has banned the sale of organic sunscreen agents oxybenzone and octinoxate and additional bills are being considered to ban avobenzone and octocrylene by 2023 (in the absence of a prescription).24,77 these laws follow findings suggesting organic sunscreen agents were present in seawater around hawaii, were difficult to remove/process in wastewater, and had the potential to bleach/ossify coral reefs in vitro.78-80 importantly, a study found that concentrations of organic sunscreen agents were materially higher in metropolitan water supplies (likely secondary to commercial/industrial run-off) than near recreational water sources.20 furthermore, studies found that actual oxybenzone concentrations in surrounding hawaiian seawaters to be approximately 100-1000 times less concentrated than the in vitro concentrations toxic to species of microalgae, plankton, and zebrafish.20,81-82 another important consideration is that potential environmental impacts of sunscreens may be confounded by other skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 196 factors, primarily climate change. studies have demonstrated significant correlation between increasing global and ocean temperature that stress coral-algae symbiosis and stifle coral resiliency, inducing coral bleaching.83-85 additionally, while studies have found that oxybenzone had higher concentration in fish relative to seawater, there have not been any correlation with human health.86 finally, environmental-focused studies have found no evidence in real-world settings that inorganic mineral-based sunscreen agents could induce lasting damage to marine ecosystems.24,66 overall, there are no direct in-vivo findings suggesting that mineral-based inorganic or any of the 8 most common organic sunscreen agents (oxybenzone, avobenzone, octinoxate, octisalate, homosalate, octocrylene) cause harm to marine ecosystems. 7. the proven benefits of sunscreen usage overwhelmingly outweigh the hypothetical risks. studies have consistently shown that regular sunscreen usage is capable of reducing the incidence of melanoma and nmsc.39-41,44-46 sunscreens can also prevent actinic damage and skin aging as well as ameliorate photodermatoses and photosensitive conditions.87-89 in contrast, a majority of studies proposing hypothetical risks with sunscreen usage filters in controlled settings in concentrations far beyond what is commercially available to purposefully induce pathologic responses in animal models and the environment.20,6062,81,82 under real-world conditions, these same pathologic responses have not been replicated. the panel also noted that realworld, prospective trials are simulated every weekend, on holidays, and even daily depending on local climate and season, as millions of individuals apply sunscreen without clinically appreciable adverse effects. sunscreens are an efficacious and integral component in the primary prevention of melanoma and nmsc. studies have consistently shown that sunscreens are able to decrease incidence of nmsc and melanoma, with higher spf-rated sunscreens being more capable of reducing sun burns and amount of uvr transmitted to the skin. unfortunately, due to a combination of inaccurate health and science literacy and misinformation campaigns, high-risk, vulnerable patients may be dissuaded from utilizing appropriate sun-protective measures, including sunscreen.90,91 sunburns continue to be prevalent beyond the non-hispanic white population, also affecting younger adults, patients on chronic immunosuppressive therapy and 13% of black and 30% of hispanic americans.92,93 even patients diagnosed with melanoma or nmsc have demonstrated poor long-term adherence to sun-protective measures.50-52 frequently reported barriers to using sunscreen and sun-protective strategies include increased application challenges, cosmetic acceptability (especially with thicker products), or poor understanding of the risks of extensive uvr exposure.59 in the authors’ opinion, these barriers are only exacerbated by third party evaluators that potentially have a financial interest in recommending specific sunscreen products.90,94 for all of these reasons, the scpwg believes that dermatologists are uniquely qualified to advocate for patients and educate the general public on the importance of sun-protective strategies.95,96 discussion skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 197 the scpwg panel also noted inconsistencies and deficiencies in some of the sunscreen literature and supports further research to cultivate evidenced-based guidelines. future studies should evaluate the longitudinal efficacy of higher spf sunscreens in randomized-controlled trials, especially given improvements in broadspectrum coverage and formulations since the prior studies that demonstrated skin cancer prevention efficacy.39-41 additionally, prospective studies in real-world settings regarding sunscreen agents and any impact they may have systemically in humans or on the environment could provide more definitive evidenced-based data to improve patient counseling. with over 200,000 new cases melanoma and 5.4 million cases of nmsc in the us annually, accounting for over $6 billion in yearly healthcare expenditures, skin cancer poses a significant impact on both individual and public health. primary prevention of skin cancer continues to be of utmost importance to reduce incidence, especially in melanoma prevention given over 7000 americans continue to die annually from this cancer despite significant advancements in therapy. as experts in the diagnosis and management of skin cancers, dermatologists are especially well-equipped to discuss with patients the risks of uvr exposure and skin cancer and benefits of multimodal sun-protective measures, including the regular and proper use of sunscreens. it is hoped that these consensus statements can serve as a basis for future health and public education initiatives. dermatologists must continue to advocate for their patients by being involved in original investigations into the efficacy and safety of sunscreens and by educating the public on the nuances and merits of scientific findings in this space. conflict of interest disclosures: jwm, af, ag, ghl, rs, and rrw have no relevant disclosures. dsr serves as a consultant for beiersdorf and proctor & gamble. funding: none skin cancer prevention working group: the skin cancer prevention working group is a multi-center collaboration of experts dedicated to the prevention of skin cancer. the working group consists of clinical and research specialists that have spent years investigating and understanding the diagnosis and management of melanoma and nonmelanoma skin cancer. the mission of the working group is to cultivate and analyze evidence-based research to better understand skin cancer pathophysiology, treatment, and prevention to be leaders in skin health education. corresponding author: justin w. marson, md national society for cutaneous medicine 35 east 35th st, #208 new york, ny 10016 fax: 732-802-7207 email: justin.w.marson@gmail.com references: 1. key statistics for basal and squamous cell skin cancer. american cancer society. https://www.cancer.org/cancer/basal-andsquamous-cell-skin-cancer/about/keystatistics.html. accessed 20 april, 2021. 2. key statistics for melanoma skin cancer. american cancer society. https://www.cancer.org/cancer/melanoma-skincancer/about/key-statistics.html. accessed 20 april, 2021. 3. siegel, r.l., miller, k.d., fuchs, h.e., jemal, a., 2021. cancer statistics, 2021. ca: a cancer journal for clinicians 71, 7–33.. doi:10.3322/caac.21654 4. stern rs. prevalence of a history of skin cancer in 2007: results of an incidence-based model. arch dermatol. 2010 mar;146(3):279-82. doi: 10.1001/archdermatol.2010.4. pmid: 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(2018). photodermatology, photoimmunology & photomedicine. doi:10.1111/phpp.12417 29. ghiasvand r, rueegg cs, weiderpass e, et al. indoor tanning and melanoma risk: long-term evidence from a prospective population-based cohort study. am j epidemiol 2017;185(3):147–56.a 30. carr s, smith c, wernberg j. epidemiology and risk factors of melanoma. surg clin north am. 2020 feb;100(1):1-12. doi: 10.1016/j.suc.2019.09.005. epub 2019 nov 4. pmid: 31753105. 31. kim dp, kus kjb, ruiz e. basal cell carcinoma review. hematol oncol clin north am. 2019 feb;33(1):13-24. doi: 10.1016/j.hoc.2018.09.004. pmid: 30497670. 32. gilaberte y, casanova jm, garcía-malinis aj, arias-santiago s, garcía de la fuente mr, pamiésgracia m, ramirez-palomino j, ruiz-campos i, gracia-cazaña t, buendia-eisman a. skin cancer prevalence in outdoor workers of ski resorts. j skin cancer. 2020 jan 28;2020:8128717. doi: 10.1155/2020/8128717. pmid: 33. heltoft kn, slagor rm, agner t, bonde jp. metal arc welding and the risk of skin cancer. int arch occup environ health. 2017 nov;90(8):873-881. doi: 10.1007/s00420-017-1248-5. epub 2017 aug 1. pmid: 28766013; pmcid: pmc5640727. 34. nadhan ks, chung cl, buchanan em, shaver c, shipman s, allawh rm, hoffman ml, lim g, abdelmalek m, cusack ca. risk factors for keratinocyte carcinoma skin cancer in nonwhite individuals: a retrospective analysis. j am acad dermatol. 2019 aug;81(2):373-378. doi: 10.1016/j.jaad.2019.01.038. epub 2019 jan 2 35. suppa m, gandini s, njimi h, bulliard jl, correia o, duarte af, peris k, stratigos aj, nagore e, longo mi, bylaite-bucinskiene m, karls r, helppikangas h; euromelanoma working group,, del marmol v. association of sunbed use with skin cancer risk factors in europe: an investigation within the euromelanoma 36. nagore e, hueso l, botella-estrada r, et al. smoking, sun exposure, number of nevi and previous neoplasias are risk factors for melanoma in older patients (60 years and over). j eur acad dermatol venereol 2010;24(1):50–7. 37. schmitt j, seidler a, diepgen tl, et al. occupational ultraviolet light exposure increases the risk for the development of cutaneous squamous cell carcinoma: a systematic review and meta-analysis. br j dermatol 2011;164(2):291–307. 38. li h, colantonio s, dawson a, lin x, beecker j. sunscreen application, safety, and sun protection: the evidence. j cutan med surg. 2019 jul/aug;23(4):357-369. doi: 10.1177/1203475419856611. epub 2019 jun 20. pmid: 31219707. 39. green a, williams g, neale r, hart v, leslie d, parsons p, marks gc, gaffney p, battistutta d, frost c, lang c, russell a. daily sunscreen application and betacarotene supplementation in prevention of basal-cell and squamous-cell carcinomas of the skin: a randomised controlled trial. lancet. 1999 aug 28; 40. van der pols jc, williams gm, pandeya n, logan v, green ac. prolonged prevention of squamous cell carcinoma of the skin by regular sunscreen use. cancer epidemiol biomarkers prev. 2006 dec;15(12):2546-8. doi: 10.1158/1055-9965.epi06-0352. epub 2006 nov 28. pmid: 17132769. 41. green ac, williams gm, logan v, strutton gm. reduced melanoma after regular sunscreen use: randomized trial follow-up. j clin oncol. 2011 jan 20;29(3):257-63. doi: 10.1200/jco.2010.28.7078. epub 2010 dec 6. pmid: 21135266. 42. sun protection factor (spf). fda center for drug evaluation and research. https://www.fda.gov/about-fda/center-drugevaluation-and-research-cder/sun-protection-factorspf. accessed 23 april 2021. 43. mancuso, j.b., maruthi, r., wang, s.q. et al. sunscreens: an update. am j clin dermatol 18, 643–650 (2017). https://doi.org/10.1007/s40257-017-0290-0 44. kohli i, nicholson cl, williams jd, lyons ab, seo i, maitra p, tian x, atillasoy e, lim hw, hamzavi ih, greater efficacy of spf 100+ sunscreen compared to spf 50+ in sunburn prevention during five consecutive days of sunlight exposure: a randomized, double-blind clinical trial, journal of the american ac 45. williams jd, maitra p, atillasoy e, wu mm, farberg as, rigel ds. spf 100+ sunscreen is more protective against sunburn than spf 50+ in actual use: results of a randomized, double-blind, splitface, natural sunlight exposure clinical trial. j am acad dermatol. 2018 may;78(5):902-910.e2. doi: 10.1016/j.jaa 46. autier p, doré jf, négrier s, liénard d, panizzon r, lejeune fj, guggisberg d, eggermont am. sunscreen use and duration of sun exposure: a double-blind, randomized trial. j natl cancer inst. 1999 aug 4;91(15):1304-9. doi: 10.1093/jnci/91.15.1304. pmid: 10433619. skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 200 47. autier p, doré jf, reis ac, et al. sunscreen use and intentional exposure to ultraviolet a and b radiation: a double blind randomized trial using personal dosimeters. br j cancer. 2000;83(9):12431248. doi:10.1054/bjoc.2000.1429 48. dupuy a, dunant a, grob jj; réseau d'epidémiologie en dermatologie. randomized controlled trial testing the impact of high-protection sunscreens on sun-exposure behavior. arch dermatol. 2005 aug;141(8):950-6. doi: 10.1001/archderm.141.8.950. pmid: 16103322. 49. ultraviolet radiation. global health observatory (gho) data. https://www.who.int/gho/phe/ultraviolet_radiation/en /#:~:text=one%20in%20every%20three%20cancers ,recently%20from%20artificial%20tanning%20sunb eds. accessed 26 april 2021. 50. fischer ah, wang ts, yenokyan g, kang s, chien al. sunburn and sun-protective behaviors among adults with and without previous nonmelanoma skin cancer (nmsc): a population-based study. j am acad dermatol. 2016 aug;75(2):371-379.e5. doi: 10.1016/j.jaad.2016.02.1236. epub 2016 may 16. pmid: 27198078; pmcid 51. novak cb, young ds, lipa je, neligan pc. evaluation of sun protection behaviour in patients following excision of a skin lesion. can j plast surg. 2007 spring;15(1):38-40. doi: 10.1177/229255030701500106. pmid: 19554129; 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(2021). https://www.capitol.hawaii.gov/measure_indiv.aspx? billtype=hb&billnumber=102&year=2021 78. balmer me, buser hr, müller md, poiger t. occurrence of some organic uv filters in wastewater, in surface waters, and in fish from swiss lakes. environ sci technol. 2005 feb 15;39(4):953-62. doi: 10.1021/es040055r. pmid: 15773466. 79. brausch jm, rand gm. a review of personal care products in the aquatic environment: environmental concentrations and toxicity. chemosphere. 2011 mar;82(11):1518-32. doi: 10.1016/j.chemosphere.2010.11.018. epub 2010 dec 23. pmid: 21185057. 80. downs ca, kramarsky-winter e, segal r, fauth j, knutson s, bronstein o, ciner fr, jeger r, lichtenfeld y, woodley cm, pennington p, cadenas k, kushmaro a, loya y. toxicopathological effects of the sunscreen uv filter, oxybenzone (benzophenone-3), on coral planulae and cultured primary cells and its environmental contamination in hawaii and the u.s. virgin islands. arch environ contam toxicol. 2016 feb;70(2):265-88. doi: 10.1007/s00244-0150227-7. pmid: 26487337. 81. du y, wang wq, pei zt, ahmad f, xu rr, zhang ym, sun lw. acute toxicity and ecological risk assessment of benzophenone-3 (bp-3) and benzophenone-4 (bp-4) in ultraviolet (uv)-filters. int j environ res public health. 2017 nov 19;14(11):1414. doi: 10.3390/ijerph14111414. pmid: 29156601; pmcid: pmc5708053. 82. mitchelmore cl, he k, gonsior m, hain e, heyes a, clark c, younger r, schmitt-kopplin p, feerick a, conway a, blaney l. occurrence and distribution of uv-filters and other anthropogenic contaminants in coastal surface water, sediment, and coral tissue from hawaii. sci total environ. 2019 jun 20;670:398-4 83. cheng l, abraham j, hausfather z, trenberth ke. how fast are the oceans warming? science. 2019 jan 11;363(6423):128-129. doi: 10.1126/science.aav7619. erratum in: science. 2019 mar 8;363(6431): pmid: 30630919. 84. slattery m, pankey ms, lesser mp. annual thermal stress increases a soft coral's susceptibility to bleaching. sci rep. 2019 may 30;9(1):8064. doi: 10.1038/s41598-019-44566-9. pmid: 31147567; pmcid: pmc6542812. 85. authority gbrmp, final report: 2016 coral bleaching event on the great barrier reef, gbrmpa, townsville, 2017. 86. gago-ferrero p, díaz-cruz ms, barceló d. an overview of uv-absorbing compounds (organic uv filters) in aquatic biota. anal bioanal chem. 2012 nov;404(9):2597-610. doi: 10.1007/s00216-0126067-7. epub 2012 jun 6. pmid: 22669305. 87. hughes mc, williams gm, baker p, green ac. sunscreen and prevention of skin aging: a randomized trial. ann intern med. 2013 jun 4;158(11):781-90. doi: 10.7326/0003-4819-158-11201306040-00002. pmid: 23732711. 88. schleyer v, weber o, yazdi a, benedix f, dietz k, röcken m, berneburg m. prevention of polymorphic light eruption with a sunscreen of very high protection level against uvb and uva radiation under standardized photodiagnostic conditions. acta derm venereol. 2008;88(6):555-60. doi: 10.2340/00015555-0509. 89. oakley am, badri t, harris bw. photosensitivity. 2020 aug 10. in: statpearls [internet]. treasure skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 202 island (fl): statpearls publishing; 2021 jan–. pmid: 28613726. 90. glazer, a. m., svoboda, r. m., teplitz, r. w., & rigel, d. s. (2018). editorial: overcoming consumer challenges in sunscreen selection. skin the journal of cutaneous medicine, 2(3), 168–171. https://doi.org/10.25251/skin.2.3.3 91. prado g, svoboda rm, teplitz rw, farberg as, rigel ds. patient knowledge of fda-mandated sunscreen labeling terminology: a cross-sectional survey. photodermatol photoimmunol photomed. 2019 may;35(3):141-147. doi: 10.1111/phpp.12437. epub 2018 nov 22. pmid: 30383894. 92. holman dm, ding h, guy gp jr, watson m, hartman am, perna fm. prevalence of sun protection use and sunburn and association of demographic and behaviorial characteristics with sunburn among us adults. jama dermatol. 2018 may 1;154(5):561-568. doi: 10.1001/jamadermatol.2018.0028. pmid: 29541756; pmcid: pmc 93. tabatabaie s, litt js, crane la. the experience of outdoor physical activity for skin cancer survivors: understanding the importance of the built and natural environments. j cancer surviv. 2020 oct;14(5):739-756. doi: 10.1007/s11764-02000889-5. epub 2020 jun 6. pmid: 32506221. 94. varedi, a., wu, y. p., klein, s. z., leachman, s. a., & grossman, d. (2018). mineral sunscreens not recommended by consumer reports: what lies beneath the surface? journal of the american academy of dermatology. doi:10.1016/j.jaad.2018.09.009 95. cartee tv, alam m, armbrecht es, behera a, lawrence n, bordeaux js, baum cl, rossi a, maher ia. patient-centered outcomes for skin cancer management: utilization of a patient delphi process to identify important treatment themes. dermatol surg. 2019 feb;45(2):246-253. doi: 10.1097/dss.0000000000001756. p 96. jin j. behavioral counseling for skin cancer prevention. jama. 2018 mar 20;319(11):1176. doi: 10.1001/jama.2018.1624. pmid: 29558553. powerpoint presentation research poster presentation design © 2019 www.posterpresentations.com introduction: hair loss in women increases with age and menopause. the most common diagnosis is female pattern hair loss, also known as androgenetic alopecia, which affects an estimated 40% of women over 60. hormonal changes of menopause are associated with decreased hair growth rate as well as percentage of hairs and time spent in anagen phase. here, we present results of a 12-month study assessing the efficacy of a nutraceutical supplement in promoting and improving growth of hairs in perimenopausal, menopausal and postmenopausal women with self-perceived thinning hair. glynis ablon md faad, ablon skin institute research center, manhattan beach, ca sheryl berkowitz ms, sophia kogan, md and isabelle raymond, phd nutraceutical wellness, inc, new york, ny long-term efficacy of a nutraceutical supplement for promoting hair growth in perimenopausal, menopausal and postmenopausal women with self-perceived thinning hair methods seventy (70) females, age 40-65, who are perimenopausal, menopausal or post-menopausal with self-perceived thinning hair were enrolled in the study. results conclusion with progressive aging of society and the fact that women now spend approximately one-third of their lives in the postmenopausal period, research into interventions for menopausal symptoms including hair thinning are needed, especially since therapeutic options are so limited. the results of this study showed significant and progressive improvements in hair growth during 6 and 12 months, demonstrating the ability of a nutraceutical supplement to effectively improve hair growth and quality in peri-, menopausal and postmenopausal women with thinning hair. reference: 1ablon g, kogan, s. a randomized, double-blind, placebo-controlled study of a nutraceutical supplement for promoting hair growth in perimenopausal, menopausal, and postmenopausal women with thinning hair. j drugs dermatol. 2021;20:55-61. conflicts of interest/disclosure: dr. glynis ablon received a research grant for the study from nutraceutical wellness llc. all other authors are employees by nutraceutical wellness llc study design results 6m and 12m analyses based on 60 subjects; • 33 active • 27 placebo subjects average age of 55.15 (±6.57) years. no differences between groups in terms of; • demographics, • general lifestyle; or • menopausal symptoms. previously reported1 interim 6-month results showed statistically significant improvements for the active group vs placebo for the number of terminal, vellus and total hairs and shedding at day 90 with further improvement at day 180 (all ps <0.005). blinded investigator global hair assessments revealed progressive and significant improvement for the active group vs the placebo group at day 180 on both hair growth and quality scales (p<0.05). the purpose of the study was to assess the safety and efficacy of an oral supplement with standardized botanicals in improving hair growth in perimenopausal, menopausal and post-menopausal female subjects with self-perceived thinning hair; • 6-month double-blind, randomized, placebo-controlled • 6-month open-label extension at each visit: • phototrichograms were obtained of the target area via macrophotography for hair count analysis. • hair wash shed count. • two-dimensional standardized global photographs of the entire head, hair and target region and used to assist the blinded investigator in grading general hair growth and hair quality (texture, shine, dryness, scalp coverage, hair brittleness and overall appearance) improvement from baseline. figure 1: global photographs of profile views of an active subject at baseline, day 90, day 180 and day 360. top: global photographs of top view bottom: macrophotographs of selected 1 cm2 target area secondary endpoints include; • hair wash shedding counts • blinded physician global hair assessments • subject questionnaires among subjects in the active treatment group for 12 consecutive months: • mean total hair counts increased significantly and progressively from day 0 to 360, culminating in a mean increase of 11.7% (p<0.0001). • mean terminal hair counts progressively increased from day 0 to day 360, corresponding to a significant 13.4% improvement (p<0.0001). • shedding significantly decreased by 43.2% on day 180 (p<0.01), remaining stable through day 360 (p<0.01 vs. baseline) • global hair growth improvement ratings increased significantly 43% from day 90 to 180 (p<0.001) and 25% from day 90 to 360 (p<0.05). • global hair quality improvement ratings significantly increased by 24% from day 90 to 180 (p<0.05) and by 37% from day 90 to 360 (p<0.005). a 13% increase was noted from day 180 to 360 but was not statistically significant when switched over to the active treatment, subjects initially in the placebo group had: • 5.1% increase in hair growth (p<0.001) • 39% decrease in shedding (p<0.0001) from day 180 to 360. • global hair growth improvement ratings across 6-month of active treatment for this group increased by 30% (p<0.05) versus 11% when they were taking placebo (p>0.05). • global hair quality improvement ratings significantly increased by 40% (p<0.001) versus 11% when they were taking placebo (p>0.05). safety assessment: daily administration of the nutraceutical supplement was well-tolerated. there were no unanticipated aes. primary endpoints included change in the number of: evaluated at d90, 180, 270 and 360 via macrophotography • total hair count • terminal hair count • vellus hair count 66 68 70 72 74 76 baseline 6 month n u m b e r o f h a ir s mean change in terminal hair counts: initial placebo group vs when switched to active treatment for 6 months initial placebo group switched to active treatment day 0 day 180 day 360 66 68 70 72 74 76 78 day 0 day 90 day 180 day 360 n u m b e r o f h a ir s change in terminal hair counts across 12 months of active treatment skin july 2019 volume 3 issue 4 copyright 2019 the national society for cutaneous medicine 239 original research establishing an evidence-based decision point for clinical use of the 31-gene expression profile test in cutaneous melanoma etan marks, do1, hillary g. caruso, phd2, sarah j. kurley, phd2, sidra ibad, md3, kristen m. plasseraud, phd2, federico a. monzon, md, fcap2, clay j. cockerell, md4 1ut southwestern medical center, dallas, tx 2castle biosciences, inc., friendswood, tx 3icahn school of medicine at mount sinai, new york, ny 4cockerell dermatopathology, dallas, tx the observation that two-thirds of stage i-iii melanoma deaths occur in patients who have no evidence of distant metastatic spread at diagnosis (stage i-ii) suggests that improved prognosis of metastatic risk prognosis is necessary.1 to address this clinical need, a 31-gene expression profile (31-gep) test was developed and validated, providing prognostic information based on the biology of the primary melanoma tumor.2-5 numerous retrospective and prospective studies have demonstrated that the 31-gep is a significant and independent predictor of survival, beyond traditional clinicopathologic staging factors and sln status.3,4, 6-9 recognizing the introduction treatment plans for cutaneous melanoma are based upon individual risk of recurrence. decisions made post-diagnosis include recommendation for a sentinel lymph node biopsy (slnb), followed by management decisions such as surveillance, frequency of follow-up, and interdisciplinary consultations including possible adjuvant therapy use. these have traditionally been guided by clinicopathologic factors, but discordance exists, as a substantial number of melanoma deaths occur in patients diagnosed with disease considered to be early stage by such factors, including a negative slnb. molecular testing can be used to apply an objective approach that optimizes individualized patient care. the 31-gene expression profile (31-gep) test has been validated in nearly 1600 patients as an independent predictor of risk of recurrence, distant metastasis and death in stage i-iii melanoma and can guide slnb decisions in patient subgroups, as demonstrated in 1421 patients. while clinical use of the 31gep test has been adopted into routine practice, an evidence-based analysis of a decision point for use in thin, t1 tumors would be clinically useful. to help define an appropriate population for 31-gep testing, we evaluated changes in patient management, cumulative differential risk across breslow thicknesses based on a large dataset, and 31-gep subclass distribution in a clinically tested cohort. based on this, appropriate use of the 31-gep test for management decisions was found to be in cutaneous melanoma tumors ≥0.3 mm thick. abstract skin july 2019 volume 3 issue 4 copyright 2019 the national society for cutaneous medicine 240 clinical value of the 31-gep, physicians have utilized it to inform decisions of intensity of follow-up, including use and frequency of clinical visits, labs, imaging, and referrals.1012 patients are classified by the 31-gep test as low-risk (class 1, 1a lowest risk) or high-risk (class 2, 2b highest risk) based on differential expression of a panel of 28 discriminating gene targets and 3 control genes.2,5,13 previous studies have reported that the 31-gep identifies high-risk disease in traditionally low-risk subsets of patients, including those with thin (≤1.0 mm, t1) tumors.3,4,14 this finding allows for the appropriate identification of patients for escalation and de-escalation of interventions. as adoption of the 31-gep test increases, the natural question arises: what patient population is appropriate for 31-gep testing? this is a particularly important question for patients with thin melanomas traditionally associated with good outcomes, having a 5year melanoma-specific survival of 9699%.15, 16 a non-invasive prognostic tool such as the 31-gep can be useful to identify those t1 tumors with increased risk of metastasis and death from melanoma, but the threshold at which the test is expected to have true clinical value has not yet been reported. in this study, we define a target population for 31-gep clinical use by i) estimating 5-year recurrence-free (rfs) and distant metastasis-free survival (dmfs) rates associated with t1 tumors and cumulative event rates in t1-t2 tumors using a large multi-center dataset; ii) reviewing 31-gep clinical reports to evaluate the frequency of when high-risk, class 2 biology is detected in clinically tested patients with t1 tumors; and iii) analyzing data from previously published clinical utility studies to determine the tumor thickness threshold at which patient management decisions were changed based on the results of the 31-gep test. the goal of the study is to suggest a more targeted application of the 31-gep test for patients with thin tumors that can improve resource management and health care outcomes, and to summarize appropriate use relative to the two validated utilities of the 31-gep test in the context of current melanoma management strategies. clinical outcomes study cohorts and data collection 31-gep test results, tumor clinicopathologic data, and clinical outcomes were derived from three non-overlapping published study cohorts, including prospectively-tested patients6, 7 and archival tumor specimens3, as well as an independent archival tumor cohort (total n=1479).17 median follow-up for the patients in the combined cohort was 3.3 years. all tumor specimens and associated clinical data were collected under institutional (irb)-approved protocols or were deemed exempt by the irb. cumulative event analysis by breslow thickness total number of cases and recurrence events (events documented as being locoregional or distant recurrences) from the 1479 patients described above were analyzed according to breslow thickness and 31-gep class using r.3.6. for tumors between 0.0-2.0 mm breslow thickness (n=1037) cumulative event rates at each observed case within the 31-gep subclasses were calculated and plotted. loess regression was used to fit a smoothed curve to these plotted points. breslow thickness binning in all analyses was methods skin july 2019 volume 3 issue 4 copyright 2019 the national society for cutaneous medicine 241 used as per ajcc v8 guidelines (i.e. rounding to nearest tenth of a mm)16. clinical gep testing data de-identified consecutive 31-gep clinical test results and associated tumor clinicopathologic data (n=579) between 2014 and 2019 from a large dermatopathology practice were used to determine proportions of 31-gep classes in t1 melanoma tumors by 0.1 mm increments in breslow thickness. de-identified 31-gep clinical test results and associated tumor clinicopathologic data between may 2018 to april 2019 were also used to determine proportions of 31-gep classes in t1 tumors by 0.1 mm increments in breslow thickness. analysis of clinical utility according to breslow thickness raw data from two published, multi-center clinical impact studies10, 11 (n=403) were used to analyze management changes (including changes in referrals, clinical visits, imaging, laboratory tests, and slnb recommendations) in consecutively tested patients that were made following 31-gep test result receipt, according to breslow thickness. all clinicopathologic data, 31-gep test results, and clinical use data were collected under irb-approved protocols. outcomes in the t1 population according to breslow thickness and 31-gep class to estimate differences in risks associated with the 31-gep test results at any given breslow thickness in t1-t2 tumors, outcomes and clinicopathologic data from 1479 patients with a median follow-up of 3.3 years were used. cumulative recurrence rates (cumulative recurrences/cumulative cases) in 31-gep subclasses were calculated at each observed case and plotted. patient and pathologic characteristics of tumors ≤2.0 mm (n=1037) are shown in table 1. a smoothed curve was fit using loess regression to show the estimated cumulative event rate (cumulative recurrences/total cases in 31-gep subclass) at each observable breslow thickness. as shown in figure 1, the predicted cumulative rates of recurrence from the loess curve for class 2b separates from the class 1a tumors between 0.2 and 0.3 mm breslow thickness. importantly, the first recurrent/distant metastatic event occurred in a 0.3 mm tumor and thus 5-year rfs and dmfs survival rates are 100% for tumors ≤0.2 mm and significantly different with 31-gep class in patients with tumors 0.3-1.0 mm thick by logrank test (p<0.0001 for rfs; p=0.0008 for dmfs) (table 2). in patients with tumors 0.31.0 mm thick, class 2b results were associated with rfs and dmfs rates of 75.5% and 82.1%, respectively, compared to rates of 96.8% and 97.4% for class 1a. as these data suggested a potential target threshold for clinical utility, the threshold of 0.3 mm was explored in the next set of analyses. frequency of 31-gep subclasses in thin melanomas to determine the prevalence of 31-gep subclasses in thin melanomas, de-identified test results and clinicopathologic data from a large dermatopathology practice were evaluated for 31-gep subclass and breslow thickness (n=437 with breslow thickness ≤1.0 mm and a 31-gep subclassification) (figure 2a). additionally, de-identified 31-gep results and clinicopathologic data from tumors 0.1-1.0 mm clinically tested between may 2018 and april 2019 (n=8944) were results skin july 2019 volume 3 issue 4 copyright 2019 the national society for cutaneous medicine 242 evaluated (figure 2b). in the dermatopathology practice, tumors <0.3 mm breslow thickness were exclusively class 1a, while class 1b, 2a, and 2b results were obtained for tumors ≥0.3 mm breslow thickness such that 7.1% of tumors ≥0.3 mm and ≤1.0 mm had class 2 results and 15.7% of tumors ≥0.3 mm had non-class 1a (e.g. class 1b, 2a or 2b) results (figure 2a). in the overall clinically tested population from the last year, tumors <0.3 mm were primarily class 1a, with few class 1b, 2a, and 2b tumors. however, 4.3% of tumors ≥0.3 mm were class 2 and 10.8% were non-class 1a (figure 2b). physicians’ use of 31-gep test to change management decisions and relationship to breslow thickness in thin tumors four clinical impact studies have shown that the 31-gep test is associated with a ~50% rate of management changes when incorporated with available clinicopathologic staging.10-12, 18 of these, two are multi-center studies of consecutively tested patients that demonstrated changes in clinical visits, slnb recommendations, frequency and intensity of surveillance imaging, laboratory testing and specialty referrals.10, 11 those two studies included a total of 403 patients, of which 160 had primary melanomas ≤1.0 mm thick. to evaluate the impact of 31-gep on patient management at various breslow thicknesses, t1 melanomas were categorized by reported breslow thickness by 0.1 mm increments, and it was determined if a change in management was recommended post-testing. as shown in figure 3, most of the management changes for thin (t1) melanomas following receipt of the 31-gep test were recommended for lesions with ≥0.3 mm breslow thickness. specifically, 25% of the lesions between 0.3 mm and 1.0 mm had a management change, while 11% of lesions <0.3 mm had a recommended management change. figure 1. outcomes associated with 31-gep subclasses across breslow depths in t1-t2 tumors. data from a multi-center cohort of 1479 tumors were used to calculate cumulative recurrence rates (cumulative events/cumulative cases in each 31gep subclass) at each observed t1-t2 tumor in the dataset. loess regression was used to fit a smooth curve to the points and estimate cumulative recurrence rates across breslow thicknesses between 0.0 and 2.0 mm. skin july 2019 volume 3 issue 4 copyright 2019 the national society for cutaneous medicine 243 figure 2. 31-gep subclass distribution with breslow thickness in large clinically tested cohorts. a) t1 tumors clinically tested with the 31-gep test between 2014 to 2019 at a large dermatopathology practice were evaluated for 31-gep result (n=479). b) t1 tumors clinically tested with the 31-gep test between may 2018 and april 2019 (n=8944). percent of tumors in each 31-gep subclass were plotted according to 0.1 mm breslow thickness increments. in both panels, non-class 1a results are shown. skin july 2019 volume 3 issue 4 copyright 2019 the national society for cutaneous medicine 244 figure 3. management changes in 31-gep-tested t1 tumors by 0.1 mm breslow thickness increments. management changes (change in frequency of clinical visits, imaging, referrals, sentinel lymph node biopsy, laboratory tests) after receipt of 31-gep test results associated with t1 tumors (n=160) from two published studies10, 11 were compiled and evaluated by 0.1 mm increments in tumor breslow thickness. blue bars indicate no change in management and red bars indicate a management change (increase or decrease in intensity). table 1. patient and tumor characteristics of t1-t2 cohort. feature class 1a (n=718) class 1b (n=126) class 2a (n=88) class 2b (n=105) combined (n=1037) age (years), p<0.001 mean and sd 58.4 (±15.8) 57.8 (±13.5) 61.2 (±14.5) 64.5 (±15.1) 59.2 (±15.4) median (range) 60 (18-91) 57.5 (26-87) 61 (19-88) 67 (20-93) 60 (18-93) breslow depth (mm), p<0.0001 mean and sd 0.7 (±0.431) 1.1 (±0.436) 1.3 (±0.52) 1.3 (±0.464) 0.9 (±0.495) median (range) 0.6 (0.1-2.0) 1.0 (0.2-2.0) 1.3 (0.2-2) 1.3 (0.1-2) 0.8 (0.1-2) ulceration, p<0.0001 no 605 / 718 (84.26%) 93 / 126 (73.81%) 61 / 88 (69.32%) 50 / 105 (47.62%) 809 / 1037 (78.01%) unknown 75 / 718 (10.45%) 11 / 126 (8.73%) 10 / 88 (11.36%) 5 / 105 (4.76%) 101 / 1037 (9.74%) yes 38 / 718 (5.29%) 22 / 126 (17.46%) 17 / 88 (19.32%) 50 / 105 (47.62%) 127 / 1037 (12.25%) skin july 2019 volume 3 issue 4 copyright 2019 the national society for cutaneous medicine 245 table 2. 5-year outcomes of patients with t1 tumors above and below 0.3mm. group 31-gep class n rfs (95% ci) p-value dmfs (95% ci) p-value ≤0.2 mm all 56 100% (100-100%) n/a 100% (100-100%) n/a 0.3-1.0 mm class 1a 495 96.76% (94.73-98.83%) p<0.0001 97.35% (95.39-99.34%) p=0.0008 class 1b 62 91.01% (82.97-99.82%) 90.58% (82.21-99.81%) class 2a 24 90.91% (79.66-100%) 90% (77.77-100%) class 2b 32 75.46% (60.95-93.42%) 82.14% (67.51-99.95%) 31-gep: 31-gene expression profile; rfs: recurrence-free survival; dmfs: distant metastasis-free survival skin july 2019 volume 3 issue 4 copyright 2019 the national society for cutaneous medicine 246 while the risk of mortality is strongly correlated with breslow thickness, a substantial proportion of melanoma-specific deaths occur in patients initially diagnosed with thin, t1 melanomas,15, 19-21 because of the relative prevalence of t1 to thick melanomas (t4, breslow depth >4 mm). thus, patients with thin melanoma represent the majority of cutaneous melanoma patients and a subset of these patients have poor outcomes, which accounts for a significant percentage of melanoma-related deaths. the 31-gep test was developed and validated to enhance prognostic accuracy in melanoma,2 and its overall performance, as well as the performance in thin melanomas, has been previously reported.3-9, 17 with any clinical test, it is important to identify a population for whom use of the test is appropriate and has the potential to add value to patient care. this study was aimed at defining an evidence-based target population of tumors for which 31-gep testing can maximize sensitivity of identifying class 2 results and where the test result is more likely to result in a clinically appropriate and meaningful change in an individual patient’s treatment plan. to do so, we used a combination of outcomes, 31-gep class frequency and clinical utility to identify a breslow thickness threshold at and above which the 31-gep test can be used to estimate differential risk of recurrence and inform management decisions based on that predicted risk. we used a large dataset of patient tumors and clinical outcomes (i.e. recurrence and distant metastatic events) to estimate 5-year rfs and dmfs rates, as well as cumulative event rates at any given breslow thickness ≤1.0 mm, and found that there was an observable shift in predicted cumulative event rates above 0.3 mm between class 1a and class 2b tumors, which have the lowest and highest risks of recurrence, respectively. of note, estimated cumulative event rates are based on loess regression fitting to cumulative event rates at each observed case per 31-gep subclass in the patient cohort. since the cumulative event rate at each observed case in the data set reflects that case and those with lower breslow thicknesses, the cumulative event rates derived from the loess curve may underestimate the risk of recurrence at a given local breslow thickness. additionally, there are fewer recurrence events, as expected, in ultra-thin melanomas and this must be considered when interpreting the fitted curves. thus, the importance of this analysis is the separation of cumulative rates of recurrence between class 1a and 2b at the 0.3 mm threshold. we then evaluated 31-gep class distribution in thin melanoma tumors from a large dermatopathology practice and in all cases clinically tested during the last year. in patients with tumors 0.3 mm to 1.0 mm from the dermatopathology practice, a 7.1% frequency of class 2 tumors and a 15.7% frequency of non-class 1a tumors were identified. distribution of class results will likely vary practice to practice based on different patient population. figure 2b shows the distribution across 8944 t1 tumors clinically tested during a one-year period. in this population, very few tumors <0.3 mm were classified as non-class 1a, indicating a large number of patients would need to be tested in order to identify a high-risk tumor. in tumors 0.3-1.0 mm, 10.8% were non-class 1a, suggesting a benefit of risk assessment for this portion of the thin tumor population. lastly, we identified that most changes in patient management for consecutively tested discussion skin july 2019 volume 3 issue 4 copyright 2019 the national society for cutaneous medicine 247 melanomas after 31-gep testing were made for tumors ≥0.3 mm in breslow thickness. taken together, results from these three sets of analyses point towards use of the 31-gep test to guide management decisions for patients with tumors ≥0.3 mm thick for risk of recurrence prediction. below 0.3 mm in thickness, there are no observed recurrence events in our research patient cohort, suggesting a very low frequency of recurrence/metastasis in this group, and there are very few expected non-class 1a results. moreover, physicians have not shown strong impact of test results to change patient management. in summary, these results suggest a breslow thickness threshold of 0.3 mm for using the 31-gep test for guiding management decisions dependent on individual risk of recurrence. in the context of the comprehensive use of the 31-gep test, the test is also used to guide decisions on using slnb in patients with t1-t2 tumors, as reported recently22. since the slnb surgical procedure is currently recommended by nccn guidelines for t1a tumors with adverse features, there is a population of patients with <0.3 mm tumors with adverse features who could still be considered for this procedure, and in this population there is utility of the 31-gep test in identifying patients at very low risk of being slnb positive who can avoid this procedure. the schematic in figure 4 depicts both ways the test informs management decisions for melanoma patients and recommended thresholds based on published literature and the analysis presented herein. figure 4. appropriate use and target populations for 31-gep test to guide sentinel lymph node biopsy (slnb) decisions and patient management. based on published studies and current study data, the 31-gep test is recommended to be used in patients with t1-t2 tumors (including <0.3 mm tumors with adverse features) for slnb decision guidance (left) and in tumors with ≥0.3 mm breslow thickness for risk of recurrence prediction to inform patient management decisions (right). skin july 2019 volume 3 issue 4 copyright 2019 the national society for cutaneous medicine 248 conflict of interest disclosures: cjc has served as a consultant and speaker for castle biosciences, inc. hgc, sjk, kmp, and fam are employees and options holders at castle biosciences, inc. em and si have no conflicts of interest to declare. funding: none. corresponding author: etan marks, do ut southwestern medical center dallas, tx etanmarks@gmail.com references: 1. morton dl, thompson jf, cochran aj, et al. final trial report of sentinel-node biopsy versus nodal observation in melanoma. n engl j med. 2014;370: 599-609. 2. gerami p, cook rw, wilkinson j, et al. development of a prognostic genetic signature to predict the metastatic risk associated with cutaneous melanoma. clin cancer res. 2015;21: 175-183. 3. gastman br, gerami p, kurley sj, cook rw, leachman s, vetto jt. identification of patients at risk of metastasis using a prognostic 31-gene expression profile in subpopulations of melanoma patients with favorable outcomes by standard criteria. j am acad dermatol. 2019;80: 149-157.e4. 4. zager js, gastman br, leachman s, et al. performance of a prognostic 31-gene expression profile in an independent cohort of 523 cutaneous melanoma patients. bmc cancer. 2018;18: 130. 5. gerami p, cook rw, russell mc, et al. gene expression profiling for molecular staging of cutaneous melanoma in patients undergoing sentinel lymph node biopsy. j am acad dermatol. 2015;72: 780-785.e3. 6. greenhaw bn, zitelli ja, brodland dg. estimation of prognosis in invasive cutaneous melanoma: an independent study of the accuracy of a gene expression profile test. dermatol surg. 2018;44: 1494-1500. 7. hsueh ec, debloom jr, lee j, et al. interim analysis of survival in a prospective, multi-center registry cohort of cutaneous melanoma tested with a prognostic 31-gene expression profile test. j hematol oncol. 2017;10: 152. 8. keller j, schwartz tl, lizalek jm, et al. prospective validation of the prognostic 31-gene expression profiling test in primary cutaneous melanoma. cancer med. 2019. 9. podlipnik s, carrera c, boada a, et al. early outcome of a 31-gene expression profile test in 86 ajcc stage ib-ii melanoma patients. a prospective multicentre cohort study. j eur acad dermatol venereol. 2019. 10. berger ac, davidson rs, poitras jk, et al. clinical impact of a 31-gene expression profile test for cutaneous melanoma in 156 prospectively and consecutively tested patients. curr med res opin. 2016;32: 1599-1604. 11. dillon ld, gadzia je, davidson rs, et al. prospective, multicenter clinical impact evaluation of a 31-gene expression profile test for management of melanoma patients. skin. 2018;2: 111121. 12. schuitevoerder d, heath m, cook rw, et al. impact of gene expression profiling on decision-making in clinically node negative melanoma patients after surgical staging. j drugs dermatol. 2018;17: 196-199. 13. cook rw, middlebrook b, wilkinson j, et al. analytic validity of decisiondx melanoma, a gene expression profile test for determining metastatic risk in mailto:etanmarks@gmail.com skin july 2019 volume 3 issue 4 copyright 2019 the national society for cutaneous medicine 249 melanoma patients. diagn pathol. 2018;13: 13. 14. ferris lk, farberg as, middlebrook b, et al. identification of high-risk cutaneous melanoma tumors is improved when combining the online american joint committee on cancer individualized melanoma patient outcome prediction tool with a 31-gene expression profilebased classification. j am acad dermatol. 2017;76: 818-825.e3. 15. shaikh wr, dusza sw, weinstock ma, oliveria sa, geller ac, halpern ac. melanoma thickness and survival trends in the united states, 1989 to 2009. j natl cancer inst. 2016;108. 16. gershenwald je, scolyer ra, hess kr, et al. melanoma staging: evidence-based changes in the american joint committee on cancer eighth edition cancer staging manual. ca cancer j clin. 2017;67: 472-492. 17. greenhaw bn, hsueh ec, covington kr, plasseraud km, cook rw, gastman br. meta-analysis of the prognostic 31gene expression profile test in 1261 cutaneous melanoma cases. american academy of dermatology. washington, d. c. , 2019. 18. farberg as, glazer am, white r, rigel ds. impact of a 31-gene expression profiling test for cutaneous melanoma on dermatologists' clinical management decisions. j drugs dermatol. 2017;16: 428-431. 19. gimotty pa, elder de, fraker dl, et al. identification of high-risk patients among those diagnosed with thin cutaneous melanomas. j clin oncol. 2007;25: 1129-1134. 20. landow sm, gjelsvik a, weinstock ma. mortality burden and prognosis of thin melanomas overall and by subcategory of thickness, seer registry data, 19922013. j am acad dermatol. 2017;76: 258-263. 21. whiteman dc, baade pd, olsen cm. more people die from thin melanomas (1 mm) than from thick melanomas (>4 mm) in queensland, australia. j invest dermatol. 2015;135: 1190-1193. 22. vetto jt, hsueh ec, gastman br, et al. guidance of sentinel lymph node biopsy 316 decisions in patients with t1-t2 melanoma using gene expression profiling. future oncol. 2019;15: 12071217. skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 234 brief article a case of cutaneous metastatic tonsillar squamous cell carcinoma in a female haley d. heibel, md1, chris bandel, bs2, claire reddick, md3, and clay j. cockerell, md, mba2, 4 1 department of dermatology, northwestern university feinberg school of medicine, chicago, il 2 cockerell dermatopathology, dallas, tx 3 austin reddick dermatology, dallas, tx 4 departments of dermatology and pathology, ut southwestern medical center, dallas, tx cutaneous metastases in patients with squamous cell carcinoma (scc) of the head and neck are rare and develop in 1-2.4% of these cases.1 tonsillar scc is a minority of head and neck cancers, making up approximately 10% of cases.2,3 to our knowledge, only 8 cases of cutaneous metastatic tonsillar scc previously have been reported in the english literature.1-7 here, we present the third case of a female with cutaneous metastatic tonsillar scc.3,6 a 46-year-old female presented to the dermatology clinic with a mass on her left lateral neck. she had a past medical history of tonsillar scc of her left neck, which was hpv 16 positive, that was diagnosed and surgically excised with clear margins approximately two years previously. she additionally received radiation therapy to the left neck after surgery. she had associated lymphadenopathy at the time of diagnosis that gradually resolved. she was in remission and subsequently developed a small, nontender mobile nodule on her left neck approximately one and a half years after the diagnosis of her tonsillar scc. over the next six months, the lesion increased in size. the lesion ulcerated and also started leaking clear, yellow fluid that became cloudy over time within two months of being noticed by the patient. physical examination revealed a firm violaceous plaque with ulceration on the patient’s left lateral neck (fig. 1). abstract cutaneous metastatic tonsillar squamous cell carcinoma (scc) is extremely rare and carries a poor prognosis. to our knowledge, only 8 cases of cutaneous metastatic tonsillar scc previously have been reported in the english literature. here, we present the third case of a female with cutaneous metastatic tonsillar scc. introduction case report skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 235 figure 1. cutaneous metastatic tonsillar scc. physical examination demonstrated a firm, nonfluctuant violaceous nodule that was 9 by 3.5 cm with ulceration (with approximately a 2.5 cm diameter) on the patient’s left lateral neck. histopathological examination demonstrated deep, focal areas of squamous differentiation that were not contiguous with the epidermis (fig. 2). figure 2. cutaneous metastatic tonsillar scc (h&e). histopathological examination demonstrated deep, focal areas of squamous differentiation with a distinct basaloid morphology that were not contiguous with epidermis. there was no contiguity with the underlying tonsillar tissue that had been completely excised two years previously. there was no contiguity with the underlying tonsillar tissue that had been completely excised two years previously. the cells had a distinct basaloid morphology suggestive of either neuroendocrine carcinoma or possibly a metastasis of the patient’s known tonsillar scc. immunohistochemical staining for cytokeratin was positive (fig. 3), and stains for cytokeratin-20 and insm-1 were negative, ruling out neuroendocrine carcinoma and favoring a basaloid scc, likely a metastasis from the patient’s tonsillar scc. figure 3. cutaneous metastatic tonsillar scc (cytokeratin). immunohistochemical staining for cytokeratin was positive, consistent with a diagnosis of basaloid scc from the primary tonsillar scc that metastasized to the skin. staining for p16 was negative. the slides from the needle biopsy of the patient’s primary tumor were obtained and also showed a basaloid morphology in addition to the squamous morphology, confirming the skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 236 diagnosis of metastatic tonsillar scc. the patient was referred to surgical oncology for further management. cutaneous metastatic tonsillar scc is extremely rare and carries a poor prognosis.2,4,8 in a retrospective review by yoskovitch et al,8 the average survival time for patients with skin metastases in scc of the head and neck was 7.2 months. risk factors for tonsillar carcinoma include alcohol, smoking, and human papillomavirus (hpv) infection.1,2,8 basaloid scc tends to metastasize, and 6 of the 8 reported cases of metastatic tonsillar scc have occurred in males.1,2,4-7 the clinical presentation of cutaneous metastatic tonsillar scc varies widely and may be the first evidence of recurrent malignancy.1,8 clinical presentations have included erythematous patches, papules, plaques, nodules, and swelling of the scalp.1,3 the surface of these lesions may be intact or ulcerated.3 a previously reported case of a female with cutaneous metastatic tonsillar scc presented with an erythematous and indurated plaque of the left eyelid, with a monocle clinical pattern, which resolved after chemotherapy.3 in cases of scc of the head and neck that are recurrent or metastatic, hpv positivity is a favorable prognostic factor.1 radiation, chemotherapy, and surgery are palliative treatment options.1,6 one patient had resolution of her skin metastasis with combined therapy of cetuximab, carboplatin, and fluorouracil.3 another case described clinical resolution of cutaneous lesions, which demonstrated high expression of pdl1, and improvement on imaging (positron emission tomography/computed tomography) of metastatic lymph nodes with nivolumab therapy.1 with the small number of reported cases of cutaneous metastatic tonsillar scc, information regarding optimal treatment of patients is limited, although hpv testing may be useful to guide treatment decisions.1 abbreviations used: human papillomavirus (hpv), squamous cell carcinoma (scc) conflict of interest disclosures: none funding: none prior presentations: this case was presented at the zola cooper – lee t. nesbitt clinical and dermatopathologic seminar; november 14, 2020; virtual platform, the inaugural skin cancer symposium; april 7-8, 2021; virtual platform, and the 2021 annual spring texas dermatological society meeting; april 30-may 1, 2021; virtual platform. corresponding author: haley d. heibel, md 875 n. michigan avenue suite 1525 chicago, il 60611 phone: (312) 227-6817 fax: (312) 227-9402 email: haley.heibel@northwestern.edu references: 1. ramser ae, craig em, delost gr, baron e. cutaneous metastasis of tonsillar carcinoma: report of a rare case. jaad case reports. 2018;4(6):551-554. 2. bari o, cohen pr. cutaneous metastasis from tonsillar squamous cell carcinoma: report and review of the literature. cureus. 2017;9(3):e1122. 3. lobato‐berezo a, fernández‐figueras mt, campoy a, pujol rm, moya‐horno i. monocle tumor as tonsillar squamous cell carcinoma metastasis: resolution after chemotherapy treatment. int j dermatol. 2018;57(4):498-500. 4. chikkannaiah p, boovalli mm, kumar rp, murthy vs. unusual cases of carcinoma of palatine tonsil. j oral maxillofac pathol. 2015;19(2):242-246. discussion conclusion skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 237 5. dasmajumdar sk, gairola m, sharma dn, mohanti bk. cutaneous metastasis from carcinoma of tonsil. j postgrad med. 2002;48(1):32-33. 6. poovaneswaran s, paleri v, charlton f, dobrowsky w, kelly c. cutaneous metastases from head and neck squamous cell carcinoma. med j malaysia. 2012;67(4):430-432. 7. singh gk, yadav v, singh p, bhowmik kt. multiple cutaneous metastases in a patient of carcinoma tonsil – report of a rare case. j egypt natl canc inst. 2016;28(3):191-193. 8. yoskovitch a, hier mp, okrainec a, black mj, rochon l. skin metastases in squamous cell carcinoma of the head and neck. otolaryngol head neck surg. 2001;124(3):248-252. skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 155 rising derm stars® the use of doxycycline in lichen planopilaris and frontal fibrosing alopecia: a retrospective study of 138 patients at a tertiary referral clinic janice tiao, md1, lynne j. goldberg, md 1department of dermatology, boston university medical center, boston, ma, usa background/objectives: lichen planopilaris (lpp) and frontal fibrosing alopecia (ffa) are lymphocyte-mediated primary cicatricial alopecias (1). they are rare, and limited evidence exists on treatment options (1-2). the best data supports hydroxychloroquine as the first-line systemic therapeutic agent (1,3), although expert opinion cites doxycycline as an acceptable first-line alternative and small series support its potential efficacy (4-5). the purpose of this study is to describe the use of doxycycline in patients with lpp and ffa at a single tertiary referral clinic. methods: after obtaining irb approval, the authors reviewed the medical records of 138 patients with lpp and ffa who presented to the outpatient specialty hair clinic at boston university medical center from 2015-2017. results: of 138 subjects, 1 was excluded because there was no electronic medical record on file. thirty-one subjects had a diagnosis of lpp, 103 had a diagnosis of ffa, and 3 were diagnosed with both lpp and ffa. of the 31 lpp-only subjects, 16 had been prescribed doxycycline for their condition. of these subjects, 9 (56.3%) reported or were observed to improve or stabilize, 2 (12.5%) did not improve, and 5 (31.3%) had unclear response or were lost to follow up. of the 106 subjects with ffa, 40 had been prescribed doxycycline for their condition. of these 40 subjects, 17 (42.5%) were felt to improve or stabilize, 7 (17.5%) did not improve, and 15 (37.5%) had unclear response or were lost to follow up. the average duration of use was 8 months. of note, 14 of 56 (25%) subjects who took doxycycline discontinued the medication secondary to side effects, most commonly gastrointestinal. conclusion: although a number of subjects did not tolerate the medication, the data confirm that doxycycline may be helpful in the treatment of lpp and ffa. references: 1. bolduc, c., sperling, l.c., shapiro, j. primary cicatricial alopecia. j am acad dermatol 2016;75:1081-99. 2. ochoa, b.e., king, l.e., price, v.h. lichen planopilaris: annual incidence in four hair referral centers in the united states. j am acad dermatol 2008;58:352-3. 3. errichetti, e., figini, m., croatto, m., stinco, g. therapeutic management of classic lichen planopilaris: a systematic review. clin cosmet investig dermatol 2018;11:91-102. skin march 2019 volume 3 issue 2 copyright 2018 the national society for cutaneous medicine 156 4. spencer, l.a., hawryluk, e.b., english, j.c. lichen planopilaris: retrospective study and stepwise therapeutic approach. arch dermatol 2009;45:3334. 5. lyakhovitsky, a., amichai, b., sizopoulou, c., barzilai, a. a case series of 46 patients with lichen planopilaris: demographics, clinical evaluation, and treatment experience. j dermatolog treat 2015;26:275–9. improving dermatology resident billing ucb resident poster competition.pptx . . . . . . . . . . improving dermatology resident billing michael tassavor, md, shayan owji, bs, joseph han, bs, cula dautriche, md, jonathan ungar, md department of dermatology, icahn school of medicine at mount sinai methods • all cpt codes and modifiers were recorded for approximately 256 patient encounters before and after our intervention. • the intervention consisted of four monthly billing lectures with two associated quizzes as well as a note template designed by author mt that automatically lists the correct procedural codes according to the numbers and types of procedures chosen from a dropdown list • billing accuracy was verified by two attending dermatologists through chart review and compared between the two time periods • state population and setting conclusions • lectures on medical coding and a template that automatically lists the cpt codes for procedures greatly improved the billing accuracy of dermatology residents at our institution, significantly decreasing the rate of errors for procedural codes and modifiers • residents consistently undercoded e/m rather than the opposite, perhaps due to a perception that there is no meaningful benefit to maximizing their billing • our lectures seemed to be most impactful on procedural codes and modifiers results • billing data from 513 patient visits, 257 from the pre-intervention period and 256 from the post-intervention period, were checked for accuracy • the accuracy of resident-billed e/m levels of service was similar between preand post-intervention (44.4% vs. 44.8%) • similar rates of undercoding and overcoding were noted between the preand post-intervention periods (35.4% undercoded and 8.1% overcoded vs. 35.8% and 8.9%). • substantial improvements were noted in the rate of errors with procedural codes and modifiers in the post-intervention period • 22.0% of procedural codes were incorrectly billed pre-intervention while only 3.7% were incorrectly billed post-intervention (p<0.05). • 55.2% of modifiers were incorrectly billed pre-intervention while only 27.3% were incorrectly billed post-intervention (p<0.05). synopsis • resident billing performance can have significant financial implications for the academic institutions employing them • to assess the impact of newly implemented medical coding lectures and a modified note template on resident billing accuracy, resident billing accuracy from the preand postintervention periods were compared • billing lectures and a modified note template yielded a clear improvement on resident billing accuracy at our institution figure 1: breakdown of the percentage of undercoded and overcoded e/m codes in the preand post-intervention periods. figure 2: percentage of total procedural codes and modifiers that were incorrectly billed in the preand post-intervention periods. cryosurgery: number of lesions treated: *** location of lesions treated: *** procedure: liquid nitrogen applied to lesion(s) for *** seconds, for *** freeze-thaw cycles. complications: none. cpt codes: premalignant: 17000 for 1, also add 17003 for 2-14 (units = number of lesions). 17004 used alone for 15+ (units = 1). benign: 17110 for 1-14, 17111 for 15+ (units = 1 for both) figure 3: screenshot of the note template addition that lists the correct codes for each procedure skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 177 short communication surprise medical billing reform: considerations for dermatology yuangao liu, bs1, natalie c. skopicki, harrison p. nguyen, md, mba, mph, dtm&h2, travis w. blalock, md2 1 school of medicine, baylor college of medicine, houston, tx 2 department of dermatology, emory university school of medicine, atlanta, ga surprise billing occurs when patients with health insurance receive care from a clinician or facility included in their insurer’s network (“in-network”) but unexpectedly receive “surprise” bills from other clinicians involved in their care who are not in the their insurer’s network (“out-of-network”).1 since insurance plans are not required to reimburse out-of-network providers their full charges, those out-of-network clinicians or facilities may bill the patient for the difference between the payment and their charges. patients are liable for these unexpected charges (“balance bills”), which may be substantial and financially burdensome. in dermatology, surprise medical billing may manifest through consultation (i.e., in the emergency room or inpatient setting) or via dermatopathology services. reforming surprise billing is not straightforward since solutions must consider patient protection, physician autonomy, and free market dynamics. as of 2021, 33 states have enacted laws to protect patients from surprise billing, but the scope of these protections varies (figure 1). 2 comprehensiveness of protections varies based on setting (emergency department vs. non-emergent care), type of insurance plan (i.e., health maintenance organization (hmo) or preferred provider organization (ppo)), extent of protections, and presence of dispute resolution processes. for example, texas has comprehensive protection that prohibits out-of-network providers from billing hmo and ppo enrollees for any amount beyond in-network cost sharing in both emergent and nonemergent settings, except enrollees who electively consent to out-of-network nonemergency services. in contrast, pennsylvania has partial protection covering emergency department services but does not have a dispute resolution process for payments.2 the no surprises act is a federal bill with the stated intent of reforming surprise medical billing and was signed into law in december 2020 as part of the consolidated appropriation act of 2021.3 most of the legislation went in effect on january 1st, 2022 (table 1). the no surprises act seeks to set national standards to protect patients from unexpected medical bills while establishing processes for providers and payers to resolve billing disputes. arbitrators of billing disputes will be prohibited from considering charges and will instead rely on median in-network rates for services. furthermore, arbitrators will be required to consider case-specific nuances, skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 178 figure 1. states’ balance-bill protections as of 20212 table 1. brief overview of relevant sections in the no surprises act.3 sect. regulations considerations 102 cost sharing determination • patient cost-sharing limits for out-of-network services are based on a “recognized amount” and a “qualifying amount.” • set based on the median contract rate recognized by the health plan on jan 31, 2019 within the same insurance market in the same geographic region. • protects patients from substantial billing from out-of-network providers. • diminishes incentive for insurers to expand their networks since anyone outside of the network is being paid at the median rate. • arbitrators can consider a wide range of factors but not the provider’s usual and customary charges. 103 independent dispute resolution process (idr) • 30-day open negotiation period between provider and health plan to come to an agreement on reimbursement. • either party may trigger the idr process if no agreement is reached after the initial 30 days. • the party that submits the losing bid is responsible for the costs of idr process. • the idr process protects patients from being in the middle of payment rate negotiations between providers and insurers. • it may take 60 days for physicians to seek fair compensation and costs involved in idr process may put small dermatology practices under significant financial strain. 104 an out-of-network provider may submit balance bills if they satisfy the notice and consent process. • notification that the provider is out-of-network. • good faith estimates of the charges. • a list of in-network providers at the facility to which the patient can be referred. • information on prior authorization or other care management requirements. • providers may not know in advance who will be involved in an episode of care and other providers’ contract status. • uncertainties in the practicality of maintaining an accurate up-todate provider directory, and inaccuracy in the directory can lead to confusion for patients and providers. • time spent on consent process may limit the time available for patient care. 112 requirement for providers and facilities to share “good faith estimates” of the total expected charges for scheduled items or services. • determine the estimate at least 3 business days before service date or no later than 1 business day after scheduling (if the service is scheduled more than 10 business days later, then no later than 3 business days after scheduling). • establishes a patient-provider dispute resolution process for uninsured patients who receive a bill $400 higher than the “good faith estimate.” • improved patient protections via price transparency have the potential to alter the patient-provider relationship by adding in financial factors. • provider may not be able to predict complications, other indicated procedures, or undiscovered diagnosis prior to a procedure for a “good faith estimate”, which may induce mistrust and frustration for both providers and patients. • the patient-provider dispute resolution process may put additional strain onto the patient-provider relationship. skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 179 such as clinician expertise and both the payer’s and provider’s history of “good-faith” practices. while “good-faith” practice is an ambiguous concept, policy analysts believe that this language may de-incentivize insurers from dropping clinicians from their networks.4 finally, the law introduces transparency provisions that will require providers to send “good faith estimates” to health plans or patients, if uninsured. the insurers will then provide an “advanced explanation of benefits” (eob) detailing network information, coverage, and out-ofpocket maximums to patients prior to service.3 while effects of this legislation on health insurance premiums, networks, physician reimbursement, and overall health care costs remain to be seen, we hope the added transparency and reform will be ultimately beneficial to patients. the american academy of dermatology is in support of measures to increase patient protection and is mindful of the legislation’s impact on compensation and administrative work. future research will be important to evaluate the law’s impact on dermatologist network participation and in-network prices. conflict of interest disclosures: none funding: none corresponding author: yuangao liu 1 baylor plaza houston, tx 77030 email: yuangaol@bcm.edu references: 1. joynt maddox ke, livingston e. surprise billing in surgery time for action. jama j am med assoc. 2020;323(6):547. doi:10.1001/jama.2019.21461 2. state balance-billing protections | commonwealth fund. accessed march 28, 2021. https://www.commonwealthfund.org/publications/ maps-and-interactives/2021/feb/state-balancebillingprotections?redirect_source=/publications/mapsand-interactives/2020/nov/state-balance-billingprotections 3. text h.r.133 116th congress (2019-2020): consolidated appropriations act, 2021 | congress.gov | library of congress. accessed january 27, 2022. https://www.congress.gov/bill/116thcongress/house-bill/133/text 4. chhabra kr, fuse brown e, ryan am. no more surprises — new legislation on out-of-network billing. n engl j med. 2021;384(15):1381-1383. doi:10.1056/nejmp2035905 mailto:yuangaol@bcm.edu mailto:yuangaol@bcm.edu skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 589 brief article the incidence of imprecise icd-10 coding in patients with cutaneous t-cell lymphoma: a marketscan database study ryan svoboda, md, ms1, haorui sun, bs2, steven maczuga, ms1, matthew helm, md1 1department of medicine, umass chan school of medicine, worchester, ma 2penn state college of medicine, hershey pa the term “primary cutaneous t-cell lymphoma” (primary ctcl) encompasses a heterogeneous group of non-hodgkin lymphomas which vary significantly in morphologic/histopathologic appearance, immunohistochemical profile, clinical behavior, and prognosis.1,2 although mycosis fungoides (mf) and sezary syndrome (ss) represent the prototypic and classic forms of ctcl, recent diagnostic advancements have led to expansion of the classification schema put forward by the world health organization and the european organization for research and treatment of cancer (who-eortc).3 therefore, more specific diagnoses should be used when possible and the overarching term, “ctcl,” should be avoided in clinical settings, as this does not refer to a distinct entity and can cause confusion for the patient and for other clinicians when used to indicate a more specific diagnosis such as mf.4 furthermore, the use of diagnosis codes for “ctcl” without more specific codes for individual entities can impact treatment and survival data and nullify the utility of claimsbased data used for research purposes, as previously demonstrated with other disease entities.5,6 consequently, our study aimed to determine the proportion of patients in the abstract background: the term “primary cutaneous t-cell lymphoma” (primary ctcl), although used largely interchangeably with mycosis fungoides in the past, actually represents numerous non-hodgkin lymphomas with highly variable and distinct characteristics. accuracy of claims-based research studies of ctcl hinge on the precision of icd-10 coding, but the incidence of imprecise coding for ctcl has not been extensively studied. objective: to determine the incidence of imprecise icd-10 coding in ctcl patients in a large, commercial claims database. methods: we analyzed the marketscan database from october 1, 2015 to december 31, 2018 to determine the proportion of patients designated only with the generic ctcl code in the absence of a code for a more specific diagnosis. results: of 3,953 patients meeting the criteria for inclusion, only 107 (2.7%) had a generic ctcl code without a more specific diagnosis code. conclusions: these results suggest that the majority of ctcl claims are precisely coded, although until future studies investigate the accuracy of diagnosis, the results of claims-based studies in the realm of ctcl should be interpreted with caution. introduction skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 590 marketscan database (ibm, armonk, ny) with any ctcl diagnosis who were designated only by the overarching “ctcl” code (c84.a0-a9) without a more specific code corresponding to an individual disease subtype. the marketscan commercial claims database was queried from october 1, 2015 to december 31, 2018. all patients ≥18 years of age with a new diagnosis of any ctcl (indicated by an icd-10 code for “ctcl” and/or a more specific ctcl subtype) with at least two outpatient encounters ≥6 months apart were included. the outcome of interest was the proportion of patients with encounters coded only with a generic “ctcl” icd-10 code without a more specific code corresponding to a specific subtype of ctcl (such as mf or subcutaneous panniculitislike t-cell lymphoma, for example). of 25,872,942 patients included in the marketscan database during the timeframe of this study, 3,953 patients carried at least one ctcl diagnosis code and met the criteria for inclusion. of these, only 406/3,953 (10.3%) had an encounter with a generic “ctcl” code listed (c84.a0-a9). furthermore, only 107/3,953 (2.7%) exclusively had a generic “ctcl” code without additionally having a more specific diagnosis code such as mf (c84.0-c84.9). the remainder, 3,846/3,953 (97.3%), had at least one code corresponding to a specific ctcl subtype (table 1). proper use of icd-10 diagnosis codes has important implications not only for billing, but also for claims-based research, as the validity of such studies hinges on the ability to identify a complete, homogenous sample population.5 this, in turn, depends on both the accuracy of diagnosis as well as the precision of coding (i.e. including codes for specific diagnoses when possible, and avoiding the sole use of “umbrella” codes for overarching disease categories). while the accuracy of diagnosis is not easy to assess through the use of a claims database, the precision of coding is. our study revealed, somewhat unexpectedly, that based on a large commercial claims database, the icd10 coding for primary cutaneous t-cell lymphomas is favorably precise and largely in line with the current who-eortc classification schema. this study has several limitations. first, due to the small number of patients meeting the criteria for conclusion, subgroup analysis aimed at comparing the precision of coding by geographic location or provider type (e.g. dermatologist vs. oncologist) was not possible. moreover, the marketscan database includes commercial claims only and therefore this data does not pertain to medicare/medicaid patients. additionally, although the majority of ctcl encounters are being coded precisely, this does not necessarily imply that these terms are being used properly in patient interactions. moreover, the precision of coding may not reflect accuracy of the diagnosis, which in terms of ctcl can be quite nuanced and cannot easily be assessed through the use of claims data. future studies aimed at assessing the accuracy of ctcl diagnosis/classification by different groups of clinicians should be performed. until such studies are undertaken, the results of any claims-based studies in the realm of ctcl methods results discussion skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 591 table 1. proportion of patients in market scan database with overarching “cutaneous t-cell lymphoma” and individual primary cutaneous lymphoma/lymphoproliferative disorder subtype diagnosis codes individual diagnosis codes for 2018 who-eortc entities ctcl icd-10 code (c84.a0, c84.a1, c84.a2, c84.a3, c84.a4, c84.a5, c84.a6, c84.a7, c84.a8, c84.a9) listed n, (%) ctcl icd-10 code (c84.a0, c84.a1, c84.a2, c84.a3, c84.a4, c84.a5, c84.a6, c84.a7, c84.a8, c84.a9) not listed n, (%) total n, (%) no individual entity code listed (see rows below) 107 (26.4%) 0 (0.0) 107 (2.7%) any individual entity code listed 299 (73.6%) 3,547 (100.0%) 3,846 (97.3%) individual entities*: mycosis fungoides (c84.0, c84.00, c84.01, c84.02, c84.03, c84.04, c84.05, c84.06, c84.07, c84.08, c84.09) 270 2,379 sezary syndrome (c84.10, c84.11, c84.12, c84.13, c84.14, c84.15, c84.16, c84.17, c84.18, c84.19) 24 124 adult t-cell leukemia/lymphoma (c91.50, c91.51, c91.52) 43 426 primary cutaneous cd30+ lymphoproliferative disorder/cutaneous anaplastic large cell lymphoma (c86.6) 43 633 subcutaneous panniculitis-like t-cell lymphoma (c86.3) 2 43 extranodal nk/t-cell lymphoma, nasal-type (c86.0) 0 101 primary cutaneous peripheral tcell lymphoma, nos (c84.48) 25 219 skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 592 table 2. current subtypes of cutaneous t-cell lymphoma (as defined by the 2018 update of the who-eortc classification for primary cutaneous lymphomas) and associated occurrence 2018 who-eortc ctcl subtypes distinct icd-10 code? approximate percentage of ctcl cases3 current “best” code in icd-10 mycosis fungoides yes 58% n/a sezary syndrome yes 2% n/a primary cutaneous anaplastic large cell lymphoma yes 10% n/a lymphomatoid papulosisa no (retired code)b 16% primary cutaneous cd30 positive lymphoproliferative disorder adult t-cell leukemia/lymphoma yes <1% n/a primary cutaneous cd4+ small/medium tcell lymphoproliferative disordera,c no 8% ptcl, nos subcutaneous panniculitis-like t-cell lymphoma yes 1% n/a extranodal nk/t-cell lymphoma, nasal type yes <1% n/a primary cutaneous γδ tcell lymphoma no <1% ptcl, nos cd8+ aggressive epidermotropic cytotoxic t-cell lymphomac no <1% ptcl, nos primary cutaneous acral cd8+ t-cell lymphomac no <1% ptcl, nos chronic active ebv infection no <1% ptcl, nos primary cutaneous peripheral t-cell lymphoma, nos yes 2% ptcl, nos alymphoproliferative disorder bprevious code retired, but could be coded as “cd30+ lymphoproliferative disorder,” which shares an icd-10 code with primary cutaneous anaplastic large cell lymphoma cprovisional entity in 2018 who-eortc classification for primary cutaneous lymphomas who=world health organization; eortc=european organization for the research and treatment of cancer; ebv=epsteinbarr virus; nk=natural killer; nos= not otherwise specified; pctl=peripheral t-cell lymphoma, n/a=not applicable skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 593 should be interpreted with an appropriate level of caution. the low incidence of imprecise icd-10 coding in patients with ctcl suggests that claims-based research studies in this population may be feasible which is important for these relatively rare diseases. specific icd-10 codes do not exist for some ctcl subtypes; this may account for a portion of the 2.7% of patients in this study with imprecise coding (table 2).3 consequently, icd-11 should incorporate specific codes for the newly-defined ctcl subtypes to help reduce the rate of imprecise coding even further. this will help to further refine the data gathered from clinical encounters, enabling more robust conclusions to be drawn from claims database studies performed in this population. conflict of interest disclosures: none funding: none corresponding author: ryan svoboda, md, ms department of medicine, umass chan school of medicine phone: (717) 531-6820 email: ryan.svoboda@umassmemorial.org references: 1. wilcox ra: cutaneous t-cell lymphoma: 2017 update on diagnosis, risk-stratification, and management. am j hematol 92:10851102, 2017 2. cerroni l: past, present and future of cutaneous lymphomas. semin diagn pathol 34:3-14, 2017 3. willemze r, cerroni l, kempf w, et al: the 2018 update of the who-eortc classification for primary cutaneous lymphomas. blood 133:1703-1714, 2019 4. zic ja: controversies in the management of the cutaneous t cell lymphomas. dermatologic therapy 22:407-417, 2009 5. chiu sy, shaw jw, luong tq, et al: coding patterns used by ophthalmologists for hydroxychloroquine retinal toxicity. clin ophthalmol 12:2261-2265, 2018 6. palestine ag, merrill pt, saleem sm, et al: assessing the precision of icd-10 codes for uveitis in 2 electronic health record systems. jama ophthalmol 136:1186-1190, 2018 conclusion skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 348 skimages diagnostic challenges of hypertrophic lupus erythematosus natalie garcia bs1, callie hill md2, victoria jiminez bs1, leah cardwell, md2, peter pavlidakey, md2, carlton b phillips, md2 1 university of alabama at birmingham school of medicine, birmingham, al 2 university of alabama at birmingham, department of dermatology, birmingham, al hypertrophic lupus erythematosus (hle), a variant of cutaneous le, often occurs in the absence of systemic symptoms and can be misdiagnosed as squamous cell carcinoma (scc) as both appear clinically as erythematous scaling plaques in sun exposed areas and histologically show significant epithelial hyperplasia.1 distinguishing hle from scc can be difficult, thus a detailed clinical history and adjunct testing to rule out inflammatory conditions are necessary to direct treatment. multiple clinical factors including a history of discoid lupus erythematosus, positive serologies, direct immunofluorescence studies, and anatomical location of the lesions on the face, arms, or chest, coupled with histological findings can lead pathologists to confidently diagnose hle; however, the absence of systemic symptoms in the clinical history often leads to misdiagnosis as squamous neoplasia.3 cd123 immunostains are helpful in diagnosing hle and should be considered for locally recurring presumed scc.2 a 76-year-old woman presented for evaluation of multiple well-differentiated sccs (wdscc) of the left lower leg. previous treatments included curettage, multiple mohs micrographic surgeries (mms), and topical fluorouracil resulting in more inflammation and pain. despite skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 349 surgical clearance, she developed new biopsy-proven wdscc near treated sites. she presented for a second opinion due to non-healing wounds and surgical fatigue. a trial of intralesional kenalog (ilk) injections significantly decreased pain and size of plaques. the patient had a negative past medical history of personal or familial autoimmune diseases, rash elsewhere, joint pain, and immunosuppression. examination showed erythematous, violaceous round plaques and smaller satellite papules with thin overlying scale coalescing on the left lower shin and erosions with yellow-brown crust on the lateral and medial aspect of the left lower leg. labs were negative for ana, ssa, and ssb. urinalysis was negative for blood and protein. ten prior left lower leg outside biopsies reported wdscc. a second-read revealed lichenoid dermatitis with pseudoepitheliomatous hyperplasia. due to her clinical course and differential including hle, immunostains were performed revealing cd123 positivity and increased peripheral epidermal plasmacytoid cells. cd123 tends to be more strongly positive in hle. at the bases of the rete pegs, there are interface changes throughout, especially at the base of the elongation. this tends to occur less frequently with scc. in some biopsies, follicular plugging was identified along with a subtle increase in dermal mucin. oftentimes, this will lead to a differential of hle vs hlp. in addition, eosinophils were identified which is often present in hypertrophic lupus and not hypertrophic lichen and planus. intralesional kenalog (0.5 cc of kenalog 20) was injected into 4 sites on the left lower leg. she was also given betamethasone 0.05% cream to apply twice daily to the affected areas of the left lower leg for 3 weeks. at 3-week follow-up, patient noted improvement in lesions evidenced by decrease in plaque size, erythema, and swelling. an additional 2.0 cc of kenalog 20 were injected, and she was started on daily triamcinolone 0.1% ointment. she was referred to rheumatologydermatology clinic and noted continued improvement with physical exam notable for atrophic pink plaques on the left lower leg, with no evidence of active disease. she was continued on triamcinolone 0.1% ointment skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 350 daily to the left lower leg as needed. these histological findings with improvement after ilk injections and topical steroids favored the diagnosis of hle. given the excellent cure rate of wdscc when treated appropriately, apparent recurrent local metastasis should prompt clinicians to rule out inflammatory processes, such as hle or hypertrophic lichen planus. diagnosing hle is difficult due to a lack of systemic symptoms and clinical and microscopic similarity to other cutaneous diseases. no single criterion confidently differentiates hle from scc histologically, postulating the need for cd123 immunostaining in evaluating locally recurring, supposed sccs.1 cd123 is highly expressed on the surface of plasmacytoid dendrocytes, seen in hle lesions densely at the epidermal-dermal junction, while scc lacks this positive band staining. recurrent lesions unresponsive to mms and positive cd123 immunostaining are highly suggestive of hle. conflict of interest disclosures: none funding: none corresponding author: natalie garcia, bs 1670 university blvd birmingham, al 35233 nhvoss@uab.edu references: 1. perniciaro, c. , randle, h. w. & perry, h. o. (1995). dermatologic surgery, 21 (3), 255-257. doi: 10.1111/j.1524-4725.1995.tb00167.x. 2. ko cj, srivastava b, braverman i, antaya rj, mcniff jm. hypertrophic lupus erythematosus: the diagnostic utility of cd123 staining. j cutan pathol. 2011 nov;38(11):889-92. doi: 10.1111/j.1600-0560.2011.01779.x. pmid: 21955314; pmcid: pmc4103013. 3. arps dp, patel rm. cutaneous hypertrophic lupus erythematosus: a challenging histopathologic diagnosis in the absence of clinical information. arch pathol lab med. 2013 sep;137(9):1205-10. doi: 10.5858/arpa.20130241-cr. pmid: 23991731. mailto:nhvoss@uab.edu skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 69 brief article segmental kaposi sarcoma in an immunocompromised patient lori s. kim, ba1, erin dodd, md2, angad a. chadha, md2 1 university of illinois at chicago college of medicine, chicago, il 2 section of dermatology, university of chicago, chicago, il kaposi’s sarcoma (ks) is a low-grade vascular tumor that has been reported with frequency in immunocompromised patients. there are four clinical variants: classical, endemic (or african), aids-associated, and iatrogenic immunosuppression-associated ks.1 although the clinical presentation of ks varies amongst these clinical variants, ks typically presents with violaceous macules, papules, and plaques on the bilateral lower extremities, face, and oral mucosa.2 extracutaneous manifestations most often present in the gastrointestinal tract and respiratory system it is exceedingly rare for ks to be localized to a solitary body segment that is not located on the lower extremities. we report a case of an immunocompromised organ transplant patient who developed ks in a segmental distribution of his left flank. the inpatient dermatology consult service was consulted on a 60-year-old caucasian male with a history of a bilateral lung transplant, now presenting with a rash on the left abdomen that started a few weeks prior. he denied any pain or pruritus and denied any similar rashes in the past. he did not report any rash anywhere else on his body, including any oral or genital lesions. his contributory medications included posttransplant immunosuppression with azathioprine, tacrolimus, and prednisone. on exam, the patient had numerous nontender, non-blanching, violaceous ovoid papulonodules and patches scattered only on the left lateral abdomen with few ecchymoses (figure 1). a skin biopsy of one of the papulonodules showed a spindle cell proliferation in the dermis forming sheets and fascicles with slit-like spaces filled with red blood cells, compatible with a diagnosis of kaposi sarcoma. human herpesvirus 8 abstract kaposi sarcoma (ks) is a vascular tumor that classically presents as multiple violaceous lesions on the extremities in a widespread manner. a 60-year-old male with a history of immunosuppression in the setting of bilateral lung transplant presented with numerous violaceous papulonodules and patches localized on the left flank, with a biopsy confirming the diagnosis of ks. we present a rare case of ks presenting in a segmental distribution and review the available literature with a discussion of the possible mechanisms behind segmental and dermatomal ks. introduction case presentation skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 70 immunostaining was positive in the neoplastic cells. fecal occult blood testing was negative. chest x-ray at that time demonstrated widespread interstitial edema and bilateral pleural effusions thought to be due to volume overload but the possibility of pulmonary ks was not radiographically ruled out. figure 1 the patient was not a candidate for local treatments alone due to the number of lesions; he was originally discharged with plans to adjust his immunosuppression and assess ks response before considering local therapies. outpatient pet/ct was to be pursued. however, 3 weeks later the patient was readmitted for type 1 respiratory failure requiring intubation after a routine bronchoscopy. at that time, a ct scan of the chest revealed bilateral ground-glass pulmonary opacities with moderate pleural effusions; this was thought to likely be multifactorial due to pneumonia and possibly rapidly progressing ks. given the patient’s tenuous clinical status and difficulty obtaining a lung biopsy, he was treated empirically with broad-spectrum antimicrobials and soon thereafter with intravenous liposomal doxorubicin for possible ks. eventually, due to lack of clinical response, trans-bronchial lung biopsy was pursued and revealed acute fibrinous and organizing pneumonia without evidence of ks in the lungs. soon after the biopsy, the patient was placed on continuous veno-venous hemodialysis (cvvhd) due to severe acute kidney injury and thereafter placed on veno-venous extra corporeal membrane oxygenation (ecmo) due to declining lung function. the patient’s family ultimately decided to transition the patient to comfort care; he expired shortly thereafter. here we present a case of segmental ks in a patient on iatrogenic immunosuppression after lung transplant. given that ks is more often found on the legs and face, this is a relatively rare presentation of this disease. a dermatomal presentation of ks was first documented by niedt, who presented a patient with a history of intravenous drug use who developed herpes zoster infection in the left t3 distribution and then two months lateral developed ks in the same distribution.4 niedt proposed that this presentation was due to the koebner phenomenon, which is when a previously present disease recurs in a site of trauma.4 the koebner phenomenon was further elucidated by wolf, who coined the term wolf’s isotopic response.5 whereas koebner’s isomorphic phenomenon describes the appearance of a skin lesion that is morphologically similar to an existing skin disease at a site of injury, wolf’s discussion skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 71 isotopic response describes the occurrence of a new, unrelated disease that appears at the same site of a previously healed disease.5 numerous postherpetic isotopic responses have been documented, including but not limited to granuloma annulare, breast carcinoma, leukemic infiltration, and lichen planus; however, ks is extremely rare in that the case report by niedt is the only documented so far.4,6,7 our patient's presentation cannot quite be explained by either the koebner phenomenon or wolf's isotopic response, as he did not report a previous history of herpes zoster virus (hzv) or other rashes at the site of his ks. a similar case was reported by eisman, who documented a patient presenting with ks on his right lower leg and right chest in a t5 dermatone distribution without any history of previous hzv.8 one of the mechanisms he proposed was “locus minoris resistentiae" which describes eczematous eruptions that develop in areas of previously injured skin, broadly including any history of surgery, trauma, or scar.9 this certainly might be possible for our patient who had a bilateral lung transplant but would be unusual as the ks presented more on his flank rather than the site of surgery. the review article on the postherpetic isotopic response by ruocco describes several possible pathogenetic mechanisms of wolf’s isotopic response including viral, immunologic, vascular, and neural origin.6 of these, the neural etiology is of particular interest as it hypothesizes that underlying neurologic alteration with consequent immunologic impairment is the first step in the isotopic response.6 this consequently raises the possibility of ks appearing as wolf's isotopic response within an area previously affected by "zoster sine herpete" which could have occurred sub-clinically without the patient’s knowledge. this proposed relationship between neurologic alteration, immunology, and the skin may give us a better insight into our patient's presentation, given his segmental ks presentation and his history of immunosuppression. we present a case of an immunosuppressed patient who developed ks in an unusual segmental distribution. additionally, we provide a literature review of the limited reported cases of segmental and dermatomal ks, with emphasis placed on the possible pathophysiology behind this presentation. conflict of interest disclosures: none funding: none corresponding author: angad a chadha, md 5841 s maryland ave mc 5067 chicago, il 60637 phone 773-702-1611 fax 773-834-7071 email: chadha@uchicago.edu references: 1. fitzpatrick’s dermatology, 9e | accessmedicine | mcgraw-hill medical. accessed march 16, 2021. https://accessmedicine.mhmedical.com/book.asp x?bookid=2570 2. radu o, pantanowitz l. kaposi sarcoma. archives of pathology & laboratory medicine. 2013;137(2):289-294. doi:10.5858/arpa.20120101-rs 3. beasley mb, franks tj, galvin jr, gochuico b, travis wd. acute fibrinous and organizing pneumonia: a histological pattern of lung injury and possible variant of diffuse alveolar damage. arch pathol lab med. 2002;126(9):1064-1070. doi:10.1043/00039985(2002)126<1064:afaop>2.0.co;2 4. william niedt g, prioleau pg. kaposi’s sarcoma occurring in a dermatome previously involved by conclusion mailto:chadha@uchicago.edu skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 72 herpes zoster. journal of the american academy of dermatology. 1988;18(2):448-451. doi:10.1016/s0190-9622(88)70068-7 5. wolf r, brenner s, ruocco v, filioli fg. isotopic response. int j dermatol. 1995;34(5):341-348. doi:10.1111/j.13654362.1995.tb03616.x 6. ruoccoa v, ruoccoa e, ghersetichb i, bianchib b, lottib t. isotopic response after herpesvirus infection: an update. journal of the american academy of dermatology. 2002;46(1):90-94. doi:10.1067/mjd.2002.118362 7. wang t, zhang m, zhang y, et al. wolf’s isotopic response after herpes zoster infection: a study of 24 new cases and literature review. acta derm venerol. 2019;99(11):953-959. doi:10.2340/00015555-3269 8. eisman s, o’toole ea, collis c, rustin mha. zosteriform kaposi’s sarcoma. clinical and experimental dermatology. 2001;26(5):402-404. doi:https://doi.org/10.1046/j.13652230.2001.00845.x 9. dermatitis in loco minoris resistentiae. journal of the american academy of dermatology. 1982;6(6):1010-1013. doi:10.1016/s01909622(82)80099-6 skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 87 editorial using genomics to improve pigmented lesion management & health outcomes clay cockerell, md1, roger ceilley md2, mark lebwohl, md3, darrell rigel, md, ms3 1 university of texas southwestern medical center, dallas, tx 2 university of iowa school of medicine, des moines, ia 3 icahn school of medicine at mount sinai, new york, ny the advantage of a noninvasive test that reduces unnecessary biopsies is obvious. in managing pigmented lesions, us dermatologists biopsy about 5 million uncertain lesions annually to identify around 200,000 in situ and invasive melanomas (number needed to biopsy=25).1, 2 current practice relies on visual assessment with or without dermoscopy to determine which pigmented lesions warrant biopsy and histopathology. the current issue of skin presents a costbenefit analysis of a non-invasive 2-gene expression profile (2-gep) (pigmented lesion assay [pla] dermtech, la jolla, ca), which studies have demonstrated has a >99% negative predictive value (npv).3 with the ability to detect genomic atypia in pigmented lesions, this technology offers an additional tool to clinicians faced with the conundrum of determining whether a pigmented lesion should be biopsied/removed or if they can be safely monitored.4 the validity and utility of the test has been established in over 20 peer reviewed publications; however, its impact on healthcare delivery cost has to date only been considered in one earlier publication focused on medicare patients.5 in this issue of skin, siegel et al. provide an analysis of cost savings to commercial payors on this test that facilitates early detection and guides biopsy decisions. their model demonstrates that adding detection of genomic atypia to visual assessment to make critical pre-biopsy management decisions has the potential to improve care while also reducing costs. siegel and colleagues present a return on investment (roi) model from a us payor perspective to evaluate the potential savings to commercial health plans if genomic atypia detection with 2-gep is incorporated into the current visual assessment/histopathology (vah) pathway for pigmented lesions uncertain for melanoma. using 2019 optum group claims data encompassing 239,854 patients with lesions suspicious for melanoma, costs were assessed through the pathway of initial visual assessment, surgical procedure(s), histopathology, and subsequent management. the roi model predicted annual net savings of $0.54 per member per month for commercial health plans over a three-year period with incorporation of the 2-gep test into the vah pathway. their findings suggest that for a plan with 1 million covered lives, this translates into potential aggregate savings of $5.66 million over three years. skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 88 siegel et al. also showed high rates of biopsies and excisions on benign lesions using the vah pathway, which highlights the need for more accurate clinical assessment of pigmented lesions. in their analysis using this clinical setting, 95.7% of surgically assessed lesions clinically suspicious for melanoma were diagnosed as benign, and 30.4% of patients with benign lesions undergoing a more advanced procedure such as an excision, either initially or following a biopsy. melanoma diagnosis rates were 0.9% with biopsy only, 0.1% with excision only, and 17.9% with a biopsy followed by excision procedures. with access to objective genomic information such as that provided by the 2-gep test, there is the opportunity to better identify which patients are most likely to benefit from a procedure for further evaluation of their lesions. these healthcare economic analyses are complemented by another recent publication in skin by skelsey et al. on the performance of 2-gep and its utility in intended use populations.6 that study confirmed a npv >99% in real world settings and a positive predictive value (ppv) of 18.7%, which is an approximately 5-fold improvement over visual assessment alone.7 real-world npv was determined by long-term follow-up of two cohorts of lesions that tested negative on the 2-gep and were not initially biopsied. out of 1,535 total lesions followed, 13 early-stage melanomas (7 in situ, 6 stage pt1a) were identified up to 3 years after the initial negative test result, corresponding to a real-world npv of >99%. real-world ppv was determined by identifying melanoma diagnoses among 316 lesions that tested positive on the 2-gep within a us-based registry. of the 316 2gep positive cases, 59 were diagnosed as melanoma by histopathology, corresponding to a ppv of 18.7%. of all 2-gep positive lesions, 30.5% had histopathologic diagnoses corresponding to high-risk mpath-dx categories (classes iii-v, including severely dysplastic nevi, in situ melanomas, and invasive melanomas), demonstrating the ability of this technique to detect high-risk lesions such as dysplastic nevi with severe or high-grade atypia that are generally targeted for complete excision. taken together, these data indicate that the 2-gep test is highly reliable for ruling out melanoma and can also enhance our individual and collective number needed to biopsy to detect melanoma. these 2 studies suggest that incorporation of 2-gep analyses into the vah pathway for assessing clinically suspicious pigmented lesions can result in savings for both cms and commercial health insurance plans.5 use of the 2-gep improves patient care and improves health outcomes by using genomic assessments to minimize avoidable surgical procedures on benign lesions, enriching the population of melanomas within biopsied lesions, and decreasing downstream costs of late-stage melanoma diagnoses. for all of these reasons, creating broad access and coverage to transformative diagnostic technologies such as the 2-gep is in the best interest of our colleagues, the healthcare system, and most importantly, our patients. conflict of interest disclosures: dr. rigel and dr. cockerell have served as consultants for dermtech. funding: none corresponding author: darrell rigel, md, ms email: darrell.rigel@gmail.com references: 1. anderson am, matsumoto m, saul mi, secrest am, ferris lk. accuracy of skin cancer diagnosis by physician assistants compared with dermatologists in a large health care skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 89 system. jama dermatol. may 1 2018;154(5):569-573. doi:10.1001/jamadermatol.2018.0212 2. siegel rl, miller kd, fuchs he, jemal a. cancer statistics, 2021. ca: a cancer journal for clinicians. 2021;71(1):7-33. doi:https://doi.org/10.3322/caac.21654 3. gerami p, yao z, polsky d, et al. development and validation of a noninvasive 2-gene molecular assay for cutaneous melanoma. j am acad dermatol. jan 2017;76(1):114-120 e2. doi:10.1016/j.jaad.2016.07.038 4. data on file. dermtech, inc. la jolla, california. 5. hornberger j, siegel dm. economic analysis of a noninvasive molecular pathologic assay for pigmented skin lesions. jama dermatol. sep 1 2018;154(9):1025-1031. doi:10.1001/jamadermatol.2018.1764 6. skelsey m, brouha b, rock j, et al. non-invasive detection of genomic atypia increases realworld npv and ppv of the melanoma diagnostic pathway and reduces biopsy burden. skin the journal of cutaneous medicine. 2021;5(5):512523. 7. lott jp, boudreau dm, barnhill rl, et al. population-based analysis of histologically confirmed melanocytic proliferations using natural language processing. jama dermatol. jan 1 2018;154(1):24-29. doi:10.1001/jamadermatol.2017.4060 https://doi.org/10.3322/caac.21654 skin july 2021 1244 proof skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 399 research letter characterization of clinical outcomes in patients with cutis marmorata telangiectatica congenita nathan l. bowers, md, phd1, wasim haidari, md1, jennifer j. su, bs1, jesus a. cardenas-de la garza, md1,2, steven r. feldman, md, phd1,3,4, joseph l. jorizzo, md1 1center for dermatology research, department of dermatology, wake forest school of medicine, winston-salem, nc 2department of dermatology, university hospital "dr. jose eleuterio gonzalez", universidad autonoma de nuevo leon, monterrey, mexico 3departments of pathology and social sciences & health policy, wake forest school of medicine, winston-salem, nc 4department of dermatology, university of southern denmark, odense, denmark cutis marmorata telangiectatica congenita (cmtc) is an uncommon, congenital, cutaneous vascular disease. the pathogenesis of cmtc remains unknown. although considered as a benign condition, anomalies such as body asymmetry, vascular lesions, neurological and ophthalmic manifestations, hypoplasias/aplasias are frequently associated. however, whether these associations are due to reporting bias is a matter of debate. this study evaluated cmtc patients seen at our institution and examined their clinical outcomes. the wake forest baptist health institutional review board (winston-salem, north carolina) approved this single-institution retrospective medical record review. inclusion criteria included patients 18 years or younger diagnosed with cmtc from july 2009 – july 2019. patients with cmtc were identified using icd-19 code: 757.32 and icd-10 codes: q82.8 and r23.9. patients with physiologic cutis marmorata were excluded. primary outcome measures were presence of associated anomalies and improvement of skin over time. demographics collected included age, sex, and race. information on anatomic distribution of skin lesions was also extracted. seventeen patients were identified using the inclusion criteria. all cases had parental reports of skin lesions present at or shortly abstract cutis marmorata telangiectatica congenita (cmtc) is an uncommon, congenital, cutaneous vascular disease with an unknown pathogenesis. although considered as a benign condition, anomalies such as body asymmetry are frequently associated. herein we present a series of patients with diagnosis of cmtc with a focus on clinical outcomes. in our series, limb length abnormalities were the most common associate anomaly, occurring in 24% of the subjects, similar to other series with rates of 33% and 27% but higher than the general population (6.7%). importantly, dermatologists should be aware of the frequently associated anomalies in cmtc, such as leg length discrepancy, which may have serious consequences if not recognize and treated. skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 400 table 1. patient demographics and clinical characteristics patient no. sex age at diagnosis age at most recent follow-up associated signs/ symptoms associated anomalies improvement of skin over time 1 f 15 y/o no followup raynaud's-like phenomenon no 2 m 7 y/o 12 y/o varicose veins hypertrophy of 2nd toes (bilateral), and pectus excavatum yes 3 m 17 mo. 4 y/o leg asymmetry, port wine stain no 4 m 8 mo. 2 y/o phakomatosis pigmentovascularis (cmtc + mongolian spot), ocular melanosis, nevus spilus yes 5 f 4 mo. 7 mo. atrophy yes 6 m 16 mo. 22 mo. hamartoma yes 7 f 4 mo. 16 mo. connective tissue nevus yes 8 f 10 days 2 y/o swelling, pain, and difficulty walking speech delay, congenital umbilical hernia, ash-leaf spot vs nevus anemicus yes, but pain worsened 9 m 4 mo. no followup leg asymmetry yes 10 m 2 y/o no followup bilateral hearing loss, wheezing, dysphagia yes 11 f 2 mo. 15 mo. yes 12 m 2 mo. no followup yes 13 m 10 mo. 16 mo. yes 14 f 3 mo. 6 mo. port wine stain yes 15 m 15 y/o no followup pain, ulceration, atrophy no 16 f 1 mo. 6 y/o pain leg circumference asymmetry (10mm), minimal limb length difference (4mm) no 17 f 5 mo. 3 y/o pain, swelling, limping vein asymmetry no after birth. both genders were equally affected (table 1). nine patients (53%) had only one affected limb (table 2). twelve cases (71%) reported fading of skin lesions over time. four patients (24%) reported pain due to skin atrophy or limb discrepancy. body asymmetry was present in five subjects (29%). six subjects (35%) had another dermatosis, most commonly a port-wine stain (12%) (table 1). half of those who received a magnetic resonance imaging (mri) scan (2 out of 4 subjects) had normal findings. the scans of the other two patients revealed increased number of venous structures and venous malformations with asymmetry of the greater and lesser saphenous veins. the low prevalence of cmtc makes information on its clinical characteristics and associations limited. the rate of complications and associated abnormalities reported is highly variable ranging 18-80%. due to different reporting methodologies and inclusion of abnormalities which are prevalent in the general population, the higher rate may be secondary to incidental or skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 401 questionable findings.(1-3) recent reports have characterized limb length discrepancy and other congenital vascular abnormalities as the most frequent associations.(3-5) in our series, limb length abnormalities were present in 24% of the subjects, similar to other series with rates of 33% and 27% but higher than the general population (6.7%).(4, 6) because of possible reporting bias, the relative proportion of limb length abnormalities related to cmtc diagnosis is controversial. limb measurement is recommended to be assessed and documented in each evaluation. most cases are mild (<2cm difference) and do not require additional intervention other than follow-up. discrepancies ≥2cm may require pediatric orthopedic evaluation. overall, the orthopedic prognosis is good and only a minority of subjects require surgical intervention. (4) also consistent with other series, most patient records (71%) noted that their lesions faded over time (3). we predict the true rate of improvement is higher due to lack of follow-up for asymptomatic courses of cmtc. limitation of this study are its retrospective design, reliance on clinicians reporting their findings, small sample size, and limited duration of follow-up. cmtc is a relatively benign disorder on its own, which does not usually require treatment. health care professionals should be aware of the frequently associated anomalies, such as leg length discrepancy, which may have serious consequences if not recognized and treated. children with cmtc on their legs should have regularly monitoring for leg length discrepancy during childhood. improvement of marbled skin appearance occurs in the majority of patients over time, and improvement is likely higher than reported due to lack of follow-up reporting for asymptomatic courses of cmtc. table 2: distribution of skin lesions patient no. ue le abdomen/ chest back face 1 x 2 xx xx x 3 xx x x x x 4 xx xx x 5 x 6 x 7 x 8 x 9 x x x 10 x 11 x 12 x x 13 x 14 x x x 15 x 16 x 17 x xx: bilateral le – lower extremity; ue – upper extremity conflict of interest disclosures: feldman has received research, speaking and/or consulting support from a variety of companies including galderma, gsk/stiefel, almirall, leo pharma, boehringer ingelheim, mylan, celgene, pfizer, valeant, abbvie, samsung, janssen, lilly, menlo, merck, novartis, regeneron, sanofi, novan, qurient, national biological corporation, caremark, advance medical, sun pharma, suncare research, informa, uptodate and national psoriasis foundation. he is founder and majority owner of www.drscore.com and founder and part owner of causa research, a company dedicated to enhancing patients’ adherence to treatment. wasim haidari, jennifer su, dr. cardenas-de la garza, dr. bowers have no conflicts to disclose. funding: none corresponding author: nathan l. bowers, md, phd department of dermatology wake forest school of medicine medical center boulevard winston-salem, nc 27157-1071 phone: 336-716-7740, fax: 336-716-7732, e-mail : nbowers@wakehealth.edu skin july 2021 volume 5 issue 4 copyright 2021 the national society for cutaneous medicine 402 references: 1. devillers ac, de waard-van der spek fb, oranje ap. cutis marmorata telangiectatica congenita: clinical features in 35 cases. arch dermatol. 1999;135(1):34-8. 2. amitai db, fichman s, merlob p, morad y, lapidoth m, metzker a. cutis marmorata telangiectatica congenita: clinical findings in 85 patients. pediatr dermatol. 2000;17(2):100-4. 3. kienast ak, hoeger ph. cutis marmorata telangiectatica congenita: a prospective study of 27 cases and review of the literature with proposal of diagnostic criteria. clin exp dermatol. 2009;34(3):319-23. 4. memarzadeh a, pengas i, syed s, eastwood dm. limb length discrepancy in cutis marmorata telangiectatica congenita: an audit of assessment and management in a multidisciplinary setting. br j dermatol. 2014;170(3):681-6. 5. del boz gonzalez j, serrano martin mm, vera casano a. [cutis marmorata telangiectatica congenita. review of 33 cases]. an pediatr (barc). 2008;69(6):557-64. 6. drnach m, kreger a, corliss c, kocher d. limb length discrepancies among 8to 12-year-old children who are developing typically. pediatr phys ther. 2012;24(4):334-7. skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 365 in-depth review nonthermal atmospheric pressure plasma technology in dermatology chelsea shope, mscr1, tyler beck, bs1, laura andrews, mscr1, peter c. friedman, md, phd2, lara wine lee, md, phd3 1 college of medicine, medical university of south carolina, charleson, sc 2 the skin center dermatology group, new city, ny 3 department of dermatology & pediatrics, medical university of south carolina, charleston, sc in the past 20 years, significant advancements have been made in the understanding of physical plasma. the advent of nonthermal atmospheric plasma (ntap) devices has spurred the advancement of applications of physical plasma in medicine, especially in the field of dermatology. plasma is known to cause cell membrane permeabilization, regulate skin regeneration, and offer both antibacterial and antiviral properties.1-3 in this review, we discuss recent applications in the treatment of skin conditions. nonthermal atmospheric plasma the concept of “plasma” in the world of physics refers to an ionized gas. physical plasma exists in a higher energy state than normal gas, which allows for electrons and ions to move independently of one another. plasma can be further subdivided into “hot” and “cold” plasma. hot plasma occurs when electrons and ions are in energy equilibrium with one another. while applications for hot plasma exist in the medical field, they are mostly limited to surgical tools. ntap, which abstract nonthermal atmospheric plasma (ntap), also known as cold atmospheric plasma (cap), is an emerging tool with important effects on biological systems. ntap harnesses physical plasma, generating a low energy ion environment in which reactive oxygen and nitrogen species are formed. these ionic species can modify proteins and cell membranes in a noninvasive manner. the use of ntap therapy, a technology once used for medical sterilization, is rapidly expanding, particularly in the field of dermatology. in addition to potent anti-microbial properties, ntap has demonstrated promise in skin regeneration and cancer-related indications. ntap affords a unique advantage to pharmacological therapies in that there is no risk of drug-drug interactions. a preliminary safety profile for ntap has been established, with no adverse effects such as pain, inflammation, blistering, bruising, and pruritus noted to date. in this review, we discuss the clinical application of ntap in the treatment of onychomycosis, warts, actinic keratosis, and wound healing. introduction review skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 366 is also known as cold atmospheric plasma (cap) or non-equilibrium plasma, refers to plasma that is not in thermodynamic equilibrium, as only the electrons are at a very high temperature, while the ions are at lower temperature. as electrons are quite small, it is the ion component of plasma that makes up the significant portion of its mass. when electrons are thermalized, their velocity distribution is very different from that of the ion velocity distribution, which leads to modification in proteins and cell membranes. cold plasma is room temperature and therefore does not cause thermal injury to the skin or skin functions, indicating a very favorable safety profile for its application in treating cutaneous pathologies.4,5 plasma can be created in a vacuum, or under atmospheric pressure conditions. the majority of ntap is generated in air, helium, or argon mixed with other reactive gases.6 this creates a low energy ion environment in which reactive oxygen and nitrogen species (ros and rns, respectively) are formed, along with other plasma components such as uv photons and hydroxyl radicals.7 plasma affects cells in a dosage-dependent manner by disrupting cell-cell adhesions and cell detachment from substrates.1 the short-term exposure temporarily causes cell membrane permeabilization, which inhibits cell migration. longer exposure times and higher intensity plasma induces apoptosis or necrosis by ros and rns. while ntap has complex effects on tissues, the ros and rns generated contribute to an antiviral and antibacterial milieu,2 allowing plasma to alter tissues at the cellular level, without causing additional damage.7 several additional cellular and molecular mechanisms that modulate the biological effects of ntap therapy have been elucidated. the wingless-int (wnt)/β-catenin signaling pathway has been reported as the major regulator of skin regeneration following ntap treatment.8 β-catenin is a transcriptional factor that positively regulates wnt signaling, playing an important role in stem cell renewal, cell proliferation, and cell survival.9 moreover, in vitro application of ntap therapy to keratinocytes in culture stimulated cell growth and proliferation, as evidenced by increases in the proportion of treated cells in s and g2 phase.8 additionally, ntap treatment disrupted ecadherin mediated cell-to-cell interactions, allowing for increased nuclear localization of β-catenin. increased nuclear presence of βcatenin increased the transcription of c-myc and cyclin d1, further supporting the increases in cell growth, proliferation, and overall “cell stemness” observed. these findings were recapitulated in vivo, supporting ntap mediated epidermal expansion and increases in activated βcatenin in the absence of dna damage. ntap induction of cell stemness is an exciting finding that demonstrates great promise for dermatological applications. interestingly, despite demonstrating the capacity to promote cell growth and proliferation, ntap has demonstrated efficacy in the treatment of cutaneous malignancies, such as in vitro melanoma and squamous cell carcinoma. longer ntap exposures disrupt calcium homeostasis in cancer cells, leading to increased intracellular calcium levels.10 calcium is a critical secondary messenger responsible for regulating tumor survival, growth, and invasion. additionally, calcium plays a critical role in triggering mitochondrial cytochrome c release and subsequent apoptosis in cells experiencing extreme stress. prolonged ntap exposure induced apoptotic behavior in melanoma cells in the presence of increased intracellular calcium. evidence suggests skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 367 ros and rns mediated disruption in cellular calcium handling may play a critical role in ntap-mediated anti-cancer activity. further evidence of ntap activity will be provided in this review. nonthermal plasma technology biomedical application of physical plasma at lower temperature has been regarded as one of the most significant opportunities for advancement in plasma science. ntap allows for the direct delivery of cold plasma to the skin’s surface without the burden of a vacuum chamber or the need to burn tissue.11 ntap has a broad range of applications from disinfection of living tissues, to blood coagulation, to the induction of apoptosis in malignant tissues.6,12-15 the first small scale clinical studies have shown plasma treatments to be well tolerated, painless and without side effects.4,16-21 in a risk assessment of uv radiation and temperature, it was shown that the uv radiation generated by plasma is an order of magnitude lower than the minimal erythema dose (med) necessary to produce sunburn on the skin in vivo. further, thermal damage of tissues by plasma can be eliminated due to the nature of cold plasma. plasma is non-toxic and chemical-free, and devices may be used for multiple years. thus, ntap devices results in a significant reduction of effluents, which is beneficial from both an economic and environmental perspective.22 nonthermal atmospheric plasma devices three types of ntap devices exist: the floating electrode-dielectric barrier device (fe-dbd), which supplies direct plasma; atmospheric pressure plasma jet (appj), which indirectly supplies plasma; and the surface microdischarge device, which is a hybrid of fe-dbd and appj. the individual plasma devices and their differences are reviewed extensively elsewhere.23 most of the literature regarding ntap centers on appj, which has been studied extensively with ulcer and wound healing. for this review, we focus on fe-dbd, which is increasingly being used as the ntap system of choice in dermatology. fe-dbd creates plasma using a pulse generator. for a typical fe-dbd used in dermatology, this pulse generator supplies a 20-kv pulse of 20-ns pulse width at 200 hz to a 5-mm diameter quartz-covered copper electrode of 10-cm length and 1-mm quartz thickness [figure 1].13 these nanosecond pulse parameters offer a high level of plasma uniformity which allows for the avoidance of tissue damage. however, this is but one example of fe-dbd. lipner’s study of onychomycosis used a machine with a different electrode shape and size, as well as different settings.24 for in vitro and animal studies, there are many variations of electrode design and pulse generator settings. figure 1. floating electrode-dielectric barrier device skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 368 plasma devices use a variety of feed gases, such as atmospheric air, argon, and helium; however, ntap generates plasma using air or helium. during the generation of plasma, there is no electric contact with the tissue being treated. the flow of the gas is slow, thus there is no mechanical effect on tissue. applications in dermatology treatment with ntap has been shown to be well tolerated and without adverse effects on the skin, even on skin surfaces that are denuded, eroded, or ulcerated. given its outstanding safety profile and painlessness of application, ntap technology has been employed in a variety of dermatologic clinical studies. these studies have investigated the treatment of onychomycosis, actinic keratosis, warts, and wound healing.25 onychomycosis ntap has demonstrated efficacy in vitro and in vivo in the treatment of onychomycosis.13,24,25 onychomycosis is a fungal infection of the nails, commonly caused by dermatophytes of the trichophyton genus.26 treatment of onychomycosis typically involves the use of systemic anti-fungal agents, such as terbinafine , and/or topical antimicrobials. oral antifungal agents can promote significant drug-drug interactions and undesirable side effects, whereas topical treatments have low complete cure rates.27,28 additionally, these agents require long-term daily administration. as such, there is an unmet need for a quick, noninvasive, and efficacious treatment for onychomycosis. in vitro studies assessing dermatophyte inactivation by ntap demonstrated significant sensitivity to plasma therapy, providing rationale for clinical studies. a study by xiong et al. examined the efficacy of ntap in treating model nails coated with either escherichia coli (e. coli) bacteria or trichophyton rubrum (t. rubrum) fungus.13 three different ntap devices were employed: helium plasma jet, surface micro discharge plasma, and fe-dbd. all three ntap devices significantly reduced bacterial and fungal load on the nail surface; however, the fe-bdd significantly outperformed all ntap devices. in a pilot study of 13 patients with toenail onychomycosis, there was a 53% clinical and 15% mycological cure rate with no side effects when using ntap.24 clinical cure was defined as a 3-5 mm increase in clear nail six-months following treatment. notably, 61.5% of patients were satisfied with their treatment; 76.9% of patients expressed willingness to pay for ntap treatment, and 100% of patients felt that treatment was tolerable. these data establish a clinical benefit of ntap in treating onychomycosis and support the need for larger clinical studies. actinic keratosis actinic keratoses (aks) are precursor lesions to squamous cell carcinoma (scc) that are commonly associated with chronic sun exposure. aks are typically treated with blue light therapy or topical compositions containing 5-fluorouracil, depending on lesion location and thickness. conventional treatments have drawbacks, such as treatment site pain and inflammation; incomplete resolution of the lesion, and frequent recurrence of the lesion.13 in vitro studies have demonstrated a pro-apoptotic benefit of ntap in scc cells derived from patient tumors. additionally, ntap therapy promotes macrophage migration and activation in vitro, suggestive of a potential immune-mediated attack of pre-cancerous skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 369 cells in target lesions.12,13,29 these data have inspired clinical studies involving the use of ntap in treating patients with aks. a clinical study involving the use of electrical plasma, a form of ntap, demonstrated efficacy in the treatment of aks.12,30 five patients were enrolled in a pilot study, comprising 17 lesions. patients underwent a single ntap treatment to each lesion with one-month follow-up. preand one-monthpost-treatment images were compared. treatment outcomes were stratified into one of three categories: fully resolved, significant improvement (>50% regression), or no improvement (<50% regression). of the 17 lesions studied, nine lesions (53%) completely resolved; five lesions demonstrated significant improvement (29%), and three lesions were unchanged (18%). overall, 70% of lesions demonstrated a therapeutic benefit without discomfort during or after treatment. these data suggest a role for ntap in the treatment of aks and th need for follow-up studies in larger patient populations. a clinical study using appj also demonstrated efficacy for ntap in the treatment of aks.31 this proof-of-concept study enrolled seven patients with a total of 115 lesions treated over eight treatment areas. patients underwent a total of seven treatments applied twice weekly for two minutes each. olsen grading preand posttreatment were compared. clinical downgrading as per olsen was found in all treated areas, indicating a decline in ak characteristics such as erythema, scaling, crusts, and thickness. the total lesion number decreased in 75% of the treated areas. no adverse events were observed. these data suggest that ntap may represent a novel, safe treatment that lacks side-effects, though prospective clinical trials with long-term follow-up are needed. a similarly appj-based study demonstrated the effectiveness of ntap in treating multiple aks, as measured using highfrequency ultrasound (hfus).32 twelve patients with multiple aks of the face and scalp who were either intolerant or resistant to conventional field-directed treatments underwent twice weekly sessions of ntap for two minutes. treatment was performed until lesion resolution or a maximum of seven weeks of treatment was reached. performance indexes were determined using three-dimensional digital pictures at baseline and three months post-treatment. all clinical variables, including number of lesions, cumulative area of aks, and the actinic keratosis area and severity index, showed a significant reduction following ntap. hfus revealed that total, epidermal, and dermal thickness of target aks did not change with treatment. instead, ntap significantly increased dermal density of target aks and surrounding sun damaged skin, and significantly decreased the thickness of the subepidermal lowechogenic band in perilesional skin. this band represents an ultrasound sign of sun damage. this was the first clinical study using evaluation other than observation alone to demonstrate the efficacy of ntap. ntap has proven to be as effective as diclofenac 3% gel, a conventional therapy used in the treatment of aks, in a prospective randomized clinical trial.33 sixty participants were enrolled in the study. two anatomically treatment areas were chosen in each patient and were randomized in a 1:1 ratio to receive either ntap twice weekly for three minutes or diclofenac 3% gel twice daily for three months. blinded assessment of number of lesions, surface area affected, olsen grading, local skin response score, and cosmetic outcome were compared at baseline, once per month skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 370 during treatment, and three-months posttreatment. at three-month follow-up, both treatment methods had significantly reduced total lesion count (ntap: 40%, ci 28-53%, diclofenac: 40%, 95% ci 27 – 52%) and affected surface area (ntap: 49%, 95% ci 37 – 61%, diclofenac: 36%, 95% ci 19 – 53%). ntap showed significantly better effectiveness in reducing lesion count (ntap: 33%, 95% ci 20 – 45%, diclofenac: 21%, 95% ci 9 – 33%) and ak-affected area (ntap: 41%, 95% ci 28 – 54%, diclofenac: 27%, 95% ci 13 – 42%) by the end of treatment. this study demonstrated that plasma is as good as a well-established modality for the treatment of aks. warts warts, also known as verruca vulgaris, are benign skin growths that are caused by the human papillomavirus (hpv). although harmless, these lesions can spread and cause symptoms, such as inflammation, pruritus, dermatitis, and scarring. standard of care (soc) treatment of warts involves cryotherapy, which may be poorly tolerated, especially in children. as such, there is a need for an efficacious and painless intervention for the treatment of warts. studies have shown that ntap leads to an influx of intracellular calcium, thereby inhibiting viral replication and promoting resolution of the wart.34 a 2020 case series involving five pediatric patients demonstrated that ntap is both safe and effective in the treatment of warts.34 all patients treated with ntap in the case series achieved complete clearance of their warts. patients found the treatment to be painless and equally efficacious, suggesting a potential advantage over cryotherapy in children. there were no adverse events reported, including blistering, scarring, significant pigmentary alteration, persistent nail changes, or pain. although promising, the clinical benefit and safety profile of ntap has yet not been extensively studied in pediatric patients with warts to date. future studies comparing the efficacy of ntap to cryotherapy in larger patient populations are required. wound healing wound healing is a natural process that is achieved by four-steps: hemostasis, inflammation, proliferation, and remodeling.35 impaired wound healing results from a disruption in the normal sequence, typically due to poor circulation, weakened immune system, diabetes, and/or the persistence of microbes. the antimicrobial properties of ntap have instigated both pre-clinical and clinical studies in wound healing utilizing the appj device. ntap has demonstrated in vitro and in vivo efficacy in pre-clinical models of wound healing.36 ntap promotes the release of transforming growth factor (tgf)-β1 cytokine from cells in vitro. tgf-β1 is a proinflammatory cytokine that promotes myofibroblast activation, which promotes extracellular matrix production and wound contraction.37 in a mouse model of diabetic ulceration, ntap treatment promoted cell proliferation, neovascularization, and regeneration of the epidermal layer, thus accelerating wound healing.36 ntap has demonstrated efficacy in over 20 pre-clinical studies, which are reviewed extensively elsewhere.38 a 2020 study investigated the efficacy of ntap in the treatment of diabetic foot ulcers.36 a total of 44 patients received standard care with or without ntap (n=22/group). treatment was applied three times per week for three weeks total. the ntap device used a noncontact probe and generated low temperature plasma using skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 371 helium gas. primary outcomes were wound size, number of cases reaching a wound size of less than 0.5 cm, and bacterial load reduction from baseline. results demonstrated a statistically significant reduction in wound size; a reduction in the fraction of wounds greater that 0.5 cm in size, and a reduction in bacterial load immediately preceding ntap treatment. it should be noted, however, that bacterial load only remained suppressed for ten hours. these data demonstrate a transient anti-microbial effect following ntap treatment and suggest the need for studies with more frequent application, particularly in an inpatient setting where repeat treatment exposure is feasible. a subsequent study assessed the efficacy of ntap in patients following once weekly treatment for eight weeks total.39 a total of 50 patients with diabetic pressure ulcers were split into two groups, consisting of soc versus soc plus ntap treatment. like the previous study, the ntap device utilized a noncontact probe and generated low temperature plasma using argon gas. patients that received ntap in addition to soc treatment had significantly improved pressure ulcer scale for healing (push) scores and a reduction in exudate following one week of treatment. wound size and push scores were significantly improved following the eightweek treatment course. these data, taken together, suggest the wound healing efficacy of ntap may not be restricted to antimicrobial activity. comparably, a 2020 study employed ntap once or twice weekly in patients with therapy-refractory chronic wounds.23 ntap significantly reduced wound size and bacterial load following 12week treatment. the results indicate that once weekly therapy is equally effective in comparison to twice or thrice weekly ntap. additionally, these data suggest chronic serial ntap administration can lead to sustained anti-microbial effects. the use of ntap therapy is rapidly expanding, particularly in the field of dermatology. a technology once used for medical sterilization has proven therapeutic in a wide variety of dermatological conditions.14 ntap has been extensively studied in wound healing applications in large patient populations and has proven efficacious, especially when co-administered with soc therapy. the use of ntap in onychomycosis, warts, and aks has been restricted to pilot studies. data from these studies are promising and should encourage future studies in larger patient populations. ntap has proven beneficial in reducing microbe count, promoting cell migration, healing, and in the destruction of aberrantly active cell populations. as such, we suggest ntap therapy deserves special consideration as an emerging pain-free and safe therapy in the treatment of dermatological conditions. conflict of interest disclosures: none funding: none corresponding author: chelsea shope, ba 96 jonathan lucas street suite 601, msc 617 charleston, sc email: shopec@musc.edu references: 1. kong m, kroesen j, morfill g, et al. plasma medicine: an introductory review. 2009. 2009;11. 2. dobrynin d, fridman g, friedman g, fridman a. physical and biological mechanisms of direct plasma interaction with living tissue. new journal of physics. 2009;11. 3. choi js, park i, lee sj, ju hj, lee h, kim j. serum procollagen type i n-terminal conclusion skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 372 propeptide and osteocalcin levels in korean children and adolescents. yonsei med j. 2019;60(12):1174-1180. 4. fluhr jw, sassning s, lademann o, et al. in vivo skin treatment with tissue-tolerable plasma influences skin physiology and antioxidant profile in human stratum corneum. exp dermatol. 2012;21(2):130-134. 5. lademann j, richter h, alborova a, et al. risk assessment of the application of a plasma jet in dermatology. j biomed opt. 2009;14(5):054025. 6. morfill g, kong m, zimmermann j. focus on plasma medicine. new journal of physics. 2009;11. 7. ermolaeva sa, petrov of, naroditsky bs, fortov ve, morfill ge, gintsburg al. 10.18 cold plasma therapy. in: brahme a, ed. comprehensive biomedical physics. oxford: elsevier; 2014:343-367. 8. choi jh, song ys, song k, lee hj, hong jw, kim gc. skin renewal activity of nonthermal plasma through the activation of beta-catenin in keratinocytes. sci rep. 2017;7(1):6146. 9. averett c, arora s, zubair h, singh s, bhardwaj a, singh ap. chapter nine molecular targets of honokiol: a promising phytochemical for effective cancer management. in: bathaie sz, tamanoi f, eds. the enzymes. vol 36. academic press; 2014:175-193. 10. schneider c, gebhardt l, arndt s, et al. cold atmospheric plasma causes a calcium influx in melanoma cells triggering cap-induced senescence. sci rep. 2018;8(1):10048. 11. miller v, lin a, fridman g. plasma stimulation of migration of macrophages. plasma process polym. 2014;11:1193 1997. 12. friedman pc, miller v, fridman g, lin a, fridman a. successful treatment of actinic keratoses using nonthermal atmospheric pressure plasma: a case series. j am acad dermatol. 2017;76(2):349-350. 13. bulson jm, liveris d, derkatch i, et al. nonthermal atmospheric plasma treatment of onychomycosis in an in vitro human nail model. mycoses. 2020;63(2):225-232. 14. fridman g, friedman g, gutsol a, shekhter a, vasilets v, fridman a. applied plasma medicine. plasma process polym. 2008;5:503-533. 15. nonsenko t, shimizu t, morfill g. designing plasmas for chronic wound disinfection. new journal of physics. 2009;11. 16. isbary g, morfill g, schmidt hu, et al. a first prospective randomized controlled trial to decrease bacterial load using cold atmospheric argon plasma on chronic wounds in patients. br j dermatol. 2010;163(1):78-82. 17. isbary g, heinlin j, shimizu t, et al. successful and safe use of 2 min cold atmospheric argon plasma in chronic wounds: results of a randomized controlled trial. br j dermatol. 2012;167(2):404-410. 18. daeschlein g, scholz s, ahmed r, et al. cold plasma is well-tolerated and does not disturb skin barrier or reduce skin moisture. j dtsch dermatol ges. 2012;10(7):509-515. 19. brehmer f, haenssle ha, daeschlein g, et al. alleviation of chronic venous leg ulcers with a hand-held dielectric barrier discharge plasma generator (plasmaderm(®) vu2010): results of a monocentric, two-armed, open, prospective, randomized and controlled trial (nct01415622). j eur acad dermatol venereol. 2015;29(1):148-155. 20. isbary g, koritzer j, mitra a, et al. ex vivo human skin experiments for the evaluation of safety of new cold atmospheric plasma devices. clin plasma med. 2013;1:36-44. 21. emmert s, brehmer f, hanble h, et al. atmospheric pressure plasma in dermatology: ulcus treatment and much more. clin plasma med. 2013;1:24-29. 22. lópez m, calvo t, prieto m, et al. a review on non-thermal atmospheric plasma for food preservation: mode of action, determinants of effectiveness, and applications. front microbiol. 2019;10:622. 23. moelleken m, jockenhofer f, wiegand c, buer j, benson s, dissemond j. pilot study on the influence of cold atmospheric plasma on bacterial contamination and healing tendency of chronic wounds. j dtsch dermatol ges. 2020;18(10):1094-1101. 24. lipner sr fg, scher rk. pilot study to evaluate a plasma device for the treatment of onychomycosis. clin exp dermatol. 2017;42(3):295-298. 25. friedman pc. cold atmospheric pressure (physical) plasma in dermatology: where are we today? int j dermatol. 2020;59(10):11711184. 26. westerberg dp, voyack mj. onychomycosis: current trends in diagnosis and treatment. am fam physician. 2013;88(11):762-770. 27. foley k, gupta ak, versteeg s, mays r, villanueva e, john d. topical and deviceskin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 373 based treatments for fungal infections of the toenails. cochrane database syst rev. 2020;1:cd012093. 28. beck tc, beck kr, morningstar j, benjamin mm, norris ra. descriptors of cytochrome inhibitors and useful machine learning based methods for the design of safer drugs. pharmaceuticals (basel). 2021;14(5). 29. lin a, truong, b., pappas, a., kirifides, l., oubarri, a., chen, s., lin, s., dobrynin, d., fridman, g., fridman, a., sang, n. and miller, v. uniform nanosecond pulsed dielectric barrier discharge plasma enhances anti-tumor effects by induction of immunogenic cell death in tumors and stimulation of macrophages. plasma process polym. 2015;12:1392-1399. 30. fridman g, peddinghaus, m., balasubramanian, m. et al. . blood coagulation and living tissue sterilization by floating-electrode dielectric barrier discharge in air. plasma chem plasma process. 2006;26:425–442. 31. wirtz m, stoffels i, dissemond j, schadendorf d, roesch a. actinic keratoses treated with cold atmospheric plasma. j eur acad dermatol venereol. 2018;32(1):e37e39. 32. arisi m, soglia s, guasco pisani e, et al. cold atmospheric plasma (cap) for the treatment of actinic keratosis and skin field cancerization: clinical and high-frequency ultrasound evaluation. dermatol ther (heidelb). 2021;11(3):855-866. 33. koch f, salva ka, wirtz m, et al. efficacy of cold atmospheric plasma vs. diclofenac 3% gel in patients with actinic keratoses: a prospective, randomized and rater-blinded study (acticap). j eur acad dermatol venereol. 2020;34(12):e844-e846. 34. friedman pc, fridman g, fridman a. using cold plasma to treat warts in children: a case series. pediatr dermatol. 2020;37(4):706709. 35. guo s, dipietro la. factors affecting wound healing. j dent res. 2010;89(3):219-229. 36. mirpour s, fathollah s, mansouri p, et al. cold atmospheric plasma as an effective method to treat diabetic foot ulcers: a randomized clinical trial. sci rep. 2020;10(1):10440. 37. ko uh, choi j, choung j, moon s, shin jh. physicochemically tuned myofibroblasts for wound healing strategy. sci rep. 2019;9(1):16070. 38. dubey sk ps, alexander a, agrawal m, achalla vpk, pal un , pandey mm, kesharwani p. cold atmospheric plasma therapy in wound healing. process biochemistry. 2022;112:112-123. 39. chuangsuwanich a, assadamongkol t, boonyawan d. the healing effect of lowtemperature atmospheric-pressure plasma in pressure ulcer: a randomized controlled trial. int j low extrem wounds. 2016;15(4):313-319. evidence review of the prognostic 40-gene expression profile test for cutaneous squamous cell carcinoma methods disclosures references › this study was sponsored by castle biosciences, inc. › all authors are employees and shareholders of castle biosciences, inc. 1. jambusaria-pahlajani, et al. arch derm 2010 2. farberg, et al. dermatol clinics 2017 3. colomer et al. clin transl oncol 2018 4. plasseraud et al. j oncol. 2016 5. teplitz, et al jdd 2019 6. litchman, et al cmro 2020 7. farberg, et al. in preparation 8. wysong et al., jaad 2021 9. ibrahim, et al future oncology 2021 10. borman et al. diagn pathol under review 11. farberg et al. cmro 2020 12. aaron et al. jdd 2021 presented at winter clinical dermatology conference; january 14-19, 2022. matthew s. goldberg1, sarah j. kurley1, jennifer j. siegel1, alison l. fitzgerald1, robert w. cook1 1castle biosciences, inc. for more information: mgoldberg@castlebiosciences.com objective › to describe the performance of the 40-gep test as a method of accurate assessment of a patient’s risk for metastasis after diagnosis of cscc with one or more risk factors. ›the data across the three critical pillars of molecular testing demonstrate the robustness, accuracy and utility of the 40-gep test. ›clinical utility data illustrates that physicians understand 40-gep test results and how to appropriately integrate these results into their clinical considerations for treatment of cscc patients with one or more risk factors, ideally leading to a more personalized treatment pathway. ›clinical validity data supports the use of the test as an adjunct to current risk assessment to better evaluate a patient’s metastatic risk. ›analytical validity data exhibited robust technical reliability of the 40-gep on clinical samples along with high concordance rates across multiple performance experiments. conclusions › previously published and unpublished clinical utility data addressing the impact of the 40-gep on patient management plans were summarized.5-7 › previously published clinical validation data from independent cases with verified clinicopathologic information and known outcomes were assessed by kaplan-meier survival analysis and cox regression analysis.8,9 › analytical validation of the performance of the 40-gep test included precision experiments to assess inter-assay and intraassay reliability and the assessment of its technical success rate.10 synopsis › high-risk cutaneous squamous cell carcinoma (cscc) is a subset of cscc commonly requiring a more aggressive treatment regimen, due to an increased probability of recurrence, nodal/distant metastasis, or disease specific death. › guidelines and staging criteria for cscc are overall vague, creating a burden for clinicians when establishing an appropriate treatment plan. 1 › in many cancer types, molecular prognostics have had a significant and appropriate impact in patient care.2,3,4 › the purpose for the development of the prognostic 40-gep test was to identify high-risk cscc early in the disease state, such that its result could complement current risk assessment methods for development of more personalized management plans to reduce the risk of poor outcomes for cscc patients. results › three separate clinical impact surveys were distributed to dermatologic clinicians (n=598).5-7 table 1 presents the results of physician responses to “no 40-gep” and post-40-gep test results regarding management changes. responses for all surveys demonstrated that the prognostic information garnered through the 40-gep could aid in cscc patient management in a risk appropriate manner. a representative patient vignette highlights that 97.5% of clinicians would change patient management intensity recommendations based on the 40-gep with reduced intensity for class 1 and increased intensity for class 2b post-test management decisions (figure 1). › figure 2 demonstrates the ability of the 40-gep test to classify patients based on risk of metastasis.8,9 › regardless of the specific risk factor or clinicopathologic risk assessment method included in the multivariable regression analysis, the 40-gep demonstrated independent and statistically significant prognostic value with hazard ratios (hr) for class 2a and 2b similar to or beyond that of clinicopathologic factor-based systems. (table 2). › reliability of the 40-gep test for class call assignments was verified by interand intra-assay concordance of 93% (n=27/29) and 98% (n=45/46), respectively.10 over the duration of one year, 98% of all clinically tested samples with sufficient tumor content gave actionable class call outcomes, highlighting the low multi-gene failure rate of the test. (table 3).10 figure 2. the 40-gep accurately classifies patients by metastatic risk figure 1. example of 40-gep impact on overall management strategy intensity6 multivariate cox regression risk factor n hazard ratio p value 40-gep result class 1 212 1.00 --class 2a 185 2.33 0.013 class 2b 23 6.86 <0.001 clinicopathologic risk factors poor differentiation 58 2.29 0.011 perineural invasion 53 1.22 ns deep invasion 72 2.05 0.039 tumor diameter n/a 1.07 ns 40-gep result class 1 212 1.00 --class 2a 185 2.92 <0.001 class 2b 23 9.50 <0.001 nccn risk group high 255 1.00 --very high 165 1.99 0.009 table 2. the 40-gep provides independent prognostic value to existing risk assessment methods cases were comprehensively staged based on medical records, pathology reports, and definitive surgical reports. all cases were high-risk by nccn guidelines for localized cscc or met mohs micrographic surgery appropriate use criteria. scan here for more info analytic validity10clinical validity9 clinical utility5-7 multivariate cox regression risk factor n hazard ratio p value 40-gep result class 1 212 1.00 --class 2a 185 2.97 <0.001 class 2b 23 11.4 <0.001 ajcc8 t stage t1/t2 340 1.00 --t3/t4 80 2.69 <0.001 40-gep result class 1 212 1.00 --class 2a 185 2.98 <0.001 class 2b 23 9.42 <0.001 bwh t stage t1/t2a 364 1.00 --t2b/t3 56 2.38 0.002 intra-assay concordance 98% inter-assay concordance 93% sample longevity and stability 96% overall technical success 98% table 3. the 40-gep shows robust repeatability and reproducibility10 clinical impact studies of 40-gep5-7 clinicians patients specific clinical recommendation changed with 40-gep overall change in management plan recommended with 40-gep 34 real-world test users 6 real-world cases f/u, slnb, baseline nodal imaging, adjuvant radiation, adjuvant chemotherapy, surveillance imaging integration of the 40-gep class call significantly impacted recommended patient management plans in a riskappropriate manner while staying within guidelines. 162 dermatologists* 2 patient vignettes f/u, slnb, nodal imaging, adjuvant radiation, adjuvant chemotherapy 402 dermatologists 3 patient vignettes f/u, slnb referral, radiation, chemotherapy, immunotherapy f/u = follow up schedule; slnb = sentinel lymph node biology; *majority dermatologists with 8.6% dermatology np/pa, 1.2% dermatopathologist, 1.9% other table 1. 40-gep testing consistently changes management recommendations across 3 clinical impact studies 67-year-old male 1.2 cm scalp lesion with poor differentiation, 1.2 mm depth (2 high-risk clinicopathologic factors) nccn high-risk cscc ・ ajcc t1 ・ bwh t2a (adapted from litchman et al.) publications on proposed incorporation of 40-gep testing: › cross-specialty expert panel reports decision-making points where 40-gep testing could inform clinical management12 › proposed risk-aligned incorporation of 40-gep testing into management strategies within nccn guidelines11 the vast majority of clinicians would change management intensity for this patient based on the 40-gep class result reduced clinical management intensity increased clinical management intensity 40-gep impact by clinician class 2a 97.5% 59.9% class 2b 93.2% class 1 59.9% 45.1% overall change overall change neutral increase neutral decrease (adapted from ibrahim et al.) https://castlebiosciences.com/research-development/publications/ tapinarof cream 1% once daily for plaque psoriasis: efficacy by baseline disease characteristics and demographics in two pivotal phase 3 trials leon kircik,1,2 linda stein gold,3 james del rosso,4 seemal r. desai,5,6 brad p. glick,7 howard sofen,8 anna m. tallman,9 david s. rubenstein,9 philip m. brown9 1skin sciences pllc, louisville, ky, usa; 2icahn school of medicine at mount sinai, new york, ny, usa; 3henry ford health system, detroit, mi, usa; 4jdr dermatology research/thomas dermatology, las vegas, nv, usa; 5university of texas southwestern medical center, dallas, tx, usa; 6innovative dermatology, plano, tx, usa; 7herbert wertheim college of medicine, florida international university, miami, fl, usa; 8david geffen ucla school of medicine, los angeles, ca, usa; 9dermavant sciences, inc., morrisville, nc, usa synopsis ■ tapinarof is a first-in-class, non-steroidal, topical therapeutic aryl hydrocarbon receptor modulating agent (tama) in development for the treatment of psoriasis and atopic dermatitis ■ in two identical, randomized, double-blind phase 3 trials, psoaring 1 and psoaring 2, tapinarof cream 1% once daily (qd) demonstrated highly statistically significant efficacy versus vehicle at 12 weeks and was well tolerated in adults with mild to severe plaque psoriasis1 objective ■ to present results for the pivotal phase 3 primary efficacy endpoint (proportion of patients who achieved a physician global assessment [pga] response at week 12) by baseline disease characteristics and demographics using pooled data from psoaring 1 and psoaring 2 methods study design ■ patients with mild to severe plaque psoriasis were randomly assigned 2:1 to receive tapinarof cream 1% qd or vehicle qd for 12 weeks in two identical, phase 3, multicenter (us and canada), double-blind, vehicle-controlled trials (figure 1) ■ following the double-blind period, patients could enroll in a separate open-label, long-term extension study for an additional 40 weeks of treatment, or complete a follow-up visit 4 weeks after the end of treatment (week 16) figure 1. study design *pga of 2 (mild) or 4 (severe) was limited to ~10% each of the total randomized population; ~80% of the randomized population had a pga of 3 (moderate). bsa, body surface area; pga, physician global assessment; qd, once daily; r, randomized. endpoints and statistical analysis ■ the primary endpoint was pga response at week 12, defined as the proportion of patients with a pga score of clear (0) or almost clear (1) and ≥2-grade improvement in pga score from baseline to week 12 ■ the incidence, frequency, and nature of adverse events (aes) and serious aes were monitored from the start of study treatment until the end-of-study visit ■ the pooled analyses used multiple imputation for the intention-to-treat (itt) populations in psoaring 1 and 2 ■ tapinarof cream 1% qd and vehicle groups were compared within each subgroup for the primary endpoint using 95% confidence intervals for the relative risk calculated using cochran-mantel-haenszel analyses stratified by baseline pga score results patient disposition and baseline characteristics ■ the pooled analysis population included 1025 patients randomized to tapinarof cream 1% qd (n=683) or vehicle qd (n=342) in psoaring 1 and 2 (itt population) ■ baseline disease characteristics and demographics in the pooled population were comparable across treatment groups (table 1) ■ overall, at baseline, 82% had a pga score of 3 (moderate), 57% had psoriasis for >10 years, and 26% had ≥10% body surface area (bsa) affected table 1. baseline patient demographics and disease characteristics (pooled psoaring 1 and 2) tapinarof 1% qd (n=683) vehicle qd (n=342) age <65 years, n (%) 584 (85.5) 302 (88.3) male, n (%) 401 (58.7) 188 (55.0) race, n (%) caucasian 586 (85.8) 284 (83.0) asian 46 (6.7) 25 (7.3) black/african american 30 (4.4) 17 (5.0) american indian or alaska native 2 (0.3) 2 (0.6) native hawaiian or other pacific islander 1 (0.1) 1 (0.3) other* 13 (1.9) 10 (2.9) country of enrollment, n (%) us 514 (75.3) 262 (76.6) canada 169 (24.7) 80 (23.4) pga, n (%) 2 – mild 67 (9.8) 36 (10.5) 3 – moderate 559 (81.8) 277 (81.0) 4 – severe 57 (8.3) 29 (8.5) bsa affected, n (%) <10% 505 (73.9) 257 (75.1) ≥10% 178 (26.1) 85 (24.9) duration of disease, n (%) <5 years 154 (22.5) 73 (21.3) 5-10 years 128 (18.7) 89 (26.0) >10 years 401 (58.7) 180 (52.6) *includes patients with multiple races reported. itt population. bsa, body surface area; itt, intention-to-treat; pga, physician global assessment; qd, once daily. pga response by baseline disease characteristics and demographics ■ the primary endpoint (pga of 0 or 1 and ≥2-grade improvement at week 12) was met; pga response rates were highly statistically significant in the tapinarof cream 1% qd group versus the vehicle group in both psoaring 1 and 2: 35.4% vs 6.0% (p<0.0001) and 40.2% vs 6.3% (p<0.0001), respectively1 ■ the efficacy of tapinarof 1% qd was consistent across subgroups, regardless of baseline disease characteristics such as pga score, %bsa affected, and duration of disease, and demographics such as sex, age, race, country of enrollment (figure 2) ■ notably, based upon the definition of pga response requiring achievement of pga=0 or 1 with ≥2-grade improvement, mild subjects had to achieve complete disease clearance (pga=0) and severe subjects had to improve a minimum of 3 points, to be responders figure 2. pga response at week 12 by baseline disease characteristics (a) and demographics (b) (pooled psoaring 1 and 2) *lower limit of the 95% ci for the relative risk >1, indicating a significantly higher probability of pga response with tapinarof compared with vehicle. relative risk and associated 95% cis were calculated using cochran-mantel-haenszel analyses, stratified by baseline pga score. relative risk indicates the probability of pga response occurring in the tapinarof group versus the probability of pga response occurring in the vehicle group. †non-caucasian category includes asian, black/african american, american indian or alaska native, native hawaiian, or other pacific islander, and other and has been grouped due to small patient numbers. itt, mi. mean proportion (se). pga response defined as a pga score of clear (0) or almost clear (1) with ≥2-grade improvement from baseline. ci, confidence interval; itt, intention-to-treat; mi, multiple imputation; pga, physician global assessment; qd, once daily; se, standard error. safety ■ treatment-emergent aes (teaes) were mostly mild to moderate in severity ■ the most common teaes overall were folliculitis (20.2% tapinarof vs 0.9% vehicle), nasopharyngitis (5.7% tapinarof vs 4.4% vehicle), and contact dermatitis (4.8% tapinarof vs 0.3% vehicle) ■ although conclusions cannot be drawn due to the small number of patients in some subgroups, the frequency and type of aes appeared to be generally comparable across subgroups and consistent with those observed in the overall population conclusions ■ tapinarof cream 1% qd was consistently efficacious and well tolerated irrespective of baseline pga score, bsa affected, duration of psoriasis, sex, age, race, or country of enrollment (us or canada) ■ due to the small number of patients in some subgroups, limitations exist regarding the ability to draw definitive conclusions from the subgroup analysis ■ the consistent efficacy and tolerability in all subgroups support the potential use of tapinarof cream 1% qd across a broad spectrum of disease severity and patient demographics ■ a long-term extension trial (psoaring 3) of intermittent treatment with tapinarof 1% qd based on pga score demonstrated continued efficacy following the 12-week pivotal trials and an ~4-month remittive effect off therapy2 ■ tapinarof cream 1% qd has potential to be the first topical psoriasis treatment with a novel mechanism of action in almost 20 years references 1. lebwohl m, et al. skin. 2020;4(6):s75. https://doi.org/10.25251/skin.4.supp.75; 2. strober b, et al. innovations in dermatology virtual spring conference 2021, poster presentation, march 16–20, 2021. acknowledgments this study was funded by dermavant sciences, inc. the authors thank the participating investigators, patients and their families, and colleagues involved in the conduct of the study. l.k. has served as a consultant/speaker/investigator/ advisory board member for abbott laboratories, abbvie, ablynx, aclaris, acambis, allergan, inc., almirall, amgen, inc., anacor pharmaceuticals, anaptys, arcutis, arena, assos pharma, astellas pharma us, inc., asubio, bausch health, berlex laboratories (bayer healthcare pharmaceuticals), biogen-idec, biolife, biopelle, bms, boehringer-ingleheim, breckinridge pharma, cassiopea, centocor, inc., cellceutix, cipher, coherus, colbar, combinatrix, connetics corporation, coria, dermavant sciences, inc., dermira, dermik laboratories, dow pharmaceutical sciences, inc., dr. reddy’s lab, dusa, embil pharmaceuticals, eli lilly, eos, exeltis, ferndale laboratories, inc., foamix, ferrer, galderma, genentech, inc., glaxosmithkline, plc, glenmark, health point, ltd, idera, incyte, intendis, innocutis, innovail, isdin, johnson & johnson, kyowakirin, laboratory skin care, inc., leo pharma, l’oreal, 3m, maruho, medical international technologies, merck, medicis pharmaceutical corp., merz, nano bio, novartis ag, noven pharmaceuticals, nucryst pharmaceuticals corp, obagi, onset, orthoneutrogena, pediapharma, pfizer, promius, puracap, pharmaderm, qlt, inc, quinnova, quatrix, regeneron, sanofi, serono (merck serono international sa), skinmedica, inc., stiefel laboratories, inc., sun pharma, taro, tolerrx, triax, ucb, valeant pharmaceuticals intl, warner-chilcott, xenoport, zage. l.s.g has served as a consultant, and/or has received payment for the development of educational presentations, and/or has received grants from arcutis, amgen, bristol myers squibb, dermavant sciences, inc., eli lilly, leo pharma, ortho dermatologic, and ucb biopharma. j.d.r is an advisor and research investigator for dermavant sciences, inc. b.p.g. has served as an investigator/speaker/advisor for abbvie, brickell biotech, celgene, chemocentryx, corrona registry pso, corrona registry ad, dermavant sciences, inc, dermira, eli lilly, janssen, novartis, ortho dermatologics, pfizer, prose registry, regeneron, sanofi-genzyme, sun pharmaceutical industries, inc. h.s. has served as scientific adviser and/or clinical study investigator for abbvie, boehringer ingelheim, bristol myers squibb, dermavant, sciences inc., eli lilly, incyte, janssen, leo pharma, novartis, pfizer, sanofi-genzyme, sun pharma, ucb. a.m.t, d.s.r and p.m.b. are employees of dermavant sciences, inc., with stock options. editorial and medical writing support under the guidance of the authors was provided by apothecom, uk, and was funded by dermavant sciences, inc. in accordance with good publication practice (gpp3) guidelines (ann intern med. 2015;163:461–464). contact dr leon kircik at wedoderm@yahoo.com with questions or comments. adult patients with plaque psoriasis • aged 18–75 years old • pga score ≥2* • bsa ≥3%–≤20% double-blind treatment (12 weeks) 2:1 2:1 tapinarof 1% qd (n=340) tapinarof 1% qd (n=343) vehicle qd (n=170) vehicle qd (n=172) (n=510) (n=515) r r p ro p o rt io n o f p at ie n ts , % 19.9% 5.8% 0% 2 (mild) 3 (moderate) 4 (severe) <10% ≥10% <5 years 5−10 years >10 years baseline pga bsa affected duration of disease 40.1% * 6.4% 36.3% * 4.7% 38.6% * 5.1% 35.6% * 9.3% 34.8% * 7.8% 36.9% * 4.1% 39.3% * 6.5%10% 20% 30% 40% tapinarof 1% qd vehicle qd 50% 60%(a) p ro p o rt io n o f p at ie n ts , % 0% 10% 20% 30% 40% 50% 60%(b) sex 38.5% 5.3% male * female 36.9% 7.2% * age <65 years 36.4% 5.7% * ≥65 years 46.1% * 9.6% race (binary)† caucasian * 38.8% 6.4% noncaucasian * 30.5% 5.3% country of enrollment us * 36.1% 6.0% canada * 42.9% 6.5% tapinarof 1% qd vehicle qd acknowledgements: medical writing support was provided by prescott medical communications group (chicago, il) with financial support from ortho dermatologics; ortho dermatologics is a division of bausch health us, llc • presented at 2021 fall clinical dermatology conference for pas & nps • november 12-14, 2021 • orlando, fl synopsis � acne prevalence may be higher in obese individuals, potentially due to hormonal, inflammatory, and/or dietary factors.1,2 � however, the effect of obesity on the efficacy and safety of topical acne treatments is largely unknown � the growing population of obese individuals in the united states, along with the negative impact of high body mass index (bmi) and acne on health-related quality of life, underscores the need to identify appropriate acne therapies in this population3-5 � a new, lower-dose tazarotene 0.045% lotion formulation (arazlo®, ortho dermatologics) was developed utilizing polymeric emulsion technology • this easily spreadable lotion formulation allows for more efficient delivery of tazarotene into dermal layers while reducing potential skin irritation objective � to evaluate efficacy, safety, and impact on quality of life of tazarotene 0.045% lotion in obese and morbidly obese individuals with acne methods � in two identical phase 3 randomized, double-blind, vehicle-controlled studies (nct03168321 and nct03168334), participants aged ≥9 years with moderate-to-severe acne (evaluator’s global severity score [egss] of 3 or 4) were randomized (1:1) to oncedaily tazarotene 0.045% lotion or vehicle lotion for 12 weeks • in these studies, cerave® hydrating cleanser and cerave® moisturizing lotion (l’oreal, ny) were provided as needed for optimal moisturization/ cleaning of the skin � outcomes comprised reductions in inflammatory and noninflammatory lesion counts, treatment success (proportion of participants achieving ≥2-grade reduction from baseline in egss and score of 0 [clear] or 1 [almost clear]), and acne-specific quality of life (acne-qol) questionnaire � cutaneous safety and tolerability were also evaluated � pooled data at week 12 were analyzed for the bmi subgroup ≥30 kg/m2 (obese and morbidly obese) safety � mean cutaneous safety and tolerability scores were low for both tazarotene 0.045% lotion and vehicle lotion (scored from 0=none to 3=severe; figure 3) • with both tazarotene and vehicle, mean scores at baseline and week 12 were ≤0.2 for scaling, hypopigmentation, itching, burning, and stinging • slight improvements at week 12 versus baseline were observed for erythema, hypopigmentation, and hyperpigmentation with tazarotene • results were similar to the overall population6 (data not shown) figure 2. acne-qol improvements at week 12 in participants with bmi ≥30 kg/m2 (itt population, pooled) 12 0 4 8 m e a n c h a n g e f ro m b a se lin e t o w e e k 1 2 acne-qol domains vehicle lotion taz 0.045% lotion selfperception 7.7 9.3 145132 roleemotional 6.96.8 145132 rolesocial 5.45.8 144132 acne symptoms 6.2 7.0 145132 im p ro ve m e n t n= higher scores for each domain in acne-qol reflect increased health-related quality of life. self-perception, role-emotional, and acne symptoms domain score ranges are 0 to 30; role-social domain score range is 0 to 24; a positive mean change indicates a favorable result. overall population mean change from baseline to week 12 for taz (n=690) vs vehicle (n=723 [n=722 for role-social]): self-perception, 7.5 vs 6.7; role-emotional, 6.0 vs 5.5; role-social, 4.7 vs 4.1; acne symptoms, 6.4 vs 5.3.7 acne-qol, acne-specific quality of life; bmi, body mass index; itt, intent to treat; taz, tazarotene 0.045% lotion. figure 3. mean cutaneous safety and tolerability scores in participants with bmi ≥30 kg/m2 (safety population, pooled) 3 0 1 2 m e a n s co re ( + s d ) scaling severe moderate mild erythema hypopigmentation hyperpigmentation itching burning stinging taz baseline vehicle baseline taz week 12 vehicle week 12 n values were as follows: taz baseline n=153, taz week 12 n=133, vehicle baseline n=162, vehicle week 12 n=145. bmi, body mass index; sd, standard deviation; taz, tazarotene 0.045% lotion. treating acne in obese and morbidly obese patients with tazarotene 0.045% lotion: post hoc analysis of pooled phase 3 data jonette keri, md, phd1; leon h kircik, md2,3,4; lawrence green, md5; glynis ablon, md6; william philip werschler, md7; emil a tanghetti, md8; zoe d draelos, md9; eric guenin, pharmd, phd, mph10 1university of miami, miller school of medicine, miami, fl; 2indiana university school of medicine, indianapolis, in, 3physicians skin care, pllc, louisville, ky, 4icahn school of medicine at mount sinai, new york, ny; 5george washington university school of medicine, washington, dc; 6ablon skin institute & research center, manhattan beach, ca; 7university of washington school of medicine, seattle, wa; 8center for dermatology and laser surgery, sacramento, ca; 9dermatology consulting services, pllc, high point, nc; 10ortho dermatologics,* bridgewater, nj *ortho dermatologics is a division of bausch health us, llc results participants � a total of 332 participants with bmi ≥30 kg/m2 were included for analysis • of these, one-fifth (n=70) were morbidly obese (bmi ≥40 kg/m2) � the bmi ≥30 kg/m2 subgroup, compared to the overall pooled population (n=16146), had more participants who were female (79.5% vs 65.9%), black (23.8% vs 16.2%), older (mean age: 23.1 vs 20.5 years), and had an egss score of 3 (93.1% vs 90.9%) efficacy � tazarotene-treated obese and morbidly obese participants had an approximately 55% reduction in both inflammatory and noninflammatory lesions following 12 weeks of treatment (figure 1) • results were comparable to reductions seen in the overall population (57.9% and 56.0% reduction, respectively)6 � at week 12, just over one-third of participants treated with tazarotene 0.045% lotion achieved treatment success (bmi ≥30 kg/m2 taz vs vehicle: 33.5% vs 21.9%; p<0.05), similar to the overall population (30.4% vs 17.9%; p<0.001)6 figure 1. lesion reduc tions in participants with bmi ≥30 kg/m2 (itt population, pooled) in�ammatory lesions -34.4% -43.3% -52.6% -34.7% -48.5% -56.8% -70% -60% -50% -40% -30% -20% -10% 0% baseline week 4 week 8 week 12 vehicle lotion (n=172) taz 0.045% lotion (n=160) ls m e a n p e rc e n t c h a n g e f ro m b a se lin e nonin�ammatory lesions -28.3% -38.1% -45.9% -35.9% -46.3% -54.6% -70% -60% -50% -40% -30% -20% -10% 0% baseline week 4 week 8 week 12 vehicle lotion (n=172) taz 0.045% lotion (n=160) ** ** * *p<0.05 vs vehicle; **p=0.01 vs vehicle. overall population ls mean percent reductions from baseline to week 12 for taz (n=799) vs vehicle (n=815): inflammatory lesions, -57.9% vs -47.8% (p<0.001); noninflammatory lesions, -56.0% vs -42.0% (p<0.001).6 bmi, body mass index; itt, intent to treat; ls, least squares; taz, tazarotene 0.045% lotion. quality of life � acne-qol domain scores improved from baseline to week 12 in obese and morbidly obese participants, with the greatest improvements observed in the acne-qol domains of “self-perception” and “acne symptoms” (figure 2) • improvements across all four acne-qol domains following tazarotene treatment were more substantial in obese and morbidly obese participants than the overall population7 conclusions � in obese and morbidly obese participants with moderate-to-severe acne, tazarotene 0.045% lotion reduced inflammatory and noninflammatory lesions by over half, with one-third of participants achieving clear/ almost clear skin � quality of life improvements with tazarotene 0.045% lotion were substantially greater in obese and morbidly obese participants versus the overall study population7 • these results may be due to both the worse qol at baseline (data not shown) and the higher percentage of females in the ≥30 kg/m2 group compared with the overall population • studies have shown that females with acne are more likely to develop anxiety/ depression, and improvements in acne positively affect quality of life8; furthermore, females have been shown to have relatively greater quality of life improvements with tazarotene 0.045% lotion than males7 � cutaneous safety and tolerability scores with tazarotene lotion were generally similar between baseline and week 12 � tazarotene 0.045% lotion was efficacious and well tolerated in obese and morbidly obese individuals with acne, and led to large improvements in the quality of life of these participants • these results are notable given the limited clinical data of acne treatments in this growing population references 1. heng ahs, chew ft. sci rep. 2020;10(1):5754. 2. dreno b. jeadv. 2017;31(5):8-12. 3. k yang l, colditz ga. jama intern med. 2015;175(8):1412-3. 4. kolotkin rl, meter k, williams gr. obes rev. 2001;2(4):219-229. 5. gieler u, gieler t, kupfer jp. j eur acad dermatol venereol. 2015;29 suppl 4:12-14. 6. tanghetti ea, werschler wp, lain e, et al. j drugs dermatol. 2020;19(3):272-279. 7. kircik lh, lain e, gold m, et al. j drugs dermatol. 2020;19(11):1086-1092. 8. skroza n, tolino e, proietti i, et al. g ital dermatol venereol. 2016;151(1):87-92. author disclosures jonette keri has served on speaker’s bureau for vyne therapeutics. leon kircik has acted as an investigator, advisor, speaker, and consultant for ortho dermatologics. lawrence green has served as investigator, consultant, or speaker for almirall, cassiopea, galderma, ortho dermatologics, sol gel, sun pharma, and vyne. glynis ablon has served as a consultant and advisory board member for galderma, sinclair, thermi-almirall, erchonia, sunetics, nutrafol, and lifes2good. william philip werschler has served as an investigator for ortho dermatologics. emil tanghetti has served as speaker for novartis, ortho dermatologics, sun pharma, lilly, galderma, abbvie, and dermira; served as a consultant/clinical studies for hologic, ortho dermatologics, and galderma; and is a stockholder for accure. zoe draelos received funding from ortho dermatologics to conduct the research presented in this poster. eric guenin is an employee of ortho dermatologics and may hold stock and/or stock options in its parent company. skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 437 brief article turning down the fire: the role of botulinum toxin microdroplets in refractory rosacea erythema arash babadjouni, ms,1 celine h. phong, bs,1 jodie raffi, md,1 natasha a. mesinkovska, md, phd1 1 university of california, irvine, department of dermatology, irvine ca growing interest and use of botulinum neuromodulators in the battle against skin aging has led to the discovery of several novel, off-label uses. after years of proven efficacy and safety, anecdotal reports of improved facial flushing, erythema and inflammation are emerging following botulinum toxin a (btx-a) treatment for cosmetic rejuvenation. dilute, intradermal btx-a (microdroplet btx-a) can improve facial erythema and skin quality, as denoted by reduced sebum production and facial pores. several studies and case reports have reported clinical improvement in flushing, erythema, and facial rejuvenation after treatment with btx-a.1 we present a case of refractory papulo-pustular rosacea in which intradermal microdroplet btx-a injections were successfully used to control erythema. abstract introduction: dermal “micro-injections" of botulinum toxin a (btx-a) treatment can improve facial flushing and erythema in patients with refractory rosacea. we present a case of a patient with longstanding papulo-pustular rosacea with flushing, refractory to laser, topical and systemic therapies, where intradermal microdroplet btx-a injections successfully controlled erythema and flushing. case description: a 49-year-old white female with a 4-year history of refractory papulo-pustular rosacea presented with bright, central facial erythema and telangiectasias after failing multiple 595 nm pulsed dye laser, topical (azelaic acid 15% gel, 0.025% tretinoin cream, and metronidazole cream 0.75%) and systemic (isotretinoin 20 mg daily, spironolactone 25 mg daily and doxycycline 100 mg twice daily for 14 days) treatments. at treatment 1, 20 u of btx-a was injected intradermally (0.05 ml of 1.25 iu/0.1 ml per microdroplet) to the erythematous lesions. treatment 2 was performed at her 4week follow-up where we administered 15 u of btx-a intradermally (0.05 ml of 1.25 iu/0.1 ml per microdroplet). the patient was seen 4, 8, and 16 weeks after her second treatment where no btx-a was administered due to a significant reduction in erythema and lasting results. discussion: significant clinical improvement and patient satisfaction were achieved. no adverse events were reported after treatment aside from mild, localized injection site pain during the procedure. btx-a administered as intradermal microdroplet injects can be a safe and efficacious option in the treatment of refractory rosacea erythema. microbotox may be an effective adjunct, especially when topical and systemic therapies have failed. introduction case description skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 438 a 49-year-old white, non-hispanic female with a 4-year history of refractory papulopustular rosacea presented to our tertiary care dermatology clinic with bright, central facial erythema and telangiectasias after failing multiple laser treatments, topical therapies, and systemic medications. episodes of facial erythema and flushing were provoked by heat, exercise, sun exposure, and spicy foods. her past medical history included complex regional pain syndrome, breast cancer (taking tamoxifen), hormonal acne, and a positive antinuclear antibody test. she had previously failed extensive treatment, including nine treatments of pulsed dye laser (595 nm) over the past three years. energy densities ranging from 6 to 6.5 j/cm2, pulse durations from 3-6 ms using the 7or 10-mm hand piece, and total pulses ranging from 53-153 were tried. additionally, several topicals (azelaic acid 15% gel, 0.025% tretinoin cream, and metronidazole cream 0.75%) and systemic therapies (isotretinoin 20 mg daily, spironolactone 25 mg daily, and doxycycline 100 mg twice daily) were trialed with minimal, inconsistent improvement. the patient received a total of 35 u of intradermal microdroplet btx-a over two treatments. botulinum toxin a (allergan, campbell, calif., usa) was reconstituted with sterile saline to achieve the desired concentration. the microdroplet btx-a dilution used was chosen in reference to a previous study.2 at treatment 1, 20 u of btx-a was injected intradermally at 5 mm intervals (0.05 ml of 1.25 iu/0.1 ml per microdroplet) to erythematous lesions at the glabella, cheek, nose and chin using a 30guage syringe (fig 1). isotretinoin 20 mg daily was concomitantly started at treatment 1. after 4 weeks, her condition improvement significantly with some persistent flushing and no change in facial movements or animations. treatment 2 was performed at her 4-week follow-up when we administered 15 u of btx-a at the same dilutions, and intervals, and sites. the patient was seen in follow up 4, 8, and 16 weeks after her second treatment. no btx-a was administered due to a significant reduction in erythema and lasting results. no adverse events were reported after treatment aside from mild, localized pain at the injection site during the procedure. figure 1. 49-year-old female with refractory papulo-pustular rosacea erythema (a) before receiving intradermal microdroplet btx-a injections for facial erythema and flushing (b) 4 weeks after treatment 1 with 20 u of btx-a (0.05 ml of 1.25 iu/0.1 ml per microdroplet) injected at 5 mm intervals to erythematous lesions on the glabella, cheek, nose, and chin (c) 4 weeks after treatment 2 receiving 15 u btx-a at the same dilutions, intervals, and sites. discussion skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 439 rosacea, a common, chronic inflammatory skin condition, can present with varying clinical symptoms depending on disease classification and stage. patients may suffer from intermittent or persistent erythema, inflammatory papules and pustules, phymatous change, or ocular ailments.3 rosacea erythema and flushing are frequently observed in erythematotelangiectatic or papulopustular subtypes. anecdotal reports have linked rosacea facial erythema to diminished quality of life and self-confidence. to date, effective treatment modalities remain scarce with limited efficacy, particularly for patients with telangiectasias or flushing. while the pathogenesis of facial erythema in rosacea and the role of btx-a remains unclear, neurogenic and immunologic etiologies have been thought to play a role. btx-a has been shown to diminish neurogenic inflammation by way of inhibiting vasodilating neuropeptides (acetylcholine and vasoactive intestinal peptide) and neurotransmitters (substance p and calcitonin gene-related peptide) which may play a role in rosacea’s complex mechanism.3 additionally, btx-a has been shown to significantly reduce mast cell counts and their subsequent proinflammatory and vasoactive secretions, which are regularly elevated in rosacea erythema.4 studies also suggest that upregulation of matrix metalloproteinases (mmps) may play a potential role in telangiectasia formation by influencing collagen formation.5 in one study by oh et al., btx-a has been reported to enhance type i collagen formation while also diminishing the influence of mmps on human dermal fibroblasts.6 significant clinical improvement and patient satisfaction were achieved with no major adverse effects. although the patient was concomitantly treated with both btx-a and isotretinoin, we attribute the reduction in erythema and flushing to her microdroplet btx-a treatments since her most significant improvement was observed in the injected areas. this study is limited by the potential confounder of isotretinoin treatment, lack of control group, and no scoring or grading system used to assess outcomes. btx-a administered as intradermal microdroplet injections can be a safe and efficacious option in the treatment of refractory rosacea, especially when lasers, topical, and systemic therapies have failed. conflict of interest disclosures: none funding: none corresponding author: natasha atanaskova mesinkovska, md, phd university of california, irvine department of dermatology 843 health sciences road, hewitt hall, room 1001 irvine, ca 92697 phone: (949) 824-7103 email: nmesinko@hs.uci.edu references: 1. hanna e, xing l, taylor jh, bertucci v. role of botulinum toxin a in improving facial erythema and skin quality. archives of dermatological research. published online 2021. doi:10.1007/s00403-021-02277-0 2. zhu j, ji x, xu y, et al. the efficacy of intradermal injection of type a botulinum toxin for facial rejuvenation. dermatologic therapy. 2017;30(1). doi:10.1111/dth.12433 3. kim mj, kim jh, cheon hi, et al. assessment of skin physiology change and safety after intradermal injections with botulinum toxin: a randomized, double-blind, placebocontrolled, splitface pilot study in rosacea patients with facial erythema. dermatologic surgery. 2019;45(9). doi:10.1097/dss.0000000000001819 4. dayan sh, pritzker rn, arkins jp. a new treatment regimen for rosacea: onabotulinumtoxina. journal of drugs in dermatology. 2012;11(12). skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 440 5. helfrich yr, maier le, cui y, et al. clinical, histologic, and molecular analysis of differences between erythematotelangiectatic rosacea and telangiectatic photoaging. jama dermatology. 2015;151(8). doi:10.1001/jamadermatol.2014.4728 6. oh sh, lee y, seo yj, et al. the potential effect of botulinum toxin type a on human dermal fibroblasts: an in vitro study. dermatologic surgery. 2012;38(10). doi:10.1111/j.1524-4725.2012.02504.x summaryobjective to evaluate the clinical efficacy of bimekizumab, using the mean percent change from baseline psoriasis area and severity index (pasi) through 16 weeks of treatment across four trials. introduction • bimekizumab is a monoclonal igg1 antibody that selectively inhibits both interleukin (il)-17a and il-17f.1,2 • individual phase 3/3b clinical trials have demonstrated the clinical efficacy of bimekizumab, including fast onset of response durable over two years as measured by pasi cutoff thresholds, for the treatment of patients with moderate to severe plaque psoriasis.3–6 • mean percent change from baseline pasi can be used by clinicians to characterize expected improvements in skin symptoms over time in patients initiating treatment with bimekizumab. methods • data from the bimekizumab treatment arms of four phase 3/3b trials, be ready (nct03410992)3, be vivid (nct03370133)4, be sure (nct03412747)5, and be radiant (nct03536884)6, were pooled. • included patients received bimekizumab 320 mg every four weeks (q4w) through week 16 (figure 1). • mean percent improvements from baseline pasi through week 16 are reported for the pooled cohort. pooled results from week 2 do not include be sure data, as pasi was not assessed at this timepoint. • missing data were imputed as last observation carried forward (locf). results • patient demographics and baseline characteristics for the pooled cohort are reported in table 1. • a total of 1,362 bimekizumab-treated patients were pooled. among these patients, mean percent improvements from baseline pasi at weeks 1, 2, 4, and 16 were 42.2%, 64.6%, 82.1%, and 95.9%, respectively (figure 2). • across all trials, the percentage of bimekizumab-treated patients who completed treatment through week 16 ranged from 95.3–97.4%. conclusions marked mean percent pasi improvements were observed as early as week 1 and continued to increase to week 16, showing that high levels of skin clearance were rapidly achieved in patients receiving bimekizumab. by showing average patient responses to bimekizumab, these data inform clinicians regarding expectations for bimekizumab treatment, allowing clinicians to clearly communicate the expectations of response to patients receiving bimekizumab. mean percent pasi improvement with bimekizumab in patients with moderate to severe plaque psoriasis: pooled results from four phase 3/3b trials abbreviations: bsa: body surface area; dlqi: dermatology life quality index; iga: investigator’s global assessment; il: interleukin; locf: last observation carried forward; pasi: psoriasis area and severity index; q4w: every 4 weeks; sd: standard deviation. institutions: 1oregon medical research center, portland, oregon, usa; 2icahn school of medicine at mount sinai, new york, new york, usa; 3department of dermatology university of texas health science center, houston, texas, usa; 4southern california dermatology; santa ana, california, usa; 5ucb pharma, smyrna, georgia, usa; 6ucb pharma, raleigh, north carolina, usa; 7ucb pharma, brussels, belgium references: 1glatt s et al. br j clin pharmacol 2017;83:991–1001; 2papp ka et al. j am acad dermatol 2018;79:277–286.e10; 3gordon kb et al. lancet 2021;397:475–86; 4reich k et al. lancet 2021;397:487–498; 5warren r et al. n engl j med 2021;385(2):130–141; 6reich k et al. n eng j med 2021; doi: 10.1056/nejmoa2102383. author contributions: substantial contributions to study conception/design, or acquisition/analysis/interpretation of data: ab, gh, skt, js, to, ld, vv, ml; drafting of the publication, or revising it critically for important intellectual content: ab, gh, skt, js, to, ld, vv, ml; final approval of the publication: ab, gh, skt, js, to, ld, vv, ml. author disclosures: ab: scientific adviser and/or clinical study investigator for abbvie, abcentra, aligos, almirall, amgen, arcutis, arena, athenex, boehringer ingelheim, bristol myers squibb, dermavant, eli lilly, evommune, forte, galderma, incyte, janssen, landos, leo pharma, novartis, pfizer, rapt, regeneron, sanofi genzyme, sun pharma, and ucb pharma; gh: consultant, speaker, or research support for abbvie, amgen, athenex, boehringer ingelheim, bond avillion, bristol myers squibb, castle biosciences, celgene, dermavant, dermtech, eli lilly, janssen, leo pharma, medx, mc2, novartis, ortho dermatologics, pfizer, regeneron, sanofi genzyme, sun pharma, and ucb pharma; skt: clinical study investigator for ucb pharma; js: honoraria and/or consulting fees from amgen, celgene, dermavant, national psoriasis foundation, ortho dermatologics and regeneron; grants and consulting fees from abbvie, actelion, boeringher ingelheim, dermira, eli lilly, janssen, leo pharma, novartis pharma and ucb; research grants from cassiopeia, galderma, and pfizer; to, ld: employees of ucb pharma; vv: employee and shareholder of ucb pharma; ml: employee of mount sinai and receives research funds from abbvie, amgen, arcutis, avotres, boehringer ingelheim, dermavant, eli lilly, incyte, janssen research & development, llc, ortho dermatologics, regeneron, and ucb pharma; consultant for aditum bio, anaptysbio, almirall, arcutis, aristea, arrive technology, avotres therapeutics, biomx, boehringer ingelheim, bristol myers squibb, cara therapeutics, castle biosciences, corrona, dermavant sciences, dr.reddy, evelo, evommune, facilitate international dermatologic education, forte, foundation for research and education in dermatology, helsinn, leo pharma, meiji, mindera, pfizer, seanergy, and verrica. acknowledgments: this study was funded by ucb pharma. we would like to thank the patients and their caregivers in addition to all of the investigators and their teams who contributed to this study. the authors acknowledge mylene serna, pharmd, ucb pharma, smyrna, ga, usa for publication coordination, and emily kaiser, bs, costello medical, boston, ma, usa for medical writing and editorial assistance. all costs associated with development of this presentation were funded by ucb pharma. pooled bimekizumab 320 mg q4w (n=1,362) age (years), mean ± sd 45.1 ± 13.6 male, n (%) 949 (69.7) caucasian, n (%) 1,188 (87.2) weight (kg), mean ± sd 89.7 ± 21.9 duration of psoriasis (years), mean ± sd 18.2 ± 12.6 pasi, mean ± sd 20.7 ± 7.6 bsa (%), mean ± sd 26.0 ± 15.6 iga, n (%) 3: moderate 896 (65.8) 4: severe 463 (34.0) dlqi, mean ± sd 10.5 ± 6.4 prior biologic therapy, n (%) 505 (37.1) table 1 baseline demographics and disease characteristics figure 2 pooled mean percent improvements from baseline pasi (locf) apooled results from week 2 do not include be sure data, as pasi was not assessed at this timepoint; bacross all trials, bimekizumab was dosed at baseline, and weeks 4, 8, 12, and 16. 0 10 20 30 40 50 60 70 80 90 0 4 8 12 16 m e a n im p ro v e m e n t in p a s i (% ) weeksb 1 2 100 bimekizumab 320 mg q4w (n=1,362)42.2 64.6a 82.1 95.9 presented at the fall clinical dermatology conference 2021 | october 21–24 | las vegas, nv # andrew blauvelt,1 george han,2 stephen k. tyring,3 jennifer soung,4 tae oh,5 leah davis,6 veerle vanvoorden,7 mark lebwohl2 week 16week 0 screening initial treatment period bimekizumab 320 mg q4w (n=1,362) be ready3 be vivid4 be sure5 be radiant6 be ready (nct03410992) mean percent pasi improvement with bimekizumab 320 mg q4w (n=1,362) be vivid (nct03370133) be sure (nct03412747) be radiant (nct03536884) data were pooled from the bimekizumab treatment arms of four phase 3/3b trials 42.2% week 1 week 2 64.6% week 4 82.1% week 16 95.9% figure 1 study design skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 435 brief articles black dot tinea capitis: magnified sonali nanda, ms1, valeria de bedout, md1, mariya miteva, md1, anna nichols, md, phd1,2 1department of dermatology and cutaneous surgery, university of miami miller school of medicine, miami, fl 2department of dermatology and cutaneous surgery, sylvester comprehensive cancer center, miami, fl a 2-year-old african american girl with no past medical history presented to dermatology with a one-month history of hair loss on the vertex of her scalp and associated mild itch. physical exam was significant for a well-demarcated patch of alopecia associated with black dots (figure 1). under trichoscopy, a prominent presentation of broken hairs was found, including a comma-shaped hair (blue arrow), a broken hair (green arrow) and a corkscrew hair (red arrow) (figure 2). woods lamp examination showed no fluorescence and lymph nodes were not palpable. fungal culture of the affected scalp returned positive for trichophyton species and a diagnosis of noninflammatory black dot tinea capitis was established. figure 1. a well-demarcated patch of hair loss on the vertex of the patient’s scalp case report skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 436 figure 2. trichoscopic image showing a corkscrew hair (red arrow), a comma hair (blue arrow), and a broken hair (green arrow) trichophyton species are responsible for greater than 90% of tinea capitis cases in north america.1 however, noninflammatory tinea capitis may be difficult to distinguish from other hair disorders in children such as seborrheic dermatitis, alopecia areata, trichotillomania, or langerhan histiocytosis as they can present with scaling, inflammatory papules, hair loss, or pruritis.1 in children with skin of color, erythema may be hard to appreciate, making it even harder to diagnose. trichoscopy is a fast, non-invasive and useful tool for the diagnosis in such cases. alopecia areata presents with black dots, dystrophic hairs, exclamation mark hairs, and circle hairs. circle hairs are thin, long, regularly twisted hairs with tapered ends compared to comma hairs which are dark, short hairs of uniform color, thickness, and sharp diagonal ends.2 trichotillomania displays black dots, broken hairs of variable lengths, coiled hairs, flame hairs, v-sign, and tulip hairs with surrounding normal hair. if trichoscopy is inconclusive, koh test, fungal culture, or biopsy can be helpful. in this case, clinical and trichoscopic exams were consistent with non-inflammatory “black dot” tinea capitis characterized by well-demarcated patches with black dots visualized on trichoscopy that represent broken hairs at or just below the scalp surface. the trichophyton species most commonly infect hairs in an ectothrix pattern where arthroconidia attach themselves around the hair shaft. these hairs become brittle and break at the level of the scalp, leaving microscopic ‘dots’ that represent the remaining hair in the follicle.1 under magnification, tinea capitis can present with many microscopic findings including broken hairs, corkscrew hairs, comma hairs, barcode hairs, zigzag hairs, and black dots.3 comma hairs, seen on the scalps of all skin types, are specific for tinea capitis, whereas corkscrew hairs have been described only in african-american children.2 identifying comma hairs spares the need for biopsy in children by excluding the most common differential diagnoses of patchy alopecia in this age. treatment involves systemic antifungal therapy with griseofulvin or terbinafine, as they have the highest clinical and mycologic cure rates.4 the duration is 4-6 weeks with terbinafine or 6-12 weeks with griseofulvin. terbinafine is the treatment of choice for tinea capitis caused by trichophyton spp. whereas griseofulvin remains first choice for tinea capitis caused by microsporum canis.4 all close-contacts should be examined and started on antifungal shampoo long-term.1 the patient was prescribed griseofulvin 25 discussion skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 437 mg/kg/day twice daily for 6 weeks, which resulted in complete resolution. conflict of interest disclosures: none funding: none corresponding author: sonali nanda, ms university of virginia school of medicine department of dermatology 1215 lee street charlottesville va, 22908 email: sn4z@virginia.edu references: 1. gupta, a. k. & summerbell, r. c. tinea capitis. med mycol 38, 255-287 (2000). 2. slowinska, m. et al. comma hairs: a dermatoscopic marker for tinea capitis: a rapid diagnostic method. j am acad dermatol 59, s77-79, doi:10.1016/j.jaad.2008.07.009 (2008). 3. bourezane, y. & bourezane, y. analysis of trichoscopic signs observed in 24 patients presenting tinea capitis: hypotheses based on physiopathology and proposed new classification. ann dermatol venereol 144, 490496, doi:10.1016/j.annder.2016.12.012 (2017). 4. gupta, a. k. et al. tinea capitis in children: a systematic review of management. j eur acad dermatol venereol, doi:10.1111/jdv.15088 (2018). mailto:sn4z@virginia.edu skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 459 short communications schwannoma of the scalp mimicking a pilar cyst peter w. hashim, md, mhs1, stephanie liu, do, mba1, garrett t. desman, md1, cerrene n. giordano, md1 1department of dermatology, icahn school of medicine at mount sinai, new york, ny schwannomas are benign nerve sheath tumors comprised of myelin-producing schwann cells. head and neck schwannomas constitute roughly 25% of cases, but lesions of the scalp are uncommon. (1-3) here, we describe a schwannoma of the scalp that clinically presented as a pilar cyst. a 17-year-old male presented with a fiveyear history of a subcutaneous nodule located on his occipital scalp. the patient noted slight growth of the lesion over the past six months and complained of intermittent tenderness. he denied any discharge from the area. he was interested in surgical removal due to the clinical symptoms. his medical history included nodulocystic acne. physical examination revealed a 2.3 cm x 2.3 cm firm, mobile, subcutaneous nodule of the midline occipital scalp (figure 1). no central punctum was noted. a pilar cyst was suspected. the lesion was excised under local anesthesia and was removed, without difficulty, as a solitary, encapsulated mass. histologic examination revealed a circumscribed dermal proliferation of spindle cells with nuclei arranged in parallel rows and separated by an eosinophilic fibrillar material (figure 2). the neoplasm was surrounded by a well-defined capsule partially composed of a compressed peripheral nerve. figure 1. midline occipital scalp with the outlined border of the schwannoma. introduction case report skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 460 figure 2. histological section (h&e, 20x) showing a dermal spindle cell proliferation. schwannomas most often appear between the 3rd and 5th decade and show equal prevalence between males and females. (2) over 90% arise sporadically as solitary lesions, with a natural history of slow growth and an absence of symptoms. (4). schwannomas of the head and neck region most often occur intracranially, including the bilateral “acoustic neuromas” diagnostic of type 2 neurofibromatosis. schwannomas are generally considered benign neoplasms, although malignant lesions have been reported, including on the scalp. (5) in our case, the patient’s lesion was largely asymptomatic, only becoming tender after several years of slow growth. excision was straightforward given the well-encapsulated nature of the tumor. this case adds to the small number of reported schwannomas occurring in the superficial tissues of the scalp, an uncommon location even amongst head and neck schwannomas. (6) the differential diagnosis of a firm, mobile, subcutaneous nodule of the scalp typically includes pilar cyst as well as the less common dermoid cyst, pilomatricoma, and lipoma. schwannomas are not typically suspected, as lesions of the scalp are rarely reported. (1, 3) this report highlights that a solitary scalp schwannoma can be included as an unlikely possibility. surgery for more symptomatic lesions remains the treatment of choice. conflict of interest disclosures: none funding: none corresponding author: cerrene n. giordano, md department of dermatology, icahn school of medicine at mount sinai 325 west 15th street new york, ny 10011 tel: (212) 367-0145 email: cerrene.giordano@gmail.com references: 1. asuquo me, nwagbara vi, akpan so, otobo fo, umeh j, ebughe g, et al. recurrent benign schwannoma of the scalp: case report. int j surg case rep. 2013;4(1):65-7. 2. langner e, del negro a, akashi hk, araujo pp, tincani aj, martins as. schwannomas in the head and neck: retrospective analysis of 21 patients and review of the literature. sao paulo med j. 2007;125(4):220-2. 3. mohan k, manjunath h. cutaneous schwannoma masquerading as trichilemmal cyst over scalp in a young male. indian j dermatol. 2013;58(5):407. 4. beaman fd, kransdorf mj, menke dm. schwannoma: radiologic-pathologic correlation. radiographics. 2004;24(5):1477-81. 5. demir y, tokyol c. superficial malignant schwannoma of the scalp. dermatol surg. 2003;29(8):879-81. 6. leu ys, chang kc. extracranial head and neck schwannomas: a review of 8 years experience. acta otolaryngol. 2002;122(4):435-7. discussion mailto:cerrene.giordano@gmail.com skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 451 skimages erythrasma under wood’s lamp and the “coral-red” glow danny zakria, md, mba1, nicholas d. brownstone, md2, mckenzie a. dirr, ba, bs3, darrell rigel, md, ms4 1 national society for cutaneous medicine, new york, ny 2 department of dermatology, temple health, philadelphia, pa 3 medical university of south carolina, charleston, sc 4 department of dermatology, mount sinai icahn school of medicine, new york, ny we present a case in which a 54-year-old male with fitzpatrick skin type ii presented to clinic with well-circumscribed dark brown patches with surrounding scale in his bilateral inguinal folds. he reported that he first noticed the rash about two weeks prior to presentation and applied otc anti-fungal creams with no improvement. he stated that he has never had a similar rash before, and he noted that the only associated symptom was occasional pruritus. examination with wood’s lamp revealed a bright “coral-red” fluorescence (figure 1) and helped confirm the diagnosis of erythrasma. erythrasma is a cutaneous bacterial infection most commonly caused by corynebacterium minutissimum.1 corynebacterium minutissimum is a grampositive bacillus that constitutes the normal figure 1. coral red fluorescence characteristic of erythrasma skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 452 microflora of the skin.2 it has a predilection for moist areas of the body such as the axillae, inframammary folds, interdigit spaces, and the intergluteal cleft.1 c. minutissimum produces a chemical called coproporphyrin type iii, which leads to the characteristic “coral-red” glow when examined under wood’s lamp.2 importantly, bathing can remove the porphyrin and lead to a false-negative result.2 erythrasma classically presents as well-demarcated dark-brown macules and later coalesces into larger patches in intertriginous skin.3 the rash can be confused with other common pathology including candidiasis, dermatophytosis, pityriasis versicolor, and inverse psoriasis. candidiasis is a fungal infection most commonly caused by candida albicans.1 the rash is typically erythematous and scaly with evidence of satellite lesions. dermatophyte infections can also present as erythematous and scaly plaques. both candidiasis and dermatophyte infections can be identified using potassium hydroxide preparation.1 of note, approximately 30% of patients with interdigital erythrasma may have a coexisting dermatophyte or candida infection. pityriasis versicolor lesions can be hyperpigmented or hypopigmented but usually do not feature scale or welldemarcated borders as seen in erythrasma. inverse psoriasis presents as an erythematous, non-scaly plaque in intertriginous lesions. wood’s lamp offers a quick and non-invasive method of diagnosing erythrasma and distinguishing it from these other similar conditions. there are several treatment options for erythrasma including both topical and systemic therapy. topical therapy consists of clindamycin, fusidic acid, mupirocin, and whitfield’s ointment while systemic therapy includes oral clarithromycin, erythromycin, and tetracycline.4 there is no consensus on optimal first-line agent, but topical therapy is generally preferred to limit adverse effects.1 for intertriginous disease, it is important to add a topical agent, often in conjunction with systemic therapy, in order to obtain clearance.4 while there is limited data on duration of treatment, most studies suggest a 2-week course. a thorough hpi, high index of suspicion and appropriate use/interpretation of the wood’s lamp exam can allow for quicker diagnosis and effective therapy. conflict of interest disclosures: none funding: none corresponding author: danny zakria, md, mba national society for cutaneous medicine one harbor square suite 325 ossining, ny 10562 email: dzakria13@gmail.com references: 1. forouzan p, cohen pr. erythrasma revisited: diagnosis, differential diagnoses, and comprehensive review of treatment. cureus. 2020;12(9):e10733. published 2020 sep 30. doi:10.7759/cureus.10733 2. chen d, ferringer tc. red-brown patches in the groin. cutis. 2018;101(6):416-420. 3. riquelme il, moyano eg. axillary and inguinal erythrasma. cmaj. 2021;193(39):e1535. doi:10.1503/cmaj.210310 4. holdiness mr. management of cutaneous erythrasma. drugs. 2002;62(8):1131-1141. doi:10.2165/00003495-200262080-00002 acknowledgements study funded and editorial/poster support provided galderma laboratories, l.p. two on-label injection volumes of abobotulinumtoxina (abo) produce similar safety and efficacy results when used to treat moderate to severe glabellar lines joely kaufman, md1; joel cohen, md2; marina peredo, md3; brandie jonas, ms4; alessandra nogueira, md4; jay h. mashburn, phd4 1skin associates of south florida, skin research institute, coral gables, fl; 2director of aboutskin dermatology and dermsurgery, greenwood village and lone tree, co, associate clinical professor, department of dermatology, university of colorado; assistant clinical professor, department of dermatology, university of california irvine; 3marina i. peredo, md, smithtown, ny; 4galderma laboratories, l.p., fort worth, tx dys.p-ma10348-06 introduction • two injection volumes (0.05 ml and 0.08 ml) of dysport® (abobotulinumtoxina [abo]; manufactured by ipsen biopharm ltd, wrexham, uk), reconstituted in either 1.5 ml or 2.5 ml of sterile preservative-free 0.9% sodium chloride for injection usp, respectively, are approved for the treatment of glabellar lines (gls)1 • even though both injection volumes are approved for reconstitution in the us label, many injectors tend to believe that with the higher dilution volumes of neurotoxins, the greater risk of toxin spread or other unwanted safety issues2 • this study aimed to show both injection volumes result in similar efficacy and safety profiles references 1. dysport®. prescribing information. fort worth, tx: galderma laboratories, l.p., 2016. 2. trindade de almeida ar, secco lc, carruthers a. handling botulinum toxins: an updated literature review. dermatol surg. 2011 nov;37(11):1553-1565. 3. honeck p, weiss c, sterry s, gladys study group, et al. reproducibility of a four-point clinical severity score for glabellar frown lines. br j dermatol. 2003;149:306-310. summary ■ the study results demonstrated that treatment of moderate-to-severe gls with either on-label injection volume resulted in almost identical efficacy and safety profiles, rapid onset of effect, and provided a high degree of clinician and subject satisfaction. ■ responder rates for each treatment group were generally similar among all evaluations with the exception of ≥ 1-point composite responders at maximum frown at day 2 (~ 24 hours post-treatment) where abo 2.5 ml treatment group (group b) had a statistically significant larger number of responders compared to abo 1.5 ml treatment group (group a; p = .0377). ■ high levels of subject satisfaction with appearance and natural looking outcome were maintained through day 120. ■ both treatments provided a natural looking aesthetic outcome and were found to be safe and well tolerated. the results of this study demonstrated that the higher injection volume produced similar effects for improvement of gl severity and did not result in increased safety concerns compared to the lower volume. subjects and methods subject selection and methods • this 120 day, multi-center, randomized, subjectand evaluator-blinded study enrolled subjects with moderate glabellar line severity scores (glss=2) to severe (glss=3) who were naïve to botulinum toxin treatment in the facial area • subjects were randomized (by age, gender, blinded evaluator glss) to receive either 0.05 ml/ injection (group a) or 0.08 ml/injection (group b). subjects received 1 treatment which consisted of 5 injections in the glabellar area. each subject received a total of 50 u (10 u/injection site) of abo. primary efficacy endpoint • the proportion of composite responders (defined as subjects who achieved at least a 1-point reduction from baseline in the glss at maximum frown, based on the combined blinded evaluator and subject assessments), at 30 days post-treatment using a validated 4-point photographic scale3 for evaluators and a static 4-point categorical scale for subjects secondary endpoints • subject and blinded evaluator assessment for onset of effect (ooe) at all time points • the proportion of ≥1-point and ≥ 2-point composite responders at each study visit, by evaluating the glss change from baseline (subject, blinded evaluator, and treating investigator assessments) • treating investigator satisfaction at day 30 using 5-point likert scale • subject satisfaction with appearance and naturalness of results using a subject questionnaire and 5-point likert scale (1=strongly disagree; 5=strongly agree) at 30 and 120 days posttreatment • evaluation of treatment emergent adverse events (teaes) reported during the study results demographics • sixty subjects (24-64 years old; mean age of 45.8 years) were enrolled. subjects were primarily female (86.7%) and caucasian (96.7%) with moderate (25%) and severe (75%) glls scores at maximum frown (baseline). glabellar line severity scores • 46.7% of subjects achieved at least a 1-point reduction in glss (based on combined subject and blinded evaluator assessments) within 48 hours using either injection volume, this increased to 88.3% overall by 30 days post-treatment (figure 1, representative photographs) • at 48 hours post-treatment, 46.7% of subjects in both treatment groups were composite responders with an increase to 70.0% (group a) and 76.7% (group b) by 72 hours post-treatment (figure 2a). the only statistically significant difference between treatments was noted at 24 hours post-treatment, where 26.7% of subjects in group b were considered composite responders compared to only 6.7% in group a (p=.0377; figure 2a) • at 30 day post-treatment, 90.0% of subjects in group a and 86.7% of subjects in group b were considered composite responders (figure 2a) • for group a composite responders at day 30, 70.0% achieved at least a 2-point reduction from baseline in glss. for group b composite responders at day 30, 63.3% achieved at least a 2-point reduction from baseline in glss (figure 2b). onset of effect • as early as 24 hours post-treatment, ooe was reported for 30.0% of subjects (based on combined subject and blinded evaluator assessments) with no significant difference between treatment groups. within 48 hours, 73.3% of subjects had reported ooe. • within 24 hours post-treatment, 26.7% of subjects in group a and 33.3% of subjects in group b experienced ooe (based on subject and blinded evaluator assessments); this increased to 76.7% and 70.0% within 48 hours post-treatment, respectively (figure 3). treating investigator satisfaction • investigators reported high satisfaction for both treatments subject satisfaction • at 30 days post-treatment, the majority of subjects (80.0% group a, 83.3% group b) agreed or strongly agreed they were satisfied with how they looked compared to baseline (16.7% group a, 16.7% group b) and most subjects remained in agreement at day 120 (63.3% group a, 66.7% group b; figure 4a) • at 30 days post-treatment, the majority of subjects (90.0% group a, 93.3% group b) agreed or strongly agreed that treatment provided a natural looking appearance compared to baseline (40.0% group a, 36.7% group b) and most subjects remained in agreement at day 120 (80.0% group a, 80.0% group b; figure 4b) safety • a total of 13 treatment emergent adverse events (teaes) were reported in 6 subjects (3 subjects from each treatment group); 9 teaes reported in 3 subjects were assessed as related to treatment (2 subjects in group a, 1 subject in group b; table 1) • no saes were reported and both treatments were well-tolerated 26.7 33.3 76.7 70.0 90.0 83.3 93.3 96.7 0 20 40 60 80 100 24 hrs 48 hrs 72 hrs 7 days 9 days time, post-treatment pe rce nt o f s ub je cts group a (n=30) group b (n=30) 96.793.3 figure 3. proportion of subjects who achieved onset of effect (ooe), based on combined subject and blinded evaluator assessments (n = 60) – mitt population 1.5 ml = 0.05 ml/injection, n=30; 2.5 ml = 0.08 ml/injection, n=30; mitt = modified intent to treat 6.7 46.7 70.0 86.7 93.3 90.0 56.7 43.326.7 46.7 76.7 83.3 90.0 86.7 66.7 46.7 0 20 40 60 80 100 24 hrs 48 hrs * 72 hrs 6 days 2 weeks 4 weeks 3 months 4 months group a (n = 30) group b (n = 30) time, post-treatment % o f s ub je cts 10 30 40 60 0 20 50 70 80 90 100 i am satisfied with how i look pe rce nt o f s ub je cts , a gr ee /s tro ng ly ag re e baseline day 30 day 120 66.7 63.3 83.3 80.0 16.7 16.7 group a (n=30) group b (n=30) 10.0 3.3 46.7 46.7 63.3 63.3 3.3 16.7 0.0 16.7 6.7 63.3 70.0 13.3 26.7 0 20 40 60 80 100 24 hrs 48 hrs 72 hrs 6 days 2 weeks 4 weeks 3 months 4 months group a (n = 30) group b (n = 30) time, post-treatment 10 30 40 60 0 20 50 70 80 90 100 my face looks natural pe rce nt o f s ub je cts , a gr ee /s tro ng ly ag re e baseline day 30 day 120 80.080.0 93.3 90.0 40.0 36.7 group a (n=30) group b (n=30) figure 4. subject satisfaction at days 30 and 120, relative to baseline (n=60) – mitt population 2a) proportion of composite responders with at least a 1-point reduction from baseline in glss, maximum frown (n = 60); mitt population 4a) subject satisfaction, satisfaction with overall look 2b) proportion of composite responders with at least a 2-point reduction from baseline in glss, maximum frown (n = 60); mitt population group a (1.5 ml) – 0.05 ml/injection; group b (2.5 ml) – 0.08 ml/injection; *p=.0377, group a compared to group b; composite responders = based on combined subject and blinded evaluator assessments; mitt = modified intent to treat group a (1.5 ml) – 0.05 ml/injection; group b (2.5 ml) – 0.08 ml/injection; composite responders = based on combined subject and blinded evaluator assessments; mitt = modified intent to treat group a (1.5 ml) – 0.05 ml/injection; group b (2.5 ml) – 0.08 ml/injection; mitt = modified intent to treat group a (1.5 ml) – 0.05 ml/injection; group b (2.5 ml) – 0.08 ml/injection; mitt = modified intent to treat table 1. summary of treatment-emergent adverse events (teaes) group a (n=30) group b (n=30) number of subjects with ≥ 1 teae, n (%) 3 (10) 3 (10) number of subjects with related teae, n (%)* 2 (6.7) 1 (3.3) vision blurred 1 (3.3) 0 (0) injection site pain 1 (3.3) 0 (0) injection site swelling 1 (3.3) 0 (0) headache 2 (6.7) 0 (0) migraine 1 (3.3) 0 (0) dry skin 1 (3.3) 0 (0) skin hyperpgimentation 0 (0) 1 (3.3) number of subjects with not related teae, n (%) 1 (3.3) 2 (6.7) seasonal allergies 1 (3.3) 0 (0) bronchitis 0 (0) 1 (3.3) nasopharyngitis 0 (0) 1 (3.3) dermatitis contact 1 (3.3) 0 (0) safety population = 60 subjects. group a (1.5 ml) – 0.05 ml/injection; group b (2.5 ml) – 0.08 ml/ injection. counts reflect the number of subjects experiencing teaes, not the number of teaes. *one subject had multiple events: headache, migraine, injection site pain, and injection site swelling 43b) subject satisfaction, natural looking appearance baseline max frown glss = 3 day 30 max frown glss = 0 figure 1. representative photographs subject 138-003 figure 2. proportion of composite responders treated with 1.5 ml reconstitution fc17postergaldermakaufmantwoonlabelvolumes.pdf skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 195 in-depth review hidradenitis suppurativa and down syndrome: systematic review and meta-analysis niyaz mostafa, md1,2, kevin phan, md1,2,3, tajrian amin, md1,saxon d. smith, mbchb, phd4 1 faculty of medicine, university of new south wales (unsw), sydney, australia 2 st. george dermatology and skin cancer centre, kogarah, australia 3 department of dermatology, liverpool hospital, sydney, australia 4 the dermatology and skin centre, gosford, australia hidradenitis suppurativa (hs) is a chronic, inflammatory skin disease that affects 1-4% of the population1–3. it is characterized by the presence of painful lesions and recurrent abscesses, and nodules affecting the skin. these lesions can later rupture to form sinus tracts and fistulas. hs is a progressive disease that is debilitating and can impact an individual across physical, social and emotional domains, which is worsened in the absence of adequate management. the exact etiology of hs is currently unknown, however a link between genetic, social and environmental factors has been postulated in recent studies1–3. down syndrome, also known as trisomy 21, is one of the most common chromosomal disorders affecting chromosome 21. it presents with a number of features in affected patients including, intellectual abstract introduction: hidradenitis suppurativa (hs) is a chronic, inflammatory skin disease, characterized by the presence of painful lesions and recurrent abscesses, and nodules. these lesions can later rupture to form sinus tracts and fistulas. the exact etiology of hs is currently unknown, however a link between genetic, social and environmental factors has been postulated in recent studies. a number of studies have shown a significant association between hs and down syndrome (ds), however the relationship between hs and ds is unclear. we conducted a systematic review and meta-analysis to test for any association between hs and down syndrome. methods: a systematic review of existing studies was performed and data was pooled for metaanalysis. reviews, abstracts and case reports were excluded. eligible studies were those which investigated hs in cases of down syndrome. studies that reported ds cases amongst hs patients were not included in the present study. results: a total of 6 studies were identified from systematic database searches after applying inclusion and exclusion criteria. pooled meta-analysis demonstrated a significant association between hs and down syndrome. the pooled proportion of hs cases in the ds group was 10.9% (95% ci, 3.8%-27.6%). the pooled proportion of hs cases in the control group was 0.4% (95% ci, 0.2%-0.8%). this difference was significantly different (p<0.001). the odds ratio is 12.02(95% ci 10.91-13.23). conclusion: the evidence for hidradenitis suppurativa being associated with down syndrome is very limited. the data is promising however, and further prospective studies with larger cohorts are required to reaffirm the findings in the present review. introduction skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 196 disability, congenital heart disease as well as other diseases involving different systems of the body4. ds affects between 1 in 400-1500 babies born across different populations, which varies according to maternal age and screening schedules in the prenatal period5. there is an increased prevalence of mucocutaneous disorders amongst ds patients in comparison to the general population source 6. a number of studies have shown a significant association between hs and down syndrome (ds)7–12, however the relationship between hs and ds is unclear. we conducted a systematic review and meta-analysis to test for any association between hs and down syndrome. search strategy we performed a systematic review and meta-analysis in accordance to the recommended preferred reporting items for systematic reviews and meta-analyses (prisma) guidelines. the search was performed in 2021 and electronic searches were performed using ovid medline, pubmed, cochrane central register of controlled trials (cctr), cochrane database of systematic reviews (cdsr), acp journal club, and database of abstracts of review of effectiveness (dare) from their dates of inception to august 2021. search terms included: “hidradenitis suppurativa”, “hidradenitis suppurative”, “acne inversa”, “velpeau”, “verneuil” combined with “down syndrome” or “trisomy 21”. the resulting articles were assessed systematically by two independent reviewers using the inclusion and exclusion criteria. selection criteria all eligible studies included those investigating the presence of hs in a population of down syndrome patients. studies that reported ds cases amongst hs patients were not included in the present study. all studies must have included either the proportion of patients with hs in each group or the summary effect size for association between hs and ds. data extraction and quality assessment the data was extracted by two independent reviewers from articles text, tables and figures. the data of interest included study type, location, demographic data and information related to the proportion of patients with hs in a ds patient population. the quality of the studies was assessed using the newcastle-ottawa scale. statistical analysis firstly, to establish variance of raw proportions, a logit proportion transformation was applied. to incorporate heterogeneity (anticipated among the included studies), transformed proportions were combined using dersimonian-laird random effects models. finally the pooled estimates were back-transformed. heterogeneity was evaluated using cochran q and i2 test. meta-regression based on subgroup (down syndrome versus controls) was performed. all analyses were performed using the metafor package for r version 3. p values <0.05 were considered statistically significant. a total of 30 studies were identified from the electronic database search. after applying inclusion and exclusion criteria, six studies were included for the present systematic review and meta-analysis (figure 1). methods results skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 197 study characteristics study characteristics and demographic data are summarized in table 1. four studies were retrospective and observational in nature7,9–11, whereas the other 2 included studies were case-control studies8,12. three studies reported age ranges8,10,11 and only garg et al.8 adjusted their statistical analysis for confounding factors. assessment of study bias the risk of bias in this study was evaluated using the newcastle ottawa scale for cohort and cross-sectional studies the results are summarized in table 1. a majority of studies scored 7 or higher, indicating a low level of bias amongst the studies. association between hs and ds pooled meta-analysis demonstrated a significant association between hs and down syndrome (figure 1) . the pooled proportion of hs cases in the ds group was 10.9% (95% ci, 3.8%-27.6%). the pooled proportion of hs cases in the control group was 0.4% (95% ci, 0.2%-0.8%). this difference was significantly different (p<0.001). the odds ratio is 12.02(95% ci 10.91-13.23). from the present meta-analysis and systematic review of observational and case-control studies, we demonstrated a significant association between hs and down syndrome. our findings add to the limited, but expanding body of literature that hs and other follicular disorders may be associated with ds. treating clinicians should be aware of the potential link between these 2 conditions in order to institute early intervention in future ds patients. the exact etiology of hs in ds remains unclear, however our findings suggests that there may be some form of genetic predisposition to hs in down syndrome patients as postulated in other studies13.the link between hs and ds may be related to the increased expression of amyloid precursor protein (app), normally encoded by a gene located on chromosome 2114. in ds patients, cleavage of app by gammasecretase leads to the formation of betaamyloid plaques. the presence of the plaques leads to patients developing alzheimer’s disease earlier in life compared to the general population. app also plays a role in the epidermis, particularly in stimulating the adhesion, migration and proliferation of keratinocytes15. increased app in ds patients may cause the hyperproliferation of keratinocytes and plugging of follicles, which is seen histopathologically as features in hs. gamma contributing to this theory, in familial hs, functional mutations of genes encoding the gamma-secretase protein complex have been observed16. mutations in gammasecretase and increased app in ds may also lead to a defective notch signalling pathway and altered pro-inflammatory effects down the line13,17. this includes inadequate suppression of the innate immune system, causing inflammation, a hallmark of hs, as well as the inhibition of natural killer cell activity. another potential link between hs and ds is the shared comorbidity of obesity. there are table 1. study characteristics discussion skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 198 na, not reported; nos, newcastle-ottawa scale for study quality; 1, age reported as means in different age groups; 2, age reported as median and range; 3, age reported as mean and standard deviation figure 1. prisma flowchart study location design cases/con trols females % (cases/ control) age in years( cases/control) adjustment nos firsowicz et al., pediatr dermatol, 2020 usa retrospective observational 243/0 na na na 7 garg et al., br j dermatol, 2018 usa case-control 11936/1681 3290 60/44 18-291 36/18 down syndrome, age, sex, race, obesity 7 30-39 23/16 ≥ 40 41/66 hamadah et al., pediatr dermatol, 2017 saudi arabia retrospective observational 29/0 na na na 7 poizeau et al., acta derm venerol, 2019 france retrospective observational 783/0 46/0 hs non-hs na 7 23 (1053)/02 31(9-67)/0 rork et al., pediatr dermatol, 2020 usa retrospective observational 101/0 39/0 19.7 (15.9)/03 na 8 sechi et al., dermatol pract concept, 2019 italy case-control 131/12351 42/38 na na 6 skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 199 figure 2. forest plot assessing the relationship between hidradenitis suppurativa and down syndrome compared to controls. increased frequencies of obesity in children with ds in comparison to healthy children18. this common comorbidity between both diseases may mean that obesity in patients with ds may predispose them to hs19,20 hs is also associated with several other comorbidities including smoking, dyslipidaemia, diabetes mellitus and metabolic syndrome3 as well as those associated with the integumentary system such as acne and pilonidal disease21. recent evidence based recommendations from the us and canadian hs foundations suggest regular screening for such comorbidities as well as screening ds patients for hs22. the decision to screen for certain diseases should vary based on patient risk factors. the present review has several limitations. the studies included were composed of both case-control and observational studies, which were mostly retrospective, making them susceptible to selection and assessment bias. confounder variables may have influenced the analysed effect sizes, which were unadjusted. data for a majority of studies was obtained from large databases which may have errors in coding disease parameters, and there is likely heterogeneity between the criteria used for hs and down syndrome diagnosis. prospective studies with larger cohorts are required to reaffirm the findings in the present review. pooled analysis of existing studies reveals that patients with ds are associated with an increased risk of hs in comparison to controls. dermatologists and other clinicians involved in the care of patients with ds should be aware of this association and implement early screening and intervention based on risk factors in this cohort. conflict of interest disclosures: none funding: none corresponding author: niyaz mostafa university of new south wales faculty of medicine sydney, australia, 2052 email: nmostafa.research@gmail.com references: 1. vekic da, frew j, cains gd. hidradenitis suppurativa, a review of pathogenesis, associations discussion skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 200 and management. part 1. australas j dermatol. 2018;59(4):267-277. doi:10.1111/ajd.12770 2. fimmel s, zouboulis cc. comorbidities of hidradenitis suppurativa (acne inversa). dermatoendocrinol. 2010;2(1):9-16. doi:10.4161/derm.2.1.12490 3. garg a, kirby js, lavian j, lin g, strunk a. sex and age-adjusted population analysis of prevalence estimates for hidradenitis suppurativa in the united states. jama dermatology. 2017;153(8):760-764. doi:10.1001/jamadermatol.2017.0201 4. roizen nj, patterson d. down’s syndrome. lancet. 2003;361(9365):1281-1289. doi:10.1016/s01406736(03)12987-x 5. kazemi m, salehi m, kheirollahi m. down syndrome: current status, challenges and future perspectives. int j mol cell med. 2016;5(3):125133. 6. daneshpazhooh m, nazemi tmj, bigdeloo l, yoosefi m. mucocutaneous findings in 100 children with down syndrome. pediatr dermatol. 2007;24(3):317-320. doi:10.1111/j.15251470.2007.00412.x 7. firsowicz m, boyd m, jacks sk. follicular occlusion disorders in down syndrome patients. pediatr dermatol. 2020;37(1):219-221. doi:10.1111/pde.14012 8. garg a, strunk a, midura m, papagermanos v, pomerantz h. prevalence of hidradenitis suppurativa among patients with down syndrome: a population-based cross-sectional analysis. br j dermatol. 2018;178(3):697-703. doi:10.1111/bjd.15770 9. hamadah i, haider m, chisti m, binamer y. hidradenitis suppurativa in down syndrome: a case series. pediatr dermatol. 2017;34(4):461464. doi:10.1111/pde.13188 10. poizeau f, sbidian e, mircher c, et al. prevalence and description of hidradenitis suppurativa in down syndrome: a cross-sectional study of 783 subjects. acta derm venereol. 2019;99(3):351352. doi:10.2340/00015555-3095 11. rork jf, mccormack l, lal k, wiss k, belazarian l. dermatologic conditions in down syndrome: a single-center retrospective chart review. pediatr dermatol. published online june 10, 2020. doi:10.1111/pde.14214 12. sechi a, guglielmo a, patrizi a, et al. disseminate recurrent folliculitis and hidradenitis suppurativa are associated conditions: results from a retrospective study of 131 patients with down syndrome and a cohort of 12,351 pediatric controls. dermatol pract concept. 2019;9(3):187194. doi:10.5826/dpc.0903a03 13. blok j, jonkman m, horváth b. the possible association of hidradenitis suppurativa and down syndrome: is increased amyloid precursor protein expression resulting in impaired notch signalling the missing link? br j dermatol. 2014;170(6):13751377. doi:10.1111/bjd.12887 14. jenkins ec, devine-gage ea, robakis nk, et al. fine mapping of an alzheimer disease-associated gene encoding beta-amyloid protein. biochem biophys res commun. 1988;151(1):1-8. doi:10.1016/0006-291x(88)90551-7 15. herzog v, kirfel g, siemes c, schmitz a. biological roles of app in the epidermis. eur j cell biol. 2004;83(11-12):613-624. doi:10.1078/0171-933500401 16. wang b, yang w, wen w, et al. gamma-secretase gene mutations in familial acne inversa. science. 2010;330(6007):1065. doi:10.1126/science.1196284 17. melnik bc, plewig g. impaired notch-mkp-1 signalling in hidradenitis suppurativa: an approach to pathogenesis by evidence from translational biology. exp dermatol. 2013;22(3):172-177. doi:10.1111/exd.12098 18. rubin ss, rimmer jh, chicoine b, braddock d, mcguire de. overweight prevalence in persons with down syndrome. ment retard. 1998;36(3):175-181. doi:10.1352/00476765(1998)036<0175:opipwd>2.0.co;2 19. gold da, reeder vj, mahan mg, hamzavi ih. the prevalence of metabolic syndrome in patients with hidradenitis suppurativa. j am acad dermatol. 2014;70(4):699-703. doi:10.1016/j.jaad.2013.11.014 20. miller im, ellervik c, vinding gr, et al. association of metabolic syndrome and hidradenitis suppurativa. jama dermatol. 2014;150(12):12731280. doi:10.1001/jamadermatol.2014.1165 21. reddy s, strunk a, garg a. comparative overall comorbidity burden among patients with hidradenitis suppurativa. jama dermatol. 2019;155(7):797-802. doi:10.1001/jamadermatol.2019.0164 22. garg a, malviya n, strunk a, et al. comorbidity screening in hidradenitis suppurativa: evidencebased recommendations from the us and canadian hidradenitis suppurativa foundations. j am acad dermatol. published online january 23, 2021:s0190-9622(21)00213-9. doi:10.1016/j.jaad.2021.01.059 skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 680 brief article a cross-sectional survey of students and instructors on virtual dermatology teaching in a competency-based format shara chopra bs, ba,1 ankita sinharoy, mbbs, mph,2 alexandra flamm, md2 1penn state college of medicine, hershey, pa 2department of dermatology, penn state milton s. hershey medical center, hershey, pa in a traditional in-person teaching format, student learning is assessed by whether it fulfills the acgme (accreditation council for graduate medical education) core competencies: patient care, medical knowledge, practice-based learning and improvement, interpersonal and communication skills, professionalism, and systems-based practice.1 during the covid-19 pandemic, the dermatology elective at the penn state college of medicine (pscom) was converted to a fourweek virtual format in lieu of a clinical rotation. given this switch to virtual teaching, we aimed to assess fulfillment of these competencies in this learning format, as well as instructor and student satisfaction in order to identify components of virtual education that may be beneficial beyond the covid-19 pandemic. we conducted a cross-sectional observational study to assess student and instructor satisfaction to the virtual abstract background: due to the covid-19 pandemic in the spring of 2020, the dermatology rotation at the penn state college of medicine (pscom) was converted into a 4-week virtual format. given these rapid changes, we aimed to assess student and instructor satisfaction to the virtual course and if the course fulfilled the six acgme core-competencies for medical student education required in a traditional teaching format. methods: we conducted a cross-sectional study to assess pscom student and instructor satisfaction to the elective. surveys specifically inquired about course learning objectives, interaction, and teaching in the virtual setting based on a 5-point likert scale and asked the participants to provide qualitative feedback. results: medical students (n=15, response rate=52%) were satisfied with learning objectives geared towards the acgme core competencies in five of the six competencies. instructors (n=7, response rate=58%) reported satisfaction with convenience, university support, and technical training, but less with student-to-student interaction, gauging comprehension, and fostering critical thinking. qualitative feedback reflected these results. conclusions: from our survey data, students and instructors were generally satisfied with the virtual rotation’s dermatology teaching during the uncertain times of the covid-19 pandemic and holds potential to expand dermatology education, with a future focus on improving student engagement in a virtual format. introduction methods skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 681 dermatology elective from april 2020 through june 2020. pscom medical students (ms) were surveyed, including six ms1 (first-year) accelerated and 23 ms4 (fourth-year). surveyed instructors were dermatology residents (postgraduate year), including four pgy2, four pgy3, and four pgy4. students asynchronously followed the american academy of dermatology’s (aad) basic dermatology curriculum (https://www.aad.org/member/education/resi dents/bdc), covering morphology and the diagnosis and treatment of common skin conditions with an additional nine hours/week of course instruction.2,3 students interacted with the pscom’s dermatology faculty (not surveyed) and residents in thrice-weekly virtual lectures and casebased learning, expanding on the aad’s course. additional topics were covered in daily resident didactics, a once-weekly journal club, and outside assignments – including considerations of ethical dilemmas in dermatology and expanding on a basic science topic. survey tools were modified versions of previously validated instruments where participants rated satisfaction on a 5point likert scale about course learning objectives, interaction, and virtual instruction.4,5,6 qualitative feedback was also obtained. study data were collected and managed using redcap (research electronic data capture) tools hosted at the penn state health milton s. hershey medical center and pscom.7 this study received institutional review board exemption. twenty-nine medical students were surveyed with 15 students responding completely, yielding a 52% response rate. responses of agree and strongly agree were combined to assess satisfaction and fulfillment of core competency categories. an additional student survey was partially completed and included only the core competency data. student responses for learning objectives pertaining to the acgme core competencies were averaged (n=16), showed that 93.75% of students agreed the course fulfilled the competency for medical knowledge, 87.40% for patient care, 81.25% for systems-based practices, 78.75% for interpersonal and communication skills, 68.75% for professionalism, and 50% for practice-based learning and improvement. when asked if the virtual setting hindered learning (n=15), 6.67% of students stated this was a concern for the category of medical knowledge, 20% for clinical understanding, 26.66% for communication, and 0% for professionalism. twelve instructors were surveyed with a 58% response rate. instructors were satisfied with aspects of the course such as convenience, university support, technical training (100%), and the opportunity to reach a diverse student population (85.71%). instructors were less satisfied with studentto-student interaction (14.29%), gauging comprehension (14.29%), and fostering critical thinking (28.57%) (table 1). qualitative feedback reflected objective data. both groups enjoyed the convenience and flexibility of the course. students and instructors reported difficulty engaging during the virtual sessions and suggested practice material, telemedicine, and reduced results https://www.aad.org/member/education/residents/bdc https://www.aad.org/member/education/residents/bdc skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 682 table 1 student and instructor satisfaction to course learning and the virtual setting. student satisfaction core competency student response (% agree; n=16) medical knowledge 93.75 patient care 87.40 systems-based practices 81.25 interpersonal and communication skills 78.75 professionalism 68.75 practice-based learning and improvement 50 hindrance due to the virtual setting student response (% agree; n=15) medical knowledge 6.67 clinical understanding 20 communication 26.66 professionalism 0 instructor satisfaction virtual teaching and efficacy instructor response (% agree; n=7) student’ appear to be an online community 14.29 gauging student comprehension 14.29 foster critical thinking 28.57 students are passive in interactions 85.71 could not get to know students 85.71 diverse student population 85.71 content quality 85.71 training needs were met 100 adequate tools and support 100 convenience 100 class sizes as possible ways to overcome these barriers (table 2). while medical students were able to return to the clinical setting by the fall of 2020, hybrid and virtual learning will likely continue to be an important component of dermatology education in the future. the data and opinions gleaned in this setting can be of use in improving virtual education offerings. the patient environment continues to be indispensable as repetitive exposure aids in achieving skills of describing morphology, learning the basic skin exam, and performing diagnostic and therapeutic procedures.8 although 93% of institutions offer a dermatology clerkship as a fourthyear elective, only on average 16.3 hours of total dermatology instruction are required in most medical curricula.9 a mixed curriculum of online didactics, self-directed learning, and in-person clinical immersion may allow for increasing the number of students exposed to dermatology clinically, especially those who may be traveling from a different campus or medical school. this represents an opportunity for reduced cost of travel and housing, while allowing students to explore the curriculum and culture of a specific dermatology program and demonstrate interest in a program.10 classically, learning dermatology has been achieved through clinical exposure and didactic teaching sessions, with varying use of online resources.9 adult learners, both in our course and in general, commonly enjoy the flipped classroom setting where self discussion skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 683 table 2 qualitative feedback from students and instructors for quality improvement student comments improve sustain …communication through zoom as a class is really difficult, might be easier if the class was broken into smaller groups… i liked that i could create my own schedule and study plan. incorporate patient care somehow, possibly just having the residents carry a device in clinic with a student(s) observing on zoom. i loved the grouping of the topics in each lecture and the pace that the elective was held at…. i entered my dermatology (in-person) elective much more comfortable with descriptions than i ever was before. i would have liked more opportunity to practice knowledge of the content formally, with say a qbank or another recommended resource. i enjoyed the interactive sessions led by residents as i was able to better practice what i had been learning and ensure that my knowledge and reasoning were correct. instructor comments improve sustain it's a great option in current times and is more convenient. however, it's hard to gauge if the information is a good level, and the students are more reluctant to participate. the convenience of online teaching is great, especially for busy residents. it was a great alternative, but i do not think it gives us the chance to really know the students. directed learning and online lectures substitute traditional didactics.11 they thrive when learning has a real-world application and can participate in course structure and learning goals due to motivation from intrinsic goals.8 continuing this style of learning in our current times can both reduce in-person sessions that must still adhere to pandemic-related restrictions and adapt to a learning style preferred by this current generation of learners. in our course, instructors were satisfied with content, convenience, and reaching a diverse student population, but highlighted challenges engaging students and gauging comprehension. an area of weakness identified by instructors was communication and interaction with students. possible causes include stressors posed by the pandemic, increased distractions at the home learning environment, and adapting to the new learning style. instructors did not see their students forming an online community, yet students felt they strengthened goals related to interpersonal and communication skills. this discrepancy suggests a difference in how students and instructors view interactions or an element of interaction outside the virtual classroom facilitating these connections. problembased learning and improvement showed lower satisfaction, suggesting a need for additional feedback in a virtual course.12 reducing class sizes by half (from ten to five students), adding in-class practice material, and immersing students in virtual health encounters may improve overall satisfaction. while limited by sample size, our course provided students with a satisfactory dermatology education that fulfilled acgme core competencies during the uncertain times of a pandemic and supports the possibility of a virtual platform to expand dermatology education. conflict of interest disclosures: none funding: penn state department of dermatology marks endowment corresponding author: shara chopra, bs, ba 1850 e park ave conclusion skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 684 state college, pa, 16803 phone: 814-404-1102 email: schopra1@pennstatehealth.psu.edu references: 1. edgar l, mclean s, hogan s et al. the milestones guidebook. accreditation council for graduate medical education (acgme). available at: https://www.acgme.org/portals/0/milestonesguid ebook.pdf [last accessed 5 december 2020]. 2. american academy of dermatology. basic dermatology curriculum. available at: https://www.aad.org/member/education/residents /bdc [last accessed 5 december 2020]. 3. regan, p. a., kirby, j. s. optimizing medical student dermatology education with the american academy of dermatology’s basic dermatology curriculum. skin the journal of cutaneous medicine, 2019;3(6), 443-446. 4. dhein cr, noxon jo, deykin a. teaching the didactic aspects of ophthalmology and dermatology using an off-site instructor. j vet med educ. 2005;32(1):57-67. 5. bolliger du, inan fa, wasilik o. development and validation of the online instructor satisfaction measure (oism). journal of educational technology & society, 2014;17(2):183-195. 6. tschannen-moran m, hoy aw. teacher efficacy: capturing an elusive construct. teaching and teacher education, 2001;17(7):783-805. 7. harris pa, taylor r, thielke r et al. research electronic data capture (redcap)--a metadatadriven methodology and workflow process for providing translational research informatics support. j biomed inform. 2009; 42: 377-381. 8. burge sm. learning dermatology. clin exp dermatol. 2004; 29: 337-40. 9. mccleskey pe, gilson rt, devillez rl. medical student core curriculum in dermatology survey. j am acad dermatol. 2009; 61: 30‐5. 10. adusumilli nc, kalen j, hausmann k, friedman aj. dermatology applicant perspectives of a virtual visiting rotation in the era of covid-19. journal of the american academy of dermatology. 2021;84(6):1699-701. 11. svoboda, s. a., swigert, a., nielson, c. b., motaparthi, k. inspired by covid-19 isolation: evolving educational techniques in dermatology residency programs. clinics in dermatology, 2021;39(1), 41-44. 12. meikleham a, hugo r. understanding informal feedback to improve online course design. european journal of engineering education. 2020 45:1, 4-21 mailto:schopra1@pennstatehealth.psu.edu https://www.acgme.org/portals/0/milestonesguidebook.pdf https://www.acgme.org/portals/0/milestonesguidebook.pdf https://www.aad.org/member/education/residents/bdc https://www.aad.org/member/education/residents/bdc skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 689 brief article dermatofibrosarcoma protuberans presenting as a subcutaneous cystic nodule chris logas, do1, austin dunn, do2, danielle lazarra, do1, justin rubin, do 1, eli saleeby md, brad p. glick, do1,3 1 larkin community hospital – palm springs campus, dermatology residency program, hialeah, fl 2 center for clinical and cosmetic research aventura, fl 3 glick skin institute, margate, fl dermatofibrosarcoma protuberans (dfsp) is a rare soft tissue tumor that was first described by derier and ferrand in 19241. it most often occurs on the trunk of young to middle aged patients and has an incidence of 4.1 per million adults accounting for 0.1% of all malignancies 2–4. it often presents as a slow growing, indurated plaque and progresses into a violaceous to red-brown firm nodule fixed to the skin with occasional reddish blue to reddish-yellow surrounding discoloration. tumors can measure from one centimeter upwards to several centimeters in diameter 2,5,6. although occurrence of dfsp is preceded by trauma in approximately 10% of cases, it is unclear if there is a direct correlation with development 4. dfsp is considered a lowgrade sarcoma and regarded as relatively benign with a low rate of metastasis (0.5%) and high 2-to-5-year survival rate (9297%)2,6. while dfsp has an overall good prognosis, the rate of recurrence is high (2050%), requiring lifelong surveillance of patients following diagnosis. surgical excision is the most common treatment but often proves incomplete due to the infiltrative growth pattern and fingerlike projections characteristic of the tumor. thus, mohs micrographic surgery (mms) is the preferred treatment to ensure a clear margin 2. we report a clinical case of a patient diagnosed with dfsp and subsequently treated with mms. a 41-year-old african american male with a past medical history significant for prediabetes and hypertension presented to the abstract a 41-year-old african american male complains of a painful cyst located on his right shoulder and lasting 2 for years. the specimen was excised and stained positive for cd34 and negative for sox10, confirming the diagnosis of dermatofibrosarcoma protuberans (dfsp). the initial specimen had positive extension at both the deep and lateral margins. complete removal of the tumor required 3 stages of mms resulting in a 10 cm x 7.6 cm final defect, extending to muscle. as demonstrated in this case, dfsp has an erratic growth pattern and requires meticulous histopathological examination to ensure clear margins. mms is the preferred method of treatment. cases of dfsp have high rates of recurrence and require regular follow-up for 3-5 years after treatment. introduction case report https://paperpile.com/c/10uaeo/zssn https://paperpile.com/c/10uaeo/kybp+gkdr+hdfe https://paperpile.com/c/10uaeo/l5sg+kybp+js8a https://paperpile.com/c/10uaeo/hdfe https://paperpile.com/c/10uaeo/js8a+kybp https://paperpile.com/c/10uaeo/kybp skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 690 clinic with a complaint of a cyst located on his right shoulder for 2 years (figure 1a). figure 1. a) initial presentation of a cystic nodule the nodule had been asymptomatic, but recently increased in size and became painful. this patient denied any associated symptoms including fever, chills, drainage, or increased warmth to the touch of lesion. physical exam revealed a large subcutaneous nodule about 2 cm in size, tender to palpation. the lesion was surgically excised a week later. histologically, the specimen was a markedly mesenchymal neoplasm occupying the reticular dermis, as well as the subcutis with invasion into the fat in a honeycombing fashion (figure 2). figure 2. h&e x10 after initial resection of tumor the neoplasm was extremely cellular with little intervening collagen. the cells were thin and filiform in shape, with slender, wavy nuclei, and in foci showed prominent whirling. the specimen stained positive for cd34 and negative for sox-10, confirming the diagnosis of dfsp (figure 3). figure 3. cd34 staining after initial resection of tumor the initial specimen had positive extension at both the deep and lateral margins. complete removal of the tumor required 3 stages of mms resulting in a 10 cm x 7.6 cm final defect, extending to muscle, (figure 1b). figure 1. b) surgical defect after 3 stages of mm histology of stages 1 and 2 exhibited a dense, cellular tumor proliferation composed of spindled fibroblasts intersecting collagen skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 691 bundles within the dermis and invading the subcutaneous fat. perineural invasion was not noted. the patient was referred to plastic surgeon for repair. a skin graft was determined to provide the best cosmetic and functional result. upon one month follow-up, the surgical defect and skin graft appeared well-healed. the patient underwent genetic, pet/ct imaging, and tumor marker testing which were all negative for any pathological abnormalities or metastatic disease. as in this case, diagnosis of dfsp may be challenging. a punch biopsy containing epidermis, dermis, and subcutaneous fat can lead to an accurate diagnosis, but excisional biopsy is the preferred diagnostic method 1. due to the erratic growth pattern of dfsp and the need for meticulous histopathological examination to ensure clear margins, mms is the preferred method of treatment4. recurrence rate decreased by 6.2% when using mms over wle (7.3% compared to 1.1%)4. a disadvantage of mms is that tumor cells can be confused with normal spindle cells of the dermis. cd34 staining can offer some assistance but is of variable use4 . a unique genetic transformation in dfsp allows for systemic therapy with tyrosine kinase inhibitors. approximately 90% of tumors are associated with the (17;22) translocation, which leads to formation of the col1a1-pdgfb fusion protein2. increased pdgfb expression leads to autocrine activation, tumor growth and development 4. imatinib targets the pdgf receptor, providing an alternative treatment option. in imatinib-resistant dfsp, other tyrosine kinase inhibitors such as sunitinib and sorafenib may be beneficial 2. adjuvant radiotherapy can be used if an excised tumor has positive margins and re-excision is not possible 1,2. due to the high rate of recurrence of dfsp, evaluation for metastasis and close, regular follow-up is critical when developing appropriate treatment plans. patients are recommended to have 3-to-6-month interval follow-ups for 3-5 years after initial diagnosis 4. conflict of interest disclosures: none funding: none corresponding author: austin dunn, do center for clinical and cosmetic research aventura, fl 2925 aventura blvd., suite 205 aventura, florida 33180 phone: (765) 808-3631 email: a.dunn@admcorp.com references: 1. allen, a., ahn, c. & sangüeza, o. p. dermatofibrosarcoma protuberans. dermatol. clin. 37, 483–488 (2019). 2. thway, k., noujaim, j., jones, r. l. & fisher, c. dermatofibrosarcoma protuberans: pathology, genetics, and potential therapeutic strategies. ann. diagn. pathol. 25, 64–71 (2016). 3. kreicher, k. l., kurlander, d. e., gittleman, h. r., barnholtz-sloan, j. & bordeaux, j. s. incidence and survival of dermatofibrosarcoma protuberans in the united states. journal of clinical oncology vol. 32 9037–9037 (2014). 4. acosta, a. e. & vélez, c. s. dermatofibrosarcoma protuberans. curr. treat. options oncol. 18, 56 (2017). 5. llombart, b. et al. guidelines for diagnosis and treatment of cutaneous sarcomas: dermatofibrosarcoma protuberans. actas discussion conclusion https://paperpile.com/c/10uaeo/zssn https://paperpile.com/c/10uaeo/hdfe https://paperpile.com/c/10uaeo/hdfe https://paperpile.com/c/10uaeo/hdfe https://paperpile.com/c/10uaeo/kybp https://paperpile.com/c/10uaeo/hdfe https://paperpile.com/c/10uaeo/kybp https://paperpile.com/c/10uaeo/zssn+kybp https://paperpile.com/c/10uaeo/hdfe mailto:a.dunn@admcorp.com http://paperpile.com/b/10uaeo/zssn http://paperpile.com/b/10uaeo/zssn http://paperpile.com/b/10uaeo/zssn http://paperpile.com/b/10uaeo/zssn http://paperpile.com/b/10uaeo/zssn http://paperpile.com/b/10uaeo/zssn http://paperpile.com/b/10uaeo/zssn http://paperpile.com/b/10uaeo/kybp http://paperpile.com/b/10uaeo/kybp http://paperpile.com/b/10uaeo/kybp http://paperpile.com/b/10uaeo/kybp http://paperpile.com/b/10uaeo/kybp http://paperpile.com/b/10uaeo/kybp http://paperpile.com/b/10uaeo/kybp http://paperpile.com/b/10uaeo/kybp http://paperpile.com/b/10uaeo/gkdr http://paperpile.com/b/10uaeo/gkdr http://paperpile.com/b/10uaeo/gkdr http://paperpile.com/b/10uaeo/gkdr http://paperpile.com/b/10uaeo/gkdr http://paperpile.com/b/10uaeo/gkdr http://paperpile.com/b/10uaeo/gkdr http://paperpile.com/b/10uaeo/hdfe http://paperpile.com/b/10uaeo/hdfe http://paperpile.com/b/10uaeo/hdfe http://paperpile.com/b/10uaeo/hdfe http://paperpile.com/b/10uaeo/hdfe http://paperpile.com/b/10uaeo/hdfe http://paperpile.com/b/10uaeo/hdfe http://paperpile.com/b/10uaeo/l5sg http://paperpile.com/b/10uaeo/l5sg http://paperpile.com/b/10uaeo/l5sg http://paperpile.com/b/10uaeo/l5sg http://paperpile.com/b/10uaeo/l5sg http://paperpile.com/b/10uaeo/l5sg skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 692 dermo-sifiliográficas (english edition) vol. 109 868–877 (2018). 6. van lee, c. b. et al. dermatofibrosarcoma protuberans re-excision and recurrence rates in the netherlands between 1989 and 2016. acta derm. venereol. 99, 1160–1165 (2019). http://paperpile.com/b/10uaeo/l5sg http://paperpile.com/b/10uaeo/l5sg http://paperpile.com/b/10uaeo/l5sg http://paperpile.com/b/10uaeo/js8a http://paperpile.com/b/10uaeo/js8a http://paperpile.com/b/10uaeo/js8a http://paperpile.com/b/10uaeo/js8a http://paperpile.com/b/10uaeo/js8a http://paperpile.com/b/10uaeo/js8a http://paperpile.com/b/10uaeo/js8a http://paperpile.com/b/10uaeo/js8a http://paperpile.com/b/10uaeo/js8a http://paperpile.com/b/10uaeo/js8a guselkumab in psoriasis patients with a history of malignancy: 5-year safety from voyage 1&2 andrew blauvelt,1 diamant thaçi,2 kim a papp,3 vincent ho,4 kamran ghoreschi,5 byung soo kim,6 megan miller,7 yaung-kaung shen,7 yin you,7 jenny yu,7 ya-wen yang,8 jeff crowley,9 peter foley10 1oregon medical research center, portland, or, usa; 2university of luebeck, luebeck, germany; 3k papp clinical research and probity medical research, waterloo, on, canada; 4department of dermatology and skin science, university of british columbia, vancouver, bc, canada; 5department of dermatology, venereology and allergology, charité – universitätsmedizin, berlin, germany; 6pusan national university hospital, busan, south korea; 7janssen research & development, llc, spring house/horsham, pa, usa; 8immunology global medical affairs, janssen pharmaceutical companies of johnson & johnson, horsham, pa, usa; 9bakersfield dermatology and skin cancer medical group, bakersfield, ca, usa; 10the university of melbourne, st. vincent’s hospital melbourne and probity medical research, skin health institute, carlton, vic, australia background/objective methods conclusions this poster was supported by janssen research and development, llc • originally presented at eadv’s 30th congress, virtual, september 29-october 2, 2021. presented at the winter clinical dermatology conference hawaii® (wc22), 14th-19th jan 2022. • malignancy is a potential safety concern for all immunomodulatory biologics. patients with a history of malignancy are often excluded from clinical trials, which limits the availability of safety data for biologics in this population1,2 • guselkumab (gus), an interleukin-23 p19 subunit inhibitor, is approved for the treatment of moderate to severe psoriasis and active psoriatic arthritis • voyage 1 and 2 were phase 3 studies that demonstrated the long-term efficacy and safety of gus in patients with moderate to severe psoriasis3,4 • these studies included a small number of patients with a history of malignancy (excluding non-melanoma skin cancer [nmsc]) at baseline with no evidence of recurrence for greater than 5 years prior to screening • this analysis examines malignancy and other serious adverse events (saes) reported in these patients through 5 years in voyage 1 and 2 patients with a history of malignancy at baseline • of 1721 gus-treated patients, 18 (1.0%) had a prior history of malignancy at baseline • mean (sd) exposure to gus during the voyage 1 or 2 study=184 (87) weeks; median (range)=225.5 (20-254) weeks saes other than malignancies • of 18 patients with a prior history of malignancy at baseline, 5 had saes other than malignancies nmsc events • from baseline to week 264, nmsc was reported in 2 of 18 patients with a prior history of malignancy • among 18 patients with a history of malignancy who were exposed to gus for up to 5 years there were: o 2 new primary malignancies (papillary breast carcinoma and invasive melanoma) o 1 recurrence of bronchial carcinoma confounded by exposure to adalimumab • this analysis did not identify any new safety concerns that would limit the long-term use of gus in patients with a history of malignancy • more patients and longer duration of follow-up are needed to better characterize the use of gus in patients with a history of malignancy results of these 18 patients, 3 experienced saes of malignancy while participating in voyage 1 or 2 for up to 5 years references 1. wong pkk, et al. curr rheumatol rep. 2018;20:64. 2. plachouri k-m, georgiou s. int j dermatol. 2019;58:1008-13. 3. reich k, et al. br j dermatol. 2021 jun 9. doi: 10.1111/bjd.20568. online ahead of print. 4. reich k, et al. j am acad dermatol. 2020;82:936-45. disclosures a. blauvelt: scientific adviser/investigator for abbvie, abcentra, aligos, almirall, amgen, arcutis, arena, aslan, athenex, boehringer ingelheim, bristol myers squibb, dermavant, ecor1, eli lilly, evommune, forte, galderma, incyte, janssen, landos, leo, novartis, pfizer, rapt, regeneron, sanofi genzyme, sun pharma, ucb, and vibliome. d. thaҫi: consultant/advisor for abbvie, almirall, beiersdorf, boehringer ingelheim, celgene, eli lilly, hexal ag, janssen-cilag, leo pharma, novartis, pfizer, sandoz, sanofi, and ucb; speaker for abbvie, almirall, celgene, eli lilly, hexal ag, janssen-cilag, medac pharma, novartis, pfizer, regeneron, sandoz, sanofi, schering-plough, and ucb; investigator for abbvie, celgene, eli lilly, glaxosmithkline, janssen-cilag, leo pharma, novartis, parexel, pfizer, regeneron, and ucb. k. papp: received clinical research grants/honoraria as consultant/speaker/investigator/scientific officer/advisory board member/steering committee member for abbvie, akros, amgen, anacor, arcutis, astellas, avillion, bausch health/valeant, baxalta, boehringer ingelheim, bristol myers squibb, can-fite, celgene, coherus, dermavant, dermira, dow, eli lilly, evelo, galapagos, galderma, genentech, gilead, gsk, incyte, janssen, kyowa hakko kirin, leo, medimmune, meiji seika pharma, merck (msd), merckserono, mitsubishi pharma, moberg pharma, novartis, pfizer, prcl research, regeneron, roche, sanofi-aventis/genzyme, sun pharma, takeda, and ucb. v. ho: advisory board participant, investigator, and/or speaker for abbvie, lilly, novartis, janssen, and sanofi. k. ghoreschi: research grants, or honoraria for participation in advisory boards, clinical trials, or as speaker for one or more of the following: abbvie, almirall, boehringer ingelheim pharma, bristol myers squibb, celgene, eli lilly, janssen-cilag, leo pharma, medac, novartis pharma, pfizer, and ucb pharma. b.s. kim: grants from abbvie, boehringer ingelheim, elililly, janssen, leo, novartis, regeneron, sanofi, and ucb. j. crowley: consultant/speaker/investigator for abbvie, lilly, novartis, janssen, regeneron, sanofi, sun pharma, ucb; consultant/investigator for dermira, arcutis; investigator for merck, pfizer, sandoz, mc2 therapeutics, verrica pharmaceuticals; consultant for boehringer ingelheim and bristol myers squibb. m. miller, y.-k. shen, y. you, j. yu: employees of janssen research & development, llc (a subsidiary of johnson & johnson), and own johnson & johnson stock/stock options. y.-w. yang: employee of janssen pharmaceutical companies of johnson & johnson; owns johnson & johnson stock/stock options. p. foley: received grant support, and/or served on advisory boards, and/or served as a consultant, and/or has received travel grants, and/or has served as a speaker for or received honoraria from abbvie, akaal, amgen, arcutis, argenx, aslan, astrazeneca, bms, boehringer ingelheim, botanix, celgene, celtaxsys, csl, cutanea, dermira, galderma, genesiscare, genentech, gsk, hexima, janssen, leo pharma, lilly, mayne pharma, medimmune, melaseq/geneseq, merck, novartis, pfizer, regeneron, reistone, roche, sanofi, sun pharma, ucb pharma, valeant, wintermute. • a descriptive analysis of saes of malignancies and other saes through week 264 was performed in gus-treated patients with a history of malignancy (excluding nmsc) at baseline o exposure to gus was calculated for these patients with a history of malignancy at baseline • patients who were diagnosed with a malignancy during the study (except ≤2 localized basal cell carcinomas) were required to discontinue study treatment figure 1. voyage 1 study design figure 2. voyage 2 study design ada = adalimumab; dbl = database lock; gus = guselkumab; pbo = placebo; pe = primary endpoint; r = randomization; se = secondary endpoint; q2w = every 2 weeks; q8w = every 8 weeks *the last dose of gus was administered at week 252; efficacy was evaluated through week 252. †safety was evaluated through week 264. *no further information is available about this sae. ada = adalimumab; dbl = database lock; gus = guselkumab; nonresponders nr < pasi 90; pbo = placebo; pasi = psoriasis area and severity index; pe = primary endpoint; q2w = every 2 weeks; q8w = every 8 weeks; r = randomization; responders r ≥ pasi 90; se = secondary endpoint *upon loss of ≥50% of improvement in pasi achieved at week 28 or at week 72 if prerequisite loss of pasi improvement was not observed, then reinitiate or initiate gus; †the last dose of gus was administered at week 252; efficacy was evaluated through week 252; ‡safety was evaluated through week 264. prior malignancies*,† • cervical, n=4 • melanoma, n=2 • kidney, n=1 • testicular, n=1 • prostate, n=4 • colon, n=1 • lung, n=1 • thyroid, n=1 • breast, n=2 • dermatofibrosarcoma, n=1 • rectal, n=1 *1 patient had a history of both kidney and prostate cancer. †4 patients (with a history of cervical cancer, kidney and prostate cancer, lung cancer, and thyroid cancer, respectively) received adalimumab during the active-comparator period of the study. patient 1 • history (hx) of prostate cancer (2007) • sae of metastatic invasive papillary breast cancer • investigator: sae not related to study medication patient 2 • hx of bronchial carcinoma (1997-2007) • sae of bronchial carcinoma recurrence with metastases • investigator: sae not related to study medication patient 3 • hx of prostate cancer (2010) • sae of invasive melanoma of the right forearm • investigator: sae not related to study medication patient 1: sae of metastatic breast cancer demographics & medical hx • white; male; usa; age 76 years; body mass index (bmi) 35.4 kg/m2 • prostate cancer, early coronary artery disease, hypertension (htn), psoriatic arthritis, hyperlipidemia, pulmonary mass, alcohol consumption • prior psoralen with ultraviolet a, topical treatment voyage 1 treatment • randomized to gus • received gus every 8 weeks (q8w) from week (w) 0-28 malignancy sae • right breast lump observed ~1 year prior to study entry • lump slowly enlarged and became tender • diagnosis on day 202: 2.7 cm subareolar right breast mass • gene mutation identification testing was negative • grade 3 infiltrating ductal carcinoma with focal micropapillary features • 2 of 6 lymph nodes positive for metastasis • recovered following right modified radical mastectomy patient 2: sae of recurrent bronchial carcinoma patient 3: sae of invasive melanoma demographics & medical hx • white; male; germany; age 57 years; bmi 36.6 kg/m2 • lung cancer, smoker (0.5 packs/day), family hx of cancer, benign prostatic hypertrophy, htn • prior methotrexate, ultraviolet b, and topical treatment demographics & medical hx • white; male; canada; age 71 years; bmi 31.9 kg/m2 • type i/ii skin; sun exposure from recreational activities (avid golfer) • prostate cancer, family hx of cancer, former smoker, alcohol consumption, hyperlipidemia • prior topical treatment voyage 2 treatment • randomized to adalimumab • received gus from w28-100 voyage 2 treatment • randomized to placebo • received gus at w16 and w20; rerandomized to placebo from w28-72 • open-label gus q8w from w72-180 • total gus exposure=161 weeks malignancy sae • right lower lobe lung carcinoma diagnosed on day 753 (stage ivb; ct4 n3 m1c) • tumor infiltration into middle lobe; exophytic tumor growth in lower lobe • poorly differentiated non-cornified squamous cell carcinoma, programmed death-ligand 1 negative • 3 supratentorial brain metastases • died of bronchial carcinoma ~4 months after study discontinuation malignancy sae* • right forearm invasive melanoma diagnosed on day 1139 • ulcerated depth=at least 0.7 mm; mitotic rate=3 cells/mm2 • margins involved; no lymphovascular invasion • had 2 basal cell carcinomas during study (left cheek, day 211; left ankle, day 1139) • recovered after surgical removal of melanoma age; race; sex; country; study prior malignancy treatment phase sae (day; treatment relatedness; outcome) 57 y; asian; f; korea; voy 2 cervical cancer gus gus • multiple fractures (day 141; not related; resolved) • subdural hemorrhage (day 141; not related; resolved) 57 y; white; f; germany; voy 2 breast cancer withdrawal withdrawal • noncardiac chest pain (day 204; not related; resolved) • herniated disc (day 231; not related; resolved) 64 y; white; f; spain; voy 2 breast cancer gus withdrawal • cardiac failure (day 127; not related; resolved) • respiratory failure (day 238; not related; resolved) 68 y; white; m; usa; voy 2 dermatofibrosarcoma protuberans gus gus (open-label) gus (open-label) • cellulitis (day 435; possible; resolved) • presyncope (day 1201; not related; not resolved) • chest injury (day 1378; not related; resolved) 59 y; white; f; usa; voy 1 cervical cancer gus (open-label) • cellulitis (day 1456; doubtful related; resolved) f=female; gus=guselkumab; hx=history; m=male; sae=serious adverse event; voy=voyage; y=years. age; race; sex; country; study prior malignancy treatment phase nmsc (location; study day; treatment relatedness; outcome) 71 y; white; m; canada; voy 2* prostate cancer withdrawal gus (open-label) • bcc (left cheek; day 211; not related; resolved) • bcc (left ankle; day 1139; not related; resolved) 72 y; white; m; usa; voy 2 rectal cancer gus gus (open-label) • bcc (left eyelid; day 394; not related; resolved) • sebaceous carcinoma (right eyelid; day 1168; possible; resolving) *this is the same patient diagnosed with invasive melanoma (right forearm) on day 1139. bcc=basal cell carcinoma; gus=guselkumab; m=male; nmsc=non-melanoma skin cancer; voy=voyage; y=years. skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 189 clinical management recommendations integrating genomic testing for melanoma into your practice nicholas brownstone, md1, danny zakria, md, mba2, mckenzie a. dirr, ba, bs3, yenn lu, ba4, darrell s. rigel, md, ms5 1 national society for cutaneous medicine, new york, ny 2 department of surgery, vanderbilt university medical center, nashville, tn 3 medical university of south carolina, charleston, sc 4 university of missouri, kansas city, kansas city, mo 5 department of dermatology, mount sinai icahn school of medicine, new york, ny melanoma is the most dangerous form of skin cancer and mortality is dependent upon stage of diagnosis. patients with a stage i melanoma will have a 97% 5-year survival rate versus a patient with a stage iv lesion will only have a 15% survival rate. therefore, early detection is critical as management is heavily affected by prognosis. given this relationship, accurate assessment of prognosis is critical for effectively managing melanoma. traditionally, tumor depth and other clinical and histological factors have been used to help predict the likelihood of metastasis and have ultimately been used as a proxy for survival1,2. while the american joint committee on cancer’s (ajcc) clinicopathological factors are effective at accurately assessing tumor stage, the majority of deaths still occur in early stage disease3. excluding stage iv patients, 80% of patients present with stage i disease yet 41% of deaths still occur in this population. this is due to the fact that while the overall survival percentage is higher for thin melanomas, the absolute number of mortalities is greatest for thin tumors4. furthermore, one study found pathological diagnostic discordance between thin invasive melanomas and melanoma in situ (mmis) when reviewed by an expert dermatopathologist5. in addition, the factors that have been traditionally used for prognosis, including tumor thickness and ulceration status, are somewhat subjective. for all of these reasons, it has been suggested that adding molecular information to the ajcc melanoma staging system could contribute to improved prognostic accuracy in melanoma patients6. recent advances in genomic technology have also led to earlier detection of melanoma and in some cases allowed the clinician to avoid an invasive biopsy altogether7 8. this clinical management guideline manuscript reviews how gene expression profiling (gep) can be used to improve the diagnosis and prognosis of melanoma and will offer guidance on effective integration into clinical practice using patient vignettes. introduction using genomics to assess prognosis skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 190 the 31-gep test is a clinical laboratory improvement amendments (clia) approved test that uses formalin-fixed, paraffinembedded tissue that requires no extra processing on behalf of the dermatologist or dermatopathologist. it identifies a genomic profile using a validated algorithm that identifies the likelihood of developing melanoma tumor recurrence or metastasis within 5 years. the test uses 28 genes and 3 control genes that are involved in many cellular processes associated with tumor progression and metastasis and assesses the net activity of the interplay between these genes9. the 31-gep test was developed with the goal of assessing the risk of melanoma recurrence independent from clinicopathologic factors. patients are risk stratified into class 1a meaning low risk of melanoma recurrence, 1b/2a for moderate risk or class 2b indicating a high risk of melanoma recurrence. approximately 85% of patients fall within class 1a (lowest risk category) or class 2b (highest risk category). through a more accurate assessment of prognosis, 31-gep can help guide management in the clinical setting. a patient with a low-risk result can be considered for lower frequency clinical follow up. a patient with a higher-risk result can be considered for closer monitoring and more aggressive intervention such as adjuvant therapy or advanced imaging. the 31-gep test has been validated in over 2,900 patients across 20 peer reviewed publications including validation/performance studies, prospective studies and clinical impact studies10, 11,12. physicians, nurse practitioners and physician assistants have been shown to use the results from this test to make more risk appropriate changes in their clinical management13,11. the 31-gep test can also guide decision making regarding sentinel lymph node biopsy (slnb) in melanoma patients. as per the national comprehensive cancer center (nccn) guidelines, if the risk of slnb positivity is less than 5%, slnb should not be recommended to patients, but if the risk is calculated to be greater than 10% then it should be discussed and offered to the patient. unfortunately the slnb false negative rate is significant, with some studies estimating it be as high as 17%14. moreover, the slnb procedure itself has morbidity including poor wound healing, infection and lymphedema. multiple studies have shown that the 31-gep test is able identify lower slnb positivity rates for class 1a patients and higher positivity rates for class 2b patients15,16,17. vetto et. al. demonstrated that for patients 55 years or older, the 31-gep test can identify a population with a low risk (<5%) of slnb positivity and a high risk (>10%) of slnb positivity18. when the test is applied to a t1t2 slnb eligible melanoma, a discussion regarding the potential avoidance of a slnb procedure in a class 1a patient (< 5% risk of positivity) is possible. conversely, the procedure could be offered to class 2b patients (> 10% risk of positivity). this management approach has the potential to result in an increase in the yield of slnb procedures, an avoidance of unnecessary surgical procedures in low-risk patients and a reduction in healthcare costs. importantly, this test is also covered by medicare. example 1 a 66-year-old female presents to your office for further management after a biopsy performed by a local family medicine physician. results of the biopsy show 31-gep test clinical examples skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 191 melanoma with breslow thickness of 0.6 mm. there is no ulceration or mitoses present. the patient has no history of melanoma but does a have a history of a previously treated basal cell carcinoma and actinic keratosis. the patient asks you about her prognosis and if she needs any further treatment. to help guide this decision, you order the 31-gep test on this patient’s biopsy specimen. the result of this test is a class 2b which indicates she is at high risk for recurrence and metastasis. based on this information you decide to alter your normal management regimen usually employed for a lesion of this thickness. you counsel the patient on the importance of being followed more frequently than you had originally planned and you also refer her to clinical oncology to evaluate the need for advanced imaging and adjuvant therapy. this example highlights a patient with traditionally low risk clinical tumor characteristics who has a high-risk tumor genetic profile and might therefore benefit from a more rigorous management regimen. example 2 a 30-year-old female patient presents to your office after her husband had noticed a changing pigmented lesion on her back. the patient has no past medical history and no history of skin cancer but did frequently use tanning beds throughout her college years. after taking a biopsy of the lesion, the report comes back a few days later with a 0.7 mm breslow thickness melanoma extending to the base of the specimen. since the actual breslow thickness is unknown, you decide to order the 31-gep test to help guide further management. the test shows a class 1a result. given this low-risk result, you can counsel the patient that she does not require more intensive monitoring and does not need any further imaging or adjuvant therapy. in this scenario, the 31-gep test helps guide management by demonstrating that the patient was at a low risk for metastasis or recurrence, even though the true breslow thickness could not be determined. example 3 a 68-year-old female patient returns to your office after having a biopsy proven melanoma detected in clinic the previous week. the patient’s melanoma has a breslow thickness of 1.1 mm, a mitotic rate of 1/mm2, positive ulceration but no other high-risk features. as per ajcc staging criteria alone, this patient would qualify as stage t2b which would predict her likelihood of slnb positivity to be >10%. given that alone, you would discuss and offer the procedure to this patient. however, you decide to apply the 31-gep test to the patient’s already processed biopsy specimen. you receive a report which indicates the patient has a class 1a result. based on this new information, the predicted slnb positivity rate is 2.9% and you can now confidently have an informed discussion with the patient on the low yield of the procedure. example 4 a 63-year-old male patient returns to your office after having a biopsy proven melanoma from his recent office visit. the patient’s melanoma has a breslow thickness of 0.7 mm and has no other high-risk features. as per the traditional staging criteria, this patient would qualify as stage t1a which would predict his slnb positivity to be less than 5%. therefore, you would not typically discuss and offer the procedure to this patient. however, you decide to apply the 31-gep test to the patient’s already processed biopsy specimen. you receive a report which indicates the patient has a skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 192 class 2b result. based on this new information, the predicted slnb positivity rate is 15.1% and you can now confidently have an informed discussion about the procedure’s benefits. the 2-gep test uses a noninvasive adhesive patch to sample a suspicious skin lesion to help classify pigmented lesions as melanoma or non-melanoma when dealing with clinically difficult cases19. this pigmented lesion assay analyzes two genes, linc (long intergenic non-protein coding rna 518) and prame (preferentially expressed antigen in melanoma). these two genes were chosen due to the fact that these were the best performing gene pairs, of an original 17 gene discriminatory set, when separating melanoma from nonmelanoma lesions with high levels of accuracy19. linc is a part of a cluster of regulatory rna molecules involved in melanoma proliferation and prame promotes tumor progression by interfering with retinoic acid receptor (rar) signaling. the negative predictive value of the 2-gep test was found to be greater than 99% in the real-world trust study. after analyzing over 5,000 patients, the 2-gep test reduced biopsies by approximately 85%20. the test has been well validated with 14 peerreviewed manuscripts demonstrating analytical validation, clinical validation and clinical utility. clinicians have been shown to follow the test guidance in over 98% of cases21,22. brouha et. al. demonstrated a close correlation between the genomic atypia and advanced histopathological atypia of melanoma, further validating the utility of the 2-gep test as a non-invasive method to detect melanoma8. a 54-year-old male is being evaluated for a chief complaint of a “suspicious lesion”. the patient has no personal history but does a have a family history of melanoma. he shows you a sharply demarcated, irregularly-shaped, 6 mm pigmented lesion on his left distal forearm which he thinks has been growing. however, clinical and dermoscopic exam reveals a mostly homogenous pigment pattern consistent with neighboring, smaller lesions. given these equivocal findings, you decide to apply the 2-gep test to evaluate the lesion for genomic atypia to help guide your decision to perform a biopsy. after applying the non-invasive skin patch and sending the specimen for analysis, you receive a report that linc and prame were both detected. given this additional information, you decide to perform a biopsy which resulted in a histopathological diagnosis of a 0.5mm, stage pt1a melanoma. the patient had a subsequent surgical excision with appropriate margins and has no signs of recurrence at his 6 month follow up and subsequent visits. melanoma is a life-threatening neoplasm where early detection along with appropriately timed intervention has the ability to significantly improve outcomes. however, practice gaps still exist for the diagnosis and treatment of melanoma given the challenges in defining high-risk subsets of lower-risk patients who may die from this cancer. furthermore, decisions to biopsy suspicious lesions are heavily dependent upon subjective visual exams. integrating the non-invasive 31-gep and 2-gep tests into clinical practice for assessing melanoma using genomics to assess diagnosis 2-gep test clinical example conclusion skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 193 diagnosis and prognosis has been shown to enhance accuracy. for these reasons, gene expression profiling technology is becoming an important adjunct in clinical practice to the standard of care for melanoma management. conflict of interest disclosures: dsr serves as a consultant for castle biosciences and dermtech funding: none corresponding author: nicholas brownstone, md melanoma fellow national society for cutaneous medicine new york ny email: nicholas@fred.health references: 1. mossbacher u, knollmayer s, binder m, steiner a, wolff k, pehamberger h. increased nuclear volume in metastasizing “thick” melanomas. j invest dermatol. 1996;106(3):437-440. doi:10.1111/15231747.ep12343580 2. breslow a. thickness, cross-sectional areas and depth of invasion in the prognosis of cutaneous melanoma. ann surg. 1970;172(5):902-908. 3. morton dl, thompson jf, cochran aj, et al. final trial report of sentinel-node biopsy versus nodal observation in melanoma. n engl j med. 2014;370(7):599-609. doi:10.1056/nejmoa1310460 4. more people die from thin melanomas than thick melanomas. accessed december 13, 2021. https://www.mdedge.com/internalmedicine/artic le/87682/melanoma/more-people-die-thinmelanomas-thick-melanomas 5. santillan aa, messina jl, marzban ss, crespo g, sondak vk, zager js. pathology review of thin melanoma and melanoma in situ in a multidisciplinary melanoma clinic: impact on treatment decisions. j clin oncol off j am soc clin oncol. 2010;28(3):481-486. doi:10.1200/jco.2009.24.7734 6. ferguson pm, gershenwald je, scolyer ra. staging of cutaneous melanoma: is there room for further improvement? jama netw open. 2018;1(1):e180086. doi:10.1001/jamanetworkopen.2018.0086 7. puglisi r, bellenghi m, pontecorvi g, pallante g, carè a, mattia g. biomarkers for diagnosis, prognosis and response to immunotherapy in melanoma. cancers. 2021;13(12):2875. doi:10.3390/cancers13122875 8. brouha b, ferris l, skelsey m, et al. genomic atypia to enrich melanoma positivity in biopsied lesions: gene expression and pathology findings from a large u.s. registry study. skin j cutan med. 2021;5(1):13-18. doi:10.25251/skin.5.1.3 9. gerami p, cook rw, wilkinson j, et al. development of a prognostic genetic signature to predict the metastatic risk associated with cutaneous melanoma. clin cancer res off j am assoc cancer res. 2015;21(1):175-183. doi:10.1158/1078-0432.ccr-13-3316 10. gastman br, zager js, messina jl, et al. performance of a 31-gene expression profile test in cutaneous melanomas of the head and neck. head neck. 2019;41(4):871-879. doi:10.1002/hed.25473 11. mirsky r, prado g, svoboda r, glazer a, rigel d. management decisions made by physician assistants and nurse practitioners in cutaneous malignant melanoma patients: impact of a 31-gene expression profile test. j drugs dermatol jdd. 2018;17(11):1220-1223. 12. keller j, schwartz tl, lizalek jm, et al. prospective validation of the prognostic 31gene expression profiling test in primary cutaneous melanoma. cancer med. 2019;8(5):2205-2212. doi:10.1002/cam4.2128 13. dillon ld, gadzia je, davidson rs, et al. prospective, multicenter clinical impact evaluation of a 31-gene expression profile test for management of melanoma patients. skin j cutan med. 2018;2(2):111-121. doi:10.25251/skin.2.2.3 14. durham ab, schwartz jl, lowe l, et al. the natural history of thin melanoma and the utility of sentinel lymph node biopsy. j surg oncol. 2017;116(8):1185-1192. doi:10.1002/jso.24765 15. schuitevoerder d, heath m, cook rw, et al. impact of gene expression profiling on decision-making in clinically node negative melanoma patients after surgical staging. j drugs dermatol jdd. 2018;17(2):196-199. 16. hsueh ec, debloom jr, lee j, et al. interim analysis of survival in a prospective, multicenter registry cohort of cutaneous melanoma tested with a prognostic 31-gene expression profile test. j hematol oncolj hematol oncol. 2017;10(1):152. doi:10.1186/s13045-017-05201 skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 194 17. vetto jt, hsueh ec, gastman br, et al. guidance of sentinel lymph node biopsy decisions in patients with t1-t2 melanoma using gene expression profiling. future oncol lond engl. 2019;15(11):1207-1217. doi:10.2217/fon-2018-0912 18. vetto jt, hsueh ec, gastman br, et al. guidance of sentinel lymph node biopsy decisions in patients with t1-t2 melanoma using gene expression profiling. future oncol lond engl. 2019;15(11):1207-1217. doi:10.2217/fon-2018-0912 19. gerami p, yao z, polsky d, et al. development and validation of a noninvasive 2-gene molecular assay for cutaneous melanoma. j am acad dermatol. 2017;76(1):114-120.e2. doi:10.1016/j.jaad.2016.07.038 20. skelsey m, brouha b, rock j, et al. noninvasive detection of genomic atypia increases real-world npv and ppv of the melanoma diagnostic pathway and reduces biopsy burden. skin j cutan med. 2021;5(5):512-523. doi:10.25251/skin.5.5.9 21. ferris lk, rigel ds, siegel dm, et al. impact on clinical practice of a non-invasive gene expression melanoma rule-out test: 12-month follow-up of negative test results and utility data from a large us registry study. dermatol online j. 2019;25(5):13030/qt61w6h7mn. 22. elmore jg, barnhill rl, elder de, et al. pathologists’ diagnosis of invasive melanoma and melanocytic proliferations: observer accuracy and reproducibility study. bmj. 2017;357:j2813. doi:10.1136/bmj.j2813 kim papp, md, phd,1 jacek c. szepietowski, md, phd, frcp (edin),2 leon kircik, md,3 darryl toth, md,4 lawrence f. eichenfield, md,5 seth b. forman, md,6 michael e. kuligowski, md, phd, mba,7 may e. venturanza, md,7 kang sun, phd,7 eric l. simpson, md, mcr8 introduction ● atopic dermatitis (ad) is a highly pruritic inflammatory skin disease1 ● the pathogenesis of ad involves janus kinases (jaks) acting downstream of proinflammatory cytokines and itch mediators2,3 ● ruxolitinib cream is a topical formulation of ruxolitinib, a selective inhibitor of jak1 and jak24 ● in two phase 3 randomized studies of identical design (true-ad1 [nct03745638] and true-ad2 [nct03745651]), ruxolitinib cream demonstrated anti-inflammatory activity with antipruritic action vs vehicle and was well tolerated in patients with ad4 (figure 1) figure 1. primary and key secondary endpoints at week 8 of the vehicle-controlled period in true-ad1 and true-ad2 15.1 true-ad1 true-ad2 true-ad1 true-ad2 true-ad1 true-ad2 true-ad1 true-ad2 24.6 15.4 9.5 **** 50.0 **** 56.0 *** 40.4 ** 21.0 **** 53.8 **** 62.1 **** 52.2 ** 22.3 7.6 14.4 16.3 19.1 **** 39.0 **** 51.5 **** 42.7 20.7 **** 51.3 **** 61.8 **** 50.7 25.6 0 10 20 30 40 50 60 70 iga-ts† easi-75 itch nrs4 promis 8b response‡ pr op or tio n of p at ie nt s, % (s e) vehicle 0.75% rux 1.5% rux easi-75, ≥75% improvement from baseline in eczema area and severity index score; iga-ts, investigator’s global assessment-treatment success; nrs4, ≥4-point improvement in itch numerical rating scale score from baseline; promis, patient-reported outcomes measurement information system; rux, ruxolitinib cream. ** p<0.01 vs vehicle; *** p<0.001 vs vehicle; **** p<0.0001 vs vehicle. † iga score of 0 or 1 and ≥2-point improvement from baseline. ‡ ≥6-point improvement in promis short form sleep disturbance score 8(b). objective ● to evaluate the long-term safety and disease control of ruxolitinib cream in patients with ad methods study design and patients ● eligible patients were aged ≥12 years with ad for ≥2 years and had an investigator’s global assessment (iga) score of 2 or 3 and 3%–20% affected body surface area (bsa), excluding scalp ● key exclusion criteria were unstable course of ad, other types of eczema, immunocompromised status, use of ad systemic therapies during the washout period and during the study, use of ad topical therapies (except bland emollients) during the washout period and during the study, and any serious illness or medical condition that could interfere with study conduct, interpretation of data, or patients’ well-being ● true-ad1 and true-ad2 had identical study designs (figure 2) – in both studies, patients were randomized (2:2:1) to 1 of 2 ruxolitinib cream strength regimens (0.75% twice daily [bid], 1.5% bid) or vehicle cream bid for 8 weeks of double-blind continuous treatment (vehicle-controlled [vc] period); patients were instructed to continue treating lesions even if they improved – patients on ruxolitinib cream subsequently continued treatment for 44 weeks (long-term safety [lts] period); patients initially randomized to vehicle were rerandomized 1:1 (blinded) to either ruxolitinib cream regimen ■ during the lts period, patients were instructed to treat skin areas with active ad only and stop treatment 3 days after clearance of lesions; patients were to restart treatment with ruxolitinib cream at the first sign of recurrence figure 2. study design • continuous treatment for 8 weeks • rescue treatment not permitted • treat as needed for 44 weeks • stop treatment 3 days after lesion clearance • rescue treatment not permitted vehicle-controlled period long-term safety period patients initially randomized to rux remain on their regimen patients on vehicle rerandomized 1:1 to 0.75% rux bid or 1.5% rux bid patients randomized 2:2:1 rux† visits every 4 weeks week 52day 1 week 8 recurrence of lesions clearance of lesions 1.5% rux bid (n=~240 in each study) 0.75% rux bid (n=~240 in each study) vehicle bid (n=~120 in each study) ad, atopic dermatitis; bid, twice daily; bsa, body surface area; rux, ruxolitinib cream. † patients self-evaluated recurrence of lesions between study visits and treated lesions with active ad (≤20% bsa). if lesions cleared between study visits, patients stopped treatment 3 days after lesion disappearance. if new lesions were extensive or appeared in new areas, patients contacted the investigator to determine if an unscheduled additional visit was needed. 1k. papp clinical research and probity medical research, waterloo, on, canada; 2department of dermatology, venereology and allergology, wroclaw medical university, wroclaw, poland; 3icahn school of medicine at mount sinai, new york, ny, usa; 4xlr8 medical research and probity medical research, windsor, on, canada; 5departments of dermatology and pediatrics, university of california san diego, san diego, ca, usa; 6forcare clinical research, tampa, fl, usa; 7incyte corporation, wilmington, de, usa; 8oregon health & science university, portland, or, usa assessments ● safety and tolerability assessments included the frequency of reported treatmentemergent adverse events (teaes), treatment-related adverse events, and adverse events (aes) leading to treatment discontinuation ● disease control was assessed by the proportion of patients who achieved no or minimal skin lesions (iga score of 0 or 1 [clear or almost clear skin]) and mean percentage of bsa affected by ad at each visit (every 4 weeks) during the lts period statistical analyses ● data were analyzed by descriptive statistics ● disease control data (iga 0/1 and bsa) are reported as observed results patients ● a total of 1249 patients were randomized in the vc period ● distribution of baseline demographics and clinical characteristics was similar across treatment groups (table 1) table 1. patient demographics and baseline clinical characteristics true-ad1 true-ad2 characteristic vehicle (n=126) 0.75% rux (n=252) 1.5% rux (n=253) vehicle (n=124) 0.75% rux (n=248) 1.5% rux (n=246) age, median (range), y 31.5 (12–82) 34.0 (12–85) 30.0 (12–77) 37.5 (12–82) 33.0 (12–81) 32.0 (12–85) female, n (%) 79 (62.7) 154 (61.1) 158 (62.5) 80 (64.5) 150 (60.5) 150 (61.0) race, n (%) white 85 (67.5) 171 (67.9) 177 (70.0) 85 (68.5) 174 (70.2) 178 (72.4) black 29 (23.0) 55 (21.8) 56 (22.1) 32 (25.8) 63 (25.4) 57 (23.2) asian 8 (6.3) 10 (4.0) 14 (5.5) 2 (1.6) 6 (2.4) 6 (2.4) other 4 (3.2) 16 (6.3) 6 (2.4) 5 (4.0) 5 (2.0) 5 (2.0) region, n (%) north america 88 (69.8) 176 (69.8) 176 (69.6) 84 (67.7) 166 (66.9) 165 (67.1) europe 38 (30.2) 76 (30.2) 77 (30.4) 40 (32.3) 82 (33.1) 81 (32.9) bsa, mean (sd), % 9.2 (5.1) 9.9 (5.4) 9.3 (5.2) 10.1 (5.8) 10.1 (5.3) 9.9 (5.4) easi, mean (sd) 7.4 (4.3) 8.2 (4.8) 7.9 (4.6) 8.2 (5.2) 8.1 (5.0) 7.8 (4.9) iga, n (%) 2 31 (24.6) 61 (24.2) 60 (23.7) 33 (26.6) 64 (25.8) 63 (25.6) 3 95 (75.4) 191 (75.8) 193 (76.3) 91 (73.4) 184 (74.2) 183 (74.4) itch nrs score, mean (sd) 5.1 (2.5) 5.1 (2.3) 5.2 (2.5) 5.1 (2.4) 5.2 (2.5) 4.9 (2.5) ≥4, n (%) 78 (61.9) 156 (61.9) 161 (63.6) 81 (65.3) 168 (67.7) 154 (62.6) duration of disease, median (range), y 17.9 (1.9–79.1) 14.1 (1.0–68.8) 16.0 (0–69.2) 15.9 (0.8–70.7) 15.9 (0.1–68.6) 16.6 (0–68.8) facial involvement, n (%)* 52 (41.3) 112 (44.4) 118 (46.6) 41 (33.1) 83 (33.5) 79 (32.1) number of flares in last 12 mo, mean (sd)* 9.4 (35.2) 5.3 (7.5) 6.0 (23.3) 5.1 (8.1) 5.1 (5.8) 5.9 (8.5) bsa, body surface area; easi, eczema area and severity index; iga, investigator’s global assessment; nrs, numerical rating scale; rux, ruxolitinib cream. * patient reported. ● in true-ad1, 542 patients entered the lts period, and 430 (79.3%) completed the study – the most common reasons for discontinuation were withdrawal by patient (n=49 [9.0%]) and lost to follow-up (n=41 [7.6%]) ● in true-ad2, 530 patients entered the lts period, and 401 (75.7%) completed the study – the most common reasons for discontinuation were withdrawal by patient (n=78 [14.7%]) and lost to follow-up (n=25 [4.7%]) ● the median (range) cumulative time off treatment due to lesion clearance was 91.0 (2–307) and 116.0 (2–286) days in true-ad1 for 0.75% and 1.5% ruxolitinib cream, respectively, and 126.0 (3–308) and 145.5 (2–312) days in true-ad2 ● among patients who achieved iga 0 at the end of the vc period, median time to first retreatment was 6.5 and 11.0 days in true-ad1 for 0.75% and 1.5% ruxolitinib cream, respectively, and 21.0 and 18.5 days in true-ad2 safety ● the safety profile of ruxolitinib cream in the lts period was consistent with the vc period ● ruxolitinib cream was well tolerated, and the frequency of application site reactions was low (table 2) table 2. adverse events in the lts period (pooled) n, % vehicle to 0.75% rux (n=101) vehicle to 1.5% rux (n=99) 0.75% rux (n=426) 1.5% rux (n=446) patients with teae 54 (53.5) 57 (57.6) 256 (60.1) 240 (53.8) patients with treatment-related ae 2 (2.0) 6 (6.1) 20 (4.7) 13 (2.9) patients who discontinued due to a teae 0 0 9 (2.1) 0 patients with serious teae 5 (5.0) 1 (1.0) 10 (2.3) 6 (1.3) ae, adverse event; lts, long-term safety; rux, ruxolitinib cream; teae, treatment-emergent adverse event. ● no clinically meaningful changes or trends in hematologic parameters were noted over the 52-week period ● no aes suggestive of a relationship to systemic exposure were observed ● the most common teaes (>2.0% in either ruxolitinib cream group) for the full 52-week study are shown in table 3 table 3. most common teaes for the 52-week study (pooled) teae, n (%)* 0.75% rux (n=601)† 1.5% rux (n=598)† upper respiratory tract infection 50 (8.3) 60 (10.0) nasopharyngitis 46 (7.7) 58 (9.7) headache 19 (3.2) 24 (4.0) bronchitis 16 (2.7) 20 (3.3) rhinitis 19 (3.2) 12 (2.0) atopic dermatitis 17 (2.8) 12 (2.0) influenza 8 (1.3) 18 (3.0) hypertension 16 (2.7) 11 (1.8) asthma 13 (2.2) 12 (2.0) sinusitis 17 (2.8) 8 (1.3) conjunctivitis 14 (2.3) 4 (0.7) lts, long-term safety; rux, ruxolitinib cream; teae, treatment-emergent adverse event; vc, vehicle controlled. * teae >2.0% in either rux cream group. † includes patients who received ≥1 dose of rux in the vc and/or lts period. ● exposure-adjusted teaes and application site reactions were lower for patients who applied ruxolitinib cream vs vehicle (table 4) table 4. exposure-adjusted teaes true-ad1 true-ad2 n (exposure-adjusted ir per 100 py) vehicle (n=126) 0.75% rux (n=300) 1.5% rux (n=300) vehicle (n=124) 0.75% rux (n=301) 1.5% rux (n=298) any teae 44 (251.4) 171 (75.2) 172 (72.9) 39 (223.0) 197 (91.9) 173 (75.2) any application site reaction 8 (45.7) 8 (3.5) 5 (2.1) 11 (62.9) 10 (4.7) 5 (2.2) ir, incidence rate; py, patient-year; teae, treatment-emergent adverse event. disease control ● the proportion of patients with clear or almost clear skin (iga 0/1) increased during the lts period with as-needed use of ruxolitinib cream (figure 3) ● the proportion of patients who achieved an iga score of 0/1 increased after switching from vehicle to either ruxolitinib cream strength in the lts period (figure 3) ● mean affected bsa decreased during the lts period with as-needed use of ruxolitinib cream (figure 4) ● affected bsa was substantially reduced after switching from vehicle to either ruxolitinib cream strength in the lts period (figure 4) figure 3. proportion of patients with clear or almost clear skin (iga 0/1) in the lts period 0 20 40 60 80 100 8 12 16 20 24 28 32 36 40 44 48 52 a) time, wk 76.9 76.3 vehicle to 0.75% rux vehicle to 1.5% rux 0.75% rux 1.5% rux vehicle to 0.75% rux vehicle to 1.5% rux 0.75% rux 1.5% rux 75.4 73.7 80.1 79.4 76.7 74.4 0 pa tie nt s w ith c le ar o r a lm os t cl ea r s ki n (ig a of 0 o r 1 ), % n 48 45 43 44 42 37 35 34 32 33 36 38 n 47 46 45 46 42 43 43 39 39 37 38 38 n 222 212 206 197 176 171 165 161 162 167 167 173 n 225 212 206 204 189 172 170 173 163 172 160 171 50 47 47 42 41 37 35 32 35 35 34 34 49 48 47 46 46 43 44 43 42 44 43 43 186 183 177 173 169 162 151 146 150 153 149 150 203 196 193 188 185 182 172 169 169 171 166 171 0 20 40 60 80 100 8 12 16 20 24 28 32 36 40 44 48 52 b) time, wk 0 pa tie nt s w ith c le ar o r a lm os t cl ea r s ki n (ig a of 0 o r 1 ), % n n n n true-ad1 true-ad2 iga, investigator’s global assessment; lts, long-term safety; rux, ruxolitinib cream. figure 4. affected bsa in the lts period 1.5 1.5 1.0 1.0 2.2 2.2 1.9 1.4 48 44 42 44 42 37 35 34 32 33 36 38 47 46 45 46 42 43 43 39 39 37 38 38 222 212 206 197 178 171 164 161 162 168 167 173 225 212 206 204 189 172 170 173 164 172 161 171 50 47 47 43 41 38 35 34 35 35 34 34 49 48 47 46 46 43 44 43 42 44 43 43 187 183 177 173 169 163 153 147 150 153 150 150 203 196 193 188 185 182 172 169 169 171 166 172 0 2 4 6 8 10 8 12 16 20 24 28 32 36 40 44 48 52 a) time, wk 0 m ea n to ta l a ffe ct ed b sa , % n n n n 0 2 4 6 8 10 8 12 16 20 24 28 32 36 40 44 48 52 b) time, wk 0 m ea n to ta l a ffe ct ed b sa , % n n n n true-ad1 true-ad2 vehicle to 0.75% rux vehicle to 1.5% rux 0.75% rux 1.5% rux vehicle to 0.75% rux vehicle to 1.5% rux 0.75% rux 1.5% rux bsa, body surface area; lts, long-term safety; rux, ruxolitinib cream. conclusions ● over 75% of patients who entered the lts period completed the study ● ruxolitinib cream was well tolerated over 52 weeks, with a consistent safety profile throughout the study period – the incidence of application site reactions was low ● disease control was observed with ruxolitinib cream monotherapy use as needed during the lts period – a high proportion of patients maintained clear or almost clear skin using ruxolitinib cream as needed – mean affected bsa decreased during the lts period – patients who previously applied vehicle exhibited disease control with ruxolitinib cream through achievement of clear or almost clear skin and reductions in affected bsa disclosures kp has received honoraria or clinical research grants as a consultant, speaker, scientific officer, advisory board member, and/or steering committee member for abbvie, akros, amgen, anacor, arcutis, astellas, bausch health/valeant, baxalta, boehringer ingelheim, bristol myers squibb, can-fite, celgene, coherus, dermira, dow pharmaceuticals, eli lilly, galderma, gilead, glaxosmithkline, incyte corporation, inflarx, janssen, kyowa hakko kirin, leo pharma, meiji seika pharma, merck (msd), merck serono, mitsubishi pharma, moberg pharma, novartis, pfizer, prcl research, regeneron, roche, sanofi-aventis/genzyme, sun pharmaceuticals, takeda, and ucb. jcs has served as an advisor for abbvie, leo pharma, menlo therapeutics, novartis, pierre fabre, and trevi; has received speaker honoraria from abbvie, eli lilly, janssen-cilag, leo pharma, novartis, sanofi genzyme, and sun pharma; and has received clinical trial funding from abbvie, almirall, amgen, galapagos, holm, incyte corporation, inflarx, janssen-cilag, menlo therapeutics, merck, novartis, pfizer, regeneron, trevi, and ucb. lk has served as an investigator, consultant, or speaker for abbvie, amgen, anaptys, arcutis, dermavant, eli lilly, glenmark, incyte corporation, kamedis, leo pharma, l’oreal, menlo therapeutics, novartis, ortho dermatologics, pfizer, regeneron, sanofi, sun pharma, and taro. dt has served as an investigator for abbvie, amgen, arcutis, astellas, astion, avillion, boehringer ingelheim, celgene, dermira, dow pharmaceuticals, ds biopharma, eli lilly, f. hoffmann-la roche ltd, galderma, glaxosmithkline, incyte corporation, isotechnika, janssen, leo pharma, merck, novartis, pfizer, regeneron, and ucb biopharma. lfe has served as an investigator, consultant, speaker, or data safety monitoring board member for abbvie, almirall, arcutis, asana, dermavant, eli lilly, forte biosciences, galderma, ichnos/glenmark, incyte corporation, janssen, leo pharma, novartis, ortho dermatologics, otsuka, pfizer, regeneron, and sanofi genzyme. sbf has received honoraria, clinical research grants, or fees as a consultant, speaker, advisory board member, and/or investigator for abbvie, aclaris therapeutics, asana biosciences, astrazeneca, athenex, celgene corporation, cutanea life sciences, eli lilly, incyte corporation, innovaderm research, novartis, pfizer, promius pharma, regeneron, ucb, valeant pharmaceuticals north america, and xbiotech. mek was an employee and shareholder of incyte corporation at the time of development of the original presentation. mev and ks are employees and shareholders of incyte corporation. els is an investigator for abbvie, eli lilly, galderma, kyowa hakko kirin, leo pharma, merck, pfizer, and regeneron and is a consultant with honorarium for abbvie, eli lilly, forte bio, galderma, incyte corporation, leo pharma, menlo therapeutics, novartis, pfizer, regeneron, sanofi genzyme, and valeant. acknowledgments the authors thank the patients, investigators, and investigational sites whose participation made the study possible. support for this study was provided by incyte corporation (wilmington, de, usa). writing assistance was provided by tania iqbal, phd, an employee of icon (north wales, pa, usa), and was funded by incyte corporation. references 1. langan sm, et al. lancet. 2020;396(10247):345-360. 2. bao l, et al. jakstat. 2013;2(3):e24137. 3. oetjen lk, et al. cell. 2017;171(1): 217-228. 4. papp k, et al. j am acad dermatol. 2021;85(4):863-872. long-term safety and disease control with ruxolitinib cream in atopic dermatitis: results from two phase 3 studies presented at the fall clinical dermatology conference las vegas, nv • october 21–24, 2021 to download a copy of this poster, scan code. skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 530 research letter laterality and site-specific distribution patterns of lentigo maligna and lentigo maligna melanoma gabrielle brody, bs1, katerina yale, md2, alora nguyen, bs2, margit juhasz, md, msc2, linda doan, md, phd2, natasha atanaskova mesinkovska, md, phd2 1 university of california, irvine, school of medicine, irvine, ca 2 university of california, irvine, department of dermatology, irvine, ca melanoma is known to have left-sided laterality and truncal predominance on the human body.1 the literature, however, has largely neglected to evaluate separate melanoma subtypes. specifically, the distribution and invasion patterns of lentigo maligna (lm) and lentigo maligna melanoma (lmm) have not been well described. this retrospective study aims to determine trends in the laterality and anatomical distribution of both lm and lmm. additionally, given the lack of invasion pattern analysis in previous studies, this trend in lm and lmm will be investigated to determine if certain sites demonstrate increased propensity for malignant invasion. according to 2016 data produced by the center for disease control and prevention and the national cancer institute, california is the leading state in both new melanoma cases and melanoma-related deaths abstract background: melanoma has been described to have preferential left-sided laterality on the human body. the distribution and invasion patterns of lentigo maligna (lm) and lentigo maligna melanoma (lmm) have not been well described. methods: this was a cross-sectional, retrospective study at a single, academic center. lm and lmm cases from 2008-2018 in the dermatopathology registry were analyzed. results: a total of 392 cases were included (241 lm and 151 lmm). there was no laterality preference overall. the only exception were neoplasms located on the head/neck, which showed a left-sided laterality. lm and lmm had the highest incidence on the head/neck, followed by upper extremities, trunk, then lower extremities. men had a higher incidence on the head/neck and trunk, while women had a higher incidence on the extremities. interestingly, the upper extremities and the right side of the female body had a higher propensity for invasive lesions. conclusion: while melanomas demonstrate preferential left-sided laterality, lm and lmm only share this pattern in respect to the head/neck region. our results complement previous study findings which characterize lm and lmm as a head/neck and upper extremity pathology. finally, our study suggests that certain body sites and laterality have an increased propensity for invasion. skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 531 nationwide.2 we chose to focus our study on this high impact patient population. table 1. clinical characteristics of histologic cases of lentigo maligna and lentigo maligna melanoma (%, n) men women total 63.5%, n=249 36.5%, n=143 n=392 laterality left 47.8%, 119 51.8%, 74 49.2%, 193 right 41.0%, 102 41.3%, 59 41.1%, 161 midline 8.0%, 20 4.2%, 6 6.6%, 26 not specified 3.2%, 8 2.8%, 4 3.1%, 12 biopsy site head/neck 58.2%, 145 35.0%, 50 49.7%, 195 scalp 9.6%, 24 2.8%, 4 7.1%, 28 face 33.7%, 84 28.7%, 41 31.9%, 125 ears 5.6%, 14 0.7%, 1 3.8%, 15 neck 9.2%, 23 2.8%, 4 6.9%, 27 upper extremities 20.5%, 51 33.6%, 48 25.3%, 99 upper extremities 20.5%, 51 32.2%, 46 24.7%, 97 hands 0.0%, 0 1.4%, 2 0.5%, 2 lower extremities 2.4%, 6 18.2%, 26 8.2%, 32 lower extremities 2.4%, 6 18.2%, 26 8.2%, 32 feet 0.0%, 0 0.0%, 0 0.0%, 0 buttocks 0.0%, 0 0.0%, 0 0.0%, 0 trunk 18.9%, 47 13.3%, 19 16.8%, 66 back of trunk 10.4%, 26 4.2%, 6 8.2%, 32 front of trunk 8.4%, 21 9.1%, 13 8.7%, 34 genitalia 0.0%, 0 0.0%, 0 0.0%, 0 invasion lm 63.9%, 159 57.3%, 82 61.5%, 242 lmm 36.1%, 90 42.7%, 61 38.5%, 151 lm = lentigo maligna, lmm = lentigo maligna melanoma for this retrospective, cross-sectional study, the university of california, irvine medical center dermatopathology database was utilized to investigate patterns of lesion distribution of lm and lmm cases from 2008-2018. lm and lmm had an anatomical distribution of 49.7% head/neck, 25.3% upper extremities, 16.8% trunk, and 8.2% lower extremities (table 1). men demonstrated a higher incidence on the head/neck and trunk, while women showed a higher incidence on the upper and lower extremities. interestingly, the upper extremities of women were found to have a higher proportion of invasive cases to superficial cases compared to other body sites (lmm:lm ratio: 1.40 upper extremities vs 0.39 head/neck vs 0.63 lower extremities vs 0.90 trunk, p=0.0226). men did not share this relationship (p=0.1318). similar to previous studies, our study observed a significant left-sided laterality for the head/neck region (59.1% left, p=0.0178) (table 2).3 the leading theory for the apparent left-sided distribution of melanoma is attributed to driving. a driver positioned in the left seat is exposed to 20 times the uv radiation on the left side of the face compared to the right.4 however, this same left sided laterally has been reported in locations such as the uk, where drivers are positioned on the right side of the vehicle.5 given this discrepancy, the etiology behind this left-sided laterality is likely more complex than behavioral patterns, and possibly involve complex intrinsic factors. numerous aspects of embryogenesis are known to occur in an asymmetric fashion.6 perhaps asymmetry in neural crest cell migration and distribution may play a role in the sidedness of melanoma. finally, neither side of the body showed a higher proportion of invasive cases (lmm) (p=0.1115). when analyzing women separately, however, there were significantly more invasive cases on skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 532 the right side of the body (lmm:lm ratio 1.36 right vs 0.48 left vs 0.50 midline, p=0.0257). the observed sex differences in the distribution pattern of lm and lmm support previous studies with similar findings in superficial spreading and nodular melanomas specifically, as well as studies that did not distinguish between subclassifications.7 this strengthens the evidence that lm and lmm share the same sex-specific site-dependent preferences table 2. distribution of lm and lmm as dependent on site and laterality (%, n) left right midline not specified head and neck 51.8%, 101 35.9%, 70 7.7%, 15 4.6%, 9 upper extremities 45.5%, 45 54.6%, 54 0.0%, 0 0.0%, 0 lower extremities 59.4%, 19 40.6%, 13 0.0%, 0 0.0%, 0 trunk 42.4%, 28 36.4%, 24 16.7%, 11 4.6%, 3 found in other forms of melanoma. the main limitation of this study is that it was a singleinstitution study, thus limiting the sample size and demographic population. this research would benefit from future multiinstitution studies to further confirm the generalizability of these results across demographic populations. these findings update the current understanding of the anatomical distribution and invasion patterns of lm and lmm and should help increase suspicion of left-sided lesions on the head/neck of the general population, trunk of men, and extremities of women. conflict of interest disclosures: none funding: none corresponding author: natasha a. mesinkovska md, phd department of dermatology university of california, irvine 843 health sciences road, hewitt hall 1001 irvine, ca 92697 phone: 949-824-7103 fax: 949-824-8954 email: natashadermatology@gmail.com references: 1. paulson kg, iyer jg, nghiem p. asymmetric lateral distribution of melanoma and merkel cell carcinoma in the united states. j am acad dermatol. 2011;65(1):35-39. doi:10.1016/j.jaad.2010.05.026 2. u.s. cancer statistics working group. u.s. cancer statistics data visualizations tool, based on november 2018 submission data (1999-2016): u.s. department of health and human services, centers for disease control and prevention and national cancer institute. www.cdc.gov/cancer/dataviz. accessed july 2, 2019. 3. dores gm, huycke mm, devesa ss. melanoma of the skin and laterality. j am acad dermatol. 2011;64(1):193-195; author reply 195-6. doi:10.1016/j.jaad.2010.06.062 4. moehrle m, soballa m, korn m. uv exposure in cars. photodermatol photoimmunol photomed. 2003;19(4):175-181. doi:10.1034/j.16000781.2003.00031.x 5. gorman m, hart a, mathew b. a left-sided prevalence of lentigo mal3igna: a uk based observational study and review of the evidence. dermatol res pract. 2015;2015:1-6. doi:10.1155/2015/310270 6. levin m. left-right asymmetry in embryonic development: a comprehensive review. mech dev. 2005;122(1):3-25. doi:10.1016/j.mod.2004.08.006 7. cho e, rosner ba, colditz ga. risk factors for melanoma by body site. cancer epidemiol biomarkers prev. 2005;14(5):1241-1244. doi:10.1158/1055-9965.epi-04-0632 mailto:natashadermatology@gmail.com skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 265 original research the top 100 most cited articles on hidradenitis suppurativa surav m. sakya,1 david r. hallan,2 sage gee,1 monica rizk,1 justin brooke1 and joslyn s. kirby3 1school of medicine, penn state college of medicine, hershey, pa 2department of neurosurgery, penn state college of medicine, hershey, pa 3department of dermatology, penn state milton s hershey medical center, hershey, pa hidradenitis suppurativa (hs), or acne inversa, is a devastating chronic inflammatory follicular skin disease that usually starts after puberty.1 hs primarily affects folds of the body, including the axilla, groin, inframammary, and anogenital regions. there is an average of 7.2-year delay in hs diagnosis leading to delays in effective treatment.2 substantial research has explored associations between hs and environmental factors and comorbidities.1-3 the pathophysiology of hs is not entirely elucidated, but much has been learned recently.3,4 there are multiple treatment modalities, though none are consistently curative.5,6 currently, there are increasing number of clinical trials on hs, and with all abstract background: hidradenitis suppurativa (hs) is a chronic condition that requires prompt diagnosis and treatment. to date, no bibliometric analysis on hs exists. analyzing the top 100 citations is important to understand the characteristics of the most influential studies in the hs research landscape, and to guide future research. objective: to analyze the top 100 most cited articles on hs using bibliometric analysis. methods: searches within scopus and web of science using "hidradenitis suppurativa" and "acne inversa" were conducted on may 14th, 2020. after excluding non-original articles, data for the top 100 articles were analyzed using r-studio and bibliometrix. five independent reviewers identified study topic and design. results: the top 100 most cited articles on hs were published between 1982 and 2017 with an average of 128.3 citations. the top research topic and design were treatment (40 articles) and randomized controlled trials (9), respectively. 2011 had the highest number of publications (9), and the 2012 article by gregor b. e. jemec had the highest citations (439). these articles were from 14 different countries with the united states and denmark as top countries. 27 journals published these articles with the british journal of dermatology (bjd) as the top journal. denmark had the greatest outside country collaborations. conclusions: the results of our study showed that hs research is steadily growing with greatest support from the bjd. there is a focus on treatments in hs research with the united states and european countries leading the way. however, greater worldwide research of hs is needed. introduction skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 266 the research being conducted on hs, evaluating research trends using bibliometric analysis can inform future directions. bibliometric analysis is defined as a statistical evaluation of published scientific articles and is a tool used to evaluate research published on a certain topic.7 this quantitative study can provide useful information about contributions made by various authors, countries, institutions, and journals which can be useful in facilitating future research collaborations. important quantitative information can be learned to understand the progress and trends of research in the field of medicine.8 bibliometric analyses have been performed for rosacea, psoriasis, and melanoma.9-12 however, hs, a devastating disease for patients, has not been studied to date. in this study, we identified and analyzed the top 100 most cited articles on hs to evaluate the characteristics of the most impactful published hs research articles. data sources a search of all databases and journals accessible within elsevier's scopus and thomson reuter's web of science from inception was performed on may 14th, 2020. a second search was performed on june 14th, 2020 to identify total number of publications for additional data and comparison. document search was performed using the boolean query "hidradenitis suppurativa" and "acne inversa" and was made without restrictions. from the search results, meta-analyses, systematic reviews, guidelines, letters, book chapters, notes, editorials, short surveys, conference papers, and news items were excluded. the remaining original publications from the databases were combined and sorted, and the 100 most cited papers were included. (figure 1) data collection data extracted from scopus included first author name and country of origin, corresponding author name and country of origin, journal name, and year of journal publication. additional data was abstracted by five investigators (ss, dh, sg, mr, jb), which included: study design and study topic. study design was abstracted and categorized as: “case reports/case-series,” “cohort/case control/cross-sectional studies,” or “randomized controlled trials (rcts).” study topic was categorized based on the article’s main conclusion: “clinical features/diagnosis,” “epidemiology,” “pathogenesis/pathophysiology,” or “treatment.” all research topics and designs were reviewed independently by five reviewers with consensus reached for all 100 articles. the bradford zone comprising three zones (zones 1, 2 and 3) was obtained as a measure of journal productivity.13 data analysis data analysis was performed using r-studio (r-studio, boston, ma) and bibliometrix (università degli studi di napoli federico ii, naples, italy), according to the methods described in bibliometrix: an r-tool for comprehensive science mapping analysis.14 graphs and tables were created, and basic descriptive statistics were calculated using microsoft excel (microsoft corporation, redmond, wa). article analysis figure 1 shows the results of the queries. the top 100 most cited articles were published between 1982 and 2017 and methods results skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 267 figure 1. workflow for 100 citations data extraction mean age was 15.4 years old from the first day of publication (table s1). the mean total and annual citations per article were 128.3 and 10.58, respectively. the top research topic was treatment (40%), followed by epidemiology (32%), pathogenesis/pathophysiology (20%), and clinical features/diagnosis (8%). the most frequent article design was cohort/case control/cross-sectional studies (84%), followed by rcts (9%), case reports/caseseries (7%) (table 1). the top five most cited articles are listed in table 2. most of these articles were categorized as epidemiology and cohort/case control/crosssectional studies, for their topic and design, respectively. furthermore, most of the top five highly cited articles were published in the journal of the american academy of dermatology. the years with the highest number of top 100 articles were: 1996 (7), 2007 (5), 2009 (7), 2010 (6), 2011 (9), 2012 (6), 2013 (5), 2014 (7), and 2016 (5) (figure 2). over a 3-year interval, the most prolific periods for top 100 articles were 2009 to 2011 (22), followed closely by 2012 to 2014 (18). journal analysis the top 100 articles related to hs were published in 27 different journals. the top five journals contributed two-thirds (n=65) of the top 100 articles. the british journal of dermatology had the highest number of articles (n=28) while the journal of the american academy of dermatology had the second highest (n= 19). the 27 journals that published the top 100 hs articles were separated into three bradford zones. zone 1 includes the british journal of dermatology and journal of the american academy of dermatology, representing the top two core journals having the largest publishing productivity among the top 100 citations. four journals in bradford zone 2 were dermatology, archives of dermatology, skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 268 table 1. top 100 citations main characteristics timespan (years) 19822017 number of publications per year 1982-1984 1985-1987 1988-1990 1991-1993 1994-1996 1997-1999 2000-2002 2003-2005 2006-2008 2009-2011 2012-2014 2015-2017 2018-2020 2 7 5 1 9 5 6 5 11 22 18 9 0 research topic clinical features/diagnosis epidemiology pathogenesis/pathophysiology treatment 8 32 20 40 research design case reports/case-series cohort/case control/cross-sectional studies randomized controlled trials 7 84 9 sources (journals) 27 mean years from publication 15.4 mean total citations per publication 128.3 mean annual citations per publication 10.58 total references 2030 total authors 382 mean authors per document* 3.82 mean co-authors per document** 5.18 *calculated as total number of unique authors divided by total number of articles **calculated as total number of authors divided by total number of articles jama dermatology, and journal of the european academy of dermatology and venereology, representing the second highest publishing productivity. the remaining 21 journals were assigned to zone 3, which included journals with the lowest publishing productivity. countries and collaborations a total of 14 countries participated in publishing the retrieved articles. denmark (2808) had the greatest share of citations followed by the united states (usa) (2268), the united kingdom (1417), and france (1414) (table 3). for the usa, only 15.8% of the articles had co-authors from different countries, and for denmark, only 11.8%. for the usa, approximately 84% of articles were published by domestic authors presented as percentage of single country publication (scp). on the other hand, approximately 33% of articles produced by researchers from france (n=9) and greece (n=3) had coauthors from different countries. for the top 10 active countries, a total of 13 (15.7%) articles were considered multiple country publication (mcp) while 69 (84.3%) of articles were considered scp (table 3). authors and affiliations a total of 382 authors contributed to the top 100 most cited articles on hs. analysis of the authors regardless of their authorship order showed that gregor b. e. jemec from the university of copenhagen in denmark published the greatest number of the most cited articles (n=21), followed by jurr boer (n=10) from deventer hospital in the netherlands, errol p. prens (n=9) from erasmus medical center in the netherlands, and hessel h. van der zee (n=8) from erasmus medical center in the netherlands. most of the corresponding authors were from the usa (n=19) and denmark (n=17) (table 3). the frequency distribution of author productivity in hs is out of 382 authors. 316 authors (82.7%) contributed to just one article. 46 authors (12%) contributed to two articles, and five authors (1.3%) contributed to three articles. all articles on hs per year a total of 1629 original articles on hs were published between 1939 and 2020 (82 years). there have been 22.63 articles published per year. 850 articles have been published from 2015 to the capture date, which represents 52.1% of all the published skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 269 table 2. top 5 most cited articles in hs rank title year journal name total citations total citations per year 1 hidradenitis suppurativa16 2012 new england journal of medicine 439 48.78 2 prevalence and factors associated with hidradenitis suppurativa: results from two case-control studies22 2008 journal of the american academy of dermatology 355 27.31 3 the prevalence of hidradenitis suppurativa and its potential precursor lesions 1996 journal of the american academy of dermatology 316 12.64 4 objective scoring of hidradenitis suppurativa reflecting the role of tobacco smoking and obesity 2009 british journal of dermatology 288 24.00 5 infliximab therapy for patients with moderate to severe hidradenitis suppurativa: a randomized, double-blind, placebo-controlled crossover trial20 2010 journal of the american academy of dermatology 252 22.91 figure 2. number of top 100 hs articles per year hs articles over the past 82 years. the largest percentage increase in articles was from 2014 to 2015 where there was a jump from 55 to 90 published articles. the greatest number of articles was published in 2019 (243 articles), and 158 articles have been published so far in 2020 (figure 3). the top 100 citations were published between 1982 and 2017 (36 years); reflecting a more recent trend of influential hs research. the majority of the top 100 publications (60%) were published in the 1 1 2 3 2 2 3 1 1 1 7 2 3 2 3 1 2 3 3 5 3 7 6 9 6 5 7 2 5 2 0 1 2 3 4 5 6 7 8 9 10 1 9 8 2 1 9 8 3 1 9 8 5 1 9 8 6 1 9 8 7 1 9 8 8 1 9 9 0 1 9 9 3 1 9 9 4 1 9 9 5 1 9 9 6 1 9 9 8 1 9 9 9 2 0 0 0 2 0 0 1 2 0 0 2 2 0 0 3 2 0 0 5 2 0 0 6 2 0 0 7 2 0 0 8 2 0 0 9 2 0 1 0 2 0 1 1 2 0 1 2 2 0 1 3 2 0 1 4 2 0 1 5 2 0 1 6 2 0 1 7 number of articles per year from 1982 to 2017 discussion skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 270 table 3. bibliometric features of top articles by country country total citations average article citations corresponding authors scp mcp mcp ratio denmark 2808 165 17 15 2 0.118 usa 2268 119 19 16 3 0.158 united kingdom 1417 142 10 8 2 0.2 france 1414 157 9 6 3 0.333 netherlands 1173 117 10 8 2 0.2 germany 890 127 7 7 0 0 sweden 403 101 4 4 0 0 greece 294 98 3 2 1 0 poland 261 130 2 2 0 0 switzerland 167 167 1 1 0 0 spain 141 141 1 1 0 0 ireland 128 128 1 1 0 0 india 82 82 1 1 0 0 canada 78 78 1 1 0 0 figure 3. number of published hs articles by 4-year intervals from 1939 to 2020 (current) most recent 12-year period between 2006 and 2017 and similarly, there was a notable increase starting in 2013 of an increase in all hs publications. szepietowski et al. found a similar increase in overall articles published on hs in pubmed after 2013, which is consistent with our data.2 this increase in all and top 100 publications coincides with the founding of the hs foundation in 2005. this may have contributed to the increase in publications through grants and a network of collaborators.2,15 of the 100 most cited articles, only 20 articles were classified as “pathogenesis/pathophysiology.” 243 158 0 20 40 60 80 100 120 140 160 180 200 220 240 260 1 9 3 6 1 9 4 0 1 9 4 4 1 9 4 8 1 9 5 2 1 9 5 6 1 9 6 0 1 9 6 4 1 9 6 8 1 9 7 2 1 9 7 6 1 9 8 0 1 9 8 4 1 9 8 8 1 9 9 2 1 9 9 6 2 0 0 0 2 0 0 4 2 0 0 8 2 0 1 2 2 0 1 6 2 0 2 0 # o f a rt ic le s year total number of published original hs articles by 4-year-interval from 1939 to 2020 skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 271 furthermore, jemec mentioned in his 2012 hs article that the pathogenesis of hs remains unclear; hs is a disease characterized by sebaceous gland atrophy, lymphocytic infiltration, pilosebaceous unit hyperkeratosis and formation of granulomas with hair follicle destruction.16 a more recent article by goldburg et al. in 2020 confirms the complexity and lack of clarity of hs pathogenesis with the addition of tnf-alpha and il-17 as key cytokines involved.17 even with multiple suggestive theories for the pathogenesis of hs, without true understanding of the disease pathophysiology, research in development of diagnostic tests and treatment options may be stagnated.18,19 after analyzing the 100 top cited articles by research topic, 40 out of 100 papers were related to treatments. within treatments, there were 9 rcts. the increased number of research articles regarding treatment may be associated with introduction of new pharmacotherapy options for hs. many of the articles are focused on the new surge of biologics, such as tnf-alpha inhibitors, which have been studied in dermatological conditions with rheumatology overlap. grant et al. had the highest cited article under treatment showing the efficacy and tolerability of infliximab as a treatment option for hs, which is a breakthrough in hs management.20 this study provided an important landmark trial of infliximab as a treatment, which is still currently used as a medical therapy option today. kimball et al. in 2012, the second highest cited article under treatment, conducted a phase 2 trial with 154 patients and showed promising benefits of adalimumab in moderate-tosevere hs. this led to two phase 3 trials completed in early 2014 called pioneer i and ii with bigger cohorts. the article was published in 2016 and is the second highest annually cited article.21 interestingly, epidemiology was a second highest study topic. the number one article was prevalence and factors associated with hidradenitis suppurativa: results from two case-control studies by revuz et al. this retrospective case control study showed hs had a strong association with smoking and obesity, two important risk factors that are clinically relevant to hs management today.22 on the other extreme, clinical features and diagnosis had the lowest articles. this may be due to the “obliteration by incorporation” phenomenon. this occurs over time because the findings may become common knowledge and as a result do not get appropriately cited. many important articles not cited within the top 100 may have been incorporated into hs common knowledge.12,23 furthermore, 86 different corresponding authors from 14 countries were represented, illustrating the worldwide prevalence of hs and the collaborations around the world. gregor b. e. jemec from the university of copenhagen in denmark remains the most influential figure in the hs research landscape. overall, the usa and europe are leaders in hs research. the usa and europe may be leaders in hs research because there is a higher burden of hs. hs prevalence ranges between 0.03% and 4% worldwide, but a meta-analysis by phan et al. in 2020 shows that prevalence of hs is highest in europe at 0.8% while the usa is at 0.2%.24-26 limitations the top 100 citations highlight hs research over the last 40 years, but it is important to note that many important articles exist outside of the top 100. these articles may represent growth trends in research, but this analysis may bias toward older articles that have had more time to accumulate citations.12,27 furthermore, although both skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 272 scopus and wos were searched, their indices do not contain every article ever published. it is likewise difficult to determine whether there were articles missed due to search limitations. the total publications data from 1939-2020 capture articles outside of the top 100, but fail to recognize the influence of the studies, which the top 100 citations show. to our knowledge, this is the first worldwide bibliometric study on hs. our study found that hs research has experienced notable growth in the last five years. gregor b. e. jemec from the university of copenhagen in denmark is most influential because he not only started the hs foundation in 2005, but also is the most prolific author in hs research. moreover, the british journal of dermatology houses the greatest number of these top 100 articles. the clinical trials with adalimumab remain highly cited each year. the prominent focus of hs research are biological treatments and studies on the reduction of quality of life as demonstrated by the top cited articles. given the financial, psychological and emotional burden of hs, inter-country collaboration among the top active researchers found in this study is encouraged. the quality and measurement of scientific progress is not solely based on pure number of citations. it is about the research itself in the top 100 citations that made its lasting impact on the hs research community and the patients suffering from hs. conflict of interest disclosures: j.s.k.: abbvie: consultant, speaker, advisory board (honoraria), chemocentryx, incyte, novartis, ucb: consultant (honoraria) the rest of authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or nonfinancial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript. funding: none corresponding author: surav m. sakya, bs 80 university manor east hershey, pa 17033 phone: 860-303-9727 email: surav.sakya@gmail.com references: 1. alikhan a, hocker tlh. review of dermatology. elsevier-health sciences division; 2017. 2. szepietowski jc, matusiak l. hidradenitis suppurativa: the disease which stimulates researchers and clinicians. dermatology. 2020;236(1):5-7. 3. alikhan a, sayed c, alavi a, et al. north american clinical management guidelines for hidradenitis suppurativa: a publication from the united states and canadian hidradenitis suppurativa foundations: part i: diagnosis, evaluation, and the use of complementary and procedural management. j am acad dermatol. 2019;81(1):76-90. 4. widlund h. notch signaling. cell signaling technology. published 2012. accessed. 5. alikhan a, sayed c, alavi a, et al. north american clinical management guidelines for hidradenitis suppurativa: a publication from the united states and canadian hidradenitis suppurativa foundations. journal of the american academy of dermatology. 2019;81(1):76-90. 6. hendricks aj, hsiao jl, lowes ma, shi vy. a comparison of international management guidelines for hidradenitis suppurativa. dermatology. 2019:1-16. 7. thompson df, walker ck. a descriptive and historical review of bibliometrics with applications to medical sciences. pharmacotherapy. 2015;35(6):551-559. 8. glänzel w, moed hf. journal impact measures in bibliometric research. scientometrics. 2002;53(2):171-193. 9. wu jj, choi ym, marczynski w. the 100 most cited psoriasis articles in clinical dermatologic conclusion skin may 2021 volume 5 issue 3 copyright 2021 the national society for cutaneous medicine 273 journals, 1970 to 2012. j clin aesthet dermatol. 2014;7(10):10-19. 10. berlinberg a, bilal j, riaz ib, kurtzman djb. the 100 top-cited publications in psoriatic arthritis: a bibliometric analysis. int j dermatol. 2019;58(9):1023-1034. 11. wang y, zhang h, fang r, tang k, sun q. the top 100 most cited articles in rosacea: a bibliometric analysis. j eur acad dermatol venereol. 2020. 12. joyce cw, sugrue cm, joyce km, kelly jl, regan pj. 100 citation classics in the melanoma literature: a bibliometric analysis. dermatol surg. 2014;40(12):1284-1298. 13. venable gt, shepherd ba, loftis cm, et al. bradford's law: identification of the core journals for neurosurgery and its subspecialties. j neurosurg. 2016;124(2):569-579. 14. aria m, cuccurullo c. bibliometrix: an r-tool for comprehensive science mapping analysis. journal of informetrics. 2017;11(4):959-975. 15. egeberg a, gislason gh, hansen pr. risk of major adverse cardiovascular events and allcause mortality in patients with hidradenitis suppurativa. jama dermatology. 2016. 16. jemec gbe. hidradenitis suppurativa. new england journal of medicine. 2012. 17. goldburg sr, strober be, payette mj. hidradenitis suppurativa: epidemiology, clinical presentation, and pathogenesis. j am acad dermatol. 2020;82(5):1045-1058. 18. parati g. antihypertensive therapy in 2014: linking pathophysiology to antihypertensive treatment. nat rev cardiol. 2015;12(2):77-79. 19. howes od, mcguire pk, kapur s. understanding pathophysiology is crucial in linking clinical staging to targeted therapeutics. world psychiatry. 2008;7(3):162-163. 20. grant a, gonzalez t, montgomery mo, cardenas v, kerdel fa. infliximab therapy for patients with moderate to severe hidradenitis suppurativa: a randomized, double-blind, placebo-controlled crossover trial. journal of the american academy of dermatology. 2010. 21. kimball ab, okun mm, williams da, et al. two phase 3 trials of adalimumab for hidradenitis suppurativa. new england journal of medicine. 2016. 22. revuz je, canoui-poitrine f, wolkenstein p, et al. prevalence and factors associated with hidradenitis suppurativa: results from two casecontrol studies. j am acad dermatol. 2008;59(4):596-601. 23. garfield e. 100 citation classics from the journal of the american medical association. jama. 1987;257(1):52-59. 24. jemec gb, kimball ab. hidradenitis suppurativa: epidemiology and scope of the problem. j am acad dermatol. 2015;73(5 suppl 1):s4-7. 25. phan k, charlton o, smith sd. global prevalence of hidradenitis suppurativa and geographical variation—systematic review and meta-analysis. biomedical dermatology. 2020;4(1):2. 26. alavi a, anooshirvani n, kim wb, coutts p, sibbald rg. quality-of-life impairment in patients with hidradenitis suppurativa: a canadian study. am j clin dermatol. 2015;16(1):61-65. 27. loonen mp, hage jj, kon m. plastic surgery classics: characteristics of 50 top-cited articles in four plastic surgery journals since 1946. plast reconstr surg. 2008;121(5):320e-327e. skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 551 brief article the goeckerman regimen as an effective treatment modality for checkpoint inhibitor dermatoses nicholas brownstone, md1, daniel d. cummins, ba1, jocelyn gandelman md1, tina bhutani md1, wilson liao md1 1 university of california san francisco, department of dermatology, san francisco, ca the development of immune checkpoint inhibitors has been a major breakthrough in cancer therapy. despite their benefits, these agents are frequently associated with cutaneous side effects1. here, we report the effective use of the goeckerman regimen in the treatment of an evolving immune checkpoint inhibitor dermatosis. the patient is a 67-year-old male who was diagnosed with mesothelioma in april 2015 and was started on pembrolizumab (200 mg iv every 6 weeks) in october 2015 at another institution. in july 2016, he developed a non-specific rash described in oncology records as: desquamation and induration on his extremities and crusting and fissuring of his hands. this improved with holding pembrolizumab and use of triamcinolone ointment. in august 2016 he re-started pembrolizumab. one month later, he developed an eruption described in outside oncology records as having well demarcated morphology and fissuring concerning for a psoriasiform dermatitis. pembrolizumab was held and he was treated with 75 mg of prednisone with subsequent taper and triamcinolone ointment with partial improvement. in december 2016 his pembrolizumab was discontinued due to persistent skin rash and hospitalization for adrenal insufficiency secondary to pembrolizumab. approximately four months after his last dose of pembrolizumab, in april 2017, the patient first presented to university of california, san francisco, department of abstract the development of immune checkpoint inhibitors has been a major breakthrough in cancer therapy. here, we report the effective use of the goeckerman regimen in the treatment of an evolving immune checkpoint inhibitor dermatosis. the patient is a 67-year-old male who was diagnosed with mesothelioma in april 2015 and was started on pembrolizumab presenting with subsequent skin eruptions (psoriasiform dermatitis and bullous disease). he received eight months of goeckerman therapy at university of california, san francisco, psoriasis and skin treatment center. within days of starting goeckerman therapy, he had rapid improvement in his skin lesions along with a reduction in pruritus. the goeckerman regimen is further discussed as a novel treatment method for checkpoint inhibitor dermatoses. introduction case report skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 552 dermatology given persistence of his rash. he had well defined erythematous papules and plaques with silvery scale involving approximately 20% body surface area consistent with a psoriasiform dermatitis (figure 1). figure 1. presentation of psoriasiform dermatitis after 14 doses of pembrolizumab. the bilateral arms demonstrated well demarcated erythematous papules and plaques with overlying silvery scale. a skin biopsy was obtained at this time and revealed lichenoid psoriasiform dermatitis with cytotoxicity (figure 2). the unique histological characteristics from this biopsy were as follows: thin band-like infiltrate of lymphocytes (some enlarged) and melanophages, and exocytosis of many lymphocytes into the surface epithelium that are coupled with scattered necrotic keratinocytes in outer epidermal layers along with a band of parakeratosis laced with serum. the decision to start goeckerman therapy was based on the persistence of his rash and the previous failure of topical and oral steroids. figure 2. psoriasiform epidermis with parakeratosis in the stratum corneum above a thin band-like infiltrate of lymphocytes and melanophages, with exocytosis of lymphocytes into the surface epithelium. a few scattered necrotic keratinocytes are noted as well in the epidermis. he received eight months of goeckerman therapy at university of california, san francisco, psoriasis and skin treatment center (ucsf pstc) which is a “day-care” outpatient phototherapy center equipped to treat patients with the goeckerman regimen by a trained nursing staff. after eight months he noticed significant improvement with only residual plaques on his legs. however, he was also noted to have tense bullae twice, at sites unaffected by his psoriasiform dermatitis, during the treatment regimen. he was positive for bullous pemphigoid (bp) antibodies 180 and 230 on enzyme-linked immunoassay (elisa) blood test, but his skin biopsy was negative on direct immunofluorescence (dif). this eruption cleared with triamcinolone ointment. he restarted pembrolizumab in march 2020, approximately three years after his last dose, given radiologic evidence of mesothelioma progression and after six doses developed a severely pruritic eruption. the patient again presented to the skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 553 uscf pstc in late july 2020, with generalized, pink plaques with a violaceous hue involving approximately 60% body surface area (figure 3). figure 3. well defined erythematous papules coalescing into plaques covering approximately 60% bsa with several tense bullae with serosanguinous fluid and superficial erosions atop the plaques. there were a few scattered erosions on his back and left knee and two tense bullae filled with serosanguinous fluid on the proximal right upper arm. at this time skin biopsy showed a sub-epidermal vesicle with a few lymphocytes and eosinophils in the papillary dermis which was consistent with bp. there was also positive dif with linear junctional deposition of igg and c3. bullous pemphigoid antibodies bp 180 and 230 were also positive at a higher titer than previously. pembrolizumab was held. he started the next day on goeckerman therapy. this treatment was selected given his prior response to goeckerman therapy and also to avoid a systemic agent which may have complicated his cancer treatment. given the possible risk of precipitating bullae with phototherapy, the decision was made to first initiate a cool-down period with intense topical therapy only and to hold phototherapy. within days of starting goeckerman therapy, he had rapid improvement in his skin lesions along with a reduction in pruritus. his itch level was greatly reduced from a 9 out of 10 to 1 out of 10 in this time period with sustained response. six weeks after treatment initiation his skin was clear with no new blisters while on goeckerman treatment (figure 4). he discontinued goeckerman treatment after approximately two months total of treatment and with discontinuation had recurrence of skin blistering approximately two months later, which again resolved with goeckerman therapy (without phototherapy). as of this writing, he has completed an additional 23 days of goeckerman therapy with resolution of blisters and near resolution of rash. figure 4. six weeks after starting goeckerman therapy demonstrating clear skin with postinflammatory hyperpigmentation and with no new bullae the therapeutic use of immune checkpoint inhibitors is rapidly increasing given their unique mechanism of action and ability to treat advanced cancers. these agents include pd-1 inhibitors, such as pembrolizumab, and pd-l1 inhibitors. it is not surprising that cutaneous toxicities (ircaes) represent one of the most frequent immune-related adverse events, as the etiology of many types of dermatitis are the result of overactive t-cells. this case is unique in that the patient developed two discussion skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 554 different pathological morphologies (psoriasiform dermatitis and bullous pemphigoid) while on the same treatment and that the psoriasiform dermatitis, on histology, had characteristics of a cytotoxic reaction commonly seen in deficiency dermatitides and hiv-associated photodermatitis. these histological characteristics were as follows: thin bandlike infiltrate of lymphocytes (some enlarged) and melanophages, and exocytosis of many lymphocytes into the surface epithelium that are coupled with scattered necrotic keratinocytes in outer epidermal layers along with a band of parakeratosis laced with serum. there are several different methods for treating ircaes which may depend on the severity of the presentation. treatment for psoriasiform dermatitis induced by immune checkpoint inhibitors includes high potency topical corticosteroids, vitamin d3 analogues, narrowband ultraviolet b phototherapy, and if lesions persist, retinoids or biologics2. the goeckerman regimen, consisting of exposure to ultraviolet b (uvb) light and application of crude coal tar (cct), was first introduced in 1925 for psoriasis. based on the safety and efficacy of the therapy, the goeckerman regimen is an excellent treatment modality for any patient with moderate to severe psoriasis, eczema, and other severe pruritic and/or inflammatory skin conditions3. one case report has even successfully documented the goeckerman regimen in the treatment of eruptive keratoacanthomas and lichenoid dermatitis due to pembrolizumab4. goeckerman therapy, to the authors’ knowledge, has never been reported as treating bp and a psoriasiform dermatitis due to an immune checkpoint inhibitor. our patient rapidly improved with goeckerman therapy which reduced his itch level from 9 out of 10 to 1 out of 10 and cleared the erythematous plaques and papules with no new blister formation. his positive response was maintained for two months while enrolled in therapy. his blisters have recurred off therapy but have briskly responded to repeat goeckerman therapy. there have been a few case reports and case series regarding the development of bullous disease in psoriasis patients treated with both uva and uvb phototherapy5,6,7,8,9. in a series of 7 patients with psoriasis who subsequently developed pemphigus, 30% had been treated with phototherapy7. pearson et. al. presented 3 cases of psoriasis patients presenting with bp induced by the goeckerman regimen8. it is hypothesized that the reduced barrier function of the diseased psoriatic epidermis combined with the irritant effects of coal tar and uv light, together with a low-grade immunological basement membrane zone insult may precipitate blister formation in an otherwise subclinical bp process9. however, no clear mechanistic link or association has been described in large scale studies. given the fact that bp may have been induced by pembrolizumab and exacerbated by uvb phototherapy, the decision was made to subsequently withhold phototherapy when the patient re-presented to goeckerman therapy in march 2020. in conclusion, goeckerman therapy may present a safe, rapid and effective method for checkpoint inhibitor dermatoses. conflict of interest disclosures: none funding: none corresponding author: conclusion skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 555 nicholas brownstone, md clinical research fellow psoriasis and skin treatment center department of dermatology university of california, san francisco 515 spruce street san francisco, ca 94118 email: nickbrownstone34@gmail.com references: 1. collins lk, chapman ms, carter jb, samie fh. cutaneous adverse effects of the immune checkpoint inhibitors. curr probl cancer. 2017;41(2):125-128. doi:10.1016/j.currproblcancer.2016.12.001 2. totonchy mb, ezaldein hh, ko cj, choi jn. inverse psoriasiform eruption during pembrolizumab therapy for metastatic melanoma. jama dermatol. 2016;152(5):590592. doi:10.1001/jamadermatol.2015.5210 3. gupta r, debbaneh m, butler d, et al. the goeckerman regimen for the treatment of moderate to severe psoriasis. j vis exp. 2013;(77). doi:10.3791/50509 4. crow ld, perkins i, twigg ar, et al. treatment of pd-1/pd-l1 inhibitor–induced dermatitis resolves concomitant eruptive keratoacanthomas. jama dermatol. 2020;156(5):598-600. doi:10.1001/jamadermatol.2020.0176 5. albergo rp, gilgor rs. delayed onset of bullous pemphigoid after puva and sunlight treatment of psoriasis. cutis. 1982;30(5):621-624. 6. suwarsa o, herlina l, sutedja e, dharmadji h, hindritiani r, gunawan h. concurrence of bullous pemphigoid and psoriasis: a case report. serbian journal of dermatology and venereology. 2018;10:124-128. doi:10.2478/sjdv-2018-0018 7. zhang x, mao x, theresia c, et al. pemphigus associated with psoriasis vulgaris: a retrospective study of seven patients and a review of the literature. acta dermatovenerol croat. 2018;26(3):226-232. 8. person jr, rogers rs. bullous pemphigoid and psoriasis: does subclinical bullous pemphigoid exist? br j dermatol. 1976;95(5):535-540. doi:10.1111/j.1365-2133.1976.tb00865.x 9. robinson jk, baughman rd, provost tt. bullous pemphigoid induced by puva therapy. is this the aetiology of the acral bullae produced during puva treatment? br j dermatol. 1978;99(6):709-713. doi:10.1111/j.13652133.1978.tb07067.x mailto:nickbrownstone34@gmail.com skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 122 research letter trends in medicare reimbursement within dermatology: 2011-2021 kyle lauck md1, quoc-bao nguyen md, mba2,3, adelaide a. hebert, md2,3,4 1 department of internal medicine, uthealth mcgovern medical school, houston, tx 2 department of dermatology, md anderson cancer center, houston, tx 3 department of dermatology, uthealth mcgovern medical school, houston, tx 4 department of pediatrics, uthealth mcgovern medical school, houston, tx recently, the centers for medicare and medicaid services (cms) have emphasized increased reimbursement for evaluation and management services (e/m) with compensatory cuts in procedural services. to date, a paucity of data exists examining reimbursement for e/m and procedural services within dermatology.1 this was a longitudinal analysis of reimbursement rates through time for common services, both e/m and procedural, performed by dermatologists to ascertain if trends were similar to other fields studied to date.2-5 using the physician/supplier procedure summary (psps), a cms database which tracks medicare part b claims per year, an extraction of the 20 most common health care procedure coding system (hcpcs) codes billed by a dermatologist was performed (table 1). an additional extraction of ten common e/m service codes billed in dermatology was extracted. using the cms medicare physician fee schedule (mpfs) look-up tool, which contains reimbursement for hcpcs codes through time, reimbursement rates for the extracted hcpcs codes were tabulated for the years 2011-2021. the consumer price index for medical care was then used to adjust nominal reimbursement to real 2021 us dollars. statistical analyses were accomplished with microsoft excel. trends were evaluated using linear regression with a significance level of p of 0.05 or below. for a comprehensive index of reimbursement rates from 2011-2021 please see supplemental table 1. without adjusting for inflation, reimbursement for all services analyzed increased 18.3%. when adjusted for inflation, average reimbursement declined by 9.57%. twenty two of thirty services decreased in reimbursement. reimbursement for e/m codes specifically decline by 8.34% when adjusted for inflation. seven out of ten e/m codes experienced a decrease. reimbursement for the 20 most common procedural codes decreased by 10.80% when adjusted for inflation. fifteen out of twenty codes declined in reimbursement (table 2). the inflation adjusted decline in reimbursement seen here parallels the average declines in other specialties including plastic and reconstructive surgery (14%), general surgery (24%), neurosurgery (26%), ophthalmology (26%), and otolaryngology (38%).2-5 e/m services make up a large portion of total payments to dermatologists, and inflation-adjusted skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 123 decline in e/m services from 2011-2021 is noteworthy. limitations of this study include that some codes change over time. psps did not contain hcpcs codes charged 10 or fewer times in a given locality, potentially underestimating the total submitted services rendered. extrapolation to general populations is difficult when only examining medicare reimbursement which did not include individuals with supplemental medicare plans nor individuals with private insurance. however a relative strength is longitudinal nature of this assessment, involving a decade of data attesting to the status of dermatology e/m and surgical services within medicare. the average decrease in reimbursement for all services and procedures examined here parallels other specialties in trend but is smaller in magnitude of decline. this decrease was demonstrated in both e/m and procedural services. future studies may reveal the impact of these trends on providers, practices, and patients. table 1. common services performed by a dermatologist in 2019 common services performed by a dermatologist in 2019 20 most common procedures hcpcs code procedure description 2019 submitted services 2019 reimbursement 17003 destruction of premalignant lesion add-on 14,861,990 $5.77 17000 destruction of premalignant lesion 4,518,895 $66.67 11102 tangential biopsy of skin 2,502,134 $100.91 17110 destruction of benign lesion. 1,697,547 $112.80 11103 tangential skin biopsy add-on 1,112,055 $54.42 95044 allergy patch testing 867,223 $5.77 17004 destruction of premalignant lesion add-on 682,436 $155.33 96910 photochemotherapy with uv-b 342,824 $116.77 13132 complex repair (cheeks, chin, mouth, neck, axillae, genitalia, hands, feet) 268,622 $492.29 17262 destruction of malignant lesion 238,580 $180.56 11104 punch biopsy of skin lesion 229,473 $126.86 12032 intermediate repair 210,625 $311.74 11900 intralesional injection 193,506 $55.50 77401 radiation treatment delivery 191,286 $25.23 11602 excision of malignant lesion 177,174 $254.44 skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 124 13121 complex repair (scalp, arm, legs) 169,546 $441.84 96900 ultraviolet light therapy 165,762 $21.98 77280 set radiation therapy field 155,304 $282.55 11301 shave skin lesion 0.6-1.0 cm 141,373 $122.53 69100 biopsy of external ear 118,656 $100.55 evaluation and management hcpcs code procedure description 2019 submitted services 2019 reimbursement 99201 office/outpatient visit new patient (10 minutes) 57,709 $46.49 99202 office/outpatient visit new patient (20 minutes) 649,072 $77.48 99203 office/outpatient visit new patient (30 minutes) 870,984 $109.92 99204 office/outpatient visit new patient (45 minutes) 35,726 $166.86 99205 office/outpatient visit new patient (60 minutes) 2,008 $209.75 99211 office/outpatient visit established patient (5 minutes) 40,616 $23.07 99212 office/outpatient visit established patient (10 minutes) 1,519,979 $45.77 99213 office/outpatient visit established patient (15 minutes) 6,103,195 $75.32 99214 office/outpatient visit established patient (25 minutes) 2,404,351 $110.28 99215 office/outpatient visit established (40 minutes) 23,336 $147.76 table 2. nominal vs. inflation adjusted changes in medicare reimbursement 2011 to 2021 top 20 most common procedures unadjusted reimbursement reimbursement adjusted for inflation with medical care cpi hcpcs code description 2011 2021 percent change pvalue 2011 2021 percent change p-value 17003 destruction of premalignant lesion add-on $7.14 $6.63 -7.14% 0.131 $9.35 $6.63 -29.06% 0.007 17000 destruction of premalignant lesion $79.51 $67.34 -15.31% <0.001 $104.07 $67.34 -35.30% <0.001 11102 tangential biopsy of skin $102.27 $106.42 4.06% 0.609 $133.87 $106.42 -20.50% <0.001 17110 destruction of benign lesion. $108.39 $116.19 7.20% 0.002 $141.88 $116.19 -18.10% <0.001 11103 tangential skin biopsy add-on $32.62 $54.08 65.79% 0.001 $42.70 $54.08 26.66% 0.037 95044 allergy patch testing $6.12 $5.58 -8.82% 0.016 $8.01 $5.58 -30.34% <0.001 17004 destruction of premalignant lesion add-on $171.92 $169.23 -1.56% 0.181 $225.03 $169.23 -24.80% <0.001 96910 photochemotherapy with uv-b $69.31 $122.13 76.21% <0.001 $90.72 $122.13 34.62% 0.009 13132 complex repair (cheeks, chin, mouth, neck, axillae, genitalia, hands, feet) $576.24 $491.30 -14.74% 0.023 $754.27 $491.30 -34.86% <0.001 17262 destruction of malignant lesion $171.92 $182.49 6.15% <0.001 $225.03 $182.49 -18.91% <0.001 11104 punch biopsy of skin lesion $102.27 $133.29 30.33% <0.001 $133.87 $133.29 -0.43% 0.658 12032 intermediate repair $302.05 $316.13 4.66% 0.002 $395.37 $316.13 -20.04% <0.001 11900 intralesional injection $55.38 $57.57 3.95% 0.053 $72.49 $57.57 -20.58% <0.001 77401 radiation treatment delivery $25.48 $43.97 72.57% 0.027 $33.35 $43.97 31.84% 0.347 11602 excision of malignant lesion $242.25 $253.67 4.71% 0.001 $317.09 $253.67 -20.00% <0.001 13121 complex repair (scalp, arm, legs) $438.64 $445.59 1.58% 0.474 $574.15 $445.59 -22.39% <0.001 96900 ultraviolet light therapy $20.73 $23.73 14.47% 0.023 $27.13 $23.73 -12.55% <0.001 77280 set radiation therapy field $188.91 $289.61 53.31% <0.001 $247.27 $289.61 17.12% 0.062 11301 shave skin lesion 0.6-1.0 cm $91.74 $127.71 39.21% 0.002 $120.08 $127.71 6.35% 0.857 skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 125 69100 biopsy of external ear $102.95 $101.54 -1.37% 0.112 $134.76 $101.54 -24.65% <0.001 evaluation and management unadjusted reimbursement reimbursement adjusted for inflation with medical care cpi hcpcs code description 2011 2021 percent change pvalue 2011 2021 percent change p-value 99201 office/outpatient visit new patient (10 minutes) $41.11 46.56* 13.26% <0.001 53.81066 47.01* -12.63% <0.001 99202 office/outpatient visit new patient (20 minutes) $71.01 73.97 4.17% <0.001 92.94806 73.97 -20.42% <0.001 99203 office/outpatient visit new patient (30-44 minutes) $102.95 113.75 10.49% <0.001 134.7557 113.75 -15.59% <0.001 99204 office/outpatient visit new patient (45-59 minutes) $158.33 169.93 7.33% <0.001 207.245 169.93 -18.01% <0.001 99205 office/outpatient visit new patient (60-74 minutes) $197.06 224.36 13.85% <0.001 257.9404 224.36 -13.02% <0.001 99211 office/outpatient visit established patient (5 minutes) $19.71 23.03 16.84% <0.001 25.79927 23.03 -10.73% 0.008 99212 office/outpatient visit established patient (10 minutes) $41.45 56.88 37.23% <0.001 54.2557 56.88 4.84% 0.123 99213 office/outpatient visit established patient (15 minutes) $68.97 92.47 34.07% <0.001 90.27781 92.47 2.43% 0.054 99214 office/outpatient visit established patient (30-39 minutes) $102.27 131.20 28.29% <0.001 133.8656 131.20 -1.99% 0.007 99215 office/outpatient visit established (40-54 minutes) $137.60 183.19 33.13% <0.001 180.1106 183.19 1.71% 0.044 *reimbursement rate for 99201 from 2021 unavailable. rate from 2020 was used as a proxy. supplemental table 1. comprehensive index of medicare reimbursement 2011 to 2021 no adjustment for inflation top 20 most common procedures hcpcs code description 2021 2020 2019 2018 2017 17003 destruction of premalignant lesion addon $ 6.63 $ 6.14 $ 5.77 $ 5.40 $ 5.74 17000 destruction of premalignant lesion $ 67.34 $ 66.77 $ 66.67 $ 67.68 $ 67.83 11102 tangential biopsy of skin $ 106.42 $ 102.49 $ 100.91 $ 108.00 $ 105.15 17110 destruction of benign lesion. $ 116.19 $ 114.40 $ 112.80 $ 114.48 $ 112.69 11103 tangential skin biopsy add-on $ 54.08 $ 54.50 $ 54.42 $ 33.48 $ 33.38 95044 allergy patch testing $ 5.58 $ 5.41 $ 5.77 $ 5.76 $ 5.74 17004 destruction of premalignant lesion addon $ 169.23 $ 161.68 $ 155.33 $ 147.96 $ 152.89 96910 photochemotherapy with uv-b $ 122.13 $ 118.37 $ 116.77 $ 115.56 $ 72.14 13132 complex repair (cheeks, chin, mouth, neck, axillae, genitalia, hands, feet) $ 491.30 $ 490.46 $ 492.29 $ 488.16 $ 485.57 17262 destruction of malignant lesion $ 182.49 $ 180.81 $ 180.56 $ 180.00 $ 178.01 11104 punch biopsy of skin lesion $ 133.29 $ 128.84 $ 126.86 $ 108.00 $ 105.15 12032 intermediate repair $ 316.13 $ 310.01 $ 311.74 $ 309.96 $ 309.00 11900 intralesional injection $ 57.57 $ 56.30 $ 55.50 $ 57.60 $ 56.70 77401 radiation treatment delivery $ 43.97 $ 24.90 $ 25.23 $ 25.56 $ 25.12 11602 excision of malignant lesion $ 253.67 $ 253.35 $ 254.44 $ 254.88 $ 253.02 13121 complex repair (scalp, arm, legs) $ 445.59 $ 441.74 $ 441.84 $ 437.76 $ 435.33 96900 ultraviolet light therapy $ 23.73 $ 22.74 $ 21.98 $ 21.24 $ 21.17 77280 set radiation therapy field $ 289.61 $ 283.30 $ 282.55 $ 287.28 $ 278.86 11301 shave skin lesion 0.6-1.0 cm $ 127.71 $ 124.51 $ 122.53 $ 123.12 $ 122.74 69100 biopsy of external ear $ 101.54 $ 100.69 $ 100.55 $ 103.32 $ 102.64 evaluation and management hcpcs code description 2021 2020 2019 2018 2017 99201 office/outpatient visit new patient (10 minutes) not available $ 46.56 $ 46.49 $ 45.36 $ 44.50 skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 126 99202 office/outpatient visit new patient (20 minutes) $ 73.97 $ 77.23 $ 77.48 $ 76.32 $ 75.72 99203 office/outpatient visit new patient (3044 minutes) $ 113.75 $ 109.35 $ 109.92 $ 109.80 $ 109.46 99204 office/outpatient visit new patient (4559 minutes) $ 169.93 $ 167.10 $ 166.86 $ 167.40 $ 166.17 99205 office/outpatient visit new patient (6074 minutes) $ 224.36 $ 211.12 $ 209.75 $ 210.60 $ 209.23 99211 office/outpatient visit established patient (5 minutes) $ 23.03 $ 23.46 $ 23.07 $ 21.96 $ 20.46 99212 office/outpatient visit established patient (10 minutes) $ 56.88 $ 46.20 $ 45.77 $ 44.64 $ 44.14 99213 office/outpatient visit established patient (15 minutes) $ 92.47 $ 76.15 $ 75.32 $ 74.16 $ 73.93 99214 office/outpatient visit established patient (30-39 minutes) $ 131.20 $ 110.43 $ 110.28 $ 109.44 $ 108.74 99215 office/outpatient visit established (4054 minutes) $ 183.19 $ 148.33 $ 147.76 $ 147.60 $ 146.43 top 20 most common procedures hcpcs code description 2016 2015b 2015a 2014 2013 17003 destruction of premalignant lesion add-on $ 5.73 $ 5.75 $ 5.72 $ 10.03 $ 6.81 17000 destruction of premalignant lesion $ 67.67 $ 67.20 $ 66.86 $ 75.23 $ 83.36 11102 tangential biopsy of skin $ 104.55 $ 104.93 $ 104.40 $ 102.45 $ 106.49 17110 destruction of benign lesion. $ 112.07 $ 112.11 $ 111.56 $ 109.26 $ 114.32 11103 tangential skin biopsy add-on $ 33.30 $ 33.06 $ 32.89 $ 32.60 $ 32.66 95044 allergy patch testing $ 5.73 $ 5.75 $ 5.72 $ 5.37 $ 5.78 17004 destruction of premalignant lesion add-on $ 152.89 $ 152.00 $ 151.24 $ 151.24 $ 172.84 96910 photochemotherapy with uv-b $ 72.14 $ 72.23 $ 71.87 $ 71.87 $ 76.21 13132 complex repair (cheeks, chin, mouth, neck, axillae, genitalia, hands, feet) $ 483.36 $ 483.31 $ 480.90 $ 475.37 $ 486.19 17262 destruction of malignant lesion $ 177.23 $ 177.15 $ 176.27 $ 173.74 $ 178.96 11104 punch biopsy of skin lesion $ 104.55 $ 104.93 $ 104.40 $ 102.45 $ 106.49 12032 intermediate repair $ 307.20 $ 306.87 $ 305.35 $ 301.27 $ 311.99 11900 intralesional injection $ 56.21 $ 56.06 $ 55.78 $ 55.17 $ 56.82 77401 radiation treatment delivery $ 24.35 $ 20.84 $ 20.74 $ 20.06 $ 20.75 11602 excision of malignant lesion $ 251.35 $ 250.82 $ 249.57 $ 247.18 $ 253.81 13121 complex repair (scalp, arm, legs) $ 433.23 $ 432.28 $ 430.13 $ 425.93 $ 437.20 96900 ultraviolet light therapy $ 20.77 $ 20.84 $ 20.74 $ 20.42 $ 22.12 77280 set radiation therapy field $ 276.05 $ 272.74 $ 271.38 $ 271.54 $ 181.00 11301 shave skin lesion 0.6-1.0 cm $ 121.02 $ 121.46 $ 120.85 $ 118.22 $ 123.16 69100 biopsy of external ear $ 102.04 $ 102.41 $ 101.90 $ 99.95 $ 103.77 evaluation and management hcpcs code description 2016 2015b 2015a 2014 2013 99201 office/outpatient visit new patient (10 minutes) $ 44.04 $ 44.20 $ 43.98 $ 43.35 $ 43.89 99202 office/outpatient visit new patient (20 minutes) $ 75.19 $ 75.46 $ 75.08 $ 74.51 $ 74.51 99203 office/outpatient visit new patient (30-44 minutes) $ 108.85 $ 109.60 $ 109.05 $ 108.19 $ 108.19 99204 office/outpatient visit new patient (45-59 minutes) $ 166.13 $ 166.73 $ 165.90 $ 166.22 $ 164.67 99205 office/outpatient visit new patient (60-74 minutes) $ 208.38 $ 209.49 $ 208.45 $ 207.06 $ 203.80 99211 office/outpatient visit established patient (5 minutes) $ 20.05 $ 20.12 $ 20.02 $ 20.06 $ 20.41 99212 office/outpatient visit established patient (10 minutes) $ 43.68 $ 44.20 $ 43.98 $ 43.70 $ 43.89 99213 office/outpatient visit established patient (15 minutes) $ 73.40 $ 73.30 $ 72.94 $ 73.08 $ 72.81 99214 office/outpatient visit established patient (30-39 minutes) $ 108.13 $ 108.88 $ 108.34 $ 107.83 $ 106.83 skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 127 99215 office/outpatient visit established (40-54 minutes) $ 145.72 $ 146.97 $ 146.24 $ 144.37 $ 142.90 top 20 most common procedures hcpcs code description 2012b 2012a 2011 17003 destruction of premalignant lesion add-on $ 7.15 $ 7.15 $ 7.14 17000 destruction of premalignant lesion $ 81.01 $ 81.01 $ 79.51 11102 tangential biopsy of skin $ 103.82 $ 103.82 $ 102.27 17110 destruction of benign lesion. $ 110.96 $ 110.96 $ 108.39 11103 tangential skin biopsy add-on $ 32.68 $ 32.68 $ 32.62 95044 allergy patch testing $ 6.13 $ 6.13 $ 6.12 17004 destruction of premalignant lesion add-on $ 171.89 $ 171.89 $ 171.92 96910 photochemotherapy with uv-b $ 72.16 $ 72.16 $ 69.31 13132 complex repair (cheeks, chin, mouth, neck, axillae, genitalia, hands, feet) $ 580.34 $ 580.34 $ 576.24 17262 destruction of malignant lesion $ 175.29 $ 175.29 $ 171.92 11104 punch biopsy of skin lesion $ 103.82 $ 103.82 $ 102.27 12032 intermediate repair $ 304.64 $ 304.64 $ 302.05 11900 intralesional injection $ 55.82 $ 55.82 $ 55.38 77401 radiation treatment delivery $ 22.12 $ 22.12 $ 25.48 11602 excision of malignant lesion $ 247.45 $ 247.45 $ 242.25 13121 complex repair (scalp, arm, legs) $ 443.85 $ 443.85 $ 438.64 96900 ultraviolet light therapy $ 21.44 $ 21.44 $ 20.73 77280 set radiation therapy field $ 187.55 $ 187.55 $ 188.91 11301 shave skin lesion 0.6-1.0 cm $ 93.26 $ 93.26 $ 91.74 69100 biopsy of external ear $ 102.79 $ 102.79 $ 102.95 evaluation and management hcpcs code description 2012b 2012a 2011 99201 office/outpatient visit new patient (10 minutes) $ 42.55 $ 42.55 $ 41.11 99202 office/outpatient visit new patient (20 minutes) $ 72.50 $ 72.50 $ 71.01 99203 office/outpatient visit new patient (30-44 minutes) $ 105.18 $ 105.18 $ 102.95 99204 office/outpatient visit new patient (45-59 minutes) $ 160.66 $ 160.66 $ 158.33 99205 office/outpatient visit new patient (60-74 minutes) $ 199.46 $ 199.46 $ 197.06 99211 office/outpatient visit established patient (5 minutes) $ 19.74 $ 19.74 $ 19.71 99212 office/outpatient visit established patient (10 minutes) $ 42.55 $ 42.55 $ 41.45 99213 office/outpatient visit established patient (15 minutes) $ 70.46 $ 70.46 $ 68.97 99214 office/outpatient visit established patient (30-39 minutes) $ 104.16 $ 104.16 $ 102.27 99215 office/outpatient visit established (40-54 minutes) $ 139.90 $ 139.90 $ 137.60 healthcare cpi top 20 most common procedures hcpcs code description 2021 2020 2019 2018 2017 17003 destruction of premalignant lesion addon $ 6.63 $ 6.20 $ 6.07 $ 5.84 $ 6.33 skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 128 17000 destruction of premalignant lesion $ 67.34 $ 67.42 $ 70.08 $ 73.15 $ 74.76 11102 tangential biopsy of skin $ 106.42 $ 103.49 $ 106.07 $ 116.74 $ 115.90 17110 destruction of benign lesion. $ 116.19 $ 115.51 $ 118.57 $ 123.74 $ 124.21 11103 tangential skin biopsy add-on $ 54.08 $ 55.03 $ 57.20 $ 36.19 $ 36.79 95044 allergy patch testing $ 5.58 $ 5.46 $ 6.07 $ 6.23 $ 6.33 17004 destruction of premalignant lesion addon $ 169.23 $ 163.25 $ 163.28 $ 159.93 $ 168.52 96910 photochemotherapy with uv-b $ 122.13 $ 119.52 $ 122.74 $ 124.91 $ 79.51 13132 complex repair (cheeks, chin, mouth, neck, axillae, genitalia, hands, feet) $ 491.30 $ 495.22 $ 517.48 $ 527.65 $ 535.21 17262 destruction of malignant lesion $ 182.49 $ 182.57 $ 189.80 $ 194.56 $ 196.21 11104 punch biopsy of skin lesion $ 133.29 $ 130.09 $ 133.35 $ 116.74 $ 115.90 12032 intermediate repair $ 316.13 $ 313.02 $ 327.69 $ 335.03 $ 340.59 11900 intralesional injection $ 57.57 $ 56.85 $ 58.34 $ 62.26 $ 62.50 77401 radiation treatment delivery $ 43.97 $ 25.14 $ 26.52 $ 27.63 $ 27.69 11602 excision of malignant lesion $ 253.67 $ 255.81 $ 267.46 $ 275.50 $ 278.89 13121 complex repair (scalp, arm, legs) $ 445.59 $ 446.03 $ 464.45 $ 473.17 $ 479.83 96900 ultraviolet light therapy $ 23.73 $ 22.96 $ 23.10 $ 22.96 $ 23.33 77280 set radiation therapy field $ 289.61 $ 286.05 $ 297.01 $ 310.52 $ 307.37 11301 shave skin lesion 0.6-1.0 cm $ 127.71 $ 125.72 $ 128.80 $ 133.08 $ 135.29 69100 biopsy of external ear $ 101.54 $ 101.67 $ 105.69 $ 111.68 $ 113.13 evaluation and management hcpcs code description 2021 2020 2019 2018 2017 99201 office/outpatient visit new patient (10 minutes) not available $ 47.01 $ 48.87 $ 49.03 $ 49.05 99202 office/outpatient visit new patient (20 minutes) $ 73.97 $ 77.98 $ 81.44 $ 82.49 $ 83.46 99203 office/outpatient visit new patient (30-44 minutes) $ 113.75 $ 110.41 $ 115.54 $ 118.68 $ 120.65 99204 office/outpatient visit new patient (45-59 minutes) $ 169.93 $ 168.72 $ 175.40 $ 180.94 $ 183.16 99205 office/outpatient visit new patient (60-74 minutes) $ 224.36 $ 213.17 $ 220.48 $ 227.64 $ 230.62 99211 office/outpatient visit established patient (5 minutes) $ 23.03 $ 23.69 $ 24.25 $ 23.74 $ 22.55 99212 office/outpatient visit established patient (10 minutes) $ 56.88 $ 46.65 $ 48.11 $ 48.25 $ 48.65 skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 129 99213 office/outpatient visit established patient (15 minutes) $ 92.47 $ 76.89 $ 79.17 $ 80.16 $ 81.49 99214 office/outpatient visit established patient (30-39 minutes) $ 131.20 $ 111.50 $ 115.92 $ 118.29 $ 119.86 99215 office/outpatient visit established (40-54 minutes) $ 183.19 $ 149.77 $ 155.32 $ 159.54 $ 161.40 top 20 most common procedures hcpcs code description 2016 2015b 2015a 2014 2013 17003 destruction of premalignant lesion addon $ 6.47 $ 6.74 $ 6.71 $ 12.07 $ 8.39 17000 destruction of premalignant lesion $ 76.46 $ 78.81 $ 78.41 $ 90.55 $ 102.73 11102 tangential biopsy of skin $ 118.13 $ 123.05 $ 122.43 $ 123.31 $ 131.23 17110 destruction of benign lesion. $ 126.63 $ 131.47 $ 130.83 $ 131.50 $ 140.88 11103 tangential skin biopsy add-on $ 37.63 $ 38.77 $ 38.57 $ 39.24 $ 40.25 95044 allergy patch testing $ 6.47 $ 6.74 $ 6.71 $ 6.46 $ 7.12 17004 destruction of premalignant lesion addon $ 172.75 $ 178.25 $ 177.36 $ 182.03 $ 213.00 96910 photochemotherapy with uv-b $ 81.51 $ 84.71 $ 84.28 $ 86.50 $ 93.92 13132 complex repair (cheeks, chin, mouth, neck, axillae, genitalia, hands, feet) $ 546.16 $ 566.79 $ 563.96 $ 572.15 $ 599.16 17262 destruction of malignant lesion $ 200.26 $ 207.75 $ 206.72 $ 209.11 $ 220.54 11104 punch biopsy of skin lesion $ 118.13 $ 123.05 $ 122.43 $ 123.31 $ 131.23 12032 intermediate repair $ 347.11 $ 359.87 $ 358.09 $ 362.61 $ 384.48 11900 intralesional injection $ 63.51 $ 65.74 $ 65.41 $ 66.40 $ 70.02 77401 radiation treatment delivery $ 27.51 $ 24.44 $ 24.32 $ 24.14 $ 25.57 11602 excision of malignant lesion $ 284.01 $ 294.14 $ 292.68 $ 297.50 $ 312.78 13121 complex repair (scalp, arm, legs) $ 489.51 $ 506.94 $ 504.42 $ 512.65 $ 538.78 96900 ultraviolet light therapy $ 23.47 $ 24.44 $ 24.32 $ 24.58 $ 27.26 77280 set radiation therapy field $ 311.91 $ 319.85 $ 318.25 $ 326.82 $ 223.06 11301 shave skin lesion 0.6-1.0 cm $ 136.74 $ 142.44 $ 141.72 $ 142.29 $ 151.78 69100 biopsy of external ear $ 115.30 $ 120.10 $ 119.50 $ 120.30 $ 127.88 evaluation and management hcpcs code description 2016 2015b 2015a 2014 2013 99201 office/outpatient visit new patient (10 minutes) $ 49.76 $ 51.83 $ 51.58 $ 52.18 $ 54.09 skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 130 99202 office/outpatient visit new patient (20 minutes) $ 84.96 $ 88.49 $ 88.05 $ 89.68 $ 91.82 99203 office/outpatient visit new patient (30-44 minutes) $ 122.99 $ 128.53 $ 127.89 $ 130.22 $ 133.33 99204 office/outpatient visit new patient (45-59 minutes) $ 187.71 $ 195.53 $ 194.55 $ 200.06 $ 202.93 99205 office/outpatient visit new patient (60-74 minutes) $ 235.45 $ 245.67 $ 244.45 $ 249.22 $ 251.15 99211 office/outpatient visit established patient (5 minutes) $ 22.65 $ 23.60 $ 23.48 $ 24.14 $ 25.15 99212 office/outpatient visit established patient (10 minutes) $ 49.35 $ 51.83 $ 51.58 $ 52.60 $ 54.09 99213 office/outpatient visit established patient (15 minutes) $ 82.94 $ 85.96 $ 85.54 $ 87.96 $ 89.73 99214 office/outpatient visit established patient (30-39 minutes) $ 122.18 $ 127.69 $ 127.05 $ 129.78 $ 131.65 99215 office/outpatient visit established (40-54 minutes) $ 164.65 $ 172.35 $ 171.50 $ 173.76 $ 176.10 top 20 most common procedures hcpcs code description 2012b 2012a 2011 17003 destruction of premalignant lesion addon $ 9.03 $ 9.03 $ 9.35 17000 destruction of premalignant lesion $ 102.29 $ 102.29 $ 104.07 11102 tangential biopsy of skin $ 131.09 $ 131.09 $ 133.87 17110 destruction of benign lesion. $ 140.11 $ 140.11 $ 141.88 11103 tangential skin biopsy add-on $ 41.26 $ 41.26 $ 42.70 95044 allergy patch testing $ 7.74 $ 7.74 $ 8.01 17004 destruction of premalignant lesion addon $ 217.04 $ 217.04 $ 225.03 96910 photochemotherapy with uv-b $ 91.11 $ 91.11 $ 90.72 13132 complex repair (cheeks, chin, mouth, neck, axillae, genitalia, hands, feet) $ 732.78 $ 732.78 $ 754.27 17262 destruction of malignant lesion $ 221.33 $ 221.33 $ 225.03 11104 punch biopsy of skin lesion $ 131.09 $ 131.09 $ 133.87 12032 intermediate repair $ 384.66 $ 384.66 $ 395.37 11900 intralesional injection $ 70.48 $ 70.48 $ 72.49 77401 radiation treatment delivery $ 27.93 $ 27.93 $ 33.35 11602 excision of malignant lesion $ 312.45 $ 312.45 $ 317.09 13121 complex repair (scalp, arm, legs) $ 560.44 $ 560.44 $ 574.15 96900 ultraviolet light therapy $ 27.07 $ 27.07 $ 27.13 skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 131 77280 set radiation therapy field $ 236.82 $ 236.82 $ 247.27 11301 shave skin lesion 0.6-1.0 cm $ 117.76 $ 117.76 $ 120.08 69100 biopsy of external ear $ 129.79 $ 129.79 $ 134.76 evaluation and management hcpcs code description 2012b 2012a 2011 99201 office/outpatient visit new patient (10 minutes) $ 53.73 $ 53.73 $ 53.81 99202 office/outpatient visit new patient (20 minutes) $ 91.54 $ 91.54 $ 92.95 99203 office/outpatient visit new patient (30-44 minutes) $ 132.81 $ 132.81 $ 134.76 99204 office/outpatient visit new patient (45-59 minutes) $ 202.86 $ 202.86 $ 207.24 99205 office/outpatient visit new patient (60-74 minutes) $ 251.85 $ 251.85 $ 257.94 99211 office/outpatient visit established patient (5 minutes) $ 24.93 $ 24.93 $ 25.80 99212 office/outpatient visit established patient (10 minutes) $ 53.73 $ 53.73 $ 54.26 99213 office/outpatient visit established patient (15 minutes) $ 88.97 $ 88.97 $ 90.28 99214 office/outpatient visit established patient (3039 minutes) $ 131.52 $ 131.52 $ 133.87 99215 office/outpatient visit established (40-54 minutes) $ 176.65 $ 176.65 $ 180.11 prior to 2019 all biopsy codes (red) were classified as 11100 for single lesion and 11101 for add-on conflict of interest disclosures: none funding: none corresponding author: kyle c. lauck, md 6431 fannin st suite jjl 315 houston tx, 77030 email: kyle.c.lauck@uth.tmc.edu references: 1. pollock jr, chen jy, dorius da et al. decreasing physician medicare reimbursement for dermatology services. j am acad dermatol. 2021 apr 24:s0190-9622(21)00897-5. doi: 10.1016/j.jaad.2021.04.059. epub ahead of print. pmid: 33901570. 2. haglin jm, eltorai aem, richter kr, jogerst k, daniels ah. medicare reimbursement for general surgery procedures: 2000 to 2018. ann surg. 2020 jan;271(1):17-22. doi: 10.1097/sla.0000000000003289. pmid: 30921048. 3. dominguez jl, ederaine sa, haglin jm, aragon sierra am, barrs dm, lott dg. medicare reimbursement trends for facility performed otolaryngology procedures: 2000-2019. laryngoscope. 2021 mar;131(3):496-501. doi: 10.1002/lary.28749. epub 2020 jul 3. pmid: 32619309. 4. gupta n, haglin jm, marostica cw, thornburg da, casey wj 3rd. trends in medicare reimbursement for reconstructive plastic surgery procedures: 2000 to 2019. plast reconstr surg. 2020 jul;146(1):1541-1551. 5. patel s, glasser d, repka mx, berkowitz s, sternberg p jr. changes in medicare reimbursement for commonly performed ophthalmic procedures. ophthalmology. 2021 mar 10:s0161-6420(21)00194-9. doi: 10.1016/j.ophtha.2021.02.026. epub ahead of print. pmid: 33713784. skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 807 research letter dermatological findings in children’s films fareen momin, bba1, vail reese, md2, richard f. wagner, jr, md1 1 department of dermatology, the university of texas medical branch at galveston, tx 2 union square dermatology, san francisco, ca children use media to learn attitudes and behaviors, developing morals based on media depictions.1 as their brains develop, children are able to decipher sounds and visual images presented in movies. symbolic dermatologic depictions are used by the film industry to help audiences distinguish between ‘good’ and ‘bad’ characters by portraying villains with recognizable skin findings. presenting villains with more skin findings than the heroes can serve to create prejudice.2 a 2011 study found that media’s portrayal of perfection causes psychological problems among females.3 castillo noted that disney presents its princesses in such a manner that is “impossible … for humans to achieve” like princess aurora from sleeping beauty.4 having children idolize characters that are not visually and physically attainable can negatively impact the mental health of children as they age. a 2017 study that analyzed villains from classic movies found that dermatologic findings in villains included alopecia, periorbital hyperpigmentation, androgenic alopecia, deep rhytids, scars, verucca vulgaris, and rhinophyma.3 a subsequent study analyzed animated films for the use of dermatological findings and found significantly more skin findings in antagonists compared to protagonists. balding, periorbital darkness, and moles were abstract introduction: filmmakers use dermatologic findings to help the audiences decipher between ‘good’ and ‘bad’ characters by portraying villains with recognizable skin findings. the objective of this study was to analyze 18 disney live-action movies in relation to their earlier animated releases to determine whether there were changes or correlation about how the industry portrayed certain characters based on their roles as heroes or villains. methods: to better understand how the use of dermatological findings are changing in the film industry, eighteen disney live-action movies in relation to their earlier animated releases were compared for changes or correlation on how the industry portrays certain characters based on their roles as heroes or villains. results: film antagonists were depicted with significantly more dermatologic findings than protagonists (p<0.0001). in addition, the frequency of periorbital hyperpigmentation (p=0.02) and nasolabial folds (p=0.05) were significantly higher in antagonists versus protagonists. discussion: these findings have important implications about the dermatological content of movies directed toward children. findings of this study suggest filmmakers are continuing to use common dermatological findings to indirectly portray characters as ‘good’ or ‘bad.’ skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 808 table 1. dermatological findings by character type and film type. dermatological findings hero villain pvalue* original film remake film pvalue* characters from original film characters from remake film rhytides 3 6 0.25 5 4 1.00 lady tremaine, queen of hearts, cruella de vil, prince adam (human form), shan yu gaston, prince adam (human form), prince adam (beast form), bori khan nasolabial folds 2 7 0.05 3 6 0.44 lady tremaine, queen of hearts, jafar lady tremaine, cruella de vil, prince adam (beast form), jafar, aladdin, bori khan periorbital puffiness 0 2 0.31 1 1 1.00 lady tremaine gaston periorbital hyperpigmentation 0 5 0.02 2 3 1.00 cruella de vil, jafar maleficent, cruella de vil, jafar poliosis 0 3 0.09 2 1 1.00 lady tremaine, cruella de vil cruella de vil scar 2 1 1.00 0 3 0.23 none mowgli, prince adam (beast form), bori khan gray-hued skin 0 3 0.09 3 0 0.23 maleficent, cruella de vil, shan yu none alopecia 0 3 0.09 2 1 1.00 ringmaster, shan yu red queen hypopigmented skin 0 2 0.21 0 2 0.48 none red queen, maleficent hyperpigmented beauty mark 0 1 0.47 0 1 1.00 none red queen buccula 0 1 0.47 1 0 1.00 queen of hearts none total 7 34 0.0001 19 22 0.71 not applicable not applicable *fisher’s exact test was used to determine statistical significance between dermatological findings and film type. ttest was used to compare mean total number of dermatological findings and film type. chi-square tests and fisher’s exact tests were used to determine associations between dermatological findings and character type. all analyses and data management were performed using sas statistical software, version 9.4 (sas institute inc., cary, nc). skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 809 table 2. dermatological findings by movie release and character type. number of protagonists in original movies 9 number of protagonists in remake movies 9 number of antagonists in original movies 8 number of antagonists in remake movies 8 total number of dermatological findings in protagonists 7 total number of dermatological findings in antagonists 34 number of dermatological findings in protagonists of original film 1 number of dermatological findings in protagonists of remake film 6 number of dermatological findings in antagonists of original film 18 number of dermatological findings in antagonists of remake film 16 mean (std) of dermatological findings in of protagonists in original film 0.11 ± 0.33* mean (std) of dermatological findings in of protagonists in remake film 0.67 ± 1.09* p-value comparing dermatological findings in protagonists in original verses remake films 0.146* mean (std) of dermatological findings in of antagonists in original film 2.25 ± 1.49* mean (std) of dermatological findings in of antagonists in remake film 2.00 ± 1.07* p-value comparing dermatological findings in antagonists in original verses remake films 0.705* *t-test was used to determine whether there was a difference in the number of dermatological findings in protagonist of original and remake films. in addition, t-test was also used to determine whether there was a difference in the number of dermatological findings in antagonists of original and remake films. all analyses and data management were performed using sas statistical software, version 9.4 (sas institute inc., cary, nc). depicted on antagonists at a significantly higher frequency than protagonists.5 the objective of this study was to analyze 18 disney live-action movies in relation to their earlier animated releases to determine whether there were changes or correlation about how the industry portrays certain characters based on their roles as heroes or villains. live-action productions of animated films involve actors instead of animated portrayals. movies analyzed were dumbo (1941), dumbo (2019), cinderella (1950), cinderella (2015), alice in wonderland (1951), alice in wonderland (2010), sleeping beauty (1959), maleficent (2014), 101 skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 810 dalmatians (1961), 102 dalmatians (2000), the jungle book (1967), the jungle book (2016), beauty and the beast (1991), beauty and the beast (2017), aladdin (1992), aladdin (2019), mulan (1998), and mulan (2020). the total number of dermatological findings found based on the 18 movies analyzed was 41, of which 7 were identified in protagonists and 34 in antagonists (table 1, p<0.0001). antagonists exhibited higher percentages of all skin findings except for scars. periorbital hyperpigmentation (p=0.02) and nasolabial folds (p=0.05) were significantly higher in antagonists. no statistical differences were found between the original and remake films for dermatologic depictions by time of release. however, dermatological findings and character classification were remarkable for an increase for protagonists in the remake films compared to original film versions (table 2, 1 vs. 6). an important methodological limitation of this study relates to classifying skin findings in characters. subjectivity is possible when identifying dermatological findings in characters, especially in animated films where at times it is difficult to decipher artist intentions with certainty. to limit and reduce subjectivity, all authors confirmed the findings presented. this analysis of children’s movies indicates that villain depictions include incorporation of skin disease representations that are often absent in heroes. because many movie villains present with common skin findings, children with similarities may begin to identify with antagonists simply based on film depictions. dermatological depictions may also stigmatize large groups based on appearance that will inevitably affect many individuals in our communities. comparing the use of skin depictions in original and remake films suggests that filmmakers continue to use common dermatological findings to portray characters as villains, thereby teaching young viewers that dermatological conditions define the moral character of an individual. conflict of interest disclosures: none funding: none corresponding author: fareen momin, bba 4407 pine blossom trail houston, tx 77059 email: faamomin@utmb.edu references: 1. villani s. impact of media on children and adolescents: a 10-year review of the research. j am acad child adolesc psychiatry. 2001;40(4):392–401. doi:/10.1097/00004583200104000-00007 2. croley ja, reese v, wagner rf jr. dermatologic features of classic movie villains: the face of evil. jama dermatol. 2017;153(6):559–564. doi:10.1001/jamadermatol.2016.5979 3. magin p, adams j, heading g, pond d. 'perfect skin', the media and patients with skin disease: a qualitative study of patients with acne, psoriasis and atopic eczema. aust j prim health. 2011;17(2):181–185. doi:/10.1071/py10047. 4. castillo, p. (2006, december 4). the negative effects of disney on children, from https://sundial.csun.edu/9674/archive/thenegative effectsofdisneyonchildren/, december 4, 2006. accessed january 31, 2021. 5. ryan mp, reese v, wagner rf jr. dermatological depictions in animated movies. br j dermatol. 2018;179(4):982– 983.doi:org/10.1111/bjd.16880 https://sundial.csun.edu/9674/archive/thenegativeeffectsofdisneyonchildren/ https://sundial.csun.edu/9674/archive/thenegativeeffectsofdisneyonchildren/ prevalence of anxiety, depression, and attention deficit disorder in patients with primary hyperhidrosis • primary hyperhidrosis is a chronic and socially disabling disorder with a significant impact on quality of life. • it has an estimated us prevalence of 4.8% (~15.3 million people).1 • few studies have attempted to estimate the prevalence of mental illness in patients with hyperhidrosis, and the results have been conflicting.2-5 • estimate the prevalence of depression, anxiety and attention deficit disorder (add) in patient was primary hyperhidrosis. • understand the correlation between hyperhidrosis location and severity with mental health • 500 patients included • 13.8% of patients had a diagnosis of anxiety, 12.4% had depression and 6.4% had add • positive correlations between the number of anatomical hh sites involved and the prevalence of psychiatric conditions • no association with overall hdss severity or location involved with prevalence of psychiatric conditions. • there is a significant association between hh and the prevalence of anxiety, depression and add regardless of gender or age • compared to the nationally reported prevalence of anxiety (5.7%)6, depression (7.8%)7 and add (4.4%) 8, hh patients have a statistically significant higher prevalence than the general public. • our study found the prevalence of anxiety 13.8%, depression 12.4% and add 6.4% • the severity and/or location of hh do not correlate with prevalence of anxiety, depression and add. • however, there is a positive correlation between the number of anatomical sites involved and the prevalence of these comorbidities. • providers should be aware of the increased prevalence of mental health disorders in patients with hyperhidrosis. • an irb approved retrospective review: • patients diagnosed with primary hyperhidrosis from 2011-2018 at a single site were identified at time of initial evaluation. • age of onset, age at time of initial evaluation, gender, hyperhidrosis locations and disease severity using hyperhidrosis disease severity scale (hdss) were recorded • hdss was used as a maker of location severity. • patients were considered to have anxiety, depression, and/or add diagnosis if: (1 or more) • self reported diagnosis on intake form • had an icd9 code of diagnosis clinical note documenting diagnosis • taking add specific medication 1. doolittle et al. arch dermatol res. 2016;308(10):743-9. 2. bahar r, liu y, huang y, et al. the prevalence of anxiety and depression in patients with or without hyperhidrosis (hh). j am acad dermatol. 2016;75:1126-1133 3. braganca gm, lima so, pinto neto af, marques lm, melo ev, reis fp. evaluation of anxiety and depression prevalence in patients with primary severe hyperhidrosis. an bras dermatol. 2014;89:230-235. 4. weber a, heger s, sinkgraven r, heckmann m, elsner p, rzany b. psychosocial aspects of patients with focal hyperhidrosis. marked reduction of social phobia, anxiety and depression and increased quality of life after treatment with botulinum toxin a. br j dermatol. 2005;152:342-345 5. klein sz, hull m, gillard kk, peterson-brandt j. dermatology and therapy, 2020;10:12991314 6. harvard medical school national comorbidity survey (ncs). 2017 7. national survey on drug use and health (nsduh) 2019 8. kessler rc, adler l, barkley r, biederman j, conners ck, demler o, faraone sv, greenhill ll, howes mj, secnik k, spencer t, ustun tb, walters ee, zaslavsky am. the prevalence and correlates of adult adhd in the united states: results from the national comorbidity survey replication. am j psychiatry. 2006 apr;163(4):716-23. methods objective results conclusion: ella glaser md1, king rosemary pa-c2, dee anna glaser md2 1university of miami dr. phillip frost department of dermatology and cutaneous surgery 2saint louis university department of dermatology references: synopsis psychiatric diagnosis prevalence (%) anxiety 13.8 depression 12.4 attention deficit disorder (add) 6.4 characteristic value total number of patients 500 age: mean age of onset 15 mean age at time of evaluation 30 sex number (%) female 356 (71.2) male 144 (28.8) number of sites involved 1 to 3 307 (61.4) 4 to 6 124 (24.8) 7 to 9 69 (13.8) dr. dee anna glaser is a consultant for dermira, inc., and an investigator for allergan, atacama therapeutics, brickell biotech, inc., galderma, and revance therapeutics, inc. she has received honoraria for consulting with allergan and dermira, inc. disclosures skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 174 short communication subacute cutaneous lupus erythematosus associated with ramucirumab therapy elise hogan, bs1, kelsey nusbaum, bs1, anne householder, md1 1university of cincinnati college of medicine, cincinnati, oh lupus erythematosus is an autoimmune inflammatory condition with a constellation of clinical findings including fever, malaise, myalgias, and loss of appetite/weight.1 subsets of this disease are numerous, with subacute cutaneous lupus erythematosus (scle) demonstrating cutaneous manifestations. while the etiology of scle is often multifactorial, drugs can induce scle in up to 30% of cases. drug-induced scle was first documented in 1985 in association with hydrochlorothiazide, and has since been described in association with numerous medications.2 hydralazine, procainamide, isoniazid are the three highest risk medications for lupus erythematosus, while scle associated medications are primarily hydrochlorothiazide, calcium channel blockers, and ace inhibitors.3 there has been increasing discussion surrounding chemotherapeutic agents inducing scle, with highest risk medications of docetaxel, paclitaxel, fluorouracil, capecitabine, tamoxifen citrate, and doxorubicin.3 ramucirumab is a fully human monoclonal antibody that targets vegfr2, indicated in patients with hepatocellular carcinoma with prior treatment of sorafenib. common side effects include thrombocytopenia, hypoalbuminemia, hyponatremia, neutropenia, fatigue, edema, and hypertension.4 there have been no known associations between ramucirumab and scle. a 64-year-old male with a history of hepatitis c, hepatocellular carcinoma, and cirrhosis recently started on ramucirumab presented to clinic with a three-month history of worsening pruritic eruption. the patient received three cycles of ramucirumab. his medications included insulin glargine and lispro, levothyroxine, losartan, nadolol, prochlorperazine, and sildenafil, all stable prior to beginning ramucirumab. the patient had received nivolumab infusions with a resolved dermatitis and sorafenib earlier in disease progression that was discontinued for fatigue. physical exam revealed an annular erythematous eruption with scaling patches on bilateral upper extremities in a photosensitive distribution clearly demarcated by clothing lines (figure 1), clinically suspicious for scle. the differential included systemic lupus erythematosus (sle), dermatomyositis, nummular atopic dermatitis, and lichen planus. the skin biopsy revealed skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 175 figure 1. clinical photo of presenting rash parakeratosis with loss of the granular layer, dyskeratosis, disorganized and crowded basal layer solar elastosis and a moderate perivascular lymphocytic infiltrate in the papillary and available superficial reticular dermis (figure 2). the anti-nuclear antibody (ana) panel was significant for anti-ssa (ro) antibodies greater than 8.0 ai (standard range 0-0.9ai). figure 2. histopathologic section of patient specimen, showing cytotoxic dermatitis. h&e stained at 20x magnification. the biopsy findings are highly consistent with cytotoxic dermatitis. this, in combination with the presence of anti-ssa antibodies, supported clinical suspicions of scle. anti-ro antibodies are present in 80% of patients with proven scle.5 conditions such as dermatomyositis and sle are less likely due absence of systemic symptoms. the authors are not aware of other reports of scle due to ramucirumab monotherapy. there have been reports of other vegf biologic therapies that developed scle, such as bevacizumab and ranibizumab.6 however, these medications are humanized antibodies against vegf-a. there were no other confounding medications on his list. cases of nivolumab causing a scle eruption have been reported; however, was associated with concurrent use and not after discontinuation. there is the potential that previous nivolumab therapy could have contributed to this eruption; however, the only significant medication change in the past year was ramucirumab which likely caused the exanthem. in conclusion, ramucirumab can be associated with subacute cutaneous lupus erythematosus. conflict of interest disclosures: none funding: none corresponding author: elise hogan, bs 231 albert sabin way cincinnati, oh 45229 email: hoganes@mail.uc.edu references: 1. cojocaru, m., cojocaru, i. m., silosi, i., & vrabie, c. d. manifestations of systemic lupus erythematosus. maedica, (2011), 6(4), 330–336. [pmid: 22879850] 2. reed br, huff jc, jones sk, et al. subacute cutaneous lupus erythematosus associated with hydrochlorothiazide therapy. ann intern med. 1985 jul;103(1):49-51. [pmid: 3873891]. 3. bolton c, chen y, hawthorne r, et al. systematic review: monoclonal antibodyinduced subacute cutaneous lupus erythematosus. drugs r d. 2020 dec;20(4):319-330. [pmid: 32960413]. 4. zhu ax, kang yk, yen cj, et al. reach-2 study investigators. ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increased αfetoprotein concentrations (reach-2): a mailto:hoganes@mail.uc.edu mailto:hoganes@mail.uc.edu skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 176 randomised, double-blind, placebocontrolled, phase 3 trial. lancet oncol. 2019 feb;20(2):282-296. [pmid: 30665869]. 5. cleaver n, ramirez j, gildenberg s. cutaneous lupus erythematosus in a patient undergoing intravitreal bevacizumab injections: case report and review of the literature. j drugs dermatol. 2013 sep;12(9):1052-5. [pmid: 24002156]. 6. andric m, dixit s, robaei d, watchorn r, verma n. a case of subacute cutaneous lupus erythematosus as a result of ranibizumab (lucentis) treatment. indian j ophthalmol. 2013 dec;61(12):752-4. [pmid: 24212210]. skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 398 brief article multiple sebaceous carcinomas in an african american patient with muir-torre syndrome jason patel, bs1, callie hill, md2, bonnie hodge, md2, carlton b. phillips, md2 1 heersink school of medicine, university of alabama at birmingham, birmingham, al 2 department of dermatology, university of alabama at birmingham, birmingham, al muir-torre syndrome (mts), a variant of hereditary nonpolyposis colorectal cancer (hnpcc) or lynch syndrome, is a rare autosomal dominant condition that is seen in adult patients. it is characterized by visceral malignancies and skin tumors, most notably sebaceous neoplasms. although sebaceous neoplasms are typically slow growing and benign, sebaceous carcinomas can be aggressive and warrant early intervention.1 there are no reports in the literature describing sebaceous carcinoma in african american patients with mts. we present a 40-year-old african american patient with multiple sebaceous carcinomas in the setting of mts. a 40-year-old african american male presented to dermatology clinic with two nontender non-draining “cysts” on the back. the patient reports these lesions appeared and grew rapidly over the previous 1-2 months. past medical history was notable for end-stage renal disease and hidradenitis suppurativa. physical exam (figure 1a – 1c) revealed lesion a, a soft fleshy hyperpigmented papule on the left back with heme crusting and erythema and lesion b, a large 3 x 4 cm broad-based hyperpigmented and pink pedunculated plaque with comedones on the left back. a shave biopsy was performed on lesion a and excisional biopsy was performed for lesion b. initial differential diagnosis included inflamed intradermal nevus, inflamed seborrheic keratosis, cyst, or hidradenitis suppurativa in the setting of history of axillary hurley stage ii disease. histopathology of lesions a and b revealed sebaceous carcinoma. upon further discussion, the patient mentioned a history of colon cancer, diagnosed at 34 years old. family history was notable for colon and pancreatic cancer in his mother who carried a diagnosis of lynch syndrome. family history further revealed history of pancreatic cancer in the maternal grandmother. the patient’s mayo muir-torre syndrome risk score was equal to 3, suggesting an increased likelihood of mts.2 immunohistochemical stains for mismatch repair gene expression revealed tumor cells positive for mlh1, pms2, and msh6 and negative for msh2 indicating microsatellite instability. the patient underwent mohs micrographic surgery (mms) to treat the sebaceous carcinomas on the left back, with both requiring one stage for clearance. at the time of surgery, an additional suspicious skin-colored nodule introduction case report skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 399 was noted in the groin, lesion c (not pictured). a scout biopsy was performed with histopathology revealing sebaceous carcinoma. the patient subsequently underwent mms with one stage required for clear margins. figure 1a. left back showing lesions a and b, histologically confirmed to be sebaceous carcinomas figure 1b. lesion a left mid back. a soft fleshy hyperpigmented papule on the left back with heme crusting and erythema. figure 1c. lesion b left inferior back. a broadbased hyperpigmented and pink pedunculated plaque with comedones. mismatch repair gene expression skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 400 mlh1: expressed in tumor cells (positive) pms2: expressed in tumor cells (positive) msh2: not expressed in tumor cells (negative) msh6: expressed in tumor cells (positive) to our knowledge, there are currently only 3 cases of sebaceous neoplasms in african american patients described in the literature.3,4,5 of these, one case report details an african american patient with a diagnosis of mts and a biopsy-proved sebaceous adenoma of the back.3 moon et al. reported one patient with a pruritic, erythematous, mildly lichenified plaque on the abdomen with biopsy revealing sebaceous carcinoma; this patient did not have an associated mts.4 another author theorized the occurrence of sebaceous neoplasms in african americans without mts and a potential relationship between the immunosuppressive state in end-stage renal failure.5,6 as noted in this patient, concomitant hidradenitis suppurativa disease could delay diagnosis if sebaceous neoplasms present within typical areas of hs disease (axilla, groin, buttocks, inframammary chest) or with similar clinical features, particularly follicular occlusion lesions.7 clinicians should obtain a careful medical and family history when cyst-like lesions present with unusual features or in patients with known mts. it is also important to consider differences in clinical appearance of sebaceous neoplasms in skin of color. dermatologists should have a low threshold to sample suspicious lesions or refer for excisional biopsy if not amenable to simple shave removal. specific staining patterns of mlh1, pms2, and msh6 positivity and msh2 negativity are helpful to identify tumors with microsatellite instability and patients with risk of msh2 germline mutation necessitating further work-up. in patients with diagnosed sebaceous neoplasms, the mayo muir-torre syndrome risk score should be calculated.2 for scores of 2 or greater, patients may have an increased likelihood of mts and referral to appropriate subspecialities is pertinent. conflict of interest disclosures: none funding: none corresponding author: jason patel 9167 brenham ct montgomery, al 36117 phone: 334-655-1418 email: jason96@uab.edu references: 1. john am, schwartz ra. muir-torre syndrome (mts): an update and approach to diagnosis and management. j am acad dermatol. 2016;74(3):558-566. pmid: 26892655 2. roberts me, riegert-johnson dl, thomas bc, et al. a clinical scoring system to identify patients with sebaceous neoplasms at risk for the muirtorre variant of lynch syndrome. genet med. 2014;16(9):711-716. pmid: pmid: 24603434 3. wargo jj, plaza ja, carr d. sebaceous neoplasia leading to the diagnosis of muir-torre syndrome in an african american man. jaad case rep. 2021;11:72-73. published 2021 mar 23. pmid: 33937470 4. moon tc, cassler nm, lackey jn. sebaceous carcinoma on the abdomen in an africanamerican male patient. indian dermatol online j. 2015;6(suppl 1):s27-s29. pmid: 26904445 5. kaminska ec, iyengar v, tsoukas m, shea cr. borderline sebaceous neoplasm in a renal transplant patient without muir-torre syndrome. j cutan pathol. 2013;40(3):336-340. pmid: 23174034 6. descamps-latscha b. the immune system in end-stage renal disease. curr opin nephrol hypertens. 1993;2(6):883-891. pmid: 7922228 7. sabat r, jemec gbe, matusiak ł, kimball ab, prens e, wolk k. hidradenitis suppurativa. nat rev dis primers. 2020;6(1):18. published 2020 mar 12. pmid: 32165620 discussion 72 1 figure 3. improvement in the skin texture: decrease in the texture count (s)=p<0.001. -7% (s) 4. 45 4. 15 efficacy on firming and contouring effects face volumefacescan® visia® (photographs analysis) dynaskin® dermatop® cutometer® subjective efficacy and organoleptic properties questionnaires: statistical analysis was performed to determine the variations obtained under the effect of the cc by a paired samples t-test. 3d analysis software skin firmness skin biomechanical properties an open label, prospective, clinical study to evaluate the antiaging effects and the safety of a novel cosmetic facial day cream. fall clinical dermatology conference® october 12-15, 2017. las vegas, nevada, usa granger c., martinez-masana g., garre a. innovation and development isdin barcelona spain introduction skin aging is a complex biological process influenced by a combination of intrinsic and extrinsic factors determining both photo and chronological aging. the aim of this study was to evaluate both objective and subjective efficacy measurements at d28 and d56 of the new cosmetic cream (cc) containing carnosine, palmitoyl oligopeptide, palmitoyl tetrapeptide-7, an innovative alteromonas ferment extract (afe) and hyaluronic acid (ha). the tolerance of the cc was recorded along the study.  methods results at d56, there was a significant decrease of the ptosis volume (figure 1 and 2). this effect was measured in 82% of the subjects. at d56 the surface of the skin was smoother (p=0.028) (figure 3) and a reduction of the skin deformation (p<0.001) was observed which confirmed the firming effect of the product (figures 4 and 5). at d28 and d56 skin elasticity significantly improved in 54% (p=0.008) and 83% (p<0.001) of the subjects, respectively (figure 6). assessment of skin complexion on visia® at d56 showed a reduction of 6% (p=0.010) of spots (brown or red skin lesions, including freckles, hyperpigmentation and vascular lesions) which contributed of improvement of skin even (figure 7). subjects reported their satisfaction on perceived efficacy and organoleptic properties of the products (figure 8). conclusions the data demonstrated that the novel cosmetic facial cream has significant anti-aging effects. after 56 days of use, there were demonstrated improvements of skin firmness, moisturization, and elasticity. these improvements contributed to the overall refining effect on the facial contour and an improvement of skin complexion. the safety and tolerance of the product were good. no adverse event was reported. referencias: a.garre, g.martinez-masana, j.piquero-casals, c.granger. redefining face contour with a novel anti-aging cosmetic product: an open-label, prospective clinical study. dove med press [accepted]. dobrev h. use of cutometer to assess epidermal hydration. skin res technol. 2000 nov;6(4):239-244. isdin s.a.provencals, 33 barcelona spain fi g u re 3 100 80 60 40 20 0 120 0 -29% (s) open, intra-individual study n=33 45 65 y. d0 d28 cc twice a day d56 figure 1. remodeling effect: decrease in the average volume of the ptosis (s)=p<0.001 fi g u re 1 3.90 4.00 4.10 4.40 4.30 4.50 d0 d0 d56 facescan® image d56 4.20 v o lu m e (i n m l) figure 6. elasticity: increase in the r2 (total recovery of the initial state/final defromation) parameter (s)=p<0.001 fi g u re 6 r 2 va lu e (i n m m ) figure 2. 7% decrease of ptosis volume after 56 days of use the blue zone characterizes a decrease in the cheek volume so a decrease in ptosis te xt u re c o u n t d0 d28 d56 d0 d28 d56 -12% (s) -10% (s) 80 3 70 8 fi g u re 4 v o lu m e (i n m m 3 ) 0. 57 9 figure 4 and 5. firming effect: decrease in the average volume of the skin deformation (s)=p<0.001. fi g u re 5 d ep th ( in m m ) d0 d28 d56 -29% (s) -34% (s)0 .8 79 0. 61 6 72 1 80 3 70 8 -34% (s) 0.8 0.6 0.4 0.2 0.0 1.0 0.50 0.52 0.54 0.58 0.62 0.56 0.66 0.64 0.68 0.60 d0 d28 d56 60 62 64 61 66 65 67 63 decrerase in the red spot d0 d28 -6% (s) 67 63 figure 7. less red skin after 56 days. significant decrease in the red spot, (s)=p<0.001 fi g u re 7 r ed . s p o t figure 8. product efficacy by self-evaluation questionnaire. fi g u re 8 0. 65 4 +20% (s) +17% (s) 0. 56 0 0. 67 3 recovers elasticity and density product efficacy by self-evaluation questionnaire firmer visibility retightened more moisturized satisfied subjects (%). d56 0 80604020 100 660 680 720 700 800 780 820 740 760 fc17posterisdincosmeticdaycreamgranger.pdf a case study series to evaluate the safety and efficacy of a novel keratolytic in patients diagnosed with plaque psoriasis tien q. nguyen, m.d., andrea nguyen, ms, pa-c first o c dermatology, fountain valley, ca background many patients with plaque psoriasis suffer from noticeable physical disease aff liction. globally, the prevalence of psoriasis reported in populationbased studies in adults ranges from 1% to 8.5%, with differences based on geographic location.1 treatment can be burdensome and includes keratolytics for scale and plaques reduction. a new treatment for plaque psoriasis, which aids in the gentle physical removal of the scale has been developed with the purpose of removing scale without causing irritation, spot bleeding and infection. loyon® (pb/lo-112) is a unique, patented combination of the dry emollient cetiol® cc and the medical silicone oil dimethicone. the combination of the 2 substances gives loyon® a low surface tension as well as high creep and spreading properties. the liquid is very easily applied and allows a gentle yet effective lifting of scales. this study evaluated the safety and effectiveness of loyon® in treating plaque and scaling buildup in patients diagnosed with plaque psoriasis. results all 8 patients completed the study and showed improvement of their scaling with a 43% overall reduction. overall, pasi scores improved by 19% upon completion of treatment. there were no adverse events reported and most of the patients stated that they were satisfied with the performance of the study medication on their plaque psoriasis. conclusions loyon® improved scaling in patients with plaque psoriasis and had a favorable safety profile. additionally, patients were pleased with the performance of this novel keratolytic. reference objectives methods eight patients were enrolled in this open label study. each had a diagnosis of plaque psoriasis with scaling. there were 2 study visits—visit 1 (baseline) and visit 2 (end of study visit). during the study period, patients were asked to refrain from using any other products to treat their plaque psoriasis. pictures of a designated target area of the subjects’ plaque psoriasis were taken at each visit. at each visit the study investigator rated the patient’s psoriasis area severity index and overall investigator’s global assessment. evaluation of treatment results ranged from live assessment (by the investigator) to photographic assessment. patients received loyon® study medication at visit 1 and were instructed how to apply loyon® onto dry skin and gently massage it into the skin. patients were asked to leave medication on the skin for at least 3 hours before washing it off with a mild cleanser and/or shampoo. patients applied medication twice a day for 7 consecutive days, and up to an additional 7 consecutive days if needed for patients with more severe scales. patient with plaque psoriasis on the elbow at visit 1 (a) and visit 2 (b) a b patient with plaque psoriasis on the forehead at visit 1 (a) and visit 2 (b) a b patient with plaque psoriasis of the hand at visit 1 (a) and visit 2 (b) 1. michalek im, loring b, john sm. a systematic review of worldwide epidemiology of psoriasis j eur acad dermatol venereol. 2017;31(2):205. a b patients completed a diary capturing their application compliance. additionally, they were asked to complete a one-page survey to determine their evaluation and compliance of the study medication. fc17posterintradermnguyenacasestudyseries.pdf skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 533 covid concepts telogen effluvium in patients recovering from covid-19 nancy wei, ms1, emily elbogen, pa-c1, joshua dan, ms1, anna chessky, bs1, ryan riveraoyola, ms1, mark lebwohl, md1 1the kimberly and eric j. waldman department of dermatology, icahn school of medicine at mount sinai hospital, new york, ny telogen effluvium (te) is a non-scarring alopecia characterized by diffuse hair shedding that has recently been reported as a post-infectious manifestation of the novel coronavirus sars-cov-2.1 in response to physiological or psychological stress, premature termination of the anagen phase and subsequent transition to the telogen phase of hair growth result in shedding of hair follicles 2-3 months after the precipitating event. the condition is usually self-limited, with acute cases resolving within 6 months of onset.2 it has been proposed that proinflammatory cytokines, impaired anti-coagulation and severe psychosocial stress of covid-19 triggers te in survivors recovering from the disease.3 we describe ten cases of a telogen effluvium following covid-19 infection from an ambulatory dermatology clinic in new york city, an early epicenter of the pandemic and review the current literature. abstract background: we characterized and summarized clinical and demographic features in patients with post-covid 19 telogen effluvium and compared it with those reported in the literature. methods: we collected data from 10 participants and measured average onset of te from initial covid-19 symptoms, medical intervention for covid-19 infection, physical exam findings, and whether or not patient experienced resolution of te symptoms after 14 weeks. we performed a literature review using the terms “telogen effluvium”, “covid” and “hair” and investigation was limited to adult case reports and cohort studies appearing in the english-language literature as of march 2021. clinical and demographic findings were analyzed and compared with those of our patient cohort. results: nine out of ten patients in our cohort had mild covid-19 symptoms only with mean onset of hair shedding was 73 days following infection. none had previous history of hair loss. by contrast, of the 28 patients identified in the literature review 50% of these patients were hospitalized for severe covid-19 infection with average onset of te 87 day after infection. 12% of these patients had preexisting androgenic alopecia. conclusion: telogen effluvium is a distressing, yet self-limited condition that can occur following both mild and severe covid-19 infection. dermatologists should expect an increase in te in areas heavily affected by covid-19 and reassure patients of the likely cause and that symptoms will resolve over time. introduction https://paperpile.com/c/oo8g4l/utvm skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 534 for the literature review portion , a pubmed search was conducted with the following terms, “telogen effluvium”, “covid” and “hair” without any boolean operators and investigation was limited to adult case reports and cohort studies appearing in the english-language literature as of march 2021. articles wherein the full text was not available or of an irrelevant publication type such as literature reviews, conference abstracts, posters, and editorials were excluded. out of the eleven results, three did not match the publication type and three were not descriptive case reports. in total, five publications with reported cases of post covid-19 te were included in the study. we report 10 patients who developed acute, new onset te weeks after covid-19 infection. patient demographics and clinical features are summarized in table 1. the patients ranged from 20 to 68 years old with a median age of 56 years and were 60% female. all patients had pcr or antibody confirmed covid-19 infection and denied previous history of hair loss. no new medical conditions, medications, or lifestyle modifications aside from covid-19 were reported. only one patient was hospitalized for a severe covid-19 infection that lasted 40 days and required 21 days of mechanical ventilation. the other nine patients exhibited mild symptoms limited to anosmia, congestion, cough, fatigue, fever, headache, lethargy, myalgias, nausea, progressive weakness, and shortness of breath that were treated in an outpatient setting. the mean duration of covid-19 symptoms in these 9 patients was 9.89 days. the most common treatment for covid-19 infection was acetaminophen (60%) followed by azithromycin (40%) and hydroxychloroquine (20%). overall, the average onset of hair shedding was 73 days after initial covid-19 symptoms. the most common pattern of hair loss was diffuse hair thinning (80%) followed by bitemporal recession and thinning (50%). while over the counter minoxidil solution or foam was recommended to four of the patients, most did not receive any further treatment. at 14week follow-up, 50% of the patients’ hair complaints had resolved. a total of 28 patients with te following laboratory confirmed covid-19 infection were identified across five retrospective studies, case reports, and case series. data analysis including patient demographics, medical intervention for covid-19, duration of illness, time between covid-19 infection and onset of hair loss, physical exam findings, treatment for telogen effluvium, and outcomes are summarized in tables 2 and 3. half of the patients who developed te were hospitalized for treatment of severe covid-19, while 35.7% of the patients experienced mild to moderate symptoms only. the average time between covid-19 infection and onset of te was 87 days with a standard deviation of 48 days. most patients (82.1%) did not have any previous history of hair loss, while all others had a history of androgenic alopecia (aga) or female pattern androgenic alopecia (faga). the time between the stressor and onset of hair loss in telogen effluvium is equivalent to the length of the telogen phase, or approximately 3 months.2,3 consistent with this, the patients reported in methods results discussion https://paperpile.com/c/oo8g4l/lmw2+5dzw skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 535 table 1. summary of patients with covid-19 induced telogen effluvium age (years) 20 26 28 32 56 56 58 61 63 68 gender female male female female female male female male female male race white white white white white unspecified white white white unspecified comorbidities none none none none htn htn hld none htn hld dm none htn covid-19 symptoms congestion cough fatigue anosmia cough fever fatigue fever headache anosmia cough fatigue fever myalgias nausea progressive weakness sob congestion cough fatigue fever lethargy sob anosmia cough fatigue fever nausea sob cough fever myalgias sob cough fatigue fever myalgias sob anosmia diarrhea fatigue fever progressive weakness sob cough fatigue fever sob disposition op op op op op op op inpt op op medical intervention for covid-19 albuterol ics none apap apap apap azm apap ibp apap azm azm hcq mv azm hcq apap duration of illness (days) 7 5 7 8 21 10 8 40 7 16 days between covid-19 infection and telogen onset 84 70 84 84 105 56 21 28 112 84 physical exam findings bitemporal recession diffuse hair thinning positive telogen hair pull test microscopy temporal hair thinning diffuse hair thinning throughout diffuse hair thinning throughout bitemporal recession diffuse hair thinning positive telogen hair pull test microscopy left sided temporal hair thinning diffuse hair thinning diffuse hair thinning diffuse hair thinning bitemporal recession, diffuse hair loss treatment for telogen effluvium minoxidil 5% solution none minoxidil 5% solution minoxidil 5% solution none none minoxidil 5% foam none none none outcome* resolved unresolved resolved resolved unresolved resolved unresolved unresolved unresolved resolved apap= acetaminophen, azm= azithromycin, dm= diabetes mellitus, hcq= hydroxycholorquine, hld= hyperlipidemia, htn= hypertension, ibp= ibuprofen, ics= inhaled corticosteroids, inpt= inpatient, mv= mechanical ventilation, op= outpatient, *outcome measured at 14 weeks this case series developed hair loss on average 73 days after infection with covid19. other reported cases of post covid-19 telogen effluvium presented with similar timing. common causes of te include medications, physiological stress, medical conditions, and metabolic imbalances.2 associations between acute te and severe viral infections such as dengue, human immunodeficiency virus, and influenza have been previously reported, although the mechanism by which this occurs is largely unknown.4-6 proposed mechanisms range from primary follicle infection by causal virus to metabolic disturbances in hair follicle cells.4,5 given the consistency in timing and presentation of our patients and those reported in the literature, it may be inferred that there is a correlation between covid19 infection and the development of te. while the mechanism behind te in patients infected by covid-19 has not yet been elucidated, olds h et. al. proposed that the combination of increased proinflammatory cytokines and consumption of anticoagulant proteins observed in severe covid-19 infection lead to systemic inflammation and microthrombi formation, leading to occlusion of arterial hair supply.3 this proposal was made to explain te in severe cases of covid-19, where most patients were hospitalized.3 nearly half of the patients that developed te, as identified in our review, https://paperpile.com/c/oo8g4l/lmw2 https://paperpile.com/c/oo8g4l/agx7 https://paperpile.com/c/oo8g4l/5dzw+0k8i https://paperpile.com/c/oo8g4l/83ls https://paperpile.com/c/oo8g4l/83ls skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 536 were similarly hospitalized for serious covid-19 infections. table 2. reported cases of post covid-19 te: summary of patient demographics total number of patients with confirmed post covid-19 te 28 age (years), mean ± sd 52.1 ± 15.0 gender, n (%) female 27 (96.4%) male 1 (3.6%) race, n (%) white 7 (25.0%) black 6 (21.4%) middle eastern 1 (3.6%) unspecified 14 (50.0%) disposition, n (%) patient hospitalized, n (%) 14 (50.0%) outpatient 10 (35.7%) unspecified 4 (14.3%) medical intervention for covid 19, n (%) azithromycin 6 (21.4%) ceftriaxone 5 (17.9%) doxycycline 2 (7.1%) other antibiotics* 3 (10.7%) hydroxychloroquine 7 (29.2%) oral corticosteroids 3 (10.7%) enoxaparin and lopinavir/ritonavir 3 (10.7%) chlorphenamine 1 (3.57%) tocilizumab 1 (3.57%) supportive 2 (7.1%) none 7 (29.2%) unspecified 4 (14.3%) sd= standard deviation, *not specified by authors however, the majority of the te patients described in this case series experienced mild covid-19 symptoms. although hospitalizations and serious illness are known causes of telogen effluvium, mildto-moderate illness not requiring extensive medical intervention does not usually cause notable hair loss. proteomic analysis comparing the serum of patients with active covid-19 infections compared to healthy donors identified significant changes in inflammatory cytokines (e.g., cxcl6) and proteins associated with immune cell activation (e.g., cd244 and cd40) between the two groups.8 in comparison, proteomic expression mild and severe covid-19 patients do not demonstrate the same variability, implying high immune activation even in mildly symptomatic patients. as te can be caused by a surge of inflammation, increased severity of covid-19 infection does not necessarily correlate with increased risk for developing postinfectious te. literature on dengue fever associated te similarly found no association between severity of infection and hair loss.3,9 additionally, coagulopathy studies of covid-19 patients revealed coagulation functions remained fairly stable in mild covid-19 and not significantly different from baseline (convalescent state) within the same individuals.10 the presence of te in mild covid-19 patients may suggest that elevated inflammatory cytokines play a larger role in the accelerated transition from anagen to telogen phase. the theory proposed by olds h et. al. of arterial hair supply occlusion by microthrombi secondary to a hypercoagulable state 7 may not be as contributory to the development of te in covid patients. te induced by azithromycin, hydroxychloroquine or other medications used to treat covid-19 should be considered in these cases, though this association has not been previously reported. it should be noted that anticoagulants such as heparin have been implicated as a trigger for te, and all three patients reported by rizzetto et. al. were treated with enoxaparin during their hospitalization which could confound causal analysis.11 patients with pre-existing te have reportedly experienced worsened hair loss associated with the increased psychosocial stress induced by mandated quarantine. psychological and emotional stressors are a known trigger for te, so they may contribute to the new onset te seen in covid-19 patients. as our sample size is limited, we are unable to definitively determine a causal relationship between covid infection and te. https://paperpile.com/c/oo8g4l/syjj https://paperpile.com/c/oo8g4l/5dzw+p8m0 https://paperpile.com/c/oo8g4l/83ls https://paperpile.com/c/oo8g4l/z0ba skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 537 table 3. reported cases of post covid-19 te: summary of clinical findings onset of te related to covid-19 infection mean (days) ± sd 87.1 ± 47.7 range (days) (21, 210) history of hair loss, n (%) aga 1 (3.6%) faga 4 (14.3%) none 23 (82.1%) te physical exam findings, n (%) positive telogen hair pull test 10 (35.7%) increased shedding 7 (25.0%) diffuse hair thinning 10 (35.7%) aga= androgenic alopecia, faga= female androgenic alopecia, sd= standard deviation though the consistent timing of te after recovery and the numerous case reports cited may suggest such a relationship exists. previous studies report that most cases of covid-19-related te occur in patients with severe infections, our investigation demonstrates that this phenomenon may also occur in mild to moderate cases of covid-19. this is of particular relevance for dermatologists practicing in communities greatly affected by covid-19, as they should expect to see a directly correlated increase in telogen effluvium cases in the months to follow. patients should be educated on the increasing evidence of a causal link between te and covid-19 infection as well as reassurance regarding the self-limiting nature of the disease. the link between telogen effluvium and covid19 is still under evaluation, and further studies are needed to identify a causal relationship. conflict of interest disclosures: none funding: none corresponding author: nancy wei, ba icahn school of medicine at mount sinai 5 east 98th street, 5th floor new york, ny 10029 phone: 212-241-9728 email: nww27@drexel.edu references: 1. mieczkowska, k. et al. telogen effluvium: a sequela of covid-19. int. j. dermatol. 60, 122– 124 (2021). 2. asghar, f., shamim, n., farooque, u., sheikh, h. & aqeel, r. telogen effluvium: a review of the literature. cureus 12, e8320 (2020). 3. olds, h. et al. telogen effluvium associated with covid-19 infection. dermatol. ther. e14761 (2021). 4. wei, k.-c., huang, m.-s. & chang, t.-h. dengue virus infects primary human hair follicle dermal papilla cells. front. cell. infect. microbiol. 8, 268 (2018). 5. chu, c.-b. & yang, c.-c. dengue-associated telogen effluvium: a report of 14 patients. dermatologica sinica 35, 124–126 (2017). 6. bernstein, g. m., crollick, j. s. & hassett, j. m., jr. postfebrile telogen effluvium in critically ill patients. crit. care med. 16, 98–99 (1988). 7. olds, h. et al. telogen effluvium associated with covid-19 infection. dermatol. ther. e14761 (2021). 8. su, y. et al. multi-omics resolves a sharp disease-state shift between mild and moderate covid-19. cell 183, 1479 (2020). 9. tristão-sá, r. et al. clinical and hepatic evaluation in adult dengue patients: a prospective two-month cohort study. rev. soc. bras. med. trop. 45, 675– 681 (2012). 10.tan, c. w. et al. clinical and laboratory features of hypercoagulability in covid-19 and other respiratory viral infections amongst predominantly younger adults with few comorbidities. sci. rep. 11, 1793 (2021). 11. harrison, s. & bergfeld, w. diffuse hair loss: its triggers and management. cleve. clin. j. med. 76, 361–367 (2009). conclusion http://paperpile.com/b/oo8g4l/utvm http://paperpile.com/b/oo8g4l/utvm http://paperpile.com/b/oo8g4l/utvm http://paperpile.com/b/oo8g4l/utvm http://paperpile.com/b/oo8g4l/utvm 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http://paperpile.com/b/oo8g4l/p8m0 http://paperpile.com/b/oo8g4l/p8m0 http://paperpile.com/b/oo8g4l/p8m0 http://paperpile.com/b/oo8g4l/p8m0 http://paperpile.com/b/oo8g4l/p8m0 http://paperpile.com/b/oo8g4l/p8m0 http://paperpile.com/b/oo8g4l/p8m0 http://paperpile.com/b/oo8g4l/p8m0 http://paperpile.com/b/oo8g4l/p8m0 http://paperpile.com/b/oo8g4l/zeyg http://paperpile.com/b/oo8g4l/zeyg http://paperpile.com/b/oo8g4l/zeyg http://paperpile.com/b/oo8g4l/zeyg http://paperpile.com/b/oo8g4l/zeyg http://paperpile.com/b/oo8g4l/zeyg http://paperpile.com/b/oo8g4l/zeyg http://paperpile.com/b/oo8g4l/zeyg http://paperpile.com/b/oo8g4l/zeyg http://paperpile.com/b/oo8g4l/zeyg http://paperpile.com/b/oo8g4l/zeyg http://paperpile.com/b/oo8g4l/z0ba http://paperpile.com/b/oo8g4l/z0ba http://paperpile.com/b/oo8g4l/z0ba http://paperpile.com/b/oo8g4l/z0ba http://paperpile.com/b/oo8g4l/z0ba http://paperpile.com/b/oo8g4l/z0ba http://paperpile.com/b/oo8g4l/z0ba skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 307 brief article lobular panniculitis in a patient with chronic lymphoid leukemia melissa cheng, bs1, diem q. pham, do1,3, gene h. kim, md2 1 western university of health sciences college of osteopathic medicine of the pacific, pomona, ca 2 university of southern california keck school of medicine, department of dermatology, los angeles, ca 3 san dermatology, chino hills, ca panniculitis is the inflammation of the subcutaneous fat layer that results in painful nodules under the skin. it is classified into septal and lobular categories with and without vasculitis[1]. clinically, panniculitis presents as deep seated, red, edematous nodules or plaques that is often the manifestation of internal disease[2]. there are many subtypes of panniculitis with etiologies due to infection, trauma, malignancy, deposition, enzymatic destruction, and inflammatory disease[3]. diagnosis is made from histopathological findings and clinical presentation[2]. this case report discusses a patient with lobular panniculitis without vasculitis associated with chronic lymphoid leukemia (cll). a 63-year-old caucasian female with chronic lymphoid leukemia (cll) initially presented to the dermatology clinic with pink, erythematous nodules on the left lower leg in 2018. she has a history of ductal carcinoma in situ and paget’s disease. a punch biopsy was performed and demonstrated a focal lobular panniculitis on the left lower leg. beneath a mostly unremarkable epidermis and dermis, there was a focal infiltrate present within the lobules of the subcutis as shown in figure 1. at the time, the patient was receiving abt199, a clinical trial medication, to treat cll. the patient was treated with clobetasol 0.05% topical cream and lesions resolved. the patient returned to clinic again in june 2021 reporting the onset of new, pink, erythematous, indurated, subcutaneous nodules on the right lower leg. (figure 2) the patient reported moderate to severe pain and inflammation. she has been receiving duvelisib for the past 6 months to treat the cll. the patient was treated with kenalog 20 mg/ml intralesional injections in abstract panniculitis is the inflammation of the subcutaneous fat that presents as red, painful nodules under the skin and may be a manifestation of internal disease. causes of lobular panniculitis include systemic lupus erythema, pancreatic disorders, α1-antitrypsin deficiency, or infection. this case discusses a 63year-old female that presents with lobular panniculitis without vasculitis associated with chronic lymphoid leukemia. though cutaneous manifestations due to chronic lymphoid leukemia are not uncommon, it is rare to see panniculitis associated with chronic lymphoid leukemia. introduction case report skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 308 figure 1. beneath a mostly unremarkable epidermis and dermis, there is a small focus within the subcutis containing a lobular lymphohistiocytic infiltrate (400x) the right and left lower leg and was prescribed clobetasol 0.05% topical cream. due to thrombocytopenia, a biopsy could not be performed. to rule out common panniculitis etiologies due to α1-antitrypsin deficiency, pancreatitis, tuberculosis, and systemic lupus erythema, laboratory testing was performed. the patient was negative for antinuclear antibody (ana), rheumatoid factor, quantiferon-tb gold, and α1antitrypsin, ruling out the above listed common etiologies. upon follow up visit, lesions showed improvement. (figure 3) lobular panniculitis without vasculitis is a subtype of panniculitis that is characterized histologically by few or no inflammatory cells and damage to fat nodules in the subcutis layer[2]. most commonly, lobular panniculitis without vasculitis is due to sclerosing panniculitis, calciphylaxis, cold panniculitis, systemic lupus erythematous, pancreatic disease, α1-antitrypsin deficiency, dermatomyositis, infections or trauma[3]. histological differences can be identified due to the varying etiologies. figure 2. lesions on right lower leg at initial visit in june 2021 lupus panniculitis is classified by lymphoid follicles, and nuclear dust of lymphocytes. α1antitrypsin deficiency is classified by neutrophils between collagen bundles of the deep reticular dermis. sclerosing panniculitis is classified by necrosis at the center of the lobule and pancreatic panniculitis is classified by extensive fat necrosis with saponification of adipocytes[3]. these histological differences, along with varying clinical presentations, aid in diagnosis of panniculitis and it’s underlying cause. the patient’s biopsy results were non-specific for panniculitis. chronic lymphoid leukemia is an adult leukemia characterized by increased cd5+ and cd23+ b cells in the blood, marrow, and secondary lymphoid tissues and is the most common adult leukemia in the western world[4]. it is a lymphoproliferative disorder that is initially detected by increased lymphocyte count or b symptoms[4]. cll presents with primarily hematological manifestations but there have been cases of discussion skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 309 initial cutaneous presentations of cll. in a case series, patients presented with figure 3. lesions on right lower leg at follow up visit in july 2021 erythematous plaques, angiomatosis/telangiectasia and erosive skin changes and histological analysis indicated underlying lymphoma in these cases of undiagnosed patients[5]. additionally, skin complications in patients with established cll are fairly common with patients presenting with basal cell carcinoma, squamous cell carcinoma, leukemia cutis, and cutaneous drug eruptions[6]. 25% of patients diagnosed with cll can later present with skin lesions, with leukemia cutis making up 4-27% of those lesions[7]. leukemia cutis presents as lumps and bumps of various sizes or erythematous lesions, petechiae, ulcerations, blisters with dissemination across the entire body[7]. it is uncommon to have panniculitis due to chronic lymphoid leukemia. panniculitis has been documented as a paraneoplastic occurrence, appearing in gi malignancies. there are cases reporting panniculitis as a result of pancreatic carcinoma [8]. a retrospective review found that in 11 patients with panniculitis, five had pancreatitis and six had pancreatic carcinoma [9]. though it is not uncommon that panniculitis can be due to gi malignancy, it is unique that it is due to a hematological one. documented cases of cll patients with panniculitis have been due to the adverse events related to the treatment ibrutinib[10]. in this case, the patient is on duvelisib for treatment of cll and panniculitis has not been linked to duvelisib usage. the most common adverse events of duvelisib usage are neutropenia, diarrhea/colitis, and infection[11]. the patient has not been on ibrutinib treatment, so it is unlikely the lesions are caused by a known drug induced adverse event. the outcome of panniculitis is a result of the underlying cause of inflammation. in addition to treating the underlying cause, treatment can involve use of nonsteroidal antiinflammatory drugs (nsaids) or systemic steroids to settle inflammation. in this case, nsaids were not given due to interference with the patient’s current cll treatment. thus, lesions were treated topically via 0.05% clobetasol cream and via 20 mg/ml kenalog intralesional injection with improvement during the follow up visit. however, reoccurrence is possible because the underlying cause is associated with cll and there have already been previous occurrences of panniculitis. while cutaneous manifestations of chronic lymphoid leukemia are not uncommon, panniculitis is not a common presentation. this case documents a patient with lobular panniculitis without vasculitis as a symptom conclusion skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 310 of her cll with other common etiologies ruled out. though reoccurrence is likely because of the association with cll, upon local treatment, lesions improved which increased the patient’s quality of life by decreasing pain and discomfort. conflict of interest disclosures: none funding: none corresponding author: melissa cheng, bs 3110 chino ave #120 chino hills, ca 91709 melissa.cheng@westernu.edu references: 1. ter poorten, m.c. and b.h. thiers, panniculitis. dermatol clin, 2002. 20(3): p. 421-33, vi. 2. diaz cascajo, c., s. borghi, and w. weyers, panniculitis: definition of terms and diagnostic strategy. am j dermatopathol, 2000. 22(6): p. 530-49. 3. requena, l. and e. sánchez yus, panniculitis. part ii. mostly lobular panniculitis. j am acad dermatol, 2001. 45(3): p. 325-61; quiz 362-4. 4. scarfò, l., a.j.m. ferreri, and p. ghia, chronic lymphocytic leukaemia. critical reviews in oncology/hematology, 2016. 104: p. 169-182. 5. plaza, j.a., et al., unusual cutaneous manifestations of b-cell chronic lymphocytic leukemia. journal of the american academy of dermatology, 2009. 60(5): p. 772-780. 6. agnew, k.l., et al., cutaneous findings in chronic lymphocytic leukaemia. br j dermatol, 2004. 150(6): p. 1129-35. 7. szukalski, ł., et al., cutaneous manifestation of chronic lymphocytic leukemia: a case report and a literature review. postepy dermatol alergol, 2019. 36(6): p. 778-780. 8. pan, w., et al., pancreatic carcinoma presented with panniculitis and polyarthritis: a rare case. j cancer res ther, 2021. 17(7): p. 1751-1754. 9. dahl, p.r., et al., pancreatic panniculitis. j am acad dermatol, 1995. 33(3): p. 413-7. 10. fabbro, s.k., et al., panniculitis in patients undergoing treatment with the bruton tyrosine kinase inhibitor ibrutinib for lymphoid leukemias. jama oncology, 2015. 1(5): p. 684686. 11. frustaci, a.m., et al., duvelisib for the treatment of chronic lymphocytic leukemia. expert opin pharmacother, 2020. 21(11): p. 1299-1309. mailto:melissa.cheng@westernu.edu mailto:melissa.cheng@westernu.edu keratolytic activity of a novel topical dimethicone formulation (pb/lo-112) compared to 10% salicylic acid oil in patients with psoriasis capitis arnd jacobi, anke mayer, zografia anastasiadou, matthias augustin institute for health services research in dermatology and nursing, university medical center hamburg-eppendorf, germany background psoriasis is a common chronic inf lammatory skin disease most commonly characterized by welldemarcated, erythematous plaques with silver scales and associated with a number of comorbidities. globally, the prevalence of psoriasis reported in population-based studies in adults ranges from 1% to 8.5%, with differences based on geographic location.1 many patients with psoriasis feel stigmatized and suffer from marked physical and psychological disease burden, contributing to significant reductions of quality of life (qol). the scalp is one of the most common sites of psoriasis, affecting 50–80% of patients.2 treatment can be burdensome and includes keratolysis of plaques followed by anti-inf lammatory measures. keratolysis with salicylic acid in oily vehicles is effective but burdensome and inconvenient to many patients. loyon® (pb/lo-112) is a unique, patented combination of the dry emollient cetiol® cc and the medical silicone oil dimethicone. the combination of the 2 substances gives loyon® a low surface tension as well as high creep and spreading properties. the liquid is very easily applied and allows a gentle yet effective lifting of scales. the objective of this study was to evaluate the efficacy, safety, and patient acceptance for this novel topical formulation (pb/lo-112) compared to 10% salicylic acid (10-sa) for the removal of scaling in patients with chronic psoriasis capitis. objectives results there was a statistically significant reduction of scaling score after 7 days in both treatment groups (pb-lo/112: baseline [mean±sd] 2.8±0.7, day 7=2.2±0.7, p<0.001; 10-sa: baseline [mean±sd] 2.9±0.8, day 7=2.1±0.8, p<0.001) in both groups and non-inferiority (p=0.91 for the intent to treat and p=0.83 for the per protocol population) for pb-lo/112 compared with 10-sa. for the secondary endpoint of scalp physician global assessment (spga), the response was equivalent in the 2 groups. however, the pblo/112 group saw a faster onset of keratolytic effect than the 10-sa group. efficacy (pssi scaling score) methods in this single-center, randomized, active-controlled, observer-blinded, parallel group trial, 90 patients with chronic psoriasis capitis were randomized equally into 2 groups: one receiving the dimethicone formulation loyon® (test group) and the other receiving a topical 10% salicylic acid formulation (10-sa, standard group). primary outcomes parameter was the improvement of scaling of the psoriasis scalp severity index (pssi). minimum clinical response was defined as at least 0.5 units improvement on the pssi scaling score [0-4] at day 7 after daily application. secondary outcomes were the scalp physician global assessment (spga), patient quality of life (dlqi) and patient acceptance and tolerability by pbi, eq-5dvas and eq-5d. for control reasons, the overall pasi was assessed and a second observer-blinded analysis was conducted after photo documentation. the effectiveness of pb/lo-112 was statistically tested for non-inferiority to 10-sa. the primary endpoint analysis (improvement of ≥0.5 points in pssi scaling scores) after 7 days demonstrated that the pb/lo-112 group was non-inferior to 10-sa group (p = 0.83 for the pp population), thereby providing evidence of equivalent efficacy of pb-lo/112. (figure 1) pssi erythema and infiltration scores showed highly significant improvement in both groups compared to baseline as well as the spga score (data not shown). relative reduction of pssi was in favor of pb-lo/112 after 3 treatment days (25% for pb-lo/112 vs.14% for 10-sa; and increased for pb-lo/112 to 38% after 7 days, while 10-sa remained on the initial level. (figure 2) safety for pb-lo/112 and 10-sa, in total 13 adverse events (aes) in 10 patients were reported. eight aes were mild, 4 were moderate and 1 (i.e., an allergic reaction of severe intensity which appeared in the 10-sa group) was severe. the most frequently reported aes were erythema (n=3) and itching (n=3). two aes led to premature discontinuation. the vast majority of patients (71 %) reported aes only at day 7 or later. there were no serious aes. patient reported outcomes for patient benefit and quality of life determined with the pbi, dlqi and eq-5d questionnaire, an improvement from baseline to visit 3 (day 7) was observed in both groups. the difference in improvements between the 2 groups was not statistically significant. compliance to treatment instructions was generally described as very good by physicians in both treatment groups. conclusion pb/lo-112 and 10-sa show comparable efficacy with respect to desquamation of scalp psoriasis, with a time advantage for pb/lo-112. in the light of excellent safety and very good patient acceptance, this dimethicone formulation might be an alternative to conventional keratolytics figure 3. photographs of the scalp of a 19-year-old patient with pronounced scalp psoriasis (a [left]) at baseline and (b [right]) after treatment with pb-lo/112 once daily for 7 days. a significant improvement of scaling is seen. references 1.michalek im, loring b, john sm. a systematic review of worldwide epidemiology of psoriasis j eur acad dermatol venereol. 2017;31(2):205. 2. schön mp, henning boehncke w-h. medical progress: psoriasis. n engl j med 2005;352:1899-912. figure 2. psoriasis scalp severity index (relative reduction) r el at iv e r ed uc tio n -40% -35% -30% -25% -20% -15% -10% -5% 0% loyon sa psoriasis scalp severity index pssi day 3 day 7 figure 1. improvement in scaling after 7 days sc al in g im pr ov em en t: pe rc en t o f p at ie nt s 0.00% 10.00% 20.00% 30.00% 40.00% 50.00% 60.00% 1 pb / lo 112 10-sa a b fc17posterintradermjacobikeratolyticactivity.pdf skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 138 brief article wells syndrome with sustained response to omalizumab kezia surjanto, bs1, gage rensch, md1, garrett vick, md1, andrea murina, md1 1tulane university school of medicine, new orleans, la wells syndrome (eosinophilic cellulitis) is a rare dermatosis characterized by pruritic and erythematous plaques, papules, vesicles, or blisters that commonly appear on the extremities. autoimmunity, insect bites, drugs, contact allergens, infections, and photosensitivity are triggers that have previously been associated with this diagnosis.1 treatment options for wells syndrome include corticosteroids, antihistamines, antibiotics, immunosuppressants, and biologics.2 we present a case of wells syndrome that was unresponsive to corticosteroids, antivirals, antibiotics, antihistamines, and dapsone. this case reflects one of the few reported instances of wells syndrome that was successfully treated with omalizumab. a 39-year-old female with no significant past medical history presented with a three-year history of small pruritic papules located on the face, extremities, and genitals (figure 1). figure 1. abstract wells syndrome (eosinophilic cellulitis), a rare dermatosis that arises from a multitude of triggers, may present with pruritic and erythematous plaques, papules, vesicles, or blisters.1 we present a case of wells syndrome that was successfully treated with omalizumab. a 39-year-old female presented with a three-year history of diffusely located pruritic papules. after a negative lab and infectious workup, a punch biopsy showed dense eosinophilic infiltrate in the dermis as well as “flame figure” formation. unsuccessful trials of prednisone, cetirizine, hydroxyzine, and dapsone prompted the use of omalizumab, which yielded excellent control of symptoms. omalizumab’s success in the wells syndrome disease process may be explained by its anti-inflammatory effects on ige autoantibodies and receptors.5 few cases of wells syndrome treated with omalizumab have been reported. thus, increased research to thoroughly elucidate omalizumab’s pharmacological mechanism of action in this particular disease process is warranted and would be a valuable contribution to the wells syndrome literature. introduction case report skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 139 further review of systems was negative. prior to initial presentation, she trialed valacyclovir, clobetasol, mupirocin, and loratadine without improvement. previous labs showed negative ana and a normal eosinophil count. at the first visit, she was prescribed betamethasone ointment and an increased dose frequency of loratadine from once to twice a day. a scraping for scabies was negative, which prompted a punch biopsy of the left lower arm. biopsy sections showed a dense infiltrate in the dermis with abundant eosinophils (figure 2) figure 2. as well as characteristic “flame figure” formation (figure 3) that supported a diagnosis of wells syndrome. at follow up, the patient noted progression of her symptoms with a new plaque on the right hip and new pruritic papules arising on a weekly basis. she was started on prednisone 60 mg daily with a month-long taper, daily cetirizine and nightly hydroxyzine. although her skin cleared with the medications, her symptoms flared once the prednisone dose was tapered to 10 mg. figure 3. she was then started on dapsone 50 mg daily, which decreased the tenderness of her lesions and the frequency of her flares. nine months after taking dapsone, the patient reported decreased grip strength in her right hand, which affected her work as an aesthetician. to avoid worsening of musculoskeletal sequelae, dapsone was discontinued and she was referred to neurology. the patient was then started on omalizumab 150 mg subcutaneously every 28 days. the patient tolerated the omalizumab injections well, reporting no more than one flare of her skin in between injections and an overall improvement without any reported side effects. this patient has been on omalizumab for over 9 months now with excellent control of her symptoms. skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 140 table 1. summary of wells syndrome cases successfully treated with omalizumab. there are seven reported cases to date, including the present case report. data from this table are from egeland et al2, ogueta et al3, and coattrenec et al6. case report age sex presenting symptoms mean time to presentation medications trialed omalizumab regimen mean time to resolution treatment length egeland et al 45 female painful and pruritic deep erythematous noduli and plaques (several ulcerated) on ears, back, hands, and scalp 10 years antihistamines prednisolone cyclosporine dapsone colchicine 300 mg every 4 weeks 3 months 13 months ogueta et al 71 male acute cutaneous eruption of pruritic and painful erythematous and edematous plaques 15 years bilastine 80 mg prednisone colchicine dapsone cyclosporine 300 mg every 4 weeks 6 weeks asymptomatic after 20 months ogueta et al 62 female painful erythematous and indurated plaques on trunk and legs 20 years bilastine 40 mg 300 mg every 4 weeks 8 weeks asymptomatic after 18 months ogueta et al 71 female persistent plaques on trunk and extremities, and hyperpigmented macules 1 year bilastine 80 mg prednisone 30 mg 300 mg every 3 weeks + bilastine 60 mg daily, then 300 mg every 4 weeks + bilastine 20 mg daily 16 weeks free of lesions on omalizumab 300 mg every 4 weeks + bilastine 20 mg daily ogueta et al 61 female deep pruritic and hot erythematous plaques 15 years prednisone 30 mg deflazacort 30 mg rupatadine 20 mg dapsone 100 mg 300 mg every 4 weeks, then 300 mg every 6 weeks 1 week asymptomatic after 1 year coattrenec et al 67 male erythema and occasional edema of the limbs, tongue, and face 30 years antihistamines corticosteroids (topical and systemic) azathioprine 150 mg tranexamic acid 1000 mg 300 mg every 4 weeks, then 300 mg every 8 weeks dramatic improvement after a few days asymptomatic after 24 months surjanto et al 39 female pruritic papules on face, extremities, and genitals plaque on hip 3 years valacyclovir clobetasol mupirocin loratadine prednisone 60 mg, tapered to 10 mg cetirizine hydroxyzine dapsone 50 mg 150 mg every 28 days 8 weeks asymptomatic for over 9 months skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 141 wells syndrome is an uncommon dermatosis believed to be a type iv hypersensitivity reaction.2,3 although many variants of wells syndrome have been observed, characteristics such as pruritic and tender erythematous plaques on gross observation, along with dermal infiltrate of eosinophils with “flame figures” on histology, tend to be suggestive of the diagnosis.2,3 said “flame figures” represent aggregates of major basic protein released from eosinophils which disintegrate the structural integrity of surrounding collagen and subsequently destroy local tissue.1 in addition to characteristic histological features, wells syndrome criteria that were seen in our patient also include a recurrent course of cutaneous manifestations, no evidence of triggering factors, and inconsistent blood eosinophilia.4 previously reported treatments for wells syndrome are vast, ranging from corticosteroids to biologics.2 however, there are only a handful of papers that report the use and efficacy of omalizumab. omalizumab is a monoclonal antiimmunoglobulin e (ige) antibody that was first approved for the treatment of persistent allergic asthma, then later for the treatment of refractory chronic spontaneous urticaria.5 the current knowledge of omalizumab on cutaneous inflammatory diseases is that the drug decreases ige levels, ige receptors, mast cells’ ability to release contained substances, and the action of ige autoantibodies against autoantigens.5 despite ongoing speculation on the drug’s anti-inflammatory pathways, treatment of wells syndrome with omalizumab has been shown to be effective.2,3,6 to date, our case is the seventh case of wells syndrome that was successfully treated with omalizumab (table 1). although it is imperative that more research be done to elucidate omalizumab’s pharmacological mechanism of action on the specific pathology of wells syndrome, omalizumab may be an effective treatment option for refractory cases of this disease. this case report aims to highlight another instance of omalizumab’s success to add to the wells syndrome literature. conflict of interest disclosures: none funding: none corresponding author: kezia surjanto 1430 tulane avenue new orleans, la 70112 email: ksurjanto@tulane.edu references: 1. weins ab, biedermann t, weiss t, weiss jm. wells syndrome. jddg: journal der deutschen dermatologischen gesellschaft. 2016;14(10):989-993. 2. egeland ø, balieva f, undersrud e. wells syndrome: a case of successful treatment with omalizumab. int j dermatol. 2018;57(8):994-995. 3. ogueta i, spertino j, deza g, et al. wells syndrome and chronic spontaneous urticaria: report of four cases successfully treated with omalizumab. j eur acad dermatol venereol. 2019;33(10). 4. caputo r, marzano av, vezzoli p, lunardon l. wells syndrome in adults and children: a report of 19 cases. arch dermatol. 2006;142(9). 5. kaplan ap, giménez-arnau am, saini ss. mechanisms of action that contribute to efficacy of omalizumab in chronic spontaneous urticaria. allergy. 2017;72(4):519-533. 6. coattrenec y, ibrahim yasmine l, harr t, spoerl d, jandus p. long-term remission of wells discussion conclusion skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 142 syndrome with omalizumab. j investig allergol clin immunol. 2020;30(1):58-59. skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 274 clinical management recommendation clinical management of actinic keratosis: review and update haowei han, do1, daniela k. berman, aa2, brian berman md, phd1, 3 1 center for clinical and cosmetic research, miami, fl 2 university of california berkeley plant gene expression center, university of california, berkeley, berkeley, ca 3 department of dermatology and cutaneous surgery, university of miami, miami, fl actinic keratosis (ak), also known as senile keratosis or solar keratosis, was first described by dubreuilh in 1826.1 later in 1958, pinkus renamed this lesion as actinic keratoses.1 2 ak literally means thickened, scaly growth caused by electromagnetic radiation.3 it commonly presents as illbordered macules, papules or plaques, maybe covered with dry scales or showing varying degree of hyperkeratosis. the color of ak ranges from pink to erythematous to brownish, in cases of pigmented ak. ak frequently locates at the sun exposed area, and sometimes, they are better pinpointed by palpation than visualization.4 in majority of the cases, ak are asymptomatic albeit some patients may report burning or pruritus sensation.1 5 the key risk factor for developing ak is cumulative sun exposure.6 an epidemiology study in turkey with 54,786 patients from outpatient dermatology clinic found that the ak prevalence was 4.61% for patients between 60 and 69 years old, 9.38% for patients between 70 and 79 years old, and 14.57% for patients ≥80 years old. ak prevalence was 2.50% across all age groups.5 the author concluded that ak prevalence was higher in patients >60 years of age and most commonly in patients >80 years of age. furthermore, ak was more prevalent in males and in patients with fitzpatrick skin types 2 and 3.5 another epidemiology study in netherlands examined various risk factors and revealed that male sex, the age of 70 years or older, glogau scale 3 and 4, and the tendency to develop sunburn were significantly associated with the development ak.7 on dermoscopic examination, nonpigmented facial aks typically manifests as a “strawberry pattern” which entails an erythematous vessel pseudo network, prominent follicular openings, and a surrounding white halo.4 a few histological and clinical subtypes of ak were described in the literature, for instance, hypertrophic, abstract actinic keratosis is commonly seen in dermatology clinics. age and chronic sun exposure are the essential risk factors for its pathogenesis. it is regarded as a premalignant lesion; hence, aggressive treatment is warranted. abundant research has been published about overall management, however, extensive knowledge about actinic keratosis prevention, the cost, safety profile, and mechanisms of the existing therapeutics are pivotal in optimal clinical care. in this review article, we hereby present several commonly used approaches in office settings and the current guidelines. finally, we will discuss the limitations of the available clinical evidence. introduction https://paperpile.com/c/0idjtl/jjli https://paperpile.com/c/0idjtl/jjli https://paperpile.com/c/0idjtl/1tkl https://paperpile.com/c/0idjtl/yumz https://paperpile.com/c/0idjtl/yout https://paperpile.com/c/0idjtl/jjli https://paperpile.com/c/0idjtl/1ede https://paperpile.com/c/0idjtl/vcjd https://paperpile.com/c/0idjtl/1ede https://paperpile.com/c/0idjtl/1ede https://paperpile.com/c/0idjtl/wp9i https://paperpile.com/c/0idjtl/yout skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 275 atrophic, ak with cutaneous horn, pigmented, actinic cheilitis, acantholytic, and hyperplastic.3 8 a common histological feature is atypical keratinocytic proliferation confined in the epidermis.3 it is regarded as the spectrum along the continuum to squamous cell carcinoma (scc).9 although the rate for individual ak to progress into scc is low, but 82.4% of sccs were developed from ak directly or from tissue that is adjacent to ak lesions.10 ak is principally caused by sun exposure, or ultraviolet b (uvb) radiation (wavelength 290–320 nanometer). particularly, uv-b induces the formation of thymine dimer in dna structures which leads to mutations in the telomerase gene and p53 gene, the tumor suppressor gene. telomerase is the key enzyme to regulate cellular death. increase in telomerase activity delays the programmed cell death and keeps cells immortal or keep proliferating unstoppably. neoplastic keratinocytes, which are seen in over 90% of invasive scc, are also frequently present in aks.11 12 p53 gene is located on chromosome 17p13 and normally arrest the cell cycle and allow the repair of damaged dna. dysregulation of p53 pathways results in the uncontrolled growth and proliferation of damaged keratinocytes, and potentially neoplastic cells. this is suggested to be an early phase in scc carcinogenesis, so that cancer can start to prosper and progress.12 a prospective large population study in california followed patients with and without ak (served as the control group) for 10 years and found the annual risk of acquiring scc for ak group was 1.92% compared to 0.83% for the control group. at the final 10 years end of study time point, the incidence of scc was 17.1% in ak group while the incidence of scc was 5.7% among control patients.6 with that being said, the early detection and treatment, patient education, and sun protection are critical for the overall management as well as efforts to decrease the healthcare burden. in this article, we herein present some approaches to prevent and manage ak based on the available literature and our own clinical experience. inarguably, sun protection is the most paramount approach to prevent not only ak but skin cancers as well. this conclusion was well established by several clinical trials.13 14 the american academy of dermatology (aad) website recommends patients avoid tanning beds and protect themselves by applying broad spectrum sunscreen daily with a spf (sun protection factor) of 30 or higher. it also emphasizes the cruciality of routine self-body skin check and dermatologist visits.15 studies have further investigated topical chemoprevention for ak. a randomized, placebo-controlled trial with 283 individuals showed that topical application of 5fluorouracil at the face and ears resulted 41% fewer new lesions at 24 months compared to placebo group.16 a similar study was reported with over 900 participants. patients were instructed to apply either 5% fluorouracil cream or placebo on the face or ears twice daily for up to 4 weeks. the treatment group had fewer non-hypertrophic ak lesions at 6month and 42-month follow-up visits. reciprocally, the number of hypertrophic ak didn’t differ significantly in both groups at 42month.17 a pooled analysis of two trials compared long term efficacy of imiquimod 5% cream and diclofenac 3% gel. the investigators observed superior result with imiquimod, 5% cream in multiple parameters, less percentage of histological changes to grade iii ak or even scc, greater time for neoplastic changes to occur, less proportion with malignant transformation into invasive scc, and lower ak recurrence rate.18 prevention https://paperpile.com/c/0idjtl/yumz https://paperpile.com/c/0idjtl/fiwn https://paperpile.com/c/0idjtl/yumz https://paperpile.com/c/0idjtl/ue6x https://paperpile.com/c/0idjtl/660w https://paperpile.com/c/0idjtl/myem https://paperpile.com/c/0idjtl/apxo https://paperpile.com/c/0idjtl/apxo https://paperpile.com/c/0idjtl/vcjd https://paperpile.com/c/0idjtl/jifv https://paperpile.com/c/0idjtl/js1r https://paperpile.com/c/0idjtl/lnar https://paperpile.com/c/0idjtl/vvwe https://paperpile.com/c/0idjtl/l3fu https://paperpile.com/c/0idjtl/uwlm skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 276 ak is often recognized as a field disease rather than a single clinically apparent lesion. the theory, field cancerization, contemplates that the skin proximal to ak lesions also carries a higher risk of malignancy due to shared chronic solar radiation.19 therefore, field treatments are commonly applied. it not only tackles the clinically perceptible lesions, but also the subclinical ones that may potentially progress into ak or even scc.20 cryotherapy is commonly used when there are only a handful of visible or palpable lesions. field treatment targets a certain anatomical region, including topical imiquimod, 5-fluorouracil (5fu), and photodynamic therapy (pdt). the commonly used monotherapies are listed in table 1. the treatment regimen for united states food and drug administration (fda) approved field therapies were listed in figure 1. single lesion liquid nitrogen cryotherapy cryotherapy, the mainstay treatment for ak, is fast, inexpensive and can be easily done in the office setting. either direct spray or probe may be used to deliver liquid nitrogen. the freezing time ranges from 5 to 10 seconds, and the “ice ball” should extend at least 1 millimeter beyond the clinical margin of ak. depending on the degree of hyperkeratosis, multiple freeze-thaw cycles may be required. cryotherapy causes local tissue damage and heals by secondary intention.21 with that being said, cryotherapy often leads to transient patient discomfort. other side effects may be seen in certain individuals, for instance, hypopigmentation, scaring, and prolong wound healing, thus, patient education and wound care instructions need to be provided for desired clinical outcomes.21 field treatment imiquimod imiquimod is an immune response modifier that belongs to the imidazoquinolines drug class and upregulates several key cytokines. it binds to the toll-like receptor 7 and releases interferon-alpha, which leads to activation of the t helper type 1 (th1) response. it has both anti-viral and antitumoral effects.22 23 in sum, imiquimod comes with three different concentrations and is only approved for immunocompetent individuals. the efficacy and the safety profile of imiquimod was well illustrated in several randomized phase iii clinical trials and metaanalyses.24 25 26 27 23 the most common side effects were treatment site reactions, such as erythema, ulceration, blistering, erosion, edema and influenza like symptoms.4 28 many of the side effects were well tolerated and short-lived. interestingly, case study has tried to apply 5% cream imiquimod on human skin to an area over 300 square centimeters (cm2), suggesting a more efficient use of this medication.29 tirbanibulin tirbanibulin works by inhibiting tubulin polymerization and upregulating p53 expression. it also arrests rapidly dividing cells at the interphase gap 2 and mitosis, subsequently induces apoptosis.30 in 2020, fda licensed topical tirbanibulin 1% ointment as a field treatment of ak to up 25 cm2 contiguous area of the face or scalp.31 the clinical data of tirbanibulin was found on two clinical management https://paperpile.com/c/0idjtl/xjp6 https://paperpile.com/c/0idjtl/t6iw https://paperpile.com/c/0idjtl/3y6p https://paperpile.com/c/0idjtl/3y6p https://paperpile.com/c/0idjtl/4uct https://paperpile.com/c/0idjtl/pr0d https://paperpile.com/c/0idjtl/gigm https://paperpile.com/c/0idjtl/qrol https://paperpile.com/c/0idjtl/xf5z https://paperpile.com/c/0idjtl/yqzu https://paperpile.com/c/0idjtl/pr0d https://paperpile.com/c/0idjtl/yout https://paperpile.com/c/0idjtl/sujy https://paperpile.com/c/0idjtl/gttv https://paperpile.com/c/0idjtl/layu https://paperpile.com/c/0idjtl/bf91 skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 277 figure 1. fda-approved, topical field therapies and total applications skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 278 table 1. commonly used monotherapies for single ak or field treatment (5-fu: 5 fluorouracil; ala: 5aminolevulinic acid; fda: food and drug administration; moa: mechanism of action, pdt: photodynamic therapy; rct: randomized clinical trials, se: side effects,)4 21 22 30 34 37 48 46 51 treatment moa side effects clinical evidence fda indication treatment regimen single lesion liquid nitrogen cryotherapy damage the tissue and re-epithelialize patient discomfort, hypopigmentation, scarring, and prolong wound healing. few meta-analysis and systematic review not available information freeze the clinically visible ak for 5-10 seconds per cycle. and the “ice ball” should extend at least 1 millimeter beyond the margin of ak. multiple freezethaw cycles may be required for thick lesions. wound care instruction will be provided to the patient. field treatment imiquimod 2.5% cream upregulate immune response treatment site reactions (erythema, ulceration, pruritus, blistering, erosion, edema), influenza like symptoms several phase iii rcts and metaanalysis. ak on the face or scalp in immunocompetent adults once per day overnight for about 8 hours x 2 weeks --> 2 weeks of treatment free period --> 2 weeks of treatment. imiquimod 3.75% cream ak on the face or scalp in immunocompetent adults once per day overnight for about 8 hours x 2 weeks --> 2 weeks of treatment free period --> 2 weeks of treatment. imiquimod 5% cream nonhyperkeratotic, non-hypertrophic ak on the face or scalp in immunocompetent adults one application/day, 2times/week x 16 weeks, maximum area of 25 cm2 per application 5-fu (varying concentration from 0.5% to 5%) cream or solution inhibiting dna and rna replication and increase expression of p53 treatment site reactions several phase iii rcts and metaanalysis. topical treatment of multiple ak apply cream or solution twice daily for 2-4 weeks. conventional pdt (10% 5aminolevulinic acid/methyl aminolevulinate + red light/blue light) photosensitizer is activated by light source and generates reactive oxygen species (ros), which causes selective cellular damage treatment site reactions, itchy, edema, postinflammatory pigment changes. multiple rcts 10% ala gel + red light: single or field ak on the scalp and face photosensitizer application -> incubation time of several hours -> exposure to light source. patients are educated for sun protection for several days after pdt. bf-200 ala pdt stabilize ala and increase epidermal penetration. multiple phase iii rcts europe: facial and non-facial ak united states: mild-moderate ak on face/scalp day light pdt (dl-pdt) same as conventional pdt less pain and inflammation than conventional pdt multiple rcts not available photosensitizer and sunscreen without physical https://paperpile.com/c/0idjtl/yout https://paperpile.com/c/0idjtl/3y6p https://paperpile.com/c/0idjtl/4uct https://paperpile.com/c/0idjtl/layu https://paperpile.com/c/0idjtl/rgak https://paperpile.com/c/0idjtl/eaqz https://paperpile.com/c/0idjtl/1qlk https://paperpile.com/c/0idjtl/eqzq https://paperpile.com/c/0idjtl/zx7h skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 279 blocker were applied topically>outdoor for 2 hours-> stay indoor for the rest of the day. tirbanibulin 1% ointment inhibit tubulin polymerization and upregulate p53 expression treatment site reactions, pain, pruritus two identicallydesigned, phase iii rcts ak to up 25 cm2 contiguous area of the face or scalp one packet (2.5 mg tirbanibulin in 250 mg) once /day for 5 consecutive days topical diclofenac 3% in 2.5% hyaluronic acid (dfc/ha) inhibits the cyclooxygenase-1 and cyclooxygenase-2 and decreases arachidonic acid (aa) byproduct pruritus, contact dermatitis, dry skin. milder inflammatory response than 5fu. several phase iii rcts and metaanalysis ak topically apply twice/day for 6090 days ingenol mebutate (imb) (0.015% gel and 0.05% gel) disruption of plasma membrane and mitochondria. it also triggers cytotoxic reaction pain, hypopigmentation. several phase iii rcts united states: ak 0.015% gel: once daily 3 days on face or scalp 0.05% gel: once daily for 2 days on the truck or extremities. treatment area should be less or equal to 25 cm2 identically-designed phase iii randomized clinical trials. in these trials, lsr(local skin reaction) scores were recorded from baseline to day 57.30 the lsr score composed of six components: erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration. each parameter was evaluated by a 0-3 scoring system, the sum of all parameters was calculated as the lsr score. significantly higher complete clearance (cc, 100% reduction in lesion counts at day 57) and partial clearance rate (75% reduction in lesion counts at day 57) were observed in the treatment group than placebo group. the patients who achieved cc also had a recurrence rate of 47% at 1 year follow up. the most common adverse effects were treatment site pain and pruritus, which regressed spontaneously. no one had exited the study due to any adverse event.30 nevertheless, case studies have demonstrated successful topical application of more than 25 cm2 on human skin, potentially making tirbanibulin more costeffective.31 two post-hoc analyses of the two phase iii tirbanibulin trials were reported. one compiled the lsr score from baseline to day 57 in 174 patients in the treatment group who achieved cc. 26.5% of patients (46 out of 174) had lsr ≤3 and 70.2% patients had lsr ≤5. the conclusion further supported that tirbanibulin is well tolerated by study patients.32 another one examined several factors and found ak on the face and fewer lesions at baseline were indicator for treatment success whereas fitzpatrick skin type, body-mass index (bmi), and prior ak therapies were not associated to desired clinical outcome.33 overall, the advantage of tirbanibulin is relatively short treatment course and the ease to apply the medication at home, and high patient compliance, however, the price may be a concern. 5-fluorouracil (5-fu) systemic fluorouracil has been used to cure various malignancies for decades.34 its underlying mechanism involves inhibiting https://paperpile.com/c/0idjtl/layu https://paperpile.com/c/0idjtl/layu https://paperpile.com/c/0idjtl/bf91 https://paperpile.com/c/0idjtl/yqrn https://paperpile.com/c/0idjtl/nkud https://paperpile.com/c/0idjtl/rgak skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 280 thymidylate synthetase and other key steps in dna and rna replication, as well as increasing the expression of p53.34 capecitabine is an oral prodrug converted to fluorouracil via a 3-step enzymatic process, ultimately by thymidine phosphorylase, an enzyme often overexpressed in cancerous cells. 15 high-risk solid organ transplant recipients (>2 new non-melanoma skin cancers in the past 6 months or >10 new aks in the past 12 months) received low dose oral capecitabine (1g/m2 twice daily for 14 days and off treatment for 7 days per 21 days treatment cycle). their mean incidence rate of aks was 4.77 per month before treatment and 2.32 per month during treatment.35 topical fluorouracil comes with varying doses and vehicles. the most common side effects were local inflammatory reactions, such as erythema, blistering, erosions.36 photodynamic therapy (pdt) the protocol of pdt starts with topically applying a photosensitizer, typically 5aminolevulinic acid (ala) or methyl aminolevulinate (mal) over the treatment area, proceed by an incubation period of several hours, and finally exposing to a light source. the photosensitizer has a high affinity for rapidly proliferating cells and pilosebaceous units. it acts as a prodrug and is converted to reactive oxygen species (ros) when exposing to light with appropriate wavelength (470-700 nm), finally causes cytotoxic damages.37 38 although the efficacy, safety profile, and excellent cosmetic result of pdt were demonstrated in multiple randomized clinical trials, the reported protocols were nonuniformed, with heterogeneities in length of incubation period, photosensitizer concentrations, setting of the illuminator, whether an assistive laser was used, and etc. classically, 10% ala gel and red light illuminator was approved by the fda. a split face of 40 patients with 4-8 ak lesions underwent application of either 10% or 20% ala gel followed by 1000 second blue light illumination revealed both regimens were equally effectively, but the 20% ala gel application had a more robust local inflammatory reaction.39 the most common side effects of pdt were treatment site pain, inflammation, and burning, especially after sunlight exposure. many innovative pdt approaches aimed to mitigate treatment related pain. martin documented a novel pdt intervention on the face that consisted of a 15 minutes incubation period of ala followed by 60 minutes of blue light. this novel intervention also had an equivalent efficacy with the conventional pdt with minimal pain and discomfort.40 similarly, another split face/scalp study compared conventional ala pdt protocol (incubate for 1 hour and blue light for 1000 second) versus modified protocol (blue light immediately following ala application). consequently, all patients in the modified protocol group reported significantly less pain than the control group and the efficacy were similar in both groups.41 another evolutionary modality is the daylight pdt (dl-pdt). a photosensitizer, typically ala, as well as a sunscreen without physical blocker of ultraviolet light (titanium oxide or zinc oxide) were applied topically followed by exposing the patient to sunlight for two hours. afterwards, patients are instructed to remove the excessive photosensitizer and stay indoors for the rest of the day. dl-pdt can be done anytime of the year in countries that are south to latitude 45° north, which encompasses most of europe and the united states, south america, and australia. optional outdoor temperature should be more than 10°c, otherwise, it would be too cold for the elderly patients. besides almost pain free, other advantage of dl-pdt are the https://paperpile.com/c/0idjtl/rgak https://paperpile.com/c/0idjtl/va73 https://paperpile.com/c/0idjtl/qth7 https://paperpile.com/c/0idjtl/eaqz https://paperpile.com/c/0idjtl/ra45 https://paperpile.com/c/0idjtl/jce7 https://paperpile.com/c/0idjtl/kftv https://paperpile.com/c/0idjtl/iw2c skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 281 affordability and simplicity to perform in office setting.42 several studies had proved that dlpdt are equally efficacious with conventional pdt. 43 44 one of the drawback of dl-pdt is the uncontrollability of natural weather, alternative light emitting sources, such as lamp illuminator, were also discussed to solve this problem.45 another creative modification is the nanosized emulsion integrated 7.8% ala gel, namely bf-200 ala, that stabilizes the ala molecule and augments epidermal penetration. it is marketed for ak in facial and non-facial regions in europe. conversely, it is only authorized for managing ak on the face in the united states.46 47 topical diclofenac (dfc) topical diclofenac is a non-steroidal antiinflammatory drug (nsaid), which inhibits the cyclooxygenase-1 and cyclooxygenase-2 and decreasing arachidonic acid (aa) byproduct. the aa byproduct are thought be to the culprit of tumorigenesis.48 a bilateral comparison study of dfc and 5-fu showed that dfc had a milder inflammatory reaction despite longer treatment course.49 ingenol mebutate (imb) imb incites local necrosis via disruption of the mitochondria and cellular plasma membrane. it also trigger cytotoxic reactions to specific tumor cells.50 51 it is only authorized to use in the united states, but not in european countries due to reported higher risk of nonmelanoma skin cancer (nmsc) in imb compared to imiquimod cream during the post-marketing surveillance.52 comparison of various treatment options direct comparison of distinct modalities is scarce. a prospective trial in netherlands aimed to evaluate the efficacy of four field treatments (5% 5-fu cream, 5% imiquimod cream, mal pdt, and 0.015% imb gel) for ak enrolled 624 patients who were randomly treated with either approach. at the 1-year end of treatment, the success rates were: 5fu (74.7%), imiquimod (53.9%), mal pdt (37.7%), and imb (28.9%). the treatment compliance rates were: imb (98.7%), mal pdt (96.8%), 5-fu (88.7%), and imiquimod (88.2%). good to excellent aesthetic outcome rates were: mal pdt (96.6%), imb (95.1%), 5-fu (90.3%), and imiquimod (89.7%).53 a few meta-analyses and systematic literature review have compared the relative efficacy of the existing options. the first one, published in 2012, convinced that pdt is superior to cryotherapy in terms of efficacy and cosmetic results when targeting a single lesion. additionally, dfc, 5-fu, imiquimod, and imb were equally efficacious in managing ak field.24 in 2013, gupta and colleagues ranked the following approaches from highest to lowest based on reported clearance rates: 5-fu, ala pdt (which is equivalent to imiquimod, imb, and mal pdt), cryotherapy, dfc/ hyaluronic acid, and finally placebo. conversely, other factors needs to be evaluated when judging the most suitable option for the patient.54 another metaanalysis published in 2014 examined 10 modalities and concluded that treatments with the relatively highest efficacy were: bf200 ala pdt , followed by imiquimod 5% for 16-week, ala pdt, and 5-fu 0.5%.55 a retrospective chart review scrutinized the rate of invasive scc incidences after more than 1 year of initial ak field treatment. the study emphasized that imiquimod was https://paperpile.com/c/0idjtl/lngx https://paperpile.com/c/0idjtl/n0m0 https://paperpile.com/c/0idjtl/orak https://paperpile.com/c/0idjtl/zwsr https://paperpile.com/c/0idjtl/eqzq https://paperpile.com/c/0idjtl/vspw https://paperpile.com/c/0idjtl/1qlk https://paperpile.com/c/0idjtl/w0u4 https://paperpile.com/c/0idjtl/cj49 https://paperpile.com/c/0idjtl/zx7h https://paperpile.com/c/0idjtl/s3kk https://paperpile.com/c/0idjtl/xdif https://paperpile.com/c/0idjtl/gigm https://paperpile.com/c/0idjtl/qmfc https://paperpile.com/c/0idjtl/agt0 skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 282 equivalent to 5-fu in preventing scc development; both therapeutics were superior to ala pdt. however, this study didn’t account for the treatment compliance and anatomical location. for patients who had multiple regimens for their ak, the investigators assigned them based on the first treatment they have received which may potentially neglected issues such as treatment crossover.10 a consensus was reached among several international experts in 2015 regarding clinical diagnosis and management of ak. in this consensus, patients were classified into four categories: i. 1-5 clinical ak lesions per field; ii. 6 or more ak lesions per field; iii. 6 or more ak lesions with the addition of chronic actinic damage and hyperkeratosis per field; and finally, iv. immunocompromised patients with any degree of ak severity. first, sun protection is recommended for all patients. secondly, cryotherapy is strongly recommended for single aks (category i). 0.5% 5-fu, 3.75% imiquimod, imb (0.015% gel and 0.05% gel), ala pdt, and mal pdt were strongly recommended for patients in category ii and iii. for patients in category iv, none of the approaches was highly recommended. cryotherapy, curettage, 5% 5-fu, 5% imiquimod, ala pdt, mal pdt were weakly recommended depending on case-to-case scenario.56 the most recent aad ak diagnosis and management guidelines strongly recommended sun protection, 5-fu, imiquimod, cryotherapy, and tirbanibulin, which benefits clearly outweigh the risks. remarkably, the experts firmly believed that the actual therapeutic effect of tirbanibulin was close to the reported therapeutic effect. other options, dfc, ala red light pdt, ala blue light pdt, dl pdt should be employed in certain conditions as the benefits finely balance with risks.57 the limitations of the available clinical evidence were the meager of long-term follow up data and effective armamentarium for immunocompromised patients and nonfacial ak. we necessitate more research in those aspects to further assist our management and comprehension of ak, and even scc. actinic keratosis usually occurs at sunexposed areas. although the risk for individual ak progressing into scc is low, the majority of scc arise from ak. its pathogenesis involves the uv-b induced thymine dimer formation, mutation of tumor suppressor genes, disruption of cell cycle, and finally, the proliferation of neoplastic keratinocytes. treatment of ak can be categorized by single lesion or field treatment. the theory of field cancerization suggests that skin tissue proximal ak lesions also have a higher risk of progression, thus, field treatments are more commonly used. sun protection is crucial for all patients. liquid nitrogen cryotherapy is the mainstay treatment for single ak, while pdt, topical imiquimod, and fluorouracil are commonly used as field treatment. tirbanibulin, recently approved by the fda, was endorsed as a highly effective option per consensus guidelines. ultimately, more studies concerning long term recurrence rate, suitable approaches for immunocompromised patients and non-facial ak are mandated. concensus guidelines limitations conclusion https://paperpile.com/c/0idjtl/660w https://paperpile.com/c/0idjtl/wgjr https://paperpile.com/c/0idjtl/62v9 skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 283 conflict of interest disclosures: hh & dkb: none bb: biofrontera, advisory board & investigator; sun pharmaceuticals, inc advisory board & consultant; leo pharma, us speaker, advisory board & investigator; almirall llc, consultant, speaker; phd biosciences, consultant funding: none corresponding author: brian berman, md, phd center for clinical and cosmetic research 2925 aventura boulevard, suite 205 aventura, fl 33180 email: bbmdphd@gmail.com references: 1. reinehr cph, bakos rm. actinic keratoses: review of clinical, dermoscopic, and therapeutic aspects. an bras dermatol. 2019;94(6):637-657. 2. schmitt jv, miot ha. actinic keratosis: a clinical and epidemiological revision. an bras dermatol. 2012;87(3):425-434. 3. cockerell cj. histopathology of incipient intraepidermal squamous cell carcinoma (“actinic keratosis”). j am acad dermatol. 2000;42(1, part 2):s11-s17. 4. marques e, chen tm. actinic keratosis. in: statpearls. statpearls publishing; 2022. 5. yaldiz m. prevalence of actinic keratosis in patients attending the dermatology outpatient clinic. medicine . 2019;98(28):e16465. 6. 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keratosis. n engl j med. 2019;380(10):935-946. 54. gupta ak, paquet m. network meta-analysis of the outcome “participant complete clearance” in nonimmunosuppressed participants of eight interventions for actinic keratosis: a follow-up on a cochrane review. br j dermatol. 2013;169(2):250-259. 55. vegter s, tolley k. a network meta-analysis of the relative efficacy of treatments for actinic keratosis of the face or scalp in europe. plos one. 2014;9(6):e96829. 56. werner rn, stockfleth e, connolly sm, et al. evidenceand consensus-based (s3) guidelines for the treatment of actinic keratosis international league of dermatological societies in cooperation with the european dermatology forum short version. journal of the european academy of dermatology and venereology. 2015;29(11):2069-2079. doi:10.1111/jdv.13180 57. eisen db, dellavalle rp, frazer-green l, schlesinger te, shive m, wu pa. focused update to the guidelines of care for the management of actinic keratosis: executive summary. j am acad dermatol. published online april 16, 2022. doi:10.1016/j.jaad.2022.04.013 http://paperpile.com/b/0idjtl/zwsr http://paperpile.com/b/0idjtl/zwsr http://paperpile.com/b/0idjtl/zwsr http://paperpile.com/b/0idjtl/zwsr http://paperpile.com/b/0idjtl/eqzq http://paperpile.com/b/0idjtl/eqzq http://paperpile.com/b/0idjtl/eqzq http://paperpile.com/b/0idjtl/eqzq http://paperpile.com/b/0idjtl/eqzq http://paperpile.com/b/0idjtl/eqzq http://paperpile.com/b/0idjtl/eqzq http://paperpile.com/b/0idjtl/eqzq http://paperpile.com/b/0idjtl/eqzq http://paperpile.com/b/0idjtl/vspw http://paperpile.com/b/0idjtl/vspw http://paperpile.com/b/0idjtl/vspw http://paperpile.com/b/0idjtl/vspw http://paperpile.com/b/0idjtl/vspw http://paperpile.com/b/0idjtl/vspw http://paperpile.com/b/0idjtl/vspw http://paperpile.com/b/0idjtl/vspw http://paperpile.com/b/0idjtl/vspw http://paperpile.com/b/0idjtl/vspw http://paperpile.com/b/0idjtl/vspw http://paperpile.com/b/0idjtl/1qlk http://paperpile.com/b/0idjtl/1qlk 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almost clear plus ≥2-grade improvement from baseline. b-iga: body-investigator global assessment; bsa: body surface area; dlqi: dermatology life quality index; iga: investigator global assessment; nrs: numeric rating scale; pasi: psoriasis area severity index; psd: psoriasis symptom diary; pssi: psoriasis scalp severity index; qd: once daily; s-iga: scalp-investigator global assessment; si-nrs: scalp itch-numeric rating scale; wi-nrs: worst itch-numeric rating scale. figure 1. study design once-daily roflumilast foam 0.3% improves severity and burden of itch in patients with scalp and body psoriasis in a randomized, double-blind, vehicle-controlled phase 2b study angela y. moore,1 javier alonso-llamazares,2 neal bhatia,3 michael bukhalo,4 alim r. devani,5 zoe d. draelos,6 melinda j. gooderham,7 steven e. kempers,8 leon h. kircik,9 kim a. papp,10 david m. pariser,11 marina sankeva,12 rodney sinclair,13 matthew zirwas,14 amy feng,15 patrick burnett,15 robert higham,15 david berk15 1arlington center for dermatology, arlington research center, arlington, tx and baylor university medical center, dallas, tx, usa; 2driven research llc, coral gables, fl, usa; 3therapeutics clinical research, san diego, ca, usa; 4arlington dermatology, rolling meadows, il, usa; 5dermatology research institute and probity medical research, calgary, ab, canada; 6dermatology consulting services, high point, nc, usa; 7skin centre for dermatology, probity medical research and queen’s university, peterborough, on, canada; 8minnesota clinical study center, fridley, mn, usa; 9icahn school of medicine at mount sinai, ny, indiana medical center, indianapolis, in, physicians skin care, pllc, louisville, ky, and skin sciences, pllc, louisville, ky, usa; 10probity medical research and k papp clinical research, waterloo, on, canada; 11eastern virginia medical school and virginia clinical research, inc., norfolk, va, usa; 12private practice, gabrovo, bulgaria; 13sinclair dermatology, east melbourne, victoria, australia; 14dermatologists of the central states, probity medical research, and ohio university, bexley, oh, usa; 15arcutis biotherapeutics, inc., westlake village, ca, usa introduction • in patients with psoriasis, about 80% have scalp psoriasis1 – scalp psoriasis is often associated with itch, the most burdensome symptom of psoriasis2 – itching, flaking, and plaque visibility on the scalp can cause social embarrassment and adversely impact quality of life3 – treatment of scalp psoriasis is difficult because the hair may limit efficacy of creams and ointments and reduce treatment adherence4 • roflumilast is a selective and highly potent phosphodiesterase-4 inhibitor being investigated as a once-daily, nonsteroidal, topical treatment for various dermatologic conditions – roflumilast foam is uniquely formulated as an emollient, water-based, moisturizing foam that can be used on the scalp or body – roflumilast cream met the primary and secondary endpoints and was welltolerated in a phase 2b, randomized, double-blind, vehicle-controlled trial in adults with psoriasis5 • we investigated roflumilast foam for scalp and body psoriasis in a phase 2b, randomized, double-blind, vehicle-controlled 8-week study (clinicaltrials.gov identifier: nct04128007) methods • this was a parallel-group, double-blind, vehicle-controlled clinical trial (figure 1) • eligible patients were adults and adolescents ≥12 years old with diagnoses of scalp and body psoriasis for at least 6 months • patients were randomized 2:1 to roflumilast 0.3% or matching vehicle foam • the primary efficacy endpoint was scalp-investigator global assessment (s-iga) success, defined as achievement of an s-iga score of clear or almost clear plus a 2-grade improvement from baseline at week 8 • efficacy endpoints were analyzed using a cochran-mantel-haenszel test stratified by country, baseline s-iga, and baseline body-iga (b-iga) category using multiple imputation for missing data – statistical tests were conducted at the 5% significance level using 2-tailed tests endpoints primary • s-iga success secondary • b-iga success • si-nrs • wi-nrs • psd • dlqi safety and tolerability 8 weeks dosing visits: weeks 2, 4, 8, plus 1 week post-treatment eligibility • aged ≥12 years • diagnosis of scalp and body plaque psoriasis • at least mild severitya on both s-iga and b-iga • ≤25% bsa • pssi ≥6 • ≥10% of scalp involved • pasi ≥2 roflumilast foam 0.3% qd (n=200) vehicle qd (n=104) ra nd om iz e 2:1 n=304 • 96% power at α=0.05 to detect 22.4% difference between groups for s-iga success, based on 201 results showing 32.2% vs 9.8% iga success at week 85 results • a total of 304 patients were randomized to roflumilast foam 0.3% (n=200) or vehicle foam (n=104; intent-to-treat [itt] population; table 1) – of these, 198 patients in the roflumilast group (99%) and 104 in the vehicle group (100%) received ≥1 confirmed dose of their study intervention (safety population) • most patients (83.7% to 88.5%) completed the study (table 1) • baseline disease characteristics were balanced across treatment groups (table 2) conclusions • patients with scalp psoriasis need topical treatments that provide effective control of psoriasis with low incidence of side effects • in this phase 2b study, once-daily roflumilast foam significantly improved both scalp and body psoriasis, apparent as early as 2 weeks after treatment initiation – scalp and body itch abated by week 2 with further reduction throughout the study • roflumilast foam was well-tolerated with low rates of treatment-emergent aes, application-site aes, and discontinuations due to ae – rates of these events were similar to vehicle • favorable safety profile and encouraging efficacy results warrant further investigation of once-daily roflumilast foam as a potential novel therapy for the treatment of scalp and body psoriasis disclosures aym, ja-l, nb, mb, ard, zdd, mjg, sek, lhk, kap, dmp, ms, rs, and mz are investigators and/or consultants for arcutis biotherapeutics, inc. and received grants/research funding and/ or honoraria; af, pb, rch, and drb are employees of arcutis biotherapeutics, inc. additional disclosures provided on request. safety • rates of treatment-emergent aes and discontinuation due to aes were low (table 3) • treatment-related aes were uncommon • only 1 patient had a serious ae (unrelated) • very few aes led to study discontinuation – discontinuation rates were similar between groups • ≥99% of roflumilastand ≥98% of vehicle-treated patients had no evidence of irritation on the investigator rating of local tolerability table 3. adverse events teaes, n (%) roflumilast foam 0.3% (n=198) vehicle foam (n=104) patients with any teae 46 (23.2) 20 (19.2) patients with any treatment-related teae 8 (4.0) 9 (8.7) patients with any serious aea 1 (0.5) 0 patients who discontinued study due to aeb 5 (2.5) 2 (1.9) most common teae (>1.5% in any group), preferred term application-site pain 2 (1.0) 4 (3.8) covid-19 3 (1.5) 2 (1.9) psoriasis 1 (0.5) 2 (1.9) sinusitis 1 (0.5) 2 (1.9) hypertension 3 (1.5) 1 (1.0) diarrhea 3 (1.5) 0 aserious ae: testicular torsion, unrelated. bae leading to discontinuation: roflumilast: application-site pruritus, abdominal discomfort, diarrhea, headache, application-site pain, application-site discoloration, application-site irritation, lethargy; vehicle arm: psoriasis, application-site dermatitis. ae: adverse event; teae: treatment-emergent adverse event. figure 2. percentages of patients achieving s-iga success (a) and b-iga success (b) aintent-to-treat population. b-iga: body-investigator global assessment; ci: confidence interval; s-iga: scalp-investigator global assessment. 9.5% 21.3% 40.3% 1.0% 5.6% 6.8% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% week 2 week 4 week 8 % o f p at ie nt s (9 5% c i) roflumilast foam 0.3% (n=200) vehicle foam (n=104) p=0.0079 p<0.0001 p=0.0011 26.0% of patients on roflumilast achieved b-iga status of clear versus 3.4% on vehicle 100 90 80 70 60 50 40 30 20 10 0 17.4% 41.3% 59.1% 3.1% 5.6% 11.4% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% week 2 week 4 week 8 % o f p at ie nt s (9 5% c i) roflumilast foam 0.3% (n=200) vehicle foam (n=104) p=0.0007 p<0.0001 p<0.0001 34.3% of patients on roflumilast achieved s-iga status of clear versus 3.4% on vehicle 100 90 80 70 60 50 40 30 20 10 0 s-iga success = clear or almost clear plus ≥2-grade improvement from baselinea b-iga success = clear or almost clear plus ≥2-grade improvement from baselinea (a) (b) figure 3. percentages of patients achieving si-nrs 4-point response (a) and wi-nrs 4-point response (b) to control for multiple comparisons among the secondary endpoints, a multiplicity procedure was used. upon successful testing of the primary endpoint, the α was partitioned to test secondary endpoints. aevaluated in patients with si-nrs score ≥4 at baseline; bevaluated in patients with wi-nrs score ≥4 at baseline. ci: confidence interval; si-nrs: scalp itch-numeric rating scale; wi-nrs: worst itch-numeric rating scale. figure 4. psd item 1 (severity of itch; a) and item 2 (burden of itch; b) table 1. patient disposition n (%) roflumilast foam 0.3% (n=200) vehicle foam (n=104) completed 177 (88.5) 87 (83.7) prematurely discontinued 23 (11.5) 17 (16.3) reason for discontinuation withdrawal by subject 9 (4.5) 6 (5.8) noncompliance 1 (0.5) 0 protocol violation 0 0 lost to follow-up 8 (4.0) 7 (6.7) adverse event 5 (2.5) 2 (1.9) other 0 2 (1.9) table 2. baseline disease characteristics (itt population) n (%) roflumilast foam 0.3% (n=200)a vehicle foam (n=104) bsa, mean % 8.0 7.6 baseline s-iga 2 – mild 18 (9.0) 14 (13.5) 3 – moderate 151 (75.5) 80 (76.9) 4 – severe 29 (14.5) 10 (9.6) baseline b-iga 2 – mild 69 (34.5) 39 (37.5) 3 – moderate 119 (59.5) 60 (57.7) 4 – severe 10 (5.0) 5 (4.8) pssi, mean (sd) 22.4 (12.5) 20.9 (11.7) pasi, mean (sd) 7.2 (4.3) 6.8 (4.4) si-nrs, mean (sd) 6.4 (2.4) 6.6 (2.3) si-nrs, ≥4, n (%) 173 (86.5) 96 (92.3) wi-nrs, mean (sd) 6.4 (2.48) 6.7 (2.32) wi-nrs ≥4, n (%) 165 (82.5) 94 (90.4) psd total score mean (sd) 78.5 (39.92) 84.3 (38.76) psd item 1: severity of itch, mean (sd) 6.3 (2.54) 6.7 (2.07) psd item 2: burden of itch, mean (sd) 6.1 (2.73) 6.5 (2.50) dlqi, mean (sd) 6.6 (5.18) 6.8 (4.66) atwo patients were missing baseline values due to capture outside of the date-time visit window and were not evaluable. b-iga: body-investigator global assessment; bsa: body surface area; dlqi: dermatology life quality index; itt: intent-to-treat; pasi: psoriasis area severity index; psd: psoriasis symptom diary; pssi: psoriasis scalp severity index; sd: standard deviation; s-iga: scalp-investigator global assessment; si-nrs: scalp itch-numeric rating scale; wi-nrs: worst itch-numeric rating scale. • rates of discontinuation due to adverse event (ae) were low efficacy • roflumilast foam significantly improved scalp and body psoriasis at all timepoints (figure 2) • roflumilast significantly improved scalp and body itch by week 2 and consistently improved itch through week 8 (figure 3) • roflumilast foam significantly improved patient-reported severity and burden of itch as indicated by improvements on the psoriasis symptom diary (psd) items 1 (severity of itch) and 2 (burden of itch; figure 4) • roflumilast-treated patients also had a significant improvement in quality of life as indicated by the dermatology life quality index (dlqi; figure 5) 44.6% 62.0% 71.0% 15.6% 22.1% 18.5% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% week 2 week 4 week 8 pa tie nt s (% ) roflumilast foam 0.3% (n=173) vehicle foam (n=96) p<0.0001 p<0.0001 p<0.0001 100 90 80 70 60 50 40 30 20 10 0 % o f p at ie nt s (9 5% c i) 45.3% 57% 68.2% 11.5% 20.5% 23.1% 0% 1000% 2000% 3000% 4000% 5000% 6000% 7000% 8000% 9000% 10000% week 2 week 4 week 8 % o f p at ie nt s (9 5% c i) roflumilast foam 0.3% (n=165) vehicle (n=94) p<0.0001 p<0.0001 p<0.0001 100 90 80 70 60 50 40 30 20 10 0 >70% of patients achieved a si-nrs 4-point response at week 8 (a) (b) more than two-thirds of patients had a ≥4-point improvement on wi-nrs at week 8 wi-nrs 4-point responsebsi-nrs 4-point responsea figure 5. ls mean change from baseline in dlqi estimates from an ancova model with country, treatment, baseline s-iga score category, baseline b-iga score category, and baseline dlqi score as independent variables. intent-to-treat population. ancova: analysis of covariance; b-iga: body-investigator global assessment; cfb: change from baseline; dlqi: dermatology life quality index; ls: least squares; qol: quality of life; se: standard error; s-iga: scalp-investigator global assessment. 0.0% -27.8% -47.3% -61.6% 0.0% 17.0% -2.5% -17.7% baseline week 2 week 4 week 8 0 −20 −40 −60 −80 −120 −100 ls m ea n % c fb (s e) 20 40 overall qol benefit was higher with roflumilast than with vehicle roflumilast foam 0.3% (n=200) vehicle foam (n=104) p<0.0001 p<0.0001 p<0.0001 0.0% -42.3% -50.4% -60.6% -16.2% -26.1% -27.0% -100% -80% -60% -40% -20% 0% baseline week 2 week 4 week 8 m ea n % c fb (9 5% c i) roflumilast foam 0.3% (n=200) vehicle foam (n=104) 0.0% -39.9% -49.5% -59.6% -18.5% -24.5% -26.5% -100% -80% -60% -40% -20% 0% baseline week 2 week 4 week 8 m ea n % c fb (9 5% c i) roflumilast foam 0.3% (n=200) vehicle foam (n=104) roflumilast treatment resulted in greater reduction in severity of itch (a) (b) burden of itch was reduced to a greater extent with roflumilast psd item 1 (severity of itch)a how severe was your psoriasis-related itching over the past 24 hours? psd item 2 (burden of itch)a how bothered were you by your psoriasis-related itching over the past 24 hours? 0 −20 −40 −60 −80 −100 0 −20 −40 −60 −80 −100 to control for multiple comparisons among the secondary endpoints, a multiplicity procedure was used. upon successful testing of the primary endpoint, the α was partitioned to test secondary endpoints. estimates from an ancova model with country, treatment, baseline s-iga score category, baseline b-iga score category, and baseline psd score as independent variables. intent-to-treat population. ancova: analysis of covariance; b-iga: body-investigator global assessment; cfb: change from baseline; ci: confidence interval; psd: psoriasis symptom diary; se: standard error; s-iga: scalp-investigator global assessment. references 1. chan cs, et al. j am acad dermatol 2009;60:962-971. 2. elewski b, et al. j eur acad dermatol venereol 2019;33:1465-1476. 3. dopytalska k, et al. reumatologia 2018;56:392-398. 4. blakely k, gooderham m. psoriasis 2016;6:33-40. 5. lebwohl mg, et al. n engl j med 2020;383:229-239. acknowledgements • this study was supported by arcutis biotherapeutics, inc. • thank you to the investigators and their staff for their participation in the trial • we are grateful to the study participants and their families for their time and commitment • writing support was provided by christina mcmanus, phd, alligent biopharm consulting llc, and funded by arcutis 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/mainmonitorcolors /useembeddedprofiles false /usehtmltitleasmetadata true >> ] >> setdistillerparams << /hwresolution [2400 2400] /pagesize [612.000 792.000] >> setpagedevice skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 374 original research thermal burn wounds produce greater scars compared to similarly sized excisional wounds and topical amiloride applied to burn-induced scars shows scar reduction adrian e. rodrigues, md*1, david dolivo, phd*1, yingxing li, bs1, chun hou, md1,2, lauren sun, ba1, thomas a. mustoe, md1, seok jong hong, phd1, and robert d. galiano, md1 *these authors contributed equally to this work 1 department of surgery, division of plastic surgery, northwestern university, feinberg school of medicine, chicago, il 2 department of plastic and cosmetic surgery, first affiliated hospital of guangzhou medical university, guangzhou, china traumatic skin injuries such as large lacerations and severe thermal burns commonly conclude with pathological scars.1,2 skin sequela such as hypertrophic scars, keloids and contractures frequently form after skin re-epithelialization, with all three manifestations harboring abundant abstract background: victims of severe traumatic injuries such as large surface area lacerations and thermal burns require substantial medical care that primarily promotes healing. and although this care is essential, there is a lack of pharmacological treatments that reduce the resulting scars, consequently leaving many traumatic victims with profusely disfigured skin. methods: a rabbit-ear injury model was used to compare scar progression in adjacently paired contact thermal burns (n=24) and excisional wounds (n=16). once that model revealed significant differences in scar hypertrophy between these two types of injuries, a succeeding study involved solely inducing burns, with the resulting wounds undergoing scar elevation index (sei) and gene expression analysis after unilateral topical treatment with either amiloride (n=12), celecoxib (n=11) or contralateral vehicle control (n=10 for each of the two control groups). results: in the initial burn and excisional wound comparison study, thermal burns showed significantly larger scars, both in scar height measured at four timepoints (p<0.0001, <0.01, <0.05, and <0.05) and histologically by analyzing the sei (p<0.05). in the succeeding project, burn-induced scars treated with amiloride also demonstrated a significantly reduced histological sei (p<0.05) compared to scars receiving vehicle control. however, relative ptgs2, acta2 and col1a1 expression was not significantly different in scar tissues treated with amiloride compared to those receiving vehicle control. also, no significant differences in sei were determined in scars treated with celecoxib compared to vehicle control conclusions: contact thermal burn injuries create profusive hypertrophic scars compared to similarly sized excisional wounds. topical application of amiloride to burn-induced scars reduce scar formation, yet this finding necessitates further studies to comprehend the mechanism behind its scarreducing effect. introduction skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 375 fibrotic extracellular matrix deposition,3,4 and often times accompanied with pain, pruritus, paresthesia, limited mobility and/or psychosocial distress.5-7 although various skin injuries — chemical, electrical, scald, abrasions and lacerations — have the potential to heal with pathological scars, some research has found that contact thermal burn injuries heal with more substantial scars when compared to similarly sized excisional wounds.8-10 with such findings, and having a scar reduction study to pursue, we opted to first test whether considerable differences in scar development materialize between two similarly sized adjacent injuries: contact thermal burns and excisional wounds. the objective being that data from this study would help us select a significant scarproducing injury, and that such selected injury would be well-matched for a secondary project aimed at testing the scarreducing potential of amiloride and celecoxib. this was the basis of these two experiments. however, the principle behind the potential for these drugs to minimize scar development arose from previously published in vitro work involving amiloride and fibroblasts. amiloride, a widely used drug to treat hypertension, heart failure and, in some instances, treat or prevent hypokalemia, functions through selective inhibition of epithelial sodium channels (enac), na+/h+ exchangers and na+/ca2+ exchangers in kidney tubules, effectively reducing intracellular sodium and enhancing the tubule diuretic effect.11 although mainly recognized as a nephron-targeting drug, amiloride has also shown activity outside of the kidney. in a former study, in vitro induction of enac-mediated sodium flux by reduced hydration activated fibroblasts through the cyclooxygenase-2/prostaglandin e2 (cox-2/pge2) pathway, successively promoting collagen deposition from human dermal fibroblasts.12 however, amilorideinduced inhibition of enac in keratinocytes prevented fibroblasts from generating collagen deposition, thereby demonstrating that enac promotes fibroblast activation via enac-dependent paracrine signaling in response to reduced hydration. given that skin injuries disrupt the integumentary barrier and consequently produce local dehydration by increasing transepidermal water loss (tewl),13 and since burn scars also exhibit increased tewl compared to normal skin,14 we hypothesized that amiloride (and celecoxib due to its cox-2 antagonistic effect) could reduce scar formation in an in vivo study by hampering collagen production in a rabbit-ear injury model. this study complied with national research council's guide for the care and use of laboratory animals and was approved by the institutional animal care and use committee. the project utilized new zealand white female rabbits (envigo, indianapolis, in) aged 17-22 weeks and weighing 2.7-3.2 kilograms at the start of the study. during discomforting procedures, animals were placed under an anesthetic plane (ketamine 40 mg/kg, xylazine 5 mg/kg) and received systemic (buprenorphine sr 0.2 mg/kg) and local (lidocaine 4 mg/kg, except during burn induction) pain control along with core body temperature assistance. the use of ecollars was also used to safeguard wounds. wounding process: excisional injuries surgical excisional wounds were performed on the ventral surface of ears using a 7 mmmethods skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 376 diameter biopsy punch, whereby a circular skin incision was made until the depth was tangential to the underlying perichondrium. once a circular incised border was visible, forceps were used to grasp the incised tissue and traction was applied to bluntly free the skin and complete the excision. tegaderm film dressing (3m, maplewood, mn) was immediately applied over the excised wounds and remained until complete re-epithelialization, with scartissue harvesting taking place upon conclusion of the study. wounding process: contact thermal burns burns were performed with a 1-cm diameter cylindrical 90-gram brass rod, heated within an isotemptm dry block and heater (fisher scientific, pittsburg, pa). once the temperature on the heater stabilized, the rod was removed from the dry block and placed on an ambient temperature k-type tl0225 thermocouple (perfect prime, far rockaway, ny) so that real-time temperature readings could be displayed on a digi-sense 20250-08 thermometer (coleparmer, vernon hills, il). once the temperature declined to 94° c, the rod was immediately transferred to the ventral ear for an 8 second freestanding burn induction. five days later, debridement of burninduced eschar buildup was performed tangential to the underlying perichondrium with a 7 mm-diameter biopsy punch and forceps. tegaderm film dressing was then applied over the debrided wounds and remained until complete re-epithelialization, with scar-tissue harvesting taking place upon conclusion of the study. scar comparison of burn and excisional wounds eight rabbits (one ear from each animal) were used to compare scar formation from paired burn and excisional injuries that progressed free from pharmacological intervention. on post-operation day (pod) 0, burns (n=24) were introduced with eschar debridement occurring on pod 5. on this same day, soon after debridement, excisional wounds (n=16) were made adjacent to burn-induced wounds. as healing progressed, scar height was measured in both types of injuries on pod 12, 21, 26 and 28 with calipers by directly contacting the scar (ventral surface) and the normal skin directly underneath the scar (dorsal surface). on pod 29 the scar tissues were harvested for scar elevation index (sei) analysis. pharmacological application to burninduced scars skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 377 figure 2. timeline and data from study comparing scars from paired burn and excisional wounds. a) timeline of study undergoing both burns and excisional wounds, with top values indicating post-operation day (pod) and bottom content relating to events. b) bar graphs illustrating data from the four days caliper scar measurements were obtained. c) bar graph comparing the histological scar elevation index (sei) between burns and excisions at pod 29. bar graphs represent mean ± standard deviation. figure 1. method used for calculating the scar elevation index (sei). sketch of the dorsal and ventral skin layers found in the rabbit ear, portrayed with a developing hypertrophic scar (hypertrophic neodermis). the sei is calculated with histological images, whereby the area of the ventral dermis (stars) within the wound margins is summed with the area of the hypertrophic neodermis (moons), and subsequently divided by the area of ventral dermis (stars). skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 378 eight rabbits divided into two groups (4 allocated to receive amiloride to one ear and vehicle control to the contralateral ear, and 4 allocated receive celecoxib to one ear and vehicle control to the contralateral ear) were used to test the scar-reducing capabilities of selected drugs and vehicle controls. animals underwent burns to both ears with subsequent eschar debridement. under each group tested, scars from a unilateral ear underwent topical treatment (amiloride n=12, or celecoxib n=11) while scars on the contralateral ear underwent vehicle control application (n=10 for each of the two control groups). treatments and vehicle controls were applied five times over the course of ten days (pod 18, 20, 22, 25, 27) with scar tissue harvested on pod 29. drug preparation, histology, and qpcr gene expression amiloride (sigma-aldrich, st. louis, mo) and celecoxib (sigma-aldrich) were used to treat the developing scars. to increase penetration of these drugs through skin, each was dissolved in a microemulsion vehicle consisting of transcutol (as a surfactant) and capmul mcm (as an emulsifier) at a ratio of 1:1 (v:v).15,16 dissolved drugs, 2% amiloride and 4% celecoxib, were then mixed with vaseline lotion (unilever, trumbull, ct) in a ratio of 1:2 (v:v), and placed inside syringes for subsequent application of roughly 20 μl onto each scar of either drug or vehicle control. on day 29, scar tissues from burns and excisions were harvested, fixed in 10% neutral-buffered formalin, and subsequently dehydrated in serial ethanol and embedded in paraffin for microtome sectioning. sectioned samples (5 μm-thick) were stained with hematoxylin and eosin (h&e) according to standard protocols, and histological images and measurements were captured using a nikon eclipse 50i (nikon instruments, melville, ny). using these image captures, the scar elevation index (sei) was determined by adding the area within the ventral dermis wound margins and hypertrophic neodermis and dividing by the area of the ventral dermis (figure 1). rna isolation was conducted from whole tissue scars for real-time pcr analyses with primers specific to rabbit type i collagen (col1a1), alpha-smooth muscle actin (acta2), cyclooxygenase-2 (ptgs2) and gapdh as a reference control. to test for significant differences between groups, mean values were compared with two-tailed unpaired student’s t-tests on data from wound height caliper measurements, histological sei values and qpcr expression markers. graphical data are expressed as the mean ± standard deviation, n = number of wounds. differences were considered significant when p values were < 0.05 (*), <0.01 (**), <0.001 (***), <0.0001(****) and not significant (ns) when p values were > 0.05. statistical analysis was performed with graphpad prism 9 (graphpad, san diego, ca). scar comparison of burn and excisional wounds scar comparison among paired burn and excisional-induced injuries revealed that burn wounds produce scars with greater height when compared to equally sized excision-induced scars measured at the same time point. among the four timepoints measured with calipers, pod 12 showed the greatest difference (p <0.0001), with the final two days, pod 26 and 28, showing consecutively thicker scars (p <0.05 for both days) among burn-induced wounds (figure 2, a and b). moreover, the sei calculated results skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 379 from these scar tissues also complemented the caliper measurements, revealing that burn-induced scars are significantly more elevated (p <0.05) than excisional-induced scars (figure 2c). these quantitative findings were also consistent with gross observations, whereby the appearance of burn-induced scars was visibly more exacerbated than excisional-induced scars (figure 3). figure 3. gross image of a rabbit ear with two excisional-induced scars (contain the letter “e”) and three hypertrophic burn-induced scars (contain the letter “b”) on pod 29. pharmacological application to burninduced scars burn-induced wounds under the amiloride group of animals showed that scars treated with topical amiloride were characterized by a significantly reduced sei (p <0.05) compared to the contralateral scars allocated to vehicle control (figure 4, a and b); with representative histological images of both treatment and vehicle control supportive of this finding (figure 5, a and b). gene expression analysis for ptgs2, acta2 and col1a1 was performed by qrt-pcr on whole-scar tissues that underwent amiloride and vehicle application, but significant gene expression differences could not be determined in this group (figure 6, a-c). under the group of animals allocated to test celecoxib and vehicle control, only a small decline in the sei emerged under scars treated with celecoxib, with the fall being statistically insignificant (figure 4c). the histological images also complemented the sei results, showing only a minor visibly evident reduction. (figure 5, c and d). given the negative results with celecoxib, tissue gene expression analysis was not performed in this group. after pairing both burn and excisional wounds onto individual ears, we found our data supportive of previously reported results. encouraging as this was, even more worthwhile was that there was a selectable superior injury that reliably materialized reproducible scars: one with worsened, more exacerbated scars, therefore making it remarkably suited for a scar reduction study. discussion skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 380 figure 5. histological images of scars harvested on post-operation day 29. a) unilateral scar that underwent vehicle control application, and b) its corresponding contralateral amiloride treated scar, showing an enlarged epidermis yet overall reduced scar. c) unilateral scar that underwent vehicle control application, and d) its corresponding contralateral celecoxib treated scar, also showing an enlarged epidermis with an overall minor scar reduction. figure 4. timeline and data from study pharmacologically treating burn-induced scars. a) timeline of study undergoing pharmacological treatment of burn-induced scars, with top numerical values indicating post-operation day (pod) and bottom content relating to events and treatments. b) bar graph illustrating a significantly reduced sei in burn scars treated with amiloride compared to vehicle control, and c) no significant difference in sei in scars treated with celecoxib when compared to vehicle control scars. bar graphs represent mean ± standard deviation. skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 381 since we now had a consistent model that demonstrated hypertrophic scars with burns, we opted to test whether such scars could be reduced with amiloride or celecoxib. upon conclusion, celecoxib-treated scars were insignificantly reduced. however, the data did reveal a significant sei reduction with amiloride, yet complementing this finding with a downregulated expression of cox-2 (ptgs2) — a finding that holds importance in previous wound studies including those analyzing scars12,17,18, and a mechanistic step by which in vitro work revealed collagen hinderance12— was not possible in this study. similarly, myofibroblast cells — which correlate with alpha smooth muscle actin (acta2) expression and are well-known contributors of collagen deposition — were also insignificantly present in these tissues. and lastly, type i collagen (col1a1), a protein found in abundance within mature scars, was also not differentially expressed between amiloride-treated and vehicle control scars. given the unsupportive gene expression data, we cannot comment with any certainty on amiloride’s mechanistic scar reduction pathway. we can only speculate that antagonizing enac likely cascades a unique scar reduction mechanism, and that such mechanism may be at least partially independent of cox-2. clearly, in vivo burnscar production, and in our case reduction, is complex. so much so, that other researchers who have analyzed bulk gene transcription in hypertrophic burn scars have reported a large number of genes that are either down or up regulated,19 while other studies have reported distinctive, yet complex, inflammatory responses in scar tissues.8,10,20 still, regardless of their complexities, such injuries warrant further studies. although the wound healing phases along with key cellular and protein signaling are wellunderstood in some injury modalities,21 the full mechanisms by which pathological scars arise is relatively obscure. while tension and infection are well-known hypertrophic scar contributors, keloids and contractures remain the most elusive because they are relatively human traits (particularly keloids).22 for now, the best treatments for some type of scars involves an invasive approach, such as cryosurgery or carbon dioxide laser ablation.23,24 future studies however, should aim to couple both invasive and pharmacological approaches to assess the best outcome, and to better understand subsets of scar-forming wounds that preferentially respond to various treatment modalities, including biomarkers that may be used to distinguish tested subsets. skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 382 figure 6. qrt-pcr gene expression analysis comparing scars that underwent amiloride and vehicle control application. a) no significance in ptgs2 (cyclooxygenase-2) quantification relative to gapdh in whole skin scar samples between vehicle and amiloride-treated wounds. b) no significance in acta2 (α-smooth muscle actin) quantification in whole skin scar samples between vehicle and amiloride-treated wounds. c) no significance in col1a1 (type i collagen) quantification in whole skin scar samples between vehicle and amiloride-treated wounds. bar graphs represent mean ± standard deviation. conflict of interest disclosures: none funding: this article was funded by the united states army medical research acquisition activity, grant #w81xwh1920038, awarded to robert galiano md corresponding author: robert d. galiano, md northwestern university feinberg school of medicine division of plastic surgery 675 n. st. clair st., suite 19-250 chicago, il 60611 phone: 312-695-6022 fax: 312-695-5672 email: robert.galiano@nm.org references: 1. smolle c, cambiaso-daniel j, forbes aa, et al. recent trends in burn epidemiology worldwide: a systematic review. burns. mar 2017;43(2):249-257. 2. kraemer md, jones t, deitch ea. burn contractures: incidence, predisposing factors, and results of surgical therapy. j burn care rehabil. may-jun 1988;9(3):261-265. 3. reinke jm, sorg h. wound repair and regeneration. european surgical research. 2012;49(1):35-43. 4. nedelec b, shankowsky h, scott pg, ghahary a, tredget ee. myofibroblasts and apoptosis in human hypertrophic scars: the effect of interferon-alpha2b. surgery. nov 2001;130(5):798-808. 5. eishi k, bae sj, ogawa f, hamasaki y, shimizu k, katayama i. silicone gel sheets relieve pain and pruritus with clinical improvement of keloid: possible target of mast cells. j dermatolog treat. dec 2003;14(4):248-252. 6. xiao y, sun y, zhu b, et al. risk factors for hypertrophic burn scar pain, pruritus, and paresthesia development. wound repair regen. mar 2018;26(2):172-181. 7. van loey ne, van son mj. psychopathology and psychological problems in patients with burn scars: epidemiology and management. am j clin dermatol. 2003;4(4):245-272. 8. rodrigues ae, dolivo d, li y, mustoe ta, galiano rd, hong sj. comparison of thermal burn-induced and excisional-induced scarring in animal models: a review of the literature. adv wound care (new rochelle). nov 27 2021. 9. friedrich ee, niknam-bienia s, xie p, et al. thermal injury model in the rabbit ear with quantifiable burn progression and hypertrophic scar. wound repair regen. apr 2017;25(2):327-337. 10. blackstone bn, kim jy, mcfarland kl, et al. scar formation following excisional and burn injuries in a red duroc pig model. wound repair regen. aug 2017;25(4):618-631. 11. teiwes j, toto rd. epithelial sodium channel inhibition in cardiovascular disease. a skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 383 potential role for amiloride. am j hypertens. jan 2007;20(1):109-117. 12. xu w, hong sj, zeitchek m, et al. hydration status regulates sodium flux and inflammatory pathways through epithelial sodium channel (enac) in the skin. j invest dermatol. mar 2015;135(3):796-806. 13. grubauer g, elias pm, feingold kr. transepidermal water loss: the signal for recovery of barrier structure and function. j lipid res. mar 1989;30(3):323-333. 14. gardien klm, baas dc, de vet hcw, middelkoop e. transepidermal water loss measured with the tewameter tm300 in burn scars. burns. nov 2016;42(7):14551462. 15. jia sx, xie p, hong sj, galiano rd, mustoe ta. local application of statins significantly reduced hypertrophic scarring in a rabbit ear model. prs-glob open. jun 2017;5(6). 16. pathak r, dash rp, misra m, nivsarkar m. role of mucoadhesive polymers in enhancing delivery of nimodipine microemulsion to brain via intranasal route. acta pharm sin b. apr 2014;4(2):151-160. 17. wilgus ta, bergdall vk, tober kl, et al. the impact of cyclooxygenase-2 mediated inflammation on scarless fetal wound healing. the american journal of pathology. 2004;165(3):753-761. 18. zhou j, zhao y, simonenko v, et al. simultaneous silencing of tgf-β1 and cox2 reduces human skin hypertrophic scar through activation of fibroblast apoptosis. oncotarget. 2017-10-06 2017;8(46):8065180665. 19. wu j, ma b, yi s, et al. gene expression of early hypertrophic scar tissue screened by means of cdna microarrays. j trauma. dec 2004;57(6):1276-1286. 20. jabeen s, clough ecs, thomlinson am, chadwick sl, ferguson mwj, shah m. partial thickness wound: does mechanism of injury influence healing? burns. may 2019;45(3):531-542. 21. kirsner rs, eaglstein wh. the wound healing process. dermatol clin. oct 1993;11(4):629-640. 22. brissett ae, sherris da. scar contractures, hypertrophic scars, and keloids. facial plastic surgery. 2001-01-01 2001;17(04):263-272. 23. mari w, alsabri sg, tabal n, younes s, sherif a, simman r. novel insights on understanding of keloid scar: article review. j am coll clin wound spec. dec 2015;7(1-3):1-7. 24. shumaker pr, kwan jm, landers jt, uebelhoer ns. functional improvements in traumatic scars and scar contractures using an ablative fractional laser protocol. j trauma acute care. aug 2012;73:s116s121. skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 177 short communications oral contraceptive pills inducing bullous pemphigoid in an adolescent margaret c. wheless bs,1 blake r. zelickson md phd,1 tejesh s. patel md,1 allison v. jones md1 1university of tennessee health science center, memphis, tn an 18-year-old african-american female with past medical history of autism spectrum disorder and polycystic ovarian syndrome presented with a four-month history of tense bullae and superficial erosions 1-2 weeks after starting oral contraceptive pills: norethindrone acetate 1mg-ethinyl estradiol 20mcg-ferrous fumarate 75mg (figure 1). she discontinued the medication and the bullae resolved with a short course of methylprednisolone. a few weeks later she restarted the ocps resulting in a worse flare that did not respond to discontinuation or methylprednisolone. histopathology revealed a subepidermal vesicular dermatitis with eosinophils and direct immunofluorescence showed linear igg and c3 at the dermoepidermal junction, consistent with bullous pemphigoid. her bp180 antigen was 163. desmoglein 1, 3, and bp280 were all normal, a pregnancy test was negative, and a complete blood count and metabolic panel were unremarkable. she was started on 80mg prednisone daily with mild improvement that was unchanged with the addition of mycophenolate mofetil 1g twice daily. subsequently, she was treated with rituximab 1000mg, two doses two weeks apart which cleared all bullae. one month after rituximab treatment she presented with one tense bullae and was started on doxycycline 100mg twice daily, niacinamide 500mg twice daily, and topical triamcinolone 0.1% ointment, with clearance of bullae. of note, her bp180 four weeks following rituximab therapy was 63.6. figure 1. bullous pemphigoid on the extremities and trunk after starting oral contraceptive pills. skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 178 bullous pemphigoid (bp), recognized clinically by bullous skin lesions accompanied by pruritus, can be confirmed by biopsy findings revealing histopathological visualization of igg and c3 against the components of the hemidesmosome. bp antigens are monitored with serum levels of bp180 and, lesser so, bp230.1 bp180 constitutes part of the transmembrane hemidesmosome whose extracellular proteins can serve as a nidus for autoimmunity. bp180 levels help monitor the response to therapy in association with clinical improvement.4 this case represents a unique presentation of drug-induced bullous pemphigoid (dibp) in that bp is rare in adolescents with most patients presenting after age 70. cases in children are infrequent, with half occurring during the first year of life.1 in contrast with adults, childhood bp has a more indolent course with resolution after initial treatment. though many drugs are associated with the development of bp in adults, ocps have not been previously reported. progesterone has been known to induce autoimmune dermatoses, though not in association with ocps. progesterone could be the causal factor of the development of bp in our patient. though the mechanism is unknown, some suggest that synthetic progesterone induces molecular mimicry of the natural and synthetic hormones which may induce autoimmune disease.6 most cases of progesterone-associated autoimmune bullous dermatoses accompany pregnancy when progesterone levels are high. a case mentioning pemphigoid gestationis that resolved and later recurred with ocp use post-pregnancy has been reported.2 our patient represents a unique case in that she is an adolescent and not pregnant. two types of dipb have been reported. dipb-proper is self-limiting and resolves with cessation of the offending drug. the other resembles classical bp which takes a more severe, chronic course requiring treatment even after discontinuing the offending medicine.5 initial therapy is steroids. if the patient does not respond to oral prednisone, second line therapies are introduced such as azathioprine, mycophenolate mofetil, and tetracycline with niacinamide. tetracycline and niacinamide are used as secondary agents even though the data supporting their role is not as robust as the others.3 rituximab can be utilized for refractory cases.4 our patient required the use of rituximab as she did not improve with oral steroids or the addition of mycophenolate mofetil. though rituximab has been approved for treatment of pemphigus vulgaris, it has been shown to provide improvement in patients with bp.4 conflict of interest disclosures: none funding: none corresponding author: allison v. jones, md university of tennessee health science center department of dermatology 930 madison avenue, ste 840 memphis, tn 38163 phone: 901-448-5814 email: ajone180@uthsc.edu references: 1. amber, k., murrell, d., schmidt, e., joly, p. and borradori, l. (2017). autoimmune subepidermal bullous diseases of the skin and mucosae: clinical features, diagnosis, and management. clinical reviews in allergy & immunology, 54(1), pp.26-51. 2. honeyman, j., eguiguren, g., pinto, a., honeyman, a., de la parra, m. and navarrete, w. (1981). bullous dermatoses of skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 179 pregnancy. archives of dermatology, 117(5), pp.264-267. 3. kirtschig, g., middleton, p., bennett, c., murrell, df., wojnarowska, f., khumalo, np. (2010). interventions for bullous pemphigoid (review). cochrane database of systemic reviews, 10, pp. 1-62. 4. polansky, m., eisenstadt, r., degrazia, t., zhao, x., liu, y. and feldman, r. (2019). rituximab therapy in patients with bullous pemphigoid: a retrospective study of 20 patients. journal of the american academy of dermatology. 5. stavropoulos, p., soura, e. and antoniou, c. (2014). drug-induced pemphigoid: a review of the literature. journal of the european academy of dermatology and venereology, 28(9), pp.11331140. 6. tandon, v., mahajan, a. and sharma, s. (2008). tibolone induced bullous pemphigoid. jk science journal, 10(1), pp.26-27. fabior efficacy and tolerability across age gender and race poster aug 2017.pdf efficacy and tolerability of tazarotene foam 0.1% [fabior®] across age, gender, and race an integrated review of two phase iii trials rhonda schreiber bscn, mssl; kaytiana crane, bs; juhin patel, pharmd introduction results (integrated itt analysis set of the two studies) acne vulgaris is a complex disease with a diverse clinical presentation that affects males and females of all ages and ethnic backgrounds. topical retinoids are considered to be part of the first line treatment protocol for both inflammatory and non-inflammatory acne. there are various formulations of tazarotene on the market, however tazarotene foam 0.1% [fabior®] is an easy to apply, quickly absorbed, and elegant formulation that has been proven to have good tolerability and efficacy across a broad population of patients suffering from moderate to severe acne vulgaris. there has been very little comparative data published regarding efficacy and tolerability in sub-groups. the data presented here shows the utility of tazarotene foam 0.1% in clinical studies across age, gender, and race presenting with acne vulgaris. there were no meaningful between-group differences in demographics or disease characteristics, with the exception of a statistically significant different proportion of non-white subjects in the tazarotene group (24% vs 21%, p-0.014). mean reduction in non-inflammatory lesions was statistically significant at every visit (weeks 2, 4, 8, and 12). mean reduction in inflammatory lesions was statistically significant at weeks 8 and 12 conclusions while the overall efficacy of tazarotene foam 0.1% [fabior®] has been well established, there has been little emphasis on the breakdown across age, gender, and race. the data presented here has been extracted from the tazarotene foam 0.1% [fabior®] pivotal trials and shows clear efficacy in all groups barring the age group 36-45, which may have been affected by the small population size and/or disease characteristics in this demographic. the patient assessments, although blinded as to active or vehicle, showed that the proprietary foam technology used is positively rated in attributes that may affect patient adherence. the adverse reaction data reinforces that tazarotene foam 0.1% [fabior®] is similarly well tolerated across age, gender, and race. the data presented in this poster confirms that tazarotene foam 0.1% [fabior®] has a strong efficacy and tolerability profile across a broad demographic population. references & disclosures feldman, s. r., werner, c. p., & alio saenz, a. b. (2013). the efficacy and tolerability of tazarotene foam, 0.1%, in the treatment of acne vulgaris in 2 multicenter, randomized, vehicle-controlled, double-blind studies. journal of drugs in dermatology, 438-446. data on file. greenville, nc; mayne pharma, llc. zaenglein, a. l., pathy, a. l., schlosser, b. j., & et al. (2016). guidelines for the care and management of acne vulgaris. journal of the american academy of dermatology, 1-29. ms. schreiber, ms. crane, and dr. patel are employees of mayne pharma. the studies and presentation were sponsored by mayne pharma. less than 3% of patients discontinued use of tazarotene foam due to local skin reactions while subjects in the tazarotene foam 0.1% [fabior®] group experienced more adverse reactions initially vs the vehicle group, these peaked at week 2 and gradually reduced with continued use. tolerability in the tazarotene group was similar across age, gender, and race groups studied. methods study designs primary endpoints the absolute change in lesion counts (total, inflammatory, and non-inflammatory) from baseline to week 12 the proportion of participants who had a minimum 2-grade improvement in iga score from baseline to week 12 the proportion of participants who had an iga score of 0 (clear) or 1 (almost clear) at week 12 two multicenter, randomized, double-blind, vehicle controlled, parallel-group phase iii studies with 1485 patients who were randomized in a 1:1 ratio into two treatment groups tazarotene foam 0.1% (744) and vehicle foam (741) study products were applied to the affected areas (face, trunk, or both) once daily for 12 weeks and no other medications were allowed efficacy, safety and tolerability assessments were performed at baseline and weeks 2, 4, 8, and 12 efficacy was evaluated based on decrease in mean lesion counts and isga score from baseline to week 12 as assessed by investigators and tolerability was evaluated based on dryness, peeling, and erythema an ancova model was used in an intent to treat (itt) analysis to determine absolute change in total, inflammatory, and non-inflammatory lesion counts from baseline to week 12 0.0% 22.0%* 36.1%* 49.6%* 56.1%* 0.0% 18.0% 29.1% 37.0% 40.8% 0% 10% 20% 30% 40% 50% 60% baseline week 2 week 4 week 8 week 12 m e a n % r e d u c ti o n i n t o ta l le s io n s tazarotene foam (n=744) vehicle foam (n=741) *p<0.001 29.0% 22.3% 31.9% 15.7% 10.3% 12.8% 0% 5% 10% 15% 20% 25% 30% 35% caucasian (n=1150) african american (n=219) other (n=116) % o f s u b je c ts tazarotene foam vehicle foam 32.7% 23.6% 15.9% 13.5% 0% 5% 10% 15% 20% 25% 30% 35% females (n=756) males (n=729) % o f s u b je c ts tazarotene foam vehicle foam 25.2% 31.7% 35.6% 27.3% 10.4% 18.8% 17.1% 40.6% 0.0% 5.0% 10.0% 15.0% 20.0% 25.0% 30.0% 35.0% 40.0% 45.0% ages 12 17 (n=860) ages 18 25 (n=428) ages 26 35 (n=143) ages 36 45 (n=54) % o f s ub je ct s tazarotene foam vehicle foam objectives evaluate the efficacy and tolerability of tazarotene foam 0.1% [fabior®] across age, gender, and race present the favorable qualities of a foam formulation of tazarotene efficacy with tazarotene foam 0.1% [fabior®] was statistically significant and similar across age, gender, and race groups studied versus vehicle foam with the exception of the group aged 36 45. the foam vehicle received favorable quality ratings in questionnaires completed by patients. 84% 81% 72% 70% 61% 62% 60% 34% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% easy to apply spreadability absorbs quickly lack of stickiness fragrance-free does not feel greasy lack of residue moisturizing % o f s u b je c ts p<0.001 p=0.026 p=0.017 p<0.001 p=0.002 p=0.015 p=0.329 (ns) p<0.001 tazarotene foam (n=744) vehicle foam (n=741) patients with any ars 22% 3% application site irritation 14% 1% application site dryness 7% 1% application site erythema 6% <1% application site exfoliation 6% <1% application site pain 1% 0 application site photosensitivity (including sunburn) 1% <1% application site pruritis 1% <1% application site dermatitis 1% <1% adverse reactions in ≥1% of patients tazarotene foam (n=744) males (n=729) 22% females (n=756) 22% age 12 17 (n=860) 22% age 18 25 (n=428) 19% age 26 35 (n=143) 29% age 36 45 (n=54) 27% caucasian (n=1150) 21% african american (n=219) 24% other (n=116) 23% mean % reduction in total lesions vs. baseline over time treatment success* by race treatment success* by age treatment success* by gender **top 2 box score (categories: excellent and good) patient demographics n (%) males 729 (49) females 756 (51) age 12 17 860 (58) age 18 25 428 (29) age 26 35 143 (10) age 36 45 54 (4) hispanic or latino 260 (18) not hispanic or latino 1225 (82) caucasian 1150 (77) african american 219 (15) asian 63 (4) other 53 (4) baseline isga 3 1192 (80) baseline isga 4 293 (20) patient assessment of foam vehicle attributes** *treatment success was defined as a minimum 2-grade improvement in iga score and a score of 0 or 1 at study end (week 12) powerpoint presentation a comprehensive diagnostic offering workflow increases the rate of actionable results of the 23and 35-gene expression profile tests for use as ancillary diagnostic tools for difficult-to-diagnose melanocytic lesions background methods › diagnostic discordance in suspicious cutaneous melanocytic lesions is well documented and particularly prevalent among difficult-to-diagnose cases, for which histopathology may be insufficient for a definitive diagnosis.1-4 › the 23-gene expression profile (gep; mypath melanoma) and 35-gep (diffdx-melanoma) tests are clinically available objective ancillary tools that facilitate diagnosis of melanocytic lesions with ambiguous histopathology. the tests use proprietary algorithms to produce results of likely benign, intermediate, or malignant.5-7 › the 23-gep has shown accuracy metrics of over 90% sensitivity in multiple clinical studies that included patient outcomes.8-10 however, the 23-gep historically has resulted in ~23% of cases receiving either a technical failure or an intermediate result, which can be perceived as nonactionable.6,11-13 the 35-gep test can address this shortcoming and showed both an increased sensitivity in the first validation cohort and a decreased nonactionable rate of 8.5%.7 › clinical utility has been demonstrated with benign and malignant gep test results;11,14 therefore, those test results are defined as actionable. acknowledgments & disclosures references › this study was sponsored by castle biosciences, inc. › all authors are employees and shareholders of castle biosciences, inc. 1. shoo, b. a. et al. j am acad dermatol 2010. 62 (5) 751–756. 2. gerami, p. et al. am j surg pathol 2010. 34 (6) 816–821. 3. haws, b. et al. j cutan pathol 2012. 39 (9) 844–849. 4. elmore, j. g. et al. bmj 2017. 357 (1) j2813. 5. clarke, l. e. et al. j cutan pathol 2015. 42 (4) 244–252. 6. clarke, l. e. et al. cancer 2017. 123 (4) 617–628. 7. estrada, s. et al. skin 2020. 4 (6) 506–522. 8. ko, j. s. et al. cancer epidem biomar prev 2017. 26 (7) 1107–1113. 9. ko, j. s. et al. human pathology 2019. 86 213–221. 10. clarke, l. e. et al. personalized medicine 2020. 17 (5) 361–371. 11. cockerell, c. j. et al. medicine 2016. 95 (40) e4887. 12. minca, e. c. et al. mod pathol 2016. 29 (8) 832–843. 13. castillo, s. a. et al. am j dermatopathol 2020. 42 (12) 939-947. 14. farberg, a. et al. skin 2020. 4 (6) 523–533. results matthew s goldberg, md1,2, jennifer j siegel, phd1, brooke h russell, phd1, jason h rogers, msc1, kyle r covington, phd1, kristen m oelschlager, rn1, trisha m poteet1, jeffrey k wilkinson, phd1, michael d berg, phd1, katherine falkowski, phd1, sarah j kurley, phd1, and armineh kajoian, md1 1castle biosciences, inc., friendswood, tx 2icahn school of medicine at mount sinai, new york, ny for more information: mgoldberg@castlebiosciences.com objective › today, both the 23and 35-gep are offered from a single laboratory as part of a comprehensive diagnostic offering (cdo) workflow. unless preferred otherwise by the ordering clinician, clinical samples are processed first through the 23-gep test, and if a technical failure or intermediate result is received, processed to the 35-gep (figure 1). › here, we report test result metrics from archival research cases and from this clinical workflow. › combining the 23-gep and 35-gep tests into one workflow leverages the strengths of both assays. › the cdo workflow demonstrated a high rate of accuracy in research cases, with 94.7% sensitivity and 89.5% specificity. › the cdo workflow for ambiguous melanocytic lesions has substantially improved reporting of clinically actionable results from a historic rate of ~77% for the 23-gep alone to over 98%. › eligible cases with a malignant result from the cdo can also be subsequently run on the 31-gep prognostic test (decision dx-melanoma), without requiring extra tissue, to predict the likelihood of recurrence and sentinel lymph node biopsy positivity. conclusions figure 1. clinical workflow of the comprehensive diagnostic offering *does not generate a test report. cases with intermediate or technical fail results from the 23-gep undergo testing with the 35-gep. gep, gene expression profile. › melanocytic lesions and associated de-identified clinical data from patients ≥18 years of age were included in this study. samples were acquired under an irb-approved protocol or were previously submitted for clinical testing for the 31-gep. research samples were independently reviewed by at least 2 dermatopathologists for diagnostic adjudication, were blinded to the original diagnosis, and included in the study if they received at least 2 out of 3 diagnostic concordance (table 1). the study also included clinical cases submitted to castle biosciences for cdo testing with results reported since implementation of the cdo workflow between june 3 and august 31, 2021 (table 2). › all cases not receiving a benign or malignant result from the 23-gep were run on the 35-gep, except for pediatric cases (<18 years), which were only run on the 23-gep and excluded from this analysis. technical fail included samples with insufficient quantity of rna and/or control or discriminant gene amplification failure based on the requirements for each test. scan or click here for more info › clinical test results were analyzed over a 3-month period. › the 23-gep test gave an actionable result of benign or malignant in 77.8% of cases, which is comparable to past reporting in ambiguous cases for this test6,11 (table 2). › nonactionable classifications of the 23-gep test were 22.2% (12.9% intermediate and 9.4% technical failure). these cases then underwent testing with the 35-gep test, and an additional 20.9% of originally submitted cases received an actionable result. only 1.1% of cases received a final intermediate test result (i.e., from both tests); the technical failure rate for the cdo was 0.2% (table 2). › this clinical workflow increased the rate of an actionable report from 77.8% to 98.7% when compared with 23-gep testing alone (table 2). › the clinical workflow results were 59.5% benign, 39.1% malignant, 1.1% intermediate, and 0.2% technical failure. melanocytic lesion of uncertain malignant potential 23-gep benign intermediate or technical fail* 35-gep benign intermediate technical fail* malignant malignant table 2. clinical test results of the comprehensive diagnostic offering cases with intermediate or technical fail results from the 23-gep undergo testing with the 35-gep. gep, gene expression profile. research cohort, n=738 cdo 95% ci sensitivity 94.7% 92.4-96.8 specificity 89.5% 86.3-92.7 ppv 90.1% 87.7-93.4 npv 94.1% 91.4-96.4 intermediate 0.8% n=6 clinical cdo testing actionable (%) nonactionable (%) 23-gep alone 77.8% 22.2% subsequent 35-gep 20.8% 1.3% overall 98.7% 1.3% › the research cohort was comprised of 738 ffpe archival biopsy samples from adults ≥18 years of age with cutaneous melanocytic lesions with a consensus diagnosis reviewed by at least three independent dermatopathologists who were blinded to the original diagnosis. all samples were run on the 23-gep, and any intermediate or technical fail samples were subsequently run on the 35-gep per the current clinical cdo workflow (figure 1). › accuracy metrics demonstrate high performance of the cdo workflow (table 1). table 1. accuracy metrics in research cases from the comprehensive diagnostic offering npv, negative predictive value; ppv, positive predictive value; ci, confidence interval. https://castletestinfo.com/ skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 418 brief article invasive trichosporonosis in a child following chemotherapy induction valerie m. foy1, emily mceldrew, do2, chelsea kesty, md2, kristina lim, do2, kevin liu, do2, haider asad, md3, cynthia bartus, md2 1 philadelphia college of osteopathic medicine, philadelphia, pa 2 lehigh valley health network, department of dermatology, allentown, pa 3 lehigh valley health network, department of pathology, allentown, pa a 2-year-old caucasian female presented to the hospital with fatigue and dyspnea on exertion. her lab work revealed leukocytosis, anemia, and thrombocytopenia, and subsequent spinal tap was diagnostic of acute b cell lymphoblastic leukemia. the patient began induction chemotherapy with vincristine and mercaptopurine, together with stress dose hydrocortisone and trimethoprimsulfamethoxazole. two weeks later, she developed neutropenia, fevers, port site erythema, and new painful lesions on her legs. she was empirically started on vancomycin, cefepime and micafungin. on physical exam, there were multiple tender hyperpigmented nodules scattered on the lower extremities (figure 1). an mri of bilateral lower legs was performed and demonstrated extensive infectious myositis with numerous foci of peripheral ring enhancement, concerning for developing abscesses. an mri of her lumbar spine revealed multiple lesions, possible fluid collections or abscesses, in the lower posterior paraspinal muscles and subcutaneous soft tissues. a punch biopsy of her lower leg showed deep mixed suppurative and granulomatous inflammation with multiple yeast and hyphal forms (figure 2). the tissue culture was positive for trichosporon asahii. notably, anaerobic/aerobic culture, acid-fast bacilli culture, blood culture, and bone marrow aspirate were all negative. the patient was started on amphotericin b for treatment of invasive trichosporonosis and her port site was surgically debrided. she was ultimately discharged on oral voriconazole monotherapy and has continued therapy for 8 months. abstract trichosporonosis is an opportunistic fungal infection that commonly affects neutropenic, immunocompromised patients. we report a case of invasive trichosporonosis in a child with acute lymphoblastic leukemia following the induction of chemotherapeutic agents. case report skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 419 figure 1. hyperpigmented nodules scattered across the bilateral lower extremities. figure 2. punch biopsy of lower leg nodules showing deep mixed suppurative and granulomatous inflammation with multiple yeast and hyphal forms. trichosporonosis is an opportunistic fungal infection caused by trichosporon species, with t. asahii most identified as the cause of disseminated infection.1 trichosporon species are basidiomycetous yeast-like fungi that have been known to colonize the skin, gastrointestinal tract, and mucosal surfaces. trichosporonosis primarily affects immunocompromised patients with neutropenia and may only cause allergic pneumonitis or superficial skin infections in immunocompetent hosts. 3 it is the second most common fungal infection in patients with hematologic malignancy, with aspergillus being the leading cause.1 there are several risk factors for invasive disease including solid organ transplant, hiv, extensive burns, invasive medical equipment, chronic kidney disease, cystic fibrosis, and peritoneal dialysis.1 the mortality rate of disseminated disease is estimated to be 50-80%.1 disseminated trichosporonosis typically presents with prolonged fever unresponsive to antibiotics, pulmonary infiltrates, acute renal failure, and hepatic and/or splenic abscesses.2 cutaneous manifestations include painless papules, pustules, nodules, ulcers, exophytic growths, and soft tissue infections. a morbilliform rash has previously been reported in the literature on two separate occasions.4,5 other systemic findings include brain abscesses, meningitis, endocarditis, and myositis. histological examination will reveal budding yeasts that enhance with periodic acid methenamine silver staining; however, the diagnosis should be confirmed with a tissue culture. blood and urine cultures may also be of additional clinical utility. voriconazole is the current drug of choice for disseminated trichosporonosis, as multiple studies suggest it is superior to other azoles, including fluconazole and itraconazole.2 other options for treatment include amphotericin b and flucytosine. notably, echinocandins such as micafungin and caspofungin have no activity against trichosporon species and are therefore not recommended.2 in fact, careful consideration should be taken in deciding whether to start echinocandin prophylaxis, discussion skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 420 given the risk of antifungal pressure selecting for pathogens associated with high mortality.6 ultimately, cure of trichosporonosis depends on source control with surgical intervention, adequate antifungal therapy, and reversal of neutropenia. conflict of interest disclosures: none funding: none corresponding author: valerie foy philadelphia college of osteopathic medicine email: vf8787@pcom.edu references: 1. aslinur op, eda ko, ali bc, et al. trichosporon asahii sepsis in a patient with pediatric malignancy. journal of microbiology, immunology and infection. 2016; 49 (1): 146-149. 2. nguyen m, naeem f, razzaqi f, vijayan v. invasive trichosporonosis in a 2-year-old with acute lymphoblastic leukemia. j pediatr hematol oncol. 2021; 43 (8): e1254-e1255. 3. colombo al, padovan ac, chaves gm. current knowledge of trichosporon spp. and trichosporonosis. clin microbiol rev. 2011;24(4):682-700. 4. nguyen jk, schlichte mj, schady d, pourciau cy. fatal disseminated trichosporon asahii fungemia in a child with acute lymphoblastic leukemia and a morbilliform eruption. pediatric dermatology. 2017; 35 (1): e86-e87. 5. cardenas-de la garza ja, ancer-arellano j, cuellar-barboza a, et al. disseminated trichosporon asahii infection in a patient with acute myeloid leukemia. j dermatol. 2019;46(4):e128-e129. doi:10.1111/13468138.14662. 6. mahoney d, aftandilian c. breakthrough trichosporon asahii in a patient with new diagnosis b-all on echinocandin prophylaxis: a case report. journal of pediatric hematology/oncology. 2022; 44 (2):e514-e517. skin january 2018 volume 2 issue 1 copyright 2018 the national society for cutaneous medicine 85 brief articles granulomatous mastitis as a presentation of sarcoidosis andrea d. maderal md a , daniel g. federman md b , robert s. kirsner md, phd a a university of miami miller school of medicine, miami, fl b va connecticut healthcare system and yale university school of medicine, west haven, ct a 31-year-old african-american woman, g3p2002, presented 26 weeks pregnant to her obstetrician with a painful, red tumor in her right breast. a breast ultrasound did not show any drainable collection; she was diagnosed with mastitis and treated with dicloxacillin for 2 weeks. one month later, she was seen at an outside hospital with new onset weakness, arthralgias and myalgias, so severe that she needed a walker for ambulation. she received systemic intravenous antibiotics with cefazolin and oseltamivir. during her hospitalization, she developed red tender nodules on both legs and forearms, as well as redness and discomfort in her right eye. she also had a mild non-productive cough but denied fevers, chills, oral ulcers, dry mouth, shortness of breath, hemoptysis, chest pain, gastrointestinal symptoms or hematuria. she was otherwise in good health. her only medications included prenatal vitamins. there was no family history of autoimmune disease or sarcoidosis. she denied any recent travel. on physical examination, she was afebrile but tachycardic with heart rate ranging from 110-120. her lungs were clear to auscultation, and there was non-pitting edema of her legs to the knees. she did not have joint redness, tenderness or swelling and muscle strength was normal. on skin examination, she had a 5 x 13 cm indurated mass in her right breast with associated tender, rubbery lymphadenopathy in the right axilla, (fig. 1) as well as red tender subcutaneous nodules on her anterior legs (fig. 2) and forearms. abstract sarcoidosis is an idiopathic inflammatory disease characterized by granuloma formation in various tissues, most commonly the lungs, lymphatics, skin and eyes. involvement of the breast in sarcoidosis is rare, and can be defined into three subsets, including granulomas localized to the breast, referred to as breast sarcoidosis. breast sarcoidosis may present with systemic findings such as erythema nodosum, arthritis, and uveitis, and unlike typical sarcoidosis, commonly manifests during pregnancy. in this report, we present a rare case of breast sarcoidosis presenting in a pregnant female with associated erythema nodosum, arthralgias and ocular complaints. case report skin january 2018 volume 2 issue 1 copyright 2018 the national society for cutaneous medicine 86 she had a normal complete blood count (cbc) and complete metabolic profile (cmp). her c-reactive protein (crp) and erythrocyte sedimentation rate (esr) were highly elevated at 19.6 and 100, respectively. quantiferon gold was negative and angiotensin converting enzyme (ace) level was normal. further infectious and autoimmune serologies were negative and she had an anti-nuclear antibody (ana) of 1:40. chest radiograph (cxr) did not show consolidation or lymphadenopathy. breast ultrasound and mammogram showed birads 3 (probably benign), likely from an inflammatory process. breast biopsy showed non-caseating granulomas. (fig. 3) swab and tissue cultures for bacterial, fungal and mycobacterial organisms were negative. the patient was diagnosed with sarcoidosis with a presentation of erythema nodosum, arthralgias, granulomatous mastitis and ocular complaints (ophthalmology had not been consulted at the time of presentation). treatment with prednisone 20 mg daily resulted in complete resolution of erythema nodosum lesions, ocular complaints, and arthralgias, and significant reduction in the breast mass. post-uncomplicated delivery, computed tomography (ct) of the chest and electrocardiogram (ekg) were within normal limits, and the patient’s symptoms were well maintained on prednisone 10 mg daily. figure 1. red to violaceous ulcerated plaques on the right breast. skin january 2018 volume 2 issue 1 copyright 2018 the national society for cutaneous medicine 87 figure 2. red subcutaneous nodules on the anterior leg. figure 3. histopathologic specimen taken from the breast revealing noncaseating granulomas. this patient presented with breast involvement of sarcoidosis, which is rare. breast involvement in sarcoidosis is classified into three categories: sarcoidosis patients with breast cancer, breast cancer patients showing sarcoidosis-like breast reactions, and sarcoidosis patients with breast granulomas, which is referred to as breast sarcoidosis. 1 the latter presentation of breast sarcoidosis is rare and accounts for less than 1% of cases of breast involvement of sarcoidosis. a total of 51 cases of breast sarcoidosis have been reported with approximately one quarter (23%) as the initial presentation. 2 in those 51 cases, the mean age of onset was 48 years and the most frequent presentation is of a palpable mass concerning for breast cancer. diagnosis is achieved by core biopsy revealing non-caseating granulomas, without evidence of adjacent malignancy. numerous reports of idiopathic granulomatous mastitis, occurring most frequently in parous young women between the ages 30-40, usually within a few years after giving birth or during pregnancy exist. 3 in some of these patients, extra-mammary findings including erythema nodosum, arthralgias and episcleritis have been reported and these may represent a form fruste of sarcoidosis. 4 though sarcoidosis is typically reported to be rare in pregnancy, reports of idiopathic granulomatous mastitis occurring during pregnancy are likely presentations of breast sarcoidosis, and thus the prevalence of sarcoidosis in pregnancy may be underestimated. 5 sarcoidosis is an idiopathic systemic disease characterized by the formation of granulomas in various tissues, most commonly the lungs, lymphatic tissue, skin and eyes. the prevalence ranges from 4.763 in 100,000, and is more common in women, and in african-americans. 6 the pathogenesis is largely unknown, but is thought to be due to an exaggerated immune response to unidentified antigens, discussion skin january 2018 volume 2 issue 1 copyright 2018 the national society for cutaneous medicine 88 either through an autoimmune phenomenon, or as reaction to underlying infection, including possibly mycobacteria. the inflammatory response is characterized by upregulation of th1 cd4+ cells, causing increased production of il-2, ifn-gamma and tnf-alpha, with resultant epithelioid granuloma formation. 7 clinical manifestations of sarcoidosis vary based on degree and location of tissue involvement. lung disease is seen in approximately 90% of patients with sarcoidosis. 8 lymphatic involvement is also common, and typically presents with bilateral hilar lymphadenopathy. skin disease is seen in 30% of patients, and histologic specific lesions include papules, nodules, plaques or subcutaneous nodules due to granuloma formation in the skin. 9 nonspecific lesions include erythema nodosum. bilateral ankle arthritis can be seen in 7-28% of patients. 10 sarcoidosis is diagnosed by clinical and radiological presentation, evidence of noncaseating granulomas on histology, and lack of evidence for other diseases. 10 as a diagnosis of exclusion, other granulomaforming conditions, including infections (most commonly tuberculosis or fungal disease), occupational or environmental induced granulomas, drug-induced granulomas and other idiopathic granulomatoses should be considered and excluded. 6 diagnostic work-up in patients with sarcoidosis includes a thorough history and physical examination. if any cutaneous lesions are present, skin biopsy should be performed. laboratory studies can include a cbc, cmp (to evaluate for renal or liver involvement), esr and ace level. elevated ace levels are seen in 60% of patients with sarcoidosis and can be used to monitor disease activity. internal organ involvement should be screened for with an ophthalmology evaluation, chest x-ray, pulmonary function tests, and ekg. treatments for sarcoidosis are most commonly employed with oral corticosteroids. other treatments that can be effective include immunosuppressive agents such as methotrexate, azathioprine, leflunomide, cyclophosphamide, mycophenolate mofetil; tnf-alpha suppressants such as pentoxyfilline, thalidomide, and tnf-alpha inhibitors; and anti-inflammatory antimicrobial agents such as antimalarials and tetracycline derivatives. 6 conflict of interest disclosures: none. funding: none. corresponding author: robert s. kirsner, md, phd 1600 nw 10 th avenue rmsb 2023a miami, fl 33136 rkirsner@med.miami.edu references: 1. lower ee, hawkins hh, baughman rp. breast disease in sarcoidosis. sarcoidosis vasc diffuse lung dis. 2001;18:301-6. 2. mona el k, pascal c, charley h, francoise b, veronique b, mariemadeleine p. quiz case. breast sarcoidosis presenting as a metastatic breast cancer. eur j radiol. 2005;54:25. skin january 2018 volume 2 issue 1 copyright 2018 the national society for cutaneous medicine 89 3. altintoprak f, kivilcim t, ozkan ov. aetiology of idiopathic granulomatous mastitis. world j clin cases. 2014;2:852-8. 4. fahmy j, halabi-tawil m, bagot m, tournant b, petit a. erythema nodosum during the course of idiopathic granulomatous mastitis. ann dermatol venereol. 2015;142:46-9. 5. hadid v, patenaude v, oddy l, abenhaim ha. sarcoidosis and pregnancy: obstetrical and neonatal outcomes in a population-based cohort of 7 million births. j perinat med. 2015;43:201-7. 6. valeyre d, prasse a, nunes h, uzunhan y, brillet py, muller-quernheim j. sarcoidosis. lancet. 2014;383:1155-67. 7. kataria yp, holter jf. immunology of sarcoidosis. clin chest med. 1997;18:719-39. 8. sheffield ea. pathology of sarcoidosis. clin chest med. 1997;18:741-54. 9. judson ma. extrapulmonary sarcoidosis. semin respir crit care med. 2007;28:83-101. 10. joint statement of the american thoracic society (ats) the european respiratory society (ers) the world association of sarcoidosis and other granulomatous disorders (wasog) adopted by the ats board of directors and by the ers executive committee, february 1999. am j respir crit care med. 1999;160:736-55. skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 542 brief article il-17a blockade treatment success in erythrodermic pityriasis rubra pilaris wylie masterson ,bsa1, daniel morse, md2, omar pacha, md2 1 department of dermatology, the university of texas health science center, houston, tx 2 department of dermatology, the university of texas md anderson cancer center, houston, tx pityriasis rubra pilaris (prp) is a rare inflammatory skin disease of unknown etiology and without a clear treatment algorithm. lesional skin of patients with prp demonstrates increased levels of the cytokines, il-17a, il-17f, and il-22. correspondingly, il-17a inhibitors, such as secukinumab, has been reported to effectively treat prp.1 il-23 inhibition has not been attempted in the treatment of prp though it acts in the same inflammatory cascade.2 we present a case of new onset erythrodermic prp successfully treated with il-17a blockade. a 63-year-old man with hashimoto’s thyroiditis and type 1 diabetes mellitus presented with a new onset, diffuse erythematous rash and waxy palmoplantar keratoderma. the rash began four months earlier as an erythematous patch on the patient’s scalp which spread cephalocaudally to cover his entire body over the next month. he reported severe pruritus, worsening of the rash with sun exposure, and new alopecia on his parietal scalp. on presentation, he had diffuse salmon colored erythema with distinct ‘islands of sparing’ and significant palmar and plantar waxy keratoderma (figure 1). the differential diagnoses included erythrodermic psoriasis, erythrodermic mycosis fungoides, sezary syndrome, abstract background: pityriasis rubra pilaris is an inflammatory skin disease with no known etiology or treatment algorithm. prp patients have an increase in cytokines il-17a, il-17f, and il-22. there are case reports and series that study treatment with agents that block these cytokines, but more research is needed. our objective is to add to the literature on treatment of prp with il-17a blockers. case: a 63-year-old man presented with erythrodermic pityriasis rubra pilaris that was diagnosed after biopsy and laboratory tests ruled out other conditions such as psoriasis and sezary syndrome. he was successfully treated with il-17 blockade. conclusion: our case demonstrates the successful use of il-17a blockade for prp, which suggests that it could be an effective future treatment. introduction case skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 543 erythrodermic drug eruption, erythroderma secondary to malignancy, and prp. labs revealed 19% eosinophils and a figure 1. a) pictured is the patient’s red orange (salmon) colored erythema and fine flaky scaling involving 95% of his body surface b) there is bilateral toenail and fingernail plates with yellowing, thickening, subungual debris and onycholysis with no pitting b-d) there is evident palmar-plantar hyperkeratosis and waxy keratoderma. normal white blood cell count. skin biopsy revealed vertical and horizontal alternating orthokeratosis and parakeratosis. a thickened granular layer, short thicker rete ridges, and limited vascular dilation in the dermal papillae were seen. (figure 2). tcell receptor testing revealed no abnormal gene rearrangements and flow cytometry failed to reveal aberrant cells. these features were considered compatible with prp. the patient originally presented to an outside dermatologist one month after the rash began who started the patient on acitretin 25 mg in the morning and 17.5 mg in the evening, hydroxyzine 25 mg, and 0.1% triamcinolone ointment. two months after rash presentation, he was started on risankizumab with an initiation dose of 150 mg at week 0 and week 4. this was followed by maintenance dosing of 150 mg every three months. after three months of no improvement while on risankizumab and four months since the rash began, he presented to our institution. we discontinued the risankizumab, increased his acitretin to acitretin 25 mg twice daily, and continued the 0.1% triamcinolone ointment wet wraps. later that month we started him on secukinumab with an initiation dose of 300 mg injections weekly for the first four weeks and then monthly thereafter for maintenance. two months after initiating secukinumab his pruritus and skin discomfort had improved but his erythroderma was persistent. two months after improvement on the secukinumab, methotrexate was added as an additional therapy, and his acitretin was stopped. three months later, he had nearly complete resolution of his erythroderma, keratoderma, scaling, and pruritus. at last follow-up seven months after starting the secukinumab and five months after starting the methotrexate, he is stable and will remain on both treatments. prp is a rare inflammatory skin disease with no known etiology and no established treatment algorithm.3 it typically presents with salmon colored diffuse erythema with distinct ‘islands of sparring’, that starts on the head or neck and then spreads cephalocaudally. other features include follicular hyperkeratosis, irregular hyperpigmentation, palmar and plantar waxy keratoderma, and pruritus. nail findings in prp can include subungual hyperkeratosis, yellow discoloration, nail plate thickening, discussion skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 544 splinter hemorrhages and the absence of nail pitting.3 figure 2. a-c) moderately acanthotic epidermis with alternating hyperkeratosis and parakeratosis and retention of the granular layer a) mild lymphocyte exocytosis was noted as well as a mild superficial perivascular lymphohistiocytic inflammatory infiltrate. histologically, prp is marked by irregular acanthosis, alternating vertical and horizontal orthohyperkeratosis and parakeratosis, irregular acanthosis with thickened suprapapillary plates, and preservation of the stratum granulosum.4 clinically, our differential diagnoses included erythrodermic psoriasis, erythrodermic mycosis fungoides, sezary syndrome, and erythrodermic drug eruption. prp and erythrodermic psoriasis are frequently mistaken for each other. a helpful clue in distinguishing the entities is the presence of nail pitting, which is expected in psoriasis, but not in prp. additionally, prp exhibits a waxy keratoderma or “carnauba wax” appearance of the palms and soles that is not present in psoriasis. in our case, erythrodermic mycosis fungoides was unlikely based on histology, and there was no abnormal t-cell gene rearrangement. t-cell receptor testing revealed no abnormal gene rearrangements and flow cytometry failed to reveal aberrant cells which excluded sezary syndrome. finally, no new medication or medication changes made erythrodermic drug eruption unlikely. interestingly, in skin lesions of prp patients, studies found an upregulation of helper tcell 17 cytokines including il-17a, il-17f, and il-22,5 which suggests that the il-23th17 pathway plays an important role in this condition. il-23 helps activate th17 cells by contributing to jak and tyr-residue phosphorylation. this phosphorylation causes an increase in il-17a, il-17f, tumor necrosis factor, and il-6 production as well as an increase in keratinocyte proliferation.6 these cytokines are targets of therapies including il-23 and il-17 inhibitors which are now being used to treat skin diseases such as psoriasis and prp.7 secukinumab, a human igg1 anti-il17a antibody, skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 545 selectively binds to il-17a cytokines. this prevents binding of the cytokine to its receptor, which inhibits the release of proinflammatory cytokines from th-17 cells.7,11 the inhibition of il-17 can lead to successful treatment of prp, which is shown in previous case reports, series, and review articles.2, 8-10 in conclusion, we present a case of prp that was successfully treated with secukinumab and methotrexate. the patient was not on risankizumab for long enough to determine its effect. this case is limited by the natural course of prp, so it impossible to know whether our treatment led to his resolution – his treatment has not yet been held. however, our report adds to the body of literature suggesting il-17 inhibition as effective treatment for prp which supports the research on the il-23-th17 pathway in prp. conflict of interest disclosures: none funding: none corresponding author: daniel morse md, department of dermatology, the university of texas health science center 1400 pressler st, houston, tx 77030 phone: (713)563-1665 fax: (713)745-3597 e-mail: daniel.c.morse@uth.tmc.edu references: 1. wain t, secukinumab in pityriasis rubra pilaris: a case series demonstrating variable response and the need for minimal clinical datasets. jaad case rep.2018 2. brembilla, nicolo costantino, luisa senra, and wolf-henning boehncke. “the il-17 family of cytokines in psoriasis: il-17a and beyond.” frontiers in immunology 9 (2018): 1682–1682. web. 3. sonnex, t. s et al. “the nails in adult type 1 pityriasis rubra pilaris: a comparison with sézary syndrome and psoriasis.” journal of the american academy of dermatology 15.5 (1986): 956–960. print. 4. brown f, badri t. pityriasis rubra pilaris. [updated 2020 jun 29]. in: statpearls [internet]. treasure island (fl): statpearls publishing; 2020 jan-. 5. feldmeyer, laurence et al. “interleukin 23– helper t cell 17 axis as a treatment target for pityriasis rubra pilaris.” jama dermatology (chicago, ill.) 153.4 (2017): 304–308. web. 6. liu, taoming et al. “the il-23/il-17 pathway in inflammatory skin diseases: from bench to bedside.” frontiers in immunology 11 (2020): 594735–594735. web. 7. wasilewska a, winiarska m, olszewska m, rudnicka l. interleukin-17 inhibitors. a new era in treatment of psoriasis and other skin diseases. postepy dermatol alergol. 2016;33(4):247252. doi:10.5114/ada.2016.61599 8. schuster d, pfister-wartha a, brucknertuderman l, schempp cm. successful treatment of refractory pityriasis rubra pilaris with secukinumab. jama dermatol. 2016;152(11):1278–1279. doi:10.1001/jamadermatol.2016.3885 9. schuster, daniel et al. “successful treatment of refractory pityriasis rubra pilaris with secukinumab.” jama dermatology (chicago, ill.) 152.11 (2016): 1278–1279. web. 10. wu, kevin k, and harry dao. “off-label dermatologic uses of il-17 inhibitors.” the journal of dermatological treatment ahead-ofprint.ahead-of-print 1–7. web. 11. fala l. cosentyx (secukinumab): first il-17a antagonist receives fda approval for moderate-to-severe plaque psoriasis. am health drug benefits. 2016;9(spec feature):6063. conclusion acknowledgements study funded by galderma research & development, snc, and editorial/poster support provided by galderma laboratories, l.p. methods study design • objectives – this analysis reviews the consistency of efficacy and safety results of 4 (two phase 2 and 2 phase 3) 12-week, vehicle-controlled studies (n = 1683) conducted during the development of ivm. • methods – phase 2, study 1 · 6-arm, 12 week, dose ranging, multicenter, randomized, investigator-blind, vehicle and active-controlled study ivermectin 0.1%, qd; ivermectin 0.3%, qd; ivermectin 1%, qd; ivermectin 1%, bid ; metronidazole 0.75%, bid; and vehicle, qd · subjects were male or female, ≥ 18 years of age, with ppr (≥ 15 lesions) · for the sake of consistency of this analysis, only data from the ivermectin 1% and the vehicle qd arms are reported here. – phase 2, study 2 · 12 week, multicenter, prospective, randomized, double-blind, vehicle-controlled study ivermectin 1%, qd; vehicle, qd · subjects were male or female, ≥ 18 years of age, with ppr (≥ 15 lesions) – phase 3, study 1 and 2 · two 12 week, multicenter, randomized, double-blind, parallel-group, vehiclecontrolled studies of identical design ivermectin 1%, qd; vehicle, qd · subjects were male or female, ≥ 18 years of age, with ppr (≥ 15 lesions) – endpoints · iga success (iga 0 or 1; iga scale 0 [clear] to 4 [severe]) · lesion counts (absolute change and mean percent reduction from baseline) · tolerability · adverse events results efficacy • 1683 subjects in 4 studies (two phase 2, two phase 3) are included in this analysis • all 4 studies confirmed the statistical superiority of ivm vs vehicle – success rate (iga 0 or 1) was statistically superior for ivm vs vehicle in all 4 studies (figure 1) · phase 2 studies: a statistically superior rate of success was seen, compared to vehicle 65.4%; week 12, phase 2, study 1, n = 102, p < .05 55.8%; week 12, phase 2, study 2, n = 210, p < .01 · phase 3 studies: a statistically superior rate of success was seen, compared to vehicle 38.4%; week 12, phase 3, study 1, n = 683, p < .001 40.1%; week 12, phase 3, study 2, n = 688, p < .001 – lesion reduction was statistically superior for ivm vs vehicle in all 4 studies (figure 2). safety • the treatment was highly tolerable in all 4 studies, and there were few study discontinuations (table 1) – discontinuations due to aes in the ivm arm · phase 2, study 1: 1 (1.9%) · phase 2, study 2: 2 (1.9%) · phase 3, study 1: 7 (1.6%) · phase 3, study 2: 6 (1.3%) • no serious adverse events related to ivm were observed in any of the 4 studies • the incidences of treatment related aes were low, and comparable in both treatment groups – related aes: phase 2, study 1; ivm: 6 (5 subjects, 4.8%); vehicle: 5 (5 subjects, 4.7%) – related aes: phase 2, study 2; ivm: 5 (3 subjects, 5.8%); vehicle: 6 (5 subjects, 10.0%) – related aes: phase 3, study 1; ivm: 24 (19 subjects, 4.2%); vehicle: 25 (18 subjects, 7.8%) – related aes: phase 3, study 2; ivm: 17 (12 subjects, 2.6%); vehicle: 20 (15 subjects 6.5%) introduction • rosacea is a chronic inflammatory disease. • rosacea has traditionally been classified as erythematotelangiectatic (etr), papulopustular (ppr), phymatous, or ocular rosacea. • ppr is characterized by facial papules, pustules, and persistent erythema. • the pathogenesis of ppr is not yet completely understood; however, current studies indicate that underlying causes may include dysregulation of the innate immune system, overgrowth of commensal skin organisms, aberrant neurovascular signaling, and the production of inflammatory mediators in facial skin.1 • ivermectin 1% cream (ivm) is an effective and safe topical therapy approved to treat the inflammatory lesions of rosacea.2 – during the development of ivm, 2 phase 2 and 2 phase 3 vehicle-controlled studies were conducted in more than 1600 subjects. consistent efficacy and safety in four double-blind, vehicle-controlled studies of ivermectin 1% cream in the treatment of moderate to severe papulopustular rosacea linda stein gold, md1; jp york, phd2; jean jacovella, md3 1henry ford medical center, dept. of dermatology, detroit, mi, 2galderma laboratories, l.p., fort worth, tx; 3galderma r&d, sophia antipolis, france soo.p-ma10407-01 summary • in these 4 studies, ivm demonstrated strong efficacy, tolerability, and safety • the data supporting efficacy, tolerability, and safety was replicated with a high level of consistency • the low incidence of aes, good tolerability, and high efficacy make ivm an excellent treatment choice for ppr references 1. holmes, a. d., steinhoff, m. (2016). integrative concepts of rosacea pathophysiology, clinical presentation and new therapeutics. exp dermatol. doi:10.1111/ exd.13143 2. stein l, kircik l, fowler j, et al. efficacy and safety of ivermectin 1% cream in treatment of papulopustular rosacea: results of two randomized, double-blind, vehicle-controlled pivotal studies. j drugs dermatol. 2014 mar;13(3):316-23. ig a su cce ss (p er ce nt o f s ub je cts ) vehicle ivermectin 1% 9.6 32.7 53.8 65.4 8.0 22.0 36.0 42.0 0 10 20 30 40 50 60 70 week 2 week 4 week 8 week 12 (n = 102) *p < .05 * m ea n pe rce nt l es io n re du cti on vehicle ivermectin 1% (n = 102) *p < .05 * **p < .001 ** -23.7 -41.4 -62.6 -69.2 -19.0 -33.1 -44.9 -46.5 -80 -70 -60 -50 -40 -30 -20 -10 0 week 2 week 4 week 8 week 12 ig a su cce ss (p er ce nt o f s ub je cts ) na week 2 week 4 week 8 week 12 (n = 210) **p < .05 *** 17.3 33.7 55.8 2.8 14.2 34.0 0 10 20 30 40 50 60 70 *** *****p < .001 vehicle ivermectin 1% m ea n pe rce nt l es io n re du cti on vehicle na ivermectin 1% (n = 210) na, no assessment *p < .05 * ***p < .001 *** ***-80 -70 -60 -50 -40 -30 -20 -10 0 week 2 week 4 week 8 week 12 42.3 65.2 74.5 32.4 46.2 59.3 ig a su cce ss (p er ce nt o f s ub je cts ) vehicle ivermectin 1% week 2 week 4 week 8 week 12 (n = 683) *p < .05 * 0 10 20 30 40 50 60 70 ***p < .001 *** *** 3.8 10.9 23.1 38.4 2.2 5.6 9.9 11.6 m ea n pe rce nt l es io n re du cti on vehicle ivermectin 1% (n = 683) ***p < .001 *** *** *** *** -80 -70 -60 -50 -40 -30 -20 -10 0 week 2 week 4 week 8 week 12 -27.1 -42.3 -56.9 -64.9 -17.6 -25.7 -34.7 -41.6 ig a su cce ss (p er ce nt o f s ub je cts ) vehicle ivermectin 1% 0 10 20 30 40 50 60 70 week 2 week 4 week 8 week 12 (n = 688) *p < .05 * *** *** 3.5 11.8 27.5 40.1 2.6 5.7 12.2 18.8 ***p < .001 m ea n pe rce nt l es io n re du cti on vehicle ivermectin 1% (n = 688) ***p < .001 *** *** *** ** -80 -70 -60 -50 -40 -30 -20 -10 0 week 2 week 4 week 8 week 12 -26.6 -42.4 -58.7 -65.7 -18.8 -26.1 -36.4 -43.4 **p < .01 figure 1. significant iga success figure 3. representative photographs subject 18171-8129-008 figure 2. mean percent lesion reduction phase 2 phase 3 reason for discontinuation, n (%) study 1 (n = 102) study 2 (n = 210) study 1 (n = 683) study 2 (n = 688) ivermectin 1% enrolled, n = 52 discontinued, n = 3 discontinued (%), 5.8 vehicle enrolled, n = 50 discontinued, n = 7 discontinued (%), 14.0 ivermectin 1% enrolled, n = 104 discontinued, n = 5 discontinued (%), 4.8 vehicle enrolled, n = 106 discontinued, n = 10 discontinued (%), 9.4 ivermectin 1% enrolled, n = 451 discontinued, n = 37 discontinued (%), 8.2 vehicle enrolled, n = 232 discontinued, n = 22 discontinued (%), 9.5 ivermectin 1% enrolled, n = 459 discontinued, n = 30 discontinued (%), 6.5 vehicle enrolled, n = 229 discontinued, n = 21 discontinued (%), 9.2 adverse event 1 (1.9%) 0 2 (1.9%) 2 (1.9%) 7 (1.6%) 4 (1.7%) 6 (1.3%) 4 (1.7%) pregnancy 0 0 0 0 2 (0.4%) 0 1 (0.2%) 0 lack of efficacy 1 (1.9%) 1 (2.0%) 0 0 0 1 (0.4%) 1 (0.2%) 0 withdrawal 1 (1.9%) 5 (10.0%) 1 (1.0%) 5 (4.7%) 18 (4.0%) 7 (3.0%) 9 (2.0%) 8 (3.5%) protocol violation 0 1 (2.0%) 0 1 (0.9%) 2 (0.4%) 1 (0.4%) 4 (0.9%) 0 lost to follow-up 0 0 0 1 (0.9%) 7 (1.6%) 8 (3.4%) 8 (1.7%) 8 (3.5%) other 0 0 2 (1.9%) 1 (0.9%) 1 (0.2%) 1 (0.4%) 1 (0.2%) 1 (0.4%) table 1. subject disposition phase 2, study 1 baseline week 12 phase 2, study 1 phase 2, study 2 phase 2, study 2 phase 3, study 1 phase 3, study 1 phase 3, study 2 phase 3, study 2 iga:4 lesion count: 63 iga:1 lesion count: 2 fc17postergaldermasteingoldconsistentefficacysafetyrosacea.pdf skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 676 brief article atypical targetoid lesions as the presenting sign of myeloid sarcoma eduardo rodriguez, md1, edward visnaw, bs1, frank petr, md2, huma siddiqui, md2 1 university of texas health science center at san antonio, san antonio, tx 2 south texas veterans health care system, san antonio, tx myeloid sarcoma (ms), also known as chloroma or granulocytic sarcoma, is a rare extramedullary solid tumor composed of immature myeloid cells. ms most commonly consists of myeloblasts, with or without features of promyelocytic or neutrophilic maturation, which partially or totally efface the tissue architecture1-2. ms commonly occurs in association with acute myeloid leukemia (aml), affecting 2 to 7% of these patients3-4. ms can also manifest in patients with a history of chromosomal abnormalities, myeloproliferative disorders, myelodysplastic syndrome, or in a blast phase of chronic myeloid leukemia. it may occur before other clinical signs of aml, or alongside other known aml symptoms. ms can also appear in the absence of a primary systemic disease and predate the onset of an underlying hematologic malignancy2. additionally, ms can present as the initial manifestation of relapse in an already treated case or as a therapy related neoplasm1-3. ms has a slight male predominance and can occur at any age. although it can present at any site of the body, the most common reported sites are the skin, lymph nodes, testes, bone, peritoneum, and gastrointestinal tract2-5. cd68-kp1 is the most commonly expressed marker in ms followed by myeloperoxidase (mpo), cd117, cd99, cd68/ pg-m1, lysozyme, cd34, terminal deoxynucleotidyl transferase (tdt), cd56, cd61/linker of activated t lymphocyte/factor viii–related antigen, cd30, glycophorin a, and cd4.2 in this report, we present an unusual appearance of ms presenting with atypical targetoid lesions in a patient undergoing treatment for aml. abstract myeloid sarcoma (ms), also known as chloroma or granulocytic sarcoma, is a rare extramedullary tumor mass that commonly occurs in acute myeloid leukemia (aml). ms may occur before other clinical signs of aml, or alongside other known aml symptoms. ms can also appear in isolation, which makes diagnosis challenging. clinical knowledge about a typical presentation of myeloid sarcoma is limited, given the heterogeneity in the location and size of ms lesions. we describe a patient with a history of aml who developed an eruption of atypical targetoid purpuric lesions. diagnostic workup, including laboratory and histologic specimen from the skin were consistent with ms. ms should be suspected in a patient with a history of myeloproliferative disorder who develops atypical targetoid purpuric papules. introduction skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 677 a 73-year-old male, with a history of aml on azacitidine and enasidenib, presented to the dermatology clinic for evaluation of a purpuric eruption to the arms and legs of 7 to 10 days duration. review of systems were otherwise negative, and the patient had no further complaints at the time. physical exam revealed scattered, round, purpuric macular lesions with a firm, smooth, central, purpuric papule present on the left medial upper arm, right medial thigh, left upper thigh, popliteal fossa, and lower legs/ankle region (figure 1). figure 1. a) round violaceous macules with central papule to left upper arm and b) right anterior thigh respectively. at the time of patient presentation, laboratory evaluation was significant for anemia (hemoglobin 8.4 g/dl [reference range: 13.5-17.5g/dl]), thrombocytopenia (platelets 23 103/μl [reference range: 150400 103/μl]) elevated absolute lymphocytes (lymphocytes, alternate absolute 6.0 103/μl [reference range: 0.9-3.1 103/μl]) monocytes (monocytes 1.6 103/μl [reference range: 0.2-0.8 103/μl]), and blast cell counts (blasts 6.1% [reference range: 0%]). the patient also presented with minimally elevated lactate dehydrogenase (lactate dehydrogenase 279 iu/l [reference range 140-271 iu/l]) and serum uric acid (serum uric acid 5.0mg/dl [2.37.6mg/dl]). a punch biopsy of the right thigh lesion was performed, demonstrating superficial, deep perivascular, and periadnexal mononuclear infiltrate with occasional atypical mitoses. by immunohistochemistry, this infiltrate expressed cd117, cd43, cd4, focal cd34, focal myeloperoxidase, and was negative for cd3 and cd20.(figures 2 & 3) scattered cd68+ cells were present. special stains for organisms were negative. bacterial and fungal tissue cultures were negative. the diagnosis of myeloid sarcoma (ms) was then made. figure 2. punch biopsy, right thigh, h&e; superficial and deep perivascular and periadnexal mononuclear infiltrate with occasional atypical mitoses. figure 3. punch biopsy, right thigh, ihc mpo & cd117. scattered mpo positive staining cells along with numerous cd117 positive staining cells throughout the dermis. case report skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 678 clinical knowledge about a typical presentation of myeloid sarcoma is limited, given the heterogeneity in the location and size of ms lesions. patients with ms are typically younger, have a higher white cell count, and have a greater proportion of aml with monocytic differentiation6. the presenting symptom of ms is typically due to the mass effect of the tumor on nearby tissues or organ dysfunction due to infiltration 2,4. therefore any new cutaneous lesion in a patient with aml should raise suspicion for ms. cutaneous ms typically presents as multiple papules, plaques, or nodules4. the most common region involved is the torso, although head, neck, and extremities are also commonly involved7. diagnosing ms depends on a combination of clinical features, radiological evidence, and in most cases tissue biopsy1. most common imaging modalities include ct and mri to exclude differential diagnoses such as abscesses and hematomas. mri is preferred in the setting of musculoskeletal lesions and involvement of the central nervous system. pet-ct has also been reported to be helpful in localization of tumors and detection of synchronous lesions.6 ms has been reported to demonstrate sensitivity to different therapies such as chemotherapy, radiation, and hematopoietic stem cell transplantation. optimal treatments for ms have not been established due to lack of randomized controlled trials, however, chemotherapy is commonly the initial therapy. other treatment methods that have been reported include local therapies such as surgery, radiotherapy, or a combination of both. however, retrospective series have demonstrated a high rate of progression to aml in patients with isolated ms treated with local therapies only. no controlled trials evaluating the role of allogenic hematopoietic stem cell transplantation in patients with isolated ms have been performed but retrospective studies have demonstrated encouraging results.6 ms prognosis can be variable depending on the different backgrounds of ms formation but it is typically accepted to be poor. untreated ms commonly transforms to aml over a 10– 12-month period.6, 8-10 patients with isolated ms involvement of the pelvis, eyes, gonads, genitourinary organs, and gastrointestinal mucosa had reported better outcomes as compared to those with involvement of primary soft tissue sites, nervous system, lymphatic, and hematopoietic tissues. in prior studies, patients with ms had a greater 3-year survival rate as compared to patients with non-ms aml.11 this case represents an atypical presentation of myeloid sarcoma in a patient with known acute myeloid leukemia. despite multiple reports in the literature, the authors have found no other reported cases of ms presenting with atypical targetoid lesions.1213 the atypical targetoid presentation in this patient emphasizes the importance of having a high index of suspicion for ms when a patient with a history of a myeloproliferative disorder presents with any new suspicious cutaneous lesions or eruptions. a thorough work-up should be performed when patients present with new widespread cutaneous lesions, especially on patients who have current or prior history of any hematologic malignancies. a representative lesion biopsy with immunohistochemistry evaluation for assessment of features consistent with ms should be highly considered on these patients. discussion conclusion skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 679 conflict of interest disclosures: none funding: none corresponding author: eduardo rodriguez, md 7979 wurzbach road san antonio, texas 78229 phone: 210-450-9840 email: rodrigueze25@uthscsa.edu references: 1. meyer h, beimler m, borte g, pönisch w, surov a. radiological and clinical patterns of myeloid sarcoma. radiology and oncology. 2019;53(2):213-218. doi: 10.2478/raon-20190014. 2. campidelli c, agostinelli c, stitson r, pileri sa. myeloid sarcoma: extramedullary manifestation of myeloid disorders. american journal of clinical pathology. 2009;132(3):426 3. kaur v, swami a, alapat d, et al. clinical characteristics, molecular profile and outcomes of myeloid sarcoma: a single institution experience over 13 years. hematology. 2018;23(1):17-24. doi:10.1080/10245332.2017.1333275 4. neiman rs, barcos m, berard c, et al. granulocytic sarcoma: a clinicopathologic study of 61 biopsied cases. cancer. 48(6):1426-1437. doi:10.1002/10970142(19810915)48:6<1426::aidcncr2820480626>3.0.co;2-g 5. kawamoto k, takizawa j, sone h, miyoshi h, yoshida n, ohshima k. clinicopathological, cytogenetic, and prognostic analysis of 131 myeloid sarcoma patients. american journal of surgical pathology. 40(11):1473-1483. doi:10.1097/pas.0000000000000727 6. almond lm, charalampakis m, ford sj, gourevitch d, desai a. myeloid sarcoma: presentation, diagnosis, and treatment. clinical lymphoma, myeloma & leukemia. 2017;17(5):263-267. doi: 10.1016/j.clml.2017.02.027. 7. klco jm, welch js, nguyen tt, et al. state of the art in myeloid sarcoma. international journal of laboratory hematology. 2011;33(6):555-565. doi: 10.1111/j.1751553x.2011.01361.x 8. katagiri t, ushiki t, masuko m, et al. successful 5-azacytidine treatment of myeloid sarcoma and leukemia cutis associated with myelodysplastic syndrome: a case report and literature review. medicine. 2017;96(36):e7975. doi:10.1097/md.0000000000007975 9. antic d, elezovic i, milic n, et al. is there a “gold” standard treatment for patients with isolated myeloid sarcoma? biomedicine & pharmacotherapy. 2013;67(1):72-77. doi:10.1016/j.biopha.2012.10.014 10. kawamoto k, miyoshi h, yoshida n, takizawa j, sone h, ohshima k. clinicopathological, cytogenetic, and prognostic analysis of 131 myeloid sarcoma patients. the american journal of surgical pathology. 2016;40(11):1473-1483. accessed august 19, 2020. http://search.ebscohost.com.libproxy.uthscsa .edu/login.aspx?direct=true&db=cmedm&an =27631510&site=eds-live&scope=site 11. movassaghian, m., brunner, a. m., blonquist, t. m., sadrzadeh, h., bhatia, a., perry, a. m., attar, e. c., amrein, p. c., ballen, k. k., neuberg, d. s., & fathi, a. t. (2014). presentation and outcomes among patients with isolated myeloid sarcoma: a surveillance, epidemiology, and end results database analysis. leukemia & lymphoma, 56(6), 1698–1703. https://doi.org/10.3109/10428194.2014.9630 80 12. niiyama s, amoh y, watarai a, katsuoka k, mukai h. cutaneous myeloid sarcoma presenting as grey pigmented macules. acta dermato-venereologica. 2012;92(6):629-630. doi:10.2340/00015555-1312 13. hurley my, ghahramani gk, frisch s, et al. cutaneous myeloid sarcoma: natural history and biology of an uncommon manifestation of acute myeloid leukemia. acta dermatovenereologica. 2013;93(3):319-324. doi:10.2340/00015555-1458 mailto:rodrigueze25@uthscsa.edu skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 656 research letter virtual medical student dermatologic surgery workshop increases confidence in suturing and skin biopsy skills in the era of covid19 emily dando, md1, angela guerrero, md1, mary-katharine collins, md1, alaina j. james, md, phd1 1 department of dermatology, university of pittsburgh medical center, pittsburgh, pa medical students benefit from early and repeated practice with surgical skills. students who participate in procedure training demonstrate increased confidence and ability when applying these skills to patients.1 in the era of covid-19, many preclinical medical school curricula have transitioned to remote learning, which may reduce critical early exposure to basic procedures. our group developed a dermatologic surgery curriculum for secondyear medical students in order to address the need for continued procedural education in the remote learning setting. we evaluated whether this asynchronous, virtual procedural workshop affected their level of confidence (loc) in their ability to perform these skills. abstract background: during the covid-19 pandemic, many pre-clinical medical school courses were conducted virtually. in order to increase exposure to basic procedures in the remote learning setting, our group developed a virtual dermatologic surgery workshop. methods: all 147 second-year medical students at the university of pittsburgh watched 70 minutes of pre-recorded lectures that introduced suturing, skin biopsies, and other dermatologic procedures. each student was provided with a suturing kit to remotely practice the following skills: simple interrupted suture, simple running suture, horizontal mattress suture, vertical mattress suture, running subcuticular suture, shave biopsy, and punch biopsy. preand post-workshop surveys were distributed to the students and paired using a randomized de-identified number. results: 117 (80%) students completed the pre-survey and 71 (48%) completed the post-survey. 61 (41%) responses were paired. the average baseline level of confidence ranged from 1.0 on a 10point scale for subcuticular running suture to 2.4 for simple interrupted suture. the average level of confidence increased after the workshop for each skill, ranging from 3.7 for subcuticular running suture to 8.0 for instrument tie. in the paired responses, the average level of confidence increased significantly for each skill by an average of 5.5 points (sd=1.1, p<.001). conclusions: a virtual, asynchronous dermatologic surgery workshop significantly increases medical student confidence in their ability to perform suturing and skin biopsies. introduction methods skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 657 in this irb-approved study (study20110280), all second-year medical students at the university of pittsburgh were invited to complete preand post-workshop surveys on qualtrics. students watched 70 minutes of prerecorded lectures that introduced suturing, skin biopsies, excisions, mohs micrographic surgery, cryotherapy, electrodessication, and cosmetics (https://pitt.hosted.panopto.com/panopto/pa ges/sessions/list.aspx?folderid=69f36939668a-4742-a9fe-acf9011a49b5). each student was provided with a suturing pad and surgical tools to remotely practice and submit photos of the following skills: simple interrupted suture, simple running suture, horizontal mattress suture, vertical mattress suture, running subcuticular suture, shave biopsy, and punch biopsy (figure 1). a twohour virtual office hour session was held by the senior author on zoom to allow students to ask questions about the workshop. figure 1: example student submission of suturing and biopsy workshop. 1 = simple interrupted suture; 2 = simple running suture; 3 = horizontal mattress suture; 4 = vertical mattress suture; 5 = subcuticular running suture; 6 = shave biopsy; 7 = punch biopsy surveys were distributed to 147 second-year medical students. a randomized deidentified number paired individual responses which were compared using a paired t-test. 117 (80%) students completed the pre-survey and 71 (48%) completed the post-survey, including 61 (41%) paired responses. most students had limited prior suturing exposure – 66 (56%) had no suturing education through textbooks, lectures or videos, and 47 (40%) had five or fewer hours. 52 (44%) had no hands-on suturing experience, and 56 (48%) had five or fewer hours. 18 (15%) of the pre-survey respondents held clinical positions prior to medical school. the average baseline loc in each skill ranged from 1.0 for subcuticular running suture to 2.4 for simple interrupted suture on a 10-point likert scale (table 1). after the workshop, the average loc increased for each skill, ranging from 3.7 for subcuticular running suture to 8.0 for instrument tie. loc increased significantly for each skill in the 61 paired responses by an average of 5.5 points (sd = 1.1, p<.001). students reported difficulty with the subcuticular running suture due to tearing of the suture pad. most students (65, 92%) watched all of the workshop videos in their entirety. all students strongly agreed (57, 80%) or agreed (14, 20%) that they learned from the workshop and strongly agreed (64, 90%) or agreed (7, 10%) that it should be offered again next year. one student attended the virtual office hour session to discuss suturing technique, and several additional students emailed the instructors with questions. results skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 658 table 1. average level of confidence in skills before and after virtual suturing and biopsy workshop skill level of confidence in skill, mean (sd)* change in level of confidence in skill in paired responses (n=61) before works hop (n=117 ) after works hop (n=71 ) mean (sd) p† instrument tie 2.3 (2.9) 8.0 (1.9) 5.8 (2.8) <.001 simple interrupted suture 2.4 (3.0) 7.9 (1.9) 5.6 (2.8) <.001 simple running suture 1.9 (2.8) 7.2 (2.1) 5.4 (2.6) <.001 vertical mattress suture 1.2 (2.4) 6.8 (2.0) 5.7 (2.6) <.001 horizontal mattress suture 1.3 (2.4) 6.9 (2.1) 5.9 (2.5) <.001 subcuticul ar running suture 1.0 (2.2) 3.7 (2.5) 2.8 (2.2)‡ <.001 shave biopsy 1.5 (2.5) 7.6 (2.1) 6.6 (2.4) <.001 punch biopsy 1.6 (2.7) 7.6 (2.0) 6.4 (2.5) <.001 *on a 10-point likert scale where 0=no confidence in ability to perform task and 10=full confidence in ability to perform task †paired t-test ‡students reported difficulty with the subcuticular running suture due to tearing of the suture pad. after participating in a virtual suturing and biopsy workshop, second-year medical students reported significantly increased confidence in their ability to perform the reviewed skills. prior to our workshop, almost all students had no or little suturing exposure. all students learned from the workshop and felt that it should be offered again next year. our students were more likely to utilize email rather than virtual office hours to discuss questions with their instructors. participation bias is a potential limitation. moving forward, this workshop may be adapted to a flipped classroom model to maximize the in-person learning experience.2 abbreviations: loc = level of confidence acknowledgements: we thank the university of pittsburgh school of medicine office of medical education for providing the suturing kits and the university of pittsburgh medical center department of dermatology for providing the biopsy tools. conflict of interest disclosures: none funding: none corresponding author: emily dando, md educational chief resident department of dermatology university of pittsburgh medical center 3601 fifth avenue, 5th floor pittsburgh, pa 15213 phone: (412) 647-4200 email: dandoee3@upmc.edu references: 1. manning ep, mishall pl, weidmann md, et al. early and prolonged opportunities to practice suturing increases medical student comfort with suturing during clerkships: suturing during conclusion mailto:dandoee3@upmc.edu skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 659 cadaver dissection. anat sci educ. nov 2018;11(6):605-612. doi:10.1002/ase.1785 2. liu kj, tkachenko e, waldman a, et al. a videobased, flipped classroom, simulation curriculum for dermatologic surgery: a prospective, multiinstitution study. j am acad dermatol. dec 2019;81(6):1271-1276. doi:10.1016/j.jaad.2019.03.078 tapinarof cream 1% once daily for plaque psoriasis: long-term extension trial of a novel therapeutic aryl hydrocarbon receptor modulating agent bruce strober,1 linda stein gold,2 robert bissonnette,3 april armstrong,4 andrew blauvelt,5 leon kircik,6,7 philip m. brown,8 anna m. tallman,8 mark lebwohl7 1yale university, new haven & central connecticut dermatology research, cromwell, ct, usa, 2henry ford health system, detroit, mi, usa, 3innovaderm research inc., montreal, qc, canada, 4keck school of medicine at university of southern california, los angeles, ca, usa, 5oregon medical research center, portland, or, usa, 6skin sciences pllc, louisville, ky, usa, 7icahn school of medicine at mount sinai, new york, ny, usa, 8dermavant sciences, inc., morrisville, nc, usa synopsis ■ in two 12-week pivotal phase 3 trials, psoaring 1 (nct03956355) and psoaring 2 (nct03983980), tapinarof cream 1% once daily (qd) demonstrated highly statistically and clinically significant efficacy versus vehicle and was well tolerated in adults with mild to severe plaque psoriasis1 ■ tapinarof cream 1% qd also demonstrated maintenance of efficacy for 4 weeks after treatment discontinuation in a 12-week phase 2b trial, warranting further investigation of a potential remittive effect2 objective ■ to present the results of psoaring 3 (nct04053387), a long-term extension trial designed to assess the safety, efficacy, durability of response, tolerability, and duration of remittive effect of tapinarof during repeated intermittent treatment, based on patient physician global assessment (pga) score methods study design ■ patients completing psoaring 1 and psoaring 2 were eligible to enroll in psoaring 3 for 40 weeks of open-label treatment with tapinarof cream 1% qd, followed by four weeks of follow-up (figure 1) ■ in psoaring 3, patients were treated with tapinarof 1% qd based on individual patient pga score: – patients who entered with a pga score of ≥1 received tapinarof 1% qd until complete disease clearance was achieved, defined as a pga score of 0 – patients who entered with, or achieved, a pga score of 0 discontinued treatment and were observed for remittive effect, defined as maintenance of a pga score of 0 (clear) or 1 (almost clear), while off therapy – if disease worsening occurred, defined as a pga score ≥2, tapinarof 1% qd was started and continued until a pga score of 0 (clear) was achieved figure 1. psoaring 3 study design pga, physician global assessment; qd, once daily. endpoints and statistical analysis ■ safety: adverse events (aes), laboratory values, vital signs and physical exams ■ efficacy: – complete disease clearance: proportion of patients achieving pga of 0 (clear) – remittive effect: duration of efficacy maintenance defined as pga of 0 (clear) or 1 (almost clear) while off therapy after achieving complete disease clearance (pga=0) – response: proportion of patients who entered the trial with a pga≥2 and achieved a pga of 0 (clear) or 1 (almost clear) at least once during the trial – durability of response (absence of tachyphylaxis): maintenance of efficacy while on treatment, defined as the proportion of patients who achieved a pga score of 0 or 1 at least once during the trial, and trends in psoriasis area and severity index (pasi) score and percentage of body surface area (%bsa) affected over time ■ tolerability: local tolerability using a patient-reported 5-point scale for burning/ stinging and itching, and an investigator-assessed 5-point scale for dryness, erythema, and peeling ■ efficacy analyses used observed case (oc) or last observation carried forward (locf) analysis that were based on the intention-to-treat (itt) population results baseline patient demographics and disease characteristics ■ overall, 763 (91.6%) of eligible patients completing psoaring 1 and psoaring 2 opted to enroll in psoaring 3 ■ patient demographics and disease characteristics are summarized in table 1, including baseline values by prior treatment arm in the pivotal trials ■ patients previously randomized to tapinarof 1% qd (tapinarof→tapinarof) had lower baseline disease scores compared to the vehicle qd (vehicle→tapinarof) group, reflecting the significant efficacy of tapinarof in the pivotal studies – 14.6% (74/508) versus 2.0% (5/255) of patients had complete disease clearance (pga of 0), and 65.2% (331/508) versus 30.2% (77/255) of patients had a pga score of 1 (almost clear) or 2 (mild) in the tapinarof qd pivotal group (tapinarof→tapinarof) versus the vehicle qd pivotal group, (vehicle→tapinarof) respectively table 1. psoaring 3 baseline patient demographics and disease characteristics overall (n=763) tapinarof → tapinarof* (n=508) vehicle → tapinarof* (n=255) age, years, mean (sd) 50.7 (12.88) 50.5 (12.87) 51.0 (12.93) male, n (%) 448 (58.7) 304 (59.8) 144 (56.5) weight, kg, mean (sd) 92.4 (23.90) 92.6 (25.13) 92.1 (21.28) bmi, kg/m2, mean (sd) 31.7 (7.71) 31.6 (8.07) 31.8 (6.97) pga, n (%)† 0 – clear 79 (10.4) 74 (14.6) 5 (2.0) 1 – almost clear 161 (21.1) 144 (28.3) 17 (6.7) 2 – mild 247 (32.4) 187 (36.8) 60 (23.5) 3 – moderate 249 (32.6) 93 (18.3) 156 (61.2) 4 – severe 23 (3.0) 7 (1.4) 16 (6.3) pasi, mean (sd)† 4.8 (4.72) 3.3 (3.53) 7.7 (5.39) bsa affected, %, mean (sd)† 4.7 (5.60) 3.3 (4.74) 7.3 (6.21) *tapinarof→tapinarof: patients previously assigned to tapinarof in the pivotal trials who enrolled in psoaring 3; vehicle→tapinarof: patients previously assigned to vehicle in the pivotal trials who enrolled in psoaring 3. †four patients (3 previously assigned to tapinarof, 1 previously assigned to vehicle) did not have a baseline pga, pasi, and bsa value and are listed as missing. itt population. bmi, body mass index; bsa, body surface area; itt, intention-to-treat; pasi, psoriasis area and severity index; pga, physician global assessment, sd, standard deviation. complete disease clearance (pga of 0) ■ overall, 40.9% (312/763) of patients achieved complete disease clearance at least once during the study; this included 233 patients who entered the study with a pga of ≥1, and 79 patients who entered with a pga of 0 (figure 2a) response among patients entering with a pga of ≥2 ■ overall, 58.2% (302/519) of patients entering the study with a pga of ≥2 achieved a pga of 0 (clear) or 1 (almost clear) at least once during the study (figure 2b) figure 2. complete disease clearance (pga=0) and response rates (pga=0 or 1) *including patients who entered with pga=0 (n=79) and patients entering with pga ≥1 who achieved pga=0 at least once during the study (n=233) itt population, oc. itt, intention-to-treat; oc, observed cases; pga, physician global assessment. remittive effect: time to first worsening among patients entering with a pga of 0 (n=79) ■ the duration of remittive effect (kaplan-meier estimated median, 95% confidence interval [ci]) while off therapy for patients who entered the study with a pga of 0 (clear) was 115.0 (95% ci; 85.0-168.0) days (figure 3) figure 3. duration of remittive effect among patients entering with a pga of 0: maintenance of a pga of 0 (clear) or 1 (almost clear) while off therapy itt population, oc. itt, intention-to-treat; oc, observed cases; pga, physician global assessment. total duration of remittive effect among patients entering with, or achieving, a pga of 0 (n=312) ■ the total duration of remittive effect (mean, standard deviation [sd]) while off therapy was 130.1 (89.4) days, a possible underestimate as study end, not disease worsening, truncated the duration for some patients durability of response ■ durability of response of up to 52 weeks was demonstrated with intermittent use of tapinarof 1% qd, indicating no observation of tachyphylaxis (defined as loss of response) while on therapy (figure 4) ■ patients previously treated with vehicle in the 12-week pivotal trials achieved similar responses to patients previously treated with tapinarof (figure 4) figure 4. durability of response (no tachyphylaxis while on therapy) based on proportion of patients achieving a pga score of 0 (clear) or 1 (almost clear) at least once during the study *tapinarof→tapinarof: patients previously assigned to tapinarof in the pivotal trials who enrolled in psoaring 3; vehicle→tapinarof: patients previously assigned to vehicle in the pivotal trials who enrolled in psoaring 3. itt population, locf. itt, intention-to-treat; locf, last observation carried forward; pga, physician global assessment. safety ■ as previously reported, there were no new safety signals during the long-term safety trial3 and aes were consistent with previous studies1,2 ■ the most common treatment-emergent aes included folliculitis, contact dermatitis, and upper respiratory tract infection ■ study discontinuation due to folliculitis and contact dermatitis was low, 1.2% (9/763) and 1.4% (11/763), respectively, and similar to the rates observed in psoaring 1 and psoaring 21 conclusions ■ tapinarof cream 1% qd provided sustained improvement in efficacy endpoints with long-term intermittent use ■ a high rate of complete disease clearance (40.9%) and a remittive effect of approximately 4 months off therapy was demonstrated with tapinarof 1% qd, with no tachyphylaxis observed for up to 52 weeks ■ tapinarof cream 1% qd was well tolerated with long-term use and had a safety profile consistent with previous studies1,2 references 1. lebwohl m, et al. skin. 2020;4(6):s75; 2. robbins k et al. j am acad dermatol. 2019;80:714–721; 3. strober b, et al. innovations in dermatology virtual spring conference 2021, poster presentation, march 16–20, 2021. acknowledgments this study was funded by dermavant sciences, inc. the authors thank the participating investigators, patients and their families, and colleagues involved in the conduct of the study. b.s. has served as an honorary consultant/speaker/scientific director/investigator for abbvie, almirall, amgen, arcutis, arena, aristea, boehringer ingelheim, bristol-myers-squibb, cara, celgene, corrona psoriasis registry, dermavant sciences inc., dermira, equillium, janssen, leo, eli lilly, meiji seika pharma, mindera, novartis, pfizer, glaxosmithkline, ucb pharma, sun pharma, ortho dermatologics, regeneron, sanofi-genzyme. l.s.g has served as a consultant, and/or has received payment for the development of educational presentations, and/or has received grants from arcutis, amgen, bristol myers squibb, dermavant sciences, inc., eli lilly, leo pharma, ortho dermatologic and ucb biopharma. r.b. has served as a consultant/advisory board member/ speaker/investigator, and/or receives honoraria/grant from almirall, amgen, anaptysbio, arcutis, arena pharma, aristea, asana biosciences, bausch health, bellus health, bluefin biomedicine, boehringer-ingelheim, bristol-myers squibb, cara, dermavant sciences inc., eli lilly, emd serono, escalier, evidera, galderma, gsk, inmagene bio, incyte, janssen, kiniksa, kyowa kirin, leo pharma, nimbus, novan, pfizer, ralexar, rapt, regeneron, respivant, sanofi genzyme, sienna, target rwe, ucb. r.b. is an employee and shareholder of innovaderm research. am is a research investigator and/or scientific advisor to abbvie, bi, bms, epi, incyte, leo, ucb, janssen, lilly, novartis, ortho dermatologics, sun, dermavant sciences inc., dermira, sanofi, regeneron, pfizer, modmed. ab has served as a scientific adviser and/ or clinical study investigator for abbvie, abcentra, aligos, almirall, amgen, arcutis, arena, aslan, athenex, boehringer ingelheim, bristol-myers squibb, dermavant, eli lilly and company, evommune, forte, galderma, incyte, janssen, landos, leo, novartis, pfizer, rapt, regeneron, sanofi genzyme, sun pharma, and ucb pharma. l.k. has served as a consultant/speaker/investigator/advisory board member for abbott laboratories, abbvie, ablynx, aclaris, acambis, allergan, inc., almirall, amgen, inc., anacor pharmaceuticals, anaptys, arcutis, arena, assos pharma, astellas pharma us, inc., asubio, bausch health, berlex laboratories (bayer healthcare pharmaceuticals), biogen-idec, biolife, biopelle, bms, boehringer-ingleheim, breckinridge pharma, cassiopea, centocor, inc., cellceutix, cipher, coherus, colbar, combinatrix, connetics corporation, coria, dermavant sciences inc, dermira, dermik laboratories, dow pharmaceutical sciences, inc., dr. reddy’s lab, dusa , embil pharmaceuticals, eli lilly, eos, exeltis, ferndale laboratories, inc., foamix, ferrer, galderma, genentech, inc., glaxosmithkline, plc, glenmark, health point, ltd, idera, incyte, intendis, innocutis, innovail, isdin, johnson & johnson, kyowakirin, laboratory skin care inc., leo pharma, l’oreal, 3m, maruho, medical international technologies, merck, medicis pharmaceutical corp., merz, nano bio, novartis ag, noven pharmaceuticals, nucryst pharmaceuticals corp, obagi, onset, orthoneutrogena, pediapharma, pfizer, promius, puracap, pharmaderm, qlt, inc, quinnova, quatrix, regeneron, sanofi, serono (merck serono international sa), skinmedica, inc., stiefel laboratories, inc., sun pharma, taro, tolerrx, triax, ucb, valeant pharmaceuticals intl, warner-chilcott, xenoport, zage. p.m.b and a.n.t. are employees of dermavant sciences inc., with stock options. m.l. has received grants, and/or is a consultant for abbvie, amgen, aditum bio, almirall, altrubio inc., anaptysbio, arcutis, aristea therapeutics, arrive technologies, avotres, biomx, boehringer ingelheim, bristol-myers squibb, cara therapeutics, castle biosciences, corrona, dermavant sciences, dr. reddy’s laboratories, eli lilly, evelo biosciences, evommune, inc., facilitation of international dermatology education, forte biosciences, foundation for research and education in dermatology, helsinn therapeutics, hexima ltd., incyte, janssen research & development, leo pharma, llc, meiji seika pharma, mindera, ortho dermatologics, pfizer, regeneron, seanergy, ucb, inc., verrica. editorial and medical writing support under the guidance of the authors was provided by apothecom, uk, and was funded by dermavant sciences, inc. in accordance with good publication practice (gpp3) guidelines (ann intern med. 2015;163:461–464). contact dr bruce strober at brucestrober30@me.com with questions or comments. long-term open-label extension (40 weeks) follow-up (4 weeks) double-blind treatment (12 weeks) off treatment off treatment pga=0 (n=79) pga=0 stop treatment pga≥2 re-start pga≥1 (n=680) tapinarof 1% qd pivotal (n=508) tapinarof 1% qd vehicle qd pivotal (n=255) a. complete disease clearance (pga=0) p ro p o rt io n o f p a ti e n ts ( % ) 60 50 40 30 20 10 0 overall (n=763) overall (n=519) 40.9%* b. response (pga=0 or 1 among patients entering with a pga≥2) p ro p o rt io n o f p a ti e n ts ( % ) 60 70 50 40 30 20 10 0 58.2% overall tapinarof→tapinarof* vehicle→tapinarof* p ro p o rt io n o f p a ti e n ts , % 0 10 20 30 40 50 60 70 0 4 8 12 16 20 week number of subjects overall tapinarof→tapinarof* vehicle→tapinarof* 240 218 22 273 216 57 330 243 87 334 233 101 336 239 97 358 250 108 346 236 110 336 230 106 339 233 106 340 225 115 330 224 106 24 28 32 36 40 overall (n=79) p ro b a b il it y o f d is e a se w o rs e n in g 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 number of subjects overall 0 79 76 58 48 44 33 29 23 19 17 17 17 15 0 25 50 75 median time to pga≥2 115 days 100 125 150 175 time (days) 200 225 250 275 300 325 mean percentage improvement in psoriasis area and severity index (pasi) response and absolute pasi through 5 years of continuous treatment with guselkumab in voyage 1 joseph f. merola1, luis puig2, megan miller3, yin you3, yaung-kaung shen3, ya-wen yang4, andrew blauvelt5 1harvard medical school, brigham and women’s hospital, boston, ma, usa; 2hospital de la santa creu i sant pau, autonomous university of barcelona, barcelona, spain; 3janssen research & development, llc, spring house, pa, usa; 4immunology global medical affairs, janssen pharmaceutical companies of johnson & johnson, horsham, pa, usa; 5oregon medical research center, portland, or, usa background/objective methods conclusions this poster was supported by janssen research and development, llc • originally presented at eadv’s 30th congress, virtual, september 29-october 2, 2021. presented at the winter clinical dermatology conference hawaii® (wc22), 14th-19th jan 2022. • voyage 1, a 5-year, phase 3, randomized, doubleblinded, placebo (pbo)and active comparatorcontrolled study compared guselkumab (gus), a fully human anti-interleukin-23 monoclonal antibody, with pbo and adalimumab (ada) in patients with moderate to severe plaque psoriasis1 • the objective of this analysis was to assess percentage improvement in psoriasis area and severity index (pasi) as well as absolute pasi response through 5 years of continuous gus treatment • continuous treatment with gus provided robust and durable skin responses based on percentage improvement in pasi as well as absolute pasi through 5 years • no new safety concerns were identified through week 264 results baseline demographics, disease characteristics, and prior psoriasis treatments were generally similar across treatment groups (table 1) mean percentage improvement from baseline in pasi was 93% or greater at each time point in the gus group from week 52 through week 252. a similar response was observed in the ada→gus group over time. (figure 1) median absolute pasi (iqr) was 0.10 (0.00; 1.65) in the gus group (n=468) and 2.00 (0.20; 6.00) in the ada→gus group (n=279) at week 52; and 0.00 (0.00; 1.20) in the gus group (n=391) and 0.00 (0.00; 1.60) in the ada→gus group (n=246) at week 252 • median percentage improvement from baseline in pasi over time is shown in figure 2 • no new safety signals were identified through week 264 (table 2) error bars represent q1 and q3. *includes patients randomized to gus at baseline and those randomized to pbo at baseline who crossed over to gus at week 16. ada=adalimumab; gus=guselkumab; iqr=interquartile range; pasi=psoriasis area and severity index; pbo=placebo references 1. blauvelt a, et al. j am acad dermatol. 2017;76(3):405-417. figure 3. median absolute pasi (iqr) through week 252 disclosures joseph f. merola has served as a consultant and/or investigator for abbvie, arena, biogen, bristol myers squibb, dermavant, eli lilly, janssen, novartis, pfizer, sun pharma, and ucb. luis puig has served as a speaker/consultant/advisory board member for and/or received research funding from abbvie, almirall, amgen, baxalta, biogen, boehringer ingelheim, bristol myers squibb, celgene, fresenius-kabi, gebro, janssen, js biocad, leo pharma, lilly, merck-serono, msd, mylan, novartis, pfizer, regeneron, roche, sandoz, samsung-bioepis, sanofi, and ucb. megan miller, yin you and yaung-kaung shen are employees of janssen research and development, llc, and ya-wen yang is an employee of immunology global medical affairs, janssen pharmaceutical companies of johnson & johnson; employees may own stock in johnson & johnson, of which janssen is a subsidiary. andrew blauvelt has served as a scientific advisor and/or clinical study investigator for abbvie, abcentra, aligos, almirall, amgen, arcutis, arena, aslan, athenex, boehringer ingelheim, bristol-myers squibb, dermavant, ecor1, eli lilly and company, evommune, forte, galderma, incyte, janssen, landos, leo pharma, novartis, pfizer, rapt, regeneron, sanofi genzyme, sun pharmaceutical, ucb, and vibliome. • in voyage 1, 837 patients were randomized in a 2:1:2 ratio to receive: o gus 100 mg administered by subcutaneous (sc) injection at weeks 0 and 4, then every 8 weeks (q8w) (n=329) o pbo at weeks 0, 4, and 12, followed by gus 100 mg sc at weeks 16 and 20, then q8w (n=174) o ada 80 mg sc at week 0, 40 mg at week 1, then 40 mg every 2 weeks through week 47, followed by gus 100 mg at week 52, then q8w (n=334) • patients entered open-label gus treatment during weeks 52-252 • analyses were performed to summarize the following through week 252: o mean and median percentage improvement from baseline in pasi o median absolute pasi with interquartile range (iqr) • in addition to patients randomized to gus, pbo, and ada at baseline, treatment groups analyzed: o gus group: includes patients randomized to gus at baseline and those randomized to pbo at baseline who crossed over to gus at week 16 o ada crossover to gus (ada→gus) group: includes patients randomized to ada at baseline who crossed over to gus at week 52 o combined gus group: includes the gus group and ada→gus group, as defined above • through week 48, last observation carried forward (locf) was applied for all missing data regardless of the reason after application of treatment failure rules (tfr), whereupon zero was assigned to pasi percent improvement and baseline pasi was used for those who discontinued study agent due to lack of efficacy or worsening of psoriasis, or used a protocolprohibited psoriasis treatment. starting at week 52, analyses were performed using observed data after applying tfr. • safety was evaluated through week 264 table 2. adverse events through week 264 gus* ada→gus** combined gus treated patients, n 494 280 774 average duration of follow-up, weeks 226.4 199.0 216.5 ≥1 ae 442 (89.5) 237 (84.6) 679 (87.7) discontinued due to ≥1 ae 33 (6.7) 14 (5.0) 47 (6.1) ≥1 sae 95 (19.2) 32 (11.4) 127 (16.4) infections 357 (72.3) 190 (67.9) 547 (70.7) requiring antibiotics 188 (38.1) 101 (36.1) 289 (37.3) serious infections 18 (3.6) 4 (1.4) 22 (2.8) malignancies other than nmsc‡ 15 (3.0) 3 (1.1) 18 (2.3) nmsc 9 (1.8) 4 (1.4) 13 (1.7) mace 6 (1.2) 2 (0.7) 8 (1.0) suicidal ideation and behavior 3 (0.6) 2 (0.7) 5 (0.6) deaths 4 (0.8) 1 (0.4) 5 (0.6) data shown are n (%), unless otherwise indicated. *includes patients randomized to gus at baseline and to pbo who crossed over to gus at week 16. **includes patients randomized to ada at baseline who crossed over to gus at week 52. ‡includes 4 colorectal, 3 breast, 2 each of head and neck, melanoma, and prostate, and 1 each of bladder, brain, lymphoma, sarcoma, and stomach. ae=adverse event; ada=adalimumab; gus=guselkumab; mace=major adverse cardiovascular event; nmsc=nonmelanoma skin cancer; sae=serious adverse event table 1. baseline demographics and disease characteristics pbo gus ada total randomized patients, n 174 329 334 837 age [years] 44.9 ± 12.9 43.9 ± 12.7 42.9 ± 12.6 43.7 ± 12.7 male, n (%) 119 (68.4) 240 (72.9) 249 (74.6) 608 (72.6) body mass index (kg/m2) 28.9 ± 6.9 29.7 ± 6.2 29.8 ± 6.5 29.6 ± 6.5 body surface area (%) 25.8 ± 15.9 28.3 ± 17.1 28.6 ± 16.7 27.9 ± 16.7 pasi (0-72) 20.4 ± 8.7 22.1 ± 9.5 22.4 ± 9.0 21.9 ± 9.2 iga score (moderate), % 75.3 76.6 72.2 74.6 iga score (severe), % 24.7 23.4 26.9 25.1 duration of psoriasis [years] 17.6 ± 12.4 17.9 ± 12.3 17.0 ± 11.3 17.5 ± 11.9 patients with psoriatic arthritis, n (%) 30 (17.2) 64 (19.5) 62 (18.6) 156 (18.6) prior psoriasis treatments, n (%) topical agents 154 (88.5) 299 (90.9) 309 (92.8) 762 (91.1) phototherapy (puva or uvb) 86 (49.4) 188 (57.3) 180 (53.9) 454 (54.3) non-biologic systemics 92 (52.9) 210 (63.8) 215 (64.4) 517 (61.8) biologics 34 (19.5) 71 (21.6) 70 (21.0) 175 (20.9) data shown are mean ±sd, unless otherwise indicated. ada=adalimumab; gus=guselkumab; iga=investigator’s global assessment; pasi=psoriasis area and severity index; pbo=placebo; puva=psoralen and utraviolet a; sd=standard deviation; uvb=ultraviolet b *includes patients randomized to gus at baseline and those randomized to pbo at baseline who crossed over to gus at week 16. ada=adalimumab; gus=guselkumab; pasi=psoriasis area and severity index; pbo=placebo figure 1. mean percent improvement from baseline in pasi through week 252 0 20 40 60 80 100 0 4 8 12 16 20 24 28 32 36 40 44 48 52 60 68 76 84 92 100 108 116 124 132 140 148 156 164 172 180 188 196 204 212 220 228 236 244 252 m e a n p e rc e n t im p ro ve m e n t f ro m b a s e lin e gus pbo pbogus gus* adagusada weeks 94.293.1 93.7 94.1 73.4 93.3 93.9 94.9 93.0 93.1 269 448 432468 165 329 334 275 256 411 246 391 92.9 93.0 gus n= pbogus n= gus* n= adagus n= 174 329 279 77.6 334 0 4 8 12 16 20 24 28 32 36 40 44 48 52 60 68 76 84 92 100 108 116 124 132 140 148 156 164 172 180 188 196 204 212 220 228 236 244 252 weeks m e d ia n ( iq r ) a b s o lu te p a s i pbo → guspbogus gus n = 329 329 pbo → gus n = 174 165 gus* n = 468 448 432 411 391 ada → gus n = 334 334 279 275 269 256 246 ada ada → gusgus* 0 5 10 15 20 25 0 0 0 0 0 0 0 0 1.8 2.00 0.1 0.1 error bars represent q1 and q3. *includes patients randomized to gus at baseline and those randomized to pbo at baseline who crossed over to gus at week 16. ada=adalimumab; gus=guselkumab; iqr=interquartile range; pasi=psoriasis area and severity index; pbo=placebo figure 2. median percent improvement from baseline in pasi (iqr) through week 252 0 4 8 12 16 20 24 28 32 36 40 44 48 52 60 68 76 84 92 100 108 116 124 132 140 148 156 164 172 180 188 196 204 212 220 228 236 244 252 0 20 40 60 80 100 weeks m e d ia n ( iq r ) p e rc e n t im p ro ve m e n t f ro m b a s e lin e pbo → guspbogus gus n = 329 329 pbo → gus n = 174 165 gus* n = 468 448 432 411 391 ada → gus n = 334 334 279 275 269 256 246 ada ada → gusgus* 100 100 100 100 100 100 100 90.1 99.4100 90.2 99.7 100 skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 705 brief article petaloid seborrheic dermatitis: a variant described primarily in skin of color rachel e. christensen, bs1, colleen drapcho powers, md2, chelsea s. mockbee, md2, robert t. brodell, md2 1 rutgers robert wood johnson medical school, new brunswick, nj 2 university of mississippi medical center, jackson, ms seborrheic dermatitis (sd) is a chronic condition characterized by erythematous patches and plaques with scale affecting body regions of high sebum production.1 sd has a distinct appearance described primarily in patients with skin of color (soc) termed “petaloid seborrheic dermatitis.” pink, hypopigmented polycyclic/arcuate coalescing rings with minimal scale slowly expand symmetrically over weeks from the classic sd distribution in the naso-labial folds, eyebrows, and hairline.1,2 two cases of petaloid sd are presented and the pathophysiologic basis for these findings is explored. a 29-year-old female presented with a 10month history of pruritus, hypopigmentation, and flaking of the scalp and face. ketoconazole 2% shampoo and ketoconazole 2% cream to affected areas resulted in little improvement. inspection revealed symmetrical, erythematous, hypopigmented, petaloid patches with scale and raised advancing borders present symmetrically across the nasolabial folds, cheeks, temples, conchal bowls, and eyebrows (figure 1a-1c). xerotic plaques with scale were also present across the midline upper back and central chest. recognizing the symmetry and classic distribution of petaloid seborrheic dermatitis, a koh preparation was not performed. treatment was initiated with ketoconazole 2% shampoo daily, ciclopirox 0.77% cream twice daily and hydrocortisone 2.5% ointment daily for facial plaques, and fluocinonide 0.05% solution daily and as needed for scalp itching. the condition cleared completely abstract petaloid seborrheic dermatitis is a distinct variant of seborrheic dermatitis most commonly affecting patients with skin of color. it is characterized by arcuate coalescing lesions with fine scale and a raised border that symmetrically expands over the course of weeks in a seborrheic distribution. two patients with extensive petaloid seborrheic dermatitis of the face are presented who quickly responded to a typical regimen for seborrheic dermatitis. recognition of petaloid seborrheic dermatitis will prevent misdiagnosis and improper treatment of this common condition. introduction case reports skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 706 figure 1. (a-c) symmetrical, erythematous, hypopigmented, petaloid patches with scale and raised advancing borders present symmetrically across the nasolabial folds, cheeks, temples, conchal bowls, and eyebrows. (d-f) clearance of plaques after ketoconazole 2% shampoo daily, ciclopirox 0.77% cream twice daily and hydrocortisone 2.5% ointment daily. figure 2. (a-c) diffuse scale throughout the scalp and erythematous, greasy, petaloid patches with scale, some with a raised advancing border, symmetrically involving the nasolabial folds and eyebrows. (d-f) complete clearance in one month with oral fluconazole 200 mg weekly, hydrocortisone 2.5% cream twice daily, ketoconazole 2% shampoo daily, and betamethasone dipropionate 0.05% ointment twice daily to the scalp and as needed for itching. skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 707 (figure 1d-1f). the topical steroids were tapered, and clearance was maintained with topical antifungals alone. an 18-year-old male presented with a hypopigmented, erythematous and flaky rash affecting the eyebrows, nose, and appearing diffusely in the scalp for five years. despite treatment with clotrimazole 1% cream, ketoconazole 2% shampoo, and betamethasone dipropionate 0.05% ointment, the rash intermittently flared. physical examination revealed diffuse scale throughout the scalp and erythematous, greasy, petaloid patches with scale, some with a raised advancing border, symmetrically involving the nasolabial folds and eyebrows (figure 2a-2c). a koh preparation was not performed because of the classic presentation of petaloid seborrheic dermatitis. treatment was initiated with oral fluconazole 200 mg weekly, hydrocortisone 2.5% cream twice daily, ketoconazole 2% shampoo daily, and betamethasone dipropionate 0.05% ointment twice daily to the scalp and as needed for itching. the condition cleared completely within one month (figure 2d-2f) and was well-controlled with ketoconazole 2% shampoo twice weekly applied to the face and scalp. petaloid sd is a distinct presentation of sd almost always affecting patients with soc.1,2 given the presentation of annular lesions and a raised edge, petaloid sd may be mistaken for tinea faceii, which can be excluded with a potassium hydroxide preparation, if needed. the symmetrical, central facial distribution and diffuse, fine scale argued against this diagnosis in our patients. syphilis may present similarly to petaloid sd with arcuate or annular plaques or patches on the face.3 that our patients had no lesions except in the seborrheic distribution, specifically no palm and sole involvement, argues against this diagnosis. psoriasis/sebopsoriasis could be considered, but our patients did not have the classic white micaceous scale on extensor surfaces or nail changes consistent with psoriasis. atopic dermatitis commonly occurs on the face in infants but would be unlikely to produce the chronic annular symmetrical patches seen in our patients. several scarring conditions could produce annular, dermal lesions including cutaneous sarcoidosis and discoid lupus erythematosus, but no scarring process was evident. finally, cutaneous t-cell lymphoma (ctcl) could be considered, but lesions would not be restricted to the seborrheic distribution and the poikiloderma typical of ctcl was not present. occasionally, a punch biopsy could exclude these dermal infiltrative or neoplastic conditions. the etiology of sd is unclear and undoubtedly multifactorial. development of symptoms is strongly linked to the presence of malassezia species.1 overactivity of sebaceous glands may also play a role, particularly given that excess sebum promotes malassezia growth.1 finally, an immunological response to the presence of malassezia on the skin contributes to disease pathogenesis. the underlying pathophysiology associated with petaloid sd in soc may differ from classic sd in some ways. one potential mechanism may be related to an increased inflammatory response to malassezia organisms in darker-skinned patients. soc, for unknown reasons, is associated with an increased inflammatory response in several dermatological conditions, such as acne vulgaris.4 of particular interest is the presence of polymorphonuclear leukocyte cell infiltrates within comedones, lesions discussion skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 708 figure 3. petaloid appearance of tinea versicolor. generally non-inflammatory in lighter-skinned patients.4 inflammatory pityriasis rosea is also more common in soc. it presents with a greater number of papular and plaque-like lesions of the scalp and face with post-inflammatory hyperpigmentation, more frequent involvement of oral mucosa, and more pruritus, when compared to light-skinned phenotypes.5,6 while the herald patch is often annular, multiple annular lesions occur in as many as 20% of patients.7,8 it is unclear from the literature if these annular lesions occur more commonly in soc. tinea versicolor (tv), a condition which like sd is associated with malassezia, may also produce greater inflammation in soc.6 when confluent, an exaggerated rim can have a petaloid appearance (figure 3). inverse tv is a variant commonly seen in soc which occurs on flexural areas, extremities, and the face. the latter location is notably spared in the classic presentation.9,6 in summary, pityriasis rosea, tv and sd can present with annular rings and a petaloid appearance that are not as commonly described in light-skinned patients.1,8 an increased inflammatory response in patients with soc may be driven by various mechanisms. genetic influences on sebum production may optimize skin for growth of resident flora.9 culturally promoted application of palm oil or cocoa butter may play a role as these substances are lipid-rich and may facilitate growth of malassezia in tv by altering the carbon dioxide concentration, epidermal flora, and ph of the skin.9,10 future research should explore histopathological features of inflammation at the advancing rim in patients with petaloid sd. it is also important to know more about the clinical response to anti-inflammatory topicals and more targeted anti-fungal agents designed to eliminate malassezia yeast. finally, an assessment of moisturizing products that may be preferentially utilized by patients with soc is needed to determine if their avoidance minimizes petaloid sd development. conflict of interest disclosures: robert t. brodell is a principal investigator for clinical trials (novartis and pfizer) the corevitas psoriasis biologic registry, and owns stock in veradermic, inc. he serves on editorial boards of american medical student research (faculty advisor); practice update dermatology (editor-in-chief); journal of the american journal academy of dermatology (associate editor); practical dermatology; journal of conclusion skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 709 the mississippi state medical society; skin: the journal of cutaneous medicine and archives of dermatological research. rachel christensen has no conflicts of interest. none of these disclosures are judged by the authors to be relevant to the subject matter of this article. funding: none corresponding author: rachel e. christensen, bs 125 paterson st. new brunswick, nj, 08901 phone: (732) 235-6200 email: rec154@rwjms.rutgers.edu references: 1. bolognia j, schaffer jv, cerroni l, eds. dermatology. 4th ed. elsevier; 2018. 2. elgash m, dlova n, ogunleye t, taylor sc. seborrheic dermatitis in skin of color: clinical considerations. j drugs dermatol. 2019;18(1):2427. 3. de carvalho fagundes fn, simoes jp, pereira magnago ag, de sousa brito xavier mh. annular and arcuate syphilis: an uncommon presentation of disseminated secondary syphilis. dermatol online j. 2018;24(4):13030/qt2nb2k1xd. 4. halder rm, holmes yc, bridgeman-shah s, kilgman am. a clinicohistopathological study of acne vulgaris in black females. j invest dermatol. 1996;106(4):888. 5. amer a, fischer h, li x. the natural history of pityriasis rosea in black american children: how correct is the "classic" description? arch pediatr adolesc med. 2007;161(5):503-506. 6. li, jc, kundu rv. tinea versicolor: in: love, p, kundu, r, eds. clinical cases in skin of color: adnexal, inflammation, infections, and pigmentary disorders. springer, cham; 2016. https://doi.org/10.1007/978-3-319-22392-6_11 7. aslan kayıran m, wang jv, karadag as. papulosquamous annular diseases. clin dermatol. 2022:s0738-081x(21)00265-0. doi: 10.1016/j.clindermatol.2021.12.007. 8. urbina f, das a, sudy e. clinical variants of pityriasis rosea. world j clin cases. 2017;5(6):203-211. doi:10.12998/wjcc.v5.i6.203 9. pontasch mj, kyanko me, brodell rt. tinea versicolor of the face in black children in a temperate region. cutis. 1989;43(1):81-84. 10. aly r, shirley c, cunico b, maibach hi. effect of prolonged occlusion on the microbial flora, ph, carbon dioxide and transepidermal water loss on human skin. j invest dermatol. 1978;71(6):378381. doi:10.1111/1523-1747.ep12556778 skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 585 brief article new onset generalized pustular psoriasis rapidly improved with il-36 blockade meredith burns, bs1, timothy orlowski, md2, hoang ho-pham, md2, carly elston, md2*, boni elewski, md2* *drs. elston and elewski contributed equally to this article 1heersink school of medicine, university of alabama at birmingham, birmingham, al 2department of dermatology, university of alabama at birmingham, birmingham, al generalized pustular psoriasis is an uncommon variant of psoriasis characterized by diffuse eruption of sterile pustules with potential for sepsis and organ failure. a paucity of reliably efficacious therapeutics has made this condition difficult to treat. interleukin-36 (il-36) receptor antagonists are emerging as a promising therapy for pustular psoriasis providing rapid and efficacious response. we present a case of generalized pustular psoriasis with complete response to spesolimab, an il-36 receptor antagonist monoclonal antibody that recently became the first fda-approved therapy for this condition. physicians should be familiar with this now treatable disorder. a 60-year-old female with past medical history of plaque psoriasis and psoriatic arthritis treated with guselkumab 100mg every 8 weeks presented to the emergency department with an acute generalized pustular dermatosis that developed after she received intramuscular triamcinolone and oral methylprednisolone to treat a presumable morbilliform drug eruption that developed after she was given oral clindamycin for paronychia. both her cutaneous and articular disease had been well-controlled on guselkumab since february 2021 with minimal localized cutaneous disease after failing therapy with adalimumab, etanercept, ustekinumab, abstract generalized pustular psoriasis is a relatively rare variant of psoriasis characterized by diffuse eruption of sterile pustules on an erythematous background. untreated flares can result in lifethreatening complications including sepsis and organ failure. generalized pustular psoriasis has historically proven challenging to treat with an unpredictable clinical course and paucity of reliably efficacious treatment options. until recently, there have been no fda-approved therapies for generalized pustular psoriasis in the united states. in september 2022, the il36 receptor antagonist spesolimab became the first fda-approved treatment for generalized pustular psoriasis in adults. we present a case of generalized pustular psoriasis with complete and rapid response to spesolimab. introduction case report skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 586 secukinumab, and ixekizumab. the patient had rapid generalization of her skin lesions with severe skin tenderness, fever of 103.9°f, chills, tachycardia, and leukocytosis. she was admitted to the intensive care unit. physical examination was notable for diffuse coalescing and isolated pustules within a background of erythema involving the face, neck, trunk, groin, upper extremities, and lower extremities. there was significant edema of the face, trunk, and extremities. two 4mm punch biopsies were performed from the left abdomen and left thigh. histologic sections demonstrated subcorneal and intraepidermal spongiform pustules consistent with pustular psoriasis. the patient was treated with a single intravenous infusion of spesolimab 900mg in addition to triamcinolone 0.1% ointment and hydrocortisone 1% cream. she had rapid and remarkable improvement within 18 hours of receiving spesolimab with almost complete resolution of superficial pustules and background erythema on the face, neck, trunk, and extremities. physical examination 40 hours following spesolimab treatment showed continued improvement with complete resolution of all remaining pustules. the infusion was well-tolerated, and the patient reported no adverse effects. she was discharged home two days post-infusion with a plan for 1 month follow-up in outpatient dermatology clinic, continuation of topical treatment, and continuation of guselkumab. generalized pustular psoriasis is a relatively rare and potentially fatal autoinflammatory dermatologic condition with marked impacts on patient quality of life. acute generalized pustular psoriasis commonly presents with accompanying systemic symptoms including fever, chills, malaise, and severe pain due to underlying systemic inflammation. untreated flares can result in life threatening complications including sepsis, renal failure, hepatic failure, and cardiorespiratory failure.1 corticosteroid use and withdrawal is a known trigger for generalized pustular psoriasis flares, and other potential triggers include smoking, pregnancy, stress, infections, lithium, tnf-alpha inhibitors, and nonsteroidal anti-inflammatory drugs.2,3,4 discussion skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 587 while the immunopathogenesis involved in the development of generalized pustular psoriasis is complex, studies have identified the il-36 pathway as a key element in the pathogenesis of this disorder.2 overexpression of il-36, or a loss-of-function mutation in the il-36 receptor antagonist il36ra, leads to increased levels of proinflammatory mediators and activation of il-36 receptors on skin cells.5,6 il-36, which belongs to the il-1 superfamily of cytokines, is vital to the homeostasis of the innate immune system. these family members include several cytokines, receptors, and accessory proteins that, when disturbed, can result in inflammatory dermatoses such as psoriasis.7 activation of il-1 cytokines with their receptors results in downstream action of nuclear factor kappa b, mitogen-activated protein kinases, and ultimately proinflammatory gene expression.7 in pustular psoriasis, unbalanced production of il-1 and il-36 contribute to autoinflammation, innate immune system activation, and neutrophilic infiltration of the epidermis, which leads to the clinical presentation of sterile pustules within a background of erythema.8 generalized pustular psoriasis has historically proven challenging to treat with an unpredictable clinical course characterized by persistent disease or intermittent relapsing flares. with previously available treatment options, a quarter of patients experience persistent pustular lesions despite systemic therapy.1 because of the severity of this disease and risk of sepsis and end-organ dysfunction, flares are generally managed in the inpatient setting with a 10 day average length of admission.1,2 until recently, there have been no approved therapies for generalized pustular psoriasis in the united states with a paucity of evidence-based treatment options. medical management of the disease has included the use of cyclosporine, systemic retinoids, methotrexate, and biologic agents.9 however, these treatments are often far less effective for pustular psoriasis compared to standard plaque psoriasis and can be associated with a multitude of adverse effects including hypertension, renal toxicity, and teratogenicity.10 in september 2022, the il-36 receptor antagonist spesolimab became the first fdaapproved treatment for generalized pustular psoriasis in adults. spesolimab is a humanized monoclonal antibody that blocks the il-36 receptor, thus inhibiting the ability of il-36 to bind and initiate proinflammatory cascades.10 while the exact impact of reduced il-36 receptor activity in generalized pustular psoriasis is undetermined, rapid and sustained improvement in clinical symptoms and inflammatory markers including creactive protein was demonstrated in effisayil phase 1 and 2 trials examining the efficacy of spesolimab.11,12 dosing of spesolimab in the treatment of generalized pustular psoriasis for adults is one 900mg intravenous infusion, then an additional 900mg infusion may be given one week later if the flare persists.12 imsidolimab is another il-36 receptor antagonist that is currently in phase 3 trials and has shown promising results for the treatment of pustular psoriasis.8 generalized pustular psoriasis should be considered in the differential diagnosis of any generalized pustular eruption. because of associated fever and systemic symptoms and the pustular nature of the disease, generalized pustular psoriasis is often misdiagnosed as an infectious disorder. primary care physicians, hospitalists, and emergency medicine physicians, who are conclusion skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 588 often seeing these patients at time of initial presentation, should be familiar with this now treatable disorder. this case highlights the potential of il-36 inhibitors to improve morbidity and mortality and shorten the duration of hospital admissions for patients with generalized pustular psoriasis. by targeting proinflammatory cytokines involved in the development of generalized pustular psoriasis, this emerging therapeutic provides rapid and effective response with less toxicity than existing therapies. conflict of interest disclosures: be disclosures include: clinical research support-research funding to university: abbvie, anaptys-bio, boehringer ingelheim, bristol myers squibb (bms), celgene, incyte, leo, lilly, merck, menlo, novartis, pfizer, regeneron, ucb, sun, valeant (ortho dermatology), vanda; consultant-received honorarium: amgen, arcutis, boehringer ingelheim, bms, celgene, leo, lilly, novartis, ucb, valeant (ortho dermatology). all other authors declare no conflicts of interest. funding: none corresponding author: boni elewski, md department of dermatology university of alabama at birmingham email: belewski@uabmc.edu references: 1. choon se, lai nm, mohammad na, nanu nm, tey ke, chew sf. clinical profile, morbidity, and outcome of adult-onset generalized pustular psoriasis: analysis of 102 cases seen in a tertiary hospital in johor, malaysia. int j dermatol. 2014;53(6):676-684. 2. menter a, van voorhees as, hsu s. pustular psoriasis: a narrative review of recent developments in pathophysiology and therapeutic options. dermatol ther (heidelb). 2021;11(6):1917-1929. 3. benjegerdes ke, hyde k, kivelevitch d, mansouri b. pustular psoriasis: pathophysiology and current treatment perspectives. psoriasis (auckl). 2016;6:131-144. published 2016 sep 12. 4. lowe nj, ridgway hb. generalized pustular psoriasis precipitated by lithium carbonate. arch dermatol. 1978;114(12):1788-1789. 5. gooderham mj, van voorhees as, lebwohl mg. an update on generalized pustular psoriasis. expert rev clin immunol. 2019;15(9):907-919. 6. marrakchi s, guigue p, renshaw br, et al. interleukin-36-receptor antagonist deficiency and generalized pustular psoriasis. n engl j med. 2011;365(7):620-628. 7. matarazzo l, hernandez santana ye, walsh pt, fallon pg. the il-1 cytokine family as custodians of barrier immunity. cytokine. 2022;154:155890. 8. iznardo h, puig l. il-1 family cytokines in inflammatory dermatoses: pathogenetic role and potential therapeutic implications. int j mol sci. 2022;23(16):9479. published 2022 aug 22. 9. robinson a, van voorhees as, hsu s, et al. treatment of pustular psoriasis: from the medical board of the national psoriasis foundation. j am acad dermatol. 2012;67(2):279-288. 10. shao s, wang g. commentary on a clinical trial of spesolimab, a humanized anti-interleukin-36 receptor monoclonal antibody, in generalized pustular psoriasis [published online ahead of print, 2022 oct 8]. dermatol ther (heidelb). 2022;10.1007/s13555-022-00830-x. 11. bachelez h, choon se, marrakchi s, et al. inhibition of the interleukin-36 pathway for the treatment of generalized pustular psoriasis. n engl j med. 2019;380(10):981-983. 12. bachelez h, choon se, marrakchi s, et al. trial of spesolimab for generalized pustular psoriasis. n engl j med. 2021;385(26):24312440. skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 84 skinmages ulcerations and lymphadenopathy in a 42 year old male nicholas brownstone, md1, mckenzie a. dirr, ba, bs2, darrell rigel, md, ms3 1 national society for cutaneous medicine, new york, ny 2 medical university of south carolina, charleston, sc 3 department of dermatology, mount sinai icahn school of medicine, new york, ny tuberculosis (tb) disease has remained a major global and public health challenge1. tb infection usually occurs in the lungs, but it can involve other body sites as well. this is known as extra-pulmonary tb, which accounts for about a tenth of newly diagnosed tb cases worldwide. about a third of newly diagnosed tb cases occur in the head and neck region (which includes the oropharynx, nasal cavities, ears, neck spaces and lymph nodes). the most common form of head and neck tb is cervical lymphadenopathy, also know as scrofula. the image presented here is of a 42 year old male who immigrated from laos. he presented to the dermatology clinic with a 2skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 85 month history of nodules in neck. after history and physical examination, a skin biopsy was performed which was positive for acid-fast bacilli, confirming the diagnosis of scrofula. while still a rare disease, it is important to be aware of this presentation, as extra-pulmonary tb has increased proportionally with rising total tb cases in industrialized countries from 7.6% in 1962 to 21% in 20063. the diagnosis of scrofula may include several investigative techniques, with clinical suspicion serving to direct the pursuit of diagnostic testing. imaging may aid clinical suspicion, as scrofula can present with four described characteristics on ct, as well as helpful doppler ultrasound findings consisting of distinct vascular changes4. additionally, it is useful to perform a chest xray and abdominal ultrasound to ensure the patient does not have pulmonary tb or tb afflicting a different anatomic region5. diagnostic steps include culturing a sample obtained from an affected lymph node, pcr, or histology with evidence of caseous necrosis within a granuloma5. the mainstay of scrofula treatment consists of a series of regimented combinations of antimycobacterial pharmacotherapy, initially selected among 4 guideline-directed options, chosen based on patient age, type, risk factors, and susceptibility6. this routinely includes 2 months of 4 drugs, typically consisting of rifampin, isoniazid, pyrazinamide, and ethambutol, with a subsequent 4or 7-month period of a dualdrug regimen6. however, as multi-drug resistant tb (tb that is nonresponsive to isoniazid and rifampin) has emerged, antibiotics such as fluoroquinolones are also considered, but these cases must be managed by specialists and follow strict guidelines set forth by the world health organization (who) and the international union against tuberculosis and lung disease (iu-atld)6. while the exact role of surgical treatment is yet to be established, surgical excisional intervention may be necessary in cases of large abscesses and scrofula resistant to treatment5,6. conflict of interest disclosures: none funding: none corresponding author: nicholas brownstone, md national society for cutaneous medicine new york, ny email: nickbrownstone34@gmail.com references: 1. phillips l. infectious disease: tb’s revenge. nature. 2013;493(7430):14-16. doi:10.1038/493014a 2. rieder hl, snider de, cauthen gm. extrapulmonary tuberculosis in the united states. am rev respir dis. 1990;141(2):347351. doi:10.1164/ajrccm/141.2.347 3. peto hm, pratt rh, harrington ta, lobue pa, armstrong lr. epidemiology of extrapulmonary tuberculosis in the united states, 1993-2006. clin infect dis off publ infect dis soc am. 2009;49(9):1350-1357. doi:10.1086/605559 4. rodriguez-takeuchi, sara yukie, martin eduardo renjifo, and francisco josé medina. “extrapulmonary tuberculosis: pathophysiology and imaging findings.” radiographics 39.7 (2019): 2023– 2037. web. 5. benjelloun, amine et al. “lymph nodes tuberculosis: a retrospective study on clinical and therapeutic features.” the pan african medical journal vol. 20 65. 23 jan. 2015, doi:10.11604/pamj.2015.20.65.5782 6. blumberg, h. m., burman, w. j., chaisson, r. e., daley, c. l., etkind, s. c., friedman, l. n., fujiwara, p., grzemska, m., hopewell, p. c., iseman, m. d., jasmer, r. m., koppaka, v., menzies, r. i., o'brien, r. j., reves, r. r., reichman, l. b., simone, p. m., starke, j. r., vernon, a. a., & american thoracic society, centers for disease control and prevention and the infectious diseases society (2003). american thoracic society/centers for disease control and prevention/infectious diseases society of america: treatment of tuberculosis. american journal of respiratory skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 86 and critical care medicine, 167(4), 603–662. https://doi.org/10.1164/rccm.167.4.603 https://doi.org/10.1164/rccm.167.4.603 skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 286 in-depth review contrasting between atopic dermatitis and psoriasis in the quality of life impact and the prevalence of psychiatric disorders: a review mimi chung, ba1, marwa hakimi, md1, samuel yeroushalmi, bs1, erin bartholomew, ba1, john koo, md1 1department of dermatology, university of california, san francisco, san francisco, ca atopic dermatitis (ad) and psoriasis (pso), as two of the most common inflammatory skin conditions, share many similarities including their chronic and relapsing nature. however, the differences between their impacts on quality of life measures is less researched, despite suggestions of differences between these two conditions. this article reviews what is known about the differences in the negative impact to people’s lives between ad and pso and tries to ascertain why some of these differences exist when they are both chronic inflammatory skin disorders. in the past 20 years, there have been tremendous advances made in the therapeutic options for pso, demonstrating significant improvements in both physical measures of disease activity and patient reported outcomes. as novel ad treatment options similarly begin to expand, the clinician should have an understanding of how these new modalities may also affect patients’ quality of life. though both conditions have serious impacts on quality of life, we aimed to determine if there were notable differences in psychological burdens and outcomes between patients with pso and those with ad. a literature search was conducted on medline for articles comparing the psychological outcomes of atopic dermatitis and psoriasis. keywords included “psychological comorbidities psoriasis atopic dermatitis,” “psychiatry psoriasis atopic dermatitis”, and “psoriasis atopic dermatitis abstract as chronic inflammatory skin conditions, psoriasis and atopic dermatitis have both been associated with significant psychosocial comorbidities. however, the similarities and differences between the two in the manifestation of psychologic/psychiatric sequalae have not been reviewed. we reviewed the current literature comparing these two skin conditions and determined that there are potentially notable differences in psychiatric impact between psoriasis and atopic dermatitis patients. for example, patients with atopic dermatitis appears to have more issues with attention deficit hyperactive disorder (adhd) and conduct disorder while psoriasis is associated more with suicidal acts. we propose that these may stem from the different ages of onset, which subsequently influences how the psychological impact manifests within the individual. introduction methods skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 287 mental health.” only english articles were considered. cross-sectional, retrospective, and prospective clinical trials and metaanalyses published from january 2000 to january 2022 were considered for the review. for this review, 115 studies were initially screened. after title and abstract screening, 21 full texts were assessed for eligibility. five articles were included in this review. the flowchart of studies is included in figure 1. there are very few studies which compare ad and pso directly in the medical literature. a summary of the included studies can be viewed on table 1. one such study comparing the prevalence of psychiatric disorders “head-to-head” was a study from korea. in this cross-sectional study, ahn et al compared 42,641 patients with ad and 139,486 patients with other skin conditions, including 5,323 pso patients of all ages. significant differences in the odds of developing different psychological outcomes were reported. the odds ratio (or) for ad patients to develop attentional deficit disorder (adhd) was significantly greater than nonad patient controls (or 1.25, 95% confidence interval [ci] 1.06 1.48, p < 0.01), as was the or for conduct disorder (2.74, 95% ci 1.30 5.78, p < 0.01). pso patients did not have significantly increased odds of either adhd (or 0.97, 95% ci 0.64 1.49, p = 0.9023) or conduct disorder (or 3.30, 95%ci 0.91 11.99, p = 0.0696). in contrast, pso patients were found to have significantly greater odds of anxiety and depression (or of 1.16 [95% ci: 1.03-1.30] and 1.38 [95% ci: 1.23-1.56], respectively) as well as sleep disorders (or 1.29 [95% ci: 1.14-1.47]). one limitation of this finding was that, though the study had balanced age distribution when comparing patients with ad and patients with other skin conditions, the demographics were not shown for the psoriasis group specifically.1 moreover, the ad population in this study clearly included a pediatric age group (younger than adolescents). however, it is not stated whether the pso comparator group in this study also included the younger pediatric population or not. therefore, the demographics of the ad group and the psoriasis groups in this korean study might have been significantly different in terms of age groups included. other studies that were not “head-to-head” comparisons resulted in outcomes that were different than these findings, though differences between the two conditions remain. a meta-analysis on depression outcomes in pso and ad patients found that both ad and pso patients had increased risk of suicidal ideation compared to controls (including studies that used general population or other medical conditions as controls). in 10 studies on suicidal ideation in pso, suicidal results skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 288 figure 1. summary diagram of studies screened skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 289 table 1. summary of the studies included in review source design study population outcome summary ahn et al 2019 cross-sectional cohort study n = 42,641 (ad) n = 5,323 (pso) patients with ad or patients with nonatopic eczema, urticaria, or pso ad patients had increased odds of adhd (1.25, 95%ci 1.06-1.48, p< 0.0091), while pso patients did not (or 0.97, 95%ci 0.94-1.64, p = 0.9023). ad patients also had increased odds of conduct disorder (2.74, 95%ci 1.30-5.78, p = 0.0084) compared to pso patients (3.30, 95%ci 0.91 11.99, p = 0.0696). the or for anxiety in pso patients was significant (1.03, 95%ci 1.03-1.30, p = 0.019), unlike ad patients (0.96, 95%ci 0.89-1.03, p =0.2056). similar results were seen for depression, with pso patients having an or of 1.38 (1.23-1.56) compared to ad patients (or 0.96, 95%ci 0.89-1.04, p = 0.3401). pso had higher or of sleep disorders (1.29, 95%ci 1.14-1.47, p < 0.0001), while ad patients did not (or 0.93, 0.86-1.02, p = 0.1134). ors for autism spectrum disorder, suicidal ideation, and schizophrenia were not significant for pso or ad patients. skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 290 pompili et al 2021 meta-analysis of 35 studies, which examined pso and ad. 27 studies on suicidal ideation and 19 studies on suicidal acts were included. some studies evaluated suicidal ideation and suicidal acts. patients with ad or pso compared with healthy controls or other dermatological/general medical disorders suicidal ideation for pso had a risk-ratio of 1.60 compared to controls. suicidal ideation for ad had a risk-ratio of 1.84 compared to controls. suicidal ideation was significantly greater in pso compared to controls (or 1.97, 95%ci 1.26-3.08, p = 0.003) and ad compared to controls (or 2.62, 95%ci 1.32-5.19, p = 0.006), but not pso compared to ad (1.47, 95%ci 0.91 2.35, p = 0.52). suicidal acts for pso had a risk-ratio of 2.51 compared to controls, while the risk-ratio for ad was 2.81. suicidal acts were significantly greater in pso compared to controls (or 1.42, 95%ci 1.05-1.92, p = 0.02) but for not ad patients compared to controls (or 1.53, 0.96-2.45, p = 0.08). though suicidal acts were higher in pso patients than ad patients, no or difference was found between pso and ad patients due to the confidence interval crossing 1 (or 1.47, 95%ci 0.91-2.35, p = 0.11). magin et al 2008 cross sectional study n = 108 (dermatological disease; n = 27 [pso], n = 17 [ad]) n = 96 (control) patients with pso, ad, or acne compared to healthy controls patients with dermatologic disorders had significantly greater ratings of fenigstein public self-consciousness (13.7, 95%ci 12.9-14.5) than controls (12.2, 95%ci 11.3–13.1), p = 0.015. patients with dermatologic disorders were also found to have worse eysenck neuroticism scores (5.1, 95%ci 4.7-5.5) compared to controls (4.5, 95%ci 4.0–5.0), p = 0.044. no difference was found among various skin diseases. skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 291 leibovici et al 2010 cross sectional study n = 37 (pso) n = 31 (ad) n = 31 (controls) patients with ad or pso compared with healthy controls pasi for pso patients and scorad scores for ad patients showed moderate disease for all patients. pruritis was higher on average in ad patients (4.42 on itch vas) than pso patients (2.57), p = 0.013. however, there was no significant difference in measurements of the itch-scratch cycle between ad and pso patients (mean 21.5 and 19.6, respectively) as measured by the adjustment to chronic skin diseases questionnaire. pso patients had worse well-being scores (mean 51.1), worse psychological distress (61.4), and worse overall outcomes (157.7) on the mental health inventory compared to ad patients (wellbeing mean 53.3, distress 55.7, total 165.5), p < 0.05. social anxiety was significantly worse in pso patients (33.8) than ad patients (26.6), with greater impact on quality of life (13.1 and 10.3, respectively), p < 0.05. no differences were found in helplessness or anxious-depressive mood. schut et al 2022 cross sectional study n = 5487 (n = 1383 (pso), n = 345 (ad)) n = 2754 (controls) patients with dermatological disorders the odds ratio of having body dysmorphic disorder was increased for both ad (odds 8.97, 95%ci 6.08-13.25) and pso patients (odds 7.63, 95%ci 5.64-10.33) compared to controls. significant values for the odds ratio remained after controlling for sex, age, income, stress, comorbidities, and bmi. abbreviations: ad, atopic dermatitis; pso, psoriasis; adhd, attention deficit personality disorder; or, odds ratio; pasi, psoriasis area and severity index; scorad, scoring atopic dermatitis; ci, confidence interval; vas, visual analogue scale skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 292 ideation was found to have an odds ratio of 1.97 (95%ci, 1.26 3.08; p = 0.003) compared to controls, while ad patients had an odds ratio of 2.62 from 16 studies (95%ci, 1.32 5.19, p = 0.006). however, only pso was found to be significantly associated with suicidal acts, with an or of 1.42 (95%ci 1.05 1.92) compared to controls (p = 0.02). ad patients, in contrast, had nonsignificant odds of suicidal acts compared to controls (or 1.53, 95%ci 0.96 2.45, p = 0.08). when comparing the ad and pso studies together, the risk of suicidal ideation and acts were greater for pso, though not significant. this nuance in measures of suicidality remained despite controlling for the type of control used in the clinical trial, study size, or year of study. of note, 22 of the 27 studies regarding suicidal ideation and 11 of 19 studies on suicidal acts were conducted on adults only, with few including adolescents and children.2 in a comparative study on dermatologic disease burden conducted in australia, pso and ad patients were found to have higher levels of public self-consciousness and neuroticism than controls, though no differences were seen between the two disease states. interestingly, this cohort did not show an increase in depression, anxiety, or introversion between pso and ad patients compared to the healthy controls. this study demonstrates that, beyond psychiatric outcomes such as suicidality, these chronic skin conditions can influence even psychological characteristics like neuroticism and self-consciousness.3 a case-control series conducted in israel examined psychological outcomes of pso and ad patients using a variety of mental health questionnaires. on physical measurement of disease, both groups had approximately similar severity of disease – moderate for both disorders based on the scoring atopic dermatitis (scorad) or the psoriasis area and severity index (pasi) – though ad patients had worse pruritus. however, pso patients showed consistently worse scores on the psychological distress scales. compared to controls, pso patients had statistically worse depression, anxiety, and behavioral-emotional control (as measured by the mental health inventory); well-being; and mental health total scores (all p < 0.05). these results were not seen in ad patients, who did not show significant differences from controls. moreover, pso patients reported more social anxiety/avoidance with a greater impact on quality of life than ad patients (p < 0.05). interestingly, despite the worse pruritus in ad patients, itch-scratch cycle results were the same for both disease groups.4 a study conducted in europe on body dysmorphia in adults with various skin conditions included 1383 pso patients and 244 ad patients. compared to controls, body dysmorphia was found to have greater odds to occur in pso patients (or = 7.65) and ad patients (or = 8.08), even after adjusting for sex, age, income, stress, medical comorbidities, and bmi. when comparing between various dermatologic patients, the risk of body dysmorphia was significantly related to younger age, female gender, and higher self-rated stress and stigmatization. pso and ad were not directly compared in this study, but a clear increase in body dysmorphia symptoms occurred in both group.5 in this paper, going beyond the quality of life measures such as dermatology quality of life index (dlqi), the authors have reviewed available medical literature regarding the prevalence of psychiatric disorders discussion skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 293 contrasting between ad and pso. though studies examining direct comparisons of these two diseases are sparse, potential differences in their presentation have been suggested in psychiatric comorbidities as well as negative psychosocial impact. for example, it has been noted in “head-to-head” comparison studies that ad patients tend to have more problems with adhd and conduct disorder, while pso patients tend to have more problems with suicidal acts, anxiety, and, in some studies, sleep disorders. the authors interpreted that the average age of onset for these conditions my contribute to these notable differences. as seen in figure 2, ad prominently affects children, even though there are others who have adult onset of this disease. in contrast, pso primarily affects adults in their early adulthood and late adulthood. the typical ad patient may be initiated to the disorder differently than pso patients with new onset pso – as a child, ad patients are less likely to have their self-identity and self-esteem fully established when ad first occurs. in contrast, pso patients generally are in their late adolescence or middle adulthood, with consequently better-established self-identity, body image, and self-esteem. applying principles of developmental psychology, early ad patients are likely to be in the sensorimotor or preoperational cognitive stage, during which they must directly interact with the environment to understand their surroundings and have yet to develop abstract thought. pso patients, however, are likely to be in formal operative operation state, able to apply theoretical concepts and develop personal analysis of their situation. this suggests that many ad patients, especially the pediatric age group, may not be able to articulate such concepts as depression or suicidal ideation; it takes maturity, including emotional understanding as well as linguistic sophistication, to report that one is depressed, anxious, or suicidal. patients who are pre-operational, such as the pediatric age group, tend to express depression as conduct disorder due to an inability to verbally express their complex emotional state, while adults can more readily articulate their psychological state. lastly, adults may be physically more able to carry out suicidal acts compared to underage pediatric populations. figure 2. age of onset of psoriasis and atopic dermatitis. the above illustration is a general representation of the age of onset of psoriasis versus atopic dermatitis and does not represent exact datapoints. therefore, some of the differences may be strongly reflective of the age of onset of the typical patient population. this difference in the negative impact of ad compared to pso may not be limited to the negative impact on the patients themselves; it may also spill over into family dynamics. it has been noted that ad affects parents of patients significantly – parents have been found to be more anxious and stressed, and tend to be more overprotective with atopic dermatitis children.6,7 presumably, the parenting differences can similarly lead to relationship stressors among conclusion skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 294 siblings, though less literature has examined the negative effect of ad on the sibling relationship. lastly, the caretaker burden for pediatric ad patients can be notably greater in a manner different from pso patients, the vast majority of whom are in adolescence and adulthood. these differences noted in the negative psychological impact between ad and pso may be relevant to dermatology providers in order to optimize the care of these patients. conflict of interest disclosures: mimi chung, marwa hakimi, samuel yeroushalmi, and erin bartholomew have no conflicts of interest to report. john koo is an advisor and speaker for abbvie, amgen, janssen, eli-lilly, leo pharma, novartis, pfizer, sun pharma, orthodermatologic, regenron/sanofi, and epi. he is an advisor for arcutis, dermavant, and castle pharmaceuticals. funding: none corresponding author: mimi chung department of dermatology university of california, san francisco 515 spruce street san francisco, ca 94118 email: mimi.chung@ucsf.edu references: 1. ahn hj, shin mk, seo jk, et al. cross-sectional study of psychiatric comorbidities in patients with atopic dermatitis and nonatopic eczema, urticaria, and psoriasis. neuropsychiatr dis treat. 2019;15:1469-1478. doi:10.2147/ndt.s191509 2. pompili m, bonanni l, gualtieri f, trovini g, persechino s, baldessarini rj. suicidal risks with psoriasis and atopic dermatitis: systematic review and meta-analysis. j psychosom res. 2021;141:110347. doi:10.1016/j.jpsychores.2020.110347 3. magin p, pond c, smith w, watson a, goode s. a cross-sectional study of psychological morbidity in patients with acne, psoriasis and atopic dermatitis in specialist dermatology and general practices. j eur acad dermatol venereol. 2008;22(12):1435-1444. doi:10.1111/j.14683083.2008.02890.x 4. leibovici v, canetti l, yahalomi s, et al. well being, psychopathology and coping strategies in psoriasis compared with atopic dermatitis: a controlled study. j eur acad dermatol venereol jeadv. 2010;24(8):897-903. doi:10.1111/j.14683083.2009.03542.x 5. schut c, dalgard fj, bewley a, et al. body dysmorphia in common skin diseases: results of an observational, cross-sectional multi-centre study among dermatological out-patients in 17 european countries. br j dermatol. published online january 18, 2022. doi:10.1111/bjd.21021 6. ristic g, nikolic ar, radovanovic s, radevic s. atopic dermatitis: the impact of personality properties of affected children and parental styles of care. eur j dermatol ejd. 2020;30(3):251258. doi:10.1684/ejd.2020.3760 7. nguyen cm, koo j, cordoro km. psychodermatologic effects of atopic dermatitis and acne: a review on self-esteem and identity. pediatr dermatol. 2016;33(2):129-135. doi:10.1111/pde.12802 powerpoint presentation › diagnostic discordance in cutaneous melanocytic lesions is well documented, and it is particularly prevalent among difficult-to-diagnose cases, for which histopathology may be insufficient for a definitive diagnosis.1-4 › the 23-gene expression profile (gep) and 35-gep tests are clinically available, objective ancillary tools that facilitate diagnosis of melanocytic lesions with ambiguous histopathology. the tests use proprietary algorithms to produce results of: suggestive of benign neoplasm; intermediate (cannot rule out malignancy); or suggestive of malignant neoplasm.5-7 › the gep tests have demonstrated accuracy metrics of 90.4 – 94.9% sensitivity and 92.5 – 96.2% specificity for the 23-gep, and 94.7 – 99.1% sensitivity and 89.5 – 94.3% specificity for the 35-gep.5-7 › today, both the 23and 35-gep tests are offered from a single laboratory. under the current laboratory workflow, unless preferred otherwise by the ordering clinician, clinical samples are processed first through the 23-gep test, and if a technical failure or intermediate result is received, processed through the 35-gep (figure 1). however, both are run independently of one another and can be ordered as stand-alone tests.8 subtype performance of the ancillary diagnostic 23and 35-gene expression profile (gep) tests for difficult-todiagnose melanocytic lesions background acknowledgments & disclosures references › jap has served as a consultant for castle biosciences, inc. sie is a consultant and shareholder of castle biosciences, inc. kla, jjs, bhr, jhr, jkw, sjk, and msg are employees and shareholders of castle biosciences, inc. km has served as a consultant and investigator for studies supported by castle biosciences, inc. this study was supported by castle biosciences, inc. results jose a plaza, md1, sarah i estrada, md2, brooke h russell, phd3, jennifer j siegel, phd3, jason h rogers, msc3, jeffrey k wilkinson, phd3, sarah j kurley, phd3, matthew s goldberg, md3,4, and kiran motaparthi, md5 1 depts of dermatology & pathology, the ohio state univ wexner medical center, columbus, oh, usa 2 affiliated dermatology, scottsdale, az, usa 3 castle biosciences, inc., friendswood, tx, usa 4 icahn school of medicine at mount sinai, ny, usa 5 dept of dermatology, univ of florida college of medicine, gainesville, fl, usa for more information: josea.plaza@osumc.edu methods ›the 23and 35-gep diagnostic test workflow results in high accuracy across a large spectrum of subtypes of melanocytic neoplasms conclusions table 1. gep workflow overall performance accuracy metrics figure 1. current clinical gep workflow presented at the inaugeral winter clinical – miami™ 2023 meeting , february 17-20, 2023. miami, florida scan or click here for more info table 2. gep workflow test result by lesion subtype (as indicated by submitting dermatopathologist) the performance of the 23and 35-gep tests using the clinical workflow was tested on unequivocal cases from a variety of subtypes ›. › melanocytic lesions and associated de-identified clinical data from patients ≥ 18 years of age were included in this study. samples were acquired under an irb-approved protocol, including those previously submitted for clinical testing for the 31-gep melanoma prognostic test. samples were independently reviewed (blinded to the original diagnosis) by at least 3 total dermatopathologists for adjudication and included if they received at least 2 out of 3 diagnostic concordance with choices of benign, malignant, or uncertain malignant potential (ump) (table 1). subtype in this analysis was determined by the submitting dermatopathologist. all cases not receiving a benign or malignant result from the 23-gep were run on the 35-gep. final gep workflow result subtype* benign, n intermediate, n malignant, n melanomas (n=245) acral lentiginous 15 common 15 desmoplastic 20 lentigo maligna 1 30 melanoma in situ 16 nodular 4 77 not specified 1 4 spitzoid 3 17 superficial spreading 1 41 benign nevi (n=100) blue 28 1 1 compound 9 3 compound dysplastic 26a 1 3b deep penetrating 1 intradermal 1 1 junctional dysplastic 13c 1d 4e spitz 7 performance cohort, n=350 95% confidence interval sensitivity 96.0% 92.0% – 99.0% specificity 87.8% 80.8% – 93.8% positive predictive value 89.0% 83.8% – 94.1% negative predictive value 95.6% 91.1% – 98.9% intermediate result 1.5% *5 samples did not have adequate subtype information. dysplastic nevi had different degrees of atypia: a: 13 mild, 2 moderate; b: 2 mild, 1 moderate; c: 6 mild, 4 moderate; d: 1 moderate; e: 3 mild, 1 moderate. table 3. gep workflow performance accuracy metrics by lesion subtype subtype* n sensitivity specificity melanomas acral lentiginous 15 100% common 15 100% desmoplastic 20 100% lentigo maligna 31 96.8% melanoma in situ 16 100% nodular 81 95.1% spitzoid 20 85% superficial spreading 42 97.6% benign nevi blue 30 93.3% compound dysplastic 30 86.7% junctional dysplastic 18 72.2% *only subtypes with n ≥ 15 are shown. results 1. shoo, b. a. et al. j am acad dermatol 2010. 62 (5) 751–756. 2. gerami, p. et al. am j surg pathol 2010. 34 (6) 816–821. 3. haws, b. et al. j cutan pathol 2012. 39 (9) 844–849. 4. elmore, j. g. et al. bmj 2017. 357 (1) j2813. 5. clarke, l. e. et al. j cutan pathol 2015. 42 (4) 244–252. 6. clarke, l. e. et al. cancer 2017. 123 (4) 617–628. 7. estrada, s. et al. skin 2020. 4 (6) 506–522. 8. goldberg, m. et al. skin 2021.5 s79. *technical fail includes samples with insufficient quantity of rna and/or control or discriminant gene amplification failure based on the requirements for each test. clinically, the technical failure rate for the gep workflow is ~0.2%.8 https://castletestinfo.com/mypath-melanoma-diffdx-melanoma/scientific-references/ https://castletestinfo.com/mypath-melanoma-diffdx-melanoma/scientific-references/ dd_01_036 wc miami 2023 eposter dgep workflow subtypes wide v1 slide 1 skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 172 short communication percutaneous penetration: reliability of mathematical models anuk burli, bs1,2, rebecca m. law, md1,3, howard i. maibach, md1 1 department of dermatology, university of california, san francisco, san francisco, ca 2 university of rochester school of medicine and dentistry, rochester, ny 3 memorial university of newfoundland school of pharmacy in the 300,000 years of homo sapiens evolvement, only in the last century and a half have large numbers of humans been extensively exposed to chemicals via skin exposure. although we have a global understanding of factors that control percutaneous penetration, experimental human in vivo data for few compounds exist suggesting the need for qsar based algorithms to predict fluxbased on chemical structure. several such models exist such as the potts and guy model, the cleek and bunge model and in silico models, but how accurately do they predict the human in vivo available data?3. our recent publications focused on the highest quality in vivo data available for organic compounds and steroids1,2. we analyzed in vitro and in vivo percutaneous penetration data for various organic compounds and steroids and calculated in vitro flux based on the most prominent model used by the epa for percutaneous penetration: potts and guy model. we then calculated in vivo flux based on the maximal absorption rate and applied dose. for most chemicals, the flux was over or underestimated by a factor 10–100. possible factors for the discrepancy between in vivo and in vitro data include the principle of rubbing and skin washing, which can affect the stratum corneum, a main barrier for skin absorption. additionally, anatomical variation in penetration exists due to a difference in stratum corneum thickness in different regions of the body. finally, each subject’s age differed and age can affect stratum corneum content. we also discuss limitations of the potts and guy model. the model relies on the variables log koctanol, saturated aqueous solubility, kp, and molecular weight, most of which are based on predictive models. percutaneous penetration data regarding the use of sunscreens has also been recently studied. sunscreen percutaneous penetration depends on blood level or urinary excretion. a recent fda study, involved widespread sunscreen application throughout the body, matta et al., found fairly high blood levels, indicating that the percutaneous absorption of sunscreen was at a level of concern4. however, this research relied on calculating area under the curve. when measuring percutaneous penetrations by this method, it is unclear whether a compound is being excreted or stored systematically in the body. systematic toxicity based on percutaneous penetration depends on absorption, distribution, metabolism and excretion. by not knowing how all four factors are affected through widespread sunscreen application, skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 173 information regarding percutaneous penetration is incomplete. percutaneous penetration relies on the different factors mentioned above. however, there is not yet a model that incorporates all these factors in predicting human in vivo percutaneous penetration. there are major public health implications because we are not accurately predicting how much organic compounds in our environment are being percutaneously absorbed through skin. it is necessary for the experimental community to further investigate how best to predict percutaneous penetration, as well as for clinicians who prescribe topical medications to further understand the limitations of current established mathematical models. availability of data and material: the data that support the findings of this study are available from the corresponding author, anuk burli, upon reasonable request conflict of interest disclosures: none funding: none corresponding author: anuk burli 601 elmwood avenue rochester, new york, 14620 email: burlianuk@gmail.com references: 1. burli a, law rm, rodriguez j, maibach hi, (2020). organic compounds percutaneous penetration in vivo in man: relationship to mathematical predictive model. regul toxicol pharmacol.112:104614. doi: 10.1016/j.yrtph.2020.104614. 2. burli a, law rm, maibach hi. ability of mathematical models to predict human in vivo percutaneous penetration of steroids. regul toxicol pharmacol. 2021 nov;126:105041. doi: 10.1016/j.yrtph.2021.105041. epub 2021 sep 6 3. cheruvu hs, liu x, grice je, roberts ms., (2020). modeling percutaneous absorption for successful drug discovery and development. expert opin drug discov. 15(10):1181-1198. doi: 10.1080/17460441.2020.1781085. 4. matta mk, florian j, zusterzeel r, et al. effect of sunscreen application on plasma concentration of sunscreen active ingredients: a randomized clinical trial. jama. 2020;323(3):256–267. doi:10.1001/jama.2019.20747 mailto:burlianuk@gmail.com accuracy and confidence among new first-year dermatology residents in the diagnosis of common dermatologic conditions in different fitzpatrick skin types anuj pranav sanghvi, bs1, david wang, md2, matthew lipner, md, phd2, kelly tackett, md, mph2, heather holahan, md2, and julie mervak, md2 1school of medicine, university of north carolina at chapel hill, chapel hill, nc 2department of dermatology, university of north carolina at chapel hill, chapel hill, nc • minority groups associated with darker fitzpatrick skin types are disproportionately affected by disparities in dermatologic care1-2 • dermatologic conditions in darker skin types are underrepresented in many training resources3-4 • previous studies have queried medical students’ recognition of skin conditions in different skin types5, but no similar studies have been published evaluating the abilities or comfort level of dermatology residents • the purpose of this study was to identify differences in the accuracy and confidence of new dermatology residents in diagnosing common dermatologic conditions in different fitzpatrick skin types synopsis and objective methods • distributed an online survey to new first-year dermatology residents at us acgme-accredited dermatology programs • participants were shown 20 photographs of common dermatologic conditions in patients of varying fitzpatrick skin types • for each image, participants selected a diagnosis from a drop-down menu and rated their confidence in each diagnosis from 1 (“not confident at all”) to 5 (“very confident”) • participants also reported their confidence in diagnosing common dermatologic conditions in different fitzpatrick skin types in a preand post-survey questionnaire. • survey data were analyzed using descriptive statistics, unpaired ttests, one-way analysis of variance tests, pairwise correlation tests, and wilcoxon matched-pairs signed-rank tests • fifty first-year dermatology residents (10% response rate) completed the survey. methods • the small sample size may have skewed the results • response rate was limited by voluntary participation • survey was closed at the end of the first month of training to reduce confounding from inter-program differences • the number of common skin conditions in the survey was limited out of consideration for the time • survey did not fully represent the spectrum or prevalence of skin conditions seen in the practice of dermatology limitations • new dermatology residents diagnose common dermatologic conditions in darker skin with less accuracy and confidence than in lighter skin • there is a lack of statistical significance with participants’ demographics and background characteristics • differences identified in diagnostic accuracy and confidence may stem from a systemic deficiency in skin of color education rather than individual backgroundsnd confidence in lighter versus darker fitzpatrick skin types may stem from a systemic deficiency in skin of color education rather than individual backgrounds. conclusions 1.buster kj, stevens ei, elmets ca. dermatologic health disparities. dermatol clin. 2012;30(1):53-viii. doi:10.1016/j.det.2011.08.002 2.tripathi r, knusel kd, ezaldein hh, scott jf, bordeaux js. association of demographic and socioeconomic characteristics with differences in use of outpatient dermatology services in the united states. jama dermatol. 2018;154(11):1286-1291. doi:10.1001/jamadermatol.2018.3114 3.ebede t, papier a. disparities in dermatology educational resources. j am acad dermatol. 2006;55(4):687-690. doi:10.1016/j.jaad.2005.10.068 4.alvarado sm, feng h. representation of dark skin images of common dermatologic conditions in educational resources: a cross-sectional analysis. j am acad dermatol. 2021;84(5):1427-1431. doi:10.1016/j.jaad.2020.06.041 5.fenton a, elliott e, shahbandi a, et al. medical students' ability to diagnose common dermatologic conditions in skin of color. j am acad dermatol. 2020;83(3):957-958. doi:10.1016/j.jaad.2019.12.078 references results figure 1 (left). accuracy of incoming dermatology residents in diagnosing common dermatologic conditions figure 2 (right). confidence of incoming dermatology residents in diagnosing common dermatologic conditionsa * signifies significant difference (p<0.05) a confidence was scored on a scale of 1 (“not confident at all”) to 5 (“very confident”) powerpoint presentation -28.2 -23.3 -11.9 -30 -25 -20 -15 -10 -5 0 1 % c h a n g e f ro m b a se li n e i n s ca li n e ss -25.4 -18.7 -9.8 -30 -25 -20 -15 -10 -5 0 1 % c h a n g e f ro m b a se li n e i n m pa s i 34.7 26.2 13.7 0 5 10 15 20 25 30 35 40 % p g a i m p ro ve m e n t • patients scored the psoriasis treatment convenience of cal/bdp cream significantly higher than for cal/bdp ts. • finally, more patients in the cal/bdp cream group (44.8%) achieved a clinically relevant 4-point improvement in dermatology life quality index (dlqi) at week 1 than with cal/bdp ts (40.4%; p=0.0476) or vehicle (29.7%) (figure 3). • the patient populations included in this analysis are presented in table 1. • pga improved at least 1-grade after one week of treatment in 34.7% of patients with cal/bdp cream compared to 26.2% in the cal/bdp ts group (p=0.0122) and 13.7% in the vehicle group (p<0.0001) (figure 1a). • the mpasi score decreased more in the cal/bdp group (25.4% change from baseline) after one week of treatment compared to the cal/bdp ts group (18.7%; p=0.0013) and the vehicle group (9.8%; p<0.0001) (figure 1b). results george han1, steve r. feldman2, neal bhatia3, morten præstegaard4 1department of dermatology, zucker school of medicine at hofstra/northwell, new hyde park, new york; 2department of dermatology, wake forest school of medicine, winston-salem, north carolina; 3therapeutics clinical research, san diego, california; 4mc2 therapeutics, hørsholm, denmark calcipotriene (cal) and betamethasone dipropionate (bdp) cream (cal 0.005%/bdp 0.064% w/w) improves plaque psoriasis at week one in a phase 3 trial • improved adherence to therapy is one of the greatest unmet needs associated with topical psoriasis medication. early onset of action and convenience are key adherence drivers1. scaling and itching are burdensome psoriasis symptoms2, and rapidly effective treatment could improve adherence and quality of life. • calcipotriene (cal) and betamethasone dipropionate (bdp) cream is an effective and highly convenient psoriasis treatment made possible by pad™ technology. introduction • writing support was provided by anja snel-prentø, medlink. • the study was funded by mc2 therapeutics. acknowledgements conclusions • cal/bdp cream is an innovative topical treatment for plaque psoriasis based on pad™ technology. • in this head-to-head trial, cal/bdp cream demonstrated a faster onset of action than cal/bdp ts. rapid improvement of both clinical (pga and mpasi) and patient reported outcomes (itch, dlqi, and psoriasis treatment convenience) provides potential for cal/bdp cream to facilitate increased adherence to treatment and better treatment outcomes for patients with psoriasis. methods • we compared the onset of action, efficacy and safety of cal/bdp cream vs vehicle and active comparator cal/bdp topical suspension (ts) in 796 adults with mild to moderate plaque psoriasis (physician global assessment (pga) 2 or 3) enrolled in a phase 3, randomized, multicenter, investigator-blind, parallelgroup trial (nct03308799). • patients were instructed to apply the trial medication topically to affected areas of the body once daily for up to 8 weeks. • statistical analyses were based on an intent-to-treat (itt) population or modified itt (including all patients with at least one assessment of pga after starting treatmen). for pga, mpasi, itch and dlqi multiple imputation for missing data were applied. for ptcs last observation carried forward for missing data were applied. scaliness was based on observed cases. table 1. patient population figure 1. (a) pga improvement and (b) mpasi change from baseline, after one week of treatment pga, physician global assessment. mpasi, modified pasi. dlqi, dermatology life quality index. ptcs, psoriasis treatment convenience scale, nrs, numerical rating scale. bdp, betamethasone dipropionate; cal, calcipotriene; ts, topical suspension. mitt, modified intent-to-treat population including all patients with at least one pga assessment after starting treatment. figure 2. scaliness (a) and itch (b) after one week of treatment • improvement of mpasi at week 1 was supported by a reduction in scaliness of 28.2% in patients treated with cal/bdp cream compared to 23.3% (p=0.0722) in patients treated with cal/bdp ts and 11.9% in patients treated with vehicle (p<0.0001) (figure 2a). • further, a greater proportion of patients (44.0%) treated with cal/bdp cream achieved at least a 4-point improvement in peak pruritus numerical rating scale (nrs) score during the first week of treatment in comparison to cal/bdp ts (36.9%; p=0.0241) and vehicle (20.4%; p<0.0001) (figure 2b). 1feldman sr. cutis. 2013. 2korman et al., clin exp dermatol. 2016. references figure 3. dlqi improvement at week 1 cal/bdp cream cal/bdp ts cream vehicle itt population 342 337 115 modified itt population 338 334 112 p=0.0122 p<0.0001 p<0.0001 p=0.0013 p<0.0001 p=0.0722 p<0.0001 a) b) a) b) cal/bdp cream cal/bdp ts cream vehicle cal/bdp cream cal/bdp ts cream vehicle figure 4. improvement of plaque psoriasis after one week of treatment with cal/bdp cream in patients with psoriasis baseline week 1 week 1baseline pga improvement mpasi change from baseline scaliness itch pictures from mc2-01-c7 phase 3 trial; informed consent to publish pictures has been obtained from the patient. p=0.0241 44.0 36.9 20.4 0 5 10 15 20 25 30 35 40 45 50 % o f p a ti e n ts w it h a 4 -p o in t n r s im p ro ve m e n t 44.8 40.4 29.7 0 5 10 15 20 25 30 35 40 45 50 % o f p a ti e n ts w it h d lq i im p ro ve m e n t cal/bdp cream cal/bdp ts cream vehicle p=0.0476 baseline week 1 powerpoint presentation introduction results methods references conclusions clinical implications baseline; iga 4 week 12; iga 1 14-year-old white male chest back baseline; iga 3 week 12; iga 1 13-year-old hispanic female chest back marked truncal acne response to sarecycline monotherapy in different ethnicities angela yen moore1,2, stephen moore1,3, luke moore1, ayman grada4, stephen k tyring3 1arlington research center, arlington, tx, usa; 2baylor university medical center, dallas, tx, usa 3department of dermatology, the university of texas mcgovern medical school, houston, tx, usa; 4grada dermatology research llc, chesterbrook, pa, usa ▪ 60-70% of patients present with acne on the trunk.1 ▪ since severity of truncal acne does not correlate with severity of facial acne, the psychosocial burden and physical pain and bleeding of truncal acne cannot be underestimated. 2 ▪ oral antibiotics are the mainstay treatment for moderate-to-severe acne vulgaris. ▪ sarecycline, a narrow-spectrum tetracycline-class drug, is fda-approved for moderate-to-severe acne vulgaris in patients 9 years of age and older. ▪ sarecycline exhibits potent anti-inflammatory activity and activity against c. acnes but reduced activity against gram-negative bacteria commonly found in the gut; these characteristics may contribute to its low potential for antibiotic resistance and favorable safety and tolerability profile. 3 ▪ significant improvement in truncal acne, using iga assessments, was reported with sarecycline in phase 3 clinical trials. 4,5 ▪ we present 2 patients treated with sarecycline monotherapy for 3 months. ▪ at baseline, weeks 3, 6, 9 and 12, we assessed iga scores and lesion counts change of the trunk. baseline data demographics skin phototype truncal iga truncal lesion count* facial lesion count* 14 yo white male 2 4 47 8 13 yo hispanic female 4 3 29 28 * inflammatory lesions (papules and pustules) inflammatory lesion count reduction demographics baseline 3 wks 6 wks 9 wks 12 wks 14 yo white male 47 22 (53%) 8 (83%) 1 (98%) 2 (96%) 13 yo hispanic female 29 16 (45%) 4 (86%) 2 (93%) 3 (90%) ▪ no side effects of special interest for tetracycline-family antibiotics, including nausea, diarrhea, esophagitis, pseudotumor cerebri, blurry or double vision, dizziness, vertigo, or blue-gray pigmentation, were observed. ▪ this case series shows rapid improvement in iga and reduction inflammatory lesion count with oral sarecycline, and confirms previously reported significant improvement of truncal acne in phase 3 clinical trials ▪ sarecycline is an effective narrow-spectrum antibiotic alternative that can be utilized in treating truncal acne, especially when topical agents are challenging for the patients to apply due to surface area and location disclosures: research grant from almirall, llc. 1. del rosso jq, stein-gold l, lynde c, tanghetti e, alexis af. truncal acne: a neglected entity. j drugs dermatol. 2019;18(12):205-1208. 2. tan j, beissert s, cook-bolden f, et al. impact of facial and truncal acne on quality of life: a multi-country population-based survey. jaad international. 2021;3:102-110. doi:10.1016/j.jdin.2021.03.002 3. bunick cg, keri j, tanaka sk, et al. antibacterial mechanisms and efficacy of sarecycline in animal models of infection and inflammation. antibiotics (basel). 2021;10(4):439. doi:10.3390/antibiotics10040439 4. moore a, green lj, bruce s, et al. once-daily oral sarecycline 1.5 mg/kg/day is effective for moderate to severe acne vulgaris: results from two identically designed, phase 3, randomized, double-blind clinical trials. journal of drugs in dermatology : jdd. 2018;17(9):987-996. 5. del rosso jq, stein gold l, baldwin h, et al. management of truncal acne with oral sarecycline: pooled results from two phase-3 clinical trials. j drugs dermatol. 2021;20(6):634-640. doi:10.36849/jdd.2021.6204 https://doi.org/10.1016/j.jdin.2021.03.002 https://doi.org/10.3390/antibiotics10040439 https://doi.org/10.36849/jdd.2021.6204 skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 764 in-depth review eruptive keratoacanthoma in a 59-year-old female with chronic kidney disease: a case report and review of treatment approaches mitchell taylor, ba1,2, amelia pham, bs1,2, michaela clausen, bs1,2, kamruz darabi, md3,4 1 school of medicine, creighton university, omaha, ne 2 chi health creighton university medical center – bergan mercy, omaha, ne 3 department of dermatology, university of minnesota medical school, minneapolis, mn 4 darabi dermatology, waconia, mn keratoacanthoma (ka) is a low-grade tumor of the skin that appears as a rapidly growing, dome-shaped papule in sun-exposed areas of the body.1 clinically, kas may present as solitary or multiple lesions due to sporadic development, an underlying inherited syndrome, or in association with chronic inflammation.2 these lesions tend to develop with a rapid onset followed by relative tumor stability and eventual regression. the most common subtype presents as a single lesion with a central keratin-filled crater that may regress without intervention, though many are biopsied to rule out other diagnoses such as squamous cell carcinoma (scc), amelanotic melanoma, merkel cell carcinoma, and cutaneous infections.3, 4 despite many shared histological features between ka and scc, most authors regard ka as benign.5 however, due to the ambiguity and difficulty with histological differentiation between ka and invasive welldifferentiated scc, and sometimes only partial sampling techniques, current guidelines recommend surgical excision for kas to ensure treatment of potential malignancy.1 while the most common variants of kas manifest as sporadic and solitary lesions, a number of syndromes have been described in which individuals develop hundreds to thousands of kas.6 unlike solitary kas, multiple ka syndromes affect the skin regardless of sun exposure.7 although the mechanism of progression for multiple ka syndromes is poorly understood, risk factors are known to include a state of chronic injury, inflammation, or immunosuppression.6 abstract we present the case of a 59-year-old female with multiple squamous neoplasms, including keratoacanthomas, well-differentiated squamous cell carcinomas, and prurigo nodules. the patient developed dozens of lesions progressively over the course of a few years. keratoacanthomas can be challenging to distinguish from well-differentiated squamous cell carcinomas; this and the presence of numerous lesions poses a major challenge with diagnosing and managing this condition. the pathogenesis, challenges with diagnosis and management, and treatment regimens for eruptive keratoacanthomas are further discussed. introduction skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 765 multiple ka syndromes may be familial or sporadic and are classified into different subtypes based on specific disease criteria and characteristics. a correct diagnosis of multiple ka syndrome provides medical treatment options other than surgical methods used for conventional solitary kas and well-differentiated sccs and provides an opportunity to avoid surgical overtreatment of lesions. we report the case of a 59-year-old caucasian female who presented with a 5year history of disseminated skin lesion development on her upper and lower extremities, sparing the trunk, head, and neck associated with extreme pruritus (figure 1). her medical history was significant for a 4-year history of stage 4 chronic kidney disease as well as a 36-year history of type 2 diabetes mellitus. analysis of peripheral blood and serum biochemistry revealed a hemoglobin a1c of 5.8%, estimated glomerular filtration rate (egfr) of 22, creatinine of 2.37, and bun of 37. her social history consisted of 10+ pack years of tobacco use and 10+ years of daily alcohol consumption. the patient’s family history was noncontributory. figure 1. lesions on the upper and lower extremities. biopsies and excisions were taken for diagnostic and curative reasons. histopathology of the submitted specimens revealed two prurigo nodules on deep shave saucerizations (figure 2), three welldifferentiated sccs on deep shave saucerizations, ka-type sccs on two excisions (figure 3), and well-differentiated invasive scc on three excisions (figure 4). all specimens were examined by dermatopathologists. features of perforating diseases, such as collagen or elastic fiber degeneration and expulsion through the epidermis, were not seen in the submitted specimens. in light of the abundance of her lesions, further diagnostic workup was initiated to determine her risk of metastasis. one of the well-differentiated sccs was sent for molecular testing via decisiondx-scc. results of the test determined the patient to be in a class 1 category, which is associated with a low risk of metastasis within a 3-year period. figure 2. histopathology of prurigo nodule on deep shave saucerization. case report skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 766 figure 3. histopathology of excised ka-type scc at (a) 4x power and (b) 10x power. figure 4. histopathology of well-differentiated invasive scc on excision. skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 767 given the diffuse nature of her lesions, oral acitretin 25mg once daily was initiated. after three months of therapy, new lesions ceased to develop, and existing lesions decreased in size. however, the patient reported significant levels of pruritus and xerosis associated with acitretin, which led to the patient discontinuing acitretin. going forward, our plan is to begin intralesional triamcinolone acetonide injections once every four weeks in an attempt to alleviate pruritus associated with her lesions and potentially reduce the possibility of overlapping reactive epithelial changes leading to prurigo nodularis-like lesions. the patient may also benefit from unna boot applications to help protect the lesions from manual trauma due to pruritus, also leading to reactive prurigo nodularis-like changes. unna boots may be combined with topical 5fluorouracil each week for a 4–6-week period to target the patient’s hyperplastic epithelial neoplasms (prurigo nodules, kas, welldifferentiated scc). the patient will continue to be carefully observed on a regular basis to monitor for development of high-grade squamous cell carcinomas with higher morbidity potential, requiring more aggressive surgical treatment. kas may present as solitary or multiple lesions; multiple kas can be further divided into the ferguson-smith and grzybowski’s eruptive ka syndromes.8 ferguson-smith syndrome is an autosomal dominant variant of multiple ka syndrome seen predominantly in individuals of scottish descent.6 these patients present during adolescence with multiple kas that tend to spontaneously regress, resulting in the formation of an atrophic scar. the other form of multiple ka syndrome, grzybowski’s eruptive ka (geka), was first described by gzrybowski in 1950 and published under the title “a case of peculiar generalized epithelial tumors of the skin”.9 this particular variant of multiple ka syndrome is sporadic and characterized by some (see below) as an abrupt or progressive development of hundreds to thousands of small 0.5cm to 1cm kas during the fifth to seventh decade of life on the torse and extremities, sometimes involving the palms, soles, genitals, and mucous membranes of the lips and eyelids.10 despite continued reports of new geka cases since its discovery in 1950, the medical community has failed to establish a definitive set of diagnostic criteria for the condition.9 nofal et al. have proposed the following as potential criteria for geka diagnosis: generalized eruption of multiple welldemarcated papules with some having a keratotic center, lack of family history, onset in adulthood (most often fifth to seventh decade), and severe and persistent pruritus. variable features include the presence of mucosal lesions, masked facies, and ectropion. some of our patient’s presentation, such as histological findings of kas, late onset of presentation during the fifth decade of life, lack of family history, and severe pruritus all point to a diagnosis of geka. other characteristics of our patient favor the diagnosis of eruptive squamous atypia (esa), given her lesions were confined to her extremities, accessible to picking and koebnerization, and some lesions not meeting diagnostic criteria for kas and showing features of prurigo nodules and well-differentiated sccs.11 in real-life clinical settings, many patients present with overlap features of entities with multiple generalized kas, and this contributes to the difficulty in the literature to consistently define geka. therefore, we propose our patient may have overlapping features of geka and esa. the distinction may only be of discussion skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 768 academic interest as the treatment approaches are similar. a unique challenge of managing geka/esa is differentiating clinical and histological features of well-differentiated scc (that require surgical intervention) from multiple eruptive kas and reactive hyperplasia and atypia as a result of chronic scratching and picking (that require more conservative treatment approaches). in practice, to distinguish a true neoplastic carcinoma from a low-grade generalized ka or reactive squamous proliferation, clinicians often rely on clinical features such as duration, morphology, and growth rate.12 while this information can be helpful, studies suggest that these features are extremely variable and unreliable as diagnostic criteria. histopathology and distinctive microscopic criteria, mainly architectural silhouette of completely excised lesions and degree of epithelial atypia, have been proposed in distinguishing between kas/reactive squamous proliferations and welldifferentiated sccs on the other side. in spite of these suggested criteria, differentiating the two histologically continues to be a challenge due to shared silhouette, cytology, and architectural growth patterns.13 a study conducted by criber et al. examining pathology features of 296 ka and scc found that the criteria historically used to differentiate these lesions is unreliable.12 they observed that the 5 most useful criteria in distinguishing between kas (epithelial lip, sharp outline between tumor and stroma) and sccs (ulceration within the tumor, numerous mitoses, marked pleomorphism) did not significantly increase the sensitivity and specificity of a histological diagnosis. while recent studies have shown potential in differentiating sccs from kas using apoptotic and cell adhesion markers, further research is necessary before such techniques can be implemented into clinical practice.14 the biopsy method has also been observed to affect the diagnosis of ka versus scc. according to popkin et al., biopsy specimens obtained via shave, partial punch, or piececut provide inadequate tissue for a pathologist to examine when suspecting a diagnosis of ka.15 the downfall to these methods is the inability to consistently obtain the base or overall architectural silhouette of the lesion. this increases the possibilities of overlooking a more aggressive and invasive growth pattern. therefore, a fusiform sample obtained via scalpel excision is regarded as the recommended technique when suspecting ka. as the majority of our patient’s biopsies were obtained via shave and saucerization, we question the degree to which kas may have been misdiagnosed as sccs. as a result, individuals like our patient presenting with geka/esa overlap features may have biopsy reports indicating both kas and well-differentiated sccs.5, 8 a variety of systemic and topical agents have been explored in the treatment of geka and esa, but none are considered to be satisfactory.16 for singular kas, treatment via surgical excision or other physical modalities including cryotherapy, laser ablation, and curettage have been well described. topical agents such as 5-fluorouracil, tretinoin, imiquimod, bleomycin, and methotrexate have also been utilized. however, some of these methods pose challenging to use in geka and esa due to the diffuse nature of lesions in these patients. therefore, systemic therapy represents the most practical approach in management of geka and esa.9, 17 oral retinoids such as isotretinoin and acitretin are proposed as first-line agents, although response to these medications is variable. our patient responded well to a three-month trial of 25 skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 769 mg acitretin, where her lesions decreased in size and no new lesions were noted. however, the response to systemic retinoids in geka and esa patients is incredibly variable; some patients experience minimal or no improvement following treatment.18 because our patient became non-adherent to systemic retinoids due to side effects, treatment with intralesional triamcinolone acetonide and weekly application of an unna boot combined with topical 5-fluorouracil cream until achieving treatment goal were discussed. sanders et al. reported a case in which treatment with intralesional triamcinolone acetonide in a geka patient resulted in complete clearance of lesions and minimal scarring within 2-4 weeks.19 compared to intralesional methotrexate and 5-fluorouracil, which are both commonly used in practice, intralesional triamcinolone acetonide holds the benefit of immediately reducing inflammation and itching in the patient. advocates of intralesional triamcinolone acetonide believe eruptive kas are reactive in nature and due to low-grade cutaneous injury or inflammation.20 supplemental weekly treatment with topical 5-fluorouracil wrapped with an unna boot has also shown to be effective for inducing ka regression.20, 21 use of an unna boot containing zinc oxide further reduces inflammation, promotes healing, and provides a physical barrier to prevent further trauma inflicted by the patient scratching intensely itchy lesions and thereby potentially perpetuating lesions or contributing to reactive changes such as prurigo nodules and reactive squamous hyperplasia.20 this case describes a 59-year-old female with generalized kas, prurigo nodules, and well-differentiated sccs on her extremities, demonstrating characteristic features of geka and esa. because kas and welldifferentiated sccs have similar clinical and histologic features, it is often a challenge to diagnostically distinguish the two. while three months of oral acitretin therapy was mildly effective in our patient, adherence to treatment was inconsistent due to intolerable xerosis and worsening pruritus. our treatment plan moving forward will include continued systemic therapy with acitretin at a reduced dose of 12.5 mg daily, intralesional triamcinolone acetonide every four weeks, and weekly topical 5% fluorouracil covered by an unna boot on one leg at a time for 4-6 weeks. with our patient’s comorbidities of diabetes and chronic kidney disease, we plan to monitor complete blood count (cbc), renal function, blood glucose, and fasting lipid profile throughout treatment. patient consent: consent for the publication of recognizable patient photographs or other identifiable material was obtained by the authors and included at the time of article submission to the journal stating that all patients gave consent with the understanding that this information may be publicly available. conflict of interest disclosures: none funding: none corresponding author: mitchell taylor, ba 3920 dewey ave, omaha, ne 68105 phone: 612-356-0360 email: mat96996@creighton.edu references: 1. tisack a, fotouhi a, fidai c, friedman bj, ozog d, veenstra j. a clinical and biological review of keratoacanthoma. british journal of dermatology (1951). 2021;185(3):487-498. doi: 10.1111/bjd.20389. 2. ko cj, md. keratoacanthoma: facts and controversies. clinics in dermatology. 2010;28(3):254-261. doi: 10.1016/j.clindermatol.2009.06.010. 3. ghadially f. the role of the hair follicle in the origin and evolution of some cutaneous conclusion skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 770 neoplasms of man and experimental animals. cancer. 1961;14(4):801-816. doi: 10.1002/10970142(199007/08)14:43.0.co;2-k. 4. calonje e, mckee ph. mckee's pathology of the skin. fifth edition ed. ; 2020. 5. havenith r, de vos l, fröhlich a, et al. grzybowski’s generalized eruptive keratoacanthomas in a patient with terminal kidney disease—an unmet medical need equally ameliorated by topical imiquimod cream and lapacho tea wraps: a case report. dermatol ther (heidelb). 2021;11(2):625-638. doi: 10.1007/s13555021-00502-2. 6. kwiek, bartlomiej, md, phd, schwartz, robert a., md, mph. keratoacanthoma (ka): an update and review. journal of the american academy of dermatology. 2015;74(6):1220-1233. doi: 10.1016/j.jaad.2015.11.033. 7. mascitti h, de masson a, brunet-possenti f, et al. successful treatment of generalized eruptive keratoacanthoma of grzybowski with acitretin. dermatol ther (heidelb). 2019;9(2):383-388. doi: 10.1007/s13555019-0287-0. 8. yell ja. grzybowski's generalized eruptive keratoacanthoma. journal of the royal society of medicine. 1991;84:170-171. 9. nofal a, assaf m, nofal e, alradi m. generalized eruptive keratoacanthoma: proposed diagnostic criteria and therapeutic evaluation. journal of the european academy of dermatology and venereology. 2014;28(4):397-404. doi: 10.1111/jdv.12226. 10. consigli je, gonzalez me, morsino r, et al. generalized eruptive keratoacanthoma (grzybowski variant). british journal of dermatology (1951). 2000;142(4):800-803. doi: 10.1046/j.1365-2133.2000.03430.x. 11. que skt, compton la, schmults cd. eruptive squamous atypia (also known as eruptive keratoacanthoma): definition of the disease entity and successful management via intralesional 5-fluorouracil. journal of the american academy of dermatology. 2019;81(1):111-122. doi: 10.1016/j.jaad.2018.10.014. 12. cribier b, asch p, grosshans e. differentiating squamous cell carcinoma from keratoacanthoma using histopathological criteria: is it possible? a study of 296 cases. dermatology (basel). 1999;199(3):208-212. 13. kossard s, tan k, choy c. keratoacanthoma and infundibulocystic squamous cell carcinoma. the american journal of dermatopathology. 2008;30(2):127134. doi: 10.1097/dad.0b013e318161310c. 14. slater m, barden ja. differentiating keratoacanthoma from squamous cell carcinoma by the use of apoptotic and cell adhesion markers. histopathology. 2005;47(2):170-178. doi: 10.1111/j.13652559.2005.02155.x. 15. popkin gl, brodie sj, hyman ab, andrade r, kopf aw. a technique of biopsy recommended for keratoacanthomas. archives of dermatology (1960). 1966;94(2):191-193. doi: 10.1001/archderm.1966.01600260083010. 16. nofal a, assaf m, ghonemy s, nofal e, yosef a. generalized eruptive keratoacanthoma: a diagnostic and therapeutic challenge. international journal of dermatology. 2015;54(2):160-167. doi: 10.1111/ijd.12308. 17. clark ma, guitart j, gerami p, marks br, amin s, yoo ss. eruptive keratoacanthomatous atypical squamous proliferations (kasps) arising in skin graft sites. jaad case reports. 2015;1(5):274276. doi: 10.1016/j.jdcr.2015.06.009. 18. street ml, white jw, gibson le. multiple keratoacanthomas treated with oral retinoids. journal of the american academy of dermatology. 1990;23(5):862-866. doi: 10.1016/0190-9622(90)70305-2. 19. sanders s, busam kj, halpern ac, nehal ks. intralesional corticosteroid treatment of multiple eruptive keratoacanthomas: case report and review of a controversial therapy. dermatologic surgery. 2002;28(10):954-958. doi: 10.1046/j.15244725.2002.02069.x. 20. west l, ayoade k, vandergriff t, nijhawan ri. multiple reactive keratoacanthomas treated with zinc oxide wraps and intralesional corticosteroids. jaad case reports. 2018;4(7):701-704. doi: 10.1016/j.jdcr.2018.06.005. 21. gray rj, meland nb. topical 5-fluorouracil as primary therapy for keratoacanthoma. annals of plastic surgery. 2000;44(1):82-85. doi: 10.1097/00000637-200044010-00015. powerpoint presentation attitudes of patients with cutaneous melanoma towards prognostic testing using gene expression profiling background ›the 31-gene expression profile (31-gep) test for cutaneous melanoma (cm) assesses gene expression measurements from formalin-fixed paraffin-embedded primary tumor tissue to predict risk of tumor recurrence or metastasis. ›the 31-gep stratifies risk into one of three risk categories: low risk (class 1a), intermediate risk (class 1b/2a), and high risk (class 2b) and has been validated in multiple prospective and retrospective studies1-7. presented at 2022 winter clinical dermatology conference; january 14-19, 2022. lorrie-beth miley1, kelli ahmed phd2, jennifer j. siegel phd2, sonia k. morgan-linnell phd2, kyleigh lipira1 1.melanoma research foundation; washington, dc, usa; 2. castle biosciences, inc. friendswood, texas objective ›understand patients’ perspectives on prognostic and 31-gep testing and whether patients experience decision regret after having 31-gep testing performed. table 1. participant demographics methods ›a 43-question online survey was distributed by the melanoma research foundation from june 14, 2021, through august 2, 2021. ›patients were asked a series of five validated questions that gauge patients’ level of regret regarding the decision to undergo 31-gep testing and the extent to which they experienced decision regret8-9, which was scored on a scale of 1–5, 1 being no regret, 5 being high regret, and 3 neutral. responses were limited to those self-reporting a melanoma diagnosis in or after 2014 (n=120), at which time 31-gep prognostic testing became available. demographics (n=120) total, n (%) tested, n not tested, n unknown, n gender male 19 (24.2%) 6 23 -female 90 (75%) 22 68 -prefer not to share 1 (0.8%) 0 1 -did you have decisiondx testing? yes 28 (23.3%) no 75 (62.5%) unsure 17 (14.2%) insurance coverage commercial 84 (73.7%) 22 55 7 commercial with medadvantage 6 (5.3%) 2 4 0 medicare 21 (18.4%) 3 12 6 none 1 (0.9%) 0 1 0 i don’t know 2 (1.8%) 0 1 1 results figure 1. did you want prognostic testing at the time of your diagnosis? respondents were asked if they wanted prognostic information about their tumor at the time of diagnosis. most respondents, whether they received 31gep or not, desired prognostic testing about their tumor. acknowledgments & disclosures references › this study was sponsored by castle biosciences, inc. › ka, jjs, and skm are employees and shareholders of castle biosciences, inc. lm and kl have no conflicts of interest. 1. lawson dh cr. continued evaluation of a 31-gene expression profile test (gep) for prediction of distant metastasis (dm) in cutaneous melanoma (cm). j clin oncol. 2015;33(15_suppl):9066. 2. ferris lk, farberg as, middlebrook b, johnson ce, lassen n, oelschlager km, et al. identification of high-risk cutaneous melanoma tumors is improved when combining the online american joint committee on cancer individualized melanoma patient outcome prediction tool with a 31-gene expression profile-based classification. j am acad dermatol. 2017 may;76(5):818-825.e3. 3. dillon ld, gadzia je, davidson rs, mcphee m, covington kr, cook rw, et al. prospective, multicenter clinical impact evaluation of a 31-gene expression profile test for management of melanoma patients. skin j cutan med. 2018 mar;2(2):111–21. 4. greenhaw bn. estimation of prognosis in invasive melanoma using a gene expression profile test. in 2016. 5. keller j, schwartz tl, lizalek jm, chang e, patel ad, hurley my, et al. prospective validation of the prognostic 31‐gene expression profiling test in primary cutaneous melanoma. cancer med. 2019 may;8(5):2205–12. 6. podlipnik s, carrera c, boada a, richarz na, lópez-estebaranz jl, pinedo-moraleda f, et al. early outcome of a 31-gene expression profile test in 86 ajcc stage ib-ii melanoma patients. a prospective multicentre cohort study. j eur acad dermatol venereol jeadv. 2019 may;33(5):857–62. 7. hsueh ec, debloom jr, lee jh, sussman jj, covington kr, caruso hg, et al. long-term outcomes in a multicenter, prospective cohort evaluating the prognostic 31-gene expression profile for cutaneous melanoma. jco precis oncol [internet]. 2021 apr 6 [cited 2021 apr 6]; available from: https://ascopubs.org/doi/pdf/10.1200/po.20.00119 8. brehaut jc, o’connor am, wood tj, hack tf, siminoff l, gordon e, et al. validation of a decision regret scale. med decis making. 2003 jul;23(4):281–92. 9. am o. user manual decision regret scale [internet]. 1996 [cited 2020 sep 29]. available from: https://decisionaid.ohri.ca/docs/develop/user_manuals/um_regret_scale.pdf. ›90% of patients wanted prognostic information about their tumors at the time of diagnosis. ›patients wanted 31-gep testing to increase their knowledge about their disease (76.9%) and inform treatment decisions (46.2%). ›patients (>90%) felt 31-gep testing was useful and felt they gained understanding (60.7%) and relief from uncertainty (39.3%). ›patients receiving 31-gep results did not experience decision regret, even among patients who had class 2, high-risk tumors conclusions figure 5. decision regret scores respondents were asked a validated series questions regarding the level of regret they experienced with their decision to undergo 31-gep testing. blue (class 1) and orange (class 2) circles represent the mean decision regret score for each respondent. the dashed line indicates decision regret (3.05). median decision regret scores for all class 1 or class 2 respondents (red circles) were not significantly different (p=0.058). both class 1 (p<0.001) and class 2 (p=0.036) median decision regret scores were significantly below the decision regret line, indicating no or little regret regardless of high or low risk results. *, statistically significant; n.s., not significant *p < 0 .0 0 1 *p = 0 .0 3 6 n.s., p=0.058 results figure 2. factors that influenced patients’ decisions to get 31-gep testing figure 4. benefits of 31-gep testing for patients respondents who received 31-gep testing were asked what factors impacted their decision to get 31-gep testing. respondents were allowed to select all choices that applied. the percent of respondents who selected a particular reason are shown. internally driven choices are indicated in blue; externally driven choices are indicated in orange. respondents who received 31-gep testing (n=24 responses) answered whether they felt that the results were useful. the graph indicates the number of respondents who chose a particular choice and their reported 31-gep class call. most patients thought the 31-gep was at least somewhat useful. respondents who received 31-gep testing were asked how they benefitted from their 31-gep test results. respondents were first asked to select all the benefits they felt they gained (select as many responses as applied), and the percent of respondents that selected a given choice are shown. ›participants who received 31-gep testing felt that the results were useful to them. testing game them increased knowledge, relief from uncertainty, personalized treatment options, and information for life planning. 0 20 40 60 80 100 increased knowledge and understanding relief from uncertainty about future more personalized treatment options information relevant to life planning other not useful percent of respondents figure 3. utility of 31-gep test information 0 20 40 60 80 100 my health care provider recommended it a friend or family member recommended it i wanted to get all information i could about my melanoma i wanted to better understand my future i thought it would better inform my treatment options percent of respondents skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 260 short communication step 1 as pass/fail: navigating dermatology application components as holistic review expands albert g. wu ms1, abigail cline, phd md2, marian russo, md2 1 new york medical college school of medicine, valhalla, ny 2 department of dermatology, metropolitan hospital, new york, ny historically one of the most competitive specialties, dermatology saw only 82.9% of us md seniors successfully matching into the specialty in 2022 (national average = 92.9%)1. the 2022-2023 application cycle will be the first where applicants may have their step 1 scores listed as “pass/fail“ rather than numerically. in an attempt to clarify how the step scoring representation change could shift appliation evaluation, we sent a 53-question survey via email to dermatology program directors (pds) to evaluate the importance of 26 application aspects. respondents were asked to rate these aspects on a 1-5 likert scale (1= not all important to 5= extremely important), as well as how its importance would be affected, if at all, by step 1 becoming pass/fail. respondents predicted that longitudinal methods of candidate evaluation such as letters of recommendation, away rotations, and medical school transcripts, would increase in importance after the score change, while criteria most likely to become less important included usmle step 1 and usmle step 2 scores (table 1). as the number of applicants to dermatology continues to increase, residency programs have been developing methods of holistic evaluation, including considering a candidate‘s journey to dermatology, professional goals, and volunteerism, in additional to traditional metrics of exam scores, academic record, and publication total. 2 in the most recent appliation cycle, the association of professors of dermatology (apd) approved implementation of a supplemental application and preference signalling in an effort to give applicants more tools to represent themselves3. these additions represent an effort by programs to more clearly understand each applicant, even in the wake of rising application numbers and the logistical constraints of reviewing each one. therefore, students should take the time to throughly explore their motivations and passions for going into the field, so they can clearly represent themselves. hopefully, this journey would bring applicants into contact with mentors and professionals who are able to offer guidance and support, while creating meaningful experiences for residency programs to look to to better understand candidates. these may still create barriers for many individuals, including those without a home institution dermatology program, those lacking mentors4, or those unable to find opporunities to explore their interest in the field. skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 261 table 1. ranking of anticipated importance of survey items by mean response (n=26) survey categories evaluated items importance (out of 5) predicted change applicant characteristics letters of recommendation 4.58 more important honors in rotations 4.23 more important medical school transcript 4.12 more important dean's letter 3.77 more important extracurricular activities 3.69 no change rotation at your program 3.69 more important personal statement 3.65 more important scholastic work other awards/honors 3.62 more important usmle step 1 score 3.38 no change number of publications 3.35 more important usmle step 2 score 3.27 less important oral presentations 3.00 no change poster presentations 3.00 no change telephone call on behalf of applicant 2.96 more important alpha omega alpha (aoa) membership 2.92 no change other degrees (mph, mba, ms, phd) 2.85 no change previous application 2.73 no change applicant's medical school 2.73 no change research fellowships 2.62 no change applicant reputation previous residency 2.50 no change race 2.31 no change applicant's graduate institution (other than medical school) 2.15 no change applicant's undergraduate institution 2.08 no change personal appearance 1.96 no change age 1.38 no change gender 1.31 no change even with these changes, there are still signficantly more applicants than residency spots. an arms race is being waged within the objective measures of the application, most prominently in research publications5, the average for which has increased over 300% since 2007and while other metrics such as volunteer and work experiences have not increased significantly6, dermatology applicants were above the national average in every matched applicant characteristic published by the 2020 nrmp charting the outcomes of the match report. qualititative measures, including away rotations, interviews, and letters of recommendation, as well as longitudinal measures of academic and clinical performance, may be the most practical way for programs to evaluate a candidate’s fit for their philosopy, goals, and values. conflict of interest disclosures: none funding: none corresponding author: albert g. wu new york medical college school of medicine 40 sunshine cottage rd valhalla, ny 10595 email: awu4@student.nymc.edu references: mailto:awu4@student.nymc.edu skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 262 1. https://www.nrmp.org/wpcontent/uploads/2022/03/2022-match-by-thenumbers-final.pdf 2. luke, j., cornelius, l., & lim, h. w. (2021). dermatology resident selection: shifting toward holistic review? journal of the american academy of dermatology, 84(4), 1208–1209. doi:10.1016/j.jaad.2020.11.025 3. apd statement for 2020-2021 application cycle. penn dermatology residents. (2020, june 3). retrieved from https://dermatology.upenn.edu/residents/apdstatement/ 4. fernandez jm, behbahani s, marsch af. a guide for medical students and trainees to find virtual mentorship in the covid era and beyond. j am acad dermatol. 2021 may;84(5):e245e248. doi: 10.1016/j.jaad.2020.12.075. epub 2021 jan 10. pmid: 33440219. 5. ezekor m, pona a, cline a, huang ww, feldman sr. an increasing trend in the number of publications and research projects among dermatology residency applicants. j am acad dermatol. 2020 jul;83(1):214-216. doi: 10.1016/j.jaad.2019.09.021. epub 2019 sep 19. pmid: 31541752. 6. atluri s, seivright jr, shi vy, hsiao jl. volunteer and work experiences among dermatology residency applicants. j am acad dermatol. 2021 feb;84(2):e97-e98. doi: 10.1016/j.jaad.2020.08.134. epub 2020 sep 30. pmid: 33007333. skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 162 brief article a diagnostic challenge: desmoplastic melanoma katie a. o’connell, bs1, ryan m. svoboda, md, ms2, bryan e. anderson, md2, klaus f. helm, md2, kimberly m. ken, md2 1 school of medicine, eastern virginia medical school, norfolk, va 2 penn state college of medicine, department of dermatology, penn state milton s. hershey medical center, pa desmoplastic melanoma (dm) is uncommon, accounting for <4% of new melanoma diagnoses.1 clinically, dm is non-specific, often presenting as an amelanotic, fleshcolored nodule or plaque that clinically resembles a scar. dm can mimic both benign and malignant entities, with reports of dm presenting clinically as a neurofibroma, fibrous inflammatory hyperplasia, and sarcoma, among others.2 dm is most commonly located on sunexposed skin and is more frequent in males and older individuals, with a mean age of 70 years at diagnosis.3 on average, dm tends to be more deeply infiltrative than superficial spreading and lentigo maligna melanoma at the time of diagnosis—a feature which may be related to diagnostic delay and/or differences in tumor biology.1,3 a 60-year-old male with a history of basal cell carcinoma presented for evaluation of an indurated, slowly expanding, 1 cm skincolored, depressed plaque of the right forehead. the lesion exhibited rolled borders with mild associated follicular dropout around the periphery (figure 1). the lesion was otherwise asymptomatic, and the patient denied any history of trauma to the area. a 4mm punch biopsy of the rolled border was performed, which revealed thickened collagen bundles with underlying spindle cells arranged parallel to the epidermis, overall felt to be consistent with scar (figure 2). due to the lack of obvious inciting trauma in the patient’s history, the persistent clinical concern, and one focal area of fibromyxoidlike stroma identified in the punch biopsy abstract desmoplastic melanoma (dm) is uncommon and can be a diagnostic challenge both clinically and histologically. we report a unique presentation of dm presenting as an amelanotic, depressed, indurated plaque on the forehead. the lesion was clinically concerning for a morpheaform basal cell carcinoma and with an unrevealing initial punch biopsy, an excisional biopsy with immunohistochemistry was necessary to determine a diagnosis of pure desmoplastic melanoma. when a patient presents with a depressed, indurated plaque of unknown etiology, including dm in the clinical differential diagnosis and communicating this to the dermatopathologist can potentially reduce the risk for a delay in diagnosis. introduction case report skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 163 figure 1. a 1 cm, skin-colored, depressed plaque of the right forehead. note the apparent decrease in follicular ostia of the skin surrounding the atrophic portion of the lesion specimen, an excisional biopsy was obtained to more definitively rule out morpheaform basal cell carcinoma. histopathology revealed focal epidermal atrophy with an increased number of underlying parallel spindle cells and a superficial and deep lymphocytic infiltrate. sox-10, melan-a, and s-100 staining were performed and highlighted an increased number of cells in the basal layer as well as a focal proliferation of underlying spindle cells within the dermis (fig. 3, s-100 staining not shown). the histopathology was consistent with a pure desmoplastic melanoma, with a breslow depth of 1.3 mm. due to the fact that the lesion extended to within 1-2 mm of the peripheral margins of the excisional biopsy specimen, the patient was referred to our multidisciplinary skin and connective tissue oncology clinic for discussion of further workup and treatment. the patient underwent wide local excision of the area with 1cm margins without sentinel lymph node biopsy or advanced imaging. the patient continues to follow routinely in dermatology and has not exhibited any clinical evidence of recurrence or metastasis. histologically, dm is characterized by a paucicellular proliferation of spindled melanocytes accompanied by a densely fibrotic stroma and may closely resemble scar or other spindle cell tumors including atypical fibroxanthoma/pleomorphic dermal sarcoma, spindle cell squamous cell carcinoma (scc), and leiomyosarcoma.1 immunohistochemistry is essential to the diagnosis; s-100 is diffusely positive and markers of melanocytic differentiation such as melan-a and sox-10 are often positive but can be focally negative.1,4 the absence of staining for epithelial markers such as cytokeratins 5/6 and muscle markers such as smooth muscle actin and desmin help to differentiate dm from spindle scc and leiomyosarcoma, respectively. due to these challenges, a delay in diagnosis of dm is not uncommon, particularly if a partial biopsy is taken or if appropriate immunohistochemistry is not performed due to low clinical suspicion.4 there are two subtypes of dm—pure dm (pdm) and mixed dm (mdm)—named by the degree of desmoplasia.3 mixed dm arises from and thus resembles preexisting lesions of another melanoma subtype (often lentigo maligna melanoma).3 in contrast, pdm arises de novo.1,4 as with all melanoma, the mainstay of treatment is wide local excision with margins determined by breslow depth.1,5 compared to mdm, pdm exhibits a lower propensity for regional lymph node involvement, but a similar rate of distant metastasis, suggesting possible hematogenous spread.4 due to the lack of robust evidence, the utility of sentinel lymph node biopsy (slnb) for patients with pdm remains controversial.5 in cases of mdm, slnb should be considered based on tumor stage as is done for conventional melanoma.5 although adjuvant radiation therapy is rarely used in the treatment of discussion skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 164 figure 2. punch biopsy revealing dense collagen bundles with focally increased dermal spindle cells, parallel to the dermal-epidermal junction. a focal area of fibromyxoid-like stroma is seen (circled). hematoxylin-eosin stain (original magnification x2) figure 3. excisional biopsy revealing focal epidermal atrophy with increased underlying parallel spindle cells and a slightly desmoplastic stroma. melan-a stain reveals focal increase in basal layer melanocytes and also highlights dermal spindled cells. a) hematoxylin-eosin stain (original magnification x10) b) melan-a stain (original magnification x10). c) sox-10 stain (original magnification x10) melanoma, it may be considered for improved local control in cases of pdm exhibiting neurotropism, especially with positive surgical margins.5 this case highlights that dm can be a diagnostic challenge both clinically and histologically. it is important to consider desmoplastic melanoma as part of the differential diagnosis for scar-like lesions presenting in sun-exposed areas, particularly in the absence of prior surgery or trauma. conflict of interest disclosures: none funding: none corresponding author: ryan m. svoboda, md, ms conclusion a. b. c. skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 165 penn state college of medicine, hershey, pa. department of dermatology, penn state milton s. hershey medical center, pa telephone: (717)-531-6820 fax: (717)-531-4720 email: rsvoboda@pennstatehealth.psu.edu references: 1. nicolson ng, han d. desmoplastic melanoma. j surg oncol. 2019 jan;119(2):208-215. doi: 10.1002/jso.25317. epub 2018 nov 27. pmid: 30481377. 2. stokar e, rodriguez c, feldman j. desmoplastic melanoma masquerading as neurofibroma. cutis. 2021 may;107(5):258-260. doi: 10.12788/cutis.0241. pmid: 34288854. 3. pampena r, lai m, lombardi m, mirra m, raucci m, lallas a, apalla z, argenziano g, pellacani g, longo c. clinical and dermoscopic features associated with difficult-to-recognize variants of cutaneous melanoma: a systematic review. jama dermatol. 2020 apr 1;156(4):430-439. doi: 10.1001/jamadermatol.2019.4912. pmid: 32101255. 4. chen ll, jaimes n, barker ca, busam kj, marghoob aa. desmoplastic melanoma: a review. j am acad dermatol. 2013 may;68(5):825-33. doi: 10.1016/j.jaad.2012.10.041. epub 2012 dec 23. pmid: 23267722; pmcid: pmc4703041. 5. national comprehensive cancer network. melanoma: cutaneous (version 2.2021). [internet]. 2021 feb 19. available from: https://www.nccn.org/professionals/physician_gls/ pdf/cutaneous_melanoma.pdf. accessed may 14, 2021. https://www.nccn.org/professionals/physician_gls/pdf/cutaneous_melanoma.pdf https://www.nccn.org/professionals/physician_gls/pdf/cutaneous_melanoma.pdf skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 527 brief article numerous spider angiomas as the presenting sign of acute graft versus host disease shira lanyi, md1, abigail wills, md1, olivia schenck, md1 1 department of dermatology, university of virgina, charlottesville, va a 51-year-old caucasian male with a past medical history of acute lymphoblastic leukemia (all), status-post allogenic stem cell transplant and new-onset cytopenia concerning for relapse of all, presented to clinic for the new onset of a pruritic rash. the patient was being treated with methotrexate and inotuzumab, with his last cycle a month before the presentation of the rash. inotuzumab, an anti-cd22, is an immunotherapy agent for all. he was referred by hematology-oncology for biopsy of the rash which was not believed to be suggestive of gvhd. he stated that the rash developed within the past several months and continued to spread to his bilateral upper extremities, chest, and upper back. besides the mild pruritis, the patient had no other symptoms from the rash. he denied any history of liver disease, mucosal involvement, but had recently noticed melanotic stool. his most recent lft’s were within normal limits with an ast of 42 and an alt of 18. on physical exam, there were numerous, blanching spider telangiectasias on the bilateral arms, chest, abdomen, and upper back (figure 1 and 2). punch biopsy was performed on one of the lesions and triamcinolone 0.1% ointment was provided for symptomatic relief of pruritis. the final pathology report returned as acute gvhd. histologic sections of the punch biopsy from the right chest demonstrated a basket-weave stratum corneum and focal vacuolar interface changes of the basal layer of the epidermis and a hair follicle accompanied by satellite cell necrosis of basal keratinocytes. in the dermis there were ectatic superficial blood abstract graft versus host disease (gvhd) is a highly morbid immunologic reaction and complication commonly seen in response to allogenic hematopoietic stem cell transplant. the underlying pathophysiology of this reaction is due to donor t-lymphocyte migration and activation of the host’s innate immune system. quality of life is significantly impacted in these patients, particularly in those with chronic gvhd. gvhd may impact multiple organ systems, however, cutaneous involvement is the most common finding and is often the initial presenting sign. the clinical manifestations of cutaneous gvhd are highly variable, with many morphologies mimicking another skin condition. we present a rare case of a 51-year-old male with a past medical history of allogenic stem cell transplant, who presented with multiple spider hemangiomas over the chest and back. the patient had no past medical history of liver disease, and was subsequently diagnosed with biopsy-proven acute gvhd. case report skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 528 vessels and scattered interstitial lymphocytes. a gms failed to highlight fungal hyphae within the stratum corneum. these findings are consistent with a diagnosis of gvhd grade ii. figure 1. scattered telangiectasias on the upper back figure 2. dermatoscopic image of a single telangiectasia on the upper back graft versus host disease severely impacts the quality of life of patients after allogenic hematopoietic stem cell transplant (hsct) and carries a high risk of mortality with disease progression1,3,4. gvhd is a great challenge to the dermatologist, as its appearance often mimics many other dermatologic diseases3. gvhd is divided into acute and chronic forms. the nih classification divides acute gvhd into acute classic within 100 days of transplantation and late-onset acute gvhd. late-onset gvhd manifests after 100 days from transplantation with clinical features of classic acute gvhd. classic chronic gvhd presents with the clinical manifestations of chronic gvhd 100 days after transplantation. lastly, there is overlap syndrome in which features of both chronic and acute gvhd present at any time post-transplant2. the cutaneous manifestations of gvhd are often the presenting sign as well as the most common site for disease involvement1,3,4. the skin, liver, and gastrointestinal tract are the most commonly targeted organs overall1,. acute gvhd may present with the triad of diarrhea, elevated bilirubin, and cutaneous exanthema, however, there have been multiple case reports of isolated cutaneous findings1,3,4,7. erythematous maculopapular morbilliform eruptions are one of the more classically described findings of acute gvhd1,3. severe cases may progress to erythroderma and epidermolysis that resemble toxic epidermal necrolysis and may lead to confusion in diagnosis3. the exanthem is often pruritic but may also remain asymptomatic. less commonly found dermatologic findings in the literature include rashes that resemble acquired ichthyosis, pityriasis rubra pilaris, discussion skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 529 eczema-craquelé, and psoriasis vulgaris1,3,79,11. gu et al discuss a report of a patient with chronic gvhd and elevated lft’s that developed numerous spider hemangiomas on the upper extremities and trunk secondary to hepatic involvement and liver fibrosis following allogenic stem cell transplant. our patient was prescribed topical triamcinolone but was hospitalized due to worsening course of his leukemia and was lost to follow-up. as of the present, our case is the first report of multiple spider angiomas without signs of liver involvement in a patient with acute gvhd following allogenic stem cell transplant12. the differential diagnosis of a cutaneous eruption following stem cell transplant includes a viral exanthem, toxic erythema of chemotherapy, or a drug hypersensitivity reaction3,10. diagnosis of acute gvhd does not require a particular cutaneous finding, as the morphology can vary so vastly1,3,4,12. rather, the new onset of a skin rash with hepatic or gi involvement in the setting of a recent hsct, warrant further work-up and possible biopsy for gvhd1,3,10. microscopic features that are relatively specific for diagnosis include the presence of dermal eosinophils or dermal spongiosis1,3. a high degree of clinical suspicion is vital in the detection of unusual presentations of acute and chronic gvhd. we present a unique case of acute gvhd in which histological findings guided the final diagnosis. conflict of interest disclosures: none funding: none corresponding author: shira lanyi, md department of dermatology university of virginia 1221 lee st. 3rd floor charlottesville, va 22903 email: shira.lanyi@gmail.com references: 1. kavand s, lehman js, hashmi s, gibson le, elazhary ra. cutaneous manifestations of graftversus-host disease: role of the dermatologist. int j dermatol. 2017;56(2):131-140. doi:10.1111/ijd.13381 2. justiz vaillant aa, modi p, mohammadi o. graft versus host disease. in: statpearls. treasure island (fl): statpearls publishing; december 30, 2020. 3. strong rodrigues k, oliveira-ribeiro c, de abreu fiuza gomes s, knobler r. cutaneous graft-versus-host disease: diagnosis and treatment. am j clin dermatol. 2018 feb;19(1):33-50. doi: 10.1007/s40257-017-0306-9. pmid: 28656563; pmcid: pmc5797560. 4. ramachandran v, kolli ss, strowd lc. review of graft-versus-host disease. dermatol clin. 2019;37(4):569-582. doi:10.1016/j.det.2019.05.014 5. peñas pf, fernández-herrera j, garcía-diez a. dermatologic treatment of cutaneous graft versus host disease. am j clin dermatol. 2004;5(6):403-16. doi:10.2165/00128071-200405060-00005. pmid: 15663337. 6. wu pa, cowen ew. cutaneous graft-versus-host disease--clinical considerations and management. curr probl dermatol. 2012;43:101-15. doi: 10.1159/000335270. epub 2012 feb 17. pmid: 22377924; pmcid: pmc7458413. 7. hacisalihoglu up, sahin d. incidence, histopathological features and differential diagnosis of cutaneous graft versus host disease in allogeneic bone marrow transplantation. sisli etfal hastan tip bul. 2021 mar 17;55(1):68-75. doi: 10.14744/semb.2019.86729. pmid: 33935538; pmcid: pmc8085451. 8. byun hj, yang ji, kim bk, cho kh. clinical differentiation of acute cutaneous graft-versushost disease from drug hypersensitivity reactions. j am acad dermatol. 2011 oct;65(4):726-732. doi: 10.1016/j.jaad.2010.07.042. epub 2011 jun 8. pmid: 21641677. 9. wei j, zhang y, xu h, jin j, zhang j. atopic dermatitis-like presentation of graft-versus-host disease: a novel form of chronic cutaneous graftconclusion skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 530 versus-host disease. j am acad dermatol. 2013 jul;69(1):34-9. doi:10.1016/j.jaad.2012.12.970. epub 2013 feb 1. pmid: 23375455. 10. creamer d, martyn-simmons cl, osborne g, kenyon m, salisbury jr, devereux s, pagliuca a, ho ay, mufti gj, du vivier aw. eczematoid graft-vs-host disease: a novel form of chronic cutaneous graft-vs-host disease and its response to psoralen uv-a therapy. arch dermatol. 2007 sep;143(9):1157-62. doi: 10.1001/archderm.143.9.1157. pmid: 17875877. 11. gu y, li k, wu x, zhang jz. multiple spider angiomas in a patient with chronic hepatic graftversus-host disease. chin med j (engl). 2020;133(6):749-750. doi:10.1097/cm9.0000000000000707 12. ballester-sánchez r, navarro-mira m, sanzcaballer j, botella-estrada r. review of cutaneous graft-vs-host disease. actas dermosifiliogr. 2016;107(3):183-193. doi:10.1016/j.ad.2015.10.003 andrew blauvelt, md, mba,1 jacek c. szepietowski, md, phd, frcp (edin),2 kim papp, md, phd,3 eric l. simpson, md, mcr,4 jonathan i. silverberg, md, phd, mph,5 brian s. kim, md, mtr,6 shawn g. kwatra, md,7 michael e. kuligowski, md, phd, mba,8 may e. venturanza, md,8 kang sun, phd,8 leon kircik, md9 introduction ● atopic dermatitis (ad) is a highly pruritic, chronic, inflammatory skin disease1 ● itch is reported to be the most burdensome symptom of ad2; some patients with ad report itch every day3 – inadequate control of ad is associated with greater itch interference with daily living4 – the negative impact of itch in patients with ad highlights the need for achievement of an itch-free state ● janus kinases (jaks) play an important role in the pathogenesis of ad and the development of itch by mediating proinflammatory cytokines in skin and sensory neurons5,6 ● ruxolitinib cream is a topical formulation of ruxolitinib, a selective inhibitor of jak1 and jak27 ● in two phase 3 randomized studies of identical design (true-ad1 [nct03745638] and true-ad2 [nct03745651]), ruxolitinib cream demonstrated anti-inflammatory activity with rapid and sustained antipruritic action vs vehicle and was well tolerated in patients with ad7 objective ● to describe the effect of ruxolitinib cream on achievement of an itch-free state in adolescent and adult patients with ad using pooled data from two phase 3 trials methods study design and patients ● eligible patients were aged ≥12 years with ad for ≥2 years and had an investigator’s global assessment score of 2 or 3 and 3%–20% affected body surface area (excluding scalp) ● key exclusion criteria were unstable course of ad, other types of eczema, immunocompromised status, use of ad systemic therapies during the washout period and during the study, use of ad topical therapies (except bland emollients) during the washout period and during the study, and any serious illness or medical condition that could interfere with study conduct, interpretation of data, or patients’ well-being ● true-ad1 and true-ad2 had identical study designs (figure 1) – in both studies, patients were randomized (2:2:1) to 1 of 2 ruxolitinib cream strength regimens (0.75% twice daily [bid], 1.5% bid) or vehicle cream bid for 8 weeks of double-blinded treatment – patients on ruxolitinib cream subsequently continued treatment for 44 weeks; patients initially randomized to vehicle were rerandomized 1:1 (blinded) to either ruxolitinib cream regimen figure 1. study design • continuous treatment for 8 weeks • rescue treatment not permitted • treat as needed for 44 weeks • stop treatment 3 days after lesion clearance • rescue treatment not permitted vehicle-controlled period long-term safety period patients initially randomized to rux remain on their regimen patients on vehicle rerandomized 1:1 to 0.75% rux bid or 1.5% rux bid patients randomized 2:2:1 rux† visits every 4 weeks week 52day 1 week 8 recurrence of lesions clearance of lesions 1.5% rux bid (n=~240 in each study) 0.75% rux bid (n=~240 in each study) vehicle bid (n=~120 in each study) ad, atopic dermatitis; bid, twice daily; bsa, body surface area; rux, ruxolitinib cream. † patients self-evaluated recurrence of lesions between study visits and treated lesions with active ad (≤20% bsa). if lesions cleared between study visits, patients stopped treatment 3 days after lesion disappearance. if new lesions were extensive or appeared in new areas, patients contacted the investigator to determine if an unscheduled additional visit was needed. assessments ● the effects of ruxolitinib cream on itch were assessed by the proportion of patients achieving an itch numerical rating scale score of 0 or 1 (nrs 0/1) – patients were given an electronic diary to be completed each evening and were instructed to report their worst level of itch during the past 24-hour period from 0 (no itch) to 10 (worst imaginable itch) – the by-visit itch nrs score for post-baseline visits (weeks 2, 4, 8) was determined by averaging the 7 daily itch nrs scores before the study visit; if ≥4 daily scores were missing, the itch nrs score for the study visit was classified as missing ● the effects on eczema-related itch were also assessed using the proportion of patients reporting no days of itch per item 1 (frequency of itch; q1) of the patient-oriented eczema measure (poem)8 at baseline and weeks 2, 4, and 8 ● itch-free state was also assessed stratified by baseline itch nrs score (<6 or ≥6) statistical analyses ● all analyses were conducted using the pooled data from the vehicle-controlled portion of both studies ● the proportion of patients achieving itch nrs 0/1 and the number of days with no itch per poem q1 were assessed using logistic regression ● cumulative incidence plots were created for time to itch nrs 0/1 – a log-rank test was used for between-group comparisons ● the efficacy population consisted of 1208 patients (vehicle, n=244; 0.75% ruxolitinib cream, n=483; 1.5% ruxolitinib cream, n=481) results patients ● a total of 1249 patients (median age, 32 years) were randomized in the vc period ● the mean (sd) itch nrs score at baseline was 5.1 (2.4) ● distribution of baseline demographics and clinical characteristics was similar across treatment groups (table 1) table 1. patient demographics and baseline clinical characteristics characteristic vehicle (n=250) 0.75% rux (n=500) 1.5% rux (n=499) total (n=1249) age, median (range), y 34.0 (12–82) 33.0 (12–85) 31.0 (12–85) 32.0 (12–85) female, n (%) 159 (63.6) 304 (60.8) 308 (61.7) 771 (61.7) race, n (%) white 170 (68.0) 345 (69.0) 355 (71.1) 870 (69.7) black 61 (24.4) 118 (23.6) 113 (22.6) 292 (23.4) asian 10 (4.0) 16 (3.2) 20 (4.0) 46 (3.7) other 9 (3.6) 21 (4.2) 11 (2.2) 41 (3.3) region, n (%) north america 172 (68.8) 342 (68.4) 341 (68.3) 855 (68.5) europe 78 (31.2) 158 (31.6) 158 (31.7) 394 (31.5) bsa, mean (sd), % 9.6 (5.5) 10.0 (5.3) 9.6 (5.3) 9.8 (5.4) easi, mean (sd) 7.8 (4.8) 8.1 (4.9) 7.8 (4.8) 8.0 (4.8) iga, n (%) 2 64 (25.6) 125 (25.0) 123 (24.6) 312 (25.0) 3 186 (74.4) 375 (75.0) 376 (75.4) 937 (75.0) itch nrs score, mean (sd) 5.1 (2.4) 5.2 (2.4) 5.1 (2.5) 5.1 (2.4) baseline poem q1 (itch frequency) response, n (%)* no days 5 (2.1) 9 (1.9) 13 (2.8) 27 (2.3) 1–2 days 18 (7.5) 30 (6.3) 35 (7.4) 83 (7.0) 3–4 days 33 (13.8) 75 (15.8) 63 (13.3) 171 (14.4) 5–6 days 29 (12.1) 44 (9.3) 50 (10.6) 123 (10.4) every day 155 (64.6) 317 (66.7) 311 (65.9) 783 (66.0) duration of disease, median (range), y 16.5 (0.8–79.1) 15.1 (0.1–68.8) 16.1 (0–69.2) 15.8 (0–79.1) facial involvement, n (%)† 93 (37.2) 195 (39.0) 197 (39.5) 485 (38.8) number of flares in last 12 mo, mean (sd)† 7.3 (25.7) 5.2 (6.7) 6.0 (17.6) 5.9 (16.5) bsa, body surface area; easi, eczema area and severity index; iga, investigator’s global assessment; nrs, numerical rating scale; poem q1, patient-oriented eczema measure– question 1; rux, ruxolitinib cream. * data available for 1187 patients (vehicle, n=240; 0.75% rux, n=475; 1.5% rux, n=472). † patient reported. efficacy ● a significantly higher proportion of patients who applied 0.75% and 1.5% ruxolitinib cream achieved itch nrs 0/1 vs vehicle as early as day 2 (approximately 36 hours after first application; 19.1% and 22.3% for 0.75% and 1.5% ruxolitinib cream, respectively, vs 9.2%; both p<0.01; figure 2) figure 2. daily proportion of patients achieving itch nrs 0/1 in the first 7 days pr op or tio n of p at ie nt s ac hi ev in g itc h nr s 0/ 1, % 0 10 20 30 40 50 70 60 1 2 3 4 5 6 7 study day vehicle 0.75% rux 1.5% rux number of patients vehicle 0.75% rux 1.5% rux day 1 223 444 445 day 4 215 432 435 day 7 220 429 436 10.8 9.2 11.0 10.2 13.2 15.2 14.1 12.6 19.1 23.9 29.4 28.0 31.3 32.6 13.0 22.3 25.9 30.8 34.4 38.0 39.4 **** ** **** *** **** **** **** **** **** **** **** **** nrs, numerical rating scale; rux, ruxolitinib cream. ** p<0.01 vs vehicle; *** p<0.001 vs vehicle; **** p<0.0001 vs vehicle. ● at week 8, the proportion of patients achieving itch nrs 0/1 (average of daily nrs measurements over the 7 days before the week 8 visit) was significantly higher for patients who applied ruxolitinib cream (0.75%/1.5%) compared with vehicle (45.5%/51.5% vs 23.1%; both p<0.0001; figure 3) figure 3. proportion of patients achieving itch nrs 0/1 **** **** pr op or tio n (s e) o f p at ie nt s ac hi ev in g itc h nr s 0/ 1, % 0 10 20 30 40 50 70 60 2 4 8 time, wk vehicle 0.75% rux 1.5% rux number of patients vehicle 0.75% rux 1.5% rux 210 425 429 198 423 421 173 374 400 10.5 15.2 23.129.6 39.2 45.535.2 46.3 51.5 nrs, numerical rating scale; rux, ruxolitinib cream. **** p<0.0001 vs vehicle. ● median time to achieve the first observed day with itch nrs 0/1 was shorter for ruxolitinib cream (12.0 and 8.0 days for 0.75% and 1.5% ruxolitinib cream, respectively) vs vehicle (51.0 days; figure 4); cumulative incidence rates for achieving ≥1 day with itch nrs 0/1 were significantly higher for ruxolitinib cream (log-rank p<0.0001 [both]) figure 4. kaplan-meier curve of time to achieve itch nrs 0/1 vehicle censored number of patients vehicle 0.75% rux 1.5% rux pr ob ab ili ty o f ac hi ev in g itc h nr s 0/ 1 0.0 0.6 0.8 0 8015105 302520 454035 605550 757065 1.0 0.4 0.2 0.5 0.3 0.1 0.7 0.9 time to event, d 0.75% rux 1.5% rux 242 479 480 99 116 85 110 123 96 116 141 109 125 159 119 3 3 1 8 7 8 11 0 0 71 79 73 93 103 81 138 175 132 147 192 153 160 216 183 173 255 216 194 318 301 0 nrs, numerical rating scale; rux, ruxolitinib cream. ● significantly more patients reported no days of itch with ruxolitinib cream per poem q1 at week 8 (28.3% and 32.9% for 0.75% and 1.5% ruxolitinib cream, respectively) vs vehicle (9.0%; both p<0.0001; figure 5) figure 5. patients reporting no days of itch per poem q1 pr op or tio n (s e) o f p at ie nt s re po rti ng n o da ys o f i tc h pe r p oe m q 1, % 0 10 20 30 40 50 70 60 2 4 8 time, wk vehicle 0.75% rux 1.5% rux number of patients vehicle 0.75% rux 1.5% rux 224 455 455 209 453 459 200 427 444 4.5 5.7 9.0 18.0 23.0 28.3 23.1 29.0 32.9 **** **** poem q1, patient-oriented eczema measure–question 1; rux, ruxolitinib cream. **** p<0.0001 vs vehicle. ● as assessed by itch nrs 0/1 or poem, more patients achieved itch-free status at week 8 with ruxolitinib cream vs vehicle (47.7% and 52.0% for 0.75% and 1.5% ruxolitinib cream, respectively, vs 23.4%; both p<0.0001; figure 6) regardless of baseline itch score (figure 7) figure 6. patients achieving itch nrs 0/1 or no days of itch per poem q1 pr op or tio n (s e) o f p at ie nt s ac hi ev in g itc h nr s 0/ 1 or n o da ys o f i tc h pe r p oe m q 1, % time, wk vehicle 0.75% rux 1.5% rux number of patients vehicle 0.75% rux 1.5% rux 226 461 461 212 456 462 201 432 450 0 10 20 30 40 50 60 70 2 4 8 11.5 15.6 23.4 33.0 41.4 47.738.6 48.7 52.0 **** **** nrs, numerical rating scale; poem q1, patient-oriented eczema measure–question 1; rux, ruxolitinib cream. **** p<0.0001 vs vehicle. figure 7. patients achieving itch nrs 0/1 or no days of itch per poem q1 by baseline itch nrs score pr op or tio n (s e) o f p at ie nt s ac hi ev in g itc h nr s 0/ 1 or n o da ys o f i tc h pe r p oe m q 1, % time, wk baseline itch nrs <6 baseline itch nrs ≥6 vehicle 0.75% rux 1.5% rux number of patients vehicle 0.75% rux 1.5% rux 122 258 270 113 257 276 109 249 265 0 10 20 30 40 50 60 70 2 4 8 16.4 22.1 27.5 44.6 48.6 57.4 47.8 55.1 58.1 **** **** pr op or tio n (s e) o f p at ie nt s ac hi ev in g itc h nr s 0/ 1 or n o da ys o f i tc h pe r p oe m q 1, % time, wk vehicle 0.75% rux 1.5% rux number of patients vehicle 0.75% rux 1.5% rux 90 176 172 86 170 168 79 158 167 0 10 20 30 40 50 60 70 2 4 8 4.4 5.8 17.716.5 32.4 34.225.0 38.7 41.3 *** ** nrs, numerical rating scale; poem q1, patient-oriented eczema measure–question 1; rux, ruxolitinib cream. ** p<0.01 vs vehicle; *** p<0.001 vs vehicle; **** p<0.0001 vs vehicle. safety ● ruxolitinib cream was well tolerated with an adverse event (ae) profile similar to vehicle7; no serious aes were related to ruxolitinib cream conclusions ● a significantly greater number of patients treated with ruxolitinib cream achieved and sustained an itch-free state vs vehicle during the 8-week treatment period ● patients who applied ruxolitinib cream had a substantially shorter median time to itch nrs 0/1 vs vehicle disclosures ab has served as a scientific advisor and/or clinical study investigator for abbvie, abcentra, aligos, almirall, amgen, arcutis, arena, aslan, athenex, boehringer ingelheim, bristol myers squibb, dermavant, eli lilly and company, evommune, forte, galderma, incyte corporation, janssen, landos, leo pharma, novartis, pfizer, rapt, regeneron, sanofi genzyme, sun pharma, and ucb pharma. jcs has served as an advisor for abbvie, leo pharma, menlo therapeutics, novartis, pierre fabre, and trevi; has received speaker honoraria from abbvie, eli lilly, janssencilag, leo pharma, novartis, sanofi genzyme, and sun pharma; and has received clinical trial funding from abbvie, almirall, amgen, galapagos, holm, incyte corporation, inflarx, janssencilag, menlo therapeutics, merck, novartis, pfizer, regeneron, trevi, and ucb. kp has received honoraria or clinical research grants as a consultant, speaker, scientific officer, advisory board member, and/or steering committee member for abbvie, akros, amgen, anacor, arcutis, astellas, bausch health/valeant, baxalta, boehringer ingelheim, bristol myers squibb, can-fite, celgene, coherus, dermira, dow pharmaceuticals, eli lilly, galderma, gilead, glaxosmithkline, incyte corporation, inflarx, janssen, kyowa hakko kirin, leo pharma, meiji seika pharma, merck (msd), merck serono, mitsubishi pharma, moberg pharma, novartis, pfizer, prcl research, regeneron, roche, sanofi-aventis/genzyme, sun pharmaceuticals, takeda, and ucb. els is an investigator for abbvie, eli lilly, galderma, kyowa hakko kirin, leo pharma, merck, pfizer, and regeneron and is a consultant with honorarium for abbvie, eli lilly, forte bio, galderma, incyte corporation, leo pharma, menlo therapeutics, novartis, pfizer, regeneron, sanofi genzyme, and valeant. jis received honoraria for advisory board, speaker, and consultant services from abbvie, asana, bluefin, boehringer ingelheim, celgene, dermavant, dermira, eli lilly, galderma, glaxosmithkline, glenmark, incyte corporation, kiniksa, leo pharma, menlo therapeutics, novartis, pfizer, realm, regeneron, and sanofi and research grants for investigator services from galderma and glaxosmithkline. bsk has served as a consultant to abbvie, almirall, amagma, cara therapeutics, daewoong, incyte corporation, om pharma, and pfizer; has served on advisory boards for astrazeneca, boehringer ingelheim, cara therapeutics, celgene corporation, regeneron pharmaceuticals, sanofi genzyme, and trevi therapeutics; is a shareholder in locus biosciences; and has a pending patent for jak inhibitors in chronic itch. sgk has served as an advisory board member or consultant for abbvie, galderma, incyte corporation, kiniksa pharmaceuticals, regeneron pharmaceuticals, and pfizer inc; and has received grant funding from pfizer inc, galderma, and kiniksa pharmaceuticals. mek was an employee and shareholder of incyte corporation at the time of development of the original presentation. mev and ks are employees and shareholders of incyte corporation. lk has served as an investigator, consultant, or speaker for abbvie, amgen, anaptys, arcutis, dermavant, eli lilly, glenmark, incyte corporation, kamedis, leo pharma, l’oreal, menlo therapeutics, novartis, ortho dermatologics, pfizer, regeneron, sanofi, sun pharma, and taro. acknowledgments the authors thank the patients, investigators, and investigational sites whose participation made the study possible. support for this study was provided by incyte corporation (wilmington, de, usa). the authors thank shaoceng wei, phd, of incyte corporation for providing statistical analysis support. writing assistance was provided by vicky kanta, phd, an employee of icon (north wales, pa, usa), and was funded by incyte corporation. references 1. langan sm, et al. lancet. 2020;396(10247):345-360. 2. silverberg ji, et al. ann allergy asthma immunol. 2018;121(3):340-347. 3. chrostowska-plak d, et al. acta derm venereol. 2009;89(4):379-383. 4. wei w, et al. j dermatol. 2018;45(2):150-157. 5. bao l, et al. jakstat. 2013;2(3):e24137. 6. oetjen lk, et al. cell. 2017;171(1):217-228. 7. papp k, et al. j am acad dermatol. 2021;85(4):863-872. 8. charman cr, et al. arch dermatol. 2004;140(12):1513-1519. 1oregon medical research center, portland, or, usa; 2wroclaw medical university, wroclaw, poland; 3k. papp clinical research and probity medical research, waterloo, on, canada; 4oregon health & science university, portland, or, usa; 5george washington university, washington, dc, usa; 6washington university school of medicine, st. louis, mo, usa; 7johns hopkins university school of medicine, baltimore, md, usa; 8incyte corporation, wilmington, de, usa; 9icahn school of medicine at mount sinai, new york, ny, usa itch-free state in patients with atopic dermatitis treated with ruxolitinib cream presented at the fall clinical dermatology conference las vegas, nv • october 21–24, 2021 to download a copy of this poster, scan code. deucravacitinib, an oral, selective tyrosine kinase 2 inhibitor, in moderate to severe plaque psoriasis: 52-week efficacy by prior treatment in the phase 3 poetyk pso-1 trial jerry bagel,1 april w armstrong,2 richard b warren,3 kim a papp,4 diamant thaçi,5 alan menter,6 jennifer cather,7 matthias augustin,8 lauren hippeli,9 carolin daamen,9 christopher e m griffiths3 1psoriasis treatment center of new jersey, east windsor, nj, usa; 2university of southern california, los angeles, ca, usa; 3dermatology centre, salford royal nhs foundation trust, nihr manchester biomedical research centre, the university of manchester, manchester, uk; 4k papp clinical research and probity medical research, waterloo, on, canada; 5institute and comprehensive center for inflammation medicine, university of lübeck, lübeck, germany; 6baylor university medical center, dallas, tx, usa; 7mindful dermatology and modern research associates, dallas, tx, usa; 8institute for health services research in dermatology and nursing, university medical center hamburg-eppendorf, hamburg, germany; 9bristol myers squibb, princeton, nj, usa presented at the 2022 fall clinical dermatology conference; october 20—23, 2022; las vegas, nv this is an encore of the 2022 31st eadv congress poster this poster may not be reproduced without written permission from the authors.email for jerry bagel, md: dreamacres1@icloud.com scientific content on demand to request a copy of this poster: scan qr code via a barcode reader application qr codes are valid for 30 days after congress presentation date synopsis • deucravacitinib an oral, selective, allosteric tyrosine kinase 2 (tyk2) inhibitor, is approved by the us food and drug administration for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy1 — uniquely binds to the regulatory domain rather than to the catalytic domain where janus kinase 1/2/3 inhibitors bind2,3 (figure 1) • in the global, 52-week, phase 3 poetyk pso-1 trial (nct03624127), deucravacitinib was significantly more effective than placebo or apremilast in the treatment of moderate to severe plaque psoriasis4 — clinical responses were maintained through 52 weeks5 • response rates for the coprimary endpoints, ≥75% reduction from baseline in psoriasis area and severity index (pasi 75) and static physician’s global assessment score of 0 (clear) or 1 (almost clear) with a ≥2-point improvement from baseline (spga 0/1) at week 16, were superior with deucravacitinib regardless of prior exposure to biologics, systemic nonbiologics, and/or phototherapy6 • the 2-year efficacy and safety of deucravacitinib in the poetyk long-term extension trial was consistent with weeks 0–52 of the poetyk pso-1 and pso-2 trials7 objective • the aim of the current analysis was to evaluate the impact of prior treatment on pasi 75 and spga 0/1 responses through week 52 in patients from poetyk pso-1 who were randomized to deucravacitinib and in those who crossed over from placebo to deucravacitinib at week 16 methods • the study design for poetyk pso-1 is illustrated in figure 2 • eligible patients were ≥18 years of age with moderate to severe plaque psoriasis (ie, pasi ≥12, spga ≥3, body surface area involvement ≥10% at baseline) • patients who previously received phototherapy, systemic treatment, and/or biologic treatment were required to complete washout periods ranging from 4 weeks to 6 months before study entry, depending on the treatment • the current analysis examined pasi 75 and spga 0/1 responses through 52 weeks in patients randomized to deucravacitinib and in those who crossed over from placebo to deucravacitinib at week 16 (placebo crossovers), by prior treatment subgroups: — systemic treatment naive (ie, neither biologic nor nonbiologic systemic treatment) — prior systemic treatment (biologic and/or nonbiologic) — prior oral systemic treatment (nonbiologic only) — biologic treatment naive — biologic treatment experienced • nonresponder imputation was used for all reported endpoints figure 2. poetyk pso-1 study design poetyk pso-1 (n = 666) deucravacitinib 6 mg qdplacebo (n = 166) deucravacitinib 6 mg qd<pasi 50 apremilast 30 mg bid titrate* 1 :2 :1 r an d o m iz at io n weeks 16 24 520 deucravacitinib 6 mg qd (n = 332) primary endpoint apremilast 30 mg bida (n = 168) ≥pasi 50 aapremilast was titrated from 10 mg qd to 30 mg bid over the first 5 days of dosing. bid, twice daily; pasi 50, ≥50% reduction from baseline in psoriasis area and severity index; qd, once daily. results • baseline demographics and disease characteristics for patients randomized to deucravacitinib (n = 332) and to placebo (n = 166) are shown in table 1 — prior use of systemic (biologic and nonbiologic), oral systemic, and biologic treatments was generally similar between the groups (table 1) • at week 52, pasi 75 response rates were similar in patients randomized to deucravacitinib at baseline and in placebo crossovers (65.1% and 68.3%, respectively) (table 2; figure 3) • these findings were consistent across all patient subgroups (table 2), including: — systemic treatment-naive patients and those with prior systemic or oral systemic treatment (figure 4) — patients with and without prior biologic treatment (figure 5) • at week 52, spga 0/1 response rates were similar in patients randomized to deucravacitinib at baseline and in placebo crossovers (53.8% and 52.7%, respectively) (figure 6) • these findings were consistent across all patient subgroups (table 2), including: — systemic treatment-naive patients and those with prior systemic or oral systemic treatment (figure 7) — patients with and without prior biologic treatment (figure 8) table 1. baseline patient demographics and disease characteristics parameter poetyk pso-1 placebo (n = 166) deucravacitinib (n = 332) age, mean (min, max), y 47.9 (19, 81) 45.9 (18, 80) weight, mean (min, max), kg 89.1 (46.3, 181.6) 87.9 (36.0, 173.0) female, n (%) 53 (31.9) 102 (30.7) race, n (%) white 128 (77.1) 267 (80.4) asian 34 (20.5) 59 (17.8) other 4 (2.4) 6 (1.8) disease duration, mean (min, max), y 17.3 (0.9, 62.3) 17.1 (0.7, 57.8) spga, n (%) 3 (moderate) 128 (77.1) 257 (77.4) 4 (severe) 37 (22.3) 75 (22.6) pasi, mean (min, max) 20.7 (10.3, 47.7) 21.8 (12.0, 58.8) pssd symptom score, mean (min, max) 51.4 (0.3, 100.0) 51.7 (0.0, 100.0) dlqi, mean (min, max) 11.4 (1.0, 30.0) 12.0 (0.0, 30.0) prior treatment use, n (%) systemic treatment naive 57 (34.3) 132 (39.8) prior systemic treatment 109 (65.7) 200 (60.2) prior oral systemic treatment 73 (44.0) 114 (34.3) biologic treatment naive 103 (62.0) 202 (60.8) prior biologic treatment 63 (38.0) 130 (39.2) dlqi, dermatology life quality index; pasi, psoriasis area and severity index; pssd, psoriasis symptoms and signs diary; spga, static physician’s global assessment. table 2. summary of week 52 response rates (nri)a patients poetyk pso-1 pasi 75 week 52 response rate, n/n (%) spga 0/1 week 52 response rate, n/n (%) placebo – deucravacitinib deucravacitinib placebo – deucravacitinib deucravacitinib full analysis set 99/145 (68.3) 216/332 (65.1) 78/145 (53.8) 175/332 (52.7) systemic treatment naive 35/51 (68.6) 85/132 (64.4) 26/51 (51.0) 69/132 (52.3) prior systemic treatment 64/94 (68.1) 131/200 (65.5) 52/94 (55.3) 106/200 (53.0) prior oral systemic treatment 45/65 (69.2) 80/114 (70.2) 35/65 (53.8) 65/114 (57.0) biologic treatment naive 65/90 (72.2) 136/202 (67.3) 53/90 (58.9) 113/202 (55.9) prior biologic treatment 34/55 (61.8) 80/130 (61.5) 25/55 (45.5) 62/130 (47.7) apatients who missed efficacy assessments due to covid-19 were excluded from efficacy analyses at those time points. nri, nonresponder imputation; pasi 75, ≥75% reduction from baseline in psoriasis area and severity index; spga 0/1, static physician’s global assessment score of 0 (clear) or 1 (almost clear) with a ≥2-point improvement from baseline. figure 3. pasi 75 response rates through week 52, full analysis set (nri)a 58.4% 65.1% 12.7% 68.3% 0 10 20 30 40 50 60 p a si 7 5 re sp on se r at e, % o f pa ti en ts 70 80 90 100 0 1 2 4 8 12 16 primary endpoint 20 weeks 24 28 32 36 40 44 48 52 332 332 332 332 332 332 332 332 332 332 330 326 320 324 325 332 166 deucravacitinib patients, n placebo – deucravacitinib 166 166 166 166 166 166 145 145 144 144 145 142 144 145 145 deucravacitinib placebo → deucravacitinib apatients who missed efficacy assessments due to covid-19 were excluded from efficacy analyses at those time points. nri, nonresponder imputation, pasi 75, ≥75% reduction from baseline in psoriasis area and severity index. figure 4. pasi 75 response rates through week 52 in systemic treatment-naive, prior systemic treatment, and prior oral systemic treatment patients (nri)a deucravacitinib placebo → deucravacitinib patients, n 0 10 20 30 40 50 60 p a si 7 5 re sp on se r at e, % o f pa ti en ts 70 80 90 100 0 1 2 4 8 12 16 primary endpoint 20 weeks systemic treatment naive 24 28 32 36 40 44 48 52 132 132 132 132 132 132 132 132 132 132 132 127 122 127 129 132 57 deucravacitinib placebo – deucravacitinib 57 57 57 57 57 57 51 51 51 51 51 50 51 51 51 56.8% 64.4% 21.1% 68.6% patients, n 0 10 20 30 40 50 60 p a si 7 5 re sp on se r at e, % o f pa ti en ts 70 80 90 100 0 1 2 4 8 12 16 primary endpoint 20 weeks prior systemic treatment 24 28 32 36 40 44 48 52 200 200 200 200 200 200 200 200 200 200 198 199 198 197 196 200 109 deucravacitinib placebo – deucravacitinib 109 109 109 109 109 109 94 94 93 93 94 92 93 94 94 59.5% 65.5% 8.3% 68.1% patients, n 0 10 20 30 40 50 60 p a si 7 5 re sp on se r at e, % o f pa ti en ts 70 80 90 100 0 1 2 4 8 12 16 primary endpoint 20 weeks prior oral systemic treatment 24 28 32 36 40 44 48 52 114 114 114 114 114 114 114 114 114 114 113 113 113 112 111 114 73 deucravacitinib placebo – deucravacitinib 73 73 73 73 73 73 65 65 65 65 65 65 65 65 65 58.8% 70.2% 9.6% 69.2% apatients who missed efficacy assessments due to covid-19 were excluded from efficacy analyses at those time points. nri, nonresponder imputation; pasi 75, ≥75% reduction from baseline in psoriasis area and severity index. figure 5. pasi 75 response rates through week 52 in biologic treatment-naive and prior biologic treatment patients (nri)a deucravacitinib placebo → deucravacitinib patients, n 0 10 20 30 40 50 60 p a si 7 5 re sp on se r at e, % o f pa ti en ts 70 80 90 100 0 1 2 4 8 12 16 primary endpoint 20 weeks biologic treatment naive 24 28 32 36 40 44 48 52 202 202 202 202 202 202 202 202 202 202 202 197 192 195 196 202 103 deucravacitinib placebo – deucravacitinib 103 103 103 103 103 103 90 90 90 90 90 89 90 90 90 patients, n 0 10 20 30 40 50 60 p a si 7 5 re sp on se r at e, % o f pa ti en ts 70 80 90 100 0 1 2 4 8 12 16 primary endpoint 20 weeks prior biologic treatment 24 28 32 36 40 44 48 52 130 130 130 130 130 130 130 130 130 130 128 129 128 129 129 130 63 deucravacitinib placebo – deucravacitinib 63 63 63 63 63 63 55 55 54 54 55 53 54 55 55 59.9% 67.3% 15.5% 72.2% 56.2% 61.5% 7.9% 61.8% apatients who missed efficacy assessments due to covid-19 were excluded from efficacy analyses at those time points. nri, nonresponder imputation; pasi 75, ≥75% reduction from baseline in psoriasis area and severity index. figure 6. spga 0/1 response rates through week 52, full analysis set (nri)a 0 10 20 30 40 50 60 sp g a 0 /1 r es po n se r at e, % o f pa ti en ts 70 80 90 100 0 1 2 4 8 12 16 primary endpoint 20 weeks 24 28 32 36 40 44 48 52 332 332 332 332 332 332 332 332 332 332 330 326 320 324 325 332 166 deucravacitinib patients, n placebo – deucravacitinib 166 166 166 166 166 166 145 145 144 144 145 142 144 145 145 deucravacitinib placebo → deucravacitinib 53.6% 52.7% 7.2% 53.8% apatients who missed efficacy assessments due to covid-19 were excluded from efficacy analyses at those time points. nri, nonresponder imputation; spga 0/1, static physician’s global assessment score of 0 (clear) or 1 (almost clear) with a ≥2-point improvement from baseline. figure 7. spga 0/1 response rates through week 52 in systemic treatment-naive, prior systemic treatment, and prior oral systemic treatment patients (nri)a deucravacitinib placebo → deucravacitinib patients, n 0 10 20 30 40 50 60 sp g a 0 /1 r es po n se r at e, % o f pa ti en ts 70 80 90 100 0 1 2 4 8 12 16 primary endpoint 20 weeks systemic treatment naive 24 28 32 36 40 44 48 52 132 132 132 132 132 132 132 132 132 132 132 127 122 127 129 132 57 deucravacitinib placebo – deucravacitinib 57 57 57 57 57 57 51 51 51 51 51 50 51 51 51 patients, n 0 10 20 30 40 50 60 sp g a 0 /1 r es po n se r at e, % o f pa ti en ts 70 80 90 100 0 1 2 4 8 12 16 primary endpoint 20 weeks prior systemic treatment 24 28 32 36 40 44 48 52 200 200 200 200 200 200 200 200 200 200 198 199 198 197 196 200 109 deucravacitinib placebo – deucravacitinib 109 109 109 109 109 109 94 94 93 93 94 92 93 94 94 patients, n 0 10 20 30 40 50 60 sp g a 0 /1 r es po n se r at e, % o f pa ti en ts 70 80 90 100 0 1 2 4 8 12 16 primary endpoint 20 weeks prior oral systemic treatment 24 28 32 36 40 44 48 52 114 114 114 114 114 114 114 114 114 114 113 113 113 112 111 114 73 deucravacitinib placebo – deucravacitinib 73 73 73 73 73 73 65 65 65 65 65 65 65 65 65 53.0% 52.3% 5.3% 51.0% 54.0% 53.0% 8.3% 55.3% 50.9% 57.0% 9.6% 53.8% apatients who missed efficacy assessments due to covid-19 were excluded from efficacy analyses at those time points. nri, nonresponder imputation; spga 0/1, static physician’s global assessment score of 0 (clear) or 1 (almost clear) with a ≥2-point improvement from baseline. figure 8. spga 0/1 response rates through week 52 in biologic treatment-naive and prior biologic treatment patients (nri)a 50.0% 45.5% 6.3% 47.7% 0 10 20 30 40 50 60 sp g a 0 /1 r es po n se r at e, % o f pa ti en ts 70 80 90 100 0 1 2 4 8 12 16 primary endpoint 20 weeks 24 28 32 36 40 44 48 52 130 130 130 130 130 130 130 130 130 130 128 129 128 129 129 130 63placebo – deucravacitinib 63 63 63 63 63 63 55 55 54 54 55 53 54 55 55 deucravacitinib placebo → deucravacitinib 55.9% 55.9% 58.9% 0 10 20 30 40 50 60 sp g a 0 /1 r es po n se r at e, % o f pa ti en ts 70 80 90 100 0 1 2 4 8 12 16 primary endpoint 20 weeks biologic treatment naive prior biologic treatment 24 28 32 36 40 44 48 52 202 202 202 202 202 202 202 202 202 202 202 197 192 195 196 202 103placebo – deucravacitinib 103 103 103 103 103 103 90 90 90 90 90 89 90 90 90 patients, n deucravacitinib patients, n deucravacitinib 7.8% apatients who missed efficacy assessments due to covid-19 were excluded from efficacy analyses at those time points. nri, nonresponder imputation; spga 0/1, static physician’s global assessment score of 0 (clear) or 1 (almost clear) with a ≥2-point improvement from baseline. figure 1. mechanism of action of deucravacitinib tyk2 deucravacitinib (allosteric inhibitor) unique regulatory domain catalytic domain (highly conserved across jak family) atp-binding active site (other kinase inhibitors) •  ≥100-fold greater selectivity for tyk2 vs jak 1/3 • ≥2000-fold greater selectivity for tyk2 vs jak 2 selectivity in cells2,3: atp, adenosine 5′-triphosphate; jak, janus kinase; tyk2, tyrosine kinase 2. disclosures • jb: research funds payable to the psoriasis treatment center of new jersey: abbvie, amgen, arcutis, boehringer ingelheim, bristol myers squibb, celgene, corevitas' (corrona) psoriasis registry, dermavant, dermira/ucb, eli lilly, glenmark, janssen biotech, kadmon, leo pharma, lycera, menlo therapeutics, novartis, pfizer, regeneron, sun pharma, taro, and valeant; consultant: abbvie, amgen, celgene, eli lilly, janssen biotech, novartis, sun pharma, and valeant; speaker: abbvie, celgene, eli lilly, janssen biotech, and novartis • awa: grants and personal fees: abbvie, bristol myers squibb, eli lilly, janssen, leo pharma, and novartis; personal fees: boehringer ingelheim/parexel, celgene, dermavant, genentech, glaxosmithkline, menlo therapeutics, merck, modernizing medicine, ortho dermatologics, pfizer, regeneron, sanofi genzyme, science 37, sun pharma, and valeant; grants: dermira, kyowa hakko kirin, and ucb, outside the submitted work • rbw: research grants: abbvie, almirall, amgen, celgene, eli lilly, janssen, leo pharma, novartis, pfizer, and ucb; consulting fees: abbvie, almirall, amgen, biogen, boehringer ingelheim, celgene, dice, eli lilly, janssen, leo pharma, novartis, pfizer, sanofi, ucb, and union • kap: consultant: abbvie, acelyrin, akros, amgen, aralez pharmaceuticals, arcutis, avillion, bausch health/valeant, boehringer ingelheim, bristol myers squibb, can-fite biopharma, celgene, celltrion, coherus, dermavant, dermira, dice therapeutics, dow pharma, eli lilly, evelo, forbion, galderma, incyte, janssen, kyowa hakko kirin, leo pharma, meiji seika pharma, merck (msd), mitsubishi pharma, novartis, pfizer, regeneron, reistone, roche, sanofi aventis/genzyme, sandoz, sun pharma, takeda, ucb, vtv therapeutics, and xencor; speakers bureau: abbvie, amgen, bausch health/valeant, celgene, eli lilly, galderma, incyte, janssen, kyowa hakko kirin, leo, merck (msd), novartis, pfizer, and sanofi aventis/genzyme; clinical research grants: abbvie, akros, amgen, anacor, arcutis, avillion, bausch health/valeant, boehringer ingelheim, bristol myers squibb, can-fite biopharma, celgene, coherus, dermavant, dermira, dice therapeutics, dow pharma, eli lilly, evelo, galderma, gilead, gsk, incyte, janssen, kyowa hakko kirin, leo pharma, merck (msd), novartis, pfizer, regeneron, roche, sanofi aventis/genzyme, sun pharma, takeda, and ucb; honoraria: abbvie, acelyrin, akros, amgen, aralez pharmaceuticals, bausch health/valeant, boehringer ingelheim, celgene, celltrion, coherus, dermavant, dice therapeutics, eli lilly, forbion, galderma, janssen, kyowa hakko kirin, leo pharma, meiji seika pharma, merck (msd), mitsubishi pharma, novartis, pfizer, reistone, sanofi aventis/genzyme, sandoz, sun pharma, takeda, ucb, vtv therapeutics, and xencor; scientific officer: akros, anacor, arcutis, dice therapeutics, and kyowa hakko kirin; steering committees: abbvie, amgen, bausch health/valeant, boehringer ingelheim, celgene, eli lilly, janssen, kyowa hakko kirin, merck (msd), novartis, pfizer, regeneron, reistone, and sanofi aventis/genzyme; advisory boards: abbvie, amgen, bausch health/valeant, boehringer ingelheim, bristol myers squibb, celgene, dice therapeutics, dow pharma, eli lilly, galderma, janssen, merck (msd), novartis, pfizer, regeneron, sanofi aventis/genzyme, sun pharma, and ucb • dt: grant/research support, consultant, scientific advisory board, and speakers bureau: abbvie, almirall, amgen, biogen idec, boehringer ingelheim, bristol myers squibb, eli lilly, galapagos, galderma, janssen-cilag, leo pharma, novartis, pfizer, regeneron, roche, sandoz-hexal, sanofi, target-solution, and ucb • am: advisory boards: abbvie, amgen, boehringer ingelheim, janssen biotech, and leo pharma; consulting fees: abbvie, amgen, eli lilly, janssen biotech, leo pharma, novartis, sun pharma, and ucb; honoraria: abbvie, amgen, boehringer ingelheim, eli lilly, janssen biotech, leo pharma, novartis, sun pharma, and ucb; investigator: abbvie, amgen, boehringer ingelheim, celgene, eli lilly, janssen biotech, leo pharma, merck, novartis, sun pharma, and ucb; research grants: abbvie, amgen, boehringer ingelheim, celgene, janssen biotech, leo pharma, merck, and sun pharma; speaker: abbvie, amgen, janssen biotech, leo pharma, sun pharma, and ucb • jc: clinical trials: eli lilly, sun pharma, chemocentryx, janssen, ucb, amgen, abbvie, galderma, bristol myers squibb; consulting fees: amgen, abbvie, eli lilly, sanofi genzyme, bristol myers squibb, dermavant. speakers bureau: amgen, abbvie, and eli lilly • ma: advisory boards: abbvie, amgen, boehringer ingelheim, janssen biotech, and leo pharma; consulting fees: abbvie, amgen, eli lilly, janssen biotech, leo pharma, novartis, sun pharma, and ucb; honoraria: abbvie, amgen, boehringer ingelheim, eli lilly, janssen biotech, leo pharma, novartis, sun pharma, and ucb; investigator: abbvie, amgen, boehringer ingelheim, celgene, eli lilly, janssen biotech, leo pharma, merck, novartis, sun pharma, and ucb; research grants: abbvie, amgen, boehringer ingelheim, celgene, janssen biotech, leo pharma, merck, and sun pharma; speaker: abbvie, amgen, janssen biotech, leo pharma, sun pharma, and ucb • lh and cd: employees and shareholders: bristol myers squibb • cemg: honoraria and/or research grants from abbvie, almirall, amgen, anaptysbio, bristol myers squibb, eli lilly, glaxosmithkline, janssen, leo pharma, novartis, sanofi, and ucb conclusions • deucravacitinib-treated patients from the poetyk pso-1 trial maintained response rates for pasi 75 and spga 0/1 through week 52, regardless of prior treatment exposure to biologic, systemic nonbiologic, and/or oral systemic agents • patients who switched from placebo to deucravacitinib at week 16 also showed robust responses at week 52 on both endpoints and across subgroups • these analyses support the efficacy of deucravacitinib in moderate to severe psoriasis regardless of prior treatment history references 1. sotyktu™ (deucravacitinib) [package insert]. princeton, nj: bristol-myers squibb company; september 2022. 2. burke jr, et al. sci transl med. 2019;11:eaaw1736. 3. wrobleski st, et al. j med chem. 2019;62:8973-8995. 4. armstrong aw, et al. j am acad dermatol. 2022;s0190-9622(22)02256-3. doi: 10.1016/j.jaad.2022.07.002. online ahead of print. 5. warren rb, et al. presented at the european academy of dermatology and venereology (eadv) 30th congress, september 29–october 2, 2021. late breaker. 6. warren rb, et al. presented at the european academy of dermatology and venereology (eadv) 30th congress, september 29–october 2, 2021. 7. warren rb, et al. presented at the eadv spring symposium; may 12–14, 2022. acknowledgments • this study was sponsored by bristol myers squibb • writing and editorial assistance was provided by liz rockstein, phd, of peloton advantage, llc, an open health company, parsippany, nj, usa, funded by bristol myers squibb skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 445 skimages the biett collarette as an important dermoscopic finding of secondary syphilis malvika ramesh1, jeremy purser md2, michelle tarbox md2 1 texas tech university health sciences center, school of medicine, lubbock, tx 2 texas tech university health sciences center, department of dermatology, lubbock, tx syphilis is a sexually transmitted disease caused by the bacteria treponema pallidum. the disease progresses through stages with different symptoms and organ systems affected at each stage. primary syphilis is characterized by a painless chancre that appears on the genitals,1 while secondary syphilis occurs about 6-8 weeks later and historically affects the skin. secondary syphilis is characterized by various cutaneous manifestations and can be difficult to diagnose due to the variability of presentations and similarity to other figure 2. erythematous papular rash: composed of 5-8mm erythematous papules present on the patient's trunk and lower extremities. figure 1. dermoscopic finding of biett collarette: peripheral scaling around individual lesions consistent with early syphilis skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 446 dermatologic conditions.1 macules, papules, and pustules can occur together and are often accompanied by generalized lymphadenopathy and nonspecific symptoms such as fever, chills, fatigue. early recognition of symptoms and initiation of treatment are critical for preventing progression. the variety of cutaneous presentations seen in secondary syphilis can mimic other dermatologic pathologies and make diagnosis difficult. however, the individual lesions seen in secondary syphilis can be distinguished by a peripheral scale called biett’s collarette [figure 1] and dermoscopy can aid physicians in clueing into the right diagnosis via visualization of this unique finding. this can greatly improve the diagnosis of syphilis when nonspecific lesions are seen early in the disease course, and we encourage providers to use dermoscopy to aid in the diagnosis when presented with a vague maculopapular rash and suspicion for syphilis. here we present a 44-year-old female who presented to an outpatient clinic with a rash [figure 2] that began 1 month prior. the rash arose on her lower legs and ankles and spread to her chest, groin, and face. she denied any change in the size or nature of the lesions. the rash was pruritic. on exam, the rash was composed of 4-8 mm erythematous papules with a collarette of scale appearing throughout the lower extremities to trunk palmoplantar involvement was noted. punch biopsy of the rash and serologic work up for syphilis were done. dermoscopic findings of her rash showed peripheral scaling around individual lesions consistent with a biett collarette (figures 1 and 2), thus cluing into the underlying diagnosis of syphilis.2,3 biett collarette can be seen as peripheral scaling in early syphilis surrounding light pink or erythematous macules and later in syphilis surrounding erythematous papules.4 biopsy as well as reactive plasma reagin (rpr) and fluorescent treponemal antibody absorption (fta-abs) testing confirmed the diagnosis. the patient was instructed to follow up with the health department regarding further syphilis treatment and serologic monitoring. as seen in this case, dermoscopy can assist the clinician in recognizing biett’s sign when presented with a vague annular maculopapular rash.5 3 this article aims to aid and encourage dermoscopic evaluation of rashes suspect of secondary syphilis to help in the diagnosis of a historically difficult to diagnosis condition. conflict of interest disclosures: none funding: none corresponding author: malvika ramesh texas tech school of medicine 3601 4th st lubbock, tx 79430 email: malvika.ramesh@hotmail.com references: 1. balagula y, mattei pl, wisco oj, erdag g, chien al. the great imitator revisited: the spectrum of atypical cutaneous manifestations of secondary syphilis. int j dermatol. 2014;53(12):1434-1441. doi:10.1111/ijd.12518 2. reinehr cph, kalil clpv, reinehr vph. secondary syphilis: the great imitator can't be forgotten. rev assoc med bras (1992). 2017;63(6):481-483. doi:10.1590/18069282.63.06.481 3. tognetti l, sbano p, fimiani m, rubegni p. dermoscopy of biett's sign and differential diagnosis with annular maculo-papular rashes with scaling. indian j dermatol venereol leprol. 2017;83(2):270-273. doi:10.4103/03786323.196318 4. esther xavier de brito m, antonio pedro, antonio sergio et al. secondary syphilis with exuberant manifestations. journal of american academy of dermatology association. 2013;68(4). doi: https://doi.org/10.1016/j.jaad.2012.12.512 https://doi.org/10.1016/j.jaad.2012.12.512 skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 447 5. kasuya a, aoshima m, fukuchi k, shimauchi t, fujiyama t, tokura y. an intuitive explanation of dermoscopic structures by digitally reconstructed pathological horizontal top-down view images. sci rep. 2019;9(1):19875. published 2019 dec 27. doi:10.1038/s41598-019-56522-8 skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 256 brief articles safe use of interleukin-17 inhibitors for psoriasis and psoriatic arthritis in two patients with a history of lymphoproliferative disease stephen sansone1, yasmin amir, md1, mark g. lebwohl, md1 1department of dermatology, icahn school of medicine at mount sinai, new york, ny psoriasis and psoriatic arthritis are chronic, inflammatory, immune-mediated diseases that affect the skin and joints, respectively. in recent years, systemic agents such as methotrexate, cyclosporine, and the tumor necrosis factor-α (tnf-α) inhibitors, have significantly improved our ability to treat psoriasis and psoriatic arthritis. however, these medications are associated with side effects and concerns for long-term risks, specifically that of an increased risk of malignancies like lymphoma.1-4 recent discovery of key components in the pathogenesis of psoriasis has led to the development of novel therapies targeting interleukins (ils) 12, 23, and 17. data from clinical trials for these agents reveals favorable, minimal side effect profiles.5-8 as these newer medications have only been available for limited time, further studies are needed to determine their long-term safety. here we report two cases of patients with psoriasis and psoriatic arthritis who had histories of lymphoma, both successfully treated with an interleukin-17 inhibitor without any recurrence of lymphoproliferative disease. patient 1 a 78-year-old woman with hypertension, chronic obstructive pulmonary disease, psoriasis, psoriatic arthritis, and mycosis fungoides presented to our clinic in 2002. she was diagnosed with mycosis fungoides at that time and the disease has been well introduction case presentation psoriasis and psoriatic arthritis are chronic, inflammatory, immune-mediated diseases that affect the skin and joints, respectively. the older systemic agents that have been used to treat these conditions are associated with many side effects, including an increased risk of malignancies, specifically lymphoma. in the last few years, there has been a wave of development of novel systemic biologic therapies to target psoriasis and psoriatic arthritis. while long-term safety data is lacking, the newer therapies targeting interleukins 12, 23, and 17 reveal a much more favorable side effect profile, specifically with regards to lymphoma. here we report two cases of patients with psoriasis and psoriatic arthritis who had histories of lymphoma, both successfully treated with an interleukin-17 inhibitor without any recurrence or worsening of lymphoproliferative disease. abstract skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 257 controlled on puva in the years since. in 2017, her psoriatic joint pain became severe and debilitating. in light of this, the decision was made to begin systemic medication. she was not a candidate for treatment with tnfα inhibitors due to her diagnosis of mycosis fungoides. in conjunction with her hematologist-oncologist, secukinumab was initiated at doses of 300mg weekly for the first five weeks, then once every four weeks thereafter. the patient is now five months into her treatment with secukinumab. at this time, she has had great improvement in her arthritis symptoms and remains free of new or worsening mycosis fungoides. patient 2 a 68-year-old woman with hypothyroidism and psoriasis presented to our clinic in 2016. she had psoriasis involving her trunk, buttocks, elbows, ankles, and scalp for over 20 years. she had failed treatment with topical steroids, intralesional steroids, apremilast, and etanercept. in 2004 she was diagnosed with stage i follicular lymphoma, which was successfully treated with lymph node dissection. at the time of presentation in 2016, she had moderate to severe disease, and the decision was made to begin systemic medication. she was not a candidate for treatment with tnf-α inhibitors due to her history of lymphoma. after discussion with her hematologist-oncologist, secukinumab was initiated at doses of 300mg weekly for the first five weeks, then once every four weeks thereafter. the patient initially experienced a greater than 50% improvement in her psoriatic lesions. however, after nine months of therapy with secukinumab, she began to flare. at this point she was switched to brodalumab 210mg at week 0, week 1, week 2, and then every two weeks thereafter. the patient is now twelve months into her treatment with brodalumab. at this time, her skin is clear of psoriasis and she remains without any evidence of recurrence of lymphoma. with a broad armamentarium of available treatment options for psoriasis and psoriatic arthritis, it becomes important to separate treatments based on safety profile in specific patient populations. here, we report two cases in which patients with a known history of lymphoproliferative disease were safely treated with an il-17 inhibitor. while further studies regarding long-term safety profile are necessary, our cases highlight that the il-17 inhibitors may be both safe and effective in patients with a history of lymphoproliferative disease. psoriasis itself has been associated with an increased risk of lymphoproliferative disorders. this has been evidenced by multiple studies, including a cohort study by gelfand et al. which compared adults over 65 with psoriasis to adults over 65 without psoriasis and found a three-fold increased risk of lymphoma.9 as psoriasis itself is associated with an increased risk of malignancy, the interpretation of data regarding the additional risk posed by systemic therapies is challenging. the biologic small molecules, methotrexate and cyclosporine, have both been associated with an increased risk of malignancy, specifically lymphoproliferative disease, in literature pertaining to both rheumatoid arthritis and psoriasis patients.4 importantly, however, the psoriasis longitudinal assessment and registry (psolar) did not find an increased risk of malignancy, with the exclusion of non-melanoma skin cancer, in patients receiving methotrexate for psoriasis.10 discussion skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 258 the tnf-α inhibitors, infliximab, adalimumab, and etanercept, have all been reported to be associated with hematologic malignancy. the food and drug administration (fda) package inserts for all three medications include a black box warning for the risk of malignancy, in particular highlighting lymphoma.1-3 there have been numerous case reports, case series, and meta-analyses of pooled data that have suggested an increased risk of lymphoproliferative disease with the tnf-α inhibitors, both alone and in combination with other immunosuppressive agents. in psolar data, long-term use, defined as greater than twelve months, was found to be associated with malignancy, excluding nonmelanoma skin cancer.10 while the long-term safety data for the il-17 inhibitors is lacking at this time, there is some preliminary supporting evidence for their safety with regards to malignancy. thus far, malignancy incidence rates in patients on these biologic agents have been shown to be less than or comparable to those for the general population.11 from a molecular standpoint, multiple experiments have shown that il-17 plays an essential role in the pathophysiology of cancer, potentially stimulating the formation of tumors via increased expression of antiapoptotic genes and therefore increased tumor cell survival.12 additionally, studies in mouse models have found that just as increases in il-17 have been noted in tumor states, knocking out il-17 has led to decreased tumor growth.12 it may therefore be extrapolated that blocking the expression of il-17 with biologic drugs would not only be safe in patients with malignancy, but that targeting these interleukins may one day actually play a role in decreasing tumor occurrence. in summary, while there remains a need to further characterize the long-term safety of the new il-17 inhibitors for the treatment of psoriasis and psoriatic arthritis, there is some preliminary evidence suggesting that these medications may be safe in patients with a history of lymphoproliferative disorders. here, we describe two cases in which patients with a known history of lymphoproliferative disease were safely treated with il-17 inhibitors, without evidence of recurrence of their malignancy to date. conflict of interest disclosures: stephen sansone has no relevant conflicts of interest to declare. yasmin amir, md has no relevant conflicts of interest to declare. mark lebwohl, md is an employee of mount sinai and receives research funds from: abbvie, amgen, arcutis, astrazeneca, boehringer ingelheim, celgene, clinuvel, corrona, inc., eli lilly, foundation for research & education of dermatology, incyte, janssen research & development, llc, kadmon corp., llc, leo pharmaceutucals, medimmune, novartis, ortho dermatologics, pfizer, sciderm, ucb, inc., and vidac. dr. lebwohl is also a consultant for allergan, almirall, arcutis, inc., boehringer-ingelheim, bristolmyers squibb, leo pharma, menlo, mitsubishi, neuroderm, promius/dr. reddy’s laboratories, theravance, and verrica. funding: none corresponding author: yasmin amir, md department of dermatology icahn school of medicine at mount sinai 1425 madison ave, 2nd floor, new york, ny 10029 phone: 212-241-9728 email: yasmin.amir@mountsinai.org references: 1. remicade (infliximab) [package insert]. horsham, pa; janssen biotech, inc;. 1998. 2. enbrel (etanercept) [package insert]. thousand oaks, ca; amgen;. 1998. 3. humira (adalimumab) [package insert]. north chicago, abbvie lab. 2002. 4. patel rv, clark ln, lebwohl m, weinberg jm. treatments for psoriasis and the risk of mailto:yasmin.amir@mountsinai.org skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 259 malignancy. j am acad dermatol. 2009 jun:60(6):1001-17. 5. leonardi cl, kimball ab, papp ka et al. effi cacy and safety of ustekinumab , a human interleukin-12 / 23 monoclonal antibody , in patients with psoriasis : 76-week results from a randomised , double-blind , placebo-controlled trial ( phoenix 1 ). lancet. 2008;371(9625):1665-1674. doi:10.1016/s01406736(08)60726-6. 6. langley rg, elewski be, lebwohl m, et al. secukinumab in plaque psoriasis--results of two phase 3 trials. n engl j med. 2014;371(4):326338. doi:10.1056/nejmoa1314258. 7. griffiths cem, reich k, lebwohl m, et al. comparison of ixekizumab with etanercept or placebo in moderate-to-severe psoriasis (uncover-2 and uncover-3): results from two phase 3 randomised trials. lancet. 2015;386(9993):541-551. doi:10.1016/s01406736(15)60125-8 8. lebwohl m, strober b, menter a, et al. phase 3 studies comparing brodalumab with ustekinumab in psoriasis. n engl j med. 2015;373(14):1318-1328. doi:10.1056/nejmoa1503824. 9. gelfand jm, berlin j, van voorhees a, margolis dj. lymphoma rates are low but increased in patients with psoriasis. arch dermatol, 139 (2003); 1425-1429. 10. fiorentino d, ho v, lebwohl mg, leite l, hopkins l, galindo c, et al. risk of malignancy with systemic psoriasis treatment in the psoriasis longitudinal assessment registry. j am acad dermatol. 2017;77(5):845-854. 11. geller s, xu h, lebwohl m, nardone b, lacouture me, kheterpal m. malignancy risk and recurrence with psoriasis and its treatments: a concise update. am j clin dermatol. 2018 jun:19(3):363-375 12. nam js, terabe m, kang mj, chae h, voong n, et al. transforming growth factor beta subverts the immune system into directly promoting tumor growth through interleukin-17. cancer res. 2008 may; 68(10). skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 616 brief article community educational interventions: an effective means to improve photoprotection and skin cancer awareness in outdoor occupational workers ana preda-naumescu, bs1, josiah w. sowell1, bs, sydney a. weir, msph1, siddharth srikakolapu, ba1, om u. patel, bs1, isabella aldana, bs1, natalie h. garcia, bs1, lauren c.s. kole, md2 1university of alabama at birmingham school of medicine, birmingham, al 2department of dermatology, university of alabama at birmingham school of medicine, birmingham, al skin cancer is a preventable, yet leading cause of cancer in the united states. populations with increased sun exposure, such as outdoor workers, are at an increased risk of skin cancer due to environmental conditions at work sites.1,2 research demonstrates that this population receives increased ultraviolet radiation (uvr) exposure than the general population yet has lower rates of sunscreen use.1,2 review of the literature on outdoor workers' sun related knowledge, attitudes, and protective behaviors found that photoprotective behaviors are not widely implemented or recognized among outdoor working professionals.1,2,3,4 safety education programs have the potential to improve abstract introduction: outdoor workers are at increased risk for developing skin cancer compared to the general population due to environmental conditions at work sites and riskier behavior regarding skin cancer risk factors. in many populations, sun protection education is associated with increased use of sun protective measures. this study aimed to assess outdoor workers’ knowledge of sun safety and evaluate the impact of educational measures on the awareness of photoprotection practices. methods: a group of medical students visited construction sites in birmingham, al, to deliver 20-minute presentations on the risks of prolonged uv exposure and the prevention of photodamage. identical 10-question surveys were given to each participant before and after the presentation. participants rated their level of agreement with statements on photoprotection and skin cancer. results: the survey response rate was 79%. analysis revealed an average pre-presentation score of 3.01 and a post-presentation score of 3.73, on a scale from 1 to 5. two-sample paired t-tests for each question yielded statistically significant results (p <0.05). conclusion: outdoor occupational workers reported a better understanding of the risks of uv exposure and a greater willingness to engage in sun-protective practices following a brief educational intervention. these findings suggest that community-based education may improve awareness regarding photoprotection and skin cancer risk. introduction skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 617 adherence to sun protection and minimize risky behavior in these individuals.5 a cross-sectional study was conducted to better understand the attitudes, perceptions, and behaviors of outdoor workers regarding photoprotection and occupational skin cancer risk. the university of alabama at birmingham (uab) institutional review board approved the research protocol to implement educational interventions at ten local construction sites in the birmingham area. presentation slides and a 10-item survey were generated through the collaboration of uab medical students and board-certified dermatologists. participants completed a 10-item survey prior to a 20minute interactive lecture, designed to educate participants about skin cancer risk factors and photoprotective strategies. an identical post survey was readministered immediately following the presentation. survey questions measured how likely participants were to engage in sun protective behaviors or how knowledgeable they were of skin cancer risk factors. answers were graded on a scale from 1 to 5, with 1 indicating “not at all” and 5 indicating “extremely.” among the 210 outdoor workers who attended the presentation, 166 sets of surveys (response rate 79%) were collected. jmp v. 16 was used for statistical analysis. a two-sample paired t-test was performed and yielded statistically significant results (p<0.05) across each individual survey question. the survey response rate was 79%. table 1 depicts average response differences for each question before and after the presentation. positive differences between the preand post-surveys indicated the intervention improved attitudes, perceptions, and behaviors of outdoor workers regarding photoprotection and occupational skin cancer risk. outdoor occupational workers reported a better understanding of the risks of uv exposure and a greater willingness to engage in sun-protective practices following the brief educational intervention. this change in knowledge represents an approximately 14.4% ± 5.8% increase in participant agreement with statements on photoprotection and skin cancer following an educational intervention. the results of our survey-based quality improvement study suggest outdoor occupational workers may benefit from brief educational interventions regarding photoprotection and skin cancer risk. with an average pre-presentation question score of 3.01 and post-presentation score of 3.73, participating individuals reported a better understanding of the risks of uvr exposure, as well as a greater willingness to engage in photoprotective practices, following brief educational intervention. two-sample paired t-test performed for each of the 10 questions was statistically significant with a p <0.05 suggesting community-based education efforts may improve awareness regarding photoprotection and skin cancer risk, and ultimately mitigate behavior. the reproducible results of our, and other such studies, suggest a role for sun safety education in changing the behaviors and attitudes of at-risk individuals toward skin cancer risk. methods results discussion skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 618 table 1. differences in survey scores before and after a brief educational presentation question pre-intervention (mean ± sd) post-intervention (mean ± sd) p-value (95% ci) 1 3.54 ± 1.20 4.19 ± 1.04 <0.0001* (0.51, 0.88) 2 2.11 ± 1.32 3.16 ± 1.46 <0.0001** (0.82, 1.27) 3 2.60 ± 1.59 3.39 ± 1.40 <0.0001† (0.87, 1.39) 4 2.54 ± 1.46 3.63 ± 1.23 <0.0001* (0.815, 1.273) 5 2.69 ± 1.32 3.64 ± 1.24 <0.0001† (0.73, 1.19) 6 3.61 ± 1.32 4.02 ± 1.23 <0.0001* (0.23, 0.66) 7 3.41 ± 1.30 4.05 ± 1.10 <0.0001† (0.41, 0.86) 8 3.06 ± 1.45 3.99 ± 1.28 <0.0001** (0.69, 1.17) 9 2.92 ± 1.36 3.21 ± 1.54 0.0156** (0.05, 0.54) 10 3.62 ± 1.43 4.04 ± 1.22 0.0003** (0.815, 1.273) *indicates n=157. **indicates n=158. †indicates n=159 p-values less than 0.05 considered statistically significant. skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 619 while these interventions represent a costeffective means of improving outcomes and reducing morbidity in populations susceptible to developing skin cancer, the attitudes and perceptions of outdoor workers need to be taken into consideration when developing preventative interventions.1 a qualitative study published by rocholl et al. in the journal of occupational health sought to better understand these attitudes through problem-centered qualitative interviews with male outdoor workers.1 results of this study found a universal underestimation of perceived skin cancer risk and heterogenous attitudes toward photoprotection.1 while this has been demonstrated in other studies, rocholl et al. used qualitative interviews to analyze the reasons behind these findings. the results demonstrated that participants struggled with the feasibility of photoprotection in large part due to their working environment, citing long-sleeved shirts and long trousers were considered problematic.1 while headgear was commonly worn and sunscreen use was reported, interviewees understanding of proper application, including reapplying, was limited.1 the importance of these findings is paramount to developing appropriate educational intervention measures that may address individuals’ knowledge-gaps related to skin cancer. in order to be effective, educational interventions should be tailored to the individual needs and attitudes of the outdoor workers to best facilitate the implementation of photoprotective measures. the results of our survey-based quality improvement study suggest outdoor occupational workers may significantly benefit from brief educational interventions regarding photoprotection and skin cancer risk. these interventions are easily reproducible and represent a cost-effective means of improving outcomes and reducing mortality in vulnerable populations. a limitation in our study is the assessment of attitudes immediately after administration of the educational program; further research is needed to assess the longitudinal impact of these educational interventions. future studies may choose to introduce photoprotective measures on worksites and explore the effectiveness of these interventions on the behavior of outdoor workers. conflict of interest disclosures: none funding: none corresponding author: isabella aldana 707 richard arrington jr blvd s birmingham, al 35233 phone: 205-914-5535 email: ialdana@uab.edu references: 1. zink a, wurstbauer d, rotter m, wildner m, biedermann t. do outdoor workers know their risk of nmsc? perceptions, beliefs and preventive behaviour among farmers, roofers and gardeners. j eur acad dermatol venereol. 2017;31:1649‐1654. 2. rocholl, m., ludewig, m., john, s. m., bitzer, e. m., & wilke, a. (2020). outdoor workers' perceptions of skin cancer risk and attitudes to sun-protective measures: a qualitative study. journal of occupational health, 62(1), e12083 3. trakatelli, m., barkitzi, k., apap, c., majewski, s., de vries, e., & epiderm group (2016). skin cancer risk in outdoor workers: a european multicenter case-control study. journal of the european academy of dermatology and venereology : jeadv, 30 suppl 3, 5–11. 4. sena js, girão rj, carvalho sm, tavares rm, fonseca fl, silva pb, barbosa mc. occupational skin cancer: systematic review. rev assoc med bras (1992). 2016 mayjun;62(3):280-6. doi: 10.1590/18069282.62.03.280. pmid: 27310554. 5. zink a, schielein m, wildner m, rehfuess ea. 'try to make good hay in the shade – it won't conclusion skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 620 work!' a qualitative interview study on the perspectives of bavarian farmers regarding primary prevention of skin cancer. br j dermatol. 2019;180:1412‐1419. skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 415 brief article messenger rna-1273 moderna covid-19 vaccination as potential trigger for case of new onset pemphigus vulgaris sara holt, do1, abigail l. meckley, do2, taylor harp, do2, david esguerra, do, faad1 1 hca healthcare/usf morsani college of medicine gme programs, largo medical center, largo, fl 2 rocky vista university college of osteopathic medicine, parker, co with the ongoing covid-19 pandemic, there have been many reports of suspected dermatologic manifestations both from the virus and the vaccine, however, autoimmune bullous disorders following vaccination are less well described.1 pemphigus vulgaris (pv) is an autoimmune bullous disease of the skin and mucous membranes that has many known triggers, including vaccination.2 here we describe a case of new onset pv following covid-19 vaccination with the mrna-1273 (moderna) vaccine. a 67-year-old vietnamese female presented to the outpatient dermatology clinic with flaccid bullae and erosions involving the trunk and oral mucosa (figure 1a and 1b) five days after receiving the second dose of the mrna-1273 (moderna) vaccine. prior to vaccination, this patient was in her usual state of health and denied any significant medical history, medications or known allergies. histology of lesional skin showed a suprabasilar intraepidermal acantholytic blister consistent with pv. direct immunofluorescence demonstrated linear and granular igg and c3 deposition in the lower two thirds of the epithelial strata. lastly, enzyme-linked immunosorbent assay (elisa) detected antibodies to desmoglein 1 and 3 (128 and 36 u/ml, respectively). these clinical and laboratory findings confirmed the diagnosis of pv, and the patient was initiated on systemic therapy with oral prednisone and mycophenolate mofetil, leading to significant improvement in abstract as vaccination against covid-19 remains a worldwide initiative, so does describing its associated adverse effects. while there have been many reports detailing various dermatologic adverse events, autoimmune bullous disorders following vaccination are less well described.1 pemphigus vulgaris (pv) is an autoimmune bullous disease of the skin and mucous membranes that has many known triggers, including vaccination.2 to our knowledge, there are at least six cases of pemphigus vulgaris developing following sars-cov-2 vaccination.3 here we describe a case of new onset pv following covid-19 vaccination with the mrna-1273 (moderna) vaccine. because this disease carries significant morbidity and mortality, we hope this report serves as a reminder that while vaccination remains a global priority, continued documentation and recognition of novel vaccination side effects by clinicians is essential. introduction case report https://www.zotero.org/google-docs/?l1kf2v https://www.zotero.org/google-docs/?l1kf2v skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 416 her clinical condition after approximately six months of therapy. figure 1a. pemphigus vulgaris involving the back. figure 1b. pemphigus vulgaris involving the chest. pv is an acquired autoimmune bullous disease of the skin and mucous membranes that involves an immune response to desmosomal proteins of the skin, desmoglein 1 and 3, manifesting clinically as flaccid bullae and erosions in a mucocutaneous distribution. although the etiology of pv remains unclear, onset secondary to vaccination has been reported, including vaccines against influenza, typhoid, rabies, hepatitis b, tetanus, diphtheria, and anthrax.2 with the ongoing covid-19 pandemic, a massive number of individuals have received the vaccination globally, which has resulted in the report of a number of cutaneous manifestations, however autoimmune disorders like pv are less well described.1 to our knowledge, there are at least six cases of pv developing following sars-cov-2 vaccination,3 however this number may be higher according to the vaccine adverse events reporting system (vaers). co-managed by the centers for disease control and the u.s. food and drug administration, vaers (https://vaers.hhs.gov) accepts and analyzes reports of adverse events after a person has received a vaccination.4 there are at least 20 reported cases of pemphigus claimed to be associated with the mrna-1273 (moderna) vaccine, however no cause-andeffect relationship has been established.4 in this case, the development of pv following covid-19 vaccination with the mrna-1273 (moderna) vaccine may be coincidental, however the following factors suggest a relationship may exist: the time interval between vaccination and symptom onset, successful response to standard treatment, and lack of other risk factors such as drug intake, self or family history of autoimmune disorder, recent infection or known malignancy. while the patient described in this case presented with new onset pv following covid-19 vaccination, a causal association between the mrna covid-19 vaccine and discussion conclusion https://www.zotero.org/google-docs/?t3dh4s https://vaers.hhs.gov/ skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 417 pv needs further investigation. as vaccination remains a global initiative, continuing to record vaccine related events will help to better define potential causal relationship with pv and other potential side effects. despite potential risks of triggering or exacerbating cutaneous pathologies, we recommend continued administration of the mrna covid-19 vaccination in the appropriate clinical scenario in order to curb the current pandemic. conflict of interest disclosures: none funding: none corresponding author: sara holt, do 10047 nassau ct seminole, fl 33776 phone: 303-910-9243 email: sara.andrews@colorado.edu references: 1. mcmahon de, amerson e, rosenbach m, et al. cutaneous reactions reported after moderna and pfizer covid-19 vaccination: a registry-based study of 414 cases. j am acad dermatol. 2021;85(1):46-55. https://doi:10.1016/j.jaad.2021.03.092 2. solimani f, mansour y, didona d, dilling a, ghoreschi k, meier k. development of severe pemphigus vulgaris following sars-cov-2 vaccination with bnt162b2. j eur acad dermatol venereol. 2021;35(10):e649-e651. doi:10.1111/jdv.17480 3. calabria e, canfora f, mascolo m, varricchio s, mignogna md, adamo d. autoimmune mucocutaneous blistering diseases after sarscov-2 vaccination: a case report of pemphigus vulgaris and a literature review. pathol res pract. 2022 apr;232:153834. doi: 10.1016/j.prp.2022.153834 4. united states department of health and human services (dhhs), public health service (phs), centers for disease control (cdc) / food and drug administration (fda), vaccine adverse event reporting system (vaers) 1990 12/03/2021, cdc wonder on-line database. accessed at http://wonder.cdc.gov/vaers.html on dec 12, 2021 https://www.zotero.org/google-docs/?ubwyw4 https://www.zotero.org/google-docs/?ubwyw4 https://www.zotero.org/google-docs/?ubwyw4 https://www.zotero.org/google-docs/?ubwyw4 https://www.zotero.org/google-docs/?ubwyw4 https://www.zotero.org/google-docs/?ubwyw4 https://www.zotero.org/google-docs/?ubwyw4 https://www.zotero.org/google-docs/?ubwyw4 https://www.zotero.org/google-docs/?ubwyw4 https://www.zotero.org/google-docs/?ubwyw4 https://www.zotero.org/google-docs/?ubwyw4 https://www.zotero.org/google-docs/?ubwyw4 https://www.zotero.org/google-docs/?ubwyw4 https://www.zotero.org/google-docs/?ubwyw4 https://www.zotero.org/google-docs/?ubwyw4 https://www.zotero.org/google-docs/?ubwyw4 powerpoint presentation presented at 2021 fall clinical dermatology conference, las vegas, nv, usa, october 21–24, 2021 long-term safety and efficacy of roflumilast cream 0.3% in adult patients with chronic plaque psoriasis: results from a 52-week, phase 2b open-label study • 94% of aes were rated mild or moderate • 97% of aes were unrelated or unlikely to be related to treatment as determined by the investigator • rates of gastrointestinal and psychiatric aes were low • ≥97% of patients had no evidence of irritation per physician assessment at each visit conclusions • patients with chronic plaque psoriasis need topical treatments that provide effective control of psoriasis with low incidence of side effects that can be used for long-term treatment • in this phase 2 long-term safety study, roflumilast cream, an investigational, once-daily, nonsteroidal topical pde-4 inhibitor, was well-tolerated with no new safety signals – rates of discontinuations due to aes and lack of efficacy were low • durable efficacy was observed and the effect was maintained through 52 weeks of treatment in this long-term safety study and up to 64 weeks including the phase 2b study – similar durability of effect was observed in patients with intertriginous area involvement • once-daily roflumilast cream is a promising novel therapy for treating plaque psoriasis linda stein gold,1 melinda j. gooderham,2 kim a. papp,3 laura k. ferris,4 mark lebwohl,5 david n. adam,6 javier alonso-llamazares,7 h. chih-ho hong,8 steven e. kempers,9 leon h. kircik,10 wei jing loo,11 walter k. nahm,12 daniel stewart,13 matthew zirwas,14 patrick burnett,15 robert c. higham,15 lynn navale,15 david r. berk15 1henry ford medical center, detroit, mi, usa; 2skin centre for dermatology, probity medical research and queen’s university, peterborough, on, canada; 3probity medical research and k. papp clinical research, waterloo, on, canada; 4university of pittsburgh, department of dermatology, pittsburgh, pa, usa; 5icahn school of medicine at mount sinai, new york, ny, usa; 6cca medical research, probity medical research and temerty faculty of medicine, university of toronto, toronto, on, canada; 7driven research llc, coral gables, fl, usa; 8probity medical research and university of british columbia, department of dermatology and skin science, surrey, bc, canada; 9minnesota clinical study center, fridley, mn, usa; 10icahn school of medicine at mount sinai, new york, ny, indiana medical center, indianapolis, in, physicians skin care, pllc, louisville, ky, and skin sciences, pllc, louisville, ky, usa; 11dermeffects, london, on, canada; 12university of california, san diego, school of medicine, san diego, ca, usa; 13michigan center for skin care research, clinton township, mi, usa; 14dermatologists of the central states, probity medical research, and ohio university, bexley, oh, usa; 15arcutis biotherapeutics, inc., westlake village, ca, usa references 1. dong c, et al. j pharmacol exp ther 2016;358:413-422. 2. lebwohl mg, et al. n engl j med 2020;383:229-239. acknowledgements • this study was supported by arcutis biotherapeutics, inc. • thank you to the investigators and their staff for their participation in the trial • we are grateful to the study participants and their families for their time and commitment • writing support was provided by by christina mcmanus, phd, alligent biopharm consulting llc, and funded by arcutis biotherapeutics, inc. disclosures lsg, mg, kap, lkf, ml, dna, ja-l, hch, sek, lhk, wjl, wkn, ds, and mz are investigators and/or consultants for arcutis biotherapeutics, inc. and received grants/research funding and/or honoraria; pb, rch, ln, and drb are or were employees of arcutis biotherapeutics, inc. additional disclosures provided on request. introduction • topical treatment options for chronic plaque psoriasis lack products that are safe with long-term usage, are well tolerated, and are used as single agents over the entire body • roflumilast cream, a phosphodiesterase-4 (pde-4) inhibitor that is more potent than other pde-4 inhibitors,1 is under investigation as a once-daily, nonsteroidal, topical treatment for psoriasis • in a phase 2b randomized, double-blind, 12-week trial of 331 adults with chronic plaque psoriasis, roflumilast cream once daily was found to be superior to vehicle cream and was well tolerated2 • this multicenter, open-label, 52-week study was also conducted to assess long-term safety of roflumilast 0.3% cream in patients with chronic plaque psoriasis results figure 2. patient disposition ae: adverse event. high completion rate with low rate of discontinuations due to aes or lack of efficacy overall, n=332 enrolled cohort 1 (n=230) + cohort 2 (n=102) completed study n=244 (73.5%) discontinued, n=88 (26.5%) withdrawal: n=36 (10.8%) lost to follow-up: n=34 (10.2%) lack of efficacy: n=3 (0.9%) ae: n=13 (3.9%) other: n=2 (0.6%) figure 1. study design *excludes scalp, palms, soles. bsa: body surface area; iga: investigator global assessment; qd: once daily; pasi: psoriasis area severity index; sae: serious adverse event; teae: treatment-emergent adverse event. roflumilast cream 201 phase 2b (nct03638258)2 roflumilast cream 202 phase 2 long-term safety (nct03764475) eligibility • diagnosis of at least mild plaque psoriasis • age ≥18 years • 2-20% bsa* roflumilast cream 0.3% qd roflumilast cream 0.15% qd vehicle qd endpoints • primary: safety – occurrence of teaes – occurrence of saes • secondary: efficacy – iga clear or almost clear skin – intertriginous-iga clear or almost clear skin – pasi – bsa 12 weeks ra nd om iz at io n 1:1:1 n=331 eligibility • diagnosis of at least mild plaque psoriasis for at least 6 months • age ≥18 years • 2-25% bsa* cohort 1 (rollovers) roflumilast cream 0.3% qd 52 weeks cohort 2 (naïve) roflumilast cream 0.3% qd completed study 201 through 12 weeks table 1. baseline disease characteristics cohort 1 total (n=230) cohort 2 total (n=102) overall total (n=332) bsa, mean % 6.2 6.6 6.3 pasi, mean 7.2 6.8 7.1 iga score, n (%) 1 (almost clear) 8 (3.5) 0 (0.0) 8 (2.4) 2 (mild) 51 (22.2) 17 (16.7) 68 (20.5) 3 (moderate) 156 (67.8) 78 (76.5) 234 (70.5) 4 (severe) 15 (6.5) 7 (6.9) 22 (6.6) intertriginous involvement (i-iga ≥2) i-iga, n (%) 2 (mild) 19 (8.3) 12 (11.8) 31 (9.3) 3 (moderate) 17 (7.4) 12 (11.8) 29 (8.7) 4 (severe) 2 (0.9) 0 (0.0) 2 (0.6) baseline is defined as the last observation prior to the first dose of roflumilast cream in either the arq-151-201 or arq-151-202 study. bsa: body surface area; iga: investigator global assessment; i-iga: intertriginous investigator global assessment; pasi: psoriasis area and severity index. patients achieving iga success (iga = 0/1 plus a 2-grade improvement) figure 4. the proportion of patients achieving iga status of ‘clear’ or ‘almost clear’ with roflumilast was consistent over time iga: investigator global assessment. • of patients receiving roflumilast cream 0.3% in the parent trial who achieved iga of clear/almost clear at 12 weeks and continued in the open-label trial, 66.7% achieved iga of clear/almost clear at 64 weeks or their last visit 25.7 34.7 31.9 28.7 34.8 0 10 20 30 40 50 60 70 80 90 100 week 16 (n=218) week 24 (n=202) week 36 (n=182) week 48 (n=171) week 64 (n=158) pa ti en ts , % 17.2 40 34.5 36.7 39.5 0 10 20 30 40 50 60 70 80 90 100 week 4 (n=99) week 12 (n=95) week 24 (n=87) week 36 (n=79) week 52 (n=81) pa ti en ts , % cohort 1 (rollovers) cohort 2 (naïve) time on treatment v patients achieving iga success (iga = 0/1 plus a 2-grade improvement) figure 3. roflumilast provided durable improvement in iga no imputation of missing values. baseline is defined as the last observation prior to the first dose of arq-151 cream in either the arq-151-201 or arq-151-202 study. iga: investigator global assessment. 0 10 20 30 40 50 60 70 80 90 100 2 4 6 8 12 16 24 36 48 64 pa ti en ts , % roflumilast 0.3% (201) roflumilast 0.15% (201) vehicle (201) roflumilast 0.3% (202) study 2012 study 202 – all patients received roflumilast 0.3% n 331331 218 182202 171 158331 331 331 time on treatment • among all rollover groups, iga success was between 33% and 37%, and exceeded that observed among these patients at week 12 of the parent study patients achieving i-iga success (i-iga = 0/1 plus a 2-grade improvement) cohort 2 (naïve)† figure 5. roflumilast provided consistent improvement of i-iga‡ †cohort 1 not shown because i-iga added as study amendment and numbers of patients evaluated are very small at each timepoint; ‡collected post-baseline for patients with a severity of at least mild. i-iga: intertriginous-area investigator global assessment. 42.9 60.0 60.0 56.3 66.7 0 10 20 30 40 50 60 70 80 90 100 week 4 (n=21) week 12 (n=20) week 24 (n=20) week 36 (n=16) week 52 (n=15) pa ti en ts , % table 2. summary of aes (safety population) teae, n (%) cohort 1 total (n=230) cohort 2 total (n=102) overall total (n=332) patients with any teae 104 (45.2) 60 (58.8) 164 (49.4) patients with any treatment-related teae 7 (3.0) 5 (4.9) 12 (3.6) patients with any sae 10 (4.3) 2 (2.0) 12 (3.6) any treatment-related sae 0 (0) 0 (0) 0 (0) patients who discontinued study drug due to ae 11 (4.8) 2 (2.0) 13 (3.9) teae defined as event with an onset on or after the date of the first study drug application in arq-151-202 study. ae: adverse event; sae: serious adverse event; teae: treatment-emergent adverse event. table 3. most common aes (>2% overall) teae, n (%) cohort 1 total (n=230) cohort 2 total (n=102) overall total (n=332) upper respiratory tract infection/viral urti 14 (6.1) 8 (7.8) 22 (6.6) urinary tract infection 9 (3.9) 4 (3.9) 13 (3.9) nasopharyngitis 8 (3.5) 5 (4.9) 13 (3.9) sinusitis/chronic sinusitis 3 (1.3) 6 (5.9) 9 (2.7) hypertension/essential hypertension 8 (3.5) 1 (1.0) 9 (2.7) arthralgia 7 (3.0) 1 (1.0) 8 (2.4) back pain 5 (2.2) 2 (2.0) 7 (2.1) cough 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pruritus brian berman, md, phd; mark nestor, md, phd center for clinical and cosmetic research and university of miami miller school of medicine introduction atopic dermatitis (ad) is a chronic inflammatory skin disease characterized by pruritus. it affects up to 20% of children and 3% of adults worldwide, and its prevalence is increasing.1 the impact of pruritus in ad can range from mildly distressing to completely disabling.2 hypochlorous acid (hocl) has been identified as a treatment for pruritus.3 there are 2 mechanisms by which hocl may reduce pruritus: 1) by its microbicidal qualities, particularly in the case of staphylococcus aureus; and 2) by its antiinflammatory qualities, which help reduce the activity of histamine, leukotriene b4, and interleukin-2, all of which contribute to the pathophysiology of itch.4-7 here we present the results of a 3-day study designed to evaluate the effect of hocl on pruritus in patients with ad. the study was conducted according to the protocol and in compliance with good clinical practice (gcp) and other applicable regulatory requirements. this investigator blinded randomized phase 2 72-hour study investigated the antipruritic effect of hocl in patients diagnosed with ad. subjects were enrolled into the study if they had ad as defined by the hanifin criteria and had a score of >2 on an itch severity scare (0-4). 30 subjects were enrolled over the course of the study, with 20 randomized to the treatment group (hocl), and 10 randomized to the untreated control group. subjects who were randomized to the treatment group were instructed to use hocl bid or prn for 72-hours while recording the date and time of applications in a study diary. subjects randomized to the untreated group received no treatment and were only instructed to come to follow-up visits for study-specific assessments. the 3 primary measures used in this study were the participant global assessment (pga), investigator global assessment (iga), and vas itch score (indicated by a 154 mm line). pga was defined as the mean of five 5-point ordinal scales (0-none, 4-severe) for subject rated overall irritation, peeling, stinging, burning, and itching. the iga was defined as the mean of eight 5-point ordinal scales (0-4, none-severe) for erythema, desquamation, lichenification, overall irritation, excoriation, and subject queried stinging, burning and itching. the vas itch score was defined as the number of millimeters from the left side of a line (154 mm in length) that indicates their level of itching (0 mm no itching to 154 mm most itching). along with the 3 primary measures, incidence of unexpected adverse events (aes) and serious adverse events (saes) and incidence of local skin reactions leading to discontinuation were recorded as well. measurements were taken at baseline, 24-hours, and 72-hours post treatment. photographic evidence was used to confirm evaluations. material and methods table 1. baseline investigator elicited itch score (0-4) results thirty subjects were enrolled into the study in a 2:1 ratio (treated:untreated), and 29 were included in the final analysis. the mean vas itch score between the 2 groups were similar at baseline (table 1). mean change in pga and iga between baseline and 72-hours were both shown to be significantly different, with a decrease (improvement) in favor of the treatment group (pga: p-value=0.128; iga: p-value=0.012) (figure 1). the mean itch vas scores between the treated and untreated groups were significantly different between baseline and 72-hours post application, with the percent mean change shown to be significantly lower in the treated group (figure 2). at the conclusion of the study, subjects in both groups were separated into those who had less itch (difference in itch between baseline and 72 hours was positive), same itch (difference in itch between baseline and 72 hours was equal to zero), or more itch at 72 hours (difference in itch between baseline and 72 hours was negative) (figure 3). the analysis showed 73.7% of the subjects in the treated and 30.0% of the subjects in the untreated group experienced a reduction in itching between baseline and 72 hours post application. there were no treatment related discontinuations or saes. one subject reported mild to moderate transient facial dryness which spontaneously resolved when that subject applied the gel to the face. figure 4 shows photographic evidence of a significant decrease in ad characteristics (erythema, dryness, desquamation) at 72 hours. figure 1. mean change in pgad3-d1 and igad3-d1 with and without treatment with hocl gel x 3 day -0.25 -0.2 -0.15 -0.1 -0.05 0 0.05 0.1 -0.158 -0.237 0.08 -0.013 hocl treated x 3d untreated x 3d 'pga 'iga p<0.128 figure 2. mean % change in itch vas with and without treatment with hocl gel x 3 days conclusions this study demonstrated that hocl leads to a significant reduction in itching associated with ad in as little as 72 hours. additionally, the twice daily regimen was manageable and easy to follow, as demonstrated by a high rate of compliance. hocl is effective over a short period of time with few doses needed. this is a cost efficient and effective method for improving the symptom of pruritus in patients with ad. figure 3. effect of treatment with hocl gel x3 days on itch in atopic dermatitis figure 4. subject treated with hocl before (left) and 72 hours after (right) treatment references 1. nutten s. atopic dermatitis: global epidemiology and risk factors. ann nutr metab. 2015;66(suppl 1):8-16. 2. elmariah sb. adjunctive management of itch in atopic dermatitis. derm clin. 2017;35(3):373-394. 3. pelgrift ry, friedman aj. topical hypochlorous acid (hocl) as a potential treatment of pruritus. curr derm rep. 2013; 2:181–190. 4. garibyan l, rheingold cg, lerner ea. understanding the pathophysiology of itch. dermatol ther. 2013;26(2):84–91. 5. greaves mw. pathogenesis and treatment of pruritus. curr allergy asthma rep. 2010;10(4):236–42. 6. yosipovitch g, papoiu ad. what causes itch in atopic dermatitis? curr allergy asthma rep. 2008;8(4):306–11. 7. friedman aj, cash k, berman b. hypochlorous acid is antiinf lammatory and immunomodulatory. poster. presented at the winter clinical dermatology conference, kauai, hi, january 18, 2013. supported in part by onset and intraderm. baseline at 72-hours day 2 day 3 change in vas score 0-72 hours/baseline vas score x 100% -59.50% -84.50% fc17posterintradermbermananinvestigatorblindedstudy.pdf skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 455 brief articles adult-onset still’s disease presenting as an atypical cutaneous eruption cory kosche bs1, lida zheng md1, lauren guggina md1 1department of dermatology, northwestern university, feinberg school of medicine, chicago, il adult onset still’s disease (aosd) is a rare disorder characterized by spiking fevers, a characteristic evanescent eruption, and arthralgias.1 serum studies classically show an elevated ferritin and leukocytosis (classically neutrophilia) without an elevated ana or rheumatoid factor.2 there are variable reports of incidence and prevalence, some suggesting a bimodal age of onset peaking at 15-25 and again at 3646.2 here, we report the case of a female in her 40s with adult-onset still’s disease with an atypical eruption. a white female in her 40s presented with a 2-year history of a pruritic eruption, 1 year history of arthralgias, and recent night sweats with daily fevers up to 102ºf. she had been previously diagnosed with undifferentiated connective tissue disease vs dermatomyositis and was treated with courses of topical and oral steroids, hydroxychloroquine, and mycophenolate mofetil, all without significant improvement in her symptoms. physical exam revealed brightly erythematous thin plaques with fine scaling, many with linear accentuation, located over the trunk and extremities, with some involvement of her face and scalp, she also had scattered edematous 2-6 mm erythematous transient papules on the trunk and extremities (figure 1). notably, her introduction case report abstract adult-onset still’s disease classically presents with high fevers, arthralgias, leukocytosis, and an evanescent eruption. there are, however, a known subset of patients who develop an atypical eruption with persistent erythematous to violaceous papules and plaques. here, we present the case of a white female in her 40s who presented with 2 years of spiking fevers, arthralgias, and a fixed pruritic eruption with erythematous plaques with overlying scale and linear accentuation. she was initially treated with oral prednisone, anakinra, and methotrexate. due to persistent symptoms, she was switched to adalimumab with significant relief of symptoms. prompt recognition of adult-onset still’s disease with this atypical eruption may help prevent delayed or missed diagnosis and allow for early, appropriate intervention. skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 456 eyelids were clear and nailfolds were within normal limits. she had leukocytosis (28k/l [3.5-10.5]) with neutrophilia. aldolase (24.6u/l [<8.2]) and ferritin (1379.9ng/ml [11-37]) were elevated. ana, rheumatoid factor, ccp, c3/c4, cpk, ssa, ssb, antijo, anti-sm were all within normal limits. punch biopsies of representative lesions on the abdomen and right lower extremity were performed (figure 2). histopathological analysis revealed margination of neutrophils with marked perivascular mononuclear cell infiltrate with eosinophils and occasional dyskeratotic keratinocytes within the epidermis. given her constellation of symptoms, elevated ferritin, leukocytosis, and histopathologic findings, she was diagnosed with aosd. she was initially treated with oral prednisone 40mg daily, which was increased two weeks later to 60mg daily for persistent symptoms with the addition of anakinra 100mg daily. though she experienced moderate relief of symptoms, her rash and arthralgias persisted. one month later, methotrexate was added at 12.5mg weekly and gradually increased to 20mg weekly to allow for a prednisone taper. again, her rash and arthralgias remained and any mild prednisone taper caused a flare of symptoms. thus, anakinra was deemed ineffective, discontinued, and adalimumab, 40mg every 2 weeks, was started, instead. after two months, she was able to completely taper off the prednisone and her rash and fevers have resolved with only occasional persistent arthralgias. figure 1a. anterior trunk demonstrating photoaccentuated erythematous plaques and papules, some with overlying scale. figure 1b. upper back and flanks demonstrating erythematous plaques and papules with linear accentuation and overlying scale. additionally, edematous erythematous transient papules can be seen in the mid and lower back. skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 457 figure 2. hematoxylin and eosin (10x) stained specimen demonstrating a marked neutrophilic infiltrate and scattered dyskeratotic necrotic keratinocytes in the epidermis. to diagnosis aosd, the classic yamaguchi criteria define 4 major and 5 minor criteria.3 diagnosis requires meeting 5 criteria, with at least 2 major. major criteria: 1. high fever >1 week 2. arthralgias > 2 weeks 3. granulocytic leukocytosis > 10,000/µl 4. characteristic non-pruritic salmon colored (evanescent) rash minor criteria: 1. sore throat 2. lymphadenopathy 3. hepatomegaly or splenomegaly 4. abnormal liver function tests 5. negative tests for rf and ana histopathologic analysis of the classic evanescent aosd eruption reveals a neutrophilic infiltrate below an unremarkable epidermis, resembling neutrophilic dermatosis.6 however, in atypical cutaneous eruptions of aosd, often described as persistent pruritic eruptions, histopathology may also show dyskeratotic keratinocytes in the upper epidermis.6 clinically, this patient had a persistent scaling linear eczematous eruption, accentuated in photo distributed areas, as well as an urticarial “evanescent” eruption. her photo-accentuated eruption of the face and chest, an initial non-specific biopsy and an elevated aldolase raised suspicion for dermatomyositis. however, she did not have a positive ana, muscle weakness, or characteristic cutaneous findings (gottron’s papules, eyelid involvement, nail fold changes).7 notably, numerous cases of aosd with atypical cutaneous eruptions have been reported.8 the most common findings included erythematous, brown, or violaceous persistent papules and plaques, often in conjunction with the classic evanescent pattern.8 linear configurations, photoaccentuation, and dermatomyositis-like eruptions have all been reported.8 while the exact etiology of aosd is unknown, there can be an association with an infectious trigger or underlying malignancy.2 malignancies have been reported to occur up to 6 years later and most commonly include lymphoma, breast, lung, and thyroid cancer.8 there remains no clear association between classic or atypical eruptions and malignancy.2,8 as with dermatomyositis, patients should have age appropriate cancer screening. this patient had a normal mammogram and ca-125 was within normal limits. the treatment of aosd is typically initiated with non-steroidal anti-inflammatory drugs (nsaids) and topical, oral, or iv pulsed corticosteroids.2 as in this case, disease persistence despite corticosteroid therapy discussion skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 458 often requires the addition of disease modifying anti-rheumatic drugs such as methotrexate, il-1 inhibitors, or tnf-a inhibitors.2 this case is representative of aosd with an atypical cutaneous eruption and histopathological findings specific for aosd. our case highlights that aggressive treatment with multiple agents is required and high clinical suspicion for this diagnosis is warranted, even with atypical cutaneous findings. conflict of interest disclosures: none funding: none corresponding author: lauren guggina, md northwestern university 676 n saint clair st, ste 1600 chicago, il 60611 tel: (312) 695-8106 fax: (312) 695-0537 email: lauren.guggina@northwestern.edu references: 1. bywaters eg. still's disease in the adult. annals of the rheumatic diseases. 1971;30(2):121-133. 2. efthimiou p, paik pk, bielory l. diagnosis and management of adult onset still’s disease. annals of the rheumatic diseases. 2006;65(5):564-572. 3. yamaguchi m, ohta a, tsunematsu t, et al. preliminary criteria for classification of adult still's disease. the journal of rheumatology. 1992;19(3):424-430. 4. fautrel b, zing e, golmard j-l, et al. proposal for a new set of classification criteria for adultonset still disease. medicine. 2002;81(3):194200. 5. kawaguchi y, terajima h, harigai m, hara m, kamatani n. interleukin-18 as a novel diagnostic marker and indicator of disease severity in adultonset still's disease. arthritis & rheumatism. 2001;44(7):1716-1717. 6. qiao j, zhou s, li s, et al. histopathological diagnosis of persistent pruritic eruptions associated with adult-onset still's disease. histopathology.0(0). 7. callen jp. dermatomyositis. the lancet. 2000;355(9197):53-57. 8. sun nz, brezinski ea, berliner j, et al. updates in adult-onset still disease: atypical cutaneous manifestations and associations with delayed malignancy. journal of the american academy of dermatology. 2015;73(2):294-303. conclusion mailto:lauren.guggina@northwestern.edu skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 217 research letter insurance coverage for phototherapy for vitiligo in comparison to psoriasis and atopic dermatitis fabiana c. p. s. lopes, md1, ammar m. ahmed, md1 1the university of texas at austin / dell medical school, division of dermatology, austin, tx vitiligo affects 0.4-2% of the population. phototherapy, specifically uvb, is considered a gold-standard treatment.1 uvb is administered in clinics or via home phototherapy (hpt) unit. although some insurances consider it investigational, hpt is more cost-effective and equally safe and efficacious than in-office phototherapy (iopt).2 multiple barriers to accessing phototherapy exist, including insurance coverage and other financial barriers. for psoriasis, for example, biologics, which are more expensive than phototherapy, have less stringent requirements for obtaining approval than iopt or hpt.3 financial barriers are particularly significant for hpt even though hpt reduces co-payments, travel expenses, and provider’s administrative costs compared to iopt.3 we sought to compare iopt and hpt insurance coverage for vitiligo with psoriasis and atopic dermatitis (ad).4 insurance plans from the texas department of insurance list, which lists the top 40 insurances by market-share in the state, and from the seton family of doctors managed care contract list, which lists plans our institution accepts, were included. information about phototherapy coverage was extracted via web search. only insurers that had relevant abstract objective: to compare in-office phototherapy and home phototherapy insurance coverage for vitiligo with psoriasis and atopic dermatitis. methods: information about phototherapy coverage in texas was extracted via web search. results: vitiligo is the only disease analyzed for which multiple insurances explicitly stated they do not cover in-office phototherapy, and it is also the least covered for home phototherapy. moreover, more insurances have more prerequisites to cover phototherapy for vitiligo than they do for psoriasis and atopic dermatitis. conclusions: our results show that insurance coverage of phototherapy in texas varies widely and that, compared to patients with psoriasis and atopic dermatitis, patients with vitiligo face higher insurance coverage barriers for phototherapy. as phototherapy is a safe and effective vitiligo treatment, efforts to produce greater parity in coverage between vitiligo and other dermatologic diseases are warranted. introduction methods skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 218 information attainable were included. most insurers disclose these policies are used as guidelines for decisions, but that final determinations are made on a case-by-case basis. for iopt, 14 carriers had information for at least one of the three skin disorders (see table 1). of those, 100% stated they provide coverage for psoriasis, 78% for ad, and only 50% for vitiligo. twenty-two percent explicitly stated they do not provide coverage for vitiligo. the remaining carriers do not have this information publicly available for vitiligo and ad. among the 7 insurances that cover iopt for vitiligo, 2 of them mandate more prerequisites from vitiligo patients than from psoriasis and ad patients, such as greater body surface area (bsa) involvement or specific anatomical site involvement. regarding hpt, 14 carriers had attainable information (see table 2). of those, 93% explicitly offer coverage for psoriasis, 50% for ad, and only 28% for vitiligo. forty three percent explicitly stated they do not provide coverage for vitiligo. among the 4 insurances covering hpt for vitiligo, two request more prerequisites from vitiligo patients than from psoriasis and ad patients; vitiligo patients need to have more than 30% of bsa involved while psoriasis patients need to have only more than 5% of bsa involved, with no minimum bsa for ad. insurance coverage of phototherapy in texas varies widely. vitiligo is the only disease analyzed for which multiple insurances explicitly stated they do not cover iopt, and it is also the least covered for hpt. moreover, more insurances have more prerequisites to cover phototherapy for vitiligo than they do for psoriasis and ad. vitiligo, psoriasis, and ad have comparable negative effects on quality-of-life, and effective treatment of each correlates with positive quality-of-life outcomes.5 our results show that compared to patients with psoriasis and ad, patients in texas with vitiligo face higher insurance coverage barriers for phototherapy. as phototherapy is a safe and effective vitiligo treatment, efforts to produce greater parity in coverage amongst the diseases are warranted. conflict of interest disclosures: none funding: none corresponding author: fabiana c. p. s. lopes md 14208 rountree ranch lane austin, tx 78717 phone: 734-747-4972 email: fabiana.castroportosilvalopes@ascensionexternal.org references: 1. mohammad, t.f., al-jamal, m., hamzavi, i.h., harris, j.e., leone, g., cabrera, r., et al. the vitiligo working group recommendations for narrow-band ultraviolet b light phototherapy treatment of vitiligo. j am acad dermatol. 2017;76(5), 879-888. doi:10.1016/j.jaad.2016.12.041. 2. dillon, j.p, ford, c., hynan, l.s., pandya, a.g. a cross‐sectional, comparative study of home vs in‐ office nb‐uvb phototherapy for vitiligo. photodermatol photoimmunol photomed. 2017;33(5), 282–283. doi:10.1111/phpp.12326. 3. smith, m.p., ly, k., thibodeaux, q., bhutani, t., nakamura, m. home phototherapy for patients results discussion conclusion skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 219 with vitiligo: challenges and solutions. clin cosmet investigat dermatol. 2019;12, 451–459. doi:10.2147/ccid.s185798. 4. kemény, l., varga, e., novak, z. advances in phototherapy for psoriasis and atopic dermatitis. expert rev clin immunol. 2019;15(11), 12051214. doi:10.1080/1744666x.2020.1672537. 5. ahmed, a., leon, a., butler, d.c., reichenberg, j. quality-of-life effects of common dermatological diseases. semin cutan med surg. 2013;32(2), 101–9. doi:10.12788/j.sder.0009. table 1 in-office phototherapy – is it considered medically necessary? carrier/disease vitiligo psoriasis atopic dermatitis aetna last review: 06/28/2021 yes, with prerequisites only if there is significant follicular pigmentation after 6 months of therapy. yes yes amerigroup last review: 08/13/2020 no information attainable yes yes bluecross blueshield of texas last review: 06/01/2021 yes, with prerequisites only when there has been a failure, intolerance, or contraindication to treatment with topical or systemic drug therapy. yes, with prerequisites only when there has been a failure, intolerance, or contraindication to treatment with topical or systemic drug therapy. yes, with prerequisites only when there has been a failure, intolerance, or contraindication to treatment with topical or systemic drug therapy. cigna last review: 09/15/2020 yes, with prerequisites only when either of the following criteria is met: vitiligo bsa involvement ≤ 10% with both of the following: failure, intolerance, or contraindication to at least one topical corticosteroid failure, intolerance, or contraindication to at least one topical calcineurin inhibitor vitiligo bsa involvement > 10% more than 200 treatment sessions of office-based phototherapy are considered not medically necessary. yes, with prerequisites only when there is failure, intolerance, or contraindication to conventional medical management. yes, with prerequisites only when there is failure, intolerance, or contraindication to conventional medical management. government employee health association last review: 02/16/2021 no information attainable yes no information attainable geisinger health plan last review: 04/2021 yes, with prerequisites only if it is not responsive to conservative therapies and when it affects: a. the skin of the head and/or neck area, or, b. other body areas in excess of 30% of skin surface yes, with prerequisites only if it is not responsive to conservative therapies. yes, with prerequisites only if it is not responsive to conservative therapies. humana last review: 01/28/2021 no yes, with prerequisites only when the following criteria are met: absence of contraindications listed in the coverage limitations section; and after failure of, intolerance to, or contraindication to treatment using conventional medical management yes, with prerequisites only when the following criteria are met: absence of contraindications listed in the coverage limitations section; and after failure of, intolerance to, or contraindication to treatment using conventional medical management medicare this is a longstanding national coverage determination. the no information attainable yes no information attainable skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 221 table 2. home-based phototherapy – is it considered medically necessary? carrier/disease vitiligo psoriasis atopic dermatitis aetna last review: 04/15/2021 no yes, with prerequisites only for persons with severe psoriasis with a history of frequent flares who are unable to attend on-site therapy or those needing to initiate therapy immediately to suppress psoriasis flares. yes, with prerequisites only for persons with atopic dermatitis (eczema) who are unable to attend on-site therapy. amerigroup last review: 08/13/2020 no yes, with prerequisites only when conditions a and b are met: when topical treatment alone has failed the treatment meets all the following criteria: 1. treatment is conducted under a physician's supervision with regularly scheduled exams; and 2. treatment is expected to be long term (3 months or longer); and 3. the individual meets any of the following: the individual is unable to attend officebased therapy due to a serious medical or physical condition (for example, confined to the home, leaving home requires special services or involves unreasonable risk); or office-based therapy has failed to control the disease, and it is likely that home-based therapy will be successful the individual suffers from severe psoriasis with a history of frequent flares, which require immediate treatment to control the disease. yes, with prerequisites only when conditions a and b are met: when topical treatment alone has failed the treatment meets all the following criteria: 1. treatment is conducted under a physician's supervision with regularly scheduled exams; and 2. treatment is expected to be long term (3 months or longer); and 3. the individual meets any of the following: the individual is unable to attend office-based therapy due to a serious medical or physical condition (for example, confined to the home, leaving home requires special services or involves unreasonable risk); or office-based therapy has failed to control the disease, effective date of this version has not been posted. molina healthcare last review: 06/19/2019 no yes, with prerequisites only when clinical documentation of inadequate symptom control, intolerance, or contraindication to conventional medical management. yes, with prerequisites only when clinical documentation of inadequate symptom control, intolerance, or contraindication to conventional medical management. oscar last review: 12/14/2020 yes yes yes scott & white health plan last review: 06/27/2019 no yes, with prerequisites only after conventional therapies have failed. yes, with prerequisites only after conventional therapies have failed for ad that is refractory. texas medicaid last review: 10/2020 yes yes yes tricare last review: 06/18/2020 yes yes yes united healthcare last review: 02/16/2021 no information attainable yes no information attainable skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 222 and it is likely that homebased therapy will be successful bluecross blueshield of texas last review: 06/01/2021 yes, with prerequisites only when the criterion for officebased phototherapy is met, and all the following are met: 1. improvement has been demonstrated with the use of uv treatments in the physician's office; and 2. patient can operate the home phototherapy unit, staying within prescribed periods of exposure, and the unit is expected to be used frequently (e.g., 3 times/week) on a long-term basis. yes, with prerequisites only when the criterion for office-based phototherapy is met, and all the following are met: 1. improvement has been demonstrated with the use of uv treatments in the physician's office; and 2. patient can operate the home phototherapy unit, staying within prescribed periods of exposure, and the unit is expected to be used frequently (e.g., 3 times/week) on a long-term basis. yes, with prerequisites only when the criterion for office-based phototherapy is met, and all the following are met: 1. improvement has been demonstrated with the use of uv treatments in the physician's office; and 2. patient can operate the home phototherapy unit, staying within prescribed periods of exposure, and the unit is expected to be used frequently (e.g., 3 times/week) on a long-term basis. cigna last review: 09/15/2020 yes, with prerequisites only when the criteria for officebased phototherapy are met with all the following: outpatient uvb phototherapy has been utilized, demonstrated to be beneficial, and is expected to be long-term; the device is not available without a prescription, and the device and treatment regimen are prescribed by a physician; individual is motivated and compliant to prescribed usage yes, with prerequisites only when the criteria for office-based phototherapy are met with all the following: outpatient uvb phototherapy has been utilized, demonstrated to be beneficial, and is expected to be long-term the device is not available without a prescription, and the device and treatment regimen are prescribed by a physician individual is motivated and compliant to prescribed usage yes, with prerequisites only when the criteria for office-based phototherapy are met with all the following: outpatient uvb phototherapy has been utilized, demonstrated to be beneficial and is expected to be longterm the device is not available without a prescription and the device and treatment regimen are prescribed by a physician individual is motivated and compliant to prescribed usage government employee health association last review: 06/14/2021 no information attainable yes, with prerequisites only with current prescription from physician and physician office notes with clinical documentation that includes: presence of generalized intractable psoriasis; dates of prior conservative treatments with objective clinical outcomes; and factors that justify treatment at home rather than at alternative outpatient sites no information attainable geisinger health plan last review: 04/2021 yes, with prerequisites only if all the following criteria are met: the panel is requested by a dermatologist; and the individual is under the requesting provider's supervision with regularly scheduled exams (patient is seen at least once a year); and treatment is expected to be ongoing or long term (e.g., greater than 4 months); and it affects: a. the skin of the head and/or neck area, or, b. other body areas in excess of yes, with prerequisites only if all the following criteria are met: the panel is requested by a dermatologist; and the individual is under the requesting provider's supervision with regularly scheduled exams (patient is seen at least once a year); and treatment is expected to be ongoing or long term (e.g., greater than 4 months); and the individual has psoriasis characterized by ≥ 5% of body surface area involved or disease involving crucial body areas such as the hands, feet, face, or genitals, and a therapeutic failure on, intolerance to, or contraindication to topical therapy yes, with prerequisites only if all the following criteria are met: the panel is requested by a dermatologist; and the individual is under the requesting provider's supervision with regularly scheduled exams (patient is seen at least once a year); and treatment is expected to be ongoing or long term (e.g., greater than 4 months); skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 223 30% of skin surface humana last review: 01/28/2021 no yes, with prerequisites only when the following criteria are met: individual is confined to the home or the condition is such that attending office based therapy would require considerable effort, impose significant hardship (e.g., lost work time, extended travel distance) or expose the individual to undesirable risk; and treatment is expected to be long-term (i.e., necessary for at least 12 months); and uvb phototherapy device size is the smallest size appropriate for the treatment area; and either of the following: psoriasis with a known history of frequent flares despite long-term conventional medical management (oral or topical medications) which require immediate uvb phototherapy for suppression, or psoriasis when a twomonth trial of office-based uvb therapy has proven effective no medicare last review: 05/05/2005 no information attainable yes, with prerequisites only for selected patients with generalized intractable psoriasis and should be determined whether medical and other factors justify treatment at home rather than at alternative sites, e.g., outpatient department of a hospital. no information attainable molina healthcare last review: 06/19/2019 no yes, with prerequisites only when the criteria are met for in-office phototherapy and: [all] in patients who are unable to receive phototherapy in an office setting; or for those patients that have difficulty in maintaining frequent office visits due to their medical condition or considerable distance in travel from home to office (e.g.,>45 minutes one way) yes, with prerequisites only when the criteria are met for in-office phototherapy and: [all] in patients who are unable to receive phototherapy in an office setting; or for those patients that have difficulty in maintaining frequent office visits due to their medical condition or considerable distance in travel from home to office (e.g.,>45 minutes one way) oscar last review: 01/01/2021 no no no scott & white health plan last review: 06/27/2019 no yes, with prerequisites only for persons with severe psoriasis with a history of frequent flares who are unable to attend on-site therapy or those needing to initiate therapy immediately to suppress psoriasis flares. the following conditions must be met: outpatient uvb phototherapy has been utilized, demonstrated to be beneficial and is expected to be long-term the device is not available without a prescription and the device and treatment regimen are prescribed by a physician no skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 224 the device, if a uv light booth, must require programming by the supplier using the physician script individual is motivated and compliant to prescribed usage superior health ambetter last review: 12/2020 no information attainable yes, with prerequisites only when: a. refractory psoriasis; and b. md justifies treatment at home versus alternate sites (e.g., outpatient department at hospital). panel lights should be considered if several discrete body areas can be treated individually. cabinet style should be reserved for extensive involvement > 54% of body surface area. no information attainable tricare last review: 06/18/2020 yes, with prerequisites only when prescribed by a physician. durable medical equipment (dme) is defined as an item that: can withstand repeated use; primarily and customarily serves a medical purpose; and generally, is not useful to an individual in the absence of an injury or illness. yes, with prerequisites only when prescribed by a physician. durable medical equipment (dme) is defined as an item that: can withstand repeated use; primarily and customarily serves a medical purpose; and generally, is not useful to an individual in the absence of an injury or illness. yes, with prerequisites only when prescribed by a physician. durable medical equipment (dme) is defined as an item that: can withstand repeated use; primarily and customarily serves a medical purpose; and generally, is not useful to an individual in the absence of an injury or illness. united healthcare last review: 06/14/2021 no information attainable yes, with prerequisites only with current prescription from physician and physician office notes with clinical documentation that includes: presence of generalized intractable psoriasis dates of prior conservative treatments with objective clinical outcomes; and factors that justify treatment at home rather than at alternative outpatient sites no information attainable skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 447 brief articles generalized pustular psoriasis in an adolescent treated with cyclosporine: a diagnostic and therapeutic challenge roya s. nazarian ba1, john nia md1, nikki vyas md1, garrett desman md1, lauren geller md1 1department of dermatology, icahn school of medicine at mount sinai, new york, ny generalized pustular psoriasis (gpp) is an uncommon and life-threatening variant of psoriasis that presents as an acute or chronic pustular eruption. gpp is especially rare in children and adolescents, accounting for only 0.5-0.6% of psoriasis cases in the pediatric population.1 the safety and efficacy of treatments in this age group is not well established, though case reports describe safe use of oral retinoids, methotrexate, and phototherapy.2 here we present the use of cyclosporine to treat gpp in an adolescent without adverse events. furthermore, we highlight clinical and histological features that can aid in the diagnosis of this rare childhood disease. a 15-year-old male with a past medical history significant for asthma and atopic dermatitis presented to the emergency room with a four-day history of rash, fever, and joint pain. he also reported a history of nausea and diarrhea 2 weeks prior to the onset of rash and fever. on examination he was noted to have conjunctival erythema, palatal petechiae, and pinpoint pustules on an erythematous introduction case report generalized pustular psoriasis (gpp) is rare in the pediatric population, accounting for only 0.5-0.6% of psoriasis cases in children. this presents a diagnostic and therapeutic challenge; biopsy is often required to differentiate gpp from similar entities such as acute generalized exanthematous pustulosis. we describe a case of gpp in a 15-year-old male presenting with widespread pustules, fever, and vital instability. the clinical presentation and biopsy results were consistent with a diagnosis of gpp. the patient was successfully treated with cyclosporine 3mg/kg/day. he was subsequently transitioned to 25 mg acitretin daily and remained in remission at the 9-month follow-up. we report this case to highlight available treatment options for gpp in the pediatric population and to underscore key clinical and histologic findings, which may aid dermatologists in proper diagnosis of this rare childhood disease. abstract skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 448 base on his neck, abdomen, and upper and lower extremities (figure 1 and 2). nikolsky sign was negative, though he reported burning of the eyes and extremities. vitals were significant for tachycardia to 103 beats per minute, hypotension to 100/49 mmhg, and fever to 101.3 °f. laboratory results were notable for a leukocytosis to 13.4/mm3 (4,500-11,000/mm3) with 74% polymorphic nuclear cells (54-62%) and an albumin of 2.9 g/dl (3.5-5.5 g/dl). liver function tests, calcium level, and esr were normal. a rapid strep test was negative. the differential diagnosis included acute generalized exanthematous pustulosis (agep), generalized pustular psoriasis, deficiency of the il-36r antagonist (ditra), and linear iga bullous disease. punch biopsies from the trunk and lower extremities demonstrated regular acanthosis and subcorneal pustules within the spinous layers of the epidermis with a diminished granular layer. the stratum corneum showed focal mounds of parakeratosis with neutrophils, mild spongiosis, and subcorneal pustules. the suprapapillary plates were attenuated. no eosinophils were noted. small, ectatic capillaries were present in the dermal papillae (figure 3a and 3b). direct immunofluorescence was negative. clinical and histologic findings were most consistent with gpp. cyclosporine 3mg/kg/day was initiated and the patient’s lesions began to desquamate the following day. as an outpatient, he was transitioned to acitretin 25mg daily and has been maintained on this for the past 9 months without any recurrence. figure 1. clinical presentation of left lower extremity on hospital day 1. physical exam was notable for pinpoint pustules coalescing in some areas into larger pustular bulla on a background of erythema on neck, truck and upper and lower extremities. skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 449 figure 2. clinical presentation of left lower extremity on hospital day 2. on day 2, the pustules became more confluent to form pustular lakes on the hands and lower extremities (figure 2), note the worsening pustular lesions that have enlarged and become more confluent in addition to pustular lake formation on the left lower extremity. figure 3a. hematoxylin and eosin, 10x; at low power the epidermis shows regular acanthosis and subcorneal pustules within the spinous layers. the granular layer is reduced. figure 3b. hematoxylin and eosin, 40x; the stratum corneum shows focal mounds of parakeratosis with neutrophils. mild spongiosis and subcorneal pustules are also present. the suprapapillary plates are attenuated and the stratum corneum shows focal parakeratotic scale with neutrophils. small, ectatic capillaries are present in the dermal papillae. skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 450 gpp, also known as von zumbusch psoriasis, is a rare but severe form of psoriasis. gpp is a multi-system disease, consisting of the sudden onset of sterile pustules and erythema often accompanied by fever, malaise, erythroderma, asthenia, myalgia, and arthralgia. life-threatening complications include sepsis, renal failure, neutrophilic cholangitis resulting in hepatic failure, respiratory distress secondary to neutrophilic pneumonitis, congestive heart failure, and death.3 lab abnormalities include an elevated c-reactive protein level, hypocalcemia, hyperleukocytosis with neutrophilia, and elevated liver function tests.3 epidemiologic studies suggest that gpp is rare in the general population. it typically occurs in patients already diagnosed with chronic plaque psoriasis, though it can be the initial presentation of psoriasis as in our patient..4 moreover, gpp is exceedingly rare in children. a review of 1,262 pediatric psoriasis patients found that gpp accounted for only 0.6% of cases.1 known triggers of gpp include hypocalcemia, rapid steroid tapers, pregnancy, and infections.5 one study suggested that upper respiratory infection was the most commonly implicated trigger for gpp.6 of note, our patient reported a recent history of gastroenteritis, which may have been his trigger.. medications associated with gpp flares include minocycline, terbinafine, acetazolamide, hydroxychloroquine, acetazolamide, and salicylates.4 the pathogenesis of pustular psoriasis is not fully known, yet advances in genetics have elucidated the role of three genes in its development. an autosomal recessive pattern mutation in the il-36 receptor antagonist, located on chromosome 2q13q14 was associated with gpp. it is speculated that such a mutation may lead to unregulated secretion of pro-inflammatory cytokines including il-1 and nf-κb.7 a de novo gain of function mutation in the caspase card-14 gene was also identified in a case of childhood gpp.8 this mutation is hypothesized to activate nf-kb and subsequently increase production of the proinflammatory cytokines il-8 and il-36. of note, patients with the card-14 mutation tend to have a severe form of disease that is often refractory to treatment.8 histologically, pustular psoriasis is characterized by neutrophils migrating from the papillary capillaries into the stratum corneum of the epidermis. aggregates of neutrophils, called spongiform pustules of kogoj, accumulate between degenerated and flattened keratinocytes in the upper malpighian layer of the epidermis to form subcorneal macropustules.9 the most important differential diagnosis is acute generalized exanthematous pustulosis (agep). great care must be taken to distinguish the two as management differs. agep typically presents as acute, nonfollicular pustules on an erythematous base, often after ingestion of a new medication, usually antibiotics. key clinical differences between agep and gpp include shorter duration of fever and pustules in agep (9.4 ± 4.6 days in agep compared to 37 ± 20 days) and spontaneous resolution of symptoms for agep but not gpp.10 histologically, gpp can be distinguished from agep by relative lack of eosinophils and necrotic keratinocytes, and presence of tortuous or dilated blood vessels.9 treatment of gpp in the pediatric population is not well studied. based on case reports, acute gpp has been safely treated with discussion skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 451 systemic therapies such as methotrexate, oral retinoids, and phototherapy.2 acitretin is often used as the first-line therapy for longterm management, though care must be taken when using this medication in adolescent females due to teratogenicity. few case reports, including the current one, describe use of low-dose cyclosporine to treat acute gpp in children.11 biologics such as etanercept, adalimumab, and infliximab have been shown to induce remission safely in children as well.12 in summary, we report the case of pediatric patient safely treated with cyclosporine for gpp. given the rarity of gpp in the pediatric population, large cohort studies are necessary to establish best practices in histological diagnosis of gpp compared to other clinically similar lesions, while also establishing treatment safety and efficacy in this particular patient population. conflict of interest disclosures: none funding: none corresponding author: lauren geller, md 5 e 98th street, 5th floor new york ny 10029 tel: (212) 241-9728 fax: (212) 987-1197 email: lgeller.md@gmail.com references: 1. morris a, rogers m, fischer g, williams k. childhood psoriasis: a clinical review of 1262 cases. pediatric dermatology. 2001;18(3):188198. 2. de oliveira st, maragno l, arnone m, fonseca takahashi md, romiti r. generalized pustular psoriasis in childhood. pediatric dermatology. 2010;27(4):349-354. 3. borges-costa j, silva r, goncalves l, filipe p, soares de almeida l, marques gomes m. clinical and laboratory features in acute generalized pustular psoriasis: a retrospective study of 34 patients. american journal of clinical dermatology. 2011;12(4):271-276. 4. william d. james md tbm, dirk elston md. andrews' diseases of the skin: clinical dermatology. 11 ed: saunders; 2011. 5. elston ge, charles-holmes r, carr ra. precipitation of generalized pustular psoriasis by prednisolone. clinical and experimental dermatology. 2006;31(1):133-134. 6. popadic s, nikolic m. pustular psoriasis in childhood and adolescence: a 20-year singlecenter experience. pediatric dermatology. 2014;31(5):575-579. 7. marrakchi s, guigue p, renshaw br, et al. interleukin-36-receptor antagonist deficiency and generalized pustular psoriasis. the new england journal of medicine. 2011;365(7):620-628. 8. jordan ct, cao l, roberson ed, et al. rare and common variants in card14, encoding an epidermal regulator of nf-kappab, in psoriasis. american journal of human genetics. 2012;90(5):796-808. 9. kardaun sh, kuiper h, fidler v, jonkman mf. the histopathological spectrum of acute generalized exanthematous pustulosis (agep) and its differentiation from generalized pustular psoriasis. journal of cutaneous pathology. 2010;37(12):1220-1229. 10. jean l bolognia jlj, and julie v schaffer. dermatology. 3rd ed: elsiever; 2012:135-156. 11. kilic ss, hacimustafaoglu m, celebi s, karadeniz a, ildirim i. low dose cyclosporin a treatment in generalized pustular psoriasis. pediatric dermatology. 2001;18(3):246-248. 12. saikaly sk, mattes m. biologics and pediatric generalized pustular psoriasis: an emerging therapeutic trend. cureus. 2016;8(6):e652. conclusion mailto:lgeller.md@gmail.com skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 608 brief article malignant melanoma within a giant congenital melanocytic nevus in a pediatric patient jackson green, bs4, jessica nye, bs4, kelly turner, pa3,4, matthew r. greives, md3,4, kate mowrey, ms, cgc1,4, adelaide a. hebert, md1,2,4, autumn atkinson, md1,4 1department of pediatrics, university of texas health science center at houston, houston, tx 2department of dermatology, university of texas health science center at houston, houston, tx 3department of plastic surgery, university of texas health science center at houston, houston, tx 4university of texas mcgovern medical school at houston, houston, tx congenital melanocytic nevi (cmn) pose a constellation of challenges that include cosmetic and functional disfigurement, reduction in self-esteem, and the potential to develop into malignant melanoma.1, 2 giant cmns are defined by pigmented proliferations that are greater than 20 cm2 in diameter, and these occur in 1 in 20,000 births, most commonly on the trunk, upper extremities and head and neck regions.2, 3 cmns can change in size and appearance with age from a flat brown plaque to a pigmented and hairy plaque with erosions, ulcerations, or a thickened verrucous surface.4 while all cmns have the potential to transform into malignant melanoma, the highest risk of malignant transformation resides in giant congenital melanocytic nevi with reports of this transformation being as high as 14%.1-5 regular dermatologic screenings by pediatricians are vital to assess changes in giant congenital nevi over time.4 early biopsy and possible surgical intervention can help identify early transformation and potentially reduce the sequelae of melanoma.4 a male infant was born at 39 weeks and 6 days gestation to a 23-year-old primigravida mother who obtained appropriate prenatal care throughout the pregnancy. at the time of birth, the newborn was noted to have a large black plaque with tufts of hair from the scalp to mid-back with numerous smaller satellite lesions on the face, trunk, and extremities. the patient received an mri at 2 days of age to rule out neurocutaneous melanosis. the patient was evaluated in the vascular abstract while giant congenital melanocytic nevi are rare lesions in the pediatric population, malignant transformation within these lesions remains even more rare. a 22-month-old male patient developed a 6.5 mm clark’s level iv melanoma within a giant congenital nevus with an activating nras variant. the need for frequent surveillance and screening of giant congenital melanocytic nevi is essential to identify early signs of melanoma, even in the pediatric population. introduction case report skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 609 anomalies clinic at uthealth mcgovern medical school at 1 month of age and diagnosed with a multifocal congenital melanocytic nevus, congenital ear deformity and positional plagiocephaly (figure 1). the patient was to be followed in our outpatient clinic every six months to screen for possible foci of transformation within the giant congenital nevus. due to the covid-19 pandemic, the patient was delayed in returning to clinic initially. figure 1. large multifocal congenital pigmented nevus at 2 months of age. the patient had his first follow up evaluation at 8 months of age, and an area of the nevus in the preauricular space was biopsied due to concern for a rapid change in texture and thickness. the results of the biopsy were normal. a secondary biopsy was performed at 11 months of age due to a new scalp growth, which was found to be a pyogenic granuloma and was excised with normal pathologic findings. at the 16 month follow up, three new lesions of concern were biopsied, and wide excision was performed due to highly proliferative margins and atypical cells. at the 22 month follow up, a previous lesion showed abnormal coloration and borders, and there was found to be an enlarged posterior cervical lymph node raising concern for possible metastasis (figure 2). figure 2. swelling of posterior cervical lymph nodes at 22 months of age after initiation of nivolumab and ipilimumab. as a part of an oncology work-up, a multiplanar, multisequence mri was performed with and without iv contrast showing a new enlarging posterior cervical lymph node prompting concern for malignant transformation or metastatic disease. skin biopsy showed an invasive, nodular, clark level iv, and breslow thickness 6.5 mm melanoma with mitotic figures and ulceration. the patient had a next generation sequencing analysis that demonstrated an skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 610 nras variant. a repeat multiplanar, multisequence mri of the abdomen and pelvis was performed to evaluate for metastases. results of the mri showed metastases to the bones of the legs and the patient was referred to md anderson to initiate therapeutic intervention with ipilimumab and nivolumab. a pet scan demonstrated enlarging left cervical lymph nodes with central necrosis and increase tracer uptake in t3 vertebra and the intertrochanteric region of the right femur suspicious for bony metastases (figure 3). figure 3. pet scan at 22 months of age exhibiting enlargement of the left cervical lymph nodes with central necrosis, likely metastatic in nature. melanoma represents the deadliest form of skin cancer and the fifth most common cancer by incidence across all races in the united states.6 a 35-year review of pediatric patients found that 2.5 per one million children are diagnosed with melanoma, exhibiting an exceptionally rare occurrence.7 of these children, only 22% are diagnosed with melanoma before puberty.7 preadolescent patients are more likely to present with melanoma on the head and neck and are more likely to be non-caucasian, as in this case.8 early detection and treatment are vital for survival, as prognosis is directly correlated with disease staging.4 when evaluating pediatric nevi, cmns require a unique algorithm of care because their natural history varies from acquired pediatric nevi. acquired melanocytic nevi (amn) are ubiquitous in children, typically appearing in early childhood and increasing in size and number. however, amns only account for 1% of all melanomas in patients younger than 20 years and have a lifetime risk of transformation into melanoma of 1 in 10,000.9 studies indicate the risk of melanoma ranges from 6-14% in giant congenital nevi, while other smaller congenital nevi only have a 1.4% incidence of melanoma.1,3 immunohistochemical and somatic genetic testing may be necessary for diagnosis in unique or recurrent cases of melanoma.3 thus far, the proto-oncogenes, nras and braf, have been identified in approximately 95% and 5-10% in giant cmns, respectively.5 as a pediatrician, it is vital to recognize early indications of transformation to melanoma to provide better outcomes for patients. this case stresses the importance of early detection, serial evaluation, and prompt treatment of melanoma in a giant congenital melanocytic nevus. giant cmns are particularly difficult to manage due to the diagnostic challenge, operative treatment required, and lifelong follow-up and management. a multidisciplinary team encompassing pediatrics, dermatology, plastic surgery, and genetics – as seen in discussion conclusion skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 611 many vascular anomalies centers – is uniquely positioned to play an especially important role in managing this subset of patients and provide timely quality care for these rare and deadly conditions. consent: the parents have provided written consent for the use of the patient’s photos conflict of interest disclosures: none funding: none corresponding author: autumn atkinson, md, faap the university of texas health science center at houston 6341 fannin st, suite jjl 495 houston, tx 77030 references: 1. ehud a, zuker rm. the shifting paradigm in the management of giant congenital melanocytic nevi. plastic and reconstructive surgery. 2014;133(5):1312. doi:10.1097/prs.0000000000000342. 2. gosain ak, santoro td, larson dl, gingrass rp. giant congenital nevi: a 20-year experience and an algorithm for their management. plastic and reconstructive surgery. 2001;108(3):632636. doi:10.1097/00006534-200109010-00005. 3. belysheva ts, vishnevskaya yv, nasedkina tv, et al. melanoma arising in a giant congenital melanocytic nevus: two case reports. diagnostic pathology. 2019;14(1). doi:10.1186/s13000-0190797-1. 4. arneja js, gosain ak. giant congenital melanocytic nevi. plastic and reconstructive surgery. 2009;124(supplement). doi:10.1097/prs.0b013e3181ab11be. 5. lalor l, busam k, shah k. prepubertal melanoma arising within a medium-sized congenital melanocytic nevus. pediatric dermatology. 2016;33(6). doi:10.1111/pde.12961. 6. howlader n, noone am, krapcho m, et al., eds. seer cancer statistics review, 1975-2018. seer. https://seer.cancer.gov/csr/1975_2018/. 7. dean ph, bucevska m, strahlendorf c, verchere c. pediatric melanoma. plastic and reconstructive surgery global open. 2017;5(3). doi:10.1097/gox.0000000000001252. 8. austin mt, xing y, hayes-jordan aa, lally kp, cormier jn. melanoma incidence rises for children and adolescents: an epidemiologic review of pediatric melanoma in the united states. journal of pediatric surgery. 2013;48(11):2207-2213. doi:10.1016/j.jpedsurg.2013.06.002. 9. levy r, lara-corrales i. melanocytic nevi in children: a review. pediatric annals. 2016;45(8). doi:10.3928/19382359-20160720-07. second intention healing for mohs defects of specific anatomic locations of the lower extremities: identifying indications and mitigating challenges kunal malik md,1 tracy ngo bs,2 parth patel md,1 amor khachemoune md, faad, facms2 conclusions 1. sih should be considered as a simple, affordable, and equivalent if not superior alternative to surgical repair for patients without comorbidities that significantly delay or impair wound healing 2. sih is a good option for surgical defects on the leg due to its utility in high visibility areas with active infection and excessive tension; resulting wound contraction allows for a smaller scar with preserved skin tone, contour, and function. 3. w ound healing on the foot can be difficult due to constant sheer forces and high pressure, but sih on the feet can allow for earlier mobilization since the granulation tissue acts as a cushion for ambulation. 4. given the lack of robust studies, randomized control trials and comparative studies with large sample sizes should be conducted to better characterize properties, indications, and challenges of sih on all parts of the lower extremity. clinical relevance sih is potentially underutilized on the lower extremity, which is often viewed as a challenging wound healing location due to unfavorable tissue properties and increased complication risk. however, significant regional tissue variability exists in the lower extremity, and defects left to heal by sih can have similar if not superior functional and cosmetic outcomes in certain situations. 1. dept. of dermatology, icahn school of medicine at mount sinai, new york, ny; 2. division of dermatology, dept. of medicine, albert einstein college of medicine, bronx, ny; 3. dept. of dermatology, suny downstate medical center the authors report no relevant financial disclosures 50 unique articles describing mms of lower extremity cancers and secondary intention healing were found (fig. 1). these included case report/series/report and review (26, 52%), chart reviews (10, 20%), cohort studies (5, 10%), clinical trials (4, 8%), reviews (2, 4%), surveys (1, 2%), statistical analyses (1, 2%), and cross-sectional study (1, 2%). w e covered 15 unique malignancies (adenosquamous carcinoma, atypical intraepidermal, melanocytic proliferation, basal cell carcinoma, bowen's disease, dermatofibrosarcoma protuberans, eccrine porocarcinoma, leiomyosarcoma, malignant adnexal tumors, malignant granular cell tumor, melanoma all subtypes, nonhodgkin's lymphoma, squamous cell carcinoma, subungual epidermoid carcinoma, superficial malignant nerve sheath tumor, verrucous carcinoma, treated with mms in locations from upper leg to the plantar foot figure 1. prisma flow diagram of literature search and study selection results prior to the development of mohs micrographic surgery (mms), surgical defects were often closed with sutures due to the general conception that primary closure produced superior cosmesis versus secondary intention healing (sih). the terms “leg” and “lower leg” are used uniformly to reference the anatomic area from just below-the-knee to the malleoli whereas “lower extremity” references the entire anatomic area from below-the-knees to the toes. healing of lower extremity defects is often viewed as challenging due to unfavorable tissue properties and increased risk of complications, however significant regional tissue variability in this area warrants further exploration. furthermore, wound characteristics and outcomes of sih for mms defects of specific lower extremity sites is not well described in the literature.1,2 to address possible underutilization of sih on the lower extremity, site-specific indications and challenges of sih below-the-knee need exploration. a systematic review of the literature from inception of databases to january 2, 2021 using pubmed, embase, and cochrane library using search terms: 1) mohs surgery and lower extremity, leg, foot and 2) mohs and lower extremity, leg, foot was performed. abstracts were screened for articles pertaining to mms of lower extremity cancers and secondary intention healing. this review was conducted in concordance with the preferred reporting items for systematic reviews and meta-analysis (prisma) guidelines. inclusion and exclusion criteria all articles published in english were included. all other articles were excluded. case reports with unspecified reconstruction/wound healing after mms were excluded. data extraction to screen for relevance, abstracts were perused and those without abstracts underwent full-text review. duplicate articles were identified and removed. articles that met the inclusion criteria were subjected to full-text review. methods background sih on the leg and foot in a retrospective study identifying risk factors for complications after below-the-knee mms, most defects (74%) were healed by sih.3 the complication rate of sih (16%) was favorable compared to flaps and grafts (both 50%), but inferior to primary closure (8%); conclusions were limited by small sample size.3 in a case series of acral melanomas of the feet, most defects were healed by sih (63.6%). this study had a small sample size and did not stratify by treatment modality.4 in a prospective study to determine rates of bleeding and wound healing complications in outpatient dermatologic surgery, only 2.5% were left to heal with sih.5 though this study had a large sample size, it included both mms (1369, 72%) and surgical excision (542, 28%). sih can also produce acceptable cosmetic and functional outcomes in larger, deeper surgical defects.3,6,7 a survey consisting of 293 respondents from acms revealed that mohs surgeons with over 15 years of experience were significantly more likely to elect to heal deeper and larger surgical defects secondarily than surgeons with 5 or less years of experience (p < .05)— suggesting that sih may be underutilized by less experienced surgeons.6 a retrospective study exploring factors associated with surgical site infections of the lower extremity found no difference in infection rate between sih and surgical repair, sih had a lower odds ratio (2.1, 95% confidence interval 0.9 -5.0; p = .1) than complex layered closure (4.5, 95% confidence interval 1.5-13.2; p =.006).8 sih on the foot was also found to have superior clinical, functional, and cosmetic outcomes compared to split-thickness and fullthickness skin grafts without the added initial procedure time and creation of a secondary defect.3,7,9,10 references 1. liu ky et al. ann plast surg 2020;85(s1 suppl 1):s28-s32. 2. mott kj et al. dermatol surg 2003;29(7):712-22. 3. honaker js et al. dermatol surg 2016;42(4):568-70. 4. hutcheson ac et al. dermatol surg 2007;33(1):1-10. 5. bordeaux js et al. j am acad dermatol 2011;65(3):576-583. 6. vedvyas c et al. dermatol surg 2017;43(3):415-423. 7. audrain h et al. dermatol surg 2015;41(4):493-8. 8. nathan nr et al. j am acad dermatol 2020;83(1):274-276. 9. oganesyan g et al. dermatol surg 2013;39(9):1334-9. 10. schoenfeld j et al. dermatol online j 2017;23(2). skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 886 brief article perspectives of vitiligo patients: voices from national vitiligo conferences katie a. o’connell, md, ms1, ronnie m. youssef, md2, angeli eloise torres, md3, richard h. huggins, md3 1 department of medicine, vanderbilt university medical center, nashville, tn 2 texas a&m health science center, college of medicine, bryan, tx 3 photomedicine and photobiology unit, department of dermatology, henry ford health system, detroit, mi vitiligo is a chronic skin condition affecting 0.5 – 2% of the population that may result in psychosocial effects including shame, depression, anxiety, and stigmatization.1 patients with vitiligo report low quality of life (qol) scores, which can be improved with the help of support groups, online communities, and dedicated research associations/societies. wvd is an annual global event which originated in nigeria in 2011. wvd serves as a celebration of the vitiligo community with the goals of raising awareness about the condition and recognizing the hardships faced by individuals with vitiligo. in the united states, the many individual vitiligo support groups have collaborated on a joint national us world vitiligo day (us-wvd) since 2016. abstract in the united states, many individual vitiligo support groups have collaborated on a joint national us world vitiligo day since 2016. as part of the 2020 and 2021 us world vitiligo day virtual events, polls were conducted that solicited information from participants regarding their life with vitiligo. a majority (76% in 2020; 92% in 2021) would like a cure for vitiligo. in 2020 and 2021, 40% and 35% responded they both show and hide their vitiligo when asked how they display their skin. a minority, 14% in 2020 and 5% in 2021, reported their vitiligo treatments were fully covered by their insurance. when polled about acceptance, in 2021, 40% reported they were accepting of their vitiligo most days. in 2021, 20% were interested in trying treatments, even if they included moderate side effects and 29% were interested, if minimal side effects. results herein suggest that while many patients are accepting of their disease, many also want a cure. additionally, dermatologists should advocate for coverage of vitiligo treatment, while also taking insurance coverage into account when discussing treatment options. further, vitiligo patients require individualized care considering some patients may be open to attempting more aggressive treatment, despite the side effect profiles, while others are not interested in treatment or only willing to attempt treatments without side effects. introduction methods skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 887 in both 2020 and 2021, us-wvd was held virtually, co-hosted by the global vitiligo foundation and myhealthteams, a social network platform for patients with chronic conditions.2 in total, 355 live viewers from 28 countries attended the 2020 us-wvd and 385 viewers from 27 countries attended the 2021 event. participants during each event were surveyed about their vitiligo via live polling through the zoom platform. questions were asked at various timepoints throughout the programming of each event and were open for anonymous response from all live attendees. thus, all live attendees were included and those who were not currently at their viewing device or watching a recording of the event were excluded. survey questions were developed by a panel of dermatologists with a specific interest in vitiligo in conjunction with myhealthteams representatives specifically for use during virtual wvd. five questions were asked in 2020 and seven questions were asked in 2021. when asked, “do you want a cure for vitiligo?” 76% and 92% of respondents said they wanted a cure, while 24% and 8% said they did not in 2020 (n=70) and 2021 (n=39), respectively (table 1). when asked whether they wanted to show off their vitiligo or hide it, 44% and 57% responded saying they show it off, 16% and 8% saying they hide it, and 40% and 35% saying they both show and hide it in 2020 (n=45) and 2021 (n=37), respectively. when asked if vitiligo treatments were covered by their insurance, 14% and 5% noted all were covered, 46% and 46% noted some were covered and 40% and 49% noted no treatments were covered in 2020 (n=50) and 2021 (n=37), respectively. in 2021, when asked how they feel about their vitiligo (n=87), 45% responded fully accepting most days, 40% accepting some days, 8% not accepting most days, and 7% not accepting at all. in 2021, when asked if they were interested in trying treatments for vitiligo (n=82), 23% said yes, if no side effects, 29% replied yes, even if minimal side effects, 20% replied yes, even if moderate side effects, 14% responded no and 13% were not sure. two questions regarding age and sunscreen usage are excluded from this report. an overwhelming majority (76-92%) would like a cure for vitiligo and almost half are willing to try treatments with known side effects. taken together, these underscore the profound impact vitiligo can have on patients’ qol. unfortunately, at this time there is only one food and drug administration approved treatment for repigmentation of vitiligo lesions, ruxolitinib cream, approved in july of 2022.3 we clearly have significant unmet need with regard to treatment options for our vitiligo patient population. from the clinical side, considering the number of patients willing to attempt treatment despite potential side effects, physicians should educate themselves about the oral treatments that have evidence of effectiveness in vitiligo treatment and discuss escalation of therapy from topical to oral treatments for appropriate patients. insurance coverage for vitiligo treatments varies greatly despite robust data showing treatment efficacy in delaying disease progression.5 during the us-wvds only a small number of those surveyed reported full insurance coverage for vitiligo treatment and, from 2020 to 2021 this number dropped even further. lack of access to treatment as a result of insurance coverage and financial barriers potentially further exacerbates health results discussion skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 888 table 1. selected poll results from world vitiligo day 2020 and 2021. *poll question asked at wvd-2021 only questions % responses (total n) do you want a cure for vitiligo? yes no 2020 (n=70) 76 24 2021 (n=39) 92 8 do you show off your vitiligo or hide it? show hide both 2020 (n=45) 44 16 40 2021 (n=37) 57 8 35 are your vitiligo treatments covered by your health insurance? all some none 2020 (n=50) 14 46 40 2021 (n=37) 5 46 49 how do you feel about your vitiligo?* (n=87) fully accepting most days accepting some days not accepting most days not accepting at all 45 40 8 7 are you interested in trying treatments for vitiligo?* (n=82) yes, if no side effects yes, even if minimal side effects yes, even if moderate side effects no not sure 23 29 20 14 13 skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 889 disparities among the pediatric population and those with darker skin phototypes.5 patient advocacy for individuals with vitiligo remains an essential part of caring for these patients. clinicians must help continue the shift in the perception of vitiligo from that of a purely cosmetic condition to a true medical disease, particularly with respect to resistant insurance companies. in the meantime, clinicians should take insurance coverage into consideration when discussing treatment options with their patients. roughly half of surveyed individuals report no qualms about showing their vitiligo off, while the other half prefer to hide their vitiligo at least part of the time. just under half of those surveyed feel fully accepting of their vitiligo most days, while a slight majority report struggling with their disease a significant proportion of the time. this is in line with the clear dichotomy between public/policymaker perceptions of supermodels proudly displaying their vitiligo on social media and individuals who feel uncomfortable in their appearance as a result of their vitiligo.6 similarly, contrasting schools of thought exist within the vitiligo support community between those who advocate for a cure versus those who promote acceptance of the condition. it is useful for clinicians to take into consideration both viewpoints, as patients who belong to the latter may not be receptive to an aggressive treatment approach that would likely be more appealing to the former group. ultimately, clinicians should be cognizant that no two vitiligo patients are alike and even the same individual’s feelings towards their disease may change over time. additionally, given that a majority of surveyed individuals hide their vitiligo at least part of the time and 15% of individuals surveyed generally do not feel accepting of their disease, clinicians should make sure to mention camouflaging options to their patients. limitations of this study include small sample size and variable response rates. given that survey questions were asked to all attendees anonymously via live programming, it is possible that responses may have come from individuals not currently living with vitiligo. us-wvd provided an invaluable opportunity for us to learn from our vitiligo patients. they reminded us that, while many patients are accepting of their disease, many patients also want a cure. when encountering a vitiligo patient whose disease is progressing despite topical therapy, providers should individualize care and bear in mind that some patients may be open to attempting oral therapy despite the side effect profiles. additionally, providers should advocate for coverage of vitiligo treatment, while also taking insurance coverage into account when discussing treatment options. by paying attention to what vitiligo patients are telling us, we can better partner with them to help them achieve their individual and collective therapeutic goal. conflict of interest disclosures: kao, rmy, and aet have no relevant disclosures. rhh is an investigator for pfizer, incyte, arcutis and the immune tolerance network. funding: none corresponding author: richard h. huggins, md department of dermatology, henry ford medical center – new center one, 3031 west grand boulevard, suite 800, detroit, michigan 48202 phone: (800) 436-7936 email: rhuggin1@hfhs.org references: 1. ezzedine k, eleftheriadou v, whitton m, van geel n. vitiligo. lancet. 2015 jul 4;386(9988):74-84. doi: 10.1016/s0140conclusion mailto:rhuggin1@hfhs.org mailto:rhuggin1@hfhs.org skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 890 6736(14)60763-7. epub 2015 jan 15. pmid: 25596811. 2. my health teams. my vitiligo team [internet]. cited 2022 february 1. available from: https://www.myvitiligoteam.com 3. us food and drug administration. fda approves topical treatment addressing repigmentation in vitiligo in patients aged 12 and older [internet]. 2022 july 19 [cited 2022 september 15]. available from: https://www.fda.gov/drugs/news-eventshuman-drugs/fda-approves-topical-treatmentaddressing-repigmentation-vitiligo-patientsaged-12-and-older 4. searle t, al-niaimi f, ali fr. vitiligo: an update on systemic treatments. clin exp dermatol. 2021 mar;46(2):248-258. doi: 10.1111/ced.14435. epub 2020 dec 22. pmid: 33350506. 5. blundell a, sachar m, gabel ck, bercovitch lg. the scope of health insurance coverage of vitiligo treatments in the united states: implications for health care outcomes and disparities in children of color. pediatr dermatol. 2021 nov;38 suppl 2:79-85. doi: 10.1111/pde.14714. epub 2021 jul 16. pmid: 34272764. 6. harris j. vitiligo gets even more visibility: chantelle brown-young on america’s next top model [internet]. 2014 august 6 [cited 2022 march 10]. available from: https://www.umassmed.edu/es/vitiligo/blog/bl og-posts1/2014/08/vitiligo-gets-even-morevisibility-chantelle-brown-young-on-americasnext-top-model/ https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-topical-treatment-addressing-repigmentation-vitiligo-patients-aged-12-and-older https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-topical-treatment-addressing-repigmentation-vitiligo-patients-aged-12-and-older https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-topical-treatment-addressing-repigmentation-vitiligo-patients-aged-12-and-older https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-topical-treatment-addressing-repigmentation-vitiligo-patients-aged-12-and-older skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 542 brief article aquagenic urticaria in an adolescent following covid-19 vaccination john t. broderick, bs1, thomas d. selby, md1, julian trevino, md1 1department of dermatology, wright state university boonshoft school of medicine, fairborn, oh over 600 million doses of the covi9-19 vaccine have been administered in the united states.1 close to 96% of doses administered have been mrna vaccines from pfizer-biontech and moderna.1 these safe and effective vaccines have been associated with cutaneous reactions in a subset of patients. the most common cutaneous reactions are delayed injection site reactions involving redness, swelling, pain, or induration that occur within 7 days following vaccination.2,3 most reactions are self-limiting and do not require treatment. more rare vaccine reactions include urticaria, morbilliform eruptions, pityriasis rosea, and vasculitis.2,3 in one large review of 40,640 patients who received mrna vaccines, urticaria involving itchy wheels occurred in 0.3% of patients after the first vaccine dose and in 0.6% of patients after the booster.4 most urticarial reactions have been delayed hypersensitivity reactions, occurring at least 4 hours after injection, and have been symptomatically managed with antihistamines.5 chronic spontaneous urticaria lasting >6 weeks has been reported but these reactions were not associated with specific exacerbating factors.6,7 aquagenic urticaria (au) is a unique type of urticaria caused by skin contact with water. we present the first reported case of aquagenic urticaria induced by the covid-19 vaccine from our review of the available literature. a 12-year-old african american male with a history of atopic dermatitis and herpes labialis received the first dose of the pfizerbiontech covid-19 vaccine on aug 3, 2021 abstract a subset of patients receiving covid-19 vaccinations develops cutaneous reactions. the majority are delayed hypersensitivity reactions that resolve spontaneously without treatment. more rarely, cutaneous manifestations such as urticaria, vasculitis, and morbilliform eruptions have been reported. aquagenic urticaria is a form of chronic inducible urticaria caused by skin contact with water. characteristic 1-2mm folliculopapular urticarial papules appear 20-30 minutes following water exposure and spontaneously resolve within 30-60 minutes of water removal. a water provocation test is the gold standard of diagnosis. the mainstay of treatment is 2nd generation h1 antihistamines taken before water exposure. we report the development of aquagenic urticaria in a 12-year-old african american male patient after receiving the pfizer-biontech mrna covid-19 vaccine. introduction case report skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 543 and developed shortness of breath and throat swelling requiring epipen administration and hospital monitoring. the following week, the patient started developing hives on his trunk, arms, legs, and face after showering, regardless of water temperature. the hives started minutes after showers and resolved within 20-60 minutes. the patient endorsed pruritis and discomfort but denied wheezing, shortness of breath, throat or lip swelling, and vomiting. a water challenge test was positive with small erythematous to violaceous papules consistent with urticaria in his fitzpatrick type v skin were noted in the test area with the patient reporting subjective symptoms of burning and pruritis (figure 1). dermatographism was negative. figure 1. water provocation test performed according to expert consensus.8 a) a towel was soaked in room temperature water and placed on the left posterior shoulder for 20 minutes. b) 1-2mm erythematous papules (black arrows) were noted in the test area with the patient reporting symptoms of burning and pruritis. on follow-up, the patient reported a decreased duration of the hives on 20mg bid of cetirizine but the urticaria persisted following showers. narrow-band uvb phototherapy was trialed, but the patient was unable to tolerate due to post-treatment migraine. other treatment options including: dupilumab, omalizumab, and β-alanine supplementation were discussed but further treatment was deferred at that time. at 10 months post-vaccination, the patient reported marked improvement. the hives were occurring sporadically and in fewer numbers. aquagenic urticaria is a rare dermatologic reaction that involves development of hives following exposure to water. chronic inducible urticaria is the consistent development of hives following exposure to triggers including cold, sunlight, sweat, and water.8 au has a 1-2 mm folliculopapular urticarial appearance that is very similar to the pattern seen in cholinergic urticaria.3 wheals are commonly seen on the trunk and upper extremities 20-30 minutes following exposure to water and spontaneously resolve within 30-60 minutes after water removal.9 au occurs regardless of water temperature and ph.8 interestingly, au is often localized to certain areas of the body even when there is whole body contact with water.10 the condition causes pruritus and rarely has associated symptoms of headache, wheezing and shortness of breath, and angioedema.9,10 the diagnosis can usually be made from patient history, but it can be difficult to delineate between cholinergic urticaria if the hives occur following sweating. the gold standard diagnostic test is a water provocation test.8 the mechanism of au is thought to be related to mast cell degranulation and release of histamine.9 thus, the mainstay of treatment is with 2nd generation h1 antihistamines taken before water exposure.9,10 greater treatment success has been achieved using antihistamine doses up to 4 times of standard dosing.10 for symptoms refractory to antihistamines, other options to consider are barrier creams, omalizumab, dupilumab, and uv light therapy.9 discussion skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 544 the reported cutaneous reactions for covid-19 are similar to those reported in other vaccines.3 polyethylene glycol (peg) and polysorbate 80 are components that have been identified as possible allergic triggers in other vaccines.3 peg is present in both pfizer and moderna; polysorbate 80 is a component of the oxford/astrazeneca and johnson & johnson vaccines. of note, the patient’s symptoms started to resolve around 10 months post-vaccination. it has been shown that covid-19 antibodies induced by disease and vaccination decrease over time.11 the improvement of our patient ’s symptoms could be correlated with waning antibodies generated from the initial vaccination. cutaneous reactions to covid19 mrna booster vaccinations have been reported, including reactions in patients that did not have cutaneous reactions to primary vaccine doses.12 we predict similar symptoms in response to a booster vaccination because of activation of memory b cells and production of antibodies. we recommended against a booster dose in our patient due to prior anaphylactic reaction. dermatologists serve an important role in identifying new adverse cutaneous reactions as mass vaccination efforts with booster vaccines continues. they can accurately interpret skin reactions and provide guidance regarding further vaccination. a standardized grading scale for covid-19 vaccineassociated cutaneous reactions was recently proposed and utilizes the fda’s toxicity grading scale for local reactions and the nci’s common terminology criteria for adverse events (ctcae) for generalized reactions.13 most occurrences are acute selfresolving local injection site reactions, and these patients should be encouraged to continue to receive booster doses per cdc recommendations. chronic dermatologic manifestations should be treated according to the standard of care, and symptoms may improve as vaccine-induced immunity wanes over time. current cdc guidelines recommend referral to an allergist if a patient has a vaccine reaction within 4 hours of administration or severe symptoms.14 patients with a suspected ige-mediated immediate hypersensitivity reaction may benefit from skin testing using peg or polysorbate to help guide future vaccination decisions.15 patients with delayed hypersensitivity reactions should consult with an allergist to discuss risk/benefits of future doses but there are no current guidelines recommending for or against receiving booster doses.15 we present the first reported case of aquagenic urticaria following covid-19 vaccination in a skin of color patient and propose a possible mechanism for waning symptoms. there were no other associated medications or illnesses to explain the onset of symptoms. this case demonstrates a new adverse event that should be included in vaccine monitoring. conflict of interest disclosures: none funding: none corresponding author: john broderick, bs 3648 lilac ln unit 3 beavercreek, oh 45431 phone: (513) 635-2490 email: broderick.18@wright.edu references: 1. cdc. covid data tracker. centers for disease control and prevention. published march 28, 2020. accessed july 31, 2022. https://covid.cdc.gov/covid-data-tracker 2. qaderi k, golezar mh, mardani a, et al. cutaneous adverse reactions of covid‐19 vaccines: a systematic review. dermatol conclusion skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 545 ther. 2022;35(5):e15391. doi:10.1111/dth.15391 3. bellinato f, maurelli m, gisondi p, girolomoni g. cutaneous adverse reactions associated with sars-cov-2 vaccines. j clin med. 2021;10(22):5344. doi:10.3390/jcm10225344 4. robinson lb, fu x, hashimoto d, et al. incidence of cutaneous reactions after messenger rna covid-19 vaccines. jama dermatol. 2021;157(8):1000-1002. doi:10.1001/jamadermatol.2021.2114 5. mcmahon de, amerson e, rosenbach m, et al. cutaneous reactions reported after moderna and pfizer covid-19 vaccination: a registry-based study of 414 cases. j am acad dermatol. 2021;85(1):46-55. doi:10.1016/j.jaad.2021.03.092 6. thomas j, thomas g, chatim a, shukla p, mardiney m. chronic spontaneous urticaria after covid-19 vaccine. cureus. 13(9):e18102. doi:10.7759/cureus.18102 7. alflen c, birch k, shilian r, wu ss, hostoffer r. two cases of well controlled chronic spontaneous urticaria triggered by the moderna covid-19 vaccine. allergy rhinol (providence). 2021;12:21526567211026270. doi:10.1177/21526567211026271 8. magerl m, altrichter s, borzova e, et al. the definition, diagnostic testing, and management of chronic inducible urticarias – the eaaci/ga2len/edf/unev consensus recommendations 2016 update and revision. allergy. 2016;71(6):780-802. doi:10.1111/all.12884 9. wassef c, laureano a, schwartz ra. aquagenic urticaria: a perplexing physical phenomenon. acta dermatovenerologica croatica. 2017;25(3):234-237. 10. rujitharanawong c, kulthanan k, tuchinda p, chularojanamontri l, metz m, maurer m. a systematic review of aquagenic urticariasubgroups and treatment options. j allergy clin immunol pract. published online may 6, 2022:s2213-2198(22)00477-9. doi:10.1016/j.jaip.2022.04.033 11. hamady a, lee j, loboda za. waning antibody responses in covid-19: what can we learn from the analysis of other coronaviruses? infection. 2022;50(1):11-25. doi:10.1007/s15010-021-01664-z 12. prasad s, mcmahon de, tyagi a, et al. cutaneous reactions following booster dose administration of covid-19 mrna vaccine: a first look from the american academy of dermatology/international league of dermatologic societies registry. jaad international. 2022;8:49-51. doi:10.1016/j.jdin.2022.04.004 13. singh r, ali r, prasad s, chen st, blumenthal k, freeman ee. proposing a standardized assessment of covid-19 vaccine-associated cutaneous reactions. journal of the american academy of dermatology. published online may 13, 2022. doi:10.1016/j.jaad.2022.05.011 14. anvari s, samarakoon u, fu x, et al. urticaria and/or angioedema secondary to mrna covid-19 vaccines: updates from a united states case registry. allergy. doi:10.1111/all.15447 15. banerji a, wickner pg, saff r, et al. mrna vaccines to prevent covid-19 disease and reported allergic reactions: current evidence and suggested approach. the journal of allergy and clinical immunology: in practice. 2021;9(4):1423-1437. doi:10.1016/j.jaip.2020.12.047 skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 421 brief article vismodegib as a treatment for multiple non-locally advanced basal cell carcinomas robert frantz, md1, mitchell herold, md2, clara curiel-lewandrowski, md2 1 university of florida college of medicine, gainesville, fl 2 university of arizona college of medicine, division of dermatology, tucson, az bcc is the most common cutaneous malignancy with an increasing incidence rate since 1990.1 localized therapies are useful when disease involvement is minimal, multifocal, or in cosmetically sensitive areas which make surgical excision less feasible.2 for metastatic or locally advanced bcc, frequently associated with significant morbidity, the hedgehog pathway inhibitor vismodegib is an fda approved and effective alternative.3 occasionally, patients may present with multiple small bccs simultaneously which are so numerous that excision and repair may be undesirable. the use of vismodegib to treat non-locally advanced bcc has also been reported, although in conjunction with adjuvant imiquimod 5% cream.4 vismodegib is taken once daily until clinical resolution of disease or intolerable side effects are reached, after which a pulse dose method of treatment has been suggested, however data and fda approval regarding an intermittent administration schedule is lacking.3 adverse effects are expected during treatment, with muscle spasms, alopecia, and dysgeusia being most common.5 we report the case of a 77-year-old female who presented with a stage iib melanoma of the right cheek and seven pearly pink papules and plaques (fig. 1) highly consistent with superficial and nodular bccs. due to physical and emotional exhaustion following treatment of the right cheek melanoma, the patient opted against any further invasive procedures. topical therapies were offered, however the nodular component of some of the lesions raised concerns of effectiveness and the multifocal nature raised issues regarding effective patient compliance. radiation was discussed but considered an unattractive option given the numerous sites, repeated sessions, and her overall excellent health. vismodegib was presented as an off-label option for potentially decreasing the size and number of lesions, and the patient started abstract we present the case of a 77-year-old female with seven non-locally advanced basal cell carcinomas (bccs) of the face who achieved a clinical complete response (cr) in six lesions after completing twelve months of vismodegib monotherapy with tolerable side effects. this case investigates the offlabel practical use of vismodegib monotherapy to treat multiple non-locally advanced bccs and reduce the surgical burden of disease in select patients. introduction case report skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 422 150 mg daily. she tolerated the medication well, noting minor eyebrow alopecia and occasional muscle cramps, neither of which were dose limiting. after nine months of therapy, the patient showed clinical resolution of all facial lesions (fig. 2) and was switched to a pulse dose regimen (one month off, two months on) to maximize the durability of her response. at twelve months, 6/7 lesions maintained a cr and the vismodegib was stopped, one lesion on the right mandible with a small focus of clinically recurrent disease was treated with imiquimod 5% cream. figure 1. superficial and nodular bccs on the face before treatment. figure 2. resolution of all facial lesions after nine months of therapy with vismodegib. the treatment of multifocal bcc can be difficult for patients. multiple surgeries can be tiresome, especially when extensive reconstructions lead to prolonged recovery times or repeated procedures and wounds. topical therapies minimize this concern, but in some cases, nodular or dispersive tumors raise issues with efficacy or patient adherence. therefore, alternative options to decrease disease burden may be pursued initially. vismodegib appears to be a reasonable alternative, with an objective response rate (orr) of 42.9% at 9-month follow-up and 47.6% after 21 months of treatment.6 as seen in our case, vismodegib may be a viable treatment option for reducing the surgical burden of disease or stabilizing tumors until patients are ready for more definitive therapy. in patients with numerous bccs, even a fraction of lesions obtaining a cr can potentially mitigate procedures while still achieving positive outcomes, assuming side effects are tolerable. while our patient showed a clinical cr in 85.7% of her bccs, no biopsy was performed to confirm histologic clearance, and the potential for future recurrence remains unknown. additionally, counseling of the limitations and side effects of vismodegib should be discussed, including the risk of developing noncontiguous tumor which may reduce the effectiveness of subsequent micrographically controlled surgery of nonresponsive lesions. prospective trials utilizing vismodegib for multiple, non-locally advanced bcc are needed to quantify overall clinical utility and the effect of pulse dosing on durability of response in these patients. conflict of interest disclosures: none funding: none corresponding author: mitchell herold, md division of dermatology university of arizona college of medicine po box 245024 1515 n. campbell ave. tucson, az 85724 discussion skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 423 phone: (520) 694-2020 email: mitchherold@arizona.edu references: 1. aggarwal p, knabel p, fleischer jr a. united states burden of melanoma and nonmelanoma skin cancer from 1990 to 2019. am acad dermatol. 2021 aug;85(2):388-395. 2. lanoue j, goldenberg g. basal cell carcinoma: a comprehensive review of existing and emerging nonsurgical therapies. j clin aesthet dermatol. may 2016;9(5):26-36. 3. tronconi mc, solferino a, giordano l, borroni r, mancini l, santoro a. tailored toxicity-driven administration of vismodegib in patients with multiple or locally advanced basal cell carcinoma: a pilot analysis. front oncol. 2020;10:563404. 4. markowitz o, schwartz m. the use of noninvasive optical coherence tomography to monitor the treatment progress of vismodegib and imiquimod 5% cream in a transplant patient with advanced basal cell carcinoma of the nose. j clin aesthet dermatol. aug 2016;9(8):37-41. 5. sofen h, gross kg, goldberg lh, et al. a phase ii, multicenter, open-label, 3-cohort trial evaluating the efficacy and safety of vismodegib in operable basal cell carcinoma. j am acad dermatol. jul 2015;73(1):99105.e101. 6. dummer r, ascierto pa, basset-seguin n, et al. sonidegib and vismodegib in the treatment of patients with locally advanced basal cell carcinoma: a joint expert opinion. j eur acad dermatol venereol. sep 2020;34(9):1944-1956. skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 531 brief article a case of pseudoverrucous papules and nodules in an adult with spinal dysraphism gregory ugoh, bs1, caroline crain, md2, brandon goodwin, md2 1 john sealy school of medicine, galveston, tx 2 department of dermatology, john sealy school of medicine, galveston, tx pseudoverrucous papules and nodules (ppn), an uncommon entity, occurs as a results of chronic irritant contact dermatitis from repeated exposure to urine and feces. ppn most commonly occurs in infants but has also been reported in adults in association with urostomies, colostomies, chronic urinary incontinence, chronic fecal incontinence, and potentially spinal dysraphism.1 dubowitz syndrome is a rare autosomal recessive disorder characterized by microcephaly, developmental and motoric delay, failure to thrive, abnormal facies, and short stature. less than 200 cases have been reported in literature and life expectancy is often decreased in most cases.5 herein we present a case of perianal ppn in a patient with dubowitz syndrome and spina bifida. a 42-year-old male with a history of dubowitz syndrome and associated spina bifida resulting in chronic urinary and fecal incontinence presented to the dermatology clinic with a perianal rash of an unknown duration. of note, the patient denied any sensory perception in the area due to his spinal dysraphism. on physical exam, a verrucous, macerated plaque with surrounding hyperpigmentation was noted along his inferior sacrum and superior intergluteal cleft (figure 1). the differential diagnosis at this time included condyloma acuminata, verrucous carcinoma, squamous cell carcinoma, and pseudoverrucous papule and nodules (ppn) secondary to chronic irritant contact dermatitis. bacterial and fungal cultures were obtained (both negative) as well as a punch biopsy for histopathology. abstract pseudoverrucous papules and nodules (ppn) occur in the setting of chronic irritant contact dermatitis commonly due to urine or feces. ppn most commonly affects infants but has also been reported in association with urostomies, colostomies, chronic urinary incontinence, encopresis, chronic fecal incontinence, spinal cord injury, and potentially spinal dysraphism. herein, we present the case of a patient with spina bifida in association with dubowitz syndrome who presented with perianal ppn. to our knowledge, there is only one other case reported in the literature of a patient with spina bifida who presented with ppn. introduction case report skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 532 punch biopsy revealed pseudoepitheliomatous verrucous epidermal hyperplasia and underlying dilated vessels with papillary edema. the histopathological findings taken together with the clinical presentation were consistent with ppn. the patient was started on a combination of triamcinolone 0.1% ointment and nystatin 100,000 units/gram twice daily in addition to frequent diaper changes with liberal use of a zinc oxide-containing barrier cream. significant clinical improvement was observed 2 months after initiation of treatment (figure 2). ppn is a rare clinical manifestation of chronic irritant contact dermatitis associated with repeated exposure to urine or feces. it typically presents asmultiple, gray or erythematous, dome-shaped or verrucous papules, plaques, and nodules in genital, perianal, and peristomal sites.1 histopathologically, this condition demonstrates marked psoriasiform epidermal hyperplasia with broad hyperparakeratosis.1 a moist environment and increase in ph secondary to ammonia present in feces and urine increases the permeability of the skin and compromises its natural barrier function. 2 most cases of ppn in the literature are described in children and in patients with ostomies. to our knowledge, there is only one other case in the literature, discussion figure 1. multiple verrucous nodules coalesced to form plaques at the perianal area. figure 2. macerated plaque at the perianal area with minimal overlying crust. skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 533 reported by dandale et al., of ppn in an adolescent patient with spina bifida.1 the mainstay of therapy for ppn focuses on the management of fecal/urinary incontinence and resulting irritant contact dermatitis. if incontinence cannot be corrected, meticulous hygiene practices should be implemented including frequent diaper changes with gentle cleansing and drying of the area followed by liberal use of barrier creams such as petroleum or zinc to protect the skin from irritation by urine and feces. 4 also, vinegar soaks and oral ascorbic acid can be used to acidify the urine and reduce irritation.3 secondary infections are a relatively common complication of ppn and the area should be monitored closely for signs of infection. figure 3. a) 20x low power photomicrograph: pseudoepitheliomatous verrucous epidermal hyperplasia with marked hyperparakeratosis and underlying dilated vessels with papillary dermal edema consistent with pseudoverrucous papules (lymphedema). b)100x high power photomicrograph: acanthotic epidermis with bulbous irregular downgrowths and associated increased ectatic dermal vessels with papillary dermal edema. in conclusion, pseudoverrucous papules and nodules (ppn) is an uncommon condition that can clinically mimic several infectious, inflammatory, and neoplastic processes but should be suspected in cases of chronic irritant contact dermatitis from urine and feces. furthermore, this case demonstrates the rare association between ppn and spinal dysraphism. conflict of interest disclosures: none funding: none corresponding author: gregory ugoh, bs the university of texas medical branch at galveston john sealy school of medicine email: gaugoh@utmb.edu references: 1. dandale a, dhurat r, ghate s. perianal pseudoverrucous papules and nodules. indian j sex transm dis aids. 2013;34(1):44-46. doi:10.4103/0253-7184.112939 2. kamat d, malathi m, prabhakaran n, thappa dm. pseudoverrucous papules and nodules in an infant with penoscrotal hypospadiasis. indian dermatol online j. 2017;8(6):503-505. doi:10.4103/idoj.idoj_410_ 3. lyon cc, smith aj, griffiths ce, beck mh. the spectrum of skin disorders in abdominal stoma patients. br j dermatol. 2000 dec;143(6):124860. doi: 10.1046/j.1365-2133.2000.03896.x. pmid: 11122029. 4. wesner e, vassantachart jm, jacob se. art of prevention: the importance of proper diapering practices. int j womens dermatol. 2019;5(4):233-234. published 2019 mar 3. doi:10.1016/j.ijwd.2019.02.005 5. stewart dr, pemov a, johnston jj, sapp jc, yeager m, he j, boland jf, burdett l, brown c, gatti ra, alter bp, biesecker lg, savage sa. dubowitz syndrome is a complex comprised of multiple, genetically distinct and phenotypically overlapping disorders. plos one. 2014 jun 3;9(6):e98686. doi: 10.1371/journal.pone.0098686. pmid: 24892279; pmcid: pmc4043752. conclusion skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 546 brief article zosteriform lichen planus as a manifestation of wolf’s isotopic response george glinos, md1; madeline j. hooper, ba2; g. eli morey, md, mph1,2; lucia seminariovidal, md phd1,2 1 department of dermatology and cutaneous surgery, university of south florida (usf), tampa, fl 2 department of cutaneous oncology, h. lee moffitt cancer center, tampa, fl wolf’s isotopic response is the occurrence of a new skin disorder at the site of another unrelated and already healed skin disease.1 formally characterized in 1995, wolf’s isotopic response was reported in the literature as early as 1955, when wyburnmason described 26 cases of malignant tumors (i.e., squamous cell carcinoma, basal cell carcinoma, breast carcinomas) arising in areas of previous varicella zoster (vzv) and herpes simplex virus (hsv) infections.2 subsequent studies have confirmed a predilection for epidermal carcinomas to develop in skin previously affected by herpes viruses.3 wolf’s isotopic response has also been noted after dermatophyte infections, mycobacterial infections, erythema multiforme, and even striae distensae.4-6 moreover, this phenomenon has been seen in association with various inflammatory disorders arising months to years after herpes virus infections, including granulomatous dermatoses (most commonly granuloma annulare), leukemic and lymphomatous infiltrations, acneiform eruptions, and less commonly lichenoid reactions.3,7 abstract background: wolf’s isotopic response has been described in association with malignancy, infections, and inflammatory disorders. lichenoid tissue reactions are a rare but recognized example of this phenomenon; only 41 cases of zosteriform lichen planus exist in publication. this case adds to the minimal literature describing lichenoid inflammatory dermatosis compatible with wolf’s isotopic response. methods: a literature review was conducted along with a case description is presented. results: a man in his 30s with a history of herpes zoster presented with a pruritic rash on his left arm. clinical and histopathological evaluation were consistent with lichen planus in the distribution of a healed herpes zoster rash. the skin lesions improved after six weeks of treatment with clobetasol 0.05% ointment twice daily. conclusions: the presentation of lichen planus as wolf’s isotopic response is uncommon, but responsive to standard topical therapy. introduction skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 547 lichenoid tissue reactions are a rare but recognized example of wolf’s isotopic response. in a recent case series of 24 patients with clinical and historical findings compatible with wolf’s isotopic response, one patient was diagnosed with lichen planus (lp), one with lichen planopilaris, and three with lichen sclerosis et atrophicus.7 this case adds another example of a lichenoid inflammatory dermatosis compatible with wolf’s isotopic response to the literature. a man in his 30s presented with a twomonth history of a pruritic eruption on his left arm. he reported pain at the onset of the eruption, but otherwise denied fever, chills, diaphoresis, nausea, or weight loss. his medical history was significant for metastatic oropharyngeal squamous cell carcinoma previously treated with chemotherapy and radiation, currently undergoing pembrolizumab immunotherapy. he also reported a history of shingles and had been taking valacyclovir for two months prior to his current presentation. physical examination revealed erythematous and violaceous papules in a linear dermatomal distribution involving the left axilla, upper arm, and volar forearm (figure 1). the remainder of the physical exam was unremarkable. histopathology showed dermatitis with hyperkeratosis, acanthosis, prominent granular layer, and a lymphocytepredominant, band-like inflammatory infiltrate obscuring the dermal-epidermal junction (figure 2a, b). sawtoothing of the rete ridges and occasional dyskeratotic keratinocytes within the lower third of the epidermis were present. the papillary figure 1. violaceous papules in a dermatomal distribution dermis showed papillary dermal fibroplasia and scattered melanophages, and the dermis showed variable perivascular lymphocytic infiltrate. herpes viral immunostains and pcr for herpes simplex virus (hsv) and varicella zoster virus (vzv) dna were negative. presence of dermal melanophages in the biopsy indicated some chronicity to the lesion. the patient was treated with clobetasol 0.05% ointment twice daily to the affected areas. he required gabapentin to control his pruritus due to lack of response with oral antihistamines. he noted greater than ninety percent improvement in his eruption and pruritus after six weeks of therapy. lp classically presents as violaceous, intensely pruritic papules or plaques affecting the skin, mucous membranes, and nails. histopathology classically shows lichenoid inflammation, such as hyperkeratosis without parakeratosis, vacuolization of the basal layer, and bandlike lymphocytic infiltrate at the dermal case discussion skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 548 figure 2 a) biopsy specimen at original magnification x50 remarkable for hyperkeratosis, acanthosis, and sawtooth rete ridges b) biopsy specimen at original magnification x400 demonstrating dyskeratotic keratinocytes within the lower third of the epidermis and band-like lymphocytic infiltrate at dermal-epidermal junction epidermal junction. the clinical and histologic findings herein were compatible with lp in the distribution of a healed vzv infection, consistent with wolf’s isotopic response. literature review indicates at least 41 cases of zosteriform lp have been published.4,7,8 while poorly understood, the pathophysiology of this presentation is hypothesized to be caused by an immune reaction to antigenically altered keratinocytes after resolution of a vzv eruption, when vzv dna is no longer detectable via pcr.8 immune system dysregulation may also play a role in the latent expression of lp.9 other cases have suggested persistent vzv antigens, cutaneous nerve and microcirculation compromise, and neuropeptide secretion may precipitate zosteriform lp through interaction with the skin, and nervous and immune systems.1,8 the temporal delay between primary vzv eruption and the subsequent presentation of zosteriform lp can range from 15 days to five years. zosteriform lp only presenting after a recurrence of vzv has also been reported.8 the clinical and histologic findings in this case allowed us to conclude the patient’s eruption was not due to vzv itself. the clinical lack of vesicles or erosions and histological lack of chromatin margination, intranuclear inclusions, ballooning degeneration of keratinocytes, or intraepidermal vesiculation were inconsistent with a vzv eruption. although vzv resistance to acyclovir and its pro-drug valacyclovir has been reported in immunocompromised patients, pcr analysis further confirmed the absence of a resistant viral strain in this case.10 furthermore, although lp often resolves with significant post-inflammatory hyperpigmentation, the histologic evidence of lymphocytic infiltrate indicated the eruption was ongoing and not yet healed. skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 549 additional differential diagnoses for this case included linear lp, lichen striatus, and koebnerization of either. the koebner phenomenon is an isomorphic appearance of the same disease in previously unaffected areas of the skin secondary to trauma.11 similar to wolf’s isotopic response, the koebner phenomenon indicates the presence of lasting immune alterations and physiologic changes after extrinsic insult that may share similar underlying mechanisms. whereas linear lp is an isomorphic phenomenon clinically comparable to zosteriform lp12, lichen striatus presents as a largely asymptomatic, linear, unilateral, and hypopigmented eruption often involving extremities. all demonstrating lichenoid inflammation, these three presentations may be indistinguishable on histologic grounds alone; however, linear lp and lichen striatus follow the lines of blaschko rather than a dermatomal pattern. this patient’s eruption followed the c8 dermatome, which crosses several lines of blaschko. in this case, the histological absence of parakeratosis and significant spongiosis, and the presence of characteristic saw-tooth rete ridges favored lp, but this example nonetheless highlights the importance of using morphology in diagnostic dermatology. here, we report a rare case of active lp in the dermatomal distribution of resolved herpes zoster infection compatible with wolf’s isotopic response. although an uncommon presentation of lp, it was successfully treated with standard topical therapy once appropriately diagnosed. this case underscores the importance of incorporating historical, histologic, and morphological findings in clinical practice conflict of interest disclosures: none funding: none corresponding author: lucia seminario-vidal, md, phd 13330 usf laurel drive, 6th floor tampa, fl 33612 phone: 813-974-4744 fax: 813-332-0942 email: luciasem@usf.edu references: 1. wolf r, brenner s, ruocco v, filioli fg. isotopic response. int j dermatol. 1995;34(5):341-348. 2. wyburn-mason r. malignant change arising in tissues affected by herpes. br med j. 1955;2(4948):1106-1109. 3. ruocco v, brunetti g, puca rv, ruocco e. the immunocompromised district: a unifying concept for lymphoedematous, herpes-infected and otherwise damaged sites. j eur acad dermatol venereol. 2009;23(12):1364-1373. 4. wolf r, wolf d, ruocco v, ruocco e. wolf's isotopic response: the first attempt to introduce the concept of vulnerable areas in dermatology. clin dermatol. 2014;32(5):557-560. 5. liu ci, hsu ch. leukaemia cutis at the site of striae distensae: an isotopic response? acta derm venereol. 2010;90(4):422-423. 6. abraham z, feuerman ej, schafer i, feinmesser m. disseminated granuloma annulare following erythema multiforme minor. australas j dermatol. 2000;41(4):238-241. 7. wang t, zhang m, zhang y, et al. wolf's isotopic response after herpes zoster infection: a study of 24 new cases and literature review. acta derm venereol. 2019;99(11):953-959. 8. lora v, cota c, kanitakis j. zosteriform lichen planus after herpes zoster: report of a new case of wolf's isotopic phenomenon and literature review. dermatol online j. 2014;20(11). 9. requena l, kutzner h, escalonilla p, ortiz s, schaller j, rohwedder a. cutaneous reactions at sites of herpes conclusion skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 550 zoster scars: an expanded spectrum. br j dermatol. 1998;138(1):161-168. 10. sauerbrei a, taut j, zell r, wutzler p. resistance testing of clinical varicellazoster virus strains. antiviral res. 2011;90(3):242-247. 11. sagi l, trau h. the koebner phenomenon. clin dermatol. 2011;29(2):231-236. 12. happle r. 'zosteriform' lichen planus: is it zosteriform? dermatology. 1996;192(4):385-386. skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 503 2021 ucb® resident research competition – 2nd place original research parkinson’s disease as a risk factor for melanoma: a review lt zachary t. monahan, md1, lcdr aaron s. cantor, md1, cdr kent s. handfield, md, faad1 1walter reed national military medical center, bethesda, md characterizing the association between malignancy and parkinson’s disease (pd) has been an enormous challenge. while most malignancies are generally observed to be less common in patients with pd, melanoma appears to be a notable exception. many studies have evaluated the cellular and epidemiological connections, and most conclude that patients with pd are at a higher risk for developing melanoma.1– 14 genetic studies of melanoma and pd have complicated the picture, highlighting exceedingly complex pathogenic models for each disease. although the understanding of each particular disease has progressed, details of their relationship are elusive. the relationship between melanoma and pd seems natural, as both diseases involve the biological pigment melanin. in pd, neuromelanin depletion from the brain’s abstract objective: to review the literature and place into a quantified context the relationship of parkinson’s disease diagnosis to a subsequent diagnosis of malignant melanoma, and to briefly explore potential molecular associations between the two diseases. methods: the medline database was queried with terms related to parkinson’s disease (pd) and malignant melanoma, with use of boolean operator and to identify studies involving both diseases. studies were divided into primary and meta-analyses, with exclusive evaluation of those quantifying risk of malignant melanoma after an established diagnosis of parkinson’s disease. critical studies were identified using medline searches to identify established quantified risk metrics between classic melanoma risk factors and subsequent development of malignant melanoma. results: twelve primary studies and three meta-analyses were evaluated and their risk metrices tabulated. three studies offered estimated risk of development of malignant melanoma in patients with classic melanoma risk factors. these metrices were also tabulated and compared with the metrices established by the twelve primary studies. this demonstrated a similarity in overall risk of developing malignant melanoma in a patient with a diagnosis of parkinson’s disease as compared to a patient with classical melanoma risk factors. conclusion: it is wise to consider the presence of parkinson’s disease in a patient as one factor when clinicians decide on the appropriateness of regular full body screening examinations. introduction skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 504 substantia nigra (sn) is a disease hallmark.15–17 in melanoma, eumelaninproducing melanocytes are the malignant cells responsible for disease.18 these two pigment types share structural similarities, and there is evidence of shared synthetic pathways involving tyrosinase.19,20 while the association of both diseases with melanin is intriguing, it remains unclear whether this association is fundamentally related to their pathogenic relationship. though the precise molecular relationship continues to elude, further understanding the epidemiology of melanoma and pd may improve screening practices and prevent recent trends in melanoma overdiagnosis.21 the epidemiology of the two disorders considered together is critical for establishing accurate, evidence-based screening and diagnostic procedures. in this review, we first searched the medline database for studies evaluating the epidemiological link between pd and any form of melanoma, regardless of the time of publication or the particular demographic studied. results were divided into primary studies and meta-analyses and reviewed separately. only those primary studies that specifically addressed the increased risk of melanoma after an established pd diagnosis were evaluated further. these primary studies were analyzed for the components of their analyses that addressed this specific association. corresponding risk metrics were tabulated for each of these studies. we also searched the medline database for recent primary studies and metaanalyses evaluating the strength of individual clinical risk factors for developing melanoma. the approximate degree of risk increase for each risk factor was tabulated based on recent meta-analyses to compare the degree of the increased risk of melanoma reported in patients with diagnosed pd. the epidemiology of pd and melanoma is directly relevant to the daily practice of a clinical dermatologist. a quantitative appreciation for melanoma incidence helps answer the following questions: 1. how much elevated risk are patients with pd at for developing melanoma? 2. how does this elevated risk compare to traditional melanoma risk factors? 3. do skin screening practices need to change based on a pd diagnosis? 4. do patients with melanoma deserve closer monitoring for early symptoms of pd? the quantitative epidemiologic association must be considered with regard to the natural history of both diseases. for early detection and screening for melanoma, we focused on the risk of any melanoma after an established pd diagnosis. several primary epidemiologic studies and meta-analyses have attempted to quantify the relationship between pd and a subsequent diagnosis of melanoma (table 1), with the association measures referencing the risk of melanoma diagnosis in a patient with a pre-established pd diagnosis.1,3–10,12,14,22 methods results skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 505 systematic meta-analyses have supported the conclusions of primary studies, strengthening the epidemiologic association by ensuring adequate controls across studied populations for potential confounders, such as age and gender. huang et al. 2015 showed a pooled odds ratio of developing melanoma of 2.43 (95% ci: 1.77-3.32) for pd patients compared to those without, as determined across multiple studies.13 similarly, liu et al. 2011 found a pooled odds ratio of 3.61 (95% ci: 1.49– 8.77).11 an extensive metanalysis by bajaj et al. in 2010 suggested a pooled relative risk of 1.41 (95% ci: 0.90-2.19).2 understanding the above data in the context of other, more classic melanoma risk factors becomes critical to making evidence-based decisions. despite the disagreement among specialties, task forces, and societies in the u.s. and abroad regarding the frequency and timing of full body skin exams, many dermatologists recommend full-body skin exams for patients who are at notably increased risk for melanoma.23,24 some of the widely accepted melanoma risk factors include light skin and eye color, patients with multiple atypical nevi, a history of severe sunburns, and a history of prior treated melanomas.25–27 the most recent prospective cohort study in australia found the highest hazard ratios of invasive melanoma to be 2.34 for age >65, 2.13 for the male gender, 4.79 for inability to tan, 4.42 for many moles at age 21, and 2.51 for >21 moles removed in the past. this study stratified risk for both invasive melanomas and any melanoma.28 similar findings are reflected in a recent analysis of the american academy of dermatology’s (aad) skin cancer screening program. this analysis found the odds ratios for the development of melanoma to be 1.2 for those over age 50, 1.4 for males, 1.4 for the presence of changing moles, 2.0 for the absence of regular visits to a dermatologist, and 3.5 for a history of melanoma. when combined, exposures to several of these risk factors resulted in an odds ratio of 1.0, 1.7, 2.5, and 4.4 for zero to one, two, three, and four to five risk factors, respectively. the “age over 50 years” risk factor may seem to capture the older population associated with a higher risk for pd diagnosis. however, compared to risk metrics for developing melanoma after pd diagnosis, this criterion appears to carry at least half the risk and, by itself, is unlikely to prompt a primary care referral to dermatology for a full-body skin exam.29 the most recent and most extensive analysis of the aad spotme skin cancer screening program found the adjusted odds ratio for cutaneous melanoma to be 1.54 for males, 1.38 for patient’s with an uninsured status, 1.28 for patients with no regular access to a dermatologist, 2.54 for personal history of melanoma, 1.65 for a recent change in moles, 1.68 for >26 moles, 1.44 for >30 hours per week in the sun, and 1.39 for 4-6 years of indoor tanning. beaulieu et al. concluded that targeting these groups will lead to more effective screening campaigns.30 table 2 summarizes the above risk metrics and their ranges to compare the metrics reported in table 1. the magnitude of increased for melanoma risk in patients with a pd diagnosis over multiple studies approximates the increased risk for melanoma in patients with multiple classic risk factors, including such critical elements of a patient’s history as a previous melanoma diagnosis. these standard risk factors would typically prompt more thorough and regular skin exams by a dermatologist. citing this evidence, we advocate for periodic skin exams for people skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 506 with pd, even in the absence of the above more classically appreciated risk factors, patients who would otherwise go unchecked. the requisite shared decision table 1. the relationship between pd and a subsequent diagnosis of melanoma. authors publication date study design risk metric (95% ci) moller et al. march 1995 retrospective cohort rr: 1.96 (1.1-3.2) olsen et al. december 2004 retrospective cohort sir: 1.95 (1.4-2.6) constantinescu et al. april 2007 retrospective cohort ser: 3.3 (1.1-7.8) driver et al. june 2007 prospective cohort rr: 6.15 (1.77-21.37) bertoni et al. march 2010 prospective cohort rr: 2.24 (1.21-4.17) becker et al. march 2010 case-control or: 2.72 (0.66-11.12) lo et al. september 2010 retrospective cohort rr: 1.6 (0.71-3.6) schwid et al. september 2010 prospective cohort sir: 20.9 (9.6-39.7) sun et al. october 2011 prospective cohort hr: 2.11 (0.21-21.3) rugbjerg et al. october 2013 prospective cohort sir: 1.41 (1.09-1.34) constantinescu et al. december 2013 prospective cohort ser: 3.6 (2.2-5.6) ryu et al. april 2020 retrospective cohort hr: 2.83 (1.39-5.72) odds ratio (or), standardized event ratio (ser), relative risk (rr), standardized incidence ratio (sir), hazard ratio (hr). table 2. summary of risk metric ranges for commonly considered risk factors for the development of melanoma reported by several recent studies. study risk metric range for all risk factors evaluated olsen et al. 2018 hr: 2.13-4.79 goldberg et al. 2007 or: 1.2-3.5 beaulieu et al. 2018 or: 1.28-2.54 odds ratio (or), relative risk (rr), hazard ratio (hr). must recognize that the risks of full body skin exams and unnecessary procedures include anxiety from overly frequent monitoring and possible increased costs to personal and public insurance systems. these risks are especially important to consider since not all melanomas follow a predictable path, and early detection may not always improve outcomes. the epidemiologic association between pd and melanoma belies a molecular relationship that has so far remained incompletely characterized. a short list of the commonly associated genes with both melanoma and pd is offered in table 3.31,32 the absence of common entries is telling; suggested molecular connections between pd and melanoma are numerous but convincing evidence remains scarce. table 4 outlines some of the prominent suggested molecular connections.34-50 recent literature is accelerating our understanding of this molecular relationship, and multiple potential connections between the two diseases exist. several of the molecular candidates outlined in table 4 are critical players in various protein quality control (pqc) pathways, suggesting that a more developed understanding of this process has the potential to improve understanding of both diseases. the molecular links between the two diseases, however, remains mostly academic. it remains to be seen if understanding the pathways will lead to the identification of new therapies, or otherwise meaningfully improve our ability to combat the human costs of either disease. while studies continue, there are essential things discussion skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 507 that we can do in the clinic now, armed with our knowledge of the association of pd and melanoma. table 3. proteins and their respective genes are linked to increased susceptibility to melanoma and parkinson’s disease proteins (genes) linked to melanoma adrenocortical dysplasia homologue (acd) brca-associated protein 1 (bap1) cyclin-dependent kinase inhibitor 2a (cdkn2a) cyclin-dependent kinase 4 (cdk4) micropthalmia-associated transcription factor (mitf) melanocortin 1 receptor (mc1r) protection of telomeres 1 (pot1) telomerase reverse transcriptase (tert) terf2-interacting protein (terf2ip) proteins (genes) linked to pd alpha-synuclein (snca) dardarin (lrrk2) f-box only protein 7 (fbxo7) microtubule-associated protein tau (mapt) paired immunoglobulin type 2 receptor beta (pilrb) parkin (park2) protein deglycase dj-1 (park7) pten-induced kinase 1 (pink1) siglec 3 (cd33) based on our review, a diagnosis of pd is a significant risk factor for melanoma. we suggest that the timing and frequency of fullbody skin exams are thoughtfully considered for patients diagnosed with pd. while the clinical utility of full-body skin exams in the general population with few to no risk factors for melanoma remains ambiguous, consistent epidemiologic evidence included herein suggests a likely benefit in patients with pd. the diagnosis of pd increases the subsequent risk of developing melanoma at rates similar to established melanoma risk factors, and it should be added to the list of risk factors considered during screening. given the relative ease, speed, and low risks of a full-body skin exam, dermatologists can directly benefit patients with a diagnosis of pd, lead the specialty in improving our understanding of melanoma, and challenge the field to consider novel factors in melanoma pathogenesis. other authors have made similar recommendations.33 with such targeting toward higher-risk patients, melanoma screenings will be optimized, increasing detection in higher-risk populations and decreasing overdiagnosis. a more accurate set of risk factors can also help establish a consensus risk threshold to guide screening practices, which has been done in australia.28 finally, our review highlights the need for future studies to characterize the molecular link between melanoma and pd and the outcomes of melanoma diagnosed in patients with pd, such as the stage of melanoma at diagnosis and the relative survival of these patients. these future studies will help us better understand both conclusion skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 508 table 4. proteins and their respective genes are proposed as potential links between pd and melanoma in the literature gene protein proposed link snca alpha-synuclein mutations in snca are rare.34,35 alpha-synuclein’s association with pd is primarily histopathological; abnormal inclusions of alpha-synuclein into so-called lewy bodies are a disease hallmark. while mutations can be associated with increased risk, the alphasynuclein in lewy bodies is often genetically wildtype.36 increased levels of alpha-synuclein have also recently been found in melanoma cells.34,37 park2 parkin an e3 ligase, parkin has been linked to pd in, with sequence mutations being important to the association.38,39 in fact, mutations in park2 are the most frequent cause of autosomal recessive juvenileonset pd.34,40 the studies of parkin in the context of melanoma have been mixed; some results suggest that it may function as a tumor suppressor in melanoma cell lines,41 while others have suggested that parkin may promote melanoma proliferation.42 lrrk2 dardarin architectural similarities exist between the kinase domain of dardarin and the protein braf.43 braf is encoded by braf, which is the most common site of somatic mutations in melanoma.44 the kinase domain of dardarin has been implicated in pd pathogenesis,45 with sequence mutations in this gene being the most common cause of autosomal dominant pd.34,46 park7 dj-1 the protein deglycase dj-1 has been associated with pd, with data suggesting that it interacts with alpha-synuclein to prevent its adoption into pathologic conformations.47 results from dj-1 knockout mice suggest that loss of dj-1 function enhances melanoma metastasis.48 pink1 pink1 implicated in the degradation of abnormal mitochondria, mutations in pink1 have an association with pd.49 it is also associated with malignancy development in general, with evidence that mutations in pink1 promote tumorigenesis and metastasis.50 diseases' underlying pathology and promote more accurate prognostic models. abbreviations: pd: parkinson’s disease pqc: protein quality control sn: substantia nigra conflict of interest disclosures: the authors have no conflict of interest to declare. no prior presentation of data to report. drs. monahan, cantor, and handfield are military service members of the u.s. government. this work was prepared as part of their official duties. title 17, usc, § 105 provides that copyright protection under this title is not available for any work of the u.s. government. title 17, usc § 101 defines a u.s. government work as a work prepared by a military service member or employee of the u.s. government as part of that person’s official duties. the views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the department of the navy, department of defense, or the united states government. funding: none skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 509 corresponding author: aaron s. cantor, md lcdr, mc (fmf), usn pgy-3, national capital consortium dermatology residency program walter reed national military medical center 4494 north palmer road, bethesda, md 20889 phone: (301) 400-0466 email: aaron.s.cantor.mil@mail.mil references: 1. driver ja, logroscino g, buring je, gaziano jm, kurth t. a prospective cohort study of cancer incidence following the diagnosis of parkinson’s disease. cancer epidemiol biomarkers prev. 2007;16(6):1260-1265. doi:10.1158/1055-9965.epi-07-0038 2. bajaj a, driver ja, schernhammer es. parkinson’s disease and cancer risk: a systematic review and meta-analysis. cancer causes control. 2010;21(5):697-707. doi:10.1007/s10552-009-9497-6 3. sun l-m, liang j-a, chang s-n, sung f-c, muo c-h, kao c-h. analysis of parkinson’s disease and subsequent cancer risk in taiwan: a nationwide population-based cohort study. neuroepidemiology. 2011;37(2):114-119. doi:10.1159/000331489 4. schwid sr, bausch j, oakes d, et al. cancer incidence in a trial of an antiapoptotic agent for parkinson’s disease. mov disord. 2010;25(12):1801-1808. doi:10.1002/mds.23006 5. becker c, brobert gp, johansson s, jick ss, meier cr. cancer risk in association with parkinson disease: a population-based study. parkinsonism relat disord. 2010;16(3):186190. doi:10.1016/j.parkreldis.2009.11.005 6. lo ry, tanner cm, van den eeden sk, albers kb, leimpeter ad, nelson lm. comorbid cancer in parkinson’s disease. mov disord. 2010;25(12):1809-1817. doi:10.1002/mds.23246 7. bertoni jm, arlette jp, fernandez hh, et al. increased melanoma risk in parkinson disease: a prospective clinicopathological study. arch neurol. 2010;67(3):347-352. doi:10.1001/archneurol.2010.1 8. constantinescu r, romer m, kieburtz k, datatop investigators of the parkinson study group. malignant melanoma in early parkinson’s disease: the datatop trial. mov disord. 2007;22(5):720-722. doi:10.1002/mds.21273 9. constantinescu r, elm j, auinger p, et al. malignant melanoma in early-treated parkinson’s disease: the net-pd trial. mov disord. 2014;29(2):263-265. doi:10.1002/mds.25734 10. rugbjerg k, friis s, lassen cf, ritz b, olsen jh. malignant melanoma, breast cancer and other cancers in patients with parkinson’s disease. int j cancer. 2012;131(8):1904-1911. doi:10.1002/ijc.27443 11. liu r, gao x, lu y, chen h. meta-analysis of the relationship between parkinson disease and melanoma. neurology. 2011;76(23):20022009. 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nat genet. 2000;25(3):302-305. doi:10.1038/77060 39. li n, wang l, zhang j, et al. whole-exome sequencing in early-onset parkinson’s disease among ethnic chinese. neurobiol aging. skin september 2021 volume 5 issue 5 copyright 2021 the national society for cutaneous medicine 511 2020;90:150.e5-150.e11. doi:10.1016/j.neurobiolaging.2019.12.023 40. kitada t, asakawa s, hattori n, et al. mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. nature. 1998;392(6676):605-608. doi:10.1038/33416 41. hu h-h, kannengiesser c, lesage s, et al. parkin inactivation links parkinson’s disease to melanoma. j natl cancer inst. 2016;108(3). doi:10.1093/jnci/djv340 42. lee ys, jung yy, park mh, et al. deficiency of parkin suppresses melanoma tumor development and metastasis through inhibition of mfn2 ubiquitination. cancer lett. 2018;433:156-164. doi:10.1016/j.canlet.2018.07.007 43. pan t, li x, jankovic j. the association between parkinson’s disease and melanoma: association between pd and melanoma. int j cancer. 2011;128(10):2251-2260. doi:10.1002/ijc.25912 44. davies h, bignell gr, cox c, et al. mutations of the braf gene in human cancer. nature. 2002;417(6892):949-954. doi:10.1038/nature00766 45. smith ww, pei z, jiang h, dawson vl, dawson tm, ross ca. kinase activity of mutant lrrk2 mediates neuronal toxicity. nat neurosci. 2006;9(10):1231-1233. doi:10.1038/nn1776 46. di fonzo a, rohé cf, ferreira j, et al. a frequent lrrk2 gene mutation associated with autosomal dominant parkinson’s disease. lancet. 2005;365(9457):412-415. doi:10.1016/s0140-6736(05)17829-5 47. zondler l, miller-fleming l, repici m, et al. dj-1 interactions with α-synuclein attenuate aggregation and cellular toxicity in models of parkinson’s disease. cell death dis. 2014;5:e1350. doi:10.1038/cddis.2014.307 48. chien c-h, lee m-j, liou h-c, liou h-h, fu w-m. local immunosuppressive microenvironment enhances migration of melanoma cells to lungs in dj-1 knockout mice. plos one. 2015;10(2):e0115827. doi:10.1371/journal.pone.0115827 49. narendra dp, jin sm, tanaka a, et al. pink1 is selectively stabilized on impaired mitochondria to activate parkin. green dr, ed. plos biol. 2010;8(1):e1000298. doi:10.1371/journal.pbio.1000298 50. o’flanagan ch, morais va, wurst w, de strooper b, o’neill c. the parkinson’s gene pink1 regulates cell cycle progression and promotes cancer-associated phenotypes. oncogene. 2015;34(11):1363-1374. doi:10.1038/onc.2014.81 acknowledgements study funded by galderma r&d; poster/editorial support provided by galderma laboratories, l.p. introduction facial skin of those with rosacea is characterized by chronic barrier disruption that results in increased sensitivity, especially to many skincare products. regular use of a moisturizer by patients with rosacea can help alleviate skin dryness and restore skin barrier function. however, care must be taken by this population to ensure selected products do not cause further irritation and potentially induce rosacea flares. a facial moisturizer designed for night time use has been specifically developed for patients with redness-prone skin (cetaphil night moisturizer [cnm]). this formula is fragrance free and contains ingredients to help moisturizer and restore barrier function such as ceramide np, vitamin e, allantoin, and licorice root extract among others. the results of 2 clinical studies that assessed the efficacy and tolerability of cnm are presented here. subjects and methods study 1: hydration and skin barrier function • men and women with dry volar forearms • inner forearms randomized to treated and control • 40 mg of product applied to 20 cm2 corneometer and transepidermal water loss (tewl) assessed at baseline and 2, 4, 8, and 24 hours study 2: in use efficacy and tolerability • men or women with rosacea and mild to moderate non-transient erythema • product applied qd in the evening for 3 weeks • assessments made on day 1 before application, day 1 30 minutes after first use and days 8, and 22 before product application objective (chromameter) and subjective (investigator and subject) assessment of redness investigator and subject tolerability assessments · redness and tolerability assessments made on a 5 point scale of 0 (none), 0.5 (very slight), 1 (slight), 2 (moderate) and 3 (strong) subject satisfaction performance of a facial night moisturizer designed for redness-prone skin matthew h meckfessel, phd1; sandrine teissedre, msc2; nadege lachmann3; francine santoro, md3 1galderma laboratories, l.p., fort worth, texas; 2galderma r&d, sophia antipolis, france; 3galderma r&d, egerkingen, switzerland cet.p-rd105328-01 summary cnm significantly improves skin hydration and skin barrier function and is an ideal nightly facial moisturizer for patients with rosacea results skin hydration and skin barrier function significantly improved for 24 and 8 hours, respectively, compared to untreated and baseline (figures 1 and 2). for the in use study, 33 women enrolled and completed the study with a mean age of 54.4 years. there was a significant improvement of erythema during the study as assessed by investigators and subjects (figure 3). however, this change was not confirmed by instrumental measurement with the chromameter and is not clinically relevant (data not shown). the product was well tolerated with mean scores for all parameters less than mild (data not shown). subjects demonstrated high satisfaction with the product (figure 4). one mild adverse event of diarrhea was reported and was considered unrelated by the investigator. m ea n co rn eo m et er (a .u .) cnm control area hour 0 20 25 30 35 40 45 50 55 60 4 8 12 16 20 24 * * * *p < .05 vs baseline * m ea n sc or e investigator subject baseline baseline, 30 minutes day 8 day 22 0 1 2 3 *p < .05 vs baseline * * * * disagree neutral agree percent of subjects overall, i like the product very much feel my skin is nourished suitable for sensitive skin leaves skin soft and smooth 0 50 6010 20 30 40 70 80 90 21.2 66.7 12.1 9.1 78.8 12.7 9.1 84.8 6.1 9.1 75.8 12.1 p < .05 for agree vs disagree for all * * * m ea n te w l (g /m 2h ) hour 0 0 2 4 6 8 10 4 8 12 16 20 24 cnm control area *p < .05 vs baseline figure 4. subject satisfaction with cnm (n=33) figure 1. corneometry assessments figure 2. tewl assessments figure 3. investigator and subject assessed skin redness (n=33) fc17postergaldermameckfesselfacialnightmoisturizer.pdf powerpoint presentation presented at fall clinical dermatology conference 2022 meeting, october 20–23, 2022, las vegas, nv, usa acknowledgements • this study was supported by arcutis biotherapeutics, inc. • thank you to the investigators and their staff for their participation in the trial • we are grateful to the study participants and their families for their time and commitment • writing support was provided by christina mcmanus, phd, and lauren ramsey, pharmd, alligent biopharm consulting llc, and funded by arcutis biotherapeutics, inc. disclosures lkf, aa, jd, zdd, mg, ml, kap, js, and lsg are investigators and/or consultants for arcutis biotherapeutics, inc. and received grants/research funding and/or honoraria; dk, rch, pb, and drb are employees of arcutis biotherapeutics, inc. additional disclosures provided on request. introduction • patients with psoriasis involving special areas, such as the face, intertriginous, and genital areas, may have a disproportionately greater negative impact on their quality of life than patients without psoriasis involvement in those areas1 • chronic use of current topical treatment options in these areas is limited due to risk of local skin side effects or limitations on duration of use2 • roflumilast is a selective and highly potent phosphodiesterase 4 (pde4) inhibitor with greater affinity for pde4 than apremilast or crisaborole and approximately 25to >300-fold more potent based on in vitro assays3 – topical roflumilast is being investigated as a once-daily, nonsteroidal treatment for long-term management of various dermatologic conditions, including atopic dermatitis, seborrheic dermatitis, and chronic plaque psoriasis (approved by the us food and drug administration july 29, 2022) • efficacy, safety, and tolerability of roflumilast cream 0.3% in psoriasis have been demonstrated in a phase 2b study in patients with psoriasis; the individual phase 3 dermis-1 and dermis-2 results were previously reported4,5 • here, we report the pooled results from 2 phase 3, randomized, doubleblind, vehicle-controlled, multicenter trials of once-daily roflumilast cream 0.3% in patients with psoriasis (dermis-1 and dermis-2), presenting subgroup analyses of patients with involvement of special areas (sas: defined as the face, and/or intertriginous, and/or genital areas) methods • dermis-1 and dermis-2 were 2 identical, phase 3, randomized, doubleblind, vehicle-controlled, 8-week studies of once-daily roflumilast cream 0.3% in patients (≥2 years of age) with psoriasis (body surface area [bsa] affected: 2%–20%; figure 1) • the primary efficacy endpoint was investigator global assessment (iga) success at week 8, which was defined as achievement of clear or almost clear iga status plus ≥2-grade improvement from baseline conclusions • roflumilast cream 0.3% provided improvement across multiple efficacy endpoints versus vehicle cream while demonstrating favorable safety and tolerability in patients with chronic plaque psoriasis involving intertriginous, and/or face, and/or genital areas in 2 phase 3 trials • the local tolerability profile as assessed by both patients and investigators was favorable • the subgroup analysis of the pooled results of the phase 3 dermis-1 and dermis-2 trials showed that once-daily roflumilast cream 0.3% demonstrated efficacy and tolerability in patients with psoriasis involvement in difficult-to-treat areas results • baseline disease characteristics and demographics were similar across treatment groups (table 1) • significantly more roflumilast-treated patients achieved the primary endpoint, iga success at week 8 (figure 2) – across the subgroups at week 8, a greater percentage of patients in the roflumilast group achieved iga success compared with that of the vehicle group – more patients in the roflumilast group also had an iga status of clear or almost clear across subgroups at week 8 (figure 3) • more roflumilast-treated patients who had a baseline score ≥4 on the worst itch numeric rating scale (wi-nrs) had a 4-point improvement at week 8 across subgroups (figure 4) • the least square mean percent change from baseline in psoriasis symptoms diary (psd) scores was greater after roflumilast treatment than with vehicle treatment at week 8 across subgroups (figure 5) safety • in patients with involvement in sa, local tolerability was highly favorable as reported by patient and investigator assessment of irritation, burning, and stinging (figure 6) – ≥97.6% of patients had no evidence of irritation at week 8 on investigator-rated assessments – ≥97.2% reported no warmth/tingling sensation or mild sensation at week 8 on patient-rated assessments • overall incidence of treatment-emergent adverse events (teaes), serious aes, and teaes leading to discontinuation was low with similar rates between roflumilast and vehicle across both studies • no skin atrophy was seen in the sas treated with topical roflumilast or vehicle (table 2) laura k. ferris,1 april armstrong,2 james del rosso,3 zoe d. draelos,4 melinda gooderham,5 mark lebwohl,6 kim a. papp,7 jennifer soung,8 linda stein gold,9 david krupa,10 robert c. higham,10 patrick burnett,10 david r. berk10 1university of pittsburgh, department of dermatology, pittsburgh, pa, usa; 2keck school of medicine, department of dermatology, university of southern california los angeles, ca, usa; 3jdr dermatology research center, llc, las vegas, nv, usa; 4dermatology consulting services, high point, nc, usa; 5skin centre for dermatology, probity medical research and queen’s university, peterborough, on, canada; 6icahn school of medicine at mount sinai, new york, ny, usa; 7probity medical research and k papp clinical research, waterloo, on, canada; 8southern california dermatology, santa ana, ca, usa; 9henry ford medical center, detroit, mi, usa; 10arcutis biotherapeutics, inc., westlake village, ca, usa efficacy and tolerability of roflumilast cream 0.3% in patients with chronic plaque psoriasis involvement on the face, intertriginous, or genital areas: pooled results from phase 3 trials (dermis-1 and dermis-2) figure 1. study design iga success = clear or almost clear iga status plus ≥2-grade improvement from baseline. bsa: body surface area; iga: investigator global assessment; i-iga: intertriginous iga; psd: psoriasis symptoms diary; qd: once daily; sa: special areas (sa: defined as the face, and/or intertriginous, and/or genital areas); wi-nrs: worst itch numeric rating scale. endpoints primary • iga success at week 8 secondary • i-iga success • wi-nrs • psd safety and tolerability eligibility • at least mild plaque psoriasis • age 2+ years • 2%–20% bsa roflumilast cream 0.3% qd n=576 vehicle cream qd n=305 8 weeks dosing visits: weeks 2, 4, 8 2:1 ra nd om iz e po st -h oc a na ly si s sa in vo lv em en t roflumilast cream 0.3% qd n=218 vehicle cream qd n=111 dermis-1 n=439 nct04211363 dermis-2 n=442 nct04211389 two identical, parallel, phase 3 multicenter trials table 1. baseline demographics and disease characteristics n (%) roflumilast cream 0.3% (n=576) vehicle (n=305) age in years, mean (sd) 47.2 (14.6) 47.9 (15.0) sex, n (%) male 365 (63.4) 196 (64.3) female 211 (36.6) 109 (35.7) race, n (%) american indian or alaska native 4 (0.7) 2 (0.7) asian 41 (7.1) 20 (6.6) black or african american 21 (3.6) 17 (5.6) native hawaiian or other pacific islander 5 (0.9) 1 (0.3) white 474 (82.3) 250 (82.0) not reported 9 (1.6) 5 (1.6) other 19 (3.3) 9 (3.0) more than 1 race 3 (0.5) 1 (0.3) iga score, n (%) 2 (mild) 101 (17.5) 44 (14.4) 3 (moderate) 426 (74.0) 240 (78.7) 4 (severe) 49 (8.5) 21 (6.9) psoriasis-affected bsa, mean % (sd) 6.7 (4.6) 7.6 (4.9) i-iga score, n (%) 1 (almost clear) 7 (1.2) 2 (0.7) 2 (mild) 58 (10.1) 29 (9.5) 3 (moderate) 54 (9.4) 33 (10.8) 4 (severe) 4 (0.7) 1 (0.3) pasi, mean score (sd) 6.4 (3.2) 6.9 (3.6) wi-nrs, mean score (sd) 5.7 (2.7) 5.9 (2.8) wi-nrs score ≥4, n (%) 447 (77.6) 231 (75.7) bsa: body surface area; iga: investigator global assessment; i-iga: intertriginous iga; pasi: psoriasis area severity index; wi-nrs: worst itch numeric rating scale; sd: standard deviation. table 2. overall aes6 n (%) roflumilast cream 0.3% (n=576) vehicle (n=305) patients with any teae 147 (25.5) 64 (21.0) patients with any treatment-related teae 23 (4.0) 11 (3.6) patients with any sae 2 (0.3) 2 (0.7) patients who discontinued study due to ae 6 (1.0) 4 (1.3) most common teae (≥1% in the roflumilast group), preferred term diarrhea 18 (3.1) 0 headache 14 (2.4) 3 (1.0) insomnia 8 (1.4) 2 (0.7) nausea 7 (1.2) 1 (0.3) nasopharyngitis 6 (1.0) 4 (1.3) urinary tract infection 6 (1.0) 2 (0.7) application-site pain 6 (1.0) 1 (0.3) upper respiratory tract infection 6 (1.0) 1 (0.3) ae: adverse event; sae: serious adverse event; teae: treatment-emergent adverse event. figure 6. investigatorand patient-rated local tolerability at week 8 patient-rated tolerability: 0 = none (no sensation), 1 = mild (slight warm, tingling sensation), 2 = moderate (definite warm, tingling sensation), 3 = severe (hot, tingling/stinging sensation). 98.6 97.6 98.4 95.0 100.098.4 99.1 100.0 96.9 98.1 0 10 20 30 40 50 60 70 80 90 100 overall pooled dermis intertriginous, facial, genital involvement facial involvement genital involvement intertriginous involvement roflumilast cream 0.3% vehicle cream 99.5 98.9 98.3 97.3 98.998.8 98.2 98.6 97.2 98.2 0 10 20 30 40 50 60 70 80 90 100 overall pooled dermis intertriginous, facial, genital involvement facial involvement genital involvement intertriginous involvement roflumilast cream 0.3% vehicle cream investigator-rated local tolerability % patients with no evidence of irritation patient-rated local tolerability % patients with no or mild sensation pa ti en ts , % pa ti en ts , % references 1. merola jf, et al. dermatol ther 2018;31:e12589. 2. elmets ca, et al. j am acad dermatol 2021;84:432–470. 3. dong c, et al. j pharmacol exp ther 2016;358:413–422. 4. lebwohl mg, et al. n engl j med 2020;383:229–239. 5. lebwohl mg, et al. 30th congress of the european academy of dermatology and venereology (eadv) virtual, september 29–october 2, 2021. 6. lebwohl mg, et al. american academy of dermatology (aad), boston, ma, march 25–29, 2022. figure 4. percentage of patients achieving wi-nrs success at week 8 *p<0.05; **p<0.01; ***p<0.001; ****p<0.0001. wi-nrs success = ≥4-point improvement in patients with baseline wi-nrs score ≥4. ci: confidence interval; wi-nrs: worst itch numeric rating scale. figure 5. ls mean percent change in psd at week 8 *p<0.05; **p<0.01; ***p<0.001; ****p<0.0001. ci: confidence interval; ls: least square; psd: psoriasis symptoms diary. overall any sa facial genital intertriginous 0 10 20 30 40 50 60 70 80 90 100 % p at ie nt s (9 5% c i) **** * ***** **** roflumilast cream 0.3% vehicle n= 397 198 174 488085 106 55 69 30 patients with psoriasis involving overall any sa facial genital intertriginous –100 –90 –80 –70 –60 –50 –40 –30 –20 –10 0 ls m ea n pe rc en t ch an ge (9 5% c i) **** **** **** ****** roflumilast cream 0.3% vehicle n= 506 253 211 5597108 127 75 82 35 patients with psoriasis involving figure 3. percent of patients with involvement in sas achieving iga status of clear or almost clear (a) and i-iga clear or almost clear (b) at week 8 *p<0.05; **p<0.01; ***p<0.001; ****p<0.0001. i-iga clear or almost clear iga status evaluated in intertriginous areas only. ci: confidence interval; iga: investigator global assessment; i-iga: intertriginous iga; sa: special area. figure 2. percent of patients with involvement in sas achieving iga success (a) and i-iga success (b) at week 8 *p<0.05; **p<0.01; ***p<0.001; ****p<0.0001. iga success = clear or almost clear iga status plus ≥2-grade improvement from baseline; i-iga success = clear or almost clear iga status plus ≥2-grade improvement from baseline evaluated in intertriginous areas only. ci: confidence interval; iga: investigator global assessment; i-iga: intertriginous-iga; sa: special areas. overall any sa facial genital intertriginous 0 10 20 30 40 50 60 70 80 90 100 pa ti en ts , % (9 5% c i) **** **** ********** roflumilast cream 0.3% vehicle n= 519 263 218 5699111 133 76 84 37 patients with psoriasis involving a iga clear or almost clear b i-iga clear or almost clear intertriginous area only 0 10 20 30 40 50 60 70 80 90 100 pa ti en ts , % (9 5% c i) roflumilast cream 0.3% vehicle 99 56n= overall any sa facial genital intertriginous 0 10 20 30 40 50 60 70 80 90 100 % p at ie nt s (9 5% c i) **** **** ****** **** n= 519 263 218 5699111 133 76 84 37 roflumilast cream 0.3% vehicle patients with psoriasis involving intertriginous area only 0 10 20 30 40 50 60 70 80 90 100 pa ti en ts , % (9 5% c i) ** 99 56n= roflumilast cream 0.3% vehicle a. iga success b. i-iga success efficacy and tolerability of roflumilast cream 0.3% in patients with chronic plaque psoriasis involvement on the face, intertriginous, or genital areas: pooled results from phase 3 trials (dermis-1 and dermis-2) << /ascii85encodepages false /allowtransparency false /autopositionepsfiles true /autorotatepages /none /binding /left /calgrayprofile (dot gain 20%) /calrgbprofile (srgb iec61966-2.1) /calcmykprofile (u.s. web coated \050swop\051 v2) /srgbprofile (srgb iec61966-2.1) /cannotembedfontpolicy /warning /compatibilitylevel 1.3 /compressobjects /off /compresspages false /convertimagestoindexed true /passthroughjpegimages true /createjobticket false /defaultrenderingintent /default /detectblends true /detectcurves 0.0000 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on 'epg upload'] [based on 'epg upload'] [based on 'highresolution_nocrops'] [based on 'highresolution_nocrops'] [based on 'highresolution_nocrops\\0501\\051'] [based on 'highresolution_withcrops'] [based on '[pdf/x-1a:2001]'] use these settings to create adobe pdf documents that are to be checked or must conform to pdf/x-1a:2001, an iso standard for graphic content exchange. for more information on creating pdf/x-1a compliant pdf documents, please refer to the acrobat user guide. created pdf documents can be opened with acrobat and adobe reader 4.0 and later.) >> /namespace [ (adobe) (common) (1.0) ] /othernamespaces [ << /asreaderspreads false /cropimagestoframes true /errorcontrol /warnandcontinue /flattenerignorespreadoverrides false /includeguidesgrids false /includenonprinting false /includeslug false /namespace [ (adobe) (indesign) (4.0) ] /omitplacedbitmaps false /omitplacedeps false /omitplacedpdf false /simulateoverprint /legacy >> << /addbleedmarks false /addcolorbars false /addcropmarks false /addpageinfo false /addregmarks false /bleedoffset [ 0 0 0 0 ] /convertcolors /converttorgb /destinationprofilename (srgb iec61966-2.1) /destinationprofileselector /usename /downsample16bitimages true /flattenerpreset << /presetselector /highresolution >> /formelements false /generatestructure true /includebookmarks false /includehyperlinks false /includeinteractive false /includelayers false /includeprofiles false /marksoffset 0 /marksweight 0.250000 /multimediahandling /useobjectsettings /namespace [ (adobe) (creativesuite) (2.0) ] /pdfxoutputintentprofileselector /documentcmyk /pagemarksfile /romandefault /preserveediting true /untaggedcmykhandling /usedocumentprofile /untaggedrgbhandling /leaveuntagged /usedocumentbleed false >> << /allowimagebreaks true /allowtablebreaks true /expandpage false /honorbaseurl true /honorrollovereffect false /ignorehtmlpagebreaks false /includeheaderfooter false /marginoffset [ 0 0 0 0 ] /metadataauthor () /metadatakeywords () /metadatasubject () /metadatatitle () /metricpagesize [ 0 0 ] /metricunit /inch /mobilecompatible 0 /namespace [ (adobe) (golive) (8.0) ] /openzoomtohtmlfontsize false /pageorientation /portrait /removebackground false /shrinkcontent true /treatcolorsas /mainmonitorcolors /useembeddedprofiles false /usehtmltitleasmetadata true >> ] >> setdistillerparams << /hwresolution [2400 2400] /pagesize [612.000 792.000] >> setpagedevice powerpoint presentation methods • patients with 4-8 clinically visible ak lesions in a 25 cm2 area were randomized 1:1 to tirbanibulin ointment 1% or vehicle (5 consecutive day, once-daily self-application). • for the current analysis, data of local skin reactions (lsr) up to day (d) 57 (i.e.: erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, erosion/ulceration) in patients achieving cc (100%) with tirbanibulin were analyzed. lsrs were graded 0-3 (absent-severe). • the distribution of highest lsr grades from baseline to d57 was described by lsr. • an lsr composite score (sum of all 6 lsrs) was also calculated for each participant visit (range 0-18), and maximum composite scores were averaged for the study period. complete clearance of actinic keratosis with tirbanibulin ointment 1% is not correlated with the severity of local skin reactions synopsis • tirbanibulin is a synthetic inhibitor of tubulin polymerization and src kinase signaling. tirbanibulin ointment 1% has been approved by the fda (2020) for the treatment of actinic keratosis (ak) on the face or scalp. • of the 353 patients randomized to tirbanibulin (intention-to-treat, itt) in the phase 3 trials, 174 (49.3%) had cc in the treatment area. baseline characteristics are shown in table 1. there were no major differences between itt and patients achieving cc, except for a lower percentage of males among the latter. results 1. blauvelt a et al. new engl j med 2021;384:512-20. references • this study was funded by athenex and post-hoc analysis/medical writing was funded by almirall. • w riting support was provided by tfs healthscience. acknowledgements 2021 fall clinical dermatology conference for pas & nps brian berman1, todd schlesinger2, neal bhatia3, ayman grada4, laura padullés5, francisco hernández6, david cutler7, mark lebwohl8 1 department of dermatology and cutaneous surgery, university of miami miller school of medicine, florida, usa; 2 clinical research center of the carolinas, charleston, sc, usa; 3 therapeutics clinical research, san diego, ca, usa; 4 almirall, malvern, pa, usa; 5 almirall, barcelona, spain; 6 almirall, sant feliu de llobregat, spain; 7 athenex, inc., buffalo, ny, usa; 8 icahn school of medicine at mount sinai, new york, ny, usa bb has served as a consultant, speaker, and/or investigator for almirall, biofrontera, leo and pierre-fabre, and also participated in the us biofrontera pdt advisory council; ts has served as a consultant/speaker with honorarium, advisor and/or investigator for almirall, biofrontera, galderma, leo, ortho and sun pharmaceuticals; nb has served as a consultant with honorarium and investigator for almirall, biofrontera, leo, ortho, and sunpharma; ag, lp, fh are employees of almirall; dc is an employee of athenex; ml is an employee of mount sinai and receives research funds from: abbvie, amgen, arcutis, avotres, boehringer ingelheim, dermavant sciences, eli lilly, incyte, janssen research & development, llc, ortho dermatologics, regeneron, and ucb, inc., and is a consultant for aditum bio, almirall, altrubio inc., anaptysbio, arcutis, inc., aristea therapeutics, arrive technologies, avotres therapeutics, biomx, boehringer-ingelheim, bristol-myers squibb, cara therapeutics, castle biosciences, corrona, dermavant sciences, dr. reddy’s laboratories, evelo biosciences, evommune, inc., facilitatation of international dermatology education, forte biosciences, foundation for research and education in dermatology, helsinn therapeutics, hexima ltd., leo pharma, meiji seika pharma, mindera, pfizer, seanergy, and verrica. conflicts of interest • the highest mean (sd) composite lsr score from baseline to d57 was 4.9 (2.2) for cc patients, on a scale from 0 to 18, with 70% of patients presenting lsrs score of 5 or less. composite lsr score was ≤3 in 26.5% and ≤5 in 70.2% of cc patients (figure 2). figure 3 illustrates the evolution of ak lesions in a patient with cc and a maximum lsr composite score of 4. table 1. baseline characteristics ak, actinic keratosis; bmi, body mass index; cc, complete clearance; itt, intention-to-treat; max, maximum; min, minimum; sd, standard deviation. with cc (n=174) itt (n=353) mean (sd) age, years 68.5 (8.7) 69.3 (8.6) male, n (%) 140 (80.5) 305 (86.4) bmi (kg/m2), mean (sd) 29.0 (5.8) 28.8 (5.1) fitzpatrick skin type, n (%) type i 25 (14.4) 49 (13.9) type ii 98 (56.3) 200 (56.7) type iii 43 (24.7) 88 (24.9) type iv-vi 8 (4.6) 16 (4.5) ak lesion count, median (min-max) 5.0 (4-8) 6.0 (4-8) objective • the objective of this post-hoc pooled analysis of the two phase 3 studies is to describe the tolerability profile of tirbanibulin ointment 1% in adults with ak on face or scalp who achieved complete (100%) clearance (cc) in the treatment area (two phase 3 randomized, double-blinded, vehicle-controlled studies: nct03285477 nct03285490) table 2. highest grade of lsrs from baseline to d57 by severity among patients who achieved cc (safety population) patients with cc n (%) lsr ≤3 (n=46) overall (n=174) erythema mild 24 (52.2) 30 (17.2) moderate 22 (47.8) 128 (73.6) severe 0 (0.0) 16 (9.2) flaking/scaling mild 31 (67.4) 47 (27.0) moderate 8 (17.4) 100 (57.5) severe 0 (0.0) 19 (10.9) crusting mild 6 (13.0) 57 (32.8) moderate 0 (0.0) 32 (18.4) severe 0 (0.0) 6 (3.4) swelling mild 4 (8.7) 51 (29.3) moderate 0 (0.0) 18 (10.3) severe 0 (0.0) 2 (1.1) vesicles/pustules mild 0 (0.0) 11 (6.3) moderate 0 (0.0) 0 (0.0) severe 0 (0.0) 1 (0.6) erosions/ulcers mild 0 (0.0) 15 (8.6) moderate 0 (0.0) 4 (2.3) severe 0 (0.0) 0 (0.0) • in patients with cc, most lsrs were mild or moderate. severe reactions were reported by 0.0%-10.9% in the overall cc population and in none of the patients with lsr≤3 (table 2). no patients discontinued the study due to lsrs. lsr composite scores range from 0 (no reaction) to 18 (maximum reaction). no patients presented a highest composite score in the more severe range of 13-18. cc, complete clearance; d, day; itt, intention-to-treat; lsr, local skin reaction. figure 2. distribution of lsr composite scores from baseline to d57 among patients achieving cc cc, complete clearance; d, day; lsr, local skin reactions. figure 3. evolution of facial ak lesions in a patient achieving cc with tirbanibulin at d29 the patient was a white (fitzpatrick ii), 67 year-old male. previous dermatological conditions included facial reconstruction (1982), ak (september 2016). lsrs: d1 none; d8 flaking/scaling moderate, erythema moderate; d15 erythema moderate; d29 erythema mild; d57 none. ak, actinic keratosis; cc, complete clearance; d, day; lsr, local skin reaction. 0.0% 2.3% 9.8% 14.4% 20.7% 23.0% 10.9% 8.0% 4.0% 2.3% 2.3% 0.6% 1.7% 0% 5% 10% 15% 20% 25% 0 1 2 3 4 5 6 7 8 9 10 11 12 p e rc e n ta g e o f p a ti e n ts lsr composite score • this post-hoc analysis shows that cc of ak using tirbanibulin 1% ointment is associated with mild to moderate lsrs, with 70.2% of patients showing a composite lsr score ≤5. moreover, tirbanibulin ointment 1% showed a good efficacy/tolerability profile for most patients, being a good alternative to current treatments. conclusions acknowledgements: study funded by sol-gel technologies ltd.; poster support provided by galderma laboratories, l.p., fort worth, tx. eps.p-sgt5407-01 silica is added in 5–100 repetitive cycles to build up a silica shell around the bpo results subjects • 547 adult subjects were enrolled in the 40-week extension of the two 12-week, doubleblind, vehicle-controlled phase 3 trials (table 1). • subjects were ≥18 years old with an investigator global assessment [iga] of 3 or 4, ≥15 inflammatory lesions, and ≤2 nodules • the safety population included 535 of the 547 enrolled subjects (97.8%). all analyses were performed using the safety population • 363 subjects enrolled in the extension were previously treated with e-bpo and 184 were previously treated with vehicle during the phase 3 trials. • all subjects were assigned to treatment with e-bpo. subjects were followed for up to 40 weeks in the extension (for a total of up to 52 weeks). safety summary of treatment-emergent adverse events • most teaes were mild or moderate in severity and were not considered to be related to study treatment (table 2). summary: tolerability, safety population, baseline to week 52 • e-bpo remained well-tolerated over the course of 52 weeks • for each of the cutaneous safety and tolerability parameters, the percentage of subjects with no signs/symptoms increased from week 4 to week 52 (range 60.8% to 90.6%) • reports of severe cutaneous safety and/or tolerability evaluations included 2 subjects with dryness, 1 subject with itching, and 1 subject with burning/stinging at week 40 • there were no severe cutaneous safety evaluations at week 52 • facial erythema generally improved during the study (n=535), with a total percentage increase for subjects with none and mild erythema at week 52 and a total percentage decrease for subject with moderate and severe erythema (figure 3) encapsulated benzoyl peroxide (e-bpo): a novel formulation of bpo for long-term management of rosacea neal d. bhatia md1; edward lain md2; hilary baldwin md3,4; sam brantman pharmd5; james q. del rosso do6,7; raja k. sivamani md8,9 1therapeutics clinical research, san diego, ca; 2sanova dermatology, pflugerville, tx; 3the acne treatment & research center, brooklyn, ny; 4rutgers robert wood johnson medical center, new brunswick, nj; 5galderma laboratories, l.p., fort worth, tx; 6jdr research, las vegas, nv; 7advanced dermatology & cutaneous surgery, maitland, fl; 8integrative skin science and research, sacramento, ca; 9pacific skin institute, sacramento, ca introduction key points • bpo is a potent oxidizing agent • the utility of bpo in rosacea has been limited due to limited data on efficacy and adverse skin tolerability • a new formulation incorporating microencapsulation technology is tolerable over longterm use bpo has had a complex history in rosacea • limited data in previous studies, especially with monotherapy • effective when used in combination with clindamycin or erythromycin1,2 • while proven effective, unencapsulated bpo causes local skin irritation, including stinging, burning, and itching after application3 • demonstrated to be effective in killing demodex folliculorum4 methods study objective: • two 12-week phase 3 trials of microencapsulated benzoyl peroxide cream, 5% (e-bpo) previously demonstrated significant efficacy, rapid onset of action as early as week 2, and good safety and tolerability at week 12 • this 52-week study observed the nature, severity, and frequency of adverse events and the cutaneous safety and local tolerability of e-bpo when applied once daily (figure 1) safety endpoints: • the frequency of both local and systemic adverse events • investigator cutaneous safety assessment (dryness and scaling) and local tolerability assessment (itching and burning/stinging) at baseline and all postbaseline study visits termination: • the study was terminated early per protocol when a minimum number of patients were followed for a minimum time to adequately assess long-term safety as specified in the ich e1a guidance. summary • the cutaneous safety and local tolerability assessments demonstrated that e-bpo, when applied once daily for up to 52 weeks, was generally safe and well-tolerated • the evaluations of iga score and facial erythema showed improved clinical outcomes after 4 weeks and for up to 52 weeks of treatment with e-bpo e-bpo (n=535) any teae 185 (34.6%) any serious teae 10 (1.9%) discontinued e-bpo because of a teae 5 (0.9%) discontinued from the study because of a teae 4 (0.7%) maximum severity of teae severe 8 (1.5%) moderate 81 (15.1%) mild 96 (17.9%) relationship to study drug related 17 (3.2%) not related 168 (31.4%) *note: treatment-emergent adverse events are those events with an onset after the first application of e-bpo cream 5%. related defined as “definitely,” “probably,” or “possible.” not related defined as “unlikely” or “not related.” study terminated by sponsor 146 (26.7%) withdrawal by subject 48 (8.8%) lost to follow-up 21 (3.8%) adverse event 4 (0.7%) protocol violation 2 (0.4%) pregnancy 1 (0.2%) physician decision 1 (0.2%) other 1 (0.2%) worsening of condition 0 lack of efficacy 0 figure 2. study design figure 3. erythema at postbaseline visits, safety population figure 4. kaplan–meier analysis of time to first retreatment figure 1. encapsulation table 1. baseline demographic and clinical characteristics table 2. patient adverse event summary table 3. summary of subject completion/discontinuation drug microencapsulation background benefits of microencapsulation • creates a silicon dioxide (silica) microcapsule shell between the bpo and the skin • helps control the release rate of the drug to improve tolerability • can preserve the advantages of bpo while minimizing limitations references 1. zaenglein al, pathy al, schlosser bj, et al. guidelines of care for the management of acne vulgaris [published correction appears in j am acad dermatol. 2020;82(6):1576]. j am acad dermatol. 2016;74(5):945-973. [table v pg. 951; p. 951 col1, p3; p951 col2p2.] 2. brammann c, müller-goymann cc. int j pharm. 2020;578:119074. [pg2, col 2, para3; pg 7 table 1; pg 9 col 1 para 1; pg 9 col 2 para 4; pg 6 col 1 para 5; pg 6 col 2 para 5] 3. kolli s, pecone d, pona a, et al. topical retinoids in acne vulgaris: a systematic review. am j clin dermatol 2019;20(3):345-365. [pg 345 abstract; pg 346 col 1, para 1; pg 362, col 2 para2; pg 362 col 1 para 3col 2 para 1] 4. oztürkcan s, ermertcan at, sahin mt, afşar fs. efficiency of benzoyl peroxide-erythromycin gel in comparison with metronidazole gel in the treatment of acne rosacea. j dermatol. 2004 aug;31(8):610-7. doi: 10.1111/j.1346-8138. 5. erlich m, arie t, koifman n, et al. structure elucidation of silica-based core-shell microencapsulated drugs for topical applications by cryogenic scanning electron microscopy. j colloid interface sci. 2020 nov 1;579:778-785. doi: 10.1016/j.jcis.2020.06.114. abbreviations: e-bpo=encapsulated benzoyl peroxide; ich=international council for harmonization of technical requirements for pharmaceuticals for human use; iga=investigator global assessment; meddra=medical dictionary for regulatory activities; teae=treatment-emergent adverse event. vehicle 12 weeks 52 weeks 547 enrolled in 54-07 • 363 previously treated with e-bpo in study 1 and 2 • 184 previously treated with vehicle in study 1 and 2 e-bpo cream 5% applied e-bpo daily for up to an additional 40 weeks • subjects were on treatment only when iga >1 study 1 and 2 sgt 54-07 pe rc en ta ge o f p at ie nt s (% ) none baseline week 4 week 8 week 12 week 16 week 20 week 24 week 28 week 32 week 36 week 40 week 44 week 48 week 52 mild treatment week moderate severe 0 25 50 75 100 baseline = 0.4% week 52 = 11% baseline = 14.4% week 52 = 0.5% baseline = 9.7% week 52 = 70.3% baseline = 75.5% week 52 = 18.2% pe rc en t o f p at ie nt s w ith ou t r el ap se • mean of 1.4 retreatments • median number of treatment-free days was 58 for patients with a score of 0 at the beginning of the extension, the mean time to first retreatment was 125.1 days 0 10 20 30 40 50 60 70 80 90 100 100 110 120 130 140 150 160 170 180 190 200 210 220 230 240 250 260 280 290 treatment-free days until first retreatment 0 10 30 20 40 50 100 90 80 70 60 censored a multicenter, open-label, long-term safety study of e-bpo to evaluate the safety of e-bpo in patients with papulopustular rosacea all enrolled subjects, n=547, 59% (n=323) completed the study, and 41% (n=224) did not complete. see table 3. e-bpo provided a sustained effect in rosacea patients for over 1 year (52 weeks) vehicle in phase 3 trials (n=172) e-bpo cream, 5% in phase 3 trials (n=363) all patients (n=535) age (years) mean (sd) 52.0 (12.75) 51.3 (13.88) 51.5 (13.52) median 53 (22-81) 52.0 (19-81) 53.0 (19-81) sex male 52 (30.2%) 101 (27.8%) 153 (28.6%) female 120 (69.8%) 262 (72.2%) 382 (71.4%) inflammatory lesion count mean (sd) 27.6 (12.83) 28.8 (13.24) 28.4 (13.11) median 23.0 (15-70) 24.0 (15-70) 24.0 (15-70) iga 3 moderate 157 (91.3%) 320 (88.2%) 477 (89.2%) 4severe 15 (8.7%) 43 (11.8%) 58 (10.8%) censored = subjects who discontinued the ltss while not being treated and had not yet previously relapsed were considered censored in the kaplan–meier analysis. skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 579 in-depth review melanoma recurrence after mohs micrographic surgery with mart-1: a systematic review and meta-analysis tyler long, do1*, austin dunn, do2, mary arndt, ms3, eric parlette, md1 1 hca healthcare lewisgale hospital-montgomery, blacksburg, va 2 center for clinical and cosmetic research, aventura, fl 3 lake erie college of osteopathic medicine, bradenton, fl cutaneous melanoma (cm) affects about 287,000 people each year, worldwide.1 worse prognoses are associated with cm located on the head, neck, and trunk compared to extremities with the exception of acral melanoma.2 surgical management continues to be the primary therapeutic approach for cm.3 current surgical recommendations for primary cm include surgical excision with pre-determined surgical margins based on tumor characteristics and subsequent microscopic margin assessment as needed. wide local excision (wle) continues to be the primary recommendation of the american academy of dermatology (aad), with margins predicated by tumor depth.3 extra consideration must be made for anatomically constrained sites and/or when subclinical spread is suspected. mohs micrographic surgery (mms) is recommended to treat primary melanoma in situ and lentigo maligna located on the head and neck, acral sites, genitalia, and pretibial leg, and for locally recurrent melanoma in situ lentigo maligna in any location.4 the 2019 aad workgroup has encouraged further study of mms on these anatomically constrained areas. mohs micrographic surgery offers particular advantages for tumors located in areas that require tissue conservation and when subclinical spread is suspected. mms is ideal for the head and neck due to the high abstract background: surveys suggest wide-spread use of mart-1 in mms for cm among mohs surgeons, but no previous systematic review has investigated the efficacy of this specific procedure. methods: a systematic search and meta-analysis of retrospective studies on mms with mart-1 was performed from pubmed, medline, and cochrane databases for articles published from their inception to october 30, 2020. we performed a chi-squared analysis of homogenized data to examine the relationship between recurrence location and rate of recurrence. a risk of bias was obtained with the robins-i tool. [prospero id: crd42020221826] results: among the included studies, there were a total of 15 (0.52%) local recurrences of melanoma in-situ and invasive melanoma after mms with mart-1. conclusions: this review has served to demonstrate that mms with mart-1 immunostaining in frozen sections is a technique that produces satisfactory recurrence rates for melanoma in-situ and invasive melanoma. introduction https://paperpile.com/c/pfl6yn/je3oj https://paperpile.com/c/pfl6yn/6lmhh https://paperpile.com/c/pfl6yn/fnfpv https://paperpile.com/c/pfl6yn/fnfpv https://paperpile.com/c/pfl6yn/ozwxd skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 580 recurrence rates of cm due to particular risk features, such as, subclinical spread, larger preoperative size, more likely to have had previous treatment, and requiring tissuerearranging reconstruction when compared to keratinocytic tumors.5 immediate margin assessment provides the confidence of complete tumor removal. unfortunately, hematoxylin and eosin frozen sections are notoriously difficult to interpret for cm, resulting in poor sensitivity and specificity.6– 12 over the years, immediate margin assessment has evolved to a more specific analysis. the utilization of immunostains, such as melanoma-associated antigen recognized by t-cells (mart-1), has improved the confidence in and histologic accuracy of mms in some subtypes of cm.13–15 this is most evident in melanocytic lesions demonstrating extensive subclinical spread.14–21 furthermore, mart-1 staining of frozen sections has become more rapid and as reliable as permanent sections.13,22 a recent survey of mohs surgeons and database analysis suggests wide-spread use of mart-1 in mms for cm.23,24 with techniques in mms for treating melanocytic lesions evolving, there is an impetus to continue to evaluate emerging research for further clinical guideline development. to date, no systematic reviews have specifically examined the utilization of mart-1 staining in frozen sections for cm – particularly its effect on local recurrence. sharma and colleagues25 performed a broad systematic review to compare the local recurrence of mms with that of traditional surgical techniques for lentigo maligna/lentigo maligna melanoma (lm/lmm) but only included 2 studies and failed to compare with mart-1. in this study, the authors aim to systematically review and analyze the rate of local recurrence after utilization of mohs micrographic surgery with mart-1 immunohistochemistry in frozen sections in patients being treated for primary and recurrent cutaneous melanoma. the increasing utilization of mart-1 staining in mms supports the further evaluation of the practice. the authors followed the guidelines of the cochrane handbook for systematic reviews of interventions to execute the study. the authors followed the prisma (preferred reporting items for systematic reviews and meta-analyses) statement and checklist to publish and report this metaanalysis. the protocol was determined before the search and data extraction took place. [prospero id: crd42020221826] search strategy the authors conducted a systematic search with pubmed, medline, and cochrane databases for articles published from their inception to october 30, 2020, to identify relevant studies published in english. electronic searches were performed with the following search terms: ["mohs" and "melanoma"]. the clinicaltrials.gov database was searched for current trials. the authors manually checked the bibliographies of the identified articles, including any relevant reviews or metaanalyses to further identify eligible studies. eligibility criteria the inclusion criteria are (1) utilization of mart-1 immunohistochemistry in frozen sections, (2) melanoma in situ or invasive melanoma, (3) prospective, (4) retrospective, (5) randomized controlled trials (6) published in a peer-reviewed methods https://paperpile.com/c/pfl6yn/qu119 https://paperpile.com/c/pfl6yn/oju53+w5tzs+kul3t+ihbi4+imoa9+mcfb9+pgwh7 https://paperpile.com/c/pfl6yn/oju53+w5tzs+kul3t+ihbi4+imoa9+mcfb9+pgwh7 https://paperpile.com/c/pfl6yn/sdno1+far1q+espgw https://paperpile.com/c/pfl6yn/far1q+espgw+gl1su+elted+islsn+uciep+hiycb+4aeko https://paperpile.com/c/pfl6yn/sdno1+jlusn https://paperpile.com/c/pfl6yn/x8lwb+matsa https://paperpile.com/c/pfl6yn/z11r1 skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 581 journal, (7) published in english, (8) and fulltext of the studies available. the exclusion criteria are (1) digital melanoma, (2) “how we do it” articles, (3) review studies (4), and basic science studies. data extraction and outcomes all relevant information regarding study characteristics design, level of evidence, the methodological quality of evidence, population, outcome measures, and followup time points were collected by two independent reviewers using a predetermined datasheet. two independent reviewers oversaw all review process steps, and data were independently obtained and their inclusion criteria agreed upon. any disagreement over data relevancy were settled by a third reviewer. the primary extracted outcome was local recurrence rates. quality assessment patient characteristics and control protocols were reviewed to evaluate for possible confounding variables. the risk-of-bias (rob) plot was created using the cochrane risk of bias in non-randomized studies of interventions (robins-i) tool. rob judgments were made following the supplementary guidance of sterne et. al.26 data analysis the number of local recurrences was homogenized by determining the percent affected. a χ² test of independence was performed to examine the relationship between recurrence location and rate of recurrence. a comparison of proportions was utilized to analyze demographic data. a p-value <0.05 was considered statistically significant, and 95% confidence intervals (cis) were reported. literature search the literature search identified 617 total manuscripts. once articles were screened for inclusion and exclusion criteria, 17 fulltext articles were assessed for eligibility (figure 1). four manuscripts with a total of 2,896 lesions were included in the review.17,18,27,28 nine manuscripts were excluded due to the lack of recurrence rates.4,13–16,20,29–31 single manuscripts were excluded due to the lesion type32, modified procedures19, digital melanoma33, or inclusion of the same data set.21 clinicaltrials.gov did not provide any additional information concerning on-going research on this subject. study characteristics all four included studies, summarized in table 1, were retrospective. there were 492 invasive melanomas (im) and 2,404 melanoma in-situ (mis), of which 2,556 were primary lesions. of the included lesions, 1,724 were located on the head/neck and 1,172 were located on the trunk/extremities. the outcomes utilized in the included studies were local recurrence, rate of metastasis, overall survival, disease-free survival rates, upstaging of the lesion, and/or surgical margins required for complete removal. mean follow-up periods ranged from 1,026 to 1,361 days, with a reported minimum and maximum of 3 and 3167 days, respectively. demographics age was reported as a mean with a range in all of the included studies. there was no report of standard deviation. the ages of the results https://paperpile.com/c/pfl6yn/av3o https://paperpile.com/c/pfl6yn/elted+islsn+dpatw+ds0a7 https://paperpile.com/c/pfl6yn/ozwxd+sdno1+far1q+espgw+gl1su+hiycb+3mn6c+abpm0+7toby https://paperpile.com/c/pfl6yn/ilbcj https://paperpile.com/c/pfl6yn/uciep https://paperpile.com/c/pfl6yn/4s0gi https://paperpile.com/c/pfl6yn/4aeko skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 582 patients in this review ranged from 12 to 99. the average age of participants was 66 in three of the four included studies, and not reported in the last. sex demographics were reported in all of the included studies. a (chi-squared test) significant majority of the participants were male, with a total of 61.5% [p < 0.0001]. the location of the lesions was reported in all of the included studies. while some studies were more specific with particular locations, all of them included head, neck, trunk, and limbs. in total, 1,724 melanomas were on the head and neck; 1,172 were elsewhere (table 1). tumor specifics included whether or not the lesion was primary or recurrent and invasive or in-situ. the average breslow depth of invasive melanomas was also included. there were 2,556 (88%) primary melanomas. of these melanomas, 2,404 (83%) were mis. the average breslow depth (of im) was estimated to be 0.768mm with a range of 0.1–5.8mm. two studies did not report the range of depth, and one did not provide an average depth. methodology all of the included studies were retrospective cohort studies that gathered data from their respective institutions only. the mms technique described varied slightly. two of the studies report utilizing a central debulking excision for bread-loafing in permanent paraffin-embedded h&e for the staging of the melanoma.17,28 the remaining studies either did not report such a technique or were vague about their technique, merely referring to previous reports. two studies described an initial debulking margin of 2–3mm with an additional 2–3mm mohs margin that was subsequently utilized for frozen sections.17,28 degesys et al. reported an initial 5mm margin with 3mm subsequent mohs margins.27 valentin et al. did not report the specific margins utilized.18 positive margin determination was relatively homogenous across the studies. they all utilized, at a minimum, the following: pagetoid spread, nests of at least 3 atypical melanocytes, and confluent melanocyte hyperplasia along the basement membrane. follow-up data was collected similarly across the included studies. with the exception of one, all of the included studies utilized over-the-phone screening of the participants. local recurrence among the included studies, there were 15 (0.52%) local recurrences of melanoma in situ and invasive melanoma after mms with mart-1. the descriptions of each recurrence can be found in table 2. mis did not convert to im in any of the reported recurrences. in primary vs recurrent melanomas (im and mis), x2 (1, n = 2,894) = 3.26, p = .071, the chance of recurrence was not significantly different. by contrast, the chance of recurrence was significantly higher in invasive melanoma when compared to melanoma in situ: x2 (1, n = 2,896) = 19.76, p < .001. there was no significant difference in cm recurrence between the two general locations of “head/neck” and “other location”: x2 (1, n = 2,896) = 2.65, p = 0.10. notably, all “other location” recurrences were on the feet; no recurrences were observed on the proximal extremities. of the head and neck melanomas, most local recurrence (1.99%) occurred on the scalp. all were initially invasive melanomas. risk of bias https://paperpile.com/c/pfl6yn/elted+ds0a7 https://paperpile.com/c/pfl6yn/elted+ds0a7 https://paperpile.com/c/pfl6yn/dpatw https://paperpile.com/c/pfl6yn/islsn skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 583 the review authors judged that three studies had a moderate rob and the final study had a low rob (figure 2). all of the included studies were able to measure important known confounding domains, such as, patient age, patient sex, tumor location, breslow depth, primary and recurrent lesions, and lesion type. the cohort research design without the use of control groups suggests that the effect of confounding variables within the treatment groups is unlikely. bias in the selection of participants into the study was moderate for degesys et. al.27 due to risk of recall bias in 6-month telephone follow-up. foxton et. al.17 figure 1. prisma flow-chart aimp; atypical intraepidermal melanocytic proliferation https://paperpile.com/c/pfl6yn/dpatw https://paperpile.com/c/pfl6yn/elted skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 584 figure 2. risk of bias analysis provided no information about the selection of participants or the database they used. degesys et. al. lost 13.9% of patients to follow up and valentin et. al. lost 24.2% of patients to follow up and were considered to have a moderate risk of bias due to missing data. mms with mart-1 demonstrates lower recurrence rates than conventional excision or mms without mart-1.34 of the included studies, the rate of recurrence of mis after mms with mart-1 was just 0.25% (6/2404). according to the work of nosrati et. al., if the mart-1 stain is not used with mms, the recurrence rate increases to 1.8% (5/277). the recurrence rate of mis after wle has been reported to be as high as 5.7% (22/395).35 the utilization of mart-1 in mms for cm demonstrates advantages over classical mms in recurrence27,36 and in surgeon preference. the transition to mart-1 from h&e alone and/or hmb-45 took place in many important retrospective studies.14,20,21,33,36,37 this transition appeared to occur around 2002, when further investigation suggested mart-1 was the superior immunohistochemistry stain in frozen sections due to reliable epidermal staining, ease of interpretation, and highest histopathologic concordance.14,15,38–41 subsequently, studies began to demonstrate improved recurrence rates after transitioning to exclusively using mart-1.21,33,36 in a recent study by burnett et al.,37 a retrospective analysis of im on the trunk and proximal extremities treated by mms observed only 2 (0.14%) recurrences. the authors established that the sample included procedures that utilized h&e alone, then discussion https://paperpile.com/c/pfl6yn/jnljv https://paperpile.com/c/pfl6yn/af2r5 https://paperpile.com/c/pfl6yn/dpatw+baigu https://paperpile.com/c/pfl6yn/vbvo4+baigu+4s0gi+4aeko+hiycb+far1q https://paperpile.com/c/pfl6yn/far1q+espgw+l0ufs+v8oqc+jwq96+tpngj https://paperpile.com/c/pfl6yn/baigu+4s0gi+4aeko https://paperpile.com/c/pfl6yn/vbvo4 skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 585 hmb, then mart-1 exclusively. recurrences occurred only prior to the incorporation of mart-1 immunostaining in mms. while the sample included in this study was much larger than the invasive melanoma collective sample in the present study, it corroborates an extremely low recurrence rate when mart-1 is utilized for im for the trunk and proximal extremities. from 2001 to 2016, the chances of receiving mms for melanoma increased 304%. twenty-seven percent of the mms cases reported use of immunohistochemistry stains (ihc), with an increase in utilization over recent years with further acceptance of its benefit.24 in addition to ease of use/interpretability and outcome improvement, it is important to investigate financial feasibility. wilson et al. demonstrated that among comprehensive margin assessment techniques for mis/im, staged excision using en-face margin assessment (seem) and mms with mart-1 were similar in cost for the healthcare system. the authors noted that seem incurred lower costs due to decreased excision code reimbursement and lower number of stages, while mms with mart-1 required less complex reconstruction and the multiple procedure reduction rule. mms “classic” with h&e generally required more stages, larger margins, and a flap or graft.31 recent epidemiological research suggests that there are no significant differences in local recurrence or overall survival when comparing mms and wle for head, neck, trunk, and extremities.42–44 conversely, valentin et al. provides 5-year kaplan-meier local recurrence rates for primary cm treated with mms with mart-1 that are significantly lower than historical controls of conventional wide-local excision.18 we feel that these discordances may have occurred due to lack of considering specific mm table 1: study characteristics foxton degesys etzkorn valentin total n 62 123 597 2,114 2896 age, mean (range) 63.2 (34-88) 66.48 (1794) 66 (18-93) 66 (12-99) sex female 33 (53.2%) 45 (36.6%) 226 (37.9%) 810 (38.3%) 1114 38.50% p < 0.0001 male 29 (46.8%) 78 (63.4%) 371 (62.1%) 1304 (61.7%) 1782 61.50% lesion type lr lr% primary 58 (93.5) 117 (95.1) 499 (83.6) 1882 (89.1) 2556 11 0.43% p = 0.0710 recurrent 4 (6.5) 6 (4.9) 98 (16.4) 230 (10.9) 338 4 1.18% lr lr% im 8 (12.9) 123 (100) 161 (27) 200 (9.5) 492 9 1.83% p < 0.0001 desmoplastic nr nr 8 nr mis 54 (87.1) 0 436 (73) 1,914 (90.5) 2404 6 0.25% location lr lr% other location 7 (11.3) 53 (43.1) 122 990 1172 3 0.25% p = 0.1035 head/neck, total 55 (88.7) 70 (56.9) 475 (79.4) 1124 (53.2) 1724 12 0.69% face 49 47 (38.2) 355 (74.7) 944 (44.7) 1395 9 0.64% neck 3 11 (8.9) 26 (5.5) 82 (3.9) 122 0 0 scalp 3 5 (4.1) 45 (9.5) 98 (4.6) 151 3 1.99% ears nr 7 (5.7) 49 (10.3) nr 56 0 0 local recurrence data mean f/u time (3-30 mo) 1273 days 1026 days 3.73 years lr, total 0 2 (1.63%) 2 (0.34%) 11 (0.52%) lr; local recurrence. nr; not reported. mis; melanoma in-situ. im; invasive melanoma. f/u; follow-up. mo; months. https://paperpile.com/c/pfl6yn/matsa https://paperpile.com/c/pfl6yn/7toby https://paperpile.com/c/pfl6yn/flnik+dwqcw+t51cn https://paperpile.com/c/pfl6yn/islsn skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 586 table 2: description of recurrences location type initial recurrence days to recur cheek 2 im im ~328 nr im im 1984 nose 1 im mis ~97 2 im im ~708 scalp 1 im im ~876 1 im mis ~1938 1 im im ~2084 foot nr im im 489 2 im im ~774 location type initial recurrence days to recur cheek 1 mis mis ~98 nr mis mis 154 1 mis mis ~215 1 mis mis ~2307 nose 1 mis mis ~376 foot nr mis mis 1484 nr; not reported. im; invasive melanoma. mis; melanoma in-situ. 1; primary. 2; secondary techniques as a confounding variable in epidemiological studies. the data presented in this study demonstrates that the increasing utilization of mart-1 in mms for cutaneous melanoma is warranted and should be recommended, where applicable. the evidence supports current auc3 and nccn45 recommendations while evidence suggests further use of mms with mart-1 for cm where local excision continues to demonstrate worse recurrence rates. mms with mart-1 has demonstrated strong evidence to support its routine use for invasive melanoma at “special sites” (head, neck, acral sites, genitalia, and pretibial leg) and on the trunk/proximal extremities. the limitations of this review and the included studies are inherent and technical. the primary limitation of the included studies is that they were all observational studies that were retrospective in nature. a limitation of the review was the exclusion of alternative surgical techniques utilizing mart-1, such as modified staged-excision. furthermore, there may be a serious confounding variability in surgical technique, frozen section technique, and mart-1 interpretation skill. lastly, this review did not differentiate the lentigo maligna and melanoma in situ as separate entities and were all treated as mis. this review demonstrates that the technique of mms with mart-1 ihc in frozen sections produces satisfactory recurrence rates for melanoma in situ and invasive melanoma. there appears to be discordance between current guidelines and research supporting broader use of mms with mart-1. further prospective research should be done to evaluate clinical outcomes with the use of mms for invasive and noninvasive cm in various body locations. conflict of interest disclosures: none funding: none corresponding author: tyler long, do dermatology resident river ridge dermatology hca healthcare lewisgale hospital-montgomery phone: 540-520-6082 conclusion https://paperpile.com/c/pfl6yn/fnfpv https://paperpile.com/c/pfl6yn/ftq1f skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 587 email: tyler.long@hcahealthcare.com references: 1. ferlay, j. et al. estimating the global cancer incidence and mortality in 2018: globocan sources and methods. int. j. cancer 144, 1941– 1953 (2019). 2. balch, c. m. cutaneous melanoma: prognosis and treatment results worldwide. semin. surg. oncol. 8, 400–414 (1992). 3. swetter, s. m. et al. guidelines of care for the management of primary cutaneous melanoma. j. am. acad. dermatol. 80, 208–250 (2019). 4. etzkorn, j. r. et al. correlation between appropriate use criteria and the frequency of subclinical spread or reconstruction with a flap or graft for melanomas treated with mohs surgery with melanoma antigen recognized by t cells 1 immunostaining. dermatol. surg. 42, 471–476 (2016). 5. fix, w. et al. melanomas of the head and neck have high-local recurrence risk features and require tissue-rearranging reconstruction more commonly than 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review. dermatol. surg. 46, 1004–1013 (2020). 20. kunishige, j. h., doan, l., brodland, d. g. & zitelli, j. a. comparison of surgical margins for lentigo maligna versus melanoma in situ. j. am. acad. dermatol. 81, 204–212 (2019). 21. stigall, l. e., brodland, d. g. & zitelli, j. a. the use of mohs micrographic surgery (mms) for melanoma in situ (mis) of the trunk and proximal extremities. j. am. acad. dermatol. 75, 1015–1021 (2016). 22. cherpelis, b. s., moore, r., ladd, s., chen, r. & glass, l. f. comparison of mart-1 frozen sections to permanent sections using a rapid http://paperpile.com/b/pfl6yn/je3oj http://paperpile.com/b/pfl6yn/je3oj http://paperpile.com/b/pfl6yn/je3oj http://paperpile.com/b/pfl6yn/je3oj http://paperpile.com/b/pfl6yn/je3oj http://paperpile.com/b/pfl6yn/je3oj http://paperpile.com/b/pfl6yn/je3oj http://paperpile.com/b/pfl6yn/je3oj http://paperpile.com/b/pfl6yn/je3oj http://paperpile.com/b/pfl6yn/je3oj http://paperpile.com/b/pfl6yn/6lmhh 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http://paperpile.com/b/pfl6yn/v8oqc http://paperpile.com/b/pfl6yn/v8oqc http://paperpile.com/b/pfl6yn/v8oqc http://paperpile.com/b/pfl6yn/jwq96 http://paperpile.com/b/pfl6yn/jwq96 http://paperpile.com/b/pfl6yn/jwq96 http://paperpile.com/b/pfl6yn/jwq96 http://paperpile.com/b/pfl6yn/jwq96 http://paperpile.com/b/pfl6yn/jwq96 http://paperpile.com/b/pfl6yn/jwq96 http://paperpile.com/b/pfl6yn/jwq96 http://dx.doi.org/10.1016/j.jaad.2017.11.055 http://paperpile.com/b/pfl6yn/jwq96 http://paperpile.com/b/pfl6yn/tpngj http://paperpile.com/b/pfl6yn/tpngj http://paperpile.com/b/pfl6yn/tpngj http://paperpile.com/b/pfl6yn/tpngj http://paperpile.com/b/pfl6yn/tpngj http://paperpile.com/b/pfl6yn/tpngj http://paperpile.com/b/pfl6yn/tpngj http://paperpile.com/b/pfl6yn/tpngj http://paperpile.com/b/pfl6yn/flnik http://paperpile.com/b/pfl6yn/flnik http://paperpile.com/b/pfl6yn/flnik http://paperpile.com/b/pfl6yn/flnik http://paperpile.com/b/pfl6yn/flnik http://paperpile.com/b/pfl6yn/flnik 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http://paperpile.com/b/pfl6yn/ftq1f skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 589 summary presented at the 42nd annual fall clinical dermatology conference | las vegas, nv | october 20–23, 2022 objectives to report long-term safety data, pooled to include three years of treatment, in patients with moderate to severe plaque psoriasis treated with bimekizumab (bkz) across four phase 2 and four phase 3 clinical trials. introduction • bkz is a monoclonal immunoglobulin g1 antibody which selectively inhibits interleukin (il)-17f in addition to il-17a,1,2 and is used in the treatment of psoriasis. • given the chronic nature of psoriasis, it is important to consider long-term safety of treatments.3 • data pooled over two years have indicated that bkz is generally well-tolerated.4 • here, the first three-year safety data for bkz in patients with moderate to severe plaque psoriasis are reported, pooled from phase 2 and 3 clinical trials. materials and methods • long-term safety data were evaluated for all patients who received ≥1 dose of bkz in four phase 3 trials (be sure, be vivid, be ready, and their ongoing open-label extension be bright [data cut-off: 23 oct 2021]) and four phase 2 trials (be able 1, be able 2, ps0016, and ps0018).5 • safety data were also evaluated separately for patients receiving bkz dosed 320 mg every 4 weeks (q4w) or every 8 weeks (q8w); q8w dosing was only used in maintenance treatment in phase 3 trials, however, most patients were receiving bkz q8w by year 3. • treatment-emergent adverse events (teaes) were coded using meddra v19.0. data are presented cumulatively as exposure-adjusted incidence rates (eairs), defined as the incidence of new cases per 100 patient-years (py). results • baseline demographics were similar between bkz dose groups (table 1). • safety data observed over three years of bkz treatment were consistent with those observed over two years;4 eairs did not increase with longer bkz exposure, and were generally lower in q8wvs q4w-treated patients (figure 1, table 2). • the three most common teaes in the phase 2/3 trials with bkz were nasopharyngitis, oral candidiasis, and upper respiratory tract infection, consistent with previous reports (table 2).4 • eighteen deaths occurred; all were deemed unrelated to bkz except one (relationship unknown) at the time of the data cut-off. • the rates of inflammatory bowel disease, adjudicated major adverse cardiac events, malignancies, adjudicated suicidal ideation and behavior, and neutropenia remained low, and were comparable to two-year data (table 2).4 there were no cases of active tuberculosis. • rates of oral candidiasis decreased with longer duration of bimekizumab exposure (figure 1c; table 2). no serious oral candidiasis events occurred; the vast majority were mild or moderate (99.4%). over three years of bkz treatment, 79.9% of patients experienced no oral candidiasis events. of those who did experience such events, most had either one (9.8%) or two (5.1%) occurrences. conclusions bkz was well-tolerated over three years of treatment; no safety signals were identified. eairs of teaes did not increase compared with data from two years of treatment.4 kenneth b. gordon,1 richard g. langley,2 richard b. warren,3 yukari okubo,4 david rosmarin,5 mark lebwohl,6 luke peterson,7 cynthia madden,7 dirk de cuyper,8 natalie nunez gomez,9 diamant thaçi10 bimekizumab safety in patients with moderate to severe plaque psoriasis: analysis of pooled data from up to three years of treatment in phase 2 and 3 clinical trials previously presented at eadv 2022 institutions: 1medical college of wisconsin, milwaukee, wisconsin, usa; 2dalhousie university, halifax, nova scotia, canada; 3dermatology centre, salford royal nhs foundation trust, manchester nihr biomedical research centre, the university of manchester, manchester, uk; 4tokyo medical university, tokyo, japan; 5department of dermatology, tufts medical center, boston, massachusetts, usa; 6icahn school of medicine at mount sinai, new york, new york, usa; 7ucb pharma, raleigh, north carolina, usa; 8ucb pharma, brussels, belgium; 9ucb pharma, monheim, germany; 10institute and comprehensive center for inflammation medicine, university of lübeck, lübeck, germany. references: 1glatt s et al. ann rheum dis 2018;77:523–32; 2adams r et al. front immunol 2020;11:1894; 3warren rb et al. j invest dermatol 2015;135:2632–40; 4gordon kb et al. jama dermatol 2022;158(7):735–744; 5be sure (nct03412747); be vivid (nct03370133); be ready (nct03410992); be bright (nct03598790); be able 1 (nct02905006); be able 2 (nct03010527); ps0016 (nct03025542); ps0018 (nct03230292). author contributions: substantial contributions to study conception/design, or acquisition/analysis/interpretation of data: kbg, rgl, rbw, yo, dr, ml, lp, cm, ddc, nng, dt; drafting of the publication, or revising it critically for important intellectual content: kbg, rgl, rbw, yo, dr, ml, lp, cm, ddc, nng, dt; final approval of the publication: kbg, rgl, rbw, yo, dr, ml, lp, cm, ddc, nng, dt. author disclosures: kbg: received consulting fees from abbvie, almirall, amgen, boehringer ingelheim, bristol myers squibb, celgene, dermira, eli lilly, janssen, novartis, pfizer, sun pharma, and ucb pharma; research support from abbvie, bristol myers squibb, celgene, eli lilly, janssen, novartis, and ucb pharma. rgl: principal investigator for abbvie, amgen, boehringer ingelheim, celgene, eli lilly, leo pharma, merck, novartis, pfizer, ucb pharma; served on scientific advisory boards for abbvie, amgen, boehringer ingelheim, celgene, eli lilly, leo pharma, merck, novartis, pfizer, ucb pharma; provided lectures for abbvie, amgen, celgene, eli lilly, leo pharma, merck, novartis, and pfizer. rbw: received consulting fees from abbvie, almirall, amgen, arena, astellas, avillion, biogen, boehringer ingelheim, bristol myers squibb, celgene, eli lilly, gsk, janssen, leo pharma, novartis, pfizer, sanofi, and ucb pharma; received research grants to institution from abbvie, almirall, janssen, leo pharma, novartis, and ucb pharma; honoraria from astellas, dice, gsk, and union. yo: received research grants from eisai, maruho, shiseido, torii; current consulting/advisory board agreements from abbvie, amgen, boehringer ingelheim, bristol myers squibb, eli lilly, janssen, sun pharma; speakers bureau from abbvie, amgen, boehringer ingelheim, bristol myers squibb, celgene, eisai, eli lilly, janssen, jimro, kyowa kirin, leo pharma, maruho, novartis, pfizer, sanofi, sun pharma, taiho, tanabe-mitsubishi, torii, ucb pharma; clinical trials sponsored by abbvie, amgen, boehringer ingelheim, bristol myers squibb, celgene, eli lilly, janssen, leo pharma, maruho, pfizer, sun pharma, and ucb pharma. dr: received honoraria as a consultant for abbvie, abcuro, altrubio, boehringer ingelheim, bristol myers squibb, celgene, concert, dermavant, dermira, eli lilly, incyte, janssen, kyowa kirin, novartis, pfizer, regeneron, sanofi, sun pharma, ucb pharma, vielabio; has received research support from abbvie, amgen, bristol myers squibb, cara therapeutics, celgene, dermira, eli lilly, galderma, incyte, janssen, merck, novartis, pfizer, and regeneron; served as a paid speaker for abbvie, amgen, celgene, eli lilly, janssen, novartis, pfizer, regeneron, and sanofi. ml: employee of mount sinai; receives research funds from abbvie, amgen, arcutis, avotres therapeutics, boehringer ingelheim, cara therapeutics for yo, dermavant, eli lilly, incyte, janssen, ortho dermatologics, regeneron, and ucb pharma; consultant for aditum bio, almirall, altrubio, anaptysbio, arcutis, aristea therapeutics, arrive technologies, avotres therapeutics, biomx, boehringer ingelheim, bristol myers squibb, cara therapeutics, castle biosciences, corevitas (formerly corrona), dermavant, dr. reddy’s laboratories, evelo biosciences, evommune, facilitation of international dermatology education, forte biosciences, foundation for research and education in dermatology, helsinn therapeutics, hexima, leo pharma, meiji seika pharma, mindera, pfizer, samsung, seanergy, and verrica. lp, cm, ddc: employees and shareholders of ucb pharma. nng: former employee and shareholder of ucb pharma. dt: honoraria for participation on advisory boards, as a speaker and for consultancy from abbvie, almirall, amgen, biogen, boehringer ingelheim, bristol myers squibb, celltrion, eli lilly, galapagos, janssen, leo pharma, novartis, pfizer, regeneron, sanofi genzyme, sun pharma and ucb pharma; received research grants received from leo pharma and novartis. acknowledgements: this study was funded by ucb pharma. we thank the patients and their caregivers in addition to the investigators and their teams who contributed to this study. the authors acknowledge susanne wiegratz, msc, ucb pharma, monheim, germany for publication coordination, emma francis-gregory, ba, costello medical, cambridge, uk, for medical writing and editorial assistance and the design team at costello medical for graphic design assistance. rbw is supported by the nihr manchester biomedical science centre. all costs associated with development of this poster were funded by ucb pharma. table 1 baseline characteristics table 2 summary of treatment exposure, summary of teaes, most common teaes, and teaes of interest in bkz-treated patients in the phase 2 and 3 trials alt: alanine aminotransferase; ast: aspartate aminotransferase; bkz: bimekizumab; ci: confidence interval; eair: exposure-adjusted incidence rate; il-17: interleukin-17; mace: major adverse cardiac event; nmsc: non-melanoma skin cancer; ole: open-label extension; py: patient-years; q4w: every 4 weeks; q8w: every 8 weeks; sd: standard deviation; sib: suicidal ideation and behavior; teae: treatment-emergent adverse event; tnf: tumour necrosis factor; uln: upper limit of normal. figure 1 cumulative eairs for teaes over three years in the phase 2 and 3 trials apatients who received both bkz 320 mg q4w and q8w are included in the population count of both treatment groups, but only once in each bkz total group. phase 2 and 3 phase 3 bkz totala (n=1,789) bkz 320 mg q4w (n=1,456) bkz 320 mg q8w (n=1,289) bkz totala (n=1,495) age (years), mean ± sd 45.2 ± 13.5 45.4 ± 13.5 45.5 ± 13.3 45.4 ± 13.4 male, n (%) 1,252 (70.0) 1,042 (71.6) 934 (72.5) 1,067 (71.4) caucasian, n (%) 1,468 (82.1) 1,173 (80.6) 1,057 (82.0) 1,208 (80.8) region, n (%) north america 635 (35.5) 534 (36.7) 432 (33.5) 542 (36.3) central/eastern europe 728 (40.7) 535 (36.7) 528 (41.0) 558 (37.3) western europe 168 (9.4) 164 (11.3) 144 (11.2) 168 (11.2) asia/australia 258 (14.4) 223 (15.3) 185 (14.4) 227 (15.2) weight (kg), mean ± sd 89.0 ± 22.0 89.1 ± 22.3 89.0 ± 21.7 89.1 ± 22.3 disease duration (years), mean ± sd 17.7 ± 12.3 17.8 ± 12.3 18.3 ± 12.4 17.9 ± 12.3 prior biologic therapy, n (%) 636 (35.6) 559 (38.4) 508 (39.4) 576 (38.5) anti-tnf 240 (13.4) 200 (13.7) 180 (14.0) 207 (13.8) anti-il-17 343 (19.2) 331 (22.7) 312 (24.2) 343 (22.9) prior systemic therapy, n (%) 1,360 (76.0) 1,135 (78.0) 1,019 (79.1) 1,166 (78.0) teaes over two years4 teaes over three years phase 2 and 3 phase 2 and 3 phase 3 bkz totala (n=1,789) bkz totala (n=1,789) bkz 320 mg q4w (n=1,456) bkz 320 mg q8w (n=1,289) bkz totala (n=1,495) summary of treatment exposure total exposure, py 3,109.7 4,245.3 1,965.6 1,914.5 3,876.4 mean exposure ± sd, days 608.5 ± 232.6 837.0 ± 365.7 476.2 ± 284.4 536.5 ± 290.8 932.4 ± 317.7 median exposure (range), days 673.0 (1–1,037) 995.0 (1–1,326) 504.0 (23–1,093) 448.0 (1–1,214) 1,058.0 (23–1,326) summary of teaes, eair/100 py (95% ci) any teae 202.4 (192.6, 212.6) 186.1 (177.2, 195.3) 217.9 (205.8, 230.5) 115.6 (108.2, 123.3) 175.5 (166.4, 185.0) severe teaes 5.4 (4.6, 6.3) 4.9 (4.3, 5.6) 5.3 (4.3, 6.4) 4.2 (3.3, 5.2) 4.5 (3.9, 5.3) teaes leading to discontinuation 3.8 (3.1, 4.6) 3.5 (3.0, 4.1) 3.8 (2.9, 4.7) 2.5 (1.9, 3.3) 3.2 (2.6, 3.8) treatment-related teaes 35.4 (32.9, 38.0) 29.4 (27.4, 31.5) 42.3 (38.8, 45.9) 21.1 (18.8, 23.5) 28.9 (26.8, 31.1) serious teaes 5.9 (5.1, 6.9) 5.6 (4.9, 6.4) 6.2 (5.1, 7.4) 5.4 (4.4, 6.5) 5.5 (4.8, 6.4) teaes leading to death 0.4 (0.2, 0.6) 0.4 (0.3, 0.7) 0.4 (0.2, 0.8) 0.4 (0.2, 0.8) 0.4 (0.2, 0.7) three most common teaes, eair/100 py (95% ci) nasopharyngitis 19.1 (17.4, 20.9) 15.3 (13.9, 16.7) 21.1 (18.9, 23.5) 10.0 (8.5, 11.6) 15.0 (13.6, 16.5) oral candidiasis 12.6 (11.3, 14.0) 10.2 (9.1, 11.3) 15.9 (14.1, 17.9) 7.1 (5.9, 8.5) 10.1 (9.1, 11.3) upper respiratory tract infection 8.9 (7.8, 10.1) 7.1 (6.2, 8.0) 8.9 (7.6, 10.4) 4.9 (3.9, 6.1) 6.5 (5.7, 7.4) teaes of interest, eair/100 py (95% ci) serious infections 1.0 (0.7, 1.4) 1.2 (0.9, 1.5) 1.4 (0.9, 2.0) 1.1 (0.7, 1.7) 1.2 (0.9, 1.6) active tuberculosis 0.0 0.0 0.0 0.0 0.0 fungal infections 20.1 (18.4, 22.0) 16.6 (15.3, 18.1) 25.0 (22.6, 27.6) 12.6 (10.9, 14.4) 16.7 (15.3, 18.3) oral candidiasis 12.6 (11.3, 14.0) 10.2 (9.1, 11.3) 15.9 (14.1, 17.9) 7.1 (5.9, 8.5) 10.1 (9.1, 11.3) inflammatory bowel disease 0.1 (0.0, 0.3) 0.1 (0.0, 0.3) 0.2 (0.0, 0.4) 0.1 (0.0, 0.4) 0.1 (0.0, 0.3) adjudicated mace 0.5 (0.3, 0.8) 0.6 (0.4, 0.8) 0.7 (0.4, 1.1) 0.5 (0.2, 0.9) 0.6 (0.4, 0.9) malignancies 0.8 (0.5, 1.2) 0.9 (0.6, 1.2) 0.6 (0.3, 1.1) 1.2 (0.7, 1.8) 0.9 (0.6, 1.2) nmsc 0.3 (0.2, 0.6) 0.3 (0.2, 0.6) 0.3 (0.1, 0.7) 0.3 (0.1, 0.7) 0.3 (0.2, 0.5) adjudicated sib 0.0 (0.0, 0.2) 0.1 (0.0, 0.2) 0.1 (0.0, 0.4) 0.1 (0.0, 0.3) 0.1 (0.0, 0.2) neutropenia events 0.8 (0.6, 1.2) 0.6 (0.4, 0.9) 0.8 (0.4, 1.3) 0.2 (0.0, 0.5) 0.4 (0.3, 0.7) hepatic events 4.3 (3.6, 5.2) 4.0 (3.4, 4.7) 3.7 (2.9, 4.7) 3.2 (2.5, 4.1) 3.2 (2.7, 3.8) ast or alt elevationsb >3x uln 2.4 (1.9, 3.0) 2.2 (1.7, 2.7) 2.8 (2.1, 3.6) 1.9 (1.3, 2.6) 2.1 (1.7, 2.6) >5x ulnc 0.8 (0.5, 1.2) 0.6 (0.4, 0.9) 0.7 (0.4, 1.2) 0.5 (0.2, 0.9) 0.6 (0.4, 0.9) serious hypersensitivity reactionsd 0.2 (0.1, 0.4) 0.1 (0.0, 0.3) 0.2 (0.0, 0.4) 0.1 (0.0, 0.3) 0.1 (0.0, 0.3) injection site reactions 2.3 (1.8, 2.9) 1.9 (1.5, 2.3) 2.7 (2.0, 3.5) 1.2 (0.8, 1.8) 1.8 (1.4, 2.3) data are shown as of the data cut-off (two years: 9 nov 2020; three years: 23 oct 2021). apatients are included in the relevant bkz dose group based on the dose most recently received prior to the date of the adverse event or assessment. patients who received both bkz 320 mg q4w and q8w are included in the population count of both treatment groups, but only once in each bkz total group; bnot all hepatic laboratory parameter elevations were reported as adverse events; c>3x and >5x elevations are evaluated independently, hence patients with >5x elevations are also included in the >3x data; dno anaphylactic reactions associated with bkz were reported. bkz was well-tolerated over three years of treatment. safety data were consistent with those observed over two years of bkz treatment; no safety signals were identified. the majority of patients were receiving bkz q8w by year 3. aphase 2 and phase 3 data are pooled from the initial and maintenance treatment periods of the be sure, be vivid, and be ready phase 3 trials, their openlabel extension be bright, and four phase 2 trials (be able 1, be able 2, ps0016, ps0018); bphase 3 data are pooled from the initial and maintenance treatment periods of the be sure, be vivid, and be ready phase 3 trials, and their open-label extension be bright. phase 2 and 3a phase 3b bkz total bkz q4w bkz q8w bkz total population n=1,789 n=1,456 n=1,289 n=1,495 exposure 4,245.3 py 1,965.6 py 1,914.5 py 3,876.4 py dosing 320 mg q4w 320 mg q8w 64 mg q4w (phase 2) 160 mg q4w (phase 2) 480 mg q4w (phase 2) 320 mg q4w 320 mg q8w 320 mg q4w 320 mg q8w trials administered 6 double-blinded trials and 2 oles 3 doubleblinded trials and 1 ole 2 doubleblinded trials and 1 ole 3 doubleblinded trials and 1 ole e a ir /1 0 0 p y 1 2 3 4 5 6 7 8 9 10 0 treatment period 1 yeara 2 yearsb 3 yearsc 6.6 (5.5, 7.9) 5.9 (5.1, 6.9) 5.6 (4.9, 6.4) treatment period e a ir /1 0 0 p y 250 200 150 100 50 0 1 yeara 2 yearsb 3 yearsc 238.0 (226.0, 250.5) 202.4 (192.6, 212.6) 186.1 (177.2, 195.3) bkz total over 1 year (n=1,789) bkz total over 2 years (n=1,789) bkz total over 3 years (n=1,789) error bars represent 95% cis. data are pooled from four phase 2 and four phase 3 trials. phase 2 data were not collected beyond 2 years. data are reported as of the relevant data cut-offs: a1 nov 2019; b9 nov 2020; c23 oct 2021. a) all teaes b) serious teaes c) oral candidiasis teaes e a ir /1 0 0 p y treatment period 1 yeara 2 yearsb 3 yearsc 5 10 15 20 25 30 35 0 16.4 (14.5, 18.5) 12.6 (11.3, 14.0) 10.2 (9.1, 11.3) 22tyk2083_fall clin nppa 22_poetyk high impact areas po_cp_v03.indd deucravacitinib, an oral, selective tyrosine kinase 2 inhibitor, versus placebo in scalp, nail, and palmoplantar psoriasis: subset analyses of the phase 3 poetyk pso-1 and pso-2 trials andrew blauvelt,1 phoebe rich,2 howard sofen,3 jo lambert,4 joseph f merola,5 mark lebwohl,6 lauren hippeli,7 renata m kisa,7 subhashis banerjee,7 alexa b kimball8 1oregon medical research center, portland, or, usa; 2oregon dermatology and research center, portland, or, usa; 3ucla school of medicine, los angeles, ca, usa; 4ghent university, ghent, belgium; 5harvard medical school, boston, ma, usa; 6icahn school of medicine at mount sinai, new york, ny, usa; 7bristol myers squibb, princeton, nj, usa; 8beth israel deaconess medical center, boston, ma, usa presented at the fall clinical dermatology conference for nps and pas®; june 3−5, 2022; scottsdale, az this is an encore of the 2022 maui derm for dermatologists poster this poster may not be reproduced without written permission from the authors.email for andrew blauvelt, md, mba: ablauvelt@oregonmedicalresearch.com synopsis • deucravacitinib — oral, selective tyrosine kinase 2 (tyk2) inhibitor that acts via an allosteric mechanism by uniquely binding to the regulatory domain instead of the catalytic domain of tyk21 • ≥100-fold greater selectivity for tyk2 vs janus kinase (jak) 1/3 and ≥2000-fold greater selectivity for tyk2 vs jak 2 in cells1,2 — inhibits tyk2-mediated cytokine signaling involved in psoriasis pathogenesis (eg, interleukin-23, type i interferons)1 • two 52-week, phase 3 psoriasis trials (poetyk pso-1 and poetyk pso-2) previously demonstrated that deucravacitinib was superior to placebo and apremilast at week 16 based on the coprimary endpoints3: — ≥75% reduction from baseline in psoriasis area and severity index (pasi 75) — a static physician’s global assessment score of 0 or 1 (spga 0/1; clear or almost clear skin) objectives • efficacy of deucravacitinib vs placebo at week 16 in patients with moderate to severe involvement at baseline in the pooled pso-1 and pso-2 population of: — scalp — fingernail — palms and soles (palmoplantar psoriasis) • efficacy in these high impact areas through week 52 in pso-1 patients: — with continuous deucravacitinib treatment from day 1 — after switching from placebo to deucravacitinib at week 16 methods study designs • the study designs for poetyk pso-1 and pso-2 are summarized in figure 1 • key eligibility criteria included the following: — age ≥18 years — diagnosis of moderate to severe plaque psoriasis — pasi ≥12, spga ≥3, body surface area involvement ≥10% • patient randomization was stratified by geographic region, body weight, and prior biologic use figure 1. study designs poetyk pso-1 (n = 666) poetyk pso-2 (n = 1020) deucravacitinib 6 mg qdplacebo (n = 166) deucravacitinib 6 mg qd<pasi 50 apremilast 30 mg bid≥pasi 50 titrate* 1 :2 :1 r an d om iz at io n weeks 16 24 520 deucravacitinib 6 mg qdplacebo (n = 255) deucravacitinib 6 mg qd (n = 511) deucravacitinib 6 mg qd<pasi 75 deucravacitinib 6 mg qd<pasi 75 deucravacitinib 6 mg qd deucravacitinib 6 mg qd placebob apremilast 30 mg bida (n = 254) ≥pasi 75 1 :2 :1 r an d om iz at io n weeks 16 24 520 1:1 deucravacitinib 6 mg qdplacebob deucravacitinib 6 mg qd (n = 332) primary endpoint primary endpoint apremilast 30 mg bida (n = 168) ≥pasi 75 aapremilast was titrated from 10 mg qd to 30 mg bid over the first 5 days of dosing. bupon relapse (≥50% loss of week 24 pasi percentage improvement from baseline), patients were to be switched to deucravacitinib 6 mg qd. bid, twice daily; pasi, psoriasis area and severity index; pasi 50, ≥50% reduction from baseline in pasi; pasi 75, ≥75% reduction from baseline in pasi; qd, once daily. efficacy endpoints • moderate to severe scalp psoriasis (scalp-specific pga [ss-pga] ≥3) at baseline — ss-pga 0/1 — ≥90% reduction from baseline in psoriasis scalp severity index (pssi 90) • moderate to severe fingernail psoriasis (pga-fingernails [pga-f] ≥3) at baseline — pga-f 0/1 • moderate to severe palmoplantar psoriasis (palmoplantar pga [pp-pga] ≥3) at baseline — pp-pga 0/1 — palmoplantar pasi (pp-pasi) improvements from baseline evaluation time points • weeks 0−16 in the pooled pso-1 and pso-2 population • weeks 0−52 in pso-1 (allowed continuous treatment with deucravacitinib for weeks 0−52) statistical analysis • none of the statistical comparisons of deucravacitinib vs placebo were mutiplicity controlled except for ss-pga 0/1 vs placebo at week 16 in pso-1 results baseline patient demographics and disease characteristics • in the pooled pso-1 and pso-2 population (n = 1264; table 1): — 64% (n = 808) had moderate to severe scalp psoriasis — 15% (n = 184) had moderate to severe fingernail psoriasis — 7% (n = 82) had moderate to severe palmoplantar psoriasis • presence of moderate to severe disease in these special areas was balanced overall in the deucravacitinib vs placebo group table 1. baseline patient demographics and disease characteristics poetyk pso-1 and pso-2 placebo deucravacitinib (n = 421) (n = 843) age, mean (sd), y 47.5 (13.7) 46.5 (13.5) weight, mean (sd), kg 90.6 (21.1) 90.6 (21.9) female, n (%) 127 (30.2) 277 (32.9) race, n (%) white 360 (85.5) 741 (87.9) asian 42 (10.0) 83 (9.8) other 19 (4.5) 19 (2.3) disease duration, mean (sd), y 18.9 (12.9) 18.6 (12.7) prior systemic treatment use, n (%) yes 248 (58.9) 474 (56.2) nonbiologic (± biologic) 183 (43.5) 326 (38.7) biologic 146 (34.7) 295 (35.0) no prior systemic therapy 173 (41.1) 369 (43.8) spga, n (%) 3 (moderate) 345 (81.9) 665 (78.9) 4 (severe) 75 (17.8) 178 (21.1) pasi, mean (sd) 20.9 (8.6) 21.1 (8.0) bsa, mean (sd), % 25.3 (16.1) 26.4 (15.8) ss-pga ≥3, n (%) 294 (69.8) 514 (61.0) pga-f ≥3, n (%) 72 (17.1) 112 (13.3) pp-pga ≥3, n (%) 25 (5.9) 57 (6.8) pssd symptom score, mean (sd) 50.6 (25.6) 52.1 (25.9) dlqi, mean (sd) 11.6 (6.7) 11.9 (6.6) bsa, body surface area; dlqi, dermatology life quality index; pasi, psoriasis area and severity index; pga-f, physician’s global assessment-fingernails; pp-pga, palmoplantar physician’s global assessment; pssd, psoriasis symptoms and signs diary; spga, static physician’s global assessment; ss-pga, scalp-specific physician’s global assessment. scalp psoriasis • in the pooled pso-1 and pso-2 population, significantly more patients receiving deucravacitinib vs placebo achieved ss-pga 0/1 at week 16 (figure 2) — efficacy was significantly greater with deucravacitinib vs placebo by week 1 figure 2. ss-pga 0/1a responses through week 16 (pooled pso-1 and pso-2; nri) 0 10 20 30 40 50 60 70 80 90 100 0 4 8 12 16 † † † † 64.0% † 17.3% ss -p g a 0 /1 r es po ns e ra te , % 1 2 weeks * deucravacitinib 6 mg qd (n = 514)placebo (n = 294) aincluded patients with a baseline ss-pga score ≥3. *p < 0.05 vs placebo. †p < 0.0001 vs placebo. missing data were imputed with nri. nri, nonresponder imputation; qd, once daily; ss-pga 0/1, scalp-specific physician’s global assessment score of 0 or 1. • in the pooled pso-1 and pso-2 population, significantly more patients receiving deucravacitinib vs placebo achieved pssi 90 at week 16 (figure 3) — efficacy was significantly greater with deucravacitinib vs placebo by week 1 figure 3. pssi 90a responses through week 16 (pooled pso-1 and pso-2; nri) 0 10 20 30 40 50 60 70 80 90 100 0 4 8 12 16 p s s i 9 0 re sp on se r at e, % weeks † † † 50.6% † 10.5% * 1 2 * deucravacitinib 6 mg qd (n = 514)placebo (n = 294) aincluded patients with a baseline ss-pga score ≥3. *p ≤ 0.05 vs placebo. †p < 0.0001 vs placebo. missing data were imputed with nri. nri, nonresponder imputation; pssi 90, ≥90% reduction from baseline in psoriasis scalp severity index; qd, once daily; ss-pga, scalp-specific physician’s global assessment. • in pso-1, ss-pga 0/1 responses at week 16 were maintained through week 52 with continuous deucravacitinib treatment (figure 4) — patients who crossed over from placebo to deucravacitinib at week 16 achieved comparable ss-pga 0/1 responses at week 52 to those who had received continuous deucravacitinib treatment from day 1 figure 4. ss-pga 0/1a responses through week 52 (pso-1; nri) 0 10 20 30 40 50 60 70 80 90 100 0 4 primary endpoint 8 12 16 20 24 28 32 36 40 44 48 52 ss -p g a 0 /1 r es po ns e ra te , % weeks 70.3%* 69.7% 65.6% 17.4% deucravacitinib (n = 209) placebo (n = 121) placebo-deucravacitinib (n = 109) aincluded patients with a baseline ss-pga score ≥3. *p < 0.0001 vs placebo. missing data were imputed with nri. nri, nonresponder imputation; ss-pga 0/1, scalp-specific physician’s global assessment score of 0 or 1. fingernail psoriasis • in the pooled pso-1 and pso-2 population, significantly more patients receiving deucravacitinib vs placebo achieved pga-f 0/1 at week 16 (figure 5) • in pso-1, pga-f 0/1 responses at week 16 were increased through week 52 with continuous deucravacitinib treatment (figure 6) — patients who crossed over from placebo to deucravacitinib at week 16 achieved comparable pga-f 0/1 responses at week 52 to those who received continuous deucravacitinib treatment figure 5. pga-f 0/1a responses through week 16 (pooled pso-1 and pso-2; nri) 0 10 20 30 40 50 60 70 80 90 100 0 4 8 12 16 20.5%* 8.3% p g a -f 0 /1 r es po ns e ra te , % weeks deucravacitinib 6 mg qd (n = 112)placebo (n = 72) aincluded patients with a baseline pga-f score ≥3. *p = 0.0272 vs placebo. missing data were imputed with nri. nri, nonresponder imputation; pga-f 0/1, physician’s global assessment-fingernails score of 0 or 1; qd, once daily. figure 6. pga-f 0/1a responses through week 52 (pso-1; nri) p g a -f 0 /1 r es po ns e ra te , % 0 10 20 30 40 50 60 70 80 90 100 0 4 primary endpoint 8 12 16 20 24 28 32 36 40 44 48 52 weeks deucravacitinib (n = 43) placebo (n = 34) placebo-deucravacitinib (n = 29) 20.9% 51.7% 46.5% 8.8% aincluded patients with a baseline pga-f score ≥3. missing data were imputed with nri. nri, nonresponder imputation; pga-f 0/1, physician’s global assessment-fingernails score of 0 or 1. palmoplantar psoriasis • in the pooled pso-1 and pso-2 population, significantly more patients receiving deucravacitinib vs placebo achieved pp-pga 0/1 at week 16 (figure 7) figure 7. pp-pga 0/1a responses through week 16 (pooled pso-1 and pso-2; nri) deucravacitinib 6 mg qd (n = 57)placebo (n = 25) 0 10 20 30 40 50 60 70 80 90 100 0 4 8 12 16 49.1%* 16.0% pp -p g a 0 /1 r es po ns e ra te , % 1 2 weeks aincluded patients with a baseline pp-pga score ≥3. *p = 0.0052 vs placebo. missing data were imputed with nri. nri, nonresponder imputation; pp-pga 0/1, palmoplantar physician’s global assessment score of 0 or 1; qd, once daily. • in the pooled pso-1 and pso-2 population, mean change from baseline in pp-pasi, adjusted for baseline covariates, was significantly greater with deucravacitinib vs placebo at week 16 (figure 8) — greater efficacy with deucravacitinib vs placebo was observed as early as week 4 figure 8. change from baseline in pp-pasia through week 16 (pooled pso-1 and pso-2; mbocf) deucravacitinib 6 mg qd (n = 57)placebo (n = 25) placebo (n = 25) deucravacitinib (n = 57) baseline pp-pasi, mean (sd) 17.5 (12.5) 15.9 (10.9) * * -20 -10 0 4 8 12 16 m ea n c fb in p pp a s i weeks * 3.3* 4.2 1 2 20 aincluded patients with a baseline pp-pga score ≥3. *p ≤ 0.0097 vs placebo. missing data were imputed with the modified baseline observation carried forward method. cfb, change from baseline; mbocf, modified baseline observation carried forward; pp-pasi, palmoplantar psoriasis area and severity index; qd, once daily. • in pso-1, pp-pga 0/1 responses at week 16 were maintained through week 52 with continuous deucravacitinib treatment (table 2) — patients who crossed over from placebo to deucravacitinib at week 16 achieved comparable pp-pga 0/1 responses at week 52 to those who received continuous deucravacitinib treatment table 2. pp-pga 0/1a responses through week 52 (pso-1; nri) pp-pga 0/1 response rate, % week deucravacitinib (n = 18) placebo-deucravacitinib (n = 7) 16 55.6 0 24 66.7 42.9 52 55.6 42.9 aincluded patients with a baseline pp-pga score ≥3. missing data were imputed with nri. nri, nonresponder imputation; pp-pga 0/1, palmoplantar physician’s global assessment score of 0 or 1. conclusions • in patients with moderate to severe scalp, fingernail, or palmoplantar psoriasis at baseline in pso-1 and pso-2, deucravacitinib was significantly more efficacious than placebo in improving disease burden in these high impact areas through week 16 • clinical responses were maintained or increased in pso-1 patients who received continuous deucravacitinib treatment from day 1 through week 52 — patients who crossed over from placebo to deucravacitinib at week 16 achieved comparable responses at week 52 to those who had received continuous deucravacitinib treatment from baseline • these findings support the use of deucravacitinib, an oral, selective tyk2 inhibitor, in patients with moderate to severe scalp, fingernail, or palmoplantar psoriasis references 1. burke jr, et al. sci transl med. 2019;11:1-16. 2. wrobleski st, et al. j med chem. 2019;62:8973-8995. 3. armstrong a, et al. presented at the annual meeting of the american academy of dermatology; april 23-25, 2021. acknowledgments • these clinical trials were sponsored by bristol myers squibb • writing and editorial assistance were provided by lisa feder, phd, of peloton advantage, llc, an open health company, parsippany, nj, usa, funded by bristol myers squibb disclosures ab: scientific adviser and/or clinical study investigator: abbvie, abcentra, aligos, almirall, amgen, arcutis, arena, aslan, athenex, boehringer ingelheim, bristol myers squibb, dermavant, ecor1, eli lilly, evommune, forte, galderma, incyte, janssen, landos, leo pharma, novartis, pfizer, rapt, regeneron, sanofi genzyme, sun pharma, ucb, and vibliome. pr: research (principal investigator on pharmaceutical trials): abbvie, arcutis, bristol myers squibb, dermavant, eli lilly, janssen, novartis, sun pharma, and ucb. hs: clinical investigator: abbvie, amgen, boehringer ingelheim, bristol myers squibb, eli lilly, janssen, leo pharma, novartis, and sun pharma. jl: unrestricted grants: abbvie, almirall, celgene, eli lilly, janssen-cilag, leo pharma, novartis, and ucb; speaker: abbvie, almirall, bristol myers squibb, janssen-cilag, pfizer, and ucb; consultant: abbvie, amgen, bristol myers squibb, celgene, eli lilly, janssen-cilag, leo pharma, novartis, and ucb. jfm: consultant and/or investigator: abbvie, amgen, biogen, bristol myers squibb, dermavant, eli lilly, janssen, leo pharma, novartis, pfizer, regeneron, sanofi, sun pharma, and ucb. ml: research funds on behalf of mount sinai: abbvie, amgen, arcutis, avotres, boehringer ingelheim, dermavant, eli lilly, incyte, janssen, ortho dermatologics, regeneron, and ucb; consultant: aditum bio, almirall, altrubio anaptysbio, arcutis, arena, aristea, arrive technologies, avotres, biomx, boehringer ingelheim, brickell biotech, bristol myers squibb, cara, castle biosciences, corevitas’ (corrona) psoriasis registry, dermavant, dr. reddy’s laboratories, evelo biosciences, evommune, forte biosciences, helsinn therapeutics, hexima, leo pharma, meiji seika pharma, mindera, pfizer, seanergy, and verrica. lh, rmk, and sb: employees and shareholders: bristol myers squibb. abk: consultant and investigator: abbvie, eli lilly, janssen, novartis, pfizer, and ucb; investigator: anapyts bio, bristol myers squibb, and incyte; consultant: bayer, concert, evoimmune, moonlake, and ventyx; fellowship funding: abbvie and janssen; previous member of board of directors and past president: international psoriasis council; board of directors: almirall and hs foundation. powerpoint presentation conjunctivitis in adolescent patients aged 12–17 with moderate-to-severe atopic dermatitis treated with tralokinumab up to week 52: results from the phase 3 ecztra 6 trial andreas wollenberg1,2, marjolein de bruin-weller3, jacob p. thyssen4, lisa a. beck5, eric l. simpson6, shinichi imafuku7, mark boguniewicz8, azra kurbasic9, lise soldbro9, natacha strange vest9, petra arlert9, amy s. paller10 1ludwig maximilian university of munich, department of dermatology and allergy, munich, germany; 2vrije universiteit brussel (vub), universitair ziekenhuis brussel (uz brussel), department of dermatology, brussels, belgium; 3department of dermatology and allergology, university medical center utrecht, utrecht, netherlands; 4department of dermatology, bispebjerg hospital, university of copenhagen, copenhagen, denmark; 5department of dermatology, medicine and pathology, university of rochester medical center, rochester, ny, usa; 6oregon health & science university, portland, or, usa; 7fukuoka university, fukuoka, japan; 8division of allergy-immunology, department of pediatrics, national jewish health, denver, co, usa; 9leo pharma, a/s, ballerup, denmark; 10feinberg school of medicine, northwestern university, chicago il, usa objective • to examine conjunctivitis frequency and severity in tralokinumab-treated adolescents with moderate-to-severe atopic dermatitis patient characteristics • baseline demographic and clinical characteristics were comparable across treatment groups (table 1) results • conjunctivitis frequency in adolescents was low and similar between the tralokinumab and placebo arms of the phase 3 ecztra 6 trial • conjunctivitis rates were numerically lower in adolescents compared with reported adult rates4, through week 16 of the trial • the majority of conjunctivitis events were mild, and most resolved during weeks 0–16; none led to permanent discontinuation of tralokinumab • the frequency and severity of conjunctivitis did not increase with longer-term tralokinumab treatment up to week 52 conclusions introduction • atopic dermatitis (ad) is a chronic inflammatory skin disease with limited safe and effective treatments suitable for long-term use in adolescents with moderate-to-severe disease1,2 • various forms of conjunctivitis are commonly present in adult patients with ad,3 and can increase with biological treatments targeting the type 2 inflammatory pathway4,5 • higher frequency of conjunctivitis was observed with dupilumab (which targets interleukin-4 and -13) vs placebo in an adolescent ad trial2 • tralokinumab is a fully human monoclonal antibody that binds with high affinity to interleukin-13, a key driver of ad pathogenesis6–8 • here, we examine the frequency and rate of conjunctivitis in adolescents treated with tralokinumab vs placebo in the phase 3 ecztra 6 trial tralokinumab 300 mg q2w placebo q2w tralokinumab 300 mg q2w tralokinumab 300 mg q4w alternating with placebo placebo q2w tralokinumab 300 mg q2w optional tcs and optional home use initial treatmentscreening maintenance treatment patients with clinical response iga 0/1 or easi-75 clinical response must be achieved without rescue safety follow-up open-label treatment 1:1:1 randomization patients who: • did not achieve iga 0/1 or easi-75 at week 16 • received rescue treatment between week 2–16 • were transferred from maintenance treatment if specific criteria were met washout of tcs and other ad medication initial loading dose 1:1 randomization 16 weeks0–6 weeks 52 weeks 66 weeks 1:1 randomization tralokinumab 150 mg q2w tralokinumab 150 mg q2w tralokinumab 150 mg q4w alternating with placebo n=294 figure 1. ecztra 6 trial design rescue treatment during initial and maintenance treatment defined as: tci, tcs or systemic ad treatment. ad, atopic dermatitis; easi, eczema area and severity index; iga, investigator’s global assessment; q2w, every 2 weeks; q4w, every 4 weeks; tcs, topical corticosteroids. †patients not achieving easi-75 over ≥4 weeks with iga ≥2 after iga=0 at week 16, or with iga ≥3 after iga=1 at week 16, or who had iga >1 at week 16; patients who receive rescue treatment after week 16 patients placebo (n=94) tralokinumab 150 mg q2w (n=98) tralokinumab 300 mg q2w (n=97) mean age, years 14.3 14.8 14.6 age group, n (%) 12–14 15–17 49 (52.1) 45 (47.9) 37 (37.8) 61 (62.2) 45 (46.4) 52 (53.6) male sex, n (%) 51 (54.3) 51 (52.0) 47 (48.5) mean duration of ad, years (sd) 12.1 (3.5) 12.7 (3.7) 12.1 (3.7) severe disease (iga=4), n (%) 43 (45.7) 44 (44.9) 48 (49.5) mean easi (sd) 31.2 (14.5) 32.1 (12.9) 31.8 (13.9) mean scorad (sd) 67.4 (14.9) 67.7 (14.4) 68.3 (13.7) mean cdlqi (sd) 13.3 (6.0) 12.9 (6.3) 13.4 (7.3) mean weekly average peak pruritus nrs (sd) 7.5 (1.7) 7.5 (1.6) 7.8 (1.5) ad, atopic dermatitis; cdlqi, children's dermatology life quality index; easi, eczema area and severity index; iga, investigator's global assessment; n, number of subjects in analysis set; nrs, numeric rating scale; q2w, every 2 weeks; scorad, scoring atopic dermatitis; sd, standard deviation. frequency & severity of conjunctivitis: weeks 0–16 • by week 16, 2 patients (2.1%; rate 10.7) in the placebo arm had conjunctivitis (aesi) vs 4 patients (4.1%; rate 13.6) in the tralokinumab 150 mg arm and 3 patients (3.1%; rate 10.2) in the 300 mg arm (table 3) • only two conjunctivitis aesis were reported as the preferred term ‘conjunctivitis’, both in the tralokinumab 150 mg arm • overall, 2/10 (20%) events were confirmed by an ophthalmologist • the majority of conjunctivitis aesis were considered mild in severity; no severe events were reported (table 3) references 1. weidinger s, et al. nat rev dis primers. 2018;4:1; 2. simpson el, et al. jama dermatol. 2020;156:44–56; 3. thyssen jp, et al. j am acad dermatol. 2017; 77: 280–86.e28; 4. wollenberg a, et al. br j dermatol. 2022;186:453–65; 5. akinlade b, et al. br j dermatol. 2019;181:459-73; 6. bieber t. allergy. 2020;75:54–62; 7. tsoi lc, et al. j invest dermatol. 2019;139:1480–89; 8. popovic b, et al. j mol biol. 2017;429:208–19 disclosures andreas wollenberg has received grants, personal fees, or nonfinancial support from abbvie, aileens, almirall, beiersdorf, bioderma, chugai, galapagos, galderma, gsk, hans karrer, leo pharma, lilly, l’oreal, maruho, medimmune, merck, novartis, pfizer, pierre fabre, regeneron, santen, and sanofi-aventis. marjolein de bruin-weller has served as a consultant, advisory board member, and/or speaker for abbvie, almirall, arena, aslan, galderma, janssen, leo pharma, pfizer, regeneron, and sanofi-genzyme, and eli lilly and company. jacob p. thyssen has attended advisory boards for eli lilly & co., almirall, arena pharmaceuticals, pfizer, abbvie, leo pharma, regeneron and sanofi-genzyme, been an investigator for leo pharma, sanofi-genzyme, eli lilly & co., abbvie and pfizer, and received speaker honorarium from leo pharma, pfizer, almirall, abbvie, eli lilly & co., regeneron and sanofi-genzyme. lisa a. beck has been a consultant for allakos, arena pharmaceuticals, dermtech, evelo biosciences, galderma, incyte, janssen, leo pharma, merck, numab therapeutics, pfizer, rapt therapeutics, regeneron, ribon therapeutics, sanofi/genzyme, sanofi-aventis, stealth biotherapeutics, trevi therapeutics, union therapeutics and xencor. dmc member: novartis. investigator for abbvie, astra-zeneca, dermtech, kiniksa, pfizer, regeneron, and ribon therapeutics. eric l. simpson is a consultant and investigator for regeneron/sanofi, dermira, menlo pharmaceuticals, lilly, abbvie, genentech, medimmune, gsk, leo pharma, celgene, and pfizer. shinichi imafuku is a researcher, consultant, or speaker for abbvie, amgen, celgene, daiichisankyo, eisai, kyowakirin, lilly, taihoyakuhinkogyo, tanabemitsubishi, tsumura, torii, maruho, novartis, leo pharma, and janssen. mark boguniewicz has been a clinical study investigator for regeneron and incyte and served as a scientific adviser or consultant for pfizer, abbvie, eli lilly, leo pharma, janssen, regeneron, and sanofi genzyme. azra kurbasic, lise soldbro, natacha strange vest, and petra arlert are employees of leo pharma a/s. amy s. paller has served as an investigator for abbvie, anaptysbio, incyte, janssen, krystalbio, leo pharma, regeneron, and ucb, received honorarium for consultancy from abbvie, abeona, almirall, anaptysbio, arena, azitra, biomx, boehringer ingelheim, castle biosciences, catawba, dermira, exicure, forté, kamari, leo pharma, lilly, lifemax, novartis, pfizer, regeneron, sanofi genzyme, seanergy, and ucb, and served on a data safety monitory board for abbvie, galderma, and novan. acknowledgements the ecztra 6 clinical trial was sponsored by leo pharma a/s (ballerup, denmark). this poster is an encore of a previous presentation at the 12th international symposium on atopic dermatitis, 17 – 19 october 2022. editorial support from alphabet health (new york, ny, usa) by juliel espinosa, phd and meredith whitaker, phd was funded by leo pharma (usa). scan to download a copy of this poster copies of this poster and its content, obtained through this qr code, are for personal use only and may not be reproduced without written permission from the authors outcomes of conjunctivitis: weeks 0–16 • most outcomes (8/9) were recovered or resolved during weeks 0–16, and none led to permanent tralokinumab discontinuation (table 4) aesi, adverse event of special interest; q2w, once every 2 weeks. incidence of conjunctivitis: weeks 16–52 • during weeks 16–52, 3 patients (6%; rate 11.9) had conjunctivitis (aesi) in the maintenance treatment phase (pooled tralokinumab arms) as did 11 patients (4.7%; rate 9.3) in the open-label treatment phase (table 5) • of these patients, five had events that were reported as the preferred term ‘conjunctivitis’ • all conjunctivitis aesis during weeks 16–52 (maintenance and open-label phases) were mild or moderate in severity, with no severe events recorded (table 5) • conjunctivitis was classified as an adverse event of special interest (aesi) prior to trial initiation • this broad term comprised the following preferred terms: conjunctivitis, conjunctivitis allergic, conjunctivitis bacterial, and conjunctivitis viral • results were based on the safety analysis set comprised of all patients randomized and exposed to investigational medicinal product, excluding 9 patients from two sites with good clinical practice noncompliance (n=289) • rates were calculated as: • number of events per patient-years of exposure x 100 statistical analyses and endpoints • conjunctivitis frequency and rate were examined in adolescent patients aged 12–17 years with moderate-to-severe ad treated with tralokinumab for up to 52 weeks in the phase 3 ecztra 6 trial (nct03526861) table 4. outcome of conjunctivitis aesi (weeks 0–16) materials and methods study design • adolescent patients were randomized 1:1:1 to subcutaneous tralokinumab 150 mg or 300 mg every 2 weeks (q2w), or placebo for an initial treatment period of 16 weeks • primary endpoints were investigator’s global assessment (iga) score 0/1 and ≥75% improvement from baseline in eczema area and severity index (easi-75) at week 16 • patients achieving primary endpoints without rescue treatment were re-randomized to tralokinumab q2w or every 4 weeks (q4w), at their same initial tralokinumab dosage for 36 weeks of maintenance treatment as shown in figure 1, while placebo responders continue in the placebo q2w • patients not achieving primary endpoints at week 16, those receiving rescue treatment from week 2 to week 16, and those meeting other specific criteria† were transferred to open-label treatment of tralokinumab 300 mg q2w plus optional mild-to-moderate strength topical corticosteroids (tcs) • key secondary endpoints include change in scoring ad (scorad) from baseline to week 16, reduction of worst daily pruritus numeric rating scale (nrs) (weekly average) of at least 4 from baseline to week 16, and change in children's dermatology life quality index (cdlqi) score from baseline to week 16 placebo (n=94) pye 27.9 tralokinumab 150 mg q2w (n=98) pye 29.3 tralokinumab 300 mg q2w (n=97) pye 29.5 aesi category preferred term n (%) events rate n (%) events rate n (%) events rate conjunctivitis conjunctivitis conjunctivitis bacterial conjunctivitis allergic conjunctivitis viral 2 (2.1) – – 2 (2.1) – 3 – – 3 – 10.7 – – 10.7 – 4 (4.1) 2 (2.0) – 2 (2.0) – 4 2 – 2 – 13.6 6.8 – 6.8 – 3 (3.1) – 1 (1.0) 2 (2.1) – 3 – 1 2 – 10.2 – 3.4 6.8 – severity mild moderate severe 2 (2.1) – – 3 – – 10.7 – – 3 (3.1) 1 (1.0) – 3 1 – 10.2 3.4 – 2 (2.1) 1 (1.0) – 2 1 – 6.8 3.4 – aesi, adverse event of special interest; pye, patient years of exposure; q2w, once every 2 weeks. placebo (n=94) tralokinumab 150 mg q2w (n=98) tralokinumab 300 mg q2w (n=97) n (%) rate n (%) rate n (%) rate conjunctivitis aesi drug related action taken with drug dose not changed drug interrupted 2 (2.1) 1 (1.1) 2 (2.1) – 10.7 7.2 10.7 – 4 (4.1) 1 (1.0) 3 (3.1) 1 (1.0) 13.6 3.4 10.2 3.4 3 (3.1) 1 (1.0) 3 (3.1) – 10.2 3.4 10.2 – outcome fatal not recovered/not resolved recovering/resolving recovered/resolved – – – 2 (2.1) – – – 10.7 – – – 4 (4.1) – – – 13.6 – – 1 (1.0) 2 (2.1) – – 3.4 6.8 table 3. frequency of conjunctivitis aesi (weeks 0–16) overall summary of aes: weeks 0-16 • tralokinumab was well-tolerated and the majority of adverse events (aes) in the tralokinumab and placebo arms were mild or moderate in severity (table 2) • no patterns were seen in types of serious aes and none led to any safety concerns (table 2) • the majority of aes had resolved within the initial 16-week period; only one ae led to treatment withdrawal and was not considered related to treatment* (table 2) table 2. ecztra 6 safety summary (weeks 0-16) *cerebrovascular accident, not considered related to treatment by the investigator or study sponsor; the patient had several risk factors for developing cerebrovascular accident. the event was not considered related to treatment with tralokinumab by either investigator or sponsor/leo. the outcome was reported as recovered with sequelae. †includes the preferred terms conjunctivitis, conjunctivitis bacterial, conjunctivitis allergic and conjunctivitis viral (no cases of conjunctivitis viral were observed) ae, adverse event; q2w, every 2 weeks. table 1. baseline characteristics maintenance treatment open-label treatment tralokinumab pooled total 150/300 mg q2/4w (n=50) pye 25.3 tralokinumab 300 mg q2w plus optional tcs (n=234) pye 151.1 aesi category preferred term n (%) events rate n (%) events rate conjunctivitis conjunctivitis conjunctivitis bacterial conjunctivitis allergic conjunctivitis viral 3 (6.0) 1 (2.0) – 2 (4.0) – 3 1 – 2 – 11.9 4.0 – 7.9 – 11 (4.7) 4 (1.7) 3 (1.3) 4 (1.7) – 14 6 4 4 – 9.3 4.0 2.7 2.7 – severity mild moderate severe 1 (2.0) 2 (4.0) – 1 2 – 3.95 7.90 – 9 (3.8) 3 (1.3) – 10 4 – 6.6 2.7 – aesi, adverse event of special interest; pye, patient years of exposure; q2w, once every 2 weeks; tcs, topical corticosteroid table 5. incidence of conjunctivitis (weeks 16–52) placebo (n=94) tralokinumab 150 mg q2w (n=98) tralokinumab 300 mg q2w (n=97) adverse events, n (%) 58 (61.7) 66 (67.3) 63 (64.9) serious adverse events, n (%) 5 (5.3) 3 (3.1) 1 (1.0) severity, n (%) mild moderate severe 40 (42.6) 31 (33.0) 7 (7.4) 48 (49.0) 33 (33.7) 5 (5.1) 47 (48.5) 32 (33.0) 3 (3.1) leading to withdrawal, n (%) 0 1 (1.0) 0 aes of special interest, n (%) eye disorders conjunctivitis† eczema herpeticum skin infections requiring systemic treatment injection site reactions 2 (2.1) 2 (2.1) 1 (1.1) 2 (2.1) 1 (1.1) 4 (4.1) 4 (4.1) 1 (1.0) 5 (5.1) 9 (9.2) 4 (4.1) 3 (3.1) 0 2 (2.1) 7 (7.2) skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 384 research letter absorbable sutures in the covid-19 era: a post-operative quality improvement survey of patient satisfaction rates following mohs surgery andrew m. armenta md1, renat ahatov bs2, kristyna gleghorn md1, frank t. winsett md1, richard f. wagner jr. md1 1 the university of texas medical branch, department of dermatology, galveston, texas 2 the university of texas medical branch, school of medicine, galveston, tx mohs surgery is performed on 876,000 tumors per year.1 the general method of closure following removal of these tumors involves suture material. absorbable sutures have been used since as early as 1860.2 they are commonly used during mohs surgery for closure of skin and subcutaneous tissue. non-absorbable sutures or staples are often used for closure of the most superficial layer of skin, however they require a follow-up visit in the clinic for removal. during the covid-19 era, using absorbable sutures for all layers of skin has become popularized. the advantage to this technique is the elimination of a follow-up suture removal visit, thereby reducing patient exposure to covid-19. due to absorbable sutures increasing popularity it would be helpful to determine their satisfaction rates among patients. an irb exempt quality improvement survey was conducted with 38 patients who received a mohs procedure and elected for simple interrupted superficial absorbable suture placement. type of suture, type of repair, size of repair, location, age, and gender were recorded for each patient. a post-operative phone call was made to these patients at weeks 2, 4, and 8 to gauge satisfaction rates across several parameters using likert scale questions (figure 1). these surveys were analyzed to determine patient satisfaction rates and their experience with absorbable sutures. the patients were asked to rate their cosmetic outcome, perception of decreased exposure to covid-19 by eliminating suture removal appointment, comfort level on decreased post-operative visits/wound checks due to eliminating suture removal appointment, and their likelihood to opt for absorbable sutures in the future or recommend them to a friend/family (figure 2). skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 385 figure 1. likert scale survey questions at post-operative weeks 2, 4, and 8. figure 2. mean patient scores for likert scale questions (score of 1-5) across post-operative weeks 2, 4, and 8. skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 386 absorbable sutures led to high patient satisfaction in terms of cosmetic outcome, comfort level without a suture removal appointment or wound check, and the likelihood to recommend them to a family/friend and opt for absorbable sutures again in the future. however, respondents did not feel the elimination of a follow-up suture removal visit reduced their exposure to covid-19. additionally, patients who had a repair with 5-0 plain gut suture answered consistently higher on q1 (cosmetic outcome), q4 (likelihood to recommend absorbable sutures to family/friend), and q5 (likelihood of opting for absorbable sutures again in the future) than those who had repair with 3-0 or 4-0 chromic suture, and this difference was statistically significant (p<0.05). other parameters including type of repair, size of repair, location, age, and gender did not reveal any statistically significant correlation with likert scale scores. although patients did not feel the elimination of a suture removal appointment protected them from covid-19, the data overall demonstrated favorable patient perceived outcomes regarding absorbable suture placement. this can be utilized in clinical practice and may be expanded upon in future studies. absorbable surface sutures may be favored by patients who travel far distances for care or would prefer not to return for a follow-up appointment. conflict of interest disclosures: none funding: none corresponding author: andrew m. armenta, md 301 university blvd 4.122, mccullough galveston, tx 77550-0783 phone: (214) 608-2830 email: amarment@utmb.edu references: 1. asgari m, olson j, alam m. needs assessment for mohs micrographic surgery. dermatol clin. 2012;30(1):167-75. doi:10.1016/j.det.2011.08.010 2. gibson t. evolution of catgut ligatures: the endeavours and success of joseph lister and william macewen. br j surg. 1990 jul;77(7):824-5. doi: 10.1002/bjs.1800770736. pmid: 2200561. objective to demonstrate the ability of the mindera health dbp to extract actionable quantities of mrna from lesional skin of psoriasis patients, and explore the body-site dependence of this method. methods using the dbp, a total of 416 transcriptomes were collected from 24 di!erent body areas; each transcriptome was comprised of ~7,000 biomarkers. samples were collected from research sites (n=15) under an irb-approved protocol. after collection, samples were placed in a storage bu!er between 2–8˚c for transport and processing. once received, next generation sequencing (ngs) was performed according to standard procedures. measurements were made of the gene detection rate and mrna yield. additionally, a subset of samples was analyzed at various time points after sample collection (1-10 days) to determine mrna stability during storage and transport. figure 1. dermal biomarker patch workflow. figure 2. (a) graphical depiction of dbp micro-projections. these projections are chemically modified to specifically bind to mrna in the skin. (b) en face histology of dbp application. to assess the depth of penetration by the dbp, ex vivo skin samples were sliced en face and resulting puncture sites were quantified. on average, >90% of the dbp projections penetrated 350-400 µm into the skin. results figure 3. gene detection rates from various body sites (n = 416). the gene detection rate ranged from 1.1% to 76.2%. the average gene detection rate was 43.3%. based on a "20% gene detection rate acceptance criterion, >96% of the samples passed quality control metrics. statistical analysis of the data set demonstrated no statistically significant di!erence observed between body sites (anova, p=0.342), in contrast to previously published data using stratum corneum tape stripping.* figure 4. yield of mrna extracted from dbps (n=412). the acceptance level for minimum concentration was determined to be 2-5 ng of amplified rna at a concentration of 0.2 ng/µl. the yields of amplified mrna ranged from 12–2,240 ng with an average yield of 360 ng, >100-times larger than the published average yields from stratum corneum tape stripping.* all samples passed the acceptance criterion of >4 ng and yielded acceptable results in downstream sequencing. figure 5. influence of time between collection and processing on quality of dbp rna-seq data. a subset of 373 psoriasis skin samples was collected from research sites, stored in storage bu!er at 2–8˚c, and transported in an insulated shipper system at 2–8˚c overnight for downstream analysis. to substantiate mrna stability, the gene detection rates were determined for samples stored from 1 day to 10+ days. a total of 94.7% of the samples exceeded the qc threshold of 20% gene detection. synopsis the dermal biomarker patch (dbp) platform e#ciently captures transcriptomes of >7,000 biomarkers from the lesional skin of psoriasis patients in su#cient quantities for next-generation sequencing protocols. there was no significant body-site variation observed, in contrast to stratum corneum tape stripping.* this platform makes precision medicine in dermatology a reality. it provides a powerful tool for doctors, researchers, and patients to better understand the skin. funding for this project was provided by mindera health. * wong r, tran v, talwalker s, benson nr. analysis of rna recovery and gene expression in the epidermis using non-invasive tape stripping. j dermatol sci. 2006, 44(2):81-92. a dermal biomarker patch displays excellent analytical performance and outperforms tape stripping in psoriatic skin a b tobin j. dickerson, phd, stephen boyd, bs, eric andrade, bs, christian abaya, bs, yipeng wang, md, phd, and byung-in lee, phd mindera health, 5795 kearny villa road, san diego, ca 92123 amplified mrna yield from dbp conclusion the mindera health dermal biomarker patch platform has been proven to reliably extract the skin transcriptome in a minimally invasive manner. success in psoriasis patients includes: • highly reproducible e#ciency of extraction • excellent mrna yields suitable for rna-seq protocols • >96% of samples passing quality control metrics • no body-site bias in transcriptome extraction skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 625 brief article a case of dasatinib-induced keratosis pilaris olivia arriaza, bs1, frank winsett, md2, janice wilson, md2, brent kelly, md2 1john sealy school of medicine, the university of texas medical branch, galveston, tx 2department of dermatology, the university of texas medical branch, galveston, tx dasatinib is a second-generation tyrosine kinase inhibitor (tki) that is indicated for treatment of chronic myeloid leukemia (cml). mechanistically, it targets several proteins specific to cancer pathogenesis as they are involved in differentiation, proliferation, and survival. the main proteins targeted are bcr-abl, src, c-kit and pdgfr.1 dasatinib is structurally similar to the first-generation kinase, imatinib, but has a 325-fold greater potency and is effective against most imatinib-resistant kinase domain mutations.1 although, dasatinib has a high safety profile and is generally well tolerated, drucker et al found a 23.3% incidence of all-grade rashes and 1.1% incidence of high-grade rashes associated with dasatinib.2,3 clinical presentation of rashes from this study were described as pruritic, keratosis pilaris-like eruptions.2 cutaneous reactions are a welldocumented side effect of first and secondgeneration tkis, however, there are limited reports of dasatinib induced rash.4,5 further, the mechanism of rashes due to tkis are theorized to be pharmacologic rather than immunologic as symptoms are generally dose-dependent and resolve upon cessation of dosing.6 unfortunately, it is not always possible to discontinue tki treatment and therefore cutaneous side effects may be treated pharmacologically. as of now, evidence-based guidelines have not been established for management of dasatinib induced cutaneous side effects, but eruptions that are suggestive of inflammatory processes can be managed with topical corticosteroids.2,7 we report a case of persistent keratosis pilaris occurring in a young male that was abstract dasatinib is a second-generation tyrosine kinase inhibitor (tki) indicated for treatment of chronic myeloid leukemia (cml). dasatinib targets several proteins specific to cancer pathogenesis such as bcr-abl, src, c-kit and pdgfrb. cutaneous reactions are a welldocumented side effect of many tkis, however, there are limited reports and characterization of dasatinib induced rash. we report a case of keratosis pilaris and follicular epithelial thinning in a 19-year-old patient one month after beginning dasatinib for treatment of cml. this report suggests a possible role of dasatinib in the induction of epithelial follicular instability via reduced src activity and subsequent down regulation of egfr. introduction case report skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 626 exacerbated upon beginning treatment of cml with dasatinib. a 19-year-old-male was diagnosed in august 2017 with cml that was confirmed through bone marrow biopsy resulting in bcr/abl fusion in 91% of the nuclei. at that time, he was started on chemotherapy consisting of imatinib 400 mg daily. the patient was switched from imatinib to dasatinib because of lack of documented cytogenic/molecular remission after 2.8 years on imatinib. throughout the duration of imatinib treatment, the patient experienced an intermittent mild, pruritic papular rash over his upper extremities that spread to his abdomen and chest. once the patient switched to dasatinib, the severity of the rash worsened significantly. the patient described it as extremely pruritic and exacerbated by heat. the patient briefly took himself off the medication for an entire month (february 2021) without resolution of the rash and has since restarted dasatinib. the patient presented to dermatology in may 2021, with abundant uniform spiky follicular papules covering the trunk, arms, thighs, back and face (figure 1). clinically, our patient’s rash was consistent with keratosis pilaris. a punch biopsy was taken. histopathological analysis revealed follicular epithelial thinning affecting mainly the upper portion of the hair follicle, leading to free hair shafts with a mild associated reactive inflammatory infiltrate. the overlying follicular ostia contained parakeratotic debris with mild associated perifollicular acanthosis (figure 2). the patient was started on triamcinolone 0.1% cream twice daily, applied to affected areas and over the counter ammonium lactate lotion applied all over, every day. it is well known that one of the most common non-hematologic adverse effects of tkis cutaneous reactions, however, there is little evidence of cutaneous side effects associated with dasatinib.8 although, keratosis pilaris-like eruptions are the most common adverse cutaneous effects reported from dasatinib treatment, they have not been well characterized as morphologies are varied.2,5,9 bergman, et al. describes a case of neutrophilic dermatosis associated with dasatinib that presented as recurrent erythematous plaques on the face, neck, chest, arms and back. biopsies showed a variably cellular, superficial, and deep perivascular and interstitial predominantly neutrophilic infiltrate without evidence of vasculitis.9 in our case, biopsy remarkably revealed destabilization of follicular epithelium characterized by follicular epithelial thinning leading to follicular rupture on histopathology. the typical epidermal hyperkeratosis, hypergranulosis and plugging of individual hair follicles of regular keratosis pilaris was not observed, despite our patient’s clinical presentation being consistent with keratosis pilaris. differential diagnosis of keratosis pilaris includes other follicular disorders such as follicular hyperkeratotic spicules, trichodysplasia spinulosa, disseminate and recurrent infundibular folliculitis, disseminated spiked hyperkeratosis and multiple digitate hyperkeratosis. characteristics of these diseases in respect to clinical manifestations, histopathological findings and their associated conditions are summarized in table 1. follicular destabilization is thought to underlie the common acneiform rash that can be seen with tki therapy, especially those discussion skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 627 figure 1. uniform spiky follicular papules covering the chest, abdomen, arms, and back skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 628 figure 2. follicular epithelial thinning affecting mainly the upper portion of the hair follicle, leading to free hair shafts with a mild associated reactive inflammatory infiltrate. the overlying follicular ostia contained parakeratotic debris with mild associated perifollicular acanthosis skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 629 table 1. clinical findings, histopathology, and associations of the differential diagnosis for keratosis pilaris diseases clinical findings histopathology associations follicular hyperkeratotic spicules tiny hyperkeratotic spicules in follicular distribution and predominantly on the face infundibular hyperkeratosis, focal parakeratosis, and mild acanthosis with evidence of follicular plugging multiple myeloma trichodysplasia spinulosa numerous keratotic spicules on follicular erythematous papules, disproportionately affects the face follicular hyperkeratosis and multiple vellus hairs enveloped by a keratotic sheath within a dilated hair follicle viral associations in immunocompromised hosts disseminate and recurrent infundibular folliculitis hundreds of uniform, skin-colored papules likened to “goose bumps”. presents on the trunk, neck, and upper extremities mild inflammation of the follicular infundibulum primarily seen in adults with darkly pigmented skin disseminated spiked hyperkeratosis widely disseminated small spikes of keratin that are unrelated to hair follicles digitate orthokeratosis with moderate epidermal cell hyperplasia and a normal underlying dermis familial, early adulthood multiple digitate hyperkeratosis fine filiform hyperkeratotic lesions. predominately affects the trunk and extremities nonfollicular, focal columns of orthokeratosic hyperkeratosis emerging from a raised epidermis with significant stratum granulosum familial, sporadic, post-inflammation, paraneoplastic skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 630 that modulate the epidermal growth factor receptor (egfr) pathway, as egfr signaling is important in hair follicle homeostasis.7,10,11 although dasatinib does not result in direct inhibition of egfr, targeted activity against src down-regulates egfr activity.10,12 this suggests a possible role of dasatinib in the induction of follicular instability via reduced egfr activity, leading to a phenomenon similar to that seen in patients on egfr inhibitors. we report a case of keratosis pilaris induced by dasatinib treatment that histologically revealed evidence of follicular destabilization, characterized by follicular epithelial thinning, leading to follicular rupture. this specific characterization has not yet been reported and proposes further questioning of the relationship between reduced src and egfr down regulation. conflict of interest disclosures: none funding: none corresponding author: olivia arriaza, bs john sealy school of medicine the university of texas medical branch 1605 market st, galveston, tx 77550 phone: (817) 470-1651 email: ocarriaz@utmb.edu references: 1. hořínková j, šíma m, slanař o. pharmacokinetics of dasatinib. prague med rep. 2019;120(2-3):52-63. doi:10.14712/23362936.2019.10 2. drucker am, wu s, busam kj, berman e, amitay-laish i, lacouture me. rash with the multitargeted kinase inhibitors nilotinib and dasatinib: meta-analysis and clinical characterization. eur j haematol. 2013;90(2):142-150. doi:10.1111/ejh.12052 3. gambacorti-passerini c, aroldi a, cordani n, piazza r. chronic myeloid leukemia: second-line drugs of choice. am j hematol. 2016;91(1):67-75. doi:10.1002/ajh.24247 4. cortes je, jones d, o’brien s, et al. results of dasatinib therapy in patients with early chronic-phase chronic myeloid leukemia. j clin oncol. 2010;28(3):389-404. doi:10.1200/jco.2009.25.4920 5. patel ab, solomon ar, mauro mj, ehst bd. unique cutaneous reaction to secondand third-generation tyrosine kinase inhibitors for chronic myeloid leukemia. dermatology. 2016;232(1):122-125. doi:10.1159/000437383 6. amitay-laish i, stemmer sm, lacouture me. adverse cutaneous reactions secondary to tyrosine kinase inhibitors including imatinib mesylate, nilotinib, and dasatinib. dermatol ther. 2011;24(4):386-395. doi:10.1111/j.1529-8019.2011.01431.x 7. huang x, patel s, ahmed n, seiter k, liu d. severe toxicity of skin rash, fever and diarrhea associated with imatinib: case report and review of skin toxicities associated with tyrosine kinase inhibitors. drug des devel ther. 2008;(2):215-219. doi:10.2147/dddt.s3843 8. tarantini f, anelli l, ingravallo g, et al. skin lesions in chronic myeloid leukemia patients during dasatinib treatment. cancer manag res. 2019;11:7991-7996. doi:10.2147/cmar.s217872 9. bergman jc, ly ty, keating mm, hull pr. recurrent and fixed neutrophilic dermatosis associated with dasatinib. j cutan med surg. 2018;22(6):621-623. doi:10.1177/1203475418775663 10. lin yc, wu mh, wei tt, et al. degradation of epidermal growth factor receptor mediates dasatinib-induced apoptosis in head and neck squamous cell carcinoma cells. neoplasia (united states). 2012;14(6):463475. doi:10.1596/neo.12300 11. ensslin cj, rosen ac, wu s, lacouture me. pruritus in patients treated with targeted cancer therapies: systematic review and meta-analysis. j am acad dermatol. 2013;69(5):708-720. doi:10.1016/j.jaad.2013.06.038 12. chen z, oh d, dubey ak, et al. egfr family and src family kinase interactions: mechanics matters? curr opin cell biol. 2018;51:97-102. doi:10.1016/j.ceb.2017.12.003 conclusion skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 90 in-depth review granulomatous mastitis with erythema nodosum: case report and systematic review nwanneoma ngonadi, msc1, brian florenzo, bs, ba1, seth martin, md2, r. hal flowers, md2 1 university of virginia school of medicine, charlottesville, va 2 department of dermatology, university of virginia, charlottesville, va first described in 1972 by kessler and wolloch, granulomatous mastitis (gm) is a rare idiopathic chronic inflammatory disease in women of childbearing age, often mimicking breast carcinoma or breast abscess 1, 2. it often presents in women with a recent history of pregnancy or lactation 2 as a unilateral mass in any quadrant of the breast except the subareolar area, frequently with skin or lymph node involvement 1. the etiology of gm remains unknown, and it is often a diagnosis of exclusion with non-specific features on histopathologic evaluation 1. therapeutic management depends on severity of disease, and a tailored approach may include close observation and follow up, immunosuppressive medications, and/or surgical management. while prior reviews of gm have been performed, the association of gm with erythema nodosum (en) has not been well-characterized. we present a classic case of en in a patient with gm. a comprehensive review of the literature revealed numerous other similar cases, which we have compiled here in order to describe common features of this association. a 34-year-old hispanic female patient, gravida 5 para 3, with history of diabetes mellitus and hypothyroidism initially presented with progressively worsening right sided breast pain in the setting of an enlarging ipsilateral breast mass. she denied any recent history of breastfeeding or nipple discharge and was over two years postpartum. she was given amoxicillinclavulanate twice daily for ten days for presumed mastitis without improvement. mammogram showed an irregular and indistinct high-density mass in the upper outer quadrant of the right breast with associated abnormal lymph nodes; abstract although once considered a rare association, gm associated with en is increasingly recognized, and since 1987, a total of 28 reports have detailed 59 cases (including the present case). here, we provide a comprehensive review of all 58 reported cases of this association, including ours. we found a preponderance of cases occurred in females of turkish ancestry around the fourth decade of life in the peripartum period. arthralgia is the most common additional symptom. the majority of cases responded to treatment with oral corticosteroids, but some required the addition of other immunosuppressants and/or definitive surgical excision. introduction case skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 91 subsequent core needle biopsy of the breast mass diagnosed granulomatous mastitis. approximately three weeks from the onset of her breast symptoms, she developed progressively enlarging painful nodules on her knees, lower extremities, and forearms. physical examination in the dermatology clinic revealed a 5x8 cm tender indurated plaque on right lateral breast with no erythema, discharge or fluctuance (figure 1a). exam also showed multiple tender, erythematous subcutaneous nodules scattered over the extensor surfaces of bilateral upper and lower extremities (figure 1b). punch biopsy of a characteristic nodule on the right forearm exhibited a mixed septal and lobular panniculitis with acute neutrophilic inflammation with granulomatous changes, consistent with erythema nodosum. chest x-ray, hiv testing and quantiferon gold testing were performed and were normal/negative. the patient was initiated on a prednisone taper starting at 0.5 mg/kg/day. she experienced initial improvement figure 1. a) granulomatous mastitis b) erythema nodosum on prednisone but was transitioned to methotrexate after a flare. the size and induration of the breast mass steadily decreased on this therapy with eventual resolution of the erythema nodosum over the next three months. protocol and research strategy this systemic literature review was completed in accordance with the preferred reporting items for systemic reviews and meta-analysis (prism) criteria. using these guidelines, we entered (granulomatous mastitis) and (erythema nodosum) in two databases (pubmed and ovid medline) up to april 2021, from which 51 records were identified. study selection and measures the 51 records were screened and examined. those without a full copy of the manuscript in english, non-human studies, and studies with a well-established etiology other than granulomatous mastitis were excluded. the remaining records were imported into zotero, and duplicates were removed. in the end, the 27 studies with a total of 58 patient reports that met our criteria were analyzed in addition to our case. case data retrieved included demographic information, gestational status/history, disease duration, treatment efficacy, accompanying symptoms, as well as pathology and laboratory results demographic characteristics of patients with concurrent gm/ en current literature provided cases of gm/en where parturition status, age, and ethnic methods results a . b skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 92 data are included, the results of which are summarized in table 1. overall, the average age of onset for gm/en was 3 2.9 ± 4.91 years (with a range 23-43 years old). of these cases, 29 (49.2%) patients were postpartum when their symptoms first developed. some patients presented as early as 2-3 months post-partum while others developed gm/en years later, though this data was limited by inconsistent reporting. among the reports that included specific timeframes, eight (13.6%) patients were pregnant when their symptoms first developed, six (10.2%) were nulliparous, and sixteen (27.1%) patients had an unknown gestational status. with respect to demographics, gm/ en has been reported in every racial group. however, a predominance of cases was reported in women of turkish ancestry (64.4%), with hispanic patients (10.1%) at a distant second 3-15. additional affected groups can be found in table 1, and include european, east asian, and persian individuals amongst others. histopathology and laboratory findings thirty-two described gm/en cases in the literature include relevant breast biopsy data, details of which can be seen in table 2. of these, 32 (100%) showed granulomatous infiltrate, 15 (46.9%) contained lymphocytic infiltrate, 14 (43.8%) noted the presence of neutrophils, 9 (28.1%) had ductal/lobular inflammation or fibrosis, 6 (18.8%) contained abscesses, 2 (6.3%) stained for gram positive bacilli, and 1 (3.1%) contained acid-fast bacilli. descriptive histological reports of en lesions associated with igm were rarely reported, and the two available showed a granulomatous infiltrate with histiocytes, lymphocytes, multinucleate giant cells, and rare eosinophils (10, 15). patients with gm/en showed several notable serologic abnormalities, which are exhibited in table 3. significant abnormalities included 11 cases with leukocytosis (range of 11.1-19.3k /µl), 14 cases with elevated erythrocyte sedimentation rate (range 34-114 mm/ hr.), and 12 cases with increased c-reactive protein (range 15-374,000 mg/l). pertinent negative findings in some cases included normal liver function, creatinine, bun, calcium, angiotensin-converting enzyme, prolactin levels, and no evidence of autoantibodies 3, 4, 6, 16, 17. disease course and treatment efficacy overall, the average duration of gm was 14 ± 9.9 weeks, with many patients experiencing symptoms for more than 20 weeks 8, 11, 18. the mean time for en to appear was 1.60 ± 2.43 weeks after the initial presentation of the gm, with a range of 0-8 weeks. the most common additional symptom reported was arthralgias, which was present in 22 cases. the arthralgias experienced by these patients tended to be polyarticular and common joints affected included knees, wrists, and shoulders. additional symptoms or findings included fever in 12 cases, dyspnea or cough in 2 patients, and the presence of general malaise and multinodular goiter in 1 case each. of the 59 gm/en patients, 15 (25.4%) had failed antibiotic regimens before being worked up for inflammatory syndromes, and 29 patients (49.2%) were successfully treated with an initial course oral corticosteroid. generally, cases of recurrent or unresponsive gm/en were successfully treated with more aggressive measures such as surgery, higher steroid doses, or additional drug combinations. there were two reported cases of patients being skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 93 switched to higher doses of oral corticosteroids after failing other treatment regimens, with one patient requiring up to 60 mg/day of prednisone 19. table 1. demographic factors in patients with co-occurring en and gm trait cases of gm and en age; average (n) 32.9 +/4.91 (57) gestational status; n (%) post-partum 29 (49.2) pregnant 8 (13.6) nulliparous 6 (10.2) unknown 16 (27.1) ethnicity; n (%) turkish 38 (64.4) hispanic 6 (10.1) european 5 (8.5) east asian 4 (6.8) persian 3 (5.1) south asian 1 (1.7) african american 1 (1.7) unknown 1 (1.7) table 2. histological profile of gm and en lesions in literature pathology finding frequency of described pathology findings, n (%) granulomatous infiltrate 32 (100%) lymphocytes 15 (46.9%) neutrophils 14 (43.8%) ductal/ lobular inflammation or fibrosis 9 (28.1%) abscesses 6 (18.8%) other bacteria 2 (6.3%) acid fast bacilli 1 (3.1%) skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 94 table 3. compiled additional findings in gm with en cases as reported in literature finding number of reported cases additional symptom (n) arthritis 22 fever 12 dyspnea/ cough 2 malaise 1 goiter 1 abnormally elevated lab values (range) esr 14 (34-114 mm/hr) crp 12 (15-374,000 mg/l) wbc 11 (11.1-19.3 k/ul) though 31 cases (52.5% of all gm/en patients) responded to oral corticosteroids, 5 cases did not adequately respond and required excisional surgery of the gm or mastectomy 6, 11. in addition, five cases of gm/en recurred after successful treatment with steroids, of which 2 eventually underwent excisional surgery6, 1 was switched to a higher steroid dose 19, and 2 were switched to a higher steroid dose plus methotrexate 21, 26. three cases treated with corticosteroids failed to completely resolve the gm and patients were left with a residual mass 20, 1. overall, corticosteroids resolved symptoms in 69.0% of patients that took them as a first line therapy. recurrences occurred in 11.9% of patients, 7.1% were left with a residual mass, and 11.9% did not respond to corticosteroid therapy. the mean time for en to resolve after the initiation of oral glucocorticoids was 3.3 ± 4.7 weeks 4, 6, 18. the response of gm to treatment was more delayed, as most patients experienced a gradual reduction in the size of breast masses until resolution or treatment failure 1, 4, 9, 20. eleven patients (18.6%) in our study were successfully treated with surgical excision, mastectomy, or drainage, and there were no cases in which surgical treatment failed to resolve symptoms. additional treatments mentioned in the literature are summarized in table 4. patients generally responded well to combination therapy with corticosteroids plus excisional surgery or another immunosuppressant. at least one patient was treated successfully with nsaids alone 16, while two others resolved with anti-tb therapy 8 and doxycycline, respectively 15. to our knowledge, this is the largest systematic review examining the growing association, successful treatments, and disease course of granulomatous mastitis with erythema nodosum. our review again demonstrated a predominance of cases in discussion skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 95 table 4a. overview of recorded treatments for gm with en treatment (n) patients with complete resolution (n) recurrence after initial resolution (n) residual mass remaining after treatment (n) no resolution (n) corticosteroids (43) 31 5 3 5 surgical excision, drainage, or mastectomy (11) 11 corticosteroids + surgical excision (3) 2 1 corticosteroids + methotrexate (4) 3 1 corticosteroids + azathioprine (1) 1 corticosteroids + azathioprine + colchicine (1) 1 colchicine (1) 1 anti-tuberculosis regimen (1) 1 nsaids (1) 1 antibiotics 1 potassium iodide (1) 1 potassium iodide + nsaid (1) 1 refused treatment (1) 1 table 4b. treatment substitution for recurrent or unresponsive gm with en ineffective treatment substitute treatment resolution potassium iodide 900 mg/ day surgical excision and drainage y prednisolone 5mg taper prednisolone 60 mg taper y prednisolone taper 40mg--> 15mg/ day prednisolone taper 50 mg/day + methotrexate 4mg/ wk y surgical drainage + prednisolone 5mg/day prednisolone taper 40 mg--> 10 mg/day y methylprednisolone taper 0.8 mg/kg/day excisional surgery y potassium iodide 18 drops/day and indomethacin 150mg/day colchicine 1.5 mg/day y corticosteroid treatment (unspecified) mastectomy y corticosteroid treatment (unspecified) mastectomy y corticosteroid treatment (unspecified) mastectomy y corticosteroid treatment (unspecified) mastectomy y corticosteroid treatment (unspecified) excision y corticosteroid treatment (unspecified) excision y prednisolone taper 40mg prednisolone taper + mtx (15mg/week) y parous females in their late 20s and early 30s. two previous reviews of 29 and 17 gm/en cases found the average age of onset to be 32.9 and 31.4 respectively, similar to average age of 32.9 in this review 12, 21. many previous reports have noted a possible association between parturition status and igm. to our knowledge, no prior gm/en reviews have examined post-partum status and very few reports specified the exact timing of prior births, which is why precisely correlating the two has remained elusive. analysis of two prior cohorts consisting of 11 and 6 gm/en patients respectively revealed that 63.6% and 66.7% of patients had a history of parturition, which are higher than our finding of 49.2% 4, 3. given that this is the first systemic review to examine this metric, this difference may be the result of a skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 96 higher volume of patients or the fact that a significant portion of reports (27.1%) failed to include parturition history. one prior review specifically examined the occurrence of gm/en in actively pregnant patients. they found a similar concurrence (17.6%) to our finding of 13.6% 12. in addition to pregnancy, multiple sources reported an increased incidence of gm in women with oral contraceptive use, alpha-1 antitrypsin deficiency, and/or hyperprolactinemia 1, 3, 22, 7. the relationship between these factors and the development of the disorder remains an area of potential further study. while the exact etiology of gm remains unknown, several literature sources have suggested that autoimmune processes are critical to disease pathogenesis and progression. recent work by koksal et al. in 2019 and 202023, 24 revealed correlations between specific hla types and increased levels of the proinflammatory cytokines il-8 and il-17. a similar study by saydam et al. found abnormal levels of il-22 and il-23, but normal levels of il-17 in patients with gm25. correlating the frequency of specific hla types and cytokine profiles with populations at higher risk for developing gm and/or en is an area that requires further investigation and could potentially explain the increased incidence of gm/en in individuals of turkish and hispanic descent. regarding triggering events, some have proposed that it could be an immune response to ductal epithelial damage resulting in luminal secretions infiltrating the lobular connective tissue 26. this could lead to a local inflammatory reaction that would prompt macrophage and lymphocyte migration to the region 3, 6. if true, this would also explain increased incidence of gm in patients who are hyperprolactinemic, currently pregnant, or recently pregnant since these conditions are known to increase luminal secretions. while only 28.1% of histology reports included in this review specifically mentioned ductal or lobular infiltrate, it is worth noting that its exclusion from descriptions does not necessarily indicate its absence, and its role in gm/en should continue to be studied. while the common temporal relationship between gm and pregnancy, lactation, and post-partum status may suggest hormonal dysfunction as a driver, one must also take into account the normal fluctuation in cytokine profiles that occurs during and following pregnancy 3, 27. it is the opinion of the authors that the growing body of literature suggests a primary role of immune dysfunction in the pathogenesis of gm/en. the pathophysiologic relationship between gm and en continues to be debated, but the frequency of co-occurrence has been welldescribed. all available gm histology reports in our study noted the presence of granulomatous infiltrate and nearly half (46.9%) mentioned the presence of lymphocytes. very similar histology was demonstrated in the few cases of en that were biopsied. the histologic similarity is an association that previous reviews have pointed out 12. given these similarities, the two could be the result of the same underlying aberrant immune response triggered by changing cytokine levels that result in the deposition of immune complexes in the venules of the subcutaneous fat septae 3. as noted above, en generally appeared 1-2 weeks after the initial igm presentation. this correlates with the observation that autoimmune diseases and extramammary inflammatory responses, primarily nonspecific arthralgias and fever, are typically found in patients with a more severe gm presentation 1, 3, 6. the frequent skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 97 observation of arthritis in patients with gm/en even prompted parperis et al. 12 to recently propose the eponym “gmena” to describe this disease constellation of symptoms. such associations potentially indicate that these symptoms arise from a more pronounced manifestation of the same immunologic dysfunction that leads to igm alone. there remains no consensus on the treatment of gm associated with en. because gm commonly mimics numerous infectious etiologies, patients (25.4%) were often initially started on antibiotic treatments, including anti-tuberculosis regimens, vancomycin, and various beta-lactams, nearly all of which were ineffective 16, 11, 13, 18, 19. based on this review, oral prednisone at a minimum of 40mg/ day appears to be a reliable and efficacious first line therapy and can be useful in sparing patients more invasive treatments. 29 (69%) gm/en patients who were given oral steroids experienced complete amelioration of their symptoms without recurrences or the need for additional intervention. for those who were resistant to such treatment, increasing the corticosteroid dose, adding a diseasemodifying antirheumatic drug, and surgical excision were all shown to be effective strategies in resolving symptoms. none of the patients treated with these strategies were unresponsive, and it is worth noting that not a single patient treated with surgical excision or mastectomy experienced any recurrences or residual masses. given the invasive, potentially disfiguring nature of this option, we would recommend reserving this as a secondary approach in accordance with patient preferences. an additional option would be to add a second immunosuppressive medication to an existing corticosteroid regimen, but the risk/ benefit ratio of such treatments in relation to excisional surgery for treating this condition remains unclear. there is a growing body of evidence that gm is associated with extra-mamillary symptoms such as en, polyarthralgia, and fever in a minority of cases. the mechanism of the disease remains largely unknown, although aberrant cytokine levels, increased luminal secretions, hormonal dysregulation, and other drivers of immune dysfunction are implicated in its pathogenesis. the compilation of literature sources, including our present case, is highly suggestive that en can occur as a reactive process secondary to or in conjunction with gm. thus, female patients of childbearing age who present with en should also be evaluated for gm and vice versa. because extramammary symptoms are correlated with more severe cases of gm, it is crucial for physicians, especially dermatologists, to be aware of the association between en and igm in order to avoid delays in treatment and spare the patient from more invasive interventions. conflict of interest disclosures: none funding: none corresponding author: r. hal flowers iv, md department of dermatology university of virginia 1215 lee street, charlottesville, va 22908 email: rf9rj@hscmail.mcc.virginia.edu references: 1. noma, m., masahiro, o., matsuura, k., & itamoto, t. granulomatous mastitis with erythema nodosum that responded to low-dose steroid: case report and literature review of nine patients. case reports in conclusion mailto:rf9rj@hscmail.mcc.virginia.edu skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 98 clinical medicine. 2014;3: 402-406. doi: 10.4236/crcm.2014.37089. 2. halim na, uthman i, rammal r, assi hi. idiopathic granulomatous mastitis presenting as a breast pseudotumor: case reports with review of the literature. soy m, ed. case rep rheumatol. 2018;2018:4264012. doi:10.1155/2018/4264012 3. şener bahçe z, aktaş h. patients with idiopathic granulomatous mastitis accompanied by erythema nodosum. int j clin pract. published online december 10, 2020:e13928. doi:10.1111/ijcp.13928 4. akın m, karabacak h, esendağlı g, et al. coexistence of idiopathic granulomatous mastitis and erythema nodosum: successful treatment with corticosteroids. turk j med sci. 2017;47(5):1590-1592. doi:10.3906/sag-1611-100 5. atak t, sagiroglu j, eren t, ali özemir i, alimoglu o. strategies to treat idiopathic granulomatous mastitis: retrospective analysis of 40 patients. breast dis. 2015;35(1):19-24. doi:10.3233/bd-140373 6. çetin k, sıkar he, güllüoğlu bm. idiopathic granulomatous mastitis with erythema nodosum: is it a variant of clinical presentation indicating treatment resistance? a retrospective cohort study. breast j. 2020;26(9):1645-1651. doi:10.1111/tbj.13944 7. vural s, ertop p, ceyhan k, şanli h. an unusual cause of oligoarthritis and erythema nodosum: idiopathic granulomatous mastitis. arch rheumatol. 2017;32(1):71-75. doi:10.5606/archrheumatol.2017.5952 8. bes c, soy m, vardi s, sengul n, yilmaz f. erythema nodosum associated with granulomatous mastitis: report of two cases. rheumatol int. 2010;30(11):15231525. doi:10.1007/s00296-009-1109-y 9. gümüş m, akkurt zm, gümüş h. is erythema nodosum coexisting with lesions of the breast a suggestive sign for idiopathic granulomatous mastitis? turk j surg. 2018;34(1):71-73. doi:10.5152/turkjsurg.2017.3161 10. polat m, kaya h. plantar erythema nodosum associated with granulomatous mastitis. indian j dermatol venereol leprol. 2016;82(2):202-204. doi:10.4103/0378-6323.164219 11. kalaycı tö, koruyucu mb, apaydın m, etit d, varer m. idiopathic granulomatous mastitis associated with erythema nodosum. balk med j. 2016;33(2):228-231. doi:10.5152/balkanmedj.2015.150089 12. parperis k, achilleos s, costi e, vardas m. granulomatous mastitis, erythema nodosum and arthritis syndrome: case-based review. rheumatol int. 2021;41(6). doi:10.1007/s00296-021-04820-8 13. lucas r, gussman d, polis rl, rattigan mi, matulewicz tj. idiopathic granulomatous mastitis with erythema nodosum simulating breast abscess in pregnancy: a case report. obstet med. 2014;7(1):3739. doi:10.1177/1753495x13502474 14. zabetian s, friedman bj, mchargue c. a case of idiopathic granulomatous mastitis associated with erythema nodosum, arthritis, and reactive cough. jaad case rep. 2016;2(2):125-127. doi:10.1016/j.jdcr.2016.01.011 15. fruchter r, castilla c, ng e, pomeranz mk, femia an. erythema nodosum in association with idiopathic granulomatous mastitis: a case series and review of the literature. j eur acad dermatol venereol. 2017;31(9):e391-e393. doi:10.1111/jdv.14194 16. adams dh, hubscher sg, scott dg. granulomatous mastitis--a rare cause of erythema nodosum. postgrad med j. 1987;63(741):581-582. doi:10.1136/pgmj.63.741.581 17. weber j, gros d, blaison g, martin t, storck d, pasquali j. mastite granulomateuse, érythème noueux et oligoarthrite. à propos d’une observation. rev médecine interne. 1994;15(3):190-192. doi:10.1016/s0248-8663(05)82147-2 18. olfatbakhsh a, beheshtian t, djavid ge. granulomatous mastitis, erythema nodosum, and oligoarthritis in a pregnant woman. breast j. 2008;14(6):588-590. doi:10.1111/j.15244741.2008.00653.x 19. goldberg j, baute l, storey l, park p. granulomatous mastitis in pregnancy. obstet gynecol. 2000;96(5, part 2):813-815. doi:10.1016/s0029-7844(00)01051-6 20. alungal j, abdulla mc, narayan r. idiopathic granulomatous mastitis with erythema nodosum and polyarthritis. reumatismo. 2016;68(2):97-99. doi:10.4081/reumatismo.2016.844 21. choi ec, wong sbj, ho s-aj. idiopathic granulomatous mastitis and erythema nodosum – a unifying pathophysiology? australas j dermatol. 2021;62(1):e149-e153. doi:10.1111/ajd.13463468138.12604 22. binesh f, shiryazdi m, bagher owlia m, azimi s. idiopathic granulomatous mastitis, erythema nodosum and bilateral ankle arthritis in an iranian woman. bmj case rep. 2013;2013. doi:10.1136/bcr-2012-007636 23. koksal h. human leukocyte antigens class i and ii in patients with idiopathic granulomatous mastitis. am j surg. 2019;218(3):605-608. doi:10.1016/j.amjsurg.2019.01.038 24. koksal h, vatansev h, artac h, kadoglou n. the clinical value of interleukins-8, -10, and -17 in idiopathic granulomatous mastitis. clin rheumatol. 2020;39(5):1671-1677. doi:10.1007/s10067-020-049258 25. saydam m, yilmaz kb, sahin m, et al. new findings on autoimmune etiology of idiopathic granulomatous mastitis: serum il-17, il-22 and il-23 levels of patients. j invest surg. published online february 11, 2020:1-5. doi:10.1080/08941939.2020.1725190 26. nakamura t, yoshioka k, miyashita t, et al. granulomatous mastitis complicated by arthralgia and skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 99 erythema nodosum successfully treated with prednisolone and methotrexate. intern med tokyo jpn. 2012;51(20):2957-2960. doi:10.2169/internalmedicine.51.7846 27. kruse n, greif m, moriabadi nf, marx l, toyka kv, rieckmann p. variations in cytokine mrna expression during normal human pregnancy. clin exp immunol. 2000;119(2):317-322. doi:10.1046/j.13652249.2000.01123.x 28. hida t, minami m, kawaguchi h, oshiro y, kubo y. case of erythema nodosum associated with granulomatous mastitis probably due to corynebacterium infection. j dermatol. 2014;41(9):821-823. doi:10.1111/13 29. al-khaffaf bh, shanks jh, bundred n. erythema nodosum – an extramammary manifestation of granulomatous mastitis. breast j. 2006;12(6):569-570. doi:10.1111/j.1524-4741.2006.00348.x 30. salesi m, karimifar m, salimi f, mahzouni p. a case of granulomatous mastitis with erythema nodosum and arthritis. rheumatol int. 2011;31(8):1093-1095. doi:10.1007/s00296-009-1273-0 31. jacquin-porretaz c, devalland c, delapparent t, nardin c, dupond a-s. [idiopathic granulomatous mastitis associated with erythema nodosum]. ann dermatol venereol. 2019;146(8-9):571-576. doi:10.1016/j.annder.2019.04.023 32. donn w, rebbeck p, wilson c, gilks cb. idiopathic granulomatous mastitis. a report of three cases and review of the literature. arch pathol lab med. 1994;118(8):822-825. skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 794 research letter melasma is associated with lower serum vitamin d concentrations as compared to healthy controls laura andrews, mscr1, chelsea shope, mscr1, ansley devore, bs1, lara wine lee, md, phd2,3, carol l. wagner, md3 1 college of medicine, medical university of south carolina, charleston, sc 2 department of dermatology, medical university of south carolina, charleston, sc 3 department of pediatrics, medical university of south carolina, charleston, sc abstract background: melasma is a common, chronic skin condition of hyperpigmentation involving the appearance of symmetric and irregular light brown macules and patches, mainly on sun exposed skin of the head and neck. though the pathogenesis is not fully understood, hyperfunctional melanocytes are known to deposit excess melanin in the epidermis and dermis. vitamin d has been shown to influence melanogenesis via its influence on the vitamin d receptor. due to the avoidance of ultraviolet light recommended to patients with melasma, vitamin d supplementation is recommended. given the known influence of vitamin d on the skin, and the large prevalence of melasma in the public, the association between vitamin d and melasma will be examined further. methods: a retrospective review was performed utilizing the trinetx platform to query deidentified patient data from the medical university of south carolina’s electronic health record system over a 9-year period from january 2013 to may 2022. calcidiol (25-hydroxyvitamind) was utilized as a surrogate for vitamin d level. statistical analyses were performed using t-testing. results: of 1,962 patients diagnosed with melasma, 840 had a serum calcidiol level measured following diagnosis. the majority of these patients were female (77%) and had an average age of 60.3 + 19.2 years. melasma patients were most commonly caucasian (81%), followed by african american (15%) and hispanic or latino (3%). patients with melasma had an average serum calcidiol of 33.8 + 15.8 ng/ml (reference range: 25 – 80 ng/ml). this was significantly lower than comparison to 2,146 dermatology patients not diagnosed with melasma (36.8 + 15.8 ng/ml, p-value <0.0001%). conclusion: vitamin d has been demonstrated to be critical in the skin, including differentiation and proliferation of melanocytes. our results suggest that patients with melasma, who have significantly lower levels of serum vitamin d than their healthy counterparts, may benefit from vitamin d supplementation. future studies investigating improvement in melasma symptoms following vitamin d supplementation are needed. skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 795 melasma is a common, chronic skin condition of hyperpigmentation involving the appearance of symmetric and irregular light brown macules and patches on sun exposed skin.1-3 melasma affects 5-6 million women in the us, including 50-70% of pregnant women.2 though the pathogenesis is not fully understood, hyperfunctional melanocytes are known to deposit excess melanin in the epidermis and dermis.2 vitamin d has been shown to stimulate melanogenesis, and to regulate the activation, proliferation, and migration of melanocytes. vitamin d deficiency has a prevalence of 40% in the us, with the highest rates seen in african americans (82.1%) and hispanic (69.2%) patients.2,4 melasma is also disproportionately prevalent in those with fitzpatrick skin types iv-vi, making it a common problem experienced by african american, hispanic, and asian populations.2 common treatments include avoidance of uv light.3 it is due to this avoidance of uv light that vitamin d supplementation is recommended, though the susceptibility of patients with higher fitzpatrick skin types to develop vitamin d deficiency should also be considered.5 this is especially true given that these higher skin types are prone to develop melasma. due to the known influence of vitamin d on melanocytes,6 and the high prevalence of both melasma and vitamin d deficiency, we aimed to further examine the association between vitamin d status and melasma. after receiving irb approval, a retrospective review was performed utilizing the trinetx platform to query de-identified patient data from january 2013 may 2022. serum calcidiol (25-hydroxy-vitamin d) concentration was utilized to indicate vitamin d status. statistical analyses were performed using t-testing. of 1,962 patients diagnosed with melasma, 840 had a serum calcidiol level measured following diagnosis. most patients were female (77%) with a mean age of 60.3 + 19.2 years. melasma patients were caucasian (81%), followed by african american (15%) and hispanic or latino (3%). patients with melasma had an average serum calcidiol of 33.8 + 15.8 ng/ml (range: 3.2 – 101) (reference range: 25 – 80 ng/ml). this was significantly lower in comparison to 1,044 ethnicity and sex matched controls (36 + 15.3 ng/ml, range: 2.5 – 149.6, p-value <0.0270) (table 1). table 1. patient demographics and calcidiol concentration. melasma patients control patients p-value number of patients 1,992 1,044 age (years)1 60.2 ± 19.2 64.7 ± 15.2 <0.0001 sex2 female 1,530 (77%) 833 (80%) 0.602 male 462 (23%) 211 (20%) 0.602 ethnicity2 hispanic or latino 41 (2%) 13 (1%) 0.1074 not hispanic or latino 1,936 (97%) 1,022 (98%) 0.2442 unknown 15 (1%) 10 (1%) 0.5530 serum calcidiol1,3 33.8 ± 15.9 (range 3.2101) 36.0 ± 15.3 (range 2.5 – 149.6) 0.0270 1mean ± sd 2count (%) 3reference rage: 25–80ng/ml vitamin d is known to have major influence in the skin.6 it enacts its effects via the vitamin d receptor (vdr). this receptor is expressed in both melanocytes and keratinocytes, with the highest level of vdr expression is at the skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 796 basal layer of the epidermis.1,6 activation of vdr causes inhibition of growth of both normal and malignant melanocytes.1 epidermal proliferation and differentiation also occurs via vdr in keratinocytes.6 it has also been suggested that vdr may influence androgen and estrogen activation, which are proposed to play a role in the pathogenesis of melasma.1 given this understanding of the vdr, one would expect vitamin d levels to be normal or even elevated in patients with melasma, a disease characterized by overactive melanocytes, and that is especially prevalent in pregnant women. however, patients in our cohort had significantly lower levels of serum calcidiol. our results are consistent with a 2018 study that also observed a significant correlation between melasma and low serum calcidiol levels.7 this expected pattern may differ for individuals who receive little to no sun exposure or consistently utilize sun protective measures. to date, no studies have investigated changes in melasma symptoms with vitamin d supplementation. however, the significantly lower serum calcidiol levels observed in the melasma cohort underscores the need to provide vitamin d supplementation to such patients, given that avoidance of uv light remains a treatment of choice.8 melasma is a common condition with significant impact on quality of life due to the emotional and psychosocial consequences of its physical symptoms.2 vitamin d has been demonstrated to be critical in the skin, with involvement in the differentiation and proliferation of melanocytes. our results suggest that patients with melasma may benefit from vitamin d supplementation. larger, multi-center studies investigating the correlation between serum calcidiol and melasma, and future studies exploring changes in melasma symptoms following vitamin d supplementation, are warranted. conflict of interest disclosures: none funding: none corresponding author: carol l. wagner, md medical university of south carolina 10 mcclennan banks drive, msc 915 charleston, sc usa 29425 phone: 843-792-2112 email: wagnercl@musc.edu references: 1. seleit i, bakry oa, masoud e, nabil s. identification of genotypes and allelic frequencies of vitamin d receptor gene polymorphism (taqi) in egyptian melasma patients. indian dermatol online j. 2017;8(6):443-448. 2. ortonne jp, arellano i, berneburg m, et al. a global survey of the role of ultraviolet radiation and hormonal influences in the development of melasma. j eur acad dermatol venereol. 2009;23(11):1254-1262. 3. grimes pe. melasma. etiologic and therapeutic considerations. arch dermatol. 1995;131(12):1453-1457. 4. forrest ky, stuhldreher wl. prevalence and correlates of vitamin d deficiency in us adults. nutr res. 2011;31(1):48-54. 5. becker s, schiekofer c, vogt t, reichrath j. [melasma : an update on the clinical picture, treatment, and prevention]. hautarzt. 2017;68(2):120-126. 6. piotrowska a, wierzbicka j, żmijewski ma. vitamin d in the skin physiology and pathology. acta biochim pol. 2016;63(1):1729. 7. chaitanya nc, priyanka dr, madireddy n, et al. melasma associated with periodontitis, anemia, and vitamin d abnormalities: a chance occurrence or a syndrome. j contemp dent pract. 2018;19(10):12541259. 8. mckesey j, tovar-garza a, pandya ag. melasma treatment: an evidence-based review. am j clin dermatol. 2020;21(2):173225. skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 811 brief article five years later: continuing disparity in the geographic density and distribution of u.s. dermatologists christopher n. nguyen, md1, quoc-bao nguyen, md, mba2,3, kyle lauck, md4, adelaide hebert, md2,3 1department of internal medicine, northside hospital gwinnett, lawrenceville, ga 2department of dermatology, the university of texas md anderson cancer center, houston, tx 3department of dermatology, uthealth mcgovern medical school, houston, tx 4department of internal medicine, uthealth mcgovern medical school, houston, tx despite expansion of the dermatologic workforce, a discrepancy remains in the geographical distribution of dermatologists across the united states (us). from a 2014 american academy of dermatology (aad) survey, dermatologists in rural areas were more likely to report an undersupply of dermatologists, while dermatologists in urban areas were more likely to report an oversupply.1 the glazer et al. studies analyzing the geographic distribution of practicing dermatologists in the us in 2009 and 2016 confirmed this maldistribution.2,3 this study presents a continuation of those studies and aims to reexamine the current geographical density of dermatologists to describe any changes that may have occurred over the past 5 and 12 years, respectively. abstract objectives: a discrepancy exists in the geographical distribution of dermatologists across the united states (us). the aim of this study was to reexamine the current geographical density of dermatologists to describe any changes compared to date from 5 and 12 years ago. methods: membership data from the 2021 american academy of dermatology (aad) database were retrieved to characterize the distribution of dermatologists in 3-digit zip code areas. results: out of 712 populated zip codes with dermatologists, 510 (71.6%) had less than 4 dermatologists per 100,000, as compared to 515 (72.3%) in 2016 (– 0.19% cagr). the dermatologist density of the 100 most populated areas (m = 4.5 dermatologists per 100,000, sd = 3.3) and 100 least populated areas (m = 1.6 dermatologists per 100,000, sd = 6.2) were significantly different (p < 0.0001). conclusion: this analysis provides continued trends to compare to previous studies performed in 2016 and 2009. the highest and lowest density areas were similar to results from previous studies. the results indicate an enduring and significant maldistribution of dermatologists in the us. introduction methods skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 812 like the previous studies, de-identified data for aad members were retrieved from the most current aad membership database, the 2021 aad membership database for this analysis. demographic information included the member’s category, state, and zip code. fellows were included as practicing dermatologists. us territories were excluded from this analysis. us population data was obtained from the american community survey. information associated with 5-digit zip codes were consolidated to their corresponding larger 3-digit zip codes. compound annual growth rates (cagr) were calculated to assess annual percentage growth. and descriptive statistics and unpaired two-sample t-tests were used. institutional review board approval was not necessary as no human subjects were used for this study. the 2021 database contained 11,525 dermatologists compared with 10,845 in 2016 (1.22% cagr) and 9,598 in 2009 (1.54% cagr). with the u.s. population approaching 328 million, there are 3.5 dermatologists per 100,000 people, an increase from 3.4 in 2016 (0.58% cagr) and 3.2 in 2009 (0.75% cagr). there were 712 zip codes that were populated and had at least 1 dermatologist; 510 (71.6%) of them had less than 4 dermatologists per 100,000, as compared to 515 (72.3%) in 2016 (– 0.19% cagr). there were 174 areas that were populated (average population of 99,000) but had no dermatologists at all. the dermatologist density of the 100 most populated areas (m = 4.5 dermatologists per 100,000, sd = 3.3) and 100 least populated areas (m = 1.6 dermatologists per 100,000, sd = 6.2) were significantly different (p < 0.0001). the 10 highest and lowest dermatologist density locations from the current analysis and the 2016 analysis are listed (figure 1 and figure 2). this listing is based on locations that have at least 1 dermatologist. the average density for the 10 densest locations was 24.6 dermatologists per 100,000, an increase from 23.3 in 2016 (1.1% cagr), but a decrease from 25 in 2009 (– 0.13% cagr). and 83.5% of the dermatologists in the top 10 areas practice in the northeast. specifically, 93% can be found in either manhattan or boston. currently, 36.5% of dermatologists practice in the 100 densest areas, a downtrend from 38.6% in 2016 (– 1.11% cagr) and 40% in 2009 (– 0.76% cagr). conversely, only 1.6% of dermatologists practice in the 100 least dense areas as compared to 1.8% in 2016 (– 2.33% cagr). our analysis reveals an enduring maldistribution of dermatologists between urban and rural areas (figure 3). almost 20% of populated zip codes did not have a single dermatologist. like in 2009, the 10 densest zip codes had an average density 7 times the national average. also, 9 of the 10 densest zip codes in 2016 remained among the top 10 in 2021. none of the least dense areas in 2016 improved to more than 1 dermatologist per 100,000. some suggest that 4 dermatologists per 100,000 people is the ratio needed to sufficiently care for a population.3 consistent with 2016, over 70% of areas do not meet that target density and nearly 60% have less than 3 per 100,000. in the past 5 years, only 5 more zip codes reached this threshold. these results may indicate that initiatives aimed at redistribution of dermatologists have not made a major difference. results discussion skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 813 figure 1. comparison of the 10 most dermatologist-dense areas, for locations with at least 1 dermatologist, in the united states in 2021 vs 2016. skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 814 figure 2. comparison of the 10 least dermatologist-dense areas, for locations with at least 1 dermatologist, in the united states in 2021 vs 2016. skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 815 figure 3. us dermatologist density by 3-digit zip code. the number of dermatologists practicing per 100,000 people in each 3-digit zip code is indicated by the colors on the map. zip codes without any dermatologists are included in white. addressing underserved areas remains paramount as dermatologist density is associated with patient outcomes, particularly in melanoma and merkel cell carcinoma.4,5 multiple solutions have been considered. one of the strongest barriers in rural physician retention is lack of geographical connection, partly due to the limited residency positions available. partnerships between residency programs and rural hospitals may expand residency spots, while also supporting underserved areas.6 advanced practice practitioners may alleviate rural areas, however, they tend to favor urban areas as well.7 and teledermatology has proven to be effective in rural communities, with reimbursement constraints as the greatest barrier.8 other strategies to consider include financial incentives, increasing physician spouse job opportunities, and recruiting students of rural backgrounds. this study is limited by the aad membership database, as aad membership distribution may not represent the true distribution of all us dermatologists. however, this analysis may still add to the overall discussion and provide insight into the subject, since we used a consistent methodology as previous studies and present trends over a 5and 12year span. another limitation is our analysis assumes each area requires similar a dermatologist density (4 dermatologists per skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 816 100,000 people) and we cannot account for specific differences in demand within each area. the data presented constitutes one metric and should be interpreted alongside other measures of adequacy (such as appointment wait-times) for a holistic viewpoint of this nuanced issue. based on the aad membership database, an enduring maldistribution of dermatologists exists. this complex issue likely needs a multifaceted solution with continual effort and thought from leaders in the field. recurrent assessment of the database in the future can continue to help identify areas that may be underserved. this knowledge may provide insight into the effectiveness and implementation of countermeasures and, ultimately, improve patient care and outcomes. conflict of interest disclosures: none funding: none corresponding author: christopher n. nguyen, md 1 baylor plaza houston, tx 77030 email: christopher.nguyen42@gmail.com references: 1. ehrlich a, kostecki j, olkaba h. trends in dermatology practices and the implications for the workforce. j am acad dermatol. 2017;77(4):746-752. doi:10.1016/j.jaad.2017.06.030 2. yoo jy, rigel ds. trends in dermatology: geographic density of us dermatologists. arch dermatol. 2010;146(7):779. doi:10.1001/archdermatol.2010.127 3. glazer am, farberg as, winkelmann rr, et al. analysis of trends in geographic distribution and density of us dermatologists. jama dermatol. 2017;153(4):322-325. doi:10.1001/jamadermatol.2016.5411 4. aneja s, aneja s, bordeaux js. association of increased dermatologist density with lower melanoma mortality. arch dermatol. 2012;148(2):174-178. doi:10.1001/archdermatol.2011.345 5. criscito mc, martires kj, stein ja. a populationbased cohort study on the association of dermatologist density and merkel cell carcinoma survival. j am acad dermatol. 2017;76(3):570572. doi:10.1016/j.jaad.2016.10.043 6. feng h, berk-krauss j, feng pw, et al. comparison of dermatologist density between urban and rural counties in the united states. jama dermatol. 2018;154(11):1265–1271. doi:10.1001/jamadermatol.2018.3022 7. coustasse a, sarkar r, abodunde b, et al. use of teledermatology to improve dermatological access in rural areas. telemed j e health. 2019;25(11):1022-1032. doi:10.1089/tmj.2018.0130. epub 2019 feb 11. pmid: 30741608. 8. adamson as, suarez ea, mcdaniel p, leiphart pa, zeitany a, kirby js. geographic distribution of nonphysician clinicians who independently billed medicare for common dermatologic services in 2014. jama dermatol. 2018;154(1):30-36. doi:10.1001/jamadermatol.2017.5039 conclusion health disparities in melanoma patients: understanding the influence of comorbidities on overall survival among our poorest patient populations amanda rosenthal, md1; joanie chung, mph2; robert cooper md3; reina haque, phd2,4; christina kim, md1 1 department of dermatology, kaiser permanente los angeles medical center, los angeles, ca; 2 department of research & evaluation, kaiser permanente southern california; kaiser permanente los angeles medical center (th), pasadena, ca; 3 department of pediatric hematology/oncology, southern california permanente medical group, kaiser permanente los angeles medical center, los angeles, ca; 4 department of health systems science, kaiser permanente bernard j. tyson school of medicine, pasadena, ca no authors have any financial relationships to disclose. conclusion • we demonstrate an 18% increased risk of death among our poorest melanoma patients that cannot be explained by an increased comorbidity burden. • given that all patients included in this analysis had health insurance coverage within the same vertically integrated healthcare system, in which barriers to care are minimized, we must identify the other factors influencing mortality risk among our poorest melanoma patients. • some possible, modifiable behaviors that we hope to explore in the future include lack of follow up and surveillance allowing for close monitoring, as well as implicit bias and cultural preferences guiding treatment options offered, accepted, and utilized. synopsis • the incidence and prevalence of modifiable comorbidities is known to vary by measures of socioeconomic status (ses), with an excess burden appreciated among lower socioeconomic groups.1,2 • it is established that both lower ses and an increased comorbidity burden result in poorer health outcomes.3 • we hypothesized and demonstrated that both lower ses and higher numbers of modifiable comorbidities, as defined by the elixhauser comorbidity index (eci), negatively influences all-cause mortality in patients diagnosed with melanoma. • specifically, we find that the survival disparity appreciated among melanoma patients of lower ses is persistent, albeit attenuated, even when adjusting for the presence of comorbidities, as defined by the eci. objective to evaluate the influence of ses on all-cause mortality in a population of insured melanoma patients within kaiser permanente southern california’s (kpsc) integrated healthcare system, while adjusting for the presence of comorbid conditions. methods results references 1. pathirana ti, jackson ca. socioeconomic status and multimorbidity: a systematic review and meta-analysis. australian and new zealand j pub health 42(2):186-94, 2018. 2. tucker-seeley rd, li y, sorensen g, subramanian sv. lifecourse socioeconomic circumstances and multimorbidity among older adults. bmc public health 11(313), 2011. 3. rosenthal a, reddy s, chung j, kim c, cooper r, haque r. disparities in overall survival in patients with melanoma by race/ethnicity, socioeconomic status, and healthcare systems. skin (manuscript submitted for publication november 2021). retrospective cohort study design kpsc cancer registry 2010-2018 diagnosis of stage i-iv melanoma 7,993 melanoma cases 1,243 all-cause deaths analysis by cox proportional models hazard ratios (hr) for the association between all-cause mortality and ses, adjusted for the presence of modifiable comorbidities (as determined by eci) 0 200 400 600 800 1000 1200 1400 1600 1800 2000 0 1 2 3 4 5+ melanoma diagnoses and total deaths by number of comorbidities as defined by eci* melanoma diagnoses total deaths 1 1.5 2 lowest ses lower-middle ses middle ses upper-middle ses highest ses hazard ratios for all-cause mortality adjusted model 1: hr adjusted for all sociodemographic variables (including ses), and not eci adjusted model 2: hr adjusted for all sociodemographic variables (including ses) and eci n um be r of c as es *eci: elixhauser comorbidity index number of comorbidities by eci skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 100 original research exploring the psychosocial impact on parents of adolescents diagnosed with hidradenitis suppurativa: a retrospective claimsbased analysis jay yang, bs1, joslyn s kirby, md, ms, med1, steven maczuga, ms1 1 department of dermatology, penn state college of medicine, hershey pa hidradenitis suppurativa (hs) is a chronic skin condition that causes painful lumps and nodules to form on the body, mainly affecting folds of the body such as the groin and axilla1. the exact prevalence remains unclear but seems to be anywhere between 0.05 – 4% depending on the source, with significant variations in prevalence reported in different countries, populations, and study designs1-3. hs is often diagnosed in the 3rd or 4th decade of life, but there is often a 3to 12-year diagnostic delay, with a mean delay of 7.2 years4. hs is a chronic inflammatory condition that can be exacerbated by various familial and environmental factors abstract background: chronic conditions, such as hidradenitis suppurativa (hs), can have an immense impact on patient quality of life; however, less is known about the influence that these diseases may have on the parents of adolescent patients with hs. this study aims to investigate the significance of an hs diagnosis on an adolescent’s parents, including depression, anxiety, and changes in employment status. an understanding of this relationship can assist in both the prevention, screening, and treatment of mental health conditions in parents. methods: this retrospective cross-sectional analysis was conducted using data from the marketscan claims database. data were collected for adolescents and their parents using a 3-year study period between 1/1/2015-12/31/2017; families with adolescents aged 11-17 years with hs and randomly selected age-/sex-matched adolescents without hs and their families (1:5 ratio) were used as controls, and a total of 20,568 families were included in this study. claims of depression, anxiety, and employment status change in parents of adolescents with hs were compared against parents of adolescents without hs using regression analysis. results: the study population involved 20,568 families, including 3,428 families with hs (mean [sd] age of adolescent: 14.54 [1.70]) and 17,140 control families (mean [sd] age of adolescent: 14.35 [1.92]). the majority of adolescents in the study were female (81.7%). parents of adolescents with hs experienced significantly higher rates of depression (21.53% vs. 19.57%, p = 0.009) than unaffected parents, as well as significantly higher rates of employment status change (6.30% vs 5.21%, p = 0.01). conclusions: parents of adolescents with hs are more likely to experience depression and changes in employment status than unaffected parents. these results highlight the significant consequences that an hs diagnosis has on a family and underscore the need for further attention and resources for the mental health of these susceptible caregivers. introduction skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 101 including smoking, obesity, and genetic mutations1-3. the resultant effect is a heavy disease burden on both the patient and potentially also on the patient’s providers and caregivers. hs has a negative impact on patient qualify of life. studies have shown that patients with hs experience both severe physical and psychological symptoms5,6. these detrimental consequences of hs are often due to active lesions, but can also be attributed to chronic damage from past inflammation, leading to continued distress5. additionally, quality of life surveys of hs patients consistently show that hs patients suffer from impaired quality of life compared to non-hs patients, and score worse in domains such as pain, embarrassment, psychological distress, intimate relationships, etc.6. hs patients also consistently endure higher rates of depression, anxiety, and suicidality than non-hs patients, highlighting the adverse mental-health implications of hs7. while the detrimental impacts of an hs diagnosis on the patients themselves have been welldocumented, less is known about how an hs diagnosis affects the patient’s family members. in a cross-sectional study exploring the impact of psoriasis in adolescents on their families, psoriasis was found to affect the quality of life of families even in cases of mild disease8. in another study involving parents of children with psoriasis, psoriasis was shown to negatively impact all parents interviewed, with the greatest effect on emotional well-being, among other domains9. in addition to the mental-health influence of psoriasis on caregivers, the severity of psoriasis was also found to be negatively correlated with the financial status of psoriasis patients and their families, contributing to reduced quality of life as well10. together, these studies suggest a significant burden associated with an adolescent’s psoriasis on multiple domains of the parent’s life. a systematic review that analyzed the disease loads of both atopic dermatitis and psoriasis on their families substantiated these results, finding that childhood atopic dermatitis also appeared to negatively impact maternal physical and mental well-being, while furthermore inducing feelings of exhaustion, frustration, helplessness, etc.11. psoriasis had similar effects, with emotional wellness being an area of substantial impact. despite these findings regarding other dermatologic conditions in adolescents, we are not aware of any studies on the impact of hs in an adolescent on a parent. a better understanding of this relationship may help to guide future interventions targeted at this population while contributing to the growing knowledge base surrounding this complex disease. thus, this novel study examines the impact of an hs diagnosis on an adolescent’s parents, including mental health issues and work-related disruptions. this is a retrospective cross-sectional analysis of de-identified claims data obtained from the ibm marketscan commercial claims database. the database contains a wide array of medical claims data for over 265 million patients. these data include health insurance claims across the continuum of care (e.g. inpatient, outpatient, outpatient pharmacy, carve-out behavioral healthcare) from large employers and health plans across the united states. selection criteria a 3-year study period was used (january 1, 2015 – december 31, 2017; these were the most recent complete years of data available at the time). families with methods skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 102 adolescents aged 11-17 years with hs were identified using icd-9/10 codes for hs (705.83 and l73.2, respectively), and randomly selected age-/sex-matched adolescents without hs and their families (1:5 ratio) were used as controls. parents were linked to their children using a unique family id in the marketscan database, and if a family had multiple children, only the oldest child was included. only those with continuous enrollment during this time were included. additionally, parents who were younger than the adolescent’s age + 18 years were also excluded from the study; this was due to the nature of the deidentified data possibly coding for these family members as “parents” when they may just be siblings. demographic information, prevalence of depression or anxiety (new or existing), employment status, and changes in employment status were collected. depression was defined as icd-9 codes 296.2, 296.3, 300.4, 301.1, or 311, and icd10 codes f320, f321, f322, f323, f324, f325, f329, f330, f331, f332, f333, f3341, f3342, f339, f340, f341, f6089. anxiety was defined as icd-9 codes 300.0x, and icd-10 codes f410, f411, f418, f419. employment status change was defined as a change from active full-time to active parttime/seasonal, retirement, or disability. depression/anxiety diagnoses before or after the hs diagnosis were combined since hs was likely present in the patient prior to the actual date of hs diagnosis (as outlined previously) and had already begun affecting both the patient and the patient’s family. statistical analysis descriptive statistics and regression analysis were conducted using sas version 9.4. differences between the hs and control group outcome variables were analyzed using the χ2 test, and p-values were calculated. when the univariate analysis was significant for hs, a multivariate logistic regression model was then created for each of the desired outcome variables (depression, anxiety, employment status). the independent variables included in the logistic regression models were parental hs status, adolescent sex, parental sex, parental age, parental obesity, and child’s hs status. this study was approved by the penn state college of medicine institutional review board. cohort statistics this study included 20,568 families; 3,428 in the hs group and 17,140 in the control group (table 1). the majority of adolescents in both the hs group and control group were female (81.71% and 81.74%, respectively). approximately half of the parents were female in both the hs group and control group (53.93% and 52.16%, respectively). notably, 3.2% of parents in the hs cohort also had a diagnosis of hs compared to 0.3% in the control group. in the hs group, 76.2% of parents were employed full-time, compared to 79.71% of parents in the control group. finally, in the hs group, 47.49% of the parents were obese, while only 31.46% of the parents in the control group were obese. this disparity will be addressed later in the discussion section. depression table 2 shows a comparison of the frequency of parental depression for the hs and control groups, as well as a logistic regression analysis using the variables in table 1 as predictors of depression. the rate of parental depression was significantly higher in the hs group than in the control group (21.53% vs. 19.57%, p = 0.009). results skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 103 roughly equal proportions of female adolescents were seen in both the overall cohort and the depression cohort (~82%); however, there was a much higher proportion of female parents with depression than there were female parents in the overall cohort (69% vs. 52%, p < 0.0001). after adjusting for parental sex, parental age, parental hs status, parental obesity, and change in employment status, the presence of hs in the adolescent was not a significant predictor (or: 1.06 (95% ci: 0.98, 1.16), p = 0.15) of depression in the parent(s). of these variables, parental sex and parental obesity were found to be significant predictors of hs status. anxiety table 3 presents a comparison of the hs and control groups for families related to anxiety. overall, there were no significant differences between the hs and control families. employment status table 4 displays a comparison between the hs and control groups for families who experienced a change in employment status. the rate of employment status change was significantly greater for hs families than for control families (6.30% vs 5.21%, p = 0.01). notably, this difference primarily impacted a single parent rather than both parents. regression analysis shows that after adjusting for parental sex, parental age, parental hs status, parental obesity, depression, anxiety, and adolescent sex, the presence of hs in the adolescent contributed to a higher odds (or: 1.17 (95% ci: 1.02, 1.34), p = 0.021) of employment change in the parent(s). parental obesity, depression, anxiety, and parental age were all significant predictors of hs status. in this large retrospective claims-based study, parents of adolescents affected by hs were found to be at higher risk for enduring both depression and changes in employment status. while overall anxiety rates were slightly higher in parents of adolescents with hs than parents of adolescents without hs, these differences were not significant. parents of adolescents with hs experienced significantly higher rates of depression in the univariate analysis than parents of adolescents without hs. most of the disparity between the hs and control groups for depression came from one parent being affected. it should also be noted that these results held even when factoring in the higher proportion of parents with hs in the hs group than the control group, and parental hs status was not a significant predictor in the logistic regression model. in the multivariate analysis controlling for parental sex, parental age, parental hs status, parental obesity, and change in employment status, adolescent hs status was no longer found to be a significant predictor of parental depression. of the above variables, parental obesity was the most significant predictor of parental depression, with obese parents having much higher odds of being depressed than nonobese parents. parental obesity may serve as a mediating variable, where the stress of an adolescent having hs leads to a parent becoming obese and depressed. additionally, depression seems to more heavily affect mothers than fathers, as evidenced by the higher percentage of female parents represented in the depression cohort as compared with the percentage of female parents in the overall cohort (69% vs. 52%, p < 0.0001). this discussion skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 104 conclusion is supported by the logistic regression analysis showing that parental sex was a significant predictor for depression, with fathers having substantially lower odds of developing depression (or: 0.45 (95% ci: 0.42, 0.48), p < 0.001). these table 1. descriptive statistics for families with or without an adolescent affected by hs hs in adolescent group control group total number of families 3,428 17,140 one parent enrolled 1,191 4,787 two parents enrolled 2,237 12,353 number of parents with hs 110 52 adolescent age, mean (sd) 14.54 (1.70) 14.35 (1.92) adolescent sex, n (%) male 627 (18.29%) 3,130 (18.26%) female 2,801 (81.71%) 14,010 (81.74%) parent age, mean (sd) 45.48 (6.26) 45.58 (6.26) parent sex, n (%) male 2,610 (46.07%) 14,109 (47.84%) female 3,055 (53.93%) 15,384 (52.16%) parent is obese 1,628 (47.49%) 5,393 (31.46%) table 2. odds of parental depression for families with or without an adolescent affected by hs hs in adolescent group (n = 3,428) control group (n = 17,140) p-value or (ci), p-value* number of affected families, n (% of total cohort) 738 (21.53%) 3,355 (19.57%) 0.009 hs present in adolescent: 1.06 [0.98, 1.16], 0.15 one affected parent 661 (19.28%) 3,008 (17.55%) 0.02 two affected parents 77 (2.25%) 347 (2.02%) 0.40 adolescent sex, n (%) male 123 (16.69%) 587 (17.50%) 0.60 0.94 [0.86, 1.02], 0.16 female 614 (83.31%) 2,768 (82.50%) 1.0 [ref] parent sex, n (%) male 239 (29.33%) 1,144 (30.90%) 0.38 0.45 [0.42, 0.49], <0.0001 female 576 (70.67%) 2,558 (69.10%) 1.0 [ref] age of parent, mean (sd) 46.26 (6.26) 45.71 (6.47) 25-40, n (%) 147 (18.04%) 801 (21.63%) 0.02 1.00 [0.86, 1.17], 0.97 41-55, n (%) 611 (74.97%) 2,642 (71.35%) 0.04 0.86 [0.75, 0.99], 0.038 >55, n (%) 57 (6.99%) 260 (7.02%) 0.98 1.0 [ref] parent is obese 1.81 [1.69, 1.95], <0.0001 *multivariate logistic regression included parental hs status, child’s hs status, parental age, parental sex, adolescent sex, and employment status change. ci: 95% confidence interval skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 105 table 3. odds of parental anxiety for families with or without an adolescent affected by hs hs in adolescent group (n = 3,428) control group (n = 17,140) p-value number of affected families, n (% of total cohort) 906 (26.43%) 4,434 (25.87%) 0.49 one affected parent 787 (22.96%) 3,921 (22.87%) 0.92 two affected parents 119 (3.47%) 513 (2.99%) 0.14 adolescent sex, n (%) male 161 (17.79%) 837 (18.88%) 0.44 female 744 (82.21%) 3,597 (81.12%) parent sex, n (%) male 309 (30.15%) 1,632 (32.99%) 0.08 female 716 (69.85%) 3,315 (67.01%) age of parent, mean (sd) 45.68 (6.09) 45.55 (6.31) 25-40, n (%) 219 (21.37%) 1,088 (21.99%) 0.66 41-55, n (%) 739 (72.10%) 3,562 (71.99%) 0.94 >55, n (%) 67 (6.64%) 298 (6.02%) 0.53 table 4. odds of parental change in employment for families with or without an adolescent affected by hs hs in adolescent group (n = 3,428) control group (n = 17,140) p-value or (ci), p-value* number of affected families, n (% of total cohort) 216 (6.30%) 893 (5.21%) 0.01 hs present in adolescent: 1.17 [1.02, 1.34], 0.021 one affected parent 139 (4.05%) 508 (2.96%) <0.001 two affected parents 77 (2.25%) 385 (2.25%) 1 adolescent sex, n (%) male 39 (18.06%) 168 (18.81%) 0.80 1.01 [0.89, 1.15], 0.87 female 177 (81.94%) 725 (81.19%) 1.0 [ref] parent sex, n (%) male 130 (44.37%) 580 (45.38%) 0.75 0.95 [0.86, 1.06], 0.36 female 163 (55.63%) 698 (54.62%) 1.0 [ref] age of parent, mean (sd) 46.32 (6.79) 46.77 (6.76) 25-40, n (%) 69 (23.55%) 247 (19.33%) 0.10 0.51 [0.42, 0.63], <0.0001 41-55, n (%) 199 (67.92%) 903 (70.66%) 0.36 0.52 [0.44, 0.63], <0.0001 >55, n (%) 25 (8.53%) 128 (10.02%) 0.44 1.0 [ref] parent is obese 1.32 [1.18, 1.49], <0.0001 number of parents with concurrent depression, n (%) 58 (26.85%) 259 (29.00%) 0.53 1.46 [1.27, 1.68], <0.0001 number of parents with concurrent anxiety, n (%) 69 (31.94%) 330 (36.95%) 0.17 1.44 [1.27, 1.65], <0.0001 *multivariate logistic regression included parental hs status, child’s hs status, parental age, parental sex, adolescent sex, parental depression, parental anxiety, and employment status change. ci: 95% confidence interval skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 106 findings are generally consistent with the global trend of the incidence of depression being 1.7-fold greater in women than men12. this is meaningful from a clinical perspective as it helps clinicians recognize that mothers of adolescents with hs may be at increased risk for depression; thus, mental health screenings and counseling should be emphasized in this group. this is also consistent with past studies reporting that other dermatologic conditions such as atopic dermatitis and psoriasis harm maternal physical and mental well-being, and induce feelings of exhaustion, frustration, helplessness, etc.11. a similar study using the marketscan database found that parents of children with autism spectrum disorder (asd) were significantly more likely to carry a diagnosis of depression than parents of children without asd, with mothers being at higher risk13. therefore, more focus should be placed on interventions aimed at addressing the mental health of these parents. in addressing mental-health needs in parents of adolescents with asd, recommended practice guidelines include dialoguing with other parents in similar situations, engaging in self-reflection, improving problem-solving abilities, and finding purpose in one’s life, all under the guidance and support of a physician14. similar guidelines could be beneficial in supporting parents of adolescents with hs. in addition to the mental health effects, parents of adolescents with hs also faced higher rates of employment status change than parents of adolescents without hs, and our logistic regression model, following adjustment, showed that adolescent hs status was associated with a significant increase in change from active full-time employment to active part-time/seasonal, retirement, or disability even when accounting for obesity, depression, and anxiety, as shown by the results in table 4. again, parental hs status was not a significant predictor for employment status, despite the higher proportion of parents with hs in the hs group than the control group. similar to the regression model for depression, parental obesity was the most significant predictor of employment status change; obese parents were much more likely to experience employment status changes than their non-obese counterparts. moreover, the entirety of the difference between the hs and control groups for employment status change could be seen from one parent being affected (4.05% vs. 2.96%, p < 0.001), suggesting that hs primarily impacts the employment of a single parent rather than both parents in a household. previous studies have reported a similar impact of chronic inflammatory conditions in children on parents’ work status. a marketscan study done by rasu et. al. found that parents of children with juvenile idiopathic arthritis (jia) missed 2.78 times more hours of work compared to the parents of children without jia15. while there were no significant differences observed in the univariate analysis of parental age groups for employment status change, this was still a significant variable in the logistic regression model. younger parents were less likely to experience a change in employment, as shown by the odds ratios for both parents aged 25-40 (or = 0.51, p < 0.0001) and 41-55 (or = 0.52, p < 0.0001) compared to 55+. thus, the importance of addressing the mental health of these parents cannot be understated. there are certain limitations to the results of this study. while some confounders such as age and sex were accounted for, other factors such as race/ethnicity and economic status were not adjusted for, as these variables were not available in the marketscan database. while obesity was skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 107 included in the regression analysis, there was a large disparity in the percentage of parents with obesity in the hs cohort compared to the control cohort, so future studies aim for more similar obesity rates between the two groups. additionally, given the nature of the study and the ibm marketscan database, diagnoses of neither hs nor depression/anxiety could be clinically confirmed. another drawback of the marketscan database is that it is limited to those with private insurance, thus excluding those without health insurance as well as those who may have lost health insurance through unemployment. another limitation of the marketscan database was the inability to confirm the role of the person in the family (i.e. mother, father), and thus does not account for the psychosocial impact on mothers vs. fathers in single-parent families. to prevent siblings from being accidentally coded as parents, “parents” who were younger than their adolescent’s age + 18 years were removed from the study, but this may have unintentionally included/excluded some patients. additionally, diagnoses of depression and anxiety were limited to those cases that were reported on a claim, so overall depression and anxiety may be underestimated due to cases being unreported. finally, in this study, cases of incident and prevalent depression/anxiety were combined into one group; however, as previously stated, due to the frequency of delay in diagnosing hs, this appeared plausible to do. our study indicates that parents of adolescents with hs are significantly more likely to either have or be diagnosed with depression than unaffected parents. this disparity is mainly seen in parents under the age of 55. while parents of adolescents with hs experience higher rates of depression, only parental sex and parental obesity are significant predictors for odds of depression. furthermore, parents of adolescents afflicted by hs are significantly more likely to experience a change in employment status than unaffected parents, with parental obesity and hs status being significant predictors. taken altogether, this study shows that hs is a disease that affects not only the quality of life of the patient but also the patient’s caregivers; thus, more attention and resources, for both prevention and intervention, should be given to the mental health of these parents. the disease burden of hs extends beyond just the patients themselves, so it is important to have communication and discussions with family members around the difficulties of an hs diagnosis in their loved ones and identify those who are struggling early on. conflict of interest disclosures: none funding: none data availability statement: all data generated or analyzed during this study are included in this article. further enquiries can be directed to the corresponding author. corresponding author: joslyn sciacca-kirby, md, ms, med department of dermatology milton s hershey penn state medical center 500 university dr, hu 14 hershey, pa 17033 office: 717-531-8307 fax: 717-531-6516 email: jkirby1@hmc.psu.edu references: 1. napolitano m, megna m, timoshchuk e, et al. hidradenitis suppurativa: from pathogenesis to diagnosis and treatment. clinical, cosmetic and investigational dermatology. 2017;volume 10:105-115. doi:10.2147/ccid.s111019. conclusion skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 108 2. phan k, charlton o, smith sd. global prevalence of hidradenitis suppurativa and geographical variation—systematic review and meta-analysis. biomedical dermatology. 2020;4(1). doi:10.1186/s41702-019-0052-0 3. miller im, mcandrew rj, hamzavi i. prevalence, risk factors, and comorbidities of hidradenitis suppurativa. dermatologic clinics. 2016;34(1):7-16. doi:10.1016/j.det.2015.08.002 4. saunte d, boer j, stratigos a, et al. diagnostic delay in hidradenitis suppurativa is a global problem. british journal of dermatology. 2015;173(6):1546-1549. doi:10.1111/bjd.14038 5. kirby js. qualitative study shows disease damage matters to patients with hidradenitis suppurativa. journal of the american academy of dermatology. 2016;74(6):12691270. doi:10.1016/j.jaad.2016.01.001 6. mahon jm, kirthi s, byrne n, o'grady c, tobin a. an update on health-related quality of life and patient-reported outcomes in hidradenitis suppurativa. patient related outcome measures. 2020;volume 11:21-26. doi:10.2147/prom.s174299 7. patel kr, lee hh, rastogi s, et al. association between hidradenitis suppurativa, depression, anxiety, and suicidality: a systematic review and metaanalysis. journal of the american academy of dermatology. 2020;83(3):737-744. doi:10.1016/j.jaad.2019.11.068 8. salman a, yucelten ad, sarac e, saricam mh, perdahli-fis n. impact of psoriasis in the quality of life of children, adolescents and their families: a cross-sectional study. anais brasileiros de dermatologia. 2018;93(6):819823. doi:10.1590/abd1806-4841.20186981. 9. tollefson mm, finnie dm, schoch jj, eton dt. impact of childhood psoriasis on parents of affected children. journal of the american academy of dermatology. 2017;76(2). doi:10.1016/j.jaad.2016.09.014. 10. hawro t, zalewska a, hawro m, kaszuba a, królikowska m, maurer m. impact of psoriasis severity on family income and quality of life. journal of the european academy of dermatology and venereology. 2014;29(3):438-443. doi:10.1111/jdv.12572. 11. na ch, chung j, simpson el. quality of life and disease impact of atopic dermatitis and psoriasis on children and their families. children. 2019;6(12):133. doi:10.3390/children6120133. 12. albert p. why is depression more prevalent in women? journal of psychiatry & neuroscience. 2015;40(4):219-221. doi:10.1503/jpn.150205. 13. cohrs ac, leslie dl. depression in parents of children diagnosed with autism spectrum disorder: a claims-based analysis. journal of autism and developmental disorders. 2017;47(5):1416-1422. doi:10.1007/s10803017-3063-y. 14. catalano d, holloway l, mpofu e. mental health interventions for parent carers of children with autistic spectrum disorder: practice guidelines from a critical interpretive synthesis (cis) systematic review. international journal of environmental research and public health. 2018;15(2):341. doi:10.3390/ijerph15020341. 15. rasu rs, cline sk, shaw jw, hayes o, bawa wa, cifaldi ma. impact of jia on parents’ work absences. rheumatology. 2014;54(7):1177-1185. doi:10.1093/rheumatology/keu414. acknowledgements: medical writing support was provided by prescott medical communications group (chicago, il) with financial support from ortho dermatologics; ortho dermatologics is a division of bausch health us, llc • presented at the 2022 fall clinical dermatology conference • october 20-23, 2022 • las vegas, nv synopsis � truncal acne (occurring on the chest and back) is common among patients with facial acne,1-3 though its pathophysiology may be somewhat different4,5 � as there are no specific guidelines for the treatment of truncal acne, facial acne treatment guidelines are often the basis for its management3 � successful treatment of truncal acne is complicated by the involvement of a large body surface area that is typically covered in clothing3 � topical vehicles that provide ease of spreadability, rapid cutaneous penetration/effective drug delivery, and lack of residue are highly desirable for truncal acne treatment1 � a lower-dose tazarotene 0.045% lotion formulation (arazlo®; ortho dermatologics) was developed utilizing polymeric emulsion technology (figure 1)6 • this highly spreadable lotion formulation was developed to allow for more efficient delivery of tazarotene into dermal layers • in phase 1 studies, this lotion demonstrated low irritation/contact dermatitis potential and no allergic sensitization7 objectives � to evaluate tazarotene 0.045% lotion on the trunk using three studies with distinct objectives: • study 1: summarize the efficacy, safety, and tolerability of tazarotene 0.045% lotion in the treatment of truncal acne • study 2: compare the irritation potential with repeated application of tazarotene 0.045% lotion and trifarotene 0.005% cream on the trunk • study 3: evaluate the spreadability of tazarotene 0.045% lotion and trifarotene 0.005% cream on the trunk figure 1. polymeric emulsion technology for tazarotene 0.045% lotion 1-2 μm ① polymeric matrix holds water and water-soluble hydrating agents within a 3-d mesh ② droplets of tazarotene and oil-soluble moisturizing agents held apart by the 3-d mesh ③ 3-d mesh allows for uniform distribution of tazarotene and moisturizing agents study 2: irritation potential tazarotene 0.045% lotion vs trifarotene 0.005% cream • modi�ed cumulative irritancy patch test in 20 healthy adults (22–74 years; fitzpatrick skin types i-ii) • patches loaded with tazarotene 0.045% lotion, trifarotene 0.005% cream, or control (no product) were applied to the upper back; patches replaced every 2–3 d for 12 d • after each patch removal, skin was assessed for dermal effects (eg, erythema, edema, papules) and other effects (eg, glazing, peeling, cracking) on a scale of 0 to 7 study 2 design a. dermal effects 0.0 1.5 2.0 2.5 3.0 day 1 day 3 day 5 day 8 m e a n s co re , d e rm a l r e sp o n se 1.0 tazarotene 0.045% lotion trifarotene 0.005% cream control *p<0.05; **p<0.01; ***p≤0.001 vs tazarotene 0.045% lotion. #p<0.05; ##p<0.01; ###p<0.001 active drug vs control. • over 12 days of exposure, tazarotene 0.045% lotion was associated with minimal irritation • tazarotene 0.045% lotion was signi�cantly less irritating than trifarotene 0.005% cream 2 days after �rst patch application and continuing through day 12 0.5 day 10 day 12 3=erythema and papules 2=de�nite erythema, readily visible; minimal edema/ papular response 1=minimal erythema; barely perceptible b. other effects 0.0 1.5 2.0 2.5 3.0 day 1 day 3 day 5 day 8 m e a n s co re , o th e r e ff e ct s 1.0 0.5 day 10 day 12 3=glazing with peeling and cracking 2=marked glazing 1=slight glazed appearance ### ### ## ***###***### ***### ***### *# ***###**### **###**## ******** tazarotene 0.045% lotion trifarotene 0.005% cream control study 3: spreadability tazarotene 0.045% lotion vs trifarotene 0.005% cream9 ***p<0.001 vs trifarotene 0.005% cream. • double-blind split-body study of 30 healthy adults (18–59 years) • each product (0.1 ml) was applied to a 10 cm wide area on one side of subjects’ backs and moved down the back until it would no longer spread; area of spread was then determined 160 0 40 80 120 167.0 tazarotene 0.045% lotion m e a n a re a o f p ro d u ct s p re a d ( cm 2 ) 130.3 200 trifarotene 0.005% cream tazarotene 0.045% lotion trifarotene 0.005% cream mean spreadability of tazarotene lotion and trifarotene cream (n=30) subject example mean difference: 36.7 cm2 • on average, skin coverage with tazarotene 0.045% lotion was ~30% greater than with trifarotene 0.005% cream study 3 design tazarotene 0.045% lotion for truncal acne: efficacy, tolerability, and spreadability leon h kircik, md1-3; zoe d draelos, md4; eric guenin, pharmd, phd, mph5 1icahn school of medicine at mount sinai, new york, ny; 2indiana university medical center, indianapolis, in; 3physicians skin care, pllc, dermresearch, pllc, and skin sciences, pllc, louisville, ky; 4dermatology consulting services, pllc, high point, nc; 5ortho dermatologics*, bridgewater, nj *ortho dermatologics is a division of bausch health us, llc study 1: efficacy, safety, and tolerability in truncal acne tazarotene 0.045% lotion8 • subjects aged ≥12 years • moderate truncal acne (investigator’s global assessment score = 3) • once-daily treatment with tazarotene 0.045% lotion for 12 weeks • age (mean): 24.1 years • sex: 52.6% female • race: 52.6% white, 36.8% black, 10.5% biracial study 1 design demographics total lesion reductions -100% -60% -40% -20% 0% baseline week 4 week 8 week 12 ls m e a n p e rc e n t c h a n g e f ro m b a se lin e -80% -44.9% *** tazarotene 0.045% lotion (n=19) -67.7% *** -82.3% *** ls mean percent changes from baseline: il -49.4%*** -63.8%*** -83.3%*** nil -7.6%* -59.3%** -64.3%** cutaneous tolerability and safety 0% 40% 60% 80% 100% p e rc e n ta g e o f s u b je ct s 20% there were no adverse events related to tazarotene treatment in this study. bl, baseline. clear/almost clear skin 0% 40% 60% 80% 100% baseline week 4 week 8 week 12 p e rc e n ta g e o f s u b je ct s 20% *** 21% tazarotene 0.045% lotion (n=19) *** 47% *** 89% truncal ef�cacy *p<0.05; **p<0.01; ***p<0.001 vs baseline. il, in�ammatory lesions; ls, least squares; nil, nonin�ammatory lesions. severity: none trace mild 11% 90% 100% peeling bl 11% 16% 74% 5% 21% 74% erythema 11% 90% 100% dryness 95% 5% 95% oiliness 5% 16% 84% 11% 5% 84% pruritus 5% 95% 11% 5% 84% burning at week 12: • ~90% achieved clear or almost clear skin • >80% reductions from baseline in total lesion counts • most subjects had no tolerability issues • there were no signi�cant changes from baseline to week 12 in any tolerability assessment wk12 bl wk12 bl wk12 bl wk12 bl wk12 bl wk12 conclusions � tazarotene 0.045% lotion utilizes polymeric emulsion technology to enhance hydration, moisturization, and skin barrier function � tazarotene 0.045% lotion led to statistically significant reductions in truncal acne severity and lesion counts; ~90% of subjects achieved clear or almost clear skin with 12 weeks of once-daily use and most subjects had no tolerability issues � this easy-to-apply tazarotene lotion was associated with less irritation and ~30% greater skin coverage compared with trifarotene cream • less product needed to cover the same skin area equals more applications per unit volume references 1. del rosso jq. cutis. 2006;77:285–289. 2. dréno b, et al. jeadv. 2015;29(6):1096–1106. 3. poli f, et al. jeadv. 2020;34(10):2241–2246. 4. short rw, et al. pediatr dermatol. 25(1):126–128. 5. kim br, et al. dermatol. 231:87–93. 6. tanghetti ea, et al. j dermatol treat. 2019;sept 26:1–8. 7. kircik lh, et al. j dermatol treat. 2021;aug 30:1–9. 8. kircik lh. j drugs dermatol. 2022;21(7):713–716. 9. draelos zd, et al. j drugs dermatol. 2021;21(3):250–257. author disclosures leon h kircik has acted as an investigator, advisor, speaker, and consultant for ortho dermatologics. zoe d draelos received funding from ortho dermatologics to conduct the research presented here. eric guenin is an employee of ortho dermatologics and may hold stock and/or stock options in its parent company. microsoft word 14. 653 proof done.docx skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 82 brief articles dural-based metastatic malignant melanoma masquerading as meningiomata: a diagnostic challenge mina zarei, md,1 mahtab forouzandeh, bs,1 jennifer ledon, md,1 george w elgart, md,1 jeong hee cho-vega, md, phd2 1 department of dermatology and cutaneous surgery, university of miami miller school of medicine, miami, florida, usa 2 department of pathology, dermatopathology, sylvester comprehensive cancer center, miller school of medicine, university of miami, miami, fl, usa metastases from malignant melanomas (mm) to the dura mater are exceedingly rare and have been described in only a handful of reports, a majority of which are autopsy studies.1 mm metastases to the central nervous system are more commonly represented by secondary lesions in the brain parenchyma or leptomeninges, rather than in the dura.2 meanwhile, metastatic lesions in the dura mater arise most commonly from carcinomas of the prostate, lungs, and breasts.3 unfortunately, these intracranial lesions can often times appear indistinguishable from meningiomas on imaging, leading to misdiagnoses and significant treatment delays. because patients with metastatic disease require prompt oncological intervention, it is imperative for physicians to consider the possibility of metastases when evaluating dural masses. regrettably, dural metastatic disease is one of the least studied patterns of neoplastic spread, underscoring the importance of an interdisciplinary diagnostic approach.4 introduction metastases from malignant melanomas can be difficult to diagnose, particularly when they are in uncommon locations. we report on an unsettling case of a 38-year-old woman who presented to neurosurgery with worsening neurological symptoms. upon magnetic resonance imaging (mri), the patient was found to have two sizeable dural-based lesions and underwent subsequent resection of the larger mass. although the results of the pathohistological examination and immunohistochemistry staining were suspicious for metastatic malignant melanoma, an incorrect diagnosis of atypical meningioma was rendered due to the patient’s age and lack of melanoma history. after the patient’s condition continued to clinically deteriorate, dermatology was ultimately consulted and a more comprehensive work-up was carried out, revealing the correct and exceedingly rare diagnosis of dural-based metastatic melanoma of unknown primary. this case underscores the importance of a comprehensive diagnostic approach; one which employs careful histopathologic evaluation, judiciously selected immunohistochemical staining, and thorough physical examination. abstract skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 83 we report on a 38-year-old woman who presented to neurosurgery with sudden leftsided deafness, facial droop and gait dysfunction. mri revealed a large left petrotentorial mass (3.5 x 3.7 x 2.6 cm) with enhancement heterogeneity and a dural tail (figure 1). an additional smaller dural mass, with similar radiographic features, was found adjacent to the right temporal lobe. the larger mass was resected and histopathological examination revealed cells with eosinophilic cytoplasm and intranuclear inclusions, as well as abundant tumor necrosis and increased mitotic activity. on immunohistochemistry, tumor cells were focally positive for ki-67 and ema, diffusely positive for melan-a, hmb45, s100, and ecadherin, weakly positive for ssrt2 and sox-10, and negative for ck7. a diagnosis of atypical meningioma, oncocytic variant, was favored due to radiographic findings, poor tumor differentiation, patient age, and lack of melanoma history. several weeks later, the patient returned with worsening neurological symptoms. mri revealed a dramatic interval increase in size of the second tumor with surrounding vasogenic edema. the patient subsequently underwent resection of this mass, and upon discovery of a malignant epithelioid tumor on frozen section, dermatology was consulted. concurrently, mutation sequencing of the initial petrotentorial mass was revealed to be braf p.v600e positive. on physical exam, multiple firm, painless subcutaneous nodules and tumors (≤ 8 cm) were appreciated, with no atypical nevi or cutaneous ulcerations noted. punch biopsy revealed malignant epithelioid cells positive for sox10 and pan melanoma (hmb-45, melan-a, tyrosinase), while negative for h3k27me3 and ck7 (figure 2). a positronemission tomography scan uncovered numerous hypermetabolic subcutaneous lesions. given the similar histology and immunophenotype expressed by the subcutaneous and dural tumors, a new diagnosis of dural-based metastatic melanoma of unknown primary was made. the patient was promptly started on treatment with dabrafenib and trametinib in combination with whole-brain radiation therapy. figure 1. parts a-b magnetic resonance imaging of the brain (a) t2-weighted axial imaging shows a 3.5 x 3.7 x 2.6 cm enhancing extra-axial, multilobulated mass with dural tail, located in the left posterior fossa. (b) t1-weighted post-contrast coronal imaging shows the left petrotentorial mass causing mass effect on the brainstem, fourth ventricle, and left middle cerebellar peduncle. figure 2. parts a-d punch biopsy of right abdominal nodule (4 mm wide x 1 mm in depth) (a) staining with hematoxylin and eosin (h&e) shows pleomorphic epithelioid cells with vesicular nuclei and prominent eosinophilic nucleoli (original magnification x200). (b) immunohistochemical stain (ihc) is positive for sox-10, a marker for melanocytic cell differentiation (original magnification, x4).(c) ihc stain is positive for pan melanoma cocktail (hmb45, mart-1, tyrosinase), supporting the diagnosis of metastatic melanoma (original magnification, x4). (d) ihc stain for h3k27me3 is retained, ruling out report of a case skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 84 malignant peripheral nerve sheath tumor (original magnification, x4). despite both clinical and radiographic examination, dural-based lesions from metastatic carcinomas, such as mm, are particularly susceptible to misdiagnoses. while imaging studies are helpful in evaluating brain lesions, they can also be misleading; of note, the “dural-tail,” a radiographic sign traditionally considered a characteristic feature of meningiomas, can also be seen in dural-based metastatic carcinomas.1,3 similarly, clinical evaluation and patient history may fail to provide evidence of a primary malignancy, as seen in this case. thus, physicians should avoid diagnosing dural-based lesions as benign tumors solely based on clinical and radiographic judgment; a diagnosis of “meningioma” in this limited setting should be approached with clinical suspicion and pursuit of histopathologic differential diagnoses. this case highlights that, while patient history, physical examination and radiographic imaging are important, judicious histopathologic evaluation combined with carefully selected immunohistochemical staining are essential to the accurate and timely diagnosis of dural-based metastatic malignant melanomas, as well as other duralbased lesions. keywords: malignant melanoma; dermatopathology; immunohistochemistry; metastatic melanoma; meningioma; dural-based metastatic carcinoma; intracranial lesions conflict of interest disclosures: none funding: none corresponding author: mahtab forouzandeh, bs university of miami miller school of medicine dr. phillip frost department of dermatology and cutaneous surgery 1295 nw 14th st suite k/l/m miami, fl 33136 tel: 502-759-7691 email: m.forouzandeh@umiami.edu references: 1. barajas rf jr, cha s. metastasis in adult brain tumors. neuroimaging clin n am. 2016;26(4):601–620. doi:10.1016/j.nic.2016.06.008 2. nayak l, abrey le, iwamoto fm. intracranial dural metastases. cancer. 2009;115:1947–1953. 3. savage nm, alleyne ch, vender jr, et al. duralbased metastatic carcinomas mimicking primary cns neoplasia: report of 7 cases emphasizing the role of timely surgery and accurate pathologic evaluation. int j clin exp pathol. 2011;4(5):530– 540. 4. scherer k, johnston j, panda m. dural based mass: malignant or benign. j radiol case rep. 2009;3(11):1–12. doi:10.3941/jrcr.v3i11.189 discussion skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 292 short communications herpes simplex masquerading as bacterial lymphangitis pooja r. shah, md1, fatema s. esaa, ba2, lisa a. beck, md1 1department of dermatology, university of rochester medical center, rochester, ny 2university of rochester school of medicine and dentistry, rochester, ny a 46-year old healthy caucasian female with a history of crohn’s disease (currently in remission) presented to the emergency department with a 2-week history of painful and pruritic rash affecting the right 5th finger, upper extremity, and neck. pruritis began initially ten days prior to presentation. subsequently, three days prior to presentation, patient experienced sudden onset pain and erythema of the right 5th finger with progression along her right forearm. she noted that her symptoms were worsening but was not able to identify any alleviating or aggravating factors. extensive review of systems was otherwise negative, except for lymphadenopathy. she denied recent travel or exposure to raw foods, poison ivy, rose bushes, rodents, or new medications; however, she noted that she lived in a barn and had direct contact with horses, cats, and dogs. physical exam was notable for a very painful, ulcerated pink plaque with serosanguinous crust and surrounding erythema with few pustules at the periphery on the right anterior neck. on the right distal dorsal 5th finger, there was a hemorrhagic bulla with prominent erythema accompanied by a linear erythematous streak extending proximally (figure 1 a-c). she had painful enlarged lymph nodes in her right submandibular and axillary regions. the patient was treated empirically with oral clindamycin and azithromycin for possible bacterial infection, resulting in only partial clinical response. there was significant reduction in erythema and pain, but persistent itch and burning. figure 1. (a) on physical exam there was a very painful, ulcerated pink plaque with serosanguinous crust and surrounding erythema and peripheral pustules on the right anterior neck. a skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 293 (b) on the right distal dorsal 5th finger, there was a hemorrhagic bulla with prominent erythema. (c) accompanied by a linear erythematous streak extending proximally. cbc, cmp, and esr were unremarkable. chest x-ray was negative. bacterial culture from the finger lesion was positive for 3+ mssa and non-hemolytic streptococcus. viral pcr from finger lesion was positive for hsv1. bartonella serology was negative. the patient subsequently responded very well to oral valacyclovir with complete resolution. lymphangitis is inflammation along the lymphatic channels that occurs as a result of infection at a distal site, most commonly observed in the setting of acute bacterial infections such as group a betahemolytic streptococcus, staphylococcus aureus, pseudomonas, and pasteurella multicoda. consequently, the presence of lymphangitic streaking often results in treatment with systemic antibiotics. however, superficial lymphangitis may also occur secondary to nonbacterial etiologies including viral or fungal infections, arthropod bites, or iatrogenic interventions.1 although the natural history of herpes simplex lymphangitis is self-resolution, antiviral therapy may shorten the duration of symptoms and help prevent recurrence.2 our patient demonstrates a unique case of cutaneous herpes simplex infection with centrifugal spread complicated by lymphangitis and regional lymphadenopathy. awareness of nonbacterial causes of lymphangitis will help prevent misdiagnosis, unnecessary antibiotic use, and the delay of appropriate treatment. conflict of interest disclosures: none funding: none corresponding author: pooja r. shah, md university of rochester medical center department of dermatology 601 elmwood ave, po box 697 rochester, ny 14642 email: pshah12@northwell.edu references: 1. cohen, b.; nagler, a., & pomeranz, m. (2016) nonbacterial causes of lymphangitis with streaking, journal of the american board of family medicine, 29 (6). 2. sands m, brown r. herpes simplex lymphangitis: two cases and a review of the literature. arch intern med. 1988;148(9):2066– 2067. doi:10.1001/archinte.1988.00380090126029 b c mailto:pshah12@northwell.edu mailto:pshah12@northwell.edu skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 341 short communication clinicopathologic correlation: differentiating between localized lichen myxedematosus and scleromyxedema kamran k. harper, md1, lauryn m. falcone md, phd1, kevin t. savage, md1, alaina j. james, md, phd1 1 university of pittsburgh department of dermatology/upmc, pittsburgh, pa scleromyxedema, also known as sclerodermoid or generalized lichen myxedematosus, is a rare type of primary cutaneous dermal mucinosis associated with monoclonal gammopathy, systemic symptoms, and normal thyroid studies.1 clinically, scleromyxedema can have a variable presentation with potential for relapse. histologically, scleromyxedema can be indistinguishable from localized lichen myxedematosus (lm).2 unlike patients with lm, patients with scleromyxedema may develop severe complications such as dermato-neuro syndrome, which is a potentially fatal condition characterized by a flu-like prodrome followed by fever, seizures, and coma.3 it is important to differentiate scleromyxedema from lm early due to the risk of progressive systemic disease. ivig is generally regarded as first-line therapy for scleromyxedema. second line-agents include thalidomide or lenalidomide paired with systemic glucocorticoids. melphalan, bortezomib with dexamethasone, or autologous hematopoietic stem cell transplantation can be utilized for severe or refractory disease.4 we report the case of a 38-year-old female with chronic arthritis who presented with an 11-month history of biopsy-proven lm that was recalcitrant to treatment with topical steroids and methotrexate. on physical exam, she had numerous, 2mm, monomorphic, dome-shaped papules on the lateral cheeks, upper dorsolateral arms, and anterior legs. repeat punch biopsy of the right upper arm demonstrated increased mucin deposition separating thickened collagen fibers and increased fibroblasts in the superficial dermis consistent with “scleromyxedema/lichen myxomatous.” upon further review of her medical records, our patient had a history of epilepsy and monoclonal igg gammopathy. given the patient’s constellation of symptoms and prior medical history, she was diagnosed with scleromyxedema. we referred her to oncology and began treatment with ivig, after which she experienced an improvement in symptoms and complete resolution of her skin lesions. within 5 months of discontinuing ivig, our patient’s skin disease relapsed. on repeat examination, she had scattered 2mm domeshaped papules on the dorsal hands similar to her prior presentation. she also had scattered 5-8mm faintly violaceous macules on the upper and lower dorsal extremities. biopsies of both lesion types revealed mildly skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 342 increased fibroblasts and dermal mucin, reconfirming the diagnosis of scleromyxedema. our patient is scheduled to reinitiate ivig therapy with the goal of achieving clearance of her skin lesions. in the absence of long-term, continuous treatment, scleromyxedema has the potential to progress and evolve clinically.4 scleromyxedema can be distinguished from lm through careful history and physical exam. earlier correlation of this patient’s dermatologic presentation with her systemic signs including monoclonal gammopathy, epilepsy, and arthritis may have prompted sooner initiation of the appropriate treatment for scleromyxedema. given that prognosis and management of lm and scleromyxedema differ, patients with histologic evidence of a cutaneous mucinosis should be screened for evidence of systemic involvement. conflict of interest disclosures: none funding: none corresponding author: alaina j. james, md, phd university of pittsburgh department of dermatology/upmc 3601 fifth avenue suite 5a, pittsburgh, pa, 15213 email: jamesaj@upmc.edu references: 1. rongioletti f, rebora a. updated classification of papular mucinosis, lichen myxedematosus, and scleromyxedema. j am acad dermatol. 2001;44(2):273-281. doi:10.1067/mjd.2001.111630 2. rongioletti f, merlo g, carli c, et al. histopathologic characteristics of scleromyxedema: a study of a series of 34 cases. j am acad dermatol. 2016;74(6):1194-1200. doi:10.1016/j.jaad.2015.12.021 3. fleming ke, virmani d, sutton e, et al. scleromyxedema and the dermato-neuro syndrome: case report and review of the literature. j cutan pathol. 2012;39(5):508-517. doi:10.1111/j.1600-0560.2012.01882.x 4. knobler r, moinzadeh p, hunzelmann n, et al. european dermatology forum s1-guideline on the diagnosis and treatment of sclerosing diseases of the skin, part 2: scleromyxedema, scleredema and nephrogenic systemic fibrosis. journal of the european academy of dermatology and venereology. 2017;31(10):1581-1594. doi:10.1111/jdv.14466 mailto:harperkk@upmc.edu photodynamic therapy for facial actinic keratosis with aminolevulinic acid 10% gel, microneedling, and red-light illumination ziv schwartz, md, mha department of dermatology and cutaneous biology sidney kimmel medical college at thomas jefferson university philadelphia, pa gary goldenberg, md assistant clinical professor, dermatology icahn school of medicine at mount sinai hospital new york, ny email: garygoldenbergmd@gmail.com synposis photodynamic therapy (pdt) treats both visible actinic keratosis (ak) lesions and field cancerization. drug delivery via topical ala has limited penetration through the skin. the present study evaluated aesthetic improvement, ak clearance, pain during treatment, and adverse events in five subjects treated by pdt with microneedling-assisted delivery of 10% ala gel and red-light illumination. aesthetic appearance was much improved to very much improved at 4 and 8 weeks, respectively; the mean ak clearance was 89.2% at 8 weeks; red light illumination was well tolerated, and adverse events were not observed. background chronic sun exposure may result in actinic keratosis (ak) with malignant potential. photodynamic therapy (pdt) treats both visible ak lesions and field cancerization. in pdt, a photosensitizing agent (5-aminolevulinic acid, ala) is topically applied to the treatment area and selectively taken up by the target cells. drug delivery via topical ala has limited penetration through the skin, so microneedling has been used to facilitate deeper penetration. objective the present study evaluates the efficacy and safety of pdt using microneedling-assisted delivery of 10% ala nanoemulsion gel (biofrontera, woburn, ma) with 30-minute incubation followed by red-light illumination (biofrontera, 635 nm, 37 j/cm2). methods a prospective 3-month study was conducted to evaluate aesthetic improvement and ak clearance relative to baseline in each of five subjects treated by pdt with microneedling-assisted delivery of 10% ala gel and red-light illumination. follow-up (fu) visits were made at weeks 1, 2, 4, and 8. five qualified subjects (aged 18-75 years, skin types i-iv) with 4 to 8 mild to moderate facial aks enrolled in the study and provided signed informed consent. the study outcome was used to set the foundation for future clinical trials. the primary endpoints were changes in subjectand investigator-graded global aesthetic improvement scale (gais) scores in which 3 = very much improved, 2 = much improved, 1 = improved, 0 = no change, -1 = worse, -2 = much worse, and -3 = very much worse. secondary endpoints were (1) ak clearance as quantified by count of aks at 8-week fu vs. baseline and (2) safety as measured by patient-reported pain on an 11-point visual analog scale (vas) (in which 0 = no pain, 5 = moderate pain, and 10 = worst pain) during red-light illumination and adverse events documented at the time of treatment and at each fu visit. results all five subjects completed the study. the mean gais scores are shown in figure 1. ak clearance (mean ± sd) at 8 weeks was 89.2 ± 14.9%. pain was well tolerated and mean pain score during illumination was 3.2 ± 1.6 on the 11-point vas. adverse events were not observed during the study. conclusion pdt using microneedling-assisted delivery of 10% ala nanoemulsion gel with 30-minute incubation followed by red-light illumination results in much improved to very much improved gais at 4 and 8 weeks, respectively; 89.2% ak clearance at 8 weeks; and tolerable pain during red light illumination. this study was investigator-initiated and funded by biofrontera inc. the authors have no financial relationships to disclose. figure 1. the mean subject and investigator global aesthetic improvement scale (gais) scores at follow-up visits. 3 = very much improved, 2 = much improved, 1 = improved, 0 = no change, -1 = worse, -2 = much worse, and -3 = very much worse. figure 2. clearance (%) of actinic keratosis (ak) lesions 8 weeks after microneedling-assisted photodynamic therapy (pdt). figure 3. subject-reported pain during illumination. subjects graded pain according to a vas score in which 0 = no pain, 5 = moderate pain, and 10 = worst pain. skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 834 brief article bazex syndrome associated with angioimmunoblastic t-cell lymphoma gregory ugoh, bs1, anthony linfante, md1, allison good, md1, janice wilson, md1, kathleen kroger, md1 1the university of texas medical branch at galveston, galveston, tx bazex syndrome was first described by bazex et al. in 1965 in association with malignancy of the upper aerodigestive tract.1 the main features are the presence of symmetrical psoriasiform eruptions, nail dystrophy, and xerotic scaling usually accentuated on the acral surfaces, ears, and nose.2 several mechanisms for development of bazex syndrome have been proposed. one theory suggests that antibodies against the tumor cross react with the keratinocytes or basement membrane leading to damage of the basal layer of the skin. alternatively, an immune reaction directed against tumor-like antigens in the epidermis could be responsible for the cutaneous eruptions. association with cutaneous squamous cell carcinoma, hodgkin’s disease, peripheral tcell lymphoma, and follicular lymphoma in situ have been reported.3 we present a unique case of bazex syndrome associated with aitl. to our knowledge, this is the first reported case of bazex syndrome seen in association with aitl. a 60-year-old male presented with a threemonth history of fever, diarrhea, xerosis, and a 20-lb weight loss. the patient reported a several-week history of a non-pruritic rash on his face and extremities. on physical exam, xerotic scaly plaques were noted on the ears, nose, and scalp, with ill-defined xerosis and adherent scale of the lower legs. desquamating keratoderma was seen on the palms, soles, and dorsal hands, along with beau’s lines of the fingernails abstract bazex syndrome, also known as acrokeratosis paraneoplastica, is a paraneoplastic disorder characterized by erythematous psoriasiform plaques involving the nose, ears, and acral sites. although classically associated with squamous cell carcinomas of the upper aerodigestive tract, it has also been reported in association with adenocarcinoma, genitourinary tumors, multiple myeloma, and rarely, peripheral t-cell lymphoma and follicular lymphoma in-situ. herein, we present a patient with bazex syndrome associated with angioimmunoblastic t-cell lymphoma (aitl), a rare association not previously reported in the literature. introduction case report skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 835 figure 1. (a) psoriasiform eruption of ear (b) beau’s lines on fingernails and scaling of hands (c) xerotic scaly plaques on plantar feet figure 2. h&e1 (20x): psoriasiform acanthosis with broad and blunt rete ridges, h&e 2 (200x): confluent parakeratosis and underlying hypogranulosis bilaterally (figure 1). diffuse lymphadenopathy was appreciated. ct scans revealed extensive lytic lesions throughout the spine, ribs, and scapula. lymphoma was suspected and a lymph node biopsy revealed aitl. a tangential biopsy and punch biopsy were performed, revealing psoriasiform acanthosis with broad and blunt rete ridges, along with hypogranulosis, confluent parakeratosis, and minimal inflammatory infiltrate (figure 2). the histological findings and clinical picture were consistent with bazex syndrome due to underlying aitl. the patient was then started skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 836 on topical steroids and urea with some improvement. however, the patient expired from angioimmunoblastic t-cell lymphoma shortly thereafter. bazex syndrome is a paraneoplastic disorder of the skin characterized by erythematous psoriasiform plaques in an acral distribution that classically also involve the nose and ears. histopathologic features of bazex syndrome are variable, but usually include acanthosis, hyperkeratosis, and parakeratosis. inconstant features include variable spongiosis and dyskeratosis.4-5 while the histologic features are not always diagnostic, the absence of diagnostic features of other conditions and clinicopathologic correlation are key to rule out other entities on the differential diagnosis. in our patient, the presence of confluent parakeratosis excluded the possibility of malignancyassociated ichthyosis. furthermore, the absence of other diagnostic features of psoriasis (i.e., neutrophilic microabscesses), in conjunction with the patient’s clinical presentation, excluded this possibility as well. the favored therapy for this paraneoplastic dermatosis is effective treatment of the underlying malignancy. for recalcitrant or palliative care, systemic treatments include corticosteroids, fluconazole, zinc, and cephalexin. topical treatments include retinoids, zinc ointment, puva, and emollients. although bazex syndrome is most commonly associated with squamous cell carcinoma of the upper aerodigestive tract, it has also been reported in association with adenocarcinoma, genitourinary tumors, and rarely, peripheral t-cell lymphoma and follicular lymphoma. herein, we present the first case of bazex syndrome seen in association with aitl. conflict of interest disclosures: none funding: none corresponding author: gregory ugoh ugoh the university of texas medical branch at galveston email: gaugoh@utmb.edu references: 1. humphrey sr, hussain as, chandran r, wilson b, george b. acute onset of acrokeratosis paraneoplastica (bazex syndrome). jama dermatol. 2015;151(6):677–678. doi:10.1001/jamadermatol.2014.5622 2. bazex a, salvador r, dupré a, et al. syndrome paranéoplasique à type d'hyperkératose des extrémités: guérison après le traitement de l'épithélioma laryngé. bull soc fr dermatol syphiligr. 1965;72:182. 3. santos-silva ar, correa mb, vargas pa, almeida op, lopes ma. bazex syndrome (acrokeratosis paraneoplastica) diagnosed in a patient with oral persistent ulcerations. head neck pathol. 2010;4(4):312-317. doi:10.1007/s12105-010-0203-5 4. eckstein j et al. a series of typical and atypical cases of bazex syndrome: identifying the red herring to avoid delaying cancer treatment. clin case rep. 2020;8(11):2259-2264. 5. publickal jk, kaliyadan f. acrokeratosis paraneoplastica. [updated 2020 may 24]. in: statpearls [internet]. treasure island (fl): statpearls publishing; 2021 jan-. available from: https://www.ncbi.nlm.nih.gov/books/nbk459391/ discussion the role of cutaneous microbiota harmony in maintaining a functional skin barrier h.e. baldwin1, n.d. bhatia2, a. friedman3, t. prunty4, r. martin5, s. seite6 abstract introduction the skin is constantly exposed to various endogenous and exogenous factors that may impact the barrier function at the physical, mechanical, and microbial levels. these factors have the potential to initiate or exacerbate a variety inflammatory skin conditions, especially those associated with barrier dysfunction. the barrier function of the skin depends upon a symbiotic relationship between resident microbial communities and host tissue. this symbiosis results from complex signals involved in both the innate and adaptive immune responses. recent research indicates that both bacterial diversity and the relative abundance of different microbes present on and in the skin may contribute to skin barrier stability of dysfunction. figure 1. current model of relationship between skin barrier and skin microbiota 1the acne treatment and research center of atlantic health system, morristown, nj 2therapeutics clinical research inc., san diego, ca 3george washington school of medicine and health sciences, washington, dc 4aramed strategies, de 5l’oréal research and innovation, tours, france 6la roche-posay dermatological laboratories, asnières, france human skin is a complex barrier organ that provides an ecological niche for a wide range of micro-organisms(1). the majority of these micro-organisms are harmless or beneficial, providing protection against pathogens and playing an important role in modulating the host’s cutaneous innate and adaptive immune systems(1). the skin is constantly exposed to factors (e.g., ultraviolet radiation, pollution, topical medications, skin care products) that can alter the balanced relationship between the skin and its microbiome(2). such disruption may result in increased risk for infections, chronic inflammatory skin disease (e.g., atopic dermatitis, psoriasis, rosacea, acne), and complaints of sensitive, pruritic, and irritated skin(3). • • • the skin microbiome a single square centimeter of the human skin can contain up to one billion microorganisms, including diverse communities of bacteria, fungi, mites, and virues(4). while bacteria account for ony 0.1% of this total (1 million organisms/cm2), they are generally considered to be the most important organisms in this ecosystem. bacteria are present on the skin surface, deeper layers of the epidermis, the dermis, and dermal adipose tissue(4). bacteria on the skin are from four main bacterial phylo(5): actinobacteria fimicutes proteobacteria bacteroidetes • • • water is crucial to microbial growth on the skin and the amount of water available to support this growth is referred to watre activity (a w ). water activity varies from 0 (totally dry) to 1.0 (pure water)(6). water activity strongly influences the growth of micro-organisms(7). staphylococcus aureus is able to grow until a w of 0.86, and pseudomonas fluorescens are not able to grow below an a w of 0.97. dry skin therefore favors growth of potentially invasive staphylococcus aureus and inhibits the growth of some commensal organisms. • • • role of skin microbiota in protection from infection and inflammation commensal species of micro-organisms that naturally reside on the surface of the skin are an integral part of the innate immune system. these bacteria contribute to protection against pathogen growth by competing for nutrients and space(2). some bacteria directly restrict the growth of competitors via production of antimicrobial compounds that can inhibit reproduction of closely related species without affecting the organisms producing them(2). • • infection bacteria from normal skin, such as s epidermis have been shown to suppress inflammation by inducing the secretion of interleukin-10, an anti-inflammatory cytokine, by antigen-presenting cells(8,9). s epidermis also secretes a unique lipoteichoic acid that inhibits both inflammatory cytokine release from keratinocytes and inflammation triggered by injury through a tlr2-dependent mechanism(9, 10). • • inflammation • there is a balanced interplay between the host cells and resident and/or transient bacterial populations that is continuously affected by intrinsic (host) and extrinsic (environmental) factors (figure 1). these factors alter the composition of the skin micro-organism community and may influence skin barrier function by inducing an unbalanced state of dysbiosis that may be evidenced in chronic inflammatory skin diseases, such as atopic dermatitis, psoriasis, rosacea, or acne(7, 11-13). factors involved in the relationship between skin microbiota and the skin barrier function are summarized in table 1. • • interplay between skin cells and bacteria in host defense and inflammation • several skin disorders (e.g., atopic dermatitis and psoriasis) are characterized by shifts in the skin microbiome(4, 14, 15). this shift has the potential to contribute to chronic inflammation. for example, s. aureus-associated molecular patterns bind to tlr2 to initiate long-lasting cutaneous inflammation driven by t helper cells(16). • • the importance of maintaining bacterial diversity moisturizers for maintenance of the skin barrier and a normal skin microbiome moisturizers bind water to the stratum corneum, improving the skin surface hydration. this has been shown repeatedly to improve the epidermal barrier function and reduce stinging, scaling, redness and cracks associated with xerosis(17). «to moisturize» does not only mean providing moisture, it also means preventing moisture evaporation from the skin. moisturizers can be formulated with emollient, humectant, moisturizing, or occlusive agents; and some formulations have potential prebiotic activity since they may provide food for the skin microbiota(18). moisturizers may also have anti-inflammatory properties that potentially impact the skin microbiota(19). • • actions of moisturizers • an important focus for the development of skin care products is maintaining an ecological balance in each skin niche(20). classical moisturizers are able to protect the skin, but new generation formulations have been specifically developed to manage inflammation and preserve or restore both the skin barrier and the skin microbiota diversity. key components of skin care products: • • formulation of skin care products • water activity and bacterial growth table 1. relationship between skin barrier and skin microbiota moisturizers can be formulated with deionized water or thermal water. in comparison to deionized water, thermal water can be viewed as containing prebiotic active ingredients (i.e., non-viable food components that confer health benefits associated with a modulation of the microbiota(18)). the presence of specific trace elements (e.g., selenium) in thermal water can drive the growth of beneficial bacterial species particularly if they are already found in its natural microbial content(21). the importance of thermal water is supported by results which showed that an emollient containing 50% la roche-posay thermal spring water (lrp-tsw) or the use of lrp-tsw alone during balneotherapy reduced disease severity and increased the diversity of skin microbiota in patients with either atopic dermatitis or psoriasis(21, 22). in both groups of patients, there was an increase in keratolytic bacteria of the xanthomonadaceae family that are naturally present at low levels on the skin and in lrp-tsw. • • water • prebiotics are ingredients and/or nutrients that selectively stimulate the growth and/or activity of commensal skin bacterial. prebiotics that might be included in skin products also have the potential to support maintenance of the normal skin microbiome(23). • prebiotics relationship between skin barrier and skin microbiota how skin microbiota interact with human skin barrier proteases may effect corneocytes desquamation and many skin proteins (ie, filaggrin) involved in stratum corneumcohesion lipases break down surface lipids with potentially irritant by-products including fatty acids ureases virulence factor found in various pathogenic bacteria; essential in host colonization and in maintenance of bacterial cells in tissues biofilm protect bacterial colonies on the skin bacteriocins bactericidal peptides regulating bacterial population quorum sensing needed for microbiota balance; effect not known on the skin skin nutrition supports commensal bacterial growth skin education immunology by lipopolysaccharides (gram-negative bacteria) and teichoic acids (gram-positive bacteria) how human skin barrier interacts with skin microbiota provides nutriments specific culture medium depending on microenvironment (moist, sebaceous, dry) control climate ph, temperature, uv light, moisture, and sweat controlled depending on skin area climate and nutriments counter-select bacteria growth bacterial balance regulation ß-defensis production emollient agents, such as ceramides, included in moisturizers may be good carbon and nitrogen sources for bacteria. ceramidase activity has been detected in bacterial skin flora and it has also been noted that skin ceramide levels are reduced in patients with atopic dermatitis(24). niacinamine (vitamin b 3 ) is combined with emollients in some skin products and it is also employed in culture media for some bacteria. it may have benefit in promoting skin health as it has been shown to inhibit the growth of methicillinresistant s aureus(25). • • other components conclusions understanding the complex relationship between normal skin barrier function and the skin microbiome is critical for the rational development of new skin care products. appropriately developed formulations have the potential to selectively increase the activity and growth of beneficial microbiota, prevent skin dysbiosis, and restore or maintain efficient skin barrier function. this is particularly important for conditions in which barrier dysfunction may occur, such as such as dry, sensitive and reactive skin; exposure to aggressive cosmetic or hygienic routines; after aesthetic procedures; or the use of therapeutics including antibiotics and corticosteroids. the studies reviewed suggest that inclusion of prebiotics and selenium-rich thermal spring water may all increase the efficacy of moisturizers and that some of this benefit may be due to positive effects on skin microbiota. • • • • references 1. salava a, lauema a. clin transl allergy 2014, 4: 4-33 2. sanford ja, gallo rl. semin immunol 2013, 25(5): 370-377 3. zeeuwen pl, kleerebezem m, timmerman hm, schalkwijk j. curr opin allergy clin immunol 2013, 13(5): 514-520 4. weyrich ls, dixit s, farrer ag, cooper aj. australas j dermatol 2015, 56(4): 268-274 5. grice ea, kong hh, conlan s et al. science 2009, 324(5931): 1190-1192 6. stevenson a, cray ja, williams jp, et al. isme j 2015, 9(6): 1333-1351 7. grice ea, serge ja. annu rev genomics hum genet 2012, 13: 151-170 8. chau ta, mccully ml, brintnell w, et al. nature medicine 2009, 15(6): 641-648 9. lai y, di nardo a, nakatsuji t, et al. nat med 2009, 15(12): 1377-1382 10. gallo rl, nakatsuji t. j invest dermatol 2011, 131(10): 1974-1980 11. schommer nn, gallo rl. trends microbiol 2013, 21(12): 660-668 12. grice ea. genome res 2015, 25(10): 1514-1520 13. rosenthal m, goldberg d, aiello a, larson e, foxman b. infect genet evol 2011, 11(5): 839-848 14. van rensburg jj, lin h, gao x, et al. m bio 2015, 6(5): e01315-15 15. grice ea. semin cutan med surg 2014, 33(2): 98-103 16. biedermann t, skabytska y, kaesler s, volz t. front immunol 2015, 6: 353 17. ring j, möhrenschlager m, weidinger s. chem immunol allergy 2012, 96: 24-29 18. fao technical meeting report on prebiotics: food quality and standards service (agns) food and agriculture organization of the united nations (fao); 2008 (http://www.aat-taa.eu/index/en/company/download/1262610500.html), last accessed: 17 january 2016 19. seite s, bieber t. clin cosmet investig dermatol 2015, 8: 479-483 20.lane me, hadgraft j, oliveira g, et al. int j cosmet sci 2012, 34(6): 496-501 21. martin r, henley jb, sarrazin p, seite s. j drugs dermatol 2015, 14(12): 1400-1405 22.flores ge, seite s, henley jb, et al. j drugs dermatol 2014, 13(11): 1365-1372 23. al-ghazzewi fh, tester rf. benef microbes 2014, 5(2): 99-107 24. ohnishi y, okino n, ito m, imayama s. clin diagn lab immunol 1999, 6(1): 101-104 25.kyme p, thoennissen, tseng cw, et al. j clin invest 2012 sep, 122(9): 3316-3329 • fc17posterlarochebaldwincutaneousmicrobiotaharmony.pdf skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 109 original research cost-benefit analysis of the pigmented lesion assay when introduced into the visual assessment / histopathology pathway for lesions clinically suspicious for melanoma daniel m. siegel, md, ms1, christopher murphy, jd2, kent d. wangsness, pharmd3, allyson g. perry, phd2, ian smith, fsa, maaa, fca3 1 suny downstate medical center, new york, ny 2 dermtech, inc., la jolla, ca 3 pharmacy advisory services, optum the current care pathway for evaluation of pigmented lesions is visual assessment, followed by surgical biopsy and histopathologic assessment (vah).1 however, the significant overlap in clinical and histopathologic features that exists between benign and malignant nevi make the classification of pigmented lesions a challenge for even highly experienced clinicians and pathologists.2, 3 the vah pathway relies on image and pattern recognition/interpretation, which is subjective in nature.1, 3, 4 this, paired with concern regarding potential consequences of missing a melanoma, has resulted in a vah pathway with a relatively low sensitivity (65% for up to stage pt1a – 84% for all abstract objective: to evaluate the potential savings to health plans when the pigmented lesion assay (pla) is incorporated into the assessment of pigmented lesions clinically suspicious for melanoma. methods: a return on investment (roi) model was developed from a us payor perspective to determine the per member per month (pmpm) net savings impact of incorporating pla into the visual assessment/histopathology (vah) pathway. using 2019 claims data for patients with lesions suspicious for melanoma (n=239,854), use of pla in year 1 was modeled and followed through subsequent years. costs were assessed through the pathway of initial visual assessment, surgical procedure(s), histopathology, and subsequent management. results: the roi model predicted annual net savings of $0.54 pmpm for commercial health plans over a three-year period with incorporation of pla into the vah pathway. in this analysis, 95.7% of surgically assessed lesions clinically suspicious for melanoma were diagnosed as benign, with 30.4% of patients with benign lesions undergoing a more advanced procedure (e.g., excision), either initially or following a biopsy. melanoma diagnosis rates associated with biopsy only, excision only, and biopsy followed by excision procedures in the vah pathway were 0.9%, 0.1%, and 17.9%, respectively. conclusion: incorporation of the pla into the vah pathway for assessing suspicious pigmented lesions results in savings for commercial health insurance plans. use of the pla improves patient care by using genomic assessments to minimize avoidable surgical procedures on benign lesions, enrich the population of melanomas diagnosed, and decrease downstream costs of late-stage melanoma diagnoses. introduction skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 110 melanomas) and a negative predictive value (npv) of 83%.3, 5-7 these findings demonstrate the need for objective, costeffective technologies to help improve the assessment, classification, and management of pigmented lesions. the pla is a noninvasive test that objectively measures genomic markers associated with melanoma within skin tissue samples collected via adhesive patches.8-10 the pla is used to identify high-risk lesions (severely dysplastic nevi as well as in situ and invasive melanomas)6, 11-13 and guide management to either a) biopsy and histopathologic evaluation or b) clinical surveillance.6, 14, 15 use of the pla is supported by the national comprehensive cancer network (nccn) guidelines, which state that pre-diagnostic noninvasive patch testing may be helpful to guide biopsy decisions (category 2a recommendation).16 the pla has a 91% sensitivity for melanoma and an npv of over 99%; a lesion clinically suspicious for melanoma that tests negative by pla has a less than 1% probability of being diagnosed histopathologically as a melanoma.8, 17 previous studies have demonstrated that utilization of the pla increases accuracy of pigmented lesion classification as either benign or malignant and thus dramatically reduces surgical procedures currently used to rule out melanoma.14 the current study aims to build on the clinical value of the pla by investigating the economic value of the pla in the assessment of suspicious pigmented lesions. return-on-investment (roi) modeling is a method used by actuaries to prioritize risks and determine the most cost-effective option for managing those risks. roi models developed for healthcare payors estimate the potential incremental financial “investment” (costs) relative to the “return” (cost-offsets/savings) for specific cohorts of health plan members. roi models incorporate net-cost, member churn, and medical-cost offset scenarios, leveraging proxy client data from claims databases with sensitivity testing of various population and assumption scenarios. in this study, an roi model was developed to evaluate potential savings for commercial health insurance plans when the pla is introduced into the vah pathway to guide management of pigmented skin lesions clinically suspicious for melanoma. the roi model was developed from a health plan perspective and designed to assess the per member per month (pmpm) net cost/savings impact of incorporating pla into the vah pathway. the model was built from claims data, financial factor inputs, costs associated with the vah pathway, pla investment costs, assumptions related to lesion progression in non-detected melanomas, and the number of target members for pla in a plan. the inputs are modifiable, allowing the user to customize the pmpm net cost/savings impact calculation to their plan’s data and extrapolate aggregate year-over-year cost/savings to the plan. claims data and member cohorts data were sourced from proprietary databases that contain claims data for approximately 13.8 million commercially insured members across the united states who had a plan covering both medical and pharmacy benefits between january 1, 2019 and december 31, 2019.18 a subset of these data relevant to skin lesions clinically suspicious for melanoma (n=239,854) was used to develop the roi model. to account methods skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 111 table 1. member cohorts cohort definition 1 suspicious lesion • d48.5/d49.2 diagnosis code but no further treatment related to the suspected lesion • excludes nonmelanoma codes including, but not limited to, c44.xx, d04.xx, d23.xx, and l codes (except 'l98.9', 'l98.8') 2 a benign lesion with 1 surgical procedure • benign diagnosis (d22) with biopsy/pathology procedures • benign diagnosis (d22) or suspicious lesion (d48.5, d49.2) + advanced procedure (i.e., excisions, sentinel node biopsies, mohs surgery) 2 b benign lesion with 2 or more surgical procedures • benign diagnosis (d22) with biopsy/pathology procedures + excision procedures • suspicious lesion (d48.5, d49.2) with biopsy/pathology procedures + excision procedures 3 non-advanced melanoma (managed by biopsy/excision) • melanoma diagnosis (c43/d03) with biopsy/pathology procedures • melanoma diagnosis + excision procedures 4 advanced melanoma (metastatic and/or managed with advanced treatment) • melanoma diagnosis (c43/d03) + metastatic diagnosis (c79.2) • melanoma diagnosis (c43/d03) with advanced cancer treatments each member was allocated to the cohort hierarchically. (cohort 4 → 1) for different levels of costs associated with suspicious skin lesions of various diagnoses/management and estimate cost to the plan, four cohorts of skin lesions clinically suspicious for melanoma were classified based on diagnosis codes and/or procedure codes (table 1 and appendices 1-3). cost estimation methodology the health plan cost for diagnosis and management of melanoma through the vah pathway was determined and then compared to a pathway incorporating pla to help guide patient management decisions. using trended 2019 claims data, a population using pla in year 1 was modeled and followed through subsequent years.18 assessments were made through the pathway of initial diagnosis of lesions suspicious for melanoma and procedures for biopsy, pathology, and subsequent treatments. several differences were noted and modeled: 1) the use of the pla compared to standard biopsy/pathology; 2) the shift in cost to the plan when providers use the pla to guide patient management decisions based on the genomic results of the pla instead of performing surgical procedures on pathologically benign lesions; 3) the shift in cost from genomic assessment and treatment of future melanoma, through objective criteria, compared to late-stage cancer treatment in future years. future costs1 to the plan were estimated by using the historic costs for these pathways and trending them forward by historical medical cost trend (4%). member churn rate (15%), the percentage of members in a plan who will leave the plan each year, and plan cost share percentage (84%) were applied to the model to determine the true cost to the plan.19 from this, the model aggregated 1 only directly related costs are considered. see appendix 3 for the definition of ‘direct’ costs. skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 112 future years and discounted the cost by prevailing interest rates estimated from the 10-year u.s. treasury t-bill rate (1%) to arrive at the cost in terms of dollars today.20 inputs for cost trend, churn rate, and cost share were based on claims dated between january 1, 2017 and december 31, 2019.19 estimating return-on-investment figure 1 includes visual representations of the roi model calculations, including final savings, genomic assessment savings, procedure avoidance savings, pla costs, and plan net cost per member per month. each variable is further described below. genomic assessment savings is a measurement of the cost savings realized due to genomic assessment of pigmented lesions suspicious for melanoma through incorporation of the pla into the vah pathway. the pla identifies lesions at high risk for melanoma based on the presence of genomic markers associated with melanoma.8, 11, 13 with histopathology, cellular atypia is detectable, but pla detects genomic atypia, which cannot be ascertained visually.11, 13 the additional nonadvanced melanoma (managed by biopsy/excision) and advanced melanoma (metastatic and/or managed with advanced treatment) cases included in the calculation are assumed to be melanomas that would not otherwise be detected by the vah pathway during a particular office visit and were derived using biostatistics from sensitivity analyses comparing vah and pla pathways.3, 8, 21 the nonadvanced/advanced melanoma costs per patient represent the costs that would be incurred by the plan based on the likelihood that the melanomas missed by the vah figure 1. roi model calculations i excludes melanomas detected via vah pathway alone. non-advanced melanoma: managed by biopsy/excision advanced melanoma: metastatic and/or managed with advanced treatment skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 113 pathway during an office visit would be identified during the subsequent visit and how quickly the melanomas missed on the initial visit were likely to progress (table 2).22, 23 financial factor inputs of cost trend, cost share, and interest rate were also used to calculate nonmelanoma/melanoma costs (table 2).19 procedure avoidance savings is a measurement of the cost savings realized due to not performing biopsies or follow-up treatments on non-malignant lesions as determined by the pla. the number of patients with benign lesions that underwent biopsy with or without follow-up procedures and associated costs were based on 2019 claims data. a benign lesion follow-up procedure rate of 14.9% was used based on the claims data (table 2).18 pla costs is a measurement of investment required for incorporating the pla into the vah pathway. the number of patients with lesions that underwent biopsy was based on 2019 claims data. pla allowed cost inputs include the cms allowable cost per pla ($760)24 as well as the average cost of an office visit to evaluate a suspected pigmented lesion ($190) and the average plan cost share (84%) based on 2019 claims data (table 2).18 figure 1b shows the calculation for plan net pmpm cost savings, calculated as the aggregate final savings divided by the total health plan member months. final savings was calculated as genomic assessment savings + procedure avoidance savings – pla costs (figure 1a). total health plan member months is a direct measurement from experience data, which was derived from the 2019 claims data for the current study (table 2).18 the demographics of the study population used for the roi analysis and for the larger national claims database are summarized in table 3. the study population subset included health plan members with a lesion clinically suspicious for melanoma (n=239,854). claims associated with other dermatologic conditions (basal cell carcinoma, squamous cell carcinoma, actinic keratoses, warts, etc; see table 1) were excluded from this analysis. the study population was 57.7% female; 95.7% of members were ≥18 years old. the proportion of lesions in cohorts 1, 2a, 2b, 3, and 4 were 16.5%, 68.0%, 11.9%, 3.1%, and 0.5%, respectively (table 4). return-on-investment with pla the roi model predicted the annual net cost/savings for commercial plans incorporating pla into the vah pathway. when using default values (table 2), the roi model predicted an annual net savings of $0.54 pmpm over a three-year period (aggregate savings of $5.66 million for a plan of 1 million members). net savings were driven primarily by the increased sensitivity of genomic assessment compared to visual assessment (genomic assessment savings). scenario and threshold testing was done to determine the sensitivity of the net pmpm savings at three years to various assumptions used within the genomic assessment savings calculations of the roi model (table 2). the default value for additional melanomas identified by pla was 26%, which was driven by sensitivity analyses comparing vah and pla pathways3, 8, 21; results skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 114 table 2. variables and default values variable name variable description and assumptions default values cost trend the annual trend applied to medical and pharmacy costs year-on-year changes19,20 commercial: 4% interest rate interest rate used for discounting, based on the 10-year u.s. treasury t-bill rate20 1% churn rate the percentage of members in a plan who will leave the plan each year19,20 15% cost share the percentage of plan’s cost share19,20 commercial: 84% pla cost average allowed cost of pla treatment24 $760 suspicious lesion office visit cost cost of an office visit, based on the percentage of plan’s cost share, to assess a lesion suspicious for melanoma.18,20 commercial: $190 benign lesion with no follow-up procedure cost direct cost (medical + rx) for benign lesion biopsy without follow-up procedure (subset of cohort 2a)18 represents total cost of receiving a biopsy. commercial: $372 benign lesion with advanced procedure only with no followup procedure cost direct cost (medical + rx) for advanced procedure on a benign lesion, without follow-up procedures (subset of cohort 2a)18 represents total cost of receiving an advanced procedure instead of a biopsy. commercial: $746 benign lesion with follow-up procedure cost direct cost (medical + rx) for suspicious/benign lesion biopsy with follow-up procedure(s) (cohort 2b)18 represents total cost of receiving a biopsy and follow-up procedures. commercial: $1,118 benign lesion follow-up procedure rate the number of patients with benign lesions that underwent biopsy with follow-up procedures (cohort 2b) divided by the number of patients with benign lesions that underwent biopsy with or without follow-up procedures (subset of cohort 2a + cohort 2b)18 commercial: 14.9% advanced procedure without biopsy rate the percentage of cases in which the physician performed a more advanced surgical procedure without an initial biopsy (subset of cohort 2a).18 commercial: 15.5% additional melanomas caught by pla the percentage of additional melanoma patients identified through use of pla among patients in “melanoma with biopsy/excision” (cohort 3) or “advanced melanoma” (cohort 4)3,20,21 multiplied by market share for pla 26% progression to melanoma the percentage of patients who progress to melanoma from additional patients identified by pla with no prior procedures/treatments (75%): 33% of lesions will be classified as nonadvanced melanoma (cohort 3) and 67% will be classified as advanced melanoma (cohort 4)20,22,23 progression % = 75% split cohort 3 and 4 = 33% for cohort 3 and 67% for cohort 4 total health plan member months the sum of the number of months of coverage the population has over a full year18 145,134,689 market share for pla the percentage of patients who will receive pla 100% skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 115 a 10% decrease in this rate (23.4%) resulted in $0.43 pmpm net savings (20% decrease), and a 10% increase in this rate (28.6%) resulted in $0.65 pmpm net savings (20% increase). the default value for progression to melanoma was 75%; a 10% decrease in this rate (67.5%) results in $0.48 pmpm net savings (9% decrease), and a 10% increase in this rate (82.5%) results in $0.59 pmpm net savings (9% increase). the default values for distribution in patients’ progression to melanoma was 33%:67% for non-advanced to advanced melanoma; a 10% decrease in this rate for non-advanced melanoma (30%:70%) resulted in $0.58 pmpm net savings (9% increase), and a 10% increase in this rate for nonadvanced melanoma (36%:64%) results in $0.50 pmpm net savings (8% decrease). patient outcomes surgical procedures and diagnostic outcomes were assessed in the study population. of patients who received a diagnosis of “neoplasm of uncertain behavior of skin” (d48.5) or “neoplasm of unspecified behavior of bone, soft tissue, and skin” (d49.2), 83.5% received at least one surgical procedure to rule out melanoma (table 4, cohorts 2-4). of these surgically assessed lesions, 4.3% were diagnosed as melanoma (number needed to biopsy: 23), and 95.7% were diagnosed as benign. in 15.5% of benign cases, the patient underwent a more advanced procedure (e.g., excision) instead of a biopsy for diagnosis. another 14.9% of patients received additional advanced table 3. national claims database and study population demographics (2019 data) national claims database commercially insured members with a plan covering both medical and pharmacy benefits study population subset subjects with lesions clinically suspicious for melanoma countsi (n=13,822,351) proportion of total count countsi (n=239,854) proportion of total count region northeastii 2,250,823 16.3% 28,546 11.9% midwestiii 3,348,458 24.2% 53,907 22.5% southiv 5,505,252 39.8% 108,128 45.1% westv 2,717,818 19.7% 49,273 20.5% gender male 6,997,655 50.6% 101,353 42.3% female 6,824,696 49.4% 138,501 57.7% age band 0-17 2,919,987 21.1% 10,241 4.3% 18-44 6,348,274 45.9% 94,743 39.5% 45-64 4,032,421 29.2% 116,808 48.7% 65-74 426,794 3.1% 14,451 6.0% 75-84 67,415 0.5% 2,685 1.1% 85+ 27,461 0.2% 926 0.4% i unique members ii northeast ct, me, ma, nh, ri, vt, nj, ny, pa iii midwest il, in, mi, oh, wi, ia, ks, mn, mo, ne, nd, sd iv south de, dc, fl, ga, md, nc, sc, va, wv, al, ky, ms, tn, ar, la, ok, tx v west az, co, id, mt, nv, nm, ut, wy, ak, ca, hi, or, wa skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 116 table 4. cohort distribution of study population cohort countsi proportion of total count 1 suspicious lesion 39,624 16.5% 2a benign lesion with 1 surgical procedure 163,006 68.0% 2b benign lesion with 2 or more surgical procedures 28,577 11.9% 3 non-advanced melanoma (managed by biopsy/excision) 7,521 3.1% 4 advanced melanoma (metastatic and/or managed with advanced treatment) 1,126 0.5% i unique members surgical procedure(s) following a benign diagnosis, demonstrating a total advanced procedure rate of 30.4% for benign lesions. since the pla is intended to be used for clinically suspicious pigmented lesions that are not overtly benign or malignant,8 data from cohorts 2 and 3 of the study population (table 1) were used to determine the potential impact in both cost and quality of care that the pla may provide. each of these cohorts used one of three procedure categories to reach a diagnosis of benign (cohort 2) or non-advanced melanoma (cohort 3): a) biopsy only (n= 135,473); b) excision only (n= 28,086); and c) biopsy followed by excision (n= 34,818). diagnosis rates of each procedural category are summarized in table 5. in category a, when a biopsy was the only procedure performed, 99.1% of patients received a diagnosis of benign (i.e., d22.xx), and 0.9% of patients received a diagnosis of nonadvanced melanoma (i.e., c43.xx, d03.xx). in category b, when an excision was the only procedure performed, 99.9% of patients received a diagnosis of benign, and 0.1% of patients received a diagnosis of nonadvanced melanoma (i.e., c43.xx, d03.xx). in category c, when a biopsy was performed followed by an excision, 82.1% of patients received a diagnosis of benign (i.e., d22), and 17.9% of patients received a diagnosis of nonadvanced melanoma (i.e., c43.xx, d03.xx). categories b and c represent situations when the treating clinician decides to excise the lesion. when combining instances where a lesion is excised, 90.0% of patients receive a diagnosis of benign (i.e., d22), and 10.0% of patients receive a diagnosis of nonadvanced melanoma (i.e., c43.xx, d03.xx). table 5: surgical procedure rates for benign lesions (cohort 2) and non-advanced melanomas (cohort 3) procedure category countsi benign diagnosisii non-advanced melanoma diagnosisiii a biopsy only 135,473 99.1% 0.9% b excision only 28,086 99.9% 0.1% c biopsy followed by excision 34,818 82.1% 17.9% b+c any excision 62,904 90.0% 10.0% data are derived from 2019 claims data pulled in december 2021. i unique members ii d22.xx iii c43.xx, d03.xx skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 117 the pla is a noninvasive genomic test used to guide patient management decisions for skin lesions clinically suspicious for melanoma; lesions that test positive are recommended for biopsy and histopathology, and those that test negative are recommended for clinical surveillance.6, 8, 14, 15 a previous health economic analysis showed that routine use of pla reduces cost compared to the vah pathway in medicare patients with suspicious pigmented lesions.5 in agreement with these findings, the roi model in this study indicates that incorporating the pla into the vah pathway can provide cost savings to commercial health insurance plans. this study also indicates where the pla can improve outcomes of patients with lesions suspicious for melanoma. the roi model showed that adoption of pla may result in savings of $0.54 pmpm over a three-year period. these cost savings were realized due to the use of genomic assessments to guide biopsy decisions for pigmented lesions clinically suspicious for melanoma. the performance metrics of the pla (91% sensitivity, 99% npv) improve upon those of the vah pathway (65%-84% sensitivity, 83% npv),3, 5-8 resulting in more accurate classification of pigmented lesions based on genomics. genomic aberrations precede visual changes in melanoma;25 thus genomic assessments with the pla are able to identify high-risk lesions for melanoma that may not otherwise be evaluated by the vah pathway.6, 11, 13 using the pla’s genomic assessments to guide biopsy decisions could reduce overall treatment costs associated with vah while improving patient outcomes. in addition to cost savings, our study uncovered opportunities to improve upon the quality of care offered via the vah pathway. traditionally, clinicians have had to rely on image and pattern recognition to classify pigmented lesions as benign or malignant, which is a subjective and challenging exercise.1-4 with the goal of never missing a melanoma, clinicians have exercised an abundance of caution when assessing pigmented lesions. for example, 83.5% of clinically suspicious pigmented lesions were surgically biopsied in this study, with 95.7% of those diagnosed as benign. furthermore, the three procedural assessment pathways employed (biopsy only, excision only, and biopsy followed by excision) all yielded low rates of melanoma diagnoses (0.9%, 0.1%, and 17.9%). though the approaches and outcomes above are understandable given the tools historically available, these data demonstrate the need for additional, reliable information that can more accurately classify pigmented lesions for enhanced decision making and improved outcomes. nccn guidelines indicate that prediagnostic noninvasive patch testing may be helpful to guide biopsy decisions.16 the pla aligns with this guidance by noninvasively providing objective genomic information that indicates if a suspicious pigmented lesion is at high risk for melanoma.8, 10, 11, 13 improved outcomes for patients occur when they receive appropriate care for their condition, receive more effective care, and/or avoid unnecessary procedures/therapy or testing.26 with the pla, approximately 15% of lesions test positive and are recommended for biopsy and histopathologic evaluation, and the remaining 85% test negative and are recommended for clinical surveillance, thus avoiding a surgical procedure.27 a separate analysis of pla claims from 2020 independently validated these outcomes: discussion skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 118 ~20% of claims received a surgical procedure (i.e., presumed positive pla result) and ~80% of claims did not receive a surgical procedure (i.e., presumed negative pla result).28 a recent long-term follow-up study demonstrated that clinical surveillance of pla-negative lesions is appropriate; in this study, <1% of 1,535 pla-negative lesions exhibited clinical changes leading to melanoma diagnoses (in situ or pt1a) during 24-36 months of follow-up.17 taken together, these data show that the pla can improve patient outcomes by 1) identifying the small subset of clinically suspicious lesions at high risk for melanoma, and 2) avoiding surgical procedures of benign lesions. incorporation of the pla into the vah pathway enhances decision making for lesions clinically suspicious for melanoma, improves the quality of patient care, and drives lower overall costs to commercial health insurance plans. acknowledgements: the authors thank dr. michael walker (stanford university and walker biosciences) for help with statistical analyses. conflict of interest disclosures: dr. dms is an investigator and advisor to dermtech, cm and agp are employees of dermtech, inc. funding: this study was supported by dermtech, inc. corresponding author: christopher murphy, jd dermtech, inc. email: cmurphy@dermtech.com references: 1. swetter sm, tsao h, bichakjian ck, et al. guidelines of care for the management of primary cutaneous melanoma. j am acad dermatol. jan 2019;80(1):208-250. doi:10.1016/j.jaad.2018.08.055 2. babino g, lallas a, agozzino m, et al. melanoma diagnosed on digital dermoscopy monitoring: a side-by-side image comparison is needed to improve early detection. j am acad dermatol. sep 2021;85(3):619-625. doi:10.1016/j.jaad.2020.07.013 3. elmore jg, barnhill rl, elder de, et al. pathologists' diagnosis of invasive melanoma and melanocytic proliferations: observer accuracy and reproducibility study. bmj. jun 28 2017;357:j2813. doi:10.1136/bmj.j2813 4. urso c, rongioletti f, innocenzi d, et al. histological features used in the diagnosis of melanoma are frequently found in benign melanocytic naevi. j clin pathol. apr 2005;58(4):409-12. doi:10.1136/jcp.2004.020933 5. hornberger j, siegel dm. economic analysis of a noninvasive molecular pathologic assay for pigmented skin lesions. jama dermatol. sep 1 2018;154(9):1025-1031. doi:10.1001/jamadermatol.2018.1764 6. ferris lk, gerami p, skelsey mk, et al. realworld performance and utility of a noninvasive gene expression assay to evaluate melanoma risk in pigmented lesions. melanoma res. oct 2018;28(5):478-482. doi:10.1097/cmr.0000000000000478 7. malvehy j, hauschild a, curiel-lewandrowski c, et al. clinical performance of the nevisense system in cutaneous melanoma detection: an international, multicentre, prospective and blinded clinical trial on efficacy and safety. br j dermatol. nov 2014;171(5):1099-107. doi:10.1111/bjd.13121 8. gerami p, yao z, polsky d, et al. development and validation of a noninvasive 2-gene molecular assay for cutaneous melanoma. j am acad dermatol. jan 2017;76(1):114-120 e2. doi:10.1016/j.jaad.2016.07.038 9. yao z, allen t, oakley m, samons c, garrison d, jansen b. analytical characteristics of a noninvasive gene expression assay for pigmented skin lesions. assay drug dev technol. aug 2016;14(6):355-63. doi:10.1089/adt.2016.724 10. yao z, moy r, allen t, jansen b. an adhesive patch-based skin biopsy device for molecular diagnostics and skin microbiome studies. j drugs dermatol. oct 1 2017;16(10):979-986. 11. brouha b, ferris l, skelsey m, et al. genomic atypia to enrich melanoma positivity in biopsied lesions: gene expression and pathology findings from a large u.s. registry study. skin conclusion mailto:cyberderm@dermsurg.org skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 119 the journal of cutaneous medicine. 2021;5(1):13-18. 12. lott jp, elmore jg, zhao ga, et al. evaluation of the melanocytic pathology assessment tool and hierarchy for diagnosis (mpath-dx) classification scheme for diagnosis of cutaneous melanocytic neoplasms: results from the international melanoma pathology study group. j am acad dermatol. aug 2016;75(2):356-63. doi:10.1016/j.jaad.2016.04.052 13. jackson sr, jansen b, yao z, ferris lk. risk stratification of severely dysplastic nevi by noninvasively obtained gene expression and mutation analyses. skin the journal of cutaneous medicine. 2020;4(2):105-110. 14. ferris lk, jansen b, ho j, et al. utility of a noninvasive 2-gene molecular assay for cutaneous melanoma and effect on the decision to biopsy. jama dermatol. jul 1 2017;153(7):675-680. doi:10.1001/jamadermatol.2017.0473 15. brouha b, ferris l, skelsey m, et al. real-world utility of a non-invasive gene expression test to rule out primary cutaneous melanoma: a large us registry study. journal of drugs in dermatology. 2020;19(3):257-262. doi:10.36849/jdd.2020.4766 16. national comprehensive cancer network (nccn). nccn clinical practice guidelines in oncology (nccn guidelines®). melanoma: cutaneous. version 1.2022. national comprehensive cancer network. updated december 3, 2021. 17. skelsey m, brouha b, rock j, et al. non-invasive detection of genomic atypia increases realworld npv and ppv of the melanoma diagnostic pathway and reduces biopsy burden. skin the journal of cutaneous medicine. 2021;5(5):512523. 18. optum, inc. commercial claims data, january 1, 2019 to december 31, 2019. 19. optum, inc. commercial claims data, january 1, 2017 to december 31, 2019. 20. professional experience and judgment of the inter-disciplinary modeling team and/or experts. 21. us preventive services task force. screening for skin cancer: us preventive services task force recommendation statement. jama. 2016;316(4):429-435. doi:10.1001/jama.2016.8465 22. liu w, dowling jp, murray wk, et al. rate of growth in melanomas: characteristics and associations of rapidly growing melanomas. arch dermatol. dec 2006;142(12):1551-8. doi:10.1001/archderm.142.12.1551 23. tejera-vaquerizo a, nagore e, melendez jj, et al. chronology of metastasis in cutaneous melanoma: growth rate model. j invest dermatol. apr 2012;132(4):1215-21. doi:10.1038/jid.2011.433 24. centers for medicare & medicaid services. clinical laboratory fee schedule files. https://www.cms.gov/medicare/medicare-fee-forservice-payment/clinicallabfeesched/clinicallaboratory-fee-schedule-files. accessed december 16, 2021. 25. puglisi r, bellenghi m, pontecorvi g, pallante g, care a, mattia g. biomarkers for diagnosis, prognosis and response to immunotherapy in melanoma. cancers (basel). jun 9 2021;13(12)doi:10.3390/cancers13122875 26. blue cross blue shield association policy 2.04.146. 27. data on file. dermtech, inc. la jolla, california. 28. optum, inc. commercial claims data, january 1, 2020 to december 31, 2020. skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 120 appendix appendix 1. advanced cancer treatment codes chemotherapy (advanced cancer) ndc codes ’00078068266’, ‘00173084608’, ‘00078068166’, ‘00173084708’, ‘00078066615’, ‘00173084913’, ‘00078066815’, ‘00173084813’, ‘50242009001’, ‘50242009002’, ‘50242071701’, ‘70255002001’, ‘70255002002’, ‘70255002501’, ‘70255002502’, ‘70255002503’, ‘70255002504’, ‘70255001002’ advanced cancer procedure codes ‘77401’, ‘77402’, ‘77407’, ‘77412’, ‘g6003’, ‘g6004’, ‘g6005’, ‘g6006’, ‘g6007’, ‘g6008’, ‘g6009’, ‘g6010’, ‘g6011’, ‘g6012’, ‘g6013’, ‘g6014’, ‘77385’, ‘77386’, ‘g6015’, ‘g6016’, ‘77417’, ‘77387’, ‘g6001’, ‘g6002’, ‘g6017’, ‘77014’, ‘77520’, ‘77521’, ‘77522’, ‘77523’, ‘77524’, ‘77525’, ‘77422’, ‘77423’, ‘77371’, ‘77372’, ‘77373’, ‘77600’, ‘77601’, ‘77602’, ‘77603’, ‘77604’, ‘77605’, ‘77606’, ‘77607’, ‘77608’, ‘77609’, ‘’77610’, ‘77611’, ‘77612’, ‘77613’, ‘77614’, ‘77615’, ‘77616’, ‘77617’, ‘77618’, ‘77619’, ‘77620’, ‘77778’, ‘77770’, ‘77771’, ‘77772’, ‘0394t’, ‘0395t’, ‘77424’, ‘77425’, ‘77789’, ‘77750’, ‘77761’, ‘77763’, ‘77790’, ‘77295’, ‘77300’, ‘77331’, ‘77301’, ‘77338’, ‘77306’, ‘77307’, ‘77316’, ‘77317’, ‘77318’, ‘77321’, ‘77332’, ‘77333’, ‘77334’, ‘77336’, ‘77370’, ‘j9271’, ‘j9299’, ‘j9228’, ’j9325’, ‘j9130’, ‘j9022’ appendix 2. procedure codes used to define cohorts for biopsy, pathology, excision, and destruction skin biopsy ‘11100’, ‘11101’, ‘11102’, ‘11103’, ‘11104’, ‘11105’, ‘11106’, ‘11107’, ‘11300’, ‘11301’, ‘11302’, ‘11303’, ‘11305’, ‘11306’, '11307', '11308', '11310', '11311', '11312', '11313', '67810', '69100', '69105' pathology '88300', '88301', '88302', '88303', '88304', '88305', '88306', '88307', '88308', '88309', '88312', '88313' excision exclusions: excision claims that come with exclusion diagnosis codes (c44, d04, d23 or l codes except l98.9 or l98.8) as primary are not included. '17311', '17312', '17313', '17314', '17315', '21936', '22902', '22903', '23071', '23075', '24071', '24075', '25071', '25075', '26111', '26115', '27043', '27047', '27327', '27337', '27618', '27632', '28039', '28043', '69110', '69120', '69145', '69150', '69155', '38500', '38505', '38510', '38515', '38520', '38525', '38530', '11400-11446', '11600-11646' destruction '17000', '17003', '17110', '17004', '17262', '17111', '17261', '17281', '17260', '17271', '17272', '17263', '17282', '17280', '17270' ,'17273', '17264', '17283', '17106', '17266', '17274', '17284' skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 121 appendix 3. direct cost (primary condition cost) direct cost was estimated as follows: ▪ for biopsy claims: claims with diagnosis codes c43, d03, d22, d48.5 or d49.2 ▪ for other claims: ▪ benign or melanoma members’ claims which come with destruct procedures2 on the same day ▪ claims with diagnosis codes c43, d03, d22, d48.5 or d49.2 [note: an exclusion code (c44, d04, d23 or l codes except l98.9, l98.8) doesn’t come as primary] ▪ claims with procedures codes in excision/advanced cancer procedures/advanced melanoma ndcs3 ▪ claims of advanced melanoma patients with advanced melanoma procedures, diagnosis code c79.2 or cancer drgs (595, 596) or advanced melanoma ndcs 2 see appendix 2. 3 see appendix 1. skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 250 brief article polypoid melanoma: diagnostic hardships concerning a rare melanoma variant aleia boccardi1, oms iv, joanna trigg, do2, paloma reiter, do2, dimitria papadopoulos, do2, suzanne sirota rozenberg, do2 1 touro university california college of osteopathic medicine, vallejo, ca 2 st. john’s episcopal hospital, department of dermatology, far rockaway, ny polypoid melanoma is a rare variant of melanoma that most frequently appears as an ulcerated, exophytic nodule that can be amelanotic and occur in a younger patient demographic. the initial lesion exhibits a slow radial growth phase but within months can transform into a rapidly growing vertical phase.1 pm can fit into two subcategories, both of which individually predict higher mortality rates. nodular melanoma is considered the most aggressive, with five and ten year survival at 51.67% and 38.75%, respectively.2 amelanotic melanomas can arise within any histological subtype, and account for 2-20% of all melanomas.3 defining a lesion as amelanotic or not is based off either a visual inspection of the lesion before biopsy or lack of melanin pigment seen on hematoxylineosin stained sections.3 the lack of pigment has also been associated with increased rapid growth, increased breslow thickness, and mitoses.4 these traits can lead to late biopsy and poorer prognosis. below we present a case highlighting the diagnostic hardships that accompany the presentation of pm. a 46 year old caucasian female with a history of hypertension, asthma, and abstract skin cancer is the most common cancer in the united states, with a disproportionate amount of cases diagnosed as basal and squamous cell carcinoma. while melanoma accounts for only a small fraction of all skin cancers, it has greater potential for invasion and metastasis if not identified and treated early. within this higher mortality subtype of skin cancer, there is a rare variant called polypoid melanoma (pm) that compounds the diagnostic hardships of distinguishing melanomas from more benign lesions. this aggressive melanoma has a wide variety of clinical presentations that can range from an amelanotic, sessile papule to a pedunculated, melanotic nodule. its growth pattern also contributes to the lesion’s ambiguity, generally undergoing a slow development period that can spontaneously transition into rapid growth. this can present challenges for all potential parties involved, including the patient, primary physicians, and dermatologists alike. such characteristics can act as barriers in clinically determining the urgency of a biopsy, thereby affecting time to diagnosis and prognosis of their patients. we report one such case of protracted diagnosis of polypoid amelanotic melanoma due to a combination of aesthetic ambiguity and lack of patient proactivity. introduction case report skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 251 hyperlipidemia presented with a growth on the right lateral thigh for the past 5 years. patient stated that it had been growing slowly over time but recently noted a rapid change in size. it also became itchy, darkened and crusted at the tip of the lesion, but denied bleeding or pain. on physical exam, the right lateral thigh showed a 3 cm largely flesh colored exophytic and pedunculated plaque with a crusted necrotic tip, extending down to half the plaque (figure 1). figure 1. polypoid melanoma. clinical picture of an exophytic pedunculated flesh colored plaque with necrosis and ulceration at the tip extending to middle of lesion. there was no surrounding pigment noted at the base. a shave removal of the lesion was performed. the histologic report stated the melanoma was at least 5.0mm in thickness and extended to the base (figure 2a-b). there were atypical melanocytes in both the epidermis and dermis. ulceration was present and 6 mitoses/mm2 were noted. microsatellitosis, tumor regression, and lymphovascular invasion were all absent. these relevant findings lead to a pathologic primary tumor staging of pt4b of a polypoid melanoma. the patient was immediately referred to a surgical oncologist for further management. while uncommon melanoma variants account for less than 5% of melanomas, their route to treatment can be prolonged by misdiagnoses.5 specifically for the polypoid variant, the superficial appearance of the tumor is usually described as a pedunculated or sessile lesion that can be ulcerated with or without pigmentation. such morphologic diversity leaves the physician’s differential unfocused and open for error. if melanotic, one could think of infarcted intradermal nevi, nodular basal cell carcinoma, or merkel cell carcinoma. if amelanotic, the lesion might look similar to an acrochordon, pyogenic granuloma, or vascular malformation. when ulcerated, possibilities of keratoacanthoma dermatofibrosarcoma protuberans enter the mix. with this broad range of possibilities including benign entities, the urgency of further analysis can be masked. however, only histological evaluation of the lesions can provide clearer delineations. pm would show high mitotic count with cellular atypia and nuclear pleomorphism. while the poor prognosis of this disease was found to be related to the tumor’s unusual thickness and extent of ulceration, it can be compounded by late diagnosis. both contributing to polypoid melanoma’s low five-year survival rate—42%.6 this is contrasted with a 57% 5-year survival for non-polypoid nodular melanoma, and a 77% for superficial spreading melanoma.6 melanoma is almost universally correlated with “discolored moles” by the general discussion skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 252 figure 2 a) h&e 4x. collection of melanocytes in a both epidermis and dermis with ulceration. b) h&e 40x. grouping of atypical melanocytes with scattered mitoses present population. when abnormal, non-pigmented lesions arise, they may be unnoticed longer and incite less anxiety in the bearer than their pigmented counterpart. such traits could contribute to procrastination in seeing a doctor, let alone a dermatologist. once at the office, the abcde (asymmetry, border irregularity, color, diameter, and evolution) acronym used to identify suspicious skin lesions for melanoma is affected due to the absence of color. with one of the five criterion negated, the other aspects of the malignancy need to be at a later stage in development for visual identification. again, uncertainty leaves the differential open to potential distractors. clinical misdiagnosis has been reported in previous studies, with one showing that melanoma was included in the differential only 32% of the time for amelanotic melanomas vs 94% of the time for pigmented variants.7 late recognition could account for amelanotic melanomas presenting at a more advanced tumor stage, causing the higher mortality rates, as seen in our case and outlined in previous studies.3 the case we presented demonstrates the consequences of each aforementioned aspect of pm. throughout our case and those found in the literature, patients diagnosed with polypoid melanoma were seen months after the initial growth appeared. either from the patient’s own dismissal or through misdiagnosis, the lesions were biopsied only once they changed to a more aggressive growth pattern, with an average time to diagnosis being 15.6 months.8-12 our patient’s results staged her to be pt4b; having a > 4.0 mm thickness with ulceration. with the final diagnosis, our patient can proceed through the next steps of wide local excision, sentinel lymph node biopsy, and the possibility of adjuvant chemotherapy, both of which have been standard therapies. there is an unfortunate tendency to overlook melanomas when they are not confined to their typical presentation. lack of patient education and self-advocacy played an instrumental part in the 5 year long growth of this polypoid melanoma. also increased awareness of rare variants of melanoma across physician specialties, conclusion a. b. skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 253 especially in the realm of family medicine, could instill a lower biopsy threshold for indistinct growths and lead to quicker diagnosis and management. while the abcde algorithm is a staple when it comes to diagnosing melanoma, use of other modalities, such as the “ugly duckling sign,” and particularly for nodular melanoma the “efgs” (elevated, firm, growing), could be beneficial in early detection of these aggressively malignant subtypes. conflict of interest disclosures: none funding: none corresponding author: aleia boccardi, bs, ba 230 everhart street dupont, pa 18641 email: aleiamboccardi@gmail.com references: 1. plotnick h, rachmaninoff n, vandenberg hj jr. polypoid melanoma: a virulent variant of nodular melanoma. report of three cases and literature review. j am acad dermatol. 1990;23:880-4. 2. lideikaitė, a., mozūraitienė, j., & letautienė, s. (2017). analysis of prognostic factors for melanoma patients. acta medica lituanica, 24(1), 25–34. https://doi.org/10.6001/actamedica.v24i1.3460 3. thomas ne, kricker a, waxweiler wt, et al. comparison of clinicopathologic features and survival of histopathologically amelanotic and pigmented melanomas: a population-based study. jama dermatol.2014;150(12):1306– 1314. doi:10.1001/jamadermatol.2014.1348 4. kalkhoran s, milne o, zalaudek i, et al. historical, clinical, and dermoscopic characteristics of thin nodular melanoma. arch dermatol. 2010;146(3):311–318. doi:10.1001/archdermatol.2009.369 5. perniciaro c. dermatopathologic variants of malignant melanoma. mayo clin proc. 1997 mar;72(3):273-9. doi: 10.4065/72.3.273. pmid: 9070205. 6. manci ea, balch cm, murad tm, soong sj. polypoid melanoma, a virulent variant of the nodular growth pattern. am j clin pathol. 1981 jun;75(6):810-5. doi: 10.1093/ajcp/75.6.810. pmid: 7258141. 7. mcclain se, mayo kb, shada al, smolkin me, patterson jw, slingluff cl jr. amelanotic melanomas presenting as red skin lesions: a diagnostic challenge with potentially lethal consequences. int j dermatol. 2012 apr;51(4):420-6. doi: 10.1111/j.13654632.2011.05066.x. pmid: 22435430; pmcid: pmc4465919. 8. clark j, orge e, “polypoid pedunculated amelanotic melanoma.” the dermatologist vol 25, 8 (2017). 9. hikawa, renato shintani et al. “polypoid melanoma and superficial spreading melanoma different subtypes in the same lesion.” anais brasileiros de dermatologia vol. 89,4 (2014): 666-8. doi:10.1590/abd1806-4841.20142802 10. milani-nejad, n., scarbrough, c., mauzo, s. h, peters, s. b, bechtel, m. a, & carr, d. (2018). polypoid amelanotic melanoma: a diagnostic challenge. dermatology online journal, 24(8). retrieved from https://escholarship.org/uc/item/2160378m 11. di altobrando, ambra & patrizi, annalisa & dika, emi & savoia, francesco. (2020). cauliflowerlike exophytic mass on the skin: polypoid melanoma. clinical, dermoscopic, and histologic features. anais brasileiros de dermatologia. 95. 10.1016/j.abd.2020.04.010. 12. tan andrea, gutierrez d, brinster n, stein, j, “polypoid melanoma mistaken for verruca vulgaris; cleveland clinic journal of medicine september 2020, 87 (9) 534-536; doi: https://doi.org/10.3949/ccjm.87a.19079 skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 638 short communication traction alopecia in the beard jayvon mckinley1 and mindy kresch-vatch2 1department of dermatology, icahn school of medicine at mount sinai, new york, ny 2 new york medical college, valhalla, ny traction alopecia (ta) is a type of hair loss that results from recurring pulling on hair follicles. hairstyles such as dreadlocks and ponytails are believed to increase the risk of developing ta. due to its potential to be misdiagnosed as frontal fibrosing alopecia (ffa), alopecia areata, or patchy central centrifugal cicatricial alopecia (ccca), histopathology can help discriminate ta from these other diagnoses.1 early stages are distinguished by an elevated proportion of catagen and telogen hair follicles, whereas the later stages have a reduction in the terminal follicle count.2 without timely intervention, chronic ta could develop into scarring alopecia that may be unaffected by treatments. to avoid this irreversible course, it is crucial to focus on early prevention and therapeutic options. to date, most cases have been reported in the scalps of african american women.3 here we present a unique case of ta to the frontal chin area of a hasidic jewish male. a 27-year-old male with a history of eczema presented to our dermatology clinic for hair loss to the submental region of his beard (figure 1). hair loss first started one year ago and has gradually progressed since onset. he admits to frequent hair pulling, twisting, and braiding his beard. patient reports pruritus but denies any other localized symptoms. he denied any known allergies, systemic symptoms, or current medications. physical examination revealed a large patch of hair loss at the submental and frontal chin area. there was evidence of scarring at the frontal chin. patient was diagnosed with traction alopecia and advised to stop braiding his beard. figure 1. traction alopecia in the beard. three months post clinic visit, patient has noticed significant improvement in pruritus. introduction case report skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 639 he has ceased all twisting or pulling to the area. although he reports minimal hair regrowth so far, there has been no further loss of hair to the chin area. no medications or other treatments were used. patient will continue to minimize repetitive and extended tension to his hair. ta is a type of hair loss that, if left untreated, can result in permanent scarring alopecia – another indication that early diagnosis is critical. although most cases have been reported in african americans, it is believed that hair care practices are the cause of ta rather than hair type. this case report supports this pathophysiological argument by presenting a hasidic jewish male with ta to his chin area. prior literature has shown encouraging results of ta with triamcinolone acetonide, gashee lotion (a topical botanical formulation), 2% topical minoxidil, and oral minoxidil with fluocinonide 0.05% topical solution.3-6 in light of these promising therapeutic options, a large randomized, double-blind, placebo-controlled study is warranted to further evaluate the efficacy of these case-by-case situations. until there is additional data published regarding treatment options for ta, prevention and patient education remain the most important recourse. conflict of interest disclosures: none funding: none corresponding author: jayvon mckinley icahn school of medicine at mount sinai department of dermatology 5 e 98th st. 5th floor new york, ny 10029 email: jayvonbmckinley@gmail.com references: 1. billero v, miteva m. traction alopecia: the root of the problem. clin cosmet investig dermatol. 2018 apr 6;11:149-159. doi: 10.2147/ccid.s137296. pmid: 29670386; pmcid: pmc5896661. 2. pulickal jk, kaliyadan f. traction alopecia. [updated 2022 may 15]. in: statpearls [internet]. treasure island (fl): statpearls publishing; 2022 jan-. available from: https://www.ncbi.nlm.nih.gov/books/nbk470434/ 3. uwakwe ln, de souza b, tovar-garza a, mcmichael aj. intralesional triamcinolone acetonide in the treatment of traction alopecia. j drugs dermatol. 2020 feb 1;19(2):128-130. doi: 10.36849/jdd.2020.4635. pmid: 32129955. 4. umar s, carter mj. a multimodal hair-loss treatment strategy using a new topical phytoactive formulation: a report of five cases. case rep dermatol med. 2021 feb 4;2021:6659943. doi: 10.1155/2021/6659943. pmid: 33614172; pmcid: pmc7878086. 5. khumalo np, ngwanya rm. traction alopecia: 2% topical minoxidil shows promise. report of two cases. j eur acad dermatol venereol. 2007;21(3):433434. 6. kim sr, craiglow bg. treatment of traction alopecia with oral minoxidil. jaad case rep. 2022 apr 1;23:112-113. doi: 10.1016/j.jdcr.2022.03.023. pmid: 35495975; pmcid: pmc9039860. discussion skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 647 brief article papules on the helical rim: weathering nodules philip r. cohen, md1,2 1department of dermatology, university of california, davis medical center, sacramento, ca 2touro university california college of osteopathic medicine, vallejo, ca figure 1. weathering nodules on the helical rim of the left ear. a 64-year-old man presented with asymptomatic papules on both of his ears. he had extensive sun exposure since childhood and several actinic keratoses. however, he had no history of skin cancer. examination showed smooth, 2-to-3millimeter, whitish papules on the helical rim of the left ear (two papules) (figure 1) and right ear (one papule). the papules blanched when the clinician applied pressure to the adjacent helix. hence, the suspected diagnosis of weathering nodules was confirmed. the patient’s clinical information has been included in a prior publication.1 weathering nodules are small, skin-colored to white papules that can appear on the helices of typically older patients with a history of extensive sun exposure. when pressure is applied to the adjacent helical rim, weathering nodules blanch. this is referred to as a positive blanch sign.1,2 skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 648 the differential diagnosis of weathering nodules includes several other conditions: actinic keratosis, amyloidosis, basal cell carcinoma, calcinosis cutis, chondrodermatitis nodularis helicis, cutaneous b-cell lymphoma, cutaneous metastasis, elastotic nodule, gout, keratoacanthoma, rheumatoid nodule, sarcoidosis, squamous cell carcinoma, trichilemmomas, and verruca vulgaris. many of these conditions cannot be definitively established based on clinical appearance. therefore, a biopsy may be necessary to establish the diagnosis.1-4 in conclusion, the differential diagnosis of helical rim papules is diverse. many of the conditions can have a similar appearance. although a biopsy is frequently necessary to establish the diagnosis, weathering nodules may be differentiated from other causes of papules on the helical rim when a positive blanch sign is observed. conflict of interest disclosures: none funding: none corresponding author: philip r. cohen, md 10991 twinleaf court san diego, ca 92131 email: mitehead@gmail.com references: 1. udkoff j, cohen pr. a report of 10 individuals with weathering nodules and review of the literature. indian j dermatol. 2016;61(4):433-436. 2. udkoff j, cohen pr. using the blanch sign to differentiate weathering nodules from auricular tophaceous gout. cutis. 2016;98(6):392. 3. chabra i, singh r. gouty tophi on the ear: a review. cutis. 2013;92(4):190-192. 4. salah h, urso b, khachemoune a. review of the etiopathogenesis and management options of chondrodermatitis nodularis chronica helicis. cureus. 2018;10(3):e2367. mailto:mitehead@gmail.com deucravacitinib long-term efficacy and safety in plaque psoriasis: 2-year results from the phase 3 poetyk pso program richard b warren,1 howard sofen,2 shinichi imafuku,3 jacek c szepietowski,4 andrew blauvelt,5 lynda spelman,6 jessica toms,7 alex buck,7,8 subhashis banerjee,7 alan menter9 1dermatology centre, salford royal nhs foundation trust, nihr manchester biomedical research centre, the university of manchester, manchester, uk; 2ucla school of medicine and dermatology research associates, los angeles, ca, usa; 3fukuoka university hospital, fukuoka, japan; 4wroclaw medical university, wroclaw, poland; 5oregon medical research center, portland, or, usa; 6veracity clinical research, brisbane, qld, australia; 7bristol myers squibb, princeton, nj, usa; 8cytel inc, cambridge, ma, usa; 9baylor university medical center, dallas, tx, usa presented at the 2022 fall clinical dermatology conference; october 20—23, 2022; las vegas, nv this is an encore of the 2022 eadv spring symposium poster this poster may not be reproduced without written permission from the authors.email for richard b warren, bsc, mbchb, mrcp, phd: richard.warren@manchester.ac.uk synopsis • tyrosine kinase 2 (tyk2) is an intracellular enzyme that mediates signaling of cytokines (interleukin [il]-23 and type i interferons) involved in psoriasis pathogenesis1 • deucravacitinib, an oral, selective, allosteric tyk2 inhibitor, is approved by the us food and drug administration for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy2 — uniquely binds to the regulatory domain rather than to the more conserved catalytic domain where janus kinase (jak) 1/2/3 inhibitors bind (supplemental material)1 • findings from the phase 3 poetyk pso-1 and pso-2 trials in patients with moderate to severe plaque psoriasis showed that deucravacitinib was significantly more efficacious than placebo and apremilast based on the coprimary endpoints of ≥75% reduction from baseline in psoriasis area and severity index (pasi 75) and achievement of a static physician’s global assessment score of 0 (clear) or 1 (almost clear) with a ≥2-point improvement from baseline (spga 0/1) at week 16 and was well tolerated3,4 • clinical responses were maintained through 52 weeks in patients who received continuous deucravacitinib treatment and were improved in patients who switched from placebo to deucravacitinib at week 165 • patients completing the poetyk pso-1 and pso-2 trials could enroll in the poetyk long-term extension (lte) trial and receive open-label deucravacitinib 6 mg once daily objectives • the primary objective of this analysis was to characterize the safety and tolerability of long-term deucravacitinib use in patients with moderate to severe plaque psoriasis • the secondary objective was to characterize the maintenance of efficacy responses methods study designs • the study designs for poetyk pso-1, pso-2, and the lte are summarized in figure 1 • patients meeting the following key criteria were eligible to enroll in one of the parent studies: — age ≥18 years — diagnosis of moderate to severe plaque psoriasis x baseline pasi ≥12, spga ≥3, and body surface area (bsa) involvement ≥10% • patient randomization in poetyk pso-1 and pso-2 was stratified by geographic region, body weight, and prior biologic use • all patients were eligible to enter the poetyk lte after 52 weeks figure 1. poetyk pso-1, pso-2, and lte study designs 100 poetyk pso-1 and pso-2 deucravacitinib 6 mg qdplacebo (n = 166) deucravacitinib 6 mg qd<pasi 50 apremilast 30 mg bid≥pasi 50 titrate* p o e t y k p so -1 1 :2 :1 r an d o m iz at io n deucravacitinib 6 mg qd (n = 332) apremilast 30 mg bida (n = 168) deucravacitinib 6 mg qdplacebo (n = 255) deucravacitinib 6 mg qd (n = 511) deucravacitinib 6 mg qd<pasi 75 deucravacitinib 6 mg qd<pasi 75 deucravacitinib 6 mg qd ≥pasi 75 apremilast 30 mg bida (n = 254) ≥pasi 75 p o e t y k p so -2 1 :2 :1 r an d o m iz at io n cumulative exposure (weeks) 16 24 520 1 :1 deucravacitinib 6 mg qdplacebob deucravacitinib 6 mg qdplacebob primary endpoint b li n d e d s w it c h t o o p e n -l a b e l d e u c r a v a c it in ib open-label deucravacitinib 6 mg qd (n = 1221) poetyk lte 14856 60 68 76 88 112 124 1364 8 12 20 28 32 36 40 44 48 480 964 8 16 24 36 60 72 84exposure relative to lte (weeks) 1 year 2 yearsc aapremilast was titrated from 10 mg qd to 30 mg bid over the first 5 days of dosing. bupon relapse (≥50% loss of week 24 pasi percentage improvement from baseline), patients were to be switched to deucravacitinib 6 mg qd; due to a programming error, however, these patients continued on placebo until week 52. cdata were reported through the cutoff date of october 1, 2021. bid, twice daily; lte, long-term extension; pasi, psoriasis area and severity index; pasi 50, ≥50% reduction from baseline in pasi; pasi 75, ≥75% reduction from baseline in pasi; qd, once daily. outcome measures • safety outcomes included total adverse events (aes) and select aes of interest, including infections, herpes zoster, major adverse cardiovascular events (mace), venous thromboembolism (vte) events, and malignancies through the cutoff date of october 1, 2021 — to account for variable periods of treatment exposure, safety events are reported both as frequencies and as exposure-adjusted incidence rates (eairs) per 100 person-years (py) • efficacy endpoints included pasi 75, ≥90% reduction from baseline in pasi (pasi 90), and spga 0/1 responses through the cutoff date of october 1, 2021 • consistent with methodologies for assessing long-term outcomes in clinical trials of psoriasis therapies, 2 methods of imputation were used for sensitivity analyses6 — treatment failure rule (tfr): patients who discontinued treatment or the study due to worsening of psoriasis or lack of efficacy were imputed as nonresponders — modified nonresponder imputation (mnri): multiple imputation was used for patients with missing data, and patients who discontinued due to worsening of psoriasis were imputed as nonresponders; only patients who discontinued or reached week 60 by october 1, 2021, were included results patients • a total of 1519 patients received ≥1 dose of deucravacitinib across the parent trials and the poetyk lte, including 1364 patients in poetyk pso-1/pso-2 and 1221 patients in the poetyk lte • enrollment in the poetyk lte coincided with the peak of the covid-19 pandemic • baseline patient demographics and disease characteristics for the overall population are presented in table 1 exposure • the median exposure to deucravacitinib was 682 days • exposure data at 1 year and 2 years are presented in table 2 — exposure during weeks 0―52 of poetyk pso-1/pso-2 was 969.0 py, with an additional 1513.0 py of exposure during the poetyk lte — 1179 patients had ≥1 year (52 weeks) of continuous exposure and 584 had ≥2 years (104 weeks) of continuous exposure table 1. baseline patient demographics and disease characteristics in the parent trials parameter total (n = 1519) age, mean (sd), y 46.6 (13.4) weight, mean (sd), kg 90.6 (21.6) female, n (%) 493 (32.5) race, n (%) white 1325 (87.2) asian 153 (10.1) black or african american 23 (1.5) other 18 (1.2) age at disease onset, mean (sd), y 28.8 (14.9) disease duration, mean (sd), y 18.7 (12.7) pasi, mean (sd) 21.1 (8.1) spga, n (%) 3 (moderate) 1211 (79.7) 4 (severe) 308 (20.3) bsa involvement, mean (sd), % 26.2 (15.8) bsa, body surface area; pasi, psoriasis area and severity index; spga, static physician’s global assessment. table 2. extent of exposure to deucravacitinib continuous exposure, n (%) at 1 yeara at 2 yearsb deucravacitinib 6 mg qd (n = 1364) total py = 969.0 deucravacitinib 6 mg qd (n = 1519) total py = 2482.0 ≥52 weeks 503 (36.9) 1179 (77.6) ≥104 weeks — 584 (38.4) total exposure, n (%) ≥52 weeks — 1200 (79.0) ≥104 weeks — 606 (39.9) athis represents the pooled patient population of poetyk pso-1 and pso-2 (weeks 0―52). not all patients were receiving deucravacitinib 6 mg qd continuously throughout this period. bthis represents the pooled poetyk pso-1 and pso-2 population enrolled in the poetyk lte through the 120-day cutoff date of october 1, 2021. lte, long-term extension; py, person-years; qd, once daily. overall safety • a summary of overall safety with deucravacitinib, including the most common aes at 1 year and 2 years, is presented in table 3 — 2-year safety outcomes should be considered in the context of covid-19, as the timing of the poetyk lte coincided with the peak of the pandemic • a consistent ae profile was observed across poetyk pso-1, pso-2, and the lte, aside from covid-19 (table 3) • aes were predominantly mild or moderate in severity • an additional 8 deaths were reported in the poetyk lte up to the cutoff date — 6 of these deaths were due to covid-19, 1 was attributed to a ruptured thoracic aortic aneurysm (not drug related), and 1 was due to an unknown cause — mortality due to covid-19 was not higher than expected since the mortality rate was comparable to rates in the general population and a reference population (placebo arm of the johnson & johnson/janssen covid-19 vaccine trial) during the pandemic7 table 3. overall safety summary at 1 year vs at 2 years (as-treated population) at 1 yeara (poetyk pso-1 + pso-2) at 2 yearsb (poetyk pso-1 + pso-2 + lte) deucravacitinib 6 mg qd (n = 1364) total py = 969.0 deucravacitinib 6 mg qd (n = 1519) total py = 2482.0 ae category n (%) eair/100 py n (%) eair/100 py aes 995 (72.9) 229.2 1214 (79.9) 154.4 saes 55 (4.0) 5.7 145 (9.5) 6.1 discontinued treatment due to aes 43 (3.2) 4.4 69 (4.5) 2.8 deaths 2 (0.1) 0.2 10 (0.7) 0.4 most common aes (≥5% of patients) n (%) eair/100 py n (%) eair/100 py nasopharyngitis 229 (16.8) 26.1 271 (17.8) 12.9 upper respiratory tract infection 124 (9.1) 13.4 150 (9.9) 6.5 covid-19 5 (0.4) 0.5 124 (8.2) 5.1 headache 80 (5.9) 8.5 99 (6.5) 4.2 arthralgia 55 (4.0) 5.7 85 (5.6) 3.5 diarrhea 69 (5.1) 7.3 84 (5.5) 3.5 athis represents the pooled patient population of poetyk pso-1 and pso-2 (weeks 0―52). not all patients were receiving deucravacitinib 6 mg qd continuously throughout this period. bthis represents the pooled poetyk pso-1 and pso-2 population enrolled in the poetyk lte through the 120-day cutoff date of october 1, 2021. ae, adverse event; eair, exposure-adjusted incidence rate; lte, long-term extension; py, person-years; qd, once daily; saes, serious adverse events. aes of interest • the incidence rates for aes of interest were generally consistent with findings from clinical trials of other agents targeting similar pathways in patients with moderate to severe plaque psoriasis, after accounting for the different methodologies and time frames of those studies; rates were also comparable to real-world registry data (figure 2)8-23 • the incidence rates were similar at 1 year and 2 years, except for events related to covid-19 infection (table 4) • most covid-19 cases were not severe or serious and did not lead to treatment discontinuation — a total of 6 covid-19―related deaths were reported at 2 years, corresponding to an eair of 0.2/100 py (table 4) x this is comparable to the incidence of deaths in the placebo group (n = 19,544) of the johnson & johnson/janssen global vaccine study (0.23/100 py)7 — the majority of patients who experienced a covid-19―related serious ae (sae) had known or potential risk factors for severe illness from covid-19 (eg, diabetes mellitus, obesity, cardiovascular disease, lung disease, smoking) • the incidence rates for mace, vtes, and malignancies were low and in line with observations in poetyk pso-1 and pso-2 (table 4) • descriptions of vte events occurring during the study period are included in the supplemental material — none of these events were considered drug related • the ratio of basal cell cancer to squamous cell cancer remained close to 2:1 • the incidence rates for non–nonmelanoma skin cancers (non-nmscs) were not higher than expected in the psoriasis population or clinical trial safety data with approved agents24 — descriptions of the lymphoma cases are included in the supplemental material; all 3 patients with lymphoma had multiple confounding factors that made it difficult to attribute these events to treatment24 — other non-nmscs occurring at 2 years were not clustered to any particular malignancy type24 figure 2. eairs for serious infections, malignancies (excluding nmsc), and mace at 2 yearsa compared with long-term safety data, real-world data, or registry studies of other systemic psoriasis therapies serious infections 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 e a ir /1 0 0 p y ( 9 5 % c i) 2.6 (+covid-19) 0.9 (-covid-19) deucravacitinib (pso-1 & pso-2, lte) excluding covid-19 deucravacitinib (pso-1 & pso-2, lte) w ith covid-19 psoriasis background rate in registry clinical trials clinical trial long-term safety studies ustekinum ab guselkum ab risankizum ab secukinum ab optum labs – il-17 inhibitor optum labs – il-12/23 inhibitor optum – il-17 inhibitor optum – il-12/23 inhibitor optum – aprem ilast m arketscan – aprem ilast m arketscan – ustekinum ab badbir – ustekinum ab psolar – ustekinum ab psobest – ustekinum ab tofacitinib – psoriasis tofacitinib – psa tofacitinib – ra psoriasis background rate in real-world data malignancies (excluding nmsc) e a ir /1 0 0 p y ( 9 5 % c i) 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 0.5 d e u cravacitin ib e a ir /1 0 0 p y deucravacitinib (pso-1 & pso-2, lte) psoriasis background rate in registry clinical trial long-term safety studies ustekinum ab guselkum ab risankizum ab optum – il-17 inhibitor optum – il-12/23 inhibitor optum – aprem ilast m arketscan – all psoriasis m arketscan – adalim um ab m arketscan – etanercept m arketscan – general population pso lar – ustekinum ab psobest – ustekinum ab us seer database tofacitinib – psoriasis tofacitinib – psa tofacitinib – ra psoriasis background rate in real-world data clinical trials e a ir /1 0 0 p y ( 9 5 % c i) 0.0 0.5 1.0 1.5 2.0 2.5 3.0 0.4 d e u cravacitin ib e a ir /1 0 0 p y mace deucravacitinib (pso-1 & pso-2, lte) ustekinum ab guselkum ab risankizum ab secukinum ab optum – il-17 inhibitor (7) optum – il-12/23 inhibitor (7) optum – aprem ilast (7) pso lar – ustekinum ab psobest – ustekinum ab tofacitinib – psoriasis tofacitinib – psa tofacitinib – ra psoriasis background rate in registry clinical trial long-term safety studies psoriasis background rate in real-world data (claims data) clinical trials athis represents the pooled poetyk pso-1 and pso-2 population enrolled in the poetyk lte through the 120-day cutoff date of october 1, 2021. badbir, british association of dermatologists biologic and immunomodulators register; eair, exposure-adjusted incidence rate; il, interleukin; lte, long-term extension; mace, major adverse cardiovascular event; nmsc, nonmelanoma skin cancer; psa, psoriatic arthritis; psobest, german psoriasis registry; psolar, psoriasis longitudinal assessment and registry; py, person-years; ra, rheumatoid arthritis; seer, surveillance, epidemiology, and end results program. table 4. aes of interest at 1 year vs at 2 years (as-treated population) at 1 yeara (poetyk pso-1 + pso-2) at 2 yearsb (poetyk pso-1 + pso-2 + lte) deucravacitinib 6 mg qd (n = 1364) total py = 969.0 deucravacitinib 6 mg qd (n = 1519) total py = 2482.0 ae category n (%) eair/100 py n (%) eair/100 py serious infections 17 (1.2) 1.7 64 (4.2) 2.6 herpes zoster infection 9 (0.7) 0.9 18 (1.2) 0.7 total covid-19 infection 5 (0.4) 0.5 124 (8.2) 5.1 serious covid-19 infection 2 (0.1) 0.2 30 (2.0) 1.2 covid-19 pneumonia 0 (0) 0.0 13 (0.9) 0.5 covid-19—related deaths 0 (0) 0.0 6 (0.4) 0.2 macec 3 (0.2) 0.3 9 (0.6) 0.4 vted 2 (0.1) 0.2 3 (0.2) 0.1 total malignancies 10 (0.7) 1.0 22 (1.4) 0.9 nmsc 7 (0.5) 0.7 11 (0.7) 0.4 malignancies excluding nmsc 3 (0.2) 0.3 12 (0.8) 0.5 lymphoma 1 (0.1) 0.1 3 (0.2) 0.1 athis represents the pooled patient population of poetyk pso-1 and pso-2 (weeks 0―52). not all patients were on deucravacitinib 6 mg qd continuously throughout this period. bthis represents the pooled poetyk pso-1 and pso-2 population enrolled in the poetyk lte through the 120-day cutoff date of october 1, 2021. cmace is defined as cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. dvte is defined as pulmonary embolism and deep vein thrombosis. ae, adverse event; eair, exposure-adjusted incidence rate; mace, major adverse cardiovascular event; nmsc, nonmelanoma skin cancer; py, person-years; qd, once daily; vte, venous thromboembolism. efficacy • over 60 weeks of follow-up in the poetyk lte, the proportions of patients who achieved pasi 75, pasi 90, and spga 0/1 were similar regardless of which treatment they were receiving at week 52 in the parent study (table 5) • sensitivity analyses demonstrated the robustness of these results, with comparable response rates observed using the tfr, as-observed, or mnri method (table 5; figure 3) figure 3. clinical efficacy responses during poetyk lte weeks 0—60 in patients who were receiving deucravacitinib at week 52 in the parent study (sensitivity analysis): pasi 75a, pasi 90b, and spga 0/1c 77.7% 79.4% 75.7% 0 10 20 30 40 50 60 70 80 90 100 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 r e sp o n se r at e , % o f p at ie n ts weeks pasi 75 0 10 20 30 40 50 60 70 80 90 100 r e sp o n se r at e , % o f p at ie n ts 28 weeks 43.6% 49.6% 43.6% 70.8% 70.8% 50.7% 44.5% 71.3% tfr as observed mnriimputation method: 47.3% 0 4 8 12 16 20 24 32 36 40 44 48 52 56 60 pasi 90 tfr as observed mnriimputation method: 0 10 20 30 40 50 60 70 80 90 100 r e sp o n se r at e , % o f p at ie n ts 28 weeks 0 4 8 12 16 20 24 32 36 40 44 48 52 56 60 spga 0/1 tfr as observed mnriimputation method: 56.0% 58.7% 56.0% 60.0% 56.3% 57.1% patients, n 944tfr 805mnri 920 805 920 805 908 805 908 805 882 805 839 805 705 805 944as observed 919 920 905 903 875 829 690 apasi 75 responder defined as at least a 75% improvement from the parent study baseline in the pasi score. bpasi 90 responder defined as at least a 90% improvement from the parent study baseline in the pasi score. cspga 0/1 responder defined as an spga score of 0 or 1 with at least a 2-point improvement from parent study baseline. mnri: multiple imputation was used for patients with missing data, and patients who discontinued due to worsening of psoriasis only were imputed as nonresponders; includes patients who reached week 60 or discontinued by october 1, 2021. tfr: nri was implemented for patients who discontinued treatment or study due to worsening of psoriasis or lack of efficacy. mnri, modified nonresponder imputation; pasi 75, ≥75% reduction from baseline in psoriasis area and severity index; pasi 90, ≥90% reduction from baseline in pasi; spga 0/1, static physician’s global assessment score of 0 (clear) or 1 (almost clear) with a ≥2-point improvement from baseline; tfr, treatment failure rule. acknowledgments • this study was sponsored by bristol myers squibb • writing and editorial assistance was provided by liz rockstein, phd, of peloton advantage, llc, an open health company, parsippany, nj, usa, funded by bristol myers squibb • the authors also acknowledge julie scotto, bs, mph, for her contributions to this analysis conclusions • overall, the 2-year safety profile of deucravacitinib was consistent with weeks 0―52 of the poetyk pso-1 and pso-2 trials, and there were no emerging safety signals — the severity of aes continued to be predominantly mild or moderate, and the incidence of saes and aes leading to discontinuation remained low — the most common aes (≥5% of patients) included nasopharyngitis, upper respiratory tract infection, diarrhea, arthralgia, and headache — an increase in serious infections was observed, which is attributable to covid-19 infections due to the ongoing pandemic — no cases of herpes zoster were disseminated, serious, or led to treatment discontinuation — the overall malignancy incidence rate was largely in line with poetyk pso-1 and pso-2 and rates seen in other clinical trials and in real-world populations — there was a low incidence rate of cardiovascular events (eg, mace) that was comparable to long-term safety data from clinical trials with anti-il-12/23 or anti-il-23 agents and in real-world populations • unlike most other previous phase 3 trials, the poetyk studies were conducted in the context of the global covid-19 pandemic, and covid-19 rates increased from year 1 to year 2 — the overall incidence rates for covid-19 infection and covid-19―related hospitalization and death were consistent with background epidemiologic rates • clinical efficacy was maintained for up to 2 years with deucravacitinib treatment, regardless of which treatment was received at week 52 in the parent study — response rates at the start of the lte for pasi 75, pasi 90, and spga 0/1 were maintained at lte week 60 — consistent results were observed across tested imputation methods, including tfr, mnri, and as-observed data • these findings further support the use of deucravacitinib, a once-daily oral drug, as an effective and well-tolerated treatment for moderate to severe plaque psoriasis references and supplemental material scientific content on demand scan qr code via a barcode reader application disclosures rbw: research grants: abbvie, almirall, amgen, celgene, eli lilly, janssen, leo pharma, novartis, pfizer, and ucb; consulting fees: abbvie, almirall, amgen, biogen, boehringer ingelheim, celgene, dice, eli lilly, janssen, leo pharma, novartis, pfizer, sanofi, ucb, and union. hs: clinical investigator: abbvie, amgen, boehringer ingelheim, bristol myers squibb, eli lilly, janssen, leo pharma, novartis, and sun pharma. si: grants and personal fees: abbvie, eisai, janssen, kyowa kirin, leo pharma, maruho, sun pharma, taiho yakuhin, tanabe mitsubishi, and torii yakuhin; personal fees: amgen (celgene), boehringer ingelheim, bristol myers squibb, daiichi sankyo, eli lilly, novartis, and ucb. jcs: advisory board member/ consultant: abbvie, leo pharma, novartis, pierre-fabre, sanofi genzyme, and trevi; speaker: abbvie, eli lilly, janssen-cilag, leo pharma, novartis, and sanofi genzyme; investigator: abbvie, amgen, bristol myers squibb, galapagos, galderma, incyte, infrarx, janssen-cilag, manlo therapeutics, merck, novartis, pfizer, regeneron, trevi, and ucb. ab: scientific adviser and/or clinical study investigator: abbvie, abcentra, aligos, almirall, amgen, arcutis, arena, aslan, athenex, boehringer ingelheim, bristol myers squibb, dermavant, ecor1, eli lilly, evommune, forte biosciences, galderma, incyte, janssen, landos, leo pharma, novartis, pfizer, rapt, regeneron, sanofi genzyme, sun pharma, ucb, and vibliome. ls: consultant, paid investigator, and/or speaker: abbvie, amgen, anacor, ascend, astellas, astrazeneca, blaze bioscience, boehringer ingelheim, botanix, bristol myers squibb, celgene, dermira, eli lilly, galderma, genentech, glaxosmithkline, hexima, janssen, leo pharma, mayne pharma, medimmune, merck, merck-serono, novartis, otsuka, pfizer, phosphagenics, photon md, regeneron, roche, samumed, sanofi genzyme, shr, sun pharma anz, trius, ucb, and zai lab. jt and sb: employees and shareholders: bristol myers squibb. ab: contractor (through functional service provider cytel): bristol myers squibb. am: advisory board: abbott labs, amgen, boehringer ingelheim, janssen biotech, and leo pharma; consultant: abbott labs, amgen, eli lilly, janssen biotech, leo pharma, novartis, sun pharma, and ucb; honoraria: abbott labs, amgen, boehringer ingelheim, eli lilly, janssen biotech, leo pharma, novartis, sun pharma, and ucb; investigator: abbott labs, amgen, boehringer ingelheim, celgene, eli lilly, janssen biotech, leo pharma, merck, novartis, sun pharma, and ucb; research grants: abbott labs, amgen, boehringer ingelheim, celgene, janssen biotech, leo pharma, merck, and sun pharma; speaker: abbott labs, amgen, janssen biotech, leo pharma, sun pharma, and ucb. table 5. efficacy results at week 60 by imputation analysis deucravacitinib — deucravacitinib placebo — deucravacitinib apremilast — deucravacitinib total week 0 week 60 week 0 week 60 week 0 week 60 week 0 week 60 type of sensitivity analysis n mean response rate (%) n mean response rate (%) n mean response rate (%) n mean response rate (%) n mean response rate (%) n mean response rate (%) n mean response rate (%) n mean response rate (%) pasi 75 tfr 944 70.8 705 77.7 197 34.5 127 87.4 80 73.8 70 87.1 1221 65.1 902 79.8 mnri 805 71.3 805 75.7 138 37.0 138 87.4 79 74.7 79 84.8 1022 66.9 1022 78.1 as observed 944 70.8 690 79.4 197 34.5 124 89.5 80 73.8 70 87.1 1221 65.1 884 81.4 pasi 90 tfr 944 43.6 705 49.6 197 15.7 127 53.5 80 40.0 70 62.9 1221 38.9 902 51.2 mnri 805 44.5 805 47.3 138 17.4 138 54.2 79 40.5 79 60.1 1022 40.5 1022 49.3 as observed 944 43.6 690 50.7 197 15.7 124 54.8 80 40.0 70 62.9 1221 38.9 884 52.3 spga 0/1 tfr 944 56.0 705 58.7 197 25.4 126 65.1 80 53.8 70 72.9 1221 50.9 901 60.7 mnri 805 56.3 805 57.1 138 27.5 138 65.0 79 54.4 79 70.7 1022 52.3 1022 59.2 as observed 944 56.0 690 60.0 197 25.4 123 66.7 80 53.8 70 72.9 1221 50.9 883 61.9 tfr: nri was implemented for patients who discontinued treatment or study due to worsening of psoriasis or lack of efficacy. mnri: multiple imputation was used for patients with missing data, and patients who discontinued due to worsening of psoriasis only were imputed as nonresponders; includes patients who reached week 60 or discontinued by october 1, 2021. mnri, modified nonresponder imputation; pasi 75, ≥75% reduction from baseline in psoriasis area and severity index; pasi 90, ≥90% reduction from baseline in pasi; spga 0/1, static physician’s global assessment score of 0 (clear) or 1 (almost clear) with a ≥2% improvement from baseline; tfr, treatment failure rule. andrew blauvelt, md, mba,1 lawrence f. eichenfield, md,2 michael e. kuligowski, md, phd, mba,3 may e. venturanza, md,3 kang sun, phd,3 jonathan i. silverberg, md, phd, mph4 introduction ● atopic dermatitis (ad) is a chronic inflammatory skin disease characterized by itching, dryness, and redness1 ● treatments for ad include topical corticosteroids (tcs), topical calcineurin inhibitors (tci), and systemic immunomodulatory agents1 ● some topical treatments may be insufficient because of inadequate efficacy, delayed onset of efficacy, duration-of-use limitations, anatomic use restrictions, poor tolerability, and/or adverse reactions1,2 – tcs are associated with decreased skin thickness and elasticity (eg, striae); they are also not recommended for long-term application or use in sensitive areas – tci are associated with local reactions, such as stinging and burning ● ruxolitinib cream is a topical formulation of ruxolitinib, a selective inhibitor of janus kinase (jak) 1 and jak23 ● in two phase 3 randomized studies of identical design (true-ad1 [nct03745638] and true-ad2 [nct03745651]), ruxolitinib cream demonstrated anti-inflammatory activity with antipruritic action vs vehicle and was well tolerated in patients with ad3 objective ● to evaluate the long-term safety and disease control of ruxolitinib cream based on types of previous medication using pooled data from two phase 3 trials in patients with ad methods study design and patients ● eligible patients were aged ≥12 years with ad for ≥2 years and had an investigator’s global assessment (iga) score of 2 or 3 and 3%–20% affected body surface area (bsa), excluding scalp ● key exclusion criteria were unstable course of ad, other types of eczema, immunocompromised status, use of ad systemic therapies during the washout period and during the study, use of ad topical therapies (except bland emollients) during the washout period and during the study, and any serious illness or medical condition that could interfere with study conduct, interpretation of data, or patients’ well-being – the washout period for prior therapies was 1 week for topical ad treatments, 4 weeks for systemic corticosteroids or other immunomodulating agents, and 12 weeks or 5 half-lives for biologics ● true-ad1 and true-ad2 had identical study designs (figure 1) – in both studies, patients were randomized (2:2:1) to 1 of 2 ruxolitinib cream strength regimens (0.75% twice daily [bid], 1.5% bid) or vehicle cream bid for 8 weeks of double-blinded continuous treatment (vehicle-controlled [vc] period); patients were instructed to continue treating lesions even if they improved – patients on ruxolitinib cream subsequently continued treatment for 44 weeks (long-term safety [lts] period); patients initially randomized to vehicle were rerandomized 1:1 (blinded) to either ruxolitinib cream regimen ■ during the lts period, patients were instructed to treat skin areas with active ad only and stop treatment 3 days after clearance of lesions; patients were to restart treatment with ruxolitinib cream at the first sign of recurrence figure 1. study design • continuous treatment for 8 weeks • rescue treatment not permitted • treat as needed for 44 weeks • stop treatment 3 days after lesion clearance • rescue treatment not permitted vehicle-controlled period long-term safety period patients initially randomized to rux remain on their regimen patients on vehicle rerandomized 1:1 to 0.75% rux bid or 1.5% rux bid patients randomized 2:2:1 rux† visits every 4 weeks week 52day 1 week 8 recurrence of lesions clearance of lesions 1.5% rux bid (n=~240 in each study) 0.75% rux bid (n=~240 in each study) vehicle bid (n=~120 in each study) ad, atopic dermatitis; bid, twice daily; bsa, body surface area; rux, ruxolitinib cream. † patients self-evaluated recurrence of lesions between study visits and treated lesions with active ad (≤20% bsa). if lesions cleared between study visits, patients stopped treatment 3 days after lesion disappearance. if new lesions were extensive or appeared in new areas, patients contacted the investigator to determine if an unscheduled additional visit was needed. 1oregon medical research center, portland, or, usa; 2departments of dermatology and pediatrics, university of california san diego, san diego, ca, usa; 3incyte corporation, wilmington, de, usa; 4george washington university, washington, dc, usa assessments ● disease control was assessed by the proportion of patients who achieved no or minimal skin lesions (iga score of 0 or 1 [clear or almost clear skin]) and mean percentage of bsa affected by ad at each visit (every 4 weeks) during the lts period ● safety and tolerability assessments included the frequency of reported treatment-emergent adverse events (teaes), treatment-related adverse events, and adverse events (aes) leading to treatment discontinuation statistical analysis ● all analyses were conducted using the pooled data from both studies – the disease control analysis included patients who remained on their initial ruxolitinib cream strength regimen from the vc period through the lts period; data are reported as observed – the safety analysis included patients who received ruxolitinib cream in any period (vc or lts) ● data were summarized using descriptive statistics results patients ● a total of 1249 patients (median age, 32 years) were randomized in the vc period, and 1072 continued in the lts period (vehicle to ruxolitinib cream, n=200 [101 to 0.75% and 99 to 1.5%]; 0.75% ruxolitinib cream, n=426; 1.5% ruxolitinib cream, n=446) ● distribution of baseline demographics and clinical characteristics was similar across treatment groups (table 1) table 1. patient demographics and baseline clinical characteristics characteristic vehicle (n=250) 0.75% rux (n=500) 1.5% rux (n=499) total (n=1249) age, median (range), y 34.0 (12–82) 33.0 (12–85) 31.0 (12–85) 32.0 (12–85) female, n (%) 159 (63.6) 304 (60.8) 308 (61.7) 771 (61.7) race, n (%) white 170 (68.0) 345 (69.0) 355 (71.1) 870 (69.7) black 61 (24.4) 118 (23.6) 113 (22.6) 292 (23.4) asian 10 (4.0) 16 (3.2) 20 (4.0) 46 (3.7) other 9 (3.6) 21 (4.2) 11 (2.2) 41 (3.3) region, n (%) north america 172 (68.8) 342 (68.4) 341 (68.3) 855 (68.5) europe 78 (31.2) 158 (31.6) 158 (31.7) 394 (31.5) bsa, mean (sd), % 9.6 (5.5) 10.0 (5.3) 9.6 (5.3) 9.8 (5.4) easi, mean (sd) 7.8 (4.8) 8.1 (4.9) 7.8 (4.8) 8.0 (4.8) iga, n (%) 2 64 (25.6) 125 (25.0) 123 (24.6) 312 (25.0) 3 186 (74.4) 375 (75.0) 376 (75.4) 937 (75.0) itch nrs score, mean (sd) 5.1 (2.4) 5.2 (2.4) 5.1 (2.5) 5.1 (2.4) ≥4, n (%) 159 (63.6) 324 (64.8) 315 (63.1) 798 (63.9) duration of disease, median (range), y 16.5 (0.8–79.1) 15.1 (0.1–68.8) 16.1 (0–69.2) 15.8 (0–79.1) facial involvement, n (%)* 93 (37.2) 195 (39.0) 197 (39.5) 485 (38.8) number of flares in last 12 mo, mean (sd)* 7.3 (25.7) 5.2 (6.7) 6.0 (17.6) 5.9 (16.5) bsa, body surface area; easi, eczema area and severity index; iga, investigator’s global assessment; nrs, numerical rating scale; rux, ruxolitinib cream. * patient reported. disease control ● at each visit in the lts, most patients in the 0.75% or 1.5% ruxolitinib cream groups had an iga score of 0/1 (clear or almost clear), regardless of the type of previous medication (figure 2) ● regardless of type of previous medication, mean affected bsa was low (generally <3%) during the lts among patients who applied 0.75% or 1.5% ruxolitinib cream (figure 3) figure 2. patients achieving iga 0/1 stratified by the type of previous medication among patients who applied (a) 0.75% or (b) 1.5% ruxolitinib cream n n 93 n 321 84 n n 82 30 89 311 82 81 28 88 301 81 79 28 78 279 72 72 25 78 270 71 70 25 72 254 65 62 21 71 250 65 60 22 78 257 72 65 20 79 265 72 67 23 80 262 73 70 23 83 266 76 73 24 a) 0.75% ruxolitinib cream 40 50 60 70 0 10 20 30 80 90 12 16 20 24 28 32 36 40 44 48 52 pa tie nt s w ith c le ar o r a lm os t c le ar s ki n (ig a of 0 o r 1 ), % time, wk 77.1 75.9 76.3 68.5 62.5 tcs tci tcs+tci systemic phototherapy n n 92 n 325 82 n n 83 38 92 318 82 81 38 91 312 81 80 38 87 297 77 74 36 77 281 68 66 31 68 271 59 66 28 75 276 66 69 33 74 268 65 66 34 82 280 73 72 35 82 262 74 67 33 86 276 77 71 33 b) 1.5% ruxolitinib cream 40 50 60 70 0 10 20 30 80 90 12 16 20 24 28 32 36 40 44 48 52 pa tie nt s w ith c le ar o r a lm os t c le ar s ki n (ig a of 0 o r 1 ), % time, wk tcs tci tcs+tci systemic phototherapy 79.0 77.9 76.7 66.7 78.9 iga, investigator’s global assessment; tci, topical calcineurin inhibitor; tcs, topical corticosteroid. figure 3. mean affected bsa stratified by the type of previous medication among patients who applied (a) 0.75% or (b) 1.5% ruxolitinib cream n n 93 n 321 84 n n 82 30 89 311 82 81 28 88 301 81 79 28 80 281 74 73 26 78 271 71 70 25 72 255 65 62 21 72 251 66 60 22 78 257 72 65 20 79 266 72 68 23 80 263 73 71 24 83 266 76 73 24 a) 0.75% ruxolitinib cream 0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 12 16 20 24 28 32 36 40 44 48 52 m ea n to ta l a ffe ct ed b sa , % time, wk 1.8 2.5 2.4 2.7 2.6 n n 92 n 325 82 n n 83 38 92 318 82 81 38 91 312 81 80 38 87 297 77 74 36 77 281 68 67 32 68 271 59 66 28 75 276 66 69 33 74 269 65 66 34 82 280 73 72 35 82 263 74 67 33 86 277 77 71 34 b) 1.5% ruxolitinib cream 0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 12 16 20 24 28 32 36 40 44 48 52 m ea n to ta l a ffe ct ed b sa , % time, wk tcs tci tcs+tci systemic phototherapy tcs tci tcs+tci systemic phototherapy 1.3 1.9 2.0 1.9 1.7 bsa, body surface area; tci, topical calcineurin inhibitor; tcs, topical corticosteroid. safety ● ruxolitinib cream was well tolerated across all subgroups of previous treatment; the frequency of application site reactions was low (table 2) ● in the overall population, the most common teaes through week 52 were upper respiratory tract infection, nasopharyngitis, and headache – no aes suggestive of a relationship to systemic exposure were observed table 2. adverse events according to the type of previous medication among patients who applied ruxolitinib cream in the phase 3 studies (vc or lts periods) parameter tcs tci tcs+tci systemic therapies phototherapy patients, n 0.75% rux 461 134 121 106 42 1.5% rux 461 121 109 110 48 teaes, n (%) 0.75% rux 286 (62.0) 97 (72.4) 87 (71.9) 80 (75.5) 30 (71.4) 1.5% rux 270 (58.6) 85 (70.2) 80 (73.4) 76 (69.1) 38 (79.2) application site reactions, n (%) 0.75% rux 15 (3.3) 5 (3.7) 4 (3.3) 3 (2.8) 2 (4.8) 1.5% rux 9 (2.0) 4 (3.3) 4 (3.7) 4 (3.6) 2 (4.2) traes, n (%) 0.75% rux 36 (7.8) 18 (13.4) 15 (12.4) 13 (12.3) 8 (19.0) 1.5% rux 35 (7.6) 19 (15.7) 19 (17.4) 15 (13.6) 7 (14.6) teaes resulting in discontinuation, n (%) 0.75% rux 8 (1.7) 1 (0.7) 1 (0.8) 3 (2.8) 1 (2.4) 1.5% rux 4 (0.9) 1 (0.8) 1 (0.9) 1 (0.9) 0 serious teaes, n (%) 0.75% rux 15 (3.3) 3 (2.2) 3 (2.5) 6 (5.7) 1 (2.4) 1.5% rux 10 (2.2) 2 (1.7) 2 (1.8) 1 (0.9) 1 (2.1) lts, long-term safety; rux, ruxolitinib cream; tci, topical calcineurin inhibitor; tcs, topical corticosteroid; teae, treatment-emergent adverse event; trae, treatment-related adverse event; vc, vehicle controlled. conclusions ● ruxolitinib cream, used as maintenance therapy, demonstrated effective long-term disease control, regardless of the type of previous therapy ● ruxolitinib cream was well tolerated over a period up to 52 weeks, regardless of the type of previous therapy disclosures ab has served as a scientific advisor and/or clinical study investigator for abbvie, abcentra, aligos, almirall, amgen, arcutis, arena, aslan, athenex, boehringer ingelheim, bristol myers squibb, dermavant, eli lilly and company, evommune, forte, galderma, incyte corporation, janssen, landos, leo pharma, novartis, pfizer, rapt, regeneron, sanofi genzyme, sun pharma, and ucb pharma. lfe has served as an investigator, consultant, speaker, or data safety monitoring board member for abbvie, almirall, arcutis, asana, dermavant, eli lilly, forte biosciences, galderma, ichnos/glenmark, incyte corporation, janssen, leo pharma, novartis, ortho dermatologics, otsuka, pfizer, regeneron, and sanofi genzyme. mev and ks are employees and shareholders of incyte corporation. mek was an employee and shareholder of incyte corporation at the time of development of the original presentation. jis has received honoraria for advisory board, speaker, and consultant services from abbvie, asana, bluefin, boehringer ingelheim, celgene, dermavant, dermira, eli lilly, galderma, glaxosmithkline, glenmark, incyte corporation, kiniksa, leo pharma, menlo therapeutics, novartis, pfizer, realm, regeneron, and sanofi and research grants for investigator services from galderma and glaxosmithkline. acknowledgments the authors thank the patients, investigators, and investigational sites whose participation made the study possible. support for this study was provided by incyte corporation (wilmington, de, usa). writing assistance was provided by joshua solomon, phd, an employee of icon (north wales, pa, usa), and was funded by incyte corporation. references 1. langan sm, et al. lancet. 2020;396(10247):345-360. 2. eichenfield lf, et al. j am acad dermatol. 2014;71(1):116-132. 3. papp k, et al. j am acad dermatol. 2021;85(4):863-872. long-term safety and disease control with ruxolitinib cream among patients with atopic dermatitis based on previous medication history: pooled results from two phase 3 studies presented at the fall clinical dermatology conference las vegas, nv • october 21–24, 2021 to download a copy of this poster, scan code. skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 829 brief article cutaneous prostate adenocarcinoma masquerading as cellulitis ariel darnall, do1, rebecca c. olsen, ms2, dathan hamann, md1,3, sarah estrada, md4 1honorhealth dermatology residency, scottsdale, az 2a.t. still university school of osteopathic medicine in arizona, phoenix, az 3contact dermatitis institute, phoeniz, az 4affiliated dermatology, scottsdale, az prostate cancer is the second leading cause of cancer deaths and accounts for approximately 211,893 new cancer cases per year, making it the most common malignancy in men.1 prostate cancer frequently metastasizes to nearby lymph nodes and bone, particularly the lumbar spine via the batson plexus, a portal-like venous system between the prostate and lower vertebrae. other common sites of hematogenous spread include the liver, lung, and pleura. cutaneous metastases account for only ≤0.36% of known prostatic cancer metastasis cases, often localizing to the lower abdomen, thigh, and scrotal regions.2 the case being presented describes a patient with a history of metastatic prostate carcinoma who was evaluated for a suprapubic rash that was later diagnosed as a cutaneous metastasis. a 64-year-old male with a history of metastatic prostate carcinoma presented to the emergency department for evaluation of a unilateral suprapubic rash of 2-week duration. the rash was asymptomatic, originating as a small nodular lesion that progressively enlarged and became erythematous and indurated. he was admitted for a presumed skin infection with initial therapy of broad-spectrum antibiotics. the patient was diagnosed with prostatic adenocarcinoma two years prior with an abstract cutaneous metastases of prostate cancer are a rare entity and mimic many other common cutaneous conditions such as cellulitis, zosteriform lesions, and many others, making it easy to misdiagnose. recognition of this condition is vital to prevent delays in treatment, as lesions usually appear in late stages of the disease and are associated with a high fatality rate. here we describe a case of a 64-year-old man with a history of diffuse metastatic prostate carcinoma, who presented with a suprapubic rash that was initially diagnosed as cellulitis but was later determined to be cutaneous metastasis. clinical characteristics of this metastasis and common dermal lesions with similar clinical presentations are discussed. clinicians should be aware of the characteristics of this cutaneous metastasis and consider it when evaluating skin lesions that mimic soft tissue infections. introduction case report skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 830 initial psa of 298. computed tomography of the abdomen and pelvis at the time of diagnosis showed sclerotic lesions throughout the skeleton with prominent lymphadenopathy involving the retroperitoneum, bilateral iliac chains, and left groin consistent with metastatic disease. the patient received chemotherapy treatment after initial diagnosis. one month prior to rash presentation, magnetic resonance imaging of the brain revealed diffuse metastasis which was treated with whole brain radiation. on examination, a non-tender, firm to hard erythematous plaque with overlying crust was noted along the right suprapubic region (figure 1) with extension to the penile base. penile and scrotal edema were noted. a punch biopsy was obtained from the lesion. histopathology revealed metastatic adenocarcinoma of prostate origin with evidence of lymphovascular invasion (figure 2). staining was positive for cytokeratin ae1/ae3 and nkx 3.1 (figure 3). a diagnosis of cutaneous metastasis of prostatic adenocarcinoma was made based on these findings. cutaneous metastases of prostate cancer are rare and frequently mimic other conditions such as cellulitis, sebaceous cysts, telangiectasias, zosteriform lesions, lipomas, and furuncles/carbuncles, and frequently are misdiagnosed leading to inappropriate antibiotic treatment.3 breast cancer is the most common form of malignancy to metastasize to the skin, whereas prostate cancer is the least likely.4 it is critical to consider cutaneous metastasis as a differential diagnosis to prevent delayed treatment. cutaneous metastases tend to appear in later stages of the disease and many patients pass away within one year of occurence.2 additionally, cutaneous metastasis can be the first indication of extranodal metastatic disease, potentially appearing before an internal malignancy is detected.5 figure 1. clinical image of lesion illustrating a firm erythematous and indurated plaque with some overlying crust. the gross appearance of prostatic adenocarcinoma metastasis is inconsistent, and patients may report pain to no symptoms at all.2 the metastasis typically presents as several rubbery pink to violaceous nodules, indurated plaques with a peau d’orange appearance, or telangiectatic plaques but can also appear as edema or a generalized rash.2,5 to distinguish metastasis from other dermatological conditions, the lesion(s) should be biopsied and histologically examined. specimens should be stained with immunohistochemical markers to aid in diagnosis. the tumor suppressor gene, nkx3.1 has been shown to be highly sensitive (98.6%) and specific (99.7%) for metastatic prostate adenocarcinoma.6 cytokeratin ae1/ae3 is a marker for epithelial differentiation in malignant tumors discussion skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 831 figure 2. (a) medium power view of a punch biopsy of the lesion showing irregular epidermal hyperplasia and a conspicuous grenz zone with overlying infiltrate arranged as strands and cords through a sclerotic dermis. (b) high power view displaying lymphovascular invasion. figure 3. (a) cytokeratin ae1/ae3 immunostain is strongly positive within the neoplastic infiltrate supporting epithelial origin. (b) nkx3 immunostain highlighting the malignant cells strongly supporting a diagnosis of metastatic adenocarcinoma. that are not well differentiated and can help offer insight on tumor behavior.7 staining for prostate specific membrane antigen (psma), a type-2 integral membrane protein may also be beneficial in diagnosis. however, psma can be present in both benign and malignant prostatic tissue and high psma expression does not necessarily indicate a highly aggressive tumor.8 the tissue sample in the presented case stained positive for psma but was omitted for this reason. utilizing palpation and tissue texture changes during the physical examination can aid in diagnosis. on deep palpation, skin metastases may feel tender, firm, indurated, and rope-like in texture9, these types of clinical signs suggest a need for further workup. palpation alone is often insufficient for skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 832 diagnosis, which is why skin biopsy and immunohistological evaluation is recommended.10 cellulitis, an acute infection of the dermis and subcutaneous tissues commonly caused by staphylococcus aureus or streptococcus species infections, appears as an expanding, warm, tender, edematous and erythematous area without sharp borders.11 as cellulitis is relatively common and clinical signs are not pathognomonic, it is frequently misdiagnosed leading to roughly 130,000 unnecessary hospitalizations every year.11 the diagnosis relies solely on a clinician’s ability to recognize cellulitis as there are no accurate laboratory or imaging tests at this time.11 data suggests that approximately 30% of cellulitis patients are misdiagnosed and receive unnecessary antibiotic treatment.12 a zosteriform pattern describes cutaneous lesions that are localized and distributed unilaterally within a dermatome, an area of skin corresponding to sensory nerves that all originate from a single nerve root.10 the pattern is classically attributed to herpes zoster infections, which occur after recrudescence of varicella-zoster viral infections. this is frequently observed as a painful zosteriform pattern in a v-shape on the back or as a s-shape along the anterolateral aspect of the trunk.10 although cutaneous metastases of prostate cancer rarely present as zosteriform lesions, if this type of skin lesion is present for over 14 days, primary skin cancers and to a lesser extent, cutaneous metastases of internal malignancies, should be considered in the clinical differential. in a study of 15 cases of cutaneous zosteriform metastases, seven of the cases were initially misdiagnosed as a herpes zoster infection and treated with antiviral medications.10 the variable presentation of cutaneous metastases of prostate cancer makes it difficult to diagnose, often resulting in delayed or improper treatment. as skin metastasis is a rare form of this malignancy and lesions may mimic other dermatologic conditions, this may be the basis for frequent misdiagnosis. to accurately distinguish cutaneous prostatic metastases from other conditions, a through history and physical exam focusing on palpation and tissue texture, combined with supportive diagnostics, can guide clinicians in differentiating malignancy from other benign skin conditions. conflict of interest disclosures: none funding: none corresponding author: ariel darnall, do honorhealth dermatology 7400 e thompson peak pkwy scottsdale, az 85255 phone: (480) 773-4898 email: ariel.kerry.gnazzo@gmail.com references: 1. u.s. cancer statistics working group. u.s. cancer statistics data visualizations tool, based on 2020 submission data (1999-2018): u.s. department of health and human services. centers for disease control and prevention and national cancer institute website. updated june 2021. accessed january 2022. www.cdc.gov/cancer/dataviz 2. dills a, obi o, bustos k, et al. cutaneous metastasis of prostate adenocarcinoma: a rare presentation of a common disease. j investig med high impact case rep. 2021;9:2324709621990769. 3. brown gt, patel v, lee cc. cutaneous metastasis of prostate cancer: a case report and review of the literature with bioinformatics analysis of multiple healthcare delivery networks. j cutan pathol. 2014;41(6):524-528. conclusion http://www.cdc.gov/cancer/dataviz skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 833 4. krathen ra, orengo if, rosen t. cutaneous metastasis: a meta-analysis of data. south. med. j. 2003;96(2): 164-167. 5. araújo e, barbosa m, costa r, sousa b, costa v. a first sign not to be missed: cutaneous metastasis from breast cancer. eur j case rep intern med. 2020;7(1):001356. 6. gurel b, ali tz, montgomery ea, et al. nkx3.1 as a marker of prostatic origin in metastatic tumors. am j surg pathol. 2010;34(8):10971105. 7. miller rt. cytokeratin ae1/ae3. propath. updated november 2003. accessed march 21, 2022. https://www.who.int/medical_devices/diagnostics/ selection_in-vitro/selection_in-vitromeetings/00038_05_focus_nov_2003.pdf 8. ferraro da, rüschoff jh, muehlematter uj, et al. immunohistochemical psma expression patterns of primary prostate cancer tissue are associated with the detection rate of biochemical recurrence with 68ga-psma-11 pet. theranostics. 2020;10(14):6082-6094. 9. gorman bg, hanson j, vidal ny. the importance of palpation in the skin cancer screening examination. j. cosmet. dermatol. 2021;20(12): 3982-3985. 10. el hayderi l, libon f, nikkels-tassoudji n, et al. zosteriform dermatoses-a review. glob dermatol. 2015;2(4):163-173. 11. ko ln, garza-mayers ac, st john j, et al. effect of dermatology consultation on outcomes for patients with presumed cellulitis: a randomized clinical trial. jama dermatol. 2018;154(5):529536. 12. sullivan t, de barra e. diagnosis and management of cellulitis. clin med (lond). 2018;18(2):160-163. skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 824 brief article psoriatic arthritis flare in a hospitalized patient with schizoaffective disorder: a case report puneet arora, bs1, tracy a. tomac, md2 1university of minnesota medical school, minneapolis, mn 2regions hospital, st. paul, mn psoriasis is a common immune-mediated inflammatory skin condition that affects at least 1% of adults in the united states.1 the disease ranges in severity from limited erythematous, pruritic plaques to involvement of all surfaces if left untreated. among these patients, it is estimated that up to 41% also experience psoriatic arthritis, a progressive inflammatory arthritis that can result in permanent disability.2 in recent years, anti-il-17a agents such as ixekizumab and secukinumab have been shown to improve symptoms in patients with active psoriatic arthritis unresponsive to traditional first-line tnf inhibitors.3 in recent years, large studies have observed an increased prevalence of psoriasis in patients with schizophrenia spectrum disorders (3.3%) and broadly unspecified psychosis (35%).4 several studies have found that the risk of psoriasis among patients with schizophrenia is significantly higher than in those without it, possibly explained by t helper 17 (th17) activation, the main immunological trigger of psoriasis.5,6 due to the nature of severe psychiatric illnesses, patient’s length of stay in the hospital can vary greatly from 72-hour abstract psoriasis is a known comorbid condition in patients with schizophrenia spectrum disorders. due to the nature of these psychiatric conditions, many experience lengthy hospitalizations and self-isolate at baseline, which can make identification and management of psoriasis difficult. we report the case of a middle-aged male with a history of schizoaffective disorder and treatment-resistant psoriatic arthritis who experienced a severe flare while hospitalized. his two-month hospital stay became complicated by combative behavior and continued medication refusal, resulting in repeated seclusion events and eventual transfer to a higher acuity unit. after treatment with ixekizumab and a course of prednisone was initiated one month after admission and symptom onset, the patient’s lesions were tremendously improved along with his mood on the unit. with the improvement in his chronic pain and discomfort, the patient was able to focus on mental health recovery and rapidly approached discharge. this report highlights the importance of appropriate management of comorbid conditions, especially psoriasis in patients with schizophrenia spectrum disorders needing long-term hospitalization. additionally, this case demonstrates the successful use of ixekizumab in treatment-resistant psoriasis. introduction skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 825 holds to several months. therefore, appropriate management of co-existing conditions like psoriasis becomes crucial. a middle-aged male with a history of schizoaffective disorder and psoriatic arthritis was admitted to the hospital for paranoia and suicidal ideation. historically, his psychiatric health had been maintained with valproic acid and haloperidol. however, his valproic acid level was 16 mcg/ml (therapeutic range: 50-100 mcg/ml) on admission, indicating nonadherence. it was learned that the patient had previously failed several biologic medications including tnf (adalimumab, etanercept), jak (tofacitinib) and pde (apremilast) inhibitors. while the arthritic component of the patient’s psoriasis had been mostly stable on adalimumab for 7 months, ixekizumab had ultimately been prescribed prior to the current admission to provide better relief from his skin lesions. two days after admission, he began experiencing severe joint pain in his shoulders, fingers, knees, and feet. this pain was persistent and minimally relieved by acetaminophen. his course was complicated over the next two weeks by combative behavior requiring seclusion or restraints almost daily and neuroleptic medication refusal. ultimately, the patient was transferred to a higher acuity unit. on physical exam, several new and large erythematous plaques with scale were observed on his palmar/dorsal hands, wrists, knees, ankles, feet, and gluteal cleft in addition to limited range of motion diffusely due to chronic joint pain (pasi score: 11.1, figure 1a). there was moderate pitting and discoloration of the nails; no joint deformities were appreciated. unfortunately, his ixekizumab had not been filled as the patient was hospitalized. as this newer medication was not on formulary at the hospital, arrangements were made for his family to fill it at a specialty pharmacy and the patient received the loading dose a month after symptom onset. a course of oral prednisone 10mg and a topical betamethasone/calcipotriene formulation were also utilized. two days after starting the course of prednisone, the patient began endorsing nightly auditory hallucinations involving two voices speaking to one another, causing him distress. these voices continued until the course was tapered to 5mg after a week and eventually discontinued. two weeks after receiving the 160mg im loading dose of ixekizumab and completing the course of prednisone, the patient’s lesions were tremendously improved and fading in all noted regions (figure 1b). importantly, his mood and irritability on the unit improved as the chronic joint pain had become manageable and he rapidly approached readiness for discharge. with this multidisciplinary effort from his dermatologic and psychiatric physicians, the patient became more receptive to continuing the former valproic acid and haloperidol regimen that had been successful for him. within one month, he was transferred to an intensive residential treatment center where he was able to focus on mental health recovery. this case demonstrates the importance of appropriate management of comorbid conditions, especially psoriasis in patients with schizophrenia spectrum disorders needing long-term hospitalization. timely case report discussion skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 826 figure 1. numerous erythematous plaques with scale on the dorsal surface of the patient’s hands one month after admission (a), which improved two weeks after initiating treatment (b). skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 827 care is crucial to limit unnecessary suffering and extended hospital stay in these patients. appropriate treatment may even promote medication adherence overall and limit future hospitalizations for both their dermatologic and psychiatric conditions. this may be more challenging in cases involving behavioral volatility, seclusion or restraint placement, floor transfers and extensive self-isolation such as in the one presented. therefore, effective interdisciplinary communication becomes paramount and clinicians should ensure that investigation into the causes of patient discomfort are not limited to within their psychiatric diagnoses. the benefit on both the psoriatic joint pain and extensive plaques from the 2016 fda approved biologic ixekizumab was noted in our patient, lasting beyond the effects of the prednisone burst. ixekizumab is a selective inhibitor of il-17a indicated for moderate to severe plaque psoriasis that has been shown to be equal or superior to other biologic therapies in efficacy, patient adherence and cost.7 while a recent retrospective study found both ixekizumab and the similar il-17a antagonist secukinumab to be highly effective for the short and long-term treatment of psoriasis, further studies exploring the efficacy of these medications in treatment-resistant patients is needed.8 both medications have the benefit of monthly im dosing, an important consideration in patients with history of inconsistent adherence. in this case, the patient also experienced new auditory hallucinations beginning 2 days after initiating prednisone which continued until the course was tapered and eventually discontinued. while the overall prevalence of severe neuropsychiatric symptoms (psychosis, mood fluctuations) in those receiving glucocorticoids has been estimated to be 6%, patients in this population may be more susceptible.9 in conclusion, clinicians caring for patients with schizophrenia spectrum disorders, particularly in cases requiring long-term hospitalization should be aware of the increased prevalence of psoriasis in this population to prevent delays in treatment. care should be taken to ensure that irritability, self-isolation and other related behaviors are not always assumed to be linked to their psychiatric diagnoses. additionally, anti-il-17a agents such as ixekizumab can provide significant relief for psoriatic arthritis patients that have failed previous treatments. conflict of interest disclosures: none funding: none corresponding author: puneet arora, bs 516 delaware st. se, mail code 98 phillips-wangensteen bldg, suite 1-400 minneapolis, mn 55455 phone: (612) 625-8625 email: arora103@umn.edu references: 1. parisi r, symmons dpm, griffiths cem, ashcroft dm. global epidemiology of psoriasis: a systematic review of incidence and prevalence. j invest dermatol. 2013;133(2):377-385. doi:10.1038/jid.2012.339 2. ogdie a, yu yd, haynes k, et al. risk of major cardiovascular events in patients with psoriatic arthritis, psoriasis and rheumatoid arthritis: a population-based cohort study. ann rheum dis. 2015;74(2):326-332. doi:10.1136/annrheumdis-2014-205675 3. nash p, kirkham b, okada m, et al. ixekizumab for the treatment of patients with active psoriatic arthritis and an inadequate response to tumour necrosis factor inhibitors: results from the 24-week randomised, double-blind, placebo-controlled period of the spirit-p2 phase 3 trial. lancet. conclusion skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 828 2017;389(10086):2317-2327. doi:10.1016/s0140-6736(17)31429-0 4. ferreira br, pio-abreu jl, reis jp, figueiredo a. analysis of the prevalence of mental disorders in psoriasis: the relevance of psychiatric assessment in dermatology. psychiatr danub. 2017;29(4):401-406. doi:10.24869/psyd.2017.401 5. yu s, yu cl, huang yc, tu hp, lan cce. risk of developing psoriasis in patients with schizophrenia: a nationwide retrospective cohort study. j eur acad dermatology venereol. 2017;31(9):1497-1504. doi:10.1111/jdv.14303 6. ungprasert p, wijarnpreecha k, cheungpasitporn w. patients with schizophrenia have a higher risk of psoriasis: a systematic review and meta-analysis. psychiatry res. 2018;259:422-426. doi:10.1016/j.psychres.2017.11.021 7. azhar a, zaayman m, silfvast-kaiser a, kivelevitch d, menter a, paek sy. ixekizumab in the treatment of moderate-tosevere plaque psoriasis: patient adherence, satisfaction, and preferences. dermatol ther. 2021;34(1):e14486. doi:10.1111/dth.14486 8. caldarola g, mariani m, pirro f, et al. comparison of shortand long-term effectiveness of ixekizumab and secukinumab in real-world practice. expert opin biol ther. 2021;21(2):279-286. doi:10.1080/14712598.2021.1849133 9. dubovsky an, arvikar s, stern ta, axelrod l. the neuropsychiatric complications of glucocorticoid use: steroid psychosis revisited. psychosomatics. 2012;53(2):103115. doi:10.1016/j.psym.2011.12.007 powerpoint presentation presented at the fall clinical dermatology conference 2022 meeting, october 20–23, 2022, las vegas, nv, usa figure 4. areas patients reported impacting their quality of life figure 3. body areas patients reported most affected by psoriasis 0 20 40 60 80 100 knees arms intertriginous areas legs elbows scalp patients (%) 56% 48% 41% 39% 33% 32% figure 5. most common areas patients reported applying topical treatment other areas include knees (25%), face (23%), groin (22%), armpits (20%), between the buttocks (19%), top of hands (19%), stomach folds (19%), under breasts (17%), and top of feet (17%). figure 6. patient preferences for treatment types figure 2. patient-reported severity of psoriasis symptoms n=507 introduction • plaque psoriasis is a common inflammatory skin condition, affecting about 3% of us adults1 • a survey was conducted by the harris poll in the us, on behalf of arcutis biotherapeutics, to understand the perspectives and burden of patients with psoriasis who use topical treatments to manage their disease • this poster presents the results of this survey related to patient preferences and treatment patterns methods • the 20-minute online survey was conducted from october 21 through november 24, 2021, among 507 us adults diagnosed with psoriasis by a healthcare provider (figure 1) • participants had to use a topical treatment and not use a prescription injectable treatment for their psoriasis • demographic variables included education, age by sex, race/ethnicity, census region, household size, and marital status • a propensity score variable was included to adjust for respondents’ propensity to be online • raked weights were estimated using random iterative method weighting results patient-reported psoriasis symptoms • at the time of diagnosis, most participants (n=507) described their psoriasis symptoms as moderate (59%; figure 2) patient-reported burden of psoriasis • participants estimated that an average of 15% of their bodies was affected by psoriasis – most patients (63%) reported ≤10% of their body was affected – the body areas most often reported to be affected by psoriasis were the scalp, elbows, legs, intertriginous areas, arms, and knees (figure 3) • over 3 in 10 participants said they apply topical treatments to their elbows, scalp, legs, and arms (figure 5) • most (76%) participants preferred topical therapies for psoriasis, while 20% preferred pills and 4% preferred injections (figure 6) • most patients currently using topical treatments agreed to wanting more effective topical treatment options and a single topical therapy that can be used anywhere on the body (figure 8) conclusions • patients with psoriasis want more effective and easier-to-use topical treatment options • while patients with psoriasis have used an average of 2.5 topical treatments, they prefer a single topical therapy that can be used anywhere on the body • most respondents were open to using a new topical treatment for psoriasis and want a product that offers improvement of both plaques and itch april armstrong,1 melodie young,2 melissa seal,3 robert higham,3 teri greiling4 1keck school of medicine, department of dermatology, university of southern california, los angeles, ca, usa; 2mindful dermatology, modern research associates, dallas, tx, usa; 3arcutis biotherapeutics, inc., westlake village, ca, usa; 4department of dermatology, oregon health & science university, portland, or, usa patient perspectives on the prevalence and burden of psoriasis: results from a national survey of adults with psoriasis in the united states mild moderate severe 59% 10% 31% • participants reported psoriasis affecting the scalp, elbows, and legs caused the greatest impact on quality of life (figure 4) 0 20 40 60 80 100 legs arms scalp elbows patients (%) 39% 36% 30% 30% patients’ perspective of psoriasis treatment options • 90% of participants agreed that they wished more effective topical treatment options were available (figure 7) • 25% of participants were dissatisfied with the topical treatments they had used (figure 7) figure 7. patient-reported desire for and satisfaction with topical treatment options figure 8. patient-reported wants from topical psoriasis treatment 0 20 40 60 80 100 instructions for using topical treatments were less confusing topical treatment options were more tolerable topical treatment with fewer safety concerns more topical treatment alternatives to steroids topical treatments were once-daily application use a single topical therapy anywhere on my body more effective topical treatment options patients (%) 53% 78% 80% 81% 87% 90% 90% • nearly all (89%) of participants said they are interested in trying a new topical treatment for psoriasis • the most common product attributes that participants want in a topical psoriasis treatment are improvement of plaques, itch relief, easy to apply, and safe to use (figure 9) figure 9. patient-reported desired attributes of topical psoriasis treatment 0 20 40 60 80 100 ability to use it on all affected areas tolerable for skin safe to use easy to use itch relief improvement in plaques patients (%) 68% 68% 63% 61% 47% 45% 0 20 40 60 80 100 under breasts stomach folds knees top of hands between buttocks arms armpits groin face legs elbows scalp 12% 12% 13% 13% 13% 14% 14% 15% 17% 19% 20% 39% patients (%) figure 1. disposition of patients with psoriasis using topical treatments n=507 sex women: 47% men: 52% mean age 46.3 years mean number of treatment types ever used topical: 2.5 over the counter: 2.1 prescription oral: 0.7 topical pills injections 20% 4% 76% str on gly ag re e so me wh at ag re e so me wh at di sa gr ee str on gly di sa gr ee 0 20 40 60 80 100 54% 37% 8% 2% pa ti en ts (% ) desire for more effective topical treatment options ve ry sa tis fie d so me wh at sa tis fie d so me wh at di ssa tis fie d ve ry dis sa tis fie d 0 20 40 60 80 100 19% 6% 21% 54% pa ti en ts (% ) satisfaction with topical treatment options reference 1. rachakonda td, et al. j am acad dermatol 2014;70:512–516. acknowledgements • this study was supported by arcutis biotherapeutics, inc. • thank you to the investigators and their staff for their participation in the trial • we are grateful to the study participants and their families for their time and commitment • writing support was provided by lauren ramsey, pharmd, alligent biopharm consulting llc, and funded by arcutis biotherapeutics, inc. disclosures aa, my, and tg are investigators and/or consultants for arcutis biotherapeutics, inc. and received grants/research funding and/or honoraria; ms and rh are employees of arcutis biotherapeutics, inc. additional disclosures provided on request. patient perspectives on the prevalence and burden of psoriasis: �results from a national survey of adults with psoriasis in the united states << /ascii85encodepages false /allowtransparency false /autopositionepsfiles true /autorotatepages /none /binding /left /calgrayprofile (dot gain 20%) /calrgbprofile (srgb iec61966-2.1) /calcmykprofile (u.s. web coated \050swop\051 v2) /srgbprofile (srgb iec61966-2.1) /cannotembedfontpolicy /warning /compatibilitylevel 1.3 /compressobjects /off /compresspages false /convertimagestoindexed true /passthroughjpegimages true /createjobticket false /defaultrenderingintent /default /detectblends true /detectcurves 0.0000 /colorconversionstrategy 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() /metadatatitle () /metricpagesize [ 0 0 ] /metricunit /inch /mobilecompatible 0 /namespace [ (adobe) (golive) (8.0) ] /openzoomtohtmlfontsize false /pageorientation /portrait /removebackground false /shrinkcontent true /treatcolorsas /mainmonitorcolors /useembeddedprofiles false /usehtmltitleasmetadata true >> ] >> setdistillerparams << /hwresolution [2400 2400] /pagesize [612.000 792.000] >> setpagedevice presented at the 2022 fall clinical dermatology conference®; october 20-23, 2022; las vegas, nevada background • prurigo nodularis is a chronic inflammatory dermatologic condition characterized by intense pruritus and raised nodular lesions, papules, and/or plaques1 – the global prevalence of pn is estimated to be 730,0002 • pruritus is a severe and often treatment-resistant symptom of pn3 • there are no approved pharmacologic therapies for patients with pn • κand μ-opioid receptors are critical mediators for itch, with important roles in the itch-scratch cycle and pn-related pruritus4 • nalbuphine extended-release (nal er) is a dual-acting κ-opioid receptor agonist/μ-opioid receptor antagonist that acts centrally and peripherally4 – in contrast with activation of µ-opioid receptors, κ-opioid receptor activation is not associated with abuse or addiction5 • the iv formulation of nalbuphine is an unscheduled opioid (ie, not controlled under the controlled substances act by the drug enforcement agency) in the united states and most of europe6,7 • nal er may improve the balance of κand μ-opioid receptor activity and therefore may be an oral treatment option for patients with pn-related pruritus8 objective • to assess the antipruritic and lesion-reducing efficacy and safety of oral nal er in patients with pn in the phase 2b/3 prism trial methods study design • prism (nct03497975) was a randomized, double-blind, placebo-controlled, phase 2b/3 trial of adult patients with confirmed pn, ≥10 pruriginous nodules on ≥2 distinct anatomical areas, and wi-nrs score ≥7 • participants received oral nal er 162 mg or placebo twice daily • the study consisted of a 2-week titration phase, a 12-week fixed-dose treatment phase, and a 2-week off-treatment safety phase • the primary end point was the percentage of responders who had ≥4-point reduction in wi-nrs score • key secondary end points were: – lsm change from baseline in itchyqol – participants with ≥1-category improvement in pas question 5a (to assess improvement in pn skin lesions) oral nalbuphine extended-release is effective in severe prurigo nodularis–associated pruritus: results from a phase 2b/3, double-blind, placebo-controlled study sonja ständer,1 elke weisshaar,2 jennifer l. parish,3 jacek c. szepietowski,4 adam reich,5 neil j. korman,6 enoch bortey,7 thomas r. sciascia7 1münster university hospital, münster, germany; 2ruprecht-karls university, heidelberg, germany; 3thomas jefferson university, philadelphia, pa, usa; 4wroclaw medical university, wroclaw, poland; 5university of rzeszow, rzeszow, poland; 6university hospitals cleveland medical center, cleveland, oh, usa; 7trevi therapeutics, new haven, ct, usa results table 1. participant demographics and baseline disease characteristics nal er n = 168 placebo n = 176 age, mean ± sd, years 59.6 ± 13.3 55.9 ± 14.3 female, n (%) 100 (59.5) 112 (63.6) weight, mean ± sd, kg 85.7 ± 20.5 84.7 ± 20.9 race, n (%) white black or african american native hawaiian or other pacific islander asian multiple 132 (78.6) 24 (14.3) 6 (3.6) 6 (3.6) 0 134 (76.1) 23 (13.1) 11 (6.3) 7 (4.0) 1 (0.6) region, n (%) europe north america 99 (58.9) 69 (41.1) 103 (58.5) 73 (41.5) baseline disease wi-nrs,a mean ± sd itchyqol, mean ± sd no. of prurigo lesions,b n (%) 1-19 20-100 >100 8.6 ± 0.9 84.9 ± 15.7 17 (10.1) 101 (60.1) 50 (29.8) 8.7 ± 0.9 83.9 ± 16.2 22 (12.5) 93 (52.8) 61 (34.7) a for wi-nrs, the baseline value was calculated as the arithmetic mean of the daily wi-nrs values (≥5 measurements required) taken for eligibility review by site at the time of randomization. bstudy participation required ≥10 pruriginous nodules on ≥2 distinct anatomical areas. safety table 2. safety nal er n = 168 placebo n = 176 titration fixed-dose titration fixed-dose participants who had ≥1 teae treatment-related aes 111 (66.1) 86 (51.2) 81 (48.2) 52 (31.0) 55 (31.3) 24 (13.6) 79 (44.9) 22 (12.5) participants who had teaes leading to study discontinuation 33 (19.6) 23 (13.7) 5 (2.8) 7 (4.0) participants who had any saesa 8 (4.8) 6 (3.4) teaes that had >15% incidence in any treatment armb gastrointestinal disorders nausea constipation nervous system disorders dizziness headache 84 (50.0) 51 (30.4) 26 (15.5) 81 (48.2) 51 (30.4) 26 (15.5) 37 (21.0) 16 (9.1) 7 (4.0) 28 (15.9) 5 (2.8) 14 (8.0) ano saes were considered treatment related. bby meddra soc and pt. efficacy figure 1. efficacy of nal er versus placebo in patients with pn nal er 162 mg placebo key secondary end points patients in the nal er group achieved significantly greater lsm change from baseline in itchyqol than those on placebo the proportion of patients in the nal er group achieving ≥1-category improvement from baseline in pruriginous lesions with excoriations/crustb was significantly greater than placebo primary end point the proportion of patients in the nal er group who had ≥4-point improvement from baseline in wi-nrsa score was significantly greater than in the placebo group wi-nrs itchyqol pas 24.7% 13.9% 54.9% 38.0% −16.5 −9.1 70 30 20 p a rt ic ip a nt s w ho h a d ≥ 1c a te g or y im p ro ve m en t, % ( s e) weeks 10 0 0 10 14 40 50 60 45.5 30.3 54.9 38.0 p = 0.0020 p = 0.0064 nal er placebo 0 −5 −10 ls m c ha ng e fr om b a se lin e (s e) weeks −15 −20 0 6 10 14 −10.3 −6.7 −15.5 −7.3 −16.5 −9.1 p = 0.0399 p < 0.0001 p = 0.0002 nal er placebo 35 30 25 r es p on d er s, % ( s e) 20 15 10 5 0 0 6 10 142 5.4 2.0 15.8 3.9 20.9 9.4 24.7 13.9 p = 0.0027 p = 0.0116 p = 0.0157 primary end point p = 0.1352 weeks nal er placebo abased on 7-day wi-nrs scores. bas measured by responses to pas question 5a. summary • the prism study met its primary end point and all key secondary end points – a significantly higher percentage of participants experienced an antipruritic response on week 14 with nal er (24.7%) versus placebo (13.9%) – compared with placebo, nal er treatment also resulted in • greater improvement in itchyqol at weeks 6, 10, and 14 • greater improvement in pruriginous lesions with excoriations/crusts at weeks 10 and 14 • the safety profile of nal er was consistent with its known safety profile – a 36-week open-label study is ongoing to assess the long-term safety and efficacy • use of nal er may provide a novel oral treatment approach references 1. elmariah s et al. j am acad dermatol. 2021;84(3):747-760. 2. prurigo nodularis – market insights, epidemiology, and market forecast. accessed september 14, 2022. https://www.delveinsight.com/report-store/ prurigo-nodularis-market 3. steinke s et al. j am acad dermatol. 2018;79(3):457-463. 4. elmariah s et al. j am acad dermatol. 2021;7:156-163. 5. kim bs et al. abstract presented at: winter clinical dermatology conference–hawaii®; january 16-24, 2021; virtual. 6. drug enforcement administration. nalbuphine hydrochloride. accessed september 14, 2022. https://www.deadiversion.usdoj.gov/drug_chem_ info/nalbuphine.pdf 7. who expert committee on drug dependence. world health organ tech rep ser. 1989;775:1-48. 8. weisshaar e et al. j eur acad dermatol venereol. 2021;36(3):453-461. abbreviations itchyqol, itchy quality of life; iv, intravenous; lsm, least squares mean; meddra, medical dictionary for regulatory activity; nal er, nalbuphine extended release; pas, prurigo activity score; pn, prurigo nodularis; pt, preferred term; sae, serious adverse event; soc, system organ class; sd, standard deviation; se, standard error; teae, treatment-emergent adverse event; wi-nrs, worst itch numerical rating scale acknowledgments medical writing assistance was provided by richard w. davis iv, phd, of apothecom (san francisco, ca) and was funded by trevi therapeutics, inc. (new haven, ct). this study is sponsored by trevi therapeutics, inc. contact information contact the author at sonja.staender@ukmuenster.de for questions or comments. skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 257 short communication the “brownsville bolster”: a novel bolstering technique for full thickness skin grafts saba imani, do1, carlos gomez-meade, do, faad, facms2 1 university of oklahoma, tulsa, ok 2 oklahoma cancer specialists and research institute, tulsa, ok the success of a skin graft is dependent upon several factors including graft vascularization and nutrition absorption. a successful skin graft can be cosmetically appealing as a reconstructive option in certain anatomical sites following surgical treatment with mohs micrographic surgery. to enhance graft survival, bolstering techniques are often used to immobilize the graft and reduce hematoma and seroma formation. commonly used bolstering materials are foam, plastic, cotton balls, and gauze; for suturing, the tie-over technique is most commonly used. 1-4 we present a new method of bolstering skin grafts, the “brownsville bolster”, which has been yielding great results and fast healing in clinical practice for over nine years. this method allows for an even distribution of pressure throughout the skin graft, minimizing risk of pockets that are not vascularized and thus minimizes risk of graft necrosis. after the skin graft is sutured in place (figure 1b), we apply a thin layer of sterile hydroactive paste and cover the grafted skin with petrolatum blend fine mesh gauze. this dressing is occlusive, maintains a moist environment, is non-adherent and non-traumatic to the wound, and is easily cut and molded to the graft size. then, a hydrocolloid dressing, a formulation that creates a vapor-permeable outer film and provides an occlusive moist environment, is applied on top of the petrolatum dressing gauze. it is sutured in place using a domelike distribution of pressure on the skin graft, approximately 1 cm away from the graft edge, so as to not traumatize the skin graft (figure 1c). three opposite-ended interrupted sutures are placed to anchor the bolster. a running epidermal suture is used to secure the hydrocolloid dressing in place. additionally, 2-3 opposite ended interrupted sutures can be used. additive hydrocolloid dressing is associated with shorter treatment times and fewer complications 5. the “brownsville bolster” technique incorporates the sterile hydroactive paste followed by the petrolatum blend fine mesh gauze, which is then sealed with the hydrocolloid dressing anchored in place using a running epidermal suture. this method allows for an even distribution of pressure to be applied to the skin graft and decreases shearing forces across the graft. furthermore, it provides a waterproof barrier over the dressing as well as mechanical and thermal protection. the honeycomb matrix of hydrocolloid particles absorbs exudate to form a soft, moist gel; this helps with relieving discomfort. 6 skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 258 figure 1. this dressing can be worn continuously for approximately 7 days, after which it is removed and wound care to the skin graft can be continued until healed. we advise patients to keep the bolster dry for 7 days, if possible, to ensure that the bolster remains firmly in place and is not overly moist or macerated. the authors found that the use of this bolster method is highly effective in providing high graft viability, providing adequate pressure onto the graft bed and skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 259 therefore increasing graft vascularization and viability (figure 1d). in addition, we found that this bolstering method is more stable and cosmetically pleasing when compared to traditional petrolatum dressing gauze-only bolsters. conflict of interest disclosures: none funding: none corresponding author: saba imani, do 4444 e 41st st tulsa, ok 74135 email: saba-imani@ouhsc.edu references: 1. egan, c.a. and j.w. gerwels, surgical pearl: use of a sponge bolster instead of a tie-over bolster as a less invasive method of securing full-thickness skin grafts. j am acad dermatol, 1998. 39(6): p. 1000-1. 2. srivastava, d. and d.j. kouba, a "lilliputian" technique for rapid and efficient securing of bolster dressings over full-thickness skin grafts. dermatol surg, 2009. 35(8): p. 12801. 3. wells, m.d. and d.s. kirn, a new method of skin-graft stabilization: the reston technique. ann plast surg, 1995. 34(5): p. 554-6. 4. kromka, w., m. cameron, and r. fathi, tieover bolster dressings vs basting sutures for the closure of full-thickness skin grafts: a review of the literature. j cutan med surg, 2018. 22(6): p. 602-606. 5. jeong, h.s., k.s. kim, and h.k. lee, hydrocolloid dressings in skin grafting for immobilization and compression. dermatol surg, 2011. 37(3): p. 320-4. 6. day, a., et al., managing sacral pressure ulcers with hydrocolloid dressings: results of a controlled, clinical study. ostomy wound manage, 1995. 41(2): p. 52-4, 56, 58 passim. mailto:saba-imani@ouhsc.edu powerpoint presentation impact of prior treatment in the efficacy and tolerability of tirbanibulin ointment 1% for actinic keratosis: pooled results from two phase 3 studies methods • in the phase 3 trials, patients with 4-8 clinically visible ak lesions in a 25 cm2 area were randomized 1:1 to tirbanibulin ointment 1% or vehicle (once-daily, 5 consecutive days, self-application). the study design is shown in figure 1. synopsis • tirbanibulin was evaluated as a field treatment for actinic keratosis (ak) of face or scalp in two phase 3, randomized, double-blind, vehicle-controlled studies (nct03285477, nct03285490)1. • pooled data showed complete (100%) clearance (cc) and partial (≥75%) clearance (pc) rates of 49% and 72% for tirbanibulin-treated versus 9% and 18% for vehicletreated participants, respectively • local skin reactions (lsr) were mostly mild-to-moderate, the mean±standard deviation (sd) maximum lsr severity composite score being 4.4±2.2 for tirbanibulin-treated and 1.6±1.4 for vehicle-treated participants. • compared to pooled phase 3 trials, in this post-hoc analysis the efficacy of tirbanibulin in pretreated areas was similar, and there were no differences in tolerability in terms of lsr. • although sample sizes were limited and statistical significance was not tested, results show that tirbanibulin has a favorable safety/efficacy profile to be used either as first-line or after other treatments, and warrant further research on the most suitable treatment sequence in individuals with ak. conclusions • count of clinically visible ak lesions (lesion count) was performed for all patients at different time points. • in each of the safety evaluations performed from baseline to d57, lsr (i.e., erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, erosions/ulceration) were graded 0-3 (absent-severe). an lsr composite score (sum of scores) was calculated for each participant visit (range 0-18), and maximum composite scores were averaged for the study period. • for the current analysis, participants were considered pretreated if receiving prior treatment in the same area as tirbanibulin/vehicle. 2021 fall clinical dermatology conference for pas & nps figure 1. design of phase 3 studies • median (minimum-maximum) time since previous treatment was available in a subset of patients, being 23.7 (1.0-157.8) and 22.7 (0.2-157.8) months in cryosurgery-pretreated and topical-pretreated participants receiving tirbanibulin, respectively (table 2). • tirbanibulin treatment resulted in cc in 45.1% of cryosurgery-pretreated and in 33.3% of topical-pretreated participants (figure 2). • moreover, pc was achieved by 71.4% of cryosurgery-pretreated and by 60.0% of topicalpretreated participants receiving tirbanibulin (figure 2). • maximum mean lsr composite scores were similar between pretreated and non-pretreated participants in both tirbanibulin and vehicle groups; and between cryosurgeryand topicalpretreated participants in the tirbanibulin and vehicle groups (table 3). table 1. baseline characteristics ak, actinic keratosis; bmi, body mass index; max; maximum; min, minimum; sd, standard deviation. tirbaninulin (n=353) vehicle (n=349) pretreated (n=130) non-pretreated (n=223) pretreated (n=141) non-pretreated (n=208) age (years), mean (sd) 69.8 (9.1) 69.1 (8.3) 70.7 (9.1) 69.9 (9.1) male, n (%) 112 (86.2) 193 (86.5) 124 (87.9) 180 (86.5) bmi (kg/m2), mean (sd) 28.4 (4.9) 29.1 (5.2) 28.7 (4.9) 28.1 (4.6) fitzpatrick skin type, n (%) type i 10 (7.7) 39 (17.5) 13 (9.2) 25 (12.0) type ii 80 (61.5) 120 (53.8) 94 (66.7) 130 (62.5) type iii 35 (26.9) 53 (23.8) 31 (22.0) 48 (23.1) type iv-vi 5 (3.8) 11 (4.9) 3 (2.1) 5 (2.4) ak lesion count, median (min-max) 6.0 (4.0-8.0) 6.0 (4.0-8.0) 6.0 (4.0-8.0) 6.0 (4.0, 8.0) objective • this post-hoc analysis of the pooled phase 3 data assessed efficacy and tolerability according to prior ak treatment in the treatment area. todd schlesinger1, neal bhatia2, brian berman3, ayman grada4, laura padullés5, francisco hernández6, david cutler7, mark lebwohl8 1 clinical research center of the carolinas, charleston, sc, usa; 2 therapeutics clinical research, san diego, ca, usa; 3 department of dermatology and cutaneous surgery, university of miami miller school of medicine, florida, usa; 4 almirall, malvern, pa, usa; 5 almirall, barcelona, spain; 6 almirall, sant feliu de llobregat, spain; 7 athenex, inc., buffalo, ny, usa; 8 icahn school of medicine at mount sinai, new york, ny, usa table 3. highest mean lsr composite score from baseline to d57 population tirbanibulin vehicle overall pretreated (t=130/v=141) 4.1 ± 2.0 1.7 ± 1.5 cryosurgery-pretreated (t=91/v=114) 4.1 ± 1.9 1.8 ± 1.5 topical-pretreated (t=45/v=39) 3.9 ± 1.8 1.8 ± 1.9 non-pretreated (t=223/v=208) 4.6 ± 2.3 1.5 ± 1.4 mean ± standard deviation. twenty-two patients had prior treatment with cryosurgery and topicals. these are included in both cryosurgeryand topical-pretreated categories. d, day; lsr, local skin reactions; t, tirbanibulin; v, vehicle. figure 2. complete and partial clearance rates of ak lesions at d57 • phase iii studies were funded by athenex. post-hoc analysis/medical writing was funded by almirall. • w riting support was provided by tfs healthscience. acknowledgements ts has served as a consultant/speaker with honorarium, advisor and/or investigator for almirall, biofrontera, galderma, leo, ortho and sun pharmaceuticals; nb has served as a consultant with honorarium and investigator for almirall, biofrontera, leo, ortho, and sunpharma; bb has served as a consultant, speaker, and/or investigator for almirall, biofrontera, leo and pierre-fabre, and also participated in the us biofrontera pdt advisory council; ag, lp and fh are employees of almirall; dc is an employee of athenex; ml is an employee of mount sinai and receives research funds from: abbvie, amgen, arcutis, avotres, boehringer ingelheim, dermavant sciences, eli lilly, incyte, janssen research & development, llc, ortho dermatologics, regeneron, and ucb, inc., and is a consultant for aditum bio, almirall, altrubio inc., anaptysbio, arcutis, inc., aristea therapeutics, arrive technologies, avotres therapeutics, biomx, boehringer-ingelheim, bristol-myers squibb, cara therapeutics, castle biosciences, corrona, dermavant sciences, dr. reddy’s laboratories, evelo biosciences, evommune, inc., facilitatation of international dermatology education, forte biosciences, foundation for research and education in dermatology, helsinn therapeutics, hexima ltd., leo pharma, meiji seika pharma, mindera, pfizer, seanergy, and verrica. conflicts of interest 1) blauvelt a et al. new engl j med 2021;384:512-20. references • pretreated participants were 130/353 (37%) of those randomized to tirbanibulin and 141/349 (40%) of those randomized to vehicle. • of tirbanibulin-pretreated participants, 91/130 (70%) had received cryosurgery and 45/130 (35%) topicals in the same treatment area (22 in each group had received both). • there were no major differences in the baseline characteristics between pretreated and nonpretreated participants. baseline characteristics are shown in table 1. results ak, actinic keratosis; d, day. table 2. time (months) since previous treatment no complete clearance complete clearance overall cryosurgery-pretreated n 26 23 49 mean (sd) 31.4 (32.6) 24.2 (21.7) 28.0 (28.0) median (min-max) 26.7 (1.9-157.8) 20.7 (1.0-65.5) 23.7 (1.0-157.8) topical-pretreated n 12 7 19 mean (sd) 33.0 (41.4) 14.0 (12.7) 26.0 (34.5) median (min-max) 25.0 (2.3-157.8) 14.6 (0.2-35.2) 22.7 (0.2-157.8) time since previous treatment was only available in a subset of patients. max, maximum; min, minimum; sd, standard deviation. day 57 1 year day 57 1 year tirbanibulin once daily for 5 days n=175 351 patients per trial vehicle once daily for 5 days n=176 1-year follow-up phase (only for patients with complete clearance at day 57) 57-day phase day 29day 15day 8 day 29day 15day 8 safety and efficacy assessed at all time points primary efficacy endpoint: % patients with complete clearance at day 57 treatment period response assessment period skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 157 brief article sars-cov-2 infection uncovering latent mycobacterium leprae infection christopher mancuso, do, mhs1, paloma reiter, do1, regina zambrano, do2, ritu saini, md1, suzanne sirota-rozenberg, do1 1 st. john’s episcopal hospital, department of dermatology, far rockaway, new york 2 st. john’s episcopal hospital, department of family medicine, far rockaway, new york as the number of coronavirus disease 2019 (covid-19) cases rise globally, more information is being brought to light regarding the relationship between covid19 and leprosy. there are very few reports of leprosy with concurrent covid-19.1 limited literature suggests two theories have been postulated thus far: (1) covid-19 infection may trigger a leprosy reaction; and (2) leprosy treatment may cause patients to experience a severe manifestation of covid-19 infection.1,2 also known as hansen’s disease, leprosy is a chronic granulomatous infection caused by the bacteria mycobacterium leprae that spreads via respiratory droplets.3 leprosy involves immune factors, such as interleukins (il) 4, 5, 6, 10, 13, that covid19 may activate or exacerbate.4,5 in addition, infections and stress are thought to be triggers for leprosy reactions.6 while early diagnosis and treatment with antibiotics and anti-inflammatory medications can cure an individual with leprosy, it may create susceptibility to covid-19 by changing a patient’s cytokine profile.1,5,7,8 despite the current social distancing mandates to prevent acquisition of covid-19, many patients with leprosy are a part of lower socioeconomic groups associated with overcrowded living and poor sanitary conditions.1,3 combined with the historical shame and discrimination that leprosy patients experience, this creates major vulnerability in this patient population.1,3,6 we present a case of newly diagnosed leprosy post-covid-19 infection in a middleaged male. to our knowledge, this is the first reported case of its kind in the united states. abstract leprosy is a chronic granulomatous infection caused by the bacteria mycobacterium leprae. it can remain dormant in a patient without any symptoms until triggered by a stressor on the body. during the coronavirus disease 2019 (covid-19) pandemic, a significant amount of emotional and psychological stress was endured by patients. in addition, many patients experienced exacerbations of their preexisting conditions. few reports have described cases of leprosy with concurrent covid19. this brief article presents a case of newly diagnosed leprosy in a middle-aged male following a covid-19 infection. to our knowledge, this is the first reported case of its kind in the united states. introduction case report skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 158 a 46-year-old fitzpatrick vi, africanamerican man with a significant past medical history of recent covid-19 infection in april 2020 presented to the dermatology clinic on july 2, 2020 with a three-week history of a rash on his face. the patient reported that he migrated from guyana three years ago and did not have a history of or exposure to leprosy. of note, the patient did admit to an increased amount of stress amidst the covid-19 pandemic. on physical examination, the patient had multiple edematous and erythematous plaques of his forehead, periocular areas, nose, malar cheeks, and temples; forming the classical leonine facies (figure 1). patient admitted to hyperesthesia of the upper extremities without pruritus. a 3mm punch biopsy was performed on a plaque of the patient’s left upper cheek. the biopsy was reported as multibacillary leprosy with innumerable beaded or fragmented organisms (figure 2). the patient was started on clofazimine 50mg daily and rifampin 600mg daily, and sent for glucose6-phosphate dehydrogenase (g6pd) deficiency testing before starting dapsone 100mg daily. infectious disease was consulted for further management and the health department was notified. covid-19 is a viral respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (sars-cov-2) that emerged in wuhan, china in december 2019. the spectrum of disease caused by covid-19 ranges from asymptomatic to sars.7 as the number of cases increase worldwide, clinicians realize that patients with covid-19 may experience various coinfections. presently, knowledge regarding co-infection with leprosy is sparse, but a few theories have been proposed. leprosy is a chronic granulomatous infection that leads to various cutaneous manifestations.3,5 type 1 leprosy, the tuberculoid form, is a type iv hypersensitivity reaction with a th1 cell mediated response.3,4,5 this form is characterized by an intense tnf-α and ifnγ reaction, leading to decreased m. leprae bacilli and less cutaneous manifestations.3,4,5 type 2 leprosy, the lepromatous form, is a type iii hypersensitivity reaction with a th2 helper t-cell response.3,4,5 this form demonstrates impaired immunity due to il-4, il-10, and tgf-β secretion, causing large numbers of bacilli and destruction of peripheral nerves, skin, mucosa, and bones.3,4,5 type 2 reactions, which include erythema nodosum leprosum, are associated with immune complex deposition and neutrophil infiltrate.3 it has been suggested that microbial infections and stress are triggers for leprosy reactions. the literature has shown sarscov-2 to influence neutrophil infiltration, eventually creating hyperinflammation or cytokine storm syndrome in a number of covid-19 cases.2,4,9,10 limited studies proposed two theories to explain the relationship between leprosy and covid-19. discussion skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 159 figure 1. a) cushion-like centrofacial infiltrates (leonine facies) of the forehead, loss of eyebrows and eyelashes, distortion of the nose b) leonine facies with thickening of the temple, and characteristic infiltration of the auricle figure 2. a) hematoxylin-eosin stain section of biopsy demonstrating nodular mononucleated histiocytes with numerous admixed lymphocytes and a grenz zone within the papillary dermis (100x magnification). b) fite stain section of biopsy notable for numerous beaded or fragmented acid-fast bacilli with a perivascular lymphohistiocytic infiltrate and globi (400x magnification) a. a. b. b. skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 160 the first theory states that covid-19 is a risk factor for triggering a leprosy reaction due to its effect on various immunologic events. type 1 leprosy involves multiple cytokines, therefore covid-19 infection may trigger a type 1 leprosy reaction due to its ability to induce secretion of similar cytokines. type 2 leprosy is known to be associated with dermal neutrophil infiltrate, leading to skin disfiguration. sars-cov-2 also induces extensive neutrophil infiltrate, specifically in the pulmonary capillaries, that eventually enters circulation.1,9,10 increased circulating neutrophils influenced by sarscov-2 may potentiate or exacerbate a type 2 leprosy infection, as well as hasten or worsen clinical course.2 overall, this first theory suggests that covid-19 may trigger lepromatous reactions. the second theory proposes that leprosy patients undergoing active treatment with anti-inflammatory medications are at an increased risk of acquiring severe manifestations of covid-19.1,7 specifically, type 1 leprosy is treated with prednisone, and type 2 leprosy is treated with thalidomide.1,5 both drugs interfere with the host’s inflammatory response and create a dose-dependent immunosuppressed state.8 there is concern that patients being treated for leprosy are vulnerable to a severe clinical manifestation of covid-19, such as sars.1,7,8 there is also conflicting literature that suggests immunosuppressed patients may instead be protected.7 currently, more large-scale studies must be done to state with confidence how immunosuppressives impact the acquisition and clinical course of covid-19. although this theory does not relate to our case directly, it is an important consideration for the management of leprosy patients during the pandemic. leprosy reactions may be triggered by stress and infections, and the covid-19 pandemic has caused significant emotional and psychological stress on patients.6 when considering this and the two theories proposed, our unique case suggests that covid-19 may induce or exacerbate leprosy reactions.4 leprosy reactions may lead to disfiguring complications and social isolation in a vulnerable patient population, therefore early diagnosis and treatment is necessary to minimize detrimental complications.6 throughout the pandemic, dermatologists must increase their index of suspicion for uncommon cases due to the possibility of covid-19 triggers. acknowledgements: we would like to thank shane a. meehan, md, director of dermatopathology at nyu langone health for his assistance with this case and for the histologic photographs. conflict of interest disclosures: none funding: none corresponding author: christopher mancuso 190 beach 69th street, apt 2e arverne, ny 11692 email: cjmancuso@gmail.com references: 1. rathod s, suneetha s, narang t, et al. management of leprosy in the context of covid-19 pandemic: recommendations by sig leprosy (iadvl academy). indian dermatol online j. 2020;11(3):345-348. published 2020 may 10. doi:10.4103/idoj.idoj_234_20 2. schmitz v, dos santos jb. covid-19, leprosy, and neutrophils. plos negl trop dis. 2021;15(1):e0009019. published 2021 jan 7. doi:10.1371/journal.pntd.0009019itz conclusion skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 161 3. antunes de, goulart imb, goulart lr. will cases of leprosy reaction increase with covid-19 infection? plos negl trop dis. 2020;14:e0008460 10.1371/journal.pntd.0008460 4. santos vs, quintans-júnior lj, barboza ws, araújo aas, martins-filho pr. clinical characteristics and outcomes in patients with covid-19 and leprosy [published online ahead of print, 2020 a 5. nery ja, bernardes filho f, quintanilha j, machado am, oliveira sde s, sales am. understanding the type 1 reactional state for early diagnosis and treatment: a way to avoid disability in leprosy. an bras dermatol. 2013;88(5):787-792. doi:10.1590/abd18064841.20132004 6. bilik l, demir b, cicek, d. leprosy reactions. hansen's disease the forgotten and neglected disease. 2019. doi: 10.5772/intechopen.72481 7. thng zx, de smet md, lee cs, et al. covid-19 and immunosuppression: a review of current clinical experiences and implications for ophthalmology patients taking immunosuppressive drugs [published online ahead of print, 2020 jun 12]. br j ophthalmol. 2020;bjophthalmol-2020-316586. doi:10.1136/bjophthalmol-2020-316586 8. liu d, ahmet a, ward l, et al. a practical guide to the monitoring and management of the complications of systemic corticosteroid therapy. allergy asthma clin immunol. 2013;9(1):30. published 2013 aug 15. doi:10.1186/1710-14929-30 9. barnes bj, adrover jm, baxter-stoltzfus a, et al. targeting potential drivers of covid-19: neutrophil extracellular traps. j exp med. 2020;217(6):e20200652. doi:10.1084/jem.20200652 10. mehta p, mcauley df, brown m, et al. covid19: consider cytokine storm syndromes and immunosuppression. lancet. 2020;395(10229):1033-1034. doi:10.1016/s0140-6736(20)30628-0 deucravacitinib, an oral, selective tyrosine kinase 2 (tyk2) inhibitor, in moderate to severe plaque psoriasis: 52-week efficacy results from the phase 3 poetyk pso-1 and pso-2 trials richard b warren,1 april w armstrong,2 melinda gooderham,3 bruce strober,4 diamant thaçi,5 shinichi imafuku,6 howard sofen,7 lynda spelman,8 neil j korman,9 min zheng,10 elizabeth colston,11 john throup,11 sudeep kundu,11 renata m kisa,11 subhashis banerjee,11 andrew blauvelt12 1dermatology centre, salford royal nhs foundation trust, manchester nihr biomedical research centre, the university of manchester, manchester, uk; 2university of southern california, los angeles, ca, usa; 3skin center for dermatology, queen’s university, and probity medical research, peterborough, on, canada; 4yale university, new haven, ct, and central connecticut dermatology research, cromwell, ct, usa; 5university of lübeck, lübeck, germany; 6fukuoka university hospital, fukuoka, japan; 7ucla school of medicine, los angeles, ca, usa; 8veracity clinical research, woolloongabba, qld, australia; 9case western reserve university and university hospitals, cleveland, oh, usa; 10second affiliated hospital, zhejiang university school of medicine, national key clinical department of dermatology, hangzhou, zhejiang province, china; 11bristol myers squibb, princeton, nj, usa; 12oregon medical research center, portland, or, usa presented at the 2022 winter clinical dermatology conference — hawaii® (wc22); january 14−19, 2022; kauai, hi, and virtual this is an encore of the 2021 eadv 30th congress presentation this poster may not be reproduced without written permission from the authors.email for richard b warren, md, phd: richard.warren@manchester.ac.uk introduction • tyrosine kinase 2 (tyk2) is an intracellular enzyme that mediates signaling of cytokines (interleukin [il]-23, il-12, and type i interferons) involved in psoriasis pathogenesis1 • deucravacitinib is an oral agent that selectively inhibits tyk2 via an allosteric mechanism by uniquely binding to the regulatory domain rather than to the more conserved active domain where janus kinase (jak) 1/2/3 inhibitors bind (figure 1)1 — ≥100-fold greater selectivity for tyk2 vs jak 1/3 and ≥2000-fold greater selectivity for tyk2 vs jak 2 in cells1,2 • in the phase 3 poetyk pso-1 and pso-2 trials, deucravacitinib was significantly more efficacious than placebo and apremilast based on the coprimary endpoints of ≥75% reduction from baseline in psoriasis area and severity index (pasi 75) and static physician’s global assessment (spga) score of 0/1 at week 16 and was well tolerated in patients with moderate to severe plaque psoriasis3 figure 1. mechanism of action of deucravacitinib deucravacitinib (allosteric inhibitor) regulatory domain catalytic domain atp-binding active site (other kinase inhibitors) tyk2 atp, adenosine triphosphate; tyk2, tyrosine kinase 2. objective • to evaluate the efficacy of deucravacitinib over 52 weeks in poetyk pso-1 and pso-2, including: — efficacy of continuous deucravacitinib treatment and switching from placebo to deucravacitinib at week 16 through week 52 (pso-1) — maintenance of efficacy on continued treatment and durability of response through week 52 after treatment withdrawal among week 24 pasi 75 responders (pso-2) methods key design elements • the poetyk pso-1 and pso-2 study designs are shown in figure 2 • key eligibility criteria — adults with moderate to severe plaque psoriasis — pasi ≥12, spga ≥3, body surface area (bsa) ≥10% — stratified by geographic region, body weight, and prior biologic use • coprimary endpoints were the proportion of patients who achieved pasi 75 and spga 0/1 responses vs placebo at week 16 figure 2. study designs poetyk pso-1 (n = 666) poetyk pso-2 (n = 1020) deucravacitinib 6 mg qdplacebo (n = 166) deucravacitinib 6 mg qd<pasi 50 apremilast 30 mg bid≥pasi 50 titrate* 1 :2 :1 r an d om iz at io n weeks 16 24 520 deucravacitinib 6 mg qdplacebo (n = 255) deucravacitinib 6 mg qd (n = 511) deucravacitinib 6 mg qd<pasi 75 deucravacitinib 6 mg qd<pasi 75 deucravacitinib 6 mg qd deucravacitinib 6 mg qd placebob ≥pasi 75 apremilast 30 mg bida (n = 254) ≥pasi 75 1 :2 :1 r an d om iz at io n weeks 16 24 520 1:1 deucravacitinib 6 mg qdplacebob deucravacitinib 6 mg qd (n = 332) primary endpoint primary endpoint apremilast 30 mg bida (n = 168) aapremilast was titrated from 10 mg qd to 30 mg bid over the first 5 days of dosing. bupon relapse (≥50% loss of week 24 pasi percentage improvement from baseline), patients were to be switched to deucravacitinib 6 mg qd. bid, twice daily; pasi 50, ≥50% reduction from baseline in psoriasis area and severity index; pasi 75, ≥75% reduction from baseline in pasi; qd, once daily. outcome measures • pso-1 — efficacy of continuous deucravacitinib treatment through week 52 • pasi 75, pasi 90, pasi 100 • spga 0/1, spga 0 — efficacy of switching from placebo to deucravacitinib treatment at week 16 through week 52 • pasi 75 and spga 0/1 • percentage change from baseline in pasi • scalp-specific physician’s global assessment (ss-pga) score of 0/1 (clear/almost clear scalp psoriasis) • dermatology life quality index (dlqi) score of 0/1 • pso-2 — maintenance of deucravacitinib response from week 24 to week 52 among week 24 pasi 75 responders • pasi 75 • spga 0/1 — time to loss of pasi 75 response after deucravacitinib withdrawal among week 24 pasi 75 responders results baseline patient demographics and disease characteristics • baseline patient demographics and disease characteristics were largely similar across treatment groups in pooled data from the 2 trials (table 1) table 1. baseline patient demographics and disease characteristics poetyk pso-1 poetyk pso-2 placebo (n = 166) deucravacitinib (n = 332) apremilast (n = 168) placebo (n = 255) deucravacitinib (n = 511) apremilast (n = 254) age, y, mean (sd) 47.9 (14.0) 45.9 (13.7) 44.7 (12.1) 47.3 (13.6) 46.9 (13.4) 46.4 (13.3) weight, kg, mean (sd) 89.1 (22.3) 87.9 (21.8) 87.5 (21.1) 91.5 (20.2) 92.3 (21.9) 93.5 (22.2) female, n (%) 53 (31.9) 102 (30.7) 58 (34.5) 74 (29.0) 175 (34.2) 97 (38.2) race, n (%) white 128 (77.1) 267 (80.4) 139 (82.7) 232 (91.0) 474 (92.8) 229 (90.2) asian 34 (20.5) 59 (17.8) 28 (16.7) 8 (3.1) 24 (4.7) 12 (4.7) other 4 (2.4) 6 (1.8) 1 (0.6) 15 (5.9) 13 (2.5) 13 (5.1) disease duration, y, mean (sd) 17.3 (12.8) 17.1 (12.4) 17.7 (11.8) 19.9 (12.8) 19.6 (12.9) 18.9 (12.4) prior systemic treatment use, n (%) biologic 63 (38.0) 130 (39.2) 66 (39.3) 83 (32.5) 165 (32.3) 79 (31.1) no prior systemic therapy 57 (34.3) 132 (39.8) 59 (35.1) 116 (45.5) 237 (46.4) 114 (44.9) spga, n (%) 3 = moderate 128 (77.1) 257 (77.4) 139 (82.7) 217 (85.1) 408 (79.8) 196 (77.2) 4 = severe 37 (22.3) 75 (22.6) 29 (17.3) 38 (14.9) 103 (20.2) 58 (22.8) pasi, mean (sd) 20.7 (8.0) 21.8 (8.6) 21.4 (9.0) 21.1 (9.0) 20.7 (7.5) 21.6 (8.4) dlqi, mean (sd) 11.4 (6.6) 12.0 (6.7) 12.4 (6.8) 11.8 (6.8) 11.8 (6.5) 12.5 (6.7) bsa, %, mean (sd) 25.3 (16.9) 26.6 (15.9) 26.6 (16.1) 25.3 (15.7) 26.3 (15.8) 28.3 (16.5) pssd symptom score, mean (sd) 51.4 (26.8) 51.7 (25.2) 56.2 (25.2) 50.1 (24.8) 52.3 (26.3) 51.9 (25.4) bsa, body surface area; dlqi, dermatology life quality index; pasi, psoriasis area and severity index; pssd, psoriasis symptoms and signs diary; spga, static physician’s global assessment. poetyk pso-1 and pso-2 patient disposition over 52 weeks • the patient disposition for both trials over 52 weeks is listed in table 2 table 2. disposition of patients over 52 weeks patients, n treatment week 0 week 16 week 24 week 52 poetyk pso-1 continuous deucravacitinib (week 0−52) 332 307 302 268 placebo (week 0−16) − deucravacitinib (week 16−52) 165 145 140 129 poetyk pso-2 deucravacitinib (week 0−16) 510 456b week 24 pasi 75 responders − rerandomized to deucravacitinib (week 24−52)a 148 138 week 24 pasi 75 responders − rerandomized to placebo (week 24−52)a 150 133 a142 patients did not achieve pasi 75 response at week 24 and continued to receive deucravacitinib treatment until week 52. ban additional 16 patients discontinued deucravacitinib treatment between weeks 16 and 24. pasi 75, ≥75% reduction from baseline in psoriasis area and severity index. poetyk pso-1 pasi and spga responses • pasi 75 and spga 0/1 responses were maintained from week 16 to week 52 in patients who received continuous deucravacitinib treatment (figure 3) • pasi 90, pasi 100, and spga 0 responses (secondary efficacy endpoints) were also maintained through 52 weeks in patients treated with deucravacitinib figure 3. poetyk pso-1: pasi and spga responses with deucravacitinib through week 52 (nri) 0 10 20 30 40 50 60 70 80 90 100 0 4 8 12 16 20 24 28 32 36 40 44 48 52 r e sp o n se r at e , % weeks 12 65.1% 44.0% 19.3% 58.4% 35.5% 14.2% pasi 75 pasi 90 pasi 100 0 10 20 30 40 50 60 70 80 90 100 0 4 8 12 16 20 24 28 32 36 40 44 48 52 r e sp o n se r at e , % weeks 53.6% 17.5% 12 spga 0/1 spga 0 52.7% 23.5% primary endpoint primary endpoint pasi 75 (n = 332) spga 0/1a (n = 332) nri was used to impute missing data. aspga response is defined as a score of 0 or 1, with ≥2-point improvement from baseline. nri, nonresponder imputation; pasi, psoriasis area and severity index; pasi 75, ≥75% reduction from baseline in pasi; pasi 90, ≥90% reduction from baseline in pasi; pasi 100, 100% reduction from baseline in pasi; spga 0/1, static physician’s global assessment score of 0 or 1. • patients who switched from placebo to deucravacitinib at week 16 demonstrated pasi 75 and spga 0/1 responses at week 52 comparable to those observed in patients who received continuous deucravacitinib treatment from day 1 (figure 4) figure 4. poetyk pso-1: pasi 75 and spga 0/1 responses through week 52 in patients randomized to deucravacitinib and placebo (nri) 0 10 20 30 40 50 60 70 80 90 100 0 4 8 12 16 20 24 28 32 36 40 44 48 52 0 10 20 30 40 50 60 70 80 90 100 0 4 8 12 16 20 24 28 32 36 40 44 48 52 58.4%* 12.7% 68.3% primary endpoint pasi 75 weeks r e sp o n se r at e , % 1 2 weeks spga 0/1a primary endpoint r e sp o n se r at e , % 53.6%* 7.2% 12 53.8% 52.7% 65.1% deucravacitinib (n = 332) placebo (n = 166) placebo-deucravacitinib (n = 145) nri was used to impute missing data. aspga response is defined as a score of 0 or 1, with ≥2-point improvement from baseline. *p < 0.0001 vs placebo. nri, nonresponder imputation; pasi 75, ≥75% reduction from baseline in psoriasis area and severity index; spga 0/1, static physician’s global assessment score of 0 or 1. • patients who switched from placebo to deucravacitinib at week 16 demonstrated percentage changes from baseline in pasi at week 52 comparable to those observed in patients who received continuous deucravacitinib treatment from day 1 (figure 5) figure 5. poetyk pso-1: percentage change from baseline in pasi through week 52 in patients randomized to deucravacitinib and placebo (mbocf) deucravacitinib (n = 332) placebo (n = 166) baseline pasi, mean (sd) 21.8 (8.6) 20.7 (8.0) -100 -90 -80 -70 -60 -50 -40 -30 -20 -10 0 0 4 8 12 16 20 24 28 32 36 40 44 48 52 m e an p e rc e n ta ge ch an ge f ro m b as e li n e p a si weeks -80.5% -24.3% -71.6% 1 2 -78.4% primary endpoint deucravacitinib (n = 332) placebo (n = 166) placebo-deucravacitinib (n = 145) mbocf was used to impute missing data. mbocf, modified baseline observation carried forward; pasi, psoriasis area and severity index. poetyk pso-1 ss-pga 0/1 through week 52 • ss-pga 0/1 responses at week 16 were maintained through week 52 with continuous deucravacitinib treatment (figure 6) — patients who switched from placebo to deucravacitinib at week 16 achieved comparable ss-pga 0/1 responses at week 52 to those who received continuous deucravacitinib treatment figure 6. poetyk pso-1: scalp psoriasis − ss-pga 0/1 through week 52 (nri) 0 10 20 30 40 50 60 70 80 90 100 0 4 8 12 16 20 24 28 32 36 40 44 48 52 r e sp o n se r at e , % weeks 70.3% 17.4% 65.6% 69.7% primary endpoint deucravacitinib (n = 209) placebo (n = 121) placebo-deucravacitinib (n = 109) 1 2 nri was used to impute missing data. the majority (88.9%) of patients had scalp involvement at baseline; >55% of patients had moderate to severe scalp psoriasis (ss-pga ≥3) at baseline and were evaluated for ss-pga 0/1 responses.4 nri, nonresponder imputation; qd, once daily; ss-pga 0/1, scalp-specific physician’s global assessment score of 0 or 1. • patients who switched from placebo to deucravacitinib at week 16 achieved dlqi 0/1 responses at week 52 comparable to those observed in patients who received continuous deucravacitinib treatment from day 1 (figure 7) figure 7. poetyk pso-1: dlqi 0/1 response through week 52 in patients randomized to deucravacitinib and placebo (nri) deucravacitinib (n = 332) placebo (n = 166) baseline dlqi, mean (sd) 12.0 (6.7) 11.4 (6.6) weeks 0 10 20 30 40 50 60 70 80 90 100 0 4 8 12 16 20 24 28 32 36 40 44 48 52 43.2% 46.1% 1 2 r e sp o n se r at e , % 41.0% 10.6% primary endpoint deucravacitinib (n = 332) placebo (n = 166) placebo-deucravacitinib (n = 141) nri was used to impute missing data. dlqi score of 0 or 1 among patients with a baseline score of 2. dlqi 0/1 is indicative of no impact on a patient’s life. dlqi 0/1, dermatology life quality index score of 0 or 1; nri, nonresponder imputation. • pasi 75 and spga 0/1 responses were maintained on continuous treatment through week 52 in the majority of deucravacitinib-treated patients who achieved pasi 75 at week 24 (figure 8) • median time to loss of pasi 75 response was 12 weeks in the randomized withdrawal arm figure 8. poetyk pso-2: maintenance and durability of response through week 52 among week 24 pasi 75 responders (nri) 0 10 20 30 40 50 60 70 80 90 100 24 28 32 36 40 44 48 52 r e sp o n se r at e , % weeks pasi 75 0 10 20 30 40 50 60 70 80 90 100 24 28 32 36 40 44 48 52 r e sp o n se r at e , % weeks spga 0/1a 70.3% 80.4% 31.3% 23.5% deucravacitinib (n = 148) placebo (withdrawal; n = 150) deucravacitinib (n = 118) placebo (withdrawal; n = 119) nri was used to impute missing data. in total, 58.7% of deucravacitinib-treated patients achieved pasi 75 at week 24 and 49.8% of deucravacitinib-treated patients achieved spga 0/1 responses at week 24. mean half-life of deucravacitinib is approximately 10 hours. aspga response is defined as a score of 0 or 1, with ≥2-point improvement from baseline. this figure shows data for all spga 0/1 responders among week 24 pasi 75 responders. nri, nonresponder imputation; pasi 75, ≥75% reduction from baseline in psoriasis area and severity index; qd, once daily; spga 0/1, static physician’s global assessment score of 0 or 1. conclusions • in the phase 3 poetyk pso-1 and pso-2 trials, deucravacitinib was efficacious through 52 weeks in patients with moderate to severe plaque psoriasis — clinical responses improved through week 24 and were maintained in patients who received continuous deucravacitinib treatment through week 52 — week 52 responses in patients who switched from placebo to deucravacitinib treatment at week 16 were comparable to those observed with continuous deucravacitinib treatment from day 1 • durable responses were observed after withdrawal of treatment in week 24 responders • the results of this 52-week efficacy analysis are consistent with those of the primary analyses of pso-1 and pso-2 at week 163 • deucravacitinib, a once-daily oral drug, has the potential to become an efficacious and well-tolerated treatment choice for patients with moderate to severe plaque psoriasis references 1. burke jr, et al. sci transl med. 2019;11:1-16. 2. wrobleski st, et al. j med chem. 2019;62:8973-8995. 3. armstrong a, et al. presented at the annual meeting of the american academy of dermatology; april 23-25, 2021. 4. blauvelt a, et al. presented at eadv 30th congress; 29 september−2 october 2021. poster p1391. acknowledgments • these clinical trials were sponsored by bristol myers squibb • writing and editorial assistance were provided by lisa feder, phd, of peloton advantage, llc, an open health company, parsippany, nj, usa, funded by bristol myers squibb disclosures • rbw: consulting fees: abbvie, almirall, amgen, boehringer ingelheim, celgene, eli lilly, janssen, leo pharma, novartis, pfizer, sanofi, ucb, and xenoport; research grants: abbvie, almirall, amgen, celgene, eli lilly, janssen, leo pharma, novartis, pfizer, and ucb; honorarium: biogen • awa: grants and personal fees: abbvie, bristol myers squibb, eli lilly, janssen, leo pharma, and novartis; personal fees: boehringer ingelheim/parexel, celgene, dermavant, genentech, glaxosmithkline, menlo therapeutics, merck, modernizing medicine, ortho dermatologics, pfizer, regeneron, sanofi genzyme, science 37, sun pharma, and valeant; grants: dermira, kyowa hakko kirin, and ucb, outside the submitted work • mg: advisory board, principal investigator, and lecture fees: abbvie, galderma, leo pharma, pfizer, and regeneron; advisory board and lecture fees: actelion; principal investigator and consulting fees: akros pharma; advisory board, principal investigator, lecture fees, and consulting fees: amgen, boehringer ingelheim, celgene, eli lilly, janssen, novartis, sanofi genzyme, and valeant; principal investigator: arcutis, bristol myers squibb, dermira, glaxosmithkline, medimmune, merck, roche laboratories, and ucb; principal investigator and lecture fees: glenmark • bs: consultant (honoraria): abbvie, almirall, amgen, arcutis, arena, aristea, asana, boehringer ingelheim, bristol myers squibb, connect biopharma, dermavant, eli lilly, equillium, glaxosmithkline, immunic therapeutics, janssen, leo pharma, maruho, meiji seika pharma, mindera, novartis, ortho dermatologics, pfizer, regeneron, sanofi genzyme, sun pharma, ucb, ventyxbio, and vtv therapeutics; speaker: abbvie, eli lilly, janssen, and sanofi genzyme; co-scientific director (consulting fee): corevitas’ (corrona) psoriasis registry; investigator: abbvie, cara, corevitas’ (corrona) psoriasis registry, dermavant, dermira, and novartis • dt: grant/research support, consultant, scientific advisory board speakers bureau: abbvie, almirall, amgen, biogen idec, boehringer ingelheim, bristol myers squibb, eli lilly, galapagos, galderma, janssen-cilag, leo pharma, novartis, pfizer, regeneron, roche, sandoz-hexal, sanofi, target-solution, and ucb • si: grants and personal fees: abbvie, eisai, janssen, kyowa kirin, leo pharma, maruho, sun pharma, taiho yakuhin, tanabe mitsubishi, and torii yakuhin; personal fees: amgen (celgene), bristol myers squibb, eli lilly, daiichi-sankyo, novartis, and ucb • hs: clinical investigator: abbvie, amgen, boehringer ingelheim, bristol myers squibb, eli lilly, janssen, leo pharma, novartis, and sun pharma • ls: consultant, paid investigator, and/or speaker: amgen, anacor, abbvie, ascend, astellas, astrazeneca, blaze bioscience, bristol myers squibb, boehringer ingelheim, botanix, celgene, dermira, eli lilly, galderma, genentech, glaxosmithkline, hexima, janssen, leo pharma, mayne, medimmune, merck (msd), merck-serono, novartis, otsuka, pfizer, phosphagenics, photon md, regeneron, roche, samumed, sanofi genzyme, shr, sun pharma anz, trius, ucb, and zai lab • njk: advisory board, consulting fees: abbvie, boehringer ingelheim, bristol myers squibb, celgene, eli lilly, janssen, leo pharma, novartis, principia, regeneron, sanofi genzyme, sun pharma, and ucb; grant support/ principal investigator: abbvie, amgen, argenx, bristol myers squibb, celgene, chemocentryx, eli lilly, galderma, kyowa hakko kirin, leo pharma, menlo, principia, prothena, rhizen, syntimmune, trevi, and xbiotech; speaker: abbvie, eli lilly, janssen, novartis, regeneron, and sanofi genzyme • mz: consultant (honoraria), clinical investigator, and lecture fees: abbvie, boehringer ingelheim, bristol myers squibb, eli lilly china, leo pharma china, novartis china, pfizer, sanofi china, and xian-janssen • ec, jt, sk, rmk, and sb: employees and shareholders: bristol myers squibb • ab: scientific adviser and/or clinical study investigator: abbvie, aligos, almirall, arena, athenex, boehringer ingelheim, bristol myers squibb, dermavant, eli lilly, evommune, forte, galderma, incyte, janssen, leo pharma, novartis, pfizer, rapt, regeneron, sanofi genzyme, sun pharma, and ucb skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 631 research letter the usmle step 1 transitions to pass/fail scoring: perceptions of dermatology residents mara trifoi, bs1 and lauren claire hollins, md2 1penn state college of medicine, hershey, pa 2penn state university department of dermatology, hershey, pa the usmle step 1 exam has been a critical objective tool for residency applications, often used during the initial screening process to distinguish between applicants.1 competitive residency programs such as dermatology and plastic surgery have traditionally required a very high step 1 scores for successful matriculates.2 as of january 2022, the usmle step 1 exam shifted to a binary scoring system consisting of only a pass/fail report.3 the purpose of this study was to gauge perceptions of current dermatology residents regarding this scoring change. a 21-item survey tool was delivered utilizing redcap to the association of professors of dermatology (apd) email listserv who subsequently distributed the survey to residents in their programs in december 2021. responses were attained using a 5point likert scale, which was reduced to a 3 abstract background: the usmle step 1 exam has been a critical objective tool for residency applications, and given the recent score change to a binary pass/fail system it is essential for programs and future residency applicants to understand the implications of this score change. methods: a survey containing 21 items was dispensed through redcap utilizing an established email list of all dermatology program directors (pds) who then distributed the survey to residents in their programs in december 2021. 132 residents completed the survey. perceptions regarding the usmle step 1 scoring change were probed. results: out of the 132 residents surveyed, the highest proportion of respondents were pgy2 (36.4% [48/132]) and pgy3 (25.8% [34/132]). of that group, most of them (74.2% [98/132]) achieved a self-reported score of 240 or higher on their usmle step 1 exam which they deemed to not be an accurate assessment of their medical knowledge (53.8% [71/132]), yet most (69.7% [92/132]) disagreed with step 1 changing to a pass/fail scoring system. similarly, 65% (86/131) opposed step 2 ck also going pass/fail. the majority of respondents agreed that there will be increased emphasis placed on research (90.0% [118/131]), extracurricular involvement (76.5% [101/132]) and the step 2 ck score (96.21% [127/132]). further, 82.3% (107/130) of respondents agreed that more students pursuing a dermatology residency will need to take a gap year. conclusion: according to current dermatology residents, the usmle step 1 exam score change to a binary scoring system will lead to more emphasis being placed on the step 2ck exam, research, and extracurricular activities. skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 632 table 1. resident perspectives on usmle step 1 pass/fail score change (n=132) statement disagree neutral agree in terms of the usmle exams i believe… step 1 should be pass/fail 92/132 (69.7%) 21/132 (9.1%) 19/132 (14.4%) step 1 gives an accurate assessment of medical knowledge 71/132 (53.8%) 33/132 (25.0%) 28/132 (21.1%) step 2 ck should be pass/fail 86/131 (65.6%) 21/131 (16.0%) 24/131 (18.3%) with step 1 transitioning to pass/fail scoring i believe… more recidency programs will emphasize the step 2 ck score 3/132 (0.22%) 2/132 (1.5%) 127/132 (96.2%) more importance will be placed on research 4/131 (3.1%) 9/131 (6.9%) 118/131 (90.0%) more importance will be placed on extracurricular involvement 9/132 (6.8%) 22/132 (16.7%) 101/132 (76.5%) more students pursuing a dermatology residency will take a gap year 4/130 (3.1%) 19/130 (14.6%) 10/130 (82.3%) skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 633 point scale for data analysis (table 1). the institutional review board at penn state hershey medical center approved the study. the survey was emailed to 368 apd faculty who were asked to distribute the survey to their residents, and 132 residents completed the survey. the majority of respondents were pgy2 (36.4% [48/132]) and pgy3 (25.8% [34/132]) and scored a 240 or higher on their usmle step 1 exam (74.2% [98/132]) which they deemed to not be an accurate assessment of their medical knowledge (53.8% [71/132]). most of the respondents (69.7% [92/132]) disagreed with step 1 moving to pass/fail and 65.6% (86/131) opposed step 2 ck also going pass/fail. the majority of respondents agreed that increased emphasis would be placed on research (90.0% [118/131]), extracurricular involvement (76.5% [101/132]) and the step 2 ck score (96.21% [127/132]). further, 82.3% (107/130) of respondents agreed that more students pursuing a dermatology residency would require a research year. these findings highlight the perceived potential implications the step 1 score change will have from the view of current dermatology residents. a recent survey of dermatology program directors (pds) echoed many of the sentiments expressed by dermatology residents, with 61.4% of pds disagreeing with the scoring change and 78.2% of them stating they would now require a step 2 ck score in the electronic residency application service (eras). 4 the intention of the federation of state medical boards (fsmb) and the national board of medical examiners (nbme) announcement to change scoring was meant to reflect the shift towards a more holistic residency application review process while improving the medical student experience as they transition to residency.3 additionally, for less diverse specialties, the change may help to increase numbers of underrepresented in medicine (urm) students, as holistic reviews may better evaluate the unique and often difficult journeys to and through medicine many urms face, which are not always captured by numerical scores.5 the field of dermatology was identified as the second least diverse field in a study conducted in 2020, highlighting the importance of decreasing barriers for urms.6 however, this and other studies have identified that residency programs may simply shift to emphasizing the still numerical step 2 ck score.4 one limitation of the study includes the includes the possible implicit bias present among our study participants, considering most participants scored a 240 or higher on their step 1 score (74.2% [98/132]). individuals that achieved higher scores on the exam may be more likely to continue supporting a numerical scoring system. dermatology residencies will need to prepare for and implement novel review processes, such as placing more focus on research, clinical rotation evaluations and extracurricular involvement in lieu of numbered scoring measures previously utilized. future studies are needed to elucidate the intended and unintended outcomes of this step 1 scoring change. conflict of interest disclosures: none funding: none corresponding author: maria trifoi penn state college of medicine 162a university manor east phone: (610) 607-9642 email: mtrifoi@pennstatehealth.psu.edu references: skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 634 1. berner es, brooks cm, erdmann jb. use of the usmle to select residents. acad med. 1993;68 (10):753759. 2. national resident matching program. charting outcomes in the match: u.s allopathic seniors, 2018. 2nd ed. national resident matching program; july 2018. accessed february 5, 2022. https://www.nrmp.org/wpcontent/uploads/2018/06/chartingoutcomes-in-the-match-2018-seniors.pdf 3. federation of state medical boards. usmle program announces upcoming policy changes https://www.fsmb.org/advocacy/newsreleases/usmle-program-announcesupcoming-policy-changes/. published 2020. accessed novemeber 5, 2022. 4. patrinely jr jr, zakria d, drolet bc. usmle step 1 changes: dermatology program director perspectives and implications. cutis. 2021 jun;107(6):293-294. doi: 10.12788/cutis.0277. pmid: 34314311. 5. the impact of united states medical licensing exam (usmle) step 1 cutoff scores on recruitment of underrepresented minorities in medicine: a retrospective crosssectional study. health sci rep. 2020;3(2):e2161. published 2020 apr 20. doi:10.1002/hsr2.161. 6. akhiyat s, cardwell l, sokumbi o. why dermatology is the second least diverse specialty in medicine: how did we get here? clin dermatol. 2020 may-jun;38(3):310-315. doi: 10.1016/j.clindermatol.2020.02.005. epub 2020 feb 19. pmid: 32563342. skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 700 brief article cutaneous acanthamoeba infection presenting with granulomatous vasculitis meredith park, bs1, paul b. googe, md2, vimal k. derebail, md, mph3, manish k. saha, md3, eduard matkovic, md4,5, jennifer r. cope, md, mph4, ibne karim m. ali, ms, phd4, carolyn ziemer, md, mph2, sam wu, md2 1 school of medicine, university of north carolina at chapel hill, chapel hill, nc 2 department of dermatology, university of north carolina at chapel hill, chapel hill, nc 3 division of nephrology and hypertension, department of medicine, university of north carolina at chapel hill, chapel hill, nc 4 national center for emerging and zoonotic infectious diseases, centers for disease control and prevention, atlanta, ga 5 department of pathology and laboratory medicine, university of wisconsin, madison, wi free-living amebae from the acanthamoeba genus are common in soil, water and dust. they exist as trophozoites in favorable conditions and as cysts in nutrient poor conditions.1 cutaneous acanthamoebiasis due to acanthamoeba is extremely rare, predominantly occurring in immunosuppressed individuals.2 disseminated acanthamoeba infection carries a poor prognosis, with mortality over 70%, and 100% in patients with central nervous system (cns) involvement.2 cns involvement is thought to occur from hematogenous spread after cutaneous or nasal exposure.1 therapeutics for acanthamoeba infection are poorly studied and numerous antimicrobial agents have been employed with varying response.2,3 we describe a fatal case of invasive acanthamoeba infection. abstract cutaneous acanthamoebiasis is a rare diagnosis that carries a mortality rate of over 70%.2 this disease predominantly affects immunocompromised individuals, though infections have been reported in immunocompetent individuals.2 we report a fatal case of cutaneous acanthamoeba infection in a patient with granulomatous vasculitis on biopsy, initially thought to be antineutrophil cytoplasmic antibody (anca)-negative vasculitis. the patient primarily presented with ulcerating nasal lesions, which subsequently developed into widespread cutaneous lesions. diagnosis was made months after presentation when amebae were identified during histopathological examination of biopsies obtained repeatedly after the patient failed to improve on standard therapies for anca-negative vasculitis. treatment was unsuccessful, and the patient died due to complications of widespread acanthamoeba infection. cutaneous acanthamoebiasis should be considered in the differential diagnosis of granulomatous vasculitis that fails to improve on standard therapies. early detection and treatment may improve outcomes and reduce mortality in this highly fatal infection. introduction skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 701 a 52-year-old woman with type 2 diabetes mellitus and recurrent marginal zone lymphoma in remission presented with erythematous and subcutaneous nodules on her right upper arm and both legs. her lymphoma diagnosis was 25 years prior to her skin lesions and recurred five and 17 years after her diagnosis. she initially received radiation, then 6 cycles of cyclophosphamide, vincristine and prednisolone for her first recurrence, and 6 cycles of rituximab with bendamustine (rbendamustine) for her second recurrence. biopsy of the nodules showed granulomatous dermatitis, concerning for sarcoidosis, without identifiable organisms. blood counts, electrolytes and inflammatory markers a few months earlier were unremarkable. full body computed tomography one year prior showed no hilar adenopathy. concurrently, she was treated by otolaryngology for nasal septal abscesses with aspergillus and septal perforation. after seven months, she developed an erythematous infiltrative plaque with overlying yellow crust on the nose encompassing nasal tip, nasal side walls, right medial cheek, and right upper cutaneous lip (figure 1). both lower extremities had violaceous, indurated nodules and plaques. she received intralesional triamcinolone and oral minocycline. a month later, due to lesion progression and concern for vasculitis, she was started on hydroxychloroquine and methotrexate. within three weeks the nasal lesion extended to the medial cheeks bilaterally and upper cutaneous lip. two lesions on her lower extremities became ulcerated with gray borders. she was admitted and treated with prednisone and an increased dose of methotrexate. figure 1. erythematous infiltrative plaque with overlying yellow crust on the nose and upper lip. shortly after discharge, she required another admission after the lesion progressed to erosions with plaques of thick yellow-brown crust encompassing the entire nose, medial cheeks, upper cutaneous and mucosal lip. she received pulse-dose steroids and intravenous cyclophosphamide. one month later was re-admitted when the lesion coalesced, creating a dry, brown plaque of the central face with necrotic nasal cartilage. she received oral cyclophosphamide and prednisone. repeat testing for hiv, tuberculosis, antinuclear antibodies, antineutrophil cytoplasmic antibody (anca), acid-fast bacterial culture and smear, and fungal studies were negative. repeat biopsies showed small vessel vasculitis with necrosis, granulomatous inflammation, and arteritis which continued to be interpreted as anca-negative granulomatosis with polyangiitis. tissue cultures grew pansensitive methicillin-susceptible staphylococcus aureus, subsequently treated with intravenous vancomycin. she received intravenous immunoglobulin intermittently for low immunoglobulin levels, initially concerning for common variable immunodeficiency, though later thought case report skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 702 unlikely. despite continued treatment with pulse-dose steroids and cyclophosphamide, a month later her facial lesion evolved to a dry necrotic eschar replacing the entire nose and medial cheeks. her upper lip was mostly lost with underlying dental structures exposed (figure 2). scattered nodules with eschar and deep ulceration developed on her chest and extremities. figure 2. dry necrotic eschar encompassing the nose, medial cheeks, and upper lip. the patient became febrile, tachycardic and was treated for presumed sepsis. repeat deep tissue biopsy and review of previous biopsies showed very rare, large, rounded mononucleated cells with vacuolated cytoplasm and centrally located nuclei with a dense, slightly eosinophilic structure in the nucleoplasm suspicious for trophozoites. these findings suggested tissue invasive acanthamoebiasis, confirmed by the centers for disease control and prevention (cdc) via immunohistochemistry assay to be acanthamoeba species (figure 3). brain imaging showed no evidence of cns involvement. immunosuppressive medications and antibiotics were stopped. despite treatment with miltefosine, fluconazole, oral and topical sulfadiazine, pentamidine, flucytosine, and topical ketoconazole, the patient developed sepsis, kidney failure, and respiratory failure and died 15 months after initial presentation. figure 3. large, rounded mononucleated cells with vacuolated cytoplasm and centrally located nuclei with a dense, slightly eosinophilic structure in the nucleoplasm suspicious for trophozoites. the diagnosis of acanthamoebiasis requires a high index of suspicion, given its rarity and ability to mimic other pathologies.1,2,4 lesions of acanthamoeba infection are usually described as erythematous or violaceous intradermal or subcutaneous nodules.2 these lesions typically enlarge, ulcerate, developing into necrotic eschar, as illustrated here. pathology often shows nonspecific granulomatous inflammation and previously reported cases were initially mistaken for discussion skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 703 fungal infections and vasculitides.1,2,4 acanthamoeba species may infect the cns causing granulomatous amoebic encephalitis, which shows necrotizing or granulomatous response on pathologic examination.5 granulomatous vasculitis is often associated with anca vasculitis, and less commonly other etiologies such as lymphomatoid granulomatosis, rheumatoid vasculitis, or herpes simplex virus.7 given the severity of acanthamoeba infection, cutaneous acanthamoebiasis should be considered in the differential diagnosis of granulomatous vasculitis that fails to improve on standard therapies and with clinical history suggestive of exposure. while histopathology is crucial to diagnosis, more sensitive molecular analysis of tissue with polymerase chain reaction (pcr) (available through the cdc or mayo medical laboratories), may allow earlier detection.3,8,9 this real-time pcr assay is able to detect one amoeba per sample.10 early diagnosis of acanthamoeba infection is essential for appropriate management that may reduce likelihood of death.4,8 historically, cutaneous acanthamoeba infections have almost exclusively been seen in immunocompromised individuals.2,11 while this patient was not on immunosuppression initially, she had diabetes mellitus which increases the risk of skin infections.12 the patient’s exposure was thought to be from swimming in a fresh water lake or through nasal lavage with well water. management of cutaneous acanthamoeba infection is not well studied and no consensus on optimal pharmacologic therapy exists.2,4 previously reported cases were treated with various antimicrobial agents with variable effect.2– 4,8,9,11 treatment with flucytosine and miltefosine has been associated with better responses, although rarely curative.2,3 as illustrated here, the toxic effects of these antimicrobial agents must be considered during treatment. acanthamoeba infection is a rare cause of cutaneous lesions that may mimic granulomatous inflammatory diseases including vasculitis. given its high potential mortality, patients with worsening lesions despite conventional therapies and granulomatous vasculitis on pathology should be further evaluated for amoebiasis either by meticulous histopathology or by pcr. disclaimer: the findings and conclusions in this report are those of the authors, and do not necessarily represent the official positions of the centers for disease control and prevention. conflict of interest disclosures: none funding: none corresponding author: meredith park, bs university of north carolina at chapel hill school of medicine 321 s columbia st. chapel hill, nc 27599 email: meredith_park@med.unc.edu references: 1. murakawa gj, mccalmont t, altman j, telang gh, kantor gr, berger tg. acanthamebiasis with. published online 2015:2-7. 2. paltiel m, powell e, lynch j, baranowski b, martins c. disseminated cutaneous acanthamebiasis: a case report and review of the literature. cutis. 2004;73(4):241-248. 3. aichelburg ac, walochnik j, assadian o, et al. successful treatment of disseminated acanthamoeba sp. infection with miltefosine. emerg infect dis • www.cdc.gov/eid •. 2008;14(11). doi:10.3201/eid1411.070854 4. steinberg jp, galindo rl, kraus es, ghanem kg. disseminated acanthamebiasis in a renal transplant recipient with conclusion skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 704 osteomyelitis and cutaneous lesions: case report and literature review. clin infect dis. 2002;35(5):43-49. doi:10.1086/341973 5. wiley ca, safrin re, davis ce, et al. acanthamoeba meningoencephalitis in a patient with aids. source j infect dis. 1987;155(1):130-133. accessed may 15, 2022. https://about.jstor.org/terms 6. schuster fl, guglielmo bj, visvesvara gs. in-vitro activity of miltefosine and voriconazole on clinical isolates of free-living amebas: balamuthia mandrillaris, acanthamoeba spp., and naegleria fowleri. j eukaryot microbiol. 2006;53(2):121-126. doi:10.1111/j.1550-7408.2005.00082.x 7. pagnoux c, bienvenu b, guillevin l. the spectrum of granulomatous vasculitides. futur rheumatol. 2006;(6):729-750. doi:10.2217/17460816.1.6.729 8. morrison ao, morris r, shannon a, lauer sr, guarner j, kraft cs. disseminated acanthamoeba infection presenting with cutaneous lesions in an immunocompromised patient: a case report, review of histomorphologic findings, and potential diagnostic pitfalls. am j clin pathol. 2016;145(2):266-270. doi:10.1093/ajcp/aqv081 9. afshar k, boydking a, ganesh s, herrington c, michael mcfadden p. rapidly fatal disseminated acanthamoebiasis in a single lung transplant recipient. ann transplant. 2013;18(1):108-111. doi:10.12659/aot.883846 10. qvarnstrom y, visvesvara gs, sriram r, da silva aj. multiplex real-time pcr assay for simultaneous detection of acanthamoeba spp., balamuthia mandrillaris, and naegleria fowleri. j clin microbiol. 2006;44(10):35893595. doi:10.1128/jcm.00875-06 11. galarza c, ramos w, gutierrez el, et al. cutaneous acanthamebiasis infection in immunocompetent and immunocompromised patients. int j dermatol. 2009;48(12):13241329. doi:10.1111/j.13654632.2008.03786.x 12. berbudi a, rahmadika n, tjahjadi ai, ruslami r. science bentham. type 2 diabetes and its impact on the immune system. curr diabetes rev. 2020;16:442449. doi:10.2174/1573399815666191024085838 acknowledgements study funded by sol-gel technologies ltd.; poster support provided by galderma laboratories, l.p., fort worth, tx eps.p-sgt5401-03 drug microencapsulation background benefits of microencapsulation • creates a silicon dioxide (silica) microcapsule shell between the bpo and the skin5 • helps control the release rate of the drug to improve tolerability6 • can preserve the advantages of bpo while minimizing limitations6 encapsulation process4 silica is added in 5–100 repetitive cycles to build up a silica shell around the bpo 47.4 20.7 49.2 28.2 0 15 30 pe rc en ta ge o f s ub je ct s ac hi ev in g ig a su cc es s (it t) 45 60 e-bpo (n=243) 95% ci: 16.7%, 36.8% 95% ci: 10.7%, 31.3% vehicle (n=118) e-bpo (n=250) vehicle (n=122) study 1 study 2 m ea n in fla m m at or y le si on c ou nt ch an ge f ro m b as el in e e-bpo cream 5% (n=243) p <.001 p <.001 p <.001 vehicle (n=118) -20 -18 -16 -14 -12 -10 -8 -6 -4 -2 0 baseline week 2 week 4 week 8 week 12 -10.5 -5.5 -14.6 -8.7 -16.8 -10.6 -17.4 -9.5 p <.001 m ea n in fla m m at or y le si on c ou nt ch an ge f ro m b as el in e (it t) e-bpo cream 5% (n=243) p <.001 p <.001 vehicle (n=118) e-bpo cream 5% (n=250) vehicle (n=122) study 1 study 2 -17.4 -9.5 -20.3 -13.3 -25 -20 -15 -10 -5 0 m ea n in fla m m at or y le si on c ou nt ch an ge f ro m b as el in e p <.001 p <.001 p <.001 p <.001 baseline week 2 week 4 week 8 week 12 0 5 10 15 20 25 30 35 -13.0 -8.0 -16.7 -10.5 -20.0 -12.4 -20.3 -13.3 e-bpo cream 5% (n=250) vehicle (n=122) introduction • rosacea affects at least 10% of fair skinned individuals and not uncommon in black, asian, and hispanic populations1,7,8 • over 16 million people in the united states have rosacea2 • triggers for rosacea are wide-ranging and can include skin care products, cold and/or hot weather, spicy foods, and emotional stress1 • rosacea is characterized as an inflammatory disorder of the facial skin that primarily affects the cheeks, nose, chin, forehead, and eyes1 • rosacea signs present as facial erythema, flushing, papules, pustules, phymas, and telangiectasias1,7 • the disease is frequently characterized by remissions and exacerbations1 critical evaluation of benzoyl peroxide in rosacea: old challenges and new clinical opportunities with encapsulated benzoyl peroxide james q. del rosso, do1; neal d. bhatia, md2; hilary baldwin, md3; linda stein gold, md4; seemal r. desai, md5,6; sam brantman, pharmd7 1jdr dermatology research, las vegas, nv; 2therapeutics clinical research, san diego, ca; 3the acne treatment & research center, brooklyn, ny, and rutgers robert wood johnson medical center, new brunswick, nj; 4henry ford health systems, detroit, mi; 5innovative dermatology, plano, tx; 6department of dermatology, the university of texas southwestern medical center, dallas, tx; 7galderma laboratories, l.p., fort worth, tx methods co-primary endpoints • proportion of subjects with the primary measure of success, “clear” (0) or “almost clear” (1), in the investigator global assessment (iga) relative to baseline at week 12 the iga scale ranged from “clear” (0) to “severe” (4) and included the number of papules/pustules and erythema severity • absolute mean change in inflammatory lesion counts from baseline to week 12 secondary endpoints • percentage change in inflammatory lesion count from baseline to week 12 • absolute change in inflammatory lesion count from baseline to week 8 study design of the two pivotal phase 3 trials for e-bpo cream, 5% (figure 1) references 1. thiboutot d, anderson r, cook-bolden f, et al. standard management options for rosacea: the 2019 update by the national rosacea society expert committee. j am acad dermatol. jun 2020;82(6):1501-1510. 2. van zuuren ej. rosacea. n engl j med. 2017 nov 2;377(18):1754-1764. 3. tan j, steinhoff m, bewley a, et al. [published correction appears in in j dermatolog treat. 2020;31(2):210]. j dermatolog treat. 2020;31(2):168-174. 4. steinhoff m, et al. beyond the visible: rosacea and psoriasis of the face. the bmj hosted content 2020. accessed april 2021. https://hosted.bmj.com/media/images/beyond-the-visible-rosacea-andpsoriasis-of-the-face.pdf. 5. kolli ss, pecone d, pona a, et al. topical retinoids in acne vulgaris: a systematic review. am j clin dermatol. 2019 jun;20(3):345-365. 6. rosacea now estimated to affect at least 16 million americans. national rosacea society. winter 2010. accessed october 19, 2021. https://www.rosacea.org/rosacea-review/2010/winter/rosaceanow-estimated-to-affect-at-least-16-million-americans. 7. del rosso jq, tanghetti e, webster g, et al. update on the management of rosacea from the american acne & rosacea society (aars). j clin aesthet dermatol. 2019 jun;12(6):17-24. 8. gallo rl, granstein rd, kang s, et al. standard classification and pathophysiology of rosacea: the 2017 update by the national rosacea society expert committee. j am acad dermatol. 2018 jan;78(1):148-155. 9. erlich m, arie t, koifman n, et al. structure elucidation of silica-based core-shell microencapsulated drugs for topical applications by cryogenic scanning electron microscopy. j colloid interface sci. 2020 nov 1;579:778-785. 10. fireman s, toledano o, neimann k, et al. a look at emerging delivery systems for topical drug products. dermatol ther. 2011 sep-oct;24(5):477-88. summary • both phase 3 studies met the co-primary endpoints of iga success “clear” (0) or “almost clear” (1) (p <.02) and a significant reduction in the absolute mean change in inflammatory lesion counts (p <.001) versus vehicle at 12 weeks • e-bpo cream, 5%, had a well-tolerated safety profile similar to vehicle in both studies • a reduction in mean inflammatory count was seen as early as week 2 in both studies and was maintained for the entirety of each 12-week study results • a reduction in mean inflammatory count was seen as early as week 2 in both studies and was maintained for the entirety of each 12-week study (figure 4) • most subjects experienced adverse reactions that were mild or moderate in severity (table 3) • the serious adverse event reported in the treatment arm was determined by the investigators to not be related to study drug • teaes are combined from study 1 and study 2 study 1 study 2 characteristic e-bpon=243 vehicle n=118 e-bpo n=250 vehicle n=122 iga: moderate 210 (86.4%) 104 (88.1%) 227 (90.8%) 112 (91.8%) iga: severe 33 (13.6%) 14 (11.9%) 23 (9.2%) 10 (8.2%) mean lesion count (sd) 25.7 (11.07) 26.3 (12.45) 29.8 (14.00) 27.5 (13.04) median lesion count (range) 22.0 (15–69) 21.0 (15–70) 25.0 (15–70) 22.5 (15–70) mean age (years) 52.8 52.4 49.5 51.5 male 60 (24.7%) 35 (29.7%) 69 (27.6%) 35 (28.7%) female 183 (75.3%) 83 (70.3%) 181 (72.4%) 87 (71.3%) grade description 0 – clear skin clear of inflammatory papules or pustules 1 – almost clear very few small papules or pustules and very mild dull erythema are present 2 – mild few small papules or pustules and mild dull or light pink erythema are present 3 – moderate several to many small or larger papules or pustules and moderate light to bright red erythema are present 4 – severe numerous small and/or larger papules or pustules and severe erythema that is bright red to deep red are present e-bpo (n=488) vehicle (n=234) subjects reporting any teae 99 (20.3%) 39 (16.7%) serious teae 1 (0.2%) 1 (0.4%) discontinued study drug 11 (2.3%) 3 (1.3%) discontinued study 9 (1.8%) 2 (0.9%) related aes occurring in >1% of subjects treated with e-bpo application site pain 11 (2%) 2 (1%) application site erythema 11 (2%) 2 (1%) application site pruritis 6 (1%) 1 (<1%) application site edema* 4 (1%) 0 (0%) *application site edema includes application site swelling and application site edema. table 3. treatment-emergent adverse events (safety population) figure 1. two phase 3, double-blind, randomized, vehicle-controlled studies figure 5. iga success with e-bpo — study 1 subject 101021 figure 2. iga success at week 12 figure 4. mean inflammatory lesion count change from baseline figure 3. mean inflammatory lesion count change from baseline to week 12 e-bpo cream, 5% e-bpo cream, 5% (once daily) vehicle cream (once daily) 12 weeks of treatment • men and women ≥18 years of age • clinical diagnosis of moderate to severe rosacea with a baseline investigator global assessment score of 3 or 4 • ≥15 to ≤70 inflammatory lesions • ≤2 nodules randomization qd, self-applied 54 total study sites study 1 e-bpo: n=243 vehicle: n=118 study 2 e-bpo: n=250 vehicle: n=122 ke y in clu sio n cr ite ria baseline 2 4 8 12 weeks • in both studies, e-bpo cream, 5%, demonstrated statistically significant improvement in the co-primary endpoint of the number of subjects achieving “clear” or “almost clear” • in study 1, 47.4% of subjects treated with e-bpo achieved iga success at week 12 versus 20.7% of subjects treated with vehicle. in study 2, it was 49.2% versus 28.2% of subjects (figure 2) • in both studies, e-bpo demonstrated a significant reduction in inflammatory lesion counts from baseline to week 12 versus vehicle (figure 3) study 1 study 2 baseline iga 3 3 3 1 inflammatory lesions 20 23 12 7 iga 4 4 4 3 inflammatory lesions 68 25 33 21 week 4 week 8 week 12 co-primary endpoint least squares means, standard deviations, and treatment p value from an analysis of covariance with factors of treatment group, analysis center, and treatment by analysis center interaction and baseline lesion count as a covariate. negative least squares means values represent decrease from baseline. 2:1 table 1. baseline characteristics of subjects table 2. investigator global assessment (iga) scale abbreviations: e-bpo = encapsulated benzoyl peroxide; iga = investigator global assessment; itt = intent-to-treat; sd = standard deviation; teae = treatment-emergent adverse event week 4 week 8 week 12 figure 6. iga failure with e-bpo — study 1 subject 106017 baseline skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 311 brief article acne keloidalis nuchae successfully treated with halobetasol 0.01% and tazarotene 0.045% olga marushchak, do*1,2, kathryn jayne tan, md*1, maria rosa noliza encarnacion1, md, loren clark, do2, alexandra golant, md1 * both authors have contributed equally 1 department of dermatology, icahn school of medicine at mount sinai, new york, ny 2 touro college of osteopathic medicine, new york, ny acne keloidalis nuchae (akn) is a chronic inflammatory condition that predominantly affects african-american men 14-25 years of age.1 it clinically presents with skin-colored follicular papules, pustules and plaques, which may coalesce, eventually leading to keloid-like scarred lesions, fibrotic plaques and alopecia.1,2 advanced cases may present with abscesses and sinuses exuding pus.3 the lesions are usually located at the occiput and neck. the condition is thought to be triggered by skin injury, which may cause chronic irritation or occlusion of follicles, or immune reaction that may lead to the cicatricial alopecia.2,4,5 conventional treatment focuses on avoidance of exacerbation factors, utilization of topical and oral antibiotics, and decreasing inflammation with intralesional steroids.2 cryotherapy, light and laser therapies, and surgical excision demonstrated some success as well.1,2 in this case report, we present a patient with a history of akn who failed the treatment with intralesional steroids, but was successfully treated with halobetasol/tazarotene lotion. although topical retinoids have been used in akn patients, the efficacy of these agents has not been evaluated in research studies and current literature lacks reports of akn resolution with a fixed combination of halobetasol and tazarotene treatment. a 25-year-old african-american male presented to an outpatient dermatology clinic with a chief complain of hair loss and rash on the posterior scalp (figure 1) of two years abstract acne keloidalis nuchae (akn) is an idiopathic chronic inflammatory condition that predominantly affects african-american men and presents with follicular papules, pustules and plaques, which may eventually lead to keloid-like scarred lesions, fibrotic plaques, abscesses, sinuses, and alopecia. conventional treatment approach focuses on avoidance of exacerbation factors, utilization of topical and oral antibiotics, and decreasing inflammation with intralesional steroids. this is the first case showing successful treatment of akn with halobetasol 0.01% and tazarotene 0.045% lotion. although topical steroids and topical retinoids have been used as treatment options, there are no published data supporting the use of their fixed combination in patients with akn. introduction case report skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 312 duration. the rash presented as boggy erythematous pustules and papules with scaly crust on the crown, keloidal papules on the posterior neck, and erythematous papules in a beard distribution at the time of the physical examination. the review of systems was negative for fever, chills, and other constitutional symptoms. the review of medical history and medications were unremarkable. figure 1. erythematous papules and pustules on the posterior scalp prior to the treatment with halobetasol 0.01% and tazarotene 0.045% lotion. fungal workup was negative: potassium hydroxide with calcofluor white preparation revealed no fungus, and no yeast or mold were isolated on dermatophyte mycology medium. after tinea capitis was ruled out, the patient was clinically diagnosed with akn and started on clindamycin gel once a day and intralesional triamcinolone injections 5 mg/cc once a month. with little improvement after 4 months on the regimen, the patient was given a fixed combination of halobetasol 0.01% and tazarotene 0.045% lotion applied twice daily. the patient noticed a significant improvement after one month of the topical combination trial; hence, the medication was continued. at the month 4 follow-up visit, the patient noted remarkable improvement, with decrease in erythema and fewer pustules and papules (figure 2). figure 2. a significant improvement of erythema was noted after four months relative to the initial presentation. though the exact cause of akn remains unknown, the following pathogenesis has been proposed by sperling et al. antigens, mainly sebum, desquamated keratinocytes, normal skin flora, accumulate within follicular canal and attract perifollicular inflammatory cells to the isthmus of the hair follicles, leading to the damage or destruction of the sebaceous gland, as well as the follicular wall. due to the weakening of the follicular wall, an additional leakage of intrafollicular antigens may lead to further inflammation, eventually causing hair follicle rupture, follicular scarring, and the inability of hair regrowth.3,4 considering this proposed pathogenesis, the therapy should be aimed at halting the initial inflammation to prevent the subsequent cicatricial alopecia. the inflammatory discussion skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 313 component of pathogenesis is commonly addressed with steroids due to their ability to stop the production, release, and biological activity of endogenous mediators of inflammation. monthly intralesional triamcinolone acetonide alone or in combination with antibiotics, commonly topical clindamycin or erythromycin or oral tetracycline, is the treatment of first choice.1,6 topical steroids, preferably of high potency, may be used in the medical management of akn as well because of their antiinflammatory, antipruritic, and vasoconstrictive activity. in a study involving 20 african-american patients with akn, monotherapy with topical clobetasol propionate demonstrated to be effective in preventing progression and improving symptoms of mild-to-moderate cases.4 another component of pathogenesis, chronic irritation or occlusion of follicles, may be addressed with retinoids. topical retinoids, aside from their anti-inflammatory properties, normalize follicular keratinocyte maturation and desquamation, thereby decreasing follicular blockage and potential antigens that have been proposed to initiate the immune response in akn. oral retinoids, including isotretinoin, in combination with oral antibiotics and topical steroids, have previously been used to treat akn.2 however, the efficacy of topical retinoids in the treatment of akn has not been supported by any clinical trials. nor have there been studies analyzing the use of a combination of topical steroids and topical retinoid. there are other treatment options available for cases refractory to the aforementioned therapies. in one interventional study, 16 patients with akn were treated with five sessions of long-pulsed neodymium:yttrium aluminum garnet (nd:yag) laser.7 the follow-up biopsies showed significant decrease in the inflammatory infiltrate in 15 patients, while clinical symptoms significantly improved in all patients. the results of this study and other reports of successful treatment with nd:yag and diode laser suggest possible benefit of laser hair removal for akn.7-9 a prospective, randomized study of 11 patients with akn demonstrated significant decrease in lesion count after eight weeks of treatment with targeted ultraviolet b phototherapy.10 radiotherapy has been reported to lead to a full response with excellent clinical and cosmetic long-term results in a case of persistent akn.11 surgical excision is typically reserved for extensive plaqueand tumor-stage cases.6,12 although successful results of the said therapies have been reported in case reports and small studies, larger controlled trials with long-term follow-up are needed to assess the value of these interventions. a combination product containing high potency topical steroid and retinoid may be beneficial in treating mild akn and presents an affordable non-invasive therapeutic option that could increase patient compliance as well as improve quality of life. both topical steroids and retinoids have been used as treatment options; however, to the best of our knowledge, there are no published data supporting the use of their combination. this is the first case showing successful treatment of akn with a 4-month regimen of fixed halobetasol/tazarotene lotion twice a day. further investigation of the efficacy of topical halobetasol/tazarotene combination for the treatment of akn is recommended, with special attention to the long-term control of the condition in a larger sample size. conflict of interest disclosures: none funding: none conclusion skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 314 corresponding author: olga marushchak, do department of dermatology icahn school of medicine at mount sinai 5 e 98th st, 5th floor, new york, ny 10029 phone: 212-241-3288 email:omarushc2@student.touro.edu references: 1. otberg n, shapiro j. cicatricial alopecias. in: kang s, amagai m, bruckner al, enk ah, margolis dj, mcmichael aj, orringer js. eds. fitzpatrick's dermatology, 9e. mcgraw-hill; accessed february 12, 2021. 2. maranda el, simmons bj, nguyen ah, lim vm, keri je. treatment of acne keloidalis nuchae: a systematic review of the literature. dermatol ther. 2016;6(3):363–378. doi:10.1007/s13555016-0134-5 3. sperling lc, homoky c, pratt l, sau p. acne keloidalis is a form of primary scarring alopecia. arch dermatol. 2000;136(4):479–484. doi:10.1001/archderm.136.4.479 4. callender vd, young cm, haverstock cl, carroll cl, feldman sr. an open label study of clobetasol propionate 0.05% and betamethasone valerate 0.12% foams in the treatment of mild to moderate acne keloidalis. cutis. 2005 jun;75(6):317-21 pmid: 16047868. 5. ogunbiyi a. acne keloidalis nuchae: prevalence, impact, and management challenges. clin cosmet investig dermatol. 2016 dec;9:483-489. doi:10.2147/ccid.s99225 6. beckett n, lawson c, cohen g. electrosurgical excision of acne keloidalis nuchae with secondary intention healing. j clin aesthet dermatol. 2011 jan;4(1):36-39 7. esmat sm, abdel hay rm, abu zeid om, hosni hn. the efficacy of laser-assisted hair removal in the treatment of acne keloidalis nuchae; a pilot study. eur j dermatol. 2012;22(5):645-650. doi:10.1684/ejd.2012.1830 8. dragoni f, bassi a, cannarozzo g, bonan p, moretti s, campolmi p. successful treatment of acne keloidalis nuchae resistant to conventional therapy with 1064-nm nd:yag laser. g ital dermatol venereol. 2013;148(2):231-232. 9. shah gk. efficacy of diode laser for treating acne keloidalis nuchae. indian j dermatol venereol leprol. 2005;71(1):31-34. doi:10.4103/03786323.13783 10. okoye ga, rainer bm, leung sg, et al. improving acne keloidalis nuchae with targeted ultraviolet b treatment: a prospective, randomized, split-scalp comparison study. br j dermatol. 2014;171(5):1156-1163. doi:10.1111/bjd.13119 11. millán-cayetano jf, repiso-jiménez jb, del boz j, de troya-martín m. refractory acne keloidalis nuchae treated with radiotherapy. australas j dermatol. 2017;58(1):e11-e13. doi:10.1111/ajd.12380 12. gloster hm jr. the surgical management of extensive cases of acne keloidalis nuchae. arch dermatol. 2000;136(11):1376-1379. doi:10.1001/archderm.136.11.1376 acknowledgements: medical writing support was provided by prescott medical communications group (chicago, il) with financial support from ortho dermatologics; ortho dermatologics is a division of bausch health us, llc • presented at the fall clinical dermatology conference for pas and nps • june 3-5, 2022 • scottsdale, az synopsis � truncal acne (occurring on the chest and back) is common among patients with facial acne,1-3 though its pathophysiology may be somewhat different4,5 � as there are no specific guidelines for the treatment of truncal acne, facial acne treatment guidelines are often the basis for its management3 � successful treatment of truncal acne is complicated by the involvement of a large body surface area that is typically covered in clothing3 � topical vehicles that provide ease of spreadability, rapid cutaneous penetration/effective drug delivery, and lack of residue are highly desirable for truncal acne treatment1 � a lower-dose tazarotene 0.045% lotion formulation (arazlo®; ortho dermatologics) was developed utilizing polymeric emulsion technology (figure 1)6 • this highly spreadable lotion formulation was developed to allow for more efficient delivery of tazarotene into dermal layers • in phase 1 studies, this lotion demonstrated low irritation/contact dermatitis potential and no allergic sensitization7 objectives � study 1: to summarize the efficacy, safety, and tolerability of tazarotene 0.045% lotion in the treatment of truncal acne � study 2: to evaluate the spreadability of tazarotene 0.045% lotion and trifarotene 0.005% cream on the trunk figure 1. polymeric emulsion technology for tazarotene 0.045% lotion 1-2 μm ① ② ③ ① polymeric matrix holds water and water-soluble hydrating agents within a 3-d mesh ② droplets of tazarotene and oil-soluble moisturizing agents held apart by the 3-d mesh ③ 3-d mesh allows for uniform distribution of tazarotene and moisturizing agents study 2: spreadability tazarotene 0.045% lotion vs trifarotene 0.005% cream8 study 2 design • double-blind split-body study of 30 healthy adults (18–59 years) • each product (0.1 ml) was applied to a 10 cm wide area on one side of participants’ backs and moved down the back until it would no longer spread; area of spread was then determined 160 0 40 80 120 167.0 tazarotene 0.045% lotion m e a n a re a o f p ro d u ct s p re a d ( cm 2 ) 130.3 200 trifarotene 0.005% cream tazarotene 0.045% lotion trifarotene 0.005% cream mean spreadability of tazarotene lotion and trifarotene cream (n=30) participant example ***p<0.001 vs trifarotene 0.005% cream. mean difference: 36.7 cm2 • on average, skin coverage with tazarotene 0.045% lotion was ~30% greater than with trifarotene 0.005% cream tazarotene 0.045% lotion for truncal acne: efficacy, safety, and spreadability leon h kircik, md1-3; zoe d draelos, md4; eric guenin, pharmd, phd, mph5 1icahn school of medicine at mount sinai, new york, ny; 2indiana university medical center, indianapolis, in; 3physicians skin care, pllc, dermresearch, pllc, and skin sciences, pllc, louisville, ky; 4dermatology consulting services, pllc, high point, nc; 5ortho dermatologics, bridgewater, nj* *ortho dermatologics is a division of bausch health us, llc fig conclusions � tazarotene 0.045% lotion utilizes polymeric emulsion technology to enhance hydration, moisturization, and skin barrier function � tazarotene 0.045% lotion led to significant reductions in truncal acne severity and lesion counts; ~90% of participants achieved clear or almost clear skin with 12 weeks of once-daily use and most participants had no tolerability issues � this easy-to-apply tazarotene lotion has sensory and aesthetic properties preferred by patients6 and resulted in ~30% greater skin coverage compared with trifarotene cream • less product needed to cover the same skin area equals more applications per unit volume references 1. del rosso jq. cutis. 2006;77:285–289. 2. dréno b, et al. jeadv. 2015;29(6):1096–1106. 3. poli f, et al. jeadv. 2020;34(10):2241–2246. 4. short rw, et al. pediatr dermatol. 25(1):126–128. 5. kim br, et al. dermatol. 231:87–93. 6. tanghetti ea, et al. j dermatol treat. 2019;sept 26:1–8. 7. kircik lh, et al. j dermatol treat. 2121;aug 30:1–9. 8. draelos zd, et al. j drugs dermatol. 2021;21(3):250–257. author disclosures leon h kircik has acted as an investigator, advisor, speaker, and consultant for ortho dermatologics. zoe d draelos received funding from ortho dermatologics to conduct the research presented here. eric guenin is an employee of ortho dermatologics and may hold stock and/or stock options in its parent company. study 1: efficacy, safety, and tolerability in truncal acne tazarotene 0.045% lotion • most participants had no tolerability issues • there were no signi�cant changes from baseline to week 12 in any tolerability assessment total lesion reductions -100% -60% -40% -20% 0% baseline week 4 week 8 week 12 ls m e a n p e rc e n t c h a n g e f ro m b a se lin e -80% -44.9% *** tazarotene 0.045% lotion (n=19) -67.7% *** -82.3% *** ls mean percent changes from baseline: il -49.4%*** -63.8%*** -83.3%*** nil -7.6%* -59.3%** -64.3%** cutaneous tolerability and safety 0% 40% 60% 80% 100% p e rc e n ta g e o f p a rt ic ip a n ts 20% bl, baseline. there were no adverse events related to tazarotene treatment in this study. clear/almost clear skin 0% 40% 60% 80% 100% baseline week 4 week 8 week 12 p e rc e n ta g e o f p a rt ic ip a n ts 20% *** 21% tazarotene 0.045% lotion (n=19) *** 47% *** 89% truncal ef�cacy *p<0.05; **p<0.01; ***p<0.001 vs baseline. il, in�ammatory lesions; ls, least squares; nil, nonin�ammatory lesions. severity: none trace mild patient preference questionnaire ointment cream lotion spray gel not all participants responded to all items on the questionnaire; percentages for each item are based upon the number of participants who responded to that item. percentage of participants 6 11 17 67 6 11 67 116 21 32 5 1132 18 29 6 641 53 18 6 1212 product rank: 5=liked least 4 3 2 1=liked best ranked preference for past skin medicines percentage of participants ratings of tazarotene 0.045% lotion 20 40 60 80 100 percentage of participants rating the lotion as “good” or “excellent” compared to other medicines easy to use continue daily activities large surface area application lotion disappears soft skin 0 88% 83% 80% 75% 64% study 1 design • participants aged ≥12 years • moderate truncal acne (investigator’s global assessment score = 3) • once-daily treatment with tazarotene 0.045% lotion for 12 weeks • age (mean): 24.1 years • sex: 52.6% female • race: 52.6% white, 36.8% black, 10.5% biracial demographics at week 12: • ~90% achieved clear or almost clear skin • >80% reductions from baseline in total lesion counts bl wk12 11% 90% 100% peeling bl wk12 11% 16% 74% 5% 21% 74% erythema bl wk12 11% 90% 100% dryness bl wk12 95% 5% 95% oiliness 5% bl wk12 16% 84% 11% 5% 84% pruritus bl wk12 5% 95% 11% 5% 84% burning • overall, participants preferred lotions over other types of topical treatments • most participants (64–88%) rated attributes of tazarotene 0.045% lotion as “good” or “excellent” in comparison to other medications objectives to evaluate efficacy and safety of bimekizumab (bkz) in patients with moderate plaque psoriasis over two years using data from five phase 3/3b trials. introduction • bkz has demonstrated high levels of efficacy in patients with moderate to severe plaque psoriasis.1–4 • here, we consider bkz efficacy and safety in patients with moderate psoriasis. materials and methods • moderate psoriasis was defined as body surface area (bsa) ≥10%–≤15%, psoriasis area and severity index (pasi) ≥12, and investigators global assessment (iga)=3 at baseline. • data were pooled from be sure, be vivid, be ready, the first year of the be bright open label extension (ole), and be radiant (48-week double-blinded period and ongoing ole).1–5 • patients received bkz 320 mg every 4 weeks (q4w) to week 16, then either bkz q4w or every 8 weeks (q8w) maintenance dosing (figure 1). • efficacy outcomes are reported through two years for all bkz treated patients, regardless of dosing regimen. • data are reported using modified non-responder imputation (mnri), nri, and as the observed case (oc). – for mnri, patients who discontinued due to lack of efficacy, entered the be ready open-label escape arm, or discontinued treatment due to an adverse event (ae) prior to ole entry were considered non-responders at subsequent timepoints; multiple imputation was used for all other missing data. • treatment-emergent aes (teaes), evaluated as exposure-adjusted incidence rates (eairs) per 100 patient-years, are reported for patients with moderate psoriasis who received ≥1 bkz dose. the percentage of patients who experienced a teae is also reported. results • at baseline, 301 patients with moderate psoriasis were randomized to bkz; 269 continued to the oles. • baseline characteristics for patients with moderate psoriasis were similar to the bkz-randomized study population with moderate to severe plaque psoriasis (except for criteria used to distinguish between moderate and moderate to severe psoriasis; table 1). • high levels of pasi ≤2, pasi 100, and bsa ≤1% responses were observed in bkz-treated patients at week 16. similarly high response levels were reported after two years of treatment (ole week 48) among patients who entered the oles (figure 2). • teaes occurred in 90.7% of patients and were lower with bkz q8w vs q4w. serious teaes and teaes leading to discontinuation were low (table 2). • the most common teaes were nasopharyngitis, oral candidiasis, and upper respiratory tract infections (table 2; table 3). • oral candidiasis eairs were lower with bkz q8w vs q4w. the majority of oral candidiasis teaes were mild/moderate (98.2%). two patients with oral candidiasis discontinued bkz. • similar to the overall study population,6 eairs of safety topics of interest were low in moderate psoriasis patients (table 2; table 3). • occurrence of teaes and serious teaes generally decreased or remained comparable over time (table 3). summary presented at the 42nd annual fall clinical dermatology conference | las vegas, nv | 20–23 october 2022 conclusions results demonstrate that continuously high levels of skin clearance were seen with bkz over two years in patients with moderate psoriasis. bkz was well-tolerated over two years in patients with moderate psoriasis. andrew blauvelt,1 linda stein gold,2 melinda gooderham,3 bruce strober,4 andreas pinter,5 jose-manuel carrascosa,6 paolo gisondi,7 jonathan bleier,8,9 cynthia madden,10 delphine deherder,11 natalie nunez gomez,12 richard b. warren13 bimekizumab efficacy and safety through two years in patients with moderate psoriasis: analysis of pooled data from five phase 3/3b clinical trials previously presented at eadv 2022 institutions: 1oregon medical research center, portland, oregon, usa; 2henry ford health system, detroit, michigan, usa; 3skin centre for dermatology, probity medical research, peterborough, ontario, canada and queen’s university, kingston, ontario, canada; 4yale university, new haven, connecticut, usa and central connecticut dermatology research, cromwell, connecticut, usa; 5university hospital frankfurt, frankfurt am main, germany; 6hospital universitari germans trias i pujol, uab, igtp, badalona, barcelona, spain; 7university of verona, verona, italy; 8veramed, london, uk; 9ucb pharma, slough, uk; 10ucb pharma, raleigh, north carolina, usa; 11ucb pharma, braine-l’alleud, belgium; 12ucb pharma, monheim, germany; 13dermatology centre, salford royal nhs foundation trust, manchester nihr biomedical research centre, the university of manchester, manchester, uk. references: 1reich k et al. lancet 2021;397:487–98, nct03370133; 2gordon kb et al. lancet 2021;397:475–86, nct03410992; 3warren rb et al. n engl j med 2021;385:130–41, nct03412747; 4reich k et al. n engl j med 2021;385:142–52, nct03536884; 5be bright: clinicaltrials.gov/ct2/show/nct03598790; 6gordon kb et al. jama dermatol 2022; published online ahead of print. author contributions: substantial contributions to study conception/design, or acquisition/analysis/interpretation of data: ab, lsg, mg, bs, ap, jmc, pg, jb, cm, dd, nng, rbw; drafting of the publication, or revising it critically for important intellectual content: ab, lsg, mg, bs, ap, jmc, pg, jb, cm, dd, nng, rbw; final approval of the publication: ab, lsg, mg, bs, ap, jmc, pg, jb, cm, dd, nng, rbw. author disclosures: ab: served as a speaker, scientific adviser, and/or clinical study investigator for abbvie, abcentra, aligos, almirall, amgen, arcutis, arena, aslan, athenex, boehringer ingelheim, bristol myers squibb, dermavant, ecor1, eli lilly, evommune, forte, galderma, incyte, janssen, landos, leo pharma, novartis, pfizer, rapt, regeneron, sanofi genzyme, sun pharma, ucb pharma, vibliome, and xencor. lsg: consultant for abbvie, amgen, arcutis, dermavant, leo pharma, bristol myers squibb, eli lilly, novartis, pfizer, sanofi-regeneron, and ucb pharma; principal investigator for abbvie, arcutis, dermavant, leo pharma, novartis, and ucb pharma. mg: investigator, speaker, consultant, or advisory board member for abbvie, amgen, akros, arcutis, bausch health, bristol myers squibb, boehringer ingelheim, celgene, dermavant, dermira, eli lilly, galderma, gsk, janssen, kyowa kirin, medimmune, merck, novartis, pfizer, regeneron, sanofi genzyme, sun pharmaceuticals, and ucb pharma. bs: consultant (honoraria): abbvie, almirall, amgen, arcutis, arena, aristea, asana, boehringer ingelheim, bristol myers squibb, connect biopharma, dermavant, eli lilly, epi health, evelo biosciences, immunic therapeutics, janssen, leo, maruho, meiji seika pharma, mindera health, novartis, ono, pfizer, regeneron, sanofi-genzyme, sun pharma, ucb pharma, union therapeutics, ventyxbio, and vtv therapeutics; stock options: connect biopharma, mindera health; speaker: abbvie, eli lilly, janssen, regeneron, and sanofi-genzyme; scientific co-director (consulting fee): corevitas (formerly corrona) psoriasis registry; investigator: abbvie, cara, corevitas psoriasis registry, dermavant, dermira, and novartis; editor-in-chief (honorarium): journal of psoriasis and psoriatic arthritis. ap: investigator and/or speaker and/or advisor for abbvie, almirall, amgen, biogen, boehringer ingelheim, celgene, eli lilly, galderma, gsk, hexal, janssen, leo pharma, mc2, medac, merck serono, mitsubishi pharma, msd, novartis, pfizer, regeneron, roche, sandoz, schering-plough, tigercat pharma, and ucb pharma. jmc: principal/senior investigator and/or consultant and/or advisor for abbvie, amgen, biogen, bristol myers squibb, celgene, eli lilly, janssen, leo pharma, novartis, sandoz, and ucb pharma. pg: consultant for abbvie, abiogen, almirall, celgene, eli lilly, janssen, leo pharma, merck, msd, novartis, otsuka, pfizer, pierre fabre, sanofi, and ucb pharma. jb: veramed statistical consultant for ucb pharma. cm, dd: employees and shareholders of ucb pharma. nng: former employee and shareholder of ucb pharma. rbw: consulting fees from abbvie, almirall, amgen, arena, astellas, avillion, biogen, bristol myers squibb, boehringer ingelheim, celgene, eli lilly, gsk, janssen, leo pharma, novartis, pfizer, sanofi, and ucb pharma; research grants to his institution from abbvie, almirall, janssen, leo pharma, novartis, and ucb pharma; honoraria from astellas, dice, gsk, and union. acknowledgements: these studies were funded by ucb pharma. we thank the patients and their caregivers in addition to the investigators and their teams who contributed to these studies. the authors acknowledge susanne wiegratz, msc, ucb pharma, monheim, germany for publication coordination, poppy wilson, mbiol, costello medical, london, uk for medical writing and editorial assistance and the design team at costello medical for graphic design assistance. all costs associated with development of this poster were funded by ucb pharma. rbw is supported by the nihr manchester biomedical centre. figure 1 study design figure 2 efficacy responses for moderate psoriasis patients through two years (mnri, nri, oc) aes: adverse events; bkz: bimekizumab; bmi: body mass index; bsa: body surface area; dlqi: dermatology life quality index; eair: exposure-adjusted incidence rate; ibd: inflammatory bowel disease; iga: investigators global assessment; il: interleukin; mace: major adverse cardiac events; mnri: modified non-responder imputation; nri: non-responder imputation; oc: observed case; ole: open-label extension; pasi 75/90/100: ≥75%/≥90%/100% improvement from baseline in the psoriasis area and severity index; q4w: every 4 weeks; q8w: every 8 weeks; sd: standard deviation; sib: suicidal ideation and behavior; teae: treatment-emergent adverse event; tnf: tumour necrosis factor. table 1 baseline characteristics table 2 summary of teaes in moderate psoriasis patients table 3 incidence rates of teaes by time period a) pasi ≤2 b) pasi 100 c) bsa ≤1 aanalyses include patients who received open-label escape treatment (bkz 320 mg q4w) in be ready;2 bpatients who achieved ≥pasi 90 at the end of the feeder studies were randomized 4:1 in be bright and 1:1 in be radiant to bkz 320 mg q4w or q8w; cweek numbers correspond to feeder study baseline; ole week 48 (two years) corresponds to be radiant week 96, be vivid/be bright week 100, and be ready/be bright and be sure/be bright week 104; din be bright, at ole week 24, patients achieving ≥pasi 90 could switch to q8w at the investigator’s discretion; in be radiant, at ole week 16 or the next scheduled clinic visit, patients switched to bkz q8w after the implementation of a protocol amendment. adata are reported for all bkz-treated patients with moderate psoriasis, regardless of dosing regimen; bdata are reported for all patients with moderate to severe psoriasis, randomized to bkz at baseline of the be sure, be vivid, be ready, and be radiant phase 3/3b trials who entered the oles; cvalues in bold are for assessments used to distinguish between moderate and moderate to severe psoriasis. teaes were assigned to the dose most recently received prior to the teae’s date of onset. patients who received both bkz 320 mg q4w and q8w at different times in the trials were included in the population count of both groups, but only once in the bkz total group. be radiant data cut-off was 20 april 2021; be bright data cut-off was 09 nov 2020. adata reported for all patients with moderate psoriasis who received ≥1 bkz dose; bproportion of patients reporting at least one teae in that category; cno deaths were assessed as treatment-related. data are reported for all patients with moderate psoriasis who received ≥1 bkz dose (bkz total). for patients in the be ready escape arm who then entered be bright, their oc assessments were used for oc only, whilst an nri record which was created at the same visit, even if an oc assessment was present, was used for nri. anumber of patients who entered the oles; bbe sure, be vivid, and be ready extended beyond 48 weeks; week 48 was the last common timepoint; cole week 48 (two years) corresponds to be radiant week 96, be vivid/be bright week 100, and be ready/be bright and be sure/be bright week 104. moderate psoriasis bkz totala n=301 moderate to severe psoriasis bkz-randomizedb n=1,208 age (years), mean ± sd 46.3 ± 14.3 45.4 ± 13.8 male, n (%) 205 (68.1) 844 (69.9) caucasian, n (%) 271 (90.0) 1,053 (87.2) weight (kg), mean ± sd 87.9 ± 19.6 89.7 ± 22.0 bmi, mean ± sd 29.3 ± 6.1 29.9 ± 6.8 duration of psoriasis (years), mean ± sd 17.7 ± 13.4 18.3 ± 12.7 pasi, mean ± sdc 15.7 ± 2.9 20.7 ± 7.5 bsa (%), mean ± sdc 12.9 ± 1.6 26.2 ± 15.6 iga, n (%)c 3: moderate 301 (100) 793 (65.6) 4: severe 0.0 412 (34.1) dlqi, mean ± sd 10.6 ± 6.3 10.6 ± 6.5 any prior systemic therapy, n (%) 214 (71.1) 933 (77.2) prior biologic therapy, n (%) 113 (37.5) 453 (37.5) anti-tnf 51 (16.9) 187 (15.5) anti-il-17 53 (17.6) 241 (20.0) anti-il-23 20 (6.6) 64 (5.3) anti-il-12/23 19 (6.3) 72 (6.0) bkz total patientsa n=539 bkz q8w patients n=395 bkz q4w patients n=499 eair (95% ci) n (%)b eair (95% ci) n (%)b eair (95% ci) n (%)b any teae 224.0 (204.6, 244.7) 489 (90.7) 164.8 (144.9, 186.7) 247 (62.5) 258.1 (233.8, 284.2) 412 (82.6) serious teaes 7.6 (5.9, 9.6) 67 (12.4) 7.9 (5.4, 11.3) 30 (7.6) 7.3 (5.2, 10.0) 38 (7.6) discontinuation due to teaes 3.4 (2.3, 4.8) 31 (5.8) 2.8 (1.4, 5.1) 11 (2.8) 3.7 (2.3, 5.8) 20 (4.0) severe teaes 6.6 (5.0, 8.5) 59 (10.9) 7.1 (4.7, 10.3) 27 (6.8) 6.7 (4.7, 9.3) 35 (7.0) deathsc 0.3 (0.1, 0.9) 3 (0.6) 0.3 (0.0, 1.4) 1 (0.3) 0.4 (0.0, 1.3) 2 (0.4) most common teaes nasopharyngitis 21.2 (17.9, 24.8) 154 (28.6) 20.0 (15.4, 25.6) 64 (16.2) 24.4 (20.0, 29.4) 108 (21.6) oral candidiasis 13.3 (10.9, 16.1) 106 (19.7) 11.8 (8.5, 16.0) 42 (10.6) 17.6 (14.0, 21.9) 83 (16.6) upper respiratory tract infection 7.8 (6.1, 10.0) 66 (12.2) 8.0 (5.3, 11.4) 29 (7.3) 8.4 (6.1, 11.4) 42 (8.4) safety topics of interest serious infections 1.5 (0.8, 2.6) 14 (2.6) 1.0 (0.3, 2.6) 4 (1.0) 2.1 (1.0, 3.7) 11 (2.2) ibd 0.1 (0.0, 0.6) 1 (0.2) 0.0 0.0 0.2 (0.0, 1.0) 1 (0.2) adjudicated sib 0.0 0.0 0.0 0.0 0.0 0.0 malignancies 1.1 (0.5, 2.0) 10 (1.9) 0.8 (0.2, 2.2) 3 (0.8) 1.3 (0.5, 2.7) 7 (1.4) serious hypersensitivity reactions 0.1 (0.0, 0.6) 1 (0.2) 0.3 (0.0, 1.4) 1 (0.3) 0.0 0.0 adjudicated mace 0.3 (0.1, 0.9) 3 (0.6) 0.5 (0.1, 1.9) 2 (0.5) 0.2 (0.0, 1.0) 1 (0.2) elevated liver enzymes 2.7 (1.7, 3.9) 24 (4.5) 2.9 (1.4, 5.1) 11 (2.8) 2.8 (1.6, 4.7) 15 (3.0) eair (95% ci) weeks 0–16 n=539 weeks 16–52 n=525 weeks 52–104 n=443 any teae 339.7 (304.3, 378.2) 226.7 (204.3, 251.0) 170.6 (151.1, 192.0) serious teaes 7.9 (4.2, 13.6) 7.3 (4.7, 10.9) 8.2 (5.4, 12.0) discontinuation due to teaes 4.3 (1.7, 8.8) 3.6 (1.9, 6.3) 3.4 (1.7, 6.1) severe teaes 5.5 (2.5, 10.4) 7.7 (5.0, 11.3) 8.2 (5.3, 12.0) deaths 0.6 (0.0, 3.4) 0.3 (0.0, 1.7) 0.3 (0.0, 1.7) most common teaes nasopharyngitis 34.0 (25.4, 44.4) 27.6 (22.0, 34.2) 21.0 (16.1, 27.0) oral candidiasis 31.6 (23.5, 41.7) 19.1 (14.5, 24.6) 12.2 (8.6, 16.8) upper respiratory tract infection 10.5 (6.1, 16.7) 12.0 (8.5, 16.5) 6.7 (4.2, 10.2) percentage of patients achieving pasi outcomes at week 16 and ole week 48 (mnri) a high proportion of patients with moderate psoriasis achieved pasi 100 at week 16 and through to two years (ole week 48) suggesting that high levels of improvement can be observed regardless of disease severity. p ro p o rt io n o f p a ti e n ts a c h ie v in g p a s i o u tc o m e s (% ) 80 60 40 20 0 100 pasi ≤2 week 16 ole week 48 pasi 100 pasi ≤2pasi 100 66.1 77.7 91.4 95.4 mnri; n=301 mnri; n=269 be sure, be vivid, be readya and be radiant1–4 (pooled, double-blinded) be bright5 and be radiant (open-label extension) maintenance period open-label treatment periodinitial treatment period bkz 320 mg q4w n=301 moderate psoriasis patients bkz 320 mg q4w bkz 320 mg q4w bkz 320 mg q4w week 48 week 52/56c be radiant be bright week 16 response assessment ole week 0b week 64 week 76/80c ole week 16/24d week 96 week 100/104c ole week 48 bkz 320 mg q8w <pasi 90 <pasi 90 ≥pasi 90 ≥pasi 90 bkz 320 mg q8w bkz 320 mg q8w 4:1 be bright 1:1 be radiant 0 8 16 24 32 40 48b 8 16 24 32 40 48c week ole week double-blinded treatment open-label extension 100 80 60 40 20 0 p a s i ≤ 2 r e sp o n se r a te ( % ) 91.3 (273/299) 91.4 90.7 97.3 (254/261) 96.7 (237/245) 91.7 95.4 84.4 84.0 n=301 n=269a mnri nri oc 0 8 16 24 32 40 48b 8 16 24 32 40 48c week ole week double-blinded treatment open-label extension 100 80 60 40 20 0 p a s i 1 0 0 r e sp o n se r a te ( % ) 66.2 (198/299) 66.1 65.8 82.0 (214/261) 82.0 (201/245) 74.6 77.7 71.1 71.7 0 8 16 24 32 40 48b 8 16 24 32 40 48c week ole week double-blinded treatment open-label extension 100 80 60 40 20 0 b s a ≤ 1 r e sp o n se r a te ( % ) 80.9 (241/298) 93.1 (243/261) 93.5 (229/245) 80.8 87.280.1 80.7 91.5 81.4 skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 410 brief article erythema elevatum diutinum associated with tuberculosis christopher j. mancuso, do, mhs1, gerard danosos, do1, tyler ruppel, do2, graham h. litchman, do, ms1, sourab choudhury, do1,3,4 1department of dermatology, st. john’s episcopal hospital, new york, ny 2department of dermatology, broward health north, fort lauderdale, fl 3department of dermatology, icahn school of medicine at mount sinai, new york, ny 4department of dermatology, st. barnabas hospital, new york, ny erythema elevatum diutinum (eed) is a rare skin disease most commonly presenting as red or brown papules, plaques, and nodules on extensor surfaces.1 eed was first described in 1888 by hutchinson and later named by radcliff-crocker and williams in 1894.2 lesions are typically asymptomatic, but pain, pruritis, or arthralgias may be present.3 adults between the fourth and sixth decades of life are frequently affected with no known sex or racial predilection.4 eed is a small-vessel leukocytoclastic vasculitis that progresses to perivascular fibrosis.5 it is thought to be caused by immune complex deposition in small vessels resulting in an inflammatory response.3 it is a chronic, relapsing disease that has most commonly been associated with hiv and gammaglobulinemias, as well as streptococcal infection, hiv, tuberculosis, rheumatoid arthritis, and celiac disease.1,3 the differential diagnosis of eed may include sweet’s syndrome, granuloma annulare, kaposi sarcoma, and bacillary angiomatosis; and thus, histologic correlation is imperative for diagnosis.1 oral dapsone is the current treatment of choice while other therapies including colchicine, steroids, antibiotics, and surgery have also been used.1 we report a rare case of eed associated with underlying tuberculosis infection. a 45-year-old african american female with a past medical history of hypertension and type-2-diabetes presented to our clinic in the fall of 2021 with itchy papules on her legs and ankles for 6 months. she reported that abstract erythema elevatum diutinum (eed) is a rare small vessel vasculitis with cutaneous manifestations most commonly presenting as red or brown papules, plaques, and nodules on extensor surfaces. it is a chronic, relapsing disease that is often associated with states of immunocompromise, e.g., hiv, gammaglobulinemias, and, more rarely, tuberculosis. currently oral dapsone is the current treatment of choice, and while most patients respond well, it is imperative that the diagnosis be made early. we report a rare case of eed associated with underlying tuberculosis infection. recognizing the distinct manifestations of eed and understanding its immunologic and infectious disease associations may enable clinicians to properly recognize, manage, and treat patients with eed. introduction case report skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 411 she had tried petrolatum ointment and overthe-counter hydrocortisone without improvement. she reported having pet cats for several years and denied any sick contacts or recent illness. the patient also denied any bug bites, history of hiking, or possible exposure to plants. of note, she reported that she recently traveled to the dominican republic and had immigrated from haiti four years prior. on examination, scattered hyperpigmentedto-erythematous nummular macules and papules were present on her lower legs and ankles with large, flesh-colored nodules on her lateral feet. a punch biopsy was performed, which demonstrated an interstitial granulomatous infiltrate, admixed neutrophils and lymphocytes in the reticular dermis, and a leukocytoclastic small vessel vasculitis with perivascular onion-skinning fibrosis. in addition, of the laboratory tests ordered, a positive quantiferon gold was significant. based on these findings, eed with underlying tuberculosis (tb) was diagnosed. the patient was treated with oral dapsone and symptomatic management with clobetasol 0.05% ointment and referred to infectious disease for treatment of tb. figure 1. nodules on left lateral foot figure 2. nodules, macules, and papules seen on left lower extremity skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 412 figure 3. close up visualization of macules and papules on left lower extremity eed is a rare, chronic cutaneous leukocytoclastic vasculitis of small vessels that presents as red-brown soft papules that progress to firm nodules due to perivascular fibrosis.6 only several hundred cases of eed have been described in the literature.7 while an association between eed and other diseases such as hiv, tb, paraproteinemias, and malignancy is often described, very few cases of eed associated with tb are reported, especially when compared to the other associated diseases.3 in their review of 133 cases published from 1990 to 2014, doktor et al3 found just two cases of eed associated with tb. the pathogenesis of eed is not fully understood but is most likely due to the deposition of immune complexes in small blood vessels leading to an inflammatory reaction. the underlying etiology is thought to be related to high circulating antibody levels produced after recurrent infections.3 classically, streptococcal infection and rheumatoid disease have been cited as causes for these immune-complex formations.8 however, as mentioned previously, reports have shown eed to be associated with autoimmune diseases such as ulcerative colitis, crohn’s disease, relapsing polychondritis, diabetes mellitus, celiac disease, and pyoderma gangrenosum; as well as infectious diseases including hiv, hepatitis, syphilis, and tuberculosis. tuberculosis is caused by mycobacterium tuberculosis and is responsible for up to two million deaths each year.9 tb is a multisystem disease affecting various organ systems including the musculoskeletal system, skin, and nervous system, but is most notable for its effects on the lungs. common symptoms include cough, hemoptysis, weight loss, fever, and night sweats. tb is typically spread person-toperson via inhalation of aerosol droplets.10 an infected individual first develops primary tuberculosis in which the bacteria localize to the lungs and form a gohn focus, which typically then enters a state of latency, known as latent tuberculosis. latent tuberculosis may be reactivated during a state of immunosuppression. primary progressive tuberculosis occurs when individuals develop active disease following first exposure to tb and is seen in immunocompromised hosts. typically, however, most people develop secondary tuberculosis several years after the initial primary infection due to reactivation.11 discussion skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 413 m. tuberculosis is an acid-fast, non-motile, obligate-aerobic, non-spore forming, catalase-negative, intracellular bacillus that is neither gram-positive or gram-negative.11 tb is a type-iv delayed hypersensitivity reaction stimulating cd4+ t lymphocytes, which recruit and activate macrophages. cytokines interferon-gamma, interleulin-4, interleukin-6, and tumor-necrotic-factoralpha play a major role in the pathogenesis of tb. tb is notable for its formation of granulomas, defined as aggregations of macrophages fused together to form giant cells, which are subsequently surrounded by lymphocytes.9 screening tests for tb include the ppd skin test and interferon release assay. confirmatory tests include chest x-ray, acid-fast staining, culture, and nuclear amplification tests. first-line treatment for tb includes rifampin, isoniazid, pyrazinamide, and ethambutol. 10 the prognosis for eed patients varies based upon the underlying disorder.8 proper and timely treatment of the underlying cause or infection should significantly improve eed lesions. of note, patients with eed are not at increased risk for developing systemic vasculitis. moreover, most patients with tb have a favorable outcome due to adequate treatment. without treatment, however, there is a 50% mortality rate for tuberculosis. patients at risk for worse outcomes include the very young and elderly, as well as factors of delayed treatment, severe respiratory compromise, immunosuppression, and multi-drug resistance. these patients may experience prolonged eed as well as lung damage and associated conditions, dissemination of disease, and systemic amyloidosis, among others.11 this case demonstrates an exceedingly rare presentation of erythema elevatum diutinum caused by tuberculosis in a middle-aged woman. with only several hundred cases of reported eed, we hope to raise awareness of this rare disease process associated with tb so dermatologists may properly identify and manage eed in an uncommon clinical setting. practitioners should have a high index of suspicion for individuals presenting with reddish-brown papules and plaques on extensor surfaces, especially during the fourth through sixth decades of life. recognizing the distinct manifestations of eed and understanding its immunologic and infectious disease associations may enable clinicians to properly recognize, manage, and treat patients with eed. conflict of interest disclosures: none funding: none corresponding author: christopher j mancuso, do, mhs department of dermatology st. john’s episcopal hospital far rockaway, ny 11691 email: cjmancuso@gmail.com references: 1. momen se, jorizzo j, al-niaimi f. erythema elevatum diutinum: a review of presentation and treatment. j eur acad dermatol venereol. 2014;28(12):1594-1602. doi:10.1111/jdv.12566 2. haber h. erythema elevatum diutinum. br j dermatol. 1955;67(4):121-145. doi:10.1111/j.1365-2133.1955.tb12706.x 3. doktor v, hadi a, hadi a, phelps r, goodheart h. erythema elevatum diutinum: a case report and review of literature. int j dermatol. 2019;58(4):408-415. doi:10.1111/ijd.14169 4. high wa, hoang mp, stevens k, cockerell cj. late-stage nodular erythema elevatum diutinum. j am acad dermatol. 2003;49(4):764-767. doi:10.1067/s0190-9622(03)01834-6 5. leboit pe, benedict yen ts, wintroub b. the evolution of lesions in erythema elevatum diutinum: am j dermatopathol. 1986;8(5):392402. doi:10.1097/00000372-198610000-00005 conclusion skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 414 6. logan s, sontheimer r. concurrence of erythema elevatum diutinum and hiv infection: a case report and literature review. jaad case rep. 2019;5(12):1093-1096. doi:10.1016/j.jdcr.2019.10.011 7. newburger j, schmieder gj. erythema elevatum diutinum. in: statpearls. statpearls publishing; 2022. accessed january 31, 2022. http://www.ncbi.nlm.nih.gov/books/nbk448069/ 8. gibson le, el-azhary ra. erythema elevatum diutinum. clin dermatol. 2000;18(3):295-299. doi:10.1016/s0738-081x(99)00120-0 9. smith i. mycobacterium tuberculosis pathogenesis and molecular determinants of virulence. clin microbiol rev. 2003;16(3):463496. doi:10.1128/cmr.16.3.463-496.2003 10. parmer j, allen l, walton w. ce: tuberculosis: a new screening recommendation and an expanded approach to elimination in the united states. am j nurs. 2017;117(8):24-34. doi:10.1097/01.naj.0000521946.45448.90 11. adigun r, singh r. tuberculosis. in: statpearls. statpearls publishing; 2022. accessed january 31, 2022. http://www.ncbi.nlm.nih.gov/books/nbk441916/ powerpoint presentation • the mean dermatology life quality index (dlqi) improvement from baseline to week 8 was significantly greater for cal/bdp pad-cream (6.5 points) compared to cal/bdp gel/ts (5.6 points) (p<0.0001) (figure 3). a dlqi between 0 and 1 (no or little impact of disease on the patient’s life) at week 8 was obtained by 43.8% in the cal/bdp pad-cream group and 34.2% in the cal/bdp gel/ts group (p=0.0005). • cal/bdp pad-cream treatment convenience, as measured by the ptcs (table 2) was higher than for cal/bdp gel/ts at all studied time points, and significantly higher for all individual questions at week 8 compared to cal/bdp gel/ts (fig. 4). • cal/bdp pad-cream was well tolerated with no adverse drug reactions with a frequency above 1%. • overall, 1271 patients were included in this analysis, 551 patients were in the cal/bdp pad-cream group, 542 patients were in the cal/bdp gel/ts group, and 178 patients were in the pad-cream vehicle group. overall, demographic and baseline characteristics were comparable between the three treatment groups (table 1). • the proportion of patients achieving pga treatment success (at least 2-step improvement to clear or almost clear) at week 8 was statistically significantly higher in the cal/bdp pad-cream group (43.2%) compared to the cal/bdp gel/ts group (31.9%) (p<0.0001). moreover, a statistically significant difference in pga between cal/bdp pad-cream and cal/bdp gel/ts was observed as early as week 4 (p=0.0001) (figure 1). results linda stein gold1, andreas pinter2, matthias augustin3 1dermatology clinical research, henry ford health system, detroit, michigan, usa; 2dept. of dermatology, venereology and allergology, university hospital frankfurt/main, frankfurt/main, germany; 3university medical center hamburg-eppendorf, hamburg, germany efficacy and safety of calcipotriene/betamethasone dipropionate cream for the treatment of plaque psoriasis evaluated from pooled phase 3 data • the fixed dose combination of calcipotriene (cal 0.005% w/w, 50 µg/g) and betamethasone dipropionate (bdp 0.064% w/w, 0.5 mg/g as betamethasone) is a well-established treatment option for psoriasis based on strong scientific rationale for the single agents having complementary efficacy and safety. • cal/bdp pad-cream is an easily spreadable cream based on pad technology™, an innovative formulation and drug delivery system1. introduction • writing support was provided by anja snel-prentø, medlink. • the trials were funded by mc2 therapeutics. • pga, physician global assessment. mpasi, modified psoriasis area and severity index. dlqi, dermatology life quality index. bdp, betamethasone dipropionate. cal, calcipotriene. ptcs, psoriasis treatment convenience scale. sd, standard deviation. ts, topical suspension. acknowledgements & abbreviations conclusions • in an exploratory post-hoc statistical analysis of the pooled phase 3 data, cal/bdp pad-cream showed significantly greater efficacy than cal/bdp gel/ts. patientreported outcomes demonstrate that cal/bdp pad-cream generally offers greater patient satisfaction when compared to cal/bdp gel/ts. methods • cal/bdp pad-cream was evaluated in two phase 3, multicentre, randomized, investigator-blinded, parallel-group trials (nct03802344 and nct03308799) comparing the efficacy of cal/bdp pad-cream with cal/bdp gel/topical suspension (ts) and pad-cream vehicle. adult patients with mild-moderate psoriasis according to the physician global assessment (pga) were enrolled and applied trial medication once daily for up to 8 weeks. • the primary endpoint in the us trial (nct03308799) was the proportion of subjects who achieved minimum 2-points improvement in pga to clear or almost clear disease from baseline to week 8. the primary endpoint of the eu trial (nct03802344) was the percentage change in modified psoriasis area and severity index (mpasi) from baseline to week 8. • the two phase 3 trials each evaluated superiority of cal/bdp pad-cream versus pad-cream vehicle, and non-inferiority versus cal/bdp gel/ts. • the statistical analysis of pooled phase 3 data presented herein was performed as an exploratory, post-hoc analysis to evaluate statistical differences between cal/bdp pad-cream and cal/bdp gel/ts based on a modified intention-to-treat population (n=1271) having at least one assessment of pga after baseline. multiple imputation for missing data was applied for endpoints, except for psoriasis treatment convenience scale (ptcs) for which missing data was imputed using a last observation carried forward approach. figure 1. pga treatment success figure 2. mpasi, percentage change from baseline • the mean percentage reduction in mpasi from baseline to week 8 was significantly greater for cal/bdp pad-cream (64.6%) than cal/bdp gel/ts (56.4%) (p<0.0001). the difference in mpasi treatment effect between cal/bdp pad-cream and cal/bdp gel/ts was statistically significant as early as week 1 (p=0.0009) (figure 2). 1praestegaard m, steele f, crutchley n. polyaphron dispersion technology, a novel topical formulation and delivery system combining drug penetration, local tolerability and convenience of application. dermatol ther (heidelb). 2022 oct;12(10):2217-2231. references figure 3. mean dlqi improvement 2023 winter clinical miami *: p<0.05; **: p<0.01; ***: p<0.001; ****: p<0.0001; cal/bdp pad-cream vs. cal/bdp gel/ts cal/bdp pad-cream (n=551) cal/bdp gel/ts (n=542) pad-cream vehicle (n=178) mean age, years (sd) 50.9 (14.1) 52.2 (14.2) 50.6 (13.8) male, n (%) 337 (61.2) 333 (61.4) 113 (63.5) mean pga (sd) 2.8 (0.4) 2.8 (0.4) 2.8 (0.4) mean mpasi (sd) 7.5 (3.9) 7.8 (4.0) 7.6 (4.0) mean dlqi (sd) 9.6 (6.0) 9.9 (6.7) 9.3 (6.2) table 1. baseline demographics and characteristics 3,6 25,2 37,7 43,2 2,0 15,6 24,6 31,9 0,0 1,5 3,2 5,2 0 10 20 30 40 50 0 2 4 6 8 % p g a tr ea tm en t s uc ce ss weeks cal/bdp pad-cream cal/bdp gel/ts pad-cream vehicle**** **** **** 25,5 52,6 60,5 64,6 20,5 43,6 51,2 56,4 8,5 15,3 19,4 20,0 0 10 20 30 40 50 60 70 0 2 4 6 8 m pa si , % c ha ng e fr om b as el in e weeks cal/bdp pad-cream cal/bdp gel/ts pad-cream vehicle *** **** **** **** -3,7 -5,7 -6,5 -3,4 -5,0 -5,6 -1,8 -2,1 -2,5 -7 -5 -3 -1 0 2 4 6 8 d lq i i m pr ov em en t weeks *** **** p=0.0575 # ptcs questions 1 how easy was the treatment to apply to the skin? 2 how greasy was the treatment when applying it to the skin? 3 how moisturized did your skin feel after applying the treatment? 4 how greasy did your skin feel after applying the treatment? 5 how much did treating your skin disrupt your daily routine? 6 overall, how satisfied were you with the medical treatment? table 2. ptcs questions figure 4. ptcs at week 8 cal/bdp pad-cream cal/bdp gel/ts pad-cream vehicle 0 2 4 6 8 10 #1 #2 #3 #4 #5 #6 pt cs questions cal/bdp pad-cream cal/bdp gel/ts **** ******** *** ** * dias nummer 1 powerpoint presentation objective association of insurance coverage with diagnosis of malignant melanoma before and after the affordable care act: a national database study • the surveillance, epidemiology, and end results (seer) cancer registry was analyzed for malignant melanoma between 2007 and 2015. • standardized mean difference (2007-2013 vs 2014-2015) was used to compare insurance trends with sub-analysis for medicaid expansion/non-expansion states • survival was assessed via adjusted cox regression models. synopsis methods • to examine the impact of the aca on insurance type (uninsured, medicaid, non-medicaid) and trends among patients diagnosed with malignant melanoma • to assess survival outcomes in patients diagnosed with malignant melanoma by insurance type conclusion results • the aca was intended, in part, to reduce the uninsured population • the aca was fully implemented in 2014 with optional state medicaid expansion and health insurance marketplaces • prior studies show that insurance status affects cancer care, including prevention, diagnosis, stage at diagnosis, and management1 • the impact of the aca on insurance trends of patients diagnosed with malignant melanoma is unknown • nationally, the aca decreased percentage of uninsured patients (-1.12% to -2.26%, p<0.05) and increased percentage of medicaid enrollees (+1.53% to +4.02%, p<.005) diagnosed with malignant melanoma • expansion states showed decreased percentage of uninsured patients (-1.43% to -2.24%, p<0.05) and increased percentage of medicaid enrollees (+1.66% to +4.84%, p<0.05) • non-expansion states showed no change in percentages of uninsured patients and medicaid enrollees • all-cause and cause-specific mortality were decreased in uninsured and medicaid patients diagnosed with melanoma compared to non-medicaid insured patients (reference group). • the aca decreased the rate of patients diagnosed with malignant melanoma with uninsured status, but this was only significant in medicaid expansion states • however, medicaid patients have worse all-cause and cause-specific mortality compared to non-medicaid counterparts • we must address socioeconomic factors likely contributing these disparities through policy to ensure insurance coverage translates to quality care and survivorship references 1. ward e, halpern m, schrag n, cokkinides v, desantis c, bandi p, siegel r, stewart a, jemal a. association of insurance with cancer care utilization and outcomes. ca cancer j clin. 2008 jan-feb;58(1):9-31. vignesh ramachandran, md1, talha ayaz, md2, asad loya, md3 1 department of dermatology, new york university, new york, ny 2 department of radiology, university of texas medical branch, galveston, tx 3 department of ophthalmology, baylor college of medicine, houston, tx figures 1, 2, 3: (1) national insurance trends in patients diagnosed with malignant melanoma; (2) sub-analysis of insurance trends in states which expanded medicaid; (3) sub-analysis of insurance trends in non-expansion states 0 20 40 60 80 100 2007 2008 2009 2010 2011 2012 2013 2014 2015 in s u ra n c e r a te , % year of diagnosis figure 2. rates of insurance type in expansion states uninsured any medicaid non-medicaid insurance 0 20 40 60 80 100 2007 2008 2009 2010 2011 2012 2013 2014 2015 in s u ra n c e r a te , % year of diagnosis figure 1. rates of insurance type in all states uninsured any medicaid non-medicaid insurance 0 20 40 60 80 100 2007 2008 2009 2010 2011 2012 2013 2014 2015 in s u ra n c e r a te , % year of diagnosis figure 3. rates of insurance type in non-expansion states uninsured any medicaid non-medicaid insurance figures 4, 5: (4) overall (all-cause) survival by insurance type and (2) cause-specific (melanoma-specific) survival by insurance type all authors have no financial conflicts of interest or disclosures skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 156 brief articles dermatitis artefacta resembling pyoderma gangrenosum: a case report mary michael1, andrew newman do2, jason barr do2, travis lam md2 1lake erie college of osteopathic medicine, bradenton, fl 2honor health dermatology residency, scottsdale, az a leg ulcer is a physical finding that can result from multiple etiologies; accordingly, determination of the cause is essential for selecting appropriate treatment and need for further evaluation. the most common causes of leg ulcers are venous insufficiency, arterial insufficiency, and neuropathic disease. less common causes include physical injury, infection, vasculopathy, panniculitis, malignancy, medications, brown-recluse spider envenomation, and pyoderma gangrenosum (pg).1 pg is a poorly understood, noninfectious, neutrophilic dermatosis that presents as recurrent skin ulcers, most commonly on the lower extremity.2 the initial lesion starts as a tender pustule, progressing to a necrotic bulla that ulcerates with purulent drainage.2 approximately half of patients that develop pg present with a chronic underlying systemic inflammatory or malignant disease such as ulcerative colitis, rheumatoid arthritis, chronic active hepatitis, crohn’s disease, iga monoclonal gammopathy, and hematologic malignancies.2-4 ulcers can also be due to self-mutilation from an underlying psychological condition known as dermatitis artefacta (da). this diagnosis may be difficult to elucidate since it masquerades as other more common conditions. introduction dermatitis artefacta (da) is a self-inflicted skin condition that clinically mimics other dermatologic conditions. the etiology is multifactorial and is linked to underlying psychological conditions or psychosocial stressors with relief from automutilation. lesions present with variable morphology depending on the type of self-harm and therefore, is a diagnosis of exclusion. we present a case of lesions that initially appeared to be pyoderma gangrenosum (pg) due to a presentation of nonspecific ulcers on the lower extremity and a patient-reported history of inflammatory bowel disease (ibd). the patient, a retired nurse, carried out an exceptionally active role in deceiving the medical team. she fabricated her medical history, including a prior diagnosis of ibd, to help support her assertion that her skin lesions were pg. skin lesions that do not fit a particular clinical-pathological diagnosis and resist conventional treatments should prompt clinicians to consider a diagnosis of da. this case highlights the challenge of recognizing da, especially in medically-knowledgeable patients proficient with navigating the healthcare system. once other dermatologic conditions are ruled out, it is important to consider da since early intervention is necessary for good patient outcomes. abstract skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 157 a middle-aged female whom is a retired nurse presents with several large ulcers on the lower legs and left arm. these lesions started over four months prior to presentation. she asserts that she had been diagnosed with inflammatory bowel disease by a gastroenterologist, however, this was not corroborated by the medical team. on physical exam, large annular ulcerations were seen over the left arm and the bilateral lower legs. the most prominent lesions were noted on the left lower extremity (figure 1 and figure 2). venous and arterial doppler revealed good blood flow. the patient was admitted to the hospital floor for non-healing ulcers with a clinical suspicion for pyoderma gangrenosum. she was managed by a multidisciplinary team consisting of specialists in rheumatology, dermatology, and internal medicine. two punch biopsies were performed on the lesions revealing a dense superficial mixed cell infiltrate including neutrophils, histiocytes, lymphocytes, and eosinophils around a significant bed of ulceration. no sign of malignancy on histology was noted. direct immunofluorescence studies were negative. a gram stain was insignificant and cultures were insignificant, showing only mixed normal skin flora. specific cultures for fungus and mycobacteria were negative, including cultures for fungal and mycobacterial organisms. abundant eosinophils noted on histopathology is a feature not typical for pg, a condition defined by an abundance of neutrophils. a self-inflicted skin disorder was then suspected. accordingly, a sitter was asked to watch the patient around-the-clock. ten days after initiating the sitter, her skin improved significantly. the patient’s son incidentally found a labelled bottle of sodium hydroxide plus several vials of suspicious unlabeled powders in her belongings at the bedside. the medical team was convinced that her skin disease was purely self-inflicted. this case of initially-suspected pg was concluded to be da. figure 1. ulcers present over the left lower extremity. figure 2. ulcer on the dorsum of the left foot clearly reveals muscle tendons. case report skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 158 pg is a diagnosis of exclusion since the clinical, histopathologic, and laboratory findings are nonspecific.5 on physical exam, the ulcer of pg will be tender, necrotic, with irregular violaceous borders. a biopsy will demonstrate a neutrophilic infiltrate but be negative for microorganisms. additional investigations to rule out other causes of ulcers include venous and arterial function studies, anca, a coagulation panel including antiphospholipid antibody screening, and serum protein immunoelectrophoresis to test for monoclonal gammopathy. the diagnosis of pg is strengthened by a history of ibd or other systemic conditions. dermatitis artefacta, similar to pg, may present with ulcers and it remains a diagnosis of exclusion.4 in da, self-inflicted skin lesions result from the patient’s attempt to satisfy an internal psychological need, often a need to be cared for. the case herein showcases an exceptionally sophisticated attempt to deceive the medical team. she wounded her skin with harsh chemicals while fabricating an elegant medical rationale for her disease: pg associated with ibd. she apparently researched the clinical presentation of pg prior to her medical attention. those with a background in medicine, such as this case are often better at concealing the true nature of their disease. diagnosis of da is often challenging due to it having a multitude of clinical presentations combined with vague past medical histories that may or may not include a psychological history.6 clinicians must consider da when a dermatosis is atypical or unresponsive to conventional treatments, since a failure to recognize this condition early implies poor patient outcomes. other clues are lesions that improve with a sitter, a history of multiple hospital admissions and office visits, and prior professional medical training. importantly, clinicians should consider a referral to an appropriate psychiatric care specialist for adjunct therapy. conflict of interest disclosures: none funding: none corresponding author: mary michael, ms iv lake erie college of osteopathic medicine 5000 lakewood ranch blvd bradenton, fl 34211 usa phone: 727-389-8252 e-mail: marymichael94@gmail.com references: 1. singer aj, tassiopoulos a, kirsner rs. evaluation and management of lower-extremity ulcers. n engl j med 2017; vol 377:1559. 2. bennett ml, jackson jm, jorizzo jl, et al. pyoderma gangrenosum. a comparison of typical and atypical forms with an emphasis on time to remission. case review of 86 patients from 2 institutions. medicine (baltimore) 2000; 79:37. 3. von den driesch p. pyoderma gangrenosum: a report of 44 cases with follow-up. br j dermatol 1997; 137:1000. 4. binus am, qureshi aa, li vw, winterfield ls. pyoderma gangrenosum: a retrospective review of patient characteristics, comorbidities and therapy in 103 patients. br j dermatol 2011; vol 165:1244. 5. su wp, davis md, weenig rh, et al. pyoderma gangrenosum: clinicopathologic correlation and proposed diagnostic criteria. int j dermatol 2004; vol 43:790. 6. conde montero e, sanchez-albisua b, guisado s et al. factitious ulcer misdiagnosed as pyoderma gangrenosum. wounds. 2016. vol 28(2): 63-67. discussion mailto:marymichael94@gmail.com skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 649 original research willingness of patients from an urban safety-net dermatology clinic to receive a covid-19 vaccine hannah e. mumber, bs1*, daniela del campo, ba, bs1*, manuel alvarado, mph2,3, jacqueline watchmaker, md4 1 boston university school of medicine, boston, ma 2 division of pediatric neurology at boston medical center, boston, ma 3 boston university school of public health, boston, ma 4 southwest skin specialists, scottsdale, az *co-first authors a safe and effective vaccine against sarscov-2 is essential for a return to pre-covid “normalcy” both in the dermatology clinic and worldwide. recently, after extensive clinical trials, the food and drug administration (fda) has granted emergency use authorization to moderna, inc. and johnson & johnson and full approval to pfizer, inc., allowing vaccines to be brought to the u.s. market.1-3 while the development of these vaccines represents a monumental achievement that has helped to initiate the beginnings of a return to a precovid way of life, significant challenges remain regarding the public’s perception of the vaccines and the public’s willingness to receive the vaccines.4-6 currently, the u.s. population remains far from the herd immunity goal of 80%, and there has been abstract background: while recent vaccine development has initiated a return to pre-covid “normalcy” both in the dermatology clinic and worldwide, significant challenges remain regarding the public’s willingness to receive a covid-19 vaccine. dermatologists often discuss vaccinations with their patients and aid them in making evidence-based medical decisions. previous studies have looked at the u.s. population’s willingness to receive a covid-19 vaccine, but no studies have examined the dermatology patient population from an urban safety-net hospital. studies have shown that understanding the target audience is the first step towards increasing vaccine acceptance. methods: a cross-sectional, telephone-based survey study was administered to 326 patients of an urban safety-net hospital from july 2020 to august 2020 in order to assess willingness to obtain a covid-19 vaccine. results: our survey study showed that 57.7% of patients with a recent dermatology appointment are willing to receive a covid-19 vaccine and that safety concerns represent the main reason for patient hesitancy. patients who do not regularly receive a flu vaccine, non-caucasian patients, and those who know someone who tested positive for covid-19 are less willing to receive a covid-19 vaccine. patients with a recent dermatology appointment are more willing to receive a covid-19 vaccine than those who did not have a recent dermatology appointment. conclusions: our results provide dermatologists, especially those working in urban safety-net clinics, with key information about the attitude of patients toward the covid-19 vaccine. introduction skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 650 significant loss to follow-up for the second vaccination.7 in addition, given the lower levels of neutralizing antibody titers associated with newer strains, the need for boosters vaccines will keep covid-19 vaccinations at the forefront of healthcare maintenance and will require continued patient education.8 while preventative immunizations are often considered a cornerstone of the primary care encounter, vaccine discussion with patients is important across all specialties, including dermatology. dermatologists routinely discuss the need for yearly flu vaccines in immunocompromised patients, the need for the varicella zoster vaccine in older patients, and the need for adequate titers against hepatitis b prior to starting a biologic medication. at the present time, dermatologists are also discussing the covid-19 vaccine with their patients and encouraging skeptical patients to make evidence-based vaccination decisions. dermatologists have been shown to play a key role in recommending the covid-19 vaccine to their patients on immunosuppressive agents.9 previous studies have looked at the u.s. population’s willingness to receive a covid19 vaccine, but no studies have specifically looked at the dermatology patient population or patients from an urban safety-net hospital.4,5,10 studies have shown that understanding the target audience is the first step towards increasing vaccine acceptance, and therefore, the purpose of this study was to 1) determine what proportion of patients from an urban safetynet dermatology clinic are willing to receive a covid-19 vaccine, 2) determine which patient factors may correlate with an unwillingness of a patient to receive a covid-19 vaccine and 3) determine if there is a difference in attitude towards the covid-19 vaccine between patients who recently received dermatologic care and those who do not.11,12 after irb approval, a cross-sectional telephone survey study was conducted from june 2020 to july 2020. all patients were recruited from an urban safety-net hospital (boston medical center; boston, massachusetts). patients younger than 18 years old and non-english or spanishspeaking patients were excluded. a sample size calculation was performed prior to the study to ensure adequate power. two telephone lists were created from the electronic health record which represented the two patient cohorts: 1) a dermatology patient cohort consisting of patients with a recent (within 1 month) dermatology appointment and 2) a non-dermatology patient cohort consisting of internal medicine patients without a dermatology appointment in the last year. patients were called and asked to answer a telephone-based survey (table 1). table 1. survey questions 1. what is your highest level of education? 2. what race/ethnicity do you identify with? 3. do you regularly get the flu vaccine? 4. have you tested positive for covid-19? 5. have any of your close friends, relatives or colleagues tested positive for covid-19? 6. would you receive a covid-19 vaccine? 7. if you are unsure or unwilling to receive a covid-19 vaccine what is your main reason for concern? methods skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 651 patient demographic data were collected from the electronic health record and recorded along with the survey responses. participation in the survey was voluntary. univariate analysis was performed to describe relationships between patient willingness to receive a covid-19 vaccine and age, highest level of education, race/ethnicity, history of flu vaccination, and personal history or close friend/family member history of covid-19. multivariable chi-square analysis was performed to compare vaccination attitude between dermatology patients and non-dermatology patients. sas studio version 3.8 was used for statistical analysis. dermatology patient cohort 163 patients with a recent (within 1 month) dermatology appointment were surveyed. patient demographic information is provided in table 2. the majority of respondents (57.7%, n=94) stated they were willing to receive a covid-19 vaccine; 30.7% (n=50) stated they were unsure, and 11.7% (n=19) stated they were unwilling (table 3). concerns with vaccine safety represented the main reason patients were unsure or unwilling to receive a covid-19 vaccine (73.9%, n=51). among the patient factors analyzed, those who do not regularly receive a flu vaccine, those with family, friends, or colleagues who tested positive for covid19, and non-caucasian patients were less willing to receive a covid-19 vaccine. those who regularly received their flu vaccine had 4.64 (95% ci 1.66, 12.94) times the odds of being willing to receive the table 2. patient demographic data characteristic total sample (n=326) dermatology patient cohort (n=163) nondermatology patient cohort (n=163) sex female 249 (76.4%) 111 (68.1%) 138 (84.7%) male 77 (23.6%) 52 (31.9%) 25 (15.3%) mean age (standard deviation) 47.1 (16.9) 44.8 (17.0) 49.5 (16.5) self-identified race/ethnicity african american 114 (35.0%) 37 (22.7%) 77 (47.2%) asian 8 (2.5%) 6 (3.7%) 2 (1.2%) biracial 14 (4.3%) 5 (3.1%) 9 (5.5%) caucasian 91 (27.9%) 64 (39.3%) 27 (16.6%) hispanic/latino 69 (21.2%) 39 (23.9%) 30 (18.4%) other 23 (7.1%) 10 (6.1%) 13 (8.0%) not disclosed 7 (2.0%) 2 (1.2%) 5 (3.1%) highest level of education elementary 9 (2.8%) 1 (0.6%) 8 (4.9%) middle school 7 (2.1%) 7 (4.3%) 0 (0%) some high school 15 (4.6%) 6 (3.7%) 9 (5.5%) high school diploma 83 (25.5%) 43 (26.4%) 40 (24.5%) associate’s degree 20 (6.1%) 11 (6.7%) 9 (5.6%) bachelor’s degree 93 (28.6%) 41 (25.1%) 52 (31.9%) master’s degree 42 (12.9%) 22 (13.5%) 20 (12.3%) doctorate/professional school 6 (1.8%) 4 (2.5%) 2 (1.2%) other 7 (2.1%) 4 (2.5%) 3 (1.8%) not disclosed 6 (1.8%) 0 (%) 6 (3.7%) results skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 652 table 3. willingness to receive a covid-19 vaccine and reasons for hesitancy total sample (n=326) dermatolog y patient cohort (n=163) nondermatolo gy patient cohort (n=163) would you receive a covid-19 vaccine? yes 171 (52.5% ) 94 (57.7%) 77 (47.2%) no 61 (18.7% ) 19 (11.7%) 42 (25.8%) unsure 94 (28.3% ) 50 (30.7%) 44 (27.0%) what is your main reason for hesitancy or unwillingness to get a covid-19 vaccine? concern about safety 87 (56.1% ) 51 (73.9%) 36 (41.9%) concern about efficacy 7 (4.5%) 3 (4.3%) 4 (4.6%) against personal/religio us beliefs 7 (4.6%) 4 (5.8%) 3 (3.5%) already had covid-19, no need 1 (0.6%) 0 (0%) 1 (1.2%) other 35 (22.6% ) 10 (14.5%) 25 (29.1%) not disclosed 18 (11.6% ) 1 (1.5%) 17 (19.7%) covid-19 vaccine than those who do not regularly receive the flu vaccine (p=0.0020). those with close family, friends, or colleagues who tested positive for covid19 had 0.326 (95% ci 0.1188, 0.8954) times the odds of being willing to receive a covid-19 vaccine compared to those who did not (p=0.0252). non-caucasian patients had 0.272 times the odds of being willing to receive a covid-19 vaccine compared to caucasian participants (95% ci 0.0841, 0.8827, p=0.0202). there was no association between willingness to receive the covid-19 vaccine and age, level of education, or personal history of covid-19. combined data (dermatology and nondermatology patient cohorts) in total, 326 patients were surveyed (163 patients with a recent dermatology appointment and 163 patients without a recent dermatology appointment) with a mean age of 47.1 years (sd=16.9). overall, 52.5% (171/326) of patients stated they were willing to receive a covid-19 vaccine (47.2% in non-dermatology cohort; 57.7% in the dermatology cohort). those with a recent dermatology appointment had 2.69 (95%ci 1.4517, 5.0164) times the odds of being willing to receive the covid-19 vaccine compared to those without a recent dermatology appointment (p=0.0014). studies show patients are more willing to receive a vaccination if the vaccination is recommended by a healthcare provider.13 because of this, all healthcare providers, including dermatologists, play a key role in vaccine education. vaccine education is especially important today given the plethora of misinformation surrounding the covid-19 vaccine. even prior to the covid-19 pandemic however, dermatologists played an important role in vaccine education given that many dermatologic conditions require immunosuppressant medications and thus up to date vaccinations. additionally, given the frequent follow-up required for many skin conditions, dermatologists have the opportunity to routinely educate patients on important preventative health measures discussion skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 653 such as the need for vaccinations. given dermatologists often engage in vaccine discussion, it is important for us to understand the overall attitude of our patient population towards vaccines, including the covid-19 vaccine. therefore, our study investigated the attitudes of dermatology patients in an urban safety-net hospital toward covid-19 vaccines and determined which patient factors were associated with an increased or decreased willingness to receive the vaccine. once armed with this knowledge, physicians working in similar outpatient, subspecialty safety-net clinics can focus their vaccine education efforts appropriately. our study showed that 57.7% of dermatology patients from an urban safetynet hospital are willing to receive a covid19 vaccine and that safety concerns represent the main reason for patient hesitancy. this proportion of willing patients is similar to the cdc’s most recent data that demonstrated 52.4% of those eligible to be vaccinated have received a covid-19 vaccine.14 additionally, our findings are inline with recent surveys which indicate many people in the general population are concerned with vaccine safety.5 a systematic review of 30 articles analyzing willingness to receive a covid-19 vaccination during the first year of the pandemic found rates between 27.7%93.3% with significant differences when stratified by socio-demographic factors.15 for our dermatology cohort, only flu vaccination history, self-identified race/ethnicity, and having friends, relatives, or colleagues who tested positive for covid-19 correlated with patient attitude toward the vaccine. patients who did not regularly receive a flu vaccine, noncaucasian patients, and those with friends, family, or colleagues who tested positive for covid-19 were less willing to receive a covid-19 vaccine. a previous study similarly found that influenza vaccination was a positive predictor for acceptance of a covid-19 vaccine.16 additionally, previous survey studies have demonstrated that race/ethnicity often plays a role in vaccine acceptance.5,10 it was surprising that patients close to individuals who tested positive for covid-19 were more hesitant to receive a covid-19 vaccine, but this finding has been observed previously.16 while this avoidance predictor has not been thoroughly studied, it could be explained by a perceived low mortality rate of covid-19. these findings emphasize the need for vaccine discussion and education of these patient cohorts. patients who had a recent dermatology appointment were overall more willing to receive a covid-19 vaccine than those without a recent dermatology appointment. only 11% of the dermatology cohort was unwilling to receive a vaccine but 25.8% of the non-dermatology cohort was unwilling to receive a vaccine. the percentage of unwilling dermatology patients is lower than that of the general population given a recent survey study estimated over 20% of the general population does not intend to get a covid-19 vaccine.14 this finding may be explained by the increased health literacy and vaccine literacy of patients able to receive subspecialty care. navigating the healthcare system can be complex, and patients with low health literacy often encounter barriers to specialty care such as the need for a referral and active insurance.17 studies have also shown that patients with low health literacy are less likely to partake in preventative health behaviors such as immunization.18 interestingly, however, our study did not show a correlation between level of education and willingness to receive a skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 654 covid-19 vaccine, indicating that advanced education does not always correlate with vaccine acceptance. importantly, our study included a more ethnically diverse patient population than previous studies on vaccine acceptance.4,13 the majority of our surveyed patients identified as non-caucasian, and therefore our findings help to highlight the perspectives of a racially and ethnically heterogeneous population. additionally, our study focused on vaccine acceptance rates at an urban safety-net hospital and thus sheds light on the perspective of patients who might encounter more healthcare disparities than other patient populations. dermatologists should feel empowered in their ability to educate patients on the covid-19 vaccine. in our study, patients frequently expressed concerns that the covid-19 vaccine development appeared rushed and worried about the safety of vaccinations that had yet to receive fda approval. similarly, patients self-described as immunocompromised were weary of possible adverse side effects. other patients anecdotally cited histories of still getting the flu after receiving the influenza vaccine as reasons to doubt vaccine efficacy. when engaging with vaccine hesitant patients, dermatologists may turn to the evidencebased guidelines and scripts provided by the american academy of dermatology.19 therein, dermatologists can assure patients that the vaccines have been properly tested and are recommended for the vast majority of the population including immunocompromised individuals. likewise, dermatologists may combat the idea of “breakthrough” infections as being a failure of the vaccination process by providing patients with data demonstrating reduced disease severity and better covid-19 infection outcomes of those vaccinated vs. those unvaccinated.20 armed with such information, dermatologists will engage patients in shared decision-making that will hopefully translate into increased vaccine acceptance. there are several limitations to our study. first, our study only included patients from a single urban safety-net hospital, and therefore the findings are less generalizable to the overall united states population. additionally, our study was performed in the summer of 2020, and as new data about covid-19 and the vaccines emerge, patient attitude toward vaccination may change. despite these limitations, our results provide dermatologists, especially those working in urban safety-net clinics, with key information about the attitude of our patients toward the covid-19 vaccine. while significant challenges remain regarding the public’s willingness to receive the covid-19 vaccinations, dermatologists may feel empowered in their ability to aid patient decision-making and improve vaccine uptake. our study demonstrates that patients with a recent dermatology appointment are more willing to receive a covid-19 vaccine than those without a recent dermatology appointment, demonstrating the power of the tertiary care patient-provider relationship. non-caucasian patients were less willing to receive a covid-19 vaccination, most often due to safety concerns, highlighting the importance of outreach to these more traditionally marginalized patient populations. we hope that vaccine education for those populations most in-need will translate into increased vaccine acceptance now and as covid-19 boosters emerge and remain at the forefront of healthcare maintenance. conclusion skin november 2021 volume 5 issue 6 copyright 2021 the national society for cutaneous medicine 655 conflict of interest disclosures: none funding: none corresponding author: jacqueline watchmaker, md, southwest skin specialists 10900 n scottsdale rd #201 scottsdale, az 85254 phone: 480-591-3500 email: jacqueline.watchmaker@gmail.com references: 1. baden, l.r. et al. (2021) efficacy and safety of the mrna-1273 sars-cov-2 vaccine. n. engl. j. med. 384, 403–416 2. polack, f.p. et al. (2020) safety and efficacy of the bnt162b2 mrna covid-19 vaccine. n. engl. j. med. 383, 2603–2615 3. sadoff, j. et al. (2021) interim results of a phase 1-2a trial of ad26.cov2.s covid-19 vaccine. n. engl. j. med. 384, 1824–1835 4. reiter, p.l. et al. (2020) acceptability of a covid-19 vaccine among adults in the united states: how many people would get vaccinated? vaccine 38, 6500–6507 5. daly, m. and robinson, e. (2020) willingness to vaccinate against covid-19 in the us: longitudinal evidence from a nationally representative sample of adults from apriloctober 2020. medrxiv doi: 10.1101/2020.11.27.20239970 6. schaffer deroo, s. et al. (2020) planning for a covid-19 vaccination program. jama 323, 2458–2459 7. volpp, k.g. and cannuscio, c.c. (2021) incentives for immunity strategies for increasing covid-19 vaccine uptake. n. engl. j. med. 385, e1 8. pawelec, g. and picard, e. (2021) catch-ascatch-can: mrna vaccination boosts immune responses to sars-cov-2 variants. signal transduct. target. ther. 6, 259 9. wang, c. et al. (2021) sars-cov-2 (covid19) vaccination in dermatology patients on immunomodulatory and biologic agents: recommendations from the australasian medical dermatology group. australas. j. dermatol. 62, 151–156 10. lazarus, j.v. et al. (2021) a global survey of potential acceptance of a covid-19 vaccine. nat. med. 27, 225–228 11. attwell, k. and smith, d.t. (2018) hearts, minds, nudges and shoves: (how) can we mobilise communities for vaccination in a marketised society? vaccine 36, 6506–6508 12. thomson, a. et al. (2018) strategies to increase vaccine acceptance and uptake: from behavioral insights to context-specific, culturally-appropriate, evidence-based communications and interventions. vaccine 36, 6457–6458 13. xia, t. et al. (2019) understanding flu vaccination acceptance among u.s. adults: the health belief model and media sources. icrcc 2, 35–37 14. cdc covid data tracker. https://covid.cdc.gov/covid-datatracker/#vaccinations_vacc-total-admin-ratetotal. accessed september 6, 2021. 15. al-amer, r. et al. (2021) covid-19 vaccination intention in the first year of the pandemic: a systematic review. j. clin. nurs. doi: 10.1111/jocn.15951 16. dror, a.a. et al. (2020) vaccine hesitancy: the next challenge in the fight against covid-19. eur j epidemiol 35, 775–779 17. ezeonwu, m.c. (2018) specialty-care access for community health clinic patients: processes and barriers. j multidiscip healthc 11, 109–119 18. biasio, l.r. (2017) vaccine hesitancy and health literacy. hum. vaccin. immunother. 13, 701–702 19. covid-19 vaccine information. https://www.aad.org/member/practice/corona virus/vaccines. accessed august 30, 2021. 20. butt aa, nafady-hego h, chemaitelly h, et al. outcomes among patients with breakthrough sars-cov-2 infection after vaccination: breakthrough sars-cov-2 infection. int j infect dis. august 2021. doi:10.1016/j.ijid.2021.08.008 skin microbiome and acne vulgaris: staphylococcus, a new actor in acne b. dreno1,2, r. martin3, a. khammari1,2, d. moyal4, j.b. henley5, s. seite4 introduction methods results conclusion acne is a chronic inflammatory disease targeting the pilosebaceous follicle. propionibacterium acnes (p. acnes), the sebaceous gland and follicular keratinocytes play a role in the development of acne. together they induce inflammation in the follicle by activating the innate immunity. for several years, the role of staphylococcus, another bacterium genus, has been discussed in the development of acne. however, to date its role has never been demonstrated. the objective of this study was to investigate the characteristics of the microbiome on unaffected skin and acne lesions (comedone and papulo-pustular lesions) and to determine changes after applying either erythromycin 4% or a dermocosmetic containing lipohydroxy acid, salicylic acid, linoleic acid, niacinamide, piroctone-olamine, a ceramide and thermal spring water for 28 days. the study showed that in subjects with acne, the bacterial diversity is similar on the surface of unaffected skin as well as on comedones and papulopustular lesions. before and after treatment with either a topical antibiotic or a dermocosmetic, staphylococci remained the predominant genus of the superficial skin microbiota of acne lesions as well as of the unaffected skin. (1)department of dermato-cancerology, nantes university, nantes, france, (2)crcna, inserm u892, cnrs 6299, nantes, france, (3)l’oréal research & innovation, tours, france, (4)la roche-posay dermatological laboratories, asnières, france, (5)cooperative institute for research in environmental sciences, university of colorado, boulder, colorado, usa this single-centre controlled, randomized, double blinded, intra-individual study was conducted in 55 subjects with mild to moderate acne (gea grading)(1) before and after treatment either with a dermocosmetic formulation or a topical antibiotic. microbiota were collected with swabs at d0 and d28, under axenic conditions from 3 sites (comedones, papulo-pustular lesions and unaffected or clinically healthy looking skin) and characterised using a high-throughput sequencing approach that targets a portion of the 16s rrna bacterial gene(2). an overabundance of proteobacteria and firmicutes and an underrepresentation of actinobacteria on the skin surface of subjects with acne were observed. moreover, proteobacteria were less abundant in areas with comedones and papulo-pustular lesions than in unaffected skin areas (29% vs 34% p=0.001 and 31% vs 34% p=0.05) while firmicutes were more abundant in zones with comedones (52% vs 47% p=0.002). no difference for actinobacteria was evidenced. main bacterial phyla on the skin surface of the 3 sampled areas (comedones (b), papulo-pustules (c) and healthy skin (a)) at d0 (n=26) 13.7514.1413.6234.1 31.2928.9 p_proteobacteria • • • p=0.001 p=0.050 % 10 2 0 3 0 4 0 5 0 6 0 70 b c a b c a * * * • 52.01 * p=0.002 p=0.084 49.26 •% 3 0 2 0 4 0 5 0 6 0 70 8 0 p_firmicutes % 5 10 15 2 0 2 5 3 0 • • • * p=0.903 p=0.650 b c a p_actinobacteria 47.01• staphylococci were more abundant on the surface of comedones and papulo-pustular lesions (p=0.004 and p=0.003 respectively) compared to unaffected skin. propionibacteria represented less than 2% of the bacteria characterised. main bacterial phyla and genus in percentage at the skin surface of the 3 sampled areas (comedones, papulo-pustular and unaffected skin) at d0 (n=26) area phylum genus comedones (%) papulo-pustular (%) unaffected skin (%) actinobacteria propionibacterium corynebacterium other actinobacteria 13,61 1,04 7,93 4,64 14,15 1,20 8,54 4,40 13,75 1,36 7,71 4,69 firmicutes staphylococcus other firmicutes 52,01* 33,87* 18,14 49,27 34* 15,27 47,01 26,85 20,16 proteobacteria 28,90* 31,30* 34,10 bacteroidetes 4,16 3,78 3,73 fusobacteria 0,73 0,84 0,64 other 0,58 0,67 0,76 *p<0.05 versus unaffected skin staphylococcus genus at the skin surface of 3 sampled areas (comedones (b), papulo-pustules (c) and healthy skin (a)) in gea-2 (n=16) and gea-3 (n=10) at d0 after one month of treatment, erythromycin was mainly effective on actinobacteria while the dermocosmetic was effective on both actinobacteria and staphylococcus. main bacterial phyla and genus in percentage at the skin surface of the 3 sampled areas (comedones, papulo-pustular and unaffected skin) for the hemi-face receiving erythromycin 4% or the dermocosmetic after (day 28) treatment (n=26) day 28 erythromycin day 28 dermocosmetic phylum genus comedones (%) papulo-pustular (%) unaffected zone (%) comedones (%) papulo-pustular (%) unaffected zone (%) actinobacteria propionibacterium corynebacterium other actinobacteria 11,89* 0,82** 5,87* 5,20 11,09 0,82 5,72 4,56 11,98 1,22 5,88 4,89 11,56 0,64 7,37 3,56 10,87* 0,76 5,27* 4,84 11,25 1,06 4,95** 5,25 firmicutes staphylococcus other firmicutes 49,43 27,04 22,39 43,79 24,53** 19,30 45,80 24,91 20,91 44,55 19,96* 24,60 47,11 26,24** 20,89 46,40 23,52 22,92 proteobacteria 30,54 36,32 37,15 35,60 33,19 33,95 bacteroidetes 5,21 4,87 3,61 5,11 5,52 5,32 fusobacteria 0,62 0,49 0,38 0,65 0,81 0,51 other 2,27* 3,28* 1,01 2,48** 2,45 2,41** 1653.9 10 0 0 3 0 0 0 5 0 0 0 gea-2 gea-3 0.022 2636.2• a b 0 10 0 0 3 0 0 0 5 0 0 0 0 gea-2 gea-3 0.063 1719• 2662.4• 0 10 0 0 3 0 0 0 5 0 0 0 gea-2 gea-3 c 0.037 1262.6• 2167.5• • *p<0.05 versus day 0, **p<0.1 versus day 0 a b 20 15 10 5 0 d0 d28 p<0.0001 p<0.0001 comedones p=0.37 papulo-pustules p=0.88 0 5 10 15 d0 d28 9,4 5,2 20 15 10 5 0 d0 d28 p<0.0001 p<0.0001 0 5 10 15 d0 d28 15,3 11,9 16 11,8 9,7 5,2 in addition, a significant reduction of both comedones and papulo-pustular lesions with no significant difference between the products was observed. reduction of the number of papulo-pustular lesions and comedones on both hemi-faces after 28 days of treatment with either erythromycin (a) or the dermocosmetic (b) (n=26, values are expressed in mean±sd) references 1. dreno b, poli f, pawin h, et al. development and evaluation of a global acne severity scale (gea scale) suitable for france and europe. j eur acad dermatol venereol: 2011: 25: 43-48 2. caporaso jg, lauber cl, walters wa et al. global patterns of 16s rrna diversity at a depth of millions of sequences per sample. proc natl acad sci usa, 2011: 108 suppl 1: 4516-4522 in all 3 sampled areas, staphylococci proportions increased with the acne severity (p<0.05 between gea-2 and gea-3). fc17posterlarochedrenoskinmicrobiome.pdf skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 267 skimages lichen sclerosus et atrophicus nwanneoma ngonadi, msc1, claire hannah, md2, misha rosenbach, md2 1 university of virginia, school of medicine medical school, charlottesville, va 2 department of dermatology, hospital of the university of pennsylvania, philadelphia, pa a black woman in her 20s presented to dermatology with a three-year history of a slowly expanding eruption beneath her left breast. the rash was occasionally pruritic but otherwise asymptomatic. review of systems was notable for several months of vaginal irritation and pruritus, but no dysuria or dyspareunia. on physical exam, there were wrinkled, shiny, atrophic thin plaques with peripheral hyperpigmentation and central mottled hypo and hyperpigmentation involving the left breast, upper abdomen, and flank. on the left back there were clustered hyperpigmented papules. there was generalized edema and erythema of the vulva, without erosions, dyspigmentation, or sclerosis. rheumatologic workup, including antinuclear antibodies, rheumatoid factor, and anti-ro and anti-la antibodies, was negative. biopsies were performed from a hypopigmented plaque on the flank and a hyperpigmented papule on the back. both showed zones of faint homogenous hyalinization of the papillary dermis, dermal sclerosis with loss of cd34-positivity, lymphoplasmacytic periadnexal inflammation, and loss of fat consistent with a diagnosis of lichen sclerosus-morphea overlap. skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 268 the patient was initially treated with highpotency topical steroids, topical tacrolimus, and narrow-band ultraviolet b (uvb) phototherapy, but she had limited adherence and her rash continued to progress. she was started on hydroxychloroquine, and at 3-month follow up her pruritus had improved and the rash stabilized. her vulvar symptoms were found to be due candida and fully resolved on fluconazole. there were no features concerning for genital lichen sclerosus. lichen sclerosus et atrophicus (lsea), is a benign, chronic, lymphocyte-mediated inflammatory dermatosis affecting the dermis and the epidermis 1, 2, predominantly in anogenital areas. extragenital lsea is rare, with a prevalence of up to 0.3% 4. it affects all age groups, especially postmenopausal women and prepuberal girls (1). inadequately treated genital lsea can lead to atrophy, scarring, and physical dysfunction, with profound social, psychological, and sexual impacts 3. additionally, genital lsea increases the risk of vulvar squamous cell carcinoma by 4-5% 3, therefore, all patients with lsea should be asked about genital symptoms and a genital examination is recommended. extragenital disease typically presents with clusters of white or erythematous papules coalescing into plaques, which later become porcelain-white and atrophic with a wrinkled, cigarette paper-like appearance 2. as seen in our patient, hyperpigmentation can be a predominant feature in individuals with darker skin. the back, upper torso, armpits, forearms, and inframammary skin are commonly involved 1. the pathogenesis of lsea is thought to be due to the alteration of fibroblast function in the papillary dermis by inflammation, which results in fibrosis of the upper dermis 3. diagnosis of lsea is often made clinically or with biopsy, and while there is no cure, treatment can alleviate symptoms of discomfort such as itching, and reduce the risk of malignant transformation in genital lsea. therapeutic options for extragenital lsea include topical and intralesional corticosteroids, topical tacrolimus, and phototherapy3. lsea-morphea overlap should be managed similarly to morphea, with lower threshold to initiate immunosuppression. conflict of interest disclosures: none funding: none corresponding author: misha rosenbach, md department of dermatology hospital of the university of pennsylvania 3600 spruce st, 2 maloney philadelphia, pa 19104 email: misha.rosenbach@pennmedicine.upenn.edu references: 1. val, isabel phd; almeida, gutemberg phd an overview of lichen sclerosus, clinical obstetrics and gynecology: december 2005 volume 48 issue 4 p 808-817 doi: 10.1097/01.grf.0000179635.64663.3d 2. ganesan, l., parmar, h., das, j. k., & gangopadhyay, a. (2015). extragenital lichen sclerosus et atrophicus. indian journal of dermatology, 60(4), 420. https://doi.org/10.4103/0019-5154.160516 3. nair p. a. (2017). vulvar lichen sclerosus et atrophicus. journal of mid-life health, 8(2), 55–62. https://doi.org/10.4103/jmh.jmh_13_17 4. bergstrom, k. g, mengden, s. j, kamino, h., & ramsay, d. (2008). extragenital lichen sclerosus et atrophicus. dermatology online journal, 14(5). retrieved from https://escholarship.org/uc/item/3g0275rm skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 696 brief article a man with worsening scaling plaques and a new onset large draining ulcerated tumor hannah pile, do1, alexandra taylor, bs2, david altman, md1 1 st. joseph mercy hospital, ann arbor, mi 2 campbell university of osteopathic medicine, lillington, nc mycosis fungoides (mf) represents the most common form of cutaneous t-cell lymphoma, which is typically a progressive and chronic disease.1 there are multiple stages that classify the severity of the disease, which can range from generalized itching, to skin tumors, and finally a fully disseminated disease.2 mf may progress through a largecell transformation, a more aggressive form conferring a worse prognosis.1 the diagnosis of mf is usually made with a variety of techniques including histology, immunophenotyping and t-cell receptor gene analysis.3 treatment is multidisciplinary, requiring hematology and oncology referral and possibly investigational therapies.2 a 62-year-old male presented as a new patient for evaluation of a worsening eruption abstract mycosis fungoides (mf) is the most common form of cutaneous t-cell lymphoma, a rare condition which typically presents with erythematous patches and plaques, skin nodules and/or tumors. advanced disease may progress to a more aggressive form known as a largecell transformation (lct). mf may be easily confused for psoriasis, a deep fungal infection, and pyoderma gangrenosum. the name “mycosis fungoides” is misleading as the disease is not due to a fungal infection. psoriasis and mf share common features associated with the abnormal functioning of t cells, and in the absence of an infectious process, pyoderma gangrenosum (pg) may be considered. definitive diagnosis relies upon histopathology revealing characteristic features of mf including cerebriform nuclei, intraepidermal pautrier microabscesses, epidermotropism and haloed lymphocytes, ruling out the other etiologies. here is a case of a 62-year-old male with an atypical case of mf with lct who presented with worsening skin eruption and a large draining ulcerated abdominal plaque. mf is typically a slow and indolent disease with multiple treatment options. brentuximab vedotin (bv) is a monoclonal antibody targeting the cd30 antigen on cancer cells and is increasingly used in the treatment of mf patients with lct. the patient was referred to hematology/oncology where further workup revealed cd30 positive large t-cells. he was started on bv and has already shown signs of significant disease regression. introduction case report skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 697 on his arms, face, legs, and trunk. the rash was described as red, blistering, painful and had been present for the past eight months. the patient also reported a periumbilical plaque that started as a red-violaceous nodule which progressed to a large draining ulcerated plaque over the past six months. past medical history is significant for untreated psoriasis diagnosed 10-15 years prior. the patient has been washing his abdomen daily with soap and water and reported no cough, diarrhea, fevers, or joint aches. physical examination revealed scattered erythematous oval patches and plaques on his bilateral upper and lower extremities and trunk, with variable overlying scale. on the lower abdomen there was a 20 cm periumbilical ulcerated indurated tumor with adherent yellow-green fibrinous drainage (figure 1) the patient had significant cervical, axillary, and inguinal lymphadenopathy. punch biopsies from the periumbilical area and right ventral forearm were sent for histopathologic examination (figure 2 and 3). figure 1. ulcerated abdominal tumor. microscopic findings and clinical course histopathologic examination demonstrated irregular epidermal hyperplasia with patchy spongiosis. there are dense diffuse infiltrates of large atypical epithelioid to reniform cells with interspersed small lymphocytes and frequent eosinophils in the superficial and deep dermis (figure 3). the epidermis contained similar atypical cells, as well as eosinophils, as single units and small clusters. focal ulceration and necrosis were also found within the lesions. a cd3 stain marked most of the large dermal cells (figure 2). the patient was referred to hematology where further workup revealed cd30 positive large t-cells. the patient has been started on bv and has already shown signs of disease regression. figure 2. cd3 stain. mycosis fungoides (mf) is the most common subtype of cutaneous t-cell lymphoma and is characterized by the evolution of patches, plaques, tumors, and in some individual’s progression to a more aggressive form known as large-cell transformation (lct).1,2 discussion skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 698 while lct is very rare in early stage i of mf, it has been described in up to 50% of patients with stage iv disease.2 mf with lct typically confers a worse prognosis with 50% survival by 1 year compared to tumor stage mf without lct, which has an average survival of 5.5 years.2 figure 3. high power dermal infiltrate. classic mf presents with erythematous patches and/or plaques in the early stages, which may progress to thicker plaques, skin nodules and tumors.1 these mushroom-like tumors can ulcerate and are typically 1 to 15 cm in diameter presenting with a bluish or red-brown hue.3 while lct is most likely to occur in the tumor stage of disease, it has also been associated in smaller papules with rapid progression of disease which may help aid in early detection of transformation.3 the diagnosis of mf relies upon histology, immunophenotyping and t-cell receptor gene analysis.4 characteristic histologic features in mf include atypical mononuclear cells with cerebriform nuclei, intraepidermal pautrier microabscesses, epidermotropism and haloed lymphocytes.3 mf with lct is defined histopathologically as >25% of the population of cells being large (about 4 times the size of normal lymphocytes).3 the cells may display other atypical features such pleomorphism, lobulated nuclei, and cd30 positivity.2 psoriasis and mf share common clinical and pathogenetic features associated with the abnormal functioning of t cells.4 they are two distinct skin disorders that may coexist, present after one another or resemble each other, making differentiation increasingly difficult.5 additionally, repeated biopsies may not confirm mf for months to years. disease confirmation often requires a thorough exam, histopathology and t cell monoclonality.4 psoriasis is histologically characterized by epidermal hyperplasia, parakeratosis, neutrophils infiltrating the stratum corneum and spinous layer, hypogranulosis, and suprapapillary plate thinning with papillary blood vessel dilation.6 lymphadenopathy and internal organ involvement are much more likely to be seen in mf than psoriasis.6 tumor stage mf should be differentiated from other causes of indurated skin lesions. the name “mycosis fungoides” is misleading due to the fungal sounding nature of the name. however, mf is typically an indolent lymphoma with skin lesions that may resemble mushrooms.1 deep fungal infections may be diagnosed via pcr or culture.7 histologic evaluation of a skin biopsy would reveal a granulomatous process with fungal hyphae or yeast forms highlighted by periodic acid-schiff or grocott methenamine silver stains.7 in ulcerated skin lesions a gram-stain can be helpful at ruling out bacterial infections.7 in the absence of an infectious process, pyoderma gangrenosum (pg) may be considered. while the infiltrate of pg may be robust, it’s typically neutrophilic and lack the monoclonality and atypical t cells appreciated in mf.8 skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 699 mf is typically a slow and indolent disease with treatments including topical steroids, phototherapy, topical nitrogen mustard, methotrexate, interferons, oral retinoids, photopheresis and radiation.1 lct of mf typically displays a more aggressive disease course and confers a poor prognosis requiring a multidisciplinary treatment approach with referral to hematology/oncology.2 bv, an anti-cd30 monoclonal antibody, is an ideal treatment in cd30 positive mf patients with lct.9 overall bv is well tolerated when compared to other systemic and radiation therapies with the most common side effect being peripheral sensory neuropathy.9 while cutaneous manifestations are the hallmark of mf, a large draining ulcerated abdominal plaque is not a common presentation. this case runs through the appropriate diagnosis modalities and histopathological findings for mf with lct, in addition to ruling out other common etiologies. while prognosis is typically poor at later stages of disease, treatment with bv may slow disease progression in patients with these specific tumor markers. conflict of interest disclosures: none funding: none corresponding author: hannah pile, do 15596 nola circle livonia, mi 48154 phone: 425-770-4997 email: hannahdpile@gmail.com references: 1. abel ea, wood gs, hoppe rt. mycosis fungoides: clinical and histologic features, staging, evaluation, and approach to treatment. ca: a cancer journal for clinicians. 1993;43(2):93-115. 2. herrmann jl, hughey lc. recognizing large-cell transformation of mycosis fungoides. j am acad dermatol. 2012;67(4):665-672. 3. mycosis fungoides nord (national organization for rare disorders). accessed march 12, 2022. https://rarediseases.org/rarediseases/mycosis-fungoides/ 4. a diagnostic challenge: mycosis fungoides or psoriasis. j am acad dermatol. 2013;68(4):ab143. 5. diakomopoulos a, dalamaga m, papadavid e. understanding the enigmatic association between mycosis fungoides and psoriasis: report of two cases and review of the literature. metabolism open. 2021;12:100148. 6. vaudreuil am, stroud cm, hsu s. psoriasis mimicking mycosis fungoides clinically. dermatology online journal. 2017;23(5). doi:10.5070/d3235034934 7. gonzalez santiago tm, pritt b, gibson le, comfere ni. diagnosis of deep cutaneous fungal infections: correlation between skin tissue culture and histopathology. j am acad dermatol. 2014;71(2):293-301. 8. powell fc, su wpd, perry ho. pyoderma gangrenosum: classification and management. j am acad dermatol. 1996;34(3):395-409. doi:10.1016/s01909622(96)90428-4 9. goggins ca, gocke mt, jang s, desimone ja. oral mycosis fungoides with cd30 + large cell transformation successfully treated with brentuximab vedotin. jaad case rep. 2019;5(2):180-183. conclusion powerpoint presentation a prospective clinical utility study demonstrates that physicians use the 40-gene expression profile (40-gep) to guide clinical management decisions for medicare-eligible patients with cutaneous squamous cell carcinoma (cscc) matthew s. goldberg, md1,2; jennifer j. siegel, phd2; kelli ahmed, phd2; sarah j. kurley, phd2; aaron s. farberg, md3 1ichan school of medicine, ny 2castle biosciences, tx 3baylor scott & white health system, tx background › the 40-gep has demonstrated both analytical and improved clinical validity for risk stratification when compared to current staging systems, categorizing patients as low (class 1), moderate (class 2a), or high (class 2b) risk for regional or distant metastasis within 3 years of diagnosis. 1-3 › previously reported clinical utility studies of the 40-gep test have demonstrated its use in directing personalized risk-aligned patient management, inclusive of: follow-up, surveillance imaging, sentinel lymph node biopsy, and adjuvant radiation therapy 4-8 (table 1). this study was sponsored by castle biosciences, inc. (cbi), which provided funding to the contributing centers for tissue and clinical data retrieval. jjs, sjk, ka, and msg are employees and options holders of cbi. asf is a consultant for cbi. references results presented at fall clinical dermatology conference, october 20-23, 2022, las vegas nv for more information: skurley@castlebiosciences.com › in this ongoing, prospective clinical utility and health outcomes study (utilise), analysis 1 showed that for more than 80% of patients under study, clinicians reported that the 40-gep had a positive impact toward managing their high-risk scc patient (i.e., increased confidence in treatment plan, risk-aligned changes, and patient more on board). › the 40-gep impacts physicians’ assessment of risk for their patients with cscc, which, in line with guidelines, is driving risk-aligned changes in treatment plans. › the clinical actionability rates of the 40-gep for cscc are comparable to those of currently covered molecular tests for cancer patients, such as those gep tests for breast, prostate, and lung cancer. conclusions disclosures methods scan here for more info feature n (%) age (range) 65-90* male 38 (64.4) location on head or neck 43 (72.9) patient immunosuppressed 2 (3.4) neurologic symptoms at tumor site 1 (1.7) chronic inflammation at tumor site 2 (3.4) tumor diameter ≥2cm 21 (35.6) rapidly growing tumor 6 (10.2) poorly defined borders 10 (17.2) poor differentiation 1 (1.7) depth of invasion** beyond subcutaneous fat 1 (1.7) clark level iv or v 18 (30.5) breslow’s thickness ≥2mm 3 (5.1) lymphovascular invasion 1 (1.7) perineural invasion 2 (3.4) 40-gep result*** class 1 52 (88.1) class 2a 7 (11.9) *to maintain confidentiality, any age over 89 was reported as 90 **investigators were allowed to report depth of invasion using various options ***no class 2b risk scores were observed at the time of analysis table 2. patient demographics (n=59) of the medicare-eligible cohort figure 3. the 40-gep result is the most influential factor impacting clinicians’ management plans for 42% of patients *clinicopathologic factors as choice options: tumor size, location, depth, differentiation status, histological subtypes, perineural or lymphovascular invasion, immune status, patient age, history of cscc, medical history figure 1. design of utilise: a prospective, multi-center clinical utility study table 1. previously reported clinical utility studies support personalized risk-aligned changes in overall management plans after 40-gep testing from clinicians treating high-risk cscc patients study design cohort (n) findings teplitz, et al. 2019 prospectively designed study to determine impact of 40-gep on recommended patient management strategies 402 clinicians (3 patient vignettes) 40-gep test can significantly impact dermatologist management recommendations while remaining within the context of established guidelines. 4 farberg, et al. 2020 retrospectively designed study integrating 40-gep into nccn recommendations for patient management 300 patients patients were risk-aligned with low, moderate, or high intensity management plans based on 40-gep class results. 5 litchman, et al. 2020 prospectively designed study to determine impact of 40-gep on recommended patient management strategies 162 clinicians (2 patient vignettes) the 40-gep test results influenced changes in clinical management decisions for high-risk scc patients in a riskappropriate manner while remaining within established guidelines. 6 au, et al. 2021 case reports of patients retrospectively tested with 40-gep 2 patients the utility of the 40-gep test to provide additional information for guiding patient management decisions and improving outcomes is demonstrated by two cases with identical tumor staging, yet divergent outcomes. 7 hooper, et al. 2022 prospectively designed study to determine impact of 40-gep on recommended patient management strategies 34 real-world clinicians (6 real-world patients) the incorporation of the 40-gep class result had a significant impact on recommended patient management plans in a risk-appropriate manner while adhering to established guidelines. 8 1. wysong, et al jaad 2021 2. ibrahim, et al future oncol 2021 3. borman, et al diagn pathol 2022 4. teplitz, et al jdd 2019 5. farberg, et al cmro 2020 6. litchman, et al cmro 2020 7. au, et al dermatol ther 2022 8. hooper, et al cancer inv 2022 9. soliman, et al bmc cancer, 2020 10. martin, et al curr med res opin, 2015 11. asad, et al am j surg, 2008 12. gore, et al cancer, 2017 13. basourakos, et al, front. oncol, 2021 14. lee, et al, chest, 2021 clinical issue and objective management decisions for cscc patients are determined by the clinician’s evaluation of the risk of disease progression. contributing to the challenge for implementing risk-appropriate patient management are the limitations of staging systems and treatment guidelines in predicting poor outcomes. a prognostic 40 gene expression profile test (40-gep) has been validated to accurately stratify risk for metastasis in patients with one or more high risk factors.1-3 the objective of this ongoing prospective study is to capture the impact of 40-gep testing on clinician recommendations and actions for patients for clinical management of their cscc undergoing testing as part of their clinical care. *n=3 cases with missingness and risk factor count of zero. physician attested to eligibility for testing. p a ti e n ts ( % ) risk factor count* figure 2. clinicopathologic risk factor count for cohort › during an ongoing multi-center, prospective study (utilise: clinical utility and heath outcomes study of the prognostic 40-gep test) clinician recommendations for patient management were recorded before and after 40-gep testing, along with patient clinicopathologic factors, test results, and clinical management. › analysis 1 consists of 11 private practice clinicians, comprised of mohs surgeons (n=7), dermatologists (n=1), and physician assistants (n=3). › for the lead-in phase, physicians fill out a treatment plan assessment after ordering the 40-gep test but before receipt of results for 5 patients. details of patient management and outcomes are then collected at six-month intervals for three years. › then, clinicians enroll patients into the clinical utility phase which will include the addition of a second questionnaire to complete after receipt of 40-gep results. details of any changes in patient management will be tracked along with patient outcomes, including metastasis-free survival, for all patients every six months for three years. › this analysis 1 of the clinical utility phase of medicare-eligible patients enrolled in the study are reported here (n=59). 1 2 3 4 0 10 20 30 40 50 what is the patient’s risk of developing nodal or distant metastasis? pre-gep post-gep n % of class 1* pre-gep post-gep n % of class 2a 5-10% <5% 12 23.5% <5% 10-30% 3 42.9% 10-30% <5% 1 2.0% 5-10% 10-30% 2 28.6% what is the overall management recommendation for this patient? moderate low 8 15.7% low moderate 3 42.9% moderate high 1 14.3% class 1 40-gep aligned decrease in risk perception and treatment table 3. clinicians’ perception of metastasis likelihood and overall management intensity changes with 40-gep results no impact on treatment plan or confidence no change in treatment plan, but patient is more on board increased clinician confidence made changes based on 40-gep result 24% 24 % n=58* 59 % n=59 *n=1 case with no response 40-gep clinicopathologic factors* lead-in phase 40-gep results received clinical utility phase enrollment clinician fills out pre-test treatment plan clinician fills posttest treatment plan outcomes and data collection every 6 months for 3 years outcomes and data collection every 6 months for 3 years clinician successfully completes enrollment of ≥5 high-risk cscc patients enrollment clinician fills out pre-test treatment plan 40-gep results received *n=1 case with no response class 2a 40-gep aligned increase in risk perception and treatment figure 4. the 40-gep result positively impacted patient management in over 80% of patients 42% most influential factor 58% 15% 59%2% impact of 40-gep prognostic gep test (cancer) intended use overall change in management 40-gep (cscc) to guide treatment decisions in patients with cscc with one or more high-risk factors 24% 70-gep (breast) to guide therapy decisions in patients with early-stage breast cancer9 24% 50-gep (breast) to guide adjuvant treatment selection in patients with early-stage breast cancer10 20% 21-gep (breast) to guide adjuvant treatment selection in patients with early-stage breast cancer11 44% 22-gep (prostate) to guide decisions about adjuvant radiation therapy12 18% 17-gep (prostate) to guide treatment decisions, including active surveillance, prostatectomy, and radiation therapy13 18% 23-gep (lung) to guide invasive procedures, including surgery and surveillance in low/intermediate risk of lung malignancy14 25% table 4. overall management change in patients tested with the 40-gep compared to commonly used prognostic gep tests in other cancers https://castlebiosciences.com/research-development/publications/ skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 788 research letter epidemiology and mortality risk factors of sebaceous carcinoma: a seer – based population study joseph haquang1, rocky li1, kevin mai1, kuang cheng chen1, fardad sisan1, kuo yuling, md2 1 college of osteopathic medicine of the pacific, western university of health sciences pomona, ca 2 national taiwan university hospital– department of dermatology, taipei city, taiwan sebaceous carcinoma (sc) is a rare and potentially aggressive cutaneous malignancy most commonly derived from the sebaceous glands, the glands of zeis, or meibomian glands. the current literature search does not report which demographic and socioeconomic factors are associated with increased mortality risk.1 our article aims to build upon the limited prognostic research by abstract background: sebaceous carcinoma is a rare and potentially aggressive cutaneous malignancy. it is derived from the adnexal epithelium of sebaceous glands and tends to hold a diverse clinical presentation. although it is often reported in the periocular region, it can manifest from any sebaceous unit in the skin. due to the rarity of this condition, prognostic and demographic factors are largely indeterminate. hence, we sought to assess the prognostic impact of demographic and socioeconomic factors on the outcome of patients with sebaceous carcinoma. methods: a retrospective analysis was performed utilizing data from the surveillance, epidemiology, and end results (seer) database. from the registries, cases of sebaceous carcinoma from the years 2000 to 2018 were analyzed. univariate and multivariate cox regression analyses were used to analyze the significance of socioeconomic and demographic factors on the survival of sebaceous carcinoma. tumor grade and extent were included in the multivariate cox regression to minimize confounding. results: a total of 4154 cases of sebaceous carcinoma were analyzed within this study. socioeconomic and demographic factors analyzed includes age, sex, race, and income. on multivariate analysis including tumor grade, tumor extent, age, sex, race and income, african american race was a significant risk indicator for survival (hazard ratio [hr], 1.9; p=.007). increased age of 70+ were also identified as a significant risk indicator for survival (hr, 5.86; p<0.001). female sex was identified as a protective indicator for survival (hr, 0.82; p=0.03). income status did not significantly influence the survival outcome of sebaceous carcinoma. conclusion: although income status did not show any significant influence on the survival outcome of sebaceous carcinoma, sex, race, and age characteristics did. the etiology behind these prognostic factors is unclear but may be related to access to medical care or lack of social support. introduction skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 789 evaluating current data from 2000-2018 with a more extensive case number. our analysis reports the associated sc mortality risk of race, age, sex, and income. patients diagnosed with sc from 2000 to 2018 were identified in seer 18 registry using seer rare cancer classification variable “40.2 sebaceous adenocarcinoma”. the following data were extracted: age, year of diagnosis, race, vital status, site, combined summary stage, grade (degree of differentiation), extension, metastasis at diagnosis, tumor size, lymph nodes, and median household income inflation adjusted to 2019. survival was measured in months from time of diagnosis to loss of follow up which included all-cause mortality. multivariate cox regression model was conducted using covariates deemed clinically significant or with p value of less than 0.25 in univariate analysis to include all potential factors. age categories, sex, race, grade, tumor extent, and income were included in the final model.2-4 a total of 4154 patients with primary sc were identified. patient demographics and tumor characteristics are summarized in table 1. the majority of patients diagnosed were over 70 years of age, with a male predominance (61.7%). 85.8% of the patients were white. median and mean months of follow-up were 50 and 64. the results from the multivariate cox regression model are shown in table 2. older age at diagnosis is associated with lower survival, with highest mortality among those 70 and older (hr = 5.86 [95% confidence interval (ci) 3.62 9.51]). female sex is a protective prognostic predictor, with 18% reduction in mortality compared to their male counterparts (hr = 0.82 [95% ci 0.69 0.98]). black individuals with primary sc have lower survival than white individuals (hr = 1.9 [95% ci 1.19 3.03]). other variables such as income, location, and tumor extent do not have statistically significant association with survival in this model. we corroborate previous literature describing a higher incidence of sc in white individuals. our results demonstrated a statistically significant hr of 1.9 in individuals identifying as black, implying a higher mortality risk despite having a lower overall incidence of sc. various factors discussed by shao et al. regarding other skin cancers, such as acral lentiginous melanoma, could similarly explain the higher mortality in scc. for instance, reduced access to care leads to decreased early skin examination/detection rates, less awareness of melanoma, and misdiagnosis from varied clinical presentation.[5] geographical differences may also play a role leading to increased uv radiation exposure.[6] furthermore, age >70 had a significant hr of 5.86, and those 50-69 had a hr of 2.09. advanced age is a recognized risk factor for cutaneous malignancies and could be related to impaired immunologic and dna repair mechanisms that decline with age. interestingly, we could not conclude an association between socioeconomic status and mortality. possibly, the rarity of the condition requires a larger sample size to fully assess the association. finally, our study described a predominance in male sex. however, females had a hazard ratio of 0.82 which suggests a lower risk of mortality. this methods results discussion skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 790 table 1. patient demographics and tumor characteristics. characteristic number (percent) sex female 1592 (38.3%) male 2562 (61.7%) age 0-49 300 (7.2%) 50-69 1459 (35.1%) >70 2395 (57.7%) race white 3566 (85.8%) african american 115 (2.8%) asian/pacific islander 213 (5.1%) american indian/alaska native 29 (0.7%) unknown 231 (5.6%) tumor extent localized 2651 (63.8%) distant 141 (3.4%) regional 128 (3.1%) unknown 1234 (29.7%) site lip 38 (0.9%) eyelid 924 (22.2%) external ear 154 (3.7%) face 1414 (34.0%) scalp and neck 506 (12.2%) trunk 728 (17.5%) upper limb and shoulder 262 (6.3%) lower limb and hip 87 (2.1%) overlapping lesion 6 (0.1%) skin, nos 25 (0.6%) scrotum 10 (0.2%) grade i 515 (12.4%) ii 240 (5.8%) iii 340 (8.2%) iv 39 (0.9%) unknown 3020 (72.7%) metastasis metastasized 129 (3.1%) not metastasized 2978 (71.7%) skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 791 unknown 1047 (25.2%) income < $35,000 48 (1.2%) $35,000 39, 999 70 (1.7%) $40,000 44, 999 148 (3.6%) $45,000 49, 999 236 (5.7%) $50,000 54, 999 267 (6.4%) $55,000 59, 999 275 (6.6%) $60,000 64, 999 770 (18.5%) $65,000 69, 999 549 (13.2%) $70,000 74, 999 354 (8.5%) $75,000+ 1434 (34.5%) skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 792 table 2. cox regression multivariate analysis of overall survival of sebaceous carcinoma. characteristics hr (95% ci) age 0-49 1 50-69 2.09 (1.26-3.45) >70 5.86 (3.62-9.51) sex male 1 female 0.82 (0.69-0.98) race white 1 african american 1.9 (1.19-3.03) asian/ pacific islander 0.66 (0.43-1.02) american indian/ alaska native 1.21 (0.49-2.97) grade well differentiated 1 moderately differentiated 0.8 (0.63-1.02) poorly differentiated 1.21 (0.99-1.48) undifferentiated 1.26 (0.83-1.92) tumor extent localized 1 regional 1.21 (0.80-1.83) distant 1.35 (0.93-1.96) income < $35,000 1 $35,000 39, 999 2.15 (0.74-6.23) $40,000 44, 999 1.01 (0.37-2.77) $45,000 49, 999 0.88 (0.34-2.31) $50,000 54, 999 1.58 (0.62-4.0) $55,000 59, 999 1.12 (0.44-2.87) $60,000 64, 999 1.24 (0.50-3.05) $65,000 69, 999 1.16 (0.47-2.88) $70,000 74, 999 0.91 (0.36-2.32) $75,000+ 1.19 (0.49-2.91) hr: hazard ratio; ci: confident interval; * indicates statistically significant p value (<0.05) skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 793 finding could be explained by the influence of estrogen, behavioral differences, or other confounders.[7] of note, limitations in our interpretation arise from constraints in the seer database as recorded mortality includes deaths from any cause and losses to follow-up. thus, these factors could cause selection bias and skewing of our analysis. overall, increased data collection can lead to better clinical understanding and policy changes for sc patients. a systematic analysis incorporating several multi-regional studies could paint a more accurate picture of the influence of demographic and socioeconomic factors on sc. conflict of interest disclosures: none funding: none corresponding author: joseph haquang college of osteopathic medicine of the pacific, western university of health sciences pomona, ca email: joseph.haquang@westernu.edu references: 1. dasgupta, t., l.d. wilson, and j.b. yu, a retrospective review of 1349 cases of sebaceous carcinoma. cancer, 2009. 115(1): p. 158-65. 2. team, r.c., r: a language and environment for statistical computing. r foundation for statistical computing, vienna, austria. 2012. 2018. 3. team, r., rstudio: integrated development environment for r. rstudio, pbc, boston. 2020. 4. lin, h. and d. zelterman, modeling survival data: extending the cox model. 2002, taylor & francis. 5. shao, k. and h. feng, racial and ethnic healthcare disparities in skin cancer in the united states: a review of existing inequities, contributing factors, and potential solutions. j clin aesthet dermatol, 2022. 15(7): p. 16-22. 6. becker, g. and e. newsom, socioeconomic status and dissatisfaction with health care among chronically ill african americans. american journal of public health, 2003. 93(5): p. 742-748. 7. morgese, f., et al., gender differences and outcomes in melanoma patients. oncology and therapy, 2020. 8(1): p. 103-114. skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 487 research letter interim clinical utility findings of a transcriptomic psoriasis biologic test demonstrate altered physician prescribing behavior and improved patient outcomes bruce e. strober, md, phd1, michael bukhalo, md2, april w. armstrong, md3, david pariser, md4, leon kircik, md5, sepideh parhami, ms6, paul montgomery iii, ms6, and tobin j. dickerson, phd6 1 yale university school of medicine, new haven, ct 2 arlington dermatology, rolling meadows, il 3 department of dermatology, keck school of medicine, university of southern california, los angeles, ca 4 eastern virginia medical school & virginia clinical research, inc., norfolk, va 5 department of dermatology, icahn school of medicine at mount sinai, new york, ny 6 mindera health, san diego, ca abstract objective: this study (match) was designed to assess the clinical utility of a machinelearning based tool (mind.px) that predicts patient response to the most common biologic classes used in the management of psoriasis patients. methods: psoriasis patients who were biologic naïve or switching biologic were enrolled into the study (n=112). at baseline, a dermal biomarker patch was applied to lesional skin and mind.px test results provided to physicians prior to biologic selection. the choice of biologic for each patient was recorded and in the case of physician non-concordance with mind.px test results, a questionnaire completed to determine the reason for non-concordance. patients were evaluated at weeks 4, 8, 12, and 16 and statistical analysis between groups performed. results: physician prescribing behavior was measured with and without the inclusion of mind.px test results. this data was compared to previously obtained data in which dermal biomarker patches were applied at baseline, but mind.px results were not provided to physicians at any point during treatment (n=180). statistical analysis of concordance between the mind.px-informed and mind.px-uninformed groups within the match study (84.4% vs 53.8%, respectively) showed that when given access to mind.px results, physician behavior was significantly altered (p = 0.0022). furthermore, improved clinical outcomes in those patients whose physicians were provided mind.px test results was observed. specifically, this cohort reached pasi75 sooner than those who were not provided test results (p = 0.004). conclusion: these results provide an interim measurement of the clinical utility of mind.px by demonstrating that physicians will utilize this test in psoriasis biologic decision making and by doing so, this leads to improved patient outcomes. these improved patient outcomes can potentially translate into tremendous cost savings for healthcare systems. skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 488 in recent years, dermatology research has seen an influx of molecular data that when combined with bioinformatic methods, makes the promise of precision medicine a reality.1 indeed, the need for precision medicine in the treatment of moderate-to-severe psoriasis patients was highlighted in the most recent aad/npf guidelines.2 with the dramatic increase in spending on biologic drugs and an increasing array of biologic drugs available, physicians have been required to implement a trial-and-error paradigm to identify the best drug for a given patient. a precision medicine test (mind.px) has been reported that predicts patient response to biologic drug class with a positive predictive value >91%.3 this test uses a dermal biomarker patch that allows for rapid and painless extraction of mrna from skin, followed by transcriptomic analysis and machine learning-derived classifiers to provide actionable results for clinicians. here, we describe preliminary results from the match study4 that demonstrate a statistically significant difference in physician prescribing behavior when provided with mind.px test results, and measurable clinical benefit to those patients when concordant with mind.px results. in the match study, physician prescribing behavior was measured from a geographically diverse patient set with and without the inclusion of test results in the decision-making process (n=112; table 1). upon qualifying for the study, patients were randomized to either the informed or uninformed arms of the study. this data was compared to a previously reported data set in which dermal biomarker patches were applied at baseline,3 but test results were not provided to physicians at any point during treatment (stamp study, n=180). concordance between the test-informed and test-uninformed groups within the match study was markedly different (84.4% vs 53.8%, respectively), where concordance was defined as when physician choice matches mind.px test outcome. statistical comparison of these two groups showed that when given access to test results, physician behavior changed in a significant manner from those who used a standard of care treatment paradigm (p = 0.0022, fisher’s exact test); this trend was also observed when compared to the previously reported data set (84.4% vs. 62.8%, p = 0.0017). interestingly, the primary reason observed for physician non-concordance with test results came from payer formulary influence, suggesting that physicians were highly willing to use test results. a critical component of the demonstration of clinical utility is to not only show physician usage of a test result, but also that by using the test, those patients have better clinical outcomes relative to those without test results. in an interim analysis, we have examined those patients who have completed the match study and found that they showed improved clinical outcomes in those patients whose treatment was concordant with mind.px test results. in short, patients whose physicians were provided mind.px results reached pasi75 sooner than those who were not provided test results, and importantly, when compared against previously obtained observational data sets with identical inclusion/exclusion criteria,3 statistical significance was observed (p = 0.004; figure 1). these results validate our reported perceived clinical utility survey that showed 93% of physicians would follow the results of a precision medicine test for psoriasis biologic, independent of drug preference.5 future results from the match study may continue to strengthen the clinical utility of this transcriptomic test by demonstrating that skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 489 table 1. physician concordance with mind.px results. concordance is defined as when physician choice matches mind.px test outcome. importantly, in the mind.px-informed arm six out of seven patients were discordant due to insurance formulary restrictions. the remaining patient was discordant due to patient biologic preference mind.px informed tau concordant (%) 38 (84.4%) 21 (53.8%) discordant (%) 7 (15.6%) 18 (46.2%) figure 1. mosaic plot comparing patients who have completed the match study and those who completed the stamp study.4 here, red boxes are non-responders at 4 weeks and green boxes are responders at 4 weeks, with the number of patients in a group shown in each box. match-mnd is the informed arm where patient test results are provided, and match-tau is a treatment as usual arm where test results are not provided to physicians. this analysis shows that by using mind.px results, patients reach clinical endpoints faster than patients in treatment as usual arms. skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 490 physicians will utilize a precision medicine test in psoriasis biologic decision making and that by doing so, patient outcomes are improved relative to the standard of care. by prescribing patients the optimal biologic the first time, this test can lead to improved patient outcomes, while also potentially translating into tremendous cost savings for healthcare systems. precision medicine tools such as this have the potential to minimize the trial-and-error approach to the treatment of psoriasis, and provide physicians, patients, and payers with a powerful tool for improving the management of psoriasis patients. while this interim demonstrates statistically significant changes in physician behavior and improved patient outcomes from this behavior change, the cohort of patients who have currently completed the study is limited. future analysis as additional patients complete the study will be required. conflict of interest disclosures: bruce strober is a consultant (honoraria) for abbvie, almirall, amgen, arcutis, arena, aristea, asana, boehringer ingelheim, immunic therapeutics, bristol-myers-squibb, connect biopharma, dermavant, equillium, janssen, leo, eli lilly, maruho, meiji seika pharma, mindera health, novartis, pfizer, glaxosmithkline, ucb pharma, sun pharma, ortho dermatologics, regeneron, sanofi-genzyme, ventyxbio, and vtv therapeutics. he has received speaker honoraria from abbvie, eli lilly, janssen, and sanofi-genzyme. dr. strober is the co-scientific director of the corevitas (corrona) psoriasis registry, the editor-inchief (honoraria) of the journal of psoriasis and psoriatic arthritis, and has received research support from dermavant, abbvie, corrona psoriasis registry, dermira, cara, and novartis. michael bukhalo has served as a research investigator and/or advisor to boehringer ingelheim, novartis, leo pharma, eli lilly, dusa pharmaceuticals, merck, allergan, galderma, medimmune, centocor, and celgene. april armstrong has served as a research investigator and/or scientific advisor to abbvie, almirall, arcutis, aslan, beiersdorf, bi, bms, epi, incyte, leo pharma, ucb, janssen, lilly, mindera health, nimbus, novartis, ortho dermatologics, sun, dermavant, dermira, sanofi, regeneron, and pfizer. david pariser is a consultant (honoraria) for atacama therapeutics, bickel biotechnology, biofrontera ag, bristol-myers-squibb, celgene, dermira, leo pharma, mindera health, novartis, pfizer, regeneron, sanofi, theravida, and valeant. dr. pariser has also received research funding from almirall, amgen, aobiome, asana biosciences, bickel biotechnology, celgene, dermavant sciences, dermira, eli lilly, leo pharma, menlo therapeutics, merck, novartis, novo nordisk, ortho dermatologics, pfizer, and regeneron. leon kircik has served as a research investigator and/or scientific advisor to abbott laboratories, abbvie, allergan, almirall, amgen, arcutis, biogen-idex, bristol-myers-squibb, boehringer-ingleheim, breckinridge pharma, celgene, centocor, cellceutix, cipher, combinatrix, connetics, coria, dermavant, dermira, dow pharmaceutical sciences, dr. reddy’s lab, eli lilly, galderma, genentech, glaxosmithkline, idera, johnson & johnson, leo pharma, maruho, merck, medicis, novartis, promius, pharmaderm, pfizer, merck serono, stiefel laboratories, sun pharma, taro, ucb, valeant, and xenoport. sepideh parhami, paul montgomery iii, and tobin dickerson are employees of mindera health. funding: this study was funded by mindera health. corresponding author: bruce strober, md, phd phone: 860-322-2222 fax: 860-322-6838 email: brucestrober30@me.com references: 1. brownstone, n, wu jj, strober be, dickerson tj. getting personal about skin: realizing precision medicine in dermatology. dermatological reviews. 2021;2:289-295. 2. menter a, strober be, kaplan dh, et al. joint aad‐npf guidelines of care for the management and treatment of psoriasis with biologics. j am acad dermatol. 2019;80:1029‐1072. 3. bagel j, wang y, montgomery p iii, et al. a machine learning-based test for predicting response to psoriasis biologics. skin the journal of cutaneous medicine. 2021;5:621– 638. 4. strober b, fox j, jekowsky e, et al. evidence threshold for a precision medicine test that predicts optimal response to a biologic agent in patients with psoriasis: a consensus panel. j drugs dermatol. 2022;21:630-636. skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 491 5. strober b, pariser d, deren-lewis a, et al. a survey of community dermatologists reveals the unnecessary impact of trial-and-error behavior on the psoriasis biologic treatment paradigm. dermatol ther (heidelb). 2021;11:1851-1860. skin may 2022 volume 6 issue 3 263 (c) 2022 the authors. published by the national society for cutaneous medicine. compelling comment space medicine the next frontier for dermatology vignesh ramachandran, md1 1the ronald o. perelman department of dermatology, nyu langone health, new york, ny since human space exploration began with the vostok 1 in 1961, astronauts, cosmonauts, and taikonauts have been subjected to the effects of microgravity. microgravity alters the normal physiology of cells and tissues observed on earth and there are also spaceflight-related exposures that contribute to disease states. the study of these effects at the organ system level reveals several adverse effects in space voyagers, including cardiovascular dysfunction, vision impairment, genitourinary complications, and immune system impairments.1-3an understudied organ system, however, is the skin and the document and theoretical pathologies that might arise during spaceflight. this has ramifications for the dermatology community that have been briefly introduced in the past,4 but have not gone into illustrating the dearth of dermatologists involved in space medicine. this article highlights some of the dermatologic complications have arisen in spaceflight and theoretical pathologies while announcing a call to action for the dermatology community to become involved in research and clinical efforts within this niche, yet rapidly growing field. dermatologic complaints that have been documented by the national aeronautics and space administration (nasa) thus far have been relatively benign such as an episode of mild contact dermatitis after exposure to a biosensor electrolyte paste experienced by the commander of apollo 12.4 other astronauts have experienced symptoms such as dry, itchy skin, heightened sensitivity, and an increased risk for skin infections.2 furthermore, kailas and hoenig have discussed the abrasive and cytotoxic effects of lunar dust on skin cells.5 while these conditions contribute to morbidity, they have not resulted in outright mission failure. however, consideration of more sinister theoretical ailments secondary to decreased immune system function in space should be given and the role dermatologists might play in this sphere. astronauts undergoing long-duration spaceflight have experienced increased latent viral reactivation measured by increased shedding of epstein-barr virus, varicella-zoster virus, and cytomegalovirus.6 while the cutaneous manifestations of epstein-barr virus and cytomegalovirus are either benign or present in the immunocompromised and newborns, documented reactivation of varicella-zoster virus in astronauts poses concern for the possibility of zoster outbreak in spaceflight. while the astronauts who demonstrated increased viral shedding of varicella-zoster virus were asymptomatic, the combination of a suppressed immune system and the isolated, unfamiliar, and stressful space environment (further suppressing astronauts’ immune systems through increased cortisol skin may 2022 volume 6 issue 3 264 (c) 2022 the authors. published by the national society for cutaneous medicine. production), may predispose to a symptomatic zoster episode. similarly, a decrease in cell-mediated immunity has implications for common dermatologic disorders such as psoriasis. psoriasis is an autoimmune condition that implicates components of cellular immunity such as the major histocompatibility complex and t lymphocytes. far from a theoretical dermatologic condition of spaceflight, psoriasis has been a documented medical complaint of astronauts during the space shuttle missions (1988-1995).7 at present, dermatologic conditions, including psoriasis, are not disqualifying factors in astronaut selection. nevertheless, careful consideration and management of this condition and similar autoimmune diseases of the skin is warranted. abrasive/traumatic skin contact with spacesuits during training and during extravehicular activities may lead to worsening of symptoms via köebnerization. furthermore, as previously described, the combination of factors during spaceflight may predispose to psoriatic flares and, possibly, joint involvement during longduration voyage far from standard medical facilities. on another note, the effects of radiation exposure during spaceflight have implications for skin malignancies, further highlighting the role of dermatologists in space medicine. the nasa longitudinal study of astronaut health report in 2004 studied the men and women who have been selected as nasa since the formation of the space program in 1959. this study documented 33 cases of basal cell and squamous cell carcinomas, representing a three-fold increased risk compared to a control cohort. furthermore, two diagnoses of malignant melanoma were reported, both of which resulted in fatalities.8 while the study discusses the outdoor exposure astronauts experience during training and recreation as a contributing or confounding factor, we are nevertheless unable to discount the overall risks of being an astronaut from consideration. despite spacecraft and suit designs that attempt to limit radiation, astronauts still experience considerable occupational radiation; it has been suggested that astronauts experience approximately 502,000 millisieverts (msv) of ionizing radiation exposure during a six-month international space station mission.9,10 a study by azizova et al notes that the risk of nonmelanoma skin cancers is significantly increased in workers occupationally exposed to ionizing radiation at cumulative doses above 2.0 sv (rr = 2.52; 95% ci: 1.60, 3.97) compared to reference group (0–0.05 sv).11 superficial infection is an additional important consideration in spaceflight and an area of expertise in dermatology. the international space station has been noted to be colonized with numerous bacteria, including staphylococcus, micrococcus, bacillus, streptococcus, and even some fungal species.12 similarly, the russian mir has been documented to be colonized with species such as escherichia coli, serratia marcescens, legionella, spirochetes, and more.13 the confined quarters and inability to thoroughly clean the spacecraft during missions contribute to infection risk. in fact, commonly reported is the colonization and transfer of staphylococcus aureus species between astronauts.14 during missions, it would be important to identify preventative decolonization measures and acute management of superficial infections. furthermore, novel pathogenic species encountered during missions to other planets in the future may benefit from the shared expertise of dermatologists and infectious diseases specialists. flares of known dermatologic conditions have been documented to impact astronauts during training and even resulted in changes skin may 2022 volume 6 issue 3 265 (c) 2022 the authors. published by the national society for cutaneous medicine. in assigned mission roles. for instance, worsening of atopic dermatitis has been documented due in part to the dry conditions aboard the international space station.15 additionally, a diagnosis of idiopathic urticaria, identified prior to training or during training, would categorize an astronaut candidate as potentially unfit to fly while a history of angioedema and anaphylaxis are definite contraindications. during spaceflight, urticaria may result from decompression sickness which may occur during extravehicular activities.16 appropriate management, without impacting cognition, is mission-critical and would benefit from dermatologists’ input. although the previously highlighted dermatologic conditions are not an all-inclusive list, they do highlight the important role the dermatology community can play in space medicinea role that is markedly lacking. in fact, the author of this present paper has conducted an analysis of the aerospace medicine faculty of the consortium of 12 institutions that comprise the national space biomedical research institute, nasa flight surgeon biographies, and aerospace medicine residency trainee profiles. various specialties ranging from internal medicine, emergency medicine, neurology, urology, cardiology, orthopedic surgery, and more are represented. notably missing from the list are dermatologists. as humankind voyages to planets beyond and as commercial space travel have captured our fascination in recent times, the risk of dermatologic conditions manifesting in spaceflight conceivably increases. herein serves as a call for action to the dermatology community to actively engage in the discipline of space medicine, which would greatly benefit from our specialty’s expertise. the complexity of cutaneous disease in space overflows into concepts such as altered pharmacodynamic/pharmacokinetics of drugs in space, the absence of gravity influencing vehicles for topical medication delivery, cost considerations of identifying the most versatile medications/treatment modalities to transport to the space station, screening astronaut and civilian populations prior to inclusion for spaceflight, and participating in astronaut healthcare through performing skin checks and managing dermatologic diseases during training and via telemedicine with astronauts in space. these areas and more would benefit from dermatologists’ contributions. truly, by participating in space medicine, the dermatology community will be embarking on a new frontier one that is both mystifying and far from home, but not devoid of dermatological ailments. conflict of interest disclosures: none funding: none corresponding author: vignesh ramachandran, md the ronald o. perelman department of dermatology new york university email: vignesh.ramachandran@nyulangone.org references: 1. williams d, kuipers a, mukai c, thirsk r. acclimation during space flight: effects on human physiology. cmaj. 2009;180(13):13171323. doi:10.1503/cmaj.090628 2. tronnier h, wiebusch m, heinrich u. change in skin physiological parameters in space--report on and results of the first study on man. skin pharmacol physiol. 2008;21(5):283-92. doi: 10.1159/000148045. epub 2008 jul 28. pmid: 18663342. 3. crucian b, stowe rp, mehta s, quiriarte h, pierson d, sams c. alterations in adaptive immunity persist during long-duration spaceflight. npj microgravity. 2015 sep 3;1:15013. doi: 10.1038/npjmgrav.2015.13. pmid: 28725716; pmcid: pmc5515498. 4. burgdorf whc, hoenig lj. dermatology and the american experience in space. jama dermatol.2015;151(8):877. doi:10.1001/jamadermatol.2014.2557 5. kailas a, hoenig lj. moon dust. jama dermatol. 2017;153(10):1014. doi:10.1001/jamadermatol.2017.3341 mailto:vignesh.ramachandran@nyulangone.org https://doi.org/10.1038/s41526-017-0015-y https://doi.org/10.1038/s41526-017-0015-y https://doi.org/10.1038/s41526-017-0015-y https://doi.org/10.1038/s41526-017-0015-y https://doi.org/10.1038/s41526-017-0015-y https://doi.org/10.1038/s41526-017-0015-y https://doi.org/10.1038/s41526-017-0015-y https://doi.org/10.1038/s41526-017-0015-y https://doi.org/10.1038/s41526-017-0015-y https://doi.org/10.1038/s41526-017-0015-y https://doi.org/10.1038/s41526-017-0015-y https://doi.org/10.1038/s41526-017-0015-y https://doi.org/10.1038/s41526-017-0015-y https://doi.org/10.1038/s41526-017-0015-y https://doi.org/10.1038/s41526-017-0015-y https://doi.org/10.1038/s41526-017-0015-y https://doi.org/10.1038/s41526-017-0015-y https://doi.org/10.1038/s41526-017-0015-y https://doi.org/10.1038/s41526-017-0015-y https://doi.org/10.1038/s41526-017-0015-y https://doi.org/10.1038/s41526-017-0015-y https://doi.org/10.1038/s41526-017-0015-y https://doi.org/10.1038/s41526-017-0015-y skin may 2022 volume 6 issue 3 266 (c) 2022 the authors. published by the national society for cutaneous medicine. 6. mehta, s.k., laudenslager, m.l., stowe, r.p. et al. latent virus reactivation in astronauts on the international space station. npj microgravity 3, 11 (2017). https://doi.org/10.1038/s41526-0170015-y 7. wotring, virginia e. monitoring astronaut health in space.ntrs nasa technical reports server. https://ntrs.nasa.gov/archive/nasa/casi.ntrs.nasa .gov/20140004426.pdf. may 5, 2014. 8. institute of medicine (us) committee on the longitudinal study of astronaut health; longnecker de, manning fj, worth mh jr., editors. review of nasa's longitudinal study of astronaut health. washington (dc): national academies press (us); 2004. available from: https://www.ncbi.nlm.nih.gov/books/nbk215989 /doi: 10.17226/10903 9. cucinotta fa, durante m. cancer risk from exposure to galactic cosmic rays: implications for space exploration by human beings. lancet oncol. 2006 may;7(5):431-5. doi: 10.1016/s1470-2045(06)70695-7. 10. cucinotta fa, kim mh, willingham v, george ka. physical and biological organ dosimetry analysis for international space station astronauts. radiat res. 2008 jul;170(1):127-38. doi: 10.1667/rr1330.1. 11. azizova tv, bannikova mv, grigoryeva es, rybkina vl. risk of malignant skin neoplasms in a cohort of workers occupationally exposed to ionizing radiation at low dose rates. plos one. 2018;13(10):e0205060. 2018 oct 5. doi:10.1371/journal.pone.0205060 12. stabler ra, rosado h, doyle r, et al. impact of the mk viskinsuit on skin microbiota of terrestrial volunteers and an international space station-bound astronaut. npj microgravity. 2017;3(1):23. 13. ott cm, bruce rj, pierson dl. microbial characterization of free floating condensate aboard the mir space station. microb ecol 2004;47:133-6. 14. taylor gr. recovery of medically important microorganisms from apollo astronauts. aerospace med.1974; 45:824-828. 15. grover s. skin in aviation and space environment. indian j dermatol venereol leprol. 2011;77:413-7 16. arora s. aerospace dermatology. indian j dermatol. 2017;62(1):79 https://doi.org/10.1038/s41526-017-0015-y https://doi.org/10.1038/s41526-017-0015-y https://doi.org/10.1038/s41526-017-0015-y https://doi.org/10.1038/s41526-017-0015-y https://doi.org/10.1038/s41526-017-0015-y https://ntrs.nasa.gov/archive/nasa/casi.ntrs.nasa.gov/20140004426.pdf https://ntrs.nasa.gov/archive/nasa/casi.ntrs.nasa.gov/20140004426.pdf skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 539 brief article an atypical case of granulomatosis with polyangiitis with cutaneous features in a 19-year-old female daniel l. fischer, do, ma1, rebeca teplitz, do1, graham litchman, do, ms1, suzanne s. rozenberg, do, faocd, faad1 1 st. john’s episcopal hospital, far rockaway, ny granulomatosis with polyangiitis (gpa), formerly known as wegener’s granulomatosis, is a rare anca-associated, necrotizing vasculitis of the medium and small vessels. the annual incidence is 10-20 cases per million globally and 3 per million in the u.s. with an average age of onset of 6475 years. it is most common among northern european caucasians.1 although the pulmonary and renal systems are most commonly impacted, gpa manifests with cutaneous findings in approximately 34% of patients. skin lesions may be the initial presenting finding in about 13% of patients, however they do not typically manifest until 12-15 months of disease onset.2 the most common skin finding is palpable purpura involving the lower extremities (16%), followed by painful subcutaneous nodules(9.4%), maculopapular rash (6.7%), and papulonecrotic lesions that typically affect the face, scalp, and extremities(4.76%).3,4 here we discuss a case of a 19-year-old hispanic female who presented to our consult service with painful sanguineous skin lesions on the head, neck, arms, axilla, and back that had begun 3 weeks prior to admission. associated symptoms included fevers, palpitations, excessive sweating, arthralgias, productive cough with hemoptysis, nasal discharge, ocular pain, and a 20-lb weight loss over 6 months. the patient had been recently diagnosed with hyperthyroidism and managed on propranolol prior to admission. on examination, the patient presented with 13mm punched-out-appearing, tender and hemorrhagic ulcerations and subcutaneous nodules on the cheeks, jaw, neck, upper arms, axilla, and back (figure 1). a 4mm punch biopsy of a lesion on the upper back was sent for h&e, and lab work, imaging studies, and serologies were ordered. introduction case report skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 540 figure 1. punched out ulcerations on face (top left and right), axilla (bottom left), and arm (bottom right). histopathology demonstrated granulomatous dermatitis with extravasated erythrocytes, fibrin, and suppurative inflammation. canca/anti-pr3 were positive and p-anca, myeloperoxidase, and anti-gbm were negative (figure 2). h&e of a biopsy performed on the intranasal wall demonstrated granulation tissue with an admixture of neutrophils, plasma cells, lymphocytes, eosinophils, and multinucleated giant cells (figure 2). chest ct demonstrated pulmonary cavitations and sinus ct showed signs of multiple resections, however the patient had not had any prior sinus procedures. in addition, the patient had a low tsh and free t4, high tsh receptor antibody, and a hypervascular thyroid on ultrasound. figure 2. h&e shows granulomatous dermatitis with extravasated erythrocytes, associated fibrin, and suppurative inflammation. although gpa is a rare condition, cutaneous lesions present in only a minority of cases and typically on the lower extremities. this case demonstrated further atypicality as cutaneous findings were present above the trunk only and materialized fairly early in the disease process. in addition, the patient was 19 years old, significantly below peak incidence, non-caucasian, and had an accompanying thyroiditis. hyperthyroidism is an extremely rare concomitant finding in patients with gpa, described only in few case reports, with an estimated prevalence of about 1%. in addition, thyroid disease is more common in p-anca vasculitides rather than c-anca.5 in this case, the patient presented with concomitant thyrotoxicosis. although uncommon, cutaneous lesions can be among the initial prominent findings in patients with atypical presentations of gpa, and thus may serve as a crucial tool in discussion conclusion https://paperpile.com/c/nuoy1h/kyn1 skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 541 diagnosing this systemic and often fatal disease. conflict of interest disclosures: none funding: none corresponding author: daniel fischer, do, ma st. john’s episcopal hospital phone: (818) 800-6029 email: drdeefish@gmail.com references: 1. e. ntatsaki, r. a. watts, and d. g. i. scott, “epidemiology of anca-associated vasculitis,” rheum. dis. clin. north am., vol. 36, no. 3, pp. 447–461, aug. 2010. 2. l. e. gibson, u. specks, and h. homburger, “clinical utility of anca tests for the dermatologist,” int. j. dermatol., vol. 42, no. 11, nov. 2003, doi: 10.1046/j.13654362.2003.01914.x. 3. g. ragab, m. t. hegazy, m. ali, m. r. e. abdel-halim, and x. puéchal, “three patterns of cutaneous involvement in granulomatosis with polyangiitis,” journal of advanced research, vol. 24, p. 311, jul. 2020. 4. r. micheletti, z. chiesa, a. craven, r. watts, r. luqmani, and p. merkel, “lb943 cutaneous manifestations of ancaassociated vasculitis are common, varied, and associated with systemic disease,” journal of investigative dermatology, vol. 137, no. 10. p. b3, 2017. doi: 10.1016/j.jid.2017.07.016. 5. s. lionaki et al., “association between thyroid disease and its treatment with anca small-vessel vasculitis: a case–control study,” nephrol. dial. transplant, vol. 22, no. 12, pp. 3508–3515, aug. 2007. http://paperpile.com/b/nuoy1h/vp0e http://paperpile.com/b/nuoy1h/vp0e http://paperpile.com/b/nuoy1h/vp0e http://paperpile.com/b/nuoy1h/vp0e http://paperpile.com/b/nuoy1h/vp0e http://paperpile.com/b/nuoy1h/vp0e http://paperpile.com/b/nuoy1h/jynf http://paperpile.com/b/nuoy1h/jynf http://paperpile.com/b/nuoy1h/jynf http://paperpile.com/b/nuoy1h/jynf http://paperpile.com/b/nuoy1h/jynf http://paperpile.com/b/nuoy1h/jynf http://dx.doi.org/10.1046/j.1365-4362.2003.01914.x. http://dx.doi.org/10.1046/j.1365-4362.2003.01914.x. http://paperpile.com/b/nuoy1h/0adm http://paperpile.com/b/nuoy1h/0adm http://paperpile.com/b/nuoy1h/0adm http://paperpile.com/b/nuoy1h/0adm http://paperpile.com/b/nuoy1h/0adm http://paperpile.com/b/nuoy1h/0adm http://paperpile.com/b/nuoy1h/0adm http://paperpile.com/b/nuoy1h/0adm http://paperpile.com/b/nuoy1h/i3fh http://paperpile.com/b/nuoy1h/i3fh http://paperpile.com/b/nuoy1h/i3fh http://paperpile.com/b/nuoy1h/i3fh http://paperpile.com/b/nuoy1h/i3fh http://paperpile.com/b/nuoy1h/i3fh http://paperpile.com/b/nuoy1h/i3fh http://paperpile.com/b/nuoy1h/i3fh http://paperpile.com/b/nuoy1h/i3fh http://dx.doi.org/10.1016/j.jid.2017.07.016. http://paperpile.com/b/nuoy1h/kyn1 http://paperpile.com/b/nuoy1h/kyn1 http://paperpile.com/b/nuoy1h/kyn1 http://paperpile.com/b/nuoy1h/kyn1 http://paperpile.com/b/nuoy1h/kyn1 http://paperpile.com/b/nuoy1h/kyn1 http://paperpile.com/b/nuoy1h/kyn1 http://paperpile.com/b/nuoy1h/kyn1 http://paperpile.com/b/nuoy1h/kyn1 powerpoint presentation patients with t1–t2 tumors from previously published multicenter cohort studies who had undergone the slnb procedure were analyzed by both the i31-gep and the mskcc nomogram (n=465).6 accuracy metrics were compared using <5% predicted risk as a negative result and ≥5% as a positive result. the i31-gep for sentinel lymph node (sln) biopsy outperforms the mskcc nomogram in predicting the risk of having a positive sln in patients with cutaneous melanoma background › national comprehensive cancer network (nccn) guidelines recommend foregoing sentinel lymph node biopsy (slnb) if the population-based pointestimate risk of positivity is <5% (t1a with no high-risk features), discuss and consider slnb if the risk is 5-10% (t1a with high-risk feature(s), t1b), and recommend slnb if the risk is >10% (t2-t4).1 › with the current slnb positivity rate at approximately 12%,2,3 better tools are needed to refine patient selection for the procedure to avoid potential complications and additional healthcare costs. such methods that improve patient selection of those who will have a positive slnb, while identifying the correct patients with low enough risk (<5% positivity risk by current guidelines) that they can safely forego slnb could reduce the number of unnecessary surgical procedures, lower healthcare costs, and improve patient care. › two tools, the i31-gene expression profile test for slnb (i31-gep for slnb)4 and the nomogram developed at the memorial sloan kettering cancer center (mskcc)5,6 predict the risk of sln positivity in patients with cutaneous melanoma (cm) by combining a tumor’s molecular risk profile, clinical and pathological factors (i31-gep test) clinical and pathological factors only (mskcc). › we compared the performance of the i31-gep for slnb result prediction to that of the mskcc nomogram. acknowledgments & disclosures references › funding provided by castle biosciences. › dz and nb have no conflicts of interest. skm is an employee and stock/options holder at castle biosciences. methods presented at the 2023 winter clinical-miami dermatology conference. danny zakria, md1, sonia k. morgan-linnell, phd2, nicholas brownstone, md3 1department of dermatology, icahn school of medicine at mount sinai, new york, ny; 2castle biosciences, inc., friendswood, tx; 3department of dermatology, temple health, philadelphia, pa › the mskcc nomogram using clinical and pathological factors alone had a 10% miss rate in patients it predicted to have <5% risk of sln positivity—worse than ajcc staging alone. › the i31-gep for slnb missed 2.7%, significantly lower than mskcc—better than both mskcc and ajcc staging. › the i31-gep for slnb showed an 89% increase in the number of patients who could forego slnb compared with current guidelines (36:1 vs. 19:1 true to false negative ratio) compared with a 53% decrease if using mskcc. › the i31-gep for slnb has demonstrated clinical utility to guide slnb decisions in patients with t1-t2 tumors as well as guiding subsequent treatment plans with risk-of-recurrence. conclusions scan or click here for more info 1. national comprehensive cancer guidelines, v2, 2022. 2. joyce km, et al. ir j med sci 186:847–853, 2017. 3. chen et al. oncotarget 7:45671-45677. 4. whitman ed, et al. jco precision oncology 1466–1479, 2021. 5. wong sl, et al. ann surg oncol 12:282–288, 2005. 6. pasquali s, et al. eur j surg oncol 37:675–80, 2011. figure 1. i31-gep slnb guidance results in fewer missed positive slns than the mskcc nomogram or standard staging guidance › the i31-gep had a significantly lower false negative rate (3/111; 2.7%) than the mskcc nomogram (11/110; 10.0%) (p=0.026). › the i31-gep also had a lower false negative rate than using ajcc staging, which does not recommend slnb if the risk is 5% or less. table 1: variables included in i31-gep test or mskcc model prediction variables included in i31-gep test included in mskcc model 31-gep continuous score √ breslow thickness √ √ mitotic rate √ ulceration √ √ age √ √ clark level √ tumor location √ table 3. reclassification of risk in patients with 5-10% risk (nccn/ajcc t1b tumors) for whom guidance is not definitive test predicted <5% risk positivity rate in <5% group predicted >10% risk positivity rate in >10% group total reclassified i31-gep 36.2% (46/127) 2.2% (1/46) 15.7% (20/127) 15% (3/20) 52.0% (66/127) mskcc 29.9% (38/127) 7.9% (3/38) 2.4% (3/127) 0% (0/3) 32.3% (41/127) all results are % (n/n). i31-gep mskccajcc table 2. the i31-gep for slnb has higher accuracy than mskcc for predicting sln positivity in patients with t1-t2 tumors test sensitivity specificity negative predictive value positive predictive value i31-gep 94.8% 26.5% 97.3% 15.5% mskcc 81.0% 24.3% 90.0% 13.2% 19:1 9:136:1 missed positive slntrue negative sln (safely forego slnb) 31-gep: better than standard of care mskcc: worse than standard of care 1 missed positive sln per 37 considered low-risk 1 missed positive sln per 20 considered low-risk 1 missed positive sln per 10 considered low-risk › using only clinical and pathologic features to predict sln status limits the ability to identify tumors with spread to the sln (e.g., 12% positivity rate). integrating clinical and pathological factors with molecular tumor biology assessed by the prospectively validated gene expression risk profile (31-gep) improves risk stratification to guide personalized patient care. › beyond the utility for slnb guidance, the integrated 31-gep ( i31gep) also provides a precise risk for recurrence, metastasis, and disease-specific mortality for an individual patient. clinical impact 31-gep score, breslow thickness, mitotic rate, age, and clark level were continuous variables. ulceration was present or absent, and tumor location was entered as trunk, extremity, or head/neck. tumor location was evaluated in development of the i31-gep but was not significant for prediction; clark level was not evaluated because most providers use breslow thickness instead. https://castlebiosciences.com/research-development/publications/ slide 1 skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 149 brief article ustekinumab in the treatment of erythema nodosum with underlying crohn’s disease: a case report antonio sanín-guana, ba1, mark g. lebwohl, md1 1 department of dermatology, icahn school of medicine at mount sinai, new york, ny erythema nodosum (en) is a septal panniculitis characterized by raised, tender, red or purple lesions with a diameter of 1-5 cm. it is commonly treated with corticosteroids and can be an extraintestinal manifestation of crohn’s disease (cd). cd can be treated with ustekinumab, a monoclonal antibody that targets the p-40 subunit of the interleukin-12 (il-12) and interleukin-23 (il-23). a 78-year-old woman with a 25-year history of cd which required colon resection and a 55-year history of poorly controlled en presented with a chief complaint of painful bilateral lesions on her lower extremities, primarily on the right leg and dorsal feet. similar lesions had been recurring for decades. the patient had a family history of ulcerative colitis, and her cd manifestations had included occasional perianal abscess, dysphagia, and acid reflux. treatment for cd had included sulfasalazine and infliximab, and the patient failed treatments for en, including oral potassium iodide, intralesional triamcinolone acetonide 10 mg/cc, and oral colchicine. on physical examination, she had 8 tender erythematous nodules on the anterior and posterior aspects of both lower legs. at the time of the visit, the patient had been receiving only prednisone 5 mg, with minimal improvement and could not be treated with nsaids because of her cd. over the course of the next 11 months, she continued to develop intermittent nodules on both legs and feet. although the patient was not actively experiencing any other cd symptoms, the relationship of en as an extra-intestinal manifestation of cd suggested that the cd was not well controlled. as such, a new abstract erythema nodosum (en) is a septal panniculitis characterized by raised, tender, red or purple lesions with a diameter of 1-5 cm. it is commonly treated with corticosteroids and can be an extra-intestinal manifestation of crohn’s disease (cd). cd can be treated with ustekinumab, a monoclonal antibody that targets the p-40 subunit of the interleukin-12 (il-12) and interleukin-23 (il-23). a 78-year-old woman with erythema nodosum and crohn’s disease presented with multiple erythematous nodules, which had been recurring on both of her legs for decades. the patient had failed many traditional en treatments and was prescribed off-label ustekinumab, resulting in resolution of en. this finding suggests that ustekinumab may be a potential treatment for en in patients who also have cd. introduction case report skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 150 treatment to target the underlying cd could be initiated to attempt to resolve the en, so the patient was prescribed off-label ustekinumab. treatment began with a 180 mg infusion, and subsequent 90 mg subcutaneous injections on average every 6 weeks. improvement of the en lesions was first seen at 16 months, and at 17 months there was full resolution of lesions, without development of new nodules. at 24 months, the patient had only scars on the lower legs. crohn’s disease (cd) is present in 0.2% of the adult population in the united states, presenting more commonly in women than in men.1 cd can manifest itself in any part of the gastrointestinal tract and is characterized by granulomatous transmural inflammation. cd symptoms generally include fever, fatigue, and weight loss.2 in addition to its typical intestinal symptoms, cd may also be associated with extraintestinal manifestations in 6-36% of patients.2 erythema nodosum (en), the most widespread form of panniculitis (septal inflammation of subcutaneous fat tissue),8 is one such dermatological extraintestinal manifestation of cd that is present in 415% of cd patients.3 it is three to five times more prevalent in female patients than in male patients and can occur amongst all age groups, although it generally is manifested in between the second and fourth decades of life.8 en is an inflammatory process that involves subcutaneous fat lobules,6 which cause raised, tender, red or purple lesions with a diameter of 1-5 cm,8 generally found on the anterior extensor surface of the lower extremities.4,5 en can be attributed to many different factors and may be idiopathic in up to 50% of cases,7 although in 1-4% of cases it may be caused by enteropathies, such as cd.8 a strong correlation exists between the presence of en and intestinal disease activity. there are some reports that en in patients with cd is associated with the t-cell immune response to common antigens of intestinal and skin bacteria. the presence of anca and hla-b27 antigen in patients with en and ibd also argues in favor of the important role of genetic factors.8 en is usually treated with corticosteroids and intensification of medical therapy to control intestinal disease.5 ustekinumab is a monoclonal antibody that targets the p-40 subunit of the interleukin-12 (il-12) and interleukin-23 (il-23).9 it is approved by the fda to treat moderate to severe plaque psoriasis and psoriatic arthritis, in addition to cd and uc.11 inflammation of the gastrointestinal tract in cd patients has been associated with a th1-type response; ustekinumab has been suggested to inhibit differentiation of th1 cells in patients with cd. in addition, il-12 and il-23 have been implied in the differentiation of t follicular helper cells (tfh) in the pathogenesis of cd, and it has been suggested that ustekinumab therapy also affects tfh differentiation.10 in the literature, there is one other case reported of a 43-year-old female also affected with cd and en, who was treated with ustekinumab and experienced a total remission of her en symptoms after 12 weeks of treatment.12 this is a case in which ustekinumab was effective in treating en in a patient with concomitant cd. this suggests that the inhibition of the il-12 and il-23 pathways in patients with cd may also be responsible for decreasing the inflammatory response discussion conclusion skin march 2022 volume 6 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 151 observed in en. as such, ustekinumab may present itself as a potential treatment for en in patients who also have cd. however, more research needs to be done to examine this relationship and to evaluate the safety and efficacy of ustekinumab in treating any cases of en, regardless of cause. conflict of interest disclosures: mark lebwohl is an employee of mount sinai and receives research funds from: abbvie, amgen, arcutis, avotres, boehringer ingelheim, cara therapeutics, dermavant sciences, eli lilly, incyte, janssen research &amp; development, llc, ortho dermatologics, regeneron, and ucb, inc., and is a consultant for aditum bio, almirall, altrubio inc., anaptysbio, arcutis, inc., arena pharmaceuticals, aristea therapeutics, arrive technologies, avotres therapeutics, biomx, brickell biotech, boehringeringelheim, bristol-myers squibb, cara therapeutics, castle biosciences, corevitas, dermavant sciences, dr. reddy’s laboratories, evelo biosciences, evommune, inc., facilitatation of international dermatology education, forte biosciences, foundation for research and education in dermatology, helsinn therapeutics, hexima ltd., leo pharma, meiji seika pharma, mindera, pfizer, seanergy, and verrica. funding: none corresponding author: mark lebwohl, md icahn school of medicine at mount sinai 5 e. 98th st., new york, ny 1029 email: lebwohl@aol.com references: 1. wilkins t, jarvis k, patel j. diagnosis and management of crohn's disease. am fam physician. 2011;84(12):1365-1375. 2. jumani l, kataria d, ahmed mu, shah maa, raja k, shaukat f. the spectrum of extra-intestinal manifestation of crohn's disease. cureus. 2020;12(2):e6928. published 2020 feb 10. doi:10.7759/cureus.6928 3. annese v. a review of extraintestinal manifestations and complications of inflammatory bowel disease. saudi j med med sci. 2019;7(2):66-73. doi:10.4103/sjmms.sjmms_81_18 4. vavricka sr, schoepfer a, scharl m, lakatos pl, navarini a, rogler g. extraintestinal manifestations of inflammatory bowel disease. inflamm bowel dis. 2015;21(8):1982-1992. doi:10.1097/mib.0000000000000392 5. fleisher m, marsal j, lee sd, et al. effects of vedolizumab therapy on extraintestinal manifestations in inflammatory bowel disease. dig dis sci. 2018;63(4):825-833. doi:10.1007/s10620-018-4971-1 6. weinstein m, turner d, avitzur y. erythema nodosum as a presentation of inflammatory bowel disease. cmaj. 2005;173(2):145-146. doi:10.1503/cmaj.050201 7. faulkes re. upper limb erythema nodosum: the first presentation of crohn's disease. clin case rep. 2014;2(5):183-185. doi:10.1002/ccr3.87 8. chowaniec m, starba a, wiland p. erythema nodosum review of the literature. reumatologia. 2016;54(2):79-82. doi:10.5114/reum.2016.60217 9. feagan bg, sandborn wj, gasink c, et al. ustekinumab as induction and maintenance therapy for crohn's disease. n engl j med. 2016;375(20):1946-1960. doi:10.1056/nejmoa1602773 10. globig am, sommer np, wild k, et al. ustekinumab inhibits t follicular helper cell differentiation in patients with crohn's disease. cell mol gastroenterol hepatol. 2021;11(1):1-12. doi:10.1016/j.jcmgh.2020.07.005 11. ustekinumab. package insert. janssen pharmaceutical companies; 2020. 12. spagnuolo r, dastoli s, silvestri m, et al. antiinterleukin 12/23 in the treatment of erythema nodosum and crohn disease: a case report. dermatol ther. 2019;32(2):e12811. doi:10.1111/dth.12811 mailto:lebwohl@aol.com microsoft word 15. 655 proof done.docx skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 85 brief articles a case report of chilblain lupus erythematosus in a young male with literature review azib shahid md,1 katherine glaser md,2 anthony fernandez md2 1rosalind franklin university, north chicago, illinois 2cleveland clinic, cleveland, ohio chilblain lupus erythematosus (chle) is a rare, chronic, skin disorder considered a form of chronic cutaneous lupus erythematosus. patients with chle have skin lesions that are clinically consistent with chilblains and clinical or laboratory features of cutaneous or systemic lupus erythematosus. ages at onset of chilblain lupus erythematosus varies from 26 to 73 years, with a female-to-male ratio of 3:2. the diagnosis of chle was first described in 1888 by jonathan hutchinson.1 according to a comprehensive literature review published in 2008, only about 70 cases have been reported since.2 skin findings of chle consist of erythematous to violaceous papules, plaques, or nodules. initially they may be described as pruritic but eventually become painful.2-6 the lesions appear during cold or damp periods and do not remit during warmer seasons.3 cutaneous lesions occur predominately on acral surfaces and sites exposed to cold such as the nose, ears, elbows, and knees. isolated involvement of the 5th digits has been described.2,4,7 fissural hyperkeratosis and central ulceration may introduction chilblain lupus erythematosus (chle), also known as hutchinson lupus, is rare form of chronic cutaneous lupus erythematosus. the diagnosis is made in patients with clinical findings of chilblains in conjunction with the clinical or laboratory features of cutaneous or systemic lupus erythematosus (sle). similar to idiopathic chilblains (or perniosis), chle presents with tender, reddish-blue papules, nodules, or plaques on the toes, fingers, nose, or ears which are precipitated by cold exposure. there is a variation in lab findings that become positive in these patients ranging from a positive antinuclear antibody (ana), rheumatoid factor (rf), ssa/ro autoantibodies. anemia, hypocomplementemia, other autoantibodies and elevated esr have also been described in numerous patients. sporadic disease commonly affects middle-aged women whilst familial disease manifests in childhood. we report herein, a case of chle in a young male with no family history of lupus and a negative ana on initial evaluation. there is little in the published literature on chle. this case report serves to revisit the diagnosis of chle and review the existing literature. clinicians should understand the importance of early diagnosis and prompt treatment initiation in order to reduce associated morbidity and possible disfigurement. abstract skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 86 occur in lesions. nailfold capillaroscopy typically reveals changes in proximal nailfold capillary morphology, with enlarged and tortuous capillary loops being a common finding.4,5 chilblain lesions may also be accompanied by discoid or subacute cutaneous lupus erythematosus lesions. the etiology of this disorder may be familial or sporadic. a missense mutation in the trex1 gene which encodes for 3’-5’ repair exonuclease enzyme has been described in familial cases. trex1 deficiency was shown to cause intracellular accumulation of singlestranded dna which may originate from dna repair processes or the life cycle of endogenous retro-elements. it is thought that recognition of these inappropriately accumulated nucleic acids by the innate immune system leads to a type i ifn response that subsequently induces autoimmunity. this variant is characterized by onset of lesions early in infancy or adolescence.2 the pathogenesis of the sporadic form remains unknown. hypotheses have speculated a disorder of peripheral circulation resulting in either inappropriate vasoconstriction or microvascular injury associated with capillary bed occlusion, hyperviscosity, and stasis. platelet adhesiveness and aggregation are increased by cold and may contribute by promoting sluggish blood flow. common associations like hypergammaglobulinemia and rheumatoid factor may favor hyperviscosity. some reports also note an association with antiphospholipid antibody syndrome, suggesting hypercoagulability may also play a role. in support of this hypothesis, angiomri studies in at least one patient revealed reduced phalangeal perfusion.2 a peripheral circulation disorder could explain why some cohorts have significantly higher incidence of raynaud's phenomenon. to help delineate chle from other coldinduced dermatoses, the mayo clinic has proposed a useful diagnostic criteria.8 using the mayo clinic diagnostic criteria the diagnosis of chle can be made if two major and at least one minor criteria are met. these include: major criteria: 1) acral skin lesions associated with cold temperature 2) evidence of lupus erythematosus in skin lesions on histopathology or direct immunofluorescence minor criteria: 1) coexistence of systemic lupus erythematosus or other skin lesions of discoid lupus erythematosus 2) response to anti-lupus erythematosus therapy 3) negative results of cryoglobulin and cold agglutinin studies. treatments for chle include antimalarial agents, prednisone, pentoxifylline, nifedipine, and dapsone are reported to be beneficial. behavioral modifications should also be instituted including sun protection, avoidance of cold, and smoking cessation. acupuncture, yoga, and meditation have also shown to be beneficial in some cases. acupuncture however should not be used in children.3,8 a 27 year old male presented to the dermatology department with a 10 year history of a painful purpuric rash and few ulcerations on the bilateral hands, elbows, face, ears, and extensor surfaces of knees. lesions worsened with cold temperatures and stress. associated symptoms included fatigue, subjective weight loss, intermittent arthralgias, subjective fevers, and raynaud’s phenomenon. otherwise review of systems case presentation skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 87 was negative. he was previously diagnosed with discoid lupus erythematosus and treated as such with hydroxychloroquine and topical steroids with some improvements. hydroxychloroquine was subsequently discontinued due to intolerable gastrointestinal symptoms thus his presentation for additional treatment options. the patient’s history is significant for known idiopathic thrombocytopenic purpura diagnosed at age 12. after treatment with intravenous immunoglobulin, systemic steroids, and later rituximab he has since remained in remission. ongoing mild leukopenia and thrombocytopenia are being monitored by his hematologist. family history was remarkable for scleroderma in his mother. no other contributory history was identified. on examination he had multiple red to violaceous papules and plaques with few central erosions and overlying hemorrhagic crust on the nose, medial cheeks, antihelices, dorsal hands, dorsal fingers over joint spaces, anterior knees, and palmar surfaces of the fingers and toes (figures 1-4). few small smooth alopecic patches on the parietal scalp were noted. multiple atrophic hypopigmented macules were seen scattered over the upper back. mucosal surfaces were not affected. prior to presentation his laboratory work-up showed a minimally elevated double stranded dna autoantibody level but was otherwise unremarkable. work-up included an antinuclear antibody (ana), extractable nuclear antigen autoantibody panel (ena), cryoglobulin levels, complement three and four levels, serum protein electrophoresis, urinalysis, hepatitis panel, hypercoagulability panel, and a specific myositis panel to screen for dermatomyositis. repeat laboratory workup during his visit now showed positive ana and positive anti-chromatin autoantibody with chronic mild leukopenia and thrombocytopenia. the remaining ena panel was negative and notably cold agglutinins were within normal limits. outside skin biopsy reports could not be obtained so a repeat punch biopsy was performed from the patient’s right knee. the specimen revealed focal areas of parakeratosis within the stratum corneum and focal vacuolar interface changes with scattered necrotic keratinocytes in the epidermis. within the dermis a superficial and deep perivascular and peri-eccrine lymphocytic infiltrate was identified. mucin was also present throughout the interstitial space (figures 5,6). the above histopathologic features in combination with the clinical presentation were deemed compatible with the diagnosis of chilblains lupus. our patient was advised on proper preventative measures. treatment was initiated with topical clobetasol 0.05% ointment, low dose amlodipine 2.5mg daily, pentoxifylline 400mg three times daily, and chloroquine 250mg once daily given his prior side effects with hydroxychloroquine. he plans to follow up with our dermatology department for further monitoring. figure 1. hands before skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 88 figure 2. hands after figure 3. left foot before figure 4. left foot after figure 5. biopsy 4x figure 6. biopsy 40x chilblains (also known as. pernio or perniosis) is a condition characterized by the development of cold-induced erythrocyanotic skin lesions. the word "chilblains" may be derived from the old english words "chill" and "blegen" (sore).2 literature on chle describes association of this disorder with several other conditions that are discussed below. so we recommend a thorough evaluation of all presenting signs and symptoms, a detailed family history, comprehensive lab evaluation and early diagnosis which are the cornerstones in the management of this disorder. discussion skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 89 chilblain lupus is relatively uncommon. in a cohort of 308 patients with cutaneous lupus, chilblain lupus was found in only 9.3% of females and 1% of males.6 women seem to be predominantly affected, but this may reflect higher general tendency for women to be affected by lupus erythematosus. ana is typically positive and tends to be a speckled-pattern.7 at least one study suggested presence of ssa/ro autoantibodies were significantly common in chilblain lupus patients.5 in other studies, however, only a minority of patients have ssa/ro autoantibodies.3,4,8,9 hypergammaglobulinemia is observed >66% patients and rheumatoid factor is present in∼50%.2,4,7 anemia, hypocomplementemia, other autoantibodies and elevated esr have also been described in numerous patients.3,7 pancytopenia in association with chilblain lupus has been rarely described.10 chle is associated with presence or progression to sle in about 18-20% of patients, and chilblain lupus lesions may occur prior, concurrently, or subsequent to sle diagnosis.5,2 in general, sle patients with chilblain lupus lesions tend to have relatively mild systemic involvement and low prevalence of renal involvement.1 approximately 25 percent of patients who present with chilblains meet classification criteria for sle, and additional patients (5 to 6 percent in one study) may fulfill sle criteria subsequently. observations from a series of 33 patients with chilblains that included patients with chilblain lupus erythematosus suggest that persistence of skin lesions beyond cold seasons may be more frequent in patients with chilblain lupus erythematosus.3 this was also observed in our patient. the most frequently reported and most studied relationship between chilblains and another disease is the relationship between chilblains and lupus erythematosus. multiple reports describe the development of skin lesions that are clinically consistent with chilblains in patients with clinical or laboratory evidence of cutaneous lupus erythematosus or systemic lupus erythematosus.2-7 less commonly reported association includes pregnancy induced chilblain lupus.11 an association with anorexia, intestinal lymphoma and chronic myelomonocytic leukemia has also been reported but not conclusively proven.12-14 according to the literature, it is not completely apparent whether all reported patients had normal values for cryoglobulins, cold agglutinins and cryofibrinogens in chilblains lupus.15 all these values were found to be negative in our patient. histology is typically characterized by a superficial and deep perivascular lymphocytic infiltrate. vacuolar interface changes are also seen in many lesions. dif may reveal deposition of immunoglobulins, complement, or a lupus band at the dermalepidermal junction.12 the main differential diagnosis is with idiopathic chilblains or perniosis. studies suggest histologic findings that may favor chle include spongiosis (not observed in le), vacuolation of the basal cells (more frequent in le), perieccrine inflammation (uncommon in le), and presence of dermal edema (much more frequent in idiopathic chilblains).9,16 numerous studies have particularly stressed absence of perieccrine inflammation in chle compared to idiopathic chilblains.9,16 necrotic keratinocytes and vacuolar change can be seen in idiopathic chilblains. 9,16 these distinguishing features have not been found in all studies and distinction based only on histopathology is not always possible. diagnosis should be correlated with clinical and serologic data. a clinical review by su wp et al. that reviewed 5 patients and developed the diagnostic criteria discussed skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 90 earlier concluded that chilblain lupus erythematosus lesions are slower to respond to treatment compared to discoid lupus erythematosus. treatment with antimalarial agents, prednisone, pentoxifylline, or dapsone was found to be beneficial in their patients.8 other treatment options include protection from cold by physical measures and the use of oral or topical antibiotics if the lesions get infected. we used calcium channel blockers and topical steroids in our patient which proved to be effective in clearing out the skin lesions. efficacy of nifedipine (a calcium channel blocker) for treating chilblains is evident in literature.17 chilblain lupus erythematosus is a rare diagnosis that can be difficult to make. it is important to rule out other cold induced syndromes prior to initiating therapy. chilblain lupus is persistent, thus once lesions have developed they may take 4 to 6 months to resolve. all patients newly diagnosed with chle should be counseled on the specific disease course, including any potential risk for scarring and disfigurement and should be reassured that their disease progression is relatively benign. in a patient diagnosed with chilblain lupus, the treatment goal is to prevent development of new lesions and expedite the healing of current lesions in order to avoid discomfort and scarring. all patients should be encouraged to stop smoking and begin a smoking cessation program. the risk of developing sle in patients with chle is approximately 18% so regular follow up with clinical/laboratory investigations to look for progression to sle is very important. keywords: chilblain, pernio, cutaneous lupus erythematosus, raynaud’s phenomenon, chle conflict of interest disclosures: none funding: none corresponding author: azib shahid md affiliation: rosalind franklin university, north chicago, illinois address: 2537 meridian drive, great lakes, illinois, 60088 tel: 773-822-8617 email: azibshahid@gmail.com references: 1) hutchinson j. harveian lectures on lupus. br med j. 1888 jan 14;1(1411):58-63. 2) hedrich cm, fiebig b, hauck fh, et al. chilblain lupus erythematosus--a review of literature. clin rheumatol. 2008 aug;27(8):949-954. 3) viguier m, pinquier l, cavelier-balloy b, et al. clinical and histopathologic features and immunologic variables in patients with severe chilblains. a study of the relationship to lupus erythematosus. medicine (baltimore). 2001 may;80(3):180-188. 4) doutre ms, beylot c, beylot j, et al. chilblain lupus erythematosus: report of 15 cases. dermatology. 1992;184(1):26-28. 5) franceschini f, calzavara-pinton p, quinzanini m,et al.. chilblain lupus erythematosus is associated with antibodies to ssa/ro. lupus. 1999;8(3):215-219. 6) vera-recabarren ma, garcia-carrasco m, ramos-casals m, et al. cutaneous lupus erythematosus: clinical and immunological study of 308 patients stratified by gender. clin exp dermatol. 2010 oct;35(7):729-735. 7) millard lg, rowell nr. chilblain lupus erythematosus (hutchinson). a clinical and laboratory study of 17 patients. br j dermatol. 1978 may;98(5):497-506. 8) su wp, perniciaro c, rogers rs 3rd, et al. chilblain lupus erythematosus (lupus pernio): clinical review of the mayo clinic experience and proposal of diagnostic criteria. cutis. 1994 dec;54(6):395-399. conclusion skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 91 9) boada a, bielsa i, fernandez-figueras mt, et al. perniosis: clinical and histopathological analysis. am j dermatopathol. 2010 feb;32(1):19-23. 10) lavigne c, mailot f, machet l, et al. lethal pancytopenia associated with chilblain lupus erythematosus. acta derm venereol. 2000 sepoct;80(5):393. 11) stainforth j, goodfield mj, taylor pv. pregnancy-induced chilblain lupus erythematosus. clin exp dermatol. 1993 sep;18(5):449-451. 12) marks r, baker h, marten rh, et al. chilblain lupus erythematosus as a manifestation of lymphoma. proc r soc med. 1967 may; 60(5):494–496 13) kelly jw, dowling jp. pernio. a possible association with chronic myelomonocytic leukemia. arch dermatol. 1985 aug;121(8):10481052. 14) white kp, rothe mj, milanese a, et al.. perniosis in association with anorexia nervosa. pediatr dermatol. 1994 mar;11(1):1-5. 15) belizna cc, tron f, joly p, et al. outcome of essential cryofibrinogenaemia in a series of 61 patients. rheumatology (oxford) 2008 feb;47(2):205-207 16) cribier b, djeridi n, peltre b, et al.. a histologic and immunohistochemical study of chilblains. j am acad dermatol. 2001 dec;45(6):924-929. 17) rustin mh, newton ja, smith np et al. the treatment of chilblains with nifedipine: the results of a pilot study, a double-blind placebo-controlled randomized study and a long-term open trial. br j dermatol. 1989 feb;120(2):267-275. skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 640 skinmages syringofibroadenomas of the bilateral lower extremities jordan bury, do1, sean igelman, md2, h nicholas shamma, md2,3, julian trevino, md2 1primary care-family health, wpafb, wright patterson, oh 2wright state university school of medicine, department of dermatology, fairborn, oh 3american dermatopathology laboratory, centerville, oh a 52-year-old man presented to clinic with a one-year history of asymptomatic lesions located on his bilateral lower legs (figure a). he reported that occasionally these lesions “pop open”, bleed, and become painful. he denied scratching the lesions. no prior or current treatments have been used. the patient has cerebral palsy and is wheelchair bound. a shave biopsy was performed (figure b). the biopsy showed thin anastomosing epithelial cords and strands extending from the epidermis and forming a lattice. rare ductal structures were noted within the thin cords. there was underlying dermal fibrosis with thickened and increased fibrocytes, and a proliferation of thin-walled blood vessels. the anastomoses of the thin epithelial cords with underlying fibrovascular stroma supported the diagnosis of syringofibroadenoma. syringofibroadenoma is a rare adnexal tumor that arises from the acrosyringial cells of the eccrine ducts. the tumor was first described in 1963 by mascaro, with only 75 cases reported to date.1 while the clinical presentation is variable and nonspecific, definitive diagnosis can be made using histopathology. syringofibroademoma is more commonly seen in elderly individuals in their seventh a b skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 641 and eighth decade of life with the majority of the lesions located on the extremities, most commonly acral sites.2 although it does not have a clear racial or age predilection, it has been associated with schopf-schulzpassarge syndrome, clouston syndrome, and leprosy.1,3, 4 this neoplasm has also been reported to present in conjunction with other dermatological disorders most commonly chronic stasis dermatitis.5 syringofibroadenoma can present as a plaque, papule, or nodule. it is typically a solitary lesion but can also be multiple. the lesions tend to be slow-growing and have the potential to spread over large areas of the body.1, 3 eccrine syringofibroadenoma is classified into five subtypes: (1) solitary, (2) multiple with hidrotic ectodermal dysplasia, (3) multiple without associated cutaneous findings, (4) nevoid, and (5) reactive.2 the histopathology described above is shared among all subtypes. due to the variable nature of this tumor, it can be easily misdiagnosed or mismanaged. histopathology allows for confirmation of the disorder due to the distinct histopathological presentation.5 differential diagnoses includes poroma which, while sharing the histogenesis, does not contain the corded epithelium found in syringofibroadenoma. fibroepithelioma of pinkus has a similar pathologic appearance, but lacks the ductile formation within the cords, and has basaloid differentiation. early kaposi sarcoma shows staghorn, ectatic, lymphatic-like vessels, and plasma cells, while late ks has a busy dermis surrounding adnexal structures and preexisting vessels with positive promontory sign. in this case, the patient most likely developed reactive syringofibroadenomas from his chronic stasis. he was treated with compression and close follow-up. reported treatment options included excision for solitary lesions, cryotherapy, curettage, electrodessication, radiotherapy and etretinate topical therapy.2 it is considered to be a benign condition, though there have been cases reported of malignant transformation into syringofibrocarcinoma and eccrine porocarcinoma.5 for this reason, it is appropriate to excise or follow the lesions to monitor progression. conflict of interest disclosures: none funding: none corresponding author: jordan bury, do 4881 sugar maple dr wright-patterson afb, oh 45433 phone: (614) 795-3411 email: jordanbury3@gmail.com references: 1. tey, h. l., et al. “leprosy-associated eccrine syringofibroadenoma of mascaro.” clinical and experimental dermatology, vol. 32, no. 5, 2007, pp. 533–535., https://doi.org/10.1111/j.13652230.2007.02434.x. 2. bottino, caroline bertolini, et al. “solitary eccrine syringofibroadenoma case report.” anais brasileiros de dermatologia, vol. 90, no. 3 suppl 1, 2015, pp. 235–238., https://doi.org/10.1590/abd1806-4841.20153802. 3. andrade, ana carolina, et al. “clouston syndrome associated with eccrine syringofibroadenoma.” anais brasileiros de dermatologia, vol. 89, no. 3, 2014, pp. 504–506., https://doi.org/10.1590/abd1806-4841.20142837. 4. riera‐monroig, josep, et al. “eccrine syringofibroadenoma as a clue for the diagnosis of schöpf‐schulz‐passarge syndrome in acquired palmoplantar keratoderma.” journal of cutaneous pathology, vol. 47, no. 10, 2020, pp. 987–989., https://doi.org/10.1111/cup.13743. 5. bjarke, torsten, et al. “carcinoma and eccrine syringofibroadenoma: a report of five cases.” journal of cutaneous pathology, vol. 30, no. 6, 2003, pp. 382–392., https://doi.org/10.1034/j.16000560.2003.00072.x. skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 602 brief article predicting skin cancer development after liver transplant chelsea shope, mscr1, laura andrews, mscr1, courtney linkous, ba1, pelin sagut, md2, lara wine lee, md, phd2 1college of medicine, medical university of south carolina, charleston, sc 2department of dermatology & dermatologic surgery, medical university of south carolina, charleston, sc increases in sot recipients (sotr) 1and post-transplant survival have increased the number of patients affected by chronic immunosuppression. sequalae includes increased risk for malignancies, most commonly skin cancer.2 risk of skin cancer is correlated with type of organ transplanted,3 however, the majority of literature elucidating skin cancer risk is in kidney recipients.4 while liver recipients is reported as lowest risk for skin cancer, there is less data compared to kidney graft recipients, and the incidence rates reported are wide.5 we sought to describe the incidence and associated risk factors for skin cancer in liver transplant recipients at our institution. further characterizing skin cancer incidence in this abstract introduction: as the number of solid organ transplants (sots) continues to increase and post-transplant therapies improve, sot recipients (sotrs) live longer and thus, are increasingly affected by post-transplant sequala such as skin cancer. research investigating risk factors associated with skin cancer development in sotrs has largely been conducted in kidney recipients. methods: we performed a retrospective chart review of sotrs seen by dermatology from january 1, 2012 – june 1, 2022. patients were referred due to specific skin complaints or for concerning lesions. data was analyzed using pearson chi-square testing and classification and regression tree (cart) modeling. results: of 530 patients meeting inclusion criteria, 80 received liver transplants. among liver recipients, a total of 155 skin cancers and five recurrences developed following transplant among 37 patients (46.3%) with skin cancer diagnosis occurring within a mean of 3.6 years. 35 (94.6%) were caucasian and the remaining two were african american. patients who developed skin cancer were significantly more likely to be male (78.4%, pvalue=0.045) and former smokers (59.5%, p-value=0.038). cart showed age greater than 43 years was the biggest predictor for later skin cancer development. patients most frequently developed squamous cell carcinoma (60.9%) of the head and neck (51.4%) or upper extremities (29.7%). conclusion: risk factors associated with skin cancer development in liver transplant recipients include increased age at transplant, male sex, and smoking status. stratification of referrals to dermatology based on these factors should be considered. introduction skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 603 cohort may help risk stratify patients, allowing for efficient use of resources.6 following irb approval, we conducted a retrospective review of sotrs at our institution between january 1, 2012, and june 1, 2022. sotrs who were seen by transplant and dermatology at our institution were included. these patients were referred due to skin complaints or presence of concerning skin lesions. information regarding patient demographics, comorbid conditions, family history, transplant course, and dermatologic course were collected. data analysis was performed using spss statistics 28 (ibm, armonk, ny). descriptive statistics were used to characterize the patient population. categorical data was evaluated using pearson chi-square testing. classification and regression tree (cart) modeling was used to assess risk for skin cancer development. cart modeling adds variables of interest to the regression model in a univariate manner. variables included in cart analysis were sex, age at transplant, race, smoking status, comorbid conditions, and transplant-associated medications. cart uses significant variables to the build a multivariate regression model, as well as z counts and estimated marginal means. we identified 530 patients who underwent sot and were seen by dermatology, of which 80 received liver transplants. mean age at transplant was 52.65 years. the majority were caucasian (90.0%) and male (67.5%). half of recipients were non-smokers (table 1). among liver recipients, 37 (46.3%) developed skin cancer post-transplant, with a mean time to first skin cancer diagnosis of 3.6 years. they had a mean age of 57.7 [+7.6] years at transplant, as compared to a mean age of 47.6 [+22.8] years in liver recipients who did not develop skin cancer (p-value <0.001). skin cancer most commonly developed in males (78.4%, p-value=0.045) and former smokers (59.5%, p-value=0.038) (table 1). skin cancer occurred most frequently among caucasian patients (35, 94.6%). among african american patients who developed skin cancer (2), both patients were male, former smokers who developed bcc on the face. a total of 155 skin cancers and five recurrences developed among 37 liver recipients. first skin cancers were most frequently scc (67.6%), bcc (29.7%), or melanoma in situ (mis) (2.7%). among sccs, 44.0% were invasive at the time of diagnosis. skin cancers were most commonly found on the head and neck (51.4%, including scalp, face, ear, and neck) or upper extremities (29.7%). further characterization of these skin cancers is provided (table 2). subsequent skin cancers occurred in 23 of 37 liver recipients (62.2%) with recurrence in one patient. second skin cancers were also most commonly scc (14, 60.9%) or bcc (9, 39.1%). in total, there were 101 sccs, 49 bccs, and 5 mms. no merkel cell carcinomas, kaposi sarcomas, or porocarcinomas were reported. cart demonstrated that age greater than 43 years was the strongest predictor for later skin cancer development in this cohort. among patients less than 43 years of age, caucasian race and older age at transplant were most strongly correlated with skin cancer development. the following were not predictors of post-transplant skin cancer development: hypertension, type 2 diabetes methods results skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 604 table 1. liver transplant recipient patient demographics all liver transplant recipients liver transplant recipients with skin cancer liver transplant recipients without skin cancer p-value age at transplant (years) 52.65 57.73 47.57 <0.001* race (count, %) 0.186 african american 8 (10.0%) 2 (5.4%) 6 (14%) caucasian 72 (90.0%) 35 (94.6%) 37 (86%) sex (count, %) 0.045* female 26 (32.5%) 8 (21.6%) 18 (41.9%) male 54 (67.5%) 29 (78.4%) 25 (58.1%) smoking status (count, %) 0.031* never smoker 40 (50%) 13 (35.1%) 27 (62.8%) current smoker 4 (5%) 2 (5.4%) 2 (4.7%) former smoker 36 (45%) 22 (59.5%) 14 (32.6%) family history of skin cancer (count, %) 0.428 yes 5 (6.3%) 3 (8.1%) 2 (4.7%) no 75 (93.8%) 34 (91.9%) 41 (95.3%) *indicates statistically significant result (p < 0.05) skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 605 table 2. first skin cancers among liver transplant recipients type of skin cancer count (%) squamous cell carcinoma 25 (67.57%) sccis* 14 (56.0%) invasive+ 11 (44.0%) low risk 5 (45.45%) high risk 5 (45.45%) very high risk 1 (9.1%) basal cell carcinoma 11 (29.73%) melanoma in situ 1 (2.70%) location of skin cancer count (%) scalp 6 (16.22%) face & neck 11 (29.73%) ear 2 (5.41%) upper extremities 11 (29.73%) chest or back 2 (5.41%) lower extremities 2 (5.41%) other 3 (8.11%) *sccis: squamous cell carcinom in situ. +low risk: trunk/extremities, <2 cm or well/moderately differentiated, <6 mm deep. high risk: trunk/extremities, 2 4 cm or anywhere on head/neck. very high risk: any site >4 cm or poorly differentiated, >6 mm deep, or perineural/lymphatic involvement. skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 606 mellitus, hyperlipidemia, chronic kidney disease, cardiomyopathy or coronary artery disease, hepatitis, nonalcoholic fatty liver disease, and cirrhosis. tacrolimus, mycophenolate mofetil (mmf), azathioprine, val/acyclovir, and cyclosporine (csa) use as part of the post-transplant therapeutic regimen were not significant predictors for skin cancer, though csa use post-transplant approached significance as a risk factor for skin cancer (p-value=0.063). it is well established that sotrs are at increased risk for skin cancer. in all sotrs, the factors most associated with skin cancer development include white race, increased age at transplant, male sex, heart or lung transplant versus kidney or liver transplant, and lower fitzpatrick phototypes.2 in our cohort of liver recipients, these traits remained significant predictors of skin cancer development, with the addition of smoking status. notably, race was a significant risk factor with cart modeling, but not when chi square testing was used. in our sample, the number of non-white liver recipients that met inclusion criteria was small. it is probable that the sample size was not substantial enough for significance with chi square testing. it is suggested that heart and lung recipient risk for skin cancer is increased due to the aggressive immunotherapies that this type of transplant necessitates.3 in our liver cohort, the use of cyclosporine in post-transplant regimens was trending toward suggesting that providers may need a lower threshold for referral to dermatology for skin cancer surveillance. in general, transplant recipients are estimated to be at a 40 – 250 times increased risk for cutaneous scc and a three-fold increased risk for mm.3 while liver patients may be at less of a risk for skin cancer development as compared to other transplant types, nearly half of the patients in our cohort developed skin cancer. like other transplant types, liver recipients are most likely to develop scc, followed by bcc, and mm. skin cancers in this cohort are most common on sun exposed areas of the head, neck, and upper extremities. while no official guidelines for referral for skin cancer surveillance screening posttransplant exist, the consensus in the literature is to refer one-year post-transplant,2 especially for those patients at high-risk in our cohort, including white race, age >43 years at transplant, current or former smokers, or prescribed csa. in our cohort of liver recipients, however, skin cancer took longer to develop. future, larger scale studies in liver recipients are needed to determine the appropriate interval for dermatologic evaluation. referral stratification may alleviate burden, allowing dermatologic appointments to be given to those most at risk for serious morbidity and mortality.2 targeted interventions to educate liver recipients on their risk for skin cancer may also be useful. conflict of interest disclosures: none funding: none corresponding author: chelsea shope, mscr 135 rutledge ave., 11th floor charleston, sc 29425 phone: (843) 754-9577 email: shopec@musc.edu references: 1. 2019: record number of lives saved. united network for organ sharing. news web site. https://unos.org/news/organ-donation-setsrecord-in-2019/. published 2020. updated january 9, 2020. accessed january 5, 2021. discussion https://unos.org/news/organ-donation-sets-record-in-2019/ https://unos.org/news/organ-donation-sets-record-in-2019/ skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 607 2. jambusaria-pahlajani a, crow ld, lowenstein s, et al. predicting skin cancer in organ transplant recipients: development of the suntrac screening tool using data from a multicenter cohort study. transpl int. 2019;32(12):1259-1267. 3. garrett gl, lowenstein se, singer jp, he sy, arron st. trends of skin cancer mortality after transplantation in the united states: 1987 to 2013. j am acad dermatol. 2016;75(1):106-112. 4. acuna sa, huang jw, scott al, et al. cancer screening recommendations for solid organ transplant recipients: a systematic review of clinical practice guidelines. am j transplant. 2017;17(1):103-114. 5. bhat m, mara k, dierkhising r, watt kd. gender, race and disease etiology predict de novo malignancy risk after liver transplantation: insights for future individualized cancer screening guidance. transplantation. 2019;103(1):91-100. 6. borik l, balagula y, hinds ga, loss mj. non-melanoma skin cancers in african american solid organ transplant recipients: regional bias or a real need for surveillance? eur j dermatol. 2017;27(5):530-531. skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 254 short communication persistent papulosquamous dermatitis as an early cutaneous manifestation of celiac disease karishma daftary, ba1, raj chovatiya, md, phd1 1department of dermatology, feinberg school of medicine at northwestern university, chicago, il usa celiac disease (cd) is a gluten-induced autoimmune disorder resulting in small bowel villous atrophy and malabsorption that affects up to 1% of the united states population.1 beyond its gastrointestinal findings, cd has a broad spectrum of clinical phenotypes. here we discuss a case of chronic, refractory papulosquamous dermatitis preceding an eventual diagnosis of cd. a healthy 36-year-old woman was referred to dermatology after a one-year history of persistent, asymptomatic rash. physical exam was notable for scaly, hypopigmented papules and plaques on the abdomen and bilateral lower posterior flanks (figure 1). potassium hydroxide preparation from skin scraping was equivocal for fungal elements, but given the suggestive physical exam, an initial diagnosis of pityriasis versicolor was made. over the next six months, the patient was treated with various combinations of anti-fungals without improvement, including topical pyrithione zinc, selenium sulfide, and ketoconazole, as well as oral fluconazole and itraconazole. the rash continued to progress, now also involving the face, shoulders, upper arms, and back. punch biopsy of a lesion showed mild hyperkeratosis overlying normal stratum corneum (figure 2). periodic acid figure 1. scaly, hypopigmented plaques observed on the patient’s flank schiff staining was negative for fungi. histopathology and cutaneous exam were most consistent with a nonspecific papulosquamous dermatitis only morphologically resembling pityriasis versicolor. over the next 6 months, mid and high potency topical corticosteroids and narrowband uvb phototherapy (~50 treatments) proved to be ineffective. following an episode of left lower quadrant pain almost two years after the initial cutaneous eruption, laboratory workup was notable for an elevated tissue transglutaminase igg antibody titer. subsequent esophagogastroduodenoscopy with duodenal biopsy revealed villous skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 255 figure 2. punch biopsy of a lower back lesion demonstrating mild hyperkeratosis overlying normal stratum corneum (hematoxylin & eosin 10x). blunting and increased intraepithelial lymphocytes. the patient was diagnosed with cd and began a gluten-free diet. within the first month of her dietary changes, her dermatitis completely resolved with only mild post-inflammatory pigment alteration remaining. the incidence of skin disorders among patients with cd is estimated to be 22.6 per 1000 person-years.1 dermatitis herpetiformis (dh) is the classic cutaneous manifestation of cd, affecting ~13% of patients with the disease.2 dh presents with diffuse, pruritic vesicles and secondary crusting of excoriated lesions. other dermatologic diseases associated with cd include psoriasis, palmoplantar pustulosis, urticaria, rosacea, atopic dermatitis, and aphthous stomatitis, as well as several others with less supporting evidence.3-5 the risk of developing skin disorders is highest within the first year of cd diagnosis and may persist beyond 10 years1; however, patients may experience skin symptoms in the absence of gastrointestinal symptoms. for example, up to one-third of patients with dh exhibit symptoms at the time of cd diagnosis.2 while rare, there are reported cases of otherwise asymptomatic cd presenting with palmoplantar pustulosis, aphthous stomatitis, and dermatomyositis that have resolved with gluten-free diet.4,5 while several, well-described cutaneous eruptions have been reported with cd, the prevalence of both preceding chronic dermatoses and asymptomatic, nonspecific eruptions is unknown, particularly among those without gastroenterological symptoms. this may be due to underreporting of such rashes and/or underdiagnosis of cd. clinicians should consider a broad workup, skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 256 including cd screening, for chronic, refractory papulosquamous dermatoses, even in the absence of gastrointestinal symptoms. abbreviations used: celiac disease (cd); dermatitis herpetiformis (dh) conflict of interest disclosures: raj chovatiya has served as an advisory board member, consultant, and/or investigator for abbvie, arcutis, arena, dermavant, incyte, national eczema association, pfizer, regeneron, and sanofi-genzyme, and speaker for abbvie, eli lilly, incyte, regeneron, sanofi-genzyme, and ucb. karishma daftary has no conflicts to disclose. funding: none corresponding author: raj chovatiya, md, phd department of dermatology northwestern university feinberg school of medicine 676 n st clair st suite 1600 chicago, il 60611 raj.chovatiya@gmail.com references: 1. lebwohl b, söderling j, roelstraete b, et al. risk of skin disorders in patients with celiac disease: a population-based cohort study. j am acad dermatol. 2021;85(6):1456-64. 2. salmi tt. dermatitis herpetiformis. clin exp dermatol. 2019;44(7):728-31. 3. klemm n, gooderham mj, papp k. could it be gluten? additional skin conditions associated with celiac disease. int j dermatol. 2021. 4. muddasani s, rusk am, baquerizo nole kl. gluten and skin disease beyond dermatitis herpetiformis: a review. int j dermatol. 2021;60(3):281-8. 5. rodrigo l, beteta-gorriti v, alvarez n, et al. cutaneous and mucosal manifestations associated with celiac disease. nutrients. 2018;10(7). mailto:raj.chovatiya@gmail.com powerpoint presentation 30 20 10 0 change from baseline 6 4 2 0 2 change from baseline 20 15 10 5 0 change from baseline 20 15 10 5 0 change from baseline easi itch poem dlqi efficacy and safety of tralokinumab treatment in adults of different racial subgroups with moderate-to-severe atopic dermatitis in three randomized, placebo-controlled phase 3 trials tiffany mayo1, april armstrong2, leon kircik3, jonathan i. silverberg4, andrew blauvelt5, ben esdaile6, shannon schneider7, thomas mark8, melinda gooderham9, andrew f. alexis10 1university of alabama at birmingham, birmingham, al, usa; 2keck school of medicine of university of southern california, los angeles, ca, usa;3icahn school of medicine at mount sinai, new york, ny, usa; 4the george washington school of medicine and health sciences, washington, dc, usa; 5oregon medical research center, portland, or, usa; 6whittington health national health service foundation trust, london, uk; 7leo pharma inc., madison, nj, usa; 8leo pharma a/s, ballerup, denmark; 9skin centre for dermatology, peterborough, on, canada; 10weill cornell medicine, new york, ny, usa table 1. baseline demographic and disease characteristics of patients by racial subgroup in pooled e1/2/3 table 2. summary of aes through week 16 in ecztra 1/2/3 by racial subgroup conclusions • in this post hoc analysis, tralokinumab was well-tolerated and improved the signs and symptoms of moderate-to-severe ad, regardless of race, with further improvements up to 52 weeks of treatment • limitations of this analysis include disparate sample sizes across racial subgroups figure 1. summary of tralokinumab ecztra trials included in these analyses objective to evaluate the efficacy and safety of tralokinumab +/tcs versus placebo +/tcs, by self-identified racial subgroup (asian, black, white) in adults with moderate-tosevere ad across three phase 3 trials materials and methods patients and treatment • ecztra 1 and 2 were two identically designed, multinational, double-blind, randomized, placebo-controlled, 52-week trials (figure 1) o patients were randomized 3:1 to subcutaneous tralokinumab 300 mg or placebo every 2 weeks (q2w) for an initial 16 weeks following a 600 mg loading dose o patients who achieved iga 0/1 or easi-75 at week 16 with tralokinumab were rerandomized to tralokinumab q2w or every 4 weeks or placebo, for an additional 36 weeks o rescue treatment could be used at the discretion of the investigator to control intolerable symptoms • in ecztra 3, patients were randomized 2:1 to subcutaneous tralokinumab 300 mg + tcs as needed or placebo + tcs as needed q2w for an initial treatment period of 16 weeks following a 600 mg loading dose o patients who achieved iga 0/1 or easi-75 at week 16 with tralokinumab were rerandomized to tralokinumab q2w or every 4 weeks, with tcs as need, for an additional 16 weeks • patients self-reported their racial subgroup analyses • as shown in figure 1, data are presented as: o pooled from ecztra 1/2/3 o pooled from ecztra 1/2 o ecztra 3 • efficacy outcomes assessed were: o proportion of patients achieving easi-75, iga 0/1 o change from baseline in easi, peak pruritus nrs, dlqi, and poem • data are presented at week 16 (ecztra 1/2/3) and week 52 (ecztra 1/2) • data are presented as observed regardless of rescue medication use. multiple imputation was used for missing data • data were used as per food and drug administration (fda) label and united states prescribing information (uspi; i.e., data from 2 sites were excluded as per fda guidance) results patients, demographics, and clinical characteristics • this post hoc analysis included 1876 patients (uspi population) across ecztra 1, 2, and 3 who self-reported their race as asian, black, or white (figure 1, table 1) • baseline demographic and disease characteristics were largely balanced between treatment groups and across racial subgroups (table 1) o ad severity was more moderate in the black subgroup tralokinumab improved signs and symptoms of ad across racial subgroups at week 16 • across three pooled trials at week 16, tralokinumab significantly improved efficacy outcomes in the asian and white subgroups relative to placebo. similar results were found in the smaller black subgroup, although statistical significance was not reached for all endpoints vs placebo (figures 2-3) • lower efficacy was observed for the black subgroup relative to asian and white subgroups when the monotherapy trials were pooled, driven by higher placebo response rates. in contrast, higher efficacy was observed for the black subgroup relative to asian and white subgroups in the tcs combination trial figure 2. percentage of patients achieving easi-75 and iga 0/1 by racial subgroup at week 16 references 1. kaufman b, et al. exp dermatol 2018; 27: 340-357. 2. wollenberg a, et al. br j dermatol. 2021; 184(3)437-449. 3. silverberg j, et al. br j dermatol. 2021; 184(3)450-463 disclosures tiffany mayo has served as an investigator or consultant for eli lilly, chemocentryx, pfizer, janssen, galderma, bristol myers squibb, acelyrin, novartis, leo pharma, arcutis, and procter and gamble. april armstrong has served as a research investigator and/or scientific advisor to abbvie, almirall, arcutis, aslan, beiersdorf, bi, bms, epi, incyte, leo, ucb, janssen, lilly, nimbus, novartis, ortho dermatologics, sun, dermavant, dermira, sanofi, regeneron, pfizer, and modmed. leon kircik has served either as an investigator, consultant, or speaker for abbvie, almirall, amgen, arcutis, bausch health canada, bristol myers squibb, boehringer ingelheim, cellceutix, celgene, coherus, dermavant, dermira, eli lilly, leo, mc2, maruho, novartis, ortho dermatologics, pfizer, dr reddy's laboratories, sun pharma, ucb, taro, and xenoport. jonathan i silverberg reports honoraria as a consultant/advisory board member from leo pharma and has acted as a consultant for and/or received grants/honoraria from abbvie, anaptysbio, asana biosciences, galderma research and development, gsk, glenmark, kiniksa, leo pharma, lilly, medimmune, menlo therapeutics, pfizer, puricore, regeneron, and sanofi. andrew blauvelt has served as a speaker (received honoraria) for abbvie, arcutis, bristol-myers squibb, eli lilly and company, pfizer, regeneron, sanofi, and ucb, served as a scientific adviser (received honoraria) for abbvie, abcentra, affibody, aligos, almirall, alumis, amgen, anaptysbio, arcutis, arena, aslan, athenex, bluefin biomedicine, boehringer ingelheim, bristolmyers squibb, cara therapeutics, dermavant, ecor1, eli lilly and company, escient, evelo, evommune, forte, galderma, highlightii pharma, incyte, innoventbio, janssen, landos, leo, merck, novartis, pfizer, rapt, regeneron, sanofi genzyme, spherix global insights, sun pharma, tll pharmaceutical, trialspark, ucb pharma, vibliome, and xencor, and has acted as a clinical study investigator (institution has received clinical study funds) for abbvie, acelyrin, almirall, amgen, arcutis, athenex, boehringer ingelheim, bristol-myers squibb, concert, dermavant, eli lilly and company, evelo, evommune, galderma, incyte, janssen, leo, merck, novartis, pfizer, regeneron, sun pharma, and ucb pharma. ben esdaile has served either as an investigator, advisor or speaker for leo pharma, l’oréal, thornton & ross, bioderma, skin + me and abbvie. shannon schneider and thomas mark are employees of leo pharma. thomas mark owns leo pharma stock. melinda gooderham has been an investigator, speaker and/or advisor for: abbvie, amgen, akros, anaptysbio, aslan, arcutis, aristea, bausch health, bms, boehringer ingelheim, celgene, dermira, dermavant, eli lilly, galderma, gsk, incyte, janssen, kyowa kirin, leo pharma, medimmune, merck, meiji, moonlake, nimbus, novartis, pfizer, reistone, regeneron, roche, sanofi genzyme, sun pharma, and ucb. andrew f. alexis has received grants (funds to institution) from leo pharma, novartis, almirall, bristol myers squibb, amgen, vyne, galderma, valeant (bausch health), cara, arcutis, dermavant, abbvie, and castle; has served as an advisory board member or consultant for leo pharma, galderma, pfizer, sanofi-regeneron, dermavant, beiersdorf, ortho, l’oreal, bms, bausch health , ucb, vyne , arcutis, janssen, allergan, almirall, abbvie, sol-gel , amgen, visualdx, eli lilly, swiss american, and cutera; and a speaker for regeneron, sanofi-genzyme, pfizer, and bristol myers squibb. acknowledgements this analysis was sponsored by leo pharma a/s. medical writing according and editorial support from alphabet health by clair geary, phd was funded leo pharma a/s, ballerup, denmark, to good publication practice guidelines (https://www.ismpp.org/gpp3) scan to download a copy of this poster copies of this poster and its content, obtained through this qr code, are for personal use only and may not be reproduced without written permission from the authors introduction • atopic dermatitis (ad) is a chronic inflammatory skin disease associated with significant disease burden • although ad is highly prevalent in patients with skin of color, data on the efficacy and safety of ad therapies in these patients is limited since most clinical trials enroll predominately white patients1 o several standard measures, including easi, can underestimate ad severity in dark skin1 • tralokinumab, a specific, high-affinity interleukin-13 inhibitor, is approved in europe, canada, and the united states for the treatment of adults with moderate-to-severe ad • ecztra 1 (nct03131648), ecztra 2 (nct03160885), and ecztra 3 (nct03363854) were randomized phase 3 trials assessing the safety and efficacy of tralokinumab or tralokinumab + tcs, as needed. o ecztra 1 and 2 were placebo-controlled trials and ecztra 3 was placebo + tcs controlled the safety profile of tralokinumab treatment was consistent across racial subgroups • tralokinumab was generally well-tolerated, with a safety profile comparable to placebo and largely consistent across racial subgroups (table 2) • rates of adverse events (aes), serious aes, and aes leading to drug withdrawal were low in all treatment groups • conjunctivitis rates were lower in the asian and black relative to white subgroup (table 3) figure 4. percentage of patients achieving easi-75 and iga 0/1 by racial subgroup at week 52 (pooled monotherapy trials) improvements in efficacy outcomes beyond week 16 were consistent across racial subgroups • at week 52 (pooled monotherapy trials), easi-75 was achieved in 58% of asian patients, 66% of black patients, and 63% of white patients (figure 4) o iga 0/1 was achieved in 32% of asian patients, 38% of black patients, and 38% of white patients (figure 4) • improvements in efficacy outcomes after week 16 were also observed across racial subgroups in ecztra 3 (tcs combination trial) qr code here abbreviations adj., adjusted; ae, adverse event; ad, atopic dermatitis; dlqi, dermatology life quality index; e, number of adverse events; easi, eczema area and severity index; iga, investigator’s global assessment; n, number of patients achieving the indicated metric, or with ≥1 event; ne, number of events; np, number of patients, n, number of patients with recorded observation; nrs, numerical rating scale; pye, patient-years of exposure; q2w, every 2 weeks; sd, standard deviation; tcs, topical corticosteroids fall clinical dermatology conference, oct 20 – 23, 2022. asian n=407 black n=134 white n=1335 tralokinumab (n=291) placebo (n=116) tralokinumab (n=95) placebo (n=39) tralokinumab (n=992) placebo (n=343) mean age, y (sd) 35.2 (12.3) 32.4 (13.2) 39.3 (14.1) 38.6 (16.8) 39.0 (14.8) 38.7 (14.6) male, n (%) 176 (60.5) 76 (65.5) 38 (40.0) 20 (51.3) 578 (58.3) 209 (60.9) ethnicity, n (%) hispanic or latino 2 (0.7) 3 (2.6) 3 (3.2) 0 68 (6.9) 26 (7.6) region, n (%) north america europe australia japan asia 100 (34.4) 20 (6.9) 17 (5.8) 96 (33.0) 58 (19.9) 48 (41.4) 10 (8.6) 7 (6.0) 31 (26.7) 20 (17.2) 86 (90.5) 8 (8.4) 1 (1.1) 36 (92.3) 3 (7.7) 284 (28.6) 640 (64.5) 68 (6.9) 89 (25.9) 233 (67.9) 21 (6.1) country, n (%) united states canada japan 43 (14.8) 57 (19.6) 96 (33.0) 23 (19.8) 25 (21.6) 31 (26.7) 82 (86.3) 4 (4.2) 35 (89.7) 1 (2.6) 178 (17.9) 106 (10.7) 52 (15.2) 37 (10.8) patients with iga 3, n (%) 138 (47.4) 53 (45.7) 61 (64.2) 23 (59.0) 507/1001 (50.6) 169/346 (48.8) patients with iga 4, n (%) 153 (52.6) 63 (54.3) 33 (34.7) 15 (38.5) 490/1001 (49.0) 175/346 (50.6) mean easi (sd), n 33.2 (15.1) 34.1 (14.2) 29.2 (13.0), 94 33.1 (15.8), 38 31.5 (13.4), 997 31.9 (13.3), 344 mean scorad score (sd) 70.7 (14.7) 71.4 (12.4) 66.4 (12.4), 94 67.6 (12.7), 38 69.7 (12.8), 997 70.8 (12.8), 344 mean dlqi (sd), n 17.5 (7.1), 289 18.0 (6.6), 114 16.9 (7.1), 94 17.2 (9.7), 37 17.3 (7.0), 984 17.4 (6.9), 342 mean worst pruritus nrs (sd), n 7.8 (1.4), 288 7.8 (1.4), 116 8.1 (1.6), 94 7.7 (1.7), 37 7.7 (1.5), 991 7.9 (1.4), 342 asian black white tralokinumab (n=292) placebo (n=115) tralokinumab (n=94) placebo (n=38) tralokinumab (n=989) placebo (n=340) pye 86.93 33.60 26.92 10.74 294.47 99.54 n (%) rate (ne/100 pye) n (%) rate (ne/100 pye) n (%) rate (ne/100 pye) n (%) rate (ne/100 pye) n (%) rate (ne/100 pye) n (%) rate (ne/100 pye) all aes 197 (67.5) 570.5 79 (68.7) 633.9 52 (55.3) 542.3 25 (65.8) 512.1 713 (72.1) 753.2 243 (71.5) 772.5 serious aes 6 (2.1) 6.9 1 (0.9) 2.9 2 (2.1) 7.4 3 (7.9) 27.9 25 (2.5) 8.8 13 (3.8) 17.0 severity 161 (55.1) 424.4 61 (53.0) 455.3 45 (47.9) 408.6 17 (44.7) 316.5 590 (59.7) 500.9 181 (53.2) 412.9 mild moderate 76 (26.0) 132.2 42 (36.5) 157.7 19 (20.2) 122.5 13 (34.2) 167.6 362 (36.6) 224.4 149 (43.8) 311.4 severe 11 (3.8) 13.8 5 (4.3) 20.8 3 (3.2) 11.1 2 ( 5.3) 27.9 56 (5.7) 27.8 31 (9.1) 48.2 leading to withdrawal from trial 7 (2.4) 8.0 5 (4.3) 17.8 5 (5.3) 26.0 1 (2.6) 9.3 20 (2.0) 8.1 8 (2.4) 11.0 outcome not recovered/not resolved 39 (13.4) 65.5 18 (15.7) 65.4 14 (14.9) 55.7 7 (18.4) 74.4 156 (15.8) 70.3 43 (12.6) 60.2 recovering/resolving 16 (5.5) 18.4 8 (7.0) 23.8 7 (7.4) 26.0 41 (4.1) 15.6 21 (6.2) 26.1 recovered/resolved 179 (61.3) 483.1 68 (59.1) 544.6 49 (52.1) 445.7 22 (57.9) 428.3 668 (67.5) 655.4 233 (68.5) 680.1 recovered/resolved with sequelae 3 (1.0) 3.4 1 (1.1) 3.7 14 (1.4) 4.7 2 (0.6) 3.0 unknown 2 (2.1) 11.1 1 (2.6) 9.3 20 (2.0) 7.1 3 (0.9) 3.0 week 52 (ecztra 1+2) asian black white tralokinumab q2w (n=292) placebo (n=115) tralokinumab q2w (n=94) placebo (n=38) tralokinumab q2w (n=989) placebo (n=340) n (%) rate (ne/100 pye) n (%) rate (ne/100 pye) n (%) rate (ne/100 pye) n (%) rate (ne/100 pye) n (%) rate (ne/100 pye) n (%) rate (ne/100 pye) all aes 197 (67.5) 570.59 79 (68.7) 633.90 52 (55.3) 542.36 25 (65.8) 512.12 713 (72.1) 753.21 243 (71.5) 772.59 infections and infestations 87 (29.8) 141.50 40 (34.8) 196.42 27 (28.7) 133.73 12 (31.6) 139.67 446 (45.1) 237.71 145 (42.6) 232.08 viral upper respiratory tract infection 28 (9.6) 35.66 9 ( 7.8) 29.76 8 (8.5) 37.15 4 (10.5) 46.56 191 (19.3) 80.14 55 (16.2) 72.34 conjunctivitis 5 (1.7) 5.75 1 ( 0.9) 2.98 3 (3.2) 14.86 1 (2.6) 9.31 79 ( 8.0) 31.24 9 (2.6) 9.04 upper respiratory tract infection 17 (5.8) 21.86 6 ( 5.2) 20.83 3 (3.2) 11.14 2 (5.3) 18.62 60 (6.1) 22.07 15 (4.4) 15.07 skin infection 2 (0.7) 3.45 2 ( 1.7) 5.95 1 (1.1) 3.71 1 (2.6) 9.31 14 (1.4) 5.09 10 (2.9) 10.05 herpes simplex 5 (1.7) 8.05 1 ( 0.9) 2.98 1 (1.1) 3.71 17 (1.7) 6.45 4 (1.2) 5.02 figure 3. change from baseline in easi, itch, poem, and dlqi by racial subgroup at week 16 asian; tralokinumab asian; placebo black; tralokinumab black; placebo white; tralokinumab white; placebo ecztra 1+2+3 ecztra 1+2 ecztra 3 asian; tralokinumab black; tralokinumab white; tralokinumab asian; placebo black; placebo white; placebo ecztra 1+2+3 ecztra 1+2 ecztra 3 table 3. summary of selected aes by soc and preferred term through week 16 in ecztra 1/2/3 by racial subgroup 52 weeks ecztra 1 tralokinumab monotherapy trials tralokinumab + tcs combination trial 32 weeks ecztra 1+2+3 pooled ecztra 1+2 pooled ecztra 3 only ecztra 3 selfreported raceecztra 2 asian (n=407) black (n=134) white (n=1335) further details of these trials have been previously reported2,3 asian (n=366) black (n=99) white (n=1059) asian (n=41) black (n=35) white (n=276) ecztra 1 (n=802) ecztra 2 (n=794) ecztra 3 (n=380) total randomized ecztra 1 (n=798) ecztra 2 (n=770) ecztra 3 (n=368) uspi population week 16 error bars show standard error. easi75 iga 0 / 1 0 20 40 60 80 63 38 66 38 58 32 r e s p o n d e rs , % asian black white 0 20 40 60 80 responders, % 0 10 20 30 40 50 responders, % easi75 iga 0/ 1 https://www.ismpp.org/gpp3 powerpoint presentation efficacy of tirbanibulin ointment 1% across different patient populations: pooled results from two phase 3 studies methods • post-hoc pooled analysis from two identical phase iii, randomized, double-blinded, vehiclecontrolled studies in adults with ak on the face or scalp. eligible subjects with 4-8 clinically visible ak lesions in a 25 cm2 area were randomized 1:1 to tirbanibulin ointment 1% or vehicle (once-daily self-application for 5 consecutive days). • the primary efficacy and key secondary endpoints were complete clearance (cc, 100% reduction from baseline) and partial clearance (pc, ≥75%) rates of ak lesions at day 57. logistic regression models to find independent predictors of cc and pc of ak lesions among tirbanibulin-treated patients were built. • safety was also assessed, including adverse events (aes) and local skin reactions (lsrs: erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, erosion/ulceration; 4point grading scale: 0 [absent] to 3 [severe]). synopsis • tirbanibulin 1% ointment is indicated for the topical treatment of actinic keratosis (ak) of face or scalp based on the results of two phase 3 studies1. • tirbanibulin ointment 1% applied once-daily for 5 days was generally well tolerated and effective. previous ak treatment, fitzpatrick skin type or bmi were not predictive for the clinical response. in contrast, ak location on the face and fewer number of lesions at baseline were predictors of treatment success after 2 months. conclusions 2021 fall clinical dermatology conference for pas & nps table 1. baseline characteristics ak, actinic keratosis; sd, standard deviation. tirbanibulin (n=353) vehicle (n=349) age (years), mean (sd) 69.3 (8.6) 70.2 (9.1) gender (male), n (%) 305 (86) 304 (87) race (white), n (%) 352 (>99) 348 (>99) fitzpatrick skin type, n (%) type i 49 (14) 38 (11) type ii 200 (57) 224 (64) type iii 88 (25) 79 (23) type iv-vi 16 (5) 8 (2) ak lesion count, median (min max) 6.0 (4 8) 6.0 (4 8) objective • this post-hoc analysis aimed at assessing the efficacy of tirbanibulin in different patient subgroups by body mass index (bmi), fitzpatrick skin type and previous ak treatment. brian berman1, adrià gual2, ayman grada3, emilio fumero4, laura padullés5, francisco hernández4 1 department of dermatology and cutaneous surgery, university of miami miller school of medicine, florida, usa; 2 hospital quiron salud, barcelona, spain; 3 almirall, malvern, pa, usa; 4 almirall, sant feliu de llobregat, spain; 5 almirall, barcelona, spain • phase iii studies were funded by athenex. post-hoc analysis/medical writing was funded by almirall. • w riting support was provided by tfs healthscience. acknowledgements bb has served as a consultant, speaker, and/or investigator for almirall, biofrontera, leo and pierre-fabre, and also participated in the us biofrontera pdt advisory council; agu has served as a consultant for almirall; agr, ef, lp and fh are employees of almirall. conflicts of interest 1) blauvelt a et al. new engl j med 2021;384:512-20. 2) olsen ea et al. j am acad dermatol 1991;24:738-43. references • eligible subjects were randomized to tirbanibulin (n=353) or vehicle (n=349). over 99% of subjects completed treatment. baseline characteristics are shown in table 1. results figure 1. evolution of facial ak lesions in patients who showed complete clearance with tirbanibulin at day 29 (a) and day 15 (b) a) b) grading of lesions according to the olsen classification2 was performed post-hoc, and therefore was based on visual inspection only. ak, actinic keratosis; d, day; lsr, local skin reaction; og, olsen grade. a) the patient was a white (fitzpatrick iii), 71 year-old female. previous dermatological conditions included rosacea (1985), ak (2002), photoaging on face (2017), and seborrheic keratoses on bilateral upper and lower extremities. lsrs: d1 none; d8 flaking/scaling moderate, erythema moderate, crusting moderate, erosion/ulceration mild, swelling mild; d15 flaking/scaling mild, erythema mild, crusting mild; d29 and d57 none. b) the patient was a white (fitzpatrick ii), 69 year-old male. previous dermatological conditions included basal cell carcinoma back (2009), ak (2009), ak (2017), and basal cell carcinoma on the left cheek (2017). lsrs: d1 none; d8 flaking/scaling severe, erythema moderate, crusting moderate, swelling mild, erosion/ulceration mild; d15 flaking/scaling mild, erythema mild; d29 and d57 none. table 2. logistic regression model at day 57 (itt population) clearance factors p-value or estimate (95%ci) complete number of baseline ak lesions 0.0003 0.723 (0.608 – 0.861) treatment area location: face 0.0020 2.093 (1.310 – 3.347) partial age 0.0232 0.968 (0.940– 0.996) treatment area location: face 0.0030 2.099 (1.287– 3.422) ci, confidence interval; or, odds ratio; itt, intention to treat. • treatment-related aes were few and mostly mild transient application-site pruritus (tirbanibulin vs. vehicle: 9% vs. 6%) and pain (tirbanibulin vs. vehicle: 10% vs. 3%). no deaths, discontinuations, or serious aes related to tirbanibulin occurred. • lsr signs were present at baseline, increased after treatment, peaked on day 8 with tirbanibulin, decreased significantly by day 15, and mostly resolved by day 29. maximum mean ± standard deviation (sd) composite lsr scores were 4.1±2.32 and 1.0±1.14 for tirbanibulin and vehicle group, respectively. • lsrs were mostly transient mild or moderate erythema and flaking/scaling. severe lsrs were observed in less than 10% in each group. all lsrs resolved or returned to baseline and did not require intervention. • at day 57, cc rates were significantly higher with tirbanibulin vs. vehicle (49.3% vs. 8.6%, p<0.0001), as were pc rates (72.2% vs. 18.1%, p<0.0001). median percent reduction in ak lesion count at day 57 was greater with tirbanibulin vs. vehicle (87.5% vs. 20.0%). • at day 57, cc/pc/median percent reduction were significantly higher for tirbanibulin vs. vehicle in the face (55.9% vs. 9.6% / 77.7% vs. 20.5% / 100% vs. 25.0%, p<0.0001 for all) and the scalp (35.7% vs. 6.4% / 60.9% vs. 12.7% / 83.3% vs. 18.3%, p<0.0001 for all). • logistic regression showed 2.1-fold greater odds of either cc or pc at day 57 for face location vs. scalp. odds of cc at day 57 was 28% lower for every 1-lesion increase in number of baseline lesions (table 2). figure 1 illustrates the evolution of olsen 1-2 facial ak lesions in two patients who achieved cc with tirbanibulin. • there was no significant relationship between baseline variables such as previous ak treatment (table 3), as well as fitzpatrick skin type (table 4) or bmi (kg/m2) (table 5) and clearance rates at day 57. previous ak treatment complete clearance partial clearance yes (n=174) no (n=179) yes (n=255) no (n=98) no, n (%) 116 (52.02%) 107 (47.98%) 169 (75.78%) 54 (24.22%) yes, n (%) 58 (44.62%) 72 (55.38%) 86 (66.15%) 44 (33.85%) p-value chi-square 0.1797 0.0513 fitzpatrick skin type complete clearance partial clearance yes (n=174) no (n=179) yes (n=255) no (n=98) type i, n (%) 25 (51.02%) 24 (48.98%) 35 (71.43%) 14 (28.57%) type ii, n (%) 98 (49.00%) 102 (51.00%) 141 (70.50%) 59 (29.50%) type iii, n (%) 43 (48.86%) 45 (51.14%) 65 (73.86%) 23 (26.14%) type iv, n (%) 7 (46.67%) 8 (53.33%) 13 (86.67%) 2 (13.33%) type v, n (%) 0 (0.00%) 0 (0.00%) 0 (0.00%) 0 (0.00%) type vi, n (%) 1 (100.00%) 0 (0.00%) 1 (100.00%) 0 (0.00%) p-value fisher 0.9900 0.7209 bmi complete clearance partial clearance yes (n=174) no (n=179) yes (n=255) no (n=98) mean, sd (%) 29.02 (5.81) 28.62 (4.27) 28.96 (5.44) 28.44 (4.02) p-value t-test 0.4579 0.3312 table 3. clearance rates at day 57 by previous ak treatment (itt population) ak, actinic keratosis; itt, intention to treat. table 4. clearance rates at day 57 by fitzpatrick skin type (itt population) itt, intention to treat. table 5. bmi by clearance rates at day 57 (itt population) bmi, body mass index; itt, intention to treat; sd, standard deviation. synopsis • notalgia paresthetica (np) is a common sensory neuropathy of the back characterized by chronic pruritus1 • there are no approved therapies for np • difelikefalin (dfk) activates kappa-opioid receptors on peripheral sensory neurons and suppresses itch predominantly by a neuromodulatory effect – intravenous (iv) dfk is approved for the treatment of moderate-to-severe pruritus in adults with chronic kidney disease undergoing hemodialysis2-5 o iv dfk is not addictive and is not a controlled substance – oral dfk is being developed across numerous chronic pruritic conditions6 objective • here we report the results of the phase 2 study (komfort; nct04706975) evaluating oral dfk for the treatment of moderate-to-severe pruritus in subjects with np methods study design • komfort was conducted in adults with a clinically confirmed diagnosis of np • the study design is shown in figure 1 primary endpoint • the primary endpoint was the change from baseline in the weekly mean of the daily 24-hour worst itch-numeric rating scale (wi-nrs) at week 8 other endpoints  • ≥4-point improvement in wi-nrs  • complete response in wi-nrs – defined as wi-nrs score of 0 or 1 for at least 70% of the daily non-missing wi-nrs scores for the week • safety assessments figure 1. komfort: phase 2 study design 8 weeks treatmentrun-in 7 days end of treatment 1:1 randomizationscreen baseline mean wi-nrs ≥5 placebo bid 4-week active extension ongoing oral dfk 2 mg bid bid, twice daily. results • a total of 126 subjects were randomized (placebo, n=63; dfk, n=62) • baseline demographics and disease characteristics were similar between groups (table 1) – subjects were predominantly white and female, and the mean age was approximately 60 years in both treatment groups table 1. baseline demographics and disease characteristics characteristic placebo (n=63) dfk 2 mg (n=62) age, mean (sd), y 60.2 (11.8) 59.3 (12.4) female, n (%) 42 (66.7) 48 (77.4) race, n (%) white 56 (88.9) 49 (79.0) black 4 (6.3) 10 (16.1) other/not reported 3 (4.8) 3 (4.8) bmi, mean (sd), kg/m2 28.7 (5.2) 29.7 (5.8) duration of notalgia paresthetica, mean (sd), y 8.2 (7.4) 8.9 (10.4) wi-nrs score, mean (sd) 7.6 (1.4) 7.6 (1.4) moderate (≥5 – <7), n (%) 20 (31.7) 21 (33.9) severe (≥7), n (%) 43 (68.3) 41 (66.1) bmi, body mass index. efficacy • dfk resulted in a significant reduction from baseline in the weekly mean wi-nrs score at week 8 (primary efficacy outcome: dfk, 4.0; placebo, 2.4; p=0.001; figure 2) figure 2. primary endpoint: change from baseline in wi-nrs at week 8 -5 -4 -3 -2 -1 0 ** week ls m ea n c ha ng e fr om b as el in e (w i-n r s ) baseline 1 2 3 4 5 6 7 8 placebo (n=63) dfk 2 mg (n=62)*** *** *** ** *** *** ** p=0.001 at week 8 *p<0.05; **p<0.01; ***p<0.001 vs placebo. analysis conducted in itt population. ls means from mixed effects model with repeated measures with terms for treatment, week, treatment by week interaction, and baseline wi-nrs score. bars indicate standard error. missing data were imputed using multiple imputation under missing-at-random assumption. itt, intent to treat; ls, least squares. • reduction in itch intensity was observed with dfk at day 1 compared with placebo (figure 3) • a significantly greater proportion of subjects achieved a ≥4-point improvement in wi-nrs score at week 8 with dfk vs placebo (figure 4) • at week 8, a significantly greater proportion of subjects receiving dfk achieved a complete response (wi-nrs of 0 or 1 on at least 70% of the daily non-missing wi-nrs scores for the week) compared with placebo (figure 5) figure 3. change from baseline in daily wi-nrs during week 1 -5 -4 -2 -3 -1 0 1 day ls m ea n c ha ng e fr om b as el in e (w i-n r s ) baseline p=0.001 ** 1 2 3 4 5 6 7 placebo (n=63) dfk 2 mg (n=62) * ** * * on day 7 ** *p<0.05; **p<0.01; ***p<0.001 vs placebo. analysis conducted in itt population. ls means from mixed effects model with repeated measures with terms for treatment, day, treatment by day interaction, and baseline wi-nrs score. bars indicate standard error. missing data were imputed using multiple imputation under missing-at-random assumption. figure 4. achievement of ≥4-point improvement in wi-nrs 1 8 7 8 11 16 19 18 3 30 43 44 44 41 41 41 0 10 20 30 40 50 1 2 3 4 5 6 7 8 week placebo (n=63) dfk 2 mg (n=62) *** *** *** ** * ** ** s ub je ct s, % *p<0.05; **p<0.01; ***p<0.001. analysis conducted in itt population. estimated percentages from a logistic regression with terms for treatment and baseline wi-nrs score. subjects with missing weekly wi-nrs scores for a particular week due to early termination were categorized as non-responders. no adjustments for multiplicity were made for the secondary or exploratory outcomes. figure 5. achievement of complete responsea in wi-nrs 0 10 20 30 40 50 1 2 3 4 5 6 7 8 week placebo (n=63) dfk 2 mg (n=62) s ub je ct s, % * ** ** * * ** * ** * 1 2 3 3 3 7 5 12 0 0 18 21 22 19 20 22 *p<0.05; **p<0.01; ***p<0.001. analysis conducted in itt population. acomplete response was defined as wi-nrs score of 0 or 1 for at least 70% of the daily non-missing wi-nrs scores for the week. estimated percentages from a logistic regression with terms for treatment and baseline wi-nrs score. subjects with missing weekly wi-nrs scores for a particular week due to early termination were categorized as non-responders. no adjustments for multiplicity were made for the secondary or exploratory outcomes. a phase 2 study of oral difelikefalin for moderate-to-severe pruritus in subjects with notalgia paresthetica (komfort) brian s. kim, md, mtr1; robert bissonnette, md, frcpc2; kristine nograles, md3; catherine munera, phd3; nilam shah, pharmd3; alia jebara, md3; joshua cirulli, pharmd3; joana goncalves, md3; mark lebwohl, md1 1icahn school of medicine at mount sinai, new york, ny, usa; 2innovaderm research, montreal, qc, canada; 3cara therapeutics, stamford, ct, usa presented at: the fall clinical dermatology conference; october 20–23, 2022; las vegas, nv safety • all adverse events (aes) in dfk-treated subjects were mild to moderate in severity (table 2) • the most common treatment-emergent aes (teaes) leading to discontinuation were dizziness (n=5; 8.1%) and nausea (n=4; 6.5%) in the dfk group and abdominal pain (n=2, 3.2%) in the placebo group • headache, dizziness, constipation, and increased urine output were more commonly reported in subjects treated with dfk (table 3) table 2. summary of teaes subjects, n (%) placebo (n=63) dfk 2 mg (n=62) ≥1 teae 32 (50.8) 35 (56.5) ≥1 serious teae 0 0 teaes leading to discontinuation of trial regimen 4 (6.3) 12 (19.4) safety analyses were conducted in the safety population, which was defined as all randomized subjects who received ≥1 dose of study drug based on actual treatment received. table 3. most commonly reported teaes teaes (≥5% frequency), n (%) placebo (n=63) dfk 2 mg (n=62) nausea 7 (11.1) 8 (12.9) abdominal paina 8 (12.7) 7 (11.3) headache 3 (4.8) 7 (11.3) dizziness 2 (3.2) 7 (11.3) constipation 4 (6.3) 6 (9.7) increased urine outputb 1 (1.6) 5 (8.1) safety analyses were conducted in the safety population, which was defined as all randomized subjects who received ≥1 dose of study drug based on actual treatment received. aincludes the preferred terms abdominal pain, upper abdominal pain, abdominal discomfort, and lower abdominal pain. bincludes increased urine output and pollakiuria. conclusions • the phase 2 komfort study demonstrated that oral dfk significantly reduced itch intensity compared with placebo in subjects with np • the onset of action was evident at day 1 and maintained through week 8 • a significantly greater proportion of subjects receiving dfk vs placebo achieved a complete response • dfk was generally well tolerated • the most commonly reported aes were headache, transient dizziness, constipation, and increased urine output • the results of this phase 2 trial support the role of kappa-opioid receptor activation for the control of neuropathic itch • these findings underscore that dfk has the potential to fill a significant unmet need and warrants further clinical development in np references 1. ellis c. dermatol pract concept. 2013;3:3-6. 2. fishbane s, et al. n engl j med. 2020;382:222-232. 3. topf j, et al. kidney med. 2022;4(8):100512. 4. korsuva. package insert. cara therapeutics, inc.; 2021. 5. kapruvia. summary of product characteristics. vifor fresenius medical care renal pharma france; 2022. 6. kim bs, et al. oral difelikefalin reduces pruritus in atopic dermatitis. presented at: the 30th european academy of dermatology and venereology congress; september 29–october 2, 2021. acknowledgments this study was sponsored by cara therapeutics. the authors thank the study investigators and patients who participated in this study. we also gratefully acknowledge illyce nunez, phd, and callie grimes, phd (peloton advantage, llc, an open health company, parsippany, nj), for medical writing and editorial support, which was funded by cara therapeutics, under the direction of the authors. correspondence mark lebwohl – lebwohl@aol.com disclosures bsk: abbvie, abrax japan, astrazeneca, boehringer ingelheim, bristol myers squibb, cara therapeutics, escient pharmaceuticals, galderma, glaxosmithkline, granular therapeutics, incyte, leo pharma, lilly, pfizer, recens medical, regeneron, sanofi, trevi therapeutics – consulting. cara therapeutics and leo pharma – research grant. rb: abbvie, arcutis, arena pharma, asana biosciences, bellus health, bluefin biomedicine, biomimetix, boehringer ingelheim, boston, brickell, cara therapeutics, clexio, dermavant, eli lilly, emd serono, evidera, galderma, glaxosmithkline, incyte, inmagene bio, janssen, kiniksa, kyowa kirin, leo pharma, novan, novartis, pfizer, ralexar, rapt therapeutic, regeneron, respivant, sanofi, sienna, target rwe, and vyne therapeutics – advisor, consultant, speaker, investigator, and/or research grant. innovaderm research – employee and shareholder. kn, cm, ns, aj, jc, & jg: cara therapeutics, inc. – employment. ml: mount sinai – employee. abbvie, amgen, arcutis, avotres, boehringer ingelheim, cara therapeutics, dermavant sciences, eli lilly, incyte, janssen research & development, llc, ortho dermatologics, regeneron, and ucb – research funds. aditum bio, almirall, altrubio inc., anaptysbio, arcutis, inc., aristea therapeutics, arrive technologies, avotres therapeutics, biomx, boehringer ingelheim, bristol myers squibb, cara therapeutics, castle biosciences, corrona, dermavant sciences, dr. reddy’s laboratories, evelo biosciences, evommune, inc., facilitation of international dermatology education, forte biosciences, foundation for research and education in dermatology, helsinn therapeutics, hexima ltd., leo pharma, meiji seika pharma, mindera, pfizer, seanergy, and verrica – consultant. powerpoint presentation comparing electrical impedance spectroscopy to traditional clinical adjunctive tools in the detection of melanoma ryan m. svoboda, md ms1, abigail i. franco, md2, darrell s. rigel, md ms3* background objectives methods results limitations conclusions 1national society for cutaneous medicine, new york, ny 2st. joseph’s hospital, syracuse, ny 3ronald o. perelman dept. of dermatology, nyu medical center, new york, ny • early detection of melanoma leads to improved outcomes • despite adjuncts such as dermoscopy, clinical detection remains challenging • electrical impedance spectroscopy (eis) (nevisense, scibase ab, stockholm, sweden) has been shown to have potential as a diagnostic aid for the detection of melanoma • to compare the results of eis to clinical detection algorithms in biopsy-proven melanoma lesions • to determine the correlation between eis score and pathologic staging • only biopsy-positive lesions were included in the data analysis • there were few advanced lesions • eis potentially has a lower incidence of false negative results than other common diagnostic adjuncts in the detection of melanoma • there appears to be a moderate positive correlation between increasing eis score and advancing tumor stage • a subset of 265 lesions from the eis pivotal trial (2,416 total lesions from 22 sites in 7 countries) was analyzed, representing all biopsy-proven melanoma specimens in the sample • prior to biopsy, each lesion was characterized by: • clinical abcd rule • abcd rule of dermoscopy (cutoff >4.75 for +ve score) • 7-point checklist (cutoff ≥3 for +ve score) • weighted 7-point checklist (cutoff ≥3 for +ve score) • eis (cutoff ≥4 for +ve score) *disclosures: the data for this study was supplied by scibase, ab. no compensation was received by the authors. tumor stage number of lesions percentage of sample in situ 112 42.3% t1a 94 35.5% t1b 19 7.2% t2a 24 9.1% t2b 11 4.2% t3a 1 0.4% t3b 3 1.1% t4a 1 0.4% distribution of tumor stage in a sample of 265 biopsy-proven melanoma lesions technique percentage of false negative cases sensitivity for detection of melanoma p-value* electrical impedance spectroscopy 3.4% 96.6% clinical abcd rule 12.8% 87.2% 0.294 abcd dermoscopy rule 45.8% 54.2% 0.003 seven-point checklist 50.8% 49.2% 0.008 weighted seven-point checklist 39.3% 60.7% 0.001 sensitivity of clinical tools for the detection of melanoma in a sample of 265 biopsy-proven melanoma lesions correlation between pathologic staging and eis score *comparing sensitivity to that of eis background ■ biologic therapies are commonly used in the us to treat moderate to severe plaque psoriasis, a chronic, relapsing inflammatory immune-mediated skin disease that has been shown to have a negative impact on patients’ productivity and quality of life as well as increased medical care costs.1-3 ■ guselkumab is a subcutaneously administered anti-interleukin (il)-23 monoclonal antibody that is approved in the united states (us) for the treatment of moderate to severe plaque psoriasis and has been shown in 2 head-to-head phase 3 clinical trial to be superior to subcutaneously administered adalimumab, an anti-tnf alpha treatment. ■ insurers are seeking comparative effectiveness and cost data for these patients to inform formulary and benefit design decisions. objectives ■ to estimate the cost per responder in the us for guselkumab relative to adalimumab in the first year of treatment based on efficacy results from a head to head clinical trial, voyage 14 methods ■ the calculation used to estimate the cost per responder was: cost per responder = (per unit drug costs) x (# of doses per 52 weeks) percent of patients with a response at 48 weeks (voyage 1) ■ dosing was based on the fda label in the first year, and number of doses was based on a full 52-week year for both products as shown in table 1: table 1. dosing and pricing inputs for guselkumab and adalimumab cost comparison methodology1,2 biologic dosing pricing3 number of doses 52 weeks guselkumab 100 mg administered by subcutaneous injection at week 0, week 4 and every 8 weeks thereafter wac per 100 mg: $9,684.00 8 (100 mg) adalimumab 80 mg initial dose (2 x 40 mg), followed by 40 mg every other week starting one week after initial dose wac per 40 mg: $2,220.62 28 (40 mg) 1the wholesale acquisition cost (wac) is a published list price. wac does not contain any discounts, price concessions or charge backs extended to wholesalers or other end users. wac is not intended to represent an actual sales price to customers. wholesalers and distributors determine the actual sales price to end-user customers. 2wholesale acquisition cost (wac) as of august 2017. ■ efficacy (or response) was based on the percentage of patients reaching at least a 75% improvement in the psoriasis area and severity index (pasi75) or at least a 90% improvement in pasi (pasi 90) or 100% improvement in pasi (pasi 100) response at 48 weeks in the voyage 1 head-to-head trial for guselkumab and adalimumab. ■ the 48-week efficacy results were extrapolated to 52 weeks (assumed unchanged) for the first-year cost-per-responder calculation. results ■ the first-year costs were $77,472 (8 x $9,684.00) for guselkumab and $62,177 (28 x $2,220.62) for adalimumab. ■ figure 1 shows the percentage of patients in the voyage 1 trial reaching a pasi 90 response at 48 weeks. figure 1. percent of patients reaching each pasi response at 48 weeks 0 20 40 60 80 10 30 50 70 90 100 p er ce n ta g e o f p at ie n ts pasi 75 87.8% 62.6% 76.3% 47.9% 47.4% 23.4% pasi 90 guselkumab adalimumab pasi 100 ■ figure 2 shows the cost per responder estimates for guselkumab and adalimumab for the voyage 1 primary endpoint, a response of pasi 90. figure 2. cost per responder for pasi 90 responders induction year $101,536.04 $129,806.60 $0.00 $20,000.00 $40,000.00 $60,000.00 $80,000.00 $100,000.00 $120,000.00 $140,000.00 pasi 90 w k 5 2 c o st p er r es p o n d er induction year guselkumab vs. adalimumab cost per responder pasi 90 (voyage 1, voyage 1) guselkumab adalimumab ■ figure 3 shows the cost per responder estimates for the three different pasi response rates, pasi 75, pasi 90 and pasi 100. for all three response rates, the cost per responder was lower for guselkumab than for adalimumab. figure 3. induction year cost per responder for all three pasi response levels $0 $100,000 $125,000 $175,000 $225,000 $275,000 $200,000 $50,000 $25,000 $75,000 $150,000 $250,000 $300,000 c o st p er r es p o n d er pasi 75 $88,237 $99,325 $101,536 $129,807 $163,443 $265,715 pasi 90 guselkumab adalimumab pasi 100 conclusions ■ this cost per responder analysis from the voyage 1 trial demonstrates that guselkumab is a more cost-effective treatment with a lower cost per responder than adalimumab for achieving a pasi 90, pasi 75, and a pasi 100 response in the first year of treatment among patients with moderate to severe plaque psoriasis. references 1. vanderpuye-orgle, zhao y, lu j, shrestha a, sexton a, seabury s, lebwohl m. evaluating the burden of psoriasis in the united states. j am acad dermatol. 2015; 72: 961-7. 2. brezinski ea, dhillon js, armstrong aw. economic burden of psoriasis in the united states: a systematic review. jama dermatol. 2015; 151: 651-8. 3. jacobs p, bissonnette r, guenther lc. socioeconomic burden of immune-mediated inflammatory diseases – focusing on work productivity and disability. j rheumatol suppl. 2011. 88: 55-61. 4. blauvet a, papp ka, griffiths cem, randazzo b, wasfi y, shen y-k, li s, kimball ab. efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the continuous treatment of patients with moderate to severe psoriasis: results from the phase iii, double-blinded, placebo and active comparator-controlled voyage 1 trial. j am acad dermatol. 2017. 76: 405-417. contact information amanda teeple, mph manager, dermatology, immunology health economics and outcomes research janssen scientific affairs, llc, horsham, pa email: ateeple@its.jnj.com this analysis was supported by janssen scientific affairs, llc. poster presented at the fall clinical dermatology conference, october 12–15, 2017, las vegas, nv, usa. an electronic version of the poster can be viewed by scanning the qr code. the qr code is intended to provide scientific information for individual reference. the pdf should not be altered or reproduced in any way. cost per responder analysis of guselkumab versus adalimumab using efficacy results from a head-to-head clinical trial in patients with moderate to severe plaque psoriasis a. teeple, mph; e. muser, pharmd, mph janssen scientific affairs, llc., horsham, pa fc17posterjanssenteeplecostperresponder.pdf skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 269 skimages pustular penile pyoderma gangrenosum: a puzzling clinical presentation mezni line, md1, elhadadi farah, md1, ismaili nadia md,phd1 1ibn sina university hospital dermatology department, mohammed v university, rabat, morocco figure 1 : penile pyoderma gangrenosum : erosive, and sharply demarcated lesions on the glans penis pyoderma gangrenosum (pg) is a recurrent, chronic inflammatory neutrophilic dermatosis. it is usually associated with an underlying systemic disease such as inflammatory bowel disease and hematological malignancy. pg may occur skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 270 figure 2: biopsy of the glans showing an ulcerated epidermis ,fibrinous exudate, neovascularization, and an acute inflammation beneath characterized by a dense and diffuse, predominantly neutrophilic infiltrate ( h&e x100) anywhere on the body while it is classically described on the lower extremities1. a healthy 60-year-old moroccan man developed a persistent, erythematous vesiculo-pustular erosive, and sharply demarcated lesions on the glans penis (figure 1). the patient denied extramarital sex and no relevant medical history has been reported. further physical examinations were unremarkable. the lesions were unresponsive to topical fusidic acid 2% cream twice daily for a period of 2 weeks. the skin biopsy showed patterns of pg (figure 2) and tissue cultures were negative for bacteria, mycobacteria, and fungus infection, full blood screening was normal. topical clobetasol propionate 0.05% was prescribed once daily for 4 weeks and every other day for 4 weeks resulting in a complete resolution. the follow-up period was marked by a recurrence after 8 months, lesions were treated with topical tacrolimus 0.1% once daily for 1-month and completely healed after 2 weeks. four clinical variants of pyoderma gangrenosum have been described: ulcerative, bullous, vegetative, and pustular. frequently, one form of pg is seen in a patient and up to 25% of patients recall a history of pathergy phenomenon (the abnormal development of skin lesions at the sites of trauma, including minor injuries)1. the pustular form is a rare variant showing painful vesiculo-pustular lesions that don’t ulcerate and are commonly observed on the trunk and on the extensor surfaces. histopathology shows a dermal neutrophilic infiltrate and subcorneal neutrophilic micro pustules. it is commonly observed in patients with active ulcerative colitis. only a few cases have been reported in the literature and were associated with hyperglycemia and https://www.ncbi.nlm.nih.gov/pmc/articles/pmc4553856/#ref1 skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 271 hyperlipidemia. the diagnosis might be challenging as there are no specific histopathologic or immunofluorescent features and it is mainly based on clinical hallmarks, the association with systemic diseases and the exclusion of differential diagnosis. topical tacrolimus therapy is effective and is recommended as a first-line modality2. surgical debridement is not recommended in the acute stage due to the risk of tissue progression3. hence, we report the first case of pustular penile pyoderma gangrenosum without an underlying disease successfully treated by topical monotherapy. conflict of interest disclosures: none funding: none corresponding author: mezni line, md av lamfadel cherkaoui 10100 rabat, morocco phone : (+212) 642-657-940 e-mail : mezni_line@outlook.com references: 1. shankar s, et al. pustular pyoderma gangrenosum. clin exp dermatol 2003; 28:600 2. larsen cg, thyssen jp. pustular penile pyoderma gangrenosum successfully treated with topical tacrolimus ointment. acta derm venereol 2012;92:104-5. 3. chia mw, et al. pustular pyoderma gangrenosum: an uncommon variant which is easily misdiagnosed. dermatol online j 2008 14: 21 skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 497 research letter severity of covid-19 in patients with dermatomyositis: a single center, retrospective observational cohort study jessica johnson, bs1, amy s. nowacki, phd2, jatin narang, md1, sarah young, md3, anthony p. fernandez, md3,4 1 cleveland clinic lerner college of medicine, case western university, cleveland, oh 2 quantitative health science, cleveland clinic, cleveland, oh 3 department of dermatology, cleveland clinic, cleveland, oh 4 department of pathology, cleveland clinic, cleveland, oh patients with chronic immune-mediated diseases (imids), especially when taking certain immunomodulatory medications, have been shown to have an increased risk of developing severe covid-19.1-3 although dermatomyositis (dm) patients have been included in large cohorts of patients with imids evaluating for covid-19 risk and severity, there is little literature specifically evaluating dm patient cohorts. we performed a single-center, retrospective cohort study to evaluate the severity of covid-19 in dm patients and to assess for risk factors related to severe covid-19 disease course. only patients >18 years-old with confirmed, positive covid-19 polymerase-chain reaction (pcr) tests between march 2020 – july 2021 were included. all patients met european league against rheumatism (eular) criteria for dm diagnosis. 4 patients must have been seen by a cleveland clinic provider for their dm within the last 10 years (january 2011 – july 2021). hospitalization was defined as >1 night in the hospital for covid-19. depending on the sample size, the wilcoxon rank sum test or fisher’s exact test was used to compare the characteristics of the hospitalized versus not hospitalized patients in the dm cohort. our cohort included 27 patients with confirmed dm. detailed characteristics of our dm cohort are included in table 1. within our cohort, 74.1% were on systemic therapy for their dm at the time of their covid-19 diagnosis (table 2). within the dm cohort, 6 (22.2%) were hospitalized for their covid-19 disease. one individual required icu care (3.7%), and another died as a result of covid-19 (3.7%). despite an underlying increased risk for thromboembolic events, none of the patients in our dm cohort had a thrombotic event during their covid-19 infection 5. additionally, only one of the patients in our cohort had a worsening of their dm symptoms after their covid-19 infection. the hospitalized dm patients had a median age of 66 years, compared to 52 years in the non-hospitalized group (table 2). no clinical features significantly differed between the hospitalized and non-hospitalized dm introduction other results skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 498 table 1. dermatomyositis cohort demographic factors count 27 female 24 (88%) age* 54 (26, 67) bmi* 27.2 (22.7, 32.1) dm subtypes classic 20 (74%) amyopathic 1 (4%) juvenile 3 (11%) malignancy associated 3 (11%) medications at time of covid-19 diagnosis corticosteroids 6 (22%) dmards 18 (67%) combined systemic therapy (corticosteroids + dmard or >1 dmard) 10 (37%) any systemic therapy 20 (74%) dm autoantibody status positive myositis antibodies 12 (44%) negative myositis antibodies 9 (33%) n/a 6 (22%) *median (q1 – q3) skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 499 table 2. hospitalized versus non-hospitalized dermatomyositis patients hospitalized (n = 6) not hospitalized (n = 21) p-value female 6 (100%) 18 (86%) .99 age* 56 (40 – 69) 54 (25 – 67) .58 bmi* 31.9 (27.9, 36.4) 26.5 (22.5, 30.9) .10 dm subtypes classic 5 (83%) 15 (71%) amyopathic 0 1 (5%) juvenile 0 3 (14%) malignancy associated 1 (17%) 2 (10%) medications at time of covid19 diagnosis corticosteroids 3 (50%) 3 (14%) .10 dmards 5 (83%) 13 (62%) .63 combined systemic therapy (corticosteroids + dmard or >1 dmard) 3 (50%) 7 (33%) .56 any systemic therapy 6 (100%) 14 (67%) .15 dm autoantibody status positive myositis antibodies 3 (50%) 9 (43%) negative myositis antibodies 2 (33%) 7 (33%) n/a 1 (17%) 5 (24%) *median (q1 – q3) skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 500 patients in our cohort. however, corticosteroid usage was higher in the hospitalized group, with 50% on corticosteroids when infected with covid-19 compared to 14.3% in the non-hospitalized group. additionally, body mass index (bmi) was higher in hospitalized patients compared to non-hospitalized patients (31.9 kg/m2 vs 26.5 kg/m2). of those on corticosteroids when hospitalized, 2 were on dosages > 10 mg. dmard use and combined corticosteroid and dmard use were both slightly higher in the hospitalized group (83.3% vs. 62%, 50% vs. 33%, respectively). similarly, 100% of dm patients who were hospitalized were on some form of systemic therapy, compared to 67% in the nonhospitalized group. in summary, our results suggest risk factors for severe covid-19 in dm patients include those previously identified in other cohorts of autoimmune disease patients; namely, advanced age, higher body mass index (bmi) and active treatment with immunosuppressive agents.1,4 the main limitation of our study is its small sample size, which limited our ability to potentially detect significant differences between clinical characteristics of hospitalized vs. nonhospitalized dm patients. therefore, we focused on descriptive measures and the clinical importance of observed differences to generate hypotheses in the dm cohort. alternatively, strengths of our study include an ability to review detailed information about our cohort patients, thus being confident about their dm diagnosis, medication regiment at time of covid-19 diagnosis, and their covid-19 disease course. further characterization in larger cohorts should be conducted to explore these possible associations. until then, awareness of these potential risks is important for clinicians caring for dm patients in order to optimize their care and protection from a severe covid-19 disease course. conflict of interest disclosures: jj, an, jc, sy and have no conflicts of interest or financial disclosures. apf is an investigator for pfizer, corbus, mallinckrodt, and novartis and receives personal research support from mallinckrodt and novartis; honorarium from abbvie, alexion, bms, ucb, novartis, and mallinckrodt for consulting and advisory board participation, and honorarium from abbvie, novartis, kyowa kirin and mallinckrodt for teaching and speaking (non-promotional). funding: none corresponding author: anthony p. fernandez, md, phd departments of dermatology and pathology cleveland clinic; 9500 euclid avenue, a61 cleveland, oh 44195 telephone: (216) 445-8776 fax: (216) 636-0711 email address: fernana6@ccf.org references: 1. gianfrancesco m, hyrich kl, hyrich kl, et al. characteristics associated with hospitalisation for covid-19 in people with rheumatic disease: data from the covid-19 global rheumatology alliance physicianreported registry. ann rheum dis. 2020;79(7):859-866. doi:10.1136/annrheumdis-2020-217871 2. strangfeld a, schäfer m, gianfrancesco ma, et al. factors associated with covid-19related death in people with rheumatic diseases: results from the covid-19 global rheumatology alliance physician-reported registry. ann rheum dis. 2021;80(7):930. doi:10.1136/annrheumdis-2020-219498 3. severity of covid-19 and survival in patients with rheumatic and inflammatory diseases: data from the french rmd covid-19 cohort of 694 patients. ann rheum dis. 2020;80(4):527-538. doi:10.1136/annrheumdis-2020-218310 4. lundberg ie, tjärnlund a, bottai m, et al. 2017 european league against rheumatism/american college of rheumatology classification criteria for adult and juvenile idiopathic inflammatory conclusion mailto:fernana6@ccf.org skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 501 myopathies and their major subgroups. ann rheum dis. 2017;76(12):1955-1964. doi:10.1136/annrheumdis-2017-211468 5. li y, wang p, li l, wang f, liu y. increased risk of venous thromboembolism associated with polymyositis and dermatomyositis: a meta-analysis. ther clin risk manag. 2018;14:157. doi:10.2147/tcrm.s157085 acknowledgements: medical writing support was provided by prescott medical communications group (chicago, il) with financial support from ortho dermatologics; ortho dermatologics is a division of bausch health us, llc • presented at the fall clinical dermatology conference for pas and nps • june 3-5, 2022 • scottsdale, az synopsis � vehicle design and optimization of topical formulations are critical to the drugdevelopment process, as product vehicle and active/inactive ingredients can contribute to drug tolerability/efficacy and patient preference/adherence1,2 � retinoids are a mainstay of acne treatment, though topical retinoids—such as tretinoin—can be associated with significant cutaneous irritation and drying, which can lead to poor adherence3,4 � to mitigate these issues, tretinoin 0.05% lotion (altreno®) was formulated using a polymeric honeycomb matrix, which allows for efficient and uniform delivery of micronized tretinoin and moisturizing/hydrating ingredients5,6 (figure 1) � branded topical acne therapies, however, are often substituted at the pharmacy for a generic version, without accounting for the physiochemical differences between formulations and the potential impact of this product substitution figure 1. polymeric emulsion technology for tretinoin 0.05% lotion polymeric matrix traps micronized tretinoin particles micronized tretinoin [kircik et al. 2019]6. cryo scanning electron microscopy imaging of the polymeric matrix (×1000). micronized tretinoin particles are predominantly <10 microns in diameter. objective � to compare the tolerability and participant preference of two tretinoin formulations: a branded 0.05% lotion (altreno) and a frequently dispensed 0.05% generic cream (taro) methods � in this single-center, double-blinded, split-face study, females with acne aged ≥18 years were randomized to apply tretinoin lotion or generic cream once daily to the right or left cheek for 2 weeks • first application occurred at the research site under the supervision of a research coordinator � assessments were conducted immediately after first use and after two weeks of split-face drug application � the investigator assessed erythema, scaling, skin dryness, softness, smoothness, radiance, and brightness on a 5-point scale (0=none, 1=minimal, 2=mild, 3=moderate, 4=severe) � participants completed a 16-item facial marketing questionnaire assessing their impressions of the products and their skin on a 9-point scale (1=agree completely, 9=disagree completely) for each side of their face participant assessments � after 2 weeks of use, average impression rating scores on each of the 16 questionnaire items were better (lower) for lotion versus cream (p<0.05 on 15 of 16 items; figures 3 and 4) • similar results were observed immediately after one use (p<0.05 on 10 of 16 items; data not shown) � more than 70% of participants agreed (rating score 1–3) that the tretinoin lotion was gentle, comfortable/soothing, spreadable, absorbent, not sticky, and left a minimal white residue versus <40% for generic cream (figure 3) � agreement scores on skin sensation (feels soft, smooth, comforted/soothed/calm, not dry and looks smoother, less dull, less flaky) were similarly higher for lotion versus cream (>60% vs ≤40%; figure 4) � overall, approximately 70% of participants preferred to take tretinoin lotion home over cream both after first use and 2 weeks of use (figure 5) figure 3. self-assessments of produc t properties at week 2 (n=25) feels gentle feels comfortable/soothing relieves tightening sensation spreads well absorbs well is not sticky leaves minimal white residue has a neutral smell overall satisfaction with product 1 2 3 4 5 6 7 8 9 questionnaire scale 2.52 *** 5.12 2.64 ** 4.72 3.16 ** 5.60 1.64 *** 7.32 2.12 *** 6.40 3.52 * 6.08 1.92 *** 7.28 2.48 4.16 3.08 *** 5.72 84 80 64 92 88 72 92 84 68 lotion 32 36 24 8 20 28 12 52 32 generic % agreea more agreement more disagreementtretinoin lotion generic cream *p<0.05, **p<0.01, ***p<0.001 vs generic cream. questions rated on a scale of 1=agree completely to 9=disagree completely. adefined as a rating of 1, 2, or 3 on the questionnaire scale. figure 4. self-assessments of skin properties at week 2 (n=25) feels soft feels smooth feels comforted/soothed/calmed does not feel dry looks smoother looks less dull looks less �aky 1 2 3 4 5 6 7 8 9 questionnaire scale 2.64 ** 5.04 2.60 ** 4.84 3.28 * 5.52 3.40 ** 5.80 3.20 ** 5.60 3.16 ** 5.52 3.60 ** 6.48 80 80 72 68 76 72 64 lotion 32 40 24 28 28 28 20 generic % agreea more agreement more disagreementtretinoin lotion generic cream *p<0.05, **p≤0.01, ***p<0.001 vs generic cream. questions rated on a scale of 1=agree completely to 9=disagree completely. adefined as a rating of 1, 2, or 3 on the questionnaire scale. vehicle formulation impacts tolerability and patient preference: comparison of tretinoin branded lotion and generic cream zoe d draelos, md1; amber blair, pa-c2; emil a tanghetti, md3 1dermatology consulting services, pllc, high point, nc; 2dermatology, laser & vein specialists of the carolinas, charlotte, nc; 3center for dermatology and laser surgery, sacramento, ca results participants � twenty-five female participants with a mean age of 40.6 years (range: 19–69 years) enrolled in and completed the study � all participants had a fitzpatrick skin type of 1 or 2 and self-identified as white � almost half of participants had combination skin type (48%), followed by dry (32%), normal (12%), and oily (8%) investigator assessments � after first use, investigator assessments were not significantly different between the lotionand cream-treated sides of the face, and there was no/minimal erythema, scaling, or dryness with either treatment (figure 2; open bars) � at week 2, the cream-treated side of the face had significantly more erythema (144%), scaling (144%), and dryness (122%) versus the lotion-treated side (p<0.01 each; figure 2; filled bars) � the lotion-treated side also demonstrated significantly enhanced softness, smoothness, radiance, and brightness (~40% difference, p<0.01, each) versus cream at week 2 (figure 2; filled bars) figure 2. investigator assessments of irritation and skin appearance (n=25) 0.5 1 1.5 3.5 0 2 2.5 3 erythema m e a n v a lu e s 4 generic cream: first use tretinoin lotion: first use generic cream: week 2 tretinoin lotion: week 2 scaling dryness lack of softness lack of smoothness lack of radiance lack of brightness minimal none mild moderate severe m o re f av o ra b le **p<0.01 vs generic cream at week 2. figure 5. self-assessment of produc t preference 68% 32% 72% 28% overall, which product would you like to take home? after �rst use after 2 weeks tretinoin lotion generic cream conclusions � in this split-face study, tretinoin 0.05% lotion led to significantly less investigator-assessed erythema, scaling, and dryness versus generic cream after 2 weeks of once-daily use, accompanied by a significant improvement in skin appearance (softness, smoothness, radiance, and brightness) � participants also significantly preferred properties of the lotion formulation (eg, gentle, spreadable, absorbs well) and skin sensation (eg, soft, soothed, not dry, less dull) with lotion versus cream � these results demonstrate the importance of a well-designed topical formulation—such as tretinoin 0.05% lotion—on both improved tolerability and patient preference, underscoring the potential negative impact of generic switching at the pharmacy • given the established impact of tolerability and patient preference on drug adherence and treatment success,2,7 this further underscores the potential negative effect of generic switching at the pharmacy references 1. piacquadio d, and kligman a. j am acad dermatol. 1998;39(2 pt 3): s67-73. 2. eastman wj, et al. cutis. 2014;94(1):46-53. 3. zaenglein al, et al. j am acad dermatol. 2016;74(5):945-73.e33. 4. sevimli dikicier b. j int med res. 2019;47(7):2987-2992. 5. tyring sk, et al. j drugs dermatol. 2018;17(10):1084-1091. 6. kircik lh, draelos zd, and berson ds. j drugs dermatol. 2019;18(4):s148-154. 7. dreno b, et al. int j dermatol. 2010;49(4):448-56. author disclosures zoe d draelos received funding from ortho dermatologics to conduct the research presented in this poster. amber blair is director at large for the sdpa board of directors. emil a tanghetti has served as speaker for novartis, ortho dermatologics, sun pharma, lilly, galderma, abbvie, and dermira; served as a consultant/ clinical studies for hologic, ortho dermatologics, and galderma; and is a stockholder for accure. skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 424 brief article successful treatment of cutaneous collagenous vasculopathy with pulsed dye laser: a case report emily l. ahearn, bs1, lihi tzur, md2, meera mahalingam, md, phd3, nellie konnikov, md, faad4 1 tufts university school of medicine, boston, ma 2 department of dermatology, tufts medical center, boston, ma 3 dermatopathology section, department of pathology and laboratory medicine, va integrated service network (visn-1), west roxbury, ma 4 dermatology section, department of medicine, va integrated service network (visn-1), jamaica plain, ma and west roxbury, ma cutaneous collagenous vasculopathy (ccv) is a relatively rare microangiopathy that presents clinically as symmetrically distributed, blanching telangiectasias that progressively spread over several years.1 these generally asymptomatic vascular lesions first appear on the lower limbs before spreading to the trunk and arms, sparing the nails, mucosa, and without evidence of systemic involvement. given that the clinical presentation of ccv can be indistinguishable from other vascular disorders with cutaneous telangiectasias, especially generalized essential telangiectasia (get), diagnosis requires biopsy to confirm the histopathology.2-3 distinctive histopathological findings of ccv include ectatic superficial blood vessels with thickened vessel walls containing type iv collagen, that stains periodic acid-schiff (pas) positive.1-2 fewer than fifty cases of ccv have been reported in the literature since it was first described by salama and rosenthal in abstract cutaneous collagenous vasculopathy (ccv) is clinically characterized by symmetrical, progressive telangiectasias and an absence of systemic involvement. histopathology is distinct and helps in differentiation from other vascular conditions that result in cutaneous telangiectasias. we present a case of biopsy proven ccv that had localized clearance following biopsy and was successfully treated with pulsed dye laser. a healthy 36-year-old male presented with a 10-year history of progressive, blanching telangiectasias of the legs, thighs, and forearms. a punch biopsy of a representative patch on the patient’s right thigh demonstrated telangiectasias with thickened paspositive vessel walls and a sparse perivascular lymphoid infiltrate, features consistent with a diagnosis of ccv. while there was localized clearance at the biopsy site and adjacent skin, the patient opted for treatment with pdl for his lesions elsewhere. after testing various pdl settings, greatest cosmetic improvement and minimal pih was achieved with a spot size of 7 mm, pulse duration of 3 milliseconds (ms) and a fluence of 8 j/cm2. continued resolution of ccv was noted at 24 months. we present this case to underscore the potential efficacy of pdl in the treatment of ccv. introduction skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 425 2000, and the etiology of these telangiectatic lesions is not well understood.1 one study published by salama et al. suggested that damage to endothelial walls results in intravascular fibrin thrombi, which may induce perivascular fibrosis via disordered collagen production by veil cells.4 numerous cases have identified common comorbidities in patients with ccv, which include hypertension, diabetes, and dyslipidemia.5 while microvasculature changes can be observed in cardiovascular conditions, it is unclear whether or how these comorbidities are involved in the pathophysiology of ccv. regarding the treatment of ccv, four cases have reported improved cosmetic appearance and/or lack of progression of ccv following pulsed dye laser (pdl) therapy, and two additional publications have demonstrated success with other lightbased therapies.6-10 our case highlights a sustained response with 2 years of follow up as well as ideal pdl settings in a patient with fitzpatrick skin type i-ii. additionally, as there are so few published cases in the literature regarding ccv as an entity, we hope to further its recognition in the dermatologic community. we report a 36-year-old male patient with no relevant past medical history who has developed ccv over a 10-year period, which is successfully being treated with pdl. notably, this patient experienced local clearance of ccv following biopsy, which to our knowledge has not been described in the literature. telangiectatic lesions elsewhere have responded well to pdl treatment. a 36-year-old healthy male with a 10-year history of telangiectasias on his bilateral upper and lower extremities initially presented to the dermatology clinic in 2018. he denied any history of easy bleeding or similar findings in family members and denied taking any medications. the telangiectasias began on his lower legs and spread to the thighs and forearms. examination revealed blanching telangiectasias coalescing into large patches covering his lower legs, onto the thighs and bilateral forearms (fig. 1a). there was no facial, nail, or mucosal involvement. biopsy of a representative area on his right thigh was performed, revealing telangiectasias with thickened vessel walls confirmed by pas and a sparse perivascular lymphoid infiltrate, consistent with ccv (fig. 2). the biopsy site healed well, remarkably leading to clearance of telangiectasias at biopsy site and adjacent surrounding skin (fig. 1b). figure 1a. bilateral upper thighs at presentation of ccv, showing diffuse, blanching telangiectasias. figure 1b. right thigh with local clearance of telangiectasias at biopsy site. case report skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 426 the patient began treatment with pulsed-dye laser (595 nm) and thus far has completed nine total treatments—eight treatments which included the thighs and two treatments involving the shins. various settings were tested to determine the best outcome with least amount of side effects. initially, a 7 mm spot size with 1.5 ms pulse duration at 7 j/cm2 was tested on the right thigh versus a 3 ms pulse duration with same spot size and energy on the left thigh. the patient noted more improvement with the 1.5 ms, but also more bruising and change in skin texture. at his third treatment, the pulse duration was increased to 6 ms due to patient endorsement of postinflammatory hyperpigmentation (pih) with the 3 ms pulse duration. given that there was less improvement using the 6ms pulse duration and near resolution of pih, the patient ultimately preferred to resume the 3 ms pulse duration at 8 j/cm2 for subsequent treatments. significant improvement is noted on the bilateral thighs as well as some improvement with pih on the shins (fig. 3a & 3b). the plan is to resume treatments to the shins post summer months and continue treatments on the thighs as needed. figure 2. histopathology of biopsy site demonstrating the telangiectasias with thickened vessel walls that are positive for pas. figure 3. bilateral thighs with improvement of telangiectasias after 8 treatments with pdl. skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 427 laser therapy is well documented to treat various cutaneous vascular lesions. given the rare and potentially underdiagnosed nature of ccv, its treatment has not been extensively reported; however, several cases have demonstrated success with pdl, intense pulsed light (ipl), and other variations of energy-based treatments.6-10 in our case, the patient had optimal improvement and minimal post-inflammatory hyperpigmentation with pdl at a wavelength of 595 nm, spot size of 7 mm, pulse duration of 3 ms and fluence of 8 j/cm2 for the treatment of his thighs and shins. previous pdl settings to treat ccv that have been reported include a wavelength of 585 nm, spot size of 7 mm, pulse duration of 2 ms and fluence of 8 j/cm2 for treatment of the legs.6 similar settings resulted in significant improvement of ccv in our patient with sustainable resolution with 24 months of follow up. however, the use of pdl for other conditions and varying skin types should take into consideration the propensity for pih when identifying treatment settings. in addition to improvement following pdl therapy, localized clearance of ccv status post biopsy was observed. although the underlying mechanism that would explain this localized clearance is unknown, it may be comparable to a reverse koebner reaction, which can be described as local trauma resulting in the resolution of a dermatosis. reverse koebner phenomenon has been reported in the setting of psoriasis, vitiligo, granuloma annulare, and small vessel vasculitis, among other dermatologic conditions.11-12 while many factors may influence the clearance of telangiectasias following biopsy, this is a unique aspect of this ccv case that has not been previously described. in summary, our case reiterates previously observed improvement in ccv patients with pdl laser. future studies may explore the pathophysiology and specific factors that induce ccv and whether a reverse koebner phenomenon has a role in the local clearance of ccv following biopsy or other therapies. conflict of interest disclosures: none funding: none corresponding author: nellie konnikov, md, faad jamaica plain veterans affairs medical center department of dermatology 150 s huntington ave boston, ma 02130 email: nellie.konnikov@va.gov references: 1. salama s, rosenthal d. cutaneous collagenous vasculopathy with generalized telangiectasia: an immunohistochemical and ultrastructural study. j cutan pathol. 2000;27(1):40-8. doi:10.1034/j.1600-0560.2000.027001040.x. 2. knöpfel n, martín-santiago a, saus c, escuderogóngora mm, del pozo lj, gómez c. extensive acquired telangiectasias: comparison of generalized essential telangiectasia and cutaneous collagenous vasculopathy. actas dermosifiliogr. 2017;108(3):e21-e26. english, spanish. doi: 10.1016/j.ad.2016.02.020. 3. stavrou c, uthayakumar a, calonje je, bunker cb. cutaneous collagenous vasculopathy. bmj case rep. 2021;14(3):e241434. doi: 10.1136/bcr-2020-241434 4. salama s, chorneyko k, belovic b. cutaneous collagenous vasculopathy associated with intravascular occlusive fibrin thrombi. j cutan pathol. 2014;41(4):386–93. doi: 10.1111/cup.12285. 5. bondier l, tardieu m, leveque p, challende i, pinel n, leccia mt. cutaneous collagenous discussion conclusion skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 428 vasculopathy: report of two cases presenting as disseminated telangiectasias and review of the literature. am j dermatopathol. 2017;39(9):6828. doi:10.1097/dad.0000000000000613. 6. echeverría b, sanmartín o, botella-estrada r, vitiello m. cutaneous collagenous vasculopathy successfully treated with pulsed dye laser. int j dermatol. 2012;51:1359-62. doi:10.1111/j.13654632.2011.05237.x. 7. mitteldorf c, joest b, tronnier m. cutaneous collagenous vasculopathy remission of perivascular deposits after pulsed dye laser therapy. j dtsch dermatol ges. 2017;15(9):9368. doi:10.1111/ddg.13311. 8. grossman me, cohen m, ravits m, blume r, magro cm. cutaneous collagenous vasculopathy: a report of three cases. j cutan pathol. 2022;49(5):491-495. doi: 10.1111/cup.14192. 9. weisert e, hoyer p, arnold m, goodwin b. clinical improvement of cutaneous collagenous vasculopathy with intense pulsed light therapy. dermatol surg. 2021;47(10):1410-1. doi: 10.1097/dss.0000000000003190. 10. basso d, ribero s, blazek c, dietrich n, beltraminelli h, ramelet aa, borradori l, adatto m. cutaneous collagenous vasculopathy: a rare form of microangiopathy successfully treated with a combination of multiplex laser and optimized pulsed light with a review of the literature. dermatology. 2016;232(1):107-11. doi: 10.1159/000439126. 11. camargo cm, brotas am, ramos-e-silva m, carneiro s. isomorphic phenomenon of koebner: facts and controversies. clin dermatol. 2013;31(6):741-9. doi: 10.1016/j.clindermatol.2013.05.012. pmid: 24160280. 12. yadav s, de d, kanwar aj. reverse koebner phenomenon in leukocytoclastic vasculitis. indian j dermatol. 2011;56(5):598-599. doi:10.4103/0019-5154.87169 acknowledgements: medical writing support was provided by prescott medical communications group (chicago, il) with financial support from ortho dermatologics; ortho dermatologics is a division of bausch health us, llc • presented at the 2022 fall clinical dermatology conference • october 20-23, 2022 • las vegas, nv number needed to treat (nnt) what is nnt? � nnt is a metric for quantifying effect sizes of clinically relevant study endpoints1 � nnt represents the number of patients needed to treat to achieve an additional cure in a given timeframe1-3 • for example, nnt=3 means that 3 patients would need to be treated with active drug rather than vehicle before expecting an additional responder2 how is nnt used? � in the absence of head-to-head studies, nnt may be used to indirectly assess comparative efficacy of treatments • evaluation of nnt has been conducted in a variety of therapeutic areas, including psychiatry/neurology, cardiology, oncology, and dermatology � while a clinically relevant nnt threshold has not been established for acne, lower values indicate more favorable treatment (larger effect size) versus vehicle how is nnt calculated? � nnt is the reciprocal of the absolute risk reduction (arr), rounded up to the nearest whole number1-3 what are some limitations of nnt? evaluates one binary outcome (eg, week 12 treatment success)2,4 no consideration of drug tolerability or study design/ population differences1-4 clinical meaning subject to interpretation5 bene�ts of a welldesigned vehicle subtracted from active treatment,a leading to higher nnt values adue to the potential of a well-designed vehicle to result in higher efficacy rates in the control group. benefit of topical combination therapy for acne treatment: analysis of effect size using number needed to treat steven r feldman, md, phd1; george han, md, phd2; valerie callender, md3,4; leon h kircik, md2,5,6; linda stein gold, md7; neal bhatia, md8; stephen k tyring, md, phd9; joshua a zeichner, md2 1wake forest school of medicine, winston-salem, nc; 2icahn school of medicine at mount sinai, new york, ny; 3howard university college of medicine, washington, dc; 4callender dermatology and cosmetic center, glenn dale, md; 5indiana university medical center, indianapolis, in; 6physicians skin care, pllc, dermresearch, pllc, and skin sciences, pllc, louisville, ky; 7henry ford hospital, detroit, mi; 8therapeutics clinical research, san diego, ca; 9university of texas health science center, houston, tx nnts for combination topical acne treatments conclusions � given the paucity of head-to-head studies in acne, nnt may be used as a simple way to compare drug effects across clinical trials � idp-126 gel (clindamycin phosphate 1.2%, bpo 3.1%, adapalene 0.15%) had the most favorable nnt values (lowest), with treatment success rates of ~50% � due to the multifactorial pathogenesis of acne, a triple-combination topical treatment may result in clinical success more often than seen with two-ingredient combination products • these nnt values are supported by phase 2 study results, in which idp-126 led to significantly greater treatment success rates at week 12 compared with its three component dyads in the same vehicle formulation7,8 abbreviations adap, adapalene; bpo, benzoyl peroxide; clin, clindamycin phosphate; egss, evaluator’s global severity scale; iga, investigator’s global assessment; il, inflammatory lesions; nil, noninflammatory lesions; nnt, number needed to treat; tret, tretinoin. references 1. citrome l, ketter ta. int j clin pract. 2013;67(5):407-11. 2. citrome l. j clin psychiatry. 2011;72(3):412-3. 3. manriquez jj, et al. j am acad dermatol. 2007;56(4):664-71. 4. mcalister fa. cmaj. 2008;179(6):549-53. 5. nguyen c, et al. explor res clin soc pharm. 2021;2:100039. 6. drugs@fda: fda-approved drugs. https://www.accessdata.fda.gov/scripts/cder/daf/ 7. stein gold l, et al. presented at the annual american academy of dermatology meeting. march 25-29, 2022. 8. stein gold l, et al. am j clin dermatol. 2022;23(1):93-104. author disclosures srf has received research, speaking and/or consulting support from eli lilly, glaxosmithkline/stiefel, abbvie, janssen, alovtech, vtv therapeutics, bristol-myers squibb, samsung, pfizer, boehringer ingelheim, amgen, dermavant, arcutis, novartis, novan, ucb, helsinn, sun pharma, almirall, galderma, leo pharma, mylan, celgene, ortho dermatologics menlo, merck & co, qurient, forte, arena, biocon, accordant, argenx, sanofi, regeneron, the national biological corporation, caremark, teladoc, eurofins, informa, uptodate and the national psoriasis foundation. he is founder and part owner of causa research and holds stock in sensal health; gh is or has been an investigator, consultant/advisor, or speaker for abbvie, athenex, boehringer ingelheim, bond avillion, bristol-myers squibb, celgene, eli lilly, novartis, janssen, leo pharma, mc2, ortho dermatologics, pellepharm, pfizer, regeneron, sanofi genzyme, sun pharma, and ucb; vc has served as an investigator, consultant, or speaker for abbvie, galderma, l’oréal, ortho dermatologics, and vyne; lhk has acted as an investigator, advisor, speaker, and consultant for ortho dermatologics; lsg has served as investigator/consultant or speaker for ortho dermatologics, leo pharma, dermavant, incyte, novartis, abbvie, pfizer, sun pharma, ucb, arcutis and lilly; nb has served as advisor, consultant, and investigator for abbvie, almirall, biofrontera, bi, brickell, bms, epi health, ferndale, galderma, incyte, isdin, j&j, laroche-posay, leo pharma, ortho dermatologics, regeneron, sanofi, sunpharma, verrica, and vyne; skt has acted as an investigator for ortho dermatologics; jaz has served as advisor, consultant, or speaker for abbvie, allergan, dermavant, dermira, epi health, galderma, incyte, johnson and johnson, l’oreal, ortho dermatologics, pfizer, procter and gamble, regeneron, sun pharma, ucb, unilever, and vyne. objectives and methods � the objective was to evaluate nnt values for combination topical acne treatments � nnt to achieve treatment success was calculated for 8 combination treatments: 7 dual-combinations (fda approved) and 1 triple-combination (in development) � treatment success was defined as ≥2-grade egss/iga improvement and clear/almost clear skin at week 12 results � treatment success rates and calculated nnt values from 13 studies are shown in the figure • eleven studies enrolled patients with moderate-to-severe acne and 2 studies included those with mild and/or very severe acne; additional inclusion/exclusion criteria are shown � the lowest nnt values (most favorable) were achieved with idp-126 gel—fixed-dose, triple combination clindamycin phosphate 1.2%, bpo 3.1%, adapalene 0.15%—which is in development for the treatment of acne idp-126 gel clin 1.2%, bpo 3.1%, adap 0.15% treatment success (%)a nnt (calculated) favors treatment severityc age, y il nil 3, 4 ≥9 30-100 35-150 3, 4 ≥12 20-100 30-150 3 2, 3, 4 ≥12 20-50 30-100 3, 4 12-70 17-40 20-100 2, 3, 4, 5 ≥12 17-40 20-150 3, 4 12-70 20-40 20-100 3, 4 ≥9 20-100 30-150 3, 4 ≥12 20-100 20-100 epiduo forte gel adap 0.3%, bpo 2.5% epiduo gel adap 0.1%, bpo 2.5% acanya gel clin 1.2%, bpo 2.5% veltin gel clin 1.2%, tret 0.025% onexton gel clin 1.2%, bpo 3.75% twyneo cream tret 0.1%, bpo 3% ziana gel clin 1.2%, tret 0.025% 20.5 50.5 24.9 49.6 11.0 33.7 11.3 30.1 5.6 21.5 14.4 28.8 10.8 28.4 17.8 33.2 14.5 28.5 14.3 39.9 15.1 26.8 7.9 22.8 8.7 21.0 vehicle active treatment 5 4 5 7 6 7 6 7 8 9 4 9 7 inclusion/exclusion criteriab adefined as percentage of patients achieving ≥2-grade reduc tion from baseline in egss/iga and clear/almost clear skin at week 12. data for approved treatments were from prescribing information and/or fda medical reviews.6 data for idp-126 were from t wo phase 3 studies.7 binclusion/exclusion criteria were for facial acne or were not specified. cstudies evaluated severit y via 5or 6 -point egss or iga. though there were slight dif ferences in definition, generally: 0=clear, 1=almost clear/minimal, 2=mild, 3=moderate, 4=severe, 5=ver y severe. 1 (% success with active treatment − % success with vehicle) * 100 acknowledgements study funded by sol-gel technologies ltd.; poster support provided by galderma laboratories, l.p., fort worth, tx eps.p-sgt5401-03 drug microencapsulation background benefits of microencapsulation • creates a silicon dioxide (silica) microcapsule shell between the bpo and the skin5 • helps control the release rate of the drug to improve tolerability6 • can preserve the advantages of bpo while minimizing limitations6 encapsulation process4 silica is added in 5–100 repetitive cycles to build up a silica shell around the bpo 47.4 20.7 49.2 28.2 0 15 30 pe rc en ta ge o f s ub je ct s ac hi ev in g ig a su cc es s (it t) 45 60 e-bpo (n=243) 95% ci: 16.7%, 36.8% 95% ci: 10.7%, 31.3% vehicle (n=118) e-bpo (n=250) vehicle (n=122) study 1 study 2 m ea n in fla m m at or y le si on c ou nt ch an ge f ro m b as el in e e-bpo cream 5% (n=243) p <.001 p <.001 p <.001 vehicle (n=118) -20 -18 -16 -14 -12 -10 -8 -6 -4 -2 0 baseline week 2 week 4 week 8 week 12 -10.5 -5.5 -14.6 -8.7 -16.8 -10.6 -17.4 -9.5 p <.001 m ea n in fla m m at or y le si on c ou nt ch an ge f ro m b as el in e (it t) e-bpo cream 5% (n=243) p <.001 p <.001 vehicle (n=118) e-bpo cream 5% (n=250) vehicle (n=122) study 1 study 2 -17.4 -9.5 -20.3 -13.3 -25 -20 -15 -10 -5 0 m ea n in fla m m at or y le si on c ou nt ch an ge f ro m b as el in e p <.001 p <.001 p <.001 p <.001 baseline week 2 week 4 week 8 week 12 0 5 10 15 20 25 30 35 -13.0 -8.0 -16.7 -10.5 -20.0 -12.4 -20.3 -13.3 e-bpo cream 5% (n=250) vehicle (n=122) introduction • rosacea affects at least 10% of fair skinned individuals and not uncommon in black, asian, and hispanic populations1,7,8 • over 16 million people in the united states have rosacea2 • triggers for rosacea are wide-ranging and can include skin care products, cold and/or hot weather, spicy foods, and emotional stress1 • rosacea is characterized as an inflammatory disorder of the facial skin that primarily affects the cheeks, nose, chin, forehead, and eyes1 • rosacea signs present as facial erythema, flushing, papules, pustules, phymas, and telangiectasias1,7 • the disease is frequently characterized by remissions and exacerbations1 critical evaluation of benzoyl peroxide in rosacea: old challenges and new clinical opportunities with encapsulated benzoyl peroxide james q. del rosso, do1; neal d. bhatia, md2; hilary baldwin, md3; linda stein gold, md4; seemal r. desai, md5,6; sam brantman, pharmd7 1jdr dermatology research, las vegas, nv; 2therapeutics clinical research, san diego, ca; 3the acne treatment & research center, brooklyn, ny, and rutgers robert wood johnson medical center, new brunswick, nj; 4henry ford health systems, detroit, mi; 5innovative dermatology, plano, tx; 6department of dermatology, the university of texas southwestern medical center, dallas, tx; 7galderma laboratories, l.p., fort worth, tx methods co-primary endpoints • proportion of subjects with the primary measure of success, “clear” (0) or “almost clear” (1), in the investigator global assessment (iga) relative to baseline at week 12 the iga scale ranged from “clear” (0) to “severe” (4) and included the number of papules/pustules and erythema severity • absolute mean change in inflammatory lesion counts from baseline to week 12 secondary endpoints • percentage change in inflammatory lesion count from baseline to week 12 • absolute change in inflammatory lesion count from baseline to week 8 study design of the two pivotal phase 3 trials for e-bpo cream, 5% (figure 1) references 1. thiboutot d, anderson r, cook-bolden f, et al. standard management options for rosacea: the 2019 update by the national rosacea society expert committee. j am acad dermatol. jun 2020;82(6):1501-1510. 2. van zuuren ej. rosacea. n engl j med. 2017 nov 2;377(18):1754-1764. 3. tan j, steinhoff m, bewley a, et al. [published correction appears in in j dermatolog treat. 2020;31(2):210]. j dermatolog treat. 2020;31(2):168-174. 4. steinhoff m, et al. beyond the visible: rosacea and psoriasis of the face. the bmj hosted content 2020. accessed april 2021. https://hosted.bmj.com/media/images/beyond-the-visible-rosacea-andpsoriasis-of-the-face.pdf. 5. kolli ss, pecone d, pona a, et al. topical retinoids in acne vulgaris: a systematic review. am j clin dermatol. 2019 jun;20(3):345-365. 6. rosacea now estimated to affect at least 16 million americans. national rosacea society. winter 2010. accessed october 19, 2021. https://www.rosacea.org/rosacea-review/2010/winter/rosaceanow-estimated-to-affect-at-least-16-million-americans. 7. del rosso jq, tanghetti e, webster g, et al. update on the management of rosacea from the american acne & rosacea society (aars). j clin aesthet dermatol. 2019 jun;12(6):17-24. 8. gallo rl, granstein rd, kang s, et al. standard classification and pathophysiology of rosacea: the 2017 update by the national rosacea society expert committee. j am acad dermatol. 2018 jan;78(1):148-155. 9. erlich m, arie t, koifman n, et al. structure elucidation of silica-based core-shell microencapsulated drugs for topical applications by cryogenic scanning electron microscopy. j colloid interface sci. 2020 nov 1;579:778-785. 10. fireman s, toledano o, neimann k, et al. a look at emerging delivery systems for topical drug products. dermatol ther. 2011 sep-oct;24(5):477-88. summary • both phase 3 studies met the co-primary endpoints of iga success “clear” (0) or “almost clear” (1) (p <.02) and a significant reduction in the absolute mean change in inflammatory lesion counts (p <.001) versus vehicle at 12 weeks • e-bpo cream, 5%, had a well-tolerated safety profile similar to vehicle in both studies • a reduction in mean inflammatory count was seen as early as week 2 in both studies and was maintained for the entirety of each 12-week study results • a reduction in mean inflammatory count was seen as early as week 2 in both studies and was maintained for the entirety of each 12-week study (figure 4) • most subjects experienced adverse reactions that were mild or moderate in severity (table 3) • the serious adverse event reported in the treatment arm was determined by the investigators to not be related to study drug • teaes are combined from study 1 and study 2 study 1 study 2 characteristic e-bpon=243 vehicle n=118 e-bpo n=250 vehicle n=122 iga: moderate 210 (86.4%) 104 (88.1%) 227 (90.8%) 112 (91.8%) iga: severe 33 (13.6%) 14 (11.9%) 23 (9.2%) 10 (8.2%) mean lesion count (sd) 25.7 (11.07) 26.3 (12.45) 29.8 (14.00) 27.5 (13.04) median lesion count (range) 22.0 (15–69) 21.0 (15–70) 25.0 (15–70) 22.5 (15–70) mean age (years) 52.8 52.4 49.5 51.5 male 60 (24.7%) 35 (29.7%) 69 (27.6%) 35 (28.7%) female 183 (75.3%) 83 (70.3%) 181 (72.4%) 87 (71.3%) grade description 0 – clear skin clear of inflammatory papules or pustules 1 – almost clear very few small papules or pustules and very mild dull erythema are present 2 – mild few small papules or pustules and mild dull or light pink erythema are present 3 – moderate several to many small or larger papules or pustules and moderate light to bright red erythema are present 4 – severe numerous small and/or larger papules or pustules and severe erythema that is bright red to deep red are present e-bpo (n=488) vehicle (n=234) subjects reporting any teae 99 (20.3%) 39 (16.7%) serious teae 1 (0.2%) 1 (0.4%) discontinued study drug 11 (2.3%) 3 (1.3%) discontinued study 9 (1.8%) 2 (0.9%) related aes occurring in >1% of subjects treated with e-bpo application site pain 11 (2%) 2 (1%) application site erythema 11 (2%) 2 (1%) application site pruritis 6 (1%) 1 (<1%) application site edema* 4 (1%) 0 (0%) *application site edema includes application site swelling and application site edema. table 3. treatment-emergent adverse events (safety population) figure 1. two phase 3, double-blind, randomized, vehicle-controlled studies figure 5. iga success with e-bpo — study 1 subject 101021 figure 2. iga success at week 12 figure 4. mean inflammatory lesion count change from baseline figure 3. mean inflammatory lesion count change from baseline to week 12 e-bpo cream, 5% e-bpo cream, 5% (once daily) vehicle cream (once daily) 12 weeks of treatment • men and women ≥18 years of age • clinical diagnosis of moderate to severe rosacea with a baseline investigator global assessment score of 3 or 4 • ≥15 to ≤70 inflammatory lesions • ≤2 nodules randomization qd, self-applied 54 total study sites study 1 e-bpo: n=243 vehicle: n=118 study 2 e-bpo: n=250 vehicle: n=122 ke y in clu sio n cr ite ria baseline 2 4 8 12 weeks • in both studies, e-bpo cream, 5%, demonstrated statistically significant improvement in the co-primary endpoint of the number of subjects achieving “clear” or “almost clear” • in study 1, 47.4% of subjects treated with e-bpo achieved iga success at week 12 versus 20.7% of subjects treated with vehicle. in study 2, it was 49.2% versus 28.2% of subjects (figure 2) • in both studies, e-bpo demonstrated a significant reduction in inflammatory lesion counts from baseline to week 12 versus vehicle (figure 3) study 1 study 2 baseline iga 3 3 3 1 inflammatory lesions 20 23 12 7 iga 4 4 4 3 inflammatory lesions 68 25 33 21 week 4 week 8 week 12 co-primary endpoint least squares means, standard deviations, and treatment p value from an analysis of covariance with factors of treatment group, analysis center, and treatment by analysis center interaction and baseline lesion count as a covariate. negative least squares means values represent decrease from baseline. 2:1 table 1. baseline characteristics of subjects table 2. investigator global assessment (iga) scale abbreviations: e-bpo = encapsulated benzoyl peroxide; iga = investigator global assessment; itt = intent-to-treat; sd = standard deviation; teae = treatment-emergent adverse event week 4 week 8 week 12 figure 6. iga failure with e-bpo — study 1 subject 106017 baseline skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 374 clinical management recommendations transitioning between biologics ronald vender, md, frcpc1 1dermatrials research inc., hamilton, on, canada transitioning between biologics, also known as switching or changing between biologics, is not a new phenomenon. since biologics for moderate to severe psoriasis have been available, physicians have been required to think about how, when, what and whom to switch. a treating physician, along with the patient, must have an agreed-upon treatment target or goal. the ultimate goal, in most cases, however, could be complete disease clearance, although pasi 75 has been considered an acceptable goal by previous authors.1 in order to achieve this, or at least as close as possible with the tools available, continuous, discussions, assessments and potential modifications should be done during patient visits. these modification strategies include dose adjustments, reduction of dose intervals, adjuvant topical or systemic therapies, or changing the biologic.1 this short paper focuses on the last strategy: abstract background: transitioning between biologics has become an important part of practice. objective: patients with moderate to severe plaque psoriasis who are on biologics can have efficacy failures, as well as safety concerns. this would often necessitate a change of biologic, which may be within the same class or to a different class. a change due to an adverse event from the presently used biologic may resolve or require treatment until a new biologic is introduced, which may pose some delay in the initiation of the subsequent biologic. methods: a review of the literature and guidelines published were performed. results: a practical guide to transitioning between biologics are presented limitations: there are no randomized placebo-controlled trials comparing transitioning to different biologics to determine the best method of transitioning. conclusion: transitioning between biologics is an option for those patients requiring such a change either for safety or efficacy reasons. introduction skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 375 changing, switching or transition between biologics. when considering a change, one must also consider the functional impairment of the patient, comorbidities, as well as treatment risks.2 for instance, not all biologics are indicated for psoriatic arthritis, while others must be used with caution in patients with inflammatory bowel disease (a known comorbidity associated with psoriasis). some biologics can be administered via alternative devices (e.g. auto-injectors) to simplify selfinjection in patients that may have dexterity issues. primary non-response, secondary nonresponse, adverse events, and the patientphysician decision may also be factors for switching therapy.3 primary non-response is also well known as a primary failure. this can occur in a small percentage of patients with any biologic. in the past, a pasi response of less than 75% improvement was considered primary failure if the success was not seen in the first six months of treatment. more recently, due to the greater efficacy of newer biologics, a pasi response of less than 90% improvement may be considered a primary failure. this can be considered as early as the first 8-12 weeks.4,5 some treating physicians may be a bit more patient and stretch it to the first 4-6 months. while a lack of initial efficacy during the induction period may be considered primary failure, given the variation of induction periods with many biologics, this may be an inadequate time to reach a conclusion. secondary non-response is also known as secondary failure, where there is a loss of efficacy over time. several possible contributing factors include a patient’s weight, previous biologic failures, and comorbidities (e.g. psoriatic arthritis, diabetes, hypertension and cardio-metabolic disease). occasionally, optimization of the biologic, such as increasing the dose or shortening the intervals between treatments, may boost efficacy. a new concept of reinduction may also help to reverse a secondary failure.6,7 adverse events may necessitate a change in biologics as well. examples include the development of tuberculosis, multiple sclerosis, congestive heart failure, recurrent candidiasis and/or sinusitis and injection site reactions. lastly, patient-physician decision, such as a request for switching for reasons other than efficacy or safety, can occur. however, undisclosed non-adherence may be thought of as non-response to treatment and could lead to switching therapies unnecessarily.8,9 there are differences of opinions as to whether washouts are required in-between different biologics. appropriate washout periods minimize the potentially adverse safety effects of treating with two immunomodulatory agents at once. evidence against a washout appreciates the risk to the patient’s quality of life of waiting for 4 halflives between biologics. the latter may outweigh any perceived benefit.10,11 the risk for psoriasis flares is generally greater than the risk for any adverse effects associated with overlapping biologic therapies.12 while a theoretical risk for increased susceptibility to infection has been proposed if washout time is not adequate between biologic therapies, data supporting such a risk are minimal.13 time for something new washouts skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 376 there are many published guidelines for treating psoriasis, however very few provide guidance on how to transition between biologics. the guidelines from spanish academy of dermatology and venereology (aedv) recommend that when switching to consider the following: presence or absence of active joint disease, the clinical characteristics of the patient (weight, risk of infection, comorbidities, and contraindications related to specific biologic agents), the mechanism of action, the appropriateness of the dosage and route of administration, the additional cost of induction therapy and other pharmacoeconomic considerations, the relative risk of infections and immunogenicity and the response of the new biologic with previous exposure or failures of other biologics. however, no guidance was given on exactly how to transition.14 the joint aad-npf guidelines suggest switching biologics when there is no definitive response to treatment with anti-il12/23, antiil17s and anti-il23s ascertained after 12 weeks of continuous therapy, anti-tnfs after 12-16 weeks of continuous therapy and infliximab after 8-10 weeks. if clinically needed, it is suggested, to switch to a different biologic agent with the possibility of improved efficacy, safety, and/or tolerability. they warn that not all switches may result in improvement. the duration of the interval between discontinuation of previous medication and initiation of a biologic may depend on the treatment that is being discontinued, disease severity, and response to prior treatment, therefore, should be assessed on a case-by-case basis. similar to aedv guidelines, no direction on exactly how to switch is discussed.15 the national institute for health and care excellence (nice) guidelines, recommend a switch if there is 1) no adequate response to a first biologic (at 10 weeks after starting infliximab, 12 weeks for etanercept, ixekizumab, secukinumab and brodalumab, and 16 weeks for adalimumab, ustekinumab, or guselkumab; primary failure) or 2) psoriasis initially responds adequately but subsequently loses this response (secondary failure), or 3) the 1st biologic cannot be tolerated or becomes contraindicated. again, there is no guidance on how to transition.16 the most definitive guidelines on transitioning between biologics belong to the british association of dermatologists (bad).7 they suggest the following transitioning options: no washout period or a nonstandard washout period (greater than or less than three months or four half-lives). an overlap of biologic therapy or bridging with standard systemics may also be considered. no studies comparing strategies for transitioning between biologic therapies were included in the clinical review. in those that used shorter, non-standard washout periods, there did not appear to be an increased safety risk. the bad guidelines note factors that influence transitioning therapy strategies: drug pk/pd of the drug being stopped and the one to be started, the patient’s clinical history, the disease severity and the underlying risk of infection (if biologics are overlapped). finally, recommendation r27 suggests the following: when transitioning to a new biologic therapy (from a previous biologic therapy) consider using: a 1-month washout period or the length of the treatment cycle (whichever is longer) between the last dose of the current biologic therapy and the planned date of biologic initiation. guidelines skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 377 when switching due to efficacy, one can use no washout by switching at the next scheduled dose of the failed biologic based on the minimal or shortest dosing interval of the failed biologic with the standard induction dose schedule followed by standard maintenance dosing of the subsequent biologic.6 however, when switching due to safety issues, one may need to use a necessary treatment-free interval until safety parameters have normalized or stabilized.6 the washout period for biologics is usually considered to be four half-lives of the reference drug. it is important to realize that the pharmacodynamic effects of the biologic may not necessarily correlate with the pharmacokinetic effects.7,11,17 when no washout period is required then the guide in table 1 is suggested. note the table accounts for usual dosing, but if patients are switched without washouts of the prior drug, adverse outcomes have not been reported i.e. they could stop a drug on one day and take another the next day. table 1. the guide based on minimum dosing intervals failed biologic could start a new biologic in… etanercept 1 week1 adalimumab 2 weeks1 infliximab 2-4 weeks1 certolizumab 2 weeks2 ustekinumab 4 weeks2 secukinumab 2 weeks2 ixekizumab 2 weeks2 brodalumab 2 weeks2 guselkumab 4 weeks2 tildrakizumab 4 weeks2 risankizumab 4 weeks2 1mrowietz, u., de jong, e., kragballe, k., et al. a consensus report on appropriate treatment optimization and transitioning in the management of moderate‐to‐severe plaque psoriasis. j eur acad dermatol venereol. 2014;28: 438453. 2extrapolated from mrowietz, u., de jong, e., kragballe, k., et al. a consensus report on appropriate treatment optimization and transitioning in the management of moderate‐to‐severe plaque psoriasis. j eur acad dermatol venereol. 2014;28:438-453. how to transition skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 378 in general, reports show that switching between biologics whether within the same class or to a different class can be successful. 17 however, piaserico et al. noted that individuals who experienced a secondary loss of efficacy to one tnf inhibitor or stopped treatment due to an adverse event were more likely to achieve pasi 75 at week 12 than those who were primary nonresponders.3 the first reported transitioning between two anti-il-17 antagonists showed similar efficacy when brodalumab patients were transitioned to secukinumab with a twomonth washout period. there was no primary, secondary, or safety issue in the brodalumab patients. the reason for the switch was due to the abrupt cessation of a clinical trial of brodalumab for administrative reasons.18 in contrast to piaserico et al.3 , georgakopoulos et al. 19 showed that the same might not be true for il-17a antagonists, where efficacy outcomes did not correlate with reason for secukinumab discontinuation and the duration of secukinumab therapy had no effect on efficacy outcomes when switched to ixekizumab in their case series. more specifically, in this canadian multicentre retrospective study of 17 secukinumab nonresponders, there were 4 primary secukinumab non-responders whom all responded to ixekizumab, reaching pasi75 or a physician’s global assessment (pga) of 0 or 1. there were 9 secondary nonresponders to secukinumab where 8 of the 9 responded to ixekizumab with a pasi75 or pga of 0 or 1. there were 4 patients who stopped secukinumab due to intolerance or non-drug related reasons and 3 were able to achieve a pasi75 or pga of 0 or 1 on ixekizumab. overall, their results suggested that a large proportion of secukinumab non-responders who switched to ixekizumab will experience an improved clinical response regardless of the reason or timing of secukinumab discontinuation. not all patients who experienced an adverse event to secukinumab will experience the same issue with ixekizumab but could experience new adverse events as well. it may be worth noting, especially with the secondary nonresponders, that the primary outcome of this study was taken at the end of the ixekizumab loading phase (week 12), which is obviously a higher dose than during the maintenance phase. as secondary non-responders to secukinumab, they would have also responded well during the induction phase of this biologic and therefore it is still possible that these patients will be secondary nonresponders to ixekizumab when observed at later time points on the label maintenance dose. gasslitter, i., et al,20 also recently showed successful switching in 26 patients between the three presently available anti-il-17 agents (secukinumab, ixekizumab and brodalumab). eighteen patients changed their treatment from secukinumab to ixekizumab and seven patients to brodalumab. brodalumab was used in 3 cases after the failure of treatment with ixekizumab. in only one case, did the nonresponse of brodalumab result in a therapy switch to secukinumab. overall success was seen in over 70% of patients. finally, a clinical benefit has also been observed among patients who switched from an anti-il12/23 inhibitor (ustekinumab) to an anti-il23 inhibitor (guselkumab). specifically, a phase 3 study showed that guselkumab what to transition to skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 379 demonstrated greater efficacy compared with ustekinumab among patients who failed to achieve an investigator’s global assessment score of 0 or 1 with ustekinumab therapy. for example, at week 52, greater proportions of patients treated with guselkumab achieved pasi 90 (51.1% vs. 24.1%; p < 0.001) and pasi 100 (20.0% vs. 7.5%; p = 0.003) compared with the randomized ustekinumab group.21 similarly, a phase 2 study showed that patients who have been previously treated with ustekinumab, when re-treated with risankizumab, maintained or improved pasi 90 response rates.22 overall, regardless of the biologic, switching agents can significantly improve outcomes for patients.23 transitioning between biologics is now a privilege and a better way to optimize treatment for patients with moderate to severe psoriasis to improve their quality of life. conflict of interest disclosures: ron vender has served on advisory board and consultant and principal investigator and speaker for abbvie, amgen, bausch-health, celgene, centocor, janssen, lilly, merck, novartis, pfizer, and ucb funding: none corresponding author: ron vender, md, frcpc dermatrials research inc. 707-25 charlton ave east hamilton on l8n 1y2 tel: (905) 517-8119 email: ron.vender@me.com references: 1. mrowietz u, kragballe k, reich k, et al. definition of treatment goals for moderate to severe psoriasis: a european consensus. arch dermatol res. 2010;303(1):1-10. 2. gladman d, poulin y, adams k, et.al. treating psoriasis and psoriatic arthritis: position paper on applying the treat-to-target concept to canadian daily practice. the journal of rheumatology. apr 2017;44(4):519-534. 3. piaserico, stefano et al. efficacy of switching between tumor necrosis factor-alfa inhibitors in psoriasis: results from the italian psocare registry. j am acad dermatol. 2014;70(2):257262.e3. 4. mrowietz, u. , steinz, k. and gerdes, s., psoriasis: to treat or to manage? exp dermatol. 2014;23:705-709. doi:10.1111/exd.12437 5. gulliver, w., lynde, c., dutz, j. et al. think beyond the skin. 2014 canadian expert opinion paper on treating to target in plaque psoriasis. journal of cutaneous medicine and surgery. 2015:19(1);22–27. https://doi.org/10.2310/7750.2014.13151 6. mrowietz, u. , de jong, e. , kragballe, k. , et al. a consensus report on appropriate treatment optimization and transitioning in the management of moderate‐to‐severe plaque psoriasis. j eur acad dermatol venereol. 2014;28:438-453. 7. smith, c., jabbar‐lopez, z., yiu, z., et al. british association of dermatologists guidelines for biologic therapy for psoriasis. br j dermatol. 2017;177:628-636. 8. dunbar-jacob, j. et al. treatment adherence in chronic disease. journal of clinical epidemiology. 54(12);s57-s60. 9. ahluwalia, v., rampakakis, e., movahedi, m. et al. predictors of patient decision to discontinue anti-rheumatic medication in patients with rheumatoid arthritis: results from the ontario best practices research initiative. clin rheumatol. 2017;36:2421. https://doi.org/10.1007/s10067-017-3805-4 10. cather jc, crowley jj. use of biologic agents in combination with other therapies for the treatment of psoriasis. am j clin dermatol. 2014;15(6):46778. 11. choi, young m. et al. from the medical board of the national psoriasis foundation: perioperative management of systemic immunomodulatory agents in patients with psoriasis and psoriatic arthritis. j am acad dermatol. 2016;75(4):798805.e7. 12. mrowietz u, kragballe k, reich, et al. definition of treatment goals for moderate to severe psoriasis: conclusion mailto:ron.vender@me.com https://doi.org/10.1111/exd.12437 skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 380 a european consensus. j eur acad dermatol venereol. 2011;25(suppl 3):1–13. 13. downs, a. observational case series on a group of patients with severe psoriasis who failed to respond to antitumour necrosis factor α biologics and switched to ustekinumab. br j dermatol. 2010;163:433-434. 14. puig, et al. spanish evidence-based guidelines on the treatment of psoriasis with biologic agents. part 1: on efficacy and choice of treatment. actas dermo-sifiliográficas (english edition). oct 2013;104(8):694-709. 15. menter a, strober b, kaplan d, et al. joint aadnpf guidelines of care for the management and treatment of psoriasis with biologics. j am acad dermatol. 2019;80(4):1029-1072. 16. national institute for health and care excellence, nice guidelines. oct 2012-updated dec 2017;sec1.5.3.4 psoriasis: assessment and management. 17. leman, j. and burden, a. sequential use of biologics in the treatment of moderate‐to‐severe plaque psoriasis. br j dermatol. 2012;167(suppl 3):12-20. 18. vender r. transitioning between brodalumab and secukinumab in moderate to severe psoriasis: an early look. j drugs dermatol. august 2016;15(8):941-43. 19. georgakopoulos jr phung m, ighani, a, et al. efficacy and safety of switching to ixekizumab in secukinumab nonresponders with plaque psoriasis: a multicenter retrospective study of interleukin 17a antagonist therapies. j am acad dermatol. july. 2018;79(1):155-57. 20. gasslitter, i kirsten, n., augustin, m. et al. successful intra-class switching among il-17 antagonists: a multicentre, multinational, retrospective study. arch dermatol res (2019). 21. langley, r. , tsai, t. , flavin, s. , et.al. efficacy and safety of guselkumab in patients with psoriasis who have an inadequate response to ustekinumab: results of the randomized, double‐ blind, phase iii navigate trial. br j dermatol. 2018;178:114-123. 22. clinical response following re-treatment with a selective il-23p19 inhibitor risankizumab (bi 655066) or switching from ustekinumab to risankizumab in patients with moderate-tosevere chronic plaque psoriasis;papp k, et al. (fc03.04; oral session; thursday, september 29, 2016; 1:45-1:55 p.m. cet). 23. hu, y., chen, z., gong, y. et al. a review of switching biologic agents in the treatment of moderate-to-severe plaque psoriasis. clin drug invest. 2018;38:191. deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, in scalp, nail, and palmoplantar psoriasis: subgroup analyses of the phase 3 poetyk pso-1 and pso-2 trials andrew blauvelt,1 phoebe rich,2 howard sofen,3 jo lambert,4 joseph f merola,5 mark lebwohl,6 thomas scharnitz,7 kim hoyt,7 renata m kisa,7 subhashis banerjee7 1oregon medical research center, portland, or, usa; 2oregon dermatology and research center, portland, or, usa; 3ucla school of medicine, los angeles, ca, usa; 4ghent university, ghent, belgium; 5brigham and women’s hospital, brigham dermatology associates, and harvard medical school, boston, ma, usa; 6icahn school of medicine at mount sinai, new york, ny, usa; 7bristol myers squibb, princeton, nj, usa presented at the 2022 fall clinical dermatology conference; october 20—23, 2022; las vegas, nv this poster may not be reproduced without written permission from the authors.email for andrew blauvelt, md, mba: ablauvelt@oregonmedicalresearch.com scientific content on demand to request a copy of this poster: scan qr code via a barcode reader application qr codes are valid for 30 days after congress presentation date introduction • deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 (tyk2) inhibitor, is approved by the us food and drug administration for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy1 — uniquely binds to the regulatory domain instead of the catalytic domain of tyk22 x ≥100-fold greater selectivity for tyk2 vs janus kinase (jak) 1/3 and ≥2000-fold greater selectivity for tyk2 vs jak 2 in cells2,3 — inhibits tyk2-mediated cytokine signaling involved in psoriasis pathogenesis (eg, interleukin-23, type i interferons)2 • two 52-week, phase 3 psoriasis trials (poetyk pso-1 and poetyk pso-2) previously demonstrated that deucravacitinib was superior to placebo and apremilast at week 16 based on the coprimary endpoints4,5: — ≥75% reduction from baseline in psoriasis area and severity index (pasi 75) — static physician’s global assessment score of 0 (clear) or 1 (almost clear) with a ≥2-point improvement from baseline (spga 0/1) • clinical efficacy and overall safety and tolerability were maintained for up to 2 years6 objective • evaluate the efficacy of deucravacitinib treatment in patients with moderate to severe scalp, fingernail, and palmoplantar psoriasis methods study designs • poetyk pso-1 (nct03624127) and pso-2 (nct03611751) enrolled adults with moderate to severe plaque psoriasis (pasi ≥12, spga ≥3, body surface area involvement ≥10%) (figure 1) figure 1. study designs poetyk pso-1 (n = 666) poetyk pso-2 (n = 1020) deucravacitinib 6 mg qdplacebo (n = 166) deucravacitinib 6 mg qd<pasi 50 apremilast 30 mg bid≥pasi 50 titrate* 1 :2 :1 r an d om iz at io n weeks 16 24 520 deucravacitinib 6 mg qdplacebo (n = 255) deucravacitinib 6 mg qd (n = 511) deucravacitinib 6 mg qd<pasi 75 deucravacitinib 6 mg qd<pasi 75 deucravacitinib 6 mg qd deucravacitinib 6 mg qd placebob apremilast 30 mg bida (n = 254) ≥pasi 75 1 :2 :1 r an d om iz at io n weeks 16 24 520 1:1 deucravacitinib 6 mg qdplacebob deucravacitinib 6 mg qd (n = 332) primary endpoint primary endpoint apremilast 30 mg bida (n = 168) ≥pasi 75 aapremilast was titrated from 10 mg qd to 30 mg bid over the first 5 days of dosing. bupon relapse (≥50% loss of week 24 pasi percentage improvement from baseline), patients were to be switched to deucravacitinib 6 mg qd. bid, twice daily; pasi, psoriasis area and severity index; pasi 50, ≥50% reduction from baseline in pasi; pasi 75, ≥75% reduction from baseline in pasi; qd, once daily. outcomes • this analysis looked at scalp-, fingernail-, and palmoplantar-specific outcomes in pooled patients from poetyk pso-1 and pso-2, including: — scalp-specific pga score of 0 or 1 (ss-pga 0/1) and ≥90% reduction from baseline in psoriasis scalp severity index (pssi 90) in patients with moderate to severe scalp psoriasis (ss-pga ≥3) at baseline — pga-fingernails score of 0 or 1 (pga-f 0/1) in patients with moderate to severe fingernail psoriasis (pga-f ≥3) at baseline — palmoplantar pga score of 0 or 1 (pp-pga 0/1) and palmoplantar pasi (pp-pasi) response in patients with moderate to severe palmoplantar psoriasis (pp-pga ≥3) at baseline • outcomes in patients randomized to deucravacitinib vs placebo are reported through week 16, and efficacy in deucravacitinib-treated patients is reported through week 24 • outcomes in patients who crossed over from placebo to deucravacitinib at week 16 are reported from weeks 16 —52 statistical analysis • none of the statistical comparisons of deucravacitinib vs placebo were multiplicity controlled results baseline patient demographics and disease characteristics • in the pooled poetyk pso-1 and pso-2 population (n = 1264; table 1): — 63.9% (n = 808) had moderate to severe scalp psoriasis — 14.6% (n = 184) had moderate to severe fingernail psoriasis — 6.5% (n = 82) had moderate to severe palmoplantar psoriasis • presence of moderate to severe disease in these special areas was balanced overall in the deucravacitinib group vs the placebo group table 1. baseline patient demographics and disease characteristics poetyk pso-1 and pso-2 placebo deucravacitinib parameter (n = 421) (n = 843) age, mean (sd), y 47.5 (13.7) 46.5 (13.5) weight, mean (sd), kg 90.6 (21.1) 90.6 (21.9) female, n (%) 127 (30.2) 277 (32.9) race, n (%) white 360 (85.5) 741 (87.9) asian 42 (10.0) 83 (9.8) other 19 (4.5) 19 (2.3) disease duration, mean (sd), y 18.9 (12.9) 18.6 (12.7) prior systemic treatment use, n (%) yes 248 (58.9) 474 (56.2) nonbiologic (± biologic) 183 (43.5) 326 (38.7) biologic 146 (34.7) 295 (35.0) no 173 (41.1) 369 (43.8) spga, n (%) 3 = moderate 345 (81.9) 665 (78.9) 4 = severe 75 (17.8) 178 (21.1) pasi, mean (sd) 20.9 (8.6) 21.1 (8.0) bsa, mean (sd), % 25.3 (16.1) 26.4 (15.8) ss-pga ≥3, n (%) 294 (69.8) 514 (61.0) pga-f ≥3, n (%) 72 (17.1) 112 (13.3) pp-pga ≥3, n (%) 25 (5.9) 57 (6.8) pssd symptom score, mean (sd) 50.6 (25.6) 52.1 (25.9) dlqi, mean (sd) 11.6 (6.7) 11.9 (6.6) bsa, body surface area; dlqi, dermatology life quality index; pasi, psoriasis area and severity index; pga-f, physician’s global assessment-fingernails; pp-pga, palmoplantar physician’s global assessment; pssd, psoriasis symptoms and signs diary; spga, static physician’s global assessment; ss-pga, scalp-specific physician’s global assessment. scalp psoriasis • significantly more patients receiving deucravacitinib vs placebo achieved ss-pga 0/1 at week 16 (figure 2) — efficacy was significantly greater with deucravacitinib vs placebo by week 1 — ss-pga 0/1 responses at week 16 were maintained through week 24 in deucravacitinib-treated patients figure 2. ss-pga 0/1a responses through week 24 (pooled poetyk pso-1 and pso-2; nri) 0 10 20 30 40 50 ss -p g a 0 /1 r es po n se r at e, % o f pa ti en ts 60 70 80 90 100 0 4 8 12 weeks 16 20 24 64.0%† 64.4% 1 2 17.3% * † † † † primary endpoint placebo (n = 294) deucravacitinib 6 mg qd (n = 514) aincluded patients with a baseline ss-pga score ≥3. *p < 0.05 vs placebo. †p < 0.0001 vs placebo. missing data were imputed with nri. nri, nonresponder imputation; qd, once daily; ss-pga 0/1, scalp-specific physician’s global assessment score of 0 or 1. • significantly more patients receiving deucravacitinib vs placebo achieved pssi 90 at week 16 (figure 3) — efficacy was significantly greater with deucravacitinib vs placebo by week 1 — pssi 90 responses at week 16 were maintained through week 24 in deucravacitinib-treated patients figure 3. pssi 90a responses through week 24 (pooled poetyk pso-1 and pso-2; nri) 0 10 20 30 40 50 p ss i 9 0 re sp on se r at e, % o f pa ti en ts 60 70 80 90 100 0 4 8 12 weeks 16 20 241 2 primary endpoint placebo (n = 294) deucravacitinib 6 mg qd (n = 514) † † † * 50.6%† 10.5% 53.5% * aincluded patients with a baseline ss-pga score ≥3. *p < 0.05 vs placebo. †p < 0.0001 vs placebo. missing data were imputed with nri. nri, nonresponder imputation; pssi 90, ≥90% reduction from baseline in psoriasis scalp severity index; qd, once daily; ss-pga, scalp-specific physician’s global assessment. • in patients who crossed over from placebo to deucravacitinib at week 16, 67.5% achieved ss-pga 0/1 at week 52 (figure 4) and 62.3% achieved pssi 90 at week 52 — these rates were comparable to week 24 findings in patients who received continuous deucravacitinib from day 1 figure 4. ss-pga 0/1a responses through week 52 in placebo crossovers (pooled poetyk pso-1 and pso-2; nri) 1 2 67.5% 0 10 20 30 40 50 ss -p g a 0 /1 r es po n se r at e, % o f pa ti en ts 60 70 80 90 100 0 4 8 12 16 20 24 28 32 36 40 44 48 52 weeks primary endpoint placebo (n = 294) placebo–deucravacitinib (n = 252) aincluded patients with a baseline ss-pga score ≥3. missing data were imputed with nri. nri, nonresponder imputation; ss-pga 0/1, scalp-specific physician’s global assessment score of 0 or 1. fingernail psoriasis • significantly more patients receiving deucravacitinib vs placebo achieved pga-f 0/1 at week 16 (figure 5) — pga-f 0/1 responses at week 16 increased through week 24 in deucravacitinib-treated patients • in patients who crossed over from placebo to deucravacitinib at week 16, 51.6% achieved pga-f 0/1 at week 52 (figure 6) figure 5. pga-f 0/1a responses through week 24 (pooled poetyk pso-1 and pso-2; nri) 32.1% 8.3% 20.5%* 0 10 20 30 40 50 p g a -f 0 /1 r es po n se r at e, % o f pa ti en ts 60 70 80 90 100 0 4 8 12 16 20 24 weeks primary endpoint placebo (n = 112) deucravacitinib 6 mg qd (n = 72) aincluded patients with a baseline pga-f score ≥3. *p = 0.0272 vs placebo. missing data were imputed with nri. nri, nonresponder imputation; pga-f 0/1, physician’s global assessment-fingernails score of 0 or 1; qd, once daily. figure 6. pga-f 0/1a responses through week 52 in placebo crossovers (pooled poetyk pso-1 and pso-2; nri) 51.6% 0 10 20 30 40 50 p g a -f 0 /1 r es po n se r at e, % o f pa ti en ts 60 70 80 90 100 0 4 8 12 16 20 24 28 32 36 40 44 48 52 weeks primary endpoint placebo (n = 72) placebo–deucravacitinib (n = 62) aincluded patients with a baseline pga-f score ≥3. missing data were imputed with nri. nri, nonresponder imputation; pga-f 0/1, physician’s global assessment-fingernails score of 0 or 1. palmoplantar psoriasis • significantly more patients receiving deucravacitinib vs placebo achieved pp-pga 0/1 at week 16 (figure 7) — pp-pga 0/1 responses at week 16 were increased at week 24 in deucravacitinib-treated patients • in patients who crossed over from placebo to deucravacitinib at week 16, 41.2% achieved pp-pga 0/1 at week 52 figure 7. pp-pga 0/1a responses through week 24 (pooled poetyk pso-1 and pso-2; nri) 56.1% 16.0% 49.1%* 0 10 20 30 40 50 pp -p g a 0 /1 r es po n se r at e, % o f pa ti en ts 60 70 80 90 100 0 4 8 12 weeks 16 20 241 2 primary endpoint placebo (n = 25) deucravacitinib 6 mg qd (n = 57) aincluded patients with a baseline pp-pga score ≥3. *p = 0.0052 vs placebo. missing data were imputed with nri. nri, nonresponder imputation; qd, once daily; pp-pga 0/1, palmoplantar physician’s global assessment score of 0 or 1. • mean change from baseline in pp-pasi, adjusted for baseline covariates, was significantly greater with deucravacitinib vs placebo at week 16 (figure 8) — greater efficacy with deucravacitinib vs placebo was observed as early as week 4 — pp-pasi responses at week 16 were maintained through week 24 in deucravacitinib-treated patients figure 8. change from baseline in pp-pasia through week 24 (pooled poetyk pso-1 and pso-2; mbocf) -4.2b -10.7 -13.3* -20 -10 m ea n c fb in p pp a si baseline pp-pasi, mean (sd) placebo (n = 25) deucravacitinib (n = 57) 17.5 (12.5) 15.9 (10.9) 0 0 4 8 12 weeks 16 20 241 2 placebo (n = 25) deucravacitinib 6 mg qd (n = 57) * * * aincluded patients with a baseline pp-pga score ≥3. bdata in placebo crossover patients through week 52 are currently unavailable. *p ≤ 0.0097 vs placebo. missing data were imputed with the mbocf method. cfb, change from baseline; mbocf, modified baseline observation carried forward; pp-pasi, palmoplantar psoriasis area and severity index; pp-pga, palmoplantar physician’s global assessment; qd, once daily. conclusions • in poetyk pso-1 and pso-2 patients with moderate to severe scalp, fingernail, or palmoplantar psoriasis at baseline, deucravacitinib was significantly more efficacious than placebo in improving disease burden in these special high impact areas through week 16, with additional improvements observed in deucravacitinib-treated patients through week 24 • patients who crossed over from placebo to deucravacitinib at week 16 achieved comparable responses at week 52 to those observed at week 24 in patients who had received continuous deucravacitinib treatment from baseline • these findings support the use of deucravacitinib, an oral, selective, allosteric tyk2 inhibitor, in patients with moderate to severe scalp, fingernail, or palmoplantar psoriasis references 1. sotyktu™ (deucravacitinib) [package insert]. princeton, nj, usa: bristol-myers squibb company; september 2022. 2. burke jr, et al. sci transl med. 2019;11:eaaw1736. 3. wrobleski st, et al. j med chem. 2019;62:8973-8995. 4. armstrong aw, et al. j am acad dermatol. 2022;s0190-9622(22)02256-3. doi: 10.1016/j.jaad.2022.07.002. online ahead of print. 5. strober b, et al. j am acad dermatol. 2022;s0190-9622(22)02643-3. doi: 10.1016/j.jaad.2022.08.061. online ahead of print. 6. warren rb, et al. presented at the european academy of dermatology and venereology (eadv) spring symposium; 12—14 may 2022; ljubljana, slovenia. acknowledgments • these clinical trials were sponsored by bristol myers squibb • writing and editorial assistance was provided by liz rockstein, phd, of peloton advantage, llc, an open health company, parsippany, nj, usa, funded by bristol myers squibb disclosures • ab: speaker (received honoraria): abbvie, arcutis, bristol myers squibb, eli lilly, pfizer, regeneron, sanofi, and ucb; scientific adviser (received honoraria): abbvie, abcentra, affibody, aligos, almirall, alumis, amgen, anaptysbio, arcutis, arena, aslan, athenex, bluefin biomedicine, boehringer ingelheim, bristol myers squibb, cara therapeutics, dermavant, ecor1, eli lilly, escient, evelo, evommune, forte bioscience, galderma, highlightii pharma, incyte, innoventbio, janssen, landos, leo pharma, merck, novartis, pfizer, rapt, regeneron, sanofi genzyme, spherix global insights, sun pharma, tll pharmaceutical, trialspark, ucb, vibliome, and xencor; clinical study investigator (institution has received clinical study funds): abbvie, acelyrin, almirall, amgen, arcutis, athenex, boehringer ingelheim, bristol myers squibb, concert, dermavant, eli lilly, evelo, evommune, galderma, incyte, janssen, leo pharma, merck, novartis, pfizer, regeneron, sun pharma, and ucb • pr: research (principal investigator on pharmaceutical trials): abbvie, arcutis, bristol myers squibb, dermavant, eli lilly, janssen, novartis, sun pharma, and ucb • hs: clinical investigator: abbvie, amgen, boehringer ingelheim, bristol myers squibb, eli lilly, janssen, leo pharma, novartis, and sun pharma • jl: unrestricted grants: abbvie, almirall, celgene, eli lilly, janssen-cilag, leo pharma, novartis, and ucb; speaker: abbvie, almirall, bristol myers squibb, janssen-cilag, pfizer, and ucb; consultant: abbvie, bms, celgene, eli lilly, janssen-cilag, leo pharma, novartis, and ucb • jfm: consultant and/or investigator: amgen, abbvie, biogen, bristol myers squibb, dermavant, eli lilly, janssen, leo pharma, novartis, pfizer, regeneron, sanofi, sun pharma, and ucb • ml: research funds on behalf of mount sinai: abbvie, amgen, arcutis, avotres, boehringer ingelheim, dermavant, eli lilly, incyte, janssen, ortho dermatologics, regeneron, and ucb; consultant: aditum bio, almirall, altrubio anaptysbio, arcutis, arena, aristea, arrive technologies, avotres, biomx, boehringer ingelheim, brickell biotech, bristol myers squibb, cara, castle biosciences, corevitas’ (corrona) psoriasis registry, dermavant, dr reddy’s laboratories, evelo biosciences, evommune, forte biosciences, helsinn therapeutics, hexima, leo pharma, meiji seika pharma, mindera, pfizer, seanergy, and verrica • ts, rmk, and sb: employees and shareholders: bristol myers squibb • kh: contractor: bristol myers squibb via syneos health microsoft word muir torre format.doc skin brief articles an interesting case of muir-torre syndrome samuel p. haslam, mda and robert c. smith, mdb a university of texas medical branch, galveston, tx, b denton dermatology, denton, tx abstract muir-torre syndrome is a rare autosomal dominant syndrome that is believed to be a variant of hereditary nonpolyposis colorectal cancer (hnpcc, or "lynch syndrome"), both of which are caused by inherited mutations that impair dna mismatch repair. however, in comparison to lynch syndrome, muir-torre syndrome can be diagnosed in the absence of a family history of malignancies and requires only the presence of a sebaceous tumor and internal malignancy alone. individuals with muir-torre syndrome are prone to colon, breast, and genitourinary tract cancers, as well as cutaneous manifestations such as numerous keratoacanthomas and sebaceous neoplasms. in patients with sebaceous tumors, routine immunohistochemical detection of loss of dna mismatch repair proteins helps to identify hereditary dna mismatch repair deficiency. when the diagnosis of muir-torre syndrome is established, it is advised that both patients and their first-degree relatives follow the same screening criteria for colon cancer and other malignancies as those with lynch syndrome. since sebaceous neoplasms can precede, coincide with, or follow internal manifestations of disease, early identification of muir-torre syndrome is valuable to increase detection of any associated malignancies, and it is also useful to provide counseling for family members at risk for premature malignancies. r.s. is an 83 year old male with a history of multiple non-melanoma skin cancers and a sebaceous adenoma in 2006 who presented with an 8 millimeter, erythematous, hyperkeratotic papule in the medial right eyebrow that was suspicious for a superficial squamous cell carcinoma. however, biopsy revealed sebaceous lobules with a slight increase in thickness of the immature layer of the periphery of the lobule, and the lesion was characterized as a sebaceous adenoma. clinical correlation for muir-torre syndrome was advised, and the patient admitted to a personal history of colon cancer as well as a family history of colon cancer in his father. furthermore, immunoperoxidase stains revealed preservation of staining with msh-2 and msh-6, along with partial loss of staining for mlh-1 and pms-2. given the patient's history of multiple sebaceous neoplasms, personal and family history of colon cancer, and loss of staining with mlh-1 and pms-2, the patient was diagnosed with muir-torre syndrome. his family members were advised to undergo early routine detection for skin and internal cancers given the autosomal dominant july 2017 volume i issue i copyright 2017 the national society for cutaneous medicine 45 case presentation skin july 2017 volume i issue i 46 copyright 2017 the national society for cutaneous medicine nature of the syndrome along with its associated increase in risk for internal and cutaneous cancers. muir-torre syndrome is a rare autosomal dominant syndrome that is believed to be a variant of hereditary nonpolyposis colorectal cancer ("lynch syndrome"). lynch syndrome is characterized by a high risk of colon cancer along with endometrial, ovarian, stomach, and other cancers, and it is caused by inherited mutations that impair dna mismatch repair. muir-torre syndrome has been identified in 28% of family members and 9% of individuals with lynch syndrome1. however, in comparison to lynch syndrome, specific neoplasms in muir-torre syndrome may lead to the correct diagnosis even when an obvious family history is not present, as diagnosis requires only the presence of at least one sebaceous gland tumor (either an adenoma, epithelioma, or carcinoma) and one or more internal malignancies2. individuals with muir-torre syndrome are prone to numerous keratoacanthomas and sebaceous tumors3, and the most commonly associated malignancies include colorectal (56%), urogenital (22%), small intestine (4%), and breast cancers (4%)4. these colorectal cancers tend to develop 15 to 20 years earlier than normal, with a median age of onset of 50. additionally, one study found that fordyce spots (ectopic sebaceous glands) were found in all patients with confirmed muir-torre syndrome, but only 6.4% of controls5. since many patients with sebaceous neoplasms do not have muir-torre syndrome, the mayo muir-torre risk score was designed to clinically identify patients at greater risk for the syndrome6. a score of 2 or greater indicates a high positive predictive value, while the syndrome is less likely with a score of 1 or fewer. these criteria include early age of onset of first sebaceous neoplasm (younger than 60), increased number of sebaceous neoplasms (2 or more), personal history of lynch-related cancer, and family history of lynch-related cancer. the genes involved in muir-torre syndrome include mlh-1, msh-2, and msh-6, all of which are involved in dna mismatch repair. the loss of mismatch repair proteins leads to microsatellite instability, which results in short, repetitive dna sequences that are susceptible to mutation during dna replication. by staining for the msh-2, mlh-1, msh-6, and pms-2 proteins, sensitivity for detecting loss of expression of mismatch repair proteins approaches 90%7. furthermore, lack of expression of mlh-1 or msh-2 has been associated with microsatellite instability in all reported cases, and mutations in these genes are believed to produce the most profound effects8. for these reasons and due to the infrequency of sebaceous neoplasms, researchers have recommended the use of routine immunohistochemistry for all patients with sebaceous growths9. furthermore, patients with abnormal mismatch repair protein staining and/or microsatellite instability are advised to undergo germline mutational analysis to confirm or rule out the diagnosis. it is suggested that muir-torre syndrome patients be treated with oral isotretinoin, which has been discovered to stall tumor growth10. it is also advised that these patients follow the same screening criteria for colon cancer and other malignancies as those with lynch syndrome. these screening guidelines include that patients with muir-torre syndrome and their first degree relatives undergo annual skin exam for lesions suspicious of sebaceous carcinoma or keratoacanthoma, annual colonoscopy starting at the ages of 20-25, annual screening for endometrial and ovarian cancer, endometrial biopsy and transvaginal ultrasound beginning at 30 35 years, upper endoscopy with biopsy of the gastric antrum beginning at 30-35 years, and annual urinalysis and cytologic discussion skin july 2017 volume i issue i 47 copyright 2017 the national society for cutaneous medicine exam beginning at 30-35 years11. since sebaceous neoplasms can precede, coincide with, or follow internal manifestations of disease, early identification of muir-torre syndrome is valuable to increase detection of any associated malignancies, and it is also useful to provide counseling for family members at risk of premature malignancies. conflict of interest disclosures: none funding: none references: 1. south cd, hampel h, comeas i, et al. the frequency of muir-torre syndrome among lynch syndrome families. oxford journal. 2008; 100(4):277-81. 2. cohen pr, kohn r, kurzrock r. association of sebaceous gland tumors and internal malignancy: the muir–torre syndrome. the american journal of medicine. 1991; 90(5): 606-13. 3. ponti g, ponz de leon m. muir-torre syndrome. lancet oncol. 2005; 6(12):980-7. 4. akhtar s, oza kk, khan sa, wright j. muir-torre syndrome: case report of a patient with concurrent jejunal and ureteral cancer and a review of the literature. j am acad dermatol. 1999; 41(5 pt 1):681–6. 5. ponti g, meschieri a, pollio a, et al. fordyce granules and hyperplastic mucosal sebaceous glands as distinctive stigmata in muir-torre syndrome patients: characterization with reflectance confocal microscopy. j oral pathol med. 2015; 44(7):552-7. 6. roberts me, riegert-johnson dl, thomas bc, et al. a clinical scoring system to identify patients with sebaceous neoplasms at risk for the muir torre variant of lynch syndrome. genet med. 2014; 16(9):711-6. 7. abbas o, mahalingam m. cutaneous sebaceous neoplasms as markers of muir-torre syndrome: a diagnostic algorithm. j cutan pathol. 2009; 36(6):613-9. 8. machin p, catasus l, pons c. microsatellite instability and immunostaining for msh-2 and mlh-1 in cutaneous and internal tumors from patients with the muir-torre syndrome. j cutan pathol. 2002; 29(7):415-20. 9. orta l, klimstra ds, qin j, et al. towards identification of hereditary dna mismatch repair deficiency: sebaceous neoplasm warrants routine immunohistochemical screening regardless of patient's age or other clinical characteristics. am j surg pathol. 2009; 33(6): 934-44. 10. graefe t, wollina u, schulz h, burgdorf w. muir-torre syndrome – treatment with isotretinoin and tnterferon alpha-2a can prevent tumour development. dermatology. 2000; 200(4): 331-3. 11. giardiello fm, allen ji, axilbund je, et al. guidelines on genetic evaluation and management of lynch syndrome: a consensus statement by the us multi-society task force on colorectal cancer. dis colon rectum. 2014; 57(8):1025-4. skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 453 original research the integrated 31-gene expression profile (i31-gep) test for cutaneous melanoma outperforms a clinicopathologic-only nomogram at identifying patients who can forego sentinel lymph node biopsy danny zakria, md, mba1, nicholas brownstone, md2, darrell s. rigel, md, ms3 1 national society for cutaneous medicine, new york, ny 2 department of dermatology, temple health, philadelphia, pa 3 department of dermatology, mount sinai icahn school of medicine, new york, ny abstract introduction: national guidelines for cutaneous melanoma suggest avoiding sentinel lymph node biopsy (slnb) if the risk of sln positivity is <5% (t1a with no high-risk features), considering slnb if the risk is 5-10% (t1a with additional high-risk features (t1ahr) and t1b), and offering slnb if the risk is >10% (t2-t4). because most patients (88%) who undergo an slnb have a negative result, novel tools to identify patients who can safely forgo slnb are critical. the integrated 31-gene expression profile (i31-gep for slnb) test for cutaneous melanoma combines tumor molecular biology with clinicopathologic features to provide a precise risk of sln positivity. the melanoma institute of australia (mia) developed a nomogram that uses only clinicopathologic features to predict sln positivity. methods: we compared the i31-gep for slnb to the mia nomogram in patients with t1-t2 tumors with complete data (n=582). the precision of each tool to identify patients with <5% sln positivity risk was analyzed using 95% confidence intervals. to be considered low risk, the predicted risk must be <5% and the upper 95% confidence interval must be ≤10%, and to be considered high-risk, the predicted risk must be >10% and the lower 95% ci ≥5%. results: the i31-gep for slnb identified 28.5% (166/582) of patients as having a <5% risk of sln positivity while also having an upper 95% ci ≤10% compared with 0.9% (5/582, p<0.001) using the mia nomogram. in patients with a pre-test likelihood of sln positivity of 510% (t1ahr-t1b), the i31-gep reclassified risk in 60.2% (171/284) of patients as being <5% or >10% compared to 13.7% (39/284, p<0.001) using the mia nomogram. in patients with a known sln status (n=466), the i31-gep for slnb identified 22.1% (103/466) of patients as having <5% risk, with a 3.9% (4/103) sln positivity rate compared to 0.6% (3/466, p<0.001) identified by the mia as having a <5% risk with a 33.3% (1/3) sln positivity rate. conclusions: the i31-gep test outperformed the mia nomogram in identifying patients who could safely forego slnb. integrating the 31-gep molecular risk stratification tool with clinicopathologic features provides precise sln positivity risk to better guide patient management in patients with t1-t2 tumors, for whom slnb guidance could be most impactful. skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 454 the national comprehensive cancer network (nccn) has published guidelines for managing cutaneous melanoma (cm),1,2 which base patient management recommendations on american joint committee on cancer (8th edition; ajcc8) staging.1 these guidelines recommend that sentinel lymph node biopsy (slnb) not be performed in patients with <5% risk of having a positive sln (t1a tumors with no high-risk features), that the option for slnb be discussed with patients for consideration in those with 5-10% risk (t1a with at least one high-risk feature (t1ahr), t1b tumors), and offered to patients with >10% risk (t2-t4).1 following these guidelines for performing slnb results in slnb negativity rates of up to 88% (>95% sln negative in thin tumors), suggesting that most patients are receiving slnb unnecessarily.3 in patients with t1b tumors, the positivity rate can drop below 5%,4–6 and while multiple studies suggest patients with t2 tumors have >10% risk of sln positivity,7–9 others report a rate between 5% and 10%,3,10 suggesting that a subgroup of patients with t2 tumors could have a lower slnb risk than currently suggested in guidelines. two potential reasons for a high slnb negativity rate are that slnb recommendations are based on aggregate data from large, broad risk groups rather than considering each patient’s tumor individually, and current guidelines do not integrate the additional prognostic information that the molecular biology of the tumor provides. therefore, tools to identify patients with a low risk of sln positivity could aid in better resource allocation and reduce unnecessary surgeries and potential complications. however, the precision of a model recommendation is also critical for effective management. if a tool estimates the risk of a positive sln as <5% (recommended to forego slnb) for a given patient, but the confidence intervals (cis) associated with the estimate cross the 10% risk threshold (recommended to “discuss and offer” slnb), the patient and clinician cannot be confident that the actual risk of sln positivity is truly <5%. the melanoma institute australia (mia) developed a nomogram to identify patients at low or high risk of a positive sln that uses only clinical and pathological features.11 however, an editorial noted that using the mia nomogram for a 50-year-old patient with a superficial spreading cm with a breslow thickness of 0.5 mm without ulceration, mitoses, or lymphovascular invasion suggests a 5% risk of sln metastasis. however, the 95% cis for the sln positivity prediction for this patient ranged from 0-20%, thus leading to an equivocal recommendation to pursue or forego slnb.12 in addition, limitations in that model have been documented; specifically, there are discordances (upwards of 50%) on certain tumor subtyping and lymphovascular invasion reporting variability, which could affect nomogram risk predictions, particularly for patients with thin tumors.12 therefore, other objective factors could improve the precision of sln metastasis risk prediction, especially in thin tumors for which recommendations guiding slnb are not definitive. the 31-gene expression profile test (31-gep; decisiondx-melanoma, castle biosciences, friendswood, tx) for cutaneous melanoma has been validated across numerous independent prospective and retrospective studies and meta-analyses as an independently significant molecular risk stratification tool to identify patients at high and low risk of recurrence or metastasis.13–18 introduction skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 455 table 1. variables included in the i31-gep for slnb or mia model potential prediction variables included in i31-gep test relative importance* included in mia model relative importance** 31-gep continuous score √ 91.3 p<0.001 breslow thickness (per mm) √ 53.5 p<0.001 √ 1.75 p<0.001 mitotic rate √ (continuous) 20.7 p<0.001 √ (0-4+) 1.89-2.47 p<0.05 for all ulceration (presence) √ 19.1 p<0.001 √ 1.32 p=0.008 age (years) √ 10.5 p=0.001 √ 0.97 p<0.001 lymphovascular invasion (presence) √ 4.31 p<0.001 tumor subtype √ superficial spreading melanoma reference acral melanoma 2.15 p=0.002 pure desmoplastic melanoma 0.06 p=0.007 lentigo maligna melanoma 0.52 p=0.079 nodular melanoma 0.62 p<0.001 tumor-infiltrating lymphocytes microsatellites sex transected bases tumor site regression *log-likelihood value (g2); reported in whitman et al. jco po 2021. **odds ratio; reported in lo et al. jco 2020. skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 456 figure 1. consort diagram figure 2. precision of the i31-gep compared to the mia nomogram. the i31-gep for slnb returns a continuous risk score, while the mia reports risk values as whole integers, resulting in the stepwise appearance in the mia graph. skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 457 moreover, when combined with t-stage and patient age, the 31-gep model identifies a group of patients with <5% risk of sln positivity who have high survival rates and can likely safely forego slnb.19 the 31-gep has been analytically validated, showing high reproducibility and confidence in the obtained result.20 recently, the 31-gep score was integrated with clinical and pathological features using a neural network algorithm to accurately and precisely identify patients with a <5% risk of having a positive sln who may forego slnb (i31-gep for slnb),21 and separately using cox regression to identify patients at low or high risk of recurrence, metastasis, or death from melanoma (i31gep for ror).22 the i31-gep for slnb provides high sensitivity and negative predictive value in patients with t1ahr-t2 melanoma.23 the purpose of this study was to compare the ability of the i31-gep for slnb versus the mia nomogram outputs to predict sln positivity and analyze the precision of the results to assess the ability to appropriately apply the results in the clinical setting in patients with t1ahr-t2 melanomas. we performed a comparison of: 1) the i31gep for slnb, which integrates the 31-gep continuous score with breslow thickness, mitotic rate, ulceration status, and age using a neural network algorithm;21 and 2) the mia nomogram, which utilizes age, tumor thickness, mitotic rate, melanoma subtype, ulceration, and lymphovascular invasion (lvi).11 the relative importance of the factors in each tool are listed in table 1. patients with t1-t4 tumors from a previous validation cohort, for whom all the necessary data to use the i31-gep for slnb and the mia nomogram were available, were included n=913). primary analyses were performed in patients with t1a tumors with at least one high-risk feature (t1ahr), t1b, and t2 tumors (n=582, figure 1).21 high-risk (hr) features included mitotic rate ≥2/mm2, lymphovascular invasion (lvi), absence of tumor-infiltrating lymphocytes, microsatellites, regression, age <40 years, and transected base. the precision of the i31-gep for slnb and mia nomogram was analyzed using 95% cis. patients were considered low risk only if they had <5% risk of sln positivity and had an upper 95% ci ≤10% and were considered high risk only if they had >10% sln positivity risk and a lower 95% ci ≥5%. due to concerns around the diagnosis of pure vs. mixed desmoplastic tumor subtype,12 desmoplastic tumors were not included in the analysis. cis for the mia nomogram were obtained directly from the nomogram output. for the i31-gep for slnb, observed nodal positivity rates and associated 95% cis were derived by a locally estimated scatter smoothing (lowess) spline fitting of the nodal positivity and predicted nodal positivity from the i31-gep for slnb algorithm. patient demographics are shown in table 2. the slnb performance rate was 80.1% (466/582), with an overall 10.5% (49/466) positivity rate. the i31-gep for slnb identified 28.5% (166/582) as having both <5% risk of positivity and an upper 95% ci ≤10% compared to 0.9% (5/582, p<0.001) using the mia nomogram (figure 2). analysis in all t1-t4 tumors (n=913) showed similar results, as illustrated in figure 3. because slnb recommendations are unclear for patients with 5-10% risk (t1ahrt1b, “consider” slnb), we next analyzed this subset of patients (n=284). the i31-gep for methods results skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 458 table 2. patient demographics in t1-t4 (n=913) age (years), median (range) 63 (21-90+) t-stage, % (n) t1a 20.5% (187) t1b 17.3% (158) t2a 25.8% (236) t2b 6.8% (62) t3a 10.1% (92) t3b 9.9% (90) t4a 3.4% (31) t4b 6.2% (57) mitotic rate, 1/mm2, (range) 2 (0-10) lymphovascular invasion, % (n) 3.2% (30) tumor subtype, % (n) superficial spreading 56.3% (514) lentigo maligna 4.6% (42) nodular 37.5% (342) acral 1.6% (15) slnb performance, % (n) 78.4% (716) sln positivity, % (n) 14.9% (107) hr: high-risk feature, including mitotic rate ≥2/mm2 (cap mr at 10/mm2), lymphovascular invasion, absence of tumor-infiltrating lymphocytes, presence of microsatellites, regression, transected base. skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 459 figure 3. precision of the i31-gep to the mia nomogram. the i31-gep for slnb returns a continuous risk score, while the mia reports risk values as whole integers, resulting in the stepwise appearance in the mia graph. skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 460 slnb reclassified risk in 60.2% (171/284) of patients; 49.6% were downgraded to forego slnb (<5% risk; 141/284), and 10.6% were upgraded to offer slnb (>10% risk; 30/284). mia reclassified risk for significantly fewer patients (13.7%; 39/284, p<0.001); risk was downgraded to <5% for 1.4% (4/284) and upgraded to >10% for 12.3% (35/284) of t1 cases (table 3). in patients with t1ahr-t2 tumors with pathologically assessed slns (n=466), the i31-gep for slnb identified 22.1% (103/466) with <5% risk (upper 95% ci ≤10%), with a 3.9% (4/103) sln positivity rate (table 4). the mia identified 0.6% (3/466, p<0.001) patients with <5% risk (upper 95% ci ≤10%), but these had a 33% (1/3) sln positivity rate (table 4). most patients undergoing slnb, particularly in thin tumors, receive a negative result.3 a precise method to identify patients with a low or high risk of sln positivity can aid in the decision to perform an slnb. various tools have been developed to better identify patients with a low risk of sln positivity who can safely forego the procedure, including the i31-gep for slnb and the mia nomogram.11,21 this study demonstrated that the i31-gep for slnb was more precise in identifying patients with <5% risk of sln positivity than the mia. moreover, in the cohort of patients for which slnb guidance is not definitive (t1ahr-t1b; 5-10% risk; “consider” slnb), the i31-gep for slnb reclassified the majority (60%) of patients into definitive risk groups, compared to only 14% using mia. additionally, in those patients with <5% risk calculated by the i31-gep for slnb, the positivity rate was low (3.9%). an important limitation of the mia nomogram is the inclusion of the tumor histologic subtype, for which considerable discordance is documented.24 specifically, 34% of superficial spreading melanoma, 48% of nodular melanoma, and 63% of lentigo maligna melanoma diagnoses were shown to be discordant between community pathologists and dermatopathologists,24 and this discordance could have large effects on the mia risk estimate. for instance, using the mia nomogram to analyze the data for a 65year-old patient with a 1.5-mm superficial spreading melanoma with two mitoses/mm2, no ulceration, and no lymphovascular invasion would result in an sln positivity risk of 11% (95% ci, 9-13%), and the patient should be offered slnb. however, if the tumor subtype was misdiagnosed as lentigo maligna melanoma, the sln positivity risk drops to 6% (95% ci 1-34%), and the recommendation would instead be to “discuss and consider” slnb. a recent study demonstrated that patients with a clinically or pathologically negative sln (i.e., stage i-ii diagnosed before approval of adjuvant therapy in nodenegative patients) have varying 5-year recurrence-free survival (rfs) rates, ranging from 93.3% for stage ia to 57.1% for stage iic.25 a tool that can identify patients who can forego slnb without providing risk of recurrence information does not provide comprehensive patient management utility, as many patients with a negative slnb will still experience recurrence. when considering a melanoma patient’s path from diagnosis through management, slnb represents just one decision point. tools to help guide care after the slnb decision is made, including frequency of clinical visits, necessity and frequency of imaging, and benefits of adjuvant therapy, can help refine patient survival prognosis for better riskaligned management plans. multiple studies have demonstrated that clinicians combine 31-gep results with other factors to align management plans with patient risk.26–28 no discussion skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 461 table 3. reclassification of risk in patients with 5-10% sln positivity risk (“consider” slnb; t1ahr-t1b) for whom slnb guidance is not definitive table 4. a comparison of i31-gep for slnb and mia to correctly identify patients with a low risk of sln positivity in patients with t1ahr-t2 sln-assessed tumors test nccn risk reclassified as <5%, % (n/n) reclassified as >10%, % (n/n) combined reclassified, % (n/n) p-value i31gep 5-10% (t1ahr-t1b) n=284 49.6% (141/284) 10.6% (30/284) 60.2% (171/284) <0.001 mia 1.4% (4/284) 12.3% (35/284) 13.7% (39/284) because this analysis does not look at sln positivity, it includes sln-assessed and unassessed patients; therefore, the analyzable cohort is larger than shown in table 3. patients were included in the <5% risk group if the risk estimate was <5% and the upper 95% ci was also ≤10%. patients were included in the >10% risk group if risk estimate was >10% and the lower 95% ci was also ≥5%. test <5% risk sln positivity >10% risk sln positivity 510% risk sln positivity total sln positivity slnb reduction rate pvalue i31gep for slnb 103 3.9% (4/103) 148 15.5% (23/148) 215 10.2% (22/215) 10.5% (49/466) 22.1% (103/466)* <0.001 mia 3 33.3% (1/3) 125 14.4% (18/125) 338 8.9% (30/338) 0.6% (3/466)* patients in the <5% risk group had an upper 95% ci ≤10% and patients in the >10% risk group had a lower 95% ci ≥5%. t1ahrt2 tumors. * indicates a significant difference (p<0.001) between i31-gep for slnb and the mia nomogram. skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 462 studies to date have demonstrated the clinical utility of the mia nomogram. limitations of this study include its retrospective nature and that this selected population from primarily surgical centers may not represent the general population. in addition, comparison to the mia nomogram limited patient inclusion, primarily due to missing subtypes, in more than 50% of cases. despite these limitations, this study provides evidence that the i31-gep for slnb can guide risk-aligned slnb decisions.22,26,27 decisions regarding patient care are made in multi-disciplinary settings, and tools such as the i31-gep for slnb supplement traditional clinical and pathologic factors and offer independent, objective risk prediction to aid clinicians in determining the best treatment plan for individual patients. however, clinicians need confidence that a tool will provide precise prognostic information. this study demonstrated that the i31-gep for slnb outperforms the mia nomogram for selecting patients for slnb, given the more precise result provided, and using the i31gep for slnb could lead to a more accurate assignment of the patient into the appropriate nccn sln risk grouping. the findings of this study suggest that integrating the 31-gep with clinicopathologic features can improve patient care through better risk-aligned management decisions for slnbs and reduce the number of unnecessary slnbs. conflict of interest disclosures: dsr is a consultant, investigator, and speaker for castle biosciences, inc. (cbi) funding: materials and funding for this study were provided by cbi corresponding author: danny zakria, md, mba 234 e 85th st. new york, ny email: dzakria13@gmail.com references: 1. national comprehensive cancer network. melanoma: cutaneous, version 2.2021 february 19, 2021, in nccn clinical practice guidelines in oncology (nccn guidelines). nccn https://www.nccn.org/guidelines/category_1 (2021). 2. gershenwald, j. e. et al. melanoma staging: evidence-based changes in the american joint committee on cancer eighth edition cancer staging manual. ca: a cancer journal for clinicians 67, 472–492 (2017). 3. chen, j. et al. prognostic role of sentinel lymph node biopsy for patients with cutaneous melanoma: a retrospective study of surveillance, epidemiology, and end-result population-based data. oncotarget 7, 45671– 45677 (2016). 4. friedman, c., lyon, m., torphy, r. j., thieu, d. & hosokawa, p. a nomogram to predict node positivity in patients with thin melanomas helps inform shared patient decision making. journal of surgical oncology 1276–1283 (2019) doi:10.1002/jso.25720. 5. weitemeyer, m. b., helvind, n. m., brinck, a. m., hölmich, l. r. & chakera, a. h. more sentinel lymph node biopsies for thin melanomas after transition to ajcc 8th edition do not increase positivity rate: a danish population‐based study of 7148 patients. j surg oncol jso.26723 (2021) doi:10.1002/jso.26723. 6. egger, m. e. et al. should sentinel lymph node biopsy be performed for all t1b melanomas in the new 8th edition american joint committee on cancer staging system? journal of the american college of surgeons 228, 466–472 (2019). 7. teixeira, v. et al. prediction of sentinel node status and clinical outcome in a melanoma centre. journal of skin cancer 2013, 1–7 (2013). 8. sondak, v. k. et al. mitotic rate and younger age are predictors of sentinel lymph node positivity: lessons learned from the generation of a probabilistic model. ann surg oncol 11, 247–258 (2004). 9. paek, s. c. et al. the impact of factors beyond breslow depth on predicting sentinel conclusion skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 463 lymph node positivity in melanoma. cancer 109, 100–108 (2007). 10. cascinelli, n. et al. sentinel and nonsentinel node status in stage ib and ii melanoma patients: two-step prognostic indicators of survival. jco 24, 4464–4471 (2006). 11. lo, s. n. et al. improved risk prediction calculator for sentinel node positivity in patients with melanoma: the melanoma institute australia nomogram. jco jco.19.02362 (2020) doi:10.1200/jco.19.02362. 12. faries, m. b. improved tool for predicting sentinel lymph node metastases in melanoma. jco 38, 2706–2708 (2020). 13. arnot, s. p. et al. utility of a 31-gene expression profile for predicting outcomes in patients with primary cutaneous melanoma referred for sentinel node biopsy. am j surg 221, 1195–1199 (2021). 14. hsueh, e. c. et al. long-term outcomes in a multicenter, prospective cohort evaluating the prognostic 31-gene expression profile for cutaneous melanoma. jco precision oncology 5, 589–601 (2021). 15. jarell, a. et al. the 31-gene expression profile stratifies recurrence and metastasis risk in patients with cutaneous melanoma. future oncology fon-2021-0996 (2021) doi:10.2217/fon-2021-0996. 16. keller, j. et al. prospective validation of the prognostic 31‐gene expression profiling test in primary cutaneous melanoma. cancer med 8, 2205–2212 (2019). 17. zager, j. s. et al. performance of a prognostic 31-gene expression profile in an independent cohort of 523 cutaneous melanoma patients. bmc cancer 18, 130 (2018). 18. greenhaw, b. n. et al. molecular risk prediction in cutaneous melanoma: a metaanalysis of the 31-gene expression profile prognostic test in 1,479 patients. journal of the american academy of dermatology 83, 745–753 (2020). 19. vetto, j. t. et al. guidance of sentinel lymph node biopsy decisions in patients with t1–t2 melanoma using gene expression profiling. future oncology 15, 1207–1217 (2019). 20. cook, r. w. et al. analytic validity of decisiondx-melanoma, a gene expression profile test for determining metastatic risk in melanoma patients. diagn pathol 13, 13 (2018). 21. whitman, e. d. et al. integrating 31-gene expression profiling with clinicopathologic features to optimize cutaneous melanoma sentinel lymph node metastasis prediction. jco precision oncology 1466–1479 (2021) doi:10.1200/po.21.00162. 22. jarell, a. et al. optimizing treatment approaches for patients with cutaneous melanoma by integrating clinical and pathologic features with the 31-gene expression profile test. journal of the american academy of dermatology s0190962222022538 (2022) doi:10.1016/j.jaad.2022.06.1202. 23. marchetti, m. a., dusza, s. w. & bartlett, e. k. utility of a model for predicting the risk of sentinel lymph node metastasis in patients with cutaneous melanoma. jama dermatology (2022) doi:10.1001/jamadermatol.2022.0970. 24. yardman-frank, j. m. et al. comparison of community pathologists with expert dermatopathologists evaluating breslow thickness and histopathologic subtype in a large international population-based study of melanoma. jaad international 4, 25–27 (2021). 25. garbe, c. et al. prognosis of patients with primary melanoma stage i and ii according to american joint committee on cancer version 8 validated in two independent cohorts: implications for adjuvant treatment. journal of clinical oncology (2022) doi:10.1200/jco.22.00202. 26. berger, a. c. et al. clinical impact of a 31gene expression profile test for cutaneous melanoma in 156 prospectively and consecutively tested patients. curr med res opin 32, 1599–1604 (2016). 27. dillon, l. d. et al. expanded evidence that the 31-gene expression profile test provides clinical utility for melanoma management in a multicenter study. curr med res opin 1–21 (2022) doi:10.1080/03007995.2022.2033560. 28. scott, a. m., dale, p. s., conforti, a. & gibbs, j. n. integration of a 31-gene expression profile into clinical decisionmaking in the treatment of cutaneous melanoma. am surg 86, 1561–1564 (2020). skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 351 skimages an unusual clinical presentation of cutaneous syphilis tue felix nguyen, bs1, anaya shah, bs1, bahar momin, bba1, marie vu, bsa1, john browning, md2 1ut health san antonio, long school of medicine, san antonio, tx 2department of dermatology, ut health san antonio, san antonio, tx figure 1: annular, friable violaceous plaque with surrounding erythematous raised border with solitary nodules containing pinpoint petechiae a 33-year-old black homosexual male presented with a plaque that appeared four months after he injured his hand on a metal railing under his car seat. a 3.0 x 3.5 cm well-defined, annular friable violaceous plaque with surrounding erythematous raised border with solitary nodules containing pinpoint petechiae was seen on physical examination (figure 1). his medical history was significant for hiv, and he admitted to stopping his antiretroviral treatment two months prior to presentation. similar appearing lesions were present on his back and scrotum. the initial differential diagnosis included a deep fungal infection, granuloma annulare, kaposi's sarcoma, and neutrophilic dermatosis of skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 352 the hands. minocycline 100 mg twice daily for 14 days was prescribed, with notable improvement at the two-week follow-up. histopathology showed psoriasiform epidermal hyperplasia with elongated thin rete ridges and a superficial to mid dermal perivascular and periadnexal infiltrate of lymphocytes, histiocytes, some neutrophils, and numerous plasma cells. the infiltrate obscured the dermo-epidermal junction, which was associated with vacuolar alteration and necrotic keratinocytes. spirochete immunohistochemistry was done and yielded the presence of rare spirochetes within the specimen (figure 2). the diagnosis of syphilis was made, and the health department was contacted for further treatment. figure 2: positive spirochete immunohistochemistry stain in biopsy specimen syphilis is a sexually transmitted infection (sti) caused by the bacteria treponema pallidum that presents with symptomatic and asymptomatic stages. the incidence of syphilis has been increasing since the early 2000s, when the rates of syphilis were at their historic lowest. between 2019 to 2020, the rate of syphilis increased by 6.8%. men especially are vulnerable, as many cases are seen in men who have sex with men.1 co-infection with syphilis and hiv is highest in african americans, which may alter the clinical presentations of either disease.2 syphilis is known as the “great mimicker,” both clinically and histologically; it can present differently depending on the stage of the infection and when the biopsy was taken. diagnosis of syphilis is made by a screening rapid plasma reagin test (rpr) followed by a more specific fluorescent treponemal antibody test absorption test (fta-abs). cutaneous manifestations of syphilis are often atypical and even more variable within skin of color (soc) patients, further complicating the diagnostic process. reports of papulosquamous syphilis have presented in an ichthyosiform photo-distributed pattern within black populations.3 similarly, syphilitic alopecia in caucasian and soc patients may often mimic alopecia areata with its “moth-eaten,” non-scarring distribution.4 due to the variance of syphilis and how it can resemble other conditions, misdiagnosis without additional testing can delay treatment and worsen disease progression. our case highlights an unusual presentation of cutaneous syphilis in a vulnerable population and how a diagnosis is difficult based on clinical presentation alone. serologic testing or a biopsy is necessary to make a proper diagnosis. while intramuscular 2.4 million units benzathine penicillin g single dose remains the gold standard of treatment, minocycline has been shown to be an effective alternative therapy for early syphilis if penicillin is unavailable.5 skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 353 conflict of interest disclosures: none funding: none corresponding author: tue felix nguyen, bs ut health san antonio long school of medicine san antonio, tx 78229 email: nguyent47@livemail.uthscsa.edu references: 1. national overview of stds, 2020. center for disease control and prevention. https://www.cdc.gov/std/statistics/2020/overvi ew.htm#syphilis. accessed may 26, 2022. 2. funnyé as, akhtar aj. syphilis and human immunodeficiency virus co-infection. j natl med assoc. 2003;95(5):363-382. 3. ivars lleó m, clavo escribano p, menéndez prieto b. atypical cutaneous manifestations in syphilis. manifestaciones cutáneas atipícas en la sífilis. actas dermosifiliogr. 2016;107(4):275-283. doi:10.1016/j.ad.2015.11.002 4. doche i, hordinsky mk, valente nys, romiti r, tosti a. syphilitic alopecia: case reports and trichoscopic findings. skin appendage disord. 2017;3(4):222-224. doi:10.1159/000477415 5. shao ll, guo r, shi wj, et al. could lengthening minocycline therapy better treat early syphilis?. medicine (baltimore). 2016;95(52):e5773. doi:10.1097/md.0000000000005773 powerpoint presentation performance and clinical decision-making using the prognostic 40-gene expression profile (40-gep) test in 1,018 patients with high-risk cutaneous squamous cell carcinoma (scc) jennifer j. siegel, phd1; anesh prasai, phd1; aaron s. farberg, md2; matthew s. goldberg, md1,3 1castle biosciences, inc. friendswood, tx; 2baylor scott & white health system, dallas, tx; 3icahn school of medicine at mount sinai, new york, ny background › the 40-gene expression profile (40-gep) test categorizes patients with a primary scc who have one or more clinicopathologic risk factors into three biological risk groups based on the likelihood of regional, nodal, or distant metastasis (low= class 1; moderate= class 2a; high= class 2b).6 › the 40-gep test has been shown to improve risk assessment and provide more precise, individualized metastatic risk stratification when combined with current risk prediction methods.6,7 › clinical utility studies have demonstrated the ability of 40-gep test results to guide risk-aligned patient management including changes to follow-up, surveillance imaging, slnb, and art following 40-gep testing ( table 1).8-10 this study was sponsored by castle biosciences, inc. (cbi), which provided funding to the contributing centers for tissue and clinical data retrieval. jjs, ap, and msg are employees and options holders of cbi. asf is a consultant for cbi. 40-gep risk class overall cohort 3-year mfs (95% ci) overall event rate univariate cox regression analysis (hr) class 1 95.3% (93.6-97.0%) 5.1% 1 class 2a 81.9% (78.2-85.8%) 18.8% 4.0 class 2b 56.9% (44.8-72.2%) 43.1% 11.4 without 40-gep 88.2% (86.3-90.2%) 12.3% -methods references 1. rogers, jama derm 2015 2. karia, jaad 2013 3. cañueto, jaad 2019 4. ruiz, jama derm 2019 5. nccn guidelines v2.2022 6. wysong, jaad 2021 7. ibrahim, future onc 2021 8. hooper, cancer inv 2022 9. teplitz, jdd 2019 › the two independent cohorts (n=420, validation7 n=598, performance11) were compared and then combined (n=1,018). › overall event (i.e., metastasis) rates, kaplan-meier analysis for metastasis-free survival, and univariate cox regression analysis were performed for both the individual and combined cohorts. › clinical utility and management changes in the combined cohort were modeled based on the preand post-40-gep test results of a published clinical impact study of real-world cases.8 results n=1,018 p<0.0001m e ta s ta s is -f re e s u rv iv a l 100% 80% 0% 20% 40% 60% years 0 2 3 4 51 class 1 class 2a class 2b ibrahim et al.7 (n=420) overall event rate = 15.0% arron et al.11 (n=598) overall event rate = 9.9% relative fold change (class/overall) relative fold change (class/overall) class 1 0.4x 0.4x class 2a 1.3x 1.7x class 2b 3.5x 3.6x table 2. 40-gep accurately and consistently stratifies metastatic risk presented at fall clinical dermatology conference, october 20-23, 2022, las vegas nv for more information: jsiegel@castlebiosciences.com 10. litchman, future onc 2021 11. arron, presented at acms 2022 › in two independent high-risk scc cohorts, the 40-gep consistently demonstrates significant metastatic risk stratification. › when cohorts are combined, the 40-gep continues significant performance in identifying metastatic risk, as shown with patients receiving class 2a and class 2b results incurring a 4and 11-fold increase in metastasis, respectively, when compared to those with class 1 results. › the impact of the 40-gep on management decisions modeled across this large cohort represents a substantial improvement in risk-aligned clinical decision-making. conclusions disclosures figure 1. performance of the 40-gep to stratify high-risk scc patients by risk for regional or distant metastasis (n=1,018) p < 0.0001; ci= confidence interval; hr= hazard ratio; mfs= metastasis free survival figure 2. 60% of patients in the combined cohort would have a risk-aligned change in management plans post-40-gep results clinical issue and objective scc is a common skin cancer with overall favorable prognosis. however, due to its high incidence, mortality exceeds that of melanoma.1,2 broad guidelines, along with lack of standardized and accurate risk assessment methods complicates treatment planning for scc patients.3-5 this study reports on 40-gep performance metrics in risk stratification of >1,000 patients and highlight its impact on guiding risk-aligned decisions for patients with scc › when management changes from hooper et al.8 were used on the combined cohort to model clinical utility of the 40-gep, results showed that 60% of high-risk scc patients would have risk-aligned (i.e., escalation of treatment due to class 2a or 2b results; de-escalation due to a class 1 result) alterations in at least one of the following modalities: follow-up frequency, adjuvant radiation therapy, nodal imaging, and surveillance imaging. › kaplan-meier survival analysis of the combined cohort (n=1,018) demonstrated statistically significant 3-year metastasis-free survival between all classes. cox regression analysis established hazard ratios for class 2a and class 2b as 4.0 and 11.4, respectively (p<0.0001). › statistically significant 40-gep-based risk stratification was observed in each of the two independent cohorts (p<0.001, logrank). r is k -a li g n e d c h a n g e i n t re a tm e n t p la n escalation due to class 2a or 2b de-escalation due to class 1 % patients with change due to 40-gep follow-up frequency adjuvant radiation therapy nodal imaging surveillance imaging overall management change 36% 37% 57% 39% 57% table 1. individualized risk-aligned changes in overall management plans are made post-40-gep testing clinical impact studies of 40-gep8-10 clinicians patients specific clinical recommendation changed with 40-gep overall change in management plan recommended with 40-gep 34 real-world test users 6 real-world cases f/u, slnb, baseline nodal imaging, adjuvant radiation (art), adjuvant chemotherapy, surveillance imaging integration of the 40-gep class call significantly impacted recommended patient management plans in a riskappropriate manner while staying within guidelines. 162 dermatologists* 2 patient vignettes f/u, slnb, nodal imaging, adjuvant radiation, adjuvant chemotherapy 402 dermatologists 3 patient vignettes f/u, slnb referral, radiation, chemotherapy, immunotherapy f/u = follow up schedule; slnb = sentinel lymph node biopsy; *majority dermatologists with 8.6% dermatology np/pa, 1.2% dermatopathologist, 1.9% other ozenoxacin p3 pooled_2017 fall clinical.pdf ozenoxacin, a novel, topical antibacterial agent for treatment of adult and pediatric patients with impetigo: phase iii clinical trials pooled analysis results nuria albareda bs1, noah rosenberg md2, sandra roth pharmd2, ilonka zsolt, md phd1, theodore rosen md3, adelaide a. hebert md4 1ferrer internacional sa, barcelona, spain, 2medimetriks pharmaceuticals inc., fairfield, nj, usa, 3baylor college of medicine, houston, tx, usa, 4 uthealth mcgovern medical school, houston, tx usa background: ozenoxacin is a novel topical antibacterial agent with potent bactericidal activity against gram-positive bacteria that has been developed as a 1% cream for treatment of impetigo. this dataset represents a pooled analysis of the two pivotal clinical trials of ozenoxacin. objectives: to evaluate the efficacy, safety, and tolerability of ozenoxacin 1% cream after twice-daily topical treatment for 5 days in patients with impetigo. methods: data from two multicenter, randomized, double-blind, vehicle-controlled studies in patients with impetigo and results were pooled and analyzed. 877 subjects were enrolled in 53 centers in 7 countries (usa, south africa, germany, romania, russia, ukraine, and spain). for both studies patients were deemed eligible if they had a clinical diagnosis of impetigo with a total affected area at baseline not exceeding 100 cm2. for patients <12 years old, the total area could not exceed 2% of the body surface area (bsa). eligible subjects were randomized to receive ozenoxacin 1% cream, placebo cream or retapamulin 1% ointment (study 1 only). in both studies the severity of impetigo at baseline was assessed using the skin infection rating scale (sirs). during the 5-day treatment period, patients were instructed to apply a thin layer of study drug to the baseline affected area(s) twice daily. assessments were conducted at four visits: pre-therapy (baseline, visit 1), on therapy (visit 2, day 3-4), end of therapy (visit 3, day 6-7), and post-therapy (visit 4, day 10-13). in addition, a telephone call was arranged 24 to 36 hours after the start of study medication for early evaluation of whether the patient’s lesions were progressing. efficacy was measured using sirs and microbiological culture. safety and tolerability were evaluated. primary efficacy endpoint: • clinical response (clinical success or clinical failure) at end of therapy (visit 3) in the intent-to-treat clinical (ittc) population. key secondary efficacy endpoints: • clinical response at visit 3 incorporating combined criteria of clinical success (reflecting previously accepted methodology for other topical antibiotics approved for impetigo) and microbiological response at visits 2 and 3. evaluation of safety was based on adverse events, vital signs and physical examination. clinical success was defined as total absence of treated lesions (sirs score 0 for blistering, exudates/pus, crusting, itching/pain, and no more than 1 for erythema/inflammation), such that no additional antimicrobial therapy of the baseline affected area(s) was necessary. improvement (defined as >10% decrease in total sirs score compared with baseline, not fulfilling the criteria of individual sirs scores for cure), as well as failure, were both considered clinical failure. the clinical success rate in the ittc population at the end of therapy (day 6-7, visit 3) for the pooled analysis was 47.3% in the ozenoxacin 1% cream group and 31.4% in the placebo cream group. the statistically significant difference in success rates (15.9%; p<0.001;95%ci=8.9–23.1) confirmed the significantly greater clinical success for ozenoxacin relative to placebo at the end of therapy. • in a pooled analysis of two phase iii studies, ozenoxacin demonstrated a superior clinical and microbiological response compared to vehicle after 5 days of therapy. • ozenoxacin produced more rapid microbiological clearance than placebo after 2 days of therapy. • the rapid clinical response of ozenoxacin could be clinically beneficial in terms of reducing the likelihood of disease spread to other parts of the body or to other persons; this is particularly important in the pediatric population. • data from this pooled analysis demonstrate that ozenoxacin has the potential to be a rapid and effective new treatment for impetigo. combined criteria of clinical response was defined as clinical success or improvement. this broader measure reflects the same criteria for clinical success used in pivotal phase iii clinical trials of other previously approved topical antibiotics for impetigo and includes ‘improvement’ in the definition of clinical success. the difference in success rates (11.5%) was significant (p<0.001; 95% ci=6–17.0). there was evidence that ozenoxacin produced more rapid microbiological clearance than retapamulin after two days of therapy, as highlighted by success rates of 74.7% for ozenoxacin versus 60% for retapamulin (p=0.0087) in study 1 (gropper 2014). clinical results introduction conclusions ozenoxacin vs. retapamulin 2017 fall clinical dermatology conference ® october 12-15, 2017. wynn hotel, las vegas, nevada this poster was funded by: ferrer internacional, sa. and medimetriks pharmaceuticals, inc. key secondary efficacy endpoint: 88.5 77.1 84.2 0 20 40 60 80 100 ozenoxacin 1% cream placebo cream retapamulin ointment pa tie nt s w ith c lin ic al r es po ns e (% ) clinical response at visit 3 with combined criteria of clinical success microbiological results 80.4 90.8 52.3 69.8 0 20 40 60 80 100 visit 2 visit 3 (end of therapy) n (% ) microbiological response at visit 2 and visit 3 (end of therapy) ozenoxacin 1% cream placebo cream microbiological success was defined as eradication, a composite of documented eradication (absence of the original pathogen from the post-treatment culture of the specimen obtained from the original site of infection) and presumed eradication (complete resolution of signs and symptoms associated with absence of culturable material). the differences in the success rates between ozenoxacin 1% cream and placebo cream at visit 2 (28%) and visit 3 (21%) were significant (p< 0.0001). * * * p < 0.0001 demographics and baseline characteristics in the ittc population ozenoxacin 1% cream (n = 361) placebo cream (n = 362) retapamulin 1% ointment (n = 154) overall (n = 877) mean (sd) age (years) 17.6 (18.0) 17.9 (18.0) 15.1 (15.0) 17.3 (17.5) ≥ 2 months to < 12 years old 207 (57.3) 207 (57.2) 95 (61.7) 509 (58.0) ≥ 12 years to < 18 years old 43 (11.9) 40 (11.0) 15 (9.7) 98 (11.2) ≥ 18 years 111 (30.7) 115 (31.8) 44 (28.6) 270 (30.8) male gender, n (%) 211 (58.4) 194 (53.6) 92 (59.7) 497 (56.7) caucasian 180 (49.9) 202 (55.8) 50 (32.5) 432 (49.3) black or african-american 130 (36.0) 115 (31.8) 79 (51.3) 324 (36.9) * p < 0.0001 primary efficacy endpoint: skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 645 skinmages cutaneous involvement of angioimmunoblastic t-cell lymphoma nishad sathe, md1, andrea bershow, md2 1departments of dermatology and medicine, university of minnesota, minneapolis, mn 2chief of dermatology, va medical center, minneapolis, mn figure 1. (a) red-violaceous nodule on the left palmar fifth digit; (b) dermoscopy of nodule *clinical and dermoscopic evidence of scale and erosion, a common finding of cutaneous lymphomas **orange-tan pigmentation and white areas with loss of normal acral ridges ***irregular vessels a 74-year-old man with chronic lymphocytic leukemia and angioimmunoblastic t-cell lymphoma (aitl) of the right lung was undergoing evaluation for initiation of chemotherapy. bendamustine and rituximab were previously initiated but stopped after one month due to adverse effects. the patient subsequently completed 7 years of ibrutinib therapy, which was halted 3 weeks prior to presentation due to its ineffectiveness and significant hematologic lab abnormalities. treatment with chop (cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, prednisone) was proposed, however the patient had a nodule concerning for cellulitis on the left fifth palmar digit requiring treatment prior to chemotherapy initiation. no skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 646 improvement was seen after courses of cephalexin and doxycycline. due to a lack of response to these two antibiotics, dermatology was consulted for further evaluation. on physical exam, there was a 1.3-cm redviolaceous crusted nodule on the palmar aspect of the left fifth digit (figure 1, panel a). dermoscopy showed central orange-tan pigmentation with loss of normal acral ridge pattern and surrounding irregular vessels (figure 1, panel b). the differential diagnosis included sweet syndrome, drug eruption, infection, and malignancy. a punch biopsy was performed and showed an atypical lymphocytic nodular infiltrate with angioinvasive and angiodestructive features, and immunohistochemical stains suggested aitl. the patient’s clinical stage was changed from stage ii to stage iv aitl due to skin involvement, and the patient was started on chop treatment. aitl is a peripheral cd4+ follicular t-helper cell-based lymphoma that presents with b symptoms and generally has a poor prognosis after conventional chemotherapies.1 though rare, aitl has been reported to present with skin manifestations in up to 50% of cases, which typically present as macular or papular eruptions on the trunk, similar to toxic erythema of chemotherapy, drug eruptions, or viral exanthems.2 however, there are multiple case reports of aitl mimicking a variety of systemic dermatologic or oncologic entities, including dermatomyositis, systemic lupus erythematosus, vasculitis, and urticaria.3 this case of aitl with cutaneous involvement illustrates an uncommon presentation of this peripheral lymphoma that often has skin manifestations. the presence of skin involvement implies an advanced clinical stage, which confers a poorer prognosis.4 due to its variable presentations in the skin, it is often misdiagnosed as a vasculitis or exanthem, particularly when its initial presentation is in the skin without prior diagnosis of internal aitl malignancy.3 as in this case, most patients are treated for their condition with chemotherapy, starting with anthracycline-based chemotherapy, and often require higher-dose or modified therapy due to the short response duration.4 here, we highlight the diagnostic challenge of aitl and the clinical importance of its identification for appropriate staging and treatment of this condition. conflict of interest disclosures: none funding: none corresponding author: nishad sathe, md university of minnesota department of dermatology phone: (714) 606-0911 email: nishadcsathe@gmail.com references: 1. tokunaga t, shimada k, yamamoto k, et al. retrospective analysis of prognostic factors for angioimmunoblastic t-cell lymphoma: a multicenter cooperative study in japan. blood. 2012;119(12):2837-2843. 2. papadavid e, panayiotides i, dalamaga m, katoulis a, economopoulos t, stavrianeas n. cutaneous involvement in angioimmunoblastic tcell lymphoma. indian j dermatol. 2010;55(3):279-280. 3. hoskins s, moriarty n, white k, kalus a, shustov a, shinohara mm. cutaneous manifestations of angioimmunoblastic t-cell lymphoma. dermatol online j. 2019;25(7):13030/qt8nt8r6k4. published 2019 jul 15. 4. park bb, ryoo by, lee jh, et al. clinical features and treatment outcomes of angioimmunoblastic t-cell lymphoma. leuk lymphoma. 2007;48(4):716-722. mailto:nishadcsathe@gmail.com skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 272 dermatologic history the legacy of lucio and latapí: a brief history brenda carrillo, bs1 1university of texas medical branch school of medicine, galveston, tx rafael lucio nájera and fernando latapí contributed greatly to the knowledge about a specific form of diffuse lepromatous leprosy, now known as lucio-latapí leprosy. this condition is characterized by generalized, diffuse infiltration without nodules, alopecia of the eyebrows, eyelashes, and body, and anhidrosis and dysesthesias.1 it can also have a reactional state known as lucio’s phenomenon, which presents with necrotic erythema and ulceration of vessels.1 lucio, a mexican physician, published work describing this type of leprosy in 1851.1 however, this condition was mostly isolated to mexico and costa rica.1 for this reason, it garnered little attention until it was brought to light again by latapí in 1936.1 lucio graduated from the establishment of medical sciences in mexico city. 2 he was the director of san lazaro hospital where he extensively researched leprosy.2 he and dr. ignacio alvarado published work describing different types of leprosy, including luciolatapí leprosy. this publication provided clinical descriptions and insights into pathogenesis, therapeutic concepts, and epidemiology that are relevant to date and that served as a foundation for other scholars.3 latapí founded the mexican society of dermatology and the mexican school of leprology.2 the latter aimed to change laws against people with leprosy and promote respectful treatment towards them.2 he worked to abolish misconceptions about leprosy, and created brigades to diagnose thousands of patients.2 at the mexican association of action against leprosy, he successfully treated many patients in a time when leprosy was thought to be incurable.2 this center became the ladislao de la pascua dermatological center, which continues to teach mexican dermatologists today.2 these physicians are pioneers in the field of lepromatous disease. their work also reminds us of the physician’s role in educating and advocating for our patients. figure 1. rafael lucio nájera (left) and fernando latapí (right)2 https://www.zotero.org/google-docs/?2qn036 https://www.zotero.org/google-docs/?2qn036 skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 273 conflict of interest disclosures: none funding: none corresponding author: brenda carrillo, bs university of texas medical branch department of dermatology 301 university blvd. 4.112, mccullough building galveston, tx, usa 77550 email: brecarri@utmb.edu references: 1. al aboud k, al aboud a. eponyms in the dermatology literature linked to latin america. our dermatol online. 2013;3(suppl.1):405-408. doi:10.7241/ourd.20133.102 2. brzeziński p, chiriac a, arenas r, et al. dermatology eponyms – sign –lexicon (l). our dermatol online. 2014;5(2):217-230. doi:10.7241/ourd.20142.58 3. murillo-godínez g. rafael lucio nájera (18191886). med int méx. 2018 septiembreoctubre;34(5):771-779. doi: https://doi.org/10.24245/mim. v34i5.2197 https://www.zotero.org/google-docs/?iihcpu https://www.zotero.org/google-docs/?iihcpu https://www.zotero.org/google-docs/?iihcpu https://www.zotero.org/google-docs/?iihcpu https://www.zotero.org/google-docs/?iihcpu an open-label exploratory study evaluating the efficacy and safety of ingenol mebutate gel 0.05% for the treatment of verruca vulgaris neal d. bhatia, md director, clinical dermatology, therapeutics clinical research, san diego, ca introduction • verruca vulgaris is caused by the human papillomavirus (hpv) and is most frequently associated with hpv types 1, 2, 4, 27, 29, and 57.1,2 it commonly occurs on the hands1,2 • current therapies are aimed at destroying tissue or influencing the body’s inflammatory response against the virus.1 there is no fda-approved topical therapy for common warts2 • ingenol mebutate gel 0.05% is fda approved for the topical treatment of actinic keratosis (ak)3,4 and has a dual mechanism of action: (1) induction of rapid lesion necrosis followed by (2) an inflammatory reaction thought to be mediated by protein kinase c activation5 • hpv-infected keratinocytes behave similarly to keratinocytes damaged by uv in the pathogenesis of ak. these similarities include hyperproliferation and mutagenesis1,2,6; therefore, cytotoxicity of target tissue using an ak topical treatment might be beneficial in wart destruction • a recent case study showed the efficacy of ingenol mebutate against anogenital warts7 • the current study was an open-label, exploratory study using ingenol mebutate gel 0.05% for the treatment of verruca vulgaris on the hands methods design • open-label, exploratory study (figure 1) • conducted at a single site in the us in 2016-2017 • 16 eligible subjects were treated once daily for 2 consecutive days, on days 1 and 2 of the study, with ingenol mebutate gel 0.05% • warts were pared to allow for effective penetration without the callous − additionally, one wart in each subject was occluded with a standard adhesive bandage for 24 hours after each application • follow-up visits occurred on days 8, 29, and 57 to assess application-site reactions (asrs) • at day 57 (study end), wart clearance was assessed figure 1. study design –45 0 8 15 22 29 days 57 screening period treatment period follow-up* *follow-up consisted of major safety assessments, including visual assessment of asrs on a 5-point scale (0=clear to 4=severe) and the recording of adverse reactions. photographs were taken at follow-up visits. at day 57 (study end), patient satisfaction was assessed with a 6-question survey. key inclusion criteria • eligible subjects were >18 years of age; nonpregnant • minimum of 2 and maximum of 5 verrucous papules diagnosed as common warts on the hands, excluding proximity to the nails key exclusion criteria • pregnancy • use of any investigational drug or device that could affect common wart treatment − use of an investigational drug or investigational device treatment within 30 days prior to visit 1 − prior exposure to ingenol mebutate gel physician’s assessments • pregnancy test (day 1) • lesion counts and measurement of wart size (day 1 and 57) • photography (days 1, 2, 8, 29, 57) safety • visual assessment of asrs on a 5-point scale (0=clear to 4=severe) (days 1, 2, 8, 29, 57) • adverse events were recorded questionnaire • 6-question survey on patient satisfaction (at study end, day 57) primary efficacy end point • complete clearance of all warts results • baseline subject demographics and characteristics are described in table 1 table 1. baseline subject demographics and characteristics characteristic age, mean, years 41.17 gender, female, n (%) 6 (37.5) race, n (%) white 14 (87.5) asian 1 (6) other* 1 (6) number of warts at baseline mean 3.38 2 5 subjects ≥3 and ≤5 11 subjects size of warts, mm2 (mean) 0.3 *native hawaiian/pacific islander. treatment regimen • subjects were treated from april 2016 to january 2017 • treatment began after subjects met key inclusion criteria of confirmed common warts • of the identified 54 warts, 16 lesions were occluded and 38 lesions were not occluded − ingenol mebutate gel 0.05% was applied to cover the lesion, plus a 0.5-cm margin − duration of treatment: once daily for 2 consecutive days, on days 1 and 2 of the study � a maximum of one treatment kit (containing 2 tubes of medication) was used primary efficacy end point • the primary end point of complete clearance of all warts was not met in any of the 16 subjects • however, overall wart count was reduced from 54 at baseline to 40 at study end, a 26% reduction in wart count (figure 2a) warts reduced in size • of the non-occluded warts, 57% (22/38) showed a partial reduction in size; they were reduced by 42% in size (figure 2b) • of the occluded warts, 50% (8/16) showed a partial reduction in size; they were reduced by 45% in size (figure 2b) figure 2. ingenol mebutate gel 0.05% efficacy for treatment of warts 26 24 31 0 5 10 15 20 25 30 35 40 resolved p er ce nt a all treated n=54 non-occluded n=38 occluded n=16 44 42 45 0 5 10 15 20 25 30 35 40 45 50 category 1 p er ce nt all treated n=54 non-occluded n=38 occluded n=16 b complete clearance of all warts % wart size reduction subject satisfaction • 11 of the 16 subjects stated that the wart treatment was tolerable or very tolerable • 6 of the 16 subjects noted that the use of the bandage was moderately to extremely difficult during the 2 days of treatment • satisfaction with treatment results − neutral 7 of 16 subjects − moderately or very satisfied 5 of 16 subjects − disappointed 4 of 16 subjects • 7 of 16 subjects preferred this treatment over previous topical treatments or office procedures, with 5 strongly preferring and 2 slightly or moderately preferring this treatment asrs • asrs were defined as erythema, flaking/scaling, crusting, swelling, erosion/ ulceration and vesiculation/pustulation • all subjects experienced asrs that began on day 2 of treatment • asrs peaked within 8 days (figure 3) and resolved without relief treatment, with the exception of 2 subjects who required lysis of bullae • asrs most commonly reported as severe were swelling (3/16) and vesiculation/ pustulation (3/16) on day 8 follow-up • all asrs were clinically resolved at short-term follow-up at 3 to 4 weeks • no adverse effects were reported figure 3. photos of representative subjects treated for warts with ingenol mebutate gel 0.05% (a-f) a. day 1 before treatment occluded non-occluded b. day 2 occluded non-occluded c. day 8 occluded non-occluded d. day 57 occluded non-occluded e. day 1 day 2 f. day 8 day 57 courtesy of neal bhatia, md. discussion • the mechanism of action of ingenol mebutate in ak is often referred to as dual action: rapid lesion necrosis and then activation of the innate immune system via a specific neutrophil-mediated antibody-dependent cellular cytotoxicity5 • protein kinases play a fundamental role in the mechanism of action of ingenol mebutate treatment and the cell death of primary keratinocytes and patient-derived squamous cell carcinoma cells6 • hpv-infected keratinocytes behave similarly to uv-damaged keratinocytes in ak. given their similarities in mutagenesis and hyperproliferation,1,2,6 the cytotoxicity of target tissue with ingenol mebutate was hypothesized to be beneficial in wart destruction • the primary end point of complete clearance of all warts was not met in any of the 16 subjects in this study. however, overall wart count was reduced from 54 at baseline to 40 • of the occluded warts, 81.25% (13/16) were reduced in size from baseline, with 31% showing complete clearance (5/16) (figure 2) and 50% (8/16) showing a partial reduction in size. among the 38 non-occluded warts, fewer lesions were cleared: complete clearance was observed in 9 of these warts (24%), and 22 warts (57%) were reduced in size conclusion • ingenol mebutate gel 0.05% was efficacious and well tolerated for reducing the overall size of warts • the occluding treatment was associated with increased efficacy and anticipated asrs • the majority of subjects found the treatment to be tolerable or very tolerable references 1. lowy dr, androphy ej. warts. chapter 223. in: freedberg im, et al., eds. fitzpatrick’s dermatology in general medicine. vol 2. 6th ed. new york, ny: mcgraw-hill; 2003; 2119-2131. 2. lipke mm. clin med res. 2006;4(4):273-293. 3. picato® (ingenol mebutate) gel [package insert]. parsipanny, nj: leo pharma inc; 2016. 4. lebwohl m, et al. n engl j med. 2012;366:1010-1019. 5. rosen rh, et al. j am acad dermatol. 2012;66(3):484-493. 6. frieberger sn, et al. mol cancer ther. 2015;14(9):2132-2142. 7. schopf re. j eur acad dermatol venereol. 2015;30(6):1041-1043. acknowledgments we acknowledge the work of bethany parker, nicky yagubova, and dr. xochitl jimenez on this project. writing support was provided by p-value communications and funded by leo pharma inc. poster was originally presented at: maui derm for dermatologists; march 20-24, 2017; maui, hawaii. fc17posterleobhatiaanopenlabelexploratory.pdf tapinarof cream 1% once daily for plaque psoriasis: long-term extension trial of a novel therapeutic aryl hydrocarbon receptor modulating agent bruce strober,1 linda stein gold,2 robert bissonnette,3 april armstrong,4 andrew blauvelt,5 leon kircik,6,7 philip m. brown,8 anna m. tallman,8 mark lebwohl7 1yale university, new haven & central connecticut dermatology research, cromwell, ct, usa; 2henry ford health system, detroit, mi, usa; 3innovaderm research inc., montreal, qc, canada; 4keck school of medicine at university of southern california, los angeles, ca, usa; 5oregon medical research center, portland, or, usa; 6skin sciences pllc, louisville, ky, usa; 7icahn school of medicine at mount sinai, new york, ny, usa; 8dermavant sciences, inc., morrisville, nc, usa synopsis ■ in two 12-week pivotal phase 3 trials, psoaring 1 (nct03956355) and psoaring 2 (nct03983980), tapinarof cream 1% once daily (qd) demonstrated highly statistically and clinically significant efficacy versus vehicle and was well tolerated in adults with mild-to-severe plaque psoriasis1 ■ tapinarof cream 1% qd also demonstrated maintenance of efficacy for 4 weeks after treatment discontinuation in a 12-week phase 2b trial, warranting further investigation of a potential remittive effect2 objective ■ to present the results of psoaring 3 (nct04053387), a long-term extension trial designed to assess the safety, efficacy, durability of response, tolerability, and duration of remittive effect of tapinarof during repeated intermittent treatment, based on patient physician global assessment (pga) score methods study design ■ patients completing psoaring 1 and psoaring 2 were eligible to enroll in psoaring 3 for 40 weeks of open-label treatment with tapinarof cream 1% qd, followed by 4 weeks of follow-up (figure 1) ■ in psoaring 3, patients were treated with tapinarof cream 1% qd based on individual patient pga score: – patients who entered with a pga score of ≥1 received tapinarof cream 1% qd until complete disease clearance was achieved, defined as a pga score of 0 – patients who entered with, or achieved, a pga score of 0 discontinued treatment and were observed for remittive effect, defined as maintenance of a pga score of 0 (clear) or 1 (almost clear), while off therapy – if disease worsening occurred, defined as a pga score ≥2, tapinarof cream 1% qd was started and continued until a pga score of 0 (clear) was achieved figure 1. psoaring 3 study design four patients (3 tapinarof, 1 vehicle) did not have a baseline pga and are listed as missing. pga, physician global assessment; qd, once daily. endpoints and statistical analysis ■ safety: adverse events (aes), laboratory values, vital signs and physical exams ■ efficacy: – complete disease clearance: proportion of patients achieving pga of 0 (clear) – remittive effect: duration of efficacy maintenance defined as pga of 0 (clear) or 1 (almost clear) while off therapy after achieving complete disease clearance (pga=0) – response: proportion of patients who entered the trial with a pga≥2 and achieved a pga of 0 (clear) or 1 (almost clear) at least once during the trial – durability of response (absence of tachyphylaxis): maintenance of efficacy while on treatment, defined as the proportion of patients who achieved a pga score of 0 or 1 at least once during the trial, and trends in psoriasis area and severity index (pasi) score and percentage of body surface area (%bsa) affected over time ■ tolerability: local tolerability using a patient-reported 5-point scale for burning/stinging and itching, and an investigator-assessed 5-point scale for dryness, erythema, and peeling ■ efficacy analyses used observed case (oc) or last observation carried forward (locf) analysis that were based on the intention-to-treat (itt) population results baseline patient demographics and disease characteristics ■ overall, 763 (91.6%) eligible patients completing psoaring 1 and psoaring 2 opted to enroll in psoaring 3 ■ patient demographics and disease characteristics are summarized in table 1, including baseline values by prior treatment arm in the pivotal trials ■ overall, patients’ mean age was 50.7 years, 58.7% were male, mean weight was 92.4 kg and mean body mass index was 31.7 kg/m2 ■ patients previously randomized to tapinarof cream 1% qd (tapinarof→tapinarof) had lower baseline disease scores compared with the vehicle qd (vehicle→tapinarof) group, reflecting the significant efficacy of tapinarof in the pivotal studies – 14.6% (74/508) versus 2.0% (5/255) of patients had complete disease clearance (pga of 0), and 65.2% (331/508) versus 30.2% (77/255) of patients had a pga score of 1 (almost clear) or 2 (mild) in the tapinarof cream 1% qd pivotal group (tapinarof→tapinarof) versus the vehicle qd pivotal group (vehicle→tapinarof), respectively table 1. psoaring 3 baseline disease characteristics overall (n=763) tapinarof → tapinarof* (n=508) vehicle → tapinarof* (n=255) pga, n (%)† 0 – clear 79 (10.4) 74 (14.6) 5 (2.0) 1 – almost clear 161 (21.1) 144 (28.3) 17 (6.7) 2 – mild 247 (32.4) 187 (36.8) 60 (23.5) 3 – moderate 249 (32.6) 93 (18.3) 156 (61.2) 4 – severe 23 (3.0) 7 (1.4) 16 (6.3) pasi, mean (sd)† 4.8 (4.72) 3.3 (3.53) 7.7 (5.39) bsa affected, %, mean (sd)† 4.7 (5.60) 3.3 (4.74) 7.3 (6.21) *tapinarof→tapinarof: patients previously assigned to tapinarof in the pivotal trials who enrolled in psoaring 3; vehicle→tapinarof: patients previously assigned to vehicle in the pivotal trials who enrolled in psoaring 3. †four patients (3 previously assigned to tapinarof, 1 previously assigned to vehicle) did not have a baseline pga, pasi, and bsa value and are listed as missing. itt population. bsa, body surface area; itt, intention-to-treat; pasi, psoriasis area and severity index; pga, physician global assessment, sd, standard deviation. complete disease clearance (pga of 0) ■ overall, 40.9% (312/763) of patients achieved complete disease clearance at least once during the study; this included 233 patients who entered the study with a pga of ≥1, and 79 patients who entered with a pga of 0 (figure 2a) response among patients entering with a pga of ≥2 ■ overall, 58.2% (302/519) of patients entering the study with a pga of ≥2 achieved a pga of 0 (clear) or 1 (almost clear) at least once during the study (figure 2b) figure 2. complete disease clearance (pga=0) and response rates (pga=0 or 1) *including patients who entered with pga=0 (n=79) and patients entering with pga≥1 who achieved pga=0 at least once during the study (n=233). itt population, oc. itt, intention-to-treat; oc, observed cases; pga, physician global assessment. remittive effect: duration of efficacy maintenance among patients entering with a pga of 0 (n=79) ■ the duration of remittive effect (kaplan-meier estimated median, 95% confidence interval [ci]) while off therapy for patients who entered the study with a pga of 0 (clear) was 115.0 (95% ci; 85.0–168.0) days (figure 3) figure 3. duration of remittive effect among patients entering with a pga of 0: maintenance of a pga of 0 (clear) or 1 (almost clear) while off therapy itt population, oc. itt, intention-to-treat; oc, observed cases; pga, physician global assessment. total duration of remittive effect among patients entering with, or achieving, a pga of 0 (n=312) ■ the total duration of remittive effect (mean, standard deviation [sd]) while off therapy was 130.1 (89.4) days, a possible underestimate as study end, not disease worsening, truncated the duration for some patients durability of response ■ durability of response of up to 52 weeks was demonstrated with intermittent use of tapinarof cream 1% qd, indicating no observation of tachyphylaxis (defined as loss of response) while on therapy (figure 4) ■ patients previously treated with vehicle in the 12-week pivotal trials achieved similar responses to patients previously treated with tapinarof cream 1% qd (figure 4) figure 4. durability of response (no tachyphylaxis while on therapy) based on proportion of patients achieving a pga score of 0 (clear) or 1 (almost clear) at least once during the study *tapinarof→tapinarof: patients previously assigned to tapinarof in the pivotal trials who enrolled in psoaring 3; vehicle→tapinarof: patients previously assigned to vehicle in the pivotal trials who enrolled in psoaring 3. itt population, locf. itt, intention-to-treat; locf, last observation carried forward; pga, physician global assessment. ■ improvement in clinical response and remittive effect while off therapy of a patient with plaque psoriasis treated with tapinarof cream 1% qd (figure 5) figure 5. clinical response and remittive effect of a patient with plaque psoriasis treated with tapinarof cream 1% qd pga and pasi are global efficacy assessments. example of one representative target lesion of one tapinarof-treated patient from psoaring 1 and 3 clinical trials. individual results may vary. ‡lte week 24: off treatment for 12 weeks; lte week 36: off treatment for 24 weeks; re-treatment at lte week 36 due to disease worsening. lte, long-term extension; pasi, psoriasis area and severity index; pga, physician global assessment. safety ■ as previously reported, there were no new safety signals during the long-term safety trial3 and aes were consistent with previous studies1,2 ■ the most common treatment-emergent aes included folliculitis, contact dermatitis, and upper respiratory tract infection ■ study discontinuation due to folliculitis and contact dermatitis was low, 1.2% (9/763) and 1.4% (11/763), respectively, and similar to the rates observed in psoaring 1 and psoaring 21 conclusions ■ tapinarof cream 1% qd provided sustained improvement in efficacy endpoints with longterm intermittent use ■ a high rate of complete disease clearance (40.9%) and a remittive effect of approximately 4 months off therapy was demonstrated with tapinarof cream 1% qd, with no tachyphylaxis observed for up to 52 weeks ■ tapinarof cream 1% qd was well tolerated with long-term use and had a safety profile consistent with previous studies1,2 references 1. lebwohl m, et al. n engl j med. 2021;385:2219–2229; 2. robbins k et al. j am acad dermatol. 2019;80:714–721; 3. strober b, et al. innovations in dermatology virtual spring conference 2021, poster presentation, march 16–20, 2021. acknowledgments this study was funded by dermavant sciences, inc. the authors thank the participating investigators, patients and their families, and colleagues involved in the conduct of the study. b.s. has served as an honorary consultant/speaker/scientific director/investigator for abbvie, almirall, amgen, arcutis, arena, aristea, boehringer ingelheim, bristol-myers-squibb, cara, celgene, corrona psoriasis registry, dermavant sciences inc., dermira, equillium, janssen, leo, eli lilly, meiji seika pharma, mindera, novartis, pfizer, glaxosmithkline, ucb pharma, sun pharma, ortho dermatologics, regeneron and sanofi-genzyme. l.s.g has served as a consultant, and/or has received payment for the development of educational presentations, and/or has received grants from arcutis, amgen, bristol myers squibb, dermavant sciences, inc., eli lilly, leo pharma, ortho dermatologic, and ucb biopharma. r.b. has served as a consultant/advisory board member/speaker/investigator, and/or receives honoraria/grant from almirall, amgen, anaptysbio, arcutis, arena pharma, aristea, asana biosciences, bausch health, bellus health, bluefin biomedicine, boehringer-ingelheim, bristol-myers squibb, cara, dermavant sciences inc., eli lilly, emd serono, escalier, evidera, galderma, gsk, inmagene bio, incyte, janssen, kiniksa, kyowa kirin, leo pharma, nimbus, novan, pfizer, ralexar, rapt, regeneron, respivant, sanofi genzyme, sienna, target rwe, and ucb. r.b. is an employee and shareholder of innovaderm research. am is a research investigator and/ or scientific advisor to abbvie, bi, bms, epi, incyte, leo, ucb, janssen, lilly, novartis, ortho dermatologics, sun, dermavant sciences inc., dermira, sanofi, regeneron, pfizer, and modmed. a.b. has served as a scientific adviser and/or clinical study investigator for abbvie, abcentra, aligos, almirall, amgen, arcutis, arena, aslan, athenex, boehringer ingelheim, bristol-myers squibb, dermavant, eli lilly and company, evommune, forte, galderma, incyte, janssen, landos, leo, novartis, pfizer, rapt, regeneron, sanofi genzyme, sun pharma, and ucb pharma. l.k. has served as a consultant/speaker/investigator/advisory board member for abbott laboratories, abbvie, ablynx, aclaris, acambis, allergan, inc., almirall, amgen, inc., anacor pharmaceuticals, anaptys, arcutis, arena, assos pharma, astellas pharma us, inc., asubio, bausch health, berlex laboratories (bayer healthcare pharmaceuticals), biogen-idec, biolife, biopelle, bms, boehringer-ingleheim, breckinridge pharma, cassiopea, centocor, inc., cellceutix, cipher, coherus, colbar, combinatrix, connetics corporation, coria, dermavant sciences inc, dermira, dermik laboratories, dow pharmaceutical sciences, inc., dr. reddy’s lab, dusa, embil pharmaceuticals, eli lilly, eos, exeltis, ferndale laboratories, inc., foamix, ferrer, galderma, genentech, inc., glaxosmithkline, plc, glenmark, health point, ltd, idera, incyte, intendis, innocutis, innovail, isdin, johnson & johnson, kyowakirin, laboratory skin care inc., leo pharma, l’oreal, 3m, maruho, medical international technologies, merck, medicis pharmaceutical corp., merz, nano bio, novartis ag, nven pharmaceuticals, nucryst pharmaceuticals corp, obagi, onset, orthoneutrogena, pediapharma, pfizer, promius, puracap, pharmaderm, qlt, inc, quinnova, quatrix, regeneron, sanofi, serono (merck serono international sa), skinmedica, inc., stiefel laboratories, inc., sun pharma, taro, tolerrx, triax, ucb, valeant pharmaceuticals intl, warner-chilcott, xenoport, and zage. p.m.b. and a.n.t. are employees of dermavant sciences inc., with stock options. m.l. has received grants, and/or is a consultant for abbvie, amgen, aditum bio, almirall, altrubio inc., anaptysbio, arcutis, aristea therapeutics, arrive technologies, avotres, biomx, boehringer ingelheim, bristol-myers squibb, cara therapeutics, castle biosciences, corrona, dermavant sciences, dr. reddy’s laboratories, eli lilly, evelo biosciences, evommune, inc., facilitation of international dermatology education, forte biosciences, foundation for research and education in dermatology, helsinn therapeutics, hexima ltd., incyte, janssen research & development, leo pharma, llc, meiji seika pharma, mindera, ortho dermatologics, pfizer, regeneron, seanergy, ucb, inc., and verrica. editorial and medical writing support under the guidance of the authors was provided by apothecom, uk, and was funded by dermavant sciences, inc. in accordance with good publication practice (gpp3) guidelines (ann intern med. 2015;163:461–464). contact dr bruce strober at brucestrober30@me.com with questions or comments. a. complete disease clearance (pga=0) 60 50 40 30 20 10 0 overall (n=763) overall (n=519) 40.9* b. response (pga=0 or 1 among patients entering with a pga≥2) p ro p o rt io n o f p a ti e n ts , % 60 70 50 40 30 p ro p o rt io n o f p a ti e n ts , % 20 10 0 58.2 overall tapinarof→tapinarof* vehicle→tapinarof* p ro p o rt io n o f p a ti e n ts , % 0 10 20 30 40 50 60 70 0 4 8 12 16 20 weeknumber of patients overall tapinarof→tapinarof* vehicle→tapinarof* 759 505 254 725 479 246 682 455 227 652 432 220 627 419 208 596 394 202 576 385 191 570 381 189 552 366 186 548 368 180 541 365 176 24 28 32 36 40 overall (n=79) p ro b a b il it y o f d is e a se w o rs e n in g 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 number of patients overall 0 79 76 58 48 44 33 29 23 19 17 17 17 15 0 25 50 75 median time to pga≥2 115 days 100 125 150 175 time (days) 200 225 250 275 300 325 • • • pga=1 • pasi=3.8 off treatment for 24 weeks‡ • pga=2 • pasi=5.4 • pga=4 • pasi=19.8 off treatment for 12 weeks‡ • pga=1 • pasi=1.2 week 12 week 48 (lte week 36)‡ baseline week 36 (lte week 24)‡ psoaring 1 psoaring 3 (lte) long-term open-label extension (40 weeks) follow-up (4 weeks) double-blind treatment (12 weeks) off treatment off treatment pga=0 (n=79) pga=0 stop treatment pga≥2 re-start pga≥1 (n=680) tapinarof 1% qd pivotal (n=508) tapinarof 1% qd vehicle qd pivotal (n=255) conclusions clinical and health-related quality of life responses observed during the first two years of treatment were sustained to three years of treatment, regardless of bkz maintenance dose frequency prior to the third year. additionally, responses were sustained in the third year, regardless of all patients switching to bkz every 8 weeks. increases in responses after the ada to bkz switch were also sustained to week 152. bkz was well-tolerated over three years, with no unexpected safety findings. summary presented at the 42nd annual fall clinical dermatology conference | las vegas, nv | october 20–23, 2022 objectives to evaluate the long-term efficacy and safety of bimekizumab (bkz) over three years in patients with moderate to severe plaque psoriasis who enrolled in the be sure phase 3 trial and entered the be bright open-label extension (ole). introduction • in be sure (nct03412747), bkz demonstrated superior efficacy compared with adalimumab (ada) over 24 weeks. after patients switched from ada to bkz at week 24, responses improved and were maintained over two years, with no unexpected safety findings.1 • here, we consider long-term efficacy and safety over three years. materials and methods • treatment in be sure was as shown in figure 1. • upon completion of be sure, patients could enrol in the be bright ole (nct03598790; figure 1).1–3 • dose adjustments (to bkz 320 mg every 4 weeks [q4w] or every 8 weeks [q8w]) could occur at week 56 and week 80 (ole week 24) based on the achievement of ≥90% improvement from baseline in psoriasis area and severity index (pasi 90). all patients received bkz q8w from week 104 (ole week 48; or next clinic visit). • efficacy outcomes are reported for the intention-to-treat (itt) population through week 152 by initial randomisation group at be sure baseline. • data are reported using modified non-responder imputation (mnri), nri, and observed case (oc). – for mnri, patients who discontinued treatment due to lack of efficacy were considered non-responders at subsequent timepoints; multiple imputation was used for all other missing data. • safety data are reported for weeks 104–152 (data cut-off: 23 oct 2021), and include treatment-emergent adverse events (teaes) reported using exposure-adjusted incidence rates (eairs). two-year safety data have been reported previously (weeks 0–104).1,2 – the overview of adverse events and the most common teaes is reported both by initial randomization group regardless of bkz ole dosing regimen, and for all patients pooled (bkz total). bkz total was only used for safety topics of interest. results • in be sure, 478 patients were randomized 1:1:1 to: bkz q4w/q4w (n=158), bkz q4w/q8w (n=161), and ada/bkz q4w (n=159) (figure 1). baseline demographics have been reported previously and were aligned across treatment arms.2 • bkz-randomized patients maintained high levels of pasi 90 and pasi 100 responses to three years of treatment (week 152/ole week 96; figure 2; table 1). • among ada-randomized patients, the rapid increases seen in pasi 90 and pasi 100 responses for after the week 24 ada to bkz switch were durable to week 152, reaching similar levels to bkz-randomized patients (figure 2; table 1). • these trends were also reflected in dlqi 0/1 responses over three years (figure 2; table 1). • the most common teaes across bkz-treated patients were coronavirus infection, oral candidiasis, and nasopharyngitis (table 2). rates of safety topics of interest were low (table 3). • two coronavirus infections were reported as serious; of which only one was confirmed by testing. diamant thaçi,1 ron vender,2 menno de rie,3 curdin conrad,4 jennifer soung,5 bruce strober,6,7 maggie wang,8 nancy cross,8 delphine deherder,9 natalie nunez gomez,10 alice b. gottlieb11 bimekizumab efficacy and safety through three years in patients with moderate to severe plaque psoriasis: long-term results from the be sure randomized controlled trial and the be bright open-label extension previously presented at eadv 2022 institutions: 1institute and comprehensive center for inflammation medicine, university hospital of lübeck, lübeck, germany; 2dermatrials research inc., hamilton, ontario, canada; 3department of dermatology, amsterdam university medical centres, amsterdam, netherlands; 4department of dermatology, lausanne university hospital, switzerland; 5southern california dermatology, inc., santa ana, california, usa; 6yale university, new haven, connecticut, usa; 7central connecticut dermatology research, cromwell, connecticut, usa; 8ucb pharma, raleigh, north carolina, usa; 9ucb pharma, braine-l’alleud, belgium; 10ucb pharma, monheim, germany; 11department of dermatology, the icahn school of medicine at mount sinai, new york, new york, usa. references: 1thaçi d et al. presented at eadv 2021, p1324; 2warren rb et al. n engl j med 2021;385:130–41, nct03412747; 3be bright: clinicaltrials.gov/ct2/show/nct03598790. author contributions: substantial contributions to study conception/design, or acquisition/analysis/interpretation of data: dt, rv, mdr, cc, js, bs, mw, nc, dd, nng, abg; drafting of the publication, or revising it critically for important intellectual content: dt, rv, mdr, cc, js, bs, mw, nc, dd, nng, abg; final approval of the publication: dt, rv, mdr, cc, js, bs, mw, nc, dd, nng, abg. author disclosures: dt: honoraria for participation on advisory boards, as a speaker and for consultancy from abbvie, almirall, amgen, biogen, boehringer ingelheim, bristol myers squibb, celgene, celltrion, eli lilly, galapagos, janssen, leo pharma, morphosis, novartis, pfizer, regeneron, samsung, sanofi genzyme, sun pharma, and ucb pharma; research grants received from celgene, leo pharma, and novartis. rv: grants/research support: abbvie, amgen, centocor, dermira, dermavant, eli lilly, galderma, gsk, leo pharma, merck, novartis, pfizer, regeneron, takeda, and ucb pharma; speakers bureau/honoraria: abbvie, actelion, amgen, bausch health, celgene, cipher, eli lilly, galderma, gsk, janssen, leo pharma, merck, novartis, pfizer, and ucb pharma; consulting fees: abbvie, actelion, amgen, bausch health, celgene, cipher, eli lilly, galderma, gsk, janssen, leo pharma, merck, novartis, palladin, pfizer, and ucb pharma. mdr: honoraria for participation on advisory boards, as a speaker and for consultancy from abbvie, almirall, artax biopharma, biogen, celgene, eli lilly, janssen-cilag, janssen, leo pharma, novartis, and ucb pharma. cc: consultant and/or principal investigator in clinical trials for: abbvie, actelion, amgen, almirall, boehringer ingelheim, bristol myers squibb, celgene, eli lilly, galderma, incyte, janssen-cilag, leo pharma, msd, novartis, pfizer, samsung, sanofi genzyme, and ucb pharma. js: honoraria and/or consulting fees from amgen, celgene, dermavant, national psoriasis foundation, ortho dermatologics, and regeneron; grants and consulting fees from abbvie, actelion, boeringher ingelheim, dermira, eli lilly, janssen, leo pharma, novartis pharma, and ucb pharma; research grants from cassiopeia, galderma, and pfizer. bs: consultant (honoraria): abbvie, almirall, amgen, arcutis, arena, aristea, asana, boehringer ingelheim, bristol myers squibb, connect biopharma, dermavant, eli lilly, epi health, evelo biosciences, immunic therapeutics, janssen, leo pharma, maruho, meiji seika pharma, mindera health, novartis, ono, pfizer, regeneron, sanofi genzyme, sun pharma, ucb pharma, union therapeutics, ventyxbio, and vtv therapeutics; stock options: connect biopharma, mindera health; speaker: abbvie, eli lilly, janssen, regeneron, and sanofi genzyme; scientific co-director (consulting fee): corevitas (formerly corrona) psoriasis registry; investigator: abbvie, cara, corevitas psoriasis registry, dermavant, dermira, and novartis; editor-in-chief (honorarium): journal of psoriasis and psoriatic arthritis. mw, nc, dd: employees and shareholders of ucb pharma. nng: former employee and shareholder of ucb pharma, current employee of boehringer ingelheim. abg: honoraria as an advisory board member and consultant for: amgen, anaptysbio, avotres therapeutics, boehringer ingelheim, bristol myers squibb, dermavant, eli lilly, incyte, janssen, novartis, pfizer, sanofi, sun pharma, ucb pharma, and xbiotech (stock options for an ra project); research/educational grants from: anaptysbio, boehringer ingelheim, janssen, novartis, ortho dermatologics, sun pharma, and ucb pharma: all funds go to mount sinai medical school. acknowledgements: these studies were funded by ucb pharma. we thank the patients and their caregivers in addition to the investigators and their teams who contributed to these studies. the authors acknowledge susanne wiegratz, msc, ucb pharma, monheim, germany, for publication coordination, poppy wilson, mbiol, costello medical, london, uk, for medical writing and editorial assistance and the design team at costello medical for graphic design assistance. all costs associated with development of this poster were funded by ucb pharma. figure 1 study design figure 2 efficacy responses by randomized treatment group through week 152 (mnri) ada: adalimumab; bkz: bimekizumab; ci: confidence interval; dlqi: dermatology life quality index; eair: exposure-adjusted incidence rate; ibd: inflammatory bowel disease; itt: intention-to-treat; mace: major adverse cardiac event; mnri: modified non-responder imputation; nmsc: non-melanoma skin cancer; nri: non-responder imputation; oc: observed case; ole: open-label extension; pasi 90/100: ≥90%/100% improvement from be sure baseline in psoriasis area and severity index; py: patient-years; q4w: every 4 weeks; q8w: every 8 weeks; sib: suicidal ideation and behavior; teae: treatment-emergent adverse event. table 1 overview of efficacy outcomes (mnri, nri, oc) percentage of patients achieving pasi 90 at weeks 56, 104, and 152 (mnri) high initial pasi 90 response rates among bkz-randomized patients were maintained to week 152. additionally, pasi 90 response rates in patients switching from ada to bkz rapidly increased and were sustained over three years of treatment. there were no unexpected safety findings. bkz q4w/q4w; n=158 bkz q4w/q8w; n=161 ada/bkz q4w; n=159 0 100 80 60 40 20 week 56 week 104 week 152 p ro p o rt io n o f p a ti e n ts a c h ie v in g p a s i 9 0 ( % ) 92.6% 89.6% 94.3% 85.5% 87.3% 96.1%90.2% 89.0% 97.1% table 2 overview of adverse events during bkz treatment in patients from be sure who entered be bright, weeks 104–152 data to week 104 have been reported previously.1 data are presented for the itt population by initial randomization group. week 104 corresponds to ole week 48, and week 152 to ole week 96. bkz q4w/q4w n=158 bkz q4w/q8w n=161 ada/bkz q4w n=159 mnri, % nri, n (%) oc, n/n (%) mnri, % nri, n (%) oc, n/n (%) mnri, % nri, n (%) oc, n/n (%) pasi 90 week 56 92.6 134 (84.8) 134/140 (95.7) 89.6 133 (82.6) 133/143 (93.0) 94.3 130 (81.8) 130/133 (97.7) week 104 90.2 121 (76.6) 121/129 (93.8) 89.0 119 (73.9) 119/126 (94.4) 97.1 121 (76.1) 121/123 (98.4) week 152 85.5 113 (71.5) 113/123 (91.9) 87.3 110 (68.3) 110/115 (95.7) 96.1 112 (70.4) 112/114 (98.2) pasi 100 week 56 78.3 114 (72.2) 114/140 (81.4) 75.8 113 (70.2) 113/143 (79.0) 74.0 106 (66.7) 106/133 (79.7) week 104 72.0 102 (64.6) 102/129 (79.1) 67.5 101 (62.7) 101/126 (80.2) 71.3 98 (61.6) 98/123 (79.7) week 152 65.8 95 (60.1) 95/123 (77.2) 62.3 89 (55.3) 89/115 (77.4) 69.2 92 (57.9) 92/114 (80.7) dlqi 0/1 week 56 78.5 117 (74.1) 117/140 (83.6) 81.9 127 (78.9) 127/142 (89.4) 81.0 116 (73.0) 116/132 (87.9) week 104 80.8 112 (70.9) 112/130 (86.2) 82.1 110 (68.3) 110/126 (87.3) 82.0 112 (70.4) 112/124 (90.3) week 152 77.1 101 (63.9) 101/121 (83.5) 81.4 103 (64.0) 103/115 (89.6) 78.0 101 (63.5) 101/112 (90.2) two-year safety data have been reported previously (weeks 0–104).1,2 data are presented as eairs of new cases per 100 patient-years from weeks 104–152 for all patients who received ≥1 bkz dose in the week 104–152 period (data cut-off: 23 oct 2021), both by initial randomization group regardless of bkz ole dosing regimen, and for all patients pooled (bkz total). all patients received bkz q8w from week 104 (ole week 96; or next visit). avalues in bold are the three most common teaes for the treatment group. eair/100 py (95% ci) bkz total n=380 bkz q4w/q4w n=132 bkz q4w/q8w n=124 ada/bkz q4w n=124 any teae 101.7 (88.7, 116.0) 108.0 (85.5, 134.6) 99.4 (77.6, 125.4) 97.6 (76.2, 123.1) serious teaes 6.2 (3.9, 9.5) 5.1 (1.9, 11.1) 8.2 (3.7, 15.5) 5.5 (2.0, 11.9) discontinuation due to teaes 2.9 (1.4, 5.4) 2.5 (0.5, 7.4) 3.5 (1.0, 9.1) 2.7 (0.6, 7.9) severe teaes 5.0 (2.9, 8.0) 3.4 (0.9, 8.7) 8.2 (3.7, 15.5) 3.6 (1.0, 9.2) deaths 1.2 (0.3, 3.0) 1.7 (0.2, 6.1) 0.9 (0.0, 4.9) 0.9 (0.0, 5.0) most common teaesa coronavirus infection 6.6 (4.1, 10.0) 5.2 (1.9, 11.3) 8.3 (3.8, 15.8) 6.4 (2.6, 13.3) nasopharyngitis 4.8 (2.7, 7.7) 4.3 (1.4, 10.1) 2.7 (0.6, 7.8) 7.4 (3.2, 14.6) oral candidiasis 6.3 (3.9, 9.7) 6.1 (2.5, 12.6) 7.3 (3.2, 14.4) 5.6 (2.0, 12.1) urinary tract infection 3.5 (1.8, 6.2) 3.4 (0.9, 8.8) 5.4 (2.0, 11.7) 1.8 (0.2, 6.6) eair/100 py (95% ci) bkz total (n=380) serious infections 1.8 (0.6, 3.8) active tuberculosis 0.0 ibd 0.6 (0.1, 2.1) malignancies 0.6 (0.1, 2.1) nmsc 0.0 adjudicated sib 0.0 serious hypersensitivity reactions 0.0 adjudicated mace 0.9 (0.2, 2.6) elevated liver enzymes 3.2 (1.6, 5.8) two-year safety data have been reported previously (weeks 0–104).1,2 data are presented as eairs of new cases per 100 patient-years from weeks 104–152 for all patients who received ≥1 bkz dose in the week 104–152 period (data cut-off: 23 oct 2021) for all patients pooled (bkz total). all patients received bkz q8w from week 104 (ole week 96; or next visit). in be sure, patients were randomized 1:1:1 to: bkz 320 mg q4w for 56 weeks; bkz 320 mg q4w for 16 weeks then q8w through weeks 16–56; or ada 40 mg q2w for 24 weeks followed by bkz 320 mg q4w to week 56. at week 56, dose adjustments (to bkz 320 mg q4w or q8w) could occur based on whether patients achieved pasi 90. patients receiving bkz 320 mg q4w at week 56 who achieved pasi 90 were randomized 4:1 to bkz 320 mg q4w or q8w. at week 24 of be bright, for patients receiving bkz 320 mg q4w, if pasi 90 was achieved, the investigator could change the patient’s dosing interval from 320 mg q4w to 320 mg q8w. all patients were switched to bkz 320 mg q8w at the next scheduled clinic visit on or after the week 104 visit (ole week 48) following protocol amendment. be sure be bright screening initial treatment period maintenance period open-label treatment period n=478 1:1:1 randomization bkz 320 mg q8w bkz 320 mg q4w bkz 320 mg q4w bkz 320 mg q4w bkz 320 mg q4w bkz 320 mg q4w bkz 320 mg q4w bkz 320 mg q8w bkz 320 mg q8w bkz 320 mg q8w ada 40 mg q2w n=158 n=161 n=159 <pasi 90 <pasi 90 <pasi 90 ≥pasi 90 ≥pasi 90 ≥pasi 90 4:1 4:1 ≥pasi 90 ≥pasi 90 ≥pasi 90 investigator discretion investigator discretion investigator discretion ole week 48 or next scheduled visit ole week 48 or next scheduled visit ole week 48 or next scheduled visit baseline 2–5 weeks week 16 week 24 ole week 0 (week 56) ole week 96 (week 152) ole week 48 (week 104) ole week 24 (week 80) table 3 safety topics of interest (bkz total) data are presented for the itt population by initial randomisation group. the vertical line at week 24 indicates when patients randomized to ada switched to bkz q4w. week 104 corresponds to ole week 48, and week 152 to ole week 96. bkz q4w/q4w; n=158 bkz q4w/q8w; n=161 ada/bkz q4w; n=159 0 25 50 75 100 p ro p o rt io n o f p a ti e n ts a c h ie v in g p a s i 9 0 ( % ) 0 8 16 24 32 40 48 56 64 72 80 88 96 104 112 120 152144136128 week open-label period with possible dose adjustments 89.4% 50.1% 94.3% 92.6% 90.2% 85.5% 91.2% 89.6% 97.1% 89.0% 96.1% 87.3% 0 25 50 75 100 p ro p o rt io n o f p a ti e n ts a c h ie v in g p a s i 1 0 0 ( % ) open-label period with possible dose adjustments 62.8% 26.0% 74.0% 75.8% 71.3% 67.5% 69.2% 62.3% 0 8 16 24 32 40 48 56 64 72 80 88 96 104 112 120 152144136128 week 78.2% 61.6% 72.0% 65.8% 0 25 50 75 100 p ro p o rt io n o f p a ti e n ts a c h ie v in g d l q i 0 /1 ( % ) open-label period with possible dose adjustments 66.6% 48.1% 81.0% 81.9% 82.0% 82.1% 78.0% 81.4% 0 8 16 24 32 40 48 56 64 72 80 88 96 104 112 120 152144136128 week 77.1%80.8%78.5% 63.8% a) pasi 90 b) pasi 100 c) dlqi 0/1 skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 210 original research diagnostic efficacy of electrical impedance spectroscopy versus dermoscopy for pigmented skin lesions: a pilot study shayan owji1, bs, joseph han1, bs, helen he1, md, isabel lopera1, bs, michael tassavor1, md, nicholas brownstone2, md, nicholas gulati1, md, phd, benjamin ungar1, md, jonathan ungar1, md 1 department of dermatology, icahn school of medicine at mount sinai, new york, ny 2 national society for cutaneous medicine, new york, ny it is critical for dermatology providers to accurately identify concerning pigmented skin lesions (psls) for biopsy, while avoiding biopsies for benign psls. evidence shows that early recognition and removal of melanocytic neoplasms remains the most impactful prognostic factor for favorable melanoma outcomes.1,2,3 currently, dermatologists largely rely on visual inspection and dermoscopic examination to guide clinical decision-making for psls. however, this approach is not infallible: false positive diagnoses lead to unnecessary excisions, complications, and increases in health care costs; of even greater clinical concern, false negative diagnoses can leave malignant lesions undiagnosed, increasing patient mortality.4,5 abstract introduction: electrical impedance spectroscopy (eis) is a non-invasive diagnostic device that measures the electrical impedance of skin lesions to assist in the detection of melanoma. while this tool has been shown to have a high sensitivity for melanoma diagnosis, data on its impact on clinical decision-making for pigmented skin lesions (psls) compared to other diagnostic tools is lacking. to gain further insight into its clinical utility, we conducted a pilot study to evaluate how this technology – specifically, the effect it has on clinical decisions for psls – compares to traditional dermoscopy. methods: dermatologists, dermatology residents, and medical students completed an online survey eliciting their biopsy decisions for 24 psls of varying histopathological diagnoses. half of the lesions from each diagnosis group were presented as a clinical image with associated dermoscopic image and the other half as a clinical image with the corresponding eis score. results: decisions made with eis demonstrated a mean sensitivity of 75% for melanomas/severely dysplastic nevi vs. 66% for decisions made with dermoscopy (p=.008). while dermatologists biopsied with similar sensitivities when using eis or dermoscopy (81% vs. 81%), residents and medical students biopsied with significantly greater sensitivity when using eis. respondents who reported rarely using dermoscopy showed the greatest improvement in sensitivity and specificity when using eis compared to dermoscopy. conclusion: given that not all providers are trained in dermoscopy, and our finding that eis particularly benefits those who infrequently use dermoscopy, eis may complement dermoscopy by helping a broader range of providers make improved psl diagnostic decisions. introduction skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 211 electrical impedance spectroscopy (eis) technology is a noninvasive, point-of-care diagnostic tool designed to aid clinicians in the decision to biopsy psls. approved by the us food and drug administration to assist in the detection of melanoma, the eis device (nevisense, scibase, stockholm, sweden) utilizes a small, low voltage electrode to apply a painless electrical current to the skin.6 as benign and malignant tissues vary in cell shape, size, and molecular composition, eis can measure the resulting differences in electrical impedance of different psls and generate scores correlating to the risk of malignancy. the device produces a score ranging from 0 to 10, which is associated with the likelihood that the tested lesion is a melanoma.6 eis scores of 0 to 3 carry a negative predictive value of 99%, while those from 4 to 10 represent progressively increasing positive predictive values ranging from 7% to 61%.7 past studies evaluating the clinical utility of eis have gathered some promising preliminary data, suggesting that it increases the sensitivity and specificity of dermatologists’ biopsy decisions for melanoma compared with visual inspection alone.7,8 the number needed to biopsy (nnb), a biopsy efficiency metric denoting the ratio of total biopsies to melanomas detected, also decreased when eis use supplemented clinical decision-making on the basis of clinical morphology alone.7 while these studies have demonstrated that incorporating eis into clinical decisionmaking for psls is superior to just visual clinical inspection alone, the diagnostic efficacy of eis has yet to be compared head-to-head with that of dermoscopy, currently used as standard practice by dermatologists in evaluation of psls. to better understand the clinical utility of eis, we investigated how this relatively new technology – specifically, the effect it has on clinical decisions for psls – compares to traditional dermoscopy. our survey for dermatologists, dermatology residents, and medical students compared clinical decision-making with eis vs. dermoscopy. participants were recruited via email over a period of 2 months. images of twenty-four randomly selected, histologically-confirmed and eis-evaluated psls, comprising 8 melanomas, 8 dysplastic nevi (6 mild-moderate dysplastic, 2 severe dysplastic), and 8 melanocytic nevi, from a previously published prospective blinded trial of 2416 lesions were included in this study.6 twelve psls (half of the lesions from each diagnosis group) were randomly selected to be presented as a clinical image with associated dermoscopic image (dermoscopy group), while the other twelve lesions were presented as a clinical image with the corresponding eis score (eis group). after evaluating each lesion, respondents rated the necessity of a biopsy on a scale from 1-5 (1: ‘not necessary’, 5: ‘extremely necessary’). a selection of 4 or 5 was considered to be a decision to biopsy, with 1-3 considered a decision not to biopsy. the sensitivity and specificity of biopsy decisions for melanomas and severely dysplastic nevi were determined. these metrics were further compared between different subsets of the respondent population by stratifying the population into groups based on their level of training and the frequency with which they use dermoscopy in clinical practice. methods skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 212 differences in biopsy decision proportions, sensitivities, and specificities were compared using pearson’s chi-squared test. significance between the area under the curves (aucs) of the receiver operating characteristic (roc) curves was calculated using the bootstrap method computed with 2,000 replicates. eighty-nine participants (38 dermatologists, 25 dermatology residents, and 26 medical students) provided responses, making a total of 1740 clinical decisions (862 in the dermoscopy group, 878 in the eis group). with dermoscopy, the decision to biopsy was made for 541 of 862 lesions vs. 422 of 878 lesions with eis (62.8% vs. 48.1%, respectively; p<0.001; table 1). biopsy decisions made with dermoscopy demonstrated an overall sensitivity of 66% compared with a sensitivity of 75% with eis (p=0.008; table 2). similarly, biopsy decisions made with eis yielded a greater specificity (70%) than dermoscopy (40%; p<0.001). biopsy decisions were impacted by training level, with dermatologists exhibiting similar sensitivities with both eis and dermoscopy (81% vs. 81%). however, dermatologists also saw the greatest increase (68% vs. 35%, p<0.001) in the specificity of biopsy decisions made with eis when compared to dermoscopy. residents and medical students biopsied with significantly greater sensitivity and specificity when using eis compared to dermoscopy. conducting a receiver operating characteristic (roc) analysis using different biopsy ratings (1-5) as varying thresholds demonstrated that with clinical photography, eis produced an area under the curve (auc) of 0.78, which was significantly greater than the auc produced with dermoscopy (0.527; p<0.001; figure 1). in each of the four strata representing varying frequencies of respondents’ dermoscopy usage, greater sensitivities and specificities were noted in biopsy decisions made using eis than those made using dermoscopy (table 3). the greatest difference was among those who rarely or never use dermoscopy, who made biopsy decisions with 13% greater sensitivity and 35% greater specificity using eis compared to dermoscopy (p=0.067 and p<0.001, respectively). figure 1. melanoma detection often poses a challenge to dermatologists, especially in patients with multiple nevi. the clinical evaluation of psls involves consideration of lesion-specific information as well as patientderived melanoma risk factors.9 even when utilizing all available clinical information, clinicians still occasionally find themselves results discussion skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 213 misdiagnosing melanomas as benign lesions.10 given the impact of early detection and treatment of melanoma on patient outcomes,1 improved evaluation tools may help clinicians to both reduce patient morbidity associated with unnecessary excision of benign lesions, as well as potentially reduce mortality by enhancing detection of malignant lesions. the value of a diagnostic tool lies in its ability to increase accuracy and positively impact clinical management: increased sensitivity reduces the false negatives of missed melanomas, while increased specificity avoids unnecessary biopsies of benign lesions. in this study, which aimed to compare the individual influences of eis and dermoscopy on clinical decision-making, eis-assisted decisions demonstrated greater accuracy than those made using dermoscopy. training level had a noticeable impact on the results observed. of the three different levels of training included, all but table 1. number of decisions to biopsy out of total clinical decisions made both based on visual plus dermoscopic examination and visual plus eis evaluation across different training levels of the respondent population. training level dermoscopy eis p valuea decisions to biopsy, n (%) total clinical decisions made (n) decisions to biopsy, n (%) total clinical decisions made (n) dermatologists (n=38) 256 (71.9) 356 188 (51.6) 364 <0.001 dermatology residents (n=25) 152 (60.6) 251 132 (51.8) 255 0.046 medical students (n=26) 133 (52.2) 255 102 (39.4) 259 0.004 total (n=89) 541 (62.8) 862 422 (48.1) 878 <0.001 eis, electrical impedance spectroscopy a chi-squared test table 2. sensitivity and specificity of biopsy decisions for melanomas and severely dysplastic nevi both based on visual plus dermoscopic examination and visual plus eis evaluation across different training levels of the respondent population training level dermoscopy eis p value, sens.c p value, spec.c tp (n) fn (n) sens.a % (95% ci) tn (n) fp (n) spec.b % (95% ci) tp (n) fn (n) sens.a % (95% ci) tn (n) fp (n) spec.b % (95% ci) dermatologists (n=38) 120 28 81 (75.8– 86.4) 72 136 35 (27– 42.3) 118 29 81 (75– 85.6) 147 70 68 (60.2– 75.3) 0.86 <0.001 dermatology residents (n=25) 64 40 62 (53.7– 69.4) 59 88 40 (30.7– 49.6) 83 20 81 (74.2– 86.9) 103 49 68 (58.7– 76.8) 0.003 <0.001 medical students (n=26) 52 53 50 (41.5– 57.5) 69 81 46 (36.5– 55.5) 65 39 63 (54.9– 70.1) 118 37 76 (67.9– 84.3) 0.05 <0.001 total (n=89) 236 121 66 (62– 70.2) 200 305 40 (34.5– 44.7) 266 88 75 (71.4– 78.8) 368 156 70 (65.5– 75) 0.008 <0.001 skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 214 eis, electrical impedance spectroscopy; fn, false negatives; fp, false positives; tn, true negatives; tp, true positives a sensitivity of biopsy/referral decisions for melanomas and severely dn, calculated as tp/(tp+fn) b specificity of biopsy/referral decisions for melanomas and severely dn, calculated as tn/(tn+fp) c chi-squared test table 3. sensitivity and specificity of biopsy decisions for melanomas and severely dysplastic nevi both based on visual plus dermoscopic examination and visual plus eis evaluation across varying dermoscopy use frequencies of the respondent population. dermoscopy usage frequency dermoscopy eis p value, sens.c p value, spec.c tp (n) fn (n) sens.a % (95% ci) tn (n) fp (n) spec.b % (95% ci) tp (n) fn (n) sens.a % (95% ci) tn (n) fp (n) spec.b % (95% ci) very frequently (multiple times/day) 133 47 74 (68.5– 79.3) 87 166 34 (27.4– 41.3) 146 33 82 (76.9– 86.2) 179 82 69 (61.8– 75.4) 0.081 <0.001 frequently (multiple times/week) 32 14 70 (58.3– 80.8) 28 36 44 (29.4– 58.1) 36 9 80 (70.5– 89.5) 40 28 59 (44.4– 73.2) 0.252 0.083 less frequently (multiple times/month) 23 12 66 (52.4– 79) 22 27 45 (28.4– 61.3) 24 11 69 (55.7– 81.4) 33 17 66 (50.3– 81.7) 0.799 0.035 rarely or never 48 48 50 (41.7– 58.3) 63 76 45 (35.4– 55.3) 60 35 63 (55.3– 71) 116 29 80 (72– 88) 0.067 <0.001 eis, electrical impedance spectroscopy; fn, false negatives; fp, false positives; tn, true negatives; tp, true positives a sensitivity of biopsy/referral decisions for melanomas and severely dn, calculated as tp/(tp+fn) b specificity of biopsy/referral decisions for melanomas and severely dn, calculated as tn/(tn+fp) c chi-squared test dermatologists saw an increase in the sensitivity of their biopsy decisions with eis compared to dermoscopy, and all three saw increases in their specificity with eis compared to dermoscopy. while dermatologists’ biopsy decisions exhibited similar sensitivities with both eis and dermoscopy, this group also saw the greatest improvement in the specificity of their biopsy decisions with eis when compared to dermoscopy. this indicates that dermatologists in this study, while still biopsying with the greater sensitivity, were more likely than residents and medical students to biopsy benign lesions when using dermoscopy, leading to a lower specificity of their dermoscopy-assisted biopsy decisions. eis served to reduce the number of benign biopsies made by this group, increasing their specificity considerably and maintaining sensitivity. given eis’ high observed npv of 99%,6 it is conceivable that lesions receiving a “negative” eis score (0 to 3), which would have otherwise been biopsied based on visual and dermoscopic criteria, are responsible for this rise in specificity. those who rarely used dermoscopy appeared to benefit more from eis than their counterparts with greater dermoscopy experience, with this group demonstrating the greatest improvement in both sensitivity and specificity when using eis compared to skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 215 dermoscopy. this finding suggests eis may be of particular benefit to clinicians less proficient in dermoscopy. of note, the eis sensitivities (75% overall, 81% among attendings) detected in this study are less than that in the eis pivotal trial (97%), while the specificities observed (70% overall, 68% among attendings) are higher than that in the pivotal trial (34%).6 this may be attributed to our survey format, in which respondents rated their inclination to biopsy each lesion from 1-5. for our analysis, lesions rated 1-3 were considered as unbiopsied and those rated 45 as biopsied. in comparison to the pivotal trial’s binary biopsy choice, this approach may have yielded a greater number of lesions deemed unbiopsied, thus lowering the sensitivity, and fewer lesions biopsied, thus raising the specificity. this approach was applied equally to dermoscopyand eis-assisted biopsy decisions, however, so relative accuracy would not have been affected. in clinical practice, tools to assist in accurately identifying ambiguous lesions to biopsy would have the greatest yield in diagnosing melanomas without biopsying benign lesions. the significantly greater auc of eis-assisted biopsy decisions demonstrates that eis improved accuracy across all levels of biopsy confidence. however, this study had limitations. one limitation is that respondents’ biopsy decisions were made on the basis of clinical images in an online survey rather than in vivo examination. as such, the true consequences of a missed melanoma or an unnecessary biopsy were likely diminished compared to lesions examined in a real clinical setting. this survey also did not include nonmelanocytic lesions such as seborrheic keratoses, which could alter the accuracy of eis-based biopsy decisions. lastly, inherent to survey-based studies is the potential for participation bias. implementing the use of diagnostic tools that improve accuracy in malignant psl detection is crucial to improve patient outcomes and reduce unnecessary biopsies. in this pilot study, we found that dermatologists made biopsy decisions with similar sensitivity when utilizing either eis or dermoscopy. however, those with comparably less dermoscopy experience (i.e. residents, medical students) demonstrated significantly improved sensitivity when using eis compared to dermoscopy. given that not all providers are trained in dermoscopy, and our finding that eis particularly benefits those who infrequently use dermoscopy, eis may complement dermoscopy by helping a broader range of providers make improved psl diagnostic decisions. this will ultimately improve patient care and reduce the morbidity and mortality of a melanoma diagnosis. conflict of interest disclosures: none funding: none corresponding author: jonathan ungar, md department of dermatology icahn school of medicine at mount sinai 5 e. 98th street, new york, ny 10029 phone: 212-241-9728 fax: 212-978-1197 email: jonathan.ungar@mountsinai.org references: 1. glazer am, rigel ds, winkelmann rr, farberg as. clinical diagnosis of skin cancer: enhancing inspection and early recognition. dermatol clin. 2017 oct;35(4):409-416. conclusion mailto:jonathan.ungar@mountsinai.org skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 216 2. terushkin v, halpern ac. melanoma early detection. hematol oncol clin north am. 2009 jun;23(3):481-500, viii. 3. leachman sa, cassidy pb, chen sc, curiel c, geller a, gareau d, pellacani g, grichnik jm, malvehy j, north j, jacques sl, petrie t, puig s, swetter sm, tofte s, weinstock ma. methods of melanoma detection. cancer treat res. 2016;167:51-105. 4. papageorgiou v, apalla z, sotiriou e, et al. the limitations of dermoscopy: false-positive and false-negative tumours. j eur acad dermatol venereol. 2018;32(6):879-888. 5. chiaravalloti aj, laduca jr. melanoma screening by means of complete skin exams for all patients in a dermatology practice reduces the thickness of primary melanomas at diagnosis. j clin aesthet dermatol. 2014 aug;7(8):18-22. 6. malvehy j, hauschild a, curiel-lewandrowski c, et al. clinical performance of the nevisense system in cutaneous melanoma detection: an international, multicentre, prospective and blinded clinical trial on efficacy and safety. br j dermatol. 2014;171(5):1099-1107. 7. litchman gh, teplitz rw, marson jw, rigel ds. impact of electrical impedance spectroscopy on dermatologists' number needed to biopsy metric and biopsy decisions for pigmented skin lesions. j am acad dermatol. 2021 oct;85(4):976-979. 8. svoboda rm, prado g, mirsky rs, rigel ds. assessment of clinician accuracy for diagnosing melanoma on the basis of electrical impedance spectroscopy score plus morphology versus lesion morphology alone. j am acad dermatol. 2019 jan;80(1):285-287. 9. rastrelli m, tropea s, rossi cr, alaibac m. melanoma: epidemiology, risk factors, pathogenesis, diagnosis and classification. in vivo. 2014 nov-dec;28(6):1005-11. 10. guitera p, menzies sw. state of the art of diagnostic technology for early-stage melanoma. expert rev anticancer ther. 2011 may;11(5):715-23. skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 265 brief articles persistent chloracne in a tank mechanic austin ambur do,1 andrew newman do,2 jason barr do,2 travis lam do2 1advanced dermatology and cosmetic surgery/kcu-gme consortium 2affiliated dermatology/honor health a 74-year-old male presented to our dermatology office for a routine skin check with an impressive acneiform eruption over his face. he stated that his acne lesions developed after 35 years of age and have persisted since this time, having denied a history of significant acne in his teenage years. the patient retired 14 years ago from his career as a military tank mechanic. physical examination showed numerous large closed and open comedones and noninflamed cystic structures located over the face and bilateral post-auricular skin (figure 1 and figure 2). he denied an examination of his genitals. the patient did not have any significant past medical history or chronic illnesses and was not taking any medications or supplements. the authors believe this to be most consistent with chloracne, which is more descriptively known as metabolizing acquired dioxin-induced skin hamartomas (madish). figure 1. large closed and open comedones and non-inflamed cystic structures on the face case report chloracne is characterized by acquired dioxin-induced skin hamartomas (madish), often involving the post-auricular skin. chloracne classically occurs in individuals exposed to agent orange and dioxin-containing oils used in machinery. since new-onset acne vulgaris is unusual in adults, a thorough occupational history must be elicited in this patient population. the herein patient is a retired tank mechanic with no known exposure to agent orange and presents with persistent acneiform eruptions. abstract skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 266 figure 2. large closed and open comedones and non-inflamed cystic structures on the face most cases of madish are due to occupational and environmental exposure to dioxin or similar toxic halogenated aromatic hydrocarbons. these are most often found in fungicides, insecticides, herbicides, and wood preservatives. one of the most popular sources of dioxin came from agent orange, commonly used during the vietnam war. our patient denied direct exposure to agent orange, but was possibly exposed to dioxin or similar chloracnegens via his work with tank machinery. acute exposure to dioxin and similar chloracnegens may cause fatigue, anorexia, liver dysfunction, and neuropathy.1 with further progression of the condition, the chemical is thought to redistribute into the fat cells and sebaceous glands where it is concentrated and slowly metabolized. through this process, the gland alters its gene expression to upregulate cyp1a1 and it transforms into the cutaneous hamartoma seen in chloracne.2 chloracne is classically characterized by open and closed comedones and cysts on the cheeks, behind the ears, in the armpits and in the groin.1 the diagnosis is primarily based on the patient history and clinical examination. chloracne is a chronic condition and the clinical course depends on the intensity and duration of exposure. chloracne is typically difficult to manage because it is highly resistant to treatment. the most commonly recommended treatment regimen includes removing the source of dioxin exposure and symptomatic care.2 although there have been reports that isotretinoin, dermabrasion, and light electrodessication may be beneficial in the treatment of chloracne, the condition remains to be mostly treatmentresistant.3 we present a case of chloracne to highlight the unique clinical characteristics and bring awareness to the difficulty of treatment. we also use this case to highlight the variability in disease duration. most cases have reported that the lesions typically regress and heal over time.4 however, similar to what this patient has experienced, other reports have shown that chronic chloracne disease can persist up to 30 years after an exposure to dioxin-related chemicals. 5 conflict of interest disclosures: none funding: none corresponding author: austin ambur, do advanced dermatology and cosmetic surgery/ kcu-gme consortium email: austin.b.ambur@gmail.com discussion mailto:austin.b.ambur@gmail.com skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 267 references: 1. ju q, kuochia y, zoubolis cc, et al. environmental pollution and acne: chloracne. dermatoendocrinol. 2009. vol 1(3). 125-8 pp. 2. patterson at, kaffenberger bh, keller ra, elston dm. skin diseases associated with agent orange and other organochlorine exposures. j am acad dermatol. 2016. vol 74(1).143-70. 3. qiang ju, kuochia y, zouboulis cc, et al. chloracne: from clinic to research. dermatologica sinica. 2012. vol 30(1). 2-6 pp. 4. veterans and agent orange: health effects of herbicides used in vietnam. 1994;. doi: 10.17226/2141. review. pubmed pmid: 25144022. 5. suskind rr, hertzberg vs. human health effects of 2,4,5-t and its toxic contaminants.jama. 1984 may 11;251(18):2372-80. pubmed pmid: 6231388. skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 20 original research impact of electrical impedance spectroscopy on clinician confidence and diagnostic accuracy in evaluating melanocytic skin lesions suspicious for melanoma: a pilot study avani kolla, bphil1, lauren fried, md1*, payal shah, md1*, tracey liebman, md1, jennifer stein, md, phd1,2, david polsky, md, phd1,2 *authors contributed equally and are listed alphabetically 1 the ronald o. perelman department of dermatology, nyu grossman school of medicine, new york, ny 2 the laura and isaac perlmutter cancer center, nyu langone health, new york, ny there has been growing interest in the development of non-invasive modalities such as dermoscopy, nevisense (scibase), and the pigmented lesion assay (dermtech) to facilitate the evaluation of lesions concerning for skin cancer, particularly melanoma 1-7. the primary goal of these devices has been high levels of diagnostic accuracy in the identification of early stage melanomas, while maintaining low biopsy rates of benign lesions. to date, few studies have examined how these modalities impact diagnostic confidence 8. the impact on clinician abstract introduction: nevisense is a non-invasive device that measures electrical impedance spectroscopy (eis) of individual skin lesions to aid in the diagnosis of melanoma. while eis has demonstrated high sensitivity in diagnosing melanoma, its impact on a clinician’s diagnostic confidence remains unknown. objective: to conduct a pilot study to evaluate whether clinician diagnostic confidence, sensitivity, specificity and accuracy can be increased by adding eis measurement scores to clinical and dermoscopic images of lesions clinically suspicious for melanoma. methods: three pigmented lesions specialists and three 4th year medical students completed an online survey to evaluate 34 melanocytic lesions suspicious for melanoma. for each lesion, participants provided their diagnosis, biopsy recommendation, and confidence in diagnosing a lesion as benign or malignant based on history and clinical and dermoscopic images, and again after receiving an eis score. results: addition of eis scores increased mean biopsy sensitivity for melanoma/severely dysplastic nevi from 70% to 84% (p = .014) and mean diagnostic accuracy from 74% to 86% (p = .005). mean diagnostic confidence increased for all histopathologic categories for both students and dermatologists (all p < .05). conclusions: in this pilot study, eis increased novice and expert diagnosticians’ confidence regarding dermoscopically equivocal melanocytic lesions. further studies are needed to explore how eis can help clinicians reassure patients regarding the management of clinically dysplastic melanocytic nevi. introduction skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 21 confidence is important. confidence is defined as having trust and belief in oneself 9. it plays a crucial role in decision-making, and may even impact the duration of the decision-making process, especially when the accuracy of the decision is important 10. confidence is also thought to influence the closely related concept of self-efficacy, or the belief in one’s ability to perform a specific behavior or skill 9. in the healthcare field, providers who have higher self-efficacy regarding their clinical reasoning and communication skills may be more likely to engage in discussions regarding patients’ concerns 9,11. moreover, uncertainty and lower levels of clinician confidence may increase patients’ anxieties while higher levels of confidence may facilitate, trust, comfort, and overall rapport 8,12. thus, confidence has the potential to have profound impacts on the patient-physician relationship 8,9,11. nevisense (scibase, sweden) is an fdacleared and ce-marked device that measures electrical impedance spectroscopy (eis) in skin lesions to aid in biopsy decision-making for lesions suspicious for melanoma. the device reports a score of 0-10, with low scores (≤3) having a 99% negative predictive value for melanoma, and scores >3 having a sensitivity of 96.6% to diagnose melanoma in appropriately selected lesions 13. the addition of eis scores to clinical images resulted in more accurate biopsy decisionmaking by clinicians in survey studies.14-16. to date, however, the impact of eis scores on clinician confidence in diagnosing lesions as benign or malignant remains unknown. in addition, there have not been studies examining the change in diagnostic accuracy among clinicians first presented with dermoscopic images in addition to clinical images, prior to learning the eis score. we conducted a pilot study to evaluate whether the addition of an eis score to clinical and dermoscopic images increases diagnostic confidence, sensitivity, specificity and accuracy for the diagnosis of melanoma and severely dysplastic nevi using a set of images with corresponding eis scores and histopathology results. we also compared the differential impact of eis scores on the performance of novice diagnosticians (i.e., medical students) and pigmented lesion specialist dermatologists. in november 2020, three pigmented lesions specialists and three 4th year medical students with 4-12 months of dermoscopy experience from nyu grossman school of medicine were invited to complete an online survey to evaluate 34 melanocytic lesions suspicious for melanoma. the study and waiver of consent were approved by the nyu langone health institutional review board. cases were provided by scibase for training for a separate skin cancer diagnostic clinical trial. the selection of cases by scibase was intended for training purposes, and was based on the following two parameters: 1) adequate image quality for both clinical and dermoscopic images; and 2) atypical lesions that could be of concern to a clinician and benefit from additional information when making the decision to biopsy or not (figure 1). for each lesion, participants were provided the clinical history, and clinical and dermoscopic images. they were asked for their diagnosis, recommendation to biopsy or not, and level of confidence in classifying methods skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 22 a lesion as benign or malignant using a fivepoint scale (1 = not very confident, 2 = somewhat not confident, 3 = neutral, 4 = somewhat confident and 5 = very confident). next, participants were provided with the eis score and a clinical reference guide with positive and negative predictive values (figure 2) 13. they were again asked the same set of questions regarding diagnosis, recommendation to biopsy (or not), and confidence level. participants learned the histopathology result of each lesion after completing all the evaluation steps. lesions were presented in a random order. accuracy was defined as correctly diagnosing a lesion as “nevus” or “melanoma/severe dysplastic nevus” per histopathology. mean levels of confidence were calculated for all evaluations as well as for evaluations with accurate diagnoses only. medians, quartiles, and ranges of levels of confidence were calculated for each histopathologic category (common melanocytic nevi, dysplastic nevi, and melanoma). diagnostic confidence, sensitivity, specificity, and accuracy 17,18 between the evaluations with and without eis score were compared using paired ttests. all statistical analyses were performed for all evaluators combined as well as students only and dermatologists only. statistical analysis was performed using spss software (ibm inc. armonk, ny). all 34 lesions were evaluated by the six evaluators for a total of 204 evaluations. of the 6 common melanocytic nevi, 5 had an eis score ≤3 while 1 had an eis score of 4. for the 17 dysplastic nevi, the eis score was ≤3 for 8 lesions and ≥4 for the remaining 9. the eis scores for all 11 melanomas were ≥4 (table 1). mean confidence increased for 29/34 (85%) lesions, did not change for 3/34 (9%) lesions, and decreased for 2/34 (6%) lesions. of the lesions with increases in mean confidence, 26/29 (90%) were diagnosed correctly by >4 evaluators, and 2/29 (7%) by 2-3 evaluators. in addition, one mild to moderately dysplastic nevus with an eis score of 6 (lesion number 11) was inaccurately diagnosed as a melanoma by all evaluators, with or without the eis score. of the two lesions for which confidence decreased, one was a mild-moderate dysplastic nevus with an eis score of 4 (lesion number 15). it was diagnosed correctly by 2 students after viewing the eis score, and by one student with or without the eis score. it was incorrectly diagnosed as a melanoma with or without the eis score by all 3 pigmented lesions specialists. the second lesion for which confidence decreased was a severely dysplastic nevus with an eis score of 4 (lesion number 17). without eis it was accurately diagnosed by one student and one pigmented lesions specialist; with eis it was accurately diagnosed by two of three students, and all three pigmented lesions specialists albeit with less confidence (table 1). when grouping lesions by histopathologic category (common melanocytic nevi, dysplastic nevi, and melanomas), there were significant increases in mean confidence in the correct diagnosis across all three categories for both students and pigmented lesions specialists (figure 3). specifically, the mean diagnostic confidence for the diagnosis of common melanocytic nevi rose from 2.86 to 4.06 (p<.001) for students, and 3.07 to 4.20 (p=.005) for pigmented lesions specialists. similarly, the mean diagnostic results skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 23 figure 1. a) clinical and b) dermoscopic images of a mildly dysplastic nevus with an electrical impedance spectroscopy score of 2 from the training set used for this study (lesion number 9) figure 2. clinical reference guide indicating positive and negative predictive values of electrical impedance spectroscopy scores figure 3. box plot of mean diagnostic confidence for accurately diagnosed lesions in evaluations with images alone (green) and images plus electrical impedance spectroscopy (eis) score (blue) by histopathologic category. shading of boxes corresponds to quartiles. boxes with a single color indicate that the median did not differ from either the first or third quartile skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 24 confidence for the diagnosis of dysplastic nevi increased from 3.00 to 4.17 (p<.001) for students, and 3.32 to 3.81 (p = .003) for pigmented lesions specialists. finally, regarding melanoma, the mean diagnostic confidence rose from 3.83 to 4.59 (p<.001) for students, and 3.94 to 4.46 (p= .004) for pigmented lesions specialists. there were no statistically significant increases in confidence among lesion that were incorrectly diagnosed. mean diagnostic accuracy increased from 74% to 86% (p = .005) for all participants combined, and from 75% to 86% (p = .03) for students. the increase for dermatologists trended towards significance, increasing from 73% to 85% (p = .13). across all 6 evaluators, the addition of eis scores increased mean biopsy sensitivity for melanoma/severe dysplastic nevi from 70% to 84% (p = .014). there was a trend towards increased specificity, from 62% to 69% (p=0.06). for students, the biopsy sensitivity increased from 59% to 80% (p = .03); and there was a trend towards increased specificity from 67% to 75% (p=0.06). for the pigmented lesion specialists, the increases in sensitivity and specificity did not reach statistical significance (table 2). though it was not the primary objective when developing the training material, the sensitivity of eis for diagnosis of melanoma in the selected cases (100%) did not differ greatly from the sensitivity reported in the pivotal validation study for nevisense (97%). however, the specificity of eis for the cases in the training set (69%) was considerably higher than that of the pivotal study (34.4%) 13. study participants were unaware of these statistics prior to the study. although the performance of eis scores as a diagnostic aid in the management of skin lesions suspicious for melanoma has been previously demonstrated, its impact on clinician confidence in their biopsy decisions has not been described. in this pilot study, we found that the addition of eis scores to clinical and dermoscopic images significantly increased mean confidence in the correct diagnosis of common, dysplastic, and malignant melanocytic neoplasms for both students and pigmented lesions specialists. also, the addition of eis scores to clinical and dermoscopic images significantly increased diagnostic accuracy and biopsy sensitivity of suspicious melanocytic lesions among medical students. eis scores elevated the biopsy sensitivity of students close to that of dermatologists with images alone, suggesting particular value of eis for novice diagnosticians. moreover, this improvement in diagnostic accuracy among medical students is consistent with recent studies where the addition of eis scores to clinical images alone increased diagnostic accuracy for novice diagnosticians, including trainees and midlevel practitioners 14-16. among the pigmented lesions specialists, the addition of an eis score resulted in a trend toward improved accuracy of diagnosis, but it did not reach statistical significance. there are several possible explanations for this observation including pigmented lesions specialists depending more heavily on dermoscopy compared to the eis score since they had no prior experience integrating these scores into their decisionmaking discussion skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 25 table 1. mean diagnostic confidence in evaluations with images only and images plus eis score a negative predictive values (npv) and positive predictive values (ppv) of being melanoma: 0-3 = 99% npv, 4 = 7% ppv, 5 = 10% ppv, 6 = 22% ppv, 7 = 32% ppv, 8 = 45% ppv, 9 = 52% ppv, 10 = 61% ppv13 abbreviations: dn, dysplatic nevus students (n = 3) dermatologists (n = 3) combined (n = 6) histopathologic diagnosis eis score a images only with eis score pvalu e images only with eis score pvalue images only with eis score pvalue n with correct diagnosis common melanocytic nevi (all) 2.72 3.78 .001 3.00 4.06 .002 2.86 3.92 <.001 1. common melanocytic nevus 3 2.67 3.67 .23 2.67 3.67 .23 2.67 3.67 0.04 5 2. common melanocytic nevus 2 3.00 4.67 .13 3.33 4.33 .23 3.17 4.50 0.03 6 3. common melanocytic nevus 4 2.00 2.67 .18 2.67 3.33 .18 2.33 3.00 0.03 2 4. common melanocytic nevus 3 2.33 4.00 .04 3.00 4.33 .27 2.67 4.17 0.02 6 5. common melanocytic nevus 1 4.00 3.67 .74 4.33 5.00 .18 4.17 4.33 0.74 6 6. common melanocytic nevus 1 2.33 4.00 .04 2.00 3.67 .37 2.17 3.83 0.05 6 dysplastic/atypical nevi (all) 3.16 4.20 <.00 1 3.39 3.80 .005 3.27 4.00 <.001 7. dn mild 1 4.33 5 0.42 4.33 4.67 0.42 4.33 4.83 0.2 6 8. dn mild 3 3 4.33 0.27 2.67 4 0.06 2.83 4.17 0.03 6 9. dn mild 2 2.33 4 0.13 3 4.33 0.06 2.67 4.17 0.007 6 10. dn mild/moderate 3 2.67 4.33 0.13 3.67 4.33 0.18 3.17 4.33 0.03 6 11. dn mild/moderate 6 4 4.67 0.18 4 4.67 0.18 4 4.67 0.03 0 12. dn mild/moderate 6 2.67 4 0.42 2.67 3.33 0.18 2.67 3.67 0.18 4 13. dn mild/moderate 1 3.33 4.33 0.23 4 4.67 0.42 3.67 4.5 0.09 6 14. dn mild/moderate 5 3.67 3.67 >.99 2.67 2.67 >.99 3.17 3.17 >.99 4 15. dn mild/moderate 4 3.67 3.33 0.42 3.67 3.67 >.99 3.67 3.5 0.61 3 16. dn mild/moderate 3 3 4.33 0.06 3.33 3 0.84 3.17 3.67 0.54 5 17. dn severe 4 3.33 3.67 0.74 4 2.67 0.06 3.67 3.17 0.42 5 18. dn severe 3 3.33 4.67 0.27 4 4.67 0.18 3.67 4.67 0.08 3 19. dn severe 5 3 4.67 0.13 3 3.67 0.42 3 4.17 0.06 6 20. dn severe 4 3 3.67 0.53 2.67 3.33 0.18 2.83 3.5 0.18 6 21. dn severe 3 3 3.67 0.53 2.67 2.67 >.99 2.83 3.17 0.53 6 22. dn severe 7 2.23 4 0.04 3 3.67 0.18 2.67 3.83 0.01 6 23. dn severe 9 3 5 0.07 4.33 4.67 0.42 3.67 4.83 0.06 6 melanoma (all) 3.86 4.67 <.00 1 3.92 4.47 .001 3.89 4.57 <.001 24. melanoma – in situ 6 3 4 0.23 2.33 4.33 0.07 2.67 4.17 0.02 4 25. melanoma – in situ 6 3.33 4.33 0.23 2.33 3.67 0.06 2.83 4 0.01 5 26. melanoma – in situ 6 4.33 4.67 0.42 3.33 3.33 >.99 3.83 4 0.61 4 27. melanoma – in situ 7 4.67 5 0.42 4.67 4.67 >.99 4.67 4.83 0.61 6 28. melanoma – in situ 8 5 5 5 5 5 5 6 29. melanoma – in situ 8 3.67 4 0.42 4.67 4.33 0.42 4 4.33 0.18 6 30. melanoma – in situ 10 3 5 0.07 4.33 4.67 0.42 3.67 4.83 0.06 6 31. melanoma – in situ 8 2 4 0.07 3.33 4 0.18 2.67 4 0.03 5 32. melanoma – t1 9 4.33 5 0.18 3.67 4.67 0.42 4 4.83 0.14 6 33. melanoma – t1 10 5 5 5 5 5 5 6 34. melanoma – t1b 7 5 5 5 5 5 5 6 skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 26 table 2. sensitivity, specificity and accuracy for evaluations with images only and images plus electrical impedance spectroscopy score a biopsy specificities were positively skewed for students, resulting in greater mean specificities for students compared to dermatologists these findings build on a previous report that found that dermoscopy increased diagnostic confidence for common nevi and melanomas, but not for dysplastic nevi when compared to clinical images alone 8. since dysplastic nevi are often equivocal on dermoscopy, eis may be especially useful for the diagnosis of these lesions. the addition of eis scores to trained clinical and dermoscopic evaluation may allow dermatologists to exhibit greater confidence regarding dermoscopically equivocal lesions and provide prompt explanations (i.e. affective and cognitive reassurance 19,20) to alleviate patients’ anxieties. this would be particularly helpful in clinically atypical, low scoring lesions where dermatologists can more confidently inform patients of the benign nature of these lesions. eis scores may also foster confidence and learning among novice diagnosticians as they refine their diagnostic skills throughout their dermatologic training. there are several limitations to this pilot study. most importantly, we recognize the small sample size of participants in this study. the number of participants was intentionally kept small since the nevisense device is not available in our center at this time for routine clinical use, and we did not want to inadvertently promote its use among trainees and other faculty members. another important consideration is that in clinical settings many diagnostically equivocal pigmented lesions may be non-melanocytic (e.g. atypical solar lentigines). these lesions are known to have elevated eis scores, so applying eis measurement to a clinically suspicious, yet non-melanocytic lesion has a high chance of a false positive test result. thus, clinicians have to make the additional decision of whether or not it would be appropriate to utilize eis on a particular lesion, a step that was not included in this study. moreover, the stakes of deciding whether or not to biopsy a lesion are higher in a clinical setting than in the context of a survey study. additional limitations include the small number of lesions included and the potential for selection bias in the choice of lesions provided by scibase. as noted above, the specificity of nevisense for the diagnosis of melanoma/severely dysplastic nevus was higher than that reported in the pivotal clinical trial. in this pilot study, we tested the concept that integrating eis scores with clinical and dermoscopic images would significantly increase diagnostic confidence for both students and dermatologists in the fourth-year medical students (n=3) pigmented lesion expert dermatologists (n=3) combined (n=6) images only with eis score pvalue images only with eis score pvalue images only with eis score pvalue biopsy sensitivity 59.3 79.6 .03 81.5 88.9 .18 70.4 84.3 .01 biopsy specificity a 66.7 75.0 .06 56.3 62.5 .42 61.5 68.8 .06 accuracy 75.4 86.3 .03 72.5 85.3 .13 74.0 85.8 .005 conclusion skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 27 evaluation of melanocytic nevi and melanoma. despite the small sample sizes, we did find statistically significant improvements in diagnostic confidence and accuracy among the students and pigmented lesions specialist dermatologists. additional larger studies in real-world clinical settings are needed to more fully examine the role of eis in providing patients with greater reassurance when their clinically atypical nevi are being evaluated, and facilitating clinical decision-making. conflict of interest disclosures: the authors have no financial conflicts of interest to declare. all authors except for lf are or were team members on a separate skin cancer diagnostic study utilizing nevisense. funding: none corresponding author: david polsky, md, phd the ronald o. perelman department of dermatology nyu grossman school of medicine nyu langone health 522 first avenue, smilow 404 new york, ny 10016 david.polsky@nyulangone.org references: 1. marghoob aa, swindle ld, moricz czm, et al. instruments and new technologies for the in vivo diagnosis of melanoma. journal of the american academy of dermatology. 2003;49(5):777-797. 2. fried l, tan a, bajaj s, liebman tn, polsky d, stein ja. technological advances for the detection of melanoma: advances in molecular techniques. journal of the american academy of dermatology. 2020;83(4):996-1004. 3. carli p, de giorgi v, crocetti e, et al. improvement of malignant/benign ratio in excised melanocytic lesions in the 'dermoscopy era': a retrospective study 1997-2001. the british journal of dermatology. 2004;150(4):687-692. 4. fried l, tan a, bajaj s, liebman tn, polsky d, stein ja. technological advances for the detection of melanoma: advances in diagnostic techniques. journal of the american academy of dermatology. 2020;83(4):983-992. 5. kittler h, pehamberger h, wolff k, binder m. diagnostic accuracy of dermoscopy. the lancet oncology. 2002;3(3):159-165. 6. menzies sw, emery j, staples m, et al. impact of dermoscopy and short-term sequential digital dermoscopy imaging for the management of pigmented lesions in primary care: a sequential intervention trial. british journal of dermatology. 2009;161(6):12701277. 7. wolner zj, yélamos o, liopyris k, rogers t, marchetti ma, marghoob aa. enhancing skin cancer diagnosis with dermoscopy. dermatologic clinics. 2017;35(4):417-437. 8. benvenuto-andrade c, dusza sw, hay jl, et al. level of confidence in diagnosis: clinical examination versus dermoscopy examination. dermatologic surgery : official publication for american society for dermatologic surgery [et al]. 2006;32(5):738744. 9. hecimovich md, volet se. importance of building confidence in patient communication and clinical skills among chiropractic students. the journal of chiropractic education. 2009;23(2):151-164. 10. baranski jv, petrusic wm. probing the locus of confidence judgments: experiments on the time to determine confidence. journal of experimental psychology: human perception and performance. 1998;24(3):929-945. 11. parle m, maguire p, heaven c. the development of a training model to improve health professionals' skills, self-efficacy and outcome expectancies when communicating with cancer patients. social science & medicine. 1997;44(2):231-240. 12. giroldi e, veldhuijzen w, mannaerts a, van der weijden t, bareman f, van der vleuten c. “doctor, please tell me it’s nothing serious”: an exploration of patients’ worrying and reassuring cognitions using stimulated recall interviews. bmc fam pract. 2014;15(1):73. 13. malvehy j, hauschild a, curiellewandrowski c, et al. clinical performance of the nevisense system in cutaneous melanoma detection: an international, multicentre, prospective and blinded clinical trial on efficacy and safety. br j dermatol. 2014;171(5):1099-1107. 14. svoboda rm, prado g, mirsky rs, rigel ds. assessment of clinician accuracy for diagnosing melanoma on the basis of mailto:david.polsky@nyulangone.org skin january 2022 volume 6 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 28 electrical impedance spectroscopy score plus morphology versus lesion morphology alone. journal of the american academy of dermatology. 2019;80(1):285-287. 15. litchman gh, teplitz rw, marson j, rigel ds. impact of electrical impedance spectroscopy on dermatologists’ numberneeded-to-biopsy metric and biopsy decisions for pigmented skin lesions. journal of the american academy of dermatology. 2020. 16. litchman gh, marson, j. w., svoboda, r. m., & rigel, d. s. integrating electrical impedance spectroscopy into clinical decisions for pigmented skin lesions improves diagnostic accuracy: a multitiered study. skin the journal of cutaneous medicine. 2020;4(5):424-430. 17. baratloo a, hosseini m, negida a, el ashal g. part 1: simple definition and calculation of accuracy, sensitivity and specificity. emergency (tehran, iran). 2015;3(2):48-49. 18. parikh r, mathai a, parikh s, chandra sekhar g, thomas r. understanding and using sensitivity, specificity and predictive values. indian journal of ophthalmology. 2008;56(1):45-50. 19. dang bn, westbrook ra, njue sm, giordano tp. building trust and rapport early in the new doctor-patient relationship: a longitudinal qualitative study. bmc medical education. 2017;17(1):32. 20. holt n, pincus t. developing and testing a measure of consultation-based reassurance for people with low back pain in primary care: a cross-sectional study. bmc musculoskeletal disorders. 2016;17. skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 238 brief article treatment-resistant pemphigoid following sars-cov-2 vaccination stefanie altmann, do1, dominique jacobs, bs2, thomas brown, do1, preetha kamath, md1, karthik krishnamurthy, do1 1 hca healthcare/mercer university school of medicine/orange park medical center, orange park, fl 2 philadelphia college of osteopathic medicine, philadelphia, pa on december 18, 2020, modernatx received emergency use authorization from the food and drug administration to release the mrna-1273 vaccine in order to reduce the severity of sars-cov-2 infection.1 as the sars-cov-2 vaccinated population increases, there have been increased reports of cutaneous reactions, the most common being a delayed large local reaction.1 additionally, there have been fewer reports of systemic cutaneous reactions, including but not limited to urticaria and morbilliform exanthems.1 a systematic review published in april 2021 reported no association between covid-19 vaccination and autoimmune bullous disease (aibd).2 however, there have been recent reports of new-onset subepidermal blistering disease following sars-cov-2 mrna vaccination.3 we report a case of treatment-resistant bullous pemphigoid in a 70-year-old male following the second dose of the mrna-1273 vaccine. a 70-year-old male with a past medical history of hypertension, hyperlipidemia, and gastroesophageal reflux disease presented to the clinic with a 2-month history of new lesions on his extremities and trunk. the patient noted the eruption began one week after he had received his second dose of the mrna-1273 vaccine. he denied oral lesions or systemic symptoms, and he described the lesions as burning and progressively spreading. on exam, several large, geometric, eroded plaques and bullae with surrounding erythema were noted on his right distal leg (figure 1, a). smaller, similar lesions were also noted on the abdomen and bilateral arms (figure 1, b). 4-mm abstract as the sars-cov-2 vaccinated population increases, there have been many reports of vaccineinduced cutaneous reactions but scarce information on vaccine-induced autoimmune bullous disease. vaccinations have been associated with the unmasking or development of autoimmune bullous disease; however, there is little data on sars-cov-2, specifically. we report a rare case of new-onset pemphigoid in a 70-year-old male following the second dose of the mrna-1273 vaccine. the patient’s disease has been refractory to treatment, thus the underlying pathophysiology in vaccine-induced pemphigoid is likely unique, and further investigation into this pathophysiology is warranted. introduction case report skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 239 punch biopsies were performed for further evaluation, and the patient was started on low-dose prednisone. figure 1. pemphigoidclinical images on the day of initial presentation a) several large, geometric, eroded plaques and bullae with surrounding erythema were noted on his right distal leg b) eroded inflammatory plaques on the left arm. histopathology revealed a subepidermal blister with eosinophils (figure 2, a and b). direct immunofluorescence showed linear deposition of igg and c3 along the basement membrane zone. these findings supported a diagnosis of bullous pemphigoid (bp). two weeks later the patient developed new oral lesions. salt-split skin (sss) was performed on the initial specimen, which demonstrated linear igg localizing predominantly to the epidermal side of the blister, labeling the dermal side of the blister to a lesser extent (figure 3, a and b), favoring bp. serum basement membrane zone and intercellular skin autoantibodies were negative at this time. the patient’s medication list was reviewed and was unremarkable. treatment was initiated with a combination of high-dose oral prednisone (1 mg/kg/day), doxycycline 100mg twice daily, nicotinamide 500mg three times daily, and triamcinolone 0.1% cream, combined with gentamicin ointment under occlusion. the patient had persistent oral and cutaneous lesions at 2-week follow-up. therefore, dapsone 12.5mg daily was added to his regimen, which was titrated up to 50mg daily over 2 months. during this time, prednisone was tapered off. the patient had minimal improvement with this regimen and continued to develop breakthrough lesions. due to the inadequate response to treatment, biopsy was repeated. dif was positive for thin wavy deposition of igg and slightly weaker c3 along both the dermal (“n” serrated pattern) as well as the epidermal side of the salt-split (nacl 1 m x 24 hs) basement membrane zone. these findings confirmed an igg subepithelial blistering disease. based on clinicalpathological correlation, bp, or anti-laminin gamma-1 (p200) pemphigoid were considered. serum enzyme-linked immunosorbent assay (elisa) for antibp180 and anti-bp230 was then performed. anti-bp180 antibody levels were elevated (22 u/ml; reference value, < 14), thus a diagnosis of bp was favored. dapsone was discontinued and mycophenolate mofetil was initiated, titrating up to 1g twice daily. several studies suggest that vaccinations may be associated with unmasking or the development of autoimmune disorders.4 the pathophysiology remains unclear, however molecular mimicry and bystander activation are reported as possible mechanisms.4 kasperkiewicz et. al discusses 28 patients from 1995 to 2021 diagnosed with aibd occurring 1-day to 3-months status-post vaccination.2 these vaccinations were most commonly for influenza, tetanus, diphtheria, hepatitis, and varicella-zoster, with no discussion skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 240 figure 2. pemphigoidhistopathology of lesion tissue. a and b, histopathologic image demonstrating a subepidermal blister with eosinophils. (h&e; original magnification: a) ×100; b) ×200) figure 3. pemphigoidsalt-split skin (nacl 1 m x 24 hs) demonstrating linear igg localizing predominantly to the epidermal side of the blister, labeling the dermal side of the blister to a lesser extent (original magnification: a) x100; b) x400) reports of sars-cov-2.2 of the biopsyproven reports of sars-cov-2 vaccineassociated bp in a letter to the editor, 75% of these patients exhibited symptoms 1-21 days after the second dose,3 which is consistent with our patient’s timeline. in these cases, 7 out of 12 patients had resolution or improvement of lesions at a median of 3 weeks after treatment with topical and systemic steroids, doxycycline, and nicotinamide.3 of the 5 patients with ongoing disease, tomayko proposed the possibility of a different pathophysiology.3 our patient had persistent disease despite treatment, and thus a different pathophysiology should be considered. interestingly, our patient had oral mucosal lesions in the setting of both dermal and epidermal staining on sss. this could suggest bp with recognition of more distal epitopes near the non-collagenous domain of bp180. another possible explanation is that our patient has anti-p200 pemphigoid with epitope spreading and the additional skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 241 targeting of bp180. further testing for antip200 pemphigoid was not pursued in our case, however, this could be a future consideration. thus, the underlying pathophysiology in vaccine-induced pemphigoid is likely unique, and further investigation is warranted. the authors suspect this to be a true vaccine-triggered case of pemphigoid. bp affects the elderly and is typically seen in patients 70 years of age and older.5 considering our patient is a 70-year-old male, his initial presentation following sars-cov-2 vaccination could represent coincidental unmasking of subclinical bp, although the authors feel this is less likely given the timeline, refractory course, and similar reports of bp after vaccination.3 additional reports discuss inconclusive or bp-negative, bullous-like eruptions related to sars-cov-2 vaccination.3,6 this is due to either patient loss to follow-up or negative direct immunofluorescence.3 additionally, new-onset bp has been reported in patients with acute sars-cov-2 infection.7-8 our patient was not tested for sars-cov-2 at the time of diagnosis, as he was asymptomatic and had just completed the mrna vaccine series. therefore, the possibility of sars-cov-2 infection was not ruled out, but highly unlikely. the sars-cov-2 vaccination is the first approved use of an mrna vaccine in humans and a more complete understanding of potential off-course immunostimulatory properties will require more investigation.9 it is important to be aware that pemphigoid and pemphigoid-like diseases may develop after sars-cov-2 vaccination. however, given the significant health risks of sars-cov-2 infection and the rarity of these events, clinicians should continue to encourage full vaccination. conflict of interest disclosures: none funding: none corresponding author: stefanie altmann do, orange park medical center department of dermatology 2001 kingsley ave, orange park, fl 32073 phone: (904) 639-8500 email: stefanie.altmann@hcahealthcare.com references: 1. mcmahon de, amerson e, rosenbach m, et al. cutaneous reactions reported after moderna and pfizer covid-19 vaccination: a registrybased study of 414 cases. journal of the american academy of dermatology. 2021;85(1):46-55. https://dx.doi.org/10.1016/j.jaad.2021.03.092. doi: 10.1016/j.jaad.2021.03.092. 2. kasperkiewicz m, woodley dt. association between vaccination and autoimmune bullous diseases: a systematic review. j am acad dermatol. 2021. accessed aug 20, 2021. doi: 10.1016/j.jaad.2021.04.061. 3. tomayko mm, damsky w, fathy r, et al. subepidermal blistering eruptions, including bullous pemphigoid, following covid-19 vaccination. j allergy clin immunol. 2021. doi: s0091-6749(21)01054-x [pii]. 4. vadalà m, poddighe d, laurino c, palmieri b. vaccination and autoimmune diseases: is prevention of adverse health effects on the horizon? epma j. 2017;8(3):295-311. accessed aug 21, 2021. doi: 10.1007/s13167-017-0101-y. 5. kridin k, ludwig rj. the growing incidence of bullous pemphigoid: overview and potential explanations. front med (lausanne). 2018;5:220. accessed aug 21, 2021. doi: 10.3389/fmed.2018.00220. 6. kong j, cuevas-castillo f, nassar m, et al. bullous drug eruption after second dose of mrna-1273 (moderna) covid-19 vaccine: case report. j infect public health. 2021. accessed aug 12, 2021. doi: 10.1016/j.jiph.2021.06.021. 7. kim a, khan m, lin a, wang h, siegel l, rozenberg s. new bullous eruptions in a covid-19 positive patient in an intensive care unit. j of skin. 2021;5(3):278-282. https://jofskin.org. accessed aug 12, 2021. doi: conclusion https://jofskin.org/ skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 242 10.25251/skin.5.3.9. 8. olson n, eckhardt d, delano a. new-onset bullous pemphigoid in a covid-19 patient. case rep dermatol med. 2021;2021:5575111. doi: 10.1155/2021/5575111 [doi]. 9. pardi n, hogan mj, porter fw, weissman d. mrna vaccines — a new era in vaccinology. nature reviews. drug discovery. 2018;17(4):261-279. https://www.ncbi.nlm.nih.gov/pubmed/29326426 . doi: 10.1038/nrd.2017.243. https://www.ncbi.nlm.nih.gov/pubmed/29326426 https://www.ncbi.nlm.nih.gov/pubmed/29326426 skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 546 short communication psoriasiform eruption in an immunocompromised neurosyphilis patient olivia lawson, bs1, collins langley, md1, michael davis, md2,3 1 college of medicine, university of tennessee health science center, memphis, tn 2 college of medicine, university of tennessee health science center, chattanooga, tn 3 department of internal medicine, university of tennessee health science center, chattanooga, tn the rash of syphilis may take on a number of different morphologies, especially in the immunocompromised. here we present an immunocompromised man with tertiary syphilis and a psoriatic eruption of his palms and soles. a 38-year-old male presented with a fiveweek history of a mildly pruritic, diffuse papulosquamous rash on his chest, back, and arms (figure 1), and a thick scaling rash with fissures on his palms and soles (figure 2). he additionally had a ten-day history of progressive painful bilateral vision loss and headache. he had a history of untreated hiv with a cd4 count of 599 cells/mm3 and tested positive for hepatitis b surface antigen during his admission. a positive serum rpr and a positive csf vdrl confirmed the diagnosis of neurosyphilis, and he was started on a 10day course of iv penicillin g. he was initially diagnosed with presumptive cmv retinitis due to his history of immunosuppression, so oral valganciclovir and intravitreal ganciclovir and foscarnet were begun. however, anterior compartment eye biopsies were negative for cmv, and he was diagnosed with ocular syphilis. over the course of his 10-day admission his vision slowly improved and was almost completely regained by the time of his discharge. the rash on his palms and soles was painful, and the fissures bled when he walked. topical emollients provided mild relief. the lesions on his face, head, chest, back, and arms slowly improved with treatment, but the rash on his palms and soles remained severe even at discharge. fortunately, this patient had a phenomenal outcome. one week after his discharge he was feeling very well and was seeing gradual improvement of his palms and soles. he was scheduled to follow up for outpatient hiv and hepatitis treatment. introduction case report skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 547 figure 1. diffuse papulosquamous rash on the upper back and shoulders figure 2. thick, scaling, psoriasiform rash on the palms (a) and soles (b). fissures present on bilateral feet. the spirochete treponema pallidum may cause a range of cutaneous manifestations so broad, that syphilis has been called “the great imitator”. the early rash of secondary syphilis classically presents as localized or diffuse macules or papules. they may vary in color, but are most often pale pink on lighter skin or violaceous on darker skin.1 later in the disease course the rash is primarily papulosquamous and may affect the extremities, trunk, palms, and soles.2 however, up to 12 distinct lesion classifications have been reported among the cutaneous manifestations of syphilis.1,2 with so many clinical presentations, syphilis is often mistaken for any number of the more common diagnoses it resembles, including pityriasis rosea and lichen planus. atypical presentations of the rash have been reported most frequently in patients with simultaneous hiv infection.2 if this patient had presented without neurologic or systemic symptoms, he could have easily been misdiagnosed with palmoplantar psoriasis. the psoriasiform presentation of syphilis was first reported in the literature in 1885 when guibout christened it syphilide psoriasiforme. in 1906, fournier then described the predilection for the medial aspect of the sole, as well as the fissuring, associated with this variant.3 today, there are a few case reports of this presentation. however, we believe that the patient presented here is unique among the reports due to the striking extent of fissuring and thick scale present across the entire plantar and palmar surfaces. conflict of interest disclosures: none funding: none corresponding author: olivia lawson, bs uthsc college of medicine 910 madison ave suite 1031 memphis, tn 38163 phone: (276) 701-3610 email: olawson3@uthsc.edu references: discussion skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 548 1. baughn re, musher dm. secondary syphilitic lesions. clinical microbiology reviews. 2005;18(1):205-216. doi:10.1128/cmr.18.1.205216.2005 2. balagula y, mattei pl, wisco oj, erdag g, chien al. the great imitator revisited: the spectrum of atypical cutaneous manifestations of secondary syphilis. international journal of dermatology. 2014;53(12):1434-1441. doi:10.1111/ijd.12518 3. martins cj, lima rb, eyer-silva w de a, et al. secondary syphilis presenting as syphilide psoriasiforme: lessons from the older syphilology literature. revista do instituto de medicina tropical de sao paulo. 2020;62. doi:10.1590/s1678-9946202062021 powerpoint presentation wake forest university school of medicine is the academic core of atrium health. introduction • psoriasis is a common inflammatory skin condition that varies in severity • most patients have limited disease amenable to topical treatment, however poor treatment adherence limits efficacy1,2,3 • purpose: to assess patients’ psoriasis treatment experience, expectations, and preferences methods • the national psoriasis foundation conducted a survey in march 2022 that recruited 411 participants • inclusion criteria: o psoriasis diagnosed by a healthcare provider o active disease within six months to one year of the survey collection o commercial insurance alyssa curcio1, christina kontzias1 steven r. feldman1 1 wake forest school of medicine, department of dermatology improving patient acceptability and adherence in psoriasis treatment results • most participants (83.9%) self-reported moderate psoriasis • symptoms reported the most bothersome were scaly appearance (78.8%), bleeding/oozing (60%), itch (55%), and flaking (37.4%) • most participants (76%) reported using topical therapy at least once weekly • nearly 80% of participants said they would allow two weeks for a medication to become effective before considering discontinuation • if a topical medication caused a reaction, more than 40% of patients said they would call another dermatologist • if participants did not like a topical treatment's formulation, most (74.7%) said they would continue to use the medication for a week before discontinuation conclusion • topical treatments continue to be a mainstay of psoriasis treatment • patients expect to see rapid improvement with topical treatment; otherwise, they report they will discontinue treatment • the characteristics of psoriasis treatment vehicles also affects patients’ reported willingness to use treatment and may be an important consideration in treatment planning refrences 1. savary j, ortonne jp, aractingi s. the right dose in the right place: an overview of current prescription, instruction and application modalities for topical psoriasis treatments. j eur acad dermatol venereol. 2005 nov;19 suppl 3:14-7. doi: 10.1111/j.1468 3083.2005.01333.x. pmid: 16274407. 2. feldman sr, horn ej, balkrishnan r, basra mk, finlay ay, mccoy d, menter a, van de kerkhof pc; international psoriasis council. psoriasis: improving adherence to topical therapy. j am acad dermatol. 2008 dec;59(6):1009-16. doi: 10.1016/j.jaad.2008.08.028. epub 2008 oct 2. pmid: 18835062. 3. florek ag, wang cj, armstrong aw. treatment preferences and treatment satisfaction among psoriasis patients: a systematic review. arch dermatol res. 2018 may;310(4):271-319. doi: 10.1007/s00403-018-1808-x. epub 2018 feb 13. pmid:29442137. national psoriasis foundation survey questions 1. how would you describe your psoriasis? 2. how has your dermatologist categorized your psoriasis? 3. where do you have/had psoriasis plaques? 4. how frequently do you use topical prescriptions to treat your psoriasis plaques? 5. do you use prescription, over-the-counter medication, or both to treat your psoriasis? 6. other than topical medications, what other prescription-based treatment do you routinely use? 7. how quickly do you need to notice an improvement in your psoriasis due to a topical prescription medication before you assume it isn’t working and stop usings it? 8. which signs and symptom(s) of your psoriasis do you find most bothersome? 9. do you suffer from itch due to your psoriasis? 10. if you have itch, where does this affect you? 11. on a scale of 1-10, how would you rate the worst your itch has been in the last month? 12. which attributes are most important to you in a prescription treatment? 13. if you don’t like the product formulation prescribed, how long will you give it to see if it works? 14. if a topical prescription your dermatologist prescribed for you causes an unpleasant reaction or rash on your skin, what are you most likely to do? 15. of all the topical prescription treatments you’ve previously tried, which three formulations have you preferred? 16. if you have used a topical prescription treatment on your scalp, how easy was it to remove the medication from your hair? 17. if you can remember the brand names of any topical prescription products you’ve used, please list them. 227 205 192 163 117 92 69 58 41 40 28 application feel doesn’t stain fabric quick absorbtion not sticky/thick application ease no unpleasant smell non-greasy works quickly doesn’t sting or burn no adverse skin reaction once daily treatment number of survery participants topical treatment formulation preferences 75.7% 70.8% 48.7% 42.8% 31.2% 17.5% 16.5% 6.3% p e rc e n ta g e o f p s u rv e y p a rt ic ip a n ts topical treatment vehicle preferences incidence of cutaneous adverse events with pi3k-akt-mtor pathway inhibitors: a systematic review and network meta-analysis abdulhadi jfri1,2, rachel meltzer1,2, lauren guggina1,2 background phosphoinositide 3-kinase/akt mammalian target of rapamycin (pi3k-akt-mtor) pathway is an intracellular signaling pathway that plays a pivotal role in the cell cycle control. it is an important target in malignancies that include pi3k inhibitors that contain three classes (pan-class i, isoform-selective and dual pi3k/mtor inhibitors), akt inhibitors and mtor inhibitors. immune-mediated side effects are common with inhibitors of this pathway, but incidence of cutaneous adverse events is lacking. objective to investigate the incidence of cutaneous adverse events with pi3k-akt-mtor pathway inhibitors from randomized clinical trials. methods we performed a systematic review of the pubmed, cochrane central register, embase and clinical trial registries on september 9, 2021 on phase 2 or 3 randomized control trials (rcts) studying pi3k/akt/mtor inhibitors. data were extracted based on the preferred reporting items for systematic review and meta-analysis guidelines. network meta-analysis in frequentist framework using mantel-haenszel method (for sparse event data) was performed with r package “netmeta.” 1brigham and women’s hospital, harvard medical school, boston, usa. 2dana farber cancer institute, boston, usa. results a total of 134 publications were initially identified and 58 registered trials. there were a total of 43 relevant rcts examining 7 pi3k inhibitors, 4 akt inhibitors, 3 mtor inhibitors, conventional and placebo, with a cumulative sample size of 13,029 participants. test of inconsistency yielded statistical non-significance (q= 11.12, df= 6, p =0.08). compared with placebo and conventional treatments, pi3k inhibitors, mtor inhibitors and akt inhibitors were more likely to develop rashes among the intervention group (figure 1). largest effect sizes were seen for pi3k inhibitors (or = 4.46, 95% ci: 3.32 to 5.99), followed by akt inhibitors (or = 3.53, 95% ci: 2.08 to 5.98) and mtor inhibitors (or = 3.47, 95% ci= 2.79 to 4.32). conclusion this study provides incidence of cutaneous adverse events with pi3k inhibitors, akt inhibitors and mtor inhibitors. further studies to explore the predictive value of cutaneous adverse events on response to therapy and survival outcomes are warranted. references figure 1. pairwise comparisons presenting likelihood of development of cutaneous adverse events with pi3k-akt-mtor pathway inhibitors skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 326 original research electrosurgery and implantable electronic devices: a survey of current practices among cutaneous surgeons caroline r. morris, md1, eva a. hurst, md1 1department of internal medicine, division of dermatology, washington university, st louis, missouri abstract background: the use of electrosurgery within dermatology is widespread and the number of patients with an implantable electronic device (ied) is ever-increasing. adverse effects of performing electrosurgery on patients with ieds could pose a significant patient safety risk. there is a paucity of literature detailing guidelines for cutaneous surgeons regarding electrosurgery in ied patients. objective: to assess current practices and complications of cutaneous surgeons performing electrosurgery in ied patients. methods: an electronic survey was distributed to members of the american college of mohs micrographic surgery using redcap. data was collected between march 2019 and may 2019. results: the survey was sent to 1700 acms members with 178 responses received. the most commonly reported routine precautions included utilization of short bursts of current, avoidance of electrosurgery around the device, and use of minimal power/lowest effective settings. in total there were nine complications with an estimated 31 patients experiencing electromagnetic interference (emi) out of over 250,000 procedures. complications were more common in patients with a cardioverter-defibrillator than any other device (rr:4.74, ci:1.29-17.4). the use of true heat cautery and bipolar (two-tip electrode) were associated with the lowest rate of emi. whereas, electrocoagulation, electrosection, and monopolar (single-tip electrode) were more likely to cause emi (rr:3.62, 95% ci:1.82-7.19). conclusions: significant emi to ieds during routine cutaneous electrosurgery procedures is rare, however, there is a clear lack of recommendations. the use of bipolar forceps and electrocautery may be safer when electrosurgery is required. further investigation is required to develop guidelines for electrosurgery in ied patients. 2019 resident research competition – 3rd place skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 327 there is an ever-increasing number of patients with implantable electronic devices (ieds) as indications for a multitude of cardiac and neurologic diseases continues to expand. these ieds include implantable cardioverter-defibrillators, cardiac pacemakers, deep brain stimulators, cochlear implants, and stimulators of the spinal cord and other nerves. the use of electrosurgery within dermatology is widespread, therefore, encountering patients with an ied who present for an office-based procedure is becoming progressively common. malfunction of ieds has been reported during routine electrosurgical procedures due to electromagnetic interference (emi).1 thus, adverse effects due to performing electrosurgery on patients with ieds present a significant patient safety risk and prompts concern over what risks these patients are exposed to during cutaneous surgery and the precautions that need to be utilized. minimal literature exists concerning guidelines for cutaneous surgeons regarding electrosurgery in patients with ieds.2,3 the survey was developed through a process of expert review by five dermatologic surgeons. feedback was provided by subject matter experts and incorporated into the final version of the survey. institutional review board exemption was obtained through washington university school of medicine. the electronic survey (using redcap) was approved by the american college of mohs surgery (acms) executive committee and distributed by email to all registered acms members. the e-mail was sent to a total of approximately 1,700 recipients. reponses were collected from march 2019 to may 2019. all received responses were included and analyzed. baseline demographic factors and routine precautions were reported as frequency distributions and percent of the total. comparisons of complications stratified by device type were tested using pearson chisquared analysis. p-values of less than 0.05 were considered statistically significant. study data were collected and managed using redcap electronic data capture tools hosted at washington university in st. louis.4 all statistical analyses were conducted in sas software. an electronic survey was sent to approximately 1,700 recipients and a total of 178 responses were received with a response rate of 10.5%. the years in practice and practice setting of survey respondents are presented in table 1. of the responses, 49% (n=87) had been in practice 1-10 years, 23% (n=40) 11-20 years, 19% (n=33) 21-30 years, and 9% (n=16) for 30+ years. practice settings included 20% (n=35) in a university, 73% (n=128) in private practice, 4% (n=7) in a mixed practice setting, and 3% (n=6) in other. the majority of respondents had encountered the following implantable electronic devices at some point in their practice: cardioverterdefibrillator (99%), pacemaker (100%), cochlear implant (81%), deep brain stimulator (80%), spinal cord stimulator (72%), and nerve stimulator (55%) (see table 2). the estimated total number of patients treated with electrosurgery and the number of patients with an ied treated with electrosurgery over the previous five years reported by respondents is presented in introduction methods results skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 328 table 3. well over 250,000 procedures involving electrosurgery were reported. routinely implemented (>90%) precautions with use of electrosurgery in a patient with an ied are presented in table 4. the most common routine precautions, independent of ied type, were utilization of only short bursts of current (< 5 secs), avoidance of electrosurgery around the ied, and use of minimal power and lowest effective settings. intraoperative monitoring (blood pressure, heart rate), changing a pacemaker to a fixed rate mode, and preand post-operative ekg were the least commonly used precautions. identification of device, including location, type, manufacturer, programming parameters, or date of manufacture/implantation, had a significant association with decreased complication rate in patients with a cardioverterdefibrillator (p-value 0.0491) and spinal cord stimulator/nerve stimulator (p-value 0.040). deactivation of a device was associated with a decreased rate of complications in patients with a deep brain stimulator/cochlear implant (p-value 0.006). preand post-operative monitoring and avoidance of electrosurgery around the ied were associated with decreased complication rate in patients with a spinal cord stimulator/nerve stimulator (pvalue < 0.001 and 0.032, respectively). having staff trained in acls was associated with a decreased complication rate in patients with a deep brain stimulator/cochlear implant (p-value 0.013) and spinal cord stimulator/nerve stimulator (p-value 0.001). none of the other precautions were found to have a statistically significant association with decreased rate of complications by pearson chi-squared analysis. in total there were an estimated 31 patients who experienced emi of an ied with nine complications reported, which included firing of a cardioverter-defibrillator (n=5), arrhythmia/missed beats in a patient with a pacemaker (n=1), deactivation of a deep brain stimulator (n=1), hemi-body tetany in a patient with a deep brain stimulator (n=1), and deactivation of a spinal cord stimulator or nerve stimulator (n=1). complications were more commonly seen in patients with a cardioverter-defibrillator than any other device (rr:4.74, ci:1.29-17.4). the mean rate of emi due to electrosurgery in a patient with an ied was 0.96 (95% ci: 0-2.15) events per 1000 patients. the use of true heat cautery (n=1) and bipolar (two-tip electrode) (n=1) were reported with the lowest rate of emi. whereas, electrocoagulation (n=10), electrosection (n=8), and monopolar (singletip electrode) (n=9) were more commonly reported to cause emi than any other mode of electrosurgery (rr:3.62, 95% ci:1.827.19). skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 329 table 1. years in practice and practice setting of respondents. years in practice 1-10 11-20 21-30 30+ % (n) 49% (87) 23% (40) 19% (33) 9% (16) practice setting university private mixed other % (n) 20% (35) 73% (128) 4% (7) 3% (6) table 2. implantable electronic devices encountered by percentage of survey respondents. implantable electronic device % (n) cardioverter-defibrillator 99% (171) pacemaker 100% (172) cochlear implant 81% (132) dbs 80% (132) scs 72% (112) nerve stimulator 55% (84) table 3. total estimated number of patients treated with electrosurgery over the past five years and number of patients with ieds treated with electrosurgery. 0-500 501-1000 1001-5000 >5,000 estimated number of patients treated with electrosurgery within the past 5 years: 12 7 50 47 estimated number of patients with ieds (pacemaker, cardioverter-defibrillator, cochlear implant, deep brain/spinal/nerve stimulator) treated with electrosurgery in the past 5 years: 85 19 11 0 skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 330 table 4. routinely (>90%) implemented precautions by cutaneous surgeons performing electrosurgery in patients with an implantable electronic device. routinely (>90%) implemented precautions icd; % respondent s (n) pacemaker; % respondent s (n) deep brain stimulator/cochle ar implant; % respondents (n) spinal cord/nerve stimulator; % respondent s (n) utilize only short bursts of current (<5 sec) 63% (101) 70% (98) 60% (72) 62% (62) avoid use around device 63% (100) 67% (95) 56% (67) 58% (59) use of minimal power/lowest effective settings 54% (86) 67% (94) 57% (68) 54% (55) code/crash cart available 47% (75) 50% (70) 45% (54) 42% (41) have staff available trained in acls 44% (69) 42% (60) 42% (50) 36% (36) preand postoperative monitoring (bp, hr) 42% (68) 42% (59) 32% (39) 32% (33) use of bipolar forceps (coag/pinch forceps) 30% (48) 25% (36) 29% (35) 24% (24) use only true heat cautery devices 28% (46) 16% (23) 24% (29) 19% (20) placement of dispersive (grounding) plate to avoid pathway of ied 24% (38) 23% (32) 23% (28) 18% (18) identify device (location, type, manufacturer, programming parameters, date of manufacture/implantation) 17% (27) 22% (31) 19% (24) 15% (16) establish level of pacemaker dependence na 18% (26) na na neurology/neurosurgery/e nt consultation na na 10% (12) 7% (7) deactivate device 8% (12) 2% (3) 4% (5) 8% (8) cardiology consultation 5% (8) 5% (7) na na intraoperative monitoring (bp, hr) 4% (7) 6% (8) 2% (2) 1% (1) change pacemaker to fixed rate mode na 3% (4) na na preand postoperative ekg 1% (1) 1% (1) na na skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 331 historically, the presence of an implantable electronic device was considered a contraindication to the use of electrosurgery.5 ieds are at risk of sensing extrinsic electromagnetic potentials, which is referred to as electromagnetic interference (emi). a few examples of external medical sources of electromagnetic potentials include electrosurgery, magnetic resonance imaging, lithotripsy, radiation therapy, radiofrequency catheter ablation, and transcutaneous electrical nerve stimulation. numerous nonmedical potential sources of emi also exist, including cellular phones, electronic article surveillance antitheft equipment, and radiofrequency energy used for communications and radar equipment.6 potential risks of emi on cardiac ieds (pacemakers, cardioverter-defibrillators) include inhibition or triggering of the cardiac pacing system, reversion to asynchronous pacing, and faulty icd tachyarrhythmia detection.6-10 potential risks of emi on cochlear implants include device failure or permanent damage to cochlear tissues.11 nerve stimulators are at risk of damage to the device as well as changes in output and reprogramming due to electrosurgery.10 the manufacturer of deep brain stimulators warn that external electromagnetic fields may adversely affect the device and recommend against use of diathermy, therapeutic ultrasound, electrolysis, and radiation directly over the implanted site.10,12,13 recent advancements in engineering of the intrinsic design of ieds has significantly increased resistance to emi, therefore, decreasing theoretical risk of complications secondary to external electromagnetic potentials. the first dermatologic perioperative recommendations for use of electrosurgery in patients with a pacemaker were published in 1975.14 more recent guidelines were published within the dermatologic literature in 1998, however, they did not differ significantly from the original recommendations.3 the guidelines included preoperative cardiology consultation, preoperative surgical evaluation, utilizing electrocautery or bipolar forceps, deactivating icds, changing pacemakers to fixed-rate mode, use of continuous cardiac monitoring (ecg or pulse oximeter), contingency plan for arrhythmias, utilizing bursts less than 5 seconds, utilizing a minimal electrosurgical current setting, and having a cardiologist evaluation postoperatively. these recommendations were very conservative, based on complications experienced within nondermatologic electrosurgery, and did not represent consensus statements.2,3,14,15 a survey of mohs surgeons in 2001 reported a very wide variation in the precautions taken prior to electrosurgery in patients with pacemakers or implanted cardioverterdefibrillators. within this survey, 8% of mohs surgeons reported taking no unique precautions prior to electrosurgery within this population.1 similar to our survey the most commonly reported precautions were related to advanced cardiac life support (acls) training and conservative electrosurgical technique. this was also the first report of electrosurgical interference to a pacemaker or icd within a dermatologic setting.1 weaver et al. published recommendations for the use of electrosurgery in a patient with a deep brain stimulator after performing multiple electrosurgical procedures on a patient with a deep brain stimulator. the recommendations included: deactivation of the device if the tremor does not interfere with surgery; use of bipolar electrosurgical discussion skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 332 devices to reduce potential of emi; use of a dispersive plate positioned so that neither the pulse generator nor the lead wire are located between the plate and surgical site if a monopolar device must be used; use of handheld battery-operated heat cautery for hemostasis of small lesions.16 guidelines for use of electrosurgery in patients with cochlear implants were published within the dermatologic literature by behan et al. in 2017. these recommendations included: use of monoterminal and biterminal electrosurgical instruments below the clavicles with utilization of a grounding pad when possible; complete avoidance of monoterminal instruments above the clavicles; use of biterminal instrumentation with two tines above the clavicles and at least two centimeters away from the ci or any component parts.11 as demonstrated by the results of our survey and supported by el-gamal there is no clear current consensus among dermatologic surgeons regarding routine precautions in patients with an implantable electronic device. furthermore, the precautions recommended in the literature including pre-operative specialty consult, changing pacemakers to a fixed rate and intraoperative monitoring2,3,14,15 are routinely implemented less than 10%, 3%, and 6% of the time, respectively. the most commonly reported precautions in our survey were related to use of conservative electrosurgical technique with avoidance of electrosurgery in close proximity to the ied and utilization of minimal power settings and short bursts (<5 seconds). having a crash cart available and staff trained in acls were also more commonly reported. precautions that were less commonly executed included a preoperative device-specific specialty consultation (i.e., cardiology, ent, neurology, neurosurgery), deactivation of device, switching pacemaker to fixed rate mode, intraoperative monitoring of heart rate and blood pressure, and monitoring of ekg prior to and following the surgery. a total of 31 patients were estimated to have experienced emi during electrosurgery with nine reported complications. firing of a cardioverter-defibrillator was the most common complication (n=5). other reported complications included: arrhythmia/missed beats in a patient with a pacemaker (n=1), deactivation of a deep brain stimulator (n=1), and deactivation of a spinal cord stimulator or nerve stimulator (n=1). one physician reported hemi-body tetany in a patient with a deep brain stimulator after use of electrocoagulation due to failure to identify the device prior to surgery. this resulted in an urgent neurosurgery consultation. theoretical risk of emi exists for all modes of high-frequency electrosurgery. however, emi is more likely to occur when monopolar cautery is used in long (>5 seconds) or frequent bursts.6,7,17,18 bipolar electrosurgery and heat electrocautery are the preferred method of treatment in patients with an ied due to their high safety profile.1,19 as indicated in our survey, the use of true heat cautery (n=1) and bipolar (two-tip electrode) (n=1) were associated with the lowest rate of emi. electrocoagulation and electrosection are biterminal circuits which pose a greater potential risk of emi due to higher currents generated that travel throughout the patient. electrocoagulation (n=10), electrosection (n=8), and monopolar (single-tip electrode) (n=9) were more commonly reported to cause emi than any other mode of electrosurgery (rr:3.62, 95% ci:1.82-7.19). skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 333 overall, the rate of complications secondary to emi in a patient with an ied treated with electrosurgery is relatively low.1,6,15 the incidence of emi within the dermatologic literature may even be over-reported as it is thought that some reports of emi may actually be the result of interference with the electrocardiographic monitor.7,20 the rate of emi encountered in our survey 0.96 (95% ci: 0-2.15) per 1000 patients. we hypothesize that the lack of a significant association between precautions implemented and complications encountered by cutaneous surgeons performing electrosurgery in patients with an ied may be secondary to one of two theories. either the rate of complications in patients with ieds secondary to electrosurgery is so low that the precautions taken prior to the procedure are irrelevant or the precautions that are commonly implemented are effective and therefore, very few complications are encountered. limitations to this study in include recall bias, administration to acms members only resulting in small sample size, low survey response rate (10.5%), and inability to know or track the number of electrosurgery procedures performed on patients with ieds. as the population ages and technology and medicine continue to advance the use of implantable electronic devices increases. this same population with ieds is often at high risk for development of skin cancer and therefore commonly encountered by the dermatologic surgeon. adverse effects of electrosurgery in patients with an ied could pose a meaningful patient safety risk. while significant electromagnetic interference to implantable electronic devices during routine electrosurgery procedures is rare, the complications are potentially severe and costly. ideally, electrosurgery is avoided or limited in patients with an implantable electronic device. however, when necessary there is a clear lack of guidelines or current consensus among cutaneous surgeons regarding the use of electrosurgery in patients with implantable electronic devices. device-specific recommendations are necessary to ensure safety when performing electrosurgery in patients with ieds. it is imperative that dermatologic surgeons are familiar with implantable electronic devices and have a firm understanding of electrosurgery to minimize risk within this patient population. further investigation is required to formulate consensus statement recommendations for the use of electrosurgery in a patient with an implantable electronic device. this may be possible going forward with the participation in and collection of detailed data for the acms national registry of outcomes, or similar registry and outcomes work by other groups. conflict of interest disclosures: none funding: none corresponding author: eva a. hurst, md associate professor of dermatology director, dermatologic surgery 969 north mason road, suite 200 st louis, mo 63141 hurste@wustl.edu references: 1. el-gamal hm, dufresne rg, saddler k. electrosurgery, pacemakers and icds: a survey of precautions and complications experienced by cutaneous surgeons. dermatol surg. 2001;27(4):385-390. 2. sebben je. electrosurgery and cardiac pacemakers. j am acad dermatol. 1983;9(3):457-463. 3. levasseur jg, kennard cd, finley em, muse rk. dermatologic electrosurgery in patients with implantable cardioverter-defibrillators and conclusion skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 334 pacemakers. dermatol surg. 1998;24(2):233240. 4. harris pa, taylor r, thielke r, payne j, gonzalez n, conde jg. research electronic data capture (redcap)--a metadata-driven methodology and workflow process for providing translational research informatics support. j biomed inform. 2009;42(2):377-381. 5. levine pa, balady gj, lazar hl, belott ph, roberts aj. electrocautery and pacemakers: management of the paced patient subject to electrocautery. ann thorac surg. 1986;41(3):313-317. 6. howe n, cherpelis b. obtaining rapid and effective hemostasis: part ii. electrosurgery in patients with implantable cardiac devices. j am acad dermatol. 2013;69(5):677 e671-677 e679. 7. yu ss, tope wd, grekin rc. cardiac devices and electromagnetic interference revisited: new radiofrequency technologies and implications for dermatologic surgery. dermatol surg. 2005;31(8 pt 1):932-940. 8. matzke tj, christenson lj, christenson sd, atanashova n, otley cc. pacemakers and implantable cardiac defibrillators in dermatologic surgery. dermatol surg. 2006;32(9):1155-1162; discussion 1162. 9. dawes jc, mahabir rc, hillier k, cassidy m, de haas w, gillis am. electrosurgery in patients with pacemakers/implanted cardioverter defibrillators. ann plast surg. 2006;57(1):33-36. 10. tripathi s he. pacemakers, deep brain stimulators, cochlear implants, and nerve stimulators: a review of common devices in the encountered in the patient undergoing dermatologic surgery. dermatologic surgery. 2019;in press. 11. behan j, higgins s, wysong a. safety of cochlear implants in electrosurgery: a systematic review of the literature. dermatol surg. 2017;43(6):775-783. 12. martinelli pt, schulze ke, nelson br. mohs micrographic surgery in a patient with a deep brain stimulator: a review of the literature on implantable electrical devices. dermatol surg. 2004;30(7):1021-1030. 13. questions and answers about activa parkinson’s disease therapy. medtronic. http://www.medtronic.com/neuro/parkinsons/activ a_qa.html. accessed. 14. krull ea, pickard sd, hall jc. effects of electrosurgery on cardiac pacemakers. j dermatol surg. 1975;1(3):43-45. 15. riordan at, gamache c, fosko sw. electrosurgery and cardiac devices. j am acad dermatol. 1997;37(2 pt 1):250-255. 16. weaver j, kim sj, lee mh, torres a. cutaneous electrosurgery in a patient with a deep brain stimulator. dermatol surg. 1999;25(5):415-417. 17. healey js, merchant r, simpson c, et al. canadian cardiovascular society/canadian anesthesiologists' society/canadian heart rhythm society joint position statement on the perioperative management of patients with implanted pacemakers, defibrillators, and neurostimulating devices. can j cardiol. 2012;28(2):141-151. 18. pinski sl. emergencies related to implantable cardioverter-defibrillators. crit care med. 2000;28(10 suppl):n174-180. 19. boughton rs, spencer sk. electrosurgical fundamentals. j am acad dermatol. 1987;16(4):862-867. 20. fader dj, johnson tm. medical issues and emergencies in the dermatology office. j am acad dermatol. 1997;36(1):1-16; quiz 16-18. this study demonstrates daily application of this highly protective sunscreen helps minimize recurrence or development of new ak’s over 6 consecutive months. s. seite, d. moyal la roche-posay dermatological laboratories, asnières, france 1. krutmann j, berking c, berneburg m, diepgen t, dirschka t, markus s. new strategies in the prevention of actinic keratosis: a critical review. skin pharmacol physiol: 2015: 28: 281-289 2. gomes-neto a, aguilera p, prieto l, seite s, moyal d, carrera c, malvehy j, puig s. efficacy of a daily protective moisturizer with high ultraviolet b and ultraviolet a. photoprotection in decreasing ultraviolet damage: evaluation by reflectance confocal microscopy. acta dermatol venereol, 2017 introduction methods prevention of actinic keratosis by a very high uvb/uva daily photoprotectant results after 6 months, 13% of the patients developed recurrent aks, had new aks, or both. the size of the existing lesions didn’t increase. the mean number of sunscreen applications was 1.6 times per day. the sunscreen was well tolerated. actinic keratosis conclusion patients age gender phototype number of treated lesions ak lesions treatment number of remaining lesions delay of relapse (days) ak relapse status number of recurrent lesions number of new lesions 79 male ii 6 cryo 0 179 recurrence and new 2 1 68 male ii 4 pdt 1 126 new 1 65 male ii 5 cryo 18 168 new 4 74 female iv 3 cryo 11 172 new 2 62 male ii 3 cryo 3 116 new 3 71 male ii 4 cryo 0 114 new 4 53 female ii 4 cryo 2 62 recurrence and new 4 4 67 male ii 5 cryo 2 182 recurrence 1 69 male ii 3 cryo 0 50 recurrence and new 1 6 in patients with relapse (recurrence or new lesions), the total number of lesions at the inclusion (treated and remaining lesions) was significantly higher compared to the patients without relapse. in patients without relapse it was noticed that the diameter of the remaining lesions didn’t increase (1.9 mm on average). references actinic keratosis (ak) is a common pre-cancerous skin lesion caused by solar radiation exposure. regular use of sunscreen is recommended to prevent the development of ak. the goal of this study is to assess the efficacy of sunscreen with uvb and uva protection (spf100, uvapf49) in preventing ak appearance or recurrence. 70 patients between 45 and 80 years old with ak lesions were included in the study. lesions (between 2 to 6 lesions) on head, forearms or hands were treated with cryosurgery (85%) or photodynamic therapy (15%). subjects regularly applied the study sunscreen through the course of the 6 month study. treated and non-treated lesions were followed and observation of new lesions were performed over 6 months. fc17posterlarocheseitepreventionofactinickeratosis .pdf skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 345 skimages median raphe cyst: clinical and histological images susie min, ba1, sweta subhadarshani mbbs,md,mrcp(sce)2, pooja sharma md3, priyesh thakran md4 1university of cincinnati college of medicine, cincinnati, oh 2department of dermatology, university of cincinnati medical center, cincinnati, oh 3department of pathology, all india institute of medical sciences, new delhi, india 4department of dermatology and venereology, all india institute of medical sciences, new delhi, india figure 1. yellowish paramedian cystic swellings. median raphe cyst is a rare, benign cyst of congenital origin. it is usually located along the median raphe which extends from urethral meatus to the anus, with the ventral aspect of penile shaft being the most common location. a 25-year-old unmarried man presented to us with a 4-year history of swelling on his glans. this was asymptomatic and gradually progressive with no prior history of sexual contact or trauma. genital examination revealed two well defined yellowish cystic swellings of size 0.5 x 0.3 cm and 0.3 x 0.2 cm in the perifrenular area (figure 1). the cysts were excised under local anesthesia and histopathological examination revealed a cystic lesion lined partly by stratified squamous epithelium and partly by pseudostratified columnar epithelium (figure 2 a ,b). median raphe cysts develop along the median raphe of the male external genitalia with the most cases having been reported in young patients.1 they are believed to arise from trapped tissue outside of the urethral groove.2 the nomenclature for these cysts skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 346 has been varied including “mucoid cyst,” “genitoperineal cyst,” “para-meatal cyst,” “hydrocystoma,” and “apocrine figure 2. a) photomicrograph showing a cystic lesion lined partly by stratified squamous epithelium and partly by pseudostratified columnar epithelium (h&ex100), b) photomicrograph showing presence of intraepithelial goblet cells (arrow) and glandular structures. (h&ex400). cystadenoma.”3 median raphe cysts can occur at any site on the ventral side of the genital area, including the parameatus, glans penis, penile shaft, scrotum, or perineum.1 sometimes, they can present as a cordlike or canaliform induration on the median raphe.4 the differential diagnosis includes epidermal inclusion cyst, urethral diverticulum, steatocystoma, glomus tumor, dermoid cyst, and pilonidal cyst.5 histopathologically, median raphe cysts can be classified into 4 types: urethral, epidermoid, glandular, and mixed, the most common of which is the urethral type.1the present case shows the urethral type. treatment of median raphe cysts is usually local excision and aspiration for cosmetic and symptomatic purposes. potential complications include development of urethral fistulas. while most are asymptomatic, some can impact quality of life due to pain and difficulty voiding. given the rarity of the condition as well as its various presentations, median raphe cysts are often overlooked or misdiagnosed. median raphe cysts are rare non-venereal genital dermatoses. a bilateral paramedian location has not been reported in literature to the best of our knowledge. exposure to various presentations of such cysts is imperative to improve quality of life and address patients’ cosmetic concerns. conflict of interest disclosures: none funding: none corresponding author: sweta subhadarshani, mbbs,md,mrcp(sce) university of cincinnati medical center hoxworth building 3130 highland avenue ground floor, ml 0523 cincinnati, oh 45219 skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 347 email: subhadsa@mail.uc.edu references: 1. shao ih, chen td, shao ht, chen hw. male median raphe cysts: serial retrospective analysis and histopathological classification. diagn pathol. 2012;7:121. published 2012 sep 14. doi:10.1186/1746-1596-7-121 2. kurzrock ea, baskin ls, cunha gr. ontogeny of the male urethra: theory of endodermal differentiation. differentiation. 1999;64:115–122. 3. otsuka t, ueda y, terauchi m, kinoshita y. median raphe (parameatal) cysts of the penis. j urol. 1998;159:1918–1920. doi: 10.1016/s00225347(01)63196-3. 4. verma sb. canal-like median raphe cysts: an unusual presentation of an unusual condition. clin exp dermatol. 2009;34:e857–e858. 5. nagore e, sanchez-motilla jm, febrer mi, aliaga a. median raphe cysts of the penis: a report of five cases. pediatr dermatol. 1998;15:191–193. mailto:subhadsa@mail.uc.edu skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 318 brief article calcinosis cutis: case report of topical sodium thiosulfate (sts) treatment in the context of dermatomyositis rakahn haddadin bsc, omeed ahadiat, md 1 st. george’s university, school of medicine 2 university of southern california, department of dermatology calcinosis cutis (cc) results in calcium salts precipitating in the skin and subcutaneous tissue. this buildup results in a firm, white to yellow papules and plaques that can result in pain. in this case, the patient had a diagnosis of dermatomyositis which later led to the development of cc. dermatomyositis is an autoimmune process that damages the skin and leads to calcium buildup, eventually resulting in cc. dermatomyositis is an idiopathic inflammatory myopathy with characteristic cutaneous manifestations. calcinosis is an extremely painful skin condition that causes impairment in daily tasks for many patients affected. a standard treatment method is an injection of the lesions with sodium thiosulfate (sts). while this injection can often be effective in symptom relief, it tends to be extremely painful for the patient during administration. this case report discusses a patient with dermatomyositis with painful cc that was treated successfully with topical sts. the patient is a 44-year-old who had been followed in our interdisciplinary rheumatology-dermatology outpatient clinic at los angeles county +usc medical center (lac+usc) since may 2018. the patient initially presented with photodistributed poikiloderma on the lateral face, upper chest, forearms, nail fold capillary changes, violaceous papules on dorsal hands, and a poorly demarcated violaceous patch with epidermal atrophy on her left(l) breast. patient had an extensive workup, including bloodwork, ct of the chest, and two separate biopsies (two of the l breast and one of the poikiloderma plaque on her right(r) arm). blood work returned +ana 1:80, and negative for remainder of labs including dsdna, ssa, ssb, anti-jo, scl-70, anticentromere and myomarker panel. ct chest found patchy ground-glass opacities. both skin biopsies showed interface dermatitis with increased dermal mucin. l breast biopsy abstract a 44-year-old woman with dermatomyositis had multiple painful calcinosis cutis lesions that were affecting her daily living. many tests and labs were run to assess the severity and the progression of these lesions. multiple treatment options were tried and failed before, leading to an introduction of topical sodium thiosulfate. the topical formula provided a great decrease in pain and discomfort for the patient. this led to the patient never needing injectable treatment that would have caused more pain both physically and emotionally. introduction case report skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 319 also showed microcalcifications consistent with calcinosis cutis. with the constellation of cutaneous findings, interface dermatitis/increased dermal mucin on biopsies, proximal muscle weakness, and ct chest showing ground glass opacities, the patient was diagnosed with dermatomyositis with evidence of cc. throughout the patient’s treatment course, she had been tried on prednisone, mycophenolic acid, gabapentin, diltiazem, topical hydrocortisone, and topical triamcinolone. she had various responses to her treatment modalities but continued to have significant discomfort and pain in her cc on her l breast. at a later visit, she also presented with two new indurated areas on the abdomen and back, which were thought to be morphologically consistent with cc. however, the cc on the breast provided the most bothersome to the patient. she noted that her breast tenderness was an 8/10 in intensity and was limiting her sleep and her activities of daily living. the patient was offered sts injections multiple times to help treat the cc, but she was very hesitant about the idea of injecting in an area that is already causing her significant pain and discomfort. our clinical team had noted some previous studies had shown benefits to providing sts in a topical application.5,6 this idea was offered to the patient with the possibility that topical cream may not help. if topical sts failed, our next step in treatment would be administering the same medication in intralesional form. after a thorough review of prior studies, a mixture of sts with vaseline in a 1:1 ratio was created and stored in a sterile urine cup. the patient was instructed to apply the mixture to the cc lesion on the l breast once a day until her follow-up appointment. a month later, the patient reported significant improvement in pain of her l breast cc lesion on a follow-up visit. the lesion remained firm to touch on an exam, but the patient said she could sleep without pain. the patient stated that her pain, which was an 8/10, came down to 1/10 since her last visit. she reported significant improvement in her daily life activities and quality of life. she requested more topical sts solutions and never required intralesional injections of sts of her cc lesions after the two month treatment. calcinosis cutis is a severe condition that burdens the daily life of the patients affected by it. although injection of sts is a common form of treatment, it often leaves many patients uncomfortable.1 the combination of sts 25% with vaseline has been shown to improve calcinosis cutis in patients with an underlying autoimmune connective tissue disease.3 the treatment of calcinosis cutis is widely variable from case to case due to the rarity of the condition. other beneficial treatment options include warfarin, bisphosphonates, minocycline, ceftriaxone, diltiazem, and aluminum hydroxide.1 one case states that a 67 y/o woman with limited scleroderma (crest syndrome) for 20 years was diagnosed with calcinosis cutis on her fingertip.2 the patient was given topical sts 20% that was petrolatum base. in 2 months of treatment using the topical sts, the calcinosis cutis went from 3x3 to 1x1 mm.2 after 3 years, the patient's calcinosis cutis was healed and associated with a very small hyperkeratotic papule.2 in another study a 12 y/o patient with familial tumoral calcinosis syndrome presented with large subcutaneous calcification on his l elbow.3 this calcification limited the mobility of the elbow. the patient was then treated with topical sts dispersed in galen’s cerate.3 the patient applied 1.5 gm of the treatment locally for 6 months and during this time the patient noticed waning of the mass and no adverse effects were noted.3 in a retrospective study discussion skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 320 with three patients with hyperphosphatemic familial tumoral calcinosis and hyperphosphatemia hyperostosis syndrome. these three patients were each treated with topical sts after all other treatment options failed. the result of the study was a significant clinical and radiological decrease in the calcifications in each patient.4 we would like to add our case to the current literature as a successful case where symptoms of cc were alleviated with topical sts. conflict of interest disclosures: none funding: none corresponding author: rakahn haddadin, bsc email: rakahnhaddadin@gmail.com references: 1. reiter, n., el-shabrawi, l., leinweber, b., berghold, a., and aberer, e. calcinosis cutis: part ii. treatment options. (quiz 23-4)j am acad dermatol. 2011; 2. tajalli m, qureshi aa. successful treatment of calcinosis cutis of fingertip in the setting of crest syndrome with topical 20% sodium thiosulfate. jaad case rep. 2019;5(11):988– 990. published 2019 oct 28. doi:10.1016/j.jdcr.2019.08.011 3. ratsimbazafy, v., bahans, c., & guigonis, v. (2012). dramatic diminution of a large calcification treated with topical sodium thiosulfate. arthritis & rheumatism, 64(11), 3826-3826. doi:10.1002/art.34628 4. jost, j., bahans, c., courbebaisse, m., tran, t.-a., linglart, a., benistan, k., lienhardt, a., mutar, h., pfender, e., ratsimbazafy, v., & guigonis, v. (2016). topical sodium thiosulfate: a treatment for calcifications in hyperphosphatemic familial tumoral calcinosis? the journal of clinical endocrinology & metabolism, 101(7), 2810–2815. https://doi.org/10.1210/jc.2016-1087 conclusion microsoft word july 2020 bar 680 proof returned.docx skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 342 brief articles psoriasis with end stage renal disease successfully treated with ustekinumab: a case report kaylee fisher1, harry meister1, nahla shihab md1, mark lebwohl md1 1department of dermatology, icahn school of medicine at mount sinai, new york, ny psoriasis is a chronic inflammatory disease of the joints and skin, presenting as scaly erythematous dry plaques.1 the pathophysiological link between psoriasis and other chronic inflammatory conditions is thought to be driven by t cell and cytokine activation.2 ustekinumab is a human monoclonal antibody that blocks the il-12 and il-23 cytokines, which play a role in the development of psoriasis.3 for renallyeliminated compounds, acute and chronic kidney injury, can result in adverse effects and may cause drug toxicity. we report a case of a psoriasis patient who was treated with the recommended dose of ustekinumab with no observable side effects despite simultaneous kidney failure. a 34-year-old caucasian woman with a 30+ pack-year smoking history has been seen for 17 years by our department for severe plaque psoriasis primarily of the scalp, elbow, and thigh. she was initially treated topically with tacrolimus and tazarotene as well as alefacept followed by cyclosporine with minimal to moderate improvement. patient’s psoriasis ultimately cleared when initiated on etanercept and later ustekinumab when patient was concomitantly diagnosed with inflammatory bowel disease (ibd). unfortunately, several years later patient developed an unrelated post-streptococcal iga nephropathy that ultimate progressed to end-stage renal disease (esrd) requiring hemodialysis (hd). during the continual decline of her renal function and even when eventually needing hd, we continued therapy with the same dose of ustekinumab that successfully kept both her psoriasis and ibd under introduction many biologic agents are available to treat psoriasis, however only a few reports investigate the efficacy and safety of these agents in patients with psoriasis complicated by kidney failure. in this report we detail a case of severe plaque psoriasis complicated with end-stage renal disease (esrd), successfully treated with ustekinumab without need for dose adjustment. abstract case presentation skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 343 control. she eventually received a kidney transplant in 2019. chronic plaque psoriasis is an inflammatory disorder that commonly requires long-term treatment, including the use of biologic agents. as an il-17 and il-23 inhibitor, ustekinumab is an immunosuppressant that precisely blocks specific molecules from causing inflammation in the skin and joints, thereby calming inflammatory diseases such as psoriasis and ibd. in the limited number of cases of individuals with both psoriasis and renal dysfunction, no cases observed that psoriasis or the biologic agents affected the progression of kidney injury or failure.4 the patient’s kidney failure seems to have been caused by factors unrelated to her psoriasis and biologic treatment. the patient’s igan was most likely a sequalae of a streptococcal infection. extensive research has shown that the iga-binding peptides triggered by a streptococcal infection can deposit in the mesangial matrix and glomerular basement membrane, leading to kidney failure.5-6 furthermore, the patient was a significant chronic smoker, a habit that may independently lead to various medical maladies, one being glomerular injury.7 taken together, despite the many possible contributing factors to her kidney failure, the patient was treated with none-dose adjusted ustekinumab. despite patient’s renal dysfunction, she tolerated ustekinumab without adverse effects, renal or otherwise. this suggests that ustekinumab may be a safe therapeutic choice for severe plaque psoriasis in individuals with renal dysfunction.8 the use of ustekinumab to treat psoriasis may be a therapeutic option for patients who have renal dysfunction and may not require renal dose-adjustments. conflict of interest disclosures: none funding: none corresponding author: nahla shihab, md icahn school of medicine at mount sinai department of dermatology 5 e 98th street new york, ny, 10029 phone: 212-241-9728 fax: 212-987-1197 email: nahla.shihab@gmail.com references: 1. stelara (ustekinumab) fda approval history [internet]. drugs.com. [cited 2019jul25]. available from: https://www.drugs.com/history/stelara.html 2. yacoub r, habib h, lahdo a, al ali r, varjabedian l, atalla g, et al. association between smoking and chronic kidney disease: a case control study [internet]. bmc public health. biomed central; 2010 [cited 2019 jul23]. available from: https://www.ncbi.nlm.nih.gov/pmc/articles/pmc30 04836/ 3. ma c, panaccione r, khanna r, feagan bg, jairath v. il12/23 or selective il23 inhibition for the management of moderate-to-severe crohn's disease? best pract res clin gastroenterol. 2019 feb apr;38-39:101604. doi: 10.1016/j.bpg.2019.02.006. epub 2019 feb 19. review. pubmed pmid: 31327402. 4. nimmannitya k, tateishi c, mizukami y, hamamoto k, yamada s, goto h, okada s, tsuruta d. successful treatment with ustekinumab of psoriasis vulgaris in a patient undergoing hemodialysis. j dermatol. 2016 jan;43(1):92-4. doi: 10.1111/1346-8138.12989. epub 2015 jun 24. pubmed pmid: 26103788 5. schmitt r, carlsson f, mörgelin m, tati r, lindahl g, karpman d. tissue deposits of igadiscussion conclusion skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 344 binding streptococcal m proteins in iga nephropathy and henoch-schonlein purpura [internet]. the american journal of pathology. american society for investigative pathology; 2010 [cited 2019jul23]. available from: https://www.ncbi.nlm.nih.gov/pmc/articles/pmc28 08069/ 6. cha yj, lim bj, kim bs, kim y, yoo th, han sh, et al. smoking-related renal histologic injury in iga nephropathy patients [internet]. yonsei medical journal. yonsei university college of medicine; 2016 [cited 2019jul23]. available from: https://www.ncbi.nlm.nih.gov/pmc/articles/pmc46 96955/ 7. yacoub r, habib h, lahdo a, al ali r, varjabedian l, atalla g, et al. association between smoking and chronic kidney disease: a case control study [internet]. bmc public health. biomed central; 2010 [cited 2019jul29]. available from: https://www.ncbi.nlm.nih.gov/pmc/articles/pmc30 04836/ 8. yamamoto r, nagasawa y, shoji t, iwatani h, hamano t, kawada n, inoue k, uehata t, kaneko t, okada n, moriyama t, horio m, yamauchi a, tsubakihara y, imaie, rakugi h, isaka y. cigarette smoking and progression of iga nephropathy. am j kidney dis. 2010 aug;56(2):313-24. doi: 10.1053/j.ajkd.2010.02.351. epub 2010 may 14. pubmed pmid: 20471735. s. seite, d. moyal la roche-posay dermatological laboratories, asnières, france introduction methods observational study on patients with acne and at risk of post-inflammatory hyperpigmented lesions acne is one of the major reasons for dermatological consultation. post-inflammatory hyperpigmentation (pih) is sometimes associated with inflammatory lesions. the aim of this observational study was to evaluate the use of a topical formula containing ingredients (niacinamide, procerad, lha, piroctone olamine, linoleic acid) to reduce acne lesions and pih, alone or in adjunctive therapy, in patients with mild to moderate acne and post-inflammatory hyperpigmented lesions. this survey included 5232 patients (68.2% female, 31.8% male; mean age 22.9 ± 7 years old) with mild (47.9%) to moderate (47.4%) acne and was conducted by private practice dermatologists. phototypes of patients were distributed as 6.7% phototype i, 47.5% phototype ii, 38.9% phototype iii, and 6.5% phototype iv. 75.8% of patients showed residual colored marks on the face. at baseline, the dermatologists completed a questionnaire concerning the patient profile, an evaluation of clinical acne severity (gea) and noted the treatment regimen prescribed. at the second visit, planned 2 months later, dermatologists re-evaluated the acne severity, overall tolerance, reduction of seborrhea and residual colored marks. the topical skin care product was applied twice a day for 53% of patients, in the morning for 31.7% and in the evening for 15.3%. some patients used the topical skin care product alone (35.6% of patients) and others used with the same product in adjunctive therapy (64.4% of patients). results conclusion this survey demonstrated that a dermocosmetic product containing lipohydroxy acid, salicylic acid, linoleic acid, niacinamide, piroctone olamine and procerad (anti-inflammatory and anti-melanin synthesis action) can provide good results in managing acne patients with risks of post-inflammatory hyperpigmented lesions,when associated with therapeutic treatments or alone for milder acne. 80.1% of patients presented an improvement of their acne showing a significant effect (p<0.0001) of the skin care product after 2 months. a significant (p< 0.0001) decrease (-47.3% on average) of seborrhea was observed after 2 months with improvement in 88.4% of patients. there was a significant decrease (p<0.0001) of the number of patients presenting marks at the end of the study. skin care product in monotherapy severity of acne (gea) seborrhea evolution 10 ▲ ▼ 9 8 7 6 5 4 3 2 1 0 initial visit final visit l ev el o f se b o rr h ea 4.9 ± 2.1 2.6 ± 1.6 -47,3% 60% 50% 40% 30% 20% 10% 0% initial visit final visit % o f su b je ct s 8,5 0 36,4 47,9 6,6 0,6 11,1 40,6 39,3 8,3 0,6 0 mild severe moderate virtually no lesions very severe no lesions type of local treatments type of systemic treatments 20% 15% 10% 5% 0% % o f su b je ct s residual colored marks on the face there was a significant decrease (p<0.0001) of the number of patients presenting marks at the end of the study. skin care product in adjunctive therapy 17,2 59.4% of the patients had a local treatment and 19.9% a systemic treatment. 83% of patients presented an improvement of their acne showing a significant effect (p<0.0001) of the treatment associated with the skin care product after 2 months. a significant (p<0.0001) decrease (-47.3% on average) of seborrhea was observed after 2 months with improvement in 91.6% of patients. ▼ 10 ▲ 9 8 7 6 5 4 3 2 1 0 initial visit final visit l ev el o f se b o rr h ea 4.7 ± 2.1 2.4 ± 1.6 -47,3% 50% 40% 30% 20% 10% 0% final visitinitial visit % o f su b je ct s 15,3 0 36,8 43,1 4,4 0,4 17,6 44,2 32 5,8 0,4 0 mild severe moderate virtually no lesions very severe no lesions po b + ad ap ale ne as so cia tio n er yth rom yci n + tre tin oin as so cia tio n an tib iot ics az ela ic a cid re tin oid s po b ot he r lo ca l tr ea tm en t 15,5 11,8 9,5 7,1 3,3 6 10% 8% 6% 4% 2% 0% % o f su b je ct s 7,8 ho rm on al co ntr ace pti oncy cli ns an ti-a nd rog en s zin c g luc on ate ot he r s yst em ic tre atm en t 4,1 1,5 4,2 severity of acne (gea) seborrhea evolution the skin care product tolerance was evaluated by the dermatologists as high to excellent for 91.2% of the patients. 91.1% of the patients were satisfied to very satisfied by the product. 4,5 100% 80% 60% 40% 20% 0% initial visit final visit % o f su b je ct s no residual colored marks on the face residual colored marks on the face 76,1 23,9 56,4 43,6 residual colored marks on the face 100% 80% 60% 40% 20% 0% initial visit final visit % o f su b je ct s no residual colored marks on the face residual colored marks on the face 83,6 16,4 66,1 33,9 fc17posterlarocheseiteacneandlesions.pdf microsoft word 16. 666 proof done.docx skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 92 brief articles spontaneous resolution of asymptomatic papules on the face of a twoyear-old taylor s. novice, bs,1 alex m. glazer, md2 1medical student, university of michigan, ann arbor, mi 2resident, college of medicine-tucson, department of dermatology, tucson, az a nine-month old male infant presented with multiple, asymptomatic lesions on his face. two months prior to presentation, his mom noticed a single yellow-to-pink spot on his forehead. over the next several weeks, multiple similar appearing lesions developed, eventually covering most the patient’s face. the patient was progressing normally and up-to-date on all developmental milestones. physical exam revealed multiple 2-5 mm reddish brown papules on the forehead, nose, cheeks, and chin (figure 1). the patient was referred to ophthalmology for eye exam, which revealed no abnormalities. complete blood count and lipid profiles were within normal limits. the differential diagnosis included benign cephalic histiocytosis, multiple juvenile xanthogranulomas, eruptive xanthomas, and urticaria pigmentosa. biopsy was performed at an outside facility, which was consistent with benign cephalic histiocytosis. the patient was followed clinically, and at age 18 months, the lesions began to spontaneously involute. at two years of age, the lesions had fully resolved without sequalae. benign cephalic histiocytosis (bch) is considered one of the rare, self-resolving non-langerhans cell histiocytoses that occurs in infants and young children. it is characterized by an abrupt onset of multiple yellow-to-brown papules, primarily occurring on the head and neck regions, sparing distal extremities, mucous membranes, and internal organs.1-4 the disease course is benign without any associated developmental abnormalities or malformations. diabetes insipidus was reported in few cases, but a clear association with bch has not been identified. all cases resolve spontaneously over months to years without residual scarring.4 report of a case a nine-month old male infant presented with multiple, asymptomatic, and yellow-to-pink lesions on his face. physical exam revealed multiple 2-5 mm reddish brown papules on the forehead, nose, cheeks, and chin laboratory findings, developmental milestones, and ophthalmology exam were within normal limits, and biopsy was consistent with benign cephalic histiocytosis. lesions spontaneously involuted at age 18 months without treatment, and by age two, the lesions had fully resolved without sequelae. abstract skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 93 typical lesions are described as small, round to oval, and pink to brownish-yellow papules. although the name bch was coined based on its classic presentation on the cephalic region, some reports describe the initial appearance of lesions on other parts of the body, including the trunk.2,4 histopathologically, there are sheets of foamy histiocytes with oval to reniform nuclei and abundant pale to slightly amphiphilic cytoplasm lacking cytoplasmic lipids. the infiltrate, which may also contain scattered lymphocytes and eosinophils, is present in the superficial to mid-reticular dermis in close apposition to a mostly effaced overlying epidermis.3 cells are characteristically positive for cd68, factor xiiia, and cd11b [okm1] on immunohistochemical staining, however, these findings are not absolutely diagnostic of bch. cells are typically negative for cd1a, s100, and cd207 and devoid of bierbeck granules.2 the differential diagnosis includes juvenile xanthogranulomas (jxg), generalized eruptive histiocytomas, and urticaria pigmentosa.3 bch is considered to belong to the spectrum of non-langerhans cell histiocytosis, which share overlapping clinical, histologic and ultrastructural characteristics.4 key words: histiocytic disorders; lumps/bumps; benign cephalic histiocytosis; benign histiocytosis; histiocytoses; spontaneous resolution; multiple papules; cephalic papules conflict of interest disclosures: none funding: none corresponding author: taylor s. novice, bs md/mba candidate 2020 university of michigan medical school 111 north ashley st, apt 408 ann arbor, mi 48014 phone: 248-660-4877 email: tnovice@med.umich.edu figure 1. nine-month old male infant with multiple, asymptomatic 2-5 mm reddish brown papules on the forehead, nose, cheeks, and chin, which eventually resolved without scarring. references: 1. gianotti f, caputo r, ermacora e, gianni e. benign cephalic histiocytosis. archives of dermatology. 1986;122(9):1038-1043. 2. jih dm, salcedo sl, jaworsky c. benign cephalic histiocytosis: a case report and review. journal of the american academy of dermatology. 2002;47(6):908-913. 3. lange m, izycka-swieszewska e, michajlowski i, baranska-rybak w. benign cephalic histiocytosis. cutis. 2015;95(6):e15-17. 4. polat ekinci a, buyukbabani n, baykal c. novel clinical observations on benign cephalic histiocytosis in a large series. pediatric dermatology. 2017;34(4):392-397. skin barrier function at baseline, day 7 and day 14 erythema and melanin index at baseline, day 7 and day 14 1department of dermatology, xijing hospital, fourth military medical university, xi’an, china, 2la roche-posay laboratroire dermatologique, shanghai, china, 3la roche-posay laboratoire dermatologique, levallois-perret, france efficacy evaluation of a dermocosmetic with skin repair properties after fractional laser surgery in acne scars introduction objectives materials & methods results qian zhang1, dong zhang1, li wang1, rongli zhang1, jingyi wei1, lin gao1, xianghua zhang2, delphine kerob3, zhongxing zhang2 acne scars are the cause for a significant morbidity among dermatology out-patients.1 insights in the potential of fractional laser treatments have established standard laser procedures to treat acne scars.2 non-ablative fractional 1565 nm laser therapy is indicated in the reduction of pore size, acne scars, wrinkles and photoageing. however, it also causes a series of changes in skin and soft tissues, such as erythema, swelling, pain, burning and other discomfort.3, 4 the recovery period and potential side effect of post fractional laser may be important, post-laser care using dermocosmetics (dc) is highly indicated to increase the outcome of laser procedures.5, 6 the post-laser application of a specifically developed dermocosmetic balm for 14 days improves skin hydration, reduces procedure-related complications, and promotes the early recovery of skin damage after fractional laser operation of acne scars. 84 adults (76 women, 8 men) who underwent acne scar fractional laser were included in this open label study. the population was equally randomized into an active group receiving the dc balm and control group receiving a routine facial care. the sebum content (sc), cuticle water content (cwc) and transepidermal water loss (tewl) were measured using instrumental means on the 1st day before the procedure (baseline), on the 7th day after the procedure (day 7) and 14th day after the procedure (day 14), respectively. the lesional erythema and melanin index was assessed using a skin image analyzer. the occurrence of post-laser complications within 14 days after the procedure was recorded. conclusion this study evaluated the clinical efficacy and safety of a dc balm in the skin repairing process after fractional laser therapy in acne scars. references 1. tan j, beissert s, cook-bolden f, chavda r, harper j, hebert a, et al. impact of facial atrophic acne scars on quality of life: a multi-country population-based survey. am j clin dermatol. 2022;23(1):115-23. 2. sadick ns, cardona a. laser treatment for facial acne scars: a review. j cos7met laser ther. 2018;20(7-8):424-35. 3. alexis af, coley mk, nijhawan ri, luke jd, shah sk, argobi ya, et al. nonablative fractional laser resurfacing for acne scarring in patients with fitzpatrick skin phototypes iv-vi. dermatol surg. 2016;42(3):392-402. 4. degitz k. [nonablative fractional lasers: acne scars and other indications]. hautarzt. 2015;66(10):753-6. 5. guerrero d. dermocosmetic management of hyperpigmentations. ann dermatol venereol. 2012;139 suppl 4:s166-9. 6. fabbrocini g, rossi ab, thouvenin md, peraud c, mengeaud v, bacquey a, et al. fragility of epidermis: acne and post-procedure lesional skin. j eur acad dermatol venereol. 2017;31 suppl 6:3-18. funding: this study was funded by la roche-posay laboratoire dermatologique, china. acknowledgments: the authors acknowledge the editing assistance of karl patrick göritz, smws france and the art work of dominique poisson, france. figure 1 figure 2 subjects were aged between 24 and 50 years with a mean age of 39.5±8.6 years. the control group (40.03±12.65 years) was somewhat older than the dc balm group (38.76±14.09 years). 14 days after the procedure, the total effective rates of the dc balm and the control group were similar (97.6% and 92.9%, respectively). 14 days after the procedure, sc and cwc levels in the dc balm group were significantly (p<0.001) higher than in the control group (sc: 87.11±4.4µg/cm² vs 80.29±3.52 μg/cm² cwc: 22.31±3.62% vs 18.95±3.15%; figure 1). conversely, the tewl in the dc balm group was significantly less important than in the control group (14.94±3.62 g•m–2•h–1 vs 23.38±4.04 g•m–2•h–1, p<0.001); a significant improvement was observed as early as after 7 days (figure 1). after 7 and 14 days of use, the erythema and melanin index were significantly (all p<0.05) lower in the dc balm than in the control (figure 2). the incidence of post-laser complications was significantly (p<0.035) higher in the control (23.8%) than in the dc balm group (7.1%). 68.3 79.7 87.1 69.2 74.3 80.3 0 20 40 60 80 100 baseline day 7 day 14 µg /cm ² 6.8 17.6 22.3 6.7 12.2 19.0 0 5 10 15 20 25 30 baseline day 7 day 14 pe rc en ta ge 28.7 14.9 12.2 30.0 23.4 17.3 0 10 20 30 40 baseline day 7 day 14 g· m –2 ·h –1 dc balm control sebum concentration cuticle water content transepidermal water loss baseline day 7 day 14 baseline day 7 day 14 dc balm control evolution of the erythema index evolution of the melanin index between baseline and day 28 312.6* 323.8* 317.5*309.0 360.0 348.8 0 100 200 300 400 500 ar bit ra ry u nit 258.3* 221.7* 218.4* 260.4 256.4 244.3 0 50 100 150 200 250 300 350 ar bit ra ry u nit the difference between the dc balm and the control regimen was statistically significant (p<0.001) for all parameters at both post-baseline visits in favour of the dc balm. the difference between the dc balm and the control regimen was statistically significant (*p<0.05 ) for erythema and the melanin index at both post-baseline visits in favour of the dc balm. mariana.carranca barrer mariana.carranca texte tapé à la machine * mariana.carranca texte tapé à la machine * mariana.carranca texte tapé à la machine * mariana.carranca texte tapé à la machine * mariana.carranca texte tapé à la machine * mariana.carranca texte tapé à la machine * mariana.carranca texte tapé à la machine * mariana.carranca texte tapé à la machine * mariana.carranca texte tapé à la machine * mariana.carranca texte tapé à la machine * mariana.carranca texte tapé à la machine * mariana.carranca texte tapé à la machine * mariana.carranca texte tapé à la machine * mariana.carranca texte tapé à la machine * mariana.carranca texte tapé à la machine * powerpoint presentation the impact of tralokinumab on quality of life and school in patients aged 12–17 with atopic dermatitis: results from the phase 3 ecztra 6 trial amy s. paller1, jonathan i. silverberg2, h. chih-ho hong3, michael cork4, luis puig5, petra arlert6, azra kurbasic6, lise soldbro6, eric l. simpson7 1departments of dermatology and pediatrics, feinberg school of medicine, northwestern university, chicago il, usa; 2department of dermatology, george washington university, washington dc, usa; 3department of dermatology and skin science, university of british columbia and probity medical research, surrey, bc, canada; 4sheffield dermatology research, department of infection, immunity, and cardiovascular disease, the university of sheffield and sheffield teaching hospitals, nihr clinical research facility, sheffield, uk; 5department of dermatology, hospital de la santa creu i sant pau-universitat autònoma de barcelona, barcelona, spain; 6leo pharma, a/s, ballerup, denmark; 7department of dermatology, oregon health & science university, portland, or, usa • tralokinumab resulted in significantly greater adjusted cdlqi mean change vs placebo, and increased proportions of patients with cdlqi ≥6 • tralokinumab improved several patient-reported outcomes that encompass psychosocial effects of ad in this vulnerable paediatric age group, as measured by the cdlqi • tralokinumab had a substantial benefit on the impact of ad on subdomains in the cdlqi related to school/holiday at week 16 • there was a trend towards treatment benefit with tralokinumab vs placebo across multiple other psychosocial domains • the largest improvements in qol were seen in the tralokinumab 300 mg group conclusions references 1. bieber t. allergy. 2020;75:54–62; 2. tsoi lc, et al. j invest dermatol. 2019;139:1480–89; 3. popovic b, et al. j mol biol. 2017;429:208–19; 4. ng m, et al. australas j dermatol. 2018;59:e114-e17; 5. ghio d, et al. br j health psychol. 2021;26:214-31; 6. manjunath j, et al. j eur acad dermatol venereol. 2022;36:e346–e48; 7. wollenberg a, et al. presented at european society for pediatric dermatology 21st annual meeting 2022; 8. paller a, et al. presented at 2021 fall clinical dermatology conference 40th annual meeting. disclosures amy s. paller has served as an investigator for abbvie, anaptysbio, incyte, janssen, krystalbio, leo pharma, regeneron, and ucb, received honorarium for consultancy from abbvie, abeona, almirall, anaptysbio, arena, azitra, biomx, boehringer ingelheim, castle biosciences, catawba, dermira, exicure, forté, kamari, leo pharma, lilly, lifemax, novartis, pfizer, regeneron, sanofi genzyme, seanergy, and ucb, and served on a data safety monitory board for abbvie, bausch, galderma, and novan. jonathan i. silverberg is an investigator for abbvie, celgene, eli lilly and company, gsk, kiniksa, leo pharma, menlo therapeutics, realm therapeutics, regeneron, roche, and sanofi; a consultant for pfizer inc., abbvie, anacor, anaptysbio, arena pharmaceuticals, asana biosciences, dermira, dermavant, eli lilly and company, galderma, gsk, glenmark, incyte, kiniksa, leo pharma, medimmune, menlo therapeutics, novartis, realm therapeutics, regeneron, and sanofi; a speaker for regeneron and sanofi; and is on advisory boards for pfizer inc., dermira, leo pharma, and menlo therapeutics. h. chih-ho hong is a researcher, consultant, and/or advisor for abbvie, amgen, arcutis, bausch health, boehringer ingelheim, celgene, dermavant, dermira, ds biopharma, galderma, glaxosmithkline, incyte, janssen, leo pharma, lilly, medimmune, novartis, pfizer, regeneron, roche, sanofi genzyme, sun pharma, and ucb. michael cork has served as a clinical trial investigator for astellas, galapagos, johnson & johnson, leo pharma, la roche-posay, msd, novartis, perrigo, regeneron, sanofi genzyme, and stiefel; has served as an advisory board member, consultant, and/or invited lecturer for pfizer inc., amgen, astellas, bayer, johnson & johnson, leo pharma, l’oréal, msd, novartis, regeneron, sanofi genzyme, stiefel, and unilever; has received honoraria from astellas, johnson & johnson, leo pharma, novartis, regeneron, sanofi genzyme, and stiefel; and has received research funding from bayer. luís puig has received consultancy/speaker’s honoraria from and/or participated in clinical trials sponsored by abbvie, almirall, amgen, baxalta, biogen, boehringer ingelheim, celgene, gebro, janssen, jsc biocad, leo-pharma, lilly, merck-serono, msd, mylan, novartis, pfizer, regeneron, roche, sandoz, samsung-bioepis, sanofi and ucb. petra arlert, azra kurbasic, and lise soldbro are employees of leo pharma a/s. eric l. simpson is a consultant and investigator for regeneron/sanofi, dermira, menlo pharmaceuticals, lilly, abbvie, genentech, medimmune, gsk, leo pharma, celgene, and pfizer. acknowledgements the ecztra 6 clinical trial was sponsored by leo pharma a/s (ballerup, denmark). this poster is an encore of a previous presentation at the 12th international symposium on atopic dermatitis, 17 – 19 october 2022. editorial support from alphabet health (new york, ny, usa) by juliel espinosa, phd and meredith whitaker, phd was funded by leo pharma (usa). affect of ad on cdlqi domains: weeks 0-16 • at week 16, ad had ‘not at all’: • affected how embarrassed or self-conscious the patient was over the past 7 days in 49.0/47.9% of tralokinumab (150/300 mg) treated patients vs 37.0% receiving placebo (figure 2a) • affected friendships over the past 7 days in 82.3/80.2% of tralokinumab (150/300 mg) treated patients vs 71.7% receiving placebo (figure 2b) • influenced clothes you wear over the past 7 days in 55.2/55.2% of tralokinumab (150/300 mg) treated patients vs 43.5% receiving placebo (figure 2c) • affected going out, play, or hobbies over the past 7 days in 54.2/59.4% of tralokinumab (150/300 mg) treated patients vs 43.5% receiving placebo (figure 2d) • at week 16, 60.4/61.5% of tralokinumab (150/300 mg) treated patients had ‘not at all’ avoided swimming or other sports due to ad over the past 7 days vs 51.1% receiving placebo (figure 2e) • at week 16, ad had ‘not at all’: • affected school/holiday over the past 7 days in 44.8/49.0% of tralokinumab (150/300 mg) treated patients vs 28.3% receiving placebo (figure 2f) • impacted trouble with other people over the past 7 days in 83.3/82.3% of tralokinumab (150/300 mg) treated patients vs 78.3% receiving placebo (figure 2g) • at week 16, problem with treatment affected patients ‘not at all’ over the past 7 days in 50.0/59.4% of tralokinumab (150/300 mg) treated patients vs 39.1% receiving placebo (figure 2h) 0 5 10 15 20 25 30 35 40 45 0 2 4 6 8 10 12 14 16 31.0 39.5 15.9tralokinumab 150 mg q2w (n=84) placebo (n=82) tralokinumab 300 mg q2w (n=81) r e sp o n d e rs ( % ) week cdlqi reduction ≥6b -8 -6 -4 -2 0 0 2 4 6 8 10 12 14 16 –6.1 –6.7 –4.1 tralokinumab 150 mg q2w (n=95) placebo (n=89) tralokinumab 300 mg q2w (n=94) a d ju st e d m e a n c h a n g e in c d l q i cdlqia8 * * * * ** * *** *** * week a b adata collected after permanent discontinuation of tralokinumab or initiation of rescue medication after week 2 were not included. repeated measurements model: change = treatment*week+baseline*week+region+baseline iga. in case of no post-baseline assessments, the week 2 change was imputed as 0. bpatients who received rescue medication after week 2 were considered non-responders, as were patients with missing data at week 16. *mantel-haenszel risk difference compared with placebo, stratified by region and baseline iga *p<0.05 vs placebo; **p<0.01 vs placebo; ***p<0.001 vs placebo. patients with at least baseline data available were included in the cdlqi adjusted mean change analysis (a), and patients with cdlqi ≥6 at baseline were included in the cdlqi reduction ≥6 analysis (b). cdlqi, children's dermatology life quality index; iga, investigator’s global assessment; q2w, every 2 weeks. figure 1. (a) adjusted mean change in cdlqi and (b) reduction of cdlqi ≥6 by week materials and methods study design • adolescents with moderate-to-severe ad (n=289) received tralokinumab 150 mg or 300 mg or placebo every 2 weeks (q2w) during the initial phase (weeks 0–16) • qol and impact on school was measured using the cdlqi, a 10-item questionnaire assessing patient/caregiver-reported ad impact • this analysis presents the results for most of the cdlqi subdomains (excluding ‘how itchy, sore, painful’ and ‘affected sleep’, which are addressed by other analyses elsewhere) • change and proportion of patients with ≥6-point reduction (minimal important difference) from baseline to week 16 in total cdlqi were evaluated using a linear mixed model for repeated measures and cochranmantel-haenszel test, respectively • individual cdlqi domains were evaluated with the pearson chi-square test • rescue medication [topical calcineurin inhibitor (tci), tcs, systemic treatment] was used if medically necessary (i.e., to control intolerable ad symptoms) objective • to examine the impact of tralokinumab on ad-related qol and school in adolescents during weeks 0–16 of the ecztra 6 trial (nct03526861) results change in cdlqi and reduction of cdlqi ≥6: weeks 0-16 • at week 16, adjusted mean change from baseline in cdlqi was significantly greater with tralokinumab 150 mg (–6.1) and 300 mg (–6.7) vs placebo (–4.1); difference* –2.0 (p=0.04) and –2.6 (p=0.007) respectively (figure 1a) • more patients had ≥6-point reduction (minimal important difference in adolescents) with tralokinumab 150 mg (31.0%) and 300 mg (39.5%) vs placebo (15.9%); difference* 14.1% (p=0.029) and 23.9% (p<0.001), respectively (figure 1b) introduction • tralokinumab is a fully human monoclonal antibody that binds with high affinity to interleukin-13, a key driver of atopic dermatitis (ad) pathogenesis1–3 • ad is a chronic inflammatory skin disease associated with poor quality of life (qol) and a substantial psychosocial impact in adolescents4,5 • ad is associated with poor school behaviours in adolescent patients, including poor task completion, poor connectedness and impulsivity6 • the phase 3 ecztra 6 trial (nct03526861) of patients aged 12–17 years with moderate-to-severe ad showed: • tralokinumab monotherapy had superior efficacy to placebo for all primary and key secondary efficacy endpoints, including change in children’s dermatology life quality index (cdlqi) from baseline to week 167 • here we present a detailed analysis of cdlqi results from ecztra 6 introduction scan to download a copy of this poster copies of this poster and its content, obtained through this qr code, are for personal use only and may not be reproduced without written permission from the authors figure 2. affect of ad on cdlqi domains (weeks 0-16) last observation carried forward (locf) was used for patients who used rescue medication or discontinued treatment (observation prior to rescue initiation/treatment discontinuation) or had missing data. sensitivity analyses used observed data, and locf was used for patients missing data. rescue medication was used by 56.4%, 33.7% and 29.9% in the placebo, tralokinumab 150 mg and 300 mg arms, respectively. across arms, >70% of patients used topical corticosteroids only. p values = pearson chi-square test vs placebo a b c d how embarrassed, self conscious affected friendships influenced clothes you wear affected going out, play, hobbies avoided swimming or other sports problems at school or holiday trouble with other people how much a problem is treatment e f g h d. moyal, s. seite la roche-posay dermatological laboratories, asnières, france introduction results how to treat dryness, hyperkeratosis and cracks of diabetic patients feet patients with diabetes frequently present skin changes on foot. the skin of the feet may become very dry with hyperkeratosis and cracks. we evaluated the use of a podologic dedicated emollient cream in the treatment of xerosis in diabetic foot. 3 2 1 0 d0 d14 d28 2,6 1,1 0,4 * * m ea n s co re evolution of dryness scoring *p≤0.0001 compared to d0 % of subjects with change of dryness score 6% 94% 2% 98% improved unchanged worsened d14 vs d0 d28 vs d0 3 2 1 0 d0 d14 d28 2,5 0,9 * * 0,4 m ea n s co re evolution of desquamation scoring *p≤0.0001 compared to d0 % of subjects with change of desquamation score 2% 98% 100% d14 vs d0 d28 vs d0 evolution of roughness scoring improved unchanged worsened 3 2 1 0 d0 d14 d28 m ea n s co re 2,4 0,9 0,2 * * *p≤0.0001 compared to d0 % of subjects with change of roughness score 2% 98% 100% improved unchanged worsened d14 vs d0 d28 vs d0 evolution of hyperkeratosis scoring 3 2 1 0 d0 d14 d28 2,7 1,9 1,2 * * m ea n s co re *p≤0.0001 compared to d0 % of subjects with change of hyperkeratosis score 16% 84% 100% improved unchanged worsened d14 vs d0 d28 vs d0 this study showed a very good tolerance of a specific podologic dermocosmetic on feet of diabetic patients including effectiveness in reducing the skin dryness, hyperkeratosis and cracks. conclusion tolerance : the product was well tolerated by all subjects after 28 days of application. subject 22 left foot subject 51 left foot d0 d28 d0 d28 methods 51 subjects (72.5% female, 27.5% male, 56 years old in average) suffering from type i (2%) or ii (98%) diabetes participated in the study. all subjects had dryness and callosity on the feet with a minimum score of 2 out of 4 for dryness, hyperkeratosis, roughness and desquamation. clinical signs were scored at t0 and after 4 weeks of application (twice a day) together with evaluation of skin tolerance and opinions of patients. fc17posterlarochemoyaldiabeticfeet.pdf d. moyal, s. seite la roche-posay dermatological laboratories, asnières, france introduction methods effect of air pollution on sebum rate and acne: how to manage acneic skin in a polluted environment pollution is a major concern in big cities. moreover, epidemiological and mechanistic studies suggest that air pollution can also have a negative impact on the integrity of the skin. indeed, it can result in aggravating skin sensitivity and reactivity. it has been determined that particulate matters can generate reactive oxygen species, leading to lipid and protein oxidation that can induce up-regulation of pro-inflammatory mediators. a harmful synergy between uv (particularly uva) radiation and pollution was also observed. the objective of this study was to evaluate first the effect of pollution on sebum rate and acne lesions and then, the efficiency of a skin care product routine to reduce the effects of pollution. in the first part of the study, 64 chinese women and men presenting acne were recruited. sebum rate and acne lesions numbers were evaluated each week during 8 weeks in a polluted environment (beijing, china). all subjects used the same mild cleanser and skin care to avoid variability due to different products usage. in the second part of the study, 43 of these subjects used 3 products (a purifying foaming gel, a skin care dedicated to acneic patients, a daily sun care with high uvb and uva protection level) during 4 weeks to assess the efficacy of this routine to reduce the sebum rate and acne severity in polluted environment. daily rate of air pollutants was collected from the official beijing air pollution website. relationship between sebum and air pollutants link between acne and pollution we demonstrated a significant relationship (variance analysis, shapiro-wilk test p<0.0001) between air pollutants, sebum rate and acne lesions. the higher the concentration of pm2.5, pm10 and no 2 was, the higher the sebum rate and the number of inflammatory and retentional lesions were. the best relationship was found between these parameters and the level of pollutants of the previous week. the skin care product routine significantly reduced the sebum rate (-20% in average), the acne severity (-28% at t4w), the number of inflammatory lesions (-34% at t4w) and the number of retentional lesions (-17% at t4w). results 64 patients were included in this study. among them we had 16% of male and 84% of female with mean age 25.9 years (from 18 to 42 years old). relationship between inflammatory lesions and air polluants *inflammatory lesions = papules and pustules relationship between retentional lesions and air pollutants effect of skin care products on acne and sebum in polluted environment pm2.5, pm10 and no 2 levels exceeded the oms guidelines (pm2.5 25µg/m3 24-hour mean, pm10 50µg/m3 24-hour mean, no 2 40µg/m3 annual mean). *retentional lesions = open and closed comedones pollution during the skin care products evaluation skincare products effect on sebum *p≤0.05 compared to t0w conclusion skincare products effect on the acne severity skincare products effect on the inflammatory lesions this study indicates that pollution may aggravate acne vulgaris and demonstrates in a polluted environment the interest of using adapted products to reduce sebum rate and acne severity. skincare products effect on the retentional lesions 70 60 50 40 30 20 10 0 t0w t1w t2w t3w t4w l ev el o f se b u m ( µ g /c m 2 ) 59,6 48,4 45,9 43,2 48,7 * * * * *p≤0.05 compared to t0w gea 1: virtually no lesion; gea 2: mild acne 3 2 1 0 t0w t1w t2w t3w t4w 2,0 1,8 1,7 1,7 1,4 * * * * * * m ea n g e a *p≤0.05 compared to t0w t4w 25 20 15 10 5 0 t0w t1w t2w t3w t4w 16,1 15,5 11,3 10,6 * * * m ea n in fl am m at o ry le si o n s co u n t 10,4 *p≤0.05 compared to t0w 25 20 15 10 5 0 t0w t1w t2w t3w t4w 17,7 16,3 13,8 * * * 13,2 14,2 ** * m ea n r et en ti o n al le si o n s co u n t reference krutmann j, moyal d, liu w, kandahari s, lee gs, nopadon n, xiang lf, seite s. pollution and acne: is there a link? cosmet invest dermatol: 2017, may 19: 10: 199-204 250 200 150 100 50 0 p o ll u ta n ts (m ea n p re vi o u s w ee k) 90 80 70 60 50 40 30 20 10 0 t0w t1w t2w t3w t4w t5w t6w t8w s eb u m (m ea n µ /c m 2 ) pm2,5 pm10 no 2 sebum 20 inflammatory lesions* p o ll u ta n ts (m ea n p re vi o u s w ee k) 250 200 150 100 50 0 t0w t1w t2w t3w t4w t5w t6w t8w 30 0 5 10 15 25 s eb u m (m ea n µ /c m 2 ) pm2,5 pm10 no 2 p o ll u ta n ts (m ea n p re vi o u s w ee k) 250 200 150 100 50 0 30 0 25 20 15 10 5 s eb u m (m ea n µ /c m 2 ) retentional lesions* pm2,5 pm10 no 2 350 300 250 200 150 100 50 pm2,5 pm10 no2 t0w t1w t2w t3w t4w 0 t0w t1w t2w t3w t4w t5w t6w t8w fc17posterlarochemoyalairpollution.pdf skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 642 skinmages focal hypertrichosis in an infant as the presenting sign of nevoid basal cell carcinoma syndrome natalie v. garcia, bs1, victoria jiminez, bs1, abigail m. smith, md1, and amy theos, md1,2 1university of alabama at birmingham heersink school of medicine, birmingham, al 2children’s of alabama, birmingham, al nevoid basal cell carcinoma syndrome (nbccs), or gorlin syndrome, is a neurocutaneous disorder caused by mutations in the ptch1 or, less commonly, sufu genes. mutations in these genes lead to malfunction of the sonic hedgehog pathway, causing unregulated cell proliferation and differentiation. the sonic hedgehog signaling pathway plays a crucial role in the development of many systems including the axial skeleton, limbs, gut endoderm, and the hair follicle. as a result of this unregulated cell proliferation, nbccs classically presents with dermatologic manifestations including basal cell carcinomas (bcc), palmar and plantar pits, and milia. other common manifestations introduction skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 643 include odontogenic jaw cysts, calcification of the falx cerebri, and skeletal abnormalities.1,2 as the sonic hedgehog pathway affects hair follicle growth and development, ptch1 mutations could lead to unregulated hair follicle proliferation. a case series by notay et al. highlights the presence of patches of hair as an early sign of nbccs.3 we present the case of a patient whose discrete tufts of hair led to the diagnosis of nbccs. a nine-month-old female presented for evaluation of multiple tufts of hair which had been present since four months of age. she had no other significant medical history and was born full-term without complications. at her initial visit she did not have macrocephaly. physical exam was notable for multiple focal patches of dark terminal hairs with normal underlying skin involving the right forearm, left wrist, lateral forehead, and left side of the mons pubis. she was diagnosed with localized hypertrichosis and no further workup was pursued. two years later, the patient presented with macrocephaly and developmental delay. dermatologic exam at this time revealed two new patches of hair growth in addition to the patches noted previously on exam. subsequent genetic testing found a heterozygous pathogenic mutation in the ptch1 gene, c.202-1 g>a, confirming the diagnosis. over the next ten years, she was followed by an outside dermatologist where she was treated for hundreds of basal cell carcinomas with multiple modalities including imiquimod cream, electrodessication and curettage, and co2 laser under general anesthesia. she returned to our clinic ten years after her initial diagnosis, and her isolated patches of hypertrichosis remained unchanged (figure 1,2). hypertrichosis can be either congenital or acquired, and within these categories you have both localized and generalized forms. localized hypertrichosis carries a small differential diagnosis such as nevoid hypertrichosis, becker’s nevi, or other localized symmetric hypertrichosis including the faun-tail deformity.5 this case demonstrates that nbccs should be considered within the differential diagnosis of localized hypertrichosis, as this patient is the sixth case to demonstrate this finding as an early sign of nbccs.3,4 further, it may be useful to include scattered hairy patches of skin as one of the cutaneous findings in nbccs along with palmar/plantar pits, basal cell carcinomas, and milia, as early intervention is crucial to preventative care including avoidance of irradiation, sun protective precautions, and for appropriate screening for other sequelae of nbccs. conflict of interest disclosures: none funding: none corresponding author: amy theos, md uab department of dermatology phone: (205) 638-4823 email: dermatology@childrensal.org references: 1. thalakoti s, geller t. basal cell nevus syndrome or gorlin syndrome. handb clin neurol. 2015;132:119-128. doi:10.1016/b978-0-44462702-5.00008-1 2. gorlin rj. nevoid basal cell carcinoma (gorlin) syndrome. genet med. 2004;6(6):530-539. doi:10.1097/01.gim.0000144188.15902.c4 3. notay m, kamangar f, awasthi s, fazel n. nevoid basal cell carcinoma syndrome and case report discussion mailto:dermatology@childrensal.org mailto:dermatology@childrensal.org skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 644 hairy skin patches. pediatr dermatol. 2017;34(2):e97-e98. doi:10.1111/pde.13067 4. wilson lc, ajayi-obe e, bernhard b, maas sm. patched mutations and hairy skin patches: a new sign in gorlin syndrome. am j med genet a. 2006 dec 1;140(23):2625-30. doi: 10.1002/ajmg.a.31374. pmid: 16906569. 5. vashi ra, mancini aj, paller as. primary generalized and localized hypertrichosis in children. arch dermatol. 2001;137(7):877-884. powerpoint presentation for patients with t1ahr-t2 cutaneous melanoma (n=582),3 we compared the i31-gep profile the mia nomogram in patients with t1a-hr – t2 melanomas. precision was evaluated using 95% cis for the mia and the i31-gep. mia 95% cis obtained directly from the online calculator. i31-gep 95% cis obtained using a lowess spline. the integrated 31-gene expression profile (i31-gep) test for cutaneous melanoma outperforms a clinicopathologic-only nomogram at identifying patients who can safely forego sentinel lymph node biopsy. background › national comprehensive cancer network (nccn) guidelines recommend forgoing sentinel lymph node biopsy (slnb) if the population-based point-estimate risk of positivity is <5% (t1a with no high-risk features), discuss and consider slnb if the risk is 5-10% (t1a with high-risk feature(s), t1b), and recommend slnb if the risk is >10% (t2-t4).1 › as it relates to guiding slnb recommendations, clinicians know that using t-stage provides a broad bin for recommendations, but the precision of these populationbased point estimates has generally not been published. › novel tools have been developed to improve slnb recommendations. most recently, the integrated 31-gene expression profile (i31-gep) which combines the 31-gep with clinical and pathological factors was developed to identify patients who can safely forego slnb and also provides risk of recurrence outcomes.3-10 separately, the melanoma institute of australia (mia) developed a nomogram using only clinical and pathological features, some of which were not included in the i31gep.11-12 most importantly, the mia model does not include genomic evaluation of the melanoma (table 1). acknowledgments & disclosures references › funding provided by castle biosciences. › aj and pp are on the speaker's bureau for castle biosciences. cb and bm are employees and stock and options holders at castle biosciences. methods presented at the 2022 fall clinical dermatology conference. abel jarell, md,1 christine bailey, mph,2 brian martin, phd,2 peter prieto, md, mph3 1northeast dermatology associates, pc, portsmouth, nh, 2castle biosciences, inc., friendswood, tx, 3university of rochester medical center, rochester, ny › actionability requires precision, defined here as confidence in a risk prediction of sln+ below the threshold (≤10%) where slnb is recommended to be ‘offered’. › all patients identified as having <5% risk by the i31-gep had upper 95% cis ≤10%; meaning none of these patients would have been ‘offered’ an slnb under current guidelines. › in contrast, using the mia nomogram, only 0.9% of the entire cohort had an sln+ risk <5% with 95% ci ≤10%, suggesting lack of confidence in the estimate of risk and, thus, in the decision to forgo the slnb. › separately, in a previously published cohort (n=433), patients that had an i31-gep predicted sln positivity risk <5% had a 5-year distant metastasis free survival rate of >98%,7 an outcome not reported by this mia nomogram. › in this multi-center cohort of 582 patients, the i31-gep was superior to mia in identifying t1ahr-t2 patients who could avoid slnb. furthermore, the i31-gep identified more patients traditionally thought to have a 5-10% risk (t1ahrt1b tumors) who had <5% risk (141 vs. 4) and could forego slnb. summary & conclusions scan or click here for more info 1. national comprehensive cancer guidelines, v2, 2022. 2. chen et al. oncotarget. 2016. 3. whitman et al. jco po 2021. 5. vetto et al. future oncology. 2019. 6. hsueh et al. jco po 2021. 7. jarell et al. jaad. 2022. 8. arnot et al. ajs. 2021. 9. dillon et al. cmro.2022. 10. ahmed et al. cancer med. 2022. 11. lo et al. jco 2020. 12. el sharouni et al. bjd. 2021. 13. vickers et al. bmj. 2016. 14. vickers et al. diagn progn res. 2019. figure 1. comparing point-estimate and 95% cis for i31gep and mia model and i31-gep (t1ahr-t2) › mia identified 20.8% (121/582) of patients as having <5% positivity risk, but just 0.9% (5/582) of patients had <5% risk with upper 95% cis ≤10%, casting doubt on the ability of the mia nomogram to provide precise, actionable, risk assessment. › the i31-gep identified 28.5% (166/582) of patients as having <5% positivity risk with 100% (166/166) of the upper 95% cis being ≤10%, indicating confidence in the i31-geps ability to provide actionable risk estimates. table 1: variables included in i31-gep test or mia model potential prediction variables included in i31-gep test relative importance* included in mia model relative importance** 31-gep continuous score √ 91.3 p<.001 breslow thickness √ 53.5 p<.001 √ 1.75 (per mm) mitotic rate √ 20.7 p<.001 √ 1.89-2.47 (1-4+/mm2) ulceration √ 19.1 p<.001 √ 1.32 (presence) age √ 10.5 p=.001 √ 0.97 (per year) tils lvi √ 4.31 (presence) microsatellites sex histopathologic subtype √ 0.06– 2.15 (pure desmoplastic-acral) transected bases tumor site regression *log-likelihood value (g2); reported in whitman et al. 2021. **odds ratio; reported in lo et al. 2020 › patients are included in the <5% risk category when the upper 95% ci is also ≤10%. patients are included in the >10% risk category when the lower 95% ci is also ≥5%. table 2. reclassification of risk in patients with 5-10% risk (t1ahrt1b tumors) for whom guidance is not definitive. test nccn risk reclassified as <5% risk, % (n/n) reclassified as >10% risk, % (n/n) total reclassified, % (n/n) i31-gep 5-10% risk (t1ahr-t1b), n=284 49.6% (141/284) 10.6% (30/284) 60.2% (171/284) mia 1.4% (4/284) 12.3% (35/284) 13.7% (39/284) clinical issue and aim to make evidence-based decisions about performing slnb, clinicians should have confidence that patients predicted to have <5% risk by a model are truly low-risk based on the model's precision, measured by 95% cis that do not cross clinically relevant decision thresholds. to answer this clinical question, we evaluated the i31-gep and subsequently compared it to the melanoma institute of australia (mia) developed nomogram model. https://castlebiosciences.com/research-development/publications/ direct and indirect effects of crisaborole ointment on quality of life in patients with atopic dermatitis: a mediation analysis eric simpson,1 gil yosipovitch,2 andrew g. bushmakin,3 joseph c. cappelleri,3 thomas luger,4 sonja ständer,5 wynnis tom,6 william c. ports,3 anna m. tallman,7 huaming tan,3 robert a. gerber3 1oregon health and science university, portland, or, usa; 2university of miami, miller school of medicine, miami, fl, usa; 3pfizer inc., groton, ct, usa; 4department of dermatology, university hospital münster, münster, germany; 5center for chronic pruritus, department of dermatology, university hospital münster, münster, germany; 6rady children’s hospital-san diego, san diego, ca, usa; 7pfizer inc., new york, ny, usa background • atopic dermatitis (ad) is a chronic, inflammatory skin disease characterized by intensely pruritic eczematous lesions1,2 • itch has a significant impact on quality of life (qol) in children and adults, and it is one of the most important aspects of the disease that patients use to judge treatment response3,4 • corticosteroids and calcineurin inhibitors are recommended for topical treatment of ad5-7; however, there is a need for new, effective, nonsteroidal treatments that address inflammation and itch without the potential limitations associated with current topical agents • crisaborole ointment is a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of mild to moderate ad8 – in 2 identically designed phase 3 clinical studies (ad-301: nct02118766; ad-302: nct02118792), crisaborole ointment, 2%, significantly improved global disease severity and all measured signs and symptoms of ad, and did not result in any treatment-related serious treatment-emergent adverse events8 • the most common treatment-related adverse event was application site pain (pooled ad-301 and ad-302 population; crisaborole: 4.4%, vehicle: 1.2%) • a qualitative and psychometric analysis of the severity of pruritus scale (sps), a 4-point rating scale ranging from 0 (“no itching”) to 3 (“bothersome itching/scratching which is disturbing sleep”), used in the phase 3 studies, was recently completed, supporting the use of sps as a valid measure of pruritus in ad (see posters on display by yosipovitch g et al)9,10 • mediation modeling has been used to establish the contributions of direct and indirect effects of a treatment on an outcome11,12 objectives • through mediation modeling, determine the interrelationship among patient-reported pruritus (as measured by sps), qol (as measured by the dermatology life quality index [dlqi] or the children’s dermatology life quality index [cdlqi]), and treatment using pooled data from ad-301 and ad-302 methods study treatment • in the phase 3 studies, patients aged ≥2 years were randomly assigned in a 2:1 ratio to receive crisaborole or vehicle ointment • treatment was applied twice daily for 28 days • qol was measured using the dlqi in patients aged ≥16 years and the cdlqi in patients aged 2-15 years (table 1)13,14 table 1. qol assessment scales and subscales: cdlqi and dlqi category assessment cdlqi patients aged 2-15 years dlqi patients aged ≥16 years symptoms & feelings severity of symptoms (itch, soreness, pain, stinging) 0-3 pts 0-3 pts embarrassment or self-consciousness 0-3 pts 0-3 pts personal relationships effect on friendships and social interactions (eg, teasing, bullying avoidance) 0-6 pts na effect on friendships, relatives, and/or partner, and sex life na 0-6 pts school/work & holidays effect of skin on work/school or vacation time 0-3 pts 0-3 pts leisure effect on playing sports and leisure activities 0-6 pts 0-6 pts wearing different clothes/shoes 0-3 pts na burden of treatment treatment burden on daily life 0-3 pts 0-3 pts sleep effect of skin on sleep 0-3 pts na daily activities influence on clothes worn and daily tasks na 0-6 pts total comprehensive assessment of patient qol 0-30 pts 0-30 pts cdlqi, children’s dermatology life quality index; dlqi, dermatology life quality index; na, not applicable; pts, points; qol, quality of life. pruritus scale and mediation modeling • mediation in its simplest form is represented by a third variable (m, the mediator), so that the predictor x influences the mediator m, which, in turn, influences the outcome y (x affects m and then m affects y) (figure 1)15 figure 1. basic mediation model. mediator variable (m) direct effect a b c e2 indirect effect predictor variable (x) outcome variable (y) e1 a represents the effect of the predictor (independent) variable x on the mediator variable m; b represents the direct effect of the predictor variable x on the outcome variable y; c represents the effect of the mediator variable m on the outcome variable y; e1 and e2 are the error terms. • severity of pruritus was assessed using the sps (table 2) – sps was administered via electronic diary twice a day (morning and evening, with a recall period of 24 hours) table 2. severity of pruritus scale (sps) score grade definition 0 none no itching 1 mild occasional, slight itching/scratching 2 moderate constant or intermittent itching/scratching which is not disturbing sleep 3 severe bothersome itching/scratching which is disturbing sleep • mediation model consisted of the following variables: – independent variable—treatment (crisaborole vs vehicle) – mediator variable—sps score (averaged sps scores over week 4 [days 23-29] for every patient to be consistent with 1-week recall period of the dlqi and cdlqi) – outcome variable—dlqi or cdlqi (at day 29; 1-week recall) • all available data were used, and no imputations of missing data were performed results patients demographics and disposition • between both studies, 1016 patients were randomly assigned to receive crisaborole and 506 patients were randomly assigned to receive vehicle (intent-to-treat population) • baseline demographics and disease characteristics were balanced between the treatment arms – the mean age between both groups was approximately 12.2 years; most patients (>86%) were 2-17 years of age – approximately 55.6% were female; most (80%) were non-hispanic – between both groups, distribution by race was approximately 61% white, 28% black, 5% asian, and 6% other – baseline disease characteristics are summarized in table 3 table 3: baseline disease characteristics crisaborole n = 1016 vehicle n = 506 isga, n (%) mild – 2 moderate – 3 393 (38.7) 623 (61.3) 193 (38.1) 313 (61.9) severity of pruritus,a % none – 0 mild – 1 moderate – 2 severe – 3 35 (3.9) 229 (25.4) 331 (36.7) 308 (34.1) 19 (4.3) 119 (27.0) 167 (37.9) 136 (30.8) treatable % bsa mean (sd) range 18.3 (18.02) 5-95 18.1 (17.33) 5-90 cdlqi n mean (sd) 797 9.3 (5.99) 403 9.0 (6.02) dlqi n mean (sd) 192 9.7 (6.29) 92 9.3 (6.55) bsa, body surface area; cdlqi, children’s dermatology life quality index; dlqi, dermatology life quality index; isga, investigator’s static global assessment; sd, standard deviation; sps, severity of pruritus scale. aseverity of pruritus was patientor parent/caregiver-reported and measured using the sps. presented at the 2017 fall clinical dermatology conference; october 12-15, 2017; las vegas, nv mediation models • 226 patients were included in the dlqi analysis, and 1112 patients were included in the cdlqi analysis • the indirect effect of crisaborole on qol via pruritus constituted 51% of the overall effect of active treatment (p = 0.0272) in the dlqi-based model and 72% in the cdlqi-based model (p < 0.0001) (figures 2, 3) • this suggested that the effects of crisaborole on qol were mostly mediated by improvement in severity of pruritus – the direct effect (representing all other effects) of crisaborole on qol was less than half (49% [dlqi-based model; p = 0.0365] and 28% [cdlqi-based model; p = 0.0701]) the total, or overall, effect of the active treatment on qol (figures 2, 3) figure 2. dlqi-based mediation model. pruritus (sps) direct path: 48.6% (p < 0.05) indirect path: 51.4% (p < 0.05) treatment quality of life (dlqi) sps, severity of pruritus scale; dlqi, dermatology life quality index. figure 3. cdlqi-based mediation model. pruritus (sps) direct path: 27.6% (p > 0.05) indirect path: 72.4% (p < 0.05) treatment quality of life (cdlqi) sps, severity of pruritus scale; dlqi, dermatology life quality index. conclusions • mediation modeling can be used to help explain the effect of a treatment on an outcome • the presented mediation models indicate that crisaborole affects qol mostly indirectly through improvement in the severity of pruritus • indirect effects in the cdlqi-based model were more pronounced, possibly because of differences in item composition of the questionnaires; for example, cdlqi includes sleep, which is highly affected by pruritus references 1. hong j et al. semin cutan med surg. 2011;30(2):71-86. 2. bieber t. n engl j med. 2008;358:1483-1494. 3. drucker am et al. j invest dermatol. 2017;137(1):26-30. 4. von kobyletzki lb et al. acta derm venereol. 2017;97(1):86-90. 5. eichenfield lf et al. j am acad dermatol. 2014;71:116-132. 6. schneider l et al. j allergy clin immunol. 2013;131(2):295-299.e1-27. 7. wollenberg a et al. j eur acad dermatol venereol. 2016;30(5):729-747. 8. paller as et al. j am acad dermatol. 2016;75(3):494-503.e6. 9. yosipovitch g et al. validation of the severity of pruritus scale (sps) for the assessment of pruritus in atopic dermatitis (ad). presented at: 2017 fall clinical dermatology conference; october 12-15, 2017; las vegas, nv. 10. yosipovitch g et al. the effect of crisaborole ointment, 2%, on pruritus in patients with atopic dermatitis (ad): an extended analysis. presented at: 2017 fall clinical dermatology conference; october 12-15, 2017; las vegas, nv. 11. bushmakin ag et al. j dermatolog treat. 2015;26(1):19-22. 12. panés j et al. j crohns colitis. 2016;10(11):1310-1315. 13. lewis-jones ms, finlay ay. br j dermatol. 1995;132(6):942-949. 14. finlay ay, khan gk. clin exp dermatol. 1994;19(3):210-216. 15. cappelleri jc et al. mediation models. in: patient-reported outcomes: measurement, implementation and interpretation. boca raton, fl: chapman & hall/crc press; 2013:221-259. acknowledgments editorial/medical writing support under the guidance of the authors was provided by corey mandel, phd, and robert schoen, pharmd, at apothecom, san francisco, ca, usa, and was funded by pfizer inc., new york, ny, usa, in accordance with good publication practice (gpp3) guidelines (ann intern med. 2015;163:461-464). fc17posterpfizersimpsondirectandindirecteffectsqualityoflife.pdf powerpoint presentation presented at the fall clinical dermatology conference 2022 meeting, october 20–23, 2022, las vegas, nv, usa figure 8. reasons patient stopped seeing hcp hcp: healthcare provider; sd: seborrheic dermatitis. n=43. small sample size, results are qualitive in nature. reason patient stopped seeing hcp figure 7. hcp-reported path to sd diagnosis hcp: healthcare provider; sd: seborrheic dermatitis. 77% 23% directly to dermatology hcp referral from another hcp 50% with sd as primary complaint 27% with a different/ non-sd primary complaint 6% with sd diagnosis already 17% with a different/ non-sd diagnosis figure 3. hcpand patient-reported time from symptom onset to seeking care hcp: healthcare provider. figure 1. patient demographics and disease severity patients: n=300; hcps: n=601. hcp: healthcare provider. figure 6. non-hcps who helped patients identify sd symptoms hcp: healthcare provider; sd: seborrheic dermatitis. figure 2. hcp demographics hcps (n=601) included dermatologists and nps and pas specializing in dermatology. hcp: healthcare provider; np/pa: nurse practitioner/physician assistant; sd: seborrheic dermatitis. figure 4. patient-reported initial perceptions of sd prior to diagnosis sd: seborrheic dermatitis. disclosures rc, la, ch, ma, and mz are investigators and/or consultants for arcutis biotherapeutics, inc. and received grants/research funding and/or honoraria; dc, dh, and ms are employees of arcutis biotherapeutics, inc. additional disclosures provided on request. introduction • seborrheic dermatitis (sd) is a common chronic inflammatory skin disease with a worldwide prevalence of up to 5%1; however, little is known about patient and provider views, preferences, impressions, and path to diagnosis of sd • the authors developed an online survey, conducted by the harris poll, on burden, experiences, and preferences of patients with sd and healthcare providers (hcps) • this poster presents the results related to the path to diagnosis of sd methods • the patient survey was conducted online from december 2021 through january 2022 among us adults diagnosed with sd by an hcp (figure 1) – figures for age, sex, education, race/ethnicity, region, income, household size, and marital status were weighted where necessary to bring the data into line with actual proportions in the population – self-identified black/african american patients were adjusted to natural fall out among the qualified patients – a propensity score variable was also included to adjust for respondents’ propensity to be online • the hcp survey was conducted online from december 2021 through january 2022 by hcps specializing in dermatology (including dermatologists, nurse practitioners [nps], and physician assistants [pas]) who see ≥1 patient per week and ≥1 patient with sd per year (figure 2) – for dermatologists, figures for years in practice, gender, and region were weighted where necessary to bring the data into line with actual proportions in the population – for np/pas, raw data were not weighted and are therefore only representative of the individuals who completed the survey results • hcps underestimated the time it takes for patients experiencing sd symptoms to seek care, with hcps reporting an average of 1.6 years from symptom onset to diagnosis while patients reported an average of 3.6 years (figure 3) • a higher percentage of patients with severe disease reported visiting an hcp for their symptoms within 1 year (figure 3) • before diagnosis, 56% of patients said it was hard to find information online about sd and 71% said they had not heard of sd prior to diagnosis(figure 4) – 86% of hcps said that most patients had not heard of sd prior to their diagnosis • most (83%) patients did not realize all their symptoms were due to sd and 76% mistook their symptoms for another skin condition (figure 4) – most hcps agreed that patients did not realize all their symptoms were due to sd (96%) and thought they mistook their symptoms for another skin condition (91%) • almost all (90%) patients wished they had known that there were specific symptoms to identify sd (figure 4), with 85% of hcps agreeing that their patients feel similarly • 63% of patients thought their symptoms were not severe enough to warrant medical attention, and the majority were embarrassed to talk to family or friends (59%) and hcps (58%) about symptoms (figure 5) • 77% of hcps reported that patients come to them directly about sd, with 50% having sd as their primary complaint and 6% already having an sd diagnosis (figure 7) • most (79%) patients said they prefer a dermatology hcp for sd management conclusions • prior to diagnosis, most patients said they had not heard of sd and found it difficult to find information online • hcps underestimated the time it takes for patients experiencing sd symptoms to reach out, with a 2-year difference between what hcps thought and patients reported • these findings reveal major needs in optimization of diagnosis, management, and education for sd • future studies are needed to better characterize and address these burdens raj chovatiya,1 lakshi aldredge,2 candrice heath,3 moises acevedo,4 david chu,5 diane hanna,5 melissa seal,5 matthew zirwas6 1northwestern university, chicago, il, usa; 2veterans administration portland health care system, portland, or, usa; 3temple university, philadelphia, pa, usa; 4 park plaza dermatology, new york, ny, usa; 5arcutis biotherapeutics, westlake village, ca, usa; 6dermatologists of the central states, probity medical research, and ohio university, bexley, oh, usa patient and healthcare provider perspectives on the path to diagnosis of seborrheic dermatitis: results from a national survey of adults with seborrheic dermatitis in the united states • patients reported visiting an average of 2.3 hcps for sd treatment and 75% have seen more than one hcp • patients said they visit their primary hcp for sd management an average of 4.6 times per year, and 85% said they still actively work with their hcp for sd treatment – of the 15% of patients who have stopped visiting their hcp, the reasons were improvement in symptoms (50%), ability to manage sd without prescription treatments (24%), and difficulty navigating insurance coverage for treatments (20%) (figure 8) 90% of patients wish they had known that there are specific symptoms that can help identify sd 83% “i didn’t realize all of my symptoms (e.g., on face, body, scalp, etc.) were due to sd” agree 76% “i mistook my symptoms for a different type of skin condition” agree71% “i had not heard of sd prior to my diagnosis” agree 0 20 40 60 80 100 no one else but hcp other esthetician other with sd or similar condition nutritionist friends hairstylist/barber family member patients (%) 45% 25% 22% 19% 19% 14% 5% 24% 0 20 40 60 80 100 none of these worried about safety of treatments prescribed treatment options were too expensive lack of prescription treatment options that worked insurance coverage for treatments was too difficult to navigate ability to manage symptoms without prescription treatments improvement in symptoms patients (%) 50% 24% 20% 16% 13% 5% 13% patient is actively meeting with hcp to manage sd reference 1. dessinioti c, katsambas a. clin dermatol 2013;31:343–351. acknowledgements • this study was supported by arcutis biotherapeutics, inc. • thank you to the investigators and their staff for their participation in the trial • we are grateful to the study participants and their families for their time and commitment • writing support was provided by lauren ramsey, pharmd, alligent biopharm consulting llc, and funded by arcutis biotherapeutics, inc. sex men: 55% women: 45% mean age 40 years old white: 52% hispanic: 31% black or african american: 12% asian: 3% race and ethnicity patient-reported severity hcp-reported severity mild moderate severe 71% 16%13% 19% 40% 41% sex men: 41% women: 59% mean years of practice dermatologist: 3.3 years np/pa: 2.9 years mean number of patients seen in a typical week 157.7 patients mean number of patients with sd seen per year 323.7 patients hcps patients 0 1 2 3 4 ye ar s fr om s ym pt om o ns et t o d ia gn os is hcps patients 1.5 3.6 patient-reported severity in those who sought treatment <1 year after symptom onset mild moderate severe 0 20 40 60 80 100 pa ti en ts (% ) 31% 20% 66% 85% 15% 85% yes no • before visiting an hcp for sd symptoms, patients said family members (45%), hair stylists/barbers (25%), and friends (22%) helped them identify sd as the cause of their symptoms (figure 6) • among these patients (n=223), 48% said conversations with non-hcps made them feel better. figure 5. patientand hcp-reported initial patient perceptions of sd prior to diagnosis hcp: healthcare provider; sd: seborrheic dermatitis. “i didn’t think my symptoms were severe enough to warrant medical attention” “most did not think that sd symptoms warranted medical attention” 63% patients agree 66% hcps agree “i was embarrassed to talk to my family or friends about my symptoms” “most were embarrassed to talk to their family or friends about their symptoms” 59% patients agree 65% hcps agree “i was embarrassed to talk to my hcp about my symptoms” “most were embarrassed to talk to me about their symptoms” 58% patients agree 32% hcps agree patient and healthcare provider perspectives on the path to diagnosis of seborrheic dermatitis: results from a national survey of adults with seborrheic dermatitis in the united states << /ascii85encodepages false /allowtransparency false /autopositionepsfiles true /autorotatepages /none /binding /left /calgrayprofile (dot gain 20%) /calrgbprofile (srgb iec61966-2.1) /calcmykprofile (u.s. web coated \050swop\051 v2) /srgbprofile (srgb iec61966-2.1) /cannotembedfontpolicy /warning /compatibilitylevel 1.3 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/allowimagebreaks true /allowtablebreaks true /expandpage false /honorbaseurl true /honorrollovereffect false /ignorehtmlpagebreaks false /includeheaderfooter false /marginoffset [ 0 0 0 0 ] /metadataauthor () /metadatakeywords () /metadatasubject () /metadatatitle () /metricpagesize [ 0 0 ] /metricunit /inch /mobilecompatible 0 /namespace [ (adobe) (golive) (8.0) ] /openzoomtohtmlfontsize false /pageorientation /portrait /removebackground false /shrinkcontent true /treatcolorsas /mainmonitorcolors /useembeddedprofiles false /usehtmltitleasmetadata true >> ] >> setdistillerparams << /hwresolution [2400 2400] /pagesize [612.000 792.000] >> setpagedevice lawrence f. eichenfield, md,1,2 eric l. simpson, md, mcr,3 kim papp, md, phd,4 jacek c. szepietowski, md, phd, frcp (edin),5 leon kircik, md,6 darryl toth, md,7 seth b. forman, md,8 michael e. kuligowski, md, phd, mba,9 may e. venturanza, md,9 haobo ren, phd,9 amy s. paller, md10 introduction ● atopic dermatitis (ad) is a highly pruritic, chronic, inflammatory skin disease1 ● ad often begins in childhood and can persist into adolescence and adulthood2 ● janus kinases (jaks) act downstream of proinflammatory cytokines and itch mediators involved in the pathogenesis of ad3,4 ● ruxolitinib cream is a topical formulation of ruxolitinib, a selective inhibitor of jak1 and jak25 ● in two phase 3 randomized studies of identical design (true-ad1 [nct03745638] and true-ad2 [nct03745651]), ruxolitinib cream demonstrated anti-inflammatory activity with antipruritic action vs vehicle and was well tolerated in patients with ad5 objective ● to evaluate the long-term safety and disease control of ruxolitinib cream in adolescent patients with ad (aged 12–17 years) methods study design and patients ● eligible patients were aged ≥12 years with ad for ≥2 years and had an investigator’s global assessment (iga) score of 2 or 3 and 3%–20% affected body surface area (bsa), excluding scalp ● key exclusion criteria were unstable course of ad, other types of eczema, immunocompromised status, use of ad systemic therapies during the washout period and during the study, use of ad topical therapies (except bland emollients) during the washout period and during the study, and any serious illness or medical condition that could interfere with study conduct, interpretation of data, or patients’ well-being ● true-ad1 and true-ad2 had identical study designs (figure 1) – in both studies, patients were randomized (2:2:1) to 1 of 2 ruxolitinib cream strength regimens (0.75% twice daily [bid], 1.5% bid) or vehicle cream bid for 8 weeks of double-blind treatment (vehicle-controlled [vc] period); patients were instructed to continue treating lesions even if they improved – patients on ruxolitinib cream subsequently continued treatment for 44 weeks (long-term safety [lts] period); patients initially randomized to vehicle were rerandomized 1:1 (blinded) to either ruxolitinib cream regimen ■ during the lts period, patients were instructed to treat skin areas with active ad only and to stop treatment 3 days after clearance of lesions; patients were to restart treatment with ruxolitinib cream at the first sign of recurrence figure 1. study design • continuous treatment for 8 weeks • rescue treatment not permitted • treat as needed for 44 weeks • stop treatment 3 days after lesion clearance • rescue treatment not permitted vehicle-controlled period long-term safety period patients initially randomized to rux remain on their regimen patients on vehicle rerandomized 1:1 to 0.75% rux bid or 1.5% rux bid patients randomized 2:2:1 rux† visits every 4 weeks week 52day 1 week 8 recurrence of lesions clearance of lesions 1.5% rux bid (n=~240 in each study) 0.75% rux bid (n=~240 in each study) vehicle bid (n=~120 in each study) ad, atopic dermatitis; bid, twice daily; bsa, body surface area; rux, ruxolitinib cream. † patients self-evaluated recurrence of lesions between study visits and treated lesions with active ad (≤20% bsa). if lesions cleared between study visits, patients stopped treatment 3 days after lesion disappearance. if new lesions were extensive or appeared in new areas, patients contacted the investigator to determine if an unscheduled additional visit was needed. 1departments of dermatology and pediatrics, university of california san diego, san diego, ca, usa; 2rady children’s hospital, san diego, ca, usa; 3oregon health & science university, portland, or, usa; 4k. papp clinical research and probity medical research, waterloo, on, canada; 5department of dermatology, venereology, and allergology, wroclaw medical university, wroclaw, poland; 6icahn school of medicine at mount sinai, new york, ny, usa; 7xlr8 medical research and probity medical research, windsor, on, canada; 8forcare clinical research, tampa, fl, usa; 9incyte corporation, wilmington, de, usa; 10northwestern university feinberg school of medicine, chicago, il, usa assessments ● disease control was assessed by the proportion of patients who achieved no or minimal skin lesions (iga score of 0 or 1 [clear or almost clear skin]) and mean percentage of bsa affected by ad at each visit (every 4 weeks) during the lts period ● safety and tolerability assessments included the frequency of reported treatment-emergent adverse events (teaes), treatment-related adverse events, and teaes leading to treatment discontinuation ● patients initially randomized to 0.75% or 1.5% ruxolitinib cream who remained on ruxolitinib cream during the lts period were included in this analysis; patients initially on vehicle who received ruxolitinib cream during the lts are not included in this analysis statistical analyses ● data were analyzed by descriptive statistics ● the safety analysis was conducted using pooled data from both studies ● disease control data (iga 0/1 and bsa) are reported as observed results patients ● of the 1249 patients randomized in the vc period, 245 (19.6%) were between 12–17 years old ● distribution of baseline demographics and clinical characteristics for the pooled adolescent population was similar across treatment groups (table 1) table 1. adolescent patient demographics and baseline clinical characteristics (pooled) characteristic vehicle (n=45) 0.75% rux (n=108) 1.5% rux (n=92) total (n=245) age, median (range), y 14.0 (12–17) 15.0 (12–17) 15.0 (12–17) 15.0 (12–17) female, n (%) 23 (51.1) 60 (55.6) 59 (64.1) 142 (58.0) race, n (%) white 33 (73.3) 75 (69.4) 72 (78.3) 180 (73.5) black 11 (24.4) 27 (25.0) 13 (14.1) 51 (20.8) asian 1 (2.2) 0 3 (3.3) 4 (1.6) other 0 6 (5.6) 4 (4.3) 10 (4.1) region, n (%) north america 31 (68.9) 76 (70.4) 64 (69.6) 171 (69.8) europe 14 (31.1) 32 (29.6) 28 (30.4) 74 (30.2) bsa, mean (sd), % 10.8 (5.3) 10.8 (5.5) 10.4 (6.0) 10.6 (5.6) easi, mean (sd) 8.2 (5.0) 8.4 (4.6) 8.0 (5.2) 8.2 (4.9) ≤7, n (%) 23 (51.1) 48 (44.4) 45 (48.9) 116 (47.3) >7, n (%) 22 (48.9) 60 (55.6) 47 (51.1) 129 (52.7) iga, n (%) 2 13 (28.9) 25 (23.1) 23 (25.0) 61 (24.9) 3 32 (71.1) 83 (76.9) 69 (75.0) 184 (75.1) itch nrs score, mean (sd) 4.5 (2.4) 4.5 (2.3) 4.3 (2.4) 4.4 (2.4) ≥4, n (%) 24 (53.3) 60 (55.6) 50 (54.3) 134 (54.7) duration of disease, median (range), y 11.4 (2.9–16.9) 12.0 (0.1–18.1) 13.0 (2.4–17.9) 12.2 (0.1–18.1) facial involvement, n (%)* 19 (42.2) 45 (41.7) 41 (44.6) 105 (42.9) number of flares in last 12 mo, mean (sd)* 6.7 (6.8) 5.7 (8.1) 6.2 (6.9) 6.1 (7.4) bsa, body surface area; easi, eczema area and severity index; iga, investigator’s global assessment; nrs, numerical rating scale; rux, ruxolitinib cream. * patient reported. disease control ● the evaluable population for disease control consisted of 166 patients who remained on ruxolitinib cream from the vc period to the lts period (true-ad1: 0.75% ruxolitinib cream, n=46; 1.5% ruxolitinib cream, n=41; true-ad2: 0.75% ruxolitinib cream, n=43; 1.5% ruxolitinib cream, n=36) ● the proportion of patients with clear or almost clear skin (iga 0/1) was sustained or further increased during the lts period with as-needed use of ruxolitinib cream (figure 2) ● mean affected bsa during the lts period was low and generally below 3%, attesting to a mild/ limited extent of disease (figure 3) figure 2. proportion of patients† with clear or almost clear skin (iga 0/1) in the lts period in (a) true-ad1 and (b) true-ad2 pa tie nt s w ith c le ar or a lm os t c le ar s ki n (ig a of 0 o r 1 ), % (s e) pa tie nt s w ith c le ar or a lm os t c le ar s ki n (ig a of 0 o r 1 ), % (s e) 0 20 40 60 80 100 time, wk time, wk true-ad1 true-ad2 0 20 40 60 80 100 0.75% rux 1.5% rux 0.75% rux 1.5% rux 8 12 16 20 24 28 32 36 40 44 48 52 46n 43 42 39 33 34 32 29 29 31 33 33 41n 39 37 38 35 36 35 35 31 33 34 36 43n 42 40 39 38 39 34 34 36 37 34 35 36n 33 33 32 30 31 28 28 27 26 26 27 8 12 16 20 24 28 32 36 40 44 48 52 a) b) 75.6 71.8 78.4 73.7 74.3 75.0 77.1 57.1 71.0 75.8 70.6 77.8 67.4 65.1 71.4 59.0 69.7 61.8 71.9 72.4 72.4 77.4 78.8 69.7 61.1 66.7 57.6 62.5 53.3 54.8 64.3 60.7 70.4 50.0 61.5 74.1 51.2 57.1 65.0 64.1 60.5 64.1 55.9 73.5 66.7 67.6 58.8 68.6 iga, investigator’s global assessment; lts, long-term safety; rux, ruxolitinib cream; vc, vehicle controlled. † data are shown for patients who continued on ruxolitinib cream from the vc period to the lts period. figure 3. affected bsa in the lts period† in (a) true-ad1 and (b) true-ad2 time, wk time, wk true-ad1 true-ad2 0.75% rux 1.5% rux 0.75% rux 1.5% rux 46n 43 42 39 34 34 32 29 29 31 33 33 41n 39 37 38 35 36 35 35 31 33 34 36 43n 42 40 39 38 39 35 34 36 37 34 35 36n 33 33 32 30 31 28 28 27 26 26 27 m ea n (9 5% c i) to ta l a ffe ct ed b sa , % m ea n (9 5% c i) to ta l a ffe ct ed b sa , % a) b) 0 2 4 6 8 0 2 4 6 8 8 12 16 20 24 28 32 36 40 44 48 52 8 12 16 20 24 28 32 36 40 44 48 52 3.5 3.9 2.8 2.8 2.5 2.2 1.8 1.8 1.7 2.4 2.3 1.7 3.9 3.2 2.5 1.7 1.7 1.9 1.5 1.6 2.1 2.1 1.5 1.9 5.3 4.6 3.8 2.8 3.0 3.2 2.9 2.9 2.7 2.3 3.2 2.73.7 2.5 2.4 2.5 2.6 2.6 3.6 2.0 2.4 2.9 3.1 2.8 bsa, body surface area; lts, long-term safety; rux, ruxolitinib cream; vc, vehicle controlled. † data are shown for patients who continued on ruxolitinib cream from the vc period to the lts period. safety ● the safety profile of ruxolitinib cream in the lts period was consistent with the vc period ● ruxolitinib cream was well tolerated (table 2) ● application site reactions (ie, erythema, pain, or pruritus) were reported in 6 patients (4.6%) and 1 patient (1.1%) who applied 0.75% and 1.5% ruxolitinib cream, respectively table 2. adverse events in the full 52-week period (pooled)* n, % 0.75% rux (n=108) 1.5% rux (n=92) patients with teae 64 (59.3) 43 (46.7) most common teaes† upper respiratory tract infection 10 (9.3) 15 (16.3) nasopharyngitis 8 (7.4) 7 (7.6) influenza 4 (3.7) 5 (5.4) pharyngitis 3 (2.8) 5 (5.4) patients with treatment-related ae 7 (6.5) 3 (3.3) patients who discontinued due to a teae 3 (2.8) 0 patients with serious teae 0 0 ae, adverse event; lts, long-term safety; rux, ruxolitinib cream; teae, treatment-emergent ae; vc, vehicle controlled. * data are shown for patients who continued on ruxolitinib cream from the vc period to the lts period. † occurring in >5% of patients in either group. conclusions ● adolescent patients achieved disease control with ruxolitinib cream monotherapy use as needed during the lts period, comparable to previously reported findings in the overall patient population (adolescents and adults)6 – a high proportion of patients maintained clear or almost clear skin using ruxolitinib cream as needed – mean affected bsa was low throughout the lts period ● ruxolitinib cream was well tolerated over 52 weeks, with a consistent safety profile throughout the study period – the incidence of application site reactions was low disclosures lfe has served as an investigator, consultant, speaker, or data safety monitoring board member for abbvie, almirall, arcutis, asana, dermavant, eli lilly, forte biosciences, galderma, ichnos/glenmark, incyte corporation, janssen, leo pharma, novartis, ortho dermatologics, otsuka, pfizer, regeneron, and sanofi genzyme. els is an investigator for abbvie, eli lilly, galderma, kyowa hakko kirin, leo pharma, merck, pfizer, and regeneron and is a consultant with honorarium for abbvie, eli lilly, forte bio, galderma, incyte corporation, leo pharma, menlo therapeutics, novartis, pfizer, regeneron, sanofi genzyme, and valeant. kp has received honoraria or clinical research grants as a consultant, speaker, scientific officer, advisory board member, and/or steering committee member for abbvie, akros, amgen, anacor, arcutis, astellas, bausch health/valeant, baxalta, boehringer ingelheim, bristol myers squibb, can-fite, celgene, coherus, dermira, dow pharmaceuticals, eli lilly, galderma, gilead, glaxosmithkline, incyte corporation, inflarx, janssen, kyowa hakko kirin, leo pharma, meiji seika pharma, merck (msd), merck serono, mitsubishi pharma, moberg pharma, novartis, pfizer, prcl research, regeneron, roche, sanofi-aventis/genzyme, sun pharmaceuticals, takeda, and ucb. jcs has served as an advisor for abbvie, leo pharma, menlo therapeutics, novartis, pierre fabre, and trevi; has received speaker honoraria from abbvie, eli lilly, janssen-cilag, leo pharma, novartis, sanofi genzyme, and sun pharma; and has received clinical trial funding from abbvie, almirall, amgen, galapagos, holm, incyte corporation, inflarx, janssen-cilag, menlo therapeutics, merck, novartis, pfizer, regeneron, trevi, and ucb. lk has served as an investigator, consultant, or speaker for abbvie, amgen, anaptys, arcutis, dermavant, eli lilly, glenmark, incyte corporation, kamedis, leo pharma, l’oreal, menlo therapeutics, novartis, ortho dermatologics, pfizer, regeneron, sanofi, sun pharma, and taro. dt has served as an investigator for abbvie, amgen, arcutis, astellas, astion, avillion, boehringer ingelheim, celgene, dermira, dow pharmaceuticals, ds biopharma, eli lilly, f. hoffmann-la roche ltd, galderma, glaxosmithkline, incyte corporation, isotechnika, janssen, leo pharma, merck, novartis, pfizer, regeneron, and ucb biopharma. sbf has received honoraria, clinical research grants, or fees as a consultant, speaker, advisory board member, and/or investigator for abbvie, aclaris therapeutics, asana biosciences, astrazeneca, athenex, celgene corporation, cutanea life sciences, eli lilly, incyte corporation, innovaderm research, novartis, pfizer, promius pharma, regeneron, ucb, valeant pharmaceuticals north america, and xbiotech. mek was an employee and shareholder of incyte corporation at the time of development of the original presentation. mev and hr are employees and shareholders of incyte corporation. asp has served as an investigator, consultant, or data safety monitoring board member for abbvie, abeona, alcimed, almirall, amagma, anaptysbio, arena, azitra, bausch, biomx, boehringer ingeheim, castle biosciences, catawba, dermira, eli lilly, exicure, forte, galderma, incyte corporation, janssen, kamari, krystalbio, leo pharma, lifemax, naos, novan, novartis, pfizer, phoenix, pierre fabre, regeneron, sanofi genzyme, seanergy, trifecta, and ucb. acknowledgments the authors thank the patients, investigators, and investigational sites whose participation made the study possible. support for this study was provided by incyte corporation (wilmington, de, usa). writing assistance was provided by vicky kanta, phd, an employee of icon (north wales, pa, usa), and was funded by incyte corporation. references 1. langan sm, et al. lancet. 2020;396(10247):345-360. 2. silverberg nb, durán-mckinster c. dermatol clin. 2017;35(3):351-363. 3. bao l, et al. jakstat. 2013;2(3):e24137. 4. oetjen lk, et al. cell. 2017;171(1):217-228. 5. papp k, et al. j am acad dermatol. 2021;85(4):863-872. 6. papp k, et al. long-term safety and disease control with ruxolitinib cream in atopic dermatitis: results from two phase 3 studies. presented at: revolutionizing atopic dermatitis conference, june 13, 2021. long-term safety and disease control of ruxolitinib cream among adolescents with atopic dermatitis: results from two phase 3 studies presented at the fall clinical pa & np dermatology conference orlando, fl • november 12–14, 2021 to download a copy of this poster, scan code. exposure–response analysis demonstrates response to tapinarof is driven by local effects at sites of application james del rosso,1 scott guenthner,2 h. chih-ho hong,3 john e. jett,4 philip m. brown,4 david s. rubenstein,4 stephen c. piscitelli4 1jdr dermatology research/thomas dermatology, las vegas, nv, usa; 2the indiana clinical trials center, plainfield, in, usa; 3university of british columbia and probity medical research, surrey, bc, canada; 4dermavant sciences inc., morrisville, nc, usa introduction ■ tapinarof (vtama®; dermavant sciences, inc., usa) is a first-in-class, non-steroidal, topical, aryl hydrocarbon receptor agonist approved by the food and drug administration for the treatment of plaque psoriasis in adults, and under investigation for the treatment of plaque psoriasis in children down to 2 years of age and for atopic dermatitis (ad) in adults and children down to 2 years of age1 ■ tapinarof cream 1% once daily (qd) demonstrated significant efficacy versus vehicle and was well tolerated in adults with mild to severe plaque psoriasis in two identical, 12-week, pivotal phase 3 trials, psoaring 1 (nct03956355) and psoaring 2 (nct03983980)2 ■ in the long-term extension trial, psoaring 3 (nct04053387), tapinarof was well tolerated and demonstrated a high rate of complete disease clearance, ~4-month remittive effect off therapy, and durability on therapy for up to 52 weeks3 ■ topical agents that are locally effective with minimal systemic exposure are desirable for dermatologic conditions ■ there is a need for efficacious, non-steroidal topical therapies for patients with psoriasis, without restrictions relating to duration, extent of use, and application sites ■ in a phase 2a trial, topical application of tapinarof cream 1% qd under maximal use conditions in patients with extensive psoriasis (up to 46% body surface area [bsa] involvement) resulted in minimal systemic exposure4 objective ■ to evaluate the hypothesis that there is no relationship between tapinarof plasma exposure and either safety or efficacy methods trial design ■ analyses included data from 4 clinical trials of tapinarof in patients with ad or plaque psoriasis across a range of doses, patient populations, and bsa involvement (table 1) table 1. clinical trials included in tapinarof exposure–response analyses patients with ad patients with plaque psoriasis phase 2b dose-finding trial (n=247)5 phase 2a maximal-use trial (n=21)4 pivotal phase 3 trials2 psoaring 1 (n=510) psoaring 2 (n=515) trial design randomized, doubleblind, vehicle-controlled open-label randomized, double-blind, vehicle-controlled eligibility criteria patient population ad with iga score ≥3 plaque psoriasis with pga score ≥3 plaque psoriasis with pga score ≥2 age 12–65 years 18–75 years 18–75 years bsa involvement 5%–35% ≥20% 3%–20% trial drug tapinarof cream: 0.5% qd, 0.5% bid, 1% qd, 1% bid vehicle cream: qd or bid tapinarof cream: 1% qd tapinarof cream: 1% qd vehicle cream: qd pk sampling weeks 1, 2, 4, 8, and 12 days 1, 15, and 29 weeks 4 and 12 ad, atopic dermatitis; bid, twice daily; bsa, body surface area; iga, investigator global assessment; pga, physician global assessment; pk, pharmacokinetic; qd, once daily. pharmacokinetic sampling and exposure parameters ■ tapinarof plasma concentrations were measured using a highly sensitive assay that permitted assessment of drug levels to picogram (pg [10-12 g])/ml level – the lower limit of quantitation (lloq) was 50 pg/ml in the psoriasis trials and 40 pg/ml in the ad trial ■ because most samples were below the lloq (blq), the exposure–response analysis used imputed concentration values for blq samples that assumed an exposure level of approximately half of the lloq ■ pk parameters were the minimum and maximum plasma concentrations (c min and c max ) of tapinarof endpoints and statistical analysis ■ tapinarof plasma concentrations were evaluated for relationships with disease (ad or plaque psoriasis), tapinarof dose (0.5% or 1%), and application frequency (qd or twice daily [bid]) ■ a separate analysis of the maximal-use trial in psoriasis investigated whether tapinarof exposure correlated with percentage bsa affected at baseline ■ to investigate any relationship between tapinarof exposure and safety endpoints, tapinarof exposure (c min and c max ) was categorized as follows: – ‘0’ (patients randomized to vehicle) – ‘≤blq’ (patients with undetectable tapinarof exposure) – ‘>blq’ (patients with measurable tapinarof concentrations) – the >blq group was then grouped into tertiles of exposure ■ safety assessments included adverse events of special interest (aesis): folliculitis, contact dermatitis, and headache ■ efficacy assessments in patients with psoriasis included physician global assessment (pga) scores on day 29 and change from baseline in psoriasis area and severity index (pasi) scores on day 29 ■ the relationship between tapinarof exposure and efficacy was not assessed in patients with ad ■ demographics and pk concentrations were assessed in patients who received ≥1 dose of trial drug and had ≥1 pk sample (pk population) ■ efficacy–response analyses were assessed in all patients who received ≥1 dose of trial drug (safety population) results patient baseline characteristics ■ the majority of patients (58.9% [346/587]) had plaque psoriasis; 53.8% overall were male; and the mean age was 41.8 years (table 2) ■ overall, 67.8% (398/587) of patients received tapinarof and 32.2% (189/587) received vehicle – among patients in the tapinarof groups, most (69.8%) received tapinarof 1% qd; the remainder received tapinarof 0.5% qd (9.8%), 0.5% bid (10.3%), or 1% bid (10.1%) table 2. baseline patient demographics (pk population) patients with ad patients with plaque psoriasis overall (n=587)phase 2b trial (n=241)5 phase 2a maximal-use trial (n=21)4 pivotal phase 3 trials2 psoaring 1 (n=139) psoaring 2 (n=186) age, years, mean (sd) 29.5 (14.9) 51.8 (13.9) 47.9 (13.4) 52.1 (12.4) 41.8 (17.2) male, n (%) 122 (50.6) 13 (61.9) 70 (50.4) 111 (59.7) 316 (53.8) weight, kg, mean (sd) 76.8 (24.0) 97.5 (24.6) 94.1 (25.2) 93.0 (23.1) 86.8 (25.4) bmi, kg/m2, mean (sd) 27.5 (7.6) 33.1 (7.9) 32.2 (8.5) 31.8 (7.4) 30.1 (8.1) ad, atopic dermatitis; bmi, body mass index; pk, pharmacokinetic; sd, standard deviation. pharmacokinetics of tapinarof ■ tapinarof plasma exposure was low overall and below quantifiable limits in the majority (62.6% [1243/1985]) of samples using a highly sensitive assay ■ mean (sd) c min and c max were 27.6 (23.3) pg/ml and 340 (6270) pg/ml, respectively ■ there were no trends observed between tapinarof plasma concentrations and disease (ad or psoriasis), or the concentration of tapinarof cream (0.5%, 1%), or frequency (qd, bid) of application (figure 1) ■ in a separate, post hoc analysis of the psoriasis maximal-use trial, there was also no correlation between tapinarof plasma concentration and bsa in patients with psoriasis (ranging from 21%–46%) (figure 2) ■ in the maximal-use trial in patients with psoriasis, tapinarof plasma exposure declined over time, and was approximately 10-fold lower on day 29 than on day 14 figure 1. tapinarof plasma concentrations over time remained low in ad and psoriasis trials, regardless of dose or application frequency *horizontal lines indicate the lloq for the assays used in the psoriasis trials (50 pg/ml) and the ad trial (40 pg/ml). dashed lines indicate median trend lines. ad, atopic dermatitis; bid, twice daily; lloq, lower limit of quantitation; qd, once daily. figure 2. no correlation between tapinarof exposure (c max on days 1 and 29) and baseline %bsa affected in the psoriasis maximal-use trial bsa, body surface area; c max maximum plasma concentration. exposure–response analyses ■ in the phase 2a maximal-use trial, there was no relationship between tapinarof plasma exposure and efficacy in patients with psoriasis, including improvements in pga score and change from baseline in pasi score ■ there was no relationship between tapinarof exposure and aesis of folliculitis, contact dermatitis, or headache in patients with ad or psoriasis across all trials ■ there was no correlation between tapinarof plasma exposure and pasi response on day 29 (figure 3) figure 3. no correlation between tapinarof exposure (c max on day 29) and change in pasi score in psoriasis maximal-use trial c max maximum plasma concentration; pasi, psoriasis area and severity index. conclusions ■ tapinarof cream 1% qd is efficacious and well tolerated, including on intertriginous and sensitive skin areas, in patients with mild to severe plaque psoriasis ■ topical application of tapinarof cream 1% qd in patients with psoriasis or ad resulted in minimal systemic exposure ■ the maximal-use trial in psoriasis demonstrated that tapinarof plasma exposure declined over time ■ furthermore, tapinarof systemic exposure was also unrelated to %bsa affected for patients with psoriasis ■ this exposure–response analysis demonstrates a lack of dependence on systemic activity for the therapeutic efficacy of tapinarof cream references 1. dermavant sciences. vtama (tapinarof) cream, 1%: us prescribing information. 2022. https://www.vtama.com/docs/dmvt_vtama_pi.pdf. accessed july 2022. 2. lebwohl mg, et al. n engl j med. 2021;385:2219–2229. 3. strober b, et al. j am acad dermatol. 2022. https://doi.org/10.1016/j.jaad.2022.06.1171. 4. jett je, et al. am j clin dermatol. 2022;23(1):83–91. 5. peppers j, et al. j am acad dermatol. 2019;80(1):89–98. acknowledgments this trial was funded by dermavant sciences, inc. the authors thank the participating investigators, patients and their families, and colleagues involved in the conduct of the trial. j.d.r. serves as a consultant/advisor and clinical research investigator for dermavant sciences, inc. s.g. is a speaker for abbvie, aclaris, janssen, pfizer, and sun pharma. h.c.h. has received consultancy fees, honorarium, and speaker fees from dermavant sciences, inc. j.e.j., p.m.b., d.s.r., and s.c.p. are employees of dermavant science, inc. with stock options. editorial and medical writing support under the guidance of the authors was provided by apothecom, uk, and was funded by dermavant sciences, inc. in accordance with good publication practice (gpp3) guidelines (ann intern med. 2015;163:461–464). contact dr del rosso at jqdelrosso@yahoo.com with questions or comments. 0 5 25201510 1% qd 100 1,000 ta pi na ro f c on ce nt ra ti on (p g/ m l, lo g sc al e) time (hours) 0.5% qd lloq 1% bid 0.5% bid 1 20 25 30 35 40 45 50 10 100 10,000 1,000 t ap in ar o f p la sm a c m ax ( p g /m l) %bsa affected at baseline c max on day 1 (individual patients) c max on day 29 (individual patients) tapinarof dose and application frequency patient population and trials n –– 1% qd psoriasis phase 2a maximal-use trial psoaring 1 trial psoaring 2 trial 278 ad phase 2b trial –– 1% bid ad phase 2b trial 40 –– 0.5% qd ad phase 2b trial 39 –– 0.5% bid ad phase 2b trial 41 skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 710 brief article a missed diagnosis of alpha-gal allergy in the northern united states: a case report katie roster, ms1, hannah mulvihill, bs, nisha lakhi, md, mba1 1 new york medical college, valhalla, new york alpha-gal syndrome is a serious, potentially life-threatening “meat allergy” acquired from a tick bite, most commonly the lone star tick. the tick bite results in the transmission of an oligosaccharide known as galactose-alpha1,3-galactose, or “alpha-gal” into the person’s skin.1,2 the onset of alpha-gal is usually 4-6 weeks after the tick bite. when sensitization occurs, patients present with gastrointestinal symptoms, urticaria, and possible anaphylaxis 3-6 hours after meat ingestion due to an immune-mediated immunoglobulin e (ige) antibody reaction to alpha-gal, also found in non-primate mammals.1,2,3,8 diagnosis includes an ige antibody blood test. sensitized patients should be prescribed epinephrine autoinjectors and counseled to avoid mammalian meat such as beef, lamb, and pork, as well as some milk products. 1,3,5,8 primary care providers, dermatologists, and allergists are becoming more aware of alphagal syndrome. however, this may not be the case in the northern parts of the country, as alpha-gal was originally thought not to impact this region.4,7 numerous sources, including the most recent 2022 cdc guidelines on alpha-gal syndrome, site its distribution in the southeastern and eastern united states. 3,7 however, cases have recently been reported in minnesota. a recent retrospective study of patients in the mayo clinic health system found five cases reported in minnesota from 2008-2018.7 here, we report a case of alpha-gal syndrome in minnesota in september 2022. we review a case of a 59-year-old female who develops a severe reaction to red meat. delayed diagnosis can result in a preventable life-threatening anaphylaxis reaction. thus, medical providers should consider this important differential in an adult presenting in the summer months with an urticarial eruption. a 59-year-old caucasian woman with no prior medical history of allergy, developed a abstract alpha-gal syndrome is an acquired mammalian meat allergy transmitted via tick bite. herein, we describe a case of alpha-gal syndrome in the northern united states that goes unrecognized by multiple healthcare professionals. this case highlights the importance of keeping this diagnosis in mind when treating patients with unexplained urticaria and anaphylaxis. introduction case report skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 711 round pink scaly rash surrounding a tick bite she received in minnesota. at that time, she went to her primary care provider and was diagnosed with erythema migrans and treated with a 2-week course of doxycycline, and the rash subsequently resolved. thirty-four days later, she presented to a minnesota urgent care clinic with two days of rash. she reported that the rash began on the posterior neck the previous night and spread to her chest. at the urgent care clinic, she was prescribed oral prednisone (0.5-1 mg/kg) for three days for a presumptive diagnosis of urticaria. the following day, the patient presented to the emergency room with full body urticaria (figures 1 and 2), cough, shortness of breath, and throat constriction. she was treated with intramuscular epinephrine and intravenous fluid resuscitation. she was discharged the same day with a prescription for an epinephrine autoinjector and encouraged to schedule a follow-up visit with her primary care doctor. following the emergency room discharge, she continued to have flares of urticaria and developed a new rash on her posterior neck and chest. figure 1. an urticarial rash began on the arms 10 hours after meat ingestion. the following week, the patient was able to schedule a follow-up appointment with her primary care doctor. the physician recommended antihistamines and referred her to an allergist for further evaluation, with which she could not make an appointment for many months. the patient returned to her primary care doctor the following week and was tested for alpha-gal. four days later, test results revealed serum immunoglobulin e specific to alpha-gal (sige) ≥ 0.7 ku/l, confirming the diagnosis of alpha-gal. figure 2. an urticarial rash spread to the legs 30 hours after meat ingestion. we present a case of a patient in the northern united states who develops alphagal syndrome and highlight a “classic” case of alpha-gal syndrome. classic symptoms include gastrointestinal symptoms (nausea, diarrhea, vomiting, heartburn) as well as rash, hives, and life-threatening anaphylaxis reactions.1,3,5 these symptoms can be delayed and typically occur 2-8 hours after the ingestion of mammalian meat. immediate management consists of the administration of intramuscular epinephrine and intravenous discussion skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 712 crystalloids for circulatory support. systemic steroids may be used in the acute setting. subsequently, patients should be given epinephrine autoinjectors and told to avoid the consumption of red mammalian meat products.1,3,4,5 this case highlights the importance of taking a full history from patients presenting with new urticaria. commins 2020 recommends testing patients for alpha-gal who present with unexplained anaphylaxis or recurring urticaria following exposure to mammalian red-meat products such as beef, pork, rabbit, and lamb as well as gelatin-containing foods and dairy.3 a confirmatory diagnosis requires serum or plasma immunoglobulin e specific to alpha-gal (sige) ≥ 0.7 iu/ml.3,7 the patient was diagnosed with erythema migrans, an early cutaneous sign of lyme disease, before the development of the alpha-gal allergy. interestingly, alpha-gal is classically associated with the lone star tick species, which typically is not the vector for lyme disease. however, cases of other ticks sensitizing patients to alpha-gal have been reported, such as the deer tick and the ixodes ricinus species in europe.4,8 given that lyme disease is commonly spread via ixodes scapularis “deer tick,” and the lone star tick is rare in minnesota, it is possible that in this case, alpha-gal was spread via the ixodes scapularis tick.2,4,8 however, it is also possible that the patient was never infected with lyme disease, as cutaneous manifestations of lone star ticks bites may present similarly, if not identical to erythema migrans.9 this mimicking type of rash, known as southern tick-associated rash illness (stari), is not associated with borrelia burgdorferi infection.9 more research is needed to determine if the population of lone star tick is increasing in the northern united states, or if alpha-gal syndrome is associated with additional tick species not previously reported. given the uncertainty and dynamic character of alpha gal’s distribution, all healthcare workers should be aware of this important differential for urticarial eruptions. this becomes especially true in a severe lifethreatening syndrome such as this. this case report emphasizes the importance of educating current and future healthcare workers about this diagnosis in the northern united states. conflict of interest disclosures: none funding: none corresponding author: nisha a. lakhi md, mba senior director of clinical oncology, richmond university medical center senior director of research and medical education, richmond university medical center associate professor, new york medical college phone: (718) 818-1823 email: nlakhi@nymc.edu references: 1. commins sp, platts-mills tae. delayed anaphylaxis to red meat in patients with ige specific for galactose alpha-1,3-galactose (alpha-gal). curr allergy asthma rep. 2013;13(1):72-77. doi:10.1007/s11882-0120315-y 2. cdc. alpha-gal syndrome | cdc. centers for disease control and prevention. published march 28, 2022. accessed october 25, 2022. https://www.cdc.gov/ticks/alphagal/index.html 3. commins sp. diagnosis & management of alpha-gal syndrome:lessons from 2,500 patients. expert rev clin immunol. 2020;16(7):667-677. doi:10.1080/1744666x.2020.1782745 4. frontiers | discovery of alpha-gal-containing antigens in north american tick species believed to induce red meat allergy. conclusion skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 713 accessed october 10, 2022. https://www.frontiersin.org/articles/10.3389/fi mmu.2019.01056/full 5. wilson jm, schuyler aj, schroeder n, plattsmills tae. galactose-α-1,3-galactose: atypical food allergen or model ige hypersensitivity? curr allergy asthma rep. 2017;17(1):8. doi:10.1007/s11882-017-06727 6. houchens n, hartley s, commins sp, claar d, saint s. hunting for a diagnosis. n engl j med. 2021;384(5):462-467. doi:10.1056/nejmcps2017588 7. osorio grc, palraj r, nunen s van, white mj. newly recognized α-gal syndrome in the upper midwestern united states. mayo clin proc. 2022;97(9):1754-1755. doi:10.1016/j.mayocp.2022.07.003 8. pelz bj, bryce pj. pathophysiology of food allergy. pediatr clin north am. 2015;62(6):1363-1375. doi:10.1016/j.pcl.2015.07.004 9. blanton l, keith b, brzezinski w. southern tick-associated rash illness: erythema migrans is not always lyme disease. south med j. 2008 jul;101(7):759-60. microsoft word 19. 658 proof.docx skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 100 compelling comments wes anderson’s ‘exceedingly lovely’ face erin k. bartholomew ba,1 mackenzi r. mchugh bs,1 megan c. o’connor ba1 1eastern virginia medical school in wes anderson’s the grand budapest hotel, agatha is a baker with a defining feature of a facial birthmark. protagonist gustav describes agatha, “i must say, i find that girl utterly delightful. flat as a board, enormous birthmark the shape of mexico over half her face, …yet without question, without fail, always and invariably, she's exceedingly lovely.”1 agatha is depicted as sweet with her mexico birthmark noted as her only “flaw.” yet, agatha’s appearance is a far cry from the protagonists and love-interests in classic cinematography. heroes and heroines are portrayed with flawless skin, while villains are typically depicted with marred features.2 most often, the villains are troubled with scars and vascular deformities that become a visual representation of their heinous acts and poor self-worth. the contrast of perfect and flawed skin often underscores the dichotomy between good and evil, with concerns of developing a prejudice against skin diseases.2 while agatha’s defining facial feature is not remarked upon more frequently in the film, the striking spot of beauty is likely a port-wine stain. the capillary malformation on her right cheek following the v2 branch of the trigeminal nerve. over time, these cutaneous vascular malformations typically do not regress and instead, grow and darken into adulthood. later in the movie, agatha’s love, zero mustafa, notes that she succumbs to disease, dying in a few years. while not overtly stated, a potential cause of agatha’s death could be related to complications of her mexico birthmark, a cutaneous presentation of sturge-weber disease. this congenital vascular disease commonly includes vascular malformations in the brain and eyes; agatha may have succumbed to a seizure with poor vascular perfusion to her cerebral cortex. nevertheless, agatha charms viewers and protagonist zero with her shy kindness; her slight, albeit grandiose facial imperfection making her even more human. conflict of interest disclosures: none funding: none corresponding author: megan c. o’connor ba m.d. class of 2020 eastern virginia medical school norfolk, va 23507 tel: 651-357-0763 email: mco.oconnor@gmail.com references: 1. anderson w. the grand budapest hotel. faber & faber; 2014. 2. croley ja, reese v, wagner rf, jr. dermatologic features of classic movie villains: the face of evil. jama dermatol. 2017;153(6):559-564. acknowledgements: medical writing support was provided by prescott medical communications group (chicago, il) with financial support from ortho dermatologics; ortho dermatologics is a division of bausch health us, llc • presented at winter clinical dermatology conference 2022 • january 14-19, 2022 • kauai, hi synopsis � the pathogenesis of acne is multifactorial, involving follicular proliferation of cutibacterium acnes, increased sebum production and inflammation, and abnormal keratinization1,2 • effective treatment requires pharmacologic targeting of one or more of these pathophysiologic mechanisms2 � there are numerous prescription oral and topical treatments for acne such as benzoyl peroxide (bpo), retinoids, antibiotics, and hormonal therapies2 � combining three acne treatments (an antibiotic, antibacterial, and retinoid) in a once-daily topical polymeric dispersion formulation may provide greater efficacy and tolerability than single or dyad treatments � this is the first study of clindamycin phosphate 1.2%/ bpo 3.1%/adapalene 0.15% (idp-126) gel, which once approved will be the first triple-combination, fixed-dose topical acne treatment objective � to evaluate the efficacy, safety, and tolerability of idp-126 in participants with moderate-to-severe acne methods � in a phase 2, double-blind, multicenter 12-week study (nct03170388),3 participants aged ≥9 years with moderate-to-severe acne were randomized (1:1:1:1:1) to once-daily idp-126 gel, vehicle gel, or 1 of 3 component dyad combination gels � the evaluator’s global severity score (egss) was scored as follows: 0 (clear) = normal, clear skin/no evidence of acne; 1 (almost clear) = rare noninflammatory lesions, with rare noninflamed papules; 2 (mild) = some noninflammatory lesions, with few inflammatory lesions; 3 (moderate) = noninflammatory lesions predominate, with multiple inflammatory lesions: several/many comedones and papules/pustules, ≤1 nodulocystic lesion; 4 (severe) = inflammatory lesions more apparent, many comedones/papules/pustules, ≤2 nodulocystic lesions figure 1. treatment success a at week 12 (itt population) 0% 20% 40% 60% week 12 p e rc e n ta g e o f p a rt ic ip a n ts 80% 52.5% 30.3%30.5% idp-126 gel (n=146) clin / bpo gel (n=146) vehicle gel (n=148) 27.8% 8.1% *** *** *** *** bpo / adap gel (n=150) clin / adap gel (n=150) ***p<0.001 vs idp-126. adefined as at least a 2-grade reduction from baseline in evaluator’s global severity score and a score of 0 (clear) or 1 (almost clear). adap, adapalene 0.15%; bpo, benzoyl peroxide 3.1%; clin, clindamycin phosphate 1.2%; idp-126, clindamycin phosphate 1.2%/benzoyl peroxide 3.1%/adapalene 0.15%; itt, intent to treat. figure 2. lesion reduc tions at week 12 (itt population) a. in�ammatory lesions -100% -80% -60% -40% ls m e a n p e rc e n t c h a n g e f ro m b a se lin e 0% -76.4% -69.2% -64.0% -68.1% -50.4% ** ** ** *** -20% b. nonin�ammatory lesions -100% -80% -60% -40% ls m e a n p e rc e n t c h a n g e f ro m b a se lin e 0% -71.0% -60.7%-58.7%-61.1% -45.8% ** *** ** *** -20% idp-126 gel (n=146) clin / bpo gel (n=146) vehicle gel (n=148) bpo / adap gel (n=150) clin / adap gel (n=150) **p<0.01; ***p<0.001 vs idp-126. absolute inflammatory and noninflammatory lesion reductions were as follows: idp-126, 29.9 and 35.5, respectively; vehicle and dyads, range: 19.6–26.8 and 21.8–30.0 (p<0.05 vs idp-126, all). adap, adapalene 0.15%; bpo, benzoyl peroxide 3.1%; clin, clindamycin phosphate 1.2%; idp-126, clindamycin phosphate 1.2%/benzoyl peroxide 3.1%/adapalene 0.15%; itt, intent to treat; ls, least-squares. fixed-dose clindamycin phosphate 1.2%, benzoyl peroxide 3.1%, and adapalene 0.15% gel for moderate-to-severe acne: phase 2 study of the first triple-combination drug james q del rosso, do1-3; leon h kircik, md4-6; linda stein gold, md7; hilary baldwin, md8,9; jonathan s weiss, md10,11; david m pariser, md12,13; valerie callender, md14,15; edward lain, md, mba16; michael gold, md17; kenneth beer, md18; zoe d draelos, md19; neil sadick, md20,21; radhakrishnan pillai, phd22; varsha bhatt, phd22; emil a tanghetti, md23 1jdr dermatology research/thomas dermatology, las vegas, nv; 2advanced dermatology and cutaneous surgery, maitland, fl; 3touro university nevada, henderson, nv; 4indiana university school of medicine, indianapolis, in; 5physicians skin care, pllc, louisville, ky; 6icahn school of medicine at mount sinai, new york, ny; 7henry ford hospital, detroit, mi; 8the acne treatment and research center, brooklyn, ny; 9robert wood johnson university hospital, new brunswick, nj; 10georgia dermatology partners, snellville, ga; 11gwinnett clinical research center, inc., snellville, ga; 12eastern virginia medical school, norfolk, va; 13virginia clinical research, inc., norfolk, va; 14callender dermatology and cosmetic center, glenn dale, md; 15howard university college of medicine, washington dc; 16austin institute for clinical research, austin, tx; 17tennessee clinical research center, nashville, tn; 18university of miami miller school of medicine, miami, fl; 19dermatology consulting services, pllc, high point, nc; 20weill cornell medical college, new york, ny; 21sadick dermatology, new york, ny; 22bausch health us, llc, petaluma, ca*; 23center for dermatology and laser surgery, sacramento, ca *bausch health us, llc is an affiliate of bausch health companies inc. � cerave® hydrating cleanser and cerave® moisturizing lotion (l’oreal, ny) were provided as needed for optimal moisturization/cleaning of the skin � endpoints were treatment success at week 12 (≥2-grade reduction from baseline in egss and clear/almost clear skin) and least-squares (ls) mean changes from baseline to week 12 in inflammatory/ noninflammatory lesions � treatment-emergent adverse events (teaes) and cutaneous safety and tolerability (via 4-point scale where 0=none and 3=severe) were also assessed results participants � a total of 741 participants were enrolled (intent-totreat population: n=740; safety population: n=725) � mean age was approximately 19.5 years, most participants were female and white, and most had moderate disease (egss 3) at baseline (table 1) � treatment compliance across treatment groups was ≥93% efficacy � at week 12, over half of participants achieved treatment success with idp-126 vs ~30% or less with vehicle and dyads (p≤0.001, all; figure 1) � idp-126 also demonstrated significantly greater absolute reductions in the number of inflammatory and noninflammatory lesions vs vehicle or dyads, (p<0.05, all) corresponding to >70% reductions (figure 2) � images depicting acne improvements in idp-126treated participants are shown in figure 3 safety � teae rates were higher with idp-126 and bpo/adapalene vs clindamycin/bpo, clindamycin/adapalene, or vehicle at week 12 (table 2) � most teaes were of mild-to-moderate severity (data not shown) � with idp-126, there was no severe scaling, erythema, hypopigmentation, or itching, and <5% of participants had severe hyperpigmentation, burning, or stinging (table 3) figure 3. acne improvements with idp-126 13-year-old female black baseline: egss 3 il: 46 nil: 54 week 12: egss 1 il: 0 (100% reduction) nil: 21 (61% reduction) 14-year-old male asian baseline: egss 3 il: 35 nil: 40 week 12: egss 0 il: 0 (100% reduction) nil: 0 (100% reduction) 26-year-old female white baseline: egss 3 il: 36 nil: 41 week 12: egss 1 il: 1 (97% reduction) nil: 3 (93% reduction) 27-year-old female black/white baseline: egss 3 il: 30 nil: 42 week 12: egss 1 il: 4 (87% reduction) nil: 5 (88% reduction) individual results may vary. all participants self-reported ethnicity as non-hispanic/latino. egss, evaluator’s global severity score; idp-126, clindamycin phosphate 1.2%/benzoyl peroxide 3.1%/adapalene 0.15%; il, inflammatory lesions; nil, noninflammatory lesions. table 1. baseline demographics and characteristics (itt population) idp-126 gel (n=146) bpo / adap gel (n=150) clin / bpo gel (n=146) clin / adap gel (n=150) vehicle gel (n=148) age, mean (sd), y 19.9 (7.0) 19.2 (8.0) 19.6 (6.9) 19.4 (6.5) 19.6 (7.1) female, n (%) 94 (64.4) 86 (57.3) 91 (62.3) 93 (62.0) 89 (60.1) race,a n (%) white 98 (67.1) 109 (72.7) 101 (69.2) 109 (72.7) 95 (64.2) black 24 (16.4) 26 (17.3) 30 (20.5) 20 (13.3) 26 (17.6) asian 10 (6.8) 6 (4.0) 8 (5.5) 9 (6.0) 17 (11.5) inflammatory lesion count, mean (sd) 39.0 (11.8) 39.0 (10.2) 40.0 (12.8) 38.2 (7.9) 38.2 (9.2) noninflammatory lesion count, mean (sd) 51.8 (20.3) 48.0 (14.7) 49.2 (17.6) 51.1 (18.4) 50.7 (18.7) egss, n (%) 3 – moderate 124 (84.9) 119 (79.3) 124 (84.9) 129 (86.0) 127 (85.8) 4 – severe 22 (15.1) 31 (20.7) 22 (15.1) 21 (14.0) 21 (14.2) aadditional races not shown: american indian/alaska native, native hawaiian/other pacific islander, and other/multiple. adap, adapalene 0.15%; bpo, benzoyl peroxide 3.1%; clin, clindamycin phosphate 1.2%; egss, evaluator’s global severity score; idp-126, clindamycin phosphate 1.2%/benzoyl peroxide 3.1%/adapalene 0.15%; itt, intent to treat; sd, standard deviation. table 2. summary of adverse events (safety population) participants, n (%) idp-126 gel (n=141) bpo / adap gel (n=146) clin / bpo gel (n=144) clin / adap gel (n=148) vehicle gel (n=146) reporting any teae 51 (36.2) 52 (35.6) 26 (18.1) 40 (27.0) 22 (15.1) reporting any saea 1 (0.7) 0 0 3 (2.0) 0 discontinued due to teaeb 4 (2.8) 8 (5.5) 0 3 (2.0) 2 (1.4) related teaes 28 (19.9) 32 (21.9) 3 (2.1) 18 (12.2) 2 (1.4) related teaes (in ≥5% of participants in any treatment group) as pain 11 (7.8) 16 (11.0) 1 (0.7) 5 (3.4) 1 (0.7) as dryness 9 (6.4) 8 (5.5) 2 (1.4) 9 (6.1) 0 teaes leading to discontinuationc (in ≥2% of participants in any treatment group) as pain 2 (1.4) 5 (3.4) 0 2 (1.4) 0 anone of the saes were considered related to study drug. b1 participant in the vehicle gel group discontinued the study drug, but not the study, due to a teae. cpermanent withdrawal of study drug and/or early study discontinuation. adap, adapalene 0.15%; ae, adverse event; as, application site; bpo, benzoyl peroxide 3.1%; clin, clindamycin phosphate 1.2%; idp-126, clindamycin phosphate 1.2%/benzoyl peroxide 3.1%/adapalene 0.15%; sae, serious adverse event; teae, treatment-emergent adverse event. table 3. severe (grade 3) cutaneous safety and tolerability assessmentsa (safety population) participants, n (%) idp-126 gel (n=141) bpo / adap gel (n=146) clin / bpo gel (n=144) clin / adap gel (n=148) vehicle gel (n=146) scaling 0 2 (1.4) 0 2 (1.4) 0 erythema 0 2 (1.4) 0 3 (2.0) 0 hyperpigmentation 2 (1.4) 3 (2.1) 2 (1.4) 3 (2.0) 1 (0.7) itching 0 1 (0.7) 0 0 1 (0.7) burning 6 (4.3) 8 (5.5) 0 1 (0.7) 0 stinging 3 (2.1) 6 (4.1) 0 0 0 ainvestigator-assessed evaluations were scaling, erythema, hypopigmentation, and hyperpigmentation; participant-assessed evaluations were itching, burning, and stinging. hypopigmentation is not shown as there were no severe cases. adap, adapalene 0.15%; bpo, benzoyl peroxide 3.1%; clin, clindamycin phosphate 1.2%; idp-126, clindamycin phosphate 1.2%/benzoyl peroxide 3.1%/adapalene 0.15%. conclusions � once-daily treatment with the novel fixed-dose triple-combination clindamycin phosphate 1.2%/bpo 3.1%/adapalene 0.15% gel (idp-126) in a polymeric dispersion system showed superior efficacy to vehicle gel and three dyad component gels over 12 weeks in this phase 2 study of adult, adolescent, and pediatric participants with moderate-to-severe acne � idp-126 was also safe and well tolerated with low rates of discontinuations � overall, the efficacy and safety profiles of idp-126 demonstrate its potential as a new treatment option in the acne armamentarium references 1. del rosso jq, schmidt nf. cutis. 2010;85(1):15–24. 2. zaenglein al, et al. j am acad dermatol. 2016;74(5):945–73. 3. stein gold, l, et al. am j clin dermatol. 2021. doi: 10.1007/s40257-021-00650-3. author disclosures jqdr has served as a consultant, investigator, and/or speaker for ortho dermatologics, abbvie, amgen, arcutis, dermavant, epi heath, galderma, incyte, leo pharma, lilly, mc2 therapeutics, pfizer, sun pharma, and ucb lhk has acted as an investigator, advisor, speaker, and consultant for ortho dermatologics. lsg has served as investigator/consultant or speaker for ortho dermatologics, leo pharma, dermavant, incyte, novartis, abbvie, pfizer, sun pharma, ucb, arcutis and lilly. hb has served as advisor, investigator, and on speakers’ bureaus for almirall, cassiopea, foamix, galderma, ortho dermatologics, sol gel, and sun pharma. jsw is a consultant, speaker, advisor, and/or researcher for abbvie, ortho dermatologics, janssen biotech, dermira, almirall, brickell biotech, dermtech, scynexis. dmp has served as consultant to atacama therapeutics, bickel biotechnology, biofrontera ag, celgene, dermira, leo pharma, regeneron, sanofi, tdm surgitech, theravida, and ortho dermatologics; investigator for abbott laboratories, almirall, amgen, aobiome, asana biosciences, bickel biotechnology, celgene, dermavant, dermira, eli lilly, leo pharma, menlo therapeutics, merck & co., novartis, novo nordisk a/s, ortho dermatologics, pfizer, regeneron, and stiefel; on advisory board for pfizer; and on the data monitoring board for bms. vc has served as an investigator, consultant, or speaker for abbvie, galderma, l’oréal, ortho dermatologics, and vyne. el has nothing to disclose. mg has acted as an investigator, advisor, speaker, and consultant for ortho dermatologics. kb has received funding from allergan, galderma, evolus, and revance. zdd received research funding from ortho dermatologics. ns has served on advisory boards, as a consultant, investigator, speaker, and/or other and has received honoraria and/or grants/research funding from almirall, actavis, allergan, anacor pharmaceuticals, auxilium pharmaceuticals, bausch health, bayer, biorasi, btg, carma laboratories, cassiopea, celgene corporation, cutera, cynosure, dusa pharmaceuticals, eclipse medical, eli lilly and company, endo international, endymed medical, ferndale laboratories, galderma, gerson lehrman group, hydropeptide, merz aesthetics, neostrata, novartis, nutraceutical wellness, palomar medical technologies, prescriber’s choice, regeneron, roche laboratories, samumed, solta medical, storz medical ag, suneva medical, vanda pharmaceuticals, and venus concept. vb and rp are employees of bausch health us, llc and may hold stock and/or stock options in its parent company. eat has served as speaker for novartis, ortho dermatologics, sun pharma, lilly, galderma, abbvie, and dermira; served as a consultant/clinical studies for hologic, ortho dermatologics, and galderma; and is a stockholder for accure.. skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 441 short communication forestalling lidomageddon: local solutions to the nationwide shortage of lidocaine tanya shenoy, bs1, vinayak k. nahar, md, phd, ms2, melodie goodwin, pharmd2, stephen e. helms, md2, robert t. brodell, md2, william black, md2 1 university of mississippi school of medicine, jackson, ms 2 university of mississippi medical center, department of dermatology, jackson, ms local anesthetics ensure patient comfort during invasive skin procedures. manufacturers of lidocaine in the us (auromedics, fresenius kabi, hikma, and pfizer) have experienced supply chaininduced manufacturing delays that are predicted to last months to years. dermatologists must effectively manage their lidocaine or risk exhausting supplies. 1. take inventory accurate accounting of the current anesthetic inventory is important. aging vials of anesthetic should be utilized first to avoid the possibility of expiration. 2. dilute injectable lidocaine to preserve available supplies* dermatologists generally use 1.0-2.0% lidocaine for local anesthesia. however, 0.5% lidocaine provides pain control equivalent to 1.0% lidocaine.1 diluting higher concentrations of lidocaine solution stretches the available volume of injectable anesthetic. (see figure 1). 3. mix lidocaine without epinephrine and lidocaine with epinephrine* lidocaine with epinephrine (5 g/ml) in 1:100,000 or 1:200,000 ratios increases the duration of anesthesia and controls bleeding to maintain adequate anesthesia during dermatologic procedures.2 if an office has a good supply of lidocaine without epinephrine, it could be mixed 1:1 with a dwindling supply of lidocaine with epinephrine to double the available supply of anesthetic with epinephrine. 4. decrease waste: utilize prefilled syringes appropriately prefilling syringes with lidocaine solutions increases office efficiency. the united states pharmacopeia recommends disposing of these preparations after 24 hours at room temperature.2 however, unused prefilled lidocaine syringes exhibit antibiotic, antifungal and antimicrobial activity and maintain potency of the anesthesia for 1 introduction tips to maximize the available lidocaine supply skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 442 figure 1. recipes for stretching current supply of lidocaine. figure 2. recipe for preparing 1.0% and 0.5% diphenhydramine for use as a local anesthetic* *all drug compounding must be performed in compliance with united states food and drug administration and united states pharmacopeia. ** if 50cc vials of lidocaine are not available, carefully maintain the same ratio to dilute available lidocaine with 0.9% nacl or sodium bicarbonate skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 443 2 weeks.2 revisiting preparation and storage practices of prefilled lidocaine syringes can decrease waste. additionally, clinics often use 3 ml syringes and routinely draw up the full amount “in case” it is needed. a single punch or shave biopsy procedure requires less than this amount. drawing up 0.5 ml, 1.0 or 1.5 ml of lidocaine solutions for specific purposes is a more conscientious use of limited resources. 5. buffering lidocaine with sodium bicarbonate preserves lidocaine supplies in addition to decreasing injection pain.* lidocaine without epinephrine and lidocaine with epinephrine are acidic solutions that can cause a burning sensation when administered. lidocaine injectables are routinely buffered in a 9:1 ratio utilizing 8.4% sodium bicarbonate to decrease pain. utilizing a 3:1 or 5:1 ratio of lidocaine to sodium bicarbonate minimizes pain more effectively while providing adequate anesthesia and reducing the volume of lidocaine utilized.3 (see figure 1). 1. bupivacaine (marcaine) 0.25% is an alternative amide anesthetic which provides a prolonged duration of action. it should be used carefully due to a 4:1 risk of toxicity compared to lidocaine.4 effective ester anesthetics include procaine (novocaintm) and tetracaine (pontocainetm).3 2. antihistamines such as diphenhydramine are effective alternatives to “caine” anesthetics for simple procedures.5 (see figure 2). they have been widely used in patients with suspected “caine” allergies. if large amounts of dilute diphenhydramine (0.5-1.0%) are injected (10 cc), patients should be advised against driving for several hours after the procedure.5 3. normal saline (0.9%) can provide temporary anesthesia for simple procedures but is less effective than the options provided above.3, 5 this article offers specific, practical approaches to assist clinical dermatologists trying to maintain their surgical practices during the current lidocaine supply chain debacle. even after the crisis has ended, conscientious providers may wish to implement many of these practices which could save thousands of dollars for their practice each year. conflict of interest disclosures: robert t. brodell has participated in multi-center clinical trials with: corevitas (formerly corrona) psoriasis registry and novartis. stock ownership: veradermics, inc. he is also associate editor of the journal of the american academy of dermatology, faculty advisor for the american medical student research journal, and editor-in-chief of practice update: dermatology and serves as staff dermatologist at the gv (sonny) montgomery va hospital in jackson, ms. steve helms serves on editorial boards of cutis and jaad. vinayak k. nahar has received research funding from pfizer and health resources and services administration. he also serves on editorial boards of indian journal of paediatric dermatology, indian dermatology online journal, journal of dermatology nurses’ association, and international journal of women's dermatology. tanya shenoy, melodie goodwin, and william black have no relevant conflicts of interest. funding: none corresponding author: tanya shenoy, bs alternatives to lidocaine conclusion skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 444 2500 n state street jackson, mississippi 39216 email: tshenoy@umc.edu references: 1. morganroth pa, gelfand jm, jambusaria a, margolis dj, miller cj. a randomized, double-blind comparison of the total dose of 1.0% lidocaine with 1:100,000 epinephrine versus 0.5% lidocaine with 1:200,000 epinephrine required for effective local anesthesia during mohs micrographic surgery for skin cancers. j am acad dermatol. mar 2009;60(3):444-52. doi:10.1016/j.jaad.2008.08.001 2. bodie b, brodell rt, helms se. shortage of lidocaine with epinephrine: causes and solutions. journal of the american academy of dermatology. 2018;79(2):392-393. doi:10.1016/j.jaad.2018.02.035 3. vent a, surber c, graf johansen nt, et al. buffered lidocaine 1%/epinephrine 1:100,000 with sodium bicarbonate (sodium hydrogen carbonate) in a 3:1 ratio is less painful than a 9:1 ratio: a double-blind, randomized, placebo-controlled, crossover trial. journal of the american academy of dermatology. 2020;83(1):159-165. doi:10.1016/j.jaad.2019.09.088 4. latham jl, martin sn. infiltrative anesthesia in office practice. am fam physician. jun 15 2014;89(12):956-62. 5. grekin rc, auletta mj. local anesthesia in dermatologic surgery. journal of the american academy of dermatology. 1988/10/01/ 1988;19(4):599-614. doi:https://doi.org/10.1016/s01909622(88)70213-3 skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 553 skinmages successful treatment of cutaneous siderosis with pulsed dye laser mckenzie a. dirr, ba, bs1, alison m. bailey, md1, and richard marchell, md1 1department of dermatology, medical university of south carolina, charleston, sc a 52-year-old woman was referred to dermatology clinic for brown discoloration at the site of iv iron infusion for iron deficiency anemia 4 months prior (figure 1). two hours into infusion of 1000mg of ferric carboxymaltose, the site appeared discolored and slightly swollen. on examination, she had an approximately 9x10cm well-demarcated and homogenous light brown patch involving her right antecubital fossa. pulsed dye laser (pdl) was the only laser available in clinic for treatment. she was counseled on the risks, including dyschromia and scarring, and agreed to a trial of the treatment. initial test spots were performed with 595 nm pdl with the following settings: 7mm spot size, 7 to 10.5 j/cm2, and 0.45 milliseconds. she experienced mild blistering in the areas of higher fluence shortly after the procedure but was enthusiastic about the effect in the test spots (figure 2). the remainder of the patch was treated with a 7mm spot size, 8.5 j/cm2, and 0.45 milliseconds pulse duration in segments over multiple visits for patient comfort. skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 554 this case presents a patient who experienced extravasation of iron into dermal tissue with subsequent hyperpigmentation, termed cutaneous siderosis, which happens in 1.6-1.8% of patients treated with iv iron.1,2 laser therapy has been the preferred treatment modality for cutaneous siderosis, with recent use of quality-switched (qswitched) lasers that have shown promising outcomes.1 interestingly, we present an event of clinical resolution following treatment with pdl, traditionally indicated for erythematous and vascular disorders such as erythematotelangiectatic rosacea and capillary malformations.3 understanding the basic properties of ferric carboxymaltose, specifically its absorption band of 470-500nm, allows clinicians to identify appropriate lasers to treat the residual hyperpigmentation.1 heidemeyer et. al describes the importance of laser selection directed toward iron’s major absorption peak of 415 nm, as well as consideration for depth of penetration based on wavelength.1 lasers depend on selective photothermolysis, or using light wavelength, amount of energy, and pulse duration to destroy a specific chromophore. 3 pdl is typically used for the treatment of vascular abnormalities by targeting hemoglobin.3 we suspect the beneficial effect of pdl for cutaneous siderosis, seen in our case is due to the chromophore of iron being targeted by pdl in the visible spectrum. 3 it is important to note that scarring and hyperpigmentation, when pdl was used in patients with port wine stains, were reported in up to 4% and 27% of cases, respectively.4 these risks are more common in patients with skin of color, increased redness of the vascular lesion, and with higher laser doses.4 paradoxical darkening is a risk seen in tattoo removal using q-switched laser, described by eklund et. al.5 this is proposed to be due to laser’s reduction of chromophores, including ferric oxide found in reddish hues, to ferrous oxide. 3,5 notably, our patient did not develop these complications. a limitation of this report is the low generalizability of our single case. future studies should assess a larger volume of individuals of varying races, genders, and lesions that vary in size, location, and depth. abbreviations iron deficiency anemia (ida) quality-switched (q-switched) pulsed dye laser (pdl) conflict of interest disclosures: none funding: none corresponding author: mckenzie a. dirr, ba, bs medical university of south carolina 135 rutledge avenue msc 578 charleston, sc 29425 phone: (843) 792-5858 email: dirr@musc.edu references: 1. heidemeyer k, feldmeyer l, raeber i, dietrich n, cazzaniga s, yawalkar n, et al. successful treatment of iatrogenic cutaneous siderosis with pigment lasers: a retrospective study in 15 consecutive patients. acta derm venereol. 2020, may; 100(10):adv00148. doi:10.2340/000155553503 2. friedrisch jr, cançado rd. intravenous ferric carboxymaltose for the treatment of iron deficiency anemia. rev bras hematol hemoter. 2015;37(6):400-405. doi:10.1016/j.bjhh.2015.08.012 3. nouri k, michael d, kilmer s. lasers in dermatology and medicine [internet]. 1st ed. 2012. london: springer london. 2012. chapter 3, lasers for treatment of vascular lesions. p. 33-43. available from: https://doi.org/10.1007/978-0-85729-281-0. 4. haedersdal m, gniadecka m, efsen j, bechthomsen n, keiding j, wulf hc. side effects from the pulsed dye laser: the importance of skin pigmentation and skin redness. acta https://doi.org/10.1007/978-0-85729-281-0 skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 555 derm venereol. 1998;78(6):445-450. doi:10.1080/000155598442764 5. eklund y, rubin at. laser tattoo removal, precautions, and unwanted effects. curr probl dermatol. 2015;48:88-96. doi:10.1159/000369191 skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 321 brief article tophaceous gout on ear imitating squamous cell carcinoma faraz yousefian, do 1,2, liliana espinoza, bs 3, sarah berger, pa-c 4, sandra osswald, md, faad 5, and frank c. petr, md, faad 3,4 1 university of the incarnate word school of osteopathic medicine, san antonio, tx 2 texas institute for graduate medical education and research 3 long school of medicine, university of texas health san antonio, san antonio, tx 4 audie l. murphy va medical center, san antonio, tx 5 division of dermatology and cutaneous surgery, department of medicine, ut health san antonio, san antonio, tx gout is a common, yet complex form of arthritis that results from the deposition of monosodium urate crystals following normal or increased concentrations of uric acid in the serum. these deposits are most commonly found within joints and typically lead to acute pain and inflammation. tophaceous gout usually presents as smooth, white, or yellow subcutaneous nodules filled with liquid, pasty, or chalky masses which can be deposited in the dermis or connective tissue layer; however, in rare cases the overlying skin can become hyperkeratotic, thus mimicking a squamous cell carcinoma. we present a case of tophaceous gout where the tophus presented on a patient’s superior helix of the ear, clinically mimicking a squamous cell carcinoma. a hispanic 69-year-old immunocompetent man with a past medical history of coronary artery disease, carpal tunnel syndrome, hyperlipidemia, gout, and hypertension presented with a painful lesion on his right ear, which had been actively growing for the past five years. he denied any bleeding or drainage from the area. he also denied any preceding treatment or procedures for this issue. he had fitzpatrick skin type iv with no prior history of skin cancer or other skin disorder. his current medications included atorvastatin, ezetimibe, lisinopril, and meloxicam. he reported that he was treated abstract we report a case of tophaceous gout occurring in a hispanic 69-year-old immunocompetent man. the patient presented with a 0.8 cm pink, purple, and brown dome-shaped papule on the right superior helix of the ear. the lesion was tender to palpitation. a deep shave biopsy was performed and the histological findings demonstrated pseudoepitheliomatous hyperplasia overlying large dermal deposits of pink, hyalinized feathery material surrounded by mild granulomatous inflammation. this finding supported the diagnosis of tophaceous gout rather than the clinical findings imitating squamous cell carcinoma. concurrently, the patient received an intralesional kenalog (ilk) injection to suppress any existing or ensuing inflammation. treatment of the residual lesion was achieved via curettage and electrodesiccation. introduction case report skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 322 for gout in the past with medication, diet, and exercise; however, he was not on any specific medication for gout at the time of presentation. he denied a history of hiv or hepatitis and reported that he quit smoking 40 years prior and only drank alcohol on special occasions. he also denied fever, chills, weight loss, nausea, vomiting, diarrhea, shortness of breath, chest pain, or night sweats. finally, he had no family history of melanoma or other dermatological diseases. physical examination revealed a 0.8 cm pink, purple, and brown dome-shaped papule on the right superior helix of the ear (figure 1). the lesion was tender to palpitation and drainage was observed. cervical lymph node examination did figure 1. physical examination revealed thepresence of a pink, purple, and brown dome-shaped papule approximately 0.8 cm in diameter on the right superior helix of the ear not show any lymphadenopathy. all laboratory findings including uric acid levels were within the normal range. a deep shave biopsy was performed and the histological findings demonstrated pseudoepitheliomatous hyperplasia overlying large dermal deposits of pink, hyalinized feathery material surrounded by mild granulomatous inflammation (figure 2). pas was negative for hyphae. clinical presentation, patient’s past medical history, and histological findings were consistent with gout. concurrently, the patient received an intralesional kenalog (ilk) injection to suppress any existing or ensuing inflammation. treatment of the residual lesion was achieved via curettage and electrodesiccation. figure 2. histological findings showcasing pseudoepitheliomatous hyperplasia overlying large dermal deposits of pink, hyalinized feathery material surrounded by mild granulomatous inflammation. gout is arguably the most common inflammatory arthritis and occurs in approximately 3% of the united states population 1,2. the incidence of gout tends to be higher in adult males and occurs rarely in children. one notable exception is in children carrying inherited defects in the enzymes responsible for metabolizing purine, which subsequently leads to hyperuricemia, or in disorders resulting in impaired renal clearance of uric acid 3. although gout can result from genetic factors, diet is also a paramount contributor given the fact that the incidence of gout continues to rise concomitantly with rising obesity and diabetes rates 4. unsurprisingly, gout is also intimately associated with hypertension and cardiovascular disease— two disease states whose pathogenesis is also exacerbated by obesity and diabetes 4. certain medications such as diuretics, methotrexate, cyclosporine, and etanercept discussion skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 323 have been associated with an increased incidence of tophaceous gout 2,4. the most common pathological feature of gout is the deposition of monosodium urate crystals resulting from chronically high serum levels of urate, otherwise known as hyperuricemia (>6.8 mg/dl) 2. the diagnosis of gout can be verified histologically by the presence of long, needle-shaped crystals of monosodium urate 1,2,4. meanwhile, the clinical manifestation of gout results from activation of the inflammatory response to the urate crystals.2 therapeutic interventions for gout are centered around strategies that promote the dissolution of urate crystals, and effective uric acid management via dietary and lifestyle modifications.4 one of the most effective urate-lowering agents is allopurinol, which typically leads to dramatic reductions in gouty arthritis and tophi. when it comes to acute gout flares, some of the most widely recommended drugs include non-steroidal anti-inflammatory drugs and colchicine.4 other therapeutic avenues can be pursued depending on the location and severity of the lesion. as presented here, deep shave biopsy followed by ilk injections, curettage, and electrodesiccation is an effective treatment option. alternatively, resolution of the residual lesion can also be achieved with excisional surgery. given that gout can be managed or cured by lowering the serum concentration of uric acid below the saturation point of monosodium urate, it is critical that patients are educated about the importance of adhering to the recommended treatment regimen or implementing the appropriate lifestyle and diet modifications.4 this way, they can be better equipped to understand the treatment of their condition and take an active role in preventing the associated comorbidities that dramatically alter their quality of life. conflict of interest disclosures: none funding: none corresponding author: faraz yousefian, do 1515 n main ave apt 2364b san antonio, tx,78212 email : yousefian.faraz@gmail.com references: 1. mueller, k. a., marous, m. r., mannava, k. a. & smith, f. l. tophaceous gout as a squamous cell carcinoma mimicker. jaad case rep 10, 11–13 (2021). 2. dalbeth, n., merriman, t. r. & stamp, l. k. gout. lancet 388, 2039–2052 (2016). 3. cameron, j. s., moro, f. & simmonds, h. a. gout, uric acid and purine metabolism in paediatric nephrology. pediatr nephrol 7, 105– 118 (1993). 4. richette, p. & bardin, t. gout. lancet 375, 318– 328 (2010). conclusion mailto:yousefian.faraz@gmail.com acknowledgements study funded by galderma research & development, snc, and editorial/poster support provided by galderma laboratories, l.p. results subject disposition • 190 subjects (95 subjects per group) were enrolled at 26 sites in the united states and canada and 171 (90%) completed the study (table 1). • subjects were predominantly caucasian (91.1%) and female (72.1%), with a mean age of 49.5 y and a history of chronic rosacea >5 y (70%). efficacy • at week 12 hour 3, the total combined active group receiving the combination of ivm + br showed superior efficacy (iga success 0/1) compared to vehicle (55.8% vs. 36.8%, p = .007; figure 1a). • an advantage for patients receiving br from day 1 was observed, with the ivm+br/12w subgroup showing superior efficacy (61.2% vs. 36.8%, p = .003) at the end of the study and early onset compared to vehicle (figure 1b). • iga change was statistically significant to vehicle in the ivm+br/12w group from week 4 onwards (22.4% at week 4; figure 1b). • at week 12, comparison of the effect of br before and 3h after application showed that, in the ivm+br/12w subgroup, the success rate almost doubled (from 32.7% to 61.2% at hour 0 and hour 3, respectively; figure 1c). • improvements in the ivm+br/12w and ivm+br/8w subgroups compared to the vehicle group were also observed for cea (p < 0.015; figure 2) • after 12 weeks of treatment, 16.3% of subjects in the ivm+br/12w group had 100% reduction in inflammatory lesion count (p = .015 compared to vehicle; figure 3). • a trend towards higher efficacy was observed in the ivm+br/12w compared to the ivm+br/8w subgroup for both outcomes, corroborating the additive effect of br when taken concomitantly with ivm treatment. subject reported outcomes • the subject global improvement of rosacea rate of excellent and good improvement was 77.7%, 66.7%, and 55.2% in the ivm+br/12w, ivm+br/8w, and vehicle groups, respectively. safety • only 8 treatment-related aes in 6 subjects (3.2%) were reported; none were serious or severe. • one related ae leading to discontinuation (allergic dermatitis on the chest) was reported in the ivm+br/8w group. • related worsening of rosacea was observed in similar frequency with 1 (2.2%) ae in the active ivm+br/8w group vs. 3 (2.1%) aes in the vehicle group. introduction • rosacea is often characterized by persistent centrofacial erythema and recurrent inflammatory lesions. • individually, ivermectin 1% (ivm) cream and brimonidine 0.33% (br) gel have been shown to be effective against papules/pustules and persistent facial erythema, respectively, in multiple studies.1,2 • the maximal effect of br on erythema is observable around 3 hours after application. • the objective was to evaluate the efficacy, safety, and patient satisfaction of ivm in combination with br (ivm+br) versus their respective vehicles in subjects with moderate to severe rosacea. methods study design • this multicenter, randomized, double-blind, vehicle-controlled, and parallel group comparison study included subjects with moderate to severe rosacea (investigator global assessment [iga] ≥3, scale 0-4), characterized by persistent diffuse moderate to severe erythema (clinician erythema assessment [cea] ≥3, scale 0-4) and inflammatory lesions (15-70 papules/pustules). treatments • subjects were randomized 1:1:2 into 2 active and 1 double-blind vehicle group. • ivm + br active treatment groups: once-daily ivm and once-daily br for 12 weeks (ivm+br/12w subgroup; n=49) once-daily ivm for 12 weeks and once-daily br vehicle for 4 weeks followed by once-daily br for the remaining 8 weeks (ivm+br/8w subgroup; n=46) • vehicle group: once-daily ivm vehicle and once-daily br vehicle for 12 weeks (vehicle group, n=95). • a daily skin care regimen of gentle cleanser, moisturizing lotion, and facial moisturizer with spf 15 sunscreen was recommended and provided according to established guidelines.3,4 efficacy and safety endpoints • primary endpoint of iga success (0/1, clear/almost clear) on a 5-point scale at week 12, 3 hours after br application. • secondary efficacy endpoints included iga at each visit, cea, 100% reduction in inflammatory lesion count, and subject global improvement of rosacea. • aes were monitored throughout the study. • there was no adjustment of the type i error. concurrent administration of ivermectin 1% cream with brimonidine 0.33% gel improves efficacy and tolerability in the treatment of moderate to severe rosacea linda stein gold, md1; kim papp, md2; charles lynde, md3; edward lain, md4; melinda gooderham, md5; sandra johnson, md6; nabil kerrouche, msc7; gregor schäfer, md8 1department of dermatology, henry ford medical center, detroit, mi, usa; 2k. papp clinical research, probity medical research, waterloo, on, canada; 3lynde institute for dermatology, markham, on, canada; 4austin institute for clinical research, pflugerville, tx; 5skin centre for dermatology, probity medical research and queen’s university peterborough, on, canada; 6johnson dermatology, fort smith, ar; 7galderma r&d, sophia antipolis, france; 8galderma international, paris, france soo.p-rd105069-02 summary • simultaneous administration of ivm 1% cream with br 0.33% gel demonstrated superior efficacy compared to their respective vehicles for the treatment of moderate to severe rosacea. • early introduction of br (from day 1), along with a complete daily skin care regimen, may exert additional efficacy benefit and accelerate treatment success without impairing tolerability. • the ivm + br association was well tolerated, with less than 5% related aes. • this regimen is a promising option for the comprehensive management of this complex disease. references 1. stein l, kircik l, fowler j, et al. efficacy and safety of ivermectin 1% cream in treatment of papulopustular rosacea: results of two randomized, double-blind, vehicle-controlled pivotal studies. j drugs dermatol. 2014;13:316-323. 2. fowler j jr, jackson m, moore a, et al. efficacy and safety of once-daily topical brimonidine tartrate gel 0.5% for the treatment of moderate to severe facial erythema of rosacea: results of two randomized, double-blind, and vehicle-controlled pivotal studies. j drugs dermatol. 2013;12:650-656. 3. del rosso jq. understanding skin cleansers and moisturizers: the correlation of formulation science with the art of clinical use. j cosmet dermatol. 2003;16:19-31. 4. schaller m, almeida l, bewley a, et al. rosacea treatment update: recommendations from the global rosacea consensus (rosco) panel. br j dermatol. 2016;176:465-471. figure 1. investigator global assessment success (itt-locf) 40.7 success 15.1 29.3 29.5 25.6 39.0 45.5 29.1 24.4 20.527.9 7.3 4.5 2.3 0 0 0 10 20 30 40 50 60 70 80 90 100 vehicles ivm + br / 8 weeks ivm + br / 12 weeks 0 = clear 1 = almost clear 2 = mild erythema 3 = moderate erythema 4 = severe erythema 68.3* success 75.0* success *p = .007 pe rc en t o f s ub jec ts 4.2 6.5 16.3 0 2 4 6 8 10 12 14 16 18 vehicles ivm + br / 8 weeks ivm + br / 12 weeks pe rc en t o f s ub je cts w ith 1 00 % r ed uc tio n in in fla m m at or y l es io n co un t p = .015 figure 2. clinician erythema assessment at week 12/hour 3 (itt-locf) figure 3. percentage of subjects with 100% reduction in inflammatory lesion count (ilc) at hour 3 week 12 (itt-locf) almost clear clear 2.1 (n = 2) 13.7 (n = 13) 34.7 (n = 33) 42.1 (n = 40) 0 10 20 30 40 50 60 vehicles (ivm + br) total active ivm + br 36.8 (n = 35) 55.8* (n = 53) *p = .007 pe rce nt o f s ub je cts a) at week 12/hour 3 4.1 22.4 42.9 61.2 4.3 13.0 30.4 50.0 5.3 9.5 24.2 36.8 0 10 20 30 40 50 60 70 baseline week 4 week 8 week 12 pe rce nt o f s ub je cts a ch ie vin g ig a su cce ss (i ga 0 o r 1 ) ivm+br/12w (n = 46) ivm+br/8w (br vehicle) vehicle (n = 95) ivm+br/8w (br active) p = .003 p = .02 p = .04 (n = 49) b) percent of subjects achieving success with ivm+br/12w, ivm+br/8w, or vehicle 4.3 10.9 8.2 16.3 23.9 39.1 24.5 44.9 0 10 20 30 40 50 60 70 ivm + br / 8 weeks hour 0 ivm + br / 8 weeks hour 3 ivm + br / 12 weeks hour 0 ivm + br / 12 weeks hour 3 iga 0 iga 1 su cc es s r at e ( pe rc en t o f s ub jec ts wi th a n ig a of 0 o r 1 ) 28.3% 50.0% 32.7% 61.2% c) at week 12/hour 0 versus week 12/hour 3 (before versus after application of br) active group vehicle group ivm+br/8w ivm+br/12w subjects, n (%) 46 (100) 49 (100) 95 (100) completed, n (%) 41 (89.1) 44 (89.8) 86 (90.5) discontinued, n (%) 5 (10.9) 5 (10.2) 9 (9.5) adverse event, possibly related 1 (2.2) 0 1 (1.1) subject’s request 4 (8.7) 1 (2.0) 3 (3.2) lost to follow-up 0 3 (6.1) 3 (3.2) other 0 1 (2.0) 2 (2.1) table 1. subject disposition fc17postergaldermasteingoldconcurrentadministration.pdf skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 649 in-depth review neonatal lupus erythematosus: a case report and review of the literature taylor bullock, md1, robert simonds, md1, jeffrey mcbride, md2, mawish irfan, md1, sarah young, md1 1 department of dermatology, cleveland clinic foundation, cleveland, oh 2 department of dermatology, university of oklahoma health sciences center, oklahoma city, ok a 3-month-old female patient with a past medical history of premature birth (34 weeks) and intrauterine growth restriction, initially presented to the emergency department due to concern over poor feeding and labored breathing. while in the ed, the patient arrested, requiring cardiopulmonary resuscitation and intubation, and was subsequently admitted to the intensive care unit. the patient’s presenting symptoms were accompanied by a rash which had appeared following minimal sun exposure 6 weeks prior to presentation. the patient had no family history of diagnosed autoimmune disorders, although the mother experienced a facial rash during pregnancy and had a history of recurrent miscarriages, frequent dental caries, and chronic dry eyes, consistent with sjogren's syndrome-like symptoms. physical examination was remarkable for thin scaly pink annular papules and plaques on the scalp, forehead, malar cheeks, arms, trunk, and extremities (figure 1). a punch biopsy demonstrated vacuolar interface dermatitis, dyskeratosis, and focally increased mucin (figure 2 & 3). lab work was remarkable for the presence of anti-ssa and anti-ssb antibodies, as well as elevated anticardiolipin and b2 glycoprotein antibodies. the histologic findings and laboratory abnormalities confirmed the diagnosis of neonatal lupus erythematosus. increased levels of alanine transaminase (60, normal range 0-40 u/l) and aspartate transaminase (97, normal range 1-40] u/l) were also present. ultrasound of the head showed enlargement of extra-axial csf spaces, with subsequent ct imaging of the brain noted widened subarachnoid space, diffuse white matter atrophy and chronic bilateral hygromas. these findings were confirmed with an mri of the brain, which abstract neonatal lupus erythematosus (nle) is a rare autoimmune condition caused by transplacental passage of maternal igg autoantibodies to the fetus. it often presents with erythematous annular lesions on the scalp and periorbital area that appear after exposure to sunlight. clinicians should be aware of the broad manifestations of neonatal lupus erythematosus, including cutaneous, cardiac, hematologic, hepatic and neurological manifestations. we present a case of cutaneous neonatal lupus erythematosus with rare central nervous system findings and perform a literature review on the subject. case report skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 650 revealed volume loss of both grey and white matter, widened subarachnoid space and bilateral subdural collections. brain myelination was found to be normal for the patient’s age and no evidence of vasculopathy was found. further workup for menke’s disease and glutaric aciduria was negative. a neonatal crisis panel showed no genetic abnormalities, though an inherited variant of uncertain significance in the igf1r gene was found. no evidence of arrhythmia or conduction disease on ecg or telemetry were found, and an ophthalmological exam which showed no inflammation of the optic nerve. figure 1. thin scaly pink annular papules and plaques on the scalp, forehead, malar cheeks, arms, trunk, and extremities figure 2. vacuolar interface dermatitis, dyskeratosis, and focally increased mucin figure 3. closer view of punch biopsy neonatal lupus erythematosus (nle) is an autoimmune disease caused by transplacental passage of maternal igg autoantibodies against intracellular ribonucleoproteins ro (ssa) and/or la (ssb) to the fetus. the pathogenesis of nle is unclear, although evidence suggests the maternal antibodies bind to specific cells in neonatal organs and cause inflammation. the inflammation can progress to fibrosis and calcification, especially in the conduction system of the heart.1 the passive antibodies neonatal lupus erythematosus skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 651 are most frequently associated with maternal systemic lupus erythematosus (sle) or sjogren’s syndrome, but are often present in the absence of maternal autoimmune disease or autoimmune-like symptoms.2 approximately 50% of asymptomatic mothers with these autoantibodies end up developing symptoms suggestive of autoimmune disease within years of delivery, with the most common symptoms being dry eyes, dry mouth, raynaud’s syndrome, or rashes.3 nle most commonly causes cutaneous and cardiac manifestations, though hepatic,4 neurologic,5 and hematologic6 manifestations have been described. complete heart block is a serious complication of nle that can develop before or after the time of diagnosis.7,8 most clinical manifestations of the disease progressively resolve as the transferred maternal antibodies are cleared and disappear 6-9 months after birth.9,10 after excluding conditions that present similarly, the diagnosis of nle is established when compatible clinical manifestations and anti-ro (ssa), anti-la (ssb), or antiribonucleoprotein (rnp) antibodies are present. the anti-ro (ssa) antibody targets proteins of the ro family, namely ro52 and ro60. ro52 is a regulatory protein that negatively moderates the inflammatory response. acting separately from ro52, ro60 regulates the fate of misfolded rna within cells.11 the anti-la (ssb) antibody targets the la protein, which is involved in numerous aspects of rna metabolism.12,13 cases of nle with anti-u1 rnp (small nuclear ribonucleoproteins) antibodies and no anti-ro (ssa) or anti-la (ssb) have been reported and typically present with cutaneous findings and lack cardiac manifestations.14,15 the cutaneous manifestations of nle commonly involve erythematous annular lesions or arcuate macules with slight central atrophy and raised active margins with a predilection for the scalp and periorbital area (figure 1).16 the distinctive periorbital distribution is often described as an ‘owl eye’ or ‘eye mask’ appearance.17 the lesions occasionally exhibit scaling and sometimes affect the palms, soles, or diaper area.18,19 cutaneous manifestations may be present at delivery but are most often observed after exposure to ultraviolet light anywhere from a few days to weeks after birth.20 though uncommon, prominent lesions may undergo blistering or crusting. lesions are typically nonscarring and remain for a few weeks to months before resolving, though atrophic lesions may persist even after the levels of maternal antibodies have fallen.17 approximately 10% of nle patients may exhibit telangiectasia on the face or genitals between 6 and 12 months of age.21 the polycyclic skin lesions of nle can present similarly to urticaria, tinea corporis, seborrheic dermatitis, annular erythemas of childhood, langerhans cell histiocytosis, and autoinflammatory syndromes. urticarial lesions are raised, pruritic, and erythematous, and can be distinguished from nle lesions by their transient nature and raised centers. in contrast to urticarial lesions, nle lesions tend to have atrophied center.22 lesions of nle can be distinguished from tinea corporis by having less scale and absent fungal hyphae on a potassium hydroxide (koh) preparation of skin scrapings.22 in addition to its typical manifestation of non-inflammatory greasy yellow scales on the scalp, informally referred to as “cradle cap,” seborrheic dermatitis can manifest as yellow greasy scales on the face that are accompanied by erythematous, scaly, salmon-colored plaques. the latter manifestation may appear similarly to nle lesions, though nle lesions are less scaly and darker purple in color.22,23 skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 652 annular erythemas of childhood are rare diseases such as erythema annulare centrifugum, familial annular erythema, erythema multiforme, and annular erythema of infancy. these diseases can be differentiated from cutaneous nle by their migrating course, lack of central atrophy, presence of peripheral lesions, long duration, and unusual history of new lesion development after the disappearance of lesions at different locations.24 langerhans cell histiocytosis may present with pustular, purpuric, petechial, vesicular, or papulonodular lesions, and may appear similar to those of nle. the majority of patients with langerhans cell histiocytosis are found to have multi-system disease affecting the liver, spleen, and/or bone. additionally, skin biopsy will distinguish lesions of langerhans cell histiocytosis from those of nle.22,25 autoinflammatory diseases may closely resemble cutaneous nle manifestations, but commonly present with multisystem involvement and severe fevers. autoinflammatory diseases most likely to resemble nle include stimulator of interferon genes (sting)-associated vasculopathy with onset in infancy (savi), chronic atypical neutrophilic dermatitis with lipodystrophy and elevated temperature syndrome (candle syndrome), autoinflammation and plcg2associated antibody deficiency and immune dysregulation (aplaid), and c1q deficiency.22,26 the histopathological findings of nle skin lesions commonly resemble those of subacute cutaneous lupus erythematosus and include vacuolar alterations at the dermo-epidermal interface and adnexal structures.27 urticaria-like lesions that have superficial and deep perivascular and periadnexal lymphocytic infiltrates can also occur.27 hepatic manifestations of nle range from liver failure and hepatitis to asymptomatic elevated liver enzymes, cholestasis, and mild hepatosplenomegaly.4,17 hyperbilirubinemia and increased liver transaminases can occasionally be the only presentation of nle.28 when nle causes liver failure in utero or at birth, the clinical presentation is similar to that of neonatal storage disease or neonatal hemochromatosis.17 hepatic manifestations other than liver failure are associated with a good prognosis and undergo spontaneous resolution with no long-term sequelae.17 though uncommon, neurologic manifestations of nle such as hydrocephalus and macrocephaly have been described.5 imaging with ct scans has shown that infants with nle can have reduced attenuation of white matter, increased subarachnoid space, ventriculomegaly, and basal ganglia calcifications, with normal grey matter.2,29 there is currently no literature on brain mris in infants with nle.2 a case of abnormal periventricular white matter signals on mri. in a patient with a history of nle has been reported, though the patient was 3 years old.30 transient and permanent vasculopathies of the central nervous system due to nle have also been reported, though these findings are less common.31 despite ct findings, clinical findings of neurologic disease are typically absent, though spastic paraparesis, myelopathy, focal seizure, and hydrocephalus have been reported.2,30 the neurological imaging findings in our patient are unique because volume loss of grey matter was present, in addition to the previously reported findings of white matter volume loss, widened subarachnoid space, and bilateral subdural collections on imaging. skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 653 the mechanism for these subclinical central nervous system findings remains unclear, but it is likely a transient phenomenon that occurs due to maternal antibodies.30 congenital heart block is a well-known and serious complication of nle, as the mortality rate for complete congenital heart block is 4% to 29%.32,33 in fact, many cases of nle are diagnosed after noting bradycardia in the fetus or newborn.1 heart block, which occurs due to autoimmune injury and secondary fibrosis of the atrioventricular (av) node and its surrounding tissue, usually happens in utero during the second or third trimester. cases of firstor second-degree heart block progressing to complete heart block have been reported.34 while non-cardiac manifestations of nle are generally transient and fade as maternal antibodies are cleared from the blood, the effects on the conduction system are permanent. approximately twothirds of patients with autoimmune congenital heart block receive a pacemaker before reaching adulthood.35 though congenital heart block is the most widely recognized cardiac manifestation of nle, many other cardiac manifestations have been recognized. these other cardiac manifestations include diffuse myocardial disease, structure defects, and other electrophysiologic anomies.32 diffuse myocardial disease can occur with or without conduction disturbances, suggesting it may be a separate manifestation from the congenital heart block manifestation of nle.36 while heart block is often diagnosed before or at birth, myocardial disease may not be detected until months or years after birth.17 the clinical symptoms of diffuse myocardial disease may be severe enough to persist despite pacemaker therapy and can lead to heart failure, death, or transplantation.37,38 structural congenital heart defects, including patent ductus arteriosus, atrial and ventricular septal defects, and semilunar and atrioventricular valvular abnormalities, have been reported to occur in 16-42% of patients with congenital heart block.39,40 additional electrophysiological abnormalities include transient and persistent sinus node dysfunction, prolonged qt interval, ventricular and junctional tachycardia, and atrial flutter.37,41 typical hematological manifestations of nle include anemia, neutropenia, or thrombocytopenia.6 the incidence of hematological manifestations of nle may be underestimated, as it is not routine for healthy infants to undergo complete blood counts. thrombocytopenia is the most common hematological manifestation, which occurs in at least 10% or cases.42 the thrombocytopenia is transient and typically of no clinical importance, though one case of gastrointestinal bleeding had been attributed to nle-associated thrombocytopenia in 1999.43 neutropenia is less commonly reported and may be associated specifically with the anti-ro (ssa) antibody.44 of note, no cases of neonatal sepsis occurred in the children with neutropenia.9 a few cases of pancytopenia have also been reported.45,46 neonatal lupus erythematosus (nle) is an autoimmune disorder caused by the transplacental passage of maternal antissa/ssb antibodies to the fetus. nle frequently demonstrates cutaneous and cardiac manifestations, although clinicians should be aware of hematologic, hepatic, and neurologic manifestations. most clinical manifestations of nle progressively resolve as the maternal antibodies are cleared and tend to disappear 6-9 months after birth (with the exception of congenital heart block). ct conclusion skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 654 imaging of infants with nle has demonstrated attenuation of white matter, increased subarachnoid space, ventriculomegaly, and basal ganglia calcifications with normal grey matter. mri performed on our patient revealed unique findings of grey matter volume loss in addition to bilateral subdural collections. while the significance of these mri findings is unknown at this point, serial mris in the future may clarify potential implications. conflict of interest disclosures: none funding: none corresponding author: taylor bullock, md department of dermatology cleveland clinic foundation 9500 euclid ave cleveland, oh 44195 email: bulloct3@ccf.org references: 1. friedman d, duncanson l, glickstein j, buyon j. a review of congenital heart block. images paediatr cardiol. jul 2003;5(3):3648. 2. chen cc, lin kl, chen cl, wong am, huang jl. central nervous system manifestations of neonatal lupus: a systematic review. lupus. dec 2013;22(14):1484-8. doi:10.1177/0961203313509294 3. rivera tl, izmirly pm, birnbaum bk, et al. disease progression in mothers of children enrolled in the research registry for neonatal lupus. ann rheum dis. jun 2009;68(6):828-35. doi:10.1136/ard.2008.088054 4. shahian m, khosravi a, anbardar mh. early cholestasis in neonatal lupus erythematosus. ann saudi med. jan-feb 2011;31(1):80-2. doi:10.4103/0256-4947.70569 5. boros ca, spence d, blaser s, silverman ed. hydrocephalus and macrocephaly: new manifestations of neonatal lupus erythematosus. arthritis rheum. mar 15 2007;57(2):261-6. doi:10.1002/art.22543 6. lee la. transient autoimmunity related to maternal autoantibodies: neonatal lupus. autoimmun rev. apr 2005;4(4):207-13. doi:10.1016/j.autrev.2004.11.003 7. izmirly pm, saxena a, sahl sk, et al. assessment of fluorinated steroids to avert progression and mortality in anti-ssa/roassociated cardiac injury limited to the fetal conduction system. ann rheum dis. jun 2016;75(6):1161-5. doi:10.1136/annrheumdis-2015-208311 8. izmirly pm, saxena a, kim my, et al. maternal and fetal factors associated with mortality and morbidity in a multi-racial/ethnic registry of anti-ssa/ro-associated cardiac neonatal lupus. circulation. nov 1 2011;124(18):1927-35. doi:10.1161/circulationaha.111.033894 9. cimaz r, spence dl, hornberger l, silverman ed. incidence and spectrum of neonatal lupus erythematosus: a prospective study of infants born to mothers with anti-ro autoantibodies. j pediatr. jun 2003;142(6):678-83. doi:10.1067/mpd.2003.233 10. vanoni f, lava sag, fossali ef, et al. neonatal systemic lupus erythematosus syndrome: a comprehensive review. clin rev allergy immunol. dec 2017;53(3):469476. doi:10.1007/s12016-017-8653-0 11. strandberg l, salomonsson s, bremme k, sonesson s, wahren-herlenius m. ro52, ro60 and la igg autoantibody levels and ro52 igg subclass profiles longitudinally throughout pregnancy in congenital heart block risk pregnancies. lupus. 2006;15(6):346-53. doi:10.1191/0961203306lu2309oa 12. yoshimi r, ueda a, ozato k, ishigatsubo y. clinical and pathological roles of ro/ssa autoantibody system. clin dev immunol. 2012;2012:606195. doi:10.1155/2012/606195 13. gleicher n, elkayam u. preventing congenital neonatal heart block in offspring of mothers with anti-ssa/ro and ssb/la antibodies: a review of published literature and registered clinical trials. autoimmun rev. sep 2013;12(11):1039-45. doi:10.1016/j.autrev.2013.04.006 14. provost tt, watson r, gammon wr, radowsky m, harley jb, reichlin m. the neonatal lupus syndrome associated with u1rnp (nrnp) antibodies. n engl j med. apr 30 1987;316(18):1135-8. doi:10.1056/nejm198704303161807 15. sheth ap, esterly nb, ratoosh sl, smith jp, hebert aa, silverman e. u1rnp positive skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 655 neonatal lupus erythematosus: association with anti-la antibodies? br j dermatol. apr 1995;132(4):520-6. doi:10.1111/j.13652133.1995.tb08705.x 16. shiiya c, ota m. facial rash, fever, and anemia in a newborn. jama. may 23 2017;317(20):2125-2126. doi:10.1001/jama.2017.3058 17. lee la. neonatal lupus: clinical features and management. paediatr drugs. 2004;6(2):718. doi:10.2165/00148581-200406020-00001 18. sommer ll, manders sm. seeing double: annular diaper rash in twins. pediatr dermatol. may-jun 2015;32(3):410-3. doi:10.1111/pde.12508 19. see a, wargon o, lim a, sugo e, le k. neonatal lupus erythematosus presenting as papules on the feet. australas j dermatol. aug 2005;46(3):172-6. doi:10.1111/j.14400960.2005.00173.x 20. silverman e, jaeggi e. non-cardiac manifestations of neonatal lupus erythematosus. scand j immunol. sep 2010;72(3):223-5. doi:10.1111/j.13653083.2010.02443.x 21. guinovart rm, vicente a, rovira c, suñol m, gonzález-enseñat ma. facial telangiectasia: an unusual manifestation of neonatal lupus erythematosus. lupus. apr 2012;21(5):5525. doi:10.1177/0961203311430701 22. silverman e. neonatal lupus. in: textbook of pediatric rheumatology, cassidy jt, petty re (eds), wb saunders, philadelphia 2001. p.456. 23. savino f, viola s, tarasco v, locatelli e, ricagni a, coppo p. neonatal lupus erythematosus: a cutaneous cases based update. ital j pediatr. jan 7 2016;42:1. doi:10.1186/s13052-015-0208-5 24. baselga e, torrelo a. inflammatory and purpuric eruptions. neonatal dermatology. copyright © 2008 elsevier inc. all rights reserved.; 2008:311-42. 25. lau l, krafchik b, trebo mm, weitzman s. cutaneous langerhans cell histiocytosis in children under one year. pediatr blood cancer. jan 2006;46(1):66-71. doi:10.1002/pbc.20479 26. bonnekoh h, butze m, kallinich t, kambe n, kokolakis g, krause k. spectrum of genetic autoinflammatory diseases presenting with cutaneous symptoms. acta derm venereol. mar 25 2020;100(7):adv00091. doi:10.2340/00015555-3427 27. peñate y, guillermo n, rodríguez j, et al. histopathologic characteristics of neonatal cutaneous lupus erythematosus: description of five cases and literature review. j cutan pathol. jun 2009;36(6):660-7. doi:10.1111/j.1600-0560.2008.01136.x 28. tahernia l, alimadadi h, tahghighi f, amini z, ziaee v. frequency and type of hepatic and gastrointestinal involvement in juvenile systemic lupus erythematosus. autoimmune dis. 2017;2017:8097273. doi:10.1155/2017/8097273 29. zuppa aa, riccardi r, frezza s, et al. neonatal lupus: follow-up in infants with antissa/ro antibodies and review of the literature. autoimmun rev. apr 2017;16(4):427-432. doi:10.1016/j.autrev.2017.02.010 30. prendiville js, cabral da, poskitt kj, au s, sargent ma. central nervous system involvement in neonatal lupus erythematosus. pediatr dermatol. jan-feb 2003;20(1):60-7. doi:10.1046/j.15251470.2003.03014.x 31. saini ag, sankhyan n, bhattad s, vyas s, saikia b, singhi p. cns vasculitis and stroke in neonatal lupus erythematosus: a case report and review of literature. eur j paediatr neurol. may 2014;18(3):444-8. doi:10.1016/j.ejpn.2014.01.007 32. capone c, buyon jp, friedman dm, frishman wh. cardiac manifestations of neonatal lupus: a review of autoantibodyassociated congenital heart block and its impact in an adult population. cardiol rev. mar-apr 2012;20(2):72-6. doi:10.1097/crd.0b013e31823c808b 33. balmer c, fasnacht m, rahn m, molinari l, bauersfeld u. long-term follow up of children with congenital complete atrioventricular block and the impact of pacemaker therapy. europace. oct 2002;4(4):345-9. doi:10.1053/eupc.2002.0266 34. askanase ad, friedman dm, copel j, et al. spectrum and progression of conduction abnormalities in infants born to mothers with anti-ssa/ro-ssb/la antibodies. lupus. 2002;11(3):145-51. doi:10.1191/0961203302lu173oa 35. friedman dm, rupel a, glickstein j, buyon jp. congenital heart block in neonatal lupus: the pediatric cardiologist's perspective. indian j pediatr. jun 2002;69(6):517-22. doi:10.1007/bf02722656 36. nield le, silverman ed, smallhorn jf, et al. endocardial fibroelastosis associated with maternal anti-ro and anti-la antibodies in the absence of atrioventricular block. j am skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 656 coll cardiol. aug 21 2002;40(4):796-802. doi:10.1016/s0735-1097(02)02004-1 37. hornberger lk, al rajaa n. spectrum of cardiac involvement in neonatal lupus. scand j immunol. sep 2010;72(3):189-97. doi:10.1111/j.1365-3083.2010.02437.x 38. jaeggi et, hamilton rm, silverman ed, zamora sa, hornberger lk. outcome of children with fetal, neonatal or childhood diagnosis of isolated congenital atrioventricular block. a single institution's experience of 30 years. j am coll cardiol. jan 2 2002;39(1):130-7. doi:10.1016/s07351097(01)01697-7 39. llanos c, izmirly pm, katholi m, et al. recurrence rates of cardiac manifestations associated with neonatal lupus and maternal/fetal risk factors. arthritis rheum. oct 2009;60(10):3091-7. doi:10.1002/art.24768 40. eronen m, sirèn mk, ekblad h, tikanoja t, julkunen h, paavilainen t. shortand longterm outcome of children with congenital complete heart block diagnosed in utero or as a newborn. pediatrics. jul 2000;106(1 pt 1):86-91. doi:10.1542/peds.106.1.86 41. zhao h, cuneo bf, strasburger jf, huhta jc, gotteiner nl, wakai rt. electrophysiological characteristics of fetal atrioventricular block. j am coll cardiol. jan 1 2008;51(1):77-84. doi:10.1016/j.jacc.2007.06.060 42. watson r, kang je, may m, hudak m, kickler t, provost tt. thrombocytopenia in the neonatal lupus syndrome. arch dermatol. apr 1988;124(4):560-3. 43. lee l. neonatal lupus erythematosus and congenital heart block. in: dyall-smith d, marks r, editors. dermatology at the millennium: the proceedings of the 19th world congress of dermatology. london: the parthenon publishing group, 1999: 2737. 44. kurien bt, newland j, paczkowski c, moore kl, scofield rh. association of neutropenia in systemic lupus erythematosus (sle) with anti-ro and binding of an immunologically cross-reactive neutrophil membrane antigen. clin exp immunol. apr 2000;120(1):209-17. doi:10.1046/j.1365-2249.2000.01195.x 45. lynn cheng c, galbraith s, holland k. congenital lupus erythematosus presenting at birth with widespread erosions, pancytopenia, and subsequent hepatobiliary disease. pediatr dermatol. jan-feb 2010;27(1):109-11. doi:10.1111/j.15251470.2009.01057.x 46. wang l-j, yang y-h, lin m-i, chiang b-l, mu s-c. neonatal lupus erythematosus with recurrent pancytopenia: a case report. journal of microbiology, immunology, and infection = wei mian yu gan ran za zhi. 2002/12// 2002;35(4):262-264. skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 324 brief article a novel case of eruptive keratoacanthomas associated with apalutamide treatment for prostate cancer natasha baah, do1, george skandamis, md2 1 department of family medicine, holzer health system, gallipolis, oh 2 universal dermatology & vein care, columbus, oh prostate cancer is the second most common cancer globally diagnosed in men1, with more than 160,000 new cases each year in the united states.2 even with relatively high rates of survival, many deaths occur due to metastases. it most often metastasizes to bone, to other sites including lymph nodes, lungs, and liver as well.1,3 a wide range of treatment options are currently available — active surveillance, surgery, radiation, chemotherapy, and hormonal therapeutics.2 although most patients experience remission with standard therapy, approximately 10-20% of prostate cancer cases are castrationresistant.4 up to 16% of these patients show no evidence that the cancer has spread at the time of the castration-resistant diagnosis.4 castration-resistance refers to continued tumor growth despite appropriate hormonal treatment. in february 2018, apalutamide, a nonsteroidal antiandrogen (nsaa), was approved by the food and drug administration (fda) as the first drug for nonmetastatic castration-resistant prostate cancer.4 recently, there have been cases reporting generalized eruptive keratoacanthomas (eka) in association with use of the program cell death (pd-1) targeting drugs like nivolumab, pembrolizumab, and leflunomide when treating malignancy. 5,6,7 however, based on our literature review, we were unable to find documented cases involving apalutamide. we present the case of an 86-year-old caucasian male with castration-resistant prostate cancer following radical prostatectomy diagnosed with biopsyconfirmed eka with squamous cell carcinoma (scc) two and a half months after the initiation of apalutamide. abstract recently, there have been cases reporting generalized eruptive keratoacanthomas (eka) in association with use of the program cell death (pd-1) targeting drugs like nivolumab, pembrolizumab, and leflunomide when treating malignancy. however, based on our literature review, we were unable to find documented cases involving apalutamide. we present the case of an 86-year-old caucasian male with castration-resistant prostate cancer following radical prostatectomy diagnosed with biopsy-confirmed eka with squamous cell carcinoma (scc) two and a half months after the initiation of apalutamide. introduction case report skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 325 the patient is an 86-year-old caucasian male who presented with skin lesions that were rapidly enlarging, dome-shaped nodules with central hyperkeratotic depressed cores that resembled volcanos located on the left forearm and bilateral lower extremities (figure 1a, 1b). patient stated that the lesions had been there for two and a half months and that he had not received any treatment for them. he has no family history of non-melanoma skin cancer or melanoma. past medical history is significant for squamous cell skin cancer on the left central forehead and prostate cancer, for which he underwent a radical prostatectomy 25 years ago. the patient indicated that he was never told the stage of his prostate cancer. he remained symptom free until 2013 when a yearly physical indicated subsequent rising prostate specific antigen (psa) levels. the patient was placed on leuprolide acetate for two years. psa levels showed a promising decrease but were not satisfactory given patient history of prostatectomy. in april 2018, the patient was transitioned to apalutamide 240 mg (four 60mg tablets). one month later, the patient began experiencing a mild, but non-bothersome, pruritus sensation bilaterally on his legs, followed by a slowly developing rash that was not initially biopsied during month three, the same lesions dramatically erupted on both his arms and legs with greater intensity described as moderate and bothersome. simultaneously, the patient was informed that his psa levels were starting to rise once again. by month four, apalutamide was discontinued, and the patient was referred to dermatology for evaluation of the eruptive rash, that had decreased in intensity. it is worth noting that trauma from the various levels of the itchscratch cycle could have played a role in precipitating his lesions. although based on how the patient recollected the events, we do not believe that the trauma inflicted would have been significant enough to cause the presenting rash. reports in the literature have described apalutamide-related dermatological adverse events consisting of maculopapular rashes (33.8%) and xerosis (32.4%) 11, toxic epidermal necrolysis (ten), and psoriatic skin lesions, lichenoid drug eruptions, and urticaria.12 in august 2018, the patient presented to dermatology for the initial consultation (figure 1a, 1b). the given clinical history made a drug reaction highly probable for causing the presenting rash. shave biopsies showed well-differentiated squamous cell carcinoma with keratoacanthoma-type features. the left proximal pre-tibial region, left distal calf, and left distal dorsal forearm lesions showed crateriform invagination of the epidermis containing atypical squamous cells with eosinophilic cytoplasm. the right and left distal calves and right proximal dorsal forearm showed dermal lobules of mildly atypical squamous cells with identifiable intercellular bridges and areas of keratinization. the treatment regimen consisted of the discontinuation of apalutamide; triamcinolone acetonide 0.1% topical steroid cream to be applied twice daily on affected areas to reduce the swelling, itching, and redness; and topical calcipotriene cream (for the plaque-like lesions) combined with 5-fluorouracil cream (for the acanthosis) applied once daily for seven to ten days. mohs surgery was utilized for the removal of the tumor lesions over the next several months. by october, the lesions showed significant improvement from initial presentation (figure 2). we did not consider restarting apalutamide due to limited knowledge on the pathogenesis and patient dissatisfaction with alternatives as documented in recent studies. skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 326 figure 1. initial consultation, three months after the initiation of apalutamide – august 2018 apalutamide is an nsaa approved for the treatment of non-metastatic castrationresistant prostate cancer since 2018.3 apalutamide induces a therapeutic effect through the competitive antagonism of the androgen receptor at the androgen binding site. cell growth gene transcription is inhibited through inactivation of the receptor causing prostatic cells to undergo apoptosis leading to effectiveness in refractory prostate cancers.3 the patient presented with initial eruptive keratoacanthomas one month after the addition of apalutamide 240 mg daily with subsequent full onset of the lesions by month two. keratoacanthomas (ka) are rapidly growing, self-resolving, atypical squamous cell proliferations that can be considered a lowgrade squamous cell carcinoma (scc).6,8 because distinguishing kas from invasive scc can be difficult, they are often treated as if they are malignant neoplasms. 8 ka lesions appear in solitude secondary to an array of causes or multiple may arise in a generalized distribution as a manifestation of a syndrome.2,3 eruptive ka (eka) lesions are distinguished from those associated with syndromes by rapid onset and decreased duration of eka lesion presence. eka is a rare variant of multiple kas affecting the skin and mucous membranes first described in 1950 as the relative sudden onset of severely pruritic, numerous small flesh-colored follicular papules 1-3 mm in diameter, with central keratin centers, papillomatosis, acanthosis, and glassy eosinophilic hyaline keratinocytes.9,10 although there is a well-established correlation with immunosuppression and squamous cell carcinoma, a link has not been determined between immunosuppression and eruptive keratoacanthomas. figure 2. follow up with treatment regimen topical triamcinolone acetonide 0.1% cream, topical calcipotriene cream combined with 5-fluorouracil, and mohs surgery october 2018. the patient described had previous medical history of squamous cell carcinoma, which could increase his predisposition to developing eka. in patients treated with immunomodulators previously described, the discussion conclusion skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 327 eruptive keratoacanthomas resolved with the discontinuation of the medication and systemic retinoids. however, treatment of eruptive keratoacanthomas is not limited to retinoids and may include surgical removal, cyclophosphamide10, or intralesional corticosteroids. the patient in this case showed successful treatment with combination therapy of triamcinolone acetonide 0.1% and calcipotriene combined with 5-fluorouracil cream. the mechanism of apalutamide-induced eruptive keratoacanthomas has yet to be elicited but shows a potential correlation evident in this patient. abbreviation and acronym list eka = eruptive keratoacanthomas fda = food and drug administration ka = keratoacanthomas nsaa = nonsteroidal antiandrogen pd-1 = program cell death psa = prostate specific antigen scc = squamous cell carcinoma conflict of interest disclosures: none funding: none corresponding author: george skandamis, md, faad universal dermatology & vein care 425 metro place north suite 195 dublin, oh 43017 office phone: (614)706-3057 email: gskandamis@gmail.com references: 1. merriel sw, funston g, & hamilton w. prostate cancer in primary care. adv ther. 2018; 35(9): 1285–1294. doi: 10.1007/s12325018-0766-1. 2. litwin ms & tan hj. the diagnosis and treatment of prostate cancer: a review. jama. 2017; 317(24):2532-2542. doi:10.1001/jama.2017.7248. 3. smith mr, saad f, chowdhury s, oudard s, hadaschik ba, grff jn, olmos d, mainwaring pn, lee jy, uemura h, lopez-gitliz a, & trudel gc. apalutamide treatment and metastasis-free survival in prostate cancer. n engl j med. 2018; 378(15):1408-1418. doi: 10.1056/nejmoa1715546. 4. fda updates. new non-metastatic, castrationresistant prostate cancer treatment. onc times. 2018; 40(6):17. doi: 10.1097/01.cot.0000531953.43104.c7. 5. bednarek r, marks k, lin g. eruptive keratoacanthomas secondary to nivolumab immunotherapy. int j dermatol. 2018; 57(3):e28e29. doi: 10.1111/ijd.13893. 6. freites-martinez a, kwong by, rieger ke, coit dg, colevas ad, lacouture me. eruptive katoacanthomas associated with pembrolizumab therapy. derm. 2017; 153(7):694-697. doi: 10.1001/jamadermatol.2017.0989. 7. tidwell wj, malone j, callen jp. eruptive keratoacanthomas associated with leflunomide letters. derm. 2016; 152(1):105-106. doi: 10.1001/jamadermatol.2015.2506. 8. kwiek b, schwartz ra. keratoacanthoma: an update and review. j amer acad dermatol. 2016; 74(6):1220-1233. 9. nofal a, assaf m, nofal e, alradi m. generalized eruptive keratoacanthoma: proposed diagnostic criteria and therapeutic evaluation. j eur acad dermatol venereol. 2014;28(4):397 404. doi: 10.1111/jdv.12226. 10. grine rc, hendrix jd, greer ke. generalized eruptive keratoacanthoma of grzybowski: response to cyclophosphamide. j am acad dermatol. 1997; 36(5):786-787. doi: https://doi.org/10.1016/s0190-9622(97)80349-0. 11. pan a, reingold re, et. al. dermatological adverse events in prostate cancer patients treated with the androgen receptor inhibitor apalutamide. j urology. 2022; 207(5): 1010 1019. doi:10.1097/ju.0000000000002425. 12. sagawa n, watanabe, y, mizuno, y, takahashi s, and watanabe t. a case of toxic epidermal necrolysis associated with apalutamide administration. j cut immuno allergy. 2020; 3(6): 134-135. doi:10.1002/cia2.12138. w e e k 4 re sp o n se r a te ( % ) w e e k 4 re sp o n se r a te ( % ) 75 50 25 100 0 be sure 76.5* 31.4 bkz (n=319) ada (n=159) be vivid 76.9* 15.3 bkz (n=321) ust (n=163) be radiant 47.3 71.0* bkz (n=373) sec (n=370) be ready 75.9 bkz (n=349) 75 50 25 100 0 be sure 15.4† 1.3 bkz (n=319) ada (n=159) be vivid 15.0† 1.2 bkz (n=321) ust (n=163) be radiant 6.2 13.9† bkz (n=373) sec (n=370) be ready 18.9 bkz (n=349) 75 50 25 100 0 be sure 39.5† 5.0 bkz (n=319) ada (n=159) be vivid 43.6† 3.1 bkz (n=321) ust (n=163) be radiant 17.6 35.9† bkz (n=373) sec (n=370) be ready 45.3 bkz (n=349) 75 50 25 100 0 be sure 37.6‡ 25.8 bkz (n=319) ada (n=159) be vivid 37.4† 11.0 bkz (n=321) ust (n=163) be radiant 40.8 57.9† bkz (n=373) sec (n=370) be ready 43.0 bkz (n=349) w e e k 4 re sp o n se r a te ( % ) w e e k 4 re sp o n se r a te ( % ) summary presented at the 42nd annual fall clinical dermatology conference | las vegas, nv | october 20–23, 2022 objective to evaluate early clinical and health-related quality of life (hrqol) responses at week 4 in patients with moderate to severe plaque psoriasis treated with bimekizumab (bkz), adalimumab (ada), ustekinumab (ust), and secukinumab (sec) in four phase 3/3b trials. introduction • speed of response is an important treatment consideration for patients with plaque psoriasis;1 90% of patients in a recent cross-sectional survey ranked rapid response as high importance, with an average expectation of complete skin clearance within 4 weeks.2 • improvement in hrqol is also an important treatment goal, given that psoriasis is a chronic disease and can place a significant burden on patients’ lives.3,4 materials and methods • data are reported in parallel from be sure, be vivid, be radiant, and be ready for patients who received bkz 320 mg every 4 weeks (q4w) or active comparators (figure 1).5–8 • we report the proportion of patients achieving a ≥75% improvement from baseline in psoriasis area and severity index (pasi 75), pasi 90, pasi 100, and dermatology life quality index (dlqi) 0/1 at week 4 in each trial. • missing data were accounted for using non-responder imputation (nri). results • these analyses include 478 patients from be sure (319 bkz; 159 ada), 484 patients from be vivid (321 bkz; 163 ust), 743 patients from be radiant (373 bkz; 370 sec), and 349 patients from be ready (349 bkz); baseline characteristics of these patients have been reported previously.5–8 • at week 4, pasi 75, pasi 90, and pasi 100 were achieved by a greater proportion of bkz-randomized patients vs active comparators (figure 2). • furthermore, a greater proportion of patients randomized to bkz vs active comparators achieved dlqi 0/1 at week 4 (figure 2). conclusions at week 4, after one dose of bkz, greater levels of skin clearance and hrqol benefits were observed compared with two doses of ada, one dose of ust, and four doses of sec. results were consistent across the four phase 3/3b trials. a. blauvelt,1 k.c. duffin,2 n. magnolo,3 j. weisman,4 m. ståhle,5 d. wilsmann-theis,6 m. wang,7 k. wixted,7 b. szilagyi,8 l. puig9 bimekizumab speed of response in patients with moderate to severe plaque psoriasis: results from four phase 3/3b trials (be vivid, be ready, be sure, and be radiant) previously presented at spin 2022 institutions: 1oregon medical research center, portland, oregon, usa; 2department of dermatology, university of utah, salt lake city, utah, usa; 3department of dermatology, university hospital münster, münster, germany; 4medical dermatology specialists, inc., atlanta, georgia, usa; 5department of medicine, karolinska institutet, solna, sweden; 6university hospital bonn, university of bonn, bonn, germany; 7ucb pharma, raleigh, north carolina, usa; 8ucb pharma, monheim, germany; 9hospital de la santa creu i sant pau, universitat autònoma de barcelona, barcelona, spain. references: 1kornmehl h et al. dermatology 2021;237:151–157; 2gorelick j et al. dermatol ther (heidelb) 2019;9:785–797; 3takeshita j et al. j am acad dermatol 2017;76:377–390; 4blauvelt a et al. j drugs dermatol 2020;19:487–492; 5warren rb et al. n engl j med 2021;385:130–141, nct03412747; 6reich k et al. lancet 2021;397:487–498, nct03370133; 7reich k et al. n engl j med 2021;385:142–152, nct03536884; 8gordon kb et al. lancet 2021;397:475–486, nct03410992. author contributions: substantial contributions to study conception/design, or acquisition/analysis/interpretation of data: ab, kcd, nm, jw, ms, dwt, mw, kw, bs, lp; drafting of the publication, or revising it critically for important intellectual content: ab, kcd, nm, jw, ms, dwt, mw, kw, bs, lp; final approval of the publication: ab, kcd, nm, jw, ms, dwt, mw, kw, bs, lp. author disclosures: ab:has served as a speaker (received honoraria) for abbvie, arcutis, bristol myers squibb, eli lilly, pfizer, regeneron, sanofi, and ucb pharma, served as a scientific adviser (received honoraria) for abbvie, abcentra, affibody, aligos, almirall, alumis, amgen, anaptysbio, arcutis, arena, aslan, athenex, bluefin biomedicine, boehringer ingelheim, bristol myers squibb, cara therapeutics, dermavant, ecor1, eli lilly, escient, evelo, evommune, forte, galderma, highlightii pharma, incyte, innoventbio, janssen, landos, leo pharma, merck, novartis, pfizer, rapt, regeneron, sanofi genzyme, spherix global insights, sun pharma, tll pharmaceutical, trialspark, ucb pharma, vibliome, and xencor, and has acted as a clinical study investigator (institution has received clinical study funds) for abbvie, acelyrin, almirall, amgen, arcutis, athenex, boehringer ingelheim, bristol myers squibb, concert, dermavant, eli lilly , evelo, evommune, galderma, incyte, janssen, leo, merck, novartis, pfizer, regeneron, sun pharma, and ucb pharma. kcd: received grants/investigator for abbvie, amgen, bristol myers squibb, celgene, eli lilly, janssen, novartis, pfizer, regeneron, sienna, stiefel, and ucb pharma; speaker’s bureau for novartis (non-promotional only); consultant/advisory board for abbvie, amgen, bristol myers squibb, celgene, eli lilly, janssen, novartis, ortho dermatologics, pfizer, sienna, stiefel, and ucb pharma. nm: honoraria for participation on advisory boards, as a speaker and for consultancy from abbvie, almirall, bristol myers squibb, boehringer ingelheim, celgene, eli lilly, janssen, leo pharma, novartis, pfizer, and ucb pharma. jw: research grants from abbvie, amgen, avillion, boehringer ingelheim, bristol myers squibb, chemocentryx, dermira, gsk, inflarx, leo pharma, janssen, novartis, pfizer, regeneron, sanofi, and ucb pharma; consulting fees from abbvie, janssen, novartis, regeneron, sanofi, and ucb pharma; speaker’s bureau from abbvie, janssen, novartis, regeneron, and sanofi. ms: has received honoraria for participating in advisory boards and has given lectures for abbvie, celgene, eli lilly, leo pharma, lipidor, novartis, pfizer, and ucb pharma. dwt: has been an advisor and/or received speakers’ honoraria or travel expense reimbursements and/or received grants and/or participated in clinical trials of the companies abbvie, almirall, amgen, beiersdorf, biogen, boehringer ingelheim, celgene, forward pharma, gsk, janssen, leo pharma, eli lilly, medac, merck, novartis, pfizer, ucb pharma, and vbl. mw, kw, bs: employees and shareholders of ucb pharma. lp: received consultancy/speaker’s honoraria from and/or participated in trials sponsored by abbvie, almirall, amgen, baxalta, biogen, boehringer ingelheim, celgene, eli lilly, gebro, janssen, js biocad, leo pharma, merck-serono, msd, mylan, novartis, pfizer, regeneron, roche, samsung-bioepis, sandoz, sanofi genzyme, and ucb pharma. acknowledgements: this study was funded by ucb pharma. we thank the patients and their caregivers in addition to the investigators and their teams who contributed to this study. the authors acknowledge susanne wiegratz, msc, ucb pharma, monheim, germany, for publication coordination, natalie nunez gomez, md, ucb pharma, monheim, germany, for critical review, yasha najafi, msc, costello medical, london, uk, for medical writing and editorial assistance and the design team, costello medical, uk for graphic design assistance. all costs associated with development of this poster were funded by ucb pharma. figure 1 study design: included patients ada: adalimumab; bkz: bimekizumab; bsa: body surface area; dlqi: dermatology life quality index; hrqol: health-related quality of life; pasi 75/90/100: ≥75%/≥90%/100% improvement from baseline in psoriasis area and severity index; q2w: every 2 weeks; q4w: every 4 weeks; q12w: every 12 weeks; sec: secukinumab; ust: ustekinumab. pasi 75 figure 2 week 4 pasi 75, pasi 90, pasi 100, and dlqi 0/1 responses in be sure, be vivid, be radiant, and be ready (nri) p values for the comparison of treatment groups were based on the cochran-mantel-haenszel test from the general association. in be sure, be vivid, and be radiant, comparisons between bkz and active comparators at week 4 for pasi 90, pasi 100, and dlqi 0/1 were not pre-specified and therefore were not controlled for multiplicity; the corresponding p values are nominal for all trials. comparisons for pasi 75 response at week 4 were pre-specified and were controlled for multiplicity in all trials. *p<0.001 vs active comparator; †nominal p<0.001 vs active comparator; ‡nominal p=0.010 vs active comparator. be vivid and be ready included placebo arms which were not included in these analyses. aall patients randomized to bimekizumab received 320 mg q4w; ball patients randomized to adalimumab in be sure received 80 mg at baseline, 40 mg at week 1, then q2w; cpatients in be vivid received ustekinumab at baseline, week 4, then q12w. ustekinumab dosing was based on patient weight at baseline: patients weighing ≤100 kg received one ustekinumab 45 mg injection and one placebo injection, patients >100 kg received two ustekinumab 45 mg injections; dall patients randomized to secukinumab in be radiant received 300 mg weekly to week 4, then q4w. pasi 90 pasi 100 dlqi 0/1 be ready⁸ 0 4week be sure⁵ bimekizumab 320 mga (n=319) adalimumab 40 mgb (n=159) n=478 be radiant⁷be vivid⁶ 0 4week bimekizumab 320 mga (n=321) ustekinumab 45/90 mgc (n=163) n=484 0 4week bimekizumab 320 mga (n=373) secukinumab 300 mgd (n=370) n=743 0 4week bimekizumab 320 mga (n=349) n=349 dose schedule 80 mg dose data are reported in parallel from the initial 4-week treatment period of be sure, be vivid, be radiant, and be ready bimekizumab adalimumab ustekinumab secukinumab vs at week 4: greater skin clearance with bimekizumab; including higher rates of pasi 100 health-related quality of life benefit with bimekizumab; as measured by dlqi 0/1 présentation powerpoint c1 internal use funding : this study was funded by laboratoire dermatologique la roche-posay group d0 d7 d14 d28 d56 dc 5.35±2.44 5.48±2.56 4.87±2.90 2.96±1.85 1.96±1.30 dc combined with bpo 6.71±3.27 6.29±3.52 3.57±1.86 1.90±2.34 1.00±1.22 bpo 6.10±2.51 5.10±2.65 3.25±2.27 1.65±1.76 0.65±0.75 group d0 d7 d14 d28 d56 dc 11.65±3.27 11.57±3.01 9.43±3.58 5.61±2.92 3.57±2.59 dc combined with bpo 15.38±4.33 13.57±4.35 8.43±3.23 4.33±3.17 2.14±1.96 bpo 13.05±4.65 11.65±4.21 8.65±3.53 5.50±2.61 3.45±1.76 group d0 d7 d14 d28 d56 dc 6.30±3.55 6.09±3.19 4.57±2.84 2.65±1.85 1.61±2.06 dc combined with bpo 8.67±4.95 7.29±4.48 4.86±2.90 2.43±1.83 1.14±1.28 bpo 6.95±4.52 6.55±4.07 5.40±3.52 3.85±1.79 2.80±1.58 skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 252 resident competition research articles successful treatment of generalized pustular psoriasis of pregnancy with oral cyclosporine zahra najmi, md,1 ali sayyadinejad, md,2 narges mohammadi, md,3 shahla atrak, md,1 nader ghaffari, md,4 hamid khederlou, md5 1department of obstetrics and gynecology, zanjan university of medical sciences, zanjan, iran 2department of dermatology, zanjan university of medical sciences, zanjan, iran 3student research center, zanjan university of medical sciences, zanjan, iran 4md, anatomical and clinical pathologist, booali laboratory, zanjan, iran 5resident of cardiology, tehran heart center, tehran university of medical sciences, tehran, iran generalized pustular psoriasis of pregnancy (gppp) or impetigo herpetiformis is a rare and severe dermatosis which usually occurs during the third trimester of pregnancy.1,2 it presents with generalized erythematous plaques, peripheral scales and non-infectious pustules symmetrically and grouped and often starting in the flexures and intertriginous areas and then spreads to the entire body.2,3,4 many studies have suggested that pathogenesis is unknown.5 it can be associated with constitutional symptoms including fever, diarrhea, pain, gastrointestinal upset, malaise and arthralgia.2,6,7 various factors play a role in triggering gppp, such as topical therapy (coal tar, anthralin), pregnancy, infection, hypocalcemia, hypoparathyroidism and drugs.8 gppp usually disappears after delivery,9 however, if untreated during pregnancy there is an increase in the risk of stillbirth.10,11 complications include fluid and electrolyte imbalance such as hypocalcaemia and secondary infection, sepsis, intrauterine growth retardation, premature delivery and fetal abnormalities due to placental insufficiency.6,12,13 it is difficult to control the disease during pregnancy, especially when mother is unstable and there is no response to systemic steroids.9 we report a case of generalized pustular psoriasis of pregnancy, which was successfully treated with cyclosporine. a 26-year-old female, gravida 1, para 0, in 37 weeks of pregnancy, was referred to our tertiary center for a recently appearing and introduction case presentation generalized pustular psoriasis of pregnancy (gppp) is a rare dermatosis that usually occurs during the third trimester of pregnancy. the diagnosis is primarily clinical, confirmed by laboratory investigations and histopathological typical findings. here we report, a 26-year-old, gravida one woman, in 37 weeks of pregnancy, presenting with extensive erythematous, pruritic plaques with peripheral scaling and pustules. patient was induced at 37+4 weeks and delivered a healthy 2900g male infant. gppp was eventually controlled with oral cyclosporine. abstract https://www.ncbi.nlm.nih.gov/pubmed/?term=patsatsi%20a%5bauthor%5d&cauthor=true&cauthor_uid=23626548 skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 253 progressive generalized skin eruption. she had extensive erythematous, pruritic plaques with peripheral scaling and pustules. on initial physical examination, the abdomen and back showed characteristic pustular eruption with erythema suggestive of pustular psoriasis of pregnancy (figure 1a). the patient had no personal or family history of psoriasis and no relevant drug history. antenatal examinations were carried out at regular intervals, with no found signs of placental insufficiency. fetal movements and fetal heart rate were normal. initially the patient was put on topical steroids (triamcinolone) and told to use petrolatum. oral antibiotics were administered to avoid secondary bacterial infection. partial response was achieved in primary lesions after 3 days, but new pustular lesions appeared on the face, buttocks and limbs (figure 1b,c,d). at 37+ 4 weeks, the patient had electrolyte imbalance and a fever. because of the risk of stillbirth and perinatal mortality, labor was induced, and patient gave birth to a 2900g male infant with a normal vaginal delivery. she was transferred to icu. cyclosporine was added in order to prevent the development of new lesions and elimination of prior lesions. lab tests showed low levels of albumin, calcium and iron, thus albumin 20%, ca-d and ferofolic were also begun. culture both the fungal and bacterial cultures of the pustular lesions were negative. laboratory investigations blood analyses were carried out throughout the time of hospitalization. laboratory tests showed leukocytosis of 19.200/mm3 with a raised erythrocyte sedimentation rate (esr) and c reactive protein (crp). serum levels of calcium, albumin and iron were low. parathormone hormone, serum levels of sodium and potassium, rheumatologic tests, blood cultures and other laboratory investigations were within normal limits (or negative). figure 1. extensive erythematous, pruritic plaques with peripheral scaling and sterile pustules on the abdomen and back, suggestive of pustular psoriasis of pregnancy (a). pustular lesions on the face (b), buttocks (c) and limbs (d). histopathology the histopathological findings included focal parakeratosis, acanthosis, elongated rete ridges, and subcorneal and intraepidermal spongiform pustules of kogoj, containing neutrophils, munro microabscesses, as well as perivascular and papillary dermal infiltration of lymphocytes and neutrophils. pathological diagnosis was pustular psoriasis of pregnancy (figure 2). outcome and follow-up improvement of pustular psoriasis lesions began after 8 days treatment with cyclosporine. the patient presented with only residual hyperpigmentation and desquamation 17 days later (figure 3). after resolution of cutaneous symptoms and hemodynamic stability, she was discharged from the hospital. skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 254 figure 2. (a) subcorneal and intraepidermal spongiform pustules of kogoj (he; ×200). (b) papillary dermal infiltration of lymphocytes and neutrophils (he; ×400). figure 3. healed lesions of pustular psoriasis with only residual hyperpigmentation and desquamation. we report a case of generalized pustular psoriasis of pregnancy (gppp) or impetigo herpetiformis with low levels of calcium, albumin and iron, raised esr and crp and leukocytosis, treated with topical corticosteroid and oral cyclosporine. psoriasis is a chronic disease with a mean prevalence of 2% worldwide. clinical types have been classified: guttate, nail, inverted, vulgaris, keratodermic, pustular and erythrodermic. pustular psoriasis can be localized or widespread, similar to our case in this study.10,11 gppp is characterized by macroscopic pustules and is the most difficult variant of generalized pustular psoriasis to treat. 200 cases of gppp have been reported up to now and it is still a matter of discussion regarding causes and treatment.2,3,9 etiology is still unknown. although it may be related to hypocalcemia, hypoparathyroidism, reduced epidermal antileukoproteinase activity and high progesterone in the third trimester of pregnancy. however, these findings can only be seen in a small number of patients.9,10,14 prior studies have reported personal and family history of psoriasis in patients with gppp.10,11 the diagnosis of gppp primarily clinical with support from laboratory investigations and histopathological typical findings. clinical examination is characterized by generalized erythematous plaques with peripheral scales and sterile pustules symmetrically and grouped and often starting in the flexures and intertriginous areas. other signs and symptoms include poor general condition, fever, diarrhea, dehydration, tachycardia and seizures. laboratory findings that may be detected are leukocytosis, raised esr and crp, and negative bacterial and fungal cultures of pustules. low calcium, phosphate and albumin and low parathyroid hormone levels are also common laboratory findings. histopathological findings that confirm the diagnosis include parakeratosis, epidermal acanthosis and papillomatosis, elongated reteridges, neutrophilic inflammatory collections, intraepidermal microabscesses (spongiform pustules of kogoj) and papillary discussion skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 255 dermal infiltration of lymphocytes.4,6,9,10,11 early treatment of gppp improves the prognosis for both the mother and fetus. the choice of treatment during pregnancy is systemic corticosteroids, with prednisone 3060 mg/day. postpartum treatment is with cyclosporine.2,6,15,16 topical steroids are used to reduce cutaneous manifestations.2,17,18 even if the pustules are non-infectious, antibiotics have been suggested to avoid secondary bacterial infection.6,10,11 supportive treatment includes fluid and electrolyte balance, pain management and intensive care and fetal monitoring in case of emergency early delivery.5,19 in our case, topical steroids were initially begun along with antibiotic treatment. because of the severity of the disease and risk to the fetus, labor was induced, and cyclosporine was added. conflict of interest disclosures: none funding: none corresponding author: dr narges mohammadi student research center zanjan university of medical sciences zanjan, iran e-mail: dr.nargesmohammadi@yahoo.com references: 1. luan l, han s, zhang z, liu x. personal treatment experience for severe generalized pustular psoriasis of pregnancy: two case reports. dermatol ther. 2014 may-jun;27(3):1747. 2. shah a, makhecha m. pustular psoriasis of pregnancy with acrodermatitis continua of hallopeau. indian j dermatol. 2016;61(1):123. 3. hazarika d. generalized pustular psoriasis of pregnancy successfully treated with cyclosporine. indian j dermatol venereol leprol. 2009;75(6):638. 4. oumeish oy, farraj se, bataineh as. some aspects of impetigo herpetiformis. arch dermatol 1982;118:103-5. 5. nasser n, sasseville d. dermatologic diseases of pregnancy. dermatologie conferences scientifiques. 2006;5:1–6. 6. shaw cj, wu p, sriemevan a. first trimester impetigo herpetiformis in multiparous female successfully treated with oral cyclosporine. bmj case rep. 2011;12:11-20. 7. champion rh, burton jl, burns da. rook’s textbook of dermatology. sixth edition oxford: blackwell scientific publications. 1998;16:39-40. 8. keerthi s, rangaraj m, karthikeyan k. telmisartan aggravates pustular psoriasis. j pharmacol pharmacother. 2015;6(2):107-9. 9. patsatsi a, theodoridis td, vavilis d, tzevelekis v, kyriakou a, kalabalikis d, et al. cyclosporine in the management of impetigo herpetiformis: a case report and review of the literature. case rep dermatol. 2013;5(1):99-104. 10. kondo rn, araújo fm, pereira am, lopes vc, martins lm. pustular psoriasis of pregnancy (impetigo herpetiformis)-case report. an bras dermatol. 2013;88(6):186-9. 11. azulay-abulafia l, brotas a, braga a, volta ac, gripp ac. psoríase pustulosa da gestação (impetigo herpetiforme): relato de dois casos e revisão na literatura. rev bras ginecol obstet. 2004;26:153–159. 12. vun yy, jones b, al-mudhaffer m, egan c. generalized pustular psoriasis of pregnancy treated with narrowband uvb and topical steroids. j am acad dermatol. 2006;54(2):28–30. 13. bin yap fb. impetigo herpetiformis: a rare dermatosis of pregnancy. south med j. 2009;102:1186–7. 14. roth mm. pregnancy dermatoses: diagnosis, management, and controversies. am j clin dermatol. 2001;12:25–41 15. brightman l, stefanato cm, bhawan j, phillips tj. third-trimester impetigo herpetiformis treated with cyclosporine. j am acad dermatol. 2007;56(2): 62–4 16. martins ga, arruda l. systemic treatment of psoriasis part i: methotrexate and acitretin. an bras dermatol. 2004;79:263–278. 17. okuno h, ogura k, okuyama r, itoi e. two cases of acrodermatitis continua of hallopeau associated with generalized arthritis. acta dermatovenerol croat. 2013;21:265–7 18. imai n, watanabe r, fujiwara h, ito m, nakamura a. successful treatment of impetigo herpetiformis with oral cyclosporine during pregnancy. arch dermatol. 2002;138(1):128–9. 19. arslanpence i, dede fs, gokcu m, gelisen o. impetigo herpetiformis unresponsive to therapy in a pregnant adolescent. j pediatr adolesc gynecol. 2003;16(3):129–132. mailto:dr.nargesmohammadi@yahoo.com https://www.ncbi.nlm.nih.gov/pubmed/?term=luan%20l%5bauthor%5d&cauthor=true&cauthor_uid=24517287 https://www.ncbi.nlm.nih.gov/pubmed/?term=han%20s%5bauthor%5d&cauthor=true&cauthor_uid=24517287 https://www.ncbi.nlm.nih.gov/pubmed/?term=zhang%20z%5bauthor%5d&cauthor=true&cauthor_uid=24517287 https://www.ncbi.nlm.nih.gov/pubmed/?term=liu%20x%5bauthor%5d&cauthor=true&cauthor_uid=24517287 file:///d:/pustular%20psoriasis/generalized%20pustular%20psoriasis%20of%20pregnancy%206.htm https://www.ncbi.nlm.nih.gov/pubmed/?term=shah%20a%5bauthor%5d&cauthor=true&cauthor_uid=26955145 https://www.ncbi.nlm.nih.gov/pubmed/?term=makhecha%20m%5bauthor%5d&cauthor=true&cauthor_uid=26955145 https://www.ncbi.nlm.nih.gov/pubmed/26955145 https://www.ncbi.nlm.nih.gov/pubmed/?term=hazarika%20d%5bauthor%5d&cauthor=true&cauthor_uid=19915261 https://www.ncbi.nlm.nih.gov/pubmed/?term=generalized+pustular+psoriasis+of+pregnancy+successfully+treated+with+cyclosporine https://www.ncbi.nlm.nih.gov/pubmed/?term=shaw%20cj%5bauthor%5d&cauthor=true&cauthor_uid=22696729 https://www.ncbi.nlm.nih.gov/pubmed/?term=wu%20p%5bauthor%5d&cauthor=true&cauthor_uid=22696729 https://www.ncbi.nlm.nih.gov/pubmed/?term=sriemevan%20a%5bauthor%5d&cauthor=true&cauthor_uid=22696729 https://www.ncbi.nlm.nih.gov/pubmed/?term=first+trimester+impetigo+herpetiformis+in+multiparous+female+successfully+treated+with+oral+cyclosporine https://www.ncbi.nlm.nih.gov/pubmed/?term=first+trimester+impetigo+herpetiformis+in+multiparous+female+successfully+treated+with+oral+cyclosporine https://www.ncbi.nlm.nih.gov/pubmed/?term=keerthi%20s%5bauthor%5d&cauthor=true&cauthor_uid=25969662 https://www.ncbi.nlm.nih.gov/pubmed/?term=rangaraj%20m%5bauthor%5d&cauthor=true&cauthor_uid=25969662 https://www.ncbi.nlm.nih.gov/pubmed/?term=karthikeyan%20k%5bauthor%5d&cauthor=true&cauthor_uid=25969662 https://www.ncbi.nlm.nih.gov/pubmed/?term=telmisartan+aggravates+pustular+psoriasis https://www.ncbi.nlm.nih.gov/pubmed/?term=telmisartan+aggravates+pustular+psoriasis https://www.ncbi.nlm.nih.gov/pubmed/?term=patsatsi%20a%5bauthor%5d&cauthor=true&cauthor_uid=23626548 https://www.ncbi.nlm.nih.gov/pubmed/?term=theodoridis%20td%5bauthor%5d&cauthor=true&cauthor_uid=23626548 https://www.ncbi.nlm.nih.gov/pubmed/?term=vavilis%20d%5bauthor%5d&cauthor=true&cauthor_uid=23626548 https://www.ncbi.nlm.nih.gov/pubmed/?term=tzevelekis%20v%5bauthor%5d&cauthor=true&cauthor_uid=23626548 https://www.ncbi.nlm.nih.gov/pubmed/?term=tzevelekis%20v%5bauthor%5d&cauthor=true&cauthor_uid=23626548 https://www.ncbi.nlm.nih.gov/pubmed/?term=kyriakou%20a%5bauthor%5d&cauthor=true&cauthor_uid=23626548 https://www.ncbi.nlm.nih.gov/pubmed/?term=kalabalikis%20d%5bauthor%5d&cauthor=true&cauthor_uid=23626548 https://www.ncbi.nlm.nih.gov/pubmed/?term=sotiriadis%20d%5bauthor%5d&cauthor=true&cauthor_uid=23626548 https://www.ncbi.nlm.nih.gov/pubmed/?term=pustular+psoriasis+of+pregnancy+%28impetigo+herpetiformis%29+-+case+report*+cyclosporine+in+the+management+of+impetigo+herpetiformis%3a+a+case+report+and+review+of+the+literature https://www.ncbi.nlm.nih.gov/pubmed/?term=pustular+psoriasis+of+pregnancy+%28impetigo+herpetiformis%29+-+case+report*+cyclosporine+in+the+management+of+impetigo+herpetiformis%3a+a+case+report+and+review+of+the+literature https://www.ncbi.nlm.nih.gov/pubmed/?term=kondo%20rn%5bauthor%5d&cauthor=true&cauthor_uid=24346915 https://www.ncbi.nlm.nih.gov/pubmed/?term=ara%c3%bajo%20fm%5bauthor%5d&cauthor=true&cauthor_uid=24346915 https://www.ncbi.nlm.nih.gov/pubmed/?term=pereira%20am%5bauthor%5d&cauthor=true&cauthor_uid=24346915 https://www.ncbi.nlm.nih.gov/pubmed/?term=lopes%20vc%5bauthor%5d&cauthor=true&cauthor_uid=24346915 https://www.ncbi.nlm.nih.gov/pubmed/?term=martins%20lm%5bauthor%5d&cauthor=true&cauthor_uid=24346915 https://www.ncbi.nlm.nih.gov/pubmed/24346915 https://www.ncbi.nlm.nih.gov/pubmed/24346915 https://www.ncbi.nlm.nih.gov/pubmed/?term=imai%20n%5bauthor%5d&cauthor=true&cauthor_uid=11790187 https://www.ncbi.nlm.nih.gov/pubmed/?term=watanabe%20r%5bauthor%5d&cauthor=true&cauthor_uid=11790187 https://www.ncbi.nlm.nih.gov/pubmed/?term=fujiwara%20h%5bauthor%5d&cauthor=true&cauthor_uid=11790187 https://www.ncbi.nlm.nih.gov/pubmed/?term=ito%20m%5bauthor%5d&cauthor=true&cauthor_uid=11790187 https://www.ncbi.nlm.nih.gov/pubmed/?term=nakamura%20a%5bauthor%5d&cauthor=true&cauthor_uid=11790187 skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 464 original research the integrated 31-gene expression profile test (i31-gep) for cutaneous melanoma outperforms the cp-gep at identifying patients who can forego sentinel lymph node biopsy when applying nccn guidelines alex m. glazer, md1, michael tassavor, md2, dustin portela do3, teo soleymani, md4 1 glazer dermatology, dermatology science and research foundation, buffalo grove, il 2 skin cancer center, cincinnati, oh 3 treasure valley dermatology, boise, id 4 mohs micrographic and dermatologic surgery, cutaneous oncology, division of dermatology, david geffen school of medicine, university of california, los angeles, ca abstract introduction: eighty-eight percent of patients who receive a sentinel lymph node biopsy (slnb) receive a negative result. current guidelines suggest avoiding slnb if the risk of positivity is <5%. a low threshold for performing slnb indicates worry about missing positive nodes but results in many unnecessary biopsies. the integrated 31-gene expression profile (i31-gep) test combines the 31-gep with breslow thickness, age, ulceration, and mitotic rate using a validated neural network algorithm to identify patients with <5% risk by reporting a precise, individualized likelihood score. using logistic regression, a separate gep (8 genes plus breslow thickness and age; cp-gep) also aims to identify patients who can forego slnb by binning patients into lowand high-risk categories. this study compared the i31gep for slnb with the cp-gep to identify patients who can safely forego slnb. methods: this study evaluated the genes, gene pathways, and relative contribution of the two gene signatures relative to clinical and pathologic factors and further analyzed patients with t1b-t2 tumors from previously published studies in u.s. cohorts for the i31-gep (n=763) and cp-gep (n=153). a ratio of true-to-false-negative i31-gep for slnb and cpgep test results was compared to the guideline-established ratio of 19 negatives to one missed positive (19:1) if foregoing slnb using a 5% risk threshold. results: the i31-gep had a 30:1 true-to-false-negative ratio, compared to 15:1 using cpgep. in t1b tumors, the i31-gep ratio increased to 35:1 compared to 14:1 using cp-gep. limitations: retrospective design, which could lead to bias. patients included in both analyses were primarily from institutional surgical centers, and referral bias may not make the result generalizable. conclusion: only the i31-gep provided benefit over guideline-established care for identifying patients with low risk of sln positivity. skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 465 the multicenter selective lymphadenectomy trial (mslt-1) demonstrated that the sentinel lymph node biopsy (slnb) is a prognostic indicator of survival outcomes.1 patients with a positive slnb (~21%) had worse 5-year melanoma-specific survival (mss) than those with a negative node. however, the sensitivity of a positive node identifying patients likely to die from melanoma was 39%, the positive predictive value was 34%, and the negative predictive value was 90%. moreover, a recent study showed that patients with t1b/t2a tumors with a positive slnb had survival equal to stage iiia, with an associated 94% 5-year mss.2 although recent discussion highlights that slnb may have therapeutic benefits in slnb-positive patients to control disease recurrence in the nodal basin,3 these results highlight two important facts: 1) many patients may not need an slnb and still have high survival rates and 2) recurrence or death prognostication in patients with a negative slnb is critical to identify patients at high risk despite being sln negative. gene expression profile (gep) tests have shown value in other cancer types to improve patient care. oncotype is a 21-gep used to identify patients at high and low risk of recurrence, and the 15-gep test for uveal melanoma has become the standard of care to identify patients at the highest risk of poor outcomes.4,5 similarly, two gep tests for cutaneous melanoma have been developed to aid clinicians in risk-aligned patient care decisions. the 31-gep (decisiondx-melanoma; castle biosciences, inc., friendswood, tx) is a gene expression profile test launched in 2013 that provides patients with their precise risk of having a positive sln and their individual risk of recurrence, metastasis, and death from melanoma. the test analyzes the expression of 31-gene targets and has been validated as a statistically significant predictor of recurrence, distant metastasis, and death, independent of other clinical and pathological features.6–11 the 31-gep continuous risk score has been integrated with clinical and pathological features (breslow thickness, mitotic rate, ulceration, and age) using a neural network algorithm to determine a precise risk score for sln positivity (i31-gep slnb) and the 31-gep score was a significant and independent contributor.12 the i31-gep algorithm for slnb was shown to provide benefit for selecting patients for slnb over treating all with slnb.13 this test also provides each patient with their personalized risk of sln metastasis rather than binning patients as high or low risk, which may miss the nuances associated with each patient’s specific tumor, and, ultimately, preclude opportunities for shared decision-making between the patient and clinician. the cp-gep test (clinicopathologic + gep; merlin; skylinedx, rotterdam, the netherlands) has recently become clinically available. it provides a patient with a risk of a positive slnb being high or low. this test combines an 8 gene analysis with breslow thickness and age to identify patients at low risk of sln metastasis. of note, the cp-gep test’s ability to predict the risk of recurrence, metastasis, or death from melanoma is undergoing development and is not clinically available.14,15 in addition, based upon a review of published literature, the 8-gep alone has never been demonstrate to provide independent information to the ajcc clinical and pathologic factors (breslow’s thickness and age) included in the cp-gep test through multivariable analysis. introduction skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 466 the purpose of this study was to compare the i31-gep for slnb to the cp-gep using two published u.s. cohorts to identify which test better identified patients who can safely forego slnb when applying nccn guidelines. patients with t1b-t2 tumors tested with the i31-gep for slnb (n=763) from a multiinstitutional u.s. validation cohort10 were compared to patients tested with the cp-gep in a multi-institutional u.s. validation cohort (n=153).12,15 table 1 and table 2 compare the genes included in the two tests and the independent contributions of each gep to overall test performance. the 31-gep test analyzes the expression of 28 gene targets and three control genes using rt-pcr. the gene data is analyzed using radial basis machine learning and returns a continuous score between 0 and 1.0, with an increasing score associated with an increased risk of recurrence, metastasis, death, and sln positivity.11,12,16,17 the risk score obtained from the 31-gep test is integrated with breslow thickness, ulceration, mitotic rate, and age using a neural network derived algorithm to provide a precise risk of sln positivity (i31-gep for slnb).12, 13 the cp-gep test analyzes the expression of 8 genes and two control genes.14,19 individual gene data is combined with age and breslow thickness using logistic regression to provide a risk of sln positivity providing a binary highor low-risk classification.14,19 the slnb risk threshold is where the patient or clinician considers a balance between the harms of doing an invasive node biopsy versus the harms of missing a positive node. current nccn guidelines recommend not offering (i.e., avoiding) an slnb if the likelihood of a positive sln is <5%, although in our current era of shared decision-making, clinicians and their patients may use a higher or lower threshold.20 at a 5% threshold, clinicians are willing to perform 19 negative slnbs to find one positive node (19:1 negative-to-positive ratio).21–23 therefore, this analysis considers if the i31-gep for slnb or the cp-gep can perform better (having a higher ratio) than the 19:1 ratio used as the current nccn standard to forego slnb in patients with t1b-t2 tumors. at a 5% risk threshold for patients with t1bt2 tumors, the i31-gep for slnb identified 30 patients with true negative slns for every one positive sln missed (30:1 true-to-falsenegative ratio [154/5]). in contrast, using the cp-geps high/low-risk classification identified 15 patients with true negatives for every positive sln missed (15:1 true-tofalse-negative ratio [60/4]) (table 3). in patients with t1b tumors, for whom slnb guidance is likely to have the greatest impact, the i31-gep for slnb had a true-to-falsenegative ratio of 35:1 (105/3) (table 3) versus the cp-gep true-to-false-negative ratio of 14:1 (42/3) (table 3). slnb is primarily used as a prognostic staging procedure.24 most slnbs (88%) are negative, particularly in thin tumors.25,26 moreover, recent evidence suggests that 99% of patients with a t1b or t2a tumor with a positive sln are considered stage iiia and have 5-year untreated survival rates of 94%.2,27 therefore, identifying patients with a low likelihood of sln positivity who can safely forego slnb and have high survival methods results discussion skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 467 table 1. genes and associated pathways for i31-gep and 8-gep 31-gep ‡ 8-gep † genes pathways genes pathways cxcl14, clca2, s100a8, spp1, s100a9, bap1 migration, chemotaxis, metastasis mlana melanosome biogenesis cxcl14, mgp, spp1 chemokine/secreted molecules cxcl8, loxl4, tgfbr1 endothelial-mesenchymal transition, angiogenesis gja1, dsc1, ppl gap junction/cellular adhesion plat, serpin e2 endothelial-mesenchymal transition, blood coagulation crabp2, sprrib, btg1 differentiation, proliferation itgb3 endothelial-mesenchymal transition, cell adhesion, cell migration, blood coagulation lta4h lymphatic invasion gdf15 endothelial-mesenchymal transition, angiogenesis, metabolism, cachexia trim29 transcription factor tacstd2, clca2, robo1 cell surface receptors mgp, spp1, cst6 structural proteins krt6b, krt14 extracellular functions cxcl14 angiogenesis sap130, eif1b, aqp1, id2, arg2, rmb23, tyrp1 other ‡ gerami et al. 2015. † arias-mejias et al. 2020 skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 468 table 2. relative value of gene signatures compared to clinical and pathologic factors alone for i31-gep and cp-gep table 3. ratio of true to false negatives using the i31-gep or cp-gep in patients with t1b-t2 tumors i31-gep slnb algorithm † cp-gep algorithm variable variable importance assessment function ‡ loglikelihood value (g 2 ) variable auc p-value (vs. cp+gep) 31-gep score 100 91.3 p<.001 8-gep 0.78 not reported breslow thickness 56 53.5 p<.001 cp alone (breslow thickness, age) 0.78 not reported mitotic rate 25 20.7 p<.001 cp + gep 0.82 ulceration 83 19.1 p<.001 age 0 10.5 p=.001 † additional variables considered that were too sparse or did not improve algorithm fit: regression, sex, tumorinfiltrating lymphocytes, microsatellites, lymphovascular invasion, transected base, tumor location, and histologic subtype. ‡ variable importance sets the most important variable to 100 and the least important variable to 0. however, a value of 0 does not indicate a lack of contribution to the model. auc: area under the receiver operating characteristic curve. slnb: sentinel lymph node biopsy. cp: clinicopathologic feature. t1b-t2 tn fn ratio (true: false negative) i31-gep (n=763) 154 5 30:1 (154/5) nccn 5% risk† 19:1 cp-gep (n=153) 60 4 15:1 (60/4) t1b only tn fn ratio (true: false negative) i31-gep (n=279) 105 3 35:1 (105/3) nccn 5% risk† 19:1 cp-gep (n=74) 42 3 14:1 (42/3) †the nccn established risk threshold set at 5%, indicating that for every 20 similar patients undergoing slnb, 19 would receive a negative result for every one positive (19:1). skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 469 rates has the potential to reduce unnecessary slnbs, surgery-associated complications, and healthcare costs. each of the 2 gep tests analyzed used different genes and statistical methods during development16,28, similar to gep tests in breast cancer, including the 21-gep assay (oncotype dx breast) and the 50-gene assay (prosigna).4,29,30 therefore, understanding each tool’s development and validation process is important when assessing the utility of the tests. the 31-gep test was developed and validated through gene expression analysis using rt-pcr and radial basis machine learning to provide a risk score from 0-1.0 with reproducible test results during analytic validation,16,31 has been validated in multiple retrospective and prospective studies, and has been shown to influence treatment decisions in 50% of cases.6–8,10,17,32,33 the 31-gep has been integrated with clinical and pathological factors using a neural network algorithm to provide an individualized, precise risk of sln positivity (i31-gep).12 of the variables included in the i31-gep neural network, the 31-gep risk score was the most significant contributor to the model.12 the cp-gep model was developed using lasso (logistic regression and least absolute shrinkage and selection operator), combining an 8-gep gene signature with age and breslow thickness, with three retrospective validation studies.14,15,19,34 however, the gep portion of the cp-gep model has not shown independent prognostic information from breslow thickness and age (cp) using multivariable analysis,14,35 and bartlett et al. called into question the utility of the cp-gep compared to cp alone to guide slnb.35 this study found that the 31-gep performed better than current standards to identify patients with <5% risk of sln positivity while the cp-gep did not demonstrate an improvement over the 5% baseline standard. integrating the i31-gep could remove 30 patients (with t1b-t2 tumors) with a negative node for every one missed positive compared to 15 using cp-gep. the current study’s primary limitation is the retrospective design, which could lead to bias. in addition, the patients included in both the i31-gep and the cp-gep analyses are primarily from institutional surgical centers, and referral bias may not make the result generalizable. another limitation is that for the cp-gep test, only the validation study with a u.s. cohort was analyzed to minimize the potential impact of differences in slnb procedures between u.s. and european practice patterns. however, two european studies have analyzed the cp-gep test’s ability to identify low-risk patients. mulder et al. report on 105 patients with t1-t2 tumors, while johansson et al. report on 240 patients with t1-t2 tumors.19,34 combining these three studies showed that the cp-gep identified 177 true negatives and ten false negatives in patients with t1-t2 tumors for a ratio of 17:1 true-to-false-negatives (data not shown), suggesting that across all studies in t1-t2 patients, the cp-gep may not add benefit over current standards.19,34 in summary, we demonstrated that the i31gep for slnb has the potential to improve melanoma patient management by providing more accurate and actionable results for slnb guidance beyond the 5% standard to aid in risk-aligned and individualized patient care decisions, while the study findings suggest that the cp-gep may not. future studies may be helpful in further elucidating conclusion skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 470 the impact of the differences noted with this study. conflict of interest disclosures: none funding: materials and funding for this study were provided by castle biosciences, inc. (cbi) corresponding author: alex m glazer, md glazer dermatology dermatology science and research foundation buffalo grove, il email: alexglazer@gmail.com references: 1. morton, d. l. et al. final trial report of sentinel-node biopsy versus nodal observation in melanoma. the new england journal of medicine 370, 599–609 (2014). 2. moncrieff, m. d. et al. evaluation of the indications for sentinel node biopsy in earlystage melanoma with the advent of adjuvant systemic therapy: an international, multicenter study. ann surg oncol (2022) doi:10.1245/s10434-022-11761-4. 3. multicenter selective lymphadenectomy trials study group et al. therapeutic value of sentinel lymph node biopsy in patients with melanoma: a randomized clinical trial. jama surg (2022) doi:10.1001/jamasurg.2022.2055. 4. paik, s. et al. a multigene assay to predict recurrence of tamoxifen-treated, nodenegative breast cancer. the new england journal of medicine 351, 2817–26 (2004). 5. aaberg, t. m. et al. gene expression profiling in uveal melanoma: five-year prospective outcomes and meta-analysis. ocul oncol pathol 1–8 (2020) doi:10.1159/000508382. 6. hsueh, e. c. et al. long-term outcomes in a multicenter, prospective cohort evaluating the prognostic 31-gene expression profile for cutaneous melanoma. jco precision oncology 5, 589–601 (2021). 7. jarell, a. et al. the 31-gene expression profile stratifies recurrence and metastasis risk in patients with cutaneous melanoma. future oncology fon-2021-0996 (2021) doi:10.2217/fon-2021-0996. 8. arnot, s. p. et al. utility of a 31-gene expression profile for predicting outcomes in patients with primary cutaneous melanoma referred for sentinel node biopsy. am j surg 221, 1195–1199 (2021). 9. gastman, b. r. et al. identification of patients at risk of metastasis using a prognostic 31gene expression profile in subpopulations of melanoma patients with favorable outcomes by standard criteria. j am acad dermatol 80, 149-157.e4 (2019). 10. keller, j. et al. prospective validation of the prognostic 31‐gene expression profiling test in primary cutaneous melanoma. cancer med 8, 2205–2212 (2019). 11. zager, j. s. et al. performance of a prognostic 31-gene expression profile in an independent cohort of 523 cutaneous melanoma patients. bmc cancer 18, 130 (2018). 12. whitman, e. d. et al. integrating 31-gene expression profiling with clinicopathologic features to optimize cutaneous melanoma sentinel lymph node metastasis prediction. jco precision oncology 1466–1479 (2021) doi:10.1200/po.21.00162. 13. marchetti, m. a., dusza, s. w. & bartlett, e. k. utility of a model for predicting the risk of sentinel lymph node metastasis in patients with cutaneous melanoma. jama dermatology (2022) doi:10.1001/jamadermatol.2022.0970. 14. bellomo, d. et al. model combining tumor molecular and clinicopathologic risk factors predicts sentinel lymph node metastasis in primary cutaneous melanoma. jco precision oncology 319–334 (2020) doi:10.1200/po.19.00206. 15. yousaf, a. et al. validation of cp-gep (merlin assay) for predicting sentinel lymph node metastasis in primary cutaneous melanoma patients: a u.s. cohort study. international journal of dermatology n/a, (2021). 16. gerami, p. et al. development of a prognostic genetic signature to predict the metastatic risk associated with cutaneous melanoma. clin. cancer res. 21, 175–183 (2015). 17. vetto, j. t. et al. guidance of sentinel lymph node biopsy decisions in patients with t1–t2 melanoma using gene expression profiling. future oncology 15, 1207–1217 (2019). 18. jarell, a. et al. optimizing treatment approaches for patients with cutaneous melanoma by integrating clinical and pathologic features with the 31-gene expression profile test. journal of the american academy of dermatology mailto:alexglazer@gmail.com mailto:alexglazer@gmail.com skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 471 s0190962222022538 (2022) doi:10.1016/j.jaad.2022.06.1202. 19. mulder, e. e. a. p. et al. validation of a clinicopathological and gene expression profile model for sentinel lymph node metastasis in primary cutaneous melanoma. br j dermatol bjd.19499 (2020) doi:10.1111/bjd.19499. 20. nccn melanoma panel. nccn clinical practice guidelines in oncology (nccn guidelines): melanoma: cutaneous. at (2022). 21. vickers, a. j., van calster, b. & steyerberg, e. w. a simple, step-by-step guide to interpreting decision curve analysis. diagn progn res 3, 18 (2019). 22. vickers, a. j., van calster, b. & steyerberg, e. w. net benefit approaches to the evaluation of prediction models, molecular markers, and diagnostic tests. bmj i6 (2016) doi:10.1136/bmj.i6. 23. vickers, a. j., cronin, a. m., elkin, e. b. & gonen, m. extensions to decision curve analysis, a novel method for evaluating diagnostic tests, prediction models and molecular markers. bmc med inform decis mak 8, 53 (2008). 24. luke, j. j. et al. pembrolizumab versus placebo as adjuvant therapy in completely resected stage iib or iic melanoma (keynote-716): a randomised, doubleblind, phase 3 trial. the lancet 399, 1718– 1729 (2022). 25. chen, j. et al. prognostic role of sentinel lymph node biopsy for patients with cutaneous melanoma: a retrospective study of surveillance, epidemiology, and end-result population-based data. oncotarget 7, 45671– 45677 (2016). 26. egger, m. e. et al. should sentinel lymph node biopsy be performed for all t1b melanomas in the new 8th edition american joint committee on cancer staging system? journal of the american college of surgeons 228, 466–472 (2019). 27. gershenwald, j. e. et al. melanoma staging: evidence-based changes in the american joint committee on cancer eighth edition cancer staging manual. ca: a cancer journal for clinicians 67, 472–492 (2017). 28. arias-mejias, s. m. et al. primary cutaneous melanoma risk stratification using a clinicopathologic and gene expression model: a pilot study. international journal of dermatology 59, e431–e433 (2020). 29. sestak, i. et al. comparison of the performance of 6 prognostic signatures for estrogen receptor–positive breast cancer: a secondary analysis of a randomized clinical trial. jama oncol 4, 545 (2018). 30. wallden, b. et al. development and verification of the pam50-based prosigna breast cancer gene signature assay. bmc medical genomics 8, 54 (2015). 31. cook, r. w. et al. analytic validity of decisiondx-melanoma, a gene expression profile test for determining metastatic risk in melanoma patients. diagn pathol 13, 13 (2018). 32. dillon, l. d. et al. expanded evidence that the 31-gene expression profile test provides clinical utility for melanoma management in a multicenter study. curr med res opin 1–21 (2022) doi:10.1080/03007995.2022.2033560. 33. berger, a. c. et al. clinical impact of a 31gene expression profile test for cutaneous melanoma in 156 prospectively and consecutively tested patients. curr med res opin 32, 1599–1604 (2016). 34. johansson, i. et al. validation of a clinicopathological and gene expression profile model to identify patients with cutaneous melanoma where sentinel lymph node biopsy is unnecessary. european journal of surgical oncology s0748798321008143 (2021) doi:10.1016/j.ejso.2021.11.010. 35. bartlett, e. k., marchetti, m. a. & coit, d. g. gene expression profile-based risk modeling to select patients with melanoma who can avoid sentinel lymph node biopsy: are we there yet? jco precision oncology 988–989 (2020) doi:10.1200/po.20.00146. country of enrollment, n (%) us 514 (75.3) 262 (76.6) canada 169 (24.7) 80 (23.4) pga, n (%) 2 – mild 67 (9.8) 36 (10.5) 3 – moderate 559 (81.8) 277 (81.0) 4 – severe 57 (8.3) 29 (8.5) bsa affected, n (%) <10% 505 (73.9) 257 (75.1) ≥10% 178 (26.1) 85 (24.9) duration of disease, n (%) <5 years 154 (22.5) 73 (21.3) 5–10 years 128 (18.7) 89 (26.0) >10 years 401 (58.7) 180 (52.6) *includes patients with multiple races reported. itt population. bsa, body surface area; itt, intention-to-treat; pga, physician global assessment; qd, once daily. pga response by baseline disease characteristics and demographics ■ the primary endpoint (pga of 0 or 1 and ≥2-grade improvement at week 12) was met; pga response rates were highly statistically significant in the tapinarof cream 1% qd group versus the vehicle group in both psoaring 1 and 2: 35.4% vs 6.0% (p<0.0001) and 40.2% vs 6.3% (p<0.0001), respectively1 ■ the efficacy of tapinarof cream was consistent across subgroups, regardless of baseline disease characteristics such as pga score, %bsa affected, and duration of disease, and demographics such as sex, age, race, country of enrollment (figure 2) ■ notably, based upon the definition of pga response requiring achievement of pga=0 or 1 with ≥2-grade improvement, mild patients had to achieve complete disease clearance (pga=0) and severe patients had to improve a minimum of 3 points, to be responders figure 2. pga response at week 12 by baseline disease characteristics (a) and demographics (b) (pooled psoaring 1 and 2) *lower limit of the 95% ci for the relative risk >1, indicating a significantly higher probability of pga response with tapinarof compared with vehicle. relative risk and associated 95% cis were calculated using cochran-mantel-haenszel analyses, stratified by baseline pga score. relative risk indicates the probability of pga response occurring in the tapinarof group versus the probability of pga response occurring in the vehicle group. †non-caucasian category includes asian, black/african american, american indian or alaska native, native hawaiian, or other pacific islander, and other and has been grouped due to small patient numbers. itt, mi. mean proportion (se). pga response defined as a pga score of 0 (clear) or 1 (almost clear) with ≥2-grade improvement from baseline. bsa, body surface area; ci, confidence interval; itt, intention-to-treat; mi, multiple imputation; pga, physician global assessment; qd, once daily; se, standard error. tapinarof cream 1% once daily for plaque psoriasis: efficacy by baseline disease characteristics and demographics in two pivotal phase 3 trials leon kircik,1,2 linda stein gold,3 james del rosso,4 seemal r. desai,5,6 brad p. glick,7 howard sofen,8 anna m. tallman,9 david s. rubenstein,9 janine fournier,9 philip m. brown9 1skin sciences pllc, louisville, ky, usa; 2icahn school of medicine at mount sinai, new york, ny, usa; 3henry ford health system, detroit, mi, usa; 4jdr dermatology research/thomas dermatology, las vegas, nv, usa; 5university of texas southwestern medical center, dallas, tx, usa; 6innovative dermatology, plano, tx, usa; 7herbert wertheim college of medicine, florida international university, miami, fl, usa; 8david geffen ucla school of medicine, los angeles, ca, usa; 9dermavant sciences, inc., morrisville, nc, usa synopsis ■ tapinarof is a first-in-class, non-steroidal, topical therapeutic aryl hydrocarbon receptor modulating agent (tama) in development for the treatment of psoriasis and atopic dermatitis ■ in two identical, randomized, double-blind phase 3 trials, psoaring 1 and psoaring 2, tapinarof cream 1% once daily (qd) demonstrated highly statistically significant efficacy versus vehicle at 12 weeks and was well tolerated in adults with mild-to-severe plaque psoriasis1 objective ■ to present results for the pivotal phase 3 primary efficacy endpoint (proportion of patients who achieved a physician global assessment [pga] response at week 12) by baseline disease characteristics and demographics using pooled data from psoaring 1 and psoaring 2 methods study design ■ patients with mild-to-severe plaque psoriasis were randomly assigned 2:1 to receive tapinarof cream 1% qd or vehicle qd for 12 weeks in two identical, phase 3, multicenter (us and canada), double-blind, vehicle-controlled trials (figure 1) ■ following the double-blind period, patients could enroll in a separate open-label, long-term extension study for an additional 40 weeks of treatment, or complete a follow-up visit 4 weeks after the end of treatment (week 16) figure 1. study design *pga of 2 (mild) or 4 (severe) was limited to ~10% each of the total randomized population; ~80% of the randomized population had a pga of 3 (moderate). bsa, body surface area; pga, physician global assessment; qd, once daily; r, randomized. endpoints and statistical analysis ■ the primary endpoint was pga response at week 12, defined as the proportion of patients with a pga score of 0 (clear) or 1 (almost clear) and ≥2-grade improvement in pga score from baseline to week 12 ■ the incidence, frequency, and nature of adverse events (aes) and serious aes were monitored from the start of study treatment until the end-of-study visit ■ the pooled analyses used multiple imputation for the intention-to-treat (itt) populations in psoaring 1 and 2 ■ tapinarof cream 1% qd and vehicle groups were compared within each subgroup for the primary endpoint using 95% confidence intervals for the relative risk calculated using cochran-mantel-haenszel analyses stratified by baseline pga score results patient disposition and baseline characteristics ■ the pooled analysis population included 1,025 patients randomized to tapinarof cream 1% qd (n=683) or vehicle qd (n=342) in psoaring 1 and 2 (itt population) ■ baseline disease characteristics and demographics in the pooled population were comparable across treatment groups (table 1) ■ overall, at baseline, 82% had a pga score of 3 (moderate), 57% had psoriasis for >10 years, and 26% had ≥10% body surface area (bsa) affected table 1. baseline patient demographics and disease characteristics (pooled psoaring 1 and 2) tapinarof 1% qd (n=683) vehicle qd (n=342) age <65 years, n (%) 584 (85.5) 302 (88.3) male, n (%) 401 (58.7) 188 (55.0) race, n (%) caucasian 586 (85.8) 284 (83.0) asian 46 (6.7) 25 (7.3) black/african american 30 (4.4) 17 (5.0) american indian or alaska native 2 (0.3) 2 (0.6) native hawaiian or other pacific islander 1 (0.1) 1 (0.3) other* 13 (1.9) 10 (2.9) table 1. (cont) ■ figure 3 displays photographs of the clinical response of a patient treated with tapinarof cream who achieved the primary and secondary efficacy endpoints at week 12 figure 3. clinical response of a patient with plaque psoriasis who achieved primary and secondary efficacy endpoints at week 12 pga and pasi are global efficacy assessments. example of one representative target lesion of one tapinarof-treated patient from psoaring 1 clinical trial. individual results may vary. pasi, psoriasis area and severity index; pga, physician global assessment. safety ■ treatment-emergent aes (teaes) were mostly mild to moderate in severity, with a low rate of study discontinuation (5.6% in psoaring 1 and 5.8% in psoaring 2) ■ the most common teaes overall were folliculitis (20.2% tapinarof vs 0.9% vehicle), nasopharyngitis (5.7% tapinarof vs 4.4% vehicle), and contact dermatitis (4.8% tapinarof vs 0.3% vehicle) ■ although conclusions cannot be drawn due to the small number of patients in some subgroups, the frequency and type of aes appeared to be generally comparable across subgroups and consistent with those observed in the overall population conclusions ■ tapinarof cream 1% qd was consistently efficacious and well tolerated irrespective of baseline pga score, bsa affected, duration of psoriasis, sex, age, race, or country of enrollment (us or canada) ■ due to the small number of patients in some subgroups, limitations exist regarding the ability to draw definitive conclusions from the subgroup analysis ■ the consistent efficacy and tolerability in all subgroups support the potential use of tapinarof cream across a broad spectrum of disease severity and patient demographics ■ a long-term extension trial (psoaring 3) of intermittent treatment with tapinarof cream 1% qd based on pga score demonstrated continued efficacy following the 12-week pivotal trials and an ~4-month remittive effect off therapy2 ■ tapinarof cream 1% qd has potential to be the first topical psoriasis treatment with a novel mechanism of action in over 20 years references 1. lebwohl m, et al. n engl j med. 2021;385:2219–2229; 2. strober b, et al. innovations in dermatology virtual spring conference 2021, poster presentation, march 16–20, 2021. acknowledgments this study was funded by dermavant sciences, inc. the authors thank the participating investigators, patients and their families, and colleagues involved in the conduct of the study. l.k. has served as a consultant/speaker/investigator/advisory board member for abbott laboratories, abbvie, ablynx, aclaris, acambis, allergan, inc., almirall, amgen, inc., anacor pharmaceuticals, anaptys, arcutis, arena, assos pharma, astellas pharma us, inc., asubio, bausch health, berlex laboratories (bayer healthcare pharmaceuticals), biogen-idec, biolife, biopelle, bms, boehringer-ingleheim, breckinridge pharma, cassiopea, centocor, inc., cellceutix, cipher, coherus, colbar, combinatrix, connetics corporation, coria, dermavant sciences, inc., dermira, dermik laboratories, dow pharmaceutical sciences, inc., dr. reddy’s lab, dusa, embil pharmaceuticals, eli lilly, eos, exeltis, ferndale laboratories, inc., foamix, ferrer, galderma, genentech, inc., glaxosmithkline, plc, glenmark, health point, ltd, idera, incyte, intendis, innocutis, innovail, isdin, johnson & johnson, kyowakirin, laboratory skin care, inc., leo pharma, l’oreal, 3m, maruho, medical international technologies, merck, medicis pharmaceutical corp., merz, nano bio, novartis ag, noven pharmaceuticals, nucryst pharmaceuticals corp, obagi, onset, orthoneutrogena, pediapharma, pfizer, promius, puracap, pharmaderm, qlt, inc, quinnova, quatrix, regeneron, sanofi, serono (merck serono international sa), skinmedica, inc., stiefel laboratories, inc., sun pharma, taro, tolerrx, triax, ucb, valeant pharmaceuticals intl, warner-chilcott, xenoport and zage. l.s.g. has served as a consultant, and/or has received payment for the development of educational presentations, and/ or has received grants from arcutis, amgen, bristol myers squibb, dermavant sciences, inc., eli lilly, leo pharma, ortho dermatologic, and ucb biopharma. j.d.r. is an advisor and research investigator for dermavant sciences, inc. b.p.g. has served as an investigator/speaker/advisor for abbvie, brickell biotech, celgene, chemocentryx, corrona registry pso, corrona registry ad, dermavant sciences, inc, dermira, eli lilly, janssen, novartis, ortho dermatologics, pfizer, prose registry, regeneron, sanofi-genzyme, sun pharmaceutical industries, inc. h.s. has served as scientific adviser and/or clinical study investigator for abbvie, boehringer ingelheim, bristol myers squibb, dermavant, sciences inc., eli lilly, incyte, janssen, leo pharma, novartis, pfizer, sanofigenzyme, sun pharma and ucb. a.m.t., d.s.r, j.f., and p.m.b. are employees of dermavant sciences, inc., with stock options. editorial and medical writing support under the guidance of the authors was provided by apothecom, uk, and was funded by dermavant sciences, inc. in accordance with good publication practice (gpp3) guidelines (ann intern med. 2015;163:461–464). contact dr leon kircik at wedoderm@yahoo.com with questions or comments. adult patients with plaque psoriasis • aged 18–75 years old • pga score ≥2* • bsa ≥3%–≤20% double-blind treatment (12 weeks) 2:1 2:1 tapinarof 1% qd (n=340) tapinarof 1% qd (n=343) vehicle qd (n=170) vehicle qd (n=172) (n=510) (n=515) r r p ro p o rt io n o f p at ie n ts , % 19.9 5.8 0 2 (mild) 3 (moderate) 4 (severe) <10% ≥10% <5 years 5−10 years >10 years baseline pga bsa affected duration of disease 40.1 * 6.4 36.3 * 4.7 38.6 * 5.1 35.6 * 9.3 34.8 * 7.8 36.9 * 4.1 39.3 * 6.510 20 30 40 tapinarof 1% qd vehicle qd 50 60(a) p ro p o rt io n o f p at ie n ts , % 0 10 20 30 40 50 60(b) sex 38.5 5.3 male * female 36.9 7.2 * age <65 years 36.4 5.7 * ≥65 years 46.1 * 9.6 race (binary)† caucasian * 38.8 6.4 noncaucasian * 30.5 5.3 country of enrollment us * 36.1 6.0 canada * 42.9 6.5 tapinarof 1% qd vehicle qd • pga=3 • pasi=16.0 • pga=2 • pasi=5.5 • pga=1 • pasi=2.4 baseline week 4 week 12 microsoft word 13. 644 proof done.docx skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 79 brief articles subcutaneous panniculitis-like t-cell lymphoma: a case report david d. xiong, ba,1 brandon t. beal, md,2 manisha manmohan, md,2 m. georgina uberti, md,3 kathryn riley, md,2 anthony p. fernandez, md, phd2 1cleveland clinic lerner college of medicine, cleveland oh 2cleveland clinic foundation, department of dermatology, cleveland oh 3cleveland clinic foundation, departments of anatomic pathology and dermatology, cleveland oh subcutaneous panniculitis-like t-cell lymphoma (sptcl) is an unusual cutaneous t-cell lymphoma (tcl) accounting for <1% of non-hodgkin lymphomas which typically presents with subcutaneous nodules or deep plaques. we present the case of a woman diagnosed with sptcl successfully treated with oral corticosteroids and methotrexate. a woman in her 60s presented with a 4month history of numerous painful 4-8cm subcutaneous nodules on the cheeks, arms, breasts, and buttocks (figure 1a). her past medical history was unremarkable. review of symptoms was notable for fever, fatigue, and a 60-pound unintentional weight loss. biopsy of a lesion demonstrated a dense atypical lymphoid infiltrate in the subcutis (figure 2) that was cd3+, cd8+, cd56-, reactive for tia, perforin, granzyme b, and bf1, with rare cd20+ cells. tissue cultures and stains were negative. laboratory studies were notable for elevated lactate dehydrogenase (556 u/l), mildly elevated transaminases, and mild pancytopenia. flow cytometry analysis of peripheral blood was unrevealing. positron emission tomography demonstrated numerous subcutaneous nodules in her cheeks, arms, neck, breasts, back, mesentery, mediastinum, and abdominal cavity without lymphadenopathy or hepatosplenomegaly. the patient was diagnosed with sptcl and started on oral methotrexate and a prednisone taper with atrophy of her subcutaneous nodules and resolution of her elevated transaminases, cytopenias, and symptomatic improvement. she was continued on 15mg weekly methotrexate with introduction report of a case we present a case of a woman diagnosed with subcutaneous panniculitis-like t-cell lymphoma treated with prednisone and methotrexate with sustained symptom remission, suggesting that uncomplicated subcutaneous panniculitis-like t-cell lymphoma can be managed effectively without multiagent chemotherapy or radiation. abstract skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 80 sustained symptom remission 4 months after diagnosis (figure 1b). figure 1. (a) subcutaneous nodules on the bilateral breasts at presentation (b) and after four months of treatment with methotrexate and a prednisone taper figure 2. a dense, lobular lymphocytic panniculitis with rimming of the adipocytes by atypical t-cells. the lymphocytes demonstrate nuclear atypia, there is adipocyte membrane crowding and disruption, and cellular fat necrosis. 40x magnification. hematoxylin and eosin staining. sptcl is an uncommon tcl characterized by subcutaneous nodules that may be scattered across the body. cytologically, it is defined by a t-cell infiltrate expressing an αβ t-cell receptor phenotype and is typically characterized by a cd4-, cd8+, cd56-, bf1 lymphoid infiltrate. these lymphoid infiltrates are typically confined to subcutaneous tissue.1–3 sptcl has been associated with underlying autoimmune and rheumatologic disorders such as lupus erythematosus or rheumatoid arthritis in 20-40% of patients. associated symptoms may include fevers, chills, weight loss, fatigue, and myalgia. laboratory findings may include cytopenias and elevated liver function tests, and radiographic studies may demonstrate lymphadenopathy and hepatosplenomegaly. it may be accompanied by hemophagocytic syndrome (hps) in approximately 20% of patients, which portends a notably worse prognosis.3 though traditional therapy for sptcl has centered on multiagent combination chemotherapy, such as with chop (i.e. cyclophosphamide, adriamycin, vincristine, and prednisone) or chop-like regimens,4 these treatments are associated with significant morbidity, often surpassing that of the disease itself. thus, there has been a renewed push to induce disease remission with less toxic and immunosuppressive regimens such as systemic corticosteroids, methotrexate, and other more common immunosuppressive rather than chemotherapy regimens.2 response rates are similar to that of traditional chemotherapy, with the majority of patients achieving complete disease remission with immunosuppressive regimens such as systemic corticosteroids, sparing patients the cytotoxic side effects of traditional chemotherapy.1,5 multiagent chemotherapy may be reserved for patients who do not respond to systemic corticosteroids or patients with hps, with or without stem cell transplantation. radiotherapy may also be considered in cases of solely local disease.4 conflict of interest disclosures: none funding: none corresponding author: david d. xiong, ba cleveland clinic lerner college of medicine, cleveland clinic foundation. discussion skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 81 9500 euclid avenue, na2-90. cleveland oh, 44195. tel: (314) 435-7276 email: xiongd@ccf.edu references: 1. willemze r, jansen pm, cerroni l, et al. subcutaneous panniculitis-like t-cell lymphoma: definition, classification, and prognostic factors: an eortc cutaneous lymphoma group study of 83 cases. blood. 2008;111(2):838-845. doi:10.1182/blood-2007-04-087288 2. parveen z, thompson k. subcutaneous panniculitis-like t-cell lymphoma: redefinition of diagnostic criteria in the recent world health organization–european organization for research and treatment of cancer classification for cutaneous lymphomas. arch pathol lab med. 2009;133(2):303-308. doi:10.1043/1543-2165133.2.303 3. swerdlow s, campo e, harris n, jaffe e, pileri s, stein h. who classification of tumours of haematopoietic and lymphoid tissues, fourth edition. lyon, france: iarc; 2008. 4. go rs, wester sm. immunophenotypic and molecular features, clinical outcomes, treatments, and prognostic factors associated with subcutaneous panniculitis-like t-cell lymphoma. cancer. 2004;101(6):1404-1413. doi:10.1002/cncr.20502 5. guenova e, schanz s, hoetzenecker w, et al. systemic corticosteroids for subcutaneous panniculitis-like t-cell lymphoma. br j dermatol. 2014;171(4):891-894. doi:10.1111/bjd.13053 skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 304 research letter interviewing dermatology applicants in a virtual setting: a perspective after 2020-2021 match sydney a. weir bs 1, reagan hattaway bs 1, nikhi p. singh bs1, timothy w. king md, phd2, lauren c. s. kole md3 1 school of medicine, university of alabama at birmingham, birmingham, al 2 department of surgery, division of plastic and reconstructive surgery, loyola medicine, chicago, il 3 department of dermatology, university of alabama at birmingham, birmingham, al the covid-19 pandemic greatly affected the 2020-2021 residency application cycle. in the spring of 2020, the association of american medical colleges (aamc) and dermatology residency program directors released statements discouraging visiting medical student sub-internships and in-person interviews.1,2 the aamc has since recommended the resumption of subinternships in august 2021. however, all specialties conducted interviews virtually in 2021.3 in 2020, residency programs across the country, including dermatology, created social media accounts, and implemented virtual open houses.4 it is unclear whether these methods effectively evaluated and recruited applicants. we aimed to assess the impact of visiting rotations, pre-interview events, and virtual interviews through the lens of dermatology program directors and medical students who matched into dermatology in 2021. an online survey was distributed to all 138 dermatology residency program directors in the united states from may 4, 2021, to june 10, 2021, by email. the survey was intended for program directors, faculty, and medical students. questions for program directors and medical students aimed to capture views on visiting rotations, virtual interviews, and the effectiveness of virtual pre-interview events. we had a response rate of approximately 13% (n=18). in addition to dermatology program director responses, we received a 2% response rate from medical students who successfully matched into dermatology during the 2020-2021 application cycle (n=11). medical student responses were omitted from the final analysis as they were not likely reflective of the medical student population. with regards to away rotations, most pd respondents (72%) believed applicants missed out on fully experiencing their programs by forgoing in-person away rotations and interviews. additionally, most pd respondent (68%) believed the absence of a student’s away rotation would limit their ability to gauge an applicant. as shown in figure 1, q&a sessions with residents and virtual open houses were the most frequently offered pre-interview events (21% and 19%, respectively). pd respondents rated virtual open houses as the most virtual pre-interview event (average rating of 6.8 skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 305 figure 1. this figure shows which virtual pre-interview events were offered during the 2020-2021 application cycle as reported by program directors. q&a sessions with residents were the most offered event by program directors followed closely by virtual open houses. figure 2. the survey asked program directors to rank the effectiveness of all virtual pre-interview events they offered from 1-10, 10 being the most effective. columns reflect individual respondents' answers. each event received highly variable effectiveness scores. “virtual open houses”, “q&a session with residents”, and “virtual facility tour” had the most responses. of those three, virtual open houses had the highest average score.*average effectiveness scores for the virtual events with the most responses. skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 306 out of 10, shown in figure 2). further, 44% of program directors reported developing accounts on social media platforms after march 1, 2020, mainly “to promote our residency program or department/division.” our study suggested that the lack of away rotations had a large impact on a dermatology residency program’s ability to evaluate applicants. our results further illustrate that virtual q&a sessions with residents and virtual open houses were the most popular and effective opportunities for residency programs to offer students. dermatology residency training programs may use this information to decide which virtual pre-interview events to offer in subsequent virtual application cycles. furthermore, with the possibility of a return to an in-person interview season in the future, there may be a role for a hybrid application process.5 as costs of applying to competitive specialties, such as dermatology, continue to increase, the decreased cost burden associated with virtual platforms may prove beneficial.6 this study has limitations, including its retrospective nature and small sample size. further, unverified and incomplete responses limited the generalizability of our results, as there were incomplete data for some questions. residency programs and applicants adapted to the virtual application cycle through enhanced virtual interaction, and these opportunities appeared to impact the application cycle in nuanced ways. a significant downside to this virtual transition is decreased interpersonal interactions between parties. it is unclear what future application cycles hold, however, our study’s findings may provide a framework for the continued use of virtual opportunities in the wake of a global pandemic. conflict of interest disclosures: none funding: none corresponding author: lauren c.s. kole md university of alabama at birmingham school of medicine department of dermatology 510 20th st s birmingham, al 35233 email: laurenkole@uabmc.edu references: 1. association of american medical colleges. specialty response to covid-19. assoc am med coll. https://studentsresidents.aamc.org/applyingresidency/article/specialty-response-covid-19/ 2. dermatology residency program director consensus statement on 2020-21 application cycle. https://aamcorange.global.ssl.fastly.net/production/media/fil er_public/0f/7b/0f7b547e-65b5-4d93-8247951206e7f726/updated_dermatology_program _director_statement_on_202021_application_cycle 3. kamangar f, davari p, azari r, et al. the residency interview is still paramount: results of a retrospective cohort study on concordance of dermatology residency applicant evaluators and influence of the applicant interview. dermatol online j. 2017;23(5):13030/qt7rf0x11c. 4. singh np, fang h, lopez r, deatkine ab, burns z, boyd cj. thoughts on 2021-2022 visiting rotation recommendations from current and recent applicants in surgery. the american journal of surgery. march 2021. pmid: 33810835. 5. rosman is, schadt cr, samimi ss, rosenbach m. approaching the dermatology residency application process during a pandemic. j am acad dermatol. 2020;83(5):e351e352. doi:10.1016/j.jaad.2020.07.066 6. murphy b. without travel, costs of residency interviews to decline sharply. american medical association. https://www.amaassn.org/residents-students/residency/withouttravel-costs-residency-interviews-declinesharply. published june 29, 2020. accessed october 13, 2021 mailto:laurenkole@uabmc.edu https://students-residents.aamc.org/applying-residency/article/specialty-response-covid-19/ https://students-residents.aamc.org/applying-residency/article/specialty-response-covid-19/ https://students-residents.aamc.org/applying-residency/article/specialty-response-covid-19/ https://aamc-orange.global.ssl.fastly.net/production/media/filer_public/0f/7b/0f7b547e-65b5-4d93-8247-951206e7f726/updated_dermatology_program_director_statement_on_2020-21_application_cycle https://aamc-orange.global.ssl.fastly.net/production/media/filer_public/0f/7b/0f7b547e-65b5-4d93-8247-951206e7f726/updated_dermatology_program_director_statement_on_2020-21_application_cycle https://aamc-orange.global.ssl.fastly.net/production/media/filer_public/0f/7b/0f7b547e-65b5-4d93-8247-951206e7f726/updated_dermatology_program_director_statement_on_2020-21_application_cycle https://aamc-orange.global.ssl.fastly.net/production/media/filer_public/0f/7b/0f7b547e-65b5-4d93-8247-951206e7f726/updated_dermatology_program_director_statement_on_2020-21_application_cycle https://aamc-orange.global.ssl.fastly.net/production/media/filer_public/0f/7b/0f7b547e-65b5-4d93-8247-951206e7f726/updated_dermatology_program_director_statement_on_2020-21_application_cycle https://aamc-orange.global.ssl.fastly.net/production/media/filer_public/0f/7b/0f7b547e-65b5-4d93-8247-951206e7f726/updated_dermatology_program_director_statement_on_2020-21_application_cycle untitled synopsis: 1. a review of two cases of recalcitrant dermatophytosis which highlight a growing community health concern of antifungalresistant trichophyton species. 2. highlight important clinical and diagnostic findings to consider when treating antifungal resistant dermatophytosis. 3. utilization of fungal culture and antifungal susceptibility testing is imperative to aggressively treat and halt the spread of multidrug resistant tinea, especially for those with recurrent disease.. patient a 24-year-old male with a 5+ year history of persistent dermatophytosis. • exam findings: erythematous scaly plaques with central areas of clearing and active borders on the buttocks, left elbow, right hand, face. (figure 1.1) • social history: lived part-time in india and extensive intercontinental travel history for work • prior work-up: previous biopsies showed dermatophytosis. no fungal culture had been sent per medical record review. • failed treatments: several courses of oral terbinafine prescribed over 5 years. • on initial exam, skin scraping with koh was inconclusive. fungal culture was sent and grew t. mentagrophytes type viii. • speciation and susceptibility reported in table 1 highlighting terbinafine resistance. • patient was treated with fluconazole 200 mg daily, econazole 2% cream, & ciclopirox shampoo. conclusion there is a growing concern regarding the increase in the incidence of resistance development of dermatophytes against terbinafine. the presented cases illustrate the growing epidemiological trend of antifungalresistant dermatophytosis in the us. these cases illustrate the growing epidemiological trend of antifungalresistant dermatophytosis. this warrants a change in dermatologists’ clinical practices to 1) consider drug resistance in recalcitrant cases of dermatophytosis 2) evaluate the utility of fungal culture and interpreting antifungal susceptibility testing to isolate resistant species 3) practice antifungal stewardship and treat aggressively. patient b 46-year-old male with a 10+ year history of recalcitrant dermatophytosis. • exam findings: erythematous scaly coalescing papules and plaques with active erythematous borders on the posterior thighs, abdomen, buttocks (figure 2.1) • prior failed treatments: terbinafine, itraconazole, fluconazole without improvement. • fungal cultures grew t. rubrum, figure 2.2 • speciation and susceptibility: reported in table 2 revealed terbinafine, itraconazole, and fluconazole resistance. posaconazole and griseofulvin susceptible. • additional failed treatment: griseofulvin 250 mg three times daily x 3 months • secondary treatment: posaconazole 300 mg daily x 6 weeks. figure 1.1 patient a: buttocks and left shoulder references terbinafine-resistant dermatophytosis in alabama: two cases of recalcitrant dermatophytosis and the dermatologist’s role in detection of drug resistance and antifungal stewardship callie hill md1, mahmoud ghannoum phd3 , natalie garcia ms 2, boni elewski md1 university of alabama at birmingham hospital, department of dermatology 1 university of alabama at birmingham, school of medicine 2 university hospitals cleveland medical center3 table 1. susceptibility report with minimum inhibitory concentrations (mic) (μg/ml) for patient a highlighting t. mentagrophytes resistance to terbinfafine . figure 2.1 patient b: lower abdomen and posterior thighs table 2. susceptibility report with minimum inhibitory concentrations (mic) (μg/ml) for patient b highlighting t. rubrum resistance to terbinafine, itraconazole, and fluconazole (2019-936). . introduction we define recalcitrant dermatophytosis as insufficient response to an adequate antifungal course in a patient with microscopy or culture proven tinea infection. • new species, including t. mentagrophytes type viii, are spreading worldwide, initially from india and now reported in birmingham, al.1 • innate terbinafine resistance vs. the widespread use of corticosteroids and topical antifungals in india is theorized to have resulted in t. mentagrophytes • single nucleotide polymorphisms (snps) in the squalene epoxide (se) gene in trichophyton species leads to terbinafine resistant isolates • evolving drug resistant dermatophyte species and lack of new treatments pose an increasing public health burden.2 • the minimum inhibitory concentration (mic) is defined as the lowest concentration of a drug which inhibits microorganism growth. • the clinical and laboratory standards institutes (clsi) has not published standardized guidelines for antifungal resistance in dermatophytes. however, a mic of >0.5 μg/ml for terbinafine is considered elevated.3 ○ the break points for itraconazole against candida species are as followed: mic of ≤0.125 μg/ml is considered susceptible, 0.25 to 0.5 is susceptible dose dependent and greater or equal to 1 is resistant. ○ the break points for fluconazole against candida species are as followed: mic of ≤8 μg/ml is susceptible, 16-32 μg/ml is susceptible dose dependent and greater or equal to 64 is resistant.4 current systemic antifungal treatment options • terbinafine 250 mg daily • fluconazole 200 mg daily • itraconazole 200 mg daily • griseofulvin (ultramicronized) 300-375 mg/daily • posaconazole (off-label) 300mg daily **add topical antifungals from a different class. if oral azoleuse topical allylamine (terbinafine) or ciclopirox. figure 1.2: fungal culture growing t. mentagrophytes type viii on potato agar figure 2.2: fungal culture growing t. rubrum on potato agar 1. ebert a, monod m, salamin k, burmester a, uhrlaß s, wiegand c, hipler uc, krüger c, koch d, wittig f, verma sb, single a, gupta s, vasani r, saraswat a, madhu r, panda s, das a, kura mm, kumar a, poojary s, schirm s, gräser y, paasch u, nenoff p. alarming india-wide phenomenon of antifungal resistance in dermatophytes: a multicentre study. mycoses. 2020 jul;63(7):717-728. doi: 10.1111/myc.13091. epub 2020 may 4. pmid: 32301159.saunte, ditte m. .., et al. “emerging terbinafine resistance in trichophyton: clinical characteristics, squalene epoxidase gene mutations, and a reliable eucast method for detection.” antimicrobial agents and chemotherapy, vol. 63, no. 10, american society for microbiology, 2019, https://doi.org/10.1128/aac.01126-19. 2. taghipour s, shamsizadeh f, pchelin im, rezaei-matehhkolaei a, zarei mahmoudabadi a, valadan r, ansari s, katiraee f, pakshir k, zomorodian k, abastabar m. emergence of terbinafine resistant trichophyton mentagrophytes in iran, harboring mutations in the squalene epoxidase (sqle) gene. infect drug resist. 2020 mar 13;13:845-850. doi: 10.2147/idr.s246025. pmid: 32214830; pmcid: pmc7078656. 3. barros, maria elisabete da silva, et al. “evaluation of susceptibility of trichophyton mentagrophytes and trichophyton rubrum clinical isolates to antifungal drugs using a modified clsi microdilution method (m38-a).” journal of medical microbiology, vol. 56, no. 4, soc general microbiol, 2007, pp. 514–18, https://doi.org/10.1099/jmm.0.46542-0. 4. clinical and laboratory standards institute (2002). reference method for broth dilution antifungal susceptibility testing of filamentous fungi, approved standard m38-a. wayne, pa: clinical and laboratory standards institute table 2: mic (μg/ml) and fici results of t. mentagrophytes against itraconazole, fluconazole and combination of itraconazole and fluconazole. https://doi.org/10.1128/aac.01126-19 https://doi.org/10.1099/jmm.0.46542-0 patients with atopic dermatitis (scorad 30) using the tested cleanser once a day during 14 days showed a significant reduction of their scorad and local scorad associated with an increase of their bacterial diversity (shannon index) and a reduction of staphylococci level (both s. epidermis and s. aureus). these results indicated that this syndet is useful for patients suffering from atopic dermatitis and can reduce the skin microbiota dysbiosis associated with this pathology. however, use of an adapted emollient (supplemented with the same biomass (1)) in addition to syndet is important for atopic patient’s management. s. seite, d. moyal la roche-posay dermatological laboratories, asnières, france objective methodology using a specific cleanser for patients with mild atopic dermatitis relationship between clinical efficacy and skin microbiota modification changes in the composition of microbial communities that colonize skin have been linked to several dermatological diseases, in particular atopic dermatitis. this pathology has long been associated with staphylococcus aureus colonization or infection. we speculated that a mild cleanser (syndet) supplemented with a biomass of non-pathogenic bacteria such as vitreoscilla filiformis, grown in a medium containing thermal spring water (lrp-vfb) could have a clinical effect on the skin symptoms and skin bacterial landscape. a double blind study was conducted with 32 atopic dermatitis patients using the mild cleanser once a day during 14 days. scorad, local scorad, clinical and subjective signs, tolerance and quality of life (dlqi) have been evaluated before and after treatment. swabs were taken under axenic conditions, from lesion and proximal unaffected skin to analyse microbiome. 16s rrna bacterial gene was used to analyze the composition of bacterial communities. results when looking at the results obtained on the 32 patients included in this study, a significant improvement of scorad was obtained after treatment. for local scorad, significant improvement of erythema, desquamation and pruritus was noticed. a good to excellent efficacy was noted for 53% of patients and a good to excellent tolerance for 62%. at the same time, a significant improvement in the quality of life with a reduction of the dlqi of 27% was evidenced. using a high-throughput sequencing approach that targets a portion of the 16s rrna gene and comparing an affected area and a closest non affected area for each participant, we obtained results for 19 individuals (13f and 6m aged 36 ± 15 years duration of ad: 8 ± 9 years) with 38-paired samples analysed. mean scorad at d0 for these patients was 30 ± 5 and at d14, 22 ± 12 (p<0.05, -26%, 14 responders). local scorad for affected areas evaluated in the 14 responders was in average 6,5 ± 1,6 at d0 and 3,4 ± 1,5 at d14 (p<0.05). conclusion reference bacterial biodiversity (shannon index) shannon index measuring the bacterial biodiversity was lower at d0 on the affected (af) skin compared to the adjacent unaffected (uaf) skin. it increased significantly after treatment and became similar on both areas (d14). shannon index n=19 d0 uaf af d14 uaf af 1,89 1,75 2,26* 2,28** 0,70 0,55 0,58 0,52 0,11 0,09 0,10 0,08 *p=0,015; **p=0,004 vs d0 s h an n o n in d ex 3,5 3 2,5 2 1,5 1 0,5 0 d0-af d14-af d0-uaf d14-uaf bacterial landscape average taxonomic composition (30 main genus) of the skin microbiome associated with ad prior (d0) and after (d14) treatment associated with unaffected (uaf) and affected (af) showed that the reduced disease severity was associated with a significant decrease of staphylococcus in both areas (from 22 to 12% (p=0.028) in uaf and from 28.5 to 16% (p=0.022) in af). staphylococcus species a decrease of both s. epidermis and s. aureus was noticed after treatment. 2000 d14-uaf d0-uaf d14-af d0-af 0 4000 6000 8000 10000 12000 23/456789899:1".4;0.<=;0;1" d14-uaf d0-uaf d14-af d0-af 0 500 1000 1500 2000 2500 3000 3500 staphylococcus epidermis staphylococcus aureus seite s, zelenkova h, martin r. clinical efficacy of emollients in atopic dermatitis patients relationship with the skin microbiota modification. clin cosm invest dermatol: 2017, janv 12: 10: 25-33 reads reads propiobacterium micrococcus corynebacterium 1 unclassified bergeyella peptoniphilus brevibacterium veillonella staphylococcus paracoccus lactobacillus finegoldia brevundimonas corynebacterium microbacterium fusobacterium uncultured bacterium kocuria methylobacterium herbaspirillum granulicatella streptococcus clostridium sensi stricto 3 anaerococcus lactococcus gemella neisseria sphingomonas chryseobacterium clostridium sensu stricto 1 mean sd sem fc17posterlarochemoyalcleanserforatopicdermatitis.pdf skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 750 skinmages a friable, polypoid tumor on the chest catherine c. motosko, md1, gabriel villada, md2, fleta bray, md1, gregory perez, md1,3 1 dr. phillip frost department of dermatology and cutaneous surgery, university of miami miller school of medicine, miami, fl 2 department of pathology, miami va healthcare system, miami, fl 3 department of dermatology, miami va healthcare system, miami, fl a 90-year-old man with a history of bccs and sccs presented in clinic complaining of a tender, enlarging growth on his left upper chest that had been present and growing over 2–3 years. the lesion would bleed with minimal trauma or manipulation. on the left upper chest was a 6x8cm, tender, erythematous, exophytic, friable chest tumor without accompanying regional adenopathy. shave biopsy demonstrated dermal islands of atypical basaloid cells with pushing borders and central areas of necrosis en masse. numerous mitoses, including atypical forms, were observed. focal squamous cell differentiation and clear cell changes were present. lesional cells stained strongly positive for cam5.2. porocarcinoma (malignant poroma) is a rare, high grade cutaneous adnexal malignancy of the sweat glands. while the exact incidence is unknown, it is thought to represent between 0.005–0.01% of cutaneous malignancies. tumors tend to occur on the lower extremities, trunk, or head and neck of skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 751 the elderly, presenting as verrucous plaques or polypoid growths, which may bleed with minor trauma. histopathologically the neoplasm consists of dermal nests and islands of basaloid cells with pushing or infiltrative borders. cytologic features of malignancy can vary from moderate to marked and include cellular and nuclear polymorphism, hyperchromasia and atypical mitoses. necrosis en masse, perineural and lymphovascular invasion are variably present. ductal differentiation, or the presence of a precursor lesion (in-situ component, remnants of benign poroma), when present, facilitate the diagnosis of porocarcinoma. additional patterns can be seen, including clear cell changes, squamous cell differentiation, sarcomatoid transformation, intratumoral melanin deposition or melanocytic colonization, and presence of other lines of adnexal differentiation. although porocarcinoma has no specific immunophenotypic profile, immunohistochemistry can assist in the diagnosis in several settings. if the tumor has prominent squamous cell differentiation, ck7, cam5.2 or cea highlight ductal differentiation, therefore supporting the diagnosis of porocarcinoma versus squamous cell carcinoma.1 in the distinction between a primary adnexal tumor and adenocarcinoma metastatic to the skin, the former may express d2-40 and p63.2 finally, preliminary data suggest that a panel consisting of p16, p53, and rb can help differentiate porocarcinoma from benign poroma.3 treatment is typically with wide surgical excision, though mohs micrographic surgery has been an effective way of achieving complete removal. there is a high rate of recurrence after resection, with potential for metastasis to regional lymph nodes, and less commonly, internal organs. excision prior to locoregional metastasis improves survival. metastatic disease has proven resistant to currently available chemotherapies. the use of radiation therapies remains controversial. ct of the chest, abdomen, and pelvis demonstrated tumor of the left upper chest extending from the epidermis into the subcutaneous fat, with no apparent involvement of the underlying muscle or of metastatic disease. the patient was treated with wide local resection. he has since been placed on niacinamide, acitretin, and vismodegib for prevention and treatment of sccs and bccs. conflict of interest disclosures: none funding: none corresponding author: catherine c. motosko, md university of miami miller school of medicine dr. phillip frost department of dermatology and cutaneous surgery email: catherine.motosko@gmail.com references: 1. mahalingam m, et al. an immunohistochemical comparison of cytokeratin 7, cytokeratin 15, cytokeratin 19, cam 5.2, carcinoembryonic antigen, and nestin in differentiating porocarcinoma from squamous cell carcinoma. hum pathol. 2010;43:1265-1272. 2. plaza ja, et al. value of p63 and podoplanin (d2-40) immunoreactivity in the distinction between primary cutaneous tumors and adenocarcinomas metastatic to the skin: a clinicopathologic and immunohistochemical study of 79 cases. j cutan pathol. 2010;37:403-410. 3. zahn j, et al. altered rb, p16, and p53 expression is specific for porocarcinoma relative to poroma. j cutan pathol. 2019;46:659-664. skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 621 brief article multidisciplinary surgical management of extensive basal cell carcinomas marie vu, bsa1, tue felix nguyen, bs1, melinda lue, ba1, john browning, md2 1ut health san antonio long school of medicine, san antonio, tx 2department of dermatology, ut health san antonio, san antonio, tx a 40-year-old uninsured, white female presented to the student-run free clinic with multiple nodules on her left preauricular area and an ulcer in her glabella. the patient first noticed the nodules two years prior to her visit when they initially appeared as small papules. the lesions have enlarged over time, and she has had no associated bleeding or pain. the patient had no vision changes, dry eyes, or excessive tearing. she reported intermittent bleeding and drainage from the ulcer and has had no treatment or interventions for the lesions. the patient reported delaying treatment over the last two years due to a lack of insurance and dermatologic accessibility. on physical examination, a sclerotic hypopigmented plaque surrounded by multiple pearly pedunculated nodules with telangiectasias was observed on the left pre-auricular area (figure 1). the largest nodule measured to be 15 mm in diameter. an additional 15x20mm ulcer with brown crust on the inferior border was appreciated at the glabella (figure 2). histopathology of the lesions revealed aggregates of basaloid cells with hyperchromatic nuclei and scant cytoplasm, some of which were connected to the undersurface of the epidermis. the aggregates exhibited peripheral palisading nuclei embedded in a fibrotic and myxoid stroma. a diagnosis of infiltrative and nodular basal cell carcinoma (bcc) was made. abstract basal cell carcinoma (bcc) is the most common malignancy that can cause local tissue destruction. while treatment options for bcc vary depending on the degree of malignant progression, surgical intervention is generally required when there is significant tissue involvement. we present a case of a 40-year-old woman with extensive bccs requiring a multidisciplinary surgical approach for treatment. our case highlights the importance of utilizing a multidisciplinary team as well as different surgical management options for late stage bccs. case report skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 622 figure 1. sclerotic hypopigmented plaque surrounded by multiple pearly pedunculated nodules with telangiectasias. figure 2. 15x20mm ulcer with brown crust on the inferior border on the glabella due to the patient’s insurance status, a multidisciplinary team was accessed through a financial assistance program affiliated with the local teaching hospital. workup with computer tomography (ct) imaging revealed a 2mm osseous invasion of the right medial frontal sinus wall. a multidisciplinary team consisting of dermatology, radiation/oncology, otolaryngology-head and neck plastic surgery, ophthalmic plastic surgery, and oral and maxillofacial surgery recommended staged surgical excision and reconstruction after determining the bcc was stage t4a according to the american joint committee on cancer guidelines. three surgeries were scheduled to address the infiltrative and nodular bccs, respectively. the first surgery consisted of a wide local excision of the infiltrative bcc at the glabella and right medial eyelid, including resecting the medial nasal/lacrimal bone and anterior table of the frontal sinus bone. this procedure included reconstruction of an anterior table defect along with the medial and lateral canthus prior to closing with a left paramedian forehead flap (pmff) (figure 3). figure 3. closure with a left paramedian forehead flap. skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 623 the patient recovered without complications and returned two and a half weeks later for the second surgery. the second procedure consisted of a wide local excision of the left preauricular skin, a left superficial parotidectomy, and left modified radical neck dissection due to the extent of tumor invasion. a split-thickness skin graft from the right forearm was utilized for closure. the patient recovered without complications and returned a week later for the last procedure, which consisted of a division and inset of the left paramedian forehead flap. the patient recovered well and had no complaints at oneweek post-operative follow-up. bcc is the most common malignancy.1 while typically indolent, it may cause local invasion and destruction of adjacent tissue if treatment is delayed. thus, early recognition and intervention are essential to minimize complications and disfigurement. in choosing a treatment plan for bcc, several factors must be considered, including the cancer stage and area involved. mohs micrographic surgery is an option which involves precise surgical technique and complete excision of skin cancer that is checked by microscopic margin control. this technique confers benefits of reduced morbidity, decreased loss of function, and more favorable aesthetic outcome due to the reduced volume of tissue removed while maintaining clear margins.2 after excision, reconstructive procedures can restore appearance, facial symmetry, and function. for simpler superficial defects with an adequately vascularized wound bed, skin grafting can be used for reconstruction. split thickness skin grafts (stsg) include the epidermis and part of the dermis. compared to full thickness skin grafts, stsg are advantageous with more uniform thickness, less contracture, and more favorable take due to lower metabolic needs.3 for larger, complex deformities of the face, paramedian forehead flaps (pmff) are often employed. a vertical flap of skin and subcutaneous tissue is elevated from the forehead and rotated 180o to the region of defect. pmff are useful for closing nasal deformities, restoring breathing, and rebuilding nasal landmarks. the incorporation of the subcutaneous tissue in pmff allows replacement of volume lost during tumor resection and can be debulked and contoured to define landmarks.4 this procedure has low morbidity because the pedicled flap receives a robust vascular supply from the supratrochlear artery with multiple collaterals.5 primary closure of the donor site incision can usually be achieved without difficulty, and the local facial donor site allows excellent texture and color match.5 as seen in this case, there have been other reported cases of advanced skin neoplasms requiring a multidisciplinary approach.6 different causes of delay in diagnosis may be attributed to fear of diagnosis and treatment, inadequate access to care, lack of health literacy, and inadequate hygienic culture. this case calls for the importance of accessibility to dermatologic care. the patient reported she delayed diagnosis due to lack of insurance and inability to pay for an office visit. despite making up 27% of the general population, only 5% of uninsured patients make up the prevalence of patients at dermatology practices.7 this disparity highlights the significant barriers uninsured individuals may have with accessing dermatologic care. in addition, homeless and uninsured individuals are presumed to have a higher prevalence of skin cancer than the general population.8 as highlighted in this case, delayed detection of bcc may lead to a more invasive treatment requiring multidisciplinary teams for management. discussion skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 624 conflict of interest disclosures: none funding: none corresponding author: marie vu, bsa ut health san antonio long school of medicine 7703 floyd curl dr. san antonio, tx 78229 phone: (281) 617-8912 email: vum1@livemail.uthscsa.edu references: 1. marzuka ag, book se. basal cell carcinoma: pathogenesis, epidemiology, clinical features, diagnosis, histopathology, and management. yale j biol med. 2015;88:167-179. 2. malec k, brzewski p, cenda p, et al. extensive, neglected basal cell carcinoma of the half of the face-surgical treatment and reconstruction with an anterolateral microvascular thigh flap. postepy dermatol alergol. 2016;33:235-238. 3. braza me, fahrenkopf mp. split-thickness skin grafts. in: statpearls. treasure island (fl): statpearls publishing; may 8, 2022. 4. hammer d, williams f, kim r. paramedian forehead flap. atlas oral maxillofac surg clin north am. 2020;28(1):23-28. 5. smart rj, yeoh ms, kim dd. paramedian forehead flap. oral maxillofac surg clin north am. 2014;26(3):401-410. 6. varga e, korom i, raskó z, et al. neglected basal cell carcinomas in the 21st century. j skin cancer. 2011;2011:392151. 7. resneck js jr, isenstein a, kimball ab. few medicaid and uninsured patients are accessing dermatologists. j am acad dermatol. 2006;55:1084-1088. grossberg al, carranza d, lamp k, et al. dermatologic care in the homeless and underserved populations: observations from the venice family clinic. cutis. 2012;89:25-32. skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 229 research letter second primary malignancies after initial cutaneous angiosarcoma: a seer population-based study vignesh ramachandran, md1, asad loya, md2, kevin phan, md3,4 1 department of dermatology, new york university, new york, ny 2 department of ophthalmology, baylor college of medicine, houston, tx 3 department of dermatology, liverpool hospital, sydney, australia 4 university of new south wales, sydney, australia conic and colleagues1 provide an important epidemiologic study of cutaneous angiosarcomas (cas) using the national cancer institute’s surveillance, epidemiology, and end results (seer) database. they describe incidence rates and survival outcomes based on age, disease extent, and treatment. however, an important epidemiologic consideration after initial cas is the risk of second primary malignancies (spms). spms may have implications on surveillance post-cas diagnosis and prognosis. abstract introduction: the epidemiology of second primary malignancies is an under-investigated domain within dermatology. this notion is particularly true for more uncommon cutaneous oncologic diseases. while general epidemiological characteristics and survival data of patients with cutaneous angiosarcoma have been reported before, there is no investigation of the incidence and types of second primary malignancies (spms) that these patients face, which has relevance to screening and surveillance. methods: the national cancer institute’s surveillance, epidemiology, and end results (seer) database was utilized in this study. initial cases of cas were extracted and analyzed using standardized incidence ratios (sir) and excess absolute risks (ear) for spms relative to a control population, which was matched by sex, race (white/unknown, black, other), age group (5-year interval), and calendar year (5-year interval). ear was calculated per 10,000 persons. p-value <0.05 was deemed statistically significant. results: compared to a matched cohort from the general population, patients with cas demonstrated increased incidence of new malignancies (sir 1.54; 95% ci, 1.05-2.17; ear 107.02). specifically, there was increased risk of soft tissue malignancies, and non-epithelial skin malignancies other than melanoma/basal cell/squamous cell. discussion: spms may be linked to many etiologies, including genetic susceptibility, treatmentrelated sequelae, lifestyle/environmental factors, or shared risk factors. indefinite treatments may induce spms. recently, immunotherapy/immune-modulating drugs have been used to treat cas4; this therapy may increase the risk of spms via immunosuppression. shared etiology (i.e. blood vessel or soft tissue-derived neoplasms) may also explain spms observed. importantly, cas is associated with high recurrence even after complete resection. introduction skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 230 to address this question, we used the seer 18 dataset, which pools cancer incidence and survival data from 34.6% of the u.s. population.2 initial cases of cas (2000-2016) were extracted using the international classification of diseases for oncology 3rd edition (icd-o-3) histology code 9120/3 (“hemangiosarcoma”). skin sites were isolated using icd-o-3 topographical code c44.0-c44.9 (all skin sites). standardized incidence ratios (sir) and excess absolute risks (ear) were computed for spms relative to a control population, which was matched by sex, race (white/unknown, black, other), age group (5year interval), and calendar year (5-year interval). ear was calculated per 10,000 persons. p-value <0.05 was deemed statistically significant. overall, 358 cas cases were extracted. of these, 8.9% (32/358) developed spms. mean follow-up period was 39.4 (+/40.8) months and mean age at diagnosis of first neoplasm was 74.6 (+/13.0) years. at study end, 31.8% of the cohort remained alive. compared to a matched cohort from the general population, patients with cas demonstrated increased incidence of new malignancies (sir 1.54; 95% ci, 1.05-2.17; ear 107.02) (table 1). specifically, there was increased risk of soft tissue malignancies, and non-epithelial skin malignancies other than melanoma/basal cell/squamous cell. of the soft tissue spms, 75% (3/4) were blood vessel neoplasms (2 angiosarcomas, 1 malignant epithelioid hemangioendothelioma) and 25% (1/4) was sarcoma (sarcoma, nos). of the nonepithelial skin malignancies other than melanoma/basal cell/squamous cell spms, 100% (8/8) were angiosarcomas. the mechanisms underlying the association of cas with spms remain unclear. it is known that underlying risk factors for cas include radiation therapy as well as exposure to arsenic, polyvinyl chloride and viral hepatitis.3 however, these are also common risk factors for various other cancers. of note, in our study the risk was highest for non-epithelial skin cancers as highest risk of spms in patients with initial cas. we postulate this risk may also be partly attributed to treatment-related sequelae, such as chemotherapy and radiation. for cas, there is no clear treatment regimen; surgical resection appears to be the mainstay, and some patients receive adjuvant radiation therapy or chemotherapy.4 these indefinite treatments may induce spms. recently, immunotherapy/immunemodulating drugs have been used to treat cas;4 this therapy may increase the risk of spms via immunosuppression. furthermore, the literature reveals that particular mutations and pathophysiologic pathways may be implicated in angiosarcomas (e.g. kdr, tp53, and pik3ca. pik3ca).5 it is plausible that these pathways may be implicated in spms in patients with initial cas as they serve as a genetic predisposition that may become unmasked, especially when the spm is of vascular etiology. future studies would benefit from collaboration with translational researchers to elucidate the genetic sequencing and molecular characterization of malignant tissue in these patients via bio-banking. this may lead to more targeted therapy options methods results discussion skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 231 for the management of this challenging malignancy as well. the angiosarcoma project, for instance, is an example of such an effort.5 our analysis of cas within the seer database is constrained by several limitations. we were unable to study the tumor site, tumor characteristics, type of treatment received, and socioeconomic factors. additionally, lifestyle/modifiable risk factors cannot be assessed through seer, which also limited our analysis. data entry errors and physician-dependent factors (e.g. surgical technique) are also unable to be accounted for. in conclusion, patients who have been diagnosed with cas should be continuously monitored post initial diagnosis and treatment not only for recurrence but also for spms. conflict of interest disclosures: none funding: none corresponding author: vignesh ramachandran, md department of dermatology, new york university ambulatory care center, 11th floor, room 11-84 240 east 38th street, new york, ny 10016 phone: 212-263-5313 fax: 212-263-8752 email: vignesh.ramachandran@nyulangone.org references: 1. conic rrz, damiani g, frigerio a, tsai s, bragazzi nl, chu tw, mesinkovska na, koyfman sa, joshi np, budd gt, vidimos a, gastman br. incidence and outcomes of cutaneous angiosarcoma: a seer population based study. j am acad dermatol. 2019 jul 13. pii: s01909622(19)32382-5. 2. surveillance, epidemiology, and end results (seer) program (www.seer.cancer.gov) seer*stat database: incidence seer 18 regs research data + hurricane katrina impacted louisiana cases, nov 2018 sub (2000-2016) <katrina/rita population adjustment> linked to county attributes total u.s., 1969-2017 counties, national cancer institute, dccps, surveillance research program, released april 2019, based on the november 2018 submission. 3. huang nc, wann sr, chang ht, lin sl, wang js, guo hr. arsenic, vinyl chloride, viral hepatitis, and hepatic angiosarcoma: a hospital-based study and review of literature in taiwan. bmc gastroenterol. 2011;11:142. 4. ishida y, otsuka a, kabashima k. cutaneous angiosarcoma: update on biology and latest treatment. curr opin oncol. 2018;30(2):107–112. 5. painter ca, jain e, tomson bn, dunphy m, stoddard re, thomas bs, damon al, shah s, kim d, gómez tejeda zañudo j, hornick jl, chen yl, merriam p, raut cp, demetri gd, van tine ba, lander es, golub tr, wagle n. the angiosarcoma project: enabling genomic and clinical discoveries in a rare cancer through patient-partnered research. nat med. 2020 feb;26(2):181-187. conclusion skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 232 table 1. second primary malignancy occurrence following cutaneous angiosarcoma diagnosis by specific sites. observed expected o/e ci lower ci upper excess risk all sites 32 20.85 1.54* 1.05 2.17 107.02 oral cavity and pharynx 1 0.49 2.04 0.05 11.34 4.88 digestive system 3 4.36 0.69 0.14 2.01 -13.02 respiratory system 3 3.42 0.88 0.18 2.56 -4.03 bones and joints 0 0.02 0 0 191.08 -0.19 soft tissue including heart 4 0.13 30.58* 8.33 78.3 37.12 skin excluding basal and squamous 9 1.24 7.26* 3.32 13.78 74.45 melanoma of the skin 1 1.1 0.91 0.02 5.09 -0.91 other non-epithelial skin 8 0.14 55.28* 23.87 108.93 75.37 breast 2 1.4 1.43 0.17 5.16 5.75 female genital system 0 0.53 0 0 6.95 -5.1 male genital system 4 3.71 1.08 0.29 2.76 2.77 urinary system 2 2.39 0.84 0.1 3.02 -3.74 eye and orbit 0 0.03 0 0 109.1 -0.32 brain and other nervous system 0 0.2 0 0 18.04 -1.96 endocrine system 0 0.19 0 0 18.95 -1.87 all lymphatic and 2 2.05 0.98 0.12 3.53 -0.45 skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 233 hematopoietic diseases lymphoma 1 1.02 0.98 0.02 5.49 -0.15 myeloma 1 0.33 3.03 0.08 16.87 6.43 leukemia 0 0.7 0 0 5.26 -6.73 mesothelioma 0 0.09 0 0 43.33 -0.82 kaposi sarcoma 0 0.01 0 0 246.1 -0.14 miscellaneous 2 0.57 3.48 0.42 12.57 13.67 excess risk is per 10,000, confidence intervals are 95% * p < 0.05 powerpoint presentation the integrated 31-gene expression profile (i31-gep) test for cutaneous melanoma outperforms cp-gep at identifying patients who can safely forego sentinel lymph node biopsy. background methods › management of patients with melanoma involves multiple decision points during clinical care, all of which, in line with guidelines, should be aligned with a patient’s risk for poor outcomes. the 31-gene expression profile (gep) was developed and validated to predict a patient’s risk of recurrence and further validated to precisely predict a patient’s individualize risk for a positive slnb. › an slnb risk threshold weighs surgical risks against those of missing a positive sln. current guidelines recommend a 5% risk threshold for considering slnb in patients with cutaneous melanoma (t1a with highrisk features, t1a-hr-t4).1 › a 5% threshold indicates that, in a group of 20 similar patients foregoing slnb, 19 would have a negative slnb, with one missed positive sln (19:1 negative:positive ratio).2,3 any novel test to identify patients who can forego slnb should increase the ratio of negative-to-missed positive nodes (figure 1). › a second gep test was developed to identify patients at low risk of sln metastasis, cp-gep, but is not available for survival prognostication.11-12 acknowledgments & disclosures references › funding provided by castle biosciences. › aj and pp are on the speaker's bureau for castle biosciences. bm is an employee and stock and options holder at castle biosciences. results presented at the 2022 fall clinical dermatology conference. › standard of care suggests that at a 5% risk threshold, for every 20 patients not getting an slnb, one positive node will be missed (19:1 true-to-false negative). to be safe and clinically useful, any new test must do better. › i31-gep: 30:1 true-to-false negative slnb ratio is better than using standard of care for identifying patients who may safely forego slnb. › cp-gep: 15:1 true-to-false negative slnb ratio is worse than using standard of care. › the i31-gep is the only test to offer both slnb risk prediction and risk of recurrence, metastasis, or death prognostication. conclusions › we compared the performance of two gep tests, the i31-gep (n=763)4 and the cp-gep (u.s. validation cohort; n=153 [includes three t1a]),12 in patients with t1bt2 tumors, with known slnb results, to determine if either test increased the ratio of negative-to-missed positive nodes. scan or click here for more info figure 2. only the i31-gep performs better than standard of care at identifying those who can safely forgo slnb (t1b-t2) figure 1. current guidelines suggest considering slnb when the risk of a positive biopsy is ≥5% (t1ahr– t4) 1. national comprehensive cancer guidelines, v2, 2022. 2. vickers et al. bmj 2015. 3. vickers et al. diagn progn res. 2019. 4. whitman et al. jco po 2021. 5. vetto et al. future oncology. 2019. 6. hsueh et al. jco po 2021. 7. jarell et al. jaad. 2022. 8. arnot et al. ajs. 2021. 9. dillon et al. cmro.2022. 10. ahmed et al. cancer med. 2022. 11. bellomo et al. jco po 2020. 12. yousaf et al. ijd 2021. 13. mulder et al. bjd 2020. 19:1 15:130:1 i31-gep standard of care cp-gep missed positive slntrue negative sln (safely forego slnb) cp-gep would miss more positive nodes per 100 ‘low-risk’ patients (n~6; 100/15) than using the current standard of 5% (n=5), while i31-gep would miss less than the standard (n~3; 100/30) and half as much as cp-gep. 1 missed positive sln per 31 considered low-risk 1 missed positive sln per 20 not done 1 missed positive sln per 16 considered low-risk 31-gep: better than standard of care cp-gep: worse than standard of care clinical impact and objective • patient management decisions, including the decision to undergo slnb, should be risk-appropriate to the individual being considered for treatment. currently, national guidelines recommend patients consider slnb when risk reaches a 5% threshold, broadly identified by t-stage (t1a with high-risk features and greater). thus, by guidelines, an allowable threshold for true negatives to false negatives when foregoing slnb is 19:1, and any test use to guide this decision should be superior to this benchmark. • to compare the utility of the i31-gep and cp-gep for slnb guidance with the current standard of care in t1b-t2 cutaneous melanoma. i31-gep results adapted from whitman et al. jco po 2021.4 cp-gep results obtained from yousaf et al. ijd 2021.12 tn: true negative. fn: false negative. test tn fn ratio (tn:fn) i31-gep 154 5 30:1 (154/5) standard 19 1 19:1 (19/1) cp-gep 60 4 15:1 (60/4) abel jarell, md,1 brian martin, phd,2 peter prieto, md, mph3 1northeast dermatology associates, pc, portsmouth, nh, 2castle biosciences, inc., friendswood, tx, 3university of rochester medical center, rochester, ny https://castlebiosciences.com/research-development/publications/ powerpoint presentation results discussion a pilot study, to evaluate the safety and efficacy of topically applied onabotulinum toxin a delivered through a novel iontophoresis device in subjects with axillary hyperhidrosis mark s. nestor, m.d., ph.d.1,2, haowei han, d.o.1, anita gade, d.o.1, francesca ceci, m.d.1, alec lawson, b.a.1, austin dunn, d.o.1, faraz yousefian, d.o., 1 ciaran smythe, d.o.1 1center for clinical and cosmetic research, 2 department of dermatology and cutaneous surgery, university of miami miller school of medicine it is estimated that 4.8% of the united states population suffers from hyperhidrosis.1 onabotulinum toxin injections are fda approved for the treatment of hyperhidrosis, but many patients do not want injections due to pain or fear of needles.2 iontophoresis is fda approved for hyperhidrosis of the palms and works by sending electrical currents through the skin. in contrast with traditional iontophoresis, however, the novel iontophoresis device used in the present study uses low-intensity pulsed currents and has different electrode configurations developed to enhance the absorption of substances into the skin. early studies have demonstrated its potential to deliver topical onabotulinum toxin to treat hyperhidrosis. this pilot study aims to evaluate the safety and efficacy of transdermal delivery of botulinum toxin delivered through the novel iontophoresis device for primary axillary hyperhidrosis. methods subjects: 5 healthy subjects with documented hyperhidrosis (gravimetric >50 mg) study design: baseline gravimetric sweat measurements and starch iodine tests, were assessed before study treatment. topical onabotulinum (50 u per axilla) was delivered via the transdermal infusiontm novel iontophoresis device (sensus healthcare, boca raton fl). follow-up measurements were taken 7, 14, and 28 days after treatment. for the first subject, the botulinum toxin was combined with double the amount of suspension used in the other subjects. it was noted that there was too much solution to be completely absorbed by the treatment area. consequently, the methods were changed for the following subjects so that a fraction of the amount of suspension was used, creating a higher concentration of botulinum toxin. previous clinical trials have demonstrated the efficacy of onabotulinum toxin injections for the treatment of hyperhidrosis. 91% (219/242) had at least a 50% reduction from baseline in axillary sweating 4 weeks post-injection of 50 units per axilla (mean reduction = 83.4% with a sd = 21.6). 3 the present study demonstrated similar results with the use of onabotulinum toxin delivered topically, without the use of needles. the lack of response to treatment in subject 1 who acted as control, was due to excessive gel which was not absorbed in the skin. for the subsequent subjects we utilized a fraction of the volume of normal saline which was completely absorbed in the skin. subject 1 serves as a control to support the claim that the treatment success in the other subjects was due to the successful delivery of the topically applied botulinum toxin, and not due to the effects of iontophoresis alone. the subjects included 2 males and 3 females (age range: 19-47 years) with symptoms of hyperhidrosis for a mean of 9 years. subject #1 acted as a control because of the excessive diluent. all other subjects demonstrated improved symptoms of hyperhidrosis, quantified by the gravimetric sweat tests (figure 1). figure 2 shows an example of the starch iodine test. overall, the procedure was well tolerated by all patients. one patient reported muscle fasciculations of the left shoulder and chest for 2 days without pain or discomfort. no other adverse events were noted. conclusion this pilot study appears to demonstrate that after one treatment with the transdermal infusiontm novel iontophoresis device and topically applied onabotulinum toxin at injectable approved dose (50u per axilla), subjects had dramatically reduced axillary hyperhidrosis. the results suggest that this treatment is safe and efficacious for axillary hyperhidrosis. we anticipate a future, larger study, to determine this treatment's clinical significance. references 1. doolittle, j., walker, p., mills, t. & thurston, j. hyperhidrosis: an update on prevalence and severity in the united states. arch. dermatol. res. 308, 743–749 (2016). 2. mclenon, j. & rogers, m. a. m. the fear of needles: a systematic review and meta-analysis. j. adv. nurs. 75, 30–42 (2019). 3. naumann, m. & lowe, n. j. botulinum toxin type a in treatment of bilateral primary axillary hyperhidrosis: randomised, parallel group, double blind, placebo controlled trial. bmj 323, 596 (2001). figure 1. gravimetric sweat measurements relative to baseline screening/baseline 7-days post 14 days post 28 days post subject 1 0% -30% 11% -7% subject 2 0% -54% -37% -81% subject 5 0% -69% -72% -70% subject 6 0% -67% -60% -81% subject 7 0% -9% -52% -60% 0% -30% 11% -7% 0% -54% -37% -81% 0% -69% -72% -70% 0% -67% -60% -81% 0% -9% -52% -60% -100% -80% -60% -40% -20% 0% 20% gravimetric sweat measurements relative to baseline baseline 243.7 mg day 28 76.3 mggravimetric tests: figure 1. starch iodine test at baseline (pre-treatment) and at day 28 introduction https://paperpile.com/c/nrmhfn/0vqng https://paperpile.com/c/nrmhfn/ebfon https://paperpile.com/c/nrmhfn/iijt slide number 1 skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 723 brief article perioral contact dermatitis caused by limonene hydroperoxide in cannabis vaping products kevin mai1, quang d. pham1, joseph haquang1, diem q. pham, do1,2 1 college of osteopathic medicine of the pacific, western university of health sciences, pomona, california 2 sand dermatology, chino hills, ca limonene is a fragrant hydrocarbon monoterpene compound naturally found in plants, spices, and citrus oils.1 due to its desirable aromatic qualities, it is one of the most common chemical additives in household products including cosmetics, essential oils, and cleaning supplies.1 the non-oxidized form of limonene can cause a weak fragrance allergy.2 when exposed to air, however, limonene rapidly autoxidizes and generates limonene hydroperoxide, a more potent contact sensitizer that has been noted to cause allergic contact dermatitis (acd).2,3 limonene’s availability and popularity has extended its use to novel products that use aerosolization such as electronic cigarettes or vapes.4 specifically, limonene is used as a flavoring agent within vaping liquid. the incorporation of limonene into these devices may lead to new presentations of limonene hydroperoxide allergic contact dermatitis. previous literature describes how limonene can cause a strong hypersensitivity reaction in individuals and may be more prevalent in those who work with limonene containing cosmetics. the description of how this may specifically present has been extremely limited.5 here, we report a case of an allergic contact dermatitis reaction to limonene hydroperoxide from cannabis vaping products presenting as a perioral rash. to the best of our knowledge, a case of contact dermatitis arising from limonene hydroperoxide found in cannabis vaping products has yet to be reported. a 31-year-old female presents for a worsening pruritic perioral rash that has been abstract limonene is a fragrant terpene commonly found in household and cosmetic products due to its fresh aroma. when exposed to air, limonene autoxidizes to form limonene hydroperoxide, a potent allergen that can cause allergic contact dermatitis. recently, as the popularity and availability of limonene increased, it has been incorporated into novel products such as flavoring agents for electronic cigarettes or vapes. with the rising acceptance and popularity of marijuana, this usage has extended to cannabis vaping products. here, we report an unusual presentation of an allergic contact dermatitis reaction to limonene hydroperoxide stemming from cannabis vaping products. introduction case report skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 724 present for one and a half years. she reports a significant history of acne, chronic back pain, scoliosis and an allergy to morphine. her medications include buspirone, cannabidiol, gabapentin, propranolol, prozac, trazodone, xanax and omeprazole. physical examination demonstrated angular cheilitis and dry lips at the periphery with fissures and erythema involving the bilateral superior cutaneous lip and apical triangles (figure 1). a serum vitamin, nicotinamide and zinc panel were ordered to rule out any vitamin deficiencies. zinc, nicotinamide and vitamin b1, b2, b3, b9 and b12 levels were unremarkable. a trial of topical 2% ketoconazole cream and topical 0.05% desonide ointment were ordered. figure 1. angular cheilitis and dry lips at the periphery with fissures and erythema involving the bilateral superior cutaneous lip and apical triangles. three months later, the patient returns with continual recurrence of her perioral rash. a patch test was conducted using the north american 80 comprehensive series. results from the first reaction were strongly positive for hydroperoxides of limonene and weakly positive for propolis, textile dye mix, disperse blue mix 106/124 and disperse orange 3 (figure 2, left). results from the second reaction were strongly positive for disperse blue mix 106/124 and weakly positive for limonene hydroperoxides, textile dye mix, glutaral, cobalt (ii) chloride hexahydrate and p-phenylenediamine (figure 2, right). upon further questioning she mentions that she has been consuming marijuana every two to three days for her chronic back pain through a vaping device. the patient was then prescribed a three-week course of fluconazole and a four-week trial of alclomethasone cream and informed to utilize a barrier for her lips when using the vape or to avoid using her marijuana vape altogether. a consequent follow-up showed continuation of the symptoms as the patient mentioned she was unable to taper down her use of the cannabis vape and that it continued to contact her lips. a crisaborole ointment was ordered instead for an expected long-term usage. crisaborole proved to be effective in controlling the perioral rash from june 2022 to december 2022. afterwards, our patient reported it was no longer effective. the patient was instructed to return for a follow up visit for a trial of ruxolitinib cream thereafter. as of now, the patient has not yet scheduled a follow up appointment. figure 2. patch testing with the north american 80 comprehensive series. acd is an inflammatory disorder of the skin resulting from an immune-mediated delayed hypersensitivity reaction.6 the nature of this discussion skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 725 condition is dependent on the sensitization of tcells following initial contacts with an allergen.6 the prevalence of acd is rising globally with an estimated 20% of the general population affected.7 patch testing has demonstrated that the frequency of limonene hydroperoxide sensitization ranges from an estimated 2.5% to 9.4%.8 this frequency is expected to increase with the coming years possibly due to the increasing popularity and availability of limonene. the clinical presentation of the patient’s angular cheilitis like rash and dry lips are nonspecific findings, overlapping with many other common pathologies such as candida perleche or vitamin deficiencies.9 hence, an unremarkable serum vitamin panel and persistence of the rash despite topical and oral antifungals helped rule out these differential diagnoses. additionally, her history of cannabis vaping, a positive patch testing for limonene and no other contributory factors, makes limonene hydroperoxide acd the likely culprit behind the lesions. the similarity in presentation between various diseases can hinder the diagnosis, delay removal of allergen exposure, and treatment of limonene triggered acd. therefore, to aid in differentiation between limonene triggered acd versus other pathologies, we highlight a unique location of the rash. specifically, our patient’s rash had a distinct predominance to the superior aspect of the lip and the apical triangles rather than simply adjacent to the mouth. because the rash stems from cannabis vaping, its location is likely caused by inhalation and expulsion of aerosolized limonene through the nostrils.3 overall, awareness of this possible presentation, obtaining a detailed history of allergen exposure, and examining the rash’s location can aid in diagnosing limonene hydroperoxide acd from cannabis vaping products. due to varied allergen exposure based on a patient's unique environment, acd's presentation and epidemiology can differ between patients and geographic locations.10 differences in environmental allergen exposure may be explained by cultural or policy changes such as marijuana’s legalization in several us states and worldwide. globally, the incidence of e-cig usage is rising. this phenomenon is likely due to the increasing legalization, social acceptance, and usage of recreational marijuana and electronic cigarettes in youths. many teenagers and adults are also drawn to electronic vapes due to the novelty and allure of trying different flavored solutions, causing increased exposure to limonene.11 in summary, we have presented an uncommon and previously unreported case of limonene hydroperoxide-associated acd from cannabis vaping. improved patient education involving both the adverse respiratory effects of e-cigarettes and cutaneous reactions could be instrumental in reducing limonene hydroperoxide-triggered acd. conflict of interest disclosures: none funding: none corresponding author: kevin mai college of osteopathic medicine of the pacific western university of health sciences 309 e 2nd st. pomona, ca 91766 email: kevin.mai@westernu.edu references: 1. anandakumar p, kamaraj s, vanitha mk. dlimonene: a multifunctional compound with potent therapeutic effects. j food biochem. jan 2021;45(1):e13566. doi:10.1111/jfbc.13566 conclusion skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 726 2. christensson jb, johansson s, hagvall l, jonsson c, borje a, karlberg at. limonene hydroperoxide analogues differ in allergenic activity. contact dermatitis. dec 2008;59(6):344-52. doi:10.1111/j.16000536.2008.01442.x 3. de groot a. limonene hydroperoxides. dermatitis. nov/dec 2019;30(6):331-335. doi:10.1097/der.0000000000000465 4. bitzer zt, goel r, reilly sm, et al. effect of flavoring chemicals on free radical formation in electronic cigarette aerosols. free radic biol med. may 20 2018;120:72-79. doi:10.1016/j.freeradbiomed.2018.03.020 5. pesonen m, suomela s, kuuliala o, henrikseckerman ml, aalto-korte k. occupational contact dermatitis caused by d-limonene. contact dermatitis. nov 2014;71(5):273-9. doi:10.1111/cod.12287 6. mowad cm, anderson b, scheinman p, pootongkam s, nedorost s, brod b. allergic contact dermatitis: patient diagnosis and evaluation. j am acad dermatol. jun 2016;74(6):1029-40. doi:10.1016/j.jaad.2015.02.1139 7. peiser m, tralau t, heidler j, et al. allergic contact dermatitis: epidemiology, molecular mechanisms, in vitro methods and regulatory aspects. current knowledge assembled at an international workshop at bfr, germany. cell mol life sci. mar 2012;69(5):763-81. doi:10.1007/s00018-011-0846-8 8. dittmar d, schuttelaar mla. contact sensitization to hydroperoxides of limonene and linalool: results of consecutive patch testing and clinical relevance. contact dermatitis. feb 2019;80(2):101-109. doi:10.1111/cod.13137 9. federico jr, basehore bm, zito pm. angular chelitis. statpearls. 2022. 10. cappelli l, poiset s, greenberger b, bar-ad v. thermoplastic mask-induced contact dermatitis: a case report. cureus. apr 2022;14(4):e23815. doi:10.7759/cureus.23815 11. jones k, salzman ga. the vaping epidemic in adolescents. mo med. jan-feb 2020;117(1):56-58. skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 581 research letter financial burden of parking fees for phototherapy patients: a cross-sectional study kyaw zin htet, ba1, theresa bui, bs1, apurv srivastav, ms2, andrea murina, md3, drew kuraitis, md, phd3,4 1tulane university school of medicine, new orleans, la 2division of biostatistics, university of california, davis, ca 3department of dermatology, tulane university school of medicine, new orleans, la 4department of dermatology, roswell park comprehensive cancer center, buffalo, ny narrow band uvb phototherapy is a common treatment for many dermatologic conditions. although, it is often covered by insurance or by safety net hospitals, there may still be significant treatment-associated parking costs as patients frequently require multiple sessions per week at a designated clinical site. parking fees for cancer patients can approach thousands of dollars annually, posing a barrier for financially disadvantaged patients.1 this cross-sectional study aimed to assess parking fees associated with phototherapy across the united states and to investigate geographic associations with cost of living and transit access. clinical sites were identified as those affiliated with u.s academic dermatology residency programs. the following information for each site was ascertained via phone calls and online search, if available: phototherapy center address, transit score, city cost of living score, public transit information, parking rates and reimbursement for phototherapy patients (supplemental methodology available at https://data.mendeley.com/datasets/376wv4 4c9b/1). mean, median, and range of each score and cost were calculated, and a spearman correlation was calculated for two variables. of 343 identified clinical sites, 314 responded while 29 did not respond. of the 314 participant sites, 69 sites did not offer phototherapy services, and 6 sites did not have on-site parking. full information (parking costs, city cost of living and transit score) was only available for 177 sites (table 1). of the sites with full available information, 124 (124/177; 70.1%) offered free or validated parking for all patients, and 65 (65/177; 36.7%) have public transportation information available on their website. hourly parking costs were associated with transit score (fig. 1a; r= 0.241, p=.0004) and city cost of living (fig. 1b; r=0.207, p=0.006). parking fees represent significant nonmedical financial barrier to patients undergoing phototherapy treatment, especially if multiple times per week. in our study, 8.5% (29/343) of phototherapy sites did not detail parking fees on their websites nor provide such information via telephone inquiry. this can lead to unexpected financial costs related to medical treatment which in turn could lower patients’ willingness to pay for care.2 we also found that cities with a https://data.mendeley.com/datasets/376wv44c9b/1 https://data.mendeley.com/datasets/376wv44c9b/1 skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 582 table 1. transit score, transit score correlations with/without free parking and with/without public transportation information online, city cost of living score, city cost of living score correlations with/without free parking and with/without public transportation information online and, parking costs. abbreviation: iqr = interquartile range. a the transit score range is from 0-10, with 0-3 indicating minimal transit options and 8-10 indicating efficient and accessible transportation. b the city cost of living was indexed to 100, with 100 being the average cost of living and index values above 100 indicate that the city has a cost living above the average, while values below 100 indicate a cost of living below the average. cthe n value represents the clinical sites with full information available for analysis (parking costs, city cost of living and transit score) dthe n value represents the clinical sites that charges parking fees for patients variable n mean  sd median (iqr) range, lowhigh t test (p value) phototherapy center address transit scorea 177c 7.99  2.05 8.50 (7.10 9.60) 0.00 – 10.00 phototherapy center address transit score in sites with free parking 132 7.77  2.13 8.30(7.10 – 9.30) 0.00 – 10.00 0.0004 phototherapy center address transit score in sites without free parking 45 8.61  1.69 9.50 (8.20 – 9.70) 1.50 – 10.00 phototherapy center address transit score with public transportation information online 112 7.66  2.04 8.20(7.00 – 9.20) 0.00 – 9.90 0.0049 phototherapy center address transit score without public transportation information online 65 8.55  1.97 7.30 (8.30 – 9.70) 1.50 – 10 city cost of living score 177c 108.1  19.19 102.00 (93.70 118.70) 87.30 – 183.00 city cost of living score in sites without free parking 132 106.0  17.71 100.30 (93.50 – 110.5) 87.30 – 183.00 0.0057 city cost of living score in sites with free parking 45 114.3  22.06 105.30 (96.9 – 128.0) 88.20 – 183.00 city cost of living score in sites without public transportation information online 112 104.9  16.53 100.25 (93.42 – 108.20) 90.07 – 183.00 0.0033 city cost of living score in sites with public transportation information online 65 113.6  22.13 105.3 (95.8– 128.0) 87.30 – 181.10 cost of parking, $ hour 53d 5.10  5.55 4.00 (2.00 – 5.00) 0.00 – 26.00 day 53d 12.7  9.22 10.0 (6.0 – 15.0) 0.00 – 44.00 skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 583 figure 1a & b. pearson correlations between transit score and city cost of living with hourly parking costs. each plotted dot represents a medical center that offer phototherapy services. abbreviation: d = day. hourly parking costs were associated with transit scores (fig 1a; r= 0.241, p=.0004) and cost of living (fig 1b; r=0.207, p=0.006). skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 584 higher cost of living do not have as much free parking, compounding financial barriers. the average median parking cost in our study was $5.10, amounting to $798.15 annually for thrice weekly therapy. home phototherapy units range from $900 to $1500 and can be more cost-effective given similar clinical efficacy to office-based phototherapy and elimination of non-medical costs such as parking fees.3,4 as inconvenience and therapy-associated costs are lead reasons for patient discontinuation of phototherapy, home unit provision should be pursued in an effort to reduce long-term costs and improve patient adherence.5 for patients requiring inoffice phototherapy, clinical sites should offer validated or free parking to eliminate nonmedical financial barriers. study limitations include limited number of sites that were available for data collection, as those that could not be reached through website and/or telephone as well as those without full information from data sources were not included in the study. our study sample was limited to academic/teaching centers and thus may not be representative of all sites offering phototherapy. there could also be inaccuracy of costs that were collected through website and/or telephone, as websites and site staff may not have updated information available. phototherapy remains a first-line treatment modality for various dermatological conditions, given its great efficacy, high tolerability and low cost profile. with an increase usage of phototherapy services among medicare and medicaid beneficiaries, it is important for clinicians to be aware of non-medical costs such as parking fees that could further contribute to the health disparities of the population.6 conflict of interest disclosures: none funding: none corresponding author: drew kuraitis, md, phd 1430 tulane avenue #8036 phone: (504) 988-5114 email: dkuraiti@tulane.edu references: 1. lee a, shah k, chino f. assessment of parking fees at national cancer institutedesignated cancer treatment centers. jama oncol. aug 1 2020;6(8):1295-1297. doi:10.1001/jamaoncol.2020.1475 2. chino f, peppercorn jm, rushing c, et al. out-of-pocket costs, financial distress, and underinsurance in cancer care. jama oncol. nov 1 2017;3(11):1582-1584. doi:10.1001/jamaoncol.2017.2148 3. jacob j, pona a, cline a, feldman s. home uv phototherapy. dermatol clin. jan 2020;38(1):109-126. doi:10.1016/j.det.2019.09.001 4. lim hw, silpa-archa n, amadi u, menter a, van voorhees as, lebwohl m. phototherapy in dermatology: a call for action. j am acad dermatol. jun 2015;72(6):1078-80. doi:10.1016/j.jaad.2015.03.017 5. yentzer ba, feldman sr. trends in home phototherapy adoption in the us: monetary disincentives are only the tip of the iceberg. j dermatolog treat. feb 2011;22(1):27-30. doi:10.3109/09546630903440080 6. tan sy, buzney e, mostaghimi a. trends in phototherapy utilization among medicare beneficiaries in the united states, 2000 to 2015. j am acad dermatol. oct 2018;79(4):672-679. doi:10.1016/j.jaad.2018.03.018 skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 159 brief articles generalized lichen nitidus in a middle-aged adult matthew lacour md1, julie croley md2, janice wilson md2 1school of medicine, university of texas medical branch, galveston, tx 2department of dermatology, university of texas medical branch, galveston, tx lichen nitidus (ln) is a benign micropapular eruption of unknown etiology that often follows an unpredictable course. ln typically affects children and young adults and presents with asymptomatic, discrete, uniform, skin colored, pin-point sized papules.1 these papules are commonly found on the chest, abdomen, flexor surfaces of the upper extremities, dorsal hands, and anogenital region.1 focal presentation is more common, while generalized distribution of ln is rarer and seen almost exclusively in pediatric patients.2 patients are typically asymptomatic, though pruritus can occur.1 an uncommon case of generalized ln is reported in a middle-aged adult emphasizing an approach to diagnosis and treatment. in the majority of affected patients, ln is associated with spontaneous resolution after a few months to years, but clinical course of the generalized form is unpredictable.3 generalized cases are infrequently noted, with the majority of reported cases affecting children.4 due to the rarity of presentation of generalized ln in adults, skin biopsies were essential in confirming the diagnosis. biopsies characteristically show a lymphocytic infiltrate with downward extension of lateral rete ridges forming a typical “ball-and-claw” formation.1 it is not necessary to treat localized presentations of lichen nitidus as they typically resolve over a month to a year.4 patient and provider chose to treat this diffuse, worsening generalized. treatment introduction lichen nitidus (ln) is a benign micropapular eruption of unknown etiology that often follows an unpredictable course. ln typically affects children and young adults and presents with asymptomatic, discrete, uniform, skin colored, pin-point sized papules.1 these papules are commonly found on the chest, abdomen, flexor surfaces of the upper extremities, dorsal hand, and anogenital region.1 focal presentation is more common while generalized distribution of ln is rarer and seen more exclusively in pediatric patients.2 although patients are typically asymptomatic, pruritus is sometimes a noted symptom.1 we report the diagnosis and treatment of an uncommon case of generalized ln in a middle-aged adult. discussion abstract skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 160 can also provide relief of pruritus. treatment options include oral antihistamines, systemic or topical steroids, acitretin, psoralen ultraviolet a (puva), narrow-band ultraviolet b (nb-uvb) and dinitrochlorobenzene.2,3 although it is difficult to evaluate the effectiveness of treatment in a rare disease with a propensity to spontaneously resolve, phototherapy may be the most beneficial treatment for generalized ln with the least potential for side effects.4 broadband uvb and puva have greater carcinogenic potential. nb-uvb is, therefore, preferred. it is thought to deplete langerhans cells and promote the production of anti-inflammatory factors.3 nb-uvb was elected for this patient but her insurance would not cover the treatment. the patient was lost to follow up, but she stated in follow up emails that she had some resolution of ln. the unusual features of older patient age, generalized distribution, and marked pruritus in the setting of comorbid primary biliary cirrhosis makes this case of ln particularly unique. it is important for dermatologists to recognize the variable presentations of uncommon cutaneous diseases like generalized ln and the need for biopsy in establishing a definitive diagnosis. figure 1. skin findings show diffuse, fine, 1-2 mm sized innumerable flesh colored papule on the back and face. figure 2. punch biopsy demonstrates a focal lymphohistiocytic lichenoid infiltrate and epidermal acanthosis or "ball and claw" configuration. (hematoxylin-eosin stain) conflict of interest disclosures: none funding: none corresponding author: matthew lacour, md 1202 church st galveston, texas 77550 phone: 281-798-5667 email: mdlacour@utmb.edu references: 1. arizaga, a. t., gaughan, m. d. and bang, r. h. (2002), generalized lichen nitidus. clinical and experimental dermatology, 27: 115-117. 2. al‐mutairi, n. , hassanein, a. , nour‐eldin, o. and arun, j. (2005), generalized lichen nitidus. pediatric dermatology, 22: 158-160. 3. do mo, kim mj, kim sh, et al. generalized lichen nitidus successfully treated with narrowband uvb phototherapy: two cases report. j korean med sci. 2007;22:163–6. 4. synakiewicz j, polańska a, bowszycdmochowska m, et al. generalized lichen nitidus: a case report and review of the literature. advances in dermatology and allergology/postȩpy dermatologii i alergologii. 2016;33(6):488-490. doi:10.5114/ada.2016.63890. mailto:mdlacour@utmb.edu skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 844 brief article blastomycosis-like pyoderma in a 59-year-old male with type 2 diabetes mellitus michela salusti-simpson, ba1, hannah porter, md, mba, ms1, dustin taylor, md2, evan piette, md1 1university of vermont medical center, burlington, vt 2brigham and women’s hospital, boston, ma blastomycosis-like pyoderma (blp) is a rare cutaneous disorder that results from an exaggerated response to a bacterial infection, most commonly staphylococcus aureus. there are a variety of reported predisposing factors, including diabetes, obesity, leukemia, primary immunodeficiency, and active immunomodulatory therapy.1 clinical and histopathological findings of blp can be quite disparate, often resulting in a delay in diagnosis.2 we report here a case of a man who presented with an enlarging verrucous nodule of his neck, and was subsequently diagnosed with blp. the purpose of sharing this case is to contribute to the existing literature of this rare disease by highlighting a unique presentation. a 59-year-old congolese male with a past medical history of type 2 diabetes mellitus and latent syphilis presented to the dermatology clinic with a one-month history of a tender, draining mass on his right neck. he had never had anything like this before, and denied any associated numbness, itching, or bleeding. he denied recent travel and new exposures but had moved to the us from kenya through a refugee settlement program in 2017. he was feeling well otherwise. he denied any history of other cutaneous conditions. on exam, there was a firm, hyperpigmented papillomatous nodule with central ulceration on the right lateral neck and upper back (figure 1). extending up the right posterior neck into the scalp, there were several similar, smaller firm nodules (figure 2). initial differential diagnosis included malignancy (in particular, squamous cell carcinoma vs lymphoma) vs. infection (deep fungal, atypical mycobacterium, sporotrichosis, and leishmaniasis, amongst others). the patient had visited an outside primary care office one week earlier, where a punch biopsy with hematoxylin and eosin (h&e) stain was done. this initial biopsy revealed nonspecific reactive epidermal hyperplasia with mixed dermal inflammatory infiltrate. the patient shortly thereafter returned to the dermatology office for an excisional biopsy, which yielded pseudoepitheliomatous hyperplasia with dermal abscess formation (figure 3). afb and fungal culture were negative for organisms, but the bacterial culture did return introduction case report skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 845 positive for methicillin-resistant staph aureus (mrsa). one week after the excisional biopsy, the patient was reporting increased pain and purulent drainage of the primary lesion. the patient was started on doxycycline 100mg twice daily for 10 days, and he noted slight decrease in pain and drainage. figure 1. firm, hyperpigmented papillomatous nodule with central ulceration on the right lateral neck and upper back. as the lesion was continuing to grow, additional workup including histoplasmosis urine antigen and serum antibody, hiv serology, blastomycosis urine antigen, and quantiferon gold were obtained. given the patient’s known history of latent syphilis, an rpr was obtained to monitor for recurrence. all of these tests returned negative. the differential diagnosis was further expanded to include pemphigus vegetans, halogenoderma, and blastomycosis-like pyoderma. to explore this further, a third biopsy was pursued, along with h&e, direct immunofluorescence (dif), repeat tissue culture, and universal pathogen polymerase chain reaction (pcr). punch biopsy specimens revealed reactive epidermal hyperplasia with dermal fibrosis and lymphoplasmacytic infiltrate, and dif was negative. tissue cultures were significant for proteus mirabilis. universal pcr returned negative for all clinically concerning organisms, including atypical mycobacterium, toxoplasma, and fungal species. figure 2. smaller nodule extending up the right posterior neck into the scalp. given these results and the patient’s clinical presentation, the working diagnosis was blp. the patient was placed on an additional 3-month course of doxycycline 100 mg twice daily and experienced rapid healing of the lesion. with the patient’s remarkable skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 846 response to a course of doxycycline, it was presumed that the likely provoking factor for his blp was mrsa. the patient has continued to do well since, without any recurrence. figure 3. excisional biopsy which yielded pseudoepitheliomatous hyperplasia with dermal abscess formation. blp is a rare cutaneous disease characterized by an exuberant response to a bacterial infection, most commonly staphylococcus aureus. other reported etiologies have included streptococcus pyogenes, pseudomonas aeruginosa, escherichia coli, and candida albicans. the mechanism by which these pathogens lead to the development of blp is not known, but it has been hypothesized that the microorganisms induce local immune dysfunction.3 blp classically presents in immunocompromised individuals, but has been reported after tattooing, local trauma, radiotherapy, and foreign body reactions in immunocompetent hosts.3,4 sahli et al., published a case report in 2022 of blp of the left wrist in an immunocompetent female patient with type 2 diabetes mellitus.3 similarly, our patient also had a history of type 2 diabetes mellitus, but was otherwise immunocompetent. the classic exam findings for blp are large verrucous plaques with multiple pustules, elevated borders and draining sinuses, often on sun-exposed areas.2 however, a case series of 39 patients with a history of blp highlighted the overall wide variety of potential findings, including plaques (with or without sinuses and crypts), solitary nodules, or ulcers.2 only three patients of the 39 presented with multiple lesions. representative histopathology can be just as diverse, but most commonly reveals pseudoepitheliomatous hyperplasia and abscess formation. scuderi et al. reported findings of chronic granulomatous inflammation, transepidermal elimination and scarring, and focal suppuration as well.2 understandably, this array of nonspecific features often leads to delayed diagnosis. directed antibiotics have been the mainstay of treatment for blp, although many patients do not experience full resolution. recent reports have emphasized the use of acitretin to treat blp. a patient with blp of her left palm in association with recurrent vesicular hand eczema had full resolution of her blp on oral acitretin 25 mg daily for ten weeks. other reported efficacious treatments include combined antibiotic and acitretin therapy, topical antibiotics, steroids, surgery, curettage and electrodessication, and laser therapy.5 our case represents another unique presentation of blp, as it highlights this diagnosis in an overall immunocompetent individual and the process of detecting blp through a broadened differential after initial discussion conclusion skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 847 testing. in addition, besides a history of diabetes mellitus, this patient did not present with any other known risk factors for blp including: trauma to skin, malnutrition, tattooing activity, smoking, cancer, or alcoholism.6 there can be great difficulty in making a diagnosis of blp and it is important to consider this diagnosis when a patient presents with a verrucous lesion mimicking blastomycosis. we are hopeful this case is helpful in expanding the differential diagnosis of clinicians faced with similar findings in patients with or without risk factors. consent: the patient gave consent for their medical information to be published in print and online and with the understanding that this information may be publicly available. conflict of interest disclosures: none funding: none corresponding author: michela salusti-simpson university of vermont medical center 111 colchester avenue burlington, vermont 05401 email: michela.salusti-simpson@med.uvm.edu references: 1. hongal aa, gejje s. blastomycosis-like pyodermaa rare case report. j clin diagn res. 2016;10(10):wd03-wd04. doi:10.7860/jcdr/2016/20468.8610 2. scuderi s, o'brien b, robertson i, weedon d. heterogeneity of blastomycosis-like pyoderma: a selection of cases from the last 35 years. australas j dermatol. 2017;58(2):139-141. doi:10.1111/ajd.12446 3. sahli f, litaiem n, gara s, charfi o, rammeh s, zeglaoui f. blastomycosis-like pyoderma in an immunocompetent patient. clin case rep. 2022;10(2):e05479. published 2022 feb 25. doi:10.1002/ccr3.5479 4. guidry ja, downing c, tyring sk. deep fungal infections, blastomycosis-like pyoderma, and granulomatous sexually transmitted infections. dermatol clin. 2015;33(3):595-607. doi:10.1016/j.det.2015.03.019 5. cecchi r, bartoli l, brunetti l, pavesi m. blastomycosis-like pyoderma in association with recurrent vesicular hand eczema: good response to acitretin. dermatol online j. 2011;17(3):9. published 2011 mar 15. 6. ilagan fmd, wu yh. blastomycosis-like pyoderma: a pitfall for the misdiagnosis of squamous cell carcinoma. j cutan pathol. 2022;49(12):1035-1039. doi:10.1111/cup.14298 skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 165 brief articles hyperpigmentation associated with the use of topical cidofovir for treatment of trichodysplasia spinulosa in an immunosuppressed adult: case report and review of the literature roya s. nazarian ba1, nikki s vyas md2, john evans md3, robert g. phelps md2,3 1icahn school of medicine at mount sinai, new york, ny 2department of dermatology, icahn school of medicine at mount sinai, new york, ny 3department of pathology, icahn school of medicine at mount sinai, new york, ny trichodysplasia spinulosa (ts) is a rare, infectious skin disease seen in severely immunocompromised hosts.1 this unusual disease is caused by infection with the polyoma virus, a small dna virus in the polyomaviridae virus family. multiple treatments exist including oral acitretin, valganciclovir, lefludomide, topical cidofovir, physical extraction, and modification of immunosuppressive medications. clinically, ts is characterized by follicular papules, keratin spicules, and alopecia most classically in a midfacial distribution.2 since its discovery in 2010, no standard of treatment has been established. proper diagnosis and treatment is crucial to prevent painful and potentially disfiguring lesions. we report the case of a 52-year-old african american female with a one-year history of a painful eruption on her face. her past medical history was significant for renal transplant from an unknown childhood illness, hiv infection controlled with highly active antiretroviral therapy (haart), hypertension, thyroid nodules, and uterine case report introduction trichodysplasia spinulosa (ts) is a rare, opportunistic infectious skin disease caused by the polyoma virus. clinically, ts is characterized by follicular papules, keratin spicules, and alopecia most classically in a midfacial distribution. since its discovery in 2010, no standard of treatment has been established, though use of oral acitretin, valganciclovir, lefludomide, topical cidofovir, physical extraction, and modification of immunosuppressive medications have been reported in the literature. we describe the case of a 52-year old female with a painful midfacial eruption and alopecia of the bilateral eyebrows ultimately diagnosed with ts and treated with topical cidofovir 3%. though the ts eruption resolved, treatment resulted in hyperpigmentation of the affected area. hyperpigmentation associated with cidofovir use has been reported in cases of molluscum contagiosum, however no such association has been described in the treatment of ts to our knowledge. therefore, we report this case to highlight an underreported adverse effect of topical cidofovir in the setting of this rare disease. abstract skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 166 fibroids. her medications included betalacept (5mg/kg iv every 4 weeks), tacrolimus (1 mg daily), prednisone (5mg daily), oxybutynin (15mg daily), gabapentin (300mg daily), dolutegravir (50mg daily), and emtricitabine-tenofovir (200-25mg daily). laboratory findings were notable for a white blood cell count of 3,200 (4,000-11,000), hemoglobin of 10.5 (12-15.5), hematocrit of 32.9 (36.1-44.3), platelets of 195 (150-450), bun of 27 (10-15), creatinine of 1.79 (0.61.1mg), calcium of 10.6 (8.5-10.5mg/dl), ldl of 107 (100-120 mg/dl), and total cholesterol of 239 (<200mg/dl). all other laboratory values were normal. physical exam was significant for multiple skin colored, erythematous, firm papules, with spicules on the mid-face. concomitant eyebrow alopecia was also appreciated. the patient endorsed occasional pain but no pruritus, burning or other symptoms. the differential diagnosis included acne vulgaris, trichodysplasia spinulosa, lichen spinulosus, trichoepitheliomas, colloid milium, and milia. she was treated for presumed acne vulgaris with salicyclic acid chemical peels, adalapene gel, benzoyl peroxide wash, and ultimately oral isotretinoin; however this resulted in no significant improvement. a curettage biopsy subsequently demonstrated dilated, distended hair follicles within the dermis, without obvious shaft formation (figure 1). the hair shaft was effaced and lacked true hair formation. follicles were filled with abnormal, dense keratinization and excessive inner root sheath production. no outer root sheath or hair bulb papillae were present (figures 2 and 3). the constellation of findings was most consistent with a diagnosis of trichodysplasia spinulosa. the patient was treated with once daily compounded topical cidofovir 3% cream (with versabase® cream). after 8 months of therapy, the facial eruption completely resolved, however residual hyperpigmentation of the affected area was noted at the one-year follow-up. ingredients of the cream base were reviewed with the compounding pharmacy and included the common contact allergens methylchloroisothiazolinone, methylisothiazolinone, ethylhexyl stearate, cyclopentasiloxane, sorbitol, aloe barbadensis leaf juice, tocopheryl acetate, and disodium edta. figure 1. erythematous follicular papules and spicules of the mid-central face associated with alopecia of the eyebrows were appreciated on examination. skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 167 in order to rule out contact dermatitis, the patient underwent patch testing with the topical cidofovir cream and specifically methylchloroisothiazolinone and methylisothiazolinone. however, the results were negative for hypersensitivity. the patient discontinued topical cidofovir cream, which resulted in mild improvement of hyperpigmentation but recurring ts lesions. she chose to resume topical cidofovir, and the hyperpigmentation persists at the16month follow-up. figure 2a. a curettage biopsy shows a disrupted, dilated, distended hair follicle within the dermis (h&e, 100x). no hair shaft formation is evident. figure 2b. the hair shaft is effaced without true hair formation. the follicle (h&e, 40x) shows abnormal, dense keratinization and excessive inner root sheath production. no outer root sheath is seen. the hair bulb lacks a papilla. figure 2c. nucleated eosinophilic cells (h&e, 40x) with excess trichohyaline and intraepithelial viral inclusions can be seen. the polyomaviridae virus is a small, nonenveloped double stranded dna virus. long-term infection with this virus is usually asymptomatic, but immunosuppression can lead to primary infection or reactivation, resulting in infection of the central nervous discussion skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 168 system, urinary tract, respiratory tract, and skin.1 in 2010, a new polyoma virus called trichodysplasia spinulosa‐associated polyomavirus (tspyv) by van der meijden et al was reported to be the cause of ts.1 this rare disease is known to affect immunocompromised hosts, most commonly after solid organ transplant. one recent review of 20 patients with ts found it to be associated with solid organ transplants in 13 cases and with leukemia or non-hodgkin lymphoma in 7 cases. ts is very rarely diagnosed in patients with hiv, perhaps because the degree of immunosuppression seen in patients treated with highly active antiretroviral therapy (haart) is not sufficient for disease progression. still, tspyv was found to be elevated on the skin of men with known hiv compared to controls.3 the current case is unique in that ts was diagnosed in an immunocompromised patient in the setting of both hiv infection and post-transplantation immunotherapy. clinically ts presents with follicular, erythematous, hyperkeratotic papules most often located on the central face, however it may also be found on the trunk and upper extremities. skin thickening and alopecia have also been noted.4 histologically, ts is characterized by abnormal hair follicles often without a formed hair shaft. excessive and disorganized inner root sheath cells, intraepithelial viral inclusions, and nucleated eosinophils containing excess trichohyaline can also be appreciated.5 management of ts is challenging, as this disease entity is newly described and rare. treatment options include topical cidofovir, topical acitretin, oral leflunomide, and manual extraction of keratin spicules (table i). this case highlights the safe use of topical cidofovir in a patient with a history of renal disease and transplant, though the oral antiviral counterpart is associated with nephrotoxicity. furthermore, this case highlights hyperpigmentation as a rare adverse event associated with the use of topical cidofovir. post-inflammatory hyperpigmentation was reported after the use of topical cidofovir for the treatment of molluscum contagiosum in 6 out of 14 patients with hiv.6 however, after a thorough review of the literature in pubmed, this case is the first to our knowledge to highlight a similar outcome in the setting of polyoma virus infection. though the patient presented here did not test positive for contact dermatitis related to the topical cidofovir, it should be noted that the preservative ingredients found in topical cidofovir base, mainly methylchloroisothiazolinone and methylisothiazolinone, have been increasingly associated with a delayed hypersensitivity reaction.7 dermatologists should be aware of this potentially common adverse event and counsel patients with ts accordingly. ts is a rare disease that affects immunosuppressed individuals. topical cidofovir appears to be the most commonly used treatment (table i). however, this unique case highlights a new and unreported adverse effect of hyperpigmentation in the setting of ts. dermatologists should be aware of this potential consequence and counsel patients appropriately. conclusion skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 169 table i. review of reported treatments for trichodysplasia spinulosa. treatment mechanism of action evidence adverse events topical cidofovir (1-3%) antiviral, which selective inhibits viral dna polymerase. successful resolution of ts lesions after 2-4 months.8-11 current case described hyperpigmentation adverse reaction. use of topical cidofovir for the treatment of molluscum contagiosum has been associated with hyperpigmentation in several cases.6 topical or oral acitretin speculated modulation of keratinocyte differentiation and hyperproliferation. minimal improvement of ts lesions after use of 20mg acitretin daily and tretinoin 0.05% daily, in a patient who ultimately improved due to recovered immune function.12 limited evidence of efficacy. oral leflunomide tyrosine kinase inhibitor, which inhibits replication of dna viruses. modification of immunosuppressive medications and leflunomide 100 mg daily orally for 5 days, followed by 40 mg daily for 1 month resulted in resolutions of lesions after 3 months.13 none reported. oral valganciclovir gancylcovir competitively inhibits dgtp incorporated in viral dna, thereby inhibiting viral replication. successful resolution of ts lesions in a case report with the use of 900mg valganciclovir bid.14 none reported. manual extraction physical removal of facial ts papules. successful resolution in a child after 2 months of repeated manual extraction.15 pain associated with manual extraction. skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 170 conflict of interest disclosures: none funding: none corresponding author: robert g phelps, md department of dermatopathology department of dermatology icahn school of medicine at mount sinai one gustave l levy place, new york, ny 10029 phone: 212-241-6500 email: robert.phelps@mountsinai.org references: 1. van der meijden e, janssens rw, lauber c, bouwes bavinck jn, gorbalenya ae, feltkamp mc. discovery of a new human polyomavirus associated with trichodysplasia spinulosa in an immunocompromized patient. plos pathogens. 2010;6(7):e1001024. 2. an p, saenz robles mt, duray am, cantalupo pg, pipas jm. human polyomavirus bkv infection of endothelial cells results in interferon pathway induction and persistence. plos pathogens. 2019;15(1):e1007505. 3. wieland u, silling s, hellmich m, potthoff a, pfister h, kreuter a. human polyomaviruses 6, 7, 9, 10 and trichodysplasia spinulosaassociated polyomavirus in hiv-infected men. the journal of general virology. 2014;95(pt 4):928-932. 4. haycox cl, kim s, fleckman p, et al. trichodysplasia spinulosa--a newly described folliculocentric viral infection in an immunocompromised host. the journal of investigative dermatology symposium proceedings. 1999;4(3):268-271. 5. decrescenzo aj, philips rc, wilkerson mg. trichodysplasia spinulosa: a rare complication of immunosuppression. jaad case reports. 2016;2(4):307-309. 6. calista d. topical cidofovir for severe cutaneous human papillomavirus and molluscum contagiosum infections in patients with hiv/aids. a pilot study. journal of the european academy of dermatology and venereology : jeadv. 2000;14(6):484-488. 7. scherrer ma, rocha vb, andrade ar. contact dermatitis to methylisothiazolinone. anais brasileiros de dermatologia. 2015;90(6):912914. 8. nguyen nv, burgos a, prok l. spiny papules in an immunosuppressed child. pediatric dermatology. 2015;32(6):e296-297. 9. coogle lp, holland ke, pan c, van why sk. complete resolution of trichodysplasia spinulosa in a pediatric renal transplant patient: case report and literature review. pediatric transplantation. 2017;21(2). 10. leitenberger jj, abdelmalek m, wang rc, strasfeld l, hopkins rs. two cases of trichodysplasia spinulosa responsive to compounded topical cidofovir 3% cream. jaad case reports. 2015;1(6):s33-35. 11. santesteban r, feito m, mayor a, beato m, ramos e, de lucas r. trichodysplasia spinulosa in a 20-month-old girl with a good response to topical cidofovir 1%. pediatrics. 2015;136(6):e1646-1649. 12. digiovanna jj, mauro t, milstone lm, schmuth m, toro jr. systemic retinoids in the management of ichthyoses and related skin types. dermatologic therapy. 2013;26(1):26-38. 13. kassar r, chang j, chan aw, lilly lb, al habeeb a, rotstein c. leflunomide for the treatment of trichodysplasia spinulosa in a liver transplant recipient. transplant infectious disease : an official journal of the transplantation society. 2017;19(4). 14. holzer am, hughey lc. trichodysplasia of immunosuppression treated with oral valganciclovir. journal of the american academy of dermatology. 2009;60(1):169-172. 15. barton m, lockhart s, sidbury r, wang r, brandling-bennett h. trichodysplasia spinulosa in a 7-year-old boy managed using physical extraction of keratin spicules. pediatric dermatology. 2017;34(2):e74-e76. mailto:robert.phelps@mountsinai.org m ea n efficacy and tolerance of a new non-steroidal prescription cream in the treatment of mild facial seborrheic dermatitis. fall clinical dermatology conference® october 12-15, 2017. las vegas, nevada, usa valderas-martinez p., garre a., granger c. innovation & development isdin s.a. barcelona spain introduction seborrheic dermatitis (sd) is a common, chronic, and relapsing dermatitis that is primarily patterned on sebum-rich parts of the face, retroauricular area, scalp, upper chest, and intertriginous areas causing flaking, scaling, inflammation and pruritus with er ythema. malassezia infection is an important pathogenic factor in sd. the density of this pathogen on the skin positively correlates with the severity of the disease. topical antifungal treatments reduce malassezia proliferation and the resulting inflammation, leading to the improvement of sd. the aim of this study was to evaluate the efficacy and safety of a non-steroidal cream, containing zinc pca, piroctone olamine, dihydroavenanthramide (symcalmin), biosaccharide gum-2 (rhamnosoft), and stear yl glycyrrhetinate in the treatment of mild.  methods we evaluated the clinical efficacy of the new, non steroidal prescription cream on 33 patients diagnosed with mild facial seborrheic dermatitis who were treated for 28 days.patients aged 18 years or older with sd on the face (iga=2) were included in the study. five centers participated in the study. the primary endpoint was to assess the efficacy using the investigator global assessment (iga) at day 28 ± 2 days as compared to baseline. secondary objectives included: iga after 10 days of treatment, investigator assessment of symptoms (er ythema, itching, scaling, stinging), subjective evaluation by patients of satisfaction of use, and quality of life using the skindex-29 score. the iga was rated using a 5-item score. results treatment proved successful in most patients (88%), and the iga with a reduction of the iga score at 28±2 days to 0.66 ± 0.94 compared to iga at 2 at baseline, sd was evaluated as absent in 56% of patients. after 10±2 days, treatment proved successful in most patients (79%), and the mean score of iga at this visit was 1.00±0.75 (figure 1). on the baseline visit, 100% of the patients had erythema, this percentage decreased to 41% at final visit (figure 2) with a mean intensity of erythema decreased from 1.18 ± 0.39 at baseline to 0.47±0.62 (figure 3). regarding patients satisfaction and qol, 78% of patients considered that the topical cream was good or excellent and the difference in total skindex-29 score between visits (baseline and final visit) was reduced by 5.85±7.05 (figure 4 and 5). none of the patients evaluated required rescue medication. there was 1 mild adverse reaction (erythema) during the study. isdin s.a.provencals, 33 barcelona spain iga score m ea n 2,5 2 1,5 1 0,5 0 d0 d10 d28 fi g u re 1 fi g u re 3 fi g u re 2 fi g u re 4 fi g u re 5 improvement of the erythema m ea n 1,8 1,6 1,4 1,2 1 0,8 0,6 0,4 0,2 0 -0,4 -0,2 d0 d10 d28 patient satisfaction 0,66±0,942±0iga score 1±0,75 skindex-29: quality of life score m ea n 30 25 15 10 5 0 20 functional dimension emotional dimension symptomatic dimension d0 d28 questionnaire: 0=very poor, 1=poor, 2=regular, 3=good, 4=excellent) g lo ba l r at in g (m ea n) improvement of symptoms of ds 100 80 60 40 20 0 erythema 67 ,0 0% the absorption of the product the texture of the product tolerance the quickness of action of applied product the effectiveness of the applied product 3, 34 3, 31 3, 09 3, 38 2, 94 40 ,6 0% 10 0, 00 % 21 ,0 0% 18 ,8 0% 10 0, 00 % 30 ,3 0% 18 ,2 0% 78 ,8 0% 21 ,2 0%3 6, 40 % 36 ,4 0% scaling itching stinging d0 d28d10 conclusions the use of this new non-steroidal prescription cream t h a t c o n t a i n s z i n c p c a , p i ro c to n e o l a m i n e , dihydroavenanthramide, biosaccharide gum-2, and stearyl glycyrrhetinate was shown to be effective in the treatment of mild facial seborrheic dermatitis. the product demonstrated a rapid efficacy profile after 10 days of treatment and was well tolerated by the patients. the quality of life of the patients (skindex-29) was improved. the product was well tolerated. fc17posterisdinnonsteroidcreamvalderas-martinez.pdf skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 315 brief article late onset junctional epidermolysis bullosa in adulthood evonne pei, ba1, sakeena fatima, md1, kory schrom, md1, ari konheim, md1 1 department of dermatology, university hospitals, cleveland, oh epidermolysis bullosa (eb) is a heterogenous group of blistering diseases of the skin and mucous membranes and is classified into four main types based on the location of the epidermal-dermal separation.1-3 junctional eb, an autosomal recessive variant, is characterized by its cleavage within the lamina lucida. the typical age of onset is at birth, and it can present with either generalized or localized mucocutaneous findings.3 a rare subtype of jeb is jeb of late onset (jeb-lo), which occurs in young adulthood or later with blisters primarily located on the hands and feet.2 other clinical features of this rare subtype include nail dystrophy, hyperhidrosis, loss of dermatoglyphs, and skin atrophy.2,4,5 we report a case of jeb-lo diagnosed in late adulthood. a 58-year-old man initially presented to our clinic in january 2021 with a 34-year history of a persistent rash on his bilateral lower extremities which he referred to as “eczema”. on examination, he was noted to have multiple erythematous papules coalescing into plaques with several superficial erosions on his bilateral anterior legs, with a few intact, tense bullae. he was also noted to have dystrophic changes of his toenails, including medial curvature of the nails and ingrown nails (figure 1). based on these features, our clinical differential diagnosis included epidermolysis bullosa, bullous pemphigoid or other autoimmune subepidermal blistering diseases, and two 4-mm punch biopsies were performed, one for h&e and one for dif. punch biopsy for h&e showed a subepidermal blister with occasional eosinophils. however, the dif studies were negative to all reactants used, making an autoimmune subepidermal blistering disease less likely (figure 2). after further discussion, immunomapping was pursued and two additional punch abstract epidermolysis bullosa (eb) is a heterogenous group of blistering diseases of the skin and mucous membranes and is classified into four main types based on the location of the epidermal-dermal separation.1-3 junctional eb, an autosomal recessive variant, is characterized by its cleavage within the lamina lucida. the typical age of onset is at birth, and it can present with either generalized or localized mucocutaneous findings.3 a rare subtype of jeb is jeb of late onset (jeb-lo), which occurs in young adulthood or later with blisters primarily located on the hands and feet.2 other clinical features of this rare subtype include nail dystrophy, hyperhidrosis, loss of dermatoglyphs, and skin atrophy.2,4,5 we report a case of jeb-lo diagnosed in late adulthood. introduction case report skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 316 figure 1. figure 2. biopsies, including one of an induced blister, were sent to stanford university medical center. immunofluorescence was stained with antibodies to basement membrane antigens, including lad-1 (123, collagen xvii), d4b5 (laminin 332 gamma ii chain), collagen iv, and collagen vii, which showed normal intensity staining with d4b5, collagen iv, and collagen vii with localization of these antigens to the blister floor. lad-1 showed relatively normal intensity staining but was absent in areas of the split with possible weak staining on the floor of the blister. overall, the findings were suggestive of junctional epidermolysis bullosa with mutation in col17a1, consistent with a late-onset variant of jeb. based on the patient’s history of recurrent tense blisters on his lower extremities, recent skin exams, histologic findings in his biopsy and negative dif studies as well as immunomapping, the most likely diagnosis is a late-onset variant of jeb due to a mutation in col17a1. upon further review of the patient’s history, his likely initial cutaneous manifestations were the development of his dystrophic toenails in his teenage years, which later required nail avulsion. around the age of 24 years old, he began developing tense blisters discussion skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 317 on his shins. he also has a history of dystrophic changes of his teeth necessitating dental crowns and root canals. he denies any oral lesions, hair abnormalities, or ocular lesions. family history is non-contributory. further examination did not reveal any involvement of his hands, including milia or changes in dermatoglyphs. the recommendations given to the patient included trauma avoidance and topical steroids for any symptoms of pruritus. jeb-lo is a rare subtype of jeb with varying clinical presentations. two jeb-lo patients described by yuen et al, a brother and sister, presented with blistering on the feet and around the toenails and fingernails starting at the age of 6 years old.2 both patients presented with loss of dermatoglyphs and waxy hyperkeratosis. two other siblings with jeb-lo were also reported by stouthamer et al.5 their onset of symptoms occurred at the age of 4 and 10 years old, with mechanobullous lesions, nail dystrophy, loss of dermatoglyphs, tooth enamel abnormalities, and hyperhidrosis.5 a 17-yearold boy diagnosed by vanotti et al has a homozygous missense mutation in col17a1 and blisters starting at the age of 8 years old with atrophic skin, abnormal dermatoglyphs, dystrophic nails, and speckled pigmentation on the elbows.6 the patient did not have hyperkeratosis or mucosal lesions. previous cases of jeb-lo reported within the literature had younger ages of onset and varying associated features compared to our patient. our case of jeb-lo is diagnosed in the oldest patient with the latest age of onset. this may be attributed to limited testing availability for the mutations involved, such as col17a1, leading to the underdiagnosis of jeb-lo. the patient also declined genetic testing. we report this case to highlight the existence of an exceedingly rare subtype of jeb that can be late onset and hope to increase clinician awareness. conflict of interest disclosures: none funding: none acknowledgments: dr. kerri rieger, md stanford health care corresponding author: evonne pei, ba email: exp272@case.edu references: 1. gannon ba. epidermolysis bullosa: pathophysiology and nursing care. neonatal netw. 2004 nov-dec;23(6):25-32. 2. yuen wy, pas hh, sinke rj, jonkman mf. junctional epidermolysis bullosa of late onset explained by mutations in col17a1. br j dermatol. 2011 jun;164(6):1280-4. 3. fine jd, bruckner-tuderman l, eady ra, bauer ea, bauer jw, has c, heagerty a, hintner h, hovnanian a, jonkman mf, leigh i, marinkovich mp, martinez ae, mcgrath ja, mellerio je, moss c, murrell df, shimizu h, uitto j, woodley d, zambruno g. inherited epidermolysis bullosa: updated recommendations on diagnosis and classification. j am acad dermatol. 2014 jun;70(6):1103-26. 4. yancey kb, hintner h. non-herlitz junctional epidermolysis bullosa. dermatol clin. 2010 jan;28(1):67-77. 5. stouthamer a, nieboer c, van der waal ri, jonkman mf. normal expression of the 19dej-1 epitope in two siblings with late-onset junctional epidermolysis bullosa. br j dermatol. 2001 may;144(5):1054-7. 6. vanotti s, chiaverini c, charlesworth a, bonnet n, berbis p, meneguzzi g, lacour jp. late-onset skin fragility in childhood: a case of junctional epidermolysis bullosa of late onset caused by a missense mutation in col17a1. br j dermatol. 2013 sep;169(3):714-5 conclusion tapinarof cream 1% once daily for plaque psoriasis: pooled efficacy from three phase 3 trials linda stein gold,1 mark lebwohl,2 robert bissonnette,3 bruce strober,4 anna m. tallman,5 philip m. brown,5 stephen c. piscitelli,5 david s. rubenstein5 1henry ford health system, detroit, mi, usa; 2icahn school of medicine, mount sinai, new york, ny, usa; 3innovaderm research inc., montreal, qc, canada; 4yale university, new haven, and central connecticut dermatology research, cromwell, ct, usa; 5dermavant sciences, inc., morrisville, nc, usa introduction ■ tapinarof (vtama®; dermavant sciences, inc., usa) is a first-in-class, non-steroidal, topical, aryl hydrocarbon receptor agonist approved by the food and drug administration for the treatment of plaque psoriasis in adults, and under investigation for the treatment of plaque psoriasis in children down to 2 years of age, and for atopic dermatitis (ad) in adults and children down to 2 years of age1 ■ tapinarof cream 1% once daily (qd) demonstrated statistically significant efficacy versus vehicle and was well tolerated in adults with mild to severe plaque psoriasis in two identical, 12-week, pivotal phase 3 trials, psoaring 1 (nct03956355) and psoaring 2 (nct03983980)2 – efficacy continued to improve beyond the 12-week trials in psoaring 3 (nct04053387), the long-term extension (lte) trial, with a high rate of complete disease clearance (physician global assessment [pga]=0; 40.9%), ~4-month remittive effect off therapy, and durability of response on therapy for up to 52 weeks3 ■ data from the two phase 3 trials and the lte trial have been pooled to evaluate the combined efficacy and safety of tapinarof cream 1% qd objective ■ to assess the efficacy and safety of tapinarof cream 1% qd using pooled data from three phase 3 trials, under conditions of continuous or intermittent treatment for up to 1 year methods trial design ■ the pooled efficacy analyses included all patients in the psoaring 1, 2, and 3 trials (figure 1) who had a baseline pga score of ≥2 before tapinarof treatment ■ these patients included the following: – patients randomized to tapinarof cream 1% qd in the psoaring 1 and 2 trials who may or may not have continued into the lte trial – patients randomized to vehicle in the psoaring 1 and 2 trials who continued into the lte trial, and had a pga score of ≥2 (mild or worse) before receiving treatment with tapinarof cream 1% qd in the lte trial ■ in psoaring 3, patients were treated with tapinarof cream 1% qd based on individual patient pga score: – patients who entered with a pga score of ≥1 received tapinarof cream until complete disease clearance was achieved (pga=0) – patients who entered with, or achieved, a pga score of 0 discontinued treatment and were observed for remittive effect (maintenance of pga=0 or 1), while off therapy – if disease worsening occurred (pga≥2), tapinarof cream was restarted and continued until a pga score of 0 was achieved figure 1. trial design for psoaring 1, 2, and 3 *patients with pga=2 (mild) and pga=4 (severe) limited to ~10% each of the total randomized population; ~80% of the total randomized population with pga=3 (moderate). †patients electing not to participate in the lte trial had a follow-up visit 4 weeks after completion of treatment period. bsa, body surface area; lte, long-term extension; pga, physician global assessment; qd, once daily; r, randomized. endpoints and statistical analysis ■ safety: adverse events (aes), laboratory values, vital signs, and physical exams ■ efficacy endpoints: – proportions of patients who achieved a pga score of 0 (clear) or 1 (almost clear), and ≥1-grade improvement in pga score at any time point – proportions of patients who achieved a 75% improvement in psoriasis area and severity index score (pasi75), and a 90% improvement in psoriasis area and severity index score (pasi90) at any time point ■ time-to-event parameters were summarized using the kaplan–meier product limit method, using observed cases results baseline patient demographics and disease characteristics ■ overall, 915 eligible patients were included in the pooled efficacy analyses (table 1) ■ overall, patients’ mean age was 50.2 years, 58.7% were male, mean weight was 92.2 kg, and mean body mass index was 31.6 kg/m2 ■ at baseline, 78.1% had a pga score of 3 (moderate), mean pasi score was 8.7, and mean body surface area affected was 7.8% table 1. baseline disease characteristics in pooled analyses tapinarof cream 1% qd (n=915) pga, n (%) 2 – mild 127 (13.9) 3 – moderate 715 (78.1) 4 – severe 73 (8.0) pasi, mean (sd) 8.7 (4.2) bsa affected, %, mean (sd) 7.8 (5.0) bsa, body surface area; pasi, psoriasis area and severity index; pga, physician global assessment; qd, once daily; sd, standard deviation. ■ figure 2 displays clinical response for a patient with plaque psoriasis treated with tapinarof cream 1% qd, whose improvement exceeded the pga, pasi75, and pasi90 endpoints by week 4 figure 2. clinical response of a patient with plaque psoriasis treated with tapinarof cream 1% qd example of one representative target lesion of one patient treated with tapinarof cream 1% qd from the psoaring 2 clinical trial. individual results may vary. bsa, body surface area; pasi, psoriasis area and severity index; pga, physician global assessment; qd, once daily. pga score outcomes ■ the proportion of patients with a ≥1-grade improvement in pga score increased over time: 77.4% of patients at week 12 and 80.9% at week 52, even with intermittent therapy ■ the proportion of patients with a pga score of 0 or 1 increased over time: 42.3% of patients at week 12 and 47.5% at week 52, even with intermittent therapy ■ 86.1% of patients (n=788) achieved a ≥1-grade improvement in pga score at any visit (figure 3a) ■ 62.0% of patients (n=567) achieved a pga score of 0 or 1 at any visit (figure 3b) figure 3. proportion of patients achieving a ≥1-grade improvement in pga score and a pga score of 0 or 1 at any time point *median time to a ≥1-grade improvement in pga score was 29 (95% ci, 29.0–31.0) days. †median time to a pga score of 0 or 1 was 112 (95% ci, 92.0–115.0) days. itt population, oc. ci, confidence interval; itt, intention-to-treat; oc, observed cases; pga, physician global assessment; qd, once daily. achieving pasi75 and pasi90 responses ■ the proportion of patients achieving a pasi75 response increased over time; this was achieved by 44.1% of patients at week 12 and 55.1% at week 52, even with intermittent therapy ■ the proportion of patients achieving a pasi90 response increased over time; this was achieved by 20.8% of patients at week 12 and 32.6% at week 52, even with intermittent therapy ■ 63.5% of patients (n=581) achieved a pasi75 response at any visit (figure 4a) ■ 44.2% of patients (n=404) achieved a pasi90 response at any visit (figure 4b) figure 4. proportion of patients achieving pasi75 and pasi90 responses at any time point *median time to a pasi75 response was 111 (95% ci, 89–113) days. †median time to a pasi90 response was 225 (95% ci, 197–252) days. itt population, oc. ci, confidence interval; itt, intention-to-treat; oc, observed cases; pasi75, ≥75% improvement in psoriasis area and severity index score; pasi90, ≥90% improvement in psoriasis area and severity index score; qd, once daily. safety ■ treatment-emergent aes (teaes) were mostly mild to moderate ■ the most common teaes (in ≥5% of patients) were folliculitis, contact dermatitis, and nasopharyngitis conclusions ■ these pooled analyses from the three phase 3 trials further demonstrated the efficacy and safety of tapinarof cream 1% qd to treat mild to severe plaque psoriasis under conditions of continuous or intermittent treatment for up to 1 year ■ efficacy increased over time through 52 weeks across multiple endpoints, even with intermittent therapy ■ safety outcomes were consistent with the individual phase 3 trials ■ these analyses provide additional, robust evidence that tapinarof cream 1% qd represents a first-in-class, non-steroidal, topical therapy for patients with plaque psoriasis that is effective and well tolerated with long-term use, including on intertriginous and sensitive skin areas references 1. dermavant sciences. vtama (tapinarof) cream, 1%: us prescribing information. 2022. https://www.vtama.com/docs/dmvt_vtama_pi.pdf. accessed july 2022. 2. lebwohl m, et al. n engl j med. 2021;385:2219–2229. 3. strober b, et al. j am acad dermatol. 2022. https://doi.org/10.1016/j.jaad.2022.06.1171. acknowledgments this trial was funded by dermavant sciences, inc. the authors thank the participating investigators, patients and their families, and colleagues involved in the conduct of the trial. l.s.g. has served as a consultant, and/or has received payment for the development of educational presentations, and/or has received grants from arcutis, amgen, bristol myers squibb, dermavant sciences, inc., eli lilly, leo pharma, ortho dermatologic, and ucb biopharma. m.l. has received grants, and/or is a consultant for abbvie, amgen, aditum bio, almirall, altrubio inc., anaptysbio, arcutis, aristea therapeutics, arrive technologies, avotres, biomx, boehringer ingelheim, bristol myers squibb, cara therapeutics, castle biosciences, corrona, dermavant sciences, inc., dr. reddy’s laboratories, eli lilly, evelo biosciences, evommune, inc., facilitation of international dermatology education, forte biosciences, foundation for research and education in dermatology, helsinn therapeutics, hexima ltd, incyte, janssen research & development, leo pharma, llc, meiji seika pharma, mindera, ortho dermatologics, pfizer, regeneron, seanergy, ucb, inc., and verrica. r.b. has served as a consultant/advisory board member/ speaker/investigator, and/or receives honoraria/grants from almirall, amgen, anaptysbio, arcutis, arena pharma, aristea, asana biosciences, bausch health, bellus health, bluefin biomedicine, boehringer ingelheim, bristol myers squibb, cara, dermavant sciences, inc., eli lilly, emd serono, escalier, evidera, galderma, glaxosmithkline, incyte, inmagene bio, janssen, kiniksa, kyowa kirin, leo pharma, nimbus, novan, pfizer, ralexar, rapt, regeneron, respivant, sanofi genzyme, sienna, target rwe, and ucb biopharma. r.b. is an employee and shareholder of innovaderm research. b.s. has served as an honorary consultant/speaker/scientific director/investigator for abbvie, almirall, amgen, arcutis, arena, aristea, boehringer ingelheim, bristol myers squibb, cara, celgene, corrona psoriasis registry, dermavant sciences, inc., dermira, equillium, glaxosmithkline, janssen, leo, eli lilly, meiji seika pharma, mindera, novartis, ortho dermatologics, pfizer, regeneron, sanofi-genzyme, sun pharma, and ucb pharma. a.m.t., p.m.b., s.c.p., and d.s.r. are employees of dermavant sciences, inc., with stock options. editorial and medical writing support under the guidance of the authors was provided by apothecom, uk, and was funded by dermavant sciences, inc. in accordance with good publication practice (gpp3) guidelines (ann intern med. 2015;163:461–464). contact dr linda stein gold at lstein1@hfhs.org with questions or comments. adult patients with plaque psoriasis • aged 18–75 years • pga score ≥2* • bsa ≥3% to ≤20% double-blind treatment (12 weeks) 2:1 2:1 tapinarof 1% qd (n=340) tapinarof 1% qd (n=343) vehicle qd (n=170) vehicle qd (n=172) (n=510) (n=515) r r off treatment off treatment pga=0 (n=79) pga=0 stop treatment pga≥2 re-start treatment pga≥1 (n=680) tapinarof 1% qd long-term open-label extension† (40 weeks) follow-up (4 weeks) • pga=3 • pasi=14.7 • bsa=15.3% baseline week 4 week 12 • pga=1 • pasi=0.9 • bsa=0.3% • pga=0 • pasi=0 • bsa=0% 0 10 20 30 40 50 60 80 100 90 70 tapinarof 1% qd (n=915) 86% p ro p o rt io n o f p at ie n ts , % 0 10 20 30 40 50 60 80 100 90 70 tapinarof 1% qd (n=915) 62% p ro p o rt io n o f p at ie n ts , % a. ≥1-grade improvement in pga score* b. pga score of 0 or 1† 0 10 20 30 40 50 60 80 100 90 70 tapinarof 1% qd (n=915) 64% p ro p o rt io n o f p at ie n ts , % 0 10 20 30 40 50 60 80 100 90 70 tapinarof 1% qd (n=915) 44% p ro p o rt io n o f p at ie n ts , % a. pasi75 response* b. pasi90 response† powerpoint presentation objective efficacy and safety of tralokinumab in adolescents with moderate-to-severe atopic dermatitis: results of the phase 3 ecztra 6 trial amy paller,1 andrew blauvelt,2 weily soong,3 shinichi imafuku,4 chih-ho hong,5 marie l.a. schuttelaar,6 petra amoudruz,7 azra kurbasic,7 lise soldbro,7 katja lophaven,7 michael cork,8 anthony bewley,9 eric l. simpson10 • atopic dermatitis (ad) is a chronic, pruritic, inflammatory skin disease that can negatively impact quality of life in adolescents1 • negative impacts of ad include effects on school performance, social relationships, participation in sports and increased rates of anxiety, depression, and suicidal ideation2-4 • tralokinumab is a fully human, high-affinity, monoclonal antibody that specifically neutralizes interleukin (il)-13, a key driver of skin barrier dysfunction, inflammation and dysbiosis in ad5-9 • in adult phase 3 trials, tralokinumab demonstrated efficacy and safety for treatment of ad10 study design (figure 1) to evaluate the efficacy and safety of tralokinumab in adolescents with moderate-to-severe ad in the phase 3 ecztra 6 trial (nct03526861) placebo (n=94) tralokinumab 150 mg q2w (n=98) tralokinumab 300 mg q2w (n=97) mean age, years 14.3 14.8 14.6 age group 12-14, n (%) 49 (52.1) 37 (37.8) 45 (46.4) 15-17, n (%) 45 (47.9) 61 (62.2) 52 (53.6) male, n (%) 51 (54.3) 51 (52.0) 47 (48.5) race/ethnicity, n (%) white 53 (56.4) 55 (56.1) 56 (57.7) black or african american 11 (11.7) 7 (7.1) 14 (14.4) asian 23 (24.5) 28 (28.6) 20 (20.6) hispanic or latino 6 (6.4) 10 (10.2) 9 (9.3) mean duration of ad, years (sd) 12.7 (3.7) 12.1 (3.7) 12.1 (3.5) mean bsa involvement with ad, % (sd) 51.4 (23.9) 52.4 (22.6) 49.6 (23.3) severe disease (iga=4), n (%) 43 (45.7) 44 (44.9) 48 (49.5) mean easi (sd) 31.2 (14.5) 32.1 (12.9) 31.8 (13.9) mean scorad (sd) 67.4 (14.9) 67.7 (14.4) 68.3 (13.7) mean cdlqi (sd) 13.3 (6.0) 12.9 (6.3) 13.4 (7.3) mean weekly average worst daily pruritus nrs score (sd) 7.5 (1.7) 7.5 (1.6) 7.8 (1.5) 1feinberg school of medicine, northwestern university, chicago il, usa; 2oregon medical research center, portland, or, usa; 3allervie health-alabama allergy & asthma center, birmingham, al, usa; 4fukuoka university, fukuoka, japan; 5university of british columbia, vancouver, bc, canada; 6university medical centre groningen, university of groningen, groningen, the netherlands; 7leo pharma a/s, ballerup, denmark; 8university of sheffield, sheffield, uk; 9barts health nhs trust, london, uk; 10oregon health & science university, portland, or, usa introduction materials and methods • adolescent patients were randomized 1:1:1 to subcutaneous tralokinumab 150 mg or 300 mg every 2 weeks (q2w), or placebo for an initial treatment period of 16 weeks • co-primary endpoints were investigator’s global assessment (iga) score 0/1 and ≥75% improvement in eczema area and severity index (easi-75) at week 16 • patients achieving primary endpoints without rescue treatment were rerandomized to tralokinumab q2w or every 4 weeks (q4w), at their same initial dosage for 36 weeks of maintenance treatment as shown in figure 1 • patients not achieving primary endpoints at week 16, those receiving rescue treatment from week 2 to week 16, and those meeting other specific criteria† were transferred to open-label treatment of tralokinumab 300 mg q2w plus optional mild-to-moderate strength topical corticosteroids (tcs) • easi-75, iga 0/1, and secondary endpoint ≥4-point improvement in adolescent pruritus numerical rating scale (nrs) were analyzed using cochran-mantelhaenszel test stratified by geographic region and baseline disease severity • patients receiving rescue therapy between week 2 and 16 or with missing data at week 16 were considered non-responders • secondary endpoints, change from baseline in scoring ad (scorad) and children’s dermatology life quality index (cdlqi) were analyzed using a linear mixed model for repeated measurements • data after use of rescue or discontinuation were disregarded • a closed testing procedure with hierarchical tests, alpha splitting, and alpha recycling were applied for above efficacy endpoints • the safety population was defined as all randomized patients who received ≥1 injection of study drug statistical analyses and endpoints figure 1. ecztra 6 study design table 1. baseline characteristics patient characteristics • baseline demographic and clinical characteristics were comparable across treatment groups (table 1) bsa: body surface area. ad: atopic dermatitis. n: number of subjects in analysis set. q2w: every 2 weeks. iga: investigator's global assessment. easi: eczema area and severity index. scorad: scoring atopic dermatitis. cdlqi: children's dermatology life quality index. nrs: numeric rating scale. references disclosures safety through week 16 • through week 16, percentages of adverse events (aes), serious aes, aes leading to discontinuation, and conjunctivitis events were similar between the tralokinumab (150 mg/300 mg) and placebo treatment groups (table 2) • the majority of aes in all treatment groups were mild or moderate in severity and subjects recovered from most of the aes conclusions • at week 16, tralokinumab 150 mg and 300 mg q2w demonstrated significant efficacy vs placebo across primary and secondary endpoints in adolescents with moderate-tosevere ad • tralokinumab was well tolerated; efficacy and safety profiles were comparable to those in phase 3 adult tralokinumab trials 1. marciniak j. acta derm venereol. 2017;97(6):711–714. doi: 10.2340/00015555-2633. 2. ricci g. dermatol reports. 2011;4(1):e1. doi: 10.4081/dr.2012.e1. 3. slattery m. j allergy clin immunol. 2011; 128(3):668–671.e3. doi: 10.1016/j.jaci.2011.05.003. 4. halvorsen j. j invest dermatol. 2014;134(7):1847–1854. doi: 10.1038/jid.2014.70. 5. bieber t. allergy. 2020;75(1):54-62. doi: 10.1111/all.13954. 6. furue k et al. immunology. 2019; 158(4): 281-286. doi: 10.1111/imm.13120. 7. szegedi k et al. jeadv. 2015;29(11):2136–2144. doi: 10.1111/jdv.13160. 8. tsoi lc et al. j invest dermatol. 2019;139(7):1480-1489. doi: 10.1016/j.jid.2018.12.018. 9. popovic b et al. j mol biol. 2017; 429(2): 208–219. doi: 10.1016/j.jmb.2016.12.005. 10. wollenberg a. br j dermatol. 2021; 184(3):437–449. doi: 10.1111/bjd.19574. amy paller has served as an investigator for abbvie, anaptysbio, incyte, janssen, krystalbio, leo pharma, regeneron, and ucb, received honorarium for consultancy from abbvie, abeona, almirall, anaptysbio, arena, azitra, biomx, boehringer ingelheim, castle biosciences, catawba, dermira, exicure, forté, kamari, leo pharma, lilly, lifemax, novartis, pfizer, regeneron, sanofi genzyme, seanergy, and ucb, and served on a data safety monitory board for abbvie, bausch, galderma, and novan. andrew blauvelt is a scientific adviser and clinical study investigator for abbvie, abcentra, aligos, almirall, amgen, arcutis, arena, aslan, athenex, boehringer ingelheim, bristol-myers squibb, dermavant, eli lilly, evommune, forte, galderma, incyte, janssen, landos, leo pharma, novartis, pfizer, rapt, regeneron pharmaceuticals, inc., sanofi genzyme, sun pharma, ucb pharma. weily soong has served on the advisory board and received research grants from abbvie, leo, genentech, inc., teva, novartis, and pfizer; served on the advisory board, received research grants, and was a speaker for amgen, astrazeneca, regeneron, sanofi, and glaxosmithkline; received research grants and was a speaker for optinose; received research grants from aimmune, avillion, galderma, gossamer bio, 3m, and leo pharma. shinichi imafuku is a researcher, consultant, or speaker for abbvie, amgen, celgene, daiichisankyo, eisai, kyowakirin, lilly, taihoyakuhinkogyo, tanabemitsubishi, tsumura, torii, maruho, novartis, leo pharma and janssen. chih-ho hong is a researcher, consultant, and/or advisor for abbvie, amgen, arcutis, bausch health, boehringer ingelheim, celgene, dermavant, dermira, ds biopharma, galderma, glaxosmithkline, incyte, janssen, leo pharma, lilly, medimmune, novartis, pfizer, regeneron, roche, sanofi genzyme, sun pharma, and ucb. marie l.a. schuttelaar has served on advisory boards for sanofi genzyme, pfizer, leo pharma, eli lilly, galderma, and abbvie; as an investigator for abbvie, novartis, regeneron pharmaceuticals, inc., sanofi genzyme, and galderma; as a consultant for regeneron pharmaceuticals, inc.; has received research grants from sanofi genzyme and novartis. petra amoudruz, azra kurbasic, lise soldbro, and katja lophaven are employees of leo pharma a/s. michael cork has served as a clinical trial investigator for astellas, galapagos, johnson & johnson, leo pharma, la roche-posay, msd, novartis, perrigo, regeneron, sanofi genzyme, and stiefel; has served as an advisory board member, consultant, and/or invited lecturer for pfizer inc., amgen, astellas, bayer, johnson & johnson, leo pharma, l’oréal, msd, novartis, regeneron, sanofi genzyme, stiefel, and unilever; has received honoraria from astellas, johnson & johnson, leo pharma, novartis, regeneron, sanofi genzyme, and stiefel; and has received research funding from bayer. anthony bewley has been a consultant for and received consultancy fees or travel bursaries from abbvie, almiral, eli lilly, galderma, janssen, leo pharma, novartis, sanofi and ucb pharma. eric simpson is a consultant and investigator for regeneron/sanofi, dermira, menlo pharmaceuticals, lilly, abbvie, genentech, medimmune, gsk, leo pharma, celgene, and pfizer. acknowledgements • the ecztra 6 clinical trial was sponsored by leo pharma a/s, ballerup, denmark • medical writing and editorial support from alphabet health by clair geary, phd, was funded by leo pharma a/s, ballerup, denmark • this work was previously presented at fall clinical dermatology conference, oct 21-24, 2021 table 2. summary of aes from week 0 to 16 figure 2. tralokinumab treatment demonstrated efficacy vs placebo across endpoints at week 16. a. iga 0/1 b. easi-75 c. ≥4-point improvement in adolescent pruritus nrs d. change in scorad e. change in cdlqi a b c d • age 12 – 17 • history of ad for ≥1 year • bsa involvement ≥10% at screening and baseline • easi score ≥12 at screening and ≥16 at baseline • iga score ≥3 at screening and baseline • history of tcs and/or topical calcineurin inhibitor treatment failure, or subjects for whom these treatments are medically inadvisable • stable dose of emollient ≥2 times daily for ≥14 days before randomization key inclusion criteria results • at week 16, significantly greater proportions of patients receiving tralokinumab achieved the primary endpoints of iga 0/1 and easi-75 without use of rescue compared to those receiving placebo (figure 2a, b) • significantly greater proportions of patients receiving tralokinumab vs placebo achieved ≥4-point improvement in adolescent pruritus nrs at week 16 without use of rescue (figure 2c) • tralokinumab treatment was associated with greater improvement than placebo in scorad and cdlqi from baseline to week 16 (figure 2d, e) week 16 efficacy analyses e placebo (n=94) tralokinumab 150 mg q2w (n=98) tralokinumab 300 mg q2w (n=97) patient-years of exposure 27.93 29.33 29.48 aes, n (%) 58 (61.7) 66 (67.3) 63 (64.9) saes 5 (5.3) 3 (3.1) 1 (1.0) aes leading to discontinuation 0 1 (1.0) 0 severity, n (%) mild 40 (42.6) 48 (49.0) 47 (48.5) moderate 31 (33.0) 33 (33.7) 32 (33.0) severe 7 (7.4) 5 (5.1) 3 (3.1) aes of special interest eye disorders 2 (2.1) 4 (4.1) 4 (4.1) conjunctivitis 2 (2.1) 4 (4.1) 3 (3.1) eczema herpeticum 1 (1.1) 1 (1.0) 0 skin infections requiring systemic treatment 2 (2.1) 5 (5.1) 2 (2.1) injection site reactions 1 (1.1) 9 (9.2) 7 (7.2) *loading dose of 600 mg for patients receiving 300 mg q2w or 300 mg for those receiving 150 mg q2w †patients not achieving easi-75 over ≥4 weeks with iga ≥2 after iga=0 at week 16, or with iga ≥3 after iga=1 at week 16, or who had iga >1 at week 16; patients who receive rescue treatment after week 16 ad, atopic dermatitis; easi, eczema area and severity index; iga, investigator’s global assessment; q2w, every 2 weeks; q4w, every 4 weeks; tcs, topical corticosteroids. tralokinumab 150 mg q2w placebo q2w tralokinumab 150 mg q2w tralokinumab 150 mg q4w alternating with placebo placebo q2w tralokinumab 300 mg q2w plus optional tcs initial treatmentscreening maintenance treatment patients with clinical response iga-0/1 or easi-75 without rescue safety follow-up open-label treatment 1:1:1 randomization • patients not achieving iga=0/1 or easi-75 week 16 • patients receiving rescue treatment from week 2 to week 16 • patients meeting specific criteria† washout of previous ad treatment (2 weeks for tcs) after initial loading dose* 1:1 16 weeks0–6 weeks 52 weeks 66 weeks tralokinumab 300 mg q2w tralokinumab 300 mg q2w tralokinumab 300 mg q4w alternating with placebo 1:1 error bars show 95% confidence intervals. p-values compare respective tralokinumab dose to placebo. tables show the number of patients who had a valid measurement value at the specified week. q2w: every 2 weeks. iga: investigator's global assessment. easi: eczema area and severity index. nrs: numeric rating scale. scorad: scoring atopic dermatitis. cdlqi: children's dermatology life quality index. 0 2 4 6 8 10 12 14 16 0 10 20 30 week ig a 0 / 1 r e s p o n d e rs ( % ) tralokinumab 300 mg (n=97) placebo (n=94) tralokinumab 150 mg (n=98) 4.3 21.4 17.5 0 2 4 6 8 10 12 14 16 0 10 20 30 40 50 week e a s i7 5 r e s p o n d e rs ( % ) tralokinumab 300 mg (n=97) placebo (n=94) tralokinumab 150 mg (n=98) 6.4 28.6 27.8 0 2 4 6 8 10 12 14 16 0 10 20 30 40 week a d o le sc e n t p ru ri tu s n r s ≥ 4 r e s p o n d e rs ( % ) tralokinumab 300 mg (n=96) placebo (n=90) tralokinumab 150 mg (n=95) 3.3 23.2 25.0 0 2 4 6 8 10 12 14 16 -40 -30 -20 -10 0 week c h a n g e i n s c o r a d f ro m b a s e lin e tralokinumab 300 mg placebo tralokinumab 150 mg -9.5 -27.5 -29.1 0 2 4 6 8 10 12 14 16 -10 -8 -6 -4 -2 0 week c h a n g e i n c d l q i fr o m b a se lin e tralokinumab 300 mg placebo tralokinumab 150 mg -4.1 -6.1 -6.7 94 94 69 66 53 47 44 24 35 98 98 85 76 72 69 65 62 61 97 97 87 81 77 71 71 67 66 placebo tralokinumab 150 mg tralokinumab 330 mg 89 88 63 60 49 41 33 95 93 80 70 69 63 58 94 93 83 79 76 67 65 placebo tralokinumab 150 mg tralokinumab 330 mg ; p=0.04 ; p=0.007 ; p<0.001 ; p<0.001 ; p<0.001 ; p<0.001 ; p<0.001 ; p=0.002 ; p<0.001 ; p=0.001 acknowledgements: medical writing support was provided by prescott medical communications group (chicago, il) with financial support from ortho dermatologics; ortho dermatologics is a division of bausch health us, llc • presented at winter clinical dermatology conference 2022 • january 14-19, 2022 • kauai, hi synopsis � acne is often regarded as an adolescent condition, but incidence among adults— especially females—is increasingly common1 � acne in females ≥25 years of age (referred to as adult female acne) may have a different etiology, presentation, burden, and response to treatment than acne in females 18–24 years old (referred to as postadolescent acne)1,2 • this may be due to a “transition period” for females aged 18–24 years, wherein some have acne that is more adolescent in nature, whereas older females in this cohort may be transitioning to acne associated with the adult female patient � adult female acne is also associated with dry skin, and treatment-related irritation is a significant concern2 � a recently approved, lower-dose tazarotene 0.045% lotion formulation (arazlo®; ortho dermatologics) was developed utilizing polymeric emulsion technology (figure 1)3 • this highly spreadable lotion formulation was developed to allow for more efficient delivery of tazarotene into dermal layers while reducing the potential for irritation figure 1. polymeric emulsion technology for tazarotene 0.045% lotion ① polymeric matrix holds water and water-soluble hydrating agents within a 3-d mesh ② droplets of tazarotene and oil-soluble moisturizing agents held apart by the 3-d mesh ③ 3-d mesh allows for uniform distribution of tazarotene and moisturizing agents 25-50 μm 1-2 μm ① ② ③ objective � to evaluate efficacy, safety, and impact on quality of life of tazarotene 0.045% lotion in adult females ≥18 years or ≥25 years of age methods � in two phase 3, double-blind, vehicle-controlled studies, eligible participants aged ≥9 years with moderate-to-severe acne were randomized 1:1 to tazarotene 0.045% lotion or vehicle once daily for 12 weeks • cerave® hydrating cleanser and cerave® moisturizing lotion (l’oreal, ny) were provided as needed for optimal moisturization/cleaning of the skin � data from these studies were pooled and analyzed post hoc for female participants categorized by age: ≥18 years or ≥25 years � endpoints included mean reductions in inflammatory/noninflammatory lesion counts, percentage of participants achieving treatment success (≥2-grade reduction in evaluator’s global severity score [egss] and a score of 0 [‘clear’] or 1 [‘almost clear’]), and the acne-specific quality of life questionnaire (acne-qol); treatmentemergent adverse events (teaes) were also assessed figure 2. efficacy outcomes at week 12 by age group (itt population, pooled) -30% -70% -50% ≥18 years ls m e a n c h a n g e f ro m b a se lin e 0% a. in�ammatory lesion reduction -53.7% -60.6% ** ≥25 years -57.3% -60.9% vehicle lotiontazarotene 0.045% lotion -10% n= 374 n= 370 n= 167 n= 168 -30% -70% -50% ≥18 years 0% b. nonin�ammatory lesion reduction -48.4% -59.0% *** ≥25 years -48.8% -61.1% ** -10% n= 374 n= 370 n= 167 n= 168 40% 0% 20% ≥18 years p e rc e n ta g e o f p a rt ic ip a n ts 100% c. treatment successa 24.8% ** 35.8% ≥25 years 26.1% 35.9% 60% n= 374 n= 370 n= 167 n= 168 80% vehicle lotiontazarotene 0.045% lotion vehicle lotiontazarotene 0.045% lotion **p<0.01; ***p<0.001 vs vehicle. adefined as ≥2-grade reduction from baseline in evaluator’s global severity score and a score of 0 (‘clear’) or 1 (‘almost clear’). itt, intent to treat; ls, least-squares. figure 3. acne-qol improvements at week 12 by age group (itt population, pooled) 8 0 2 4 6 ≥18 years m e a n c h a n g e f ro m b a se lin e to w e e k 1 2 14 a. self-perception 9.5 10.9 ≥25 years 10.0 10.7 vehicle lotion tazarotene 0.045% lotion 12 10 n= 313 n= 303 n= 143 n= 137 8 0 2 4 6 ≥18 years 14 b. role-emotional 7.8 8.8 ≥25 years 8.4 9.0 vehicle lotion tazarotene 0.045% lotion 12 10 n= 313 n= 303 n= 143 n= 137 8 0 2 4 6 ≥18 years 14 c. role-social 6.2 6.6 ≥25 years 6.76.4 vehicle lotion tazarotene 0.045% lotion 12 10 n= 312 n= 303 n= 142 n= 137 8 0 2 4 6 ≥18 years 14 d. acne symptoms 7.1 * 8.3 ≥25 years 7.5 8.1 vehicle lotion tazarotene 0.045% lotion 12 10 n= 313 n= 303 n= 143 n= 137 im p ro ve m e n t *p<0.05 vs vehicle. higher scores for each domain in acne-qol reflect increased health-related quality of life. self-perception, role-emotional, and acne symptoms domain score ranges are 0 to 30; role-social domain score range is 0 to 24; a positive mean change indicates a favorable result. acne-qol, acne-specific quality of life; itt, intent to treat. figure 4. acne improvements in tazarotene-treated adult females 18-year-old female 32-year-old female protocol: v01-123a-302 | site: 229 | subject: 229006 | initials: otd visit: baseline day 0 | visit date: 21sep2017 | view: right | treatment: idp-123 lotion baseline egss=3 protocol: v01-123a-302 | site: 234 | subject: 234029 | initials: sec visit: baseline day 0 | visit date: 05feb2018 | view: right | treatment: idp-123 lotion baseline egss=3 protocol: v01-123a-302 | site: 229 | subject: 229006 | initials: otd visit: week 12 | visit date: 13dec2017 | view: right | treatment: idp-123 lotion week 12 egss=1 protocol: v01-123a-302 | site: 234 | subject: 234029 | initials: sec visit: week 12 | visit date: 01may2018 | view: right | treatment: idp-123 lotion week 12 egss=1 individual results may vary. egss, evaluator’s global severity score. tazarotene 0.045% lotion for females with acne: analysis of two different adult age groups neil sadick, md1,2; fran e cook-bolden, md1,3; kenneth beer, md4; zoe d draelos, md5; leon h kircik, md6,7,8; emil a tanghetti, md9; eric guenin, pharmd, phd, mph10 1department of dermatology, weill cornell medical college; 2sadick dermatology, new york, ny; 3fran e. cook-bolden, md, pllc; 4university of miami miller school of medicine, miami, fl; 5dermatology consulting services, pllc, high point, nc; 6indiana university school of medicine, indianapolis, in; 7physicians skin care, pllc, louisville, ky; 8icahn school of medicine at mount sinai, new york, ny; 9center for dermatology and laser surgery, sacramento, ca; 10ortho dermatologics,* bridgewater, nj *ortho dermatologics is a division of bausch health us, llc results participants � of the 1614 participants in the pooled population, over 65% (n=1064) were females; of these, almost three-fourths were adults (≥18 years, n=744; ≥25 years, n=335) � more than 90% of female participants in both age groups had a baseline egss score of 3 (‘moderate’; table 1) table 1. participant demographics and baseline characteristics (itt population, pooled) females ≥18 y (n=744) females ≥25 y (n=335) age, mean (sd), y 25.2 (6.4) 30.6 (5.9) age, median (range), y 24.0 (18–65) 29.0 (25–65) ethnicity, hispanic/latino, n (%) 153 (20.6) 71 (21.2) race, n (%) white 510 (68.5) 203 (60.6) black 161 (21.6) 97 (29.0) asian 37 (5.0) 19 (5.7) othera 36 (4.8) 16 (4.8) inflammatory lesion count, mean (sd) 27.3 (6.8) 26.9 (6.6) noninflammatory lesion count, mean (sd) 38.6 (14.6) 38.2 (14.7) evaluator’s global severity score, n (%) 3 – moderate 687 (92.3) 312 (93.1) 4 – severe 57 (7.7) 23 (6.9) aincludes american indian or alaska native and other/multiple. egss, evaluator’s global severity score; itt, intent to treat. efficacy and quality of life � at week 12, female participants in both age groups had approximately 60% reductions from baseline in inflammatory and noninflammatory lesion counts with tazarotene 0.045% lotion (figure 2a–b) � over one-third of tazarotene-treated females in both age groups achieved treatment success at week 12 (figure 2c) � all efficacy endpoints were significantly improved (p<0.05) with tazarotene versus vehicle for females ≥18 years, and noninflammatory lesions were significantly improved for females ≥25 years; the lack of statistical significance for females ≥25 years for inflammatory lesion reduction and treatment success may have been due to the smaller sample size and/or relatively larger vehicle response (figure 2) � acne-qol domain scores improved from baseline to week 12 in both age groups; improvements were generally similar between age groups and greater with tazarotene 0.045% lotion than with vehicle (figure 3) � images of representative tazarotene-treated participants from each age group are shown in figure 4. safety � teae rates/severity/relationship to study drug and the most common teaes were generally similar for tazarotene-treated females in both age groups (table 2); most teaes were mild to moderate in severity • rates of treatment-related application site dryness and exfoliation were slightly higher among females ≥25 years than females ≥18 years, consistent with the association between adult female acne and dry skin � rates of application site irritation related to tazarotene treatment were low for both female age groups (≥18 years, 1.1%; ≥25 years, 0.6%) table 2. treatment-emergent adverse events (safety population, pooled) participants, n (%) females ≥18 years females ≥25 years taz 0.045% lotion (n=358) vehicle lotion (n=359) taz 0.045% lotion (n=162) vehicle lotion (n=158) reporting any teae 117 (32.7) 61 (17.0) 54 (33.3) 23 (14.6) discontinued due to a teaea 14 (3.9) 4 (1.1) 6 (3.7) 1 (0.6) severity of teaes reported mild 75 (20.9) 27 (7.5) 36 (22.2) 11 (7.0) moderate 35 (9.8) 31 (8.6) 17 (10.5) 11 (7.0) severe 7 (2.0) 3 (0.8) 1 (0.6) 1 (0.6) relationship to study drug related 53 (14.8) 8 (2.2) 27 (16.7) 2 (1.3) unrelated 64 (17.9) 53 (14.8) 27 (16.7) 21 (13.3) most common treatment-related teaesb application site pain 23 (6.4) 2 (0.6) 10 (6.2) 0 application site dryness 19 (5.3) 1 (0.3) 11 (6.8) 0 application site exfoliation 12 (3.4) 0 7 (4.3) 0 application site erythema 7 (2.0) 0 3 (1.9) 0 aincludes participants who discontinued study drug or prematurely discontinued from study. breported in ≥2% of participants in any treatment group. taz, tazarotene; teae, treatment-emergent adverse event. conclusions � efficacy and tolerability of topical treatments is important for all patients with acne; among adult females aged ≥18 years and ≥25 years—who comprised a large percentage of the pooled study population—treatment with tazarotene 0.045% lotion reduced inflammatory and noninflammatory lesions by approximately 60% � quality of life improvements were similar for both age groups, though improvements across all four acne-qol domains following tazarotene treatment were more substantial in these female participants than the overall population4 (data not shown) • these results are not unexpected, as studies have shown that in females with acne, anxiety/depression are more likely and acne improvements positively affect quality of life5; furthermore, females of all ages have been shown to have relatively greater quality of life improvements with tazarotene 0.045% lotion than males6 � tazarotene lotion was well tolerated in both female age groups; although treatment-related irritation is of particular concern for females ≥25 years,2 application site irritation with tazarotene 0.045% lotion was <1% in this population � these results demonstrate that tazarotene 0.045% lotion is a viable treatment option for females with either postadolescent or adult female acne references 1. dréno b, et al. j eur acad dermatol venereol. 2015;29(6):1096–1106. 2. zeichner ja, et al. j clin aesthet dermatol. 2017;10(1):37–46. 3. tanghetti ea, et al. j drugs dermatol. 2019;18(6):543–548. 4. kircik lh, et al. j drugs dermatol. 2020;10(11):1086–1092. 5. skroza n, et al. g ital dermatol venereol. 2016;151(1):87–92. 6. kircik lh, et al. j drugs dermatol. 2020;19(11):1086–1092. author disclosures ns has served on advisory boards, as a consultant, investigator, speaker, and/or other and has received honoraria and/or grants/research funding from almirall, actavis, allergan, anacor pharmaceuticals, auxilium pharmaceuticals, bausch health, bayer, biorasi, btg, carma laboratories, cassiopea, celgene corporation, cutera, cynosure, dusa pharmaceuticals, eclipse medical, eli lilly and company, endo international, endymed medical, ferndale laboratories, galderma, gerson lehrman group, hydropeptide, merz aesthetics, neostrata, novartis, nutraceutical wellness, palomar medical technologies, prescriber’s choice, regeneron, roche laboratories, samumed, solta medical, storz medical ag, suneva medical, vanda pharmaceuticals, and venus concept. fcb has served as consultant, speaker, investigator for galderma, leo pharma, almirall, cassiopea, ortho dermatologics, investigators encore, foamix, hovione, aclaris, cutanea. kb has received funding from allergan, galderma, evolus, and revance. zd received funding from ortho dermatologics to conduct the research presented in this poster. lk has acted as an investigator, advisor, speaker, and consultant for ortho dermatologics. et has served as speaker for novartis, ortho dermatologics, sun pharma, lilly, galderma, abbvie, and dermira; served as a consultant/clinical studies for hologic, ortho dermatologics, and galderma; and is a stockholder for accure. eg is an employee of ortho dermatologics and may hold stock and/or stock options in its parent company. • topical therapies are the first-line treatment for mild-to-moderate psoriasis or in combination with other therapies for severe disease.1 • compliance to topical therapies is a significant problem, with adherence rates of just 40-70%.2 • among other factors, it has been shown that patients’ attitudes toward both psoriasis and its treatment influence compliance.3 • the pso-insightful study was designed to assess patientreported factors that influence preference following once-daily topical treatment with cal/bd foam and gel. the saba questionnaire was developed with the aim to gain insight into how patients’ lives were impacted by psoriasis, and their attitudes to psoriasis and psoriasis treatments.4 results of subject’s assessment of behavior and attitudes (saba) survey toward psoriasis and treatments in the pso-insightful study all patients (n=212) age category, n (%) 18–39 years 48 (22.6) 40–59 years 92 (43.4) ≥60 years 72 (34.0) male:female, n (%) 133:79 (63:37) bmi, n (%) <25 kg/m2 37 (17.5) 25–30 kg/m2 73 (34.4) >30 kg/m2 102 (48.1) pga, n (%) mild 61 (28.8) moderate 122 (57.5) severe 29 (13.7) duration of psoriasis, n (%) <2 years 4 (1.9) 2–5 years 30 (14.2) >5 years 178 (84.0) bsa, n (%) <4% 93 (43.9) 4–6% 56 (26.4) 6–11% 38 (17.9) 11–15% 11 (5.2) ≥15% 14 (6.6) mpasi, n (%) 2–5 86 (40.6) 5.1–10 91 (42.9) >10 35 (16.5) mean dlqi 7.8 localized:widespread distribution of psoriasis, % 62:38 background • pso-insightful was a prospective, multicenter, phase iiib, open-label, randomized, two-arm crossover study including patients ≥18 years with mild-to-severe psoriasis of ≥6 months’ duration involving 2-30% bsa and mpasi of ≥2. [nct02310646] • after 4-week washout, 213 patients were randomized 1:1 to oncedaily cal/bd foam for 1 week, followed by cal/bd gel for 1 week, or vice-versa. • patients completed 6 questionnaires at different time periods evaluating patient preferences, one of which was a leo-created survey titled the subject’s assessment of behavior and attitudes (saba) questionnaire, following randomization. the saba questionnaire (13 questions) • 6 yes/no questions on “impact of psoriasis” • 7 questions on “attitudes to psoriasis and treatments” using a 5point scale (-2 to +2) • note: more detail on questionnaires available at clinicaltrials.gov. statistical analyses • full analysis set (fas) comprised all randomized patients who completed an on-study questionnaire (212 patients). results discussion table 1. patient demographics at baseline bmi, body mass index; bsa, body surface area; mpasi, modified psoriasis and severity index; pga, physician’s global assessment of disease severity impact of psoriasis yes, n (%) no, n (%) n/a, n (%) psoriasis impacts on my work 56 (26.4) 115 (54.2) 41 (19.3) psoriasis impacts on my social life 105 (49.5) 107 (50.5) 0 psoriasis impacts on my relationships/sex life 73 (34.8) 137 (65.2) 0 psoriasis has a physical impact on my life 85 (40.1) 127 (59.9) 0 psoriasis impacts on my self confidence 125 (59.0) 87 (41.0) 0 psoriasis impacts on my emotional well being 112 (53.1) 99 (46.9) 0 attitudes to psoriasis and treatments strongly/slightly agree, n (%) neither agree nor disagree, n (%) strongly/slightly disagree, n (%) i prefer my doctor to recommend the best treatment rather than offering me different options and letting me decide 159 (75.4) 18 (8.5) 34 (16.1) i regularly seek out information about psoriasis 145 (68.7) 27 (12.8) 39 (18.5) i am keen to try the newest treatments available 189 (90.0) 12 (5.7) 9 (4.3) being able to apply treatment quickly is very important to me 190 (90.1) 15 (7.1) 6 (2.8) i have a busy lifestyle that limits time for treatment 111 (52.6) 41 (19.4) 59 (28.0) i worry about the side effects of treatment 123 (58.2) 34 (16.1) 54 (25.6) i feel very self-conscious about psoriasis 134 (63.8) 33 (15.7) 43 (20.4) table 2. patient saba responses • pso-insightful was conducted in eu and canada; no us subjects participated in the study. • saba responses should be interpreted in the context of the pso-insightful study due to utilization of a leo-designed survey. • statistical analysis was not performed for responses to saba questionnaire; adjustments with baseline patient characteristics or treatment arm were not made. • no specific analyses of different responses based on patient characteristics (age, gender, severity of disease) was conducted. • fewer patients agreed with the statements “i have a busy lifestyle that limits time for treatment” (52.6%) and “i worry about the side effects of treatment” (58.2%) as compared to the majority of patients whom agreed with statements “being able to apply treatment very quickly is very important to me” (90.1%) and “i am keen to try the newest treatments available” (90.0%). • psychosocial impairment is highly heterogeneous across populations of psoriasis patients; the results of this survey only speak to the population in this study since the saba questionnaire is not a validated survey. • while these supplementary data provide insight into patient attitude and behavior toward psoriasis and treatments, more research is necessary to obtain a complete understanding of the data presented. references 1. nast a, gisondi p, ormerod ad, et al. european s3-guidelines on the systemic treatment of psoriasis vulgaris--update 2015--short version--edf in cooperation with eadv and ipc. j eur acad dermatol venereol 2015;29:2277–94. 2. devaux s, castela a, archier e, et al. adherence to topical treatment in psoriasis: a systematic literature review. j eur acad dermatol venereol 2012;26(suppl 3):61–67. 3. feldman sr, horn ej, balkrishnan r, et al. psoriasis: improving adherence to topical therapy. j am acad dermatol 2008;59(6);1009-1016. 4. hong c-h, papp ka, lophaven kw, et al. patients with psoriasis have different preferences for topical therapy, highlighting the importance of individualized treatment approaches: randomized phase iiib pso-insightful study [submitted]. douglas diruggiero, mhs, pa-c1; chih-ho hong, md2; lisa tiu, pharmd3; scott freeman, pa-c4 figure 1. pso-insightful study design conclusion • results from the saba questionnaire in the pso-insightful study show that fewer patients reported psoriasis impacts interpersonal relationships (work and sex life), while more than half of patients reported psoriasis has a personal impact on their lives (self confidence and emotional wellbeing). • overall, saba responses indicate patients’ attitudes toward specific aspects of psoriasis treatment (i.e., quick treatment application, willingness to try newest treatments) are stronger than their worry of side effects or selfperception of lifestyles that limit time for treatment. • while these supplementary data provide insight into patient attitude and behavior toward psoriasis and treatments, more research is necessary to obtain a complete understanding of the data presented. impact of psoriasis • about half of patients reported that psoriasis has an impact on self confidence (59.0%), emotional well being (53.1%), and social life (49.5%). • responses indicate that psoriasis also impacts work (26.4%), relationships/sex life (34.8%), and physical aspects (40.1%) of the lives of surveyed individuals. attitudes to psoriasis and treatments • more patients preferred that their doctors recommend the best treatment rather than being offered different options (75.4%) and/or regularly seek out information about psoriasis (68.7%). • majority of patients agreed with the statements “being able to apply treatment very quickly is very important to me” (90.1%) and “i am keen to try the newest treatments available” (90.0%). • approximately half of patients agreed with the statements “i have a busy lifestyle that limits time for treatment” (52.6%) and “i worry about the side effects of treatment” (58.2%). • more patients reported that they feel self-conscious about psoriasis (63.8%) than not (20.4%). methods limitations acknowledgements: funding for research provided by leo pharma a/s. editorial support provided by leo pharma inc. poster originally presented at maui derm np+pa summer 2017; june 14-17, 2017; colorado springs, co. 1rome dermatology center, rome, ga; 2university of british columbia, department of dermatology and skin science and probity medical research, surrey, canada; 3leo pharma inc., madison, nj; 4advanced dermatology, st. petersburg, fl fc17posterleodiruggieroresultsofbehaviorassessment.pdf skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 747 skinmages successful treatment of morphea with topical ruxolitinib mckenzie a. dirr, ba, bs1, avi bitterman, md2, roudha al-dehneem, md, msc2, alice b. gottlieb md, phd2 1 medical university of south carolina, charleston, sc 2 icahn school of medicine at mount sinai, new york, ny figure 1. right shoulder hyperpigmentation before (left) and after (right) 3 months of topical ruxolitinib 1.5% cream. a 50-year-old female, fitzpatrick skin type v, presented to the dermatology clinic with several areas of hyperpigmentation and skin thickening. while asymptomatic, the lesions were of concern to the patient and a workup was initiated. physical exam revealed several indurated, ill-defined hyperpigmented plaques on the right upper shoulder, left upper back, and right chest (figure 1). laboratory workup was negative for autoimmune antibodies, including antinuclear antibodies, scl 70 anti-centromere antibodies, and anti-rna polymerase i/iii antibodies. a biopsy of the lesions showed thickened, homogenized dermis replaced by an acellular fibrosis with diminution of adnexae. given the clinicopathologic correlation, the patient was diagnosed with morphea and was counseled on the risks and benefits of available treatments. she ultimately decided against systemic therapy due to her un-vaccinated status against covid-19. topical clobetasol was initiated but discontinued due to localized cutaneous atrophy. further conventional treatment introduction skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 748 options were trialed with unsatisfactory response, including topical and intralesional triamcinolone and topical tacrolimus. due to the lack of improvement, the patient was initiated on topical ruxolitinib 1.5% bid, and at her 3-month follow up visit, physical exam revealed lightened hyperpigmentation in affected areas with improvements in texture (figure 2). the patient was pleased with the response, and she was counseled to continue to use topical ruxolitinib. morphea, also known as localized scleroderma, is thought to arise due to activation of the immune system.1,2 the autoimmune nature of the disease causes inflammation and subsequent hyperactivation of fibroblasts with resultant collagen deposition and fibrosis.1,2 elevated inflammatory cytokines, including il-2 and il6, could play a role disease pathogenesis.3 morphea typically presents with sclerotic, firm and fibrotic plaques or patches of cutaneous hyperpigmentation.1 lesions can be active, presenting as erythematous lesions with central dyspigmentation surrounded by a violaceous border, or inactive, presenting as hyperpigmented lesions with sclerosis in the central lesion. 1 there are many variants of morphea, most commonly presenting as circumscribed or, more rarely, generalized.1 while there is no gold-standard therapy, firstline treatment for circumscribed or generalized morphea typically consists of a topical corticosteroid, tacrolimus, or phototherapy.1,2 our case highlights an interesting response to topical ruxolitinib, which is not historically used for morphea treatment. ruxolitinib is a janus-kinase (jak) 1 and 2 inhibitor with anti-inflammatory properties.4,5 ruxolitinib works by blocking the receptor-associated protein kinases jak1 and jak2, inhibiting the jak-stat pathway.4,5 when jak1 and jak2 are active, this pathway produces inflammatory cytokines and hematopoiesis.4,5 ruxolitinib blocks this mechanism, downregulating the production of pro-inflammatory cytokines, such as il-2 and il-6, and thus decreasing the damaging effects of inflammation.4,5 interestingly, ruxolitinib has been found to be efficacious in other inflammatory processes, including atopic dermatitis and psoriasis.4 we suspect the positive response seen in our patient may be due to the anti-inflammatory effects of ruxolitinib, which may have blocked the immune activation, cytokine release, and residual fibrosis seen in morphea.1 our case highlights a potential safe and effective therapeutic alternative for the treatment of morphea, which may inform future clinical considerations for patients unable to tolerate or respond to traditional therapies. conflict of interest disclosures: none funding: none corresponding author: mckenzie a. dirr, ba, bs medical university of south carolina 96 jonathan lucas street suite 601, msc 617 charleston, sc 29425 phone: (843) 792-2081 email: dirr@musc.edu references: 1. bolognia j, schaffer jv, duncan ko, ko cj. dermatology essentials. second edition. elsevier; 2022. 2. albuquerque jv, andriolo bn, vasconcellos mr, civile vt, lyddiatt a, trevisani vf. interventions for morphea. cochrane database syst rev. 2019;7(7):cd005027. published 2019 jul 16. doi:10.1002/14651858.cd005027.pub5 3. kurzinski k, torok ks. cytokine profiles in localized scleroderma and relationship to clinical features. cytokine. 2011;55(2):157164. doi:10.1016/j.cyto.2011.04.001 4. traidl s, freimooser s, werfel t. janus kinase inhibitors for the therapy of atopic dermatitis. allergol select. 2021 aug skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 749 27;5:293-304. doi: 10.5414/alx02272e. pmid: 34532638; pmcid: pmc8439108. 5. elli em, baratè c, mendicino f, palandri f, palumbo ga. mechanisms underlying the anti-inflammatory and immunosuppressive activity of ruxolitinib. front oncol. 2019 nov 7;9:1186. doi: 10.3389/fonc.2019.01186. pmid: 31788449; pmcid: pmc6854013. skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 246 brief article hydroxychloroquine and acute generalized exanthematous pustolosis justine galambus, bs1, atefah vafa, md2 1 morsani college of medicine, university of south florida, tampa, fl 2 department of rheumatology, university of south florida, tampa, fl acute generalized exanthematous pustulosis (agep) is a rare, potentially lethal, cutaneous reaction precipitated by drugs in more than 90% of cases,1 with the most common triggers being pristinamycin, aminopenicillins, quinolones, (hydroxy)chloroquine, sulfonamides, terbinafine, and diltiazem.1 agep typically presents within one day of treatment after antibiotic exposure versus eleven days after other drugs, including hydroxychloroquine (hcq, plaquenil).1 agep presents with innumerable pinhead-sized pustules arising on a diffuse erythematous background and are reported to localize in intertriginous zones, the trunk, and upper extremities.2 diagnostic criteria outside of a pustular eruption include a fever, neutrophilia with or without mild eosinophilia, subcorneal or intraepidermal pustules on skin biopsy, and spontaneous resolution in less than 15 days.1 sidoroff et al developed a validation scale founded in these criteria to aid clinicians in the diagnosis of agep. the first step in drug-induced agep treatment is withdrawal of the culprit drug.3 though spontaneous resolution without intervention is reported,4 first-line therapy is steroids, recurrent or refractory cases can be treated with cyclosporin,5 etretinate,6 or dapsone7. though the reaction can be very disconcerting and uncomfortable for the patient, the general prognosis is good with the overall mortality rate of up to 5%;2 those with the highest risk have comorbidities.8 hcq is an antimalarial medication that is frequently used as an immunosuppressive. hcq-precipitated agep is predominantly reported in the context of hcq’s immunosuppressive action, most commonly when used to treat rheumatoid arthritis,9 sjogren’s syndrome,5 and systemic lupus erythematous.6 however, with the increased use of hcq as an antiviral for treatment of covid-19, several cases of agep have been reported.10 agep tends to affect women, and hcq-precipitated agep abstract acute generalized exanthematous pustulosis (agep) is a rare, potentially lethal, cutaneous reaction most commonly precipitated by drugs. removal of the offending drug or treatment of the underlying infection usually results in recovery, though corticosteroids are often used to bolster treatment. we report a case of hydroxychloroquine-induced agep in an adult female. though removal of hydroxychloroquine (hcq) did largely resolve her rash, she continued to require corticosteroids over 200 days after she first began taking hcq. introduction skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 247 certainly follows that pattern as evidenced by this literature review. however, this can, at least in part, be attributed to the common indications for hcq predominantly affecting women. the overall incidence rate of agep is between 1 to 5 cases per million per year based on the euroscar study, however, this is reported with the caveat that reliable data is missing.1 the prevalence of hcqprecipitated agep has not been studied. hcq-precipitated agep is associated with a delayed onset as well as recalcitrant course, leading to the proposal of a new classification, generalized pustular figurate erythema (gpfe).7 gpfe presents as a sudden eruption of pruritic, erythematous papules on the face, with concurrent fever and neutrophilic leukocytosis. there have only been two reports of death following hcq-precipitated agep; however, both were covid-19 patients who died following covid19-attributed pulmonary emboli. a 38-year old african america female with a prior history of eczema presented with a diffuse desquamating rash with a prior medical history of recently diagnosed systemic lupus erythematous (sle), arthritis, intermittent parotid swelling and dry mouth, and previous pustular palmar rashes. the patient was originally prescribed hydroxychloroquine 200 mg bid for treatment of her sle. an antibody panel revealed elevated anti-nuclear antibodies, anti-ssa and anti-ssb antibodies. rheumatoid factor, anti-dsdna antibodies, anti-smith antibodies, and anti-scl-70 antibodies were negative. biopsy showed a spongiotic epidermis with hyperkeratosis, variable loss of the granular layer, and scattered corneal pustules. the dermis has a mild inflammatory neutrophilic infiltrate with scattered eosinophils. gram staining, gms (gomori methenamine silver, used to detect fungi) and pas (periodic acid-schiff, also can be used to detect fungi) stains were negative. immunofluorescence for igg, iga, igm, c3, fibrin, and albumin were also negative. the biopsy findings were consistent with agep and ruled out sjs/ten. approximately two weeks after beginning hcq, the patient noted a diffuse rash covering her body; she did not note where the rash began. upon admission, she was found to be afebrile with a rash on the trunk and bilaterally on the upper and lower extremities, sparing mucosal sites. hcq was stopped owing to suspected drug reaction, and after four days, the patient was discharged with prednisone. prior to discharge, the patient developed urticarial lesions around her eyes that were determined not to be related to agep. following discharge and hcq discontinuation, she had worsening periorbital urticaria and swelling, as well as worsening pruritic, painful desquamating rash with rash on her upper extremities. she eventually began experiencing some relief with continued prednisone. approximately six months after initial admission, the patient rash was noted to have new pustular rashes over the wrists, abdomen, and face. her subsequent disease course and treatment is summarized in figure 1. hydroxychloroquine is associated with a distinct form of agep, prompting consideration of a distinct classification. typical agep diagnostic criteria include of a pustular eruption, fever, neutrophilia with or without mild eosinophilia, subcorneal or intraepidermal pustules on skin biopsy, and spontaneous resolution in less than 15 case report discussion skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 248 figure 1. timeline showing the disease course of the patient’s hydroxychloroquine-induced agep days.1 the patient here presented with a pustular eruption with neutrophilia, mild eosinophilia, and intraepidermal pustules on biopsy. however, the patient was notably afebrile, and resolution was not achieved by day 30. it is unclear when the patient experienced initial full resolution of her rash. hydroxychloroquine is notable for a long half-life, approximately 40-50 days.11 it takes approximately 5-6 half-lives to significantly eliminate a drug, meaning that it could take upwards of 200 days in order to clear hcq. this could explain why agep is notably recalcitrant and can last longer than the typical 15-day resolution when secondary to hcq use. though hcq-induced agep can have spontaneous resolution, prednisolone or prednisone is often used to ease symptoms as with this patient. prednisone was noted to have the dual benefit of aiding with the patient’s arthritis as well. while this was not the case for this patient, of note is the use of hcq in treatment of covid-19. though no longer recommended,12 some physicians and patients may be inclined to pursue hcq as treatment for covid-19. though the deaths following hcq-induced agep were attributed to pulmonary emboli, it is important for patients to understand agep as a potentially severe side effect. in particular, the longer course and pain associated with the rash may significantly impact patient well-being long after potential covid-19 resolution. therefore, this should be discussed as part of an informed consent with patients who desire treatment with hcq. conflict of interest disclosures: none funding: none corresponding author: justine galambus, bs morsani college of medicine university of south florida 560 channelside dr tampa, fl 33602, usa email: galambus@usf.edu references: 1. sidoroff a, dunant a, viboud c, et al. risk factors for acute generalized exanthematous pustulosis (agep)-results of a multinational case-control study (euroscar). case control study. br j dermatol. nov 2007;157(5):989-96. doi:10.1111/j.1365-2133.2007.08156.x 2. roujeau jc. clinical heterogeneity of drug hypersensitivity. review. toxicology. apr 15 2005;209(2):123-9. doi:10.1016/j.tox.2004.12.022 3. hoetzenecker w, nägeli m, mehra et, et al. adverse cutaneous drug eruptions: current understanding. review. semin immunopathol. jan 2016;38(1):75-86. doi:10.1007/s00281-0150540-2 4. evans cc, bergstresser pr. acute generalized exanthematous pustulosis precipitated by hydroxychloroquine. case report. j am acad dermatol. apr 2004;50(4):650-1. doi:10.1016/s0190-9622(03)02733-6 conclusion skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 249 5. castner nb, harris jc, motaparthi k. cyclosporine for corticosteroid-refractory acute generalized exanthematous pustulosis due to hydroxychloroquine. case report. dermatol ther. sep 2018;31(5):e12660. doi:10.1111/dth.12660 6. matsuda-hirose h, sho y, yamate t, et al. acute generalized exanthematous pustulosis induced by hydroxychloroquine successfully treated with etretinate. case report. j dermatol. feb 2020;47(2):e53-e54. doi:10.1111/13468138.15185 7. schwartz ra, janniger ck. generalized pustular figurate erythema: a newly delineated severe cutaneous drug reaction linked with hydroxychloroquine. article. dermatol ther. may 2020;33(3):e13380. doi:10.1111/dth.13380 8. szatkowski j, schwartz ra. acute generalized exanthematous pustulosis (agep): a review and update. review. j am acad dermatol. nov 2015;73(5):843-8. doi:10.1016/j.jaad.2015.07.017 9. pearson kc, morrell ds, runge sr, jolly p. prolonged pustular eruption from hydroxychloroquine: an unusual case of acute generalized exanthematous pustulosis. case report. cutis. mar 2016;97(3):212-6. 10. delaleu j, deniau b, battistella m, et al. acute generalized exanthematous pustulosis induced by hydroxychloroquine prescribed for covid-19. case report. j allergy clin immunol pract. jun 7 2020;doi:10.1016/j.jaip.2020.05.046 11. schrezenmeier e, dörner t. mechanisms of action of hydroxychloroquine and chloroquine: implications for rheumatology. nat rev rheumatol. mar 2020;16(3):155-166. doi:10.1038/s41584-020-0372-x 12. elavarasi a, prasad m, seth t, et al. chloroquine and hydroxychloroquine for the treatment of covid-19: a systematic review and metaanalysis. j gen intern med. nov 2020;35(11):3308-3314. doi:10.1007/s11606020-06146-w ex-vivo determination of antifungal activity of a new prescription non steroidal facial cream against malassezia furfur in human skin explants fall clinical dermatology conference® october 12-15, 2017. las vegas, nevada, usa introduction malassezia furfur (mf) is a lipophilic (lipid-dependent) fungus that is part of normal human skin flora that grow on the sebaceous areas of human skin, including the face, scalp, and upper trunk. although part of the normal human skin flora, uncontrolled mf proliferation in some patients leads to development of skin diseases including tinea versicolor, pityrosporum folliculitis, and seborrheic dermatitis (sd). the objective of this study was to examine the anti-fungal properties of a new non-steroidal facial cream (nsfc) in human organotypic skin cultures (hoscs) inoculated with mf in an ex-vivo model. this model was developed to mimic sd conditions in order to evaluate the antifungal properties of an nsfc product containing zinc pca, piroctone olamine, dihydroavenanthramide, biosaccharide gum-2 and stearyl glycyrrhetinate. mf suspension was placed on the skin surface and incubated for 24 hours under conditions that are optimal for mf growth. 24 hours post initial mf inoculation, nsfc was topically applied on skin explants (2 mg/cm2). on control skin explants, inoculated in the same way, no product was applied. a sham control group was treated with a neutral cream without known antifungal properties. growth of mf was monitored by quantifying mf colony forming units (cfus) in a sample removed from skin surface. the quantification of cfus was carried out by recovering fungal microorganisms from skin explants and subsequent plating them following the serial dilution method to determine the number of cfus (figure 2). results in the altered skin explants, inoculation with mf led to successful colonization as indicated by the significant increase in mf cfus compared to baseline: a 2-fold increase at 24 hours. the topical application of nsfc significantly reduced (p<0.05) the number of mf cfus by 90% compared to the untreated control group. the sham control treated with neutral cream did not lead to a significant reduction of the mf population (15% decrease in cfus) (figure 3). isdin s.a.provencals, 33 barcelona spain m. furfur quantification c .f .u . 3000000 2500000 2000000 1500000 1000000 500000 0 control 0c.f.u m.furfur 1635000 nsfc vaseline 152800 1560000 figura 1. skin samples images stained with violet crystal. a) control b) m.furfur c) m. furfur + nsfc d) m. furfur + vaseline figura 3. m. furfur population and response to nsfc application. significant decrease in m. furfur colonies in skin treated with nsfc. (*)=p<0.05 negative control. no m. furfur no nfsc (5 skin replicates) figura 2. study design ex-vivo model with human skin. nsfc: non-steroidal facial cream partial tape striping skin samples without m. furfur no product application 48h 24h m.furfur cfu & picture 24h malassezia inoculation with no nsfc (5 skin replicates) partial tape striping malassezia furfur incubation (106 ufc) no product application 48h 24h m.furfur cfu & picture 24h malassezia inoculation with nsfc (5 skin replicates) partial tape striping malassezia furfur incubation (106 ufc) nsfc 48h 24h m.furfur cfu & picture 24h malassezia inoculation with vaseline (5 skin replicates) partial tape striping malassezia furfur incubation (106 ufc) vaseline application 48h 24h m.furfur cfu & picture 24h a b c d * methods human organotypic skin cultures hoscs were obtained from abdominal skin removed during cosmetic surgery. the explants were altered by partial elimination of stratum corneum to facilitate colonization and stabilization of the mf (figure 1). conclusions in this ex-vivo model, the topical application of a new nsfc significantly reduced the mf cfu count. these findings demonstrate the antifungal properties of this nsfc, specifically for mf, a key contributing fungus in seborrheic dermatitis. referencias: 1.gupta ak., et al. seborrheic dermatitis of the scalp: etiology and treatment. j drugs dermatol. 2004;3(2):155-8. 2.barac a., et al. presence, species distribution, and density of malassezia yeast in patients with seborrhoeicdermatitis a community-based case-control study and review of literature. mycoses. 2015;58(2):69-75. 3.tajima m., et al. molecular analysis of malassezia microflora in seborrheic dermatitis patients: comparison with other diseases and healthy subjects. j invest dermatol. 2008 feb;128(2):345-51. epub 2007 aug 2. granger c.1, goñi-de-cerio f.2, martínez-masana g.1, garre a1. 1. innovation and development, isdin s.a. barcelona, spain. 2. gaiker-ik4 technology centre. parque tecnológico ed 202, zamudio, vizcaya, spain. fc17posterisdinexvivogranger.pdf powerpoint presentation 3 years of tralokinumab treatment provides long-term disease control as demonstrated by clinically meaningful outcomes in moderate-to-severe atopic dermatitis richard b warren1, kristian reich2, eric simpson3, richard langley4, antonio costanzo5, hidehisa saeki6, peter almgren7, emilia vacko7, anna carlsson7, melinda gooderham8, mette deleuran9, juan francisco silvestre10, stefan weidinger11, andrew blauvelt12 1dermatology centre, salford royal nhs foundation trust and nihr biomedical research centre, the university of manchester, manchester, uk; 2translational research in inflammatory skin diseases, institute for health services research in dermatology and nursing, university medical center hamburg-eppendorf, hamburg, germany; 3department of dermatology, oregon health & science university, portland, or, usa; 4division of clinical dermatology and cutaneous science, dalhousie university, halifax, nova scotia, canada; 5dermatology unit department of biomedical sciences, humanitas university, milano, italy; skin pathology laboratory, humanitas research hospital irccs, milano, italy; 6department of dermatology, nippon medical school, tokyo, japan; 7leo pharma a/s, ballerup, denmark; 8skin centre for dermatology, peterborough, on, canada; department of dermatology, queen's university, kingston, on, canada; probity medical research, waterloo, on, canada; 9department of dermatology, aarhus university hospital, aarhus, denmark; 10dermatology department, hospital general universitario de alicante, alicante, spain; 11department of dermatology and allergy, university hospital schleswig-holstein, campus kiel, kiel, germany; 12oregon medical research center, portland, or, usa ecztend interim efficacy analysis set n=347 age median years (iqr) 42.0 (30.0; 53.0) sex n (%) male female 205 (59.1) 142 (40.9) race n (%)a white black asian 259 (74.6) 20 (5.8) 56 (16.1) parent trial n (%) ecztra 1 ecztra 2 224 (64.6) 123 (35.4) age at onset of ad median years (iqr) 3.0 (1.0; 15.0) duration of ad median years (iqr) 29.0 (19.0; 43.0) parent trial baseline ecztend baseline iga severity n (%) clear/minimal (score=0/1) mild (score=2) moderate (score=3) severe (score=4) 172 (49.6) 175 (50.4) 98 (28.2) 123 (35.4) 106 (30.5) 20 (5.8) easi median (iqr) 26.7 (19.7; 38.4) 4.7 (2.2; 12.4) scorad median (iqr) 68.1 (60.8; 78.1) 32.8 (20.6; 46.9) dlqi median (iqr), n 17.0 (11.0; 23.0), n=343 5.0 (2.0; 10.0), n=332 worst weekly pruritus nrsa median (iqr), n 7.9 (6.9; 8.9), n=346 5.0 (3.0; 8.0), n=347 table 1. baseline demographic and disease characteristics of patients with 3 years total tralokinumab treatment (ecztend interim efficacy analysis set) table 2. summary of adverse events (aes) in patients with 3 years total tralokinumab treatment ain pts, worst pruritus nrs was assessed daily; in ecztend, worst pruritus nrs was assessed based on recall of the previous week before the visit. conclusions • clinically meaningful improvements were observed in ad signs and symptoms in patients with moderate-to-severe ad treated with tralokinumab for 3 years • nine out of ten patients achieved at least one of the clinically relevant outcomes of easi ≤ 7, itch nrs ≤ 4, or dlqi ≤ 5, representing mild/no ad; approximately 60% achieved clinically meaningful outcomes by all three measures • the response rates were maintained over time with patients having easi ≤ 7 for more than 80% of visits during the 3 years of treatment • these data, in combination with the favorable safety profile, suggest tralokinumab as an efficacious and well-tolerated treatment option for long-term disease control in patients with moderate-tosevere ad aincludes 347 patients from the pts ecztra 1 and 2 who had consistently received tralokinumab for a total of 3 years at data cutoff, april 30, 2021. bincludes patients from a pooled safety analysis set from parent trials ecztra 1, 2, 3, 5, and phase 2b, previously presented at rad virtual 20201; aes related to study drug and aes leading to withdrawal during initial treatment sourced from data on file; tcs rules varied across parent trials with mandatory tcs in ecztra 3, and tcs use not part of treatment regimen in ecztra 1, ecztra 2, and ecztra 5. crate calculated by number of patients divided by pye until first event, multiplied by 100. drate calculated by number of events divided by pye, multiplied by 100. efor pts, cochran-mantel-haenszel weights were applied to calculate adjusted ae incidences and rates to account for different randomization ratios across pts.7 faes related to study drug comprise aes considered possibly or probably related by the investigator and aes with missing causality. objective to evaluate the efficacy and safety of 3 years of tralokinumab treatment, using clinically relevant outcomes indicating disease control, for adults with moderate-to-severe ad materials and methods patients and treatment • in ecztend, patients who completed pt of tralokinumab received open-label tralokinumab 300 mg every two weeks (q2w, home use) plus optional topical corticosteroids (tcs, us class ≥4 or europe class ≤3) or topical calcineurin inhibitor (tci), with visits every 8 weeks o for key inclusion and exclusion criteria, please see blauvelt et al5 o multiple tralokinumab pt of varying duration will contribute to the ecztend population (ecztra 1-8 and the investigator-initiated study traski, conducted in 11 countries) o while ecztra 3-5 and 7 were completed at data cutoff (april 30, 2021), participants in these trials did not receive 52 weeks of tralokinumab and therefore were not included in the 3-year efficacy analysis set • this post hoc analysis assessed tralokinumab efficacy in a homogenous group of participants with the longest tralokinumab treatment duration at data cutoff (april 30, 2021) o data are presented from eligible adult patients with moderate-to-severe ad who completed 3 years of tralokinumab treatment irrespective of response in the pt ecztra 1 and 2 (1 year in pt, 2 years in ecztend; figure 1; n=347 of 1442 total enrolled in ecztend at data cutoff) analyses • efficacy outcomes assessed were: o proportion of patients with 3 years total tralokinumab treatment achieving easi-75/90, iga 0/1, and easi ≤ 7 o percentage of patients achieving mild or no disease, defined as easi ≤ 7, itch nrs ≤ 4, or dlqi ≤ 5, after 3 years of tralokinumab treatment o proportion of time with mild/no disease during 3 years total tralokinumab treatment • for easi-75/90 and iga 0/1 response rates, as observed data are presented, and intermittent missing data are presented using last observation carried forward (locf). modified non-responder imputation (mnri) sets discontinuation from ecztend due to adverse event(s) or lack of efficacy as non-response and uses locf for other missing data results baseline demographics and characteristics • this post hoc analysis included 347 patients from the pts ecztra 1 and 2 who had entered ecztend and consistently received tralokinumab for a total of 3 years at data cutoff, april 30, 2021 (fig. 1b, table 1) • amongst patients who completed 3 years of tralokinumab treatment (n=347), median easi improved from 26.7 (iqr 19.7; 38.4) at pt baseline to 3.0 (iqr 1.0; 6.7) after one year of pt sustained improvement in lesion extent and severity with continued tralokinumab • amongst patients who completed 3 years of tralokinumab treatment at data cutoff, o easi-75 and easi-90 were achieved in 76% (263/347) and 54% (186/347) of patients by mnri, respectively (figure 2) o iga 0/1 was achieved in 44% (151/347) by mnri (figure 2) o easi ≤7 was achieved by 75% (261/347) by mnri (figure 2) figure 2. proportion of patients with 3 years total tralokinumab treatment achieving easi-75, easi-90, iga 0/1, and easi ≤7 aas observed, includes patients from the pts ecztra 1 and 2 who had consistently received tralokinumab for a total of 3 years at data cutoff, april 30, 2021. bintermittent missing data imputed using locf. cdiscontinuation from ecztend due to adverse event(s) or lack of efficacy set as non-response, other missing imputed with locf. scan to download a copy of this poster copies of this poster and its content, obtained through this qr code, are for personal use only and may not be reproduced without written permission from the authors introduction • atopic dermatitis (ad) is a chronic skin disease which may impact patients throughout their lifespan, requiring efficacious long-term treatment options with a favorable safety profile1 • the european guidelines (euroguiderm) define disease control or remission as satisfactory reduction of the signs and symptoms of ad whilst being on a safe long-term anti-inflammatory treatment2 o an international consensus previously defined a set of core decision points for systemic therapies at 6 months, including easi ≤ 7, itch nrs ≤ 4 and dlqi ≤ 5 representing mild/no disease3 • tralokinumab, a specific, high-affinity interleukin-13 inhibitor, is approved in europe, canada, and the united states for the treatment of adults with moderate-to-severe ad • ecztend (nct03587805) is an ongoing open-label extension trial assessing the safety and efficacy of tralokinumab over 5 years after the completion of parent trials (pt) o a recently presented interim safety analysis of adult patients with up to 42 months of exposure confirmed the safety profile of tralokinumab4 maintained improvements in clinically relevant outcomes at 3 years of tralokinumab treatment • patients were controlled (mild/no disease) for the majority of the 3 years of tralokinumab treatment (figure 3) • at 3 years of tralokinumab treatment, 93% (254/274, as observed) of patients achieved at least one outcome (figure 4) • median duration of response during pt and ecztend up to week 104, as observed: o >80% of visits with easi ≤ 7 response [84.7 (q1,q3; 55.8, 93.8)%] o >80% of visits with dlqi ≤ 5 [84.1 (43.1, 96.9)%] o >70% of visits with itch nrs ≤ 4 [73.8 (31.7, 91.3)%] • using mnri, 84% of patients achieved at least one clinically meaningful improvement, and 51% achieved clinically meaningful improvements of all three measures 93% (254/274) of patients achieved at least one outcome on tralokinumab figure 4. percentage of patients achieving mild or no disease by at least one outcome after 3 years of tralokinumab treatment 9% dlqi ≤5 n/n 206/270 12% 6% easi ≤7 n/n 227/274 itch nrs ≤4 n/n 188/273 3% 4% 3% 58% data as observed. denominator is the smallest number of patients with dlqi, easi, and itch nrs measurement(s) in category, except for individuals with no response where largest number is used. no response includes non-evaluable patients, e.g., for category dlqi≤5 + easi≤7 where dlqi is not measured for one or more patient(s). no new safety signals with continued tralokinumab treatment • the safety profile was consistent with the pts6 and the overall ecztend population (n=1442),4 with no new safety signals arising with continued tralokinumab (table 2) aes in ecztend ecztend interim efficacy analysis seta aes up to week 16 in parent trials initial tralokinumab treatmentb tralokinumab q2w + optional tcs (n=347; pye=707.7) tralokinumab q2w ± tcs (n=1605; pye=473.2) placebo q2w ± tcs (n=680; pye=193.1) n (%) ratec [(np/pye)*10 0] e rated [(ne/pye)*10 0] n (adj. %)d e adj. rated,e [(ne/pye)*10 0] n (adj. %)d e adj. rated,e [(ne/pye)*10 0] all aes 295 (85.0) 144.2 1422 200.9 1080 (65.7) 3148 639.5 449 (67.2) 1276 678.3 aes related to study drugf 102 (29.4) 18.3 251 35.5 463 (28.0) 1025 207.6 176 (26.8) 365 195.6 severity mild 247 (71.2) 80.5 917 129.6 881 (53.2) 2127 429.8 326 (49.0) 738 391.0 moderate 180 (51.9) 40.6 450 63.6 518 (31.5) 917 189.5 258 (39.0) 478 254.3 severe 31 (8.9) 4.6 55 7.8 77 (4.6) 104 20.2 40 (6.3) 60 33.0 serious aes 31 (8.9) 4.6 34 4.8 37 (2.1) 38 7.4 18 (2.8) 22 11.9 leading to withdrawal from trial 9 (2.6) 1.3 9 1.3 34 (2.0) 42 8.6 12 (1.8) 15 8.0 references 1. weidinger s, novak n. lancet. 2016;387(10023):1109-1122. 2. wollenberg a, et al. j eur acad dermatol venereol. 2022;36(9):1409-1431. 3. de bruin-weller m, et al. acta derm venereol 2021; 101: adv00402. 4. blauvelt a, et al. poster presented at: american academy of dermatology annual meeting; march 25-29, 2022, boston, ma. 5. blauvelt a, et al. j am acad dermatol. 2022;s0190-9622(22)02345-3. 6. simpson e, et al. poster presented at: revolutionizing atopic dermatitis (rad) conference; december 13–14, 2020, virtual. 7. chuang-stein c. pharm stat 2011; 10:3–7. disclosures richard b warren has received research grants or consulting fees from abbvie, almirall, amgen, arena, astellas, avillion, boehringer ingelheim, bristol myers squibb, celgene, dice, eli lilly, gsk, janssen, leo pharma, medac, novartis, pfizer, sanofi, sun pharma, ucb, and union. he is supported by the manchester nihr biomedical research centre. kristian reich has served as advisor and/or paid speaker for and/or participated in clinical trials sponsored by abbvie, almirall, amgen, boehringer ingelheim, bristol-myers squibb, celgene, forward pharma, gilead, galderma, janssen-cilag, kyowa kirin, leo, lilly, medac, novartis, ocean pharma, pfizer, sanofi, ucb. kristian reich is co-founder of moonlake immunotherapeutics. eric simpson reports grants and/or personal fees from abbvie, boehringer ingelheim, celgene, dermavant, dermira, eli lilly, fortébio, galderma, incyte, kyowa kirin, leo pharma, medimmune, menlo therapeutics, merck, novartis, ortho dermatologics, pfizer, pierre fabre dermo cosmetique, regeneron, sanofi, tioga, and valeant. richard langley has served and received compensation in the form of grants and/or honoraria as principal investigator for and is on the scientific advisory board or has served as a speaker for abbvie, amgen, boehringer ingelheim, celgene, eli lilly, janssen, leo pharma, merck, novartis, pfizer, and ucb. antonio costanzo has received research grants or consulting fees from abbvie, almirall, amgen, boehringer ingelheim, bristol myers squibb, celgene, eli lilly, janssen, leo pharma, novartis, pfizer, sanofi, ucb. hidehisa saeki has received lecture fees from kyorin, kyowa kirin, leo pharma, mitsubishi tanabe, maruho, sanofi, tokiwa, and taiho; and scholarship donations from esai, mitsubishi tanabe, maruho, and torii. peter almgren, emilia vacko, and anna carlsson are employees of leo pharma. melinda gooderham has been an investigator, speaker and/or advisor for: abbvie, amgen, akros, anaptysbio, aslan, arcutis, bausch health, bms, boehringer ingelheim, celgene, dermira, dermavant, eli lilly, galderma, gsk, incyte, janssen, kyowa kirin, leo pharma, medimmune, merck, novartis, pfizer, regeneron, roche, sanofi genzyme, sun pharma, and ucb. mette deleuran has received research support, honoraria for lecturing, and/or is on consulting/advisory board agreements with abbvie, arena pharmaceuticals, aslan pharmaceuticals, incyte, la roche posay, leo pharma, lilly, pfizer, pierre fabre, regeneron, and sanofi genzyme. juan francisco silvestre has served as a consultant and received speaking fees at educational events for sanofi-genzyme, regeneron, abbvie, leo pharma, and novartis and has served as the principal investigator in clinical trials sponsored by abbvie, amgen, astrazeneca, bms, galderma, incyte, leo pharma, lilly, novartis, and pfizer. stephan weidinger has received institutional research grants from sanofi deutschland gmbh, leo pharma, and la roche posay, has performed consultancies for sanofi-genzyme, regeneron, leo pharma, abbvie, pfizer, eli lilly, kymab, and almirall, he has also lectured at educational events sponsored by sanofi-genzyme, regeneron, leo pharma, abbvie, and eli lilly, and is involved in performing clinical trials with many pharmaceutical industries that manufacture drugs used for the treatment of psoriasis and atopic dermatitis. andrew blauvelt has served as a speaker, scientific adviser, and / or clinical study investigator for abbvie, abcentra, aligos, almirall, amgen, arcutis, arena, aslan, athenex, boehringer ingelheim, bristol-myers squibb, dermavant, ecor1, eli lilly, evommune, forte, galderma, incyte, janssen, landos, leo pharma, novartis, pfizer, rapt, regeneron, sanofi genzyme, sun pharma, ucb pharma, vibliome, and xencor acknowledgements this analysis was sponsored by leo pharma a/s. medical writing and editorial support from alphabet health by meredith whitaker, phd and juliel espinosa, phd was funded leo pharma a/s, ballerup, denmark, according to good publication practice guidelines (https://www.ismpp.org/gpp3). richard b warren is supported by the manchester nihr biomedical research centre. this work was previously presented at eadv 2022. abbreviations %, percentage of patients with ≥1 event; adj., adjusted (for pts, cochran-mantel-haenszel weights were applied to calculate adjusted ae incidences and rates to account for different randomization ratios across pts)7; ae, adverse event; ad, atopic dermatitis; bp, parent trial baseline; dlqi, dermatology life quality index; e, number of adverse events; easi, eczema area and severity index; iga, investigator’s global assessment; iqr, interquartile range; itch nrs, peak worst weekly itch nrs; locf, last observation carried forward; mnri, modified non-responder imputation; n, number of patients achieving the indicated metric, or with ≥1 event; ne, number of events; np, number of patients; n, number of patients with recorded observation; nrs, numerical rating scale; pye, patient-years of exposure; pt, parent trial; q2w, every 2 weeks; scorad, scoring atopic dermatitis; sd, standard deviation; tci, or topical calcineurin inhibitor; tcs, topical corticosteroids. limitations • the analysis presented here represents a subgroup of patients who were eligible, chose to enter from two of the pts and were treated for two years in ecztend by the time of data cutoff, and as such, the data may not be generalizable to the full tralokinumab population (see figure 1b). analyses on the full two-year cohort were previously presented4) in ecztend, worst itch nrs was assessed based on recall of the previous week before the visit figure 3. percent response from parent trial baseline in disease severity, itch, and life quality over 3 years figure 1. schematic of (a) ecztend interim analysis of patients previously treated with tralokinumab monotherapy for 52 weeks in ecztra 1 and 2, followed by 104 weeks of treatment in ecztend and (b) patient disposition at parent trial completion, ecztend baseline, and at april 30, 2021 data cutoff https://www.ismpp.org/gpp3 skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 518 brief article adult-onset still's disease with an atypical cutaneous manifestation shae margulies, bs1, nicole nagrani, md2, paul rodriguez-waitkus, md, phd2, lilia correaselm, md2 1 university of florida college of medicine, gainesville, fl 2 university of south florida morsani college of medicine, department of dermatology and cutaneous surgery, tampa, fl adult-onset still’s disease (aosd) is a rare systemic inflammatory disorder that is characterized by daily fevers, arthralgias, and rash without evidence of infection. aosd can present itself in various ways, making the diagnosis a difficult one to make. more recently, there has been an increasing number of cases reported with atypical cutaneous presentations. herein, we describe a case of aosd with an atypical cutaneous presentation in a black female to add to the growing body of literature. a 37-year-old skin type fitzpatrick vi female with past medical history significant for obesity, solitary kidney, and paranoid personality disorder presented to the hospital with complaints of subjective fevers, cough, and lower extremity pain following a motor vehicle accident which occurred 15 days prior abstract adult-onset still’s disease (aosd) is a rare systemic inflammatory disorder, characterized by daily fevers, arthralgias, and rash without evidence of infection. recently there has been a growing number of cases reported with atypical cutaneous manifestations. we present a 37year-old type vi fitzpatrick skin type female who was seen in the hospital for a pruritic rash on her chest, back, and legs. skin examination was significant for hyperpigmented papules coalescing into plaques on the chest, and hyperpigmented linear patches and excoriated plaques on the back and legs. punch biopsy showed acanthosis and numerous apoptotic keratinocytes in the upper layers of the epidermis, which was characteristic of aosd. as of recently, there is a growing body of evidence describing an atypical eruption of persistent, pruritic papules and plaques with typical histologic findings of aosd. further, these atypical features may be associated with more severe symptoms, higher incidence of macrophage activation syndrome, and possible delayed malignancy. due to the scarcity of atypical cutaneous manifestations reported in the literature, these eruptions have not been included in the diagnostic criteria and can therefore be overlooked and misdiagnosed. prompt recognition of these atypical eruptions is imperative to prevent a worsening prognosis and serious adverse effects. introduction case presentation skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 519 to presentation. within a few days of admission, she developed a pruritic rash that involved the face, chest, abdomen, legs, and hands. dermatology was consulted. skin examination was significant for hyperpigmented papules coalescing into plaques on the chest in a v-shaped distribution (figure 1). on the back and legs there were hyperpigmented linear patches intermixed with linear excoriations (figure 2). additional clinical findings included cyclical fevers, diffuse lymphadenopathy, elevated ferritin, pericardial effusion and pulmonary infiltrates. laboratory evaluation revealed an elevated ferritin of 16,580 ng/ml, an elevated erythrocyte sedimentation rate (esr) of >130 mm/h, and an elevated c-reactive protein (crp) of 19.25 mg/l. all infectious etiologies were ruled out. a punch biopsy of the chest showed skin with acanthosis and numerous apoptotic keratinocytes predominantly located in the upper layers of the epidermis. within the dermis, there is a superficial perivascular inflammatory infiltrate composed of lymphocytes, neutrophils and scattered melanophages. no interface changes were identified. figure 1. hyperpigmented papules coalescing into plaques in a v-shaped distribution figure 2. hyperpigmented linear patches and linear excoriations in the setting of fever, polyarthralgia, pericardial effusion, elevated esr, crp, and ferritin, rash, and characteristic biopsy findings, she was diagnosed with aosd. she was treated with a prednisone taper, colchicine 0.6mg twice daily, as well as triamcinolone 0.5% twice daily as needed for her pruritic rash. prednisone taper consisted of 50mg twice daily for 10 days, then 60mg daily decreased by 10mg each week until she reached 20mg, where it was then tapered by 5mg weekly. she showed very mild improvement of the pruritus and rash in the hospital. on outpatient rheumatology follow up, she had no recurrent flares of the rash, and her inflammatory markers were trending down. at this time, her prednisone taper was being decreased by 5mg weekly, and during follow up she was taking 15mg daily with complete resolution of her rash. systemic therapy, such as anakinra, may be needed in skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 520 table 1. yamaguchi criteria for the diagnosis of aosd1 diagnosis is made with  5 criteria present,  2 being major criteria with no exclusion criteria present major criteria fever 39 for  1 week arthralgia or arthritis  2 weeks typical nonpruritic salmon-colored rash leukocytosis  10,000/mm3 minor criteria pharyngitis lymphadenopathy hepatomegaly and/or splenomegaly liver dysfunction negative rheumatoid factor and antinuclear antibody exclusion criteria infection, malignancy, or other rheumatic diseases skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 521 the future if she is unable to taper off the steroids. aosd is a rare, multisystem inflammatory condition with an unknown etiology. due to its uncommon occurrence and variable presentation, diagnosis of aosd may be delayed. there is a broad differential diagnosis for patients with overlapping features of aosd, including infection, autoimmune disease, autoinflammatory disease, and malignancy. the proposed yamaguchi major criteria for aosd, summarized in table 1, consists of fever, arthralgias, typical rash, and leukocytosis, while the minor criteria include pharyngitis, lymphadenopathy and/or splenomegaly, liver dysfunction, and the absence of rheumatoid factor and antinuclear antibody.1 the typical rash of aosd is characterized by nonpruritic, salmon-pink macules, papules, and plaques that coincide with fever spikes. as of recently, more cases of aosd have been reported in the literature with atypical cutaneous presentations. there is a growing body of evidence describing the atypical eruption of persistent, pruritic papules and plaques in patients with aosd.2-8 these persistent lesions have characteristic findings on histology, including dyskeratotic cells in the upper epidermis and a lymphocytic infiltrate in the papillary dermis.2 in patients who develop linear lesions with the appearance of excoriations, as seen in our patient, histology remains consistent, and this therefore represents koebner’s phenomenon.9 skin findings differ from the typical rash in both morphology and time course, leading to further difficulty making the diagnosis of aosd. moreover, these atypical features may be associated with more severe symptoms and are theorized to be a negative prognostic factor for disease.10-12 a cohort study including 150 patients with aosd found that those with atypical persistent pruritic eruptions had higher levels of lactate dehydrogenase and ferritin and a higher rate of macrophage activation syndrome than patients with the typical evanescent rash.10 dyskeratotic cells on histology in persistent pruritic eruptions have been linked to an increase in il-18 and subsequently a worse prognosis.11 further, aosd has been increasingly associated with delayed malignancies, commonly breast cancer and lymphoma.13 in a review of 19 patients with atypical presentations of aosd, diagnostic workup for malignancy showed hepatosplenomegaly in 26%, lymphadenopathy in 11%, and pleural and pericardial effusion in 5%.13 early recognition of aosd is important as to not delay treatment in patients with diffuse systemic disease. due to the scarcity of atypical cutaneous manifestations reported in the literature, these eruptions have not been included in the diagnostic criteria and can therefore be overlooked and misdiagnosed. prompt recognition of these atypical eruptions is imperative to prevent a worsening prognosis and serious adverse effects such as macrophage activation syndrome or delayed recognition of malignancy. conflict of interest disclosures: dr. correa is a consultant for accutec blades and a consultant and a researcher for novartis pharmaceutical. funding: none corresponding author: lilia correa-selm, md discussion conclusion skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 522 department of dermatology and cutaneous surgery university of south florida college of medicine 13220 usf laurel drive, 5th floor tampa, fl 33612 phone: (813) 974-4270 email: lcorrea1@usf.edu references: 1. yamaguchi, m., ohta, a., tsunematsu, t., et al. (1992). preliminary criteria for classification of adult still’s disease. the journal of rheumatology, 19(3), 424–430. 2. fernández camporro, á., rodríguez diaz, e., betetagorriti, v., gonzalvo rodríguez, p., & álvarez cuesta, c. (n.d.). still’s disease with persistent atypical dermatomyositis-like skin eruption: two cases associated with macrophage activation syndrome. clinical and experimental dermatology, n/a(n/a). https://doi.org/10.1111/ced.15294 3. kam, s., ishii, l., zwerner, j. p., & dewan, a. k. (2022). fever and flagellate dermatosis in an otherwise healthy woman. clinical and experimental dermatology, 47(1), 220–222. https://doi.org/10.1111/ced.14907 4. patidar, a., parikh, p. m., balai, m., & mittal, a. (2020). flagellate rash in adult-onset still’s disease. indian dermatology online journal, 12(1), 159–161. https://doi.org/10.4103/idoj.idoj_178_20 5. patra, s., bhari, n., mohta, p., singh, s., ramam, m., & agarwal, s. (2019). adult-onset still’s disease presenting as blotchy and flagellate pigmentation. indian journal of dermatology, venereology and leprology, 85(6), 626– 628.https://doi.org/10.4103/ijdvl.ijdvl_513_18 6. pawar, m., zawar, v., &kumavat, s. (2020). persistent pruritic papules and plaques and flagellate erythema as presenting manifestations of an adult onset still's disease.. actas dermo-sifiliograficas, 111(9), 794–796. https://doi.org/10.1016/j.ad.2019.01.031 7. kikuchi, n., satoh, m., ohtsuka, m., & yamamoto, t. (2014). persistent pruritic papules and plaques associated with adult-onset still’s disease: report of six cases. the journal of dermatology, 41(5), 407–410. https://doi.org/10.1111/1346-8138.12426 8. suzuki, k., kimura, y., aoki, m., et al. (2001). persistent plaques and linear pigmentation in adult-onset still’s disease. dermatology, 202(4), 333–335. https://doi.org/10.1159/000051669 9. lee, j. y.-y., yang, c.-c., & hsu, m. m.-l. (2005). histopathology of persistent papules and plaques in adult-onset still’s disease. journal of the american academy of dermatology, 52(6), 1003–1008. https://doi.org/10.1016/j.jaad.2005.02.032 10. ding, y., tang, s., li, s., et al. (2021). risk of macrophage activation syndrome in patients with adult-onset still’s disease with skin involvement: a retrospective cohort study. journal of the american academy of dermatology, 85(6), 1503– 1509. https://doi.org/10.1016/j.jaad.2021.02.005 11. maeda-aoyama, n., hamada-ode, k., taniguchi, y., et al. (2020). dyskeratotic cells in persistent pruritic skin lesions as a prognostic factor in adult-onset still disease. medicine, 99(6), e19051. https://doi.org/10.1097/md.0000000000019051 12. zuelgaray, e., battistella, m., sallé de chou, c., et al. (2018). increased severity and epidermal alterations in persistent versus evanescent skin lesions in adult-onset still disease. journal of the american academy of dermatology, 79(5), 969– 971. https://doi.org/10.1016/j.jaad.2018.05.020 13. sun, n. z., brezinski, e. a., berliner, j., et al. (2015). updates in adult-onset still disease: atypical cutaneous manifestations and associations with delayed malignancy. journal of the american academy of dermatology, 73(2), 294–303. https://doi.org/10.1016/j.jaad.2015.04.063 https://doi.org/10.1097/md.0000000000019051 https://doi.org/10.1016/j.jaad.2018.05.020 skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 657 original research socioeconomic factors in the diagnosis and treatment of malignant melanoma in hispanic vs. non-hispanic patients: a national cancer database (ncdb) study julia griffin, bs1, sarah j. aurit, ms2, timothy malouff, md3, peter silberstein, md1 1 creighton university school of medicine, omaha, ne 2 university of nebraska at lincoln, lincoln, ne 3 university of oklahoma health sciences center, oklahoma city, ok skin cancers are the most common cancers in the united states and worldwide, with an estimated annual cost of treating skin cancers about $8.1 billion.1 while basal cell carcinoma (bcc) and squamous cell carcinoma (scc) are the most common, the incidence of melanoma, the most lethal form of skin cancer, diagnosed annually increased by 27% over the past decade (2003-2023). in 2023, it is estimated that 186,680 cases of melanoma will be diagnosed, of which 97,610 cases will be invasive.1 localized melanoma has an excellent prognosis, with five-year abstract background: the incidence of melanoma is rapidly increasing in the united states. there is a paucity of research of how melanoma affects the hispanic population, the quickest growing population. objective: to identify and understand how socioeconomic factors affect a hispanic patients health outcome and treatment of malignant melanoma with comparisons to white, nonhispanic (wnh) patients. methods: a retrospective study utilizing the national cancer database (ncdb) was completed investigating hispanic patients (n=2282) and wnh patients (n=190,469) with stage i-iv malignant melanoma. outcome and socioeconomic variables were identified and compared across groups. data was analyzed with spss and sas statistical software; kaplan-meier survival curves and cox proportional hazard regression models were computed. results: hispanic patients have 2.50 higher odds of being diagnosed with stage iv vs. stage i melanoma when compared to wnh patients (95% ci 2.20-2.86, p<0.001). differences in insurance status, income, education, facility type, facility location, urban/rural, charlson-deyo score, and stage are all statistically significant for wnh compared to hispanic patients (p<0.05). conclusion: in addition to various socioeconomic disparities, hispanic patients are more likely than wnh patients to have melanoma diagnosed at higher stages and subtypes with worse prognosis. clinicians need to provide skin cancer education and prevention and mobilize resources to serve this diverse population. introduction skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 658 overall survival (os) rates of 99% for local disease. this decreases with advanced stage, with a 5-year os of 66% if spread to regional lymph nodes and 27% if metastatic.2 melanoma disproportionately affects men more than women; it is predicted that in 2021 62,260 men and 43,850 women were affected with invasive melanoma.1,3 in addition to gender, melanoma more commonly affects caucasians, with the lifetime risk of melanoma of about 1 in 38 for caucasians, 1 in 167 for hispanics, and 1 in 1,000 for african americans.4 melanoma affects people of color differently as it is often diagnosed in atypical locations as thicker, more advanced melanomas with more regional involvement which leads to worse prognoses.5-9 as patients of hispanic ethnicity are among the fastest growing population in the united states, and there is a paucity of data about disease specific factors in this ethnic group, it is vital to identify the incidence and disparities regarding the diagnosis and treatment in this population.10 as with other underserved ethnic groups, hispanic patients tend to present with later stage disease and a higher risk for regional involvement compared to caucasian patients.5-9 in fair-skinned hispanics, melanomas may be more likely to be found on the trunk and legs; in dark-skinned hispanics melanomas are more likely to be found on the feet.8 females tend to present with melanoma on the lower limb and hip while males tend to present with melanoma on the trunk.9 additionally, the most common forms of melanoma in hispanic patients include superficial spreading melanoma, acral lentiginous melanoma, and nodular melanoma, which have poorer outcomes.9 although there are data using the national cancer database (ncdb) informing the socioeconomic factors and disparities, to our knowledge, this is the first study to address melanoma specifically in the hispanic population. in this study, we aim to identify socioeconomic factors that affect a hispanic patient's health outcomes and treatment of malignant melanoma with comparisons to white, non-hispanic (wnh) patients. utilizing the ncdb, a nationwide clinical oncology outcomes database, we retrospectively analyzed the data to determine the socioeconomic factors associated with diagnosis and treatment of invasive melanoma in hispanic patients (n=2282) versus wnh patients (n=190,469). our definition of hispanic includes people of latino and spanish origin. patients with confirmed malignant melanoma were identified by icd-0-3 histology. outcome and socioeconomic variables were analyzed, including age, american joint committee on cancer (ajcc) stage groups i-iv, spanish hispanic origin, and race, primary payor at diagnosis, charlson-deyo score, zip code level median household income, zip code level education, facility type, urban/rural, and facility location. patients were excluded for missing or incomplete data with certain variables as shown in figure 1. if the data was coded as blank/not available, the cases are labeled “variable value missing.” if the data was coded as unknown then the cases are labeled “variable value unknown.” ajcc clinical stage group only included stage i-iv because this analysis investigated invasive or malignant melanoma; not melanoma in situ/stage 0. the data was analyzed using spss and sas statistical software. analysis was completed methods skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 659 figure 1. description of included and excluded variables. skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 660 of demographic and socioeconomic variables assessing percentages and p-values. kaplan-meier survival curves were plotted to estimate overall survival. multivariable analyses was performed with cox proportional hazard regression models to estimate the independent effect of patient characteristics after controlling for other covariates. the variables included were chosen to evaluate how socioeconomic factors and treatment options influence health outcomes. the proportionality of hazards assumption was examined with log-negative-log survival plots and time-dependent coefficients were used to determine if there was an interaction between time and each variable of interest. the functional form of age was investigated with plots of martingale residuals, and we accommodated for the clustering of patients within a facility with a robust sandwich covariance estimator. a total of 192,751 documented cases of melanoma between 2004-2017 are included. of these patients, there are 2,282 hispanic patients and 190,469 wnh patients. table 1 summarizes the baseline patient characteristics. about 9.3% of hispanic patients were uninsured and 10.9% were on medicaid, compared to 1.9% and 2.3% of wnh patients, respectively. hispanic patients were more likely than wnh patients to live in zipcodes with lower annual income and lower rates of high school graduates. higher stages (stage iii and iv) were more common in wnh patients than hispanic patients. hispanic patients have some 2.50 higher odds being diagnosed with stage 4 vs. stage 1 when compared to wnh patients (95% ci 2.20-2.86, p<0.001). differences in insurance status, income, education, facility type, facility location, urban/rural, charlson-deyo score, and stage are all statistically significant for wnh compared to hispanic patients (p<0.05). both hispanic and wnh patients were primarily male with an average age of 61 and 64 years, respectively. approximately 16% of wnh and 19% of hispanic patients had a charlson deyo comorbidity score of 1 or above, and most received treatment at an academic/research program in a metro area. hispanics were more likely to receive treatment in the pacific and south atlantic while wnh patients were more likely to receive care in the south atlantic and middle atlantic. wnh patients were more likely to be diagnosed with stage i disease compared to hispanic patients (68% vs 53%), while hispanic patients were more likely to be diagnosed with metastatic disease (12% vs 6%) as shown in table 1. wnh patients had higher incidences of lentigo maligna melanoma (6.1% vs. 2.7%) and superficial spreading melanoma (32.1% vs. 21.3%) compared to hispanics. also, hispanics had a higher percentage of acral lentiginous melanoma compared to wnh individuals (8.5% vs. 1.1%). the most common primary sites (anatomic site of origin for the cancer) for diagnosis of melanoma had different prevalence for the wnh and hispanic groups. wnh patients more commonly had melanoma diagnosed on skin of trunk (30.6%), skin of upper limb and shoulder (25.3%), and skin of lower limb and hip (16.8%). meanwhile, hispanics more commonly found melanoma on the skin of lower limb and hip (31.6%), skin of trunk (22.4%), and skin of upper limb and shoulder (17.7%). results skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 661 table 1. demographic and clinical characteristics stratified by ethnicity. wnh hispanic p patients 190,469 2,282 age 64 [54-74] 61 [5172] <.001 biological sex <.001 female 39.2 45.3 male 60.8 54.7 insurance status <.001 uninsured 1.9 9.3 private 50.4 45.1 medicaid 2.3 10.9 medicare 44.4 34.4 other government 1.1 0.4 zip code-level income quartile <.001 <$38,000 10.0 16.8 $38,000-$47,999 20.3 22.4 $48,000-$62,999 27.3 28.9 ≥$63,000 42.4 31.9 zip code-level education (no high school diploma) <.001 ≥21.0% 9.0 35.6 13.0%-20.9% 21.1 22.9 7.0%-12.9% 35.6 22.6 <7.0% 34.3 19.0 stage <.001 1 68.3 53.0 2 20.6 24.7 3 4.7 10.0 4 6.3 12.2 charlson-deyo score <.001 0 84.1 9.1 1 12.3 6.5 2 2.5 9.6 3 1.0 0.8 facility type <.001 community cancer program 5.8 4.3 comprehensive community cancer program 34.1 27.3 academic/research program 49.9 59.2 skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 662 integrated network cancer program 10.2 9.3 urban/rural <.001 metro 85.1 95.5 urban 13.3 4.1 rural 1.6 0.5 facility location <.001 new england 6.7 3.1 middle atlantic 16.8 14.0 south atlantic 23.0 24.7 east north central 16.6 9.2 east south central 6.2 1.7 west north central 8.8 2.2 west south central 4.3 11.4 mountain 4.5 6.6 pacific 13.1 27.0 figure 2. kaplan meier curve for wnh vs. hispanic patients with melanoma. skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 663 in addition, kaplan meier curves were created to analyze the survival outcomes of wnh and hispanics seen in figure 2. unadjusted survival was initially seen via the log-rank test (p < .001). as shown in table 2, wnh have higher survival rates at 3, 5, and 10 years compared to hispanics. lastly, a multivariable cox regression model was estimated to assess risk of mortality differences associated with ethnicity. these results are shown in table 3. this statistical analysis demonstrates that there are many significant differences between wnh and hispanic melanoma diagnoses, treatment modalities, socioeconomic factors, and survival outcomes. to date, our study is the first using the ncdb to determine health disparities in the rapidly growing hispanic ethnic group. our data suggest that, on average, hispanic patients are diagnosed with higher stages of melanoma than wnh patients. specifically, hispanic patients have 2.50 higher odds of being diagnosed with stage iv vs. stage i when compared to wnh patients (95% ci 2.20-2.86, p<0.001). there are likely multifactorial reasons for this, with factors such as poor language proficiency, low health literacy, diminished trust in the healthcare system, limited accessibility to healthcare resources, and no previous established pcp relationships contributing to later staging of a melanoma diagnosis.6-10 in our analysis, factors such as income, education, and insurance status contributed to more advanced and later diagnosis. this is significant, as higher stage is linked to poorer outcomes and overall survival.6-12 similarly, our data found that more hispanic patients were treated at academic centers compared to wnh patients. the factors for this are likely multifactorial, such as transportation, concentration of cancer treating facilities, or rates of melanoma in certain regions, among other variables.6-12 these results exemplify that strategies may need to be implemented to diagnose melanoma earlier in hispanic patients. our study found that hispanic patients are diagnosed at later stages than wnh patients, with approximately 12.3% of hispanic patients diagnosed at stage iv compared to 6.3% of wnh patients. this translates to a difference in survival, with wnh patients having higher survival rates than hispanics. in table 3 it is interesting to note, although not statistically significant (p=0.358) that the hazard ratio (hr) for hispanic vs. wnh patients indicates that hispanics had a 4% lower risk of death. thus, the hr demonstrates that a greater risk of death is associated with higher stage, greater age, medicaid (vs. private insurance), lower income, and lower education level (p<.001). of note, immune checkpoint inhibitors (antictla4, anti-pd-1, and anti-pd-l1) and targeted therapy (braf and mek inhibitors) have been major advances in the treatment of melanoma in the last ten years. although, the use of immunotherapy in our study was not statistically significant it is estimated that the new drugs were likely not used until 20132016, and our data set analyzed patients from years 2004-2017.13,14 our results are similar to previous studies in that hispanic patients have statistically discussion skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 664 table 2. survival rates between wnh and hispanic patients at 3, 5, and 10 years. survival rates wnh hispanic 3-year 83.2 (83.0-83.4) 76.7 (74.8-78.5) 5-year 75.6 (75.4-75.8) 68.3 (66.0-70.4) 10-year 60.7 (60.3-61.0) 55.7 (52.5-59.1) skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 665 table 3. multivariable cox regression model assessing risk of mortality differences between wnh and hispanic patients. hr lower confidence limit upper confidence limit p ethnicity non-hispanic vs. hispanic 0.96 0.87 1.05 0.358 age (per 10 years) 1.67 1.64 1.70 <.001 ajcc clinical stage stage 2 vs. stage 1 2.38 2.30 2.45 <.001 stage 3 vs. stage 1 3.54 3.38 3.71 <.001 stage 4 vs. stage 1 9.86 9.30 10.45 <.001 payor status none vs. private 1.80 1.66 1.96 <.001 medicaid vs. private 2.19 2.03 2.36 <.001 medicare vs. private 1.19 1.16 1.23 <.001 other government vs. private 1.19 1.05 1.35 0.006 zip code-level median household income 38,000-47,999 vs. < 38,000 0.92 0.88 0.95 <.001 < 48,000-62,999 vs. < 38,000 0.89 0.85 0.93 <.001 ≥ 63,000 vs. < 38,000 0.80 0.75 0.86 <.001 zip code-level education (no high school diploma) ≥ 21 vs. < 7 1.11 1.03 1.19 0.008 13-20.9 vs. < 7 1.10 1.05 1.16 <.001 7-12.9 vs. < 7 1.10 1.06 1.14 <.001 chemotherapy yes vs. no 1.84 1.72 1.97 <.001 radiation yes vs. no 1.85 1.76 1.95 <.001 immunotherapy yes vs. no 1.04 0.99 1.10 0.119 skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 666 similar risk of death with a shorter time-todeath. hispanics have higher prevalence of melanoma diagnoses associated with poorer outcomes (acral lentiginous melanoma) and more advanced disease.6,7,9 the location of discovered cancer varies between wnh and hispanic patients, but both groups show high rates of melanoma being diagnosed on the skin of trunk, skin of upper limb and shoulder, and skin of lower limb and hip which is consistent with the study by erin garnett et al.9 cultural barriers, less frequent dermatology exams, a lack of knowledge of preventative skin cancer measures, or ability to monitor lesions due to difficult locations may lead to worse prognoses and higher stages in hispanic patients.6-12 our study, while the findings are important, has limitations worth discussing. although, the ncdb is recognized as a comprehensive database, it does not include patient data diagnosed at non-commission on cancer (coc)-accredited facilities; it only includes about 70% of cancer patients. thus, it is not known if non-coc patient data is consistent with ncdb coc patient data. another limitation of this study was that there were biases inherent of large database reviews including incorrect coding of data; we excluded 301,147 patients due to missing or unknown data. the retrospective nature of the study limited us to the variables documented by ncdb. lastly, the ncdb does not record cancer-specific survival, so we are unable to differentiate between melanoma-specific mortality and all-cause mortality. despite these limitations, our results are consistent with those found in the published literature which supports our conclusions. our study supports the findings that outcomes for hispanic patients diagnosed with melanoma are inferior to those in wnh populations. as the hispanic population is one of the most rapidly growing groups in the us, it is important to take a multi-factorial and multi-disciplinary approach to address these disparities. first, there is a need for new and critical research to better understand major causes of advanced melanoma among hispanic patients. diverse sample populations are needed to evaluate genetic, socioeconomic, and behavioral risk factors. hispanic patients should also be included on all major trials investigating new treatment options for melanoma. secondly, community efforts are vital to create an increased awareness of skin cancer, decrease incidence, increase diagnosis, and improve outcomes. while ensuring cultural competence and language accessibility, primary care physicians and dermatologists must educate hispanic patients about skin cancer risk factors, how to identify abnormal lesions, and how to conduct self-skin exams.12 melanoma’s incidence is rapidly increasing, just as the hispanic population is the most dramatically growing demographic group in the united states. minimal melanoma research has been conducted among diverse populations. we identified several factors associated with poor health outcomes and a malignant melanoma diagnosis for hispanic patients compared to wnh patients. hispanic patients are more likely than wnh patients to have more advanced disease diagnosed at higher stages and melanoma subtype associated with poorer prognosis. additionally, they are more likely to be uninsured and have lower income and education levels which may contribute to lower 3-, 5-, and 10-year survival rates compared to wnh patients. these conclusions increase our competence of health disparities affecting hispanic patients conclusion skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 667 and exemplify that we must mobilize resources to reach vulnerable populations, complete melanoma research among diverse populations, and educate patients about skin cancer to address this growing public health concern. conflict of interest disclosures: none funding: none corresponding author: julia griffin, bs creighton university school of medicine 7500 mercy rd omaha, ne 68124 email: griffinjulia16@gmail.com references: 1. skin cancer foundation. (2023, january). skin cancer facts and statistics. skin cancer foundation. https://www.skincancer.org/skincancer-information/skin-cancer-facts/ 2. cancer facts and figures. (2021). american cancer society. https://www.cancer.org/content/dam/cancerorg/research/cancer-facts-and-statistics/annualcancer-facts-and-figures/2021/cancer-facts-andfigures-2021.pdf 3. skin cancer foundation. (2021). skin cancer prevention. skin cancer foundation. https://www.skincancer.org/skin-cancerprevention/ 4. american cancer society. (2021). key statistics for melanoma skin cancer. american cancer society. https://www.cancer.org/cancer/melanoma-skincancer/about/key-statistics.html 5. melanoma research foundation. (2020). melanoma education. melanoma research foundation. https://melanoma.org/melanomaeducation/melanoma-awareness/ 6. wich, lindsay g, ma, michelle w, price, leah s, sidash, stanislav, berman, russell s, pavlick, anna c, . . . osman, iman. (2010). impact of socioeconomic status and sociodemographic factors on melanoma presentation among ethnic minorities. journal of community health, 36(3), 461-468. 7. jaimes, natalia, oliveria, susan, & halpern, allan. (2013). a cautionary note on melanoma screening in the hispanic/latino population. jama dermatology (chicago, ill.), 149(4), 396397. 8. baum, bertha, & duarte, ana margarita. (2015). skin cancer epidemic in american hispanic and latino patients. in pediatric skin of color (pp. 453-460). new york, ny: springer new york. 9. garnett, erin, townsend, julie, steele, brooke, & watson, meg. (2016). characteristics, rates and trends of melanoma incidence among hispanics in the united states. cancer causes & control, 27(5), 647-659. 10. grace y. chung, gina brown, & desmond gibson. (2015). increasing melanoma screening among hispanic/latino americans: a community-based educational intervention. health education & behavior, 42(5), 627-632. 11. harvey, valerie. (2018). melanoma in us hispanics: recommended strategies to reduce disparities in outcomes. skin of color, 101(4), 243-246. 12. perez, maritza. (2019). skin cancer in hispanics in the united states. j drugs dermatol., 18(3), 117-120. 13. nci staff. (2021). immunothearpy combination most effective as initial treatment for braf+ melanoma. nih national cancer institute. https://www.cancer.gov/news-events/cancercurrents-blog/2021/advanced-melanoma-brafimmunotherapyfirst#:~:text=both%20ipilimumab%20and%20nivo lumab%20were,their%20tumors%20had%20bra f%20mutations. 14. kim t, amaria r, spencer c, reuben a, cooper z, & wargo ja. (2014). combining targeted therapy and immune checkpoint inhibitors in the treatment of metastatic melanoma. cancer biol med, 11(4):237-46. doi: 10.7497/j.issn.20953941.2014.04.002. https://www.skincancer.org/skin-cancer-information/skin-cancer-facts/ https://www.skincancer.org/skin-cancer-information/skin-cancer-facts/ https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2021/cancer-facts-and-figures-2021.pdf https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2021/cancer-facts-and-figures-2021.pdf https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2021/cancer-facts-and-figures-2021.pdf https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2021/cancer-facts-and-figures-2021.pdf https://www.skincancer.org/skin-cancer-prevention/ https://www.skincancer.org/skin-cancer-prevention/ https://www.cancer.org/cancer/melanoma-skin-cancer/about/key-statistics.html https://www.cancer.org/cancer/melanoma-skin-cancer/about/key-statistics.html https://melanoma.org/melanoma-education/melanoma-awareness/ https://melanoma.org/melanoma-education/melanoma-awareness/ https://www.cancer.gov/news-events/cancer-currents-blog/2021/advanced-melanoma-braf-immunotherapy-first#:~:text=both%20ipilimumab%20and%20nivolumab%20were,their%20tumors%20had%20braf%20mutations https://www.cancer.gov/news-events/cancer-currents-blog/2021/advanced-melanoma-braf-immunotherapy-first#:~:text=both%20ipilimumab%20and%20nivolumab%20were,their%20tumors%20had%20braf%20mutations https://www.cancer.gov/news-events/cancer-currents-blog/2021/advanced-melanoma-braf-immunotherapy-first#:~:text=both%20ipilimumab%20and%20nivolumab%20were,their%20tumors%20had%20braf%20mutations https://www.cancer.gov/news-events/cancer-currents-blog/2021/advanced-melanoma-braf-immunotherapy-first#:~:text=both%20ipilimumab%20and%20nivolumab%20were,their%20tumors%20had%20braf%20mutations https://www.cancer.gov/news-events/cancer-currents-blog/2021/advanced-melanoma-braf-immunotherapy-first#:~:text=both%20ipilimumab%20and%20nivolumab%20were,their%20tumors%20had%20braf%20mutations https://www.cancer.gov/news-events/cancer-currents-blog/2021/advanced-melanoma-braf-immunotherapy-first#:~:text=both%20ipilimumab%20and%20nivolumab%20were,their%20tumors%20had%20braf%20mutations skin january 2018 volume 2 issue 1 copyright 2018 the national society for cutaneous medicine 49 brief articles mohs micrographic surgery peripheral margin control prior to en bloc tumor resection: a report of three cases daniel bernstein md a , sara giddings a , hooman khorasani md a a department of dermatology, division of dermatologic and cosmetic surgery, mount sinai school of medicine, new york, ny an otherwise healthy, 58-year-old male presented with a long standing morpheaform basal cell carcinoma of the left midface, involving lip, nose and cheek (figure 1). pathology was remarkable for a deeply infiltrating tumor including perineural and maxillary bone invasion. multidisciplinary care was coordinated with facial plastic surgery. two stages of mohs micrographic surgery (mms) were needed abstract background. mohs micrographic surgery (mms) is an important part of non-melanoma skin cancer (nmsc) management but may even be useful for tumors that cannot be cleared in an office setting. there are sparse reports of mms for peripheral margin control in the dermatology literature but various techniques have been reported. case 1. 58-year-old male with morpheaform basal cell carcinoma of the left midface treated with mms peripheral margin control followed by facial plastic surgery central tumor extirpation and defect repair. case 2. 56-year-old female with recurrent morpheaform bcc of the scalp treated with mms peripheral margin control followed by facial plastic surgery central tumor extirpation and defect repair. case 3: 73-year-old male with multiply recurrent scc of the right lower extremity treated with mms peripheral margin control followed by central tumor extirpation and reconstruction. conclusions: mms peripheral margin control followed by central tumor extirpation and defect reconstruction at a later date in the operating room is an option for deeply invasive, large and aggressive nmsc. benefits include decreased time under general anesthesia and superior rates of tumor clearance. in the interim, the peripheral defect between the central tumor and healthy outer tissue can be sutured closed to decrease patient morbidity. case #1 skin january 2018 volume 2 issue 1 copyright 2018 the national society for cutaneous medicine 50 for peripheral margin control, followed by central tumor extirpation and defect reconstruction in the operating room by facial plastic surgery. figure 1. morpheaform bcc of left midface, preoperative (a) and post-mms peripheral margin control (b). a 56-year-old female with multiple comorbidities including ulcerative colitis, myotonic dystrophy and hypothyroidism presented with a recurrent morpheaform bcc of the scalp. the site had been previously repaired with a skin graft, resulting in an area of focal alopecia (figure 2). pathology was notable for a deeply infiltrating tumor including perineural and deep fascial invasion. multidisciplinary care was coordinated with facial plastic surgery. three stages of mms were needed for peripheral margin control, followed by central tumor extirpation and defect reconstruction in the operating room by facial plastic surgery. figure 2. recurrent morpheaform bcc of the scalp, preoperative (a) and post-mms peripheral margin control (b). a 73-year-old male with a history of severe psoriasis and numerous cutaneous scc’s presented with a very large, ulcerated, multiply recurrent scc of the right lower extremity (figure 3). pathology was notable for a deeply infiltrating tumor with perineural and deep fascial invasion. multidisciplinary case #2 case #3 a b a b skin january 2018 volume 2 issue 1 copyright 2018 the national society for cutaneous medicine 51 care was coordinated with plastic surgery and surgical oncology. two stages of mms were needed for peripheral margin control. the patient was then sent for definitive central tumor extirpation and leg reconstruction. figure 3. recurrent aggressive scc of the right lower extremity, preoperative tumor (a) and post-mms peripheral margin control (b). mms has an established reputation as the treatment of choice for high-risk non-melanoma skin cancers (nmsc). the goal is usually to clear the patient completely with mms and patients that cannot reasonably be cleared in the office are unlikely to be scheduled for mms. however, there are techniques that have emerged for dealing with tumors that are presumably too complicated to clear in the office under local anesthesia alone. staged excisions in the office do not benefit from complete margin control and often leave patients with open wounds for prolonged periods of time when performed in the office. if performed in the operating room, intraoperative frozen sections tend to be even less accurate than standard permanent sections. 1 the “perimeter technique” and the “square technique” (modified staged excisions employed for lentigo maligna) involve removing the perimeter around a tumor in a geometric configuration that is then processed as vertical permanent sections. 2,3 the perimeter gap can then be sutured between stages for less patient a b discussion skin january 2018 volume 2 issue 1 copyright 2018 the national society for cutaneous medicine 52 morbidity. the “spaghetti technique” is very similar to the perimeter technique but the perimeter is determined clinically and the tissue is processed as comprehensive, longitudinal en face permanent sections. 4 these techniques all involve permanent sections, which can avoid melanocyte distortion often seen with frozen sections and may inhibit mms (although, special immunohistochemical stains can be used to identify melanocytes on frozen sections, reenabling melanocyte identification). for complicated nmsc, the two issues of peripheral margin control and deep margin control remain. both can be addressed with intraoperative complete mms but this requires significant coordination of care and allocation of surgical assets that is unlikely to translate to widespread use. 5 furthermore, intraoperative mms can prolong the time a patient is under anesthesia with the corresponding increased risks of significant morbidity and mortality. alternatively, peripheral margins can be cleared in an office setting using mms via the “mohs moat technique” or “ring of mohs technique. 6,7 these techniques modify the “spaghetti technique” by using mms to clear the peripheral margin. once clear, the patient can then be sent for central tumor extirpation and defect repair in the operating room . 6,7 this technique has been employed for different types of nmsc but the literature is sparse on using this technique for highrisk squamous cell carcinoma (scc) or morpheaform basal cell carcinoma (bcc), none of which, to our knowledge, have been previously reported in the dermatology literature. 6-8 our three cases of complex nmsc provide further data supporting the use of mms for peripheral margin control even if the patient will require central tumor extirpation and defect reconstruction at a later date in the operating room. peripheral margin control can be achieved in the office under local anesthesia and reduce the time the patient is in the operating room under general anesthesia, in addition to providing superior rates of tumor clearance via comprehensive, longitudinal en face sectioning. in the interim between the two procedures, the peripheral defect between the central tumor and healthy outer tissue can be sutured closed to decrease patient morbidity. conflict of interest disclosures: none. funding: none. corresponding author: daniel bernstein, md 234 e. 85 th street, 5 th floor new york, ny 10028 212-731-3311 (office) 212-731-3395 (fax) bernstd@gmail.com references: 1) manstein me, manstein ch, smith r. how accurate is frozen section for skin cancers? ann plast surg. 2003 jun;50(6):607-9. 2) mahoney mh, joseph m, temple cl. the perimeter technique for lentigo maligna: an alternative to mohs micrographic surgery. j surg oncol. 2005 aug 1;91(2):120-5. conclusion skin january 2018 volume 2 issue 1 copyright 2018 the national society for cutaneous medicine 53 3) patel an, perkins w, leach ih, varma s. johnson square procedure for lentigo maligna and lentigo maligna melanoma. clin exp dermatol. 2014 jul;39(5):5706. 4) gaudy-marqueste c, perchenet as, taséi am, madjlessi n, magalon g, richard ma, grob jj. the "spaghetti technique": an alternative to mohs surgery or staged surgery for problematic lentiginous melanoma (lentigo maligna and acral lentiginous melanoma). j am acad dermatol. 2011 jan;64(1):113-8. 5) seth r, revenaugh pc, vidimos at, scharpf j, somani ak, fritz ma. simultaneous intraoperative mohs clearance and reconstruction for advanced cutaneous malignancies. arch facial plast surg. 2011 novdec;13(6):404-10. 6) vance kk, pytynia kb, antony ak, krunic al. mohs moat: peripheral cutaneous margin clearance in a collaborative approach for aggressive and deeply invasive basal cell carcinoma. australas j dermatol. 2014 aug;55(3):198-200. 7) ducic y, marra de, kennard c. initial mohs surgery followed by planned surgical resection of massive cutaneous carcinomas of the head and neck. laryngoscope. 2009 apr;119(4):774-7. 8) buck dw 2nd1, kim jy, alam m, rawlani v, johnson s, connor cm, dumanian ga, wayne jd. multidisciplinary approach to the management of dermatofibrosarcoma protuberans. j am acad dermatol. 2012 nov;67(5):861-6. microsoft word july 2020 bar 645 proof final.docx skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 349 brief articles successful deoxycholate acid use in a male patient for resistant lower abdominal wall fat brandon mackey, do1, vernon t mackey, do, faocd, faasms1 1advanced desert dermatology, arizona college of osteopathic medicine, midwestern university of health sciences, peoria, az even after significant weight loss and exercise some patients fail to achieve desirable results in reducing subcutaneous fat in certain recalcitrant areas. the lower abdominal wall can be an area with difficult to remove subcutaneous fat. the number of treatment options available for healthcare providers is continuing to increase and strive to fulfill the growing demand and need for these types of procedures.1 in the past the only treatment options for patients included invasive and expensive surgical procedures with serious potential side effects.2 in the more recent history several less invasive treatments have become available but still carry postoperative recovery time and pain. very recently a few minimally invasive options have become available for patients.3 one of the recent minimally invasive techniques is injection of deoxycholate acid for lipolysis of submental subcutaneous fat. while only currently fda approved for submental subcutaneous fat,3,4 it is used frequently for other body areas with difficult to remove excess subcutaneous fat.5,6 having multiple treatment options available helps patients and healthcare providers tailor treatment plans to a patient’s specific needs, financial resources, and tolerance to the procedure.1 deoxycholate acid is an endogenous secondary bile acid produced in the intestines by bacterial action on cholate, which is secreted by the liver.7 endogenously it facilitates the absorption and transport of dietary fats and other hydrophobic nutrients.7 when injected subcutaneously the action of dca is very limited in protein rich tissues but will retain some action in subcutaneous fat deposits introduction in this patient off-label kybella was effective in improving the contour and removing excess lower abdominal fat after two treatments. while off-label use of kybella is commonly used every day by physicians across the united states, it is not well represented in the literature. this case is presented to aid in the discussion of new, safe, noninvasive treatment techniques in which healthcare demand and delivery has outpaced publication and literature support. abstract skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 350 where the protein concentration is comparatively poor.5,8 with functional activity being limited to fatty deposits, it allows selective lipolysis to targeted tissues and provides a favorable safety profile.5,8,9 it is currently available in a synthetically derived formulation by allergan and available in the united states as kybella.4 a healthy and physically fit 60-year-old caucasian male presented for nonsurgical treatment of his lower abdominal fat. patient reported failure to resolve the excess accumulation of fat in the lower abdominal area after multiple years of strict diet control and extensive daily exercise. physical examination showed bmi <25kg/m2, minimal subumbilical abdominal wall protuberance with mild excess fat and mild skin laxity. a complete history and physical exam failed to show any contraindications or reason to exclude treatment. treatment options where discussed in detail including expectations, complications, side effects, and cost. the patient expressed desire to strictly avoid surgical intervention, liposuction techniques, and cryolipolysis and opted for treatment with the off-label use of kybella. a written consent for the off-label procedure and pictures (figure 1) of the treatment area were obtained prior to procedure start. the patient was placed sitting in the semisupine position in the exam chair. ice packs where applied to the area 5 minutes prior to procedure start while injection sites where planned. patient underwent 5 injections into the subcutaneous fat with a 1/2" 30-gauge needle held perpendicularly to the skin. special attention was given to not inject intradermal or into the underlying muscle or fascia. during injection the abdominal skin and subcutaneous fat was pinched and pulled away from the abdominal wall to further prevent injection into deeper tissues. after injection ice packs were reapplied and the patient reported negligible pain and a mild burning sensation. no bleeding or bruising was appreciated and the patient was observed in the office for 1 hour. the patient reported minimal burning sensation and swelling which gradually declined and resolved by 1 week after injection. the patient also reported negligible tenderness to palpation which resolved by day 14 post injection. the patient was again reexamined at 4 weeks post injection. at that time the patient appreciated a modest improvement in the contour of the treatment area. the patient expressed desire for continued treatment and the patient underwent a second treatment 1 week later utilizing the same technique as before. the patient’s experience was similar to the first treatment and he noticed continued improvement of his lower abdominal contour. the patient was reevaluated 4 weeks later with pictures (figure 2) taken and reported being highly satisfied with the outcome of his treatments. figure 1. (a) patient photos prior to treatment initiation case presentation skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 351 figure 1. (b) patient photos prior to treatment initiation figure 2. patient photos 4 weeks after completing the second treatment targeted lipolysis by injection of dca in off label locations is widespread throughout aesthetic healthcare and is widely advertised and even openly discussed in lay beauty publications. while physicians utilizing this treatment may have become common place in the aesthetic market, comparatively little published literature is available. while standardized treatment regimen may not yet exist for off label locations,5,10,11 physicians have and will continue to develop reasonable nonsurgical treatment plans for diet and exercise resistant lower abdominal wall fat.12 minimally invasive treatments available for patients with resistant abdominal wall fat are growing, and give the ability for physicians to tailor treatment options towards a patient’s individual needs, expectations, and resources.1 as the aesthetic medicine continues to grow, patient preference and satisfaction favors minimally invasive techniques,1 which greatly minimize recovery time improving patient privacy. in this patient off-label kybella was effective in improving the contour and removing excess lower abdominal fat after two treatments. while off-label use of kybella is commonly used every day by physicians across the united states,5,11 it is not well represented in the literature.10 this case is presented to aid in the discussion of new, safe, noninvasive treatment techniques in which healthcare demand and delivery has outpaced publication and literature support. discussion conclusion skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 352 conflict of interest disclosures: none funding: none corresponding author: brandon mackey, do email: mackattackreact@yahoo.com references: 1. small r. aesthetic procedures in office practice. am fam physician. 2009;80:1231-1237. 2. neaman kc, armstrong sd, baca me, et al. outcomes of traditional cosmetic abdominoplasty in a community setting: a retrospective analysis of 1008 patients. plast reconstr surg. 2013;131:403e-410e. 3. fda approves treatment for fat below the chin. available at: https://wayback.archiveit.org/7993/20170406032049/https://www.fda.gov /newsevents/newsroom/pressannouncements/u cm444978.htm . accessed february 28, 2019. 4. kybellatm prescribing information. available at: https://www.accessdata.fda.gov/drugsatfda_docs /label/2018/206333s001lbl.pdf . accessed december 15, 2018. 5. jegasothy sm. deoxycholic acid injections for bra-line lipolysis: two case reports. dermatol surg. 2017 (in press). 6. wollina u, goldman a: atx-101 for reduction of submental fat. expert opin pharmacother. 2015 apr;16(5):755-62. doi: 10.1517/14656566.2015.1019465. epub 2015 feb 27. [pubmed:25724831] 7. national center for biotechnology information. pubchem database. deoxycholic acid, cid=222528, https://pubchem.ncbi.nlm.nih.gov/compound/222 528 (accessed on january 14, 2019) 8. thuangtong r, bentow jj, knopp k, mahmood na, et al. tissue-selective effects of injected deoxycholate. dermatol surg 2010;36:899–908. [pubmed] [google scholar] 9. walker p, lee d: a phase 1 pharmacokinetic study of atx-101: serum lipids and adipokines following synthetic deoxycholic acid injections. j cosmet dermatol. 2015 mar;14(1):33-9. doi: 10.1111/jocd.12122. epub 2015 feb 14. [pubmed:25684122] 10. sykes jm, allak a, klink b. future applications of deoxycholic acid in body contouring. j drugs dermatol 2017;16:43–6. [pubmed] [google scholar] 11. turkmani mg. piezogenic pedal papules treated successfully with deoxycholic acid injection. jaad case rep. 2018;4(6):582–583. published 2018 jun 13. doi:10.1016/j.jdcr.2018.03.027 12. chilukuri s, mueller g. “hands-free” noninvasive body contouring devices: review of effectiveness and patient satisfaction. j drugs dermatol. 2016;15:1402-1406. acknowledgements study funded by galderma research & development, snc, and editorial/poster support provided by galderma laboratories, l.p. results • mean percent reduction in inflammatory lesions between baseline and end of treatment was 14% better in “clear” subjects than “almost clear” subjects, with a reduction of 98.5% lesions vs. 84.5% (p < .001; figure 1).1 • between baseline and the end of treatment more “clear” subjects reported “excellent” improvement than “almost clear” subjects (76.8% vs. 41.8%; p < .001; figure 2).1 • better mean improvements were observed for the “clear” subjects in all 6 of the domains of the dlqi (figure 3). • more “clear” subjects than “almost clear” subjects had a final dlqi score of 0-1 (84% vs. 66%; p < .001). • more “clear” subjects than “almost clear” subjects had (minimal clinically important difference) mcid (≥ 4 points change) in dlqi score (59% vs. 44%; p < .001). • median time to relapse was: 85 days (3 months) for “almost clear” subjects more than 252 days (8 months) for “clear” subjects (figure 4) • relapse was delayed by more than 5 months for “clear” subjects compared to “almost clear” subjects (p < .001; figure 5). introduction • rosacea treatment “success” is defined on the investigator global assessment (iga) scale (0 [clear] through 4 [severe]) as 0 or 1 (“clear” or “almost clear”) this definition is used in clinical trials, by regulatory bodies, and by payers and physicians • is it clinically meaningful to be “clear” vs “almost clear”? what impact is there (if any) on the health related quality of life of rosacea patients? what impact is there (if any) on the time to relapse? achieving an endpoint of completely clear of inflammatory lesions and erythema after treatment of rosacea provides multiple positive patient outcomes: a pooled analysis guy webster, md1, martin schaller, md2, jerry tan, md3, mark jackson, md4; nabil kerrouche, msc5; gregor schafer, md8 1thomas jefferson university, philadelphia, pennsylvania; 2tubingen university hospital, tubingen, germany; 3university of western ontario, london, ontario and windsor clinical research inc, windsor, ontario, canada; 4university of louisville, kentucky, usa; 5galderma r&d, sophia antipolis, france; 6galderma international, paris, france soo.p-rd10412-01 summary • these results emphasize that achieving an endpoint of iga 0 (“clear”) in rosacea may provide multiple patient benefits and a significantly prolonged time before relapse • achieving a treatment outcome of “clear” provides better patient appreciation of rosacea improvement · 35% more subjects reported ‘excellent improvement’ better improvement in quality of life, as measured by dlqi a longer time to relapse · ≥ 5 months relapse-free time references 1. webster g, schaller m, tan j, et al. defining treatment success in rosacea as ‘clear’ may provide multiple patient benefits: results of a pooled analysis. j dermatolog treat. 2017;28(5):469-474. methods study design • objectives to evaluate whether, after successful treatment, “clear” subjects had better outcomes than “almost clear” subjects • methods pooled analysis of 1366 rosacea subjects from 4 randomized controlled trials with iga assessments before and after treatment (ivermectin, metronidazole, or vehicle) • assessments dermatology life quality index (dlqi) questionnaire subject assessment of rosacea improvement time to relapse relapse defined as an iga score of 2 (‘mild’) after a successful 16-week treatment period (iga 0/1) 0 2 4 6 8 10 clear (n = 270) almost clear (n = 487) 3 > 8 figure 4. median time to relapse (months) figure 5. median time to relapse (months) m ea n pe rce nt r ed uc tio n in in fla m m at or y l es io n co un t p < .001 iga 0 (n = 341) iga 1 (n = 1025) 98.5 84.5 50 60 70 80 90 10 0 pe rce nt o f s ub je cts 76.8 20.3 2.3 0.7 41.8 44.6 11.8 1.7 0 10 20 30 40 50 60 70 80 90 1: excellent improvement 2: good improvement 3: moderate improvement 4: no improvement iga 0 (n = 306) iga 1 (n = 878) p < .001 figure 1. better improvement of rosacea figure 2. better patient appreciation table 1. data from 4 previous randomized controlled trials were included in this analysis study interventions dlqi subject assessment of rosacea improvement time to relapse spr.40027 dose range study ivm 0.1% qd, 0.3% qd, 1% qd, 1% bid and vehicle 12-week treatment x – – spr.18170 ivm 1% vs. vehicle 12 weeks x x – spr.18171 ivm 1% vs. vehicle 12 weeks x x – spr.40173 ivm 1% vs. metro 0.75% 16 weeks (36-week follow-up) x x x pe rce nt o f s ub je cts iga 0 (n = 341) iga 1 (n =1003) 16.1 84.2 58.7 16.9 66.0 44.3 0 10 20 30 40 50 60 70 80 90 100 dlqi score 0 1 baseline dlqi score 0 1 end of treatment mcid ≥ 4 end of treatm ent p < .001 p < .001 • dlqi scores: 0 1 = no effect at all on the patient’s life 2 5 = a small effect on the patient’s life 6 10 = a moderate effect on the patient’s life 11 20 = a very large effect on the patient’s life 21 30 = an extremely large effect on the patient’s life figure 3. better improvement in qol pe rce nt o f s ub je cts r em ai ni ng w ith ou t r el ap se 0 10 20 23 30 40 50 54 60 70 80 90 100 time in days iga at the end of the treatement period clear almost clear median time to relapse “clear’ subjects: >252 days 0 14 28 42 56 70 84 96 112 126 140 154 168 182 196 210 224 238 252 median time to relapse “almost clear’ subjects: 85 days p < .0001 figure 5. representative photographs (10355-108-028) iga score: 3 2 1 0 fc17postergaldermawebsterachievingcompleteyclearlesions.pdf powerpoint presentation › the 23-gene expression profile (gep) and 35-gep tests are clinically available, objective ancillary diagnostic tools that facilitate diagnosis of melanocytic lesions with ambiguous histopathology. the tests use proprietary algorithms to produce results of: suggestive of benign neoplasm; intermediate (cannot rule out malignancy); or suggestive of malignant neoplasm with high accuracy.1-6 › communication between the diagnosing dermatopathologist/pathologist and the treating clinician is key to establishing appropriate patient management.7,8 there are circumstances when a dermatologist may find additional diagnostic information helpful in determining excision and follow-up actions.9,10 a clinical impact study of dermatologists’ use of the 23or 35-gene expression profile tests to guide surgical excision and enhance management plan confidence background acknowledgments & disclosures references › asf has served as a consultant for castle biosciences, inc. kla, bbr, jjs, bhr, jhr, sjk, and msg are employee shareholders of castle biosciences, inc. the study was supported by castle biosciences, inc. results aaron s farberg, md1, kelli l ahmed, phd2, briana b rackley, phd2, jennifer j siegel, phd2, brooke h russell, phd2, jason h rogers, msc2, sarah j kurley, phd2, and matthew s goldberg, md2,3 1baylor scott & white health system, dallas, tx 2castle biosciences, inc., friendswood, tx 3icahn school of medicine at mount sinai, new york, ny for more information: afarberg@castlebiosciences.com methods › clinicians were invited for study participation based on prior use of diagnostic gep testing (minimum 3 encounters with gep results). 32 board certified dermatologists participated in this institutional review board (irb)-approved study. clinicians were asked 4 questions per scenario: 1) how would you treat the patient? (no further treatment necessary, no further treatment necessary if lesion appears completely excised, excise <5 mm margins (narrow but complete), excise ≥5 mm margins (but <1 cm), wide local excision (excise ≥1 cm); 2) which follow-up schedule would you recommend? (every 12, 6, 3 or every month); 3) how confident are you in this management plan? (1 (not confident), 2 (slightly confident), 3 (somewhat confident), 4 (fairly confident), 5 (completely confident). › clinical and diagnostic information for 6 uncertain patient scenarios was provided to the clinicians (table 1). diagnostic information was taken from real-world pathology reports of melanocytic lesions and displayed in mock form including the diagnosis and microscopic description. clinical information was based on common clinical situations that may alter patient treatment. gep test results were either not provided (baseline), benign, or malignant for each patient scenario. › gep results can aid dermatologists in decision making to achieve appropriate management plans. › management changes, including surgical excisions and follow-up frequency, were aligned with gep results for these uncertain clinical scenarios. › scenario-specific details demonstrate that a personalized approach can be achieved with gep. conclusions table 1. ambiguous lesion scenarios from real-world pathology reports figure 1. overall clinical impact across all ambiguous scenarios presented at the 42nd annual fall clinical dermatology conference, october 20-23, 2022, las vegas, nv (encore presentation in part from asds 2022) scan for more info › clinical impact was assessed by calculating the mean percent of no change, increase in change, or decrease in change relative to no gep results for each scenario and normalized to 100%. figure 2. gep results impact surgical excision planning, including margin decisions here we present dermatologist management plans and confidence utilizing diagnostic gep results in uncertain clinical and diagnostic scenarios. ›. results clinical impression diagnosis included excision recommendation cosmetic site melanocytic neoplasm, atypical melanocytic proliferation no cosmetic site dysplastic nevus with features of regression yes personal history of melanoma melanocytic neoplasm, atypical melanocytic proliferation no personal history of melanoma melanocytic neoplasm, deep penetrating yes comorbidities atypical intraepidermal melanocytic proliferation (aimp) yes high clinical suspicion atypical intraepidermal melanocytic proliferation (aimp) yes clinical impact: the vast majority of excision decisions and follow-up changes were aligned with gep results across the uncertain scenarios. in addition, there was an increase in overall management plan confidence with a gep result. › figure 3. gep results alter follow-up frequency › surgical margins: when a malignant gep result is provided, there was an increase in surgical treatment for most scenarios. when a benign gep result was received, there was a decreased in surgical management in most scenarios. › follow-up frequency: shown here is a representation of how gep results can alter that cadence resulting in a tailored strategy. 1. clarke, l. e. et al. j cutan pathol 2015. 42 (4) 244–252. 2. clarke, l. e. et al. cancer 2017. 123 (4) 617–628. 3. clarke, l. e. et al. personalized medicine 2020. 17 (5) 361–371. 4. estrada, s. et al. skin 2020. 4 (6) 506–522. 5. ko, j. s. et al. cancer epidem biomar prev 2017. 26 (7) 1107–1113. 6. ko, j. s. et al. human pathology 2019. 86 213–221. 7. smith, shane d. b., et. al. jama dermatol. 2021. 157(9):1033-1034. 8. cockerell, c. dermatol surg. 2018. 44(2):175-176. 9. cockerell c, et al. personalized medicine. 2017. 14(2):123-130. 10. farberg, a. et al. skin 2020. 4 (6) 523–533. malignant gep baseline (no gep) benign gep malignant gep baseline (no gep)benign gep excision follow-up confidence gep result a v e ra g e % c h a n g e benign benign malignantmalignant benign malignant -50 50 0 100 d e c re a se in c re a se baseline https://castletestinfo.com/mypath-melanoma-diffdx-melanoma/scientific-references/ https://castletestinfo.com/mypath-melanoma-diffdx-melanoma/scientific-references/ dd_01_035 fcd poster encore derm survey v5 to submit slide 1 fall clinical dermatology conference, las vegas, 20-23 october 2022 brian berman1 and paul tomondy2 1department of dermatology and cutaneous surgery, university of miami miller school of medicine, miami, fl, usa; 2almirall llc, malvern, pa, usa. • cunningham et al1 compared the efficacy and tolerability of 5% 5fluorouracil (fu) cream + 0.005% calcipotriol ointment combination (fu+c) with fu + vaseline combination (fu+v) treatment of actinic keratosis (aks). • the fu+v control resulted in 0% of participants having complete clearance of face aks and an unexpectedly low 4% of participants developing severe erythema, possibly due to vaseline interfering with fu absorption. • mohney et al2 concluded that petrolatum + 5-fu is an inappropriate control and no superiority claims from that study can be made vs topical fu. • we report a 20-fold reduced penetration of fu in the presence of vaseline (fu+v), and a 73% reduction in fu penetration in the presence of calcipotriol ointment (fu+c). • this is a mass balance study comparing marketed 5-fu alone (fu) and 1:1 weight combinations in vaseline (fu+v), 0.005% calcipotriol ointment (fu+c) and vanicream (fu+vanicream). • in vitro percutaneous absorption and penetration through dermatomed human cadaver skin were assessed. after passing initial visual inspection, barrier integrity of the skin tissue was evaluated using transepidermal electrical resistance measurement. skin permeation (5-6 specimens for each test preparation) into receptor medium was studied at a clinically relevant 8 hours. methods • combining 5% 5-fu cream with vaseline interfered with the fu penetration through skin, which was 20-fold lower with fu+v than with fu. • this degree of reduction in penetration is greater than simply explained by the lower final fu concentration in fu+v applied (2.5%). • this markedly reduced penetration of fu in the presence of vaseline (fu+v), taken with the 73% reduction in fu penetration in the presence of calcipotriol ointment (fu+c), further point to the inappropriateness of using a fu+v combination as a control for clinical studies and could lead to erroneous superiority claims. • bb received consulting honoraria from almirall, biofrontera, bms, pfizer, evommune, aiviva, sirnaomics, pulse and mediwound; • pt is an almirall usa employee. conflicts of interest • 1cunningham et al. j clin invest. 2017; 127:106-116. • 2 mohney et al. j drugs dermatol. 2022;21:60-65 references results • at 8 hours, the mean (standard error of the mean) amount of fu penetrating into the receptor medium was 6,440.2 (1,943.2) ng for fu alone, 316.2 (162.1) ng for fu+v, 1,727.7 (603.4) ng for fu+c and 1,734.6 (542.3) ng for fu+vanicream (fig. 1). • the percentage release amount of fu in receptor at 8 hours was 1.1%, 1.7%, 1.3% and 5.0% and the percentage of fu in the total absorbed dose was 10.1%, 9.2%, 7.3% and 18.7%, respectively (fig. 2). • the concentrations of fu in the receptor at 8 hours are shown in fig. 3. figure 3. mean 5-fluorouracil concentration in total absorbed dose at 8h acknowledgements 0.7 399.9 681,0 996.3 316.2 244.3 602.0 1133.6 1727.7 450.3 945.5 1287.8 1734.6 1198.8 3672.6 4936.5 6440.2 0 500 1000 1500 2000 2500 3000 3500 4000 4500 5000 5500 6000 6500 0 1 2 3 4 5 6 7 8 m e a n a p i (n g ) time point (hours) fu+v fu+c fu+vanicream fu figure 1. mean amount of 5-fluorouracil in receptor from 0 to 8h figure 2. percentage release amount of 5-fluorouracil in receptor from 0 to 8h api, active pharmaceutical ingredient; fu, 5% 5-fu cream alone; fu+v, fu+ 1:1 weight combinations in vaseline; fu+c, fu+ 1:1 weight combinations 0.005% calcipotriol ointment; fu-vanicream; fu+ 1:1 weight combinations vanicream 0.3% 0.5% 0.8% 1.1% 0.2% 0.6% 1.1% 1.7% 0.3% 0.7% 1.0% 1.3% 0.9% 2.8% 3.8% 5.0% 0% 1% 2% 3% 4% 5% 0 1 2 3 4 5 6 7 8 % r e le a s e a m o u n t o f a p i time point (hours) fu+v fu+c fu+vanicream fu api, active pharmaceutical ingredient; fu, 5% 5-fu cream alone; fu+v, fu+ 1:1 weight combinations in vaseline; fu+c, fu+ 1:1 weight combinations 0.005% calcipotriol ointment; fu-vanicream; fu+ 1:1 weight combinations vanicream results api, active pharmaceutical ingredient; fu, 5% 5-fu cream alone; fu+v, fu+ 1:1 weight combinations in vaseline; fu+c, fu+ 1:1 weight combinations 0.005% calcipotriol ointment; fu-vanicream; fu+ 1:1 weight combinations vanicream • writing assistance provided by tfs healthscience. • this study was funded by almirall. 105.4 595.9 578.2 2,146.7 0 500 1000 1500 2000 2500 fu+v fu+c fu+vanicream fu m e a n a p i (n g /m l ) • to compare the skin absorption/penetration of 4 different 5% 5-fu formulations, including fu+v. synopsis objective conclusions human skin absorption and penetration study of four different topical formulations of 5-fluorouracil slide 1 skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 392 brief article are dermatology electives meeting the learning objectives of rotators? deep patel1, md; isha joshi1, mba; alexandra flamm1, md 1 department of dermatology, penn state college of medicine, hershey, pa patients with dermatological conditions are commonly seen in the hospital wards and outpatient clinics in different medical departments. however, studies show that non-dermatological residents and medical students have a discomfort in managing dermatological issues.1,2,3due to limited preclinical dermatology exposure, many students rely on a rotation to supplement their education.4 learners are entering dermatology electives with specific learning objectives in mind and, to our knowledge, there is no literature addressing if those learning objectives are being met by dermatology clinical rotations. our goal is to understand objectives that learners have to allow course directors to tailor electives to specific goals rather than implementing a ‘one size fits all’ elective. a survey was distributed to students and residents who rotated on the general outpatient dermatology clinic at a single academic medical center over the past three years for whom contact information was available. the survey was administered over abstract introduction: learners rely on dermatology electives to supplement their education. our goal is to determine whether electives adequately address the rotators’ learning objectives. methods: a survey was distributed to medical students and residents on a dermatology elective to assess their specific learning objectives and rotation satisfaction. results: the survey had a 50% response rate (n=36). 74.2% of survey respondents were medical students (n=23) and 25.8% were residents (n=8). 57.1% of all rotators were interested improving their morphology/description of skin lesions (n=20). residents were most interested in exposure to basic dermatological procedures (50%, n=4) whereas medical students were most interested in morphology/ descriptions of skin lesions (81.8%, n=18). medical students with an interest in dermatology expressed a greater interest in career exploration (n=8) compared to medical student not interested in dermatology (n=4). discussion: most rotators wanted to gain basic exposure to dermatology, however training level and interest played a role in determining the most important learning objective. residents displayed a greater interested in procedural training while medical students wanted to gain more exposure to basic dermatology skills. conclusion: customizing the dermatology elective to the trainee will allow the greater engagement during the rotation rather than a ‘one size fits all’ elective. introduction methods skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 393 the course of 1 month in the summer of 2020. the survey consisted of three sections: baseline characteristics, rotators’ learning objectives, and whether learning objectives were met. baseline characteristics included training level and medical specialty. to determine learning objectives, participants were asked to provide short answer descriptions of objectives and then asked to select categories their objectives fall into. the categories are listed in table 1. finally, rotators were asked how well the elective fulfilled their objectives. descriptive statistics obtained by frequency analysis were presented for participant characteristics and survey items. the study was approved by the institutional review board at penn state hershey medical center. sas 9.4 statistical software was used for data analysis.5 the survey was sent to 72 rotators and 36 (50.0%) completed the survey (table 1). there were 23 (74.2%) medical students, eight (25.8%) residents, and five who did not specify. of the medical students, seven (31.8%) were third year students, 15 (68.2%) were fourth year students, and one did not specify. common specialties medical students were interested in at the start of their rotation were dermatology (54.6%), family medicine (13.6%), undecided (13.7%), and internal medicine (9.1%). of the residents, five (62.5%) were pgy2 and three (37.5%) were pgy3. all residents were family medicine (62.5%) or internal medicine (37.5%) residents. when responders were asked to select a category for their learning objectives, 57.1% (n=20) of respondents wanted to improve on their morphology/description of skin lesions, 50.0% (n=18) wanted to learn to better manage common dermatological conditions, and 51.4% (n=18) wanted to better identify/diagnose common dermatological conditions. (table 2) residents specifically were interested in the management of common dermatological conditions (n=4, 50.0%) and exposure to basic dermatological procedures (n=4, 50.0%). medical students both interested and not interested in dermatology had similar learning objectives of learning morphology/description of skin lesions (n=18, 81.8%). those interested in dermatology expressed a greater interest in career exploration (n=8, 66.7%). when asked how well the dermatology elective fulfilled learning objectives, 10 reported very well, six reported moderately well, one reported fairly well, one reported poorly, and one reported very poorly. our study reveals that most rotators enter the dermatology elective with a goal of wanting to improve their morphology/description of skin lesions. results discussion skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 394 table 1. characteristics of survey respondents. *1 medical student, 4 residents skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 395 table 2. learning objectives of rotators during their general dermatology clinical rotation: number and percentage of specific learning objectives that all rotators, residents, medical students interested in applying into dermatology, and medical students not interested in applying into dermatology were interested in at the beginning of their clinical rotation. *answer was left blank by one rotator. skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 396 regarding specific goals of learners, residents expressed a greater interested in procedural dermatology while students were focused on learning the basics of description, diagnosis, and management of common dermatological conditions. unsurprisingly, students interested in pursuing a career in dermatology had a specific objective of career exploration. a majority felt that the dermatology elective fulfilled their learning objectives. our data correlates to studies that report the leading reason trainees choose a particular elective is to improve their medical education4 and that dermatology elective improves knowledge for the medical student and resident.6 there are several ways we propose modifying the dermatology elective to enhance the learning experience of rotators. the american academy of dermatology (aad) provides online modules to supplement rotators knowledge in their elective. the aad basic dermatology curriculum has been a part of the rotation for greater than 5 years. however, it is not required and rather is used as a supplementary learning resource in the course handbook. it is not formally taught by faculty or residents but is offered as a self guided lecture series. therefore, the use of this resource by medical students and residents is unknown. creating strategies to further incorporate the curriculum in clerkships can potentially improve the basic learning objectives that both medical students and residents have suggested above. future studies can also examine the usability and helpfulness of the resource for rotators. other strategies our program has considered is creating a formalized mentorship for medical students interested in dermatology with a faculty member to facilitate networking with the department, residency application guidance, and possible research projects that would help with the career exploration learning objective that those students had. finally, because fewer learners, especially from certain groups, had an interest in some subspecialty dermatology exposure, we could consider modifying some of our schedules to allow for more general dermatology exposure. study limitations included distributing surveys in only one academic institution, which may limit generalizability to other institutions with different training. this study may be prone to selection bias, as those having positive experiences with their rotation may feel more inclined to participate in the survey. in addition, the surveys were distributed well after the completion of the rotation for some learners, which may lead to recall bias and explain the low response rate. moreover, not all of our questions were required which contributes to a lower response rate in some questions. this study shows that training level and interest plays a role in learning objectives of students in their dermatology clinical elective. however, there may be gaps in the rotation offered by many programs that have a ‘one size fits all’ dermatology elective for all their rotators. developing an elective targeting a rotator’s specific learning objectives will allow for more engaged learners and will optimize success of clinical rotations. acknowledgement: the authors would like to thank ankita sinharoy for her assistance with the survey administration for this study. conclusion skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 397 conflict of interest disclosures: none funding: none corresponding author: alexandra flamm, md 200 campus drive hershey, pa, 17033, usa email: aflamm@pennstatehealth.psu.edu references: 1. drucker am, cavalcanti rb, wong bm, walsh sr. teaching dermatology to internal medicine residents: needs assessment survey and possible directions. j cutan med surg. 2013;17(1):39–45. 2. khorsand k, brandling-bennett ha. deficiencies in dermatologic training in pediatric residency: perspective of pediatric residency program directors. pediatr dermatol. 2015;32(6):819–824. 3. ulman ca, binder sb, borges nj. assessment of medical students' proficiency in dermatology: are medical students adequately prepared to diagnose and treat common dermatologic conditions in the united states?. j educ eval health prof. 2015;12:18. published 2015 may 17. 4. al-sultan, a. i., parashar, s. k., & al-ghamdi, a. a. electives during medical internship. saudi medical journal. 2003; 24(9): 1006–1009. 5. institute s. base sas 9.4 procedures guide. sas institute; 2015 6. sherertz ef. learning dermatology on a dermatology elective. int j dermatol. 1990;29(5):345–348. skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 332 brief article recognizing multiple diagnoses: von zumbusch generalized pustular psoriasis flare and adverse drug effect jennifer e. yeh, md, phd1,2, ashley ward, md3, and rachel v. reynolds, md4 1 harvard combined dermatology residency program, boston, ma. 2 department of dermatology, stanford university school of medicine, redwood city, ca. 3 department of pathology, beth israel deaconess medical center, boston, ma. 4 department of dermatology, beth israel deaconess medical center, harvard medical school, boston, ma. von zumbusch generalized pustular psoriasis (gpp), also known as acute generalized pustular psoriasis, is a rare and severe type of pustular psoriasis characterized by superficial pustules on the trunk and extremities which coalesce into lakes of pus with erythema and scaling. gpp presents with fever and leukocytosis, and can be associated with life-threatening complications including sepsis. triggers include infection, medications, operations, and hypocalcemia.1, 2 we present a patient with von zumbusch gpp who flared in the setting of a gap in etanercept dosing and hospitalization for hip fracture. we discuss the importance of considering additional diagnoses in patients with this condition who present with laboratory abnormalities that fail to improve with treatment of their gpp. a 74-year-old woman with von zumbusch gpp was transferred from an outside hospital for a diffuse desquamating rash. she had been managed with etanercept 50 mg twice weekly for 10 years with good response, but unfortunately had a lapse in etanercept two months prior to admission due to insurance issues. during outside hospital admission for hip fracture, she developed a psoriasis flare. post-operatively, she developed progressive leukocytosis (wbc increased from 13.7k/ul on admission to 37.7k/ul prior to transfer), conjugated hyperbilirubinemia and mild transaminitis (tbili 0.8 mg/dl, alt 11 iu/l, ast 18 iu/l on admission increased to tbili 4.4 mg/dl, alt 49 iu/l, ast 38 iu/l prior to transfer), low-grade fever, and urinary tract infection (uti) treated with cefazolin, abstract von zumbusch generalized pustular psoriasis (gpp) is a rare and severe type of psoriasis that presents as superficial pustules which coalesce into lakes of pus with erythema and scaling, with associated fever and life-threatening complications including sepsis. here we describe a patient with a history of von zumbusch gpp who presented with erythroderma, neutrophilic leukocytosis, and hyperbilirubinemia in the setting of missed medication dose and hip surgery. while her laboratory abnormalities were initially attributed to a flare of her underlying skin disease, when treatment of her psoriasis flare failed to correct the laboratory abnormalities, review of her biopsy showed evidence of a concomitant adverse drug effect and the patient ultimately expired due to sepsis. introduction case report skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 333 ceftriaxone, piperacillin-tazobactam, and vancomycin. given these systemic findings as well as a progressive rash, she was transferred to our institution for further management. on arrival, she was afebrile and hemodynamically stable. exam revealed erythroderma with light-yellow, thick scaly plaques on the trunk and extremities with superficial desquamation and superficial pustules coalescing into lakes of pus in the right groin fold (figure 1). oral and ocular mucosa were clear. there were no new medications or dose changes prior to outside hospital admission. figure 1. patient’s initial presentation of erythroderma with thick scaly plaques and superficial desquamation a) with pinpoint pustules coalescing into lakes of pus in the skin folds b) labs showed leukocytosis (42.5k/ul with 93% neutrophils), direct hyperbilirubinemia (tbili 6.6 mg/dl, dbili 5.3 mg/dl), transaminitis (alt 41 iu/l, ast 88 iu/l), and normal calcium (8.9 mg/dl). blood cultures were negative. ct abdomen/pelvis revealed no biliary duct dilation. punch biopsy revealed vacuolar interface change with focal subepidermal split, scattered apoptotic keratinocytes, epidermal dysmaturation, diffuse parakeratosis with intracorneal neutrophils, consistent with a drug-related eruption on a background of psoriasis (figure 2). figure 2. punch biopsy showing a) vacuolar interface change, rare apoptotic keratinocytes, epidermal dysmaturation (h&e, original magnification x40), b) rare intermixed eosinophils and neutrophils (h&e, original magnification x100) compatible with a drug reaction, and c) mild epidermal hyperplasia, spongiosis, diffuse parakeratosis, superficial predominantly lymphocytic infiltrate (h&e, original magnification x20), and d) rare intracorneal neutrophils within the parakeratotic scale (h&e, original magnification x40) suggesting a psoriatic diathesis in addition to a drug eruption she was started on cyclosporine 2.5 mg/kg/daily in two divided doses and highpotency topical steroids under occlusion, with plan to transition back to etanercept. within two days of starting cyclosporine, her white blood cell count decreased from 42.5 k/ul to 24.8 k/ul; however subsequently rebounded, peaking at 46 k/ul (figure 3). she was found to have polymicrobial bacteremia and a uti. additionally, liver function tests continued to rise (tbili peaked at 10.9 mg/dl), prompting further skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 334 figure 3. patient’s laboratory value trends for white blood cell count (k/ul) during her hospital admission, paired with recently administered medications. investigation. mrcp was unremarkable, so she underwent a ct-guided liver biopsy. post-procedurally, she became hypotensive with an acute drop in her hematocrit. chest ct revealed a right-sided hemothorax, attributed to the recent liver biopsy, but no source of active bleeding. she was transferred to the icu, where a chest tube was placed. she became hypotensive and pulseless, and resuscitation attempts were unsuccessful. post-mortem, liver biopsy revealed a biliary pattern of liver injury with neutrophils and patchy lymphocytic cholangitis suggestive of drug effect with superimposed sepsis. neutrophilic leukocytosis and liver abnormalities have been reported in patients with gpp, paralleling the evolution of skin lesions and returning to normal upon remission of pustular psoriasis.2 this patient's significant leukocytosis and direct hyperbilirubinemia were initially attributed to her gpp. review of outside records revealed a steady rise in bilirubin and white blood cell count paralleling the flare of her skin disease (figure 3). given some pathological evidence of drug reaction on skin biopsy coupled with transaminitis, dihs was considered however there was no evidence of eosinophilia or facial edema and transaminitis was relatively mild. after starting cyclosporine, her leukocytosis decreased concordant with improvement in skin lesions. however, her leukocytosis then rebounded to higher than admission levels and her liver function test abnormalities remained elevated despite notable improvement in her skin. these abnormalities were later found to be related to sepsis and drug effect, supporting the confluence of multiple factors (gpp, sepsis, and drug-induced liver injury) in her passing. it was challenging to identify the culprit drug for the cutaneous adverse reaction in this case given the patient was recently exposed to multiple antibiotics for her uti (figure 3). the patient had no other known allergies or prior adverse drug reactions. discussion skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 335 in summary, we describe a patient with a history of von zumbusch pustular psoriasis whose leukocytosis and hyperbilirubinemia failed to resolve despite treatment of her underlying psoriasis, and were ultimately found to be related to a concomitant adverse drug effect as well as sepsis. although significant laboratory abnormalities can be associated with a gpp flare, we suggest that when laboratory abnormalities no longer parallel the skin condition, it is critical to investigate other causes such as infection or adverse drug reaction. moreover, because it can be challenging to differentiate between gpp and other diagnoses based on laboratory findings alone, it is critical to engage early in an interdisciplinary approach for the care of these complex patients. conflict of interest disclosures: none funding: none corresponding author: rachel v. reynolds, md beth israel deaconess medical center department of dermatology 330 brookline avenue, shapiro 2 boston, ma 02215-5400 email: rreynold@bidmc.harvard.edu references: 1. viguier m, allez m, zagdanski am, bertheau p, de kerviler e, rybojad m, morel p, dubertret l, lemann m, bachelez h. high frequency of cholestasis in generalized pustular psoriasis: evidence for neutrophilic involvement of the biliary tract. hepatology. 2004;40(2):452-8. [pmid: 15368450]. 2. guerreiro de moura ca, de assis lh, goes p, rosa f, nunes v, gusmao im, cruz cm. a case of acute generalized pustular psoriasis of von zumbusch triggered by hypocalcemia. case rep dermatol. 2015;7(3):345-51. [pmid: 26955330]. conclusion mailto:rreynold@bidmc.harvard.edu skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 406 brief article digital pigmented squamous cell carcinoma in-situ: a case report jordan e lamb, bs1, colleen j. beatty, md2, nancy house, md2, alaina j james, md, phd3 1 university of pittsburgh school of medicine, pittsburgh, pa 2 university of pittsburgh medical center, department of dermatology, division of dermatopathology, pittsburgh, pa 3 university of pittsburgh medical center, department of dermatology, pittsburgh, pa cutaneous squamous cell carcinoma in-situ (sccis), or bowen’s disease, is a keratinocyte neoplasm limited to the epidermis. the classic description is an erythematous, scaly patch or slightly elevated plaque that arises within sundamaged skin of an elderly individual. pigmented sccis is a rare variant that represents between 1.6% and 5.5% of sccis cases1,2 and presents as hyperpigmented, well-demarcated plaque with a velvety, verrucous surface that can clinically mimic malignant melanoma. although skin cancer is less common in people with brown and black skin, these patients are more likely to have pigmented sccis than those with white skin. in some cases, pigmented sccis is located on nonsun exposed sites, suggesting the role of factors other than ultraviolet (uv) radiation in the pathogenesis of this condition.3 here we present a case of digital pigmented sccis in a patient with history of immunosuppression secondary to chronic corticosteroid treatment for systemic sarcoidosis. this case highlights a unique association between inflammatory disease and development of pigmented sccis and emphasizes the importance of surveillance for atypical presentations of skin cancer in this patient population. abstract pigmented squamous cell carcinoma in-situ (sccis) is a rare variant of cutaneous scc that can clinically mimic malignant melanoma. this variant is more commonly seen in patients with brown and black skin and often presents in sun-protected areas. we report a case of a 38-year-old man with a dark brown, expanding lesion on the lateral aspect of the left middle finger and history of immunosuppression secondary to chronic corticosteroid treatment for systemic sarcoidosis. histologic examination of the lesion was consistent with a diagnosis of pigmented sccis. this report highlights a unique association between iatrogenic immunosuppression for inflammatory disease and development of pigmented sccis. additionally, the case emphasizes the importance of surveillance for pigmented scc in patients with skin of color, particularly those who may be at higher risk due to immunosuppression. introduction case report skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 407 a 38-year-old man presented with a fiveyear history of a dark brown, expanding lesion on the lateral aspect of the left middle finger. the patient’s constitutive skin color was brown. the lesion first appeared as a small, dark spot and had steadily enlarged in size. there was no associated pain, drainage, bleeding, or pruritis. the patient had no reported history of arsenic exposure or chronic scars or ulcers in the area. his past medical history was remarkable for systemic sarcoidosis, maintained on prednisone for three years after not tolerating a trial of mycophenolate mofetil. he quit smoking cigarettes six years prior and had a 3.5 pack year history. hiv screening was negative. on clinical exam there was an 8mm dark brown, irregularly shaped, keratotic papule with an eccentric area of lighter coloration on the radial aspect of the left third finger (figure 1). the clinical differential diagnosis included malignant melanoma and seborrheic keratosis. a shave biopsy was obtained. the histopathologic exam was notable for full-thickness epidermal atypia with prominent scattered mitotic figures throughout the epidermis. melanin pigment was present within the stratum corneum and epidermis (figure 2). in-situ hybridization staining for high-risk human papilloma virus (hpv) was negative. these features were consistent with a diagnosis of pigmented sccis. the patient subsequently underwent mohs micrographic surgery for removal of sccis. the lesion was removed in one stage and the wound was left to heal by secondary intention. the surgical site healed well with no evidence of recurrence at a 2-year follow up visit. figure 1. pigmented squamous cell carcinoma in-situ on the radial aspect of the left third finger figure 2. shave biopsy revealing full-thickness epidermal atypia, mitotic figures scattered throughout the epidermis, and melanin pigment within the stratum corneum and epidermis. a) h&e, 10x magnification, b) h&e, 20x magnification. a b skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 408 while skin cancer is more common in individuals with white skin, patients with brown and black skin account for 1-5% of all skin cancer cases, with scc being the most common skin cancer in this group.4 as illustrated in our case, patients with brown and black skin are more likely to have pigmented sccis in sun-protected areas, particularly acral surfaces.5 factors other than uv damage, including advanced age, immunosuppression, scars, burns, arsenic exposure, and/or hpv infection, may play a role in the pathogenesis of pigmented scc.6 the mean age of patients with pigmented sccis is approximately 63 years.3 a small number of cases of pigmented sccis have been documented in the pediatric population related to hpv, but cases in young adults, as in this case, are rare.5 cigarette smoking is a well-established risk factor for lung scc and mucosal head and neck scc, but there is inconsistent evidence on the association between smoking and development of cutaneous scc.7 in a recent meta-analysis, people who actively smoked were found to have an increased incidence of cutaneous scc, while people who previously smoked did not have the same increased risk.7 given our patient’s former smoking status and lack of other known risk factors, we hypothesize that his long-term corticosteroid therapy for systemic sarcoidosis may have played a role in the development of pigmented sccis at a young age. chronic immunosuppression significantly increases the risk of developing scc. patients who have undergone solid organ transplant and are on immunosuppressive therapy are 65 times more likely to develop scc than immunocompetent people.8 patients with hiv/aids also have an increased risk of developing scc, and there are case reports of pigmented sccis occurring in this population.9,10 risk of nonmelanoma skin cancer from immunosuppression for treatment of autoimmune or inflammatory disease is less well studied. patients with psoriasis who are treated with biologic agents, specifically tumor necrosis factor inhibitors, may have an increased risk of non-melanoma skin cancer.9 however, the relationship between corticosteroid-induced immunosuppression and risk of pigmented scc has not been studied. hpv infection is another proposed risk factor for development of pigmented sccis. hpv infection is recognized as a cause of sccis in the genital region11 and having a high-risk hpv serotype (specifically hpv 16 or 18) is thought to be an important risk factor for non-genital sccis, particularly on the digit.5,11 it has been hypothesized that the spread of hpv can occur from the genitals to the digits and that the nail matrix may serve as a reservoir for the hpv virus.11 however, there are cases of hpv-positive, digital pigmented sccis without a history of genital lesions.5 although it is not feasible to detect hpv in all cases of pigmented sccis due to high mutational burden in these lesions10, our patient had no known history of anogenital warts, penile cancer, or anal cancer and high-risk hpv testing was negative. while cases of pigmented sccis have been reported in transplant and hiv patients10,12, our case is unique in that it describes pigmented sccis in a patient with a history of immunosuppression secondary to prolonged corticosteroid use. although discussion conclusion skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 409 patients on certain immunosuppressants have been shown to be at higher risk for scc9, future studies are needed to examine the risk of corticosteroids and biologic agents on development of pigmented sccis. this case highlights the importance of including pigmented sccis on the differential for pigmented lesions in patients with skin of color. conflict of interest disclosures: none funding: none corresponding author: alaina j. james, md, phd university of pittsburgh medical center 3601 fifth avenue suite 5a pittsburgh pa, 15213 email: jamesaj@upmc.edu references: 1. ragi g, turner ms, klein le, stoll hl, jr. pigmented bowen's disease and review of 420 bowen's disease lesions. j dermatol surg oncol. jul 1988;14(7):765-9. doi:10.1111/j.1524-4725.1988.tb01161.x 2. cameron a, rosendahl c, tschandl p, riedl e, kittler h. dermatoscopy of pigmented bowen's disease. j am acad dermatol. apr 2010;62(4):597-604. doi:10.1016/j.jaad.2009.06.008 3. stewart tj, farrell j, crainic o, rosen rh. a large series of pigmented bowen's disease. int j dermatol. sep 2020;59(9):e316-e317. doi:10.1111/ijd.14977 4. hogue l, harvey vm. basal cell carcinoma, squamous cell carcinoma, and cutaneous melanoma in skin of color patients. dermatol clin. oct 2019;37(4):519-526. doi:10.1016/j.det.2019.05.009 5. rocha-méndez le, salazar-torres f, martínez-jaramillo b, tarango-martínez v, solís-ledesma g. an interdigital case of pediatric pigmented bowen's disease associated with human papillomavirus antibodies: a location not previously reported in this age group. jaad case rep. jul 2020;6(7):666-668. doi:10.1016/j.jdcr.2020.05.016 6. que skt, zwald fo, schmults cd. cutaneous squamous cell carcinoma: incidence, risk factors, diagnosis, and staging. j am acad dermatol. feb 2018;78(2):237-247. doi:10.1016/j.jaad.2017.08.059 7. pirie k, beral v, heath ak, et al. heterogeneous relationships of squamous and basal cell carcinomas of the skin with smoking: the uk million women study and meta-analysis of prospective studies. br j cancer. jul 2018;119(1):114-120. doi:10.1038/s41416-018-0105-y 8. herman s, rogers hd, ratner d. immunosuppression and squamous cell carcinoma: a focus on solid organ transplant recipients. skinmed. sep-oct 2007;6(5):2348. doi:10.1111/j.1540-9740.2007.06174.x 9. collins l, quinn a, stasko t. skin cancer and immunosuppression. dermatol clin. jan 2019;37(1):83-94. doi:10.1016/j.det.2018.07.009 10. fernández-sánchez m, charli-joseph y, domínguez-cherit j, guzman-herrera s, reyes-terán g. acral and multicentric pigmented bowen's disease in hiv-positive patients: report on two unusual cases. indian j dermatol. nov-dec 2018;63(6):506508. doi:10.4103/ijd.ijd_47_17 11. shimizu a, kuriyama y, hasegawa m, tamura a, ishikawa o. nail squamous cell carcinoma: a hidden high-risk human papillomavirus reservoir for sexually transmitted infections. j am acad dermatol. dec 2019;81(6):1358-1370. doi:10.1016/j.jaad.2019.03.070 12. serret ca, wang s, marsch a, hernandez c. pigmented squamous cell carcinoma presenting as longitudinal melanonychia in a transplant recipient. cutis. may 2018;101(5):375-377. neal bhatia,1 april armstrong,2 todd schlesinger,3 leon kircik,4 brian berman,5 mark lebwohl,4 darrel rigel,6 vishal a. patel,7 james del rosso,8 ayman grada,9 siva narayanan,10 ismail kasujee11 1therapeutics clinical research, san diego, ca; 2keck school of medicine, university of southern california, los angeles, ca; 3clinical research center of the carolinas, charleston, sc; 4icahn school of medicine, mount sinai, new york, ny; 5university of miami miller school of medicine, miami, fl; 6nyu grossman school of medicine, new york, ny; 7george washington school of medicine and health sciences, washington, dc; 8jdr dermatology research/thomas dermatology, las vegas, nv; 9department of dermatology, case western reserve university school of medicine, cleveland, oh; 10avant health llc, bethesda, md; 11almirall sa, barcelona, spain. an expert panel questionnaire (epq) for assessing patient-reported and clinician-reported outcomes in actinic keratosis presented at fall clinical dermatology conference, 2022 – october 19-23, 2022 – las vegas, nv • timely, effective treatment of actinic keratoses (aks) is important because there is no reliable way to predict which of these hyperkeratotic lesions on chronically sun-exposed skin will become cancerous.1,2 • some topical treatments for aks such as 5-fluorouracil and imiquimod are associated with uncomfortable and visible local skin reactions (lsrs), which have been linked to poor treatment tolerability and low treatment satisfaction.3,4 • clinical trials of ak have not typically included patient-reported outcomes (pros). • ak treatment-related factors such as skin reactions are known to impact qol and treatment adherence.5 • current assessments on topical treatment attributes in ak do not evaluate safety, effectiveness, and satisfaction from both clinician and patient perspectives, creating an unmet need for more comprehensive ak-specific measures that fully capture the patient experience.3,6,7 • an ak-specific pro instrument may help highlight patient centric issues and outcomes in clinical studies and real-world clinical practices. • comparing current and previous ak treatments would be useful in gauging the relative impact of different treatments. further, simultaneously assessing pros and clinician reported outcomes (clinros) on treatment attributes may enhance clinician-patient communication, providing great utility among clinical practitioners.7 background 1. balcere a, rone kupfere m, čēma i, krūmiņa a. medicina (kaunas). 2019;55(4); 2. rosso jd, armstrong aw, berman b, et al. j drugs dermatol. 2021;20(8):888-893; 3. khanna r, bakshi a, amir y, goldenberg g. clin cosmet investig dermatol. 2017;10:179-184; 4. emmerich vk, cull d, kelly ka, feldman sr. journal of dermatological treatment. 2022 may 19;33(4):2075-8; 5. kasujee i., diaz gallo c, jose lambert c, massana montejo e, narayanan s. paper presented at: ispor; may 15-18, 2022, 2022; washington, dc; 6. criscione vd, weinstock ma, naylor mf, luque c, eide mj, bingham sf. cancer. 2009;115(11):2523-2530; 7. marson j, rosso j, bhatia n, rigel d. skin the journal of cutaneous medicine. 2021;5:83-89. sponsored by almirall, s.a. references conclusions the newly developed epq may address important gaps in the existing pro measures and help elicit patient-centric, ak-specific outcomes from patients and their clinicians and help optimize ak management and enhance patient outcomes. objective • to create an expert panel questionnaire (epq) comprising of ak-specific pros and clinros for use in research studies and clinical practices. results • the panel discussed nine pros encompassing cosmetic outcomes (‘overall appearance of the skin’, ‘ability to improve how skin looks’, ‘ability to improve skin texture’), effects of local skin reactions (‘compared to previous topical treatment experience’, relative rating of ‘duration of skin reactions’, ‘severity of skin reactions’, impact on your daily activities’), relative convenience/ease of use of new treatment, overall satisfaction with new treatment, and likelihood of future use. • two clinros encompassing physician global assessment (pga) of ak and severity of skin photodamage were also reviewed. • the panel suggested wording changes to pros and clinros as outlined in table 1. • for subjects re-treated with another topical treatment at week-24, questions 3-8 are reworded to enable the assessment of relative satisfaction associated with tirbanibulin in comparison to the ‘most recent topical treatment for ak’. • the clinician version of the questions 1-9 were worded to refer to clinician experience / observation of tirbanibulin effects among their patients. • following refinement of epqs, panelists unanimously (100%) achieved consensus in approving each of the 11 epq items. • panelists also suggested using the nine pros as clinros to gather patient-experience from both patient and clinician perspective on identified domains. methods • a 9-person consensus panel of dermatologists with expertise in the treatment of aks was virtually convened using a two-step modified delphi method to establish consensus on epq items. • input from ak patient interviews and targeted literature reviews was used to identify 11 epq items. • in first round, epq items were distributed to the panel for discussion of each item and solicit comments individually and collectively. • in the second round, the panel refined epq items which were distributed for feedback and approval. table 1. expect panel deliberations on epq domain question edits from round 1 finalized epq cosmetic outcomes 1 changed from “treated area” to “original ak treated area” and added definition of “original ak treated area”. same change was made to all relevant epq items. compared to x weeks ago, how has the overall appearance of your skin in the original ak treated area changed? (scale: 1-5; much worsened much improved) note: the “original treated area” is the skin area with ak that was treated with treatment y at beginning of this study. 2 updated scale from “0-4; not satisfied – completely satisfied” to 1-7; extremely dissatisfied – extremely satisfied) how satisfied are you with this treatment’s ability to improve how your skin looks (example: reduced redness, discoloration, crusting, scaling) in the original ak treated area? (scale: 1-7; extremely dissatisfied – extremely satisfied) 3 added description for skin texture. changed scale from “(0-4; not satisfied – completely satisfied)” to (1-7; extremely dissatisfied – extremely satisfied) how satisfied are you with this treatment’s ability to improve your skin texture (ie, how your skin feels in terms of roughness, bumpiness, scaliness) as a result of the treatment in the original ak treated area? (scale: 1-7; extremely dissatisfied – extremely satisfied) future preferences 4 no change to the question. updated scale from “0-4; very unlikely – very likely” to “1-5; very unlikely – very likely.” in case you need to be retreated for ak, how likely are to you consider treatment y again? (scale: 1-5; very unlikely – very likely) 5 added “considering the factors such as convenience / ease of use, duration and severity of skin reactions, impact on daily life, etc.” describing satisfaction. changed scale from “(0-4; much worse – much better) to (1-5; much worse much better) if patient has used a topical treatment in the past: compared to your previous experience with topical treatment x for ak, how would you rate your overall satisfaction (considering the factors such as convenience / ease of use, duration and severity of skin reactions, impact on daily life, etc.) with treatment y? (scale: 1-5; much worse – much better) effect of lsrs 6 added description for duration of skin reactions. if patient has used a topical treatment in the past: compared to your previous experience with topical treatment x for ak, how would you rate the duration of skin reactions (i.e., how long the skin reactions lasted) associated with treatment y in the original ak treated area: (scale: 1-5; much longer – much shorter) much shorter much longer with tirbanibulin 7 new question added. if patient has used a topical treatment in the past: compared to your previous experience with topical treatment x for ak, how would you rate the severity of skin reactions (i.e., how bad the skin reactions were) associated with treatment y in the original ak treated area (scale: 1-5; much worse – much better) 8 updated description of daily activities from “(such as shopping, bathing, social engagements, activities, etc) “ to (i.e., ability to carry out shopping, bathing, social engagements, scheduling vacations, outdoor activities, activities at work, attendance at work, etc.) if patient has used a topical treatment in the past: compared to your previous experience with treatment x, how would you rate the impact on your daily activities (i.e., ability to carry out shopping, bathing, social engagements, scheduling vacations, outdoor activities, activities at work, attendance at work, etc.) due to skin reactions associated with treatment y use in the original ak treated area? (scale: 1-5; much worse – much better) 9 new question added. if patient has used a topical treatment in the past: compared to your previous experience with topical treatment x for ak, how would you rate the convenience/ease of use (such as frequency of use, easy to follow instructions, comfortable at apply, etc.) associated with treatment y? (scale: 1-5; much worse – much better) pga (ak) 10* ak lesion clearance levels were added to the response scale. overall, how is your patient’s ak in the original treated area right now? (scale: 0-4: not cleared, minimally cleared [≥5%-49%], partially cleared [≥50%-74%], almost cleared [≥75%-99%], cleared [100%]) photodamage severity assessment 11* changed from “rate the severity” to “rate the current severity”. added description on photodamage. how do you rate the current severity of skin photodamage in the original ak treated area? note: photodamage can be described as alterations in the structure, function, and appearance of the skin as a result of prolonged or repeated exposure to ultraviolet (uv) radiation from the sun or other uv sources. (scale: 0-3; absent – severe) 0: absent smooth evenly pigmented skin 1: mild freckling and/or other dyspigmentation 2: moderate above plus mildly rough “dry” skin, fine wrinkling and/or telangiectasias or blotchy erythema 3: severe above plus pronounced “dryness” and/or dyspigmentation and/or telangiectasia or erythema, and/or wrinkling, with or without areas of actinic purpura *clinros, answered only by clinicians; lsrs (local skin reactions), pga (physician global assessment) results these outcomes could facilitate a comparison of pros with clinros on treatment attributes and may enhance clinician-patient communication, providing great utility among practitioners.10 objective to assess the continual maintenance of week 16 responses with bimekizumab (bkz) versus secukinumab (sec) treatment at every visit to week 48 in patients with moderate to severe plaque psoriasis. introduction • bkz is a monoclonal igg1 antibody that selectively inhibits interleukin (il)-17f in addition to il-17a, whilst sec is a widely used monoclonal igg1 antibody that targets il-17a.1 • be radiant (nct03536884) was the first phase 3 study to compare inhibition of il-17a and il-17f with inhibition of il-17a alone. • patient surveys have confirmed that maintaining a long-lasting response is a key treatment goal for patients who have already achieved skin clearance.2,3 materials and methods • be radiant is a phase 3b, randomized trial, consisting of a 48-week double-blinded, active comparator-controlled period followed by an ongoing open-label extension (figure 1).4 patients who did not enter the open-label extension entered a safety follow-up period. • this analysis includes patients who achieved a psoriasis area and severity index (pasi) of ≤2 (a key treat-to-target objective)5 or 0 (complete skin clearance) at week 16 and continued to receive study medication at week 16 or later, reported with bkz dose groups pooled. • we report the proportion of responders who continued to achieve their response at every study visit up to and including week 48, as well as pasi=0 responders who maintained pasi ≤1 or pasi ≤2. • missing data are primarily accounted for using modified non-responder imputation (mnri), whereby patients with missing data at a given week following discontinuation due to lack of efficacy or due to an adverse event were considered non-responders at subsequent visits; all other missing data were imputed using multiple imputation methodology. • supporting analyses are also reported: – observed case (oc): missing data is discounted in the consideration of continuous maintenance of response. – nri: patients with missing data at a given week are considered non-responders from that timepoint onwards. results • at baseline, 373 patients were randomized to bkz, and 370 were randomized to sec. • at week 16, 230/373 (61.7%) bkz-randomized and 181/370 (48.9%) sec-randomized patients achieved pasi=0, whilst 318/373 (85.3%) bkz-randomized and 283/370 (76.5%) sec-randomized patients achieved pasi ≤2. • baseline demographics and characteristics were largely consistent across both randomization arms for pasi=0 and pasi ≤2 responders, although the overall population of bkz-randomized patients, as well as week 16 pasi=0 and pasi ≤2 responders, had higher baseline disease severity as measured via the investigators global assessment (iga) compared with sec-randomized patients (table 1). • pasi=0 was continuously maintained through week 48 by 63.7% bkz-treated and 54.3% sec-treated week 16 responders (table 2). – among week 16 pasi=0 responders, pasi ≤2 was continuously maintained at each study visit through weeks 16–48 by 93.0% of bkz-treated and 87.4% of sec-treated patients. • pasi ≤2 was continuously maintained at each study visit through weeks 16–48 by 88.0% bkz-treated and 79.1% sec-treated week 16 responders (table 2). • rates for both pasi=0 and pasi ≤2 response maintenance were consistent when using nri and oc imputation (table 2). summary presented at the 42nd annual fall clinical dermatology conference | las vegas, nv | october 20–23, 2022 conclusions a higher proportion of bkz-randomized patients achieved pasi=0 and pasi ≤2 at week 16, compared with sec-randomized patients. of the bkz-randomized pasi=0 week 16 responders, 93.0% continuously maintained disease control. a higher proportion of bkz-randomized patients compared with sec-randomized patients also maintained pasi ≤2 response at every single visit. r.b. warren,1 c. conrad,2 p. foley,3 l. iversen,4 r.g. langley,5 g. kokolakis,6 l. davis,7 v. vanvoorden,8 s. wiegratz,9 j.f. merola10 bimekizumab versus secukinumab continuous maintenance of response at every visit through one year in patients with moderate to severe plaque psoriasis: post-hoc results from the be radiant phase 3b trial previously presented at spin 2022 institutions: 1dermatology centre, salford royal nhs foundation trust, manchester nihr biomedical research centre, the university of manchester, manchester, uk; 2department of dermatology, university hospital lausanne, lausanne, switzerland; 3the university of melbourne, st. vincent’s hospital melbourne, fitzroy and probity medical research inc. skin health institute, carlton, victoria, australia; 4department of dermatology, aarhus university hospital, aarhus, denmark; 5dalhousie university, halifax, nova scotia, canada; 6psoriasis research and treatment center, charité – universitätsmedizin berlin, berlin, germany; 7ucb pharma, raleigh, nc, usa; 8ucb pharma, brussels, belgium; 9ucb pharma, monheim, germany; 10harvard medical school, brigham and women’s hospital, boston, massachusetts, usa. references: 1papp ka et al. j am acad dermatol 2018;79:2; 2tada y et al. j dermatol 2021;48:1665–74; 3rasmussen mk et al. acta derm venereol 2019;99:158–63; 4reich k et al. n engl j med 2021;385:142–52; 5mahil sk et al. br j dermatol 2020;182:1158–66. author contributions: substantial contributions to study conception/design, or acquisition/analysis/interpretation of data: rbw, cc, pf, li, rgl, gk, ld, vv, sw, jfm; drafting of the publication, or revising it critically for important intellectual content: rbw, cc, pf, li, rgl, gk, ld, vv, sw, jfm; final approval of the publication: rbw, cc, pf, li, rgl, gk, ld, vv, sw, jfm. author disclosures: rbw: consulting fees from abbvie, almirall, amgen, arena, astellas, avillion, biogen, bristol myers squibb, boehringer ingelheim, celgene, eli lilly, gsk, janssen, leo pharma, novartis, pfizer, sanofi and ucb pharma; research grants to his institution from abbvie, almirall, janssen, leo pharma, novartis and ucb pharma; honoraria from astellas, dice, gsk and union. cc: consultant and/or principal investigator in clinical trials for: abbvie, actelion, amgen, almirall, boehringer ingelheim, bristol myers squibb, celgene, eli lilly, galderma, incyte, janssen-cilag, leo pharma, msd, novartis, pfizer, samsung, sanofi genzyme and ucb pharma. pf: institution received grant support from abbvie, amgen, celgene, eli lilly, galderma, janssen, leo pharma, merck, novartis, pfizer, sanofi and sun pharma; investigator for abbvie, akaal, amgen, arcutis, argenx, aslan, astrazeneca, bristol myers squibb, boehringer ingelheim, botanix, celgene, celtaxsys, csl, cutanea, dermira inc., eli lilly, galderma, genentech, geneseq, gsk, hexima, janssen, leo pharma, medimmune, merck, novartis, pfizer, regeneron, reistone, roche, sanofi, sun pharma, ucb pharma and valeant; served on the advisory board for abbvie, amgen, aslan, bristol myers squibb, boehringer ingelheim, celgene, eli lilly, galderma, gsk, hexima, janssen, leo pharma, mayne pharma, merck, novartis, pfizer, sanofi, sun pharma, ucb pharma and valeant; consultant for aslan, bristol myers squibb, eli lilly, galderma, hexima, janssen, leo pharma, mayne pharma, medimmune, novartis, pfizer, roche, ucb pharma and wintermute; received travel grants from abbvie, eli lilly, galderma, janssen, leo pharma, merck, novartis, pfizer, roche, sanofi, and sun pharma; speaker for or received honoraria from abbvie, amgen, celgene, eli lilly, galderma, gsk, janssen, leo pharma, merck, novartis, pfizer, roche, sanofi, sun pharma, ucb pharma, and valeant. li: consultant and/or paid speaker for and/or participated in clinical trials sponsored by abbvie, almirall, amgen, astrazeneca, bristol myers squibb, boehringer ingelheim, celgene, eli lilly, janssen, leo pharma, msd, novartis, pfizer, regranion, samsung-bioepis, ucb pharma and union therapeutics. rgl: principal investigator for abbvie, amgen, boehringer ingelheim, celgene, eli lilly, leo pharma, merck, novartis, pfizer and ucb pharma; served on scientific advisory boards for abbvie, amgen, boehringer ingelheim, celgene, eli lilly, leo pharma, merck, novartis, pfizer and ucb pharma; provided lectures for abbvie, amgen, celgene, eli lilly, leo pharma, merck, novartis and pfizer. gk: received travel grants or honoraria, or has been a consultant member of advisory boards and speakers bureaus or has served as investigator for abbvie, actelion, basilea, biogen, boehringer ingelheim, celgene, hexal-sandoz, janssen-cilag, leo pharma, eli lilly, msd, novartis, pfizer and ucb pharma. ld, vv, sw: employee and shareholder of ucb pharma. jfm: jfm has been a consultant for abbvie, amgen, bayer, biogen, bristol myers squibb, celgene, eli lilly, janssen, novartis, pfizer, sanofi-regenero and ucb pharma; principal investigator for dermavant, leo pharma and ucb pharma. acknowledgements: this study was funded by ucb pharma. we thank the patients and their caregivers in addition to the investigators and their teams who contributed to this study. the authors acknowledge susanne wiegratz, msc, ucb pharma, monheim, germany, for publication coordination, natalie nunez gomez, md, ucb pharma, monheim, germany, for critical review, emma francis-gregory, ba, costello medical, cambridge, uk, for medical writing and editorial assistance and the design team, costello medical, uk, for graphic design assistance. figure 1 study design table 2 proportion of week 16 responders maintaining responses at every single visit through week 48 bkz: bimekizumab; bsa: body surface area; ci: confidence interval; dlqi: dermatology life quality index; iga: investigator’s global assessment; il: interleukin; mnri: modified non-responder imputation; nri: non-responder imputation; nsub: number of patients with a non-missing measurement; oc: observed case; pasi: psoriasis area and severity index; q4w: every 4 weeks; q8w: every 8 weeks; sec: secukinumab; sd: standard deviation. table 1 baseline characteristics bkz-randomized patients sec-randomized patients all patients (n=373) pasi=0 responders (n=230) pasi ≤2 responders (n=318) all patients (n=370) pasi=0 responders (n=180) pasi ≤2 responders (n=281) age (years), mean ± sd 45.9 ± 14.2 45.8 ± 13.8 45.3 ± 13.9 44.0 ± 14.7 42.8 ± 14.5 43.0 ± 14.4 male, n (%) 251 (67.3) 156 (67.8) 212 (66.7) 235 (63.5) 110 (61.1) 177 (63.0) caucasian, n (%) 347 (93.0) 215 (93.5) 298 (93.7) 348 (94.1) 169 (93.9) 266 (94.7) weight (kg), mean ± sd 90.1 ± 21.3 88.0 ± 20.9 89.0 ± 21.4 88.8 ± 20.0 86.4 ± 19.7 87.3 ± 19.6 duration of psoriasis (years), mean ± sd 18.4 ± 13.1 18.8 ± 13.1 18.0 ± 12.7 17.2 ± 12.3 16.9 ± 12.0 17.0 ± 12.0 pasi, mean ± sd 20.2 ± 7.5 19.8 ± 7.3 20.0 ± 7.5 19.7 ± 6.7 19.7 ± 6.6 19.4 ± 6.2 bsa (%), mean ± sd 24.8 ± 15.5 23.7 ± 14.7 24.4 ± 15.4 23.8 ± 14.3 23.8 ± 14.3 23.1 ±13.3 iga, n (%) 3: moderate 240 (64.3) 154 (67.0) 211 (66.4) 268 (72.4) 136 (75.6) 214 (76.2) 4: severe 131 (35.1) 76 (33.0) 105 (33.0) 102 (27.6) 44 (24.4) 67 (23.8) dlqi, mean ± sd 10.8 ± 6.6 11.0 ± 6.7 11.0 ± 6.6 11.3 ± 7.2 10.8 ± 6.8 11.3 ± 7.1 any prior systemic therapy, n (%) 267 (71.6) 164 (71.3) 225 (70.8) 272 (73.5) 134 (74.4) 206 (73.3) any prior biologic therapy, n (%) 125 (33.5) 76 (33.0) 109 (34.3) 119 (32.2) 57 (31.7) 87 (31.0) bkz-randomized patients sec-randomized patients mnri, % (95% ci) nri, % (n/n) oc, % (n/nsub) mnri, % (95% ci) nri, % (n/n) oc, % (n/nsub) week 16 pasi=0 responders maintaining: pasi=0 63.7 (57.3, 70.0) 60.4 (139/230) 65.0 (139/214) 54.3 (46.9, 61.7) 51.7 (93/180) 55.7 (93/167) pasi ≤1 83.6 (78.7, 88.4) 74.3 (171/230) 79.9 (171/214) 74.9 (68.4, 81.4) 65.6 (118/180) 70.7 (118/167) pasi ≤2 93.0 (89.7, 96.3) 82.6 (190/230) 88.8 (190/214) 87.4 (82.5, 92.3) 72.8 (131/180) 78.4 (131/167) week 16 pasi ≤2 responders maintaining: pasi ≤2 88.0 (84.4, 91.5) 76.7 (244/318) 82.4 (244/296) 79.1 (74.3, 83.9) 64.4 (181/281) 70.7 (181/256) week 0 (baseline) week 48 2–5 weeks sec 300 mg q4wa n=370 bkz 320 mg q4w n=373 n=215 n=147 n=743 1:1 randomization week 16 bkz 320 mg q4w bkz 320 mg q8w screening initial treatment period maintenance period we report the proportions of patients who continuously maintained their response from week 16 through week 48 61.7% (230/373) of bkz-randomized patients achieved pasi=0 at week 16 (nri) response at every single study visit week 16 response week 48 63.7% of bkz week 16 pasi=0 responders continually maintained pasi=0 response to week 48 (mnri) 85.3% (318/373) of bkz-randomized patients achieved pasi ≤2 at week 16 (nri) 88.0% of bkz week 16 pasi ≤2 responders continually maintained pasi ≤2 response to week 48 (mnri) 61.7% 85.3% asec 300 mg was administered at baseline, weeks 1, 2, 3 and 4, then q4w for the remainder of the double-blinded treatment period. at week 48, patients entered the open-label extension, or entered the safety follow-up period. skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 429 brief article assessing patient reported quality of care and safety in mohs surgery during the covid-19 pandemic jesalyn a. tate, md1, jennifer wang, ba1, shreya patel, md2, rajiv i. nijhawan, md1, divya srivastava, md1 1 department of dermatology, university of texas southwestern medical center, dallas, tx 2 department of dermatology, boston university medical center, boston, ma the sars-cov-2 coronavirus (covid-19) has impacted care across all fields of medicine, including mohs micrographic surgery (mms). a survey of mohs surgeons in the uk reported impacts of covid-19 on mms, with 49% cessation of mms in the early months of the pandemic1. another study demonstrated a low risk of contracting covid during outpatient surgery when utilizing appropriate precautions2. the dermatologic surgery clinic at our institution implemented patient safety protocols during the pandemic, considering published guidelines and cdc recommendations3,4. this includes masking, increased ppe, preoperative covid testing for treatment around the nose and mouth, etc. we also increased the use of dissolvable sutures and utilized patient portal messaging and/or telehealth. it is important to better to understand patients’ experiences with care during the pandemic. the study’s objective is to assess patient-reported quality of care and sense of safety while receiving mms during the pandemic, identify factors that abstract covid-19 has greatly impacted patients’ ability to receive medical care. early on during the pandemic, skin cancer diagnosis and treatment were often delayed due to fear of viral spread. in certain locales, executive orders have prevented physicians from performing procedures that were not immediately lifesaving. this study aims to assess patient-reported quality of care and sense of safety while receiving mohs micrographic surgery (mms) during the pandemic. the intent of this study is to identify patient-specific factors that influence concerns and feelings of safety, and thus guide future safety measures. a telephone survey was administered to assess patient concerns about treatment delay, feelings of safety, and satisfaction. a retrospective chart review was performed to collect demographics, comorbidities, tumor characteristics, etc. a total of 144 patients (102 male, 42 female; average 71.9 years old) completed the study. overall, patients felt safe and satisfied, with 75.7% reporting 10/10 safety (average 9.5/10) and 84% reporting 10/10 satisfaction (average 9.7/10). patients had more notable levels of concern regarding pandemic-related treatment delays (median 2/10), compared to the risk of contracting covid during their visit (median 1/10). concerns regarding treatment delay included an increase in cancer size, spread, pain, and scarring. this study demonstrates that high levels of patient feelings of safety and satisfaction can be obtained with mms during the pandemic. as the pandemic continues, it is imperative that patients can receive high quality and timely care without compromising safety. outpatient dermatologic surgery can continue without jeopardizing patients' overall feeling of safety and satisfaction. introduction skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 430 influence feelings of safety, and guide future safety measures. this study received irb approval from the university of texas southwestern (utsw). this study included patients treated with mms at the utsw dermatologic surgery clinic from march 16, 2020 to june 30, 2020. patients referred for outside repair or who received mohs for >1 skin cancer on the same date or on >1 occasion during the study period were excluded. 277 patients met inclusion criteria and 144 patients (102 male, 42 female) participated. all patients were contacted via telephone, and data collection was performed between august 28, 2020 and november 16, 2020. survey data included patient satisfaction, treatment concerns (i.e. bleeding, pain, etc.), surgery delay concerns, fears of contracting covid-19, and additional precautions patients feel could improve safety. patients were asked to rate responses on a 10-point scale. the second aspect of the study was a retrospective chart review gathering patient age, sex, immunosuppression, history of prior mms at utsw, tumor type, size, location, number of stages, method of repair, and use of telehealth and/or patient portal messaging. statistical analysis domains of level of concern were assessed using median and interquartile ranges as the data was significantly skewed. demographic, clinicopathologic, and treatment characteristics were compared between the groups who felt satisfied or safe as compared to those who did not using chisquared analyses or t-tests, where appropriate. univariate logistic regression was used to assess if the variables were significantly associated with the odds of feeling completely safe or satisfied. statistical significance was set at p<0.05. all analyses were completed using spss version 24 (ibm armonk, ny). outcome measures the first outcome measure was to determine feelings of safety. the second outcome measure was to determine if demographic, health, or tumor related factors influenced feelings of safety. overall, patients felt safe and satisfied, with 75.7% of patients reporting 10/10 safety and 84% reporting 10/10 satisfaction. patients reported higher levels of concern regarding treatment delays because of the pandemic over contracting covid-19 (table 1). a total of 86/111 (77.5%) patients with sutured wounds had dissolvable sutures and 97.7% (84/86) reported being satisfied with not having to return for suture removal. of those that required follow-up, 22.4% utilized telehealth and 100% were satisfied with this. patients who felt completely safe were less likely to receive dissolvable sutures than those who did not feel completely safe (73.0% vs. 95.5%, p=0.024). there were no other significant differences between demographic, clinicopathologic, or treatment characteristics regarding safety or satisfaction (table 2). however, on logistic regression, the use of dissolvable suture appeared to be negatively related with feelings of safety, but this relationship fell just short of significance (or=0.13, p=0.051) (table 3). design & methods results skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 431 table 1. level of concern and safety results from the survey and telephone encounters skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 432 table 2. demographic and surgical differences between patients who felt completely vs. not completely safe and satisfied skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 433 *patients with secondary intention healing excluded (n=33) **patients receiving dissolvable sutures excluded (n=86) table 2 continued. skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 434 table 3. demographic and surgical differences between patients who felt completely vs. not completely safe and satisfied skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 435 skin cancer is the most common type of cancer in the united states, so delays in treatment impact a substantial number of patients, potentially leading to an increase in cancer size, pain, and/or risk of metastasis5,6. while postponing non-urgent treatment was initially helpful to slow viral spread, the pandemic has continued with repeated intermittent spikes in case numbers. therefore, it is critical to continue the treatment of skin cancers with safety precautions that allow physicians to provide adequate and safe care. a recent study at an academic center in new york city detailed their implemented safety precautions to prevent transmission of covid-19 in 262 excision cases7. this study, along with the other resources available, can serve as guides to facilitate adopting safety protocols for treatment during the pandemic. with the utilization of clinic safety protocols, we found that patients’ fears regarding delays in skin cancer treatment outweighed fears of contracting covid-19. these findings are comparable to other survey results of patients receiving mms in the uk during the pandemic8. in this study, patients who did not feel completely safe were more likely to have received dissolvable sutures. while it is possible receiving dissolvable sutures could contribute to unsafe feelings for unclear reasons, it is more probable that patients who felt less safe were more likely to opt for having dissolvable sutures to avoid additional office visits. additionally, most patients that required a follow up visit had an in-person visit. while this may partly depend on the nature of their repair or unfamiliarity with telehealth technology, it also suggests that patients may also feel comfortable with in-person visits if appropriate safety protocols are in place. limitations of the study include evaluating patients at only a single center, possible recall bias due to the study’s retrospective nature, and limitations of patient survey response rate. covid-19 has greatly impacted patients’ ability to receive medical care, sometimes leading to delays in diagnosis and treatment. although, prior to their visit, several patients expressed some degree of concern regarding skin cancer treatment during covid-19, most patients reported feeling safe during their appointment and satisfied with their care. these findings support that skin cancer treatment during the pandemic is well-received by patients. as the pandemic continues or new health crises arise, outpatient dermatologic surgery can continue to operate without compromising patients’ perception of safety if sufficient safety protocols that address patients’ concerns are implemented. conflict of interest disclosures: none funding: none corresponding author: divya srivastava, md 5939 harry hines blvd, 4th floor dallas, tx 75390 phone: 214-645-8950 email: divya.srivastava@utsw.edu references: 1. nicholson p, ali fr, patalay r, craythorne e, mallipeddi r. patient perceptions of mohs micrographic surgery during the covid‐19 pandemic and lessons for the next outbreak. discussion conclusion skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 436 clinical and experimental dermatology. 2021 jan;46(1):179-80. 2. miranda bh, jica rci, pinto-lopes r, et al. st andrew's covid-19 surgery safety (stacs) study: skin cancer [published online ahead of print, 2021 feb 19]. j plast surg hand surg. 2021;1-7. 3. der sarkissian sa, kim l, veness m, yiasemides e, sebaratnam df. recommendations on dermatologic surgery during the covid-19 pandemic. j am acad dermatol. 2020;83(1):e29e30. 4. yuan jt, brian si. urgent safety considerations for dermatologic surgeons in the covid-19 pandemic. dermatology online journal. 2020;26(8). 5. siegel rl, miller kd, jemal a. cancer statistics, 2020. ca cancer j clin. 2020;70(1):7-30. 6. baumann bc, macarthur km, brewer jd, et al. management of primary skin cancer during a pandemic: multidisciplinary recommendations. cancer. 2020;126(17):3900-3906. 7. tee mw, stewart c, aliessa s, et al. dermatologic surgery during the covid-19 pandemic: experience of a large academic center. j am acad dermatol. 2021;84(4):10941096. 8. nicholson p, ali fr, mallipeddi r. impact of covid‐19 on mohs micrographic surgery: uk‐ wide survey and recommendations for practice. clinical and experimental dermatology. 2020 oct;45(7):901-2. background � plaque psoriasis is a chronic, inflammatory, immune-mediated skin disorder that negatively impacts a patient’s quality of life, both physically and psychologically1,2 � in individuals with a genetic predisposition, environmental factors (eg physical and psychological stress) may trigger the initiation of psoriasis, beginning with the activation of dendritic cells (figure 1)1,3 � topical treatments containing corticosteroids and vitamin d analogues target key steps in psoriasis pathogenesis and are essential, well-established first-line treatments for patients with mild-to-moderate psoriasis4,5 � here we discuss recent data showing the anti-inflammatory and immunomodulatory mechanisms underlying the efficacy of fixed-dose combination therapy versus topical steroidal monotherapy, and explore developments in topical drug delivery and the clinical relevance of these data tnf-α il-12 tnf-α and ifn-γ il-17 and il-22 cytokines, chemokines and amps il-23 type 1 t-cell differentiation and activation keratinocyte hyperproliferation and abnormal differentiation psoriatic plaque formation dendritic cell activation type 17 t-cell differentiation and activation figure 1. key steps in the psoriasis pathogenesis loop arrows indicate pro-inflammatory mediator release. amp, antimicrobial peptide; il, interleukin; ifn, interferon; tnf, tumour necrosis factor corticosteroid and vitamin d analogue combination treatment addresses therapeutic goals, resulting in increased effectiveness versus monotherapy � the treatment goal is to clear the psoriatic plaques by inhibiting the underlying inflammation via immunomodulation (rather than immunosuppression), thereby normalizing skin homeostasis, keratinocyte proliferation and differentiation � both corticosteroids and vitamin d analogues inhibit pro-inflammatory mediator release (figure 1) from dendritic cells, type 1 and 17 (cytotoxic and helper) t-cells, and keratinocytes.6–9 vitamin d analogues exert normalizing effects on the hyperproliferation and abnormal differentiation of keratinocytes and also have immunomodulatory effects6,10 � recent preclinical data show that fixed-dose combination treatment provides significantly increased inhibition of pro-inflammatory cytokines compared with monotherapies (figure 2)11 � the effect of fixed-dose combination therapy on cellular targets in psoriasis pathophysiology is summarized in figure 3a–d corticosteroid and vitamin d analogue combination topical treatment may provide long-term management of psoriasis � upon clearance of psoriatic plaques and normalization of skin homeostasis, the therapeutic objective shifts to the maintenance of a relapse-free state as psoriatic inflammation tends to recur in previously affected skin locations12,13 – this may be caused by the expression of inflammatory cytokines upon reactivation of immune cells present in the apparently normalized, plaque-free skin after treatment12,13 � new data indicate that combination treatment is able to induce regulatory t-cells, as well as counteract the activation and differentiation of cytotoxic t-cells, more effectively than corticosteroids alone (figure 3e)11 – for example, topical steroid monotherapy can suppress immunomodulatory type 2 helper t-cells, while combination treatment can prevent this by increasing the release of immunomodulatory cytokines, eg il-10 (figure 2)11 � further clinical studies are required to explore the possibility of fixed-dose combination treatment for the long-term management of psoriasis 0 20 40 60 80 il-17a secretion from t-cells† cal bd combinationcal bd combination cal bd combination cal bd combination 0 20 40 60 80 0 50 100 150 200 250 300 350 0 20 40 60 80 il-10 secretion from t-cells il-23 secretion from dcs* il8 secretion from kcs‡ % o f c on tr ol % o f c on tr ol % o f c on tr ol % o f c on tr ol p≤0.01 ns p<0.001 p<0.001 p<0.001 p<0.001 p<0.001 p<0.001 figure 2. combination treatment in vitro is significantly more effective than monotherapies in inhibiting cytokines released from key cells involved in psoriasis pathogenesis levels of pro-inflammatory (il-23, il-17a and il-8) and immunomodulatory (il-10) cytokines released by dcs, t-cells, and kcs are expressed as percentage of vehicle-treated control (100%).11 treatment was applied before dc activation, after (il-17a) and before (il-10) th-cell differentiation, and on stimulated kcs.11 *combination treatment also led to tnf-α inhibition (both p<0.001); †similar results were found for the inhibition of il-22, il-8, and tnf-α (all p<0.001); ‡similar results were observed for il-6, il-17c, and il-20 (all p<0.001). bd, betamethasone dipropionate; cal, calcipotriol; dc, dendritic cell; il, interleukin; kc, keratinocyte; ns, not significant; th, t-helper cell; tnf, tumour necrosis factor figure 3. summary of the complementary and additive actions of corticosteroid and vitamin d analogue combination treatment on cellular targets in the pathophysiology of psoriasis panels (a) to (d) represent therapeutic targets for inhibiting the pro-inflammatory environment. panel (e) corresponds to the possible key targets for long-term maintenance therapy. plus and minus signs indicate induction and inhibition, respectively. *resting and naïve dcs and t-cells. dc, dendritic cell; il, interleukin; tc, cytotoxic t-cell; th, t-helper cell; tnf, tumour necrosis factor; t-reg, regulatory t -cell clinical benefits of corticosteroid and vitamin d analogue fixed-dose combination treatment � corticosteroids and vitamin d analogues are directed at different targets in psoriasis pathogenesis. their complementary and additive effects observed in preclinical data have translated into clinically effective fixed-dose combination therapies, as supported by randomized, double-blind, controlled clinical studies14,15 � for example, fixed-dose combination calcipotriol (cal)/betamethasone dipropionate (bd) aerosol foam was significantly more efficacious in improving mean modified psoriasis area and severity index (mpasi; excluding the head, which was not treated) score than the individual active ingredients after 4 weeks (p<0.001 versus both cal foam and bd foam)14 combination therapy attenuates side effects associated with their individual monotherapies � long-term continuous use of topical corticosteroids and vitamin d analogue monotherapy is associated with increased risk of skin atrophy and perilesional skin irritation, respectively (table 1)5,9,16 – recent studies in cultured skin cells demonstrated that the addition of cal reduces early signs of betamethasone-induced skin atrophy by modulating key extracellular matrix components17 – a 52-week clinical study demonstrated that daily treatment with cal/bd ointment significantly reduced the overall number of adverse events – particularly burning, itching, and erythema of skin – compared with vitamin d analogue monotherapy (cal ointment, 50 µg/g)18 table 1. summary of the effects of corticosteroids and vitamin d analogues in skin atrophy17,19,20 mechanism effect of corticosteroids effect of vitamin d analogues overall clinical effect of combination treatment lipid synthesis amps, eg ll-37 prevents skin barrier and water loss impairment caused by corticosteroids kc proliferation = attenuates epidermal thinning by corticosteroid-induced reduction of epidermal cells change in tissue modelling and structure: � hyaluronic acid � matrix metalloproteinases limits epidermal thinning from corticosteroid-induced loss of cellular volume collagen synthesis and turnover reduces dermal thinning caused by corticosteroid-induced decrease in matrix network glycosamine synthesis increases water-binding capacity of the skin, decreasing corticosteroidinduced dermal thinning elastic fibre synthesis attenuates reduced skin flexibility/ elasticity observed in topical steroidal monotherapy downward arrow indicates down-regulation, upward arrow indicates up-regulation, equal sign indicates no effect. the data presented here are based on non-inflamed skin. amp, antimicrobial peptide; kc, keratinocyte challenges of drug delivery in topical formulations � poor penetration of active ingredients into the skin can result in low, or lack of, clinical efficacy � the rate-limiting step for most topical treatments is the concentration of active ingredients dissolved in the vehicle � one potential method of enhancing the rate of skin penetration is to increase the concentration of active ingredients dissolved in the applied product beyond the normal solubility limit, ie create a supersaturated solution � a recent study with cal/bd aerosol foam demonstrated that a stable supersaturated environment was created and maintained for clinically relevant time periods (at least 26 hours in the laboratory setting)21 – this state was created after rapid evaporation of the propellants during application and may explain the observed increase in bioavailability of cal/bd aerosol foam versus cal/bd ointment21 an innovative drug delivery formulation results in improved efficacy � a number of studies have demonstrated the superior efficacy of cal/bd aerosol foam compared with traditional formulations such as ointments, gels, and lotions (table 2)15,22–24 � the increased efficacy of cal/bd aerosol foam is also associated with a similar safety profile, as demonstrated in a pooled safety analysis comparing fixed-dose combination cal/bd aerosol foam with bd foam, cal foam, cal/bd ointment, and vehicles (foam and ointment)25 table 2. summary of studies comparing cal/bd aerosol foam with cal/bd gel or ointment design duration n comparator(s) outcomes phase iia, exploratory, single centre, intra-individual comparison15 4 weeks 24 cal/bd foam vs cal/bd ointment vs bd foam vs foam vehicle (all n=24) tcs decrease: –6.00 vs –5.25 (cal/bd ointment; p=0.038) vs –4.96 (bd foam; p=0.005) phase ii, randomized, multicentre22 4 weeks 376 cal/bd foam (n=141) vs cal/bd ointment (n=135) vs foam (n=49) and ointment (n=51) vehicle treatment success rates: 54.6% vs 43.0% (cal/bd ointment; p=0.025) mpasi mean difference: –0.6 vs cal/bd ointment (p=0.005) phase iii, randomized, parallel group (pso able)23 12 weeks 463 cal/bd foam (n=185) vs cal/bd gel (n=188) vs foam (n=47) and gel (n=43) vehicles treatment success rates: 38% vs 22% (cal/bd gel; p<0.0001) mpasi mean difference: –0.6 vs cal/bd gel (p=0.028) phase iii, randomized, parallel group (pso-able, hrqol analysis)24 12 weeks 463 cal/bd foam (n=185) vs cal/bd gel (n=188) dlqi scores of 0/1: 60.5% vs 44.1% (cal/bd gel; p=0.003); eq-5d utility index: 0.09 vs 0.03 (cal/bd gel; p<0.001) all studies were investigator blinded. bd, betamethasone dipropionate; cal, calcipotriol; dlqi, dermatology life quality index; eq-5d, euroqol-5d-5l-pso; hrqol, health-related quality of life; mpasi, modified psoriasis area and severity index (excluding head, which was not measured); tcs, total clinical score (sum of erythema, scaling, and plaque thickness) innovation in topical therapy for psoriasis with corticosteroid and vitamin d analogue combination siegfried segaert,1 neil shear,2 andrea chiricozzi,3 diamant thaçi,4 jose manuel carrascosa,5 helen young,6 vincent descamps7 1dermatology department, university hospital leuven, leuven, belgium; 2division of dermatology, department of medicine, sunnybrook health sciences center and university of toronto, toronto, canada; 3dermatology department, university of pisa, pisa, italy; 4comprehensive center for inflammation medicine, university hospital schleswig-holstein, university of lübeck, lübeck, germany; 5department of dermatology, hospital universitari germans trias i pujol, universitat autònoma de barcelona, barcelona, spain; 6the dermatology research centre, division of musculoskeletal and dermatological sciences, the university of manchester, manchester academic health sciences centre, manchester, uk; 7department of dermatology, bichat-claude bernard hospital, paris 7 denis diderot university, paris, france p1922 poster presented at the 26th eadv congress, geneva, switzerland, 13–17 september 2017 � overall, fixed-dose combination of corticosteroids and vitamin d analogue has demonstrated superior efficacy over monotherapies in both preclinical and clinical studies, as well as in daily practice � the rationale for fixed-dose combination treatment is further supported by minimized adverse events usually associated with corticosteroid and vitamin d analogue monotherapy, such as skin atrophy and perilesional skin irritation, respectively � improved delivery of active ingredients via innovative formulations, eg aerosol foam, has shown improved clinical response and quality of life, while providing patients with more therapeutic options suited to their lifestyle � a randomized clinical trial with cal/bd aerosol foam has recently been initiated to examine the long-term management of plaque psoriasis (psolong; nct02899962) conclusions acknowledgements � this poster was sponsored by leo pharma � medical writing support was provided by mai kurihara, phd, from mudskipper business ltd, funded by leo pharma references 1. nestle fo et al. n engl j med 2009;361:496–509 2. hrehorow e et al. acta derm venereol 2012;92:67–72 3. kim j & krueger jg. dermatol clin 2015;33:13–23 4. laws pm & young hs. expert opin pharmacother 2010;11:1999–2009 5. menter a et al. j am acad dermatol 2009;60:643–59 6. bikle dd. j nutr 1995;125:1709s–14s 7. lange k et al. skin pharmacol appl skin physiol 2000;13:93–103 8. norris da. j am acad dermatol 2005;53:s17–25 9. segaert s & røpke m. j drugs dermatol 2013;12:e129–37 10. gottlieb a. psoriasis forum 2015;21:35–41 11. lovato p et al. j dermatol sci 2016;81:153–64 12. clark ra. j invest dermatol 2011;131:283–5 13. suarez-farinas m et al. j invest dermatol 2011; 131:391–400 14. lebwohl m et al. j clin aesthet dermatol 2016;9:34–41 15. queille-roussel c et al. clin drug investig 2015;35:239–45 16. scott lj et al. am j clin dermatol 2001;2:95–120 17. norsgaard h et al. arch dermatol res 2014;306:719–29 18. kragballe k et al. br j dermatol 2006;154:1155–60 19. schoepe s et al. exp dermatol 2006;15:406–20 20. jensen jd et al. arch dermatol 2011;147:95–8 21. lind m et al. dermatol ther (heidelb) 2016;6:413–25 22. koo j et al. j dermatolog treat 2016;27:120–7 23. paul c et al. j am acad dermatol 2016;74:ab260 (abst p3712) 24. paul c et al. j eur acad dermatol venereol 2017;31:119–26 25. menter a et al. skinmed 2017;15:119–24 fc17posterleosegaertinnovationtopicaltherapy.pdf ■ overall, 40.9% (312/763) of patients achieved complete disease clearance at least once during the study; this included 233 patients who entered the study with a physician global assessment (pga) score of ≥1 and 79 patients who entered with a pga of 04 ■ the median duration of remittive effect while off therapy for patients who entered the study with a pga of 0 was 115 days, and the mean total duration of remittive effect off therapy for patients who entered with, or achieved, a pga of 0 was 130 days4 ■ durability of response of up to 52 weeks was demonstrated with intermittent use of tapinarof cream 1% qd, indicating no observation of tachyphylaxis (defined as loss of response) while on therapy4 ■ tapinarof cream 1% qd was well tolerated with long-term use and had a safety profile consistent with previous studies2,5 results patient satisfaction questionnaire ■ 91.6% of eligible patients (n=763) completing psoaring 1 and 2 elected to enroll in psoaring 3 ■ patient satisfaction questionnaires were completed by 78.5% (599/763) of patients in psoaring 3 ■ patients consistently reported high satisfaction rates across all parameters, including patients’ satisfaction with tapinarof efficacy, formulation elegance, application ease, impact on daily life, and preference for tapinarof cream versus prior psoriasis therapies confidence and satisfaction with the efficacy of tapinarof cream ■ most patients either strongly agreed or agreed with all questions on confidence and satisfaction with the efficacy of tapinarof cream (figure 3) ■ 85.8% felt they could easily manage their psoriasis with tapinarof, and 83.6% were satisfied with how well tapinarof worked ■ in addition to the 40.9% of patients who achieved complete disease clearance and the observed remittive effect of ~4 months, 62.9% of patients either strongly agreed or agreed that tapinarof cleared their skin and kept psoriasis from coming back ■ 84.1% had confidence in tapinarof, and 84.0% would recommend tapinarof to other patients with psoriasis ■ 82.5% of patients would use tapinarof again or continue on tapinarof if it was available figure 3. confidence and satisfaction with the efficacy of tapinarof cream (n=599) ease of application and cosmetic elegance of tapinarof cream ■ patients were consistently very satisfied with the tapinarof cream formulation and elegance (figure 4) ■ 93.2% were satisfied with the time spent applying tapinarof, and 96.3% considered it easy to apply ■ in addition, most patients either strongly agreed or agreed that tapinarof was quickly absorbed (89.5%), felt good on their skin (79.9%), and was not greasy (89.0%) ■ 87.7% were very satisfied with the look and feel of tapinarof figure 4. ease of application and cosmetic elegance of tapinarof cream (n= 599) *n number for question is 598. †n number for question is 587. patient satisfaction with tapinarof cream 1% once daily for plaque psoriasis in a long-term extension trial jerry bagel,1 linda stein gold,2 james del rosso,3 neal bhatia,4 sandy johnson,5 paul yamauchi,6 angela y. moore,7 anna m. tallman8 1psoriasis treatment center of central new jersey, east windsor, nj, usa; 2henry ford health system, detroit, mi, usa; 3jdr dermatology research/thomas dermatology, las vegas, nv, usa and advanced dermatology & cutaneous surgery, maitland, fl, usa; 4therapeutics clinical research, san diego, ca, usa; 5johnson dermatology, fort smith, ar, usa; 6dermatology institute & skin care center, santa monica, ca, usa; 7arlington center for dermatology, arlington research center, arlington, tx, usa; 8dermavant sciences, inc., morrisville, nc, usa background ■ patient dissatisfaction with current therapies is an important barrier to optimal care of psoriasis (52% of psoriasis patients have reported dissatisfaction with their treatment1) and there is a need for efficacious, tolerable, easy-to-use topical therapies that can be used long term, including on sensitive skin areas ■ tapinarof 1% is a cosmetically elegant, once daily (qd) topical cream that does not contain added fragrance and is free of petrolatum, parabens, and gluten. the vehicle is specifically designed to reduce skin irritation and optimize the delivery of tapinarof to the target site ■ tapinarof cream 1% qd demonstrated significant efficacy and was well tolerated in two 12-week pivotal phase 3 trials of 1,025 adults with mild-to-severe plaque psoriasis, psoaring 1 (nct03956355) and psoaring 2 (nct03983980), and demonstrated favorable patient-reported local tolerability and investigator-assessed irritation scores including sensitive skin areas2,3 ■ psoaring 3 (nct04053387) was a 40-week, long-term, open-label extension trial to assess the efficacy, durability of response on therapy, duration of remittive effect off therapy, safety, and tolerability of tapinarof cream 1% qd ■ figure 1 displays photographs of the clinical response of a patient treated with tapinarof 1% qd who achieved primary and secondary efficacy, and patient-reported outcome (pro) endpoints figure 1. clinical response of a patient with plaque psoriasis who achieved primary and secondary efficacy, and pro endpoints pga and pasi are global efficacy assessments. example of one representative target lesion of one tapinarof-treated patient from psoaring 1 clinical trial. *dlqi was assessed at baseline, week 4 (no evaluation at week 8), and week 12. dlqi, dermatology life quality index; pasi, psoriasis area and severity index; pga, physician global assessment; pp-nrs, peak pruritus numeric rating scale. objective ■ given that patient dissatisfaction with current therapies has a significant impact on disease management, we assessed patient satisfaction using a patient satisfaction questionnaire; here we present the results from psoaring 3, a long-term, open-label extension trial of tapinarof cream 1% qd methods study design ■ patients completing psoaring 1 and psoaring 2 were eligible to enroll in psoaring 3 for up to 40 weeks of open-label treatment with tapinarof cream 1% qd, followed by 4 weeks of follow-up (figure 2) ■ the patient satisfaction questionnaire was designed to assess patients’ satisfaction with tapinarof efficacy, formulation elegance, application ease, impact on daily life, and preference for tapinarof cream versus prior psoriasis therapies – the questionnaire included a series of 18 questions with responses on a scale of strongly agree, agree, neutral, disagree, or strongly disagree ■ patient satisfaction questionnaire responses were assessed at week 40 (or early termination visit) and summarized overall figure 2. psoaring 3 study design four patients (3 tapinarof, 1 vehicle) did not have a baseline pga and are listed as missing. pga, physician global assessment; qd, once daily. previously reported efficacy outcomes from psoaring 3 ■ tapinarof cream 1% qd demonstrated continued and substantial improvement in efficacy with long-term use, beyond the improvements already observed in the 12-week pivotal trials, psoaring 1 and 22,4 • pga=4 • pasi=18.4 • dlqi=16 • pp-nrs=6 • pga=2 • pasi=0.9 • dlqi=4* • pp-nrs=0 • pga=1 • pasi=0.6 • dlqi=1 • pp-nrs=0 baseline week 8 week 12 off treatment off treatment pga=0 (n=79) pga=0 stop treatment pga≥2 re-start treatment pga≥1 (n=680) tapinarof 1% qd pivotal (n=508) tapinarof 1% qd vehicle qd pivotal (n=255) long-term open-label extension (40 weeks) follow-up (4 weeks) double-blind treatment (12 weeks) 85.8 4.5 2.5 7.2 easily manage psoriasis with tapinarof 83.6 6.3 2.3 7.7 satisfied with how well tapinarof worked 84.1 5.2 1.5 9.2 have confidence in tapinarof 62.9 12.5 5.2 19.4 tapinarof cleared skin and prevented psoriasis from coming back 84.0 4.2 2.3 9.5 if available would recommend tapinarof to others 82.5 6.2 3.2 8.2 if available would use tapinarof again or continue on it p ro p o rt io n o f p a ti e n ts , % 30 40 70 80 90 100 60 50 20 10 0 strongly agree + agree neutral disagree strongly disagree 96.3 0.5 0.5 2.7 93.2 2.0 0.7 4.2 89.0 2.5 0.5 8.0 89.5 2.0 0.3 8.2 79.9 2.2 0.8 17.1 87.7 1.7 0.3 10.2 p ro p o rt io n o f p a ti e n ts , % 30 40 70 80 90 100 60 50 20 10 0 tapinarof was easy to apply time spent applying was acceptable and did not impact everyday life tapinarof was not greasy tapinarof quickly absorbs tapinarof feels good on skin* satisfied with look and feel of tapinarof† strongly agree + agree neutral disagree strongly disagree strongly agree + agree neutral disagree strongly disagree 81.7 4.2 1.9 12.1 65.3 2.9 0.6 31.2 81.1 4.2 1.5 13.1 55.3 12.6 7.0 25.1 63.8 10.1 4.5 21.6 67.8 11.1 4.5 16.6 p ro p o rt io n o f p a ti e n ts , % a. versus prior topical therapies (n=519) b. versus prior systemic therapies (n=199) 30 40 70 80 90 100 60 50 20 10 0 tapinarof was more effective than topical drugs i have used in the past tapinarof was easier to use than topical drugs i have used in the past i prefer tapinarof to topical drugs i have used in the past tapinarof was more effective than systemic drugs i have used in the past tapinarof was easier to use than systemic drugs i have used in the past i prefer tapinarof to systemic drugs i have used in the past preference for tapinarof cream versus prior topical psoriasis therapies ■ for patients who reported having used other topical drugs to treat psoriasis in the past, 81.7% considered tapinarof to be more effective than prior therapies, and 65.3% considered tapinarof easier to use (figure 5a) ■ 81.1% of patients preferred tapinarof to other topical drugs used to treat their psoriasis in the past preference for tapinarof cream versus prior systemic psoriasis therapies ■ for patients who reported having used systemic drugs to treat psoriasis in the past, 55.3% considered tapinarof to be more effective than prior therapies, and 63.8% considered tapinarof to be easier to use (figure 5b) ■ most patients (67.8%) also preferred tapinarof to systemic drugs used to treat their psoriasis in the past figure 5. patient preference for tapinarof cream versus prior topical and systemic therapies conclusion ■ patient satisfaction data from psoaring 3 demonstrate a consistent and highly positive perception of tapinarof cream 1% qd across all patient relevant parameters, including satisfaction with tapinarof efficacy, formulation elegance, application ease, impact on daily life, and preference for tapinarof cream versus prior psoriasis therapies references 1. armstrong aw, et al. jama dermatol. 2013;149:1180–1185; 2. lebwohl m, et al. n engl j med. 2021;385:2219–2229; 3. bissonnette r, et al. poster presented at: international federation of psoriasis associations; june 30–july 3, 2021; virtual; 4. strober b, et al. oral presented at: european academy of dermatology and venereology; september 30, 2021; virtual; 5. robbins k, et al. j am acad dermatol. 2019;80:714–721. acknowledgments trials were funded by dermavant sciences, inc. and the authors thank the investigators, patients and their families, and colleagues involved in their conduct. j.b. has received research funds payable to psoriasis treatment center and/or speaking/consultant fees from abbvie, amgen, arcutis biotherapeutics, boehringer ingelheim, bristol myers squibb, celgene, corrona llc, dermavant sciences, ltd, dermira/ucb, eli lilly, glenmark pharmaceuticals ltd, janssen biotech, kadmon corporation, leo pharma, lycera corp, menlo therapeutics, novartis, pfizer, regeneron, sun pharma, taro pharmaceutical industries ltd, ucb, and valeant pharmaceuticals. l.s.g. has served as a consultant, and/or has received payment for the development of educational presentations, and/or has received grants from arcutis, amgen, bristol myers squibb, dermavant sciences, inc., eli lilly, leo pharma, ortho dermatologic, and ucb biopharma. j.d.r. is a consultant and research investigator for dermavant sciences, inc. n.b. is a consultant with honorarium and an investigator for dermavant sciences, inc. sj is an advisor and/or speaker and/or editor and/or involved in clinical trials for abbvie, aclaris, afmc, allergan, candela syneron, cassiopea, celgene, amgen, chemocentryx, dermavant sciences, inc., dermira, foamix, gage, galderma, gsk, journal of arkansas medical society, leo, eli lilly, national psoriasis foundation, nielsen, novartis, practical dermatology, regeneron, sanofi genzyme, skin medical, target therapeutics, and the university of pennsylvania. p.y. has served as an investigator and/or speaker and/or consultant for abbvie, amgen, arcutis, bms, dermavant, epi health, incyte, janssen, lilly, leo, novartis, pfizer, sun pharma, and ucb. a.y.m. has served as an investigator for dermavant sciences, inc. a.m.t. is an employee of dermavant sciences inc., with stock options. editorial and medical writing support under the guidance of the authors was provided by apothecom, uk, and was funded by dermavant sciences, inc. in accordance with good publication practice (gpp3) guidelines (ann intern med. 2015;163:461–464). contact dr bagel at dreamacres1@aol.com with questions or comments. skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 923 brief article syphilis in hiv positive individuals and the importance of a skin exam: a case report aditi chokshi1, amaury diaz, md2 1nova southeastern university college of osteopathic medicine, fort lauderdale, fl 2lee memorial hospital department of infectious disease, fort meyers, fl despite advances in screening, diagnosis, and treatment, the prevalence of syphilis has been at a near historic high during the past decade.1 early recognition of characteristic symptoms and treatment can curtail a larger outbreak from occurring. typical primary syphilis is characterized by a single painless lesion in the anal or genital region that ulcerates to form a “chancre”. progression to secondary syphilis occurs within two to eight weeks with appearance of a maculopapular rash that can involve the palms and soles. if progression to tertiary syphilis occurs, patients can develop severe complications such as gummas, aortitis, tabes dorsalis, and argyll robertson pupils.2 syphilis in hivinfected patients often has an atypical presentation with higher rates of asymptomatic primary syphilis and accelerated disease progression. consequently, syphilis amongst hiv patients often goes undiagnosed until it has progressed to the secondary stage of disease.3secondary infection in hiv patients is more aggressive with increased rates of neurocognitive effects and ophthalmic involvement.4 a 68-year-old hiv-positive male presented with perianal painless erythematous lesions for a 6-week duration. (figure 1). he denied a history of stds or chronic diarrhea. previous treatment with antibiotics showed no improvement. the patient went to his primary care physician twice before receiving a referral to a gastroenterologist to be abstract among hiv-positive patients, co-infection with syphilis is estimated to be as high as 20%. the diagnosis of syphilis is often missed due to its asymptomatic nature during its primary stages. a 68-year-old hiv-positive male presented with perianal lesions to his primary care physician twice. he was then referred to two different specialists before a proper physical exam was conducted after which he was diagnosed with otosyphilis and neurosyphilis. physicians should have a higher index of clinical suspicion for syphilis in hiv-positive patients to allow for prompt diagnosis given the propensity of these patients to develop more severe neurological and ophthalmologic manifestations. this case highlights the importance of a thorough skin exam by a primary care physician when examining patients to allow for an earlier and accurate diagnosis and thus avoiding unnecessary referrals to specialists. introduction case report skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 924 evaluated with flexible sigmoidoscopy and biopsy. pathologic evaluation showed significant acute/chronic inflammation and no malignancy. the patient developed further symptoms of tinnitus and headache and was treated with azithromycin with no improvement. the patient was then referred to an infectious disease specialist where a generalized morbilliform macular rash was observed. (figures 2 and 3). an rpr yielded a positive result, and the patient was diagnosed with otosyphilis and neurosyphilis. the patient was admitted to the hospital and treated with 4 million units of iv penicillin g q4 for 14 days. figure 1. clinical presentation of painless erythematous perianal lesions. syphilis is known as “the great imitator” due to its ability to mimic a myriad of other diseases. the characteristic rash is non pruritic and often has a superficial scale on the lesions. this can result in misdiagnosis of psoriasis in some patients. other differential diagnoses include pityriasis rosea, drug eruptions, lichen planus and acute febrile exanthems. recognition of the unique palm and sole lesions and morbilliform rash seen in syphilis patients is crucial for early detection and treatment.1 however, the diagnosis is often not made until patients have already developed more severe complications. the recognition of the classic maculopapular morbilliform rash associated with syphilis is often not considered by physicians who do not have specialized training in evaluation of rashes.5 figure 2. characteristic maculopapular secondary syphilis rash on trunk. figure 3. secondary syphilitic lesions on flank. although serologic tests are considered the mainstay of syphilis diagnosis,6 hiv-positive patients could experience serological failure discussion skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 925 such as the prozone reaction compared with hiv-negative patients.7 therefore, clinicians must rely on a thorough history, physical exam, and high index of clinical suspicion to facilitate a diagnosis.8 several cases of misdiagnosed syphilis in hiv patients have been previously reported which further emphasizes the importance of early diagnosis.9-11 the patient discussed in this case visited his primary care doctor with concerns regarding his persistent perianal lesions. the primary care physician prescribed prophylactic antibiotics and had him return for a follow-up visit. the primary care physician focused only on the lesions around the anal region instead of performing a thorough exam. given the high prevalence of coinfection of hiv and syphilis and risk of more aggressive diseases, physicians should take extra precautionary measures to ensure diagnoses are not missed. the patient was subjected to an invasive procedure that yielded no significant result and referred again to another specialist. ultimately, the infectious disease physician noted the classic maculopapular rash throughout the trunk, arms, and back that resulted in a diagnosis. this case emphasizes the importance of a proper skin exam in each patient. if a proper skin examination was performed, the patient may not have progressed to otosyphilis and neurosyphilis and required hospitalizations along with medical bills from four different specialists. by increasing recognition of the characteristic skin rash in patients, earlier detection and treatment can be started to avoid transmission to partners and further increasing the surge in syphilis cases in the united states. this case emphasizes the importance of training on recognizing characteristic rashes and performing a thorough full-body skin exam during each patient encounter. untreated syphilis can result in significant patient mortality and morbidity. by increasing the awareness of syphilis prevalence and atypical presentations amongst hiv-positive patients, physicians can prevent further increase in syphilis cases and transmission from patients to their partners. conflict of interest disclosures: none funding: none corresponding author: aditi chokshi nova southeastern college of osteopathic medicine fort lauderdale, fl email: chokshi.aditi00@gmail.com references: 1. clement, m. e., & hicks, c. b. (2016). syphilis on the rise: what went wrong?. jama, 315(21), 2281-2283. 2. dylewski, j., & duong, m. (2007). the rash of secondary syphilis. cmaj, 176(1), 33-35. 3. german, m. n., matkowskyj, k. a., hoffman, r. j., & agarwal, p. d. (2018). a case of syphilitic hepatitis in an hiv-infected patient. human pathology, 79, 184-187. 4. hernandez, i., johnson, a., reina-ortiz, m., rosas, c., sharma, v., teran, s., ... & izurieta, r. (2017). syphilis and hiv/syphilis co-infection among men who have sex with men (msm) in ecuador. american journal of men's health, 11(4), 823-833. 5. çakmak, s. k., tamer, e., karadağ, a. s., & waugh, m. (2019). syphilis: a great imitator. clinics in dermatology, 37(3), 182-191. 6. schmidt, r., carson, p. j., & jansen, r. j. (2019). resurgence of syphilis in the united states: an assessment of contributing factors. infectious diseases: research and treatment, 12, 1178633719883282. 7. tong, m. l., lin, l. r., liu, g. l., zhang, h. l., zeng, y. l., zheng, w. h., … & yang, t. c. (2013). factors associated with serological cure and the serofast state of hiv-negative patients conclusion skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 926 with primary, secondary, latent and tertiary syphilis. plos one, 8(7), e70102 8. lynn, w.a., & lightman, s. (2004). syphilis and hiv: a dangerous combination. the lancet infectious diseases, 4(7), 456-466 9. seña, a. c., zhang, x. h., li, t., zheng, h. p., yang, b., yang, l. g., ... & tucker, j. d. (2015). a systematic review of syphilis serological treatment outcomes in hiv-infected and hivuninfected persons: rethinking the significance of serological non-responsiveness and the serofast state after therapy. bmc infectious diseases, 15(1), 1-15. 10. chen, b., peng, x., xie, t., jin, c., liu, f., & wu, n. (2017). the tradition algorithm approach underestimates the prevalence of serodiagnosis of syphilis in hiv-infected individuals. plos neglected tropical diseases, 11(7), e0005758. 11. forrestel, a. k., kovarik, c. l., & katz, k. a. (2020). sexually acquired syphilis: laboratory diagnosis, management, and prevention. journal of the american academy of dermatology, 82(1), 17-28. skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 511 brief article comorbidities, healthcare utilization, and costs associated with alopecia totalis and alopecia universalis in the united states arash mostaghimi, md, mph, mpa1, aster meche, mph2, markqayne ray, pharmd, mba3, kavita gandhi, ms3, david gruben, phd4, vanja sikirica, pharmd, mph3 1 brigham and women’s hospital, harvard medical school, boston, ma 2 pfizer inc., new york, ny 3 pfizer inc., collegeville, pa 4 pfizer inc., groton, ct alopecia areata (aa) is an autoimmune disorder with a lifetime incidence of 2%.1 up to 7% of patients with aa may experience more progressive hair loss, either affecting all scalp hair (alopecia totalis; at) or the entire scalp, face, and body surface area (alopecia universalis; au). patients with at or au abstract background: alopecia areata (aa) is an autoimmune disease characterized by nonscarring hair loss. extensive forms of aa include alopecia totalis (at; complete scalp hair loss) or alopecia universalis (au; complete scalp, face, and body hair loss). limited information exists about the cost and healthcare burden of at and au. methods: using a large us administrative healthcare claims database, two mutually exclusive patient cohorts were identified: aa cohort: ≥1 diagnosis of aa; at/au cohort: ≥1 diagnosis of at/au between january 1 and december 31, 2017. baseline characteristics measured at first aa diagnosis (index date) and all-cause healthcare utilization and costs identified in the 1-year post-index period were compared between at/au and non-at/au aa cohorts. results: 14,340 patients with aa were identified, including 1,224 patients with at or au. compared with patients with non-at/au aa (n=13,116), patients with at/au were older (mean age 43.1 vs 40.6 years, p<0.0001) and more were female (68.1% vs 62.9%, p<0.0001). more patients with at/au had baseline comorbidities (atopic disease [28.3% vs 24.1%], anemia [10.4% vs 7.4%], autoimmune disorders [9.6% vs 5.5%]; p≤0.001 for all). post-index patients with at/au had higher per person per policy year healthcare resource utilization and costs (p≤0.001) and total adjusted annual mean costs (p<0.05). over 50% more patients with at/au received immunosuppressive agents than patients with non-at/au aa. conclusion: patients with at/au had higher rates of comorbidities and greater healthcare resource utilization medical costs than patients with non-at/au aa, suggesting that improved insight into the patterns of specific comorbid conditions is needed. introduction skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 512 seldom experience spontaneous recovery.2-4 treatment efficacy is variable and limited in this subset of aa patients, with cases often recalcitrant to treatment.5 although comorbidities such as atopic dermatitis, anxiety, and mood disorders are associated with aa,6 limited information exists about the financial and healthcare resource burden of aa including at/au. in our prior study of a large retrospective cohort of us administrative healthcare claims data (iqvia pharmetrics® plus), patients with aa including at/au (n=14,340) had significantly higher mean per-patient-peryear (pppy) healthcare resource utilization (hcru) and total all-cause medical costs compared with matched non-aa controls ($9,154 vs $5,787; p<0.0001).7 the high rate of comorbidities (other autoimmune disorders, cardiovascular disease, and malignancy) contributed to the increased costs in aa. increased costs due to inpatient stay, emergency department (ed) and ambulatory visits, and prescription spending were also observed. in this study, using the same retrospective cohort of us administrative healthcare claims data (iqvia pharmetrics® plus8) of patients with aa, we further evaluated the baseline characteristics and the 1-year all-cause hcru and medical costs in patients with at/au only in comparison with patients with non-at/au aa. briefly, data for the study included all patients with continuous pharmacy and medical enrollment between january 1 and december 31, 2017. patients with aa (at/au and non-at/au) were required to have continuous pharmacy and medical enrollment in the database for 365 days before the first encountered aa diagnosis (index date) known as baseline period and for 365 days after the index date (evaluation period). two mutually exclusive criteria for patient cohorts were identified: aa cohort: ≥1 diagnosis of aa (icd-10 = l63.*); at/au cohort: ≥1 diagnosis of at/au (in any icd-10 code position [l63.0 and l63.1])9 between january 1 and december 31, 2017. all-cause healthcare costs and utilization measures were identified in the 365-day post-index period while variables such as age, sex, region, and payer type were measured at index. quan-charlson’s comorbidity index10 was measured during the 365-day baseline period. all demographics, clinical characteristics, comorbidities, hcru, medical, and pharmacy costs were analyzed descriptively and mean, median, and standard deviation reported on unadjusted observed costs. costs were adjusted to 2018 us dollars using the medical care component of the consumer price index.11 full details of study design and methods have been reported previously.7 a subset of 1,224 patients with at or au were identified from the aa population, which represented 9% of the total aa cohort (n=14,340). compared with patients with non-at/au aa (n=13,116), patients with at/au were slightly older (mean age 43.1 years vs 40.6 years, p<0.0001) and more were female (68.1% vs 62.9%, p<0.0001) (table 1). approximately one-third of the at/au and non-at/au aa claims were initiated by a dermatologist. the proportion of patients with comorbidities at baseline was higher in the at/au cohort, for atopic disease (28.3% vs 24.1%), anemia (10.4% vs 7.4%), and autoimmune disorders (9.6% vs 5.5%; p≤0.001 for all). pre-index, all-cause total costs were also higher in patients with at/au methods results skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 513 table 1. baseline patient demographics, clinical characteristics, and costs clinical characteristics are within 365 days pre-index. at, alopecia totalis; au, alopecia universalis; cvd, cardiovascular disease; iqr, interquartile range; qcci, quancharlson comorbidity index; sd, standard deviation variable at or au n = 1,224 non-at/au n = 13,116 p value age on index date, y <0.0001 mean (sd) 43.14 (15.44) 40.58 (14.62) median (iqr) 45 (32-55) 41 (30-52) age grouping categories, n (%) <0.0001 12-17 y 91 (7.43) 957 (7.30) 18-44 y 504 (41.18) 6,652 (50.72) 45-64 y 568 (46.41) 5,123 (39.06) ≥65 y 61 (4.98) 384 (2.93) sex, n (%) 0.0003 female 834 (68.14) 8,254 (62.93) male 390 (31.86) 4,862 (37.07) region, n (%) <0.0001 midwest 271 (22.14) 3,530 (26.91) northeast 334 (27.29) 3,013 (22.97) south 442 (36.11) 4,986 (38.01) west 177 (14.46) 1,587 (12.10) payor, n (%) 0.86 commercial 1,196 (97.71) 12,844 (97.93) medicaid 18 (1.47) 181 (1.38) medicare 10 (0.82) 91 (0.69) baseline pre-qcci score mean (sd) 0.44 (1.04) 0.30 (0.81) <0.0001 median 0 0 qcci categories, n (%) <0.0001 0 comorbidities 926 (75.65) 10,752 (81.98) 1-2 comorbidities 250 (20.42) 2,065 (15.74) 3-4 comorbidities 29 (2.37) 218 (1.66) ≥5 comorbidities 19 (1.55) 81 (0.62) cvd at baseline, n (%) 190 (15.52) 1,763 (13.44) 0.045 autoimmune disorder at baseline, n (%) 118 (9.64) 718 (5.47) <0.0001 atopic disease at baseline, n (%) 346 (28.27) 3,155 (24.05) 0.001 anemia at baseline, n (%) 127 (10.38) 969 (7.39) 0.0002 pre-index dermatologist visit, n (%) 489 (39.95) 5,158 (39.33) 0.69 pre-index count of dermatologist visits mean (sd) 1.24 (2.41) 1.17 (2.48) 0.36 median 0 0 pre-index all-cause total cost mean (sd) $10,060 ($17,701) 7,250 (14,272) <0.0001 median 3,421 2,473 skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 514 table 2. healthcare resource utilization and costs within 365 days post-index adjusted for 12m pre-index total cost, 12m pre-index qcci comorbidity score, 12m pre-index presence of cvd, autoimmune disorder, atopic disease, anemia, gender, age region. 1includes durable medical equipment, home healthcare, and additional miscellaneous categories at, alopecia totalis; au, alopecia universalis; ci, confidence interval; cvd cardiovascular disease; qcci, quancharlson comorbidity index; sd, standard deviation variable at or au n = 1,224 non-at/au n = 13,116 p value difference ($) % of the total difference inpatient visits, mean (sd) number of visits 0.06 (0.30) 0.05 (0.28) 0.25 costs, $ 1,291 (12,807) 1,162 (9,268) 0.001 128 3.53 emergency department visits, mean (sd) number of visits 0.21 (0.61) 0.23 (0.66) 0.45 costs, $ 455 (1,866) 495 (2,084) 0.0002 –41 –1.13 ambulatory visits, mean (sd) number of visits 14.8 (13.9) 13.6 (13.1) 0.003 costs, $ 4,735 (11,141) 3,538 (7,202) 0.007 1,197 32.98 other visits,1 mean (sd) number of visits costs, $ 1.50 (6.02) 812 (4,430) 0.97 (4.13) 538 (2,783) 0.002 <0.0001 274 7.55 pharmacy prescriptions filled, mean (sd) number of prescriptions 20.22 (23.0) 16.56 (21.47) <0.0001 costs, $ 5,180 (18,440) 3,111 (15,439) 0.0001 2,070 57.04 total costs, $, mean (sd) 12,473 (30,422) 8,844 (23,246) <0.0001 3,629 100 adjusted costs, $, mean (95% ci) 8,659 (7,452– 10,061) 7,555 (6,809– 8,383) 0.03 1,104 – skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 515 table 3. sensitivity analysis: healthcare resource utilization and costs excluding patients with a cancer diagnosis within 365 days preand post-index at, alopecia totalis; au, alopecia universalis; sd, standard deviation variable at/au n = 1,104 non-at/au n = 12,340 p value inpatient visit, mean (sd) no. of visits 0.06 (0.30) 0.04 (0.26) 0.09 costs, $ 1,292 (13,317) 1,017 (8,828) 0.50 ed visit, mean (sd) no. of visits 0.21 (0.61) 0.23 (0.65) 0.41 costs, $ 398 (1,473) 485 (2,067) 0.06 ambulatory visit, mean (sd) no. of visits 13.75 (12.66) 13.05 (12.74) 0.08 costs, $ 3,631 (6,762) 3,110 (5,196) 0.01 other visit, mean (sd) no. of visits 1.37 (5.90) 0.90 (3.65) 0.01 costs, $ 676 (4,275) 500 (2,732) 0.18 prescriptions filled, mean (sd) no. of prescriptions filled 19.20 (22.12) 15.93 (20.79) <0.0001 costs, $ 4,396 (15,073) 2,779 (14,114) 0.0006 total costs, $, mean (sd) 10,393 (24,405) 7,891 (20,627) 0.001 skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 516 vs patients with non-at/au aa (p<0.0001) (table 1). post-index patients with at/au had higher per person per policy year (pppy) hcru and costs vs patients with non-at/au aa (p≤0.001), with a greater number of inpatient, ambulatory, and other types of outpatient visits (e.g., durable medical equipment, home healthcare, and additional miscellaneous categories) (table 2). the mean number of prescriptions filled accounted for over 50% of the total cost difference between the two groups, with incremental costs of us$2,070 pppy. the overall total cost in the at/au cohort was us$3,629 greater than patients with non-at/au aa. there were greater total adjusted annual mean costs for at/au vs non-at/au aa (p<0.05). during the study period, over 50% more patients with at/au used immunosuppressive agents, mainly selective immunosuppressants (34%), than patients with non-at/au aa. given concern for possible misdiagnosis of patients with chemotherapy-related alopecia, a sensitivity analysis was performed excluding patients with a cancer diagnosis within 365 days pre and post-index which demonstrated maintained higher costs for the at/au cohort (table 3). this retrospective healthcare claims analysis used stratification of aa patients to identify a subset of at/au patients to compare hcru and healthcare costs in patients diagnosed with at/au with non-at/au aa. the study shows that patients with at/au have more comorbidities at baseline, including higher incidence of autoimmune disorders, atopic disease, and anemia. further, upon evaluation of total healthcare costs that include any comorbidity-related costs, we note patients with at/au incur more hcru and costs. these differences are attributable to a higher number of healthcare visits and higher pharmacy spending in at/au compared with non-at/au aa. our study findings of higher comorbidities in patients with at/au than in patients with nonat/au aa suggest that improved insight into the patterns of specific comorbid conditions, especially those that are not considered or known to be associated with aa (e.g., cardiovascular disease), is required. future studies should evaluate long-term outcomes including any consideration of newer treatments in this patient population. acknowledgments: this study was funded by pfizer. medical writing support was provided by sharmy blows, phd, of engage scientific solutions and was funded by pfizer inc. conflict of interest disclosures: amo reports consulting fees from pfizer inc., hims, and 3derm and equity from lucid and hims. ame and dg are employees of and may hold stock and/or stock options from pfizer. mr, kg, and vs were employees of pfizer inc. when this study was conducted and may hold stock and/or stock options from pfizer inc. funding: this study was funded by pfizer inc. corresponding author: arash mostaghimi, md, mph, mpa department of dermatology brigham and women’s hospital 221 longwood ave boston, ma 02115 email: amostaghimi@bwh.harvard.edu references: 1. villasante fricke ac, miteva m. epidemiology and burden of alopecia areata: a systematic review. clin cosmet investig dermatol 2015;8:397-403. 2. alkhalifah a, alsantali a, wang e, mcelwee kj, shapiro j. alopecia areata update: part ii. treatment. j am acad dermatol 2010;62(2):191-202. 3. alkhalifah a, alsantali a, wang e, mcelwee kj, shapiro j. alopecia areata update: part i. clinical picture, histopathology, and discussion skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 517 pathogenesis. j am acad dermatol 2010;62(2):177-88. 4. macdonald hull sp, wood ml, hutchinson pe, sladden m, messenger ag, british association of dermatologists. guidelines for the management of alopecia areata. br j dermatol 2003;149(4):692-9 5. lai vwy, chen g, gin d, sinclair r. systemic treatments for alopecia areata: a systematic review. australas j dermatol 2019;60(1):e1e13. 6. lee s, lee h, lee ch, lee ws. comorbidities in alopecia areata: a systematic review and meta-analysis. j am acad dermatol 2019;80(2):466-77 e16. 7. mostaghimi a, xenakis j, meche a, smith tw, gruben d, sikirica v. economic burden and healthcare resource use of alopecia areata in an insured population in the usa. dermatol ther (heidelb). 2022 apr;12(4):1027-1040. 8. iqvia. us claims iqvia pharmetrics plus, https://www.iqvia.com/library/factsheets/iqvia-pharmetrics-plus; [accessed january 11, 2021]. 9. lavian j, li sj, lee ey, bordone la, polubriaginof fcg, christiano am, et al. validation of case identification for alopecia areata using international classification of diseases coding. int j trichology 2020;12(5):234-7. 10. quan h, li b, couris cm, fushimi k, graham p, hider p, et al. updating and validating the charlson comorbidity index and score for risk adjustment in hospital discharge abstracts using data from 6 countries. am j epidemiol 2011;173(6):676-82. 11. united states department of labor. consumer price indexes—all urban consumers [internet]. washington, dc: united states department of labor. available at: https://www.bls.gov/cpi/home.htm. powerpoint presentation empedobacter brevis, as a part of the flavobacteriaceae family, is a non-motile, strictly aerobic, gram negative, yellow colony-forming bacterium that typically resides in soil, plants, water sources, and hospital environments.1,2 the first reported case of a human infection was in 2002 when 11 out of 12 patients were diagnosed with endophthalmitis from an e. brevis infection post cataract surgery.3 more cases of e. brevis infections have since been reported ranging from meningitis to cellulitis.3,4,6 treatment can be complicated by the bacteria’s beta lactamase gene, which results in resistance to extended cephalosporins and carbapenems.5 there have been a few dermatologic manifestations of e. brevis infections reported in the literature that warrant further evaluation.6,7 we present a case of an e. brevis infection in a 61-year-old male who presented with a persistent right mid-thigh lesion. introduction a rare case of empedobacter brevis cutaneous infection treated successfully with oral sarecycline susuana adjei, md1; austinn c. miller, md 1; laurie a. temiz, ba2 ; stephen k. tyring, md, phd, mba 1,3 1center for clinical studies webster, tx; 2meharry medical college, nashville, tn; 3ut houston department of dermatology, houston tx discussion thought to be an environmental pathogen, increasing cases of human e. brevis infections are now being reported as portrayed in table 1. there have been cases ranging from neonates to the elderly, namely those who are immunocompromised. exposure of e. brevis can be from hospital facilities to soils, water sources, and plants-as also depicted in some of the reported cases. while human e. brevis infections increase, its dermatologic manifestations are also emerging. e. brevis is not found on normal skin flora, so skin infections tend to stem from environmental exposure from breaks in the skin such as the knee laceration with cellulitis and foot lesion with anaphylactoid purpura and blisters. treatment of infections due to e. brevis is by antibiotics that have activity against gram-negatives. however, this is only complicated by resistance to certain beta-lactams due to e. brevis’ beta-lactamase gene, conferring resistance to extended cephalosporins and carbapenems, as demonstrated by the sensitivities from our patient. patient information case details sensitivity results/treatment 65 yo female with pmh of copd, brown sequard syndrome right knee cellulitis & bacteremia due to e. brevis 6 weeks post right knee replacement & subsequent fall with knee laceration sensitive to most antibiotics treated with levaquin for 10 days 83 yo female presented with anaphylactoid purpura, erythema, blisters, and erosion of the right foot. e. brevis was cultured from the lesion. biopsy showed leukocytoclastic vasculitis. sensitive: minocycline hcl treated with minocycline hcl table 1. reported cases of skin infections due to e. brevis case presentation a 61-year-old male with a past medical history of hypertension, actinic keratoses, history of valve replacement (chronically on warfarin) and prior knee replacement surgery presented with a lesion that persisted for 6 weeks after doing yard work. he reported using hydrogen peroxide and antibiotic bandages with no improvement. physical exam a non-painful right mid-thigh red, crusted linear erosion with honey-yellow crusting. culture empedobacter brevis was identified by dna sequencing. resistant to meropenem and tobramycin treatment patient was initially treated with mupirocin with no improvement. 15-day course of 150mg once-daily. sarecycline was added after the results returned and the lesion healed well over the upcoming weeks. figure 1. lesion at initial visit figure 3. one-month posttreatment figure 2. lesion after a week of seracycline 1. vandamme p, bernardet jf, segers p, kersters k, holmes b. new perspectives in the classification of the flavobacteria: description of chryseobacterium gen. nov., bergeyella gen. nov., and empedobacter nom. rev. international journal of systematic and evolutionary microbiology. 1994 oct 1;44(4):827-31 2. jooste pj, hugo cj. the taxonomy, ecology and cultivation of bacterial genera belonging to the family flavobacteriaceae. international journal of food microbiology. 1999 dec 15;53(2-3):81-94. 3. janknecht p, schneider cm, ness t. outbreak of empedobacter brevis endophthalmitis after cataract extraction. graefes arch clin exp ophthalmol. 2002 apr;240(4):291-5. doi: 10.1007/s00417-002-0435-5. epub 2002 mar 12. pmid: 11981643 4. sharma d, patel a, soni p, sharma p, gupta b. empedobacter brevis meningitis in a neonate: a very rare case of neonatal meningitis and literature review. case rep pediatr. 2016;2016:7609602. doi:10.1155/2016/7609602 5. bellais s, girlich d, karim a, nordmann p. ebr-1, a novel ambler subclass b1 beta-lactamase from empedobacter brevis. antimicrob agents chemother. 2002 oct;46(10):3223-7. doi: 10.1128/aac.46.10.3223-3227.2002. pmid: 12234848; pmcid: pmc128804 6. raman s, shaaban h, sensakovic jw, perez g. an interesting case of empedobacter brevis bacteremia after right knee cellulitis. j glob infect dis. 2012;4(2):136-137. doi:10.4103/0974-777x.96783 7. nishio e. [a case of anaphylactoid purpura suggested to empedobacter (flavobacterium) brevis infection concerned]. arerugi. 2010 may;59(5):558-61. japanese. pmid: 20502105.] acknowledgements we would like to thank the patient for providing permission to report his case. references conflict of interest dr. stephen k. tyring is a principal investigator for a clinical trial for one of almirall’s trials. ♦ ixekizumab is a high-affinity monoclonal antibody that selectively targets interleukin-17a1 ♦ ixekizumab was superior to placebo in achieving clinical responses and inhibiting progression of structural joint damage in patients with psoriatic arthritis treated for 24 weeks2 • the efficacy of ixekizumab in providing persistence of clinical responses through 52 weeks of treatment has been shown in spirit-p13,4 radiographic progression of structural joint damage in patients with active psoriatic arthritis treated with ixekizumab over 52 weeks désirée van der heijde,1 masato okada,2 chin lee,3 catherine l. shuler,3 suchitrita rathmann,3 chen-yen lin,3 philip j. mease4 1leiden university medical centre, leiden, the netherlands; 2st. luke’s international hospital, tokyo, japan; 3eli lilly and company, indianapolis, usa; 4swedish medical center and university of washington, seattle, usa background 2017 fall clinical dermatology conference (fall cdc 2017); las vegas, nevada; october 12-15, 2017; previously presented at eular 2017 sponsored by eli lilly and company and/or one of its subsidiaries disclosures ♦ d. van der heijde is a consultant for: abbvie, amgen, astellas, astrazeneca, bristol-myers squibb, boehringer ingelheim, celgene, daiichi-sankyo, eli lilly and company, galapagos, gilead, janssen, merck, novartis, pfizer, regeneron, roche, sanofi, ucb, and director of imaging rheumatology bv; m. okada is a consultant for and has received grant/research support from: eli lilly and company, is on the speaker’s bureau of: santen pharmaceutical, mitsubishi tanabe pharma, pfizer, abbott japan; c. lee; c. l. shuler; s. rathmann; and c-y. lin are current employees and shareholders of: eli lilly and company; p. j. mease is a consultant for and has received grant/research support from: abbvie, amgen, bristol-myers squibb, celgene, crescendo, eli lilly and company, genentech, janssen, merck, novartis, pfizer, ucb, is on the speaker’s bureau of: abbvie, amgen, bristol-myers squibb, celgene, crescendo, genentech, janssen, pfizer, and ucb ♦ this study was sponsored by eli lilly and company. medical writing services were provided by luke carey, phd, of proscribe – part of the envision pharma group, and were funded by eli lilly and company references 1. liu l, et al. j inflamm res. 2016;9:39-50. 2. mease p, et al. ann rheum dis. 2017;76:79-87. 3. mease p, et al. arthritis rheumatol. 2016;68 (suppl 10). 4. mease p, et al. ann rheum dis. 2016;75 (suppl 2). key eligibility criteria inclusion criteria ♦ male or female ≥18-years-old ♦ established diagnosis of active psoriatic arthritis ≥6 months and currently meets the caspar ♦ active psoriatic arthritis defined as the presence of ≥3 tender and ≥3 swollen joints ♦ ≥1 joint erosion on hand or foot x-rays or a c-reactive protein concentration >6 mg/l at screening • joint erosions were assessed by central reading ♦ active psoriatic skin lesion or a documented history of plaque psoriasis all ixe patients (starting ixe at weeks 0, 16, or 24) received a 160-mg starting dose (as two 80 mg injections) followed by 80 mg q2w or q4w; criteria for defining inadequate responders were blinded to investigators a plus rescue therapy (rt) in inadequate responders; b active reference arm ada=adalimumab; ixe=ixekizumab; pbo=placebo; r=randomization; rt=rescue therapy conclusions ♦ over a 52-week period, minimal changes in mtss were observed in patients with psoriatic arthritis who entered the extension period and were treated with ixekizumab 80 mg every 2 or 4 weeks objective ♦ to assess the impact of ixekizumab on the progression of structural joint damage in patients with psoriatic arthritis who were treated for up to 52 weeks in spirit-p1 study design spirit-p1 week 24: acr20 response rate and mtss change from baseline1 * p<.001 vs. placebo (acr20, logistic regression analysis; mtss, ancova) acr20=american college of rheumatology 20% response; ada=40 mg adalimumab every 2 weeks (active reference arm); ancova=analysis of covariance; ixe q2w=80 ixekizumab every 2 weeks; ixe q4w=80 mg ixekizumab every 4 weeks; itt=intent-to-treat; mtss=van der heijde modified total sharp score; nri=non-responder imputation; pbo=placebo; sd=standard deviation 1. mease p, et al. ann rheum dis. 2017;76:79-87. baseline demographics and disease characteristics, extension period population ixe q2w/ ixe q2w (n=96) pbo/ ixe q4w (n=45) ixe q4w/ ixe q4w (n=97) ada/ ixe q2w (n=48) ada/ ixe q4w (n=49) pbo/ ixe q2w (n=46) ixe q4w pbo (washout) pbo (washout) ixe q2w ixe q2w ixe q2w ixe q2w ixe q4w ixe q4w ixe q4w ixe q4w ixe q2w r rpbo r pbo (washout) + rta ixe q2w + rta ixe q4w + rta ixe q2w ixe q2w + rta ixe q4w ixe q4w + rta adab r pbo (washout) + rta screening extension perioddouble-blind treatment period week 0 week 16 week 24 week 32 week 52 pbo: placeboixe q4w: 80 mg ixe every 4 weeks ixe q2w: 80 mg ixe every 2 weeks ada: 40 mg ada every 2 weeksb 417 patients randomized 1:1:1:1 r adab (n=101) ixe q4w (n=107) ixe q2w (n=103) pbo (n=106) methods exclusion criteria ♦ current or prior use of biologic agents for treatment of psoriasis or psoriatic arthritis ♦ inadequate response to ≥4 cdmards ♦ current use (at study entry) of >1 cdmard ♦ serious infection within 3 months prior to randomization caspar=classification criteria for psoriatic arthritis; cdmard=conventional disease-modifying antirheumatic drug assessment of structural joint damage ♦ assessed using the van der heijde modified total sharp score (mtss) • quantifies the extent of bone erosions (20 locations per hand/wrist, 12 locations per foot) and joint space narrowing (20 locations per hand/wrist, 6 locations per foot) • total mtss score is the sum of bone erosion and joint space narrowing scores − scores range from 0 to 528 − higher scores represent greater damage ♦ x-rays at weeks 0, 24, and 52 were scored independently by two readers blinded to timepoint and clinical data • mtss scores represent the average score of the two readers statistical analysis ♦ extension period population • all patients who entered the extension period and received ≥1 dose of study medication during this period ♦ prespecified analysis • mtss data were excluded if the radiograph was taken after the scheduled visit date − presented as mean change from baseline to week 52 ♦ post hoc analysis • mtss data from radiographs taken after the scheduled visit date were interpolated − presented as mean change from baseline to week 52 • cumulative probability plots were created to visualize patient-level data • summaries are presented for the proportion of patients with no radiographic progression, defined as the mtss change from baseline to week 52 ≤ cut-off values of: 0.0, 0.5, and 1.32 (the smallest detectable change from baseline to week 52 in this study) ♦ missing data were imputed using linear extrapolation method if ≥1 postbaseline value was available mtss=van der heijde modified total sharp score results acr20 response rate at week 24, nri, itt population 0 2 0 4 0 6 0 8 0 1 0 0 r e s p o n s e ( % ) p b o ( n = 1 0 6 ) a d a ( n = 1 0 1 ; a c t i v e r e f e r e n c e a r m ) i x e q 4 w ( n = 1 0 7 ) i x e q 2 w ( n = 1 0 3 ) 30.2 57.4 57.9 62.1 * ** mtss change from baseline to week 24, linear extrapolation, itt population 0 1 2 3 m e a n c h a n g e f r o m b a s e li n e , s d p b o ( n = 1 0 6 ) a d a ( n = 1 0 1 ; a c t i v e r e f e r e n c e a r m ) i x e q 4 w ( n = 1 0 7 ) i x e q 2 w ( n = 1 0 3 ) baseline: 19.2 17.6 15.9 15.2 mean change: 0.170.49 0.11 0.07 pbo/ ixe q4w (n=45) pbo/ ixe q2w (n=46) ada/ ixe q4w (n=49) ada/ ixe q2w (n=48) ixe q4w/ ixe q4w (n=97) ixe q2w/ ixe q2w (n=96) age, years 50.5 (13.2) 51.0 (11.3) 50.0 (12.6) 46.2 (12.1) 48.7 (10.2) 49.6 (12.8) male, n (%) 19 (42.2) 23 (50.0) 21 (42.9) 30 (62.5) 40 (41.2) 44 (45.8) time since psa diagnosis, years 7.9 (7.6) 5.5 (6.5) 7.5 (7.8) 5.9 (5.6) 6.2 (6.5) 7.3 (8.3) background cdmard therapy, n (%) naïve 4 (8.9) 8 (17.4) 8 (16.3) 5 (10.4) 15 (15.5) 16 (16.7) past use 15 (33.3) 8 (17.4) 10 (20.4) 9 (18.8) 21 (21.6) 22 (22.9) current use 26 (57.8) 30 (65.2) 31 (63.3) 34 (70.8) 61 (62.9) 58 (60.4) tender joint count (68 joints) 18.5 (11.6) 19.2 (14.0) 18.8 (11.9) 18.8 (12.8) 20.8 (13.6) 21.3 (13.8) swollen joint count (66 joints) 9.6 (6.2) 10.7 (7.1) 10.1 (7.4) 9.6 (5.5) 11.0 (7.3) 12.2 (7.3) crp, mg/l 15.4 (29.5) 16.9 (20.4) 12.5 (12.7) 14.4 (24.7) 13.1 (17.0) 15.5 (26.7) mtss 11.5 (15.5) 24.5 (37.3) 15.6 (24.3) 15.4 (30.2) 19.6 (33.3) 15.2 (29.1) patients with erosions, n/nx (%) 44/45 (97.8) 45/45 (100.0) 44/48 (91.7%) 46/46 (100.0) 89/96 (92.7%) 92/96 (95.8%) data are mean (standard deviation) unless stated otherwise ada=40 mg adalimumab every 2 weeks (active reference arm); bmi=body mass index; cdmard=conventional diseasemodifying antirheumatic drug; crp=c-reactive protein; haq-di=health assessment questionnaire-disability index; ixe q2w=80 ixekizumab every 2 weeks; ixe q4w=80 mg ixekizumab every 4 weeks; mtss=van der heijde modified total sharp score; nx=number of patients with nonmissing values; pbo=placebo; psa=psoriatic arthritis mtss=van der heijde modified total sharp score acknowledgments ♦ the authors would like to thank: • all patients who participated in the study • all study investigators • justin grondines and ingrid burton from clinbay for providing programming support a post hoc analysis: data from radiographs taken after the scheduled visit date were interpolated; b 1.32 cut-off based on the sdc from baseline to week 52 in this study; ada=40 mg adalimumab every 2 weeks (active reference arm); ixe q2w=80 ixekizumab every 2 weeks; ixe q4w=80 mg ixekizumab every 4 weeks; mtss=van der heijde modified total sharp score; nx=number of patients with non-missing change from baseline data; sdc=smallest detectable change post hoc mtss, n (%) ada/ ixe q4w (nx=47) ada/ ixe q2w (nx=45) mtss ≤0 42 (89.4) 41 (91.1) mtss ≤0.5 42 (89.4) 43 (95.6) mtss ≤1.32 (sdcc) 43 (91.5) 44 (97.8) 2 0 4 0 6 0 8 0 1 0 0 5 0 5 1 0 1 5 2 0 c u m u l a t i v e p e r c e n t a g e c h a n g e f r o m b a s e li n e a d a / i x e q 4 w ( n x = 4 9 , n = 4 7 ) a d a / i x e q 2 w ( n x = 4 8 , n = 4 5 ) adalimumab/ixekizumab groups: mtss individual-patient change from baseline to week 52 cumulative probability plot, linear extrapolation,a extension period population ♦ on switching from adalimumab to ixekizumab, the majority of patients exhibited either no or minimal structural progression through 52 weeks of treatment placebo/ixekizumab groups: mtss individual-patient change from baseline to week 52 cumulative probability plot, linear extrapolation,a extension period population ♦ on switching from placebo to ixekizumab, the majority of patients exhibited either no or minimal structural progression through 52 weeks of treatment a post hoc analysis: data from radiographs taken after the scheduled visit date were interpolated; b 1.32 cut-off based on the sdc from baseline to week 52 in this study; ixe q2w=80 ixekizumab every 2 weeks; ixe q4w=80 mg ixekizumab every 4 weeks; mtss=van der heijde modified total sharp score; nx=number of patients with non-missing change from baseline data; pbo=placebo; sdc=smallest detectable change 2 0 4 0 6 0 8 0 1 0 0 5 0 5 1 0 1 5 2 0 c u m u l a t i v e p e r c e n t a g e c h a n g e f r o m b a s e li n e p b o / i x e q 4 w ( n x = 4 5 , n = 4 4 ) p b o / i x e q 2 w ( n x = 4 6 , n = 4 5 ) ₓ post hoc mtss, n (%) pbo/ ixe q4w (nx=44) pbo/ ixe q2w (nx=45) mtss ≤0 37 (84.1) 32 (71.1) mtss ≤0.5 40 (90.9) 33 (73.3) mtss ≤1.32 (sdcb) 41 (93.2) 40 (88.9) mtss change from baseline to week 52, linear extrapolation, extension period population ♦ the mtss change from baseline to week 52 was minimal for all groups (prespecified and post hoc analysis) a data were excluded if the radiograph was taken after the scheduled visit date; b data from radiographs taken after the scheduled visit date were interpolated ada=40 mg adalimumab every 2 weeks (active reference arm); ixe q2w=80 ixekizumab every 2 weeks; ixe q4w=80 mg ixekizumab every 4 weeks; mtss=van der heijde modified total sharp score; pbo=placebo; sd=standard deviation 1 0 1 2 3 m e a n c h a n g e f r o m b a s e li n e , s d p b o / i x e q 4 w ( n = 3 1 ) p b o / i x e q 2 w ( n = 3 7 ) i x e q 4 w / i x e q 4 w ( n = 8 0 ) i x e q 2 w / i x e q 2 w ( n = 8 0 ) a d a / i x e q 4 w ( n = 3 6 ) a d a / i x e q 2 w ( n = 3 4 ) baseline: 14.7 11.9 23.6 14.4 18.5 14.3 prespecified analysisa (data after visit excluded) mean change: 0.320.27 0.41 -0.03 0.54 0.09 1 0 1 2 3 m e a n c h a n g e f r o m b a s e li n e , s d p b o / i x e q 4 w ( n = 4 4 ) p b o / i x e q 2 w ( n = 4 5 ) i x e q 4 w / i x e q 4 w ( n = 9 7 ) a d a / i x e q 4 w ( n = 4 7 ) a d a / i x e q 2 w ( n = 4 5 ) i x e q 2 w / i x e q 2 w ( n = 9 6 ) post hoc analysisb (data after visit interpolated) 14.7 11.9 23.6 14.4 18.5 14.3 0.240.25 0.51 0.06 0.47 0.09 continuous ixekizumab groups: mtss individual-patient change from baseline to week 52 cumulative probability plot, linear extrapolation,a extension period population ♦ the majority of patients exhibited either no or minimal structural progression through 52 weeks of treatment with ixekizumab a post hoc analysis: data from radiographs taken after the scheduled visit date were interpolated; b 1.32 cut-off based on the sdc from baseline to week 52 in this study ixe q2w=80 ixekizumab every 2 weeks; ixe q4w=80 mg ixekizumab every 4 weeks; mtss=van der heijde modified total sharp score; nx=number of patients with non-missing change from baseline data; sdc=smallest detectable change 2 0 4 0 6 0 8 0 1 0 0 5 0 5 1 0 1 5 2 0 c u m u l a t i v e p e r c e n t a g e c h a n g e f r o m b a s e li n e i x e q 4 w / i x e q 4 w ( n x = 9 7 , n = 9 7 ) i x e q 2 w / i x e q 2 w ( n x = 9 6 , n = 9 6 ) post hoc mtss, n (%) ixe q4w/ ixe q4w (nx=97) ixe q2w/ ixe q2w (nx=96) mtss ≤0 79 (81.4) 81 (84.4) mtss ≤0.5 83 (85.6) 86 (89.6) mtss ≤1.32 (sdcb) 88 (90.7) 90 (93.8) fc17posterlillyvanderheijderadiographicprogression.pdf microsoft word july 2020 bar 683 proof returned.docx skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 353 brief articles interdigital tinea: the forerunner of infectious eczematoid dermatitis kyle r. bhatia1, robert t. brodell, md2, ashish c. bhatia, md3, chelsea s. mockbee, md2 1loyola university chicago, stritch school of medicine maywood, il 2department of dermatology, university of mississippi medical center jackson, ms 3department of dermatology, northwestern university, chicago, il case 1 is a male patient who presented with chronic scaling of the pedal interdigital spaces associated with mild intermittent pruritus. (figure 1a and 1b). case 2 is of a 28 year-old-male that presented with an acute onset erythematous eruption bilaterally on the feet. he had a long history of mildly pruritic and intermittently painful cracking between the fourth and fifth toes with associated thick, moist scaling. during a hunting trip, he walked through wetlands and wore his boots for two straight days, even while sleeping. when the boots were removed, he discovered a bilateral, tender, pruritic, weeping rash across his toes and distal foot. on physical exam, a well-demarcated, erythematous, oozing, edematous eruption with erosion was present on the plantar and dorsal surface of the feet and toes (figure 2a and 2b). figure 1. (a) scaling and erythema of the interdigital skin typical of tinea pedis. case presentation infectious eczematoid dermatitis (ied) is defined as an acute, eczematous eruption that occurs secondary to autosensitization to purulent drainage from a primary infected site. the condition is believed to develop when bacterial products, most often the result of staphylococcal or streptococcal species, act as haptens and stimulate an immune response. ied typically manifests as a plaque with associated vesicles and pustules surrounding drainage from a central infectious source, or as oozing, erythema, crusting, and scaling spreading peripherally from a central infectious source. management of ied includes both targeting the causative primary infection and suppressing the immune response producing a hypersensitivity reaction. this report details two cases. case 1 describes a common presentation of tinea pedis. case 2 is that of a 28 year-old-male who presented with an acute onset tender, pruritic, weeping rash after wearing boots for two straight days, and who was subsequently diagnosed and treated for ied. abstract skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 354 figure 1. (b) scaling of subdigital skin typical of tinea pedis. figure 2. oozing, erythematous eruption with interdigital and subdigital purulence overlying edematous toes of a male patient after two straight days without removing boots. table 1. diagnostic criteria for infectious eczematoid dermatitis as proposed by yamany and schwartz7. © 2014 european academy of dermatology and venereology reproduced with permission from john wiley and sons. clinical characteristics major criteria (2 of 2 must be present) 1. a primary infected lesion with purulent drainage. 2. eruption spreading peripherally from primary lesion. minor criteria (1 of 2 must be present) 1. peripheral vesicles and pustules with central oozing, crusting, and scaling. 2. oozing, crusting, and scaling throughout entirety of eruption. in case 1, the patient had a symbiotic relationship with a non-complicated tinea pedis infection, with fungal culture revealing trichophyton rubrum. tinea pedis is the most common dermatophytosis, affecting up to 25% of the population in the united states. it is most commonly associated with trichophyton rubrum, though epidermophyton, microsporum, and other trichophyton species have also been implicated.1 though dermatophytes are viewed as the causative organisms of tinea pedis, associated overgrowth of coinhabiting bacterial species is common, especially in more severe disease states.2 as disease severity increases, fungi are less frequently recoverable: fungi were demonstrated in 84% of mild and asymptomatic tinea pedis cases; 55% of moderately symptomatic cases; and 36% of severe cases. in these severe cases, increased rates of overgrowth of various bacterial species, including grampositive staphylococcus species and gramnegative proteus were found.3 these interdigital bacteria have higher rates of discussion skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 355 antibiotic resistance, which can be attributed to dermatophyte production of penicillin-like and streptomycin-like antibiotic substances.4,5 clinical presentation of intertriginous tinea pedis infection is highly variable. erythema, fissures, and pruritus may be present between the 4th and 5th toes, though some patients may be entirely asymptomatic. tinea pedis is typically treated with topical antifungals and hygiene measures to keep affected areas clean and dry. systemic antifungals may be used in severe or treatment-resistant cases.6 as the tinea is cleared, the bacterial component usually resolves without specific treatment. in case 2, a bacterial culture revealed staphylococcus aureus, while fungal culture was negative likely due to bacterial suppression of fungal growth. this patient’s presentation is consistent with infectious eczematoid dermatitis (ied). this condition is defined as an acute, eczematous eruption that occurs secondary to autosensitization to purulent drainage from a primary infected site.7 in a 1902 study of 1200 new patients to an outpatient dermatology clinic, engman reported that 35, or 2.9%, had presentations consistent with ied.8 a study at the mayo clinic examining inpatient dermatology admissions from 2000-2010 reported similar results, finding that 2.9% of 2216 admissions were due to ied.9 ied is believed to develop when purulent drainage from a primary infection causes autosensitization, with hypersensitivity developing as bacterial products act as haptens and stimulate an immune response.7 staphylococcal and/or streptococcal species are most commonly associated with ied.10 in this case, interdigital tinea pedis, and associated bacterial infection, flourished in the warm, moist environment of the patient’s wet boots over two days. an immune response stimulated the subsequent acute, eczematous eruption. the differential diagnosis for case 2 includes cellulitis and contact dermatitis. the clinical presentation of a pruritic and oozing, erythematous eruption was not consistent with cellulitis. though the eczematous eruption may have been attributed to contact dermatitis, the patient did not have a history of allergic contact dermatitis to leather or any other contactants. ied accounts for all aspects of the patient’s presentation, namely the initial fungal infection, secondary bacterial infection, and autosensitization and subsequent eczematous response. it is important to note that ied is distinct from auto-eczematization (dermatophytid or id reaction), a generalized process in which vesicles or pustules appear at distant sites in a patient with a localized tinea infection. these dermatophytid reactions may be the only presenting sign in an otherwise asymptomatic patient and typically resolve with treatment of the primary tinea infection.11 ied is a localized process that occurs adjacent to and surrounding the primary infectious locus.7 ied often initially presents as a plaque with associated vesicles and pustules surrounding a central source of infectious drainage. the lesion may spread peripherally, and older areas are distinguished by oozing, erythema, scaling, and crusting.7 alternatively, patients may present with oozing, erythema, crusting, and scaling that spreads peripherally from the central infectious source but with no evidence of vesicles or pustules.8 the patient from case 2 presented as the latter type. though ied can affect any part of the body, it is commonly found on the ears in patients with otitis externa, on the face and the nares in children with nasal skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 356 staphylococcus, and on the lower extremities in adults.12 in a 2015 comprehensive review of ied, yamany and schwartz proposed the major and minor diagnostic criteria found in table 1. the patient from case 2 met both the major criteria and the second minor criteria. the management of ied requires targeting the causative infection and suppressing the immune response producing a type iv hypersensitivity reaction. in addition, local wound care should be optimized. the patient’s primary tinea pedis infection was treated with oral terbinafine 250mg daily for 2 weeks. because of the severity of this condition, the secondary staphylococcal aureus infection was treated with oral doxycycline 100mg twice daily for 10 days. in order to quell the associated allergic contact dermatitis, the patient was placed on oral prednisone 60 mg [1 mg/kg], which was tapered off over 2 weeks. substantial improvement was noted in just 24 hours. local skin care included burrow’s solution applied three times daily, and the application of mupirocin ointment to promote barrier protection and fight superficial bacterial infection.7 the patient’s feet showed only post inflammatory erythema at 2 weeks. ketoconazole cream weekly between the toes was recommended to prevent recurrent tinea. conflict of interest disclosures: none funding: none corresponding author: robert t. brodell, md 106 chadwyck place madison, ms 39110 phone: 330-883-5302 fax: 601-984-1150 email: rbrodell@umc.edu references: 1. ilkit m, durdu m. tinea pedis: the etiology and global epidemiology of a common fungal infection. crit rev microbiol. 2015;41(3):374– 388. doi:10.3109/1040841x.2013.856853 2. gupta ak, skinner ar, cooper ea. interdigital tinea pedis (dermatophytosis simplex and complex) and treatment with ciclopirox 0.77% gel. int j dermatol. 2003;42 suppl 1:23–27. doi:10.1046/j.1365-4362.42.s1.1.x 3. leyden jj, kligman am. interdigital athlete's foot. the interaction of dermatophytes and resident bacteria. arch dermatol. 1978;114(10):1466– 1472. doi:10.1001/archderm.114.10.1466 4. youssef n, wyborn ch, holt g. antibiotic production by dermatophyte fungi. j gen microbiol. 1978;105(1):105–111. doi:10.1099/00221287-105-1-105 5. kates sg, nordstrom km, mcginley kj, leyden jj. microbial ecology of interdigital infections of toe web spaces. j am acad dermatol. 1990;22(4):578–582. doi:10.1016/01909622(90)70075-s 6. canavan tn, elewski be. identifying signs of tinea pedis: a key to understanding clinical variables. j drugs dermatol. 2015;14(10 suppl):s42–s47. 7. yamany t, schwartz ra. infectious eczematoid dermatitis: a comprehensive review. j eur acad dermatol venereol. 2015;29(2):203–208. doi:10.1111/jdv.12715 8. engman mf. an infectious form of an eczematoid dermatitis. st. louis courier of medicine 1902; 27: 401-414. 9. storan e, mcevoy m, wetter d, et al. experience with the dermatology inpatient hospital service for adults: mayo clinic, 2000–2010. j eur acad dermatol venereol. 2013;27:1360-1365. 10. slatkin mh. local use of bacitracin. j invest dermatol 1948; 10: 179-188. 11. weinstein a, berman b. topical treatment of common superficial tinea infections. am fam physician. 2002;65(10):2095–2102. 12. mcdaniel we, tamura j. auto-sensitization in infectious eczematoid dermatitis. ama arch derm syphilol. 1950;62(5):703–704. skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 328 brief article a rare presentation of angiolymphoid hyperplasia with eosinophilia involving the scrotum derrick adams do, faocd1, kevin mai, bs2 1 lassen medical center – red bluff 2 college of osteopathic medicine of the pacific, western university of health sciences pomona, ca angiolymphoid hyperplasia with eosinophilia (alhe) is an uncommon vascular proliferation. the wide histologic variations in presentation have spawned an equally wide degree of nomenclature of alhe. epitheliod hemangioma, pseudopyogenic granuloma, inflammatory angiomatous nodule, popular angioplasia, subcutaneous angioblastic lymphoid hyperplasia with eosinophilia and lymphofolliculosis, intravenous atypical vascular proliferation and histiocytoid hemangioma have all been utilized by various authors over the decades.1 the lesions of alhe are benign and typically present as papules or nodules on the face or neck.1 there is a slight predilection of females over males in alhe with most cases occurring between the ages of 20 and 50.2 it is likely an underreported condition, therefore, true demographic information may be lacking. clinically, alhe presents as pink to redbrown papules or nodules on the face or neck with a tendency to form in the preauricular area. alhe lesions often bleed easily and present as either asymptomatic or with pain, pruritis, or pulsations.3 renal disease and peripheral eosinophilia occur in a minority of patients.4 involvement of the oral mucosa, bone, muscle, parapharyngeal space, tongue, colon, and salivary glands are rare.5 there are less than 30 cases reported of male urogenital involvement. here we present the third reported case of alhe with scrotal involvement.6,7 a 17-year-old male with a history of refractory verrucous vulgaris presented for asymptomatic nodules on scrotum increasing in size and number over the last 3 years (figure 1). the patient denied any sexual history, pain, discharge, or trauma to the area. a biopsy was taken to rule out abstract angiolymphoid hyperplasia with eosinophilia (alhe) is a rare vascular proliferation that typically manifests as pink to reddish brown papules or nodules. these lesions classically affect the face or neck. involvement of other structures including the tongue, colon, salivary glands, and muscle are rare. male urogenital involvement for example, had less than 30 cases reported. here we present the third reported case of alhe involving the scrotum in a 17-year-old male. introduction case report skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 329 scrotal syringomas or steatocystoma multiplex. dense collections of lymphocytes with scattered histiocytes and eosinophils were appreciated in the dermis against a background of increased vasculature. microbial stains to rule out an infectious trigger were negative. angiolymphoid hyperplasia with eosinophilia was diagnosed. treatment options were discussed with the patient, but he has yet to decide upon a course of action. molecular clonality was not investigated due to cost constraints. figure 1. the first description of alhe was by wells and whimster in 1969.8 pathogenesis is unknown, but there is speculation that the lesions result from trauma to an artery or vein, infection, or from uncontrolled vascular factors.9 an estimated less than 10% of patients can recall a history of localized trauma or infection. in these cases, the median interval of lesion manifestation was 30 months.9 the results from a study of 53 out of 116 patients by olsen and helwig suggested that alhe may be caused by arteriovenous shunts.9 additionally, the patient’s history of refractory verruca vulgaris may provide further insight into the pathophysiology of alhe. since infections have been raised as a possible origin, might there be a possible association between hpv and alhe? our case also raises awareness for the spectrum of presentations alhe may manifest as when it involves the scrotum. compared to the other two known reported cases of alhe with scrotal involvement (figure 2), our case is the only one that presented bilaterally on the scrotum. hence, dismantling any notion of using unilateral/bilateral spatial arrangements as a possible differentiating factor when considering scrotal involvement of alhe. furthermore, when analyzed alongside previous cases, it appears alhe of the scrotum may vary in many other characteristics such as tenderness, pruritis and size. figure 2. case reports of angiolymphoid hyperplasia with eosinophilia have been inconsistent and underreported due to cases being incorrectly diagnosed as kimura’s disease (kd).9 while alhe and kd have similar characteristics, they are now characterized as different disorders.1,9 histologically, the main characteristic of alhe is vascular proliferation sometimes demonstrating cobble stoning with an eosinophil infiltrate.1 kd is generally deeper with lymphoid follicles, dense fibrosis, and an eosinophil infiltrate.1 alhe is a benign primary vascular proliferation, while kd is due to chronic inflammation and is either an allergic or autoimmune disorder.10 while a discussion skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 330 case report by chong et al presents a patient demonstrating features of both conditions simultaneously, the significance of this occurrence remains unknown.11 many treatment modalities have been used in attempts to clear alhe lesions, but it is notoriously refractory to current lines of treatment. surgical excision is often used after other non-invasive options have failed. other commonly used treatments include intralesional corticosteroids and laser therapy.3 lesions after surgical excision have a 33-50% recurrence rate. mohs micrographic surgery has also been used for treatment with results showing promise of completely resolving lesions with no recurrence and minimal destruction of healthy tissue.12 the high cost and exclusion criteria however preclude most patients from considering this option. other treatment modalities have included topical tacrolimus, electrocoagulation, corticosteroids, sclerotherapy, indomethacin, retinoids, cryotherapy, pentoxifylline, intravenous vinblastine sulfate, radiotherapy, interferon α-2b therapy, intralesional bleomycin, and radiofrequency excision.12 in conclusion, we are reporting only the third known case of scrotal angiolymphoid hyperplasia with eosinophilia. it is a rare but benign vascular proliferation that typically presents on the head or neck area. due to the high rates of recurrence, many treatment modalities have been used in attempts to clear lesions. conflict of interest disclosures: none funding: none corresponding author: kevin mai, bs college of osteopathic medicine of the pacific western university of health sciences pomona, ca email: kevin.mai@westernu.edu references: 1. chun si, ji hg. kimura's disease and angiolymphoid hyperplasia with eosinophilia: clinical and histopathologic differences. j am acad dermatol. dec 1992;27(6 pt 1):954-8. doi:10.1016/0190-9622(92)70293-o 2. azizzadeh m, namazi mr, dastghaib l, sariaslani f. angiolymphoid hyperplasia with eosinophilia and nephrotic syndrome. int j dermatol. mar 2005;44(3):242-4. doi:10.1111/j.1365-4632.2004.02030.x 3. adler bl, krausz ae, minuti a, silverberg ji, lev-tov h. epidemiology and treatment of angiolymphoid hyperplasia with eosinophilia (alhe): a systematic review. j am acad dermatol. mar 2016;74(3):506-12.e11. doi:10.1016/j.jaad.2015.10.011 4. ramchandani pl, sabesan t, hussein k. angiolymphoid hyperplasia with eosinophilia masquerading as kimura disease. br j oral maxillofac surg. jun 2005;43(3):249-52. doi:10.1016/j.bjoms.2004.11.023 5. tsuboi h, masuzawa m, katsuoka k. angiolymphoid hyperplasia with eosinophilia affecting the nail bed and underlying bone. j dermatol. jun 2006;33(6):399-402. doi:10.1111/j.1346-8138.2006.00094.x 6. chen jf, gao hw, wu by, tsai wc, chiang cp. angiolymphoid hyperplasia with eosinophilia affecting the scrotum: a rare case report with molecular evidence of t-cell clonality. j dermatol. apr 2010;37(4):355-9. doi:10.1111/j.1346-8138.2010.00818.x 7. park j, hwang sr, song kh, kim ji, rhee ch, yun sk. angiolymphoid hyperplasia with eosinophilia affecting the scrotum of a child. eur j dermatol. 2013 may-jun 2013;23(3):423-4. doi:10.1684/ejd.2013.2051 8. wells gc, whimster iw. subcutaneous angiolymphoid hyperplasia with eosinophilia. br j dermatol. jan 1969;81(1):1-14. doi:10.1111/j.1365-2133.1969.tb15914.x 9. olsen tg, helwig eb. angiolymphoid hyperplasia with eosinophilia. a clinicopathologic study of 116 patients. j am acad dermatol. may 1985;12(5 pt 1):781-96. doi:10.1016/s0190-9622(85)70098-9 conclusion skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 331 10. dargent jl, vannuffel p, saint-remy jm, fisogni s, facchetti f. plasmacytoid dendritic cells in kimura disease. am j dermatopathol. dec 2009;31(8):854-6. doi:10.1097/dad.0b013e3181a772c6 11. chong ws, thomas a, goh cl. kimura's disease and angiolymphoid hyperplasia with eosinophilia: two disease entities in the same patient: case report and review of the literature. int j dermatol. feb 2006;45(2):13945. doi:10.1111/j.1365-4632.2004.02361.x 12. miller cj, ioffreda md, ammirati ct. mohs micrographic surgery for angiolymphoid hyperplasia with eosinophilia. dermatol surg. aug 2004;30(8):1169-73. doi:10.1111/j.15244725.2004.30349.x skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 848 short communication total skin electron beam therapy-induced erythrodermic subacute radiation dermatitis in a 54-year-old man with underlying cutaneous t-cell lymphoma arthur m. samia, md1, frank a. lacy, md2, sam b. wu, md2, carolyn m. ziemer, md, mph2 1 the university of florida department of dermatology, gainesville, fl 2 the university of north carolina department of dermatology, chapel hill, nc radiation dermatitis is one possible side effect of external beam ionizing radiation, which encompasses several radiotherapy modalities used to combat underlying malignancies. one modality in particular – total skin electron beam therapy (tsebt) – has been shown to produce clinically meaningful responses in advanced-stage mycosis fungoides (mf).1 though less toxic than conventional-dose modalities, dermatologic toxicities may occur following low-dose tsebt. we highlight a case of a patient transferred to our institution for the management of subacute radiation dermatitis (srd) mimicking stevens-johnson syndrome following low-dose tsebt for mf. the patient’s mf was being managed by his radiation oncologist at an outside hospital and the most recent staging of his disease three years prior was t2n0 disease without evidence of hematologic involvement. there was no record of pet/ct imaging upon admission. he presented with exfoliative erythroderma with areas of full-thickness epidermal loss over the trunk and extremities (figures 1 and 2). there was prominent, diffuse, background, mottled hyper-, hypo-, and depigmentation. the vermillion lips had erythema and hemorrhagic crust but no further mucosal involvement. no lymphadenopathy was appreciated. skin biopsy was supportive of srd without evidence of lymphoma. flow cytometry supported the absence of sézary syndrome (ss). thirteen days prior to admission, the patient initiated a course of low-dose tsebt with a receipt of 1050 cgy over seven nonconsecutive days. however, three years prior to admission, the patient underwent a first course of conventional-dose tsebt totaling 3600 cgy, for a cumulative radiation dose of 4650 cgy. in addition to tsebt, prior treatments included topical and oral steroids, interferon, and psoralen ultraviolet a therapy. after the diagnosis of srd was made, discontinuation of tsebt was recommended and the patient was managed with wound care and supportive therapies as well as topical steroids for inflamed areas. this resulted in significant improvement in erythema and desquamation. low-dose tsebt has become increasingly favorable due to its side effect profile and can be particularly effective in patients with treatment-refractory ss.2 however, it is important for dermatologists to recognize and be mindful that the toxicity of tsebt is skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 849 subject to a patient’s cumulative radiation dose.3 additionally, a review of the literature suggests cessation of radiation therapy, appropriate wound care, and topical corticosteroids are mainstays of treatment for srd.4 cetuximab therapy should be considered in extreme cases until symptomatic control.5 in patients with srd, monitoring for secondary infection of the skin is a critical concern.6 overall, this case is a rare presentation of radiation dermatitis presenting as erythroderma and highlights the importance of appropriate consideration of these adverse events in patients receiving tsebt. figure 1. exfoliative erythroderma with areas of fullthickness epidermal loss over the trunk and extremities figure 2. dorsal view. consent: the patient provided consent to use the photos included in the publication. conflict of interest disclosures: none funding: none corresponding author: arthur m. samia, md university of florida department of dermatology email: samiaa17@students.ecu.edu references: 1. chowdhary m, chhabra am, kharod s, marwaha g. total skin electron beam therapy in the treatment of mycosis fungoides: a review of conventional and low-dose regimens. clin lymphoma, myeloma leuk. 2016. doi:10.1016/j.clml.2016.08.019 2. durgin js, jariwala nn, wysocka m, et al. low-dose total skin electron beam therapy as part of a multimodality regimen for treatment of sézary syndrome: clinical, immunologic, and molecular analysis. jama dermatology. 2020. doi:10.1001/jamadermatol.2020.3958 3. kamstrup mr, lindahl lm, gniadecki r, et al. low-dose total skin electron beam therapy as a debulking agent for cutaneous t-cell lymphoma: an open-label prospective phase ii study. br j dermatol. 2012. doi:10.1111/j.1365-2133.2011.10670.x 4. bernier j, bonner j, vermorken jb, et al. consensus guidelines for the management of radiation dermatitis and coexisting acne-like rash in patients receiving radiotherapy plus egfr inhibitors for the treatment of squamous cell carcinoma of the head and neck. in: annals of oncology : official journal of the european society for medical oncology / esmo. ; 2008. doi:10.1093/annonc/mdm400 5. bernier j, russi eg, homey b, et al. management of radiation dermatitis in patients receiving cetuximab and radiotherapy for locally advanced squamous cell carcinoma of the head and neck: proposals for a revised grading system and consensus management guidelines. ann oncol. 2011. doi:10.1093/annonc/mdr139 6. lloyd s, chen z, foss fm, girardi m, wilson ld. acute toxicity and risk of infection during total skin electron beam therapy for mycosis fungoides. j am acad dermatol. 2013. doi:10.1016/j.jaad.2013.04.063 skin march 2018 volume 2 issue 2 copyright 2018 the national society for cutaneous medicine 144 brief articles a rare presentation of toxic epidermal necrolysis-like acute systemic lupus erythematosus brandon t. beal md a , taryn blaha ba b , david d. xiong ba c , sarah h. schneider md a , steven d. billings md d , anthony p. fernandez md phd a,d , shilpi khetarpal md a a department of dermatology, cleveland clinic, cleveland, oh b northeast ohio medical university, rootstown, oh c lerner college of medicine, cleveland clinic, cleveland, oh 4 department of dermatopathology and anatomic pathology, cleveland clinic, cleveland, oh acute systemic lupus erythematosus presenting as toxic epidermal necrolysis (ten-like asle) is rare with less than 25 reported cases. 1 differentiating asle and ten can be difficult, as both share clinical and histological findings such as diffuse desquamation, mucosal erosions, and keratinocyte necrosis. prodromal systemic symptoms (fatigue, myalgias, and polyarthritis), positive ana and ena, photodistributed eruption, and a prolonged disease course characterize asle, while an identifiable trigger and more acute onset (less than 9 days) favor ten. histopathologically, vacuolar interface change, limited keratinocyte apoptosis, abstract a 25-year-old woman with a history of systemic lupus erythematosus (sle) was transferred from an outside hospital with a worsening painful generalized rash and oral ulcerations for the prior three weeks due to concern for stevens-johnson syndrome / toxic epidermal necrolysis. exam revealed denuded erythematous plaques covering over 80% of the patient’s body surface area and a 4.2 x 2.6 cm ulcerated plaque of the superior hard palate. histology demonstrated parakeratosis and compact hyperkeratosis overlying an atrophic epidermis with vacuolar interface change, prominent keratinocyte dyskeratosis, and a thickened basement membrane zone (bmz). the superficial dermis had a mild predominantly lymphocytic perivascular infiltrate and superficial dermal mucin deposition. direct immunofluorescence was positive for igg (granular, bmz), c3 (granular, bmz), and iga was negative. labs were remarkable for positive ana (1:160), ds-dna, anti-smith, antirnp, low c3/c4, with negative anti-ssa/ssb. the clinicopathological correlation was most consistent with the diagnosis of ten-like acute systemic lupus erythematosus. our patient improved with treatment for her acute systemic lupus erythematosus. this case highlights a challenging clinicopathologic differential diagnosis. introduction skin march 2018 volume 2 issue 2 copyright 2018 the national society for cutaneous medicine 145 dense lymphocytic infiltrate, and dermal mucin suggest alse, whereas a basketweave stratum corneum, sparse lymphocytic infiltrate, and full thickness epidermal necrosis are consistent with ten. 1-5 a 25-year-old woman with a history significant for systemic lupus erythematosus (sle) was transferred from an outside hospital with a worsening painful generalized rash and oral ulcerations for the prior 3 weeks due to concern for stevensjohnson syndrome / toxic epidermal necrolysis. prior to admission, she noted a diffuse and painful rash, large oral ulcerations, fatigue, and muscle/joint pain. initial evaluation revealed an ill-appearing female of fitzpatrick skin type i. involving approximately 80 % body surface area (bsa), including the face, torso, arms, and legs, were diffuse confluent eroded erythematous reticulated plaques with palmar and plantar sparing (figure 1). case report figure 1. generalized eroded, erythematous plaques of the chest (a), trunk (b), and back (c) coalescing into larger plaques involving approximately 80% body surface area. a b c skin march 2018 volume 2 issue 2 copyright 2018 the national society for cutaneous medicine 146 examination of the mouth revealed a 4.2 x 2.6 cm ulcerated plaque on the superior hard palate (figure 2). a lesional punch biopsy was performed showing areas of parakeratosis and compact hyperkeratosis overlying an atrophic epidermis with vacuolar interface change and prominent keratinocyte dyskeratosis and apoptosis. the basement membrane was thickened. within the superficial dermis, there was a mild, predominantly lymphocytic perivascular infiltrate. there was also superficial dermal mucin deposition. these findings were most consistent with an interface dermatitis (figure 3). direct immunofluorescence was positive for igg (granular, bmz) and c3 (granular, bmz), and iga negative. labs were remarkable for positive ana (1:160), ds-dna, anti-smith, anti-rnp, low c3/c4, with negative antissa/ssb. the clinicopathological correlation was most consistent with the diagnosis of ten-like asle. our patient improved with a loading dose of hydroxychloroquine, 200mg three times daily for three months following by 5mg/kg/day thereafter, methylprednisone 1g iv every 24 hours for the first three days and then she was transitioned to oral prednisone 60mg daily which was tapered over approximately 6 months, mycophenolate mofetil 1g twice daily, and dapsone 100mg daily. figure 2. clinical image demonstrating a 4.2x2.6 cm ulcerated plaque on the superior hard palate. skin march 2018 volume 2 issue 2 copyright 2018 the national society for cutaneous medicine 147 figure 3. histologic sections demonstrating parakeratosis and compact hyperkeratosis overlying an atrophic epidermis with vacuolar interface change (a), prominent keratinocyte dyskeratosis and apoptosis (b). within the superficial dermis, there is a mild, predominantly lymphocyctic perivascular infiltrate and mucin deposition. a b skin march 2018 volume 2 issue 2 copyright 2018 the national society for cutaneous medicine 148 ten-like asle is rare. ten is characterized by erythema with severe necrosis and desquamation of the epidermis and epithelia of mucous membranes with greater than 30% bsa involvement. the onset is typically acute, with maximal extension of lesions within hours to days. 2 both asle and ten are inflammatory and interface dermatoses, and share clinical and pathologic findings such as generalized desquamation, mucosal erosions, and keratinocyte necrosis. 1 prodromal systemic symptoms, positive ana and ena, photodistributed eruption, and a prolonged disease course characterize asle 3-5 whereas an identifiable trigger and more acute onset (less than 9 days) favor ten. 1 histologically, vacuolar interface change, limited keratinocyte apoptosis, dense lymphocytic infiltrate, and dermal mucin suggest alse, while a basket-weave stratum corneum, sparse lymphocytic infiltrate, and full thickness epidermal necrosis are more consistent with ten. 1 there is both clinical and histological overlap of asle and ten. differentiating these two entities has practical and important implications for patients, treatment, and counseling. we present a rare case of ten-like asle that required treatment with systemic immunomodulatory and immunosuppressant medications. this case highlights a challenging clinicopathologic differential diagnosis important for dermatologists and dermatopathologists to be aware of. conflict of interest disclosures: none. funding: none. corresponding author: brandon t. beal, md department of dermatology, cleveland clinic 9500 euclid ave/a61 cleveland, oh 44195 216-444-5572 (office) 216-636-0435 (fax) bealb@ccf.org references: 1. ziemer m, kardaun sh, liss y, et al. stevens-johnson syndrome and toxic epidermal necrolysis in patients with lupus erythematosus: a descriptive study of 17 cases from a national registry and review of the literature. br j dermatol. 2012 mar;166(3):575-600. 2. mandelcorn r, shear n. lupusassociated toxic epidermal necrolysis: a novel manifestation of lupus? j am acad dermatol. 2003;48(4):525-29. 3. tiao j, reng r, carr k et al. using the american college of rheumatology (acr) and systemic lupus international collaborating clinics (slicc) criteria to determine the diagnosis of systemic lupus erythematosus (sle) in patients with subacute cutaneous lupus erythematosus (scle). j am acad dermatol. 2016 may;74(5):862-9. discussion conclusion skin march 2018 volume 2 issue 2 copyright 2018 the national society for cutaneous medicine 149 4. ting w, stone ms, racila d, scofield rh, sontheimer rd. toxic epidermal necrolysis-like acute cutaneous lupus erythematosus and the spectrum of the acute syndrome of apoptotic panepidermolysis (asap): a case report, concept review and proposal for new classification of lupus erythematosus vesiculobullous skin lesions. lupus. 2004;13:941-50. 5. yildirim cg, sayar h, ozkan f, et al. a case of toxic epidermal necrolysis-like skin lesions with systemic lupus erythematosus and review of the literature. lupus. 2013 jul;22(8):83946. conclusion resultsabstract methods introduction ozenoxacin is a non-fluorinated quinolone antibiotic with potent activity against grampositive bacteria, being developed as a 1% cream for the topical treatment of impetigo. objectives the primary objective of the study was to compare the efficacy and evaluate the safety and tolerability of ozenoxacin 1% cream versus vehicle after 5 day bid topical applications (10 applications) in patients with impetigo. retapamulin 1% ointment was included as an active control. methods a phase 3 multicenter, randomized, vehicleand active-controlled, parallel, double-blind clinical trial in patients aged 2 years and older with impetigo. patients were randomized in a 1:1:1 ratio to ozenoxacin, vehicle, or retapamulin. efficacy was evaluated utilizing a clinical skin infection rating scale (sirs) and microbiological culture. safety and tolerability were also evaluated. results after 5 days of therapy, ozenoxacin demonstrated clinical superiority to vehicle. ozenoxacin also demonstrated superior microbiological success compared to vehicle as early as after 2 days of treatment. in addition, ozenoxacin demonstrated superior microbiological success to retapamulin after 2 days. ozenoxacin was safe and well tolerated. conclusions ozenoxacin demonstrated superior clinical and microbiological response compared to vehicle and presented a favorable safety and tolerability profile. ozenoxacin also demonstrated early microbiological superiority versus both vehicle and retapamulin. ozenoxacin represents a novel topical therapeutic option being developed for the treatment of impetigo. • a total of 465 patients were enrolled into the study (3 sites in the usa, 4 sites in germany, 2 sites in romania, 5 sites in ukraine, and 13 sites in south africa). • eligible patients were randomized to receive ozenoxacin 1% cream (155 patients), vehicle (156 patients), or retapamulin 1% ointment (154 patients) applied topically bid for 5 days to all impetigo affected areas, with a maximum extension of 100 cm2. the first application was done under the guidance of the delegated person appointed by the investigator. after randomization, patients returned at: visit 2 (day 3-4, on-therapy) and visit 3 (during the following day after last application, day 6-7, end of therapy). patients returned for a final visit (visit 4, day 10-13). additionally, a telephone contact on day 2 (24-36 hours after baseline visit) was required to assess for any worsening of infection. • the primary efficacy endpoint was clinical response (success or failure) at end of therapy (visit 3) analyzed in the intent-to-treat clinical (ittc) population. • success at visit 3 was defined as sirs score 0 for exudates/pus, crusting, tissue warmth and pain and no more than 1 each for erythema/inflammation, tissue oedema and itching and no additional antimicrobial therapy on the baseline affected area(s) necessary. • main secondary efficacy endpoints were clinical response at all visits in all study populations and microbiological response (success or failure) at all visits in the bacteriological population. • the evaluation of safety was based on the assessment of adverse events (type, nature, incidence and outcome) and changes in clinical laboratory parameters (hematology, clinical chemistry, urinalysis), vital signs and physical examination. • for all efficacy analyses, the primary treatment comparison of interest was ozenoxacin versus vehicle, to test the superiority of ozenoxacin versus vehicle. a secondary comparison (for internal validity) of retapamulin versus vehicle was done for the analysis of clinical response (clinical success or clinical failure) at the end of therapy visit (visit 3) in the ittc population. in summary, in a randomized controlled trial of 465 patients that included adults and children ages 2 years and older with impetigo, ozenoxacin demonstrated superior clinical and microbiological response versus vehicle after 5 days of therapy, and was safe and well tolerated. ozenoxacin also demonstrated microbiological superiority versus retapamulin after 2 days of treatment. ozenoxacin represents a novel topical therapeutic option being developed for the treatment of impetigo. table 1. primary endpoint clinical response at end of therapy (visit 3, day 6-7) (ittc population) p880 ozenoxacin placebo retapamulin n 155 156 154 clinical success 54 (34.8%) 30 (19.2%) 58 (37.7%) clinical failure 98 (63.2%) 120 (76.9%) 91 (59.1%) unable to determine 3 (1.9%) 6 (3.8%) 5 (3.2%) p-value (vs placebo) 0.003 <0.001 ozenoxacin demonstrated a statistically significant superior clinical response compared to vehicle at end of treatment. the results for retapamulin were also superior to vehicle and similar to ozenoxacin. table 2. combined criteria of clinical success at end of therapy (visit 3, day 6-7) (randomized patients) p880 ozenoxacin placebo retapamulin n 155 156 154 clinical success 132 (85.2%) 115 (73.7%) 128 (83.1%) clinical failure 21 (13.5%) 36 (23.1%) 24 (15.6%) unable to determine 2 (1.3%) 5 (3.2%) 2 (1.3%) p-value (vs placebo) 0.0276 the analysis of combined criteria of clinical success (posthoc) was defined as a total absence of the treated lesions (lesion extension=0) or the treated lesions became dry without crusts compared to baseline (sirs=0 for exudate and for crusting), or improvement (defined as decline in the size of the affected area, number of lesions or both) such that no further antimicrobial therapy was necessary. this broader definition of clinical success includes improvement, and reflects the same criteria for clinical success as that used in pivotal phase 3 clinical trials of other topical antibiotics approved for impetigo. overall, 7.5% of patients experienced at least 1 adverse event (ae) and the incidences were generally similar across treatment groups. most aes were of mild intensity and only 2 (application site pain and urticaria) both in the retapamulin group were considered to be possibly related to study medication. there were no clinically relevant changes in laboratory hematology, clinical chemistry or urinalysis, or in vital signs. table 3. microbiological response at visit 2 (day 3-4) and at end of therapy (visit 3, day 6-7) (ittb population) p880 ozenoxacin placebo retapamulin visit 2, day 3-4 n 154 152 153 microbiological success 109 (70.8%) 58 (38.2%) 86 (56.2%) microbiological failure 37 (24.0%) 90 (59.2%) 60 (39.2%) unable to determine 8 (5.2%) 4 (2.6%) 7 (4.6%) p-value (vs placebo) <0.0001 p-value (vs retapamulin) 0.0087* visit 3, day 6-7 n 154 152 153 microbiological success 122 (79.2%) 86 (56.6%) 124 (81.0%) microbiological failure 16 (10.4%) 55 (36.2%) 18 (11.8%) unable to determine 16 (10.4%) 11 (7.2%) 11 (7.2%) p-value (vs placebo) <0.0001 * statistical significance confirmed post-hoc ozenoxacin demonstrated a statistically significant superior microbiological response compared to vehicle at visit 2 (day 3-4) and at end of treatment (visit 3). ozenoxacin demonstrated superior microbiological success compared to retapamulin after 2 days. this poster and study was funded by medimetriks pharmaceuticals, inc. and ferrer internacional sa pp1483-r4 a randomized vehicle-controlled trial to assess the efficacy, safety and tolerability of ozenoxacin 1% cream in 465 patients 2 years and older with impetigo n. albareda1, j. zeichner2 1 ferrer, barcelona, spain; 2 mount sinai school of medicine, nyc fc17postermedimetriksalbaredarandomized465patients.pdf skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 291 clinical management recommendations appropriate use criteria for the integration of diagnostic and prognostic gene expression profile assays into the management of cutaneous malignant melanoma: an expert panel consensus-based modified delphi process assessment brian berman, md, phd1, roger ceilley, md2, clay cockerell, md, mba3, laura ferris, md4, whitney a high, md, jd, meng5, mark lebwohl, md6, mark s nestor, md, phd1, theodore rosen, md7, graham h litchman, do, ms8, giselle prado, md8, ryan m svoboda, md, ms9, darrell s rigel, md, ms10 (melanoma gep consensus-based recommendation panel) 1department of dermatology & cutaneous surgery, university of miami miller school of medicine, miami, fl 2department of dermatology, the university of iowa, iowa city, ia 3department of dermatopathology, university of texas southwestern medical center, dallas, tx 4department of dermatology, university of pittsburgh medical center, pittsburgh, pa 5department of dermatology and pathology, university of colorado school of medicine, aurora, co 6department of dermatology, icahn school of medicine at mount sinai, new york, ny 7department of dermatology, baylor college of medicine, houston, texas 8national society for cutaneous medicine, new york, ny 9department of dermatology, duke school of medicine, durham, nc 10department of dermatology, nyu school of medicine, new york, ny the last century has seen a vast increase in the incidence of malignant melanoma, both in the united states and worldwide.1 in 2019, an estimated 96,480 cases of invasive melanoma will be diagnosed in the united states alone, resulting in over 7,000 deaths.2 advances in basic and translational research are essential in addressing this public health challenge. developments in molecular biology and genomics are rapidly expanding the armamentarium of diagnostic and therapeutic tools available to facilitate the management of melanoma patients.3 a deeper understanding of patterns of gene expression in melanoma lesions has resulted in the development of novel tests designed to both aid in the diagnosis of melanoma and to provide additional prognostic information in confirmed cases. these gene expression profiling (gep) assays utilize a quantitative reversetranscriptase polymerase chain reaction (qrt-pcr) to determine the level of expression of key groups of signature genes.4-6 the utility of diagnostic and prognostic gep technology is based upon the fact that the level of expression of key genes varies between benign and malignant pigmented lesions and between malignant melanomas with lower and higher propensity for subsequent metastasis, respectively.4-6 depending on the specific test being utilized, the results can aid in the decision to biopsy equivocal pigmented lesions6, assist dermatopathologists in determining a diagnosis in cases of challenging skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 291 292 histopathology7, and provide managing clinicians with further prognostic information in cases of biopsy-proven melanoma.4 in 2018, three validated, us governmentally approved, commercially available gep tests were each incorporated into melanoma patient management over 10,000 times in the united states.8-11 despite the magnitude of melanoma gep test utilization, current melanoma management guidelines— including those recently put forward by the american academy of dermatology (aad)— fail to provide guidance regarding the use of these assays across specific clinical situations.12 given the existing knowledge gap and the high current magnitude of utilization of these tests, there is a critical need for an evidence-based consensus statement. to meet this need, a panel of dermatologists/dermatopathologists with expertise in pigmented lesions, knowledge of the melanoma-related gep literature, and/or experience with appropriate use criteria (auc) consensus development was convened to systematically review the available evidence surrounding cliacertified gep diagnostic and prognostic tests. the objective of this expert panel was to develop a set of consensus-based auc recommendations to guide the integration of gep technology into the diagnosis and management of melanoma in specificallydefined situations commonly encountered in clinical practice. selection of gep assays for inclusion it was specified a priori that these recommendations would pertain to clinically diagnostic, histologically diagnostic, or prognostic gep assays for melanoma that were validated, us governmentally approved for clinical use, readily available, and with existing widespread usage at the time the expert panel was convened. this led to selection of three gep assays which met inclusion criteria: the 2-gep test6 (pigmented lesion assay, dermtech, la jolla, ca), the 23-gep test5 (mypath®, myriad genetics, inc., salt lake city, ut), and the 31-gep test4 (decisiondx™melanoma, castle biosciences, inc., friendswood, tx). gep augmenting melanoma clinical diagnosis the 2-gep test is an adjunctive diagnostic assay used to aid the clinician in the decision to biopsy in cases of clinically and/or dermoscopically equivocal pigmented lesions. genetic material (in the form of rna) is harvested from the lesion in question by an adhesive patch. the rna is then reverse-transcribed to dna and amplified using qrt-pcr to determine rna expression levels of two key genes: long intergenic non-protein coding rna 518 (linc00518) and melanoma antigen preferentially expressed in tumors (prame).6 the method is non-invasive and yields a low, moderate, or high-risk result for each lesion tested. this result is then considered in the context of lesion morphology, clinical history, and data from other adjunctive tests to determine if biopsy or continued observation is warranted. gep augmenting melanoma histopathological diagnosis the 23-gep test is a diagnostic assay utilized by dermatopathologists to aid in rendering a final diagnosis in cases where histopathologic features alone cannot fully distinguish between benign and malignant melanocytic lesions.5 rna is extracted from formalin-fixed, paraffin-embedded biopsy methods skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 291 293 specimens and qrt-pcr is used to assess expression of 23 key genes. these genes, involved in cell differentiation, cell-cell signaling, and immune response, have expression patterns which vary between benign nevi and malignant melanoma in a predictable manner. the results are combined into a single score ranging from 16.7 through 11.1, with groupings corresponding to benign, indeterminate, or consistent with malignant melanoma.5 gep augmenting assessment of melanoma prognosis the 31-gep test, as opposed to the 2-gep and 23-gep assays, is used to help determine prognosis in patients with earlystage invasive cutaneous melanoma. after extraction of rna from formalin-fixed, paraffin-embedded excision specimens of primary melanoma, the level of expression of 31 genes (28 prognostic genes) is quantified using qrt-pcr and used to stratify patients into low-risk (class 1a and 1b) and high-risk (class 2a and 2b) groups based on probability of subsequent metastasis.13,14 the results of this test have been shown to be synergistic with existing risk-stratification tools identifying patients with high-risk tumors.13,15 literature search a thorough systematic review of the literature pertaining to the use of the 2-, 23-, and 31-gep tests was conducted. the goal of this search was to identify studies evaluating either clinical validity, outcomes, or utility for level of evidence review and development of recommendations by the expert panel. the medline database was queried for all relevant articles published between 1940 and 2018 using exploded mesh terms and keywords pertaining to the following themes: gene expression profiling, diagnosis, prognosis, and molecular genomics. the boolean term “and” was used to find the intersection of these themes with the term “cutaneous melanomas.” the initial search identified potentially relevant articles, which were each distributed to reviewers who independently screened for relevance and appropriateness for inclusion. the articles that remained were then assessed in depth to determine relevance to the study objective and final eligibility. discrepancies between the independent reviewers were resolved through team discussion. articles deemed relevant to one of the three gep tests being evaluated based on full-text review were selected for level of evidence analysis by members of the consensus panel. development of consensus-based auc recommendations an initial list of potential indications for the use of each gep test was created based on review of the pertinent articles identified through the literature search as well as the clinical experience of a core group of experts. this list was meant to encompass a broad selection of clinical scenarios commonly faced by practicing dermatologic surgeons and dermatopathologists in the diagnosis and management of melanocytic lesions. the purpose was to identify common scenarios in which utilization of gep tests might be considered so that the existing literature could be assessed for evidence supporting or refuting their use in each situation. this list was not meant to be inclusive of every possible situation for which the use of the 2-, 23-, or 31-gep tests could be considered, but was meant to cover a wide range of the most common scenarios. after initial creation of the list of indications for each gep assay, each member of the consensus panel had an skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 291 294 opportunity to review and propose modifications of the draft indications. level of evidence assessment and consensus recommendation process a consensus panel of nine expert dermatologists/dermatologic surgeons/dermatopathologists selected for their knowledge of the tests being evaluated and the associated literature, their expertise in managing pigmented lesions, and/or their recognized academic excellence was convened in person in august 2018, to determine the individual level of evidence for each of the selected publications as well as an overall strength of recommendation for each indication using standard strength of recommendation taxonomy (sort) methodology.16 the selected articles were made available for individual review prior to the consensus meeting. additionally, a reference offering an overview of the sort framework16 was provided and a brief lecture on evidence-based medicine and sort methodology was delivered to members of the expert panel. consensus among panel members regarding level of evidence for each article and strength of recommendation for each recommendation was achieved using a modified delphi technique.17 this methodology has been used extensively in the literature to yield recommendations for dermatologists.18-20 consensus was defined as agreement among at least a supermajority of 2/3 of the experts participating in the panel. if 2/3 agreement could not be achieved, the proposal was rediscussed among panel members and modified until agreement was achieved. comprehensive literature search the initial literature search produced 524 articles. after review of articles deemed potentially relevant, 33 articles which measured the clinical validity, relevance, efficacy, and/or utility of the gep tests were designated for distribution to the full consensus panel. of the 33 relevant published articles identified, 8 pertained to the 2-gep test6,21-27, 10 were pertinent to the 23-gep test5,7,28-35, and 15 were germane to the 31-gep test13-15,36-47 (tables 1-3). levels of evidence of selected articles where applicable, sort guidelines were utilized to assign a level of evidence to each article based on consensus of the expert panel as outlined previously (tables 1-3). of the 8 articles pertaining to the 2-gep test, 2 were determined by expert panel consensus to represent level 3 evidence25,26, 2 were deemed consistent with level 2 evidence21,22, and 2 were felt to represent level 1 evidence6,23. two articles were not assigned levels of evidence because after group discussion, consensus deemed their content irrelevant to the generated list of recommendations.10,27 based on the consensus of the expert panel, 2 of the 10 articles pertaining to the 23-gep test were felt to represent level 3 evidence33,35, 4 were deemed to be consistent with level 2 evidence7,30,31,34, and 3 were determined to be level 1 evidence.5,29,32 one article was not assigned a level of evidence because it was deemed irrelevant to the current study.28 results skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 291 295 regarding the published articles detailing the 31-gep test, 3 out of 15 were deemed to represent level 3 evidence37,40,46, 9 were classified as level 2 evidence14,15,36,38,41,42,44,45,47, and 2 graded as level 1 evidence13,43. upon discussion by the expert panel, 1 article was deemed to be outside of the context of the panel and thus was not assigned a level of evidence.39 overall, consensus opinion was reached on the strength of recommendation for 29 recommendations involving the use of diagnostic and prognostic gene expression profiling tests in the diagnosis and management of melanoma (tables 4-6). consensus-based auc recommendations for the 2-gep test of the 7 recommendations considered for the 2-gep test (table 4), 1 was deemed to represent a b-strength recommendation for the use of the 2-gep assay: • cases in which patients present with atypical lesions requiring additional assessment beyond inspection in order to aid in the biopsy decision six were deemed to represent a cstrength recommendation: • cases in which patients refuse surgical biopsy • cases in which suspicious lesions present in cosmetically sensitive areas • cases in which patients have undergone numerous biopsies in the past and wish to avoid additional biopsy procedures • scenarios in which patients have a relative contraindication to surgical biopsy • patients with increased risk of infection (e.g. immunosuppressed patients) • patients with heightened risk of poor wound healing consensus-based auc recommendations for the 23-gep test for the 23-gep test, expert consensus was reached on 8 recommendations (table 5). one recommendation received an astrength consensus recommendation based on the existing published evidence: • differentiation of a nevus from melanoma in an adult patient when the morphologic findings are ambiguous by light microscopic parameters three scenarios for the use of the 23gep test received a b-strength recommendation: • cases with pathology suggestive or suspicious for nevoid melanoma vs. benign melanocytic nevus • cases with pathology suggestive or suspicious for atypical spitz tumor vs. spitzoid melanoma • instances in which pathology is suggestive of or suspicious for severely atypical compound melanocytic proliferation vs melanoma on cosmetically sensitive areas four recommendations received a cstrength recommendation: • instances of pathology suggestive or suspicious for melanoma arising from within a severely dysplastic nevus • cases of pathology suggestive or suspicious for benign vs. malignant blue nevus • to differentiate suspicious lesions in low-risk populations skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 291 296 • upon request from the referring dermatologist following an ambiguous pathology report consensus-based auc recommendations for the 31-gep test a total of 14 recommendations were considered for clinical use of the 31-gep test, and expert consensus was reached on each scenario (table 6). one of 14 received an a-strength recommendation: • use of the 31-gep test to aid in the management of patients who are slnbx negative seven of the recommendations received a b-strength recommendation: • integration of 31-gep results into the decision to adjust follow-up frequency • integration of 31-gep results into the decision to order adjunctive imaging studies • integration of 31gep results into management of patients with t1a tumors with breslow depth <0.8 mm and other adverse prognostic factors • integration of 31-gep results into management of patients with t1 or t2 tumors who are sentinel lymph node biopsy (slnbx) eligible • integration of 31-gep results into management of patients with t1b tumors • integration of 31-gep results into management of patients with t2 tumors • integration of 31-gep results into management of patients with a lowrisk category based on traditional ajcc factors six received a c-strength recommendation: • integration of 31-gep results into the assessment of prognosis and management options for patients with t1a tumors with a positive deep margin • integration of 31-gep results into the assessment of prognosis and management options for patients with t1b tumors with a positive deep margin • integration of 31-gep results to for risk-stratification of patients in clinical trials • use of 31-gep results as a criterion for eligibility for a chemotherapy regimen • t4 disease as a contraindication for use of the 31-gep test • melanoma in situ as a contraindication for use of the 31gep test this study is significant because it represents the first set of expert consensusbased auc recommendations developed for the usage of diagnostic and prognostic gene expression profiles in the management of suspicious pigmented/melanocytic lesions and biopsy-proven melanoma. the recommendations offered herein stratify the strength of evidence available for commonly encountered potential indications for the three validated, clia-certified, readily available gep tests currently available for use in the diagnosis and management of malignant melanoma. previous guidelines have either not commented on the use of gep assays48 or have made broad statements concerning diagnostic and prognostic genetic tests without offering any detailed discussion about defined use in discussion skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 291 297 specific clinical situations.12 given that these diagnostic and prognostic gep assays are clinically available and are each already being used in over 10,000 cases per year811, it is critical to provide clinicians with a set of evidence-based criteria to help ensure that these tests are used for clinically indicated situations. it is imperative that practicing clinicians interpreting these consensus-based recommendations understand the underlying methodology, which led to their creation. the expert consensus panel that determined the strength of each recommendation for gep usage understood that not all cases encountered in the clinical setting will align perfectly with these pre-defined scenarios. these recommendations are meant to provide a framework that can be applied to the majority of clinical scenarios and which can be used as a starting point to provoke thoughtful decision making in situations not specifically defined by the evaluated scenarios. this aligns with the original definition of evidence-based medicine, which notes the individual clinician’s responsibility in critically appraising the literature to permit thoughtful case-specific decision making and assist in patient counseling.49 it is also important that clinicians have an appropriate understanding of the meaning of each recommendation grade as defined by the sort taxonomy.16 although an astrength recommendation represents the highest level of support, even a c-strength recommendation (typically based upon disease-oriented evidence, expert opinion or usual practice) does provide appropriate direction for use in specific situations. studies rated as b or c level evidence are generally accepted as appropriate for establishing clinical recommendations when a level evidence is not available. along these lines, the juxtaposition of the dynamic nature of research with the often static nature of auc recommendation statements must be considered when interpreting these findings. it therefore must be understood by clinicians utilizing these recommendations that the body of available evidence is not static and is constantly evolving. often, governmental bodies and large agencies lag in recognizing the value of new technologies because of lengthy review processes and delays in academic publishing. this study attempted to mitigate these complications by providing the most up-to-date body of evidence, including articles published even a week before the consensus panel was convened. in such a rapidly evolving field, the impetus for this panel was to make recommendations that will affect current dermatologist management. however, the expert consensus panel that developed these recommendations understands and is optimistic that research in this field will continue to evolve. it is therefore the hope of the panel that these recommendations will be updated as new evidence emerges. there are several limitations to this study. only 3 gep tests were considered because they are the only validated, clia-certified, and widely used tests currently available. other tests may be available in the future that may supersede the efficacy of the current tests. an additional limitation, consistent with most publications focusing on recommendations, is that the panel did not consider costs in the analysis. this would have been difficult as healthcare costs in the united states depend on a variety of factors including market factors and policies inherent to specific insurance plans. however, several studies have been published supporting the cost-effectiveness of these tests,24,50 and more will likely be undertaken in the future. in addition, in skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 291 298 many situations, gep tests are now covered by medicare and other insurance plans, and assistance from industry is often available, capping the associated costs and facilitating the accessibility of these assays to patients in need. these expert consensus-based auc recommendations present an evidencebased framework developed through systematic literature review and expert consensus for applying diagnostic and prognostic gep tests to the management of melanoma patients. clinical judgment should be applied to the use of these recommendations, and decisions regarding the use of gep should be made on an individual, case-by-case basis. additional studies aiming to fill these gaps will refine these findings and will be important in the development of updated consensus recommendations. these expert panel consensus-based auc recommendations have been developed for the purpose of guiding clinical decision making regarding the use of gene expression profiles in the management of malignant melanoma. it should be recognized that these consensus-based recommendations are based on the best available evidence at the time that these recommendations were made, in combination with expert opinion. these recommendations are intended to be fluid and may evolve over time as new gene expression evidence profile tests become available and as new evidence regarding existing assays is published. these recommendations are not all-inclusive and should not be expected to definitively address all possible clinical situations faced by dermatologists and dermatologic surgeons. these recommendations were developed with the intent of aiding clinical decision making, but the final judgment as to the utility of any specific diagnostic or prognostic test in a specific situation must be made by the managing physician while considering all data available. conflict of interest disclosures: brian berman, md phd: castle biosciencesconsultant. roger ceilley, md: castle biosciences-consultant. clay cockerell, md: castle biosciences-consultant, dermtech-consultant, stockholder. laura ferris, md: dermtech-consultant, castle biosciences-investigator whitney a high, md jd meng: castle bioscienceshonoraria, advisory board, myriad-consultant. mark lebwohl, md: castle biosciences-consultant. mark s nestor, md phd: castle biosciencesadvisory board. theodore rosen, md: no relevant conflicts. graham h litchman, do ms: no relevant conflicts giselle prado, md: no relevant conflicts. ryan m svoboda, md ms: no relevant conflicts. darrell s rigel, md ms: castle bioscienceshonoraria, advisory board, investigator, consultant, dermtech-consultant, honoraria, myriad-advisory board. funding: national society for cutaneous medicine (a 501(c)3 non-profit entity) funded the consensus development program. the group has received unrestricted educational grants from related companies involved with these technologies. corresponding author: darrell s. rigel 35 e 35 st, #208 new york, ny 10016 212-684-4542 darrell.rigel@gmail.com conclusion disclaimer mailto:darrell.rigel@gmail.com skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 291 292 299 references: 1. prado g, svoboda rm, rigel ds. what's new in melanoma. dermatologic clinics 2019;37:159-68. 2. siegel rl, miller kd, jemal a. cancer statistics, 2019. ca: a cancer journal for clinicians 2019;69:7-34. 3. nathanson kl. using genetics and genomics strategies to personalize therapy for cancer: focus on melanoma. biochemical pharmacology 2010;80:755-61. 4. hyams dm, cook rw, buzaid ac. identification of risk in cutaneous melanoma patients: prognostic and predictive markers. journal of surgical oncology 2019;119:175-86. 5. clarke le, warf mb, flake dd, 2nd, et al. clinical validation of a gene expression signature that differentiates benign nevi from malignant melanoma. journal of cutaneous pathology 2015;42:244-52. 6. gerami p, yao z, polsky d, et al. development and validation of a noninvasive 2-gene molecular assay for cutaneous melanoma. journal of the american academy of dermatology 2017;76:11420.e2. 7. clarke le, pimentel jd, zalaznick h, wang l, busam kj. gene expression signature as an ancillary method in the diagnosis of desmoplastic melanoma. human pathology 2017;70:113-20. 8. decisiondx-melanoma test overview. http://skinmelanoma.com. accessed april 3, 2019. 9. rivers jk, copley mr, svoboda r, rigel ds. non-invasive gene expression testing to rule out melanoma. skin therapy letter 2018;23:1-4. 10. siegel dm, hornberger j. further consideration of the pigmented lesion assay-reply. jama dermatology 2019. 11. mypath melanoma faqs. https://mypathmelanoma.com/faq/#other. accessed april 8, 2019. 12. swetter sm, tsao h, bichakjian ck, et al. guidelines of care for the management of primary cutaneous melanoma. journal of the american academy of dermatology 2019;80:20850. 13. gerami p, cook rw, russell mc, et al. gene expression profiling for molecular staging of cutaneous melanoma in patients undergoing sentinel lymph node biopsy. journal of the american academy of dermatology 2015;72:7805.e3. 14. gerami p, cook rw, wilkinson j, et al. development of a prognostic genetic signature to predict the metastatic risk associated with cutaneous melanoma. clinical cancer research 2015;21:175-83. 15. ferris lk, farberg as, middlebrook b, et al. identification of high-risk cutaneous melanoma tumors is improved when combining the online american joint committee on cancer individualized melanoma patient outcome prediction tool with a 31-gene expression profilebased classification. journal of the american academy of dermatology 2017;76:818-25.e3. 16. ebell mh, siwek j, weiss bd, et al. strength of recommendation taxonomy (sort): a patientcentered approach to grading evidence in the medical literature. american family physician 2004;69:548-56. 17. hsu c-c, sandford ba. the delphi technique: making sense of consensus. practical assessment, research & evaluation 2007;12:1-8. 18. rossi am, sobanko j, lawrence n, et al. physician-centered outcomes for skin cancer treatment. dermatologic surgery 2019;45:869874. 19. thiboutot dm, dreno b, abanmi a, et al. practical management of acne for clinicians: an international consensus from the global alliance to improve outcomes in acne. journal of the american academy of dermatology 2018;78:s1s23.e1. 20. vidal ci, armbrect ea, andea aa, et al. appropriate use criteria in dermatopathology: initial recommendations from the american society of dermatopathology. journal of the american academy of dermatology 2019;80:189207.e11. 21. ferris lk, gerami p, skelsey mk, et al. realworld performance and utility of a noninvasive gene expression assay to evaluate melanoma risk in pigmented lesions. melanoma research 2018;28:478-82. 22. ferris lk, jansen b, ho j, et al. utility of a noninvasive 2-gene molecular assay for cutaneous melanoma and effect on the decision to biopsy. jama dermatology 2017;153:675-80. 23. ferris lk, moy rl, gerami p, et al. noninvasive analysis of high-risk driver mutations and gene expression profiles in primary cutaneous melanoma. j invest dermatol. 2019; 139(5):1127-1134. 24. hornberger j, siegel dm. economic analysis of a noninvasive molecular pathologic assay for pigmented skin lesions. jama dermatology 2018;154:1025-31. 25. jansen b, hansen d, moy r, hanhan m, yao z. gene expression analysis differentiates melanomas from spitz nevi. journal of drugs in dermatology 2018;17:574-6. skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 291 300 26. lee n, scope a, rabinovitz h. assessing skin cancer using epidermal genetic information retrieved by adhesive patch skin surface sampling. dermatologic clinics 2017;35:521-4. 27. wachsman w, morhenn v, palmer t, et al. noninvasive genomic detection of melanoma. the british journal of dermatology 2011;164:797806. 28. cassarino ds, lewine n, cole d, wade b, gustavsen g. budget impact analysis of a novel gene expression assay for the diagnosis of malignant melanoma. journal of medical economics 2014;17:782-91. 29. clarke le, flake dd, busam k, et al. an independent validation of a gene expression signature to differentiate malignant melanoma from benign melanocytic nevi. cancer 2017;123:617-28. 30. cockerell c, tschen j, billings sd, et al. the influence of a gene-expression signature on the treatment of diagnostically challenging melanocytic lesions. personalized medicine 2017;14:123-30. 31. cockerell cj, tschen j, evans b, et al. the influence of a gene expression signature on the diagnosis and recommended treatment of melanocytic tumors by dermatopathologists. medicine 2016;95:e4887. 32. ko js, matharoo-ball b, billings sd, et al. diagnostic distinction of malignant melanoma and benign nevi by a gene expression signature and correlation to clinical outcomes. cancer epidemiology, biomarkers & prevention : a publication of the american association for cancer research, cosponsored by the american society of preventive oncology 2017;26:110713. 33. leachman sa, mengden koon s, korcheva vb, white kp. assessing genetic expression profiles in melanoma diagnosis. dermatologic clinics 2017;35:537-44. 34. reimann jdr, salim s, velazquez ef, et al. comparison of melanoma gene expression score with histopathology, fluorescence in situ hybridization, and snp array for the classification of melanocytic neoplasms. modern pathology 2018;31:1733-43. 35. warf mb, flake dd, 2nd, adams d, et al. analytical validation of a melanoma diagnostic gene signature using formalin-fixed paraffinembedded melanocytic lesions. biomarkers in medicine 2015;9:407-16. 36. berger ac, davidson rs, poitras jk, et al. clinical impact of a 31-gene expression profile test for cutaneous melanoma in 156 prospectively and consecutively tested patients. current medical research and opinion 2016;32:1599-604. 37. cook rw, middlebrook b, wilkinson j, et al. analytic validity of decisiondx-melanoma, a gene expression profile test for determining metastatic risk in melanoma patients. diagnostic pathology 2018;13:13. 38. dillon ld, gadzia je, davidson rs, et al. prospective, multicenter clinical impact evaluation of a 31-gene expression profile test for management of melanoma patients. skin the journal of cutaneous medicine 2018;2:111-21. 39. farberg as, glazer am, white r, rigel ds. impact of a 31-gene expression profiling test for cutaneous melanoma on dermatologists' clinical management decisions. journal of drugs in dermatology 2017;16:428-31. 40. farberg as, glazer am, winkelmann rr, rigel ds. assessing genetic expression profiles in melanoma prognosis. dermatologic clinics 2017;35:545-50. 41. gastman br, gerami p, kurley sj, cook rw, leachman s, vetto jt. identification of patients at risk of metastasis using a prognostic 31-gene expression profile in subpopulations of melanoma patients with favorable outcomes by standard criteria. journal of the american academy of dermatology 2019;80:149-57.e4. 42. greenhaw bn, zitelli ja, brodland dg. estimation of prognosis in invasive cutaneous melanoma: an independent study of the accuracy of a gene expression profile test. dermatologic surgery 2018;44:1494-500. 43. hsueh ec, debloom jr, lee j, et al. interim analysis of survival in a prospective, multi-center registry cohort of cutaneous melanoma tested with a prognostic 31-gene expression profile test. journal of hematology & oncology 2017;10:152. 44. schuitevoerder d, heath m, cook rw, et al. impact of gene expression profiling on decisionmaking in clinically node negative melanoma patients after surgical staging. journal of drugs in dermatology 2018;17:196-9. 45. sidiropoulos m, obregon r, cooper c, sholl lm, guitart j, gerami p. primary dermal melanoma: a unique subtype of melanoma to be distinguished from cutaneous metastatic melanoma: a clinical, histologic, and gene expression-profiling study. journal of the american academy of dermatology 2014;71:1083-92. 46. svoboda rm, glazer am, farberg as, rigel ds. factors affecting dermatologists' use of a 31gene expression profiling test as an adjunct for predicting metastatic risk in cutaneous melanoma. journal of drugs in dermatology 2018;17:544-7. skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 291 301 47. zager js, gastman br, leachman s, et al. performance of a prognostic 31-gene expression profile in an independent cohort of 523 cutaneous melanoma patients. bmc cancer 2018;18:130. 48. coit dg, thompson ja, algazi a, et al. melanoma, version 2.2016, nccn clinical practice guidelines in oncology. journal of the national comprehensive cancer network 2016;14:450-73. 49. evidence-based medicine. a new approach to teaching the practice of medicine. jama 1992;268:2420-5. 50. vetto jt, hsueh ec, gastman br, et al. guidance of sentinel lymph node biopsy decisions in patients with t1-t2 melanoma using gene expression profiling. future oncology (london, england) 2019. skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 291 302 tables table 1: level of evidence for articles related to 2 gep test. reference level of evidence lee n, scope a, rabinovitz h. assessing skin cancer using epidermal genetic information retrieved by adhesive patch skin surface sampling. dermatol clin. 2017;35(4):521-524. 3 wachsman w, morhenn v, palmer t, et al. noninvasive genomic detection of melanoma. br j dermatol. 2011;164(4):797-806. n/a gerami p, yao z, polsky d, et al. development and validation of a noninvasive 2-gene molecular assay for cutaneous melanoma. j am acad dermatol. 2017;76(1):114-120.e2. 1 jansen b, hansen d, moy r, hanhan m, yao z. gene expression analysis differentiates melanomas from spitz nevi. j drugs dermatol. 2018;17(5):574576. 3 ferris lk, moy rl, gerami p, et al. noninvasive analysis of high-risk driver mutations and gene expression profiles in primary cutaneous melanoma. j invest dermatol. 2019; 139(5):1127-1134. 1 ferris lk, gerami p, skelsey mk, et al. real-world performance and utility of a noninvasive gene expression assay to evaluate melanoma risk in pigmented lesions. melanoma res. 2018; 2 ferris lk, jansen b, ho j, et al. utility of a noninvasive 2-gene molecular assay for cutaneous melanoma and effect on the decision to biopsy. jama dermatol. 2017;153(7):675-680. 2 hornberger j, siegel dm. economic analysis of a noninvasive molecular pathologic assay for pigmented skin lesions. jama dermatol. 2018; 154:1025-31. n/a skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 291 303 table 2: level of evidence for articles related to 23 gep test. reference level of evidence leachman sa, mengden koon s, korcheva vb, white kp. assessing genetic expression profiles in melanoma diagnosis. dermatol clin. 2017;35(4):537544. 3 warf mb, flake dd, adams d, et al. analytical validation of a melanoma diagnostic gene signature using formalin-fixed paraffin-embedded melanocytic lesions. biomark med. 2015;9(5):407-16. 3 clarke le, warf mb, flake dd, et al. clinical validation of a gene expression signature that differentiates benign nevi from malignant melanoma. j cutan pathol. 2015;42(4):244-52. 1 clarke le, flake dd, busam k, et al. an independent validation of a gene expression signature to differentiate malignant melanoma from benign melanocytic nevi. cancer. 2017;123(4):617-628. 1 clarke le, pimentel jd, zalaznick h, wang l, busam kj. gene expression signature as an ancillary method in the diagnosis of desmoplastic melanoma. hum pathol. 2017;70:113-120. 2 ko js, matharoo-ball b, billings sd, et al. diagnostic distinction of malignant melanoma and benign nevi by a gene expression signature and correlation to clinical outcomes. cancer epidemiol biomarkers prev. 2017;26(7):1107-1113. 1 reimann jdr, salim s, velazquez ef, et al. comparison of melanoma gene expression score with histopathology, fluorescence in situ hybridization, and snp array for the classification of melanocytic neoplasms. mod pathol. 2018; 2 cassarino ds, lewine n, cole d, wade b, gustavsen g. budget impact analysis of a novel gene expression assay for the diagnosis of malignant melanoma. j med econ. 2014;17(11):782-91. n/a cockerell cj, tschen j, evans b, et al. the influence of a gene expression signature on the diagnosis and recommended treatment of melanocytic tumors by dermatopathologists. medicine (baltimore). 2016;95(40):e4887. 2 cockerell c, tschen j, billings sd, et al. the influence of a gene-expression signature on the treatment of diagnostically challenging melanocytic lesions. per med. 2017;14(2):123-130. 2 skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 291 304 table 3: level of evidence for articles related to 31 gep test. reference level of evidence farberg as, glazer am, winkelmann rr, rigel ds. assessing genetic expression profiles in melanoma prognosis. dermatol clin. 2017;35(4):545550. 3 sidiropoulos m, obregon r, cooper c, sholl lm, guitart j, gerami p. primary dermal melanoma: a unique subtype of melanoma to be distinguished from cutaneous metastatic melanoma: a clinical, histologic, and gene expressionprofiling study. j am acad dermatol. 2014;71(6):1083-92. 2 gerami p, cook rw, russell mc, et al. gene expression profiling for molecular staging of cutaneous melanoma in patients undergoing sentinel lymph node biopsy. j am acad dermatol. 2015;72(5):780-5.e3. 1 gerami p, cook rw, wilkinson j, et al. development of a prognostic genetic signature to predict the metastatic risk associated with cutaneous melanoma. clin cancer res. 2015;21(1):175-83. 2 ferris lk, farberg as, middlebrook b, et al. identification of high-risk cutaneous melanoma tumors is improved when combining the online american joint committee on cancer individualized melanoma patient outcome prediction tool with a 31-gene expression profile-based classification. j am acad dermatol. 2017;76(5):818-825.e3. 2 hsueh ec, debloom jr, lee j, et al. interim analysis of survival in a prospective, multi-center registry cohort of cutaneous melanoma tested with a prognostic 31-gene expression profile test. j hematol oncol. 2017;10(1):152. 1 cook rw, middlebrook b, wilkinson j, et al. analytic validity of decisiondxmelanoma, a gene expression profile test for determining metastatic risk in melanoma patients. diagn pathol. 2018;13(1):13. 3 greenhaw bn, zitelli ja, brodland dg. estimation of prognosis in invasive cutaneous melanoma: an independent study of the accuracy of a gene expression profile test. dermatol surg. 2018; 2 zager js, gastman br, leachman s, et al. performance of a prognostic 31gene expression profile in an independent cohort of 523 cutaneous melanoma patients. bmc cancer. 2018;18(1):130. 2 gastman br, gerami p, kurley sj, et al. identification of patients at risk for metastasis using a prognostic 31-gene expression profile 3 in subpopulations of melanoma patients with favorable outcomes by standard criteria. j am acad dermatol. j am acad dermatol. 2019 jan;80(1):149-157. 2 berger ac, davidson rs, poitras jk, et al. clinical impact of a 31-gene expression profile test for cutaneous melanoma in 156 prospectively and consecutively tested patients. curr med res opin. 2016;32(9):1599-604. 2 farberg as, glazer am, white r, rigel ds. impact of a 31-gene expression profiling test for cutaneous melanoma on dermatologists' clinical management decisions. j drugs dermatol. 2017;16(5):428-431. n/a dillon ld, gadzia je, davidson rs, et al. prospective, multicenter clinical impact evaluation of a 31-gene expression profile test for management of melanoma patients. skin. 2018;2(2). 2 schuitevoerder d, heath m, cook rw, et al. impact of gene expression profiling on decision-making in clinically node negative melanoma patients after surgical staging. j drugs dermatol. 2018;17(2):196-199. 2 svoboda rm, glazer am, farberg as, rigel ds. factors affecting dermatologists' use of a 31-gene expression profiling test as an adjunct for predicting metastatic risk in cutaneous melanoma. j drugs dermatol. 2018;17(5):544-547. 3 skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 291 305 table 4: consensus-based recommendations for utilization of the 2 gep test. recommendation strengtha patients that refuse surgical biopsy c lesions present in cosmetically sensitive areas c patients with relative contraindications to surgical biopsy such as anticoagulation or anesthetic sensitivity c patients with wound healing risk (e.g. excessive or hypertrophic scarring or prolonged healing) c patients with increased infection risk (immunosuppressed patients) c patients with atypical lesions requiring assessment beyond visual inspection to help in selection for biopsy b patients who have undergone numerous biopsies in the past who don’t want additional biopsies c abased on sort taxonomy, a = consistent, good-quality patient-oriented evidence, b = inconsistent or limitedquality patient-oriented evidence, c = consensus, disease-oriented evidence, usual practice, expert opinion, or case series table 5: consensus-based recommendations for utilization of the 23 gep test. recommendation strengtha differentiation of a nevus from melanoma in an adult patient when the morphologic findings are ambiguous by light microscopic parameters a pathology suggestive or suspicious for nevoid melanoma vs. benign melanocytic nevus b pathology suggestive or suspicious for melanoma arising within a severely dysplastic nevus c pathology suggestive or suspicious for malignant blue nevus vs. benign blue nevus c pathology suggestive or suspicious for atypical spitz tumor vs. spitzoid melanoma b pathology suggestive or suspicious for severely atypical compound melanocytic proliferation vs melanoma on cosmetically sensitive areas and special sites, including digits, acral, genital, ears and scalp b differentiate suspicious lesions in low risk populations c for the dermatologist to request after ambiguous pathology report c abased on sort taxonomy, a = consistent, good-quality patient-oriented evidence, b = inconsistent or limitedquality patient-oriented evidence, c = consensus, disease-oriented evidence, usual practice, expert opinion, or case series skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 291 306 table 6: consensus-based recommendations for utilization of the 31 gep test. recommendation strengtha integrating 31gep results into assessing prognosis and management options for patients with: t1a tumors in whom there is significant uncertainty about the adequacy of microstaging (positive deep margin) c t1b+ tumors in whom there is significant uncertainty about the adequacy of microstaging (positive deep margin) c integrating 31 gep results into the decision: to adjust follow up regimens b to assess need for imaging b integrating 31gep results into managing patients: with t1a tumors with breslow depth <0.8 mm and with other adverse features (eg. very high mitotic index [≥2/mm2], lymphovascular invasion, or a combination of these factors) b with t1 and t2 cutaneous melanoma who are sentinel lymph node biopsy (slnbx) eligible b with t1b tumors (≥ 0.8 mm or < 0.8 mm with ulceration) b with t2 tumors b integrating 31gep results into subsequent management of patients: who are sentinel node negative a who are in ajcc “low risk” categories: (thin (<1mm), stage i-iia, slnbx-) b integrating 31gep results into randomizing patients in clinical trials for risk stratification (randomization) c integrating 31gep results as a criteria for inclusion in a chemotherapy regimen c contraindications: do not perform 31gep in patients with t4 disease c do not perform in patients with melanoma in situ c abased on sort taxonomy, a = consistent, good-quality patient-oriented evidence, b = inconsistent or limitedquality patient-oriented evidence, c = consensus, disease-oriented evidence, usual practice, expert opinion, or case series skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 507 research letter support group utilization and perspectives among hidradenitis suppurativa patients devea r. de, bs1, terri shih, bs2, swetha atluri, ba3, denise fixsen4, brindley brooks4, jennifer l. hsiao, md5, vivian y. shi, md6 1 university at buffalo, jacobs school of medicine and biomedical sciences, buffalo, ny 2 david geffen school of medicine, university of california, los angeles, ca 3 university of arizona college of medicine, tucson, az 4 hs connect, puyallup, wa 5 university of southern california, department of dermatology, los angeles, ca 6 university of arkansas for medical sciences, department of dermatology, little rock, ar abstract introduction: hidradenitis suppurativa (hs) is a chronic inflammatory dermatosis associated with significant psychosocial burden. hs patients are more likely to experience mental health comorbidities such as depression and anxiety. they may also experience isolation due to fear of stigmatization as hs lesions are often associated with pain, scarring, and odor. this study investigates the perspectives of hs patients on hs support groups and the usage of this resource among this population. methods: an anonymous redcap survey was utilized via online social media hs support groups between 10/2021-1/2022 to collect demographic, usage, and perspective data. comparative statistics were conducted and p-value of <0.05 was considered significant. results: of the 166 respondents, 78% respondents were part of an hs support group however, only 12% of respondents were recommended to join by their main hs healthcare provider and most (68%) learned about support groups through their own internet searches. most respondents were daily (42%) and weekly (38%) support group users. virtual meetings were preferred by the majority compared to in person meetings (50% vs 13%). the top reasons respondents reported attending support groups were to better understand hs, increasing their knowledge of hs resources, and access to treatment/care tips. respondents without dermatologists as their main hcp and skin of color (soc) respondents were more likely to report that support groups improved their care of hs (4.29 vs 3.90, p=0.031). conclusion: our findings highlight the preferential format of virtual support groups and that support groups may be an underutilized resource by healthcare providers for their patients. support groups may help to narrow gaps in education when patients are unable to access or have delays in obtaining dermatological care, especially in soc patients who have historically experienced higher rates of healthcare disparities. skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 508 hidradenitis suppurativa (hs) is a chronic inflammatory dermatosis with significant physical, social, and emotional burden.1 hs patients may have higher odds of having depression and anxiety.2 they may also experience isolation due to fear of stigmatization with pain, scaring, and odor.3,4 hs support groups serve as a resource to support mental health for hs patients. learning about specific preferences from patients may help tailor support group recommendations. herein, we aim to learn about hs patient support group use and perspectives. an anonymous redcap survey was distributed through online social media hs support groups between 10/2021-1/2022. data regarding demographics, use, and perspectives of hs support groups was collected. comparative statistics were completed and differences in perspectives were analyzed based on the respondent’s age, gender, race, hs severity, and the type of healthcare provider (hcp) they see for hs. a p-value of <0.05 was considered significant. the majority of the 196 respondents were female (92%, 180/196) and white (75%, 147/196). a dermatologist was the primary hcp for hs in 65% (128/196) of patients. 12% (23/196) were seen at an hs specialty clinic. out of 166 respondents, 78.3% (130/166) were in a hs support group and 73.8% had joined for 2 years or less (96/130). only 12% (20/166) were recommended to join a support group by their main hcp, with most respondents learning about support groups through internet searches (68.7%, 114/166). most respondents utilized their support groups daily (41.5%, 54/130) and weekly (37.7%, 49/130). most respondents preferred virtual meetings over in person meetings (50%, 81/162 vs 13%, 21/162). (figure 1) the top three reasons that respondents reported going to a support group were to better understand hs (79%, 130/164), learn about available resources (79%, 130/164), and gain access to treatment and care tips (77%, 127/164) (figure 2). close to half of respondents reported a difference between the information they receive from hcps vs support group regarding hs causes (46%, 75/162) and hs treatments (52%, 84/162). compared to respondents with dermatologists as their main hs hcp, those without were more likely to report support groups improve their care of hs (4.24 vs 3.86, p=0.049) and noted a difference in information about hs causes (3.89 vs 3.24, p=0.005) that they receive from their hcp vs support groups. skin of color (soc) respondents were significantly more likely to agree that support groups improve their care of hs (4.29 vs 3.90, p=0.031) and increases their knowledge of available hs resources (4.68 vs 4.37, p=0.02) vs non-soc respondents. our results highlight the positive impact that hs support groups have in hs education. with increasing awareness of hs, support group use has increased over the past two years. virtual support groups may be the preferred format due to scheduling flexibility, ease of attendance, and physical comfort. introduction methods results discussion skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 509 figure 1. respondent reported perspectives and outcomes on hs support groups skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 510 most respondents trust the information provided in support groups, but also find differences in information provided by their hcp’s and support group. respondents without dermatologists and soc respondents were more likely to report that support groups improved their care of hs. historically, soc patients have experienced healthcare disparities and may lack access to specialist care for hs. thus, support groups may narrow gaps in education when patients are unable to access or have delays in obtaining dermatological care.5 the results show hcp’s may be underutilizing hs support groups as a recommended resource. hcp’s can recommend support groups to address emotional health in addition to other mental health referrals. study limitations include self-reported hs disease severity and female-predominant responses, limiting generalizability. ultimately hcp’s, support groups, and researchers should work alongside each other to continue advocacy efforts, raise awareness about hs, and reduce gaps in care. acknowledgements: an anonymous survey was distributed with permission through online social media hs support groups between october 2021 to january 2022. we are grateful to the members of hs support groups for their participation, including hs connect, hope for hs, and hidradenitis suppurativa warriors. conflict of interest disclosures: vys is on the board of directors for the hidradenitis suppurativa foundation (hsf), is a stock shareholder of learn health and has served as an advisory board member, investigator, speaker, and/or received research funding from sanofi genzyme, regeneron, abbvie, eli lilly, novartis, sun pharma, leo pharma, pfizer, incyte, boehringer-ingelheim, aristea therapeutics, menlo therapeutics, dermira, burt’s bees, galderma, kiniksa, ucb, targetpharmasolutions, altus lab, myor, polyfin, alumis, gpskin and skin actives scientific. jlh is on the board of directors for the hidradenitis suppurativa foundation, and has served as an advisor for novartis, ucb, and boehringer ingelheim and as a speaker and advisor for abbvie. funding: none corresponding author: vivian y. shi, md department of dermatology university of arkansas for medical sciences 4301 w. markham st., #576 little rock, ar 72205 phone: (501) 526-6994 e-mail: vivian.shi.publications@gmail.com references: 1. gooderham m, papp k. the psychosocial impact of hidradenitis suppurativa. j am acad dermatol. 2015 nov;73(5 suppl 1):s1922. 2. patel kr, lee hh, rastogi s, vakharia pp, hua t, chhiba k, et al. association between hidradenitis suppurativa, depression, anxiety, and suicidality: a systematic review and meta-analysis. j am acad dermatol. 2020 sep;83(3):737–44. 3. de dr, rick jw, shih t, alavi a, hsiao jl, shi vy. lifestyle modifications and complementary treatments for hidradenitis suppurativa. dermatological reviews. 2022 jan 28;der2.117. 4. esmann s, jemec gbe. psychosocial impact of hidradenitis suppurativa: a qualitative study. acta derm venereol. 2011 may;91(3):328–32. 5. rick jw, thompson am, fernandez jm, maarouf m, seivright jr, hsiao jl, et al. misdiagnoses and barriers to care in hidradenitis suppurativa: a patient survey. australas j dermatol. 2021 nov;62(4):e592– 4. mailto:vivian.shi.publications@gmail.com mailto:vivian.shi.publications@gmail.com skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 891 brief article recalcitrant grover’s disease successfully managed with dupilumab and naltrexone in a middle-aged woman: a case study kaylin beiter, phd1, christy behnam, md2, bridget e. shields, md2 1 louisiana state university health sciences center new orleans school of medicine, new orleans, la 2 university of wisconsin hospital and clinics, department of dermatology, madison, wi grover’s disease, also known as transient acantholytic dermatosis, is an acquired dermatologic condition characterized by a pruritic, erythematous, and scaly papulovesicular eruption affecting the trunk. the cause remains unknown, though condition worsening has been associated with heat, sweat, renal failure, and malignancy.1 the diagnosis is primarily clinical, though biopsy can be helpful in atypical cases. grover’s disease is relatively uncommon, and prevalence is primarily limited to older adults. to date only a few empiric epidemiologic studies have been performed. one of these, a 30-month retrospective assessment of 3,750 patients with dermatologic consultations during their hospitalization, showed the prevalence of grover’s disease was 0.8% with a male: female ratio of 1.8.2 a second study with abstract introduction: grover’s disease, or transient acantholytic dermatosis, is a common benign papulovesicular disorder that often affects elderly men. it is typically managed with topical therapeutics in this population. we present here an uncommon case of grover’s disease, occurring in a relatively younger patient, that was recalcitrant to typical therapeutics modalities. case report: a 45-year-old woman presented to our clinic with a several month history of discrete, pink, ill-defined pruritic papules on her torso with sparing of her extremities. grover’s disease was diagnosed based on her clinical presentation and subsequently biopsy confirmed. she failed multiple topical medications, oral acitretin, and only experience minimal relief when transitioned to naltrexone. dupilumab was added to her regimen, with rapid improvement. she was eventually transitioned down to dupilumab monotherapy and has remained clear since. conclusion grover’s disease is not common among middle-aged women. novel therapies, such as biologics, have been efficacious in elderly (especially male) populations with this condition. our case demonstrates the importance of attempting new treatment modalities such as dupilumab for patients with recalcitrant disease. novel application of these biologic treatments may be needed in particular for atypical cases, such as when patients do not fit the known epidemiologic profile. introduction skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 892 outpatient data from the united states largely recapitulated both the prevalence and gender ratio.3 in both, the average patient with grover’s disease was older than 64 years. there is presently no standard of care for grover’s disease, though most patients are started on topical steroids, calcineurin inhibitors, retinoids, or antibiotics. dupilumab has recently been used to treat the intense pruritus associated with grover’s disease. the theoretical mechanism supporting the use of dupilumab in grover’s disease is welldescribed, and is thought to target pruritoceptive pathways.5 however, reports of treatment with dupilumab are few, and have been largely limited to assessment in male, elderly patients. we present here a middle-aged woman with refractory grover’s disease who eventually responded to treatment with dupilumab. a 45-year-old woman presented to our clinic with a several month history of discrete, pink, ill-defined papules on her torso with sparing of her extremities (figure 1). the lesions had an insidious onset, were intermittently pruritic, and were exacerbated with sweating and heat. the patient had been following a gentle skin care regimen with intermittent trials of topicals including 1% hydrocortisone cream, baby power and miconazole powder without significant improvement. she denied any personal or family history of similar skin lesions or any other dermatologic conditions. upon clinical evaluation, grover’s disease was suspected. consistent topical use of triamcinolone 0.1% ointment over 2-3 weeks was recommended in addition to 25mg oral diphenhydramine twice daily. when this regimen only provided partial relief, topical steroids were escalated to using topical clobetasol 0.05% cream daily for two weeks. the lesions initially resolved on this regimen but eventually recurred within the subsequent three months, prompting a skin biopsy to confirm the diagnosis. on histology, focal acantholysis and dyskeratosis were observed, consistent with the suspected grover’s disease. after confirming the diagnosis, the patient was started on topical calcipotriene 0.005% cream daily for a month. after which, topical 0.1% triamcinolone cream daily was added to the calcipotriene regiment. due to lack of significant improvement after three months, the patient was initiated on 10 mg daily oral acitretin for three months, which was then increased to 17.5mg daily for three months, and later escalated to 25mg daily. after two weeks on 25mg of acitretin, the patient experienced dermatitis and hair loss. her acitretin dose was subsequently lowered back to 17.5 mg daily. the patient was also started on a naltrexone 1.5 mg daily with escalation to 4.5mg daily. after two months on the 17.5mg daily dose of acitretin and 4.5mg daily dose of naltrexone, the patient continued to experience worsening hair loss. acitretin was discontinued. after multiple first and second line therapies failed to manage the condition, alternative novel management approaches were discussed, and dupilumab (dupixent) 300mg every-other-week sq were started. the patient was continued on the naltrexone as well and noticed a major improvement in her condition within a few weeks. after two months on the dupilumab, naltrexone was discontinued. the patient initially experienced rebound pruritus for two weeks upon discontinuation of the naltrexone, however this pruritus progressively resolved. six months after starting dupilumab she remained completely clear of new skin lesions and reported no pruritus (figure 2). case report skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 893 figure 1. before treatment, anterior view. figure 2. after treatment, anterior and posterior view. skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 894 the successful management of grover’s disease with dupilumab, a monoclonal antibody that binds to interleukin-4 (il-4) receptors, has only been reported in a few instances. existing cases are amongst men above the age of 70, with only a single case reported of a woman in her 50s.5–8 there is theoretical support for use of dupilumab among post-menopausal women along with elderly men, given that women older than the age of 50 develop an increased proportion of t-helper 1 lymphocytes (th1 cells) and proinflammatory cytokine secretion.9,10 this known increased th1 immunologic profile has been hypothesized as the mechanism by which dupilumab may be efficacious in postmenopausal women, as previously reported.5 therefore, we questioned the potential efficacy in a pre-menopausal woman nearly 20 years younger than the average age of reported success with dupilumab. however, the decision to start this biologic was made due to her failure to respond completely to other therapies. fortunately, her condition was greatly improved with dupilumab and eventually stabilized on monotherapy. given the significant improvements seen in our patient’s condition, this case serves to support the wider clinical use of dupilumab in younger females. in addition, this case suggests that the pruritus and dermatologic manifestations of grover’s disease may be mediated by il-4, regardless of patient age or hormonal status. this il-4 based mechanism is implicated in the pruritoceptive pathway.5 however, improved pruritus observed in our case with the additional use of naltrexone also suggests that neuropathic pruritus may be implicated as well in grover’s disease pathophysiology. the combination of dupilumab with naltrexone was extremely successful in reliving pruritus. naltrexone has not been widely studied for use in grover’s disease specifically, though the anti-pruritic effects have been discussed in both theoretical and practical studies of older adults.11,12 our case highlights dupilumab and naltrexone to successfully manage grover’s disease in a pre-menopausal woman. our case demonstrates the importance of early consideration of dupilumab for immunologic targeting of pruritoceptive itch pathways in grover’s disease. in addition, we report on the potential use of naltrexone as a bridge therapy to temporarily target neuropathic itch. clinicians should thoughtfully investigate pruritus in younger women and maintain a high index of suspicion for grover’s disease. conflict of interest disclosures: none funding: none corresponding author: kaylin beiter, phd 2020 gravier street, floor 7 new orleans, la 70112 email: kbeite@lsuhsc.edu references: 1. aldana pc, khachemoune a. grover disease: review of subtypes with a focus on management options. int j dermatol. 2020;59(5):543-550. doi:10.1111/ijd.14700 2. french le, piletta pa, etienne a, salomon d, saurat jh. incidence of transient acantholytic dermatosis (grover’s disease) in a hospital setting. dermatology1. 1999;198(4):410-411. 3. scheinfeld n, mones j. seasonal variation of transient acantholytic dyskeratosis (grover’s disease). j am acad dermatol. 2006;55(2):263-268. doi:10.1016/j.jaad.2006.01.029 4. bellinato f, maurelli m, gisondi p, girolomoni g. clinical features and treatments of transient acantholytic discussion conclusion skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 895 dermatosis (grover’s disease): a systematic review. j ger soc dermatology. 2020;18(8):826-833. doi:10.1111/ddg.14202 5. butler dc, kollhoff a, berger t. treatment of grover disease with dupilumab. jama dermatology. 2021;157(3):353-356. doi:10.1001/jamadermatol.2020.5097 6. barei f, torretta s, morini n, ferrucci s. a case of grover disease treated with dupilumab: just serendipity or a future perspective? dermatol ther. 2022;35(5):e15429. doi:10.1111/dth.15429 7. brummer gc, wang lt, sontheimer rd. a possible role for dupilumab (dupixent) in the management of idiopathic chronic eczematous eruption of aging. dermatol online j. 2018;24(2):13030/qt55z1f6xh. 8. shelton e, doolittle c, shinohara mm, thompson ja, moshiri as. can’t handle the itch? refractory immunotherapy-related transient acantholytic dermatosis: prompt resolution with dupilumab. jaad case reports. 2022;22:31-33. doi:10.1016/j.jdcr.2022.01.029 9. valiathan r, ashman m, asthana d. effects of ageing on the immune system: infants to elderly. scandanavian j immunol. 2016;83(4):255-266. doi:10.1111/sji.12413 10. han a, kim jy, kwak-kim j, lee sk. menopause is an inflection point of agerelated immune changes in women. joural reprod immunol. 2021;146:103346. doi:10.1016/j.jri.2021.103346 11. lee b, elston dm. the uses of naltrexone in dermatologic conditions. j am acad dermatol. 2019;80(6):1746-1752. doi:10.1016/j.jaad.2018.12.031 12. lee j, shin ju, noh s, park co, lee kh. clinical efficacy and safety of naltrexone combination therapy in older patients with severe pruritus. ann dermatol. 2016;28(2):159-163. doi:10.5021/ad.2016.28.2.159 powerpoint presentation clinical use of the 31-gene expression profile for informing sentinel lymph node biopsies: a prospective, multicenter study background ›a positive sentinel lymph node (sln) is an indicator of poor outcomes in cutaneous melanoma (cm); however, using clinicopathologic factors to select patients results in up to 88% of all patients having a negative slnb.1 ›sln biopsies (slnbs) cost up to $15,223 and are associated with complications in 11.3% of cases.2-3 in order to have a positive impact on survival, 142 slnbs are needed to find one patient who will die from their disease.4 ›the 31-gene expression profile (gep) test stratifies patient risk for recurrence, metastasis, and melanoma death as class 1a (low-risk), class 1b/2a (intermediate risk), and class 2b (high-risk). ›the 31-gep is validated to identify patients who have <5% risk of positive slnb and good outcomes, indicating that these patients could safely forego the procedure.5-6 acknowledgments & disclosures references ›cnb, ka, cj, bm, and sjk are employees and shareholders/option holders of castle biosciences, inc. ›jmg is on the speakers bureau at castle biosciences. my has no conflicts to disclose. results presented at the winter clinical 2023 conferences. j. michael guenther, md1, christine n. bailey, mph2, kelli ahmed, phd2, clare johnson, rn2, brian martin, phd2, sarah j. kurley, phd2, maki yamamoto, md3 1st. elizabeth physicians, edgewood, ky, usa, 2castle biosciences, friendswood, tx, usa, 3university of california-irvine, orange, ca, usa ›the 31-gep result and patient preference play a significant role in slnb decisions. ›85% of slnb decisions were influenced by the 31-gep result. 83% of slnb decisions that were discordant with 31-gep results were due to patient preference. ›using the 31-gep class 1a result in conjunction with current guidelines resulted in a 29% decrease in slnbs compared to not using the 31-gep to help guide slnb decisions. conclusions ›prospectively enrolled patients (n=191) with t1a tumors and at least one high-risk feature, t1b, or t2 tumors were seen by surgical oncologists (89.1%), dermatologists (7.8%), and medical oncologists (3.1%) from 22 centers. ›clinicians received 31-gep results prior to slnb decisions and were asked which features influenced their decision whether to perform an slnb. if the procedure was performed, outcomes were recorded at a subsequent visit. ›to test the impact of the 31-gep on slnb rates, in-study procedure rates were compared to varying baseline rates using the exact binomial test.6 ›the association between clinicopathological features with slnb performance was studied using stepwise selection on a logistic regression model descriptor class 1a (n=138) class 1b (n=23) class 2a (n=13) class 2b (n=19) all pts (n=193) p-value age, median (range) 65 (25-87) 70 (39-90) 65 (22-84) 69 (50-88) 65 (22-90) 0.118 breslow thickness, median (range) 0.9 (0.2-1.9) 0.8 (0.6-1.85) 1.5 (0.9-1.9) 1.1 (0.4-2) 0.9 (0.2-2) <0.001 ulceration <0.001 absent 132 (95.7%) 20 (87.0%) 7 (53.9%) 9 (47.4%) 168 (87.1%) present 4 (2.9%) 2 (8.7%) 6 (46.2%) 10 (52.6%) 22 (11.4%) unknown 2 (1.5%) 1 (4.4%) 0 (0%) 0 (0%) 3 (1.6%) mitotic rate (1/mm2) 0.003 <2 99 (78.0%) 14 (63.6%) 4 (33.3%) 10 (55.6%) 127 (70.9%) ≥2 28 (22.1%) 8 (36.4%) 8 (66.7%) 8 (44.4%) 52 (29.1%) physician specialty 0.037 surgical oncologist 125 (90.6%) 17 (73.9%) 13 (100%) 17 (89.5%) 172 (89.1%) dermatologist 10 (7.3%) 5 (21.7%) 0 (0%) 0 (0%) 15 (7.8%) medical oncologist 3 (2.2%) 1 (4.4%) 0 (0%) 2 (10.5%) 6 (3.1%) figure 1. physicians use 31-gep results to guide and implement decisions about slnbs in a risk-aligned manner methods 1. huang, h., et al. front oncol 12, 817510 (2022). 2. agnese et al. surgery (2003) 3. moody et al. ejso 2017. 4.marchetti et al. jama derm (2021). 5. vetto, j. t. et al. future oncology 15, 1207–1217 (2019). 6. whitman, e.d., et al. jco-po 5, 1466-79 (2021). the 31-gep result influenced 85% of slnb decisions. when the 31-gep result influenced for slnb, 92% were performed, and when the 31-gep result influenced against slnb, 70% were not performed, indicating that the 31-gep is used to guide clinical actions. of the slnb decisions that were discordant with the 31-gep result, 83.0% (29/35) were due to patient preference. table 1. demographic data (n=193) ›most patients have a negative slnb ›identifying patients at low risk of having a positive slnb can: ›reduce the number of unnecessary slnbs ›reduce slnb-associated complications ›reduce healthcare costs clinical implications decision factor odds ratio (95% ci) 31-gep 14.8 (6.1-46.8)* patient preference 32.7 (11.5-126.5)* tumor-infiltrating lymphocytes 4.7 (1.1-22.5) breslow thickness 2.6 (1.2-6.2) age 2.1 (0.9-5.1) stepwise selection on logistic regression model to identify factors associated with performing an slnb. *pvalues <0.01; other variables, while contributing to the model, did not reach the statistical significance mark of <0.01 used in this analysis. figure 2. slnb performance rates are significantly reduced when incorporating the 31-gep result into decision-making using the 31-gep in conjunction with current guidelines reduced the number of slnbs in the entire population relative to the baseline control (59.1% vs. 78.0%). in class 1a patients, the reduction in slnb performance was 29.4%. ** p<0.01 results 31-gep class 1a 1b/2a 2b total 85% influenced by 31-gep slnb performed (concordant with 31-gep influence) slnb not performed slnb not performed (concordant with 31-gep influence) slnb performed70% 92% -29% -19% 49% 3% 59% 9% 78% 10% slnb performance reduction rate, relative to contemporary cohort slnb positivity rate slnb performance rate p e rc e n t, % 0 20 40 60 80 100 -20 -40 ** ** class 1a (low risk), n=138 all pts, n=193 contemporary comparison cohort, n=856 study design patients with cm considering slnb physician and patient make decision about slnb after receiving 31-gep results slnb no slnb follow for outcomes table 2. factors associated with decision to perform or forego slnb. 31-gep testing forego slnb perform slnb no influence on slnb in fl u e n c e o f 3 1 -g e p o n s l n b d e c is io n ( n u m b e r o f d e c is io n s ) scan or click here for more info https://castlebiosciences.com/research-development/publications/ e-poster la roche posay vf-vd primary and secondary prevention of skin cancer vary considerably f rom one country to another. this survey investigates knowledge and behaviors regarding sun exposure in europe compared to other continents such as north and south america, af rica, oceania and asia. this european survey among germany, france, spain, italy, united kingdom and russia (n= 6,000) was conducted online f rom 28 september-18 october 2021 and was part of a broader worldwide survey (n=17,001) conducted in 17 countries (5 continents). automated selection f rom the ipsos online panel ensured samples of 1,000 individuals in each country fit the quotas method based on gender, age, employment status, and country regions. data covered demographics, phototype, exposure habits and practices, knowledge and understanding of risks. “at-risk” sub-population was defined as individuals with a history of melanoma/non melanoma skin cancer, pre-cancerous lesions, photodermatosis, or currently on photosensitive or immunosuppressive drugs. t. passeron1, b. dreno2, s. puig3, c.l. goh4, h.y. kang5, f. ly6, a. morita7, j. ocampo candiani8, s. schalka9, l. wei10, a.l. demessant11, c. le floc’h11, d. kerob11, h.w. lim12, j. krutmann13 1department of dermatology, côte d’azur university, nice university hospital center, inserm u1065, c3m, nice, france. 2department of dermato-oncology, cic 1413, crcina, nantes university hospital center, nantes, france. 3melanoma unit, dermatology department, barcelona university hospital clinic, barcelona, spain. 4national skin centre, singapore. 5department of dermatology, ajou university school of medicine, suwon, south korea. 6department of dermatology, cheikh anta diop dakar university, eps institute of social hygiene, dakar, senegal. 7department of geriatric and environmental dermatology, nagoya city university graduate school of medical sciences, nagoya, japan. 8department of dermatology, medical faculty university hospital of nuevo leon, monterrey, mexico. 9medcin skin research center and biochemistry department, chemistry institute of sao paulo university, sao paulo, brazil. 10department of dermatology, the general hospital of air force pla, beijing, china. 11la roche posay laboratoire dermatologique, levallois, france. 12department of dermatology, henry ford health system, detroit, mi, usa. 13iuf leibniz research institute for environmental medicine, dusseldorf, germany medical faculty, heine-university, dusseldorf, germany sun exposure and associated risks in 17 countries: results from europe compared to other continents introduction : methods : europeans are more likely to perceive the benefits of the sun and tanning appeal. sun-protection practice appears more inadequate in europe compared to other continents. this survey provides insight into the need for additional photoprotection education. survey conducted by ipsos, sponsored by laboratoire dermatologique la roche posay conclusion : the european population comprised 48% men, average age was 47.5 years (sd:15.8) and 54% were of phototype 1-2. non-europeans countries in comparison were less represented in phototype 1-2 (43%). 82% of europeans stated that a tanned skin looks attractive vs 67% outside of europe. and 73% of europeans indicated that a tan makes a healthy look, a different perception in non-eu countries (59%). however, 92% of europeans were aware of sun-related skin-health issues, a lower awareness out of europe (86%). similarly, europeans were more aware of the skin aging risk (86%) vs non-eu countries (79%). but only 56% of europeans did know that sun protection is useful when the weather is overcast, a lower knowledge vs non-eu countries (64%). moreover, 24% of europeans indicated it was safe to go out without protection when already tanned vs 21% outside of europe. in terms of photoprotection, 16% of europeans said they protected all year round, vs 27% out of europe. only 10% of europeans systematically/often use all protections measures during exposure vs 14% out of europe. in detail, europeans were less likely to systematically/often wear a hat/cap (51% in europe vs 57% out of europe), wear protective clothes (33% vs 51%) or stay in the shade (73% vs 80%). on the other hand, europeans were more likely to systematically/often put sunscreen especially on arms, legs and chest (62%) compared to non-europeans (52%). more generally, 10% of europeans said they never used sunscreen compared to 16% outside of europe. during sun exposure, among those who applied sunscreen, 34% of europeans applied only once a day, this low f requency habit reached 49% out of europe. 47% of europeans regretted not having previously used better protection in the past, vs 63% out of europe. in terms of knowledge, 74% of europeans did not understand the difference between uva and uvb vs 69% out of europe. at-risk europeans individuals (11%, n=655) had better knowledge and photoprotection habits than the overall european population; but only 21% systematically/often used all the protection measures during sun exposure and still 58% felt they did not understand the difference between uva and uvb. results : 35% yes, absolutely no, not at allyes, somewhat no, not really i don’t know very well not at allfairly well not very well i don’t know yes, absolutely no, not at allyes, somewhat no, not really i don’t know europe regrets of not having better protected themselves from the sun in the past 15% knowledge of the difference between uva and uvb 15% 12% 3% 30% 21% 42% 5%11% 21% 40% not well/dk 58% not well/dk 74% how tanning is perceived a tanned skin looks attractive the sun gives you energy a tan makes a person look healthy you cannot imaginecoming back f rom holidays without being tanned the usefulness of sun protection photoprotection habits i seek to tan with a sun protection yes, all year round, whatever the season yes, but only on hot and sunny days, whether you are on holiday or not yes, but only when you are on holiday (at the beach, when skiing, etc.) no, not really frequency of sunscreen application once a day twice a day every two hours sunscreen with a very high sun protection factor (spf) of 50+ is dedicated to people who are particularly at risk it is safe to go out in the sun without protection if you are already tanned 37% 84% of people don’t protect themselves all year long 46% 13% 4% 32% 50% 14% 4% 23% 50% 22% 5% 22% 30% 31% 17% 35% 31% 23% 11% 33% 31% 19% 11% 6% 6% 35%18% 37% 4% 16% 44% 25% 15% 34% 32% 20% more often (after each bath / after sweating) 14% 33% 48% 15% 4% 21% 46% 25% 8% 15% 44% 32% 9% 18% 29% 34% 19% 49% 29% 13% 9% 27% 44% 14% 15% 27% 28% 27% 18% 24% 30% 24% 13% 9% 7% 34%14% 40% 5% 73% of people don’t protect themselves all year long the usefulness of sun protection on cloudy days outside europe europe outside europe outside europe europe europe europe (n=6000) : coverage in germany, france, spain, italy, uk, russia non-european countries (n=11001): coverage in asia (china, japan, indonesia), north america (usa, canada), latin america (brazil, mexico, argentina), af rica (south af rica, egypt) and australia. people using sunscreen even rarely : n=4837 in europe / n=8597 in non-european countries european at risk population(n=655) 44% do not think or don’t know if a protection is useful when the weather is overcast 56% 12% 32% 36% do not think or don’t know if a protection is useful when the weather is overcast yes 63% yes 47% skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 401 brief article eosinophilic annular erythema of childhood: a rare case mariana perez, md1, benjamin m. witkoff, do2, moises lutwak, md3, michael l. cohn, md5, eduardo weiss, md1-5 1florida international university, miami, fl 2larkin community hospital palm springs campus dermatology resident program, miami, fl 3larkin community hospital south miami campus dermatology resident program, miami, fl 4hollywood dermatology & cosmetic specialists, hollywood, fl 5department of pathology, memorial healthcare system, miami fl eosinophilic annular erythema (eae) of childhood is a rare and recurrent skin condition, with few cases described in the literature. the trunk and proximal extremities are mostly commonly affected.1–3 eae of childhood is characterized by the appearance of persistent, non-pruritic, urticarial annular lesions that enlarge in a centrifugal pattern.1,2,4,5 histopathology is often required for diagnosis, with lesions exhibiting a perivascular eosinophilic infiltrate concentrated in the dermis.1–3 this case report describes a rare case of eae of childhood in a newborn with associated neonatal eosinophilic pustulosis and laboratory abnormalities. the patient is a three-week-old male who was seen in the hospital for a generalized eruption distributed on the trunk and extremities, which developed four days following birth. the lesions were initially described as bright red targetoid plaques. after a few days, the lesions improved for a short period before recurring. due to worsening of the rash along with concomitant diarrhea with streaks of blood and concerns for dehydration, the patient was admitted for further work-up and supportive care. upon dermatologic exam, the patient had generalized annular erythematous plaques with elevated borders and without scaling (figure 1-2). the mother stated the lesions come and go and change abstract eosinophilic annular erythema (eae) of childhood is a rare and recurrent skin condition, with only a few cases described in the literature. the etiology of eae in children remains unclear. clinical presentation shows a persistent, non-pruritic, urticarial annular lesions that enlarge in a centrifugal pattern. biopsy is required for diagnosis which characteristically shows a perivascular eosinophilic infiltrate concentrated in the dermis. although there is considerable overlap between eae and annular erythema of infancy (aei), some proposed differences include age of onset, duration of lesions, presence of mucin deposition of histopathology, and time to resolution. this case report describes a rare case of eae of childhood in a newborn with associated neonatal eosinophilic pustulosis and laboratory abnormalities. introduction case report skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 402 in shape and distribution. in addition to the lesions on the trunk and extremities, multiple pustules over an eczematous base appeared on the bilateral cheeks and forehead. no lesions were noted on volar or mucosal surfaces. per the mother, the patient did not appear irritable. figure 1. annular erythematous plaques with elevated borders on the abdomen. the pregnancy was full term without history of autoimmune disease. the patient’s vitals remained stable throughout the hospital course. laboratory work-up showed consistent hypereosinophilia, peaking at 7,560 µl (36%) and elevated total immunoglobulin e (ige). subsequent allergic, immunologic, hematologic, gastrointestinal, and cardiac work-up was unremarkable. the clinical differential for the lesions on the trunk and extremities included eosinophilic dermatosis, eae of childhood, annular erythema of infancy (aei), neonatal eosinophilic pustulosis, erythema annularis centrifugum (eac), and neonatal lupus. a 3-0 punch biopsy was performed on the right lower extremity. histology showed mild spongiosis without parakeratosis and eosinophils interstitially and perivascularly in the dermis (figure 3a-c). pas stain was negative for fungi. there was no evidence of vasculitis or other significant inflammatory infiltrate. the histological differential included hypersensitivity reaction and allergic reaction. figure 2. annular erythematous plaques with elevated borders on the left lower extremity. based on clinical presentation and histologic description, the patient was diagnosed with eae of childhood in addition to the clinical diagnosis of neonatal eosinophilic pustulosis. he was started on triamcinolone 0.1% cream twice daily for lesions on the trunk and extremities and topical skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 403 clindamycin 1% twice daily to pustular lesions on the face. at one-week outpatient follow-up, lesions on both the face and body had improved. treatment was transitioned to hydrocortisone 2.5% cream twice daily to new lesions on the body. figure 3. punch biopsy of the right lower extremity (3a view at 100x, 3b view at 200x, 3c view at 400x). mild spongiosis without parakeratosis is present. no interface dermatitis is identified. 3b highlight dermal interstitial and perivascular eosinophils (orange arrow) with some lymphohistiocytic infiltrate as well (black arrow). eae of childhood is an extremely rare condition. there is considerable overlap between eae of childhood and aei, with some reports using the term interchangeably in children younger than one year as well as others describing eae as a variant of aei.1,2,5 some proposed differences include age of onset, duration of lesions, presence of mucin deposition on histopathology, and time to resolution (table 1).1,4–6 although there are features of aei in our patient clinically, histopathology favored eae. the biopsy demonstrated a predominant eosinophilic perivascular infiltrate, typical of eae, vs. the perivascular interstitial lymphohistiocytic infiltrate with some eosinophils seen in aei. furthermore, while early documented cases of aei were not typically associated with laboratory abnormalities, some cases of eae have been found to be associated with peripheral eosinophilia, as in our patient.3,7 eae has also been described as an annular variant of well’s syndrome (ws), or eosinophilic cellulitis. ws, however, is thought to be histopathologically characterized by a diffuse inflammatory infiltrate rather than perivascular inflammatory infiltrate, eosinophilic degranulation, the presence of flame figures (deposits of major basic protein and degenerated collagen) with surrounding granulomatous reaction, and vasculitis.1,2,4,5 additionally, resolution of ws lesions is associated with hyperpigmentation and/or residual atrophy, which is not typical for eae.1 neonatal lupus may also be included in the differential diagnosis, as it can present with subacute cutaneous lupus erythematosus-like annular erythematous plaques.8 however, these lesions are located in sun exposed areas (i.e. the face), have fine scaling, and are often associated with systemic findings such as congenital heart block, hepatobiliary involvement, and cytopenias. additionally, histopathology would show vacuolar interface changes, which were not seen on biopsy in our discussion skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 404 patient. finally, eac is another migratory annular erythema that can rarely occur in newborns, but prominent eosinophils are not noted on biopsy.4–6 the etiology of eae is unclear. it has been previously suggested that eae may be due to a hypersensitivity reaction, though no antigen has been identified. in children, eae has been diagnosed in association with asthma, though often no evidence for underlying disease is found.1 in early documented cases of aei, associated intestinal candida colonization and oral candidiasis was also reported.7,9 laboratory abnormalities can occur, though they are not required for diagnosis. peripheral eosinophilia has been reported in some cases;3 however, elevated ige levels have not been previously reported. interestingly, patients with neonatal eosinophilic pustolosis frequently present with peripheral eosinophilia.10 further, infants with hyperimmunoglobulin e (hyperige) syndrome can present with a crusting pustular eruption on the face and scalp similar to that of neonatal eosinophilic pustulosis, which would be associated with elevated ige levels and persistent eosinophilia.11 however, our patient lacked table 1. comparison of eosinophilic annular erythema (eae), annular erythema of infancy (aei), well’s syndrome (ws), and erythema annularis centrifugum (eac) skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 405 other findings of hyper-ige syndrome, such as coarse facial features, recurrent skin and sinopulmonary infections, severe eczema, and mucocutaneous candidiasis. eae may resolve spontaneously, be treated in the case of persistent lesions, or be recalcitrant to several therapies.2 due to its rarity, there are no established treatment recommendations, and previous treatments are based on the limited case reports with varying levels of success. previous reports have attempted topical and/or systemic steroids, hydroxychloroquine, chloroquine, cyclosporine, dapsone, indomethacin, tofacitinib, dupilumab, and uvb.1–4 recurrence has been noted in several reports. in our patient, topical mid-potency steroids appeared to resolve the lesions. to our knowledge, this is the earliest reported case of eae in a newborn and among few cases of eae reported in the pediatric population. our case is significant for its association with neonatal eosinophilic pustulosis, peripheral eosinophilia, and elevated ige. overall, this report provides new information to the limited knowledge surrounding this rare condition. conflict of interest disclosures: none funding: none corresponding author: edwardo weiss, md hollywood dermatology & cosmetic specialists 3850 hollywood blvd suite 403 hollywood, fl 33021 phone: (954) 961-1200 fax: 954.963.0378 email: eweiss1401@gmail.com references: 1. sempau l, larralde m, luna pc, casas j, staiger h. eosinophilic annular erythema. dermatology online journal. 2012;18(3). doi:10.5070/d33zs95220 2. thomas l, fatah s, nagarajan s, natarajan s. eosinophilic annular erythema: successful response to ultraviolet b therapy. clinical and experimental dermatology. 2015;40(8):883886. doi:https://doi.org/10.1111/ced.12668 3. gordon sc, robinson sn, abudu m, et al. eosinophilic annular erythema treated with dupilumab. pediatric dermatology. 2018;35(4):e255-e256. doi:https://doi.org/10.1111/pde.13533 4. rajput cd, nikam bp, hatkar nk. eosinophilic annular erythema in childhood: a distinct entity. indian journal of paediatric dermatology. 2021;22(3):250-253. doi:10.4103/ijpd.ijpd_98_20 5. toledo-alberola f, betlloch-mas i. annular erythema of infancy. actas dermosifiliográficas (english edition). 2010;101(6):473-484. doi:10.1016/s15782190(10)70832-5 6. palit a, inamadar ac. annular, erythematous skin lesions in a neonate. indian dermatol online j. 2012;3(1):45-47. doi:10.4103/22295178.93504 7. hebert aa, esterly nb. annular erythema of infancy. j am acad dermatol. 1986;14(2):339-343. doi:10.1016/s01909622(86)70039-x 8. derdulska jm, rudnicka l, szykutbadaczewska a, et al. neonatal lupus erythematosus – practical guidelines. journal of perinatal medicine. 2021;49(5):529-538. doi:doi:10.1515/jpm-2020-0543 9. stachowitz s, abeck d, schmidt t, ring j. persistent annular erythema of infancy associated with intestinal candida colonization. clinical and experimental dermatology. 2000;25(5):404-405. doi:https://doi.org/10.1046/j.13652230.2000.00675.x 10. hernández-martín á, nuño-gonzález a, colmenero i, torrelo a. eosinophilic pustular folliculitis of infancy: a series of 15 cases and review of the literature. j am acad dermatol. 2013;68(1):150-155. doi:10.1016/j.jaad.2012.05.025 11. ladrigan mk, leboit pe, frieden ij. neonatal eosinophilic pustulosis in a 2-month old. pediatric dermatology. 2008;25(1):52-55. doi:https://doi.org/10.1111/j.15251470.2007.00582.x skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 901 brief article cryoglobulinemia type i in patient with history of monoclonal gammopathy of unknown significance: a case report alexandra mathis, bs1, samantha marrone, md2 1 edward via college of osteopathic medicine, auburn, al 2 knipe dermatology, orlando, fl cryoglobulinemia vasculitis (cv) is a rare immune complex-mediated inflammation of blood vessels caused by proteins called cryoglobulins that precipitate from an individual's serum or plasma at temperatures lower than 37°c.1 due to the rarity of disease, heterogeneity of clinical presentations, and other associated lymphoproliferative disorders or infections, cryoglobulinemia can often be misdiagnosed before a correct diagnosis and treatment plan is made.2 here we describe a case of cryoglobulinemia type i in a patient with history of monoclonal gammopathy of unknown significance (mgus), cold induced urticaria, and other comorbidities. a 69-year-old black female presented to the dermatology clinic with a past medical history of monoclonal gammopathy of unknown significance (mgus), cold induced urticaria, hypertension, hyperlipidemia, and diabetes mellitus. history of present illness is significant for an 8-month history of dark discoloration associated with pain and bruising on her bilateral thighs. the patient stated the area worsened over time since her initial presentation. the patient denied fever, unexplained weight loss, myalgias, arthralgias, malaise, or enlargement of lymph nodes. she underwent previous evaluation at another clinic 2 months prior which included a shave biopsy from her right anterior proximal thigh that showed showed vasoocclusive disease with focal areas of epidermal necrosis, multiple small vessels with fibrin thrombi, minimal associated inflammation, with no evidence of leukocytoclasis. the patient was given abstract cryoglobulinemia is a form of vasculitis causing inflammation of the blood vessels due to aggregated proteins that clump together at cold temperatures, causing damage to skin, muscles, nerves, and other organs. an elderly black female presented with superficial ulceration with overlying eschar within areas of retiform purpura of her bilateral thighs present for 8 months. she was previously diagnosed with vaso-occlusive disease before presenting to our clinic for further evaluation and management. upon investigation, we have concluded that the patient has cryoglobulinemia type i. introduction case report skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 902 figure 1. superficial ulceration with overlying eschar within areas of retiform purpura of bilateral thighs. figure 2. site of 4mm punch biopsy on left thigh. skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 903 triamcinolone acetonide 0.1% topical cream twice daily with minimal improvement. physical examination showed superficial ulceration with overlying eschar within areas of retiform purpura of bilateral thighs (figure 1). two 4 mm punch biopsies were taken from her bilateral thighs (figure 2 and 3). h&e from the right thigh showed noninflammatory thrombosis compatible with cryoglobulinemia type i. biopsy of the left thigh stained with dif revealed intravascular deposition of igm, c3, and fibrinogen in the papillary vascular plexus with no deposition of igg or iga. the immunofluorescent pattern of single monoclonal antibody deposition (igm without igg) is suggestive of cryoglobulinemia type i. figure 3. site of 4mm punch biopsy on right thigh. laboratory work including ana, rheumatoid factor (rf), hepatitis panel (hepatitis b and c), hepatic function panel, complement components (c3c and c4c), and total complement were ordered. labs revealed negative ana, rf, and hepatitis panel (b and c); complement component c3c of 133 mg/dl (normal 83-193 mg/dl), complement component c4c of 5l (15-57 mg/dl), and total complement (ch50) of <13 l (range 31-60 u/ml) that was verified by repeat analysis. she was referred to hematology-oncology for further management and was treated with rituximab and a prednisone taper. at the 4 month follow up, she finished treatment and did well with no recurrence of symptoms. her laboratory values identified igg 1100, iga 237, igm 36, a free light chain kappa lambda ratio of 0.34, and a cryoglobulin serum level of 36. to date, she continues to be monitored by hematology and oncology for her cryoglobulinemia type i and mgus. cryoglobulinemia can be divided into type i, ii, or iii. type i consists of monoclonal immunoglobulins, whereas type ii and type iii, also referred to as mixed cryoglobulinemia, is a combination of polyclonal immunoglobulins with both monoclonal immunoglobulins and rheumatoid factor activity.3 the most predictive measure for cryoglobulinemia is based on the measurement of cryoglobulin coupled with low c4 complement level. our patient had both a low c4 and total complement level, suggestive of cryoglobulinemia. most cv patients have chronic hepatitis c, a finding more common in mixed discussion skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 904 cryoglobulinemia.4 mixed cryoglobulinemia is often associated with infections such as hepatitis b, hepatitis c, and hiv, autoimmune diseases such as sle and sjogren’s and lymphoproliferative disorders. however, our patient was unique in that she developed cryoglobulinemia vasculitis in the absence of hepatitis b and c. in the absence of hepatitis c infection, noninfectious origins such as lymphoproliferative disorders are commonly diagnosed among patients with cv.5 lymphoproliferative disorders, b cell diseases, and plasma cell dyscrasias such as multiple myeloma and monoclonal gammopathy of undetermined significance (mgus) are more common in cryoglobulinemia type i.3 our patient was previously diagnosed with mgus before the development of her cv, findings consistent with type i cryoglobulinemia. a french nationwide survey published by terrier b, et al. found that out of 64 patients with cryoglobulinemia type i, 28 patients also had a diagnosis of mgus.3 another study published by the british journal of hematology also found that out of 64 patients, 40% also had a diagnosis of mgus.6 the immunofluorescent pattern of single monoclonal antibody deposition (igm without igg) is suggestive of cryoglobulinemia type 1 whereas mixed cryoglobulinemia is composed of polyclonal immunoglobulins. in our patient, immunofluorescence showed deposition of only igm with no evidence of leukocytoclastic vasculitis, a finding which is normally seen in mixed cryoglobulinemia.7 type ii and iii (mixed) cryoglobulinemia can also be associated with rheumatoid factor (rf) activity which was negative in our patient. these biopsy and laboratory findings further suggest that this presentation is more likely cryoglobulinemia type i. type i cryoglobulinemia only accounts for 1015% of people with cryoglobulinemia whereas mixed constitutes the rest.8 type i is most associated with cutaneous involvement including recurrent episodes of purpuric eruptions, livedo reticularis, acrocyanosis, raynaud’s syndrome, and even severe infarction skin necrosis.9-11 renal and neurologic involvement are more frequent findings in patients with mixed cryoglobulinemia, findings not seen in our patient.8 based on presenting symptoms, physical exam findings, pathophysiology report from biopsy along with laboratory results, and current literature on cryoglobulinemia, we affirm and believe that this patient has cryoglobulinemia type i secondary to mgus who was successfully treated with rituximab and a prednisone taper. consent: patient consent was received prior to initiation of this case report and for usage of the photos and medical information within. conflict of interest disclosures: none funding: none corresponding author: alexandra mathis, bs edward via college of osteopathic medicine auburn, al email: amathis@auburn.vcom.edu references: 1. sidana s, rajkumar sv, dispenzieri a, et al. clinical presentation and outcomes of patients with type 1 monoclonal cryoglobulinemia. american journal of hematology. 2017;92(7):668-673. doi:10.1002/ajh.24745 2. de vita s, quartuccio l, isola m, et al. a randomized controlled trial of rituximab for the treatment of severe cryoglobulinemic vasculitis. arthritis & rheumatology. 2012;64(3):843-853. doi:10.1002/art.34331 3. terrier b, karras a, kahn j-e, et al. the spectrum of type i cryoglobulinemia skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 905 vasculitis. medicine. 2013;92(2):61-68. doi:10.1097/md.0b013e318288925c 4. bhandari j, awais m, aeddula nr. cryoglobulinemia. statpearls. https://www.ncbi.nlm.nih.gov/books/nbk557606/. published 2022. accessed january 10, 2023. 5. dammacco f, lauletta g, vacca a. the wide spectrum of cryoglobulinemic vasculitis and an overview of therapeutic advancements. clinical and experimental medicine. march 2022. doi:10.1007/s10238-022-00808-1 6. harel s, mohr m, jahn i, et al. clinico-biological characteristics and treatment of type i monoclonal cryoglobulinaemia: a study of 64 cases. british journal of haematology. 2014;168(5):671-678. doi:10.1111/bjh.13196 7. morra e. cryoglobulinemia. hematology. 2005;2005(1):368-372. doi:10.1182/asheducation-2005.1.368 8. murphy a, kilian a, lowe l, marder w. severe cutaneous necrosis associated with type i cryoglobulinemia. jaad case reports. 2019;5(8):736-738. doi:10.1016/j.jdcr.2019.06.020 9. brouet j-c, clauvel j-p, danon f, klein m, seligmann m. biologic and clinical significance of cryoglobulins. the american journal of medicine. 1974;57(5):775-788. doi:10.1016/0002-9343(74)90852-3 10. pascual m, perrin l, giostra e, schifferli ja. hepatitis c virus in patients with cryoglobulinemia type ii. journal of infectious diseases. 1990;162(2):569-570. doi:10.1093/infdis/162.2.569 11. liu py, prete pe, kukes g. leukocytoclastic vasculitis in a patient with type 1 cryoglobulinemia. case reports in rheumatology. 2011;2011:1-3. doi:10.1155/2011/124940 skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 225 research letter residency program websites as an avenue towards increasing diversity and inclusion in dermatology: a cross-sectional analysis of program websites ramon govea, bs,1 lauren c. hollins, md2 1 pennsylvania state college of medicine hershey, pa 2 department of dermatologypenn state hershey medical center hershey, pa in 2016, a call to action was made for increasing ethnic diversity in the field of dermatology1. from pre-medical programs to national medical organizations, initiatives have been constructed to address the lack of physicians from underrepresented minority (urm) groups. despite these efforts, only 4.6% and 6.6% of dermatology trainees in 2019-2020 are of “black or african american” and “hispanic, latino, or of spanish origin” respectively2. more efforts are needed if the field wishes to have a similar demographic representation to the nation, which is 13.4% black or african american and 18.5% latino or hispanic3. faculty appointments held by urms at academic centers are also declining4. thus, new methods of recruitment and retention in academia need to be explored. increasing applicant awareness of dermatology’s efforts to promote diversity and inclusion (d&i) can have the potential to attract more urm applications. one often utilized resource for information on residency programs is their website. our study analyzes current dermatology residency program (drp) websites to determine if d&i efforts and abstract background: in recent years, dermatology as a field has identified a paucity in diversity. multiple projects at different institutional levels were initiated to address this. one area of interest is recruitment of underrepresented minorities (urms) in medicine at the residency level. this study investigates how many dermatology residency programs display their diversity and inclusion (d&i) efforts on their official website. methods: 140 us dermatology residency program (drp) websites were analyzed for presence of d&i action items at all, and then specifically within their curriculum, goals, mission statements. the websites were reviewed for the presence of zero tolerance policies as well as targeted resources made available for urms in the residency program. results: as of december 2020, only 45/140 (32%) of residency programs mention d&i on their official websites. the least represented action item across all drp websites is the zero-tolerance policy for discrimination (3.6%). conclusions: most dermatology residency programs do not mention d&i on their websites. this can be a budget-friendly and effective method to recruit more diverse applicants to dermatology. as residency application seasons continue virtually, the program websites might be increasingly utilized as a source of information. introduction skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 226 commitments are mentioned on these websites. in december 2020, the american association of medical college’s (aamc) careers in medicine database was used to find all acgme-accredited drps. of these 143 programs, 140 had official websites. the primary outcome measured was the mentioning of d&i within mission statements, objectives, curricula, as well as trainee resources offered by the drp. proper judgement was used to determine whether the item was promoting any of the following: a diverse workforce, decrease in patient care disparities, increase in access or equitable patient care, focus on skin of color. the word “diversity” did not have to be present to meet the requirements. the presence of a zero-tolerance policy for discrimination was measured as well. program websites have multiple methods for distributing information. this study measured information provided directly through text on the drp website. information conveyed through other formats, such as videos and pdf files, was excluded. among the 143 listed drps in the aamc database, 140 (98%) were analyzed. figure 1 summarizes the results regarding each specific category where d&i was mentioned by the drps website. broad language regarding d&i was mentioned in 45/140 (32%) websites. this percentage only decreased when looking for more specific action items. the least represented action item across all drps is the zero-tolerance policy for discrimination. the field of dermatology is actively pursuing a more diverse workforce1,5, acknowledging the benefits of having physicians that reflect the demographics of our patient population. one approach to increasing diversity is with recruitment of urms medical students. residency programs use their website as a tool to provide information to prospective applicants. this study examined which acgme-accredited drps actively list their commitment to d&i. the data gathered shows that drps are currently underutilizing their website as a method to recruit urms. only 32% of drps mention d&i on their program websites. even less drp websites have d&i embedded in their program goals or curriculum (28% and 14% respectively). now, with the sars-cov-2 pandemic forcing virtual interview processes, it is imperative that residency programs use their website to recruit and display information that could be important to urms when developing their rank lists6. in conclusion, we encourage all drps to update their websites to demonstrate their commitment to d&i, as a simple, costeffective method that could lead to an increase the number of urm residents in the field of dermatology. this study presents limitations. by excluding information conveyed in formats other than direct text, some programs appeared to have less d&i items. methods results discussion conclusion skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 227 figure 1. percent of dermatology websites mentioning diversity and inclusion future studies are needed to determine how these changes correlate with urm applications and diversity in residency programs. conflict of interest disclosures: none funding: none corresponding author: lauren c. hollins, md 500 university drive hershey, pa 17033 office: 717-531-6049 email: lhollins@pennstatehealth.psu.edu references: 1. pandya ag, alexis af, berger tg, wintroub bu. increasing racial and ethnic diversity in dermatology: a call to action. j am acad dermatol. 2016 mar;74(3):584-7. doi: 10.1016/j.jaad.2015.10.044. epub 2016 jan 8. pmid: 26774427. 2. table b5. number of active md residents, by race/ethnicity, (alone or in combination) and gme specialty." aamc. 18 aug. 2021. web. association of american medical colleges. 3. quick facts: united states. race and hispanic origin. version: july 1, 2021. website. united states census bureau. 4. lett la, orji wu, sebro r. declining racial and ethnic representation in clinical academic medicine: a longitudinal study of 16 us medical specialties. plos one. 2018 nov 16;13(11):e0207274. doi: 10.1371/journal.pone.0207274. pmid: 30444928; pmcid: pmc6239326. 5. pritchett en, pandya ag, ferguson nn, hu s, ortega-loayza ag, lim hw. diversity in dermatology: roadmap for improvement. j am acad dermatol. 2018 aug;79(2):337-341. doi: 10.1016/j.jaad.2018.04.003. epub 2018 apr 10. pmid: 29653209. 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% mentionedzero tolerance policyembedded in mission statement, objectives, or goals embedded in curriculum targeted in resources offered diversity and inclusion on dermatology residency program websites present absent mailto:lhollins@pennstatehealth.psu.edu skin may 2022 volume 6 issue 3 (c) 2022 the authors. published by the national society for cutaneous medicine. 228 6. bernstein, simone a (10/2020). "graduate medical education virtual interviews and recruitment in the era of covid-19.". journal of graduate medical education (1949-8357), 12 (5), p. 557. treat-to-target outcomes and measures of treatment success in three phase 3 trials of tapinarof cream 1% once daily for mild to severe plaque psoriasis april w. armstrong,1 robert bissonnette,2 philip m. brown,3 anna m. tallman,3 kim a. papp4 1keck school of medicine, university of southern california, los angeles, ca, usa; 2innovaderm research inc., montreal, qc, canada; 3dermavant sciences, inc., morrisville, nc, usa; 4probity medical research inc., waterloo, on, canada introduction ■ treat-to-target strategies are used in several chronic diseases to improve outcomes1 ■ treatment goals for psoriasis have been recommended by the us national psoriasis foundation (e.g., achieving a percent body surface area [%bsa] affected of ≤1.0% at 3 months) and the european s3-guidelines on the systemic treatment of psoriasis (e.g., achieving a ≥75% decrease in psoriasis area and severity index [pasi75] within 3–4 months)1,2 ■ analyses of a large cohort of patients treated with systemic or biologic therapies (british association of dermatologists biologics and immunomodulators register) have shown that achieving an absolute pasi total score of ≤2 corresponded to achievement of a 90% decrease in pasi score (pasi90)3 ■ in clinical practice, many patients fail to meet treatment targets, and current topical treatments alone are generally insufficiently efficacious4,5 – even with use of approved systemic agents, alone or in combination, a global study found that 57% of patients with moderate to severe plaque psoriasis had not achieved clear/almost clear skin on current therapy6 ■ in addition, most topical therapies approved by the food and drug administration (fda) for psoriasis are restricted to ≤12 weeks of continuous use (e.g., ≤8 weeks for corticosteroids or calcipotriene, and ≤12 weeks for retinoids)7 ■ tapinarof (vtama®; dermavant sciences, inc., usa) is a first-in-class, non-steroidal, topical, aryl hydrocarbon receptor agonist approved by the fda for the treatment of plaque psoriasis in adults, and under investigation for the treatment of psoriasis in children down to 2 years of age and for atopic dermatitis in adults and children down to 2 years of age8 ■ tapinarof cream 1% once daily (qd) demonstrated statistically significant efficacy versus vehicle and was well tolerated in adults with mild to severe plaque psoriasis in two identical, 12-week, pivotal phase 3 trials, psoaring 1 (nct03956355) and psoaring 2 (nct03983980)9,10 – physician global assessment (pga) response (pga=0 or 1 and a ≥2-grade improvement from baseline by week 12) was achieved by 35.4% and 40.2% of the tapinarof-treated patients versus 6.0% and 6.3% of vehicle-treated patients, respectively (both p<0.0001) – pasi75 was achieved by 36.1% and 47.6% of the tapinarof-treated patients versus 10.2% and 6.9% of vehicle-treated patients by week 12, respectively (both p<0.0001) ■ in psoaring 3 (nct04053387), the long-term extension trial in which patients received intermittent or continuous tapinarof treatment, efficacy continued to improve beyond the 12-week trials, with a 40.9% rate of complete disease clearance (pga=0), ~4-month remittive effect off therapy, and durability of response on therapy of up to 52 weeks11 objective ■ to present analyses of treat-to-target outcomes for patients treated with tapinarof cream 1% qd in the psoaring trials, including more-aggressive targets of the proportion of patients achieving an absolute pasi total score of ≤1, ≤2, or ≤3, or a %bsa affected of ≤1% or ≤0.5% materials and methods trial design ■ pooled efficacy analyses included all patients who had a baseline pga score of ≥2 (mild or worse) before tapinarof cream 1% qd treatment in the psoaring trials (figure 1) ■ this included: – patients assigned to vehicle in psoaring 1 and 2 who received tapinarof in psoaring 3 – patients who received intermittent or continuous tapinarof treatment in psoaring 3 based on their pga score (where those who entered with, or achieved, a pga score of 0 discontinued treatment and were observed for remittive effect [maintenance of pga=0 or 1] while off therapy; if disease worsening occurred [pga≥2], tapinarof cream was restarted and continued until a pga=0 was achieved) figure 1. psoaring 1, 2, and 3 trial design *patients with pga=2 (mild) and pga= 4 (severe) limited to ~10% each of the total randomized population; ~80% of the total randomized population with pga=3 (moderate). †patients electing not to participate in the lte trial had a follow-up visit 4 weeks after completion of the treatment period. bsa, body surface area; lte, long-term extension; pga, physician global assessment; qd, once daily; r, randomized. endpoints and statistical analysis ■ proportion of patients who achieved a pasi total score of ≤3, ≤2, or ≤1 ■ proportion of patients who achieved a %bsa affected of ≤1.0% or ≤0.5% ■ efficacy analyses were based on pooled data from observed cases; time-to-event analyses were based on kaplan–meier estimates ■ the safety population included all patients who received tapinarof in the psoaring trials results baseline patient demographics and disease characteristics ■ overall, 915 eligible patients were included in the pooled efficacy analyses (table 1) ■ mean age was 50.2 years, 58.7% were male, mean weight was 92.2 kg, and mean body mass index was 31.6 kg/m2 ■ 78.1% had a pga score of 3 (moderate), mean pasi score was 8.7, and mean bsa affected was 7.8% table 1. baseline disease characteristics (pooled analysis) tapinarof cream 1% qd (n=915) pga, n (%) 2 – mild 127 (13.9) 3 – moderate 715 (78.1) 4 – severe 73 (8.0) pasi, mean (sd) 8.7 (4.2) bsa affected, %, mean (sd) 7.8 (5.0) bsa, body surface area; pasi, psoriasis area and severity index; pga, physician global assessment; qd, once daily; sd, standard deviation. achievement of absolute pasi total score of ≤3, ≤2, or ≤1 ■ pasi scores of ≤3, ≤2, and ≤1 were achieved by 75.0% (n=686), 66.9% (n=612), and 50.3% (n=460) of patients, respectively (figure 2) ■ the median time to target (95% confidence interval [ci]) was 58 (57–63) days, 87 (85–110) days, and 185 (169–218) days for achieving pasi ≤3, ≤2, and ≤1, respectively figure 2. proportion of patients achieving absolute pasi treatment targets (total score of ≤3, ≤2, or ≤1)* *median time to pasi ≤3: 58 (95% ci, 57–63) days; median time to pasi ≤2: 87 (95% ci, 85–110) days; median time to pasi ≤1: 185 (95% ci, 169–218) days. the analysis population included patients receiving intermittent treatment with tapinarof, due to the forced-withdrawal design of psoaring 3 (treatment withdrawal when patients achieved pga= 0). pooled analysis, oc. ci, confidence interval; oc, observed cases; pasi, psoriasis area and severity index; pga, physician global assessment; qd, once daily. achievement of %bsa affected of ≤1.0% or ≤0.5% ■ the analyses indicated that 61.3% of patients (n=561) achieved %bsa of ≤1.0%, with a median time to target of 120 (95% ci, 113–141) days (figure 3a) – in addition, 40% (95% ci, 37%–43%) achieved the guideline-recommended target1 of %bsa of ≤1.0% at 3 months (90 days) ■ %bsa of ≤0.5% was achieved by 49.7% (n=455) of patients, with a median time to target of 199 (95% ci, 172–228) days (figure 3b) figure 3. proportion of patients achieving bsa treatment targets (≤1.0% or ≤0.5%)* *median time to bsa ≤1.0%: 120 (95% ci, 113–141) days; median time to bsa ≤0.5%: 199 (95% ci, 172–228) days. the analysis population included patients receiving intermittent treatment with tapinarof, due to the forced-withdrawal design of psoaring 3 (treatment withdrawal when patients achieved pga= 0). pooled analysis, oc. bsa, body surface area; ci, confidence interval; oc, observed cases; pga, physician global assessment; qd, once daily. absolute pasi ≤1 and %bsa of ≤0.5% achieved by week 4 ■ figure 4 shows the clinical response for a patient with plaque psoriasis treated with tapinarof cream 1% qd, whose improvement by week 4 exceeded the absolute pasi, %bsa, and pga endpoints figure 4. total pasi, bsa, and pga scores at baseline, week 4, and week 12 in a patient with moderate plaque psoriasis treated with tapinarof cream 1% qd pga, pasi, and bsa are global efficacy assessments. example of one representative target lesion of one tapinarof-treated patient from the psoaring 2 clinical trial. individual results may vary. bsa, body surface area; pasi, psoriasis area and severity index; pga, physician global assessment; qd, once daily. safety ■ treatment-emergent adverse events (teaes) were mostly mild to moderate ■ the most common teaes (in ≥5% of patients) were folliculitis, contact dermatitis, and nasopharyngitis conclusions ■ tapinarof cream 1% qd was well tolerated and demonstrated rapid, clinically meaningful, and durable improvements in clinical efficacy in a high proportion of patients ■ treatment targets were achieved with tapinarof cream monotherapy, despite the challenges of meeting these goals with available systemic, biologic, topical, and combination therapies ■ the aggressive target of ≤1% bsa affected was achieved by 40% of tapinarof-treated patients within ~3 months; attainment continued to increase over time, with 50% of patients achieving this target at ~4 months ■ these findings support continuing tapinarof treatment beyond 3 months for patients who are experiencing improvement but not yet meeting the ≤1% bsa affected treatment target advocated by the national psoriasis foundation12 ■ an absolute pasi total score of ≤2 was achieved by 67% of tapinarof-treated patients; this is a treatment target that has been shown to correspond to a pasi90 response3 ■ these analyses may have underestimated the percentage of patients who achieved treatment targets, due to the unique forced-withdrawal design of psoaring 3 that resulted in intermittent rather than continuous treatment references 1. armstrong aw, et al. j am acad dermatol. 2017;76:290–298. 2. pathirana d, et al. j eur acad dermatol venereol. 2009;23:5–70. 3. mahil sk, et al. br j dermatol. 2020;182:1158–1166. 4. strober be, et al. dermatol ther. 2019;9:5–18. 5. bagel j and stein gold l. j drugs dermatol. 2017;16:1209–1222. 6. armstrong a, et al. j eur acad dermatol venereol. 2018;32:2200–2207. 7. elmets ca, et al. j am acad dermatol. 2021;84:432-470. 8. dermavant sciences. vtama (tapinarof) cream, 1%: us prescribing information. 2022. https://www.vtama.com/docs/dmvt_vtama_pi.pdf. accessed 22 july 2022. 9. lebwohl m, et al. n engl j med. 2021;385:2219–2229. 10. lebwohl m, et al. presentation at: european academy of dermatology and venereology; october 28 november 1, 2020. 11. strober b, et al. j am acad dermatol. 2022. https://doi.org/10.1016/j.jaad.2022.06.1171. 12. national psoriasis foundation. treat to target. https://www.psoriasis.org/treat-to-target/. accessed august 2022. acknowledgments this trial was funded by dermavant sciences, inc. the authors thank the participating investigators, patients and their families, and colleagues involved in the conduct of the trial. a.w.a. is a research investigator and/or scientific advisor to abbvie, boehringer ingelheim, bristol myers squibb, dermavant sciences, inc., dermira, epi, incyte, janssen, leo pharma, eli lilly, modmed, novartis, ortho dermatologics, pfizer, regeneron, sun pharma, sanofi, and ucb biopharma. r.b. has served as a consultant/ investigator/advisory board member for abbvie, alumis, almirall, amgen, anaptysbio, arcutis, aristea, bausch health, boehringer ingelheim, boston pharmaceuticals, bristol myers squibb, dermavant sciences, inc., eli lilly, escalier, janssen, kyowa kirin, leo pharma, nimbus, novartis, pfizer, regeneron, sienna, and ucb biopharma; and is an employee and shareholder of innovaderm research. p.m.b., and a.m.t. are employees of dermavant sciences, inc., with stock options. k.a.p. is a consultant/ speaker/scientific officer/has attended advisory boards for, or received grants or honoraria from, abbvie, akros, amgen, anacor, arcutis, astellas, bausch health/valeant, baxalta, boehringer ingelheim, bristol myers squibb, can-fite biopharma, celgene, coherus, dermira, dow pharma, eli lilly, evelo, galapagos, galderma, genentech, gilead, glaxosmithkline, janssen, kyowa kirin, leo pharma, medimmune, meiji seika pharma, merck (msd), merck-serono, mitsubishi pharma, moberg pharma, novartis, pfizer, prcl research, regeneron, roche, sanofi-aventis/genzyme, sun pharma, takeda, and ucb biopharma. editorial and medical writing support under the guidance of the authors was provided by apothecom, uk, and was funded by dermavant sciences, inc. in accordance with good publication practice (gpp3) guidelines (ann intern med. 2015;163:461–464). contact dr april w. armstrong at april.armstrong@med.usc.edu/aprilarmstrong@post.harvard.edu with questions or comments. adult patients with mild to severe plaque psoriasis • aged 18–75 years old • pga score ≥2* • bsa ≥3% to ≤20% double-blind treatment (12 weeks) 2:1 2:1 tapinarof 1% qd (n=340) tapinarof 1% qd (n=343) vehicle qd (n=170) vehicle qd (n=172) (n=510) (n=515) r r off treatment off treatment pga=0 (n=79) pga=0 stop treatment pga≥2 re-start treatment pga≥1 (n=680) tapinarof 1% qd long-term open-label extension (40 weeks)† follow-up (4 weeks) a. pasi score of ≤3 b. pasi score of ≤2 c. pasi score of ≤1 0 10 20 30 40 50 60 70 80 tapinarof 1% qd (686/915) 0 10 20 30 40 50 60 70 80 tapinarof 1% qd (612/915) p ro p o rt io n o f p at ie n ts , % p ro p o rt io n o f p at ie n ts , % p ro p o rt io n o f p at ie n ts , % 0 10 20 30 40 50 60 70 80 tapinarof 1% qd (460/915) 75% 67% 50% a. bsa of ≤1.0% 0 10 20 30 40 50 60 70 80 tapinarof 1% qd (561/915) 61% p ro p o rt io n o f p at ie n ts , % b. bsa of ≤0.5% 0 10 20 30 40 50 60 70 80 tapinarof 1% qd (455/915) 50% p ro p o rt io n o f p at ie n ts , % • • • pasi=14.7 • bsa=15.3% • pga=3 baseline week 4 week 12 • pasi=10.9 • bsa=0.3% • pga=1 • pasi=0 • bsa=0% • pga=0 skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 448 skimages allergic contact dermatitis to paraphenylenediamine in black henna christopher d. markeson, bs1, nicholas d. brownstone, md2, jennifer j. parker, md, phd2, sylvia hsu, md2 1 lewis katz school of medicine at temple university, philadelphia, pa 2 lewis katz school of medicine at temple university, department of dermatology, philadelphia, pa we present a case of a 19-year-old woman presenting with a blistering eruption on the bilateral dorsal forearms and dorsal hands. two weeks prior, the patient applied black henna to her skin without an adverse reaction. one week after the application of the black henna, the patient developed a pruritic, erythematous bullous eruption, confined to the area of henna placement (fig 1.) paraphenylenediamine (ppda) is a chemical additive used to create a dye used in black rubber, dark textiles and cosmetics, photographic ink, and black henna. ppda in its fully oxidized form is not an allergen sensitizer. for ppda to convert from its odorless, colorless form to the darkened hue skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 449 used as a dye, the base must undergo oxidation which creates free radicals in the epidermis [1]. upon exposure to the offending byproduct, previously sensitized individuals develop a type iv hypersensitivity reaction, typically within 48-72 hours after repeated exposure. reactivity to ppda is thought to be approximately 4-6.2% with variation seen between different regions of the world. the prevalence of ppda allergy is highest in hairdressers, hairdressing clients undergoing dye application, and photographic film developers due to repeated exposure. cosmetic practices, such as black henna and hair darkening, make up the majority of reported cases of ppda allergic contact dermatitis. “black henna” combines natural henna with various amounts of ppda ranging from 0.6% to 29.5%, well above the 2.0-6.0% recommended for use in hair dyes. among users of black henna, induction of allergic contact dermatitis is an estimated 2.5% per application [2]. patients with allergies to ppda may have co-sensitization to chemicals containing amide groups fixated in the para position on a benzene ring. sulfonamides and sulfonylureas are the most common class of medications shown to have cross-reactivity potential, with 6.0% of ppda-sensitized patients reacting to these medication classes [3]. in addition to these medical treatments, cross-reactivity has been seen in local anesthetizing agents containing benzocaine and similar amino ester group topical anesthetics. para-aminobenzoic acid, also known as paba, has historically been used in sunscreen for its uvb-absorbing properties but has fallen out of favor due to its sensitization potential. additionally, paraben-containing products have been shown to rarely cause cross-reactivity, with less than 3% of all ppda sensitized patients showing a reaction to parabens on patch testing [4]. the use of synthetic hair dye and black henna has increased over the past 15 years. increased ppda concentration in products has been shown to increase sensitization potential, severity of an allergic reaction, and the risk of co-sensitization. in patients with ppda sensitivity, patch testing is recommended to determine cross-reactivity. ppda-free hair dyes may contain paratoluenediamine sulfate (ptds), an alternative that is tolerated by only 50% of ppda-sensitive patients. it is important to educate patients on the potential side effects of these cosmetic alterations and provide alternatives to decrease morbidity. conflict of interest disclosures: none funding: none corresponding author: nicholas brownstone, md lewis katz school of medicine at temple university department of dermatology 3401 n. broad street outpatient building, 5th floor philadelphia, pa, 19140 email: nickbrownstone34@gmail.com references: 1. zanoni, thalita b., et al. "the oxidation of pphenylenediamine, an ingredient used for permanent hair dyeing purposes, leads to the formation of hydroxyl radicals: oxidative stress and dna damage in human immortalized keratinocytes." toxicology letters 239.3 (2015): 194-204. 2. mukkanna ks, stone nm, ingram jr. paraphenylenediamine allergy: current perspectives on diagnosis and management. j asthma allergy. 2017 jan 18;10:9-15. doi:10.2147/jaa.s90265. pmid: 28176912; pmcid: pmc5261844. 3. laberge l, pratt m, fong b, gavigan g. a 10year review of p-phenylenediamine allergy and related para-amino compounds at the ottawa patch test clinic. dermatitis. 2011 novskin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 450 dec;22(6):332-4. doi: 10.2310/6620.2011.11044. pmid: 22653006. 4. laberge l, pratt m, fong b, gavigan g. a 10year review of p-phenylenediamine allergy and related para-amino compounds at the ottawa patch test clinic. dermatitis. 2011 novdec;22(6):332-4. doi: 10.2310/6620.2011.11044. pmid: 22653006. winter clinical dermatology conference hawaii® • january 14-19, 2022 • kauai, hi introduction • actinic keratosis (ak) lesions occur primarily on visible, sun-exposed areas such as the face and scalp and may negatively affect health-related quality of life (hrqol) • common treatments are also associated with severe local skin reactions (lsrs)1,2 that may further impact hrqol and treatment adherence2-5 • therefore, it is vital to consider patient experiences and preferences when weighing treatment options • tirbanibulin demonstrated safety and efficacy in treating ak in phase 3 clinical trials6 • in 2021, a consensus meeting generated an ak-specific expert panel questionnaire (epq), which includes questions about skin appearance, lsrs, and treatment satisfaction, to complement the validated skindex-16 and treatment satisfaction questionnaire for medicine (tsqm-9) tools • here we describe the protocol for the patient-reported outcomes for actinic keratosis (proak) study objective • to assess the impact of tirbanibulin on patient-reported outcomes for patients with ak in real-world settings conclusions • the real-world proak study will gather insights into patient experiences with tirbanibulin as a treatment for ak using validated health-related pro measures and a recently developed epq • this new epq was developed to capture disease-specific patient perspectives and meaningful outcomes to patients that may not be fully reflected in existing questionnaires design • this a prospective cohort study enrolling 300 participants ≥18 years with ak on the face or scalp treated with tirbanibulin 1% ointment from 50 community practices across the united states (figure 1) patient inclusion criteria • diagnosed with ak of the face and scalp • has clinically typical, visible, and discrete ak lesions • considered as a potential candidate for tirbanibulin treatment to manage their ak • male or female, aged 18 years and above at the time of initiation of treatment with tirbanibulin • willing to avoid excessive sun or uv exposure and/or use relevant sunscreen protection and protective clothing during the study duration • able to read and write english • provide consent to participate in the study key exclusion criteria • patients with any dermatological condition of the face or scalp that could interfere with the clinical evaluations • hypertrophic ak lesions, open wounds, or suspected skin cancers within close proximity of the treatment area assessments • the primary endpoint is patient-reported outcomes at week 8 assessed by skindex-16, with additional endpoints described in figure 2 • recognizing the need for an ak-specific patient-reported outcome (pro) instrument, the epq (figure 3) was developed during a consensus advisory board held in 2021; after discussion of proposed questions, revisions were made and consensus on all items was reached by all 9 advisers • lsrs will be documented by clinicians and, in a subset of sites, will be photographed and have severity graded by clinicians; this subset of patients will also be asked to record a 1to 3-minute audio narrating their experience with treatment • tirbanibulin safety and tolerability will be monitored throughout the study figure 1. proak study design. ak, actinic keratosis; epq, expert panel questionnaire; pro, patient-reported outcome. figure 2. comparison of questionnaires used to assess outcomes. tsqm, treatment satisfaction questionnaire for medicine. figure 3. actinic keratosis–specific questionnaire. ak, actinic keratosis; epq, expert panel questionnaire. at a subset of sites, photographs will be captured to assess the progression of lsrs visit 1: confirm patient eligibility, obtain informed consent/assent, baseline data collection visit 2: assessment of ak clinical status, pros, effectiveness/safety, perceptions visit 3: assessment of ak clinical status, pros, effectiveness/safety, perceptions 5-day tirbanibulin 1% ointment treatment epq epq skindex-16 tsqm-9 week 0 week 8 week 24 week 1 week 2 week 4 skindex-16 number of items: 16 6-point scale (never bothered to always bothered) • signs and symptoms (itching, burning, hurting, irritation, persistence/ recurrence, appearance) • emotional impact (worry about condition, frustration, embarrassment, being annoyed, feeling depressed) • impact on interactions with others, desire to be with people, showing affection, daily activities, work or other activities tsqm-9 number of items: 9 7-point scale (extremely dissatisfied to extremely satisfied) or 5-point (not at all confident to extremely confident) scales • prevent/treat condition and relieve symptoms • time to treatment effect • convenience and ease of use • treatment satisfaction • confidence in benefits of treatment epq number of items: 11 consensus reached by 9/9 advisers patient-reported 1. overall appearance 2. satisfaction with improvement in appearance 3. satisfaction with improvement in texture 4. satisfaction with duration of skin reactions 5. severity of skin reactions compared to previous treatment 6. impact on daily activities compared to previous treatment 7. convenience and ease of use 8. overall satisfaction 9. likelihood of retreating with tirbanibulin clinician-reported 10. overall improvement in ak 11. severity of photodamage in treated area presenting author: brian berman; bbmdphd@gmail.com patient-reported outcomes for tirbanibulin effectiveness and safety in actinic keratosis in real-world settings: proak study protocol brian berman,1 april armstrong,2 mark lebwohl,3 ayman grada,4 neal bhatia,5 vishal a. patel,6 darrel rigel,7 james del rosso,8 todd schlesinger,9 leon kircik,3 raidah salem,4 ismail kasujee10 1university of miami miller school of medicine, miami, fl, usa; 2keck school of medicine university of southern california, los angeles, ca, usa; 3icahn school of medicine, mount sinai, new york, ny, usa; 4almirall llc, malvern, pa, usa; 5therapeutics clinical research, san diego, ca, usa; 6george washington school of medicine and health sciences, washington, dc, usa; 7nyu grossman school of medicine, new york, ny, usa; 8jdr dermatology research/thomas dermatology, las vegas, nv, usa; 9clinical research center of the carolinas, charleston, sc, usa; 10almirall sa, barcelona, spain acknowledgments: this study is supported by almirall, llc. medical writing, editorial assistance, and graphical support for this poster were provided under the direction of the authors by medthink scicom and funded by almirall, llc. references:1. jansen mhe, et al. n engl j med. 2019;380(10):935-946. 2. balcere a, et al. medicina (kaunas). 2019;55(92):1-8. 3. del rosso jq, et al. j clin aesthet dermatol. 2014;7(9):s2-s12. 4. del rosso j, et al. j drugs dermatol. 2021;20(8):888-893. 5. goldenberg g. j eur acad dermatol venereol. 2017;31(suppl 2):12-16. 6. blauvelt a, et al. n engl j med. 2021;384(6):512-520. disclosures: bb has served as an investigator, speaker, advisory board member , or consultant for aclaris, almirall, aiviva biopharma, biofrontera, evommune, ferndale laboratories, inc., galderma laboratories, l.p., glaxosmithkline, lemonex, leo pharma, mediwound, mino labs, miragen, novan, novartis pharmaceuticals corp., pierre fabre, phd biosciences, pulse biosciences, sensus, sirnaomics. aa served as a research investigator and/or scientific advisor to abbvie, bi, bms, epi, incyte, leo, ucb, janssen, lilly, novartis, ortho dermatologics, sun, dermavant, dermira, sanofi, regeneron, and pfizer. ml receives research funding from abbvie, amgen, arcutis, avotres, boehringer ingelheim, dermavant sciences, eli lilly, incyte, janssen research & development, llc, ortho dermatologics, regeneron, and ucb, inc., and is a consultant for aditum bio, almirall, altrubio inc., anaptysbio, arcutis, inc., aristea therapeutics, arrive technologies, avotres therapeutics, biomx, boehringer-ingelheim, bristol-myers squibb, cara therapeutics, castle biosciences, corrona, dermavant sciences, dr. reddy’s laboratories, evelo biosciences, evommune, inc., facilitatation of international dermatology education, forte biosciences, foundation for research and education in dermatology, helsinn therapeutics, hexima ltd., leo pharma, meiji seika pharma, mindera, pfizer, seanergy, and verrica. ag was the head of r&d and medical affairs at almirall, us. nb has been an investigator for sun pharma., j&j, amgen, arcutis, bms, atacama therapeutics, abbvie, ucb, mc2 therapeutics, foamix, sanofi/ regeneron, dermira, brickell biotech, soligenix, sol-gel tech., pfizer, menlo therapeutics, dusa pharma, leo pharma us; nb has also been a consultant for: ferndale laboratories, biofrontera ag, amirall, sun pharmaceutical industries, la roche-posay, mayne pharma group, ortho derm., sanofi/regeneron, isdin, galderma laboratories, vyome therapeutics limited, epi health, dermavant sciences, dermtech inc, sonoma pharm, castle biosciences; he has also been paid on the advisory board for dr. reddy. vap has received honoraria from regeneron and almirall; has served as a consultant for phd biosciences and jounce therapeutics; and has served as a speaker for regeneron and sanofi. dr has no disclosures to provide. jdr has served as a research investigator, consultant/advisor, or speaker for abbvie, aclaris, almirall, amgen (celgene), anaptysbio, arcutis, athenex, bausch (ortho dermatology), biofrontera, biopharmx, biorasi, blue creek, botanix, brickell, bristol myers squibb, cara therapeutics, cassiopea, dermata, dermavant, encore, epi health, ferndale, galderma, genentech, incyte, jem health, leo pharma, la roche-posay, lilly (dermira), mc2, novan, pfizer, ralexar, regeneron, sanofi-genzyme, sente, solgel, sonoma (intraderm) sun pharma, ucb, verrica, and vyne (foamix/menlo). ts reports receiving grant/research funding from abbvie, aclaris, allergan, anterios, aobiome, arcutis premier research, astellas pharma us, inc, athenex, biofrontera, biorasi, boehringer ingelheim, brickell biotech, bristol-myers squibb, cara therapeutics, castle bioscience, celgene, centocor ortho biotech (now janssen biotech), chemocentryx, coherus biosciences, concert pharmaceutical, corrona, cutanea life sciences, dermavant, dermira, dt pharmacy & dt collagen (melasma), epi health, galderma (nestle), janssen pharmaceuticals, inc, kiniksa, leo, lilly, merz, nestle skin health, nimbus, novartis, pfizer, processa, pulse biosciences, regeneron, sanofi genzyme, sisaf, and trevi; has received honoraria from abbvie, allergen, almirall, biofrontera ag, bristol-myers squibb, castle bioscience, epi health, foundation for research and education in dermatology (fred), galderma (nestle), merz, novartis, regeneron, and sun pharma; and has served as a speaker, advisory board member, or consultant for abbvie, allergan, almirall, amgen, biofrontera ag, bristol-meyers squibb, castle bioscience, celgene, cms aesthetics dcme, dusa/sun pharma, epi health, foundation for research and education in dermatology (fred), genentech, greenway therapeutix, kintor, merz, nextphase, novartis, pharmatecture, prolacta biosciences, pulse biosciences, regeneron, remedly, inc, sanofi genzyme, sun pharma, ucb, and verrica; has received consulting fees from lilly, ortho dermatologics, pierre fabre, plasmed, regeneron, and skinceuticals/l’oreal; has been involved in the cme program for med learning group; has been involved with onclive ssc insights filming/stacy jaffe for mjh associates; and owns stock in remedly, inc. lk has served as an investigator, speaker, advisory board member , or consultant for abbott laboratories; aclaris, inc; allergan, inc; almirall; anacor pharmaceuticals, inc; assos pharma; astellas pharma us, inc; asubio pharma co, ltd; berlex laboratories (bayer healthcare pharmaceuticals); biogen-idec, inc; biolife; biopelle; boehringer ingelheim; breckinridge pharma; celgene corporation; centocor, inc; colbar; collagenex; combinatrix; connetics corporation; coria; dermik laboratories; dermira, inc; dow pharmaceutical sciences, inc; dusa pharmaceuticals, inc; eli lilly & co; embil pharmaceutical co, ltd; eos; ferndale laboratories, inc; galderma laboratories, lp; genentech, inc; glaxosmithkline, plc; health point ltd; idera, inc; innocutis medical, llc; innovail; intendis, inc; johnson & johnson; laboratory skin care, inc; leo pharmaceuticals, inc; l’oreal sa; 3m; maruho co, ltd; medical international technologies; medicis pharmaceutical corp; merck & co, inc; merz; nano bio corporation; novartis pharmaceutical corporation; noven pharmaceuticals, inc; nucryst pharmaceuticals corporation; obagi medical products, inc; onset; ortho dermatologics; orthoneutrogena; pediapharma, inc; promius pharma, llc; pharmaderm; pfizer, inc; puracap; qlt, inc; quatrix; quinnova; serono (merck-serono international sa); skinmedica, inc; stiefel laboratories, inc; sun pharmaceutical industries, ltd; taro; tolerrx, inc; triax; ucb, inc; valeant pharmaceuticals north america llc; warner-chilcott; xenoport, inc; and zage. rs is an employee of almirall, us. ik is an employee of almirall, spain. (5-pt scale: much worse to much improved) (5-pt scale: much shorter to much longer) (5-pt scale: very unlikely to very likely) (5-pt scale: much better with tirbanibulin to much worse with tirbanibulin (5-pt scale: not cleared to completely cleared) (4-pt scale: absent to severe) (7-pt scale: extremely dissatisfied to extremely satisfied) powerpoint presentation non-invasive genomic profiling of pigmented lesions – an interim registry analysis greg stevens dmsc fellow, pa-c1, burkhard jansen, md1, terry arnold, mba, pa-c1, james rock, ms1, jennifer wood, dmsc, pa-c1, mark hyde, phd, pa-c1, loren clarke, md1 presented at the fall clinical dermatology conference october 20th – 23rd, 2022 1. dermtech, 11099 north torrey pines road, suite 150 la jolla, ca 92037, usa background: pigmented lesion analysis remains a challenging aspect of dermatology. the dermtech melanoma test (‘the test’) is a non-invasive gene-expression test designed to rule-out melanoma. it consists of the pigmented lesion assay, which detects rna products of long intergenic non-coding rna 00518 (linc00518) and preferentially expressed antigen in melanoma (prame), and an add-on assay for dna promoter mutations in telomerase reverse transcriptase (tert). in previous studies, the test was found to have a negative predictive value ≥99%. this registry study examines the real-world correlation of genomically atypical (test-positive) lesions with histopathologic diagnoses. methods: between april 2021 and march 2022, multiple geographically diverse sites throughout the us submitted data to a registry to assess real-world use of the test. approximately 8,000 clinically atypical lesions were tested. after receiving the test result, providers followed their clinical judgement for biopsy decision. histopathologic diagnoses for biopsied lesions were correlated with test results. results: among the approximately 8000 tests performed,1033 (12.9%) were positive. thirty-six did not have histopathologic diagnoses or confirmed test results available. of the 997 complete cases, 134 (13.4%) were diagnosed as melanoma; 89 (66.4%) were in situ and 45 (33.6%) were invasive. only 7 (5.2%) melanomas were beyond stage t1a. in addition, 73 (7.3%) positive lesions exhibited severe cytologic atypia or atypical junctional melanocytic hyperplasia histopathologically. conclusions: over 20% of lesions that tested positive were severely dysplastic, melanoma in situ, or invasive melanoma by histopathology. nearly 87% of clinically atypical lesions tested negative. almost all lesions diagnosed as melanoma were in situ or pt1a. this study demonstrates that the test guides appropriate biopsy decisions in real-world settings. abstract introduction and objective methods between april 2021 and march 2022, approximately 8000 lesions were entered into a nationwide registry from 63 unique sites. sites were encouraged to enter all results, including corresponding histopathology. histopathologic diagnoses were categorized first into melanoma and nonmelanoma. the melanomas were subcategorized into in situ and invasive, with the latter characterized by ajcc tumor size staging. among non-melanomas, the number of sdn/ajmh was determined. all uncertain cases were reviewed by a board-certified dermatopathologist. furthermore, correlation between number of genomic markers present to histopathologic diagnoses was calculated. the gene expression test is designed to rule out melanoma by analyzing noninvasively collected skin tissue from pigmented lesions for genomic atypia (linc00518, prame, and/or tert). the results of the test are designed to guide biopsy decisions on clinically suspicious lesions. this approach improves pigmented lesion management beyond visual inspection with a negative predictive value of ≥99% and a sensitivity of 91-97%, and by enriching melanoma among biopsied lesions almost 5-fold.1-3 the real-world performance of the test and its impact on clinical practice has been addressed in a previously completed 2020 patient registry, and summarized in 2 peer reviewed publications.3,4 the objective of this study was to better understand the real-world utility of the test using a nationwide registry. an interim analysis of this registry is presented here. 1. gerami p, yao z, polsky d, et al. development and validation of a noninvasive 2-gene molecular assay for cutaneous melanoma. j am acad dermatol. 2017;76(1):114-120.e2. 2. jackson sr, jansen b, yao z, ferris lk. risk stratification of severely dysplastic nevi by non-invasively obtained gene expression and mutation analyses. skin the journal of cutaneous medicine. 2020;4(2):105-110. 3. brouha b, ferris lk, skelsey, mk, et al. genomic atypia to enrich melanoma positivity in biopsied lesions: gene expression and pathology findings from a large u.s. registry study. skin. 2021;5(1),13–18. 4. brouha b, ferris lk, skelsey mk, et al. real-world utility of a non-invasive gene expression test to rule out primary cutaneous melanoma: a large us registry study. j drugs dermatol. 2020;19(3):257-262. 5. skelsey mk, brouha b, rock j, et al. non-invasive detection of genomic atypia increases real-world npv and ppv of the melanoma diagnostic pathway and reduces biopsy burden. skin. 2021;5(5), 512–523. references results genomic markers present 1 2 3 n % n % n % non-melanoma (excl. sdn/ajmh) 627 87.8% 157 64.6% 6 15.0% sdn/ajmh 45 6.3% 22 9.1% 6 15.0% melanoma 42 5.9% 64 26.3% 28 70.0% total 714 243 40 table 1. figure 1 of the approximately 8000 lesions entered into the registry from april 2021 to march 2022, 1033 (12.9%) were positive for at least one genomic biomarker. thirty-six of these lesions did not have histopathologic diagnoses or confirmed test results available. of the 997 complete cases, 134 (13.4%) were diagnosed as melanoma; 89 (66.4%) were in situ and 45 (33.6%) were invasive. only 7 (5.2%) melanomas were beyond stage t1a. in addition, 73 (7.3%) positive lesions exhibited severe cytologic atypia or atypical junctional melanocytic hyperplasia histopathologically. these results are depicted in the figure. as the number of genomic markers present increased, so did the percentage of both sdn/ajmh and melanomas. of note, the triple-positive cases (n=40) had a high likelihood of being either melanoma (n=28, 70%) or sdn/ajmh (n=6, 15%). these data are included in the table. ~8000 tests performed 1033 (12.9%) positive test results 997 (96.5%) records available 790 (79.2%) non-melanomas, excluding sdn/ajmh 134 (13.5%) melanomas 89 (66.4%) in situ 45 (33.6%) invasive 38 (84.4%) t1a 7 (15.6%) t1b – t2b 73 (7.3%) sdn/ajmh funding/disclaimer: all study sites were reimbursed by dermtech for the collection of data; the authors are employed by dermtech. conclusion this interim registry analysis demonstrates the real-world rate of positivity along with histopathologic correlation for this genomic test. over 20% of lesions that tested positive for any number of genomic markers were diagnosed histopathologically as melanoma or sdn/ajmh. the correlation increases markedly as more genomic markers are present (12.2% for one, 35.4% for two, and 85% for three). as sdn/ajmh are often treated similarly to early melanomas, this is data that can help clinicians with their management plans. sdn = severely dysplastic nevus ajmh = atypical junctional melanocytic hyperplasia scan qr code for additional peer-reviewed publications regarding this genomic test when paired with the previously shown negative predictive value of >99%,1,2,5 this study demonstrates the test’s clinical utility. the evidence suggests that the ideal use for this test is on clinically indeterminate lesions, where the tests addition adds the greatest value with minimal risk. skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 927 brief article atypical human papillomavirus infection with secondary tinea in a middle-aged caucasian male maulik m dhandha, md1, debjit ghosh, phd2, stephen tyring, md, phd3, peter rady, md, phd4 1 woodland clinic, woodland, ca 2 mgl group, rajkot, india 3 dermatology associates, houston, tx 4 university of houston, houston, tx human papillomavirus (hpv) infection is considered as one of the most common sexually transmitted infection (sti) and is caused by a double stranded deoxyribonucleic acid (dna) virus belonging to family papillomaviridae.1,2 in immunocompromised patients, the hpv infection can be persistent which leads to the development of genital warts and even cancers.3,4 tinea corporis is a superficial dermatophyte infection of the skin specially on the trunk and extremities except on the hands, feet, scalp, face and skin folds.5 herein we present a case of atypical diffuse cutaneous hpv infection in the setting of secondary tinea infection. a 51-year-old caucasian male with a past medical history of mild cytopenia, vasectomy and difficult socio-economic situation presented with chronic diffuse skin eruption for more than 3 years. the skin eruption was present all over the trunk and extremities. he described it as itchy and worse in summer. during the physical exam, we noticed scaly and some waxy pink to tan colored papules abstract we present a case of an atypical diffuse cutaneous eruption due to hpv infection and tinea in a 51-year-old male patient with a past medical history of mild cytopenia, vasectomy and difficult socio-economic situation. differential diagnosis at initial visit included epidermodysplasia verruciformis vs pityriasis rubra pilaris vs secondary syphilis vs xanthoma disseminatum vs atypical presentation of tinea vs less likely other. through clinical examination, repeat biopsy, tissue culture and extensive hpv testing, it was revealed that the patient had multiple hpv infections type fa52, 96, 16 and 13, with a possible secondary tinea infection. the patient was treated with antifungal medications first. topical cidofovir was recommended but not covered by insurance. the skin eruption improved gradually highlighting the importance of additional samples, tissue culture and extensive hpv testing in such atypical cases. our case describes the importance of multidisciplinary care to help patients with proper diagnostics and treatment regimens. introduction case report skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 928 and annular plaques on his shoulders, back, abdomen, genitalia and mucosal lips. the patient had a previous biopsy of the eruption that showed psoriasiform and spongiotic dermatitis with prominent parakeratosis, alternating areas of hypergranulosis, hypogranulosis and superficial perivascular lympho-eosinophilic infiltrate. periodic acidschiff (pas) stain was negative. prior treatment included triamcinolone cream that cured the itch but did not clear the eruption. the differential diagnosis at initial visit included epidermodysplasia verruciformis vs pityriasis rubra pilaris vs secondary syphilis vs xanthoma disseminatum vs atypical presentation of tinea vs less likely other. we first had the polymerase chain reaction (pcr)-based high-risk hpv test performed on the prior biopsy for hpv type 6,11,16,18,31,33,51 and it was negative. two repeat biopsies were conducted which showed mild epidermal hyperplasia with alternating parakeratosis and orthokeratosis, and granules within the stratum corneum with many small oval yeast forms and moderate hyphal elements, and mild superficial mixed dermal inflammation with eosinophils. differential diagnosis then included an infectious process, particularly a superficial secondary fungal infection (due to malassezia or dermatophyte species) with atypical granular parakeratosis (in view of atypical site of involvement). tissue culture was done that showed the growth of yeast. he was also examined for possible hiv and syphilis infection where the test results turned out to be negative. the patient was started on terbinafine 250 mg daily for 1 week along with ketoconazole shampoo as a body wash. adapalene was recommended to help if there was underlying atypical granular parakeratosis. hematology as well as infectious disease were consulted. per hematology, his pancytopenia was mild and not likely the cause of his skin eruption. extensive work up with them was unremarkable for any blood cell dyscrasias and/or malignancies. infectious disease subsequently treated the patient with fluconazole 200 mg weekly for 16 weeks, then itraconazole 200 mg twice daily for 10 days. there was however minimal to no clinical improvement in his condition and additional extensive hpv pcr testing was suggested on the second set of biopsies. subsequently, hpv typing by nested pcrs with fap 6 and pgmy-gp+ 7 primer systems were utilized. putative hpv pcr product was detected by fap primer system in the sample from the abdomen (figure 1a,i). presumed hpv pcr bands were visible by pgmy-gp+ primer system in the samples from both the abdomen and the arm (figure 1a,ii). the putative hpv-pcr products were purified, cloned, and sequenced. the acquired sequencing results were evaluated by computer assisted analysis using ncbiblast program. in one of the samples from the second set of biopsies, multiple infections with hpv isolate fa52 (closest sequence homology of known hpv type is beta hpv 150) (figure 1b), hpv type 96 (beta papillomavirus) (figure 1c), hpv type 16 (alpha papillomavirus) (figure 1d), and hpv type 13 (alpha, papillomavirus) (figure 1e) were detected. in the other sample, infection with hpv type 16 (alpha papillomavirus) (figure 1f) was identified. given these findings, we planned on treating the patient with topical cidofovir. we also recommended he get the hpv vaccine with his primary health care provider. during this time, the patient noticed that his skin eruption was starting to resolve. at a follow up visit it skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 929 figure 1. (a) i) hpv-pcr fragment obtained by fap nested pcr system: lanes m: fx174 rf dna marker, 1: biopsy from abdomen, 2: biopsy from arm 3: negative control dna, 4: positive control, cloned hpv type 5 dna fragment, 5: reagent control ii) hpv-pcr fragments obtained by pgmy-gp+ nested pcr system: lanes m: fx174 rf dna marker, 1: biopsy from abdomen, 2: biopsy from arm 3: negative control dna, 4: positive control siha dna, 5: reagent control (b) ncbi-blast aligment of sequencing data acquired from the fap hpv-pcr product (abdominal biopsy). the sequence data attained from clones #1 and #4-6 of patient’s hpv pcr dna fragment (query) showed 91% identities to the isolate hpv fa52 dna deposited into the ncbi genebank (sbjct). (c) ncbiblast aligment of sequencing data acquired from the fap hpv-pcr product (abdominal biopsy). the sequence data attained from the clone #3 of patient’s hpv pcr dna fragment (query) showed 95% identities to the prototype hpv 96 dna deposited into the ncbi genebank (sbjct). (d) ncbi-blast aligment of sequencing data acquired from the pgmy-gp+ hpv-pcr product (abdominal biopsy). the sequence data attained from the clones #1 , #3 and #4 of patient’s hpv pcr dna fragment (query) showed 99% identities to the hpv type 16 strain dna deposited into the ncbi genebank (sbjct). (e) ncbi-blast aligment of sequencing data acquired from the pgmygp+ hpv-pcr product (abdominal biopsy). the sequence data attained from the clones #2, #5, and #6 of patient’s hpv pcr dna fragment (query) showed 97% identities to the hpv type 13 prototype dna deposited into the ncbi genebank (sbjct). (f) ncbi-blast aligment of sequencing data acquired from the pgmy-gp+ hpv-pcr product (arm biopsy). the sequence data attained from the clones #1-6 of patient’s hpv pcr dna fragment (query) showed 99% identities to the hpv type 16 strain dna deposited into the ncbi genebank (sbjct) skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 930 figure 2. scaly and some waxy pink to tan colored papules and annular plaques on the (a) lower back, flanks, and buttocks and the (b) abdomen was about 70% improved with clear skin on the shoulders, upper back, mid back, and abdomen. few residual spots were present on lower back, buttocks, and upper extremities. he was still using the ketoconazole shampoo as a wash. given the spontaneous resolution and difficulty obtaining topical cidofovir, we decided to continue ketoconazole shampoo as a wash. a follow up phone call with the patient reported even more improvement in his skin condition. the present case report is a unique case of rare hpv infection phenotype presenting as an atypical cutaneous presentation with possible secondary tinea infection. it is difficult to explain the improvement in cutaneous eruption. one plausible explanation could be that the antifungals both topical and oral helped clear the secondary tinea. the hpv was then cleared through him developing immunity. the first biopsy did not show hpv or tinea. the present case highlights the importance of additional samples, tissue culture and extensive hpv testing in such atypical cases. it also highlights the importance of multidisciplinary care to help patients with proper diagnostics and treatment regimens. conflict of interest disclosures: none funding: none corresponding author: maulik manharlal dhanda, md woodland clinic woodland, ca email: maulikdhandha@gmail.com references: 1. milner da. diagnostic pathology: infectious diseases. elsevier health sciences. 2015. p. 40. 2. ljubojevic s, skerlev m. hpv-associated diseases. clin dermatol. 2014; 32: 227–234. 3. manini i, montomoli e. epidemiology and prevention of human papillomavirus. ann ig. discussion skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 931 2018;30 (4 suppl. 1):28-32. doi:10.7416/ai.2018.2231. 4. burd em, dean cl. human papillomavirus. microbiol spectr. 2016; 4. doi: 10.1128/microbiolspec.dmih2-0001-2015. 5. sahoo ak, mahajan r. management of tinea corporis, tinea cruris, and tinea pedis: a comprehensive review. indian dermatol online j. 2016; 7: 77–86. 6. forslund o, ly h, higgins g. improved detection of cutaneous human papillomavirus dna by single tube nested 'hanging droplet' pcr. j virol methods. 2003; 110: 129-136. 7. fuessel-haws al, he q, rady p, et al. nested pcr with the pgmy09/11 and gp5(+)/6(+) primer sets improves detection of hpv dna in cervical samples. j virol methods. 2004; 122: 87-93. powerpoint presentation tralokinumab demonstrated a consistent safety profile with up to 42 months of treatment in moderate-tosevere atopic dermatitis: including adverse events of special interest kristian reich1, eric simpson2, richard langley3, richard b warren4, antonio costanzo5, hidehisa saeki6, peter almgren7, le gjerum7, anna carlsson7, melinda gooderham8, andreas pinter9, marjolein de bruin weller10, and andrew blauvelt11 1translational research in inflammatory skin diseases, institute for health services research in dermatology and nursing, university medical center hamburg-eppendorf, hamburg, de; 2department of dermatology, oregon health & science university, portland, or, usa; 3division of clinical dermatology and cutaneous science, dalhousie university, halifax, nova scotia, ca; 4dermatology centre, salford royal nhs foundation trust and nihr biomedical research centre, the university of manchester, manchester, uk; 5dermatology unit department of biomedical sciences, humanitas university, milano, it; skin pathology laboratory, humanitas research hospital irccs, milano, it; 6department of dermatology, nippon medical school, tokyo, jp; 7leo pharma a/s, ballerup, dk; 8skin centre for dermatology, peterborough, on, ca; department of dermatology, queen's university, kingston, on, ca; probity medical research, waterloo, on, ca; 9department of dermatology, venereology, and allergology, goethe-universität frankfurt am main, frankfurt am main, de; 10department of dermatology and allergology, university medical center utrecht, heidelberglaan 100, 3584 cx utrecht, nl; 11oregon medical research center, portland, or, usa table 1. ecztend interim analysis baseline demographic and disease characteristics table 2. aesis in ecztend at april 30, 2021 data cut-off conclusions • this analysis of 1442 patients with up to 42 months of treatment supports the long-term benefit-risk profile of targeted il-13 inhibition with tralokinumab for patients with moderateto-severe ad, with no new safety signals identified • exposure-adjusted incidence rates of aes of special interest were generally similar to or lower than rates reported during the short-term, placebo-controlled period up to week 16 and declined over time • overall, tralokinumab demonstrated sustained long-term improvement in extent and severity of atopic dermatitis over 104 weeks of treatment in ecztend figure 1. ecztend study design (a) and patient cohorts in interim analyses (b) objective to report an interim safety analysis of patients treated with tralokinumab for up to 42 months, including adverse events of special interest (aesi) materials and methods study design and patient cohorts • ecztend is an open-label, 5-year extension trial including adult and adolescent patients with ad in 11 countries who previously participated in the tralokinumab pts ecztra 1-8 or the traski investigatorinitiated study • in ecztend, patients received open-label tralokinumab 300 mg q2w (home use) plus optional topical corticosteroids (tcs), with visits every 8 weeks (figure 1a) • interim safety analyses presented here include all patients transferred from ecztra 1-5 and 7; with patients having received up to 42 months maximum tralokinumab exposure (≤1 year in pts and ≤2.5 years in ecztend; safety analysis set, n=1442) (figure 1b) • ecztra 1/2: double-blinded, randomized, placebo-controlled, 52-week monotherapy trials • ecztra 3: double-blinded, randomized, placebo-controlled, 32-week tcs combination trial • ecztra 4: open-label, 14-week, drug-drug interaction (ddi) trial • ecztra 5: double-blinded, randomized, placebo-controlled, 16-week, vaccine antibody-response trial • ecztra 7: randomized, double-blinded, placebo-controlled, 26-week tcs combination trial in cyclosporin a (csa) refractory patients • interim efficacy analyses are also presented from the ecztend week 104 cohort (n=616), which includes all patients who reached the 2-year time point or would have reached that time point had they not discontinued earlier (figure 1b) endpoints and analyses • primary endpoint: number of aes during the treatment period from baseline of ecztend up to week 268 • secondary endpoints: proportions of patients achieving an investigator’s global assessment (iga) score of 0/1 (clear/almost clear) and >75% improvement in eczema area and severity index (easi-75) from week 16 to week 248 • a summary of the number of aes, the rate of aes, the number (percentage) of patients with any treatment-emergent adverse events (teaes), deaths, saes, and withdrawals from the trial due to aes are presented • aesis were predefined in the trial based on areas of safety interest for monoclonal antibodies in ad: skin infections requiring systemic treatment, eczema herpeticum, malignancies, and eye disorders. other safety areas of interest were captured retrospectively using meddra searches of all aes results patients, demographics, and clinical characteristics • patients had up to 42 months of tralokinumab exposure (including pts plus ecztend) with a median time on tralokinumab total of 131.5 weeks (approximately 31 months; iqr 83.4-161.8 weeks), at the time of data cut-off • long-term use of tralokinumab 300 mg q2w was well-tolerated, and no new safety signals were identified with up to 42 months of treatment relative to initial treatment in parent trials (figure 2) • the pattern of frequently reported aes in ecztend (≥5.0% of patients) was similar to that observed with tralokinumab in the pts, including viral upper respiratory tract infection, atopic dermatitis, upper respiratory tract infection, headache, and conjunctivitis (reported by preferred term) • no events of conjunctivitis aes were saes; only 4 patients discontinued due to conjunctivitis aes (0.3 %) figure 2. long-term use of tralokinumab 300 mg q2w was well-tolerated in ecztend references 1. nutten s. ann nutr metab. 2015;66(suppl 1):8-16; 2. weidinger s, novak n. lancet. 2016;387:1109-22; 3. popovic b, et al. j mol biol. 2017;429:208-19; 4. wollenberg a, et al. br j dermatol. 2021;184(3):437-449; 5. silverberg ji, et al. br j dermatol. 2021;184(3):450-463; 6. blauvelt a, et al. j am acad dermatol. 2022;s0190-9622(22)02345-3.disclosures kristian reich has served as advisor and/or paid speaker for and/or participated in clinical trials sponsored by abbvie, almirall, amgen, boehringer ingelheim, bristol-myers squibb, celgene, forward pharma, gilead, galderma, janssen-cilag, kyowa kirin, leo, lilly, medac, novartis, ocean pharma, pfizer, sanofi, ucb; professor reich is co-founder of moonlake immunotherapeutics. eric simpson reports grants and/or personal fees from abbvie, boehringer ingelheim, celgene, dermavant, dermira, eli lilly, fortébio, galderma, incyte, kyowa kirin, leo pharma, medimmune, menlo therapeutics, merck, novartis, ortho dermatologics, pfizer, pierre fabre dermo cosmetique, regeneron, sanofi, tioga, and valeant. richard langley has served and received compensation in the form of grants and/or honoraria as principal investigator for and is on the scientific advisory board or has served as a speaker for abbvie, amgen, boehringer ingelheim, celgene, eli lilly, janssen, leo pharma, merck, novartis, pfizer, and ucb. richard b warren has received research grants or consulting fees from abbvie, almirall, amgen, arena, astellas, avillion, boehringer ingelheim, bristol myers squibb, celgene, dice, eli lilly, gsk, janssen, leo pharma, medac, novartis, pfizer, sanofi, sun pharma, ucb, and union. he is supported by the manchester nihr biomedical research centre. antonio costanzo has received research grants or consulting fees from abbvie, almirall, amgen, boehringer ingelheim, bristol myers squibb, celgene, eli lilly, janssen, leo pharma, novartis, pfizer, sanofi, ucb. hidehisa saeki has received lecture fees from kyorin, kyowa kirin, leo pharma, mitsubishi tanabe, maruho, sanofi, tokiwa, and taiho; and scholarship donations from esai, mitsubishi tanabe, maruho, and torii. peter almgren, le gjerum, and anna carlsson are employees of leo pharma. melinda gooderham has been an investigator, speaker and/or advisor for: abbvie, amgen, akros, anaptysbio, aslan, arcutis, bausch health, bms, boehringer ingelheim, celgene, dermira, dermavant, eli lilly, galderma, gsk, incyte, janssen, kyowa kirin, leo pharma, medimmune, merck, novartis, pfizer, regeneron, roche, sanofi genzyme, sun pharma, and ucb. andreas pinter has served as an investigator and/or speaker and/or advisor for abbvie, almirall-hermal, amgen, biogen idec, biontec, boehringer-ingelheim, celgene, celltrion, gsk, eli-lilly, galderma, hexal, janssen, leo pharma, mc2, medac, merck serono, mitsubishi, msd, novartis, pascoe, pfizer, tigercat pharma, regeneron, roche, sandoz biopharmaceuticals, sanofi-genzyme, schering-plough and ucb pharma. marjolein s. de bruin-weller is a consultant/advisor for abbvie, lilly, pfizer, regeneron, sanofi genzyme, and ucb and has received grant/research support from regeneron and sanofi genzyme. andrew blauvelt has served as a speaker, scientific adviser, and / or clinical study investigator for abbvie, abcentra, aligos, almirall, amgen, anaptysbio, arcutis, arena, aslan, athenex, boehringer ingelheim, bristol-myers squibb, dermavant, ecor1, eli lilly, evommune, forte, galderma, highlightii pharma, incyte, janssen, landos, leo pharma, merck, novartis, pfizer, rapt, regeneron, sanofi genzyme, sun pharma, ucb pharma, vibliome, and xencor. acknowledgements this analysis was sponsored by leo pharma a/s. medical writing according and editorial support from alphabet health by meredith whitaker, phd was funded leo pharma a/s, ballerup, denmark, to good publication practice guidelines (https://www.ismpp.org/gpp3). richard b warren is supported by the manchester nihr biomedical research centre. this work was previously presented at eadv 2022. scan to download a copy of this poster copies of this poster and its content, obtained through this qr code, are for personal use only and may not be reproduced without written permission from the authors introduction • atopic dermatitis (ad) is a chronic and debilitating inflammatory skin disease requiring long-term treatment options with a favorable safety profile1,2 • tralokinumab, a first-in-class, fully human monoclonal antibody, specifically neutralizes il-13 with high affinity3 • phase 3 studies with tralokinumab have demonstrated favorable safety and sustained efficacy in adult patients with ad for up to 1 year4,5 • an ongoing extension trial, ecztend (nct03587805), is assessing the safety and efficacy of treatment with subcutaneous tralokinumab 300 mg every 2 weeks (q2w) following participation in a parent trial (pt) • with one additional year added to the previously published data6 this analysis further describes the safety profile of tralokinumab during long-term treatment figure 3. aesis in ecztend at april 30, 2021 data cut-off summary of aesis in ecztend • aesis were observed at rates similar to or lower than reported in pts (figure 3, table 2) • the most frequent eye disorder was conjunctivitis, including bacterial, allergic and viral types • there was no clustering in type of malignancy and none reported in more than 2 patients • there was no specific clustering in any type of skin infection requiring systemic treatment • other areas of interest, based on common concerns for those with ad, were: • injection site reaction: reported for 35 patients [2.4%, 2.5 vs 22.9 and 4.0 (ne/pye)*100 in ecztend vs pt tralokinumab and placebo] • rates for herpes simplex, oral herpes and herpes zoster: similar or lower than placebo up to week 16 and rates decreased over time [2.0/1.6/1.3 vs 5.2/3.1/1.4 and 3.7/8.1/2.0 (ne/pye)*100 in ecztend vs pt tralokinumab and placebo] abbreviations %, percentage of patients with ≥1 event; ad, atopic dermatitis; adj., adjusted; ae, adverse event; aesi, adverse event of special interest; dlqi, dermatology life quality index; e, number of adverse events; easi, eczema area and severity index; iga, investigator’s global assessment; locf, last observation carried forward; n, number of patients with ≥1 event; ne, number of events; np, number of patients; nri, non-responder imputation; nrs, numeric rating scale; pye, patient-years of exposure; pt, parent trial; q2w, every 2 weeks; tcs, topical corticosteroids. figure 4. proportion of patients achieving easi-75, iga 0/1, worst weekly pruritus nrs ≤3, and dlqi ≤5 with tralokinumab at week 104 site visit. iga, easi, scorad, worst weekly pruritus nrs, eczema-related sleep nrs, patient use of topical treatment screening and follow-up visits home use training poem, dlqi/cdlqi, eq-5d-5l ada/pharmacokinetic measurement weeks from first treatment in ecztend 5640322416 484 8–2 0 screening period tcs use allowed visit schedule until end of may 2021b sfu 16 weeks after last imp 24864 72 80 88 96 1042 12 patient cohorts in ecztend interim analysis april 30, 2021 data cut-off all patients who reached the 2-year time point (week 104) or would have reached that time point had they not discontinued earlier week 104 efficacy cohort (n=616) all patients transferred from ecztra 1, 2, 3, 4, 5, and 7; up to 42 months maximum tralokinumab exposure (≤1 year in pts and ≤2.5 years in ecztend) safety analysis set (n=1442) ecztend interim safety analysis set n=1442 age median years (iqr) 38.0 (27.0; 50.0) sex n (%) male female 831 (57.6) 611 (42.4) race n (%)a white black asian 1093 (75.9) 108 (7.5) 203 (14.1) parent trial n (%) ecztra 1 ecztra 2 ecztra 3 ecztra 4 ecztra 5 ecztra 7 450 (31.2) 293 (20.3) 282 (19.6) 31 (2.1) 149 (10.3) 237 (16.4) age at onset of ad median years (iqr) 3.0 (1.0; 15.0) duration of ad median years (iqr) 27.0 (18.0; 39.0) patients who permanently discontinued ecztend n (%) 330 (22.9) parent trial baseline ecztend baseline iga severity n (%) clear/minimal (score=0/1) mild (score=2) moderate (score=3) severe (score=4) 765 (53.1) 677 (46.9) 442 (30.6) 524 (36.3) 391 (27.1) 85 (5.9) easi median (iqr) 26.8 (20.5; 37.6) 4.8 (1.7; 12.0) scorad median (iqr) 67.7 (60.0; 77.9) 30.2 (18.7; 45.0) dlqib median (iqr), n 16.0 (11.0; 22.0), 1391 5.0 (2.0; 10.0), 1400 worst weekly pruritus nrsc median (iqr), n 7.9 (6.8; 8.8), 1257 5.0 (3.0; 7.0), 1440 aavailable in 1440 patients. bsubjects from the ecztra 4 parent trial did not have dlqi assessments in the parent trial, and thus are missing parent trial baseline for dlqi assessments. cin pts, worst pruritus nrs is assessed daily; in ecztend, worst pruritus nrs is assessed based on recall of the previous week before the visit. a b placebo, n=680 tralokinumab, n=1605 tralokinumab, n=1442 up to week 16 parent trialsa ecztend data cutoff apooled safety analysis set includes patients from parent trials ecztra 1, 2, 3, 5, and phase 2b. brate calculated by number of events divided by pye, multiplied by 100. cfor pts, cochran-mantel-haenszel weights were applied to calculate adjusted ae incidences and rates to account for different randomization ratios across pts. dconjunctivitis reported by preferred term. n (%) 449 (67.2) 1080 (65.7) 1127 (78.2) 18 (2.8) 37 (2.1) 101 (7.0) 20 (2.8) 38 (2.3) 34 (2.4) eczema herpeticum malignancies skin infections requiring systemic treatment eye disorders [conjunctivitisd] placebo, n=680 tralokinumab, n=1605 tralokinumab, n=1442 up to week 16 parent trialsa ecztend data cutoff apooled safety analysis set includes patients from parent trials ecztra 1, 2, 3, 5, and phase 2b. brate calculated by number of events divided by pye, multiplied by 100. cfor pts, cochran-mantel-haenszel weights were applied to calculate adjusted ae incidences and rates to account for different randomization ratios across pts. dconjunctivitis category includes several preferred terms, such as conjunctivitis, conjunctivitis allergic, conjunctivitis bacterial and conjunctivitis viral. aes in ecztend interim safety analysis set aes up to week 16 in parent trials initial tralokinumab treatmenta tralokinumab q2w + optional tcs (n=1442; pye=2446.2; 131.5 weeks median exposure) tralokinumab q2w ± tcs (n=1605; pye=473.2) placebo q2w ± tcs (n=680; pye=193.1) n (%) rateb [(np/pye)*100] e rate [(ne/pye)*100] n (adj. %)c e adj. rateb,c [(ne/pye)*100] n (adj. %)c e adj. rateb,c [(ne/pye)*100] eczema herpeticum 17 (1.2) 0.7 18 0.7 6 (0.3) 6 1.2 10 (1.5) 10 5.2 malignancies 8 (0.6) 0.3 8 0.3 1 (0.1) 1 0.2 0 (0) 0 0 skin infections requiring systemic treatment 36 (2.5) 1.5 51 2.1 42 (2.6) 46 9.7 35 (5.5) 42 22.8 eye disorders 132 (9.2) 5.8 174 7.1 132 (7.9) 155 31.1 22 (3.4) 24 12.9 conjunctivitisd 125 (8.7) 5.4 160 6.5 126 (7.5) 145 29.0 21 (3.2) 23 12.3 keratoconjunctivitis 8 (0.6) 0.3 8 0.3 5 (0.3) 5 1.2 0 0 0 keratitis 6 (0.4) 0.2 6 0.2 4 (0.2) 5 0.9 1 (0.2) 1 0.6 • tralokinumab demonstrated sustained long-term improvement in ad signs and symptoms in patients who reached the 2-year time point (week 104), or would have reached that time point had they not discontinued earlier, prior to data cutoff april 30, 2021 (figure 4) summary of safety in ecztend • long-term use of tralokinumab 300 mg q2w was well-tolerated, and no new safety signals were identified with up to 42 months of treatment relative to initial treatment in parent trials (figure 2) 5.2 0 22.8 12.9 1.2 0.2 9.7 31.1 0.7 0.3 2.1 7.1 0 5 10 15 20 25 30 35 r a te [( n e / p y e )* 10 0 ]b ,c 6.5 29 12.3 n (%) 10 (1.5) 6 (0.3) 17 (1.2) 0 (0.0) 1 (0.1) 8 (0.6) 35 (5.5) 42 (2.6) 36 (2.5) 22 (3.4) 132 (7.9) 132 (9.2) pt ecztend apooled safety analysis set includes patients from parent trials ecztra 1, 2, 3, 5, and phase 2b. brate calculated by number of events divided by pye, multiplied by 100. cfor pts, cochran-mantel-haenszel weights were applied to calculate adjusted ae incidences and rates to account for different randomization ratios across pts. dconjunctivitis category includes several preferred terms, such as conjunctivitis, conjunctivitis allergic, conjunctivitis bacterial and conjunctivitis viral. sustained improvement in ad signs and symptoms data is relative to baseline in parent trial, n=616. nrs refers to worst weekly pruritis nrs ≤3. the observed analysis includes data for all participants with a valid measurement at the indicated timepoint. the locf method imputes the value recorded at the participant’s last visit for subsequent missed timepoints. the modified nri method considers participants who discontinue from trial due to adverse event(s) or lack of efficacy as non-responders, and other missing are imputed with locf. https://www.ismpp.org/gpp3 as previously demonstrated for patients with psoriasis (2), this study showed that patients presenting atopic dermatitis are significantly improved at the end of a 3-week balneotherapy at la roche-posay thermal care center. reduced disease severity was associated with increase of microbiome diversity, reduction of staphylococcus, increase of xanthomonas genus, reduction of gram-positive and increase of gram-negative bacteria. s. seite, d. moyal la roche-posay dermatological laboratories, asnières, france objective methodology can the skin microbiota of patients suffering from atopic dermatitis be modified after balneotherapy? among the 7561 patients treated in 2016 with balneotherapy at la roche-posay thermal center, 27% presented with eczema or atopic dermatitis (ad). the objective of this study was to evaluate the efficacy of a balneotherapy at the thermal care center of la roche-posay for patients suffering from atopic dermatitis and to assess their skin microbiota evolution. we assessed the evolution of skin microbiota in ad patients, before and after 3 weeks of balneotherapy including high pressure filiform showers, baths, facial and body spray treatments as well as la roche-posay thermal water consumption. skin microbiota was sampled on one eczema lesion and one adjacent unaffected skin site on 35 atopic patients (31 ± 16 years old) to analyze microbiota diversity (shannon index), bacterial phyla and genus abundance as well as the severity of ad with scorad. results as previously shown, at the end of the balneotherapy period, the scorad improved from 54 ± 16 to 23 ± 10 (-56% in average)(1). at the bacterial level, before balneotherapy, the shannon diversity index was lower on the affected skin compared to the adjacent unaffected skin (2.52 +/0.41 vs 3.22 +/0.32). shannon index increased after balneotherapy and became similar on both areas (3.42 +/0.33 vs 3.89 +/0.26). in addition, after balneotherapy, the abundance of firmicutes was reduced in both areas and other phyla increased. the decrease of firmicutes was due to a significant reduction of staphylococci in both areas. lastly, an increase in the amount of xanthomonas genus was also observed. conclusion references 1 seite s. thermal waters as cosmeceuticals: la roche-posay thermal spring water example. clin cosm invest dermatol: 2013, 6: 23-28 2 martin r, henley jb, sarrazin p, seite s. skin microbiome in patients with psoriasis before and after balneotherapy at the thermal care center of la roche-posay. j drugs dermatol: 2015, dec: 14(12): 1400-1405 uaf af 100 300 500 700 900 1100 1300 1500 uaf af 100 300 500 700 900 1100 1300 1500 uaf uf 100 300 500 700 900 1100 1300 1500 streptococcus xanthomonas acinetobacter enhydrobacter staphylococcus unassigned corynebacterium micrococcus haemophilus [prevotella] neisseria klebsielle granulicatella veillonella rothia prevotella porphyromonas actinomyces peptoniphilus pseudomonas paracoccus leptotrichia chryseobacterium kocuria lactococcus anaerococcus unclassified finegoldia a b we noticed that balneotherapy had induced a significant increased of skin gram-negative bacteria and a significant decrease of gram-positive bacteria. 0 2 0 4 0 6 0 8 0 10 0 d0 d21 r el at iv e ab u n d an ce ( % ) a (gram-negative (uaf+af)) b (gram-positive (uaf+af)) 10 0 8 0 6 0 4 0 2 0 0 d0 d21 r el at iv e ab u n d an ce ( % ) unassigned streptococcus xanthomonas acinebacter enhydrobacter staphylococcus corynebacterium micrococcus haemophilus [prevotella] neissera klebsiella granulicatella veillonella rothia prevotella porphyromonas actinomyces peptoniphilus pseudomonas paracoccus leptotrichia chryseobacterium kocuria lactococcus anaerococcus uniclassified finegoldia streptococcus xanthomonas acinetobacter enhydrobacter staphylococcus unassigned corynebacterium micrococcus haemophilus [prevotella] neisseria klebsielle granulicatella veillonella rothia prevotella porphyromonas actinomyces peptoniphilus pseudomonas paracoccus leptotrichia chryseobacterium kocuria lactococcus anaerococcus unclassified finegoldia streptococcus xanthomonas acinetobacter enhydrobacter staphylococcus unassigned corynebacterium micrococcus haemophilus [prevotella] neisseria klebsielle granulicatella veillonella rothia prevotella porphyromonas actinomyces peptoniphilus pseudomonas paracoccus leptotrichia chryseobacterium kocuria lactococcus anaerococcus unclassified finegoldia unassigned streptococcus xanthomonas acinebacter enhydrobacter staphylococcus corynebacterium micrococcus haemophilus [prevotella] neissera klebsiella granulicatella veillonella rothia prevotella porphyromonas actinomyces peptoniphilus pseudomonas paracoccus leptotrichia chryseobacterium kocuria lactococcus anaerococcus uniclassified finegoldia average taxonomic composition (30 main genus) of the skin microbiome associated with ad prior (a) and post (b) balneotherapy associated with unaffected (uaf) and affected (af) for gram-negative bacteria, wilcoxon rank sum test with continuity correction (w = 163.5, p-value = 0.06711) and for gram-positive bacteria wilcoxon rank sum test with continuity correction (w = 320, p-value = 0.06887). relative abundance of gram-negative (a) and gram-positive (b) bacteria at the surface of affected and unaffected skin of patients affected by atopic dermatitis prior (d0) and post (d21) balneotherapy reads reads fc17posterlarochemoyalskinmicrobiota.pdf powerpoint presentation how mohs surgeons utilize prognostic testing for high-risk cutaneous squamous cell carcinoma (scc): a clinical impact study › jjs, sjk, alf, ap, br are employees and shareholders of castle biosciences, inc. › sta is a consultant for castle biosciences, inc. sarah t. arron, md, phd1; alison l. fitzgerald, phd2; jennifer j. siegel, phd2; anesh prasai, phd2; briana rackley, phd2; sarah j. kurley, phd2; brent moody, md3 1peninsula dermatology, burlingame, ca, usa; 2castle biosciences, inc., friendswood, tx, usa; 3skin cancer surgery center, nashville, tn for more information: skurley@castlebiosciences.com ›97% of mohs surgeons in this study are familiar with or use the 40gep test for high-risk scc patients. ›study results determined that clinicopathologic risk factors most likely to cause metastasis are also ones that would prompt usage of the personalized molecular information provided by the 40-gep. ›40-gep results guide mohs surgeons to make risk-aligned management plans and increase their confidence in these decisions. ›overall, the 40-gep can focus treatment options in the most riskappropriate manner, allowing for an optimization of healthcare resources and improved patient outcomes. conclusions › an anonymous survey was distributed to current american college of mohs surgery (acms) members. the study consisted of demographic questions, familiarity with and use of nccn guidelines, ajcc-8 staging, bwh staging, and the 40-gep. › participants (n=39) were provided with background on the validation of the 40-gep test, then evaluated the use of risk factors for the assessment of scc patients within their practice and which were concerning enough to warrant the use of the 40-gep. › participants were presented with a high-risk scc patient vignette and asked for their risk assessment and treatment approaches preand post-40-gep results. presented at fall clinical dermatology conference, october 20-23, 2022, las vegas nv disclosures › as mohs surgeons are a clinical specialty likely to see high-risk scc patients frequently, a clinical impact study was performed to determine how patient management decisions are impacted by their use of the 40-gep test. figure 1. performance of the 40-gep to stratify patients by risk of regional or distant metastasis from scc synopsis objective methods results references › of the 1.8 million annually diagnosed scc cases, more than 95% are cured by surgery; however, an average of 5% progress to metastasis, with up to 2.1% dying from the disease.1-3 › a scc patient’s likelihood for poor outcomes governs management decisions regarding a multitude of treatment modalities. › the 40-gene expression profile (40-gep) test has been validated to stratify primary scc patients having one or more clinicopathologic risk factors into three biological risk groups (low = class 1; moderate = class 2a; high = class 2b) based on risk for regional, nodal, or distant metastasis (figure 1). 4,5 › clinical validity studies have shown an improvement to risk stratification of high-risk scc patients when compared to staging systems. 4,5 › when 40-gep test results are incorporated into a clinician’s initial risk assessment, clinical utility studies have demonstrated the ability of the test to personalize patient management plans in a risk-aligned manner. 5-9 › demographics of the n=39 mohs surgeons who participated in the study are shown in table 1. the distribution of study participants usage of national comprehensive cancer network (nccn) guidelines and staging systems for risk assessment, along with their familiarity with gep testing for scc are shown in figure 2. results table 1. demographics of study participants little or no low somewhat confident very baseline class 1 class 2a class 2bc o n fid e n ce le ve l 0% 20% 40% 60% 80% 100% follow-up baseline (pre-gep) class 1 class 2a class 2b c lin ic ia ns r es po ns e 5-12x per year3-4x per year1-2x per year follow-up 1-2x per year 3-4x per year 5-12x per year c lin ic ia n r e sp o n se 0% 20% 40% 60% 80% 100% adjuvant radiation therapy baseline(pre-gep) class 1 class 2a class 2b c lin ic ia ns r es po ns e recommen d conside r avoid c lin ic ia n r e sp o n se adjuvant radiation therapy avoid consider recommend 0% 20% 40% 60% 80% 100% nodal imaging baseline(pre-gep) class 1 class 2a class 2b c lin ic ia ns r es po ns e recommen d conside r avoid nodal imaging avoid consider recommend c lin ic ia n r e sp o n se 0% 20% 40% 60% 80% 100% c lin ic ia ns r es po ns e class 1 class 2a class 2b baseline (pre-gep) low intensity moderate intensity high intensity overall management intensity c lin ic ia n r e sp o n se low intensity moderate intensity high intensity management intensity figure 2. summary of study participants preferred methods of risk assessment and familiarity with gep years in practice (%) 1-10 years 46 11-20 years 38 21-30 years 8 >30 years 8 table 2. utilization of the 40-gep by study participants aligns with nccn very and high-risk factors * indicates nccn defined very high-risk factor › table 2 displays the highest-ranking risk factors (on a scale of 1-5) most likely to cause metastasis as decided on by study participants. factors that participants rank as most concerning are also the factors they feel would most likely benefit from the prognostic information provided by the 40-gep. › study participants were presented with a high-risk scc patient vignette (figure 3). responses to treatment modalities demonstrated increases in elevation of management when class results indicated an increased risk of metastasis. › overall confidence in decision making increased when integrating 40-gep test results (figure 4) institution (%) academic center 33 multi-specialty group 25 other private practice 36 hospital based 5 other 0 institution (%) academic center 33 multi-specialty group 25 other private practice 36 hospital based 5 other 0 following nccn guidelines always often sometimes rarely never staging system used ajcc8* bwh** both i assess patients with risk factors only familiarity with gep testing for scc not familiar somewhat familiar very familiar i have used a gep test for scc patient vignette › 68-year-old male › 2.6 diameter lesion on left temple › biopsy confirmed scc › infiltrating subtype › poor differentiation figure 3. risk aligned treatment decision are made when 40-gep test results are integrated into patient management figure 4. confidence in patient management decisions increased with use of 40-gep * american joint committee on cancer staging manual, 8th edition; **brigham and women’s hospital staging system 1. rogers et al. jama derm. 2015 4. wysong, et al. j am acad dermatol. 2021 7. litchman, et al. cmro. 2020 2. skincancer.org, skin cancer foundation 5. ibrahim, et al. future oncol. 2021 8. arron, et al. j drugs dermatol. 2022 3. schmults et al. jama derm 2013 6. teplitz, et al. j drugs dermatol. 2019 9. hooper, et al. cancer invest. 2022 baseline (pre-gep) class 1 class 2a class 2b 42% of mohs surgeons reported increased confidence in management decisions with 40-gep testing scan here for more info https://castlebiosciences.com/research-development/publications/ slide number 1 skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 354 skimages hypopigmented patches on the trunk of a 25-year-old hispanic male mckenzie a. dirr, ba, bs1, nicholas brownstone, md2, darrell rigel, md, ms3 1 medical university of south carolina, charleston, sc 2 national society for cutaneous medicine, new york, ny 3 department of dermatology, mount sinai icahn school of medicine, new york, ny we present a case in which a 25-year-old hispanic male presented to clinic with asymptomatic patches of hypopigmented skin on the arm and back. he first noticed the lesions two weeks prior, with no previous history of similar complaints. upon clinical inspection, he was found to have tinea versicolor (tv) and treatment was promptly initiated. this demonstrates a case of hypopigmented tv in a patient with fitzpatrick skin type iv, and illustrates an example of one of the many forms in which tv may present. tinea versicolor, or pityriasis versicolor, is a pathologic fungal colonization of the stratum corneum.1,2,3 caused by malassezia, a fungal genus that is normally found on the skin, tv skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 355 pathologically overgrows in warm, humid conditions. 1,2,3 tv is lipophilic and is commonly found in anatomic locations with increased density of sebaceous glands, such as the arms, trunk, neck, and face.1,2,3 while tv does not damage the underlying skin or cause long-term morbidity or mortality, it can present a frustrating cosmetic challenge for patients.1 tv can have a varied presentation, including multicolored, well-demarcated lesions of hypopigmentation, hyperpigmentation, and erythematous macules that may scale, itch, or present asymptomatically. 1,2 the etiology of hypopigmentation is multifactorial, including malassezia-induced reduction of melanosome size, invasion of keratinocytes which ultimately damages melanocytes and blocks formation of melanin, and blockade of uv light, causing unevenness in pigmentation.1,3 inflammatory reactions and enlargement of melanosomes can lead to hyperpigmentation.1,2,3 the varied presentation can lead to a delay in diagnosis, and as such, it is import to differentiate how tv may present in patients of different fitzpatrick skin types. it had previously been proposed that in patients with skin of color, hypopigmentation is more common, with the potential to combine into a larger, amalgamated area of discoloration, while patients with lighter skin tones are more likely to present with hyperpigmentation. 1,4 however, in a study done by aljabre et. al, this claim was not supported, with the authors finding that patients with skin of color are likely to present with any tv variation, including macules of dark brown or grayblack hyperpigmentation.1,2,4 further publications have also supported the finding that patients with skin of color are likely to develop any tv variation, and thus it is important for physicians to have an increased understanding of all of the possible tv presentations.2 the diagnosis of tv can be made clinically, with biopsy, using wood’s light, or via koh prep and direct visualization under light microscopy, where it is visualized as nonbranching pseudohyphae with circular spores. 1,2,3 management of tv in patients should take into account patient preference and disease course, as a topical antifungal is sufficient in most cases. 1,2 however, in severe or persistent infections, oral antifungals may be the more effective solution.1,2 it is important to note the increased risk of post-inflammatory hyper/hypopigmentation seen in patients with skin of color, which may warrant an aggressive treatment approach, while simultaneously weighing the potential side effects of oral medication.1,2 conflict of interest disclosures: none funding: none corresponding author: mckenzie a. dirr, ba, bs medical university of south carolina 96 jonathan lucas street suite 601, msc 617 charleston, sc 29425 phone: 843-792-2081 email: dirr@musc.edu references: 1. vashi na, maibach hi. dermatoanthropology of ethnic skin and hair. 1st ed. 2017. (vashi na, maibach hi, eds.). springer international publishing; 2017. doi:10.1007/978-3-319-539614 2. kallini jr, riaz f, khachemoune a. tinea versicolor in dark-skinned individuals. international journal of dermatology. 2014;53(2):137-141. doi:10.1111/ijd.12345 3. schwartz ra. superficial fungal infections. lancet. 2004;364(9440):1173–82. 4. aljabre sh, et al. pigmentary changes of tinea versicolor in dark-skinned patients. int j dermatol. 2001;40(4):273–5. mailto:dirr@musc.edu skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 356 skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 387 research letter seasonal trends of ambulatory visit burden in hidradenitis suppurativa patients terri shih, bs1*, devea r de, bs2*, jonathan rick, md3, vivian y shi, md3, jennifer l hsiao, md4 *both authors contributed equally to this work 1 david geffen school of medicine, university of california los angeles, los angeles, ca 2 university at buffalo, jacobs school of medicine and biomedical sciences, buffalo, ny 3 department of dermatology, university of arkansas for medical sciences, little rock, ar 4 department of dermatology, university of southern california, los angeles, ca hidradenitis suppurativa (hs) is a chronic, debilitating inflammatory skin condition characterized by painful nodules, abscesses, and tunnels often in intertriginous areas. patients with hs have reported exacerbation of hs with heat, friction, and sweating,1 particularly in warmer climates. despite this, the seasonal trends of the ambulatory visit burden due to hs have not been well characterized. herein, we examine the seasonal burden of ambulatory visits due to hs in the united states. abstract introduction: patients with hidradenitis suppurativa (hs) report hs flares with increased heat and sweat. however, there is a paucity of literature on whether there is an increased ambulatory visit burden for hs patients during the warmer months. methods: we used a nationally representative database of ambulatory visits in the united states, the national ambulatory medical care survey to examine the seasonal trends of ambulatory visits for patients with hs. data analyses were performed using sas studio 9.04.01 (sas institute, cary, n.c., usa), and variance in the complex survey design is accounted for by utilizing survey weights to create national estimates and confidence intervals. results: we identified approximately 2.33 million outpatient visits (95% confidence interval 1.95 million-2.71 million) between 2008-2018 with a diagnosis of hs. approximately 21% of visits occurred during winter to early spring (january to april), 51% during late spring to summer (may to august), and 28% during autumn (september to december). the number of visits differed significantly between these three time periods (x2=13.1, p=0.0014). conclusion: awareness of the increased burden of hs during summer months may help guide management, including anticipatory counseling on strategic lifestyle modifications and initiation of anti-hyperhidrosis treatments. introduction skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 388 the national ambulatory medical care survey (namcs) is conducted annually by the national center for health statistics (nchs), which utilizes a stratified, random sample of patient visits to nonfederal, ambulatory office-based physicians. we searched publicly available namcs data between 2008 to 2018 for visits with a diagnosis of hs (icd-9 code 705.83, icd-10 code l73.2). descriptive statistics were completed for visit demographics and characteristics. chi-squared tests and multivariate logistic regressions analyzed trends visits while controlling for race, sex, and age. all data analyses were performed using sas studio 9.04.01 (sas institute, cary, n.c., usa). variance in the complex survey design is accounted for by utilizing survey weights to create national estimates methods table 1. survey-weighted visit demographics and characteristics of hidradenitis suppurativa visits skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 389 and confidence intervals. from the 2008-2018 namcs datasets, approximately 2.33 million visits (95% confidence interval 1.95 million-2.71 million) had a diagnosis of hs. of these visits, 71.1% of patients were female, 75.6% were white, and the mean age was 37.9 ± 1.0 (table 1). visit frequency were highest in the months of may (14.0%, ci 9.6%-18.5%), june (14.3%, ci 5.3%-23.3%), and july (14.2%, ci 2.0%-26.5%), and lowest in january (4.9%, ci 0.0%-10.9%), february (5.1%, ci 2.0%-8.2%), and november (2.8%, ci 0.3%5.3%) (figure 1). approximately a fifth of visits occurred from winter to early spring (january to april, 21.1%, ci 13.3-28.9%), approximately half from late spring to summer (may to august, 51.2%, ci 40.162.3%), and the remainder from autumn (september to december (27.7%, ci 16.638.7%). the number of visits were significantly different between these three time periods (x2=13.1, p=0.0014). multivariate analyses identified no significant differences in visit number during these months based on gender, race, region, insurance status, and whether the provider was a dermatologist. results discussion figure 1. survey-weighted number of hs visits per 100.000 visits by month skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 390 this nationally representative cohort highlights the increased ambulatory burden of patients with hs during the months of may to august. this parallel the higher burden of national emergency department visits due to hs in the summer.2 the temporal patterns may be due to increased hyperhidrosis and friction during warmer climates, both identified by patients as exacerbating factors of hs that impair quality of life.3 patients report sweating, heat, and exercise to be common aggravating hs factors.4 seasonal aggravation has also been described for other skin conditions such as acne.5 anticipation of seasonal disease burden and changes in management, such as initiating or adjusting dosing of anti-hyperhidrosis medications,6 may help improve disease control. a systematic review of antihyperhidrosis treatments in hs have identified botulinum toxin to improve disease in some hs patients, with or without concomitant hyperhidrosis. clinicians may also counsel patients on measures to keep cool and minimize friction. ensuring continued monitoring of the mental and emotional well-being of patients during the warmer months where flares may be more frequent is also important. limitations of namcs include the lack of data on long-term continuity of care and severity of hs disease. the number of hs ambulatory visits may be underrepresented overall given frequent misdiagnoses or delayed diagnoses. our findings can help dermatologists anticipate a higher burden of hs management during late spring and summer months to help ensure continued access to care and address potential season-related hs triggers such as hyperhidrosis early. conflict of interest disclosures: jlh is on the board of directors for the hidradenitis suppurativa foundation, has served as a consultant for boehringer ingelheim, novartis, and ucb, and has served as a consultant and speaker for abbvie. vys is on the board of directors for the hidradenitis suppurativa foundation (hsf), is a stock shareholder of learn health and has served as an advisory board member, investigator, speaker, and/or received research funding from sanofi genzyme, regeneron, abbvie, eli lilly, novartis, sun pharma, leo pharma, pfizer, incyte, boehringer-ingelheim, aristea therapeutics, menlo therapeutics, dermira, burt’s bees, galderma, kiniksa, ucb, webmd, target-pharmasolutions, altus lab, myor, polyfin, gpskin and skin actives scientific. there was no financial transaction for the preparation of this manuscript. all other authors report no conflicts of interest. funding: none corresponding author: jennifer l. hsiao, md department of dermatology university of southern california 1441 eastlake ave, ezralow tower, suite 5301 los angeles, ca 90033 phone: (310) 601-3367 email: j.hsiao.publications@gmail.com references: 1. shih t, lee k, seivright jr, de dr, shi vy, hsiao jl. hyperhidrosis treatments in hidradenitis suppurativa: a systematic review. dermatologic therapy. n/a(n/a):e15210. doi:10.1111/dth.15210 2. tripathi r, korman nj, ezaldein hh. seasonal burden of national emergency department visits due to hidradenitis suppurativa. j am acad dermatol. 2022;86(6):1362-1365. doi:10.1016/j.jaad.2021.05.023 3. alikhan a, sayed c, alavi a, et al. north american clinical management guidelines for hidradenitis suppurativa: a publication from the united states and canadian hidradenitis suppurativa foundations: part i: diagnosis, evaluation, and the use of complementary and procedural management. j am acad dermatol. 2019;81(1):76-90. doi:10.1016/j.jaad.2019.02.067 4. thompson am, fernandez jm, rick j, et al. identifying triggers for hidradenitis suppurativa flare: a patient survey. br j skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 391 dermatol. 2021;185(1):225-226. doi:10.1111/bjd.19926 5. narang i, sardana k, bajpai r, garg vk. seasonal aggravation of acne in summers and the effect of temperature and humidity in a study in a tropical setting. j cosmet dermatol. 2019;18(4):1098-1104. doi:10.1111/jocd.12777 6. del boz j, millán-cayetano jf, garcíamontero p, garcía-harana c, rivas-ruiz f, de troya-martín m. adjusting oral oxybutynin medication for hyperhidrosis to reflect seasonal temperature variations. dermatol ther. 2018;31(4):e12615. doi:10.1111/dth.12615 objectives to evaluate the long-term maintenance of psoriasis area and severity index (pasi) ≤2 and pasi=0 responses with bimekizumab (bkz), using the largest available two-year data pool, in patients with moderate to severe plaque psoriasis. introduction • long-term treatment efficacy is an important consideration in chronic diseases such as psoriasis. • bkz has demonstrated high levels of skin clearance for the treatment of moderate to severe plaque psoriasis in phase 3/3b clinical trials.1–4 methods • data were pooled from the be sure, be vivid and be ready phase 3 trials, the be bright open-label extension (ole), and be radiant (48-week double-blinded phase 3b trial and ongoing ole).1–5 • patients included in these analyses were randomized at baseline to bkz 320 mg every four weeks (q4w) to week 16, followed by bkz q4w or every eight weeks (q8w) maintenance dosing for the remainder of the double-blinded period of the trials (figure 1). • upon ole entry, patients received bkz 320 mg q4w or q8w based on pasi (psoriasis area and severity index) response at the end of the feeder studies (figure 1). • we report the proportion of patients achieving pasi ≤2 and pasi=0 through two years of treatment (ole week 48) among bkz-randomized week 16 pasi ≤2 and pasi=0 responders, who remained on the same bkz maintenance dose upon entering the relevant ole (q4w/q8w/q8w or q4w/q4w/q4w). • missing data were imputed using non-responder imputation (nri), modified nri (mnri), and observed case (oc). – for mnri, patients who discontinued treatment due to lack of efficacy were considered non-responders; multiple imputation was used for all other missing data. results • baseline characteristics of week 16 pasi ≤2 and pasi=0 responders who entered be bright or the be radiant ole are reported in table 1. • at week 16, 87.1% of the 1,362 patients randomized to bkz 320 mg q4w at baseline of the feeder studies achieved pasi ≤2 (nri; figure 2a) and 62.4% achieved pasi=0 (nri; figure 2b). • among week 16 pasi ≤2 responders who entered the oles, 96.3% of the 349 patients on q4w/q8w/q8w and 95.1% of the 449 patients on q4w/q4w/q4w maintained pasi ≤2 through two years (ole week 48) (mnri; figure 2a). • of the week 16 pasi=0 responders who entered the oles, 83.8% of the 267 patients on q4w/q8w/q8w and 85.1% of the 316 patients on q4w/q4w/q4w maintained pasi=0 through two years (ole week 48) (mnri; figure 2b). summary presented at the 42nd annual fall clinical dermatology conference | las vegas, nv | october 20–23, 2022 conclusions a high proportion of patients who achieved complete or near complete skin clearance at week 16 maintained their response through two years, regardless of bkz maintenance dosing regimen (q4w/q8w/q8w or q4w/q4w/q4w). d. thaçi,1 a. armstrong,2 m. lebwohl,3 a. blauvelt,4 c. paul,5 l. puig,6 m. wang,7 v. vanvoorden,8 c. madden,7 s. wiegratz,9 d. deherder,10 k.b. gordon11 maintenance of bimekizumab efficacy through 2 years in patients with moderate to severe plaque psoriasis: pooled results from five phase 3/3b trials previously presented at spin 2022 institutions: 1institute and comprehensive center for inflammation medicine, university of lübeck, lübeck, germany; 2keck school of medicine of usc, dermatology, los angeles, california, usa; 3icahn school of medicine at mount sinai, new york, new york, usa; 4oregon medical research center, portland, oregon, usa; 5toulouse university and chu, toulouse, france; 6hospital de la santa creu i sant pau, universitat autònoma de barcelona, barcelona, spain; 7ucb pharma, raleigh, north carolina, usa; 8ucb pharma, brussels, belgium; 9ucb pharma, monheim, germany; 10ucb pharma, braine-l’alleud, belgium; 11medical college of wisconsin, milwaukee, wisconsin, usa. references: 1warren rb et al. n engl j med 2021;385:130–141, nct03412747; 2reich k et al. lancet 2021;397:487–498, nct03370133; 3gordon kb et al. lancet 2021;397:475–486, nct03410992; 4reich k et al. n engl j med 2021;385:142–152, nct03536884; 5be bright: nct03598790. author contributions: substantial contributions to study conception/design, or acquisition/analysis/ interpretation of data: dt, aa, ml, ab, cp, lp, mw, vv, cm, sw, dd, kbg; drafting of the publication, or revising it critically for important intellectual content: dt, aa, ml, ab, cp, lp, mw, vv, cm, sw, dd, kbg; final approval of the publication: dt, aa, ml, ab, cp, lp, mw, vv, cm, sw, dd, kbg. author disclosures: dt: honoraria for participation on advisory boards, as a speaker, and for consultancy from abbvie, almirall, amgen, biogen, boehringer ingelheim, bms, celltrion, eli lilly, galapagos, janssen, leo pharma, novartis, pfizer, regeneron, samsung, sanofi genzyme, and ucb pharma; research grants received from leo pharma and novartis. aa: has served as a research investigator and/or scientific advisor to abbvie, almirall, arcutis, aslan, boehringer ingelheim, bristol myers squibb, dermavant, dermira, eli lilly, epi, incyte, janssen, leo pharma, nimbus, novartis, ortho dermatologics, pfizer, regeneron, sun pharma, sanofi, and ucb pharma. ml: employee of mount sinai and receives research funds from abbvie, amgen, arcutis, avotres, boehringer ingelheim, dermavant, eli lilly, incyte, janssen, ortho dermatologics, regeneron, and ucb pharma; consultant for aditum bio, almirall, altrubio, anaptysbio, arcutis, aristea therapeutics, arrive technologies, avotres therapeutics, biomx, boehringer ingelheim, bristol myers squibb, cara therapeutics, castle biosciences, corrona, dermavant sciences, dr. reddy’s laboratories, evelo biosciences, evommune, facilitation of international dermatology education, forte biosciences, foundation for research and education in dermatology, helsinn therapeutics, hexima, leo pharma, meiji seika pharma, mindera, pfizer, seanergy, and verrica. ab: has served as a speaker (received honoraria) for abbvie, arcutis, bristol myers squibb, eli lilly, pfizer, regeneron, sanofi, and ucb pharma, served as a scientific adviser (received honoraria) for abbvie, abcentra, affibody, aligos, almirall, alumis, amgen, anaptysbio, arcutis, arena, aslan, athenex, bluefin biomedicine, boehringer ingelheim, bristol myers squibb, cara therapeutics, dermavant, ecor1, eli lilly, escient, evelo, evommune, forte, galderma, highlightii pharma, incyte, innoventbio, janssen, landos, leo pharma, merck, novartis, pfizer, rapt, regeneron, sanofi genzyme, spherix global insights, sun pharma, tll pharmaceutical, trialspark, ucb pharma, vibliome, and xencor, and has acted as a clinical study investigator (institution has received clinical study funds) for abbvie, acelyrin, almirall, amgen, arcutis, athenex, boehringer ingelheim, bristol myers squibb, concert, dermavant, eli lilly , evelo, evommune, galderma, incyte, janssen, leo, merck, novartis, pfizer, regeneron, sun pharma, and ucb pharma. cp: consulting fees and/or grants from abbvie, almirall, amgen, boehringer ingelheim, celgene, gsk, janssen cilag, leo pharma, eli lilly, novartis, pierre fabre, pfizer, sanofi regeneron, and ucb pharma. lp: received consultancy/speaker’s honoraria from and/or participated in trials sponsored by abbvie, almirall, amgen, baxalta, biogen, boehringer ingelheim, celgene, eli lilly, gebro, janssen, js biocad, leo pharma, merck-serono, msd, mylan, novartis, pfizer, regeneron, roche, samsung-bioepis, sandoz, sanofi genzyme, and ucb pharma. mw, vv, cm, sw, dd: employees and shareholders of ucb pharma. kbg: has received consulting fees from abbvie, almirall, amgen, boehringer ingelheim, bms, celgene, dermira, eli lilly, janssen, novartis, pfizer, sun pharma, and ucb pharma; research support from abbvie, bms, celgene, eli lilly, janssen, novartis, and ucb pharma. acknowledgments: this study was funded by ucb pharma. we thank the patients and their caregivers in addition to the investigators and their teams who contributed to this study. the authors acknowledge natalie nunez gomez, md, ucb pharma, monheim, germany, for critical review, yasha najafi, msc, costello medical, london, uk, for medical writing and editorial assistance, and the costello medical design team, uk for graphic design assistance. all costs associated with development of this poster were funded by ucb pharma. table 1 baseline characteristics: bkz-randomized week 16 responders bkz: bimekizumab; bsa: body surface area; dlqi: dermatology life quality index; iga: investigator’s global assessment; mnri: modified non responder imputation; nri: non-responder imputation; oc: observed case; ole: open-label extension; pasi: psoriasis area and severity index; pasi 90: ≥90% improvement from baseline in pasi; q4w: every four weeks; q8w: every eight weeks; sd: standard deviation; wk: week. a) pasi ≤2 figure 1 study design: included patients figure 2 maintenance of pasi response through two years in bkz-randomized week 16 responders (pooled; mnri, nri, oc) b) pasi=0 pasi ≤2 responders (n=994) pasi=0 responders (n=719) age (years), mean ± sd 45.0 ± 13.5 45.1 ± 13.3 male, n (%) 689 (69.3) 497 (69.1) caucasian, n (%) 871 (87.6) 642 (89.3) weight (kg), mean ± sd 88.9 ± 20.7 87.9 ± 19.6 duration of psoriasis (years), mean ± sd 18.2 ± 12.6 18.2 ± 12.6 pasi, mean ± sd 20.8 ± 7.5 20.8 ± 7.3 bsa (%), mean ± sd 26.3 ± 15.5 25.8 ± 15.0 iga, n (%) 3: moderate 661 (66.5) 476 (66.2) 4: severe 330 (33.2) 242 (33.7) dlqi, mean ± sd 10.7 ± 6.4 10.9 ± 6.5 any prior systemic therapy, n (%) 768 (77.3) 568 (79.0) prior biologic therapy, n (%)a 382 (38.4) 282 (39.2) all bkz-treated patients received bkz 320 mg q4w through week 16. data are reported for all patients with a response at week 16 who enrolled in be bright or the be radiant ole, regardless of dosing regimen. apatients with multiple prior biologic use included in n (%). bkz 320 mg q4w ole week 48 week 96 week 100/104 ole week 16/24d week 64 week 76/80 ole week 0b week 48 week 52/56c be radiant be brighta week 16 response assessment initial treatment period maintenance period open-label treatment period be sure, be vivid, be ready, and be radiant1–4 (pooled, double-blind) bkz 320 mg q8w be bright and be radiant5 (open-label extension) bkz 320 mg q4w n=1,362 <pasi 90 bkz 320 mg q4w bkz 320 mg q8w ≥pasi 90 <pasi 90 ≥pasi 90 bkz 320 mg q8w bkz 320 mg q4w 4:1 be bright 1:1 be radiant p ro p o rt io n o f p a ti e n ts a c h ie v in g p a s i ≤ 2 ( % ) 100 80 60 40 20 0 16 20 24 28 32 36 40 44 48c ole wk4 ole wk8 ole wk12 ole wk16 ole wk20 ole wk24 ole wk28 ole wk32 ole wk36 ole wk40 ole wk44 ole wk48 97.5% 96.3% 89.7% bkz 320 mg q4w/q8w/q8w (n=349)b double-blinded treatment open-label extension week mnri nri oc p ro p o rt io n o f p a ti e n ts a c h ie v in g p a s i ≤ 2 ( % ) 100 80 60 40 20 0 16 20 24 28 32 36 40 44 48c ole wk4 ole wk8 ole wk12 ole wk16 ole wk20 ole wk24 ole wk28 ole wk32 ole wk36 ole wk40 ole wk44 ole wk48 96.4% 88.9% 95.1% bkz 320 mg q4w/q4w/q4w (n=449)b double-blinded treatment open-label extension week mnri nri oc week 16: 87.1% (1,186/1,362) of bkz‐treated patients achieved pasi ≤2 during the initial period (nri)a bkz 320 mg q4w (n=1,362) 87.1% p ro p o rt io n o f p a ti e n ts a c h ie v in g p a s i= 0 ( % ) 100 80 60 40 20 0 16 20 24 28 32 36 40 44 48c ole wk4 ole wk8 ole wk12 ole wk16 ole wk20 ole wk24 ole wk28 ole wk32 ole wk36 ole wk40 ole wk44 ole wk48 88.2% 83.8% 81.3% bkz 320 mg q4w/q8w/q8w (n=267)b double-blinded treatment open-label extension week mnri nri oc p ro p o rt io n o f p a ti e n ts a c h ie v in g p a s i= 0 ( % ) 100 80 60 40 20 0 16 20 24 28 32 36 40 44 48c ole wk4 ole wk8 ole wk12 ole wk16 ole wk20 ole wk24 ole wk28 ole wk32 ole wk36 ole wk40 ole wk44 ole wk48 87.5% 81.3% bkz 320 mg q4w/q4w/q4w (n=316)b double-blinded treatment open-label extension week mnri nri oc week 16: 62.4% (850/1,362) of bkz‐treated patients achieved pasi=0 during the initial period (nri)a bkz 320 mg q4w (n=1,362) 62.4% 85.1% the vast majority of bkz-randomized patients with complete/near-complete skin clearance at week 16 maintained their response through two years maintenance of pasi ≤2 response in week 16 responders after two years (ole week 48; mnri) maintenance of pasi=0 response in week 16 responders after two years (ole week 48; mnri) 96.3% 95.1% 83.8% 85.1% q4w/q8w/q8w (n=349) q4w/q4w/q4w (n=449) q4w/q8w/q8w (n=267) q4w/q4w/q4w (n=316) aweek numbers are based on feeder study baseline; bpatients who achieved ≥pasi 90 at week 48 were randomized 4:1 in be bright and 1:1 in be radiant to receive bkz 320 mg q4w or bkz 320 mg q8w; cbe vivid week 52, and be sure and be ready weeks 52 and 56 were not included in the pooled analysis; ddose switch: in be bright, at ole week 24, patients who achieved ≥pasi 90 switched to q8w dosing at the investigator’s discretion; in be radiant, at ole week 16 or the next scheduled visit, dose switches were added via a protocol amendment. aresponse at week 16 in patients randomized to bkz 320 mg q4w at baseline (nri); bdata reported for patients with a response at week 16 who received continuous maintenance dosing regimens; cthe be sure and be ready feeder studies ran for 56 weeks, be vivid ran for 52 weeks, and be radiant ran for 48 weeks; to pool data across all four studies, feeder study data from weeks 52–56 were not included. skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 594 brief article late onset pseudolymphomatous reaction to blue tattoo pigment precipitated by covid vaccination malvika ramesh, bs1, landon hope, md1, clay cockerell, md2, richard hope, md3 1texas tech university school of medicine, lubbock, tx 2cockrell dermatopathology, dallas, tx 3texas tech university department of dermatology, lubbock, tx pseudolymphoma has been reported to occur as a complication of tattoos and is marked by tissue histology that may simulate cutaneous b-cell lymphoma most commonly.1,2 the process is benign and can be differentiated by demonstrating polyclonality of lymphocytes versus the monoclonality seen in malignant processes.3,4 it has been hypothesized that particles in tattoo pigments, commonly red pigment, serve as dermal antigens and induce lymphoid cell proliferation.5 this leads to a persistent reactive lymphocytic infiltration seen usually resulting in the development of germinal centers. the exact mechanism of the pathogenesis of the pseudolymphoma has yet to be defined, however.5,6 in some cases, some factor leads to activation of the immune system resulting in a hyperactive local immune response leading to a pseudolymphomatous reaction in the skin such as exaggerated arthropod assault reactions. this has been observed in patients with hematologic malignant neoplasms and other immunodeficiency states such as hiv infection.7-10 we herein report a patient who developed a pseudolymphomatous tattoo reaction in a long-standing blue tattoo that abstract tattoos can lead to a variety of cutaneous conditions such as allergic or contact dermatitis, lichenoid dermatitis, pseudolymphomatous reactions and granulomatous responses such as foreign body granulomas that may have a sarcoidal histology simulating sarcoidosis. pseudolymphomatous reactions are less common and may clinically and histologically resemble cutaneous lymphomas. pseudolymphomatous reactions may develop in response to injections, borrelia infections and arthropod bites. diagnosis of cutaneous pseudolymphoma is usually based on clinicopathologic correlation coupled with skin biopsy and ancillary tests such as immunoperoxidase stains and genetic testing when necessary. treatment is generally successful with application of topical corticosteroid preparation or injection of intralesional corticosteroids and in some cases, surgical excision. here, we describe the case of a 61-year-old male who presented with 3-4 mm papules contained within the blue region of a multicolored tattoo on his upper right arm that had been present for several years. the reaction developed shortly following a covid vaccination. introduction skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 595 developed shortly after receiving a vaccination for covid-19. a 61-year-old male with past medical history of type 2 diabetes mellitus, hypertension, hypercholesterolemia, and hypertriglyceridemia presented to an outpatient private practice dermatologist with a chief complaint of papules in a tattoo. the papules occurred only in the blue ink in the tattoo of his right upper arm and developed approximately one year previously after a recent moderna bivalent mrna-1273 covid vaccination (figure 1). the papules were found nowhere else on his body and began 3-4 weeks after receiving the second of both doses of the moderna covid-19 vaccine. the tattoo was 5-6 years old, and the papules spread along the blue ink of the tattoo only (figure 2). they were slightly pruritic. the patient had not used any topical or systemic therapies prior to evaluation. the patient reported no reactions or problems with the original tattoo. figure 1. pseudolymphomatous reaction to tattoo large multicolored tattoo with various sized granulomatous-appearing papules. figure 2. papules confined to blue ink the papules were not found anywhere else in the tattoo, specifically the red or black pigment nearby. on exam, the eruption was contained within the blue portion a large multicolored tattoo with various sized pink to skin-colored papules. punch biopsy demonstrated a dense inflammatory cell infiltrate in the upper dermis composed of lymphocytes, histiocytes, eosinophils and plasma cells most consistent with a pseudolymphomatous tattoo reaction (figure 3). the patient was treated with a class one topical steroid cream and injection of intralesional steroids which resulted in improvement but not disappearance of the lesions. in pseudolymphomatous reactions, the tattoo dye pigments in the dermis act as an antigen stimulating the polyclonal proliferation of lymphoid cells.3,5,6 the onset can range from a few months to several years after the tattoo placement.3,5,6 while most cases have been case report discussion skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 596 figure 3. dense inflammatory infiltrate composed of a mix of lymphocytes, histiocytes, and plasma cells. infiltrate is distributed as prominent band in the upper dermis (left) and in perifollicular and peri-eccrine locations in the deeper dermis (right). described following red tattoos in patients with delayed sensitivity to cinnabar (mercuric sulfate), inflammatory reactions can also occur in blue areas, which are mainly cobalt salts, or green areas which are mainly chrome salts.2,4-7 here, the covid vaccination and booster coincided with the appearance of the pseudolymphoma and likely served as a stimulus for its development possibly via a hyperactive immune response.5,6,10 exposure to the covid 19 spike protein, through vaccination or infection, has been associated with cases of delayed inflammatory reactions in hyaluronic acid dermal fillers.11 it’s suggested that the spike protein interaction with dermal ace2 receptors favors a pro-inflammatory, locoregional th1 cascade, promoting a cd8+t cell mediated reaction to incipient granulomas, which previously formed around residual ha particles.10,11 this reaction resembles our case with a delayed inflammatory reaction post covid vaccination. further, a study found an increase in autoimmunity and immune response following infection with covid-19 due to molecular mimicry between human tissue and viral antigens.12 thus, in our patient covid vaccination may have triggered the inflammatory immune response to tattoo dye. although pseudolymphoma is a benign disease, in cases which are persistent, prolonged follow up is important because of rare case reports of progression to cutaneous lymphoma.8 tattoo pseudolymphoma can be treated with topical or intralesional corticosteroids, surgical excision, or laser treatment.7 in our patient, conservative treatment with topical and intralesional steroids resulted in resolution. allergic reactions may develop in patients with tattoos that may assume several different morphologies, both clinically and histologically. while these may develop spontaneously, covid-19 vaccination may be a stimulus that leads to development of cutaneous inflammatory disorders in tattoos that were previously well-tolerated. clinicians should be aware of this rare conclusion skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 597 phenomenon which should be added to the list of cutaneous reactions that can follow covid-19 vaccination. conflict of interest disclosures: none funding: none corresponding author: malvika ramesh, bs texas tech university school of medicine 3601 4th st. lubbock, tx 79430 email: malvika.ramesh@hotmail.com references: 1. pasolini g, ghidini p, arisi m, pedretti a, ungari m, pinton pc. pseudolymphoma tattoo-induced. dermatol reports. 2011 nov 29;3(3):e47. doi: 10.4081/dr.2011.e47. pmid: 25386299; pmcid: pmc4211496.brady bg, gold h, et al. “self-reported adverse tattoo reactions: a new york city central park study.” contact dermatitis. 2015;73:91-9. 2. mitteldorf c, kempf w. cutaneous pseudolymphoma. surg pathol clin. 2017 jun;10(2):455-476. doi: 10.1016/j.path.2017.01.002. epub 2017 mar 22. pmid: 28477891.american academy of dermatology. “dermatologist warns consumers about complications linked to newer tattoo inks.” news release issued march 1, 2013. last accessed july 20, 2018 3. campolmi p, bassi a, bonan p, et al. cutaneous pseudolymphoma localized to black tattoo. j am acad dermatol. 2011;65(5):e155–7. 4. amann u, luger ta, metze d. lichenoid pseudolymphomatous tattooing reaction. hautarzt z für dermatol venerol verwandte geb. 1997;48(6):410–3. 5. kahofer p, el shabrawi-caelen l, horn m, kern t, smolle j. pseudolymphoma occurring in a tattoo. eur j dermatol. 2003 mar-apr;13(2):209-12. pmid: 12695144. 6. gutermuth j, hein r, fend f, ring j, jakob t. cutaneous pseudolymphoma arising after tattoo placement. j eur acad dermatol venereol. 2007 apr;21(4):566-7. doi: 10.1111/j.1468-3083.2006.01964.x. pmid: 17374006. 7. patrizi a, raone b, savoia f, bacci f, pileri a, gurioli c, neri i. tattoo-associated pseudolymphomatous reaction and its successful treatment with hydroxychloroquine. acta derm venereol. 2009;89(3):327-8. doi: 10.2340/000155550639. pmid: 19479145. 8. insect bite–like reaction in patients with hematologic malignant neoplasms aviv barzilai, md, msc; dorit shpiro, md; iris goldberg, phd; et alyasmin yacob-hirsch, msc; carlos diaz-cascajo, md; dina meytes, md; regina schiby, md; ninette amariglio, phd; henri trau, md. arch dermatol. 1999;135(12):1503-1507. doi:10.1001/archderm.135.12.1503; indian j dermatol venereol leprol. 2001 marapr;67(2):72-4. 9. abnormal insect bite reactions: a manifestation of immunosuppression of hiv infection? k ajithkumar 1, s george, p g babu.] covid-19 infection and vaccination may induce a brisk immune response that may be a hyperimmune response in some patients and has been associated with cutaneous inflammatory reactions [ front. immunol., 30 september 2021 sec. viral immunology. https://doi.org/10.3389/fimmu.2021.742941 10. hyperinflammatory immune response and covid-19: a double-edged sword li yin tan1,2, thamil vaani komarasamy1 and vinod rmt balasubramanian 11. munavalli gg, guthridge r, knutsen-larson s, brodsky a, matthew e, landau m. "covid-19/sars-cov-2 virus spike proteinrelated delayed inflammatory reaction to hyaluronic acid dermal fillers: a challenging clinical conundrum in diagnosis and treatment". arch dermatol res. 2022 jan;314(1):1-15. doi: 10.1007/s00403-02102190-6. epub 2021 feb 9. pmid: 33559733; pmcid: pmc7871141. 12. vojdani a, kharrazian d. potential antigenic cross-reactivity between sars-cov-2 and human tissue with a possible link to an increase in autoimmune diseases. clin immunol. 2020 aug;217:108480. doi: 10.1016/j.clim.2020.108480. epub 2020 may 24. pmid: 32461193; pmcid: pmc7246018. skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 307 editorial is absorption of sunscreen truly a problem? a careful review suggests it is not. graham h. litchman, do ms1, ryan m. svoboda, md ms2, darrell s. rigel, md ms3 1melanoma clinical research fellow, national society for cutaneous medicine, new york, ny 2fellow, department of dermatology, duke university school of medicine, durham, nc 3clinical professor of dermatology, new york university school of medicine, new york, ny skin cancer incidence continues to rise in the u.s. sunscreen usage is a critical component of any primary prevention (behavioral change to lower the risk of developing skin cancer) strategy to lower skin cancer rates. a recent paper by matta et al1 (and a related editorial by califf and shinkai[2]) has created controversy among clinicians and the media regarding several fda-approved sunscreen ingredients (avobenzone, oxybenzone, octocrylene) found to have measurable plasma levels after being applied to the skin of human volunteers. this is especially critical because multiple studies have shown that skin cancer risk is mitigated by avoiding and blocking ultraviolet (uv) radiation, the primary purpose of sunscreen usage. when critically reviewing the available data, it is clear that the findings of matta et al are not clinically material and may also have unintended risk. we are worried that the unfounded concerns raised by matta et al has the potential to lead to decreased usage of sunscreens, especially by those at greatest risk for developing skin cancer. the fact that sunscreen agents applied to the skin is found in plasma is not a new finding.3 merely having elevated plasma levels should not automatically be considered problematic as most topically applied medications have similar findings. fda-approved inorganic sunscreening agents such as micronized zinc oxide and titanium dioxide were declared as “generally recognized as safe and effective” (grase) this year by the fda.4 however, these ingredients have also been found in the subcutis after application5. this and the other negatives of these inorganic agents also need to be integrated into any further analyses of related issues. higher spf sunscreens have been demonstrated to be more protective in realworld settings.6 it is difficult to engineer higher spf sunscreens without using some of the fda-approved agents now suggested as non-grase. loss of these higher spf formulations has the potential to lead to sunscreens being less effective in skin cancer prevention. matta et al suggest performing larger-scale studies to further assess the implications of their findings. beyond the associated challenging logistics, it is important to recognize that this experiment has already skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 308 been indirectly performed. each summer weekend, millions of persons apply sunscreen with none of the hypothetical risks implied by matta et al being seen. in addition, their arbitrary selection of an upper limit of 0.5ng/ml1 is also problematic as there are no studies or data to support that concentration in the blood as a risk-specific level for sunscreens. perhaps of greatest concern is media coverage and secondary reporting of this paper has led many patients to conclude that sunscreens are dangerous – something u.s. dermatologists have been hearing from their patients every day. there simply is no evidence-based support for this claim. furthermore, the disclaimer in the last line of their paper was not adequate to avoid creating this now widespread public misconception which we believe has the real risk of leading to decreased sunscreen usage in the future. given that skin cancer incidence continues to increase and that sunscreens are a critical component of primary prevention, we hope that the concerns we raise are incorporated into evaluation strategies of sunscreen safety and efficacy moving forward. being diligent to ensure that conclusions are data-driven and that untoward negative effects on overall sunscreen usage are avoided is paramount. conflict of interest disclosures: dr. rigel is a consultant for neutrogena and johnson & johnson consumer funding: none corresponding author: darrell s. rigel, md ms clinical professor new york university medical center 35 east 35th street, suite 208 new york, ny 10016 212-684-4542 darrell.rigel@gmail.com references: 1. matta mk, zusterzeel r, pilli nr, patel v, volpe da, florian j, oh l, bashaw e, zineh i, sanabria c, kemp s, godfrey a, adah s, coelho s, wang j, furlong la, ganley c, michele t, strauss dg. effect of sunscreen application under maximal use conditions on plasma concentration of sunscreen active ingredients: a randomized clinical trial. jama. 2019 may 6. doi: 10.1001/jama.2019.5586. [epubahead of print] pubmed pmid: 31058986. 2. califf rm, shinkai k. filling in the evidence about sunscreen. jama. jun 4;321(21):20772079. pmid: 31058950 3. gustavsson gonzalez h, farbrot a, larkö o. percutaneous absorption of benzophenone-3, a common component of topical sunscreens. clin exp dermatol. 2002 nov;27(8):691-4. pubmed pmid: 12472548. 4. fda advances new proposed regulation to make sure that sunscreens are safe and effective. https://www.fda.gov/news-events/pressannouncements/fda-advances-new-proposedregulation-make-sure-sunscreens-are-safe-andeffective. accessed june 6, 2019 5. tan mh, commens ca, burnett l, snitch pj. a pilot study on the percutaneous absorption of microfine titanium dioxide from sunscreens. australas j dermatol. 1996 nov;37(4):185-7. pubmed pmid: 8961584. 6. williams jd, maitra p, atillasoy e, wu mm, farberg as, rigel ds. spf 100+ sunscreen is more protective against sunburn than spf 50+ in actual use: results of a randomized, doubleblind, split-face, natural sunlight exposure clinical trial. j am acad dermatol. 2018 may;78(5):902910.e2. doi: 10.1016/j.jaad.2017.12.062. pubmed pmid: 29291958. • efficacy analyses of scalp psoriasis, included patients with scalp involvement of at least 10% and a pga on the scalp of at least mild severity (grade 2) at baseline (cal/bdp cream n=112; vehicle n=38; table 1). • the pga treatment success on the scalp was significantly greater for cal/bdp cream (50.8%) than for vehicle (9.3%) at week 8 (p=0.0002) with comparable differentiation between the two arms also present at week 4 (p=0.0051) and week 6 (figure 1). • at week 1, 17 (15.2%) patients in the cal/bdp cream group and 0 (0.0%) patients in the vehicle group achieved pga treatment success on the scalp (figure 1). results andreas pinter1, morten præstegaard2, johan selmer2, adam reich3 1university hospital frankfurt am main, dept. of dermatology, frankfurt am main, germany; 2mc2 therapeutics, hørsholm, denmark; 3medical college of rzeszów university, dept. of dermatology, rzeszów, poland calcipotriene and betamethasone dipropionate cream demonstrates high treatment success in patients with scalp psoriasis table 1. number of patients and baseline disease • calcipotriene and betamethasone dipropionate (50 microgram/g cal and 0.5 mg/g bdp) cream (cal/bdp cream) is based on padtm technology enabling development of an easy to apply, aqueous cream of cal and bdp, despite their known ph-related instability when combined in the presence of water. • the objective of this subgroup analysis is to present data from a phase 3 trial conducted in europe on the efficacy of cal/bdp cream in scalp psoriasis. introduction • w riting support was provided by anja snel-prentø. • the study was funded by mc2 therapeutics. acknowledgements conclusions • the scalp is a common location of involvement of plaque psoriasis and successful management of scalp psoriasis includes topical therapies that are effective and acceptable to the patient. • cal/bdp cream is a novel topical treatment for plaque psoriasis based on pad™ technology. • cal/bdp cream demonstrated high pga treatment success and satisfaction, fast onset of action and a favourable safety profile in patients with scalp psoriasis. methods • efficacy and safety of cal/bdp cream was evaluated in a phase 3, randomized, multicenter, investigator-blind, parallel-group trial. patients were instructed to apply the trial medication topically once daily to affected areas for up to 8 weeks. • efficacy analyses of scalp psoriasis, included patients with scalp involvement of at least 10% and a physician’s global assessment (pga) on the scalp of at least mild severity (grade 2). • the percentage of patients with pga success on the scalp was defined as a minimum two-grade decrease from baseline to week 8 in pga score of psoriasis severity on the scalp to clear (grade 0) or almost clear (grade 1). • statistical analyses of pga treatment success were based on multiple imputations and a treatment policy strategy on the full analysis set, scalp psoriasis subgroup using a logistic regression model including randomized treatment and analysis site as independent variables. • pga treatment satisfaction defined as clear (grade 0) or almost clear (grade 1) disease was analyzed using descriptive statistics based on observed cases. figure 3. improvement of scalp psoriasis after treatment with cal/bdp cream pictures from mc2-01-c7 phase 3 trial; informed consent to publish pictures has been obtained from the patient. figure 1. pga treatment success on the scalp by weeks of treatment pga, physician’s global assessment. bdp, betamethasone dipropionate; cal, calcipotriene. • 29.5% of patients in the cal/bdp cream group achieved pga treatment satisfaction (clear or almost clear) on the scalp already at week 1, increasing to 68.2% at week 8 compared to 25.0% in the vehicle group (figure 2). • figure 3 shows representative examples of patients achieving pga treatment success on the scalp at week 1 and clearance at week 4 after treatment with cal/bdp cream. • overall, safety assessments during the trial demonstrated that cal/bdp cream was well-tolerated. figure 2. pga treatment satisfaction on the scalp by weeks of treatment cal/bdp cream vehicle number of patients in the full analysis set 213 68 number of patients in the scalp analyses 112 38 pga on the scalp at baseline: mild (pga grade 2) 55 17 moderate (pga grade 3) 53 21 severe (pga grade 4) 4 0 full analysis set, scalp psoriasis subgroup, treatment policy strategy, multiple imputations. p-values represent comparison between cal/bdp cream and vehicle * 15.2 29.2 44.3 50.8 0.0 3.1 7.0 9.3 0 10 20 30 40 50 60 0 2 4 6 8 % p g a t re a tm e n t s u c c e s s weeks cal/bdp cream vehicle 29.5 51.8 63.3 68.2 0.0 12.1 15.6 25.0 0 20 40 60 80 0 2 4 6 8 % p g a t re a tm e n t s a ti s fa c ti o n weeks cal/bdp cream vehicle baseline week 1 week 4 week 8 p=0.0002 p=0.0051 full analysis set, scalp psoriasis subgroup, observed cases. skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 743 compelling comments at-home microneedling of acral skin to increase percutaneous absorption of imiquimod kate e. beekman, bs¹, danielle k. depalo, md2, james m. grichnik, md, phd2,3, lilia m. correa, md2,3, jonathan s. zager, md1,2 1usf health, morsani college of medicine, tampa, fl 2moffitt cancer center, department of cutaneous oncology, tampa, fl 3usf health, department of dermatology and cutaneous surgery, tampa, fl increased thickness of acral skin can reduce percutaneous absorption of topical imiquimod and hinder development of desired inflammatory response,1 presenting a challenge to its efficacy in treating acral skin malignancies. an 85-year-old female patient with a history of 1.3mm breslow depth, non-ulcerated, acral lentiginous melanoma of the left plantar foot declined standard-of-care surgical reexcision of persistent malignant melanoma in situ (mmis) at the margins after three prior excisions (figure 1a). as an alternative, she underwent a 3-month course of off-label topical imiquimod 5% applied 5x weekly per pandit et al.’s protocol.2 the patient previously received a course of imiquimod with tretinoin for residual mmis prior to the most recent surgical excision; however, desired inflammatory and disease response was not achieved. this time, multiple steps were taken to increase absorption of imiquimod. first, curettage of the positive margin was performed in office to remove hyperkeratotic stratum corneum. additionally, the patient was instructed to purchase an at-home microneedling kit and use the device in 3 directions along the positive margin for 1 minute prior to each imiquimod application. she was also directed to occlude the area with plastic wrap following application. after the 3-month treatment course, no residual pigmentation was present. at 12-month follow-up, the patient remained without evidence of disease (figure 1b). figure 1. (a) left plantar foot site of previous invasive melanoma status post 3 surgical excisions with persistent residual mmis at the 69-12 o’clock (medial) margin before imiquimod treatment with microneedling. (b) left plantar foot with sustained absence of residual pigmentation at 12-month follow-up from completion of imiquimod therapy with microneedling. clinical problem practice pearl skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 744 while microneedling has been demonstrated to improve intradermal penetration of imiquimod in vitro,3 it is not always feasible for patients to undergo microneedling in clinic before each topical therapy application. although at-home microneedling devices are unregulated and pose a risk of infection when not properly sanitized, risks can be minimized with healthcare provider oversight. we have found that at-home microneedling can be safely performed under physician direction and may improve efficacy of imiquimod in treating malignancies of acral skin. conflict of interest disclosures: j.s.z. has advisory board relationships and has received fees from with merck, novartis, philogen, castle biosciences, pfizer and sun pharma. he also received research funding from amgen, delcath systems, philogen, provectus and novartis. he serves on the medical advisory board for delcath systems. l.m.c. is a consultant for accutec and a consultant and researcher for novartis pharmaceutical. she also serves on the advisory board for the jacinto convit world organization and the dermatology advisory council for melanoma research foundation. j.m.g is a consultant for galileo group and canfield scientific and serves on skin advisory board for regeneron and dermatology advisory council for melanoma research foundation. he has received clinical trial support from novartis, eli lilly, dermira, elorac, boehringer and amgen. funding: none corresponding author: jonathan s. zager, md, facs, fsso 10920 n. mckinley drive, room 4123 tampa, fl 33612 phone: (813) 745-1085 email: jonathan.zager@moffitt.org references: 1. nakamura y, fujisawa y. diagnosis and management of acral lentiginous melanoma. curr treat options oncol. 2018;19(8):42. published 2018 jun 27. doi:10.1007/s11864-018-0560-y 2. pandit as, geiger ej, ariyan s, narayan d, choi jn. using topical imiquimod for the management of positive in situ margins after melanoma resection. cancer med. 2015;4(4):507-12. epub 20150126. doi: 10.1002/cam4.402. pubmed pmid: 25620351; pubmed central pmcid: pmc4402064. 3. al-mayahy mh, sabri ah, rutland cs, et al. insight into imiquimod skin permeation and increased delivery using microneedle pretreatment. eur j pharm biopharm. 2019;139:3343. doi: 10.1016/j.ejpb.2019.02.006 conclusion skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 309 original research skinspecs: a mobile solution that addresses an unmet need for tracking chronic skin diseases in the office and at home olga k. afanasiev, md, phd1, mika tabata, bs2, akhila narla, ba2, gregory scott, md, phd3, justin m. ko, md, mba1 1stanford health care, department of dermatology 2stanford school of medicine 3stanford health care, department of pathology chronic skin diseases are challenging and frustrating to manage for both patients and physicians. patients often experience difficult-to-capture flares in between visits and see multiple providers for their skin condition. dermatologists currently use subjective measures to document chronic skin conditions; this is problematic at follow up visits when dermatologists lack abstract introduction/objectives: currently there are no portable solutions to robustly document and longitudinally monitor dynamically changing chronic skin conditions. this study set out to engineer and test a mobile-based 3d imaging solution for chronic skin diseases to enhance clinical workflow and patient care. methods: skinspecs uses smartphone-captured videos of patients’ skin disease and renders 3d true-to-life models that were evaluated by stanford health care dermatologists. results: we utilized video input to accurately reconstruct interactive 3d models of 16 different skin conditions from 31 patients. assessment of skinspecs 3d reconstruction is faster (p<0.05) compared to descriptive exam, standard photographs or original videos. dermatologists maintained highest accuracy, confidence and satisfaction with 3d reconstruction. dermatologist preferred skinspecs for documentation over other capture modalities. skinspecs was favorably used by dermatologists, with high satisfaction with resolution, breadth of visual information, time and ability to pick up incidental findings. impact: we identified a proof-of-concept solution to objectively and robustly capture skin disease, with an office and home workflow that is acceptable to providers and patients. this fast, scalable method is deployable on smartphones and could be utilized to augment clinical decision making in the clinic and to empower patients at home. introduction 2019 resident research competition – 1st place skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 310 confidence in assessing disease change in patients seen by another provider.1 while there are many emerging tools and mobile applications for monitoring individual neoplasms,2 dermatologists and patients lack an objective and efficient tool to robustly document and longitudinally monitor changes in chronic and inflammatory skin conditions. existing smartphone applications either track pre-existing and patient-defined lesions on specific anatomic body parts or have only a rough full body overlay of disease. additionally, office photography is inconsistent, overly cumbersome and laborintensive for clinical workflows. lastly, 3d full body multi-camera imaging systems are expensive and with limited access. this study engineers and tests a proof-of-concept smartphone-based imaging solution “skinspecs” that has the potential to improve current workflows in the office and skin disease monitoring strategies at home to positivity impact patient care. institutional review board approval was received for this study and patients provided written consent. video capture: high resolution videos (1080p-4k at 30-60 fps) using iphone 7 and x were obtained from 31 patients seen at stanford health care dermatology clinic from july 2018 to january 2019. 180°-360° video of the full distribution of skin disease or subject of interest was obtained. ambient clinic lights were used during video capture. no special setup or training for video capture was required. mannequins were used in this study and simulated markings or stickers were applied to minimize ambiguity and to ensure the participants surveyed did not have to rely on clinical knowledge. 3d model rendering and analytics: captured videos were rendered using photoscan (agisoft, llc) photogrammetry software to create a 3d model that was exported to a ~5-50 megabyte pdf that can be viewed on any device. this 3d reconstruction software automatically generates textured polygonal 3d models using the digital photographs extracted from videos. we automatically extract frames from videos using the scripting language for vlc player, an open source video editing software, and generate individual compressed images of frames using the lossy “jpeg” format. frames are batch processed into 3d models using photoscan .xml commands which stepwise 1) align frames in three dimensional space using a proprietary linear coregistration algorithm, 2) generate sparse then dense point clouds based on the transformation matrix which represents the perspective shift/parallax effect, 3) generate a tessellated 3d model using the dense point cloud as vertices, and finally 4) overlay a high in-plane resolution colored texture onto the model surfaces. we utilized 3d pdf reader (tech soft 3d version 3.8) to view the 3d output on the ipad. for analytics and surface area calculations, we use meshlab (2016) to manually select the lesion area using a multipoint polygon region‐selection tool for precise planimetry applications. survey data: stanford health care dermatologists were randomly assigned and anonymously surveyed regarding various “capture” modalities that were presented on an ipad pro. captures included: 1) 3d reconstruction obtained as described above, 2) descriptive exam (which was obtained either from consensus exam from dermatologist asked to describe a mannequin or directly gathered from a clinic note), 3) photographs, or 4) video. complete survey questionnaires are available from the methods skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 311 corresponding author. a total of 14 dermatologists were randomized to closely examine 1 specific capture modality and answer specific questions. 34 dermatologists compared all 4 captures side by side and were asked about their preferred capture of choice. data analyses were performed in excel 16.0. we captured 31 short videos (mean time=31.8 seconds; range 8-75 seconds) for 3d reconstruction from patients with 16 dermatologic conditions that were rendered into life-like interactive 3d reconstructions as described in methods above (figure 1-2). assessment of skinspecs 3d reconstruction is fast and accurate with high confidence and satisfaction (figure 3). dermatologists were presented with one of four mannequin captures: 3d reconstruction, descriptive exam (text), standard photographs or video (figure 3a). they were then asked to identify color and shapes of specific lesions as well as percent of face that was erythematous. physicians who used the 3d reconstruction answered these questions significantly faster (mean=27.8 seconds) than those with descriptive exam (64.7 seconds), photo (51.3 seconds) or video (50.5 seconds) captures, (p<0.05, figure 3b). importantly they maintained as high or higher rate of accuracy, confidence in answers and satisfaction with capture compared to those with descriptive exam, photo or video captures (figure 3c-3d). survey regarding satisfaction included satisfaction with the overall capture for the purposes of documentation and monitoring for change, and, as applicable, satisfaction with resolution, breadth, ability to pick up incidental findings. skinspecs 3d reconstructions has analytic capabilities to accurately and objectively extract data from the life-like subject. the 360 view of 3d model allows for segmentation of face and extraction of lesions (figure 4a) and 3-dimentional surface areas (figure 4b). we show that while the dermatologists evaluating the 3d capture come closest to the true estimate of erythematous surface area (15.7% of face), dermatologists overestimate the surface area using all modalities: 3d capture (23.8%), photographs (28.3%), descriptive exam (30%, most were not able to answer from provided description), or video (31.9%) (figure 4c). dermatologist preferred skinspecs 3d reconstruction over written description, standard photographs or video capture for documentation, but photographs were the capture of choice for longitudinal monitoring of chronic skin disease and for educational purposes (figure 5). dermatologists were presented with 1 of 4 patient captures: 3d reconstruction, descriptive exam, standard photographs or video (figure 5a). for documentation, dermatologists preferred to use 3d capture (29.4%) over descriptive exam (17.6%), photographs (23.5%) or video (17.6%) (figure 5b). some preferred a combination of several captures (11.8%). for tracking changes between visits, dermatologist preferred to use photographs (41.2%) over 3d captures (29.4%), descriptive exam (5.9%), video (17.6%) or combination (5.9%). lastly, for education purposes, physicians had a preference for photographs (48.3%) compared to 3d captures (24.1%), descriptive exam (3.4%) or video (24.1%). in summary, we propose an easy workflow that is able to objectively capture skin disease and its emotional and functional impact on the patient and then digest it to a results skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 312 capsule summary that can be interpreted by both the patient and provider (figure 6). figure 1. skinspecs workflow from video to skinspecs 3d reconstruction. a) capture of video using ambient conditions without any prior training or setup required using any mobile device. b) extraction of relevant frames from video with virtual and generation of a dense cloud. c-d) 3d reconstruction model of a subject, which can be viewed and manipulated using adobe acrobat reader or other freely available applications that can be downloaded on a mobile device. skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 313 figure 2. diversity of captured and reconstructed skin diseases. a) table listing all captured skin disease. b-g) sample 3d reconstructions (presented here as still images, however 3d pdfs are fully interactable and can be provided upon request): b) psoriasis, c) lipodermatosclerosis, d) dyshidrotic eczema on hand, e) melanoma on right cheek, f) atypical mole syndrome, g) nevi and xerosis. skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 314 figure 3. assessment of skinspecs 3d reconstruction, descriptive exam, photographs and video captures in terms of time, accuracy, confidence and satisfaction among dermatologists. assessment of skinspecs 3d reconstruction is fast and accurate with high confidence and satisfaction. a) representative captures that dermatologists were provided with during survey. b) length of time spent evaluating and answering 3 specific questions (color of simulated lesion, shape of lesion and body surface area) regarding the model. c) confidence of assessing lesional color and shape as well as body surface area (bsa) among 4 capture on a likert 5-point scale. d) summary of time, accuracy, confidence (agree to strongly agree on likert scale) and satisfaction (agree to strongly agree on likert scale) among 4 captures. *p<0.05, **p<0.01. skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 315 figure 4. analytic capabilities of skinspecs 3d capture. a) 360 view of 3d model allows for segmentation of face and extraction of relevant findings. b) analysis of surface area of full face (left with red-orange mask overlay) and erythematous component only (right with red-orange mask overlay). c) comparison of physician estimates regarding percentage of face that is erythematous from 3d reconstruction, descriptive exam, photographs, or video capture compared to the calculated true surface area involvement (dashed red line at 15.7%). skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 316 figure 5. dermatologists’ preference among 4 different capture modalities for documentation, monitoring and education purposes. a) representative captures provided to dermatologists for assessment. b) preferred capture modalities for in-office documentation, disease monitoring between visits and educational purposes among dermatologists. skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 317 figure 6. proposed schematic of a skinspecs workflow. a short video of relevant body part with skin findings is obtained (no prior training or setup required). the video is then rendered into a 3d model which can be interactively viewed on any device. patients have the option of additional inputs (such as symptoms, emotional or functional burden, current treatments, etc.). a summary dashboard integrates relevant data captured over time for monitoring by patients and or evaluation by physicians. skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 318 dermatologists and patients currently lack an objective, universal, cheap, easy way to document and track changes in chronic skin diseases. this is a problem because physicians cannot accurately assess dynamic change in disease severity or response to treatment between office visits, and patients cannot accurately capture and relay their functional and emotional burden of disease while at home. this leads to frustration among physicians and patients due to delay in diagnosis, inadequate control of disease and inconsistency in care. this study engineers and tests skinspecs, a smartphone-based, fast, accurate, scalable, low-cost, proof-of-concept solution that is immediately deployable to patients and physicians and could be utilized as a clinical decision support tool to provide better care to our patients with chronic skin diseases. to the authors’ knowledge, this is the first clinically tested mobile 3d imaging solution that robustly captures a large diversity of chronic skin conditions. we show that skinspecs enables a fast and accurate assessment of chronic skin diseases with high confidence and satisfaction among dermatologists. currently, most physicians use subjective measures (such as gestalt, descriptive exam, body surface area (bsa)) to document chronic skin conditions as validated scoring systems and photographs are cumbersome and time consuming.1 notably, prior literature showed that seemingly objective numeric bsa assessment is poorly estimated by physicians and 2d capture underestimates surface area by 20%.3–5 furthermore, poor descriptive terms and lack of photographs from referring physicians has led to delayed follow up.6 in our study, descriptive exam, which is currently the gold standard documentation, underperformed in speed, accuracy, confidence and satisfaction compared to 3d reconstruction, photographs or videos. we report that dermatologists came closest to the true bsa when evaluating skinspecs 3d reconstruction compared to all other modalities. furthermore, the 3d capture has the potential to automatically measure skin surface changes and to dynamically and precisely track these changes over time. this ability to accurately capture disease severity, pattern, location and response to treatment is critical to dermatologists’ ability to move along their therapeutic ladders. interestingly, although providers preferred skinspecs 3d reconstructions for documentation, they preferred standard photographs for monitoring disease between visits and for educational purposes. this could be because they are most familiar with standard photography, which is the capture of choice for atypical/dysplastic nevi and occasionally for rashes during an office visit. similarly, most dermatology curriculums rely on photographs from textbooks and image atlases. unfortunately, these resources are unable to accurately capture or convey lesional topography (scale, induration, thickness, etc.) or distribution of disease. however, medical education curriculums are now integrating 3d digital virtual simulations to supplement standard curriculums.7,8 novel repository of 3d reconstructions will better simulate in-person visits to increase medical providers' exposure to rare skin diseases (such as those presented at grand rounds) and many varied presentations of common skin conditions, preserving the ability to revisit them for clinical and didactic purposes. skinspecs addresses patients’ need to document their skin disease. currently, in office professional whole-body photography is too time consuming and infrequent to be discussion skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 319 useful, and multi-camera imaging systems are expensive and scarcely available.5 a recent study showed that while 90% of patients report it is moderately to extremely important to track their disease, only 16% of patients consistently do, citing lack of optimized tools for documentation. indeed, patients are willing to spend 10-15 minutes weekly to monthly for documentation, with a preference of using a smartphone.1 given that skinspecs capture takes 1 minute at most, this is well within the realm of time patients are willing to spend to document their disease, making the skinspecs workflow conducive to frequent and robust disease capture at home. integrating the objective disease summary simultaneously with patient-reported outcomes (symptoms, emotional and functional impact)9,10 can further fully capture the impact of the disease on the patient. dermatologists only recently, but successfully, integrated photography of concerning lesions and biopsy sites into their clinical workflow, which sets precedence for a similar workflow adaptation for chronic skin diseases. one could argue that thorough and robust photo documentation is even more critical for dynamically changing skin rashes that are often elusive during sporadic office visits. an integrated dashboard summary that includes relevant compiled analytics of disease trajectory and response to treatments between office visits and at home could save the physician time in history gathering that currently relies on imperfect memories. future applications of similar workflows could include inpatient consult services, teledermatology platforms, surgical follow ups, cosmetic services and clinical trials. furthermore, as we gather larger data sets of full body images as well as other complex associated features (quality of life, associated symptoms, responses to treatments), these could all be used to train deep neural networks and artificial intelligence algorithms for augmented clinical decision making. as hospital systems and payers are moving towards value-driven and precision medicine, individualized disease tracking tools could lead to improved outcomes at a decreased cost to the healthcare system. skinspecs could be easily deployed for primary care or the teledermatology workflows. importantly the centers for medicare & medicaid services have finalized plans to reimburse healthcare providers for certain remote patient monitoring and telehealth services.11 limitations of this study include a single academic center recruitment of patients and physicians. the study design included a second person who captured patient videos, which can make it impractical for patients that lack assistance for video capture. future steps include validation of this tool for specific diseases and determination of resolution limitations. in summary, skinspecs is a scalable and mobile-device deployable solution that enables practical, fast, cheap, and accurate capture of high-quality data with great potential to improve care, patient empowerment, educational tools and dermatology access. conflict of interest disclosures: none funding: stanford society of physician scholars irb/consent: an appropriate institutional review board approved the project, and informed consent was appropriately obtained. corresponding author: olga afanasiev, md, phd olga54@gmail.com skin september 2019 volume 3 issue 5 copyright 2019 the national society for cutaneous medicine 320 references: 1. afanasiev ok, tabata m, ko jm. the need for objective and remote tracking of chronic skin diseases. submitted manuscript. 2019. 2. guido n, hagstrom el, ibler e, et al. a novel total body digital photography smartphone application designed to detect and monitor skin lesions: a pilot study. j surg dermatol. 2018;3(2). doi:10.18282/jsd.v3.i2.177 3. ramsay b, lawrence cm. measurement of involved surface area in patients with psoriasis. br j dermatol. 1991;124(6):565-570. doi:10.1111/j.1365-2133.1991.tb04952.x 4. nichter ls, williams j, bryant ca, edlich rf. improving the accuracy of burn-surface estimation. plast reconstr surg. 1985;76(3):428433. 5. kohli i, isedeh p, al‐jamal m, et al. threedimensional imaging of vitiligo. exp dermatol. 2015;24(11):879-880. doi:10.1111/exd.12791 6. börve a, dahlén gyllencreutz j, terstappen k, et al. smartphone teledermoscopy referrals: a novel process for improved triage of skin cancer patients. acta derm venereol. 2015;95(2):186190. doi:10.2340/00015555-1906 7. deng x, zhou g, xiao b, zhao z, he y, chen c. effectiveness evaluation of digital virtual simulation application in teaching of gross anatomy. ann anat anat anz off organ anat ges. 2018;218:276-282. doi:10.1016/j.aanat.2018.02.014 8. zilverschoon m, kotte emg, van esch b, ten cate o, custers ej, bleys rlaw. comparing the critical features of e-applications for threedimensional anatomy education. ann anat anat anz off organ anat ges. 2019;222:28-39. doi:10.1016/j.aanat.2018.11.001 9. swerlick ra, zhang c, patel a, chren mm, chen s. the skindex-mini: a streamlined qol measurement tool suitable for routine use in clinic. j am acad dermatol. december 2018. doi:10.1016/j.jaad.2018.12.035 10. armstrong a, puig l, langley r, et al. validation of psychometric properties and development of response criteria for the psoriasis symptoms and signs diary (pssd): results from a phase 3 clinical trial. j dermatol treat. 2019;30(1):27-34. doi:10.1080/09546634.2017.1364694 11. final policy, payment, and quality provisions changes to the medicare physician fee schedule for calendar year 2019 | cms. https://www.cms.gov/newsroom/fact-sheets/finalpolicy-payment-and-quality-provisions-changesmedicare-physician-fee-schedule-calendar-year. accessed april 16, 2019. skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 551 skinmages anal monkeypox lesions david crasto, do1, moises lutwak, md2, eduardo krajewski, md, facs, fascrs3, eduardo weiss, md, faad4 1larkin community hospital south, south miami, fl 2broward health systems, ft. lauderdale, fl 3gastrohealth, miami, fl 4university of miami miller school of medicine, miami fl a middle-aged adult male with a history of well-controlled human immunodeficiency virus (hiv) infection presented to the emergency department (ed) for new-onset perianal lesions. according to the patient, his symptoms began one week prior as an initial febrile illness with mild headaches followed by the development of small, painless bumps approximately 24 hours later. he denied any foreign travel or sick contacts but did however admit to recent sexual encounters with multiple new male partners. on exam, multiple flesh-colored umbilicated papules with necrosis were observed on bilateral perianal skin (figure 1). remainder of the physical exam was unremarkable, including inguinal lymph node palpation, as well as initial diagnostic and laboratory studies in the ed. the patient was subsequently admitted for further investigation of suspected infectious etiology, including a perianal biopsy along with viral and bacterial cultures. histopathology illustrated epidermal necrosis with an abundance of neutrophils and viral cytopathologic changes featuring skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 552 multinucleated, syncytial keratinocytes (figure 2). cultures resulted negative for bacterial growth, as well as adenovirus, herpes simplex virus (hsv)-1, hsv-2, cytomegalovirus (cmv), and varicella zoster virus (vzv). given the high index of suspicion for monkeypox infection, a lesional swab was sent for polymerase chain reaction (pcr) and found positive for orthopoxvirus dna. based on the history, clinical, and pathologic findings, coupled with the pcr results, a diagnosis of monkeypox infection was made. subsequent testing for sexually transmitted infections (stis) was negative. one week later at follow-up, he reported complete resolution of the lesions. monkeypox is a zoonotic orthopoxvirus endemic to central and western africa first reported as an infection in humans in 1970. the clinical course of “classic” monkeypox infection bears a striking resemblance to smallpox, causing much concern in its initial emergence as a human infection.1 typically, a prodromal illness characterized by fever, headache and myalgias precedes the onset of the monkeypox rash which, in most cases, begins on the head with subsequent cephalocaudal spread and spontaneous resolution in 2-3 weeks.2,3 one study involving 282 patients reported the presence of lymphadenopathy as the most important distinguishing feature from smallpox and vzv.2 the 2022 global outbreak of monkeypox is unique regarding several key features. previously, affected individuals had a history of travel to a known endemic region. furthermore, the prodrome is often times absent, or much milder, as compared to classic monkeypox.1,3 moreover, human to human contact appears to predominate disease transmission during this outbreak in contrast from animal to human.3 men who have sex with men (msm) are at a particularly heightened risk, and anogenital lesions are frequently being reported.3,4 a recent study by thornhill et al. described 528 infections across 16 countries; among these, 98% occurred in msm and 73% presented with anogenital lesions. preceding symptoms of fever and lymphadenopathy were most common (62% and 56%, respectively). spontaneous resolution occurs within 2-3 weeks with scarring and atrophy typically seen at the sites of infection.3 conflict of interest disclosures: none funding: none corresponding author: david crasto, do larkin community hospital south miami phone: 954-807-9433 email: davecrastodo@gmail.com references: 1. harris e. what to know about monkeypox. jama 2022 jun;327(23):2278-9. 2. jezek z, szczeniowski m, paluku km, mutombo m. human monkeypox: clinical features of 282 patients. j infect dis. 1987;156(2):293-8. 3. thornhill jp, barkati s, walmsley s, j. rockstroh, a. antinori, l.b. harrison, r. palich, a. nori, i. reeves, m.s. habibi, v. apea, c. boesecke, l. vandekerckhove, m. yakubovsky, e. sendagorta, j.l. blanco, e. florence, d. moschese, f.m. maltez, a. goorhuis, v. pourcher, p. migaud, s. noe, c. pintado, f. maggi, a.-b.e. hansen, c. hoffmann, j.i. lezama, c. mussini, a.m. cattelan, k. makofane, d. tan, s. nozza, j. nemeth, m.b. klein, and c.m. orkin, for the share-net clinical group. monkeypox virus infection across 16 countries – april-june 2022. n engl j med 2022; doi: 10.1056/nejmoa2207323. 4. sherman s. monkeypox genital lesions. n engl j med 2022;387(1):66. abametapir lotion, 0.74% demonstrates high elimination rates of head lice with a single application in phase 3 trials lydie hazan, md1; robert s haber, md2; michael husseman, md3; katie shepherd4; sharon hanegraaf5; tiina ahveninen5; lisa jenkins6; hugh alsop5; vernon m bowles, phd7 1axis clinical trials, los angeles, ca; 2case western university school of medicine, cleveland, oh; 3wee care pediatrics, university of utah school of medicine, salt lake city, ut; 4the shepherd institute for lice solutions, west palm beach, fl; 5hatchtech pty ltd, melbourne, australia; 6virtual regulatory solutions, audubon, pa; 7university of melbourne, melbourne, australia results introduction objective methods financial support: this study was funded and supported by hatchtech pty ltd, melbourne, australia. drl publication #783 ¾ successful treatment of head lice infestations may be hampered by limited ovicidal efficacy of current treatments1, increasing resistance to commonly used treatments2, and poor adherence to 2-application treatment regimens. ¾ abametapir lotion, 0.74%, contains the active ingredient abametapir, a compound with a new mode of action3 being developed for the single-application treatment of head lice infestation. the objective of the current studies was to evaluate the efficacy of a single 10 minute application of abametapir lotion, 0.74% for the treatment of head lice infestation in subjects 6 months of age and older. ¾ two randomized, double-blind, vehicle-controlled, parallel-group, multi-center studies were conducted in subjects aged ≥ 6 months with active head lice infestations along with household members with ≥ 1 live louse. ¾ households were equally randomized to receive abametapir lotion, 0.74% or vehicle. ¾ product was applied to dry hair for 10 minutes and rinsed with water. no nit combing was performed. following treatment, subjects were inspected for live lice on days 1, 7, and 14. ¾ treatment success was defined as being louse-free at all post-baseline visits through day 14. ¾ enrollment included a total of 704 subjects with comparable demographics in each study. ¾ for all subjects treatment success was 88.2% (165/187) and 81.0% (132/163) with abametapir lotion, 0.74% for the two studies, respectively, compared with 62.0% (119/192) and 60.5% (98/162) for the vehicle groups (both p<.001) (table1). ¾ the most common treatment emergent adverse events were erythema, rash, and skin burning sensation (table 2). ¾ a single, 10-minute application of abametapir lotion, 0.74% was effective in treating active head lice infestation within 14 days in subjects 6 months or older. ¾ in this study, the most common adverse events were erythema, rash, and skin burning (range 2.6% to 4.0%) and there were no serious adverse events. references 1. mumcuoglu ky, effective treatment of head louse with pediculicides. j drugs dermatol. 2006;5:451-452. 2. durand rs, bouvresse s, berdjane z, et al. insecticide resistance in head lice: clinical parasitological and genetic aspects. clin microbiol infect. 2012;18:338-344. 3. van hiel mb, breugelmans b, pagel cm, et al. the ovicidal, larvacidal and adulticidal properties of 5,5’-dimethyl-2,2’-bipyridyl against drosophila melanogaster. plos one. 2012;7:e49961. table 2. adverse events occurring in ≥ 1% of the abametapir lotion, 0.74% group and at a greater frequency than in the vehicle group (studies 1 & 2) adverse reactions abametapir lotion, 0.74% n=349 vehicle lotion n=350 erythema 14 (4.0%) 6 (1.7%) rash 11 (3.2%) 8 (2.3%) skin burning sensation 9 (2.6%) 0 (0.0%) contact dermatitis 6 (1.7%) 4 (1.1%) vomiting 6 (1.7%) 2 (0.6%) eye irritation 4 (1.2%) 2 (0.6%) hair color changes 3 (1.0%) 0 (0.0%)*overall treatment success defined as being louse-free at all post-baseline visits through day 14 table 1. overall treatment outcome by study & treatment group study 1 % (n) abametapir lotion, 0.74% (n=187) vehicle lotion (n=192) treatment success 88.2% (165)* 62.0% (119) treatment failure 11.8% (22) 38.0% (73) study 2 % (n) abametapir lotion, 0.74% (n=163) vehicle lotion (n=162) treatment success 81.0% (132)* 60.5% (98) treatment failure 19.0% (31) 39.5% (64) conclusions fc17posterpromiushazanabametapirlotion.74.pdf skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 161 brief articles granulomatous chelitis: a case report jordan genece1, justin chu1, stephanie liu do mba2, nahla shihab md3, jonathan ungar md4 1research fellow, department of dermatology, icahn school of medicine at mount sinai, new york, ny 2dermatopathology fellow, icahn school of medicine at mount sinai, new york, ny 3clinical dermatology fellow, department of dermatology, icahn school of medicine at mount sinai, new york, ny 4assistant professor of dermatology, department of dermatology, icahn school of medicine at mount sinai, new york, ny granulomatous cheilitis is an inflammatory disorder characterized by swelling of the lips.1-4 the etiology of granulomatous cheilitis is unclear.1-2 the inflammation is generally painless and may be intermittent initially, but tends to persist over time.1 due to the inconsistency of the presentation of symptoms over time and the difficulty in isolating an underlying mechanism a final diagnosis of granulomatous cheilitis may only be rendered after a few years.4 granulomatous cheilitis is considered a rare entity, with only a few cases reported in the literature.2 we report a case of biopsy proven granulomatous cheilitis in a young caucasian man introduction introduction: granulomatous cheilitis is a rare condition, with an unknown etiological pathway, resulting in inflammation of the lips. this case report demonstrates the efficacy of intralesional triamcinolone with this persistent disorder. case report: a 19-year old man presented with orofacial swelling on the right side for approximately 18 months. previous treatments of minocycline and metronidazole were unsuccessful. the patient has no other symptoms and an unremarkable family history. a regiment of topical anesthetic benzocaine gel and intralesional triamcinolone showed significant improvement. discussion: this rare condition has many possible contributory factors with very few established treatments. our patient appeared to present either granulomatous cheilitis or monosymptomatic melkersson-rosenthal syndrome. our primary goal was to abate the patient’s symptoms for their comfort, hence the implication of the benzocaine gel. conclusion: there are various therapeutic methods described, however we believe intralesional triamcinolone injections with prior application of topical anesthetic to ease discomfort, could be an alternative treatment. abstract skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 162 successfully treated with triamcinolone intralesional injection. a 19-year-old caucasian man presented with swelling of the upper lip, primarily on the right side. the swelling had been persistent for roughly 18 months. there was no facial and other oral swelling. he had no other systemic symptoms, including respiratory and gastrointestinal. he had no personal or family history of crohn’s disease. he also had no history of atopy and no therapy with an ace inhibitor or calcium channel blocker. upon physical examination there was asymmetrical edema of the right side of upper mucosal lip (figure 1). a skin biopsy from his right side of upper mucosa lip revealed collections of histiocytes in the dermis and slight spongiosis that are consistent with granulomatous cheilitis (figure 3). pas and fite stains failed to reveal microorganisms. he underwent pinprick testing and north-american panel patch testing which were all negative. chest x-ray was negative for sarcoid. during his visits, he repeatedly mentioned how distressed he was with his condition. he was treated with minocycline 100 mg bid and metronidazole 500mg bid for one month with no improvement. he had minimal improvement with intralesional injection of 10mg/cc triamcinolone but complained about the pain. we then decided to apply 10% benzocaine gel before injecting him with 20mg/cc triamcinolone. after 5 injections every two weeks, he had significant improvement (figure 2). figure 1. patient at his initial presentation to our clinic. figure 2. patient after five sessions of treatment. figure 3. nodular aggregates of epithelioid histiocytes with admixed lymphocytes. case report skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 163 granulomatous cheilitis is a recurrent and persistent asymptomatic swelling of the lips.5 it is considered as part of orofacial granulomatosis (ofg), which is an entity describing orofacial swelling caused by noncaseating granulomatous inflammation in the absence of systemic disease.2,6 the incidence of granulomatous cheilitis is estimated to be 0.08%.5-7 it has no predilection to sex, age, or race.6,7 a cellmediated hypersensitivity reaction, chronic antigenic stimulation, and cytokine production, all leading to granuloma formation, have been suggested as the etiology of granulomatous cheilitis.8 the typical manifestation of granulomatous cheilitis is relapsing and non-tender swelling of the lips that slowly becomes permanent.9 it may lead to possible facial distortion that cause significant psychological impact on a young patient.6,9 granulomatous cheilitis may occasionally present as melkersson-rosenthal syndrome (mrs), which is a triad of lip swelling, fissured tongue and peripheral facial nerve palsy.3,5 we considered our patient as either purely granulomatous cheilitis or monosymptomatic form of mrs because his symptom is solely the upper lip swelling. the complete triad of melkersson-rosenthal syndrome has reportedly present in 8% to 25% of patients, and granulomatous cheilitis is the sole manifestation of the disease in 28% of cases.5 another accompanying disorder of granulomatous cheilitis is the extra-intestinal presentation of crohn’s disease.4 the differential diagnosis of persistent lip swelling includes other granulomatous diseases such as sarcoidosis, mycobacterial infection, and histoplasmosis.10 the management of granulomatous cheilitis is difficult in the absence of knowledge of its etiology. the main purpose of treatment is to improve the patient’s clinical appearance and comfort. there is no uniform consistent treatment plan or randomized, placebocontrolled trial that is cited in the literature. however, therapies with anti-inflammatory activity such as corticosteroids and immunomodulatory medications show the most promise.1 topical, intralesional, and systemic corticosteroid are all described in literature to be effective for granulomatous cheilitis, with intralesional triamcinolone widely described to be the most effective.7,11,12 immunomodulators that targets tumor necrosis factor (tnf)-α such as adalimumab have been reported to successfully cleared granulomatous cheilitis, although potential adverse effects should always be considered.10 our patient had failed systemic treatment with minocycline and metronidazole, but he noticed mild improvement with intralesional triamcinolone. nonetheless, he was reluctant to have more injections due to discomfort. we then decided to apply 10% benzocaine gel 10-20 minutes prior to injection of 20 mg/cc intralesional triamcinolone. the patient was very satisfied and compliant with this regimen. he was treated every two weeks for a total of five administrations, resulting in complete remission. granulomatous cheilitis is a rare condition with variable clinical presentation. there are various therapeutic methods described, however we believe intralesional triamcinolone injections with prior application of topical anesthetic to ease discomfort, could be an alternative treatment. discussion conclusion skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 164 conflict of interest disclosures: none funding: none corresponding author: nahla shihab, md department of dermatology, icahn school of medicine at mount sinai, new york, ny 5 e 98th street, new york, ny 10029 phone: 212-241-9728 fax: 212-987-1197 email: nahla.shihab@gmail.com references: 1. banks t, gada s. a comprehensive review of current treatments for granulomatous cheilitis. br j dermatol, 2012; 166(5): 934-7. 2. critchlow wa, chang d. cheilitis granulomatosa: a review. head neck pathol 2014; 8(2): 209-13. 3. kovich oi, cohen de. granulomatous cheilitis. dermatology online j 2004: 10(3):10. 4. van der waal rif, schulten eajm, van de scheur mr, wauters impmj, starink tm, van der waal i. cheilitis granulomatosa. j eur acad dermatol 2001: 15(6), 519-23. 5. chintagunta sr, sana sn, bukka ks, padma s. cheilitis granulomatosa: case series. j dr ntr univ health sci 2017; 6(3): 174-7. 6. nair pa, patel tm. granulomatous cheilitis involving the lower lip. egypt j dermatol venereol 2017; 37(2): 85-8. 7. el-hakim m, chauvin p. orofacial granulomatosis presenting as persistent lip swelling: review of 6 new cases. j oral maxillofac surg 2004; 62: 11147 8. gupta a, singh h. granulomatous cheilitis: successful treatment of two recalcitrant cases with combination drug therapy. case reports in dermatological medicine 2014: 1-4. 9. savas j, sokoloff d, sanchez km, lichtstein dm. granulomatous cheilitis: a stiff upper lip. cutis 2015; 96: 18-20. 10. chandra ar, mahesh s. miescher’s cheilitis: a case report with literature review. journal of pathology of nepal 2018; 8: 1313-16. 11. alajbeg i, rogulj aa, hutinec z.. orofacial granulomatosis treated with intralesional triamcinolone. acta dermatovenerol croat 2011; 19(3): 165-9. 12. bacci c, valente ml. successful treatment of cheilitis granulomatosa with intralesional injection of triamcinolone. j eur acad dermatol venereol 2010;24:363-4. mailto:nahla.shihab@gmail.com microsoft word september 2020 rescomp 923 proof.docx skin september 2020 volume 4 issue 5 copyright 2020 the national society for cutaneous medicine 408 resident competition researh article management and referral patterns in pediatric atopic dermatitis: a survey of pediatric healthcare professionals courtney n. bernett, do¹, emma hignett, bsc², pearl kwong, md, phd³ ¹department of dermatology, orange park medical center, orange park, fl ²ucf college of medicine, orlando, fl ³private practice, jacksonville, fl pediatric atopic dermatitis (ad) is a common dermatological condition, affecting ~13% of pediatric patients.1 the incidence of pediatric ad continues to increase worldwide and the consequences of inadequately managing this disease are devastating for the patient, their families, and their financial situation.2,3 health-related quality of life (qol) studies in pediatric abstract background: the incidence of pediatric atopic dermatitis (ad) has continued to increase worldwide and pediatric healthcare providers (phps) are typically the initial healthcare provider tasked with management of this disease. the consequences of inadequately managed ad and misdiagnosed food allergies are devastating for patients and their families, and the financial burden associated with these scenarios can be overwhelming. objective: to assess the management and referral patterns of pediatric ad patients by phps in the jacksonville, florida (fl) area. methods: an online electronic survey was distributed to 70 phps using surveymonkey©. data was collected over a 6-week period. the survey yielded a sample size of 28. results: most participants were physicians (92.8%), with an average of 21.75 years in practice. just over half (53%) of phps were aware of the american academy of dermatology (aad) guidelines of care for the management of ad. dermatologists were the initial referral choice for ad management in 2/3, while 1/3 indicated preference for an allergist. diet alteration was used by 14.3% as an initial ad management step and 35.7% tried elimination diets prior to referral to an allergist. referral to specialists were low with 75% phps referring <25 % of their ad patients to dermatology. conclusion: with the number of outpatient ad visits increasing amongst phps, knowledge of management guidelines, in-depth understanding of appropriate use and limitations of elimination diets and food allergen testing, and referral to specialists suitable for management of this cutaneous disorder are imperative, but found to be highly variable. introduction skin september 2020 volume 4 issue 5 copyright 2020 the national society for cutaneous medicine 409 patients with generalized ad have elucidated the profound effect this disease has on children, with the impact of ad rated only inferior to cerebral palsy, equal to chronic renal disease, and less severe than cystic fibrosis, asthma, and psoriasis.⁴ phps are usually the initial healthcare provider tasked with evaluation and management of ad. the annual number of ad visits to phps far exceeds the annual number of ad visits to dermatologists; in fact, the number of outpatient ad visits is increasing amongst pcps, but declining amongst dermatologists.5 in the course of our clinical practice as dermatologists, we often observe that pediatric ad patients receive a referral to an allergist, prior to a dermatologist, in an attempt to identify “triggers” or “causes” of ad. alternatively, the patients may not receive a referral to an allergist, but instead, extensive food allergen panels (rast) are ordered and interpreted by the php. this form of standard food allergen panel ige testing notoriously results in misdiagnosis of food allergies, leading to unjustified cessation of breastfeeding, elimination or restrictive diets, financial burden, and risk of social isolation, nutritional deficiencies, and growth retardation.⁶,⁷ the aad, national institute of allergy and infectious disease (niaid), and american academy of allergy, asthma & immunology (aaaai)/american college of allergy, asthma & immunology (acaai) joint task force all have specific guidelines for food allergy testing in moderate to severe ad patients less than 5 years old.8-10 interestingly, all parties agree that limited food allergy testing should be initiated in patients with persistent ad despite optimized medical management of their dermatosis and/or in patients with a reliable history of a type 1 hypersensitivity reaction after ingestion of a specific food.⁸,⁹ this study sought to assess phps awareness of the aad guidelines of care for the management of ad, initial treatment steps utilized by phps for ad treatment, referral preference (allergist vs dermatologist), reasons phps order allergen-specific serum ige (rast) testing, and the youngest ages they will order such testing in. the data was collected via an online, anonymous survey, generated through surveymonkey©. the survey was dispersed to actively practicing phps, including pediatricians, nurse practitioners (np), and physician assistants (pa) in the greater jacksonville, fl area via an email link (primary dispersion). the email addresses utilized in primary dispersion were acquired through years of practice and communication with local colleagues. the email body contained general survey information, including discussion of: anonymous nature of the survey, length/time commitment involved in participation, and a disclaimer that further survey submission confirmed consent of participation in the study. study participants were encouraged to share the survey link with other colleagues actively practicing pediatric medicine (secondary dispersion). the initial collection goal was 21-30 php responses over a 6-week data collection period. the email containing the survey link was dispersed by the primary investigator (pi) on 3 separate occasions over the 6week period. this study was determined to be exempt from irb oversight by the healthcare america (hca) institutional methods skin september 2020 volume 4 issue 5 copyright 2020 the national society for cutaneous medicine 410 review board (irb). this research was supported (in whole or in part) by hca healthcare and/or an hca healthcare affiliated entity. the views expressed in this publication represent those of the author(s) and do not necessarily represent the official views of hca healthcare or any of its affiliated entities. the survey was dispersed to ~70 practicing phps (primary survey dispersion). data regarding the number of additional phps who may have participated in the survey via secondary survey dispersion is unknown. a total of 31 survey responses were obtained, yielding an estimated response rate of 44.3%. the initial survey question, “do you manage the treatment of eczema or atopic dermatitis in pediatric patients?”, was used as an inclusion versus exclusion criteria tool for the study. participants who answered “yes” (28), were included in the sample size, while participants who answered “no” (2) or skipped the question (1) were excluded. physicians accounted for 92.8% (26 phps) of participants, while physician extenders, such as nps (1 = 3.6%) and pas (0), were poorly represented. one survey participant (1 = 3.6%) did not disclose their job title. the average number of years in practice was 21.75. over half (16 = 57.1%) of participants completed their residency training (physicians) or graduate school degree (nps/pas) in the southeast. of the surveyed phps, 75% saw between 6-15 patients monthly for evaluation and management of ad (table 1 and 2). just over half of phps (15 = 53.6%) reported that their management decisions were reflective of the aad guidelines regarding pediatric ad, while 13 (46.4%) indicated they were unaware of the guidelines. for initial management of pediatric ad, optimization of moisturization with emollients (27 = 96.4%), over-thecounter (otc) topical corticosteroids, such as 1% hydrocortisone (11 = 39.3%), and prescription topical corticosteroids (9 = 32.1%) were the most highly selected options. other selected initial management options included: empiric diet alteration (4 =14.3%) and allergy testing (allergenspecific serum ige or rast testing) to determine allergy triggers (1 = 3.6%) (table 3). of the 28 phps in the study, 11 providers indicated that they order and interpret allergen-specific serum ige (rast) testing in their practice. information regarding the indications for ordering testing and the youngest age groups they order testing in are displayed in figure 1. phps were also queried regarding approximately what percentage of their existing ad patient panel had rast testing. all survey participants (28) were included in this response analysis as testing may have been performed by another healthcare provider, such as an allergist; the results are as follows: 71.4% (20 phps) reported 0-25% of their patients had received testing, 17.9% (5 phps) indicated 26-50% had been tested, and 3 (10.7%) selected “n/a”. participants were asked which specialist they were most likely to refer their ad patient to for management of their disease, 9 (32.1%) chose allergy/immunology, 18 (64.3%) chose dermatology, one participant selected “other”, and no participants chose alternative medicine. the participant that indicated “other”, commented that they would choose an allergist for patients <1 results skin september 2020 volume 4 issue 5 copyright 2020 the national society for cutaneous medicine 411 table 1. job title and geographic training location of phps job title physician (md/do) nurse practitioner physician assistant unknown provider number (%) 26 (92.8%) 1 (3.6%) 0 1 (3.6%) geographic location northeast southeast midwest pacific number (%) 5 (17.9%) 16 (57.1%) 2 (7.1%) 4 (13.3%) table 2. monthly number of atopic dermatitis appointments atopic dermatitis appointments/month 3-5 patients/month 6-10 patients/month 11-15 patients/month 16+ patients/month number (%) 4 (14.3%) 13 (46.4%) 8 (28.6%) 3 (10.7%) table 3. initial management steps of pediatric healthcare providers for atopic dermatitis initial management for atopic dermatitis number (%) optimize moisturization with emollients 27 (96.4%) over the counter topical corticosteroids (1% hydrocortisone cream) 11 (39.3%) prescription topical corticosteroid 9 (32.1%) change in diet (i.e. change formulas, elimination diet for mother and/or baby, encourage breast feeding, etc.) 4 (14.3%) allergy testing (i.e. rast testing to determine the triggers for the patient) 1 (3.6%) year-old, but a dermatologist for older children. php estimates regarding the percentage of their ad patients that receive a referral to an allergist and/or dermatologist for co-management of their condition are represented in table 5. phps were also questioned about their most likely “next steps” in management if their current treatment strategies such as, dietary changes or elimination diets, topical emollients, prescription topical steroid, etc. were not controlling their patient’s ad. consistent with above responses, referral to a dermatologist was selected by 18 (64.3%), referral to an allergist by 6 (21.4%), increasing to a stronger potency topical steroid by 3 (10.7%), and addition of an oral antihistamine to the regimen by 1 (3.6%). no participants selected addition of an oral antibiotic (0%). similarly, we also assessed which therapies phps trial in ad patients prior to referral to an allergist for more extensive testing and this data is reflected in table 6. although the sample size of participants in the study was small (28), the surveyed phps had considerable experience (average years in practice = 21.75), most were physicians, and they managed a fair volume of ad patients, giving further merit to our study. with the role of the php becoming increasingly more important in ad management, we were surprised to uncover that just over half (53.6%) of phps were aware of the aad guidelines of care for management of atopic dermatitis.5 in accordance with aad management discussion skin september 2020 volume 4 issue 5 copyright 2020 the national society for cutaneous medicine 412 guidelines, most participants (96.4%) indicated they optimize moisturization with emollients as part of their initial ad management, but only 75% optimize moisturization prior to referral to an allergist. regardless of disease severity, all ad patients should receive optimal barrier care with gentle cleanser and regular use of emollients.10 in regards to topical corticosteroids, ~40% of phps indicated preference for otc topical steroids, such as 1% hydrocortisone cream, for initial ad management, while ~30% of phps chose a prescription strength topical steroid. inconsistency in opinion on “optimized medical management” of ad is pronounced between phps, dermatologists, and other specialists, particularly in regard to topical corticosteroid use, emollient counseling, and use of oral antibiotics.11,12 though not queried in the survey, steroid phobia amongst parents may influence the phps preference for an otc recommendation versus a prescription topical corticosteroid. in one study, 72.5% of parents admitted to concerns of utilizing topical corticosteroids on their child’s skin, with steroid-induced atrophy cited as the most common concern (34.5%).13 surprisingly, 35.7% of phps tried an empiric elimination diet prior to referral to an allergist and 14.3% of phps use diet alteration as one of their initial ad management steps. in regards to ad management, there has also been longstanding difference in opinion amongst pcps, allergists, and dermatologists regarding the relationship between food allergies and ad.11,14 in one previous study, food allergy was mentioned as a causative factor for ad during patient counseling by 40% of pediatricians.11 consequently, this diverts the caregiver’s attention towards finding the “cause” of the patient’s ad, rather than managing the disease state. in addition, effective ad therapy has shown to significantly reduce the number of perceived “food reactions” and overall parental concern for food allergy, further validating the aad recommendations for optimized medical management of ad prior to food allergy workup, either by the php or an allergist.8,15 food allergy prevalence has been increasing in the united states and 8% of all children are diagnosed with an allergy to at least one food. of these children with a food allergy, nearly one-third are diagnosed with multiple food allergies.16,17 allergen-specific serum ige (rast) is the most frequently ordered test by phps for the workup of food allergies, likely due to the ease of ordering and the requirement of only one needle-stick versus skin-prick-testing (spt) which requires a visit to an allergist and numerous sticks.18 although allergen-specific serum ige testing does have a high sensitivity rate, it also carries a high-false positive rate, leading to diagnosis of “allergies” that are often clinically irrelevant.6,8,16 the niaid guidelines specifically state that allergenspecific serum ige (rast) testing alone is not sufficient to diagnose a food allergy and the gold standard remains oral food challenge tests.9 however, we frequently encounter pediatric patients on longstanding dietary restrictions based solely on the results of their allergen-specific serum ige (rast) testing, leading to frustration amongst patients, parents, and clinicians. approximately 40% of phps indicated they order and interpret allergen-specific serum ige (rast) testing in their practice. skin september 2020 volume 4 issue 5 copyright 2020 the national society for cutaneous medicine 413 figure 1. serum allergen specific ige (rast) testing amongst phps skin september 2020 volume 4 issue 5 copyright 2020 the national society for cutaneous medicine 414 table 5. co-management and referral of pediatric ad patients % allergist referral for comanagement 0-25% 26-50% 76-100% 76-100% n/a number (%) 23 (82.1%) 3 (10.7%) 1 (3.6%) 0 1 (3.6%) % dermatologist referral for comanagement 0-25% 26-50% 76-100% 76-100% n/a number (%) 21 (75.0%) 5 (17.8%) 1 (3.6%) 0 1 (3.6%) utilization of this test, however, was lower than expected amongst respondents with 71.4% of phps indicating that ≤25% of their ad patients had received said testing and 20% of phps stating ≤50% of their ad patients had received testing. another study published in the journal of pediatrics sought to assess allergen-specific specific ige testing amongst phps and found that in mild ad, testing was ordered in 15.8% of patients and in 60.4% of moderate-to-severe patients.¹² based on epidemiological studies, approximately 2/3 of ad patients have “mild disease”, where the other 1/3 have “moderateto-severe disease”.17 assuming ad patients in our area follow a similar epidemiological distribution of severity, the frequency of allergen-specific serum ige (or rast) testing among our surveyed phps would be fairly consistent with those in the aforementioned study.12,17 the surveyed phps most frequently order allergen-specific serum ige (rast) for the following indications: recalcitrant ad despite optimized management of skin disease (63.6%) and history of a type 1 hypersensitivity reaction after ingestion of specific foods (54.5%). promisingly, this reflects that phps are testing for comorbid food allergies as recommended by the aad, niaid, and aaaai/acaai joint task force. 810 of more concern though, ~20% of phps indicated they would order testing if requested by the patient’s parents or caregiver and ~30% order testing for a patient with a strong family history of food allergies. the two aforementioned indications are not supported in the literature and may reflect the extraneous pressure placed on phps by caregivers. although allergen-specific serum ige (rast) is the preferred initial diagnostic test for food allergy workup, a fair number of phps may be ordering these expensive tests for unjustified indications. previous studies have revealed that this form of unjustified food allergen panel screening yields a positive predictive value of ≤ 3%.⁶ table 6. therapies trialed by phps prior to allergist referral therapies trialed before allergist referral number (%) prescription topical corticosteroid 25 (89.3%) gentle cleansers and emollients 21 (75.0%) otc topical corticosteroid 18 (64.3%) oral antihistamine 14 (50.0%) elimination diets 10 (35.7%) topical immunomodulators (e.g. tacrolimus/pimecrolimus) 5 (17.9%) topical crisaborole ointment 4 (14.3%) oral steroids 1 (3.6%) dupilumab 0 although no published guidelines exist regarding optimal age for allergen-specific serum ige testing, the utility of testing broad food allergen panels prior to food introduction is believed to be poor.6 interestingly, many authors have hypothesized that the origin of ige antibody development against food skin september 2020 volume 4 issue 5 copyright 2020 the national society for cutaneous medicine 415 proteins in pediatric ad patients is secondary to percutaneous absorption of food antigens through the dysfunctional cutaneous barrier. 19,20 this further emphasizes the utmost importance of early, aggressive barrier restoration in ad patients to prevent percutaneous sensitization from even occurring. in regards to referrals for ad management, our data revealed that approximately 2/3 of phps select dermatologists as the initial referral, whereas 1/3 chose allergists. with the knowledge that effective and consistent therapy for ad can alleviate food allergy concerns amongst parents, one could make the argument that all ad referrals should initially be to a dermatologist for a trial of optimized medical management.15 the caveat of this statement involves patients with any evidence of a food-induced type 1 hypersensitivity reaction, patients requiring oral food challenge testing, or in patients with associated comorbidities such as asthma; in these cases, allergy referral is undeniably indicated. overall, our data suggested referral to specialists was low amongst surveyed phps, with 75% of participants indicating ≤25% of their ad patients receive a dermatology referral and 82% indicating ≤25% receive an allergist referral. saavedra et al found that 52% of mild ad patients and 60% of severe patients receive a referral to a dermatologist, whereas 32% of mild ad patients and 38% of severe patients receive a referral to an allergist. our data may represent a true referral pattern in our community or a significant source of recall bias in our study.¹⁸ several limitations were identified in our study including the small sample size (28), participants were limited largely to the greater jacksonville, florida area, and lack of diversity amongst the surveyed phps with mostly physicians responding to the survey (92.8%). the lack of responses from nps and pas is particularly significant since physician extenders also play a large role in the management and care of pediatric atopic dermatitis patients. some of the study participants may have also felt more compelled to complete the survey since they personally knew the researchers involved in the study, which may have increased the sample size. completion of this study on a broader geographical scale with increased representation of physician extenders may reveal different management and referral patterns in this subset of patients. a large proportion of ad patients are managed directly by phps and knowledge of management guidelines, appropriate use and limitations of allergen-specific serum ige (rast) testing, and proper specialist referrals are crucial. although opinion differs greatly amongst specialists, ad is a cutaneous disease and the role of food allergens in maintenance or flares of this disease is likely minimal.6,11,12 in the absence of evidence of a type 1 hypersensitivity response, initial referral of ad patients should be to a dermatologist for optimized medical management of ad. the results of this survey highlight multiple misconceptions about ad and its relation to food allergies and provides a true educational opportunity to realign the management decisions of our pediatric colleagues with current recommendations. abbreviations: fl – florida, hca – healthcare america, ad – atopic dermatitis, pcps – primary care providers, php – pediatric healthcare provider, aad – american academy of dermatology, rast – radioallergosorbent testing, qol – quality of life, niaid – national institute of allergy and infectious disease, aaaai – american academy of allergy, asthma & immunology, acaai – american college of allergy, asthma & immunology, np – nurse practitioner, pa – physician assistant, pi – primary investigator, irb – institutional review board, otc – over-the-counter, spt – skin prick testing conclusion skin september 2020 volume 4 issue 5 copyright 2020 the national society for cutaneous medicine 416 conflict of interest disclosures: none funding: this research was supported (in whole or in part) by hca healthcare and/or an hca healthcare affiliated entity. the views expressed in this publication represent those of the author(s) and do not necessarily represent the official views of hca or any of its affiliated entities. corresponding author: courtney n. bernett, do parks dermatology – ormond beach 400 lakebridge plaza ormond beach, fl 32174 phone: 386-677-9044 fax: 386-677-3083 email: courtneywilk@pcom.edu references: 1. refs silverberg ji, simpson el. associations of childhood eczema severity: a us population-based study. dermatitis. 2014;25(3):107–114. doi:10.1097/der.0000000000000034 2. flohr c, mann j. new insights into the epidemiology of childhood atopic dermatitis. allergy. 2014;69(1):3–16. doi:10.1111/all.12270 3. druker, am, wang ar,, li wq, et al. the burden of atopic dermatitis: summary of a report for the national eczema association. j invest dermatol. 2017;137(1):26-30. doi: https://doi.org/10.1016/j.jid.2016.07.012 4. beattie*, p. and lewis-jones, m. (2006), a comparative study of impairment of quality of life in children with skin disease and children with other chronic childhood diseases. british journal of dermatology, 155: 145-151. doi:10.1111/j.13652133.2006.07185.x 5. singh p, silverberg ji. outpatient utilization patterns for atopic dermatitis in the united states [published online ahead of print, 2019 mar 15]. j am acad dermatol. 2019;s0190-9622(19)30435-9. doi:10.1016/j.jaad.2019.03.021 6. bird ja, crain m, varshney p. food allergen panel testing often results in misdiagnosis of food allergy. j pediatr. 2015;166(1):97–100. doi:10.1016/j.jpeds.2014.07.062 7. fleischer dm, burks aw. pitfalls in food allergy diagnosis: serum ige testing. j pediatr. 2015;166(1):8–10. doi:10.1016/j.jpeds.2014.09.057 8. sidbury r, tom wl, bergman jn, et al. guidelines of care for the management of atopic dermatitis: section 4. prevention of disease flares and use of adjunctive therapies and approaches. j am acad dermatol. 2014;71(6):1218–1233. doi:10.1016/j.jaad.2014.08.038 9. niaid-sponsored expert panel, boyce ja, assa'ad a, et al. guidelines for the diagnosis and management of food allergy in the united states: report of the niaid-sponsored expert panel. j allergy clin immunol. 2010;126(6 suppl):s1–s58. doi:10.1016/j.jaci.2010.10.007 10. eichenfield lf, ahluwalia j, waldman a, borok j, udkoff j, boguniewicz m. current guidelines for the evaluation and management of atopic dermatitis: a comparison of the joint task force practice parameter and american academy of dermatology guidelines. j allergy clin immunol. 2017;139(4s):s49–s57. doi:10.1016/j.jaci.2017.01.009 11. resnick sd, hornung r, konrad tr. a comparison of dermatologists and generalists. management of childhood atopic dermatitis. arch dermatol. 1996;132(9):1047–1052. 12. saavedra jm, boguniewicz m, chamlin s, et al. patterns of clinical management of atopic dermatitis in infants and toddlers: a survey of three physician specialties in the united states. j pediatr. 2013;163(6):1747–1753. doi:10.1016/j.jpeds.2013.06.073 13. charman cr, morris ad, williams hc. topical corticosteroid phobia in patients with atopic eczema. br j dermatol. 2000;142(5):931–936. doi:10.1046/j.1365-2133.2000.03473.x 14. thompson mm, tofte sj, simpson el, hanifin jm. patterns of care and referral in children with atopic dermatitis and concern for food allergy. dermatol ther. 2006;19(2):91–96. doi:10.1111/j.15298019.2006.00062.x 15. thompson mm, hanifin jm. effective therapy of childhood atopic dermatitis allays food allergy concerns. j am acad dermatol. 2005;53(2 suppl 2):s214–s219. doi:10.1016/j.jaad.2005.04.065 16. jackson kd, howie ld, akinbami lj. trends in allergic conditions among children: united states, 1997-2011. nchs data brief. 2013;(121):1–8. 17. gupta rs, springston ee, warrier mr, et al. the prevalence, severity, and distribution of childhood food allergy in the united states. pediatrics. 2011;128(1):e9–e17. doi:10.1542/peds.2011-0204 18. sicherer sh, wood ra; american academy of pediatrics section on allergy and immunology. allergy testing in childhood: using allergen-specific ige tests. pediatrics. 2012;129(1):193–197. doi:10.1542/peds.2011-2382 19. tham eh, leung dy. mechanisms by which atopic dermatitis predisposes to food allergy and the atopic march. allergy asthma immunol res. 2019;11(1):4–15. doi:10.4168/aair.2019.11.1.4 20. strid j, hourihane j, kimber i, callard r, strobel s. disruption of the stratum corneum allows potent epicutaneous immunization with protein antigens resulting in a dominant systemic th2 response. eur j immunol. 2004;34(8):2100–2109. doi:10.1002/eji.200425196 skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 797 research letter the prevalence of secondhand smoke exposure in hidradenitis suppurativa: a cross-sectional survey study sydney a. weir, msph1, hana ahmed md2, mia broughton, md2, lauren c.s. kole, md2 1 marnix e. heersink school of medicine, the university of alabama at birmingham, birmingham, al 2 department of dermatology, the university of alabama at birmingham, birmingham, al hidradenitis suppurativa (hs) is a chronic inflammatory disease of the skin associated with several risk factors, including genetic susceptibility, obesity, and firsthand smoking.1,2 firsthand smoke is the smoke inhaled directly by the person using tobacco products, including cigarettes, cigars, pipes, hookahs, and vaping devices.3 while firsthand smoking is highly prevalent in patients with hs4, secondhand smoke, defined as the inhalation of smoke from burning a tobacco product or smoke that is exhaled by smokers,5 and its relationship to hs has not been assessed. this study aims to determine the prevalence of secondhand smoke exposure among a sample of hs patients. this is a cross-sectional study, and data collection occurred from december 1, 2021, to may 31, 2022. a survey was distributed to patients at the university of alabama at birmingham general and pediatric dermatology clinics who were diagnosed with abstract introduction: hidradenitis suppurativa (hs) is a chronic inflammatory disease of the skin highly associated with firsthand smoking. secondhand smoke, defined as the inhalation of smoke from burning a tobacco product or smoke that is exhaled by smokers, and its relationship to hs has not been assessed. this study aims to determine the prevalence of secondhand smoke exposure in the hs population. methods: in this cross-sectional study (n=136), surveys were both administered in a dermatology clinic and emailed to patients with hs, verruca vulgaris (vv), and atopic dermatitis (ad). control groups were selected based on secondhand smoke associations: ad has a known association, whereas vv does not. results: the survey response rate was 67.3% (n=136). we found that more than half of hs patients (58.73%) were exposed to secondhand smoke within the last 12 months, whereas 38.30% and 30.77% in the ad and vv groups were exposed, respectively (p=0.0209). however, our data did not identify a significant correlation between secondhand smoke and hs disease severity. conclusion: our study is the first to assess the prevalence of secondhand smoke exposure in the hs population. although we observed a statistically significant increased prevalence of secondhand smoke in hs patients, we could not establish how it may affect severity of disease. our study highlights an area for further investigation evaluating the relationship between passive tobacco exposure and inflammatory skin disease. skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 798 hs, atopic dermatitis (ad), or verruca vulgaris (vv) by a dermatologist and who were aged 14+. additionally, surveys were also emailed to participants based on retrospective diagnosis. control groups were selected based on secondhand smoke associations: ad has a known association, whereas vv does not. in terms of definitions, hs severity (mild, moderate, or severe) was self-reported by participants based on descriptions provided in the survey, and active secondhand smoke exposure was defined as the inhalation of smoke from a tobacco product exhaled by another person within the last 12 months. statistical analyses were performed using jmp pro 16 at α=0.05 significance level. the survey response rate was 67.3% (n=136). most hs patients (53.97%) reported having moderate hs defined as having ‘recurrent abscesses and nodules with tracts or scarring’ (table 1). there was no significant difference between smoking status (i.e., never smoker, past smoker) among the three skin condition groups (p=0.1813). additionally, 51.5% of the total sample reported one or more household members being smokers during their childhood, with no significant differences between skin condition groups (p=0.2448). more hs patients reported experiencing active secondhand smoke exposure (defined as tobacco exposure within the last 12 months) than those with ad and vv (p=0.0209, table 1). although hs patients more likely reported secondhand smoke exposure than other groups, there was no difference in self-reported hs disease severity among those with secondhand smoke exposure and those without (p=0.2419). in summary, our study found that a majority of hs patients (58.7%) were exposed to secondhand smoke. compared to patients with ad and vv, hs patients had significantly higher rates of secondhand smoke exposure; however, there was no significant correlation between secondhand smoke and hs disease severity. research illustrates that tobacco smoke promotes proinflammatory cytokines and various inflammatory pathways in hs lesions that contribute to disease progression.1 based on the knowledge of how smoking tobacco affects chronic inflammatory skin diseases such as ad and hs, it is possible that significant secondhand smoke exposure can act similarly. while data on the effects of passive smoke exposure on hs is currently limited, our results identify the increased prevalence of secondhand smoke in hs. while smoking cessation can lead to improved outcomes4, more research is needed to evaluate whether complete smoke avoidance would be effective and reasonable for hs patients. this is an essential consideration in the pediatric population, who have little to no control over the smoke exposure they receive in the household. this single-center study was limited by a small sample size and significant differences between groups which impacted the ability to compare and draw conclusions about secondhand smoke exposure. additionally, several variables that may influence secondhand smoke prevalence, including race, socioeconomic factors, and age,6 were not accounted for and may have confounded the results. according to the centers for disease control and prevention, secondhand smoke exposure is more table 1. survey data by skin condition (n=136) skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 799 characteristic hs (n=63) n (%) ad (n=47) n (%) vv (n=26) n (%) p-value age (years) mean ± sd 36 ± 10.67 47 ± 19.67 45 ± 17.87 0.0007 med, min-max 36, 15-66 48, 17-90 43, 18-84 sex assigned at birth female 55 (87.30) 34 (72.34) 15 (57.69) 0.0083 male 8 (12.70) 13 (27.66) 11 (42.31) race/ethnicity black 43 (68.25) 16 (34.04) -<0.0001 white 17 (26.98) 27 (57.45) 23 (88.46) hispanic/latino 1 (1.59) 1 (2.13) - asian 1 (1.59) 2 (4.25) 1 (3.85) biracial/multiracial 1 (1.59) 1 (2.13) 2 (7.69) selfreported hs severity mild 6 (9.52) moderate 34 (53.97) severe 23 (36.51) frequency of hs flares ≥ 3 times a month or never completely clear 22 (34.92) 1-2 times a month 15 (23.81) every couple of months 18 (28.57) 2-3 times a year 7 (11.11) once every year or every couple of years 1 (1.59) smoking status never smoker 41 (65.08) 34 (72.34) 18 (69.23) 0.1813 past smoker 9 (14.29) 8 (17.02) 7 (26.92) skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 800 *frequency of secondhand smoke exposure was only evaluated in participants who reported active secondhand smoke exposure. thus, for hs n=36 (missing n=1), for ad n=18, and for vv n=8. hs= hidradenitis suppurativa, ad= atopic dermatitis, vv= verruca vulgaris common among children ages 3-11 years, non-hispanic black americans, and those living below the poverty level.6 despite these limitations, our findings suggest that secondhand smoke exposure is more prevalent in hs patients than in those with atopic dermatitis or verruca vulgaris. while we cannot conclude if secondhand smoke is truly increased in hs patients regardless of race or other potential confounders, this raises the question if screening for secondhand smoke exposure in the hs population would have clinical value. further research is needed to assess if an association exists between hs and secondhand smoking. conflict of interest disclosures: none funding: none corresponding author: lauren c.s. kole, md 500 22nd st s floor 3 birmingham, al 35233 e-mail: laurenkole@uabmc.edu current smoker 13 (20.63) 5 (10.64) 1 (3.85) childhood secondhand smoke exposure yes, 1 or more people in my house were smokers 34 (53.97) 25 (53.19) 11 (42.31) 0.2448 yes, many people around me smoked (but the people in my household did not smoke 15 (23.81) 9 (19.15) 3 (11.54) no, i had little to no second hand smoke exposure as a child 14 (22.22) 13 (27.66) 12 (46.15) secondhand smoke exposure in last 12 months yes 37 (58.73) 18 (38.30) 8 (30.77) 0.0209 no 26 (41.27) 29 (61.70) 18 (69.23) frequency of secondhand smoke exposure* a couple of times a month 14 (38.89) 10 (55.56) 4 (50.00) - 1-2 times per week 1 (2.78) 2 (11.11) - every couple of days 3 (8.33) 2 (11.11) 1 (12.50) 1-2 times per day 2 (5.56) 2 (11.11) 2 (25.00) every couple of hours 16 (44.44) 2 (11.11) 1 (12.50) skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 801 references: 1. bukvic mokos z, miše j, balic a, marinovic b. understanding the relationship between smoking and hidradenitis suppurativa. acta dermatovenerol croat. 2020;28(1):9-13. 2. miller im, mcandrew rj, hamzavi i. prevalence, risk factors, and comorbidities of hidradenitis suppurativa. dermatol clin. 2016;34(1):7-16. doi:10.1016/j.det.2015.08.002 3. tobacco stops with me tswm. differences & dangers of first, second & thirdhand smoke. tobacco stops with me. https://stopswithme.com/first-second-andthirdhand-smoke-the-differences-anddangers/#:~:text=it's%20not%20a%20term%20y ou,have%20been%20documented%20for%20de cades. published january 3, 2022. accessed march 27, 2023. 4. vossen arjv, van der zee hh, onderdijk aj, boer j, prens ep. hidradenitis suppurativa is not associated with the metabolic syndrome based on body type: a cross-sectional study. j dermatol. 2017;44(2):154-159. doi:10.1111/1346-8138.13572 5. nci dictionary of cancer terms. national cancer institute. https://www.cancer.gov/publications/dictionaries/ cancer-terms/def/secondhand-smoke. published 2022. accessed july 14, 2022. 6. centers for disease control and prevention. health effects of secondhand smoke. health effects of secondhand smoke. https://www.cdc.gov/tobacco/data_statistics/fact_ sheets/secondhand_smoke/health_effects/index. htm. published june 14, 2021. accessed november 3, 2022. microsoft word noninvasive body contouring.doc skin july 2017 volume i issue i copyright 2017 the national society for cutaneous medicine 18 in-depth reviews noninvasive body contouring: literature review and summary of objective data bernstein daniel mda; farberg aaron s mda; khorasani hooman mda; kriegel david mda adepartment of dermatology, division of dermatologic and cosmetic surgery, mount sinai school of medicine, new york, new york capsule summary: • noninvasive body contouring devices vary by efficacy, treatment schedule and safety profile. • this review compares body contouring modalities, allowing for quick comparison between modalities. • this review enables the selection of a body contouring modality that best suits each specific patient’s goals, availability and aversion to risk. abbreviations: cryo: cryolipolysis; fus: focused ultrasound; rf: radiofrequency; lllt: low level laser therapy; hifu: high intensity focused ultrasound; lofu: low intensity focused ultrasound background: there is increasing demand for noninvasive body contouring but objective data is difficult to compare between modalities. currently, the most accepted forms of noninvasive body contouring are cryolipolyisis (cryo), focused ultrasound (fus), radiofrequency (rf), and low level laser therapy (lllt). objective: to summarize the objective data on noninvasive body contouring. methods: in october 2016, a pubmed search was performed with terms “noninvasive body contouring” or “non-invasive body contouring.” the search was limited to human studies in english on the four major modalities. results: 55 articles yielded data from 3649 patients. the most well studied modality was cryo and the least was rf. decreased abdominal/flank localized adiposity was most the most common endpoint reported. both the minimum and maximum reported decreases in abdominal girth were from studies using rf (1.4cm and 7.4cm, respectively). side effects were most common and significant with cryo and absent with lllt. conclusions: noninvasive body contouring has a significant amount of objective data available in the literature to date. reductions of localized adiposity are clinically and statistically significant but modest. to date, the best reported positive results have been obtained with rf and the lowest risk of side effects is with lllt.   abstract skin july 2017 volume i issue i copyright 2017 the national society for cutaneous medicine 19 cosmetic procedures targeting excess fat have evolved over the past 30 years to be less invasive. unfortunately, objective studies comparing modalities for noninvasive body contouring are limited, which hampers physicians and patients alike when choosing an appropriate treatment device. there are four major modalities for noninvasive body sculpting: cryolipolysis (cryo), radiofrequency (rf), focused ultrasound (fus) and low level laser therapy (lllt) 1-7. fus is subdivided into high intensity focused ultrasound (hifu) and low intensity focused ultrasound (lofu). each modality varies by treatment schedule, onset of results, and side effect profile. furthermore, results are reported in multiple ways, from circumference measurements to diagnostic ultrasound of fat thickness. this review of the published peer-reviewed literature presents and summarizes the objective data of the four major noninvasive modalities for comparison. in october of 2016, a pubmed search was performed with terms “noninvasive body contouring” and “non-invasive body contouring.” the search was limited to human studies in english. the scope was limited to objective data reported on cryo, fus, rf and lllt. a total of 58 articles were found, the abstracts were screened, and all remaining articles were thoroughly read. pertinent sources cited by these articles were also obtained and read. 55 articles were within scope and reported data from 3649 patients (table 1). the modality with the least total study participants was rf (280 patients, 10 studies). the most studied modality was cryo (1407 patients, 15 studies). decreased localized abdominal/flank adiposity was the most consistently reported outcome across all studies, with minimum (1.4cm)8 and maximum (7.4cm)9 decreases both reported by rf studies (figure 1). cryo did not report results using girth as a metric but reported 19.6-25.5% decreased abdominal/flank fat thickness when measured by ultrasound10-11. one rf study reported 29% decreased abdominal/flank fat thickness by ultrasound8. two studies reported results that were not statistically significant, one using fus12 and the other using lllt13. almost all reported side effects were mild and transient. the most commonly reported side effect was pain (often reported as patient comfort). no pain was reported in all lllt studies and 2 studies evaluating rf14-15 (figure 2). side effects were most common with cryo, followed by rf and fus. to avoid side effects, comparable results were often obtained via multiple, lower energy treatments. reported patient satisfaction rates varied by modality (figure 3) and body location. the one non-transient side effect reported was paradoxical adipose hyperplasia (pah) associated with cryo. this rare adverse event was reported 4 times in the articles reviewed16-17. some estimates of incidence are 1:20,00016 but may be as high as 1:20017.                         introduction methods results skin july 2017 volume i issue i copyright 2017 the national society for cutaneous medicine 20   figure 1: average decreased abdominal circumference. data pooled from all studies. cryo did not report girth measurements. figure 2: patient comfort/lack of pain. data pooled from all studies. ** all studies using lllt had no pain. figures skin july 2017 volume i issue i copyright 2017 the national society for cutaneous medicine 21 figure 3: patient satisfaction. data pooled from all studies. **results from elm et al not statistically significant, 0% patient satisfaction. figure 4: hifu: average decreased waist circumference21-24. (a)abdomen only, (af)abdomen +/flanks, (af)abdomen and flanks. *all studies had oxford cebm level of evidence 2b except fatemi et al (level 4). skin july 2017 volume i issue i copyright 2017 the national society for cutaneous medicine 22 figure 5: lofu: average decreased waist circumference12, 26-30. (*)average of multiple treatment areas, (**)unique lofu device, (***)results not statistically significant. all studies had oxford cebm level of evidence 2b. figure 6: rf: average decreased abdominal circumference8-9, 14-15, 35-37, 40. (ve)velashape, (e)endymed, (va)vanquish, (t)tripollar. (*)treatment included abdomen and flanks. all studies had oxford cebm level of evidence 2b. skin july 2017 volume i issue i copyright 2017 the national society for cutaneous medicine 23 figure 7: cryo: average caliper decrease by location10, 18, 44-45. (o)average of multiple areas, (a)abdomen only, (f)flanks only, (a/f)abdomen and/or flanks only, (k)knees, (t)thigh. *all studies had oxford cebm level of evidence 2b except garibyan et al (level 1b). figure 8: cryo: average decreased trunk adipose thickness10-11, 18, 44. (a)abdomen only, (f)flanks only, (a/f)abdomen and/or flanks only, (f/b)flanks or back. *all studies had oxford cebm level of evidence 2b except garibyan et al (level 1b). skin july 2017 volume i issue i copyright 2017 the national society for cutaneous medicine 24 figure 9: cryo: average decreased thigh adipose thickness51-53 measured by ultrasound. all studies had oxford cebm level of evidence 2b.     figure 10: lllt: average decreased girth by location55-56, 58-59, 62. (*)results not statistically significant. oxford cebm level of evidence 1b for jackson et al 2009, elm et al and caruso-davis et al. oxford cebm level of evidence 2b for jackson et al 2012 and mcrae et al.       skin july 2017 volume i issue i copyright 2017 the national society for cutaneous medicine 25 noninvasive modality human studies total patients prospective patients cryo 13 1407 394 fus 11 973 831 rf 10 280 266 lllt 7 989 209 table 1: overall breakdown of studies and patients included in this review. cryo fus:hifu fus:lofu rf lllt device(s) studied coolsculpting liposonix ultrashape velashape, 3deep, vanquish, thermismooth, tripollar zerona, lapex mechanism freezing thermal non-thermal thermal non-thermal treatment schedules once once every 4 weeks every 1-2 weeks 3 times per week treatments 1 1 3 4-6 6 visit duration (minutes) 60 45-60 30-90 35-45 40 onset (weeks) 8 4 2 1 1 expected results (weeks) 24 12 12 4-16 2 decreased abdominal girth (centimeters) n/a 2.1-4.15 2.15-4.7 1.4-7.4 2.15-2.89 table 2: data summarized from all four major modalities of noninvasive body contouring. tables skin july 2017 volume i issue i copyright 2017 the national society for cutaneous medicine 26 table 2 summarizes treatment schedules and results by modality. patient goals should guide appropriate selection of modality. some patients may request a single treatment while others may prefer minimal downtime, etc. of note, cryo is reported to have diminishing returns with successive treatments18, while other modalities are associated with progressive, cumulative results. to further guide appropriate modality selection, each modality will be assessed below. fus subdivisions of fus are hifu (thermal lipolysis) and lofu (mechanical cavitation)1920. hifu was studied via liposonix (solta)21-25, with reported results within 4 weeks of a single treatment23-24. each treatment took under an hour and multiple passes were delivered over a localized area. the hifu device was studied on the abdomen and flank only (figure 4). redness, pain, swelling, and bruising were common side effects with treatment. altered sensation and formation of subcutaneous nodules were found in some patients, but all reported side effects were transient. lofu was studied primarily via ultrashape contour i (syneron/candela) 26-29. results were seen as early as 2 weeks26, 29 but 3 treatments were typically performed. each treatment session took 30-90 minutes, depending on the area(s) targeted. the device was studied on the abdomen26, 28-29, flanks26, 28-29, thighs28-29, knees28 and chest/breast28. figure 5 summarizes lofu results on the waist. the most common side effects were redness and pain. rarely, blisters and bruising occurred. in particular, lofu penetrates deeper than hifu and superficial bones (iliac crest) may reflect energy and cause blisters12. for this reason, caution should be used over areas with superficial bony structures. in addition, one study with a high dropout rate (only 11/53 subjects returned for follow-up evaluation) failed to find statistically significant results. the lack of follow-up may have significantly decreased the study’s power12. rf many rf devices have been studied to date and review articles specific to rf have been published31-34. the velashape (syneron/candela)8-9, 35, 3deep (endymed)14, 15, vanquish (btl)36-37, thermismooth 250 (thermi/almirall)38 and tripollar (pollogen/lumenis)39-40 systems all had objective, clinical data on humans. treatment regimens were similar amongst them but results were variable, which may be due to the small sample of patients studied. onset was appreciable within a week14 but multiple treatments were often performed. the abdomen8-9, 14-15, 35-37, 40, flanks8-9, 14-15, 3537, 40, buttocks8-9, 40, thighs8-9, 14, 39-40, arms35 and face32 were all studied with rf for body contouring. reported rf results on abdominal girth are presented in figure 6. transient redness and swelling were expected side effects, with most studies reporting both in 100% of patients. velashape had some reports of bruising and burns as well8-9, 35. cryo the main cryo device investigated was coolsculpting (zeltiq)10-11, 18, 41-54, which has also had review articles published specific to the modality41-43. only one treatment was usually necessary but diminishing returns with additional treatments were reported18 and onset took about 8 weeks11, 44. in addition to the abdomen10, 18, 45-46, flank10-11, 18, 44-48, buttocks45 and back10, 45-46, specific applicators exist for the arms50, knees10, 45 and thighs10, 45-46, 49-52. despite these adaptations, reported results on the trunk discussion skin july 2017 volume i issue i copyright 2017 the national society for cutaneous medicine 27 tended to exceed those of the extremities10, 45(figures 7, 8, 9). redness, swelling, tissue infiltration and mild pain were expected transient side effects, while bruising was much less common. almost all patients experienced some degree of altered sensation after treatment. most were limited to numbness but the effects lingered up to 6 weeks11. unfortunately, there were some reports of pah, which is thought to be permanent and occurred 2-12 months after treatment16-17. the incidence of pah is estimated to be 1:20,000 treated patients16 but may be as high as 1:20017 and may occur in higher proportions of men16. over 30 cases have been reported to date. lllt lllt has been separately reviewed as a modality53 and was investigated via zerona (erchonia)54-60 and lapex 2000 (meridian)61. treatments were studied on the abdomen5455, 57-58 flanks54-55, 57, 58, buttocks54, 57-58, thighs54-55, 57-58 and arms56, 59-60. six of the seven studies published on lllt for body contouring used the zerona device, with treatments 3 times per week for 2 weeks and results first noted at 1 week59. the lapex 2000 was used twice a week for 4 weeks and yielded results at 2 weeks61. while the results were modest compared to other modalities (figure 10), there were absolutely no side effects reported. however, one study55 failed to report significant results. it was noted that the study was very small (only 5 patients) and was only applied to partial body sites. since lllt may involve mobilizing released fat for systemic metabolism, broader application of the laser light may be relevant. furthermore, jackson et al57reported decreases in girth at untreated sites, supporting a systemic mechanism. still, the study was retrospective and those patients that volunteered to share their experience are may be those with superior results. combinations combination devices are available, two of which were investigated. ultrashape rfvac (syneron/candela)62 combined hifu and rf technology while proshockice (promoitalia)63 combined acoustic shock wave therapy and cryo. chang et al62 studied ultrashape rfvac on 32 patients with treatments every 2 weeks for 3 treatments. average results yielded 3.91cm decreased abdominal circumference at 1 month follow-up and the results were durable up to 1 year later64. ferraro et al63 studied 50 patients using proshockice every 15 days for 3-4 treatments and reported 6.86cm average decreased abdominal circumference. while it is possible that the diminishing returns of cryo could be mitigated by additional, simultaneously applied modalities, the small sample size must be taken into account and further studies should be completed for confirmation. limitations variability of reported endpoints was the main limitation. comparing circumference measurements to ultrasound or caliper measurements was not straight forward65. some endpoints combined multiple treatment areas into a single large measurement, which may include bilateral areas or the summation of multiple, distinct treatment areas. flank results were grouped with the abdomen or back, depending on the study. the waist or hips represented any combination of the abdomen, back and/or flanks. additional problems existed with variability in study protocols. not all studies required patients to abstain from diet and exercise and those that did tracked weight changes as a marker of compliance. unfortunately, small fluctuations in weight could correspond to unpredictable changes in body contour. skin july 2017 volume i issue i copyright 2017 the national society for cutaneous medicine 28 another limitation was the high percentage of retrospective study patients (53%). retrospective studies tended to report better results and may underestimate complications due to selection bias. this study is also limited by scope and search terms. there are more devices than those described in this review that have been studied by other means. nevertheless, patients and physicians don’t necessarily need to be precise and accurate when it comes to body contouring. ultimately, patients and physicians are looking for improvement in body contour without significant risk. as such, patient satisfaction and paucity of side effects may be more important than clear cut, drastic results. if such results are desired, abdominoplasty and liposuction are options. future studies/devices a formal meta-analysis is needed for each modality so results can be combined and compared. the field of noninvasive body contouring is growing and many new devices are on the horizon. one recently introduced device is sculpsure (cynosure). sculpsure is a new type of laser, which reportedly causes lipolysis rather than inducing transient micropores in adipocytes. well-designed multi-center studies will be required to evaluate this (and other) new technology, so that patients and clinicians can optimize results. noninvasive body contouring is a growing field, projected to accrue more objective, peer-reviewed data with each passing year. while modalities vary by mechanism and side effects, reductions of localized adiposity are generally mild but clinically and statistically significant. not unsurprisingly, the modalities with the least risky side effect profiles were associated with the most modest reductions in localized fat. while it is unlikely that noninvasive devices will ever rival their surgically invasive counterparts, it is equally apparent that the side effect profiles of noninvasive procedures are likely to remain superior to invasive surgery. most importantly, patients and physicians must discuss specific goals, both long term and short term, when deciding the best course of treatment for body contouring. to date, reported positive results for noninvasive body contouring have been most noticeable via rf while lllt has reported the lowest risk of side effects. conflict of interest disclosures: none. funding: none. corresponding author: daniel bernstein 234 e 85th street, 5th floor new york, ny 10028 (p) 212-731-3311 (f) 212-731-3395 bernstd@gmail.com references: 1) afrooz pn, pozner jn, dibernardo be. noninvasive and minimally invasive techniques in body contouring. clin plast surg. 2014 oct;41(4):789-804. 2) jalian 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(192.9) 1 0.5 (0–2.9) psa 202 (77.8) 0 0.0 211 (81.1) 0 0.0 non-psa pspa 84 (19.1) 0 0.0 81 (18.8) 0 0.0 all axspac 570 (164.6) 1 0.6 (0.0–3.4) 363 (93.0) 1 1.1 (0.0–6.0) nr-axspa 95 (21.5) 0 0.0 97 (22.2) 1 4.5 (0.1–25.1) as 475 (143.1) 1 0.7 (0.0–3.9) 266 (70.8) 0 0.0 rheumatoid arthritis 2687 (1136.5) 0 0.0 1154 (481.1) 0 0.0 uveitis 119 (64.4) 0 0.0 120 (47.4) 0 0.0 hidradenitis suppurativa 419 (103.1) 0 0.0 366 (85.8) 0 0.0 adult psoriasis 1594 (461.2) 0 0.0 727 (206.0) 0 0.0 all jiad 99 (38.7) 0 0.0 80 (28.6) 0 0.0 aall adaand pbo-treated adult and pediatric pati ents in all interventi onal studies excluding crohn’s disease and ulcerati ve coliti s. ball adaand pbo-treated pati ents in all interventi onal studies of psa, non-psa pspa, nr-axspa, and as. call adaand pbo-treated pati ents in all interventi onal studies of nr-axspa and as. dall adapati ents in all interventi onal studies of pjia and peds era. ibd = infl ammatory bowel disease; pbo = placebo; ada = adalimumab; pys = pati ent years; aes = adverse events; ir = incidence rates; ci = confi dence interval; spa = spondyloarthriti s; psa = psoriati c arthriti s; pspa = non-psa peripheral spondyloarthriti s; axspa = axial spondyloarthriti s; nr-axspa = non-radiographic axspa; as = ankylosing spondyliti s; pjia = polyarti cular juvenile idiopathic arthriti s; peds era = pediatric enthesiti s-related arthriti s. • overall, the incidence rate for ibd events in ada-treated pati ents during pbo-controlled periods and open-label extensions across all interventi onal trials included in this analysis was 0.1/100 pys (table 3) • the rates of ibd events varied across therapeuti c indicati ons from <0.1 to 0.8/100 pys background • adalimumab (ada) is approved for the treatment of crohn’s disease (cd) and ulcerati ve coliti s (uc); therefore, it is postulated that new onset or fl are of infl ammatory bowel disease (ibd) is a rare occurrence in ada clinical trials for non-ibd indicati ons objective • the purpose of this analysis was to determine the rates of ibd adverse events (aes) in ada clinical trials, parti cularly in spondyloarthriti s (spa) pati ents who are at a higher risk of ibd as a feature of spa incidence of infl ammatory bowel disease events in adalimumab clinical trials across indicati ons jeff rey r curti s1, dirk elewaut2, su chen3, maja hojnik4, navit naveh5, jaclyn k anderson3 1division of clinical immunology and rheumatology, university of alabama at birmingham, birmingham, alabama, united states; 2vib infl ammati on research center, university of gent, gent, belgium; 3abbvie inc., north chicago, illinois, united states; 4abbvie, ljubljana, slovenia; 5abbvie, hod hasharon, israel conclusions � the rates of ibd aes in ada clinical trials were generally low across all indicati ons, with all events occurring in adult pati ents � axial spa pati ents are generally at higher risk of manifesti ng ibd – in the combined group of axspa pati ents (as and nr-axspa), the rates of ibd for ada-treated pati ents were numerically lower than for pbo-treated pati ents – in as pati ents, the rates of ibd for adaand pbo-treated pati ents were low (0.7/100 pys [95% ci, 0.4–1.1] and 0.0, respecti vely) and were similar to published pbo rates pooled across multi ple as clinical trials with tnf inhibitors (1.3/100 pys [95% ci, 0.2–4.8])1 � in pati ents at risk for ibd who require biologic therapy, ada is a reasonable therapeuti c opti on based on the observed low ibd event rates in ada clinical trials and its demonstrated effi cacy in treati ng uc and cd pati ents fri0444 results disclosures jr curti s has received research grants and/or consulti ng fees from amgen, bms, corrona, crescendo, janssen, pfi zer, and ucb. d elewaut has received research grants, consulti ng fees, and/or speaker’s fees from abbvie. s chen, m hojnik, n naveh, and jk anderson are employees of abbvie and may own stock/opti ons. references 1. braun, j. et al. arthriti s & rheum. 2007;57:639–47. acknowledgments abbvie funded the studies, contributed to their design, and parti cipated in data collecti on, analysis and interpretati on of the data, and in writi ng, review, and approval of the publicati on. medical writi ng support was provided by deepa venkitaramani, phd, of abbvie. assessment for inflammatory bowel disease ibd • the search criteria for ibd events included the following standardized meddra queries preferred terms and did not disti nguish between new onset ibd and fl are of pre-existi ng disease: – infl ammatory bowel disease (ibd) – ulcerati ve coliti s (uc) – crohn’s disease (cd) – ibd-not otherwise specifi ed (nos) – ulcerati ve procti ti s • in additi on to the meddra queries, manual assessment to disti nguish new-onset ibd and fl are of pre-existi ng disease was performed for events occurring in pati ents with axial spa (nr-axspa and as) statistical analyses • ibd events were defi ned as an ibd fl are in pati ents with pre-existi ng ibd, or new onset ibd among those without pre-existi ng ibd • incidence rates of ibd events (combined new onset and fl are) were calculated separately for placebo (pbo)and ada-treated pati ents during the pbo-controlled periods of interventi onal clinical trials of ada • overall incidence rates of ibd events were determined in pati ents treated with ada during the pbo-controlled periods and open-label extensions of all interventi onal clinical trials of ada • the risk of an ibd event over a 1-year period of ada treatment was also calculated – due to variable follow-up durati on in the studies included in this analysis the ti me period included was limited to 1 year to improve comparability between studies • incidence rates of ibd events are reported as events per 100 pati ent-years (pys) • 95% confi dence intervals (ci) were based on exact poisson confi dence limits • in spa, the overall rate of ibd was 0.5/100 pys, while the rates were 0, 0.8, 0.5, and 0.7/100 pys in psa, non-psa pspa, nr-axspa, and as, respecti vely (table 3) – 2216 pati ents with axspa (as: 2026, nr-axspa: 190) were exposed to ada; in as, 14 ibd events (7 new onset and 7 fl ares) were reported in 12 pati ents (7 new onset and 5 fl ares), while in nr-axspa, 2 ibd events were reported in 1 pati ent (2 fl ares) • there were no reports of ibd events in pediatric pati ents table 3. incidence of ibd events in pati ents from all non-registry ada clinical trials indication n (pys) all ibd aes, n ir/100 pys (95% ci) all ada trialsa 23 735 (36 404.6) 40 0.1 (0.1–0.2) all spab 3218 (3919.9) 19 0.5 (0.3–0.8) psa 837 (997.5) 0 0.0 non-psa pspa 165 (390.7) 3 0.8 (0.2–2.2) all axspac 2216 (2531.7) 16 0.6 (0.4–1.0) nr-axspa 190 (412.2) 2 0.5 (0.1–1.8) as 2026 (2119.5) 14 0.7 (0.4–1.1) rheumatoid arthritis 15 152 (24 813.0) 16 <0.1 (0.0–0.1) uveitis 387 (538.8) 1 0.2 (0.0–1.0) hidradenitis suppurativa 733 (836.3) 3 0.4 (0.1–1.1) adult psoriasis 3500 (5268.7) 1 <0.1 (0.0–0.1) pediatric psoriasis 111 (121.5) 0 0.0 all jiad 274 (797.4) 0 0.0 aall ada adult and pediatric pati ents during pbo-controlled periods and open-label extensions across all interventi onal studies excluding crohn’s disease, ulcerati ve coliti s, and intesti nal behcet’s disease. ball ada pati ents in all interventi onal studies of psa, non-psa pspa, nr-axspa, and as. call ada pati ents in all interventi onal studies of nr-axspa and as. dall ada pati ents in all interventi onal studies of jia, pjia, and peds era. ibd = infl ammatory bowel disease; ada = adalimumab; pys = pati ent years; aes = adverse events; ir = incidence rates; ci = confi dence interval; spa = spondyloarthriti s; psa = psoriati c arthriti s; pspa = non-psa peripheral spondyloarthriti s; axspa = axial spondyloarthriti s; nr-axspa = non-radiographic axspa; as = ankylosing spondyliti s; jia = juvenile idiopathic arthriti s; pjia = polyarti cular juvenile idiopathic arthriti s; peds era = pediatric enthesiti s-related arthriti s. • the risk of an ibd event occurring over a 1-year period in all interventi onal ada trials was 0.1/100 pys (table 4) • the 1-year risk of an ibd event was <0.1/100 pys in both ra and ps trials • the 1-year risk of an ibd event was 0.0 in psa, uveiti s, hs, pediatric ps, pjia, and peds era trials, since no ibd event was reported through 1 year of ada treatment table 4. risk of ibd event over 1-year in pati ents from all non-registry ada clinical trials indication n (pys) all ibd aes, n ir/100 pys (95% ci) all ada trialsa 23 735 (15 366.7) 15 0.1 (0.1–0.2) all spab 3218 (1711.4) 8 0.5 (0.2–0.9) psa 837 (491.6) 0 0.0 non-psa pspa 165 (154.1) 1 0.6 (0.0–3.6) all axspac 2216 (1065.7) 7 0.7 (0.3–1.4) nr-axspa 190 (166.0) 1 0.6 (0.0–3.4) as 2026 (899.6) 6 0.7 (0.2–1.5) rheumatoid arthritis 15 152 (10 072.3) 6 <0.1 (0.0–0.1) uveitis 387 (306.3) 0 0.0 hidradenitis suppurativa 733 (591.0) 0 0.0 adult psoriasis 3500 (2245.9) 1 <0.1 (0.0–0.2) pediatric psoriasis 111 (96.6) 0 0.0 all jiad 274 (234.4) 0 0.0 aall ada adult and pediatric pati ents in all interventi onal studies excluding crohn’s disease, ulcerati ve coliti s, and intesti nal behcet’s disease. ball ada pati ents in all interventi onal studies of psa, non-psa pspa, nr-axspa, and as. call ada pati ents in all interventi onal studies of nr-axspa and as. dall ada pati ents in all interventi onal studies of jia, pjia, and peds era. ibd = infl ammatory bowel disease; ada = adalimumab; pys = pati ent years; aes = adverse events; ir = incidence rates; ci = confi dence interval; spa = spondyloarthriti s; psa = psoriati c arthriti s; pspa = non-psa peripheral spondyloarthriti s; axspa = axial spondyloarthriti s; nr-axspa = non-radiographic axspa; as = ankylosing spondyliti s; jia = juvenile idiopathic arthriti s; pjia = polyarti cular juvenile idiopathic arthriti s; peds era = pediatric enthesiti s-related arthriti s. • ada was administered to 23 735 pati ents, representi ng 36 404.6 pys of exposure • incidence rates for ibd events during the pbo-controlled period of ada interventi onal trials were <0.1/100 pys for both ada and pbo-treated pati ents (table 2) • in axspa, the ibd rates in adaand pbo-treated pati ents during pbo-controlled period were 0.6/100 pys and 1.1/100 pys, respecti vely (table 2) – there was only 1 ibd event reported in a pati ent on ada treatment (in an as pati ent) and 1 ibd event reported in pati ents treated with pbo (in a nr-axspa pati ent) methods clinical trials • the rates of ibd aes in 73 phase 2–4 interventi onal ada clinical trials in rheumatoid arthriti s (ra), polyarti cular juvenile idiopathic arthriti s (pjia), pediatric enthesiti s-related arthriti s (peds era), uveiti s (non-infecti ous intermediate, posterior, or pan-uveiti s), hidradeniti s suppurati va (hs), adult and pediatric psoriasis (ps), psoriati c arthriti s (psa), non-psa peripheral spa (pspa), non-radiographic axial spondyloarthriti s (nr-axspa), and ankylosing spondyliti s (as) were analyzed (table 1) • trials in uc, cd, and intesti nal behcet’s disease (bd) were excluded from this analysis; however, pati ents with uc, cd, and bd were not excluded from the trials included in this analysis table 1. list of indicati ons and clinical trials indication no. of trials no. of patients all ada trialsa 73 23 735 psoriatic arthritis (psa) 4 837 non-psa peripheral spondyloarthritis (pspa) 1 165 non-radiographic axial spondyloarthritis (nr-axspa) 1 190 ankylosing spondylitis (as) 5 2026 rheumatoid arthritis 35 15 152 uveitis 2 387 hidradenitis suppurativa (hs) 4 733 adult psoriasis 16 3500 pediatric psoriasis 1 111 all juvenile idiopathic arthritisb 4 274 aall ada adult and pediatric pati ents in all interventi onal studies excluding crohn’s disease, ulcerati ve coliti s, and intesti nal behcet’s disease. ball ada pati ents in all interventi onal studies of pjia, and peds era. pjia = polyarti cular juvenile idiopathic arthriti s; peds era = pediatric enthesiti s-related arthriti s. fc17posterabbviecurtisincidenceofinflammatorybowel.pdf ¾ each study enrolled 18 healthy, white volunteers, aged 18 to 55. ¾ study 1: � baseline tewl was increased and skin hydration was decreased in dry-shaved sites. � following treatment with either dfd-01 or vehicle, tewl rates were lower in shaved sites compared with untreated sites and the difference was statistically significant at 1 hour (p<.001). � following treatment with both dfd-01 and vehicle, skin hydration levels increased to well within the normal range for intact non-shaved skin (table 1). ¾ study 2: � after subtracting changes in untreated control sites, both dfd-01 and vehicle increased r3 values, indicating greater skin elasticity. � the increase was significant for dfd-01 at 1 hour (p<.01). ¾ in study 1 there were no reports of serious or non-serious adverse events. ¾ in study 2 there was 1 non-serious adverse event of left-hand numbness that was judged to be unrelated to the study. dfd-01, a betamethasone dipropionate 0.05% spray lotion, reduces transepidermal water loss and improves skin hydration and elasticity j. mark jackson, md1; gary l grove, phd2; kent allenby, md3; tim houser, ms2 1university of louisville, louisville, ky; 2cyberderm clinical studies, broomall, pa; 3promius pharma, a subsidiary of dr. reddy’s laboratories, princeton, nj conclusions ¾ in these two studies both dfd-01 and its vehicle: 1) reduced transepidermal water loss and increased surface hydration of skin damaged by dry shaving and 2) transiently softened intact skin. ¾ these results support the moisturizing and emollient-like properties of dfd-01. methods table 1. results at 1, 2, & 4 hours after treatment study 1: skin hydration ¾ day 1 4 test sites were dry shaved (two 5 cm x 5 cm sites on the volar surface of each forearm). post-shaving evaporimeter measurements confirmed increased water loss from the test sites. ¾ day 2 – test sites were evaluated for 1) baseline transepidermal water loss (tewl) using an evaporimeter, and 2) capacitance (epidermal hydration) using a corneometer. � dfd-01 and vehicle (0.1 ml) were each applied to 1 test site on each arm, leaving 1 site on each arm as a damaged, untreated control. � tewl and capacitance measurements were repeated at 1, 2 and 4 hours after treatment. study 2: skin elasticity ¾ six 5 cm x 5 cm sites (3 sites on each volar forearm) were outlined and baseline cutometer measurements were taken from each site. dfd-01 and vehicle (0.1 ml) were randomly applied to 1 test site on each arm, with the center site on each arm serving as an untreated control. ¾ elasticity measurements were repeated at 1, 2, and 4 hours after treatment. three cutometer measures were taken from each site. the third measurement was used to control for measurement artefacts. treatment effects were determined by the change in control sites subtracted from change in treated sites. financial support: this study was funded and sponsored by the dr. reddy’s laboratories group of companies drl publication #785 results 0 2 4 6 8 10 12 14 16 18 20 pretreatment after 1 hour after 2 hours after 4 hours m ea n t e w l ra te ( gm /m 2/ ho ur ) time after treatment applied shaved but not treated dfd-01 vehicle not shaved, not treated 0 5 10 15 20 25 30 35 pretreatment after 1 hour after 2 hours after 4 hours m ea n ca pa ci ta nc e time after treatment shaved, but not treated dfd-01 vehicle not shaved, not treated introduction ¾ dfd-01 [sernivo™ (betamethasone dipropionate) spray, 0.05%] is approved for the treatment of mild to moderate plaque psoriasis in adults. ¾ in plaque psoriasis, the benefit of topical steroids is well established. in addition to the effects of the steroid, the vehicle formulation of topical steroids can also provide benefit. ¾ two studies were conducted to evaluate the effect of dfd-01 and its vehicle (vehicle) on skin hydration and elasticity in healthy volunteers. fc17posterpromiusjacksondfd01elasticity.pdf skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 357 in-depth review racial and ethnic disparities in malignant melanoma: a literature review mitchell taylor, ba1,2, robin farias-eisner, md, phd, mba1,2,3 1 school of medicine, creighton university, omaha, ne 2 chi health creighton university medical center – bergan mercy, omaha, ne 3 lynch comprehensive cancer research center, school of medicine, creighton university, omaha, ne melanoma is a tumor arising from uncontrolled proliferation of melanocytes, neural crest derived cells responsible for production of pigment in the basal layer of the epidermis.1 although melanoma only accounts for 5% of all skin tumors, it represents the most aggressive form of skin cancer and is responsible for 75% of deaths among skin cancer patients.2 over the past several decades, the incidence of melanoma has grown significantly worldwide, with a faster increase than any other cancer besides lung cancer in females.2,3 melanoma is the seventh most common malignancy in women and the fifth most common malignancy in men worldwide.3 in 2020 alone, 324,635 new cases of melanoma were reported worldwide accompanied by 57,043 deaths.4 melanoma is known for affecting younger and middleaged individuals, with an average age of diagnosis at 57.3 fair skin, prolonged exposure to ultraviolet radiation, and a family history of melanoma are all documented as major risk factors for developing melanoma. as with most other forms of cancer, survival rates are significantly improved with an early diagnosis, where patients diagnosed with abstract melanoma is a tumor arising from uncontrolled proliferation of melanocytes, neural crest derived cells responsible for production of pigment in the basal layer of the epidermis. while the prevalence of melanoma is greatest in fair-skinned populations, racial and ethnic minority populations disproportionately experience lower rates of survival when diagnosed with melanoma. recent studies indicate that, among minority populations, melanoma tends to present at a more advanced stage with more aggressive melanoma subtypes, increased and atypical distributions over the body, and increased tumor depths. populations of color are also thought to carry unique mutations in brca genes that may predispose them to developing melanoma and account for increased mortality rates. socioeconomic status has also been linked to melanoma disparities, where limited access to quality healthcare including skin exams, surgical treatment, health insurance, and education may result in decreased melanoma survival rates. the aim of this article is to review the relationship between melanoma and underserved communities as well as discuss the current explanations behind these observations. introduction skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 358 stage i melanoma have a 5-year survival rate of greater than 90%.3 melanoma presents with a greater variation in risk of incidence across different racial and ethnic groups compared to other forms of cancer.2,3,5,6 although the incidence of melanoma is greatest in fair-skinned populations, studies indicate that populations of color are reported to have lower survival rates when diagnosed with melanoma.7 it has been established that over the past decade, a disproportionate number of deaths due to cancer in the united states have occurred in populations of color, particularly in african americans. however, racial disparities with respect to melanoma have received little attention.8 potential explanations for these outcomes in minority populations include more advanced disease at presentation, more biologically aggressive tumor behavior, and socioeconomic status. due to these uncertainties, studies have attempted to elucidate the relationship between melanoma and racial and ethnic minority groups and the causes of increased mortality. it is imperative for physicians to understand the manifestations and outcomes of melanoma in these populations as to optimize prevention, early detection, and treatment options. therefore, the aim of this article is to review the relationship between melanoma and underserved communities as well as discuss the current explanations behind these observations. advanced stage of presentation compared to caucasians, ethnic minority populations are more likely to be diagnosed with an advanced stage of melanoma upon clinical presentation. studies by cormier et. al indicate that minority populations are approximately twice as likely to present with either stage ii or iii melanoma compared to caucasians.8 between groups, 10.2% of hispanics, 16.7% of african americans, 15.4% of american indians, and 9.6% of asian/pacific-islanders presented with stage iv melanoma while only 3.9% of caucasians had a similar diagnosis. african americans presented with the greatest degree of advanced melanoma, with a fourfold increase in stage iv melanoma diagnosis compared to caucasians. when melanoma is diagnosed at an early stage, treatment of the lesion via surgical resection is associated with favorable patient outcomes.7 however, once melanoma has advanced to a more aggressive stage, surgical resection is less effective, and the disease becomes increasingly difficult to manage. metastasis of melanoma has a poor long-term prognosis, where median survival with treatment ranges between 8 and 12 months. a comparison of melanoma depth between african americans and caucasians indicates that african americans on average present with deeper tumors.9 studies by mahendraraj et. al showed deeper melanoma lesions in african americans compared to caucasians across major melanoma subtypes, including superficial spreading (1.26 vs. 0.83mm), nodular melanoma (3.50 vs. 2.93mm), and lentigo maligna (1.07 vs. 0.63mm), respectively. overall, 8.1% of all african americans diagnosed with superficial spreading melanoma presented with tumors deeper than 3.00mm compared to only 3.1% of caucasians. additionally, racial and ethnic minority groups are also shown to have broader distributions of melanoma as well as lymph node involvement, conferring a more advanced staging and poorer prognosis. review skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 359 according to hu et. al, 26% of african americans and 18% of hispanics presented with regional or distant disease, compared to only 12% in caucasians.10 while caucasians most commonly present with melanoma on the trunk (34.5%), african americans frequently present with melanoma on the lower extremities and feet (56.1%).9,11 according to hsueh et. al, the prognosis for patients diagnosed with melanoma of the lower extremity is affected by the distance of the lesion from the trunk, where a more distal tumor carries a poorer prognosis.12 regarding lymph node invasion, 21.8% african americans diagnosed with nodular melanoma had lymph node positivity compared to only 17.8% of caucasians. collectively, adversative tumor characteristics burden minority populations with an advanced stage of melanoma diagnosis and overall decreased patient outcomes. melanoma subtype the presentation of melanoma among minority populations compared to caucasians differs considerably regarding melanoma subtype. studies show that the most common form of melanoma in african americans is acral lentiginous melanoma, accounting for 36% of all melanomas in this population.8,13 acral lentiginous melanoma also presents as a major subtype in other minority groups, accounting for 18% of melanomas in asian/pacific islanders and 9% in hispanic whites. in contrast, caucasians are most frequently diagnosed with the superficial spreading form of melanoma, while acral lentiginous melanoma only accounts for 1% of all caucasian melanoma diagnoses.9 acral lentiginous melanoma has a more aggressive behavior and poorer prognosis as compared to other melanoma subtypes.14 acral lentiginous melanoma presents atypically and is commonly found on the soles of the feet, palms, and nail beds.13 as a result, it is more difficult to detect and diagnose in populations of color, often going unnoticed or misdiagnosed as a wart, fungus, or dark nail.15 the presentation of these tumors reportedly delays diagnosis and treatment, leading to poorer patient outcomes and survival rates. acral lentiginous melanoma is associated with lower 5-year and 10-year survival rates compared to other melanoma subtypes; while all other cutaneous melanoma subtypes collectively have a 5-year and 10year survival rate of 91.3% and 87.5%, respectively, acral lentiginous melanoma has a 5-year and 10-year survival rate of 80.3% and 67.5%, respectively.9 acral lentiginous melanoma is consequently associated with a 12-fold increase in development of stage iv melanoma and a 2fold increase in mortality. molecular studies of brca1 and brca2 to better understand melanoma disparities in minority populations, studies have begun focusing on profiling genetic mutations involved with melanoma development. historically, studies with melanoma patients have directed attention to genetic mutations in braf, nras, and kit genes, which have long been associated with melanoma and are thought to be mutually excluding.16 more recently, research has focused on further characterizing the role of brca1/brca2 mutations in the development of melanoma. brca1 and brca2 belong to a class of tumor suppressing genes located on chromosomes 17 and 13, respectively.17 together, brca1 and brca2 respond to double-stranded dna breaks and play a critical role in dna repair mechanisms. cells lacking functional brca1/brca2 genes are unable to repair double-stranded dna skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 360 breaks, allowing these cells to accumulate genetic mutations and develop into cell clones with malignant potential. the status and clinical significance of these mutations in ethnic and racial minorities have been less researched and warrant further characterization. understanding the genetic mutations in these populations is essential for comprehensive healthcare management as well as detecting melanoma at earlier stages. while brca1 mutations have been overall less associated with melanoma development, individuals with brca2 mutations have demonstrated an increased risk of melanoma in several reports.18 in one study conducted by the national cancer institute, 3,728 individuals from breastovarian cancer families were evaluated, and individuals with a brca2 mutation were 2.5 times more likely to develop melanoma compared to those without the mutation.19 additional studies have established the presence of brca1/2 mutations in patients with a history of melanoma. in a study conducted by debinak et. al, 630 patients with a history of melanoma and 3,700 controls were genotyped for the prevalence of three common variants of brca2 mutations (t1915m, n991d, and n372h).20 this study found that the prevalence of the brca2-n991d variant was significantly greater in melanoma patients compared to the controls. however, association between the two other brca2 variants and melanoma was not proven to be statistically significant. further research is necessary in order to determine the contribution of brca2 mutations in melanoma development. across racial and ethnic groups, there are differences in the spectrum of brca1 and brca2 mutations that may account for observed melanoma disparities.21 in a study conducted by golan et. al with metastatic pancreatic cancer patients, a higher prevalence of germline brca mutations was observed in african americans compared to caucasians and patients of other races.22 african americans also demonstrated the highest degree of brca2 mutations (7.1%) compared to caucasians (4.4%), asians (4.1%), and other groups (1.6%). however, it is important to note that only 1.3% of the screened population in this study was african american, which may limit the ability to draw definitive conclusions. another study done by haffty et. al found that the relative distribution of brca1 and brca2 mutations differed between caucasian and african american breast cancer patients.23 they found that 80% of african american patients carried mutations in the brca2 gene while 69% of the fairskinned cohort harbored mutations in the brca1 gene. furthermore, 46% of the african american patients had variants of unknown significance compared to only 12% in the caucasian population. a third study conducted by gao et. al reported similar results with african american breast cancer patients demonstrating disproportionally greater frequencies of brca2 mutations.24 their study identified that, in african americans, four of five deleterious mutations and four of six missense mutations were involved on the brca2 gene. collectively, these results indicate significant differences in brca1/2 mutation frequencies that may be contributing to disparities in melanoma across populations. socioeconomic and demographic factors in addition to a more aggressive tumor biology and difficulty in diagnosing acral subtypes of melanoma, factors including socioeconomic status and access to healthcare have also been implicated in skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 361 lower melanoma survival rates in minority groups. populations of color diagnosed with melanoma are observed to have a lower socioeconomic status; a study by tripathi et. al demonstrated that, in a sample of patients diagnosed with cutaneous melanoma, african americans maintained a median household income of less than $38,000 compared to $63,000 or greater in nonhispanic whites.25 notably, a lower socioeconomic status has been associated with reduced 5-year survival in melanoma patients, where chang et. al reported a decreased survival rate in both early (83.2% vs. 90.9%) and late-stage (30.0% vs. 45.5%) melanoma patients with a low socioeconomic status compared with a higher economic status.26 a separate study conducted by linos et. al evaluated 29,792 melanoma cases in the state of california and found that the lowest socioeconomic status groups experienced the greatest incidence of thick melanomas greater than 4mm.27 access to health insurance has also been shown to vary by race and consequently affect clinical outcomes in melanoma patients.28 artiga et. al highlight that, during the year of 2019, 11% of african americans, 20% of hispanics, 22% of american indians and alaska natives (aian), and 13% of native hawaiians and other pacific islanders (nhopi) were uninsured compared to only 8% of caucasians. of those minority patients with insurance, 37% of african americans, 32% of hispanics, 38% of aian, and 30% of nhopi relied on medicaid coverage while 74% of caucasians were covered by private insurance. the type of insurance, specifically medicaid, has been associated with provider discrimination and is thought to contribute to melanoma-related disparities in underserved populations.29 medicaid patients on average experience lower acceptance rates for dermatology appointments, where only 32% of medicaid patients receive appointments while 85% of medicare and 87% of private insurance patients are accepted for appointments. medicaid patients also experience longer wait times for appointments; these patients wait an average of 50 days for an appointment while medicare and private insurance patients only wait 37 days before being seen by a dermatologist.30 with the observed barriers to accessing healthcare, minority patients are less likely to receive the medical interventions necessary to manage skin cancers and are consequently at higher risk of developing advanced-stage melanomas. thorough fullbody skin exams performed by medical professionals are standard and critical for early detection of skin cancers like melanoma. however, studies have indicated that minorities are less likely to have received full-body skin examinations as compared to the white population. according to the national health interview survey, individuals of hispanic and african american descent are less likely to have been screened for skin cancer compared to caucasians.31 their survey found that, in 2000, only 3.7% of hispanic persons and 6.2% of black individuals received a recent skin examination as compared to 8.9% of caucasians. for minority patients that receive skin checks and are diagnosed with melanoma, studies indicate that these patients experience an increased period between the diagnostic biopsy and surgical excision, known as the surgical interval.25 it is well documented that delay in treatment following biopsy is associated with increased melanoma-specific mortality rates, although surgical interval guidelines for melanoma are not well-defined.32 tripathi et. al found skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 362 that, when sociodemographic characteristics were controlled for, the average surgical interval for african american patients was 23.4 days while caucasian patients only waited 11.7 days between diagnosis and surgery.25 furthermore, african american patients had twice the odds of experiencing surgical intervals between 41 and 60 days, three times the odds of 61 to 90 days, and five times the odds of over 90 days from the time of diagnosis to treatment. the advanced stage of melanoma in minority populations is also thought to be due to lower skin cancer awareness in these groups. historically, darker-skinned individuals have perceived themselves to have a reduced or no risk for developing melanoma due to increased levels of protective pigment in their skin.33 this can also be attributed to the marketing of melanoma risks and preventions to target populations primarily consisting of blonde or red-haired and blue-eyed individuals.27 byrd et. al have commented on the matter, claiming that the lack of public education involving melanoma in populations of color may be a significant driver of advanced melanoma stages in these groups.34 in a study conducted by pipitone et. al, skin cancer awareness was compared between hispanic and non-hispanic caucasians.35 results indicated that awareness of melanoma skin cancer and risk perception among hispanic persons was significantly less compared to non-hispanic caucasians. furthermore, in another study conducted by buster et. al, african americans and hispanics were less likely to believe that skin cancer is affected by lifestyle choices, despite known impacts of ultraviolet radiation on skin cancer development.36 their study also revealed that these groups were more likely to believe that skin cancer is preceded by pain or other non-specific symptoms and that nothing can be done to protect against these tumors. overall, the lower socioeconomic status associated with a number of minority populations limits access to critical healthcare and educational recourses, ultimately contributing to the observed disparities and a reduced overall awareness. in conclusion, the number of reported melanoma cases has continued to rise in the past few decades. while the caucasian population accounts for the highest incidence of melanoma diagnoses, racial and ethnic minority populations disproportionately experience lower rates of survival when diagnosed with melanoma. among minority populations, melanoma tends to present at a more advanced stage with more aggressive melanoma subtypes, increased and atypical distributions over the body, and increased tumor depths. recent studies indicate that populations of color carry unique mutations in the brca genes that may predispose them to developing melanoma and account for increased mortality rates. socioeconomic status has also been linked to melanoma disparities, where limited access to quality healthcare including skin exams, insurance, and education may result in decreased melanoma survival rates. overall, it is imperative to incorporate melanoma disparities education into physician training in order to combat the systemic issues observed and improve the poor melanoma prognosis associated with populations of color. conflict of interest disclosures: none funding: none corresponding author: mitchell taylor, ba 3920 dewey ave conclusion skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 363 omaha, ne 68105 phone: 612-356-0360 email: mat96996@creighton.edu references: 1. domingues b, lopes jm, soares p, pópulo h. melanoma treatment in review. immunotargets and therapy. 2018; 7:35-49. 2. ward-peterson m, acuña jm, alkhalifah mk, et al. association between race/ethnicity and survival of melanoma patients in the united states over 3 decades: a secondary analysis of seer data. medicine (baltimore). 2016; 95:e3315. 3. heistein jb, acharya u. malignant melanoma. in: statpearls. treasure island (fl): statpearls publishing llc, 2021:. 4. sung h, ferlay j, siegel rl, et al. global cancer statistics 2020: globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries. ca: a cancer journal for clinicians. 2021; 71:209-249. 5. leonardi gc, falzone l, salemi r, et al. cutaneous melanoma: from pathogenesis to therapy. international journal of oncology. 2018; 52:1071-1080. 6. ferlay j, soerjomataram i, dikshit r, et al. cancer incidence and mortality worldwide: sources, methods and major patterns in globocan 2012. international journal of cancer. 2015; 136:e359-e386. 7. matthews nh, li wq, qureshi aa, weinstock ma, cho e. epidemiology of melanoma. in: ward wh, farma jm (eds). cutaneous melanoma: etiology and therapy. brisbane (au): 2017:. 8. cormier jn, xing y, ding m, et al. ethnic differences among patients with cutaneous melanoma. archives of internal medicine (1960). 2006; 166:1907-1914. 9. mahendraraj k, sidhu k, lau csm, mcroy gj, chamberlain rs, smith fo. malignant melanoma in african-americans: a populationbased clinical outcomes study involving 1106 african-american patients from the surveillance, epidemiology, and end result (seer) database (1988-2011). medicine (baltimore). 2017; 96:e6258. 10. hu s, parmet y, allen g, et al. disparity in melanoma: a trend analysis of melanoma incidence and stage at diagnosis among whites, hispanics, and blacks in florida. archives of dermatology (1960). 2009; 145:1369-1374. 11. erdei e, torres sm. a new understanding in the epidemiology of melanoma. expert review of anticancer therapy. 2010; 10:1811-1823. 12. hsueh ec, lucci a, qi k, morton dl. survival of patients with melanoma of the lower extremity decreases with distance from the trunk. cancer. 1999; 85:383-388. 13. tas f, erturk k. acral lentiginous melanoma is associated with certain poor prognostic histopathological factors but may not be correlated with nodal involvement, recurrence, and a worse survival. pathobiology (basel). 2018; 85:227-231. 14. alcarraz ce, morante z, mas l, et al. outcomes and prognostic factors for acral lentiginous melanoma in peruvian patients. journal of clinical oncology. 2016; 34:e21061. 15. gupta ak, bharadwaj m, mehrotra r. skin cancer concerns in people of color: risk factors and prevention. asian pacific journal of cancer prevention : apjcp. 2016; 17:5257-5264. 16. gutiérrez-castañeda ld, nova ja, tovar-parra jd. frequency of mutations in braf, nras, and kit in different populations and histological subtypes of melanoma: a systemic review. melanoma research. 2020; 30:62-70. 17. venkitaraman ar. cancer susceptibility and the functions of brca1 and brca2. cell. 2002; 108:171-182. 18. gumaste pv, penn la, cymerman rm, kirchhoff t, polsky d, mclellan b. skin cancer risk in brca1/2 mutation carriers. british journal of dermatology (1951). 2015; 172:1498-1506. 19. breast cancer linkage consortium, t. cancer risks in brca2 mutation carriers. jnci : journal of the national cancer institute. 1999; 91:13101316. 20. dębniak t, scott rj, górski b, et al. common variants of dna repair genes and malignant melanoma. european journal of cancer (1990). 2007; 44:110-114. 21. kurian aw. brca1 and brca2 mutations across race and ethnicity: distribution and clinical implications. current opinion in obstetrics & gynecology. 2010; 22:72-78. 22. golan t, kindler hl, park jo, et al. geographic and ethnic heterogeneity of germline brca1 or brca2 mutation prevalence among patients with metastatic pancreatic cancer screened for entry into the polo trial. journal of clinical oncology. 2020; 38:1442-1454. 23. haffty bg, silber a, matloff e, chung j, lannin d. racial differences in the incidence of brca1 and brca2 mutations in a cohort of early onset breast cancer patients: african american skin september 2022 volume 6 issue 5 (c) 2022 the authors. published by the national society for cutaneous medicine. 364 compared to white women. journal of medical genetics. 2006; 43:133-137. 24. qing g, tomlinson g, das s, cummings s. prevalence of brca1 and brca2 mutations among clinic-based african american families with breast cancer. 2000; . 25. tripathi r, archibald lk, mazmudar rs, et al. racial differences in time to treatment for melanoma. journal of the american academy of dermatology. 2020; 83:854-859. 26. chang ae, karnell lh, menck hr. the national cancer data base report on cutaneous and noncutaneous melanoma. cancer. 1998; 83:1664-1678. 27. linos e, swetter sm, cockburn mg, colditz ga, clarke ca. increasing burden of melanoma in the united states. journal of investigative dermatology. 2009; 129:1666-1674. 28. artiga s, hill l, orgera k, damico a. health coverage by race and ethnicity, 2010-2019 <https://www.kff.org/racial-equity-and-healthpolicy/issue-brief/health-coverage-by-race-andethnicity/>. accessed june 12,. 2021. 29. kooistra l, chiang k, dawes s, gittleman h, barnholtz-sloan j, bordeaux j. racial disparities and insurance status: an epidemiological analysis of ohio melanoma patients. journal of the american academy of dermatology. 2018; 78:998-1000. 30. resneck j, pletcher mj, lozano n. medicare, medicaid, and access to dermatologists: the effect of patient insurance on appointment access and wait times. journal of the american academy of dermatology. 2004; 50:85-92. 31. saraiya m, hall hi, thompson t, et al. skin cancer screening among u.s. adults from 1992, 1998, and 2000 national health interview surveys. preventive medicine. 2004; 39:308314. 32. huff ls, chang ca, thomas jf, et al. defining an acceptable period of time from melanoma biopsy to excision. dermatology reports. 2012; 4:e2. 33. goldenberg a, vujic i, sanlorenzo m, ortiz-urda s. melanoma risk perception and prevention behavior among african-americans: the minority melanoma paradox. clinical, cosmetic and investigational dermatology. 2015; 8:423-429. 34. byrd km, wilson dc, hoyler ss, peck gl. advanced presentation of melanoma in african americans. journal of the american academy of dermatology. 2004; 50:21-24. 35. pipitone m, robinson jk, camara c, chittineni b, fisher sg. skin cancer awareness in suburban employees: a hispanic perspective. journal of the american academy of dermatology. 2002; 47:118-123. 36. ezenwa e, buster k. health disparities and skin cancer in people of color. practical dermatology. 2019; :38-42. skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 612 brief article a rare case of cutaneous anaplastic large cell lymphoma in an adolescent female chelsea taylor schwartz, do1, samuel lassiter, oms2, david cleaver, do, faad, faocd3, nathan cleaver, do, faad, faocd4 1 still opti northeast regional medical center, kirksville, mo 2 lake erie college of osteopathic medicine, erie, pa 3 cleaver dermatology, kirksville, mo 4 cleaver medical dermatology, cumming, ga primary cutaneous anaplastic large cell lymphoma (pc-alcl) is the second most common group of cutaneous t-cell lymphoma's (ctcl), making up 25-30% of clinical cases.1 pc-alcl is a cd30 positive lymphoproliferative disorder that typically presents in 50 to 70-yearsold with a male predominance of 2:1. the typical presentation of pc-alcl is a solitary, or less commonly, a localized group, of nodules or papules that often ulcerate and persist for 34 weeks. extracutaneous dissemination is a rare complication, occurring in 10% of cases, with the most common site being regional abstract primary cutaneous anaplastic large cell lymphoma (c-alcl) is a cd30 positive lymphoproliferative disorder, which is the second most common group of cutaneous t-cell lymphomas. it is common in adults 50-70 years of age with a male to female ratio 2:1. here, we report a 14-year-old caucasian female who presented with a painless, growing, friable, hemorrhagic nodule on her right medial buccal cheek of 2 weeks’ duration. the lesion was traumatized during a basketball game and significant bleeding was noted. a shave biopsy was performed on the 1.7 cm x 1.3 cm lesion. histopathology demonstrated epidermal necrosis, acanthosis, large, atypical lymphocytes with a number mitoses, prominent eosinophils, and smaller lymphocytes. immunohistochemical staining revealed cd30 positivity of much of the tumor infiltrate but was not diffusely positive. rare cells were granzyme positive. alk-1, tdt, eber, cd1a were negative. the diagnosis was confirmed by a second dermatopathologist. the patient was referred to oncology. labs were within normal limits and pet/ct scan was negative for metastasis. the lesion started to spontaneously regress after the shave biopsy. spontaneous regression of c-alcl occurs in 20-42% of cases and usually has an indolent course, therefore, aggressive treatment is not appropriate. in most cases, solitary or localized lesions are treated with surgical excision or radiotherapy. although, about half of cases reoccur, but are not life threatening. this unusual case of calcl provides an additional example of a rare clinical presentation in an adolescent female and reiterates the important histopathological findings for diagnosis. introduction skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 613 lymph nodes.2 this however does not confer a worse prognosis. a 14-year-old caucasian female presented with a growing, painless, friable, 1.7 cm hemorrhagic nodule on the right buccal cheek for two weeks (figure 1). the patient stated the nodule was traumatized during a basketball game and experienced excessive bleeding. she was evaluated by urgent care and submental lymphadenopathy was noted on exam. the patient was prescribed oral antibiotics, but the lesion did not resolve. figure 1. a 1.7 cm x 1.3 cm painless, growing, friable, hemorrhagic nodule on the right buccal cheek a subsequent biopsy was performed. the histopathology demonstrated epidermal acanthosis with epidermotropism. in addition, overlying ulceration and necrosis was identified. there was an infiltrate extending to the dermal subcutaneous junction. the dermal infiltrate revealed large atypical lymphocytes with multiple irregular mitotic figures, pleomorphism, and prominent peripheral cytoplasm. immunohistochemistry revealed prominent cd30 expression within the infiltrate. cd3 and cd4 were positive. the tumor was negative for tdt, eber, cd1a, and alk-1. cd56 and granzyme showed minimal expression within smaller lymphocytes. the patient’s histologic differential diagnosis included cutaneous anaplastic large cell lymphoma and lymphomatoid papulosis. given the clinical presentation, the diagnosis of alcl was favored. the patient was referred to pediatric oncology for further evaluation. the initial biopsied lesion had spontaneously regressed along with the submental lymphadenopathy. a pet/ct did not show any evidence of metastatic disease. localized radiation and bone marrow biopsy was considered but no intervention was favored. primary cutaneous anaplastic large cell lymphoma is a cd-30 positive lymphoproliferative disorder. following mycosis fungoides, it is the second most common subtype of cutaneous t-cell lymphomas. many cases present in patients ages 50 to 70 years-old and are twice as likely to affect men than women. clinically, solitary or localized nodules, tumors, or papules are seen and usually present on the upper half of the body. the lesions are often ulcerated and present for 3-4 weeks’ duration. multifocal lesions present in 20% of patients and extracutaneous dissemination occurs in 10% of cases, usually to regional lymph nodes, but does not confer a poor prognosis. the lesions can spontaneously regress, but up to half reoccur. this case was unique in that the presentation was in a 14 yearold female with a display of early, local lymph node involvement, despite displaying a single lesion. histologically, this tumor typically displays cohesive sheets of large cells with a pleomorphic, anaplastic or immunoblastic case report discussion skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 614 cytomorphology.3 the cells typically have round, oval or irregularly shaped nuclei, a prominent eosinophilic nucleolus, and abundant cytoplasm. it should also be noted that up to 25% of cases display reedsternberg cells, further complicating the diagnosis. immunophenotype is cd4 positive with or without cd3 and negative for cd2 and cd5. to make a diagnosis of pc-alcl, cd30 must be expressed in most neoplastic cells. also, while cd30 positivity is often presented in the setting of lymphocytic malignancies, it can also be observed in a wide variety of benign conditions including common viral infections, scabies, and atopic dermatitis.8 differential diagnosis of pc-alcl includes lymphomatoid papulosis (lyp), systemic alcl, mycosis fungoides, and reactive lymphoid hyperplasia6. immunophenotype serves as a helpful tool for the differentiation of these neoplasms. pc-alcl can be differentiated from systemic alcl as the neoplastic cells in alcl do not express alk16. mycosis fungoides prototypically expresses cd3 and cd8, which can help distinguish this from pc-alcl as pc-alcl is cd8 negative. to differentiate pc-alcl from reactive lymphoid hyperplasia, a lymph node biopsy can be beneficial, with the visualization of dohle bodies and tangible body macrophages within local lymph nodes. the most difficult differentiation to make lies between lyp and pc-alc, as they have similar morphology and immunohistochemical profiles. clinical clues can help the differentiation between these two neoplasms as lyp tends to be a recurrent, self-healing condition with small (<1cm) papulonodular skin eruptions. lyp also rarely displays pustular lesions or ulcers. in comparison, pc-alcl tends to display larger skin lesions (>1cm) and ulceration is common. spontaneous regression does occur in pc-alcl, however, this is much less common and the majority of lesions do not regress. to further complicate this differential diagnosis, it is possible that there is overlap in these diagnoses as lyp can be concurrent to pc-alcl or precede this neoplasm3. in the situation where a differentiation isn’t possible, the tumors are denoted as "borderline".7 once a diagnosis has been established, it is important to avoid overtreatment as pcalcl follows an indolent course and local lymph node metastasis does not confer a worse prognosis. if the lesions are localized, the primary approach is surgical excision and radiation 6. in localized lesions where surgical excision is not possible, a low-dose oral methotrexate and local thermotherapy have been used with success.8 alternative treatment options in localized lesions of pcalcl include oral retinoids, with 13-cisretinoic acid found to be the most efficacious.8 if recurrence is observed multiple times or the nodules are multifocal and widespread, systemic therapy can be considered. in these cases, chop (cyclophosphamide, doxorubicin, vincristine and prednisone) has been used, however, it has not been shown to have improved outcome when compared to less aggressive treatments and recurrence is still seen.6 brentuximab vedotin, an anti-cd30 monoclonal antibody and anti-tubulin agent monomethyl auristatin, is fda approved for relapsing systemic alcl. it has been used in c-alcl and mf expressing cd30, but not enough information is available to determine if it is beneficial. conflict of interest disclosures: none funding: none corresponding author: chelsea taylor schwartz, do still opti northeast regional medical center email: chelseaschwartz@atsu.edu skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 615 references: 1. brown ra, fernandez-pol s, kim j. primary cutaneous anaplastic large cell lymphoma. j cutan pathol. 2017;44(6):570-577. doi:10.1111/cup.12937 2. ma l, katz y, sharan kp, schwarting r, kim as. epstein-barr virus positive anaplastic large cell lymphoma: myth or reality? int j clin exp pathol. 2010 nov;4(1):100–10. 3. dawn g, morrison a, morton r, bilsland d, jackson r. co-existent primary cutaneous anaplastic large cell lymphoma and lymphomatoid papulosis. clin exp dermatol. 2003 nov;28(6):620–4. 4. moodley n, nombona p, mosam a. primary cutaneous anaplastic large-cell lymphoma. dermatopathology (basel). 2019;6(2):163-169. published 2019 jun 26. doi:10.1159/000500259 5. borghi a, caselli e, di luca d, sebastiani a, perri p, seraceni s, et al. detection of chlamydophila pneumoniae and human herpesvirus 8 in primary cutaneous anaplastic large-cell lymphoma: a case report. infect agent cancer. 2013 oct;8(1):41. 6. perry e, karajgikar j, tabbara ia. primary cutaneous anaplastic large-cell lymphoma. am j clin oncol. 2013;36(5):526-529. doi:10.1097/coc.0b013e3182185aa2 7. david j. dicaudo, chapter 24 cutaneous t-cell lymphoma, nk-cell lymphoma, and myeloid leukemia, editor(s): dirk m. elston, tammie ferringer, christine j. ko, steven peckham, whitney a. high, david j. dicaudo, sunita bhuta, dermatopathology (second edition), w.b. saunders, 2014, pages 390-403, isbn 9780702055270 8. querfeld c, khan i, mahon b, et al. primary cutaneous and systemic anaplastic large cell lymphoma: clinicopathologic aspects and therapeutic options. oncology (williston park). 2010;24:574-587. skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 598 brief article a unique presentation and unusual cause of acute generalized exanthematous pustulosis: a case report gelan shamloul, bs1, emily mceldrew, do2, chelsea kesty, md2, richard mcclain, md2 1philadelphia college of osteopathic medicine, philadelphia, pa 2department of dermatology, lehigh valley health network, allentown, pa acute generalized exanthematous pustulosis (agep) is a severe, acute-onset cutaneous eruption of small, sterile pustules on an erythematous base, occurring with fever and a neutrophilic leukocytosis.1,2 agep primarily presents as an adverse drug reaction beginning 2-14 days following drug ingestion. the condition resolves spontaneously with desquamation within 1-2 weeks of drug discontinuation. here, we describe an unusual presentation of agep and discuss disease pathophysiology, histopathology, and current treatment guidelines. a 64-year-old male was admitted to the hospital for a painful rash that began three weeks after starting oral terbinafine for onychomycosis. the rash began on his neck and spread caudally to involve the trunk and extremities. the patient also had fevers, chills, and ulcer formation on his lower mucosal lip and tongue. ten days prior to presentation, he was evaluated at an outside hospital and discharged with a prednisone 60 mg taper for suspected erythema multiforme. a biopsy was not performed at this time. however, his rash continued to worsen after starting prednisone. on physical examination, he had diffuse, nearly confluent erythematous plaques with desquamation on the back, chest, and abdomen (figure 1). there were erythematous patches with dusky centers on the thighs, legs, arms, hands, and palms (figure 2). several small clusters of grouped pustules were present on the calves and thighs (figure 3). few erosions were noted in the lower mucosal lip and right tongue. nikolsky sign was negative, and there was no abstract acute generalized exanthematous pustulosis (agep) is a febrile, pustular eruption that has been reported in all ages. three weeks following oral terbinafine use, a 64-year-old male patient was admitted to the hospital for diffuse, nearly confluent erythematous plaques and desquamation, fevers, chills, and ulcer formation on his lower mucosal lip and tongue. ten days prior to presentation, he was evaluated and discharged with a prednisone 60 mg taper for suspected erythema multiforme. terbinafine was discontinued and the patient was monitored for systemic involvement. recognition of subtle pustules on a background of emlike lesions may facilitate the timely diagnosis and appropriate treatment of agep. introduction case report skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 599 ocular involvement or lymphadenopathy. pertinent positive laboratory findings included wbc 19.5 (4.5-10 thou/cmm), absolute neutrophils 16.8 (1.8-7.8 thou/cmm), absolute monocytes 1.4 (0.3-1.0 thou/cmm), and crp 93 (<7mg/l). comprehensive metabolic panel and sedimentation rate were within normal limits. a skin biopsy from the left thigh revealed spongiotic dermatitis with eosinophils. given clinical findings and the late timing of the skin biopsy, the diagnosis of agep was favored. figure 1. confluent erythematous plaques with desquamation on the torso. figure 2. erythematous patches with dusky centers on the right lower extremity. figure 3. small clusters of pustules on the thigh skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 600 acute generalized exanthematous pustulosis (agep) is a febrile, pustular eruption that has been reported in all ages. in the adult population, 90% of cases are a result of an adverse medication reaction, while viral infections are the most common cause in pediatric cases. antibiotics, particularly aminopenicillins, cephalosporins, quinolones, and sulfonamides are among the most cited offending agents.2 other medications have been implicated including calcium channel blockers, carbamazepine, antimalarials, fluconazole, and ibuprofen.3 rarely, reports have associated agep with terbinafine use, as in our patient’s presentation. onset of the drug eruption may appear anywhere between two days to two weeks following ingestion of the inciting agent. in our patient’s unique case, he had a delayed onset of this cutaneous eruption three weeks after terbinafine ingestion. following complete resolution of agep, patch testing can be used to determine the offending agent if it is unclear. infectious agents, including parvovirus b19, cytomegalovirus, chlamydia pneumoniae, mycoplasma pneumoniae, coxsackie b4, escherichia coli, and echinococcus have been implicated, especially in the pediatric population.2,4 rare cases have been reported with the bite of the brown recluse spider, mercury, and iopamidel, a radiocontrast media. 5,6 agep is characterized by acute onset of multiple, superficial, tiny (<5 mm) pustules on erythematous plaques classically beginning on the face and intertriginous areas and spreading cephalocaudally. the eruption may be associated with burning, pruritus, and facial edema. while unlikely, mucosal involvement has been reported and is generally limited to one mucosal region, often the lips or buccal mucosa.2,4 the rash resolves within several weeks with collaretteshaped or pinpoint foci of desquamation.2 manifestations of agep may mimic erythema multiforme (em), presenting with targetoid lesions, with or without mucosal involvement. in such presentations, pustules may be a late presenting sign of agep, as seen in our case. recognition of subtle pustules on a background of em-like lesions may facilitate the timely diagnosis of agep and alter the treatment course. agep is often druginduced whereas erythema multiforme is often caused by an infectious etiology, most commonly herpes simplex virus. in our patient’s case, a presumed diagnosis of erythema multiforme may have prompted empiric treatment with antiviral therapy, as well as allowed for possible re-initiation of terbinafine in the future, which could have caused relapse of his cutaneous eruption. additionally, em does not typically require specific laboratory monitoring whereas patients with agep must be monitored for liver and kidney dysfunction.7 other atypical presentations of agep may mimic the morbilliform rash of drug reaction with eosinophilia and systemic symptoms (dress) or the blisters and desquamation of toxic epidermal necrolysis (ten). the pathophysiology of agep involves a type-iv hypersensitivity reaction as demonstrated by in vitro and patch testing. in the early stage, drug-specific cd4 t-cells proliferate and migrate to the epidermis, inducing apoptosis of keratinocytes and leading to vesicle formation.4 release of interleukin (il)-8 results in neutrophilic chemotaxis, while secretion of interferongamma and macrophage colony stimulating factor (mcsf) aids in neutrophilic survivability.4 coupled together, this results discussion skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 601 in the transformation of vesicles into sterile pustules. recent research suggests an increased predisposition to agep in patients with il36rn gene mutations. the il36rn gene encodes for the anti-inflammatory interleukin, il-36ra, which functions to block the proinflammatory il-36.8 when mutated, there is uninhibited il-36 signaling and increased downstream production of il-8, thus facilitating pustule formation.8 histopathology can be diagnostic, demonstrating intraepidermal, intracorneal, and subcorneal pustules that mainly contain a neutrophilic, possibly eosinophilic, infiltrate.4 epidermal spongiosis and papillary dermal edema with a mixed infiltrate may also be present.2,4 treatment includes withdrawing the causative medication and monitoring for systemic involvement. the rash will selfresolve over the course of 1-2 weeks. topical steroids and antihistamines may be utilized to relieve associated pruritis. in severe cases, systemic prednisone or oral cyclosporine may be indicated, however there is no evidence that these therapies shorten disease duration.1,2 mortality from agep is rare (<5%) and occurs in patients with comorbidities presenting with mucosal involvement.4 conflict of interest disclosures: none funding: none corresponding author: gelan shamloul, bs lehigh valley health network department of dermatology 1259 south cedar crest blvd., suite 100 allentown, pa 18103 phone: (610) 437-4134 email: gs9402@pcom.edu references: 1. lee j, endicott a, shinkai k. acute generalized exanthematous pustulosis. jama dermatol. may 1 2021;157(5):589. doi:10.1001/jamadermatol.2020.5187 2. feldmeyer l, heidemeyer k, yawalkar n. acute generalized exanthematous pustulosis: pathogenesis, genetic background, clinical variants and therapy. int j mol sci. jul 27 2016;17(8)doi:10.3390/ijms17081214 3. roujeau jc, bioulac-sage p, bourseau c, et al. acute generalized exanthematous pustulosis. analysis of 63 cases. arch dermatol. sep 1991;127(9):1333-8. 4. szatkowski j, schwartz ra. acute generalized exanthematous pustulosis (agep): a review and update. j am acad dermatol. nov 2015;73(5):843-8. doi:10.1016/j.jaad.2015.07.017 5. davidovici bb, pavel d, cagnano e, rozenman d, halevy s. acute generalized exanthematous pustulosis following a spider bite: report of 3 cases. journal of the american academy of dermatology. 2006/09/01/ 2006;55(3):525-529. doi:https://doi.org/10.1016/j.jaad.2006.05.010 6. choi mj, kim hs, park hj, et al. clinicopathologic manifestations of 36 korean patients with acute generalized exanthematous pustulosis: a case series and review of the literature. ann dermatol. may 2010;22(2):163-9. doi:10.5021/ad.2010.22.2.163 7. hotz c, valeyrie-allanore l, haddad c, et al. systemic involvement of acute generalized exanthematous pustulosis: a retrospective study on 58 patients. br j dermatol. dec 2013;169(6):1223-32. doi:10.1111/bjd.12502 8. navarini aa, simpson ma, borradori l, yawalkar n, schlapbach c. homozygous missense mutation in il36rn in generalized pustular dermatosis with intraoral involvement compatible with both agep and generalized pustular psoriasis. jama dermatol. apr 2015;151(4):452-3. doi:10.1001/jamadermatol.2014.3848 https://doi.org/10.1016/j.jaad.2006.05.010 skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 821 brief article leukemia cutis as the presenting sign of acute myeloid leukemia in an hiv+ patient natalie garcia, bs1, charlotte mcrae, bs1, abigail smith, md2, lauren graham, md, phd2 1university of alabama at birmingham heersink school of medicine, birmingham, al 2university of alabama at birmingham, department of dermatology, birmingham, al leukemia cutis (lc) is a rare extramedullary cutaneous manifestation of leukemia that varies in terms of clinical presentation, type of leukemia, and timing of presentation in relation to systemic leukemia. rapidly developing bone marrow insufficiency causes leukemia and subsequent metastatic disease, which results in a wide array of cutaneous manifestations. lc presents with nonspecific skin findings which may mimic lesions found in other inflammatory, benign, or malignant conditions. lc typically presents during an active flare of leukemia or during relapse, but it rarely presents as the primary manifestation of systemic leukemia. a high index of suspicion is often necessary for diagnosis and driven by the clinician’s review of systems, physical exam, and evaluation of other co-morbid conditions. immunosuppressed patients, due to immunosuppressive medications taken to treat systemic auto-inflammatory diseases or conditions such as hiv/aids, are at higher risk for the development of secondary malignancies, particularly leukemia and lymphoma. hiv infection decreases the cd4 count and causes dysregulation of cd4 and cd8 activation. cd4 and cd8 cells play an important role in both cancer surveillance and the inactivation of oncogenic viruses. thus, abstract leukemia cutis (lc) is a rare extramedullary cutaneous manifestation of leukemia that varies in terms of clinical presentation, leukemia type, and timing of presentation in relation to systemic leukemia. lc typically presents following diagnosis of systemic leukemia and during an active flare or relapse. an estimated 3.7% of patients with acute myeloid leukemia (aml) develop lc. a 61-year-old male with poorly controlled hiv presented with a rash that began one month prior on his cheek as a red papule, which he believed was an ingrown hair. on exam, pink and yellow firm papules and nodules covered his entire body surface except the groin and axilla. one nodule held a peau d’orange appearance. the rash was overall asymptomatic, and he reported only increased fatigue. his cd4 count and viral load were 136 and 330,000 respectively. one punch biopsy revealed negative cultures for fungus, bacteria, and acid-fast bacilli. two biopsies sent for pathologic evaluation revealed aml of the skin. bone marrow biopsy confirmed aml. clinically the presentation of lc is nonspecific, and systemic symptoms rarely appear in conjunction with lc. high clinical suspicion and histopathologic examination are necessary for diagnosis of lc. introduction skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 822 even patients with adequate viral load suppression and a normal cd4 count also have an increased risk of malignancy.1 we present the case of an hiv positive male who developed diffuse dermal nodules, with subsequent biopsy revealing cutaneous leukemic metastases. a 61-year-old male with a past medical history of poorly controlled hiv presented to dermatology clinic with a new rash. the rash initially started one month prior to presentation on the patient’s cheek as a single red papule, which the patient believed to be an ingrown hair. the rash then spread to cover all surfaces of his body except his groin and axilla. on exam, pink and yellow firm papules and nodules covered nearly his entire body surface (figure 1 and 2). the first nodule to appear on the patient’s trunk was on the left shoulder and held a peau d’orange appearance. the patient reported that the rash was overall asymptomatic, as he was not in pain, did not itch, and had not experienced drainage or oozing from any of the nodules. the patient also denied systemic symptoms of chills, fever, weight loss, night sweats, and swollen lymph nodes; however, he experienced fatigue following the onset of the rash. figure 1. leukemia cutis. (left) the nodules over the extremities have a more violaceous appearance. (right) the first nodule to appear on the patient’s trunk was on the posterior left shoulder and held a peau d’orange appearance. at the time of presentation, the patient’s last charted cd4 count and viral load were 136 and 330,000 respectively. review of clinic notes suggested the patient had been instructed to discontinue his anti-retroviral therapy (art) pending evaluation of his rash. due to subsequent lack of improvement of his rash, he was restarted on art. the differential diagnosis based on clinical history and presentation included reticulohistiocytosis, mastocytosis, erythema elevatum diutinum, other granulomatous disorders, b-cell lymphoma, and atypical infectious etiologies given his low cd4 count. one punch biopsy sent for tissue culture was negative for fungus, bacteria, and acid-fast bacilli. two punch biopsies sent for pathologic evaluation revealed acute myeloid leukemia (aml) of the skin, resulting in the diagnosis of leukemia cutis (lc). subsequent bone marrow aspirate was obtained, and gross examination revealed hypercellular marrow with no overt dysplasia or increase in blasts. cytogenetic testing revealed an abnormal aml fluorescence in case report figure 2. leukemia cutis. there are numerous pink to salmon-colored firm papules and nodules on the trunk. skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 823 situ hybridization (fish) panel, which demonstrated that 3.6% of the cells had a rearrangement involving the kmt2a gene at 11q23. clinically the appearance of lc is nonspecific, ranging from solitary to multiple papules, nodules, blistering ulcers, or diffuse rash classically of the extremities.2 abnormal cutaneous findings in this patient led to cytogenetic bone marrow aspirate analysis, which revealed a rearrangement in the kmt2a gene responsible for the regulation of hematopoiesis and gene expression.3 this patient was ultimately diagnosed with acute myeloid leukemia (aml), and only 2.9-3.7% of patients with aml are estimated to develop lc.2 of the patients with aml who develop lc, only 7% of those patients present without systemic evidence of leukemia. thus approximately 0.2% of patients with aml will present with lc in the absence of abnormal complete blood count, bone marrow aspirate, or peripheral blood smear.2 classic symptoms of leukemia, such as thrombocytopenia, anemia, and fever, rarely appear in conjunction with lc, as was the case with our patient.4 the presentation of lc does not follow a clear pattern, and clinical observation alone cannot ensure definitive diagnosis. a thorough history, high clinical suspicion, histopathologic examination, blood work, and bone marrow analysis are important for the diagnosis of lc due to its range of presentations, classifications, and timing. the diagnosis of leukemia cutis is important to consider, regardless of cd4 count or presence of systemic leukemia, in immunosuppressed patients. conflict of interest disclosures: none funding: none corresponding author: natalie garcia, bs university of alabama at birmingham heersink school of medicine email: nhvoss@uab.edu references: 1. wilkins k, turner r, dolev jc, leboit pe, berger tg, maurer ta. cutaneous malignancy and human immunodeficiency virus disease. j am acad dermatol. 2006;54(2):189-210. doi:10.1016/j.jaad.2004.11.060 2. rao ag, danturty i. leukemia cutis. indian j dermatol. 2012;57(6):504. doi:10.4103/00195154.103086 3. el chaer f, keng m, ballen kk. mll-rearranged acute lymphoblastic leukemia. curr hematol malig rep. 2020;15(2):83-89. doi:10.1007/s11899-020-00582-5 4. findakly d, amar s. a rare case of leukemia cutis as the first presentation of a myelodysplastic syndrome to acute myeloid leukemia transformation. cureus. 2020;12(6):e8698. published 2020 jun 19. doi:10.7759/cureus.8698 discussion conclusion powerpoint presentation a clinical impact study of dermatologists’ use of the 23or 35-gene expression profile (gep) tests to guide surgical excision and enhance management plan confidence aaron s farberg, md1, kelli l ahmed, phd2, briana b rackley, phd2, jennifer j siegel, phd2, brooke h russell, phd2, jason h rogers, msc2, sarah j kurley, phd2, and matthew s goldberg, md2,3 1baylor scott & white health system, dallas, tx 2castle biosciences, inc., friendswood, tx 3icahn school of medicine at mount sinai, new york, ny › the 23-gene expression profile (gep) and 35-gep tests are clinically available, objective ancillary diagnostic tools that facilitate diagnosis of melanocytic lesions with ambiguous histopathology. the tests use proprietary algorithms to provide results: suggestive of benign neoplasm; intermediate (cannot rule out malignancy); or suggestive of malignant neoplasm with high accuracy.1-6 › communication between the diagnosing dermatopathologist/pathologist and the treating clinician is key to establishing appropriate patient management.7,8 there are circumstances when a dermatologist may find additional diagnostic information helpful in determining excision and follow-up actions.9,10 background methods clinical impact the majority of excision decisions and follow-up changes were aligned with gep results across the uncertain scenarios. there was also an increase in management plan confidence with gep results provided ›. › clinicians were invited for study participation based on prior use of diagnostic gep testing (minimum 3 encounters with gep results). thirty-two board certified dermatologists participated in this institutional review board (irb)-approved study. clinicians were asked three questions per scenario: 1) how would you treat the patient? no further treatment necessary, no further treatment necessary if lesion appears completely excised, excise <5 mm margins (narrow but complete), excise ≥5 mm margins (but <1 cm), wide local excision (excise ≥1 cm; 2) which follow-up schedule would you recommend? every 12, 6, 3, or every month; 3) how confident are you in this management plan? 1 (not confident), 2 (slightly confident), 3 (somewhat confident), 4 (fairly confident), 5 (completely confident). › clinical and diagnostic information for six uncertain patient scenarios was provided (table 1). diagnostic information was taken from real-world pathology reports of melanocytic lesions and displayed in mock form including the diagnosis and microscopic description. clinical information was based on common clinical situations that may alter patient treatment. gep test results were either not provided (baseline), benign, or malignant for each patient scenario. acknowledgments & disclosures asf has served as a consultant for castle biosciences, inc. kla, bbr, jjs, bhr, jhr, sjk, and msg are employee shareholders of castle biosciences, inc. the study was supported by castle biosciences, inc. presented at the winter clinical dermatology conference hawaii® (wch23), january 13-18, 2023, kohala coast, hawaii (encore presentation in part from asds 2022) for more information: afarberg@castlebiosciences.com results references ›gep results can aid dermatologists in decision making to achieve appropriate management plans ›management changes, including surgical excisions and follow-up frequency, were aligned with gep results for these uncertain clinical scenarios ›scenario-specific survey results demonstrate that a personalized approach can be achieved with gep conclusions results 1. clarke, l. e. et al. j cutan pathol 2015. 42 (4) 244–252. 2. clarke, l. e. et al. cancer 2017. 123 (4) 617–628. 3. clarke, l. e. et al. personalized medicine 2020. 17 (5) 361–371. 4. estrada, s. et al. skin 2020. 4 (6) 506–522. 5. ko, j. s. et al. cancer epidem biomar prev 2017. 26 (7) 1107–1113. 6. ko, j. s. et al. human pathology 2019. 86 213–221. 7. smith, shane d. b., et. al. jama dermatol. 2021. 157(9):1033-1034. 8. cockerell, c. dermatol surg. 2018. 44(2):175-176. 9. cockerell c, et al. personalized medicine. 2017. 14(2):123-130. 10. farberg, a. et al. skin 2020. 4 (6) 523–533. scan or click here for more info here we present dermatologist management plans and confidence utilizing diagnostic gep results in uncertain clinical and diagnostic scenarios ›. excision follow-up confidence gep result a v e ra g e % c h a n g e benign benign malignantmalignant benign malignant -50 50 0 100 d e c re a se in c re a se baseline figure 1. overall clinical impact across all ambiguous scenarios figure 2. gep results impact surgical excision planning and margin decisions figure 3. gep results alter recommended follow-up frequency › clinical impact was assessed by calculating the mean percent of no change, increase in change, or decrease in change relative to no gep results (baseline) for each scenario and normalized to 100%. › surgical margins: when a malignant gep result wass provided, there was an increase in surgical treatment for most scenarios. when a benign gep result was received, there was a decrease in surgical management intensity in most scenarios. table 1. ambiguous lesion scenarios from real-world pathology reports clinical impression diagnosis included excision recommendation cosmetic site melanocytic neoplasm, atypical melanocytic proliferation no cosmetic site dysplastic nevus with features of regression yes personal history of melanoma melanocytic neoplasm, atypical melanocytic proliferation no personal history of melanoma melanocytic neoplasm, deep penetrating yes comorbidities atypical intraepidermal melanocytic proliferation (aimp) yes high clinical suspicion atypical intraepidermal melanocytic proliferation (aimp) yes malignant gep baseline (no gep) benign gep malignant gep baseline (no gep)benign gep mailto:afarberg@castlebiosciences.com https://castletestinfo.com/mypath-melanoma-diffdx-melanoma/scientific-references/ https://castletestinfo.com/mypath-melanoma-diffdx-melanoma/scientific-references/ dd_01_036 winter clinical hawaii 2023 poster survey v2 slide 1 skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 837 brief article a violaceous mass of the chest: an unsuspected diagnosis of primary ewing sarcoma adam levin, do1, armaan guraya, do2, leela athalye, do3 1department of dermatology, prime west consortium, newport beach, ca 2department of internal medicine, howard university hospital, washington, d.c. 3island dermatology, newport beach, ca a 30-year-old female with no past medical history presented to our dermatology clinic approximately three weeks after she noticed a rapidly growing asymptomatic plaque on her chest. on exam the patient was noted to have an indurated round non-mobile subcutaneous plaque with a light blue to violaceous color which measured 4.2 x 4 cm. no lymphadenopathy was found, and the exam was otherwise normal. the patient was biopsied the day of presentation and was prescribed doxycycline daily for 1 week. pathologic examination of the biopsy specimen identified a high grade malignant small round blue cell tumor. immunohistochemistry was performed and the tumor cells were found to be fli-1, nkx2.2, cd99, ki-67 and vimentin positive. molecular studies were also performed and were positive for ewsr1 gene rearrangement. the diagnosis of primary cutaneous ewing sarcoma was confirmed, and the patient was referred to oncology and general surgery. on follow up approximately one month after initial presentation, the tumor was re-examined and was found to have grown to 4.5 x 4.1 cm. the patient has since been started on chemotherapy with plans to have the tumor resected after her first round of chemotherapy is complete. epidemiology with a peak incidence between 10 to 15 years of age, ewing sarcoma (es) is the second most common primary bone cancer. almost a third of cases occur in children under 10, but the incidence in the elderly is unknown. the disease disproportionately affects males and has a predilection for abstract ewing sarcoma is the second most common primary bone cancer. to date, only a few cases of primary cutaneous ewing sarcoma have been published. we present a unique case of primary cutaneous ewing sarcoma, which presented as a blue to violaceous mass on a young woman’s chest. the lesion clinically did not align with previous reports of primary cutaneous ewing sarcoma but pathology and immunohistochemical stains confirmed the diagnosis. because primary cutaneous ewing sarcoma may masquerade as benign tumors, dermatologists must be suspicious of otherwise benign looking tumors. case report discussion skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 838 caucasian patients.1 on the other hand, primary cutaneous es occurs more often in females and at later ages. it also tends to have a more favorable prognosis.2 figure 1. indurated, non-mobile, violaceous plaque on the chest. presentation primary cutaneous ewing sarcoma is only described in few case reports and series. its clinical appearance can vary widely, making diagnosis difficult and necessitating biopsy, cytology, and immunohistochemistry. the primary lesion is composed of a mass in the dermis but is generally described as having pink or brown nodules with keratotic surfaces.2 our case presented with a mass in the dermis but with a blue to violaceous color being most apparent on the skin surface as can be seen in image 1. histopathology & immunohistochemistry histopathologic evaluation of es reveals small round cells with abundant cytoplasm and small nuclei. this characteristic is part of the family of tumors of childhood consisting of small blue round cell tumors. periodicacid-schiff staining can also be useful to detect this cytoplasm due to its glycogen content. cd99 is an immunohistochemical biomarker highly sensitive for es, but with low specificity. there are a host of other markers that may aid in identification (i.e. s100, synaptophysin, cd45, vimentin, etc.), but their low specificity necessitates fluorescence in situ hybridization (fish) or reverse transcription-polymerase chain reaction for diagnosis.3 t(11;22)(q24;q12) is the most common gene rearrangement. ews-fli1 is a hybrid gene created in over 80% of cases of es by the combination of the ews and fli1 genes on 22q12 and 11q24, respectively.4 prognosis and treatment treatment, regardless of the presence of metastasis, includes systemic chemotherapy and surgery or radiotherapy. the euro ewing 2008 treatment protocol has been used in cutaneous es patients who can be appropriately treated with neoadjuvant chemotherapy. it consists of induction with 6 cycles of vincristine, ifosfamide, doxorubicin and etoposide (vide), followed by the appropriate prophylaxis.6 because smaller tumors may be seen more easily on the skin as compared to bone, primary cutaneous es may be caught sooner. this potential for earlier detection has led to the idea of treatment regimens with less toxic medications, however clinical trials are still needed to confirm. even given the earlier detection, roughly a tenth of these tumors already have metastasized by the time of presentation. for now, cutaneous es is treated as aggressively as es of the bone. nonetheless, survival is far superior in cutaneous es, with a 91% survival at 10 years.7, the risk of metastasis if undetected and consequently poorer prognosis makes early diagnosis and suspicion of a newly acquired lesion important for the clinician. conflict of interest disclosures: none funding: none skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 839 corresponding author: adam levin, do department of dermatology prime west consortium, newport beach, ca email: aglevin2@gmail.com references: 1. esiashvili n, goodman m, marcus rb. changes in incidence and survival of ewing sarcoma patients over the past 3 decades. journal of pediatric hematology/oncology. 2008;30(6):425430. doi:10.1097/mph.0b013e31816e22f3 2. oliveira filho, jayme de, et al. “primary cutaneous ewing sarcoma--case report.” anais brasileiros de dermatologia, sociedade brasileira de dermatologia, 2014, https://www.ncbi.nlm.nih.gov/pmc/articles/pmc40 56713/. 3. riggi n, stamenkovic i. the biology of ewing sarcoma. cancer letters. 2007;254(1):1-10. doi:10.1016/j.canlet.2006.12.009 4. lessnick sl, ladanyi m. molecular pathogenesis of ewing sarcoma: new therapeutic and transcriptional targets. annual review of pathology: mechanisms of disease. 2012;7(1):145-159. doi:10.1146/annurev-pathol011110-130237 5. durer s, shaikh h. cancer, ewing sarcoma. pubmed. published 2020. https://www.ncbi.nlm.nih.gov/books/nbk559183/ 6. “study in localized and disseminated ewing sarcoma full text view.” study in localized and disseminated ewing sarcoma full text view clinicaltrials.gov, https://clinicaltrials.gov/ct2/show/nct00987636. 7. delaplace m, lhommet c, de pinieux g, vergier b, de muret a, machet l. primary cutaneous ewing sarcoma: a systematic review focused on treatment and outcome. british journal of dermatology. 2012;166(4):721-726. doi:10.1111/j.1365-2133.2011.10743.x https://www.ncbi.nlm.nih.gov/books/nbk559183/ microsoft word wbc.doc skin in-depth reviews cutaneous implications of whole body cryotherapy aaron s. farberg, mda, stephen donohue, bs, atcb, alexander m. farbergc, ms, rebeca w. teplitzd, ba, darrell s. rigel, md, mse adepartment of dermatology, icahn school of medicine at mount sinai, new york, ny bhead athletic trainer, new york yankees, new york, ny cdepartment of chemistry, brandeis university, waltham ma dmedical student, new york institute of technology college of osteopathic medicine, old westbury, ny eclinical professor, department of dermatology, nyu school of medicine, new york, ny the science of aging has proceeded in numerous directions. an equally vast number of therapies have been suggested and/or used to prevent or reverse the aging process. whole body cryotherapy (wbc) is a medical treatment utilizing sub-freezing temperatures to enhance recovery after exercise and facilitate injury rehabilitation.1,2 it is considerably more convenient, but also more expensive than traditional forms of recovery cryotherapy (i.e. cold ice water immersion). although originally developed in 1978 by toshima yamauchi in japan to treat chronic medical conditions such as rheumatoid arthritis, wbc is increasingly employed for a variety of purposes.3 popularized by star athletes such as lebron james and kobe bryant, many major sports teams have purchased cryo-chambers to potentially enhance post-athletic muscle recovery. endorsements from celebrities including jennifer aniston and jessica alba have brought this treatment into public light for its use in the cosmetic industry.4 recently, wbc has been advocated to help skin appear and feel healthier, fight age-related deficiencies, and increase antioxidant production. the purpose of this paper is to review the current literature regarding the claims of potential benefits and possible risks of wbc related to the skin. wbc involves single or repeated exposure to extremely cold dry air (usually between -100°c and -150°c) in a specialized chamber or room july 2017 volume i issue i copyright 2017 the national society for cutaneous medicine 15 whole body cryotherapy (wbc) is a medical treatment utilizing sub-freezing temperatures to enhance recovery after exercise and facilitate injury rehabilitation. recently the therapy has been advocated to help skin appear and feel healthier, fight age-related deficiencies, and increase antioxidant production. the currently available evidence appears to be insufficient to support the use of wbc for improving skin and there is some small potential for risk. there are no well-controlled studies evaluating the clinical effects of wbc on the skin. although there is selected data to support possible theories for wbc’s purported skin rejuvenation effects, the evidence at this time remains limited. further investigation may be warranted to determine if wbc can actually have a proven beneficial effect on skin. abstract review skin july 2017 volume i issue i 16 copyright 2017 the national society for cutaneous medicine for a short period of time (2-5 minutes per exposure). during these exposures, individuals wear minimal clothing, gloves, and socks to reduce the risk of cold-related injury. regimens include up to daily treatment sessions and are recommended to continue indefinitely for prolonged and optimal results. the principle of cryotherapy is to extract heat from body tissue to attain its various clinical effects. in the field of dermatology, cryotherapy has been used to provide exfoliation for treatment of actinic keratoses and photodamaged skin by a cryo-peeling technique.5 wbc does not reach the similar tissue temperatures and remains non-ablative. therefore one would expect to achieve only a mild clinical improvement for related skin disorders. histological studies have revealed that such ablative therapies may improve collagen synthesis and skin elasticity.6,7 studies have shown the ability of wbc to reduce skin and intramuscular temperature.8-10 however, temperature reductions were small with almost no effect on core temperature. other forms of cooling including cold water immersion and ice packs offered similar minimal reductions. cryolipolysis used for fat reduction has been reported to improve skin elasticity following treatment.11 assuming this hypothesis to be correct, wbc may possibly stimulate collagen and hyaluronic acid production thereby improving skin elasticity, firmness, and promote a smoother complexion. other claims for wbc have included improvement for cellulite and psoriasis. additional claims include reducing pore size and blemishes as well as alleviating sun damage. however, all these noted claims for clinical benefits of wbc are based upon anecdotal experiences or product websites.12-14 overall, users of wbc have been led to expect a more youthful appearance, but there have been no controlled studies to date demonstrating these results. to date, there appears to be no evidence supporting the cosmetic claims of wbc or if it definitively offers any additional cutaneous clinical effect. rapid cooling of the skin results in strong vasoconstriction of the skin capillaries. this is associated with enhanced venous return of cooled blood which results in activation of arterial baroreceptors and increase in parasympathetic stimulation of the heart.15 this in turn causes an increased perfusion of the skin upon warming. further studies have revealed improved circulation including a significant increase in cutaneous microcirculation following wbc for up to 10 days.16 additional studies are needed to determine the clinical significance of the possibly enhanced cutaneous blood flow on skin related processes. evidence regarding wbc’s effect on oxidative stress is conflicting and limited. several studies have yielded either an increase or decrease in antioxidant status.17-19 each study had significant limitations that contributed to the equivocal findings. further research would need to include specific cell-signaling events and biomarkers to better determine any true clinical dermatologic impact. there is limited reported evidence of adverse cutaneous effects with the use of wbc.1,12 however, most studies did not actively investigate predefined adverse events. caution should be taken given the hazards that extreme temperature may present. isolated complications such as blistering and frostbite have been anecdotally reported and attributed to oversight during treatment. however, if proper protocol is followed and relevant contraindications are adhered to, it appears relatively unlikely for a patient to experience any significant harm. in summary, the currently available evidence appears to be insufficient to support the use of wbc for improving medical or appearance related skin issues and there is some small potential for risk. there are no well-controlled studies evaluating the clinical effects of wbc skin july 2017 volume i issue i 17 copyright 2017 the national society for cutaneous medicine on the skin. although there is selected data to support possible theories for wbc’s purported skin rejuvenation effects, the evidence at this time is very limited. further investigation may be warranted to determine if wbc could actually have a proven beneficial effect on skin. conflict of interest disclosures: none. funding: none. corresponding author: aaron s. farberg, md department of dermatology icahn school of medicine at mount sinai 35 e 35th st. #208 new york, new york 10016 email: aaron.farberg@gmail.com phone: 847-721-2725 references: 1) costello jt, baker pra, minett gm, bieuzen f, steward ib, bleakley c. whole-body cryotherapy (extreme cold air exposure) for preventing and treating muscle soreness after exercise in adults. cochrane database syst rev. 2015;9:cd010789. 2) banfi g, lombardi g, colombini a, melegati g. whole-body cryotherapy in athletes. sports med. 2010;40;509-517. 3) hirvonen he, mikkelsson mk, kautiainen h, pohjolainen th, leirisalo-repo m. effectiveness of different cryotherapies on pain and disease activity in active rheumatoid arthritis. a randomized single blinded controlled trial. clin exp rheumatol. 2006;24;295-301. 4) mickle k. cryotherapy promises to burn 800 calories in 3 minutes. shape magazine. feb 17, 2015. 5) deonizio j, werner b, mulinari-brenner fa. histological comparison of two cryopeeling methods for photodamaged skin. isrn dermatol. 2014:950754. 6) chiarello se. cryopeeling (extensive cryosurgery) for treatment of actinic keratoses: an update and comparison. dermatolog surg. 2000;26:728–732. 7) roy d. ablative facial resurfacing. dermatol clin. 2005;23(3):549-59. 8) bleakley cm, bieuzen f, davison gw, costello jt. whole-body cryotherapy: empirical evidence and theoretical perspectives. sports med. 2014;5:25-36 9) costello jt, culligan k, selfe j, donnelly ae. muscle, skin and core temperature after -110°c cold air and 8°c water treatment. plos one. 2012;7(11):e48190. 10) costello j, mcinerney cd, bleakley cm, selfe j, donnelly a. the use of thermal imaging in assessing skin temperature following cryotherapy: a review. j therm biol. 2012;37:103–110. 11) carruthers j, stevens wg, carruthers a, humphrey s. cryolipolysis and skin tightening. dermatol surg. 2014;40suppl12:s184-9. 12) cryo: beauty & anti-aging. available: url:http://cryo.com/benefits-usa/beauty-usa/. accessed: 5/31/2016 13) texas cryotherapy: cryotherapy benefits. available: url:http://www.ihpcryotherapy.com/benefits.html. accessed: 5/31/2016 14) albert-beitch c. you’ve heard of brain freeze--how about a whole body freeze? inc magazine. dec 4, 2014. 15) pump b, shiraishi m, gabrielsen a, bie p, christensen nj, norsk p. cardiovascular effects of static carotid baroreceptor stimulation during water immersion in humans. am j physiol heart circul physiol. 2001;280:h2607–h2615. 16) szygula r, dybek t, klimek a, tubek s. impact of 10 sessions of whole body cryostimulation on cutaneous microcirculation measured by laser doppler flowmetry. j human kinetics. 2011;30:75-83. 17) miller e, markiewicz l, saluk j, majsterek i. effect of short-term cryostimulation on antioxidative status and its clinical applications in humans. eur j appl physiol. 2012;112:1645–1652. 18) bleakley cm, davison gw. what is the biochemical and physiological rationale for using cold-water immersion in sports recovery? a systematic review. br j sports med. 2010;44:179–187. 19) mila-kierzenkowska c, woz´niak a, woz´niak b, et al. whole body cryostimulation in kayaker women: a study of the effect of cryogenic temperatures on oxidative stress after the exercise. j sports med phys fitness. 2009;49:201–207. skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 732 short communication acneiform eruption of monkeypox in a pilot faraz yousefian, do1, christopher kowalczyk, do2, nevada norris, pa-c2, carlos ricotti, md, faad2, francisco a. kerdel, md, faad2 1 center for clinical and cosmetic research, aventura, fl 2 larkin community hospital department of dermatology, miami, fl monkeypox outbreaks have been on the rise since may 2022, and 22,630 cases have been reported as of september 2022 in the united states.1,2 human-to-human close contact and exposure to respiratory droplets have caused a rapid increase in cases, the majority stemming from men having sex with men.2 after being exposed to monkeypox, a prodrome of fever, rash, and lymphadenopathy manifests in the wake of a 5-21 day incubation.3 the painful, vesiculopustular exanthem commonly starts on the face and disseminates centrifugally, affecting genitalia and palmoplantar surfaces as well.4 therefore, it is imperative for dermatologists to differentiate monkeypox from other febrile infectious exanthems due to the rapidly growing incidence and fatality rate. a 55-year-old latin male with a past medical history of psoriasis and hypertension presented to our clinic reporting a new acneiform eruption. he complained of painful ulcers around his genitalia and lesions on the hand, chest, and back of one-week duration. review of systems was notable for prodromal symptoms occurring three weeks prior including fever, myalgias, sore throat, and lethargy. the patient endorsed a monogamous relationship with a single male spouse, with frequent travel for work as an air steward. lastly, he admitted to frequent periods of substance abuse with subsequent memory impairment while traveling his various routes between spain and colombia. physical examination revealed scattered pustular, comedo-like papules on the anterior and posterior trunk as well as the dorsum of the right fifth digit. on the genitals, there were tender, punched-out ulcers in various stages of healing with white, friable rings on the margins and swollen erythema in the periphery. they appeared on the left side of the penile shaft, root, and mons pubis (figure 1). the initial differential diagnosis included haemophylis chancroid, acute varicella-zoster virus, syphilis, hiv, and monkeypox. he was prescribed 1% silvadene cream and 2g of azithromycin orally to cover both syphilis and chancroid. punch biopsy of the lesion showed a superficial and deep perivascular mixed inflammatory infiltrate with an overlying lichenoid inflammatory infiltrate with papillary dermal edema. the infiltrate was made up predominantly of neutrophils, admixed lymphocytes and eosinophils. the epidermis introduction case report https://paperpile.com/c/hqcuum/eexd https://paperpile.com/c/hqcuum/iptz https://paperpile.com/c/hqcuum/iptz https://paperpile.com/c/hqcuum/0j1s https://paperpile.com/c/hqcuum/vma1 skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 733 figure 1. papules, pustules, and ulcers on the torso, extremities, and genitals. figure 2. histopathology of the lesion showing a superficial and deep perivascular mixed inflammatory infiltrate predominantly of neutrophils, admixed lymphocytes and eosinophils with an overlying lichenoid inflammatory infiltrate with papillary dermal edema, vesicular changes containing numerous neutrophils and surrounding spongiosis, and follicular inflammatory involvement with numerous necrotic keratinocytes on 10x (left) and 40x (right) powers on hematoxylin and eosin stain. skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 734 showed intraepidermal vesicular changes containing numerous neutrophils and surrounding spongiosis. there were areas of follicular inflammatory involvement with numerous necrotic keratinocytes (figure 2). an infectious work-up was ordered, including viral culture for monkeypox, bacterial cultures, and hiv testing. monkeypox could not be confirmed on viral culture, as it was not sent on accepted viral transport media. however, the returned pathology description and negative results on the infectious panel, in the setting of the reported patient history, lead to a diagnosis of monkeypox. close follow-up showed resolution of most papules and ulcers. monkeypox was declared a global health emergency by the world health organization (who) on july 23, 2022, due to a rapid increase in reported cases. the case fatality rate of monkeypox is 3-6%, although higher in pediatric and immunocompromised patients.5 the first case of monkeypox infection was reported in the democratic republic of the congo in 1970, and subsequent cases were mainly reported in africa.6 there are two clades of monkeypox, the west africa clade and the congo basin clade. the current outbreak is from the west africa clade, which has milder symptoms than the congo basin clade.7 the social history and the presence of lymphadenopathy in the prodromal phase can favor monkeypox infection over other viral exanthems. the week-long sequential evolvement of macules, papules, vesicles, and pustules ultimately turns into crusted scabs and falls off between 7-14 days, indicating the end of the contagious period.4 however, serious complications such as sepsis, bronchopneumonia, encephalitis, and ocular infections may result in fatality.4 therefore, it is advised for individuals to follow the centers for disease control (cdc) and state/local public health guidelines regarding prevention, isolation, and symptom monitoring. post-exposure prophylaxis with early smallpox vaccination (acam200 and jynneos) has shown 85% efficacy in the prevention of monkeypox, possibly due to the long incubation period.8 the primary treatment of monkeypox is supportive care, however, medications including tecovirimat, cidofovir, vaccinia immune globulin, and brincidofovir have been utilized as potential treatments via expanded access investigational new drug protocol (ea-ind).4 in conclusion, dermatologists should have a high suspicion of monkeypox infection in individuals with acute onset of vesiculopustular rash and lymphadenopathy who have a recent travel history, prior exposure, and intimate contacts. early diagnosis may minimize spread, increase ease of contact tracing, and help manage expectations for disease course and symptoms. conflict of interest disclosures: none funding: none corresponding author: faraz yousefian, do 2925 aventura blvd, ste 205 aventura, fl 33180 email: yousefian.faraz@gmail.com references: 1. cdc. 2022 outbreak cases and data. centers for disease control and prevention discussion conclusion https://paperpile.com/c/hqcuum/6ncu https://paperpile.com/c/hqcuum/1xet https://paperpile.com/c/hqcuum/ku57 https://paperpile.com/c/hqcuum/vma1 https://paperpile.com/c/hqcuum/vma1 https://paperpile.com/c/hqcuum/3wzn https://paperpile.com/c/hqcuum/vma1 http://paperpile.com/b/hqcuum/eexd http://paperpile.com/b/hqcuum/eexd http://paperpile.com/b/hqcuum/eexd http://paperpile.com/b/hqcuum/eexd skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 735 https://www.cdc.gov/poxvirus/monkeypox/res ponse/2022/index.html (2022). 2. multi-country monkeypox outbreak in nonendemic countries: update. https://www.who.int/emergencies/diseaseoutbreak-news/item/2022-don388. 3. moore, m. j., rathish, b. & zahra, f. monkeypox statpearls. (2022). 4. bryer, freeman & rosenbach. monkeypox emerges on a global scale: a historical review and dermatological primer. j. am. acad. appl. nutr. 5. monkeypox. https://www.who.int/newsroom/fact-sheets/detail/monkeypox. 6. heymann, d. l., szczeniowski, m. & esteves, k. re-emergence of monkeypox in africa: a review of the past six years. br. med. bull. 54, 693–702 (1998). 7. multi-country monkeypox outbreak: situation update. https://www.who.int/emergencies/diseaseoutbreak-news/item/2022-don390. 8. adler, h. et al. clinical features and management of human monkeypox: a retrospective observational study in the uk. lancet infect. dis. 22, 1153–1162 (2022). http://paperpile.com/b/hqcuum/eexd http://paperpile.com/b/hqcuum/iptz http://paperpile.com/b/hqcuum/iptz https://www.who.int/emergencies/disease-outbreak-news/item/2022-don388 https://www.who.int/emergencies/disease-outbreak-news/item/2022-don388 http://paperpile.com/b/hqcuum/iptz http://paperpile.com/b/hqcuum/0j1s http://paperpile.com/b/hqcuum/0j1s http://paperpile.com/b/hqcuum/vma1 http://paperpile.com/b/hqcuum/vma1 http://paperpile.com/b/hqcuum/vma1 http://paperpile.com/b/hqcuum/vma1 http://paperpile.com/b/hqcuum/vma1 http://paperpile.com/b/hqcuum/6ncu http://paperpile.com/b/hqcuum/6ncu http://paperpile.com/b/hqcuum/1xet http://paperpile.com/b/hqcuum/1xet http://paperpile.com/b/hqcuum/1xet http://paperpile.com/b/hqcuum/1xet http://paperpile.com/b/hqcuum/1xet http://paperpile.com/b/hqcuum/1xet http://paperpile.com/b/hqcuum/1xet http://paperpile.com/b/hqcuum/1xet http://paperpile.com/b/hqcuum/ku57 http://paperpile.com/b/hqcuum/ku57 https://www.who.int/emergencies/disease-outbreak-news/item/2022-don390 https://www.who.int/emergencies/disease-outbreak-news/item/2022-don390 http://paperpile.com/b/hqcuum/ku57 http://paperpile.com/b/hqcuum/3wzn http://paperpile.com/b/hqcuum/3wzn http://paperpile.com/b/hqcuum/3wzn http://paperpile.com/b/hqcuum/3wzn http://paperpile.com/b/hqcuum/3wzn http://paperpile.com/b/hqcuum/3wzn http://paperpile.com/b/hqcuum/3wzn http://paperpile.com/b/hqcuum/3wzn http://paperpile.com/b/hqcuum/3wzn http://paperpile.com/b/hqcuum/3wzn impact of baseline smoking status and body mass index in patients with hidradenitis suppurativa treated with adalimumab or placebo in 2 phase 3 studies amit garg,1 hessel h van der zee,2 ziqian geng,3 gerit d mulder3 1department of dermatology, hofstra northwell school of medicine, hempstead, new york, usa; 2department of dermatology, erasmus medical center, rotterdam, the netherlands; 3abbvie inc., north chicago, illinois, usa presented at the fall clinical dermatology conference 36th anniversary • las vega, nevada • october 12 – 15, 2017 introduction • patients with hs who received treatment with ada had a greater clinical response than patients who received placebo, irrespective of baseline smoking status or bmi – the clinical response observed with ada was not affected by smoking status or bmi – patients may not have appropriately declared themselves as smokers, which may have affected the proportion of smokers who achieved clinical response • overall rates of teaes were similar in patients who received ada, regardless of smoking status or bmi disclosures objective methods results (continued) conclusions references • hidradenitis suppurativa (hs) is a chronic, inflammatory skin disorder associated with painful, deep-seated lesions in apocrine gland-bearing regions of the body1–4 • patients with hs commonly have a higher body mass index (bmi) and a large proportion smoke tobacco, but the effect of these factors on treatment outcomes has been controversial5 • originator adalimumab (ada) is an anti-tumor necrosis factor monoclonal antibody approved for the treatment of moderate-to-severe hs6 – results from 2 phase 3, placebo-controlled trials, pioneer i and pioneer ii, demonstrated the efficacy and safety of ada7 • this post hoc analysis evaluated the impact of baseline tobacco smoking status and bmi on the efficacy and safety of ada in 2 phase 3, double-blind studies (pioneer i and pioneer ii) participants • main inclusion criteria – adults (male and female) ≥ 18 years of age, with a diagnosis of hs ≥ 1 year prior to baseline – hs lesions present in at least 2 distinct anatomical areas (eg, left and right axilla, or left axilla and left inguinocrural fold), 1 of which was hurley stage ii or hurley stage iii – abscess and inflammatory nodule (an) count ≥ 3, where the an count equates to the sum of abscess and inflammatory nodules • main exclusion criteria – previous anti-tumor necrosis factor therapy or ada – other active skin disease or condition (eg, bacterial, fungal, or viral infection) that could interfere with assessment of hs – at baseline visit, draining fistula count > 20 – treatment for hs with oral antibiotics within 28 days of baseline visit (except for pioneer ii subjects on stable doxycycline or minocycline only), or analgesics or prescription topical treatment for hs within 14 days of baseline visit study design and treatment • data were integrated from the first 12 weeks (period a) of 2 phase 3 trials: pioneer i and ii • in both studies, patients were randomized (1:1) to receive ada or matching placebo (figure 1) – dose of ada was 160 mg at week 0, 80 mg at week 2, and 40 mg weekly starting at week 4 for 12 weeks (period a) • in pioneer ii, concomitant doxycycline or minocycline up to 100 mg twice daily was permitted if patients took the antibiotic for > 28 days before baseline and maintained a consistent dosing regimen during the study – concomitant antibiotic use was not permitted in pioneer i figure 1. study design n = 317 randomized n = 296 completed 12 weeks randomized n = 633 ada 40 mg weeklya placebo 0 12week: n = 316 randomized n = 300 completed 12 weeksrandomiza!on period a period b 3624 r era nd om iz a! on ada 40 mg weekly ada 40 mg every other week placebo placebo 2 double-blind, placebo-controlled trials (pioneer i & ii) astarting at week 4 following 160 mg at week 0 and 80 mg at week 2. in pioneer ii, patients who received placebo in period a received ada 40 mg weekly in period b. this analysis encompasses only the first 12 weeks, as depicted. ada = adalimumab. methods (continued) results patient assessment • patients were assessed in clinic at weeks 0, 2, 4, 8, and 12 • data from both trials were integrated to evaluate the effect of baseline smoking status (yes or no) or bmi (< 30 or ≥ 30 kg/m2) • the primary endpoint in both studies was hs clinical response (hiscr) – defined as ≥ 50% reduction in an count with no increase in abscess or draining fistula counts relative to baseline8 • adverse events and overall rates of treatment-emergent adverse events (teaes) were also reported statistical analysis • all randomized patients were included in the integrated efficacy analyses • treatment difference for the proportion of patients achieving hiscr was calculated using the cochranemantel-haenszel test (2 tailed, α = .05) – adjusted for study and baseline hurley stage • treatment by subgroup interaction, was calculated using a logistic regression with hiscr at week 12 as response variable, and treatment, subgroup, hurley stage, and treatment by subgroup interaction as factors participants: baseline smoking and bmi • this integrated analysis included 633 randomized patients (table 1) – of these, 596 patients completed the first 12 weeks of the study (ada, n = 300; placebo, n = 296) – 2 patients in the placebo group discontinued without receiving a dose • at baseline, the majority of patients reported smoking or had a bmi ≥ 30 (table 1) table 1. baseline demographics and disease characteristics characteristic ada (n = 316) placebo (n = 317) total (n = 633) age, years mean (sd) 35.5 (10.4) 37.0 (11.8) 36.2 (11.1) sex, n (%) female 199 (63.0) 218 (68.8) 417 (65.9) male 117 (37.0) 99 (31.2) 216 (34.1) duration of hs, n (median) < 9.18 years 163 (51.6) 153 (48.3) 316 (49.9) ≥ 9.18 years 153 (48.4) 164 (51.7) 317 (50.1) lesion counts, mean (sd) an 12.4 (10.3) 13.1 (13.0) 12.8 (11.7) abscesses 2.4 (3.1) 2.6 (3.5) 2.5 (3.3) inflammatory nodules 10.0 (9.2) 10.5 (11.9) 10.3 (10.6) non-draining fistulas 5.5 (11.7) 5.9 (8.5) 5.7 (10.2) draining fistulas 3.8 (4.7) 3.8 (4.8) 3.8 (4.8) hurley stage, n (%) ii 166 (52.5) 170 (53.6) 336 (53.1) iii 150 (47.5) 147 (46.4) 297 (46.9) modified sartorius score, mean (sd) 128.6 (109.9) 134.6 (93.2) 131.6 (101.8) bmi, kg/m2, n (%) < 30 133 (42.1) 113 (35.6) 246 (38.9) ≥ 30 182 (57.6) 202 (63.7) 384 (60.7) missing 1 (0.3) 2 (0.6) 3 (0.5) smoking status, n (%) yes 186 (58.9) 201 (63.4) 387 (61.1) no 130 (41.1) 115 (36.3) 245 (38.7) unknown 0 (0) 1 (0.3) 1 (0.2) ada = adalimumab; an = sum of inflammatory nodules and abscesses; bmi = body mass index; hs = hidradenitis suppurativa; sd = standard deviation. achievement of hiscr by smoking status • among those patients who smoked, a significantly greater proportion of patients who received ada achieved hiscr compared with patients who received placebo (91/186 vs 56/201, respectively; p < .001) (figure 2) • among nonsmokers, a significantly greater percentage of patients who received ada achieved hiscr compared with patients who received placebo (69/130 vs 29/115, respectively; p < .001) (figure 2) • the treatment effect is consistent across smoking subgoups with no significant treatment-by-subgroup interactions (p = .343) figure 2. achievement of hiscr in both smokers and nonsmokers who received ada †p < .001. achievement of hiscr by bmi • for patients with bmis < 30, hiscr was achieved by a significantly greater proportion of patients who received ada compared with placebo (72/133 vs 36/113, respectively; p < .001) (figure 3) • for patients with bmis ≥ 30, hiscr was achieved by significantly more ada-treated patients when compared with placebo (88/182 vs 48/202, respectively; p < .001) (figure 3) • the treatment effect is consistent across bmi subgroups with no significant treatment-by-subgroup interactions (p = .522) figure 3. achievement of hiscr in patients with bmi < 30 and bmi ≥ 30 who received ada †p < .001. treatment-emergent adverse events • the most frequently reported teaes in the ada population were hidradenitis, followed by headache, upper respiratory tract infections, and nasopharyngitis • patients who received ada reported fewer teaes than patients who received placebo, regardless of smoking status (table 2) or bmi category (table 3) • overall rates of teaes were similar in patients who received ada, regardless of smoking status or bmi table 2. treatment-emergent adverse event rates in smokers and nonsmokers characteristic yes no ada (n = 186) n (%) placebo (n = 201) n (%) ada (n = 130) n (%) placebo (n = 113) n (%) any ae 105 (56.5) 135 (67.2) 70 (53.8) 67 (59.3) any sae 4 (2.2) 7 (3.5) 2 (1.5) 4 (3.5) any ae leading to discontinuation of study drug 4 (2.2) 2 (1.0) 1 (0.8) 8 (7.1) any severe ae 11 (5.9) 15 (7.5) 6 (4.6) 4 (3.5) any infection 50 (26.9) 68 (33.8) 29 (22.3) 28 (24.8) any serious infection 1 (0.5) 1 (0.5) 1 (0.8) 1 (0.9) ae = adverse event; sae = serious adverse event. table 3. treatment-emergent adverse event rates by bmi category (< 30 and ≥ 30) characteristic < 30 ≥ 30 ada (n = 133) n (%) placebo (n = 113) n (%) ada (n = 182) n (%) placebo (n = 200) n (%) any ae 70 (52.6) 64 (56.6) 105 (57.7) 138 (69.0) any sae 2 (1.5) 3 (2.7) 4 (2.2) 8 (4.0) any ae leading to discontinuation of study drug 2 (1.5) 5 (4.4) 3 (1.6) 5 (2.5) any severe ae 6 (4.5) 7 (6.2) 11 (6.0) 12 (6.0) any infection 35 (26.3) 30 (26.5) 44 (24.2) 65 (32.5) any serious infection 1 (0.8) 1 (0.9) 1 (0.5) 1 (0.5) ae = adverse event; sae = serious adverse event. a garg has served as a consultant for abbvie inc., eli lilly, janssen, and pfizer. h van der zee has served as a consultant for abbvie and inflarx. z geng and gd mulder are full-time employees of abbvie, and may own stock and/or stock options. abbvie, funded this study and participated in the study design, study research, data collection, analysis and interpretation of data, and writing, reviewing, and approving this poster for presentation. all authors had access to the data; participated in the development, review, and approval of the poster; and agreed to submit the abstract and subsequent poster to eadv for consideration. editorial assistance, funded by abbvie, provided by kristy a grabowski, phd, of jb ashtin. 1. danby fw, margesson lj. dermatol clin. 2010;28:779–93. 2. hessam s, et al. j am acad dermatol. 2015;73:998–1005. 3. woodruff cm, et al. mayo clin proc. 2015;90:1679–93. 4. zouboulis cc, et al. dermatology. 2015;231:184–90. 5. zouboulis cc, et al. jeadv. 2015;29:619–44. 6. humira [package insert]. north chicago, il: abbvie inc; 2016. 7. kimball ab, et al. n engl j med. 2016;375:422-34. 8. kimball ab, et al. br j dermatol. 2014;171:1434–42. fc17posterabbviegargimpactofbaselinesmoking.pdf skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 343 short communication preference signaling in the dermatology residency match mckenzie a. dirr, ba, bs1, nicholas brownstone, md2, darrell rigel, md, ms3 1 medical university of south carolina, charleston, sc 2 national society for cutaneous medicine, new york, ny 3 department of dermatology, mount sinai icahn school of medicine, new york, ny the residency match, facilitated by the national resident matching program (nrmp) organization, which utilizes the association of american medical colleges (aamc) electronic residency application service (eras), facilitates the determination of where senior medical students will continue their education as resident physicians.1 created in 1952, the match is the culmination of a reciprocal interest between students and residency programs, whereby both entities rank prospects in order of interest. 1 as certain specialties have become inundated with interested applicants, alternative or adjunct methods for increasing match success have been implemented. 1 in the 2020-2021 cycle, otolaryngology initiated preference signaling (ps), in which students send a signal to a set number of residency programs to indicate a high level of interest in matching to that particular program.2,3 the purpose of initiating ps into medical residency match is to clarify a student’s intentions prior to the release of interview invitations. 2,3 participation in ps is optional, and students who choose to participate in ps are still encouraged to submit as many applications as they wish, while only schools receiving a signal are notified of the student’s action. 4 this notion has similarly been adopted by other specialties, including general surgery, internal medicine, and dermatology as part of the supplemental eras application.4 in august of 2021, the association of professors of dermatology announced participation in preference signaling in the 2021-2022 application cycle.5 within dermatology, each student is allotted three preference signals to distribute to various schools, which are not ranked in any particular order of interest.4 importantly, students are directed to not send a ps to programs at which they have done in-person rotations, including their home institution. 4 in an assessment of the 2022 supplemental application, the aamc published key findings which give insight into the state of residency application.6 within dermatology, 117 out of 135 u.s. programs and 93% of applicants chose to participate in the supplemental application.6 applicants chose to send signals based on various reasons, the most important factors being geographic location, quality of training, and program correspondence with career goals.6 it is important to evaluate the success of ps within each specialty, including dermatology, as well as areas for future improvement. as reported by the aamc key findings, onefourth of dermatology programs received up to 53% of preference signals from all applicants, indicating a skewed distribution of signals across programs.6 this may be due to skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 344 individual program factors, with more competitive residencies receiving more signals as a prerequisite for applicant consideration, or applicants sending signals to programs in which they are somewhat interested to increase chances of consideration.2 however, it is clear that ps played a major role in interview determination, with programs reporting ps usefulness in identifying unlikely candidates and determination of interview invitations.6 more studies are needed to determine the role preference signaling plays in the dermatology match itself, and in particular, the impact on final resident class determination. conflict of interest disclosures: none funding: none corresponding author: mckenzie a. dirr, ba, bs medical university of south carolina 96 jonathan lucas street suite 601, msc 617 charleston, sc 29425 phone: 843-792-2081 email: dirr@musc.edu references: 1. mott nm, carmody jb, marzano da, hammoud mm. what’s in a number? breaking down the residency match rate. the new england journal of medicine. 2022;386(17):1583-1586. doi:10.1056/nejmp2119716 2. gangal a, blalock tw. a perfect match: pros and cons of preference signaling in dermatology. journal of the american academy of dermatology. 2021;84(5):1504-1505. doi:10.1016/j.jaad.2020.12.050 3. chang cwd, pletcher sd, thorne mc, malekzadeh s. preference signaling for the otolaryngology interview market. the laryngoscope. 2021;131(3):e744-e745. doi:10.1002/lary.29151 4. association of american medical colleges. supplemental eras application guide. https://studentsresidents.aamc.org/media/12326/download. published august 2021. accessed may 2022. 5. association of professors of dermatology. dermatology apd statement on 2021-2022 application cycle. https://studentsresidents.aamc.org/media/12386/download. published august 20, 2021. accessed may 2022. 6. association of american medical colleges. aamc supplemental eras® application: key findings from the 2022 application cycle. https://www.aamc.org/media/58891/download. published february 2022. accessed may 2022. mailto:dirr@musc.edu https://students-residents.aamc.org/media/12326/download https://students-residents.aamc.org/media/12326/download https://students-residents.aamc.org/media/12386/download https://students-residents.aamc.org/media/12386/download https://www.aamc.org/media/58891/download acknowledgments all authors participated in the development of the poster and approved the final poster for presentation. editorial assistance in the development of this poster was provided by jessica donaldson of fishawack communications ltd, oxford, uk. this poster was previously presented at the european academy of allergy and clinical immunology congress, june 17–21, 2017, helsinki, finland. funding this study was funded by novartis pharmaceuticals canada inc. disclosures authors declare the following, real or perceived conflicts of interest: gs, jh, wg, cl, and why received honoraria as investigators and consultants. gs received honoraria as speaker of this corresponding study. oc, fdt, and lr are employees of novartis pharmaceuticals. contact information lenka rihakova – lenka.rihakova@novartis.com antonio vieira – antonio.vieira@novartis.com novartis pharmaceuticals canada: +1(514) 631 6775 study design • optima is an international, multicenter, randomized, open-label, noncomparator study of two doses of omalizumab treatment (150 mg and 300 mg) across two dosing periods • in the initial dosing period, patients receive omalizumab by subcutaneous injection, at the randomized dose, every 4 weeks (figure 1) • subsequent dosing is determined based on the patient’s uas7 response (figures 2 and 3) • patients are eligible for the optima study if they are adults diagnosed with ciu/csu and have been exhibiting symptoms for at least 6 months prior to the study despite concurrent nonsedating h 1 -antihistamine therapy • refractory to antihistamine therapy is defined as uas7 ≥16 (scale 0−42) and itch component of uas7 ≥8 (scale 0−21) despite treatment with an approved dose of nonsedating h 1 -antihistamine and no other concomitant ciu/csu treatment for at least 7 consecutive days conclusions • the optima study will allow better characterization of the appropriate omalizumab treatment regimen in patients with ciu/csu who relapse or are not well controlled after initial treatment, by answering the following questions: − if a patient is well controlled and therefore treatment is stopped, will the patient relapse? how long will it take to relapse? − if treatment is restarted, will the patient respond to retreatment? − if the patient does not respond to omalizumab 150 mg, will step-up therapy help? − if the patient does not respond to omalizumab 300 mg, will treatment extension help? objectives • primary: to assess the effect of optimized retreatment after relapse (defined as weekly urticaria activity score [uas7] ≥16) in patients with chronic idiopathic/spontaneous urticaria (ciu/csu) who were clinically well controlled (uas7 ≤6) following their first course of treatment with omalizumab • secondary: evaluation of dose step-up therapy in those who do not respond (uas7 >6) to an initial dose of omalizumab 150 mg; assessment of the time to relapse in patients who initially were well controlled (uas7 ≤6); and to evaluate the benefit of extending study treatment with omalizumab 300 mg in patients who are not yet clinically well controlled (uas7 ≤6) after 24 weeks • exploratory: evaluation of quality of life and occurrence of angioedema episodes design and rationale of the optima study: retreatment or step-up therapy with omalizumab in patients with chronic idiopathic/spontaneous urticaria (ciu/csu) gordon sussman,1 jacques hébert,2 wayne gulliver,3 charles lynde,4 william h. yang,5 olivier chambenoit,6 gretty deutsch,7 frederica detakacsy,8 lenka rihakova8 1department of medicine, university of toronto, toronto, on, canada; 2department of medicine, centre hospitalier de l’université laval, québec, qc, canada; 3faculty of medicine, memorial university of newfoundland, st. john’s, nl, canada; 4lynde institute for dermatology, markham, on, canada; 5ottawa allergy research corporation, university of ottawa medical school, ottawa, on, canada; 6novartis pharmaceuticals corporation, east hanover, nj, usa; 7previously novartis pharmaceuticals canada inc, dorval, qc, canada; 8novartis pharmaceuticals canada inc, dorval, qc, canada scan this qr code visit the web at: http://novartis.medicalcongressposters.com/default.aspx?doc=84898 mobile friendly e-prints 3 ways to instantly download an electronic copy of this poster to your mobile device or e-mail a copy to your computer or tablet text message (sms) text: q84898 to: 8nova (86682) us only +18324604729 north, central and south americas; caribbean; china +447860024038 uk, europe & russia +46737494608 sweden, europe standard data or message rates may apply. presented at the fall clinical dermatology conference, october 12–15, 2017, las vegas, nv, usa controlled at week 24 – uas7 ≤6 not controlled at week 24 uas7 >6 controlled at week 24 – uas7 ≤6 controlled/ mild uas7 ≤16 moderate/ severe uas7 ≥16 omalizumab 300 mg 0 4 8 12 16 2420 0 4 8 0 412 w e ll c o n tr o ll e d w it h o u t re la p s e weeks w e ll c o n tr o ll e d w it h r e la p s e n o t w e ll c o n tr o ll e d follow-up follow-up follow-up omalizumab 300 mg 1st dosing study treatment withdrawal 2nd dosing follow-up 0 4 8 figure 2. dosing scenarios for the omalizumab 300 mg treatment group. patients who are well controlled (uas7 ≤6) in the 24-week initial dosing period enter the 8-week withdrawal period and then the follow-up phase if they remain well controlled. if relapse (uas7 ≥16) occurs during withdrawal, patients are retreated in a second dosing period at the same dose (omalizumab 300 mg) for 12 weeks. if symptoms are not well controlled (uas7 >6) in the initial dosing period, then patients extend treatment for 36 weeks of continuous omalizumab 300 mg treatment. 0 4 follow-up follow-up follow-up follow-up controlled at every visit from week 8 to week 24 – uas7 ≤6 not controlled uas7 >6 controlled at every visit from week 8 to week 24 – uas7 ≤6 controlled/ mild uas7 ≤16 moderate/ severe uas7 ≥16 omalizumab 300 mg 0 4 8 12 16 2420 0 4 8 12 omalizumab 150 mg w e ll c o n tr o ll e d w it h o u t re la p s e w e ll c o n tr o ll e d w it h r e la p s e n o t w e ll c o n tr o ll e d 1st dosing study treatment withdrawal 2nd dosing 0 4 8weeks figure 3. dosing scenarios for the omalizumab 150 mg treatment group. patients who are well controlled (uas7 ≤6) in the 24-week initial dosing period enter the 8-week withdrawal period and then the follow-up phase if they remain well controlled. if relapse (uas7 ≥16) occurs during the withdrawal period, patients are retreated in a second dosing period at the same omalizumab 150 mg dose for 12 weeks. if symptoms are not well controlled (uas7 >6) during the initial omalizumab 150 mg dosing period, then patients step up to the omalizumab 300 mg dose at any protocol visit as early as week 8 to start the second dosing period. screen washout omalizumab 150 mg omalizumab 300 mg g ro u p a g ro u p b followup uas7 ≤6 uas7 <16 stop therapy omalizumab 300 mg omalizumab 150 mg r a n d o m iz a ti o n 4 :3 −5 to −1week 0 4 8 12 16 2420 0 4 8 12 0 4 uas7 >6 uas7 ≤6 uas7 <16 stop therapy omalizumab 300 mg omalizumab 300 mg uas7 ≥16 uas7 ≥16 uas7 >6 screen 1st dosing study treatment withdrawal 2nd dosing followup 0 4 8 figure 1. optima study design. the study includes 5 phases: screening; initial dosing period; withdrawal; a second dosing period for retreatment, dose step-up, or dose extension based on uas7 response; and follow-up. sample size and analysis sample size • the study has been planned to enroll and randomize a total of 320 patients, in a ratio of 4:3, to the doses of omalizumab 150 mg or 300 mg. the sample size is estimated on the basis of assessing the effect of retreatment following relapse (primary endpoint) primary endpoint • proportion of patients who achieved a uas7 ≤6 at the end of the second dosing period, after being clinically well controlled (uas7 ≤6) in the initial dosing period followed by relapse (uas7 ≥16) when treatment was discontinued secondary endpoints • difference in the uas7 between the start and the end of the second dosing period in patients who stepped up treatment from omalizumab 150 mg to 300 mg • the proportion of patients who were clinically well controlled (uas7 ≤6) at the end of the second dosing period in patients who stepped up treatment from omalizumab 150 mg to 300 mg • the time to relapse (uas7 ≥16) after withdrawal of omalizumab in patients who were clinically well controlled following their first course of omalizumab treatment • difference in the uas7 between the end of the initial dosing period and the end of the second dosing period in patients who extended treatment with omalizumab 300 mg • the uas7 change from baseline measured at the end of the initial dosing period in patients who received omalizumab 300 mg • the uas7 change from baseline measured at the end of the second dosing period in all patients • the proportion of patients who remain well controlled (uas7 ≤6) or who have achieved a uas7 =0 at week 8 of the initial dosing period versus week 8 of the second dosing period • the proportions of patients who remain clinically well controlled (uas7 ≤6) at any visit starting at week 8 of the initial dosing period until the end of the first dosing period uas7, weekly urticaria activity score. uas7, weekly urticaria activity score. uas7, weekly urticaria activity score. screen washout omalizumab 150 mg omalizumab 300 mg g ro u p a g ro u p b followup uas7 ≤6 uas7 <16 stop therapy omalizumab 300 mg omalizumab 150 mg r a n d o m iz a ti o n 4 :3 −5 to −1week 0 4 8 12 16 2420 0 4 8 12 0 4 uas7 >6 uas7 ≤6 uas7 <16 stop therapy omalizumab 300 mg omalizumab 300 mg uas7 ≥16 uas7 ≥16 uas7 >6 screen 1st dosing study treatment withdrawal 2nd dosing followup 0 4 8 references 1. clinicaltrials.gov – nct02161562. 2. sussman g, et al. design and rationale of the optima study: retreatment or step-up therapy with omalizumab in patients with chronic idiopathic/spontaneous urticaria (ciu/csu). fcdc 2017. poster. acknowledgments the complete optima study team comprised: 35 active sites in the following countries: argentina, brazil, canada, chile, dominican republic, guatemala, mexico, and panama; syreon clinical research for project management, data management, and medical writing; and novartis pharmaceuticals canada and novartis in participating countries. all authors participated in the development of the poster and approved the final poster for presentation. editorial assistance in the development of this poster was provided by jessica donaldson of fishawack communications ltd, oxford, uk. this poster was previously presented at the european academy of allergy and clinical immunology congress, june 17–21, 2017, helsinki, finland. funding this study was funded by novartis pharmaceuticals canada inc. disclosures authors declare the following, real or perceived conflicts of interest: gs, jh, wg, cl, and why received honoraria as investigators and consultants. gs received honoraria as speaker of this corresponding study. oc, av, fdt, and lr are employees of novartis pharmaceuticals. contact information lenka rihakova – lenka.rihakova@novartis.com antonio vieira – antonio.vieira@novartis.com novartis pharmaceuticals canada: +1(514) 631 6775 introduction • the optima (efficacy of optimized retreatment and step-up therapy with omalizumab in patients with chronic idiopathic/spontaneous urticaria [ciu/csu]; nct02161562) study was designed to address some of the key gaps in the knowledge of optimal ciu/csu treatment with omalizumab • owing to the intermittent nature of ciu/csu, physicians may want to consider stopping omalizumab treatment in patients who are symptom free for a period of time • symptoms may re-emerge after a period of treatment withdrawal; the primary objective of the study was therefore to determine the efficacy and safety of retreatment in patients who respond to an initial course of omalizumab objectives • four objectives were to be answered in optima: − if a patient is well controlled and therefore treatment is stopped, will the patient relapse? how long will it take to relapse? − if treatment is restarted, will the patient respond to retreatment? − if the patient does not respond to omalizumab 150 mg, will step-up therapy help? − if the patient does not respond to omalizumab 300 mg, will treatment extension help? • this poster will cover the first two questions methods study design • optima is a phase 3b, international, multicenter, randomized, open-label, noncomparator study.1 for details about the study design, please see the companion poster being presented at this congress (sussman et al. fcdc 2017)1,2 • patients with ciu/csu who were symptomatic despite h 1 -antagonists were randomized 4:3 to omalizumab 150 mg or 300 mg for 24 weeks (1st dosing period) • based on weekly urticaria activity scores (uas7), patients entered one of the following phases: treatment withdrawal (if uas7 ≤6), step-up to 300 mg (if 150 mg initially and uas7 >6 at weeks ≥8 to 24), or continued treatment for 12 more weeks (if 300 mg initially and uas7 >6 at week 24) conclusions • after being well controlled (uas7 ≤6), upon withdrawal 44.4% of patients on omalizumab 150 mg and 50.0% of patients on omalizumab 300 mg relapsed (uas7 ≥16) • the overall time to relapse for both dosages was 4.7 weeks • retreatment with both dosages is effective. overall, 87.8% of patients regained symptom control upon retreatment, after initially being well controlled and subsequent relapse 314 randomized patients omalizumab 300 mg 136 patients omalizumab 150 mg 178 patients discontinued 10 patients (5.6%) well controlled 27 patients (15.2%) not controlled – step-up 141 patients (79.2%) discontinued 5 patients (3.7%) well controlled 88 patients (64.7%) extended treatment 43 patients (31.6%) relapsers 12 patients (44.4%) nonrelapsers 15 patients (55.6%) nonrelapsers 44 patients (50.0%) relapsers 44 patients (50.0%) figure 3. disposition after withdrawal period – patients to receive retreatment 314 randomized patients omalizumab 150 mg, 178 patients omalizumab 300 mg, 136 patients figure 2. patient randomization ratio • if patients relapsed (uas7 ≥16) upon withdrawal, they were retreated with their starting dose for 12 weeks inclusion criteria • men or women at least 18 years of age • diagnosis of ciu/csu and the presence of symptoms for ≥6 months prior to the screening visit • patients must have been on an approved dose of nonsedating h 1 -antihistamine for ciu/csu, and no other concomitant ciu/csu treatment, for at least the 7 consecutive days immediately prior to the randomization visit and must have documented current use on the day of the randomization visit • uas7 ≥16 (scale 0−42) and itch component of uas7 ≥8 (scale 0−21) during 7 days prior to randomization exclusion criteria • patients with a clearly defined underlying etiology for chronic urticaria other than ciu/csu • patients with urticarial vasculitis, urticaria pigmentosa, erythema multiforme, mastocytosis, hereditary or acquired angioedema, lymphoma or leukemia, active atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus, or other skin disease associated with itch that could interfere with study outcomes • patients with a history of malignancy of any organ system • patients should stay on same approved dose of nonsedating h 1 -antihistamine during all trial duration. no rescue medication allowed results baseline characteristics omalizumab retreatment of patients with chronic idiopathic urticaria/spontaneous urticaria (ciu/csu) following return of symptoms: primary results of the optima study gordon sussman,1 jacques hébert,2 wayne gulliver,3 charles lynde,4 william h. yang,5 olivier chambenoit,6 antonio vieira,7 frederica detakacsy,7 lenka rihakova7 1department of medicine, university of toronto, toronto, on, canada; 2department of medicine, centre hospitalier de l’université laval, québec, qc, canada; 3faculty of medicine, memorial university of newfoundland, st. john’s, nl, canada; 4lynde institute for dermatology, markham, on, canada; 5ottawa allergy research corporation, university of ottawa medical school, on, canada; 6novartis pharmaceuticals corporation, east hanover, nj, usa; 7novartis pharmaceuticals canada inc., dorval, qc, canada table 1. demographics and baseline characteristics characteristic omalizumab 150 mg (n=178) omalizumab 300 mg (n=136) overall (n=314) age, mean (range), years 46.7 (18–79) 45.8 (20–78) 46.3 (18–79) gender, % male female 27.0 73.0 27.2 72.8 27.1 72.9 race, % white asian black am. indian/alaska native other 76.4 8.4 5.6 1.1 8.4 83.1 7.4 4.4 2.2 2.9 79.3 8.0 5.1 1.6 6.1 time to ciu/csu symptoms, n (%) ≤1 year >1–≤2 years >2–10 years >10 years 28 (15.7) 25 (14.0) 84 (47.2) 41 (23.0) 22 (16.2) 25 (18.4) 54 (39.7) 35 (25.7) 50 (15.9) 50 (15.9) 138 (43.9) 76 (24.2) baseline uas7, mean (range) 29.7 (16.0–42.0) 30.0 (16.0–42.0) 29.8 (16.0–42.0) # prior medications used for ciu/csu, mean (range) 1.8 (0.0–12.0) 2.1 (0.0–8.0) 1.9 (0.0–12.0) ciu/csu, chronic idiopathic/spontaneous urticaria; uas7, weekly urticaria activity score. table 2. mean time to replase omalizumab 150 mg omalizumab 300 mg overall 4.8 weeks 4.7 weeks 4.7 weeks scan this qr code visit the web at: http://novartis.medicalcongressposters.com/default.aspx?doc=44671 mobile friendly e-prints 3 ways to instantly download an electronic copy of this poster to your mobile device or e-mail a copy to your computer or tablet text message (sms) text: q44671 to: 8nova (86682) us only +18324604729 north, central and south americas; caribbean; china +447860024038 uk, europe & russia +46737494608 sweden, europe standard data or message rates may apply. presented at the fall clinical dermatology conference, october 12–15, 2017, las vegas, nv, usa figure 1. study design for retreated patients uas7, weekly urticaria activity score. 40 35 30 25 20 m e a n ( ± 9 5 % c i) u a s 7 15 10 5 0 day 0 month 1 month 2 month 3 1st dosing period month 4 month 5 month 6 month 7 month 8 month 9 month 10 month 11 omalizumab 150 mg (n=12) 29.8 1.3 3.8 29.4 omalizumab 300 mg (n=37*) 30.1 1.2 28.3 2.3 withdrawal period 2nd dosing period figure 4. mean uas7 of retreated patients throughout the study *7 out of 44 patients on omalizumab 300 mg did not complete the 2nd dosing period or did not submit the participant diary as per protocol. ci, confidence interval; uas7, weekly urticaria activity score. p a ti e n ts ( % ) 83.3% omalizumab 150 mg (n=12) 89.2% omalizumab 300 mg (n=37*) 87.8% overall (n=49) 100 75 50 25 0 figure 5. proportion of patients regaining symptom control upon retreatment *7 out of 44 patients on omalizumab 300 mg did not complete the 2nd dosing period or did not submit the participant diary as per protocol. error bars represent 95% confidence intervals. skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 740 short communication treatment of cutaneous lesions in a case of blue rubber bleb nevus syndrome sokhna seck, ms1, taylor a. bullock, md2, shilpi khetarpal, md2 1cleveland clinic lerner college of medicine, case western reserve university, cleveland, oh 2department of dermatology, cleveland clinic foundation, cleveland, oh blue rubber bleb nevus syndrome (brbns) is a rare vascular disorder characterized by distinct venous malformations in various organ systems. common organ systems affected include the skin, liver, spleen, heart, eye, and central nervous system. patients often present early in life with blue, compressible, mucocutaneous nodules that may be painful. treatment of brbns is largely symptomatic; surgical interventions can be performed for symptomatic lesions. a 27-year-old female with a history of brbns presented for painful lesions on the plantar surfaces of the feet (figure 1) and a new growth on the left labia majora (figure 2). vascular-appearing papules on the right lateral thigh and overlying the right scapula (figure 3) were also present. she was initially diagnosed with brbns at the age of 15, when her pediatrician recognized the characteristic look of a few of her blue lesions and initiated further workup. since then, vascular malformations had been found on imaging in the brain, spleen, liver, and retroperitoneum. sclerotherapy and sirolimus had been attempted for intraabdominal vascular malformations without success, before ultimately having a liver lesion surgically removed. she also had developed many painful cutaneous lesions on the hands, legs, posterior neck, back, pelvis, and sacral area, many of which had been surgically removed. pathology for these demonstrated venous malformations, cavernous hemangiomas, lymphangiomas and hemangiomas. the patient was instructed to undergo routine imaging to monitor for the growth of existing lesions and occurrence of new lesions. the plantar abstract blue rubber bleb nevus syndrome (brbns), sometimes called bean syndrome, is a rare sporadic congenital vascular disorder characterized by multiple venous malformations in various organ systems, most commonly the skin and gastrointestinal tract. the presence of characteristic skin lesions is often the first suggestion of this diagnosis, though chronic anemia and intestinal bleeding are also commonly present. we report a case of a patient with painful lesions on the plantar surfaces of the feet and a new cutaneous growth on the left labia majora. the plantar lesions were treated with nd:yag laser and the lesion on the labia majora was removed with a shave biopsy. introduction case report skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 741 lesions were treated with nd:yag laser. the friable vascular papule on the labia majora was removed via shave biopsy, with pathology results showing a venous malformation in the setting of brbns. figure 1. (a, b) tender blue papules on the bilateral plantar surfaces of the feet. figure 2. venous malformation with the morphology of a friable plaque on the left labia majora. blue rubber bleb nevus syndrome (brbns), sometimes called bean syndrome, is a sporadic congenital disorder with unknown etiology, although autosomal dominant inheritance has also been described.1 the most commonly affected organs are the skin and the gastrointestinal tract. intestinal bleeding and secondary iron deficiency anemia is the most common complication and the presence of skin lesions is often the first suggestion of this diagnosis in patients with chronic anemia.2 all venous malformations are present at birth, though they may not be clinically apparent until later in life. venous malformations typically cause pain due to thrombosis and can increase in size in response to trauma, thrombosis, or hormones. management of brbns should involve an interdisciplinary team approach with hematology, dermatology, gastroenterology, and surgery. iron replacement and frequent blood transfusions may be required. symptomatic venous malformations can be treated with laser therapy, sclerotherapy, or surgical excision. figure 3. blue vascular papules on the right lateral thigh (a) and overlying the right scapula (b). discussion conclusion skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 742 brbns is a rare vascular disorder with venous malformations in the skin and/or internal organs. patient education and lifelong monitoring of lesions are essential. surgical interventions, including lasers, can be used to treat cutaneous venous malformations. conflict of interest disclosures: none funding: none corresponding author: sokhna seck, ms cleveland clinic lerner college of medicine 9501 euclid ave. cleveland, oh 44195 email: secks@ccf.org references: 1. nahm wk, moise s, eichenfield lf, paller as, nathanson l, malicki dm, friedlander sf. venous malformations in blue rubber bleb nevus syndrome: variable onset of presentation. j am acad dermatol. 2004 may;50(5 suppl):s101-6. 2. jin xl, wang zh, xiao xb, huang ls, zhao xy. blue rubber bleb nevus syndrome: a case report and literature review. world j gastroenterol. 2014 dec 7;20(45):17254-9. doi: 10.3748/wjg.v20.i45.17254. pmid: 25493043; pmcid: pmc4258599. 3. liu q, chen yp, li ym. blue rubber bleb nevus syndrome: a report of one case associated with recurrent epistaxis. chin med j (engl). 2007 apr 20;120(8):731-3. sonidegib efficacy and safety in patients with locally advanced basal cell carcinoma based on tumor aggressiveness michael r. migden, md1, and reinhard dummer, md2 1departments of dermatology and head and neck surgery md anderson cancer center, houston, tx, usa 2department of dermatology, university of zurich hospital, zurich, switzerland background basal cell carcinomas (bccs) can be categorized as aggressive or nonaggressive based on their histology1,2 – most bccs have nonaggressive histology, including superficial and nodular subtypes2 – aggressive subtypes (eg, micronodular, infiltrative, or sclerosing) are rarer but tend to have a higher rate of recurrence1,2 sonidegib (lde225) is a hedgehog (hh) pathway inhibitor approved for the treatment of patients with locally advanced bcc (labcc) not amenable to surgery or radiotherapy3-5 – sonidegib was approved based on results from the phase 2 basal cell carcinoma outcomes with lde225 treatment (bolt) study (nct01327053), which included patients with aggressive or nonaggressive labcc subtypes6 objective in patients with labcc regardless of tumor aggressiveness, durable tumor responses were observed – these results are significant, given the higher rate of recurrence and higher chance of subclinical spread associated with aggressive labcc subtypes here we present the efficacy and safety of sonidegib 200 mg in patients with labcc, based on tumor aggressiveness, from the bolt 30-month analysis methods bolt was a multicenter, randomized, double-blind, phase 2 study that enrolled patients with labcc (aggressive or nonaggressive) or metastatic bcc (mbcc; figure 1) patients with labcc not amenable to curative surgery or radiotherapy were randomized in a 1:2 ratio to 200 mg or 800 mg once daily (qd); only results from the 200-mg qd dose will be discussed here objective response rate (orr: confirmed complete response [cr] + partial response [pr]). duration of response, and progression-free survival (pfs) were assessed according to stringent criteria, defined as modified response evaluation criteria in solid tumors (mrecist; figure 2), by central review – overall survival (os) was also assessed safety was assessed until 30 days after the final treatment; common terminology criteria for adverse events (ctcae) v4.03 guidelines were used to evaluate adverse events (aes)6 figure 1: bolt study design screening/ baseline treatment follow-up (after treatment discontinuation) patientsa: (1) labcc (2) mbccc sonidegib 200 mg daily • labcc n = 66 • mbcc n = 13 sonidegib 800 mg daily • labcc n = 128 • mbcc n = 23 stratificationb randomization (1:2) treatment until: • disease progression • unacceptable toxicity • death • discontinuation from the study for any other reason (1) tumors assessed q8w during year 1 and q12w thereafter until disease progression (2) information collected on any further anticancer therapy received (3) aes collected until 30 days after last dose of study treatment (4) survival follow-up q12w until patient died, was lost to follow-up, or withdrew consent (and at the time of the final analysis) apatients treated with previous sonidegib or other hedgehog pathway inhibitors were excluded. bstratification was based on stage, history, disease histology for patients with labcc (aggressive vs nonaggressive), and geographic region. aes, adverse events; labcc, locally advanced basal cell carcinoma; mbcc, metastatic basal cell carcinoma; q8w, every 8 weeks; q12w, every 12 weeks. evaluated by: a d aassessed by central review per recist v1.1.9. bstandard and annotated color photography assessed per who criteria.9 partial response ≥50% reduction in the sum of products of perpendicular diameters from baseline; progressive disease ≥25% increase in the sum of products of perpendicular diameters from the lowest point. chistology was assessed in multiple biopsies surveying the lesion area. dcomposite overall response was determined by an independent review committee that reread all available data, including histology reports for labcc. cr, complete response; labcc, locally advanced basal cell carcinoma; mrecist, modified response evaluation criteria in solid tumors; mri, magnetic resonance imaging; who, world health organization. figure 2: stringent tumor response evaluation criteria results 66 patients with labcc received 200 mg qd sonidegib – of these, 37 (56%) patients had aggressive labcc subtypes and 29 (44%) had nonaggressive subtypes 92% of patients were no longer receiving sonidegib as of the cut-off date for the 30-month analysis median duration of exposure was 11.1 months most common reasons for discontinuation were aes (29%) and progressive disease (37%) efficacy orrs per central review were similar for patients with aggressive or nonaggressive labcc subtypes (table 1; figure 3) – in patients with aggressive subtypes, orr per central review was 59% in the 200-mg treatment arm – in patients with nonaggressive subtypes, orr per central review was 52% in the 200-mg treatment arm table 1: sonidegib efficacy in labcc at 30 months sonidegib 200 mg qd central review aggressive a (n = 37) nonaggressive b (n = 29) best overall response, n (%) • crc • prc • sd • pd • unknown 2 (5) 20 (54) 12 (32) 1 (3) 2 (5) 1 (3) 14 (48) 11 (38) 0 3 (10) orr (95% ci); % cr, % pr 59 (42-75); 5,54 52 (32.5-71); 3, 48 dcr, %d 92 90 dor, no. of eventse/ responders; median (95% ci), mo 7/22; 26.1 (not estimable) 4/15; not reached kaplan-meier-estimated median (95% ci), moe 26.1 (ne) ne pfs, no. of events; median (95% ci), mo 11; 22.1 (not estimable) 5; not reached os, median (95% ci), mo; 2-yr os (95% ci), % not reached; 92 (71-98) not reached; 95 (68-99) aincludes micronodular, infiltrative, multifocal, basosquamous, and sclerosing labcc; bincludes nodular and superficial labcc; crequired confirmation on repeat assessments >4 weeks apart; dcr+pr+sd; ekm-estimated time from first cr or pr until disease progression or death due to any cause (among responders). cr, complete response; dcr, disease control rate; dor, duration of response; orr, overall response rate; os, overall survival; pr, partial response; pfs, progression-free survival, qd, once daily; sd, stable disease. table 2: pfs and os in patients by labcc subtype sonidegib 200 mg qd aggressive (n = 37) nonaggressive (n = 29) pfs events, n (%) 11 (30) 5 (17) km-estimated media pfs duration (95% ci), months 21.1 (ne) ne deaths, n (%) 4 (11) 1 (3) km-estimated 2-uear os (95% ci), % 92 (71-98) 9 (68-99) ci, confidence interval; km, kaplan-meier; labcc, locally advanced bcc; os, overall survival; pfs, progression-free survival progression and survival pfs and os were similar for patients with aggressive or nonaggressive labcc subtypes (table 2) overall, 5 deaths in patients with labcc in the 200-mg arm were reported by the data cutoff date median os was not reached for either histological subgroup in either arm safety the observed safety profile of sonidegib remained similar to that of previous analyses, with the 200-mg dose continuing to show a favorable profile7,8,10 >50% of patients with labcc experienced grade 1/2 aes the most common aes of any grade among patients with labcc were muscle spasms, alopecia, dysgeusia, and nausea (figure 4) there were no treatment-related deaths there were no significant differences noted between the subtypes conclusions with 30 months of follow-up, patients with aggressive or nonaggressive labcc subtypes experienced durable responses when given sonidegib 200 mg daily the efficacy of sonidegib was similar for patients with aggressive or nonaggressive labcc subtypes in this analysis no new safety concerns were detected, and sonidegib 200 mg demonstrated a good benefit– risk profile together, these data support the use of sonidegib 200 mg daily in patients with labcc regardless of tumor aggressiveness, in accordance with local guidelines references 1. leboit pe, et al, eds. who classification of tumours: pathology and genetics of skin tumours. lyon, france: iarc press; 2006. 2. kuijpers di, et al. am j clin dermatol. 2002;3:247-259. 3. swissmedic. human and veterinary medicines. www. swissmedic.ch/arzneimittel/00156/00221/00222/00230/ index.html?lang=en. accessed august 10, 2016. 4. european medicines agency. chmp summary of opinion for odomzo. www.ema.europa.eu/docs/ en_gb/document_library/ summary_of_opinion_-_initial_authorisation/human/ 002839/ wc500188762.pdf. accessed august 10, 2016. 5. odomzo (sonidegib) package insert. cranbury, nj: sun pharmaceutical industries ltd; 2017. 6. national cancer institute. common terminology criteria for adverse events (ctcae). version 4.0. http://evs. nci.nih.gov/ ftp1/ctcae/ctcae_4.03_2010-06-14_quickreference_5x7. pdf. accessed august 10, 2016. 7. migden m, et al. lancet oncol. 2015;16:716-728. 8. rodon j, et al. clin cancer res. 2014;20:1900-1909. 9. world health organization. who handbook for reporting results of cancer treatment. http://whqlibdoc.who.int/offset/ who_offset_48.pdf. accessed march 30, 2016. 10. dummer r, et al. j am acad dermatol. 2016;75:113-125.e5. acknowledgements medical writing and editorial support were provided by beverly e. barton, phd, of scioscientific, llc. disclosures funding source: this study was funded by novartis pharmaceuticals corporation. novartis pharmaceuticals corporation was involved in the design and conduct of the study; collection, management, analysis, and interpretation of data; and preparation, review, and approval of the data. the decision to submit the data for presentation was made by sun pharmaceutical industries ltd. dr migden has participated on advisory boards and received honoraria from genentech incorporated, novartis pharmaceuticals corporation, sun pharmaceutical industries ltd, and eli lilly & company. dr dummer has received research funding from novartis pharmaceuticals corporation, merck sharp & dohme, bristolmyers squibb, roche, and glaxosmithkline. he has served as a consultant or participated on advisory boards for novartis pharmaceuticals corporation, merck sharp & dohme, bristolmyers squibb, roche, glaxosmithkline, amgen, and takeda. figure 3: best overall response by labcc subtype at 30 months figure 4: adverse events regardless of cause in ≥20% of patients with labcc dcr, disease control rate; labcc, locally advanced bcc; orr, objective response rate. ae, adverse event; ck, creatinine kinase; labcc, locally advanced bcc. 0% 20% 40% 60% 80% 100% p at ie nt s, % aggressive n = 37 nonaggressive n = 29 5% 3% 32% 54% 5% 10% 38% 48% 3% dcr: 90% orr: 52% dcr: 92% orr: 59% complete response partial response stable disease progressive disease unknown sonidegib 200 mg 45 8 3 38 14 36 12 24 12 2 18 8 6 15 9 3 2 17 11 2 23 3 2 8 9 2 15 3 11 2 muscle spasms alopecia dysgeusia nausea weight decrease ck increase fatigue diarrhea appetite decrease myalgia vomiting 0 10 20 30 40 50 60 70 80 patients, % a e s in ≥ 2 0% o f p at ie nt s w ith la b c c tr ea te d w ith s on id eg ib 2 00 m g figure 4: adverse events regardless of cause in ≥20% of patients with labcc 56% 52% 47% 38% 32% 29% 29% 27% 18% 18% 12% all grades ae, adverse event; ck, creatinine kinase; labcc, locally advanced bcc grade 1 grade 2 grade 3 grade 4 presented at 2017 fall clinical dermatology conference®, las vegas, nv, usa fc17postersunmigdensonidegibefficacy.pdf skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 368 clinical management recommendations expert panel discussion among psoriasis and psychodermatology specialists: how best to manage depressed psoriasis patients with brodalumab quinn thibodeaux, md1, rick fried, md, phd2, gary goldenberg, md3, george han, md4, sylvia hsu, md5, leon kircik, md6, melissa knuckles, md7, mark lebwohl, md4, graham h. litchman, do, ms8, andrea murina, md9, ryan rivera-oyola, ms4, jeffrey weinberg, md4, jashin j. wu, md10, john koo, md1 1university of california san francisco, department of dermatology, san francisco, ca 2yardley dermatology associates; yardley clinical research associates 3goldenberg dermatology; icahn school of medicine at mount sinai, department of dermatology, new york, ny 4icahn school of medicine at mount sinai, department of dermatology, new york, ny 5temple university lewis katz school of medicine, department of dermatology, philadelphia, pa 6mount sinai medical center, new york, ny; indiana university medical center, indianapolis, in 7m. l. f. knuckles dermatology, corbin, ky; m. l. f. knuckles dermatology richmond, ky; adventhealth hospital, manchester, ky 8national society for cutaneous medicine, new york, ny 9tulane university school of medicine, department of dermatology, new orleans, la 10dermatology research and education foundation, irvine, ca depression is a well-established comorbidity of psoriasis. recent epidemiologic studies have consistently found elevated rates of depression in psoriatic populations when compared to control groups.1,2 despite its prevalence, dealing with depression may be unfamiliar territory for many dermatologists. when treating a psoriasis patient with depression, some providers may be overly conservative in treatment, in that they may utilize slower-acting systemic agents or rely on only topical medications or phototherapy for moderate-to-severe disease. however, patients who are severely impacted psychologically by their psoriasis may warrant more aggressive therapy, utilizing one of the highly effective and rapidly-acting agents available. to help practitioners better manage this common therapeutic challenge, a group of psoriasis and psychodermatology experts convened to formulate a set of recommendations on how patients with psoriasis and depression may be better cared for in a dermatologic setting. this group included a board-certified psychiatrist, a licensed clinical psychologist, and multiple dermatologists with expertise in treating psoriatic disease and who have studied mental health issues related to psoriasis. to the authors’ knowledge, this type of multidisciplinary workgroup focusing on psoriasis and depression has never before been assembled. the following recommendations are intended to be practical, realistic, and targeted to busy dermatology practitioners. they are not intended to be guidelines, but instead represent the consensus opinions of this diverse panel of experts. introduction skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 369 if the presence of significant depression is suspected in a patient with psoriasis, how do we broach the topic and when do we consider referral? one approach to inquiring about depression is to take a similar strategy as with other psoriatic comorbidities. for example, psoriatic arthritis is a common comorbid disorder for which patients are frequently screened, and the same should be true for depression. several screening questionnaires are available for depression, including the hospital anxiety and depression scale (hads), patient health questionnaire-9 (phq-9), and hamilton depression rating scale (ham-d); however, these questionnaires are often impractical in a hectic dermatology practice. one of the easiest screening tools is a review-of-systems questionnaire that allows patients to report their depression, joint pain, or other symptoms prior to being seen. if practitioners note a check in the “depressed” or “altered mood” box, or if they suspect depression for any other reason, a direct and to the point inquiry is recommended to initiate discussion. although not necessarily required of dermatologists, it may be helpful to ask patients if their depression is secondary to psoriasis, or if there are other underlying factors involved which may predate their psoriasis. if the depression is purely secondary to psoriasis, then more aggressive treatment may be warranted; however, if the depression is primary or a combination of primary and secondary, then consultation with a mental health provider could also be helpful. it is the consensus of the panel that the role of the dermatologist is to properly screen patients in order to identify the cases where depression is relevant, but not to officially diagnose or treat depression. dermatologists are ideally situated to screen and properly refer for the formal management of psoriatic comorbidities. an identical strategy should be taken with depression as is already common practice for psoriatic arthritis. if a patient with psoriasis endorses joint pain, swelling, or stiffness, a dermatologist considering systemic therapy will likely take this into account when choosing a therapeutic agent, in addition to suggesting a rheumatologic referral. in the analogous case of coexistent depression, the treating dermatologist should take into account the patient’s psychological wellbeing when considering therapy options, in addition to discussing referral to a mental health provider. the initiation of an agent that is highly effective with a quick onset of action is most desirable, especially if the patients’ depressive symptoms are purely secondary to their psoriatic disease. this strategy of timely referral and rapidly improving symptoms is most critical when a patient’s psoriatic disease is contributing to severe depression or if there is any suggestion of suicidality, including suicidal ideations, behaviors, or plans. after a proper referral has been considered, how do we choose the best therapeutic option? when considering a therapeutic agent for the depressed psoriasis patient, highly effective and quickly acting treatment options are preferred. for many patients, depression is to a large extent due to the recommendation 1 recommendation 2 skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 370 disfiguration and reduction in quality of life caused by their psoriasis. in some cases, psoriasis may in fact be the entire underlying reason for their depression. separating depression secondary to psoriasis from primary, intrinsic depression is often as simple as asking the patient. direct questions such as “how does your psoriasis make you feel?” or “do you think your depression is related to your psoriasis?” are typically well-received by patients and will offer the provider some insight into the nature of the patient’s psychological comorbidity. regardless of the primary or secondary nature of depression, the more psychologically distressed the patient, the more essential it is that his or her psoriasis symptoms are resolved quickly. the il-17 inhibitors are some of the most effective and fastest acting therapeutic options available and are all useful for rapidly controlling psoriatic disease. one agent in this group, brodalumab (siliqtm), has a black box warning regarding suicidal ideation and behavior, which may dissuade some practitioners from prescribing it to a potentially depressed patient. however, as long as the patient has previously failed another systemic agent for psoriasis, brodalumab can be an excellent choice due to its speed of onset and high rates of clearance. in regard to the three cases of adjudicated suicide (i.e. the deaths that a panel of independent experts determined were consistent with suicide after reviewing all available data) that occurred during clinical development, the united states food and drug administration states in the brodalumab package insert that the “causal association between treatment with siliq and increased risk of suicidal ideation and behavior has not been established.”3 this consensus panel of psoriasis and psychodermatology experts concur with the fda’s assessment and conclusion for the following reasons: 1. the box warning was developed in response to three confirmed suicides that occurred from a total of 4,464 exposed patients throughout brodalumab’s psoriasis development program.4 two additional suicides occurred in 1,168 patients in trials for other conditions.5 2. there was no chronological association between initiation of brodalumab and the completion of suicide, with the acts occurring 140, 329, and 845 days after the subjects’ first dose.4 3. over the first 12 weeks of one of the pivotal phase 3 trials, treatment with brodalumab reduced patients’ depression and anxiety, as documented by their hospital anxiety and depression scores. this response was statistically significant when compared to placebo groups.6 4. the three subjects who completed suicide had significant concurrent life stressors that may have contributed to their actions, including financial hardship, acute social isolation, and likely pending incarceration.4 a fourth overdose occurred in a patient who mixed opiates and alcohol; however, this patient did not leave a suicide note or any other indication that the overdose was intentional. 5. throughout the 52-week, controlled, head-to-head comparison period of the phase 3 trials, numerically higher rates of suicidal ideation and behavior (sib) were seen in the ustekinumab-treated group than in the brodalumab-treated group.4 skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 371 6. il-17 and the brodalumab molecule have very little ability to cross the blood-brain barrier. brodalumab has a molecular weight of 144 kda, and it is generally accepted that molecules larger than 0.4 kda are unable to cross the blood-brain barrier.7 7. no link between the blockade of il-17 signaling and depression has been established, and human studies show no consistent association between il-17 and suicidal ideation and behavior.8 8. the brodalumab development program did not exclude patients with a history of psychiatric disorders or other risk factors for suicidality, in contrast to the development programs for many other therapeutic agents for psoriasis. 9. despite the inclusion of patients with psychiatric disorders and sib risk factors, rates of serious psychiatric adverse events in the brodalumab clinical trials are comparable to the rates reported for other psoriasis treatments.9 10. during the clinical trials of brodalumab in the treatment of rheumatoid arthritis and crohn’s disease, no convincing signals regarding depression or sib have arisen; however, one case of attempted suicide was reported during the phase 2 trial for rheumatoid arthritis.10,11 this panel of psychodermatology and psoriasis experts have collaborated to release the following consensus statement: depression is prevalent in psoriasis. multiple studies have shown that suicidality is increased in patients with psoriasis. depression, suicidal ideation, and suicide are prevalent and increasing problems in society. it’s the disease, not the drug. we should always evaluate and consider the mental health of our patients. it is our conclusion that treatment of psoriasis does not increase or cause depression but instead plays an important role in ameliorating depression. timely institution of highly and rapidly effective treatment may be critical in patients with significant negative psychological consequences of psoriasis. it is our consensus that the treatment of psoriasis with medications, including brodalumab, does not increase or cause depression, but instead plays an important role in ameliorating depression. of the recommendations expressed in this article, the most notable is that the timely institution of highly and rapidly effective treatment may be critical in patients with significant negative psychological consequences of psoriasis. as previously stated, this panel concluded that the role of the dermatologist is not to officially diagnose or treat depression, but instead to focus on proper screening and referral. it is also recommended that dermatologists tailor their treatment of depressed patients with psoriasis to include agents that are highly effective and rapidly acting. there are many factors to consider when selecting a psoriasis therapy.12,13 it is the hope of this panel that these recommendations will provide a practical framework for managing patients with psoriatic disease and comorbid depression. conclusion skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 372 conflict of interest disclosures: dr. thibodeaux has no relevant conflicts of interest. dr. fried has no relevant conflicts of interest. dr. goldenberg is a consultant and speaker for abbvie, amla, bayer, celgene, dermira, leo, novartis, pharmaderm, pfizer, and regeneron/sanofi. he is a consultant for allergan, amgen, almirall, castle, eclipse, galderma, genentech, gsk/stiefel, intraderm, isdin, janssen, menlo, ranbaxy, scibase, suneva, teva, valeant/ortho dermatologic, and verrica. he is a speaker for merz and on the board of directors of verrica. dr. han has no relevant conflicts of interest. dr. hsu has been an investigator for celgene and novartis and an advisor for janssen, ortho dermatologics, and menlo therapeutics. dr. kircik is a speaker for abbott laboratories, allergan, amgen, assos pharma, astellas pharma us, inc., cipher, collagenex, connetics corporation, dermik laboratories, embil pharmaceuticals, exeltis, genentech, innocutis, innovail, johnson & johnson, leo, l’oreal, 3m, onset, orthoneutrogena, pediapharm, pharmaderm, serono, skinmedica, stiefel laboratories, sun pharma, taro, triax, ucb, valeant pharmaceuticals, and warner-chilcott. he has participated in advisory boards for aclaris, allergan, almirall, anacor, biogen-idec, colbar, celgene, cipher, connetics, eos, exeltis, ferndale laboratories, genentech, intendis, innocutis, isdin, johnson & johnson, merz, orthoneutrogena, promius, quinnova, skinmedica, stiefel laboratories, sun pharma, valeant, and warner-chilcott. he is an investigator for acambis, allergan, amgen, anacor, astellas, asubio, berlex, biolife, biopelle, boehringeringleheim, breckinridge pharma, celgene, centocor, cellceutix, coherus, collagenex, combinatrix, connetics corporation, coria, dermavant, dermira, dow pharmaceutical sciences, dusa, eli lilly, exeltis, ferdale laboratories, foamix, genentech, glaxosmithkline, health point, idera, intendis, johnson & johnson, leo, l’oreal, 3m, maruho, merck, medicis, merz, novartis, noven, nucryst, obagi, onset, orthoneutrogena, promius, qlt, pharmaderm, pfizer, quinnova, quatrix, skinmedica, stiefel, sun pharma, tolerrx, ucb, valeant, warner-chilcott, and xenoport. he is a consultant for allergan, almirall, amgen, anacor, colbar, cipher, collagenex, connetics, exeltis, genentech, intendis, isdin, johnson & johnson, laboratory skin care, leo, medical international technologies, merck, merz, novartis, orthoneutrogena, promius, puracap, skinmedica, stiefel, sun pharma, taro, ucb, valeant, and zage. dr. knuckles is a speaker for siliq, cosentyx, otezla, eucrisa, ilumya, cimzia, sunpharma, novartis, celgene, abbvie, duobrii, bryhali, dupixent, enbrel, amgen, abbvie, humira, skyrizi. she is on advisory boards for promius, siliq, ortho dermatologics, corrona investigator, castle bioscience, novartis, sanofi-regeneron, and ilumya. dr. lebwohl is an employee of mount sinai and receives research funds from: abbvie, amgen, arcutis, astrazeneca, boehringer ingelheim, celgene, clinuvel, eli lilly, incyte, janssen research & development, llc, kadmon corp., llc, leo pharmaceutucals, medimmune, novartis, ortho dermatologics, pfizer, sciderm, ucb, inc., and vidac, and is also a consultant for allergan, almirall, arcutis, inc., avotres therapeutics, birchbiomed inc., boehringer-ingelheim, bristol-myers squibb, cara therapeutics, castle biosciences, corrona, dermavant sciences, evelo, foundation for research and education in dermatology, inozyme pharma, leo pharma, meiji seika pharma, menlo, mitsubishi, neuroderm, pfizer, promius/dr. reddy’s laboratories, theravance, and verrica. dr. litchman has no relevant conflicts of interest. dr. murina is a speaker for abbvie, celgene, eli lilly and company, janssen, and novartis. ryan rivera-oyola has no relevant conflicts of interest. dr. weinberg is a speaker for orthodermatologic. dr. wu is an investigator for abbvie, amgen, eli lilly, janssen, novartis; a consultant for abbvie, almirall, amgen, bristol-myers squibb, celgene, dermira, dr. reddy's laboratories, eli lilly, janssen, leo pharma, novartis, promius pharma, regeneron, sun pharmaceutical, and ucb, valeant pharmaceuticals north america llc; and a speaker for abbvie, celgene, novartis, regeneron, sanofi genzyme, sun pharmaceutical, ucb, valeant pharmaceuticals north america llc. dr. koo is a speaker and advisor for abbvie, amgen, celgene, janssen, eli-lilly, leo pharma, novartis, pfizer, strata skin science, sun pharma, and orthodermatologic. skin november 2019 volume 3 issue 6 copyright 2019 the national society for cutaneous medicine 373 funding: none corresponding author: quinn thibodeaux, md department of dermatology, ucsf 515 spruce street san francisco, ca, 94118, usa tel: (415) 476-4019 email: quinn.thibodeaux@ucsf.edu references: 1. wu jj, feldman sr, koo j, marangell lb. 2018. epidemiology of mental health comorbidity in psoriasis. j dermatolog treat. 29(5):487-495. 2. koo j, marangell lb, nakamura m, armstrong a, jeon c, bhutani t, wu jj. 2017. depression and suicidality in psoriasis: review of the literature including the cytokine theory of depression. j eur acad dermatol venereol. 31(12):1999-2009. 3. ortho dermatologics. siliqtm [package insert] u.s. food and drug administration website. fda.gov. revised [february, 2017]. accessed [august 11, 2019]. 4. lebwohl mg, papp ka, marangell lb, koo j, blauvelt a, gooderham m, wu jj, rastogi s, harris s, pillai r et al. 2018. psychiatric adverse events during treatment with brodalumab: analysis of psoriasis clinical trials. j am acad dermatol. 78(1):81-89.e85. 5. rusta-sallehy s, gooderham m, papp k. 2018. brodalumab: a review of safety. skin therapy lett. 23(2):1-3. 6. papp ka, reich k, paul c, blauvelt a, baran w, bolduc c, toth d, langley rg, cather j, gottlieb ab et al. 2016. a prospective phase iii, randomized, double-blind, placebo-controlled study of brodalumab in patients with moderate-tosevere plaque psoriasis. br j dermatol. 175(2):273-286. 7. pardridge wm. 2005. the blood-brain barrier: bottleneck in brain drug development. neurorx. 2(1):3-14. 8. gananca l, oquendo ma, tyrka ar, cisnerostrujillo s, mann jj, sublette me. 2016. the role of cytokines in the pathophysiology of suicidal behavior. psychoneuroendocrinology. 63:296310. 9. gooderham m, gavino-velasco j, clifford c, macpherson a, krasnoshtein f, papp k. 2016. a review of psoriasis, therapies, and suicide. j cutan med surg. 20(4):293-303. 10. pavelka k, chon y, newmark r, lin sl, baumgartner s, erondu n. 2015. a study to evaluate the safety, tolerability, and efficacy of brodalumab in subjects with rheumatoid arthritis and an inadequate response to methotrexate. j rheumatol. 42(6):912-919. 11. targan sr, feagan b, vermeire s, panaccione r, melmed gy, landers c, li d, russell c, newmark r, zhang n et al. 2016. a randomized, double-blind, placebo-controlled phase 2 study of brodalumab in patients with moderate-to-severe crohn's disease. am j gastroenterol. 111(11):1599-1607. 12. kaushik sb, lebwohl mg. 2019. psoriasis: which therapy for which patient: focus on special populations and chronic infections. j am acad dermatol. 80(1):43-53. 13. kaushik sb, lebwohl mg. 2019. psoriasis: which therapy for which patient: psoriasis comorbidities and preferred systemic agents. j am acad dermatol. 80(1):27-40. mailto:quinn.thibodeaux@ucsf.edu tapinarof cream 1% once daily for plaque psoriasis: improvements in quality of life and clinical efficacy in two pivotal phase 3 trials linda stein gold,1 christopher e. m. griffiths,2 anna m. tallman,3 philip m. brown,3 mark g. lebwohl4 1henry ford health system, detroit, mi, usa; 2dermatology centre, university of manchester, nihr manchester biomedical research centre, manchester, uk; 3dermavant sciences, inc., morrisville, nc, usa; 4icahn school of medicine at mount sinai, new york, ny, usa introduction ■ psoriasis is a chronic, immune-mediated disease that substantially impacts quality of life (qol) through itching, pain, and disfigurement1 ■ in addition to clinician-assessed efficacy endpoints, such as the physician global assessment (pga) and the psoriasis area and severity index (pasi), the importance of evaluating patient-reported outcomes (pros) is increasingly recognized – more than 70% of patients have reported that psoriasis had a moderate to extremely high impact on their daily life2 – discordance between pros and clinician-assessed outcomes has been observed for psoriasis3,4 ■ tapinarof (vtama®; dermavant sciences, inc., usa) is a first-in-class, non-steroidal, topical, aryl hydrocarbon receptor agonist approved by the food and drug administration for the treatment of plaque psoriasis in adults, and under investigation for the treatment of psoriasis in children down to 2 years of age and for atopic dermatitis in adults and children down to 2 years of age5 ■ tapinarof cream 1% once daily (qd) demonstrated highly statistically significant efficacy versus vehicle and was well tolerated in adults with mild to severe plaque psoriasis in two identical, 12-week, pivotal phase 3 trials, psoaring 1 (nct03956355) and psoaring 2 (nct03983980)6 ■ consistent with clinical efficacy as assessed by clinicians, tapinarof cream 1% qd demonstrated rapid, clinically meaningful, and highly statistically significant improvements in pros compared with vehicle in psoaring 1 and 2, including change in dermatology life quality index (dlqi) score from baseline to week 127 objective ■ to present further analyses of patient-reported and clinician-assessed outcomes for tapinarof cream 1% qd based on the dlqi, pga, and pasi in psoaring 1 and psoaring 2 materials and methods trial design ■ psoaring 1 and psoaring 2 were two identically designed, phase 3, multicenter (us and canada), double-blind, vehicle-controlled, randomized trials in which patients with mild to severe plaque psoriasis were randomized to tapinarof cream 1% qd or vehicle qd for 12 weeks (figure 1) figure 1. psoaring 1 and psoaring 2 trial design *patients with pga=2 (mild) and pga= 4 (severe) were limited to ~10% each of the total randomized population; with ~80% of the total randomized population having a pga=3 (moderate). bsa, body surface area; pga, physician global assessment; qd, once daily; r, randomized. endpoints and statistical analysis ■ the dlqi is a validated, dermatology-specific, 10-item patient questionnaire – each item rates impact of disease on qol on a 4-point scale from 0 (not at all) to 3 (very much) – total scores range from 0 to 30, with lower scores indicating better health-related qol (i.e., a lower impact of disease on qol) – a total dlqi score of 0 or 1 indicates “no effect at all” of disease on qol – a total dlqi score of 2–5 indicates a small effect, 6–10 a moderate effect, and >10 a very large effect on qol8 ■ efficacy assessments included pga and pasi ■ spearman rank correlations were used to evaluate relationships between changes from baseline in efficacy (assessed using pga and pasi) and changes from baseline in dlqi score at week 12 ■ analyses used observed cases and were based on the intention-to-treat population ■ for the proportion of patients with dlqi of 0 or 1, p values for differences between tapinarof cream 1% qd and vehicle were calculated using cochranmantel-haenszel analyses and stratified by baseline pga score. for the change in dlqi from baseline, p values were calculated using an analysis of covariance model with effects for treatment, baseline pga score, and baseline dlqi results baseline patient disease characteristics ■ the analyses included 683 tapinarof-treated patients and 342 vehicle-treated patients (table 1) ■ at baseline, 79.2%–83.9% of patients had a pga score of 3 (moderate), and mean pasi was 8.9–9.1 in psoaring 1 and 2, respectively ■ mean dlqi score was 8.2–8.7 across treatment groups and trials – only 5.6%–7.6% of patients had a dlqi of 0 or 1, indicating no impact of disease on qol table 1. baseline demographics and disease characteristics in psoaring 1 and psoaring 2 psoaring 1 psoaring 2 tapinarof cream 1% qd (n=340) vehicle qd (n=170) tapinarof cream 1% qd (n=343) vehicle qd (n=172) age, years, mean (sd) 49.8 (13.7) 49.1 (13.3) 50.0 (13.1) 50.0 (13.7) male, n (%) 213 (62.6) 86 (50.6) 188 (54.8) 102 (59.3) weight, kg, mean (sd) 91.7 (24.6) 92.8 (22.7) 92.9 (24.3) 89.6 (19.9) bmi, kg/m2, mean (sd) 31.4 (7.8) 32.5 (7.6) 31.8 (7.7) 30.7 (6.3) pga, n (%) 2 – mild 39 (11.5) 21 (12.4) 28 (8.2) 15 (8.7) 3 – moderate 271 (79.7) 133 (78.2) 288 (84.0) 144 (83.7) 4 – severe 30 (8.8) 16 (9.4) 27 (7.9) 13 (7.6) pasi, mean (sd) 8.7 (4.0) 9.2 (4.4) 9.1 (3.7) 9.3 (4.0) bsa affected, %, mean (sd) 7.8 (4.6) 8.2 (5.1) 7.8 (4.4) 7.3 (4.1) dlqi, mean (sd)* 8.2 (5.8) 8.7 (5.9) 8.5 (5.9) 8.6 (5.9) dlqi of 0 or 1, n (%)* 25 (7.4) 13 (7.6) 19 (5.6) 10 (5.8) *baseline dlqi data was missing for three patients in the tapinarof groups (two in psoaring 1; one in psoaring 2). bmi, body mass index; bsa, body surface area; dlqi, dermatology life quality index; pasi, psoriasis area and severity index; pga, physician global assessment; qd, once daily; sd, standard deviation. change in dlqi from baseline to week 12 ■ significant improvements in mean dlqi were achieved by week 4, the earliest evaluation time point; improvement continued through week 12 in the tapinarof cream 1% qd versus vehicle groups in psoaring 1 and 2: –5.0 vs –3.0 and –4.7 vs –1.6 (both p<0.0001), respectively (figure 2) figure 2. change in dlqi at week 4 and week 12 itt population, oc. least squares mean (se). dlqi, dermatology life quality index; itt, intention-to-treat; oc, observed cases; qd, once daily; se, standard error. correlation between dlqi and pga or pasi ■ improvements from baseline in dlqi and pga at week 12 in the tapinarof cream groups were statistically positively correlated in both psoaring 1 and 2 (spearman correlation: 0.28 and 0.29 [both p<0.0001]), respectively ■ improvements from baseline in dlqi and pasi at week 12 in the tapinarof cream groups were also statistically positively correlated in both psoaring 1 and 2 (spearman correlation: 0.28 and 0.40 [both p<0.0001]), respectively proportion of patients with dlqi of 0 or 1 ■ the proportion of patients achieving a dlqi of 0 or 1, indicating no effect of psoriasis on qol, was significantly higher in the tapinarof cream versus vehicle groups at week 12 in psoaring 1 and 2: 47.4% vs 23.3% and 44.9% vs 16.1% (both p<0.0001), respectively (figure 3) ■ statistically significant improvements in the proportion of patients achieving a dlqi of 0 or 1 with tapinarof cream versus vehicle were observed as early as week 4 in both trials figure 3. proportion of patients with dlqi of 0 or 1 itt population, oc. dlqi, dermatology life quality index; itt, intention-to-treat; oc, observed cases; qd, once daily. ■ figure 4 shows a patient treated with tapinarof cream 1% qd monotherapy who achieved dlqi=1 by week 4, and showed further improvement to dlqi=0 at week 12, as well as achieving the trial primary and secondary endpoints figure 4. improvement in dlqi, pasi, and pga in a patient with plaque psoriasis treated with tapinarof cream 1% qd pga and pasi are global efficacy assessments. example of one representative target lesion of one tapinarof-treated patient from the psoaring 1 clinical trial. individual results may vary. dlqi, dermatology life quality index; pasi, psoriasis area and severity index; pga, physician global assessment. conclusions ■ tapinarof cream 1% qd demonstrated rapid, clinically meaningful, and statistically significant improvements in investigator-assessed objective efficacy measures and patient-reported qol ■ in addition to overall improvement in total dlqi, a large proportion (45%–47%) of patients treated with tapinarof achieved a dlqi of 0 or 1 (no negative effects of psoriasis on their qol) by week 12, with a significant improvement observed as early as week 4 ■ agreement between investigator assessments of efficacy and patient-reported qol with tapinarof cream 1% qd provides additional confirmation of the clinically meaningful improvements in psoriasis demonstrated across these trials4 ■ the correlations between improvements in dlqi and investigator-assessed efficacy suggest that, beyond clinical improvements captured by the pga and pasi, other important factors, such as mental/emotional well-being and satisfaction with treatment, may contribute to the considerable qol improvements observed references 1. feldman sr, et al. am health drug benefits. 2016;9:504. 2. feldman sr, et al. cutis. 2013;92:258–263. 3. carr e, et al. jama dermatol. 2021;157:413–420. 4. griffiths c, et al. j eur acad dermatol venereol. 2018;32:1523–1529. 5. dermavant sciences. vtama (tapinarof) cream, 1%: us prescribing information. 2022. https://www.vtama. com/docs/dmvt_vtama_pi.pdf. accessed 22 july 2022. 6. lebwohl mg, et al. n engl j med. 2021;385(24):2219–2229. 7. bissonnette r, et al. poster presented at: american academy of dermatology; march 19-23, 2021. 8. hongbo y, et al. j invest derm. 2005;125:659–664. acknowledgments this trial was funded by dermavant sciences, inc. the authors thank the participating investigators, patients and their families, and colleagues involved in the conduct of the trial. l.s.g. has served as a consultant, and/or has received payment for the development of educational presentations, and/or has received grants from arcutis, amgen, bristol myers squibb, dermavant sciences, inc., eli lilly, leo pharma, ortho dermatologic, and ucb biopharma. c.e.m.g. has received honoraria and/or research grants from almirall, amgen, bristol myers squibb, boehringer-ingelheim, dermavant sciences, inc., eli lilly, gsk, janssen, novartis, ono pharmaceutical, and ucb pharma. a.m.t. and p.m.b. are employees of dermavant sciences, inc., with stock options. m.g.l. has received grants, and/or is a consultant for abbvie, amgen, aditum bio, almirall, altrubio inc., anaptysbio, arcutis, aristea therapeutics, arrive technologies, avotres, biomx, boehringer ingelheim, bristol myers squibb, cara therapeutics, castle biosciences, corrona, dermavant sciences, inc., dr. reddy’s laboratories, eli lilly, evelo biosciences, evommune, inc., facilitation of international dermatology education, forte biosciences, foundation for research and education in dermatology, helsinn therapeutics, hexima ltd, incyte, janssen research & development, leo pharma, llc, meiji seika pharma, mindera, ortho dermatologics, pfizer, regeneron, seanergy, ucb biopharma, inc., and verrica. editorial and medical writing support under the guidance of the authors was provided by apothecom, uk, and was funded by dermavant sciences, inc. in accordance with good publication practice (gpp3) guidelines (ann intern med. 2015;163:461–464). contact dr linda stein gold at lstein1@hfhs.org with questions or comments. adults with mild to severe plaque psoriasis • aged 18–75 years old • pga score ≥2* • bsa ≥3% to ≤20% double-blind treatment (12 weeks) 2:1 2:1 tapinarof 1% qd (n=340) tapinarof 1% qd (n=343) vehicle qd (n=170) vehicle qd (n=172) (n=510) (n=515) r r tapinarof cream 1% qd vehicle qd –3.8 –5.0 –3.8 –4.7 –2.0 –3.0 –1.1 –1.6 -8 -6 -4 -2 0 c h an g e in d lq i week 12week 4 week 4week 12 δ –3.1 p<0.0001 δ –2.7 p<0.0001 δ –2.0 p<0.0001 δ –1.7 p<0.0001 31.2 47.4 27.6 44.9 15.2 23.3 16.0 16.1 0 20 10 50 40 30 60 80 70 p ro p o rt io n o f p at ie n ts , % week 12week 4 week 4week 12 p=0.0002 p<0.0001 p=0.0038 p<0.0001 tapinarof cream 1% qd vehicle qd • dlqi=9 • pasi=16.0 • pga=3 • dlqi=1 • pasi=5.5 • pga=2 • dlqi=0 • pasi=2.4 • pga=1 baseline week 4 week 12 skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 295 original research margin status predicts outcome in patients with cutaneous squamous cell carcinoma of the scalp: the westmead hospital experience rajith l. mendis mbbs,1 gary morgan mbbs,1,2 muzib abdul-razak mch, mbbs,1,2 eva wong mbbs(hons),1,2 julie howle mbbs, ms,1,2 val gebski mstat,2,3 michael veness md2,4 1 head and neck surgery, westmead hospital, westmead, nsw 2 sydney medical school, university of sydney, sydney, nsw 3 nhmrc clinical trials centre, the university of sydney, sydney, nsw 4 department of radiation oncology, westmead hospital, westmead, nsw non melanoma skin cancer (nmsc) comprising basal cell carcinoma (bcc) and cutaneous squamous cell carcinoma (cscc) is the most common malignancy in australia with a rising incidence.1 while most are cured by excision alone, there is a subset of patients with cscc who develop locoregional recurrence.2 pathological risk factors for recurrence in the setting of cscc include: margin status, tumor thickness, invasion beyond subcutaneous fat, the presence of perineural invasion (pni), diameter >20mm and poor differentiation3 in addition to immunosuppression and recurrent tumors.4 the relevance of margin status in cscc both in terms of treatment recommendations and patient outcome remains unclear with limited high-level evidence. as such, clinicians are abstract background: an involved or close resection margin in the setting of cutaneous scc (cscc) is associated with the risk of developing recurrence. the scalp poses unique anatomical challenges when obtaining adequate resection margins and further treatment may be required. we aimed to investigate the risk of recurrence in patients with scalp csccs and the role of adjuvant radiotherapy. methods: eligible patients with cscc of the scalp treated with curative intent at westmead hospital, sydney, were identified and patient, tumor and treatment factors analyzed. patients were categorized based on margin status and analyzed in terms of treatment delivered, local recurrence and survival. results: in total, 114 patients with a median age of 70 years with the majority (81%) male, were identified with a median follow up of 5.6 years. following surgery, 52 patients (46%) had clear margins, 62 (54%) had close (≤2mm) or involved margins, with a significant difference in the 5 -year disease specific mortality of 20% and 35%, respectively (p=0.05). twenty-eight patients (25%) underwent surgery and adjuvant radiotherapy, most with a close/involved margin. there was no significant difference in the risk of developing local recurrence between the group of patients in whom a clear margin was obtained and the group in whom the margin was close/involved (p=0.23). conclusion: margin status had a significant impact on disease specific mortality, but was not associated with the risk of developing local recurrence. the addition of adjuvant radiotherapy in select high-risk patients may improve outcome although this was not demonstrated in our study. introduction skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 296 reliant on the results of lower-level institutional observational cohort studies and underlying oncological principles. margin status (clear vs involved) has been shown to have an impact on survival,4 and this benefit persists when comparing outcomes by margin status in patients undergoing adjuvant radiotherapy.5 in light of emerging evidence, incomplete excision has been proposed as an additional high-risk feature for a poor outcome in a review article assessing the different definitions of high-risk features and the evidence supporting these.6 the incidence of incomplete excisions of cscc is reported as between 7.6-9.4% across a range of clinical settings7,8 and in the majority of cases (up to 78%) the deep excision margin is involved, suggesting that using wider peripheral resection margins may be of limited benefit.8,9 a close or positive margin following resection of cscc is associated with a recurrence risk of up to 37%,10 and further treatment is often recommended, which may involve a wider more complex resection or local adjuvant radiotherapy. managing patients with cscc of the scalp poses site specific issues in terms of anatomical restrictions limiting further resection, pathologically aggressive behavior of the tumor, and the potential of adjuvant scalp radiotherapy associated with skin graft loss and osteoradionecrosis of the underlying skull in occasional patients.11 the relatively thin soft tissue components have implications for obtaining a negative deep margin, which may require removal of periosteum or the outer table of the skull.9 there are limited data documenting outcomes of patients with scalp csccs with close or involved margins following surgical resection. we aimed to analyze our institution’s outcomes for patients treated with cscc of the scalp in order to investigate the association of margin status with the patient outcomes and to analyze the effect of treatment options on the risk of developing local recurrence and on disease specific mortality. patients with a primary scalp cscc with documented margin status were identified from a prospectively maintained computer database of patients diagnosed with metastatic cscc to parotid and/or cervical lymph nodes. relevant demographic data and the characteristics of the primary tumor were recorded including tumor grade, pni, lymphovascular invasion (lvi) and treatment details. many patients had initial scalp treatment elsewhere and were referred to our service after developing locoregional recurrence. follow up data including disease related outcomes and status at last review were recorded with follow up calculated from the completion of treatment of the scalp primary. statistical analysis margin status was categorized into two patient groups: a high-risk group (hrg) comprising patients with an involved or close margin (≤2mm); a low-risk group (lrg) having a clear margin (>2mm). these two groups were compared in terms of treatment delivered, risk of local recurrence (lr), and disease specific mortality, with multivariate analysis performed to identify prognostic factors for both lr and disease specific mortality. methods incorporating competing risks were used in the analysis of lr, and disease specific mortality.12,13 methods skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 297 this study was conducted with approval from the western sydney local health district’s human research ethics committee. a total of 114 patients met the inclusion criteria with a median age of 70 years (range 34-91), most were male (81%), and the median follow up was 5.6 years. the majority of cscc were moderately (n=42, 37%) or poorly (n=45, 40%) differentiated (table 1). fifty-four patients (47%) had primary cscc ≥2cm, and tumor size data was missing in 19. a total of 52 patients (46%) had clear excision margins (lrg) and 62 (54%) had close (≤2mm) or involved margins (hrg). a total of 28 patients (25%) were treated with surgery and adjuvant radiotherapy with most 24/28 (85%) from the hrg (figure 1). the majority of patients in the lrg (92%) were treated with surgery alone. figure 1. flow diagram of treatment (surgery +/ adjuvant radiotherapy) and local recurrence rates by margin status (low risk group (lrg): >2mm; high risk group (hrg): ≤2mm) within our cohort 23 patients (20%) experienced local recurrence. there was no significant difference in lr rates between the lrg (8 patients, 15%) and hrg (15 patients, 24%), (p= 0.23, see figure 2). multivariate analysis was performed including patient factors (age, sex, immunosuppression, treatment) and tumor factors (grade, pni, vascular invasion, margin status) and there were no significant factors that predicted for lr including margin status or the addition of adjuvant radiotherapy. within the hrg, the lr rate for those undergoing surgery alone was 29% (11/38) compared with 17% (4/24) for those treated with surgery and adjuvant radiotherapy (table 2); as the difference in the lr rate between the lrg and hrg was not significant, testing within the subgroups was not performed. figure 2. local recurrence by margin status (low risk group (lrg): >2mm; high risk group (hrg): ≤2mm) the 5 year disease specific mortality (figure 3) was 20% in the lrg compared to 35% in the hrg (p=0.05), and on multivariate analysis no additional significant factors impacting on disease specific mortality were identified. results skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 298 figure 3. disease specific mortality by margin status (low risk group (lrg): >2mm; high risk group (hrg): ≤2mm) the optimal management of patients with inadequately excised cscc of the scalp is unclear as is an accepted definition of an adequate excision margin, with variability within global guidelines, ranging from 4mm to 10mm, and based on primary tumor risk derived from tumor size, thickness, differentiation and subsite.14,15 in a systematic review of 21,569 cases of cscc, the overall incidence of incomplete excisions was only 9.4% ,8 and a series of 633 csccs managed across four regional plastic surgery departments documented an incidence of involved margins of 15% with an overall recurrence rate of 6.7% at 5 years, the majority (96%) occurring within 2 years.7 in comparison, in our study, over half of the patients (54%) had tumors excised with close/involved margins, which may reflect the high risk nature of the cscc in the study population and our arbitrary definition of a close margin as 2mm. using wider peripheral resection margins may not reduce the proportion of incomplete excisions as often the deep margin is primarily involved8, with a scalp specific retrospective review documenting deep margin failure in 32 of 41 cases (78%) with involved margins.9 most of our patients were older males, many with an extensive history of nmsc treated over the years. we consider cscc of the scalp a high-risk cutaneous sub-site, comparable to the lower lip and external ear in terms of risk of developing parotid/cervical nodal metastases,16 and as such they represent ~10% of cases with metastatic nodal disease in our own previously published data.17 unlike in bcc where a patient with a close or involved margin is at risk of local relapse and observation with expectant treatment (i.e. radiotherapy or surgery) is an accepted option in many, further treatment is generally recommended for an involved or close cscc margin due to the increased risk of developing local recurrence which in turn increases the risk of subsequent nodal metastases.10 many patients developing local recurrence of scalp cscc are not always candidates for surgical salvage. anatomical restrictions of the scalp need to be carefully considered as further resection of an involved or close deep margin may necessitate either more complex reconstruction or even skull resection, and adjuvant radiotherapy can be associated with risks including late graft loss with subsequent bone exposure, as well as osteoradionecrosis of the skull.11 discussion skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 299 table 1. patient characteristics lrg † hrg ‡ total gender male 43 (46.7%) 49 (53.3%) 92 female 9 (40.9%) 13 (59.1%) 22 immunosuppression yes 5 (45.5%) 6 (54.5%) 11 no 47 (45.6%) 56 (54.4%) 103 grade well differentiated 7 (46.7%) 8 (53.3%) 15 moderately differentiated 20 (47.6%) 22 (52.4%) 42 poorly/undifferentiated 20 (43.5%) 26 (56.5%) 46 unknown 4 (40%) 6 (60%) 10 perineural invasion yes 4 (16.7%) 20 (83.3%) 24 no 17 (42.5%) 23 (57.5%) 40 unknown 31 (62%) 19 (38%) 50 vascular invasion yes 0 7 (100%) 7 no 24 (46.2%) 28 (53.8%) 52 unknown 28 (50.9%) 27 (49.1%) 55 † low risk group (lrg): >2mm ‡ high risk group (hrg): ≤2mm table 2. patterns of recurrence (following treatment of nodal disease) no recurrence local regional or distant total lrg† 35 (67%) 8 (15%) 9 (17%) 52 hrg‡, surgery alone 12 (32%) 11 (29%) 15 (40%) 38 hrg‡, surgery + adjuvant radiotherapy 9 (38%) 4 (17%) 11 (46%) 24 † low risk group (lrg): >2mm ‡ high risk group (hrg): ≤2mm skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 300 in a review of 235 patients treated for cscc of the scalp at the peter maccallum cancer centre, melbourne, an incomplete excision rate of 24% was reported. in total, 22 patients (9%) experienced local recurrence with margin status reported in 11/22, with 4 involved. of note most that recurred (16/22) did not receive adjuvant radiotherapy.9 in a series of scalp csccs 60% (3/5) of patients with an involved pericranium margin experienced local recurrence, and of those with a close (≤2mm) deep margin 8% (3/37) experienced local recurrence.18 no patients received adjuvant radiotherapy and because of the low rate of local recurrence in patients with a close but clear deep margin the authors suggested that close observation may be appropriate. radiotherapy is an effective modality in both the definitive and adjuvant setting in patients with cscc and also in patients who are not optimal candidates for surgery (or more extensive re-excision surgery).19 a clear role and benefit of adjuvant radiotherapy for improving local control and survival in the setting of close or involved margins in cscc has not been well investigated and remains contentious. many patients are at competing risks of developing regional and distant relapse or an intervening co-morbid medical event and establishing a benefit can be difficult. in a series of 11 patients all with locally advanced csccs undergoing adjuvant radiotherapy for positive excision margins, but without gross residual disease, the majority (82%) had poor outcomes including 4 developing local recurrence, 7 developing nodal metastases and 2 with distant metastases.20 this study confirms the importance of aggressive surgical management to achieve negative margins whenever feasible and is consistent with our findings of a survival advantage for those with clear resection margins. a case matched study investigating patients with high risk cscc treated with surgery alone, compared to surgery and adjuvant radiotherapy, included patients with clear surgical margins and did not identify a significant difference in outcomes including local recurrence, distant metastases or disease specific survival. a sub-group analysis of 33 patients with large caliber pni (≥0.1mm), 16 treated with surgery and adjuvant radiotherapy and 17 treated with surgery alone, identified no significant difference in outcomes, although all 3 local recurrences occurred in patients undergoing surgery alone.2 within our study only 4 patients in the lrg underwent adjuvant radiotherapy so we were unable to draw any conclusions about the benefit of additional treatment in patients with clear margins. a recent meta-analysis reported that margin status, pni and immunosuppression were all factors associated with a significant reduction in os, and that adjuvant radiotherapy improved os.4 based on this limited published evidence, we suggest that margin status is relevant in making a decision regarding adjuvant radiotherapy. in our study, having a close/positive margin was associated with an increasing risk of developing lr (24 vs 15%) and the addition of adjuvant radiotherapy showed a trend towards improved outcomes for this hrg (lr of 17% vs 29% for surgery alone). we found that margin status had a significant effect on disease specific mortality with a survival benefit for those in the lrg and postulate that an involved margin may be an indicator of aggressive, infiltrative tumor biology and associated with worse outcomes. we acknowledge the weaknesses of our study which include its retrospective methodology, although the analyzed computer database has been prospectively maintained by the senior author for over 20 skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 301 years. there is also selection bias as all patients had been referred to a major teaching hospital with metastatic cscc to the parotid and/or cervical lymph nodes, thus the primary tumors in our patient population were high-risk, which may account for the high number in the hrg. as most (80-85%) developed metastatic lymph nodes following scalp treatment (12-24 months) we don’t believe this detracts from the issues regarding the management and outcome of the scalp cscc. margin status had a significant impact on disease specific mortality, but did not appear to be associated with the risk of developing local recurrence. the addition of adjuvant radiotherapy in select high-risk patients may improve outcome although this was not demonstrated in our study. conflict of interest disclosures: none funding: none corresponding author: rajith mendis, mbbs department of head and neck surgery westmead hospital, westmead, nsw 2145 email: rajith.mendis@health.nsw.gov.au references: 1. perera e, gnaneswaran n, staines c, win ak, sinclair r. incidence and prevalence of nonmelanoma skin cancer in australia: a systematic review. australas j dermatol 2015; 56: 258–267. 2. ruiz es, koyfman sa, que skt, kass j, schmults cd. evaluation of the utility of localized adjuvant radiation for node-negative primary cutaneous squamous cell carcinoma with clear histologic margins. j am acad dermatol 2020; 82: 420–429. 3. thompson ak, kelley bf, prokop lj, murad mh, baum cl. risk factors for cutaneous squamous cell carcinoma recurrence,metastasis, and disease-specific death: a systematic review and meta-analysis. jama dermatology 2016; 152: 419–428. 4. zhang j, wang y, wijaya wa, liang z, chen j. efficacy and prognostic factors of adjuvant radiotherapy for cutaneous squamous cell carcinoma: a systematic review and metaanalysis. j eur acad dermatology venereol 2021. doi:10.1111/jdv.17330. 5. newman jg, hall ma, kurley sj et al. adjuvant therapy for high-risk cutaneous squamous cell carcinoma: a 10-year review. head neck 2021; : 1–22. 6. skulsky sl, o’sullivan b, mcardle o et al. review of high‐risk features of cutaneous squamous cell carcinoma and discrepancies between the american joint committee on cancer and nccn clinical practice guidelines in oncology. head neck 2017; 39: 578–594. 7. khan k, mykula r, kerstein r et al. a 5-year follow-up study of 633 cutaneous scc excisions: rates of local recurrence and lymph node metastasis. j plast reconstr aesthetic surg 2018; 71: 1153–1158. 8. nolan gs, kiely al, totty jp et al. incomplete surgical excision of keratinocyte skin cancers: a systematic review and meta-analysis. br j dermatol 2021 jun;184(6):1033-10442021 doi:10.1111/bjd.19660. 9. estall v, allen a, webb a, bressel m, mccormack c, spillane j. outcomes following management of squamous cell carcinoma of the scalp: a retrospective series of 235 patients treated at the peter maccallum cancer centre. australas j dermatol 2017; 58: e207–e215. 10. caparrotti f, troussier i, ali a, zilli t. localized non-melanoma skin cancer: risk factors of post-surgical relapse and role of postoperative radiotherapy. curr treat options oncol 2020; 21. doi:10.1007/s11864020-00792-2. 11. lang pg, braun ma, kwatra r. aggressive squamous carcinomas of the scalp. dermatologic surg 2006; 32: 1163–1170. 12. gray rj. a class of k-sample tests for comparing the cumulative incidence of a competing risk. ann stat 1988; : 1141–1154. 13. fine jp, gray rj. a proportional hazards model for the subdistribution of a competing risk. j am stat assoc 1999; 94: 496–509. 14. nahhas af, scarbrough ca, trotter s. a review of the global guidelines on surgical margins for nonmelanoma skin cancers. j clin aesthet dermatol 2017; 10: 37. 15. kiely j, kostusiak m, bloom o, roshan a. poorly differentiated cutaneous squamous cell carcinomas have high incomplete excision conclusion skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 302 rates with uk minimum recommended predetermined surgical margins. j plast reconstr aesthetic surg 2020; 73: 43–52. 16. mo j, miller cj, karakousis g, keele l, cohen j, krouse rs. the scalp is a high-risk site for cutaneous squamous cell carcinoma metastasis. j am acad dermatol 2021; 84: 1742–1744. 17. howle jr, morgan gj, kalnins i, palme ce, veness mj. metastatic cutaneous squamous cell carcinoma of the scalp. anz j surg 2008; 78: 449–453. 18. jenkins g, smith ab, kanatas an, houghton dr, telfer mr. anatomical restrictions in the surgical excision of scalp squamous cell carcinomas: does this affect local recurrence and regional nodal metastases? int j oral maxillofac surg 2014; 43: 142–146. 19. haehl e, rühle a, klink r et al. the value of primary and adjuvant radiotherapy for cutaneous squamous cell carcinomas of the head-and-neck region in the elderly. radiat oncol 2021; 16: 1–13. 20. ruiz es, koyfman sa, kass j, schmults cd. surgery and salvage limited-field irradiation for control of cutaneous squamous cell carcinoma with microscopic residual disease. jama dermatology 2019; 155: 1193–1195. skin july 2022 volume 6 issue 4 (c) 2022 the authors. published by the national society for cutaneous medicine. 303 powerpoint presentation • treatment convenience of cal/bdp cream, measured by the psoriasis treatment convenience scale (ptcs)1 at week 8, was demonstrated to be significantly better than cal/bdp ts on all individual item questions including overall satisfaction (question 6) (table 2). • overall, safety assessments during the trial demonstrated that cal/bdp cream was well-tolerated. • baseline characteristics of patients with moderate psoriasis included in this subgroup analysis are presented in table 1. • the pga treatment success in patients with moderate psoriasis was significantly greater for cal/bdp cream (45.3%) than for cal/bdp ts (27.5%) at week 8 (p<0.0001) with significant difference also at week 4 (figure 1a). • noticeable difference (≥ 1 grade improvement in pga) was seen as early as week 1 in the cal/bdp cream group (38.2% of patients1). at week 8, this increased to 88.4% of patients in the cal/bdp cream group compared to 72.6% in the cal/bdp ts group (p<0.0001) (figure 1b). results linda stein gold1, johan selmer2, morten præstegaard2, april armstrong3 1dermatology clinical research, henry ford health system, detroit, michigan, usa ; 2mc2 therapeutics, hørsholm, denmark; 3keck school of medicine, department of dermatology, university of southern california los angeles, usa calcipotriene and betamethasone dipropionate cream demonstrates superior efficacy in moderate plaque psoriasis compared to topical suspension: a subgroup analysis of a phase 3 trial • calcipotriene and betamethasone dipropionate (50 microgram/g cal and 0.5 mg/g bdp) cream (cal/bdp cream) is based on padtm technology enabling development of an easy to apply, aqueous cream of cal and bdp, despite their known ph-related instability when combined in the presence of water. • the objective of this subgroup analysis is to present data from a phase 3 trial on the efficacy and convenience of cal/bdp cream in patients with moderate plaque psoriasis compared to cal/bdp topical suspension (ts). introduction • writing support was provided by anja snel-prentø. • the study was funded by mc2 therapeutics. acknowledgements conclusions • cal/bdp cream is an innovative topical treatment for plaque psoriasis based on pad™ technology. • cal/bdp cream showed significant improvement of pga treatment success, mpasi75, dlqi satisfaction and psoriasis treatment convenience compared to cal/bdp ts active comparator in patients with moderate plaque psoriasis. • the combination of high efficacy, favorable safety, and treatment convenience of cal/bdp cream may lead to improved adherence to therapy and thereby better treatment outcomes for patients with moderate psoriasis. methods • cal/bdp cream was evaluated in a phase 3, randomized, multicenter, investigator-blind, parallel-group trial comparing the efficacy and safety of cal/bdp cream to cal/bdp ts in adults with plaque psoriasis (nct03308799) . • the trial enrolled 796 patients at 55 clinical sites across the united states. patients were instructed to apply the trial medication topically once daily to affected areas of the body for up to 8 weeks. • at baseline, 641 patients with moderate psoriasis, based on physician global assessment (pga), score of 3, were included in the subgroup analysis. • the primary efficacy endpoint was the proportion of patients with treatment success at week 8, defined as minimum two-grade decrease from baseline in pga score to clear or almost clear disease (grade 0 or 1). • statistical analyses of the pga moderate patient subgroup were based on a modified intent-to-treat population (mitt). for pga, mpasi and dlqi a treatment policy strategy and multiple imputation for missing data were applied. for ptcs a while-on-treatment strategy and last observation carried forward for missing data were applied. categorial endpoints were evaluated by a logistic regression model and ptcs by an ancova model. table 1. baseline characteristics of patients with moderate psoriasis (pga=3) figure 1. pga success (a) and pga improvement (b) in patients with moderate psoriasis by weeks of treatment mpasi, modified pasi. dlqi, dermatology life quality index. ptcs, psoriasis treatment convenience scale, bdp, betamethasone dipropionate; cal, calcipotriene; ts, topical suspension. mitt, modified intent-to-treat population including all patients with at least one assessment after starting treatment. p-values represent comparison between cal/bdp cream and cal/bdp ts. 1based on observed cases. figure 2. mpasi75 (a) and dlqi satisfaction (b) in patients with moderate psoriasis by weeks of treatment • cal/bdp cream demonstrated significantly greater mpasi75 compared to cal/bdp ts in moderate psoriasis patients (42.3% versus 29.7%; p=0.0027) with significant difference also at week 4 (p=0.0008) (figure 2a). • 45.9% of patients treated with cal/bdp cream reported dlqi satisfaction at week 8 (score of 0 or 1, indicating no impact of psoriasis on quality of life) versus 31.2% in the cal/bdp ts group (p=0.0016) (figure 2b). 1feldman sr, præstegaard m, andreasen ah, selmer j, holm-larsen t. validation of the self-reported psoriasis treatment convenience scale (ptcs). dermatol ther (heidelb). 2021 dec;11(6):2077-2088. references table 2. ptcs scores for moderate psoriasis patients (cal/bdp cream vs. ts) # question odds ratio (ci 95%) p-value 1 how easy was the treatment to apply to the skin? 2.91 (1.33, 6.37) 0.0075 2 how greasy was the treatment when applying it to the skin? 9.89 (4.50, 18.07) <0.0001 3 how moisturized did your skin feel after applying the treatment? 3.44 (1.73, 6.84) 0.0004 4 how greasy did your skin feel after applying the treatment? 8.87 (4.44, 17.78) <0.0001 5 how much did treating your skin disrupt your daily routine? 3.82 (1.82, 8.00) 0.0004 6 overall, how satisfied were you with the medical treatment? 5.42 (2.64, 11.09) <0.0001 cal/bdp cream (n=271) cal/bdp ts (n=278) cream vehicle (n=92) mean bsa (sd) 7.9 (6.2) 9.0 (7.3) 8.3 (6.5) mean mpasi (sd) 8.0 (3.8) 8.3 (4.1) 7.9 (4.1) mean dlqi (sd) 9.6 (6.3) 10.6 (7.0) 9.1 (6.3) 29.9 45.3 14.6 27.5 2.7 6.1 0 10 20 30 40 50 60 week 4 week 8 % p g a t re a tm e n t s u c c e s s p<0.0001 p<0.0001 77.2 88.4 65.2 72.6 31.7 40.2 0 20 40 60 80 100 week 4 week 8 % p g a i m p ro v e m e n t p<0.0001p=0.0027 23.4 42.3 12.2 29.7 4.8 6.2 0 10 20 30 40 50 week 4 week 8 % m p a s i 7 5 p=0.0027 p=0.0008 35.0 45.9 28.6 31.2 13.1 17.5 0 10 20 30 40 50 60 week 4 week 8 % d l q i s a ti s fa c ti o n ( 0 o r 1 ) p=0.0016 a) b) a) b) cal/bdp cream cal/bdp ts cream vehicle cal/bdp cream cal/bdp ts cream vehicle figure 3. improvement of plaque psoriasis in a patient with moderate psoriasis baseline week 1 week 4 week 8week 6 pga treatment success pga improvement mpasi 75 dlqi satisfaction (score 0 or 1) pictures from mc2-01-c2 phase 3 trial; informed consent to publish pictures has been obtained from the patient. odds ratios indicate comparison in favor of cal/bdp cream to cal/bdp ts. dfd-01, a betamethasone dipropionate 0.05% spray, improved quality of life and treatment satisfaction in subjects with moderate psoriasis joseph fowler, md1; kent allenby, md2; srinivas sidgiddi, md2 1dermatology specialists research, louisville, ky; 2promius pharma, a subsidiary of dr. reddy’s laboratories, princeton, nj conclusions financial support: this study was funded and sponsored by the dr. reddy’s laboratories group of companies drl publication # 786 -1.1 -0.6 -1.2 -1 -0.8 -0.6 -0.4 -0.2 0 iga change baseline to day 14 bsa 3% to 10% bsa >10% -2.6 -2.8 -2.85 -2.8 -2.75 -2.7 -2.65 -2.6 -2.55 -2.5 tss change baseline to day 14 bsa 3% to 10% bsa > 10% 44.9 48.1 43 44 45 46 47 48 49 tsqm-ii scores at day 14 bsa 3% to 10% bsa > 10% -0.8 -2.5 -3 -2.5 -2 -1.5 -1 -0.5 0 % bsa change baseline to day 14 bsa 3% to 10% bsa > 10% change in clinical and qol parameters from baseline to day 14 (iit population) 1. finlay ay, khan gk. "the dermatology life quality index: a simple practical measure for routine clinical use". british association of dermatologists annual meeting, oxford, july 1993. british journal of dermatology, 1993;129(suppl 42):27. reference ¾ of 45 subjects enrolled, 24 had low bsa (3%-10%) and 21 had high bsa (>10%). ¾ 14 days of twice daily dfd-01 treatment was associated with decreased mean values of iga (-0.9), tss (-2.7), and bsa (-1.5%). ¾ mean iga reduction was greater in the low bsa group, whereas mean tss and bsa reductions were greater in the high bsa group. ¾ dlqi decreased from a mean of 8.9 ± 6.7 at baseline to 3.3 ± 3.6 at day 14. the high bsa group showed greater improvement in qol. ¾ mean tsqm-ii score was 46.2 at day 14, with greater treatment satisfaction in the high bsa group (48.1 vs 44.9). introduction ¾ dfd-01 [sernivo™ (betamethasone dipropionate) spray, 0.05%] is a spray formulation approved for the treatment of mild to moderate plaque psoriasis in adults. ¾ the efficacy and tolerability of dfd-01 have been demonstrated in subjects with extensive, moderate plaque psoriasis (10% to 20% body surface area [bsa]). ¾ this study assessed quality of life (qol) and treatment satisfaction ratings of subjects with moderate plaque psoriasis. ¾ dfd-01 was associated with decreased iga, tss, and bsa in adults with moderate plaque psoriasis. ¾ treatment was associated with improved qol after 2 weeks of treatment, and subjects reported satisfaction with dfd-01 in both low (3%-10%) and high (>10%) bsa groups. ¾ dfd-01 treatment resulted in better outcomes in subjects with higher bsa involvement at baseline. methods ¾ in this open-label, multicenter study, adults with moderate plaque psoriasis (iga = 3; bsa > 3%, excluding intertriginous areas) applied dfd-01 to affected areas twice daily for 28 days. for each subject, investigators identified 2 target lesions representative of overall disease. ¾ assessments occurred at days 1 (baseline), 8, 14, and 29. at each visit, disease severity was assessed by iga, total sign score (tss) of target lesions, and bsa, and target lesions were photographed. ¾ qol was evaluated using the dermatology life quality index (dlqi), a 10-item questionnaire assessing impact of skin disease on quality of life (scores range from 0 (best) to 30 (worst)1. ¾ patient satisfaction was evaluated using the treatment satisfaction questionnaire for medication–version ii (tsqm-ii), 9-items assessing effectiveness, side effects, convenience, and global satisfaction, yielding scores ranging from 0 (extremely unsatisfied) to 100 (extremely satisfied). ¾ primary endpoints were: (1) change from baseline in clinical response and qol at day 14 (2) treatment satisfaction at day 14 results change in clinical and qol parameters from baseline to day 14 (iit population) fc17posterpromiusfowlerdfdpsoriasis.pdf •lha is a sa derivative shown to be effective and tolerable in exfoliating the skin and promoting dermal thickening. the use of lipohydroxy acid in skin care and acne treatment •lipohydroxy acid (lha) is a salicylic acid (sa) derivative with skin renewing, exfoliating, and acne treating properties. •with a higher molecular weight than sa and an added fatty chain, it is more lipophilic than sa(1). •lha was first developed by l’oréal researchers in the 1980’s and is found only in l’oréal brand skin care products. joshua a zeichner, md icahn school of medicine at mount sinai, new york, ny introduction exfoliating/skin renewing properties conclusion oh o cooh lha or 2-hydroxy 5-octanoyl benzoic acid •little lha penetrates past the stratum corneum, with a large reservoir effect. in vitro data revealed only 6% of lha penetrated past the stratum corneum versus 58% of sa(1,2). tape-strip analysis revealed 17.1% of lha was retained in the stratum corneum after a 4 day application period, versus 9.7% of sa(1,3). •lha exhibits unique exfoliating properties. being highly lipophilic slows penetration and results in slow cell-by-cell corneocyte exfoliation thought to mimic physiologic desquamation(1). •lha has been shown to provide stratum corneum thinning (-19.8% at 4 weeks) vs control (0%), placebo (1.2%), salicylic acid (-3.7%) and tretinoin (-1.2%)(4). •lha has been shown to result in dermal thickening comparable to tretinoin thought to be due to stimulation of glycosaminoglycans, hyaluronic acid, collagen, and elastin(1,4). •studies in human skin demonstrate enhanced cell turnover, explained by signaling from lamellar lipids during desquamation or direct mechanical exfoliating forces. this is controversial(5,6). •being highly lipophilic nature, lha penetrates well into the pilosebaceous unit. •in a split-face study of patients with comedonal acne, follicular casts were reduced by 47% (p<0.01) and their size by 54% (p<0.01) compared to the untreated side, as evaluated by cyanoacrylate skin strips(7). •a 2 week study of 14 acne patients showed that twice daily lha application resulted in a significant decrease in size and number of comedones with approximately an 85% reduction in follicular plugs(8). data in treating acne •the fda otc acne monograph includes benzoyl peroxide (bpo), sa, and sulfur. •while not indicated for acne, data exist on the use of lha in treating acne. •study 1(9): •design: monotherapy lha vs bpo in acne patients. •efficacy: lha equal to bpo. •tolerability: lha more tolerable than bpo. •study 2(10): •design: •arm 1: otc fixed dose combination of 5.5% bpo/lha qam and rx tretinoin 0.025% cream qpm. •arm 2: rx fixed dose combination bpo 5%/clindamycin 1% gel qam and rx tretinoin 0.025% qpm. •patients randomized 1:1, with treatment for 12 weeks. •66 patients, ages 18-50 years, with mild-moderate acne. •efficacy: •equal efficacy between arms with similar reductions in comedonal, inflammatory, and total lesion counts at weeks 4, 8, and 12 and statistically better than baseline (p<0.05). •tolerability: •skin dryness and peeling at early time points in both arms. •at week 2, there was statistically less erythema for the bpo/lha arm vs bpo/cp arm (p=0.042). •no other differences in tolerability between treatment arms. •lha has comedolytic properties and demonstrated efficacy as monotherapy and as part of a combination regimen in treating mild to moderate acne with a favorable tolerability profile. comedolytic properties references 1. saint-léger d, et al. journal of cosmetic dermatology, 2007, 6: 59-65 2. jiang m, qureshi sa. j dermatol sci, 1998, 18: 181-188 3. dupuis d, et al. j invest dermatol, 1984, 82: 353-356 4. piérard g, et al. eur j dermatol, 2002, 4(12): xliv-xlvi 5. geilen cc, et al. arch dermatol res, 1997, 289: 559-566 6. imayama s, et al. arch dermatol, 2000, 136: 1390-1395 7. piérard ge, rougier a. eur j dermatol, 2002, 12: xlvii-xlviii 8. uhoda e, et al. eur j dermatol, 2003, 13: 65 9. bissonnette r, et al. j cosmet dermatol, 2009 mar, 8(1): 19-23 fc17posterlarochezeichnertheuseoflipohydroxy.pdf powerpoint presentation internal use only medical and scien�fic affairs no new safety signals were identified, and adverse events were consistent with the known apremilast safety profile primary outcome: psoriasis severity assessed by the proportion of patients achieving an spga response at week 16 (spga response: a score of 0/1 [clear/almost clear skin] with a ≥ 2-point reduction from baseline) presented at: winter clinical dermatology conference hawaii 2023; january 13–18, 2023; hi, usa © 2023 amgen inc. disclosures and funding statement lf: amgen, galderma, leo pharma, and pfizer – investigator, received honoraria, and advisory board member; pierre fabre and galderma – speaker. eb: amgen – principal investigator; pfizer, regeneron, and sanofi – speaker. rdl: nothing to disclose. ab-f: abbvie, janssen, novartis, pfizer, and sanofi – consultant and received fees and honoraria. sa: amgen, janssen, leo pharma, and novartis – speaker and advisory board member. pm, rko, mp, wz, and zz: amgen – employees and stockholders. la: candela – received research equipment; amgen and celgene – investigator; abbvie, amgen, regeneron, and verrica – consultant. this study was sponsored by amgen inc. writing support was funded by amgen inc. and provided by lakshmi narendra bodduluru, phd, of cactus life sciences (part of cactus communications), and dawn nicewarner, phd, cmpp, employee of and stockholder in amgen inc. pasi-75 response: a ≥ 75% reduction in pasi scores from baseline. pasi, psoriasis area and severity index; spga, static physician’s global assessment. approved oral or injectable therapies for children with moderate to severe psoriasis are limited apremilast, an oral immunomodulator that inhibits pde4, is approved for use in adults with psoriasis, psoriatic arthritis, and oral ulcers associated with behçet’s disease apremilast has shown favorable effects over risks in 706,585 adults globally, across the indications for which it is approved to evaluate how well apremilast works and how safe it is in children with moderate to severe psoriasis that was inadequately controlled by or intolerant to medications applied to the skin key secondary outcome: psoriasis improvement assessed by the proportion of patients achieving a pasi-75 response at week 16 to assess psoriasis severity pasi, psoriasis area and severity index; spga, static physician’s global assessment. efficacy and safety results of apremilast in pediatric patients with moderate to severe plaque psoriasis: 16-week results from sprout, a phase 3, randomized, controlled study loretta fiorillo, md1; emily becker, md2; raul de lucas, md3; anna belloni-fortina, md4; susana armesto, md5; peter maes, ba6; rajneet k. oberoi, bpharm, phd6; maria paris, md6; wendy zhang, md, msc6; zuoshun zhang, phd6; lisa arkin, md7 key takeaways apremilast was well tolerated and effectively reduced psoriasis severity in children aged 6 to 17 years with moderate to severe plaque psoriasis that was inadequately controlled by or intolerant to medications applied to the skin for additional findings, scan the qr code 1stollery children’s hospital, university of alberta, edmonton, alberta, canada; 2driscoll children’s hospital, corpus christi, tx, usa; 3hospital universitario la paz – ppds, madrid, spain; 4azienda ospedale università padova, padova, italy; 5hospital universitario marques de valdecilla, santander, spain; 6amgen inc., thousand oaks, ca, usa; 7university of wisconsin school of medicine and public health, madison, wi, usa amp, adenosine monophosphate; camp, cyclic adenosine monophosphate; il, interleukin; pde, phosphodiesterase; tnf-α, tumor necrosis factor alpha. the percentage of patients in the age and weight categories was similar between apremilast and placebo groups 3x achievement of clear/almost clear skin (spga response) vs 33.1% 11.5% apremilast placebo ~3x vs improvement in disease severity by ≥ 75% (pasi-75 response) 45.4% 16.1% apremilast placebo this phase 3 study included 245 participants from 99 centers in 10 countries (nct03701763) what was our aim? il-17a il-17f il-22 tnf-α il-10 5′-amp apremilast − p d e 4 camp what do we know? what did we do? what were our findings at week 16? week 16 163 patients week 0 week 52 week 66 2: 1 82 patients placebo apremilast fo llo w -u p apremilast apremilast 245 patients randomized (age: 6–17 years) pro-inflammatory mediators anti-inflammatory mediators slide number 1 figure. exposure-adjusted clinical events of special interest, as deemed by the reporter or company, within the 4-year reporting period. exposure-adjusted event rate per 100 pys is the number of events per 45.63 pys of exposure. ibd, inflammatory bowel disease; py, patient-year. clinical events of special interest • exposure-adjusted event rates are reported in the figure infections • of 102 serious infections reported, only 3 were considered related to brodalumab • although no serious fungal infections were reported, 1 new fungal infection (onychomycosis) led to the patient discontinuing brodalumab; there were no new reports of oral candidiasis • one case of tuberculosis, 24 cases of confirmed covid-19, and 2 cases of suspected covid-19 were reported inflammatory bowel disease • no new cases of crohn’s disease were reported (1 case was previously reported in a patient who had symptomatic history before brodalumab initiation) • one case of ulcerative colitis, which was not suspected to be related to brodalumab, was reported malignancies • 37 malignancies were reported in 32 patients (0.81 events/ 100 pys); none were considered related to brodalumab depression and suicide • there were 4 new depression cases reported during year 4; no causality assessments were provided • there were no completed suicides throughout the 4-year report and no new suicide attempts reported (there was 1 previously reported suicide attempt, with no indicated causal relationship between brodalumab and the patient’s attempted self-harm) synopsis • brodalumab is an interleukin-17 receptor a antagonist indicated for moderate-to-severe plaque psoriasis in adult patients with loss of or no response to alternative systemic therapies1 – brodalumab has a boxed warning for suicidal ideation and behavior in the united states, even though pivotal clinical trials and recent pharmacovigilance data do not confirm a causal relationship1-3 – no completed suicides and 1 suicide attempt by a patient with a history of depression occurred during the initial 3-year pharmacovigilance reporting period3 – arthralgia was the most common treatment-specific adverse event (ae) in the 2and 3-year pharmacovigilance reports3,4 methods • pharmacovigilance data reported to ortho dermatologics by us patients and healthcare providers were compiled from august 15, 2017, through august 14, 2021 • the most common aes listed in the brodalumab package insert (incidence ≥1%; arthralgia, headache, myalgia, influenza, diarrhea, oropharyngeal pain, nausea, injection-site reactions, fatigue, neutropenia, and tinea infections) and aes of special interest were assessed as exposure-adjusted rates per 100 patient-years (pys) • brodalumab exposure was estimated as the time between the first and last prescription-dispensing authorization dates. patients with the same initial and last prescription-dispensing authorization date were excluded results commonly reported aes from package insert • data were collected from 4019 us patients and exposure was estimated as 4563 pys • of 2118 unique ae cases, 22% were reported by healthcare providers and 78% by patients • common aes are listed in the table; similar to previous reports,3,4 arthralgia was the most commonly reported ae within the 4-year reporting period (115 cases; 2.52 events/ 100 pys) – of arthralgia cases, 53 and 25 patients continued and discontinued treatment, respectively, whereas treatment status was unknown for 37 patients – of the 4 new cases of arthralgia since the 3-year report, 3 patients were temporarily off brodalumab when their joint pain recurred • there were no new reports of injection-site reactions, fatigue, or neutropenia since the 3-year report brodalumab: 4-year us pharmacovigilance report mark lebwohl,1 andrea murina,2 george han,3 abby jacobson4 1icahn school of medicine at mount sinai, new york, ny; 2tulane university school of medicine, new orleans, la; 3zucker school of medicine at hofstra/northwell, hempstead, ny; 4ortho dermatologics (a division of bausch health us, llc), bridgewater, nj objective • to review the us pharmacovigilance data over a 4-year reporting period to provide insight into the safety of brodalumab for the treatment of moderate-to-severe plaque psoriasis in adults conclusions • these us pharmacovigilance data are consistent with the established safety profile of brodalumab reported in long-term clinical trials and 3-year pharmacovigilance data • no completed suicides occurred throughout the 4-year reporting period, and no new cases of suicide attempts were reported since the 3-year report funding: this study was sponsored by ortho dermatologics. medical writing support was provided by medthink scicom and funded by ortho dermatologics. ortho dermatologics is a division of bausch health us, llc. author disclosures: ml is an employee of mount sinai; receives research funds from: abbvie, amgen, arcutis, avotres, boehringer ingelheim, cara therapeutics, dermavant, eli lilly, incyte, janssen, ortho dermatologics, regeneron, and ucb; and is a consultant for aditum bio, almirall, altrubi, anaptysbio, arcutis, arena pharmaceuticals, aristea therapeutics, arrive technologies, avotres therapeutics, biomx, bms, boehringer ingelheim, brickell biotech, cara therapeutics, castle biosciences, corevitas, dermavant, dr. reddy’s, evelo biosciences, evommune, facilitation of international dermatology education, forte biosciences, foundation for research and education in dermatology, helsinn therapeutics, hexima ltd., leo, meiji seika pharma, mindera, pfizer, seanergy, and verric. am is a speaker for abbvie, amgen, bms, eli lilly, janssen, and ortho dermatologics; and has served as a consultant for bms, janssen, novartis, ortho dermatologics, and ucb. gh is or has been an investigator for athenex, bms, boehringer ingelheim, bond avillion, celgene, eli lilly, novartis, janssen, mc2, pellepharm, pfizer, and ucb; and a consultant, advisor, or speaker for abbvie, boehringer ingelheim, dermtech, eli lilly, incyte, janssen, leo, ortho dermatologics, pfizer, regeneron, sanofi genzyme, sun, and ucb. aj is an employee of ortho dermatologics (a division of bausch health us, llc). references: 1. siliq [package insert]. bausch health us, llc; 2017. 2. lebwohl et al. j am acad dermatol. 2018;78:81-89. 3. lebwohl et al. dermatol ther. 2021;34:e15105. erratum in dermatol ther. 2022;35:e15664. 4. lebwohl et al. dermatol ther (heidelb). 2021;11:173-180. previous presentation information: data included in this poster have been previously presented in full at the fall clinical dermatology conference; october 20-23, 2022; virtual and las vegas, nv. presented at winter clinical dermatology conference hawaii ® • january 13-18, 2023 • kohala coast, hi table. us pharmacovigilance monitoring of brodalumab through 4 years (august 15, 2017–august 14, 2021) ae event, n (r)a event drug related, nb discontinued, n (%)c maintained, n (%)c action unknown/na, n (%)c arthralgia 115 (2.52) 1 25 (22) 53 (46) 37 (32) headache 45 (0.99) 0 6 (13) 25 (56) 14 (31) fatigue 44 (0.96) 1 6 (14) 20 (45) 18 (41) injection-site reaction 35 (0.77) 3 1 (3) 18 (51) 16 (46) diarrhea 33 (0.72) 0 6 (18) 19 (58) 8 (24) myalgia 31 (0.68) 0 6 (19) 18 (58)d 7 (23) nausea 29 (0.64) 0 5 (17) 17 (59) 7 (24) influenza 23 (0.50) 1 9 (39) 7 (30) 7 (30) oropharyngeal pain 21 (0.46) 0 2 (10) 11 (52)e 8 (38) neutropenia 1 (0.02) 0 0 1 (100) 0 tinea infection 0 — — — — ae, adverse event; na, not applicable; r, exposure-adjusted event rate per 100 patient-years. anumber of patients experiencing ae, not total number of aes. brelatedness to brodalumab was based on company-determined causality. ctreatment action taken upon ae occurrence. percentage is event divided by total number of patients experiencing event. done patient increased brodalumab dose. eone patient temporarily stopped taking the drug but planned to resume brodalumab treatment. 2.24 1.14 0.81 0.15 0.04 0 0.00 0.50 1.00 1.50 2.00 2.50 serious infection depression malignancies fungal infection ibd suicide ex po su re -a dj us te d ev en t ra te p er 1 00 p y s skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 472 original research a prospective, multi-center clinical utility study demonstrates that the 40-gene expression profile (40-gep) test impacts clinical management for medicare-eligible patients with highrisk cutaneous squamous cell carcinoma (cscc) eli saleeby, md1, kenneth bielinski, md2, alison fitzgerald, phd3, jennifer siegel, phd3, sherrif ibrahim, md, phd4 1 larkin community hospital, miami, fl 2 skinmd llc, orland park, il 3castle biosciences, inc., friendswood, tx 4 rochester dermatologic surgery, victor, ny; university of rochester medical center, rochester, ny the most common cancer in the united states is non-melanoma skin cancer (nmsc). it has been reported to have a steadily increasing incidence, in part due to enhanced detection methods and an aging population.1–6 cutaneous squamous cell carcinoma (cscc) has recently been noted to account for up to half of nmscs with estimates of 1.8 million new cases per year.2 abstract the incidence and mortality rates of cutaneous squamous cell carcinoma (cscc) in the medicare population are rapidly increasing. the current national guidelines are broad and the available staging systems for stratification are inadequate to accurately guide patient management. a prognostic 40-gene expression profile (40-gep) test has demonstrated both analytical and clinical validity for assessment of metastatic risk of high-risk cscc patients independent of traditional clinicopathologic factors. real-world data have shown that clinicians can identify appropriate patients for 40-gep testing and use this personalized, molecular risk stratification tool to guide risk-aligned clinical planning and patient management. the data herein focuses on 59 medicare-eligible patients (≥65 years of age) enrolled within a multicenter, prospective clinical utility and health outcomes study (utilise) conducted to demonstrate patterns of 40-gep test utilization, distribution of results across clinicopathologic variables, and impact on clinician recommendations for clinical management of high-risk cscc patients. regarding management of patients under-study, more than 80% of clinicians reported that the 40-gep had a positive impact and 42% stated a 40-gep test result was the single most influential factor in determining management plans. overall, 24% of clinicians made changes to their treatment plan after receiving the 40-gep resulta clinical actionability rate comparable to those of currently covered molecular tests for cancer patients. this analysis demonstrates the positive impact the 40-gep is having on clinicians’ assessment of risk for their high-risk cscc patients, which, in line with guidelines, is driving risk-aligned changes in treatment plans. introduction skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 473 studies have also calculated not only a significant increase cscc in the general population, but an even more dramatic increase in the medicare population.4, 7 approximately 6% of cscc patients will develop regional or distant metastatic lesions,3, 5, 8–12 after which prognosis is usually poor, with 5-year survival rates ranging from 26-34% and 10-year survival rates of 16%.13 the total number of deaths resulting from cscc are estimated to be equal to or greater than those attributed to melanoma, due to the large number of cscc diagnoses every year, and account for the majority of nmsc-related deaths.4, 5, 14, 15 risk stratification and staging systems for cscc are based on clinical and pathological features and include the national comprehensive cancer network (nccn) guidelines criteria, the american joint committee on cancer (ajcc) cancer staging manual (8th edition, ajcc8), and the brigham and women’s hospital (bwh) tumor classification system.3, 16–20 these systems are limited in their ability to predict adverse events (i.e. have low positive predictive value [ppv] for metastasis)18–22 and thus pose a challenge for implementing risk-directed patient management. ppv is low for both the nccn and ajcc systems (14%–17%),17–20, 22 and slightly higher for bwh (24%-38%), meaning that many patients categorized as high risk do not develop advanced disease.16, 23 data concerning cscc is not collected in national cancer registries, contributing to the limitations of the efforts of staging systems at prognostication and making knowledge of costs associated with procedures utilized for this population scarce. one study did analyze 999 cscc patients collected from truven marketscan® claims databases from 20122016 who had at least one lymph node dissection, ≥1 chemotherapy with radiation therapy in ≥2 treatment fields, or a metastasis.24 with an average follow-up time of 16 months, the average total costs were $18,409.05 per-patient-per-month (pppm) and average cscc-specific costs were $7,385.82 pppm. the authors compared these costs to that of metastatic melanoma, which was reported to have a total cost of $12,111 pppm in 2013. equally important, due to the lack of standardized care for highrisk cscc patients, improved risk stratification methods would reduce unnecessary procedures for a patient population that is often elderly and at higher risk for complications. given the discordance between staging systems and the generalization of treatment guidelines, 21, 22, 25, 26 there has been a clinical unmet need requiring better methods to identify truly highrisk lesions with regard to outcomes, particularly molecular biomarkers that can be objectively evaluated. gene expression profile (gep) signatures have been shown to have powerful, independent, risk-stratification (aka prognostic) value for many tumor types, such as cutaneous melanoma, uveal melanoma, breast, prostate and others, improving riskstratification treatment plan decisions by complementing staging based on clinicopathologic factors and have shown a significant impact on clinical management.27– 31 in these diseases, gep signatures help improve risk estimates, independent of or in combination with traditional clinical staging, and are impactful in determining management strategies within established clinical guidelines. consistent with this clinical actionability, many gep signatures are now standard of care in oncology and covered by national insurance providers, including medicare. a 40-gene expression profile (40-gep) test has been validated to improve metastasis risk prediction in highrisk cscc patients (high risk cscc is defined as patients diagnosed with invasive cscc skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 474 and the presence of one or more clinicopathologic risk factors) using archival, formalin-fixed paraffin-embedded (ffpe) primary cscc tissue.32 this test stratifies clinicopathologically-confirmed high-risk cscc tumors into three risk groups based on low (class 1), moderate (class 2a), and high (class 2b) risk for regional or distant metastasis at 3 years after diagnosis.32 a substantially higher ppv (60.0%) was found for the 40-gep test for class 2b relative to that found for the ajcc8 and bwh staging systems, while maintaining a negative predictive value (npv) of approximately 90.0% (which is similar to that of the ajcc8 and bwh systems).32 further, several studies have demonstrated that use of the 40-gep test results impacted management decisions in a clinically and statistically significant and risk-appropriate manner for high-risk cscc patient scenarios.33–36 the overarching goal of this ongoing, multicenter, prospective clinical utility and health outcomes study (utilise) is to demonstrate patterns of test utilization, the distribution of results across clinicopathologic variables, and the impact on clinician recommendations for clinical management of high-risk cscc patients. this analysis focuses on the medicare-eligible, clinically tested population to evaluate the utility of 40gep results on clinician recommendations regarding therapeutic management for their high-risk cscc patients. to evaluate the utility of the 40-gep in the medicare-eligible, clinically tested population (≥65 years old), patient clinicopathologic factors, 40-gep test results and changes in clinical management were recorded and analyzed in a prospective, multi-center clinical study (clinical utility and health outcomes study [utilise]). the study cohort consisted of patients diagnosed with a primary cscc who qualified for 40-gep testing and elected to be part of the clinical care plan. institutional review board approval was obtained at each institution and all patients were required to meet study inclusion criteria as listed in table 1 along with having a signed informed consent secured. the study consisted of two sequential phases: the lead-in phase and the clinical utility phase (figure 1). the lead-in phase opened to enrollment of patients on august 31, 2021. during the lead-in phase, clinicians recorded a treatment plan assessment before receiving the 40-gep test results for at least five patients. details of patient demographics, clinicopathological features, disease management and outcomes were collected via a review of medical records and entered into an electronic case report form. after completion of the treatment plan assessment for these five patients, clinicians were then able to enroll new patients into the clinical utility phase. the ongoing clinical utility phase began enrolling patients on november 24, 2021. data collection for the clinical utility phase was identical to the lead-in phase with the addition of a second treatment assessment plan to be completed after receipt of the 40gep results (i.e., post-test). patient management decisions and outcomes were reported as described above. patients were either enrolled in the lead-in phase or the clinical utility phase, but not both. statistical analysis wilcoxon signed rank tests with continuity correction were used to compare preand post-40-gep test treatment impact changes methods skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 475 table 1. patient eligibility criteria for utilise inclusion criteria exclusion criteria patient is willing and able to provide informed consent. direct employees and family members of an investigator newly diagnosed cscc with no more than six months before patient consent, with pathologically confirmed invasive cscc for whom the clinician has determined the 40-gep to be clinically appropriate (as previously described36) and will order the 40-gep test as part of their clinical care patient whose primary cscc tumor is not considered invasive (e.g., bowens disease) or not pathologically confirmed as invasive cscc patient must be ≥18 years of age at time of diagnosis of the tumor under study. patient who does not meet the guidelines for testing with 40-gep36 or is enrolled in another castle biosciences inc. study. patient must likely follow up with enrolling clinicians for three years, or enrolling clinicians must have access to relevant medical records from other medical providers. patient who is in the investigator’s opinion, unlikely to survive the threeyear study duration in the absence of cscc. figure 1. study schematic of utilise (the clinical utility and health outcomes study of the prognostic 40-gep test) skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 476 figure 2. consort diagram for enrollment of medicare-eligible patients figure 3. do 24% of clinicians made changes in patient management due to 40-gep testing and 42% reported 40-gep results as the most influential factor in determining the management plan for their patient skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 477 table 2. patient demographics of clinical utility cohort of medicare-eligible patients feature clinical utility cohort, n (%) medicare-eligible patients 59 (100) age: average years (range) 78.2 (65-90)* male 38 (64.4) location on head or neck 43 (72.9) patient immunosuppressed 2 (3.4) neurologic symptoms at tumor site 1 (1.7) chronic inflammation at tumor site 2 (3.4) tumor diameter ≥2cm 21 (35.6) rapidly growing tumor 6 (10.2) poorly defined borders 10 (17.2) poor differentiation 1 (1.7) depth of invasion** beyond subcutaneous fat 1 (1.7) clark level iv or v 18 (30.5) breslow’s thickness ≥2mm 3 (5.1) lymphovascular invasion 1 (1.7) perineural invasion 2 (3.4) 40-gep result class 1 52 (88.1) class 2a 7 (11.9) class 2b# -- *to maintain confidentiality, any age >90 was reported as 90 **investigators were allowed to report depth of invasion using various options # no class 2b test results were observed at the time of analysis skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 478 with alpha set at 0.05. all data analysis was performed using open-access packages running in r (v4.1.2). five clinical sites and eleven unique clinicians have enrolled patients qualifying for inclusion in the current analyses. eight (72%) clinicians were board certified dermatologists (with an average/median practice time of 21.6 years) of which seven identified as mohs surgeons, and three were dermatologybased physician assistants who had been practicing in dermatology for an average of 3.3 years. at the time of this current analysis (october 2022), 140 patients were enrolled in the study and had received their gep test result (figure 2). twenty-one patients were excluded due to insufficient tissue for testing or other technical issue, patient withdrawal due to relocation, or post-enrollment site review indicating failure to qualify. the focal population for current analysis is the medicare population, therefore patients <65 years of age were also excluded (n=22), leaving 97 patients for potential analysis. these 97 patients were inclusive of n=31 patients enrolled in the lead-in phase and n=59 patients in the clinical utility phase. to note, five patients in the latter cohort had been excluded for further analysis due to incomplete treatment assessment forms and two patients due to a multi-gene failure received from analysis of their tumor biopsy tissue. lead-in cohort completion of the lead-in phase ensured that the site/clinicians were familiar and comfortable with use of the 40-gep test and data entry before moving to the clinical utility phase. at the time of analysis, the lead-in cohort included 31 medicare-eligible patients with the average age being 76.4 years old (±7.3). the median follow-up time for these patients was 41.7 weeks. 81% of the patients in this cohort had ≥2 risk factors (mean=2.5) with location on the head or neck (71%), depth of invasion (clark level ≥iv, 71%), and tumor diameter ≥2cm (36%) being the three most observed clinicopathologic high-risk factors. 90.3% of this cohort underwent mohs micrographic surgery (mms) as their definitive surgery. this high-risk cscc cohort was comprised of 68% 40-gep class 1, 25% class 2a, and 6% class 2b cases. at the time of analysis, the one patient who had regional metastasis after definitive surgery had received a class 2a result. based on 40gep class results and clinicopathologic risk factor distribution, participating clinicians received ample experience with prognostic molecular testing for individual patients. clinical utility cohort the clinical utility cohort analyzed in this study included 59 medicare-eligible patients with the average age being 78.2 years old (±7.9) (table 2). the median follow-up timeframe for these patients was 22.5 weeks. 40-gep tests were ordered by the treating clinicians for patients diagnosed with cutaneous squamous cell carcinoma (scc) with one or more risk factors. 39.7% of the patients had 1 risk factor, 37.9% had 2 risk factors, and the remaining had more than 2 risk factors. location on the head or neck (73%), tumor diameter ≥2cm (36%), and depth of invasion (clark level ≥iv, 31%) were the three most common clinicopathologic high-risk factors observed. 96.6% of this cohort underwent mms as their definitive treatment. this high-risk cscc cohort was comprised of 88% 40-gep class 1 and 12% class 2a cases. notably, 82.7% of clinicians reported a valuable impact to their patient management results skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 479 when incorporating 40-gep results (chisquare statistic=15.6; p-value<0.001) (figure 3a); wherein 58.6% and 24.1% gained an increased confidence in and made changes to their original treatment plan, respectively. when analyzing these data by 40-gep class result, 64.7% of clinicians reported increased confidence in their pre-test treatment plan and 17.6% reported a direct impact on treatment decisions for their patients receiving a class 1 result. for clinicians whose patients received a class 2a result, 14.3% reported increased confidence in their pre-test treatment plan and 71.4% reported a direct impact on treatment plans. positive changes in patient attitude after receiving a 40-gep class 2a test result were also reported (14.3%). to further support the reported changes in management, 42.4% of clinicians noted a 40-gep test result as the most influential factor in guiding the management of their patient (figure 3b). this cohort was used to evaluate 40-gepdriven effects on treatment action plans and perception of risk by comparing clinician answers between the preand post-gep treatment assessment forms. based on the low-risk class 1 results, clinician perception of metastatic likelihood decreased in a riskaligned manner for 25.5% of patients (table 3). in contrast, clinician perception of metastasis risk likelihood increased for 71.4% of patients that received a class 2a result for an overall change in perception of metastatic likelihood of 31.0% (p<0.001). all changes to perception of risk for development of nodal or distant metastasis were aligned with 40-gep class result. overall, there was a statistically significant and clinically impactful change in intensity of management as a consequence of 40-gep testing (22.4%, p=0.003). the intensity of management was decreased for 15.7% patients from moderate to low intensity due to a class 1 test result. class 2a results increased the preto post-test management from low to moderate intensity or from moderate to high for a total of 57.1% of patients (table 3). management decisions for patients with cscc are determined by the clinician’s evaluation of the risk of disease progression. this evaluation can be challenging for implementing risk-appropriate high-risk cscc patient management and lead to variability in outcomes due to the limitations of clinical and pathologic based riskassessment and staging systems in predicting poor outcomes, coupled with the broad range of treatment options outlined in guidelines. the 40-gep was developed as an objective, personalized, molecular test to better identify patients at risk for regional/nodal or distant metastasis, such that they receive more accurate risk-aligned treatment plans. the 40-gep has proven to provide improved stratification independent of traditional clinicopathologic risk factors and staging systems.32, 37 the clinically tested population analyzed in this manuscript is focused on the medicareeligible population primarily because the majority of cscc patients with high-risk clinicopathologic risk factors are older than 65 years of age with a majority of their csccs occurring on the head and neck, both are factors that elevate the morbidity arising from adjuvant treatments. thus, as an objective, molecular test that better predicts poor outcomes for high-risk cscc compared to clinicopathologically based risk-assessment or staging systems, use of the 40-gep should efficiently reduce unnecessary interventions, improve identification of patients who may benefit from these interventions and have an overall discussion skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 480 table 3. clinicians’ perception of metastasis likelihood and overall management intensity changes with 40-gep results in preand post-test comparison clinician perception of risk: what is the patient’s risk of developing nodal or distant metastasis? 40-gep class 1 40-gep class 2a pre-gep post-gep n % of class 1* pre-gep post-gep n % of class 2a <5% <5% 37 72.5% <5% 10-30% 3 42.8% 5-10% <5% 12 23.5% 5-10% 5-10% 2 28.6% 5-10% 5-10% 1 2.0% 5-10% 10-30% 2 28.6% 10-30% <5% 1 2.0% gep-driven change: 13 25.5% gep-driven change: 5 71.4% overall gep-driven change in risk perception 18/58 = 31.0% (p<0.001) intensity of management: what is the overall management recommendation for this patient? 40-gep class 1 40-gep class 2a pre-gep post-gep n % of class 1* pre-gep post-gep n % of class 2a low low 36 70.6% low low 1 14.3% low moderate 1 2.0% low moderate 3 42.8% moderate low 8 15.7% moderate moderate 1 14.3% moderate moderate 6 11.8% moderate high 1 14.3% high high 1 14.3% gep-driven change: 9 17.7% gep-driven change: 4 57.2% overall gep-driven change in intensity of management: 13/58 = 22.4% (p=0.0033) *n=1 case with no response skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 481 improvement in healthcare resource utilization. use of the 40-gep is recommended for patients with primary cscc having one or more high-risk factors. the real-world clinical use population for 40-gep testing (hooper, et al,.36) does align with the utilise population both by number of risk factors and in percent of patients ≥65 years old (data presented here and castle biosciences data on file). while the focus of this analysis was on decision making preand post-40 gep results a limitation to this prospective study is that a formal assessment of patient outcomes could not be performed due to abbreviated follow-up time for both cohorts. however, one nodal metastasis was observed in the leadin cohort, which, as expected, was observed in the higher risk 40-gep class, class 2a. while several clinician specialty types may be involved in the multidisciplinary care team for patients with high-risk cscc, dermatologists or dermatologists/mohs surgeons do serve as the hub for patient management decisions. although highly experienced clinicians were involved in this study, a potential limitation is the minimal number currently participating (n=11) for the clinical utility cohort. however, their specialties were encompassing of those most accessed for initial evaluation and treatment of high-risk cscc patients, and with their ‘graduation’ from the lead-in phase, confidence in their assessment of how to implement the results of the 40-gep can be considered steadfast. it is important to note that all clinicians participating in this study practiced in dermatology, 72% are boardcertified dermatologists mohs surgeons, indicating that this prospective study represents the same clinician type utilizing the test and making management decisions for patients with this nonmelanoma skin cancer type. this analysis of the prospective utilise study demonstrates the positive impact of 40gep test results on clinician recommendations and actions for management of their medicare-eligible highrisk cscc patients. hooper, et al.,36 identified that the 40-gep test had a significant impact on clinician decision making in a real-world setting, particularly for those ≥65 years of age. this data led us to analyze the impact on treatment plans within the medicareeligible population in the prospective utilise study. the results of this study identified the 40-gep test as the single most influential factor in determining management plans for 42% of patients, along with a test result positively impacting patient management for over 80% of patients. importantly, 15.7% of patients with a class 1 result had a de-escalation in management that was aligned with their lower predicted risk of metastasis compared to clinicopathologic factors alone. consistent with this alignment, 57.2% of patients with a class 2a result had an escalation in management plans. these data show that risk-aligned changes in management planning are made and that these clinicians do incorporate the objective biological information that the 40-gep test provides and use the information to prevent over treatment in those with a biologically low risk of metastasis and appropriately elevate the treatment in those with a greater biologic risk of metastasis to prevent poor outcomes. these clinical treatment plan actions are not surprising given that gep tests have been widely used and advocated for as riskstratification factors that influence treatment plans in various cancer types.38–47 specifically, the results described here and within hooper et al.,36 mirror those of other risk-stratification gene expression profile tests (table 4). for example, for stage i-ii, skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 482 table 4. overall management change in patients tested with the 40-gep compared to commonly used medicare covered prognostic gep tests in other cancers publication gep (cancer) intended use management change current 40-gep (cscc) to guide treatment decisions in patients with cscc with one or more high-risk factors 24% soliman 202039 70-gep (breast) to guide chemotherapy decisions in patients with early-stage breast cancer 24% *martin 201540 50-gep (breast) to guide adjuvant treatment selection in patients with early-stage breast cancer 20% asad 200843 21-gep (breast) to guide adjuvant treatment selection in patients with early-stage breast cancer 44% gore 201738 22-gep (prostate) to guide decisions about adjuvant radiation therapy 18% badani 202141 17-gep (prostate) to guide treatment decisions, including active surveillance, prostatectomy, and radiation therapy 18% lee 202142 23-gep (lung) to guide invasive procedures versus surveillance in low/intermediate risk of lung malignancy 25% skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 483 hormone receptor-positive, her2-negative breast cancer patients, the medicare-covered 70-gene risk of recurrence signature (70-gs) impact trial reported a 24% change in chemotherapy treatment recommendations post-70-gs results39 and a study by martín et al.,40 reported a similar change in overall treatment recommendations (20%) post-50gep results. another medicare-covered gep test, the 21-gep, has been reported to impact treatment decisions in 44% of breast cancer patients43 and tailorx trial results demonstrated a net savings of $49 million per year.48 in a medicare-eligible enriched cohort, the 22-gep for prostate cancer, another medicare-covered gep test, reported an 18% change in treatment recommendation for adjuvant radiation therapy and less anxiety post-test results among patients.38 the 17-gene expression assay test for prostate cancer reported a 85% increase in urologists confidence in recommending treatments with incorporation of test results and an overall 18% change in recommendations between active surveillance and immediate treatment posttest results.41 the 23-gep test demonstrated that within the cohort of patients with low/intermediate risk lung nodules, 25% had a change in management plan from invasive procedure to surveillance when receiving a negative 23-gep result.42 in summary, gep tests help to 1) identify patients at risk for poor outcomes or those who may be good candidates for adjuvant therapy, 2) prevent unwarranted treatments, 3) increase savings and better allocation of healthcare resources, 4) increase confidence among clinicians and decrease anxiety among patients. in this analysis of the prospective clinical utility and health outcomes study (utilise), the 40-gep positively impacts a majority of clinicians’ assessments of risk for their medicare eligible patients with high-risk cscc, which, in line with guidelines, is driving risk-aligned changes in treatment plans. it is also noteworthy that the clinical actionability rates of the 40-gep for cscc are comparable to those of currently covered molecular tests for cancer patients. overall, 40-gep results can help focus treatment options in a risk-appropriate manner, allowing for optimized utilization of healthcare resources and assisting in the development of a more standardized approach to the management of high-risk cscc. conflict of interest disclosures: es and kb participated as investigators for castle biosciences, inc. (cbi) during this study; af and js are employees and options holders for cbi; si is an investigator, advisor, and speaker for cbi. funding: materials and funding for this study were provided by cbi corresponding author: sherrif ibrahim, md, phd 7400 pittsford victor rd victor, ny 14564 email: sherrif_ibrahim@urmc.rochester.edu references: 1. waldman a, schmults c: cutaneous squamous cell carcinoma. hematol oncol clin north am 33:1–12, 2019 2. our new approach to a challenging skin cancer statistic the skin cancer foundation [internet][cited 2022 sep 5] available from: https://www.skincancer.org/blog/our-newapproach-to-a-challenging-skin-cancerstatistic/ 3. national comprehensive cancer network: squamous cell skin cancer, nccn guidelines version 2.2022, in nccn clinical practice guidelines in oncology [internet], 2022available from: https://www.nccn.org/professionals/physician _gls/pdf/squamous.pdf 4. rogers hw, weinstock ma, feldman sr, et al: incidence estimate of nonmelanoma skin cancer (keratinocyte carcinomas) in the us conclusion skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 484 population, 2012. jama dermatol 151:1081, 2015 5. karia ps, han j, schmults cd: cutaneous squamous cell carcinoma: estimated incidence of disease, nodal metastasis, and deaths from disease in the united states, 2012. j am acad dermatol 68:957–966, 2013 6. muzic jg, schmitt ar, wright ac, et al: incidence and trends of basal cell carcinoma and cutaneous squamous cell carcinoma: a population-based study in olmsted county, minnesota, 2000 to 2010. mayo clin proc 92:890–898, 2017 7. lukowiak tm, aizman l, perz a, et al: association of age, sex, race, and geographic region with variation of the ratio of basal cell to cutaneous squamous cell carcinomas in the united states. jama dermatol 156:1192, 2020 8. feinstein s, higgins s, ahadiat o, et al: a retrospective cohort study of cutaneous squamous cell carcinoma with lymph node metastasis: risk factors and clinical course. dermatol surg 45:772–781, 2019 9. thompson ak, kelley bf, prokop lj, et al: risk factors for cutaneous squamous cell carcinoma outcomes: a systematic review and meta-analysis. jama dermatol 152:419– 428, 2016 10. belkin d, carucci ja: mohs surgery for squamous cell carcinoma. dermatol clin 29:161–174, 2011 11. yom ss: integrating the management of nodal metastasis into the treatment of nonmelanoma skin cancer. semin radiat oncol 29:171–179, 2019 12. karia ps, morgan fc, ruiz es, et al: clinical and incidental perineural invasion of cutaneous squamous cell carcinoma. jama dermatol 153:781, 2017 13. kwon s, dong z, wu pc: sentinel lymph node biopsy for high-risk cutaneous squamous cell carcinoma: clinical experience and review of literature. world j surg oncol 9:80, 2011 14. brantsch kd, meisner c, schönfisch b, et al: analysis of risk factors determining prognosis of cutaneous squamous-cell carcinoma: a prospective study. lancet oncol 9:713–720, 2008 15. schmults cd, karia ps, carter jb, et al: factors predictive of recurrence and death from cutaneous squamous cell carcinoma: a 10-year, single-institution cohort study. jama dermatol 149:541, 2013 16. amin mb, greene fl, edge sb, et al: the eighth edition ajcc cancer staging manual: continuing to build a bridge from a population-based to a more “personalized” approach to cancer staging. ca cancer j clin 67:93–99, 2017 17. amin mb, edge s, greene f, et al (eds): ajcc cancer staging manual, eighth edition. new york, ny, springer international publishing, 2017 18. ruiz es, karia ps, besaw r, et al: performance of the american joint committee on cancer staging manual, 8th edition vs the brigham and women’s hospital tumor classification system for cutaneous squamous cell carcinoma. jama dermatol 155:819, 2019 19. jambusaria-pahlajani a, kanetsky pa, karia ps, et al: evaluation of ajcc tumor staging for cutaneous squamous cell carcinoma and a proposed alternative tumor staging system. jama dermatol 149:402, 2013 20. karia ps, jambusaria-pahlajani a, harrington dp, et al: evaluation of american joint committee on cancer, international union against cancer, and brigham and women’s hospital tumor staging for cutaneous squamous cell carcinoma. j clin oncol 32:327–334, 2014 21. roscher i, falk rs, vos l, et al: notice of retraction and replacement: roscher et al. validating 4 staging systems for cutaneous squamous cell carcinoma using populationbased data: a nested case-control study. jama dermatol . 2018;154(4):428-434. jama dermatol 154:1488, 2018 22. karia ps, morgan fc, califano ja, et al: comparison of tumor classifications for cutaneous squamous cell carcinoma of the head and neck in the 7th vs 8th edition of the ajcc cancer staging manual. jama dermatol 154:175, 2018 23. lydiatt wm, patel sg, o’sullivan b, et al: head and neck cancers-major changes in the american joint committee on cancer eighth edition cancer staging manual: head and neck cancers-major 8th edition changes. ca cancer j clin 67:122–137, 2017 24. ruiz es, chen c-i, deering k, et al: treatment patterns and costs in cutaneous squamous cell carcinoma (cscc) patients with nodal dissection, chemotherapy, and/or radiation therapy. j clin oncol 36:e18703– e18703, 2018 25. chu mb, slutsky jb, dhandha mm, et al: evaluation of the definitions of “high-risk” skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 485 cutaneous squamous cell carcinoma using the american joint committee on cancer staging criteria and national comprehensive cancer network guidelines. j skin cancer 2014:1–8, 2014 26. cañueto j, burguillo j, moyano-bueno d, et al: comparing the eighth and the seventh editions of the american joint committee on cancer staging system and the brigham and women’s hospital alternative staging system for cutaneous squamous cell carcinoma: implications for clinical practice. j am acad dermatol 80:106-113.e2, 2019 27. colman h, zhang l, sulman ep, et al: a multigene predictor of outcome in glioblastoma. neuro oncol 12:49–57, 2010 28. francis p, namlos hm, muller c, et al: diagnostic and prognostic gene expression signatures in 177 soft tissue sarcomas: hypoxia-induced transcription profile signifies metastatic potential. bmc genomics 8:73, 2007 29. onken md, worley la, char dh, et al: collaborative ocular oncology group report number 1: prospective validation of a multigene prognostic assay in uveal melanoma. ophthalmology 119:1596–1603, 2012 30. paik s, shak s, tang g, et al: a multigene assay to predict recurrence of tamoxifentreated, node-negative breast cancer. n engl j med 351:2817–26, 2004 31. gerami p, cook rw, wilkinson j, et al: development of a prognostic genetic signature to predict the metastatic risk associated with cutaneous melanoma. clin cancer res off j am assoc cancer res 21:175–183, 2015 32. wysong a, newman jg, covington kr, et al: validation of a 40-gene expression profile test to predict metastatic risk in localized high-risk cutaneous squamous cell carcinoma. j am acad dermatol 84:361– 369, 2021 33. teplitz r, giselle p, litchman gh, et al: impact of gene expression profile testing on the management of squamous cell carcinoma by dermatologists. j drugs dermatol jdd 18:980–984, 2019 34. litchman gh, fitzgerald al, kurley sj, et al: impact of a prognostic 40-gene expression profiling test on clinical management decisions for high-risk cutaneous squamous cell carcinoma. curr med res opin 1–6, 2020 35. au jh, hooper pb, fitzgerald al, et al: clinical utility of the 40-gene expression profile (40-gep) test for improved patient management decisions and disease-related outcomes when combined with current clinicopathological risk factors for cutaneous squamous cell carcinoma (cscc): case series. dermatol ther 12:591– 597, 2021 36. hooper pb, farberg as, fitzgerald al, et al: real-world evidence shows clinicians appropriately use the prognostic 40-gene expression profile (40-gep) test for highrisk cutaneous squamous cell carcinoma (cscc) patients. cancer invest 1–12, 2022 37. ibrahim sf, kasprzak jm, hall ma, et al: enhanced metastatic risk assessment in cutaneous squamous cell carcinoma with the 40-gene expression profile test. future oncol 18:833–847, 2022 38. gore jl, du plessis m, santiago‐jiménez m, et al: decipher test impacts decision making among patients considering adjuvant and salvage treatment after radical prostatectomy: interim results from the multicenter prospective pro‐impact study. cancer 123:2850–2859, 2017 39. soliman h, shah v, srkalovic g, et al: mammaprint guides treatment decisions in breast cancer: results of the impact trial. bmc cancer 20:81, 2020 40. martín m, gonzález-rivera m, morales s, et al: prospective study of the impact of the prosigna assay on adjuvant clinical decisionmaking in unselected patients with estrogen receptor positive, human epidermal growth factor receptor negative, node negative earlystage breast cancer. curr med res opin 31:1129–1137, 2015 41. badani kk, kemeter mj, febbo pg, et al: the impact of a biopsy based 17-gene genomic prostate score on treatment recommendations in men with newly diagnosed clinically prostate cancer who are candidates for active surveillance. urol pract 2:181–189, 2015 42. lee hj, mazzone p, feller-kopman d, et al: impact of the percepta genomic classifier on clinical management decisions in a multicenter prospective study. chest 159:401–412, 2021 43. asad j, jacobson af, estabrook a, et al: does oncotype dx recurrence score affect the management of patients with early-stage breast cancer? am j surg 196:527–9, 2008 44. plasseraud km, cook rw, tsai t, et al: clinical performance and management outcomes with the decisiondx-um gene skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 486 expression profile test in a prospective multicenter study. j oncol 2016:5325762, 2016 45. berger ac, davidson rs, poitras jk, et al: clinical impact of a 31-gene expression profile test for cutaneous melanoma in 156 prospectively and consecutively tested patients. curr med res opin 32:1599–1604, 2016 46. yip l: molecular markers for thyroid cancer diagnosis, prognosis, and targeted therapy. j surg oncol 111:43–50, 2015 47. batista r, vinagre n, meireles s, et al: biomarkers for bladder cancer diagnosis and surveillance: a comprehensive review. diagn basel switz 10, 2020 48. mariotto a, jayasekerea j, petkov v, et al: expected monetary impact of oncotype dx score-concordant systemic breast cancer therapy based on the tailorx trial. jnci j natl cancer inst 112:154–160, 2019 skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 534 brief article identifying inflammatory gene expression signatures for skin and soft tissue infections jennifer e. yeh, md, phd1,2, marcelo pereira da silva, bs3, adam b. raff, md, phd4, ruth k. foreman, md, phd5 1 harvard combined dermatology residency training program, boston, ma 2 stanford university school of medicine, department of dermatology, palo alto, ca 3 massachusetts general hospital, cutaneous biology research center, boston, ma 4 beth israel lahey health, department of dermatology, boston, ma 5 massachusetts general hospital, department of pathology, boston, ma skin and soft tissue infections (sstis) are one of the most common reasons to seek medical care in the united states. cellulitis accounts for ~60% of sstis, with 14.5 million cases annually in the united states accounting for $3.7 billion in healthcare costs.1 sstis are frequently misdiagnosed abstract background: misdiagnosis of skin and soft tissue infections (sstis) due to clinical mimics can result in delay of care, unnecessary antibiotic exposure, and inappropriate hospitalization. comprehensive screening of inflammatory genes in sstis could identify biomarkers to distinguish sstis from mimics. methods: we performed a search of the mgh james homer wright pathology laboratories database from 2008-2018 for diagnoses of necrotizing fasciitis, cellulitis, and stasis dermatitis, yielding 103 cases. diagnoses were verified by chart review and categorized by discharge diagnosis. three samples from each category, along with three controls from location-matched skin were selected for further study. mrna isolated from paraffinembedded skin biopsies was analyzed by nanostring, with 594 inflammatory genes profiled. results: we identified differentially expressed genes between necrotizing fasciitis, cellulitis, and infectious cases (necrotizing fasciitis and cellulitis) compared to non-infectious stasis dermatitis. differentially upregulated genes in sstis included those with known roles in inflammation (cxcr2, il6, ifi16, tnfrsf1b) and transcriptional regulation (bcl3, mbp). we also identified differential upregulation of genes not previously associated with sstis including s100a8, s100a9, mcl1, cd14, and ltf. conclusion: we characterized transcriptomic signatures of severe and moderate sstis compared to stasis dermatitis and normal skin from the lower extremities. though limited by small sample size, these data support the utility of a prospective study analyzing outcomes of patients diagnosed with sstis based on gene expression signatures. identifying sstispecific gene expression signatures could help differentiate true skin infections from noninfectious inflammatory skin conditions, facilitating more accurate diagnoses and improving patient care. introduction skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 535 due to clinical overlap with inflammatory dermatoses (e.g., stasis dermatitis), resulting in delay of effective care, unnecessary antibiotic exposure, and inappropriate hospitalization.2 misdiagnosis is partially due to an incomplete understanding of ssti biology leading to ineffective diagnostic strategies. sstis are thought to be mediated by toxin-induced inflammatory pathways3; however, published literature lacks comprehensive screening of inflammatory genes in sstis. identifying ssti-specific gene expression signatures could help differentiate true skin infections from inflammatory mimics, thereby reducing misdiagnosis and broadening understanding of the pathophysiology to identify potential therapeutic targets. we performed a search of the mgh james homer wright pathology laboratories database from 2008-2018 for diagnoses of necrotizing fasciitis, cellulitis, and stasis dermatitis, yielding 103 cases. diagnoses were verified by chart review and categorized by discharge diagnosis. three samples from each category, along with three controls from location-matched skin were selected for further study. mrna isolated from paraffinembedded skin biopsies was analyzed by nanostring, with 594 inflammatory genes profiled. one hundred thirty-four cases were identified and verified by dermatologist chart review of discharge diagnosis and dermatopathologist review of skin biopsies, yielding 103 cases which were filtered by lower extremity because this location is common for ssti mimics, resulting in 71 cases (figure 1). we confirmed necrotizing fasciitis cases with imaging evidence of subcutaneous air and cellulitis cases with positive bacterial data by culture or gram stain. cases with concomitant clinical scenarios such as osteomyelitis, immunosuppression, implanted hardware, and neutrophilic dermatoses were excluded. for this pilot study, three samples from each diagnosis were chosen for further cytokine interrogation. cultured bacteria from these three cases included methicillin-sensitive staphylococcus aureus and klebsiella oxytoca. additionally, three normal skin controls from location-matched skin and agematched cases (+/10 years) were selected to account for background gene expression. slides were reviewed to confirm the histopathological diagnoses in selected cases (rkf). mrna from ffpe skin biopsy samples was analyzed by nanostring, and 594 inflammatory and immunologic signaling genes were profiled. raw data were normalized to gusb expression. t-tests were performed between infectious cases (necrotizing fasciitis and cellulitis) and noninfectious stasis dermatitis to identify candidate genes (p < 0.05). a heatmap was plotted with the resulting genes (figure 2). differentially upregulated genes in both necrotizing fasciitis and cellulitis included those with known roles in inflammation (cxcr2, il6, ifi16, tnfrsf1b), transcription regulation (bcl3, mbp, socs3), and complement activation (c1qb, c1qa, cr1). neutrophil recruitment by cytokines (il1a, il1b, il6, tnf) and chemokines (cxcl1, cxcl2, cxcl5, cxcl8) is thought to be a key component of the immune response in sstis.4 we also identified differential upregulation of genes not previously associated with sstis methods results skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 536 figure 1. flowchart of case selection for small-scale pilot study. skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 534 figure 2. a) heatmap of differentially expressed genes between infectious (necrotizing fasciitis and cellulitis) vs non-infectious (stasis dermatitis) cases. b) list of differentially expressed genes with associated p-values. including s100a8, s100a9, mcl1, cd14, and ltf. s100a8 and s100a9 are calciumbinding proteins which form an antimicrobial complex secreted by neutrophils during inflammation.5 mcl1 is upregulated during phagocytosis to protect macrophages from apoptosis.6,7 cd14 recognizes lipopolysaccharides in bacterial membranes.8 ltf helps in antimicrobial defense by competing with microbes for iron.9 here, we characterized transcriptomic signatures of severe and moderate sstis compared to a common clinical mimic, stasis discussion skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 535 dermatitis, identifying known and novel genes involved in inflammatory processes and infection. although limited by its small scale, our study identified additional genes beyond what was previously identified in another transcriptomics study comparing bacterial cellulitis to normal-skin controls.10 though limited in sample size, these data represent a pilot study in the understanding if ssti gene regulation and support the utility of a prospective study analyzing patient immune signatures in conjunction with histology to differentiate sstis from clinical mimics. this work could inform innovative strategies that would fundamentally change ssti management by providing rapid, pointof-care, objective diagnostics. identification of tissue-specific and systemic biomarkers in patients with sstis may allow prognostic stratification to guide choice of therapeutics. overall, improved diagnosis for sstis will help reduce unnecessary hospitalizations, antibiotic overuse, and healthcare costs and complications. conflict of interest disclosures: none funding: mgh wellman center for photomedicine early discovery fund grant corresponding author: ruth k. foreman, md, phd department of pathology, dermatopathology 55 fruit st, warren 8 boston ma 02114 phone: 617-726-8490 email: rkforeman@partners.org references: 1. hersh al, chambers hf, maselli jh, gonzales r. national trends in ambulatory visits and antibiotic prescribing for skin and soft-tissue infections. arch intern med. 2008;168(14):1585-91. 2. weng qy, raff ab, cohen jm, et al. costs and consequences associated with misdiagnosed lower extremity cellulitis. jama dermatol. 2017;153(2):141-6. 3. hansen mb, rasmussen ls, svensson m, et al. association between cytokine response, the lrinec score and outcome in patients with necrotising soft tissue infection: a multicentre, prospective study. sci rep. 2017;7:42179. 4. ley k, laudanna c, cybulsky mi, nourshargh s. getting to the site of inflammation: the leukocyte adhesion cascade updated. nat rev immunol. 2007;7(9):678-89. 5. striz i, trebichavsky i. calprotectin a pleiotropic molecule in acute and chronic inflammation. physiol res. 2004;53(3):24553. 6. steimer da, boyd k, takeuchi o, et al. selective roles for antiapoptotic mcl-1 during granulocyte development and macrophage effector function. blood. 2009;113(12):2805-15. 7. koziel j, maciag-gudowska a, mikolajczyk t, et al. phagocytosis of staphylococcus aureus by macrophages exerts cytoprotective effects manifested by the upregulation of antiapoptotic factors. plos one. 2009;4(4):e5210. 8. zanoni i, granucci f. role of cd14 in host protection against infections and in metabolism regulation. front cell infect microbiol. 2013;3:32. 9. jacobsen m, repsilber d, gutschmidt a, et al. candidate biomarkers for discrimination between infection and disease caused by mycobacterium tuberculosis. j mol med (berl). 2007;85(6):613-21. 10. pallin dj, bry l, dwyer rc, et al. toward an objective diagnostic test for bacterial cellulitis. plos one. 2016;11(9):e0162947. skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 260 brief articles extensive palisaded neutrophilic granulomatous dermatitis with systemic lupus erythematosus luke j. maxfield, do1, laura s. tanner, md2, chelsea schwartz, bs3 1campbell university at sampson regional medical center, clinton, nc 2wilmington health, dermatology. associate professor of dermatology, campbell university, wilmington, nc 3lake erie college of osteopathic medicine, 20 seton hill dr, greensburg, pa palisaded neutrophilic granulomatous dermatitis (pngd) is a neutrophilic dermatosis associated with a characteristic phenotype of characteristic subcutaneous nodules overlying extensor surfaces, knuckles, and extremities.1 pngd may be seen in association with lymphoproliferative disorders, inflammatory bowel diseases, medications, and autoimmune connective tissue diseases. although rheumatoid arthritis is the most common underlying disease, systemic lupus erythematosus (sle) has also been encountered. we present a patient with known sle who developed multiple tender, violaceous, subcutaneous nodules, and was subsequently diagnosed with pngd. the patient reported allergy and intolerance certain first-line therapies, but oral corticosteroids led to the improvement of symptoms and over a period of months improvement of skin lesions. a middle-age african american woman was sent to our outpatient dermatology office through an internal referral from rheumatology within a large multidisciplinary private practice. the patient’s chief complaint was swollen red hands and case systemic lupus erythematosus (sle) is a multi-system disease with a myriad of mucocutaneous and systemic findings. one of the atypical cutaneous manifestations is palisaded neutrophilic granulomatous dermatitis (pngd). this uncommon condition presents as tender or asymptomatic, flesh-colored, red to violaceous subcutaneous nodules. the diagnosis may be suspected clinically but is confirmed by biopsy. the impact of the disease may be the direct result of pain, psychosocial, cosmetic concerns, or be the initial presentation of an underlying systemic disease. we present a patient with known sle who developed pngd. we also review similar clinical and microscopic disease entities with a summative comparison of neutrophilic dermatoses in patients with autoimmune connective tissue diseases. abstract introduction skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 261 generalized nodules that were progressing over a 7-month duration (figure 1). her medical history was significant for systemic lupus erythematosus, for which she was maintained on prednisone 5mg daily. physical exam revealed multiple erythematous, tender subcutaneous nodules involving primarily her thighs and forearms with additional lesions on her face and trunk. initial laboratory studies revealed serum complement c3, complement c4, antidsdna, creatine kinase, and erythrocyte sedimentation rate all within normal limits. a biopsy of a lesion revealed palisading histiocytes with lymphocytes and sparse neutrophils. stains were negative for increased mucin. clinical and histologic findings are consistent with palisaded neutrophilic and granulomatous dermatitis (pngd). figure 1. multiple dusky, erythematous, hyperpigmented nodules on the proximal right thigh when discussing treatment, the patient reported a severe allergy to hydroxychloroquine, as well as intolerance to dapsone, and was therefore prescribed oral prednisone 40mg daily for two weeks followed by a slow taper over two months while using topical clobetasol. along with initial symptomatic improvement, the patient's lesions stabilized with tapering of corticosteroids and continued to improve over a period of months. palisaded neutrophilic granulomatous dermatitis is a rare cutaneous condition. although the pathogenesis is not completely understood it is classically associated with underlying systemic disease. causes are multiple and include inflammatory bowel disease, infections, lymphoproliferative disorders, and most commonly, connective tissue diseases. also, medications such as ace inhibitors, diuretics, tumor necrosis factor-alpha inhibitors, and soy products may cause a similar clinical and histological presentation. pngd presents clinically as variably tender, symmetric, flesh-colored, erythematous to violaceous, umbilicated papules, nodules, and plaques that occur maximally on the extremities.1 most commonly, the elbows, knuckles, and knees are affected. histologically, early lesions of pngd reveal leukocytoclastic vasculitis with neutrophilic infiltrates throughout the dermis and late lesions reveal palisaded granulomas, collagen degeneration, neutrophilic debris, and eventually dermal fibrosis (figure 2).2-4 distinguishing the lesions of pngd from similar appearing clinical or histologic entities is essential. tumid lupus, erythema nodosum, and sweet’s syndrome may have a similar clinical appearance. the cutaneous lesions of lupus erythematosus tumidus appear as dermal, subcutaneous nodules, with little to no epidermal change. however, lupus erythematosus tumidus has a predilection for the face and trunk, and histopathology shows increased mucin.5 erythema nodosum classically presents as notably painful subcutaneous nodules. lesions of erythema nodosum are most discussion skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 262 figure 2. hematoxylin and eosin at 5x demonstrating palisading histiocytes with lymphocytes and sparse neutrophils commonly located on the legs and symmetric upper, and lower extremity involvement is unlikely. additionally, histopathology reveals prominent septal panniculitis with neutrophils admixed with eosinophils.6 sweet syndrome is a neutrophilic dermatosis associated with underlying infections, malignancy, or autoimmune conditions. sweet syndrome is heralded by the presence of fever, constitutional symptoms, and cutaneous lesions that present as painful vivid erythematous papules, nodules, and plaques. histologically a dense neutrophilic infiltrate without the presence of leukocytoclastic vasculitis is an additional major diagnostic criteria.7 granuloma annulare is more clinically distinct with localized or diffuse papules, nodules, or annular plaques with minimal epidermal change. granuloma annulare, however, may have similar-appearing histologic findings with an interstitial or palisading infiltrate, but unlike pngd, increased mucin is a prominent finding.8 the association of various neutrophilic dermatoses and underlying systemic diseases, infections, medications, and autoimmune conditions is extensive. neutrophic dermatoses associated with autoimmune conditions include sweet’s syndrome, pyoderma gangrenosum, rheumatoid neutrophilic dermatitis, neutrophilic panniculitis, subcorneal pustular dermatosis, erythema elevatum diutinum, and as demonstrated with our case, palisaded neutrophilic granulomatous dermatitis.10 the clinical features, associations, and histologic findings are summarized in table 1. when treating pngd, dapsone has demonstrated the greatest success, but cyclosporine, hydroxychloroquine, methotrexate, and prednisone are additional treatment options. if pngd is secondary to an underlying condition, treatment of the underlying disease may result in resolution of cutaneous findings. in patients with ulcerative colitis colchicine, minocycline, and high-potency topical steroids have shown improvement in patients with secondary pngd.3 pngd is a cutaneous manifestation of multiple underlying disease states but can be encountered in patients with lupus erythematosus. although the presence of pngd in patients with sle has an uncertain relationship to prognosis, may be associated with an increase in active lupus nephritis.9 additionally, the cutaneous lesions may be extensive be a source of great distress for patients. this case provides classic and histologic correlates as well as emphasizes a dermatologist’s role in the team-based healthcare model. conclusion skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 263 table 1. neutrophilic dermatoses and associated autoimmune and connective tissue diseases10 neutrophilic dermatoses clinical findings histopathologic findings associated systemic conditions palisaded neutrophilic granulomatous dermatitis • erythematous papules, plaques, and nodules • minimal tenderness sparse perivascular infiltrate with neutrophils, lymphocytes, and histiocytes ra sle ss ibd sweet’s syndrome • erythematous papules, plaques, and nodules • fever • malaise • neutrophilia • tender diffuse neutrophilic infiltrate papillary dermal edema minimal to absent leukocytoclastic vasculitis ra sle ibd pyoderma gangrenosum • ulcerative lesions with violaceous undermined borders non-specific sle ra juvenile ra ibd rheumatoid neutrophilic dermatitis • urticarial papules, plaques, and nodules • overlie joints • often symmetric dense neutrophilic infiltration of the dermis and may involve subcutis ra subcorneal pustular dermatosis • flaccid, annular, grouped pustules • involve trunk and intertriginous areas neutrophilic pustules in the upper epidermis ra sle sjo erythema elevatum diutinum • violaceous papules and nodules • extensor extremities leukocytoclastic vasculitis with mixed infiltrate ra neutrophilic urticaria (non-bullous neutrophilic dermatosis) • urticarial like lesions • pruritic • interstitial and perivascular neutrophilic infiltrate • leukocytoclasia • vacuolar interface dermatitis sle ra sjo abbreviations: ra; rheumatoid arthritis, sle; systemic lupus erythematosus, ss; systemic sclerosis, ibd; inflammatory bowel disease, sjo; sjögren syndrome skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 264 conflict of interest disclosures: none funding: none corresponding author: luke josiah maxfield, do campbell university at sampson regional medical center, dermatology wilmington health.1202 medical center dr, wilmington, nc 28403 phone: 719-201-3373 email: luke.maxfield@med.lecom.edu references: 1. hantash bm, chiang d, kohler s, florentino d. palisaded neutrophilic and granulomatous dermatitis associated with limited systemic sclerosis. j am acad dermatol. 2008;58(4): 661664. 2. kalen je, shokeen d, ramos-caro f, motaparthi k. palisaded neutrophilic granulomatous dermatitis: spectrum of histologic findings in a single patient. jaad case rep. 2017;3(5):425428. 3. hawryluk e, izikson l, english j. non-infectious granulomatous diseases of the skin and their associated systemic diseases. american journal of clinical dermatology. 2010;11(3):171-181 4. stiff km, cohen pr. palisaded granulomatous dermatitis associated with ulcerative colitis: a comprehensive literature review. cureus. 2017;9(1):e958. published 2017 jan 6. doi:10.7759/cureus.958 5. verma p, sharma s, yadav p, namdeo c, mahajan g. tumid lupus erythematosus: an intriguing dermatopathological connotation treated successfully with topical tacrolimus and hydroxyxhloroquine combination. indian j dermatol. 2014;59(2):210. doi:10.4103/00195154.127716 6. gupta p, saikia un, arora s, de d, radotra bd. panniculitis: a dermatopathologist's perspective and approach to diagnosis. indian j dermatopathol diagn dermatol 2016;3:29-41 7. cohen pr. sweet's syndrome--a comprehensive review of an acute febrile neutrophilic dermatosis. orphanet j rare dis 2007;2:34. 8. alirezaei p and farshchian m. granuloma annulare: relationship to diabetes mellitus, thyroid disorders and tuberculin skin test. clin cosmet investig dermatol 2017;10: 141-145. 9. terai s,. ueda-hayakawa, i., nguyen, c. t. h., ly, n. t. m. yamazaki, f., et al. palisaded neutrophilic and granulomatous dermatitis associated with systemic lupus erythematosus: possible involvement of cd163(+) m2 macrophages in two cases, and a review of published works. lupus 2018;27(14): 2220-2227. 10. bagherani n and smoller br. association of neutrophilic dermatoses with autoimmune connective tissue disorders: a real concept or an accident coincidence? glob dermatol 2016;3: doi: 10.15761/god.1000s1009 mailto:luke.maxfield@med.lecom.edu maintenance and improvement of skin clearance response with brodalumab among patients with moderate-to-severe psoriasis neal d. bhatia,1 seemal r. desai,2 craig teller,3 abby jacobson4 1therapeutics clinical research, san diego, ca; 2innovative dermatology, pa, plano, tx, the university of texas southwestern medical center, dallas, tx; 3bellaire dermatology, bellaire, tx; 4ortho dermatologics (a division of bausch health us, llc), bridgewater, nj 39th annual fall clinical dermatology conference® for dermatologists • october 17-20, 2019 • las vegas, nv introduction • brodalumab is a human anti–interleukin-17 receptor a monoclonal antibody that is efficacious in treating moderate-to-severe psoriasis1 • maintenance of skin clearance among patients receiving brodalumab 210 mg subcutaneously every 2 weeks (q2w) stratified by categories of psoriasis area and severity index (pasi) response at 12 weeks was previously assessed in two phase 3 studies (amagine-2/-3) of adults with moderateto-severe plaque psoriasis2 objective • to evaluate skin clearance response with brodalumab 210 mg q2w through week 52 in the phase 3, double-blind, randomized, placebocontrolled amagine-1 trial methods • patients in amagine-1 were initially randomized to brodalumab 210 mg q2w or placebo for 12 weeks3 • after 12 weeks, those receiving brodalumab 210 mg q2w who achieved static physician’s global assessment score of 0 or 1 (spga 0/1) were re-randomized to brodalumab 210 mg q2w or placebo • beginning at week 16, patients re-randomized to placebo who had return of disease, defined as spga ≥3, qualified for retreatment with their induction dose of brodalumab • 128 patients from amagine-1 who received continuous brodalumab 210 mg q2w through week 52 were included in this post hoc analysis comprising – 83 patients who were re-randomized to brodalumab 210 mg q2w – 45 non–re-randomized patients who received brodalumab 210 mg q2w after inadequate spga response • skin clearance was monitored by categories of pasi response using nonresponder imputation results week 12 pasi responses • at week 12, among 128 patients who received continuous brodalumab 210 mg q2w, 63% achieved pasi 90% improvement (pasi 90) or greater (37% achieved pasi 100 and 26% achieved pasi 90 to <100; table 1) pasi responses at weeks 16, 28, and 52 • among patients achieving pasi 100 at week 12, >75% maintained pasi 100 at weeks 16 and 28 – 81% maintained pasi 100 at week 16 – 77% maintained pasi 100 at week 28 • among patients achieving pasi 100 at week 12, 79% maintained pasi 100 through week 52 • notably, most patients (64%) who achieved pasi 90 to <100 at week 12 either improved to pasi 100 (49%) or maintained the same level of clearance (15%; figure 1) at week 52 • of patients who achieved pasi 75 to <90 at week 12, 43% experienced improvement at week 52 (19% improved to pasi 100 and 24% improved to pasi 90 to <100) acknowledgments: this study was sponsored by ortho dermatologics. medical writing support was provided by medthink scicom and funded by ortho dermatologics. ortho dermatologics is a division of bausch health us, llc. references: 1. siliq [package insert]. valeant pharmaceuticals north america llc; 2017. 2. strober et al. poster presented at: 76th annual meeting of the american academy of dermatology; february 16-20, 2018; san diego, ca. 3. papp et al. br j dermatol. 2016;175:273-286. © 2019. all rights reserved. table 1. pasi response at week 12 in amagine-1 3 6 9 15 49 18 responses at week 52 among week 12 pasi 90 to <100 responders, % pasi <50 pasi 50 to <75 pasi 75 to <90 pasi 90 to <100 pasi 100 othera among pasi 90 to <100 responders at week 12, most (64%) improved to pasi 100 (49%) or maintained the same level of response (15%) figure 1. pasi responses at week 52 among patients receiving brodalumab 210 mg q2w who achieved pasi 90 to <100 at week 12. pasi, psoriasis area and severity index; q2w, every 2 weeks. aother includes 6 patients who discontinued before week 52 (n=2), those who received retreatment after return of disease (static physician’s global assessment score ≥3) at or after week 16 (n=3), and those with missing data (n=1). conclusions • these data demonstrate maintenance and continued improvement of skin clearance through week 52 with brodalumab response at week 12, n (%) continuous brodalumab 210 mg q2w (n=128) pasi 100 47 (37) pasi 90 to <100 33 (26) pasi 75 to <90 21 (16) pasi 50 to <75 11 (9) pasi <50 16 (13) pasi, psoriasis area and severity index; q2w, every 2 weeks. skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 502 research letter biologic treatment of psoriasis and tuberculosis testing: a retrospective analysis emma batchelder, md1, mara trifoi, bs2, julie hong, bs2, steven maczuga, ms3, joslyn sciacca kirby, md, ms, med3 1 department of psychiatry, penn state health, hershey, pa 2 penn state college of medicine, hershey, pa 3 department of dermatology, penn state health, hershey, pa several biologic therapies are commonly used for the treatment of moderate-to-severe psoriasis1,2, including tumor necrosis factor (tnf)-α inhibitors. these treatments may increase the risk of reactivation of latent tuberculosis infection (ltbi) or active tuberculosis (tb) infection.3 while the unites states (us) has a low tb burden4, it is recommended that patients have a pretreatment test with discretionary testing thereafter for all but high-risk patients3. this abstract background: current recommendations for biologic use in psoriasis recommend baseline tb screening with igra. studies have found in low tb prevalence countries that tb conversion occurs at low rates in those utilizing biologic therapies. objectives: to evaluate utilization and cost effectiveness of tb testing in patients with psoriasis being treated with biologics. methods: we retrospectively queried a national commercial claims database (truven health marketscan) from 1/1/2014 to 12/31/2018 to investigate the use of tb screening and disease prevalence among patients with psoriasis being treated with a biologic agent. inclusion criteria consisted of psoriasis disease status, continuous utilization of a biologic for one year prior and three years after the first biologic claim; and no claims for tb within the year prior to starting the biologic. results: 3,421 patients with psoriasis and concurrent biologic treatment use were included in the study. 84.7% (2,897) had a baseline tb test within 15 months prior to first claim of biologic use. baseline tests were primarily igra (75.8%, n=2,195) with ppd tests only being used in 24.2% (n = 702) of patients. total cost for baseline tb test in the cohort amounts to $738,117. tb tests were positive in 4.1% (n = 147) of patients and tnfα inhibitors was the most frequently prescribed biologic. conclusions: the majority of patients diagnosed with psoriasis had a claim for baseline tb testing. current recommendations surrounding biologics and tb screening should take into account the high cost of baseline tb testing and the low rate of tb prevalence among patients on biologics. introduction skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 503 paper examines the utilization and cost of tb testing for us patients with psoriasis treated with biologics. a retrospective cohort study was conducted from 1/1/2014 to 12/31/2018 using the truven health marketscan commercial claims database (ann arbor, mi), which contains healthcare claims from approximately 350 payers in the us. inclusion criteria included psoriasis (1+ claims with international classification of diseases version [icd]-9: 696.1 or icd-10: l40.0/l40.1/l40.4/l40.8/l40.9), 1+ claims for one a biologic therapy including: etanercept, adalimumab, ustekinumab, brodalumab, certolizumab, guselkumab, infliximab, ixekizumab, or secukinumab; continuous enrollment for one year prior to and three years after the first biologic claim; and no claims for tb within the year prior to starting the biologic. demographic characteristics, tb diagnosis (ltbi: latent tb icd-9 795.51/795.52 icd-10 r76.11/r76.12; active tb: icd-9 10-18, icd-10 a15/a17/a18/a19) as well as frequency and costs for tb testing were extracted. common procedural terminology (cpt) codes were used to identify purified protein derivative (ppd) test and interferon gamma release assay (igra) claims (cpt 86580 and 86480/86481, respectively). costs were taken from the perspective of the health-system and were adjusted for inflation to 2020 us dollars (https://www.usinflationcalculator.com/). analyses were performed with sas version 9.4 (sas, cary, nc). overall, 3,421 patients with psoriasis and biologic treatment were included (table 1). of these, 84.7% (n=2,897) had a baseline tb test (within 15 months prior or three months after first claim for starting a biologic). the majority of baseline tests were igra (75.8%, n=2,195) with ppd accounting for 24.2% (n=702). annual testing was performed in the minority (18.0%, n=1034) and of these 92.9% (961/1034) received a tnf-inhibitor. the majority (96.7%, n=2,129) had less frequent testing (mean=9.22 (standard deviation [sd] 13.44)) months. repeat testing, defined as a second claim within 30 days, was performed for 1.3% (n=29). of these, the majority (27.6%, n=8) had a ppd as the first test and 72.4% (n=21) had an igra. the total cost of testing for the cohort was $738,117. tb tests were positive in 4.1% (n=147/3,559). most patients with a positive tb test had no biologic prescription within 30 days (53.6% [233/435])). for those prescribed a biologic, tnf-α inhibitor was most frequently prescribed, including etanercept (18.4% [42/228]), adalimumab (43.9% [100/228]), infliximab (1.3% [3/228]), or certolizumab (2.2% [5/228]) compared to other biologics including secukinumab (10.5% [24/228]) (table 2). the majority of people with psoriasis treated with a biologic did not have a claim for baseline tb testing. of those tested at baseline, the majority did not have subsequent annual testing. the rate of tb in the us is low5 and tb testing can be nonspecific, thus the value of routine widespread testing should be reconsidered. current recommendations do not require annual testing and suggest that patients be instead screened for symptoms and risk factors for tb.3 while guidelines recommend igra methods results discussion https://www.usinflationcalculator.com/ skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 504 table 1. sample characteristics (n=3,421) demographic n % sex male 1,655 48.38% female 1,766 51.62% age group 0-17 56 1.64% 18-34 363 10.61% 35-44 725 21.19% 45-54 1,092 31.92% 55-64 1,185 34.64% region northeast 620 18.12% north central 685 20.02% south 1,731 50.60% west 380 11.11% unknown 5 0.15% skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 505 table 2. tuberculosis testing utilization and costs n (%) cost* baseline tb test performed yes no 2,897 (84.7%) 344 (10.1%) total: $738,117 - baseline tb test type ppd igra 702 (24.2%) 2,195 (75.8%) total: $56.43 (29.57)^ testing frequency n (%) months between any tb test mean (sd) tested annually 72 (3.3%) 12.5 (1.2) tested at interval other than annually 2,129 (96.7%) 33.1 (48.1) tb diagnosis yes no age, mean (sd) 51.0 (9.9) 47.5 (11.9)** sex, male, n (%) (51.7%) (48.6%) months on biologic, mean (sd) 20.4 (11.3) 20.1 (11.7) *cost adjusted for inflation to 2020 us dollars ^mean (sd), median cost per test **p-value <.001 skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 506 rather than ppd, we found that igra was used infrequently.6 there are limitations to this study; clinical risk factors for tb were not examined and only patients with private insurance were included. overall, this data suggests that there is an opportunity to reevaluate the value of tb laboratory screening given these trends, the low tb infection rate in the us, and the cost and consequences of false-positive tests. conflict of interest disclosures: none funding: none corresponding author: joslyn s. kirby, md, ms, med, department of dermatology penn state health milton s. hershey medical center 500 university dr hershey, pa 17033 email: jkirby1@pennstatehealth.psu.edu references: 1. boehncke wh, schön mp. psoriasis. lancet. 2015;386(9997):983-994. 2. karataş toğral a, muştu koryürek ö, şahin m, bulut c, yağci s, ekşioğlu hm. association of clinical properties and compatibility of the quantiferon-tb gold in-tube test with the tuberculin skin test in patients with psoriasis. int j dermatol. 2016;55(6):629-633. 3. menter a, strober be, kaplan dh, et al. joint aad-npf guidelines of care for the management and treatment of psoriasis with biologics. j am acad dermatol. 2019;80(4):1029-1072. 4. global tuberculosis report 2019. in. geneva: world health organization 2019. 5. schmit km, wansaula z, pratt r, price sf, langer aj. tuberculosis united states, 2016. mmwr morb mortal wkly rep. 2017;66(11):289-294. 6. lewinsohn dm, leonard mk, lobue pa, et al. official american thoracic society/infectious diseases society of america/centers for disease control and prevention clinical practice guidelines: diagnosis of tuberculosis in adults and children. clin infect dis. 2017;64(2):111-115. review of efficacy, cost, and adherence of field therapies for actinic keratosis nathaniel lampley iii university of cincinnati college of medicine cincinnati, oh rachel rigo md department of dermatology weill cornell medicine new york, ny todd schlesinger md clinical research center of the carolinas charleston, sc anthony m. rossi md department of dermatology dermatology service weill cornell medicine department of medicine new york, ny memorial sloan kettering cancer center new york, ny synposis field therapy for actinic keratosis (ak) offers the benefit of treating both visible clinical lesions and subclinical atypia. the primary goal is to reduce the risk of progression to keratinocyte carcinoma. when choosing a field therapy for ak, physicians should consider both the effective cost (ec)—defined as the approximated cost to achieve 100% ak clearance in a single patient—and patient adherence to treatment. a literature search revealed that the effective cost of 5-fluorouracil (5-fu) and in-office photodynamic therapy (pdt) are similar. however, the effect of patient adherence on real-world efficacy and long-term ak clearance favors in-office pdt and shorter-term topical regimens. objective to compare efficacy, cost, and adherence of topical therapies and in-office pdt for ak. methods the authors searched pubmed, embase, web of science, and google scholar databases for articles on ak field therapy published between october 2020 and march 2021. the estimated cost of a given regimen was calculated as a projection of the per-unit cost multiplied by the number of units needed to complete the regimen. to calculate the total cost for pdt, the procedural cost was estimated from the average national medicare reimbursement rate (as of may 23rd, 2021) and was added to the cost of the photosensitizer per treatment. effective cost (ec) was calculated by dividing total cost (tc) by the clearance rate (cr), ec=tc/cr. results commonly prescribed and studied fda-approved topical field treatments are shown in table 1. only bf-200 ala 10% gel has been approved by the fda for field treatment and is thus included in this analysis. effective cost of 5-fu 4% cream ($541.16 – $801.72) is similar to that of pdt with aminolevulinic acid (ala) 10% gel ($593.14 – $870.58). however, total cost of 5-fu ranges from $433 (4% cream) to $1503 (0.5% cream), whereas total cost for a single round of pdt with 10% ala gel is $540. in addition, at-home topical therapies present significant barriers to compliance due to expected local skin reactions and long treatment regimens for many of these therapies, leading to potentially lower efficacy than is reported in clinical trials. this favors in-office pdt and shorter-term topical treatments. conclusion in-office 10% gel ala-pdt is a cost-effective alternative to topical therapies and offers comparable efficacy in field-directed treatment of ak. this study was investigator-initiated and funded by biofrontera inc. cost/regimen estimated using wholesale acquisition cost (wac) package prices and medicare coverage rates for may 2021. *average wholesale price. 5-fu = 5-fluorouracil; ala = 5-aminolevulinic acid; cpt – current procedural terminology; total cost = cost/regimen + cpt cost; effective cost = total cost/ak clearance rate. 1 tolak, hill dermaceuticals, stanford, fl 2 ameluz, biofrontera, woburn, ma 3 efudex, bausch health us, bridgewater, nj 4 aldara,valeant pharmaceuticals north america, bridgewater, nj 5 klisyri, almirall llc, malvern, pa 6 carac, bausch health us, bridgewater, nj 7 solaraze, pharmderm, melville, ny 8 zyclara, valeant pharmaceuticals north america, bridgewater, nj references 1. breuninger h et al. j dtsch dermatol ges. 2013;11 suppl 3:37–45, 39–47. 2. stratigos aj et al. eur j cancer. 2015;51:1989–2007. 3. porceddu sv et al. j clin oncol. 2018;36:1275–1283. 4. regeneron pharmaceuticals, inc. libtayo® (cemiplimab-rwlc) injection, for intravenous use [us prescribing information]; 2021. available at: https://www. accessdata.fda.gov/drugsatfda_docs/label/2021/761097s007lbl.pdf. accessed january 28, 2022. 5. health canada. libtayo® – notice of compliance with conditions – qualifying notice; 2019. available at: https://www.canada.ca/en/health-canada/services/ drugs-health-products/drug-products/notice-compliance/conditions/libtayonotice-compliance-conditions-218718.html. accessed january 28, 2022. 6. brazilian health authority – anvisa. libtayo (cemiplimab): new indication; 2021. available at: https://www.gov.br/anvisa/pt-br/assuntos/medicamentos/ novos-medicamentos-e-indicacoes/libtayo-cemiplimabe-nova-indicacao. accessed january 28, 2022. 7. ministry of health israel. the israeli drug registry – libtayo; 2019. available at: https://israeldrugs.health.gov.il/#!/meddetails/164%2099%20 36023%2000. accessed january 28, 2022. 8. regeneron pharmaceuticals, inc. libtayo® (cemiplimab) approved by the european commission as the first immunotherapy indicated for patients with advanced basal cell carcinoma; 2021. available at: https://www.prnewswire.com/news-releases/libtayo-cemiplimab approved-by-the-european-commission-as-the-first-immunotherapyindicated-for-patients-with-advanced-basal-cell-carcinoma 301319988.html. accessed january 28, 2022. 9. migden mr et al. n engl j med. 2018;379:341–351. 10. migden mr et al. lancet oncol. 2020;21:294–305. background cutaneous squamous cell carcinoma (cscc) • surgical resection is a standard treatment option for the management of cscc with a cure rate of >95%. some patients, however, have high risk of recurrence as assessed by immune status, primary disease stage, extent of nodal involvement, presence of extracapsular extension, and prior treatment.1,2 • postoperative radiation therapy is recommended for patients with high-risk features, but relapse with locoregional recurrence or distant metastases may still occur.3 cemiplimab • cemiplimab is an anti−programmed cell death-1 (pd-1) antibody approved in the us and europe for the treatment of patients with locally advanced or metastatic cscc who are not candidates for curative surgery or radiotherapy and is approved or under review by other health authorities.4–8 • results from the phase 1 (nct02383212) and phase 2 (nct02760498) trials of cemiplimab generally demonstrated a clinically meaningful activity and an acceptable safety profile in patients with advanced cscc consistent with other anti–pd-1 agents.9,10 • the c-post study evaluates the efficacy of cemiplimab as adjuvant therapy for patients with high-risk cscc following surgery and postoperative radiation. here, we present the most recent study protocol amendment. table 2. key exclusion criteria • squamous cell carcinoma arising from non-cutaneous sites (note: patients with parotid scc are not excluded if impression of the investigator is that it arose from primary cutaneous lesion) • concurrent malignancy other than localized cscc or history of malignancy other than localized cscc within 3 years of date of randomization, except for tumors with negligible risk of metastasis or death • hematologic malignancies except for patients with cll who have not required treatment within ≥6 months • history of solid organ transplant except corneal transplants cll, chronic lymphocytic leukemia; cscc, cutaneous squamous cell carcinoma; scc, squamous cell carcinoma. table 1. key inclusion criteria • ≥18 years old (in japan only: ≥21 years old) • resection of pathologically confirmed cscc, with macroscopic gross resection of all diseased area • high-risk cscc, defined by at least one of the categories presented in figure 2 • completion of postoperative radiation therapy (≥50 gy) within 2–10 weeks of randomization • ecog performance status of 0 or 1 • adequate hepatic, renal, and bone marrow function cscc, cutaneous squamous cell carcinoma; ecog, eastern cooperative oncology group. patient eligibility summary • patients with high-risk cscc often experience relapse with locoregional recurrence or distant metastases. there is an unmet need to reduce the risk of cscc recurrence in these patients after curative surgery or radiation. • the c-post study is evaluating the efficacy of cemiplimab as adjuvant therapy for patients with high-risk cscc after surgery and postoperative radiotherapy. • this study is once again open for enrollment following interruptions owing to the covid-19 pandemic. figure 1. c-post study design †cemiplimab after disease recurrence permitted if protocol-specified criteria are met. q3w, every 3 weeks; q6w, every 6 weeks; rt, radiation therapy. radiation therapy treatment plan analysis • post-operative radiation therapy (rt) is delivered following complete macroscopic resection of high-risk cscc of head and neck (hn) and non-hn sites, prior to enrollment and randomization into the study. some patients will enter the study after having received rt at sites that are not participating centers. • a minimum set of rt details will be collected on all patients in the case report forms. additionally, retrospective random rt treatment plan review will be performed on approximately 20% of study patients, including the first enrolled in each site whenever possible. this review will be performed by the trans tasman radiation oncology group (trog) radiation therapy treatment plan review committee (rttprc). • a checklist of the source data required for each selected case will be provided by the rttprc. this checklist can also be accessed via the trog website (www.trog.com.au). • intensity-modulated radiotherapy is preferable, particularly for hn sites, but all forms of rt including three-dimensional conformal radiotherapy and electron beam therapy are acceptable. acknowledgments editorial writing support was provided by sameen yousaf, phd, of prime, knutsford, uk, funded by regeneron pharmaceuticals, inc., and sanofi. disclosure danny rischin reports institutional research grant and funding from regeneron pharmaceuticals, inc., genentech, sanofi, kura oncology, roche, merck sharp & dohme, merck kgaa, bristol-myers squibb, and glaxosmithkline; uncompensated scientific committee and advisory board from merck sharp & dohme, regeneron pharmaceuticals, inc., sanofi, glaxosmithkline, and bristol-myers squibb; and travel and accommodation from merck sharp & dohme and glaxosmithkline. presented at winter clinical derm 2023, january 13–18, 2023 (encore of previous presentation at the european association of dermato oncology [eado] congress, april 21–23, 2022, rischin d et al.). reused with permission. c-post protocol update: a phase 3, randomized, double-blind study of adjuvant cemiplimab versus placebo post surgery and radiation therapy in patients with high-risk cutaneous squamous cell carcinoma danny rischin,1 daniel brungs,2 fiona day,3 hayden christie,4 vishal a patel,5 gerard adams,6 james estes jackson,7 maite de liz vassen schurmann,8 dmitry kirtbaya,9 thuzar m shin,10 christopher d hart,11 elizabeth stankevich,12 siyu li,12 israel lowy,12 hyunsil han,12 priscila gonçalves,12 matthew g fury,12 sandro v porceddu13 1department of medical oncology, peter maccallum cancer centre, melbourne, australia; 2illawarra cancer care centre, wollongong hospital, wollongong, australia; 3department of medical oncology, calvary mater newcastle, waratah, australia; 4cancer care centre hervey bay, urraween, australia; 5institute for patient-centered initiatives and health equity, george washington university school of medicine & health science, washington, dc, usa; 6genesis cancer care, bundaberg, australia; 7radiation oncology centers, gold coast, australia; 8animi oncology treatment unit, university planalto catarinense (uniplac), centro, lages, brazil; 9state budgetary institution of health oncology dispensary no. 2, krasnodar, russia; 10department of dermatology, hospital of the university of pennsylvania, perelman center for advanced medicine, philadelphia, pa, usa; 11st vincent’s hospital melbourne, fitzroy, australia; 12regeneron pharmaceuticals, inc., tarrytown, ny, usa; 13school of medicine, university of queensland, herston, australia, and the department of radiation oncology, princess alexandra hospital, woolloongabba, australia methods study design • c-post is a randomized, placebo-controlled, double-blind, multicenter phase 3 study comparing cemiplimab versus placebo as adjuvant therapy for patients with high-risk cscc after surgery and postoperative radiation (nct03969004). the revised study design is shown in figure 1. treatment the study consists of two parts: • part 1: randomized (1:1), double-blind, placebo-controlled. • part 2: optional open-label cemiplimab treatment (for patients who experience disease recurrence). outcome measures • primary endpoint: disease-free survival (dfs). • secondary endpoints: overall survival (os), freedom from locoregional and distant recurrence, cumulative occurrence of secondary primary tumors, and safety. • exploratory endpoints: pattern of failures, geographic variations in administration of postoperative radiation, health-related quality of life, molecular characterization of pretreatment tumor samples, and circulating tumor dna detection. surgery, with high-risk features on surgical pathology report completion of post-operative rt patient information cards informed consent and screening completion of rt within 2–10 weeks n=412 randomize 1:1 cemiplimab for up to 48 weeks: 350 mg q3w for 12 weeks, followed by 700 mg q6w for 36 additional weeks placebo for up to 48 weeks: q3w for 12 weeks, followed by q6w for 36 additional weeks primary endpoint: disease-free survival† figure 2. high-risk cscc features †defined as extension through the lymph node capsule into the surrounding connective tissue with or without associated stromal reaction. cscc, cutaneous squamous cell carcinoma; ece, extracapsular extension; hn, head and neck. high-risk cscc features *additional features: • ≥n2b disease associated with the recurrent lesion • nominal ≥t3 (recurrent lesion ≥4 cm in diameter or minor bone erosion or deep invasion >6 mm measured from the granular layer of normal adjacent epithelium) • poorly differentiated histology and ≥20 mm diameter of recurrent lesion. the recurrent lesion must be documented to be within the area of the previously resected cscc by radial measurement of the greatest radius of the final defect, measured from the estimated center of the original surgical wound recurrent cscc • cscc that arises within the area of the previously resected tumor, plus ≥1 additional feature* inclusion 3e perineural invasion • clinical and/or radiologic involvement of named nerves inclusion 3d t4 lesion • including hn and non-hn lesions inclusion 3c in-transit metastases • skin or subcutaneous metastases that are >2 cm from the primary lesion but are not beyond the regional nodal basin inclusion 3b nodal disease with ece† and ≥1 node ≥20 mm and/or ≥3 lymph nodes regardless of ece • per surgical pathology report inclusion 3a scan the qr code for co-author disclosures. microsoft word 3. 686 proof done.docx skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 15 in-depth reviews clinician-dermatopathologist communication via the requisition form in the era of electronic medical records: a review of the literature haley d. heibel, md,1 clay j. cockerell, md, mba2 1suny downstate health sciences university, brooklyn, ny, usa 2cockerell dermatopathology, dallas, tx, usa background: there are shortcomings in the quality and accuracy of clinical information on skin biopsy requisition forms (sbrfs). most sbrfs are completed via the electronic medical record (emr). this impacts workflow and the quality of submitted clinical information. an evaluation of clinician-dermatopathologist communication identified targets for improvement in this system. objective: to determine the impact of emrs on the handling of sbrfs by clinicians, identify barriers to effective clinician-dermatopathologist communication, and provide suggestions for improvement in this system. methods: a literature search was conducted on medline, cinahl, and scopus including the keywords of dermatology*, dermapatholog*, dermatopathology*, and requisition*. 20 articles were retrieved. 17 articles were included from this search and from cross-referencing articles. results: this review reaffirmed the inadequacy of clinical information provided to dermatopathologists. standardization of and formal education in completing sbrfs, along with dermatopathologist access to information and images via shared emr may improve histopathologic interpretation of specimens and allow for cost-effective patient care. limitations: this review was restricted to the english language. previous study designs have primarily been retrospective and surveys. conclusion: the development of user-friendly standardized sbrfs with validated criteria are necessary. clinicians must learn to convey information on the sbrf using appropriate terminology in ways that enhance the workflow of both clinicians and dermatopathologists and improves patient outcomes. abstract skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 16 in dermatology, the skin biopsy is an important part of the clinical evaluation, and the skin biopsy requisition form (sbrf) is the primary and critical method of communication between the clinician and the pathologist.1,2 the quality, completeness, and accuracy of the clinical information on the sbrf influences the dermatopathologist’s ability to make an accurate and timely histopathologic diagnosis, clinically meaningful histologic interpretation, and appropriate treatment recommendations for the clinician.2-4 previous research regarding clinicpathological consistency has suggested the clinical diagnostic accuracy rates of dermatologists were significantly higher than physicians of other disciplines.3,5 despite the comparative higher accuracy of clinical diagnoses on sbrfs by dermatologists, data has demonstrated that the ideal amount and quality of information on sbrfs for histopathological interpretation is often incomplete or absent and impedes the ability of dermatopathologists to make an accurate and efficient diagnostic decision.1,6,7 an increasing number of sbrfs are completed electronically because many practices have adopted electronic medical records (emr). requisition form completion through emr portals has led to improvements in labeling and processing of skin biopsy specimens and virtually eliminated lost sbrfs.4 however, since the advent of emr, dermatopathologists have anecdotally reported an unfavorable impact on the quality of clinical information obtained from the sbrf. the purpose of this study is to document deficiencies in the handling of sbrfs by dermatologists in the context of the emr and suggest opportunities for improvement. barriers to effective cliniciandermatopathologist communication clinicians’ workflow and beliefs. current barriers to the provision of necessary and pertinent clinical information on the sbrf by clinicians include: high patient volumes, time constraints of clinic visits, lack of knowledge of the important role that clinical information has for an accurate histopathologic interpretation, the level of dermatologic experience of the submitting physician, the quality of skin biopsy specimens, lack of consensus of what clinical information should be included on the sbrf, and completion of the sbrf by health care staff other than the physician with varying levels of dermatologic experience.4,6,8-10 another contributing factor to the dearth of clinical information on sbrfs may be the open-ended structure of many sbrfs that does not encourage clinicians to state specific clinical information (fig. 1).9 specific challenges related to emr requisitions. in an audit of sbrfs, kinonen et al11 found that there were more data entry errors on requisitions completed via emr (3.9% of sbrfs) than handwritten requisitions (3.0% of sbrfs). the most common source of error for both handwritten and electronically generated sbrfs was container labeling. the most frequent container labeling errors were an absence of the procedure site or a discrepancy between the procedure site written on the sbrf and the container. an interesting finding was that there was a larger proportion of errors related to container labeling from the emr, with 109/113 errors (96%) being related to container labeling, than those generated by handwritten process (207/258, 80%). the prominence of container labeling errors from labels generated by emr in this study may introduction discussion skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 17 be accounted for by the requirement for the procedure site to be handwritten on the container label containing printed patient information. some electronic sbrfs automatically generate textbook descriptions of clinical morphology based on the clinical diagnosis provided. for example, a clinician may take a biopsy of a psoriatic lesion, and the emr automatically enters a description that states, “psoriasiform plaques with micaceous scale” (fig. 2). however, this clinical information is not helpful because a biopsy of a characteristic lesion of psoriasis would not be necessary, and it may not accurately describe the patient’s presentation. we have also received a sbrf that did not match the figure 1. this sbrf does not indicate clinical history or impression. figure 2. an automatically generated clinical description of a classical lesion of psoriasis. a lesion with this morphology would not require biopsy. figure 3. this clinician manually provided clinical history on this electronic sbrf of an inflammatory lesion. skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 18 specimen because the electronic sbrf was a re-populated description of a previous biopsy. these features that seem to make the emr more user-friendly may mislead dermatopathologists to an erroneous diagnosis. many inflammatory skin diseases have clinical presentations that are more complex than any automatically generated description would provide, and it is cumbersome and difficult for clinicians to enter information into specific fields in the emr template (fig. 3). additionally, some phrases are automatically accompanied with certain biopsies, which may not be relevant to clinicians’ concerns. for example, many cyst biopsies automatically generate the phrase “please check margins,” which may lead to increased costs, technician time, and resources if the dermatologist does not eliminate the phrase. effects on dermatopathologists. dermatopathologists have reported that a common problem in their practice is insufficient clinical information regarding skin biopsy specimens.10 other barriers for dermatopathologists in achieving effective communication with clinicians include situations with limited access to a shared emr to review pertinent clinical information and limitations in giving feedback to clinicians to encourage better communication via the sbrf due to concern of losing business in the private setting.10 when dermatopathologists have provided feedback to clinicians directly or via the pathology report to address specimen inadequacies, clinicians who obtain small biopsy specimens were generally not responsive.2 comfere et al6 found in a systematic review that clinical information and a differential diagnosis were provided in only 36% (18 of 50 dermatologists) of sbrfs with considerable variation in the content of sbrfs. use of nonspecific terminology on the sbrf, such as “rule out”, may be associated with diagnostic delays and the use of unnecessary pathology services including higher rates of stain utilization and more sections in a non-integrated (external cases) practice but not in an integrated (internal cases) practice of a single dermatopathology group.12 however, dermatopathologists reported in a survey significant dissatisfaction with time spent gathering information necessary for an accurate and timely diagnosis with 44.7% (261/584) reporting an average of 30 minutes or more daily searching for clinical information to facilitate in histopathologic examination.2,7 they noted that there were advantages to access of clinical information via emr, but there were associated obstacles of increased time and effort to identify pertinent clinical information.2 with increasing use of template notes consisting of pre-filled phrases and check boxes, the clinical narratives containing useful descriptions for histopathologic interpretation are less common.2,8 in a retrospective review of sbrfs and associated encounter visit notes (evns), olson et al4 found that missing critical information on the sbrf was often present in the evn, but that some important clinical information was absent from both sources. the lack of standardization of the format and clinical content of evns may account for inconsistent placement of information in various sections and the omission of important clinical information within evns.8 therefore, dermatopathologists may invest extensive time in the review of patient records without finding the necessary information for histopathologic interpretation. skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 19 recommendations for improvement education. communication and sharing of perspectives regarding the meaning of nonspecific terms on the sbrf may increase awareness of the implications that nonspecific terms such as “rule out” have on the workflow and utilization of resources by the pathologist and may represent another approach to enhance histologic interpretation of skin biopsies.12 dermatopathologists have proposed educating dermatology and nondermatology trainees and clinicians about the importance of complete and accurate clinical information on the sbrf through periodic inoffice tutorials, case-based feedback on the dermatopathology report, and structured curriculums in residency regarding the role that clinical information has on accurate histopathologic interpretation and appropriate specimen and clinical photography obtainment.10 changes in work environment. with increased physician extenders and nondermatologists providing dermatologic care, efforts may be focused on optimizing the work environment for dermatologists to complete all sbrfs and on educating physician extenders and non-dermatologists how to provide complete, relevant, and accurate clinical information and specimens for histopathologic examination.10 ideally, the sbrf should be completed by the dermatologist who obtains and submits the specimen.5 requisitions generated by emr overcome some of the limitations of handwritten sbrfs including discrepancies between demographics on the patient chart and the sbrf, incomplete patient demographics, the lack of indication of the requesting physician, and illegible sbrfs.11 requisition forms generated by emr may be improved by entirely linking the emr data entry to the sbrf to include patient demographics, date, and procedure site and processes to promote proper label usage.11 direct transfer of relevant clinical data from the evn to the sbrf may overcome the error prone and inefficient requirement for duplicated data entry for both the evn and the sbrf in some current emrs that may account for frequent discrepancies between the evn and sbrf.8 however, the sbrf may evolve into a duplicate of the evn and be undervalued in the setting of an integrated emr and access to clinical images.8 standardization of the organization of the evn regarding important clinical information may enhance dermatopathologists’ efficiency in finding pertinent information and the accuracy of histopathologic interpretation.4 standardization of the sbrf. communication between clinicians and dermatopathologists may be improved through institution of standards for sbrfs by professional groups, required clinical elements on the sbrf, and the development of a consistent and efficient system to collect, deliver, and communicate clinical information to dermatopathologists.10 electronic sbrfs may be improved by the inclusion of checklists with required fields and clear descriptions to allow for greater ease in extracting information by the dermatopathologist.10 after the implementation of templated electronic sbrfs, maley et al13 found an increased amount of pertinent clinical information on the sbrf for specimens with a final diagnosis of melanoma and that electronic sbrfs were significantly more likely than handwritten sbrfs to include the type of biopsy specimen, a larger number of differential diagnoses, a recorded diameter of the lesion, and a greater proportion of the lesion removed in the biopsy specimen. skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 20 although standardized definitions and the diagnostic utility of critical clinical entities on the sbrf have not been extensively studied, dermatopathologist respondents of a survey have reported the clinical diagnosis provided by the dermatologist to be the most important component on the sbrf.6,10 this is confirmed by a retrospective study of 3,949 pathological reports by aslan et al3 who found that sufficient clinical descriptive knowledge increases the probability of an accurate diagnosis. description of clinical morphology is beneficial for the dermatopathologist when clinical diagnosis on the sbrf does not correlate with histopathologic interpretation.10 use of specific terminology on the sbrf. sellheyer and bergfeld5 recommended a specific clinical diagnosis and a differential diagnosis to be included on the sbrf and discouraged the use of obscure abbreviations, “rule out,” and vague terminology such as “lesion,” “skin rash,” “recent changes,” and “skin anomaly.” dai et al14 found in a retrospective study of sbrfs of inflammatory skin diseases that, when a single diagnosis was listed, the term rule out often accompanied the diagnosis. the physician’s intent was to confirm the diagnosis, making the use of the term “rule out” misleading.14 they recommend using the word “likely” or “suggest” instead. other vague terminology is not helpful for clinicopathological correlation without additional clarification, may prompt orders for deeper sections and special stains, and may delay the final report.5 for inflammatory skin diseases, inclusion of only a clinical diagnosis may not be sufficient and may influence the dermatopathologist to focus on histopathologic features consistent with the clinical diagnosis when the specimen represents another diagnosis.5,8 however, the presence and accuracy of the clinical impression of inflammatory lesions is the most critical of all clinical entities on the sbrf.8 supplemental clinical images. dermatopathologists have reported that clinical photographs are valuable and may be sufficient clinical information when a clinical description is lacking.2 when information on the sbrf is ambiguous or absent, the inclusion of clinical and dermoscopic images on the sbrf may establish a more complete understanding of the clinical presentation for the pathologist.15 in busy dermatology practices, applications that allow for easy and direct upload of clinical images into emr have enhanced efficiency.2 the inclusion of images with the sbrf may enhance histopathologic interpretation, but should only be considered as a supplement and not a replacement for clinical information.5 dermoscopic findings may serve as an ideal communication bridge between clinicians and dermatopathologists because many dermoscopic features have direct histopathologic correlates and dermoscopy can be used in vivo and on excised tissue after formalin fixation.15,16 dermoscopy provides an innovative approach for clinicians to make clinical decisions and to share their thought processes regarding diagnosis and patient management.16 this may enhance clinician-dermatopathologist communication through improvements in clinicians’ diagnostic accuracy and in appropriateness of skin biopsy specimens and will result in optimized histopathologic interpretation by dermatopathologists.16 features of the clinician dermatopathologist communication loop. clinical and pathology practices that are in close proximity may allow for ease and efficiency of face-to-face communication and shared decision making between clinicians skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 21 and dermatopathologists.2 this allows for joint clinician-dermatopathologist examination to acquire relevant clinical information, to examine the “gross” pathology, and to encourage case discussion.2,4 in addition, dermatopathologists who rely on face-to-face communication spend less time on average (< 30 minutes) daily searching for clinical information than those who rely on telephone or sbrfs.2 this review has explored how knowledge gaps of clinicians regarding the importance of pertinent clinical information for accurate histopathologic interpretation and characteristics of the work environment and format of electronic sbrfs may affect the completion of sbrfs in the context of emr. for improvements in computerized data entry, standardization of the sbrf and associated evn is necessary and should be user-friendly and easily integrated into the current workflow of practices.4 emr programming companies should additionally provide resources and formal training in using the program. an electronic system would be valuable that allows the clinician to efficiently search for relevant clinical note fields, enter data, and present information that is well organized for the dermatopathologist.4,10 the use of criteria to assess for completeness and accuracy of sbrfs has not been validated.17 a consensus of standardized definitions of critical clinical elements on the sbrf and their diagnostic utility is necessary.6 efforts designed to categorize and develop a tier-based system of useful clinical information and indications for clinical photographs based on the clinical diagnosis and presentation would benefit both clinicians and dermatopathologists. efforts to identify and close a knowledge gap of the medicolegal importance of the sbrf may prompt a change in practices of the completion of sbrfs. data from a survey study indicated that most dermatologists are aware that the sbrf is part of the permanent medical record, but over 50% of the time these forms are not personally completed or checked for accuracy.18 our goal is to raise awareness of the changes introduced in clinician-dermatopathologist communication in the era of emr to encourage behavior change in dermatologists’ practices in completing sbrfs. abbreviations used: sbrf (skin biopsy requisition form), emr (electronic medical record), evn (encounter visit note) key words: dermatopathology; skin biopsy; requisition form; electronic medical records; communication; review conflict of interest disclosures: none funding: none corresponding author: haley d. heibel 461 dean street unit 30a brooklyn, ny 11217 phone number: (402)-525-0134 email: haley.heibel@downstate.edu references: 1. chismar la, umanoff n, murphy b, viola kv, amin b. the dermatopathology requisition form: attitudes and practices of dermatologists. j am acad dermatol. 2015;72(2):353-355. 2. comfere ni, peters ms, jenkins s, lackore k, yost k, tilburt j. dermatopathologists' concerns and challenges with clinical information in the skin biopsy requisition form: a mixed-methods study. j cutan pathol. 2015;42(5):333-345. conclusion skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 22 3. aslan c, göktay f, mansur at, aydingöz ie, günes p, ekmekçi tr. clinicopathological consistency in skin disorders: a retrospective study of 3949 pathological reports. j am acad dermatol. 2012;66(3):393-400. 4. olson ma, lohse cm, comfere ni. rates of provision of clinical information in the skin biopsy requisition form and corresponding encounter visit note. j pathol inform. 2016;7:40-40. 5. sellheyer k, bergfeld wf. "lesion," "rule out...," and other vagaries of filling out pathology requisition forms. j am acad dermatol. 2005;52(5):914-915. 6. comfere ni, sokumbi o, montori vm, et al. provider-to-provider communication in dermatology and implications of missing clinical information in skin biopsy requisition forms: a systematic review. int j dermatol. 2014;53(5):549557. 7. trotter mj, au s, naert ka. practical strategies to improve the clinical utility of the dermatopathology report. arch pathol lab med. 2016;140(8):759765. 8. romano rc, novotny pj, sloan ja, comfere ni. measures of completeness and accuracy of clinical information in skin biopsy requisition forms: an analysis of 249 cases. am j clin pathol. 2016;146(6):727-735. 9. waller jm, zedek dc. how informative are dermatopathology requisition forms completed by dermatologists? a review of the clinical information provided for 100 consecutive melanocytic lesions. j am acad dermatol. 2010;62(2):257-261. 10. wong c, peters m, tilburt j, comfere n. dermatopathologists' opinions about the quality of clinical information in the skin biopsy requisition form and the skin biopsy care process: a semiqualitative assessment. am j clin pathol. 2015;143(4):593-597. 11. kinonen cl, watkin wg, gleason bc, johnson cej, thomas ab, cibull tl. an audit of dermatopathology requisitions: hand written vs. electronic medical record data entry accuracy. j cutan pathol. 2012;39(9):850-852. 12. abdou y, lohse c, comfere ni. use of the term "rule out" in requisition forms may cause diagnostic delays in dermatopathology practice. int j dermatol. 2017;56(1):86-91. 13. maley a, swerlick r, stoff b. comparison of electronic and handwritten pathology requisition forms for cutaneous melanoma. j am acad dermatol. 2015;72(5):916-917. 14. dai h, machan m, fraga gr. how accurate are the suggested diagnoses on biopsy requisitions for inflammatory skin disease? a retrospective study of 348 cases. am j dermatopathol. 2014;36(4):298-302. 15. yelamos o, braun rp, liopyris k, et al. usefulness of dermoscopy to improve the clinical and histopathologic diagnosis of skin cancers. j am acad dermatol. 2019;80(2):365-377. 16. yélamos o, braun rp, liopyris k, et al. dermoscopy and dermatopathology correlates of cutaneous neoplasms. j am acad dermatol. 2019;80(2):341-363. 17. zohar y, shreberk-hassidim r, elia j, et al. clinical description of skin lesions in pathology requisition forms completed by plastic surgeons is lacking: a retrospective study of 499 lesions. eur j plast surg. 2018;41(2):249-252. 18. heibel, hd, brown, me, davis, tl. a survey of dermatologists’ practices in completing the skin biopsy requisition form in the era of electronic medical records. poster presented at: texas dermatological society annual spring meeting; may 17-18, 2019; houston, tx. s. seite, d. moyal la roche-posay dermatological laboratories, asnières, france introduction methods observational study on patients with acne and at risk of post-inflammatory hyperpigmented lesions acne is one of the major reasons for dermatological consultation. post-inflammatory hyperpigmentation (pih) is sometimes associated with inflammatory lesions. the aim of this observational study was to evaluate the use of a topical formula containing ingredients (niacinamide, procerad, lha, piroctone olamine, linoleic acid) to reduce acne lesions and pih, alone or in adjunctive therapy, in patients with mild to moderate acne and post-inflammatory hyperpigmented lesions. this survey included 5232 patients (68.2% female, 31.8% male; mean age 22.9 ± 7 years old) with mild (47.9%) to moderate (47.4%) acne and was conducted by private practice dermatologists. phototypes of patients were distributed as 6.7% phototype i, 47.5% phototype ii, 38.9% phototype iii, and 6.5% phototype iv. 75.8% of patients showed residual colored marks on the face. at baseline, the dermatologists completed a questionnaire concerning the patient profile, an evaluation of clinical acne severity (gea) and noted the treatment regimen prescribed. at the second visit, planned 2 months later, dermatologists re-evaluated the acne severity, overall tolerance, reduction of seborrhea and residual colored marks. the topical skin care product was applied twice a day for 53% of patients, in the morning for 31.7% and in the evening for 15.3%. some patients used the topical skin care product alone (35.6% of patients) and others used with the same product in adjunctive therapy (64.4% of patients). results conclusion this survey demonstrated that a dermocosmetic product containing lipohydroxy acid, salicylic acid, linoleic acid, niacinamide, piroctone olamine and procerad (anti-inflammatory and anti-melanin synthesis action) can provide good results in managing acne patients with risks of post-inflammatory hyperpigmented lesions,when associated with therapeutic treatments or alone for milder acne. 80.1% of patients presented an improvement of their acne showing a significant effect (p<0.0001) of the skin care product after 2 months. a significant (p< 0.0001) decrease (-47.3% on average) of seborrhea was observed after 2 months with improvement in 88.4% of patients. there was a significant decrease (p<0.0001) of the number of patients presenting marks at the end of the study. skin care product in monotherapy severity of acne (gea) seborrhea evolution 10 ▲ ▼ 9 8 7 6 5 4 3 2 1 0 initial visit final visit l ev el o f se b o rr h ea 4.9 ± 2.1 2.6 ± 1.6 -47,3% 60% 50% 40% 30% 20% 10% 0% initial visit final visit % o f su b je ct s 8,5 0 36,4 47,9 6,6 0,6 11,1 40,6 39,3 8,3 0,6 0 mild severe moderate virtually no lesions very severe no lesions type of local treatments type of systemic treatments 20% 15% 10% 5% 0% % o f su b je ct s residual colored marks on the face there was a significant decrease (p<0.0001) of the number of patients presenting marks at the end of the study. skin care product in adjunctive therapy 17,2 59.4% of the patients had a local treatment and 19.9% a systemic treatment. 83% of patients presented an improvement of their acne showing a significant effect (p<0.0001) of the treatment associated with the skin care product after 2 months. a significant (p<0.0001) decrease (-47.3% on average) of seborrhea was observed after 2 months with improvement in 91.6% of patients. ▼ 10 ▲ 9 8 7 6 5 4 3 2 1 0 initial visit final visit l ev el o f se b o rr h ea 4.7 ± 2.1 2.4 ± 1.6 -47,3% 50% 40% 30% 20% 10% 0% final visitinitial visit % o f su b je ct s 15,3 0 36,8 43,1 4,4 0,4 17,6 44,2 32 5,8 0,4 0 mild severe moderate virtually no lesions very severe no lesions po b + ad ap ale ne as so cia tio n er yth rom yci n + tre tin oin as so cia tio n an tib iot ics az ela ic a cid re tin oid s po b ot he r lo ca l tr ea tm en t 15,5 11,8 9,5 7,1 3,3 6 10% 8% 6% 4% 2% 0% % o f su b je ct s 7,8 ho rm on al co ntr ace pti oncy cli ns an ti-a nd rog en s zin c g luc on ate ot he r s yst em ic tre atm en t 4,1 1,5 4,2 severity of acne (gea) seborrhea evolution the skin care product tolerance was evaluated by the dermatologists as high to excellent for 91.2% of the patients. 91.1% of the patients were satisfied to very satisfied by the product. 4,5 100% 80% 60% 40% 20% 0% initial visit final visit % o f su b je ct s no residual colored marks on the face residual colored marks on the face 76,1 23,9 56,4 43,6 residual colored marks on the face 100% 80% 60% 40% 20% 0% initial visit final visit % o f su b je ct s no residual colored marks on the face residual colored marks on the face 83,6 16,4 66,1 33,9 fc17posterlarocheseiteacneandlesions.pdf patients’ quality of life in a phase 4 real-world study of tildrakizumab in moderate-to-severe plaque psoriasis jayme heim1, j gabriel vasquez1, brad schenkel2, neal bhatia3 1west michigan dermatology, grandville, mi, usa; 2sun pharmaceutical industries, inc., princeton, nj, usa; 3therapeutics clinical research, san diego, ca, usa introduction • psoriasis is a chronic, systemic, inflammatory disorder characterized by scaly, erythematous plaques on the skin that can significantly impact patients’ emotional and psychological well-being1 • tildrakizumab is an anti–interleukin-23 p19 monoclonal antibody approved for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy1,2 • efficacy of tildrakizumab for clinical improvement was associated with better skinrelated quality of life in the phase 3 resurface 1 and resurface 2 trials,3 but there is limited available real-world evidence regarding overall health-related quality of life (hrqol) in patients with moderate-to-severe plaque psoriasis objective • to evaluate improvement in general and skin-specific hrqol in patients with moderate-to-severe plaque psoriasis after 64 weeks of treatment with tildrakizumab under real-world conditions methods study design and population • this was a phase 4, 64-week, uncontrolled, open-label, real-world study (figure 1) figure 1. study design uncontrolled, open-label, single-arm, multicenter study (nct03718299) treatment and follow-up screening (n = 60) enrollment (n = 55) key criteria inclusion • male or female • ≥18 years • moderate-to-severe plaque psoriasisa • candidates for phototherapy or systemic therapy • no active or untreated latent tuberculosis exclusion • erythrodermic psoriasis • only pustular, guttate, or inverse psoriasis • other skin conditions that could interfere with evaluation screening and enrollment study visit injection screening x week: 0/baseline x x 4 x x 8 x 12 x 16 x x 20 24 28 x x 32 36 40 x x 44 48 52 x x treatment • tildrakizumab 100 mg administered at weeks 0 (baseline), 4, 16, 28, 40, and 52 • administered by a healthcare provider hrqol evaluation (itt population, n = 55) primary endpoint change from baseline in: • pgwbi total score at weeks 28 and 52 secondary endpoints change from baseline over time in: • pgwbi total and subscaleb scores • dlqi score proportion of patients with: • dlqi score of 0 or 1 • dlqi score ≤5 • ≥5-point reduction in dlqi score 64 x time points (weeks) shown in bold indicate when the primary efficacy endpoint was assessed (at weeks 28 and 52) and the end of the study (at week 64). absa ≥3%. bsubscales of anxiety, depressed mood, positive well-being, self-control, general health, and vitality. bsa, body surface area; dlqi, dermatology life quality index; hrqol, health-related quality of life; itt, intention-to-treat; pgwbi, psychological general well-being index. assessments • quality of life was evaluated using — the psychological general well-being index (pgwbi), administered at baseline and all postbaseline visits ○ total score is the sum of 6 subscale scores ○ higher pgwbi scores indicate improvement — the dermatology life quality index (dlqi), administered at baseline and all postbaseline visits ○ higher dlqi scores indicate greater impairment statistical analysis • the intention-to-treat population was used for quality-of-life analyses and included all patients who enrolled and were assigned to receive tildrakizumab • changes from baseline in pgwbi and dlqi scores were analyzed using student’s t-tests — missing data were not imputed results patient demographics • of 55 patients enrolled, 45 were assessed at week 64 (end of study) • the majority of patients were male (28/55; 50.9%) and white (52/55; 94.5%), with a mean ± standard deviation (sd) age of 48.6 ± 15.3 years (table 1) table 1. demographics and baseline characteristics characteristic tildrakizumab(n = 55) sex female 27 (49.1) male 28 (50.9) race white 52 (94.5) black or african american 2 (3.6) asian 1 (1.8) ethnicity hispanic or latino 5 (9.1) not hispanic or latino 50 (90.9) age, years, mean ± sd 48.6 ± 15.3 pgwbi score, mean ± sd total score 78.1 ± 14.1 positive well-being 12.6 ± 3.3 general health 9.9 ± 2.5 anxiety 16.9 ± 4.0 depressed mood 12.5 ± 2.1 self-control 12.9 ± 2.1 vitality 13.3 ± 3.2 dlqi score, mean ± sd 9.4 ± 5.2 itt population. data shown as n (%) unless otherwise noted. pgwbi, psychological general well-being index; dlqi, dermatology life quality index; itt, intention-to-treat; sd, standard deviation. improvement in pgwbi • the total pgwbi score improved significantly from baseline to week 64, with a mean ± sd change from baseline of 5.6 ± 14.1 (p = 0.01); the change from baseline was significant at both of the primary endpoint time points at week 28 (p = 0.033) and week 52 (p <0.001; figure 2) figure 2. mean pgwbi total and subscale scores through week 64 bl 4 8 12 16 28 40 52 64 0 10 20 30 40 50 60 70 80 90 100 week m ea n ± s d positive well-being general health anxiety depressed mood self-control vitality 78.1 (14.1) 82.3 (13.1) p = 0.004 82.8 (13.2) p = 0.016 82.7 (12.2) p = 0.018 83.5 (13.3) p = 0.005 82.2 (12.9) p = 0.033 83.3 (11.1) p = 0.003 85.2 (12.0) p <0.001 83.2 (13.5)p = 0.011 n = 55 55 53 54 54 53 48 48 45 16.9 (4.0) 17.9 (4.1) 17.9 (4.3) 18.1 (3.8) 18.0 (4.2) 17.8 (3.8) 18.1 (3.7) 18.3 (3.5) 18.0 (3.9) 12.5 (2.1) 13.1 (1.9) 12.8 (2.0) 13.1 (1.7) 13.0 (1.9) 12.5 (2.3) 13.1 (1.6) 13.0 (1.6) 12.7 (1.9) 12.6 (3.3) 13.3 (3.3) 13.8 (3.2) 14.0 (3.1) 14.0 (2.6) 13.6 (3.0) 13.7 (2.9) 14.4 (3.2) 13.8 (3.2) 12.9 (2.1) 13.0 (1.9) 13.2 (1.8) 13.0 (1.8) 13.2 (1.9) 13.0 (2.0) 13.4 (1.4) 13.4 (1.4) 13.2 (1.8) 9.9 (2.5) 10.9 (2.1) 11.5 (2.1) 10.9 (2.4) 11.4 (2.4) 11.5 (2.0) 11.1 (2.3) 11.8 (2.3) 11.5 (2.2) 13.3 (3.2) 14.2 (3.1) 13.6 (3.2) 13.5 (3.1) 13.9 (3.3) 13.9 (3.2) 14.0 (2.8) 14.3 (3.1) 14.0 (3.5) itt population. data labels report the mean (sd). p-values are for change from baseline based on student’s t-test. bl, baseline; itt, intention-to-treat; pgwbi, psychological general well-being index; sd, standard deviation. • the pgwbi components with significant improvement from baseline to week 64 were positive well-being (mean ± sd change, 1.4 ± 3.3; p = 0.008) and general health (mean ± sd change, 1.7 ± 2.3; p <0.001) • the mean ± sd change from baseline to week 64 for other pgwbi component scores was 1.1 ± 4.0 (p = 0.08) for anxiety, 0.4 ± 2.5 (p = 0.3) for depressed mood, 0.2 ± 2.1 (p = 0.5) for self-control, and 0.9 ± 3.2 (p = 0.06) for vitality improvement in dlqi • there were statistically significant improvements from baseline in dlqi score at all visits, beginning as early as week 4 with sustained improvement through week 64 • the dlqi score (mean ± sd) improved from 9.4 ± 5.2 at baseline to 2.0 ± 2.6 at week 64 (p <0.001; figure 3) figure 3. mean dlqi score through week 64 0 5 10 15 week 4 8 12 16 40 64 3.3* 2.9* 2.6* 2.0* 1.8* n = 55 52 52 54 48 45 2.2* 1.7* 28 52 4853 bl 55 5.5* 9.4 m ea n ± s d itt population. error bars represent the sd. *p <0.01. statistically significant change from baseline based on student’s t-test. bl, baseline; dlqi, dermatology life quality index; itt, intention-to-treat; sd, standard deviation. • proportions of patients meeting prespecified dlqi response thresholds at week 64 included — dlqi score of 0 or 1 signifying no negative impact on patients’ quality of life: 62.2% of patients (95% confidence interval [ci], 46.5%−76.2%; figure 4a) — dlqi score ≤5: 93.3% of patients (95% ci, 81.7%−98.6%; figure 4b) — ≥5-point reduction in dlqi score: 78.9% of patients (95% ci, 62.7%−90.4%; figure 4c) figure 4. prespecified dlqi responses through week 64 a bproportion of patients with dlqi score of 0 or 1 (no negative effect on patients’ quality of life) bl 4 28 52 64 week 0 20 40 60 80 100 1.8% 18.2% 52.8% 56.3% 62.2% p er ce nt ± 95 % c i n = 55 45485355 proportion of patients with dlqi score ≤5 bl 4 28 52 64 week n = 55 45485355 13.0% 56.4% 94.3% 89.6% 93.3% 0 20 40 60 80 100 p er ce nt ± 95 % c i proportion of patients with ≥5-point reduction in dlqi score bl 4 28 52 64 week n = 45 42 384043 0% 44.4% 81.4% 82.5% 78.9% 0 20 40 60 80 100 p er ce nt ± 95 % c i c itt population. data are shown as percent ± 95% ci. bl, baseline; ci, confidence interval; dlqi, dermatology life quality index; itt, intention-to-treat. conclusions • treatment with tildrakizumab in patients with moderate-to-severe plaque psoriasis in a real-world setting significantly improved hrqol as measured by the pgwbi and dlqi references 1) reich k, et al. lancet. 2017;390(10091):276–88. 2) ilumya® (tildrakizumab-asmn) injection 100 mg/ml. full prescribing information. cranbury, nj; sun pharmaceutical industries, inc., 2022. 3) blauvelt a, et al. j eur acad dermatol venereol. 2019;33(12):2305–12. acknowledgments we thank the patients for their participation and dr. stephen j rozzo for contributions to the study. this study was funded by sun pharmaceutical industries limited. medical writing support was provided by elisabetta lauretti, phd, of alphabiocom, llc, and funded by sun pharma. disclosures jh is a speaker, advisor, and consultant for amgen, abbvie, celgene, eli lilly, janssen, and novartis; an advisor for galderma, mayne, and sanofi regeneron; an advisor and consultant for ortho dermatologic; and a speaker and advisor for sun pharma. jgv reports nothing to disclose. bs is an employee of sun pharmaceutical industries, inc. nb is an advisor, consultant, and investigator for abbvie, almirall, arcutis, biofrontera, bms, brickell, dermavant, epi health, ferndale, galderma, genentech, incyte, isdin, j&j, laroche-posay, leo, lilly, novartis, ortho, pfizer, p&g, regeneron, sanofi, stemline, sun pharma, and verrica. skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 629 brief article unilateral and localized bullous eruption in a 71-year-old woman karishma daftary, ba1, raj chovatiya, md, phd1 1department of dermatology, feinberg school of medicine at northwestern university, chicago, il a 71-year-old south asian woman presented with a 2-month, pruritic, bullous eruption localized only to the right leg, refractory to topical triamcinolone. her history was notable for a stage ivb small-cell neuroendocrine tumor in the mediastinum diagnosed two years prior. following initial carboplatin and etoposide, she was transitioned to combined ipilimumab / nivolumab for the past year. her tumor treatment course was notable for autoimmune hypothyroidism secondary to immunotherapy. she had otherwise stable disease without progression. skin examination revealed tense bullae filled with clear fluid, denuded vesicles, and postinflammatory hyperpigmentation at sites of healed bullae localized only to the right midlateral leg (figure 1). punch biopsy of an active bulla revealed a subepidermal acantholysis with spongiosis and numerous eosinophils, and direct immunofluorescence showed linear igg and c3 deposits at the dermal-epidermal junction (figure 2). these findings were consistent with unilateral, localized bullous pemphigoid (lbp). the eruption resolved completely without recurrence following twice-daily betamethasone dipropionate 0.05% ointment. bullous pemphigoid (bp) is the most commonly occurring autoimmune blistering dermatosis, affecting predominantly elderly patients in the 7th decade of life. it classically presents with diffuse pruritus and bullae. pathogenesis involves autoantibodies directed at hemidesmosomal proteins located at the dermal-epidermal junction – most commonly bp230 and bp180 (bp antigens 1 and 2, respectively). because these proteins are expressed throughout the skin, bp typically presents in a diffuse, symmetric pattern. in addition to thorough physical examination, diagnosis of bp is made with histology demonstrating subepidermal blisters with eosinophils, immunofluorescence depicting linear deposits of igg and c3 along the basement membrane, and quantification of autoantibodies using enzyme-linked immunoassay. lbp is a variant of bp in which lesions are restricted to certain sites. this variant is uncommon, with a recent cohort study suggesting a prevalence of 2.5% among bp patients.1 lbp often arises in areas of previous trauma or radiation and has been more frequently reported in the pretibial, vulvar, peristomal, and umbilical regions.2 case report discussion skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 630 figure 1. bullae localized to the right mid-lateral leg. figure 2. (a) lesional punch biopsy of active bulla demonstrating subepidermal acantholysis with spongiosis and numerous eosinophils (hematoxylin & eosin, 10x); peri-lesional punch biopsy showing igg (b) and c3 (c) deposits at the dermal-epidermal junction (direct immunofluorescence, 10x). the disease course is more benign than generalized bp due to its responsiveness to topical steroids, though lbp may also progress to generalized disease.3,4 triggering factors implicated in the development of lbp include radiation, burns, surgical procedures, phototherapy, venous stasis, and bacterial infections.1 several medications (e.g., angiotensin-convertingenzyme inhibitors, loop diuretics, gabapentin, iodine, dithranol, and tar) have also been reported to cause this variant.5 in our case, immunotherapy was the likely causative factor leading to the development of lbp. while widespread immunobullous eruptions like bp are well-described cutaneous adverse reactions associated with antictla-4 and -programmed cell death protein1 (pd-1) immunotherapy, reports of lbp following the use of these medications are extraordinarily rare.6 diagnosis of lbp is often delayed compared to generalized bp, as the differential diagnosis of a localized bullous eruption on the leg is broad and includes trauma (e.g., burn, friction, pressure), edema, arthropod assault, contact dermatitis, leukocytoclastic vasculitis, bullous diabeticorum, acute eczema, photodermatitis, and infection (namely herpesvirus and bacterial). for newonset bullous eruptions in patients receiving immunotherapy, it is important to consider clinical correlation alongside skin biopsy and skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 631 immunofluorescence to differentiate between etiologies. conflict of interest disclosures: rc has served as an advisory board member, consultant, and/or investigator for abbvie, arcutis, arena, argenx, beiersdorf, bristol myers squibb, dermavant, eli lilly and company, epi health, incyte, leo pharma, l’oréal, national eczema association, pfizer inc., regeneron, sanofi, and ucb, and speaker for abbvie, arcutis, dermavant, eli lilly and company, epi health, incyte, leo pharma, pfizer inc., regeneron, sanofi, and ucb. kd has no conflicts to disclose. funding: none corresponding author: raj chovatiya, md, phd department of dermatology northwestern university feinberg school of medicine 676 n st clair st, suite 1600 chicago, il 60611 email: raj.chovatiya@gmail.com references: 1. ständer s, kasperkiewicz m, thaçi d, et al. prevalence and presumptive triggers of localized bullous pemphigoid. j dermatol 2021;48(8):1257-1261. (in eng). doi: 10.1111/1346-8138.15912. 2. bernard p, antonicelli f. bullous pemphigoid: a review of its diagnosis, associations and treatment. am j clin dermatol 2017;18(4):513-528. (in eng). doi: 10.1007/s40257-017-0264-2. 3. salomon rj, briggaman ra, wernikoff sy, kayne al. localized bullous pemphigoid. a mimic of acute contact dermatitis. arch dermatol 1987;123(3):389-92. (in eng). doi: 10.1001/archderm.123.3.389. 4. wang y, mao x, liu y, li l. localized bullous pemphigoid: a case report. ann transl med 2020;8(5):249. (in eng). doi: 10.21037/atm.2020.01.104. 5. wenzel d, droms r, st john j, luffman c, levin na. localized bullous pemphigoid after knee replacement surgery. dermatol online j 2021;27(3) (in eng). 6. amber kt, valdebran m, lu y, de feraudy s, linden kg. localized pretibial bullous pemphigoid arising in a patient on pembrolizumab for metastatic melanoma. j dtsch dermatol ges 2018;16(2):196-198. (in eng). doi: 10.1111/ddg.13411. skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 668 original research sunscreen knowledge and sun protective behaviors among medical students at a southern us institution meagan mandabach olivet, ba1, lauren c.s. kole, md2 1 the university of alabama at birmingham heersink school of medicine, birmingham, al 2 the university of alabama at birmingham department of dermatology, birmingham, al skin cancer is the most common malignancy in the united states. though it is largely preventable, few adults regularly use sunscreen on their face1. sun protection is crucial because research indicates that sunburn, regardless of age, increases the risk of skin cancer2. practices such as seeking shade and wearing protective clothing are also vital to reduce ultraviolet (uv) radiation3. previous literature highlights that sun protection and sunscreen use is different among demographic groups. for example, females are more likely to apply sunscreen than their male counterparts4 and certain ethnic groups, including black individuals, are less likely to apply sunscreen than white individuals5. additionally, among those that wear sunscreen, correct application is not consistent. for example, in a study by holman et al., 40% of participants that wore sunscreen were uncertain if they applied broad spectrum5. compared to the general adult population, medical students are uniquely positioned in their level of knowledge to carry out best health practices in a multitude of areas. abstract introduction: literature has demonstrated that medical students have discrepancies in their knowledge and their execution of best practices concerning sun protection. additionally, despite knowing the harms of tanning, medical students acknowledge they desire tan skin. methods: a survey was sent to medical students at a southeastern institution to determine their knowledge of sun safety and their personal practices. the survey was distributed through institutional emails and student messaging applications. current medical students at the home institution were eligible to complete the survey. the survey was designed with guidelines from the american academy of dermatology in mind. chi square analysis was performed by spss version 28.0.1.1 (14). results: the majority of medical student are knowledgeable of best sun protective practices, though many students do not carry out these practices. for example, 88% of students know to reapply sunscreen every 2 hours; however, only 29% of students always reapply at the correct interval. conclusion: medical students are knowledgeable of best practices for preventing sun damage; however, their personal behaviors can deviate and societal pressure for some students to have “tanned” skin is challenging to overcome. introduction skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 669 though previous research demonstrates that medical students are knowledgeable of best sun protective practices, medical students have discrepancies in their knowledge and their execution of those practices6,7. although students in a study by novitasari et al. knew that applying sunscreen every 2 hours while outdoors was recommended, less than 50% of students adhered to this recommendation in their daily practice6. additionally, despite knowing the harms of tanning, medical students still acknowledge they desire tan skin7.the purpose of this study was to ascertain the knowledge of sun protection and the implementation of these practices by medical students at a united states southeastern institution. an online survey was developed to ascertain students’ knowledge and sun protective behaviors. the survey was created on qualtrics with questions sourced from previous literature, the american academy of dermatology, and investigator collaboration. all current medical students at the university of alabama at birmingham heersink school of medicine during the academic year of 2021 – 2022 were included. students were recruited through institutional listserv emails, class messaging boards, and posters on campus. responses were coded before analysis. participants’ self-reported race was broken down into white and non-white students. questions regarding objective knowledge were classified as correct or incorrect. in terms of behavior questions, responses were classified as “more often” if a student selected “always” or “sometimes.” all other responses were coded as “less often.” chi-square analysis was performed on spss version 28.0.1.1 (14). with 268 out of 744 students responding, the survey had a response rate of 36%. the majority of responding medical students were white (75%), female (63%), and belonged to the first-year class (36%). the median age was 24. full demographic information is outlined in table 1. medical students are well-versed in best practices for sun protection (table 2). for example, 98% of students endorse that sunscreen can protect against skin cancer. only two questions out of seven had less than 80% of students responding correctly. 70% of students endorse that a “base tan” does not protect against further sun damage. in addition, 59% of students state that sunscreen should be applied 15 minutes before going outdoors. demographic differences were identified through chi-square analysis (table 3a-c). female students are more likely to correctly identify the photo aging benefits of sunscreen (p=0.022) and that a “base tan” does not protect from further sun damage (p=0.006). white students were more likely to correctly identify >30 as the recommended spf level (p<0.001) and that a base tan does not protect skin from further sun damage (p=0.010). dermatology patients are more likely to correctly state the recommended level of spf (p=0.017). results demonstrate that students are less likely to apply their knowledge (table 4). for example, only 48% of students more often wear sunscreen when spending time outdoors. just 10% of students will wear long sleeves to protect themselves. some demographic differences were found through chi-square analysis (table 5a-c). female students were more likely to wear sunscreen outdoors (p=0.003) and indoors (p<0.001) and wear long sleeves when in the sun (p=0.04). white students were more likely to reapply sunscreen every 2 hours (p<0.001) and wear sunscreen indoors (p=0.016). nonwhite students were more likely to wear long methods results skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 670 table 1. demographics of survey respondents. percentage frequency medical student year ms1 36 91 ms2 35 88 ms3 15 37 ms4 14 34 gender identity male 37 92 female 63 157 non-binary 1 2 prefer not to say 0 0 race white 75 188 black 6 14 american indian or alaskan native 1 3 asian 15 38 native hawaiian or pacific islander 0 0 other 3 7 ethnicity hispanic or latino 10 23 non-hispanic or latino 90 127 age mean 25 median 24 minimum 22 skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 671 table 2, 3a-c. medical students are well-versed in best practices for sun protection. female students are more likely to correctly identify the photoaging benefits of sunscreen (p=0.022) and that a “base tan” does not protect from further sun damage (p=0.006). white students were more likely to correctly identify >30 as the recommended spf level (p<0.001) and that a base tan does not protect skin from further sun damage (p=0.010). dermatology patients are more likely to correctly state the recommended level of spf (p=0.017). table 2. student’s knowledge of sun protection correct response % correct sunscreen should be reapplied every 2 hours when outdoors 87 sunscreen be applied 15 minutes before going outdoors 59 the recommended level of spf in sunscreen products is >spf 30 81 sunscreen can protect against skin cancers 98 sunscreen can protect against photo-aging 92 a “base tan” does not protect skin from further sun damage 70 people with dark (brown/black) skin need to wear sunscreen 97 skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 672 table 3a. students’ knowledge of sun protection: males v females correct response % m % f pearson x2 df asymptotic significance sunscreen can protect against photo-aging 85 95 7.631 2 0.022 a “base tan” does not protect skin from further sun damage 55 78 14.440 4 0.006 table 3b. students’ knowledge of sun protection: white vs non-white correct response % w % nw pearson x2 df asymptotic significance the recommended level of spf in sunscreen products is >spf 30 86 64 14.931 1 0.000 a “base tan” does not protect skin from further sun damage 74 54 9.188 2 0.010 table 3c. students’ knowledge of sun protection: dermatology patient vs nondermatology patient correct response % w % nw pearson x2 df asymptotic significance the recommended level of spf in sunscreen products is >spf 30 85 75 8.208 2 0.017 skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 673 table 4, 5a-c. results demonstrate that students are less likely to apply their knowledge. female students are more likely to wear sunscreen outdoors (p=0.003) and indoors (p<0.001) and wear long sleeves when in the sun (p=0.04). white students are more likely to reapply sunscreen every 2 hours (p<0.001) and wear sunscreen indoors (p=0.016). non-white students are more likely to wear long sleeves when in the sun (p=0.045). dermatology patients are more likely to report wearing sunscreen outdoors (p=0.036) table 4. students’ sun protective behaviors students “always” or “most of the time” … % wear sunscreen when outdoors 48 wear sunscreen when indoors 22 reapply sunscreen every 2 hours during outdoor activities 29 wear long sleeves when spending time in the sun 10 seek shade 43 skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 674 table 5a. students’ sun protective behaviors: male vs female “i more often…” % m % f pearson x2 df asymptotic significance wear sunscreen when outdoors 33 55 11.333 2 0.003 wear sunscreen when indoors 9 27 17.362 2 <0.001 wear long sleeves when spending time in the sun 5 12 6.229 2 0.044 table 5b. students’ sun protective behaviors: white vs non-white response % w % nw pearson x2 df asymptotic significance wear sunscreen when outdoors 86 64 14.931a 1 0.000 wear sunscreen when indoors 74 54 9.188a 2 0.010 reapply sunscreen every 2 hours during outdoor activities 35 11 11.443 1 0.001 wear long sleeves when spending time in the sun 8 17 4.018 1 0.045 table 5c. students’ knowledge of sun protection: dermatology patient vs nondermatology patient response % d % nd pearson x2 df asymptotic significance wear sunscreen when outdoors 56 37 6.657 2 0.036 skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 675 table 6, 6a. white students were more likely to feel more attractive with tan skin (p<0.001), tan their skin in the sun during the summer (p=0.004), and tan their skin in sun before a vacation (p=0.013). table 6. students’ tanning practices responses % more true i feel more attractive with tanned skin 50 i think others look more attractive with tanned skin 41 i believe skin looks healthier when it is tanned 27 in the winter, i purposely tan my skin in the sun 2 in the summer, i purposely tan my skin in the sun 17 table 6a. students’ tanning practices: white vs non-white response % w % nw pearson x2 df asymptotic significance i feel more attractive with tanned skin 76 67 14.500 1 0.000 purposely tan skin in the sun before i go on vacation 10 0 6.107 1 0.013 skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 676 sleeves when in the sun (p=0.045). dermatology patients were more likely to report wearing sunscreen outdoors (p=0.036). in terms of tanning practices (table 6), 50% of students responding feel more attractive with tan skin. white students were more likely to feel more attractive with tan skin (p<0.001), tan their skin in the sun during the summer (p=0.004), and tan their skin in sun before a vacation (p=0.013) (table 6a). the majority of medical students surveyed at this southeastern institution were knowledgeable of best sun protective practices and the risks of sun exposure. although knowledge among the general student population was strong, there were some significant differences in their understanding of guidelines among demographic groups. female students being more likely to identify that sunscreen protects against photo-aging and that a base tan does not protect from further sun damage correlates with previous research that highlights differences between males and females in sun-protective behaviors. for example, a study by abroms, revealed that female participants, when asked about their reasoning for sunscreen use, acknowledged the role of sunscreen in preventing photoaging4. in their study, this desire to utilize sunscreen for cosmetic factors was not present among the male participants4. our study also demonstrated differences in knowledge when controlling for race. literature that discusses differences in race and skin cancer knowledge should be viewed with nuance. in some studies, black and hispanic participants demonstrate less knowledge of sun protection than their white counterparts8. still, more recent data demonstrates that further differences among black and hispanic knowledge can be better attributed to their region of residency than their ethnicity9. our data correlates with a difference in knowledge between white and non-white students; however, further studies would need to be conducted to understand why this difference was found in the studied medical student population. though the students’ understanding of sun protection was strong, the application of the practices was varied. for example, 87% of students endorse that sunscreen should be reapplied every two hours; however, only 29% of students “more often” reapply at this interval. only 48% of students apply sunscreen when they spend time outdoors. despite having the cognitive tools to protect themselves from uv damage, medical students at this institution are not consistent in sunscreen application and avoiding risky behavior. there were some demographic differences in student sunscreen application. for example, data that female-identifying students were more likely to wear sunscreen overall is consistent with studies conducted in the general population. holman et al. found that women were more likely than men to wear sunscreen on their face1. they found that women were more likely than men to adopt sun protective practices including wearing sunscreen, wearing protective clothing, and seeking shade10. a study by chen et al. demonstrates this trend persists even among melanoma survivors10. in terms of race and sun protective behaviors, no difference was found between white and non-white students in applying sunscreen outdoors. when accounting for reapplication and wearing sunscreen indoors, white students were more likely to adhere to these practices. when comparing these findings to other studies, there has been literature documenting that black discussion skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 677 patients are more likely to perceive themselves at low risk of skin cancer and have lower engagement with sun protective practices1,9. in a study by lunsford et al., black and hispanic individuals were more likely to report never or rarely using sun protection9. though non-white medical students may have more understanding of the risks of uv radiation, cultural practices may take precedence. when considering tanning practices, 50% of students endorse that it is more often true of them to feel more attractive with a tan. in our study, there was no statistical difference between men and women in terms of likelihood to tan or their personal feelings of being attractive with a tan. this result deviates from research in the general population. though women are more likely to engage in sun protection than men, studies reveal that women are more likely to use report a desire to be tan, sunbathe, and use tanning beds11,12,13. differences emerged when accounting for the race of responding students. white students were more likely to report “feeling more attractive” with tan skin and more likely to tan their skin during the summer and before a vacation. these findings are consistent with behaviors identified in other studies14. reasons for tanning are a subject of curiosity given the wide public knowledge of its dangers. in a study by neenan et al. among community college students, the most often cited reason for using tanning beds was “i think i look better when i am tan”11. a similar study conducted at the ohio university heritage college of osteopathic medicine in athens had similar findings among the medical student population. most participants were aware of how to use sunscreen properly and how to avoid excess sun; however, many students participating in tanning and perceived tan skin as healthier7. this demonstrates further that while medical students may be uniquely poised in their understanding of healthy practices, they are still subject to cultural norms. our study deviated from these findings, given less than half of respondents endorsed that their skin appeared healthier when tan. the desire to be tan is well documented in western culture. though using sunscreen has been emphasized as an important tool for anti-aging to maintain the cultural beauty standard of youth, media can display conflicting messages15. mcwhirter and hoffman-goetz conducted an analysis of skin cancer and uv behaviors in u.s. magazines15. they found that women’s magazines were more likely to endorse sun protective behaviors and promote the use of sunscreen than men’s magazines15. though explicit messaging was different between groups, the implicit messaging of tan skin being desirable was present in both15. both men’s and women’s magazines contained images of models sporting the tanned look15. these tanned images impact cultural norms and continue to emphasize that those with tan skin are attractive16. medical students even with their knowledge of skin cancer and preventing disease are not immune to the cultural pressure to adhere to a particular standard of beauty. in research in the general public, a study by williams et al. demonstrates that giving individuals information about photo-aging and showing participants uv photos of themselves is effective motivation for future indoor tanning but no significant impact on future uv exposure intentions17. mahler et al. similarly assessed the effects of appearance based tactics on sun protection. in their follow-up, they determined that participants had reduced incidental sun exposure during the subsequent year18. additionally, they reported had increased sun protection skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 678 behaviors and spectrophotometric evidence decreased skin darkening at the postsummer follow-up and one-year later18. studies conducted in the medical student population have yielded similar results. students at the university of western ontario retained sunscreen knowledge at the oneyear follow-up and reported fewer sunburns; however, they continued to perceive a tan appearance as healthy19. our study also highlighted the role that dermatologists play in contributing to patients’ knowledge of sun protection and influencing their daily behaviors. of graduating seniors at this southeastern institution, 36% matched into a primary care specialty in 2022, while only 2% matched into dermatology20. while dermatologists are particularly positioned to counsel, intervene, and manage skin disorders, primary care providers also play an important role in screening for skin cancer and helping their patients form healthy habits. research has shown that physicians who carry out healthy practices themselves have improved behavioral counseling for their patients21. additionally, research has shown that many patients are never counseled on the importance of wearing sunscreen22. they were more likely to receive counseling from a dermatologist (35%), and only 5.2% report that they were counseled by their primary care provider22. the importance of medical students understanding and adhering to best sun protective practices is paramount not only for their personal health, but for overall public health. limitations of this study include the sample size and population. the majority of the responding students were white and other self-reported race groups were too small for meaningful analysis. repeating this study at other institutions with a more diverse student population would allow for more meaningful breakdown among individual groups. the majority of medical students are aware of safe sun practices and know the benefits, such as preventing skin cancer and photoaging, that can result. though there is broad awareness across demographic groups, students still endorse the desire to be tan and do not fully adhere to sun protective guidelines. these results demonstrate that medical students are not immune to the cultural pressure to adhere to the dominant standard of beauty. physicians who carry out healthy practices themselves have improved behavioral counseling for their patients20,21. given that more medical students will match into primary care specialties than dermatology, fostering healthy behaviors in all students is imperative. medical students that regularly protect themselves from uv radiation may be more likely to counsel their patients to do the same. continuing to improve education for medical students not only improves personal health, but also benefits their future patients. conflict of interest disclosures: none funding: none corresponding author: meagan mandabach olivet, ba the university of alabama at birmingham department of dermatology 1670 university blvd birmingham, al 35233 email: mkmandab@uab.edu references: 1. holman dm, berkowitz z, guy gp jr, hawkins na, saraiya m, watson m. patterns of sunscreen use on the face and other exposed skin among us adults. j am acad dermatol. 2015 jul;73(1):83-92.e1. doi: conclusion skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 679 10.1016/j.jaad.2015.02.1112. epub 2015 may 19. pmid: 26002066; pmcid: pmc4475428. h 2. dennis lk, vanbeek mj, beane freeman le, smith bj, dawson dv, coughlin ja. sunburns and risk of cutaneous melanoma: does age matter? a comprehensive meta-analysis. ann epidemiol. 2008;18(8):614-627. 3. us department of health and human services. the surgeon general’s call to action to prevent skin cancer. washington, dc: us dept of health and human services, office of the surgeon general; 2014. 4. abroms l, jorgensen cm, southwell bg, geller ac, emmons km. gender differences in young adults' beliefs about sunscreen use. health educ behav. 2003 feb;30(1):29-43. doi: 10.1177/1090198102239257. pmid: 12564666. 5. holman dm, ding h, guy gp, watson m, hartman am, perna fm. prevalence of sun protection use and sunburn and association of demographic and behaviorial characteristics with sunburn among us adults. jama dermatol. 2018;154(5):561–568. doi:10.1001/jamadermatol.2018.0028 6. novitasari, triana & prajitno, subur & indramaya, diah. (2020). behavior of sunscreen usage among medical students. berkala ilmu kesehatan kulit dan kelamin. 32. 174. 10.20473/bikk.v32.3.2020.174-181. 7. ivanov nn, swan a, guseman eh, whipps j, jensen ll, beverly ea. medical students' knowledge, attitudes, and behaviors with regard to skin cancer and sun-protective behaviors. j am osteopath assoc. jul 1 2018;118(7):444-454. doi:10.7556/jaoa.2018.098 8. cheng c.e., irwin b., mauriello d. health disparities among different ethnic and racial middle and high school students in sun exposure beliefs and knowledge. j. adolesc. health. 2010;47(1):106–109. 9. lunsford nb, berktold j, holman dm, stein k, prempeh a, yerkes a. skin cancer knowledge, awareness, beliefs and preventive behaviors among black and hispanic men and women. preventive medicine reports. 2018 dec (12): 203-209. doi: 10.1016/j.pmedr.2018.09.017. 10. chen j, shih j, tran a, mullane a, thomas c, aydin n, misra s. gender-based differences and barriers in skin protection behaviors in melanoma survivors. j skin cancer. 2016;2016:3874572. doi: 10.1155/2016/3874572. epub 2016 aug 25. pmid: 27648306; pmcid: pmc5014947. 11. neenan a, suzanne lea c, lesesky eb. reasons for tanning bed use: a survey of community college students in north carolina. north carolina medical journal. 2012;73(2):89. doi:10.18043/ncm.73.2.89 12. meghan m. gillen & charlotte n. markey (2012) the role of body image and depression in tanning behaviors and attitudes, behavioral medicine, 38:3, 7482, doi: 10.1080/08964289.2012.685499 13. ashley k. day, carlene j. wilson, amanda d. hutchinson & rachel m. roberts (2017) australian young adults’ tanning behaviour: the role of ideal skin tone and sociocultural norms, australian journal of psychology, 69:2, 8694, doi: 10.1111/ajpy.12121 14. heckman cj, coups ej, manne sl. prevalence and correlates of indoor tanning among us adults. j am acad dermatol. 2008 may;58(5):769-80. doi: 10.1016/j.jaad.2008.01.020. epub 2008 mar 6. pmid: 18328594; pmcid: pmc2601681. 15. mcwhirter, j.e., hoffman-goetz, l. coverage of skin cancer risk factors and uv behaviors in popular u.s. magazines from 2000 to 2012. j canc educ 31, 382–388 (2016). https://doiorg.ezproxy3.lhl.uab.edu/10.1007/s13187-0150808-1 16. jennifer e. mcwhirter, laurie hoffman-goetz, systematic review of population-based studies on the impact of images on uv attitudes and behaviours, health promotion international, volume 30, issue 2, june 2015, pages 397– 410, https://doi.org/10.1093/heapro/dat031 17. williams al, grogan s, clark-carter d, buckley e. appearance-based interventions to reduce ultraviolet exposure and/or increase sun protection intentions and behaviours: a systematic review and meta-analyses. br j health psychol. 2013 feb;18(1):182-217. doi: 10.1111/j.2044-8287.2012.02089.x. epub 2012 sep 18. pmid: 22989352. 18. mahler h, kulik j, gerrard m, gibbons f. longterm effects of appearance-based interventions on sun protection behaviors. health psychology : official journal of the division of health psychology, american psychological association. 06/01 2007;26:350-60. doi:10.1037/02786133.26.3.350 19. liu, barankin, b., howard, j., & guenther, l. c. (2001). one-year followup on the impact of a sun awareness curriculum on medical students’ knowledge, attitudes, and behavior. journal of cutaneous medicine and surgery, 5(3), 193–200. https://doi.org/10.1177/120347540100500301 20. the university of alabama at birmingham heersink school of medicine. 2022 match results by residency type. march 2022. https://doi.org/10.1080/08964289.2012.685499 https://doi.org/10.1111/ajpy.12121 https://doi-org.ezproxy3.lhl.uab.edu/10.1007/s13187-015-0808-1 https://doi-org.ezproxy3.lhl.uab.edu/10.1007/s13187-015-0808-1 https://doi-org.ezproxy3.lhl.uab.edu/10.1007/s13187-015-0808-1 https://doi.org/10.1093/heapro/dat031 https://doi.org/10.1177/120347540100500301 skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 680 accessed november 15, 2022. https://www.uab.edu/medicine/home/images/edu cation/2022-match-results-by-specialty.pdf 21. carlos s, rico-campà a, fuente-arrillaga c, echavarri m, fernandez-montero a, gea a, salazar c, martínez-gonzález ma. do healthy doctors deliver better messages of health promotion to their patients?: data from the sun cohort study. european journal of public health. 2020 june; 30) volume 30 (3): 438-444. https://doi.org/10.1093/eurpub/ckaa019 22. vasicek be, szpunar sm, manz-dulac la. patient knowledge of sunscreen guidelines and frequency of physician counseling: a crosssectional study. j clin aesthet dermatol. 2018 jan;11(1):35-40. epub 2018 jan 1. pmid: 29410729; pmcid: pmc5788267. https://www.uab.edu/medicine/home/images/education/2022-match-results-by-specialty.pdf https://www.uab.edu/medicine/home/images/education/2022-match-results-by-specialty.pdf https://doi.org/10.1093/eurpub/ckaa019 ♦ ixekizumab is a high-affinity monoclonal antibody that selectively targets interleukin-17a1 • demonstrated significant efficacy in the treatment of moderate-to-severe psoriasis2-5 • maintained improvements in skin clearance for up to 4 years in an open-label extension of a phase 2 trial6 efficacy, health-related outcomes, and safety of ixekizumab for up to five years of open-label treatment in a phase 2 study in chronic plaque psoriasis andrew blauvelt,1 kenneth gordon,2 craig leonardi,3 claus zachariae,4 russel burge,5 terri ridenour,5 missy mckean-matthews,5 sandra garces,5 gregory cameron5 1oregon medical research center, portland, usa; 2medical college of wisconsin, milwaukee, usa; 3st. louis university school of medicine, st. louis, usa; 4university hospital of copenhagen gentofte, copenhagen, denmark; 5eli lilly and company, indianapolis, usa methods background 2017 fall clinical dermatology conference (fall cdc 2017); las vegas, nevada; october 12-15, 2017; previously presented at eadv 2017 sponsored by eli lilly and company and/or one of its subsidiaries disclosures ♦ a. blauvelt has served as a scientific adviser and/or clinical study investigator for: abbvie, aclaris, allergan, almirall, amgen, boehringer ingelheim, celgene, dermavant, dermira, eli lilly and company, genentech/roche, glaxosmithkline, janssen, leo pharma, merck sharp & dohme, novartis, pfizer, purdue pharma, regeneron, sandoz, sanofi genzyme, sienna pharmaceuticals, sun pharma, ucb, valeant, and vidac, and as a paid speaker for eli lilly and company, janssen, regeneron, and sanofi genzyme; k. gordon has served as a consultant for: abbvie, amgen, boehringer ingelheim, celgene, dermira, eli lilly and company, janssen, novartis, and pfizer, and has received grants from: abbvie, amgen, celgene, eli lilly and company and janssen; c. leonardi is on the speaker’s bureau of: abbvie, celgene, and leo pharma, is a consultant for: abbvie, amgen, dermira, eli lilly and company, janssen, leo pharma, pfizer, sandoz, and ucb pharma, has a conflict with: actavis, abbvie, amgen, celgene, coherus, cermira, eli lilly and company, galderma, janssen, leo pharma, merck, novartis, pfizer, sandoz, stiefel, and wyeth; c. zachariae has received honoraria from: eli lilly and company, novartis, and pfizer, and has consulted for and participated in advisory boards for: abbvie, amgen, eli lilly and company, janssen-cilag, novartis, and takeda and has been a clinical study investigator for: abbvie, amgen, eli lilly and company, leo pharma, msd, novartis, regeneron, and takeda; r. burge, t. ridenour, m. mckean-matthews, s. garces, and g. cameron are shareholders and employees of eli lilly and company ♦ this study was sponsored by eli lilly and company. medical writing services were provided by samantha forster, phd, of proscribe – part of the envision pharma group, and were funded by eli lilly and company references 1. liu l, et al. j inflamm res. 2016;9:39-50. 2. leonardi c, et al. n eng j med. 2012;366:1190-1199. 3. gordon kb, et al. j am acad dermatol. 2014;71:1176-1182. 4. griffiths ce, et al. lancet. 2015;386:541-551. 5. gordon kb, et al. n eng j med. 2016;375:345-356. 6. gordon kb, et al. j eur acad dermatol venereol. 2016;30(suppl.6):17. 7. paul c, et al. br j dermatol. 2015;173:1378-1399. results statistical analyses ♦ descriptive statistics (n, mean change, 95% confidence intervals) are provided ♦ any imputation was performed using the last observation carried forward method table 1. baseline demographics and disease characteristics at the start of part b (open-label extension) values are mean (standard deviation) unless otherwise stated dlqi=dermatology life quality index; napsi=nail psoriasis severity index; pasi=psoriasis area and severity index; patga=patient’s global assessment of disease activity; pssi=psoriasis scalp severity index; vas=visual analog scale ♦ throughout the open-label extension, most treatment-emergent adverse events were considered mild or moderate overall ♦ among the 24 patients experiencing ≥1 treatment-emergent serious adverse event, the most frequent (>4%) were: infections and infestations (n=6, 5.0%), cardiac disorders (n=5, 4.2%) and benign, malignant and unspecified neoplasms (n=5, 4.2%) table 4. adverse events leading to discontinuation during open-label treatment a the ixe dose was reduced to 80 mg following a protocol amendment to align with the dose regimen used in phase 3 trials b includes ongoing patients c patient consent was required to continue beyond week 240 ixe=ixekizumab; ole=open-label extension; pasi 75=psoriasis area and severity index 75% response; sc=subcutaneous; spga=static physician’s global assessment conclusions ♦ ixekizumab provided sustained complete to near complete skin clearance up to 5 years • pasi 75 at week 260: 83% (locf)/98% (observed) • pasi 90 at week 260: 68% (locf)/86% (observed) • pasi 100 at week 260: 45% (locf)/58% (observed) • spga (0,1) at week 240: 64% (locf)/78% (observed) • spga (0) at week 240: 48% (locf)/59% (observed) ♦ ixekizumab provided sustained improvements in dlqi and itch reduction through 4.5 years of treatment • dlqi mean change from baseline at week 240: -8.3 (locf) • itch vas mean change from baseline at week 240: -43.6 (locf) ♦ the most common adverse events occurring during the open-label treatment period were consistent with those previously reported in clinical results for patients treated with ixekizumab for a shorter time period1-4 objective ♦ to assess the efficacy, health-related outcomes, and safety of ixekizumab after 5 years of treatment in the open-label extension of a phase 2 trial (nct01107457) figure 3. pasi response rates with ixekizumab were maintained over 5 years of open-label treatment figure 1. study design ♦ study included patients with chronic plaque psoriasis for ≥6 months, ≥10% body surface area involvement, static physician’s global assessment ≥3, and psoriasis area and severity index ≥12 characteristic n=120 age, years 47.2 (12.3) male, n (%) 70 (58.3) body weight, kg 95.4 (26.4) pasi 17.9 (5.9) nail psoriasis, n (%) 52 (43.3) napsi 40.5 (41.7) scalp psoriasis, n (%) 91 (75.8) pssi 19.3 (13.3) dlqi 10.9 (6.1) itch vas 58.3 (26.0) patga (0,1) n (%) 1 (0.8) incidence, n (%) (n=120) discontinued due to an adverse event 13 (10.8) exposure during pregnancy 2 (1.7) alanine aminotransferase increased 1 (0.8) hepatic enzyme increased 1 (0.8) hidradenitis 1 (0.8) invasive ductal breast carcinoma 1 (0.8) non-small cell lung cancer metastatic 1 (0.8) osteomyelitis 1 (0.8) psoriatic arthropathy 1 (0.8) pyelonephritis 1 (0.8) rectal adenocarcinoma 1 (0.8) rectal adenoma 1 (0.8) urinary tract obstruction 1 (0.8) figure 2. assessments dlqi=dermatology life quality index; hrqol=health-related quality of life; pasi=psoriasis area and severity index; spga=static physician’s global assessment; vas=visual analog scale static physician’s global assessment spga every 4 weeks to week 240 score range: 0 to 5 proportion of patients achieving spga (0,1) proportion of patients achieving remission of psoriasis plaques by spga (0) 4 4 psoriasis area and severity index pasi every 4 weeks changes from baseline in pasi • proportion of patients with at least 75% reduction of pasi (pasi 75) • at least 90% reduction (pasi 90) • 100% reduction (pasi 100) (where pasi 100 refers to complete resolution of plaques) safety evaluated up to 260 weeks (5 years) of treatment 260 hrqol dlqi every 24 weeks to week 240 score range: 0 to 30 (less to greater impairment) score of 0 or 1 = no effect of psoriasis on hrqol itch itch vas every 24 weeks to week 240 score range: 0 (none) to 100 (severe) 24 24 figure 4. spga response rates with ixekizumab were maintained over 4.5 years of open-label treatment data points shown at weeks 0, 4, 12, 24, 52, 104, 156, 208, 240 a spga was only collected to week 240, per protocol locf=last observation carried forward; spga=static physician’s global assessment figure 5. ixekizumab provides sustained improvements in dlqi and itch reduction in moderate-to-severe psoriasis through 4.5 years of treatment, locf data points shown at weeks 0, 24, 48, 96, 144, 192, 240 a defined as the last available value before the first dose in the randomized, placebo-controlled treatment period b dlqi and itch vas were only collected to week 240, per protocol c mcid for dlqi is improvement from baseline ≥57 ci=confidence interval; dlqi=dermatology life quality index; locf=last observation carried forward; mcid=minimal clinically important difference; vas=visual analog scale table 2. incidence of treatment-emergent adverse events over time table 3. most common (≥10%) adverse events during open-label treatment system organ class preferred term incidence, n (%) (n=120) infections and infestations 83 (69.2) nasopharyngitis 29 (24.2) sinusitis 17 (14.2) upper respiratory tract infection 15 (12.5) urinary tract infection 13 (10.8) nervous system disorders 22 (18.3) headache 12 (10.0) adverse events, n (%) ≥1 to ≤52 weeks (n=120, py=108) >52 to ≤104 weeks (n=102, py=95) >104 to ≤156 weeks (n=90, py=86) >156 to ≤208 weeks (n=83, py=80) >208 to ≤260 weeks (n=76, py=72) ≥1 day (n=120, py=455) teaes 72 (60.0) 68 (66.7) 65 (72.2) 54 (65.1) 38 (50.0) 105 (87.5) saes 7 (5.8) 4 (3.9) 6 (6.7) 4 (4.8) 8 (10.5) 24 (20.0) py=person years; sae=serious adverse event; teae=treatment-emergent adverse event data points shown at weeks 0, 4, 12, 24, 52, 104, 156, 208, 240, 260 locf=last observation carried forward; pasi 75/90/100=psoriasis area and severity index 75%/90%/100% response randomized, placebo-controlled, treatment treatment-free period open-label extension 6 sc doses at weeks 0, 2, 4, 8, 12, 16 week 0 to 88: 120 mg sc ixe every 4 weeks week 92 to 124 onwards: 80 mg sc ixe every 4 weeksa eligible to enroll in ole when response < pasi 75 or at week 32 patients enrolled n=120 discontinued treatment during ole, n=120 adverse events, n=13 sponsor decision, n=66 patient decision, n=26 lost to follow up, n=10 other, n=5 all patients n=142 completed n=129 completed part b (240 weeks) n=74b week 0 week 20 20-32 wks week 0 of ole long-term open-label treatment week 240 week 260 entered part c (week 244-260) n=73c part a part b part c dlqi=dermatology life quality index; locf=last observation carried forward; pasi 75/90/100=psoriasis area and severity index 75%/90%/100% response; spga=static physician’s global assessment; vas=visual analog scale 0 15652 104 208 240 260 0 60 100 80 40 20r es po ns e (% ) weeks of open-label treatment pasi 75 pasi 90 pasi locf (n=120) pasi 100 0 15652 104 208 240 260 0 60 100 80 40 20r es po ns e (% ) weeks of open-label treatment pasi 75 pasi 90 pasi observed pasi 100 n patients 120 758292102 74 65 0 60 100 80 40 20r es po ns e (% ) weeks of open-label treatment spga (0,1) spga (0) spga locf (n=120) 0 15652 104 208 240a 0 15652 104 208 240a 0 60 100 80 40 20r es po ns e (% ) weeks of open-label treatment spga observed n patients120 758292102 74 spga (0,1) spga (0) 0 15652 104 208 240b -60 -20 0 -40 m ea n c ha ng e fr om b as el in e, a 95 % c i weeks of open-label treatment itch vas (n=120) -43.6 0 15652 104 208 240b -15 -5 0 -10 m ea n c ha ng e fr om b as el in e, a 95 % c i weeks of open-label treatment dlqi (n=120) mcidc -8.3 fc17posterlillyblauveltefficacyixekizumab.pdf skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 492 in-depth review a review of the risk of cutaneous squamous cell carcinoma after vismodegib therapy jenne p. ingrassia, ba1, jacqueline maher, md1, abigail cline, md1,2 1 new york medical college, school of medicine, valhalla, ny 2 new york city health and hospitals, department of dermatology, new york, ny vismodegib is a hedgehog inhibitor (hhi) approved by the food and drug administration (fda) to treat locally advanced and metastatic basal cell carcinomas (bccs) not treatable with surgical resection and/or radiation. while some studies found that vismodegib may increase the risk for cutaneous squamous cell carcinoma (cscc), larger studies have reported published conflicting findings.1,2,4 this study reviews the current literature to assess the risk of vismodegib with the development of cscc. abstract introduction: since vismodegib’s approval for advanced or metastatic basal cell carcinoma, there has been concern over vismodegib’s potential to induce secondary neoplasms of the skin, such as cutaneous squamous cell carcinoma (cscc). objective: in this article, we provide a comprehensive review of the literature on vismodegib’s relationship to cscc. methods: a systematic search of pubmed and ovid medline was performed with terms “vismodegib” and “squamous cell carcinoma.” studies ranged from may 2013 to january 2022. results: 25 articles were ultimately included in the review. in total, of the 2576 patients included in the review, there were 197 csccs reported. the median duration of treatment with vismodegib was 3 months. discussion: numerous reports have published conflicting findings. while one retrospective cohort study did find an increased risk, additional studies have found that the rates of cscc are comparable between those exposed and those not exposed to vismodegib. limitations of this review are only using two databases to search for articles, the limited number of published articles on the topic, and the quality of the articles included. conclusions: because a causal relationship between vismodegib and cscc has not been proven, its use should not be avoided due to concerns of causing cscc. however, patients treated with vismodegib should be closely monitored by dermatologists to evaluate for any suspicious changes. large-scale, prospective, multi-center studies should be performed to definitively determine the risk of cscc and vismodegib. it has been proposed that vismodegib may select for tumor cells utilizing the ras/mapk pathways. introduction skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 493 a literature search of pubmed and ovid medline was conducted with terms “vismodegib” and “squamous cell carcinoma.” between may 2013 and january 2022, 245 articles were identified, and 2 additional articles were found through handsearch of the literature (figure 1). removing duplicates resulted in 168 articles, of which 130 articles were excluded based on lack of relevance to the research question. 38 total articles were assessed for eligibility, and 14 were ultimately excluded based on lack of applicability. 25 articles were ultimately included in the review. of the 25 articles included in the review, 14 reported patient outcome data and statistics on cscc development after vismodegib exposure, whereas the remaining 11 were review articles or commentaries on the topic. in this review, a total of 2576 patients were treated with vismodegib and 197 cases of cscc were reported. the duration of vismodegib treatment until cscc development ranged from 2 weeks to 2.7 years across all studies included. the median duration of treatment was 3 months (table 1). the initial phase ii trial of vismodegib enrolled 96 patients but included safety data of patients from other trials for a total of 400 subjects receiving therapy for a median of 10 months. while the most frequently reported adverse events were muscle spasms, dysgeusia, diarrhea, and alopecia, no secondary malignancies, like cscc, were recorded.13 after fda approval, an openlabel study included 119 patients with bcc receiving vismodegib for a median duration of 5.5 months. adverse events with a median safety follow-up of 6.5 months were tabulated. one patient developed recurrence of a prior cscc, however, this adverse event was not deemed to be related to vismodegib.3 in the years following vismodegib’s approval, several studies reported8, 9, 10, 11, 14, 15, 19, 20, 24 cscc development after vismodegib initiation. in one patient who developed cscc 13 months after vismodegib initiation, genetic testing from the primary bcc and the subsequent cscc revealed shared tumor drivers, suggesting vismodegib may induce a phenotypic change from bcc to cscc. 11 a retrospective study of 19 patients with bcc assessing vismodegib’s ability to induce metatypical change of bcc demonstrated metatypical change in 5 cases and squamous change in 2 cases.25 a retrospective cohort study evaluated vismodegib and cscc development in 180 patients, separated into two groups based on exposure (55 patients) or lack of exposure (125 patients) to vismodegib.2 the overall rate of subsequent non-bcc cancers was higher in the non-exposed group than in the exposed group. however, a cox proportional hazards regression analysis revealed an increased risk of non-bcc cancer, most frequently cscc, in the exposed group compared to the control group (hazard ratio: 8.12; 95% confidence interval, 3.39-11.96, p<0.001).2 invasive cscc was more common than in-situ cscc, suggesting vismodegib may potentiate more aggressive cscc.2 the median time between initial therapy and diagnosis of secondary malignancy was 0.9 years (ranging from 2 weeks to 2.7 years). however, whether csccs emerging just two weeks after initiation could be attributed to vismodegib remains controversial.6 additionally, the results of this study have not been reproducible. methods results skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 494 figure 1. study identification and selection using the preferred reporting items for systematic reviews and meta-analyses (prisma) flow diagram. *records excluded due to topic or lack of applicability to the research question. skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 495 table 1. of the 25 articles included, 14 reported patient outcome data and statistics on cscc development after vismodegib treatment. of the 2576 patients included, there were 197 csccs reported. the duration of vismodegib treatment until cscc development ranged from 2 weeks to 2.7 years. median duration of treatment was 3 months. author date published article type total patients in study number of csccs reported duration of vismodegib treatment until cscc diagnosis key findings axelson et al 2013 phase ii 138 0 no reported cases of cscc chang et al 2013 open-label, multicenter study 119 1 <30 days one patient died due to a recurrence of previously treated cscc. presumed to be unrelated to therapy with vismodegib aasi et al 2013 case report 2 2 2 weeks, 7 weeks 2 patients treated with vismodegib developed new onset keratoacanthomas 2 weeks and 7 weeks after treatment iarrobino et al 2013 case report 1 1 not available biopsy of previous bcc treated with vismodegib after recurrence demonstrated scc zhu et al 2014 case report 2 2 4 months, 2.5years invasive cscc developed near bcc after 4 months. cscc developed at the primary site after 2.5 years of treatment. orouji et al 2014 case report 1 1 4 weeks several distant sites of moderate to highly differentiated cscc saintes et al 2014 case report 3 3 1 to 3 months 3 patients treated with vismodegib developed cscc. the lesions were biopsied due to poor treatment response ransohoff et al 2015 case report 1 1 13 months 1 patient with metastatic bcc treated with vismodegib developed cscc 13 months after treatment. genetic testing revealed the scc shared tumor drivers with the original lesion. poulalhon et al 2015 case report 1 1 4 months 1 patient with bcc and adjacent scc treated with vismodegib had progression of bcc lesion after four months. biopsy revealed invasive scc. mohan et al 2016 case-control study 180 66 2 weeks to 2.7 years vismodegib was associated with an increased risk of cscc in exposed versus those not exposed (hazard ratio: 8.12;95% confidence interval, 3.39-11.96, p<0.001) bhuatani et al 2017 retrospective cohort study 1675 73 1 year vismodegib was not associated with an increased risk of scc compared to standard bcc therapy after a year (hazard ratio: 0.57; 95% confidence interval, 0.28-1.16). feigenbaum et al 2017 case report 1 1 3 months 1 patient with 4 bccs treated with vismodegib developed infiltrative bcc with squamous differentiation. bancalari et al 2019 retrospective study 19 0 biopsy samples of bccs before, during and after treatment with vismodegib. 5 cases had metatypical change after treatment, and 2 cases had squamous change. no cases of squamous cell carcinoma were observed. sekulic et al 2022 prospective, multicenter, observational registry study 433 45 not available, median follow up of 23.6 months rates of csccs did not significantly differ between those treated with vismodegib and not treated. the exposure-adjusted-incidence rate of cscc after vismodegib exposure was 0.06 cases per patientyear compared to 0.07 cases per patient-year in the non-exposed group. skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 496 two large, multicenter studies1,4, one a retrospective cohort and the other a prospective observational registry, found that the risk of cscc after exposure to vismodegib use was comparable to the control groups with no exposure. in 2017, a retrospective cohort study of 1675 patients compared patients treated with vismodegib from phase i and ii clinical trials and patients who received standard surgical treatment for bcc. multivariate proportional hazards analysis did not reveal an increased risk of cscc with vismodegib use (hazard ratio: 0.57; 95% confidence interval, 0.28-1.16).1 in 2022, a prospective, multi-center observational registry analyzed over 500 patients with locally advanced bcc not treated with vismodegib. overall, the study found comparable rates of cscc between the vismodegib-treatment group (12% of patients developed cscc, exposureincidence rate of 0.06 cases per year) and the non-vismodegib treatment group (12% of patients developed cscc, exposureincidence rate of 0.07 cases per year).4 since vismodegib’s approval by the fda for the treatment of invasive or metastatic bcc, there have been anecdotal concerns that vismodegib can induce cscc. while a retrospective cohort study2 seemed to verify that vismodegib is associated with an increased risk of cscc, these results have not been reproduced. based on the available findings, vismodegib does not appear to increase the risk for subsequent cscc. it is plausible that patients who have already developed bcc are at risk of other skin cancers, like cscc, due to shared risk factors. as an hhi, vismodegib’s role in cscc development may be due to select tumor cells circumventing the hedgehog pathway, and instead utilizing other growth pathways, including ras/mapk.2,18 further investigation has demonstrated the importance of cilium in tumor pathway switching, with a decrease in cilium gene expression in bccs resistant to hhis. this results in low hedgehog pathway activation and an increase in ras/mapk pathway activation.16,17 limitations of this review include only using two databases to search for articles and the limited number of published articles that address the research question. the quality of certain study types included in the review, such as case reports, is another limitation of this article. the current data available on the relationship between vismodegib use and the subsequent development of cscc is not definitive and does not demonstrate causality. with a high efficacy rate in the treatment of bccs not amenable to surgical resection or radiation, vismodegib should not be avoided due to concerns of causing secondary cutaneous neoplasms. however, the data available does suggest that patients treated for bcc with vismodegib should be closely monitored by dermatologists to evaluate lesions for response to treatment, changes, or signs of progression. when in doubt, the lesion should always be re-biopsied. additional large-scale, prospective, multi-center studies should be conducted to definitively evaluate the risk of vismodegib use in the development of cscc. conflict of interest disclosures: none funding: none corresponding author: discussion conclusion skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 497 jenne p. ingrassia, ba 40 sunshine cottage valhalla, ny, 10504 phone: 914-594-4000 fax: 914-594-3752 email: jenneingrassia@gmail.com references: 1. bhutani t, abrouk m, sima cs, et al. risk of cutaneous squamous cell carcinoma after treatment of basal cell carcinoma with vismodegib. j am acad dermatol. 2017;77(4):713-718. doi:10.1016/j.jaad.2017.03.038 2. mohan sv, chang j, li s, henry as, wood dj, chang al. increased risk of cutaneous squamous cell carcinoma after vismodegib therapy for basal cell carcinoma. jama dermatol. 2016;152(5):527-532. doi:10.1001/jamadermatol.2015.4330 3. chang al, solomon ja, hainsworth jd, et al. expanded access study of patients with advanced basal cell carcinoma treated with the hedgehog pathway inhibitor, vismodegib. j am acad dermatol. 2014;70(1):60-69. doi:10.1016/j.jaad.2013.09.012 4. sekulic a, yoo s, kudchadkar r, et al. realworld assessment and treatment of locally advanced basal cell carcinoma: findings from the regisonic disease registry. plos one. 2022;17(1):e0262151. published 2022 jan 14. doi:10.1371/journal.pone.0262151 5. li s, chang al. study on the risk of cutaneous squamous cell carcinoma after vismodegib therapy for basal cell carcinoma-reply. jama dermatol. 2016;152(10):1173. doi:10.1001/jamadermatol.2016.2429 6. puig s, sampogna f, tejera-vaquerizo a. study on the risk of cutaneous squamous cell carcinoma after vismodegib therapy for basal cell carcinoma: not a case-control study. jama dermatol. 2016;152(10):1172-1173. doi:10.1001/jamadermatol.2016.2428 7. gjersvik p. study on the risk of cutaneous squamous cell carcinoma after vismodegib therapy for basal cell carcinoma: not a casecontrol study. jama dermatol. 2016;152(10):1172. doi:10.1001/jamadermatol.2016.2427 8. saintes c, saint-jean m, brocard a, et al. development of squamous cell carcinoma into basal cell carcinoma under treatment with vismodegib. j eur acad dermatol venereol. 2015;29(5):1006-1009. doi:10.1111/jdv.12526 9. iarrobino a, messina jl, kudchadkar r, sondak vk. emergence of a squamous cell carcinoma phenotype following treatment of metastatic basal cell carcinoma with vismodegib. j am acad dermatol. 2013;69(1):e33-e34. doi:10.1016/j.jaad.2013.01.023 10. poulalhon n, dalle s, balme b, thomas l. fastgrowing cutaneous squamous cell carcinoma in a patient treated with vismodegib. dermatology. 2015;230(2):101-104. doi:10.1159/000368350 11. ransohoff kj, tang jy, sarin ky. squamous change in basal-cell carcinoma with drug resistance. n engl j med. 2015;373(11):10791082. doi:10.1056/nejmc1504261 12. rübben a, hilgers rd, leverkus m. hedgehog blockade for basal cell carcinoma: coming at a (secondary neoplastic) price. jama dermatol. 2016;152(5):521-523. doi:10.1001/jamadermatol.2015.5239 13. axelson m, liu k, jiang x, et al. u.s. food and drug administration approval: vismodegib for recurrent, locally advanced, or metastatic basal cell carcinoma. clin cancer res. 2013;19(9):2289-2293. doi:10.1158/10780432.ccr-12-1956 14. orouji a, goerdt s, utikal j, leverkus m. multiple highly and moderately differentiated squamous cell carcinomas of the skin during vismodegib treatment of inoperable basal cell carcinoma. br j dermatol. 2014;171(2):431-433. doi:10.1111/bjd.12840 15. aasi s, silkiss r, tang jy, et al. new onset of keratoacanthomas after vismodegib treatment for locally advanced basal cell carcinomas: a report of 2 cases. jama dermatol. 2013;149(2):242243. doi:10.1001/jamadermatol.2013.1798 16. kuonen f, huskey ne, shankar g, et al. loss of primary cilia drives switching from hedgehog to ras/mapk pathway in resistant basal cell carcinoma. j invest dermatol. 2019;139(7):14391448. doi:10.1016/j.jid.2018.11.035 17. otsuka a, dreier j, cheng pf, et al. hedgehog pathway inhibitors promote adaptive immune responses in basal cell carcinoma. clin cancer res. 2015;21(6):1289-1297. doi:10.1158/10780432.ccr-14-2110 18. zhao x, ponomaryov t, ornell kj, et al. ras/mapk activation drives resistance to smo inhibition, metastasis, and tumor evolution in shh pathway-dependent tumors. cancer res. 2015;75(17):3623-3635. doi:10.1158/00085472.can-14-2999-t 19. lee jj, kroshinsky d, hoang mp. cutaneous reactions to targeted therapy. am j dermatopathol. 2017;39(2):67-82. doi:10.1097/dad.0000000000000504 mailto:jenneingrassia@gmail.com skin november 2022 volume 6 issue 6 (c) 2022 the authors. published by the national society for cutaneous medicine. 498 20. zhu ga, sundram u, chang al. two different scenarios of squamous cell carcinoma within advanced basal cell carcinomas: cases illustrating the importance of serial biopsy during vismodegib usage. jama dermatol. 2014;150(9):970-973. doi:10.1001/jamadermatol.2014.583 21. chang als. commentary on development of basal cell carcinoma with squamous differentiation during vismodegib treatment. dermatol surg. 2017;43(7):991-992. doi:10.1097/dss.0000000000001059 22. danhof r, lewis k, brown m. small molecule inhibitors of the hedgehog pathway in the treatment of basal cell carcinoma of the skin. am j clin dermatol. 2018;19(2):195-207. doi:10.1007/s40257-017-0319-4 23. li s, chang al. study on the risk of cutaneous squamous cell carcinoma after vismodegib therapy for basal cell carcinoma-reply. jama dermatol. 2016;152(10):1173. doi:10.1001/jamadermatol.2016.2429 24. feigenbaum l, scott bl, moye ms, nijhawan ri. development of basal cell carcinoma with squamous differentiation during vismodegib treatment. dermatol surg. 2017;43(7):989-991. doi:10.1097/dss.0000000000001012 25. bancalari b, llombart b, serra-guillén c, et al. histologic changes during treatment with vismodegib in locally advanced basal cell carcinoma: a series of 19 cases. am j dermatopathol. 2019;41(10):711-717. doi:10.1097/dad.0000000000001384 tapinarof cream 1% once daily for the treatment of extensive atopic dermatitis in adolescents and children: 4-week maximal-use trial amy paller,1 adelaide a. hebert,2 john e. jett,3 philip m. brown,3 david s. rubenstein,3 stephen c. piscitelli3 1northwestern university feinberg school of medicine, chicago, il, usa; 2mcgovern school of medicine and children’s memorial hermann hospital, uthealth mcgovern, houston, tx, usa; 3dermavant sciences, inc., morrisville, nc, usa introduction ■ atopic dermatitis (ad) is a chronic, relapsing and remitting inflammatory skin disease, characterized by intense pruritus and eczematous lesions. ad can substantially impact patients’ sleep and quality of life1–4 ■ there is a need for efficacious, non-steroidal topical therapies for ad, without restrictions relating to duration, extent of use, and application sites ■ tapinarof (vtama®; dermavant sciences, inc., usa) is a first-in-class, non-steroidal, topical aryl hydrocarbon receptor (ahr) agonist approved by the food and drug administration for the treatment of plaque psoriasis in adults, and under investigation for the treatment of plaque psoriasis in children down to 2 years of age and for ad in adults and children down to 2 years of age5 ■ tapinarof cream 1% once daily (qd) demonstrated significant efficacy versus vehicle and was well tolerated in adults with mild to severe plaque psoriasis in two identical, 12-week, phase 3 trials, psoaring 1 (nct03956355) and psoaring 2 (nct03983980)6 – efficacy continued to improve beyond the 12-week trials in psoaring 3 (nct04053387), the long-term extension trial7 ■ tapinarof specifically binds to and activates the ahr, a ligand-dependent transcription factor. this leads to downregulation of inflammatory th2 cytokines (including interleukin [il] -4, il-5, and il-13), increase in expression of skin barrier proteins related to keratinocyte differentiation (including filaggrin, loricrin, and involucrin), and antioxidant activity8–12 (figure 1) figure 1. potential mechanisms of action of tapinarof in atopic dermatitis *demonstrated in vitro. †demonstrated in mouse models. ‡demonstrated ex vivo. ahr, aryl hydrocarbon receptor; arnt, aryl hydrocarbon receptor nuclear translocator; il, interleukin; nrf2, nuclear factor erythroid 2-related factor 2; ros, reactive oxygen species; tap, tapinarof. ■ tapinarof cream 1% qd demonstrated significant efficacy versus vehicle and was well tolerated in adults and adolescents with moderate to severe ad in a 12-week phase 2b trial (nct02564055)13,14 – efficacy was generally maintained through the last trial visit, 4 weeks after completing treatment13,14 ■ in a phase 1 pharmacokinetics (pk) evaluation of tapinarof cream 1% in adults (n=6) with moderate to severe ad, there were low levels of systemic absorption that decreased from baseline to day 21 of assessment (mean 1.2 ng [10–9]/ml [day 1] and 0.15 ng/ml [day 21])15 ■ tapinarof cream 1% has also been assessed in a 4-week, maximal-use pk trial in adults with extensive plaque psoriasis; tapinarof was well tolerated with limited systemic exposure, even in patients with up to 46% body surface area (bsa) affected16 objectives ■ to present the 4-week, maximal-use ad trial design and patient baseline characteristics ■ to assess the safety, tolerability, pk, and efficacy of tapinarof cream 1% qd in adolescents and children with extensive ad in the 4-week, maximal-use trial methods trial design ■ in this phase 2a, multicenter, open-label trial (nct05186805), adolescents and children with extensive ad will receive tapinarof cream 1% qd for 27 days (figure 2) ■ patients or caregivers will be instructed to apply a thin layer of tapinarof cream, sufficient to cover each lesion ■ tapinarof pk will be assessed at days 1 (baseline) and 28 – the screening blood sample will be used for baseline pre-dose pk assessment if the patient is enrolled ■ key inclusion and exclusion criteria are shown in table 1 ■ eligible patients completing this trial will have the option to enroll in an open-label, long-term extension trial (nct05142774) to receive up to an additional 48 weeks of tapinarof treatment figure 2. maximal-use pk trial design in adolescents and children with ad ad, atopic dermatitis; pk, pharmacokinetics; qd, once daily. table 1. key inclusion and exclusion criteria inclusion criteria exclusion criteria males and females aged 2–17 years significant dermatologic or inflammatory condition and concurrent skin lesions in the treatment area or pruritus due to conditions other than ad a clinical diagnosis of ad by hanifin and rajka criteria17 patients who would not be considered suitable for topical therapy %bsa involvement ≥25% for adolescents (12–17 years) or ≥35% for children (2–11 years) use of any prohibited medication or procedure within the indicated period before the baseline visit a viga-adtm score of ≥3 at screening and baseline (pre-dosing) history of sensitivity to the trial medications ad present for ≥6 months for patients aged 6–17 years or 3 months for patients aged 2–5 years previous known participation in a clinical trial with tapinarof ad, atopic dermatitis; bsa, body surface area; viga-adtm, validated investigator global assessment for atopic dermatitistm. primary endpoints ■ incidence, frequency, and nature of adverse events (aes) and serious aes ■ change from baseline in laboratory values and vital signs ■ mean investigator-assessed local tolerability scale scores by visit (overall and sensitive areas) ■ tapinarof plasma pk parameters on day 1, including: – area under the plasma concentration versus time curve from baseline to the last quantifiable concentration (auc 0–last ) – maximum plasma concentration (c max ) – time to maximum plasma concentration (t max ) – time of last quantifiable concentration (t last ) ■ tapinarof plasma concentration on day 28 secondary endpoints ■ change in validated investigator global assessment for atopic dermatitistm (viga-adtm) score by visit ■ proportion of patients with a viga-adtm score of clear (0) or almost clear (1) by visit ■ proportion of patients with ≥50%, ≥75%, and ≥90% improvement in eczema area and severity index (easi) score by visit ■ mean change and percent change in easi score by visit ■ mean change and percent change in %bsa affected by visit ■ proportion of patients with a baseline peak pruritus-numeric rating scale (pp-nrs) score of ≥4 who achieve a ≥4-point reduction in pp-nrs score by visit – proportion of patients ≥12 years old with a baseline pp-nrs score ≥4 who achieve a ≥4-point reduction in pp-nrs score by visit – proportion of patients 2–12 years old with a baseline pp-nrs score ≥4 who achieve a ≥4-point reduction in pp-nrs score by visit – mean change in pp-nrs score at each visit by age group statistical analyses ■ safety analyses will include all patients who received at least one application of tapinarof ■ analyses of efficacy endpoints will be based upon the safety population results baseline patient demographics and disease characteristics ■ overall, 36 patients were enrolled at nine sites in the us and canada ■ patients’ baseline demographics and disease characteristics are shown in table 2 – equal proportions of patients (33.3% [12/36]) were young children (2–6 years), children (7–11 years), and adolescents (12–17 years) – most patients (77.8%) across the three groups had a viga-adtm score of 3 (moderate) – overall mean (standard deviation [sd]) easi score was 23.8 (9.2), with a range of 8.2–49.6 indicating moderate to severe ad – overall mean (sd) %bsa affected was 42.8% (15.1%), with a range of 26%–90% table 2. baseline demographics and disease characteristics tapinarof cream 1% qd young children 2–6 years (n=12) children 7–11 years (n=12) adolescents 12–17 years (n=12) overall (n=36) age, years, mean (sd) 3.7 (1.4) 8.2 (1.4) 14.8 (1.8) 8.9 (4.9) male, n (%) 9 (75.0) 7 (58.3) 8 (66.7) 24 (66.7) viga-adtm of 3 (moderate), n (%) 8 (66.7) 9 (75.0) 11 (91.7) 28 (77.8) viga-adtm of 4 (severe), n (%) 4 (33.3) 3 (25.0) 1 (8.3) 8 (22.2) easi, mean (sd) 30.2 (8.6) 21.0 (10.0) 20.3 (5.5) 23.8 (9.2) bsa affected, %, mean (sd) 52.4 (19.1) 42.0 (10.0) 33.9 (8.6) 42.8 (15.1) bsa, body surface area; easi, eczema area and severity index; qd, once daily; sd, standard deviation; viga-adtm, validated investigator global assessment for atopic dermatitistm. conclusions ■ in a phase 2b trial, tapinarof cream 1% qd demonstrated significant efficacy versus vehicle and was well tolerated in adolescents and adults with moderate to severe ad13,14 ■ tapinarof cream 1% has shown minimal systemic absorption in adults with ad or psoriasis, even with extensive bsa affected of up to 46%15,16 ■ this maximal-use pk trial will assess the safety, tolerability, pk, and efficacy of tapinarof cream 1% qd in 36 adolescents and children down to 2 years of age with extensive, moderate to severe ad ■ in addition, tapinarof cream 1% qd is being evaluated for the treatment of ad in adults and children down to 2 years of age in three phase 3 clinical trials (adoring 1 [nct05014568], adoring 2 [nct05032859], and adoring 3 [nct05142774]) references 1. weidinger s and novak n. lancet. 2016;387:1109–1122. 2. bieber t. n engl j med. 2008;358:1483–1494. 3. carroll cl, et al. pediatr dermatol. 2005;22:192–199. 4. lewis-jones s. int j clin pract. 2006;60:984–992. 5. dermavant sciences. vtama (tapinarof) cream, 1%: us prescribing information. 2022. https://www.vtama.com/docs/dmvt_vtama_pi.pdf. accessed july 2022. 6. lebwohl m, et al. n engl j med. 2021;385:2219–2229. 7. strober b, et al. j am acad dermatol. 2022. https://doi.org/10.1016/j.jaad.2022.06.1171. 8. bissonnette r, et al. j am acad dermatol. 2021;84:1059–1067. 9. dermavant dof [dmvt-505 th2 polarization; apr 2015]. 10. dermavant dof [dmvt-505 ad mouse model; oct 2016]. 11. smith sh, et al. j invest dermatol. 2017;137:2110–2119. 12. kim be, et al. allergy asthma immunol res. 2018;10:207– 215. 13. peppers j, et al. j am acad dermatol. 2019;80:89–98. 14. paller a, et al. j am acad dermatol. 2021;84:632–638. 15. bissonnette r, et al. clin pharmacol drug dev. 2018;7:524–531. 16. jett je, et al. am j clin dermatol. 2022;23:83–91. 17. hanifin jm and rajka g. acta dermatovener (stockholm) suppl. 1980;92:44–47. acknowledgments this trial was funded by dermavant sciences, inc. the authors thank the participating investigators, patients and their families, and colleagues involved in the conduct of the trial. a.p. is an investigator (without personal compensation) for abbvie, anaptysbio, dermavant sciences inc., eli lilly, incyte, janssen, krystal, regeneron, and ucb pharma, a consultant (with honoraria) for abbvie, acrotech, almirall, amgen, amryt, arcutis, arena, azitra, biocryst, biomx, boehringer ingelheim, botanix, bridgebio, castle biosciences, catawba, eli lilly, exicure, gilead, incyte, janssen, kamari, leo, novartis, pfizer, pierre fabre, rapt, regeneron, sanofi/genzyme, seanergy, ucb pharma, union, and on the data safety monitoring board for abbvie, abeona, bausch, bristol myers squibb, galderma, inmed, and novan. a.a.h. has received grants/ honoraria/ research support from abbvie, almirall, arcutis, dermavant sciences inc., gsk (as part of a data safety monitoring board), incyte, leo pharma, mayne, novan, and verrica. j.e.j., p.m.b., d.s.r., and s.c.p. are employees of dermavant sciences, inc., with stock options. editorial and medical writing support under the guidance of the authors was provided by apothecom, uk, and was funded by dermavant sciences, inc. in accordance with good publication practice (gpp3) guidelines (ann intern med. 2015;163:461–464). contact dr paller at apaller@nm.org with questions or comments. open-label treatment (27 days) adolescents and children�with ad screening for up to 30 days tapinarof cream 1% qd follow-up visit ~7 days after end of treatment powerpoint presentation winter clinical dermatology conference hawaii • jan. 13 – 18th, 2023 • moderate-to-severe atopic dermatitis (ad) has a significant negative impact on quality of life in adults and adolescents1,2 • despite being eligible for advanced systemic therapy (ast) due to uncontrolled moderate or severe ad, many adolescent patients do not progress to ast • this study characterizes the population of adolescent (age 12-17) patients with moderate-to-severe ad who were ast-treated to those who were not ast-treated (ast-naïve) to better understand progression to ast-usage in these patients. results ast-usage • less than 50% of patients were treated with an ast among the 91 adolescents who met study criteria: 55% (n=50) were ast-naïve, and 45% (n=41) were ast-treated • all ast treatment was with dupilumab, no upadacitinib usage reported • of 44 physicians, 36 (82%) were dermatologists and 8 (18%) allergists in this analysis. all 41 ast-treated patients (100%) saw a dermatologist, and none saw allergist (0%), of the ast-naïve 42 (84%) saw a dermatologist and 8 (16%) an allergist (p=0.008) ast-naïve vs. ast-treated descriptive analysis • no significant differences were observed between ast-usage groups for age, gender, race, insurance type, treatment center, viga-ad, cdlqi, poem, promis depression, promis anxiety, or prior use of topical therapies at enrollment • ast-treated had significantly higher median enrollment severity on two measures of disease severity • bsa (35% vs 15%, p=0.0076) • viga-ad x bsa (105 vs 48, p<0.0066) • ast-treated had a significantly higher po-scorad at enrollment vs ast-naïve (45.8 vs. 31.1, p<0.03) ast-naïve vs ast-treated multivariate analysis • in multivariate analysis controlling for sex, age, insurance, and race, only higher bsa at enrollment was associated with ast-usage • bsa of 5% or=1.09 (1.01-1.19) • bsa of 10% or = 1.2 (1.01-1.42) • bsa of 20% or = 1.43 (1.02-2.01) 1 rady children’s hospital, san diego, ca 2 university of california san diego, san diego, ca 3 target rwe, durham, nc 4 leo pharma inc., madison, nj 5 george washington school of medicine, washington dc 6 university of lübeck, lübeck germany use of advanced systemic therapy in adolescent patients with moderate-to-severe atopic dermatitis in the target-derm registry haft m1,2, knapp k3, claxton a4, hernandez b3, balu s4, schneider s4, silverberg j5, thaci d6, eichenfield l1,2 on behalf of target-derm investigators conclusion • more than half of the patients with considerable disease severity and who experienced negative qol from moderate-to-severe ad were not prescribed ast • compared to ast-naïve patients, descriptive analysis showed that the asttreated were slightly more severe as indicated by significantly higher baseline bsa, higher viga-adxbsa, and higher po-scorad at enrollment. • in multivariate analysis to adjust for baseline characteristics, higher bsa at enrollment was significantly associated with use of an ast. • longitudinal follow-up is needed to determine the outcomes associated with these treatment patterns to evolve therapeutic interventions and outcomes in these adolescent patients. variables of interest: • patient demographics • site and physician type • prior and concomitant topical ad therapy (any, calcineurin inhibitor, corticosteroid, phosphodiesterase) disease severity measures: • viga-ad (scores 0-4) • total body surface area (bsa) (score 0-100%) • viga-ad x bsa (score 0-400) patient population: • adolescent (12-17 years) • moderate or severe ad defined as a score of 3 or 4 on the validated investigator global assessment ad (viga-ad) at enrollment • treatment history: had prior exposure to at least one of the following: topical corticosteroid, systemic corticosteroid, immunomodulator or phototherapy • had at least 1 post-enrollment visit • excluded were clinical trial patients and any patient treated with an ast prior to enrollment methods target-derm ad all patients n=2549 age 12-17 (n=327) met treatment history criteria (n=186) study population n=91 • ast-naïve (n=50) • ast-treated (n=41) ast-treated n=41 • moderate n=23 • severe n=18 ast-naïve n=50 • moderate n=37 • severe n=13 excluded: ast users prior to enrollment (n=34) and clinical trial patients (n=0) had 1+ follow-up visits (n=125) moderate or severe ad: viga-ad of 3 or 4 (n=191) figure 1. patient disposition acknowledgements and disclosures target rwe communities are collaborations among academic & community investigators, the pharmaceutical industry, and patient community advocates. target rwe communities are sponsored by target pharmasolutions inc (d.b.a., target rwe). the authors would like to thank all the investigators, participants, and research staff associated with target-derm ad. clinicaltrials.gov identifier: nct03661866. leo pharma is a target rwe industry partner which subscribes for data access. mh has no financial disclosures. kk and bh are employees of target rwe. ac, sb, and ss are employees of leo pharma. js received honoraria as a consultant and/or advisory board member for abbvie, afyx, aobiome, arena, asana, aslan, biomx, biosion, bluefin, bodewell, boehringer-ingelheim, cara, castle biosciences, celgene, connect biopharma, dermavant, dermira, dermtech, eli lilly, galderma, glaxosmithkline, incyte, kiniksa, leo pharma, luna, menlo, novartis, optum, pfizer, rapt, regeneron, sanofi-genzyme, shaperon, sidekick health, union; speaker for abbvie, eli lilly, leo pharma, pfizer, regeneron, sanofi-genzyme; institution received grants from galderma, pfizer; dt abbvie, almirall, amgen, biogen idec, boehringer ingelheim, dermira, eli lilly, galderma, gsk, janssen-cilag, leo-pharma, novartis, pfizer, regeneron, roche, sandoz-hexal, sanofi, and ucb; consultant: abbvie, almirall, amgen, dignity, galapagos, leo pharma, maruho, mitsubishi, novartis, sanofi, pfizer, regeneron, target-solution, and ucb; lectures: abbvie, almirall, amgen, janssen, leo pharma, msd, novartis, pfizer, roche-posay, sandoz-hexal, sanofi, and ucb; scientific advisory board: abbvie, boehringer ingelheim, eli lilly, galapagos, janssen-cilag, leo pharma, morphosis, novartis, pfizer, regeneron, sanofi, and ucb; le has served as a scientific adviser, consultant, and/or clinical study investigator for abbvie, almirall, arcutis, arena, aslan, dermavant, eli lilly, forté, galderma, incyte, janssen, leo pharma, novartis, ortho, otsuka, pfizer, regeneron, sanofi genzyme fig 2a. patient characteristics by ast-usage patient reported outcomes: • cdlqi: children’s dermatology life quality index (scores 0-30) • poem: patient-oriented eczema measure (scores 0-28) • po-scorad: patient-oriented scoring atopic dermatitis (scores 0-103) • patient-reported outcomes measurement information system (promis) depression (scores 41.0-79.4) and promis anxiety (scores 40.9-85.2) references 1. nutten, s., atopic dermatitis: global epidemiology and risk factors. ann nutr metab, 2015. 66 suppl 1: p. 8-16. 2. ad langan sm, irvine ad, weidinger s. lancet. 2020 aug 1;396(10247):345-360. 3. abuabara, k. international observational atopic dermatitis cohort to follow natural history and treatment course: targetderm ad study design and rational bmj open 2020;10:e0399282020. figure 3. factors associated with ast-treatment. significant values are in blue. • target-derm ad is an ongoing, longitudinal, observational study of adult and adolescent dermatology patients managed in clinical practice at 32 community (n=15) or academic (n=17) sites in the united states; first patients were enrolled in jan. 25th, 2019. 3 the data cutoff for this analysis was aug 11, 2022. • ast is defined as dupilumab (adolescent indication approved 05/262020) and upadacitinib (adolescent indication approved 01/11/22) • , approved treatments for adolescents with moderate-to-severe ad. • patients were classified into two unique ast usage groups: ast-treated (any ast usage at or after enrollment) or ast-naïve (no ast usage at or after enrollment). • data was analyzed descriptively. the association between clinical/pros and astusage was estimated by multivariate binary logistic regression controlling for age, race, gender, insurance, and site type. • all analysis was conducted on enrollment (baseline) data introduction figure 2b. median clinical and pro scores by ast-usage 0 20 40 60 80 100 120 b s a ( % ) v ig a -a d x b s a p o -s c o r a d p o e m p r o m is d e p re ss io n (t -s co re ) p r o m is a n xi e ty (t -s co re ) m e d ia n s co re ast-naïve ast-treated 0.0% 10.0% 20.0% 30.0% 40.0% 50.0% 60.0% 70.0% 80.0% 90.0% 100.0% f e m a le ( % ) h is p a n ic /l a ti n o n h w h it e n h b la ck a si a n o th e r/ n o t re p o rt e d m o d e ra te s e ve re a n y p ri o r to p ic a l tr e a tm e n t p ri o r ca lc in e u ri n i n h ib it o r tr e a tm e n t p ri o r co rt ic o st e ro id tr e a tm e n t p ri o r p h o sp h o d ie st e ra se in h ib it o r tr e a tm e n t a ll e rg is t d e rm a to lo g is t m e d ic a id p ri va te u n in su re d a ca d e m ic c o m m u n it y sex race/ethnicity viga topical medication treatment specialty insurance site type p e rc e n ta g e ast-naïve ast-treated in addition to the covariates listed above, other factors were considered, but were not found to be significant; data not shown or (95% ci) 0.98 (0.4 – 2.43) 1.17 (0.44 – 3.11) 0.88 (0.37 – 2.12) 0.68 (0.27 – 1.75) 1.17 (0.46 – 2.98) 1.09 (1.01 – 1.19) 1.2 (1.01 – 1.42) 1.43 (1.02 – 2.01) age: 15-17 vs. 12-14 race: non nh-white vs nh-white sex: male vs. female insurance: non-private vs private site type: academic vs community increase in 5% of bsa increase in 10% of bsa increase in 20% of bsa p=0.0076 p=0.0066 p=0.0241 __p=0.008__ conclusions • both fmx101 4% and fmx103 1.5% were shown to deliver high concentrations of minocycline to the epidermis and sebaceous appendage, while much lower concentrations were delivered to the dermis skin layer • there were no statistical differences between fmx101 and fmx103 in the amount of minocycline that permeated across the skin into the receptor solution over 12 hours • approximately half of minocycline delivered to the epidermis was recovered from the sebaceous appendages limitations • derived calculations based on ex vivo skin penetration studies are intended to approximate, but may not precisely reflect, the permeation and penetration of active molecules in patients with a dermatologic condition results ex vivo assessment of fmx101 & fmx103 human skin permeation and penetration russell elliott, phd1, gary lawrence1, yohan hazot1, lenny margulis1, vassilis stakias, pharmd1, iain stuart, phd1 1foamix pharmaceuticals inc., bridgewater, nj, us figure 3: penetration: distribution of minocycline in the sebaceous appendage * approximately half of minocycline delivered to the epidermis was recovered from the sebaceous appendages for both formulations • acne vulgaris is a prevalent, chronic, inflammatory skin disorder affecting approximately 85% of the population at some point in their lifetime1 • oral antibiotics, such as minocycline and doxycycline, are mainstays of treatment for moderate-to-severe acne but are associated with potentially serious systemic side effects2 • two novel foam formulations of minocycline, fmx101 4% and fmx103 1.5% differing only in their antibiotic concentration, have been developed for potential use in acne vulgaris and papulopustular rosacea • understanding the permeation and penetration of active agent into skin structures, particularly the epidermis, dermis, and sebaceous appendage, is critical to characterizing these formulations • an ex vivo permeation and penetration experiment using flow through diffusion cells (medflux-ht™) was performed to assess foam formulations developed by foamix pharmaceuticals inc. • the ex vivo experiments assessed two active formulations, fmx101 4% and fmx103 1.5%, and 2 placebo formulations • minocycline penetration was examined by extracting drug from epidermis (n=5), dermis (n=5), and the sebaceous appendage (n=5) • full scale skin permeation and penetration investigations were performed (n=5, one skin donor) ex vivo assessment of drug delivery across human skin to the sebaceous appendages assessed using a flow-through diffusion cell • the flow-through diffusion cell (figure 1) was used to assess drug delivery across human skin and to the sebaceous appendages •����human�skin�from�a�single�donor�was�initially�stored�at�−80⁰�c� and thawed at room temperature. next, the human skin was placed between the donor compartment and receptor compartment of the diffusion cell • to perform an ex vivo permeation and penetration assessment for 2 prototype foam formulations of minocycline, fmx101 4% and fmx103 1.5% disclosures this study was funded by foamix pharmaceuticals, inc. acknowledgment editorial support was provided by scient healthcare communications. penetration: distribution of minocycline in the skin and in plasma (tissue distribution) • fmx101 delivered 3539 ng of minocycline to the sebaceous appendages (0.67% of applied dose) and fmx103 delivered 909 ng of minocycline to the sebaceous appendages (0.52% of applied dose) (p <0.001) • after a single application of either fmx101 4% or fmx103 1.5%, the concentration of minocycline in the skin was as follows: figure 2: concentrations of minocycline in the skin and plasma * these data were converted into minocycline concentrations (µg/ml) accounting for average weight and density of skin, volume of sebaceous appendages, and cellular volume corrections. post-hoc data analysis for tissue and appendage concentrations • in order to convert the amounts of minocycline in epidermis and dermis to concentrations on a volume of skin (ie, per ml), the following assumptions were made: • historical average weights from over 438 skin samples were used. the average weight of epidermis was assumed to be 8.6 mg and the average weight of dermis was assumed to be 96 mg • the density of skin was assumed to be 1 g/ml • the amount of drug in the sebaceous appendage (amount of drug per volume of appendage) was calculated using the following assumption: • the volume of the infundibula (sebaceous appendage separated by cyanoacrylate glue) was calculated based on a volume of 0.09 mm3 (lademann et. al, section 10). this was calculated as the average of the volume of the infundibula on the forehead (0.19 mm3) and that on the forearm (0.01 mm3) as no determination of the volume of the infundibula on the abdomen was conducted quantification of minocycline •���the�lc-ms/ms�analytical�method�was�developed�and�used� to determine amount of drug delivered to the sebaceous appendages, dermis and epidermis • this was determined to be a sensitive quantification of minocycline from receptor solution and skin tissue homogenates lc-ms/ms=liquid�chromatography�–�mass�spectrometry/mass�spectrometry 1. thiboutot dm, dréno b, abanmi a, et al. practical management of acne for clinicians: an international consensus from the global alliance to improve outcomes in acne. j am acad dermatol. 2018; 78(2s1):s1-s23.e1. 2. zaenglein al, pathy al, schlosser bj, et al. guidelines of care for the management of acne vulgaris. j am acad dermatol. 2016.; 74(5):945-973.e33. 3. macdonald h, kelly rg, allen es, noble jf, kanegis la. pharmacokinetic studies on minocycline in man. clin pharmacol ther. 1973 sep-oct;14(5):852-61. development of a suitable receptor solution and extraction diluent for ex vivo drug permeation and penetration experiments in human skin • three receptor solutions were assessed for their ability to minimize degradation of minocycline during ex vivo permeation and penetration • 165 mm sodium acetate ph 5.0 with 0.01% brij-o20 • 50 mm mgcl2 in 115 mm sodium acetate ph 5.0 with 0.01% brij-o20 • 35 mm edta in 130 mm sodium acetate ph 5.0 with 0.01% brij-o20 • three different diluents were assessed for their suitability as extraction fluids for the recovery of minocycline from the surface of the skin, the skin layers (epidermis and dermis), and from a single drop of 2-octyl cyanoacrylate glue (surgiseal®) • 90/9/1 acetonitrile/water/formic acid • 90/9/1 methanol/water/formic acid • 25 mm mgcl2 in 90/9/1 methanol/water/formic acid) • method development tests determined 35 mm edta in 130 mm sodium acetate ph 5.0 with 0.01% brij-o20 was suitable as the receptor solution and that 90/9/1 methanol/ water/formic acid should be used as the extraction solvent skin penetration and permeation • foam samples were collapsed in a glass container an approximately 10 mg of the collapsed foam was dosed onto the skin (n=10) • flow was set at 10 µl/min and the formulation was allowed to penetrate through the skin for 12 hours • subsequently, two treatment paradigms were implemented: 1. sebaceous appendage intact: five skin samples were cleaned�and�heated�at�60°c�(140°f)�for�2�minutes�in�order� to manually separate the dermis from the epidermis 2. sebaceous appendage separation: the other five skin samples were cleaned and then treated with surgiseal® to extract sebaceous appendages. minocycline was analyzed for sebaceous appendage, dermis, and remaining epidermis figure 1: schematic representation of flow-through diffusion cell references presented at the 15th annual coastal dermatology symposium seattle, wa | october 3-6, 2019 introduction objective methods lack of ecg effects of bms-986165, an oral, selective tyrosine kinase 2 (tyk2) inhibitor: results from a thorough qt study in healthy subjects fall clinical dermatology conference • october 17–20, 2019 • las vegas, nv, usa ig girgis,1 a chimalakonda,1 jp jones iii,2 r dockens,1 d marchisin,1 r darbenzio,1 s singhal,1 j throup,1 s banerjee1 1bristol-myers squibb, princeton, nj, usa; 2pra health sciences, blue bell, pa, usa • tyk2, an intracellular signaling enzyme, activates signal transducer and activator of transcription (stat)–dependent gene expression and the functional responses of interleukin (il)-12, il-23, and type i interferons, which are involved in the pathogenesis of psoriasis and other immune-mediated disorders.1–6 • bms-986165 is an oral, selective inhibitor of tyk2. • in a 12-week, placebo-controlled, phase 2 trial in patients with moderate to severe plaque psoriasis, bms-986165 demonstrated an acceptable safety profile, and 67–75% of patients achieved psoriasis area and severity index 75 at week 12 (primary endpoint) at doses 3 mg twice daily versus 7% with placebo (p0.001).7 • in patients treated with the highest dose (12 mg once daily), the predicted mean maximum concentration (cmax) at steady state was 93.9 ng/ml, and no cardiovascular (including electrocardiogram [ecg]) abnormalities were reported.7 introduction • to determine the effect of bms-986165 plasma concentrations on the qt interval corrected for heart rate (hr) using fridericia’s method (qtcf), and on other 12-lead ecg-derived endpoints, in healthy subjects. objective study design • this study used a randomized, double-blind, positiveand placebo-controlled, 4-period crossover design (figure 1). • eligible subjects were randomized according to a 4-sequence williams design to receive 1 sequence of 4 treatments (all oral single doses): ○ placebo bms-986165 ○ 12 mg bms-986165 (a potential therapeutic dose) ○ 36 mg bms-986165 (supratherapeutic dose) ○ 400 mg moxifloxacin (positive control). • subjects fasted for approximately 10 hours prior to and 4 hours after study drug was administered on day 1 of each of the 4 treatment periods (days 1, 6, 11, and 16); there was a 5-day washout between each period. study population • key inclusion criteria: ○ healthy male and female subjects ○ age 18–50 years at screening ○ body mass index 18.0–32.0 kg/m2 and body weight 50 kg at screening ○ normal renal function (estimated glomerular filtration rate 80 ml/min/1.73 m2) at screening. • key exclusion criteria: ○ a personal history of clinically relevant cardiac disease ○ history of hypokalemia, personal history or family history of prolonged qt interval, or family history of sudden cardiac death at a young age ○ use of concomitant medications that prolong the qt/qtc interval within 4 weeks (or 5 half-lives) prior to study drug administration ○ secondor third-degree heart block at screening or baseline (day -1) ○ any history or risk of tuberculosis ○ a known or suspected autoimmune disorder. study assessments • on day 1 of each treatment period, following a 10-minute supine or semi-recumbent rest period, serial 12-lead ecg measurements were extracted from 24-hour continuous recordings using holter monitors in up to 10 replicates at 3 time points prior to dosing and at time points paired with pharmacokinetic sampling up to 24 hours post-dose. • physical examination, vital sign measurements, clinical laboratory evaluations, and safety ecgs were performed at selected times throughout the dosing interval. • safety was assessed by adverse event (ae) reporting throughout the study. study endpoints • the primary endpoint was placebo-adjusted change from baseline (i.e. pre-dose on day 1 per treatment period) in qtcf (qtcf). methods study population • a total of 40 subjects were screened and randomized and 38 subjects completed the study; 2 subjects were discontinued (1 due to an ae and 1 for other reasons). • demographic and other baseline characteristics are summarized in table 1. • baseline mean ecg parameters were within ranges for a healthy population (hr 61.7–63.5 beats per minute [bpm], qtcf 399.3–400.4 msec, pr 147.5–149.6 msec, qrs 104.0–104.6 msec). change from baseline in qtcf • the pattern of mean qtcf observed for bms-986165 closely followed that of placebo and did not suggest an effect on cardiac repolarization (figure 2). • the largest mean qtcf with bms-986165 at 2 hours post-dose was 0.8 msec (90% ci: -0.86 to 2.49) for the 12-mg dose and 3.0 msec (90% ci: 1.32 to 4.68) for the 36-mg dose. • the relationship between bms-986165 plasma concentration and qtcf was adequately described by a linear mixed-effects model (figure 3). ○ concentration–qtcf analysis predicted the exclusion of qtcf 10 msec for bms-986165 plasma concentrations of at least 500 ng/ml, which is 5× higher than cmax at the highest dose studied in phase 2 (12 mg once daily). • assay sensitivity was demonstrated by the effects of moxifloxacin. ○ a clear increase in mean qtcf was observed (peak at 2 hours post-dose: 12.9 msec [90% ci: 11.24 to 14.56]) (figure 2). ○ the lower bound of the 2-sided 90% ci of the predicted effect at the observed geometric mean cmax was 5 msec and the slope of the concentration–qtcf relationship was statistically significant (figure 4). results references 1. watford wt et al. immunol rev. 2004;202:139-156. 2. tokarski js et al. j biol chem. 2015;290:11061-11074. 3. volpe e et al. nat immunol. 2008;9:650-657. 4. geremia a et al. j exp med. 2011;208:1127-1133. 5. tucci m et al. clin exp immunol. 2008;154:247-254. 6. lazear hm et al. immunity. 2015;21:15-28. 7. papp k et al. n engl j med. 2018;379:1313-1321. acknowledgments this study was sponsored by bristol-myers squibb. professional medical writing and editorial assistance was provided by catriona mckay, phd, at caudex and was funded by bristol-myers squibb. disclosures igg, ac, rdo, dm, rda, ss, jt, sb: employees, shareholders: bristol-myers squibb. jpj iii: employee: pra health sciences, which has a contract with bristol-myers squibb on clinical development of bms-986165. previously presented at the european academy of dermatology and venerology (eadv), held october 9–13, 2019. change from baseline in hr • bms-986165 at doses of 12 mg and 36 mg had no clinically relevant effect on hr or ecg parameters. ○ the greatest mean hr of 4.0 bpm (90% ci: 2.57 to 5.53) was observed 1 hour post-dose with the highest dose of bms-986165 (36 mg; figure 5). ○ bms-986165 had no effect on pr and qrs intervals (data not shown). overall safety • most aes were mild in intensity and all treatment-emergent aes had resolved by the end of study (data not shown). • the most common ae related to bms-986165 treatment was headache. • key secondary endpoints: ○ qtcf for moxifloxacin (positive control) ○ change from baseline and placebo-corrected change from baseline for hr, qrs, and pr intervals (hr, qrs, and pr). statistical analysis • a total of 40 subjects (10 per treatment sequence) were screened and randomized to ensure 32 subjects with data from all treatment periods. ○ a sample size of 32 provided 95% power to exclude that bms-986165 caused more than a 10-msec qtc effect at clinically relevant plasma levels, as shown by the upper bound of the 2-sided 90% confidence interval (ci) of qtcf at the observed geometric mean cmax of bms-986165. ○ to demonstrate assay sensitivity with exposure–response analysis, it had to be shown that the qtcf of a single dose of 400 mg moxifloxacin exceeded 5 msec. • the primary analysis was based on exposure–response modeling of the relationship between bms-986165 and its metabolites and qtcf with the intent to exclude an effect 10 msec at clinically relevant plasma concentrations. • assay sensitivity was evaluated by an exposure–response analysis of the effect on qtcf of moxifloxacin using a similar model. • secondary analyses of the effect of bms-986165 on qtcf, hr, qrs, and pr were evaluated at each post-dose time point using the intersection union test. • this study demonstrated that the oral, selective tyk2 inhibitor bms-986165, at single doses of 12 mg (therapeutic) and 36 mg (supratherapeutic), did not have a clinically relevant effect on ecg parameters, including qtcf and hr, in healthy subjects. • based on this analysis, a clinically meaningful qtcf prolongation 10 msec can be excluded for bms-986165 plasma concentrations of at least 500 ng/ml. conclusions 15 10 5 0 -5 � � q tc f (m se c) time post-dose (hours) 2412106432.521.510.5 bms-986165 12 mg bms-986165 36 mg moxifloxacin figure 2: placebo-corrected qtcf over time (qt/qtc set; n=40). least squares mean and 90% cis were based on a linear mixed-effects model: qtcf = period + sequence + time + treatment + time*treatment + baseline qtcf. an unstructured covariance structure was used to specify the repeated measures (time for subjects within period). baseline was defined as the mean of the 4 pre-dose values on days 1, 6, 11, and 16 in each corresponding treatment period. the black dotted line indicates the threshold of 10 msec. qt/qtc analysis set: all subjects in the safety set with measurements at baseline and on-treatment with at least 1 post-dose time point with a valid qtcf; all 40 subjects met the criteria to be included in the qt/qtc analysis set. qtcf=change in qtcf; qtcf=change from baseline in qtcf; ci=confidence interval. 10 5 0 -5 � � q tc f (m se c) 0 100 200 300 400 500 bms-986165 concentration (ng/ml) figure 3: model-predicted and observed mean (90% ci) placebo-corrected qtcf across deciles of plasma concentrations for bms-986165 (pk/qtc set; n=40). prediction was based on the model qtcf = 0.19 + [concentrations of bms-986165*0.0059]. the pink-filled circles with vertical bars denote the observed mean qtcf with 90% ci displayed at the median plasma concentration within each decile for bms-986165. the solid black line with grey shaded area denotes the model-predicted qtcf with 90% ci. the horizontal pink line with notches shows the range of concentrations divided into deciles for bms-986165. the black dotted line indicates the threshold of 10 msec. the distance between each decile represents the point at which 10% of the data are present; the first notch to second notch denotes the first 10% of the data; the second notch to third notch denotes 10–20% of the data; and so on. pk/qtc analysis set: all subjects in both the pk and qt/qtc sets with at least 1 pair of post-dose pk and qtcf data from the same time point (pk set: all randomized subjects who took at least 1 dose of bms-986165 or moxifloxacin and had at least 1 evaluable pk concentration); all 40 subjects met the criteria to be included in the pk and pk/qtc analysis sets. qtcf=change from baseline in qtcf; ci=confidence interval; pk=pharmacokinetic. 20 15 10 5 0 � � q tc f (m se c) 0 500 1000 1500 2000 2500 moxifloxacin concentration (ng/ml) 3000 moxifloxacin figure 4: predicted placebo-corrected qtcf interval at geometric mean peak moxifloxacin concentrations (pk/qtc set; n=40). prediction was based on the model δδqtcf = 3.98 + concentrations of moxifloxacin*0.0045. the solid black line with grey shaded area denotes the model-predicted mean (90% ci) qtcf. the purple diamond with shaded bands denotes the estimated mean (90% ci) qtcf at the geometric mean (90% ci) cmax of moxifloxacin. the black dotted line indicates the threshold of 10 msec. pk/qtc analysis set: all subjects in both the pk and qt/qtc sets with at least 1 pair of post-dose pk and qtcf data from the same time point (pk set: all randomized subjects who took at least 1 dose of bms-986165 or moxifloxacin and had at least 1 evaluable pk concentration); all 40 subjects met the criteria to be included in the pk and pk/qtc analysis sets. qtcf=change from baseline in qtcf; ci=confidence interval; cmax=maximum concentration; pk=pharmacokinetic. 5 0 -5 � � h r (b pm ) time post-dose (hours) 2412106432.521.510.5 bms-986165 12 mg bms-986165 36 mg moxifloxacin figure 5: placebo-corrected hr over time (qt/qtc set; n=40). least squares mean and 90% ci based on a linear mixed-effects model: δhr = period + sequence + time + treatment + time*treatment + baseline hr. an unstructured covariance structure was used to specify the repeated measures (time for subjects within period). baseline was defined as the mean of the 4 pre-dose values on days 1, 6, 11, and 16 in each corresponding treatment period. the black dotted line indicates the reference line of 0 bpm. qt/qtc analysis set: all subjects in the safety set with measurements at baseline and on-treatment with at least 1 post-dose time point with a valid qtcf; all 40 subjects met the criteria to be included in the qt/qtc analysis set. hr=change in heart rate; hr=change from baseline in heart rate; qtcf=change from baseline in qtcf; bpm=beats per minute; ci=confidence interval; hr=heart rate. screening (days -28 to -1) period 1 (days 1–5) period 2 (days 6–10) period 3 (days 11–15) period 4 (days 16–20) discharge (day 21) follow-up phone call (day 26 ± 2) first study treatment second study treatment third study treatment fourth study treatment figure 1: study design. subjects were randomly assigned to 1 of 4 treatment sequences that included placebo, bms-986165 12 mg, bms-986165 36 mg, and moxifloxacin according to the williams design; 10 subjects were assigned to each treatment sequence. table 1: summary of demographics and baseline characteristics. safety set (n=40) sex, n (%) male 28 (70.0) female 12 (30.0) race, n (%) white 12 (30.0) black or african american 27 (67.5) asian 1 (2.5) age (years), mean (sd) 33.3 (8.9) bmi (kg/m2), mean (sd) 26.5 (3.1) the safety set included all randomized subjects who took at least 1 dose of a study treatment; all 40 subjects met the criteria to be included in the safety analysis set. bmi=body mass index. scientific content on-demand copies of this poster obtained through quick response (qr) code are for personal use only and may not be reproduced without permission from fall clinical dermatology conference and the authors of this poster. links are valid for 30 days after the congress presentation date. to receive a copy of this poster scan qr code via a barcode reader application powerpoint presentation the i31-gene expression profile test for cutaneous melanoma identifies patients with head and neck tumors who could forego sentinel lymph node biopsy background ›up to 25% of patients with cutaneous melanoma (cm) have tumors on the head or neck (hn).1 these patients have a worse prognosis than those with tumors at other locations.2 ›hn tumors present additional complexities for sentinel lymph node biopsy (slnb) due to complex lymphatic drainage systems, technical challenges related to the location, and complex surgical techniques required around cranial nerves and vasculature.3 ›an algorithm integrating the 31-gene expression profile (31-gep) molecular risk stratification test with clinical and pathological features (i31-gep) provides a precise risk prediction for slnb positivity, which can help patients and clinicians make riskaligned decisions about undergoing slnb among a high-risk population.4 separately, the i31-gep has been validated to predict risk-of-recurrence. acknowledgments & disclosures references ›ts and mt have no conflicts of interest. bm is an employee and shareholder/option holder of castle biosciences, inc. presented at the winter clinical 2023 conference. teo soleymani, md1, brian martin, phd2, michael tassavor, md3 1mohs micrographic and dermatologic surgery, cutaneous oncology, division of dermatology, david geffen school of medicine, university of california, los angeles, ca, 2castle biosciences, inc. friendswood, tx, 3skin cancer center, cincinnati, oh ›without sacrificing sensitivity, the i31-gep for slnb could reduce the number of unnecessary slnbs by 37% overall and 63% for t1a tumors and 50% for t1b tumors, specifically. ›no patients with an i31-gep predicted sln positivity risk of <5% had a positive slnb. ›the i31-gep for slnb can help guide riskaligned patient care decisions in patients considering slnb. conclusions ›patients from a previously published multicenter cohort study4 with preslnb stage i tumors (t1-t2a) located in the hn region and who had undergone slnb were included in the analysis (n=159). patients with <5% and ≥5% risk predicted by the i31-gep were considered low or high-risk, respectively. a low-risk prediction was considered a negative test result, and a high-risk prediction was considered a positive test result for i31-gep accuracy calculations. methods 1. zito pm, et al: melanoma of the head and neck [internet], in statpearls. treasure island (fl), 2020. 2. shashanka r, et al: head and neck melanoma. isrn surg 2012:948302, 2012. 3. giudice g, et al: sentinel lymph node biopsy in head and neck melanoma. g chir 35:149–55, 2014. 4. whitman ed, et al: integrating 31-gene expression profiling with clinicopathologic features to optimize cutaneous melanoma sentinel lymph node metastasis prediction. jco precision oncology 1466–1479, 2021 figure 2. the i31-gep for slnb can reduce slnb rate while increasing the positivity rate i31-gep for slnb percent sensitivity 100% specificity 39.1% negative predictive value 100% results table 1. the i31-gep for slnb has high sensitivity to identify patients likely to have sln metastasis scan or click here for more info figure 1. slnb reduction rates in each t-category when using the i31-gep for slnb to guide decisions no patient (0/59) with an i31-gep predicted sln positivity risk of <5% had a positive slnb. using the i31-gep for slnb to guide slnb decisions for t1-t2a tumors on the h&n achieved a 37% (59/159) slnb reduction rate and increased the positivity rate from 5% (8/159 using ajcc staging) to 8% (8/100 using i31-gep risk prediction). sensitivity: true positive/(true positive + false negative); specificity: true negative/(true negative + false positive); negative predictive value: true negative/(true negative + false negative) h&n tumor, received slnb (t1a hr-t2a) perform slnb sln – 95.0% (151/159) sln+ 5% (8/159) i31-gep for slnb low risk of sln+ (<5%) high risk of sln+ (>10%) perform slnb sln+ 8% (8/100) could have avoided slnb sln100% (59/59) ajcc staging ›using the i31-gep to identify patients for slnb can: ›personalize melanoma clinical management plans ›reduce the number of unnecessary slnbs ›reduce slnb-associated complications ›reduce healthcare costs clinical impact https://castlebiosciences.com/research-development/publications/ slide 1 background • crisaborole ointment is a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of mild to moderate ad 1 • the safety and efficacy of crisaborole was previously established in 2 identically designed, multicenter, randomized, double-blind, vehiclecontrolled phase 3 trials (ad-301: nct02118766; ad-302: nct02118792)2 • within these trials, pruritus severity was measured using the severity of pruritus scale (sps), a 4-point rating scale ranging from (none: no itching) to 3 (severe: bothersome itching/scratching which disturbs sleep) adapted from the atopic dermatitis severity index3 to quantify itch over a 24-hour recall period (table 1) • in the prespecified analysis, sps data were analyzed using each sps observation as a single measurement2 • subsequent validation analysis has determined that the mean of at least 2 sps observations is necessary to provide a reliable measure of pruritus severity table 1. severity of pruritus scale (sps) instructions: please think about your itching (or your child’s itching if you are completing for your child) over the past 24 hours and choose the category that best describes it. score grade definition 0 none no itching 1 mild occasional, slight itching/scratching 2 moderate constant or intermittent itching/scratching which is not disturbing sleep 3 severe bothersome itching/scratching which is disturbing sleep objectives • to conduct an extended analysis of the sps data from the pivotal phase 3 trials to assess the efficacy of crisaborole for treatment of adassociated pruritus using the mean of at least 2 sps observations to provide a reliable measure of pruritus methods data source • data were sourced from 2 identically designed, multicenter, vehicle-controlled, double-blind, phase 3 crisaborole trials (ad-301: nct02118766; ad-302: nct02118792)2 – eligible patients were ≥2 years of age, with a clinical diagnosis of ad with ≥5% treatable body surface area involvement and a baseline investigator’s static global assessment (isga) score of mild (2) or moderate (3) (the isga is a 5-point rating scale measuring overall disease severity from clear [0] to severe [4]) – patients were randomly assigned 2:1 to receive crisaborole or vehicle and instructed to apply the study drug to each lesion twice daily for 28 days – pruritus severity was recorded twice daily using the sps via electronic diary from baseline/day 1 through day 29 analysis • improvement in pruritus was indicated by an sps score ≤1, with at least a 1-grade improvement from baseline • a minimum of 2 sps observations were averaged for each analysis to meet the test-retest reliability threshold of acceptability (intraclass correlation coefficient ≥0.70) – baseline for all analyses was the mean of ≥2 sps measurements on day 1 time to improvement in pruritus • based on daily sps values, calculated as the mean of ≥2 sps measurements on that day proportion of patients who experienced improvement in pruritus • assessed at each weekly study visit and calculated using the mean of all available postbaseline sps scores for the patient during the corresponding preceding week (generally up to 14 measurements) pruritus score by week • weekly sps scores were calculated as the mean of all available postbaseline sps scores for the patient during the corresponding preceding week (up to 14 measurements) • scores were analyzed using a repeated-measures longitudinal model with fixed effects for treatment, visit, treatment-by-visit interaction, and baseline value • the previously estimated clinically important difference (cid) of 0.20 was used as a threshold to assess the clinical meaningfulness of the treatment effect proportion of responders by week • per the pruritus score by week analysis, weekly sps scores were calculated as the mean of all available postbaseline sps scores for the patient during the preceding corresponding week (up to 14 measurements) • responders were defined by a previously estimated clinically important response (cir) of ≥0.19-point reduction in severity of pruritus from baseline the effect of crisaborole ointment, 2%, on pruritus in patients with atopic dermatitis (ad): an extended analysis gil yosipovitch,1 eric simpson,2 huaming tan,3 robert a. gerber,3 thomas luger,4 sonja ständer,4 wynnis tom,5 joseph c. cappelleri,3 andrew g. bushmakin,3 william c. ports,3 anna m. tallman6 1university of miami, miller school of medicine, miami, fl, usa; 2oregon health and science university, portland, or, usa; 3pfizer inc., groton, ct, usa; 4university hospital münster, münster, germany; 5rady children’s hospital-san diego, san diego, ca, usa; 6icon plc, gaithersburg, md, usa; 6pfizer inc., new york, ny, usa presented at the 2017 fall clinical dermatology conference; october 12-15, 2017; las vegas, nv results • the intent-to-treat population included 759 patients in ad-301 (503 crisaborole; 256 vehicle) and 763 patients in ad-302 (513 crisaborole; 250 vehicle)2 • the mean baseline sps scores (standard deviation [sd]) were 1.83 (0.79) for crisaborole-treated patients and 1.75 (0.83) for vehicle-treated patients in ad-301 and were 1.81 (0.77) for crisaborole-treated patients and 1.79 (0.72) for vehicle-treated patients in ad-302 time to improvement in pruritus • median time to improvement in pruritus was significantly less for crisaborole-treated patients than for vehicle-treated patients in both trials (figure 1) – ad-301: 5.0 days (95% ci, 4.0-6.0 days) for crisaborole-treated patients compared with 10.0 days (95% ci, 7.0-18.0 days) for vehicle-treated patients (p = 0.0003) (figure 1a) – ad-302: 6.0 days (95% ci, 5.0-7.0 days) for crisaborole-treated patients compared with 9.0 days (95% ci, 7.0-13.0 days) for vehicle-treated patients (p = 0.0087) (figure 1b) figure 1. kaplan-meier plot of time to improvement in pruritus. (a) ad-301 and (b) ad-302. 0 20 40 60 80 100 s u b je c ts w h o e x p e ri e n c e d im p ro v e m e n t in p ru ri tu s , % 10 30 50 70 90 10 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 122 23 24 25 26 27 28 29 30 31 32 days after dosing 0 20 40 60 80 100 s u b je c ts w h o e x p e ri e n c e d im p ro v e m e n t in p ru ri tu s , % 10 30 50 70 90 10 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 122 23 24 25 26 27 28 29 30 31 32 days after dosing crisaborole, 2% n = 381 5.0 4.0-6.0 0.0003 median, days 95% ci p value for log-rank test vehicle n = 190 10.0 7.0-18.0 — crisaborole, 2% n = 383 6.0 5.0-7.0 0.0087 median, days 95% ci p value for log-rank test vehicle n = 181 9.0 7.0-13.0 — a b crisaborole vehicle crisaborole vehicle bid, twice daily; sps, severity of pruritus scale. improvement in pruritus was indicated by an sps score ≤1, with at least a 1-grade improvement from baseline. baseline was the mean of at least 2 sps assessments on day 1. patients with fewer than 2 sps assessments on day 1 were considered to have missing data. sps daily values were calculated as the mean of 2 or more assessments on that day. if fewer than 2 assessments were available, sps was considered missing. analysed using kaplan-meier methods and the log-rank test. proportion of patients who experienced improvement in pruritus • a significantly greater proportion of crisaborole-treated patients exhibited improvement in pruritus at each weekly time point than vehicle-treated patients in both trials (figure 2) – ad-301 week 4: 37% (95% ci, 32%-42%) of crisaborole-treated patients compared with 21% (95% ci, 15%-27%) of vehicle-treated patients (p < 0.0001) (figure 2a) – ad-302 week 4: 34% (95% ci, 30%-39%) of crisaborole-treated patients compared with 21% (95% ci, 14%-27%) of vehicle-treated patients (p = 0.0006) (figure 2b) figure 2. proportion of patients who experienced improvement in pruritus. (a) ad-301 and (b) ad-302. 21% 32% 35% 37% 10% 17% 19% 21% 0 10 20 30 40 50 a week 1 week 2 week 3 week 4 p ro p o rt io n o f p a ti e n ts e x p e ri e n c in g i m p ro v e m e n t in p ru ri tu s , % (s c o re o f 0 o r 1 w it h ≥ 1 -g ra d e re d u c ti o n f ro m b a s e li n e ) p ro p o rt io n o f p a ti e n ts e x p e ri e n c in g i m p ro v e m e n t in p ru ri tu s , % (s c o re o f 0 o r 1 w it h ≥ 1 -g ra d e re d u c ti o n f ro m b a s e li n e ) crisaborole vehicle p < 0.0001 p = 0.0003 p < 0.0001 p < 0.0001 number of patients crisaborole vehicle 80 19 122 30 129 33 135 36 16% 27% 19% 34% 9% 14% 16% 21% 0 10 20 30 40 50 b week 1 week 2 week 3 week 4 crisaborole vehicle p < 0.0002 p = 0.0120 p < 0.0004 p < 0.0006 number of patients crisaborole vehicle 61 16 103 25 106 27 125 34 sps, severity of pruritus scale. improvement in pruritus was indicated by an sps score ≤1, with at least a 1-grade improvement from baseline. baseline was the mean of at least 2 sps assessments on day 1. patients with fewer than 2 sps assessments on day 1 were considered to have missing data. weekly sps scores for each subject were calculated as the mean of all available postbaseline sps scores for the subject during the corresponding week (generally up to 14 measurements). only subjects with a mean baseline value and a postbaseline assessment were included. error bars denote standard error. pruritus score by week • crisaborole-treated patients exhibited significantly lower mean pruritus scores than vehicle-treated patients at each weekly time point in both trials (figure 3) • the least-squares mean difference between pruritus scores for crisaborole-treated and vehicle-treated patients was ≥0.20 at all time points in both trials, which exceeded the cid previously identified (figure 3) figure 3. least-squares mean difference in pruritus score. (a) ad-301 and (b) ad-302. crisaborole vehicle difference from vehicle n ls mean se n ls mean se difference, 95% ci p value week 1 381 1.19 0.03 180 1.32 0.04 –0.20 (–0.11, –0.30) <0.0001 week 2 376 1.09 0.03 175 1.31 0.05 –0.22 (–0.11, –0.33) <0.0001 week 3 368 1.09 0.03 170 1.37 0.05 –0.28 (–0.16, –0.40) <0.0001 week 4 363 1.08 0.04 165 1.35 0.05 –0.26 (–0.13, –0.38) <0.0001 ls mean difference, 95% ci favors crisaborole –0.50 –0.25 0.00 crisaborole vehicle difference from vehicle n ls mean se n ls mean se difference, 95% ci p value week 1 381 1.16 0.03 188 1.42 0.04 –0.26 (–0.16, –0.36) <0.0001 week 2 377 1.03 0.03 181 1.36 0.05 –0.33 (–0.22, –0.45) <0.0001 week 3 373 1.01 0.04 175 1.32 0.05 –0.31 (–0.19, –0.44) <0.0001 week 4 363 0.97 0.04 170 1.28 0.05 –0.31 (–0.18, –0.44) <0.0001 ls mean difference, 95% ci cid favors crisaborole –0.50 –0.25 0.00 1 2 3 4 a b cid cid, clinically important difference; ls, least squares; se, standard error; sps, severity of pruritus scale. the dotted line represents the estimated cid of 0.20. baseline was the mean of at least 2 sps assessments on day 1. subjects with fewer than 2 sps assessments on day 1 were considered to have missing data. weekly sps scores for each subject were calculated as the mean of all available postbaseline sps scores for the subject during the corresponding week (generally up to 14 measurements). only subjects with nonmissing baseline scores were included. all statistics were derived from a repeated-measures model with fixed effects for treatment, visit, treatment-by-visit interaction, and baseline value. error bars denote standard error of least-squares mean. proportion of responders by week • a significantly greater proportion of crisaborole-treated patients experienced cir (defined as ≥0.19-point reduction in severity of pruritus from baseline) than vehicle-treated patients at each time point in ad-301 and at weeks 2 and 3 in ad-302 (figure 4) figure 4. proportion of patients experiencing clinically important response. (a) ad-301 and (b) ad-302. 72% 75% 74% 75% 53% 56% 57% 57% 0 20 40 60 80 100 week 1 week 2 week 3 week 4 p ro p o rt io n o f p a ti e n ts c la s s if ie d a s r e s p o n d e rs , % (d e fi n e d a s ≥ 0 .1 9 -p o in t re d u c ti o n i n s e v e ri ty fr o m b a s e li n e ) p < 0.0001 p < 0.0001 p < 0.0001 p < 0.0001 number of patients crisaborole vehicle 276 99 284 101 276 99 271 97 73% 76% 74% 72% 66% 64% 63% 64% 0 20 40 60 80 100 week 1 week 2 week 3 week 4 p ro p o rt io n o f p a ti e n ts a c h ie v in g i m p ro v e m e n t in p ru ri tu s , % (s c o re o f 0 o r 1 w it h ≥ 1 -g ra d e re d u c ti o n f ro m b a s e li n e ) p = 0.0045 p = 0.0898 p = 0.0117 p = 0.0828 number of patients crisaborole vehicle 227 118 286 112 272 107 261 106 a crisaborole vehicle b crisaborole vehicle sps, severity of pruritus scale. responders were defined by a ≥0.19-point reduction in severity of pruritus from baseline. baseline was the mean of at least 2 sps assessments on day 1. weekly sps scores for each subject were calculated as the mean of all available postbaseline sps scores for the subject during the corresponding week (generally up to 14 measurements). only subjects with an average baseline and postbaseline assessments were included. conclusions • the results of this extended analysis confirm that crisaborole is effective in treating ad-associated pruritus – patients treated with crisaborole experienced improvement in pruritus earlier than vehicle-treated patients – crisaborole-treated patients exhibited significantly lower pruritus scores than vehicle-treated patients, with a difference that was considered clinically meaningful – a greater proportion of crisaborole-treated patients experienced improvement in severity of pruritus and cir than vehicle-treated patients references 1. eucrisa (crisaborole) ointment, 2%, for topical use [prescribing information]. palo alto, ca: anacor pharmaceuticals, inc.; 2016. 2. paller as et al. j amer acad of derm. 2016;75(3):494-503.e6. 3. van leent ej et al. arch dermatol. 1998;134(7):805-809. acknowledgments editorial/medical writing support under the guidance of the authors was provided by jemimah walker, phd, and corey mandel, phd, at apothecom, san francisco, ca, usa, and was funded by pfizer inc., new york, ny, usa, in accordance with good publication practice (gpp3) guidelines (ann intern med. 2015;163:461-464). fc17posterpfizeryosipovitcheffectcrisaborole.pdf one line title two line title 1. burke jr, et al. sci transl med. 2019;11:eaaw1736. 2. sotyktu™ (deucravacitinib) [package insert]. princeton, nj: bristol-myers squibb company; september 2022. 3. armstrong aw, et al. j am acad dermatol. 2022;s0190-9622(22)02256-3. doi: 10.1016/j.jaad.2022.07.002. online ahead of print. 4. strober b, et al. j am acad dermatol. 2022;s0190-9622(22)02643-3. doi: 10.1016/j.jaad.2022.08.061. online ahead of print. 5. warren rb, et al. presented at the european academy of dermatology and venereology 30th congress; september 29—october 2, 2021. 6. warren rb, et al. presented at the european academy of dermatology and venereology spring symposium; may 12–14, 2022. 7. wrobleski st, et al. j med chem. 2019;62:8973-8995. 8. walsh ja, et al. j am acad dermatol. 2013;69:931-937. 9. merola jf, et al. j invest dermatol. 2018;138:1955-1961. deucravacitinib 6 mg qdplacebo (n = 166) deucravacitinib 6 mg qd apremilast 30 mg bid≥pasi 50 1 :2 :1 r an d om iz at io n 52weeks deucravacitinib 6 mg qd (n = 332) 16 24 <pasi 50 apremilast 30 mg bida (n = 168) primary endpoint 0 ≥pasi 75 placebo (n = 255) deucravacitinib 6 mg qd (n = 511) deucravacitinib 6 mg qd deucravacitinib 6 mg qd<pasi 75 deucravacitinib 6 mg qd deucravacitinib 6 mg qd apremilast 30 mg bida (n = 254) ≥pasi 75 52weeks 1:1 placebob deucravacitinib 6 mg qd 16 24 <pasi 75 primary endpoint 1 :2 :1 r an d om iz at io n placebob deucravacitinib 6 mg qd 0 ≥pasi 75 -90 -80 -70 -60 -50 -40 -30 -20 -10 0 0 1 2 4 8 12 16 20 24 m ea n pe rc en ta ge c fb ‡ ‡§ ‡§ ‡§ § § -11.3% -43.2% -60.0% bsa over 24 weeks weeks -66.6% -46.1% ‡ 0 10 20 30 40 50 60 70 80 90 0 1 2 4 8 12 16 20 24 m ea n re sp on se r at e, % o f pa ti en ts weeks -90 -80 -70 -60 -50 -40 -30 -20 -10 0 0 1 2 4 8 12 16 20 24 28 32 36 40 44 48 52 m ea n pe rc en ta ge c fb -62.9% • tyrosine kinase 2 (tyk2) is an intracellular enzyme that mediates cytokine signaling (eg, interleukin-23, type 1 interferons) involved in psoriasis pathogenesis1 • deucravacitinib, an oral, selective, allosteric tyk2 inhibitor, is approved by the us food and drug administration for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy2 – uniquely binds to the tyk2 regulatory domain with high selectivity and inhibits tyk2 via an allosteric mechanism1 (figure 1) • the phase 3 poetyk pso-1 and pso-2 trials demonstrated that deucravacitinib was superior to placebo and apremilast in patients with moderate to severe plaque psoriasis based on the coprimary endpoints of a ≥75% reduction from baseline in psoriasis area and severity index (pasi 75) and a static physician’s global assessment score of 0 (clear) or 1 (almost clear) with a ≥2-point improvement from baseline (spga 0/1) at week 163,4 • clinical responses were maintained through 52 weeks in patients who received continuous deucravacitinib treatment and were improved in patients who switched from placebo to deucravacitinib at week 165 • the 2-year efficacy and safety of deucravacitinib in the poetyk long-term extension trial was consistent with weeks 0–52 of the poetyk pso-1 and pso-2 trials6 -90 -80 -70 -60 -50 -40 -30 -20 -10 0 0 1 2 4 8 12 16 20 24 m ea n pe rc en ta ge c fb -72.6% ‡§ ‡§ § § -55.1% ‡ *‡ ‡§ -19.9% -55.9% -76.1% † deucravacitinib, an oral, selective tyrosine kinase 2 inhibitor, versus placebo and apremilast in moderate to severe plaque psoriasis: analysis of body surface area involvement in the phase 3 poetyk pso-1 and pso-2 trials jo lambert,1 carle paul,2 alice b gottlieb,3 yves poulin,4 diamant thaçi,5 stephen tyring,6 chien-hui hong,7 lauren hippeli,8 renata m kisa,8 lluís puig9 1ghent university, ghent, belgium; 2toulouse university and chu, toulouse, france; 3icahn school of medicine at mount sinai, new york, ny, usa; 4université laval, hôpital hotel-dieu de québec, and centre de recherche dermatologique du québec métropolitain, québec, qc, canada; 5university of lübeck, lübeck, germany; 6university of texas health science center and center for clinical studies, houston, tx, usa; 7national yang ming chiao tung university school of medicine, taipei city, and kaohsiung veterans general hospital, kaohsiung, taiwan; 8bristol myers squibb, princeton, nj, usa; 9hospital de la santa creu i sant pau and universitat autònoma de barcelona, barcelona, spain presented at the 2022 fall clinical dermatology conference; october 20–23, 2022; las vegas, nv this is an encore of the 2022 spin poster email for jo lambert, md, phd: jo.lambert@uzgent.be this poster may not be reproduced without written permission from the authors. figure 1. mechanism of action of deucravacitinib atp, adenosine 5’-triphosphatase; jak, janus kinase; tyk2, tyrosine kinase 2. figure 3. mean percentage changes in bsa and bsa × spga scores over 24 weeks in poetyk pso-1 and pso-2 pooled results *p < 0.02 vs apremilast. †p = 0.0002 vs placebo. ‡p < 0.0001 vs placebo. §p < 0.0001 vs apremilast. mbocf was used to impute missing data; baseline observation was carried forward for patients who discontinued due to lack of efficacy or adverse events. bsa, body surface area; bsa × spga, body surface area × static physician’s global assessment score; cfb, change from baseline; mbocf, modified baseline observation carried forward. figure 5. mean change from baseline responses in bsa and bsa × spga during poetyk pso-1: weeks 0‒52 references acknowledgments • this study was sponsored by bristol myers squibb • writing and editorial assistance was provided by liz rockstein, phd, of peloton advantage, llc, an open health company, parsippany, nj, usa, funded by bristol myers squibb disclosures jl: unrestricted grants: abbvie, almirall, celgene, eli lilly, janssen-cilag, leo pharma, novartis, and ucb; speaker: abbvie, almirall, bristol myers squibb, janssen-cilag, pfizer, and ucb; consultant: abbvie, bristol myers squibb, celgene, eli lilly, janssen-cilag, leo pharma, novartis, and ucb. cp: grants and consultant: abbvie, almirall, amgen, boehringer ingelheim, bristol myers squibb, celgene, eli lilly, janssen, leo pharma, merck, mylan, novartis, pfizer, sandoz, and ucb. abg: honoraria or consultation fees: anaptsysbio, avotres, amgen, boehringer ingelheim, bristol myers squibb, dermavant, eli lilly, janssen, novartis, pfizer, sanofi, sun pharma, and xbiotech (stock options for an ra project); research grants (paid to institution): anapytsysbio, janssen, novartis, ortho, sun pharma, and ucb, and sun pharma. yp: honoraria or consultation fees: abbvie, amgen, biogen, boehringer ingelheim, celgene, eli lilly, leo pharma, merck-serono, merck sharp & dohme, novartis, pfizer, regeneron, roche, sandoz, sanofi, and ucb; research grants or participation in clinical trials (paid to institution): abbvie, amgen, boehringer ingelheim, celgene, eli lilly, janssen, leo pharma, novartis, pfizer, regeneron, roche, sanofi, and ucb. dt: grant/research support, consultant, scientific advisory board, and speakers bureau: abbvie, almirall, amgen, biogen idec, boehringer ingelheim, bristol myers squibb, eli lilly, galapagos, galderma, janssen-cilag, leo pharma, novartis, pfizer, regeneron, roche, sandoz-hexal, sanofi, target-solution, and ucb. st: participation in clinical trials: bristol myers squibb. c-hh: principal investigator: bristol myers squibb, g&e biotechnology, and teva; lecture fees: abbvie, bristol myers squibb, eli lilly, leo pharma, mylan, novartis, pfizer, roche-posay, and sanofi. lh and rmk: employees and shareholders: bristol myers squibb. lp: honoraria or consultation fees: abbvie, almirall, amgen, baxalta, biogen, boehringer ingelheim, celgene, eli lilly, fresenius kabi, gebro, janssen, leo pharma, merck-serono, merck sharp & dohme, mylan, novartis, pfizer, regeneron, roche, samsung bioepis, sandoz, sanofi, and ucb; research grants or participation in clinical trials (paid to institution): abbvie, almirall, amgen, boehringer ingelheim, celgene, eli lilly, janssen, leo pharma, novartis, pfizer, regeneron, roche, sanofi, and ucb; speakers bureau: celgene, eli lilly, janssen, merck sharp & dohme, novartis, and pfizer. synopsis • responses, including body surface area (bsa) involvement and the composite endpoint bsa × spga, were also monitored in both poetyk pso-1 and pso-2 to determine deucravacitinib efficacy in multiple endpoints – pasi is the standard efficacy outcome for clinical trials but is time consuming and less meaningful for clinicians in everyday practice8 – spga is also standard for clinical trials but focuses on plaque qualities and does not include an assessment of bsa involvement8,9 – together, bsa and bsa × spga can be useful proxies for pasi in clinical practice for assessment of disease severity in patients with moderate to severe plaque psoriasis9 objective • to evaluate the efficacy of deucravacitinib over 52 weeks based on bsa involvement and bsa × spga methods study designs • the study designs for poetyk pso-1 and pso-2 are illustrated in figure 2 • patients meeting the following criteria were eligible to enroll in one of the studies: – age ≥18 years – diagnosis of moderate to severe plaque psoriasis • baseline pasi ≥12, spga ≥3, and bsa involvement ≥10% • patient randomization in poetyk pso-1 and pso-2 was stratified by geographic region, body weight, and prior biologic use • bsa was estimated using the handprint method: the size of the patient’s handprint, including fingers and thumb, represented 1% of bsa involvement outcomes • the current analysis examined mean percentage change from baseline in bsa and bsa × spga • response rates for a ≥75% improvement from baseline in bsa × spga (bsa × spga 75) were also reported • efficacy outcomes for weeks 0‒24 were evaluated using the pooled poetyk pso-1/pso-2 population • maintenance of response through week 52 was examined in the poetyk pso-1 population only since it allowed assessment of continuous deucravacitinib treatment without any changes statistical methods • modified baseline observation carried forward (mbocf) was used for change from baseline endpoints – baseline observation was carried forward for patients who discontinued due to lack of efficacy or adverse events – for patients who discontinued the study treatment for other reasons or had a missing value, the last valid observation was carried forward (including the baseline value as applicable) • nonresponder imputation (nri) was used for bsa × spga 75 – patients who discontinued the study treatment or study or had missing endpoint data prior to time point of comparison were imputed as nonresponders • patients were excluded if data were missing solely due to covid-19 results • a total of 1686 patients were randomized across the poetyk pso-1 and pso-2 trials (table 1) • mean baseline bsa and bsa × spga scores were generally similar in each treatment group in poetyk pso-1 and pso-2 (table 1) conclusions • in the poetyk pso-1 and pso-2 trials, deucravacitinib treatment was associated with greater improvements in bsa, bsa × spga, and bsa × spga 75 over time compared with placebo and apremilast in patients with moderate to severe plaque psoriasis • deucravacitinib was associated with long-term improvements in response rates and maintenance of response in patients continuously treated over 52 weeks and in those who switched to deucravacitinib following 16 weeks of placebo deucravacitinib (allosteric inhibitor) unique tyk2 regulatory domain catalytic domain (highly conserved across jak family) atp-binding active site (other kinase inhibitors) tyk2 selectivity in cells1,7: • ≥100-fold greater selectivity for tyk2 vs jak 1/3 • ≥2000-fold greater selectivity for tyk2 vs jak 2 weeks 0‒52 (poetyk pso-1 population) • findings from poetyk pso-1 demonstrated maintenance of bsa and bsa × spga results in patients who received continuous deucravacitinib treatment, with mean percentage reductions of 74.6% and 81.4%, respectively, from baseline to week 52 (figure 5) • patients who switched from placebo to deucravacitinib at week 16 had similar mean percentage reductions at week 52 (bsa, 75.6%; bsa × spga, 84.4%) to patients treated continuously with deucravacitinib (figure 5) • bsa × spga 75 responses were maintained through week 52 in patients who received continuous deucravacitinib treatment and improved in patients who switched from placebo to deucravacitinib at week 16, with week 52 response rates that were similar between the groups (figure 6) *p < 0.0001 vs placebo. nonresponder imputation was used to impute missing data. bsa × spga 75, ≥75% improvement from baseline in body surface area × static physician’s global assessment score. deucravacitinib placebo apremilast patients, n 843deucravacitinib 422apremilast 421placebo 843 422 421 843 422 421 843 422 421 843 422 421 843 422 421 843 422 421 842 421 na 836 422 na bsa × spga over 24 weeks weeks figure 6. bsa × spga 75 response rates during poetyk pso-1: weeks 1‒52 0 10 20 30 40 50 60 70 80 90 0 1 2 4 8 12 16 20 24 28 32 36 40 44 48 52 m ea n re sp on se r at e weeks * * * * 332 145 332 145 patients, n deucravacitinib placebo 332 166 332 166 332 166 332 166 332 166 332 166 332 145 332 144 330 144 326 145 320 142 324 144 145 325 65.1% 15.1% 77.9% 73.5% figure 2. poetyk pso-1 and pso-2 study designs aapremilast was titrated from 10 mg qd to 30 mg bid over the first 5 days of dosing. bupon relapse (≥50% loss of week 24 pasi percentage improvement from baseline), patients were to be switched to deucravacitinib 6 mg qd. bid, twice daily; pasi, psoriasis area and severity index; pasi 50, ≥50% reduction from baseline in pasi; pasi 75, ≥75% reduction from baseline in pasi; qd, once daily. • by week 16, significantly greater reductions in bsa involvement were observed in patients treated with deucravacitinib (60.0%) vs those treated with placebo (11.3%; p < 0.0001) and apremilast (43.2%; p < 0.0001) (figure 3) – significantly greater reductions were also observed with deucravacitinib vs apremilast by week 24 (66.6% vs 46.1%; p < 0.0001) • bsa × spga scores followed a similar pattern, with a decrease of 72.6% at week 16 in deucravacitinib-treated patients vs 19.9% with placebo (p < 0.0001) and 55.1% with apremilast (p < 0.0001) (figure 3) – by week 24, bsa × spga involvement decreased by 76.1% in patients who received deucravacitinib vs 55.9% (p < 0.0001) in patients treated with apremilast • bsa × spga 75 response rates were significantly higher in patients treated with deucravacitinib vs those treated with placebo (p < 0.0001) and apremilast (p < 0.0001) at week 16 and vs apremilast at week 24 (p < 0.0001) (figure 4) poetyk pso-1 (n = 666) mbocf was used to impute missing data; baseline observation was carried forward for patients who discontinued due to lack of efficacy or adverse events. bsa, body surface area; bsa × spga, body surface area × static physician’s global assessment score; cfb, change from baseline; mbocf, modified baseline observation carried forward. deucravacitinib placebo to deucravacitinib bsa over 52 weeks weeks poetyk pso-2 (n = 1020) -90 -80 -70 -60 -50 -40 -30 -20 -10 0 0 1 2 4 8 12 16 20 24 28 32 36 40 44 48 52 m ea n pe rc en ta ge c fb -74.2% bsa × spga over 52 weeks weeks -21.1% -81.4% -84.4% -11.1% -75.6% -74.6% 332 patients, n 332 332 145166placebo 332 166 332 166 332 166 332 166 332 166 332 166 145 332 330 144 326 320 324 332deucravacitinib 144 145 142 144 145 325 145 figure 4. bsa × spga 75 mean response rates during poetyk pso-1/pso-2: weeks 1‒24 *p < 0.0001 vs placebo. †p < 0.0001 vs apremilast. nonresponder imputation was used to impute missing data. bsa × spga 75, ≥75% improvement from baseline in body surface area × static physician’s global assessment score. * *† * *† *† † † 68.5% 44.5% 13.3% 43.8% 62.6% patients, n deucravacitinib apremilast placebo 843 422 421 843 422 421 843 422 421 843 422 421 843 422 421 843 422 421 836 422 na 842 421 na deucravacitinib placebo apremilast deucravacitinib placebo to deucravacitinib parameter poetyk pso-1 poetyk pso-2 placebo (n = 166) deucravacitinib (n = 332) apremilast (n = 168) placebo (n = 255) deucravacitinib (n = 511) apremilast (n = 254) age, mean (sd), y 47.9 (14.0) 45.9 (13.7) 44.7 (12.1) 47.3 (13.6) 46.9 (13.4) 46.4 (13.3) weight, mean (sd), kg 89.1 (22.3) 87.9 (21.8) 87.5 (21.1) 91.5 (20.2) 92.3 (21.9) 93.5 (22.2) female, n (%) 53 (31.9) 102 (30.7) 58 (34.5) 74 (29.0) 175 (34.2) 97 (38.2) race, n (%) white 128 (77.1) 267 (80.4) 139 (82.7) 232 (91.0) 474 (92.8) 229 (90.2) asian 34 (20.5) 59 (17.8) 28 (16.7) 8 (3.1) 24 (4.7) 12 (4.7) disease duration, mean (sd), y 17.3 (12.8) 17.1 (12.4) 17.7 (11.8) 19.9 (12.8) 19.6 (12.9) 18.9 (12.4) prior systemic treatment use, n (%) biologic 63 (38.0) 130 (39.2) 66 (39.3) 83 (32.5) 165 (32.3) 79 (31.1) no prior systemic therapy 57 (34.3) 132 (39.8) 59 (35.1) 116 (45.5) 237 (46.4) 114 (44.9) spga, n (%) 3 (moderate) 128 (77.1) 257 (77.4) 139 (82.7) 217 (85.1) 408 (79.8) 196 (77.2) 4 (severe) 37 (22.3) 75 (22.6) 29 (17.3) 38 (14.9) 103 (20.2) 58 (22.8) pasi, mean (sd) 20.7 (8.0) 21.8 (8.6) 21.4 (9.0) 21.1 (9.0) 20.7 (7.5) 21.6 (8.4) bsa, mean (sd), % 25.3 (16.9) 26.6 (15.9) 26.6 (16.1) 25.3 (15.7) 26.3 (15.8) 28.3 (16.5) bsa × spga, mean (sd) 82.1 (57.3) 86.9 (56.1) 85.4 (54.9) 81.1 (56.3) 85.0 (54.6) 92.4 (58.7) dlqi, mean (sd) 11.4 (6.6) 12.0 (6.7) 12.4 (6.8) 11.8 (6.8) 11.8 (6.5) 12.5 (6.7) pssd symptom score, mean (sd) 51.4 (26.8) 51.7 (25.2) 56.2 (25.2) 50.1 (24.8) 52.3 (26.3) 51.9 (25.4) bsa, body surface area; bsa × spga, body surface area × static physician's global assessment score; dlqi, dermatology life quality index; pasi, psoriasis area and severity index; pssd, psoriasis symptoms and signs diary. table 1. baseline patient demographics and disease characteristics scientific content on demand to request a copy of this poster: scan qr code via a barcode reader application qr codes are valid for 30 days after congress presentation date slide number 1 powerpoint presentation achievement of the national psoriasis foundation treatment treat-to-target goals in the us ixekizumab customer support program key eligibility criteria ■ patients with psoriasis enrolled in the us ixekizumab csp ■ ≥18 years of age ■ commercial insurance ■ initiated ixekizumab within 7 days of screening ■ device with access to the internet assessments ■ web-based questionnaires administered at baseline, weeks 2, 4, 8, 12, and 24 ■ body surface area (bsa) measured by prepi questionnaire – prepi: single question in which the patient estimates how many palms of the hand are needed to cover psoriasis patches on the body – a palm of the patient’s hand is ~ 1% bsa ■ psoriatic arthritis diagnosis is self-reported alice b. gottlieb1, russel burge2, william n. malatestinic2, baojin zhu2, yunyang zhao2, julie mccormack3, miriam kimel3, meghan feely2, joseph f. merola4 1icahn school of medicine at mount sinai, new york, usa; 2eli lilly and company, indianapolis, usa; 3evidera, bethesda, usa; and 4harvard medical school, brigham and women’s hospital, boston, usa methods us ixekizumab csp design patient demographics and baseline characteristics disclosures  a. b. gottlieb has received honoraria as an advisory board member, non-promotional speaker or consultant for: amgen, anaptysbio, avotres therapeutics, boehringer ingelheim, bristol myers squibb, dice therapeutics, dermavant, eli lilly, janssen, novartis, pfizer, sanofi, sun pharma, ucb pharma, and xbiotech (stock options for an ra project); research/educational grants from: anaptysbio, janssen, novartis, ortho dermatologics, sun pharma, bms, and ucb pharma; all funds go to the icahn school of medicine at mount sinai; r. burge, w. n. malatestinic, b. zhu, y. zhao, m. feely are shareholders and employees of: eli lilly and company; m. feely is a clinical instructor at: mount sinai hospital and has received consulting, travel, or speaker fees from: aerolase, castle biosciences, galderma aesthetics, glow recipe, la roche-posay l'oréal, revian, sonoma pharmaceuticals, sun pharma, and suneva medical; j. mccormack and m. kimel declare no conflicts of interest; j. f. merola is a consultant and/or investigator for: abbvie, amgen, biogen, bristol myers squibb, dermavant, eli lilly and company, janssen, leo pharma, novartis, pfizer, sanofi regeneron, sun pharma, and ucb pharma  this study was sponsored by eli lilly and company. medical writing services were provided by molly tomlin, ms, med, of eli lilly and company references 1. armstrong aw, et al. j am acad dermatol. 2017;76(2):290-8 2. armstrong a, et al. j am acad dermatol. 2021; 85(2): 330-336 target response (n=422) acceptable response (n= 294) age, mean ± sd 46.7 ± 12.1 46.1 ± 11.8 women, n (%) 266 (63%) 179 (61%) duration from onset of psoriasis, months, mean ± sd 193.8 ± 164.9 205.3 ± 165.9 baseline bsa, mean ± sd 11.7 ± 16.3 15.8 ± 18.0 psoriasis locations, n (%) scalp psoriasis 276 (65%) 206 (70%) genital psoriasis 105 (25%) 81 (28%) nail psoriasis 116 (27%) 87 (30%) psoriatic arthritis, n (%) 211 (50%) 144 (49%) bio-experienced (previous 2 years), n (%) 178 (42%) 124 (42%) study was sponsored by eli lilly and company background ■ the national psoriasis foundation (npf) has defined treatment goals to improve patient care in psoriasis1 – the goals establish targets to inform treatment decisions, reduce disease burden, and improve patient outcomes in clinical practice ■ the real-world effectiveness of ixekizumab, a highly selective il17a monoclonal antibody, has been evaluated in patients with moderate-to-severe psoriasis in the taltz customer support program (csp) objective ■ to evaluate the real-world effectiveness of patients initiating ixekizumab to achieve npf-defined treat-to-target goals after 12 weeks of treatment with data from the csp key results discussion  although bsa was measured differently (patient vs. clinical assessment) the findings for target and acceptable responses in this real-world study were similar to those seen in the uncover phase iii clinical trials2 − with a real-world study population, factors influencing outcomes may also include, but are not limited to, compliance with medications, and experience with biologics conclusions ■ the results from this study provide evidence of the realworld effectiveness of ixekizumab; observations from the overall sample were similar to those across the subgroups, psa and biologic use winter clinical dermatology conference (wcdc); kohala coast, usa; 13-18 january 2023 percentage of patients achieving npf target and acceptable response after 12 weeks of treatment scan or click the qr code or use this url (https://lillyscience.lilly.com/congress/wcdc2023) for a list of all lilly content presented at the congress. other company and product names are trademarks of their respective owners. abbreviations bsa=body surface area; csp=customer support program; dlqi=dermatology life quality index; ixe=ixekizumab; npf=national psoriasis foundation; nrs=numeric rating scale; patga=patient’s global assessment; prepi=patient-reported extent of psoriasis involvement; psa=psoriatic arthritis; pso=psoriasis; sd=standard deviation npf treatment goals1 ■ at 12 weeks after treatment initiation − target response: bsa ≤1% − acceptable response: bsa ≤3% or improvement in bsa ≥75% from baseline statistical analyses ■ descriptive analyses with observed data ■ inclusion in the study population – target response: patients were required to have bsa >1% at baseline – acceptable response: patients were required to have a baseline bsa >3% percentage of patients achieving npf target and acceptable response after 12 weeks of treatment by bio-experience percentage of patients achieving npf target and acceptable response after 12 weeks of treatment by psoriatic arthritis 0 10 20 30 40 50 60 70 80 90 100 75.0 55.0 r es po ns e (% ) target response (n=303) acceptable response (n=213) for target response, analyses included patients with a baseline bsa score >1 and non-missing bsa score at week 12 for acceptable response, analyses included patients with a baseline bsa score >3 and non-missing bsa score at week 12 0 10 20 30 40 50 60 70 80 90 100 73.0 77.0 57.0 52.0 r es po ns e (% ) bionaive (n=167) bionaive (n=120) bioexperienced (n=136) bioexperienced (n=93) target response acceptable response 0 10 20 30 40 50 60 70 80 90 100 75.0 75.0 54.0 56.0 r es po ns e (% ) with psa (n=154) with psa (n=106) pso only (n=149) pso only (n=107) target response acceptable response slide number 1 powerpoint presentation primary outcome: modified spga-g response (score 0 [clear] or 1 [almost clear] with a ≥ 2-point reduction from baseline) to assess genital psoriasis severity at week 16 presented at: winter clinical dermatology conference hawaii 2023; january 13–18, 2023; hi, usa © 2023 amgen inc. efficacy and safety of apremilast in patients with genital psoriasis: results from the phase 3, randomized, placebo-controlled, double-blind discreet study joseph f. merola, md, mmsc1; lawrence charles parish, md, md (hons)2; lyn guenther, md3; charles lynde, md4,5; jean-philippe lacour, md6; petra staubach, md7; sue cheng, md, phd8; shauna jardon, pharmd8; maria paris, md8; mindy chen, ms8; kim papp, md, phd9,10 what do we know? what did we do? what were our findings at week 16? key takeaways apremilast, the first oral treatment to be studied for genital psoriasis, significantly improved disease symptoms, including skin, itch, and qol and was well-tolerated in patients who were inadequately controlled by or intolerant to medications applied to the skin for additional findings, scan the qr code 1brigham and women’s hospital, harvard medical school, boston, ma, usa; 2parish dermatology, philadelphia, pa, usa; 3guenther research inc., london, on, canada; 4lynde institute for dermatology, markham, on, canada; 5probity medical research, markham, on, canada; 6chu de nice hôpital l'archet, nice, france; 7department of dermatology, university medical center, mainz, germany; 8amgen inc., thousand oaks, ca, usa; 9probity medical research, waterloo, on, canada; 10k papp clinical research, waterloo, on, canada up to 63% of patients with psoriasis report genital psoriasis,1,2 which can lead to: • itching • discomfort • impaired qol • negative impact on sexual health patient population: • genital psoriasis severity (modified spga-g) score ≥ 3 • overall psoriasis severity (spga) score ≥ 3 • nongenital plaque psoriasis on ≥ 1% of bsa • intolerant to/or not controlled by medications applied to the skin for genital psoriasis phase 3, multicenter study week 36 1: 1 fo llo w -u p week 16 placebo apremilast week 32 apremilast apremilast week 0 143 patients 146 patients 289 patients randomized key secondary outcomes: • spga response to assess overall psoriasis severity • gpi-nrs response to assess genital itch severity • change from baseline in dlqi score to assess the impact of psoriasis on qol at week 16 no new safety signals were identified, and adverse events were consistent with the known apremilast safety profile all outcomes at week 16 improved with apremilast vs placebo apremilast, n = 143 70% male; mean age: 44 years genital psoriasis duration: 11 years dlqi: 13.3 spga-g: 86% moderate; 14% severe placebo, n = 146 70% male; mean age: 46 years genital psoriasis duration: 12 years dlqi: 12.8 spga-g: 88% moderate; 12% severe baseline characteristics were similar between treatment groups apremilast, an oral immunomodulator, is approved in adults with psoriasis, psoriatic arthritis, and oral ulcers associated with behçet’s disease references: 1. ryan c, et al. j am acad dermatol. 2015;72:978-983. 2. meeuwis kap, et al. j dermatol treat. 2018;29:754-760. abbreviations: bsa, body surface area; dlqi, dermatology life quality index; gpi-nrs, genital psoriasis itch numeric rating scale; qol, quality of life; spga, static physician global assessment; spga-g, static physician global assessment of genitalia. disclosures and funding statement: jfm: abbvie, amgen, biogen, bristol myers squibb, dermavant, eli lilly, janssen, leo pharma, novartis, pfizer, regeneron, sanofi, sun pharmaceuticals, and ucb – consultant and/or investigator. lcp: abbvie, alfasigma, amgen, amytrx, eli lilly, bristol myers squibb, fibrocell, galderma, glaxosmithkline, kiniksa, olix, oneness, pfizer, trevi, and ucb – investigator. lg: abbvie, amgen, bausch health, bristol myers squibb, celgene, eli lilly, galderma, janssen, leo pharma, merck frosst, pfizer, sun pharmaceuticals, and ucb – consultant, investigator, and/or speaker. amgen, bausch, eli lilly, janssen, leo pharma, pfizer, and sun pharmaceuticals – speaker, consultant, and grant/research support. abbvie, boehringer ingelheim, bristol myers squibb, celgene, galderma, merck frosst, and ucb pharma – grant/research support. cl: abbvie, boehringer ingelheim, celgene, eli lilly, janssen, merck, novartis, pfizer, sun pharma, and valeant – principal investigator/consultant. j-pl: abbvie, amgen, boehringer ingelheim, dermira, janssen, leo pharma, and pfizer – grants and personal fees. celgene, galderma, eli lilly, novartis and sanofi – grant/research support. ps: abbvie, allergika, almirall hermal, amgen, beiersdorf, biocryst, bristol myers squibb, boehringer ingelheim, celgene, csl behring, eli lilly, galderma, hexal, janssen, klinge, leo pharma, leti pharma, l´oreal, neubourg, novartis, octapharma, pfizer, pflüger, pharming, regeneron, shire, takeda, regeneron, sanofi genzyme, and ucb pharma – grants. sc, sj, mp, and mc: amgen inc. – employees and stockholders. kp: abbvie, actelion, amgen, astellas pharma us, boehringer ingelheim, bausch health, celgene corporation, dermira, dow pharmaceuticals, eli lilly, frontier, galderma, janssen, kyowa hakko kirin pharma, leo pharma, medimmune, merck & co., inc., novartis, pfizer, regeneron, roche laboratories, sanofi genzyme, takeda pharmaceuticals, ucb, and valeant – honoraria, grants, and/or research funding as a speaker, investigator, advisory board member, data safety monitoring board member, and/or consultant; psloar, pure – steering committee member. this study was funded by amgen inc. writing support was funded by amgen inc. and provided by archana patkar, phd, of cactus life sciences (part of cactus communications) and dawn nicewarner, phd, cmpp, employee of and stockholder in amgen inc.. what was our aim? to evaluate the benefit, safety, tolerability, and effect on health-related qol of apremilast in patients with moderate to severe genital psoriasis after 16 weeks of treatment in the discreet study (nct03777436) limited treatment options are available for patients with moderate to severe genital psoriasis 3x 2x 2x 2x genital psoriasis severity (spga-g response rate) overall psoriasis severity (spga response rate) genital itch (gpi-nrs response rate) qol (reduction in dlqi score from baseline) 38.7% vs 19.1% 21.5% vs 7.2% 46.0% vs 19.6% –5.3 vs –2.6 apremilast placebovs slide number 1 deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, in moderate to severe plaque psoriasis: efficacy by baseline body surface area (bsa) involvement and baseline psoriasis area and severity index (pasi) april w armstrong,1 mark lebwohl,2 jerry bagel,3 todd schlesinger,4 subhashis banerjee,5 renata m kisa,5 thomas scharnitz,5 kim hoyt,5 bruce strober6 1university of southern california, los angeles, ca, usa; 2icahn school of medicine at mount sinai, new york, ny, usa; 3psoriasis treatment center of new jersey, east windsor, nj, usa; 4clinical research center of the carolinas, charleston, sc, usa; 5bristol myers squibb, princeton, nj, usa; 6yale university school of medicine, new haven, and central connecticut dermatology research, cromwell, ct, usa presented at the winter clinical dermatology conference hawaii®, january 13-18, 2023, kohala coast, hi, and winter clinical miamitm, february 17-20, 2023, miami, fl email: aprilarmstrong@post.harvard.edu copies of this poster are for personal use only and may not be reproduced without written permission from the authors. introduction • tyrosine kinase 2 (tyk2) is an intracellular enzyme that mediates signaling of cytokines (interleukin-23 and type i interferons) involved in psoriasis pathogenesis (figure 1)1,2 • deucravacitinib, an oral, selective, allosteric tyk2 inhibitor, is approved in the us and other countries for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy3 figure 1. mechanism of action of deucravacitinib tyk2 deucravacitinib (allosteric inhibitor class) unique regulatory domain catalytic domain (highly conserved across jak family) atp-binding active site (approved jak inhibitor class) •  ≥100-fold greater selectivity for tyk2 vs jak 1/3 • ≥2000-fold greater selectivity for tyk2 vs jak 2 selectivity in cells1,2: atp, adenosine triphosphate; jak, janus kinase; tyk2, tyrosine kinase 2. • in 2 pivotal, multinational phase 3 trials, poetyk pso-1 (nct03624127) and pso-2 (nct03611751), in patients with moderate to severe plaque psoriasis, deucravacitinib treatment was associated with: — significantly greater response rates for ≥75% reduction from baseline in psoriasis area and severity index (pasi 75) and static physician’s global assessment score of 0 (clear) or 1 (almost clear) with a ≥2-point improvement from baseline (spga 0/1) at week 16 vs placebo and apremilast4,5 — maintenance of clinical efficacy was seen through week 52 with continuous deucravacitinib treatment6 objective • to examine the efficacy of deucravacitinib in patients with moderate to severe plaque psoriasis based on baseline body surface area (bsa) involvement and pasi score methods • adult patients with moderate to severe plaque psoriasis (pasi ≥12, spga ≥3, bsa involvement ≥10%) were randomized 1:2:1 to placebo, oral deucravacitinib 6 mg once daily, or apremilast 30 mg twice daily (figure 2) • blinded treatment switches occurred at week 16 and week 24 — patients randomized to placebo crossed over to deucravacitinib at week 16 — patients randomized to apremilast who failed to meet trial-specific efficacy thresholds (≥50% reduction from baseline in pasi [pasi 50] in poetyk pso-1; pasi 75 in poetyk pso-2) switched to deucravacitinib at week 24 figure 2. poetyk pso-1 and pso-2 study designs coprimary endpoints: pasi 75 and spga 0/1 for deucravacitinib vs placebo at week 16 poetyk pso-1 (n = 666) deucravacitinib 6 mg qdplacebo (n = 166) deucravacitinib 6 mg qd<pasi 50 apremilast 30 mg bid≥pasi 50 titrate* 1 :2 :1 r an d om iz at io n weeks 16 24 520 deucravacitinib 6 mg qd (n = 332) primary endpoint apremilast 30 mg bida (n = 168) poetyk pso-2 (n = 1020) deucravacitinib 6 mg qdplacebo (n = 255) deucravacitinib 6 mg qd (n = 511) deucravacitinib 6 mg qd deucravacitinib 6 mg qd deucravacitinib 6 mg qd deucravacitinib 6 mg qd placebob apremilast 30 mg bida (n = 254) 1 :2 :1 r an d om iz at io n weeks 16 24 520 1:1 deucravacitinib 6 mg qdplacebob primary endpoint <pasi 75 ≥pasi 75 <pasi 75 ≥pasi 75 from armstrong aw, et al. deucravacitinib versus placebo and apremilast in moderate to severe plaque psoriasis: efficacy and safety results from the 52-week, randomized, double-blinded, placebo-controlled phase 3 poetyk pso-1 trial. j am acad dermatol. 2023;88:29-39. this work is licensed under a creative commons attribution license (cc by-nc-nd 4.0). https://creativecommons.org/licenses/by-nc-nd/4.0/. from strober b, et al. deucravacitinib versus placebo and apremilast in moderate to severe plaque psoriasis: efficacy and safety results from the 52-week, randomized, double-blinded, phase 3 poetyk pso-2 trial. j am acad dermatol. 2023;88:40-51. this work is licensed under a creative commons attribution license (cc by-nc-nd 4.0). https://creativecommons.org/licenses/by-nc-nd/4.0/. aapremilast was titrated from 10 mg qd to 30 mg bid over the first 5 days of dosing. bupon relapse (≥50% loss of week 24 pasi percentage improvement from baseline), patients were to be switched to deucravacitinib 6 mg qd. bid, twice daily; pasi, psoriasis area and severity index; pasi 50, ≥50% reduction from baseline in pasi; pasi 75, ≥75% reduction from baseline in pasi; qd, once daily; spga 0/1, static physician's global assessment score of 0 (clear) or 1 (almost clear) with a ≥2-point improvement from baseline. • analysis populations: — pooled poetyk pso-1 and pso-2: all patients treated with deucravacitinib or apremilast through week 24 and patients treated with placebo through week 16 — continuous deucravacitinib treatment from baseline: patients in the poetyk pso-1 trial who received continuous deucravacitinib from day 1 through week 52 — placebo crossovers: patients in the poetyk pso-1 trial who crossed over to deucravacitinib treatment at week 16 through week 52 • efficacy was assessed using the achievement of pasi 75 and spga 0/1 in the following subgroups using nonresponder imputation (nri): — baseline bsa involvement: 10%–<15%, 15%–<20%, 20%–<30%, ≥30% — baseline pasi score: 12–<15, ≥15 • analyses were descriptive; no statistical analyses were performed results baseline demographics • baseline patient demographics were largely comparable across treatment groups and bsa/pasi subgroups in the pooled populations of both trials (table 1) and in the poetyk pso-1 population alone (table 2) table 1. baseline demographics by baseline bsa involvement and pasi score in the pooled poetyk pso-1 and pso-2 population baseline bsa involvement baseline pasi score parameters 10%–<15% 15%–<20% 20%–<30% ≥30% 12–<15 ≥15 placebo (n = 105) deucravacitinib (n = 194) apremilast (n = 92) placebo (n = 104) deucravacitinib (n = 183) apremilast (n = 84) placebo (n = 92) deucravacitinib (n = 198) apremilast (n = 101) placebo (n = 120) deucravacitinib (n = 268) apremilast (n = 145) placebo (n = 110) deucravacitinib (n = 183) apremilast (n = 94) placebo (n = 310) deucravacitinib (n = 660) apremilast (n = 328) age, mean (sd), y 48.4 (13.8) 46.9 (14.4) 47.0 (12.0) 47.2 (14.5) 47.2 (12.8) 45.5 (12.3) 48.7 (14.0) 45.6 (13.5) 45.2 (13.0) 46.2 (12.8) 46.4 (13.4) 45.5 (13.6) 47.3 (14.4) 47.2 (13.1) 44.9 (12.0) 47.7 (13.5) 46.3 (13.6) 46.0 (13.1) weight, mean (sd), kg 88.5 (19.8) 88.7 (22.9) 88.9 (19.1) 89.2 (20.9) 91.1 (22.1) 88.5 (17.7) 92.9 (20.7) 91.9 (22.2) 89.0 (21.7) 91.8 (22.6) 90.5 (20.9) 95.4 (25.3) 91.8 (19.9) 87.0 (21.9) 90.1 (21.4) 90.2 (21.5) 91.5 (21.8) 91.4 (22.1) bmi, mean (sd), kg/m2 29.7 (6.4) 30.1 (7.0) 30.1 (6.3) 30.1 (6.1) 30.4 (7.2) 30.1 (5.9) 31.3 (6.7) 31.1 (6.9) 30.1 (6.9) 30.3 (7.5) 30.4 (6.6) 32.1 (8.1) 30.5 (6.4) 29.7 (7.3) 30.9 (6.9) 30.3 (6.9) 30.8 (6.7) 30.8 (7.1) female, n (%) 38 (36.2) 72 (37.1) 40 (43.5) 34 (32.7) 59 (32.2) 32 (38.1) 30 (32.6) 72 (36.4) 34 (33.7) 25 (20.8) 74 (27.6) 49 (33.8) 34 (30.9) 69 (37.7) 43 (45.7) 93 (30.0) 208 (31.5) 112 (34.1) race, n (%) white 87 (82.9) 173 (89.2) 80 (87.0) 92 (88.5) 164 (89.6) 75 (89.3) 82 (89.1) 165 (83.3) 86 (85.1) 99 (82.5) 239 (89.2) 127 (87.6) 97 (88.2) 161 (88.0) 78 (83.0) 263 (84.8) 580 (87.9) 290 (88.4) asian 10 (9.5) 17 (8.8) 11 (12.0) 8 (7.7) 15 (8.2) 4 (4.8) 6 (6.5) 26 (13.1) 12 (11.9) 18 (15.0) 25 (9.3) 13 (9.0) 8 (7.3) 19 (10.4) 15 (16.0) 33 (10.6) 64 (9.7) 25 (7.6) other 8 (7.6) 4 (2.1) 1 (1.1) 4 (3.8) 4 (2.2) 5 (6.0) 4 (4.3) 7 (3.5) 3 (3.0) 3 (2.5) 4 (1.5) 5 (3.4) 5 (4.5) 3 (1.6) 1 (1.1) 14 (4.5) 16 (2.4) 13 (4.0) bmi, body mass index; bsa, body surface area; pasi, psoriasis area and severity index; sd, standard deviation. table 2. baseline demographics by baseline bsa involvement and pasi score in the poetyk pso-1 population baseline bsa involvement baseline pasi score parameters 10%–<15% 15%–<20% 20%–<30% ≥30% 12–<15 ≥15 placebo deucravacitinib (n = 36) deucravacitinib (n = 61) placebo deucravacitinib (n = 36) deucravacitinib (n = 73) placebo deucravacitinib (n = 20) deucravacitinib (n = 70) placebo deucravacitinib (n = 48) deucravacitinib (n = 98) placebo deucravacitinib (n = 40) deucravacitinib (n = 64) placebo deucravacitinib (n = 100) deucravacitinib (n = 238) age, mean (sd), y 48.0 (14.0) 46.6 (15.1) 51.3 (14.5) 47.6 (13.9) 50.2 (16.3) 43 (13.6) 43.5 (11.9) 46.8 (13.0) 46.3 (14.6) 46.7 (13.4) 48.2 (13.9) 45.9 (14.0) weight, mean (sd), kg 89.9 (19.5) 88.2 (22.3) 89.2 (22.4) 88.5 (23.0) 88.8 (22.3) 85.8 (22.4) 86.7 (24.9) 86.9 (20.9) 91.9 (20.5) 84.3 (20.6) 87.1 (23.0) 88.1 (22.3) bmi, mean (sd), kg/m2 30.1 (6.2) 30.0 (7.1) 30.4 (6.6) 30.1 (8.1) 30.6 (7.8) 29.5 (7.5) 29.2 (8.1) 29.3 (6.0) 30.2 (6.4) 29.3 (8.0) 29.8 (7.5) 29.8 (6.8) female, n (%) 12 (33.3) 25 (41.0) 11 (30.6) 24 (32.9) 11 (55.0) 24 (34.3) 12 (25.0) 24 (24.5) 12 (30.0) 27 (42.2) 34 (34.0) 70 (29.4) race, n (%) white 31 (86.1) 52 (85.2) 28 (77.8) 61 (83.6) 16 (80.0) 50 (71.4) 33 (68.8) 79 (80.6) 34 (85.0) 52 (81.3) 74 (74.0) 190 (79.8) asian 5 (13.9) 8 (13.1) 6 (16.7) 11 (15.1) 4 (20.0) 18 (25.7) 14 (29.2) 18 (18.4) 5 (12.5) 12 (18.8) 24 (24.0) 43 (18.1) other 0 1 (1.6) 2 (5.6) 1 (1.4) 0 2 (2.9) 1 (2.1) 1 (1.0) 1 (2.5) 0 2 (2.0) 5 (2.1) bmi, body mass index; bsa, body surface area; pasi, psoriasis area and severity index; sd, standard deviation. efficacy: pooled poetyk pso-1/pso-2 population • pasi 75 and spga 0/1 response rates were similar across baseline bsa involvement and pasi score subgroups, regardless of treatment type (figures 3-6) • patients treated with deucravacitinib achieved numerically higher pasi 75 and spga 0/1 vs patients treated with placebo or apremilast at week 16 and vs apremilast at week 24, regardless of baseline bsa involvement or pasi score figure 3. pasi 75 response rates at weeks 16 and 24 by baseline bsa involvement in the pooled poetyk pso-1 and pso-2 population (nri) 0 10 20 30 40 50 60 70 80 90 100 deucravacitinib deucravacitinibplaceboa apremilast apremilast 10%–<15% 15%–<20% 20%–<30% ≥30% week 16 week 24 r e sp o n se r at e , % n= 105 194 92 193 92104 183 84 182 8419892 101 195 101145268120 145266 10%–<15% 15%–<20% 20%–<30% ≥30% 10%–<15% 15%–<20% 20%–<30% ≥30% apatients crossed over from placebo to deucravacitinib at week 16; therefore, no placebo patients are included at week 24. bsa, body surface area; nri, nonresponder imputation; pasi 75, ≥75% reduction from baseline in psoriasis area and severity index. figure 4. pasi 75 response rates at weeks 16 and 24 by baseline pasi score in the pooled poetyk pso-1 and pso-2 population (nri) 0 10 20 30 40 50 60 70 80 90 100 deucravacitinib deucravacitinibplaceboa apremilast apremilast 12–<15 ≥15 week 16 week 24 r e sp o n se r at e , % n= 110 183 94 182 94328660310 328654 12–<15 ≥15 12–<15 ≥15 apatients crossed over from placebo to deucravacitinib at week 16; therefore, no placebo patients are included at week 24. nri, nonresponder imputation; pasi, psoriasis area and severity index; pasi 75, ≥75% reduction from baseline in pasi. figure 5. spga 0/1 response rates at weeks 16 and 24 by baseline bsa involvement in the pooled poetyk pso-1 and pso-2 population (nri) 0 10 20 30 40 50 60 70 80 90 100 deucravacitinib deucravacitinibplaceboa apremilast apremilast 10%–<15% 15%–<20% 20%–<30% ≥30% week 16 week 24 r e sp o n se r at e , % n= 105 194 92 193 92104 183 84 182 8419892 101 195 101145268120 145266 10%–<15% 15%–<20% 20%–<30% ≥30% 10%–<15% 15%–<20% 20%–<30% ≥30% apatients crossed over from placebo to deucravacitinib at week 16; therefore, no placebo patients are included at week 24. bsa, body surface area; nri, nonresponder imputation; spga 0/1, static physician’s global assessment score of 0 (clear) or 1 (almost clear) with a ≥2-point improvement from baseline. figure 6. spga 0/1 response rates at weeks 16 and 24 by baseline pasi score in the pooled poetyk pso-1 and pso-2 population (nri) 0 10 20 30 40 50 60 70 80 90 100 deucravacitinib deucravacitinibplaceboa apremilast apremilast 12–<15 ≥15 week 16 week 24 r e sp o n se r at e , % n= 110 183 94 182 94328660310 328654 12–<15 ≥15 12–<15 ≥15 apatients crossed over from placebo to deucravacitinib at week 16; therefore, no placebo patients are included at week 24. nri, nonresponder imputation; pasi, psoriasis area and severity index; spga 0/1, static physician’s global assessment score of 0 (clear) or 1 (almost clear) with a ≥2-point improvement from baseline. efficacy: poetyk pso-1 population • pasi 75 and spga 0/1 response rates were similar across baseline bsa involvement and pasi score subgroups at weeks 16, 24, and 52 in patients treated with continuous deucravacitinib from day 1 (figures 7-10) • by week 52, patients who crossed over from placebo to deucravacitinib at week 16 achieved results similar to patients treated continuously with deucravacitinib from day 1, regardless of baseline bsa involvement or pasi score subgroup figure 7. pasi 75 response rates at weeks 16, 24, and 52 with continuous treatment from day 1 by baseline bsa involvement in poetyk pso-1 (nri) 0 10 20 30 40 50 60 70 80 90 100 10%–<15% 15%–<20% 20%–<30% ≥30% r e sp o n se r at e , % n= deucravacitinibplacebo week 16 36 6136 73 7020 9848 deucravacitinibplacebodeucravacitinib week 24 36 6136 73 7020 9848 deucravacitinibplacebodeucravacitinib week 52 36 6136 73 7020 9848 10%–<15% 15%–<20% 20%–<30% ≥30% bsa, body surface area; nri, nonresponder imputation; pasi 75, ≥75% reduction from baseline in psoriasis area and severity index. figure 8. pasi 75 response rates at weeks 16, 24, and 52 with continuous treatment from day 1 by baseline pasi score in poetyk pso-1 (nri) 0 10 20 30 40 50 60 70 80 90 100 12–<15 ≥15 r e sp o n se r at e , % n= deucravacitinibplacebo week 16 40 64 238100 deucravacitinibplacebodeucravacitinib week 24 40 64 238100 deucravacitinibplacebodeucravacitinib week 52 40 64 238100 12–<15 ≥15 nri, nonresponder imputation; pasi, psoriasis area and severity index; pasi 75, ≥75% reduction from baseline in pasi. figure 9. spga 0/1 response rates at weeks 16, 24, and 52 with continuous treatment from day 1 by baseline bsa involvement in poetyk pso-1 (nri) 0 10 20 30 40 50 60 70 80 90 100 10%–<15% 15%–<20% 20%–<30% ≥30% r e sp o n se r at e , % n= deucravacitinibplacebo week 16 36 6136 73 7020 9848 deucravacitinibplacebodeucravacitinib week 24 36 6136 73 7020 9848 deucravacitinibplacebodeucravacitinib week 52 36 6136 73 7020 9848 10%–<15% 15%–<20% 20%–<30% ≥30% bsa, body surface area; nri, nonresponder imputation; spga 0/1, static physician’s global assessment score of 0 (clear) or 1 (almost clear) with a ≥2-point improvement from baseline. figure 10. spga 0/1 response rates at weeks 16, 24, and 52 with continuous treatment from day 1 by baseline pasi score in poetyk pso-1 (nri) 0 10 20 30 40 50 60 70 80 90 100 12–<15 ≥15 r e sp o n se r at e , % n= deucravacitinibplacebo week 16 40 64 238100 deucravacitinibplacebodeucravacitinib week 24 40 64 238100 deucravacitinibplacebodeucravacitinib week 52 40 64 238100 12–<15 ≥15 nri, nonresponder imputation; pasi, psoriasis area and severity index; spga 0/1, static physician’s global assessment score of 0 (clear) or 1 (almost clear) with a ≥2-point improvement from baseline. conclusions • deucravacitinib improved pasi 75 and spga 0/1 responses to a similar extent regardless of baseline bsa involvement or pasi score • improved efficacy responses were seen by week 16 with deucravacitinib treatment vs placebo or apremilast • responses with deucravacitinib were overall numerically higher at week 24 vs week 16 • responses were maintained through week 52 in patients receiving continuous deucravacitinib from day 1 and improved in patients receiving placebo who crossed over to deucravacitinib at week 16 references 1. burke jr, et al. sci transl med. 2019;11:eaaw1736. 2. wrobleski st et al. j med chem. 2019;62:8973-8995. 3. sotyktutm (deucravacitinib) [package insert]. princeton, nj: bristol-myers squibb company; september 2022. 4. armstrong aw, et al. j am acad dermatol. 2023;88:29-39. 5. strober b, et al. j am acad dermatol. 2023;88:40-51. 6. warren rb, et al. presented at the eadv 30th congress; september 29-october 2, 2021. acknowledgments • this study was sponsored by bristol myers squibb • writing and editorial assistance was provided by nick cianciola, phd, cmpp, of peloton advantage, llc, an open health company, parsippany, nj, usa, funded by bristol myers squibb disclosures • awa: grants and personal fees: abbvie, bristol myers squibb, eli lilly, janssen, leo pharma, and novartis; personal fees: boehringer ingelheim/parexel, celgene, dermavant, genentech, glaxosmithkline, menlo therapeutics, merck, modernizing medicine, ortho dermatologics, pfizer, regeneron, sanofi genzyme, science 37, sun pharma, and valeant; grants: dermira, kyowa hakko kirin, and ucb, outside the submitted work • ml: research funds on behalf of mount sinai: abbvie, amgen, arcutis, avotres, boehringer ingelheim, dermavant, eli lilly, incyte, janssen, ortho dermatologics, regeneron, and ucb; consultant: aditum bio, almirall, altrubio, anaptysbio, arcutis, arena, aristea, arrive technologies, avotres, biomx, boehringer ingelheim, brickell biotech, bristol myers squibb, cara therapeutics, castle biosciences, corevitas’ (corrona) psoriasis registry, dermavant, dr reddy’s laboratories, evelo biosciences, evommune, forte biosciences, helsinn therapeutics, hexima, leo pharma, meiji seika pharma, mindera, pfizer, seanergy, and verrica • jb: research funds payable to the psoriasis treatment center of new jersey: abbvie, amgen, arcutis, boehringer ingelheim, bristol myers squibb, celgene, corevitas' (corrona) psoriasis registry, dermavant, dermira/ucb, eli lilly, glenmark, janssen biotech, kadmon, leo pharma, lycera, menlo therapeutics, novartis, pfizer, regeneron, sun pharma, taro, and valeant; consultant: abbvie, amgen, celgene, eli lilly, janssen biotech, novartis, sun pharma, and valeant; speaker: abbvie, celgene, eli lilly, janssen biotech, and novartis • ts: grants or research funding: abbvie, aclaris therapeutics, akros pharma, allergan, almirall, aobiome therapeutics, arcutis, astellas pharma us, bioderma laboratories, biofrontera, biopharmx, boehringer ingelheim, bristol myers squibb, cara therapeutics, castle biosciences, celgene, chemocentryx, coherus biosciences, corevitas' (corrona) psoriasis registry, dermavant, dermira, dt collagen and dt pharmacy, eli lilly, galderma, genentech, janssen/centocor, ortho biotech, kinex, kiniksa, leo pharma, merz, novartis, pfizer, regeneron, sanofi genzyme, sisaf, tetraderm group, and trevi; consultant: abbvie, allergan, almirall, arcutis, biofrontera, bristol myers squibb, castle biosciences, eli lilly, epi health, evolus, galderma, leo pharma, merz, novartis, ortho dermatologics, pfizer, prolacta bioscience, regeneron, sisaf, sun pharma, and ucb; speakers bureaus: almirall, bristol myers squibb, dermira (now lilly), dusa, epi health, regeneron, sanofi aventis, sanofi genzyme, and sun pharma; advisory boards: allergan, almirall, bioderma laboratories, biofrontera, celgene, greenway therapeutix, and remedly • sb, rmk, and ts: employees and shareholders: bristol myers squibb • kh: consultant: bristol myers squibb • bs: consultant (honoraria): abbvie, almirall, amgen, arcutis, arena, aristea, asana, boehringer ingelheim, bristol myers squibb, connect biopharma, dermavant, eli lilly, equillium, glaxosmithkline, immunic, janssen, leo pharma, maruho, meiji seika pharma, mindera, novartis, ortho dermatologics, pfizer, regeneron, sanofi genzyme, sun pharma, ucb, ventyx biosciences, and vtv therapeutics; speaker: abbvie, eli lilly, janssen, and sanofi genzyme; co-scientific director (consulting fee): corevitas' (corrona) psoriasis registry; investigator: abbvie, cara therapeutics, corevitas' (corrona) psoriasis registry, dermavant, dermira, and novartis adelaide hebert,1 evan a rieder,2 emmy graber3 hilary baldwin,4 julie c. harper,5 linda stein gold,6 leon kircik,7 andrew f. alexis,8 james del rosso,9 siva narayanan,10 volker koscielny,11 ismail kasujee,11 richard g. fried12 1uthealth mcgovern medical school, houston, tx; 2new york university grossman school of medicine, new york, ny; 3the dermatology institute of boston and northeastern university, boston, ma; 4acne treatment and research center, brooklyn, ny; 5the dermatology and skin care center of birmingham, birmingham, al; 6henry ford health system, bloomfield, mi; 7icahn school of medicine, mount sinai, new york, ny; 8weill cornell medical college, new york, ny; 9jdr dermatology research/thomas dermatology, las vegas, nv; 10avant health llc, bethesda, md; 11almirall sa, barcelona, spain; 12yardley dermatology associates, yardley, pa. objective: evaluate patient self-perceived av symptoms and impact of av on emotional/social functioning and adl, among pediatric patients with av in community practices across the u.s. methods: single-arm, prospective cohort study (proses) was conducted with moderate-tosevere non-nodular av patients >9yrs who were prescribed sarecycline in real-world u.s community practices. validated asis questionnaire (with signs and impact (emotional & social) domains) and an expert panel questionnaire (epq; emotional functioning (items 1-4), social functioning (items 5-7), and adl (items 8-11)) were completed by patients (>12yrs) and caregivers (for patients 9-11yrs) at baseline and week-12. all items were scored on five-point adjectival response scale (score: 0 (no burden/impact) – 4 (most burden/impact)); a higher asis domain score indicate severe symptoms or negative impact of av. asis domain scores and proportion of patients reporting score=2/3/4 (moderate to high burden/impact) for epq items at baseline for pediatric age strata (grp1: age 9-11yrs, grp2: age 12-17yrs) was analyzed. results: a total of 101 pediatric patients with av were included in the analysis. at baseline, patients reported moderate av burden in most domains, as depicted by signs domain scores of grp1: 2.00, grp2: 1.92; emotional impact subdomain scores of grp1: 2.00, grp2: 2.02; social impact subdomain scores of grp1: 1.13, grp2: 0.77. from epq items, proportion of patients reporting score=2/3/4 (moderate to severe burden) within age strata at baseline were: patients’ mood/anger (epq1)grp1: 25.00%, grp2: 41.24%; worries about av worsening (epq2)grp1: 50.00%, grp2: 74.23%; thinking about acne (epq3)grp1: 50.00%, grp2: 75.26%; level of acne worries (epq4)grp1: 50.00%, grp2: 64.95%; patients’ social media/’selfie’ activity (epq5)grp1: 50.00%, grp2: 37.11%; impact on real-life plans (epq6)grp1: 25.00%, grp2: 27.84%; efforts to hide av (epq7)grp1: 75.00%, grp2: 63.92%; picked-on/judged due to av (epq8)grp1: 25.00%, grp2: 26.80%; ability to reach future goals (epq9)grp1: 25.00%, grp2: 16.49%; parent understanding of av concerns (epq10)grp1: 75.00%, grp2: 82.47%; sleep impact (epq11)grp1: 50.00%, grp2: 20.62%. conclusion: moderate to severe av burden and psychosocial impact was observed in this prospective cohort of pediatric patients with av in the u.s. emotional impact and social impact of av were more pronounced across the pediatric age groups. synopsis conclusions • moderate to severe av burden and psychosocial impact was observed in this prospective cohort of pediatric patients with av in the u.s., at the beginning of proses study. • emotional impact and social impact of av were more pronounced across the pediatric age groups. methods • single-arm, prospective cohort study (proses: nct04820673) was conducted with moderate-to-severe non-nodular av patients ≥ 9yrs who were prescribed sarecycline in real-world u.s community practices. • a total of 300 subjects were enrolled from 30 community practices across the u.s. • validated asis questionnaire (with signs and impact (emotional & social) domains) and an expert panel questionnaire (epq; emotional functioning (items 1-4), social functioning (items 5-7), and adl (items 8-11)) were completed by patients (>12yrs) and caregivers (for patients 9-11yrs) at baseline and week-12. • asis items are scored on a five-point adjectival response scale (score 0-4); higher scores indicate severe symptoms or negative impact of acne. • epq items (1-9 & 11) were scored on five-point adjectival response scale (score: 0 (no burden/impact) – 4 (most burden/impact)); a higher epq score indicate severe symptoms or negative impact of av. • epq item 10 was scored on five-point adjectival response scale (score: 0 (not at all) – 4 (very much)); higher score indicate better understanding. • asis domain scores and proportion of patients reporting score=2/3/4 (moderate to high burden/impact) for individual epq items at baseline for pediatric age strata (grp1: age 9-11yrs, grp2: age 12-17yrs) were analyzed, as observed. objective • evaluate patient self-perceived av symptoms and impact of av on emotional/social functioning and adl, among pediatric patients with av in community practices across the u.s. majority of pediatric patients reported moderate to severe av burden in several areas associated with emotional and physical functioning, and adl, across the age groups note: survey responses for pediatric patients 9 11 years old (n=4), were from caregivers of these patients. survey responses for pediatric patients 12-17 years (n=97) were from patients themselves. moderate to severe (high) burden/impact refers to a score of 2/3/4 for the epq items, as follows: • epq1, ep3, epq5, epq6. epq7, epq8, epq11: some of the time (2), most of the time (3), all of the time (4) • epq2, epq4, epq9: somewhat (2), moderately (3), extremely (4) • epq10: somewhat (2), quite a bit (3), very much (4) results • 101 pediatric patients with data at week-12 were included in the final analyses. table 2: asis domain scores at baseline depicting moderate to severe av burden asis domain group 1: 9 11 years (n=4) group 2 12 – 17 years (n=97) signs 2.00 1.92 impact 1.78 1.70 emotional impact 2.00 2.02 social impact 1.13 0.77 results table 1: pediatric patient demographics demographic group n=101 age, mean years 14.84 gender, % male 49.17 female 50.86 race, % white 79.31 other 11.21 black / african american 6.90 asian 5.17 prefer not to answer 3.45 native hawaiian / pacific islander 1.72 american indian / alaskan 1.72 hispanic, latino, or of spanish origin, % 31.03 academic accomplishments, % pre-k – 5th grade 3.45 6th grade – 8th grade 19.83 9th grade – 12th grade 73.26 high school diploma / degree / vocational school 2.59 freshmen in college 0.86 u.s region (home location), % northeast 2.97 midwest 24.75 west 11.88 south 60.40 acne symptoms and impact of acne on social functioning, emotional functioning, and activities of daily living (adl) among pediatric patients with moderate to severe non-nodular acne vulgaris (av) in community practices across the u.s: a proses study analysis 25.00% 41.24% 0.0% 100.0% moderate/severe burden p ro po rt io n of p at ie nt s epq1: over the past 7 days, how often has your acne made you feel angry (mad/sad)? 9-11 yrs 12-17 years 50.00% 74.23% 0.0% 100.0% moderate/severe burden p ro po rt io n of p at ie nt s epq2: how worried are you about how long your acne will last and how bad it will get? 9-11 yrs 12-17 yrs 50.00% 75.26% 0.0% 100.0% moderate/severe burden p ro po rt io n of p at ie nt s epq3: how often do you think about your acne? 9-11 yrs 12-17 yrs 50.00% 64.95% 0.0% 100.0% moderate/severe burden p ro po rt io n of p at ie nt s epq4: over the past 7 days, how worried have you been about your acne? 9-11 yrs 12-17 yrs epq domain: emotional functioning 50.00% 37.11% 0.0% 100.0% moderate/severe burden p ro po rt io n of p at ie nt s epq5: how often do you change, edit, or filter your social media photo or selfie because of your acne? 9-11 yrs 12-17 yrs 25.00% 27.84% 0.0% 100.0% moderate/severe burden p ro po rt io n of p at ie nt s epq6: how often does acne impact your “in real life” plans? 9-11 yrs 12-17 yrs 75.00% 63.92% 0.0% 100.0% moderate/severe burden p ro po rt io n of p at ie nt s epq7: how often are you doing something to hide your acne? 9-11 yrs 12-17 yrs epq domain: social functioning 25.00% 26.80% 0.0% 100.0% moderate/severe burden p ro po rt io n of p at ie nt s epq8: how often do you feel picked on or judged because of your acne 9-11 yrs 12-17 yrs 25.00% 16.49% 0.0% 100.0% moderate/severe burden p ro po rt io n of p at ie nt s epq9: how concerned are you that your acne will affect your ability to reach your future goals (in school or work) and be the best you can be? 9-11 yrs 12-17 yrs 75.00% 82.47% 0.0% 100.0% moderate/high burden p ro po rt io n of p at ie nt s epq10: do you feel that your parents understand your acne-related concerns? 9-11 yrs 12-17 yrs 50.00% 20.62% 0.0% 100.0% moderate/severe burden p ro po rt io n of p at ie nt s epq11: over the past 7 days, how often has worrying about or discomfort (itching/hurting) from acne affected your sleep? 9-11 yrs 12-17 yrs epq domain: activities of daily living references 1. zuberbier t, et al. allergy. 2014;69:868–87; 2. saini s, et al. j invest dermatol. 2015;135:67–75; 3. maurer m, et al. n engl j med. 2013;368:924–35; 4. kaplan a, et al. j allergy clin immunol. 2013;132:101–9; 5. mathias sd, et al. ann allergy asthma immunol. 2010;105:42–8; 6. bretz f, et al. stat med. 2009;28:586–604. acknowledgments all authors participated in the development of the poster and approved the final poster for presentation. medical writing in the development of this poster was provided by novartis ireland ltd. editorial assistance was provided by jessica donaldson of fishawack communications ltd, oxford, uk. this poster was previously presented at the american academy of dermatology annual meeting, march 3–7, 2017, orlando, fl, usa, and at the 5th annual maui derm np+pa summer meeting, june 14–17, 2017, colorado springs, co, usa. funding this study was funded by novartis pharmaceuticals, east hanover, nj, usa. disclosures mh, h-sp, ai, y-my, t-bk, ay, jr, j-hl, and af have nothing to disclose. sk is an employee of novartis pharmaceuticals corporation. introduction • chronic idiopathic/spontaneous urticaria (ciu/csu) is a prevalent skin condition, characterized by the spontaneous appearance of wheals (hives) or angioedema, or both, that persist for ≥6 weeks1 • for patients who do not respond to h 1 antihistamines (h1ah) – the mainstay of treatment for ciu/csu1 – the humanized monoclonal anti-ige antibody omalizumab has been demonstrated to be an effective treatment option2–4 • three placebo-controlled, randomized phase 3 studies (asteria i [nct01287117], asteria ii [nct01292473], and glacial [nct01264939]) have established the efficacy and safety of omalizumab in a predominately caucasian population2–4 study outcome measures • the primary outcome was change from baseline in iss7. the primary analysis time point was at week 12 • secondary outcomes evaluated at week 12 were the following: − change from baseline in uas7 − change from baseline in hss7 − change from baseline in the dlqi score − percentage of iss7 mid responders − proportion of patients achieving uas7 ≤6 or uas7 =0 • safety was assessed through the summary of adverse events (aes) statistical analysis • a linear mixed model with repeated measures (country stratum, treatment group, week, and treatment-by-week interaction included as fixed effects, patient as a random effect, and baseline score as a covariate) was used to estimate treatment differences for the primary variable and selected secondary variables, including change from baseline to week 12 in uas7 and hss7 • treatment comparisons for proportions of patients at week 12 with iss7 mid response, uas7 ≤6, and uas7 =0 were performed using a logistic regression model (country stratum and treatment group as factors, and baseline value as a covariate) • a gate-keeping procedure was used to adjust the p-values of the two comparisons.6 the graphic approach of sequentially rejective, multiple testing procedures was used to illustrate the testing strategy of the two families of hypotheses6 results baseline characteristics • most disease characteristics were well balanced across treatment arms (table 1) − a slight imbalance in duration of ciu/csu was observed objective • the objective of the polaris study was to evaluate the efficacy and safety of omalizumab in an eastern asian population with ciu/csu who remain symptomatic despite h1ah therapy methods study design • polaris was a 26-week, randomized, double-blind, placebo-controlled, parallel-group multicenter phase 3 study, conducted in 41 sites (26 centers in japan and 15 in korea) • the study comprised a 2-week screening period, 12-week randomizedtreatment period, and 12-week follow-up (conducted between december 2014 and december 2015) (figure 1) • patients were randomized (1:1:1) to omalizumab 150 mg, 300 mg or placebo, administered subcutaneously every 4 weeks for a total of three doses conclusions • polaris represents the first phase 3, multicenter, randomized, double-blind, placebo-controlled clinical trial of omalizumab for ciu/csu in an eastern asian population • the results demonstrate that omalizumab treatment results in significant clinical benefits with no new safety concerns in patients with h1ah-refractory ciu/csu in japan and korea • these findings suggest that ethnic differences do not affect ciu/csu treatment outcomes with omalizumab screening (2 weeks) −2 baselineweek omalizumab or placebo 4 8 12 16 20 24 treatment (12 weeks) follow-up (12 weeks) screening primary analysis time point completed treatment completed study omalizumab 300 mg (n=73) omalizumab 150 mg (n=71) placebo (n=74) background treatment, h1ah (approved dose) +diphenhydramine* as needed additional h1ah (optional) figure 1. polaris study design *up to 80 mg/day (10 mg tablet in japan) or 75 mg/day (25 mg tablet in korea). h1ah, h 1 antihistamines. 100 90 80 70 60 50 40 30 20 10 0 p ro p o rt io n o f p a ti e n ts ( % ) oma 300 mg 87.7 oma 150 mg 68.6 placebo 55.4 1.84 (0.92, 3.69); p=ns* 5.51 (2.36, 12.86); p<0.001 figure 5. proportion of patients with iss7 mid response at week 12 data for odds ratio (95% ci) are presented. iss7 mid response defined as reduction from baseline in iss7 ≥5 points.5 p-values are unadjusted and represent differences between the indicated active treatment groups and placebo. *adjusted p-value was not <0.05. iss7, itch severity score over 7 days; mid, minimally important difference; ns, non significant; oma, omalizumab. m e a n c h a n g e f ro m b a s e li n e omalizumab or placebo administered * 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 (week) 0 −5 −10 −15 −20 −25 omalizumab 300 mg omalizumab 150 mg placebo figure 3. change from baseline in uas7 *ls mean values for change from baseline to week 12 in uas7 were –22.44, –18.79, and –13.90 with omalizumab 300 mg, 150 mg, and placebo, respectively. ls mean difference for treatment (95% ci): −8.55 (−12.05, −5.05), unadjusted p<0.001 (adjusted p<0.05) and −4.89 (−8.45, −1.34), unadjusted p=0.007 (adjusted p<0.05) for omalizumab 300 mg and 150 mg groups versus placebo, respectively. uas7 was defined according to previous studies for omalizumab.5 ci, confidence interval; ls, least squares; uas7, urticaria activity score over 7 days. 70 60 50 40 30 20 10 0 p ro p o rt io n o f p a ti e n ts ( % ) week 4 week 8 week 12 p<0.001 p=0.002 omalizumab 300 mg omalizumab 150 mg placebo proportion achieving uas7 ≤6 40 35 30 25 20 15 10 5 0 p ro p o rt io n o f p a ti e n ts ( % ) week 4 week 8 week 12 p<0.001 p=0.013* proportion achieving uas7 =0 omalizumab 300 mg omalizumab 150 mg placebo figure 6. proportion of responders by week 12 p-values are unadjusted and represent differences between the indicated active treatment groups and placebo. *adjusted p-value was not <0.05. uas7, urticaria activity score over 7 days. 100 90 80 70 60 50 40 30 20 10 0 c u m u la ti ve p ro p o rt io n o f p a ti e n ts w it h o u t e ve n t (% ) week 0 week 4 week 8 week 12 censor flags omalizumab 300 mg omalizumab 150 mg placebo survival curves omalizumab 300 mg omalizumab 150 mg placebo study week figure 7. time to uas7 ≤6 response uas7, urticaria activity score over 7 days. • patients treated with omalizumab experienced greater mean decreases in uas7 at all time points from week 1 through week 12, compared with patients in the placebo group (figure 3) − ls mean difference for omalizumab 300 mg and omalizumab 150 mg were p<0.001 and p=0.007 versus placebo, respectively • during posttreatment follow-up, mean uas7 values were increased in the omalizumab groups but did not revert to pretreatment levels (figure 3) • at week 12, a statistically significant improvement in hss7 was observed in both omalizumab groups compared with placebo (figure 4) • a statistically significant improvement was also observed in the overall dlqi score in the omalizumab 300 mg group compared with placebo (p<0.001) (figure 4) − the improvement in dlqi score observed with omalizumab 150 mg did not achieve statistical significance (adjusted p-value >0.05) m e a n c h a n g e f ro m b a s e li n e omalizumab or placebo administered * 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 (week) 0 −2 −4 −6 −8 −10 −12 omalizumab 300 mg omalizumab 150 mg placebo figure 2. change from baseline in iss7 *change from baseline in iss7 was the primary outcome and week 12 was the primary analysis time point; iss7 ls mean values at week 12 were −10.22, −8.80, and −6.51 with omalizumab 300 mg, 150 mg, and placebo, respectively. ls mean difference for treatment (95% ci): −3.70 (−5.31, −2.10), unadjusted p<0.001 (adjusted p<0.05) and −2.29 (−3.92, −0.65), unadjusted p=0.006 (adjusted p<0.05) for omalizumab 300 mg and 150 mg groups versus placebo, respectively. ci, confidence interval; iss7, itch severity score over 7 days; ls, least squares. study population • the study population consisted of males and females, aged 12–75 years, with a diagnosis of ciu/csu for ≥6 months that was refractory to conventional h1ah at the time of randomization • eligible patients had: − itch and hives for ≥8 consecutive weeks at any time prior to enrollment despite current h1ah treatment during this time period − urticaria activity score over 7 days (uas7) ≥16 and itch component of uas7 (range: 0–21) ≥8 during 7 days prior to randomization (day 1) − in-clinic uas ≥4 on at least one of the screening visits (day −14, day −7, or day 1) − been on an approved dose of an h1ah for ciu/csu for ≥3 consecutive days immediately prior to the day −14 screening visit and must have documented current use on the day of the initial screening visit • subjects recorded a daily symptom diary, reporting number of hives and intensity of pruritus (scale 0 [none] to 3 [intense/severe]) • average daily scores were totaled each week to provide itch severity score over 7 days (iss7; scale 0–21), number of hives score over 7 days (hss7; scale 0–21), and weekly composite outcome (uas7; scale 0–42). iss7 minimally important difference (mid) response defined as reduction from baseline in iss7 ≥5 points.5 the dermatology life quality index (dlqi) assessment was completed (scale 0–30), where lower scores represent better quality of life efficacy primary outcome • compared with baseline, mean iss7 was decreased and remained below baseline in all treatment groups during the 24-week study period (figure 2) − greater iss7 change from baseline was observed in the omalizumab 300 mg group versus omalizumab 150 mg from weeks 4 to 12, and was sustained up to week 20 in the follow-up • patients treated with omalizumab experienced greater mean decreases in iss7 at all time points from week 1 through week 12, compared with patients in the placebo group (figure 2) − least squares (ls) mean difference for omalizumab 300 mg and omalizumab 150 mg were p<0.001 and p=0.006 versus placebo, respectively • during post-treatment follow-up, mean iss7 values were increased in the omalizumab groups but did not revert to pretreatment levels (figure 2) secondary outcomes • compared with baseline, mean uas7 was decreased and remained below baseline in all treatment groups during the 24-week study period (figure 3) − greater uas7 change from baseline was observed in the omalizumab 300 mg group versus omalizumab 150 mg from weeks 4 to 12, and was sustained up to week 20 in the follow-up • at week 12, in the omalizumab 300 mg group the proportion of patients with iss7 mid response was significantly greater compared with placebo (figure 5) − results for omalizumab 150 mg were not significantly different compared with placebo 0 –2 –4 –6 –8 –10 –12 –14 c h a n g e f ro m b a s e li n e –2.63 (–4.75, –0.50)† oma 300 mg oma 150 mg placebo –12.17 –10.04 –7.41 –4.76 (–6.84, –2.67)* –1.9 (–3.36, –0.44)†,‡ –3.1 (–4.59, –1.69)* 0 –2 –4 –6 –8 –10 c h a n g e f ro m b a s e li n e oma 300 mg oma 150 mg placebo –8.4 –7.2 –5.3 change from baseline in hss7 change from baseline in overall dlqi score figure 4. efficacy outcomes at week 12 data for ls mean treatment difference (95% ci) are presented. *unadjusted p<0.001; †unadjusted p<0.05; ‡adjusted p-value was not <0.05. ci, confidence interval; dlqi, dermatology life quality index; ls, least squares; oma, omalizumab. table 1. demographics and baseline characteristics omalizumab 300 mg (n=73) omalizumab 150 mg (n=71)* placebo (n=74) age, years 44.6 (14.9) 43.6 (12.2) 42.5 (14.3) age group <18 years, n (%) 2 (2.7) 1 (1.4) 1 (1.4) female, n (%) 40 (54.8) 43 (60.6) 48 (64.9) ethnicity, n (%) japanese 35 (47.9) 34 (47.9) 36 (48.6) korean 38 (52.1) 37 (52.1) 38 (51.4) weight, kg 65.3 (13.3) 65.0 (14.1) 63.0 (13.4) body mass index, kg/m2 24.4 (3.9) 24.3 (4.8) 23.3 (4.0) duration of ciu/csu, years 3.6 (4.0) 5.1 (6.2) 4.7 (6.2) previous number of ciu/csu medications 6.8 (5.2) 6.3 (5.0) 7.4 (5.3) uas7 31.8 (7.1) 29.6 (7.4) 30.1 (6.5) iss7 14.6 (3.7) 13.2 (4.0) 13.7 (3.3) overall dlqi score 12.0 (6.5) 11.0 (5.9) 10.9 (6.4) data are mean (sd) for the randomized set, unless otherwise indicated. *one subject randomized to omalizumab 150 mg had uas7 and iss7 of 4.0 and 2.5, respectively. this patient did not meet the inclusion criterion and was excluded from the fas. ciu/csu, chronic idiopathic/spontaneous urticaria; dlqi, dermatology life quality index; fas, full analysis set; iss7, itch severity score over 7 days; uas7, urticaria activity score over 7 days; sd, standard deviation. table 2. treatment-emergent aes during the 24-week study period adverse events omalizumab 300 mg (n=73) omalizumab 150 mg (n=70) placebo (n=74) any ae 40 (54.8) 41 (57.7) 41 (55.4) any ae leading to discontinuation of study drug 0 1* (1.4) 0 any serious ae 3 (4.1) 3 (4.2) 0 death 0 0 0 any ae possibly related to study drug 7 (9.6) 6 (8.5) 9 (12.2) any severe ae 1 (1.4) 0 0 most frequent aes occurring in ≥2% of subjects nasopharyngitis 9 (12.3) 7 (9.9) 12 (16.2) eczema 5 (6.8) 3 (4.2) 2 (2.7) ciu/csu 3 (4.1) 1 (1.4) 1 (1.4) headache 3 (4.1) 3 (4.2) 5 (6.8) pharyngitis 3 (4.1) 3 (4.2) 0 data for the safety set are presented as number of patients (%). *any ae leading to discontinuation of study drug was reported in the omalizumab 150 mg group: pharyngeal edema (day 1 – day 4); suspected; mild. this ae was adjudicated as nonanaphylaxis by arc because it did not meet sampson criteria (ie, only one organ system involved). ae, adverse event; arc, adjudication review committee; ciu/csu, chronic idiopathic/spontaneous urticaria. safety and tolerability • overall incidence of aes was similar across treatment arms (54.8%, 57.7%, and 55.4% of subjects with omalizumab 300 mg, 150 mg, and placebo, respectively) (table 2) − nasopharyngitis was the most frequently reported ae with all treatments − ciu/csu events reported in the omalizumab 300 mg arm were reported in the follow-up epoch and were not deemed to be related to study medication − no exacerbation of ciu/csu, as indicated by uas7 response, was observed relative to baseline • at week 4, a higher proportion of responders (ie, achieving uas7 ≤6 or =0) was observed in the omalizumab 300 mg and 150 mg groups, compared with placebo (figure 6) • the difference in the proportions of responders in the active treatment and placebo groups was increased at the later assessments and were greater with omalizumab 300 mg than with omalizumab 150 mg (figure 6) • the median time to achieve uas7 ≤6 response was (figure 7): − 7 weeks in the omalizumab 300 mg group − 9 weeks in the omalizumab 150 mg group scan this qr code visit the web at: http://novartis.medicalcongressposters.com/default.aspx?doc=8b028 mobile friendly e-prints 3 ways to instantly download an electronic copy of this poster to your mobile device or e-mail a copy to your computer or tablet text message (sms) text: q8b028 to: 8nova (86682) us only +18324604729 north, central and south americas; caribbean; china +447860024038 uk, europe & russia +46737494608 sweden, europe standard data or message rates may apply. efficacy and safety of omalizumab in japanese and korean patients with chronic idiopathic/spontaneous urticaria (ciu/csu): results from the phase 3 polaris study michihiro hide,1 hae-sim park,2 atsuyuki igarashi,3 young-min ye,2 tae-bum kim,4 akiko yagami,5 jooyoung roh,6 jae-hyun lee,7 atsushi fukunaga,8 sam khalil,9 on behalf of the polaris study group 1department of dermatology, institute of biomedical and health sciences, hiroshima university, hiroshima, japan; 2department of allergy and clinical immunology, ajou university school of medicine, suwon, korea; 3department of dermatology, ntt medical center tokyo, tokyo, japan; 4department of allergy and clinical immunology, asan medical center, university of ulsan college of medicine, seoul, korea; 5department of allergology, fujita health university second educational hospital, nagoya, japan; 6department of dermatology, gachon university gil medical center, incheon, korea; 7department of internal medicine, institute of allergy, yonsei university college of medicine, seoul, korea; 8department of internal related, kobe university graduate school of medicine, kobe, japan; 9novartis pharma ag, basel, switzerland presented at the fall clinical dermatology conference, october 12–15, 2017, las vegas, nv, usa long-term follow up of ala 10% gel and red-light photodynamic therapy for the treatment of squamous cell carcinoma in situ we have previously demonstrated that aminolevulinic acid (ala) 10% gel with red-light pdt is safe and effective for the treatment of squamous cell carcinoma in situ (sccis) of the trunk and extremities.1 we performed a follow-up study in which nine of the original twelve patients in our pilot study returned 29 – 40 months after their last pdt treatment. all patients were clinically clear of disease and only one of seven patients biopsied had residual disease. our data supports that 10% ala gel with red-light pdt can achieve long-term clinical and histopathologic disease clearance and is a viable alternative to surgery for select sccis. synopsis • nine out of the original twelve patients in the pilot study returned for evaluation at least one year after their last pdt treatment • clinical assessment and possible punch biopsy were performed to evaluate clinical and histopathologic recurrence of sccis • cosmetic outcomes (rated 1-4) per the patient and investigator as well as patient satisfaction with pdt treatment were evaluated methods ala 10% gel with red-light pdt is effective to treat and induce long-term remission of sccis of the trunk and extremities. conclusion to determine the long-term efficacy of ala 10% gel with red-light pdt for the treatment of sccis of the trunk and extremities in immuno-competent patients. objective • all patients were clinically clear of disease • seven of the eight patients* who underwent a biopsy were clear of disease, indicating a long-term clearance rate of 88% • lesions that recurred were initially > 2 cm • cosmetic assessment evaluated by the patient was congruent with that of the investigator, which was good to excellent • seven out of nine patients were satisfied with pdt results 1. cervantes ja, zeitouni nc. photodynamic therapy utilizing 10% ala nano-emulsion gel and red-light for the treatment of squamous cell carcinoma in-situ on the trunk and extremities: pilot study and literature update. photodiagnosis photodyn ther. 2021;35:102358 * one of the patients that declined biopsy had a previous negative biopsy performed 6 months after last pdt long-term follow up of ala 10% gel and red-light photodynamic therapy for the treatment of squamous cell carcinoma in situ paul shim1, nathalie zeitouni md1, 2 1 university of arizona college of medicine, phoenix, arizona 2 medical dermatology specialists, phoenix, arizona this study was investigator-initiated and funded by biofrontera, inc. microsoft word 18. 670 proof done.docx skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 97 short communications secukinumab and latex allergies: don’t trust your emr y. david gu, bs,1 h. harris reynolds, md,2 rebecca kissel, md,2 boni e. elewski, md2 1vagelos college of physicians and surgeons, columbia university, new york, (ny) usa 2university of alabama at birmingham, department of dermatology, birmingham, (al) usa latex allergies are frequently encountered in the clinical setting and reactions can be observed following exposure to a variety of medical supplies.1 there have been relatively few reports of allergic reactions to injectable biologics, although the removable caps of autoinjectors and prefilled syringes often contain latex.1,2 herein, we report a systemic reaction in a latex-allergic psoriasis patient treated with secukinumab that highlights potential pitfalls in electronic prescription systems. a 24-year-old man was under our care for severe (pasi 13) plaque psoriasis. he was previously treated with several topical agents with no improvement, and the decision was made to begin systemic therapy with secukinumab. prior to starting therapy, we documented a history of latex allergy. he completed his loading dose of five injections over five weeks, with initial improvement of his psoriasis and no reported adverse effects. approximately 48 hours after the patient’s sixth injection, he developed an eczematous eruption over his face, trunk, and extremities. this was accompanied by bilateral periorbital and lower extremity edema. he denied any fevers, oral mucosal changes, wheezing, and dyspnea. the patient presented to our clinic three days following the onset of his symptoms, at which time he had mildly improved. physical examination revealed residual periorbital edema and diffusely distributed eczematous dermatitis overlying a background of post-inflammatory changes from previously treated psoriasis. additional investigation did not reveal any other precipitants that could account for his symptoms. secukinumab was discontinued and the patient was started on a short oral prednisone taper and antihistamines while transitioning him to an alternative biologic agent. his rash and swelling subsequently resolved without issue. our patient’s presentation had features consistent with a severe systemic allergic contact dermatitis and an immediate-type hypersensitivity. although difficult to definitively identify a cause, we believe this was due to the latex from the injection pen’s removable cap. the latency period observed in our case could be due to a variable amount of allergen that was leached from each cap, or sensitization to another allergen within the device or medication.3 to date, there have only been a few reported cases of similar allergic reactions to latex in patients treated with biologic agents.1,2 most importantly, while latex allergy is mentioned in secukinumab’s drug monograph, our electronic medical record skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 98 failed to flag it as a potential allergen. computerized decision support systems, which can alert physicians to potential medication-related adverse effects, have significantly improved patient safety.4,5 however, these systems may not always incorporate potential allergens that are specific to the route of administration. this may due to the to the separation between the bioactive drug and the delivery mechanism. as new therapies and delivery systems are developed, it is imperative that electronic medical systems are updated to reflect potential reactions resulting from the delivery system itself. furthermore, physicians cannot simply rely on decision support systems to identify potential safety issues. we must continue to stay abreast of newly developed therapies and have firm understanding of their potential adverse effects of both medications and delivery systems prior to prescribing. conflict of interest disclosures: dr. reynolds, mr. gu, and dr. kissel have no relevant conflicts of interest to declare. dr. elewski’s potential conflicts of interest are: clinical research supportresearch funding to university: abbvie, anaptysbio, boehringer, ingelheim, bristol myers squibb, celgene, incyte, leo, lilly, merck, menlo, novartis, pfizer, regeneron, sun, valeant (ortho dermatology), vanda; consultantreceived honorarium: boehringer ingelheim, celgene, leo, lilly, menlo, novartis, pfizer, sun, valeant (ortho dermatology), verrica funding: none corresponding author: hoyt harris reynolds md john n. whitaker building suite 3400 500 22nd street south birmingham, al 35233-3110 tel: 205.441.1364 e-mail: hharrisreynolds@gmail.com figure 1. periorbital edema and eczematous eruption 5 days after secukinumab injection references: 1. johnson c , zumwalt m, anderson n. latex hypersensitivity to injection devices for biologic therapies in psoriasis patients. cutis. 2018;102(2):116-118. 2. isabwe gac et al. hypersensitivity reactions to therapeutic monoclonal antibodies: phenotypes and endotypes. the journal of allergy and clinical immunology. 2018;142(1):159-170. https://doi.org/10.1016/j.jaci.2018.02.018 3. roest ma, shaw s, orton di. insulin-injection-site reactions associated with type i latex allergy. new england journal of medicine. 2003:348(3);265266. https://doi.org/10.1056/nejm200301163480320 4. dexheimer jw, kirkendall es, kouril m, et al. the effects of medication alerts on prescriber response in a pediatric hospital. appl clin inform. 2017;8(2):491–501. https://doi:10.4338/aci-201610-ra-0168 skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 99 5. eslami s, abu-hanna a, de keizer nf. evaluation of outpatient computerized physician medication order entry systems: a systematic review. j am med inform assoc. 2007;14(4):400–406. https://doi:10.1197/jamia.m2238 importance of complete skin clearance on quality of life: analysis of three phase 3 studies of brodalumab april armstrong,1 andrew blauvelt,2 scott drew,3 roger ho,4 abby jacobson5 1university of southern california, los angeles, ca; 2oregon medical research center, portland, or; 3ohiohealth, marion, oh; 4 the ronald o. perelman department of dermatology, new york university school of medicine, new york, ny; 5ortho dermatologics (a division of bausch health us, llc), bridgewater, nj 39th annual fall clinical dermatology conference® for dermatologists • october 17-20, 2019 • las vegas, nv introduction • complete skin clearance is an important treatment goal for patients with psoriasis1 • evidence shows that complete skin clearance is associated with several benefits over almost-clear skin, including improved quality of life1 • brodalumab is a human anti–interleukin-17 receptor a monoclonal antibody that is efficacious in treating moderate-to-severe psoriasis2-4 • in the phase 3 brodalumab trials amagine-1, -2, and -3, 42%, 44%, and 37% of patients receiving brodalumab 210 mg every 2 weeks (q2w), respectively, achieved a psoriasis area and severity index score of 100 (pasi 100) at week 122,3 objective • to explore whether patients with psoriasis achieving complete skin clearance experienced greater improvements in quality of life than those achieving a good but less-than-complete response methods • data for this post hoc analysis were pooled from the nonplacebo groups of the 12-week induction phases of three phase 3 clinical trials (amagine-1/-2/-3) of brodalumab in patients with moderate-to-severe plaque psoriasis • patients included in the analysis were treated with brodalumab (140 or 210 mg) or ustekinumab (45 or 90 mg) and had achieved complete skin clearance, defined as 100% improvement in pasi score (pasi 100), or good but incomplete skin clearance, defined as pasi 90 to <100 • patient-reported outcomes were used to evaluate quality of life (figure 1), stratified by complete or good but incomplete skin clearance results • at week 12, mean (standard deviation [sd]) hospital anxiety and depression scale anxiety and depression scores were numerically lower for patients achieving pasi 100 (anxiety, 4.75 [3.30]; depression, 2.90 [3.00]) than for patients achieving pasi 90 to <100 (anxiety, 5.09 [4.16]; depression, 3.55 [3.18]; figure 2) • numerically fewer work limitations, indicated by mean (sd) work limitations questionnaire scores, were reported by patients achieving pasi 100 (2.29 [3.11]) than by those achieving pasi 90 to <100 (3.00 [3.58]; figure 2) • at week 12, mean (sd) sf-36 mental component summary (mcs) and physical component summary (pcs) scores were similar among patients who achieved pasi 90 to <100 (mcs, 51.39 [7.68]; pcs, 52.53 [7.82]) and pasi 100 (mcs, 52.96 [7.99]; pcs, 52.38 [8.71]; figure 3) acknowledgments: this study was sponsored by ortho dermatologics. medical writing support was provided by medthink scicom and funded by ortho dermatologics. ortho dermatologics is a division of bausch health us, llc. references: 1. takeshita et al. j am acad dermatol. 2014;71:633-641. 2. siliq [package insert]. valeant pharmaceuticals north america llc; 2017. 3. lebwohl et al. n engl j med. 2015;373:1318-1328. 4. papp et al. br j dermatol. 2016;175:273-286. 5. allaire. arthritis rheum. 2003;49(suppl 5s): s85-s89. 6. grassi et al. value health. 2010;13:469-478. conclusions • achievement of complete skin clearance (pasi 100) was associated with greater numeric improvements in quality-of-life measures than achievement of a good but less-than-complete response in patients with moderate-to-severe plaque psoriasis • these results suggest that therapies likely to help patients achieve complete skin clearance, such as brodalumab, are important to consider when making treatment decisions © 2019. all rights reserved. sf-36 pcs scoresf-36 mcs score hads depression score wlq hads anxiety score figure 1. quality of life measures assessed in this post hoc analysis. mean wlq score mean hads depression score mean hads anxiety score 3.55 2.90 5.09 4.75 3.00 2.29 greater anxiety, depression, or work impairment less anxiety, depression, or work impairment complete skin clearance (pasi 100) good but incomplete response (pasi 90 to <100) figure 2. mean quality of life measure scores by categories of complete skin clearance (pasi 100) or good but incomplete response (pasi 90 to <100) at week 12. the hads is a 14-item questionnaire, with higher scores indicating worse anxiety or depression.4 the wlq measures on-the-job limitations due to health problems and health-related productivity loss, with higher scores indicating greater impairment.5 hads, hospital anxiety and depression scale; pasi, psoriasis area and severity index; wlq, work limitations questionnaire. 52.53 52.38 51.39 52.96 better health worse health mean sf-36 component score mcs score pcs score complete skin clearance (pasi 100) good but incomplete response (pasi 90 to <100) figure 3. mean mcs and pcs scores by categories of complete skin clearance (pasi 100) or good but incomplete response (pasi 90 to <100) at week 12. sf-36 scores include 8 health domains yielding the mcs and pcs scores, with higher scores indicating better health.6 mcs, mental component summary; pasi, psoriasis area and severity index; pcs, physical component summary; sf-36, short form 36 health survey. hads, hospital anxiety and depression scale; mcs, mental component summary; pcs, physical component summary; sf-36, short form 36 health survey; wlq, work limitations questionnaire. skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 570 original research association of single-nucleotide polymorphisms of gene xpc with susceptibility to basal cell carcinoma in brazilian population mayara dos santos maia2,5, otávio sérgio lopes3,4, poliane da silva calixto2,5, sylvia satomi takeno herrero2, augusto monteiro de souza2,5, carlos alberto longui4, ivan rodrigues de carvalho filho8, leonardo ferreira soares6, plínio delatorre1,2,5, renally barbosa da silva9, danielle calcagno7, rommel rodriguez burbano7, eleonidas moura lima1,2,5 1departamento de biologia molecular; universidade federal da paraíba; joão pessoa pb – brasil 2laboratório de biologia molecular estrutural e oncogenética lbmeo; universidade federal da paraíba; joão pessoa pb – brasil 3departamento de dermatologia; clinica dermatológica santa catarina; joão pessoa pb – brasil 4programa de pós-graduação em ciências da saúde; faculdade de ciências médicas da santa casa de são paulo; são paulo – sp – brasil 5programa de pós-graduação em biologia celular e molecular, universidade federal da paraíba; joão pessoa pb – brasil 6departamento de farmácia; universidade estadual da paraíba; campina grande pb – brasil 7instituto de ciências biológicas; universidade federal do pará; belém pa – brasil 8depatamento de patologia, laboratório de análises médicas unilab, joão pessoa pb – brasil 9programa de pós-graduação em ciências naturais e biotecnologia; universidade federal de campina grande – ufcg, campus de cuité – pb – brasil abstract background: basal cell carcinoma (bcc) is the common neoplasm in humans and its main etiological factor is exposure to solar radiation. mutations in repair genes can lead to tumor progression and loss of cell integrity leading to the onset of cancer. nucleotide excision repair (ner) is an important mechanism primarily used to repair injuries caused by uv. objective: to evaluate and describe for the first time the single nucleotide polymorphisms rs745769173, rs761106780 and rs535425175 and risk of developing bcc. methods: the present study analyzed 100 samples of paraffin-embedded tissue from patients with histopathological diagnosis of bcc and 100 control samples. the results were obtained by genotyping method, dideoxy unique allele specific – pcr (dsasp) and molecular modeling. results: the snp rs535425175 of the xpc gene showed a significant association with the bcc in the analyzed samples (p <0.005) and molecular docking showed different binding energy of the complex between the xpc region 99-156 and the ph domain of tfiih p62, being more negative, -710.53 kcal/mol, with the asn residue at position 108 and less negative, -611.10 kcal/mol, with lys residue related to the polymorphism. conclusion: the results suggest that the snp rs535425175 of the xpc gene, which causes mutation at codon 108 of the xpc protein, which consists of replacing the ans residue with the lys, may be considered a risk factor associated with the development of bcc. skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 571 basal cell carcinoma (bcc) is the most common neoplasia in the world and originates from pluripotent basal cells that have lost their differentiation capacity [1,2]. the main etiological factor is exposure to uvb rays that damage dna [3], which can lead to mutations in important genes regulating cellular functions [4]. other factors and personal genetic predispositions may also be associated with the development of bcc [5]. the cell has several pathways of repair mechanisms involving more than 130 genes that correct dna damage, contributing to the integrity and maintenance of genomic stability. however, mutations in repair genes can lead to tumor progression and loss of cell integrity leading to the onset of cancer [6]. nucleotide excision repair (ner) is an important mechanism for repairing uvinduced lesions and removing adducts that prevent replication and dna transcription. the ner pathway is composed of 28 genes, eight of which are from the xp family. defects in some of these genes may lead to the development of several syndromes, among them xeroderma pigmentosum (xp), which is associated with the deficiency of dna repair caused by uv radiation lesions [6,7]. the xpa gene is located in the chromosomal region 9q22.33 [8]. it is involved in both global and transcriptional genome repair pathways [9]. xpa detects the presence of dna damage, recruits ner factors, stabilizes repair intermediates, positions repair machinery in dna and interacts with various proteins, such as tfiih and ercc1-xpf, rpa, hhrd23b, ddb, pcna [10,11]. the xpc gene is located in the chromosomal region 3p25.1 [12]. xpc recognizes and binds to damaged dna, interacts with hhr23 to protect itself from proteolytic degradation, interacts with centn2 to increase its binding affinity for dna. it recruits the tfiih, which acts as a helicase and together with the rpa constitutes the pre-incision complex, opening the double helix [12-15]. several studies have investigated the influence of many snps on the xpa and xpc genes in the risk of developing cbc [16-20]. however, this study is pioneer in the analysis and description of snps of xpa (rs745769173) and xpc (rs535425175 and rs761106780) in samples from patients with bcc histopathological diagnosis in brazil. the first time being in the literature, that these snps are described and analyzed. samples the present study analyzed 100 samples of paraffin-embedded tissue from patients with histopathological diagnosis of bcc, totaling 200 alleles for each snp studied and 100 control samples obtained from paraffinembedded normal tissue from cancer-free patients from the laboratory of structural molecular biology and oncogenetic – labmeo/ ufpb sample bank. it is a retrospective study and samples has more than five years old and were provided by the bank of data by the laboratory unilab/joão pessoa – pb and labmeo/ ufpb sample bank. the present study is part of the thematic project approved by the ethics committee of the university hospital lauro wanderley ufpb under the code caae: 36522614.2.3001.5883. introduction methods skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 572 dna extraction the samples were submitted to dna extraction in laboratory of structural molecular biology and oncogenetic lbmeo/ ufpb. the dna sample was extracted according to the method described by shang rong-shi et al [21] with modifications. the isolated genomic dna was quantified with the spectrophotometer nanodrop™ 2000c from thermo fisher scientific and stored at -20ºc. method dideoxy single allele-specific pcr-dsasp the dsasp method is based on chainterminating inhibitors, dideoxynucleotide, established by the method of sanger et.al. dsasp was previously validated by the allele specific pcr-asp method as described by lima et al. [22]. the dsasp is a method of genotyping and comprises four stages: i selection of snps of interest, design of the oligonucleotides (primer and complementary sequence) and determination of the dideoxynucleotide to be incorporated; ii asymmetric pcr as dideoxynucleotide of interest; iii hybridization reaction between complementary sequence and asymmetric pcr product; iv analysis by melting curve by qpcr and was validated and developed by lima et al. [22]. to genotype the snps rs745769173 (xpa gene), rs761106780 and rs535425175 (xpc gene) by dsasp method, asymmetric pcr was performed for each snp of interest, complementary sequence and dideoxynucleotide incorporation. the oligonucleotides were obtained by in silico validation (generunner software). validation in silico the primers used for dsasp of the snps rs745769173 (xpa gene), rs761106780 and rs535425175 (xpc gene) were designed based on the database ensembl genome browser and using the gene runner program to evaluate the annealing temperature, the formation of secondary structure and size of the amplified fragments. asymmetric pcr conditions asymmetric pcr was performed in a final volume of 25 μl containing 200 μm dntp (datp, dctp, dttp and ddgtp), 2.0 mm mgcl2, 20 ng/μl dna, 200 pm primer and 0.5 u amplitaq gold (life technologies carlsbad, ca). pcr conditions for amplification of single stranded dna were as follows: a pre-denaturation for 3 min at 94°c and 80 cycles of 94°c for 20 s of 50°c for 45 s and 72°c for 30 s with a final extension of 5 min at 72°c. hybridization conditions the product of the pcr amplification of each sample was subjected to hybridization step under the following conditions: 200 pm of the complementary sequence at 4°c for 10 min. melting curve analysis the melting curve were analysed to determine the tm performed by real time pcr equipment 7500 fast real-time pcr system (life technologies carlsbad, ca) following the conditions: preheat starting at 25ºc to 95ºc for 1 min, folding up to 45ºc for 5 min and gradual heating (1°c/min) until a temperature of 95°c for 5 min. for melting curve analysis, sybr® green mix (life technologies carlsbad, ca) was used. molecular modeling skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 573 in the present work to construct the xpc region 99-156 the a chain of the complex between the xpc acid domain and the ph domain of tfiih p62 (pdb 2rvb) [23] was used, which was treated with the swiss-pdb viewer was added the residues thr 99, gln 100, asp 101, ile 102, pro 103, ser 104, asp 105, leu 106, lys 107 and asn 108 [24]. optimization and refinement of the structure was performed using wincoot 0.8.4 [25] and the galaxyrefine server (http://galaxy.seoklab.org/index.html) [26]. the local and global quality of the amino acids of the three-dimensional structure of the model was analyzed by prosa [27] and local quality by the qmean [28] force fields. the overall quality of the model was determined by the data generated by qmean6 [29]. docking for the docking tests using hex 8.0.0 software [30], two anchorages were generated, the first between xpc protein with asn residue at codon 108 and the ph domain of tfiih p62; and a second anchorage between the mutated xpc-modeled protein at position 108, substitution of asn with lys and the ph domain of tfiih p62. the mutation of xpc protein, in which substitution of asn by lys at position 108 was performed using the software wincoot 0.8.4 [25]. molecular docking was done using the ph domain of tfiih p62 (b-chain, residues 1-108) which was cut out of the structure resolved by nuclear magnetic resonance (nmr) and deposited in the protein data bank (pdb) code (2rvb) [23]. the binding energies of the complexes were obtained using hex 8.0.0 and for visualization of the complexes the pymol was used [32]. statistical analysis the allelic frequencies and genotypic distributions were obtained by the hardyweinberg equilibrium model. the association analysis was performed using chi-square and fisher's exact test, using the statistical program bioestat 5.3, where p <0.05 was considered significant. the snps rs745769173 of the xpa gene and the rs761106780 of the xpc gene were not associated with basal cell carcinoma. only rs535425175 of the xpc gene was shown to be associated with the development of bcc when compared to control samples (p <0.005) (table 2.). the genotypic distributions of rs535425175 was n = 6 c/c (lys/lys), n = 14 a/c (asn/lys) and n = 80 a/a (asn/ans). the observed t m was 70 °c for allele a and 87 °c for allele c (figures 1 and 2). our results also suggest that there was a statistical significance between the genotypes of the xpc gene rs535425175 and the gender (p = 0.0384), but for the other variables studied there was no significance: age (p = 0.7281), tumor location (p = 0.3792) and histological type (p = 0.6172) (table 3.). the modeling and validation of the threedimensional model for region 99-156 of the xpc protein was validated by the prosa method, which assigned a negative value of approximately -0.13, positioning the model, represented by the black point, within the dark gray area, to which indicates scores of other structures deposited in the pdb presenting the same size of the model of this research (figure 3). data from the comparison of the six qmean parameters for the proposed model for xpc region 99-156 with the scores of structures of the same size deposited in the pdb indicated results skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 574 figure 1. genotype a/a of the snp rs535425175 of the xpc gene with tm 70ºc for the allele a. skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 575 figure 2. the genotype a/c of the snp rs535425175 of the xpc gene with tm d87ºc for the c allele. skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 576 figure 3. structure of the complex between the xpc acidic string and the tfiih p62 ph domain. (a) domain organization of xpc acidic string (as) and and tfiih p62 (ph). (b) three-dimensional structure of the acidic string of xpc interacting with the ph domain of tfiih p62. skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 577 that the structure is satisfactory, since it revealed a qmean score of 0.75 and zscore of 0.12 (figure 4). thus, the xpc model (region 99-156) is considered a good model from the thermodynamic point of view and of structural quality, because it presents values close to proteins already elucidated experimentally. the molecular docking carried out showed that the binding energy of the complex between the xpc region 99-156 and the ph domain of tfiih p62 is more negative and equivalent to -710.53 kcal/mol compared to the docking between the xpc (99-156) with substitution polymorphism, asn 108 replaced by a lys, with the ph domain of tfiih p62, in which the energy of the complex is -611.10 kcal/mol. several single-nucleotide polymorphisms have been associated with susceptibility to the development of cancer. the snps investigated in this work (rs745769173 xpa, rs535425175 and rs761106780 xpc) is the first time they are described and evaluated in neoplastic tissue and were selected because they are close or in regions of interaction with other proteins. miller et. al analyzed several snps in the xpa gene, one in the utr region (rs1800975) and haplotypes within introns (rs3176633, rs3176689, rs2805835, rs3176719, rs1962592, rs3176751 and rs3176690) in patients with bcc and squamous cell carcinoma (scc). they found that the g allele of polymorphism rs1800975 is associated with an increased risk of bcc and scc and the seven haplotypes were in the hardy-weinberg equilibrium. this was the first study to relate polymorphisms in the xpa gene with the predisposition to the development of non-melanoma skin cancer [15]. differently from miller et al [15], ding et al performed a meta-analysis to analyze the association of rs1800975 polymorphism with cancer risk. they verified that of the 36 control cases analyzed, in general there was no significant association between the polymorphism and the susceptibility to develop cancer. however, in stratified analysis by type of cancer, it was observed that individuals with variant genotypes present a higher risk of lung cancer [32]. significant associations were also found between the rs2228001 polymorphism (xpc) and the risk of lung cancer in the asian population. jin et al in the meta-analysis conducted on the basis of 14 studies found that the homozygous genotype lys939gln was associated with the risk of developing lung cancer. while the polymorphism rs2228000 was not associated with the risk of this pathogenesis [33]. in squamous cell carcinoma of the head and neck (ccecp), a type of non-melanoma skin cancer, farnebo et. al sought to investigate pns as potential risk factors and indicators of survival among caucasian patients. four polymorphisms of four genes of the nucleotide excision repair mechanism were studied in 169 patients and 344 controls. the results suggest that all snps may affect the risk and survival of ccecp and that rs222800 (xpc) is associated with an increased risk of ccecp and laryngeal carcinoma. statistical analyzes also revealed a twofold increased risk in patients diagnosed with ccecp in the presence of the t allele in the total group, as well as in homozygous men p = 0.02 and a three-fold increased risk in laryngeal carcinoma [34]. discussion skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 578 no association studies of xpc gene snp with susceptibility to the development of basal cell carcinoma were found. but there are some studies of association of polymorphisms with the risk of developing melanoma. zhou et al performed metaanalyzes on the association of lys939gln polymorphism in the pathogenesis of melanoma in caucasians, but the results suggest that there was no evidence of an important role of this polymorphism [35]. our results suggest that there is no association between rs745769173 and rs761106780 of the xpa and xpc genes, respectively, with susceptibility to the development of bcc. however, it was a significant association (p<0.005) between polymorphism rs535425175 (xpc) and susceptibility to the development of bcc. the rs535425175 is a snp near the codon downstream of the site of interaction with tfiih, a helicase recruited by the xpc required repair activity. the analysis revealed that the homozygous genotype c/c confers an increased risk of developing bcc. although residue 108 of the xpc protein did not participate in the ph domain interaction of tfiih p62 in any of the complexes. however, energy values suggest that the occurrence of complex binding between xpc (99-156) with the asn residues and the ph domain of tfiih p62 is more favorable, 710.53 kcal/mol, compared to the domain binding of xpc (99-156) with the lys residues and the ph domain of tfiih p62, 611.10 kcal/mol. thus, the results obtained by docking suggest that the complex proteinprotein interaction formed with lys residue at codon 108 reflects snp rs535425175, which contributes to complex instability, corroborating the association of snp rs535425175 to the susceptibility to the development of basal cell cancer by genetic analysis. the results suggest that the mutation at codon 108 of the xpc protein, which consists of replacing the ans residue with the lys residue related to the snp rs535425175 is a risk factor and a potential molecular marker for susceptibility to the development of bcc. as the snp rs535425175 was the first time described the need for more studies to corroborate its importance. conflict of interest disclosures: none funding: this work was supported by grants of capes, cnpq and clinica dermatológica santa catarina; joão pessoa pb – brasil. acknowledgements: the authors would like to thank jimmy johnson for proofreading the article. corresponding author: eleonidas moura lima phone: +55 (83) 321674 email: eleonidas@pq.cnpq.br references: 1. otsuka a, levesque mp, dummer r, et al (2015) hedgehog signaling in basal cell carcinoma. japanese society for investigative dermatology. doi:10.1016/j.jdermsci.2015.02.007. 2. jorgensen t. j, et al (2012) a populationbased study of hedgehog pathway gene variants in relation to the dual risk of basal cell carcinoma plus another câncer. cancer epidemiol. doi:10.1016/j.canep.2012.05.001. 3. dourmishev la; rusinova d, botev i (2013) clinical variants, stages, and management of basal cell carcinoma. indian dermatology online journal. doi:10.4103/22295178.105456. 4. scott ga, laughlin ts, rothberg pg (2014) mutations of the tert promoter are common in basal cell carcinoma and squamous cell carcinoma. modern pathology. doi:10.1038/modpathol.2013.167. 5. kosiniak-kamysz a, pośpiech e, wojas-pelc a, et al (2012) potential association of single nucleotide polymorphisms in pigmentation genes with the development of basal cell conclusion skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 579 carcinoma. journal of dermatology. doi:10.1111/j.1346-8138.2012.01559.x. 6. decordier i, loock kv, lirsch-volders m (2010). phenotyping for dna repair capacity. mutation research. doi:10.1016/j.mrrev.2010.05.002. 7. nemzow1 l, lubin a, zhang l, gong f. xpc: going where no dna damage sensor has gone before. dna repair (amst). 2015. doi:10.1016/j.dnarep.2015.09.004. 8. tanaka k, miura n, satokata i, et al (1990) analysis of human dna excision repair gene involved in group a xeroderma pigmentosum and containing a zinc-finger domain. nature. doi:10.1038/348073a0. 9. ding d, zhang y, yu h, et al (2012) genetic variation of xpa gene and risk of cancer: a systematic review and pooled analysis. international journal of cancer. doi:10.1002/ijc.26391. 10. scharer od (2013) nucleotide excision repair in eukaryotes. cold spring harbor perspectives in biology. doi:10.1101/cshperspect.a012609. 11. nishi r, okuda y, watanabe e, et al (2005) centrin 2 stimulates nucleotide excision repair by interacting with xeroderma pigmentosum group c protein. molecular and cellular biology. doi:10.1128/mcb.25.13.5664-5674.2005. 12. kamionka m, feigon j (2004) structure of the xpc binding domain of hhr23a reveals hydrophobic patches for protein interaction. protein sci. doi:10.1110/ps.04824304. 13. sugasawa, k (2016) molecular mechanisms of dna damage recognition for mammalian nucleotide excision repair. dna repair. doi:10.1016/j.dnarep.2016.05.015. 14. francisco g, menezes pr, chammas r (2008) xpc polymorphisms play a role in tissue-specific carcinogenesis: a metaanalysis. european journal of human genetics. doi:10.1038/ejhg.2008.6. 15. brambullo t, colonna mr, vindigni v,1 piaserico s, et al (2022). xeroderma pigmentosum: a genetic condition skin cancer correlated—a systematic review. biomed research international. doi.org/10.1155/2022/8549532. 16. miller kl, karagas mr, kraft p, et al (2006) xpa, haplotypes, and risk of basal and squamous cell carcinoma. carcinogenesis. doi:10.1093/carcin/bgi376. 17. mei c, hou m, guo s, et al (2013) polymorphisms in dna repair genes of xrcc1, xpa, xpc, xpd and associations with lung cancer risk in chinese people. thoracic cancer. doi:10.1111/17597714.12073. 18. sakoda lc, loomis mm, doherty ja, et al (2012) germ line variation in nucleotide excision repair genes and lung cancer risk in smokers. int j mol epidemiol genet 3:1-17. 19. he l, deng t, hesheng l (2015) xpa a23g polymorphism and risk of digestive system cancers: a meta-analysis. onco targets and therapy 8:385–94. 20. lin y, chahal hs, wu1 w, cho hg, et al (2017). association study of genetic variation in dna repair pathway genes and risk of basal cell carcinoma int j cancer. doi:10.1002/ijc.30786. 21. shang-rong s, cotel, rj, wu l, et al (2002) dna extraction from archival formalin-fixed, paraffin-embedded tissue section based on the antigen retrieval principle: heating under the influence of ph. the journal of histochemestry e cytochemestry. thousand oaks ca 50:1005-11. 22. lima em, lopes os, soares lf; et al (2015) dideoxy single allele-specific pcr dsasp new method to discrimination allelic. braz arch biol technol 58:414-20. 23. okuda m, kinoshita m, kakumu e, et al (2015) structural insight into the mechanism of tfiih recognition by the acidic string of the nucleotide excision repair factor xpc. structure 23:1827-37. 24. guex n, peitsch mc (1997) swiss‐model and the swiss‐pdb viewer: an environment for comparative protein modeling. electrophoresis. doi:10.1002/elps.1150181505. 25. emsley p, cowtan k (2004) coot: modelbuilding tools for molecular graphics. acta crystallographica section d: biological crystallography. doi:10.1107/s0907444904019158. 26. ko j, park h, heo l, et al (2012) galaxyweb server for protein structure prediction and refinement. nucleic acids 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protein crystallography 40:82-92. 32. ding d, zhang y, yu h, et al (2012) genetic variation of xpa gene and risk of cancer: a systematic review and pooled analysis. international journal of cancer. doi:10.1002/ijc.26391. 33. jin b, dong y, zhang x, et al (2014) association of xpc polymorphisms and lung cancer risk: a meta-analysis. plos one. doi:10.1371/journal.pone.0093937. 34. farnebo l, stjernström a, fredrikson m, et al (2015) dna repair genes xpc, xpd, xrcc1, and xrcc3 are associated with risk and survival of squamous cell carcinoma of the head and neck. dna repair. doi:10.1016/j.dnarep.2015.05.003. 35. zhou l, lu y, yang g, et al (2014) quantitative assessment of the association between xpc lys939gln polymorphism and cutaneous melanoma risk. tumor biol. doi:10.1007/s13277-013-1196-y powerpoint presentation pilot study assessing the efficacy of a novel topical adhesive for dermatologic excisional wound closure ryan m. svoboda, md ms1, joshua d. zuckerman, md2, darrell s. rigel, md ms3* background objective methods results limitations conclusions 1national society for cutaneous medicine, new york, ny 2schweiger dermatology, new york, ny 3ronald o. perelman dept. of dermatology, nyu medical center, new york, ny • the topical adhesive, 2-octyl cyanoacrylate, has been used as an alternative to suture or staple closure of the skin in a variety of procedures • while the use of adhesive carries potential benefits in terms of ease of application, prior reports of allergic contact dermatitis and burns from exothermic reactions have presented a potential barrier to usage • to investigate the feasibility of using a novel formulation of 2-octyl cyanoacrylate (actabond-bergen medical products, inc., morris plains, nj) for skin closure after surgical excision of cutaneous lesions *1 patient lost to follow-up **< 1mm skin edge separation, treated conservatively • the results of office-based cutaneous surgical excisions using a novel formulation of 2-octyl cyanoacrylate for skin closure were examined in 9 consecutive patients (10 lesions) • surgical sites were photographed: • pre-operatively • intraoperatively (open wound, prior to adhesive application, following adhesive application) • two-weeks post-operatively • at follow-up, patient satisfaction was assessed and all incisions were examined for: • cosmetic result • signs of infection • small sample size in this pilot series • no comparison group • one patient treated with adhesive was lost to followup • a novel formulation of 2-octyl cyanoacrylate appears to be a feasible alternative to the use of sutures for skin closure following in-office dermatologic excision • although allergic exothermic reactions were of concern with prior formulations of 2-octyl cyanoacrylate, none were noted in this pilot series • larger studies are needed to determine potential advantages of this closure method *disclosures: this study was financially supported in part by a grant from bergen medical products, inc. skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 719 brief article linear depigmented macules and patches in elderly man maansi kulkarni, ba1, clayton conner, md2, sean igelman, md2, julian trevino, md2 1 boonshoft school of medicine, wright state university, dayton, oh 2 department of dermatology, boonshoft school of medicine, wright state university, dayton, oh pd-1 inhibitors have been associated with several dermatologic conditions including various dermatitides and vitiligo, as well as more serious conditions such as drug hypersensitivity syndrome, stevens-johnson syndrome, and toxic epidermal necrolysis.1,2 vitiligo is not an uncommon adverse dermatologic condition in the setting of immune checkpoint inhibitor use. one study showed that ipilimumab-induced vitiligo was seen in 11% of metastatic melanoma patients.3 in fact, vitiligo has the highest level of evidence for association with all checkpoint inhibitor therapy. segmental vitiligo, that is depigmentation in a blaschkoid distribution that detail embryonic cell migration, has yet to be reported with pd-1 checkpoint inhibitors. an 82-year-old african american male with a history of small cell lung cancer presented with new onset spreading depigmented macules and patches. at the time of presentation, the patient had received six months of a chemotherapy regimen consisting of taxol, carboplatin, and durvalumab. the patient stated that he first noticed pink pruritic macules on the right dorsal forearm within weeks of starting chemotherapy. within the next several months, these macules evolved into depigmented macules and patches. a similar small group of macules later appeared on the contralateral posterior neck. the patient was extremely bothered by the appearance of his condition and attempted to treat it with overthe-counter hydrocortisone cream without success. the patient denied use of other medications as well as personal or family history of any autoimmune conditions. abstract the development of immune checkpoint inhibitors such as programmed cell-death receptor 1 (pd-1) antagonists has rapidly advanced chemotherapy within the last several decades. pd-1 targeted immunotherapy drugs like pembrolizumab, ipilimumab, nivolumab, and durvalumab have known associations with several immune-mediated dermatological reactions. we report a case in which an elderly male experienced segmental vitiligo after use of durvalumab therapy for small cell lung cancer. distinct from non-segmental vitiligo, segmental vitiligo presents in a unilateral blaschkoid distribution and typically does not cross the midline. to our knowledge, checkpoint inhibitor-induced segmental vitiligo has yet to be documented. introduction case report skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 720 physical examination revealed a linear distribution of depigmented macules coalescing into patches on the proximal posterior right upper arm with distal extension curving anteriorly towards the right dorsal forearm (figure 1). an additional linear grouping of four small, depigmented macules was present on the left posterior neck immediately adjacent to midline (figure 2). all depigmented macules demonstrated accentuation with wood’s lamp examination. figure 1. blaschkoid distribution of depigmentation is observed on the proximal posterior right upper arm with distal extension curving anteriorly towards the right forearm. a 4 mm punch biopsy of the right upper arm revealed basal vacuolization, apoptotic keratinocytes, and numerous pigment-laden macrophages. areas of epidermis lacked pigmentation. a fontana-masson stain confirmed dermal melanophages as well as the absence of basal melanin. furthermore, sox-10 and melan-a showed absence of melanocytes while colloidal iron stains with and without hyaluronidase demonstrated no increase in dermal mucin. these findings, in conjunction with clinical presentation and wood lamp testing, were consistent with a diagnosis of vitiligo. in the context of the specific blaschkoid distribution of the depigmented macules and patches primarily on the right upper extremity, the timeline of the patient’s exposure to durvalumab, and absence of personal or family history of autoimmunity, we concluded that the patient was experiencing durvalumab-induced segmental vitiligo. the patient was started on narrow band uvb phototherapy twice weekly and triamcinolone 0.1% ointment twice daily, which immediately halted further progression of the depigmentation and has resulted in repigmentation of many areas over the past 4 months of treatment. figure 2. an additional linear arrangement of depigmented macules is seen on the left posterior neck immediately adjacent to midline. skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 721 understanding the proposed mechanism of checkpoint inhibitor-induced vitiligo requires an appreciation for the physiologic function of the programmed cell-death receptor pathway. pd-1 is a receptor expressed on the surface of t cells while its ligand, pdl-1, is found on dendritic cells and macrophages. the interaction ultimately leads to attenuation of the t-cell response. this pathway, in which t-cell response can be weakened, has an important role in cancer progression. some malignancies evolve to overexpress pdl-1, which weakens cytotoxic t cell response and allows malignant cells to evade immune response. thus, the pd-1/pdl-1 pathway is an excellent chemotherapy target as it restores the immune system ’s ability to combat malignant cells.3 utilization of this pathway, however, may come at a cost in regard to autoimmunity. segmental vitiligo is defined as depigmented macules affecting isolated body parts in a blaschkoid distribution (or embryonic epidermal cell migration patterns) that typically does not cross the midline4; however, in our patient, a small linear grouping does appear on the contralateral posterior neck. the significance of dermatological conditions that follow a blaschkoid distribution, while well documented, remains unclear. furthermore, the reason depigmentation in our patient follows this unique pattern is uncertain currently, and further investigation into this phenomenon is required. depigmented macules develop in vitiligo due to autoimmune t cell-mediated destruction of melanocytes. the proposed mechanism for pd-1 inhibitor-induced vitiligo suggests that immune effector cells target a shared antigen among malignant cells and healthy melanocytes. pd-1 inhibitors furthermore create an environment in which such autoimmune destruction remains unchecked. we hypothesize that a similar mechanism is at play in our patient with the affected melanocytes expressing a shared or similarappearing antigen with the patient’s small cell lung cancer due to genetic mosaicism. another possible explanation is that the affected cells are somehow less robust and are more prone to cellular death also due to genetic mosaicism. although checkpoint inhibitor-induced vitiligo is well established, our case report remains unique, as to our knowledge, durvalumab-induced segmental vitiligo has yet to be documented. durvalumab use has been associated with several dermatological conditions. fda clinical trial data showed that of 1,889 patients on durvalumab, 26% experienced rash or dermatitis with discontinuation of the drug occurring in 0.1%. only 0.3% of patients reported affliction with non-segmental vitiligo.5 it is important to accurately catalogue these dermatological reactions in order to optimize care for patients. vitiligo, both segmental and non-segmental, should be recognized as potential dermatological conditions associated with durvalumab use. further study regarding the significance of the segmental distribution is needed, though it does not appear to infer any deleterious consequences for our patient, as he is responding well to treatment. conflict of interest disclosures: none funding: none corresponding author: maansi kulkarni, ba boonshoft school of medicine wright state university 3640 col. glenn hwy dayton, oh 45436 email: kulkarni.31@wright.edu discussion conclusion skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 722 references: 1. syed yy. durvalumab: first global approval. drugs. 2017 aug;77(12):1369-1376 2. sun x, roudi r, dai t, chen s, fan b, li h, zhou y, zhou m, zhu b, yin c, li b, li x. immune-related adverse events associated with programmed cell death protein-1 and programmed cell death ligand 1 inhibitors for non-small cell lung cancer: a prisma systematic review and meta-analysis. bmc cancer. 2019 jun 10;19(1):558. 3. pardoll dm. the blockade of immune checkpoints in cancer immunotherapy. nat rev cancer. 2012 mar 22;12(4):252-64. 4. bolognia jl, orlow sj, glick sa. lines of blaschko. j am acad dermatol. 1994 aug;31(2 pt 1):157-90. 5. ellis sr, vierra at, millsop jw, lacouture me, kiuru m. dermatologic toxicities to immune checkpoint inhibitor therapy: a review of histopathologic features. j am acad dermatol. 2020 oct;83(4):1130-1143. powerpoint presentation safety of tralokinumab in pediatric patients aged 12–17 years with moderate-to-severe atopic dermatitis: results from the phase 3 ecztra 6 trial andreas wollenberg1,2, michael cork3, carsten flohr4, anthony bewley5, andrew blauvelt6, chih-ho hong7, shinichi imafuku8, marie l.a. schuttelaar9, eric l. simpson10, weily soong11, petra amoudruz12, katja wendicke lophaven12, azra kurbasic12, lise soldbro12, natacha strange vest12, amy paller13 1ludwig maximilian university of munich, department of dermatology and allergy, munich, germany; 2vrije universiteit brussel (vub), universitair ziekenhuis brussel (uz brussel), department of dermatology, brussels, belgium; 3sheffield dermatology research, department of infection, immunity, and cardiovascular disease, the university of sheffield and sheffield teaching hospitals, nihr clinical research facility, sheffield, uk; 4department of paediatric dermatology, st john's institute of dermatology, guy's & st thomas' nhs foundation trust and king's college london, london, uk; 5barts health nhs trust, london, uk; 6oregon medical research center, portland, or, usa; 7university of british columbia, vancouver, bc, canada; 8fukuoka university, fukuoka, japan; 9university medical centre groningen, university of groningen, groningen, the netherlands; 10oregon health & science university, portland, or, usa; 11allervie health-alabama allergy & asthma center, birmingham, al, usa; 12leo pharma, a/s, ballerup, denmark; 13feinberg school of medicine, northwestern university, chicago, il, usa materials and methods study design • adolescent patients were randomized 1:1:1 to subcutaneous tralokinumab 150 mg or 300 mg every 2 weeks (q2w), or placebo for an initial treatment period of 16 weeks • primary endpoints were investigator’s global assessment (iga) score 0/1 and ≥75% improvement from baseline in eczema area and severity index (easi-75) at week 16 • patients achieving primary endpoints without rescue treatment were re-randomized to tralokinumab q2w or every 4 weeks (q4w), at their same initial tralokinumab dosage for 36 weeks of maintenance treatment as shown in figure 1, while placebo responders continue in the placebo q2w • patients not achieving primary endpoints at week 16, those receiving rescue treatment from week 2 to week 16, and those meeting other specific criteria† were transferred to open-label treatment of tralokinumab 300 mg q2w plus optional mild-to-moderate strength topical corticosteroids (tcs) • key secondary endpoints include change in scoring ad (scorad) from baseline to week 16, reduction of worst daily pruritus numeric rating scale (nrs) (weekly average) of at least 4 from baseline to week 16, and change in children's dermatology life quality index (cdlqi) score from baseline to week 16 objective • to present detailed safety data up to 52 weeks for tralokinumab in pediatric patients aged 12–17 years with moderate-to-severe ad enrolled in the ecztra 6 trial (nct03526861) patient characteristics • baseline demographic and clinical characteristics were comparable across treatment groups (table 1) results • tralokinumab was well tolerated in pediatric patients aged 12–17 years with moderate-to-severe ad, with a favorable safety profile seen through 52 weeks of treatment • the safety profile was similar to that seen in adult phase 3 studies, with the frequency and type of aes being generally consistent9,10 • the frequency of conjunctivitis was low and similar between the tralokinumab and placebo arms at week 16, with no increase observed up to week 52 • the frequency of acne was low across tralokinumab and placebo arms, supporting a favorable tolerability profile of tralokinumab in this age group • the detailed long-term safety data presented here add to the previous findings that tralokinumab is efficacious and well tolerated in this adolescent patient group8 conclusions introduction • atopic dermatitis (ad) is a chronic inflammatory skin disease associated with a substantial disease burden; it often develops in early childhood and affects up to 20% of children1,2 • there are limited safe and effective treatment options available for long-term use in pediatric patients with moderate-to-severe ad • tralokinumab is a fully human, high-affinity, monoclonal antibody that specifically neutralizes interleukin-13, a key driver of inflammation, skin barrier dysfunction and microbial dysbiosis in ad3–7 • in the phase 3 ecztra 6 monotherapy trial, tralokinumab was effective and well tolerated in patients aged 12–17 years with ad8 tralokinumab 300 mg q2w placebo q2w tralokinumab 300 mg q2w tralokinumab 300 mg q4w alternating with placebo placebo q2w tralokinumab 300 mg q2w optional tcs and optional home use initial treatmentscreening maintenance treatment patients with clinical response iga 0/1 or easi-75 clinical response must be achieved without rescue safety follow-up open-label treatment 1:1:1 randomization patients who: • did not achieve iga 0/1 or easi-75 at week 16 • received rescue treatment between week 2–16 • were transferred from maintenance treatment if specific criteria were met washout of tcs and other ad medication initial loading dose 1:1 randomization 16 weeks0–6 weeks 52 weeks 66 weeks 1:1 randomization tralokinumab 150 mg q2w tralokinumab 150 mg q2w tralokinumab 150 mg q4w alternating with placebo n=294 figure 1. ecztra 6 trial design rescue treatment during initial and maintenance treatment defined as: tci, tcs or systemic ad treatment. ad, atopic dermatitis; easi, eczema area and severity index; iga, investigator’s global assessment; q2w, every 2 weeks; q4w, every 4 weeks; tcs, topical corticosteroids. †patients not achieving easi-75 over ≥4 weeks with iga ≥2 after iga=0 at week 16, or with iga ≥3 after iga=1 at week 16, or who had iga >1 at week 16; patients who receive rescue treatment after week 16 table 1. baseline characteristics patients placebo (n=94) tralokinumab 150 mg q2w (n=98) tralokinumab 300 mg q2w (n=97) mean age, years 14.3 14.8 14.6 age group, n (%) 12–14 15–17 49 (52.1) 45 (47.9) 37 (37.8) 61 (62.2) 45 (46.4) 52 (53.6) male sex, n (%) 51 (54.3) 51 (52.0) 47 (48.5) mean duration of ad, years (sd) 12.1 (3.5) 12.7 (3.7) 12.1 (3.7) severe disease (iga=4), n (%) 43 (45.7) 44 (44.9) 48 (49.5) mean easi (sd) 31.2 (14.5) 32.1 (12.9) 31.8 (13.9) mean scorad (sd) 67.4 (14.9) 67.7 (14.4) 68.3 (13.7) mean cdlqi (sd) 13.3 (6.0) 12.9 (6.3) 13.4 (7.3) mean weekly average peak pruritus nrs (sd) 7.5 (1.7) 7.5 (1.6) 7.8 (1.5) ad, atopic dermatitis; cdlqi, children's dermatology life quality index; easi, eczema area and severity index; iga, investigator's global assessment; n, number of subjects in analysis set; nrs, numeric rating scale; q2w, every 2 weeks; scorad, scoring atopic dermatitis; sd, standard deviation. overall summary of aes: weeks 0-16 • tralokinumab was well-tolerated and rates of adverse events (aes) were similar in the pooled tralokinumab and placebo arms (majority were mild or moderate in severity) (table 2) • no patterns were seen in types of serious aes and none led to any safety concerns (table 2) • the majority of aes had resolved within the initial 16-week period; only one ae led to treatment withdrawal and was not considered related to treatment* (table 2) table 4. ecztra 6 safety summary (weeks 0-52) rate: number of events divided by patient years of exposure x 100 ae, adverse event; aesi, adverse event of special interest; imp, investigational medicinal product; n, number of subjects in analysis set; q2w, every 2 weeks; q4w, every 4 weeks; sae, serious adverse event; tcs, topical corticosteroid. overall summary of aes: weeks 0–52 • during weeks 16–52, the types and frequencies of aes were similar to the initial phase, with the majority being non-serious and mild or moderate in severity (table 4) references 1. peters as, et al. j allergy clin immunol. 2010;126:590–95. 2. weidinger s, et al. nat rev dis primers. 2018;4:1. 3. bieber t. allergy. 2020;75:54–62. 4. furue k, et al. immunology. 2019;158:281–86. 5. szegedi k, et al. jeadv. 2015;29:2136–44. 6. tsoi lc, et al. j invest dermatol. 2019;139:1480–89. 7. popovic b, et al. j mol biol. 2017;429:208–19. 8. paller a, et al. 2021 fall clinical dermatology conference. 9. wollenberg a et al. br j dermatol. 2021;184:437–49; 10. silverberg ji et al. br j dermatol. 2021;184:45063. disclosures andreas wollenberg has received grants, personal fees, or nonfinancial support from abbvie, aileens, almirall, beiersdorf, bioderma, chugai, galapagos, galderma, gsk, hans karrer, leo pharma, lilly, l’oreal, maruho, medimmune, merck, novartis, pfizer, pierre fabre, regeneron, santen, and sanofi-aventis. michael cork has served as a clinical trial investigator for astellas, galapagos, johnson & johnson, leo pharma, la roche-posay, msd, novartis, perrigo, regeneron, sanofi genzyme, and stiefel; has served as an advisory board member, consultant, and/or invited lecturer for pfizer inc., amgen, astellas, bayer, johnson & johnson, leo pharma, l’oréal, msd, novartis, regeneron, sanofi genzyme, stiefel, and unilever; has received honoraria from astellas, johnson & johnson, leo pharma, novartis, regeneron, sanofi genzyme, and stiefel; and has received research funding from bayer. carsten flohr is chief investigator of the uk national institute for health research-funded treat (isrctn15837754) and softer (clinicaltrials.gov nct03270566) trials as well as the uk-irish atopic eczema systemic therapy register (a-star; isrctn11210918) and a principal investigator in the european union (eu) horizon 2020funded biomap consortium (http://www.biomap-imi.eu/). he also leads the eu trans-foods consortium. his department has received funding from both sanofi-genzyme and pfizer for skin microbiome work. anthony bewley has been a consultant for and received consultancy fees or travel bursaries from abbvie, almiral, eli lilly, galderma, janssen, leo pharma, novartis, sanofi, and ucb pharma. andrew blauvelt has served as a speaker/received honoraria from abbvie and ucb, served as a scientific adviser/received honoraria from abbvie, abcentra, aligos, almirall, amgen, anaptysbio, arcutis, arena, aslan, athenex, boehringer ingelheim, bristol-myers squibb, dermavant, ecor1, eli lilly and company, evommune, forte, galderma, highlightii pharma, incyte, janssen, landos, leo, merck, novartis, pfizer, rapt, regeneron, sanofi genzyme, sun pharma, ucb pharma, vibliome, and xencor, and has acted as a clinical study investigator/institution has received clinical study funds from abbvie, amgen, arcutis, athenex, boehringer ingelheim, bristol-myers squibb, dermavant, eli lilly and company, galderma, incyte, janssen, leo, merck, novartis, pfizer, regeneron, sun pharma, and ucb. chih-ho hong is a researcher, consultant, and/or advisor for abbvie, amgen, arcutis, bausch health, boehringer ingelheim, celgene, dermavant, dermira, ds biopharma, galderma, glaxosmithkline, incyte, janssen, leo pharma, lilly, medimmune, novartis, pfizer, regeneron, roche, sanofi genzyme, sun pharma, and ucb. shinichi imafuku is a researcher, consultant, or speaker for abbvie, amgen, boehringer ingelheim, celgene, daiichisankyo, eisai, kyowakirin, lilly, taihoyakuhinkogyo, tanabemitsubishi, tsumura, torii, maruho, novartis, leo pharma, and janssen. marie l.a. schuttelaar has served on advisory boards for sanofi genzyme, pfizer, leo pharma, eli lilly, galderma, and abbvie; as an investigator for abbvie, novartis, regeneron pharmaceuticals, inc., sanofi genzyme, and galderma; as a consultant for regeneron pharmaceuticals, inc.; has received research grants from sanofi genzyme and novartis. eric l. simpson is a consultant and investigator for regeneron/sanofi, dermira, menlo pharmaceuticals, lilly, abbvie, genentech, medimmune, gsk, leo pharma, celgene, and pfizer. weily soong has served on the advisory board and received research grants from abbvie, leo pharma, genentech, inc., teva, novartis, and pfizer; served on the advisory board, received research grants, and was a speaker for amgen, astrazeneca, regeneron, sanofi, and glaxosmithkline; received research grants and was a speaker for optinose; received research grants from aimmune, avillion, galderma, gossamer bio, 3m, and leo pharma. petra arlert, katja wendicke lophaven, azra kurbasic, lise soldbro and natacha strange vest are employees of leo pharma a/s. amy paller has served as an investigator for abbvie, anaptysbio, incyte, janssen, krystalbio, leo pharma, regeneron, and ucb, received honorarium for consultancy from abbvie, abeona, almirall, anaptysbio, arena, azitra, biomx, boehringer ingelheim, castle biosciences, catawba, dermira, exicure, forté, kamari, leo pharma, lilly, lifemax, novartis, pfizer, regeneron, sanofi genzyme, seanergy, and ucb, and served on a data safety monitory board for abbvie, bausch, galderma, and novan. acknowledgements the ecztra 6 clinical trial was sponsored by leo pharma a/s (ballerup, denmark). this poster is an encore of a previous presentation at european academy of dermatology and venereology 31st annual meeting, 7–10 september 2022. editorial support from alphabet health (new york, ny, usa) by juliel espinosa, phd and meredith whitaker, phd was funded by leo pharma (usa). scan to download a copy of this poster copies of this poster and its content, obtained through this qr code, are for personal use only and may not be reproduced without written permission from the authors placebo (n=94) tralokinumab 150/300 mg q2w (n=195) n (%) rate n (%) rate patients with ≥1 aes 58 (61.7) 479.7 129 (66.2) 518.6 patients with ≥1 serious aes 5 (5.3) 17.9 4 (2.1) 6.8 severity of aes mild 40 (42.6) 275.7 95 (48.7) 323.1 moderate 31 (33.0) 179.0 65 (33.3) 171.7 severe 7 (7.4) 25.1 8 (4.1) 23.8 related to imp 20 (21.3) 128.9 51 (26.2) 158.1 leading to withdrawal 0 0 1 (0.5)* 1.7 outcome fatal 0 0 0 0 not recovered/not resolved 7 (7.4) 25.1 11 (5.6) 22.1 recovering/resolving 2 (2.1) 7.2 5 (2.6) 10.2 recovered/resolved 55 (58.5) 433.2 122 (62.6) 481.2 recovered/resolved with sequelae 3 (3.2) 10.7 1 (0.5) 1.7 unknown 1 (1.1) 3.6 2 (1.0) 3.4 table 2. ecztra 6 safety summary (weeks 0-16) *cerebrovascular accident, not considered related to treatment by the investigator or study sponsor; the patient had several risk factors for developing cerebrovascular accident. the event was not considered related to treatment with tralokinumab by either investigator or sponsor/leo. the outcome was reported as recovered with sequelae. rate: number of events divided by patient years of exposure x 100 ae, adverse event; imp, investigational medicinal product; n, number of patients with one or more events. frequently reported aes: weeks 0–16 • the most frequently reported aes in adolescents were similar to those seen in adults (figure 2) figure 2. aes during the initial treatment phase (≥5% of patients in pooled tralokinumab or placebo arms) viral urtis were most commonly reported as the common cold urti, upper respiratory tract infection 8.5 12.8 4.3 3.2 5.3 4.3 15.9 10.3 9.7 5.6 1.5 1.5 0 2 4 6 8 10 12 14 16 18 viral urti (resp. inf.) atopic dermatitis urti (resp. inf.) headache asthma acne placebo (n=94) tralokinumab 150/300 mg q2w (n=195) p a ti e n ts ( % ) frequency of conjunctivitis aesi: weeks 0–16 • the frequency of conjunctivitis was low and similar between the pooled tralokinumab and placebo arms; only 2 cases of conjunctivitis (pt) occurred, both in the tralokinumab 150 mg arm (table 3) placebo (n=94) tralokinumab 150/300 mg q2w (n=195) n (%) rate n (%) rate conjunctivitis (aesi) 2 (2.1) 10.7 7 (3.6) 11.9 conjunctivitis (pt) 0 0 2 (1.0) 3.4 conjunctivitis bacterial (pt) 0 0 1 (0.5) 1.7 conjunctivitis allergic (pt) 2 (2.1) 10.7 4 (2.1) 6.8 conjunctivitis viral (pt) 0 0 0 0 rate: number of events divided by patient years of exposure x 100 aesi, adverse event of special interest; pt, preferred term additional adverse events of relevance: weeks 0–16 • eczema herpeticum was reported in 2 patients in the initial treatment phase (1 in placebo and 1 in tralokinumab 150 mg q2w arm) • no patients had eczema herpeticum in the tralokinumab 300 mg q2w arm • herpes simplex infections were reported in 4 patients in the initial treatment phase (2 in placebo and 2 in the tralokinumab 150 mg q2w arm) • no patients had herpes simplex infections in the tralokinumab 300 mg q2w arm • there were no reports of swelling related to joints, enthesitis, tenosynovitis, generalized joint pain, or psoriasis • there was one case of right hip pain (coded as arthralgia), starting at day 4 after loading dose, mild, not considered related to treatment, resolved after 3 days without any action taken initial phase (weeks 0–16) maintenance phase (weeks 16–52) open-label phase (weeks 16–52) tralokinumab 150/300 mg q2w (n=195) tralokinumab 150/300 mg q2/4w (n=50) tralokinumab 300 mg q2w plus optional tcs (n=234) n (%) rate n (%) rate n (%) rate patients with ≥1 ae 129 (66.2) 518.6 28 (56.0) 205.4 158 (67.5) 349.4 patients with ≥1 sae 4 (2.1) 6.8 0 0 7 (3.0) 4.63 severity mild 95 (48.7) 323.1 16 (32.0) 90.83 122 (52.1) 238.9 moderate 65 (33.3) 171.7 19 (38.0) 110.6 82 (35.0) 107.9 severe 8 (4.1) 23.8 1 (2.0) 3.95 4 (1.7) 2.7 related to imp 51 (26.2) 158.1 10 (20.0) 75.03 65 (27.8) 107.2 conjunctivitis (aesi) 4 (4.1) 13.6 3 (6.0) 11.85 11 (4.7) 9.3 • secondary endpoints, change from baseline in scorad and cdlqi were analyzed using a linear mixed model for repeated measurements • data after use of rescue or discontinuation were disregarded • a closed testing procedure with hierarchical tests, alpha splitting, and alpha recycling were applied for above efficacy endpoints statistical analyses and endpoints • easi-75, iga 0/1, and secondary endpoint ≥4-point improvement in adolescent pruritus nrs were analyzed using cochran-mantel-haenszel test stratified by geographic region and baseline disease severity • patients receiving rescue therapy between week 2 and 16 or with missing data at week 16 were considered non-responders table 3. frequency of conjunctivitis aesi slide 1: safety of tralokinumab in pediatric patients aged 12–17 years with moderate-to-severe atopic dermatitis: results from the phase 3 ecztra 6 trial patient preference for calcipotriene 0.005%/betamethasone dipropionate 0.064% foam or topical suspension vs. latest topical treatment in the pso-insightful study jennifer soung, md,1 lisa tiu, pharmd,2 karen veverka, phd,2 chih-ho hong, md3 1southern california dermatology; 2leo pharma inc; 3university of british columbia, department of dermatology and skin science and probity medical research introduction results conclusions materials & methods acknowledgements references � topical therapies are a mainstay in psoriasis vulgaris treatment and are used in combination therapy even in patients receiving systemic or biologic therapy � patient preference for vehicle formulation can impact adherence and, consequently, real-life effectiveness � the pso-insightful study was designed to assess patient-reported factors that influence preference following once-daily topical treatment with calcipotriene 0.005%/betamethasone dipropionate 0.064% (cal/bd) foam and gel1 � questionnaires (including topical product usability questionnaire, tpuq; comparison to latest topical treatment, cltt) were completed by patients at baseline and timepoints during the study to assess usability and preference differences pso-insightful study design � pso-insightful was a prospective, multicenter, phase iiib, open-label, randomized, two-arm crossover study including patients ≥18 years with mild-to-severe psoriasis of ≥6 months’ duration involving 2-30% bsa and mpasi of ≥2 (table 1) � after 4-week washout, 213 patients were randomized 1:1 to once-daily cal/bd foam for 1 week, followed by cal/bd gel for 1 week, or vice-versa (figure 1) figure 1: schematic of study design of pso-insightful, [nct02310646] 2 study assessments � patients completed questionnaires to assess therapy usability and preference differences o topical product usability questionnaire (tpuq) o comparison to latest topical treatment (cltt) all patients n = 212 (%) age category, n (%) 18 – 39 years 48 (22.6) 40 – 59 years 92 (43.4) ≥ 60 years 72 (34.0) male : female, n (%) 133:79 (63:37) bmi, n (%) < 25 kg/m2 37 (17.5) 25 – 30 kg/m2 73 (34.4) > 30 kg/m2 102 (48.1) pga, n (%) mild 61 (28.8) moderate 122 (57.5) severe 29 (13.7) duration of psoriasis, n (%) < 2 years 4 (1.9) 2 – 5 years 30 (14.2) > 5 years 178 (84.0) bsa, n (%) < 4% 93 (43.9) 4 – 6% 56 (26.4) 6 – 11% 38 (17.9) 11 – 15% 11 (5.2) ≥ 15% 14 (6.6) mpasi, n (%) 2 – 5 86 (40.6) 5.1 – 10 91 (42.9) > 10 35 (16.5) mean dlqi 7.8 localized:widespread distribution of psoriasis, % 62:38 table 1. patient demographics and baseline characteristics (adapted from pso-insightful) bmi, body mass index; bsa, body surface area; mpasi, modified psoriasis and severity index; pga, physician’s global assessment of disease severity � full analysis set comprised all randomized patients who completed an on-study questionnaire � ltt analysis set comprised all randomized patients who had used topical treatment within 3 months before baseline statistical analysis topical product usability questionnaire (tpuq) � each patient assessed the extent to which they agreed with each of the 26 items using 5-point scale (-2 to 2), organized into four domains: “application”, “formulation”, “container”, “satisfaction,” regarding product usability. � frequency: o following randomization, the tpuq was used to assess the ltt at baseline o during visits to the clinic at the end of weeks 1 and 2, patients completed tpuq based on their treatment experience during the previous 7 days comparison to latest topical treatment (cltt) � patients stated whether they preferred their ltt or cal/bd foam/gel, or had no preference � frequency: o during visits to the clinic at the end of weeks 1 and 2, patients completed cltt based on their treatment experience during the previous 7 days � overall, patients from the pso-insightful study had stronger preferences for either cal/bd foam or gel as compared to their last topical treatment � these results from the topical product usability questionnaire are further corroborated with the similar results in the comparison to latest topical treatment survey � the significant differences observed in favor of cal/bd foam as compared to the topical suspension formulation are related mainly to application and a “feeling of relief” which may be attributable to the vehicle � these data provide insight into aspects of topical product usability, but more robust research is necessary to obtain a complete understanding ltt (n=118) cal/bd foam (n=116) cal/bd topical suspension (n=115) application domain scores ease of application 1.4 1.2 1.5 ease of application on lesion only 1.3 0.9* 1.4 ease of spreading 1.5 1.5 1.7* lack of mess 0.6 0.9 1.0** good for use on small areas 1.1 1.0 1.4* good for use on large areas 0.9 1.4*** 1.5*** quick to apply 1.2 1.5** 1.3 total time spent acceptable 1.1 1.6*** 1.4** easily incorporated into daily routine 1.0 1.5*** 1.4*** formulation domain scores quickly absorbed 0.2 0.7** 0.6** dried quickly 0 0.5** 0.4** immediate feeling of relief 0.1 1.1*** 0.7*** felt soothing 0.6 1.3*** 1.0** appealing to touch 0.2 1.0*** 0.9*** felt moisturizing 0.6 1.3*** 1.2*** not greasy –0.5 0.2*** 0.2*** odourless 1.2 1.3 1.5** no staining 0.4 0.9** 0.9*** container domain scores easy to get medication out of container 1.3 1.2 1.3 easy to use 1.3 1.2 1.4 easy to keep clean 1.1 1.3 1.3 accurately dispense wanted amount 1.0 0.9 1.5*** satisfaction domain scores confidence in using 0.6 1.3*** 1.2*** would use regularly 0.9 1.4** 1.3* would recommend 0.4 1.3*** 1.0*** overall satisfaction 0.3 1.2*** 1.1*** table 2. mean tpuq scores compared with llt, by domain, for cal/bd foam and topical suspension range: –2, strongly disagree to +2, strongly agree *p<0.05; **p<0.01; ***p<0.001 vs ltt. ltt included various corticosteroids (of different potencies) and combination products, with similar types of products in all categories (ointment, cream, ‘other’) cal/bd foam or cal/bd topical suspension vs. ltt: � mean tpuq domain scores were often significantly in favor of both cal/bd foam and topical suspension compared with ltt � scores for cal/bd topical suspension were generally higher than for ltt � most scores for cal/bd foam were higher, although some related to ease of application and container items were comparable to ltt cal/bd foam vs. cal/bd topical suspension: � mean application, container and satisfaction domain scores were high for both cal/bd foam and gel � both cal/bd foam and cal/bd gel had very high application domain scores for: o good for use on large areas o total time spent acceptable o quick to apply o easily incorporated into daily routine � significant differences observed in favor of cal/bd foam vs topical suspension in the domains of “immediate feeling of relief” and “soothing feeling” � significant differences observed in favor of cal/bd topical suspension vs foam included: o ease of application, ease of application on lesion only, and ease of spreading o good for use on small areas o odorless o accurately dispensed wanted amount cal/bd foam (n=212) cal/bd topical suspension (n=212) p value application domain scores ease of application 1.1 1.5 ** ease of application on lesion only 0.9 1.4 *** ease of spreading 1.5 1.7 ** lack of mess 0.8 1.0 ns good for use on small areas 1.0 1.4 *** good for use on large areas 1.4 1.5 ns quick to apply 1.4 1.4 ns total time spent acceptable 1.5 1.5 ns easily incorporated into daily routine 1.4 1.5 ns formulation domain scores quickly absorbed 0.7 0.7 ns dried quickly 0.5 0.5 ns immediate feeling of relief 1.0 0.7 ** felt soothing 1.2 1.0 ** appealing to touch 0.9 0.9 ns felt moisturizing 1.1 1.2 ns not greasy 0 0.3 * odourless 1.3 1.6 *** no staining 1.0 1.0 ns container domain scores easy to get medication out of container 1.1 1.3 ns easy to use 1.1 1.4 *** easy to keep clean 1.2 1.4 * accurately dispense wanted amount 0.9 1.5 *** satisfaction domain scores confidence in using 1.2 1.2 ns would use regularly 1.3 1.3 ns would recommend 1.2 1.1 ns overall satisfaction 1.1 1.2 ns range: –2, strongly disagree to +2, strongly agree *p<0.05; **p<0.01; ***p<0.001 table 3. mean tpuq scores, by domain, for cal/bd foam and topical suspension poster presented at the fall clinical dermatology conference, las vegas, nv; october 12th – 15th, 2017 all patients; foam-gel* localized (n = 128) 0.5 ± 8.8 widespread (n = 78) -2.1 ± 8.2 all patients (n = 204) -0.5 ± 8.2 *negative difference indicates preference for gel table 4. difference in total formulation score (tpuq) between study treatments by psoriasis distribution phenotype (fas) differences in tpuq scores between study treatments by psoriasis distribution � the forward selection procedure identified psoriasis distribution as a significant factor � trend towards more favorable scores for cal/bd foam in patients with localized distribution and in favor of gel for patients with widespread distribution 1 hong c-h, papp ka, lophaven kw, et al. patients with psoriasis have different preferences for topical therapy, highlighting the importance of individualized treatment approaches: randomized phase iiib pso-insightful study [submitted]. 2 clinicaltrials.gov. bethesda (md): national library of medicine (us). 2017 jun 1. identifier: nct02310646. patient insights following use of leo 90100 aerosol foam and daivobet® gel in subjects with psoriasis vulgaris. https://clinicaltrials.gov/ct2/show/nct02310646?term=nct02310646&rank=1 this study was sponsored by leo pharma; editorial support was provided by dharm patel, phd at leo pharma inc. us. fc17posterleosoungpatientpreference.pdf skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 727 brief article psoriasiform spongiotic dermatitis drug eruption following pfizer-biontech sars-cov-2 mrna vaccine administration kevin h. nguyen, ms1, diem q. pham, do1, christof p. erickson, md2 1 western university of health sciences college of osteopathic medicine of the pacific, pomona, ca 2 compass dermatopathology, san diego, ca since december 2020, over two billion vaccines have been administered to combat the coronavirus disease 2019 (covid-19) pandemic.1 there have been few reports of cutaneous reactions succeeding vaccination. rice et al reported that localized cutaneous erythema and swelling was commonly observed in the covid-19 vaccine clinical trials.2 recent case reports have documented the findings of lichen planus, morbilliform rashes, injection site patches, and radiation recall after covid-19 vaccine administration.3–7 here we present a morbilliform drug eruption akin to the sequelae of the covid-19 pfizer-biontech sars-cov-2 mrna vaccine. a 51-year-old caucasian female with a history of hypertension, diabetes mellitus, and psoriasis vulgaris with plaques confined abstract introduction: cutaneous manifestations such as morbilliform rashes, lichen planus, and local injection site patches have been recently published in case reports to occur within days of receiving the coronavirus disease 2019 (covid-19) vaccine. the most common drug eruptions have been noted to be delayed hypersensitivity reactions. objective: to spotlight a vaccine drug eruption case in a patient with a long history of the autoimmune condition, psoriasis vulgaris. case presentation: a 51-year-old caucasian female presented with pruritic and erythematous rashes covering her back, abdomen, pelvis, and both upper extremities emerging one week after receiving the pfizer biontech mrna vaccine. the rashes worsened, rapidly spreading toward the lower extremities within five days after her second dose. the patient was diagnosed with psoriasiform spongiotic dermatitis compatible with a drug eruption and began loratadine and clobetasol cream treatment and phototherapy. conclusion: with limited published data available on skin reactions to the covid-19 vaccine, our case report is among one of the first presentations to describe a morbilliform rash induced by a pfizer biontech mrna drug-eruption. although this is a rare case, we may expect more reported drug eruptions to be documented as mass vaccinations continue to be dispensed across the globe. physicians must be prepared to accurately diagnose and treat dermatologic conditions on patients with and without pre-existing illnesses. introduction case report skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 728 to her elbows and knees presented with pruritic and erythematous rashes covering the abdomen, pelvis, back, upper, and lower extremities. the rashes on the proximal upper extremities, abdomen, pelvis, and back appeared one week after receiving the first pfizer-biontech sars-cov-2 mrna and remained unresolved. the rashes spread to the lower extremities five days after the second vaccine which progressively worsened since the onset of one and a half months prior to presentation. the patient endorsed dry skin, itching, and inflammation and denied difficulty swallowing, palpitations, visual disturbance, and coughing. prior to vaccination, the patient denied a history of any similar skin eruptions. she reported that these lesions were distinct in location and appearance to her history of plaque psoriasis at the elbow and knee regions. the patient denied any other provoking factors at the time of vaccination. a review of systems revealed recent sinus infection. figure 1. pink, scaly papules and plaques on the bilateral lower extremities multiple scattered pink scaly papules and plaques were found on the pelvis, back, and abdomen. furthermore, pink and red, nonscaly, smooth papules and plaques was observed on the bilateral upper and lower extremities (figure 1). a 4 mm punch biopsy on the left flank revealed probable guttate (eruptive) psoriasis infection on the pelvis, abdomen and back. histology showed slight acanthosis, focal loss of the granular layer, focal mounds of parakeratosis containing rare neutrophils, and a sparse infiltrate of lymphocytes in the upper dermis. lab blood work and urinalysis remained unremarkable. we attributed the guttate psoriasis to sinusitis, therefore, amoxicillin treatment was prescribed for ten days. however, due to continued flare up, amoxicillin was discontinued within seven days. 10 mg loratadine qam qd, 0.05% clobetasol topical cream bid, 25 mg hydroxyzine hcl prn and mild phototherapy was prescribed for treatment of the rashes on the extremities. figure 2. psoriasiform drug eruption: psoriasiform hyperplasia of the epidermis with suprapapillary thinning, focal diminution of the granular layer, parakeratosis with a few neutrophils, and focal spongiosis. rare eosinophils were also seen in the dermis (h&e 200x). skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 729 during a one-month follow-up, the patient experienced progressive resolution of the rashes, however, lesions on her extremities resurfaced sporadically. a second 4 mm punch biopsy on the right medial thigh favored the diagnosis of psoriasiform spongiotic drug eruption over guttate psoriasis. histology revealed psoriasiform hyperplasia of the epidermis with suprapapillary thinning, focal diminution of the granular layer, parakeratosis with a few neutrophils, and focal spongiosis (figure 2). a lymphohistiocytic infiltrate with rare eosinophils was present in the upper dermis. the patient reported clearance of the rashes and decreased pruritus (figure 3). still, 10 mg loratadine qam qd and 0.05% clobetasol cream prn bid was continued. hydroxyzine was discontinued due to drowsiness. no flare ups have occurred since the initial treatment was introduced, and the patient is recovering gradually. upon a one-year follow-up visit, the patient denied any recent exacerbating episodes. she has discontinued loratadine and clobetasol cream and has begun using a combined calcipotriene and betamethasone dipropionate foam topical for her plaque psoriasis which was still limited to the elbow and knee regions. overall, the patient is doing well and did not report any new skin eruptions. figure 3. improvement and clearing of rashes following phototherapy, loratadine, and clobetasol. prior to her presentation at the clinic, the patient reported that she had not been followed by a dermatologist within the past 10 years due to her lesions being wellcontrolled. she stated that throughout her 17year history of psoriasis, the plaques were controlled with topical fluticasone prescribed by her primary care physician. she reported chronic plaque psoriasis isolated at the elbows and knees throughout her clinical history. although constantly present, the patient denied any exacerbating factors or episodes of uncontrollable eruptions. however, she stated that the plaque psoriasis predictably presented each year with more scale throughout the winter season discussion skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 730 while having mild resolution during the summer and when exposed to water. the skin lesions that appeared after vaccination did not resemble her plaque psoriasis with respect to the location of occurrence or appearance. the differential diagnosis included guttate psoriasis, drug eruption, and allergic contact dermatitis. despite discontinuing all unnecessary medications, rashes remained unresolved. a biopsy of the left flank which revealed pink, scaly plaques and papules, confirmed guttate psoriasis as the cause of the lesions on the pelvis, back, and abdomen. despite amoxicillin treatment, more lesions developed, thus, it was discontinued within seven days of use. nevertheless, an infection causing guttate psoriasis co-occurring with the drug eruption is noteworthy to consider. morbilliform rashes are common in hypersensitivity reactions that occur three days to three weeks after drug administration.8 likewise, there was both a seven and five-day delay in rash appearance after the injection of the first and second doses of the pfizer-biontech sars-cov-2 mrna vaccine, respectively. the exacerbation and expansion of pink and red, non-scaly, papules and plaques on the lower extremities ensuing the second dose reaffirmed a delayed immune response. furthermore, the patient’s histopathology taken from the right medial thigh revealed focal spongiosis, eosinophils at the dermis, and lymphohistiocytic infiltrate consistent with drug exanthem biopsies observed in the literature.9 few reports of morbilliform drug eruptions have been documented after vaccination. jedlowski and jedlowski presented an initial erythematous morbilliform rash drug eruption at the lower back appearing forty-eight hours after pfizer biontech covid-19 vaccine administration.4 the eruption expanded, covering the proximal extremities after the second dose.4 however, the lesions were described as macular, with appearance of papules and plaques, unlike our patient. recently reported morbilliform rashes have resolved without any necessary treatment.4,5 our patient’s history of psoriasis vulgaris presented a clinical challenge for management and care. prednisone is the conventional treatment for drug eruptions; however, our patient’s compromised immunity made this option unfeasible as it would lead to pustular psoriasis development and induce hospitalization. proper treatment was attributed to the use of loratadine, an antihistamine and clobetasol steroid treatment. mcmahon and colleague’s survey revealed that delayed large local eruptions, local injection site reactions, urticaria, and morbilliform eruptions were most commonly reported after receiving the moderna and pfizer vaccines.10 similar to sars-cov-2 mrna vaccination, morbilliform rashes have been reported to be spotted subsequent to infection.11 sars-cov-2 enters cells through angiotensin-converting enzyme 2 (ace2) which is expressed in skin.12 thus, it may be reasonable to speculate that sars-cov-2 can cause eruptions such as erythema, urticaria, and vesicle formation.8 since the start of the covid-19 pandemic, few reports discuss the proper treatment of vaccine-induced skin rashes. providers and dermatologists must be prepared to offer alternative treatment when traditional options are contraindicated in immunocompromised patients. as more vaccines become distributed around the world, further evidence conclusion skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 731 will emerge to specify proper treatment protocols for drug eruptions secondary to vaccine administration. this case report calls forth the importance of more studies being conducted in larger sample studies for better characterization of skin reactions caused by the covid-19 vaccine. conflict of interest disclosures: none funding: none corresponding author: kevin h. nguyen, ms college of osteopathic medicine of the pacific western university of health sciences 309 e 2nd st. pomona, ca 91766 email: kevin.nguyen2@westernu.edu references: 1. fda. fact sheet for healthcare provides administering vaccine (vaccination providers). emergency use authorization (eua) of the pfizer-biontech covid-19 vaccine to prevent coronavirus disease 2019 (covid-19). 2019, 1–37 (2019). 2. rice, s. m., ferree, s. d., mesinkovska, n. a. & kourosh, a. s. the art of prevention: covid-19 vaccine preparedness for the dermatologist. int. j. women’s dermatology 7, 209–212 (2021). 3. mintoff, d., pisani, d., betts, a. & scerri, l. sars-cov-2 mrna vaccine-associated fixed drug eruption. j. eur. acad. dermatol. venereol. 1–3 (2021) doi:10.1111/jdv.17390. 4. jedlowski, p. m. & jedlowski, m. f. morbilliform rash after administration of pfizer-biontech covid-19 mrna vaccine. dermatol. online j. 27, 0–3 (2021). 5. corbeddu, m. et al. transient cutaneous manifestations after administration of pfizerbiontech covid-19 vaccine: an italian single-centre case series. j. eur. acad. dermatology venereol. (2021) doi:10.1111/jdv.17268. 6. hiltun, i. et al. lichen planus arising after covid-19 vaccination. j. eur. acad. dermatology venereol. 5–6 (2021) doi:10.1111/jdv.17221. 7. soyfer, v., gutfield, o., shamai, s., schlocker, a. & merimski, o. since january 2020 elsevier has created a covid-19 resource centre with free information in english and mandarin on the novel coronavirus covid-. int. j. radiat. oncol. 1– 5 (2021). 8. fattori, a. et al. cutaneous manifestations in patients with coronavirus disease 2019: clinical and histological finding. hum. pathol. 107, 39–45 (2020). 9. singh, s. et al. assessment of histopathological features of maculopapular viral exanthem and drug-induced exanthem. j. cutan. pathol. 44, 1038–1048 (2017). 10. mcmahon, d. e. et al. cutaneous reactions reported after moderna and pfizer covid-19 vaccination : a registry-based study of 414 cases. j. am. acad. dermatology 85, 46–55 (2021). 11. kulkarni, r. b., lederman, y., afiari, a., savage, j. a. & jacob, j. morbilliform rash: an uncommon herald of sars-cov-2. cureus 12, 10–15 (2020). 12. ziegler, c. g. k. et al. sars-cov-2 receptor ace2 is an interferon-stimulated gene in human airway epithelial cells and is detected in specific cell subsets across tissues. cell 181, 1016-1035.e19 (2020). research poster presentation design © 2019 www.posterpresentations.com intralesional treatment of basal cell carcinoma in a genetically inducible mouse model nancy messier1, frédéric couture2, vanessa théberge1, mario harvey1, kenneth kobayashi3,4 1feldan therapeutics, quebec, pq, canada, 2transbiotech, levis, pq, canada, 3dermatology consultant to feldan therapeutics, 4department of medicine, university of ottawa, canada introduction results references acknowledgement conclusion the authors wish to thank james limacher, md, division of dermatology, university of toronto, for his generous expertise in dermatopathology and editorial review. (1) gold nb et al. sci rep. 2021 oct 5;11(1):19791. doi: 10.1038/s41598-021-98752-9 (2) juan hy et al. arch dermatol res (2022). https://doi.org/10.1007/s00403-02202447-8 (3) witmanowski h et al. adv dermatol allergol 2017; xxxiv (4): 381–387 (4) gorlin, rj. medicine (baltimore). 1987 mar; 66(2):98-113 (5) evans dg, ladusans ej, rimmer s et al. j med genet 1993; 30:460–4 (6) kimonis ve et al. am j med genet 1977; 69:299–308 (7) bree af et al. am j med genet a 2011; 155a:2091–7 (8) bakshi a et al. mol carcinog 2017 dec; 56(12): 2543–2557 (9) basset-seguin et al. j eur acad dermatol venereol 2014 may; 28(5):626-32 (10) ng jm, curran t. nat rev cancer. 2011;11(7):493-501. (11) peer e, tesanovic s, aberger f. cancers (basel). 2019; 11(4):538 (12) sekulic a et al. plos one. 2022 jan 14; 17(1) (13) sekulic a et al. j am acad dermatol 2015; 72:1021-6 (14) migden mr et al. cancer treatment reviews 64 (2018) 1–10 (15) sabol m et al. int j mol sci 2018; 19(9):2562. (16) pandolfi, s., & stecca, b. expert reviews in molecular medicine, 17, e5. doi:10.1017/erm.2015.3 (17) khoo abs et al. acta derm venereol 2019; 99: 1266–1269 we observed that intralesional treatment with the aso alone is not associated with tumor regression and in fact permits continued tumor growth (fig.7 and fig. 10 (d)). however, intralesional treatment of bccs in the inducible mouse model with the gli1 aso and feldan shuttle peptide combination (fld103) resulted in rapid and marked tumor regression, and sometimes complete eradication, over a few weeks (fig 10 (a), (b) and (c)). healthy perilesional skin in the mouse model appears unaffected by the treatment, demonstrating targeted treatment specificity. the healed skin appeared grossly normal. after recovery, histologic examination of treated sites showed partial bcc regression in some (fig.10 (c)), and no residual bcc in most. areas with no residual tumor showed complete healing of the epidermis, dermis and subcutaneous tissue and no obvious scarring (fig.10 (a) and (b)). twice a week intralesional treatment of mouse tumors (fig.9) seems more effective than weekly treatment (fig.8 and table 1) in these pre-clinical studies. it should be noted however that the tumors of these nbccs-like mice show faster growth compared to those observed in humans. this mouse model has a lesion doubling time of about 10 days compared to approximatively 150 days in humans (17). based on the data presented herein and this difference in bcc doubling times, twice a month or monthly intralesional treatment with fld103 could be effective in treating human nodular bccs, which are less aggressive than those seen in the nbccs-like mouse model. we have demonstrated the utility of a specific intralesional treatment for bcc in a genetically inducible mouse model. this alternative and novel treatment produces rapid results with normal healing of the treated site. this treatment could offer an attractive option for patients with multiple bccs who wish to avoid systemic treatments or multiple surgeries. figure 7. evolution of tumors. our objective was to evaluate an intralesional treatment for bcc based on the intracellular delivery of an aso targeting gli1 using the feldan shuttle technology. to test the efficacy of our treatment, we used our inducible nbccs-like mouse model, genetically modified at the level of the expression of the ptch1 and p53 genes in the skin. the inducible mouse model uses ptch1and p53-knockdown mice treated with tamoxifen and doxycycline, resulting in repression of the ptch1 and p53 proteins specifically at the level of the skin. induced mice were then irradiated with uvb three times a week until bccs appeared, between 16 to 28 weeks (figure 5 and 6). some of these bccs were treated twice a week with injections of the aso targeting the production of the gli1 protein, with and without the use of the “feldan shuttle" peptide and others only once a week with the aso and feldan shuttle peptide combination (fld103), composed of feldan shuttle (0.05%) and gli1 aso (0.05%), the process resulting in the introduction of the aso into the tumor cells. injections were performed using a syringe fitted with a 28g needle and 25 μl of either formulation in sterile phosphate buffered saline (pbs). the evolution of the tumors was monitored several times a week with caliper measurements and photography. following the treatments, mice were sacrificed, and the tumor site tissue was harvested and analyzed by both routine (h&e) and specialized (ihc, if) histologic methods. methods results gorlin syndrome, also known as nevoid basal cell carcinoma syndrome, is a rare genetic disorder with a prevalence of approximately 1 in 31,000 to 60,000 people (1,2,3), therefore affecting about 11,000 people in the us. people with gorlin syndrome are at increased lifetime risk of developing hundreds to thousands of cutaneous basal cell carcinoma (bcc) skin cancers, from a few dozen to hundreds every year. in addition, cutaneous anomalies, cysts of the jaws, abnormalities and tumors of multiple organ systems have been described in these patients (4,5,6,7). mutations that result in the up regulation of hedgehog (hh) signaling are associated with the development of bccs. mutations in the tumor suppressor gene patched (ptch1) are implicated in the growth of both sporadic bccs and those that develop in gorlin syndrome. ptch1 is a transmembrane receptor protein that suppresses the hedgehog (hh) signaling cascade. the majority of sporadic bccs have loss-of-function mutations in at least one allele of ptch1, resulting in loss of repression of the hh cascade, and others have gain-offunction mutations in smo, leading to over-activation of the pathway (8) (figure 1). figure 1. hedgehog pathway fig.2 . feldan shuttle mechanism of action currently, there is no cure for gorlin syndrome. dermatologic treatment centers on the prevention and management of cutaneous bcc tumors caused by the disease. the current treatment options consist of surgical excision, topical 5-fu and imiquimod, photodynamic therapy(9) or cryotherapy, often resulting in disfigurement. in addition, two systemic hedgehog pathway inhibitors (hpi) are approved for management of either metastatic and/or locally advanced and/or recurrent and/or surgically ineligible cutaneous bcc. these fda approved orally administered hpi are small molecules that target transmembrane components of the pathway, such as the protein smo. although these inhibitors effectively suppress hh signaling, early tumor resistance illustrates the need for treatments that target proteins located downstream in the pathway (10,11). in addition, these products are frequently associated with troublesome side effects when used long term (12,13), resulting in discontinuation of treatment in up to 70% of patients by 12 months (14). in addition to certain mutations in the sufu protein, located downstream to the ptch1 and smo proteins, non-canonical signaling also can lead to the activation of the gli1 protein and therefore of the hh pathway. this results in the development of bcc tumors that are unresponsive to traditional hedgehog inhibitors targeting smo protein activity. gli transcription factors play a central role in the intracellular signaling cascade as they are the primary mediators of the hh signaling pathway. as several authors have shown in recent studies, the downstream inhibition of gli1 in tumor therapy is more effective than the canonical upstream inhibition of smo (15,16). gli1 is therefore a target of great interest in the development of therapies against hh-dependent cancers, such as bcc. several inhibitors targeting gli1 are currently under development (3). feldan has selected this target, via the intracellular delivery of a gli1-specific antisense oligonucleotide (aso) (figure 3). the feldan shuttle, a second-generation cell penetrating peptide (cpp), is a 30 amino acid amphiphilic peptide developed by feldan to deliver different types of cargo of therapeutic interest into the cytoplasm of cells (figure 2 and 4). unlike first-generation cpps, the feldan shuttle’s unique characteristics facilitate release of endosomal contents into the cytoplasm. in conjunction with rapid catabolism of the shuttle peptide itself this results in any significant effect being strictly due to the intracellular presence of the cargo. figure 3. gli1 aso mechanism of action figure 4. intracellular delivery of a labeled aso adapted fromantisense_dna_oligonucleotide (biomedcentral.com) objective figure 5. lesions on induced nbccs mice figure 6. h&e of uninduced nbccs mouse skin a) and of a bcc lesion from induced nbccs mouse b) a) b) figure 9. evolution of tumors table 1. overall responses to intralesional injection after four weeks of treatment, based on analysis of images and caliper measurementsfigure 5. lesions on induced nbccs mice figure 6. h&e of (a) non-induced nbccs-like mouse skin (normal) and (b) a bcc in an induced nbccs-like mouse day 0 day 7 day 14 day 21 day 28 figure 8. evolution of tumors. day 0 day 7 day 14 day 21 day 28 m ou se # 52 35 m ou se # 50 21 m ou se # 50 32 figure 10. h&e of lesions after 28 days of intralesional treatment twice a week day 0 day 7 day 14 day 21 day 28 m ou se # 52 34 m ou se # 52 07 m ou se # 50 20 evolution of tumors during twice a week intralesional injection with 25 μl of fld103 (red circles identify treated lesions and blue circles identify untreated lesion) evolution of tumors during weekly intralesional injection with 25 μl of fld103 (red circles identify treated lesions) evolution of tumors during twice a week intralesional injection with 25 μl of gli1 aso (0.05%) alone (red circles identify treated lesions) financial disclosures the study was conducted by feldan therapeutics. nancy messier, vanessa théberge and mario harvey are employees of feldan therapeutics. frédéric couture is an employee of transbiotech. kenneth kobayashi is a consultant to feldan therapeutics and has received consultation fees. n = no. of bcc lesions gli1 aso alone twice a week (n=4) fld103 weekly (n=10) fld103 twice a week (n=12) complete 0 1 5 partial response 0 4 6 stable 1 2 0 progression 3 3 1 overall response (%) 0% 50% 92% (a) mouse #4446 (fld103 twice a week) (b) mouse #4699 (fld103 twice a week) complete regression of bcc complete regression of bcc (c) mouse #5235 (fld103 weekly) (d) mouse #5221 (gli1 aso alone twice a week) partial regression of bcc no regression of bcc https://doi.org/10.1007/s00403-022-02447-8 acknowledgements: medical writing support was provided by prescott medical communications group (chicago, il) with financial support from ortho dermatologics | presented at the fall clinical dermatology conference • october 17-20, 2019 • las vegas, nv synopsis ◾ psoriasis is a chronic, immune-mediated disease that varies widely in its clinical expression1 ◾ topical corticosteroids are the mainstay of treatment in psoriasis, but long-term safety remains a concern, limiting use, and posttreatment flare-up is common2 ◾ while psoriasis commonly affects lower extremities, treatment can be more problematic, and burden of disease heightened3,4 ◾ recent phase 3 clinical data have demonstrated that halobetasol propionate (hp) 0.01% lotion (byhalitm ortho dermatologics, bridgewater, nj) was significantly more effective than vehicle after 8 weeks of treatment in patients with moderate-to-severe localized plaque psoriasis,5,6 though efficacy in specific locations has not been reported objective ◾ to investigate the efficacy of once-daily hp 0.01% lotion versus vehicle in patients with moderateto-severe plaque psoriasis of the lower extremities methods study design ◾ data from two phase 3, multicenter, randomized, double-blind studies of patients with moderateto-severe psoriasis were pooled5,6 ◾ participants were randomized (2:1) to receive hp 0.01% lotion or vehicle once-daily for 8 weeks, with a 4-week posttreatment follow-up ◾ at baseline, participants were required to have investigator global assessment (iga) score of 3 or 4 (5-point scale; 0=clear and 4=severe) and body surface area (bsa) of 3% to 12% ◾ a post hoc analysis was conducted in a subset of patients with plaque psoriasis of the lower extremities, with a target lesion on the leg • for the target lesion, participants needed a score of ≥3 for at least 2 of 3 signs of psoriasis (erythema, plaque elevation, and scaling [5 point scale; 0=clear and 4=severe]), a sum of at least 8, and could not have a score of 0 or 1 in any one of the signs • target could not be on areas covering bony prominences (ie, knees); however, overall psoriasis assessment (iga and bsa) did not exclude the knees ◾ in these studies, cerave® hydrating cleanser and cerave® moisturizing lotion (l’oreal, ny) were provided as needed for optimal moisturization/cleaning of the skin efficacy assessments ◾ treatment success (≥2-grade improvement from baseline) in each individual sign of psoriasis (erythema, plaque elevation, and scaling) at the target lesion (leg) ◾ overall treatment success (≥2-grade improvement from baseline in iga score and a score of ‘clear’ or ‘almost clear’ [0 or 1]) ◾ improvements in overall mean bsa from baseline halobetasol 0.01% lotion in the treatment of moderate-to-severe plaque psoriasis of the lower extremities neal d bhatia, md1; tracey c vlahovic, dpm2; lawrence green, md3; gina martin, mot4; tina lin, pharmd5 1therapeutics clinical research, san diego, ca; 2temple university school of podiatric medicine, philadelphia, pa; 3department of dermatology, george washington university school of medicine, washington, dc; 4bausch health americas, inc., petaluma, ca; 5ortho dermatologics, bridgewater, nj ◾ reductions of ≥50% and ≥75% of overall igaxbsa from baseline (igaxbsa-50 and igaxbsa-75) at week 8 ◾ quality of life (qol) with 10 question dermatology life quality index (dlqi; 4-point scale; 0=not at all/not relevant and 3=very much) • mean change in dlqi of 4 was considered a minimal clinically important difference (mcid)7 results ◾ this analysis included 234 patients where leg was identified as the target lesion (hp 0.01% lotion, n=151; vehicle, n=83) ◾ at the end of the 8-week treatment period, more than half of participants receiving hp 0.01% lotion achieved treatment success at the target lesion, with 52.1%, 55.5%, and 58.2% achieving ≥2-grade reduction in erythema, plaque elevation, and scaling severity on the leg, compared with 15.7%, 22.9% and 22.2% of those treated with vehicle, respectively (p<0.001 all; figure 1) figure 1: treatment successa in psoriasis signs of (a) erythema, (b) plaque elevation, and (c) scaling 0% 30% 20% 10% 40% 50% 60% 70% study visit (weeks) p e rc e n ta g e o f p a rt ic ip a n ts 0 2 4 6 8 a. erythema halobetasol propionate 0.01% lotion (n=151) vehicle (n=83) 0% 30% 20% 10% 40% 50% 60% 70% study visit (weeks) p e rc e n ta g e o f p a rt ic ip a n ts 0 2 4 6 8 b. plaque elevation halobetasol propionate 0.01% lotion (n=151) vehicle (n=83) 0% 30% 20% 10% 40% 50% 60% 70% study visit (weeks) p e rc e n ta g e o f p a rt ic ip a n ts 0 2 4 6 8 c. scaling halobetasol propionate 0.01% lotion (n=151) vehicle (n=83) *p<0.01 versus vehicle; **p<0.001 versus vehicle. adefined as a ≥2-grade improvement from baseline in each individual sign of psoriasis (erythema, plaque elevation, and scaling) at the target lesion (leg). ◾ figure 2 illustrates treatment success with hp 0.01% lotion in the leg target lesion figure 2: improvement of psoriasis with once-daily halobetasol propionate 0.01% lotion ◾ overall treatment success per iga was achieved in 37.1% of participants treated with hp 0.01% lotion compared with 8.4% treated with vehicle (p<0.001; figure 3) figure 3: overall treatment successa on iga assessment of disease severity 0% 30% 20% 10% 40% 50% 60% 70% study visit (weeks) p er ce nt ag e o f p ar ti ci p an ts 0 2 4 6 8 halobetasol propionate 0.01% lotion (n=151) vehicle (n=83) **p<0.001 versus vehicle. adefined as a ≥2-grade improvement from baseline in iga score and a score of ‘clear’ or ‘almost clear’ [0 or 1]. iga, investigator global assessment. ◾ hp-treated patients had a 34.2% mean reduction from baseline in overall bsa compared with a 3.7% reduction in vehicle-treated patients (p<0.001; figure 4) figure 4: mean percent reduction in overall body surface area (bsa) -50% -20% -30% -40% -10% 0% 10% study visit (weeks) p er ce nt r ed uc ti o n fr o m b as el in e 0 2 4 6 8 halobetasol propionate 0.01% lotion (n=151) vehicle (n=83) **p≤0.001 versus vehicle. ◾ mean percent reduction from baseline to week 8 in igaxbsa score was also significantly greater with hp treatment (-50.5%) than with vehicle (-13.8%; p<0.001) ◾ a clinically meaningful effect in overall psoriasis treatment (igaxbsa-75) was achieved by 37.7% of participants treated with hp 0.01% lotion compared with 7.2% treated with vehicle (p<0.001; figure 5) figure 5: achievement of ≥50% (igaxbsa-50) and ≥75% (igaxbsa-75) reduction in igaxbsa by week 8 0% 30% 20% 10% 40% 50% 60% halobetasol propionate 0.01% lotion p er ce nt ag e o f p ar ti ci p an ts vehicle igaxbsa-50 igaxbsa-75 **p≤0.001 versus vehicle. bsa, body surface area; iga, investigator global assessment. ◾ a clinically relevant improvement in qol was achieved by week 4 with hp treatment (dlqi mean change of -4.5 vs -3.3; p=0.003) and was maintained at week 8 (dlqi mean change of -5.5 vs -3.8; p<0.001 vs vehicle) conclusion ◾ halobetasol propionate 0.01% lotion provided significant efficacy versus vehicle and clinically relevant improvements in qol following 8 weeks of therapy in patients where the leg was identified as the target lesion references 1. nestle fo, et al. n engl j med. 2009;361(5):496-509. 2. lam lh and sugarman jl. j drugs dermatol. 2016;15(8):945-948. 3. blauvet a, et al. j dermatolog treat. 2018;29(3):220-229. 4. armstrong aw, et al. am j clin dermatol. 2016;17:691-699. 5. sugarman jl, et al. cutis. 2019;103(2):11-116. 6. green lj, et al. j drugs dermatol. 2018;17(10):1062-1069. 7. bernhard j, et al. j am acad dermatol. 1991;25:1170-1174. author disclosures dr. neal bhatia has received honoraria from ferndale laboratories, inc., promius pharma, llc, novartis, allergan, biofrontera ag, intraderm pharmaceuticals, almirall, sun pharmaceutical industries, la roche-posay, mayne pharma group, ortho dermatologics, pierre fabre dermo-cosmétique us, isdin, galderma laboratories, skinfix, inc., and grants/research funding from aclaris therapeutics, inc., asana biosciences, llc, crown laboratories, inc., leo pharma us, dusa pharmaceuticals, inc., menlo therapeutics, par pharmaceutical, pfizer inc., perrigo company, realm therapeutics, sienna biopharmaceuticals, sol-gel technologies, soligenix, inc., strata skin sciences, vidac pharma, brickell biotech, inc., dermira, glenmark generics inc., sanofi/regeneron, actavis, biopharmx, foamix, cutanea life sciences, mc2 therapeutics, ucb, abbvie, atacama therapeutics, naked biome inc., kiniksa pharmaceuticals, ltd., bms, dr. reddy, and vypome (pending). dr. tracey c vlahovic has served as investigator for ortho dermatologics. dr. lawrence green has served as consultant, speaker, and/or investigator for almirall, cassiopea, ortho dermatologics, sol gel, and sun pharmaceuticals. ms. gina martin is an employee of bausch health americas, inc. dr. tina lin is an employee of ortho dermatologics. baseline week 2 week 4 week 6 week 8 efficacy and safety by body weight decile in patients treated with tildrakizumab 100 mg for 28 weeks: pooled data analysis of resurface 1 and resurface 2 alan m menter1, zoe draelos2, jayme heim3, ranga gogineni4, christopher em griffiths5 1division of dermatology, baylor scott & white, and texas a&m college of medicine, dallas, tx, usa; 2dermatology consulting services, high point, nc, usa; 3west michigan dermatology, grandville, mi, usa; 4sun pharmaceutical industries, inc., princeton, nj, usa; 5centre for dermatology research, the university of manchester, manchester, uk introduction • higher body weight is associated with reduced efficacy of some biological therapies in patients with psoriasis1 • tildrakizumab is an anti–interleukin-23 p19 monoclonal antibody approved for the treatment of patients with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy2 • to provide clarity regarding the efficacy and safety of tildrakizumab in relation to body weight, we analyzed efficacy and safety at the decile level objective • to evaluate the efficacy and safety of tildrakizumab across weight deciles up to week 28 using pooled data from the two randomized, placebo-controlled, phase 3 trials (resurface 1 [nct01722331] and resurface 2 [nct01729754])3 methods study design and population • data were pooled from the phase 3 resurface 1 (nct01722331) and resurface 2 (nct01729754) trials and stratified by body weight decile (table 1) • patients with moderate-to-severe plaque psoriasis received tildrakizumab 100 mg at week 0, 4, and every 12 weeks thereafter through week 28 (n = 616) or placebo through week 12 (n = 309) assessments • efficacy was assessed from proportions of patients with psoriasis area and severity index (pasi) 75/90/100 response, absolute pasi score <5/<4/<3/<2/<1, physician global assessment (pga) score of 0 or 1 (0/1), and dermatology life quality index (dlqi) 0/1 • safety was assessed from treatment-emergent adverse events (teaes) and severe aes (saes) statistical analysis • efficacy was analyzed in the full analysis set population (all patients remaining on the same treatment from baseline through week 28, or the end of their participation if they discontinued prior to week 28) • safety was assessed in all patients, as treated • missing data were handled using nonresponder imputation results patient demographics • across weight deciles, 80.6%–96.8% of patients completed the study • baseline weight, body mass index, and disease characteristics were consistent between tildrakizumaband placebo-treated patients within each weight decile (table 1) table 1. demographics and baseline characteristics by body weight decile tildrakizumab 100 mg (n = 616) weight decile n weight range, kg age, yr weight, kg bmi, kg/m2 pasi pga % bsa dlqi 1 62 40.9–62.2 43.8 (14.5) 55.7 (4.60) 21.1 (2.30) 21.1 (8.39) 3.4 (0.55) 33.9 (20.2) 14.6 (6.53) 2 62 62.3–70.5 45.1 (14.2) 66.8 (2.37) 24.2 (2.41) 20.3 (8.41) 3.3 (0.51) 30.2 (16.7) 14.8 (7.23) 3 62 70.7–75.6 46.0 (14.3) 73.2 (1.53) 25.5 (2.33) 20.8 (9.37) 3.3 (0.54) 33.3 (20.9) 13.7 (6.45) 4 61 75.8–81.5 44.2 (14.7) 78.8 (1.62) 26.6 (2.68) 20.5 (8.16) 3.3 (0.57) 31.9 (18.0) 15.2 (7.68) 5 61 81.6–86.2 45.8 (12.1) 84.0 (1.46) 29.0 (3.09) 19.2 (5.83) 3.3 (0.60) 32.3 (16.4) 14.2 (7.09) 6 61 86.3–91.0 48.2 (12.9) 88.9 (1.33) 29.8 (3.22) 20.0 (7.80) 3.3 (0.54) 32.0 (18.7) 14.6 (7.16) 7 61 91.0–96.5 45.8 (13.2) 93.9 (1.51) 31.4 (3.49) 19.7 (6.53) 3.3 (0.61) 32.9 (18.2) 12.5 (6.43) 8 62 96.6–104.3 46.9 (12.7) 100.0 (2.28) 32.9 (3.52) 19.5 (6.77) 3.4 (0.64) 29.9 (17.0) 13.7 (7.30) 9 62 104.4–119.0 45.1 (12.7) 111.3 (4.41) 36.4 (3.74) 19.5 (6.45) 3.2 (0.47) 29.0 (15.7) 15.8 (7.20) 10 62 119.0–194.7 44.1 (12.6) 136.8 (17.1) 42.9 (7.05) 21.6 (9.04) 3.4 (0.55) 34.1 (18.9) 15.1 (7.22) placebo (n = 309) weight decile n weight range, kg age, yr weight, kg bmi, kg/m2 pasi pga % bsa dlqi 1 31 44.0–61.0 48.7 (13.6) 54.5 (4.52) 21.6 (1.93) 22.5 (8.79) 3.2 (0.50) 35.8 (15.7) 14.3 (6.53) 2 31 61.8–69.2 46.4 (15.7) 66.4 (2.13) 24.5 (2.69) 18.3 (6.24) 3.3 (0.46) 30.7 (17.7) 13.0 (6.44) 3 31 69.5–73.0 44.6 (14.3) 71.3 (1.04) 25.2 (2.01) 20.4 (9.61) 3.4 (0.61) 33.6 (18.2) 12.6 (6.88) 4 31 73.6–80.0 43.0 (14.0) 76.5 (1.86) 26.1 (2.57) 19.6 (6.33) 3.3 (0.51) 32.0 (15.1) 15.2 (7.92) 5 31 80.0–85.7 49.1 (12.8) 82.6 (2.07) 27.8 (2.67) 19.6 (8.41) 3.3 (0.64) 27.9 (16.8) 11.6 (7.21) 6 31 85.8–90.7 47.3 (11.8) 88.3 (1.55) 31.3 (4.83) 20.9 (7.05) 3.2 (0.50) 33.3 (16.3) 12.6 (6.22) 7 31 91.0–96.4 47.9 (12.2) 93.6 (1.66) 31.0 (3.97) 19.1 (7.11) 3.5 (0.68) 28.0 (13.7) 14.6 (6.59) 8 31 96.5–103.3 50.4 (11.5) 99.4 (2.09) 32.4 (3.61) 18.9 (5.78) 3.4 (0.50) 28.9 (16.9) 13.4 (6.57) 9 31 104.0–117.3 46.5 (11.6) 109.3 (4.48) 36.4 (4.59) 17.7 (6.02) 3.2 (0.37) 24.0 (11.5) 13.6 (7.56) 10 30 117.7–180.2 47.6 (11.0) 142.3 (19.3) 45.4 (8.22) 19.5 (6.72) 3.6 (0.68) 29.8 (16.5) 14.7 (9.24) data are presented as mean (sd) unless otherwise indicated. bmi, body mass index; bsa, body surface area; dlqi, dermatology life quality index; pasi, psoriasis area and severity index; pga, physician global assessment; sd, standard deviation; yr, year. efficacy • clinical improvement in patients treated with tildrakizumab vs placebo was observed at week 12 and continued through week 28 across all weight deciles • a slightly greater proportion of patients with pasi 75/90/100 responses and pasi <5/<4/<3/<2/<1 scores was observed in the lower weight deciles at week 12, but the difference among weight deciles decreased by week 28 (figure 1 and 2) • pga 0/1 and dlqi 0/1 rates improved through week 28 in all deciles and were lower only in the highest decile (figure 3 and 4) — pga 0/1 response rate range across weight deciles was 46%–67% at week 12 and 55%–73% at week 28 (figure 3) figure 3. proportion of patients with pga score of 0 or 1 by body weight decile and treatment through week 28 1 2 3 4 5 6 7 8 9 10 0 20 40 60 80 100 decile p ro po rt io n of p at ie nt s w ith p g a 0 /1 (% ) week 12 week 28 til 100 mg week 12 placebo full analysis set. data are shown as %. pga, physician global assessment; til, tildrakizumab. — dlqi 0/1 response rate range across weight deciles was 27%–50% at week 12 and 35%–66% at week 28 (figure 4) figure 4. proportion of patients with dlqi score of 0 or 1 by body weight decile and treatment through week 28 p ro po rt io n of p at ie nt s w ith d lq i 0 /1 (% ) 1 2 3 4 5 6 7 8 9 10 0 20 40 60 80 100 decile week 12 week 28 til 100 mg week 12 placebo full analysis set. data are shown as %. dlqi, dermatology life quality index; til, tildrakizumab. safety • safety profiles were similar across all weight deciles — the most common teaes by body decile (>5% of patients receiving tildrakizumab 100 mg through week 28) were nasopharyngitis, headache, and arthralgia conclusions • efficacy of tildrakizumab 100 mg at week 12 was modestly associated with body weight, but differences in efficacy from the lightest to heaviest weight decile decreased by week 28 references 1) pirro f, et al. clin drug investig. 2021;41(10):917–25. 2) ilumya® (tildrakizumab). full prescribing information; april 2022. 3) reich k, et al. lancet. 2017;390(10091):276–88. acknowledgments we thank the patients for their participation and dr. stephen rozzo for contributions to the study. studies were funded by merck sharp & dohme corp., a subsidiary of merck & co., inc. medical writing and editorial support were provided by elisabetta lauretti, phd, of alphabiocom, llc, and funded by sun pharma. disclosures amm received grants and/or honoraria as a consultant, investigator, and/or speaker for abbvie; abbott labs; amgen; anacor; boehringer ingelheim; celgene; eli lilly; janssen biotech, inc.; leo pharma; merck; novartis; sun pharma; and ucb; and is on an advisory board for abbvie, amgen, boehringer ingelheim, eli lilly, janssen, leo pharma, and sienna. zd received grants as an investigator from merck and sun pharma. jh is a speaker, advisor, and consultant for abbvie, amgen, celgene, eli lilly, janssen, and novartis; an advisor for galderma, mayne, and sanofi regeneron; an advisor and consultant for ortho dermatologic; and a speaker and advisor for sun pharma. rg is an employee of sun pharmaceutical industries, inc. ceg received honoraria as an advisory board member and/or speaker from abbvie, almirall, bristol myers squibb, eli lilly, galderma, janssen, leo, novartis, pfizer, sun pharma, and ucb pharma; and research grants from abbvie, celgene, eli lilly, janssen, leo, novartis, pfizer, and sandoz. figure 1. proportion of patients with pasi 75/90/100 response at a) week 12 and at b) week 28 by body weight decile and treatment a) b) full analysis set. data are shown as %. pasi, psoriasis area and severity index; til, tildrakizumab. figure 2. proportion of patients with pasi <5/<4/<3/<2/<1 score at a) week 12 and at b) week 28 by body weight decile and treatment a) b) full analysis set. data are shown as %. pasi, psoriasis area and severity index; til, tildrakizumab. 1 2 3 4 5 6 7 8 9 10 0 20 40 60 80 100 decile 1 2 3 4 5 6 7 8 9 10 0 20 40 60 80 100 decile p ro po rt io n of p at ie nt s w ith pa s i 7 5/ 90 /1 00 (% ) p ro po rt io n of p at ie nt s w ith pa s i 7 5/ 90 /1 00 (% ) pasi 75 pasi 90 pasi 100 til 100 mg pasi 75 pasi 90 pasi 100 placebo pasi 75 pasi 90 pasi 100 til 100 mg pasi <5 pasi <4 pasi <3 placebo pasi <2 pasi <1 pasi <5 pasi <4 pasi <3 til 100 mg pasi <2 pasi <1 pasi <5 pasi <4 pasi <3 til 100 mg pasi <2 pasi <1 1 2 3 4 5 6 7 8 9 10 0 20 40 60 80 100 decile p ro po rt io n of p at ie nt s w ith pa s i < 5/ <4 /< 3/ <2 /< 1 (% ) 1 2 3 4 5 6 7 8 9 10 0 20 40 60 80 100 decile p ro po rt io n of p at ie nt s w ith pa s i < 5/ <4 /< 3/ <2 /< 1 (% ) hilary baldwin,1 emmy graber,2 richard g. fried,3 evan a rieder,4 julie c. harper,5 andrew f. alexis,6 linda stein gold,7 adelaide hebert,8 james del rosso,9 leon kircik,10 ayman grada,11 siva narayanan,12 volker koscielny,13 ismail kasujee13 1acne treatment and research center, brooklyn, ny;2the dermatology institute of boston and northeastern university, boston, ma; 3yardley dermatology associates, morrisville, pa; 4new york university grossman school of medicine, new york, ny; 5the dermatology and skin care center of birmingham, birmingham, al; 6weill cornell medical college, new york, ny; 7henry ford health system, bloomfield, mi; 8uthealth mcgovern medical school, houston, tx; 9jdr dermatology research/thomas dermatology, las vegas, nv; 10icahn school of medicine, mount sinai, new york, ny; 11department of dermatology, case western reserve university school of medicine, cleveland, oh; 12avant health llc, bethesda, md; 13almirall sa, barcelona, spain. an expert panel questionnaire for assessing patient-reported and caregiver-reported outcomes in acne vulgaris presented at fall clinical dermatology conference, 2022 – october 19-23, 2022 – las vegas, nv • acne vulgaris, hereinafter referred to as acne, affects up to 50 million americans and is the most common skin condition in the united states (us). 1 • patients with acne report more effects on their functioning, emotions, and symptoms, related to their skin condition, than do patients with isolated benign skin lesions or those in the normative sample. 2 • acne has been shown to negatively affect patient functioning, emotions, and overall qol. acne has considerable psychosocial impact on patients causing significant negative effects on self-image, leading to feelings of isolation and loneliness, and a significantly lower self-attitude, sense of pride, self-worth, and body satisfaction, and increased feeling of uselessness. 3-5 • current existing patient-reported outcome (pro) instruments does not adequately assess acne impact on patients. background 1. bickers dr, lim hw, margolis d, et al. j am acad dermatol. 2006; 55:490-500; 2. lasek rj, chren mm. arch dermatol. 1998; 134: 454-8; 3. timms rm. psychol health med. 2013; 18(3):310–320; 4. revol o, milliez n, gerard d. br j dermatol. 2015; 172(suppl 1):52–58; 5. gieler u et al. jeadv. 2015; 29 (suppl. 4):12–14; 6. seite s et al. clin cosmet investig dermatol. 2012; 5:123–128; 7. lafrance, m., carey, r. s. body & society. 2018; 24(1-2), 55-87. references conclusions the newly developed epq represents a critical contribution to literature to elicit patient-centric, acne-specific symptoms, impact, and outcomes from acne patients and their caregivers and help improve acne patient management and health outcomes. table 1. expect panel deliberations on epq domain concept question edits from round 2 finalized epq emotional functioning angry 1 changed from “how often did you feel” to “how often has your acne made you feel” over the last 7 days, how often has your acne made you feel angry (mad/sad)? (1-5; never – all of the time) hopelessness about skin 2 changed from “the future of your acne” to “how long will your acne will last and how bad it will get” how worried are you about how long your acne will last and how bad it will get? (1-5; not at all – extremely) 3 no change. how often do you think about your acne? (1-5; never – all of the time) 4 new question added. over the past 7 days, how worried have you been about your acne? (1-5; not at all – extremely) social functioning social media 5 changed from “are you likely to alter or manipulate” to “do you change, edit, or filter” how often do you change, edit, or filter your social media photo or selfie because of your acne? (1-5; never – all of the time) interpersonal relationships 6 added more examples of “real-life” plans. how often does acne impact your “real-life” plans (irl) (like dating or social engagements, playing sports, swimming, hanging out)? (1-5; never – all of the time) 7 changed from “to conceal your acne (e.g., makeup, concealer, camouflage)?” to “hide your acne (like mess with, squeeze/pop, or use makeup, concealer, hairstyle, clothes to cover up)?” how often are you doing something to hide your acne (like mess with, squeeze/pop, or use makeup, concealer, hairstyle, clothes to cover up)? (1-5; never – all of the time) activities of daily living school/work 8 clarified definition of “judged”. “picked on”. how often do you feel picked on or judged because of your acne? (1-5; never – all of the time) 9 changed from “are you concerned about your ability to accomplish your future goals and reach your potential due to your acne?” how concerned are you that your acne will affect your ability to reach your future goals (in school and work) and be the best you can be? (1-5; not at all – extremely) parent interaction 10 no change. do you feel your parents understand your acne-related concerns? (1-5; never – all of the time) sleep 11 added “worrying about, or discomfort (itching/hurting) from your acne”. over the last 7 days, how often has worrying about, or discomfort (itching/hurting) from your acne affected your sleep? (1-5; never – all of the time) perspectives of parents/ caregivers perspectives, concerns 12 changed from “have you been more or less worried” to “how worried have you been”. over the past 7 days, how worried have you been about your child’s acne? (1-5; not at all – extremely) 13 no change. overall, how is your child’s acne right now? [note: ask these questions of both the child and the parent to look for asynchrony] – covered in asis for patient. 5-point adjectival scale (1-5; severe clear) 14 no change. how concerned are you about your child using antibiotics for acne? (1-5; not at all – extremely) (ask at baseline and week 12) 15 new question added. how concerned are you about antibiotic resistance (1-5; not at all – extremely) (ask at baseline and week 12) 16 changed from “are you concerned about” to “how concerned are you about”. how concerned are you about your child’s ability to accomplish future goals and reach full potential due to acne? (1-5; not at all – extremely) (consistently use 5 points) 17 new question added. do you feel that you understand your child’s acne-related concerns? (1-5; never – all of the time) results objective • to create an expert panel questionnaire (epq) comprising of acnespecific pros measures and caregiver-reported measures for use in research studies to fully capture adult and pediatric patient experience and disease impact. methods • a 10-person consensus panel of 8 dermatologists with expertise in the treatment of acne, including pediatric and skin of color focused expertise, one dermatologist /clinical psychologist, and one dermatologist/ psychiatrist was virtually convened using a three-step modified delphi method to establish consensus on epq items that relate to how acne impacts the patient’s emotional functioning, social functioning, activities of daily living. • in the first round, targeted literature reviews were used to identify over 50 pro items for epq by a subgroup of panelists and narrowed epq to 11 items to complement validated asis questionnaire and was identified as an optimal tool to use in community-based real world research involving acne patients. • in second round, 11 epq items were distributed to panel for discussion and solicit comments individually and as a group. • in third round, refined epq items were distributed for feedback and approval. results • panel discussed 11 pros encompassing emotional functioning (angry/mad/sad (1), hopelessness/worries about skin (3)), social functioning (social media activities (1), impact on real-life plans (1), efforts to hide av (1)), and activities of daily living (picked/judged (1), ability to reach future goals (1), parent understanding of av concerns (1), sleep impact (1)). • these recommendations were aligned with literature depicting the issues impacting acne patients. 6,7 • panel suggested wording changes to specific pro measures (table 1). • panel also discussed select questions to parents/caregivers regarding their perspectives of the pediatric patients’ ak and its impact (table 1; items 12-17). • following refinement of epq items, panel unanimously (100%) achieved consensus in approving each of the epq items. sponsored by almirall, s.a. powerpoint presentation • in figure 2 comparison of bdp recovery is made by drug deposition retrieved from individual tape strips representing progressive skin depth through sc and epidermis. • higher amounts of bdp were generally deposited through the skin layers from cal/bdp cream compared to ts, and as expected, most drug was deposited in the upper skin layers (sc) compared to lowers layers (epidermis) after this single application. • the study population included 10 healthy female subjects. • consistently higher amounts of bdp were deposited in the skin following cal/bdp cream application than cal/bdp ts application at 1 hour, 2 hours, 4 hours, and 8 hours. • the values in figure 1 indicate the total bdp recovered from tape strips ( # 3, 5, 7…19) reflecting the total relative amount of drug deposited to sc and epidermis • statistical significance was demonstrated in favour of enhanced drug delivery from cal/bdp cream over cal/bdp ts (p ≤ 0.05) at all time points. • the highest amount of bdp deposited from cal/bdp cream was present at 1 hour after application with continuing detection at slightly lower levels at hours 2, 4, and 8. bdp deposited from cal/bdp ts remained lower and consistent at all time points. • the b17p metabolite was below the lower limit of quantitation in all tested samples. results zoe d. draelos1, matthew m. draelos1, morten praestegaard2 1dermatology consulting services, pllc, high point, north carolina; 2mc2 therapeutics, hørsholm, denmark enhanced skin deposition of betamethasone dipropionate into the skin of human volunteers from calcipotriene/betamethasone dipropionate cream compared to topical suspension • calcipotriene (cal) and betamethasone dipropionate (bdp) cream is an effective and convenient treatment of plaque psoriasis made possible by pad technology™ 1. • pad technology is a novel innovative topical formulation and drug delivery system that allows formulation and efficient topical delivery of challenging molecules, while at the same time maintaining a favourable aesthetic feel of the formulation. • the delivery of topical psoriasis medications into the skin is very important for dermatological efficacy. corticosteroid in combination with calcipotriene is one of the most effective treatments for psoriasis, yet the drug must enter the skin efficiently in order for efficacy to be achieved.4 one way to improve clinical results is to optimize delivery through enhanced vehicles. introduction conclusion • cal/bdp cream is an innovative topical treatment for plaque psoriasis based on pad™ technology. • cal/bdp cream delivered more bdp into the upper (sc) and lower layers (epidermis) of the skin than cal/bdp ts. this may account for the observed difference in efficacy in favour of cal/bdp cream demonstrated in phase iii trials2. • this study confirms pad technology’s benefit in topical delivery in a limited sample size study. • as a limitation, this study was small and included only female subjects objective • the objective of the study was to demonstrate the skin deposition of bdp and its major metabolite betamethasone 17-propionate (b17p), from cal/bdp cream as compared to cal/bdp topical suspension (ts). figure 1. ng bdp recovered from tape strips reflecting compound deposited to stratum corneum and epidermis 1 1 praestegaard et al. dermatology & therapy, 2022. doi: 10.1007/s13555-022-00794-y 2. pinter a, et al. jeadv. 2022;36(2):228-36. 3. wynzora® cream uspi. 4 stein gold et al. j drugs dermatol. 2021 apr 1;20(4):420-425. doi: 10.36849/jdd.2021.5653 references figure 2. comparison of recovery of bdp by hours after application from tape strips representing progressive skin depth through sc and epidermis. cal/bdp cream cal/bdp ts methods • 0.1 ml of cal/bdp cream and cal/bdp ts were applied once to four one-inch squares on the forearms of human female volunteers. one one-inch square on each arm served as control with no product applied. • at 1 hour, 2 hours, 4 hours, and 8 hours after application, tape strips were applied to the application site and held in place for 10 seconds. the first two tape strips removed were discarded to avoid confounding the analysis with residual cream on the skin. this procedure was repeated 20 times on the same area to allow sampling of the stratum corneum (sc) and epidermis down to the level where punctate bleeding occurred indicating intrusion into the dermis. the control square was processed only at 1 hour after application • liquid chromatography–mass spectrometry (lcms) was used to determine the amount of bdp and the metabolite b17p present. only the odd-numbered tape strips (# 3, 5, 7…19) were analyzed while the even-numbered tape strips (#4, 6, 8…20) were saved as backups. • a t-test was used to analyze the paired data with statistical significance defined as p≤0.05. 0 2000 4000 6000 8000 10000 12000 14000 1 2 4 8 n g r e c o v e re d b d p hour **** ** **** * cal/bdp cream cal/bdp ts stars denote a statistical significant difference between cal/bdp cream and ts: *:p<0.05; **: p<0.01; ****:p<0.0001 skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 896 brief article beware of the “blue nevus”: a case report shivani thacker, ba1, mincy chakkalakal, ms2, zachary goldstein, md3, kenneth dale macknet, md3,4 1 western university of health sciences, pomona, ca 2 boston university graduate medical sciences, boston, ma 3 california skin institute, san jose, ca 4 loma linda university, loma linda, ca despite its increased awareness in the last 40 years, clinical diagnostic accuracy of malignant melanoma remains a challenge, especially as it may resemble benign lesions including seborrheic keratoses, intradermal nevi, speckled lentiginous nevi, and blue nevi.1 in this report, we highlight this issue as we present a case of malignant melanoma that was initially treated as seborrheic keratosis, with subsequent presentation resembling a blue nevus. in doing so, we hope to emphasize the significance of clinical history in avoiding this potential pitfall while elaborating on the role of histological examination in making this distinction. a 78-year-old female patient presented with a 6 mm, oval-shaped, blue-black macule on her right anterior upper arm (figure 1) suggestive of the diagnosis of a blue nevus. discussion with the patient revealed that the lesion was previously treated with cryotherapy by another provider in the past year and documented as an irritated seborrheic keratosis. the patient presented six months after cryotherapy noting the lesion had returned and had changed in morphology. the remainder of her physical exam was negative, with no evidence of lymphadenopathy or visceromegaly. she denied any other history of trauma or blistering sunburn to the area. a punch biopsy was performed with a differential diagnosis of blue nevus versus melanoma. histopathological examination revealed a dermal mass of melanophages abstract we report a case of a malignant melanoma clinically mimicking a blue nevus. the patient presented for evaluation of a “seborrheic keratosis” status post cryotherapy that clinically resembled a blue nevus albeit with concerning clinical course prompting biopsy. histopathologic examination revealed malignant melanoma in association with a melanocytic nevus to include areas resembling tumoral melanosis which likely contributed to clinical presentation. we conclude this report with a brief review on the topic of melanoma masquerading as benign lesions (e.g., blue nevus), underscoring the importance of clinical history and histological examination in the evaluation of this entity. introduction case report skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 897 figure 1. clinical examination revealed a 6mm, oval-shaped, blue-black macule on the upper arm suggestive of a blue nevus. figure 2. 20x, a dermal mass of melanophages characteristic of tumoral melanosis is present in this field of view. skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 898 figure 3. 20x, a contrast between the melanoma and melanocytic nevus is evident, with the former demonstrating prominent cytological atypia and pleomorphism. provided insert shows higher power view (40x) of area outlined in red, with mitosis indicated by red asterisk (*). figure 4. 10x, prame immunohistochemistry: the melanoma demonstrates diffuse nuclear positivity with notable absence of staining of melanocytic nevus. skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 899 characteristic of tumoral melanosis (figure 2), which likely contributed to clinical presentation. further examination revealed a significantly atypical melanocytic proliferation juxtaposed to a banal appearing proliferation of melanocytes (figure 3), with prame immunohistochemistry demonstrating diffuse nuclear positivity in the atypical melanocytic proliferation only (figure 4). a diagnosis of malignant melanoma in association with a melanocytic nevus was made and the lesion was excised completely at a subsequent visit. blue nevi encompass a range of congenital and acquired dermal dendritic melanocytic proliferations that exhibit complex clinical and histopathologic features. the lesions emerge as a singular, well-demarcated macule, papule or plaque that is oval or round in shape.2 blue nevi appear blue, gray, blueblack, or black in color due the absorption of longer wavelengths by melanin in the dermis and the reflection of shorter wavelengths of blue light through a phenomenon known as the tyndall effect.3 lesions typically occur in the scalp, buttocks, and dorsal aspects of the extremities. however, they have been reported in the oral and nasal mucosa and other unique locations including the esophagus, bronchus, cervix, endometrium, vagina, penis, prostate, and lymph nodes.3,4,5 a potential pitfall to the diagnosis of blue nevus is the fact that malignant melanoma can be a clinical mimic – especially in the setting of tumoral melanosis as was observed in the current case – and location of the lesion, clinical duration, and history of melanoma can help clinicians discern between the two.1,7 malignant melanoma can masquerade as other lesions as well. eads et al reviewed 577 excised lesions clinically diagnosed as seborrheic keratoses and 37 were proved to be malignant tumors.8 while our patient’s lesion clinically resembled a blue nevus at time of presentation, the possibility that this malignant melanoma was masquerading as a seborrheic keratosis prior to cryotherapy cannot be fully excluded. this case serves to reinforce that a low level of clinical suspicion is needed for further examination to include histopathologic evaluation. moreover, physicians must carefully utilize the patient’s medical history, histopathologic, and immunochemical results when making an accurate diagnosis with unusual dermatologic presentations. this case is a cautionary tale to beware of the “blue nevus” as a potentially devastating diagnostic pitfall was avoided through thorough patient history review and maintaining a low threshold to biopsy a clinically suspicious lesion. this case also emphasizes the significance of screening for the possibility of prior procedure or trauma as it may distort the clinical picture as observed in the current case. as this paper illustrates, many challenges exist in the clinical diagnostic accuracy of malignant melanoma, reaffirming the importance of history and physical examination, as well as the role of histological examination in the evaluation of these difficult lesions. conflict of interest disclosures: none funding: none corresponding author: dale macknet, md california skin institute phone: (909) 645-4508 e-mail: drdmacknet@caskin.com references: 1. grant-kels jm, bason et, grin cm. the misdiagnosis of malignant melanoma. j am acad discussion conclusion skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 900 dermatol. 1999 apr;40(4):539-48. doi:10.1016/s0190-9622(99)70435-4. 2. cabral es, chen fw, egbert bm, swetter sm. acquired blue nevi in older individuals: retrospective case series from a veterans affairs population, 1991 to 2013. jama dermatol. 2014;150(8):873–876. doi:10.1001/jamadermatol.2013.7366 3. murali r, mccarthy sw, scolyer ra. blue nevi and related lesions: a review highlighting atypical and newly described variants, distinguishing features and diagnostic pitfalls. adv anat pathol. 2009 nov;16(6):365-82. doi: 10.1097/pap.0b013e3181bb6b53. 4. artur zembowicz, pushkar a phadke; blue nevi and variants: an update. arch pathol lab med 1 march 2011; 135 (3): 327–336. doi: 10.5858/2009-0733-ra.1 5. sun j, morton th jr, gown am. antibody hmb45 identifies the cells of blue nevi. an immunohistochemical study on paraffin sections. am j surg pathol. 1990 aug;14(8):748-51. doi: 10.1097/00000478-199008000-00006. 6. loghavi, s., curry, j., torres-cabala, c. et al. melanoma arising in association with blue nevus: a clinical and pathologic study of 24 cases and comprehensive review of the literature. mod pathol 27, 1468–1478 (2014). https://doi.org/10.1038/modpathol.2014.62 7. bari o, cohen pr. tumoral melanosis associated with pembrolizumab-treated metastatic melanoma. cureus. 2017 feb 13;9(2):e1026. doi: 10.7759/cureus.1026. 8. eads tj, hood af, chuang ty, faust hb, farmer er. the diagnostic yield of histologic examination of seborrheic keratoses. arch dermatol. 1997 nov;133(11):1417-20. https://doi.org/10.5858/2009-0733-ra.1 lilly immunology winter clinical dermatology conference; hawaii, usa; january 13-18, 2023 key resultsbackground ■ patients with moderate-to-severe atopic dermatitis (ad) commonly experience worsening of disease severity (flares), often requiring acute treatment with topical corticosteroids (tcs) or other rescue medication. ■ atopic dermatitis is an il-13 dominant disease.1 lebrikizumab targets and potently neutralizes il-13 signaling with high binding affinity to a specific epitope with a slow off-rate.2,3 ■ lebrikizumab achieved primary and all key secondary endpoints at week 4 and week 16 in 2 randomized, double-blind, placebo-controlled, phase 3 clinical trials in adults and adolescents with moderate-to-severe ad; advocate 1 (nct04146363) and advocate 2 (nct04178967).4 – significant improvements vs placebo were seen as early as week 2 for eczema area and severity index (easi)-75 and for ≥4-point improvement in pruritus numeric rating scale (nrs) in advocate 1. summary methods disclosures  jq del rosso is on the board of directors and president-elect of the american acne and rosacea society. he is a research investigator, consultant, advisor, and/or speaker for abbvie, aclaris, almirall, amgen (celgene), anaptys bio, arcutis, aslan, asthenex, bausch (ortho dermatology), beiersdorf, biofrontera, biopharmx, biorasi, blue creek, boehringer ingelheim, botanix, brickell, cara therapeutics, cassiopea, dermata, dermavant, dermira, eli lilly and company, encore, epi health, evommune, ferndale, galderma, genentech, incyte, janssen, jem health, la roche posay, leo pharma, mc2, mendera, novan, pfizer, ralexar, regeneron, sanofi-genzyme, sente, solgel, sonoma (intraderm), sun pharma, ucb, verrica, and vyne (foamix/menlo). p kwong is an investigator for eli lilly and company and has received consulting and/or speaker fees from abbvie, arcutis, bristol myers squibb, dermavant, eli lilly and company, epi health, galderma, incyte, l’oreal, novan, novartis, ortho, pfizer, regeron/sanofi genzyme, sun pharm, and verrica. i hussain is a speaker for grifols and optinose, and an investigator for abbvie, eli lilly and company, kymab, leo pharma, novartis, pfizer, regeneron, and sanofi. s barbarot is an investigator or speaker for abbvie, almirall, astrazeneca, chiesi, eli lilly and company, janssen, leo pharma, novartis, pfizer, sanofi-genzyme, and ucb pharma. jm carrascosa is an investigator and/or has received consulting fees and/or speaker fees and/or has participated in steering committee from abbvie, almirall, amgen, boehringer ingelheim, bristol myers squibb, eli lilly and company, galderma, janssen, leo pharma, novartis, and regeron/sanofi genzyme. mj rueda, ar atwater, h elmaraghy, l sun, and cr natalie are employees of eli lilly and company. s chen is an employee of tigermed working on behalf of eli lilly and company. s weidinger is a speaker, advisory board member, and/or investigator for abbvie, almirall, eli lilly and company, kymab, leo pharma, novartis, pfizer, regeneron, and sanofi. he has received research grants from la roche posay, pfizer, and sanofi.  this study was previously presented at the international symposium on atopic dermatitis 12th georg rajka international symposium, 2022 abbreviations ad=atopic dermatitis; ae=adverse event; bsa=body surface area; ci=95% confidence interval; dlqi= dermatology life quality index; easi=eczema area and severity index; easi-75=75% reduction from baseline in easi score; eu=european union; fda=us food and drug administration; hr=hazard ratio; iga=investigator’s global assessment, itt=intent-to-treat; ld=loading dose; leb=lebrikizumab; mitt=modified intent-to-treat; nrs=numeric rating scale; pbo=placebo; q2w=every 2 weeks; q4w=every 4 weeks; r=randomization; tcs=topical corticosteroid; us=united states scan or click the qr code or use this url (https://lillyscience.lilly.com/congress/wcdc2023) for a list of all lilly content presented at the congress. other company and product names are trademarks of their respective owners. lebrikizumab monotherapy reduces flares in patients with moderate-to-severe atopic dermatitis james q. del rosso1, pearl kwong2, iftikhar hussain3, sebastien barbarot4, jose manuel carrascosa5, maria jose rueda6, amber reck atwater6, hany elmaraghy6, luna sun6, sherry chen7, chitra r. natalie6, and stephan weidinger8 1jdr dermatology research, las vegas, nv, usa; 2solutions through advanced research, jacksonville, fl, usa; 3vital prospects clinical research institute, tulsa, ok, usa; 4department of dermatology, centre hospitalier universitaire de nantes, nantes, france; 5department of dermatology, hospital universitari germans trias i pujol. igtp, barcelona, spain; 6eli lilly and company, indianapolis, in, usa; 7tigermed, somerset, nj, usa; 8department of dermatology, university hospital schleswig-holstein, kiel, germany references 1. tsoi lc et al. j invest dermatol. 2019; 139:1480-9. 2. ultsch m et al. j mol biol. 2013; 425:1330-9. 3. okragly a, et al. presented at the inflammatory skin disease summit, new york, 2021 4. silverberg j et al. presented at american academy of dermatology (aad), virtual meeting experience, 2022 (through week 16) key eligibility criteria ■ adults ≥18 years old and adolescents (≥12 to <18 years old with weight ≥40 kg) ■ moderate-to-severe ad, defined as: – easi score ≥16 – investigator’s global assessment (iga) score ≥3 – body surface area % involvement ≥10% ■ chronic ad for ≥1 year for whom topical treatment was inadequate or inadvisable ■ dupilumaband tralokinumab-naïve results this study was funded by dermira, a wholly owned subsidiary of eli lilly and company. almirall, s.a. has licensed the rights to develop and commercialize lebrikizumab for the treatment of dermatology indications, including atopic dermatitis, in europe. lilly has exclusive rights for development and commercialization of lebrikizumab in the united states and the rest of the world outside of europe. flare definitions ■ flare was defined 3 ways for these analyses: – per protocol rescue flare: initiation or intensification of rescue therapy with topicals (corticosteroids, calcineurin inhibitors, crisaborole); systemics (corticosteroids, immunosuppressants, biologics, janus kinase inhibitors); phototherapy; or photochemotherapy – high potency tcs/systemic rescue flare: use of topical high potency corticosteroids or systemics (corticosteroids, immunosuppressants, biologics, janus kinase inhibitors); phototherapy; or photochemotherapy – ae flare: an exacerbation of ad, captured as a treatment-emergent adverse eventa objective ■ to assess the ability of lebrikizumab to reduce flares in patients with moderate-to-severe ad through the 16-week initial randomized treatment period in the advocate 1 and advocate 2 phase 3 clinical studies.4 a ad exacerbation was defined using specific medical dictionary for regulatory activities preferred terms of dermatitis atopic, rebound atopic dermatitis, or eczema. ■ during the 16-week induction period, a smaller proportion of patients treated with lebrikizumab versus placebo experienced an ad flare as defined by use of at least one per protocol rescue medication (per protocol flare) in advocate 1 (11.0% vs 33.3% ) and advocate 2 (18.5% vs 39.7%) – the rate ratio for adjusted per protocol flare rate for lebrikizumab versus placebo was 0.34 in advocate 1 and 0.43 in advocate 2 (both p<0.001) ■ fewer patients treated with lebrikizumab vs placebo experienced an ad flare as defined by use of a high potency tcs or systemic rescue medication in advocate 1 (4.2% vs 17.0%) and advocate 2 (11.7% vs 28.8%) ■ fewer patients treated with lebrikizumab versus placebo experienced an ad flare defined as at least one reported teae representing ad exacerbation in advocate 1 (6.0% vs 21.3%) and advocate 2 (10.3% vs 26.9%) conclusions in patients with ad, treatment with lebrikizumab monotherapy resulted in significantly fewer ad flares than treatment with placebo across multiple definitions of ad flare time to first flare: per protocol rescue flare time to first high potency tcs/systemic rescue flare time to first ae flare high potency tcs/systemic rescue flare was defined as use of topical high potency corticosteroids; systemics (corticosteroids, immunosuppressan ts, biologics, janus kinase inhibitors); phototherapy or photochemotherapy ae flare was defined as an exacerbation of ad, captured as a treatmentemergent adverse event study design analysis populations ■ intent-to-treat population (itt; all randomized patients) for advocate 1 and modified itt (mitt) for advocate 2.a ■ for ae flare and exposure adjusted flare rate, the analysis population was the safety population for advocate 1 and the modified safety population for advocate 2. statistical analyses ■ the kaplan-meier product limit method was used to estimate the survival for time to event analyses (eg, time to first flare). ■ the stratified log-rank test was performed with treatment group and covariates (eg, geographic region [us vs eu vs rest of world], age [adolescent patients 12 to <18 vs adults ≥18 years] and baseline disease severity [iga 3 vs 4]) in the model. ■ flare count (considering multiple flares per patient) based on per protocol rescue flare was summarized and adjusted flare rate was estimated by negative binomial regression. ■ nominal p-values are reported without control for multiplicity. data for adjusted flare rate were from negative binomial regression analysis with treatment group, age group, baseline iga, and region as explanatory variables. the natural logarithm of the flare exposure time in weeks was used as an offset variable in the model to adjust for subjects having different exposure times. per protocol rescue flare was defined as initiation or intensification of rescue therapy with topicals (corticosteroids, calcineurin inhibitors, crisaborole); systemics (corticosteroids, immunosuppressants, biologics, janus kinase inhibitors); phototherapy; or photochemotherapy systemic rescue medications included corticosteroids, immunosuppressants, biologics, and janus kinase inhibitors. no patients used crisaborole, phototherapy or photochemotherapy. a hr: stratified by geographic region (us vs eu vs rest of world), age (adolescents vs adults), and disease severity (iga 3 vs 4) b log-rank for comparison with placebo, stratified by geographic region (us vs eu vs rest of world), age (adolescents vs adults), and disease severity (iga 3 vs 4) per protocol rescue flare was defined as initiation or intensification of rescue therapy with topicals (corticosteroids, calcineurin inhibitors, crisaborole); systemics (corticosteroids, immunosuppressants, biologics, janus kinase inhibitors); phototherapy; or photochemotherapy. analysis was based on the itt population (advocate 1) or mitt population (advocate 2). a hr: stratified by geographic region (us vs eu vs rest of world), age (adolescents vs adults), and disease severity (iga 3 vs 4). b log-rank for comparison with placebo, stratified by geographic region (us vs eu vs rest of world), age (adolescents vs adults), and disease severity (iga 3 vs 4). analysis of high potency tcs/systemic rescue flare was based on the itt population (advocate 1) or mitt population (advocate 2). analysis of ae flare was based on the safety population (advocate 1) or modified safety population (advocate 2). note: only data from the 16-week induction period are presented. a leb-treated patients received a 500mg ld at weeks 0 and 2. a in advocate 2, 18 patients were excluded from the itt as they did not meet eligibility criteria of having moderate-to-severe ad. thus the analyses in advocate 2 used the modified itt. statistical methods study was sponsored by eli lilly and company slide number 1 skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 860 original research a randomized controlled study of topical benzoyl peroxide with oral doxycycline versus topical benzoyl peroxide with oral lymecycline in acne vulgaris rekha gurunatham ponnurangam, md(dvl)1, sindhuja ramasamy md(dvl)2, sridhar venu md(dvl)2, jayakalyani vijayananth md(dvl)2 1 department of dermatovenereoleprology, tagore medical college hospital, tamilnadu, india 2 department of dermatovenereoleprology, chengalpattu medical college hospital, tamilnadu, india acne is a very common and unique disease of human beings.1 acne involves the inflammation of the pilosebaceous unit with varied manifestations including comedones, pustules, papules, cysts, nodules, and scarring. 2 tetracyclines are the most common oral antibiotic prescribed for acne vulgaris in patients above 12 years. they are classified as first generation (tetracycline, chlortetracycline, oxytetracycline, and demeclocycline), second generation (doxycycline, lymecycline, meclocycline, methacycline, minocycline, and rolitetracycline) third generation (tigecycline), abstract background: acne vulgaris is a chronic inflammatory disease of the pilosebaceous unit, which has a variable course with acute or insidious onset, relapses, and recurrences. it is one of the most common diseases of patients attending the dermatology clinic. tetracyclines are the most common oral antibiotic prescribed for acne vulgaris. aims: our study aims to compare the efficacy of topical 2.5% benzoyl peroxide gel (bpo) with oral doxycycline versus topical 2.5% benzoyl peroxide gel with oral lymecycline in the treatment of acne vulgaris. methods: the study included 100 patients with acne vulgaris divided into two groups of 50 each. group a was treated with topical 2.5% benzoyl peroxide gel once daily application at night and capsule doxycycline 100mg twice a day and group b was treated with topical 2.5% benzoyl peroxide gel once daily application at night and capsule lymecycline 408 mg once a day for 12 weeks. the primary assessment was done using indian association of acne (iaa) grading at baseline and then every fortnight for 12 weeks. patients were followed up for another 12 weeks after completion of the study. results: the grade wise distribution of acne based on iaa grading between the two groups was compared. chi square test and p-value for all 3 grades of acne at baseline, 2 weeks, 4 weeks, 6 weeks, 8 weeks, 10 weeks, and 12 weeks showed statistical improvement among patients in group b at 2, 8 and 10 weeks with p-values of 0.01,0.01 and 0.007, respectively. conclusions: from our study it is evident that lymecycline is superior to doxycycline, with much statistical significance among moderate to severe acne. introduction skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 861 and fourth generation (azatetracycline, and alkylaminotetracycline. 3, 4 doxycycline, a semi synthetic tetracycline is used in the dose of 100 mg bd for 6-12 weeks. major side effects are phototoxicity, nausea, vomiting, diarrhea, and abdominal pain. lymecycline, a lysinomethyl-tetracycline, water soluble prodrug of tetracycline is approximately 5000 times more soluble than tetracycline and is used in dose of 408mg once daily. it inhibits bacterial ribosomal protein synthesis, has anti-inflammatory & anti-collagenolytic effects, inhibits polymorphonuclear cells and eosinophil chemotaxis, matrix metalloproteinases and pro-inflammatory cytokines: tnf-α, il-1 & il6.5 the major side effects include discoloration of teeth and enamel hypoplasia, delayed bone growth, diarrhea, and nausea and rarely photosensitivity.6 topical benzoyl peroxide is used in acne to reduce resistance and to aid in the anti bacterial effect of oral antibiotics. 7, 8 our study aims to compare the efficacy of topical 2.5% benzoyl peroxide gel (bpo) with oral doxycycline versus topical 2.5% benzoyl peroxide gel with oral lymecycline in the treatment of acne vulgaris. this is a randomized controlled open labeled prospective interventional study conducted over a period of one year from august 2017 to july 2018 at the outpatient department of dermatology at a tertiary center after obtaining institutional ethical committee approval. a total of 100 patients of either sex in age group 14-35 years with clinical diagnosis of acne vulgaris including hormonal acne and drug induced acne were included in the study after obtaining written informed consent. patients who were on topical or systemic anti acne medications in the last 1month, females yet to complete their family, pregnant and lactating females, patients with known hypersensitivity to any of the components of the study medication, history of regional enteritis/ulcerative colitis/antibiotic associated colitis, severe hepatic, renal or photosensitive disease were excluded from the study. those patients who developed severe side effects/intolerance during the treatment, who wanted to discontinue the treatment or if they used any other topical medicated creams, lotions, powders, or solutions other than study medication during the study period were also excluded from the study. during the initial visit, the demographic details such as name, age, sex, marital status, occupation were noted for all the patients in a preformed proforma. history was taken regarding the following details: presenting complaints, the duration of lesions, associated symptoms, any prior treatment history, intake of drugs that can induce acne, treatment for any hormonal disorders, precipitating factors such as sun exposure, premenstrual flare, stress, smoking, sweating, diet, any significant past or personal history, menstrual & obstetric history in females and family history of acne. a thorough clinical examination was done in good lighting. skin type was assessed: oily, dry, or normal type. numbers, morphological types, and distribution of lesions were all noted down in the proforma. we have taken standard photographs at a constant distance and lighting from three angles: right, left, and straight view of face. it was done at baseline and every 2 weeks till the lesions subsided. general examinations including mucocutaneous sites and systemic methods skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 862 examinations were done in all patients. features of hirsutism, if any, were noted. basic laboratory investigations such as complete hemogram, liver function test, renal function test, thyroid profile, urine routine and blood sugar values were done in all cases to rule out comorbidities. patients with polycystic ovarian disease (pcod) as an etiological factor were screened in the department of obstetrics and gynecology and appropriate treatment was instituted. patients were allocated into two groups of 50 each, group a and group b by simple random sampling. 50 patients in group a were treated with topical 2.5% benzoyl peroxide gel once daily application at night and capsule doxycycline 100mg twice a day for 12 weeks. 50 patients in group b were treated with topical 2.5% benzoyl peroxide gel once daily application at night and capsule lymecycline 408mg once a day for 12 weeks. patients were asked to use noncomedogenic sunscreen and to avoid high calorie diet and anabolic steroids. they were informed about the side effects such as photosensitivity, nausea, vomiting, epigastric pain, diarrhea and burning or stinging sensation following gel application. they were asked to report immediately to us if any. the primary assessment parameters were done using indian association of acne (iaa) grading at baseline and then every fortnight till 12 weeks or till the lesion subsided. the secondary efficacy parameters used were physician global assessment score and patient global assessment score at 4 weeks. patients were followed up for another 12 weeks after completion of the study. iaa grading iaa grading is based on lesion counting and morphology. grade 1 – mild acne: comedones <30, papules <10, no scarring grade 2 – moderate acne: comedones any number, papules >10, nodules <3 scarring +/ grade 3 – severe acne: comedones any number, papules any number, nodules/cyst >3, scarring + physician global assessment score: score definition description 0 clear residual hyperpigmentation and erythema may be present 1 almost clear few scattered comedones and papules 2 mild easily recognizable; less than half of face 3 moderate many comedones, papules, pustules. 1 nodule may be present. more than half of face 4 severe covered with comedones, numerous papules and pustules; few nodules and cysts may or may not be present. entire face is involved. physician global assessment is based on a 5-point scale. it was calculated at baseline and 4 weeks. as per us fda a score of clear or almost clear or 2-point scale reduction in acne from the baseline is considered a satisfactory improvement. patient global assessment score was calculated on a 4-point scale at 4 weeks skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 863 among both the groups. the scoring used was: 1 much better 2 slightly better 3same 4 worse. the observations were analyzed using spss (version 17). the difference in reduction of severity of lesions at initial visit and follow up was analyzed using chi – square test. (p < 0.05 is the cut off value for statistical significance). out of 100 patients enrolled in our study, only 91 completed their study and 9 patients (5 from group a and 4 from group b) were lost to follow up and hence excluded from the study analysis. the predominant age in both groups was below 20 years. there was no significant difference between the age distribution in both the groups. in group a, 31 (62%) were female and 19 (38%) were male. in group b, 24(48%) were female and 26 (52%) were male patients. 28 patients in group a and 27 patients in group b were symptomatic. in both the groups pain was the predominant symptom. 4 patients had pcod in group a and 5 in group b. 5 patients in group a and 8 in group b had drug induced acne. in group a, 36 patients had comedones, 38 patients had papules, and 11 patients had pustules, cysts and nodules. among group b, 36 patients had comedones, 38 patients had papules, 22 patients had pustules, 17 patients had cysts and 15 had nodules. the grade wise distribution of acne based upon iaa grading among both the groups were compared. chi square test and p values for all 3 grades of acne at baseline, 2 weeks, 4 weeks, 6 weeks, 8 weeks, 10 weeks, and 12 weeks showed statistical improvement among patients in group b at 2, 8 and 10 weeks with p values of 0.01,0.01 and 0.007 respectively. (table 1) with respect to the physician global assessment score, at 4 weeks, among 45 patients of group a, 10 patients had almost clear, 9 patients had clear, 15 patients had mild, and 11 patients had moderate resolution of lesions. among 46 patients of group b at 4 weeks, 11 patients had almost clear, 20 patients had clear, 4 patients had mild, and 11 patients had moderate resolution of lesions. the comparative result was statistically significant at 4th week p= 0.04 (p <0.05) (figure 1). comparing the patients global assessment score at 4 weeks, among 45 patients of group a, 11 patients gave much better response, 15 patients gave slightly better response, 19 patients didn’t find any improvement. among 46 patients of group b, 19 patients gave much better response, 16 patients gave slightly better response, 11 patients didn’t find any improvement. in both the groups no one experienced a worse response. the result was statistically significant p= 0.03 (p <0.05) (figure 2). during follow up relapse of acne was seen in 17.7% of patients in group a and 10.8% in group b. they were treated with topical benzoyl peroxide alone. in group a, 1 patient had epigastric pain, 4 patients developed hyperpigmentation, 3 patients had photosensitivity, among which 2 developed burning sensation following benzoyl peroxide application and among group b, 2 patients had hyperpigmentation, 1 patient had results skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 864 table 1. indian association of acne (iaa) grade wise comparison iaa baseline 2 weeks group a group b group a group b frequency percent frequency percent frequency percent frequency percent grade 1 15 30 5 10 16 32 4 8 grade 2 14 28 17 34 14 28 15 30 grade 3 21 42 28 56 10 20 12 24 cleared 5 10 15 30 chi sq 5.78 12.53 p 0.06 0.01 iaa 4 weeks 6 weeks group a group b group a group b frequency percent frequency percent frequency percent frequency percent grade 1 13 26 8 16 7 14 8 16 grade 2 10 20 15 30 10 20 3 6 grade 3 1 2 1 2 cleared 16 32 7 14 7 14 13 26 chi sq 8.51 5.64 p-value 0.07 0.13 iaa 8 weeks 10 weeks 12 weeks group a group b group a group b frequency percent frequency percent frequency percent frequency percent grade 1 8 16 4 8 1 2 grade 2 1 2 grade 3 cleared 8 16 11 22 5 10 3 6 chi sq 9.97 9.89 4.17 p-value 0.01 0.007 0.1 skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 865 figure 1. physician global assessment score. figure 2. patient global assessment score. figure 3. adverse effects. skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 866 diarrhea which settled after probiotic supplementation (figure 3). acne vulgaris is a chronic inflammatory disease of the pilosebaceous unit and has a variable course with acute or insidious onset, relapses, and recurrences. there are many studies comparing various tetracyclines in the treatment of acne, but hardly any studies that compare lymecycline with doxycycline from. this is one such study wherein we have compared the efficacy of one of the commonly used tetracyclines, doxycycline with the newer lymecycline. the demographic details obtained from our study from both the groups of totally 100 patients were compared and were found to be similar. in our study the predominant age group was <20 years with 56% in both the groups. among the patients enrolled in our study females were predominant with 55% and males were 45%. symptomatic acne with itching, pain or both was 55%. 9% of the patients (4% in group a and 5% in group b) had associated pcod and underwent hormonal therapy for the same. 10% had drug induced acneiform eruptions. 32% of the patients had a positive family history of acne among siblings and parents. the major morphological pattern of lesion was papules followed by comedones, pustules, nodules, and cyst. based upon iaa grading significant statistical improvement was seen among patients in group b (lymecycline group) at 2, 8 and 10 weeks with the reduction in both the number and severity of acne (p <0.05). in group b patients there was a rapid initiation of improvement among the severe grades of acne (grade 3 & 4) (figure 4), where it proved to give results within 8 weeks whereas it took longer time of about 12 weeks in group a. in the less severe grades (grade 1 & 2), both drugs showed similar efficacy. hence lymecycline can be considered as a first choice of oral antibiotic when treating moderate to severe inflammatory acne. papulopustular lesions resolution needed about 8 weeks of lymecycline therapy, since lymecycline works at all ph and it took 12 weeks with the doxycycline therapy (figure 5). to avoid emergence of antibiotic resistance, monotherapy was avoided and combination with topical 2.5% benzoyl peroxide was given. this was comparable to a study by bossyut et al. where among 136 patients, at week 12, the mean percent reduction in inflammatory count was 63% and total lesions counts was 58% for lymecycline. the median percent reduction in non-inflammatory count was 54% for lymecycline. 87% of all patients tolerated the treatments well. results showed that lymecycline has a comparable efficacy and safety profile.9 lymecycline gave satisfactory results in patients with pcod associated severe acne in a period of 8 weeks as compared to 12 weeks in group a. truncal acne was slower to respond than facial acne which showed response only after at least 8 weeks of treatment. among the 45 patients of group a, 22% (10 patients) experienced side effects with 8.8% having hyperpigmentation at their acne site, 6.6% with symptoms of photosensitivity, 2.2% with epigastric pain. 4.4% developed burning sensation after benzoyl peroxide application. among the 46 patients of group b, only 6.5% experienced side effects with 4.5% having discussion skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 867 figure 4. patient in lymecycline group over 6 weeks. figure 5. patient in doxycycline group over 10 weeks. skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 868 hyperpigmentation at their acne site, 2.7% had diarrhoea which resolved within a week with probiotics and the drug was continued in that patient. no patient developed symptoms of photosensitivity. hence it is a drug with very low side effect profile compared to doxycycline. the side effect profile of lymecycline was much better than that of doxycycline and none of our patients had phototoxic reactions which is one of the added advantages for its use in a tropical country. this was also shown in a study by bjellerup m et al where it was concluded that doxycycline has a higher phototoxic potency than lymecycline.10 from our study it is evident that lymecycline is superior to doxycycline, with much statistical significance among moderate to severe acne. there was earlier reduction in lesions and the duration of therapy needed was also less than that needed for doxycycline. but there was not much significant difference in mild forms of acne. the major advantages of lymecycline are its once daily dosing which led to improved compliance and better patient satisfaction and the lack of photosensitivity which is advantageous in a tropical country like india. conflict of interest disclosures: none funding: none corresponding author: rekha gurunatham ponnurangam md(dvl) assistant professor department of dermatovenereoleprology, tagore medical college hospital, rathinamangalam, chennai-600127, tamilnadu-india. email: sweetgalrekha@gmail.com references: 1. stern s. dermatologists and office‐based care of dermatologist disease in the 21st century. j invest dermatol symp proc 2004; 9: 126–30. 2. cooper aj, harris vr. modern management of acne. med j aust. 2017 jan 16;206(1):41-45 3. agwuh kn, macgowan a. pharmacokinetics and pharmacodynamics of the tetracyclines including glycylcyclines. j antimicrob chemother. 2006; 58(2):256–265. 4. saleha t, syed faheem a r, ummar a. tetracycline: classification, structure activity relationship and mechanism of action as a theranostic agent for infectious lesions-a mini review. biomed j sci&tech res 7(2) 2018. bjstr. ms.id.001475. 5. pubchem [internet]. bethesda (md): national library of medicine (us), national center for biotechnology information; 2004-. pubchem compound summary for cid 54707177, lymecycline; available from: https://pubchem.ncbi.nlm.nih.gov/compound/lym ecycline 6. dubertret l, alirezai m, rostain g, lahfa m, forsea d, niculae bd, simola m, horvath a, mizzi f. the use of lymecycline in the treatment of moderate to severe acne vulgaris: a comparison of the efficacy and safety of two dosing regimens. eur j dermatol. 2003 jan-feb; 13(1):44-8. 7. williams hc, dellavalle rp, garner s. acne vulgaris. lancet. 2012 jan 28; 379(9813):361-72. doi: 10.1016/s0140-6736(11)60321-8. epub 2011 aug 29. erratum in: lancet. 2012 jan 28; 379(9813):314. 8. dutil m. benzoyl peroxide: enhancing antibiotic efficacy in acne management. skin therapy lett. 2010 nov-dec; 15(10):5-7. 9. bossuyt l, bosschaert j, richert b et al. lymecycline in the treatment of acne: an efficacious, safe and cost-effective alternative to minocycline. eur j dermatol. 2003; 13(2):130– 135. 10. m. bjellerup, b. ljunggren. differences in phototoxic potency: a study on doxycycline and lymecycline in human volunteers, using an objective method for recording erythema. br j dermatol. 1994 mar; 130 (3):356-60. conclusion https://pubchem.ncbi.nlm.nih.gov/compound/lymecycline https://pubchem.ncbi.nlm.nih.gov/compound/lymecycline https://onlinelibrary.wiley.com/action/dosearch?contribauthorraw=bjellerup%2c+m https://onlinelibrary.wiley.com/action/dosearch?contribauthorraw=ljunggren%2c+b clinical responses in patients with moderate-to-severe plaque psoriasis following withdrawal and re-treatment with risankizumab or switching from ustekinumab to risankizumab kim a papp,1 andrew blauvelt,2 mary flack,3 yihua gu,4 elizabeth h z thompson5 1k papp clinical research and probity medical research, waterloo, on, canada; 2oregon medical research center, portland, or, usa; 3boehringer ingelheim pharmaceuticals inc., ridgefield, ct, usa; 4abbvie inc., north chicago, il, usa; 5abbvie inc., redwood city, ca, usa 1. papp ka, et al. n engl j med 2017; 376: 1551-60. • to assess the efficacy following drug withdrawal and re-treatment with risankizumab or switching from ustekinumab to risankizumab at week 24 of the open label extension (ole). • switching treatment to risankizumab in patients initially treated with ustekinumab resulted in higher clinical responses, as measured by increases in pasi and spga responses at 24 weeks. • re-treatment with two doses (ole baseline and week 12) of 90 mg of risankizumab following risankizumab withdrawal also resulted in return of substantial clinical benefit. • the rates of adverse events through 24 weeks of ole were as expected for the population and similar to those observed in the parent study. • risankizumab is a humanized igg1 monoclonal antibody that inhibits il-23 by binding its p19 subunit. • in a phase 2 trial, risankizumab demonstrated superiority over ustekinumab in patients with moderate-to-severe plaque psoriasis. study design and patients • in the phase 2 (“parent”) study,1 166 patients with moderate-tosevere plaque psoriasis were randomized to receive subcutaneous injections of risankizumab (18 mg single dose at week 0, or 90 or 180 mg at weeks 0, 4, and 16) or ustekinumab (45 or 90 mg, based on body weight at weeks 0, 4, and 16). • patients were followed up through week 48 during the double-blind period. • patients (n=110) who completed 48 weeks in the parent study or who failed to achieve 50% improvement in psoriasis area and severity index (pasi 50) response between weeks 24 and 48 were eligible to enter the ole (figure 1). • in this ongoing ole, all patients received 90 mg risankizumab at baseline and every 12 weeks thereafter, regardless of their response level at the end of the parent study. • patients who failed to achieve pasi 90 responses in the ole could increase their dose to 180 mg risankizumab starting at week 12; however, all patients received 90 mg risankizumab for the study period reported here. efficacy and safety analyses • in this preliminary analysis, data through week 24 of the ole from all entering patients were included. • the following efficacy endpoints were assessed at week 24 of ole: – pasi 90, 90% improvement in psoriasis area and severity index – pasi 100, 100% improvement in psoriasis area and severity index – spga 0/1, static physician global assessment score of clear or almost clear – spga 0, static physician global assessment score of clear • non-responder imputation (nri) was used for missing efficacy data. • treatment-emergent adverse events (teae) were defined as any adverse events occurring after the first dose of the study drug in the ole through 24 weeks of ole and within 105 days after the last dose of study drug (if the patient discontinued treatment during ole). figure 1. study design of phase 2 trial of risankizumab in psoriasis patients 16week 0 4 12 4824 = dose r a n d o m is e d 1 :1 :1 :1 risankizumab 18 mg s.c. a n=40 ustekinumab 45/90 mg s.c. b n=43 risankizumab 180 mg s.c. n=41 risankizumab 90 mg s.c. n=42 1 o endpoint: pasi 90 at week 12 16week 0 12 24 ole week 24: e cacy and safety n=22 n=28 n=33 n=27 // // // // risankizumab 90 mg s.c. d double-blind period (n=166) open-label extension (n=110) follow-up c a. placebo only at weeks 4 and 16. b. used as per label (45 mg or 90 mg in patients with body weight ≤100 kg or >100 kg at randomization, respectively). c. patients completing week 48 of the “parent” study (nct02054481) were eligible to enroll in the ole (nct02203851). patients who failed to achieve at least 50% improvement from baseline in pasi (<pasi 50) during the followup period (indicated by gray shading) were eligible to enter the ole without completing the “parent” study. d. patients who failed to achieve pasi 90 response in the ole could increase their dose to 180 mg risankizumab starting at week 12; however, all patients received 90 mg risankizumab for the study period reported here. abbreviations: ole=open-label extension; pasi=psoriasis area and severity index; s.c.=subcutaneous. • of the 166 patients randomized in the phase 2 (“parent”) study, 110 (66.3%) patients enrolled in the ole and received 90 mg risankizumab (figure 1). efficacy • at ole entry, pasi 90 response rates for patients previously treated with 18 mg, 90 mg, or 180 mg risankizumab or ustekinumab were 0% (0/22), 53.6% (15/28), 51.5% (17/33), and 14.8% (4/27), respectively, reflecting residual benefit from study drug in the parent study (figure 2). • at week 24 of the ole, pasi 90 response rates increased to 68.2% (15/22), 60.7% (17/28), 66.7% (22/33), and 74.1% (20/27) in patients initially treated with 18 mg, 90 mg, or 180 mg risankizumab or ustekinumab, respectively. figure 2. pasi 90 responses through week 24 of ole (nri) 0 20 40 60 80 100 pa tie nt s ac hi ev in g pa si 9 0 ( ) week 12 week 24 a week 0week 16 risankizumab 90 mg s.c. double-blind period open-label e tension ustekinumab 45/90 mg risankizumab 1 0 mg risankizumab 90 mg risankizumab 1 mg treatment groups from parent study 74.1 6 .2 66.7 60.7 a. the time between week 16 of the double-blind period and week 0 of the ole varied for individual patients. abbreviations: nri=non-responder imputation; ole=open-label extension; pasi=psoriasis area and severity score; s.c.=subcutaneous. • at ole entry, pasi 100 response rates for patients previously treated with 18 mg, 90 mg, or 180 mg risankizumab or ustekinumab were 0% (0/22), 39.3% (11/28), 30.3% (10/33), and 3.7% (1/27), respectively, and increased to 27.3% (6/22), 46.4% (13/28), 39.4% (12/33), and 48.1% (13/27), respectively, at week 24 of the ole (figure 3). figure 3. pasi 100 responses through week 24 of ole (nri) a. the time between week 16 of the double-blind period and week 0 of the ole varied for individual patients. abbreviations: nri=non-responder imputation; ole=open-label extension; pasi=psoriasis area and severity score; s.c.=subcutaneous. • the proportions of patients previously treated with 18 mg, 90 mg, or 180 mg risankizumab or ustekinumab achieving static physician’s global assessment scores of 0 or 1 (spga 0/1) at ole entry were 9.1% (2/22), 57.1% (16/28), 63.6% (21/33), and 25.9% (7/27), respectively, and improved to 72.7% (16/22), 67.9% (19/28), 69.7% (23/33), and 77.8% (21/27), respectively, at week 24 of the ole (figure 4). figure 4. spga scores of 0/1 through week 24 of ole (nri) a. the time between week 16 of the double-blind period and week 0 of the ole varied for individual patients. abbreviations: nri=non-responder imputation; ole=open-label extension; s.c.=subcutaneous; spga=static physician’s global assessment. • at ole entry, spga scores of 0 for patients previously treated with 18 mg, 90 mg, or 180 mg risankizumab or ustekinumab were 0% (0/22), 39.3% (11/28), 33.3% (11/33), and 7.4% (2/27), respectively, and improved to 31.8% (7/22), 46.4% (13/28), 45.5% (15/33), and 48.1% (13/27), respectively, at week 24 of the ole (figure 5). figure 5. spga scores of 0 through week 24 of ole (nri) a. the time between week 16 of the double-blind period and week 0 of the ole varied for individual patients. abbreviations: nri=non-responder imputation; ole=open-label extension; s.c.=subcutaneous; spga=static physician’s global assessment. safety • an overview of treatment-emergent aes through 24 weeks of ole for all patients who entered ole is presented in table 1. – through 24 weeks of ole, the overall rates of adverse events (aes) and serious aes were 38.2% (42 patients) and 2.7% (3 patients), respectively. – the most common ae (occurring in >5% of patients overall) was nasopharyngitis. table 2. summary of adverse events through week 24 of olea 0 20 40 60 80 100 pa tie nt s ac hi ev in g pa si 1 00 ( ) week 12 week 24week 0week 16 risankizumab 90 mg s.c. double-blind period open-label e tension ustekinumab 45/90 mg risankizumab 1 0 mg risankizumab 90 mg risankizumab 1 mg treatment groups from parent study 4 .1 27.3 46.4 39.4 a 0 20 40 60 80 100 pa tie nt s ac hi ev in g sp g a 0 /1 ( ) week 12 week 24week 0week 16 risankizumab 90 mg s.c. double-blind period open-label e tension ustekinumab 45/90 mg risankizumab 1 0 mg risankizumab 90 mg risankizumab 1 mg treatment groups from parent study 77. 72.7 67.9 69.7 a 0 20 40 60 80 100 pa tie nt s ac hi ev in g sp g a 0 ( ) week 12 week 24week 0week 16 risankizumab 90 mg s.c. double-blind period open-label e tension ustekinumab 45/90 mg risankizumab 1 0 mg risankizumab 90 mg risankizumab 1 mg treatment groups from parent study 4 .1 31. 46.4 45.5 a adverse events, n (%) risankizumab 18 mg n=22 risankizumab 90 mg n=28 risankizumab 180 mg n=33 ustekinumab 45/90 mg n=27 overall n=110 any aes 11 (50.0) 11 (39.3) 10 (30.3) 10 (37.0) 42 (38.2) drug-related aesb 0 1 (3.6) 0 1 (3.7) 2 (1.8) any ae with toxicity of grade 3 or 4 1 (4.5) 1 (3.6) 0 2 (7.4) 4 (3.6) ae leading to study drug discontinuation 0 0 0 0 0 aes of special interest 0 0 0 0 0 infections 5 (22.7) 7 (25.0) 6 (18.2) 4 (14.8) 22 (20.0) serious aesc 1 (4.5)e 1 (3.6)f 1 (3.0)g 0 3 (2.7) death 0 0 0 0 0 life-threatening 0 0 0 0 0 persistent or significant disability or incapacity 0 0 0 0 0 requires or prolongs hospitalization 1 (4.5) 1 (3.6) 1 (3.0) 0 3 (2.7) congenital anomaly or birth defect 0 0 0 0 0 other medically important serious event 1 (4.5) 0 0 0 1 (0.9) most common aesd nasopharyngitis 0 3 (10.7) 1 (3.0) 2 (7.4) 6 (5.5) upper respiratory tract infection 0 0 2 (6.1) 0 2 (1.8) a. aes through week 24 in all patients who entered ole based on their initial treatment groups. b. investigator assessed ae as possibly or probably related to study drug. c. a serious adverse event was defined as any adverse event that results in death, is immediately life-threatening, results in persistent or significant disability or incapacity, requires or prolongs hospitalization, is a congenital anomaly or birth defect, or is characterized on the basis of appropriate medical judgment as an important medical event that may jeopardize the patient and may require medical or surgical intervention. d. most common aes occurring in >5% of patients. e. one patient with basal cell carcinoma, carpal tunnel syndrome, and ulnar neuropathy. f. one patient with arthritis. g. one patient with thyroid goiter. abbreviations: ole=open-label extension; aes=adverse events. references disclosures ka papp has received honoraria or fees for serving on advisory boards, as a speaker, as a consultant, grants as an investigator from abbvie, amgen, astellas, baxalta, baxter, boehringer ingelheim, bristol-myers squibb, celgene, dermira, eli lilly, forward pharma, galderma, genentech, glaxosmithkline, janssen, kyowa-hakko kirin, leo pharma, medimmune, merck-serono, merck sharp & dohme, novartis, pfizer, regeneron, roche, sanofi-genzyme, stiefel, sun pharma, takeda, ucb, and valeant. a blauvelt has received honoraria or fees for serving on advisory boards, as a speaker, as a consultant, grants as an investigator from abbvie, aclaris, allergan, almirall, amgen, boehringer ingelheim, celgene, dermavant, dermira, eli lilly, genentech/roche, glaxosmithkline, janssen, leo, merck sharp & dohme, novartis, pfizer, purdue pharma, regeneron, sandoz, sanofi genzyme, sienna pharmaceuticals, ucb, valeant, and vidac. m flack is a full-time employee of boehringer ingelheim. y gu and ehz thompson are full-time employees of abbvie and may own stock/options. boehringer ingelheim funded the studies (nct02054481 and nct02203851), contributed to its design, and participated in data collection. abbvie participated in data analysis and interpretation of the data, and in writing, review, and approval of the publication. medical writing support was provided by deepa venkitaramani, phd, of abbvie. presented at the fall clinical dermatology conference 36th anniversary • las vega, nevada • october 12 – 15, 2017 introduction objective materials & methods results conclusions fc17posterabbviepappclinicalresponses.pdf topical treatment utilization for patients with atopic dermatitis in the united states and budget impact analysis of crisaborole ointment, 2% ryan clark,1 duygu bozkaya,1 mark levenberg,2 steven faulkner,3 timothy w. smith,3 robert a. gerber4 1 xcenda, palm harbor, fl, usa; 2pfizer inc., collegeville, pa, usa; 3pfizer inc., new york, ny, usa; 4pfizer inc., groton, ct, usa background • atopic dermatitis (ad) is a chronic inflammatory skin disease affecting between 6-13% of the population in the united states (us).1,2 • ad is often treated with prescription topical corticosteroids (tcs) and topical calcineurin inhibitors (tci). – concerns regarding local cutaneous atrophy, striae formation, and systemic side effects limit broader user of tcs.3,4 – tci are associated with application-site reactions and carry boxed warning for risk of malignancy (eg, skin and lymphoma).3-6 • crisaborole ointment is a nonsteroidal pde4 inhibitor for the treatment of mild to moderate ad. – clinical studies have demonstrated that crisaborole is effective7 and has a relatively low incidence of treatment-related/treatment-emergent adverse events in patients with mild to moderate ad.7,8 application site pain (mainly reported as burning or stinging) was the only treatment-related adverse event that occurred in >1% of patients (crisaborole: 4.4%; vehicle: 1.2%).7 objectives • the objectives of this study were: 1. to evaluate recent real-world treatment utilization and costs for tcs and tci in the us. 2. to estimate the pharmacy budget impact of crisaborole ointment, 2% over a 2-year period in patients ≥2 years of age with ad, from a third-party us payer perspective. methods real-world treatment utilization and costs (rwtuc) • the analysis assessed annual treatment patterns and associated costs of prescription topical therapies in patients who had a diagnosis of ad in 2015, using the commercial and medicare supplemental claims from the truven health analytics marketscan® research databases from 1/1/2015 through 12/31/2015. • all prescription utilization of tcs and tci was assessed, and patients were classified by strategy based on how many different treatment categories they filled during 2015. – to capture the use of combination therapy by ad patients comprised of tci and distinct categories of tcs potency, 9 mutually exclusive treatment strategies were defined: 1. tcs i-ii only (representing high potency tcs) 2. tcs iii-iv only (representing medium potency tcs) 3. tcs v-vii only (representing low potency tcs) 4. tcs i-vii (any multiple excluding above) 5. tci only 6. tci + tcs i-ii only 7. tci + tcs iii-iv only 8. tci + tcs v-vii only 9. tci + tcs i-vii (any multiple excluding above) each strategy with a tcs included at least one of the tcs strengths referred to in the group, but did not represent the order of the treatments received. the patient may have used more than one type generic drug within the same strength category. • patients with continuous enrollment for the entire calendar year 2015 were included if they had 1 or more diagnosis for ad (icd-9 = 691.8 or icd-10 = l20.*) at any time during 2015. patients <2 years of age at time of diagnosis, having invalid medication quantity (metqty <1 or >10 x tube size), or having invalid days’ supply (dayssup <1) were excluded. • marketscan data for tcs/tci pricing represents the amount eligible for payment under the plan terms after applying rules such as discounts, but before applying copayments and deductible. in the absence of pharmacy claims for crisaborole, wholesale acquisition cost (wac) is used in the bim. crisaborole budget impact model (bim) • model structure – the incremental pharmacy budget impact due to changes in market share is calculated as the difference in costs between an environment reflecting the current shares of topical ad treatments without crisaborole, and an environment with projected shares including crisaborole. • the number of patients on each treatment in each scenario (ie, “current environment” and “new environment”) and year is determined based on the size of the target population and market shares. the model then calculates the total costs based on annual per treatment per patient costs and number of patients on each treatment (figure 1). • model inputs – diagnosis and treatment rates, current market share, number of prescriptions per year, and payment (cost) per prescription were based on the real-world utilization analysis (see results section). – the percentages of patients who are 2 years and older (97.53%) were based on us census data.9 – crisaborole uptake rates of 4.7% from tcs and 20.2% from tci, with an annual increase of 1% in year 2, were assumed, based on a published bim for a tci.10 – in the absence of current crisaborole utilization data, average number of prescriptions per patient from tcs i-ii only, tcs iii-iv only, tcs v-vii only, and tci only groups was taken from the rwtuc analysis (1.46 prescriptions per year per patient). cost per crisaborole prescription is $580.00 based on wac (one 60 gram tube of crisaborole per prescription).11 figure 1. budget impact diagram current environment (without crisaborole) plan size patients diagnosed with ad patients 2 years patients receiving topical ad treatment pharmacy costs plan size patients diagnosed with ad patients 2 years patients receiving topical ad treatment pharmacy costs new environment (with crisaborole) budget impact (difference) change in market share change in pharmacy costs key: ad – atopic dermatitis. • model outputs – the results are presented over 2 years in terms of total pharmacy budget and pharmacy cost per-member per-month (pmpm) without discounting. – two ad populations were evaluated separately: patients receiving tci or tcs alone or in combination (“tcs/tci population”) and patients receiving tci alone or in combination with tcs (“tci population”; excludes tcs alone). results real-world treatment utilization and costs • more than 70% of the population was 18-64 years old; patients in the 2-11 age group have the highest ad diagnosis rate (2.4%) (table 1). • among all diagnosed patients, 50%-65% received tcs and/or tci treatment, while only 2%-7% received tci treatment with or without tcs (table 1). – based on these results, for a health plan with 1 million members, the target population size for the bim was estimated as 4,706 when the tcs/tci population was considered and 414 when the tci population was considered. • in the tci/tcs population, the majority of the patients received medium potency tcs only (40.54%); while tci population mostly used tci alone (25%) or tci combined with medium potency tcs (22.09%) (table 2). • the annual number of prescriptions per patient ranged from 1.36 to 6.41, with an annual cost per patient range of $53.11-$1,465.03 (table 2, figure 2). – patients receiving tcs had similar annual number of prescriptions (1.36-1.49 for patients receiving tcs without tci; 2.99-3.74 for patients receiving tcs with tci), with a decreasing trend towards low potency tcs. – tcis were associated with higher per-prescription costs (~$470), and medium-potency tcs were less costly (~$50), while low and high-potency tcs had similar costs (~$180). – patients using multiple types of tcs potencies in a year had the highest number of prescriptions and overall costs. crisaborole bim • for the tci/tcs population, 285 and 332 patients were estimated to receive crisaborole in years 1 and 2, respectively (figure 3). – the total budget impact of crisaborole over 2 years in the tcs/tci population was $350,946 (pmpm = $0.015), with a total budget increase of $162,106 in year 1 (pmpm = $0.014) and $188,841 in year 2 (pmpm = $0.016). • for the tci population, 84 and 88 patients were estimated to receive crisaborole in years 1 and 2, respectively (figure 3). – the total budget impact of crisaborole in the tci population was a savings of $22,871, with a total budget decrease of $11,160 in year 1 and $11,712 in year 2 (each pmpm = −$0.001) (figure 3). • for both populations, budget impact was most sensitive to changes in crisaborole cost and annual usage in one-way sensitivity analyses. presented at the 2017 fall clinical dermatology conference; october 12-15, 2017; las vegas, nv results (continued) table 1. patient demographics, and diagnosis and treatment rates from rwtuc analysis* age category (years) 2-11 12-17 18-64 65+ total age distribution among patients ≥2 years 11.39% 8.47% 71.27% 8.87% 100% number of patients by age** 111,087 82,608 695,096 86,509 975,300 ad diagnosis rate by age 2.40% 1.14% 0.54% 0.69% number of patients diagnosed with ad by age** 2,666 942 3,754 597 7,958 tci/tcs % receiving tci/tcs among diagnosed 50.30% 60.25% 65.14% 58.99% number of ad patients receiving tci/tcs treatment** 1,341 567 2,445 352 4,706 tci only % receiving tci among diagnosed 4.60% 7.13% 5.61% 2.28% number of ad patients receiving tci treatment** 123 67 211 14 414 key: ad – atopic dermatitis; bim – budget impact model; rwtuc – real-world utilization and costs; tci – topical calcineurin inhibitor; tcs – topical corticosteroid. * results are used as inputs for the bim. ** estimated for a health plan with 1 million members, where 97.53% of the population is 2 years of age and older. table 2. current market share, number of prescriptions per year, and payment per prescription from rwtuc analysis* current market share for tci/ tcs population current market share for tci population rx per patient (annual) pay per rx tci tcs i-ii tcs iii-iv tcs v-vii tci tcs i-ii tcs iii-iv tcs v-vii 1. tcs i-ii only 22.84% n/a n/a 1.69 n/a n/a n/a $153.83 n/a n/a 2. tcs iii-iv only 40.54% n/a n/a n/a 1.42 n/a n/a n/a $37.45 n/a 3. tcs v-vii only 9.63% n/a n/a n/a n/a 1.36 n/a n/a n/a $177.91 4. tcs i-vii** 18.19% n/a n/a 1.52 1.52 0.80 n/a $162.64 $50.66 $175.50 5. tci only 2.20% 25.00% 1.36 n/a n/a n/a $463.44 n/a n/a n/a 6. tci + tcs i-ii 1.42% 16.11% 1.52 2.22 n/a n/a $478.04 $194.23 n/a n/a 7. tci + tcs iii-iv 1.94% 22.09% 1.48 n/a 1.82 n/a $466.32 n/a $62.22 n/a 8. tci + tcs v-vii 0.65% 7.37% 1.44 n/a n/a 1.55 $462.31 n/a n/a $191.90 9. tci + tcs i-vii** 2.59% 29.43% 1.68 1.82 1.84 1.08 $485.45 $183.16 $64.64 $184.88 total 100% 100% key: ad – atopic dermatitis; bim – budget impact model; n/a not applicable; rwtuc – real-world utilization and costs; tci – topical calcineurin inhibitor; tcs – topical corticosteroid. * results are used as inputs for the bim. ** any multiple, excluding the strategies above. figure 2. annual per-patient prescriptions and costs 1.69 1.42 1.36 3.84 1.36 3.74 3.30 2.99 6.41 $259.61 $53.11 $242.75 $463.78 $632.54 $1,157.44 $803.22 $961.98 $1,465.03 $0 $200 $400 $600 $800 $1,000 $1,200 $1,400 $1,600 0 1 2 3 4 5 6 7 1. tcs i-ii only 2. tcs iii-iv only 3. tcs v-vii only 4. tcs i-vii 5. tci only 6. tci + tcs i-ii 7. tci + tcs iii-iv 8. tci + tcs v-vii tci + tcs i-vii a n n u a l r x c o s t p e r p a ti e n t a n n u a l n u m b e r o f r x s p e r p a ti e n t annual rx/patient annual cost/patient key: rx – prescription; tci – topical calcineurin inhibitor; tcs – topical corticosteroid. figure 3. bim results 285 332 4,292 4,031 3,989 414 389 385 0 1,000 2,000 3,000 4,000 5,000 current year 1 year 2 number of patients per treatment per year crisaborole tcs tci ± tcs a tci population 84 88 414 330 326 0 100 200 300 400 500 current year 1 year 2 number of patients per treatment per year crisaborole tci ± tcs d $0.109 $0.109 $0.123 $0.125 $0.014 $0.016 $0.000 $0.050 $0.100 $0.150 year 1 year 2 pmpm budget impact over 2 years: $0.015 without crisaborole with crisaborole b $1,311,174 $1,311,174 $1,473,279 $1,500,014 $162,106 $188,841 $0 $500,000 $1,000,000 $1,500,000 $2,000,000 year 1 year 2 total budget impact over 2 years: $350,946 without crisaborole with crisaborole c $405,793 $405,793 $394,633 $394,081 -$11,160 -$11,712 $0 $100,000 $200,000 $300,000 $400,000 $500,000 year 1 year 2 total budget impact over 2 years: -$22,871 without crisaborole with crisaborole f tcs/tci population $0.034 $0.034 $0.033 $0.033 -$0.001 -$0.001 $0.000 $0.010 $0.020 $0.030 $0.040 year 1 year 2 pmpm budget impact over 2 years: -$0.001 without crisaborole with crisaborole e key: ad – atopic dermatitis; bim – budget impact model; tci – topical calcineurin inhibitor; tcs – topical corticosteroid. references 1. hanifin jm et al. dermatitis. 2007 jun;18(2):82-91. 2. silverberg ji. jama dermatol. 2014 dec;150(12):1380. 3. eichenfield lf et al. j am acad dermatol. 2014;71:116-132. 4. schneider l et al. j allergy clin immunol. 2013;131:295-299. 5. siegfried ec et al. am j clin dermatol. 2013;14:163-178. 6. walling hw et al. clin cosmet investig dermatol. 2010;3:99-117. 7. paller as et al. j am acad dermatol. 2016 sep;75(3):494-503.e6. 8. eichenfield lf et al. j am acad dermatol. 2017 aug 17. 9. u.s. census bureau, population division. http://factfinder.census.gov. accessed april 20, 2017. 10. chang j et al. j manag care pharm. 2005 jan-feb;11(1):66-73. 11. red book online®, micromedex 2.0, truven health analytics, inc. accessed april 20, 2017. key limitations • costs associated with medical resources besides topical ad medications were excluded since data supporting differential non-medication resource use with crisaborole does not currently exist. additionally, preliminary analysis of claims data indicated that the medical visit frequencies (except those for outpatient visits) are similar in patients with and without ad. • as crisaborole is assumed to replace existing topical ad prescription treatments and is not expected to grow the number of patients treated for ad, patients untreated with prescription therapy by default do not receive crisaborole • the model does not exclude any patients based on disease severity given that the data source to populate the model (marketscan claims data) does not differentiate patients by disease severity. • if there is crisaborole uptake, it replaces all topical ad prescriptions in a year. note: this analysis does not imply comparable efficacy, safety, or product interchangeability. no head-to-head clinical studies have been conducted to assess the efficacy or safety of crisaborole vs any tcs, tci or any other prescription medications. conclusions • current utilization of topical prescription medications for ad have a material impact on pharmacy budget regardless of treatment choice. – annual per-patient costs vary widely depending on the mechanism of action (tci vs tcs) and tcs strength. • adoption of crisaborole results in a modest pharmacy budget impact or savings from the perspective of a us payer. fc17posterpfizerclarktopicaltreatmentcrisaboroleointment.pdf summary presented at the 42nd annual fall clinical dermatology conference | las vegas, nv | october 20–23, 2022 objective to report long-term infection rates in patients with moderate to severe plaque psoriasis receiving bimekizumab (bkz) 320 mg every four weeks (q4w) or every eight weeks (q8w), pooled to include 2 years of treatment across five phase 3/3b trials, the largest two-year data pool for bkz in plaque psoriasis. introduction • bkz is a monoclonal igg1 antibody that selectively inhibits interleukin (il)17f in addition to il-17a.1 • psoriasis is a chronic disease requiring long-term management; therefore, it is important to assess the long-term safety of treatments, including infection rates. materials and methods • rates of infection for treatment-emergent adverse events (teaes) over a two-year period were evaluated for all patients who received ≥1 bkz dose in be sure, be vivid, be ready, their open-label extension (ole) be bright (data cut-off: november 9, 2020), or be radiant (data cut-off: april 20, 2021).2–6 • rates of infection teaes were also evaluated separately for patients who were receiving bkz dosed 320 mg q4w or q8w at the time of the teae. • teaes were coded using meddra, medical dictionary for regulatory activities v19.0. • data are reported as exposure-adjusted incidence rates (eairs), defined as incidence of new cases reported per 100 patient-years (py), and are presented with 95% confidence intervals (cis). results • overall infection rates decreased over year 2 relative to year 1 and were lower in q8wversus q4w-treated patients (table 1). • the most common infections seen with bkz were nasopharyngitis, oral candidiasis, and upper respiratory tract infections (table 2). • no cases of active tuberculosis were reported over the two-year period. serious infections • rates of serious infections were low across bkz-treated patients (table 3). • the most common serious infections were appendicitis and cellulitis; four events of each occurred. fungal infections • the majority of fungal infections were candida infections, most of which were oral candidiasis (table 4). • rates of oral candidiasis were lower in q8wversus q4w-treated patients (figure 1; table 4); cumulative two-year rates were lower than rates for year 1 (table 4). • over two years, approximately 80% of patients experienced no oral candidiasis events. in patients who did experience such events, most had either one or two (figure 2). • the vast majority of oral candidiasis events over two years (98.1%) were mild or moderate. • five bkz q4w-treated patients discontinued bkz due to oral candidiasis in year 1 versus none in year 2; no q8w-treated patients discontinued due to oral candidiasis. opportunistic infections • rates of opportunistic infections were low (table 1); almost all were localized mucocutaneous fungal infections pre-defined as opportunistic by company convention. • exceptions to the above included one serious case each of ophthalmic herpes zoster (resolved with treatment; did not lead to discontinuation) and systemic candidiasis (resolved; patient discontinued following the event and associated pyelonephritis and obstructive nephropathy). conclusions over two years of bkz treatment, eairs of infection teaes and pre-defined infections of interest, including oral candidiasis, were generally lower in patients treated with bkz q8w compared with q4w. infection rates decreased with longer duration of bkz exposure. rates of discontinuation due to infections were low. there were no new safety findings with long-term exposure to bkz. a. armstrong,1 r.g. langley,2 k.b. gordon,3 r.b. warren,4 d. thaçi,5 l. stein gold,6 l. peterson,7 c. madden,7 n. nunez gomez,8 d. de cuyper,9 a. costanzo10 bimekizumab infection rates in patients with moderate to severe plaque psoriasis: analysis of pooled data from 2 years of treatment in phase 3 and 3b clinical trials previously presented at spin 2022 institutions: 1keck school of medicine of usc, dermatology, los angeles, california, usa; 2dalhousie university, halifax, nova scotia, canada; 3medical college of wisconsin, milwaukee, wisconsin, usa; 4dermatology centre, salford royal nhs foundation trust, manchester nihr biomedical research centre, the university of manchester, manchester, uk; 5comprehensive centre for inflammation medicine, university of lübeck, lübeck, germany; 6henry ford health system, detroit, michigan, usa; 7ucb pharma, raleigh, north carolina, usa; 8ucb pharma, monheim, germany, 9ucb pharma, brussels, belgium; 10dermatology, humanitas clinical and research centre, irccs, rozzano, milan, italy. references: 1papp ka et al. j am acad dermatol 2018;79:277–85; 2warren rb et al. n engl j med 2021;385:130–41, nct03412747 be sure; 3reich k et al. lancet 2021;397:487–98, nct03370133 be vivid; 4gordon kb et al. lancet 2021;397:475–86, nct03410992 be ready; 5clinicaltrials.gov, nct03598790 be bright; 6reich k et al. n engl j med 2021;385:142–52, nct03536884 be radiant. author contributions: substantial contributions to study conception/design, or acquisition/analysis/interpretation of data: aa, rgl, kbg, rbw, dt, lsg, lp, cm, nng, ddc, ac; drafting of the publication, or revising it critically for important intellectual content: aa, rgl, kbg, rbw, dt, lsg, lp, cm, nng, ddc, ac; final approval of the publication: aa, rgl, kbg, rbw, dt, lsg, lp, cm, nng, ddc, ac. author disclosures: aa: served as a research investigator and/or scientific advisor to abbvie, almirall, arcutis, aslan, boeringer ingleheim, bms, dermavant, dermira, eli lilly, epi, incyte, janssen, leo pharma, nimbus, novartis, ortho dermatologics, pfizer, regeneron, sanofi, sun pharma, and ucb pharma. rgl: principal investigator for abbvie, amgen, boehringer ingelheim, celgene, eli lilly, leo pharma, merck, novartis, pfizer, and ucb pharma; served on scientific advisory boards for abbvie, amgen, boehringer ingelheim, celgene, eli lilly, leo pharma, merck, novartis, pfizer, and ucb pharma; provided lectures for abbvie, amgen, celgene, eli lilly, leo pharma, merck, novartis, and pfizer. kbg: received consulting fees from abbvie, almirall, amgen, boehringer ingelheim, bms, celgene, dermira, eli lilly, janssen, novartis, pfizer, sun pharma, and ucb pharma; research support from abbvie, bms, celgene, eli lilly, janssen, novartis, and ucb pharma. rbw: supported by the nihr manchester biomedical centre; consulting fees from abbvie, almirall, amgen, arena, astellas, avillion, biogen, bms, boehringer ingelheim, celgene, eli lilly, gsk, janssen, leo pharma, novartis, pfizer, sanofi, and ucb pharma; research grants to his institution from abbvie, almirall, janssen, leo pharma, novartis, and ucb pharma; honoraria from astellas, dice, gsk, and union. dt: honoraria for participation on advisory boards, as a speaker, and for consultancy from abbvie, almirall, amgen, biogen, boehringer ingelheim, bms, celgene, eli lilly, galapagos, janssen, leo pharma, morphosis, novartis, pfizer, regeneron, samsung, sandoz, sanofi genzyme, and ucb pharma; research grants received from celgene, leo pharma, and novartis. lsg: consultant for abbvie, amgen, arcutis, dermavant, leo pharma, novartis, pfizer, sanofi-regeneron, and ucb pharma; principal investigator for abbvie, arcutis, dermavant, leo pharma, novartis, and ucb pharma. lp, cm, nng, ddc: employees and shareholders of ucb pharma. ac: investigator and/or speaker and/or advisor for abbvie, almirall, amgen, boehringer ingelheim, celgene, eli lilly, galderma, janssen, leo pharma, novartis, pfizer, regeneron, sandoz, sanofi, and ucb pharma. acknowledgments: these studies were funded by ucb pharma. we thank the patients and their caregivers in addition to the investigators and their teams who contributed to this study. the authors acknowledge susanne wiegratz, msc, ucb pharma, monheim, germany, for publication coordination, emma francis-gregory, ba, costello medical, cambridge, uk, for medical writing and editorial assistance and the costello medical design team, for graphic design assistance. figure 2 patients with oral candidiasis teaes bkz: bimekizumab; ci: confidence interval; eair: exposure-adjusted incidence rate; il: interleukin; meddra: medical dictionary for regulatory activities; nec: not elsewhere classified; ole: open-label extension; py: patient-years; q4w: every four weeks; q8w: every eight weeks; teae: treatment-emergent adverse event. figure 1 eairs of oral candidiasis over two years by treatment period and continuous bkz dosing a) year 1a for patients who received both bkz 320 mg q4w and q8w doses during the trials, teaes were assigned to the dose most recently received prior to the date of onset of the teae. patients who received both bkz 320 mg q4w and q8w at different times in the trials were included in the population count of both treatment groups, but only once in each bkz total group. data were pooled for all patients who received ≥1 bkz dose in be sure, be vivid, be ready, their ole be bright (data cut-off: november 9, 2020), or be radiant (data cut-off: april 20, 2021).2–6 abe vivid did not use q8w dosing; bbe radiant is comprised of a 48-week double-blinded study period and an ongoing ole. data from both study periods were included here; the trial is included in the total numbers of both double-blinded trials and oles. the most common infections were nasopharyngitis, oral candidiasis, and upper respiratory tract infection 98.1% of oral candidiasis events observed over two years were mild or moderate rates of serious infections were low in all groups and did not increase with longer duration of bkz exposure b) cumulative over 2 yearsa 1,767/2,186 (80.8%) patients did not experience any oral candidiasis events over two years. adata are reported from weeks 0–104 of treatment. 1,836/2,186 (84.0%) patients did not experience any oral candidiasis events over year 1. ayear 1 includes data from weeks 0–52 of treatment. error bars/values in parentheses represent 95% cis. data are reported for all patients who received bkz at week 16 and received either bkz q4w or q8w continuously during the maintenance period and in the ole. all patients received bkz q4w through weeks 0–16. afor weeks 52–104, n=233 for bkz q4w only and n=416 for bkz q4w/q8w only. ayear 1 includes data from weeks 0–52 of treatment; byear 2 includes data from weeks 52–104 of treatment. ayear 1 includes data from weeks 0–52 of treatment; byear 2 includes data from weeks 52–104 of treatment. ayear 1 includes data from weeks 0–52 of treatment; byear 2 includes data from weeks 52–104 of treatment. ayear 1 includes data from weeks 0–52 of treatment; byear 2 includes data from weeks 52–104 of treatment; cthere was one serious, severe case of esophageal candidiasis in a patient receiving bkz 320 mg q4w during the first year of treatment which led to discontinuation. table 1 overall infection rates table 2 most common infections table 3 serious infections table 4 fungal infections n=2,025 2,329 py 4 doubleblinded trials and 2 olesb dosing population exposure trials administered n=2,186 n=1,576 3,796 py 1,471 py bkz total bkz q4w bkz q8wa 3 doubleblinded trials and 2 olesb 4 doubleblinded trials and 2 olesb 50 5 10 15 20 25 30 35 40 45 0 30.5 (19.9, 44.7) 29.7 (21.1, 40.6) 18.2 (12.5, 25.7) 22.9 (17.6, 29.3) 16.1 (11.0, 22.9) 7.2 (4.7, 10.6) bkz q4w (n=289)a bkz q4w/q8w (n=446)a treatment period weeks 16–52 weeks 52–104weeks 0–16 e a ir /1 0 0 p y 1 percentage of patients (%)n u m b e r o f o ra l c a n d id ia si s t e a e s e x p e ri e n c e d b y t h e sa m e p a ti e n t 0 10 20 30 40 50 60 70 80 90 100 2 3 4 ≥5 0.3% 0.6% 1.4% 4.1% 9.6% bkz total (n=2,186) n u m b e r o f o ra l c a n d id ia si s t e a e s e x p e ri e n c e d b y t h e sa m e p a ti e n t bkz total (n=2,186)1 percentage of patients (%) 0 10 20 30 40 50 60 70 80 90 100 2 3 4 ≥5 1.0% 1.2% 2.1% 4.7% 10.2% 98.1% year 1a year 2b cumulative over two years bkz total n=2,186 bkz total n=1,710 bkz 320 mg q4w n=2,025 bkz 320 mg q8w n=1,576 bkz total n=2,186 summary of treatment exposure total exposure, py 2,049 1,291 2,329 1,471 3,796 summary of infection teaes, eair/100 py (95% ci) any infection teae 116.8 (110.6, 123.1) 83.7 (77.8, 90.0) 110.2 (104.2, 116.5) 77.7 (71.9, 83.9) 93.9 (89.3, 98.7) opportunistic infections 1.8 (1.3, 2.5) 0.5 (0.2, 1.1) 1.7 (1.2, 2.3) 0.5 (0.2, 1.0) 1.2 (0.9, 1.6) staphylococcal infections 1.5 (1.0, 2.1) 0.9 (0.5, 1.6) 1.3 (0.9, 1.9) 0.9 (0.5, 1.5) 1.1 (0.8, 1.5) streptococcal infections 1.1 (0.7, 1.7) 1.0 (0.5, 1.7) 1.0 (0.6, 1.4) 1.1 (0.6, 1.8) 1.0 (0.7, 1.4) leading to discontinuation 1.1 (0.7, 1.6) 0.3 (0.1, 0.8) 0.9 (0.6, 1.4) 0.3 (0.1, 0.8) 0.7 (0.5, 1.0) active tuberculosis 0.0 0.0 0.0 0.0 0.0 year 1a year 2b cumulative over two years bkz total n=2,186 bkz total n=1,710 bkz 320 mg q4w n=2,025 bkz 320 mg q8w n=1,576 bkz total n=2,186 most common infection teaes, eair/100 py (95% ci) nasopharyngitis 25.2 (22.9, 27.7) 17.8 (15.4, 20.3) 22.0 (19.9, 24.2) 15.5 (13.5, 17.9) 18.4 (17.0, 20.0) oral candidiasis 18.4 (16.5, 20.5) 13.3 (11.3, 15.5) 17.1 (15.4, 19.0) 10.5 (8.9, 12.4) 13.0 (11.8, 14.3) upper respiratory tract infection 10.3 (8.9, 11.8) 7.3 (5.9, 9.0) 8.8 (7.6, 10.2) 7.3 (5.9, 8.8) 7.8 (6.9, 8.8) year 1a year 2b cumulative over two years bkz total n=2,186 bkz total n=1,710 bkz 320 mg q4w n=2,025 bkz 320 mg q8w n=1,576 bkz total n=2,186 summary of serious infection teaes, eair/100 py (95% ci) serious infections 1.7 (1.2, 2.3) 0.5 (0.2, 1.1) 1.4 (1.0, 2.0) 0.9 (0.5, 1.5) 1.2 (0.9, 1.6) most common serious infection teaes (four events each over two years), eair/100 py (95% ci) appendicitis 0.1 (0.0, 0.4) 0.1 (0.0, 0.4) 0.0 (0.0, 0.2) 0.2 (0.0, 0.6) 0.1 (0.0, 0.3) cellulitis 0.1 (0.0, 0.4) 0.0 0.2 (0.0, 0.4) 0.0 0.1 (0.0, 0.3) year 1a year 2b cumulative over two years bkz total n=2,186 bkz total n=1,710 bkz 320 mg q4w n=2,025 bkz 320 mg q8w n=1,576 bkz total n=2,186 summary of fungal infection teaes, eair/100 py (95% ci) fungal infections 29.8 (27.3, 32.5) 22.7 (20.0, 25.6) 27.4 (25.1, 29.9) 19.0 (16.7, 21.6) 21.9 (20.2, 23.6) candida infections 21.5 (19.4, 23.7) 15.5 (13.4, 17.9) 19.9 (18.0, 21.9) 11.9 (10.1, 13.9) 15.0 (13.6, 16.4) oral candidiasis 18.4 (16.5, 20.5) 13.3 (11.3, 15.5) 17.1 (15.4, 19.0) 10.5 (8.9, 12.4) 13.0 (11.8, 14.3) oropharyngeal candidiasis 1.2 (0.8, 1.8) 0.2 (0.0, 0.7) 1.0 (0.7, 1.5) 0.2 (0.0, 0.6) 0.7 (0.5, 1.0) vulvovaginal candidiasis 1.1 (0.7, 1.6) 0.5 (0.2, 1.0) 1.0 (0.6, 1.4) 0.3 (0.1, 0.8) 0.7 (0.5, 1.0) skin candidiasis 0.8 (0.5, 1.3) 1.1 (0.6, 1.8) 0.9 (0.5, 1.3) 0.8 (0.4, 1.4) 0.9 (0.6, 1.2) esophageal candidiasis 0.2 (0.1, 0.6)c 0.0 0.2 (0.0, 0.4)c 0.1 (0.0, 0.4) 0.1 (0.0, 0.3)c tinea infections 3.8 (3.0, 4.7) 2.4 (1.6, 3.4) 3.2 (2.5, 4.1) 2.9 (2.1, 4.0) 2.9 (2.4, 3.5) fungal infections nec 4.5 (3.6, 5.5) 4.7 (3.6, 6.0) 4.2 (3.4, 5.2) 3.4 (2.5, 4.5) 3.7 (3.1, 4.3) skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 171 brief articles weight gain over time in hidradenitis suppurativa patients: trends and implications shanice a mckenzie bs,1 nirali patel ms,1 christina l harview md,2 allison k truong md,3 lucia y chen ms,4 tristan r grogan ms,4 vivian y shi md,5 richard g bennett md,1,6 jennifer l hsiao md1 1division of dermatology, department of medicine, david geffen school of medicine, university of california, los angeles, los angeles, ca 2department of dermatology, university of iowa, iowa city, ia 3department of dermatology, cedars-sinai medical center, los angeles, ca 4department of medicine statistics core, david geffen school of medicine, university of california, los angeles, los angeles, ca 5division of dermatology, department of medicine, the university of arizona, tucson, az 6division of dermatology, department of medicine, keck school of medicine, university of southern california, los angeles, ca hidradenitis suppurativa (hs) is a chronic inflammatory skin disorder with a significant comorbidity burden. obesity is a modifiable risk factor that is strongly associated with hs. recent evidence suggests that hs patients are 17.3 times more likely to be obese than healthy controls.1,2 furthermore, introduction background: hidradenitis suppurativa (hs) is often seen in overweight and obese patients. however, little is documented about weight gain over time in hs patients. methods: from august 2009 to march 2018, all patients in the ucla hs clinic were asked at initial examination about their weight gain since high school. results: a cohort of 143 hs patients were found to have a significant mean bmi increase of 4.7 (25.5 to 30.2, p<0.0001) from high school until time of presentation (approximately a 15 year interval). of the patients with ≥10 point bmi increase, 85.2% were women. 59.6% of women were normal weight in high school with an average bmi of 24.8 (sd 6.41, range 14-50) and 78.7% were overweight or obese at time of hs clinic intake. hispanic hs patients were found to have more weight gain than other ethnic groups, (p=0.09) which may be clinically significant. conclusions: although many hs patients were normal weight or mildly overweight in high school, most become obese in early adulthood. since obesity is thought to increase hs severity, weight management should be stressed in hs patients early on before weight gain occurs. abstract skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 172 hs patients are 2.22 times more likely than controls to develop metabolic syndrome (mets), which includes obesity, hypertension, hyperlipidemia, and diabetes.3 thus, hs patients are at high risk for adverse cardiovascular (cv) outcomes. compared to matched controls, hs patients have an increased risk for mi (or 1.57; 95%ci 1.142.17), ischemic stroke (or 1.33; 95%ci 1.011.76), and cv-associated death (1.95; 95%ci 1.42-2.67).4 there is little literature on weight gain over time in hs patients, and even more sparse evidence on which sub-populations are at increased risk for weight gain. the aim of this study is to examine the body mass index (bmi) change over time in a cohort of hs patients. a retrospective chart review was conducted on 143 sequential hs patients who were seen at the ucla hs specialty clinic from 2009 to 2018. patient demographics, medical history related to hs, weight in high school and weight and height at initial presentation were abstracted. the bmi was calculated by weight in kilograms divided by height in meters squared. a paired t-test and mcnemar’s test were used to compare bmi in high school and bmi at initial presentation. paired t-tests were used for all subgroup analyses. all analyses were performed in r (v3.5.1 vienna, au) and p-values < 0.05 were considered to be statistically significant. patient characteristics are reported in table i. 43% of the patients reported having hs symptoms by age 18 and the average duration from high school to presentation at hs clinic was 14.8 years. the mean bmi in high school was 25.5 (sd6.69, range 14-54) and the mean bmi at the time of presentation to hs clinic was 30.2 (sd7.59, range 19-60). this increase in bmi was significant (p<0.0001). furthermore, a significantly higher proportion of patients reported a weight and height that would qualify them for being obese (bmi≥30) at time of presentation compared to high school (46% vs. 19%, p<0.0001). 59.6% of women were normal weight in high school with an average bmi of 24.8 (sd6.41, range 14-50); however, 78.7% were overweight or obese at the time of hs clinic intake. women tended to gain more weight than men, though not statistically significant. family history of hs and race do not appear to significantly influence weight gain, although hispanics (78.2% mexican) tended to have higher bmi gain than that in other ethnic groups. (table ii). 18.9% of the patients (n=27) had a ≥10 point bmi increase, most commonly hispanic (22.2%) and white (22.2%), followed by bi or multi racial (14.9%) and black (11.1%) patients. among them, 85.2% were women and 74.1% did not have a family history of hs (figure 1). a large number of patients in this cohort reported significant weight gain between high school and presentation to hs specialty clinic. in high school, patients were mildly overweight (mean bmi 25.5) and approximately 1 in 5 were obese (bmi≥30). at the time of presentation, the mean bmi increased to 30.2 and the percentage with obesity more than doubled (2.4x) with nearly 1 in 2 patients being obese. given the methods discussion results skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 173 table i. patient variables. total patient number 143 gender, n (%) female 94 (65.7%) male 49 (34.3%) presentation age to ucla hs clinic, mean (range) 32.8 (15-65) onset age of hs, mean (range)* 22.1 (6-63.5) bmi in high school, mean (range) 25.5 (14-54) bmi at presentation, mean (range) 30.2 (19-60) race/ethnicity, n (%)** white 41 (28.7%) hispanic 23 (16.1%) black 19 (13.3%) middle eastern 12 (8.4%) non-indian asian 10 (7%) indian asian 6 (4.2%) native american 1 (0.7%) bior multi-racial 25 (17.5%) family history, n (%)*** yes 39 (27.3%) no 98 (68.5%) *unknown for 5 patients; **unknown for 4 patients; ***unknown for 6 patients table ii. bmi changes within patient subgroups. high school bmi, mean current bmi, mean p value gender males, n = 49 27.0 30.6 p=0.20 females, n = 94 24.8 30.0 p=0.20 family history of hs yes, n = 39 26.9 30.8 p=0.45 no, n = 98 25.2 30.1 p=0.45 race/ethnicity white, n = 41 25.2 29.0 black, n = 19 26.8 32.2 p=0.41 hispanic, n = 23 29.9 36.7 p=0.09 middle eastern, n = 12 22.6 26.5 p=0.82 native american, n = 1 17 28 - asian, n = 10 24.5 28.7 p=0.94 south asian, n = 6 25.3 28.3 p=0.65 bi or multi-racial, n = 25 24.3 28.2 p=0.93 skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 174 figure 1. characteristics of 27 patients with ≥10 kg/m2 increase in bmi key: y=yes, n=no, w=white, h=hispanic, bi/m=bi/multicultural, na=native american, a=asian, o=other negative impact of weight gain on hs disease course and its cardiovascular comorbidities, identifying at-risk patients and initiating weight reduction strategies early is important. the effects of obesity in hs are both metabolic and physical. metabolic activity in adipose tissue produces a subacute inflammatory state, secreting increased levels of il-1, il-6, tnfα, c-reactive protein.5 persistent and heightened release of these pro-inflammatory cytokines may increase keratinocyte proliferation, contributing to follicular occlusion observed in hs.5 in patients with a high bmi, increased friction in intertriginous areas causes increased moisture, retention of hair follicle material, epidermal hyperplasia, and follicular rupture further contributing to hs development.1 previous studies have shown a significant correlation between increased bmi and hs severity as measured by hurley score.6 normal weight patients with subsequent weight gain report increased hs severity.7 several case reports have demonstrated symptom improvement and even disease remission in hs patients who achieved large weight reduction following bariatric surgery.8,9 overall, obesity is the most frequently observed component of the mets.10 a 2015 study found that hs was significantly associated with each individual component of mets, including obesity (or 1.71; 95%ci 1.53-1.91), diabetes (or 1.41; 95%ci 1.191.66), hyperlipidemia (or 1.14; 95%ci 1.021.28), and hypertension (or 1.19; 95%ci 1.03-1.38) when compared to controls.11 progressive weight gain is noted in adulthood in the general u.s. population, with mean bmi trending from 27.6 in the second decade to 29.4 in the third decade for women and 27.2 in the second decade and 28.9 in the third decade for men.12 however, weight gain deserves special attention in hs patients me skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 175 since obesity has serious consequences for hs patients compared to non-hs patients with regard to disease severity and risk of cardiovascular disease. the reported progression from mildly overweight bmi in high school to obese bmi in mid adulthood in this study suggests that hs patients may benefit from early weight management. hispanic patients especially tended to have large weight gain and women comprised the majority of individuals with ≥10 point bmi increase, which may represent particularly high-risk groups of hs patients, highlighting the importance of targeting these groups. limitations of this study include its confinement to a single academic center cohort and the small sample size. in addition, inaccurate estimation of high school weight and height and weight at presentation is also possible. while obesity is highly associated with hs, our study found that most patients were normal weight or only mildly overweight in adolescence. identifying hs patients who are potentially at great risk of weight gain, such as women and hispanics, before they become obese is crucial for early intervention. acknowledgement: statistical analyses were supported by the nih national center for advancing translational science (ncats) ucla ctsi grant number ul1tr001881. conflict of interest disclosures: vivian shi is a stock shareholder of learn health, and has served as a consultant or investigator for, or has received research funding, from sanofi/regeneron, eli lilly, dermira, novartis, abbvie, sun pharma, pfizer, leo, menlo therapeutics, burt’s bees, gpskin, and skin actives scientific unrelated to the content of this manuscript. sam, np, clh, akt, lyc, trg, rgb, and jlh have no conflicts of interest to declare. funding: none corresponding author: jennifer hsiao md 2020 santa monica blvd. suite 510 santa monica, ca 90404 phone: (310) 917-3376 email: jhsiao@mednet.ucla.edu references: 1. boer j, nazary m, riis pt. the role of mechanical stress in hidradenitis suppurativa. dermatol clin. 2016;34(1):37-43. doi:10.1016/j.det.2015.08.011 2. shlyankevich j, chen aj, kim ge, kimball ab. hidradenitis suppurativa is a systemic disease with substantial comorbidity burden: a chartverified case-control analysis. j am acad dermatol. 2014;71(6):1144-1150. doi:10.1016/j.jaad.2014.09.012 3. tzellos t, zouboulis cc, gulliver w, cohen ad, wolkenstein p, jemec gbe. cardiovascular disease risk factors in patients with hidradenitis suppurativa: a systematic review and metaanalysis of observational studies. br j dermatol. 2015;173(5):1142-1155. doi:10.1111/bjd.14024 4. egeberg a, gislason gh, hansen pr. risk of major adverse cardiovascular events and allcause mortality in patients with hidradenitis suppurativacardiovascular events and all-cause mortality in hidradenitis suppurativacardiovascular events and all-cause mortality in hidradenitis suppurativa. jama dermatology. 2016;152(4):429-434. doi:10.1001/jamadermatol.2015.6264 5. nazary m, van der zee hh, prens ep, folkerts g, boer j. pathogenesis and pharmacotherapy of hidradenitis suppurativa. eur j pharmacol. 2011;672(1-3):1-8. doi:10.1016/j.ejphar.2011.08.047 6. schrader amr, deckers ie, van der zee hh, boer j, prens ep. hidradenitis suppurativa: a retrospective study of 846 dutch patients to identify factors associated with disease severity. j am acad dermatol. 2014;71(3):460-467. doi:10.1016/j.jaad.2014.04.001 7. riis pt, saunte dm, benhadou f, marmol v, guillem p, beksac b. low and high body mass index in hidradenitis suppurativa patients — different subtypes ? j eur acad dermatology conclusion mailto:jhsiao@mednet.ucla.edu skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 176 venereol. 2018;32(2):307-312. doi:10.1111/jdv.14599 8. thomas cl, gordon kd, mortimer ps. rapid resolution of hidradenitis suppurativa after bariatric surgical intervention. clin exp dermatol. 2014;39(3):315-318. doi:10.1111/ced.12269 9. gallagher c, kirthi s, burke t, o’shea d, tobin am. remission of hidradenitis suppurativa after bariatric surgery. jaad case reports. 2017;3(5):436-437. doi:10.1016/j.jdcr.2017.06.008 10. gierach m, gierach j, ewertowska m, arndt a, junik r. correlation between body mass index and waist circumference in patients with metabolic syndrome. isrn endocrinol. 2014;2014(514589). 11. shalom g, freud t, harman-boehm i, polishchuk i, cohen ad. hidradenitis suppurativa and metabolic syndrome: a comparative crosssectional study of 3207 patients. br j dermatol. 2015;173(2):464-470. doi:10.1111/bjd.13777 12. fryar cd, gu q, ogden cl, flegal km. anthropometric reference data for children and adults: united states, 2011-2014. vital health stat 3. 2016;(39):1-46. patient tolerability of tazarotene foam, 0.1%, and impact on patient compliance real world patient perceptions of the use of tazarotene 0.1% foam in the treatment of acne vulgaris james q. del rosso do, faocd, faad; 1 corey l. hartman md faad; 2 caitlin lewis phd; 3 rhonda schreiber msrn.4 1. dréno b, thiboutot d, gollnick h, finlay ay, layton a, leyden jj, leutenegger e, perez m; global alliance to improve outcomes in acne. large-scale worldwide observational study of adherence with acne therapy. int j dermatol. 2010 apr;49(4):448-56. 2. kircik lh. importance of vehicles in acne therapy. j drugs dermatol. 2011 jun;10(6):s17-23. 3. del rosso jq, kircik lh, zeichner j, stein gold l.. the clinical relevance and therapeutic benefit of established active ingredients incorporated into advanced foam vehicles: vehicle characteristics can influence and improve patient outcomes. j drugs dermatol. 2019 feb 1;18(2s):s100-s107. 4. eastman wj, malahias s, delconte j, dibenedetti d. assessing attributes of topical vehicles for the treatment of acne, atopic dermatitis, and plaque psoriasis. cutis. 2014 jul;94(1):46-53. 5. smith ja, narahari s2, hill d, feldman sr. tazarotene foam, 0.1%, for the treatment of acne. expert opin drug saf. 2016 jan;15(1):99-103. 6. feldman sr, werner cp, alió saenz ab. the efficacy and tolerability of tazarotene foam, 0.1%, in the treatment of acne vulgaris in 2 multicenter, randomized, vehicle-controlled, double-blind studies. j drugs dermatol. 2013 apr;12(4):438-46. 7. epstein el, stein gold l. safety and efficacy of tazarotene foam for the treatment of acne vulgaris.clin cosmet investig dermatol. 2013 may 14;6:123-5. 8. data on file, mayne pharma. references 1. jdr dermatology research/thomas dermatology, las vegas, nv; touro university, henderson, nv; 2. skin wellness dermatology, birmingham, al; university of alabama birmingham, al; 3. clewy communications, raleigh, nc. 4. mayne pharma, greenville, nc. these surveys and analysis were sponsored by mayne pharma. disclosure total respondents through week 12 n=372 n(%) gender male 118 (31.7) female 252 (67.7) other 2 (0.6) age 12-20 107 (29) 21-30 121 (33) 31+ 143 (38) race caucasian 252 (68) african american 36 (10) hispanic or latino 46 (12) other 37 (10) conclusion in the 12 week survey, participants were asked “overall how satisfied are you with tazarotene 0.1% foam?”. satisfaction rates increased from week 4 to week 12 and of the 371 patients who responded to this question at week 12, 71% stated they were either very satisfied or satisfied with tazarotene 0.1% foam and 69% were satisfied with the clearance of acne achieved during the survey period. while satisfaction was favorable overall the highest levels were reported by the following subsets: female patients, those who used the product on their face only, those who used the product in winter, and those who used the product most consistently. satisfaction increased slightly with age, however the difference between the 3 sub-groups of age was quite low. the same can be seen across the various races who participated in the surveys. while non-white responders reported slightly higher levels of satisfaction, the differences between the sub-groups are also low. while common perception is that foams are suited better to large treatment areas and topical retinoids are poorly tolerated on the face, the data in these surveys showed a higher satisfaction with those using tazarotene 0.1% foam on the face than those using it on the trunk only or face and trunk. when satisfaction was rated based on season of use, tazarotene 0.1% foam again showed results that contradict traditional views that topical retinoids are not well tolerated in the dry winter months. in these satisfaction was very similar regardless of season of use, with participants using the product during the winter months actually rating satisfaction slightly higher. participants who reported using the product daily or every other day on every survey were defined as ‘consistent use’ (n=215). those who marked an option other than daily or every other day use on any survey were defined as ‘some inconsistent use’ (n=156). a subset of the latter group were those who never reported daily or every other day use, defined as ‘only inconsistent use’ (n=61). patients in the ‘consistent use’ group reported slightly greater satisfaction rates, which aligns with expectations that consistent use or adherence to treatment regimen should result in increased satisfaction with treatment outcomes. acne vulgaris (av) is the most common inflammatory skin disorder seen in outpatient dermatology clinics in the united states. both adolescents and adults of all races and genders are frequently affected. in addition to the impact of av on physical appearance, there are several adverse psychosocial consequences that impair quality of life. continued patient compliance with topical therapies is a recognized barrier to optimal treatment of chronic disorders such as av.1 patient satisfaction with a topical vehicle formulation strongly influences adherence with treatment.2-4 tazarotene 0.1% foam is the only retinoid approved for use in a foam vehicle and is well established as an effective, safe, and well tolerated topical treatment for av.5-7 data from the phase iii studies evaluating tazarotene 0.1% foam for av supported positive patient experiences with both therapeutic outcomes and formulation characteristics.8 these overall positive patient experiences from clinical trial patients in a controlled setting prompted a subsequent analysis using a series of surveys administered to current users of tazarotene 0.1% foam to gather perspectives on its use in “real world” clinical practice. patients with av on the face and/or trunk who were being treated with tazarotene 0.1% foam were asked to rate their experiences of using the product over the course of 12 weeks. introduction • around 3000 survey kits were distributed across the usa to capture data from diverse geographical areas and climates • two waves of the survey were administered in order to capture use in the winter months as well as non-winter months • surveys were administered at baseline, weeks 2, 4, 8 and 12 • feedback was gathered on overall patient satisfaction with use of the product, perceived therapeutic impact on av, and topical vehicle preference • after registering at baseline patients completed surveys within 3 days of the 2, 4, 8, and 12 week dates to ensure feedback was gathered at the specific time points • patient responses were gathered and tabulated by a third party vendor to ensure consistency of reporting and objectivity of analysis • a total of 372 patients participated in the surveys through week 12 with a broad range of diversity across gender, age, and race (not all responded to every question; n values = number of respondents to each question in results graphs) methods discussion it is well known that topical vehicle formulation can significantly alter drug delivery and therefore impact safety, efficacy and tolerability.3 in recent years aqueous-based foam formulations have become a preferred vehicle in treating skin disease as their favorable tolerability and cosmetic elegance have led to positive patient preference, increasing the likelihood that adherence to treatment regimens including these foam vehicles will also improve. however, early foam formulations were positioned for use in diseases that affected large body surface areas, leading to a general belief amongst clinicians that the foams were only suitable for large areas, such as the trunk, due to their spreadability.3 in addition, the strength of tazarotene as a topical retinoid, the dryness and irritation commonly associated with early formulations, and lack of familiarity with proper application techniques has also led clinicians to avoid use of tazarotene 0.1% foam on the face and during the dry winter months, regardless of its novel foam formulation and the efficacy shown in phase iii trials. the results of specific questions from the surveys that address these historical perceptions of topical tazarotene and foam formulations were tabulated and can be seen in the graphs to the right. the data presented here, captured from patients who had completed 12 weeks of treatment using the novel foam formulation of tazarotene 0.1% foam, represent a significant sample size with diversity across gender, race, and age. these results contradict many prior assertions regarding topical tazarotene products. patient satisfaction levels increased over the treatment period and after 12 weeks of treatment were consistently high across gender, age and race, regardless of the time of year the treatment was used or the area of the body being treated. overall, these real-world responses support the results of patient questionnaires from the phase iii studies, with tazarotene 0.1% foam being rated by a strong majority of patients as an effective, tolerable, and easy-to-use treatment option for av of the face and body. 41 50 55 54 47 45 46 8 41 38 38 38 39 33 40 24 15 11 6 7 8 17 11 25 p e rc e n t o f r e sp o n d e n ts overall product attribute rating (n=371*) excellent good fair 82% 88% 93%92%93% 88% 86% 32% 56% 19% 14% 11% foam cream gel lotion p e rc e n t o f r e sp o n d e n ts treatment formulation rating (n=371*) *371 of the total 372 participants completed this question at week 12 participants were asked to rate a number of qualities of tazarotene 0.1% foam at all time points during the surveys. the product rated very strongly, largely as excellent or good, in all attributes with the exception of moisturizing. however, given that topical retinoids have been historically considered to be drying, a total of 32% of respondents ranking “moisturizing” as excellent or good speaks favorably to the novel tazarotene 0.1% foam vehicle. participants were asked to rank topical vehicles on a scale of 1 to 5, with 1 being the most preferred formulation and 5 being the least preferred. foam vehicle formulations received the highest ranking by far, with 56% of respondents rating it as “most preferred”. this is between 2-5 times greater than the other vehicles, with the next highest being cream at only 19% of subjects rating it “most preferred”. patients were asked to rate their satisfaction with tazarotene 0.1% foam on all surveys. patient satisfaction with the product increased over the course of 12 weeks and dissatisfaction remained very low throughout. at week 12, 71% of respondents indicated they were very satisfied or satisfied with tazarotene 0.1% foam and 67% indicating that they were likely or very likely to continue use of the product while only 6% stated they were unlikely to continue.8 *371 of the total 372 participants completed this question at week 12 *n=participants who completed this question at each time point 35 32 26 38 19 36 45 32 39 39 41 39 32 28 32 37 35 34 25 36 37 42 33 44 36 29 35 31 37 41 37 33 35 37 35 37 33 38 p e rc e n t o f r e sp o n d e n ts overall satisfaction week 12 (n=371*) very satisfied satisfied consistency of useseason of uselocation of useraceagegenderwhole cohort 71% 69% 66% 71% 63% 72% 74% 67% 70% 76% 82% 76% 65% 63% 69% 72% 72% 67% 63% *371 of the total 372 participants completed this question at week 12 % at top of bars = total respondents who were very satisfied or satisfied % at top of bars = total respondents who were very satisfied or satisfied % at top of bars = sum of excellent and good % at top of bars = total respondents who ranked each product as most preferred results 9 21 29 35 39 42 40 36 43 26 20 18 6 7 8 9 2 3 2 4 week 2 (n=282) week 4 (n=309) week 8 (n=299) week 12 (n=371) p e rc e n t o f r e sp o n d e n ts satisfaction over course of treatment very satisfied satisfied neutral dissatisfied very dissatisfied 48% 63% 69% 71% skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 272 brief articles successful treatment of granuloma annulare with certolizumab aidan martinez1, joseph han2, nahla shihab, md3, mark lebwohl, md4 1research assistant, icahn school of medicine at mount sinai, new york, ny 2medical student, icahn school of medicine at mount sinai, new york, ny 3clinical dermatology fellow, department of dermatology, icahn school of medicine at mount sinai, new york, ny 4professsor and chairman, department of dermatology, icahn school of medicine at mount sinai, new york, ny granuloma annulare (ga) is a common skin disorder, classically presenting as annular erythematous papules and plaques.1 the most common type of ga is the localized form, accounting for about 75% of all reported cases. this form is usually selflimited, treatment is primarily indicated for cosmetic reasons and associated impact on self-image and quality of life.2 a less common type is generalized ga, which can be diagnosed by the presence of generalized skin-colored plaque and papules varying in sizes.3 unlike the localized form, generalized ga is often pruritic. in addition, this subtype rarely resolves spontaneously and is fairly unresponsive to treatment.3,4 the characteristic features of ga in histopathology consist of lymphohistiocytic infiltrate, degeneration of collagen, and mucin deposition.4 certolizumab pegol is a pegylated tumor necrosis factor alpha (tnf) antagonist commonly used as a treatment for various autioimmune diseases including psoriatic and rheumatoid arthritis.5 we report a case of a patient with generalized ga who was successfully treated with certolizumab. a 73-year-old woman presented to our clinic with multiple itchy red rashes on the trunk and extremities that were first noticed three years earlier. she had no other comorbidities, and her family medical history was unremarkable. upon physical examination, there were numerous erythematous annular papules and plaques on her trunk, arms, legs, and feet. the patient refused biopsy, however since her clinical presentation was very characteristic, we were pretty confident with our diagnosis. the patient was diagnosed with granuloma annulare and was previously prescribed topical treatments including potent topical corticosteroids and topical calcineurin inhibitors. however, lesions gradually increased in size and extent to involve her entire body, hence she was prescribed phototherapy with nbuvb. she introduction case report generalized granuloma annulare (ga) is a subtype of ga that consists of widespread annular papules and plaques varying in size. there are no randomized trials of treatment for ga, however topical treatment, phototherapy, and various systemic therapies, have been reported to be effective. we report the first case of generalized ga that is successfully treated with certolizumab pegol. abstract skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 273 underwent 28 sessions of phototherapy, but the skin lesions kept spreading. we then prescribed her adalimumab, which resulted in minor improvement. after four months with unsatisfactory result, we decided to treat her with certolizumab 400 mg every two weeks. by week eight of initiating certolizumab, we saw major clinical improvement. the patient was then instructed to continue treatment with certolizumab for another six months to prevent reoccurrence of ga. figure 1. patient at week 0 before certolizumab treatment generalized granuloma annulare (ga) is an extensive type of ga that consists of grouped of annular papules and plaques varying in sizes that can present anywhere on the body surface.1,3 histologically ga can show lymphohistiocytic infiltrates and collagen degeneration.2 furthermore, ga is considered a th1-type delayed hypersensitivity reaction.6 figure 2. patient at 12 weeks of certolizumab treatment tumor necrosis factor-alpha (tnf-) has also been known as an important cytokine in a granuloma formation, which is the logic behind the use of tnf- antagonists for ga.7 few studies have reported the successful treatment of ga using adalimumab and infliximab.7,8 we present the first case of a patient with generalized ga who failed topical treatment, phototherapy, and adalimumab, but was able to achieve complete resolution with certolizumab. certolizumab pegol is a pegylated fab portion of a human monoclonal antibody indicated for inflammatory and autoimmune diseases.5 it works by binding to and neutralizing tnf-, thereby reducing the elevated levels of tnf that propagate inflammation. in addition, pegylation serves to enhance its pharmacokinetic behavior to include improving solubility, drug stability and discussion skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 274 decreasing immunogenicity.9,10 although no studies exist on the efficacy of certolizumab on ga, the excellent response of this patient demonstrates that certolizumab may be an effective treatment for generalized ga. generalized granuloma annulare (ga) is often resistant to a variety of treatments and may take a chronic course. certolizumab can be an alternative treatment for persistent generalized ga. conflict of interest disclosures: none funding: none corresponding author: nahla shihab, md department of dermatology icahn school of medicine at mount sinai 5 e 98th street, ny, ny 10029 email: nahla.shihab@gmail.com references: 1. thornsberry la, english jc iii. etiology, diagnosis, and therapeutic management of granuloma annulare: an update. am j clin dermatol 2013;14(4):279–90 2. cyr pr. diagnosis and management of granuloma annulare. am fam physician. 2006;74(10):1729–34. 3. dabski k, winkelmann rk. generalized granuloma annulare: clinical and laboratory findings in 100 patients. j am acad dermatol. 1989;20(1):39–47. 4. schmieder sj, schmieder gj. granuloma annulare. statpearls. treasure island (fl)2019. 5. goel n, stephens s. certolizumab pegol. mabs. 2010;2(2):137-47. 6. chen a, truong ak, worswick s. the role of biologics in the treatment of chronic granuloma annulare. int j dermatol. 2019;58(5):622-26 7. bürgler c, vinay k, häfliger s, klötgen hw, yawalkar n. infliximab reduces activated myeloid dendritic cells, different macrophage subsets and cxcr3‐positive cells in granuloma annulare. 2019; j dermatol(epub). 8. min ms, lebwohl m. treatment of recalcitrant granuloma annulare (ga) with adalimumab: a single‐center, observational study. j am acad dermatol. 2016 jan;74(1):127-33. 9. cessak g, kuzawinska o, burda a, lis k, wojnar m, mirowska-guzel d, et al. tnf inhibitors mechanisms of action, approved and off-label indications. pharmacol rep. 2014;66(5):836-44. 10. schreiber s. certolizumab pegol for the treatment of crohn's disease. therap adv gastroenterol. 2011;4(6):375-89. conclusion mailto:nahla.shihab@gmail.com https://www-ncbi-nlm-nih-gov.eresources.mssm.edu/pubmed/?term=vinay%20k%5bauthor%5d&cauthor=true&cauthor_uid=31290564 https://www-ncbi-nlm-nih-gov.eresources.mssm.edu/pubmed/?term=h%c3%a4fliger%20s%5bauthor%5d&cauthor=true&cauthor_uid=31290564 https://www-ncbi-nlm-nih-gov.eresources.mssm.edu/pubmed/?term=kl%c3%b6tgen%20hw%5bauthor%5d&cauthor=true&cauthor_uid=31290564 https://www-ncbi-nlm-nih-gov.eresources.mssm.edu/pubmed/?term=kl%c3%b6tgen%20hw%5bauthor%5d&cauthor=true&cauthor_uid=31290564 https://www-ncbi-nlm-nih-gov.eresources.mssm.edu/pubmed/?term=yawalkar%20n%5bauthor%5d&cauthor=true&cauthor_uid=31290564 https://www-ncbi-nlm-nih-gov.eresources.mssm.edu/pubmed/?term=min+ms%2c+lebwohl+m.+treatment+of+recalcitrant+granuloma+annulare+(ga)+with+adalimumab%3a+a+single%e2%80%90center%2c+observational+study. https://www-ncbi-nlm-nih-gov.eresources.mssm.edu/pubmed/?term=min+ms%2c+lebwohl+m.+treatment+of+recalcitrant+granuloma+annulare+(ga)+with+adalimumab%3a+a+single%e2%80%90center%2c+observational+study. phase 1 study of fianlimab, a human lymphocyte activation gene-3 monoclonal antibody, in combination with cemiplimab in advanced melanoma: expansion cohort analysis omid hamid,1 karl lewis,2 amy weise,3 meredith mckean,4 kyriakos p papadopoulos,5 john crown,6 tae min kim,7 nehal j lakhani,8 john kaczmar,9 ragini kudchadkar,10 alexander spira,11 guilherme rabinowits,12 kevin kim,13 richard carvajal,14 stephen williamson,15 ella ioffe,16 shuquan chen,16 jayakumar mani,16 vladimir jankovic,16 laura brennan,16 glenn kroog,16 tasha sims,16* israel lowy,16 giuseppe gullo16 1the angeles clinical and research institute, a cedars-sinai affiliate, los angeles, ca, usa; 2university of colorado hospital, co, usa; 3henry ford hospital, detroit, mi, usa; 4sarah cannon research institute/tennessee oncology pllc, nashville, tn, usa; 5start san antonio, san antonio, tx, usa; 6st vincent’s university hospital, dublin, ireland; 7seoul national university hospital, seoul, south korea; 8start midwest, grand rapids, mi, usa; 9musc hollings cancer center, north charleston, sc, usa; 10emory university school of medicine, atlanta ga, usa; 11virginia cancer specialists, fairfax, va, usa; 12miami cancer institute, miami, fl, usa; 13sutter health research enterprise, san francisco, ca, usa; 14columbia university medical center, new york, ny, usa; 15university of kansas medical center, fairway, ks, usa; 16regeneron pharmaceuticals, inc., tarrytown, ny, usa *formerly with regeneron pharmaceuticals, inc. funding funding was provided by regeneron pharmaceuticals, inc. table 1. baseline characteristics and disposition: anti–pd-l1 naive (cohorts 6 + 15)† characteristic anti–pd-l1 naive† cohorts 6 + 15 (n=80)cohort 6 (n=40) cohort 15 (n=40) age median (range), years 69.5 (27–85) 69.0 (24–88) 69.0 (24–88) ≥65 years, % (n) 60.0 (24) 62.5 (25) 61.3 (49) male, % (n) 62.5 (25) 57.5 (23) 60.0 (48) white, % (n) 90.0 (36) 90.0 (36) 90.0 (72) sod of tl at baseline, median (range), mm 51 (15–214) 52 (11–173) 51.5 (11–214) braf mutant, % (n) 27.5 (11) 30.0 (12) 28.8 (23) melanoma subtype, % (n) acral 7.5 (3) 5.0 (2) 6.2 (5) mucosal 2.5 (1) 0 1.2 (1) cutaneous nonacral 90.0 (36) 95.0 (38) 92.5 (74) metastasis stage at baseline, % (n) m0 15.0 (6) 5.0 (2) 10.0 (8) m1 82.5 (33) 87.5 (35) 85.0 (68) m1c‡ 45.0 (18) 22.5 (9) 33.8 (27) ldh > uln, % (n) 42.5 (17) 27.5 (11) 35.0 (28) liver metastases, % (n) 35.0 (14) 12.5 (5) 23.8 (19) previous systemic therapy, % (n) 20.0 (8)§ 0 10.0 (8) †prior systemic therapies, including prior adjuvant therapies, excluded for cohort 15. ‡m1 category includes m1, m1a, m1b, and m1c. §two patients received prior treatment for advanced disease and six patients received prior adjuvant treatment. ldh, lactate dehydrogenase; pd-1, programmed cell death-1; pd-l1, programmed cell death-ligand 1; sod, sum of diameters; tl, target lesion; uln, upper limit of normal. table 2. tumor response among anti–pd-l1–naive patients (cohorts 6 + 15)† % (n), unless otherwise stated anti–pd-l1 naive† cohorts 6 + 15 (n=80)cohort 6 (n=40) cohort 15 (n=40) orr, % (95% ci) 62.5 (45.8, 77.3) 65 (48.3, 79.4) 63.8 (52.2, 74.2) complete response 15.0 (6) 2.5 (1) 8.8 (7) partial response 47.5 (19) 62.5 (25) 55.0 (44) stable disease 17.5 (7) 15.0 (6) 16.3 (13) progressive disease 15.0 (6) 15.0 (6) 15.0 (12) ne 5.0 (2) 5.0 (2) 5.0 (4) dcr 80.0 (32) 80.0 (32) 80.0 (64) km-estimated pfs, median (95% ci), months 24 (4.2, ne) nr (7.5, ne) 24 (9.9, ne) dor, median (95% ci), months nr (11.9, ne) nr (6.3, ne) nr (22.6, ne) orr: baseline ldh, n/n1 (%) ldh > uln 10/17 (58.8) 6/11 (54.5) 16/28 (57.1) ldh normal 15/23 (65.2) 18/24 (75.0) 33/47 (70.2) orr: liver metastasis, n/n2 (%) yes 6/14 (42.9) 3/5 (60.0) 9/19 (47.4) no 19/26 (73.1) 23/35 (65.7) 42/61 (68.9) †prior systemic therapies, including prior adjuvant therapies, excluded for cohort 15. ci, confidence interval; dcr, disease control rate; dor, duration of response; km, kaplan-meier; ldh, lactase dehydrogenase; n1, proportion of patients with the listed ldh status; n2, proportion of patients with the listed liver metastasis status; ne, not evaluable; nr, not reached; orr, objective response rate; pd-1, programmed cell death-1; pd-l1, programmed cell death-ligand 1; pfs, progression-free survival; uln, upper limit of normal. table 6. safety for anti–pd-l1–naive and –experienced patients % (n), unless otherwise stated anti–pd-l1 naive† (n=80) anti–pd-l1 experienced (n=15) duration of exposure, median (range), weeks 30.9 (2.0–110.0) 9.0 (6.0–57.0) patients with treatment-emergent aes regardless of attribution any grade grade 3–5 any grade grade 3–5 overall 96.3 (77) 40.0 (32) 80.0 (12) 46.7 (7) serious 28.8 (23) 25.0 (20) 33.3 (5) 26.7 (4) patients with treatment-related aes overall 80.0 (64) 20.0 (16) 53.3 (8) 20.0 (3) serious 13.8 (11) 13.8 (11) 13.3 (2) 13.3 (2) treatment-emergent immune-mediated aes, % (n) any grade grade 3–5 any grade grade 3–5 overall 65.0 (52) 11.3 (9) 33.3 (5) 13.3 (2) occurred in >5% of patients (any grade) rash 23.8 (19) 0 26.7 (4) 0 pruritis 15.0 (12) 0 0 0 hypothyroidism 13.8 (11) 0 0 0 arthralgia 12.5 (10) 0 6.7 (1) 0 diarrhea 12.5 (10) 0 13.3 (2) 0 myalgia 10.0 (8) 0 6.7 (1) 0 adrenal insufficiency 8.8 (7) 2.5 (2) 6.7 (1) 0 colitis 7.5 (6) 3.8 (3) 0 0 pneumonitis 6.3 (5) 0 6.7 (1) 6.7 (1) †prior systemic therapies, including prior adjuvant therapies, excluded for cohort 15. ae, adverse event; pd-1, programmed cell death-1; pd-l1, programmed cell death-ligand 1. table 3. patient disposition among anti–pd-l1–naive patients (cohorts 6 + 15)† % (n), unless otherwise stated anti–pd-l1 naive† cohorts 6 + 15 (n=80)cohort 6 (n=40) cohort 15 (n=40) patients completed planned treatment‡ 15.0 (6) 5.0 (2) 10.0 (8) ongoing treatment 15.0 (6) 52.5 (21) 33.8 (27) discontinued treatment 70.0 (28) 42.5 (17) 56.3 (45) disease progression 45.0 (18) 17.5 (7) 31.3 (25) ae 15.0 (6) 15.0 (6) 15.0 (12) patient decision 5.0 (2) 0 2.5 (2) death 2.5 (1) 5.0 (2) 3.8 (3) physician decision 2.5 (1) 5.0 (2) 3.8 (3) duration of exposure, median (range), weeks 37.1 (2–110) 24.2 (3–56) 30.9 (2–110) †prior systemic therapies, including prior adjuvant therapies, excluded for cohort 15. ‡planned treatment; 51 weeks + additional 51 weeks given based on investigator discretion. ae, adverse event; pd-1, programmed cell death-1; pd-l1, programmed cell death-ligand 1. table 5. clinical activity among anti–pd-l1–experienced patients (cohort 7) % (n), unless otherwise stated total (n=15) orr, % (95% ci) 13.3 (1.7, 40.5) complete response 0 partial response 13.3 (2) stable disease 26.7 (4) progressive disease 53.3 (8) ne 6.7 (1) dcr 40.0 (6) km-estimated pfs, median (95% ci), months 1.5 (1.3, 7.7) dor, median (95% ci), months nr (3.4, ne) orr by lag-3 expression, % <1% na ≥1% 18.2 orr by pd-l1 expression, % <1% 18.2 ≥1% 0 ci, confidence interval; dcr, disease control rate; dor, duration of response; km, kaplan-meier; lag-3, lymphocyte activation gene-3; na, not available; ne, not evaluable; nr, not reached; orr, objective response rate; pd-1, programmed cell death-1; pd-l1, programmed cell death-ligand 1; pfs, progression-free survival. table 4. clinical activity based on pd-l1 and lag-3 levels (cohort 6) patients, % (n) orr, % (n) pfs, median (95% ci), months overall 100.0 (40) 62.5 (25) 24 (4.2, ne) lag-3 expression ≥1% 67.5 (27) 74.1 (20) 24 (5.6, ne) lag-3 expression <1% 12.5 (5) 40.0 (2) nr (1.4, ne) pd-l1 expression ≥1% 45.0 (18) 77.8 (14) 24 (9.9, ne) pd-l1 expression <1% 40.0 (16) 56.3 (9) 8.5 (2.8, ne) pd-l1 ≥1% and lag-3 ≥1% 45.0 (18) 77.8 (14) 24 (9.9, ne) pd-l1 <1% and lag-3 ≥1% 22.5 (9) 66.7 (6) 5.6 (1.2, ne) pd-l1 <1% and lag-3 <1% 12.5 (5) 40.0 (2) nr (1.4, ne) there were no patients with pd-l1 ≥1% and lag-3 <1%. ci, confidence interval; ihc, immunohistochemistry; lag-3, lymphocyte activation gene-3; na, not available; ne, not evaluable; orr, objective response rate; pd-l1, programmed cell death-ligand 1; pfs, progression-free survival. results baseline demographics and disease characteristics • as of july 1, 2022, 40 patients were enrolled and received treatment in each cohort 6 and cohort 15, and 15 patients received treatment in cohort 7. • median age among the anti–pd-l1–naive patients (cohorts 6 + 15) was 69.0 years (range: 24–88), 60.0% of patients were male, and 90.0% were white (table 1). • for anti–pd-1/pd-l1–experienced patients (cohort 7), median age was 59.0 years, 46.7% were male, and 60.0% were white. • the median sum of diameters of the target lesion was 51.5 mm (range: 11–214) among patients in cohorts 6 + 15 (table 1). • among anti–pd-l1–naive patients 33.8% had stage m1c at baseline, 35% had lactate dehydrogenase (ldh) levels above the upper limit of normal (uln), and 23.8% had liver metastases (table 1). methods • adult patients with advanced melanoma who had no prior anti–pd-1/pd-l1 treatment (naive; cohort 6 and 15) or had prior anti–pd-1/pd–l1 treatment within 3 months of screening (experienced; cohort 7) received fianlimab 1600 mg + cemiplimab 350 mg intravenously (iv) every 3 weeks (q3w), for up to 51 weeks (figure 1). – prior systemic therapies, including prior adjuvant therapies, were excluded for cohort 15. – patients in cohort 7 must have tolerated prior anti–pd-1/pd-l1 therapy for at least 6 weeks and must not have discontinued treatment due to toxicity. – patients had an option to continue fianlimab + cemiplimab treatment for an additional 51 weeks. • tumor measurements were performed every 6 weeks for the first 24 weeks, then 9 weeks for the subsequent 27 weeks. • the data cut-off date was july 1, 2022. figure 2. efficacy overview among anti–pd-l1–naive patients (cohorts 6 + 15)† †prior systemic therapies, including prior adjuvant therapies, excluded for cohort 15. §patients with ongoing status (missing study complete status). ci, confidence interval; cr, complete response; dor, duration of response; ne, not estimable; nr, not reached; pd, progressive disease; pd-1, programmed cell death-1; pd-l1, programmed cell death-ligand 1; pfs, progression-free survival; pr, partial response; sd, stable disease; sod, sum of diameters. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 100 80 60 40 20 0 -20 -40 -60 -80 -100 pd sd pr cr b e s t p e rc e n t c h a n g e fr o m b a s e lin e patients (n=76) 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 100 80 60 40 20 0 -20 -40 -60 -80 -100 p e rc e n t o f s o d c h a n g e fr o m b a s e lin e months 0 total (cohorts 6 + 15) no. at risk: 2 4 6 8 10 12 14 16 18 20 22 24 26 28 3230 80 64 56 42 32 28 20 16 16 12 8 7 6 6 4 01 1.0 0.8 0.6 0.4 0.2 0 p ro b a b ili ty o f p ro g re s s io n -f re e s u rv iv a l months baseline on treatment (after 33 weeks) pd sd pr cr nr 76% of patients had any level of tumor reduction median dor not yet reached kaplan-meier estimation of pfs anti–pd-l1 naive † by investigator assessment (n=80) pfs, median (95% ci), months 24.0 (9.9, ne) estimated event-free probability at 12 months, % (95% ci) 55.0 (41.6, 66.5) figure 3. clinical activity among anti–pd-l1–experienced patients (cohort 7) §patients with ongoing status (missing study complete status). cr, complete response; pd, progressive disease; pd-1, programmed cell death-1; pr, partial response; sd, stable disease; sod, sum of diameters. 100 80 60 40 20 0 -20 -40 -60 -80 -100 pd sd pr b e s t p e rc e n t c h a n g e fr o m b a s e lin e 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 100 80 60 40 20 0 -20 -40 -60 -80 -100p e rc e n t o f s o d c h a n g e fr o m b a s e lin e months 1 2 3 4 5 6 7 8 9 10 11 12 13 14 patients (n=14) pd sd pr cr figure 1. study schema †prior systemic therapies, including prior adjuvant therapies, excluded for cohort 15. ‡defined as patients who had progressed on prior anti–pd-1/pd-l1 treatment within 3 months of screening. patients must have tolerated therapy for a ≥6 weeks and must not have discontinued treatment due to toxicity. §with an option for an additional 51 weeks. iiresponse assessments were every 6 weeks for the first 24 weeks, then 9 weeks for the subsequent 27 weeks. ada, antidrug antibody; ecog ps, eastern cooperative oncology group performance score; iv, intravenous; lag-3, lymphocyte activation gene-3; mab, monoclonal antibody; mhc, major histocompatibility complex; orr, objective response rate; pd-1, programmed cell death-1; pd-l1, programmed cell death-ligand 1; pd-l2, programmed cell death-ligand 2; pk, pharmacokinetics; recist 1.1, response evaluation criteria in solid tumors version 1.1. expansion cohorts 6 and 15† anti–pd-1/pd-l1 naive fianlimab 1600 mg + cemiplimab 350 mg iv every 3 weeks, for up to 51 weeks§ • tumor response assessed by investigators • response assessments every 6 or 9ii weeks (recist 1.1) to determine orr primary endpoint • orr per recist 1.1 criteria secondary endpoints • safety, pk, and ada key inclusion criteria • ≥18 years of age • ecog ps of 0 or 1 • at least one lesion measurable by recist 1.1 • metastatic or inoperable locally advanced nonuveal melanoma key exclusion criteria • prior treatment with lag-3–targeting biologic or small molecule • radiation therapy within 2 weeks prior to enrollment expansion cohort 7 anti–pd-1/pd-l1 experienced‡ objectives • to assess preliminary anti-tumor activity of fianlimab + cemiplimab as measured by orr per response evaluation criteria in solid tumors (recist) version 1.1 criteria in patients with advanced melanoma. • to assess the safety profile of fianlimab + cemiplimab in patients with advanced melanoma. key takeaway • this analysis provides additional data that supports the use of fianlimab + cemiplimab combination treatment for patients with advanced melanoma. conclusions • in two sequential expansion cohorts (total n=40/cohort), fianlimab + cemiplimab independently and reproducibly demonstrated clinically meaningful activity among patients with anti–pd-l1–naive advanced melanoma. – orr was 63.8% (7 complete responses and 44 partial responses) and median dor was not reached (95% ci: 22.6, ne). – kaplan-meier estimation of pfs was 24 months (95% ci: 9.9, ne). – clinical activity was observed in poor prognosis subgroups (i.e., ldh > uln, liver metastases), as well as in patients with high and low pd-l1 expression levels. • observed clinical activity in the anti–pd-l1–exposed population (orr 13.3%) was consistent with previous reports of anti–lag-3 + anti–pd-l1 combination treatment in this setting. • the fianlimab + cemiplimab combination demonstrated an acceptable risk/benefit profile similar to that observed with cemiplimab monotherapy and other anti–pd-1 agents. in the anti–pd-l1– naive population: – 96.3% of patients experienced treatment-emergent aes (teaes) of any grade. – 28.8% of patients experienced serious teaes. – 16.3% of patients discontinued treatment due to a teae. • a phase 3 trial (nct05352672) of fianlimab + cemiplimab in patients with advanced melanoma is ongoing. background • combination anti–lymphocyte activation gene-3 (lag-3) and anti–programmed cell death-1 (pd-1) treatment demonstrated higher median progression free survival (pfs) and objective response rate (orr) compared with anti–pd-1 monotherapy in a phase 2/3 clinical trial of patients with untreated advanced melanoma.1 • the relativity-047 study showed an orr of 43.1%.2 • fianlimab (regn3767) and cemiplimab are both high-affinity, human, hinge-stabilized immunoglobulin 4 (igg4) monoclonal antibodies derived using velocimmune technology. • fianlimab blocks lag-3 and major histocompatibility complex (mhc) class ii–driven t-cell inhibition.3 • cemiplimab blocks interactions of pd-1 with pd-ligand 1 (pd-l1) and pd-l2.4 • in an initial expansion cohort, fianlimab + cemiplimab in patients with advanced melanoma gave an impressive efficacy of >60% orr.5 • here we present clinical activity and safety follow-up data of fianlimab + cemiplimab in phase 1 expansion cohorts of patients with advanced melanoma, and a confirmatory expansion cohort (nct03005782). presented at winter clinical derm 2023, january 13–18, 2023 (encore of previous presentation at the european society of medical oncology [esmo] 2022, september 8–13, hamid o et al.). reused with permission. tumor response • the orr for anti–pd-l1–naive patients was 63.8% (95% confidence interval [ci]: 52.2, 74.2%; table 2). – seven (8.8%) patients had a complete response, and 44 (55.0%) patients had a partial response. • eight (10.0%) anti–pd-l1–naive patients completed planned treatment; 33.8% of patients are ongoing treatment, and 56.3% of patients discontinued treatment (table 3). • among anti–pd-l1–experienced patients, orr was 13.3% (95% ci: 1.7, 40.5); 2 (13.3%) patients had a partial response (table 5, figure 3). • the median kaplan-meier estimated pfs among anti–pd-l1 experienced patients was 1.5 months (95% ci: 1.3, 7.7) (table 5). • clinical activity based on pd-l1 and lag-3 levels was assessed for patients in cohort 6 (table 4). – formalin-fixed, paraffin-embedded baseline tumor samples were used to determine lag-3 and pd-l1 expression levels by ihc. – lag-3 levels were reported as the percentage of positively staining immune cells in the viable tumor area using the 17b4 clone. safety data • the safety profile of fianlimab + cemiplimab combination treatment was similar to anti–pd-l1 therapies. • median duration of treatment exposure was 30.9 weeks (range: 2–110) among anti–pd-l1–naive patients and 9.0 weeks (range: 6–57) among anti–pd-l1–experienced patients (table 6). • in the anti–pd-l1–naive population: – rate of grade ≥3 treatment-related adverse events (ae) was 20.0%. – rate of discontinuation due to treatment-related aes was 15.0%. – treatment-related aes leading to death occurred in two patients (2.5%): one experienced colitis and one experienced cardiac shock. – the patient who experienced cardiac shock also had covid-19 with pulmonary edema concurrently. – rate of treatment-emergent adrenal insufficiency was 10%. references 1. tawbi ha et al. n engl j med. 2022;386:24–34. 2. long gv et al. j clin oncol. 2022;40(suppl 36):360385. 3. burova e et al. mol cancer. 2019;18:2051–2062. 4. burova e et al. mol cancer. 2017;16:861–870. 5. hamid o et al. j clin oncol. 2021;39(suppl 15):9515. acknowledgments the authors thank the patients, their families, all other investigators and all investigational site members involved in this study. the study was funded by regeneron pharmaceuticals, inc., and sanofi. medical writing support and typesetting was provided by jenna lee, msc, of prime, knutsford, uk, funded by regeneron pharmaceuticals, inc., and sanofi. disclosure omid hamid reports honoraria from bristol-myers squibb, novartis, pfizer, sanofi and regeneron pharmaceuticals, inc.; and consulting or advisory roles with aduro biotech, akeso biopharma, amgen, arcus biosciences, bioatla, bristol-myers squibb, cytomx therapeutics, exelixis, genentech, glaxosmithkline, idera, immunocore, incyte, iovance biotherapeutics, merck, merck serono, moderna therapeutics, nextcure, novartis, pfizer, regeneron pharmaceuticals, inc., roche, sanofi, seattle genetics, torque and zelluna. scan the qr code for co-author disclosures skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 881 brief article oral jak inhibitor, upadacitinib use in treatment of pemphigus foliaceus sophie guénin msc1, syed shah, mbbs, mrcp, frcp2, mark g. lebwohl md1 1 the kimberly and eric j. waldman department of dermatology, icahn school of medicine at mount sinai hospital, new york, ny 2 university hospitals of morecambe bay, nhs foundation trust, uk. pemphigus foliaceus (pf) is a variant of pemphigus, a rare, blistering autoimmune condition.1 drugs and compounds known to contain thiol and phenol structures have also been reported to provoke pf. pf occurs when immunoglobulin g (igg) autoantibodies target intercellular adhesion glycoprotein desmoglein-1 (dsg-1) triggering the loss of intercellular connections between keratinocytes and subsequent subcorneal blister formation.1 patients most often present with flaccid, superficial vesicles and bullae of the skin on the scalp, chest, and back with mucosal sparing.1 biopsy of pf shows acantholysis at the granular layer of the epidermis and formation of vacuoles and/or subcorneal blisters within the intercellular spaces of the epidermis.1 there are few randomized controlled trials for pf. treatments are largely based in expert opinion, consensus and anecdotal evidence.2 to date, the mainstay treatment is systemic corticosteroids and rituximab (cd-20 inhibitor).2 other commonly used treatments include mycophenolate mofetil (mmf), azathioprine, high dose intravenous immunoglobulins, and cyclophosphamide.2 more recently, janus kinase (jak) inhibitors have become increasingly used in a variety of autoimmune conditions.3 upadacitinib is a jak1-specific inhibitor which has been approved for psoriatic arthritis, rheumatoid arthritis, ulcerative colitis, atopic dermatitis, abstract pemphigus foliaceus (pf) is a rare, blistering autoimmune condition that occurs when desmoglein-1 autoantibodies target and lead to loss of intercellular connections, resulting in blister formation on the skin. current standard of care consists of highly immunosuppressive therapies such as prednisone, rituximab, and mycophenolate mofetil. a 43-year-old male with new-onset pf was treated with upadacitinib, a jak inhibitor. he saw resolution of his blisters within 12 weeks of treatment and remains in remission from his pf. our case demonstrates that jak inhibition may prove to be an effective strategy in preventing dsg-1-triggered blisters. jak1 inhibitors also may prove to be a safer, less immunosuppressive alternative to the highly immunosuppressive agents available today. larger studies will be required to study the drug’s efficacy in others with pf. introduction skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 882 and ankylosing spondylitis.4 upadacitinib has also shown efficacy in treatment of psoriasis and eczema overlap condition, psema.5 herein, we detail a case of 43-year-old male with severe pemphigus foliaceus which responded to an oral jak inhibitor, upadacitinib. a 43-year-old male with no significant past medical history presented with a four-month history of a scaly, erythematous pruritic rash consisting of plaques and papules that originated on his head and spread to his chest and scalp. the patient denied any recent changes in medication or medical condition prior to rash presentation. he lived in the middle east and his work involved frequent exposure to fragrances. at this time, the differential diagnosis included pf. a biopsy of the patient’s chest was performed and sent for hematoxylin & eosin staining (h&e) and direct immunofluorescence (if). however, the biopsy revealed only spongiotic dermatitis consistent with a contact dermatitis or other eczematous reaction and direct if failed to show staining for igm, igg, iga, c3 or fibrinogen. given the patient’s spongiotic dermatitis biopsy and psoriasiform lesions, he was started on a course of topical corticosteroids and topical roflumilast for suspected psema. despite treatment, over the next month, the patient’s condition continued to progress. he continued to develop eczematous, pruritic papules and patches until finally presenting with widespread, erythematous scaly, exfoliative lesions with desquamation and bullae (figure 1a, figure 2a). the patient was started on 60 mg of prednisone; however, he failed to respond within the first week. thus, he was switched to upadacitinib 15mg daily, to treat suspected, severe, psema, a condition which we have successfully treated with jak inhibitors5. given the unusual progression of disease, the patient underwent serum testing for dsg1 and dsg-3, which returned positive for dsg1 (>200 ru/ml). shortly thereafter, a second biopsy revealed subcorneal blisters with neutrophils and positive direct intercellular if for igg and c3, which were consistent with pemphigus foliaceus (fig 3). antinuclear antibodies were negative. within one week, the patient saw rapid improvement in his itch and blisters on 15mg of upadacitnib; thus, the patient deferred the start of rituximab treatment for biopsyconfirmed pf. the following week, he was increased to 30mg daily for continued control of a few, newly developed blisters. within two weeks of daily 30mg upadacitinib, the patient saw great improvement in his blisters and ceased forming new bullae. by week 12 of 30mg daily upadacitinib treatment, he was left with only residual hyperpigmentation at sites of his lesions (figure 1b, figure 2b). our patient’s rapid response to upadacitinib, a selective jak1 inhibitor, suggests a novel, steroid-sparing agent for pf treatment. while pf may occur spontaneously in genetically predisposed individuals, our patient’s pf could have been triggered by his repeat exposures to phenol-containing fragrances, such as vanillin. phenol-containing compounds disrupt the cellular adhesion mechanisms by stimulating release of proinflammatory cytokines from keratinocytes that lead to complement and case report discussion skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 883 figure 1. (a) torso of 43-year-old male with pemphigus foliaceous prior to upadacitinib treatment. (b) of 43-year-old male with pemphigus foliaceus after 12 weeks of upadacitinib 30mg qd treatment. figure 2. (a) back of 43-year-old male with pemphigus foliaceus prior to upadacitinib treatment. (b) back of 43-year-old male with pemphigus foliaceus after 12 weeks of upadacitinib 30g qd treatment. a b a b skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 884 figure 3. (a) subcorneal blisters with acantholysis. (b) within the dermis there is a dense chronic inflammatory infiltrate with occasional eosinophils. protease activation and subsequent acantholysis.6 drug or compound-induced pf blisters likely result from both biochemical and immunologic phenomena. while phenol exposures may have triggered our patient’s pf, he had also developed dsg1 antibodies, which play an important role in disease progression. dsg1 antibodies result in autoantibody-triggered signaling events that further promote keratinocyte dissociation.7 pemphigus has been largely considered a t helper (th) 2-dominant disease with predominance of th2 cytokines such as il-4 in pf patients. il-4 activates jak1 and results in increased th2 differentiation, activation of anti-dsg1-producing b cells, and downstream cytokine signaling that result in blister formation.8,9 thus, blocking jak1 activation may prove to be an effective strategy in blocking the signaling cascade that leads to pf. our patient’s rapid pf remission suggests that upadacitinib may be a novel therapeutic option for pemphigus patients. the oral jak1 inhibitor would offer a safer, more practical alternative to current treatments which consist of long-term corticosteroid use and intravenous rituximab treatments. further studies will be required to evaluate the efficacy of the treatment in a larger population. patient consent: consent for publication of all patient photographs and medical information was obtained by patient prior to article submission. the patient in this case report gave consent for their photographs and medication information to be published in print and online and with the understanding this information may be publicly available. conflict of interest disclosures: none funding: none corresponding author: sophie h. guénin, msc department of dermatology, icahn school of medicine at mount sinai hospital, 5 east 98th street, 5th floor, new york, ny 10029. email: sophiehelene.guenin@gmail.com references: 1. james, k. a., culton, d. a., & diaz, l. a. (2011). diagnosis and clinical features of pemphigus foliaceus. dermatologic clinics, 29(3), 405-412. conclusion a b skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 885 2. murrell, d. f., peña, s., joly, p., marinovic, b., hashimoto, t., diaz, l. a., ... & werth, v. p. (2020). diagnosis and management of pemphigus: recommendations of an international panel of experts. journal of the american academy of dermatology, 82(3), 575585. 3. hu, x., li, j., fu, m., zhao, x., & wang, w. (2021). the jak/stat signaling pathway: from bench to clinic. signal transduction and targeted therapy, 6(1), 402. 4. ferreira, s., guttman-yassky, e., & torres, t. (2020). selective jak1 inhibitors for the treatment of atopic dermatitis: focus on upadacitinib and abrocitinib. american journal of clinical dermatology, 21, 783-798. 5. abramovits w, cockerell c, stevenson lc, goldstein am, ehrig t, menter a. psema--a hitherto unnamed dermatologic entity with clinical features of both psoriasis and eczema. skinmed. 2005 sep-oct;4(5):275-81. doi: 10.1111/j.15409740.2005.03636.x. pmid: 16282748. 6. pile, h. d., yarrarapu, s. n. s., & crane, j. s. (2021). drug induced pemphigus. in statpearls [internet]. statpearls publishing. 7. waschke, j., bruggeman, p., baumgartner, w., zillikens, d., & drenckhahn, d. (2005). pemphigus foliaceus igg causes dissociation of desmoglein 1–containing junctions without blocking desmoglein 1 transinteraction. the journal of clinical investigation, 115(11), 31573165. 8. tavakolpour, s., & tavakolpour, v. (2016). interleukin 4 inhibition as a potential therapeutic in pemphigus. cytokine, 77, 189-195. 9. walter, e., vielmuth, f., rotkopf, l., sárdy, m., horváth, o. n., goebeler, m., ... & waschke, j. (2017). different signaling patterns contribute to loss of keratinocyte cohesion dependent on autoantibody profile in pemphigus. scientific reports, 7(1), 3579. skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 294 short communications superficial acral fibromyxoma with ossification on the fingertip christina avila, mph1, nima milani-nejad, md, phd2, david r. carr, md2 1the ohio state university college of medicine, columbus, oh 2the ohio state university department of internal medicine, division of dermatology, columbus, oh superficial acral fibromyxomas (safm) are soft tissue tumors with a predilection for the extremities that often involve the nail bed. secondary changes such as ossification and cartilaginous metaplasia are rarely reported.1,2 here we present a unique case of safm with ossification. a 19-year-old woman was referred to our clinic with a painful growth on the distal nailbed of her right third finger (figure 1). the lesion had been present for a year without any trauma. it was previously treated with cryotherapy and electrocautery for a clinical diagnosis of verruca without any improvement. physical examination showed a firm tender skin-colored keratotic papule located on the medial aspect of the distal subungual region of the third finger. an x-ray of the finger revealed a well-circumscribed 13 x 5 mm ossified mass in the subungual region of the distal fingertip without involvement of the underlying bone. she underwent surgical excision of the lesion with histopathology showing fibroblast-derived spindle and stellate-shaped cells suspended in a myxoid stroma without significant nuclear atypia or mitotic figures (figure 2a) and ossification (figure 2b). immunostaining showed tumor cells that were weakly positive for antismooth muscle actin and negative for cd34 and s100. the constellation of findings was consistent with diagnosis of safm. figure 1. hyperkeratotic papule in the distal subungual area of the third finger safm is a rare tumor that often involves the nail bed sometimes after trauma, but most patients report no inciting factor.3,4 potential complications include nail disfigurement, ulceration, pain, repeated trauma, and infections.3 however, most safm are asymptomatic. it presents as a solitary fleshcolored papule or nodule extending through the dermis with possible extension to underlying subcutaneous tissue, fascia, and periosteum.3,5 metastasis has never been reported, however mass effect can cause local bone erosion and lytic lesions. osseous skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 295 figure 2. (a) representative view (h&e, 40x) of removed tissue showing a well-circumscribed collection of uniform spindle-shaped cells without significant atypia, changes consistent with safm. (b) magnification (h&e, 100x) demonstrating ossification metaplasia, as was seen in our patient, has only been reported once before in the literature.2 safm should be kept in mind for masses on the distal extremities especially when there is nailbed involvement. the differential of safm includes ossifying fibromyxoid tumor, myxoid dermatofibrosarcoma protuberans, digital fibroma, and verruca vulgaris. microscopic examination typically shows fibroblast-like stellate and spindle-shaped cells arranged in a random, loose storiform or fascicular growth pattern suspended in a myxoid stroma with varying amounts of collagen.3,4 increased vasculature is often noted, and mast cells and giant multinucleated cells may be present.6 necrosis and formation of calcifications has been reported. nuclear atypia and mitotic figures are rare, if present. immunohistochemistry will show an safm pattern positive for cd34 and negative for s100. deviation from this pattern can occur, and similar to our patient, cd34-negative safm occur in 27-31%.2,3,5 additional helpful markers for safm that are often positive include cd99, vimentin, and epithelial membrane antigen and anti-smooth muscle actin is typically negative.3,5 management of safm should be based on location, size, involvement of underlying structures, atypical features, and associated complications. definitive treatment of safm is complete surgical excision. conflict of interest disclosures: none funding: none corresponding author: david r. carr, md the ohio state university college of medicine division of dermatology 540 officenter place, suite 240 columbus, oh 43230 phone: 614-293-1707 email: david.carr@osumc.edu references: 1. moulonguet i, biaggi a, eschard c, et al. plaquelike myofibroblastic tumor: report of 4 cases. am j dermatopathol. 2017;39(10):767–772. 2. chae jb, jo g, & mun jh. superficial acral fibromyxoma with bony change: successful treatment with en bloc nail excision using a fullthickness skin graft. int. j. dermatol. 2018;57(8):998–100. 3. hollmann tj, bovée jv, & fletcher cd. digital fibromyxoma (superficial acral fibromyxoma). mailto:david.carr@osumc.edu skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 296 am. j. surg. pathol. 2012;36(6):789-98 4. prescott rj, husain ea, abdellaoui a, et al. superficial acral fibromyxoma: a clinicopathological study of new 41 cases from the u.k.: should myxoma (nos) and fibroma (nos) continue as part of 21st-century reporting? br. j. dermatol. 2008;159(6):1315-21. 5. cullen d, diaz recuero jl, cullen r, et al. superficial acral fibromyxoma: report of 13 cases with new immunohistochemical findings. am. j. dermatopathol. 2017;39(1):14-22. 6. ashby-richardson h, rogers gs, & stadecker mj. superficial acral fibromyxoma: an overview. archives of pathology and laboratory medicine. 2011;135(8):1064-66. powerpoint presentation n= 171 p=0.02 differentiation uncertainty cohort 0% 0 20% 40% 80% 100% 60% 1 2 3 4 5 time (years) p ro b a b il it y class 1 class 2b class 2a › for clinicians who follow bwh staging, uncertainty in differentiation status may impact patient management. › the 40-gep provides objective and reproducible prognostic information, including in situations where the distinction between poorly and moderately differentiated histological grading is challenging. › within this cohort of high-risk cscc patients, whose bwh stage would change solely due to an alteration in differentiation status, the 40-gep was able to significantly stratify risk of metastasis. › incorporating the personalized 40-gep test results into clinical cscc risk assessment could enhance current patient management decisions, therefore improving patient outcomes. incorporating the 40-gene expression profile (40-gep) test for poorly differentiated cutaneous squamous cell carcinoma (cscc) tumors mitigates risk assessment uncertainty from histologic grading aaron s. farberg, md1; jennifer j. siegel, phd2; sarah j. kurley, phd2; alison l. fitzgerald, phd2; anesh prasai, phd2; matthew s. goldberg, md2,3; sherrif ibrahim, md4; sarah i. estrada, md5 1baylor scott & white health system, dallas, tx; 2castle biosciences inc., friendswood, tx; 3icahn school of medicine, new york city, ny 4university of rochester, rochester, ny; 5affiliated dermatology, scottsdale, az background › with 1.8 million new cases diagnosed each year, cutaneous squamous cell carcinoma (cscc) is the second most prevalent skin cancer in the u.s.1 while >95% of cscc cases are cured by surgery, an estimated 5% progress to nodal or distant metastasis, where survival rates drop to 50-83% and <40%, respectively.2,3 › the degree of differentiation plays a critical role in the progression of cscc. multiple studies have established poorly differentiated histology as an independent predictor of poor outcomes.2,4,5 › for patients with primary cscc and one or more risk factors, the clinically available 40-gep test accurately classifies likelihood of regional, nodal, or distant metastasis at 3 years post diagnosis (class 1=low risk, class 2a=moderate risk, class 2b= high risk).1,2 the 40-gep has also demonstrated independent and additive prognostic value in a multivariate model when compared to commonly utilized high-risk factors or brigham and women’s hospital (bwh) staging system (table 1).6,7 this study was sponsored by castle biosciences, inc. (cbi), which provided funding to the contributing centers for tissue and clinical data retrieval. jjs, sjk, alf, ap, and msg are employees and options holders of cbi. asf is a consultant for cbi. sie is an independent dermatopathologist contractor for cbi. methods references 1. skincancer.org, 2022 2. schmults, et al. jama derm 2013 3. nccn v2.2022 4. thompson, et al. jama derm 2016 5. karia, et al. jco 2014 6. wysong, et al. jaad 2021 7. ibrahim, et al. future onc. 2021 8. patel, et al. cancer medicine 2022 9. jagdeo, et al. jaad 2007 10. prezzano, et al. derm surg 2021 results for more information: aaron.farberg@gmail.com conclusions disclosures table 2. differentiation status was altered for 40% of the cohort, impacting bwh stage and potentially treatment decisionsclinical issue and objective there is a lack of widely accepted criteria for grading of cscc tumor tissue. this has led to subjectivity when determining differentiation status, complicated by different specialties’ usage of different staging criteria.8 multiple studies have shown concordance for cscc histologic grading is overall weak, especially when comparing moderately differentiated tumors.9,10 the inconsistency in the assessment of this risk factor can adversely impact its value as a prognostic factor due to its direct impact on clinicopathologic tumor staging.9 the objective of this study was to evaluate the ability of the 40-gep to risk stratify among a high-risk cscc “differentiation uncertainty cohort” and its impact on staging, therefore its potential to influence treatment decisions. a) risk factors comprising the brigham and women’s hospital (bwh) staging system.5 b) overall, 40% of the high-risk cscc cohort would change differentiation status, with 77.2% being upstaged and 22.8% being downstaged by bwh criteria. this ‘differentiation uncertainty cohort’ is representative of how inconsistencies in assessment of cscc tissue grading can directly impact staging and potentially treatment decisions. within the ‘differentiation uncertainty cohort’ (n=171), kaplan-meier survival analysis demonstrated statistically significant 3-year metastasis-free survival between all 40-gep classes. assessment of number of samples with metastatic outcomes was also evaluated and arranged by 40-gep class. table 1. independent risk assessment by the 40-gep complements existing systems7 40-gep risk class 3year mfs (95% ci) overall event rate non-metastatic (n) metastatic (n) class 1 90.1% (97.3-83.5%) 11.3% 63 8 class 2a 78.6% (87.9-70.3%) 21.4% 66 18 class 2b 62.5% (91.4-42.8%) 37.5% 10 6 without 40-gep 81.9% (87.9-76.3%) 18.7% 139 32 bwh t-stage t1 t2 t3 0 high risk factors t2a: 1 high risk factors t2b: 2-3 high risk factors 4 high risk factors high-risk factors • poorly differentiated histology • tumor diameter ≥2cm • perineural invasion ≥0.1mm • deep tumor invasion (beyond subcutaneous fat but excluding bone invasion, which qualifies as t3) calculate percentage of cases that incur a bwh stage change kaplan-meier survival analysis at 3 years post diagnosis number of patients upstaged bwh t-stage n t1 t2a 76 t2a t2b 55 t2b t3 1 total 132 number of patients downstaged t2a t1 22 t2b t2a 17 total 39 poorly or moderately differentiated tumors “differentiation uncertainty cohort” (n=171) modeled to opposing differentiation status figure 2. the 40-gep stratifies risk among a histologically ambiguous high-risk cscc cohort figure 1. development of a ‘differentiation uncertainty cohort‘ high-risk cscc cohort (n=420) multivariate cox regression risk factor n hazard ratio p value 40-gep result class 1 212 1.00 --class 2a 185 2.33 0.013 class 2b 23 6.86 <0.001 clinicopathologic risk factors poor differentiation 58 2.29 0.011 perineural invasion 53 1.22 ns deep invasion 72 2.05 0.039 tumor diameter n/a 1.07 ns immunosuppression 103 ----40-gep result class 1 212 1.00 --class 2a 185 2.98 <0.001 class 2b 23 9.42 <0.001 bwh t-stage t1/t2a 364 1.00 --t2b/t3 56 2.38 0.002 ➢class 2a result has similar risk to wellestablished high-risk factors ➢class 2b result 3-4x as risky as high-risk clinicopathologic factors or t-stage a) b) › a high-risk cscc cohort7 (n=420) was divided into moderately and poorly differentiated statuses based on clinical pathology reports and by an independent dermatopathologist review. if differentiation status differed between the report and the independent review, poorly differentiated was chosen as the status. the “differentiation uncertainty cohort” (n=171) was then staged by bwh criteria (table 2a). to represent the subjectivity and inconsistent evaluation that commonly happens with this risk factor, differentiation status was manually changed to the opposing status (i.e., poorly changed to moderately, moderately changed to poorly). determination of changes to bwh staging were documented to then note wherein changes of management may occur. kaplan-meier analysis was used to determine statistical significance of metastasis free survival (mfs) when incorporating the 40-gep test. = staged by bwh criteria scan here for more info presented at winter clinical dermatology conferences: january 13-18, 2023, kohala coast, hawaii and february 17-20, 2023, miami, fl m e ta s ta s is -f re e s u rv iv a l originally published in ibrahim et al. 2021 https://castlebiosciences.com/research-development/publications/ slide 1 investor presentation efficacy of red-light photodynamic therapy with 10% ala gel in relation to the epidermal extent of atypical keratinocytes in actinic keratosis retrospective exploratory analysis of three pivotal phase iii trials authors: e. bierhoff1, j.l. cohen2, r.-m. szeimies3, u. reinhold4, t. dirschka5 references [1] olsen ea, abernethy ml, kulp-shorten c, et al., j am acad dermatol 1991;24(5 pt 1):738–43. pubmed pmid: 1869646; [2] schmitz l, kahl p, majores m, et al., j eur acad dermatol venereol. 2016 aug;30(8):1303-7. pmid: 26955898 [3] roewert-huber j, patel mj, forschner t, et al., br j dermatol 2007;156 suppl 3:8–12. pubmed pmid: 17488400. [4] cockerell cj. j am. acad. dermatol 2000;42(1 pt 2):11–7. pubmed pmid: 10607351. [5] clinical study report (ala-ak-ct002), study design and results can be accessed via clinicaltrials.gov, see qr-code [6] clinical study report (ala-ak-ct003), study design and results can be accessed via clinicaltrials.gov, see qr-code [7] clinical study report (ala-ak-ct007), study design and results can be accessed via clinicaltrials.gov, see qr-code [8] ameluz® (prescribing information). woburn, ma: biofrontera inc.; 2021. [9] maisch t, santarelli f, schreml s, et al., exp dermatol. 2010; aug;19(8):e302-5. doi: 10.1111/j.1600-0625.2009.01001.x. pmid: 19845760. methods • retrospective analysis • three pivotal phase iii studies (ala-ak-ct002, -003 and -007 [5-7]) • histological and clinical data from a total of 762 lesions • punch biopsy at the screening visit • treatment scheme: • 3 h incubation of either 10% ala gel, mal or vehicle • illumination with broador narrow-spectrum red-light lamp • clinical clearance assessed 12 weeks after the last pdt for this exploratory analysis, lesion clearance was evaluated in relation to the kin grade of each respective lesion at the screening visit. red-light pdt appears to be an effective treatment option for ak regardless of the extend of epidermal keratinocyte atypia. ak lesion clearance rates when using red-light pdt with 10% ala gel or mal does not seem to depend on kin grades (i-iii). this exploratory analysis also suggests a higher efficacy of 10% ala gel compared to mal for all kin grades, which is consistent with the better penetration of 10% ala gel. this study is sponsored by biofrontera bioscience gmbh (germany). k in i ii k in i i k in i atypical keratinocytes in the lowest third of the epidermis figure 1a: histological classification according to cockerell [4] results lesion clearance rates (pdt with narrow-spectrum red-light led lamp) • 10% ala gel: kin i: 100%, kin ii: 98.1%, kin iii: 94.7% • mal: kin i: 92.9%, kin ii: 90.2%, kin iii: 87.5% data for pdt with 10% ala gel suggest higher clearance rates for all kin grades compared to pdt with mal (see figure 1b). one limitation of the study is the small number of lesions in some subgroups. 10% ala gel not clearedcleared mal vehicle not clearedcleared not clearedcleared not clearedcleared not clearedcleared not clearedcleared not clearedcleared not clearedcleared not clearedcleared not clearedcleared not clearedcleared not clearedcleared k in i ii k in i i to ta l ( k in i -i ii ) k in i 30 2 252 22 13 1 29 4 341 34 17 0 synopsis actinic keratosis (ak) • precancerous epidermal lesions • predominantly found in chronically sun exposed skin areas assessment • clinically (common): thickness and hyperkeratotic status, mild, moderate, or severe (acc. to olsen [1]) ! but: clinical classification is not a conclusive indicator of extent of atypical keratinocytes [1-3] • histologically: e.g. keratinocyte intraepithelial neoplasia (kin) grading (acc. to cockerell [4]), see figure 1a treatment • e.g. red-light photodynamic therapy (pdt) with 10% 5-aminolevulinic acid (ala) gel or methyl aminolevulinate (mal) cream (not available in us) 98 19 11 3 139 30 155 3 18 1 203 4 figure 1b: ak lesion clearance rates by treatment and kin grade each bar represents the percentage of ak lesions cleared/not cleared with the respective photosensitizing prodrug (10% ala gel, mal) or vehicle and red-light illumination, with color code indicating lamp type: the numbers adjacent to the bars correspond to the number of ak lesions considered for the respective subgroup (n). * the three lesions were located on the face/ forehead and were illuminated with the omnilux lamp; one was of mild and two were of moderate severity. 144 30 83 9 62 21 24 5 14 2 10 3 198 38 110 12 89 24 60 8 30 0 30 8 13 18 6 13 7 3 33 60 17 37 15 23 6 8 3* 0 3 8 52 86 26 50 25 34 ep id er m is ep id er m is ep id er m is d er m is d er m is d er m is atypical keratinocytes in the lowest two thirds of the epidermis full thickness atypia 87.9% 92% 88.2% 90.9% 93.8% 82.8% 82.8% 83.9% 42.9% 78.9% 83.8% 78.6% 82.2% 100% 74.9% 76.9% 78.8% 70% 39.5% 100% 98.1% 94.7% 97.1% 92.9% 90.2% 87.5% 89.4% 100% affiliations: 1 mvz corius dermpathbonn gmbh, heinz-werner-seifert-institute of dermatopathology bonn, germany; 2aboutskin dermatology and aboutskin research, greenwood village and lone tree, co, usa; 3department of dermatology and allergology, klinikum vest gmbh, recklinghausen, germany; 4mvz dermatologisches zentrum bonn gmbh, bonn, germany; 5centroderm gmbh, wuppertal, germany and faculty of health, university witten-herdecke, witten, germany total broad-spectrum red-light lamp narrow-spectrum red-light led lamp objective the aim was to evaluate if the effectiveness of red-light photodynamic therapy (pdt) for treating ak was influenced by the epidermal extent of keratinocyte atypia. the nanoemulsion-based 5-aminolevulinic acid gel (ameluz®; 10% ala gel) in combination with a specific narrow-spectrum red-light led lamp (bf-rhodoled® and rhodoled® xl) is fda-approved for lesionand fielddirected treatment of mild-to-moderate aks on the face/scalp [8]. one key advantage of the 10% ala gel formulation (compared to e.g. mal): deeper epidermal penetration [9]. what is the 10% ala gel? conclusion ? ala-ak-ct002 ala-ak-ct003 ala-ak-ct007 27.3% 35.5% 31.5% 41.9% 31.6% 37.7% 42.4% 31% long-term efficacy and safety of brodalumab in patients with psoriasis disease duration <10 and ≥10 years: analysis of two phase 3 studies benjamin ehst,1 george han,2 scott guenthner,3 kimberly eads,4 abby jacobson5 1oregon medical research center, portland, or; 2icahn school of medicine at mount sinai, new york, ny; 3the dermatology center of indiana, plainfield, in; 4the indiana clinical trials center, pc, plainfield, in; 5ortho dermatologics (a division of bausch health us, llc), bridgewater, nj 39th annual fall clinical dermatology conference® for dermatologists • october 17-20, 2019 • las vegas, nv introduction • brodalumab is a fully human anti–interleukin-17 receptor a monoclonal antibody that is efficacious in treating moderate-tosevere plaque psoriasis1 • evidence from studies of other biologics indicates that shorter disease duration may predict higher skin clearance rates objective • to characterize the relationship between psoriasis duration and brodalumab efficacy and safety methods • data were derived from two phase 3, multicenter, randomized clinical trials (amagine-2/-3)2 • in both studies, patients with moderate-to-severe plaque psoriasis were initially randomized to brodalumab every 2 weeks (q2w), ustekinumab, or placebo • at week 52, all patients entered the long-term extension and received brodalumab • in this post hoc analysis, skin clearance was assessed by 75% and 100% improvement in psoriasis area and severity index from baseline (pasi 75 and pasi 100, respectively) responses for patients who received any dose of brodalumab during the study and those who received continuous brodalumab 210 mg q2w through week 120 • patients were stratified by psoriasis duration at baseline (<10 years and ≥10 years) • safety was summarized by exposure-adjusted rates of treatmentemergent adverse events (teaes) for patients in both groups results efficacy • overall, 72.8% of patients receiving any dose of brodalumab (n=3625) and 70.8% receiving continuous brodalumab 210 mg q2w (n=339) had disease duration ≥10 years • in an observed analysis at week 52, for patients receiving any dose of brodalumab, 91.6% with disease duration ≥10 years and 92.4% with disease duration <10 years achieved pasi 75 (figure 1a) – pasi 75 response rates for patients receiving continuous brodalumab 210 mg q2w were similar (≥10 years, 93.5%; <10 years, 94.4%; figure 1b) • at 120 weeks, patients receiving any dose of brodalumab and those receiving continuous brodalumab 210 mg q2w achieved similar rates of pasi 75 response regardless of disease duration (figure 1) • observed pasi 100 responses at week 52 for patients with disease duration ≥10 years and <10 years were 54.0% and 54.4%, respectively, for patients receiving any dose of brodalumab and 62.7% and 65.2%, respectively, for patients receiving continuous brodalumab 210 mg q2w (figure 2) • at week 120, 58.3% of patients receiving any dose of brodalumab with disease duration ≥10 years and 57.3% of patients with disease duration <10 years achieved pasi 100 (figure 2) – pasi 100 response rates for patients receiving continuous brodalumab 210 mg q2w were similar at week 120 (disease duration ≥10 years, 65.4%; disease duration <10 years, 52.0%) safety • for all study years, slightly higher rates of teaes were observed in those with disease duration ≥10 years compared with disease duration <10 years (table 1) – the rate of serious adverse events was similar between subgroups acknowledgments: this study was sponsored by ortho dermatologics. medical writing support was provided by medthink scicom and funded by ortho dermatologics. ortho dermatologics is a division of bausch health us, llc. references: 1. siliq [package insert]. valeant pharmaceuticals north america llc; 2017. 2. lebwohl et al. n engl j med. 2015;373:1318-1328. conclusion • brodalumab is efficacious and well tolerated in patients with moderate-to-severe psoriasis regardless of disease duration © 2019. all rights reserved. 12 24 36 52 72 84 96 108 1200 92.4 90.2 91.6 89.2 0 20 40 60 80 100 r es po nd er s, % weeks weeks duration of disease <10 years duration of disease ≥10 years duration of disease <10 years duration of disease ≥10 years n1= 984 953 895 879 788 819 803 774 682 490 n1= 2640 2591 2457 2413 2225 2280 2230 2179 1915 1339 pasi 75: any dose of brodalumab 94.4 82.0 93.5 91.3 0 20 40 60 80 100 r es po nd er s, % n1= 99 99 94 90 89 89 87 83 73 50 n1= 240 240 224 218 201 208 200 201 172 127 pasi 75: continuous brodalumab 210 mg q2w a b 12 24 36 52 72 84 96 108 1200 figure 1. pasi 75 responses through week 120 in patients who received (a) any dose of brodalumab or (b) continuous brodalumab 210 mg q2w by disease duration subgroup. observed data analysis. error bars are the 95% confidence interval. n1, number of patients who had a valid measurement at the specified week; pasi 75, psoriasis area and severity index 75% improvement; q2w, every 2 weeks. 12 24 36 52 72 84 96 108 1200 12 24 36 52 72 84 96 108 1200 54.4 57.354.0 58.3 0 20 40 60 80 100 r es po nd er s, % n1= 984 953 895 879 788 819 803 774 682 490 n1= 2640 2591 2457 2413 2225 2280 2230 2179 1915 1339 pasi 100: any dose of brodalumab 65.2 52.0 62.7 65.4 0 20 40 60 80 100 r es po nd er s, % n1= 99 99 94 90 89 89 87 83 73 50 n1= 240 240 224 218 201 208 200 201 172 127 pasi 100: continuous brodalumab 210 mg q2w duration of disease <10 years duration of disease ≥10 years duration of disease <10 years duration of disease ≥10 years a b weeks weeks figure 2. pasi 100 responses through week 120 in patients who received (a) any dose of brodalumab or (b) continuous brodalumab 210 mg q2w by disease duration subgroup. observed data analysis. error bars are the 95% confidence interval. n1, number of patients who had a valid measurement at the specified week; pasi 100, psoriasis area and severity index 100% improvement; q2w, every 2 weeks. table 1. exposure-adjusted rates of teaes in patients who received ≥1 dose of brodalumab preferred term, n (exposure-adjusted event rate per 100 patient-years) duration of psoriasis <10 years (n=984; 1742.5 py) ≥10 years (n=2640; 4787.0 py) all teaes 4836 (277.5) 14,764 (308.4) grade ≥2 2558 (146.8) 7838 (163.7) grade ≥3 210 (12.1) 610 (12.7) serious aes 110 (6.3) 371 (7.8) fatal aesa 1 (0.1) 2 (<0.1) ae, adverse event; n, number of aes; n, number of patients; py, total patient-years of exposure through the end of the study; teae, treatment-emergent ae. athe 3 fatal aes were 1 sudden death (cause undetermined), 1 cardiac arrest (267 days on brodalumab; event occurred 7 days after last dose), and 1 accidental death (motor vehicle accident). microsoft word 5. 690 proof done.docx skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 31 research letters a survey based study on the sun safety knowledge of students attending public schools in san antonio, tx venkata anisha guda, bs,1 sandra osswald, md2 1ut health san antonio long school of medicine 2ut health san antonio department of dermatology 1 in 5 americans will develop skin cancer in their lifetime but 80% of skin cancer is preventable. according to the world health organization, the majority of sun exposure occurs before the age of 18.1 because children spend much of their time outdoors, teachers should ensure students have enough knowledge to protect themselves from the sun. children and adolescents are much more likely to listen to important health messages in a school environment, as they feel safe, comfortable, have peer support, and role models they see in teachers.2,3 by developing proper sun protection practices at a young age, students will be more likely to continue these practices into adulthood.2 after speaking with various educators and parents in the san antonio, tx community, it became apparent that insufficient information is provided to students and families regarding sun damage and protection. be sun safe is 1 in 5 americans will develop skin cancer in their lifetime but 80% of skin cancer is preventable. according to the world health organization, the majority of sun exposure occurs before the age of 18. because children spend much of their time outdoors, teachers should ensure students have enough knowledge to protect themselves from the sun. after speaking with various educators and parents in the san antonio, tx community, it became apparent that insufficient knowledge is provided to students and families regarding sun damage and protection. a 1 hour powerpoint presentation was created and given to 3rd grade and 5th grade classes at 10 public elementary schools in san antonio, tx. an 8-question pretest and posttest was also provided to the students. the 8-question test assessed how much the students had learned from the presentation, if they currently protect themselves from the sun, and whether they use sunscreen. 106 students in 3rd grade and 95 students in 5th grade took both preand posttests. both classes improved their score from the pre to the posttest. 3rd graders missed an average of 2.45 questions on the pretest and 2.12 questions on the posttest. 5th graders missed an average of 3.29 questions on the pretest and 1.21 questions on the posttest. additionally, only 37% of 3rd graders and 15% of 5th graders claimed that they always use sunscreen. from the results of the study, it is apparent that students improved their knowledge regarding sun damage and protection by listening to the presentation. therefore, it is imperative that children, parents, and teachers continue to be educated in san antonio, tx so that the next generation can protect themselves from the sun. abstract skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 32 an innovative curriculum that was developed to address this problem. a short powerpoint presentation as well as an educational handout were provided to children in san antonio regarding sun damage and protection. the powerpoint and handout focused on explaining the negative effects of uv damage, how sun exposure can lead to skin cancer, who is at risk for getting skin cancer, the optimal amount of time people should be out in the sun, how frequently sunscreen should be applied, and the spf value of sunscreen that should be purchased. the presentation and handout were evaluated by local educators in san antonio. a 1-hour powerpoint presentation was given to 3rd grade and 5th grade classes at 10 public elementary schools in san antonio, tx. an 8question pretest and posttest was also provided to the students. the 8-question test assessed how much the students had learned from the presentation, if they currently protect themselves from the sun, and whether they use sunscreen. the data collected was utilized to determine the effectiveness of the presentation and what needs to be done to help students, parents, and teachers increase their protection from the sun. 106 students in 3rd grade and 95 students in 5th grade took the preand posttest. both classes improved their score from the preto the posttest. 3rd graders missed an average of 2.454 questions on the pretest and 2.121 questions on the posttest. 5th graders missed an average of 3.290 questions on the pretest and 1.210 questions on the posttest (figure 1). additionally, only 37% of 3rd graders and 15% of 5th graders claimed that they always use sunscreen (figure 2). the most commonly missed question on the pretest was “who is at risk for getting skin cancer and the time of greatest sun exposure?”. the most commonly missed question on the posttest was “what is the mechanism by which sun damage leads to skin cancer?”. figure 1. figure 2. the study results clearly demonstrate that students improved their knowledge regarding sun damage and protection by listening to the presentation. it seems that the 5th graders were less knowledgeable regarding sun damage and protection compared to the 3rd graders. these class groups may need to be educated more. moreover, many of the 5th grade students do not protect themselves from the sun, according to the survey. there is also a limited number of students that always use sunscreen. therefore, it is imperative that children, parents, and teachers continue to be educated in san antonio, tx so that the next generation can properly protect themselves from the harmful effects of the excessive sun exposure. it would also be interesting to see how this data 0 20 40 60 always sometimes rarely never n um be r of s tu de nt s frequency of usage of sunscreen amongst students 3rd grade 5th grade skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 33 varies from state to state and how other age groups would perform on the pre and post test. i plan to follow up with these kids in the future to see whether their knowledge regarding sun protection has improved with time. conflict of interest disclosures: none funding: none corresponding author: venkata anisha guda, bs ut health san antonio long school of medicine email: gudav@livemail.uthscsa.edu references: 1. green ac, wallingford sc, mcbride p. childhood exposure to ultraviolet radiation and harmful skin effects: epidemiological evidence. prog biophys mol biol. 2011;107(3):349–355. doi:10.1016/j.pbiomolbio.2011.08.010 2. davis kj, cokkinides ve, weinstock ma, o’ connell mc, and wingo pa. summer sunburn and sun exposure among us youths aged 11 to 18: national prevalence and associated factors. pediatrics. 2002;110(1):27-35 3. hoel dg, berwick m, de gruijl fr, holick mf. the risks and benefits of sun exposure 2016. dermatoendocrinol. 2016;8(1):e1248325. published 2016 oct 19. doi:10.1080/19381980.2016.1248325 skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 802 brief article hidradenitis suppurativa: a cross-sectional study of content quality on tiktok ramneek k. dhami, bs1*, raquel m. wescott, bs1*, lingchen wang, ms2, whitney hovenic, md1,3 1 university of nevada, reno, school of medicine, reno, nv 2 school of public health, university of nevada, reno, reno, nv 3 skin cancer and dermatology institute, reno, nv *these authors contributed equally to this work tiktok is a social media platform with 1 billion monthly active users1 and is often used as an educational tool. creators share their experiences with or provide education regarding medical diagnoses, such as hidradenitis suppurativa (hs). with its growing popularity, evaluating the educational quality of tiktok videos is important. therefore, this study investigated the educational quality of tiktok videos for hs. abstract introduction: tiktok is a social media platform that is sometimes used to share medical information. creators share their experiences with or provide education regarding medical diagnoses. this study investigated the content quality of tiktok videos regarding hidradenitis suppurativa (hs). methods: on october 24, 2022, we searched #hidradenitissuppurativa on tiktok and filtered by most liked videos. two independent reviewers analyzed the videos, excluding those not in english, irrelevant to hs, and duplicates. videos were scored using the global quality scale (gqs), a one question scale (1-poor quality to 5-excellent quality), and the discern tool, a 15-question analysis (1-low quality to 5-high quality). results: one-hundred videos were included. mean gqs score was 2.49 [sd 0.87] and mean total discern score was 24.83 [sd 7.70], with substantial interrater reliability (cohen’s kappa 0.667). twenty-six videos (26%) were physician-created and 74 (74%) were non-physician-created. mean gqs and mean total discern scores for physician versus non-physician videos were 3.40 and 38.65, and 2.16 and 26.11, respectively. both mean gqs and mean total discern scores were greater for videos created by physicians versus non-physicians (p < 0.0001). conclusion: overall, there is a lack of information on treatment benefits, risks, and mechanisms of action. given the mean gqs and discern scores, the average video was of generally poor quality, creating potential for lack of knowledge and misinformation regarding hs. with the growing use of tiktok for educational purposes, improving content quality should be a priority to provide accurate information regarding medical conditions such as hs. introduction skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 803 on october 24, 2022, using the search term #hidradenitissuppurativa, we sorted by most liked videos and identified the top 147. two independent reviewers analyzed the videos, excluding those not in english, irrelevant to hs, and duplicates. thus, 100 videos were included. videos were scored using the global quality scale (gqs)2, a one-question score of quality ranging from 1 (poor quality) to 5 (excellent quality), and the discern tool3, a 15-question analysis ranging from a score of 1 (low quality) to 5 (high quality) for each, and categorized by score ranges, as previously reported in the literature.4 this protocol and outcome measures are consistent with a previous study on content quality of tiktok videos regarding hs5, with the addition of gqs score in this analysis. the top 100 videos had a combined total of 6,465,874 likes, with an average of 64,659 likes [sd 167486.44] per video. the mean gqs score was 2.49 [sd 0.87] and mean total discern score was 24.83 [sd 7.70], with substantial interrater reliability (cohen’s kappa 0.667). twenty-six videos (26%) were created by physicians and 74 (74%) were created by non-physicians. mean gqs and mean total discern scores for physiciancreated videos were 3.40 and 38.65, respectively. mean gqs and mean total discern scores for non-physician-created videos were 2.16 and 26.11, respectively (table 1). both mean gqs and mean total discern scores were greater for videos created by physicians versus non-physicians (p<0.0001) (figure 1). among discern scores, 0% of videos were “excellent” (63-75 points), 0% of videos were “good” (51-62.9 points), 17% (n = 17) were “average” (3950.9 points), 28% (n = 28) were “poor” (2838.9 points), and 55% (n = 55) were “very poor” (< 28 points). our results replicated those of the previous study5 regarding physician versus nonphysician discern scores. however, our results included an additional form of quality analysis, the gqs score, in which physician creators again had a higher mean score than non-physician creators. importantly, 82% of videos included in this study were posted after the search date of the previous paper.5 even among physician-created videos, there is a lack of information on treatment mechanisms of action, benefits, and risks. creators can improve video quality by including treatment information, sources of their content, and current research. limitations include the cross-sectional design of this study and the large difference in magnitude of videos created by physicians versus non-physicians, which should be acknowledged when considering the results. most videos did not include references or their publication dates, potentially affecting discern scores for question 5, as many scores were determined by the post date of the video. while gqs and discern scores have been validated tools for determining information quality, they generally assess written quality5, and a scale for rating video quality should be developed to accurately assess videos. with the growing use of tiktok for educational purposes, improving content quality of videos should become a priority to provide accurate information regarding medical conditions such as hs. conflict of interest disclosures: none funding: none methods results discussion skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 804 table 1. analysis of the 100 most-liked hidradenitis suppurativa videos on tiktok. creator type number of videos (n=100) mean number of likes mean gqs scores mean total discern scores physician 26 112,302 3.40 38.65 board-certified dermatologist 20 141,016 3.53 40.15 nondermatologist physician 6 16,589 3.0 33.67 non-physician 74 48,506 2.16 26.11 patient 68 25,190 2.15 26.02 esthetician/ beautician 3 604,967 2.33 27.67 other medical provider 2 6,563 2.50 26.50 other 1 5,063 2.00 27.00 gender male 25 114,554 2.92 34.54 female 75 48,027 2.34 27.65 video type personal anecdote 44 27,793 2.08 25.57 educational content 37 77,765 3.19 35.28 home remedies 10 12,857 2.10 25.30 treatment 5 37,274 2.50 32.30 other 3 682,733 1.33 23.67 advertisement/ product review 1 2,546 1.50 22.00 skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 805 figure 1. hidradenitis suppurativa global quality scale (gqs) and discern (q1-q15) score averages for physician versus non-physician creators. parentheses adjacent to the question number for discern scores indicate the content being scored by each question. gqs is a one question score using a scale of 1-5 (poor quality excellent quality) while discern is a 15-question scoring system, also using a scale of 1-5 (questions 1-15: 1 = no, 3 = partially, 5 = yes), indicating content quality. the difference between physician versus non-physician creators was statistically significant (p<0.0001). skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 806 corresponding author: raquel m. wescott 1664 n virginia st. reno, nv, 89557 email: rwescott@med.unr.edu references: 1. doyle b. tiktok statistics everything you need to know [sep 2021 update]. wallaroo media. published september 27, 2021. https://wallaroomedia.com/blog/socialmedia/tiktokstatistics/#:~:text=monthly%20active%20users% 20%e2%80%93%20tiktok%20officially 2. bernard a, langille m, hughes s, rose c, leddin d, veldhuyzen van zanten s. a systematic review of patient inflammatory bowel disease information resources on the world wide web. am j gastroenterol. 2007;102(9):20702077. doi:10.1111/j.1572-0241.2007.01325.x 3. charnock d, shepperd s, needham g, gann r. discern: an instrument for judging the quality of written consumer health information on treatment choices. j epidemiol community health. 1999;53(2):105-111. doi:10.1136/jech.53.2.105 4. weil ag, bojanowski mw, jamart j, gustin t, lévêque m. evaluation of the quality of information on the internet available to patients undergoing cervical spine surgery. world neurosurg. 2014;82(1-2):e31-e39. doi:10.1016/j.wneu.2012.11.003 5. rehman r, saad m, huq f, oska s, mehregan d, daveluy s. a cross-sectional analysis of popular hidradenitis suppurativa content on tiktok. jaad int. 2021;5:98-100. published 2021 oct 11. doi:10.1016/j.jdin.2021.09.004 association of patient-reported disease burden and treatment switching among patients with plaque psoriasis on nonbiologic systemic therapy sang hee park,1 yichen zhong,1 adam sima,2 vardhaman patel,1 joe zhuo,1 carla roberts-toler,2 brandon becker,1 sara hovland,1 bruce strober3,4 1bristol myers squibb, princeton, nj; 2corevitas, llc, waltham, ma; 3yale university, new haven, ct; 4central connecticut dermatology, cromwell, ct presented at the winter clinical dermatology conference hawaii®, january 13-18, 2023, kohala coast, hi, and winter clinical miamitm, february 17-20, 2023, miami, fl email for sang hee park, mph: sarah.park@bms.com this poster may not be reproduced without written permission from the authors. synopsis • psoriasis is a chronic, immune-mediated, inflammatory disease that affects up to 3.0% of the us population and can profoundly impair patients’ quality of life1,2 • how these impairments affect psoriasis treatment patterns warrants further investigation to help guide therapeutic algorithms • this cross-sectional, real-world study evaluated the association between patient-reported disease burden and switching from nonbiologic systemic to biologic therapy in biologic-naive patients with plaque psoriasis who enrolled in the corevitas psoriasis registry • odds of switching to biologic treatment were estimated with multivariable logistic regression models fitted for various patient-reported disease burden measures — models were adjusted for patient demographics, clinical characteristics, and disease severity • significantly higher adjusted odds of switching from nonbiologic systemic to biologic treatment were observed for patients with greater vs lesser burden for several health-related quality of life (hrqol) measures, irrespective of patients’ skin clearance • patient-reported hrqol burden, in addition to clinically observed disease severity, may drive the switch to biologic treatment among real-world patients with psoriasis objectives • to describe and compare patient-reported disease burden of psoriasis in biologic-naive patients who were using nonbiologic systemic therapy and switched to biologic treatment vs those who continued their initial systemic therapy with no changes • to compare the odds of switching to biologic treatment for different measures of patient-reported disease burden for patients who do and who do not have a low degree of skin involvement methods cross-sectional study design • inclusion criteria — enrolled in the corevitas psoriasis registry • a prospective, multicenter, noninterventional registry for patients with psoriasis under the care of a dermatologist, the registry includes 259 clinical sites throughout 46 states and provinces in the united states and canada — history of plaque psoriasis — ≥ 18 years of age — no previous use of biologic treatment — had used nonbiologic systemic therapy (ie, apremilast, acitretin, cyclosporine, or methotrexate) for ≥ 28 days and no more than 365 days prior to registry enrollment • the outcome measure was a switch to biologic treatment up to 45 days after registry enrollment — switching was defined as the introduction of a biologic therapy in addition to, or in place of, their current nonbiologic systemic therapy vs continuation of initial nonbiologic systemic treatment with no changes • biologic therapies included adalimumab, certolizumab, etanercept, infliximab, ustekinumab, guselkumab, risankizumab, tildrakizumab, secukinumab, ixekizumab, brodalumab, and bimekizumab — patients were excluded if they had switched from one nonbiologic systemic treatment to another • the study period extended from april 2015 to august 2022 — because of the timeline, the study did not include switching from deucravacitinib, an oral, allosteric, selective tyrosine kinase 2 (tyk2) inhibitor approved by the us food and drug administration for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy3 independent variables • at registry enrollment, patients completed self-reported measures of disease burden — dermatology life quality index (dlqi) • 10 items assessed dermatology-specific hrqol • total scores ranged from 0-30, with higher scores indicating poorer quality of life — visual analog scale (vas) ratings for itch, skin pain, and fatigue (each considered separate measures) • on a 100-mm horizontal line, patients rated their perceptions of each symptom’s severity over the past week, with 0 indicating absence of the symptom and 100 indicating the highest degree of symptom severity — euroqol 5-dimension 3-level (eq-5d-3l) questionnaire • a descriptive questionnaire with 5 dimensions (walking problems, self-care, usual activities, pain/discomfort, and anxiety/depression) • each dimension had 3 response levels of severity: no problems, moderate problems, extreme problems — work productivity and activity impairment questionnaire (wpai), activities impairment subscale • the activities impairment subscale corresponded to question 6 of the wpai (“to what degree has psoriasis affected your regular activities over the past 7 days?”) • scores out of 10 were multiplied by 100, with higher scores indicating greater impairment — patient global assessment vas (pga-vas) • on a 100-mm horizontal line, patients placed a mark representing how well they were doing with respect to the ways in which psoriasis affected them • scores of 0 indicated “very well” whereas scores of 100 indicated “very poorly” • thresholds for greater vs lesser burden for these measures, used in the published literature,4–8 are defined in table 1 table 1. greater vs lesser disease burden disease burden measure greater burden lesser burden dlqi4 > 5 ≤ 5 vas itch5 ≥ 30 < 30 vas skin pain6 ≥ 45 < 45 vas fatigue7 ≥ 50 < 50 eq-5d-3la moderate or extreme problems no problems wpai, activities impairment > 0 0 pga-vas8 ≥ 20 < 20 athe 5 subscale dimensions were walking problems, self-care, usual activities, pain/discomfort, and anxiety/depression. dlqi, dermatology life quality index; eq-5d-3l, euroqol 5-dimension 3-level questionnaire; pga-vas, patient global assessment, visual analog scale; vas, visual analog scale; wpai, work productivity and activity impairment questionnaire. analytic strategy • characteristics were descriptively compared between patients who did and who did not switch • multivariable logistic regression models were fitted separately for dlqi, vas itch, vas skin pain, vas fatigue, pga-vas, the activities impairment subscale of the wpai, and the 5 eq-5d-3l subscales — models were adjusted for age, sex, race, ethnicity, work status, body mass index, psoriasis duration, psoriatic arthritis status, number of prior nonbiologic systemics used prior to the study period, history of difficult-to-treat areas, and disease severity, as measured by body surface area (bsa) involvement, psoriasis area and severity index (pasi) score, and investigator’s global assessment (iga) score — adjusted odds of a switch with greater vs lesser burden were estimated for each measure/subscale • a secondary analysis stratified each model by whether patients had or did not have a low degree of skin involvement, defined as a pasi score ≤ 2 or > 2, respectively results descriptive comparisons of switchers and nonswitchers • the analytic sample included 848 patients, of whom 323 (38.1%) switched to biologic treatment • mean age at enrollment was 50.4 years, 54.1% of patients were female, and 78.8% of patients were white (table 2) • mean bsa involvement was 9.3% and mean pasi score was 5.0 (table 3) • mean age was lower in patients who switched, while bsa involvement, pasi score, and iga score were higher, with standardized differences > 0.3 (tables 2 and 3) — psoriatic arthritis was reported in 29.0% of patients who did not switch and 41.2% of patients who switched to biologic treatment (standardized difference: 0.26) table 2. demographic characteristics characteristic total n = 848 nonswitchers n = 525 switchers n = 323 standardized difference age, mean (sd), years 50.4 (15.6) 52.3 (15.3) 47.3 (15.6) 0.32 female, n (%) 459 (54.1) 288 (54.9) 171 (52.9) 0.04 race, n (%) white 668 (78.8) 411 (78.3) 257 (79.6) 0.04 black 29 (3.4) 19 (3.6) 10 (3.1) asian 89 (10.5) 55 (10.5) 34 (10.5) other 62 (7.3) 40 (7.6) 22 (6.8) hispanic ethnicity, n (%) 76 (9.0) 52 (9.9) 24 (7.4) 0.09 employed full-time, n (%) 450 (53.1) 263 (50.1) 187 (57.9) 0.16 body mass index, n (%) underweight/normal 188 (22.2) 111 (21.1) 77 (23.8) 0.16 overweight 258 (30.4) 174 (33.1) 84 (26.0) ≥ class 1 obesity 402 (47.4) 240 (45.7) 162 (50.2) any comorbidity history, n (%) 592/846 (70.0) 370/524 (70.6) 222/322 (68.9) 0.04 sd, standard deviation. table 3. psoriatic disease characteristics characteristic total n= 848 nonswitchers n = 525 switchers n = 323 standardized difference psoriasis duration, mean (sd), years 8.9 (12.0) 9.4 (12.2) 8.1 (11.6) 0.11 psoriatic arthritis, n (%) 285 (33.6) 152 (29.0) 133 (41.2) 0.26 body surface area involvement, % mean (sd) 9.3 (12.8) 6.1 (10.4) 14.6 (14.5) 0.68 mild (0–3), n (%) 262 (30.9) 235 (44.8) 27 (8.4) 1.03 moderate (3–10), n (%) 382 (45.0) 224 (42.7) 158 (48.9) severe (10–100), n (%) 204 (24.1) 66 (12.6) 138 (42.7) pasi score, mean (sd) 5.0 (5.9) 3.4 (5.2) 7.5 (6.1) 0.72 iga score, mean (sd) 2.4 (1.1) 1.9 (1.1) 3.1 (0.6) 1.27 unique nonbiologic systemics used prior to current systemic, n (%) 0 739 (87.1) 469 (89.3) 270 (83.6) 0.13 1 90 (10.6) 43 (8.2) 47 (14.6) ≥ 2 19 (2.2) 13 (2.5) 6 (1.9) duration of current therapy (< 90 days), n (%) 386 (45.5) 241 (45.9) 145 (44.9) 0.02 iga, investigator’s global assessment; pasi, psoriasis area and severity index; sd, standard deviation. odds of switching to biologic treatment, overall analysis • unadjusted odds of switching were significantly higher in patients who reported greater vs lesser burden as measured by the dlqi or by vas itch, skin pain, fatigue, or pga; in those who reported activities impairment on the wpai; and in those who reported moderate or extreme pain and discomfort, activities impairment, or anxiety/depression on the eq-5d-3l (p ≤ 0.003) — odds of switching were numerically higher among patients who reported moderate or extreme problems with walking or self-care on the eq-5d-3l • after adjusting for disease severity and baseline characteristics, greater disease burden was an independent predictor for treatment switching to biologics (figure 1) — patients with dlqi scores > 5 had 55% higher odds of switching than those with dlqi scores ≤ 5 (adjusted odds ratio [aor] = 1.55 [95% ci, 1.08–2.23], p = 0.017) — patients with greater burden for itch or skin pain had approximately twice the odds of switching compared with patients with less burden for these symptoms (itch aor = 2.14 [95% ci, 1.49–3.08], p < 0.001; skin pain aor = 2.18 [95% ci, 1.45–3.29], p < 0.001) — patients with greater burden for fatigue had 66% higher odds of switching than those with less burden for fatigue (aor = 1.66 [95% ci, 1.15–2.40], p = 0.007) — patients with activities impairment measured by the wpai had 2.5 times the odds of switching than those whose activities were not impaired on this measure (aor = 2.51 [95% ci, 1.72–3.65], p < 0.001) — patients who reported greater burden on the pga-vas had more than 3 times the odds of switching than those who reported lesser burden (aor = 3.09 [95% ci, 1.94–4.91], p < 0.001) • adjusted odds of switching to biologic treatment were numerically higher with greater burden measured by the eq-5d-3l, but these results’ wide confidence intervals merit interpretative caution figure 1. adjusted odds of switching to biologic treatment (n = 848) 0.1 1 pga-vas ≥ 20 wpai: activities impairment anxiety/depressiona pain and discomforta usual activitiesa self-care problemsa walking problemsa vas fatigue ≥ 50 vas skin pain ≥ 45 vas itch ≥ 30 dlqi > 5 aor, log scale (95% ci) g re at e r b u rd e n r e p o rt e d o n p r o m e as u re higher odds of switchinglower odds of switching 6 ameasured by the eq-5d-3l. aor, adjusted odds ratio; ci, confidence interval; dlqi, dermatology life quality index; eq-5d-3l, euroqol 5-dimension 3-level; pga-vas, patient global assessment, visual analog scale; pro, patient-reported outcome; vas, visual analog scale; wpai, work productivity and activity impairment questionnaire. adjusted odds of switching to biologic treatment, secondary analysis • of the 330 patients with pasi scores ≤ 2, 52 (15.8%) switched to biologic therapy • of the 518 patients with pasi scores > 2, 271 (52.3%) switched to biologic therapy • irrespective of stratification by pasi scores ≤ 2 or > 2, aors were significantly higher for patients with greater burden for vas itch, skin pain, or pga (p < 0.05) • figure 2 displays aors for switching for each measure in both subgroups — adjusted odds of switching were significantly higher for patients with pasi scores ≤ 2 who reported greater vs lesser burden for vas itch, skin pain, or pga, or impairment of usual activities on the eq-5d-3l (p < 0.05) — stratifying the sample by the skin clearance threshold reduced the sample size, resulting in more variable odds of switch estimates figure 2. adjusted odds of switching to biologic treatment by degree of skin involvement in (a) patients with pasi scores ≤ 2 (n = 330), and (b) patients with pasi scores > 2 (n = 518) 0.1 1 10 aor, log scale (95% ci) lower odds of switching a. b. higher odds of switching pga-vas ≥ 20 wpai: activities impairment anxiety/depressiona pain and discomforta usual activitiesa self-care problemsa walking problemsa vas fatigue ≥ 50 vas skin pain ≥ 45 vas itch ≥ 30 dlqi > 5 0.1 1 10 aor, log scale (95% ci) lower odds of switching higher odds of switching pga-vas ≥ 20 wpai: activities impairment anxiety/depressiona pain and discomforta usual activitiesa self-care problemsa walking problemsa vas fatigue ≥ 50 vas skin pain ≥ 45 vas itch ≥ 30 dlqi > 5 ameasured by the eq-5d-3l. aor, adjusted odds ratio; ci, confidence interval; dlqi, dermatology life quality index; eq-5d-3l, euroqol 5-dimension 3-level; pasi, psoriasis area and severity index; pga-vas, patient global assessment, visual analog scale; vas, visual analog scale; wpai, work productivity and activity impairment questionnaire. conclusions • the real-world evidence included in this study contains clinical data and patient-reported outcomes not available in claims databases; however, this study does not include longitudinal data • after adjusting for covariates that included disease severity measures, biologic-naive patients with psoriasis who reported greater hrqol burden had higher odds of switching to biologic therapy than those who reported lesser hrqol burden • the observed association of hrqol burden with a switch to biologic therapy was similar, irrespective of whether patients had a low degree of skin involvement (pasi scores ≤ 2) — even among patients with pasi scores ≤ 2, a switch to biologic therapy was observed for patients who reported greater hrqol burden • patient-reported hrqol burden, as well as clinically observed disease severity, may drive the switch to biologic treatment among patients with psoriasis references 1. armstrong aw, et al. jama dermatol. 2021;157:940–946. 2. liang se, et al. dermatol ther. 2019;32:e12771. 3. sotyktu [prescribing information]. princeton, nj: bristol myers squibb; 2022. 4. mrowietz u, et al. arch dermatol res. 2011;303:1–10. 5. reich a, et al. acta derm venereol. 2017;97:759–760. 6. jensen mp, et al. j pain. 2003;4:407–414. 7. skoie im, et al. br j dermatol. 2017;177:502–512. 8. lubrano e, et al. j rheumatol. 2015;42:2332–2338. acknowledgments • this study was sponsored by corevitas, llc. corevitas has been supported through contracted subscriptions in the last two years by abbvie, amgen, inc., arena, boehringer ingelheim, bristol myers squibb, celgene, chugai, eli lilly and company, genentech, gilead sciences, inc., glaxosmithkline, janssen pharmaceuticals, inc., leo pharma, novartis, ortho dermatologics, pfizer, inc., regeneron pharmaceuticals, inc., sanofi, sun pharmaceutical industries ltd., and ucb s.a. • medical writing and editorial assistance was provided by eleanor bush, ma, of peloton advantage, llc, an open health company, and funded by bristol myers squibb disclosures • shp, yz, vp, sh, jz, bb: employees of and may own stock options in bristol myers squibb • as, cr-t: employees of corevitas • bs: consultant (honoraria): abbvie, almirall, amgen, arcutis, arena, aristea, asana, boehringer ingelheim, bristol myers squibb, connect biopharma, dermavant, eli lilly, equillium, glaxosmithkline, immunic therapeutics, janssen, leo pharma, maruho, meiji seika pharma, mindera health, novartis, ortho dermatologics, pfizer, regeneron, sanofi genzyme, sun pharma, ucb, ventyxbio, and vtv therapeutics; speaker: abbvie, eli lilly, janssen, and sanofi genzyme; co-scientific director (consulting fee): corevitas' (corrona) psoriasis registry; investigator: abbvie, cara, corevitas' (corrona) psoriasis registry, dermavant, dermira, and novartis presented at the 2022 fall clinical dermatology conference; october 20 23, 2022; las vegas, nevada copies of this e-poster obtained through qr, ar and/or text key codes are for personal use only and may not be reproduced without written permission of the authors https://scientificpubs.congressposter.com/ p/w3jtgj6hk898hm9d impact of disease history on the efficacy of ritlecitinib (pf-06651600) in patients with alopecia areata: post hoc analysis of the allegro phase 2b/3 study brett king,1 wilma bergfeld,2 paweł brzewski,3 özge aşkin,4 thierry passeron,5,6 simran randhawa,7 ernest law,7 roger a. edwards,8 robert wolk,7 samuel h. zwillich,7 alexandre lejeune9 1yale university school of medicine, new haven, ct, usa; 2cleveland clinic, cleveland, oh, usa; 3department of dermatology, collegium medicum, jagiellonian university, krakow, poland; 4cerrahpaşa medical faculty, department of dermatology and venerology, istanbul university-cerrahpaşa, istanbul, turkey; 5université côte d’azur, chu nice, department of dermatology, nice, france; 6université côte d’azur, inserm, u1065, c3m, nice, france; 7pfizer inc, usa; 8health services consulting corporation, boxborough, ma, usa; 9pfizer inc, paris, france background • alopecia areata (aa) is an autoimmune disease with an underlying immuno-inflammatory pathogenesis and is characterized by non scarring hair loss ranging from small bald patches to complete loss of scalp, face, and/or body hair1 • ritlecitinib, an oral jak3/tec inhibitor, demonstrated efficacy and safety in patients aged ≥12 years with aa in the allegro phase 2b/3 study (nct03732807)2 • disease history, including disease duration and/or episode duration, has been associated with severity, prognosis, and treatment efficacy in aa3-5 objective • this post hoc analysis aimed to assess the impact of disease duration and duration of current aa episode on response to ritlecitinib • descriptive analyses were further conducted to analyze the contribution of current episode duration on response to ritlecitinib methods study design • the allegro phase 2b/3 trial was an international, randomized, double-blind, placebo-controlled, combined dose-ranging and pivotal phase 2b/3 study (figure 1) • patients received daily ritlecitinib (with or without a 200-mg loading dose in the first 4 weeks): 200/50, 200/30, 50, 30, or 10 mg (10 mg assessed for dose ranging only), or placebo for 24 weeks • during the 24-week extension, ritlecitinib groups continued on the 50-, 30-, or 10-mg maintenance doses, and patients initially assigned to placebo switched to ritlecitinib 200/50 or 50 mg daily key eligibility criteria • patients were ≥12 years of age with a diagnosis of aa and ≥50% scalp hair loss, including patients with alopecia totalis (at) and alopecia universalis (au), and a current aa episode duration of 6 months to 10 years figure 1. study design bl, baseline; qd, once daily; rit, ritlecitinib. outcomes and statistical analysis • in this post hoc analysis, multivariable logistic regression with 2 different variable selection methods was used to evaluate the effect of ritlecitinib (vs placebo), baseline disease duration, and current aa episode duration (both <1 year vs ≥1 year) on response based on severity of alopecia tool (salt) score ≤20 (≤20% scalp without hair) at week 24, while controlling for other covariates covariates listed below were included in the models to evaluate the independent effect of disease and episode duration: • age (continuous) • sex (male vs female) • race (white vs other; asian vs other) • body mass index (bmi; continuous) • current episode duration (<1 year vs ≥1 year) • disease duration (<1 year vs ≥1 year) • extent of aa (at/au vs non-at/au) • prior pharmacological treatment for aa (yes or no) • eyelash hair loss at baseline (continuous) • eyebrow hair loss at baseline (continuous) • active shedding (yes vs no) • treatment arm (ritlecitinib vs placebo; excluding 10-mg group) • the 2 multivariable logistic regression models included in this analysis were: all variables model: considered all covariates listed above to adjust for the variables of interest stepwise model: a stepwise approach was taken for additional sensitivity analysis; nonsignificant covariates were excluded from this model to increase precision for the independent variables of interest odds ratios (ors) and 95% cis were reported for both logistic regression models • an additional descriptive subgroup analysis assessed the proportions of patients with response based on salt score ≤20 at week 48 by episode duration <1 or ≥1 year for active ritlecitinib treatment arms (200/50, 200/30, 50, and 30 mg) • irrespective of the modeling approach taken, all active ritlecitinib regimens were significantly positively associated with salt score ≤20 response vs placebo at week 24 (figures 2 and 3) • while disease duration was not significantly associated with salt score ≤20 response at week 24 (figure 2), shorter episode duration (<1 year) was significantly positively associated with salt score ≤20 response, irrespective of the model used (figure 3) figure 2. odds ratios for salt score ≤20 response at week 24 based on (a) ritlecitinib dose vs placebo and (b) disease and episode duration (<1 vs ≥1 year) in the all variables model* aa, alopecia areata; at, alopecia totalis; au, alopecia universalis; or, odds ratio; salt, severity of alopecia tool. *blue markers indicate independent covariates of interest that were significant in the all variables model. covariates that were not significant are shown in grey. other significant covariates (not shown) included sex (male vs female) and extent of aa (at/au vs non-at/au). results • at baseline, mean (range) duration of disease since initial diagnosis was 10.06 (0.04-60.11) years and duration of current aa episode was 3.35 (0.02-9.97) years; most patients had disease and episode duration ≥1 year (table 1) table 1. baseline characteristics ritlecitinib qd 200/50 mg (n=132) 200/30 mg (n=130) 50 mg (n=130) 30 mg (n=132) 10 mg (n=63) placebo* (n=131) age mean (sd), years 34.5 (15.0) 33.7 (13.8) 32.4 (13.4) 33.7 (14.8) 34.3 (13.9) 34.0 (15.0) 12-17 years, n (%) 20 (15.2) 19 (14.6) 18 (13.8) 20 (15.2) 9 (14.3) 19 (14.5) ≥18 years, n (%) 112 (84.8) 111 (85.4) 112 (86.2) 112 (84.8) 54 (85.7) 112 (85.5) female, n (%) 81 (61.4) 85 (65.4) 71 (54.6) 80 (60.6) 43 (68.3) 86 (65.6) race, n (%) white 92 (69.7) 90 (69.2) 79 (60.8) 91 (68.9) 42 (66.7) 94 (71.8) bmi, mean (sd), kg/m2 25.2 (4.9) 25.2 (5.3) 24.7 (5.0) 24.9 (4.7) 24.5 (5.6) 25.0 (6.2) at/au, n (%) 60 (45.5) 60 (46.2) 60 (46.2) 61 (46.2) 29 (46.0) 60 (45.8) baseline salt score, mean (sd) all patients 90.3 (15.1) 90.5 (14.3) 90.3 (14.7) 90.0 (15.1) 88.3 (16.9) 93.0 (11.5) non-at/au† 82.2 (16.5) 82.4 (15.4) 82.0 (15.9) 81.5 (16.27) 78.3 (17.6) 87.0 (12.9) duration of current aa episode mean (sd), years 3.4 (2.93) 3.4 (2.89) 3.2 (2.67) 3.6 (2.82) 3.3 (2.65) 3.2 (2.65) <1 year, n (%) 32 (24.4) 28 (21.7) 30 (23.1) 26 (19.7) 16 (25.8) 31 (23.7) ≥1 year, n (%) 99 (75.6) 101 (78.3) 100 (76.9) 106 (80.3) 46 (74.2) 100 (76.3) duration of disease since initial diagnosis mean (sd), years 9.9 (10.8) 11.6 (11.7) 8.7 (8.7) 8.8 (8.9) 10.8 (10.7) 11.0 (11.8) <1 year, n (%) 10 (7.6) 10 (7.8) 14 (10.8) 10 (7.6) 5 (8.1) 14 (10.7) ≥1 year, n (%) 121 (91.2) 119 (92.2) 116 (89.2) 122 (92.4) 57 (91.9) 117 (89.3) any prior pharmacological treatment for aa, n (%) 91 (68.9) 78 (60.0) 100 (76.9) 91 (68.9) 44 (69.8) 95 (72.5) aa, alopecia areata; at, alopecia totalis; au, alopecia universalis; bmi, body mass index; qd, once daily; salt, severity of alopecia tool. *placebo for 24 weeks and then switched to ritlecitinib 200/50 mg or 50 mg. †participants in the at/au category had a salt score of 100 (complete scalp hair loss) at baseline. 0 200 250 30010050 150 0 3 41 2 43.79 (12.26-281.31) 27.02 (7.45-174.66) 25.73 (7.13-165.78) 15.76 (4.20-103.23) or (95% ci) 0.49 (0.27-0.89) 1.35 (0.54-3.59) or (95% ci) ritlecitinib 200/50 mg (vs placebo) ritlecitinib 200/30 mg (vs placebo) ritlecitinib 50 mg (vs placebo) ritlecitinib 30 mg (vs placebo) episode duration ≥1 year (vs <1 year) disease duration ≥1 year (vs <1 year) variable variable a. treatment arm b. disease and episode duration figure 3. odds ratios for salt score ≤20 response at week 24 based on (a) ritlecitinib dose vs placebo and (b) disease and episode duration (<1 vs ≥1 year) in the stepwise model* aa, alopecia areata; at, alopecia totalis; au, alopecia universalis; or, odds ratio; salt, severity of alopecia tool. *blue markers indicate independent covariates of interest that were significant in the stepwise model. other significant covariates (not shown) included sex (male vs female), extent of aa (at/au vs non-at/au), and eyebrow hair loss at baseline. disease duration (<1 year vs ≥1 year) was excluded from the stepwise model. • while across active ritlecitinib doses (200/50, 200/30, 50, or 30 mg), a substantial proportion of patients with episode duration ≥1 year were salt score ≤20 responders at week 48, the proportion of patients with salt score ≤20 response was numerically higher in those with episode duration <1 year (figure 4) figure 4. proportion of patients with salt score ≤20 response at week 48 by current aa episode duration <1 or ≥1 year aa, alopecia areata; salt, severity of alopecia tool. limitations • one-year thresholds for disease and episode duration were selected based on clinical relevance but were not used to stratify patients at enrollment; results may differ based on different thresholds for disease and episode duration treatment conclusions • treatment with ritlecitinib results in an increased likelihood of treatment response regardless of disease duration or duration of aa episode • however, episode duration was independently associated with a reduced likelihood of salt score ≤20 response, suggesting that while ritlecitinib is efficacious in aa regardless of disease duration, there is a potential benefit of initiating ritlecitinib therapy early in the course of an aa episode • further studies are needed to better understand the impact of disease history on clinical efficacy of aa treatments rit 200 mg qd rit 200 mg qd rit 50 mg qd rit 30 mg qd rit 10 mg qd placebo placebo rit 50 mg qd rit 30 mg qd rit 50 mg qd rit 30 mg qd rit 10 mg qd placebo placebo rit 50 mg qd rit 30 mg qd rit 50 mg qd rit 30 mg qd rit 10 mg qd rit 200/50 mg qd rit 50 mg qd placebo-controlled (24 weeks) study week extension (24 weeks) maintenance (20 weeks) loading (4 weeks) bl 2 4 8 12 18 26 28 34 40 4824 s cr ee ni ng r an do m iz at io n screening and randomization (35 days) n=132 n=66 n=65 n=63 n=130 n=132 n=130 0 200 250 30010050 150 0 3 41 2 44.99 (12.61-288.92) 27.39 (7.55-177.04) 26.03 (7.25-167.42) 16.04 (4.27-105.06) or (95% ci) 0.53 (0.31-0.89) or (95% ci) ritlecitinib 200/50 mg (vs placebo) ritlecitinib 200/30 mg (vs placebo) ritlecitinib 50 mg (vs placebo) ritlecitinib 30 mg (vs placebo) episode duration ≥1 year (vs <1 year) variable variable a. treatment arm b. episode duration ritlecitinib 200/50 mg ritlecitinib 200/30 mg ritlecitinib 50 mg ritlecitinib 30 mg 0 n: 32 59.4% 32.3% 35.7% 31.7% 50.0% 39.0% 42.3% 23.6% 99 28 101 30 100 26 106 10 20 30 40 50 60 70 80 p ro po rt io n of p at ie nt s w ith s a lt ≤ 20 at w ee k 48 , % <1 year ≥1 year episode duration references 1. islam n, et al. autoimmun rev. 2015;14:81-89. 2. king b, et al. poster presented at: 30th annual eadv meeting; september 29-october 2, 2021. 3. liu ly, et al. jaad. 2017;76:22-28. 4. king ba, et al. jaad. 2022;86:359-364. 5. meah n, et al. jaad. 2021;84:1594-1601. disclosures this study was sponsored by pfizer, inc. bk has received honoraria and/or consultation fees from abbvie, aclaris therapeutics, altrubio, almirall, arena pharmaceuticals, bioniz therapeutics, bristol myers squibb, concert pharmaceuticals, dermavant sciences, eli lilly, incyte, leo pharma, otsuka/visterra, pfizer, regeneron, sanofi genzyme, twi biotechnology, and viela bio and speakers bureau fees from pfizer inc. wb declares no conflicts of interests. pb has received honoraria and/or consultation fees from abbvie, concert pharmaceuticals, eli lilly, leo pharma, pfizer, sanofi genzyme, samsung, janssen, and novartis. ö.a. declares no conflicts of interests. tp has received honoraria and/or consultation fees from abbvie, almirall, amgen, bristol myers squibb, celgene, eli lilly, galderma, gsk, incyte, janssen, leo pharma, msd, novartis, pfizer, sanofi genzyme, sun pharma, and ucb pharma. rae is an employee of health services consulting corporation and received consultancy fees from pfizer in connection with this study. s.r., e.l., r.w., s.h.z., and a.l. are employees of pfizer and hold stock or stock options in pfizer. third-party medical writing assistance, provided by health interactions, inc, was funded by pfizer inc. skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 745 compelling comments hypertrichosis: the werewolf syndrome without a wolf pack kripa raj ahuja ms1 1eastern virginia medical school, norfolk, va hypertrichosis is defined as excess hair growth on the body that typically spares the palms and soles.1 while less than 50 cases are reported in the literature, it is important to recognize the magnitude of impact this disorder creates.1 sometimes colloquially known as “werewolf syndrome,” patients with hypertrichosis have been recorded since the middle age and the renaissance.2 historically, these patients were often exhibited in circuses for their peculiarity.2 unfortunately, the stigma against excess hair continues into the modern age.3 patients with hypertrichosis not only face social isolation and bullying but face numerous difficulties finding a job as well as finding a spouse.3 women face a higher burden, as it is less socially acceptable for women to have excess hair.3 patients with hypertrichosis continue to work in circuses, often before they can even walk.3 many women with hypertrichosis are single mothers due to partner abandonment.3 with no support, they have no choice but to be exhibited as a sideshow attraction and subject their child to the same fate.3 while there is no permanent cure for hypertrichosis2, the lack of an advocacy group, patient support network, or formal organization presents even greater hardships to patients with this disease.3 in a disorder characterized by an extremely high social stigma, a social network with others facing the same difficulties may make a world of difference. as one patient with hypertrichosis commented about wolves living in a zoo: "both of our faces are covered in hair, and we both live trapped them in the zoo and me in this body," he says. "at least the wolves treat me the same as they treat other humans.”3 figure 1. historical depiction of hypertrichosis. conflict of interest disclosures: none funding: none corresponding author: kripa ahuja, ms eastern virginia medical school phone: (407) 417-1983 email: ahujak@evms.edu skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 746 references: 1. de raeve l, keymolen k. congenital hypertrichosis lanuginosa in a father and son. arch dermatol. 2011;147(6):746. doi:10.1001/archdermatol.2011.137 2. pavone p, praticò ad, falsaperla r, et al. congenital generalized hypertrichosis: the skin as a clue to complex malformation syndromes. ital j pediatr. 2015;41:55. doi:10.1186/s13052-015-0161-3 3. the struggles of the world’s hairiest family. bbc news. https://www.bbc.com/news/magazine33978116. published august 31, 2015. accessed december 17, 2022. deucravacitinib in plaque psoriasis: 2-year laboratory results from the phase 3 poetyk pso program neil j korman,1 thierry passeron,2 kenneth b gordon,3 yukari okubo,4 jerry bagel,5 howard sofen,6 richard b warren,7 neal bhatia,8 lynda spelman,9 kevin winthrop,10 lauren hippeli,11 renata m kisa,11 subhashis banerjee,11 diamant thaçi12 1case western reserve university, university hospitals of cleveland, cleveland, oh, usa; 2côte d’azur university, university hospital of nice, nice, france; 3medical college of wisconsin, milwaukee, wi, usa; 4tokyo medical university, tokyo, japan; 5psoriasis treatment center of new jersey, east windsor, nj, usa; 6ucla school of medicine, los angeles, ca, usa; 7dermatology centre, salford royal nhs foundation trust, nihr manchester biomedical research centre, the university of manchester, manchester, uk; 8therapeutics clinical research, san diego, ca, usa; 9veracity clinical research, brisbane, qld, australia; 10oregon health & science university, portland, or, usa; 11bristol myers squibb, princeton, nj, usa; 12university of lübeck, lübeck, germany presented at the 2022 fall clinical dermatology conference; october 20—23, 2022; las vegas, nv this is an encore of the 2022 31st eadv congress poster this poster may not be reproduced without written permission from the authors.email for neil j korman, md, phd: neil.korman@uhhospitals.org scientific content on demand to request a copy of this poster: scan qr code via a barcode reader application qr codes are valid for 30 days after congress presentation date synopsis • tyrosine kinase 2 (tyk2) is an intracellular enzyme that mediates signaling of cytokines (interleukin-23 and type i interferons) involved in psoriasis pathogenesis1 • deucravacitinib, an oral, selective, allosteric tyk2 inhibitor, is approved by the us food and drug administration for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy2 • deucravacitinib has a unique mechanism of action, the first in a new class of small molecules1 (figure 1) • the selectivity of deucravacitinib facilitates a more targeted therapeutic approach that avoids signature laboratory changes seen with the janus kinase (jak) 1/2/3 inhibitors — in phase 2 and phase 3 trials (poetyk pso-1 and pso-2) in plaque psoriasis, deucravacitinib treatment did not result in neutropenia, elevated liver enzyme and serum creatinine levels, and dyslipidemia — adverse events that have been associated with jak 1/2/3 inhibitors3-7 • deucravacitinib demonstrated a robust efficacy profile, including superiority to placebo and apremilast and durability and maintenance of response, in 2 multinational phase 3 trials in patients with moderate to severe plaque psoriasis5,6,8 • patients who completed the poetyk pso-1 and pso-2 trials could enroll in the ongoing poetyk long-term extension (lte) trial objectives • to determine whether there were any clinically relevant changes in blood laboratory parameters with up to 2 years of deucravacitinib treatment in the poetyk pso-1, pso-2, and lte trials • to evaluate whether deucravacitinib treatment elicits changes in the blood that are known to occur with jak 1/2/3 inhibitors methods study designs • poetyk pso-1 (nct03624127) and pso-2 (nct03611751) were 52-week, multinational, phase 3, double-blind trials that randomized patients with moderate to severe plaque psoriasis 2:1:1 to deucravacitinib 6 mg once daily, placebo, or apremilast 30 mg twice daily (figure 2) • at week 52, eligible patients were able to enroll in the poetyk lte trial (nct04036435) and receive open-label deucravacitinib 6 mg once daily for up to 2 years figure 2. poetyk pso-1, pso-2, and lte study designs 100 poetyk pso-1 and pso-2 deucravacitinib 6 mg qdplacebo (n = 166) deucravacitinib 6 mg qd apremilast 30 mg bid titrate*p o e t y k p so -1 1 :2 :1 r an d o m iz at io n deucravacitinib 6 mg qd (n = 332) apremilast 30 mg bida (n = 168) deucravacitinib 6 mg qdplacebo (n = 255) deucravacitinib 6 mg qd (n = 511) deucravacitinib 6 mg qd<pasi 75 deucravacitinib 6 mg qd<pasi 75 deucravacitinib 6 mg qd apremilast 30 mg bida (n = 254) p o e t y k p so -2 1 :2 :1 r an d o m iz at io n cumulative 16 24 520 1 :1 deucravacitinib 6 mg qdplacebo deucravacitinib 6 mg qdplacebo primary endpoint b li n d e d s w it c h t o o p e n -l a b e l d e u c r a v a c it in ib open-label deucravacitinib 6 mg qd (n = 1221) poetyk lte 856 60 68 76 88 112 124 1364 8 12 20 28 32 36 40 44 48 480 964 8 16 24 36 60 72 84 ≥pasi 75 ≥pasi 75 <pasi 50 ≥pasi 50 safety assessed for all available data (currently 2 years)b aapremilast was titrated from 10 mg qd to 30 mg bid over the first 5 days of dosing. bdata reported through the cutoff date of october 1, 2021. bid, twice daily; lte, long-term extension; pasi 50, ≥50% reduction from baseline in psoriasis area and severity index; pasi 75, ≥75% reduction from baseline in pasi; qd, once daily. laboratory assessments • pooled poetyk pso-1 + pso-2 data over weeks 0—52 and pooled poetyk pso-1 + pso-2 + lte data over weeks 0—100 are presented • changes in laboratory parameters that are known to be affected by jak 1/2/3 inhibitors3 were evaluated in blood over time — hematologic parameters: lymphocytes, neutrophils, platelets, and hemoglobin — lipid parameter: total cholesterol — chemistry parameters: creatinine, creatine phosphokinase (cpk), and alanine aminotransferase (alt) • incidences of grade ≥3 laboratory abnormalities (common terminology criteria for adverse events [ctcae] version 5.0) and treatment discontinuations due to laboratory abnormalities were also evaluated through week 100 results patient population • this analysis included 1519 patients who received ≥1 dose of deucravacitinib in poetyk pso-1, pso-2, and/or the lte through the data cutoff date of october 1, 2021 — total deucravacitinib exposure was 2482.0 person-years (py) • in total, 1179 (77.6%) and 584 (38.4%) patients had ≥52 weeks and ≥104 weeks, respectively, of continuous deucravacitinib exposure at the data cutoff date — median duration of exposure was 682.0 days (97 weeks) • baseline patient demographics and disease characteristics are presented in table 1 laboratory assessments • no clinically meaningful changes were observed over weeks 0—100 in any of the evaluated laboratory parameters in the pooled poetyk pso-1/pso-2/lte population (figure 3) — laboratory parameters remained within normal ranges for most patients throughout this period • grade ≥3 laboratory abnormalities were rare (table 2) — frequencies of individual events were comparable across groups over the first 52 weeks (poetyk pso-1 and pso-2), and no increases were seen with deucravacitinib treatment through week 100 in the poetyk lte — grade ≥3 cpk elevations occurred rarely, were mostly transient, and were observed at a similar incidence in each treatment group over the first 52 weeks; almost all were related to recent physical exertion and none was serious • discontinuations due to laboratory abnormalities were low and balanced across treatment groups over the first 52 weeks and were also low through week 100 in the poetyk lte (table 3) — alt elevations in deucravacitinib-treated patients (table 2) were predominantly transient, and none was serious or resulted in treatment discontinuation figure 3. changes in hematologic, lipid, and chemistry parameters over 2 years in patients receiving deucravacitinib in poetyk pso-1 + pso-2 + lte 0 0 1 2 3 4 m e an ± s d , 1 0 9 /l 5 lymphocytes 4 8 12 20 28 32 44 48 56 64 68 76 84 88 92 100 n= 775 1031 1031 992 1139 0 0 2 4 6 m e an ± s d , 1 0 9 /l 8 neutrophils 4 8 12 20 28 32 44 48 56 64 68 76 84 88 92 100 n= 775 1031 1031 992 1139 0 100 200 300 m e an ± s d , 1 0 9 /l platelets 4 8 12 20 28 32 44 48 56 64 68 76 84 88 92 100 n= 784 747 1030 1132 1133 1132 0 12 13 m e an ± s d , g/ d l hemoglobin 4 8 12 20 28 32 44 48 56 64 68 76 84 88 92 100 n= 747 999 0 100 200 m e an ± s d , m g/ d l 300 total cholesterol 8 32 48 56 64 88 100 n= 755 0 m e an ± s d , m g/ d l creatinine 4 8 12 20 28 32 44 48 56 64 68 76 84 88 92 100 n= 765 758 992 0 0 m e an ± s d , u /l 1000 cpk 4 8 12 20 28 32 44 48 56 64 68 76 84 88 92 100 n= 764 757 1112 0 0 m e an ± s d , u /l alt 4 8 12 20 28 32 44 48 56 64 68 76 84 88 92 100 n= 764 757 1013 1112 20 alt, alanine aminotransferase; cpk, creatine phosphokinase; lln, lower limit of normal; lte, long-term extension; uln, upper limit of normal. table 2. ctcae grades 3 and 4 abnormalities in laboratory parameters over 1 and 2 years at 1 year (poetyk pso-1 + pso-2, weeks 0—52) at 2 years (poetyk pso-1 + pso-2 + lte, weeks 0—100) placebo (n = 666) deucravacitinib (n = 1364) apremilast (n = 422) deucravacitinib (n = 1519) parameter grade baseline n (%) week 52 n (%) baseline n (%) week 52 n (%) baseline n (%) week 52 n (%) baseline n (%) week 100 n (%) lymphocyte count decreased 3 0 1 (0.2)a 0 2 (0.1)b 0 1 (0.2)c 0 2 (0.1)d 4 0 0 0 0 0 0 0 0 neutrophil count decreased 3 0 1 (0.2)a 1 (0.1)b 4 (0.3)b 0 0 1 (0.1)d 5 (0.3)d 4 0 1 (0.2)a 0 0 0 1 (0.2)c 0 1 (0.1)d platelet count decreased 3 0 1 (0.2)e 0 0 0 0 0 0 4 0 0 0 0 0 0 0 0 anemia 3 0 0 0 0 0 1 (0.2)c 0 1 (0.1)d 4 0 0 0 0 0 0 0 0 high cholesterol 3 0 0 0 1 (0.1)f 0 0 0 1 (0.1)g 4 0 0 0 0 0 0 0 0 creatinine increased 3 0 0 0 0 0 0 0 0 4 0 0 0 0 0 0 0 0 cpk increased 3 1 (0.2)a 4 (0.6)a 3 (0.2)b 19 (1.4)b 1 (0.2)h 7 (1.7)h 3 (0.2)i 25 (1.7)i 4 0 3 (0.5)a 0 13 (1.0)b 0 1 (0.2)h 0 26 (1.7)i alt increased 3 2 (0.3)a 0 1 (0.1)b 4 (0.3)b 0 0 1 (0.1)i 10 (0.7)i 4 0 0 0 0 0 0 0 0 an = 658. bn = 1351. cn = 418. dn = 1503. en = 657. fn = 1317. gn = 1454. hn = 419. in = 1504. alt, alanine aminotransferase; cpk, creatine phosphokinase; ctcae, common terminology criteria for adverse events; lte, long-term extension. table 3. laboratory abnormality adverse events leading to treatment discontinuation over 1 and 2 years at 1 year (poetyk pso-1 + pso-2, weeks 0—52) at 2 years (poetyk pso-1 + pso-2 + lte, weeks 0—100) placebo (n = 666) total exposure = 240.9 py deucravacitinib (n = 1364) total exposure = 969.0 py apremilast (n = 422) total exposure = 221.1 py deucravacitinib (n = 1519) total exposure = 2482.0 py parameter n (%) eair/100 py n (%) eair/100 pya n (%) eair/100 pya n (%) eair/100 pya lymphopenia 0 0 1 (0.1) 0.1 0 0 1 (0.1) 0.0 blood cpk increased 0 0 2 (0.1) 0.2 1 (0.2) 0.4 3 (0.2) 0.1 hepatic function abnormal 1 (0.2)b 0.4 1 (0.1)c 0.1 0 0 1 (0.1) 0.0 ast increased 0 0 0 0 1 (0.2) 0.4 0 0 aincidences are expressed as eairs per 100 py to account for variable exposure due to treatment switches at weeks 16 and 24. bpatient who received placebo during weeks 0—16 had alt >3x uln on days 1 and 8; total bilirubin levels remained in the normal range. the patient discontinued placebo and alt levels improved. cpatient who received deucravacitinib during weeks 0—16 had alt and ast elevations ≥3x uln and bilirubin elevation >2x uln on day 58. deucravacitinib treatment was discontinued and alt, ast, and bilirubin levels improved. alt, alanine aminotransferase; ast, aspartate aminotransferase; cpk, creatine phosphokinase; eair, exposure-adjusted incidence rate; lte, long-term extension; py, person-years; uln, upper limit of normal. conclusions • in the large, phase 3 poetyk pso-1, pso-2, and lte trials in patients with plaque psoriasis, no trends or clinically meaningful changes in multiple hematologic, lipid, and chemistry parameters were observed in 1519 patients with 2482.0 py of deucravacitinib exposure — signature laboratory changes associated with jak 1/2/3 inhibitors were not observed over 2 years of deucravacitinib exposure • ctcae grade ≥3 laboratory abnormalities and treatment discontinuations due to laboratory abnormalities in deucravacitinibtreated patients were rare, and were comparable to incidence rates observed with placebo and apremilast over the first 52 weeks • deucravacitinib, a once-daily oral drug, has the potential to become a treatment of choice and new standard of care for patients who require systemic therapy for their moderate to severe plaque psoriasis references 1. burke jr, et al. sci transl med. 2019;11:eaaw1736. 2. sotyktutm (deucravacitinib) [package insert]. princeton, nj: bristol-myers squibb company; september 2022. 3. papp k, et al. n engl j med. 2018;379:1313-1321. 4. winthrop kl. nat rev rheumatol. 2017;13:234-243. 5. armstrong a, et al. j am acad dermatol. 2022;s0190-9622(22)02256-3. doi: 10.1016/j.jaad.2022.07.002. online ahead of print. 6. strober b, et al. j am acad dermatol. 2022;s0190-9622(22)02643-3. doi: 10.1016/j.jaad.2022.08.061. online ahead of print. 7. thaçi d, et al. presented at the european academy of dermatology and venereology (eadv) 30th congress; september 29—october 2, 2021. 8. warren rb, et al. presented at the european academy of dermatology and venereology (eadv) spring symposium; 12—14 may 2022; ljubljana, slovenia. 9. wrobleski st, et al. j med chem. 2019;62:8973-8995. acknowledgments • this study was sponsored by bristol myers squibb • writing and editorial assistance was provided by liz rockstein, phd, of peloton advantage, llc, an open health company, parsippany, nj, usa, funded by bristol myers squibb disclosures • njk: advisory board, consulting fees: abbvie, boehringer ingelheim, bristol myers squibb, celgene, eli lilly, janssen, leo pharma, novartis, principia, regeneron, sanofi genzyme, sun pharma, and ucb; grant support/principal investigator: abbvie, amgen, argenx, bristol myers squibb, celgene, chemocentryx, eli lilly, galderma, kyowa hakko kirin, leo pharma, menlo, principia, prothena, rhizen, syntimmune, trevi, and xbiotech; speaker: abbvie, eli lilly, janssen, novartis, regeneron, and sanofi genzyme • tp: advisory board and consulting fees: abbvie, almirall, amgen, boehringer ingelheim, bristol myers squibb, celgene, eli lilly, galderma, incyte, janssen, leo pharma, novartis, pfizer, sanofi genzyme, sun pharma, and ucb • kbg: grant support and consulting fees: abbvie, boehringer ingelheim, bristol myers squibb, celgene, eli lilly, janssen, novartis, and ucb; consulting fees: almirall, amgen, dermira, leo pharma, pfizer, and sun pharma • yo: research grants: eisai, maruho, shiseido, and torii; current consulting/advisory board agreements: abbvie, amgen, boehringer ingelheim, bristol myers squibb, eli lilly, janssen, and sun pharma; speakers bureau: abbvie, amgen, boehringer ingelheim, bristol myers squibb, celgene, eisai, eli lilly, janssen pharma, jimro, kyowa kirin, leo pharma, maruho, novartis, pfizer, sanofi, sun pharma, taiho, tanabe-mitsubishi, torii, and ucb; clinical trials: abbvie, amgen, boehringer ingelheim, bristol myers squibb, celgene, eli lilly, janssen, leo pharma, maruho, pfizer, sun pharma, and ucb • jb: research funds payable to the psoriasis treatment centre of new jersey: abbvie, amgen, arcutis, boehringer ingelheim, bristol myers squibb, celgene, corevitas’ (corrona) psoriasis registry, dermavant, dermira/ucb, eli lilly, glenmark, janssen biotech, kadmon, leo pharma, lycera, menlo therapeutics, novartis, pfizer, regeneron, sun pharma, taro, and valeant; consultant: abbvie, amgen, celgene, eli lilly, janssen biotech, novartis, sun pharma, and valeant; speaker: abbvie, celgene, eli lilly, janssen biotech, and novartis • hs: clinical investigator: abbvie, amgen, boehringer ingelheim, bristol myers squibb, eli lilly, janssen, leo pharma, novartis, and sun pharma • rbw: research grants: abbvie, almirall, amgen, celgene, eli lilly, janssen, leo pharma, novartis, pfizer, and ucb; consulting fees: abbvie, almirall, amgen, biogen, boehringer ingelheim, celgene, dice, eli lilly, janssen, leo pharma, novartis, pfizer, sanofi, ucb, and union • nb: advisor and consultant investigator: abbvie, almirall, arcutis, arena, boehringer ingelheim, bristol myers squibb, dermavant, incyte, isdin, johnson & johnson, leo pharma, lilly, ortho, pfizer, regeneron, sanofi, stemline, and sun pharma; investigator: arcutis, biofrontera, boehringer ingelheim, bristol myers squibb, dermavant, galderma, leo pharma, lilly, and ortho • ls: consultant, paid investigator, and/or speaker: abbvie, amgen, anacor, ascend, astellas, astrazeneca, blaze bioscience, bristol myers squibb, boehringer ingelheim, botanix, celgene, dermira, eli lilly, galderma, genentech, glaxosmithkline, hexima, janssen, leo pharma, mayne, medimmune, merck, merck-serono, novartis, otsuka, pfizer, phosphagenics, photon md, regeneron, roche, samumed, sanofi genzyme, shr, sun pharma anz, trius, ucb, and zai lab • kw: consulting: abbvie, astrazeneca, bristol myers squibb, eli lilly, galapagos, gilead, glaxosmithkline, novartis, pfizer, regeneron, roche, sanofi, and ucb; research: bristol myers squibb and pfizer • lh, rmk, and sb: employees and shareholders: bristol myers squibb • dt: grant/research support, consultant, scientific advisory board, and speakers bureau: abbvie, almirall, amgen, biogen idec, boehringer ingelheim, bristol myers squibb, eli lilly, galapagos, galderma, janssen-cilag, leo pharma, novartis, pfizer, regeneron, roche, sandoz-hexal, sanofi, target-solution, and ucb figure 1. mechanism of action of deucravacitinib • ≥100-fold greater selectivity for tyk2 vs jak 1/3 • ≥2000-fold greater selectivity for tyk2 vs jak 2 deucravacitinib (allosteric inhibitor) unique tyk2 regulatory domain catalytic domain (highly conserved across jak family) atp-binding active site (other kinase inhibitors) tyk2 selectivity in cells1,9: atp, adenosine 5′-triphosphate; jak, janus kinase; tyk2, tyrosine kinase 2. table 1. baseline patient demographics and disease characteristics parameter poetyk pso-1 + pso-2 + lte deucravacitinib (n = 1519) age, mean (sd), y 46.6 (13.4) weight, mean (sd), kg 90.6 (21.6) body mass index, mean (sd), kg/m2 30.5 (6.8) female, n (%) 493 (32.5) race, n (%) white 1325 (87.2) asian 153 (10.1) black or african american 23 (1.5) other 18 (1.2) age at disease onset, mean (sd), y 28.8 (14.9) disease duration, mean (sd), y 18.7 (12.7) pasi, mean (sd) 21.1 (8.1) spga, n (%) 3 (moderate) 1211 (79.7) 4 (severe) 308 (20.3) bsa involvement, mean (sd), % 26.2 (15.8) bsa, body surface area; lte, long-term extension; pasi, psoriasis area and severity index; spga, static physician’s global assessment. microsoft word 6. 647 proof done.docx skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 34 resident competition research articles the perception of chemotherapy-induced alopecia in cancer patients currently undergoing treatment margit juhász, md,1* jamie fortman, msc,2* jessica lin, md,2 yessica landaverde,1 joshua levy, md,2 christine pham, bs,1,2 nicole myers, mph,2 chloe ekelem, md,1 ritesh parajuli, md,3 lari wenzel, phd,2,4 natasha atanaskova mesinkovska, md, phd1 1 university of california-irvine, department of dermatology, irvine, ca, usa 2 university of california-irvine, school of medicine, irvine ca, usa 3 university of california-irvine, division of hematology/oncology, department of medicine, irvine, ca, usa 4 university of california-irvine, department of medicine, biobehavioral shared resource of chao family comprehensive cancer center, irvine ca, usa *these authors contributed equally to this work. background: chemotherapy-induced alopecia (cia) is a common adverse effect of chemotherapy. eight percent of patients consider declining chemotherapy due to cia risk. objective: to determine whether cancer patients who are actively receiving chemotherapy are interested in preventing or treating cia. materials and methods: this is a survey-based, cross-sectional study of cancer patients undergoing chemotherapy infusion at a tertiary medical center. data including demographics, cancer diagnosis, medical literacy, quality of life, hair quality satisfaction, and costs patients were willing to accrue for cia prevention/treatment were gathered. results: sixty-two adults were enrolled, mostly 55 to 64 years of age, female (72.6%), and caucasian (63.8%). many patients were diagnosed with malignancies associated with a high rate of morbidity-mortality including ovarian, lung and pancreatic. in our cohort, all patients would not decline cancer treatment based on cia risk. 94.6% of patients were unwilling to risk cancer recurrence, 80.9% additional side effects, 55.8% extra time outside of infusion and 47.9% to pay out-of-pocket for cia prevention/treatment. conclusions: patients with high cancer disease burden will not decline current treatment due to cia risk. in addition, they are not willing to sustain additional discomfort, cost or time to prevent or treat cia. abstract skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 35 chemotherapy-induced alopecia (cia) is among the five most common adverse events related to cancer treatment with 22% to 65% of chemotherapy patients experiencing anagen effluvium.1-3 it is reported that 8% of patients consider declining chemotherapy due to cia risk.7 although most cia does not result in permanent hair loss, hair often grows back with altered color, texture, and density.2,4-6 cia can be devastating for patients and quality of life (qol) suffers because hair is used for personal expression and characterizes youth, health, beauty, religion and gender identity.8 women are more impacted than men by cia.9,10 patients react differently to cia depending on their values, cancer prognosis, degree of expected hair loss, physician counselling, and individual coping.4,8 even if the hair loss itself is not upsetting, the constant reminder of illness can be overwhelming.2,4 self-esteem declines after cancer diagnosis, and perception of body image can be exacerbated by cia.3 it is difficult to differentiate cia-related distress from confounding factors, such as poor cancer prognosis or treatment side effects, and may contribute to lack of significantly increased qol in patients receiving cia preventive measures. many chemotherapeutics, including some targeted therapies, cause cia. more than 80% of patients receiving anti-microtubule agents experience cia; the incidence of alopecia is > 60% with alkylators, 60% to 100% with topoisomerase inhibitors, and 10% to 50% with anti-metabolites. epidermal growth factor receptor inhibitors (egfri) cause hair loss in 50% to 90%. permanent cia after taxanes and egfri has been reported.11 the goal of this cross-sectional study is to determine cancer patients’ baseline knowledge of cia, the effect cia has on patients, the general interest in receiving cia prevention/treatment, and costs patients are willing to accrue for therapy. ethical review this study was approved by the university of california, irvine institutional review board and chao comprehensive cancer center skin disease-oriented team. study participants and data collection participant enrollment took place over 24 weeks from december 2017 to may 2018. english-speaking, adult patients, currently undergoing chemotherapy infusion, who were able and willing to give verbal consent were enrolled. patients who could not speak or read english, felt too ill or were disinterested in participating were not enrolled. study data were collected and analyzed using redcap (research electronic data capture).21 survey instrument after reviewing cia literature, three surveys were developed addressing demographics, hair quality satisfaction before and after cia, qol, as well as knowledge of cia and cia prevention/treatment (appendix 1). participants were asked what they would tolerate to minimize or treat cia including time, side effects, cost, and cancer recurrence risk with predefined response categories. in cases where a 4-point likert scale could be used, we asked patients to pick answers ranging from “not at all,” “a little,” “quite a bit,” to “very much”. in addition, introduction materials and methods skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 36 we used the only known disease-specific survey, chemotherapy-induced alopecia distress scale (cads),22 to assess patient perceptions of body image and overall qol (appendix 2). demographic and clinical information sixty-two patients currently undergoing chemotherapy infusion were enrolled. the majority of participants were female (72.6%), with a mean age range 55 to 64 years. annual household income ranged from < $25,000 usd (32.0%) to > $200,000 usd (12.0%). all patients were covered by medical insurance, were satisfied with coverage, and were undergoing traditional or targeted chemotherapy for cancer. the most common malignancy was ovarian (16.1%), followed by lung (11.3%), leukemia/lymphoma (11.3%) and pancreas (8.1%); a large proportion of patients were diagnosed with advanced malignancies associated with a high level of disease burden, morbidity and mortality. the most common chemotherapeutics used were carboplatin, cisplatin, oxaliplatin (38.7%), followed by docetaxel, paclitaxel (29.0%) and gemcitabine (17.7%) (figures 1 and 2). hair characteristics after chemotherapy prior to chemotherapy, 46.8% of patients were “very much” satisfied with their hair. only four patients had alopecia before starting chemotherapy [alopecia areata (n=2), lichen planopilaris (n=1) and androgenetic alopecia (n=1)]. forty-three patients (76.8%) experienced alopecia after starting chemotherapy, with 70.7% reporting hair loss involving the entire scalp; 60.8% of patients reported greater than 50% loss of hair. cia-associated symptoms included itching (32.1%), flaking and pimples (16.1% each), burning (14.8%), as well as pain, erythema and bumps (14.3% each); 48.2% of patients did not report symptoms. of the patients that answered “have you experienced hair regrowth on your scalp?” (n=34), 61.8% reported “yes.” hair regrew brown (35%), black (30%) or gray (30%), with the same or thinner thickness (45% each), and with the same texture (58.8%). only 16.7% of patients each reported “very much” and “quite a bit” satisfaction with their hair regrowth, with 45.8% being only “a little” satisfied. chemotherapy-induced alopecia distress scale the majority of patients who participated in cads answered either “not at all” or “a little” more frequently than “quite a bit” or “very much” for the entire questionnaire demonstrating that patients were not distressed by cia (figure 3). hair loss treatment knowledge despite having medical insurance, 77.4% of patients did not know if alopecia treatment costs were covered; of patients who knew their coverage, all patients reported that cia treatment or prevention would not be covered. 88.1% of patients reported that someone did inform them about cia-risk, most often by their oncologist (86.3%), but also the oncology nurse (25.5%), family/friends (23.5%), primary care physician (13.7%) or conducting their own research (13.7%); however, 33.4% reported being “a little” or “not at all” informed regarding cia and 47.3% reported not being aware of cia prevention/treatment. surprisingly, 11.5% of patients reported the expectation that their hair would not regrow after chemotherapy; of those reporting their hair would regrow, 88.5% thought it would regrow differently than before. the majority of results erythema and bumps (14.3% each); 48.2% of patients did not report symptoms. of the patients that answered “have you experienced hair regrowth on your scalp?” (n=34), 61.8% reported “yes.” hair regrew brown (35%), black (30%) or gray (30%), with the same or thinner thickness (45% each), and with the same texture (58.8%). only 16.7% of patients each reported “very much” and “quite a bit” satisfaction with their hair regrowth, with 45.8% being only “a little” satisfied. chemotherapy-induced alopecia distress scale the majority of patients who participated in cads answered either “not at all” or “a little” more frequently than “quite a bit” or “very much” for the entire questionnaire demonstrating that patients were not distressed by cia (figure 3). hair loss treatment knowledge despite having medical insurance, 77.4% of patients did not know if alopecia treatment costs were covered; of patients who knew their coverage, all patients reported that cia treatment or prevention would not be covered. 88.1% of patients reported that someone did inform them about cia-risk, most often by their oncologist (86.3%), but also the oncology nurse (25.5%), family/friends (23.5%), primary care physician (13.7%) or conducting their own research (13.7%); however, 33.4% reported being “a little” or “not at all” informed regarding cia and 47.3% reported not being aware of cia prevention/treatment. surprisingly, 11.5% of patients reported the expectation that their hair would not regrow after chemotherapy; of those reporting their hair would regrow, 88.5% thought it would regrow differently than before. the majority of patients were “not at all” aware of hair loss therapies such as scalp-cooling (71.9%), hormonal treatments (83.9%), injections skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 37 figure 1. patient-reported cancer type (n=62 patients, 70 malignancies). the most common “other” malignancy types were cervical (n=3) and multiple myeloma (n=3). (85.7%), immunosuppressants (90.9%), or topical and/or over-the-counter treatments (54.7%). however, subjects were most knowledgeable about head coverings, such as wigs or wraps, with 61.4% of patients answering they knew “very much” or “quite a bit”. hair loss treatment interest a majority of patients undergoing chemotherapy (64.9%) reported they were not interested in alopecia treatments. only 13 participants (21%) continued past the initial question to fully complete this survey section which included measures to discern interest in specific alopecia treatments. of those that responded, 46.2%, 69.2%, 61.5%, and 79% were “not at all” interested in scalp-cooling, hormones, injections, and immunosuppressants, respectively. on the other hand, 46.6% and 60% of patients were “very much” or “quite a bit” interested in topical and/or over-the-counter treatments and head coverings, respectively (figure 4). acceptable risks to minimize hair loss while a large proportion of patients were not willing to dedicate additional money (47.9%) or time outside of chemotherapy (58.8%) to minimize hair loss, 31.3% were willing to dedicate less than $100 and 26.1% were willing to temporarily dedicate time to treatment. patients were also unwilling to endure additional side effects (80.9%) or cancer recurrence (94.6%). as compared to previous data that 8% of patients would decline chemotherapy due to cia, 0% of our participants would have declined chemotherapy (table 1). skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 38 figure 2. patient-reported chemotherapeutic regimen (n=62 patients, 111 chemotherapeutics used). those chemotherapy regimens marked with an (*) indicate > 60% frequency of cia.11 skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 39 figure 3. the cads demonstrates that the majority of patients participating in this survey were “not at all” distressed by their cia. skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 40 figure 4. although the majority of patients report prior counselling regarding cia-risk, knowledge of cia prevention/treatment is lacking. patients are not interested in undergoing further prevention/treatment of cia except using either head coverings or topical/over-the-counter products. skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 41 table 1. although this population of patients is not well-educated regarding cia prevention/treatment, these results indicate that they are not interested or motivated to spend money or time on these modalities. no. of patients (n) percent (%) would you have declined chemotherapy if you had known about the risk of hair loss? (n=56) no 56 100% what is the highest chance of cancer recurrence you would be willing to risk for at least 50% reduction in hair loss? (n=56) not willing to risk cancer recurrence 53 94.6 1%-10% or 11%-20% or >75% 1 each 1.8 each 21%-30% or 31%-50% or 51%-75% 0 0 if there was an acceptable treatment to reduce you hair loss by at least 50%, what side effects would you be willing to endure? (n=47) none 38 80.9 change in appetite 4 8.5 change in weight 3 6.4 increased body or facial hair 3 6.4 skin rash or nausea, vomiting or diarrhea or headache or anxiety, depression or confusion 1 each 2.1 each sleep changes or increased risk of infection 0 0 if there was an acceptable treatment that could reduce your hair loss by at least 50% but was not covered by insurance, how much would you be willing to pay out-ofpocket per month? (n=48) nothing 23 47.9 <$20 7 14.6 $20-49.99 6 12.5 $50-99.99 2 4.2 $100-199.99 5 10.4 $200-499.99 3 6.3 $500-999.99 1 2.1 $1000-1,999.99 0 0 $2000 + 1 2.1 if at least 50% reduction in hair loss is not acceptable for an out-of-pocket cost, what percentage of reduction would be acceptable? (n=23) 50-60% 12 52.2 61-70% 4 17.4 71-80% 2 8.7 81-90% 3 13.0 91-100% 2 8.7 how much time would you dedicate to reducing hair loss by at least 50%? (n=47) none 18 38.8 during chemotherapy infusions 8 17.0 temporary once daily application or ingestion 8 17.0 temporary twice daily application or ingestion 9 19.1 monthly office visits 7 14.9 lifelong twice daily application of ingestion 4 8.5 lifelong once daily application or ingestion 3 6.4 weekly office visits 2 4.3 skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 42 while multiple studies have attempted to quantify cia’s impact on cancer patients’ qol, few assess the “value” of hair to individuals undergoing chemotherapy in terms of adverse events, time and monetary worth. according to the current literature, although 58% of patients expect cia to be the worst adverse event of chemotherapy, only 21.7% rate cia the worst after completing cancer treatment;26 however, up to 8% of patients would decline chemotherapy had they known about cia.7 the findings from this study did not support the previous claim as all participants reported they would not have turned down treatment due to cia risk. possible factors contributing to these contradictory data include our unique study population in which all patients were covered by medical insurance, currently undergoing chemotherapy infusion, and did not report distress from cia. our study location was a tertiary, academic medical center located in southern california which predisposed our patient population to be one diagnosed with a large proportion of high morbidity-mortality cancers, including but not limited to ovarian, lung, and pancreatic. the patients’ prognosis may have influenced their decision to receive chemotherapy regardless of adverse events including cia. another factor that may have significantly contributed to our participants lack of desire for cia prevention/treatment or associated risks is the relatively minimal distress caused by cia as measured by cads. patient answers may have been biased because only those feeling energetic and healthy participated in the survey. patients too tired or sick during infusion turned down participation, thus skewing cads results. given that our patients were minimally distressed by cia, it is understandable that they were not willing to undergo further side effects, or monetary/time investments to prevent alopecia or promote regrowth. of patients willing to pay out-of-pocket, 60% would pay < $100 usd/month, which is consistent with a previous willingness-to-pay study of non-small cell lung cancer patients undergoing chemotherapy in which women were willing to pay as much as 2.1% of their annual income to reduce cia.25 given an average $30,000 usd annual income, 2% would be $50 usd/month. unsurprisingly, given their active malignant disease burden, the majority of our patients did not want cia prevention/treatment to be accompanied by additional adverse effects. the side effects that a small number of patients were willing to endure included change in weight or appetite and increased facial or body hair. additionally, our patients were not interested in spending extra time for cia-prevention. for instance, scalp-cooling requires 30 minutes prior to, the entire time during, and 90 to 120 minutes post-infusion;15,16 based on our patient preferences this seems undesirable. there is an existing knowledge gap in potential cia prevention/treatment amongst medical providers and patients which needs to be addressed. our data correlates with other studies assessing cia therapy knowledge, in which 73% of patients never heard of scalp-cooling, the most recent breakthrough in cia-prevention, and oncologists reported insufficient knowledge regarding alopecia treatments including scalp-cooling.23 patients’ lack of knowledge regarding cia prevention/treatment may have significantly contributed to our findings. subgroup analysis did not demonstrate any differences in cia views based on presumed cancer prognosis. we also compared our results from patients actively receiving discussion skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 43 cancer treatment to a small cohort of patients (n=5), from the same tertiary medical center, who were currently in remission from breast cancer, multiple myeloma and/or leukemia/lymphoma. universally, patients in remission reported they would have not turned down chemotherapy because of ciarisk and were also not willing to endure extra monetary cost, time or effort for cia prevention/treatment. limitations of this study include difficulty in standardizing results as not all questions were answered by all patients, recall bias and selection bias. the average participant response rate was 60.5%, with the hypothesis that more emotionally taxing or sensitive areas of the survey resulted in lower response rate. the sections of the survey with lowest response were in the middle which does not correlate with respondent fatigue. the survey was initially meant to completed electronically with sections being skipped had the patient answered “no” to the first question. unfortunately, given infection control within the infusion unit, it was only possible to administer the survey in paper format, thus negatively impacting our response rate. only english-speaking participants were enrolled to complete this english-only survey. because many patients reported experiencing some hair loss, a significant control group to compare ciadistress as measured by cads is lacking. cia undeniably affects qol and should not be ignored. however, in patient populations with high morbidity-mortality cancers currently receiving chemotherapy, concerns for cia may not be as impactful as previously thought. poor prognosis may influence the decision to receive treatment despite adverse events such as cia, contributes to a lack of distress despite losing hair, and explains the hesitance to obtain cia prevention/treatment with possible further adverse effects. future studies to obtain information from patients who completed chemotherapy, are awaiting chemotherapy initiation, and/or are using cia-preventive measures, such as scalpcooling, need to be completed to see if the results will differ from our patient cohort. keywords: chemotherapy-induced alopecia, chemotherapy, hair loss, quality of life, prevention, cost-effectiveness abbreviation and acronym list: cads = chemotherapy-induced alopecia distress scale cia = chemotherapy-induced alopecia egfri = epidermal growth factor receptor inhibitor fda = food and drug administration qol = quality of life redcap = research electronic data capture us = united states usd = united states dollar conflict of interest disclosures: none funding: none corresponding author: margit juhasz, md department of dermatology and dermatopathology, university of california-irvine gottschalk medical plaza, 1 medical plaza drive, irvine, ca, 92697 phone: 949-824-7103 fax: 949-824-8954 email: mjuhasz@hs.uci.edu references: 1. lemieux j, maunsell e, provencher l. chemotherapy-induced alopecia and effects on quality of life among women with breast cancer: a literature review. psychooncology. 2008;17(4):317-328. 2. beisecker a, cook mr, ashworth j, et al. side effects of adjuvant chemotherapy: perceptions of conclusion skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 44 node-negative breast cancer patients. psychooncology. 1997;6(2):85-93. 3. munstedt k, manthey n, sachsse s, vahrson h. changes in self-concept and body image during alopecia induced cancer chemotherapy. support care cancer. 1997;5(2):139-143. 4. robinson a, jones w. changes in scalp hair after cancer chemotherapy. eur j cancer clin oncol. 1989;25(1):155-156. 5. kanti v, nuwayhid r, lindner j, et al. analysis of quantitative changes in hair growth during treatment with chemotherapy or tamoxifen in patients with breast cancer: a cohort study. br j dermatol. 2014;170(3):643-650. 6. lindner j, hillmann k, blume-peytavi u, et al. hair shaft abnormalities after chemotherapy and tamoxifen therapy in patients with breast cancer evaluated by optical coherence tomography. br j dermatol. 2012;167(6):1272-1278. 7. tierney a, taylor j. chemotherapy-induced hair loss. nurs stand. 1991;5(38):29-31. 8. batchelor d. hair and cancer chemotherapy: consequences and nursing care--a literature study. eur j cancer care (engl). 2001;10(3):147163. 9. nozawa k, shimizu c, kakimoto m, et al. quantitative assessment of appearance changes and related distress in cancer patients. psychooncology. 2013;22(9):2140-2147. 10. fink b, hufschmidt c, hirn t, will s, mckelvey g, lankhof j. age, health and attractiveness perception of virtual (rendered) human hair. front psychol. 2016;7:1893. 11. rubio-gonzalez b, juhasz m, fortman j, mesinkovska na. pathogenesis and treatment options for chemotherapy-induced alopecia: a systematic review. int j dermatol. 2018. 12. mcgarvey el, leon-verdin m, baum ld, et al. an evaluation of a computer-imaging program to prepare women for chemotherapy-related alopecia. psychooncology. 2010;19(7):756-766. 13. williams j, wood c, cunningham-warburton p. a narrative study of chemotherapy-induced alopecia. oncol nurs forum. 1999;26(9):14631468. 14. duvic m, lemak na, valero v, et al. a randomized trial of minoxidil in chemotherapyinduced alopecia. j am acad dermatol. 1996;35(1):74-78. 15. nangia j, wang t, osborne c, et al. effect of a scalp cooling device on alopecia in women undergoing chemotherapy for breast cancer: the scalp randomized clinical trial. jama. 2017;317(6):596-605. 16. rugo hs, klein p, melin sa, et al. association between use of a scalp cooling device and alopecia after chemotherapy for breast cancer. jama. 2017;317(6):606-614. 17. kiebert gm, hanneke j, de haes cj, kievit j, van de velde cj. effect of peri-operative chemotherapy on the quality of life of patients with early breast cancer. eur j cancer. 1990;26(10):1038-1042. 18. hershman dl. scalp cooling to prevent chemotherapy-induced alopecia: the time has come. jama. 2017;317(6):587-588. 19. van den hurk cj, van den akker-van marle me, breed wp, van de poll-franse lv, nortier jw, coebergh jw. cost-effectiveness analysis of scalp cooling to reduce chemotherapy-induced alopecia. acta oncol. 2014;53(1):80-87. 20. fehr mk, welter j, sell w, jung r, felberbaum r. sensor-controlled scalp cooling to prevent chemotherapy-induced alopecia in female cancer patients. curr oncol. 2016;23(6):e576-e582. 21. harris pa, taylor r, thielke r, payne j, gonzalez n, conde jg. research electronic data capture (redcap)--a metadata-driven methodology and workflow process for providing translational research informatics support. j biomed inform. 2009;42(2):377-381. 22. cho j, choi ek, kim ir, et al. development and validation of chemotherapy-induced alopecia distress scale (cads) for breast cancer patients. ann oncol. 2014;25(2):346-351. 23. peerbooms m, van den hurk cj, breed wp. familiarity, opinions, experiences and knowledge about scalp cooling: a dutch survey among breast cancer patients and oncological professionals. asia pac j oncol nurs. 2015;2(1):35-41. 24. freedman tg. social and cultural dimensions of hair loss in women treated for breast cancer. cancer nurs. 1994;17(4):334-341. 25. bernard m, brignone m, adehossi a, et al. perception of alopecia by patients requiring chemotherapy for non-small-cell lung cancer: a willingness to pay study. lung cancer. 2011;72(1):114-118. 26. tierney aj, taylor j, closs sj. knowledge, expectations and experiences of patients receiving chemotherapy for breast cancer. scand j caring sci. 1992;6(2):75-80. skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 45 appendix 1a: demographic and health information. what is your age? □ 18-24 years old □ 25-34 years old □ 35-44 years old □ 45-54 years old □ 55-64 years old □ 65-74 years old □ 75 years or older biological sex □ female □ male □ intersex gender identity □ female □ male sexual orientation □ asexual □ bisexual □ heterosexual □ homosexual □ other marital status □ divorced □ living together □ married □ separate □ single □ widowed □ unknown/decline to state race □ american indian/alaska native □ asian □ middle eastern □ native hawaiian or other pacific islander □ black or african american □ white □ unknown ethnicity □ hispanic or latino □ not hispanic or latino □ unknown/not reported religious preferences □ buddhism □ christianity □ hinduism □ irreligion (atheist or agnostic) □ islam □ judaism □ non-affiliated □ other what is the highest degree of level of school you have completed? if currently enrolled, mark the previous grade or highest degree received. □ 8th grade or less □ 9-11th grade □ high school graduate/ged □ vocational/technical school □ associate degree/some college □ bachelor’s degree □ advanced degree (md, phd, master’s) □ unknown/declined to state employment status □ employed for wages □ self-employed □ unemployed skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 46 □ homemaker □ disabled □ retired □ unknown/declined to state what is your total household income? □ less than $25,000 □ $25,000 to $49,999 □ $50,000 to $74,999 □ $75,000 to $99,999 □ $100,000 to $149,999 □ $150,000 to $199,999 □ $200,000 or more do you have health insurance? □ yes □ no do you have children? □ yes □ no what age are your children? □ less than 5 years old □ 5 to 10 years old □ 11 to 17 years old □ 18 years or older frequency of exercise □ once a week □ 2-3 times a week □ 4-6 times a week □ daily □ rarely □ other details: ________________________________________ dietary restrictions □ vegetarian □ vegan □ gluten free □ other □ none details: ________________________________________ medical history what type of cancer were you diagnosed with? you may check multiple boxes. □ bladder cancer □ breast cancer □ colon and rectal cancer □ endometrial cancer □ kidney cancer □ leukemia/lymphoma □ liver cancer □ lung cancer □ melanoma □ non-hodgkin lymphoma □ pancreatic cancer □ prostate cancer □ thyroid cancer □ other if you indicated other type, what is the type of cancer you were diagnosed with? ________________________________________ was your most recent cancer diagnosis an initial diagnosis, recurrent diagnosis, or second type of cancer diagnosis? □ initial diagnosis □ recurrent diagnosis □ second type of cancer what is the status of your cancer? □ active □ stable □ in remission skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 47 □ recurrence are you currently receiving treatment for cancer? □ yes □ no please indicate which chemotherapies you are (or were) treated with for your cancer. you may check multiple boxes. □ none □ cetuximab, canertinib, erlotinib, gefitinib, lapatinib, or panitumumab □ methotrexate □ bendamustine, cyclophosphamide, estramustine, ifosfamide, mechloretamine, or melphalan □ carboplatin, cisplatin, or oxaliplatin □ 6-mercaptopurine, 6-thioguianine, azathioprine, or fludarabine □ 5-fluorouracil, capecitabine, or cytarabine □ vemurafenib or dabrafenib □ paclitaxel or docetaxel □ topotecan or irinotecan □ etoposide, teniposide, or mitoxantrone □ dacarbazine, procarbazine, or temozolomide □ sorafenib or sunitib □ vincristine, cinblastine, vinorelbine, vinflunine □ other what other chemotherapy agents were part of your treatment regimen? ________________________________________ why are you not currently receiving treatment? □ i am waiting for my treatments to start □ i completed my treatment regimen □ i declined treatment other medical problems? you may check multiple boxes. □ alopecia (hair loss) □ high blood pressure □ celiac’s disease □ diabetes □ eczema □ endometriosis □ lupus □ obstructive sleep apnea □ ovarian cyst □ psoriasis □ rheumatoid arthritis □ thyroid disease have you been on hormone replacement therapy? □ yes □ no menstrual status □ pre-menopausal □ peri-menopausal □ post-menopausal age at start of menopause (give best estimate). ________________________________________ please check the boxes for known family history. □ alopecia (hair loss) □ cancer □ thyroid disease skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 48 appendix 1b: hair information. natural hair details please choose the options that best describe your hair prior to any chemotherapy treatments or hair loss. what is your natural hair color? □ blonde □ brown □ red □ black □ gray □ white □ no hair how much hair did you have prior to your cancer treatment (hair density)? □ thick □ medium □ thin how thick was each strand of hair prior to your cancer treatment (hair diameter)? medium is approximately the diameter of a piece of thread. □ coarse □ medium □ fine what is your natural hair texture? □ straight □ curly □ wavy □ other how long was your hair prior to chemotherapy and/or hair loss? □ hair ended above chin □ hair ended above shoulders □ hair ended above armpits □ hair ended above belly button □ hair ended at or below belly button how satisfied were you with your hair prior to receiving cancer treatment? □ not at all □ a little □ quite a bit □ very much history of alopecia (hair loss) were you diagnosed with alopecia (hair loss) before cancer treatment started? □ yes □ no what type of alopecia were you diagnosed with? you may check multiple boxes. □ alopecia areata □ central centrifugal cicatricial alopecia □ frontal fibrosing alopecia □ lichen planopilaris □ patterned hair loss (androgenic, androgenetic, male patterned, female patterned) □ telogen effluvium □ traction alopecia □ other what type of other alopecia were you diagnosed with? ________________________________________ does anyone else in your family have a history of alopecia (hair loss)? □ yes □ no □ unknown if so, who? you may check multiple boxes. □ mother □ father □ sister □ brother □ son □ daughter skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 49 what type of alopecia is in your family history? you may check multiple boxes. □ alopecia areata □ central centrifugal cicatricial alopecia □ frontal fibrosing alopecia □ lichen planopilaris □ patterned hair loss (androgenic, androgenetic, male patterned, female patterned) □ telogen effluvium □ traction alopecia □ other do you have any surgical scars on scalp? □ yes □ no □ unknown chemotherapy-induced alopecia have you experienced hair loss after cancer treatment started? □ yes □ no have you experienced any of these types of hair loss after chemotherapy started? you may check multiple boxes. □ none □ shedding □ thinning □ breakage □ not growing □ unknown location of most hair loss on scalp after chemotherapy started? you may check multiple boxes. □ front scalp □ bald patches □ top of head □ entire scalp □ other □ unknown what percentage of hair did you lose? □ no hair loss □ less than 25% hair loss □ 25% to 50% hair loss □ 51% to 75% hair loss □ more than 75% hair loss have you experienced hair loss in places other than your scalp? □ yes □ no where have you experienced hair loss other than your scalp? you may check multiple boxes. □ arms or legs □ chest, back or abdomen □ eyebrows □ eyelashes □ nose hair □ pubic area □ underarms have you experienced any associated scalp symptoms? you may check multiple boxes. □ itching □ burning □ pain □ redness □ flaking □ bumps □ pimples □ none □ other itching □ mild □ moderate □ severe burning □ mild □ moderate skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 50 □ severe pain □ mild □ moderate □ severe redness □ mild □ moderate □ severe flaking □ mild □ moderate □ severe bumps □ mild □ moderate □ severe pimples □ mild □ moderate □ severe have you experienced hair regrowth on your scalp? □ yes □ no □ unknown hair color after regrowth? □ blonde □ brown □ red □ black □ gray □ other hair density after regrowth? □ thicker □ thinner □ same hair diameter after regrowth? □ more coarse □ more fine □ same hair texture after regrowth? □ more curly □ more wavy □ more straight □ same after you completed your chemotherapy regimen, when did regrowth start? □ still receiving chemotherapy □ less than 1 month □ 1 month to 3 months □ 3 months to 6 months □ 6 months to 1 year □ 1 year to 2 years □ more than 2 years how much of your hair has regrown as compared to your hair before cancer treatment? □ less than 25% □ 25% to 50% □ 51% to 50% □ more than 75% how satisfied are you with your hair after it has regrown? □ not at all □ a little □ quite a bit □ very much hair care practices previous hair care? you may check multiple boxes. □ curly perm □ relaxer □ coloring □ blow dryer skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 51 □ hot iron/curling iron/flat iron □ hot comb □ hot rollers □ braids □ weave □ other □ unknown other previous hair care treatments? ________________________________________ did you shave your head or do you plan to? □ yes □ no when did you shave your head or when are you planning on shaving your head? □ before chemotherapy starts □ before hair loss starts □ once hair loss starts □ after a significant amount of hair is lost do you or did you wear anything that covers your head? you may check multiple boxes. □ none □ wrap □ har □ wig □ extensions □ other details: ________________________________________ skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 52 appendix 1c: hair loss treatment options. did someone talk to you about the risk of hair loss due to chemotherapy? □ yes □ no who discussed the risk of hair loss with you? you may check multiple boxes. □ primary care physician □ oncologist □ patient educators □ nurse □ support groups □ family and/or friends □ research on your own did you feel well-informed about hair loss? □ not at all □ a little □ quite a bit □ very much how much do you agree with the statements below? my hair will regrow the same as it was before cancer treatment. □ not at all □ a little □ quite a bit □ very much my hair will regrow, but it will regrow different than it was before cancer treatment. □ not at all □ a little □ quite a bit □ very much my hair will not regrow. □ not at all □ a little □ quite a bit □ very much are you aware about hair loss treatments? □ yes □ no are you aware about these hair loss treatments, including the procedure and cost? scalp cooling □ not at all □ a little □ quite a bit □ very much hormones □ not at all □ a little □ quite a bit □ very much injections □ not at all □ a little □ quite a bit □ very much immunosuppressants □ not at all □ a little □ quite a bit □ very much topical and/or over-the-counter treatments □ not at all □ a little □ quite a bit □ very much head coverings (wigs or wraps) □ not at all □ a little □ quite a bit □ very much skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 53 are you interested in hair loss treatment? □ yes □ no are you interested in these hair loss treatments? scalp cooling □ not at all □ a little □ quite a bit □ very much hormones □ not at all □ a little □ quite a bit □ very much injections □ not at all □ a little □ quite a bit □ very much immunosuppressants □ not at all □ a little □ quite a bit □ very much topical and/or over-the-counter treatments □ not at all □ a little □ quite a bit □ very much head coverings (wigs or wraps) □ not at all □ a little □ quite a bit □ very much if there was an acceptable treatment to reduce your hair loss by at least 50%, what side effects would you be willing to endure? you may check multiple boxes. □ none □ increased body or facial hair □ anxiety, depression, or confusion □ change in appetite □ change in weight □ nausea, vomiting, or diarrhea □ headaches □ skin rash □ changes in sleep □ increased risk of infection if you have insurance, does your insurance cover the cost of hair loss treatments? □ yes □ no □ i do not know □ i do not have insurance if there was an acceptable treatment that could reduce your hair loss by at least 50% but was not covered by insurance, how much would you be willing to pay out of pocket per month? □ nothing □ less than $20 □ $20 to $49.99 □ $50 to $99.99 □ $100 to $199.99 □ $200 to $499.99 □ $500 to $999.99 □ $1000 to $1999.99 □ $2000 or more if at least 50% reduction in hair loss is not acceptable for an out of pocket cost, what percentage would be acceptable? □ 50% to 60% □ 61% to 70% □ 71% to 80% □ 81% to 90% □ 91% to 100% skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 54 how much time would you dedicate to reducing hair loss by at least 50%? you may check multiple boxes. □ none □ during chemotherapy infusions □ temporary once daily application or ingestion □ temporary twice daily application or ingestion □ lifelong once daily application or ingestion □ lifelong twice daily application or ingestion □ weekly office visits □ biweekly office visits □ monthly office visits what is the highest change of cancer recurrence you would be willing to risk for at least 50% reduction in hair loss? □ not willing to risk cancer recurrence □ 1% to 10% □ 11% to 20% □ 21% to 30% □ 30% to 50% □ 50% to 75% □ more than 75% risk of recurrence would you have declined chemotherapy if you have known about the risk of hair loss? □ yes □ no skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 55 appendix 2: chemotherapy-induced alopecia distress scale (cads). 22 physical the area is itching. □ not at all □ a little □ quite a bit □ very much the area is burning or prickling or resulting in pain. □ not at all □ a little □ quite a bit □ very much emotional i feel different from others. □ not at all □ a little □ quite a bit □ very much i am dissatisfied with my appearance. □ not at all □ a little □ quite a bit □ very much i lose confidence about the future. □ not at all □ a little □ quite a bit □ very much i am easily irritated and stressed. □ not at all □ a little □ quite a bit □ very much i feel depressed. □ not at all □ a little □ quite a bit □ very much i feel lonely. □ not at all □ a little □ quite a bit □ very much activity i have difficulty doing personal care such as bath and make-up. □ not at all □ a little □ quite a bit □ very much i experience limitations doing leisure activities. □ not at all □ a little □ quite a bit □ very much i feel sicker because of my hair loss. □ not at all □ a little □ quite a bit □ very much i do not like it when people find that i have cancer because of my hair loss. □ not at all □ a little □ quite a bit □ very much i have problems going out shopping and to restaurants. □ not at all □ a little skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 56 □ quite a bit □ very much i always wear a wig or scarf to hide hair loss. □ not at all □ a little □ quite a bit □ very much relationship i am worried about relationships with family and friends. □ not at all □ a little □ quite a bit □ very much i am worries about my relationship with my spouse or partner. □ not at all □ a little □ quite a bit □ very much i am worried about my sexual relationship with my spouse or partner. □ not at all □ a little □ quite a bit □ very much the efficacy and safety of aminolevulinic acid 20% topical solution activated by pulsed dye laser and blue light for the treatment of facial cutaneous squamous cell carcinoma in situ mark s nestor1–3; haowei han1; faraz yousefian1; ciaran smythe1 1center for clinical and cosmetic research, aventura, fl; 2department of dermatology and cutaneous surgery, university of miami miller school of medicine, miami, fl; 3department of surgery, division of plastic surgery, university of miami miller school of medicine, miami, fl introduction • squamous cell carcinoma (scc) is the second most common cutaneous malignancy1 • aminolevulinic acid (ala) 20% solution–photodynamic therapy (ala-pdt) is approved for the treatment of actinic keratoses on the face, scalp, and upper extremities2 and is a potential treatment option for scc objective • this study evaluated the efficacy, tolerability, and safety of ala-pdt in combination with pulsed dye laser (pdl) for the treatment of facial cutaneous scc in situ (isscc) methods study design and participants • a prospective, single-center, investigator-initiated, open-label pilot clinical trial (nct02137785) was conducted at the center for clinical and cosmetic research in 2020–2021 • patients with biopsy-confirmed isscc on the face were included in the study • only lesions with a diameter of 0.4–1.3 cm were considered for the study • patients with infiltrative, severe, metaplastic, or recurrent isscc were excluded from the study figure 1. imaging of isscc in 2 patients obtained (a) before and (b) after treatment with ala-pdl-pdt a) visit 1 (pretreatment) patient a patient b b) visit 10 (posttreatment) patient a patient b a) visit 1 (pretreatment) patient a patient b b) visit 10 (posttreatment) patient a patient b ala, aminolevulinic acid; pdl, pulsed dye laser; pdt, photodynamic therapy; isscc, squamous cell carcinoma in situ. tolerability • median lsr scores peaked within 1 week following each treatment session and steadily decreased afterward (table 1) — the most common lsrs were erythema and scaling • the mean ± standard deviation posttreatment pain score was 2.95 ± 2.97 table 1. median local skin reaction scores for the lesion areas visit number 1 (pre-tx #1) 3 (tx #1) 4 5 6 (pre-tx #2) 7 (tx #2) 8 9 10 eot erythema 2 3 3 2 2 3 3 2 1 flaking/scaling 1 1 1 1 1 0.5 1 0.5 0 crusting 0 0 0 0 0 0 0 0.5 0 swelling 0 0 0 0 0 0 0 0 0 vesiculation/ pustulation 0 0 0 0 0 0 0 0 0 erosion/ ulceration 0 0 0 0 0 0 0 0 0 data shown as median lsrs for the lesion areas. responses were scored on a scale from 0 (not present) to 4 (high severity). eot, end of treatment; lsr, local skin reaction; tx, treatment. safety • the majority of treated patients (65%) did not experience any aes • reported aes included allergic contact dermatitis, blurry vision, right ear pain, right leg cellulitis, double vision, hypotension, and wound site infection — none of the reported aes were serious or considered related to study treatment • no patients withdrew from the study conclusions • the primary and secondary efficacy endpoints of histological and clinical clearance were achieved in a majority of patients by the end of ala-pdl-pdt treatment • ala-pdl-pdt was well tolerated and safe references 1) voiculescu v, et al. dis markers. 2016;2016:4517492. 2) levulan® kerastick® (aminolevulinic acid hcl) for topical solution, 20%. full prescribing information. sun pharmaceutical industries, inc. 2020. acknowledgments this investigator-initiated trial was funded by sun pharma. medical writing support was provided by alphabiocom, llc, and funded by sun pharma. disclosures mn received a research grant from sun pharma. hh, fy, and cs report nothing to disclose. treatments and procedures • ala 20% topical solution was applied to the lesion and adjacent skin and incubated for 18–24 hours, followed by pdl treatment (pulse duration: 0.45 milliseconds, fluence: 13 j/cm2, amount determined by the investigator) and then blue light illumination (blu-u®; 10 j/cm2 for 16 minutes 40 seconds) • patients underwent 2 ala-pdl-pdt treatment sessions separated by a 30-day period • the lesion was surgically excised for histological assessment 4–6 weeks following the second treatment assessments and endpoints • the primary efficacy endpoint was the proportion of patients achieving histological clearance of isscc at the end of treatment/surgical excision • tolerability was assessed from local skin reactions (lsrs) and patient-reported lesion site pain — lesion site pain was measured using a visual analog scale ranging from 0 (no pain) to 10 (worst pain possible) within 15 minutes of each treatment session • safety was assessed from frequency of adverse events (aes) results efficacy • of 20 enrolled patients, 17 (85%) achieved histological clearance at the end of treatment • after excluding two patients with residual isscc exhibiting skip lesions, the histological clearance rate was 17/18 patients (94%) • images obtained during visit 1 (pretreatment; figure 1a) and visit 10 (posttreatment; figure 1b) show clinical clearance of isscc with ala-pdl-pdt microsoft word 1. 792 proof done.docx skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 1 clinical management recommendations dermatology and vaccines: a call to arms shruti agrawal, md1 and kenneth j. tomecki, md1 1cleveland clinic, department of dermatology, cleveland, oh there are several dermatology-related vaccines – such as those directed against human papilloma virus (hpv), measles, mumps, and rubella (mmr), varicella, and herpes zoster. efficacy, safety, and costeffectiveness of vaccines are wellestablished, but significant controversy surrounds their use, with ongoing debate over their utility and side effects. the result is a vocal anti-vaccine movement that is threatening the health and welfare of millions. the world health organization (who) has included vaccine hesitancy, “the reluctance or refusal to vaccinate despite the availability of vaccines,” among the top ten health threats worldwide in 2019.1 this robust anti-vaccine movement continues to flourish, even though vaccines prevent 2-3 million deaths per year1 and can prevent and treat some cancers. for instance, the 9valent hpv vaccine (gardasil) is available in the united states. it protects against hpv 16 and 18, which account for at least 70% of cervical cancers,2 in addition to offering protection against hpv strains that cause anogenital warts. more than 30,000 hpvassociated cancers annually are caused by strains that are covered by the 9-valent vaccine.3 in addition to serving as a preventive tool, hpv vaccination may be an effective treatment for warts, basal cell carcinoma, and squamous cell carcinoma.5 the centers for disease control and prevention (cdc) recommends hpv vaccination for teenagers 11 to 12 years old – two doses at 6-12 months apart. immunization can occur as early as 9 years of age. for children 15 years or older, three doses are recommended. recently, the fda has approved the use of gardasil for men and women up to 45 years old, providing additional protection for adults who may not have been previously exposed to all 9 hpv types. the hpv vaccine should not be given to pregnant women, although pregnancy testing is not necessary before immunization. despite its benefits, overall acceptance of hpv vaccination has been modest at best, possibly due to lack of widespread availability of accurate information, a false perception that only sexually active adolescents should receive the vaccine, social stigma, financial barriers, and the need for multiple doses.6 some physicians present the hpv vaccine as “optional,” instead of firmly and clearly framing the vaccine as a non-negotiable tool to prevent disease. the mmr vaccine is another important vaccination in dermatology as it prevents measles, mumps, and rubella. the current recommendation is administrating two doses of the vaccine – the first at 12-15 months and the second at 4-6 years. a third dose can be skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 2 employed in target populations with a high risk of mumps.7 with widespread adoption of the mmr vaccine, measles was thought to have been eliminated in the united states as of 2000. however, the incidence of measles has risen drastically, in part due to the anti-vaccine movement and decrease in vaccination rates. more than 1200 cases of measles have been reported this year in the united states, the highest number since 1992.8 globally, the incidence of measles has increased by 30%.1 as a result, physicians, especially pediatricians and dermatologists, will see more patients, both children and adults, with measles. some vaccinations are less controversial than others. the recombinant herpes zoster vaccine (shingrix) has become popular, leading to supply shortages.9 the vaccine reduces the risk of herpes zoster dramatically, with greater than 90% efficacy in clinical trials.10 it also reduces the risk of post herpetic neuralgia. shingrix is recommended for healthy adults over the age of 50 years old, administered in two doses separated by 2 to 6 months.11 it is important to emphasize that vaccines are not just for children. many vaccines are recommended for adults, such as the herpes zoster vaccine, pneumococcal vaccine in those with certain co-morbidities, and a yearly influenza vaccine. the influenza vaccine is essential regardless of immunosuppression, as older adults account for the majority of influenza deaths in the united states. while many patients are worried about side effects, true allergic reactions, including anaphylaxis, are rare. most side effects are minor and include fever, localized injection site reaction, and rash. live vaccines including mmr, mmrv, varicella, liveattenuated influenza virus, live herpes zoster (zostavax), and bacille calmette-guérin (bcg), are contraindicated in immunosuppressed patients and in pregnant women. a standard practice is to delay vaccination in the presence of a moderate or severe acute illness. the cdc has a list of contraindications and precautions available on its website17 and also provides immunization schedules and patient education materials, a valuable tool for dermatologists to be familiar with. while strong evidence exists regarding the safety and efficacy of vaccinations, such information is not widely disseminated to the general public. social media is partially responsible for perpetuating anti-vaccination ideas, with common themes apparent – “trust” (suspicion of the scientific community), “alternatives” (a desire for a homeopathic approach instead of vaccination), “safety” (concern about risks of vaccinations), and “conspiracy” (suspicion that the government and others are hiding information about vaccines).12 to their credit, facebook13 and youtube14 have agreed to decrease the presence of the anti-vaccination platform on their websites. by providing targeted, accurate, and direct messaging, social media can be instrumental in combatting distorted information. additionally, the who provides modules to help guide discussions with patients and address anti-vaccination attitudes, even providing sample answers to commonly asked questions.16 along with appropriate counseling, dermatologists should direct patients to a primary care doctor, nearby clinic, or pharmacy where vaccines are available. vaccines are a safe, cost-effective way to reduce the risk of many infectious diseases. unfortunately, many physicians have assumed a passive role in promoting skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 3 vaccination, possibly due to lack of familiarity with individual vaccines or time constraints. despite these challenges, dermatologists must be advocates for vaccination and protect the health of patients. vaccination is absolutely essential to public health, and all physicians should consider vaccination a “call to arms.” physicians are a trusted and influential resource for patients and should be advocates and leaders in endorsing the role of vaccination in preventing disease and promoting overall health. they owe it to their patients, themselves, their families, and the greater good. it’s the right thing to do. period. conflict of interest disclosures: none funding: none corresponding author: kenneth j. tomecki, md cleveland clinic department of dermatology cleveland, oh email: tomeckk@ccf.org references: 1. akbar r. ten threats to global health in 2019. https://www.who.int/emergencies/ten-threats-toglobal-health-in-2019. 2. human papillomavirus (hpv) and cervical cancer. january 2019. https://www.who.int/newsroom/fact-sheets/detail/human-papillomavirus(hpv)-and-cervical-cancer. 3. hpv vaccine information for clinicians. https://www.cdc.gov/hpv/hcp/need-to-know.pdf. 4. mccormack pl. quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine (gardasil(®)): a review of its use in the prevention of premalignant anogenital lesions, cervical and anal cancers, and genital warts. drugs. 2014;74(11):1253-1283. doi:10.1007/s40265-014-0255-z 5. pham ct, juhasz m, sung c, mesinkovska na. the human papillomavirus vaccine as a treatment 1 for hpv-related dysplastic and neoplastic conditions: a literature review. j am acad dermatol. may 2019. doi:10.1016/j.jaad.2019.04.067 6. holman dm, benard v, roland kb, watson m, liddon n, stokley s. barriers to human papillomavirus vaccination among us adolescents: a systematic review of the literature. jama pediatr. 2014;168(1):76-82. doi:10.1001/jamapediatrics.2013.2752 7. marin m, temte j, snider d, seward j. use of combination measles, mumps, rubella, and varicella vaccine: recommendations of the advisory committee on immunization practices (acip). may 2010. https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5 903a1.htm. 8. measles cases and outbreaks. august 2019. https://www.cdc.gov/measles/casesoutbreaks.html. 9. current vaccine shortages & delays. https://www.cdc.gov/vaccines/hcp/clinicalresources/shortages.html#note3. 10. yancey kb. commentary regarding: efficacy of an adjuvanted herpes zoster subunit vaccine in older adults. h lal, al cunningham, o godeaux et al., n engl j med 372:2087-2096, 2015. dermatologic therapy. 2016;29(5):300-301. doi:10.1111/dth.12330 11. shingles vaccination. january 2018. https://www.cdc.gov/vaccines/vpd/shingles/public/ shingrix/index.html. 12. hoffman bl, felter em, chu k-h, et al. it’s not all about autism: the emerging landscape of antivaccination sentiment on facebook. vaccine. 2019;37(16):2216-2223. doi:10.1016/j.vaccine.2019.03.003 13. cohen e, bonifield j. facebook to get tougher on anti-vaxers. february 2019. https://www.cnn.com/2019/02/25/health/facebookanti-vaccine-content/index.html. 14. youtube takes ads off “anti-vax” video channels. february 2019. https://www.bbc.com/news/technology-47357252. 15. making an effective referral. august 2018. https://www.cdc.gov/hpv/hcp/making-referral.html. 16. addressing vaccine hesistancy. september 2018. https://www.who.int/immunization/programmes_sy stems/vaccine_hesitancy/en/. 17. contraindications and precautions: general best practice guidelines for immunization: best practices guidance of the advisory committee on immunization practices (acip). may 2019. https://www.cdc.gov/vaccines/hcp/aciprecs/general-recs/contraindications.html. evaluation of the safety and efficacy of ultherapy® for the treatment of signs and symptoms of erythematotelangiectatic rosacea rosalyn george, md1; joel schlessinger, md2; mark lupin, md3; david amato, md4; david mcdaniel, md5 1faad wilmington dermatology center; wilmington, nc; 2 faad, faacs lovelyskin; omaha, ne; 3 faad cosmedica; victoria, bc; 4 all about faces; hummelstown, pa; 5 faad laser and cosmetic center; virginia beach, va • it is hypothesized that creation of focal lesions in the dermis and sub-dermis may affect the symptoms of erythematotelangiectatic rosacea by inducing coagulation in superficial blood vessels and reducing blood flow in the skin background and objective • the study enrolled 88 subjects (79 female and 9 male) with a mean age of 49.8 (range, 21-65 years). fitzpatrick skin types were i (5.7%, ii (40.9%) and iii (53.4%). • pre-treatment medication was limited to 800mg ibuprofen taken at least 60 minutes prior to treatment. • treatment groups are summarized in table 1. • assessments (baseline & follow-up visits): standardized photographs 5-point clinical erythema assessment (cea) scale colorimeter assessment • figures 1-3 illustrate the treatment maps used for each transducer depth and density. table 1. treatment groups. all subjects were to receive 2 treatments. group subjects, n treatments, n treatment density a 20 1 low (15 lines/square) b* 22 2 low (15 lines/square) c 24 1 high (30 lines/square) d* 22 2 high (30 lines/square) “*due to a treatment protocol modification, only subjects in groups b & d recieved 2 treatments (14 +/4 days apart). methods adverse event # subjects average duration of resolved aes (days)n=88 (%) bruising 39 44% 10.2 soreness/tenderness 38 43% 12.9 parasthesia (numbness) 9 10% 12.5 raised area of edema/welts 15 17% 9.0 erythema (redness) 33 35% 4.8 other (oily skin, worsening of rosacea, aphthous ulcer) 4 4.5% 2.0/31.0/10 figure 4. treatment success based on cea scores. cea improvement (≥1-grade improvement) was greatest in group c at day 90 (91%) and at day 365 (96%), group a at day 180 (95%). figure 5. treatment success based on psa scores. psa improvement (≥1-grade improvement) was greatest in group d at day 90 (74%), group d at day 180 (75%), and group b at day 365 (76%). figure 6. improved colorimeter readings. colorimeter improvement (reduction in red-green spectrum vs baseline only) was greatest in group a at day 90 (75%), group a at day 180 (74%), and group c at day 365 (86%). figure 7: mean pain scores, first treatment. mean pain scores were generally consistent between treatment groups; for subjects in group b &d, the second treatment pain scores were similar to the first treatment. table 1. adverse events. no serious adverse events were reported. results disclosure: this study and poster were sponsored by merz north america, inc. ultherapy® is a registered trademark of ulthera, inc. • results suggest ultherapy may be efficacious for treatment of signs and symptoms of erythematotelangiectatic rosacea. • study data suggest that high density ultherapy treatment is superior to low density treatments or to superficial treatments. conclusions figure 8. sample patient before (left) and at day 90 (right) % o f s ub je ct s w it h 1g ra d e im p ro ve m en t treatment group timepoint group a group b group c group d 0 10 20 30 40 50 60 70 80 90 100 day 90 (n=84) day 180 (n=84) day 365 (n=81)75 .0 % 91 .3 % 84 .2 %94 .7 % 94 .4 % 77 .3 % 85 .0 %95 .5 % 90 .9 % 85 .7 % 82 .6 % 80 .0 % % o f s ub je ct s sh ow in g im p ro ve m en t treatment group timepoint group a group b group c group d 0 10 20 30 40 50 60 70 80 90 100 day 90 (n=84) day 180 (n=84) day 365 (n=81) 60 .0 % 69 .6 % 73 .7 % 73 .7 % 66 .7 % 72 .7 % 60 .0 %7 2. 7% 72 .7 % 76 .2 % 65 .2 % 75 .0 % p ai n sc or e transducers treatment group 4-4.5mm 7-3.0mm 10-1.5mm 0 1 2 3 4 5 6 7 8 9 10 group a group b group c group d 6.5 6.7 6.4 3.9 4.9 5.9 5.55.6 3.9 4.6 4.4 4.4 % o f s ub je ct s sh ow in g im p ro ve m en t treatment group timepoint group a group b group c group d 0 10 20 30 40 50 60 70 80 90 100 75 .0 % 56 .5 % 72 .2 % 73 .7 % 72 .2 % 63 .6 % 8 0 .0 % 86 .4 % 68 .2 % 71 .4 % 69 .9 % 70 .0 % day 90 (n=84) day 180 (n=84) day 365 (n=81) figure 2. treatment map for 7 mhz/3.0 mm transducer. figure 3. treatment map for 10 mhz/1.5 mm transducer. figure 1. treatment map for 4 mhz/4.5 mm transducer. fc17postermerzgeorgeevaluationsafetyultherapy.pdf background validation of the severity of pruritus scale (sps) for the assessment of pruritus in atopic dermatitis (ad) gil yosipovitch,1 eric simpson,2 andrew g. bushmakin,3 joseph c. cappelleri,3 thomas luger,4 sonja ständer,4 wynnis tom,5 katy benjamin,6 william c. ports,3 anna m. tallman,7 huaming tan,3 robert a. gerber3 1university of miami, miller school of medicine, miami, fl, usa; 2oregon health and science university, portland, or, usa; 3pfizer inc., groton, ct, usa; 4university hospital münster, münster, germany; 5rady children’s hospital-san diego, san diego, ca, usa; 6icon plc, gaithersburg, md, usa; 7pfizer inc., new york, ny, usa presented at the 2017 fall clinical dermatology conference; october 12-15, 2017; las vegas, nv table 1. severity of pruritus scale instructions: please think about your itching (or your child’s itching if you are completing for your child) over the past 24 hours and choose the category that best describes it. score grade definition 0 none no itching 1 mild occasional, slight itching/scratching 2 moderate constant or intermittent itching/scratching which is not disturbing sleep 3 severe bothersome itching/scratching which is disturbing sleep objectives • to assess the content validity of the sps to ensure it is a clear and appropriate tool for the assessment of pruritus intensity • to evaluate the psychometric properties (quantitative validation) of the sps to ensure it is a valid and reliable measure of pruritus intensity methods qualitative content validation of the sps • a combined concept elicitation and cognitive interview study was conducted to evaluate the content validity of the sps in accordance with best practices6-10 • eligible participants were aged ≥2 years, had a dermatologist confirmed diagnosis of ad within the preceding 12 months, and had experienced itching caused by ad • participants completed a brief background questionnaire and took part in a single one-on-one interview – for children aged 2-7 years, the caregiver completed the sps and participated in the interview • because of the relative homogeneity of the us-only population and the single-item, single-concept nature of the sps, a target sample size of 15 subjects was considered adequate quantitative psychometric validation of the sps data set • data from the 2 identically designed, multicenter, randomized, double-blind, vehicle-controlled phase 3 clinical trials investigating the safety and efficacy of crisaborole were pooled to assess the psychometric properties of the sps (ad-301: nct02118766; ad-302: nct02118792) – 1522 patients aged ≥2 years with mild to moderate ad were included in the intent-to-treat population – efficacy was assessed using the investigator’s static global assessment (isga; a 5-point rating scale measuring overall disease severity from clear [0] to severe [4]); the sps; signs of ad (measured on a 4-point rating scale from none [0] to severe [3]); and health-related quality-of-life measures (dermatology life quality index [dlqi], children’s dermatology life quality index [cdlqi], dermatitis family impact questionnaire [dfi]) test-retest reliability • assessed via an intraclass correlation coefficient (icc) using all available sps observations from stable subjects between baseline/day 1 and day 8 (stable group was defined as having no change on isga between baseline/day 1 and day 8) – icc ≥0.70 was considered indicative of acceptable test-retest reliability; icc ≥0.90 was considered indicative of excellent test-retest reliability11,12 construct validity • convergent validity was evaluated by calculation of pearson correlations with the isga, quality-of-life instruments (dlqi, cdlqi, and dfi), and signs of ad – evidence for convergent validity was based on a pearson correlation ≥0.40 (correlations ≥0.50 were considered indicative of a strong association) • known-groups validity was assessed based on the difference in mean sps scores between the “no disease group/clear” (isga = 0) and the “severe disease group” (isga = 4) – sps scores as a function of isga were modeled using repeated-measures longitudinal analyses – the effect size was calculated as the difference in the mean divided by the baseline standard deviation (values of 0.20, 0.50, and 0.80 standard deviation units were considered small, medium, and large, respectively) ability to detect change • evaluated using a repeated-measures longitudinal mixed model to estimate the relationship between sps and isga scores clinically important difference • estimated using a repeated-measures longitudinal model linked to a 1-cateogry difference on the isga clinically important response • estimated using a repeated-measures longitudinal model with the change in sps score from baseline as the outcome and a newly created static global impression of change (sgic) anchor as the predictor (sgic was based on categorizing the change from baseline in isga scores as worse [–1], same [0], or better [1]) results qualitative content validation of the sps • 14 individuals participated in the content validation study (table 2) • 9 interviews were conducted in us english, and 5 were conducted in us spanish table 2. participant characteristics children 2-7 years of age n = 5 children 8-11 years of age n = 4 adolescents and adults n = 5 patients characteristics sex female 4 1 3 language english 3 3 3 age, mean (sd, range), years 5.0 (1.2, 3-6) 9.3 (1.5, 8-11) 27.8 (17.9, 17-59) race white black 4 1 2 2 5 0 ethnicity hispanic/latino 3 1 2 ad severity at interview (patient/caregiver reported) almost clear mild moderate severe 3 0 1 1 1 0 3 0 2 1 3 0 currently receiving ad treatment (any) 5 4 5 characteristics of caregivers of children 2-7 years of age (n = 5) sex female 4 — — language english 3 — — age, mean (sd, range), years 34.6 (4.5, 28-38) — — race white black 4 1 — — — — ethnicity hispanic/latino 3 — — working status homemaker full-time work part-time work 2 2 1 — — — — — — education level high school some college master’s degree 1 3 1 — — — — — — ad, atopic dermatitis; sd, standard deviation. concept elicitation • the most prevalent symptom was itch, with 79% (n = 11) of participants reporting it spontaneously and 21% (n = 3) reporting it after probing • other reported signs included change in skin color (50%, n = 7), dry skin (36%, n = 5), and change in skin texture (29%, n = 4) • concept saturation analysis showed that only 2 new concepts were reported by the fifth interview, and all concepts were reported by the ninth interview cognitive interview • all participants correctly interpreted the sps instructions and found them easy to understand (table 3) • most participants found the scale easy to complete and correctly interpreted the meaning of the questions and response options and the phrase “sleep disturbance” (table 3) table 3. summary of the cognitive interviewing results question results overview interpretation of sps instructions • 14 (100%) participants correctly interpreted the sps instructions easy or difficult to understand the instructions • 14 (100%) participants found the sps instructions easy to understand easy or difficult to complete the scale • 12 (86%) participants reported that the scale was easy to complete interpretation of item • 13 (93%) participants correctly interpreted the meaning of the question – 1 child (age 8 years) did not interpret the meaning of the question correctly interpretation of response options • 11 (79%) participants interpreted the response options consistently and in agreement with the provided definitions – 1 caregiver (us english) interpreted the meaning of each response option as frequency instead of severity – 1 child (age 8 years, us spanish) defined “moderate” as “night” – 1 child (age 8 years, us english) did not differentiate between “mild” and “moderate” meaning of “sleep disturbance” • 13 (93%) participants had no issues interpreting the terms “disturbing sleep” – 1 adult (us english) had difficulty interpreting the terms “disturbing sleep” recall period • 11 (79%) participants correctly interpreted the 24-hour recall period – 1 adult reported on itch “in general” – 1 adult thought about itch severity “a few weeks ago” – 1 child (age 11) interpreted the question as frequency during the past week rather than the past 24 hours how participant arrived at response • no issues were raised regarding how patients arrived at their answers sps, severity of pruritus scale. quantitative psychometric validation of the sps test-retest reliability • the icc value for a single sps measurement was estimated to be 0.54 • reliability improved with the use of multiple sps measurements – the average of 2 sps measurements (representing average pruritus over 1 day) provided an icc value of 0.70 (indicative of acceptable test-retest reliability) – the average of 14 sps measurements (representing average pruritus over a 1-week period) provided an icc value of 0.94 (indicative of excellent test-retest reliability) • ad is a chronic inflammatory skin disease characterized by the development of eczematous lesions1 • pruritus is a significant feature of ad and is believed to be responsible for much of the burden associated with the disease2 • crisaborole ointment is a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of mild to moderate ad3 • the safety and efficacy of crisaborole was established in 2 phase 3 clinical trials conducted in the united states (ad-301: nct02118766; ad-302: nct02118792)4 • pruritus was assessed within these trials using the sps, a 4-point rating scale, ranging from 0 (none: no itching) to 3 (severe, bothersome itching/scratching which disturbs sleep) that was adapted from the atopic dermatitis severity index5 to quantify pruritus intensity within a 24-hour period (table 1) construct validity • convergent validity was supported by strong correlation (pearson correlation ≥0.50) between sps scores and isga, dlqi, cdlqi, and dfi instruments, and correlations of ≥0.40 with 4 of 5 of the signs of ad at day 29 (table 4) table 4. correlation between the sps and all instruments (pearson correlation coefficient [r value]a) baseline day 8 day 15 day 22 day 29 isga 0.22 0.36 0.42 0.48 0.50 erythema (redness) 0.16 0.30 0.38 0.39 0.42 induration/ papulation 0.16 0.30 0.36 0.40 0.44 exudation (oozing or crusting) 0.18 0.29 0.29 0.36 0.35 excoriation (evidence of scratching) 0.25 0.36 0.42 0.45 0.41 lichenification (epidermal thickening) 0.16 0.31 0.33 0.35 0.40 dlqi 0.46 — — -— 0.59 cdlqi 0.47 — — — 0.58 dfi 0.38 — — — 0.53 cdlqi, children’s dermatology life quality index; dfi, dermatitis family impact questionnaire; dlqi, dermatology life quality index; isga, investigator’s static global assessment; sps, severity of pruritus scale. ap < 0.0001 for all correlations. • a 4-category difference in the isga (between the “no disease group/clear” and “severe disease group”) was associated with a difference in sps score of 0.80 (continuous anchor) and 0.87 (categorical anchor), indicating that the sps can distinguish between groups known to be different (table 5) table 5. known-groups validity of the sps in relation to scores on the isga data and model differences in mean sps scores on isga between the “severe disease group” and the “no disease group” difference (95% ci) es pooled studies (ad-301 and ad-302)a 0.80 (0.73-0.88) 1.03 pooled studies (ad-301 and ad-302)b 0.87 (0.73-1.0) 1.12 study ad-301a 0.75 (0.64-0.85) 0.96 study ad-301b 0.89 (0.71-1.07) 1.14 study ad-302a 0.86 (0.75-0.97) 1.10 study ad-302b 0.84 (0.65-1.04) 1.08 es, effect size; isga, investigator’s static global assessment; sps, severity of pruritus scale. es calculated as difference/standard deviation of 0.78 (based on pooled data from post hoc analyses). aisga as a continuous anchor. bisga as a categorical anchor. ability to detect change • the relationship between sps scores and isga scores provides evidence of sensitivity to change over time (table 6, figure 1) table 6. ability to detect change in the sps in relation to isga scores isga score mean sps score (95% ci) (isga continuous predictor) mean sps score (95% ci) (isga categorical predictor) pooled studies ad-301 and ad-302 0 0.79 (0.75-0.84) 0.84 (0.79-0.90) 1 0.99 (0.96-1.03) 0.99 (0.95-1.03) 2 1.19 (1.16-1.23) 1.16 (1.13-1.20) 3 1.40 (1.36-1.44) 1.42 (1.38-1.47) 4 1.60 (1.54-1.65) 1.71 (1.59-1.83) study ad-301 0 0.82 (0.75-0.89) 0.88 (0.80-0.96) 1 1.01 (0.95-1.06) 0.99 (0.94-1.05) 2 1.19 (1.14-1.24) 1.17 (1.11-1.22) 3 1.38 (1.32-1.44) 1.40 (1.34-1.47) 4 1.57 (1.49-1.64) 1.76 (1.59-1.93) study ad-302 0 0.77 (0.70-0.83) 0.81 (0.72-0.89) 1 0.98 (0.93-1.03) 0.98 (0.92-1.04) 2 1.20 (1.15-1.24) 1.16 (1.11-1.21) 3 1.41 (1.36-1.47) 1.44 (1.39-1.50) 4 1.63 (1.55-1.70) 1.65 (1.47-1.83) isga, investigator’s static global assessment; sps, severity of pruritus scale. clinically important difference • the estimated clinically important difference for sps was 0.20 (95% ci, 0.18-0.22) – the close functional relationship when using the isga as a categorical variable and continuous predictor supports the linearity assumption of the relationship between isga and sps scores (figure 1) figure 1. sps score as a function of the isga as a continuous anchor and a categorical anchor. 0.50 0.75 1.00 1.25 1.50 2.00 0 1 2 3 4 isga m e a n s p s s c o r e 1.75 sps score (isga as a continuous anchor) sps score (isga as a categorical anchor) isga, investigator’s static global assessment; sps, severity of pruritus scale. clinically important response • a 1-category difference in sgic corresponded to 0.19 points (95% ci, 0.16-0.22) in sps score – using the anchor as a categorical variable provided a close functional relationship to the results using the anchor as a continuous predictor, supporting the linearity assumption for the relationship between change from baseline of the sps score and sgic score (figure 2) • the responder definition was estimated as a decrease of 0.19 points from baseline in sps score, linked to a 1-category difference between the sgic categories figure 2. sps change score as a function of the sgic as a continuous anchor and a categorical anchor predictor. –1.0 –0.9 –0.8 –0.5 –1 0 1 sgic m e a n c h a n g e f r o m b a s e li n e i n s p s s c o r e –0.7 –0.6 change from baseline in sps score (sgic as a continuous anchor) change from baseline in sps score (sgic as a categorical anchor) sgic, static global impression of change; sps, severity of pruritus scale. conclusions • the results of the qualitative content validation analysis confirm that itch is a significant symptom of ad and that the sps is easy to understand and to complete in both us english and us spanish • the results of the quantitative analysis confirm the validity of the sps, demonstrating that it has acceptable test-retest reliability provided ≥2 sps measurements are used, has good convergent and known-group validity, and has an ability to adequately detect change • a clinically important difference and a clinically important response were also identified, which could be used in future investigations that use the sps to assess pruritus severity references 1. weidinger s, novak n. lancet. 2016;387(10023):1109-1122. 2. eichenfield lf et al. j am acad dermatol. 2014;70(2):338-351. 3. eucrisa (crisaborole) ointment, 2%, for topical use [prescribing information]. palo alto, ca: anacor pharmaceuticals, inc.; 2016. 4. paller as et al. j am acad dermatol. 2016;75(3):494-503.e6. 5. van leent ej et al. arch dermatol. 1998;134(7):805-809. 6. us department of health and human services. guidance for industry patient-reported outcome measures: use in medical product development to support labeling claims. december 2009. https://www.fda.gov/downloads/drugs/guidances/ ucm193282.pdf. accessed september 20, 2017. 7. patrick dl et al. value health. 2011;14(8):978-988. 8. patrick dl et al. value health. 2011;14(8):967-977. 9. brod m et al. qual life res. 2009;18(9):1263-1278. 10. lasch ke et al. qual life res. 2010;19(8):1087-1096. 11. nunnally jc, bernstein ih. psychometric theory. 3rd ed. new york: mcgraw-hill; 1994. 12. reeve bb et al. qual life res. 2013;22(8):1889-1905. acknowledgments editorial/medical writing support under the guidance of the authors was provided by jemimah walker, phd, and corey mandel, phd, at apothecom, san francisco, ca, usa, and was funded by pfizer inc., new york, ny, usa, in accordance with good publication practice (gpp3) guidelines (ann intern med. 2015;163:461-464). fc17posterpfizeryosipovitchvalidation.pdf a randomized, double-blind, multicenter study to compare the efficacy, safety, and immunogenicity of a proposed adalimumab biosimilar (gp2017) with originator adalimumab in patients with moderate-to-severe chronic plaque psoriasis andrew blauvelt,1 joseph f fowler jr,2 ellen schuck,3 julia jauch,3 heike woehling,3 and craig l leonardi4 1oregon medical research center, portland, oregon; 2dermatology specialists, louisville, kentucky; 3hexal ag, holzkirchen, germany; 4central dermatology, st louis, missouri introduction • gp2017 is being developed as a proposed biosimilar to originator adalimumab. – extensive state-of-the-art analytical studies have shown that gp2017 and originator adalimumab have identical amino acid sequences, indistinguishable secondary and tertiary structures, the same level of post-translational modifications, and similar in vitro functionality.1 – pharmacokinetic (pk) bioequivalence was demonstrated in phase i pk studies in healthy volunteers, with gp2017 and originator adalimumab having similar clinical safety and immunogenicity profiles. • the purpose of this phase iii confirmatory study (nct02016105) was to show equivalent efficacy and comparable safety and immunogenicity between gp2017 and originator adalimumab up to 51 weeks in patients with moderate-to-severe chronic plaque psoriasis. – here, data from randomization to week 17 are presented for patients receiving gp2017 or originator adalimumab. study design • this was a multicenter, randomized, double-blinded, comparator-controlled phase iii confirmatory study with four study periods (figure 1). gp2017 gp2017 gp2017 gp2017 gp2017 originator adalimumab originator adalimumab day 1 randomization screening treatment period 1 treatment period 2 extension period end of study week 16 analysis of primary endpoint week 17 re-randomization week 23 week 29 week 35 sw itched groups w 17 – w 51 c ontinued groups random ization to w 51 week 51 gp2017 gp2017 { originator adalimumab originator adalimumab originator adalimumab originator adalimumab originator adalimumab figure 1. study design • adult male and female patients with active, but clinically stable, moderate-to-severe chronic plaque psoriasis were eligible for enrolment if they were ≥18 years of age; had a baseline pasi score of ≥12, an investigators global assessment (iga) score of ≥3, and a body surface area (bsa) affected by plaque psoriasis of ≥10%; had previously received phototherapy or systemic psoriasis therapy or were candidates for such therapies; had no history of active or latent hepatitis b and/or c infections or tuberculosis, and had not received prior treatment with adalimumab. • in treatment period 1, patients were randomized to receive an initial dose of 80 mg subcutaneous gp2017 or originator adalimumab sourced from either the eu or us, followed by 40 mg every other week, starting one week after the initial dose, up to week 17. primary endpoint • proportion of patients who achieved a 75% improvement in the psoriasis area and severity index score (pasi 75) at week 16. – therapeutic equivalence was confirmed if the 95% confidence interval (ci) for the difference in pasi 75 response rates between gp2017 and originator adalimumab for the per-protocol set (pps) was contained within a margin range of ±18%. secondary endpoints • percentage change from baseline until week 16 in the continuous pasi score, with equivalence concluded if the 95% ci was within ±15% • pasi 50, pasi 90 and pasi 100 response rates over time • percentage change from baseline in pasi score at each visit • iga response rate: proportion of patients with a score of 0 (clear) or 1 (almost clear) on the iga scale (0–4) and ≥2 point improvement from baseline • health-related quality of life (hrqol) with regard to relative changes in the dermatology life quality index (dlqi) and euroqol 5-dimension health (eq-5d) status questionnaire from baseline to weeks 11, 16, and 17 • safety, immunogenicity, tolerability and local tolerance results patients • the full analysis set (fas) comprised 231 patients who received gp2017 and 234 patients who received originator adalimumab. – of these, 197 and 196 patients completed the study up to week 16 with no major protocol deviations and were included in the pps. • patient demographics and disease characteristics were balanced across both treatment groups (table 1). table 1. baseline patient and disease characteristics (fas) gp2017 (n=231) originator adalimumab (n=234) age (years), mean (sd) 45.6 (14.2) 46.9 (14.1) male, n (%) 142 (61.5) 142 (60.7) race, n (%) caucasian 196 (84.8) 201 (85.9) black 14 (6.1) 9 (3.8) asian 3 (1.3) 5 (2.1) other 18 (7.8) 19 (8.1) bmi (kg/m2), mean (sd) 31.4 (8.1) 30.7 (7.5) duration since diagnosis (years), mean (sd) 15.3 (12.6) 16.9 (14.7) pasi score, mean (sd) 19.9 (8.6) 20.2 (7.7) iga score, n (%) 3=moderate 152 (65.8) 154 (65.8) 4=severe 79 (34.2) 80 (34.2) % bsa affected, mean (sd) 28.9 (17.1) 29.7 (15.6) presence of psoriatic arthritis, n (%) 52 (22.5) 46 (19.7) prior systemic psoriasis therapy, n (%) biologic 54 (23.4) 44 (18.8) nonbiologic 72 (31.2) 81 (34.6) bmi, body mass index; bsa, body surface area; iga, investigator’s global assessment; pasi, psoriasis area and severity index; sd, standard deviation efficacy • in the pps, the pasi 75 response rate difference at week 16 was 1.8% (66.8% for gp2017 and 65.0% for originator adalimumab). – as the 95% ci was contained within the prespecified margin range of ±18%, equivalent efficacy between gp2017 and originator adalimumab was confirmed (figure 2a). • using a mixed model repeated measures method, mean percent change (improvement) from baseline up to week 16 in pasi score was 60.7% for gp2017 and 61.5% with originator adalimumab in the pps. – the 95% ci for the difference in the percentage change from baseline in pasi up to week 16 was contained within ±15%; thereby showing therapeutic equivalence (figure 2b). pa tie nt s w ith p a si 7 5 re sp on se a t w ee k 16 , % m ea n pe rc en t c ha ng e in p a si fro m b as el in e to w ee k 16 1.8% (95% ci: –7.46% to 11.15%) a b –0.8% (95% ci: –3.15% to 4.84%) 100 90 80 70 60 50 40 30 20 10 0 gp2017 originator adalimumab gp2017 originator adalimumab 66.8 65 0 –10 –20 –30 –40 –50 –60 –70 –80 –90 –100 –60.7 –61.5 figure 2. primary and key secondary efficacy analyses (pps) • pasi response rates for gp2017 and originator adalimumab were similar over time (figure 3). % r es po ns de rs week pasi 50 gp2017 (n=197) originator adalimumab (n=196) pasi 75 pasi 90 pasi 100 100 90 80 70 60 50 40 30 20 10 0 1 3 5 7 9 11 13 15 16 17 figure 3. pasi response rates over time (pps) • mean percent changes in pasi score from baseline were similar (figure 4) % c ha ng e fro m b as el in e in p a si s co re week gp2017 (n=197) originator adalimumab (n=196) 10 0 –10 –20 –30 –40 –50 –60 –70 –80 –90 –100 1baseline 3 5 7 9 11 13 15 16 17 figure 4. mean percent change from baseline in pasi score (pps) • iga response rates increased over time and were similar in both treatment groups (figure 5). % r es po nd er s week gp2017 (n=197) originator adalimumab (n=196) 70 60 50 40 30 20 10 0 1 3 5 7 9 11 13 15 16 17 figure 5. iga response rates over time (pps) hrqol • the proportion of patients in the pps reporting a dlqi of 0 or 1 (no effect at all on patient’s life) was similar between the treatment groups at all time points (table 2). • mean eq visual analog scale scores, which range from 0 to 100 with lower scores indicating greater impairment in hrqol, were also similar (table 2). table 2. improvements in hrqol (pps) dlqi score of 0 or 1, n/n (%) eq visual analog scale score (sd) gp2017 originator adalimumab gp2017 originator adalimumab baseline 4/197 (2.0) 8/195 (4.1) 69.9 (22.1) 70.0 (23.2) week 11 79/194 (40.7) 79/193 (40.9) 77.5 (18.8) 78.2 (20.1) week 16 98/191 (51.3) 88/191 (46.1) 80.6 (17.0) 80.2 (20.0) week 17 97/192 (50.5) 93/192 (48.4) 80.5 (17.1) 80.7 (19.7) safety • among all patients who received ≥1 dose of study drug (safety analysis set; saf), adverse events (aes) occurred in 50.2% and 52.6% of patients treated with gp2017 and originator adalimumab, respectively; most of which were mild or moderate in severity (table 3). • the proportions of patients with severe aes, serious aes (saes), treatmentrelated saes, aes of special interest, aes requiring study drug interruption, and discontinuations due to aes were low across both treatment groups. table 3. incidence of aes from randomization to week 17 (saf) patients, n (%) gp2017 (n=231) originator adalimumab (n=234) ≥1 ae 116 (50.2) 123 (52.6) ≥1 severe ae 3 (1.3) 10 (4.3) ≥1 sae 3 (1.3) 10 (4.3) ≥1 treatment-related ae 33 (14.3) 28 (12.0) ≥1 treatment-related sae 1 (0.4) 3 (1.3) ae of special interest 13 (5.6) 17 (7.3) treatment interruption due to ae 5 (2.2) 4 (1.7) discontinuation due to ae 4 (1.7) 7 (3.0) died 0 (0.0) 0 (0.0) • infections/infestations were most common, with nasopharyngitis most frequently reported (table 4). table 4. aes by system organ class and preferred term (≥2% in any treatment group) from randomization to week 17 (saf) system organ class preferred term patients, n (%) gp2017 (n=231) originator adalimumab (n=234) infections and infestations 55 (23.8) 56 (23.9) nasopharyngitis 13 (5.6) 15 (6.4) upper respiratory tract infection 11 (4.8) 9 (3.8) sinusitis 8 (3.5) 7 (3.0) general disorders and administration site conditions 23 (10.0) 15 (6.4) injection site erythema 9 (3.9) 3 (1.3) fatigue 5 (2.2) 6 (2.6) musculoskeletal and connective tissue disorders 22 (9.5) 15 (6.4) back pain 6 (2.6) 3 (1.3) arthralgia 6 (2.6) 2 (0.9) nervous system disorders 19 (8.2) 14 (6.0) headache 11 (4.8) 8 (3.4) respiratory, thoracic and mediastinal disorders 15 (6.5) 15 (6.4) gastrointestinal disorders 14 (6.1) 27 (11.5) diarrhea 2 (0.9) 9 (3.8) skin and subcutaneous tissue disorders 12 (5.2) 15 (6.4) injury, poisoning and procedural complications 9 (3.9) 8 (3.4) investigations 8 (3.5) 9 (3.8) psychiatric disorders 6 (2.6) 5 (2.1) metabolism and nutrition disorders 5 (2.2) 7 (3.0) neoplasms benign, malignant and unspecified 4 (1.7) 5 (2.1) blood and lymphatic system disorders 3 (1.3) 5 (2.1) vascular disorders 2 (0.9) 7 (3.0) reproductive system and breast disorders 2 (0.9) 5 (2.1) immunogenicity • 36.8% patients treated with gp2017 and 34.1% of patients treated with originator adalimumab were anti-drug antibody (ada)-positive at least once up to week 17. • approximately 80% of ada were neutralizing. conclusions • week 17 results of this phase iii confirmatory study show equivalent efficacy of gp2017 and originator adalimumab. • safety and immunogenicity profiles of gp2017 and originator adalimumab were also similar and consistent with clinical experience with originator adalimumab. reference 1. schiestl m, roesli c. am j gastroenterol 2016; 111:s260–s335 disclosure statement nct02016105 is sponsored by sandoz. es, jj, and hw are paid employees of hexal ag. cl has served as a consultant for abbvie, amgen, boehringer ingelheim, dermira, janssen, eli-lilly, leo, sandoz, ucb, pfizer and vitae and is a member of the speaker bureau for abbvie, celgene, novartis and eli lilly. medical writing support was provided by spirit medical communications, funded by sandoz. fc17postersandozblauvelt.pdf abametapir lotion, 0.74%, a novel therapy for the treatment of head lice, pooled safety results from 11 trials, in children as young as 6 months lydie hazan, md1; david cardona, md2; sharon hanegraaf3; tiina ahveninen3; hugh alsop3; vernon m bowles, phd4; 1axis clinical trials, los angeles, ca; 2universal biopharma research institute inc., dinuba, ca; 3hatchtech, melbourne, australia; 4university of melbourne, melbourne, australia; results introduction abametapir lotion, 0.74% is being developed for the single application treatment of head lice infestation. the active ingredient is a novel compound, abametapir. abametapir lotion, 0.74% has been tested in 11 clinical trials, including 6 trials with pediatric subjects. objectives ¾ to evaluate the clinical safety results in children as young as 6 months following exposure to abametapir lotion 0.74%. ¾ a total of 1372 subjects were evaluated in 11 clinical studies of abametapir lotion, 0.74% including 6 studies with a total of 676 pediatric subjects (aged 6 months to 17 years). methods ¾ these 6 trials included one phase 2b trial, one phase 2 ovicidal efficacy trial, two openlabel phase 2 pk trials of maximal use, and two phase 3 vehicle-controlled trials. ¾ across all trials, subjects ranged in age from 6 months to 60 years and exposure times ranged from 10 minutes to 20 minutes. ¾ of the 905 subjects exposed to study treatment for 10 minutes, 483 received abametapir lotion, 0.74% and 422 received vehicle lotion. ¾ safety assessments included vital signs, physical examination, clinical laboratory tests, and adverse events (aes). ¾ the most frequently reported treatment-emergent aes for pediatric subjects were in the system organ class of skin and subcutaneous tissue disorders, primarily erythema, rash, skin burning sensation, and contact dermatitis. ¾ teaes were similar for adult and pediatric subjects. ¾ the majority of aes were mild and there was no evidence of an age-related effect. ¾ the two maximal-use pediatric trials had study drug exposure ranging from 3.3 g to 200.8 g, and reported 14 aes (23.3%) (table 1). ¾ in the two phase 3 trials, aes were reported by 24.4% subjects using abametapir lotion, 0.74% and 18.6% subjects using vehicle (table 2). one serious ae, unrelated to study treatment, was reported in the vehicle group. ¾ there were no deaths, no discontinuations due to aes and no clinically meaningful changes in vital signs, physical exams or laboratory tests in any of these trials. conclusions ¾ in 11 clinical studies of abametapir lotion, 0.74% for the treatment of head lice in subjects ranging in age from 6 months to 60 years, aes were mild, not age-related, and primarily in the system organ class of skin and subcutaneous tissue disorders. financial support: this study was funded and supported by hatchtech pty ltd, melbourne, australia. drl publication #796 table 2. summary of aes in the soc of skin and subcutaneous tissue disorders reported in two phase 3 trials and one phase 2 ovicidal efficacy trial table 1.summary of adverse events in the soc of skin and subcutaneous tissue disorders in phase 2 pk trials soc preferred term study ha02-003 study ha03-003 study ha03-004 aba 0.74% n = 49 vehicle n = 47 aba 0.74% n = 22 aba 0.74% n = 38 overall incidence 13 (26.5) 27 (57.4) 6 (27.3) 8 (21.1) skin & subcutaneous tissue disorders 7 (14.3) 19 (40.4) 4 (18.2) 5 (13.2) pruritus 2 (4.1) 18 (38.3) 1 (4.5) 0 erythema 0 2 (4.3) 0 0 dermatitis 0 0 1 (4.5) 0 dermatitis contact 3 (6.1) 0 0 2 (5.3) dermatitis allergic 2 (4.1) 0 0 0 rash 0 0 1 (4.5) 0 exfoliative rash 1 (2.0) 0 0 0 dry skin 0 1 (2.1) 0 0 rash macular 0 0 0 1 (2.6) rash popular 0 0 0 1 (2.6) skin disorder 0 0 1 (4.5) 0 skin irritation 0 0 0 1 (2.6) soc preferred term ha03-001 ha03-002 ha03-008 aba 0.74% n = 186 n (%) vehicle n = 188 n (%) aba 0.74% n = 163 n (%) vehicle n = 162 n (%) aba 0.74% n = 25 n (%) vehicle n = 25 n (%) overall incidence 37 (19.9) 32 (17.0) 48 (29.4) 33 (20.4) 6 (24.0) 4 (16.0) skin & subcutaneous tissue disorders 16 (8.6) 14 (7.4) 32 (19.6) 23 (14.2) 5 (20.0) 3 (12.0) erythema 4 (2.2) 0 10 (6.1%) 6 (3.7) 0 1 (4.0) skin exfoliation 1 (0.5) 0 2 (1.2) 8 (4.9) 0 0 skin burning sensation 0 0 9 (5.5) 0 0 0 rash 2 (1.1) 0 7 (4.3) 8 (4.9) 4 (16.0) 2 (8.0) pruritus 1 (0.5) 8 (4.3) 2 (1.2) 2 (1.2) 1 (4.0) 0 dermatitis 0 0 0 3 (1.9) 0 0 dry skin 0 0 0 3 (1.9) 0 0 hair color changes 0 0 3 (1.8) 0 0 0 urticaria 0 0 0 2 (1.2) 0 0 rash pruritic 0 0 0 1 (0.6) 0 0 skin plaque 0 1 (0.5) 0 1 (0.6) 0 0 swelling face 0 0 0 1 (0.6) 0 0 dermatitis contact 6 (3.2) 4 (2.1) 0 0 0 0 rash erythematous 0 1 (0.5) 0 0 0 0 skin disorder 2 (1.1) 0 0 0 0 0 skin irritation 2 (1.1) 0 0 0 0 0 note: aba 0.74% = abametapir lotion, 0.74% note: aba 0.74% = abametapir lotion, 0.74% fc17posterpromiushazanabametapirlotionsafety6months.pdf a randomized vehicle-controlled trial to assess the efficacy, safety and tolerability of ozenoxacin 1% cream in 412 patients 2 months and older with impetigo n. albareda1, j. zeichner2, n. rosenberg3 1 ferrer, barcelona, spain; 2 mount sinai school of medicine, nyc; 3 medimetriks, fairfield, nj this poster and study was funded by medimetriks pharmaceuticals, inc. and ferrer internacional sa pp1539-r1 resultsabstract conclusion methods introduction ozenoxacin is a non-fluorinated quinolone antibiotic with potent activity against grampositive bacteria that is being developed as a 1% cream for the topical treatment of impetigo. objectives the objectives of this study were to compare the efficacy and evaluate the safety and tolerability of ozenoxacin 1% cream versus vehicle after 5 day bid topical applications (10 applications) in patients with impetigo. methods a phase 3 multicenter, randomized, vehicle-controlled, parallel, double-blind clinical trial in patients aged 2 months and older with impetigo. patients were randomized in a 1:1 ratio to ozenoxacin or vehicle. efficacy was evaluated utilizing a clinical skin infection rating scale (sirs) and by microbiological culture. safety and tolerability were also evaluated. results after 5 days of treatment, ozenoxacin demonstrated clinical superiority to vehicle in clinical response, both for the primary endpoint as well as for the prespecified secondary endpoint of combined criteria of clinical success. ozenoxacin also demonstrated superior microbiological success compared to vehicle as early as after 2 days of treatment. ozenoxacin was safe and well tolerated, and these results are consistent with previously published phase 3 results (gropper 2014). conclusions ozenoxacin demonstrated superior clinical and microbiological response versus vehicle, and was safe and well tolerated. ozenoxacin represents a novel topical therapeutic option being developed for the treatment of impetigo. • a total of 412 patients were enrolled into the study globally at 11 sites in the usa, 5 in puerto rico, 4 sites in germany, 4 sites in romania, 6 sites in russia, 3 sites in south africa and 1 site in spain. • eligible patients were randomized to receive ozenoxacin 1% cream (203 patients) or vehicle (199 patients) applied topically bid for 5 days to all impetigo affected areas, with a maximum extension of 100 cm2. the first application was done under the guidance of the delegated person appointed by the investigator. after randomization, patients returned at: visit 2 (day 3-4) and visit 3 (day 6-7). patients returned for a final visit (visit 4, day 10-13). additionally, a telephone contact on day 2 (24-36 hours after baseline visit) was required to assess for any worsening of infection. • the primary efficacy endpoint was clinical response (success or failure) at end of therapy (visit 3) analyzed in the intent-to-treat clinical (ittc) population. • success at visit 3 was defined as a sirs score of 0 for blistering, exudates/pus, crusting, itching/pain and no more than 1 for erythema/inflammation, tissue edema and itching. it was also required that no additional anti-microbial therapy on the baseline affected area(s) was necessary. • main secondary efficacy endpoints were clinical response at all visits in all study populations and microbiological response (success or failure) at all visits in the bacteriological population. • the evaluation of safety was based on the assessment of adverse events (type, nature, incidence and outcome) and changes in vital signs and physical examination. • for all efficacy analyses, the primary treatment comparison of interest was ozenoxacin versus vehicle in order to test the superiority of ozenoxacin versus vehicle. in summary, in a randomized controlled trial of 412 patients that included adults and children ages 2 months and older with impetigo, ozenoxacin demonstrated superior clinical and microbiological response versus vehicle after 5 days of therapy, and was safe and well tolerated. ozenoxacin represents a novel topical therapeutic option being developed for the treatment of impetigo. table 1. primary endpoint clinical response at end of therapy (visit 3, day 6-7) (ittc population) p881 ozenoxacin vehicle n 203 199 clinical success 112 (55.2%) 78 (39.2%) clinical failure 91 (44.8%) 121 (60.8%) difference in success rates 0.160 p-value 0.001 ozenoxacin showed a statistically significant superior clinical response compared to vehicle at end of treatment. table 2. combined criteria of clinical success at end of therapy (visit 3, day 6-7) (ittc population) p881 ozenoxacin vehicle n 203 202 clinical success 183 (90.1%) 161 (79.7%) clinical failure 20 (9.9%) 41 (20.3%) difference in success rates 0.104 p-value 0.003 the prespecified secondary endpoint of combined criteria of clinical success was defined as a total absence of the treated lesions (lesion extension=0) or the treated lesions became dry without crusts compared to baseline (sirs=0 for exudate and for crusting), or improvement (defined as decline in the size of the affected area, number of lesions or both) such that no further antimicrobial therapy was necessary. this broader definition of clinical success includes improvement, and reflects the same criteria for clinical success as that used in pivotal phase 3 clinical trials of other topical antibiotics approved for impetigo. overall, 3.9% in the ozenoxacin group experienced at least 1 treatment-emergent adverse event (teae), and 3.6% in the vehicle group. no severe teaes were reported. the incidence of study drug related teaes was comparable in the treatment groups, with each group having 2 related teaes. no patients experienced an serious adverse event (sae) during the study. four patients (1%) had teaes leading to discontinuation of study drug or early discontinuation from the study due to the event: 3 patients were in the placebo group and 1 in the ozenoxacin group. table 3. microbiological response at visit 2 (day 3-4) and at end of therapy (visit 3, day 6-7) (ittb population) p881 ozenoxacin vehicle visit 2, day 3-4 n 125 108 microbiological success 109 (87.2%) 76 (70.4%) microbiological failure 16 (12.8%) 32 (29.6%) difference in success rates 0.168 p-value 0.002 visit 3, day 6-7 n 123 107 microbiological success 115 (93.5%) 87 (81.3%) microbiological failure 8 (6.5%) 20 (18.7%) difference in success rates 0.122 p-value 0.005 ozenoxacin demonstrated a statistically significant superior microbiological response compared to vehicle at visit 2 (day 3-4) and at end of treatment visit 3 (day 6-7). fc17postermedimetriksalbaredarandomized412patients.pdf epq domain: activities of daily living richard g. fried,1 evan a rieder,2 andrew f. alexis,3 hilary baldwin,4 emmy graber,5 julie c. harper,6 linda stein gold,7 adelaide hebert,8 james del rosso,9 leon kircik,10 ayman grada,11 siva narayanan,12 volker koscielny,13 ismail kasujee13 1yardley dermatology associates, morrisville, pa; 2new york university grossman school of medicine, new york, ny; 3the dermatology institute of boston and northeastern university, boston, ma; 4acne treatment and research center, brooklyn, ny; 5grada dermatology research llc, chesterbrook, pa; 6the dermatology and skin care center of birmingham, birmingham, al; 7weill cornell medical college, new york, ny; 8henry ford health system, bloomfield, mi; 9uthealth mcgovern medical school, houston, tx; 10jdr dermatology research/thomas dermatology, las vegas, nv; 11icahn school of medicine, mount sinai, new york, ny; 12almirall sa, barcelona, spain; 13avant health llc, bethesda, md. presented at fall clinical dermatology conference, 2022 – october 19-23, 2022 – las vegas, nv • acne vulgaris, hereinafter referred to as acne, affects up to 50 million americans and is the most common skin condition in the united states (us). 1 • acne has been shown to negatively affect qol; resulting in low selfesteem and increased social and emotional anxiety. 2,3 • patients with acne report more effects of their skin condition on their functioning, emotions, and symptoms than do patients with isolated benign skin lesions or those in the normative sample. 4 • acne has been associated with considerable psychosocial impact, causing significant negative effects on self-image, leading to feelings of isolation and loneliness, and a significantly lower self-attitude, uselessness feeling, sense of pride and self-worth, and body satisfaction. 5 • sarecycline is a newer oral tetracycline-derived, narrow spectrum antibiotic, a first line therapy treatment for moderate to severe acne patients. sarecycline is a viable option for acne patients to reduce disease burden, due to its safety profile and efficacy demonstrated in two identical phase-iii randomized controlled trials. 6 • assessing pros among patients in real-world setting is important to inform hcps and patients to aid optimal disease management. background 1. bickers dr, lim hw, margolis d, et al. j am acad dermatol. 2006; 55:490-500. 2. timms rm. psychol health med. 2013; 18(3):310–320. 3. revol o, milliez n, gerard d. br j dermatol. 2015; 172(suppl 1):52–58. 4. lasek rj, chren mm. arch dermatol. 1998; 134: 454-8. 5. gieler u et al. jeadv. 2015; 29 (suppl. 4):12–14. 6. moore a, green lj, bruce s, et al. j drugs dermatol. 2018 sep 1;17(9):987-996. 7. seite s et al. clin cosmet investig dermatol. 2012; 5:123–128. 8. lafrance, m., carey, r. s. body & society. 2018; 24(1-2), 55-87. sponsored by almirall, s.a. references conclusions • acne related burden was pronounced at baseline. • over the 12-week study period, patients reporting no/least acne burden increased significantly, while those reporting most/highest burden decreased significantly in emotional functioning, social functioning, and adl domains among patients with moderate to severe acne who were administered sarecycline for 12 weeks. methods • single-arm, prospective cohort study (proses) was conducted with moderate to severe non-nodular acne patients >9 years who were prescribed sarecycline in real-world community practices in the us. • a total of 300 subjects were enrolled from 30 community practices across the u.s. • study primary outcome measures included responses to epq items (completed by subjects (>12 years) and caregivers (for subjects 9-11 years) at week-12 and corresponding change from baseline (cfb)). • a 10-person consensus panel of eight dermatologists with expertise in the treatment of acne, one dermatologist/clinical psychologist and one dermatologist/psychiatrist was virtually convened using a three-step modified delphi method to establish consensus on 11-item epq that relate to how acne impacts the patient’s mood, social interactions, general thoughts/worries about acne and one’s future goals, and impact on daily activities, including sleep. these recommendations were aligned with literature depicting the issues impacting acne patients.7,8 • epq consisted of three domains: emotional functioning (epq items 1-4), social functioning (epq items 5-7), and adl (epq items 8-11). • all epq items were scored on a five-point adjectival response scale (0: never, not at all; 1: slightly, rarely, a little; 2: some of the time, somewhat, 3: most of the time, moderately, quite a bit; 4: all of the time, extremely, very much). • cfb in epq items was analyzed by evaluating the change in proportion of patients reporting score=0/1 (no/least impact) for epq items at week-12, in comparison to baseline. objective • to evaluate patient-perceived impact of av on emotional functioning, social functioning and activities of daily living (adl), using a novel expert panel questionnaire (epq), among acne patients administered sarecycline in real-world community practices across the u.s. patient’s emotional and physical functioning and adl significantly improved over the 12-week sarecycline treatment period in comparison to baseline: *p<0.0001; ^p<0.0001; **p=0.0009; ^^p=0.0005; #p=0.0042. n=253 for all items, except for epq10 which corresponded to only caregivers of pediatric patients, with n=101. epq domain: social functioning results • 253 patients with data at week-12 were included in the final analyses. cfb in proportion of patients reporting (never/rarely, not at all/slightly/a little) for epq items significantly improved over the 12-week sarecycline treatment period epq cfb p-value epq1 31.6% p<0.0001 epq2 28.9% p<0.0001 epq3 20.9% p<0.0001 epq4 38.7% p<0.0001 epq5 23.7% p<0.0001 epq6 22.9% p<0.0001 epq7 21.3% p<0.0001 epq8 15.0% p=0.0001 epq9 13.8% p=0.0005 epq10 1.0% p=0.8491 epq11 18.2% p<0.0001 results patient demographics (n=253) demographic group proportion of patients age group pediatric (<18 yrs) 39.9% adult (>18 yrs) 60.1% gender male 33.6% female 66.4% race white 68.4% other 15.4% black/african american 9.9% asian 7.1% prefer not to answer 3.2% native hawaiian/pacific islander 1.2% american indian /alaskan 0.8% • proportion of patients reporting no/least acne burden (i.e., epq item scores of 0/1: (never/rarely; not at all/slightly) statistically significantly (p<0.001) increased at week-12 across all measures, except epq10. • proportion of patients reporting high acne burden (i.e., epq item scores of 3/4: most of the time/all of the time) statistically significantly (p<0.001) decreased at week-12 across all measures, except epq10. impact of acne on social functioning, emotional functioning, and activities of daily living among patients with moderate to severe non-nodular acne vulgaris administered sarecycline in real-world community practices across the u.s. (proses study) 43.9% 35.2% 21.0% 75.5%* 16.6% 7.9%^ 0.0% 100.0% never/rarely some of the time most /all of the time p ro po rti on o f p at ie nt s baseline 12 weeks epq1: over the past 7 days, how often has your acne made you feel angry (mad/sad)? 20.6% 22.9% 56.5% 49.4%* 22.1% 28.5%^ 0.0% 100.0% not at all/ slightly somewhat moderately/ extremely p ro po rti on o f p at ie nt s baseline 12 weeks epq2: how worried are you about how long your acne will last and how bad it will get? 15.8% 34.8% 49.4% 36.8%* 41.9% 21.3%^ 0.0% 100.0% never/ rarely some of the time most/ all of the time p ro po rti on o f p at ie nt s baseline 12 weeks epq3: how often do you think about your acne? 27.3% 26.1% 46.6% 66.0%* 22.1% 11.9%^ 0.0% 100.0% not at all/ slightly somewhat moderately/ extremely p ro po rti on o f p at ie nt s baseline 12 weeks epq4: over the past 7 days, how worried have you been about your acne? 48.6% 18.6% 32.8% 72.3%* 15.0% 12.7%^ 0.0% 100.0% never/ rarely some of the time most/ all of the time p ro po rti on o f p at ie nt s baseline 12 weeks epq5: how often do you change, edit, or filter your social media photo or selfie because of your acne? 55.3% 26.1% 18.6% 78.3%* 15.8% 5.9%^ 0.0% 100.0% never/ rarely some of the time most / all of the time p ro po rti on o f p at ie nt s baseline 12 weeks epq6: how often does acne impact your “in real life” plans? 27.3% 24.5% 48.2%48.6%* 21.0% 30.4%^ 0.0% 100.0% never/rarely some of the time most/all of the time p ro po rti on o f p at ie nt s baseline 12 weeks epq7: how often are you doing something to hide your acne? 73.1% 16.2% 10.7% 88.1%* 8.7% 3.2%** 0.0% 100.0% never/rarely some of the time most/all of the time p ro po rti on o f p at ie nt s baseline 12 weeks epq8: how often do you feel picked on or judged because of your acne? 72.7% 13.0% 14.2% 86.6%* 8.3% 5.1%^^ 0.0% 100.0% p ro po rti on o f p at ie nt s baseline 12 weeks epq9: how concerned are you that your acne will affect your ability to reach your future goals (in school or work) and be the best you can be? 15.8% 25.7% 58.4% 16.8% 20.8% 62.4% 0.0% 100.0% not at all/a little somewhat quite a bit/very much p ro po rti on o f p at ie nt s baseline 12 weeks epq10: do you feel that your parents understand your acnerelated concerns? 72.3% 18.2% 9.5% 90.5%* 6.3% 3.2%# 0.0% 100.0% never/rarely some of the time most /all of the time p ro po rti on o f p at ie nt s baseline 12 weeks epq11: over the past 7 days, how often has worrying about or discomfort (itching/hurting) from acne affected your sleep? epq domain: emotional functioning influence of baseline demographics/disease characteristics on efficacy of an oral selective tyk2 inhibitor, bms-986165, in patients with moderate to severe plaque psoriasis: phase 2, randomized, placebo-controlled trial fall clinical dermatology conference • october 17–20, 2019 • las vegas, nv, usa k gordon,1 k papp,2 m gooderham,3 d thaçi,4 p foley,5 a morita,6 s kundu,7 r kisa,7 a napoli,7 s banerjee7 1medical college of wisconsin, milwaukee, wi, usa; 2k papp clinical research and probity medical research, waterloo, on, canada; 3skin centre for dermatology, queen’s university and probity medical research, peterborough, on, canada; 4university of lübeck, lübeck, germany; 5the university of melbourne, st vincent’s hospital melbourne & probity medical research, skin & cancer foundation inc, melbourne, victoria, australia; 6nagoya city university graduate school of medical sciences, nagoya, japan; 7bristol-myers squibb, princeton, nj, usa • psoriasis is a chronic, immune-mediated disorder characterized by symptoms that are associated with reduced health-related quality of life and decreased work productivity.1 • bms-986165 is an oral, selective inhibitor of tyrosine kinase 2 (tyk2),2,3 an enzyme that activates signal transducer and activator of transcription (stat)-dependent cytokine signaling pathways involved in psoriasis pathophysiology.4,5 • in a 12-week, phase 2 trial of bms-986165 in patients with moderate to severe plaque psoriasis6: ○ psoriasis area and severity index (pasi) 75 responses were highest at doses from 3 mg twice daily (bid) up to 12 mg once daily (qd; 67–75%) vs placebo at week 12 (7%; p0.001; primary endpoint) (table 1). ○ adverse events were generally mild to moderate and resulted in drug discontinuation in 4% of placebo patients and 2–7% of patients across the active doses. introduction • to report the influence of baseline demographics and disease characteristics on week 12 efficacy for the 3 most effective doses of bms-986165 (3 mg bid, 6 mg bid, and 12 mg qd). objective study design • adults with moderate to severe plaque psoriasis (body surface area [bsa] 10%, pasi score 12, static physician global assessment [spga] score 3) were randomized equally to bms-986165 (3 mg every other day, 3 mg qd, 3 mg bid, 6 mg bid, 12 mg qd) or placebo. • the treatment period was 12 weeks, with an additional 30-day off-treatment follow-up period for safety assessment, with efficacy measures collected post-treatment. subgroup analyses • subgroup analyses of efficacy endpoints were performed for the following baseline characteristics; randomization was not stratified by these characteristics. baseline demographics • weight (90 kg, 90 kg and 100 kg, 100 kg). • body mass index (bmi; 25 kg/m2 [underweight/normal], 25–30 kg/m2 [overweight], 30 kg/m2 [obese]). • age (18–45 years, 45 years). baseline disease • age of psoriasis onset (18 years, 18–45 years, 45 years, based on pediatric onset, and 2 peaks of psoriasis onset in adults). • dermatology life quality index (dlqi) score (10, 10–20, 20, corresponding approximately to the following categories of effect on the patient’s life: small to moderate, moderate to large, extremely large7). methods patients • in total, 267 patients were randomized and treated in the study. • patient demographics and disease characteristics were similar across treatment groups (table 2). subgroup analyses of efficacy endpoints • subgroup analyses are reported for patients treated with bms-986165 at doses shown to have the highest levels of efficacy (3 mg bid and above [n=134]). ○ there was a slight imbalance in the number of patients per treatment in each subgroup, as no stratification by subgroup was performed at randomization. baseline demographics • at week 12, the proportions of patients achieving pasi 75, pasi 90, or spga 0/1 were consistent across baseline demographic subgroups. ○ by weight (90 kg vs 90 kg; figure 1a): ∙ although pasi 90 response rates were generally lower in the 90 kg versus the 90 kg subgroup (22–38% vs 48–59%), the 95% cis overlapped between subgroups in each treatment group; differences among subgroups do not appear to be clinically meaningful. ∙ similar consistency in response rates was seen when a baseline weight cut-off of 100 kg was used (data not shown). ○ by bmi (25 kg/m2; 25–30 kg/m2; 30 kg/m2; table 3): ∙ although pasi 75 and pasi 90 response rates were numerically higher in the underweight/normal (25 kg/m2) bmi subgroup than in the overweight (25–30 kg/m2) or obese (30 kg/m2) subgroups, the 95% cis mostly overlapped across these subgroups; differences among the subgroups do not appear to be clinically meaningful. ∙ response rates for spga 0/1 were generally similar between bmi subgroups. ○ by age (18–45 years vs 45 years; figure 1b): ∙ although pasi 75, pasi 90, and spga 0/1 response rates were generally higher for the younger versus the older subgroup, the 95% cis all overlapped between the 2 subgroups; differences between the 2 subgroups do not appear to be clinically meaningful. results references 1. korman nj et al. dermatol online j. 2015;21:pii:13030/qt1x16v3dg. 2. tokarski js et al. j biol chem. 2015;290:11061-11074. 3. gillooly k et al. arthritis rheumatol. 2016;68(suppl 10):abstract 11l. 4. shaw mh et al. proc natl acad sci u s a. 2003;100:11594-11599. 5. harden jl et al. j autoimmun. 2015;64:66-73. 6. papp k et al. n engl j med. 2018;379:1313-1321. 7. hongbo y et al. j investig dermatol. 2005;125:659-664. 8. european medicines agency. guideline on clinical investigation of medicinal products indicated for the treatment of psoriasis. 2004. https://www.ema.europa.eu/documents/scientific-guideline/ guideline-clinical-investigation-medicinal-products-indicated-treatment-psoriasis_en.pdf. accessed december 17, 2018. acknowledgments the authors wish to acknowledge all investigators and patients involved in this study. this study was funded by bristol-myers squibb. professional medical writing and editorial assistance was provided by joanna wright, dphil, at caudex and was funded by bristol-myers squibb. disclosures kg: grant support and consulting fees: abbvie, boehringer ingelheim, bristol-myers squibb, celgene, eli lilly, janssen, novartis, and ucb; consulting fees: amgen, almirall, dermira, leo pharma, pfizer, and sun pharma. kp: grant support, consulting fees, advisory board, and speakers bureau: amgen, abbvie, boehringer ingelheim, eli lilly, janssen, kyowa hakko kirin, leo pharma, novartis, pfizer, ucb, and valeant; grant support, consulting fees, and scientific officer: akros; consulting fees: can-fite; grant support, consulting fees, advisory board, speakers bureau, and travel support: celgene; grant support, consulting fees, and advisory board: merck sharp & dohme, prcl, and takeda; grant support: anacor, glaxosmithkline, and meiji seika pharma; and grant support and consulting fees: coherus and dermira. mg: advisory board, principal investigator, and lecture fees: abbvie, galderma sa, leo pharma, pfizer, and regeneron pharmaceuticals; advisory board and lecture fees: actelion pharmaceuticals; principal investigator and consulting fees: akros pharma; advisory board, principal investigator, lecture fees, and consulting fees: amgen, boehringer ingelheim, celgene corporation, eli lilly, janssen, novartis pharmaceuticals, sanofi genzyme, and valeant pharmaceuticals; principal investigator: arcutis pharmaceuticals, bristol-myers squibb, dermira, glaxosmithkline, medimmune, merck and co., roche laboratories, and ucb; and principal investigator and lecture fees: glenmark. dt: grant support, lecture fees, consulting fees, and advisory board: abbvie; lecture fees, consulting fees, and advisory board: almirall, pfizer, regeneron, sandoz-hexal, sanofi, and ucb; consulting fees and advisory board: boehringer ingelheim; grant support, lecture fees, consulting fees, advisory board, and writing assistance: celgene and novartis; and lecture fees, consulting fees, advisory board, and writing assistance: eli lilly, leo pharma, and janssen-cilag. pf: grant support, advisory board, speakers bureau, and travel support: abbvie, celgene, csl limited, galderma, inova, janssen, leo pharma, eli lilly, novartis, pfizer, and sanofi; grant support and advisory board: amgen and sun pharma; grant support: boehringer ingelheim, celtaxsys, cutanea, dermira, genentech, and regeneron; grant support, advisory board, and speakers bureau: glaxosmithkline; grant support and consulting fees: bristol-myers squibb; grant support, speakers bureau, and travel support: roche. am: grant support and lecture fees: abbvie, eisai, kyowa hakko kirin, leo pharma, maruho, mitsubishi-tanabe pharm, novartis, and torii pharmaceutical; and lecture fees: celgene, eli lilly japan, and janssen pharmaceutical k.k. sk, rk, an, and sb: employees and shareholders: bristol-myers squibb. previously presented at the caribbean dermatology symposium, held january 15–19, 2019. table 1: efficacy of bms-986165 at week 12 (nri). placebo (n=45) bms-986165 3 mg qod (n=44) 3 mg qd (n=44) 3 mg bid (n=45) 6 mg bid (n=45) 12 mg qd (n=44) primary endpoint: pasi 75 patients, n (%) 3 (7) 4 (9) 17 (39) 31 (69) 30 (67) 33 (75) p value vs placebo 0.49 0.001 0.001 0.001 0.001 secondary endpoints pasi 90 patients, n (%) 1 (2) 3 (7) 7 (16) 20 (44) 20 (44) 19 (43) difference vs placebo, % (95% ci) 5 (–16 to 25) 14 (–7 to 33) 42 (21–60) 42 (21–60) 41 (20–58) pasi 100 patients, n (%) 0 (0) 1 (2) 0 (0) 4 (9) 8 (18) 11 (25) difference vs placebo, % (95% ci) 2 (–18 to 23) 9 (–13 to 30) 18 (–4 to 38) 25 (4–44) spga 0/1 patients, n (%) 3 (7) 9 (20) 17 (39) 34 (76) 29 (64) 33 (75) difference vs placebo, % (95% ci) 14 (–7 to 33) 32 (11–50) 69 (51–83) 58 (38–74) 68 (50–82) dlqi 0/1 patients, n (%) 2 (4) 7 (16) 7 (16) 19 (42) 27 (60) 28 (64) difference vs placebo, % (95% ci) 12 (–2 to 26) 12 (–2 to 26) 38 (20–54) 56 (38–71) 59 (41–74) data have been rounded to the nearest integer. for patients who discontinued early or who had a missing value at any time point, data were imputed as a non-response at that time point, regardless of the status of response at the time of discontinuation. the numbers of patients with nri in each group were as follows: for pasi endpoints: placebo n=11, 3 mg qod n=6, 3 mg qd n=3, 3 mg bid n=1, 6 mg bid n=5, and 12 mg qd n=1; for spga 0/1: placebo n=11, 3 mg qod n=6, 3 mg qd n=6, 3 mg bid n=1, 6 mg bid n=6, and 12 mg qd n=1; for dlqi 0/1: placebo n=11, 3 mg qod n=6, 3 mg qd n=3, 3 mg bid n=2, 6 mg bid n=5, and 12 mg qd n=1. p values for endpoints other than the primary endpoint are not reported because these values have not been adjusted for multiple comparisons; 95% cis are unadjusted. from n engl j med, papp ka et al, phase 2 trial of selective tyrosine kinase 2 inhibition in psoriasis, vol 379, pages 1313–1321. copyright © 2018 massachusetts medical society. reprinted with permission from massachusetts medical society. bid=twice daily; ci=confidence interval; dlqi 0/1=dermatology life quality index score of 0 or 1 (scores on the dlqi range from 0 to 30, with higher scores indicating worse quality of life); nri=non-responder imputation; pasi 75=75% improvement in psoriasis area and severity index score; pasi 90=90% improvement in psoriasis area and severity index score; pasi 100=100% improvement in psoriasis area and severity index score; qd=once daily; qod=every other day; spga 0/1=static physician global assessment score of 0 or 1 (scores on the spga range from 0 to 5, with higher scores indicating greater disease severity). table 2: demographic and clinical characteristics of patients at baseline. characteristic total (n=267) placebo (n=45) bms-986165 3 mg qod (n=44) 3 mg qd (n=44) 3 mg bid (n=45) 6 mg bid (n=45) 12 mg qd (n=44) demographic characteristics age, years 45±13 46±12 41±12 45±14 46±15 43±13 47±12 sex, male, n (%) 194 (73) 37 (82) 36 (82) 30 (68) 26 (58) 35 (78) 30 (68) race, n (%)* white 225 (84) 40 (89) 35 (80) 39 (89) 39 (87) 35 (78) 37 (84) asian 36 (13) 5 (11) 6 (14) 5 (11) 5 (11) 9 (20) 6 (14) other 6 (2) 0 (0) 3 (7) 0 (0) 1 (2) 1 (2) 1 (2) body weight, kg 88±20 96±21 90±18 87±22 84±18 84±19 88±24 bmi, kg/m2 29±5 30±6 29±6 29±5 28±5 27±5 29±5 clinical characteristics median (range) duration of disease, years 15 (1–61) 18 (2–48) 18 (1–52) 13 (2–60) 13 (1–61) 15 (1–55) 20 (1–47) previous use of biologic agent, n (%) 115 (43) 20 (44) 19 (43) 19 (43) 19 (42) 20 (44) 18 (41) pasi score† 18±6 19±6 17±4 18±6 19±8 18±6 18±5 dlqi score‡ 12±7 13±7 12±8 12±7 13±5 11±6 13±7 bsa, %§ 23±13 24±13 20±8 23±17 24±15 25±13 21±12 plus-minus values are mean ± sd. formal statistical analysis was not performed to evaluate between-group differences. data have been rounded to the nearest integer. percentages may not total 100 because of rounding. *race was reported by the patients on a questionnaire at screening or baseline. †pasi scores range from 0 to 72, with higher scores indicating greater severity of psoriasis. ‡dlqi scores range from 0 to 30, with higher scores indicating worse quality of life. §percentage of bsa affected by psoriasis. adapted from n engl j med, papp ka et al, phase 2 trial of selective tyrosine kinase 2 inhibition in psoriasis, vol 379, pages 1313–1321. copyright © 2018 massachusetts medical society. reprinted with permission from massachusetts medical society. bid=twice daily; bmi=body mass index; bsa=body surface area; dlqi=dermatology life quality index; pasi=psoriasis area and severity index; qd=once daily; qod=every other day; sd=standard deviation. baseline disease • at week 12, the proportions of patients achieving pasi 75, pasi 90, or spga 0/1 were generally consistent across baseline disease subgroups. ○ by age of onset (18 years, 18–45 years, 45 years; figure 2a): ∙ although some variability in pasi 75 and pasi 90 response rates between subgroups was seen, the 95% cis all overlapped between subgroups within each treatment group; differences among subgroups within each treatment arm do not appear to be clinically meaningful. ∙ response rates for spga 0/1 were generally similar across age of onset subgroups. ○ by pasi score (20, 20; figure 2b): ∙ response rates for the subgroup of patients with pasi scores 20 were similar to those for patients with pasi scores 20. ○ a general consistency in responses was seen regardless of bmi, disease duration, or previous biologic use (table 3), or musculoskeletal symptoms, spga score, dlqi, or bsa (table 4). • bsa (20%, 20%, to indicate less/more severe disease8). • pasi score (20, 20, to indicate less/more severe disease8). • disease duration (15 years, 15 years, based on median duration of disease in the overall trial population6). • musculoskeletal symptoms (no, yes) such as joint pain, heel pain, or back pain. • spga score (3 [moderate], 4–5 [severe]). • previous biologic use (no, yes). statistical analysis • response rates and 95% confidence intervals (cis) are presented in the bar charts. • missing data were imputed using non-responder imputation; patients who discontinued early or who had a missing value at any time point had data imputed as a non-response at that time point, regardless of the status of response at the time of discontinuation. 90 kg 45 years18–45 years 90 kg a b pasi 75 placebo weight 90 kg (n=16): 18.8% (95% ci: 4.0–45.6) weight 90 kg (n=29): 0% (95% ci: 0.0–11.9) 29n = 16 3 mg bid 27 18 25 19 81 53 72.4 62.5 74.1 55.6 76.0 73.7 74.1 64.2 90 100 80 70 60 50 40 30 20 10 0 6 mg bid 12 mg qd combined* r es po nd er s at w ee k 12 (% ) 48.3 37.5 59.3 22.2 48.0 36.8 51.9 32.1 pasi 90 90 100 80 70 60 50 40 30 20 10 0 placebo weight 90 kg (n=16): 6.3% (95% ci: 0.2–30.2) weight 90 kg (n=29): 0% (95% ci: 0.0–11.9) 29n = 16 27 18 25 19 81 53 3 mg bid 6 mg bid 12 mg qd combined* r es po nd er s at w ee k 12 (% ) 72.4 81.3 63.0 66.7 80.0 68.4 71.6 71.7 spga 0/1 90 100 80 70 60 50 40 30 20 10 0 placebo weight 90 kg (n=16): 12.5% (95% ci: 1.6–38.3) weight 90 kg (n=29): 3.4% (95% ci: 0.1–17.8) 29n = 16 27 18 25 19 81 53 3 mg bid 6 mg bid 12 mg qd combined* 22n = 23 3 mg bid 24 21 20 24 66 68 6 mg bid 12 mg qd combined* 22n = 23 24 21 20 24 66 68 3 mg bid 6 mg bid 12 mg qd combined* 22n = 23 24 21 20 24 66 68 3 mg bid 6 mg bid 12 mg qd combined* r es po nd er s at w ee k 12 (% ) pasi 75 placebo 18–45 years (n=20): 5.0% (95% ci: 0.1–24.9) 45 years (n=25): 8.0% (95% ci: 1.0–26.0) 77.3 60.9 66.7 66.7 80.0 70.8 74.2 66.2 90 100 80 70 60 50 40 30 20 10 0 r es po nd er s at w ee k 12 (% ) pasi 90 90 100 80 70 60 50 40 30 20 10 0 placebo 18–45 years (n=20): 0% (95% ci: 0.0–16.8) 45 years (n=25): 4.0% (95% ci: 0.1–20.4) 54.5 34.8 58.3 28.6 45.0 41.7 53.0 35.3 r es po nd er s at w ee k 12 (% ) spga 0/1 90 100 80 70 60 50 40 30 20 10 0 placebo 18–45 years (n=20): 5.0% (95% ci: 0.1–24.9) 45 years (n=25): 8.0% (95% ci: 1.0–26.0) 77.3 73.9 70.8 57.1 85.0 66.7 77.3 66.2 r es po nd er s at w ee k 12 (% ) figure 1: efficacy of bms-986165: endpoints at week 12 by baseline demographic characteristics: a) weight and b) age. error bars are 95% exact cis; data labels above each bar are the response rates. *bms-986165 3 mg bid, 6 mg bid, and 12 mg qd combined. bid=twice daily; ci=confidence interval; pasi 75=75% improvement in psoriasis area and severity index score; pasi 90=90% improvement in psoriasis area and severity index score; qd=once daily; spga 0/1=static physician global assessment score of 0 or 1. a 18 years 18–45 years 45 years pasi 20 pasi 20 50.0 45.8 39.5 33.348.537.548.3 41.2 69.0 68.8 72.7 50.0 80.0 71.9 65.8 73.5 pasi 75b placebo 20 (n=31): 0% (95% ci: 0.0–11.2) 20 (n=14): 21.4% (95% ci: 4.7–50.8) r es po nd er s at w ee k 12 (% ) 29n = 16 33 12 34 10 96 38 90 100 80 70 60 50 40 30 20 10 0 90 100 80 70 60 50 40 30 20 10 0 90 100 80 70 60 50 40 30 20 10 0 pasi 90 placebo 20 (n=31): 0% (95% ci: 0.0–11.2) 20 (n=14): 7.1% (95% ci: 0.2–33.9) r es po nd er s at w ee k 12 (% ) 29n = 16 33 12 34 10 96 38 80.0 75.0 63.2 41.7 72.768.8 79.3 73.5 spga 0/1 placebo 20 (n=31): 3.2% (95% ci: 0.1–16.7) 20 (n=14): 14.3% (95% ci: 1.8–42.8) r es po nd er s at w ee k 12 (% ) 29n = 16 33 12 34 10 96 38 r es po nd er s at w ee k 12 (% ) pasi 75 13 21 3 mg bid 6 mg bid 12 mg qd combined* 11 16 26 3 9 29 6 38 76 20n = 76.9 71.4 54.5 50.0 76.9 66.7 77.8 75.9 66.7 65.8 75.0 60.0 90 100 80 70 60 50 40 30 20 10 0 placebo 18 years (n=14): 0% (95% ci: 0.0–23.2) 18–45 years (n=27): 11.1% (95% ci: 2.4–29.2) 45 years (n=4): 0% (95% ci: 0.0–60.2) pasi 90 3 mg bid 6 mg bid 12 mg qd combined* 13 21 11 16 26 3 9 29 6 38 76 20n = 53.8 42.9 36.4 18.8 61.5 33.3 44.4 48.3 16.7 36.8 51.3 30.0 90 100 80 70 60 50 40 30 20 10 0r es po nd er s at w ee k 12 (% ) placebo 18 years (n=14): 0% (95% ci: 0.0–23.2) 18–45 years (n=27): 3.7% (95% ci: 0.1–19.0) 45 years (n=4): 0% (95% ci: 0.0–60.2) spga 0/1 3 mg bid 6 mg bid 12 mg qd combined* 13n = 21 11 16 26 3 9 29 6 38 76 20 84.6 71.4 72.7 56.3 69.2 66.7 77.8 75.9 66.7 71.1 72.4 70.090 100 80 70 60 50 40 30 20 10 0r es po nd er s at w ee k 12 (% ) placebo 18 years (n=14): 0% (95% ci: 0.0–23.2) 18–45 years (n=27): 11.1% (95% ci: 2.4–29.2) 45 years (n=4): 0% (95% ci: 0.0–60.2) 3 mg bid 6 mg bid 12 mg qd combined* 3 mg bid 6 mg bid 12 mg qd combined* 3 mg bid 6 mg bid 12 mg qd combined* figure 2: efficacy of bms-986165: endpoints at week 12 by baseline disease characteristics: a) age at onset of psoriasis and b) pasi score. error bars are 95% exact cis; data labels above each bar are the response rates. *bms-986165 3 mg bid, 6 mg bid, and 12 mg qd combined. bid=twice daily; ci=confidence interval; pasi=psoriasis area and severity index; pasi 75=75% improvement in psoriasis area and severity index score; pasi 90=90% improvement in psoriasis area and severity index score; qd=once daily; spga 0/1=static physician global assessment score of 0 or 1. • in patients with moderate to severe plaque psoriasis, bms-986165 demonstrated consistent efficacy at oral doses 3 mg bid regardless of baseline weight, bmi, or age; age at onset; baseline disease severity (pasi, musculoskeletal symptoms, spga, dlqi, bsa) or duration; or previous biologic use. ○ although variation in response was seen among some subgroups, the 95% cis mostly overlapped between complementary subgroups within treatment groups and the differences did not appear to be clinically meaningful. ○ small patient numbers may underlie the fluctuations observed. • two global, randomized, placebo-controlled and active-comparator phase 3 trials in psoriasis are underway to confirm these findings (poetyk pso program; clinicaltrials.gov identifiers: nct03624127 and nct03611751). conclusions table 4: efficacy of bms-986165: endpoints at week 12 by disease characteristics at baseline. endpoint dose musculoskeletal symptoms spga score dlqi bsa no yes 3 (moderate) 4–5 (severe) <10 10–<20 20 20% 20% pasi 75 3 mg bid n=3464.7 (46.5–80.3) n=11 81.8 (48.2–97.7) n=29 65.5 (45.7–82.1) n=16 75.0 (47.6–92.7) n=14 57.1 (28.9–82.3) n=26 73.1 (52.2–88.4) n=5 80.0 (28.4–99.5) n=26 69.2 (48.2–85.7) n=19 68.4 (43.4–87.4) 6 mg bid n=3467.6 (49.5–82.6) n=11 63.6 (30.8–89.1) n=32 65.6 (46.8–81.4) n=12 75.0 (42.8–94.5) n=19 84.2 (60.4–96.6) n=22 50.0 (28.2–71.8) n=4 75.0 (19.4–99.4) n=19 84.2 (60.4–96.6) n=26 53.8 (33.4–73.4) 12 mg qd n=2975.9 (56.5–89.7) n=15 73.3 (44.9–92.2) n=28 71.4 (51.3–86.8) n=16 81.3 (54.4–96.0) n=19 78.9 (54.4–93.9) n=14 78.6 (49.2–95.3) n=11 63.6 (30.8–89.1) n=28 75.0 (55.1–89.3) n=16 75.0 (47.6–92.7) combined* n=9769.1 (58.9–78.1) n=37 73.0 (55.9–86.2) n=89 67.4 (56.7–77.0) n=44 77.3 (62.2–88.5) n=52 75.0 (61.1–86.0) n=62 66.1 (53.0–77.7) n=20 70.0 (45.7–88.1) n=73 75.3 (63.9–84.7) n=61 63.9 (50.6–75.8) pasi 90 3 mg bid n=3447.1 (29.8–64.9) n=11 36.4 (10.9–69.2) n=29 37.9 (20.7–57.7) n=16 56.3 (29.9–80.2) n=14 35.7 (12.8–64.9) n=26 50.0 (29.9–70.1) n=5 40.0 (5.3–85.3) n=26 50.0 (29.9–70.1) n=19 36.8 (16.3–61.6) 6 mg bid n=3444.1 (27.2–62.1) n=11 45.5 (16.7–76.6) n=32 43.8 (26.4–62.3) n=12 50.0 (21.1–78.9) n=19 68.4 (43.4–87.4) n=22 22.7 (7.8–45.4) n=4 50.0 (6.8–93.2) n=19 57.9 (33.5–79.7) n=26 34.6 (17.2–55.7) 12 mg qd n=2944.8 (26.4–64.3) n=15 40.0 (16.3–67.7) n=28 42.9 (24.5–62.8) n=16 43.8 (19.8–70.1) n=19 42.1 (20.3–66.5) n=14 42.9 (17.7–71.1) n=11 45.5 (16.7–76.6) n=28 35.7 (18.6–55.9) n=16 56.3 (29.9–80.2) combined* n=9745.4 (35.2–55.8) n=37 40.5 (24.8–57.9) n=89 41.6 (31.2–52.5) n=44 50.0 (34.6–65.4) n=52 50.0 (35.8–64.2) n=62 38.7 (26.6–51.9) n=20 45.0 (23.1–68.5) n=73 46.6 (34.8–58.6) n=61 41.0 (28.6–54.3) spga 0/1 3 mg bid n=3470.6 (52.5–84.9) n=11 90.9 (58.7–99.8) n=29 75.9 (56.5–89.7) n=16 75.0 (47.6–92.7) n=14 64.3 (35.1–87.2) n=26 80.8 (60.6–93.4) n=5 80.0 (28.4–99.5) n=26 80.8 (60.6–93.4) n=19 68.4 (43.4–87.4) 6 mg bid n=3467.6 (49.5–82.6) n=11 54.5 (23.4–83.3) n=32 62.5 (43.7–78.9) n=12 75.0 (42.8–94.5) n=19 78.9 (54.4–93.9) n=22 50.0 (28.2–71.8) n=4 75.0 (19.4–99.4) n=19 78.9 (54.4–93.9) n=26 53.8 (33.4–73.4) 12 mg qd n=2975.9 (56.5–89.7) n=15 73.3 (44.9–92.2) n=28 75.0 (55.1–89.3) n=16 75.0 (47.6–92.7) n=19 73.7 (48.8–90.9) n=14 85.7 (57.2–98.2) n=11 63.6 (30.8–89.1) n=28 75.0 (55.1–89.3) n=16 75.0 (47.6–92.7) combined* n=9771.1 (61.0–79.9) n=37 73.0 (55.9–86.2) n=89 70.8 (60.2–79.9) n=44 75.0 (59.7–86.8) n=52 73.1 (59.0–84.4) n=62 71.0 (58.1–81.8) n=20 70.0 (45.7–88.1) n=73 78.1 (66.9–86.9) n=61 63.9 (50.6–75.8) data are shown as response rate, % (95% exact ci). data for the placebo arm are as follows: musculoskeletal symptoms: no (n=24): pasi 75, 12.5 (2.7–32.4); pasi 90, 4.2 (0.1–21.1); spga 0/1, 12.5 (2.7–32.4); yes (n=21): pasi 75, 0.0 (0.0–16.1); pasi 90, 0.0 (0.0–16.1); spga 0/1, 0.0 (0.0–16.1). spga score: 3 (n=29): pasi 75, 3.4 (0.1–17.8); pasi 90, 0.0 (0.0–11.9); spga 0/1, 6.9 (0.8–22.8); 4–5 (n=16): pasi 75, 12.5 (1.6–38.3); pasi 90, 6.3 (0.2–30.2); spga 0/1, 6.3 (0.2–30.2). dlqi: <10 (n=14): pasi 75, 0.0 (0.0–23.2); pasi 90, 0.0 (0.0–23.2); spga 0/1, 7.1 (0.2–33.9); 10–<20 (n=23): pasi 75, 8.7 (1.1–28.0); pasi 90, 0.0 (0.0–14.8); spga 0/1, 8.7 (1.1–28.0); 20 (n=8): pasi 75, 12.5 (0.3–52.7); pasi 90, 12.5 (0.3–52.7); spga 0/1, 0.0 (0.0–36.9). bsa: 20% (n=19): pasi 75, 0.0 (0.0–17.6); pasi 90, 0.0 (0.0–17.6); spga 0/1, 5.3 (0.1–26.0); 20% (n=26): pasi 75, 11.5 (2.4–30.2); pasi 90, 3.8 (0.1–19.6); spga 0/1, 7.7 (0.9–25.1). *bms-986165 3 mg bid, 6 mg bid, and 12 mg qd combined. bid=twice daily; bsa=body surface area; ci=confidence interval; dlqi=dermatology life quality index; pasi 75=75% improvement in psoriasis area and severity index score; pasi 90=90% improvement in psoriasis area and severity index score; qd=once daily; spga 0/1=static physician global assessment score of 0 or 1. table 3: efficacy of bms-986165: endpoints at week 12 by baseline bmi and disease duration, and previous biologic use. endpoint dose bmi disease duration, years previous biologic use per iwrs 25 kg/m2 25–30 kg/m2 30 kg/m2 15 15 no yes pasi 75 3 mg bid n=1384.6 (54.6–98.1) n=16 56.3 (29.9–80.2) n=16 68.8 (41.3–89.0) n=25 72.0 (50.6–87.9) n=20 65.0 (40.8–84.6) n=26 65.4 (44.3–82.8) n=19 73.7 (48.8–90.9) 6 mg bid n=1973.7 (48.8–90.9) n=11 63.6 (30.8–89.1) n=15 60.0 (32.3–83.7) n=22 68.2 (45.1–86.1) n=23 65.2 (42.7–83.6) n=25 80.0 (59.3–93.2) n=20 50.0 (27.2–72.8) 12 mg qd n=988.9 (51.8–99.7) n=19 73.7 (48.8–90.9) n=16 68.8 (41.3–89.0) n=13 61.5 (31.6–86.1) n=31 80.6 (62.5–92.5) n=26 80.8 (60.6–93.4) n=18 66.7 (41.0–86.7) combined* n=4180.5 (65.1–91.2) n=46 65.2 (49.8–78.6) n=47 66.0 (50.7–79.1) n=60 68.3 (55.0–79.7) n=74 71.6 (59.9–81.5) n=77 75.3 (64.2–84.4) n=57 63.2 (49.3–75.6) pasi 90 3 mg bid n=1376.9 (46.2–95.0) n=16 18.8 (4.0–45.6) n=16 43.8 (19.8–70.1) n=25 48.0 (27.8–68.7) n=20 40.0 (19.1–63.9) n=26 50.0 (29.9–70.1) n=19 36.8 (16.3–61.6) 6 mg bid n=19 57.9 (33.5–79.7) n=11 54.5 (23.4–83.3) n=15 20.0 (4.3–48.1) n=22 54.5 (32.2–75.6) n=23 34.8 (16.4–57.3) n=25 60.0 (38.7–78.9) n=20 25.0 (8.7–49.1) 12 mg qd n=9 66.7 (29.9–92.5) n=19 36.8 (16.3–61.6) n=16 37.5 (15.2–64.6) n=13 23.1 (5.0–53.8) n=31 51.6 (33.1–69.8) n=26 42.3 (23.4–63.1) n=18 44.4 (21.5–69.2) combined* n=41 65.9 (49.4–79.9) n=46 34.8 (21.4–50.2) n=47 34.0 (20.9–49.3) n=60 45.0 (32.1–58.4) n=74 43.2 (31.8–55.3) n=77 50.6 (39.0–62.2) n=57 35.1 (22.9–48.9) spga 0/1 3 mg bid n=1376.9 (46.2–95.0) n=16 68.8 (41.3–89.0) n=16 81.3 (54.4–96.0) n=25 68.0 (46.5–85.1) n=20 85.0 (62.1–96.8) n=26 61.5 (40.6–79.8) n=19 94.7 (74.0–99.9) 6 mg bid n=1963.2 (38.4–83.7) n=11 63.6 (30.8–89.1) n=15 66.7 (38.4–88.2) n=22 63.6 (40.7–82.8) n=23 65.2 (42.7–83.6) n=25 72.0 (50.6–87.9) n=20 55.0 (31.5–76.9) 12 mg qd n=988.9 (51.8–99.7) n=19 78.9 (54.4–93.9) n=16 62.5 (35.4–84.8) n=13 53.8 (25.1–80.8) n=31 83.9 (66.3–94.5) n=26 80.8 (60.6–93.4) n=18 66.7 (41.0–86.7) combined* n=4173.2 (57.1–85.8) n=46 71.7 (56.5–84.0) n=47 70.2 (55.1–82.7) n=60 63.3 (49.9–75.4) n=74 78.4 (67.3–87.1) n=77 71.4 (60.0–81.2) n=57 71.9 (58.5–83.0) data are shown as response rate, % (95% exact ci). data for the placebo arm are as follows: bmi: 25 kg/m2 (n=6): pasi 75, 0.0 (0.0–45.9); pasi 90, 0.0 (0.0–45.9); spga 0/1, 0.0 (0.0–45.9); 25–30 kg/m2 (n=14): pasi 75, 7.1 (0.2–33.9); pasi 90, 0.0 (0.0–23.2); spga 0/1, 7.1 (0.2–33.9); 30 kg/m2 (n=25): pasi 75, 8.0 (1.0–26.0); pasi 90, 4.0 (0.1–20.4); spga 0/1, 8.0 (1.0–26.0). disease duration: 15 years (n=16): pasi 75, 6.3 (0.2–30.2); pasi 90, 0.0 (0.0–20.6); spga 0/1, 12.5 (1.6–38.3); 15 years (n=29): pasi 75, 6.9 (0.8–22.8); pasi 90, 3.4 (0.1–17.8); spga 0/1, 3.4 (0.1–17.8). previous biologic use per iwrs: no (n=25): pasi 75, 4.0 (0.1–20.4); pasi 90, 0.0 (0.0–13.7); spga 0/1, 8.0 (1.0–26.0); yes (n=20): pasi 75, 10.0 (1.2–31.7); pasi 90, 5.0 (0.1–24.9); spga 0/1, 5.0 (0.1–24.9). *bms-986165 3 mg bid, 6 mg bid, and 12 mg qd combined. bid=twice daily; bmi=body mass index; ci=confidence interval; iwrs=interactive web response system; pasi 75=75% improvement in psoriasis area and severity index score; pasi 90=90% improvement in psoriasis area and severity index score; qd=once daily; spga 0/1=static physician global assessment score of 0 or 1. scientific content on-demand copies of this poster obtained through quick response (qr) code are for personal use only and may not be reproduced without permission from fall clinical dermatology conference and the authors of this poster. links are valid for 30 days after the congress presentation date. to receive a copy of this poster scan qr code via a barcode reader application fc 2019 util poster -09272019 findings from a large us registry study to assess the real-world utility of a non-invasive gene expression test designed to rule out primary cutaneous melanoma brook brouha, md, phd1, laura k. ferris, md, phd2, maral k. skelsey, md3, gary peck, md4, zuxu yao, phd5 and burkhard jansen, md5 1west dermatology, la jolla, ca, usa; 2department of dermatology, university of pittsburgh, pittsburgh, pa, usa; 3department of dermatology, georgetown university school of medicine, washington, dc, usa; 4dermatologic surgery center of washington, chevy chase, md, usa; 5dermtech, inc, la jolla, ca, usa methods synopsis 1. gerami p et al. development and validation of a non-invasive 2-gene molecular assay for cutaneous melanoma. j am acad dermatol, 2017;76(1)114-120.e2 2. ferris l et al. real-world performance and utility of a non-invasive gene expression assay to evaluate melanoma risk in pigmented lesions. mel res, 2018; 28(5):478-482. 3. hornberger j and siegel d. economic analysis of a non-invasive molecular pathologic assay for pigmented skin lesions. jama dermatol, 2018; 154(9)1-8. 4. ferris l et al. impact on clinical practice of a non-invasive gene expression melanoma rule-out test: 12 month follow-up of negative test results and utility data from a large us registry study. dermatol online j, 2019; 25(5):1-8. • to assess the real-world use and utility of the pla [1-4] and determine, if clinicians follow the guidance of the test the pigmented lesion assay (pla) analyzes gene expression to objectively rule out melanoma. the test uses a non-invasive adhesive patch–based sample collection platform that enables guidance on biopsy decisions and elevates pigmented lesion management beyond what can be visually ascertained. the test’s negative predictive value of >99%, and rapid, painless application make it an attractive pre-biopsy solution. it reduces biopsies by 90% while improving care and reducing cost. this registry study (53 us dermatology offices, 90 providers, median patient age 48 years, 60.80% female patients) assesses real-world utility to determine if the pla changes clinical practice. the pla assessed 3,418 concerning pigmented skin lesions. three hundred and twenty-four lesions (9.48%) were pla(+) and 3,094 (90.52%) were negative. a pla test result is positive if linc, prame, or both target genes are detected. these molecular pathology findings are known to correspond with histopathology findings of in situ or invasive primary melanoma in 7%, 50%, and 93%, respectively. the 9.48% pla(+) cases consisted of 5.15% linc-only, 1.93% prame-only, and 2.40% linc and prame double positive cases. notably, pla(+) lesions were almost universally surgically biopsied (97.53%), while pla(-) cases were nearly always monitored and not biopsied (99.94%). these studies demonstrate that the pla has true clinical value in community-based practices where providers make important decisions based on the test’s results. pigmented lesions with pla(+) test results are subjected to surgical biopsies, whereas pla(-) lesions are followed clinically and not biopsied. we here expand on pla follow-up and utility findings previously reported that also included long-term follow-up and us registry data; approval was obtained from the western-copernicus group’s independent review board [2, 4]. we report on a one-year pla registry study initiated in june of 2018 with data acquisition between july of 2018 and june of 2019. fifty-three us dermatology practices (and 90 providers within these practices including board certified dermatologists, primary care physicians, physician assistants, and nurse practitioners) participated in the registry and reported on 3,418 pigmented lesions clinically suspicious for melanoma that were evaluated by pla. the pla results and management decisions (clinical monitoring of a given lesion or biopsy) were correlated. all lesion samples were obtained using a non-invasive adhesive skin collection kit (dermtech, la jolla, ca) according to package insert instructions. in brief, a selected pigmented lesion suspicious for melanoma is cleansed with an ethanol swab and dried, and four adhesive patches from the sample collection kit are applied sequentially to collect one sample. gentle pressure from about 5 circular thumb motions ensures contact between the adhesive and skin; no wait time is required. to enable separation of lesional from non-lesional surrounding skin tissue, the lesion is demarcated with a marker pen on each one of the applied adhesive patches. patches are placed in a pre-addressed courier envelope and shipped to a central processing laboratory without need for refrigeration or special handling. the sample collection process takes about 1-2 minutes. a molecular pathology report is generally available within 48-72 hours. objectives conclusions references conflict of interest disclosures: bb, lf, ms and gp are advisors and/or investigators, bj and zy are employees of dermtech • findings from this large us pigmented lesion assay (pla) registry study of 3,418 cases of pigmented skin lesions clinically suspicious of melanoma and assessed by pla confirm the test’s high clinical utility and high negative predictive value. • clinicians follow the guidance of the test and rely on its performance. • pla negative lesions are monitored clinically and not biopsied in 99.94% of cases. • pla positive lesions are biopsied as intended in 97.53% of cases. • the pla helps clinicians avoid over 90% of unnecessary surgical procedures while missing fewer melanomas. results findings from a large us pigmented lesion assay registry study (53 us dermatology offices, 90 providers) of 3,418 patients and their pigmented skin lesions clinically suspicious for melanoma and evaluated by pla are presented. the median patient age was 48 years; 60.80% of patients were female and 39.20% were male. overall, most lesions (55.18%) evaluated by pla were located on the trunk, followed by locations on extremities (27.27%) and locations in face / head / neck areas (17.55%). figure 1 provides details on lesion locations in male and female patients demonstrating similar lesion locations in face / head / neck areas (19.00% and 17.35%, respectively) while female patients’ pigmented lesions evaluated by pla were more often located on extremities (32.44% versus 18.70% in male patients). figure 1. anatomical locations of pigmented lesions evaluated by pla in male and female patients. of 3,418 pigmented skin lesions clinically suspicious for melanoma and assessed by pla, 324 lesions (9.48%) were pla(+) and 3,094 (90.52%) were negative (figure 2). pla test results are positive if linc, prame, or both target genes are detected; these molecular pathology findings are known to correspond with histopathology findings of in situ or invasive primary melanoma in 7%, 50%, and 93%, respectively [14]. the 9.48% pla(+) cases consisted of 5.15% linc only, 1.93% prame only, and 2.40% linc and prame double positive cases (figure 2). notably, pla(+) lesions were surgically biopsied in 97.53% while pla(-) cases were clinically monitored and not biopsied in 99.94% of the cases. pla(+) cases with detectable levels of both target genes or detectable levels of prame were surgically biopsied in all cases, while 95.45% of linc-only cases were biopsied (figure 2). figure 2. pla registry study outline and a summary on how pla test results guide biopsy decisions. of a total of 3,094 pla(-) lesions, only two (0.06%) were subjected to surgical procedures. one was a melanocytic nevus subjected to a shave/scoop biopsy and the second was a squamous cell carcinoma in situ removed by mohs surgery. the remaining 3,092 pla(-) cases were monitored clinically and not biopsied or excised. of these, 179 (5.79%) were scheduled for follow-up in three months, whereas 1,198 (38.75%) and 1,504 (48.64%) were scheduled for follow-up in 6 and 12 months, respectively. in addition, 211 patients (6.82%) were scheduled for followup at other time frames. the vast majority (316 of 324 or 97.53%) of pla(+) cases (9.48% of all pigmented lesions assessed by pla in this study), were surgically biopsied as described. of these biopsies, 51.58% were shave/scoop, 10.13% were punch, and 38.29% were excisional procedures. table 1 summarizes the types of biopsy procedures employed and provides further details on how not only pla results, but the detection of either one or both of the target genes affects the type of biopsy procedure selected. all 8 pla positive cases not subjected to biopsies were linc-only cases, which have a lower probability of being melanomas histopathologically [2]. table 1. biopsy type after pla. gene expression test characteristics and selected biopsy types after pla(-) and pla(+) test results (n=3,418). the pla is positive if either linc or prame or both linc and prame are detected. linc positive, prame positive and linc and prame double positive cases correlate with a histopathologic diagnosis of melanoma in 7%, 50%, and 93%, respectively [2]. introduction ■ tapinarof (vtama®; dermavant sciences, inc., usa) is a first-in-class, nonsteroidal, topical, aryl hydrocarbon receptor agonist approved by the food and drug administration for the treatment of plaque psoriasis in adults, and under investigation for the treatment of plaque psoriasis in children down to 2 years of age and for atopic dermatitis (ad) in adults and children down to 2 years of age1 ■ tapinarof cream 1% once daily (qd) demonstrated significant efficacy versus vehicle and was well tolerated in adults with mild to severe plaque psoriasis in two identical, 12-week, pivotal phase 3 trials, psoaring 1 (nct03956355) and psoaring 2 (nct03983980)2 ■ in the long-term extension trial, psoaring 3 (nct04053387), tapinarof was well tolerated and demonstrated a high rate of complete disease clearance, ~4-month remittive effect off therapy, and durability on therapy for up to 52 weeks3 ■ topical agents that are locally effective with minimal systemic exposure are desirable for dermatologic conditions ■ there is a need for efficacious, non-steroidal topical therapies for patients with psoriasis, without restrictions relating to duration, extent of use, and application sites ■ in a phase 2a trial, topical application of tapinarof cream 1% qd under maximal use conditions in patients with extensive psoriasis (up to 46% body surface area [bsa] involvement) resulted in minimal systemic exposure4 objective ■ to evaluate the hypothesis that there is no relationship between tapinarof plasma exposure and either safety or efficacy methods trial design ■ analyses included data from 4 clinical trials of tapinarof in patients with ad or plaque psoriasis across a range of doses, patient populations, and bsa involvement (table 1) table 1. clinical trials included in tapinarof exposure–response analyses patients with ad patients with plaque psoriasis phase 2b dose-finding trial (n=247)5 phase 2a maximal-use trial (n=21)4 pivotal phase 3 trials2 psoaring 1 (n=510) psoaring 2 (n=515) trial design randomized, double-blind, vehicle-controlled open-label randomized, double-blind, vehicle-controlled eligibility criteria patient population ad with iga score ≥3 plaque psoriasis with pga score ≥3 plaque psoriasis with pga score ≥2 age 12–65 years 18–75 years 18–75 years bsa involvement 5%–35% ≥20% 3%–20% trial drug tapinarof cream: 0.5% qd, 0.5% bid, 1% qd, 1% bid vehicle cream: qd or bid tapinarof cream: 1% qd tapinarof cream: 1% qd vehicle cream: qd pk sampling weeks 1, 2, 4, 8, and 12 days 1, 15, and 29 weeks 4 and 12 ad, atopic dermatitis; bid, twice daily; bsa, body surface area; iga, investigator global assessment; pga, physician global assessment; pk, pharmacokinetic; qd, once daily. pharmacokinetic sampling and exposure parameters ■ tapinarof plasma concentrations were measured using a highly sensitive assay that permitted assessment of drug levels to picogram (pg [10-12 g])/ml level – the lower limit of quantitation (lloq) was 50 pg/ml in the psoriasis trials and 40 pg/ml in the ad trial ■ because most samples were below the lloq (blq), the exposure–response analysis used imputed concentration values for blq samples that assumed an exposure level of approximately half of the lloq ■ pk parameters were the minimum and maximum plasma concentrations (c min and c max ) of tapinarof endpoints and statistical analysis ■ tapinarof plasma concentrations were evaluated for relationships with disease (ad or plaque psoriasis), tapinarof dose (0.5% or 1%), and application frequency (qd or twice daily [bid]) ■ a separate analysis of the maximal-use trial in psoriasis investigated whether tapinarof exposure correlated with percentage bsa affected at baseline ■ to investigate any relationship between tapinarof exposure and safety endpoints, tapinarof exposure (c min and c max ) was categorized as follows: – ‘0’ (patients randomized to vehicle) – ‘≤blq’ (patients with undetectable tapinarof exposure) – ‘>blq’ (patients with measurable tapinarof concentrations) – the >blq group was then grouped into tertiles of exposure ■ safety assessments included adverse events of special interest (aesis): folliculitis, contact dermatitis, and headache ■ efficacy assessments in patients with psoriasis included physician global assessment (pga) scores on day 29 and change from baseline in psoriasis area and severity index (pasi) scores on day 29 ■ the relationship between tapinarof exposure and efficacy was not assessed in patients with ad ■ demographics and pk concentrations were assessed in patients who received ≥1 dose of trial drug and had ≥1 pk sample (pk population) ■ efficacy–response analyses were assessed in all patients who received ≥1 dose of trial drug (safety population) results patient baseline characteristics ■ the majority of patients (58.9% [346/587]) had plaque psoriasis; 53.8% overall were male; and the mean age was 41.8 years (table 2) ■ overall, 67.8% (398/587) of patients received tapinarof and 32.2% (189/587) received vehicle – among patients in the tapinarof groups, most (69.8%) received tapinarof 1% qd; the remainder received tapinarof 0.5% qd (9.8%), 0.5% bid (10.3%), or 1% bid (10.1%) table 2. baseline patient demographics (pk population) patients with ad patients with plaque psoriasis overall (n=587)phase 2b trial (n=241)5 phase 2a maximal-use trial (n=21)4 pivotal phase 3 trials2 psoaring 1 (n=139) psoaring 2 (n=186) age, years, mean (sd) 29.5 (14.9) 51.8 (13.9) 47.9 (13.4) 52.1 (12.4) 41.8 (17.2) male, n (%) 122 (50.6) 13 (61.9) 70 (50.4) 111 (59.7) 316 (53.8) weight, kg, mean (sd) 76.8 (24.0) 97.5 (24.6) 94.1 (25.2) 93.0 (23.1) 86.8 (25.4) bmi, kg/m2, mean (sd) 27.5 (7.6) 33.1 (7.9) 32.2 (8.5) 31.8 (7.4) 30.1 (8.1) ad, atopic dermatitis; bmi, body mass index; pk, pharmacokinetic; sd, standard deviation. pharmacokinetics of tapinarof ■ tapinarof plasma exposure was low overall and below quantifiable limits in the majority (62.6% [1243/1985]) of samples using a highly sensitive assay ■ mean (sd) c min and c max were 27.6 (23.3) pg/ml and 340 (6270) pg/ml, respectively ■ there were no trends observed between tapinarof plasma concentrations and disease (ad or psoriasis), or the concentration of tapinarof cream (0.5%, 1%), or frequency (qd, bid) of application (figure 1) ■ in a separate, post hoc analysis of the psoriasis maximal-use trial, there was also no correlation between tapinarof plasma concentration and bsa in patients with psoriasis (ranging from 21%–46%) (figure 2) ■ in the maximal-use trial in patients with psoriasis, tapinarof plasma exposure declined over time, and was approximately 10-fold lower on day 29 than on day 14 figure 1. tapinarof plasma concentrations over time remained low in ad and psoriasis trials, regardless of dose or application frequency *horizontal lines indicate the lloq for the assays used in the psoriasis trials (50 pg/ml) and the ad trial (40 pg/ml). dashed lines indicate median trend lines. ad, atopic dermatitis; bid, twice daily; lloq, lower limit of quantitation; qd, once daily. figure 2. no correlation between tapinarof exposure (c max on days 1 and 29) and baseline %bsa affected in the psoriasis maximal-use trial bsa, body surface area; c max maximum plasma concentration. exposure–response analyses ■ in the phase 2a maximal-use trial, there was no relationship between tapinarof plasma exposure and efficacy in patients with psoriasis, including improvements in pga score and change from baseline in pasi score ■ there was no relationship between tapinarof exposure and aesis of folliculitis, contact dermatitis, or headache in patients with ad or psoriasis across all trials ■ there was no correlation between tapinarof plasma exposure and pasi response on day 29 (figure 3) figure 3. no correlation between tapinarof exposure (c max on day 29) and change in pasi score in psoriasis maximal-use trial c max maximum plasma concentration; pasi, psoriasis area and severity index. conclusions ■ tapinarof cream 1% qd is efficacious and well tolerated, including on intertriginous and sensitive skin areas, in patients with mild to severe plaque psoriasis ■ topical application of tapinarof cream 1% qd in patients with psoriasis or ad resulted in minimal systemic exposure ■ the maximal-use trial in psoriasis demonstrated that tapinarof plasma exposure declined over time ■ furthermore, tapinarof systemic exposure was also unrelated to %bsa affected for patients with psoriasis ■ this exposure–response analysis demonstrates a lack of dependence on systemic activity for the therapeutic efficacy of tapinarof cream references 1. dermavant sciences. vtama (tapinarof) cream, 1%: us prescribing information. 2022. https:// www.vtama.com/docs/dmvt_vtama_pi.pdf. accessed july 2022. 2. lebwohl mg, et al. n engl j med. 2021;385:2219–2229. 3. strober b, et al. j am acad dermatol. 2022. https://doi.org/10.1016/j. jaad.2022.06.1171. 4. jett je, et al. am j clin dermatol. 2022;23(1):83–91. 5. peppers j, et al. j am acad dermatol. 2019;80(1):89–98. acknowledgments this trial was funded by dermavant sciences, inc. the authors thank the participating investigators, patients and their families, and colleagues involved in the conduct of the trial. j.d.r. serves as a consultant/ advisor and clinical research investigator for dermavant sciences, inc. s.g. is a speaker for abbvie, aclaris, janssen, pfizer, and sun pharma. h.c.h. has received consultancy fees, honorarium, and speaker fees from dermavant sciences, inc. j.e.j., p.m.b., d.s.r., and s.c.p. are employees of dermavant science, inc. with stock options. editorial and medical writing support under the guidance of the authors was provided by apothecom, uk, and was funded by dermavant sciences, inc. in accordance with good publication practice (gpp3) guidelines (ann intern med. 2015;163:461–464). contact dr del rosso at jqdelrosso@yahoo.com with questions or comments. 1 20 25 30 35 40 45 50 10 100 10,000 1,000 t ap in ar o f p la sm a c m ax ( p g /m l) %bsa affected at baseline c max on day 1 (individual patients) c max on day 29 (individual patients) 1000 200 300 400 500 -20 -40 0 20 40 c h an g e fr o m b as el in e p a s i s co re tapinarof plasma c max (pg/ml) c max on day 29 (individual patients) 0 5 25201510 1% qd 100 1,000 t ap in ar o f c o n ce n tr at io n (p g /m l, lo g s ca le ) time (hours) 0.5% qd lloq 1% bid 0.5% bid tapinarof dose and application frequency patient population and trials n –– 1% qd psoriasis phase 2a maximal-use trial psoaring 1 trial psoaring 2 trial 278 ad phase 2b trial –– 1% bid ad phase 2b trial 40 –– 0.5% qd ad phase 2b trial 39 –– 0.5% bid ad phase 2b trial 41 exposure–response analysis demonstrates response to tapinarof is driven by local effects at sites of application james del rosso,1 scott guenthner,2 h. chih-ho hong,3 john e. jett,4 philip m. brown,4 david s. rubenstein,4 stephen c. piscitelli4 1jdr dermatology research/thomas dermatology, las vegas, nv, usa; 2the indiana clinical trials center, plainfield, in, usa; 3university of british columbia and probity medical research, surrey, bc, canada; 4dermavant sciences inc., morrisville, nc, usa skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 302 compelling comments christina m. jenkins: weaving the history of artificial hair extensions john tsatalis, ba,1 brandon burroway, mba,1 jacob griggs, ba1 1university of miami miller school of medicine, department of dermatology and cutaneous surgery, miami, fl the desire to have a full head of hair or wear a different hairstyle is not unique to the 21st century. in ancient egypt and rome wigs were important social markers of attractiveness, health, and standing. evidence also demonstrates that in addition to wigs, primitive sewn-in weaves were worn in ancient egypt (ca. 1300 bc),1 suggesting our ancient counterparts similarly valued keeping their hairpieces in place. in 1952, an african american woman named christina jenkins solved this millennium old problem with the invention of “hairweeve”. after working for a wig manufacturer, jenkins patented “a method and apparatus by which commercial human hair [could] be securely attached to the live hair on the head” (figure 1).2,3 by sewing hair weaves into braided hair on the scalp, jenkins invented the modern weave. given the demand for her invention, jenkins opened a “hair-weev” academy and spent the next 50 years training cosmetologists from across the world.3 in the 1980s, 1990s, and 2000s the popularity of weaves exploded as prominent black women like janet jackson, lisa bonet, naomi campbell, and tyra banks embraced artificial hair extensions. as weaves were brought into the mainstream, they helped initiate an ongoing national discourse on hegemonically defined beauty standards and cultural authenticity, with oprah winfrey outspokenly advocating for natural hairstyles. today, enhancements like bonding, singeing, and access to hair of different color and texture have created more natural appearing products, while the well-publicized risk of central centrifugal cicatricial alopecia has created a movement toward improved safety profiles for hair weaves. as jenkins’ invention adapts to modern values and demands, including a newfound appeal toward male users, the weave will assuredly continue to play an important role in hair. figure 1. “permanently attaching commercial hair to live hair” patent illustration filed by christina m. jenkins, may 4, 1951. skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 303 conflict of interest disclosures: none funding: none corresponding author: john tsatalis dr. phillip frost department of dermatology and cutaneous surgery university of miami miller school of medicine 1475 nw 12th ave., suite 2175, miami, fl 33136 phone: 305-243-4472 fax: 305-243-6191 email: jtsatalis@med.miami.edu references: 1. kemp b. “tell el-amarna, 2014.”. the journal of egyptian archaeology. 2014;100:1-33. 2. jenkins c, inventor. permanently attaching commercial hair to live hair. us patent 26216631952. 3. family j. genealogy tracers obituaries and memorial programs. allen county public library genealogy center published 2003. accessed. mailto:jtsatalis@med.miami.edu acknowledgements: medical writing support was provided by prescott medical communications group (chicago, il) with financial support from ortho dermatologics | presented at the fall clinical dermatology conference • october 17-20, 2019 • las vegas, nv synopsis ◾ acne is a common problem among asian adolescents and adults1,2 ◾ generally, asian skin is more pigmented, with a higher risk of acne sequelae3,4 ◾ potential for skin irritation and dryness, along with pigmentary changes, are key concerns that can significantly affect compliance and quality of life (qol)1,5 ◾ the first lotion formulation of tretinoin (altreno® ortho dermatologics, bridgewater, nj) was developed by utilizing novel polymeric emulsion technology to provide an important alternative option to treat acne patients who may be sensitive to the irritant effects of other tretinoin formulations6 objective ◾ data from two phase 3 studies (nct02932306, nct02965456) were analyzed post hoc to evaluate the efficacy, tolerability, and safety of tretinoin 0.05% lotion in asian patients with moderate-to-severe acne methods ◾ data from asian participants in two phase 3 studies were pooled and analyzed ◾ participants in both studies were randomized (1:1) to tretinoin 0.05% lotion or vehicle, once-daily for 12 weeks • in these studies, cerave® hydrating cleanser and cerave® moisturizing lotion (l’oreal, ny) were provided as needed for optimal moisturization/cleaning of the skin ◾ efficacy assessments included: • percent changes from baseline in inflammatory and noninflammatory lesions • treatment success, defined as a ≥2-grade reduction from baseline in evaluator’s global severity score (egss) with a final grade of 0 (clear) or 1 (almost clear) ◾ qol was assessed using the validated acne-specific quality of life (acne-qol) scale ◾ safety, adverse events (aes), cutaneous tolerability and hyperor hypo-pigmentation (range, 0 [none] to 3 [severe]) were also evaluated novel tretinoin 0.05% lotion for the once-daily treatment of moderate-to-severe acne vulgaris in an asian population george han, md, phd1; april w. armstrong, md, mph2; seemal r. desai, md3,4; eric guenin, pharmd, phd, mph5 1icahn school of medicine at mount sinai, new york, ny; 2keck school of medicine at university of southern california, los angeles, ca; 3innovative dermatology, pa, plano, tx; 4the university of texas southwestern medical center, dallas, tx; 5ortho dermatologics, bridgewater, nj figure 1. percent reduction in lesion counts a. inflammatory lesions -80% -60% -40% -20% 0% baseline week 4 week 8 week 12 ls m e a n p e rc e n t r e d u ct io n -59% -44% -35% -22% -24% -42% tretinoin 0.05% lotion (n=36) vehicle (n=33) b. noninflammatory lesions -25% -7% -35% -9% -51% -24% -80% -60% -40% -20% 0% baseline week 4 week 8 week 12 ls m e a n p e rc e n t r e d u ct io n tretinoin 0.05% lotion (n=36) vehicle (n=33) *p=0.012 vs vehicle. multiple imputation method used for missing values. ls, least squares. figure 2. treatment successa 0% 10% 20% 30% 40% 1% 5% week 4 7% 2% week 8 27% 17% week 12 tretinoin 0.05% lotion (n=35) vehicle (n=33) p e rc e n ta g e o f a si a n p a rt ic ip a n ts adefined as ≥2-grade reduction from baseline in evaluator’s global severity score with a final grade of 0 (clear) or 1 (almost clear). multiple imputation method used for missing values. figure 3. quality of life 0 1 2 3 4 5 6 7 8 9 10 self-perception role-emotional role-social acne symptoms m e a n a b so lu te c h a n g e f ro m b a se lin e 5.9% 2.9% 2831 3.4% 1.5% 2831 6.5% 3.1% 2832 8.2% 4.4% 2832n= tretinoin 0.05% lotion vehicle *p<0.05; **p<0.01; ***p≤0.001 vs vehicle. no imputation for missing values. safety ◾ only five asian participants in the pooled population reported any aes with tretinoin 0.05% lotion (table 2) ◾ all of these aes with tretinoin 0.05% were mild or moderate and transient, and none were considered serious or related to treatment ◾ there were slight transient increases in scaling and burning over the first 4-8 weeks (figure 4) ◾ mild hyperpigmentation was reported at baseline (mean score 0.8) and remained mild throughout the study figure 4. cutaneous safety and tolerability assessments baseline week 4 week 8 week 12 m e a n s co re s 0 1 2 3 0 1 2 3 baseline week 4 week 8 week 12 itching burning stinging itching (vehicle) burning (vehicle) stinging (vehicle) scaling erythema scaling (vehicle) erythema (vehicle) score range 0-3 with 0=none and 1=mild. results participants ◾ the pooled intent-to-treat analysis included 69 asian participants, 42 (60.9%) of whom were female (table 1) • ages in this subpopulation ranged from 12 to 48 years • based on egss scores, all participants had moderate or severe acne before treatment; the proportion of severe in asian participants (18.8%) was higher than in the general study population (11.0%)6 table 1. demographics and baseline characteristics tretinoin 0.05% (n=36) vehicle (n=33) total (n=69) age, years mean (sd) 20.7 (7.9) 21.1 (6.9) 20.9 (7.4) range 12-38 12-48 12-48 sex, n (%) female 18 (50.0) 24 (72.7) 42 (60.9) egss score, n (%) 3 moderate 28 (77.8) 28 (84.8) 56 (81.2) 4 severe 8 (22.2) 5 (15.2) 13 (18.8) lesion count, mean (sd) inflammatory 28.4 (6.4) 26.0 (4.8) 27.2 (5.8) noninflammatory 44.9 (21.3) 43.7 (20.8) 44.4 (20.4) egss, evaluator’s global severity score; sd, standard deviation. efficacy ◾ at week 12, mean percent reductions in inflammatory and noninflammatory lesion counts were greater with tretinoin 0.05% vs vehicle (figure 1) ◾ treatment success at week 12 was also greater with tretinoin 0.05% vs vehicle (figure 2) ◾ for each acne-qol domain, mean score improvements from baseline were significantly greater with tretinoin 0.05% compared to vehicle (figure 3) table 2. adverse events summary of aes, n (%) tretinoin 0.05% (n=34) vehicle (n=31) any aes 5 (14.7) 6 (19.4) any serious aes 0 0 any aes leading to discontinuation 0 0 deaths 0 0 severity of aes, n (%) mild 3 (8.8) 5 (16.1) moderate 2 (5.9) 1 (3.2) severe 0 0 relationship to study drug, n (%) related 0 1 (3.2) unrelated 5 (14.7) 5 (16.1) treatment-related aesa application site exfoliation 0 1 (3.2) areported in any participants in either treatment arm. conclusions ◾ data pooled from two phase 3 studies showed that in asian participants (n=69), tretinoin 0.05% lotion was significantly more effective than vehicle in reducing noninflammatory acne lesions and improving qol ◾ this novel lotion formulation was well-tolerated, with no treatment-related aes and no concerns with skin dryness, irritation or hyperpigmentation references 1. see ja, et al. j dermatol. 2018;45(5):522-528. 2. perkins ac, et al. j eur acad dermatol venereol. 2011;25(9):1054–1060. 3. aramaki j, et al. br j dermatol. 2002;146(6):1052–1056. 4. muizzuddin n, et al. j dermatol sci. 2010;59(2):123–128. 5. abad-casintahan f, et al. j dermatol. 2016;43(7):826–828. 6. tyring sk, et al. j drugs dermatol. 2018;17(10):1084-1091. author disclosures dr. george han has nothing to disclose. dr. april armstrong has served as a research investigator and/or consultant for abbvie, janssen, leo, novartis, ucb, ortho dermatologics, dermira, sanofi, regeneron, bms, dermavant, and modernizing medicine. dr. seemal desai has served as a research investigator and/or consultant for skinmedica, ortho dermatologics, galderma, pfizer, dermavant, almirall, dermira, and watson. dr. eric guenin is an employee of ortho dermatologics. efficacy of incobotulinumtoxina (xeomin®) for the treatment of glabellar frown lines in male subjects: post-hoc analyses from randomized, double-blind pivotal studies derek h jones, md1; martina kerscher, md2; thorin geister, phd3; michael a hast, phd4; petra weissenberger, md3 1skin and laser physicians of beverly hills; beverly hills, ca, usa; 2division of cosmetic science, university of hamburg; hamburg, germany; 3merz pharmaceuticals gmbh, frankfurt am main, germany; 4merz north america, inc.; raleigh, nc, usa • compared with females, males demonstrate lower response rates on gfl wrinkle severity scales (fws, mas) when treated with the fda-recommended 20 u of incobotulinumtoxina (figures 2 and 3) results were highly consistent between the pooled pivotal phase 3 us studies on gfls and the european pivotal phase 3 ufl study • a high proportion of both male and female subjects in the incobotulinumtoxina post-hoc analyses achieved ≥1-point improvements from baseline at maximum contraction (figures 2 and 3) • moreover, high proportions of both male and female subjects receiving incobotulinumtoxina in the pooled phase 3 gfl studies demonstrated a ≥1-point improvement at rest (figures 2 and 3) a 1-point improvement at rest is an important indicator that subjects received an aesthetic benefit that is observable during typical “real-world” circumstances (ie, without having to fully contract their muscles) • interest among men in minimally invasive cosmetic procedures continues to increase disclosure: this study was sponsored by merz north america, inc. subjects and treatment • previously described pooled, post-hoc analysis of incobotulinumtoxina pivotal phase 3 gfl studies in the us3 was extended to include a male subgroup analysis n=55 males (incobotulinumtoxina, n=34; placebo, n=21) with moderate to severe gfls at baseline (facial wrinkle scale [fws]) • supportive data are also provided from a post-hoc analysis of the european phase 3 study on incobotulinumtoxina for upper facial lines (ufls), including the glabellar area4 n=21 males (incobotulinumtoxina, n=11; placebo, n=10) with moderate to severe gfls at baseline (merz aesthetics scales [mas]) • 20 u of incobotulinumtoxina (4 u in 0.1 cc in each of 5 injection sites in the gfl) were administered to each subject subjects in the ufls study also received treatment for horizontal forehead lines and crow’s feet; post-hoc analyses were not conducted for these treatment areas endpoints • pivotal phase 3 us glf studies: pooled post-hoc analysis % of subjects with a score of 0 or 1 on the fws at maximum contraction at 30 days (investigator-assessed) % of subjects with a ≥1-point change on the fws at maximum contraction at 30 days (investigator-assessed) % of subjects with a ≥1-point change on a separate 4-point scale at rest (subject-assessed) subjects’ 4-point rating scale ranged from 0 (no muscle action possible) to 3 (strongest muscle action possible) • pivotal phase 3 eu study on upper facial lines: post-hoc analysis % of subjects with a score of 0 or 1 on mas (gfls only) at maximum contraction at 30 days (investigator-assessed) % of subjects with a ≥1-point reduction on the mas (gfls only) at maximum contraction at 30 days (investigator-assessed) • compared with females, males demonstrate lower response rates on wrinkle severity scales in studies on all 3 available botulinum toxins • variations in treatment response are potentially associated with key male anatomic differences (eg, muscle mass) • overall, results emphasize the importance of customized treatment plans figure 2. incobotulinumtoxina pooled analysis* of phase 3 gfl studies: responder analysis at 30 days figure 3. incobotulinumtoxina phase 3 upper facial lines study*: gfl responder analysis at 30 days figure 4. incobotulinumtoxina and onabotulinumtoxina pivotal phase 3 gfl studies: gfl responder analysis at 30 days 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% *n=547 total subjects in pooled analysis (incobotulinumtoxina, n=366; placebo, n=181) males: incobotulinumtoxina, n=34; placebo, n=21 m al es fe m al es fu ll c oh or t m al es fe m al es fu ll c oh or t m al es fe m al es fu ll c oh or t 56% 81% 78% 79% 87% 86% 65% 75% 73% re sp on d er s, % investigator-assessed responders at maximum contraction (score of 0 or 1 on fws) ≥ 1-point change on fws at maximum contraction (investigator-assessed) ≥ 1-point change on 4-point scale at rest (subject-assessed) conclusions references: 1. american society for aesthetic plastic surgery. procedural statistics. http://www.surgery.org/media/statistics. accessed: march 30, 2017; 2. keaney tc, alster ts. dermatol surg. 2013;39(10):1434-1443; 3. jones d, carruthers j, narins rs, et al. dermatol surg. 2014;40(7):776-785; 4. kerscher m, et al. dermatol surg. 2015;41(10):1149-1157; 5. botox [package insert]. irivine, ca: allergan, inc.; 2016; 6. brandt f, et al. dermatol surg. 2009;35(12):1893-1901; 7. monheit g, et al. j drugs dermatol. 2012;11(9):1041-1045; 8. keaney tc, alster ts. dermatol surg. 2013;39(10):1434-1443; 9. sattler g, et al. dermatol surg. 2010;36 suppl 4:2146-2154; 10. kane ma, et al. dermatol surg. 2015;41(11):1310-1319. discussion key differences in male facial anatomy • males have a greater muscle mass in the glabellar area (procerus and corrugators supercilii) compared with females7 • difference in muscle mass is likely a key factor in determining males’ threshold for response to botulinum toxin treatment7 • male facial anatomy also varies with respect to skull shape/bony prominences and vascularization8 best practices • gender-specific differences in treatment response provide an opportunity to revisit best practices for botulinum toxin administration and treatment plan development • the most important factor in achieving the best possible outcomes is the development of a customized aesthetic treatment plan careful evaluation of the patient’s aesthetic concerns both at rest and during animation is particularly important for achieving natural-looking results the final individualized treatment plan should be developed collaboratively with the patient and account for all variables that may affect aesthetic outcomes, including gender, age, ethnicity, skin quality, baseline wrinkle severity, muscle mass, and individual patient expectations • proper reconstitution technique is critical to avoid under-dosing the patient in the case of incobotulinumtoxina, gentle inversion and swirling of the vial is required to ensure the full contents of the vial are properly suspended in the diluent study limitations • overall, the number of male subjects available for post-hoc analyses was small • available active comparator studies for incobotulinumtoxina and onabotulinumtoxina for gfls enrolled no male subjects,9,10 thus preventing their inclusion in these subgroup analyses however, the proportions of male responders to incobotulinumtoxina on the fws and mas were consistent between studies, and similar trends have been observed individually for other botulinum toxins5,6 • the proportions of males who were considered responders (ie, score of 0 or 1 on respective wrinkle severity scales) were similar between incobotulinumtoxina and onabotulinumtoxina5 at 30 days at the same 20 u dose (figure 4) • similar differences between male and female subjects were also observed in the pivotal phase 3 study for abobotulinumtoxina (dysport) in the treatment of gfls6 however, variations in study design and the lack of a well-defined dose conversion between abobotulinumtoxina and other botulinum toxin formulations preclude a direct comparison of results 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% *n=156 total subjects in ufl study (incobotulinumtoxina, n=105; placebo, n=51) males: incobotulinumtoxina, n=11; placebo, n=10 m al es fe m al es fu ll c oh or t m al es fe m al es fu ll c oh or t 55% 84% 83% 82% 97% 95% re sp on d er s, % investigator response at maximum contraction, gfls (score of 0 or 1 on mas) ≥ 1-point change on mas at maximum contraction (investigator-assessed) • despite the increasing number of men seeking aesthetic procedures, they are underrepresented in the literature on aesthetic products such as botulinum toxins a previous analysis of 17 studies on botulinum toxins in aesthetic indications showed that only ~11% of subjects in these trials were male2 • therefore, there remains a clinical need for studies that address how men and women respond differentially to aesthetic treatments to support individualization of treatment plans • the objective of this analysis was to assess the efficacy of incobotulinumtoxina (xeomin(r); merz pharmaceuticals gmbh, frankfurt, germany) for the treatment of glabellar frown lines (gfls) in men figure 1. minimally invasive cosmetic procedures in men. in 2016, men accounted for ~9% of all minimally cosmetic procedures.1 the number of botulinum toxin injections among men increased 50% from 2006 to 2016.1 xeomin® is a registered trademark of merz pharma gmbh & co kgaa. background and objective methods results 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 71 males received onabotulinumtoxina in combined trials5 34 males in pooled analysis received incobotulinumtoxina m al es fe m al es fu ll c oh or t m al es fe m al es fu ll c oh or t 56% 81% incobotulinumtoxina onabotulinumtoxina5 78% 59% 85% 80% re sp on d er s, % investigator-assessed responders at maximum contraction, (score of 0 or 1 on fws) investigtaor response, gfl (score of 0 or 1 on 4-point scale) fe m al es statistics from cosmetic surgery national data bank statistics, american society for aesthetic plastic surgery men 9% women 91% 9% of injectables treatments men report an overall desire to “maintain” their appearance using cosmetic procedures >1 million procedures overall in 2016 botulinim toxin injections minimally invasive figures caha and ha injections 20 16 v s 20 0 6 50% 40% 230% fc17postermerzjonesefficacyincobotulinumtoxina.pdf adalimumab for nail psoriasis: efficacy and safety from the open-label extension of a phase-3, randomized, placebo-controlled trial alice b gottlieb1, boni e elewski2, martin m okun3, jerry bagel4, yves poulin5, yihua gu6, ziqian geng6, david a williams6, wendell c valdecantos6 1 new york medical college, valhalla, ny, usa; 2university of alabama at birmingham, school of medicine, birmingham, al, usa; 3fort healthcare, fort atkinson, wi, usa; 4university medical center of princeton at plainsboro, plainsboro, nj, usa; 5centre dermatologique du québec métropolitain, québec, qc, canada; 6abbvie inc, north chicago, il, usa introduction presented at the fall clinical dermatology conference 36th anniversary • las vega, nevada • october 12 – 15, 2017 methods results • treatments that are simultaneously effective in nail and skin psoriasis are needed as affected patients have worse quality of life and pain than patients with skin psoriasis alone. • management of nail psoriasis is challenging; the disease etiology and pathology are not fully understood and treatment guidelines are limited.1,2 topical agents have been minimally effective, but improvement in nail psoriasis has been reported following treatment of skin psoriasis with biologic therapies.3 • we evaluated the safety and efficacy of originator adalimumab (abbvie) for fingernail psoriasis in the open-label-extension period (period b) of a phase-3 trial of adalimumab (ada) in patients with moderate-to-severe psoriasis who also had substantial, clinically impactful, moderate-to-severe fingernail psoriasis (clinicaltrials.gov nct 02016482). 1. crowley jj, et al. jama dermatol. 2015;151:87-94. 2. langley rg, et al. j eur acad dermatol venereol. 2012;26:373-81. 3. pasch mc. drugs. 2016;76:675-705. 4. cassell se, et al. j rheum. 2007;34:1239. 5. rich p, et al. j am acad dermatol. 2003;49:206-12. references • for psoriasis patients with concomitant nail disease who received 40 mg ada every-other-week treatment for 26 weeks in period a, treatment response was maintained from entry to period b through week 52. • patients receiving pbo in period a, who switched to 40 mg ada every-other-week treatment in period b, eventually reached a similar response at week 52, to those receiving continuous ada treatment. • no new safety risks were identified with 40 mg ada every-otherweek treatment for 52 weeks. conclusions a gottlieb received fees for serving on advisory boards and for consulting services from amgen inc.; astellas, akros, centocor (janssen), inc.; celgene corp., bristol myers squibb co., beiersdorf, inc., abbott labs. (abbvie), teva, actelion, ucb, novo nordisk, novartis, dermipsor ltd., incyte, pfizer, canfite, lilly, coronado, vertex, karyopharm, csl behring biotherapies for life, glaxo smith kline, xenoport, catabasis, meiji seika pharma co., ltd, takeda, mitsubishi,tanabe pharma development america, inc, genentech, baxalta, kineta one, kpi therapeutics, crescendo bioscience, aclaris, amicus, reddy labs, valeant, dermira, allergan. be elewski received research funding for clinical research support, paid to her affiliation, from abbvie, amgen, boehringer ingelheim, celgene, incyte, lilly, merck, novan, novartis, pfizer, valeant, and viamet; received honoraria for consultant services from anacor, celgene, lilly, novartis, pfizer, and valeant. mm okun received honoraria from abbvie for advisory board participation and speaker services, and from abbvie, gilead science, and crescendo biosciences for consultant services. dr. okun was an abbvie employee during this study and is currently affiliated with fort healthcare, fort atkinson, wi, usa. j bagel received honoraria or grants for speaker, consultant, or investigator services with abbvie, boehringer ingelheim, celgene, eli-lilly, janssen, leo pharma, novartis, and sun valiant. y poulin received grants for investigator services with abbvie, amgen, baxalta, celgene, centocor, janssen, eli lilly, glaxo smith kline, incyte, leo pharma, merck, novartis, pfizer, and ucb pharma, and received honoraria for speaker and/ or advisory board services for abbvie, amgen, janssen, and leo pharma. y gu, z geng, d williams, w valdecantos receive a salary as abbvie employees, and may also receive abbvie stocks or stock options. abbvie inc. funded this study and participated in the study design; study research; collection, analysis and interpretation of data; and writing, reviewing and approving of this publication. all authors had access to the data, and participated in the development, review, and approval, and in the decision to submit this publication. the authors would like to acknowledge jody bennett, employed by abbvie, for medical writing support in the production of this publication. disclosures & acknowledgements • patients with chronic, moderate-to-severe plaque psoriasis and fingernail psoriasis were enrolled. in 26-week period a, patients were randomized 1:1 to 40 mg ada every-other-week (adaeow) after initial 80 mg dose, or matching placebo (pbo). • from week 16, if the affected body surface area increased by ≥25% from baseline, patients were required to roll over to the 26-week period b (early escape). patients completing period a at week 26 or who escaped early, entered period b at week 26. • at period b entry (week 26), patients receiving pbo in period a received an initial blinded dose of 80 mg ada; patients receiving ada in period a received matching pbo. all received 40 mg adaeow from weeks 27 through 51 (figure 1). figure 1. study design ada 40 mg eow pbo period a double-blind 26 weeks period b open-label extension (ole) 26 weeks screening 3-35 days week 0 a week 16 b week 26c week 52 1:1 randomiza�on ainitial dose of ada was 80 mg. bstarting at week 16, if psoriasis-affected bsa increased ≥25% over baseline, patients were rolled over to period b. cperiod-a ada arm received matching pbo; period-a pbo arm received blinded ada 80 mg. abbreviations: ada=adalimumab; eow=every-other-week dosing; pbo=placebo; bsa=body surface area. key inclusion criteria • adults diagnosed with both chronic, moderate-to-severe plaque psoriasis (with disease duration of at least 6 months) and moderateto-severe psoriasis in at least one fingernail (any disease duration). • bsa ≥10% and baseline target fingernail modified nail psoriasis severity index (mnapsi)4 ≥8; or bsa ≥5% with baseline target fingernail mnapsi ≥8 and baseline total mnapsi ≥20 (scale of total score 0 [no nail findings] to 130 [nail findings present in each nail]). • physician’s global assessment of fingernail (pga-f) of at least moderate severity for fingernail psoriasis (scale 0 [clear] to 4 [severe]). • nail psoriasis physical functioning severity (nppfs) score >3 (scale 0 [none] to 10 [severe]); or nail psoriasis pain numeric rating scale (nrs) score >3 (scale 0 [no pain] to 10 [severe pain]). endpoints • all efficacy variables assessed in period a were also assessed in period b (see list in table 3). period a primary and ranked secondary endpoints that were evaluated in period b are reported here. • two intent-to-treat (itt) patient populations were evaluated in period b: – overall itt_b population: all patients who received ≥1 study drug injection in period b. – early escape population: all patients who rolled over to period b after experiencing worsening of disease from baseline in period a. • period b treatment groups are identified by treatment received in period a/period b, ie, pbo/ada and ada/ada. • missing data were handled in period a by multiple imputation (mi), and in period b by non-responder imputation (nri) and by last observation carried forward (locf). safety • treatment-emergent adverse events (aes) in period b were analyzed for the itt_b population. • 217 patients were randomized in period a (108 to pbo; 109 to ada). – 94/108 (87.0%) pbo/ada and 94/109 (86.2%) ada/ada entered period b (table 1). – 81/94 (86.2%) pbo/ada and 87/94 (92.6%) ada/ada patients completed period b. table 1. patient disposition, period b disposition, n (%) pbo/ada, n=94 ada/ada, n=94 n % n % entered period b 94 100 94 100 completed period b 81 86.2 87 92.6 discontinued period b; primary reason: 13 13.8 7 7.4 adverse events 0 0 0 0 withdrew consent 1 1.1 1 1.1 lost to follow-up 2 2.1 0 lack of efficacy 6 6.4 4 4.3 all other reasonsa 4 4.3 2 2.1 aincludes requirement for alternate therapy, and other reasons. • demographic and baseline characteristics were generally comparable across the 2 treatment groups (table 2). patients showed substantial nail disease and pain at baseline. table 2. key demographics and baseline characteristics of patients entering period b characteristic pbo/ada, n=94 ada/ada, n=94 n % n % sex male 76 80.9 83 88.3 female 18 19.1 11 11.7 race white 90 95.7 89 94.7 asian 3 3.2 4 4.3 othera 1 1.1 1 1.1 bsa 5% to <10% 34 36.2 37 39.4 ≥10% 60 63.8 57 60.6 scalp psoriasis 80 85.1 80 85.1 psa 26 27.7 28 29.8 pga-f moderate 53 56.4 44 46.8 >moderate 41 43.6 50 53.2 pga-sb moderate 55 58.5 56 59.6 >moderate 39 41.5 37 39.4 mean sd mean sd age, years 47.1 11.44 47.3 11.82 bmi, kg/m2 (n=93) 29.2 6.88 (n=93) 29.6 5.09 duration of psoriasis, years 18.7 13.73 20.7 12.34 duration of nail psoriasis, years 12.0 11.12 12.4 9.65 pasi score 13.3 9.87 12.8 9.00 total fingernail mnapsi score (range 0-130) 58.6 20.78 57.0 18.34 total fingernail napsi score (range 0-80) 46.6 15.40 48.0 15.67 nail psoriasis pain (nrs) score (range 0-10) 5.7 2.25 5.0 2.48 b-snipi, scalp component (range 0-20) (n=16) 7.9 5.82 (n=23) 9.7 5.32 nppfs score (range 0-10) 5.2 2.15 5.2 2.63 dlqi score (range 0-30) (n=82) 12.3 6.73 (n=81) 13.0 7.31 nail psoriasis qol score (range 0-10) 5.2 2.28 4.9 2.79 aother includes black (ada/ada) and multi-race (pbo/ada). b1 patient had pga-s mild. for all scores listed above, higher scores indicate higher disease severity or impairment. abbreviations: pbo=placebo; ada=adalimumab; bsa=body surface area; psa=psoriatic arthritis; bmi=body mass index; pasi=psoriasis area severity index; pga=physician global assessment (-f=fingernail psoriasis, -s=skin psoriasis); napsi=nail psoriasis severity index (m=modified); nrs=numeric rating scale; b-snipi=brigham scalp nail inverse palmo-plantar psoriasis index; nppfs=nail psoriasis physical functioning severity; dlqi=dermatology life quality index; qol=quality of life. efficacy in period a • results at week 26 are shown in table 3. all results were statistically significant (p<0.001 for all but b-snipi 50 scalp and mnapsi=0; p<0.01). table 3. efficacy outcomes in period a pbon=108 ada, n=109 primary endpoint percent of patients who achieved at least a 75% reduction in total fingernail mnapsi (mnapsi 75) relative to baseline 3.4% 46.6% ranked secondary endpoints mean percent improvement from baseline in total fingernail napsi 11.5% 56.2% percent of patients who achieved total fingernail mnapsi=0 0% 6.6% mean improvement from baseline in nail psoriasis pain (nrs; used to capture a patient’s self-report of worst fingernail pain) 1.1 3.7 mean improvement from baseline in nppfs 0.8 3.7 percent of patients who achieved b-snipi 50 scalp (at least 50% improvement in the scalp component of the brigham scalp nail inverse palmo-plantar psoriasis composite index, among patients with a baseline scalp score of 6 or greater)a 0.4% 58.3% percent of patients who achieved pga-f 0 (clear) or 1 (minimal), with ≥2 grades improvement from baselineb 6.9% 48.9% ameasured only at us and puerto rico sites. bprimary endpoint in us only, for us regulatory purposes. abbreviations: pbo=placebo; ada=adalimumab; napsi=nail psoriasis severity index (m=modified); nrs=numerical rating score; nppfs=nail psoriasis physical functioning severity; pga-f=physician’s global assessment of fingernail. efficacy in period b (figure 2a-g) • overall itt_b population: at week 52, response rates for the various efficacy endpoints were maintained for patients who continued ada in period b, and improved for patients who switched from pbo in period a to ada in period b. • early escape population: – 188 patients were in the early escape population (94 pbo/ada; 94 ada/ada). – patients who experienced worsening of disease from baseline in period a and continued ada in period b had less improvement than those who switched from pbo in period a to ada in period b. – only 8 patients in the ada/ada group, vs. 56 in the pbo/ada group, experienced worsening of disease from baseline in period a and needed to escape early to period b. figure 2. efficacy outcomes in period b for two populations ≥ a. achievement of mnapsi 75 nri. missing at week 52 (n): itt_b 14 pbo/ada, 8 ada/ada; early escape 7 pbo/ada, 2 ada/ada. b. achievement of pga-f 0 or 1, with 2 grades improvement from baseline nri. missing at week 52 (n): itt_b 14 pbo/ada, 8 ada/ada; early escape 7 pbo/ada, 2 ada/ada. c. improvement from baseline in total fingernail napsi locf. d. achievement of total fingernail mnapsi 0 nri. missing at week 52 (n): itt_b 14 pbo/ada, 8 ada/ada; early escape 7 pbo/ada, 2 ada/ada. e. improvement from baseline in pain nrs locf. f. improvement from baseline in nppfs locf. itt_b population pbo/ada, n=94 ada/ada, n=94 early escape population pbo/ada, n=56 ada/ada, n=8 itt_b population pbo/ada, n=94 ada/ada, n=94 early escape population pbo/ada, n=56 ada/ada, n=8 itt_b population pbo/ada, n=94 ada/ada, n=94 early escape population pbo/ada, n=56 ada/ada, n=8 (period b entry); n=6 (week 52) itt_b population pbo/ada, n=94 ada/ada, n=94 early escape population pbo/ada, n=56 ada/ada, n=8 itt_b population pbo/ada, n=94 ada/ada, n=94 (period b entry); n=93 (week 52) early escape population pbo/ada, n=56 ada/ada, n=8 early escape population pbo/ada, n=56 ada/ada, n=8 itt_b population pbo/ada, n=94 ada/ada, n=94 (period b entry); n=93 (week 52) safety • approximately half of the patients experienced a treatment-emergent ae in period b (table 4). the rates of serious aes and serious infections were low. there were no aes of tuberculosis, malignancy, or aes leading to study-drug discontinuation; and no deaths. table 4. safety in period b adverse events (ae), n (%) period a period b pbo/ada n=108 ada/ada n=109 pbo/ada n=94 ada/ada n=94 any ae 61 (56.5) 64 (58.7) 44 (46.8) 47 (50.0) serious aes 5 (4.6) 8 (7.3) 3 (3.2) 3 (3.2) infections 30 (27.8) 32 (29.4) 25 (26.6) 30 (31.9) serious infectiona 2 (1.9) 4 (3.7) 2 (2.1) 1 (1.1) tuberculosis 0 0 0 0 malignancy 0 0 0 0 leading to study drug discontinuation 3 (2.8) 6 (5.5) 0 0 death 0 0 0 0 special interestb aes allergic reactionc 2 (1.9) 1 (0.9) 1 (1.1) 0 worsening/new onset of psoriasis 7 (6.5) 2 (1.8) 4 (4.3) 1 (1.1) injection-site reaction 3 (2.8) 4 (3.7) 2 (2.1) 2 (2.1) aserious infections: period a pneumonia (n=2 pbo), and bronchitis, diverticulitis, endocarditis, erysipelas (n=1 each ada); period b influenza (n=1 ada/ada), lung infection (n=1, pbo/ada), and diverticulitis (n=1, pbo/ ada). baes of special interest in <2 patients in a treatment group: period a oral candidiasis, congestive heart failure, intestinal perforation, and hematologic disorders including pancytopenia (ada); period b diverticulitis, myocardial infarction, and hematologic disorders including pancytopenia (pbo/ada). cincluded angioedema and anaphylaxis. abbreviations: pbo=placebo; ada=adalimumab. g. achievement of b-snipi 50 scalp nri. missing at week 52 (n): itt_b 3 pbo/ada, 2 ada/ada; early escape 3 pbo/ada, 1 ada/ada. itt_b population pbo/ada, n=9 ada/ada, n=16 early escape population pbo/ada, n=7 ada/ada, n=1 fc17posterabbviegottliebadalimumabnailpsoriasis.pdf skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 372 brief articles hypersensitivity reactions secondary to dupilumab in two patients with moderate to severe atopic dermatitis raina bembry, md1, navid malakouti, md1, mary maiberger, md1 1howard university hospital atopic dermatitis (ad) is a chronic inflammatory disease of the skin with a complex pathogenesis. it has both genetic and environmental factors leading to epidermal barrier defects and immune system derangements.1,2 ad occurs in nearly 15-30% of children and 2-10% of adults.2,3 conventional treatment for ad consists of emollients, topical corticosteroids, and topical calcineurin inhibitors. patients with moderate-to-severe ad not adequately managed by conventional therapies can be treated with cyclosporine, azathioprine, methotrexate, mycophenolate mofetil, and more recently, dupilumab.3 dupilumab is a human monoclonal igg4 antibody that inhibits the th-2 cytokines, interleukin-4 and interleukin13, by binding to the interleukin-4 receptor alpha subunit.4 dupilumab downregulates the expression of genes encoding inflammatory mediators and epidermal proliferation, and upregulates genes linked to epidermal barrier, lipid metabolism, and structure.4,5 injection site reactions are the most commonly reported adverse event associated with the use of dupilumab.7 hypersensitivity reactions to dupilumab are rare: less than 1% of trial patients reported having serum sickness, serum sickness-like, or urticarial reactions, which were not reported as adverse effects in phase 3 clinical trials.7,8 we present two cases of hypersensitivity reactions on second exposure to dupilumab in two adult-male case 1 a 68-year-old asian man with moderate-tosevere atopic dermatitis presented with worsening pruritus and pain, primarily of the hands, that negatively affected his quality of life. his disease was only partially managed with topical clobetasol ointment and oral methotrexate 12.5 mg, but he still required oral prednisone intermittently for flares. physical examination findings included introduction case presentation dupilumab is a human monoclonal igg4 antibody that is widely used to treat atopic dermatitis. dupilumab was recently fda approved to treat moderate to severe atopic dermatitis. here we decribe two cases of patients with moderate to severe atopic dermatitis who developed an acute hypersensitivity reaction within hours of their second dose of dupilumab. abstract skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 373 xerotic, lichenified, excoriated firm plaques on the hands, left foot, buttocks, and inguinal regions. additionally, hyperpigmentation and lichenification of the buttocks and inguinal region were noted. methotrexate was discontinued and he was injected with a 600 mg loading dose of dupilumab in clinic which was tolerated well. he reported improving pruritus on a oneweek telephone follow-up. within hours of his second injection, he developed a diffuse eruption and generalized pruritus. physical examination revealed scaly erythematous patches, plaques and papules involving the thighs, calves, feet, genitals, arms and elbows. the shave-biopsy of the right elbow performed at the time of the reaction showed spongiotic dermatitis with superficial, perivascular chronic inflammation, and rare eosinophils. the biopsy was consistent with a hypersensitivity reaction. dupilumab was discontinued and he was started on oral prednisone (1mg/kg) tapered over two weeks which improved the rash, but pruritus persisted. he was restarted on his previous dose of methotrexate which lead to moderate improvement in pruritus. case 2 a 53-year-old caucasian male presented with a 10-year history of recalcitrant atopic dermatitis. he had previously attempted and failed many treatments including the following: cyclosporine; mycophenolate mofetil; methotrexate; apremilast; narrowband uvb; high potency topical corticosteroids; topical calcineurin inhibitors; calcipotriene; and crisoborole. physical examination showed several erythematous papules coalescing into plaques on the upper extremities, lower extremities, and trunk, with eczematous patches on the face and scalp. there were eczematous, slightly erythematous to tan plaques on the bilateral lower legs and a thickened scaly plaque on the left elbow. he demonstrated clinical dermatographism with associated pruritus. the patient was initiated on dupilumab and tolerated the loading dose well. a scheduled maintenance dose two weeks later resulted in increased pruritus and worsening dermatitis within hours of injection. his physical examination showed eczematous dermatitis with lichenification, excoriations and fissures on his legs, back, and arms. there were erythematous, rough papules on the vertex scalp on a background of erythematous, hyperpigmented skin. dupilumab was discontinued and he was initiated on azathioprine, which lead to minor resolution of his pruritus and dermatitis. we described two cases of patients with moderate-to-severe atopic dermatitis (ad) who developed an acute hypersensitivity reaction within hours of their second dose of dupilumab. given the temporal relationship between the second dose of the dupilumab with the patient’s worsening dermatitis, and the skin biopsy consistent with a hypersensitivity reaction, we ascertain these hypersensitivity reactions were possibly a result of exposure to dupilumab. 9 we also conclude that the discontinuation of dupilumab and aggressive treatment with systemic and topical immunosuppressants returned both patients to baseline levels of their disease. it is unclear why the two patients experienced a hypersensitivity reaction from dupilumab. there is documentation of a non-specific inflammatory response after use of dupilumab, with resolution after cessation of the drug. 10 ad can be classified as either acute or chronic, intrinsic or extrinsic, and can even discussion skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 374 be differentiated by ethnicity. intrinsic ad affects 20% of the adult population, with normal levels of ige.5 in comparison to extrinsic, there is a higher immune system activation with increased levels of th-22 and th-17/il-23 in intrinsic ad.5 extrinsic ad affects 80% of the adult population and is associated with increased levels of ige and a predominance of th-2 activation.4,5 dupilumab targets cytokines in the extrinsic pathway, which may lead to a better response in patients with extrinsic ad. acute ad is characterized by an overactivation of th-2 and th-22 immune profiles, resulting in increased levels of il-4, il-13, il-31, and il-22.5 in chronic ad, there is a switch to a th-1 mediated pathway and a decrease in il-4 activity. the effective use of th-2 antagonists has resulted in new systemic therapies being investigated for the treatment of ad. the il13 antagonists, tralokinumab and lebrikizumab, il-31 antagonist, nemolizumab, and other th-2 antagonists are currently being evaluated.6 antagonists to ige, th-22, th-17/il-23, pde-4, tumor necrosis factor, and jak are also being evaluated for their effectiveness in the systemic treatment of ad.6 ad has a complex, multifactorial nature. the multitude of potential targets for pharmacologic intervention, as well as the variable response to common treatments warrants further investigation for the development of future pharmaceutical therapies. conflict of interest disclosures: none funding: none corresponding author: raina bembry, md howard university hospital department of dermatology 2041 georgia ave nw suite 4300 washington, dc 20060 email: raina.bembry@bison.howard.edu references: 1. refs eichenfield lf, tom wl, berger tg, et al. guidelines of care for the management of atopic dermatitis. journal of the american academy of dermatology. 2014;71(1):116-132. doi:10.1016/j.jaad.2014.03.023. 2. bieber t. atopic dermatitis. annals of dermatology. 2010;22(2):125. doi:10.5021/ad.2010.22.2.125. 3. sidbury r, davis dm, cohen de, et al. guidelines of care for the management of atopic dermatitis. journal of the american academy of dermatology. 2014;71(2):327-349. doi:10.1016/j.jaad.2014.03.030. 4. derme am, romanelli m, chiricozzi a. spotlight on dupilumab in the treatment of atopic dermatitis: design, development, and potential place in therapy. drug design, development and therapy. 2017;volume 11:1473-1480. doi:10.2147/dddt.s113192. 5. mansouri y, guttman-yassky e. immune pathways in atopic dermatitis, and definition of biomarkers through broad and targeted therapeutics. journal of clinical medicine. 2015;4(5):858-873. doi:10.3390/jcm4050858. 6. renert-yuval y, guttman-yassky e. systemic therapies in atopic dermatitis: the pipeline. clinics in dermatology. 2017;35(4):387-397. doi:10.1016/j.clindermatol.2017.03.012. 7. simpson el, bieber t, guttman-yassky e, et al. two phase 3 trials of dupilumab versus placebo in atopic dermatitis. new england journal of medicine. 2016;375(24):2335-2348. doi:10.1056/nejmoa1610020. 8. dupixent® (dupilumab) [package insert]. sanofi biotechnology (bridgewater, nj) and regeneron pharmaceuticals, inc. (tarrytown, ny) 9. zaki s. adverse drug reaction and causality assessment scales. lung india. 2011;28(2):152. doi:10.4103/0970-2113.80343. 10. davis jd, bansal a, hassman d, et al. evaluation of potential disease-mediated drug-drug interaction in patients with moderate-to-severe atopic dermatitis receiving dupilumab. clinical pharmacology & therapeutics. february 2018. doi:10.1002/cpt.1058. mailto:raina.bembry@bison.howard.edu poster presented at the winter clinical dermatology conference | kohala coast, hi | january 17-22, 2020 treatment patterns and depression and anxiety among patients newly identified with hyperhidrosis in a real-world database representing us commercial health plan members michael hull, ms1; kristin khalaf gillard, phd, pharmd2; jesse peterson-brandt, ms1; stephanie z. klein, md3 1optum life sciences, minneapolis, mn, usa; 2 dermira, inc., menlo park, ca, usa; 3university of utah hospital, salt lake city, ut, usa. introduction • hyperhidrosis is a condition characterized by excessive sweating and, frequently, concomitant social and emotional stress.1 hyperhidrosis affects an estimated one to five percent of individuals in the united states (us).1,2 • primary hyperhidrosis is idiopathic and often multi-focal, and results from over-activity of the sympathetic nerves; the most common affected area is the axillae, but other affected areas include the palms, soles, and craniofacial regions.2 another type of hyperhidrosis is secondary hyperhidrosis, which is attributable to underlying medical conditions or medications. • hyperhidrosis is associated with concomitant social and emotional stress due to limitations on health-related quality of life.4 the limited real-world observational data available in this population suggests that additional research is warranted. objective this study examined the patient characteristics, treatment patterns, and factors associated with concomitant depression and anxiety in patients newly treated with hyperhidrosis. methods patient selection • commercial health plan members with ≥2 hyperhidrosis diagnosis codes and/or antiperspirant prescription claims were identified from january 2010 through november 2017 from the optum research database, a de-identified research database that contains commercial and medicare advantage claims, containing both medical and pharmacy information from 1993 to current and covering over 60 million lives. – the index date was the first observed claim indicating hyperhidrosis. • patients had continuous enrollment with medical and pharmacy coverage for 12 months before (the baseline or pre-index period) and ≥12 months after the index date (the post-index, or follow-up period). • patients had no claims for related medical procedures (botulinum toxin a, microwave thermolysis, suction curettage, iontophoresis, or endoscopic thoracic sympathectomy) during the baseline period for codes indicating procedures specific to the treatment of hyperhidrosis, and no claims for these related medical procedures or pharmacy claims for oral systemic therapies within 7 days of the index date for codes indicating procedures or medications not specific to the treatment of hyperhidrosis. – oral systemic therapy included medications to control sweating such as anticholinergics, and specific calcium channel blockers and beta blockers. • a control cohort (cc) was identified of patients comparable to the hyperhidrosis cohort, but without evidence of hyperhidrosis. these patients were matched 1:1 on index year, age group, gender, and health plan region to a superset of patients with ≥1 indication of hyperhidrosis. – the index date for the cc patients was selected as a random date of health care resource utilization (hcru) during the identification period, such as an office visit, inpatient admission, or a prescription claim. – a uniform twelve-month follow-up period was used for the comparative analyses of the hyperhidrosis and control cohorts. – cc patients were followed for twelve months starting on the index date. they required continuous enrollment in their twelve-month preand post-index periods, as well as valid data in the fields of gender, age, and geographic region. outcomes • depression and/or anxiety were identified by ≥1 relevant diagnosis code or pharmacy claim. – depression was defined as ≥1 medical claim with a diagnosis code for depression in any position and/or ≥1 pharmacy claim for a medication indicated specifically as an antidepressant. a second indicator variable identified patients with new depression; i.e., depression that was not identified during the pre-index period. – anxiety was defined as ≥1 medical claim with a diagnosis code for anxiety in any position and/or ≥1 pharmacy claim for a medication indicated specifically as an anxiolytic. a second indicator variable identified patients with new anxiety; i.e., anxiety that was not identified during the pre-index period. – depression and/or anxiety was defined as above in the first year of follow-up and the total follow-up period while also including patients without a diagnosis code for depression or anxiety but with ≥1 pharmacy claim for a medication indicated for the treatment of both depression and anxiety. a second indicator variable identified patients with new depression or anxiety; i.e., depression or anxiety that was not identified during the pre-index period. • proportion of days covered (pdc) was defined as adherence for 1) prescription-strength antiperspirants and 2) oral systemic therapies. pdc was calculated for the first twelve months of the follow-up period. – the pdc represents the proportion of time over the course of a subject’s treatment that the patient was theoretically in possession of medication. – pdc was calculated by dividing the number of days on which medication was available based on filled prescriptions by the number of days between the earliest prescription claim in the observation period through the end of the observation period (i.e., twelve months of follow-up). analysis • all variables were analyzed descriptively. • a multivariable logistic regression model examined the presence of depression/anxiety on patient cohort while controlling for patient characteristics including gender, age, and geographic region, any post-index hyperhidrosis treatment, and five common comorbidities (respiratory infections, other lower respiratory infections, other upper respiratory infections, other gastrointestinal disorders, and other skin conditions) identified by the ahrq3 in this sample. results sample selection • a total of 44,484 patients with hyperhidrosis were identified (figure 1). • 58.5% were female, with mean (±sd) age 36.5±16.5 years. a total of 83.5% were ≥18 years old (figure 2). • for the cc cohort (n=137,451) 56.0% were female, with a mean (±sd) age 40.2±16.9 years (with 87.8% ≥18 years old). figure 1. sample selection ≥ 1 of the following: a prescription claim for an extraor prescription-strength antiperspirant or an icd-9 or icd-10 diagnosis code for hyperhidrosis in any position (n=309,709) continuous enrollment in the health plan with medical and pharmacy benefits for 12 months before the index date and ≥ 12 months beginning with the index date (n=143,876) at least one additional record or claim to confirm diagnosis of hyperhidrosis during the post-index period, and valid data for gender, age, and geographic region (n=47,570) no medical claims for botulinum toxin a, microwave thermolysis, suction curettage, iontophoresis, or endoscopic thoracic sympathectomy during the pre-index period for codes indicating procedures specific to the treatment of hyperhidrosis, or within 7 days before or after the index date for codes indicating procedures not specific to the treatment of hyperhidrosis (n=46,960) final sample no pharmacy claims for systemic therapies within 7 days before or after the index date (n=44,484) abbreviations: icd: international classification of disease figure 2. age distribution 0-8 9-17 18-24 25-34 35-44 45-54 55+ age group (years) 0.8 15.7 13.9 16.7 19.5 17.0 16.4 25 5 10 15 20 0 p er ce nt ag e of p at ie nt s patient characteristics • the most commonly occurring comorbid conditions (table 1) for the hyperhidrosis cohort as identified by the ahrq were respiratory infections (39.0%) and other skin disorders (30.9%). table 1. patient comorbidities ahrq comorbidities control cohort (n=137,451) hyperhidrosis cohort (n=44,484) p-value respiratory infections n 42,227 17,330 <0.001 % 30.72 38.96 other connective tissue disease n 33,509 12,745 <0.001 % 24.38 28.65 disorders of lipid metabolism n 29,148 8,929 <0.001 % 21.21 20.07 other skin disorders n 28,187 13,734 <0.001 % 20.51 30.87 hypertension n 27,769 8,220 <0.001 % 20.20 18.48 diseases of the heart n 20,395 7,870 <0.001 % 14.84 17.69 other lower respiratory disease n 20,785 8,840 <0.001 % 15.12 19.87 other upper respiratory disease n 19,394 8,029 <0.001 % 14.11 18.05 other nervous system disorders n 14,801 6,211 <0.001 % 10.77 13.96 other gastrointestinal disorders n 13,438 6,310 <0.001 % 9.78 14.18 treatment patterns • a small majority of patients (51.6%) had received treatment with prescription antiperspirants. • twelve-month adherence as measured by pdc was low for prescription antiperspirants (mean±sd 13±9%) (table 2). • only 13.1% were treated with oral systemic therapies; mean±sd time to treatment was 16.9±19.1 months and mean±sd pdc was 30±28%. • post-index medical procedures and surgical options were uncommon (figure 3). figure 3. treatments in the hyperhidrosis cohort es/ps antiperspirants n=22,954 oral systemic therapies n=5,823 botulinum toxin a n=1,104 microwave thermolysis n=58 suction curettage n=70 iontophresis n=463 endoscopicthoracic sympathectomy n=85 51.6 13.09 2.48 0.13 0.16 1.04 0.19 60 10 20 30 40 50 0 p er ce nt ag e of p at ie nt s r ec ei vi ng t he ra py abbreviations: es: extra strength; ps: prescription strength table 2. utilization of pharmacy treatment for hyperhidrosis prescription-strength antiperspirants oral systemic therapies percentage of patients receiving treatment 51.6% 13.1% time to first treatment (mean±sd months) 1.4±6.3 16.9±19.1 twelve-month pdc (mean±sd) 13±9% 30±28% emotional health characteristics • compared with the cc, a higher percentage of patients with hyperhidrosis had any depression/anxiety reported during the uniform twelve-month post-index period (41.1% vs. 28.2%), p<0.001). this corresponded to a higher odds of depression/anxiety in patients with hyperhidrosis (odds ratio=1.76, 95% confidence interval 1.72-1.80, p<0.001) while controlling for other factors. • patients with hyperhidrosis also had a higher percentage of newly diagnosed depression/anxiety during the 12-month post-index period with no evidence of depression/anxiety prior to the index date (18.2% vs. 10.6%, p<0.001). • during the full pre-index and post-index periods, 55.6% of patients with hyperhidrosis had any depression/anxiety reported, including 36.9% with newly diagnosed depression/anxiety. figure 4. patients with depression and/or anxiety during pre-index and 12-month follow-up period pre-index depression 18.4 13.0 12-month f/u period depression 21.6 14.3 pre-index anxiety 22.4 15.9 12-month f/u period anxiety 27.8 17.4 pre-index depression or anxiety 35.2 26.0 12-month f/u period depression or anxiety 41.1 28.2 45 10 20 30 35 25 15 5 40 0 p er ce nt ag e of p at ie nt s hyperhidrosis control total observation period includes pre-index and 12-month follow-up period. limitations • all claims databases have certain inherent limitations affecting generalizability. presence of a diagnosis code on a medical encounter or outside claim may have not been conclusive or positive presence of disease, as the diagnosis code may have been incorrectly coded or included as rule-out criteria rather than actual disease. however, this risk was mitigated by the requirement that patients had at least two claims for the condition of interest. • procedure codes for botulinum toxin a, microwave thermolysis, suction curettage, iontophoresis, and endoscopic thoracic sympathectomy, and pharmacy codes for oral systemic therapies, were generally not specific to the treatment of hyperhidrosis. the study attempted to mitigate this limitation by requiring that patients not have any non-specific codes for these procedures or pharmacy codes for oral systemic therapies within seven days before or after the index date. however, in the follow-up period all instances of these procedures and medications were counted since it was not possible to distinguish usage for the treatment of hyperhidrosis. • results and conclusions are limited to the patient population, which consists of patients enrolled in managed care plans, and may not be generalizable to other commercially insured populations in the us. conclusions • in this real-world database analysis, hyperhidrosis was associated with an increased likelihood of depression and/or anxiety. • despite the comorbidity profile and quality-of-life impact, relatively low percentages of patients received topical or oral systemic prescription or surgical treatments, suggesting that tolerability, efficacy, and awareness may be limiting factors as well as patients not being treated in a timely manner. references 1. smith cc, pariser d. primary focal hyperhidrosis. up-to-date 2018: https://www.uptodate.com/contents/primary-focal-hyperhidrosis?search=hyperhidrosis&source=se arch_result&selectedtitle=1~150&usage_type=default&display_rank=1. 2. doolittle j, walker p, mills t, thurston j. hyperhidrosis: an update on prevalence and severity in the united states. arch dermatol res 2016; 308(10):743-749. 3. clinical classification software (ccs) for icd-9-cm/icd-10-cm. agency for healthcare research and quality, rockville, md. www.hcup-us.ahrq.gov/toolssoftware/ccs/ccs.jsp; www.hcup-us.ahrq.gov/toolssoftware/ccs10/ccs10.jsp 4. bahar r, zhou p, liu y, huang y, phillips a, lee tk, su m, yang s, kalia s, zhang x, zhou y. the prevalence of anxiety and depression in patients with or without hyperhidrosis (hh). j am acad dermatol. 2016 dec;75(6):1126-1133. acknowledgements these studies were funded by dermira, inc. graphics support was provided by prescott medical communications group (chicago, il), with financial support from dermira, inc. disclosures mh, jpb: employees of optum life sciences. kkg: employee of dermira, inc. szk: consultant for dermira, inc. dupilumab in moderate-to-severe atopic dermatitis: pooled efficacy results from two identically designed randomized phase 3 trials (solo 1 & 2) presented at the 2017 fall clinical dermatology conference; las vegas, nv, usa; october 12-15, 2017. carlos ferrándiz1, pablo de la cueva dobao2, eric l. simpson3, rick zhang4, abhijit gadkari5, laurent eckert6, bolanle akinlade5, marius ardeleanu5 1hospital universitario germans trias i pujol, barcelona, spain; 2hospital universitario infanta leonor, madrid, spain; 3oregon health & science university, portland, or, usa; 4regeneron pharmaceuticals, inc., basking ridge, nj, usa; 5regeneron pharmaceuticals, inc., tarrytown, ny, usa; 6sanofi, chilly-mazarin, france b a c k g r o u n d o b j e c t i v e s c o n c l u s i o n s 4–7 m e t h o d s study design treatments outcomes r e s u lt s baseline demographics and disease characteristics patient-reported symptoms and quality of life p safety references acknowledgments disclosures ferrándiz c: de la cueva dobao p: simpson el: zhu x, gadkari a, akinlade b, ardeleanu m: eckert l: dupilumab 300 mg sc qw placebo sc qw maintenance study open-label extension post-treatment options: safety follow-up through week 28 screening dupilumab 300 mg sc q2w treatment period (16 weeks) follow-up period (12 weeks) loading dose on day 1a day –35 to –1 baseline week 28week 16 r figure 1. solo 1 and solo 2: pivotal phase 3 studies with identical study design. table 1. baseline disease characteristics. 0 10 20 30 40 50 60 70 80 90 100 p a ti e n ts ( % ) 9.3 37.0 36.8 * * *p < 0.0001 vs placebo iga = 0 or 1 and ≥ 2-point reduction from baseline at week 16 a b easi-75 at week 16 *p < 0.0001 vs placebo 0 10 20 30 40 50 60 70 80 90 100 13.3 47.7 50.2 * * placebo dupilumab 300 mg q2w dupilumab 300 mg qw figure 2. iga 0/1 and ≥ 2-point improvement from baseline (a) and easi-75 (b) at week 16. –60 –100 –70 –40 –50 –30 –20 –10 0 0 1 2 4 6 8 12 16 l s m e a n % c h a n g e in e a s i sc o re fr o m b a se lin e ( ± s e ) –10 l s m e a n % c h a n g e in s c o r a d to ta l s c o re f ro m b a se lin e ( ± s e ) easi study week –34.3 –70.0* –70.7* –80 –90 *p < 0.0001 vs placebo –60 –100 –70 –40 –50 –30 –20 0 0 1 2 4 6 8 12 16 scorad study week –24.0 –54.3* –55.2* –80 –90 *p < 0.0001 vs placebo a b placebo dupilumab 300 mg q2w dupilumab 300 mg qw figure 3. percent change from baseline in easi score (a) and scorad score (b). placebo dupilumab 300 mg q2w dupilumab 300 mg qw –2 l s m e a n c h a n g e in p o e m sc o re f ro m b a se lin e ( ± s e ) –12 –8 –10 –6 –4 0 0 1 2 4 6 8 12 16 poem study week pruritus nrs improvement ≥ 4-points from baseline –4.2 –10.9* –11.2* *p < 0.0001 vs placebo a b p a ti e n ts ( % ) study week 10.9 38.4* * * 39.6* *p < 0.0001 vs placebo 0 0 10 20 30 40 50 60 70 80 90 100 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 figure 4. proportions of patients achieving peak pruritus nrs score improvement of ≥ 4 points at week 16 (a), and change from baseline in poem score (b). –1 0 0 1 2 4 6 8 12 16 l s m e a n c h a n g e in h a d s t o ta l sc o re f ro m b a se lin e ( ± s e ) –1 l s m e a n c h a n g e in d l q i sc o re f ro m b a se lin e ( ± s e ) hads total score study week –1.6 –5.1* –5.5* –2 –3 –4 –5 –6 *p < 0.0001 vs placebo –6 –10 –7 –4 –5 –3 –2 0 0 1 2 4 6 8 12 16 dlqi study week –4.3 –9.2* –9.3* –8 –9 *p < 0.0001 vs placebo a b placebo dupilumab 300 mg q2w dupilumab 300 mg qw figure 5. change from baseline in hads total score (a) and dlqi score (b). table 2. adverse events. c c patient eligibility clinical efficacy p p p p pruritus p p fc17posterregeneronsanofiferrandizdupilumabatopicdermatitis.pdf continuous weekly adalimumab is the optimal long-term strategy for patients with moderate-to-severe hidradenitis suppurativa: results from the pioneer open label extension trial alexa b kimball,1 martin m okun,2 gerit mulder3 1harvard medical faculty physicians at beth israel deaconess medical center, boston, ma, usa; 2fort healthcare, fort atkinson, wi, usa; 3abbvie inc, north chicago, il, usa introduction 1. kimball a, et al. n engl j med. 2016;375:5. • determine the effectiveness of retreatment with adaew in patients with moderate-to-severe hs, following dose withdrawal or reduction. • the optimal long-term strategy for managing hs patients with adalimumab appeared to be continuous weekly dosing, as either a short-term reduction of dose to every-other-week or treatment withdrawal (placebo) was associated with modest loss of long-term response. • this conclusion is limited by the small number of evaluable patients in this analysis. • no new safety risks were identified. • adalimumab (originator) 40 mg weekly dosing (adaew) is approved for treatment of moderate-to-severe hidradenitis suppurativa (hs). • there are clinical circumstances where patients are obliged to temporarily discontinue or reduce this dose. • this is a pooled analysis of 3 trials that evaluated 40 mg adaew in patients with moderate-to-severe hs: – the phase-3 placebo-controlled pioneer i & ii trials evaluated the efficacy and safety of adaew vs placebo.1 – the subsequent open-label extension trial (ole) (nct01635764) determined the long-term safety and efficacy of adaew. • in pioneer i & ii, patients randomized to 40 mg adaew in the 12-week period a were re-randomized at week 12 to 40 mg adaew, 40 mg ada every-otherweek (eow), or placebo for 24 weeks (period b) (figure 1). • at week 36 of the trial (week 24 of period b), patients had the option to enter the ole and receive 40 mg adaew. patients who discontinued during period b due to loss of treatment response or lack/worsening of disease improvement could also enter the ole at discontinuation. figure 1. study schematic of pioneer i and ii, and the ole randomization 1:1 screening period a double-blind placebo-controlled 12 weeks period b 0 12 16 36week: ada 40 mg weekly placebo ada 40 mg every-other-week placebo pioneer i: ada 40 mg weekly pioneer ii: placebo open-label extension (ole) at least 60 weeks ada 40 mg weekly, open-label ada 40 mg weekly double-blind placebo-controlled 24 weeks randomization: stratified by baseline hurley stage ii vs iii (pioneer i & ii) & baseline concomitant antibiotic use (pioneer ii). re-randomization for period a ada patients: stratified by week 12 hiscr status at entry into period b, & by baseline hurley stage ii vs iii. period a: patients started ada at week 4 after 160 mg (week 0), 80 mg (week 2). patients receiving placebo in period a, and ada or placebo in period b, were not included in this analysis. abbreviations: ada=adalimumab; hiscr=hidradenitis suppurativa clinical response. table 1. pioneer i and ii key eligibility/exclusion criteria inclusion exclusion • adults, anti-tnfα-naïve, diagnosed with hs for ≥1 year prior to baseline • no prior treatment with anti-tnf agents • inadequate response to oral antibiotics for the treatment of hs • no other active skin disease that could interfere with assessment of hs • total abscess and inflammatory nodule (an) count of ≥3 • draining fistula count of >20 at baseline • hs lesions in ≥2 body areas, one of which was hurley stage ii or iii • the primary outcome measure was hiscr (hidradenitis suppurativa clinical response) defined as a ≥50% reduction in total abscess and inflammatory nodule (an) count with no increase in abscess and draining fistula counts. • pioneer i & ii results were pooled. retreatment was evaluated for patients receiving adaew in the ole following withdrawal (placebo) or dose reduction (adaeow) in period b. • the patients in this analysis from pioneer i & ii were intent-to-treat. • treatment groups are listed by treatment received in period a/period b/ole. table 3. patient status, pioneer ole patient status adaew/ew/ew n=88 adaew/eow/ew n=90 adaew/pbo/ew n=92 n % n % n % dosed 88 100 90 100 92 100 completed study 37 42.0 44 48.9 44 47.8 discontinued study 51 58.0 46 51.1 48 52.2 primary reason: ae 7 8.0 11 12.2 5 5.4 lack of efficacy 15 17.0 10 11.1 17 18.5 withdrew consent 15 17.0 9 10.0 16 17.4 lost to follow up 7 8.0 11 12.2 8 8.7 exceeded protocol specified number of interventions 0 0 0 0 1 1.1 protocol deviations 1 1.1 0 0 0 0 other 6 6.8 5 5.6 1 1.1 abbreviations: ae=adverse event table 2. baseline patient characteristics, pioneer ole adaew/ew/ew n=88 adaew/eow/ew n=90 adaew/pbo/ew n=92 n % n % n % sex female 56 63.6 60 66.7 50 54.3 male 32 36.4 30 33.3 42 45.7 race white 81 92.0 70 77.8 75 81.5 black 4 4.5 16 17.8 12 13.0 other 3 3.4 4 4.4 5 5.4 bmi,a kg/m2 <25 (normal weight) 14 15.9 19 21.1 20 22.0 25 to <30 (overweight) 23 26.1 23 25.6 17 18.7 30 to <40 (obese) 40 45.5 35 38.9 42 46.2 ≥40 (morbidly obese) 11 12.5 13 14.4 12 13.2 nicotine user 52 59.1 55 61.1 48 52.2 hurley stage ii 42 47.7 47 52.2 51 55.4 iii 46 52.3 43 47.8 41 44.6 median range median range median range age, year 35.5 18-64 36.0 19-63 35.0 20-67 lesion count an 9.0 3-71 9.0 3-78 10.0 3-50 draining fistulas 2.0 0-19 2.0 0-20 2.5 0-20 abscess 1.0 0-13 2.0 0-14 1.0 0-17 inflammatory nodules 7.0 0-69 7.0 2-76 8.0 0-38 modified sartorius score 103.0 158-1093 100.0 139-433 107.0 162-397 prior hs duration, years 10.3 1.0-40.4 8.5 1.1-32.9 8.2 1.1-43.5 pain at worst, nrs 4.6 0-9.7 4.7 0-10.0 4.4 0-8.4 dlqi, range 0-30 16.0 2-30 14.5 1-30 14.0 0-30 hscrp, mg/l 6.5 0.2-189.0 7.8 0.3-104.0 9.1 0.2-95.2 a. data missing: bmi, adaew/pbo/ew, n=1. abbreviations: ada=adalimumab; ew=every-week dosing; eow=every-other-week dosing; pbo=placebo; bmi, body mass index; an=total abscess and inflammatory nodule count; hs=hidradenitis suppurativa; nrs=numerical rating scale; dlqi=dermatology life quality index score; hscrp=high-sensitivity c-reactive protein. figure 2. patients achieving hiscr, n (%), by ole dose groups abbreviations: ada=adalimumab; ew=every-week dosing; eow=every-other-week dosing; pbo=placebo. 34.1 52.3 62.5 62.5 56.8 60.2 56.8 39.8 55.6 54.4 57.8 56.7 56.7 52.2 34.1 51.1 52.2 58.7 55.4 53.3 45.7 0 20 40 60 80 100 2 12 36 60 84 108 120 p a tie n t s , % ada ew/ew/ew, n=88 ada ew/eow/ew, n=90 ada ew/pbo/ew, n=92 week: 30 (n=88) 46 55 55 50 53 50 35 (n=88) 50 49 52 51 51 47 31 (n=91) 47 48 54 51 49 42 n= |period a|-------period b-------|------------------------------------------period c------------------------------------------| 34.1 53.5 63.2 66.7 66.7 75.0 69.6 39.8 56.2 54.1 61.6 59.0 60.0 53.7 65.9 51.6 53.5 71.6 67.7 66.1 53.8 0 20 40 60 80 100 2 12 36 60 84 108 120 p a tie n t s , % ada ew/ew/ew ada ew/eow/ew ada ew/pbo/ew week: 31/91 47/91 46/86 48/67 42/62 37/56 28/52 35/88 50/89 46/85 45/73 36/61 33/55 29/54 31/91 47/91 46/86 48/67 42/62 37/56 38/52 n/n= |period a|-------period b-------|------------------------------------------period c------------------------------------------| last observation carried forward as observed safety • the rate of any treatment-emergent adverse event (ae) was similar among the treatment groups (figure 3). the rate of serious infections was low, and similar among the treatment groups. figure 3. rate of treatment-emergent adverse events abbreviations: ada=adalimumab; ew=every-week dosing; eow=every-other-week dosing; pbo=placebo; ae=adverse event; tb=tuberculosis; d/c=discontinued. 86.4 13.6 14.8 71.6 3.4 23.0 77.8 16.7 12.2 57.8 1.1 2.2 81.5 20.7 8.7 51.1 2.2 3.3 0 20 40 60 80 100 p a tie n t s , % ada ew/ew/ew, n=88 ada ew/eow/ew, n=90 ada ew/pbo/ew, n=92 any ae serious ae leading to study drug d/c infection serious infection tb (active or latent) n= 76 70 75 12 15 19 13 11 8 63 52 47 3 1 2 2 2 3 • lymphoma was reported by one patient (adaew/pbo/ew), non-melanoma skin cancer (nmsc) was reported by one patient (adaew/pbo/ew), and malignancy other than lymphoma or nmsc, by 2 patients (one adaew/eow/ew and one adaew/pbo/ew). • serious ae infections for adaew/ew/ew were reported by 3.4% of patients (cellulitis, n=1; pneumonia, n=2); for adaew/eow/ew, 1.1% (vulval abscess, n=1), and for adaew/pbo/ew, 2.2% (cellulitis, n=1; pilonidal cyst, n=1). • there were no deaths in these 3 groups. disclosures akl received honoraria as a consultant and grants as an investigator from janssen, abbvie, amgen, and novartis and has received fellowship funding from janssen. mo received honoraria from abbvie for advisory board participation and speaker services, and from abbvie, gilead science, and crescendo biosciences for consultant services. dr. okun was an abbvie employee during this study. gm received a salary as abbvie employees, and may have also received stocks and/or stock options. abbvie inc. funded this study and participated in the study design; study research; collection, analysis and interpretation of data; and writing, reviewing and approving of this publication. all authors had access to the data, and participated in the development, review, and approval, and in the decision to submit this publication. the authors would like to acknowledge piyalal karunaratne, former abbvie employee, for statistical support, and jody bennett, employed by abbvie, for medical writing support in the production of this publication. objective materials & methods results efficacy • patients sustained response to adaew throughout pioneer and the ole, regardless of whether they experienced dose reduction or dose withdrawal during period b (week 12-36). • more patients who remained on adaew throughout pioneer and the ole, achieved response as measured by hiscr (figure 2). conclusionsreferences presented at the fall clinical dermatology conference 36th anniversary • las vega, nevada • october 12 – 15, 2017 fc17posterabbviekimballcontinuousweeklyadalimumab.pdf powerpoint presentation 31-gene expression profile assessing metastatic risk in melanoma patients: issues impacting patient selection ryan m. svoboda, md ms1, alex m. glazer, md2, darrell s. rigel, md ms3* background objective methods results limitations conclusions 1national society for cutaneous medicine, new york, ny 2division of dermatology, university of arizona, tucson, az 3ronald o. perelman dept. of dermatology, nyu medical center, new york, ny • genetic evaluation of melanoma plays an increasingly important role in clinical practice • a 31-gene expression profiling (31-gep) test (decision-dxmelanoma, castle biosciences, inc., friendswood, tx) to predict metastatic risk in cutaneous malignant melanoma (cmm) has been validated and is available for clinical use • the impact of the results of this test on clinical decision making has been studied, but little is known about which clinical factors impact dermatologists’ decision to utilize the test • to determine which factors impact the decision to utilize the 31gep test for metastatic risk stratification in cmm patients *disclosures: dr. rigel serves as a consultant to and on the advisory board for castle biosciences. drs. svoboda and glazer participated in research fellowships funded in part by castle biosciences. • 181 dermatologists attending the 2017 winter clinical dermatology conference-hawaii® completed a series of questions based around four clinical vignettes using an audience response system • vignettes assessed the impact of three factors on the decision to order the 31-gep test: • breslow thickness • ulceration • sentinel lymph node biopsy (slnbx) status • chi-squared tests were used to compare the proportion of respondents who would order the test at baseline and in the presence of ulceration and a negative slnbx for each breslow thickness patient vignette age, gender melanoma location breslow thickness 1 45, female right leg 0.76 mm 2 42, male right back 0.50 mm 3 35, male right arm 0.26 mm 4 72, female right neck 2.10 mm clinical characteristics of patient vignettes • subjects were given a brief introductory lecture on the background of the 31-gep test immediately prior to the survey; this may have introduced bias • sample may not be representative of the overall population of practicing united states dermatologists • a majority of dermatologists in this sample would order the 31-gep test for melanomas of any breslow thickness in the presence of ulceration and melanomas with breslow thickness ≥ 0.50 mm in the absence of ulceration • despite the fact that 2/3rds of cmm patients who develop metastases initially have a negative slnbx, negative slnbx status does not seem to be a significant stimulus to ordering the test percentage of dermatologists who would order 31-gep test in different clinical scenarios *statistically significant **p-value comparing proportion who would order test at baseline and in presence of ulceration or sln negative status for given thickness breslow thickness 0.26 mm 0.50 mm 0.76 mm 2.1 mm p-value* non-ulcerated 22% 78% 61% 74% <0.001 ulcerated 67% 87% 80% 72% <0.001 percent of sample who would use 31-gep test to predict metastatic risk in malignant melanoma *using chi-squared test to compare the proportion who would order the 31-gep test at each breslow thickness ¾ primary efficacy analysis (mitt population) included 194 subjects: 400 mg qd (48), 800 mg qd (53), 400 mg bid (46), and placebo (47). ¾ least squares mean percent change from baseline was statistically significant compared with placebo for the 800 mg qd group (-48.2% vs -25.0%; p=.001) and the 400 mg bid group (-50.7% vs -25.0%; p<.001); the difference between 400 mg qd and placebo did not reach statistical significance (-38.1% vs -25.0%; p=.066) (table 1) (figure 1). ¾ diarrhea was the most common teae, reported in 22.4%, 40.0%, 39.6%, and 14.6% of subjects in the xp-23829 400 mg qd, 800 mg qd, 400 mg bid, and placebo groups, respectively. most cases of diarrhea were mild to moderate in severity (table 2). ¾ nausea and abdominal pain were reported in more than 10% of the overall xp-23829 population (table 2). ¾ flushing was reported in 5.9% of xp-23829 subjects and 6.3% of placebo subjects (table 2). ¾ no subject demonstrated grade 3 or 4 lymphopenia (table 2). ¾ no new or unexpected adverse events related to xp-23829 were reported compared to what is known for the fae class (table 2). xp-23829, a novel fumaric acid ester, is efficacious in reducing psoriatic lesions: results from a phase 2 randomized controlled study alice b. gottlieb, md, phd1; caitriona ryan, md2; richard kim, md3; aftab alam, mbbs, ms, mba4; sagar munjal, md, ms4; leon kircik, md5 1new york medical college, valhalla, ny; 2st. vincent’s university hospital, dublin, ireland; 3rkk consulting, inc, redwood city, ca; 4promius pharma, a subsidiary of dr. reddy’s laboratories, princeton, nj; 5dermresearch, pllc, louisville, ky conclusions ¾ in this study xp-23829 in 400 mg bid and 800 mg qd doses demonstrated significant efficacy over 12-week of treatment and efficacy did not appear to have plateaued at the end of the study. ¾ efficacy and safety is being further assessed in a 24-week phase 2 study. methods table 1. least squares mean for percentage change in total pasi score ¾ randomized, double-blind, placebo-controlled, dose-finding efficacy and safety study in 33 us sites. ¾ patients with chronic plaque psoriasis > 6 months, pasi (psoriasis area and severity index) ≥ 12, spga (static physician global assessment) ≥ 3, and psoriasis bsa (body surface area) ≥ 10%. ¾ 200 subjects randomized in a 1:1:1:1 ratio into 4 arms: 400 mg qd, 400 mg bid, 800 mg qd, placebo. ¾ a 3-week titration phase was followed by 9 weeks of treatment. ¾ the primary endpoint was the percentage change in pasi score from baseline to the end of week 12. financial support: this study was supported by the dr reddy’s laboratories group of companies and by xenoport, inc. now arbor pharmaceuticals, llc. drl publication #816 results introduction ¾ dimethyl fumarate (dmf) is a fumaric acid ester (fae) approved in germany for the treatment of moderate to severe chronic plaque psoriasis. monomethyl fumarate (mmf) is the active moiety of dmf. ¾ xp-23839 is an extended release fae that is being developed for the treatment of moderate to severe plaque psoriasis. ¾ here, we examine a phase 2 study to evaluate the safety and efficacy of 3 doses and 2 dosing regimens at 12 weeks. table 2. frequent treatment-emergent adverse effects (≥10%) xp-23829 400 mg qd (n=48) xp-23829 800 mg qd (n=53) xp-23829 400 mg bid (n=46) placebo (n=47) overall mitt population lsm (se) p value vs placebo lsm (se) p value vs placebo lsm (se) p value vs placebo lsm (se) week 12 -38.1 (5.07) 0.066 -48.2 (5.06) .001 -50.7 (5.50) < .001 -25.0 (5.06) xp-23829 400 mg qd (n=49) xp-23829 800 mg qd (n=55) xp-23829 400 mg bid (n=48) xp-23829 (n=152) placebo (n=48) any teae 36 (73.5) 42 (76.4) 37 (77.1) 115 (75.7) 29 (60.4) diarrhea 11 (22.4) 22 (40.0) 19 (39.6) 52 (34.2) 7 (14.6) nausea 6 (12.2) 4 (7.3) 10 (20.8) 20 (13.2) 6 (12.5) abdominal pain 1 (2.0) 7 (12.5) 11 (22.9) 19 (12.5) 2 (4.2) flushing 4 (8.2) 3 (5.5) 2 (4.2) 9 (5.9) 3 (6.3) headache 2 (4.1) 3 (5.5) 5 (10.4) 10 (6.6) 2 (4.2) vomiting 3 (6.1) 7 (12.7) 1 (2.1) 11 (7.2) 1 (2.1) lsm = least squares mean; se = standard error figure 1. least squares mean % change from baseline in pasi score over time ppn-06 vs fumaderm table 3. maximum lymphocyte grades at any given visit 400 mg qd (n=49) 800 mg qd (n=55) 400 mg bid (n=48) placebo (n=48) grade 1 3 (6.1%) 5 (9.1%) 7 (14.6%) 2 (4.2%) grade 2 2 (4.1%) 2 (3.6%) 1 (2.1%) 0 grade 3 or 4 0 0 0 0 -60 -50 -40 -30 -20 -10 0 0 1 2 3 4 5 6 7 8 9 10 11 12 p er ce nt c ha ng e week ppn-06 phase 2 placebo ppn-06 400 mg qd ppn-06 800 mg qd ppn-06 400 mg bid -25.0 -38.1 -48.2 -50.7 titration steady-state dosing fc17posterpromiusgottliebxp23829.pdf powerpoint presentation visual assessment and dermoscopy enhanced by non-invasive genomic testing 1. dermatologic surgery center of dc, chevy chase, md, 2. dermtech, inc. la jolla, ca. 3. department of dermatology, georgetown, university school of medicine, washington, dc methods non-invasive genomic analysis was conducted using adhesive patches (dermtech, inc., la jolla, ca) to collect tissue from the stratum corneum of all 59 melanomas. nucleic acids extracted from the tissue samples were assessed for prame and linc rna, and in cases with sufficient material, dna was sequenced to detect mutations in the tert promoter region. gene expressions of prame and linc were quantified by qpcr, and tert dna mutations were assessed by sanger sequencing.13,15 histopathologic diagnoses were established by routine light microscopy (supplemented in many cases by immunohistochemistry) and confirmed by consensus discussions with dermatopathologists at two university tumor boards. 1. petrie t, samatham r, witkowski am, esteva a, leachman sa. melanoma early detection: big data, bigger picture. j invest dermatol. 2019;139(1):25-30. 2. dinnes j, deeks jj, chuchu n, et al. dermoscopy, with and without visual inspection, for diagnosing melanoma in adults. cochrane database sys rev. 2018;12(12):cd011902. 3. wolner zj, yelamos o, liopyris k, rogers t, marchetti ma, marghoob aa. enhancing skin cancer diagnosis with dermoscopy. dermatol clin. 2017;35(4);417-437. 4. argenziano g, kittler h, ferrara g, et al. slow-growing melanoma: a dermoscopy follow-up study. br j dermatol. 2010;162(2):267-273. 5. lallas a, longo c, manfredini m, et al. accuracy of dermoscopic criteria for the diagnosis of melanoma in situ. jama dermatol. 2018;154(4):414-419. 6. rose se, argenziano g, marghoob aa. melanomas difficult to diagnose via dermoscopy. g ital dermatol venereol. 2010;145(1):111-126. 7. gerami p, yao z, polsky d, et al. development and validation of noninvasive 2-gene molecule assay for cutaneous melanoma. j am acad dermatol. 2017;76(1):114120.e112. 8. skelsey mk, rock j, howell md, et al. non-invasive detection of genomic atypia increases real-world npv and ppv of the melanoma diagnostic pathway and reduces biopsy burden. skin. 2021;5(5):512-523. 9. jackson sr, jansen, b, yao z, et al. risk stratification of severely dysplastic nevi by non-invasively obtained gene expression and mutation analysis. skin. 2020;4(2):105110. 10. markowitz o. a practical guide to dermoscopy. wolters kluwer; 2017:9-23. 11. ferris lk, jansen b, ho j, et al. utility of a noninvasive 2-gene molecular assay for cutaneous melanoma and effect of the decision to biopsy. jama dermatol. 2017;153(7):672-680. 12. ianosi sl, calbureanu-popescu mx, ianosi ng, et al. the importance of dermoscopy in early recognition of melanoma in situ. curr health sci j. 2019;45(4):366-371. 13. petty aj, ackerson b, garza r, et al. meta-analysis of number needed to treat diagnosis of melanoma by clinical setting. j am acad dermatol. 2020;82(5):1158-1165. references results of 59 melanomas, 42 (71.1%) were in situ and 17 (28.8%) were invasive melanoma. all melanomas were positive for 1 or more melanomaassociated genomic markers. in situ lesions had an average of 3.48 (range 0-7) dermoscopic features while invasive melanomas had an average of 4.71 (range 2-7) (p=0.05). half of the 42 in situ melanomas (n=21, 50%) and 3 of 17 (18%) invasive melanomas had 3 or fewer dermoscopic features (figure 1). when combining dermoscopic and clinical features, the average number of features for in situ lesions was 6.29 (range 1-9) compared to invasive lesions with 8.18 features (range 4-11, p=0.02). by non-invasive genomic assessment, 29 lesions (49.2%) expressed 2 genomic markers, 28 (47.5%) expressed prame and linc and 1 lesion (1.7%) expressed prame and tert. twenty-eight lesions (47.5%) expressed 1 marker, 19 (32.2%) expressed linc only, 7 (11.9%) expressed prame only, and 2 (3.4%) expressed tert only. two lesions (3.4%) expressed all 3 markers (linc, prame, and tert). the most common genomic marker detected was linc (n=50, 84.7%) followed by prame (n=39, 66.0%). figure 1 depicts examples of assessed cases of in situ melanomas with few or subtle dermoscopic features and the genomic markers present in the lesions. conclusion evaluating pigmented lesions to rule out melanoma and appropriately guide biopsy decisions remains challenging, even for experienced dermoscopists.12,13 earlier in situ and some invasive melanomas can have few or minimal morphologic features on visual and dermoscopic inspection.5,6 non-invasive genomic testing may enhance biopsy decision making in this situation.7-9,11 a. in situ, minimal dermoscopic features (linc and prame) b. in situ, minimal dermoscopic features (prame) figure 1. examples of in situ melanomas with minimal features (genomic markers present) figure 1. number of dermoscopic features for in situ and invasive melanomas. gary l. peck, md1, rachel a. reifer, bs1, mark a. hyde, phd2, sarah w. matthews, dnp2, burkhard jansen, md2, maral k. skelsey, md1,3 clinical features asymmetry, border irregularity, color variability (black pigment was assessed separately), and diameter >6 mm. dermoscopic features absent or diminished pigment network, regression structures, granularity (peppering), globular disorganized pigment network, reticular disorganized pigment network, homogeneous disorganized pigment network, radial streaming, network thickening at the periphery, focal pseudopods, vascular changes (twisted, dotted), negative pigment network, shiny white lines, and blue-grey-white veil. methods (cont.) results (cont.) a b . . funding/disclaimer: study site was reimbursed by dermtech for the collection of data; three authors are employed by dermtech. introduction and objective early detection of melanoma is critical to optimizing patient outcomes.1 dermoscopy supports visual inspection of pigmented lesions that raise concern for melanoma,2 and generally improves overall accuracy when ruling out melanoma.3 numerous dermoscopic findings have been proposed as sensitive and specific features of melanoma, and various combinations of them have been used to generate checklists and algorithms to aid in biopsy decision-making.2 however, since melanoma-specific dermoscopic criteria are complex and have primarily been studied within invasive melanomas, they may be less reliable for in situ melanoma.4-6 in addition, the performance of dermoscopy is influenced by the training and experience of the user.2 for these reasons, alternative approaches to pigmented lesion assessment continue to be of interest. non-invasive assessment of melanoma-associated genomic biomarkers has been shown to be effective in ruling out melanoma in uncertain pigmented skin lesions with a sensitivity of 91-97%, specificity of 53-69%, and negative predictive value >99%.7,8 rna gene expression of preferentially expressed antigen in melanoma (prame) and long intergenic non-coding rna 518 (linc), along with somatic dna mutations in telomerase reverse transcriptase (tert), are detected in samples of stratum corneum overlying pigmented lesions collected non-invasively using adhesive patches.7 the objective of this retrospective case series analysis was to determine whether non-invasive assessment of genomic biomarkers could enhance visual and dermoscopic detection of pigmented lesions at risk for melanoma. the emr of a large dermatology practice was queried for all melanomas diagnosed during a one-year period, which revealed 59 cutaneous melanomas, all 59 had undergone non-invasive genomic assessment,7,9 and a checklistguided dermoscopic exam performed by a dermatologist highly experienced in dermoscopy prior to biopsy (g.p., confirmed by m.k.s.). clinical and dermoscopic images were available for all lesions, each of which was reviewed for 5 clinical and 13 dermoscopic features (table 1).10 table 1. clinical and dermoscopic features in situ n=42 invasive n=17 dermoscopic features n % n % 0 3 7% 0 0% 1 0 0% 0 0% 2 4 10% 1 6% 3 14 33% 2 12% 4 13 31% 5 29% 5 5 12% 4 24% 6 2 5% 3 18% 7 1 2% 2 12% presented at the winter clinical dermatology conference january 13-18, 2023 slide number 1 skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 850 skinmages disseminated varicella-zoster virus infection in an immunocompetent host alannah mulholland, md, bsc1, brandon tang, md, mscli2, steven shumak, md, frcpc2, linda zhou, md3 1 department of community and family medicine, university of toronto, toronto, on 2 department of medicine, university of toronto, toronto, on 3 department of dermatology and skin science, university of british columbia, vancouver, bc an 84-year-old female with severe parkinson’s disease requiring deep brain stimulator (dbs) presented to the emergency department with a one-week history of unilateral vesicular rash over her left chest. this developed 10 days after replacement of her dbs battery packs located subcutaneously on her chest bilaterally. the erythematous and crusted rash involved cutaneous dermatomes c2-c5 of the left chest, shoulder and back, with areas of purulence over the lateral neck (figure 1). the rash did not cross the midline but involved the pinna and mandible (figure 2). there was no ocular or mucosal involvement, nor facial palsies. the patient was treated empirically with intravenous (iv) acyclovir for presumed disseminated varicella-zoster virus (vzv) infection. she was also given a sevenday course of cefalexin to prevent bacterial superinfection. tissue culture of the lesions confirmed vzv infection. the patient was discharged home with a four-week course of oral acyclovir. herpes zoster is caused by reactivation of vzv which remains dormant in the dorsal root ganglia. disseminated vzv infection is defined by the presence of more than 20 vesicular lesions in three consecutive dermatomes and occurs in 2% of the general population. differential diagnosis of vesicular cutaneous lesions in immunocompetent hosts should include bacterial infection, skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 851 eczema herpeticum, contact dermatitis, bullous drug eruptions, and pemphigus foliaceous. herpes zoster is a clinical diagnosis, however disseminated infection is confirmed by vzv polymerase chain reaction testing. disseminated infection should prompt further investigation for underlying immunodeficiency such as human immunodeficiency virus (hiv) infection, autoimmune disease, malignancy, and immunosuppressant medications.2 the likely cause of reactivation in our patient was the physical stress associated with her dbs battery change. hiv serology returned negative, and she exhibited no evidence of immunodeficiency. early diagnosis and initiation of antiviral treatment reduces morbidity, pain and complications including post-herpetic neuralgia. management should also include analgesics for comfort and institution of airborne precautions.3 conflict of interest disclosures: none funding: none corresponding author: alannah mulholland, md, bsc department of community and family medicine university of toronto, toronto, on email: alannah.mulholland@mail.utoronto.ca references: 1. drone e, ganti l. a case of disseminated zoster in an immunocompetent patient. cureus. 2019 dec 4;11(12). 2. levin, m. and albrecht, m., 2022. epidemiology, clinical manifestations, and diagnosis of herpes zoster. [online] uptodate.com. available at: <https://www.uptodate.com/contents/epidemiolog y-clinical-manifestations-and-diagnosis-ofherpeszoster?search=disseminated%20zoster%20prog nosis&source=search_result&selectedtitle=1~15 0&usage_type=default&display_rank=1> [accessed 8 october 2022]. 3. nair pa, patel bc. herpes zoster. [updated 2022 may 24]. in: statpearls [internet]. treasure island (fl): statpearls publishing; 2022 jan-. available from: https://www.ncbi.nlm.nih.gov/books/nbk441824/ reduc�on of facial redness with resveratrol added to topical product containing green tea polyphenols and caffeine sarah y. siu, georgina m. ferzli and neil brody the department of dermatology, suny downstate medical center, brooklyn, ny, 11203university hospital of brooklyn introduc�on facial redness can occur in associa�on with a large number of medical problems. the most common causes of facial redness and rashes include inflammatory dermatoses, infec�ons, and connec�ve �ssue disorders. rosacea is associated with flushing, erythema, telangiectasia, papules, and pustules. its e�ology is unknown. perioral ocular derma��s is an erythematous erup�on of unknown e�ology while atopic derma��s, an inflammatory skin disease, frequently affects the cheeks in infants and other facial areas in adults. contact derma��s, seborrheic derma��s, psoriasis, celluli�s, discoid lupus erythematosus, dermatomyosi�s, and impe�go are also associated with facial redness *tavadia 2003). chronic sun damage, gene�c flusher-blusher, and acne are also frequently encountered. while redness is the final clinical manifesta�on, the pathophysiology leading to the redness may be quite varied. we refer to the common denominator in all of these as inflamma�on, and we now understand many molecules are involved in the inflammatory process. many of the pathways of inflamma�on involve reac�ve oxygen species (ros). it is probably true quenching ros, should be considered an an�-inflammatory agent. many topical formula�ons include an�oxidants to improve the an�oxidant capability of the skin (berson 2008, farris 2007, palmer 2010). an an�oxidant that has received considerable a�en�on is resveratrol (3,5,4’-trihydroxys�lbene), a polyphenolic phytoalexin found in red wines, colored berries, and peanuts (baxter 2007).the myriad of clinical benefits of resveratrol led to the hypothesis that the addi�on of this agent to a topical prepara�on containing green tea polyphenols and caffeine (both of which protect skin from uv injury [elmets 2001, heffernan 2009]) might be an even more effec�ve skin care product. the present study evaluated the ability of a resveratrol-enriched product containing green tea polyphenols and caffeine to reduce facial redness in human skin. methods stage 1. in a preliminary split-face study, 16 volunteers applied topical an�oxidant product containing green tea polyphenols and caffeine to one side of the face and the same product with resveratrol added to the other side of the face. product was applied twice daily for 12 weeks. both products were well tolerated. a�er 12 weeks subjects with facial redness showed a reduc�on in redness on the side treated with resveratrol-enriched product (data not shown). these results led to the present study in which subjects presen�ng with facial redness applied resveratrol-enriched product to the en�re face to evaluate the consistency of the apparent reduc�on in redness. stage 2. subjects (n = 16) presen�ng with facial redness applied the resveratrol-enriched product twice daily to the en�re face. reduc�on in redness was evaluated and photographed at 2-week intervals for up to 9 weeks. photography was obtained by canfield visia so�ware version 5.2.0 2010-0503a. this unit has a mode that spectrally separates the red por�on of the image allowing enhanced ability to see changes in skin redness. improvement was evaluated by nine trained staff members and 21 house staff residents on a scale of 1 to 9. the baseline score was assigned a value of 5 for each subject. pos�reatment scores lower than 5 denoted redness reduc�on while scores above 5 indicated an increase in redness. evaluators compared photographs taken before treatment and at 2-week intervals for up to 9 weeks. all subjects provided signed informed consent to treatment and photography. results all subjects completed the study. adverse effects were not observed in any subject. data were analyzed by non-parametric sta�s�cs because the 9-point scale is not con�nuous and scoring data were not normally distributed as shown by the shapiro-wilk test. as shown in figure 1, the collec�ve data show that median redness scores ranged from 2 to 6 and that most subjects (69%-99%) achieved a redness reduc�on of at least 1 score level at the end of their treatment period. redness in the remaining subjects (0%-31%) either did not change (0%-19%) or increased by 1 score value (0%-19%). discussion overall, the results suggest that the treatment effect (i.e., reduc�on in facial redness) requires up to 6 weeks of treatment for most subjects. it is possible that subjects achieving redness reduc�on in 3 to 6 weeks may improve further. however, if redness has not been reduced a�er 6 weeks of treatment, it is unlikely that further treatment will reduce redness. clinical examples are presented in figures 2-4. many topical formula�ons include an�oxidants. common examples include the polyphenols (found in tea), vitamin c, vitamin e, silymarin, and soy isoflavones (pinnell 2003). interest in resveratrol became stronger when, in 1997, resveratrol was shown to have cancer chemopreventa�ve effects in tumor ini�a�on, promo�on, and progression stages in humans (jang 1997). resveratrol has since been shown to reduce intracellular hydrogen peroxide-upregulated ros in human fibroblasts in vitro (jagdeo 2010), modulate gene�c expression (baxter 2007), inhibit inflammatory mediators (baxter 2007), prevent skin cancer (aziz 2005), exhibit an�prolifera�ve ac�vity in mul�ple forms of cancer (athar 20078, ding 2002), promote apoptosis in tumor cells (delmas 2003), improve dermal wounds (khanna 2002, sen 2002, khanna 2001), inhibit uvb-induced skin damage (afaq 2003), and protect against ldl oxida�on (brito 2003). resveratrol has also been shown to have an�fungal and an�bacterial proper�es (chan 2002) and to reduce levels of ros in hacat kera�nocytes exposed to uva light (baxter 2007). green tea polyphenols (gtps) are an�oxidants shown in mice to protect against skin inflamma�on and tumorigenesis (mukhtar 1994, ka�yar 2000) and phototoxicity induced by psoralen plus uv-a radia�on (zhao 1999). gtps (catechins) include (—) epicatechin, (—) epicatechin-3-gallate, (—) epigallocatechin, and (—) epigallocatechin-3-gallate deriva�ves. when administered topically in mice, (-)-epigallocatechin-3-gallate protects against photocarcinogenesis (gensler 1996) and is regarded as the most effec�ve catechin. topical caffeine has been shown to protect against uv damage in mice by elimina�ng uv-damaged kera�nocytes (koo 2007) and subsequently inhibi�ng skin cancer development. topical caffeine has also been to inhibit forma�on of galactose cataracts (varma 2010) and improve psoriasis vulgaris (vali 2005). exposure of the skin to uv radia�on induces inflammatory responses associated with a variety of skin disorders, including cancer. regarded as early events in tumor promo�on, development, or both, inflammatory responses are characterized by erythema, edema, hyperplas�c responses, and increases in blood flow blood vessel permeability, and levels of cox-2 and prostaglandin. these responses are also associated with the induc�on of inflammatory cytokines (tumor necrosis factor-α, il-6, and il-1β) (meeran 2009). it is useful to summarize mechanisms by which the combina�on product of the present study reduces facial redness and inflamma�on. facial redness may occur in a variety of inflammatory dermatologic disorders and an effec�ve treatment of facial redness without the side effects of steroids would be useful (oh 2010). since the molecular targets of each component are not iden�cal, the components may act independently and synergis�cally to reduce cutaneous inflamma�on. conclusion the skin product combina�on of resveratrol, green tea polyphenols, and caffeine reduces facial redness in most pa�ents a�er 3 to 6 weeks of con�nuous treatment and may provide further improvement with addi�onal treatment. figure 2. graph of 9 evaluators-natural photo data. a 75-year-old female (skin type 2) before treatment (le�) and 4 weeks a�er treatment with resveratrol-enriched product (right). redness reduc�on was scored at 3. figure 1. median pos�reatment score vs. percentage of subjects for four sets of data. baseline score was set at 5 for each subject. pos�reatment scores less than 5 indicated reduced redness while scores greater than 5 denoted increased redness. figure 3. graph of 9 evaluators-redness photo data. a 72-year-old male (skin type 2) before treatment (le�) and 9 weeks a�er treatment with resveratrol-enriched product (right). redness reduc�on was scored at 3. figure 4. graph of 21 evaluators-natural photo data a 27-year-old female (skin type 1) )before treatment (le�) and 5 weeks a�er treatment with resveratrol-enriched product (right). redness reduc�on was scored at 3. figure 5. graph of 21 evaluatorsredness photo data. the possible role of treatment dura�on on facial redness reduc�on was also evaluated for each of the four data sets (table 1). for the 3 to 6-week treatment period the propor�ons of subjects among the four data sets did not differ significantly by pearson’s chi-square test (p = 0.1967). a similar result (p = 0.1059) was obtained when the 7 to 9 week treatment period data were compared. these results indicate that for each of the four sets of data, the distribu�on of subjects among median scores did not differ significantly within each of the two treatment periods. table 1. distribution of subjects among median scores for the 3 to 6 and 7 to 9week treatment periods for each of the four data sets median score weeks of treatment 3 to 6 7 to 9 9 nat 9 red 21 nat 21 red 9 nat 9 red 21 nat 21 red 2 0 1 4 1 0 0 1 0 3 6 4 3 5 1 0 0 0 4 4 7 2 6 0 3 1 4 5 1 0 2 0 2 1 0 0 6 1 0 1 0 1 0 2 0 х2 = 15.88, df = 12, p = 0.1967 (ns) х2 = 18.33, df = 12, p = 0.1059 (ns) the distributions of subjects among the median scores for the 3 to 6-week treatment period were compared with those for the 7 to 9-week treatment period for each of the four data sets. as shown in table 2, differences in proportions of subjects for the 3 to 6 and 7 to 9-week treatment durations did not achieve statistical significance for any of the four data sets. table 2. comparisons of distributions of subjects among median scores for the 3 to 6 and 7 to 9-week treatment periods median score 9* nat 9* red 21* nat 21* red 3-6† 7-9† 3-6† 7-9† 3-6† 7-9† 3-6† 7-9† 2 0 0 1 0 4 1 1 0 3 6 1 4 0 3 0 5 0 4 4 0 7 3 2 1 6 4 5 1 2 0 1 2 0 0 0 6 1 1 0 0 1 2 0 0 p = 0.1573 (ns) p = 0.1870 (ns) p = 0.3283 (ns) p = 0.2019 (ns) *no. of evaluators. † weeks of treatment. nat = natural photos; red = red images. fc17postertopixsiureductionoffacialredness.pdf acknowledgements: medical writing support was provided by prescott medical communications group (chicago, il) with financial support from ortho dermatologics; ortho dermatologics is a division of bausch health us, llc | presented at winter clinical dermatology conference 2020 • january 17-22, 2020 • kohala coast, hi synopsis ◾ acne is a prevalent disease, occurring in 85% of adolescents1 ◾ prevalence in adults is increasing and it occurs more often in females than males2,3 ◾ in addition, older age and female sex are associated with a greater impact on quality of life (qol)4 ◾ the first lotion formulation of tretinoin 0.05%, developed by utilizing novel polymeric emulsion technology, was efficacious and well tolerated in two phase 3 studies of patients ≥9 years of age with moderate-to-severe acne (nct02932306, nct02965456)5 objective ◾ to assess efficacy and safety of tretinoin 0.05% lotion in females of various age groups with moderate-to-severe acne methods ◾ in two phase 3 double-blind, randomized, multicenter, parallel-group, vehicle-controlled studies, patients ≥9 years of age with moderate-to-severe acne were randomized 1:1 to tretinoin 0.05% lotion or vehicle once daily for 12 weeks • in this study, cerave® hydrating cleanser and cerave® moisturizing lotion (l’oreal, ny) were provided as needed for optimal moisturization/cleaning of the skin ◾ data from these 2 studies were pooled and analyzed post hoc in a subset of female patients by age: 13-19 years, 20-29 years; and 30+ years ◾ efficacy assessments included reductions in inflammatory and noninflammatory lesions, percentage of patients achieving ≥2-grade reduction in evaluator global severity scores (egss), and acne-specific quality of life questionnaire (acne-qol) ◾ cutaneous safety and tolerability were also evaluated results participants ◾ the pooled population included 865 female patients • 13-19 years (tretinoin, n=173; vehicle, n=184) • 20-29 years (tretinoin, n=163; vehicle, n=189) • 30+ years (tretinoin, n=80; vehicle, n=76) ◾ the majority of patients in each age group had an egss score of 3 (moderate) at baseline (13-19 y, 93.3%; 20-29 y, 88.9%; 30+ y, 95.5%) efficacy within age groups (treatment versus vehicle) ◾ at week 12, least-squares mean percent reductions from baseline in inflammatory and noninflammatory lesion counts were significant versus vehicle in the tretinoin-treated 13-19 year group; in the tretinoin-treated older age groups, reductions from baseline versus vehicle were only significant for noninflammatory lesions, which may be due to the limited number of patients in each group (figure 1) tretinoin 0.05% lotion for the once-daily treatment of moderate-to-severe acne vulgaris in females: effect of age on efficacy and tolerability figure 2. percentage of participants achieving ≥2-grade reduction in evaluator global severity scores by age group and visit (itt population, pooled) #( 0% 10% 20% 30% 1.6% week 4 p e rc e n ta g e o f p a rt ic ip a n ts 5.2% 4.3% 2.0% 5.8% 4.6%vehicle: 5.7% week 8 7.6% 12.8% 6.5% 15.2% 10.5% #( 24.4% week 12 17.0% 25.9% 16.8% 30.7% 18.8% 40% 13-19 y (n=173) 20-29 y (n=163) 30+ y (n=80) there were no significant differences across the 3 age groups at weeks 4, 8, or 12. vehicle: 13-19 y (n=184); 20-29 y (n=189); 30+ y (n=76). multiple imputation method used for missing values. itt, intent-to-treat; ls, least squares. figure 3. mean change from baseline at week 12 in quality of life by age group (itt population, pooled) 0 2 4 6 7.5 self-perception m e a n p e rc e n t c h a n g e f ro m b a se lin e 7.0 10.2 8.8 8.8 9.5vehicle: 14 13-19 y (n=173) 20-29 y (n=163) 30+ y (n=80) 8 10 12 im p ro ve m e n t 6.7 role-emotional 6.1 10.0 7.9 7.5 8.6 4.5 role-social 3.8 6.5 6.5 6.4 7.2 5.2 acne symptoms 5.1 9.1 7.4 8.1 7.6 **p≤0.01 vs vehicle. there were no significant differences across the 3 age groups at weeks 4, 8, or 12. vehicle: 13-19 y (n=184); 20-29 y (n=189); 30+ y (n=76). higher scores for each domain reflect improved health-related qol. no imputation for missing values. itt, intent-to-treat; qol, quality of life. safety ◾ in the tretinoin-treated group, mean cutaneous safety and tolerability ratings were all between none (0) or mild (1) within each age group at weeks 4, 8, and 12 ◾ by week 12, any mild, transient increases in cutaneous safety and tolerability in each age group had returned to baseline values or improved (figure 4) ◾ the percentage of patients achieving ≥2-grade egss reduction in each age group was greater with tretinoin treatment versus vehicle, though differences were not significant (figure 2) ◾ qol improvements at week 12 were significant versus vehicle in the tretinoin-treated 20-29 group for self-perception, role-emotional, and acne symptoms (figure 3) across age groups ◾ reductions in inflammatory or noninflammatory lesion counts and the percent of participants with ≥2-grade egss reduction were generally greater in the 20-29 and 30+ age groups compared with the 13-19 age group, although these differences were not statistically significant (figures 1 and 2) ◾ the greatest improvements in qol domains occurred in the 20-29 and 30+ groups compared with the 13-19 group; these differences did not reach statistical significance (figure 3) figure 1. ls mean percent reduction from baseline in inflammatory (a) and noninflammatory (b) lesion counts by age group and visit (itt population, pooled) #( -70% -50% -30% -10% -30.5% week 4 ls m e a n p e rc e n t c h a n g e f ro m b a se lin e a. in�ammatory lesions -27.4% -28.1% -24.1% -34.6% -36.3%vehicle: -44.6% week 8 -37.9% -46.7% -36.4% -50.3% -49.7% #( -55.3% week 12 -45.2% -55.8% -46.6% -63.5% -56.7% 13-19 y (n=173) 20-29 y (n=163) 30+ y (n=80) #( -70% -50% -30% -10% -21.3% week 4 ls m e a n p e rc e n t c h a n g e f ro m b a se lin e b. nonin�ammatory lesions -17.0% -25.6% -18.2% -27.6% -20.3%vehicle: -36.0% week 8 -22.1% -39.2% -29.9% -45.2% -36.4% #( -47.1% week 12 -27.6% -55.2% -39.3% -59.0% -45.4% 13-19 y (n=173) 20-29 y (n=163) 30+ y (n=80) *p<0.05 vs vehicle; **p<0.01 vs vehicle; ***p<0.001 vs vehicle. there were no significant differences across the 3 age groups at weeks 4, 8, or 12. vehicle: 13-19 y (n=184); 20-29 y (n=189); 30+ y (n=76). multiple imputation method used for missing values. itt, intent-to-treat; ls, least squares. ◾ age-related trends were observed with hyperpigmentation, in which older females had higher mean baseline values; however, mean ratings were still below mild (1) at baseline and did not increase by week 12 figure 4. mean cutaneous safety and tolerability scores in tretinoin-treated females by age group and visit (safety population, pooled) 0 1 scaling m e a n s co re severe3 age 13-19 at baseline age 13-19 at week 12 2 erythema itching burning moderate mild stinging hypopigmentation hyperpigmentation age 20-29 at baseline age 20-29 at week 12 age 30+ at baseline age 30+ at week 12 no imputation for missing values. scores were rated from 0 (none) to 3 (severe). conclusions ◾ in adult and adolescent females with moderate-to-severe acne, tretinoin 0.05% lotion was effective versus vehicle in reducing noninflammatory lesions at week 12; in addition, tretinoin lotion significantly reduced inflammatory lesions in adolescents at week 12 ◾ reductions in acne lesions/egss scores and improvements in qol domains were generally greater in the older age groups (20-29 and 30+ years) compared with younger females (13-19 years), although these differences did not reach statistical significance ◾ tretinoin 0.05% lotion was well tolerated by all age groups references 1. zaenglein al, et al. j am acad dermatol. 2016;74(5):945-973.e933. 2. skroza n, et al. j clin aesthet dermatol. 2018;11(1):21-25. 3. collier cn, et al. j am acad dermatol. 2008;58(1):56-59. 4. tan jk, et al. j cutan med surg. 2008;12(5):235-242. 5. tyring sk, et al. j drugs dermatol. 2018;17(10):1084-1091. author disclosures dr. linda stein gold has served as investigator/consultant or speaker for ortho dermatologics, leo, dermavant, incyte, novartis, abbvie, and lilly. dr. david pariser has served as consultant to atacama therapeutics, bickel biotechnology, biofrontera ag, celgene, dermira, leo, regeneron, sanofi, tdm surgitech, theravida, and ortho dermatologics; investigator for abbott laboratories, almirall, amgen, aobiome, asana biosciences, bickel biotechnology, celgene, dermavant, dermira, eli lilly, leo, menlo therapeutics, merck & co., novartis, novo nordisk a/s, ortho dermatologics, pfizer, regeneron, and stiefel; on advisory board for pfizer; and on the data monitoring board for bms. dr. eric guenin is an employee of ortho dermatologics and may hold stock and/or stock options in its parent company. linda stein gold, md1; david m pariser, md2; eric guenin, pharmd, phd, mph3 1henry ford hospital, detroit, mi; 2virginia clinical research center, norfolk, va; 3ortho dermatologics*, bridgewater, nj *ortho dermatologics is a division of bausch health us, llc. fc17posterskinfixdonaldefficacyandconsumerperception.pdf skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 686 brief article efficacy and safety of tralokinumab in us adults with moderate-to-severe atopic dermatitis: a post-hoc analysis of ecztra3 boni elewski1, matthew zirwas2, azra kurbasic3, shannon schneider4, ami claxton4, jonathan i. silverberg5 1 department of dermatology, the university of alabama at birmingham, birmingham, al 2 probity medical research, columbus, oh 3 leo pharma a/s, ballerup, denmark 4 leo pharma us, madison, nj 5 department of dermatology, the george washington university school of medicine and health sciences, washington, dc abstract background: tralokinumab, a monoclonal antibody that specifically neutralizes interleukin (il)-13, is approved for the treatment of adults with moderate-to-severe atopic dermatitis (ad). tralokinumab was studied in ecztra3 (nct03363854), a randomized, double-blind, multinational, placebo-controlled phase 3 trial of tralokinumab in adults with moderate-to-severe ad. objective: we conducted a post-hoc analysis in the united states (us) subset of ecztra3 patients to inform healthcare practitioners and payers on the efficacy and safety of tralokinumab in the us setting. methods: randomized patient received either 300 mg tralokinumab or placebo every 2 weeks (q2w) in combination with tcs as needed for an initial 16 weeks. thereafter, tralokinumabtreated patients continued with either q2w dosing or q4w+tcs for 16 additional weeks. primary, secondary, and safety endpoints of the ecztra3 us subset were evaluated at 16 and 32 weeks per statistical analyses of the main study (previously published). results: the analytic population included n=63 and n=25, respectively, in the treatment and control arms. at week 16, 37.1% tralokinumab+tcs vs 12.0% placebo+tcs reached investigator’s global assessment (iga) 0/1 (nominal p=0.039); 56.5% of tralokinumab+tcs vs 24.0% placebo+tcs (nominal p=0.012) achieved the eczema area and severity index (easi)-75. secondary, patient-reported outcomes including itch score and health-related quality of life (hrqol) were also improved at week 16 versus baseline, more so for tralokinumab+tcs group. tralokinumab was well tolerated, with an overall safety profile comparable to placebo. conclusions: consistent with the full ecztra3 population, us patients with moderate-tosevere ad treated with tralokinumab+tcs as needed achieved greater symptom relief, reductions in disease severity and improvement of hrqol than placebo+tcs, with comparable safety. skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 687 atopic dermatitis (ad) is a common chronic, inflammatory skin disease characterized by the appearance of recurrent eczematous skin lesions and pruritus. ad is estimated to affect up to 20% of children and 3% of adults worldwide.1 the epidemiology of ad varies regionally,2 which has been partly attributed to environmental factors, socio-economics, urbanization, climate, diet, aeroallergens,3 as well as inter-racial genetic susceptibility.4,5 interleukin 13 (il-13) is a key driver of underlying type 2 inflammation and skinbarrier dysfunction in ad,6 hence us7 and european8 standard of care (soc) includes use of both topical and systemic treatments, topical-corticosteroids (tcs), non-specific immunosuppressants, and biologic treatments targeting cytokines. tralokinumab is a novel, fully human immunoglobulin g4 monoclonal antibody that binds to the il-13 cytokine with high affinity, preventing il-13 receptor interaction and subsequent downstream il-13 signaling.6 tralokinumab is approved by the fda for adults with moderate-to-severe ad whose disease is not adequately controlled by topical prescription therapies or when those therapies are not advisable.9 ecztra3 (nct03363854) is a pivotal, multinational, double-blind, randomized, placebocontrolled, clinical trial with combination topical corticosteroids (+tcs) as needed.10 in the united states, approximately 16.5 million adults have ad11 and 6.6 million experience moderate-to-severe disease.11 given ad epidemiological specificities, evaluating treatment strategies warrants consideration of us-specific study populations. this post-hoc analysis assessed the efficacy and safety of tralokinumab in the us subset of ecztra3 patients. this was a double‐blind, randomized, placebo‐controlled 32‐week trial conducted across 63 sites in europe and north america (see supporting information). after a 2–6‐week screening period, patients were randomized 2:1 to subcutaneous tralokinumab 300 mg every 2 weeks (q2w) +tcs as needed or placebo q2w +tcs as needed, with a 600 mg of tralokinumab or placebo loading dose on day 0.10 primary endpoints included the investigator’s global assessment (iga) score 0/1 (clear/almost clear) and eczema area and severity index (easi)-75. key secondary patient-reported outcome (pro) endpoints included scoring ad (scorad), dermatology life quality index (dlqi) scores and worst daily pruritus numerical rating scale (wdp-nrs) (weekly average). statistical analyses followed the main analyses of ecztra3,10 however, only nominal p values are reported for this posthoc us subgroup evaluation. statistical analysis the difference in response rates between treatment groups was analyzed using the cochran-mantel-haenszel test stratified by baseline severity.12 for binary endpoints, patients who received rescue medication and patients with missing data were imputed as non-responders. the analysis of continuous endpoints used a mixed-effect model for repeated measurements with data collected after rescue medication use or permanent discontinuation of the investigational product treated as missing. we evaluated mean change from baseline (cfb) values using a restricted maximum likelihood-based introduction methods skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 688 repeated-measures approach with the newton raphson algorithm. the model included change from baseline as dependent variable, fixed categorical effects of treatment, baseline disease severity and treatment-by-week interaction, and continuous fixed effects of baseline value and baseline-by-week interaction. within-patient errors were modelled by an unstructured covariance matrix. denominator degrees of freedom were estimated using kenwardroger approximation. all statistical analyses were performed using sas version 9.4 (sas institute inc., cary, nc, usa). a total of 88 us patients were randomized to tralokinumab (n=63) or placebo (n=25), mean age 43 years-old, 69% female, and 55.6% white (table 1). more patients on tralokinumab had moderate disease (65.1% with iga-3) compared with placebo (48.0%); both groups otherwise had comparable baseline characteristics (table 1). more tralokinumab patients achieved iga-0/1 (37.1% vs 12.0% placebo; p=0.039), and easi-75 (56.5% vs 24.0% placebo; p=0.012) at week 16 (figure 1). between group response rates differences were 22.1% (95% confidence interval [ci]: 4.1 40.0 p=0.039) for iga-0/1 and 29.8% for easi-75 (95%ci: 8.5 51.0; p=0.012) tralokinumab patients also displayed a greater reduction in weekly average wdp-nrs ≥4 points at week-16 (42.6%) than placebo (32.0%) with a between group difference of 9.6% (95%ci: –12.9 32.2; p=0.42) (figure 1). the mean (standard error [se]) total week16 scorad total score reduced by 37.6 (2.62) points for tralokinumab versus 17.8 (4.19) for placebo (difference –19.8; 95% ci: –29.7 [–9.9]; p<0.001) (figure 2). mean (se) week-16 dlqi total score was −12.7 (0.82) for tralokinumab compared with −7.9 (1.32) for placebo (difference 4.8; 95%ci: – 7.9 [–1.7]; p=0.003) (figure 2). tralokinumab was well tolerated with an overall safety profile comparable to that of placebo from baseline to week 16 with no serious aes reported (table 2). this post-hoc analysis of us patients in the tralokinumab ecztra3 pivotal trial demonstrated that us patients treated with tralokinumab achieved significant symptom relief, reductions in disease severity, and improvement of health-related quality of life, with comparable safety versus placebo. the us subgroup analysis was warranted given the racial diversity in the us subgroup (44.4% non-white) compared with the full ecztra3 patient population (24.2% nonwhite) and slightly lower baseline disease severity (iga4 severe: 33.3% us patients vs 46.3% overall; median easi score: 21.4 us patients vs 25.5 overall). during the initial 16week trial period, compared with the overall ecztra3 population, the us tralokinumab subgroup showed numerically greater between-group differences versus placebo on week-16 iga-0/1 response, (22.1% us patients vs 12.4% overall), and easi-75 (29.8% us patients vs 20.2% overall), driven by a lower placebo response. between-group differences were also somewhat larger for the us subgroup than in the overall ecztra3 population for improvements on pros (scorad: −19.8 us patients vs −10.9 overall; dlqi: –4.8 us patients vs −2.9 overall).10 finally, safety findings were consistent with the overall ecztra3 study population.10 however, all results discussion skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 689 table 1. ecztra3 us subpopulation patient baseline characteristics. tralokinumab q2w + tcs as needed n=63 placebo q2w + tcs as needed n=25 all randomized n=88 age (years) mean (±sd) 42.3 (17.6) 39.6 (17.3) 41.5 (17.4) sex, n (%) female 41 (65.1) 13 (52.0) 54 (61.4) male 22 (34.9) 12 (48.0) 34 (38.6) race, n (%) white 35 (55.6) 6 (24.0) 41 (46.6) black or african-american 19 (30.2) 10 (40.0) 29 (33.0) asian 5 (7.9) 7 (28.0) 12 (13.6) other 4 (6.3) 2 (8.0) 6 (6.8) disease duration (years) median [iqr] 25 [8.0 – 39.0] 22 [15.0 – 26.0] 24 [10.5 – 38.5] body surface area involvement median [iqr] 33.0 [23.0 – 49.0] 26.0 [22.0 – 48.0] 31.5 [22.0 – 48.5] iga score n (%) grade 3 (moderate) 41 (65.1) 12 (48.0) 53 (60.2) grade 4 (severe) 21 (33.3) 13 (52.0) 34 (38.6) disease severity indices easi score (median [iqr]) 20.5 [17.6 – 30.0] 24.5 [17.0 – 29.3] 21.4 [17.6 – 30.0] scorad score (median [iqr]) 62.5 [52.7 – 75.7] 67.0 [54.6 – 77.7] 63.9 [53.1 – 76.0] weekly average wdp-nrs score (median [iqr]) 8.3 [7.1 – 9.0] 9.0 [7.1 – 9.2] 8.3 [7.1 – 9.1] dlqi score (median [iqr]) 18.0 [12.0 – 22.0] 23.0 [13.0 – 26.0] 18.0 [12.0 – 23.0] skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 690 previous ad treatment, n (%) any 63 (100) 25 (100) 88 (100) topical corticosteroids 63 (100) 24 ( 96.0) 87 (98.9) topical calcineurin inhibitors 20 (31.7) 7 (28.0) 27 (30.7) systemic steroids 39 (61.9) 15 (60.0) 54 (61.4) mycophenolate 2 (3.2) 1 (4.0) 3 (3.4) cyclosporin a 3 (4.8) 3 (12.0) 6 (6.8) methotrexate 5 (7.9) 4 (16.0) 9 (10.2) azathioprine 1 (1.6) 0 1 (1.1) phototherapy 12 (19.0) 5 (20.0) 17 (19.3) history of allergy, n (%) asthma 38 (60.3) 23 (92.0) 60 (56.8) food allergy 20 (31.7) 9 (36.0) 29 (32.9) hay fever 35 (55.6) 10 (40.0) 45 (51.1) dlqi, dermatology life quality index; easi, eczema area and severity index; iga, investigator’s global assessment; iqr, interquartile range; nrs, numeric rating scale; scorad, scoring atopic dermatitis; wa: weekly average; wdp, worst daily pruritus. skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 691 figure 1. week 16 response rates on iga 0/1, easi-75, nrs>=4 in ecztra3 us subpopulation. δ: difference in response rates calculated based on stratification by the baseline iga using the cochranmantel-haenszel test estimate. easi, eczema area and severity index; iga-0/1, investigator’s global assessment score of 0 or 1; q2w, every 2 weeks; q4w, every 4 weeks; tcs, topical corticosteroids; wdp nrs, worst daily pruritus numeric rating scale. skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 692 figure 2. week 16 change from baseline in scorad and dlqi adjusted means in ecztra3 us subpopulation. δ: difference in total score and 95% confidence interval. dlqi, dermatology life quality index; scorad, scoring atopic dermatitis. skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 693 table 2. summary of adverse events during initial 16-week treatment and response rates at weeks 16 in ecztra3 us subpopulation.* tralokinumab q2w + tcs n=62; pye=17.87 placebo q2w + tcs n=25; pye=7.5 adverse events during initial 16 weeks of study: n (%) n (%) at least one ae 40 (64.5) 16 (64.0) at least one serious ae 0 1 (4.0) ae leading to withdrawal from trial 2 (3.2) 0 severity mild 34 (54.8) 12 (48.0) moderate 11 (17.7) 6 (24.0) severe 0 1 (4.0) outcome not recovered/not resolved 13 (21.0) 3 (12.0) recovering/resolving 1 (1.6) 2 (8.0) recovered/resolved 38 (61.3) 13 (52.0) recovered/resolved with sequalae 1 (1.6) 0 *among patients with iga score of 0/1 at week 16 and easi-75 among patients with easi-75 at week 16. ae, adverse event; pye, person years of exposure; q2w, every 2 weeks; tcs, topical corticosteroids skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 694 results must be considered in light of the limited size of the us subgroup. in a subset analysis of us patients with moderate-to-severe ad from the pivotal trial, ecztra3, more patients treated with tralokinumab+tcs as needed achieved improvements in outcomes compared with placebo+tcs as needed. tralokinumab+tcs as needed was also well tolerated. these results are consistent with the overall ecztra3 study population results. clinical trial number: nct03363854 acknowledgements: the authors would like to thank all investigators and patients who participated in the ecztra3 study. conflict of interest disclosures: boni elewski reports receiving honoraria as a consultant for boehringer ingelheim, bristol-myers squibb, celgene, leo pharma, lilly, menlo therapeutics, novartis, pfizer, sun, valeant (ortho dermatologics), and verrica; and has received research funding from abbvie, anaptysbio, boehringer ingelheim, bristolmyers squibb, celgene, incyte, leo pharma, lilly, menlo therapeutics, merck, novartis, pfizer, regeneron, sun, valeant (ortho dermatologics), and vanda. matthew zirwas is a consultant, investigator, and/or speaker for abbvie, all free care/sun, anaptys bio, arcutis, bausch health, cara, concert, dermavant, edessa biotech, eli lilly and company, epi health, fit bit, galderma, genentech, incyte, leo pharma, level-ex, l’oréal, luum, menlo, novartis, oculus, ortho derm, peloton, pfizer, regeneron, sanofi, trevi, and ucb, is a part owner of asepticmd, and has worked with leo pharma and other companies with atopic dermatitis drugs that have received fda approval or are expected to receive fda approval in the next year. azra kurbasic, shannon schneider, and ami claxton are employees of leo pharma. jonathan i. silverberg reports personal fees from abbvie, afyx, anaptysbio, aobiome, arena, asana, aslan, biomx, bluefin, bodewell, boehringer ingelheim, celgene, connect biopharma, dermavant, dermira, ds biopharma, eli lilly, galderma, glaxosmithkline, incyte, kiniksa, kymab, leo pharma, luna, menlo, novartis, pfizer, rapt, realm, regeneron, and sanofi genzyme, grants and/or personal fees from galderma, glaxosmithkline and pfizer, and stock/stock options from abbvie, arcutis, and eli lilly. funding: the trial was sponsored by leo pharma a/s (ballerup, denmark). medical writing support was provided by gauri saal, ma economics, medistrava (an inizio company), london, uk and funded by leo pharma us, madison, nj. corresponding author: boni elewski, md the university of alabama at birmingham department of dermatology 500 22nd st. s floor 3, birmingham, al 35322 email: belewski@uabmc.edu references: 1. nutten s. atopic dermatitis: global epidemiology and risk factors. annals of nutrition and metabolism. 2015;66(suppl 1)(suppl. 1):8-16. doi:10.1159/000370220 2. beasley r, of asthma tis. worldwide variation in prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and atopic eczema: isaac. the lancet. 1998;351(9111):1225-1232. 3. lee bw, detzel pr. treatment of childhood atopic dermatitis and economic burden of illness in asia pacific countries. annals of nutrition and metabolism. 2015;66(suppl 1)(suppl. 1):18-24. doi:10.1159/000370221 4. garrett jpd, hoffstad o, apter aj, margolis dj. racial comparison of filaggrin null mutations in asthmatic patients with atopic dermatitis in a us population. journal of allergy and clinical immunology. 2013/11/01/ 2013;132(5):1232-1234. doi:https://doi.org/10.1016/j.jaci.2013.07.005 5. palmer cna, irvine ad, terron-kwiatkowski a, et al. common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. nature genetics. 2006/04/01 2006;38(4):441-446. doi:10.1038/ng1767 6. bieber t. interleukin-13: targeting an underestimated cytokine in atopic dermatitis. allergy. jan 2020;75(1):54-62. doi:10.1111/all.13954 7. sidbury r, tom wl, bergman jn, et al. guidelines of care for the management of atopic dermatitis: section 4. prevention of conclusion https://doi.org/10.1016/j.jaci.2013.07.005 skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 695 disease flares and use of adjunctive therapies and approaches. j am acad dermatol. dec 2014;71(6):1218-33. doi:10.1016/j.jaad.2014.08.038 8. wollenberg a, barbarot s, bieber t, et al. consensus-based european guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children: part ii. j eur acad dermatol venereol. jun 2018;32(6):850-878. doi:10.1111/jdv.14888 9. u.s. food and drug administration. adbry™ (tralokinumab-ldrm) injection, for subcutaneous use. accessed 12 july, 2022. https://mc-df05ef79-e68e-4c65-8ea2953494-cdn-endpoint.azureedge.net//media/corporatecommunications/us/therape utic-expertise/ourproduct/adbrypi.pdf?rev=65a4030a71404731 98c24e795b9c19f1 10. silverberg ji, toth d, bieber t, et al. tralokinumab plus topical corticosteroids for the treatment of moderate-to-severe atopic dermatitis: results from the double-blind, randomized, multicentre, placebo-controlled phase iii ecztra 3 trial. br j dermatol. mar 2021;184(3):450-463. doi:10.1111/bjd.19573 11. chiesa fuxench zc, block jk, boguniewicz m, et al. atopic dermatitis in america study: a cross-sectional study examining the prevalence and disease burden of atopic dermatitis in the us adult population. j invest dermatol. mar 2019;139(3):583-590. doi:10.1016/j.jid.2018.08.028 12. yu b, gastwirth jl. a method of assessing the sensitivity of the cochran-mantelhaenszel test to an unobserved confounder. philos trans a math phys eng sci. jul 13 2008;366(1874):2377-88. doi:10.1098/rsta.2008.0030 https://mc-df05ef79-e68e-4c65-8ea2-953494-cdn-endpoint.azureedge.net/-/media/corporatecommunications/us/therapeutic-expertise/our-product/adbrypi.pdf?rev=65a4030a7140473198c24e795b9c19f1 https://mc-df05ef79-e68e-4c65-8ea2-953494-cdn-endpoint.azureedge.net/-/media/corporatecommunications/us/therapeutic-expertise/our-product/adbrypi.pdf?rev=65a4030a7140473198c24e795b9c19f1 https://mc-df05ef79-e68e-4c65-8ea2-953494-cdn-endpoint.azureedge.net/-/media/corporatecommunications/us/therapeutic-expertise/our-product/adbrypi.pdf?rev=65a4030a7140473198c24e795b9c19f1 https://mc-df05ef79-e68e-4c65-8ea2-953494-cdn-endpoint.azureedge.net/-/media/corporatecommunications/us/therapeutic-expertise/our-product/adbrypi.pdf?rev=65a4030a7140473198c24e795b9c19f1 https://mc-df05ef79-e68e-4c65-8ea2-953494-cdn-endpoint.azureedge.net/-/media/corporatecommunications/us/therapeutic-expertise/our-product/adbrypi.pdf?rev=65a4030a7140473198c24e795b9c19f1 https://mc-df05ef79-e68e-4c65-8ea2-953494-cdn-endpoint.azureedge.net/-/media/corporatecommunications/us/therapeutic-expertise/our-product/adbrypi.pdf?rev=65a4030a7140473198c24e795b9c19f1 acknowledgements: medical writing support was provided by prescott medical communications group (chicago, il) with financial support from ortho dermatologics; ortho dermatologics is a division of bausch health us, llc | presented at winter clinical dermatology conference 2020 • january 17-22, 2020 • kohala coast, hi synopsis ◾ psoriasis is a chronic, immune-mediated disease that can have frequent exacerbations and remissions1 ◾ treatment decisions for psoriasis can be complex, with considerations including patient and provider preferences, patient goals, psychosocial factors, comorbidities, and financial burden2 ◾ topicals are considered first-line therapy for mild disease3 and are having an increasing role in moderateto-severe psoriasis as an integral part of combination therapy methods ◾ the national psoriasis foundation, on behalf of ortho dermatologics, deployed an online survey developed by ortho dermatologics to the patient community through the npf mystudies e-newsletter ◾ the survey was available for approximately 2 months starting in the first quarter of 2018 results ◾ the survey included a total of 314 respondents, with a 99.4% completion rate ◾ of the respondents, 86.9% were diagnosed with psoriasis >5 years ago (table 1) ◾ over three-fourths of respondents reporting having the following body parts typically affected by plaque psoriasis: scalp, arms, and legs (table 1) ◾ multiple treatments were common in this group, with 61.6% of patients having used ≥5 treatments or products; 16.1% had used more than 15 (table 1) treatment of psoriasis: a survey on patient preference and satisfaction figure 1. previous and current treatments 100% 80% 60% 40% 20% 0% 100.0% 87.1% topical medications 54.0% 15.8% phototherapy 41.7% 12.2% oral medications 38.2% 21.2% biologic medications 14.2% 8.4% other 2.3% 5.5% i’m not currently using anything previous treatments current treatments p e rc e n ta g e o f p a rt ic ip a n ts questions: what, if anything, have you used in the past to treat your plaque psoriasis (select all that apply)? what, if anything, are you currently using to treat your plaque psoriasis (select all that apply)? a total of 0.6% of respondents replied “don’t know” for the question on previous treatments. figure 2. openness to trying new treatments somewhat open (34.3%) 93.2% open to trying new treatments very open (25.2%) not very open (5.2%) extremely open (33.7%) not at all open (1.6%) question: how open are you to trying new treatments for your plaque psoriasis? figure 3. satisfaction with current psoriasis treatment (a) and reasons for lack of satisfaction (b) extremely (1.9%) a. overall satisfaction with treatment b. reasons for lack of treatment satisfaction very (11.7%) somewhat (39.8%) not very (31.1%) not at all (15.5%) 8.9% 4.9% 4.1% 74.8% 5.7% 1.6% my treatment is not effective enough i am concerned about side effects i am concerned about long term safety my treatment isn’t easy to use i don’t like how often i need to use my treatment other questions: overall, how satisfied are you with your current plaque psoriasis treatment? which, if any, of the following reasons explains why you are not satisfied with your current plaque psoriasis treatment? figure 4. respondents that would have continued topical treatment if it was effective (n=92) i would have continued using the topical (54.3%) i would have still started a systemic or biologic (28.3%) i don’t know (14.1%) not applicable (3.3%) of the 92 participants that had previously used topical treatment and were currently taking a biologic or systemic treatment, most (n=73) were also still using topical treatment. question: if your topical treatment had been more effective, would you have continued to use it instead of using a systemic or biologic, or would you have still started a systemic or biologic? ◾ conclusions ◾ most survey respondents had moderate-tosevere psoriasis with a duration of over 5 years ◾ all respondents had used topical treatments in the past, and the vast majority were currently using topicals to treat their psoriasis ◾ patient satisfaction was low, with lack of effectiveness being the main driver of dissatisfaction ◾ of individuals who did not achieve sufficient response to topical treatment, over half would have continued to use their topical treatment over starting a systemic/biologic if the topical had been more effective ◾ these survey results suggest that patients are extensively using topical treatments to control their psoriasis, and that topical treatments, if more effective, would be preferred by most patients over systemic or biologic treatments references 1. nestle fo, et al. n engl j med. 2009;361(5):496-509. 2. visconti, et al. j comp eff res. 2019;8(12):947-949. 3. menter, et al. j am acad dermatol. 2009;60(4):643-659. author disclosures dr. lawrence green has served as a speaker, consultant, and/or investigator for: arcutis, abbvie, amgen, celgene, dermavant, jannsen, lilly, mc2, novartis, ortho dermatologics, sienna, sunpharma, ucb. dr. april armstrong has served as a research investigator and/or consultant to abbvie, janssen, lilly, leo, novartis, ucb, ortho dermatologics, dermira, sanofi, regeneron, bms, dermavant, and modernizing medicine. dr. craig f teller has nothing to disclose. dr. stacie bell is an employee of the national psoriasis foundation. dr. tina lin is an employee of ortho dermatologics and may hold stock and/or stock options in its parent company. table 1. respondent characteristics % of respondents survey respondents (n=314) first diagnosed with plaque psoriasis within past year 1.3 1 – 3 years ago 4.5 3 – 5 years ago 7.4 >5 years ago 86.9 severity of disease (self-classified) mild 15.8 moderate 53.1 severe 30.9 body parts commonly affected by psoriasis (>50% respondents) scalp 78.5 arms 75.6 legs 75.2 body 61.4 total number of treatments ever used 1 2.3 2 – 5 36.1 5 – 10 31.0 10 – 15 14.5 >15 16.1 ◾ all patients had previously used topical medication(s), with current therapies primarily comprising topicals (87.1%) and biologics (21.2%; figure 1) ◾ nearly all respondents (93.2%) were open to trying new treatments (figure 2; blue regions) ◾ only 13.6% of respondents were very or extremely satisfied with their current plaque psoriasis treatment, with the lack of satisfaction primarily due to treatment not being effective enough (figure 3) ◾ of the 92 participants that had previously been on topical treatment and were currently on a systemic or biologic, over half stated that they would have preferred continuing their topical instead of starting a systemic/biologic treatment if their treatment was more effective (figure 4) lawrence green, md1; april armstrong, md, mph2; craig f teller, md3; stacie bell, phd4; tina lin, pharmd5 1george washington university school of medicine, washington, dc; 2keck school of medicine, university of southern california, los angeles, ca; 3bellaire dermatology associates, houston, tx; 4national psoriasis foundation; 5ortho dermatologics*, bridgewater, nj *ortho dermatologics is a division of bausch health us, llc. 101102042_cobi_pop_pk_l1a presented at the winter clinical dermatology conference; january 13-18, 2023; kohala coast, hawaii copies of this poster obtained through this qr code, are for your personal use only and may not be reproduced without permission from the authors. copyright © 2023. all rights reserved. background • skin pain is a commonly reported and burdensome symptom in patients with atopic dermatitis (ad)1 • abrocitinib is an oral once-daily, janus kinase 1–selective inhibitor approved for the treatment of patients with moderate-to-severe ad2,3 objective • to assess the efficacy of abrocitinib on skin pain in adult and adolescent patients with moderate-to-severe ad methods • data were analyzed from trials with abrocitinib as monotherapy (pooled phase 2b trial [age 18-75 years] and phase 3 trials jade mono-1 [nct03349060] and mono-2 [nct03575871; both age ≥12 years]) or in combination with topical therapy (phase 3 trials jade compare [nct03720470; age ≥18 years] and jade teen [nct03796676; age 12-17 years]) • patients received oral abrocitinib 200 mg or 100 mg or placebo once daily – jade compare also included an active-control arm (dupilumab 300 mg administered subcutaneously every other week) • patients rated their skin pain score from 0 (not painful) to 10 (extremely painful) over a 24-hour period using the pruritus and symptoms assessment for atopic dermatitis (psaad) instrument4 • least squares mean change from baseline in psaad item # 2 (“how painful was your skin over the past 24 hours?”) was assessed in: – adult and adolescent patients from the pooled monotherapy trials • results from jade compare and jade teen have been presented previously5 – a subset of patients across the trials who were classified as nonresponders per investigator’s global assessment (iga) • iga response was defined as achieving an iga score of 0/1 and a ≥2-point improvement from baseline results patients • baseline demographics for patients in the pooled monotherapy, jade compare, and jade teen trials are shown in table 1 table 1. baseline characteristics (full analysis set) pooled monotherapya n=942 jade compare n=837 jade teen n=285 age, y mean ± sd median (iqr) 35.0 ± 15.9 na 37.7 ± 14.7 na na 15.0 (13.0-17.0) age <18 years of age, n (%) 124 (13.2) 0 (0.0) 284 (99.6)b duration of disease, y, mean ± sd 23.0 ± 15.5 22.7 ± 15.4 10.0 ± 5.2 easi score, mean ± sd 28.8 ± 12.7 30.9 ± 12.8 29.9 ± 12.5 pp-nrs total score, mean ± sd 7.0 ± 1.9 7.3 ± 1.7 7.0 ± 1.8 dlqi total score, mean ± sd 14.6 ± 6.9 15.7 ± 6.6 na cdlqi total score, mean ± sd 12.7 ± 6.0 na 14.0 ± 6.6 hads anxiety score, mean ± sd 6.1 ± 4.1 5.3 ± 3.8 5.5 ± 4.0 hads depression score, mean ± sd 4.3 ± 3.8 3.9 ± 3.5 3.6 ± 3.2 psaad item # 2 score, mean ± sd 5.6 ± 2.5f 5.6 ± 2.6g 5.0 ± 2.6h cdlqi, children’s dermatology life quality index; dlqi, dermatology life quality index; easi, eczema area and severity index; hads, hospital anxiety and depression scale; iqr, interquartile range; na, not applicable; pp-nrs, peak pruritus numerical rating scale (used with permission from regeneron pharmaceuticals, inc., and sanofi); psaad, pruritus and symptoms assessment for atopic dermatitis. apooled monotherapy population includes patients from the phase 2b and the phase 3 jade mono-1 and jade mono-2 trials. b1 patient in the placebo group was enrolled at age 18 years, which was a protocol deviation. fn=802. gn=780. hn=254. efficacy of abrocitinib in the pooled monotherapy population • abrocitinib monotherapy improved skin pain in both adult and adolescent patients as early as week 2, and improvements were maintained through week 12 (figure 1) – improvements with abrocitinib were greater than placebo at all evaluated time points and were dose dependent figure 1. change from baseline to week 12 in skin pain in (a) adult and (b) adolescent patients in the pooled monotherapy population 0.5 0.0 −2.5 −4.5 −2.0 −4.0 −1.5 −3.5 −1.0 −0.5 −3.0 week a 128420 *weeks 2, 4, 8, 12 (vs placebo) *weeks 2, 4, 8, 12 (vs placebo) ls m c fb in p s a a d ite m # 2 (9 5% c i) 0.5 0.0 −2.5 −4.5 −2.0 −4.0 −1.5 −3.5 −1.0 −0.5 −3.0 week b 128420 *weeks 2, 4, 8, 12 (vs placebo) *weeks 2, 4, 8, 12 (vs placebo) ls m c fb in p s a a d ite m # 2 (9 5% c i) abrocitinib 200 mg qd (n=271) placebo (n=148) abrocitinib 100 mg qd (n=268) abrocitinib 200 mg qd (n=46) placebo (n=23) abrocitinib 100 mg qd (n=46) cfb, change from baseline; lsm, least squares mean; psaad, pruritus and symptoms assessment for atopic dermatitis; qd, once daily. *nominal p<0.05 for abrocitinib versus placebo. pooled monotherapy population includes patients from the phase 2b, and phase 3 jade mono-1 and jade mono-2 trials. results from jade compare and jade teen have been presented previously.5 efficacy of abrocitinib treatment in nonresponders per iga • improvements in skin pain were observed among patients classified as nonresponders per iga after treatment with abrocitinib as monotherapy (figure 2a) or in combination with topical treatment in jade compare (figure 2b) and jade teen (figure 2c) – skin pain improvement was seen as early as week 1 in a dose-dependent manner across all studies – improvements were maintained through week 12 or week 16 of treatment abrocitinib reduces skin pain in adolescent and adult patients with moderate-to-severe atopic dermatitis jacob p. thyssen,1 anthony bewley,2 sonja ständer,3 carla castro,4 laurent misery,5 brian s. kim,6 pinaki biswas,7 gary chan,8 daniela e. myers,9 melissa watkins,7 justine alderfer,9 erman guler,10 jonathan i. silverberg11 1bispebjerg hospital, university of copenhagen, copenhagen, denmark; 2barts health nhs trust, london, united kingdom; 3center for chronic pruritus, münster university hospital, munster, germany; 4hospital universitario austral, pilar, argentina; 5university hospital of brest, brest, france; 6washington university school of medicine, st. louis, mo, usa; 7pfizer inc., new york, ny, usa; 8pfizer inc., groton, ct, usa; 9pfizer inc., collegeville, pa, usa; 10pfizer inc., istanbul, turkey; 11the george washington university school of medicine and health sciences, washington dc, usa figure 2. change from baseline to week 12/16 in skin pain among nonresponders per igaa in (a) the monotherapy pool,b (b) jade compare, and (c) jade teen 0.5 0.0 −2.5 −4.0 −2.0 −1.5 −3.5 −1.0 −0.5 −3.0 week c 128 9 10 1131 5 6 7420 *weeks 1–7, 9, 11, 12 (vs placebo) *weeks 1–12 (vs placebo) ls m c fb in p s a a d ite m # 2 (9 5% c i) 0.5 0.0 −2.5 −4.0 −2.0 −1.5 −3.5 −1.0 −0.5 −3.0 week a 128 9 10 1131 5 6 7420 *weeks 1–12 (vs placebo) *weeks 1–12 (vs placebo) ls m c fb in p s a a d ite m # 2 (9 5% c i) 0.5 0.0 −2.5 −4.0 −2.0 −1.5 −3.5 −1.0 −0.5 −3.0 week b 1615131198 10 12 1431 5 6 7420 *weeks 16 (vs placebo) *weeks 2–16 (vs placebo) ls m c fb in p s a a d ite m # 2 (9 5% c i) abrocitinib 200 mg qd (n=150) placebo (n=154) abrocitinib 100 mg qd (n=208) abrocitinib 200 mg qd (n=78) placebo (n=93) abrocitinib 100 mg qd (n=91) abrocitinib 200 mg qd (n=32) placebo (n=56) abrocitinib 100 mg qd (n=41) cfb, change from baseline; lsm, least squares mean; psaad, pruritus and symptoms assessment for atopic dermatitis; qd, once daily. *nominal p<0.05 for abrocitinib vs placebo. aiga response was defined as achieving an iga score of 0/1 and a ≥2-point improvement from baseline. bpooled monotherapy population includes patients from the phase 2b and the phase 3 jade mono-1 and jade mono-2 trials. conclusions • abrocitinib as monotherapy or in combination with topical therapy rapidly and consistently reduced skin pain in adult and adolescent patients with moderate-to-severe ad, including those who did not achieve iga response references 1. vakharia pp et al. ann allergy asthma immunol. 2017;119:548-552.e3 2. cibinqo (abrocitinib). prescribing information. pfizer labs; january 2022. 3. cibinqo (abrocitinib). summary of product characteristics. european medicines agency; december 17, 2021. 4. hall r et al. dermatol ther (heidelb). 2021;11:221-233. 5. thyssen j et al. presented at: 3rd annual revolutionizing atopic dermatitis virtual conference; december 11-13, 2021. abstract 639. acknowledgments editorial/medical writing support under the guidance of authors was provided by renata cunha, pharmd, and jaya kolipaka at apothecom, san francisco, ca, usa, and was funded by pfizer inc., new york, ny, usa, in accordance with good publication practice (gpp 2022) guidelines (ann intern med. 2022; 10.7326/m22-1460). this study was sponsored by pfizer inc. previously presented at the 4th annual revolutionizing atopic dermatitis conference (rad); april 9-11, 2022; hybrid, baltimore, md. disclosures jpt is an advisor for pfizer inc., abbvie, almirall, arena pharmaceuticals, aslan pharmaceuticals, coloplast, eli lilly and company, om pharma, leo pharma, regeneron, sanofi genzyme, and union therapeutics and a speaker for pfizer inc., abbvie, almirall, eli lilly and company, leo pharma, regeneron, and sanofi genzyme and has received research grants from pfizer inc., regeneron, and sanofi genzyme. ab reports consultancy for and travel grants from abbvie, almirall, eli lilly and company, galderma, janssen, leo pharma, novartis, sanofi, and ucb. sst is an investigator for dermasence, galderma, kiniksa, menlo therapeutics, novartis, sanofi, trevi therapeutics, and vanda; roles as a member of scientific advisory boards, consultant, and/or speaker for pfizer inc., abbvie, almirall, beiersdorf, bellus health, benevolent, bionorica, cara, clexio, escient, galderma, grünenthal, kiniksa, leo pharma, eli lilly and company, menlo therapeutics, p.g. unna academy, sanofi, trevi therapeutics, and vifor. cc is a principal or sub-investigator for pfizer inc., abbvie, boehringer ingelheim, eli lilly and company, novartis, and sanofi and a speaker and/or advisor for pfizer inc., abbvie, andromaco, cerave, galderma, isdin, la roche-posay, novartis, and sanofi. lm is an investigator for pfizer inc., abbvie, galderma, kiniksa, eli lilly and company, menlo therapeutics, novartis, sanofi, and trevi therapeutics and a consultant for abbvie, beiersdorf, clexio, galderma, eli lilly and company, menlo therapeutics, novartis, sanofi, sienna biopharmaceuticals, and trevi therapeutics. bsk is a consultant and advisor for pfizer inc., abbvie, boehringer ingelheim, cara therapeutics, kiniksa, menlo therapeutics, and sanofi-regeneron; has received research grants from cara therapeutics, celgene, and leo pharma; and is founder and stockholder in nuogen pharma. pb, gc, dem, mw, ja, and eg are employees and shareholders of pfizer inc. jis served as an investigator for celgene, eli lilly and company, f. hoffmann-la roche, menlo therapeutics, realm therapeutics, regeneron, and sanofi; as a consultant for pfizer inc., abbvie, anacor, anaptysbio, arena pharmaceuticals, dermavant, dermira, eli lilly and company, galderma, glaxosmithkline, glenmark, incyte, kiniksa pharmaceuticals, leo pharma, menlo therapeutics, novartis, realm therapeutics, regeneron, and sanofi; and as a speaker for regeneron and sanofi. efficacy of ritlecitinib (pf-06651600) in patients with alopecia totalis and alopecia universalis: post hoc analysis of the allegro phase 2b/3 study xingqi zhang,1 nina magnolo,2 masato mizuashi,3 natasha mesinkovska,4 jerry shapiro,5 fan zhang,6 urs kerkmann,7 ernest law,8 robert wolk,6 gregor schaefer7 1the first affiliated hospital, sun yat-sen university, guangzhou, china; 2university hospital münster, münster, germany; 3tohoku university graduate school of medicine, sendai, japan; 4school of medicine, university of california, irvine, ca, usa; 5new york university grossman school of medicine, new york, ny, usa; 6pfizer inc, groton, ct, usa; 7pfizer pharma gmbh, berlin, germany; 8pfizer inc, new york, ny, usa background • alopecia areata (aa) is an autoimmune disease that has an underlying immuno-inflammatory pathogenesis and is characterized by nonscarring hair loss ranging from small patches to complete scalp, face, and/or body hair loss1 • spontaneous hair regrowth can occur in aa; however, it is unlikely to occur in extensive forms of aa, including alopecia totalis (at; complete loss of scalp hair) and alopecia universalis (au; complete loss of scalp, face, and body hair)2 • the severity of alopecia tool (salt) assesses the extent of scalp hair loss with scores ranging from 0 (no scalp hair loss) to 100 (complete scalp hair loss); patients with at and au have a salt score of 1003 • ritlecitinib, an oral jak3/tec inhibitor, demonstrated efficacy and safety in patients aged ≥12 years with aa in the allegro phase 2b/3 trial (nct03732807)4 objective • to evaluate the efficacy of ritlecitinib at weeks 24 and 48 in patients with at and au in the allegro phase 2b/3 study methods study design • the allegro phase 2b/3 trial was an international, randomized, double-blind, placebo-controlled, combined dose-ranging and pivotal phase 2b/3 study (figure 1) • patients received once daily ritlecitinib (± a 4-week 200-mg daily loading dose): 200/50 mg, 200/30 mg, 50 mg, 30 mg, 10 mg (10 mg assessed for dose ranging only), or placebo for 24 weeks • during the 24-week extension, ritlecitinib groups continued receiving their 50, 30, or 10 mg maintenance doses, and patients initially assigned to placebo switched to 200/50 or 50 mg daily key eligibility criteria • patients aged ≥12 years with a diagnosis of aa and ≥50% scalp hair loss, including those with at and au, and a current aa episode duration of 6 months to 10 years figure 1. study design rit 200 mg qd rit 200 mg qd rit 50 mg qd rit 30 mg qd rit 10 mg qd placebo placebo rit 50 mg qd rit 30 mg qd rit 50 mg qd rit 30 mg qd rit 10 mg qd placebo placebo rit 50 mg qd rit 30 mg qd rit 50 mg qd rit 30 mg qd rit 10 mg qd rit 200/50 mg qd rit 50 mg qd placebo-controlled (24 weeks) study week extension (24 weeks) maintenance (20 weeks) loading (4 weeks) bl 2 4 8 12 18 26 28 34 40 4824 s cr ee ni ng r an do m iz at io n screening and randomization (35 days) n=132 n=66 n=65 n=63 n=130 n=132 n=130 bl, baseline; qd, once daily; rit, ritlecitinib. outcomes • this study assessed the proportion of patients in each subgroup with response based on a salt score of ≤20 (≤20% scalp without hair) and a patient global impression of change (pgi-c) response of “moderately improved” or “greatly improved” at weeks 24 and 48 pgi-c is a self-reported, single-item scale on which patients rate the improvement or worsening of aa compared with aa at the start of the study, using a scale of 7 responses ranging from “greatly improved” to “greatly worsened” statistical analysis • in this post hoc analysis, patients were stratified by type of aa at baseline and were divided into 4 subgroups: at/au, at, au, and non-at/non-au the at/au subgroup comprised all patients with a salt score of 100 (complete scalp hair loss) at baseline patients in the at or au groups had a salt score of 100 at baseline and a clinical diagnosis of at or au, respectively, by the investigator • descriptive analyses were used to evaluate the proportion of patients with salt ≤20 and pgi-c response by at/au status • 95% cis were calculated based on normal approximation efficacy by at/au status at weeks 24 and 48 • in all aa subgroups, salt ≤20 response rates generally increased between weeks 24 and 48 (figure 2) across all ritlecitinib treatment groups (200/50 mg, 200/30 mg, 50 mg, 30 mg), salt ≤20 response rates were highest in the non-at/non-au group at weeks 24 and 48 placebo response rates were low across all subgroups at week 24; a substantial proportion of patients who switched to ritlecitinib 200/50 or 50 mg had a salt ≤20 response by week 48 at week 48, the proportion of patients with a salt ≤20 response was generally similar across the at/au, at, and au subgroups • higher proportions of patients with non-at/non-au had a pgi-c response of "moderately improved" or "greatly improved" in all treatment groups vs patients with at/au, at, or au at week 24, and response rates generally improved through week 48 (figure 3) at week 48, up to 49%, 50%, and 64% of patients had a pgi-c response in the at/au, at, and au subgroups, respectively, vs up to 73% in the non-at/non-au subgroup presented at the 2022 fall clinical dermatology conference; october 20 23, 2022; las vegas, nevada references 1. islam n, et al. autoimmun rev. 2015;14:81-89. 2. delamere fm, et al. cochrane database syst rev. 2008;16:cd004413. 3. olsen ea, et al. j am acad dermatol. 2018;79:470-478. 4. king b, et al. presented at: eadv 2021. disclosures this study was sponsored by pfizer inc. f.z., u.k., e.l., r.w., and g.s. are employees of pfizer and hold stock or stock options in pfizer. x.z. declares no conflicts of interest. n.m. reports honoraria for participation in advisory boards from and being a speaker and/or for consultant for abbvie, almirall, bms, boehringer ingelheim, celgene, eli lilly, janssen, leo pharma, novartis, pfizer, and ucb. m.m. is a principal clinical trial investigator for pfizer. n.m. has provided professional services for abbvie, arcutis, arena, bms, concert, galderma, merz, eli lilly, kadmon, novartis, and pfizer and has received honoraria from eli lilly, pfizer, nutrafol, concert, and arena. j.s. provides consultancy for pfizer and eli lilly and is a clinical trial investigator for pfizer. third-party medical writing assistance, provided by health interactions, inc, was funded by pfizer inc. results • of the 718 patients randomized, 151 (21%) had at and 147 (20%) had au; patients with at and au were evenly distributed across treatment groups (table 1) table 1. baseline characteristics ritlecitinib qd 200/50 mg (n=132) 200/30 mg (n=130) 50 mg (n=130) 30 mg (n=132) 10 mg (n=63) placebo* (n=131) age mean (sd), years 34.5 (15.0) 33.7 (13.8) 32.4 (13.4) 33.7 (14.8) 34.3 (13.9) 34.0 (15.0) 12-17 years, n (%) 20 (15.2) 19 (14.6) 18 (13.8) 20 (15.2) 9 (14.3) 19 (14.5) ≥18 years, n (%) 112 (84.8) 111 (85.4) 112 (86.2) 112 (84.8) 54 (85.7) 112 (85.5) female, n (%) 81 (61.4) 85 (65.4) 71 (54.6) 80 (60.6) 43 (68.3) 86 (65.6) white, n (%) 92 (69.7) 90 (69.2) 79 (60.8) 91 (68.9) 42 (66.7) 94 (71.8) type of aa, n (%) at/au† 60 (45.5) 60 (46.2) 60 (46.2) 61 (46.2) 29 (46.0) 60 (45.8) at‡ 25 (18.9) 34 (26.2) 30 (23.1) 26 (19.7) 12 (19.0) 24 (18.3) au‡ 26 (19.7) 21 (16.1) 24 (18.5) 29 (22.0) 13 (20.6) 34 (26.0) non-at/non-au 72 (54.5) 70 (53.8) 70 (53.8) 71 (53.8) 34 (54.0) 71 (54.2) baseline salt score, mean (sd) all patients 90.3 (15.1) 90.5 (14.3) 90.3 (14.7) 90.0 (15.1) 88.3 (16.9) 93.0 (11.5) non-at/non-au† 82.2 (16.5) 82.4 (15.4) 82.0 (15.9) 81.5 (16.3) 78.3 (17.6) 87.0 (12.9) duration of current aa episode, mean (sd), years 3.4 (2.93) 3.4 (2.89) 3.2 (2.67) 3.6 (2.82) 3.3 (2.65) 3.2 (2.65) aa, alopecia areata; at, alopecia totalis; au, alopecia universalis; qd, once daily; salt, severity of alopecia tool. *patients received placebo for 24 weeks and then switched to ritlecitinib 200/50 mg or 50 mg qd. †all patients in the at/au category had a salt score of 100 at baseline. this subgroup includes patients who had received a clinical diagnosis of at or au plus those with a baseline salt score of 100 without a clinical diagnosis of at or au. ‡patients in the at or au category had a salt score of 100 at baseline and received a clinical diagnosis of at or au, respectively, by the investigator. patients with at or au were included in the at/au category. figure 2. response based on salt ≤20 at weeks 24 and 48 by at/au status aa, alopecia areata; at, alopecia totalis; au, alopecia universalis; qd, once daily; salt, severity of alopecia tool. percentages and error bars (95% cis) are shown for salt ≤20 response at week 48. figure 3. response based on pgi-c score* at weeks 24 and 48 by at/au status aa, alopecia areata; at, alopecia totalis; au, alopecia universalis; pgi-c, patient global impression of change; qd, once daily. *pgi-c response was defined as “moderately improved” or “greatly improved”. percentages and error bars (95% cis) are shown for pgi-c response at week 48. conclusions • ritlecitinib demonstrated clinical and patient-reported efficacy across all aa subgroups, including in patients with more extensive forms of aa (at and au) • higher salt ≤20 response rates were observed in patients with less extensive aa (non-at/non-au) than in patients with at/au, at, or au over 48 weeks of ritlecitinib treatment • while salt ≤20 responses were lower in patients with at/au compared to those without at/au, a substantial proportion of patients with at/au still reported moderate or great improvement in their aa while receiving ritlecitinib, suggesting that many patients experienced meaningful benefit without achieving salt ≤20 response copies of this e-poster obtained through qr, ar and/or text key codes are for personal use only and may not be reproduced without written permission of the authors https://scientificpubs.congressposter.com/ p/vqkur0904pp3n1v5 58% 52% 56% 49% 59% 44% 42% 38% 49% 34% 45% 36% 40% 42% 41% 42% 50% 22% 40% 30% 64% 23% 41% 35% 71% 64% 61% 63% 73% 50% 100 week: 24 48 ritlecitinib 200/50 mg qd ritlecitinib 200/30 mg qd ritlecitinib 50 mg qd ritlecitinib 30 mg qd placebo → ritlecitinib 200/50 mg qd placebo → ritlecitinib 50 mg qd all aa at/au at au non-at/non-au 90 80 70 60 50 40 30 20 10 0 p ro po rt io n of p ar tic ip an ts w ith p g i-c r es po ns e (% ; 9 5% c i) 100 week: 24 48 ritlecitinib 200/50 mg qd ritlecitinib 200/30 mg qd ritlecitinib 50 mg qd ritlecitinib 30 mg qd placebo → ritlecitinib 200/50 mg qd placebo → ritlecitinib 50 mg qd all aa at/au at au non-at/non-au 90 80 70 60 50 40 30 20 10 0 p ro po rt io n of p ar tic ip an ts w ith s a lt s co re ≤ 20 (% ; 9 5% c i) 40% 43% 31% 34% 34% 19% 22% 25% 31% 16% 13% 14% 20% 27% 22% 19% 13%11% 12% 12% 6% 20% 20% 41% 54% 53% 45% 55% 22% 42% presented at winter clinical derm 2023, january 13–18, 2023 (encore of previous presentation at the european society of medical oncology [esmo] 2022, september 8–13, rabinowits g et al.). reused with permission. background • cscc is one of the most commonly diagnosed cancers worldwide, but epidemiologic information of the condition is very limited. • patient survival rates after early diagnosis of cscc are good, but morbidity and mortality rates in patients with advanced cscc not amenable to curative surgery or curative radiotherapy remain high, leaving a significant unmet need.1 • cemiplimab is a high-affinity, highly potent, fully human, immunoglobulin g4 monoclonal antibody to the programmed cell death (pd)-1 receptor, derived using velocimmune technology.2 • cemiplimab (cemiplimab-rwlc in the usa) is approved by the european medicines agency and the us food and drug administration for the treatment of adult patients with locally advanced or metastatic cscc who are not candidates for curative surgery or curative radiation; adult patients with locally advanced or metastatic basal cell carcinoma (bcc) previously treated with (us prescribing information [uspi])3/progressed on (summary of product characteristics [smpc])4 a hedgehog pathway inhibitor, or for whom a hedgehog pathway inhibitor is not appropriate (uspi)3/intolerant (smpc),4 and for first-line treatment of patients with locally advanced or metastatic non-small cell lung cancer who are not candidates for surgery or definitive chemoradiation and whose tumors have a tumor proportion score of ≥50% and with no egfr, alk, or ros1 aberrations.3,4 • limited data exist on the clinical characteristics, management, disease progression, and survivorship of patients with advanced cscc in real-world clinical practice. • here, we describe the demographics, effectiveness, and safety of an initial cohort of patients with advanced cscc treated with cemiplimab in real-world clinical practice and enrolled in the case study (nct03836105). cemiplimab-rwlc survivorship and epidemiology (case): a prospective study of the safety and efficacy of cemiplimab in patients with advanced cutaneous squamous cell carcinoma (cscc) in a real-world setting guilherme rabinowits,1 jade homsi,2 soo j park,3 nikhil khushalani,4 timothy panella,5 david m ellison,6 rhonda w gentry,7 suraj s venna,8 john strasswimmer,9 richard zuniga,10 sunandana chandra,11 emily s ruiz,12 michael r migden,13 sherrif f ibrahim,14 nikita mehta,15 timothy inocencio,16 xuanyao he,16 haixin r zhang,16 kathryn gillis,16 jean-francois pouliot16 1department of hematology and oncology, miami cancer institute/baptist health south florida, miami, fl, usa; 2university of texas southwestern medical center, dallas, tx, usa; 3division of hematology and oncology, university of california san diego, san diego, ca, usa; 4moffitt cancer center, tampa, fl, usa; 5university of tennessee medical center, knoxville, tn, usa; 6charleston oncology, charleston, sc, usa; 7carti cancer center, little rock, ar, usa; 8inova schar cancer institute melanoma center, fairfax, va, usa; 9college of medicine (dermatology) and college of sciences (biochemistry), florida atlantic university, boca raton, fl, usa; 10new york cancer and blood specialists, port jefferson, ny, usa; 11division of hematology and oncology, northwestern university feinberg school of medicine, chicago, il, usa; 12brigham and women’s hospital, boston, ma, usa; 13university of texas md anderson cancer center, houston, tx, usa; 14rochester dermatologic surgery, pc, victor, ny, usa; 15sanofi, cambridge, ma, usa; 16regeneron pharmaceuticals, inc., tarrytown, ny, usa results baseline demographics and disease characteristics • as of february 9, 2022, 198 patients were enrolled in the case study cscc cohort, 37 (18.7%) of whom were immunocompromised/immunosuppressed (ic/is). • of the total enrolled patient population,196 patients (including 36 who were ic/is) received at least one dose of cemiplimab (full analysis set). • demographics and safety data presented here are from the full analysis set; response assessment data is shown for patients who enrolled prior to starting cycle 3 of cemiplimab treatment. • median age was 76.0 years (range: 33.0–98.0), 75.5% of patients were male, and 90.3% were white (table 1). • ic/is patients were investigator reported and identified as having one or more of the following diagnoses in medical history: – inflammatory bowel diseases – leukemia – lupus – lymphoma – multiple myeloma – multiple sclerosis – rheumatoid arthritis – polycythemia vera – myeloproliferative disorder – chronic obstructive pulmonary disease with prednisone – undergone allogenic bone marrow or solid organ transplantation conclusions • observational studies such as case enroll a broader, real-world patient population that is not limited by stricter eligibility criteria. • the safety, tolerability, and effectiveness of cemiplimab in this initial cohort of patients with advanced cscc was generally consistent with that observed in clinical trials (nct02383212, nct02760498), considering real-world practice setting and a broader patient population. • in this initial cohort of patients who were identified as ic/is, the safety, tolerability, and effectiveness of cemiplimab was consistent with the overall patient population. • further follow-up and future analyses will provide additional outcomes measures and understanding of cemiplimab in the real-world setting (and during the covid-19 pandemic), in patients with advanced cscc and the subset of those who are ic/is. references 1. de jong e et al. j eur acad derm venereol. 2021;36(suppl. 1):6–10. 2. burova e et al. mol cancer ther. 2017;16:861–870. 3. regeneron pharmaceuticals, inc. libtayo® [cemiplimab-rwlc] injection full us prescribing information. available from: https://www. accessdata.fda.gov/drugsatfda_docs/label/2021/761097s007lbl.pdf [accessed jul 9, 2022]. 4. european medicines agency. libtayo® epar. available from: https://www.ema.europa.eu/en/medicines/human/epar/libtayo [accessed jul 25, 2022]. acknowledgments the authors thank the patients, their families, all other investigators, and all investigational site members involved in this study. the study was funded by regeneron pharmaceuticals, inc., and sanofi. medical writing support and typesetting was provided by jenna lee, msc, of prime, knutsford, uk, funded by regeneron pharmaceuticals, inc., and sanofi. disclosures guilherme rabinowits reports consulting/advisory roles for emd serono, pfizer, sanofi, regeneron pharmaceuticals, inc., and merck and castle; and stock/other ownership interests from syros pharmaceuticals and regeneron pharmaceuticals, inc. figure 1. study schema cscc, cutaneous squamous cell carcinoma; dcr, disease control rate; irae, immune-related adverse event; irr, infusion-related reaction; orr, objective response rate; tsar, treatment-related serious adverse reaction. patients with advanced cscc who are not candidates for surgery/radiation and who recently initiated cemiplimab treatment n=250–350 study endpoints • effectiveness: orr and dcr • safety: iraes, irrs, and tsars follow-up for 3 years off study at 3 years data collected at naturally occurring visits (every ~3 months) table 1. baseline demographics and tumor characteristics characteristic total (n=196) age, median (range), years 76.0 (33–98) male, n (%) 148 (75.5) white, n (%) 177 (90.3) ecog performance status, n (%) 0 43 (21.9) 1 89 (45.4) 2 18 (9.2) 3 2 (1.0) missing 44 (22.4) metastatic cscc, n (%) 72 (36.7) locally advanced cscc, n (%) 124 (63.3) current skin lesion locations, n (%) head and neck 136 (69.4) thorax and abdomen 18 (9.2) upper and lower extremities 54 (27.6) not known 9 (4.6) missing 3 (1.5) patients with prior radiation therapy, n (%) 84 (42.9) patients with prior surgery, n (%) 147 (75.0) patients with prior systemic therapy, n (%) 89 (45.4) multidisciplinary input, n (%) 85 (43.4) cscc, cutaneous squamous cell carcinoma; ecog, eastern cooperative oncology group. figure 2. duration of treatment exposure n u m b e r o f p a ti e n ts (n = 1 9 6 ) weeks ≥0 ≥3 ≥6 ≥12 ≥18 ≥24 ≥30 ≥36 ≥42 ≥48 196 (100%) 183 (93.4%) 174 (88.8%) 138 (70.4%) 120 (61.2%) 97 (49.5%) 81 (41.3%) 68 (34.7%) 57 (29.1%) 48 (24.5%) 250 200 150 100 50 0 table 3. safety data n (%) total (n=196) ic/is (n=36) any treatment-related sar 9 (4.6) 1 (2.8) led to discontinuation 5 (2.6) 0 led to death 1 (0.5) 0 colitis 2 (1.0) 0 adrenal insufficiency 1 (0.5) 0 autoimmune hepatitis 1 (0.5) 0 encephalitis 1 (0.5) 0 pneumonia 1 (0.5) 0 urosepsis 1 (0.5) 0 hyperglycemia 1 (0.5) 0 acute kidney injury 1 (0.5) 1 (2.8) pneumonitis 1 (0.5) 0 any treatment-related irae 49 (25.0) 7 (19.4) any infusion-related reaction 1 (0.5) 0 ic/is, immunocompromised/immunosuppressed; irae, immune-related adverse event; sar, serious adverse reaction. table 2. tumor response to cemiplimab patients who enrolled prior to cycle 3 (n=174) orr, % (95% ci) 37.4 (30.2–45.0) best overall response, n (%) complete response 17 (9.8) partial response 48 (27.6) stable disease 30 (17.2) progressive disease 13 (7.5) mixed response 4 (2.3) unable to evaluate 3 (1.7) not applicable 7 (4.0) dcr, % (95% ci) 54.6 (46.9–62.1) most mixed responses were evaluated by physician visual assessment and were not included in the calculation of orr or dcr. ci, confidence interval; dcr, disease control rate; orr, objective response rate. table 4. treatment discontinuation total (n=196) treatment ongoing, n (%) 85 (43.4) treatment discontinued, n (%) 111 (56.6) primary reason for treatment discontinuation, n (%)† adverse event 13 (11.7) complete response 6 (5.4) death 4 (3.6) disease progression 17 (15.3) lost to follow-up 1 (0.9) non-compliance 2 (1.8) other 16 (14.4) patient initiated cscc-related drug treatment 3 (2.7) patient initiated cscc-related surgery 3 (2.7) patient withdrawal 19 (17.1) physician decision 27 (24.3) primary reason for follow-up discontinuation, n (%)‡ completed 1 (1.6) death 29 (46.8) disease progression 4 (6.5) lost to follow-up 3 (4.8) patient withdrawal 18 (29.0) physician decision 3 (4.8) other 4 (6.5) †percentages are calculated from the number of patients who discontinued treatment (n=111). ‡percentages are calculated from the number of patients who discontinued from follow-up (n=62). cscc, cutaneous squamous cell carcinoma. methods • case is a prospective, non-interventional, multi-center, real-world, longitudinal study evaluating effectiveness, safety, qol, and survivorship in patients with advanced cscc treated with cemiplimab (figure 1). • the median duration of cemiplimab exposure was 23.3 weeks (interquartile range: 9.1–47.1) (figure 2). tumor response • efficacy was evaluated in patients who were enrolled prior to starting cycle 3 of cemiplimab treatment (n=174). – twenty-two patients were not included in the analysis, as informed consent and study enrollment were on or after the third dose of cemiplimab. • the orr as assessed and reported by the investigator for these patients was 37.4% (95% confidence interval [ci]: 30.2–45.0%; table 2). – seventeen (9.8%) patients had a complete response, and 48 (27.6%) patients had a partial response. • the orr for the ic/is population of patients who were enrolled prior to starting cycle 3 (n=28) was 42.9% (95% ci: 24.5–62.8%). • the dcr per investigator assessment was 54.6% (95% ci: 46.9–62.1%; table 2). safety data • safety was evaluated in all patients included in the study (n=196). • nine (4.6%) patients experienced a treatment-related serious adverse event (table 3). • forty-nine (25.0%) patients experienced a treatment-related irae, with the most common being hypothyroidism in 15 (7.7%) patients (table 3). • there was one event of death attributed to a treatment-related serious adverse event of pneumonitis (table 3). • thirteen (11.7%) patients discontinued due to an adverse event (table 4). • in general, cemiplimab was well-tolerated in ic/is patients: – one (2.8%) patient experienced a treatment-related serious adverse event of acute kidney injury (table 3). – seven (19.4%) patients experienced a treatment-related irae (table 3), including: – increased alanine aminotransferase – increased aspartate aminotransferase – pruritus – hypothyroidism – increased blood creatinine – decreased lymphocyte count – maculo-papular rash – acute kidney injury – fatigue limitations • not all patients were enrolled and followed within the study from the time of treatment, and there is inherent bias associated with observational studies versus a prospective interventional study. objectives • the objectives of the case study are to, in patients with advanced cscc or bcc in real-world clinical settings who received cemiplimab 350 mg administered intravenously (iv) every 3 weeks (q3w): – describe effectiveness based on objective response rate (orr) and disease control rate (dcr). – evaluate the safety of cemiplimab based on incidence of treatment-related immune-related adverse events (iraes), infusion-related reactions, and treatment-related serious adverse reactions. – investigate long-term effectiveness and quality of life (qol). • adult patients (aged ≥18 years) who had recently started or planned to start treatment of cscc or bcc with commercially available cemiplimab 350 mg iv q3w per the approved indication and routine standard of care at one of 43 us academic and community centers were eligible to be enrolled. • patients were excluded if they were receiving cemiplimab for indications other than cscc or advanced bcc, or if they had any condition that might interfere with participation in the study, restrict compliance with the treatment plan, or prevent completion of qol assessments. • tumors were assessed by computed tomography or magnetic resonance imaging, and response assessments were performed according to response evaluation criteria in solid tumours version 1.1. • the data cut-off was february 9, 2022. scan the qr code for co-author disclosures powerpoint presentation • of the 784 participants in the study, 280 were categorized as fitzpatrick skin type iv-vi and 64 patients were “black or african american”. the patient populations included in this subgroup analysis are presented in table 1. the number of participants who self-identified as “black or african american” was limited and the distribution was not balanced between the treatment groups; therefore, the results from this subgroup are not presented in the graphs. results valerie callender1, susan taylor2, fran cook-bolden3 1howard university college of medicine and callender dermatology & cosmetic center, glenn dale, md; 2department of dermatology, perelman school of medicine, university of pennsylvania, philadelphia, pa; 3mount sinai beth israel hospital, new york, new york calcipotriene (cal) and betamethasone dipropionate (bdp) cream demonstrates high efficacy and convenience in skin of color patients with plaque psoriasis • investigating the safety and efficacy of psoriasis therapies in diverse populations is important, given the potential for pharmacogenomic differences that may influence treatment outcomes. skin type, racial/ethnic, genetic and socioeconomic factors, are potential considerations when making treatment choices. • cal/bdp (cal 0.005%/bdp 0.064% w/w) is an effective medication for psoriasis and is now available in an aqueous cream made possible by pad™ technology1. here we describe the efficacy and convenience of cal/bdp cream in skin of color patients with plaque psoriasis. introduction • writing support was provided by anja snel-prentø, medlink. • the trial was funded by mc2 therapeutics. acknowledgements conclusions • this post hoc subgroup analysis shows that skin of color patients treated with cal/bdp cream have similar efficacy to the total trial population. • patient convenience and satisfaction for cal/bdp cream were scored similarly or higher in patients with skin of color than in the total trial population and compared to cal/bdp ts. • a limitation of the study is the number of african american patients is too small for statistical or descriptive comparison. methods • patients with mild to moderate plaque psoriasis were enrolled in a phase 3, randomized, multicenter, investigator-blind, parallel-group trial (nct03308799) comparing cal/bdp cream to cal/bdp topical suspension (ts) and cream vehicle.2 • patients were instructed to apply the trial medication topically to affected areas of the body once daily for up to 8 weeks. • physician global assessment (pga) treatment success (2-grade improvement and clear or almost clear) was the primary endpoint. • in this post-hoc subgroup analysis, we describe the efficacy and convenience of cal/bdp cream in skin of color patients (fitzpatrick skin type classification iv-vi and “black or african american”) compared to the total study population. • statistical analyses were based on a modified intent-to-treat (mitt) population (including all patients with at least one assessment of pga after starting treatment). figure 1. (a) type iv-vi group achieved more pga success after 8 weeks of treatment with cal/bdp cream than cal/bdp ts group or cream vehicle group (b) change from baseline in mpasi after 8 weeks of treatment with cal/bdp cream was 61.8% in the type iv-vi group similar to the total population pga, physician global assessment. mpasi, modified pasi. ptcs, psoriasis treatment convenience scale. bdp, betamethasone dipropionate; cal, calcipotriene; ts, topical suspension. mitt, modified intent-to-treat population including all patients with at least one pga assessment after starting treatment. figure 2. pga improvement of at least 1 grade and pga 0 (clear) or 1 (almost clear) showed similar trends with pga success 1 stein gold et al. j drugs dermatol. 2021 apr 1;20(4):420-425. doi: 10.36849/jdd.2021.5653. 2 feldman sr, præstegaard m, andreasen ah, selmer j, holm-larsen t. validation of the self-reported psoriasis treatment convenience scale (ptcs). dermatol ther (heidelb). 2021 dec;11(6):2077-2088. references table 2. psoriasis treatment convenience scale (ptcs)2 was significantly higher in cal/bdp cream than cal/bdp ts in the total population and the fitzpatrick type iv-vi groups. a) b) a) b) pga treatment success (2-grade improvement to clear or almost clear) % mpasi improvement from baseline pga improvement (at least 1 grade) pga satisfaction (clear or almost clear) 38.7 37.4 25.3 20.7 5 0.3 0 5 10 15 20 25 30 35 40 45 total population fitzpatrick type iv-vi % p g a s u c c e s cal/bdp cream cal/bdp ts cream vehicle 62.9 61.8 52 47.7 23.7 24.1 0 10 20 30 40 50 60 70 total population fitzpatrick type iv-vi m pa s i % r e d u c t io n cal/bdp cream cal/bdp ts vehicle 83.3 83.7 68.4 62.5 37.5 31.6 0 10 20 30 40 50 60 70 80 90 total population fitzpatrick type iv-vi % p g a i m p r o v e m e n t cal/bdp cream cal/bdp ts vehicle 48.7 46.7 30.9 27.7 9.5 5.7 0 10 20 30 40 50 60 total population fitzpatrick type iv-vi % p g a s a t is fa c t io n cal/bdp cream cal/bdp ts vehicle patient populations in subgroup analysis cal/bdp cream cal/bdp ts cream vehicle total total population (mitt) 338 (43.1%) 334 (42.6%) 112 (14.3%) 784 total population, safety set 342 (43.1%) 337 (42.4%) 115 (14.5%) 794 fitzpatrick skin type ivvi (mitt) 129 (16.5%) 114 (14.5%) 37 (4.7%) 280 (35.7%) fitzpatrick skin type ivvi, safety set 131 (16.5%) 116 (14.6%) 39 (4.9%) 286 (36.0%) black or african american (mitt) 34 (4.3%) 20 (2.6%) 10 (1.3%) 64 (8.2%) table 1 cal/bdp cream cal/ bdp ts cream vehicle total population: subjects with any teae, n (%) 90 (26.3) 76 (22.6) 32 (27.8) fitzpatrick skin type iv-vi: subjects with any teae, n (%) 36 (27.5) 28 (24.1) 6 (15.4) total population: subjects with any treatment-related teae, n (%) 12 (3.5) 11 (3.3) 5 (4.3) fitzpatrick skin type iv-vi: subjects with any treatment-related teae, n (%) 4 (3.1) 4 (3.4) 0 (0.0) table 3. skin of color patients demonstrated similar ae profile to the total population p=0.0002 p=0.0042 p<0.0001 p=0.003 p<0.0001 p<0.0001 p=0.0042 p=0.0002 question total population fitzpatrick iv-vi black or african american cream ts cream ts cream ts 1 how easy was the treatment to apply to the skin? 9.4 9.1 9.5 9.2 9.7 9.1 2 how greasy was the treatment when applying it to the skin? 7.5 6.0 7.9 5.9 7.8 5.4 3 how moisturized did your skin feel after applying the treatment? 8.1 7.7 8.2 7.6 8.9 8.1 4 how greasy did your skin feel after applying the treatment? 7.5 6.1 7.6 5.8 8.1 5.7 5 how much did treating your skin disrupt your daily routine? 9.0 8.7 8.9 8.7 9.0 8.6 total score (mitt, locf) 41.5 37.5 (p<0.0001) 41.8 36.9 (p<0.0001) 43.5 36.9 6 overall, how satisfied were you with the medical treatment 8.9 8.0 9.0 7.7 9.2 8.6 • “black or african american” patients scored higher in most of the individual scores than the total population, but the results should be interpreted cautiously due to the limited population size (see table 1). skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 187 compelling comments letter to the editor: commentary on “stigmatizing attitudes toward persons with psoriasis among laypersons and medical students” anisha guda bs1, john browning md2 1ut health san antonio long school of medicine, san antonio, tx 2adjunct associate professor, pediatrics and dermatology, ut health san antonio, san antonio, tx to the editor: we read with great interest the article by pearl et al in which the prevalence and predictors of stigmatizing attitudes among medical students and laypersons was determined.1 they found that laypersons view psoriasis as contagious and not a serious disease while medical students had less stigmatizing attitudes. they call for educational campaigns and advertisements that could mitigate the negative opinions of laypersons towards viewing psoriatic lesions while also minimizing stereotypes and myths.1 to further investigate the potential utility of educational campaigns, we searched for psoriasis social awareness events that had been organized in the past. we found that the national psoriasis foundation (npf) created the first “national psoriasis awareness month” in october 1997.2 they distributed messages about psoriasis in newspapers, the radio, and tv. the primary focus of their messages was that “psoriasis is not contagious”, “it is a serious public health problem and not a joking matter”, “psoriasis is a chronic skin disorder that can be quite severe for some people, even disabling”, and “it is important for people with psoriasis to know about npf”.2 the organizers found the campaign helpful in reaching people in certain localities and asked the public for new ideas. one of the kids participating in an npf contest created a poster called “psoriasis and me” depicting psoriatic patients in an animated form while making it clear that psoriasis is not contagious. 15,000 posters were distributed to various national organizations, physician offices, and on the tv series “er”.2 they were also able to recruit a spokesperson joe diffie who talked about his friend who had psoriasis and how it can greatly impact a person’s life. the psoriasis awareness month was eventually moved to august because there are more topics for themes including how the sun can help psoriasis. from then on, many more social awareness campaigns sprouted. the “show more of you” campaign organized by celgene showcased photographs of famous people living with psoriasis to raise awareness about psoriasis and empower them to live their life courageously.3 on the world psoriasis day organized by the international federation of psoriasis associations, brochures and flyers are distributed, awareness raising walks are organized, lectures are held, etc for the general population. the “are you serious” campaign organized by janssen biotech skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 188 had the comedian jon lovitz share his story about the day to day impact of psoriasis on his life. additionally, local psoriasis support groups throughout the country organize awareness events for the public. although there is a history of public awareness campaigns for psoriasis, there still seems to be a gap in the layperson’s understanding according to this study. perhaps, there needs to be more frequent social campaigns occurring in specific localities with more stigmatizing attitudes. if we can get more psoriasis patients to talk about their disease, this could also help reduce the stigma and gaps in knowledge. communicating with the npf, dermatologists, and pharmaceutical companies regarding the data from pearl et al is key in order to create targeted interventions for the community. conflict of interest disclosures: none funding: none corresponding author: anisha guda, bs 7458 louis pasteur drive san antonio, tx 78229 phone: 210-567-7000 email: gudav@livemail.uthscsa.edu references: 1. pearl rl, wan mt, takeshita j, and gelfand jm. stigmatizing attitudes toward persons with psoriasis among laypersons and medical students. jaad. 2019;80(6): 1556-1563. 2. bieler s. the forgotten history of psoriasis action month. national psoriasis foundation. https://www.psoriasis.org/advance/forgottenhistory-psoriasis-action-month. accessed 18 aug 2019. 3. shining a light on psoriatic disease. celgene. https://www.celgene.com/shining-light-psoriaticdisease/. accessed 18 aug 2019. mailto:gudav@livemail.uthscsa.edu https://www.psoriasis.org/advance/forgotten-history-psoriasis-action-month https://www.psoriasis.org/advance/forgotten-history-psoriasis-action-month https://www.celgene.com/shining-light-psoriatic-disease/ https://www.celgene.com/shining-light-psoriatic-disease/ slide 1  fas population included 406 subjects: 400 mg qd (n=101), 400 mg bid (n=102), 600 mg bid (n=101) and placebo (n=102). at week 24 , pasi-75 was achieved by 44.3%, 47.2% and 39.7% patients in ppc-06 600 mg bid, 400 mg bid and 400 mg qd groups, respectively, compared to 20% in the placebo group (p=0.004, 0.002 and 0.004 for the ppc-06 600 mg bid, 400 mg bid and 400 mg qd groups, respectively) (fig.1).  additionally, 44.4%, 41.4% and 35.7% of patients in the ppc-06 600 mg bid and 400 mg bid and 400 mg qd groups, respectively, achieved an iga score of 0/1 at week 24, compared to 22% of patients in the placebo group (p=0.010, 0.021 and 0.044 for the ppc-06 600 mg bid, 400 mg bid and 400 mg qd groups, respectively (fig.1).  multiple imputation was done for the missing efficacy data. diarrhea was the most common teae, reported in 7%, 18%, 23% and 5% of patients in the ppc-06 400 mg qd, 400 mg bid, 600 mg bid, and placebo groups, respectively. most cases being mild to moderate in severity. nausea, abdominal pain were reported in < 10% and flushing in 1-2% of ppc-06 population.  two subjects developed ctcae grade 3 lymphopenia with ppc-06, but recovered uneventfully on discontinuation of study drug. no new/unexpected adverse events were reported compared to what is known for dmf drugs. ppc-06 demonstrated significant efficacy compared to placebo over 24 weeks of treatment for three dose strengths. ppc-06 (tepilamide fumarate), a novel fumaric acid ester, is efficacious in treating plaque psoriasis: results from a phase 2b randomized controlled trial mark lebwohl, md1, leon kircik, md1,2, kristian reich, md3, sagar munjal, md, ms4, srinivas shenoy, md4, ulrich mrowietz md5 1mount sinai school of medicine, new york, ny; 2skin sciences, pllc, louisville, ky , 3university medical center hamburg-eppendorf, and skinflammation® center hamburg, germany, 4dr. reddy’s laboratories inc., princeton, nj, 5university medical center schleswigholstein, campus kiel, kiel, germany introduction  dimethyl fumarate (dmf) is approved in europe for the treatment of moderate to severe plaque psoriasis. monomethyl fumarate (mmf) is the active moiety.  ppc-06 is a novel extended release mmf donor being developed for treatment of moderate to severe plaque psoriasis. conclusions  ppc-06 may have potential to serve as an important therapeutic option for psoriasis patients in us as there are few oral treatments currently available. methods figure 1. co-primary outcomes at week 24  this phase 2b randomized, double blind, placebo-controlled, dose, regimen finding efficacy and safety study was conducted at 76 us sites.  enrolled patients had chronic plaque psoriasis, pasi (psoriasis area and severity index) ≥12, iga score (investigator’s global assessment) ≥3, and bsa (body surface area) ≥10%. 426 subjects were randomized in a 1:1:1:1 ratio into 4 dose arms: 400 mg qd, 400 mg bid, 600 mg bid, and placebo.  the co-primary end points at week 24 were pasi-75 (≥75% reduction from baseline pasi) and an iga score of ‘clear’/‘almost clear’ (i.e., 0/1). financial support: this study was funded and sponsored by the dr. reddy’s laboratories group of companies, princeton, nj, 08540, usa. drl publication # 885 results *statistical significance reported with placebo 0 10 20 30 40 50 60 70 80 90 100 pasi 75 iga (0/1) co-primary outcomes ppc-06 600mg bid, n=101 ppc-06 400mg bid, n=102 ppc-06 400mg qd, n=101 placebo, n=102 % s u b je c ts a c h ie v in g c o -p ri m a ry e n d p o in ts 44.4 * 47.2 39.7 20 44.3 41.4 35.7 22 * * * * * skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 300 short communications imiquimod-induced cutaneous lupus-like reaction: a potential histologic pitfall highlighting the importance of clinicopathologic correlation brian j simmons, md1, m shane chapman, md mba1, konstantinos linos, md2 1dartmouth-hitchcock medical center, section of dermatology, department of surgery, lebanon, nh 2dartmouth-hitchcock medical center, department of pathology, lebanon, nh although controversial, the use of imiquimod for the treatment of primary melanoma in-situ (mis) and residual mis after surgical excisions has become more common. this is especially true in patients with multiple medical comorbidities, treatment of cosmetically sensitive areas and when surgical intervention would lead to significant functional impairment.1 recognizing imiquimod-induced lupus-like reactions on histology is important and necessitates good clinicopathologic correlation given the potential ramifications of unnecessary laboratory workup and the need for systemic medications can be avoided. we report a case of lupus erythematous-like reaction in a patient being treated with imiquimod for residual mis of the face. an 84-year-old woman with a history of multiple skin cancers and dementia was found to have an invasive melanoma of the right nasal side wall with a breslow depth of 2.3mm. the patient underwent wide local excision with 2cm margins, sentinel lymph node biopsy negative and repair with a full thickness graft. the final clinical staging of melanoma was iia. however, margins were positive for mis. the patient was subsequently treated with topical 0.1% tretinoin daily for two weeks followed by imiquimod 5% cream 5 days a week for 12 weeks. thereafter, the patient developed a pink erythematous patch with overlying scale (figure 1). a scouting biopsy for residual mis at the edge of the graft at 12 weeks showed a lichenoid interface dermatitis with features resembling a mixed connective tissue disease (figure 2a & 2b) without residual mis, which resolved after completion of topical imiquimod. figure 1. faint pink erythematous patch with overlying scale after 2-week pretreatment with tretinoin 0.1% cream and 12-week field treatment with imiquimod 5% cream. skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 301 figure 2. (a) vacuolar interface dermatitis with lichenoid infiltrate (10x, hematoxylin and eosin). (b) scattered vacuolar interface with necrotic keratinocytes involving the dermoepidermal junction (20x, hematoxylin and eosin) imiquimod is a toll-like receptor 7 agonist approved for superficial basal cell carcinoma, actinic keratosis and external genital warts. common cutaneous reactions expected from treatment include erythema, pain, and erosions. in some instances, patients can have flu-like symptoms of fatigue and fever most pronounced when treating mucosal surfaces. on histologic examination, our patient’s imiquimod therapy induced a lupus-like interface reaction with adnexal vacuolar change, periadnexal lymphocytic infiltrates and colloid bodies that mimics cutaneous lupus.2 however, cutaneous lupus demonstrates dermal mucin deposition and increased thickness of the basement membrane, which distinguishes the two diagnoses on histologic examination. overall, imiquimod is thought to induce lupus erythematous-like microscopic findings via local upregulation of interferon alpha and/or direct pro-apoptotic activity via b-cell lymphoma 2(bcl-2) with subsequent activation of caspases.2 to date, there are 3 cases in the literature addressing this phenomenon in patients aged 75 to 91 years old for the treatment of actinic keratosis and lentigo maligna.2,3 however, with better long term efficacy data the use of imiquimod for the treatment of residual mis will continue to increase making the potential prevalence of a lupus-erythematous like reaction more common. hence, this case highlights the importance of clinicopathologic correlation and good communication between the dermatologist and dermatopathologist to arrive at the correct diagnosis. conflict of interest disclosures: none funding: none corresponding author: m. shane chapman one medical center dr. lebanon, nh 03756 phone: (603) 650-3156 fax: (603) 650-3174 email: brian.j.simmons@hitchcock.org references: 1. park aj, paul j, chapman ms, samie fh. long-term outcomes of melanoma in situ treated with topical 5% imiquimod cream: a retrospective review. dermatol surg. 2017;43(8):1017-1022. 2. barr kl, konia th, fung ma. lupus erythematosus-like imiquimod reaction: a diagnostic pitfall. j cutan pathol. 2011;38(4):346-350. 3. chan mp, zimarowski mj. lupus erythematosus-like reaction in imiquimodtreated skin: a report of 2 cases. am j dermatopathol. 2011;33(5):523-527. mailto:brian.j.simmons@hitchcock.org results patient demographics • a total of 600 patients ≥12 years old enrolled in the extension study; 311 and 289 were originally randomized to treatment with clascoterone and vehicle, respectively, in the phase 3 studies – the safety population included 598 patients treated with clascoterone (original randomization: 311 clascoterone, 287 vehicle) – the pp population included 319 patients, of whom 119 (37.3%) were on-study for a total of 12 months ○ during the phase 3 studies, 167 and 152 pp patients received clascoterone and vehicle, respectively ○ in the extension study, 124 pp patients also treated truncal acne, including 67 and 57 who received clascoterone and vehicle, respectively, during the phase 3 studies – the majority of patients were female and white; mean ± standard deviation age in the itt and pp populations was 19.3 ± 6.2 and 19.8 ± 6.6 years, respectively (table 1) table 1. patient demographics, subgroup ≥12 years old original treatment assignment clascoterone vehicle overall characteristic itt n = 311 pp n = 167 itt n = 289 pp n = 152 itt n = 600 pp n = 319 sex male 118 (37.9) 70 (41.9) 109 (37.7) 55 (36.2) 227 (37.8) 125 (39.2) female 193 (62.1) 97 (58.1) 180 (62.3) 97 (63.8) 373 (62.2) 194 (60.8) race caucasian 279 (89.7) 157 (94.0) 257 (88.9) 134 (88.2) 536 (89.3) 291 (91.2) asian 5 (1.6) 2 (1.2) 8 (2.8) 5 (3.3) 13 (2.2) 7 (2.2) black or african american 16 (5.1) 5 (3.0) 16 (5.5) 9 (5.9) 32 (5.3) 14 (4.4) other 11 (3.5) 3 (1.8) 8 (2.8) 4 (2.6) 19 (3.2) 7 (2.2) ethnicity hispanic or latino 26 (8.4) 9 (5.4) 15 (5.2) 7 (4.6) 41 (6.8) 16 (5.0) not hispanic or latino 285 (91.6) 158 (94.6) 274 (94.8) 145 (95.4) 559 (93.2) 303 (95.0) age, years mean 19.3 19.7 19.3 19.9 19.3 19.8 median 17.0 18 17.0 18.0 17.0 18.0 standard deviation 5.77 6.13 6.68 7.04 6.22 6.57 range 12–50 12–50 12–50 12–50 12–50 12–50 patients are summarized overall and according to the original treatment they received in the phase 3 pivotal studies. data shown as n (%) unless otherwise specified. itt, intention-to-treat; pp, per-protocol. safety • overall, 108/598 (18.1%) patients in the safety population experienced a total of 187 teaes, with similar frequencies in patients previously treated with clascoterone compared with vehicle in the phase 3 studies (table 2) – the majority of teaes reported were mild or moderate in severity, and most were not considered related to clascoterone treatment – the most frequent teaes by percentage of patients affected were nasopharyngitis (2.8%) and upper respiratory tract infection (1.8%; table 3) table 2. summary of teaes in patients ≥12 years old original treatment assignment category clascoterone vehicle overall n = 311 n = 287 n = 598 subjects with any teae 56 (18.0) 52 (18.1) 108 (18.1) mild 35 (11.3) 36 (12.5) 71 (11.9) moderate 27 (8.7) 23 (8.0) 50 (8.4) severe 4 (1.3) 3 (1.0) 7 (1.2) any test article–related teae 11 (3.5) 2 (0.7) 13 (2.2) any teae leading to discontinuation 9 (2.9) 0 9 (1.5) any serious teae 3 (1.0) 3 (1.0) 6 (1.0) any test article–related serious teae 0 0 0 any serious teae leading to discontinuation 1 (0.3) 0 1 (0.2) any teae leading to death 0 0 0 number of teaes, n 102 85 187 related to test article 16 2 18 not related to test article 86 83 169 mild 55 53 108 moderate 40 29 69 severe 7 3 10 patients are summarized overall and according to the original treatment they received in the phase 3 pivotal studies. safety population. data shown as n (%) unless otherwise specified. teae, treatment-emergent adverse event. long-term safety and efficacy of 1% clascoterone cream in patients ≥12 years old with acne vulgaris lawrence f eichenfield1, adelaide a hebert2, linda stein gold3, martina cartwright4, luigi moro5, jenny han6, nicholas squittieri7, alessandro mazzetti5 1university of california san diego school of medicine, la jolla, ca, usa; rady children’s hospital san diego, san diego, ca, usa; 2uthealth mcgovern medical school, houston, tx, usa; 3henry ford medical center, detroit, mi, usa; 4cassiopea inc., san diego, ca, usa; 5cassiopea s.p.a., lainate, italy; 6pharmapace inc., san diego, ca, usa; 7sun pharmaceutical industries, inc., princeton, nj, usa introduction • clascoterone cream 1% is a topical androgen receptor inhibitor approved for the treatment of acne vulgaris in patients aged ≥12 years old1 • clascoterone efficacy and safety were evaluated in two identical, vehicle-controlled, phase 3 studies (cb-03-01/25 and cb-03-01/26) in patients aged ≥9 years old with moderate-to-severe facial acne vulgaris – twice-daily treatment with clascoterone cream 1% for 12 weeks resulted in significantly higher treatment success rates and greater reduction in lesion counts compared with vehicle cream treatment2 – clascoterone was well tolerated, with a safety profile similar to that of vehicle • patients from the phase 3 studies could enter an optional long-term, open-label extension study; the safety results in patients ≥9 years old are published3 objective • to evaluate the long-term safety and efficacy of twice-daily 1% clascoterone cream in the subgroup of patients aged ≥12 years old who entered the long-term extension study methods study design and patients • a multicenter, open-label, long-term extension study (cb-03-01/27) enrolled patients who completed 1 of the 12-week phase 3 clinical trials (cb-03-01/25 and cb-03-01/26) • male or nonpregnant female patients who completed 1 of the 12-week phase 3 pivotal clinical trials (cb-03-01/25 and cb-03-01/26) and enrolled within 3 days of the final pivotal trial visit were eligible – patients with any skin pathology or condition that could interfere with the study or who planned to use other topical or systemic antiacne preparations or undergo procedures on the face (or trunk, if applicable) were excluded – this analysis includes only patients aged ≥12 years old who entered the long-term extension study treatment administered • patients applied 1% clascoterone cream twice daily to the entire face and, if designated by the investigator and desired by the patient, to truncal acne, for 9 additional months of treatment – total time applying clascoterone cream, including the phase 3 studies, could be up to 12 months for patients originally randomized to clascoterone treatment – clascoterone treatment could be discontinued if the investigator’s global assessment (iga) score was 0 or 1 (clear/almost clear) and reinstated if/when acne worsened assessments • safety was evaluated from frequencies of treatment-emergent adverse events (teaes), serious adverse events, and local skin reactions (lsrs), including telangiectasia, skin atrophy, striae rubrae, erythema, edema, scaling/dryness, stinging/ burning, and pruritus – summarized in patients ≥12 years old who received at least one application of clascoterone (safety population) • efficacy was evaluated from the iga severity score for each treatment area, as applicable – assessed at every in-clinic study visit (baseline and months 1, 3, 6, and 9) using a 5-point iga scale (0, clear; 4, severe) – summarized in patients ≥12 years old who completed the study without significant protocol violations (per-protocol [pp] population) statistical analysis • for demographic, efficacy, and safety data, continuous variables were described by descriptive statistics, and categorical data by frequency counts and percentage of patients within each category – patient demographics are reported in the subgroup of patients ≥12 years old in the intention-to-treat (itt) population • missing data were not imputed table 3. most frequent teaes in patients ≥12 years old original treatment assignment category clascoterone vehicle overall n = 311 n = 287 n = 598 most frequent teaes events, n patients events, n patients events, n patients application site acne 4 4 (1.3) 0 0 4 4 (0.7) nasopharyngitis 7 6 (1.9) 14 11 (3.8) 21 17 (2.8) respiratory tract infection, viral 1 1 (0.3) 4 4 (1.4) 5 5 (0.8) sinusitis 3 3 (1.0) 2 2 (0.7) 5 5 (0.8) upper respiratory tract infection 9 8 (2.6) 3 3 (1.0) 12 11 (1.8) patients are summarized overall and according to the original treatment they received in the phase 3 pivotal studies. safety population. data shown as n (%) unless otherwise specified. teae, treatment-emergent adverse event. • the frequency of lsrs on the face and trunk was low; frequencies were similar in patients previously treated with clascoterone compared with vehicle in the phase 3 studies – the most common new or worsening lsrs in patients previously treated with clascoterone/vehicle were scaling/dryness (face, 10.0%/7.3%; trunk, 3.5%/4.5%) and erythema (face, 8.0%/7.7%; trunk, 6.1%/7.3%; table 4) • no deaths were reported during the study table 4. new or worsening lsrs on the face and trunk in patients ≥12 years old original treatment assignment symptom clascoterone n = 311 vehicle n = 287 face trunk face trunk edema 5 (1.6) 1 (0.3) 5 (1.7) 5 (1.7) erythema 25 (8.0) 19 (6.1) 22 (7.7) 21 (7.3) pruritus 13 (4.2) 5 (1.6) 16 (5.6) 4 (1.4) scaling/dryness 31 (10.0) 11 (3.5) 21 (7.3) 13 (4.5) skin atrophy 3 (1.0) 1 (0.3) 4 (1.4) 4 (1.4) stinging/burning 11 (3.5) 1 (0.3) 8 (2.8) 2 (0.7) striae rubrae 1 (0.3) 2 (0.6) 2 (0.7) 1 (0.3) telangiectasia 3 (1.0) 1 (0.3) 4 (1.4) 1 (0.3) patients are summarized according to the original treatment they received in the phase 3 pivotal studies. safety population. data shown as n (%) unless otherwise specified. lsr, local skin reaction. efficacy • among patients who completed the study without major protocol violations, the proportion with clear or almost-clear facial acne (iga score 0/1) increased over time during treatment with 1% clascoterone cream, with almost half of patients (48.9%) overall having a facial iga score of 0/1 at the end of the study (9 months; figure 1) – similar proportions of patients who originally received 1% clascoterone cream or vehicle in the phase 3 studies were clear or almost clear at the end of the study figure 1. percentage of patients ≥12 years old with facial iga 0/1 by visit baseline 1 month 3 months 6 months 9 months 0 20 40 60 80 100 % p at ie nt s clascoterone-to-clascoterone (n = 167) vehicle-to-clascoterone (n = 152) total (n = 319) 18.0 8.6 13.5 10.2 11.8 11.0 13.8 13.8 13.8 32.3 25.0 28.8 50.3 47.4 48.9 patients are summarized overall and according to the original treatment they received in the phase 3 pivotal studies. per-protocol population. data shown as % unless otherwise specified. iga, investigator’s global assessment. • the overall proportion of pp patients with clear or almost-clear truncal acne increased over time during 1% clascoterone cream treatment (figure 2) – at the end of the study, the proportion of patients with a truncal iga score of 0/1 was higher among those originally assigned to treatment with 1% clascoterone cream vs vehicle (61.2% vs 42.1%, respectively) figure 2. percentage of patients ≥12 years old with truncal iga 0/1 by visit baseline 1 month 3 months 6 months 9 months 0 20 40 60 80 100 3.0 5.3 4.0 23.9 14.0 19.4 34.3 26.3 30.6 44.8 45.6 45.2 61.2 42.1 52.4 % p at ie nt s clascoterone-to-clascoterone (n = 67) vehicle-to-clascoterone (n = 57) total (n = 124) patients are summarized overall and according to the original treatment they received in the phase 3 pivotal studies. per-protocol population. data shown as % unless otherwise specified. iga, investigator’s global assessment. • consistent with iga results at each study visit, the overall proportions of pp patients who were clear or almost clear on the face increased with time on 1% clascoterone treatment, with the greatest proportion of patients who were clear or almost clear observed in patients applying clascoterone for 12 months (67/119 [56.3%]) conclusion • clascoterone cream 1% applied twice daily was well tolerated, and frequencies of teaes and lsrs were low throughout the study – most reported teaes were mild in severity, and there was no accumulation of adverse events observed over time – no patient deaths were reported • among patients who completed the study without major protocol violations, the proportion achieving clear or almost-clear skin on the face and trunk increased with duration of 1% clascoterone cream treatment and was highest for patients on-study for 12 months of treatment acknowledgments the studies were funded by cassiopea s.p.a. medical writing and editorial support were provided by dana lengel, phd, of alphabiocom, llc, and funded by sun pharma. disclosures lfe, aah, and lsg were study investigators. lfe, aah, and lsg were also compensated advisors to cassiopea. aah is an employee of the mcgovern medical school of the university of texas health science center at houston, which received compensation from cassiopea s.p.a. for study participation; she also received an honorarium for serving on the cassiopea advisory board; all research grant funds were paid to her institution. lfe is an employee of the university of california san diego, which received compensation from cassiopea s.p.a. for study participation; he has also served as an investigator, advisor, or consultant for almirall, dermata, galderma laboratories, and ortho dermatologics. lsg is an employee of the henry ford health system in detroit, michigan, which received compensation from cassiopea s.p.a. for study participation; she also received personal fees for advisory, speaking, consulting, research, and/or other services with almirall, foamix, galderma laboratories, novartis, sol-gel, and sun pharma. mc is employed as the vice president of medical affairs at novan inc.; was employed as the senior director of medical affairs at cassiopea, inc. at the time of the study; received personal fees as a consultant from cassiopea s.p.a.; and receives personal fees as an adjunct faculty member from the university of arizona. lm is an employee of cassiopea s.p.a. and holds stock options in the company. jh is an employee of pharmapace inc. ns is an employee of sun pharmaceutical industries, inc. am is employed as the chief medical officer for cassiopea s.p.a. and holds stock options in the company; is a board member of cassiopea s.p.a.; and served as the chief medical officer of cosmo pharmaceuticals. references 1. winlevi® (clascoterone cream 1%) [package insert]. sun pharmaceutical industries, inc.; 2020. 2. hebert a, et al. jama dermatol. 2020;156(6):621–630. 3. eichenfield l, et al. j am acad dermatol. 2020;83(2):477–485. powerpoint presentation efgartigimod: clinical development of a novel fcrn antagonist in the treatment of autoimmune diseases olga ostrovskaya,1 magdalena sips,1 peter ulrichts,1 lance trainor,1 peter verheesen,1 ivaylo stoykov1 1argenx, ghent, belgium • the neonatal fc receptor, fcrn, recycles immunoglobulin g (igg), extending its half-life and serum concentration1 • efgartigimod is a human igg1 fc fragment, a natural ligand of fcrn, engineered for increased affinity for fcrn2 • efgartigimod was designed to outcompete endogenous igg, preventing recycling and promoting lysosomal degradation of igg, without impacting its production2–5 o targeted reduction of all igg subtypes o no impact on igm or iga o no reduction in albumin levels o no increase in cholesterol 1. sesarman a, et al. cell mol life sci. 2010;67:2533–50. 2. ulrichts p, et al. j clin invest. 2018;128:4372–86. 3. vaccaro c, et al. nat biotech. 2005;23:1283–88. 4. newland ac, et al. am j hematol. 2020;95:178–87. 5. goebeler m, et al. br j dermatol. 2022;10:1111. 6. howard jf jr, et al. lancet neurol. 2021;20:526–36. 7. argenx, inc. (march 22, 2022). topline results: adapt-sc bridging study in gmg. 8. argenx, inc. (may 5, 2022). topline results: advance study in itp. 9. schmidt e, et al. lancet. 2019;394:882. 10. amagai m, et al. j am acad dermatol. 1999;40:167–70. 11. kridin k, et al. front med (laussane). 2018;5:220. references oo, ms, pu, lt, pv, is: employees of argenx. clinical trials mentioned above are funded by argenx. disclosures & acknowledgments pemphigus and bullous pemphigoid: igg-mediated autoimmune diseases9–11 • pv and pf belong to a heterogeneous group of autoimmune blistering diseases and are clinically characterized by mucosal erosions (pv) and cutaneous blisters (pv and pf) • pv is characterized by the presence of pathogenic igg autoantibodies targeting desmoglein 3 (dsg-3), and 50% of the cases, also against desmoglein 1 (dsg-1) • pf is attributed to the presence of igg autoantibodies solely directed against dsg-1 • pemphigus is potentially life-threatening, primarily due to secondary infections • bullous pemphigoid (bp) is the most prevalent autoimmune blistering disease; it is characterized by subepidermal blisters and mediated by igg autoantibodies directed against bp-230 and bp-180 antigens iv, intravenous; sc, subcutaneous. efgartigimod is co-formulated with hyaluronidase ph20 for convenient sc administration in <2 min. the investigational study drug, efgartigimod, has not been approved for use in pv/pf or bp by any regulatory agency as efficacy and safety have not been established. presented at the 2023 winter clinical dermatology conference; january 13–18, 2023; kohala coast, hi. efgartigimod: engineered igg1 fc fragment1–5 program indication preclinical phase 1 phase 2 phase 3 efgartigimod generalized myasthenia gravis (sc) chronic inflammatory demyelinating polyneuropathy (sc) idiopathic inflammatory myopathy/myositis (sc) pemphigus vulgaris and foliaceus (sc) bullous pemphigoid (sc) primary immune thrombocytopenia (iv) primary immune thrombocytopenia (sc) membranous nephropathy lupus nephritis sjogren syndrome covid-19 mediated postural orthostatic tachycardia syndrome argx-117 multifocal motor neuropathy delayed graft function after kidney transplantation argx-119 neuromuscular indications argx-120 undisclosed argx-118 airway inflammation (non-autoimmune program) efgartigimod is approved for the treatment of gmg in patients positive for achr antibodies in the us, as an add-on to standard therapy in patients positive for achr antibodies in the emea, and in patients with and without achr antibodies with insufficient response to steroids or nonsteroid immunosuppressive therapies in japan efgartigimod is also being evaluated in phase 3 trials in chronic inflammatory demyelinating polyneuropathy, idiopathic inflammatory myositis, pemphigus (pv and pf), bp, and primary itp efgartigimod reduces total igg including pathogenic igg autoantibody levels4–7 • in a phase 2 study of participants with itp, treatment with efgartigimod iv 10 mg/kg induced a reduction in serum levels of total igg up to a mean change of 64% from baseline4 o in 70% of participants treated with efgartigimod iv 10 mg/kg, a reduction >40% in at least 1 type of platelet-associated autoantibody (gpiib/iiia, gpib/ix, gpia/iia) signal was observed at days 25/29 and/or day 784 • in a phase 2 study of participants with pv or pf, serum total igg levels decreased by a median of 62% with efgartigimod iv 10 mg/kg and by a median of 66% with efgartigimod iv 25 mg/kg5 o at the end of induction, serum levels of anti-dsg-1 and anti-dsg-3 igg reached a median 61% reduction from baseline for anti-dsg-1 and 49% for antidsg-3 antibodies5 • in a phase 3 study of participants with gmg positive for acetylcholine receptor (achr) antibodies, a mean maximum reduction of total igg by 61.3% was observed in participants treated with efgartigimod iv 10 mg/kg6 mean percentage change from baseline in serum levels of total igg in participants with gmg, primary itp, and healthy volunteers treated with efgartigimod iv.4,6 gmg, generalized myasthenia gravis; hv, healthy volunteer; igg, immunoglobulin g; itp, immune thrombocytopenia; iv, intravenous; se, standard error. -100 -90 -80 -70 -60 -50 -40 -30 -20 -10 0 10 0 1 2 3 4 5 6 7 8 9 10 11 12 total igg – hv vs patients patients with gmg (argx-113-1602) patients with itp (argx-113-1603) healthy volunteers (argx-113-1702) patients with gmg (argx-113-1704) m ea n (± se ) t ot al ig g c ha ng e fr om b as el in e (% ) neuromuscular hematology dermatology nephrology other image adapted from kang th, jung st. boosting therapeutic potency of antibodies by taming fc domain functions. exp mol med. 2019;51:1-9 and distributed under the terms of the creative commons cc-by license (https://creativecommons.org/licenses/by/4.0/). efgartigimod is clinically effective and well tolerated in phase 2 and 3 trials in igg-mediated disorders4–8 • consistent depletion of total igg levels of roughly 60% from baseline with efgartigimod intravenous (iv) treatment was observed across studies and populations • in an open-label, phase 2 trial with efgartigimod iv in participants with pemphigus (pemphigus vulgaris [pv] and pemphigus foliaceus [pf]), disease control was achieved in 90% of participants (median time: 17 days) • topline results of a phase 3, randomized, placebo-controlled study (advance iv) with efgartigimod iv in participants with primary immune thrombocytopenia (itp) have also reported efficacy and safety in this patient population the primary endpoint, platelet-related key secondary endpoints, and international working group response criteria were met; no new safety signals were observed • in a phase 3 trial in participants with generalized myasthenia gravis (gmg), 68% of participants responded to efgartigimod iv (mg-adl responders*) compared with 30% of those in the placebo group o in a study comparing efgartigimod administered intravenously or subcutaneously in participants with gmg, consistent clinical efficacy and safety were observed in both groups (mg-adl responders: 69.1% iv vs 69.1% subcutaneous [sc]; n=110) • efgartigimod treatment was generally well tolerated in phase 2 and 3 trials in participants with pemphigus (open-label study), primary itp, and gmg o most common adverse events in treatment and placebo groups across studies to date include headache, nausea, nasopharyngitis, diarrhea, abdominal pain, upper respiratory tract infection, and urinary tract infection *mg-adl responders = ≥2-point myasthenia gravis activities of daily living score improvement sustained for ≥4 weeks. week slide number 1 << /ascii85encodepages false /allowtransparency false /autopositionepsfiles true /autorotatepages /none /binding /left /calgrayprofile (dot gain 20%) /calrgbprofile (srgb iec61966-2.1) /calcmykprofile (u.s. web coated \050swop\051 v2) /srgbprofile (srgb iec61966-2.1) /cannotembedfontpolicy /warning /compatibilitylevel 1.3 /compressobjects /off /compresspages false /convertimagestoindexed true /passthroughjpegimages true /createjobticket false 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reported instances of skin atrophy, striae, telangiectasia, or folliculitis in the scalp psoriasis study – only application site dermatitis (n=3) was reported in the palmoplantar psoriasis study scalp psoriasis study6 • in a single-center, open-label pilot study, adult participants who had moderate-to-severe psoriasis with scalp involvement (n=21) applied hp/taz once daily for 8 weeks and were followed for 4 weeks posttreatment (week 12; n=20) • the primary endpoint was proportion of participants with an investigator’s global assessment (iga) score of 0 or 1 (clear or almost clear) at week 8 • other outcomes included 75%/90%/100% improvement in psoriasis scalp severity index (pssi 75/90/100, respectively) and scalp iga (siga) improvement results • in the palmoplantar study, mean pppga scores improved significantly with hp/taz treatment from baseline to week 24 (p=0.0165; figure 2)5 figure 2. improvements in palmoplantar physician global assessment from baseline to week 24 in patients receiving hp/taz. hp/taz, halobetasol propionate 0.01% and tazarotene 0.045%; locf, last observation carried forward.5 • at week 8 in the scalp psoriasis study6: – 10/21 patients (48%) achieved a score of iga 0 or 1 – 15/21 patients (>70%) achieved an siga score of 0 or 1, and 50% maintained these scores at week 12 (figure 3) – nearly one-third of patients (29%) had siga 0, and 20% maintained siga 0 at week 12 • significant improvements from baseline in pssi 75 rates were observed at weeks 4, 8, and 12 (p≤0.0005 for all) • rates of pssi 75/90/100 were maintained from week 8 to 12 (figure 4) – pssi 75: 67% of patients achieved pssi 75 at week 8, with 45% maintaining at week 12 – pssi 90: 38% of patients achieved pssi 90, with 30% maintaining at week 12 – pssi 100: 29% of patients achieved pssi 100, with 20% maintaining at week 12 objective • to review previously published results from openlabel studies of hp/taz in palmoplantar psoriasis and scalp psoriasis in the context of reduction of proinflammatory mediators such as tnf-α conclusion • the inhibition of tnf-α by hp/taz could potentially contribute to the effectiveness of hp/taz in psoriasis lesions involving difficult-totreat areas synopsis • tumor necrosis factor α (tnf-α) plays a key role in the pathogenesis of psoriasis and is a target of systemic therapies1 – systemic tnf-α inhibitors have been shown to be efficacious against difficult-to-treat areas of psoriasis2 • a recent study showed that fixed-combination halobetasol propionate 0.01%/tazarotene 0.045% lotion (hp/taz) substantially reduced tnf-α levels in psoriatic plaques at weeks 2 through 12 of treatment compared with levels in untreated plaques (figure 1)3 figure 1. tnf-α levels in plaques treated with hp/taz vs untreated plaques across 12 weeks.3 tnf-α, tumor necrosis factor alpha. • the additive effect of hp and taz on reduction of proinflammatory mediators such as tnf-α4 may improve outcomes in difficult-to-treat areas, such as the palms, soles of the feet, and scalp – the combined benefits of hp/taz could result from nonoverlapping immunogenetic mechanisms of hp and taz4 – additionally, taz may mitigate the risk of skin atrophy associated with prolonged topical corticosteroid use4 methods palmoplantar psoriasis study5 • in an investigator-initiated, open-label study, adult participants with moderate-to-severe palmoplantar psoriasis (n=17) were treated once daily with hp/taz for 24 weeks – psoriasis severity was assessed by the palmoplantar physician global assessment (pppga), with a score of 0 indicating “clear” and a score of 5 indicating “severe” – pppga was assessed at baseline and again at week 24 use of combination halobetasol propionate/tazarotene lotion in difficult-totreat psoriasis and tnf-α mechanism of action leon kircik,1 zoe draelos,2 linda stein gold,3 abby jacobson4 1icahn school of medicine at mount sinai, new york, ny; 2dermatology consulting services, pllc, high point, nc; 3henry ford health system, detroit, mi; 4ortho dermatologics (a division of bausch health us, llc), bridgewater, nj presented at winter clinical dermatology conference® • january 13-18, 2023 • kohala coast, hi sponsored by ortho dermatologics, a division of bausch health us, llc. 0 2 4 8 12 -2 0 2 4 8 6 10 12 week; 0 = bl t n fα, p g/ m l treated untreated control tnf-α 0 1 2 4 3 5 6 baseline (week 0) week 24/locf pa lm o pl an ta r ph ys ic ia n g lo ba l a ss es sm en t mean=2.82 mean=3.47 52 71 50 0 20 40 60 80 100 week 4 week 8 week 12 (posttreatment) pa ti en ts , % siga (absent or very mild) 67 45 38 3029 20 0 20 40 60 80 100 week 8 week 12 pa ti en ts ,% pssi 75 pssi 90 pssi 100 funding: this study was supported by ortho dermatologics. editorial assistance was provided under the direction of the authors by medthink scicom. previous presentation information: data in this poster have been published previously (ozyurekoglu and kircik. j drugs dermatol. 2021;20:1191-1194) and were presented at the 2022 american academy of dermatology annual meeting; march 25-29, 2022; boston, ma, and at the fall clinical dermatology conference; october 20-23, 2022; virtual and las vegas, nv. references: 1. chima and lebwohl. semin cutan med surg. 2018;37:134-142. 2. lanna et al. dermatol ther. 2020;33:e13374. 3. draelos et al. presented at: fcdc 42nd annual fall clinical dermatology conference; october 20-23, 2022; virtual and las vegas, nv. 4. lebwohl et al. dermatol ther (heidelb). 2021;11:1157-1174. 5. campbell et al. presented at: american academy of dermatology annual meeting; march 25-29, 2022; boston, ma. 6. ozyurekoglu and kircik. j drugs dermatol. 2021;20:1191-1194. author disclosures: lk has served as an investigator, speaker, advisory board member, or consultant for abbott laboratories; aclaris, inc; allergan, inc; amgen inc; anacor pharmaceuticals, inc; assos pharma; astellas pharma us, inc; asubio pharma co, ltd; berlex laboratories (bayer healthcare pharmaceuticals); biogen-idec, inc; biolife; biopelle; boehringer ingelheim; breckinridge pharma; celgene corporation; centocor, inc; colbar; collagenex; combinatrix; connetics corporation; coria; dermik laboratories; dermira, inc; dow pharmaceutical sciences, inc; dusa pharmaceuticals, inc; eli lilly & co; embil pharmaceutical co, ltd; eos; ferndale laboratories, inc; galderma laboratories, lp; genentech, inc; glaxosmithkline, plc; health point ltd; idera, inc; innocutis medical, llc; innovail; intendis, inc; johnson & johnson; laboratory skin care, inc; leo pharmaceuticals, inc; l’oreal sa; 3m; maruho co, ltd; medical international technologies; medicis pharmaceutical corp; merck & co, inc; merz; nano bio corporation; novartis pharmaceutical corporation; noven pharmaceuticals, inc; nucryst pharmaceuticals corporation; obagi medical products, inc; onset; orthoneutrogena; pediapharma, inc; promius pharma, llc; pharmaderm; pfizer, inc; puracap; qlt, inc; quatrix; quinnova; serono (merck-serono international sa); skinmedica, inc; stiefel laboratories, inc; sun pharmaceutical industries, ltd; taro; tolerrx, inc; triax; ucb, inc; valeant pharmaceuticals north america llc; warner-chilcott; xenoport, inc; and zage. zd received funding from ortho dermatologics to conduct the research detailed in the poster. lsg has served as an investigator/advisor and/or speaker for almirall, galderma, ortho derm, sun, novartis, sol gel, and vyne. aj is an employee of ortho dermatologics (a division of bausch health us, llc). presenting author: leon kircik; wedoderm@yahoo.com acknowledgements: medical writing support was provided by prescott medical communications group (chicago, il) with financial support from ortho dermatologics | presented at the fall clinical dermatology conference • october 17-20, 2019 • las vegas, nv synopsis ◾ tretinoin is a topical retinoid for the treatment of acne vulgaris, but current gel, foam, or cream formulations can cause irritation, limiting their use1 ◾ tretinoin 0.05% lotion (altreno® ortho dermatologics, bridgewater, nj) is a novel topical formulation—developed by utilizing polymeric emulsion technology2—that has demonstrated efficacy and safety for the treatment of moderate‑to‑severe acne3,4 objective ◾ to assess the compatibility of tretinoin 0.05% lotion with foundation makeup immediately and 6 hours after application, as well as skin texture after makeup application methods ◾ this was a single‑center, evaluator‑blinded, randomized, controlled study; eligible participants were females aged 18‑50 years who used facial foundation makeup ≥5 days per week ◾ participants were randomized to apply tretinoin 0.05% lotion to either the right or left side of the face before applying full‑face foundation makeup ◾ investigator‑assessed foundation coverage and cutaneous tolerability were evaluated immediately after tretinoin application and foundation application and again at 6 hours post‑foundation application • in this study, cerave® hydrating cleanser and cerave® moisturizing lotion (l’oreal, ny) were provided as needed for optimal moisturization/cleaning of the skin ◾ the participant‑assessed makeup appearance questionnaire and facial images were obtained at the same timepoints for analysis of skin texture roughness using antera 3d® imaging (miravex limited, dublin, ireland) results ◾ a total of 30 participants were enrolled in the study (intent‑to‑treat [itt] population) and 29 completed (per protocol population); 6 participants had fitzpatrick skin type v or vi (table 1) a randomized, observer‑blind, split‑face study to assess compatibility of facial foundation makeup with tretinoin 0.05% lotion and skin texture after application neal bhatia, md1; leon h. kircik md2,3,4; ava shamban, md5; varsha bhatt, phd6; radhakrishnan pillai, phd6; eric guenin, pharmd, phd, mph7 1therapeutics clinical research, san diego, california; 2indiana university school of medicine, indianapolis, in; 3physicians skin care, pllc, louisville, ky; 4icahn school of medicine at mount sinai, new york, ny; 5ava md santa monica, medical and cosmetic dermatology, santa monica, ca; 6bausch health americas, inc., petaluma, ca; 7ortho dermatologics, bridgewater, nj ◾ per participant ratings, even/full coverage and skin smoothness were significantly better on the treated side than on the untreated side immediately after foundation application (p=0.03 and p=0.01, respectively; figure 2a) • no significant differences in makeup appearance were found at hour 6 (figure 2a) • participants indicated overall satisfaction with the tretinoin‑treated side (figure 2b) ◾ no significant differences in skin texture roughness were observed in the facial images between the tretinoin‑treated and untreated sides after 6 hours compared with post‑foundation application, or immediately after foundation application and at hour 6 compared with post‑treatment application figure 2. participant‑assessed makeup appearance scores (pp population) a. makeup appearance items 4: strongly agree 3: agree somewhat 2: disagree somewhat 1: strongly disagree p a rt ic ip a n t r a ti n g , m e a n s co re ± s d my makeup foundation has a natural-looking appearance my makeup foundation appears to have an even full coverage my skin appears to be smooth with my makeup foundation applied with my makeup foundation, my skin tone appears to be even treated: post-makeup application untreated: post-makeup application treated: at hour six untreated: at hour six b. participant satisfaction items treated: at hour six 4: strongly agree 3: agree somewhat 2: disagree somewhat 1: strongly disagree i feel satis�ed with applying this treatment under my foundation makeup it was easy to apply my foundation makeup after thetreatment i feel con�dent wearing foundation makeup after applying the treatment i feel i can add the treatment to my everyday routine before applying foundation makeup treated: post-makeup application p a rt ic ip a n t r a ti n g , m e a n s co re ± s d *p<0.05 vs untreated post-makeup application. treated=tretinoin 0.05% lotion. pp, per protocol; sd, standard deviation. ◾ consistent with phase 3 studies,3 most cutaneous tolerability outcomes had a rating of “none” from all 30 participants; no outcome was rated as “severe” by any participant • some participants experienced mild erythema, dryness, and itching; 1 participant had moderate itching on the treated side at hour 6 (table 2) table 2. number of participants with mild or moderate ratings in cutaneous tolerabilitya post‑foundation, n at hour 6, n mild moderate mild moderate erythema treated 4 0 4 0 untreated 4 0 4 0 dryness treated 3 0 1 0 untreated 4 0 2 0 burning treated 0 0 0 1 untreated 0 0 0 0 itching treated 0 0 1 0 untreated 0 0 0 0 a all 30 intent-to-treat participants rated the following outcomes as “none” for both sides at both timepoints: edema, peeling, and stinging. conclusions ◾ tretinoin 0.05% lotion was comparable to no treatment in most evaluations, but appeared beneficial with participant‑assessed foundation coverage and skin smoothness immediately after foundation application ◾ tretinoin lotion was also compatible for up to 6 hours post‑foundation application and was well‑tolerated references 1. zaenglein al, et al. j am acad dermatol. 2016;74(5):945-973. 2. kircik lh, et al. j drugs dermatol. 2019;18(4):s148-154. 3. tyring sk, et al. j drugs dermatol. 2018;17(10):1084-1091. 4. harper jc, et al. j dermatolog treat. 2019:1-8. author disclosures dr. bhatia has received honoraria from ferndale laboratories, inc., promius pharma, llc, novartis, allergan, biofrontera ag, intraderm pharmaceuticals, almirall, sun pharmaceutical industries, la roche-posay, mayne pharma group, ortho dermatologics, pierre fabre dermo-cosmétique us, isdin, galderma laboratories, skinfix, inc., and grants/research funding from aclaris therapeutics, inc., asana biosciences, llc, crown laboratories, inc., leo pharma us, dusa pharmaceuticals, inc., menlo therapeutics, par pharmaceutical, pfizer inc., perrigo company, realm therapeutics, sienna biopharmaceuticals, sol-gel technologies, soligenix, inc., strata skin sciences, vidac pharma, brickell biotech, inc., dermira, glenmark generics inc., sanofi/regeneron, actavis, biopharmx, foamix, cutanea life sciences, mc2 therapeutics, ucb, abbvie, atacama therapeutics, naked biome inc., kiniksa pharmaceuticals, ltd., bms, dr. reddy, and vypome (pending). dr. leon kircik has acted as an investigator, advisor, speaker, and consultant for ortho dermatologics. dr. ava shamban has received grants/ research support and/or consulting from galderma, merz, endo, brickell, b10, revance, teoxane, and allergan. drs. varsha bhatt and radhakrishnan pillai are employees of bausch health americas. dr. eric guenin is an employee of ortho dermatologics. table 1. participant demographics (itt population) participants (n=30) age, mean (sd), y 35.2 (8.3) female, n (%) 30 (100) race, n (%) white 23 (76.7) black 6 (20.0) multiracial 1 (3.3) ethnicity, n (%) not hispanic or latino 20 (66.7) hispanic or latino 10 (33.3) fitzpatrick skin type, n (%) i 2 (6.7) ii 7 (23.3) iii 8 (26.7) iv 7 (23.3) v 5 (16.7) vi 1 (3.3) itt, intent-to-treat; sd, standard deviation. ◾ there were no significant differences between the tretinoin‑treated and untreated sides for any outcome for clinical grading of foundation coverage (figure 1) • on the untreated side, there was a small but statistically significant worsening in percent coverage figure 1. investigator‑assessed clinical grading of foundation coverage scores (pp population) 0 1 2 3 4 5 6 7 8 9 none (best possible condition) m ild m o d e ra te s e ve re c lin ic a l g ra d in g , m e a n s co re ± s d percent coverage blotchiness overall coverage skin tone (color) evenness visual smoothness treated: post-makeup application untreated: post-makeup application treated: at hour six untreated: at hour six *p<0.05 vs untreated post-makeup application. treated=tretinoin 0.05% lotion. pp, per protocol; sd, standard deviation. powerpoint presentation real-world baseline characteristics and early patient-reported outcomes in adult patients with moderate-tosevere atopic dermatitis treated with tralokinumab peter lio1, yestle kim2, sanjeev balu2, adriana guana2, dawn bates3, demauri s. mackie3, halley costantino3, amanda lopez4, jennifer soung5 1. northwestern university feinberg school of medicine and medical dermatology associates of chicago, usa; 2. leo pharma, madison, nj; 3. cerner enviza, kansas city, mo; 4. patient living with atopic dermatitis; 5. harbor-ucla medical center table 1. baseline demographic and disease characteristics conclusions • this interim real-world analysis of the ongoing study describes the baseline characteristics of patients who were prescribed tralokinumab in the us • after 4 weeks of tralokinumab use, patients saw improvements in itch, sleep, quality of life, and treatment satisfaction; additionally, over a third of patients experienced clinically important improvements in these outcomes • from baseline to week 4, there was a reduction in patients using topical corticosteroids (86.5% to 39.6%) and topical calcineurin inhibitors (33.3% to 17.7%) • there were improvements seen in both the dupilumab-experienced and the dupilumabnaïve groups from baseline to week 4, although lower rates were seen in the dupilumabexperienced group as this group may be a more difficult-to-treat population • the interim data show promising early improvements, but longer-term data are needed as tralokinumab clinical trials have shown that improvements continue and maintain over a longer period of time objective the objective of this interim analysis from this ongoing prospective study is to report the baseline characteristics and evaluate the early (4-week) real-world impact on patient-reported outcomes (pros) of patients treated with tralokinumab for moderate-to-severe atopic dermatitis materials and methods study design and patient cohort • patients were asked to participate in this study through the adbrytm advocatetm program (hub) within 1 week of their tralokinumab initiation • full-length web-based surveys will be completed at baseline, 4 weeks, 24 weeks, 36 weeks, and 52 weeks, with shorter pulse surveys conducted in between (figure 1) • this interim analysis include patients who were evaluated via web-based surveys at baseline and after 4 weeks • the demographic and disease characteristics are presented in this poster endpoints and analyses • pro endpoints included the patient-oriented scoring atopic dermatitis (po-scorad) index, dermatology life quality index (dlqi), average weekly itch numeric rating scale (nrs), worst weekly itch nrs, ad-related weekly sleep nrs, and treatment satisfaction questionnaire for medication (tsqm-9) • pro results were reported as the change in score or percentage change in score from baseline to week 4 • dlqi and nrs items are also presented as the proportion achieving a 4-point improvement from baseline to week 4 (wave 1) • results are presented descriptively for the total population and by use of dupilumab at any time (at the time of completion of the baseline survey) results demographics and disease characteristics • as of august 2022, 96 adult patients completed the baseline and week 4 surveys • patients were mainly female (59.4%) and white (82.3%) with a mean age of 44.4 (sd=15.0) years (table 1) • their mean age at ad diagnosis was 26.8 (sd=22.0) years and most patients were diagnosed 17.6 (sd=17.8) years ago (table 1) references 1. bieber t. n engl j med. 2008;358(14):1483-1494; 2. weidinger s, novak n. lancet. 2016;387(10023):1109-1122; 3. kiebert g et al. int j dermatol. 2002;41(3):151-158; 4. simpson el, et al. ann allergy asthma immunol. 2022;129:592-604 disclosures pl has received research grants/funding from abbvie, aobiome, the national eczema association, and regeneron/sanofi genzyme. he is on speaker’s bureaus for regeneron/sanofi genzyme, leo pharma, galderma, incyte, eli lilly, l'oreal, leo pharma, pfizer, and regeneron/sanofi genzyme. he reports payments for serving on consulting or advisory boards for abbvie, almirall, amyris, aobiome, arbonne, aslan pharmaceuticals, bodewell, bristol myers squibb, burt's bees, concerto biosciences (stock options), dermavant, eli lilly, exeltis, galderma, intraderm, johnson & johnson, kimberly-clark, kiniksa, leo pharma, l'oreal, menlo therapeutics, merck, micreos (stock options), my-or diagnostics, pierre-fabre, pfizer, realm therapeutics, regeneron/sanofi genzyme, pfizer, leo pharma, ucb, unilever, and verrica. in addition, dr. lio has a patent pending for a theraplex product with royalties paid and is a board member and scientific advisory committee member of the national eczema association. yk, sb, ag are employees of leo pharma, inc. db, dm, hc are employees of cerner enviza, an oracle company; have served in a consulting or advisory role for leo pharma; and have received research funding from leo pharma. js received honoraria and research grants from celgene, amgen, eli lilly, abbvie, pfizer, ortho dermatologics, national psoriasis foundation, leo pharma, novartis, regeneron, sanofi, ucb, janssen, kyowa kirin, dermavant, bms, arcutis, kobio labs, and castel biosciences. she is on speaker’s bureaus for celgene, amgen, eli lilly, abbvie, pfizer, ortho dermatologics, national psoriasis foundation, novartis, regeneron, sanofi, bms, and arcutis. dr. soung has been an investigator for eli lilly, pfizer, leo pharma, novartis, ucb, janssen, kyowa kirin, dermavant, arcutis, kobio labs, and castel biosciences. she reports payments for serving on consulting or advisory boards for eli lilly, leo pharma, novartis, dermavant, and bms. introduction • atopic dermatitis (ad) is characterized mainly by widespread skin lesions and itch, and is associated with a substantial disease burden and decreased quality of life1-3 • tralokinumab-ldrm (adbrytm) was approved in the us in december 2021 for the treatment of moderateto-severe ad in adult patients • currently, there is very little data on the real-world experience or outcomes associated with tralokinumab utilization • this study will provide insights into the impact of tralokinumab on adult patients in the real world (nonclinical trial) setting • goal of this study is to have at least 250 patients complete the study from baseline to 52 weeks summary of po-scorad and tsqm-9 • after 4 weeks of tralokinumab use, patients saw improvements in their po-scorad (13.6%, sd=62.6%) and average weekly itch (22.3%, sd=48.8%) scores (table 2) • patients also saw improvements in their mean tsqm-9 global satisfaction (6.0 points, sd=23.3), tsqm-9 convenience (9.8 points, sd=20.7), and tsqm-9 effectiveness (5.1 points, sd=18.3) scores (table 2) • improvements were seen in both ‘ever taken dupilumab’ and ‘never taken dupilumab’ groups in poscord and tsqm-9 outcomes (table 2) abbreviations %, percentage; ad, atopic dermatitis; dlqi, dermatology life quality index; max, maximum; min, minimum; n, number of patients; nrs, numeric rating scale; poscorad, patient-oriented scoring atopic dermatitis; pro, patient-reported outcomes; tsqm-9, treatment satisfaction questionnaire for medication. *age at diagnosis is an approximation based on year of diagnosis and approximate year of birth (based on age at the time of study) summary of concomitant medication use • patients were generally treatment experienced at baseline, with 86.5% previously treated with topical corticosteroids (prescription or non-prescription), 54.2% previously treated with dupilumab, 33.3% previously treated with topical calcineurin inhibitor, and 53.1% previously treated with a prescription oral corticosteroid (figure 2a) • topical treatments were generally taken as concomitant medications at week 4, with 39.6% of patients using topical corticosteroids (prescription or non-prescription), 17.7% using a topical calcineurin inhibitor (prescription), and 14.6% using ruxolitinib (figure 2b) • patients who reported having ever taken dupilumab at baseline report a greater use of prior and concomitant medications compared to those who had never taken dupilumab at baseline disease characteristics itch nrs, sleep nrs, concomitant medicationsdemographics dosing frequency po-scorad, dlqi, tsqm-9 0 4 8 12 242 16 20week 36 5228 32 40 44 48 baseline (tralokinumab initiation) total patients on tralokinumab (n=96) ever taken dupilumab (n=52) never taken dupilumab (n=44) current age (years) mean (sd) 44.40 (15.01) 41.54 (14.89) 47.77 (14.60) median (min; max) 44.5 (18; 71) 38.5 (18; 71) 51.0 (20; 69) sex at birth n (%) female 57 (59.4) 34 (65.4) 23 (52.3) male 38 (39.6) 17 (32.7) 21 (47.7) decline to answer 1 (1.0) 1 (1.9) 0 (0.0) ethnicity n (%) hispanic or latino 6 (6.3) 4 (7.7) 2 (4.5) not hispanic or latino 87 (90.6) 46 (88.5) 41 (93.2) decline to answer 3 (3.1) 2 (3.8) 1 (2.3) race n (%) white 79 (82.3) 45 (86.5) 34 (77.3) asian or asian american 12 (12.5) 5 (9.6) 7 (15.9) black or african american 6 (6.3) 3 (5.8) 3 (6.8) other race or origin 3 (3.1) 3 (5.8) 0 (0.0) decline to answer 3 (3.1) 0 (0.0) 3 (6.8) diagnosed medical conditions n (%) allergies 54 (56.3) 30 (57.7) 24 (54.5) anxiety 37 (38.5) 23 (44.2) 14 (31.8) asthma 26 (27.1) 16 (30.8) 10 (22.7) depression 25 (26.0) 17 (32.7) 8 (18.2) history of conjunctivitis (pink eye) 7 (7.3) 5 (9.6) 2 (4.5) age at diagnosis of ad/eczema (years)* mean (sd) 26.76 (22.04) 19.38 (20.27) 35.48 (21.02) median (min; max) 23.5 (0; 69) 10.5 (0; 64) 38.5 (0; 69) duration of ad/eczema (years)* mean (sd) 17.64 (17.85) 22.15 (16.93) 12.30 (17.60) median (min; max) 12 (0; 68) 21 (0; 56) 3 (0; 68) 2.a. previously or at time of taking baseline survey 2.b. at week 4 (wave 1 survey) table 2. improvement in patient reported outcomes wave 1 (4-weeks post-initiation) from baseline (initiation) total patients on tralokinumab (n=96) ever taken dupilumab (n=52) never taken dupilumab (n=44) po-scorad n 96 52 44 mean score at baseline (sd) 46.01 (22.15) 45.67 (21.46) 46.41 (23.19) mean % improvement at week 4 (sd) 13.56 (62.56) 2.37 (74.64) 26.79 (41.33) median % improvement at week 4 (min; max) 22.08 (-443.90; 100.00) 21.79 (-443.90; 71.38) 26.80 (-78.31; 100.00) average weekly itch nrs (% improvement) n 92 49 43 mean score at baseline (sd) 5.53 (2.58) 5.35 (2.72) 5.75 (2.42) mean % improvement at week 4 (sd) 22.33 (48.78) 14.71 (50.88) 31.02 (45.30) median % improvement at week 4 (min; max) 25.00 (-200; 100.00) 25.00 (-200; 100.00) 25.00 (-66.67; 100.00) average weekly itch meaningful improvement meaningful improvement (3-points), n (%) 32 (33.3) 16 (30.8) 16 (36.4) worst weekly itch nrs n 96 52 44 mean score at baseline (sd) 6.66 (2.78) 6.56 (2.85) 6.77 (2.73) mean % improvement at week 4 (sd) 18.54 (59.50) 10.39 (63.42) 27.83 (53.93) median % improvement at week 4 (min; max) 22.22 (-300; 100) 22.22 (-300, 80) 22.22 (-150; 100) sleep interference nrs n 96 52 44 mean score at baseline (sd) 4.20 (3.43) 3.96 (3.43) 4.48 (3.44) mean % improvement at week 4 (sd) 21.03 (55.28) 12.31 (60.58) 31.80 (46.57) median % improvement at week 4 (min; max) 25 (-100; 100) 13.39 (-100; 100) 29.29 (-50; 100) dlqi n 96 52 44 mean score at baseline (sd) 10.50 (6.45) 9.58 (5.89) 11.59 (6.98) mean % improvement at week 4 (sd) 26.29 (52.42) 15.70 (59.14) 38.56 (40.67) median % improvement at week 4 (min; max) 33.33 (-250; 100) 25 (-250; 100) 42.48 (-100; 100) dlqi meaningful improvement meaningful improvement (4-points), n(%) 41 (42.7) 17 (32.7) 24 (54.5) tsqm-9: global satisfaction mean score improvement (sd) 5.95 (23.36) 4.40 (21.60) 7.79 (25.21) median score improvement (min; max) 3.57 (-50.00; 71.43) 0.00 (-50.00; 71.43) 7.14 (-50.00; 64.29) tsqm-9: convenience mean score improvement (sd) 9.78 (20.70) 10.04 (21.08) 9.47 (20.49) median score improvement (min; max) 8.33 (-55.56; 66.67) 5.56 (-55.56; 66.67) 11.11 (-33.33; 61.11) tsqm-9: effectiveness mean score improvement (sd) 5.09 (18.27) 2.78 (18.69) 7.83 (17.58) median score improvement (min; max) 5.56 (-44.44; 50.00) 0.00 (-44.44; 50.00) 11.11 (-38.89; 44.44) summary of dlqi and nrs • improvement on dlqi, average weekly itch nrs, and sleep interference nrs was seen in the total population; improvements were seen in both the ‘ever taken dupilumab’ and the ‘never taken dupilumab’ groups (table 2, figure 3) • the ‘ever taken dupilumab’ group improved at a lower rate compared to the ‘never taken dupilumab’ group, as this group may be a more difficult-to-treat population • the mean percentage improvement in dlqi and worst weekly itch nrs were 26.3% (sd=52.4%) and 18.5% (sd=59.5%) • clinically meaningful improvement was experienced by 33.3% of patients on the average weekly itch nrs and 42.7% of patients on the dlqi • the improvement in these outcomes is similar or was at a lower proportion than what was seen in the ecztra clinical trials at the same time point, although the differences in study designs and the small sample size of this study are not conducive for a comparison with the clinical trials4 figure 3. 3.a. dlqi 3.b. worst weekly itch nrs 3.c. sleep nrs figure 1. study data collection figure 2. top 3 medications taken for atopic dermatitis/eczema mean percentage improvement in score from baseline to week 4 39.60% 17.70% 14.60% 31.80% 15.90% 11.40% 46.20% 19.20% 17.30% 0.00% 5.00%10.00%15.00%20.00%25.00%30.00%35.00%40.00%45.00%50.00% topical corticosteroid topical calcineurin inhibitor ruxolitinib cream ever taken dupilumab (n=52) never taken dupilumab (n=44) all patients on tralokinumab (n=96) 0.00% 5.00% 10.00% 15.00% 20.00% 25.00% 30.00% 35.00% 40.00% 45.00% week 0 week 4 m e a n % i m p ro v e m e n t fr o m b a s e lin e all patients on tralokinumab (n=96) never taken dupilumab (n=44) ever taken dupilumab (n=52) 0.00% 5.00% 10.00% 15.00% 20.00% 25.00% 30.00% week 0 week 4m e a n % i m p ro v e m e n t fr o m b a s e lin e all patients on tralokinumab (n=96) never taken dupilumab (n=44) ever taken dupilumab (n=52) 0.00% 5.00% 10.00% 15.00% 20.00% 25.00% 30.00% 35.00% week 0 week 4 m e a n % i m p ro v e m e n t fr o m b a s e lin e all patients on tralokinumab (n=96) never taken dupilumab (n=44) ever taken dupilumab (n=52) 86.50% 33.30% 53.10% 86.40% 22.70% 43.20% 86.50% 42.30% 61.50% 0.00%10.00%20.00%30.00%40.00%50.00%60.00%70.00%80.00%90.00%100.00% topical corticosteroid topical calcineurin inhibitor oral corticosteroid ever taken dupilumab (n=52) never taken dupilumab (n=44) all patients on tralokinumab (n=96) slide 1: real-world baseline characteristics and early patient-reported outcomes in adult patients with moderate-to-severe atopic dermatitis treated with tralokinumab powerpoint presentation integration of the 40-gene expression profile (40-gep) for management and treatment of high-risk cutaneous squamous cell carcinoma (cscc): a real-world algorithm gaurav singh, md, mph, faad1, stanislav n. tolkachjov, md2,3, aaron s. farberg, md4 1gaurav singh md, milwaukee, wi; 2epiphany dermatology, dallas, tx; 3university of texas at southwestern, dallas, tx; 4baylor scott & white health system, dallas, tx background › the prognostic 40-gene expression profile (40-gep) test has established both analytical and improved clinical validity for risk stratification when compared to current staging systems. the test categorizes patients as low (class 1), moderate (class 2a), or high (class 2b) risk for regional or distant metastasis within 3 years of diagnosis.1-3 › clinical utility studies of the 40-gep test have demonstrated its appropriate use for the intended high-risk population, and its ability to direct personalized risk-aligned patient management while also increasing clinician confidence in treatment decisions. 4-8 gs is a consultant for castle biosciences inc. (cbi); asf is an advisor for cbi and regeneron; snt declares no relevant conflicts of interest. the authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed herein. cases presentations presented at winter clinical dermatology conferences: january 13-18, 2023, kohala coast, hawaii and february 17-20, 2023, miami, fl for more information: aaron.farberg@gmail.com conclusions disclosures clinical issue and objective for high-risk cscc patients, the limitations of risk-stratification tools, along with broad treatment guidelines, has led to disparities in clinical practice and management, creating a diversity of patient outcomes.8 the objective of this study is to provide guidance to clinicians regarding how to incorporate the results of the 40-gep test into common treatment modalities for their high-risk cscc patients. scan here for more info clinicopathologic risk factors case report 1 case report 2 case report 3 • 74-year-old male • 2.2 cm diameter, moderately differentiated • located on the left posterior scalp • >90 year-old male • 3.1cm diameter, moderately differentiated • located on left central lateral neck • 63-year-old male • >2cm diameter, invasion beyond subcutaneous fat • located on head region disease presentation and progression american joint committee on cancer (ajccv8) and brigham and women’s hospital (bwh) stage ajcc v8: t2 bwh: t2a ajcc v8: t2 bwh: t2a ajcc v8: t3 bwh: t2b rationale for 40-gep 2.2 cm diameter, multiple stages of mohs surgery, larger defect size (4.2 x 4.2cm) multiple stages of mohs surgery, larger defect size (4.4 x 4.1cm) multiple stages of mohs surgery, poor clinical margins, patient with a history of multiple csccs treatment approach pre-40-gep ct scan, rt, and follow-up every 1-month slnb, rt, and follow-up every 6 months imaging to evaluate for distant metastasis was considered 40-gep result class 1 (low risk) class 2a (moderate risk) class 2a (moderate risk) treatment approach post-40-gep forgo rt and ct scan; follow-up for monthly wound check and nodal exams every 6 months forgo slnb and radiation with follow-up scheduled for every 3 months surveillance of lymph nodes with ultrasound imaging every 6 months for two years and clinical follow-up every 3 months with lymph node exam outcomes one-year post-treatment, the wound healed with no evidence of recurrence or metastasis. 3 months post treatment, the wound has healed with no evidence of recurrence or metastasis 16 months post-treatment the wound healed with no evidence of disease presentation histological diagnosis post-procedurehistological diagnosis presentation mohs surgery mohs surgery mohs surgery figure 1. treatment algorithm for incorporation of 40-gep test results into treatment decisions for a high-risk cscc patient patient diagnosed with primary invasive cscc and one or more risk factors patient qualifies for 40-gep testing; clinician sends primary tumor ffpe for biologic metastatic risk prediction due to complexities in patient’s clinicopathologic risk factors, clinician decides further assessment is needed adjuvant radiation therapy nodal assessment class 1 class 2a class 2b no action if low tstage & negative palpation discuss and consider slnb and/or surveillance for high and very high risk every 6 mo for 2 yr every 3-6 mo for 1 yr every 2-3 mo for 1 yr **discuss mri, us and/or ct **consider mri, us and/or ct no action if extensive disease is not present treatment* no action if high risk and negative surgical margins consider for very high risk and high t-staged high risk recommend for very high risk and high tstaged high risk clinical follow up surveillance imaging *multidisciplinary board should be considered; **choice of imaging technique dependent on number and type of high-risk factors; us= ultrasonography; ct= computed tomography; ffpe=formalin-fixed paraffin-embedded surveillance suggested for high and very high risk references 1. wysong, et al jaad 2021 2. ibrahim, et al future oncol 2021 5. farberg, et al cmro 2020 6. litchman, et al cmro 2020 3. borman, et al diagn path 2022 4. teplitz, et al jdd 2019 7. au, et al dermatol ther 2022 8. blomberg, et al br j derm 2017 9. nccn v2.2022 methods › private practice mohs surgeons who have utilized 40-gep results for prognostication of high-risk scc patients merged their risk-aligned management approaches into a singular algorithm focused on how to incorporate 40-gep test results within the management guidelines proposed by the national comprehensive cancer network (nccn)9 (figure 1). › real-world cases were compiled by the authors to evaluate the following treatment modalities: surveillance imaging, sentinel lymph node biopsy (snlb), adjuvant radiation therapy (art), and clinical follow-up. mohs surgery presentation histological diagnosis post-procedure m a n a g e m e n t d e c is io n s w it h in n c c n g u id e li n e s post-procedure › for high-risk cscc patients, whose management is currently broad under existing guidelines, clinicians can identify risk-aligned treatment pathway improvements by use of the 40-gep within their existing clinical practices. › one such algorithm to incorporate the 40-gep is presented here as a mechanism to implement guideline recommendations for personalized management of patients based on their risk for poor outcomes. conclusions https://castlebiosciences.com/research-development/publications/ slide 1 tapinarof cream for the treatment of plaque psoriasis: efficacy and safety by baseline disease characteristics and skin type in a phase 2b randomized study mark lebwohl, md;1 james del rosso, do;2 chih-ho hong, md;3 anna m. tallman, pharmd;4 leon kircik, md1,5 1icahn school of medicine at mount sinai, new york, ny, usa; 2jdr dermatology research/thomas dermatology, las vegas, nv, usa; 3university of british columbia and probity medical research, surrey, bc, canada; 4dermavant sciences, inc., new york, ny, usa; 5skin sciences, pllc, louisville, ky, usa. introduction ■ psoriasis is a chronic, immune-mediated disease characterized by scaly, erythematous, and pruritic plaques that can be painful and disfiguring1 ■ although multiple options are available for the treatment of plaque psoriasis, there is a need for effective topical therapies that can be used without body surface area (bsa) restrictions or concerns for the duration of treatment ■ tapinarof cream is a therapeutic aryl hydrocarbon receptor modulating agent (tama) under investigation for the treatment of psoriasis (clinicaltrials.gov id: nct03956355) and atopic dermatitis ■ this previously conducted phase 2b dose-finding study (clinicaltrials.gov id: nct02564042) was designed to assess the efficacy and safety of tapinarof cream in subjects with plaque psoriasis2,3 ■ factors related to disease characteristics and skin type may influence clinical outcomes in psoriasis4,5 ■ this post-hoc analysis was conducted to explore whether the efficacy and safety of tapinarof cream varied across subgroups by baseline disease characteristics and skin type objective ■ to evaluate the efficacy and safety of tapinarof through post-hoc analysis from a phase 2b study in subjects with plaque psoriasis stratified by baseline disease characteristics, including % bsa affected, duration of psoriasis, and fitzpatrick skin type methods study design ■ in this multicenter (united states, canada, and japan), phase 2b, double-blind, vehiclecontrolled randomized study, adult subjects with psoriasis were randomized 1:1:1:1:1:1 to receive tapinarof cream 0.5% or 1% once (qd) or twice daily (bid) or vehicle qd or bid for 12 weeks and followed up for 4 more weeks (figure 1) figure 1. study design tapinarof 1% bid (n=38) tapinarof 1% qd (n=38) tapinarof 0.5% bid (n=38) tapinarof 0.5% qd (n=38) vehicle bid (n=37) vehicle qd (n=38) offtreatment adult subjects with stable plaque psoriasis for ≥6 months • aged 18–65 years • bsa ≥1%–≤15%* • pga ≥2 (n=227) r double-blind treatment (12 weeks) follow-up (4 weeks) *excluding scalp. bid, twice daily; bsa, body surface area; pga, physician global assessment; qd, once daily. study outcomes and statistical analysis ■ the primary endpoint was physician global assessment (pga) response rates at week 12, defined as the proportion of subjects with a pga score of clear or almost clear (0 or 1) and ≥2-grade improvement in pga score from baseline to week 122 ■ additional post-hoc efficacy analyses reported here include pga response rates at week 12, stratified by the following baseline disease characteristics and skin type: – baseline % bsa affected: 1 to <10% and ≥10% – baseline duration of psoriasis: 6 months to <5 years, 5 years to <10 years, and ≥10 years – fitzpatrick skin type: fitzpatrick skin type i and ii, fitzpatrick skin type iii and iv, and fitzpatrick skin type v and vi ■ incidence, frequency, and nature of adverse events (aes) and serious aes were collected from the start of study treatment until the end of study visit at week 16 results subject characteristics ■ a total of 227 subjects (of the 290 subjects originally screened) were randomized (intent-to-treat population) and of those randomized, 175 subjects (77%) completed the study, including the week 16 follow-up visit ■ mean demographic and baseline characteristics were comparable across treatment groups (table 1) ■ overall, 15% of subjects had a baseline pga category of 2 (mild), 80% had a pga category of 3 (moderate), and 5% had a pga category of 4 (severe) ■ baseline mean psoriasis area and severity index score was 8.8 (standard deviation [sd] 4.5) table 1. baseline subject demographics and characteristics tapinarof 1% cream tapinarof 0.5% cream vehicle bid (n=38) qd (n=38) bid (n=38) qd (n=38) bid (n=37) qd (n=38) mean age, years (sd) 45.9 (11.9) 48.5 (10.6) 49.6 (10.9) 48.7 (9.7) 46.7 (12.6) 46.4 (10.2) male sex, n (%) 26 (68) 26 (68) 24 (63) 25 (66) 23 (62) 29 (76) mean weight, kg (sd) 85.6 (22.5) 86.7 (22.6) 88.6 (27.4) 89.3 (23.1) 87.8 (28.3) 91.6 (21.6) pga, mean (sd) 2.9 (0.4) 2.7 (0.5) 3.0 (0.5) 2.9 (0.4) 3.0 (0.3) 2.8 (0.4) pasi, mean (sd) 10.6 (5.0) 8.5 (3.6) 8.2 (4.5) 7.9 (4.8) 9.0 (4.3) 8.7 (4.4) % bsa affected, mean (sd) 8.2 (4.5) 6.5 (3.3) 7.2 (4.5) 6.1 (4.3) 6.6 (3.6) 7.0 (4.6) pruritus score, mean (sd)* 5.6 (2.6) 4.4 (2.9) 6.2 (2.2) 4.5 (2.6) 5.5 (2.8) 4.9 (2.4) mean duration of psoriasis, years (sd) 15.7 (14.1) 16.6 (12.9) 17.9 (14.1) 16.6 (13.3) 18.1 (15.0) 16.0 (12.4) fitzpatrick skin type i, n (%) 2 (6) 3 (9) 1 (3) 2 (6) 1 (3) 1 (3) fitzpatrick skin type ii, n (%) 8 (24) 7 (20) 10 (31) 6 (19) 5 (17) 13 (39) fitzpatrick skin type iii, n (%) 17 (50) 14 (40) 6 (19) 13 (41) 11 (37) 11 (33) fitzpatrick skin type iv, n (%) 2 (6) 7 (20) 7 (22) 7 (22) 7 (23) 5 (15) fitzpatrick skin type v, n (%) 5 (15) 3 (9) 5 (16) 4 (13) 5 (17) 3 (9) fitzpatrick skin type vi, n (%) 0 1 (3) 3 (9) 0 1 (3) 0 baseline disease characteristics provided for the mitt population (n=196), which included subjects in the itt population minus the subjects from one site due to protocol violation. demographics (age, sex, and weight) provided for the safety population (n=227). *mean scores based on an nrs of 0 ‘absent’ to 10 ‘worst imaginable’; data provided for subjects with available results (n=32, 35, 30, 32, 29, and 32, respectively). bid, twice daily; bsa, body surface area; itt, intent-to-treat; mitt, modified intent-to-treat; nrs, numeric rating scale; pasi, psoriasis area and severity index; pga, physician global assessment; qd, once daily; sd, standard deviation. pga response rates ■ primary endpoint: pga response rates (defined as pga score 0 or 1 and ≥2-grade improvement) at week 12 were significantly higher (at 0.05 significance level) in the tapinarof cream groups than the vehicle groups (65% [1% bid], 56% [1% qd], 46% [0.5% bid], 36% [0.5% qd] vs 11% [vehicle bid] and 5% [vehicle qd]) and were maintained for 4 weeks after the end-of-study treatment in all active treatment groups except for the 0.5% bid group2 pga response rates by baseline % bsa affected ■ pga response rates at week 12 were higher in tapinarof cream groups than vehicle groups, regardless of baseline % bsa affected (figure 2) – 1 to <10% bsa affected (n=102): 67% (1% bid), 60% (1% qd), 33% (0.5% bid), and 35% (0.5% qd) vs 13% (vehicle bid) and 6% (vehicle qd) – ≥10% bsa affected (n=39): 64% (1% bid), 40% (1% qd), 75% (0.5% bid), and 38% (0.5% qd) vs 0% (vehicle bid) and 0% (vehicle qd) figure 2. proportion of subjects who achieved pga response* at week 12 by % bsa affected at baseline 67 60 33 35 13 6 64 40 75 38 0 n=3n=4n=8n=8n=5n=11n=17n=15n=20n=18n=20n=12 0 p ro p o rt io n o f su b je ct s, % bsa affected, % 60 80 100 40 20 0 1% to <10% ≥10% tapinarof 1% bid tapinarof 1% qd tapinarof 0.5% bid tapinarof 0.5% qd vehicle bid vehicle qd n is number of subjects with available results at week 12. *defined as pga score 0 or 1 (clear or almost clear) and ≥2-grade improvement from baseline. bid, twice daily; bsa, body surface area; pga, physician global assessment, qd, once daily. pga response rates by baseline duration of psoriasis ■ pga response rates at week 12 were higher in tapinarof cream groups than in vehicle groups, regardless of baseline duration of psoriasis, except for the 0.5% bid treatment group in the 5 years to <10 years subgroup (figure 3) – 6 months to <5 years (n=27): 50% (1% bid), 80% (1% qd), 50% (0.5% bid), and 29% (0.5% qd) vs 0% (vehicle bid) and 0% (vehicle qd) – 5 years to <10 years (n=32): 67% (1% bid), 50% (1% qd), 20% (0.5% bid), and 50% (0.5% qd) vs 25% (vehicle bid) and 0% (vehicle qd) – ≥10 years (n=82): 73% (1% bid), 50% (1% qd), 53% (0.5% bid), and 33% (0.5% qd) vs 8% (vehicle bid) and 8% (vehicle qd) figure 3. proportion of subjects who achieved pga response* at week 12 by duration of psoriasis at baseline 50 80 50 29 0 0 0 p ro p o rt io n o f su b je ct s, % duration of psoriasis 60 80 100 40 20 0 6 months to <5 years 5 years to <10 years ≥10 years n=6 n=5 n=4 n=7 n=3 n=2 67 50 20 50 25 n=6 n=6 n=5 n=6 n=4 n=5 73 50 53 33 8 8 n=11 n=14 n=17 n=15 n=12 n=13 tapinarof 1% bid tapinarof 1% qd tapinarof 0.5% bid tapinarof 0.5% qd vehicle bid vehicle qd n is number of subjects with available results at week 12. *defined as pga score 0 or 1 (clear or almost clear) and ≥2-grade improvement from baseline. bid, twice daily; pga, physician global assessment, qd, once daily. pga response rates by fitzpatrick skin type ■ pga response rates at week 12 were higher in tapinarof cream groups than vehicle groups, regardless of fitzpatrick skin type (figure 4) – fitzpatrick skin type i/ii (n=41): 60% (1% bid), 67% (1% qd), 50% (0.5% bid), and 25% (0.5% qd) vs 0% (vehicle bid) and 10% (vehicle qd) – fitzpatrick skin type iii/iv (n=73): 54% (1% bid), 47% (1% qd), 60% (0.5% bid), and 44% (0.5% qd) vs 18% (vehicle bid) and 0% (vehicle qd) – fitzpatrick skin type v/vi (n=27): 100% (1% bid), 75% (1% qd), 25% (0.5% bid), and 25% (0.5% qd) vs 0% (vehicle bid) and 0% (vehicle qd) figure 4. proportion of subjects who achieved pga response* at week 12 by fitzpatrick skin type 60 67 50 25 0 10 0 p ro p o rt io n o f su b je ct s, % fitzpatrick skin type 60 80 100 40 20 0 i/ii iii/iv v/vi tapinarof 1% bid tapinarof 1% qd tapinarof 0.5% bid tapinarof 0.5% qd vehicle bid vehicle qd n=5 n=6 n=8 n=8 n=4 n=10 54 47 60 44 18 n=13 n=15 n=10 n=16 n=11 n=8 100 75 25 25 0 0 n=5 n=4 n=8 n=4 n=4 n=2 n is number of subjects with available results at week 12. *defined as pga score 0 or 1 (clear or almost clear) and ≥2-grade improvement from baseline. bid, twice daily; pga, physician global assessment, qd, once daily. safety ■ treatment-emergent aes (teaes) were mostly mild to moderate in severity ■ the most common treatment-related teaes were folliculitis (10% tapinarof vs 1% vehicle), contact dermatitis (3%; all tapinarof), and headache (1%; all tapinarof) ■ incidence and type of aes were generally comparable across subgroups and consistent with those observed in the overall population conclusions ■ overall, tapinarof cream was efficacious and well tolerated regardless of baseline % bsa affected, psoriasis duration, and fitzpatrick skin type ■ higher pga response rates at week 12 were observed in the 1% qd tapinarof cream group vs vehicle across all subgroups ■ these findings support the previously reported efficacy and safety outcomes of the overall population2,3 ■ a phase 3 study of tapinarof cream 1% qd in psoriasis is ongoing references 1. menter a et al. j am acad dermatol. 2008;58:829–850; 2. robbins k et al. j am acad dermatol. 2019;80:714–721; 3. bhatia n et al. skin. 2018;2:s85; 4. gisondi p et al. int j mol sci. 2017;18:2427; 5. alexi af, blackcloud p. j clin aesthet dermatol. 2014;7:16–24. acknowledgments the authors thank the participating investigators, patients and their families, and colleagues involved in the conduct of the study. editorial and medical writing support under the guidance of the authors was provided by apothecom, uk, and was funded by dermavant sciences, inc. in accordance with good publication practice (gpp3) guidelines (ann intern med. 2015;163:461–464). contact dr mark lebwohl at lebwohl@aol.com with questions or comments. skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 119 in-depth reviews psoriasis in pregnancy: a review michael tyutyunik1, nahla shihab md2, mark lebwohl md3 1research assistant, department of dermatology, icahn school of medicine at mount sinai, new york, ny 2clinical dermatology fellow, department of dermatology, icahn school of medicine at mount sinai, new york, ny 3professor and chairman, department of dermatology, icahn school of medicine at mount sinai, new york, ny psoriasis is chronic inflammatory skin disease that most commonly characterized by silvery scale erythematous plaque.1,2 it may be associated with other comorbidities such as joint, ocular, and systemic disorders. the treatment of psoriasis is varied depending on the disease severity, comorbidities, and patient preference.2,3 in the case of pregnancy, treatment of psoriasis can also be challenging. generally psoriasis improves during pregnancy, however, many pregnant patients still need treatment. pregnant women must use caution when using any medications, and doctors must decide what treatment options are best for mother and fetus.4 immunopathology of psoriasis psoriasis is a complex autoimmune and autoinflammatory disease that is characterized by rapid epidermal growth resulting in a number of clinical manifestations, most commonly sharply demarcated erythematous scaling plaques.5 the major cells that play a central role in the pathogenesis of psoriasis are keratinocytes, endothelium, dendritic cells, and t cells.6 alteration of keratinocyte function, vascular structure, innate and adaptive immune systems contribute to the manifestations of psoriasis.7 dendritic cells are a key factor of inflammation in psoriasis, in particular, plasmacytoid dendritic cells producing interferon-alpha (ifn-alpha), which stimulate the activation of myeloid dendritic cells. myeloid dendritic cells produce interleukinintroduction review psoriasis is a complex autoimmune disease, most commonly characterized by silvery scale erythematous plaque. during pregnancy, there is a physiologic change of immunology status, which shifts from an inflammatory state to an anti-inflammatory state, in order to avoid fetal rejection. as a result of this immunomodulatory changes, the majority of pregnant patients experience improvement of their psoriasis. the treatment of psoriasis in pregnancy can be challenging, mainly because there is only a few evidence-based studies. the objective of this paper is to review the relevant data on psoriasis in pregnancy and its treatment. abstract skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 120 12 (il-12) and il-23, which promote the development of t-helper 1 (th1) and th17 cells.6,7 th1 cells produce proinflammatory cytokines, including ifn-gamma, il-2, and tumor necrosing factor-alpha (tnf-alpha), that have roles in inflammation and psoriasis-like changes in skin. the activation of th17 cells stimulates the production of il17a and il-22, both of them promoting keratinocyte activation and growth.7 recent data suggest il-17 cytokines as key factors in the development of psoriasis. immunological changes during pregnancy the state of pregnancy has the potential to be severely detrimental to the female immune system being that the father's foreign antigens, which are contained within the fetus, are capable of eliciting a robust immunological response from the mother. it follows, therefore, that during pregnancy, the mother’s immune responses must shift from an inflammatory state to an antiinflammatory state, in order to avoid fetal rejection.8 pregnant women experience an overall increase in white blood cells, mainly neutrophils. however, there is a decrease in total t cell numbers and activated t cells 9 characteristics of psoriasis in pregnancy as a result of immunomodulatory changes of pregnancy, the majority of pregnant patients experience improvement of their psoriasis. however, some may also experience worsening of psoriasis, which is still poorly understood.10 in pregnancy, the maternal immune system is shifting toward th2 immunity, causing a lower level of th1 cytokines that are responsible for the inflammatory immune response in psoriasis.11 psoriasis is also correlated with hormonal changes that women undergo during pregnancy, with high level of estrogen and progesterone as the central players for improvement.12,13 throughout pregnancy other hormones including human chorionic gonadotropin, glucocorticoid, prolactin, and human placental lactogen, are increased. these hormones are all known to have immunosuppressive effects, which is also a reason for improvement of psoriasis in pregnancy.10,14 psoriasis treatment in pregnancy there are few evidence-based studies on treating psoriasis in pregnancy. topical treatments are the most commonly recommended treatment options for pregnant women with psoriasis.15 moisturizing agents and emollients such as petroleum jelly and mineral oil have been found to reduce psoriatic plaques. they can help reduce inflammation of the skin, reduce skin cell generation, and clear affected skin plaques. topical corticosteroids are first line therapy for psoriasis in pregnant patients.16 nonetheless, there is always a risk of systemic absorption which may vary from 0.5 to 7% in intact skin, and may be greater in inflamed or damaged skin.17 therefore, it is recommended to use low to moderate potency corticosteroids rather than potent and very potent corticosteroids in pregnant woman with psoriasis.18 other common topical treatments in psoriasis including salicylic acid, coal tar and tazarotene, are not recommended during pregnancy.16 calcipotriene is also not recommended in pregnancy (pregnancy category c). however, if there is no other alternative treatment, limited use of topical calcipotriene is still permissible.19 skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 121 phototherapy with narrowband ultraviolet b (nb-uvb) is the second-line treatment for pregnant women with psoriasis.20 uvb, which is present in natural sunlight, is an effective treatment for psoriasis as the light can penetrate the layers of the skin and help reduce the growth of affected skin cells. phototherapy, both narrowband and broadband uvb, is considered safe and effective in pregnancy due to limited penetration to the mother’s skin.21 the data for phototherapy during pregnancy are limited, nevertheless it has not been associated with any increase risk of abnormal delivery or fetal abnormalities.20 the only consideration of phototherapy in pregnancy is the potential photodegradation of maternal folate, which can cause neural tube defects in the fetus. therefore, folic acid supplementation is even more highly recommended for these patients.22 nowadays biologic agents are the cornerstones in the treatment of psoriasis. although this treatment shows promise in treating the disease, the risk of alteration of the immune system is the major concern particularly in pregnant patient.23 currently there are four classes of biologic agents that are approved for psoriasis, tumor necrosis factor inhibitors (tnfi), an il-12/23 inhibitor, il-17 inhibitors, and il-23 inhibitors. fundamentally, these therapies are monoclonal antibodies or fusion proteins which block cytokines or receptors associated with psoriasis, which play roles in the pathogenesis of psoriasis.23 the potential antibody transfer from mother to fetus is the major concern that limits the use of biologic agents in pregnancy. monoclonal antibody can actively cross the placenta with the help of neonatal fragment crystallizable (fc) receptor that are found on trophoblasts, especially during second and third trimesters.24 this transfer may result in immunosuppression of the newborn, resulting in higher risk for infection. however, pregnant women are usually excluded from clinical trials including study for biologic agents. therefore, knowledge about safety of these treatments are very limited.25 among tnfi, certolizumab pegol is the only biologic agent that has supporting data of safety to be used in both pregnancy and breastfeeding, due to its lack of fc portion. without the fc portion, certolizumab is not actively transported across the placenta.26 ustekinumab, an il-12/23 inhibitor, has very limited data with only few case reports and case series that showed no increased risk of congenital defects or adverse events in pregnant women.27 both il-17 inhibitors (secukinumab, ixekizumab), and il-23 inhibitors (tildrakizumab, guselkumab, risankizumab) have extremely limited data with no human studies for psoriasis in pregnancy. psoriasis is a chronic skin condition with a variety of treatments that impacts conception, pregnancy, and postpartum care. while there are some treatments already known to be safer than others, the precise effects of psoriasis on pregnancy are still mostly incomplete due to insufficient available studies. a large scale of systematic review in the treatment of psoriasis in pregnancy is still needed. conclusion skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 122 conflict of interest disclosures: none funding: none corresponding author: nahla shihab, md department of dermatology, icahn school of medicine at mount sinai, new york, ny 5 e 98th street, new york, ny, 10029 phone: 212-241-9728 fax: 212-987-1197 email: nahla.shihab@gmail.com references: 1. krueger gg, feldman sr, camisa c, duvic m, elder jt, gottlieb ab, koo j, krueger jg, lebwohl m, lowe n, menter a. two considerations for patients with psoriasis and their clinicians: what defines mild, moderate, and severe psoriasis? what constitutes a clinically significant improvement when treating psoriasis? journal of the american academy of dermatology. 2000 aug 1;43(2): 281-5. 2. feldman sr. epidemiology, clinical, manifestations, and diagnosis of psoriasis. [updated 2019 aug 6]. in: uptodate [internet]. available from: https://www.uptodate.com/contents/epidemiology -clinical-manifestations-and-diagnosis-ofpsoriasis (accessed 31 october 2019). 3. lebwohl m, ting pt, koo jy. psoriasis treatment: traditional therapy. annals of the rheumatic diseases. 2005 mar 1;64(suppl 2): ii836. 4. janssen nm, genta ms. the effects of immunosuppressive and anti-inflammatory medications on fertility, pregnancy, and lactation. archives of internal medicine. 2000 mar 13;160(5): 610-9. 5. ryan s. psoriasis: characteristics, psychosocial effects and treatment options. british journal of nursing. 2008 mar 13;17(5): 284-90. 6. reali e, brembilla nc. editorial: immunology of psoriatis disease.frontiers in immunology. 2019 mar 29;10(657):1-3. 7. blauvelt a, ehst b. patophysiology of plaque psoriasis. [updated 2019 apr 30]. in: uptodate [internet]. available from: https://www.uptodate.com/contents/ pathophysiology-of-plaque-psoriasis (accessed 31 october 2019). 8. robinson, d. p., & klein, s. l. (2012). pregnancy and pregnancy-associated hormones alter immune responses and disease pathogenesis. hormones and behavior, 62(3), 263-271. 9. maclean ma, wilson r, thomson ja, krishnamurthy s, walker jj. immunological changes in normal pregnancy. european journal of obstetrics & gynecology and reproductive biology. 1992 feb 28;43(3): 167-72. 10. hoffman mb, farhangian m, feldman s. psoriasis during pregnancy: characteristics and important management recommendations. expert rev. clin. immunol. 11(6), 709–720 (2015) 11. yip l, mccluskey j, sinclair r. immunological aspects of pregnancy. clin dermatol 2006;24(2):84-7 12. boyd as, morris lf, phillips cm, et al. psoriasis and pregnancy: hormone and immune system interaction. int j dermatol 1996;35(3):169-72 13. murase je, chan kk, garite tj, cooper dm, weinstein gd. hormonal effect on psoriasis in pregnancy and post-partum. archives of dermatology. 2005 may 1;141(5): 601-6. 14. nolten we, rueckert pa. elevated free cortisol index in pregnancy: possible regulatory mechanisms. am j obstet gynecol 1981;139(4):492-8 15. weatherhead s, robson sc, reynolds nj. management of psoriasis in pregnancy. bmj. 2007 jun 7;334(7605): 1218-20. 16. bae ys, van voorhees as, hsu s, et al. review of treatment options for psoriasis in pregnant or lactating women: from the medical board of the national psoriasis foundation. j am acad dermatol 2012; 67(3):459-77 17. dhar s, seth j, parikh d. systemic side-effects of topical corticosteroids. indian j dermatol 2014;59(5):460-4 18. chi cc, kirtschig g, aberer w, et al. evidencebased (s3) guideline on topical corticosteroids in pregnancy. br j dermatol. 2011;165(5): 943–952 19. murase je, heller mm, butler dc. safety of dermatologic medications in pregnancy and lactation: part i. pregnancy. j am acad dermatol. 2014;70(3):401. e1–e14 20. vena ga, cassano n, bellia g, colomb\o d. psoriasis in pregnancy: challenges and solutions. psoriasis: targets and therapy 2015;5:83-95. 21. lam j, polifka je, dohil ma. safety of dermatologic drugs used in pregnant patients with psoriasis and other inflammatory skin diseases. j am acad dermatol 2008;59(2):295315 22. el-saie lt, rabie ar, kamel mi, seddeik ak, elsaie ml. effect of narrowband ultraviolet b phototherapy on serum folic acid levels in patients with psoriasis. lasers med sci. 2011;26(4):481–485. skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 123 23. emer jj, frankel a, zeichner ja. a practical approach to monitoring patients on biological agents for the treatment of psoriasis. the journal of clinical and aesthetic dermatology. 2010 aug;3(8): 20. 24. story, c.m. a major histocompatibility complex class i-like fc receptor cloned from human placenta: possible role in transfer of immunoglobulin g from mother to fetus. j. exp. med. 1994, 180, 2377–81 25. porter ml, lockwood sj, kimball ab. update on biologic safety for patients with psoriasis during pregnancy. int j womens dermatol 2017;3:21–5. 26. european medicines agency. certolizumab pegol (cimzia) summary of product characteristics [internet]. [cited 2019 november 8]. available from: https://www. ema.europa.eu/en/documents/productinformation/cimzia-eparproductinformation_en.pdf; 2019. 27. watson n, wu k, farr p, reynolds nj, hampton pj. ustekinumab exposure during conception and pregnancy in patients with chronic plaque psoriasis: a case series of 10 pregnancies. br j dermatol. 2018;180(1):195-6. powerpoint presentation • also at week 4, the proportion of patients achieving pga treatment success was higher in the cal/bdp pad-cream group (25.2%) compared to the vehicle group (0.6%) and numerically higher than the cal/bdp ts/gel group (18.7%; p=0.0510) (figure 2). • the patient reported ptcs score for cal/bdp pad-cream was rated superior to cal/bdp ts/gel at week 8 (p<0.0001) and was also significantly higher at week 4 (p<0.0001), demonstrating that cal/bdp pad-cream has superior treatment convenience compared to cal/bdp ts/gel. • the mean change in dermatology life quality index (dlqi) score from baseline to week 8 improved statistically significantly more in the cal/bdp pad-cream group compared to both vehicle (p<0.0001) and cal/bdp ts/gel (p=0.0110) (figure 3). a statistically significant difference was also observed at week 4 for cal/bdp pad-cream compared to vehicle (p<0.0001) and cal/bdp ts/gel (p=0.0159) (figure 3). • safety assessments during the trial demonstrated that cal/bdp pad-cream was well-tolerated with all adverse reactions reported at a frequency below 1%. • overall, 490 patients were randomised, 213 patients were in the cal/bdp padcream group, 209 patients were in the cal/bdp ts/gel group, and 68 patients were in the cream vehicle group. overall, all demographic characteristics were comparable between the three treatment groups (table 1). • the percentage mean change from baseline to week 8 in mpasi for cal/bdp pad-cream (67.5%) was superior compared to vehicle (11.7%; p<0.0001) and non-inferior to cal/bdp ts/gel (63.5%) (figure 1). results linda stein gold1, andreas pinter2, april armstrong3, lars iversen4, morten praestegaard4, matthias augustin5 1dermatology clinical research, henry ford health system, detroit, michigan, usa; 2dept. of dermatology, venereology and allergology, university hospital frankfurt/main, frankfurt/main, germany; 3keck school of medicine, department of dermatology, university of southern california los angeles, usa; 4mc2 therapeutics, hørsholm, denmark; 5university medical center hamburg-eppendorf, hamburg, germany phase 3 trial demonstrating high efficacy, favourable safety, and convenience of a novel calcipotriene and betamethasone dipropionate cream • the fixed dose combination of calcipotriene (cal 0.005% w/w, 50 µg/g) and betamethasone dipropionate (bdp 0.064% w/w, 0.5 mg/g as betamethasone) is a well-established treatment option for psoriasis based on strong scientific rationale for the single agents having complementary efficacy and safety. • cal/bdp pad-cream is an easily spreadable cream based on pad technology™, an innovative formulation and drug delivery system1. introduction • writing support was provided by anja snel-prentø, medlink. • the trial was funded by mc2 therapeutics. • pga, physician global assessment. mpasi, modified psoriasis area and severity index. dlqi, dermatology life quality index. bdp, betamethasone dipropionate. cal, calcipotriene. ptcs, psoriasis treatment convenience scale. *comparison of cal/bdp pad-cream to vehicle. **comparison of cal/bdp pad-cream to cal/bdp ts/gel. acknowledgements & abbreviations conclusions • cal/bdp pad-cream, an innovative topical treatment for plaque psoriasis based on pad technology, offers high efficacy combined with a favourable safety profile and a superior patient reported treatment convenience compared to cal/bdp ts/gel. methods • cal/bdp pad-cream was evaluated in a phase 3, multicentre, randomized, investigator-blind, active, and vehicle-controlled trial (nct03802344) enrolling 490 adult patients with mild to moderate psoriasis according to the physician global assessment (pga) scale. • the aim of the trial was to evaluate the efficacy and safety of cal/bdp padcream as well as treatment acceptability compared to cream vehicle and to cal/bdp topical suspension (ts)/gel (sourced in the eu as dovobet®/daivobet® gel). • patients applied trial medication once daily for up to 8 weeks. • the trial was conducted at 32 clinical sites across three european countries. • primary endpoint was percentage change in modified psoriasis area and severity index (mpasi) from baseline to week 8. • except for psoriasis treatment convenience scale (ptcs), the endpoints were analysed using the treatment-policy estimand for the full analysis set. as per protocol, the percentage change in mpasi from baseline to week 8 for cal/bdp pad-cream and the active comparator were first compared with cream vehicle for a superiority evaluation. also per protocol, cal/bdp pad-cream was next compared to active comparator for a non-inferiority evaluation. secondary endpoints were tested in a predefined testing hierarchy. multiple imputation for missing data was applied for endpoints, except for ptcs for which missing data was imputed using a last observation carried forward approach. figure 1. mpasi, percentage change from baseline figure 2. pga treatment success • at week 4, cal/bdp pad-cream demonstrated statistically significantly greater mean percentage change from baseline in mpasi compared to vehicle (p<0.0001) and to cal/bdp ts/gel (p=0.0006) (figure 1). • the proportion of patients achieving pga treatment success (2-step improvement to clear or almost clear) after 8 weeks was significantly greater for cal/bdp pad-cream (50.7%) compared to vehicle (6.1%, p<0.0001) and cal/bdp ts/gel (42.7%, p=0.0442) (figure 2). 1praestegaard m, steele f, crutchley n. polyaphron dispersion technology, a novel topical formulation and delivery system combining drug penetration, local tolerability and convenience of application. dermatol ther (heidelb). 2022 oct;12(10):2217-2231. references figure 3. mean change in dlqi 2023 winter clinical dermatology conference 25,7 54,6 62,6 67,5 23,4 46,3 56,7 63,5 6,4 11,5 12,4 11,7 0 10 20 30 40 50 60 70 80 0 1 2 3 4 5 6 7 8 m pa si m ea n pe rc en ta ge c ha ng e fr om b as el in e weeks cal/bdp cream cal/bdp gel vehicle p=0.1287** p=0.0006** p<0.0001* p<0.0001* 3,3 25,2 42,9 50,7 2,9 18,7 29,4 42,7 0 0,6 1,8 6,1 0 10 20 30 40 50 60 0 2 4 6 8 % p g a tr ea tm en t s uc ce ss weeks cal/bdp cream cal/bdp gel vehicle p=0.0442** p<0.0001* p=0.0510** -3,5 -5,6 -6,4 -2,9 -4,5 -5,3 -1,5 -2,1 -2,5 -7 -6 -5 -4 -3 -2 -1 0 0 2 4 6 8 ch an ge fr om b as el in e in d lq i weeks cal/bdp cream cal/bdp gel vehicle p<0.0001* p=0.0110** p<0.0001* p=0.0159** no subjects with pga success were observed at week 4 in the vehicle group. for this reason, statistical analysis of the difference between cal/bdp pad-cream and vehicle was inconclusive due to wide 95% confidence intervals, although substantial differentiation is demonstrated by the separation. a negative change from baseline indicates a decrease in dlqi , i.e., an improvement in the patient’s quality of life. cal/bdp cream (n=213) cal/bdp ts/gel (n=209) cream vehicle (n=68) mean age, years (sd) 48.6 (13.7) 51.5 (14.8) 50.8 (13.3) male, n (%) 136 (63.8%) 113 (54.1) 46 (67.6) mean pga (sd) 2.8 (0.4) 2.8 (0.4) 2.8 (0.5) mean mpasi (sd) 7.9 (4.0) 8.0 (3.8) 8.3 (3.8) mean dlqi 9.8 9.5 10.0 table 1. baseline demographics and characteristics dias nummer 1 skin may 2018 volume 2 issue 3 copyright 2018 the national society for cutaneous medicine 194 brief articles mislocalization of adherens junction-associated proteins in a patient with darier disease george d. glinos bs a , irena pastar phd a , marjana tomic-canic phd a , rivka c. stone, md phd a a department of dermatology and cutaneous surgery, university of miami miller school of medicine, miami, fl abstract darier disease (dd) is an autosomal dominant keratinizing genodermatosis that manifests clinically with red-brown pruritic papules in a seborrheic distribution often in association with palmoplantar pits and dystrophic nail changes. it is caused by mutation in atp2a2 which encodes a sarco/endoplasmic reticulum calcium atpase isoform 2 (serca2) pump that regulates calcium flux. consequent alteration of intracellular calcium homeostasis is thought to impair trafficking of cellular adhesion proteins and to lead to aberrant keratinocyte differentiation, contributing to the characteristic histopathologic features of acantholysis and dyskeratosis in dd, though the precise mechanisms are incompletely understood. previous studies have identified defective localization of desmosomal attachment proteins in skin biopsies and cultured keratinocytes from dd patients, but reports of effects on adherens junction proteins (including calcium-dependent e-cadherin) are conflicting. here we describe a case of dd presenting with characteristic clinical and histologic features in which we performed immunofluorescence staining of four adherens junction-associated proteins (ecadherin, α-catenin, β-catenin, and vinculin). in lesional (acantholytic) dd skin, we identified loss of distinctive bright membranous staining that was present at the periphery of keratinocytes throughout the epidermis in the healthy skin of a matched donor. perilesional (non-acantholytic) portions of dd skin partially recapitulated the normal phenotype. our findings support a role for serca2 dysfunction in impaired assembly of adherens junctions, which together with defective desmosomes contribute to acantholysis in dd. skin may 2018 volume 2 issue 3 copyright 2018 the national society for cutaneous medicine 195 darier disease (dd) (darier-white disease; keratosis follicularis) is a rare keratinizing genodermatosis with autosomal dominant inheritance and complete penetrance but variable expressivity 1 . dd manifests clinically as red-brown pruritic papules in a seborrheic distribution which often become secondarily infected and malodorous 1 , in association with palmoplantar pits and characteristic dystrophic nail changes 1,2 . dd is caused by mutation in atp2a2, which encodes sarco/endoplasmic reticulum calcium atpase isoform 2 (serca2), a pump located on the endoplasmic reticulum (er) membrane that regulates calcium flux 2,3 . consequent defective calcium homeostasis is thought to lead to impaired er trafficking of cellular adhesion proteins 2 , aberrant keratinocyte differentiation 2,4 , and disordered apoptosis 2,3 . these defects may account for the histologic findings in dd: acantholysis, leading to the formation of suprabasal clefts 2,3 , and dyskeratosis, with presence of corps ronds and grains 2,3 . prior studies have reported loss of membranous localization of desmosomal proteins in acantholytic dd lesions as well as in dd keratinocytes ex vivo, but conflicting findings have been reported for adherens junctionassociated proteins 5-7 . here we describe a case of dd with characteristic clinical presentation and histologic features on skin biopsy, in which we performed immunofluorescence staining of several adherens junction proteins in order to further characterize the in vivo effects of serca2 dysfunction on their cellular localization. a 61 year old caucasian man presented to our clinic for evaluation of a chronic eruption on the chest and legs that had appeared 15 years prior and had worsened over the preceding 3 years. the eruption was pruritic, exacerbated by heat and friction, and had not been previously treated. he also complained of fragile nails that broke easily with minimal trauma. family history was notable for a similar eruption in the patient’s father and paternal grandfather. physical examination revealed erythematous keratotic crusted papules on the chest and back, excoriated lichenified plaques on the legs, and verrucous papules over the shins. white and red longitudinal bands in association with splitting, ridging, and distal v-nicking were observed on the nail plates of multiple fingernails (figure 1). bacterial cultures of the lesions grew s. aureus. biopsies of involved skin on the chest, back, and legs revealed suprabasal acantholysis with dyskeratosis (figure 2), and a diagnosis of dd was made. immunofluorescence staining of four cellular adherens junction-associated proteins (αcatenin, β-catenin, intracellular (cytoplasmic) tail of e-cadherin, and vinculin) was performed on formalin-fixed paraffinembedded sections from the patient’s biopsy specimen featuring “lesional” acantholytic clefting in association with histologically normal-appearing “perilesional” skin (figure 3). localization of each protein in lesional and perilesional dd was compared with localization in normal skin obtained from an ageand gendermatched healthy control. in the healthy control, e-cadherin, α-catenin, and β-catenin were localized to the cell membrane as expected, displaying a “chicken wire” pattern of uniformly bright staining around the keratinocyte borders. vinculin localized to the membrane and perinuclear areas with a thicker peripheral staining. in contrast, in dd, the intracellular introduction case report skin may 2018 volume 2 issue 3 copyright 2018 the national society for cutaneous medicine 196 portion of e-cadherin displayed intense membranous and associated diffuse cytoplasmic staining at the acantholytic cleft, with loss of membranous staining and faint cytoplasmic staining in the underlying epidermis. perilesional skin showed restoration of membranous staining throughout the epidermis, with enhanced staining intensity of keratinocytes below the stratum corneum. similar patterns were observed for αand β-catenin, with more subtle signal enhancement in the upper portion of the epidermis. vinculin remained perinuclear in lesional skin but there was loss of distinct strong peripheral staining, which was recapitulated in keratinocytes of lower portions of the epidermis in perilesional skin. management options for dd were discussed with the patient. he declined treatment with systemic retinoids due to concern over medication toxicities. he deferred genetic testing for himself and for other family members because of financial considerations. he was given a 1-week course of oral antibiotics for impetiginization. topical triamcinolone 0.1% ointment was initiated to involved areas on the chest in combination with tretinoin 0.025% ointment to lichenified lesions on the legs. the patient was satisfied with his response to this regimen and was subsequently lost to follow-up. figure 1. darier disease skin and nail findings. (a) red-brown keratotic coalescing papules in a seborrheic distribution. (b) red and white longitudinal bands, splitting, and distal v shaped nicks were most apparent in the nail plates of the patient’s right hand. skin may 2018 volume 2 issue 3 copyright 2018 the national society for cutaneous medicine 197 figure 2. (a) histologic findings in dd skin lesions. predominant features include (b) acantholysis with suprabasal clefting (star) and (c) dyskeratosis with presence of epidermal corps ronds (arrow) and grains. a. b. c. . skin may 2018 volume 2 issue 3 copyright 2018 the national society for cutaneous medicine 198 figure 3. adherens junction-associated proteins in dd. immunofluorescence staining of e-cadherin, α-catenin, β-catenin, and vinculin in healthy donor skin, in dd lesional (acantholytic) skin, and in perilesional (non-acantholytic) dd skin. original magnification 20x; scale bars = 100μm. skin may 2018 volume 2 issue 3 copyright 2018 the national society for cutaneous medicine 199 despite its rarity, dd has been well described in the medical literature for over 100 years. the causal atp2a2 mutation is known, but the pathophysiologic impact on clinical phenotype is incompletely understood 3 . one proposed mechanism is that reduced ca 2+ influx into the er lumen induces a stress response, which causes mis-folding and impaired cellular trafficking of proteins 2 . this has been supported by studies in dd keratinocytes demonstrating constitutive er stress in association with cytoplasmic retention of junctional proteins and formation of immature adhesion complexes 6 . in fact, the loss of membranous localization of desmosomal attachment plaque proteins (e.g. desmoplakins, plakophilin, plakoglobin) as well as desmosomal cadherins (desmoglein 1/3, desmocollin 1) has been well-described in acantholytic portions of histologic sections from dd skin biopsies 5,7,8 , with normal localization maintained in perilesional skin 5 as well as relative maintenance of tight junctions 8 . however, there are conflicting reports regarding preservation versus loss of adherens junction protein localization in dd 5,6,8 . in healthy skin, in response to calcium flux, the cytoplasmic (intracellular) tail of e-cadherin interacts with β-catenin which binds to α-catenin, associating ecadherin with actin-binding proteins including vinculin to link the cytoskeleton and produce intercellular adhesion 9 . in contrast with previous findings of preserved membranous staining of e-cadherin, αand β-catenin throughout the dd epidermis 5 , we observed alterations in the localization of these proteins in our patient, with intense membranous and cytoplasmic staining at the acantholytic cleft and dim diffuse cytoplasmic staining below. interestingly, while the membranous staining was maintained in healthy-appearing perilesional skin, there was enhanced intensity at the superior portion of the epidermis, perhaps indicating keratinocytes at the threshold of acantholysis and cleft formation. we similarly observed reduced peripheral staining of vinculin in lesional skin as well as in pre-acantholytic superior portion of perilesional skin. though our study is limited to observations in a single patient, our findings support a role for serca2 dysfunction in the impaired cellular trafficking of at least four adherens junctionassociated proteins which contributes to the loss of cell-to-cell adhesion in dd. further studies in additional dd patients are warranted to confirm our findings. acknowledgments: the authors acknowledge dr. rw keane, dr. jp vaccari, and mr. ap sawaya for their assistance with fluorescence image capturing. conflict of interest disclosures: none funding: none corresponding author: rivka c. stone, md, phd department of dermatology and cutaneous surgery university of miami miller school of medicine 1600 nw 10 th ave, rmsb 2029a miami, fl 33136 305-243-7295 (office) rivka.stone@med.miami.edu discussion skin may 2018 volume 2 issue 3 copyright 2018 the national society for cutaneous medicine 200 references: 1. burge sm, wilkinson jd. darier-white disease: a review of the clinical features in 163 patients. j am acad dermatol. 1992;27(1):40-50. 2. savignac m, edir a, simon m, hovnanian a. darier disease : a disease model of impaired calcium homeostasis in the skin. biochim biophys acta. 2011;1813(5):11111117. 3. takagi a, kamijo m, ikeda s. darier disease. j dermatol. 2016;43(3):275279. 4. elias pm, ahn sk, denda m, et al. modulations in epidermal calcium regulate the expression of differentiation-specific markers. j invest dermatol. 2002;119(5):11281136. 5. hakuno m, shimizu h, akiyama m, et al. dissociation of intraand extracellular domains of desmosomal cadherins and e-cadherin in hailey-hailey disease and darier's disease. br j dermatol. 2000;142(4):702-711. 6. savignac m, simon m, edir a, guibbal l, hovnanian a. serca2 dysfunction in darier disease causes endoplasmic reticulum stress and impaired cell-tocell adhesion strength: rescue by miglustat. j invest dermatol. 2014;134(7):1961-1970. 7. burge sm, garrod dr. an immunohistological study of desmosomes in darier's disease and hailey-hailey disease. br j dermatol. 1991;124(3):242-251. 8. raiko l, leinonen p, hagg pm, peltonen j, oikarinen a, peltonen s. tight junctions in hailey-hailey and darier's diseases. dermatol reports. 2009;1(1):e1. 9. wheelock mj, johnson kr. cadherins as modulators of cellular phenotype. annu rev cell dev biol. 2003;19:207235. skin may 2018 volume 2 issue 3 copyright 2018 the national society for cutaneous medicine 201 immunofluorescence staining 8 μm thick formalin-fixed, paraffin-embedded tissue sections from skin biopsies were de-paraffinized with xylene (emd, gibbstown, nj) and rehydrated. for antigen retrieval, sections were heated at 95°c in 0.01 m sodium-citrate solution (sigma-aldrich, st. louis, mo) for 30 minutes. sections were blocked with 5% bovine serum albumin (bsa; sigma-aldrich, st. louis, mo), and separate sections were subsequently incubated overnight with anti-vinculin (v9131; sigma-aldrich, st. louis, mo), anti-αcatenin (ab3236; cell signaling technology, danvers, ma), anti-β-catenin (ab9587s; cell signaling techology, danvers, ma), and anti-e-cadherin (ab610181; bd biosciences, san jose, ca) primary antibodies. signal was visualized with anti-rabbit and anti-goat alexa-fluor 488 secondary antibodies (invitrogen, carlsbad, ca) diluted 1:500 in bsa. slides were mounted with media containing 4’,6diamidino-2-phenylindole (dapi; vector laboratories, burlingame, ca) to visualize cell nuclei. images were captured with the evos fl auto imaging system/evos fl auto software (thermo fisher scientific, waltham, ma). skin specimens skin biopsies from a patient with darier disease were initially obtained for diagnostic purposes after informed consent was obtained, and the patient further consented to the use of these specimens for immunofluorescence staining as well as to the use of the clinical images in this study. healthy human skin was obtained after informed consent from a donor undergoing an elective surgery, with approval of the university of miami institutional review board (protocol# um20070922). supplementary material: methods introduction • atopic dermatitis (ad) is a chronic, pruritic skin disease characterized by type 2 immune-mediated infl ammation and skin barrier dysfunction1 • in a recent large-scale rna-sequencing-based transcriptomic study of ad, psoriasis, and matched control samples, it was found that the type 2 cytokine interleukin 13 (il13) was the most distinctive marker for ad2 — increased expression levels of il13 were found in both lesional and nonlesional ad skin — expression levels of il13 in lesional ad skin correlated with disease severity • in contrast, expression of the type 2 cytokine il4 was detectable in 40% of the ad skin samples and at very low expression levels • il-13 has been shown to modulate the expression of infl ammatory mediators, such as chemokines, and skin barrier markers related to the pathophysiology of ad3-8 • tralokinumab is a fully human igg4 monoclonal antibody in phase 3 development for ad that specifi cally neutralizes il-139 methods study population participants • adult patients with a history of ad for at least 3 years — the same ad cohort as reported by tsoi et al from their large-scale transcriptomic study of ad2 • adult volunteers without personal or familial history of allergic atopic and chronic infl ammatory diseases inclusion criteria • dermatologist-confi rmed diagnosis of ad (diagnosed on the basis of a skin examination by experienced dermatologists according to standard criteria for ad [american academy of dermatology consensus criteria]) exclusion criteria • any other chronic skin disease • systemic treatment with immune-e� cient medication • topical treatment within 1 week prior to material sampling results atopic dermatitis disease biomarkers strongly correlate with il-13 levels, are regulated by il-13, and are modulated by tralokinumab in vitro stephan weidinger,1 maxim a.x. tollenaere,2 katharina drerup,1 thomas litman,2 hanne norsgaard2 1department of dermatology and allergy, university hospital schleswig-holstein, campus kiel, kiel, germany; 2skin research, leo pharma a/s, ballerup, denmark objectives • to examine the correlation of il13 expression with ad disease biomarkers by use of rna-sequencing data from ad lesional skin samples • to investigate il-13-mediated regulation of ad disease biomarkers and their modulation by tralokinumab in primary cultures of human keratinocytes and dermal fi broblasts conclusions • il13 expression levels correlate strongly with disease severity and with biomarkers related to the pathophysiology of ad • the expression of several ad disease biomarkers is regulated by il-13 and is normalized in a dose-dependent manner by tralokinumab in cultures of human keratinocytes and dermal fi broblasts • these fi ndings support the rationale for neutralizing excessive levels of il-13 in ad by utilizing monoclonal antibodies targeting il-13, such as tralokinumab references 1. weidinger s et al. nat rev dis primers 2018;4:1 2. tsoi lc et al. j invest dermatol 2019;139:1480–1489 3. purwar r et al. j invest dermatol 2006;126:1043–1051 4. fukuda k et al. j allergy clin immunol 2003;111:520–526 5. matsumura s et al. j dermatol sci 2015;78:215–223 6. kim be et al. clin immunol 2008;126:332–337 7. pellerin l et al. j allergy clin immunol 2013;131:1094–1102 8. berdyshev e et al. jci insight 2018;3:pii 98006 9. popovic b et al. j mol biol 2017;429:208–219 disclosures • stephan weidinger is a speaker, advisory board member, and/or investigator for: abbvie; galderma; incyte; kymab; la roche-posay; leo pharma; lilly; novartis; pfi zer; and regeneron and sanofi -genzyme • maxim a.x. tollenaere, thomas litman, and hanne norsgaard are employees of leo pharma • katharina drerup has nothing to disclose acknowledgments • re-analysis of rna-sequencing data and in vitro studies were performed by leo pharma • this presentation is sponsored by leo pharma • medical writing support was provided by stephanie rippon, phd, and amy graham, phd, from mccann health, funded by leo pharma table 1. patient samples included in the study ad controls (healthy) number of individuals (male/female) 27 (12/15) 38 (16/22) age, years, mean (sd) 34.07 (10.96) 32.63 (11.64) objective scorad,* mean (sd) 31.11 (10.96) flg mutation carriers 5 1 *objective scorad does not include the subjective items daily pruritus and sleeplessness. flg, fi laggrin; objective scorad, objective component of scoring atopic dermatitis; sd, standard deviation. figure 1. study design in silico bioinformatics analysis of rna-sequencing data2 to examine the correlation between il13 expression and ad disease biomarkers validate correlations in vitro using disease-relevant cell cultures can il-13-driven expression of ad disease biomarkers be reverted by tralokinumab? human keratinocytes human dermal fibroblasts figure 2. il13 expression strongly correlates with key ad disease biomarkers: a) positive correlation between il13 expression and infl ammatory mediators and b) negative correlation between il13 expression and skin barrier markers 2 7 6 5 4 3 a b il13 –5 –4 –3 –2 –1 0 1 2 c c l2 2 il13 –6 210–1–2–3–4–5 c c l2 2 7 6 5 4 3 il13 –4 210–1–2–3 c c l1 7 7 –5 –3 –1 1 3 5 pearson r=0.79 pearson r=0.69 il13 –4 210–1–2–3 n tr k 1 5 –7 –5 –3 –1 1 3 pearson r=0.82 il13 –4 210–1–2–3 fl g 2 14 9 10 11 12 13 pearson r=-0.61 il13 –4 210–1–2–3 el o v l6 7 4 5 6 pearson r=-0.73 il13 –4 210–1–2–3 fl g 16 10 11 12 13 14 15 pearson r=-0.55 il13 –4 210–1–2–3 lo r 10 5 6 7 8 9 pearson r=-0.59 pearson r=0.81 graph axes represent log2 (cpm) values. ccl, c-c motif chemokine ligand; cpm, counts per million; elovl, elongation of very long chain fatty acids; il, interleukin; lor, loricrin; ntrk, neurotrophic tyrosine kinase. figure 3. tralokinumab inhibits il-13-induced expression of the chemokine ccl-2 in human dermal fi broblasts: a) ccl-2 protein concentration in supernatant; b) percentage inhibition of il-13-induced ccl-2 protein secretion; c) ccl2 mrna expression; and d) percentage inhibition of il-13-induced ccl2 mrna expression ll o d ccl-2 protein in supernatant igg4 isotype control tralokinumab c c l2 p g /m l � s d a tralokinumab (nm) tralokinumab (nm) 150 0 50 100 150 0 50 100 antibody (nm) 0.01 1 100 % in h ib it io n � s d b c d % in h ib it io n � s d antibody (nm) 0.01 1 100 0 400 300 200 100 c o n tr o l 3010 31 0 .30 .1 0 .0 3 0 .0 1 0 .0 0 30 b a se lin e le ve l ccl2 mrna fo ld -c c l2 e xp re ss io n � s d 0 10 8 6 4 2 c o n tr o l 3010 31 0 .30 .1 0 .0 3 0 .0 1 0 .0 0 30 rhil-13 rhil-13 ic 50 : 335 pm ic 50 : 467 pm cells were stimulated with 2 ng/ml (0.16 nm) rhil-13. n=1 experiment. 1 nm of antibody=0.15 µg/ml. mean change � sd. ic 50 , half maximal inhibitory concentration; llod, lower limit of detection; mrna, messenger rna; rhil-13, recombinant human il-13. figure 4. tralokinumab inhibits il-13-induced expression of infl ammatory mediators in human keratinocytes: a) ccl-2 protein concentration in supernatant; b) percentage inhibition of il-13-induced ccl-2 protein secretion; c) ccl2 mrna expression; d) percentage inhibition of il-13-induced ccl2 mrna expression; e) ntrk1 mrna expression; and f) percentage inhibition of il-13-induced ntrk1 mrna expression fo ld -c c l2 e xp re ss io n � s em * fo ld -n tr k 1 e xp re ss io n � s em * ll o d ccl-2 protein in supernatant igg4 isotype control tralokinumab c c l2 p g /m l � s d a tralokinumab (nm) 150 0 –50 50 100 antibody (nm) 0.01 1 100 % in h ib it io n � s d b c d 0 200 150 100 50 c o n tr o l 3010 31 0 .30 .1 0 .0 3 0 .0 1 0 .0 0 30 rhil-13 ic 50 : 217 pm b a se lin e le ve l ccl2 mrna tralokinumab (nm) 150 0 –50 50 100 antibody (nm) 0.01 1 100 % in h ib it io n � s em * 0 30 20 10 c o n tr o l 3010 31 0 .30 .1 0 .0 3 0 .0 1 0 .0 0 30 rhil-13 ic 50 : 209 pm e f b a se lin e le ve l ntrk1 mrna tralokinumab (nm) 150 0 –50 50 100 antibody (nm) 0.01 1 100 % in h ib it io n � s em * 0 2000 500 1000 1500 20 10 c o n tr o l 3010 31 0 .30 .1 0 .0 3 0 .0 1 0 .0 0 30 rhil-13 ic 50 : 246 pm *n=3. cells were stimulated with 10 ng/ml (0.8 nm) rhil-13. n=3 experiments (� sem) and n=1 on protein measurement. 1 nm of antibody=0.15 µg/ml. sem, standard error of the mean. figure 5. tralokinumab restores expression of skin barrier markers decreased by il-13 in human keratinocytes: a) lor mrna expression; b) percentage inhibition of il-13-induced lor mrna suppression; c) flg mrna expression; d) percentage inhibition of il-13-induced flg mrna suppression; e) flg2 mrna expression; and f) percentage inhibition of il-13-induced flg2 mrna suppression fo ld -f lg e xp re ss io n � s d fo ld -f lg 2 e xp re ss io n � s d lor mrna igg4 isotype control tralokinumab fo ld -l o r e xp re ss io n � s d a tralokinumab (nm) 150 0 –50 50 100 antibody (nm) 1 10 100 % in h ib it io n � s d b c d c o n tr o l 10 05 025 12 .5 6. 25 3. 13 1. 5 6 0 .7 80 c o n tr o l 10 0502 5 12 .5 6. 25 3. 13 1. 56 0 .7 80 c o n tr o l 10 0502 5 12 .5 6. 25 3. 13 1. 56 0 .7 80 rhil-13 ic 50 : 11.4 nm b a se lin e le ve l b a se lin e le ve l flg mrna tralokinumab (nm) 150 0 –50 50 100 antibody (nm) 1 10 100 % in h ib it io n � s d rhil-13 ic 50 : 20.1 nm e f b a se lin e le ve l flg2 mrna tralokinumab (nm) 150 0 –50 50 100 antibody (nm) 1 10 100 % in h ib it io n � s d 0.0 1.5 0.5 1.0 0.0 1.5 0.5 1.0 0.0 1.5 0.5 1.0 rhil-13 ic 50 : 12.6 nm cells were stimulated with 50 ng/ml (4 nm) rhil-13. n=1 experiment. 1 nm of antibody=0.15 µg/ml. 39th annual fall clinical dermatology conference, october 17–20, 2019, las vegas, nv, usa. data previously presented at the 28th european academy of dermatology and venereology congress, october 9–13, 2019, madrid, spain 1. bickers dr, lim hw, margolis d, et al. j am acad dermatol. 2006; 55:490-500. 2. timms rm. psychol health med. 2013; 18(3):310–320. 3. revol o, milliez n, gerard d. br j dermatol. 2015; 172(suppl 1):52–58. 4. lasek rj, chren mm. arch dermatol. 1998; 134: 454-8. 5. gieler u et al. jeadv. 2015; 29 (suppl. 4):12–14. 6. moore a, green lj, bruce s, et al. j drugs dermatol. 2018 sep 1;17(9):987-996. 7. hudgens s, harper jc, daniels sr, et al. j drugs dermatol. 2015; 14(6):552-9. sponsored by almirall, s.a. references emmy graber,1 hilary baldwin,2 julie c. harper,3 linda stein gold,4 ayman grada,5 andrew f. alexis,6 adelaide hebert,7 richard g. fried,8 evan a rieder,9 james del rosso,10 siva narayanan,11 volker koscielny,12 ismail kasujee, 12 leon kircik13 1the dermatology institute of boston and northeastern university, boston, ma; 2acne treatment and research center, brooklyn, ny; 3the dermatology and skin care center of birmingham, birmingham, al; 4henry ford health system, bloomfield, mi; 5department of dermatology, case western reserve university school of medicine, cleveland, oh; 6weill cornell medical college, new york, ny; 7uthealth mcgovern medical school, houston, tx; 8yardley dermatology associates, morrisville, pa; 9new york university grossman school of medicine, new york, ny; 10jdr dermatology research/thomas dermatology, las vegas, nv; 11avant health llc, bethesda, md; 12almirall sa, barcelona, spain; 13icahn school of medicine, mount sinai, new york, ny. patient reported outcomes and investigator global assessment of acne vulgaris among patients with moderate to severe non-nodular acne vulgaris administered sarecycline in real-world community practices across the u.s. (proses study) presented at fall clinical dermatology conference, 2022 – october 19-23, 2022 – las vegas, nv • acne vulgaris, hereinafter referred to as acne, affects up to 50 million americans and is the most common skin condition in the united states (u.s).1 • acne has been shown to negatively affect qol; resulting in low selfesteem and increased social and emotional anxiety.2,3 • patients with acne report more effects of their skin condition on their functioning, emotions, and symptoms than do patients with isolated benign skin lesions or those in the normative sample.4 • acne has also been associated with considerable negative psychosocial impact, causing significant negative effects on self-image.5 • sarecycline is a newer oral tetracycline class of narrow spectrum antibiotic, a first line therapy treatment for moderate to severe acne patients. sarecycline is a viable option for acne patients to reduce disease burden, due to its safety profile and efficacy demonstrated in two identical phase-iii randomized, controlled trials.6 • assessing patient reported outcomes (pros) and clinical effectiveness (in terms of investigator global assessment (iga) of acne) among patients in real-world setting is important to inform hcps and payers to aid their clinical and reimbursement decisions, respectively. background conclusions • patients with moderate to severe acne using sarecycline reported a statistically significant improvement in acne symptoms, and social/emotional impact, as measured by validated asis questionnaire. • majority of acne patients had significant reduction in acne severity, and majority (58.9%) had iga success at week-12. • overwhelming majority of physicians (88.1%) were satisfied/very satisfied with sarecycline outcomes. • assessing the impact of sarecycline treatment on acne patient outcomes, including patient qol, in real-world community practice settings highlights the humanistic and clinical benefits associated this narrow-spectrum antibiotic treatment option. methods • single-arm, prospective cohort study (proses) was conducted with moderate to severe non-nodular acne patients >9 years who were prescribed sarecycline in real-world community practices in the us. • a total of 300 subjects were enrolled from 30 community practices across the u.s. • primary outcome measures included validated acne symptom and impact scale (asis) questionnaire responses (from subjects (>12 years) and caregivers (for subjects 9-11 years) at week-12 and corresponding change from baseline (cfb). • asis is a 17-item validated instrument that asks patients about the signs and impact of acne on emotional and social wellbeing and is a viable tool to assess disease burden and treatment outcomes.7 • asis contains signs domain (items 1-9) and impact domain (emotional (items 10-15) & social (items 16-17)); all items are scored on a five-point adjectival response scale (score 0-4); higher scores indicate severe symptoms or negative impact of acne. • secondary outcome measure was physician-reported facial iga collected on a five-point adjectival response scale (score 0 (clear) 4 (severe)). iga success was assessed as >2-grade improvement in iga and a score 0 [clear] or 1 [almost clear] at week-12. • last observation carried forward (locf) imputation was considered for imputing missing data for the calculation of iga success: however, there was no missing data at week-12, within the analytic population. • physician satisfaction with sarecycline outcome at individual patientlevel was also assessed at week-12. objective • to evaluate pros in terms of self-perceived acne signs and impact of acne on emotional/social functioning, and evaluate iga success at week12, among acne patients administered sarecycline, in community practices across the u.s. results • a total of 253 acne patients completed the study. • pediatric (9-17 years): 39.92%; adults (>18 years): 60.08%. • male: 33.60%; female: 66.40%. • white: 68.39%; african-american: 9.88%; asian: 7.11%. • a statistically significant increase in patients with clear or almost clear acne at week-12 (baseline: 0%, week-12: 58.90%; p<0.0001). correspondingly, iga success was observed in majority (58.90%) of acne patients at week-12. • a statistically significant reduction in patients with moderate/severe acne at week-12 (baseline: 100%, week-12: 11.10%; p<0.0001). resultsresults n=253 for all items. in comparison to baseline: *p<0.0001; ^p<0.0001; **p=0.0006; ***p=0.0001; ^^ p=0.0101. asis signs domain 44.3% 36.0% 19.8% 64.8%* 26.1% 9.1%** 0.0% 100.0% not at all/a little somewhat quite a bit/very much p ro po rti on o f p at ie nt s baseline 12 weeks a1: how oily is your face right now? 13.0% 34.4% 52.6% 63.6%* 22.1% 14.2%^ 0.0% 100.0% none/a few some quite a bit/a lot p ro po rti on o f p at ie nt s baseline 12 weeks a2: how many pimples do you have on your face right now? 34.8% 26.5% 38.7% 57.7%* 21.0% 21.3%^ 0.0% 100.0% none/a few some quite a bit/a lot p ro po rti on o f p at ie nt s baseline 12 weeks a3: how many acne scars (holes or indents) do you have on your face right now? 62.5% 21.3% 16.2% 83.0%* 11.5% *** 5.5% 0.0% 100.0% none/a few some quite a bit/ a lot p ro po rti on o f p at ie nt s baseline 12 weeks a4: how many scabs from acne do you have on your face right now? 43.9% 25.3% 30.8% 66.8%* 18.2% 15.0%^ 0.0% 100.0% none/ a few some quite a bit/a lot p ro po rti on o f p at ie nt s baseline 12 weeks a5: how many dark marks from acne do you have on your face right now? 38.3% 29.3% 32.4% 73.1%* 17.0% 9.9%^ 0.0% 100.0% none/ a few some quite a bit/ a lot p ro po rti on o f p at ie nt s baseline 12 weeks a6: how many blackheads do you have on your face right now? 53.8% 26.9% 19.4% 85.4%* 10.3% 4.4%^ 0.0% 100.0% none/a few some quite a bit/ a lot p ro po rti on o f p at ie nt s baseline 12 weeks a7: how many whiteheads do you have on your face right now? 31.2% 34.0% 34.8% 63.6%* 22.5% 13.8%^ 0.0% 100.0% none/a few some quite a bit/ a lot p ro po rti on o f p at ie nt s baseline 12 weeks a8: how much redness do you have on your face right now? 4.7% 20.6% 74.7% 59.3%* 28.1% 12.7%^ 0.0% 100.0% clear/ almost clear mild moderate/ severe p ro po rti on o f p at ie nt s baseline 12 weeks a9: overall, how is the acne on your face right now? 2.4% 11.5% 86.2% 37.2%* 34.8% 28.1%^ 0.0% 100.0% excellent/ very good good fair/bad p ro po rti on o f p at ie nt s baseline 12 weeks a10: over the past 7 days, rate how your face looked because of your acne? 31.2% 34.0% 34.8% 70.8%* 24.5% 4.7%^ 0.0% 100.0% never/ rarely some of the time most/ all of the time p ro po rti on o f p at ie nt s baseline 12 weeks a11: over the past 7 days, how often did you feel sad because of the acne on your face? 28.9% 32.4% 38.7% 71.2%* 20.2% 8.7%^ 0.0% 100.0% never/ rarely some of the time most/ all of the time p ro po rti on o f p at ie nt s baseline 12 weeks a12: over the past 7 days, how often did you feel embarrassed because of the acne on your face? 23.3% 30.0% 46.6% 68.0%* 20.6% 11.5%^ 0.0% 100.0% never/ rarely some of the time most/ all of the time p ro po rti on o f p at ie nt s baseline 12 weeks a13: over the past 7 days, how often did you feel selfconscious because of the acne on your face? 12.7% 25.7% 61.7% 51.4%* 31.2% 17.4%^ 0.0% 100.0% never/ rarely some of the time most/ all of the time p ro po rti on o f p at ie nt s baseline 12 weeks a14: over the past 7 days, how often did you annoyed because of the acne on your face? 30.0% 30.4% 39.5% 65.6%* 23.7% 10.7%^ 0.0% 100.0% never/ rarely some of the time most/ all of the time p ro po rti on o f p at ie nt s baseline 12 weeks a15: over the past 7 days, how often did you feel not confident because of the acne on your face? 64.4% 18.6% 17.0% 89.3%* 7.1% 3.6%^ 0.0% 100.0% never/ rarely some of the time most/ all of the time p ro po rti on o f p at ie nt s baseline 12 weeks a16: over the past 7 days, how often did you choose not to be around other people? 77.5% 16.6% 5.9% 93.7%* 4.7% 1.6%^^ 0.0% 100.0% never/ rarely some of the time most/ all of the time p ro po rti on o f p at ie nt s baseline 12 weeks a17: over the past 7 days, how often did someone make bad comments about the acne on your face? asis impact domain: emotional impact subscale asis impact domain: social impact subscale 2.0 2.1 2.4 1.0 1.2 1.1 1.3 0.4 0.0 1.0 2.0 3.0 4.0 signs impact emotional subscale (impact) social subscale (impact) m ea n a s is s co re baseline week 12 n= 253. impact domain includes emotional and social impact subscales. cfb: change from baseline to week-12. *p <0.0001 mean asis scores significantly decreased over the 12-week sarecycline treatment period cfb: 0.77* cfb: 1.01* cfb: 1.15* cfb: 0.60* 88.10% 6.70% 3.10% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% very satisfied/satisfied neutral dissatisfied/very dissatisfied n=253. for majority of acne patients, physicians were very satisfied or satisfied with sarecycline treatment outcomes at week-12 p ro po rti on o f p at ie nt s acne severity (by iga) decreased significantly over the 12-week sarecycline treatment period 0.00% 100.00% 58.90%* 11.10%* 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% iga 0 or 1 iga 3 or 4 baseline week 12 p ro po rti on o f p at ie nt s n=253. *p<0.0001. patient’s individual acne signs and social/emotional impact significantly improved over the 12-week sarecycline treatment period survey methodology • baseline and primary endpoint (month 4) images from harmonytm were pooled (84 subjects) ─ of the 93 harmonytm subjects who completed pan-facial treatment, 9 subjects were excluded from this analysis due to inconsistencies unrelated to treatment between the before and after images (e.g. presence of makeup, lipstick, or changes in hair color). • an online task was developed to understand how a representative sample of the us population perceives the harmonytm subjects based on their facial appearance ─ combined total of 2000 male and female respondents across the us • task probed each respondent on key traits associated with impressions (e.g. attractive, successful, healthy, approachable) • the study included two respondent groups: ─ group 1 (n=1500): viewed randomly selected single photographs of different harmonytm subjects (3 before, 3 after) ─ group 2 (n=500): viewed 6 unique pairs of matched before/after photographs in random order • all respondents were also asked questions evaluating importance of facial appearance, attractiveness, and personal views of facial aesthetic treatments in society pan-facial treatment positively and significantly impacts social perception steven dayan, md1; alexander rivkin, md2; jonathan m. sykes, md3; craig f. teller, md, faad4; susan h. weinkle, md5; garrett t. shumate, bs6; conor j. gallagher, phd6 1denova research, chicago, il, usa; 2david geffen school of medicine, university of california at los angeles, los angeles, ca, usa; 3uc davis medical group, sacramento, ca, usa; 4bellaire dermatology associates, bellaire, tx, usa; 5university of south florida, bradenton, fl, usa; 6allergan plc, irvine, ca • harmonytm is the first clinical trial to examine the impact of a unique combination of multiple, non-invasive facial treatments using a range of validated measures ─ results from harmonytm extended beyond physical improvement by demonstrating increased subject satisfaction and psychosocial benefits • self-assessments and societal assessments are made based on the entire face and not just one feature. there is an increasing trend for a pan-facial approach to facial rejuvenation • despite this trend, no studies have evaluated the impact of pan-facial aesthetic treatment on social perception • objective: to evaluate how the social perception of each harmonytm subject is impacted following pan-facial treatment background • pan-facial treatment positively and significantly impacted how harmonytm subjects were perceived by society ─ subjects were perceived as being more socially adept, successful at attracting others, attractive, friendly, successful, healthy, approachable, educated, financially successful, hirable and younger • respondents believe that attractiveness is important and facial aesthetic treatments are socially acceptable conclusions group 2: paired images • respondents preferred the after treatment photo for all positive traits trait x % of subjects were considered more (trait) following pan-facial treatment attractive 80 % someone with good social skills 80 % intelligent 76 % successful 75 % kind 74 % healthy 74 % trustworthy 73 % friendly 69 % approachable 69 % likeable 68 % someone who has social anxiety 29 % legend: positive attributes negative attributes • respondents perceived after treatment photo as more successful at attracting others, hirable, educated, financially successful, and younger question x % of subjects in which the after treatment photo was preferred who is more successful at attracting others? 77 % who would you hire? 73 % who is more financially successful? 74 % who has a higher level of education? 74 % who is older? 20% (after image: mean 4.85 years younger) results • subjects were perceived as significantly more socially adept, successful at attracting others, attractive, friendly, successful, healthy, approachable, and younger trait mean change (before to after) *statistically significant difference (p<0.05) someone who has social anxiety -0.29* success at attracting others 0.22* attractive 0.15* someone with good social skills 0.13* friendly 0.12* successful 0.12* healthy 0.10* approachable 0.09* age -1.21 yrs* likeable 0.02 intelligent -0.02 trustworthy -0.02 kind -0.01 group 1: single image responder demographics 2000 respondents age (mean) 41.1 male 49% female 51% heterosexual 87% student / retired 13% not employed 11% hispanic 17% white 66% black/aa 13% group 1 & 2: respondent beliefs about attractiveness • respondents believe that attractiveness is important and facial aesthetic treatments are socially acceptable low 1 level of agreement society places emphasis on physical appearance 6.8 5.9 5.5 5.2 5.1 4.8 4.1 4.1 how important is physical attractiveness in social interactions? facial aesthetic treatments are a socially acceptable way to... physical attractiveness affects success professionally i would never consider facial aesthetic treatments physical attractiveness becomes less important as men age only vain people get facial aesthetic treatments physical attractiveness becomes less important as women age high 8 what age is a woman old? 56.4 what age is a man old? 58.8 materials and methods the person in this image is*… which of the two images do you think looks more*... *additional questions asked about the subject’s age, success at attracting others, education level, income level, and hireability (please select one response per row.) completely disagree 1 2 3 4 5 6 7 completely agree 8 kind healthy someone who has social anxiety approachable attractive someone with good social skills trustworthy intelligent friendly likeable successful completely disagree 1 2 3 4 5 6 7 completely agree 8 kind someone who has social anxiety approachable attractive healthy intelligent successful likeable someone with good social skills friendly trustworthy screening group 1: single image group 2: paired images fall clinical dermatology conference, las vegas, october 12-15, 2017 acknowledgments: this study was funded by allergan plc. medical writing and editorial assistance was provided to the authors by cactus communications, and was funded by allergan plc. all authors met the icmje authorship criteria. neither honoraria nor other form of payments were made for authorship. financial disclosures: s dayan received research support, speaking fees, or consulting fees from allergan plc, galderma, merz, and valeant. a rivkin serves as a consultant and investigator for allergan plc and merz aesthetics, usa. jm sykes, cf teller, and sh weinkle have no conflicts to disclose. gt shumate and cj gallagher are employees of allergan plc and may own stock or stock options in the company. • subjects were perceived as earning more under 50k 62% under 50k 58% before (b) after (a) 50k and above 42% 50k and above 38% 4% 3% 11% 28% 39% 19% 9% 25% 41% 21% a perceived income level $100,000 or more $75,000$99,000 $50,000$74,999 $25,000$49,999 less than $25,000 • subjects were more likely to be perceived as college educated 43% before (b) after (a) 47% 5% 6% 22% 19% 25% 28% 18% 20% 25% 32% perceived educational level graduate degree college associate degree some college but no degree completed high school or less • subjects were more likely to be perceived as having a higher occupational status perceived occupational level manual or service worker 40% managerial 20% managerial 27% manual or service worker 34% before (b) after (a) senior level managerial, admin, or professional junior managerial, admin, or professional clerical worker skilled manual or service worker semi-skilled manual or service worker manual or service worker other retired unemployed 13% 16% 13% 6% 6% 6% 7% 11% 14% 17% 17% 10% 17% 12% 9% 9% 8% 8% a scan to obtain pdf of poster to obtain a pdf of this poster: scan the qr code or visit www.allergancongressposters.com/859100 charges may apply. no personal information is stored. enter a valid e-mail to send this qr code or click to download. please ensure that qrcode@allergancongressposters.com has been added to your safe senders list or spam filter. fc17posterallergandayanpanfacialtxsocialperception.pdf skin september 2017 volume 1 issue 2 copyright 2017 the national society for cutaneous medicine 86 brief articles positive nikolsky sign and pinpoint “lakes of pus” christina y. wong md a , steven d billings md b , christine b warren md a a cleveland clinic foundation, department of dermatology, cleveland, oh b cleveland clinic foundation, department of dermatopathology, cleveland, oh a 54-year-old man with a past medical history of paraplegia, osteomyelitis, sacral decubitus ulcer, suprapubic catheter, and several reported drug eruptions was seen for evaluation of skin sloughing without any tenderness to palpation. he reports being on chronic oral antibiotics including amoxicillin/clavulanic acid and ciprofloxacin over the past two years for osteomyelitis. two days prior to evaluation, he had been hospitalized for osteomyelitis of the left iliac bone and was treated with intravenous vancomycin and meropenem. he notes that when he was started on vancomycin, he developed red man syndrome and had a similar rash in the past to vancomycin which resolved with slower infusion. he also reported the development of a rash to other antibiotics including ampicillin, gentamicin, and sulbactam sodium. he denied having mucosal involvement, skin sloughing, or a abstract a 54-year-old man with a past medical history of paraplegia, osteomyelitis, sacral decubitus ulcer, suprapubic catheter, and several reported drug eruptions was seen for evaluation of skin sloughing without any tenderness to palpation. he reported being on chronic oral antibiotics including amoxicillin/clavulanic acid and ciprofloxacin over the past two years for osteomyelitis. two days prior to evaluation, he had been hospitalized for osteomyelitis of the left iliac bone and was treated with intravenous vancomycin and meropenem. initial evaluation revealed widespread nikolsky sign with extensive involvement of the back, abdomen, and extremities without any tenderness. involving 30-40% body surface area were scattered deep red macules and patches. the histopathologic findings were consistent with the diagnosis of acute generalized exanthematous pustulosis (agep). clinically, agep appears as diffuse erythema with several small, non-follicular pustules and possible peripheral neutrophilia or eosinophilia. a positive nikolsky sign can be seen with agep, but it is not specific, and has been referred to as a ‘pseudo-nikolsky sign.’ systemic involvement, such as renal insufficiency, has been reported in agep. there are few reports in the literature describing agep with ten-like features. we present an interesting patient with agep and ten-like features who improved after cessation of vancomycin and meropenem and a short course of systemic steroids. case report skin september 2017 volume 1 issue 2 copyright 2017 the national society for cutaneous medicine 87 diagnosis of stevens-johnson syndrome with any medications in the past. initial evaluation revealed widespread nikolsky sign with extensive involvement of the back, abdomen, and extremities without any tenderness. involving 30-40% body surface area were scattered deep red macules and patches [figure 1]. focal areas of the arms and abdomen revealed several pinpoint pustules coalescing into “lakes of pus” [figure 2]. examination of the mouth revealed a non-tender, beefy red tongue. the oral mucosa, nasal mucosa, ocular mucosa, and genital mucosa were uninvolved. no purpuric, dusky, atypical targetoid lesions or hemorrhagic crusts were appreciated. a punch biopsy was performed for frozen section [figure 3_100x] and hematoxylin and eosin staining [figure 4_100x]. he was normotensive and afebrile. laboratory evaluation showed a significant leukocytosis of 69.00 k/mm 3 (3.70-11.0 k/ul normal range) with a differential significant for 97.0% neutrophils and an absolute neutrophilic count of 66.93 k/ul (1.45-7.50 k/ul normal range). the differential further included 1.0% lymphocytes with an absolute lymphocyte count of 0.69 k/ul (1.00-4.00 k/ul normal range), monocytes 2.0% and absolute monocyte count of 1.38 k/ul (0.000.86 k/ul), and no detectable eosinophils or basophilic cells. creatinine 1.24 mg/dl (0.70 1.40 mg/dl), alkaline phosphatase 92 u/l (40 150 u/l), ast 18 u/l (7 40 u/l), and alt 8 u/l (5 50 u/l) were all within normal limits. of note, the patient’s baseline creatinine was 0.78 mg/dl. frozen section [figure 3_100x] reveals desquamating basket weave orthokeratosis with intraepidermal bullous formation of the superficial epidermis. the remainder of the epidermis is mildly spongiotic. within the dermis, there is mixed and acute chronic inflammatory infiltrate. a gms and gram stain fail to highlight fungal hyphae and bacterial organisms. the histopathologic findings are consistent with the diagnosis of acute generalized exanthematous pustulosis. permanent section by hematoxylin and eosin stain [figure 4_100x] demonstrates an epidermis with mild spongiosis and scattered neutrophils within the stratum corneum. within the superficial dermis, there is diffuse papillary dermal edema with numerous neutrophils. the histologic differential diagnosis is consistent with acute generalized exanthematous pustulosis. infectious disease was consulted by the primary team and recommended stopping all antibiotics. due to the progression of skin lesions after drug cessation, the patient was treated with 1.4 mg/kg/day (80mg bid) of methylprednisolone with marked improvement of skin lesions. by day three of treatment, the patient had a negative nikolsky sign and no new pustules were appreciated. his creatinine decreased to 0.92 with steroid treatment. he was tapered off prednisone within a week and continued to re-epithelialize. skin september 2017 volume 1 issue 2 copyright 2017 the national society for cutaneous medicine 88 figures figure 1: 30-40% body surface area with deep red macules and patches and widespread nikolsky sign figure 2: focal areas of the arms and abdomen with several pinpoint pustules coalescing into “lakes of pus” figure 3: 100x frozen section reveals desquamating basket weave orthokeratosis with intraepidermal bullous formation of the superficial epidermis figure 4: 100x hematoxylin and eosin stain demonstrates epidermis with mild spongiosis and scattered neutrophils within the stratum corneum skin september 2017 volume 1 issue 2 copyright 2017 the national society for cutaneous medicine 89 acute generalized exanthematous pustulosis (agep) is considered one of the severe forms of a cutaneous adverse drug reaction. clinically, agep appears as diffuse erythema with several small, nonfollicular pustules and possible peripheral neutrophilia or eosinophilia. it has been associated with up to a 2% mortality rate 1 compared to ten which is associated with a 25-30% mortality rate. 2 leukocytosis is typically seen at an elevated neutrophil count above 7.5 × 10 9 /l. 2 classically, skin lesions develop between 24-48 hours after exposure to the offending drug or infectious agent. 4 both meropenem and vancomycin have been described in the literature as inciting agents of agep. 5,6 systemic involvement, such as renal insufficiency, has been reported in agep. 7 a positive nikolksy sign can be seen with agep, but is not specific, and has been referred to as a ‘pseudo-nikolsky sign.’ 8 our patient presented with a clinical picture that resembled an overlap between agep and toxic epidermal necrolysis (ten). there are reports in the literature describing agep with ten-like features. van hattem and kardaun presented a case of agep with ten-like features due to flucloxacillin with the patient developing similar superficial erosions of erythematous areas, studded with pustules. 8 they further reviewed the literature describing ten additional cases describing ten-like features clinically with agep diagnosed on histopathology. bouvresse et al. reviewed 216 cases with histologically data confirming discharge diagnoses and described an overlap of agep and sjs in 21% of those patients assessed. 8 histopathology aids in distinguishing these two entities. ten will present as an interface dermatitis with full-thickness necrosis of the epidermis and a mild perivascular lymphocytic infiltrate and dyskeratotic keratinocytes. 10 in contrast, agep reveals spongiform features with subcorneal or intraepidermal pustules, neutrophils, and eosinophils. we present a patient with agep and ten-like features who improved after cessation of vancomycin and meropenem and a short course of systemic steroids. conflict of interest disclosures: none. funding: none. corresponding author: christina y. wong, md cleveland clinic foundation department of dermatology 9500 euclid ave a61 cleveland, oh 44118 216-444-4480 wongc3@ccf.org references: 1. martins a, lopes lc, paiva lopes mj, et al. acute generalized exanthematous pustulosis induced by hydroxychloroquine. eur j dermatol. 2006;16:317-318. 2. harr t, french le. toxic epidermal necrolysis and stevens-johnson syndrome. orphanet j rare dis. 2010;5:39. 3. szatkowski j, schwartz ra. acute generalized exanthematous pustulosis (agep): a review and update. j am acad dermatol. 2015;73(5):843-8. 4. sidoroff a, dunant a, viboud c, et al. risk factors for acute generalized exanthematous pustulosis (agep)-results of a multinational case-control study (euroscar). br j dermatol. 2007;157(5):989-96. 5. khalel mh, fattah saleh sa, f el-gamal ah, najem n. acute generalized exanthematous discussion skin september 2017 volume 1 issue 2 copyright 2017 the national society for cutaneous medicine 90 pustulosis: an unusual side effect of meropenem. indian j dermatol. 2010;55(2):176-7. 6. mawri s, jain t, shah j, hurst g, swiderek j. vancomycin-induced acute generalized exanthematous pustulosis (agep) masquerading septic shock-an unusual presentation of a rare disease. j intensive care. 2015;3:47. 7. hotz c, valeyrie-allanore l, haddad c, et al. systemic involvement of acute generalized exanthematous pustulosis: a retrospective study on 58 patients. br j dermatol. 2013;169(6):122332. 8. van hattem s, beerthuizen gi, kardaun sh. severe flucloxacillin-induced acute generalized exanthematous pustulosis (agep), with toxic epidermal necrolysis (ten)-like features: does overlap between agep and ten exist? clinical report and review of the literature. br j dermatol. 2014;171(6):1539-45. 9. bouvresse s, valeyrie-allanore l, ortonne n, et al. toxic epidermal necrolysis, dress, agep: do overlap cases exist?. orphanet j rare dis. 2012;7:72. 10. iwai s, sueki h, watanabe h, sasaki y, suzuki t, iijima m. distinguishing between erythema multiforme major and stevens-johnson syndrome/toxic epidermal necrolysis immunopathologically. j dermatol. 2012;39(9):781-6. 11. halevy s, kardaun sh, davidovici b, wechsler j. the spectrum of histopathological features in acute generalized exanthematous pustulosis: a study of 102 cases. br j dermatol. 2010;163(6):1245-52. skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 911 brief article malignant angiosarcoma masquerading as benign epithelioid hemangioma karishma daftary, ba1, joaquin brieva, md1, raj chovatiya, md, phd1 1 department of dermatology, feinberg school of medicine at northwestern university, chicago, il a previously healthy 67-year-old female presented to dermatology clinic with rapidly growing, non-painful, non-tender, dark red nodules on the scalp (figure 1). three months prior she had noted a single, similar red nodule that was excised and diagnosed as a benign epithelioid hemangioma. a punch biopsy of a newer lesion on the scalp was performed. the epidermis was unremarkable, and the dermis showed multinodular proliferation of immature vessels in myxoid stroma lined by epithelioid and spindled endothelial cells with increased cellularity, mitoses, and vacuolization (figure 2 and 3). occasional eosinophils and lymphocytes were noted. immunohistochemistry was positive for factor viii, cd34, erg, and sma. frank atypia was not identified. these findings suggested a benign vascular neoplasm consistent with epithelioid hemangioma (eh). figure 1. rapidly growing, non-painful, nontender, dark red scalp papulonodules on the scalp with central necrotic, vascular plaque. abstract in this report, we describe a case of a healthy 67-year-old female with rapidly growing red nodules on the scalp that demonstrated histological features of benign epithelioid hemangioma on multiple instances yet behaved clinically as a malignant angiosarcoma. despite multiple rounds of resection, radiation, and chemotherapy, the patient ultimately succumbed from her widely metastatic disease. diagnosis of vascular neoplasms, including the spectrum of low-grade epithelioid hemangioma, intermediate-grade epithelioid hemangioendothelioma, and high-grade angiosarcoma remains challenging due to overlapping clinical and histopathological features. this report is presented to highlight the need for clinicians to interpret histopathology, whether benign or malignant, in the context of clinical observation as the clinical course may not always match the biopsy. case report skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 912 figure 2. punch biopsy of a scalp lesion demonstrating a multinodular proliferation of immature vessels in myxoid stroma lined by epithelioid and spindled endothelial cells with increased cellularity, mitoses, and vacuolization (hematoxylin & eosin) at 10x figure 3. h&e biopsy at 40x skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 913 prior to planned curative excision and over the course of the following month, the lesions showed explosive growth, spreading across the scalp with satellite nodules. during this time the patient also developed headaches and palpable lymphadenopathy. imaging with pet-ct revealed an infiltrating 1.5cm x 2.1cm x 1.3cm tumor with calvarium invasion, metastatic lymphadenopathy, and innumerable soft tissue masses. lymph node fine needle aspiration mirrored skin histopathology, which itself had been independently evaluated as eh at four separate academic centers. clinically, despite benign pathology, these findings were more consistent with an aggressive angiosarcoma. the patient had treatments of radiation, paclitaxel, doxorubicin, and docetaxel/gemcitabine over the next several months, but she unfortunately continued to show progression of disease and ultimately succumbed to her illness. epithelioid hemangioma (eh), also known as angiolymphoid hyperplasia with eosinophilia, is a benign, slow-growing, dermal vascular proliferation presenting with red-brown, dome-shaped papulonodules. first described in 1969 by wells and whimster, the lesions typically appear on the head and neck and more rarely, on the trunk, extremities, and genitalia.1,2 the disease commonly presents in the third or fourth decade of life and may have a slight predilection towards females.1 patients with eh are often asymptomatic, but some experience pain, pulsations, pruritus, or bleeding due to the vascular nature of the lesions.1,2 histologically, eh is characterized by aggregates of enlarged blood vessels lined with plump endothelial cells and surrounded by lymphocytes and eosinophils.1 diagnosis of eh can be quite challenging, given similarities to other vascular tumors. eh is at the low-grade end of a spectrum occupied by the intermediategrade malignant epithelioid hemangioendothelioma (ehe) and the highgrade angiosarcoma. per the classification system set forth by the international society for the study of vascular anomalies (issva) that categorizes vascular tumors as benign, locally aggressive/borderline, or malignant, eh is designated as a benign whereas both ehe and angiosarcoma are categorized as malignant tumors.3 ehe is a rare malignant tumor with an epithelioid or histiocytoid appearance developing from vascular endothelial or preendothelial cells. similar to eh, the disease presents in middle age, with a median age of onset of 36, and has a slight predilection for females.4 50-76% of patients with this vascular tumor are asymptomatic and diagnosed incidentally on imaging.4 when symptomatic, ehe has a broad range of clinical presentations that can affect numerous sites, including most commonly the lung and/or bone, which can present as pleuritic chest pain, pleural effusion, hemoptysis, bone pain, and fracture.4 histological features of ehe include vacuolated endothelial cells growing in nests and cords.1,5 identification of intranuclear inclusions, intracytoplasmic vacuoles, stromal changes, and few mitotic figures may be helpful in differentiating from epithelioid angiosarcoma.5,6 on the high-grade spectrum of vascular tumors is angiosarcoma. there are multiple variants of cutaneous angiosarcoma including angiosarcoma of the head and neck, angiosarcoma associated with lymphedema, radiation-induced angiosarcoma, and epithelioid angiosarcoma.7 they differ clinically from eh discussion skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 914 and ehe in that they often present in the elderly and the lesions spread rapidly in a centrifugal pattern.5 while eh has a benign clinical course, angiosarcoma is a highly aggressive, metastatic, endothelial malignancy with high mortality. angiosarcoma may mimic eh histologically with certain similar features including vascular channels lined by endothelial cells and a lymphoid infiltrate.5 angiosarcoma is differentiated by increased mitotic activity, necrosis, hemorrhage, irregular vascular channels dissecting through dermis, and an absence of eosinophilic infiltrate.5,7 prognosis of angiosarcoma is poor; a recent meta-analysis found the mean 5-year survival rate to be 33.35%.8 poor prognostic factors include greater than 70 years of age, tumor size larger than 5cm, and involvement of the head and neck. the standard treatment for angiosarcoma is surgical resection, but this is not always an option in patients with unresectable and/or metastatic disease.9 systemic therapy with paclitaxel is considered to be first-line for advanced cutaneous angiosarcoma.9,10 second-line treatment options include pazopanib, eribulin mesylate, and trabectedin.9 there are few examples in the literature demonstrating difficulty in distinguishing between these vascular neoplasms based on pathology alone. marcum et al. reported a patient who had numerous, rapidlyproliferating, violaceous nodules located on the scalp with pathologic features of eh despite certain clinical features of angiosarcoma.5 the patient’s lesions showed complete clinical resolution with long-pulsed dye laser therapy and shave excision – standard treatment modalities for patients with eh. conversely, zeitouni et al. reported a patient with scalp nodules that showed benign clinical features of eh even though histopathology demonstrated findings consistent with angiosarcoma.11 the patient’s lesions were surgically excised with no recurrence. to our knowledge, an aggressive vascular entity with pathologic features of eh and clinical features of refractory angiosarcoma has not been previously reported. this case serves as a reminder that whether benign or malignant, clinicians should always interpret histopathology in the context of clinical observation. clinicopathologic correlation and differential diagnosis are especially critical for vascular neoplasms where histopathology may be challenging, as with the spectrum of eh, ehe, and angiosarcoma. conflict of interest disclosures: raj chovatiya has served as an advisory board member, consultant, speaker, and/or investigator for abbvie, apogee, arcutis, argenx, aslan, beiersdorf, boehringer ingelheim, bristol myers squibb, cara therapeutics, dermavant, eli lilly and company, galderma, genentech, incyte, leo pharma, l’oréal, novan, inc., pfizer inc., regeneron, sanofi, and ucb. karishma daftary and joaquin brieva have no conflicts to disclose. funding: none corresponding author: raj chovatiya, md, phd department of dermatology northwestern university feinberg school of medicine 676 n st clair st suite 1600 chicago, il 60611 email: raj.chovatiya@gmail.com references: 1. guo r, gavino ac. angiolymphoid hyperplasia with eosinophilia. arch pathol lab med. may 2015;139(5):683-6. doi:10.5858/arpa.2013-0334-rs 2. adler bl, krausz ae, minuti a, silverberg ji, lev-tov h. epidemiology and treatment of angiolymphoid hyperplasia with eosinophilia conclusion skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 915 (alhe): a systematic review. j am acad dermatol. mar 2016;74(3):506-12.e11. doi:10.1016/j.jaad.2015.10.011 3. saleh js, whittington cp, bresler sc, patel rm. cutaneous vascular tumors: an updated review. hum pathol. apr 12 2023;doi:10.1016/j.humpath.2023.04.004 4. sardaro a, bardoscia l, petruzzelli mf, portaluri m. epithelioid hemangioendothelioma: an overview and update on a rare vascular tumor. oncol rev. sep 23 2014;8(2):259. doi:10.4081/oncol.2014.259 5. marcum cb, zager js, bélongie ip, messina jl, fenske na. profound proliferating angiolymphoid hyperplasia with eosinophilia of pregnancy mimicking angiosarcoma. cutis. sep 2011;88(3):122-8. 6. anderson t, zhang l, hameed m, rusch v, travis wd, antonescu cr. thoracic epithelioid malignant vascular tumors: a clinicopathologic study of 52 cases with emphasis on pathologic grading and molecular studies of wwtr1-camta1 fusions. am j surg pathol. jan 2015;39(1):132-9. doi:10.1097/pas.0000000000000346 7. requena l, sangueza op. cutaneous vascular proliferations. part iii. malignant neoplasms, other cutaneous neoplasms with significant vascular component, and disorders erroneously considered as vascular neoplasms. j am acad dermatol. feb 1998;38(2 pt 1):143-75; quiz 176-8. doi:10.1016/s0190-9622(98)70237-3 8. shin jy, roh sg, lee nh, yang km. predisposing factors for poor prognosis of angiosarcoma of the scalp and face: systematic review and meta-analysis. head neck. feb 2017;39(2):380-386. doi:10.1002/hed.24554 9. ishida y, otsuka a, kabashima k. cutaneous angiosarcoma: update on biology and latest treatment. curr opin oncol. mar 2018;30(2):107-112. doi:10.1097/cco.0000000000000427 10. penel n, bui bn, bay jo, et al. phase ii trial of weekly paclitaxel for unresectable angiosarcoma: the angiotax study. j clin oncol. nov 10 2008;26(32):5269-74. doi:10.1200/jco.2008.17.3146 11. zeitouni nc, hanna s, loree tr, brooks j, cheney rt. angiolymphoid hyperplasia with eosinophilia: a classic clinical presentation with histologic features of angiosarcoma. dermatol surg. aug 2002;28(8):772-5. doi:10.1046/j.1524-4725.2002.02006.x a phase iii, randomized, double-blind, controlled study (pemphix) to evaluate the efficacy and safety of rituximab versus mycophenolate mofetil in patients with pemphigus vulgaris victoria p. werth,1 pascal joly,2 daniel mimouni,3 emanual maverakis,4 patricia lehane,5 liudmila gearhart,6 pooneh pordeli,7 diana m. chen8 and the pemphix investigators 1perelman school of medicine, university of pennsylvania and corporal michael j. crescenz vamc, philadelphia, pa, usa; 2department of dermatology, rouen university hospital and inserm 1234, rouen, france; 3sackler school of medicine, tel aviv university, tel aviv, israel and rabin medical center, petah-tikva, israel; 4department of dermatology, university of california davis school of medicine, sacramento, ca, usa; 5roche products, ltd., welwyn garden city, uk; 6f. hoffmann la-roche, basel, switzerland; 7roche products, ltd., mississauga, on, canada; 8genentech, inc, south san francisco, ca, usa introduction • the aims of pemphigus vulgaris (pv) treatment are to control the disease, limit recurrence, and minimize side effects associated with treatment • systemic corticosteroids (cs) are first-line treatment1 • rituximab is an anti-cd20 monoclonal antibody approved to treat moderate to severe pv in the united states and europe2,3 – an independent analysis of the ritux 3 study4 demonstrated that at month 24, rituximab plus a short course of cs was significantly more effective than a standard dose and duration of cs in achieving complete remission off cs for ≥ 2 months (croff ≥ 2 months) in patients with pv5 • mycophenolate mofetil (mmf) is recommended in pemphigus treatment guidelines as a first-line cs-sparing agent and is commonly used, though its efficacy in pv has not been proven1,6 objective of the study • to compare the efficacy and safety of rituximab to mycophenolate mofetil in patients with moderate to severe pv methods figure 1. study design rituximab 1000 mg iv infusions (day 1, day 15, day 168 and day 182) + daily oral mmf-placebo rituximab-placebo iv infusions (day 1, day 15, day 168 and day 182) + daily oral mmf (1 g/day increased to 2 g/day in divided doses by week 2) 48-week safety follow-up screening (up to 28 days) • adults • confirmed pv diagnosis within the last 24 months • moderate-to-severely active pv (pdai activity score ≥ 15) • receiving 60-120 mg/day oral prednisone or equivalent (1.0-1.5 mg/kg/day) r an do m iz at io n* 1 :1 all patients: week 52 (primary endpoint)rituximab/placebo rituximab/placebo day 1, day 15 day 168, day 182 (completed) at day 1, 60 or 80 mg oral prednisone (or equivalent) with the aim of tapering to 0 mg/day by day 168 (week 24) *at randomization, patients were stratified by duration of pv and geographic region. cs, corticosteroid; mmf, mycophenolate mofetil; pdai, pemphigus disease area index; pv, pemphigus vulgaris. study endpoints • primary efficacy endpoint: at week 52, the proportion of patients achieving sustained complete remission (cr) without experiencing treatment failure – sustained cr was defined as pemphigus disease area index (pdai) activity score of 0 and 0 mg/day prednisone or equivalent for at least 16 consecutive weeks (i.e., sustained croff prednisone ≥ 16 weeks), during the 52-week treatment period • secondary efficacy endpoints (ranked): – cumulative oral cs dose (prednisone or equivalent) over the treatment period – total number of disease flares during the treatment period – time to sustained cr – time to disease flare – change in in health-related quality of life, as measured by the dermatology life quality index (dlqi) score, from baseline to week 52 • efficacy analyses were performed on the modified intent-to-treat (mitt) population, which excluded from the itt population exploratory data in 10 patients for whom telemedicine was used to enable accessibility for study participation • safety: adverse events (aes) and serious aes (saes), aes leading to study withdrawal, and cs-related aes – safety analyses were performed on the safety population (itt population) results patient enrollment • 135 patients were enrolled at 49 academic sites in 10 countries: united states, canada, argentina, brazil, france, germany, israel, italy, spain, & turkey – 52 (38.5%) from north america and 83 (61.5%) rest of world • at screening, 113 patients had moderate pv (pdai activity score 15-45) and 20 patients had severe pv (pdai activity score > 45)7; there were 2 patients with pdai activity score < 15 (major protocol deviation) patient disposition • 67 patients and 68 patients were randomized to rituximab and mmf, respectively. 66 patients (98.5%) in the rituximab arm and 58 (85.3%) in the mmf arm completed week 52 (figure 2) figure 2. patient disposition 1 patient (1.5%) withdrew from the study due to adverse event* 10 patients (14.7%) withdrew from the study due to: 3 (4.4%) adverse event* 1 (1.5%) lost to follow up 1 (1.5%) non-compliance with study drug 5 (7.4%) withdrawal by patient 135 patients randomized (itt population) rituximab n = 67 mmf n = 68 66 patients (98.5%) completed week 52 58 patients (85.3%) completed week 52 five patients treated via telemedicine were enrolled in each arm. *adverse events leading to withdrawal: lumbar vertebral fracture (1 rituximab patient); pneumonia, influenza, and pulmonary embolism (1 mmf patient), urinary retention (1 mmf patient), small cell lung cancer (1 mmf patient). itt, intent-to-treat; mmf, mycophenolate mofetil. demographics and baseline characteristics table 1. demographics and baseline characteristics mitt population rituximab (n = 62) mmf (n = 63) gender, n (%) male female 31 (50.0) 31 (50.0) 28 (44.4) 35 (55.6) age, years mean (sd) median (range) 50.2 (13.2) 50.0 (27-75) 46.9 (12.8) 46.0 (23-71) disease status*, n (%) newly diagnosed established 48 (77.4) 14 (22.6) 44 (69.8) 19 (30.2) pdai activity score (0-25)† screening mean (sd) baseline mean (sd) 31.7 (14.0) 24.9 (14.4) 30.3 (15.8) 23.4 (18.4) dlqi (0-30) mean (sd) 10.4 (8.1) 11.2 (8.9) *newly diagnosed = diagnosis of pv of < 6 months or no prior treatments for pv; established disease = pv for ≥ 6 months and received prior therapies for pv before study entry. †during the screening period (up to 28 days), the daily corticosteroid dose was tapered, as directed by the investigator on the basis of disease activity and tolerability to reach a dosage of 60 or 80 mg/day by day 1. therefore, pdai at screening/study entry may differ from pdai at baseline/day 1. dlqi, dermatology life quality index; mitt, modified intent-to-treat; mmf, mycophenolate mofetil; pdai, pemphigus disease area index. primary efficacy endpoint at week 52 • rituximab was superior to mmf, in combination with a tapering course of oral prednisone (or equivalent): – at week 52, a significantly higher proportion of patients in the rituximab arm achieved sustained croff prednisone ≥ 16 weeks than in the mmf arm (figure 3) figure 3. proportion of patients achieving sustained croff prednisone ≥ 16 weeks at week 52 40.3% (25 patients) 9.5% (6 patients) 0 10 20 30 40 50 rituximab (n = 62) mmf (n = 63) % p at ie nt s s us ta in ed c r of f difference: 30.8% (95% ci: 14.7% to 45.2%) p < 0.0001 cr, complete remission; mmf, mycophenolate mofetil. secondary efficacy endpoints corticosteroid exposure • patients in the rituximab arm had a significantly lower cumulative oral cs dose (prednisone or prednisone equivalent) over the 52-week treatment than in the mmf arm – the median (min, max) cumulative dose was 2775 mg (450, 22180) in the rituximab arm compared to 4005 mg (900, 19920) in the mmf arm (p = 0.0005) disease flare • total number of disease flares: significantly fewer number of flares occurred in patients treated with rituximab compared to mmf (6 vs. 44, p < 0.0001) (figure 4) • number of patients with disease flare: fewer rituximab-treated patients experienced ≥ 1 disease flare, 5 rituximab patients (8.1%) vs. 26 mmf patients (41.3%) figure 4. total number of disease flares 6 flares 44 flares 0 10 20 30 40 50 rituximab (n = 62) mmf (n = 63) to ta l n um be r of f la re s adjusted rate ratio: 0.12 (95% ci: 0.05 to 0.29); p < 0.0001 disease flare was defined as appearance of ≥ 3 new lesions a month that do not heal spontaneously within 1 week or by the extension of established lesions in a patient who has achieved disease control. mmf, mycophenolate mofetil. time to sustained croff ≥ 16 weeks • as less than 50% of patients had a sustained croff ≥ 16 weeks in both treatment arms, the median time to sustained cr was not estimable in either arm • the likelihood of achieving sustained cr on rituximab was ~5 times greater than on mmf (hazard ratio [hr] = 4.83 [95% ci, 1.97 to 11.81], p = 0.0003) time to first flare • as less than 50% of patients had a disease flare in both treatment arms, the median time to disease flare was not estimable in either arm • the likelihood of experiencing flare was significantly lower in the rituximab group than in the mmf group, i.e. the likelihood of a flare on rituximab was ~7 times lower than on mmf (hr = 0.15 [95% ci, 0.06 to 0.39], p < 0.0001) dermatology life quality index • significantly greater improvements in health-related quality of life from baseline at week 52 (as measured by the dlqi) were observed in patients treated with rituximab compared to mmf (figure 5) • in a post-hoc analysis, 61.7% of patients in the rituximab arm had achieved a dlqi score of 0 (no impairment in health-related quality of life) at week 52 compared to 25.0% of patients in the mmf arm figure 5. change in dlqi score from baseline at week 52 −8.87 −6.00 −10 −8 −6 −4 −2 0 2 e st im at ed m ea n c ha ng e fr om b as el in e, m m r m rituximab (n = 62) mmf (n = 63) im pr ov em en t difference: −2.87 (95% ci: −4.58 to −1.17), mmrm p = 0.0012 dlqi, dermatology life quality index; mmf, mycophenolate mofetil; mmrm, adjusted mixed models repeated measures. this study was funded by genentech, inc. support for third-party medical writing assistance, furnished by health interactions, inc., was provided by genentech, inc. presented at the winter clinical dermatology conference; january 17-20, 2020; kohala coast, hawaii safety table 2. adverse events rituximab (n = 62) mmf (n = 63) patients with ≥ 1 ae, n (%) 57 (85.1) 60 (88.2) total number of aes 352 301 patients with ≥ 1 sae, n (%) 15 (22.4) 10 (14.7) patients with ≥ 1 sae related to the study drug*, n (%) 6 (9.0) 5 (7.4) patients withdrawn from study due to ae, n (%) 1 (1.5) 3 (4.4) death, n (%) 0 1 (1.5)† patients with irr, n (%) 15 (22.4)‡ 6 (8.8)¶ patients with serious irr, n (%) 3 (4.5) 1 (1.5) patients with infection, n (%) 42 (62.7) 37 (54.4) patients with serious infection, n (%) 6 (9.0) 4 (5.9) total number of serious infections 8 6 patients with serious infection related to study drug*, n (%) 2 (3.0) 2 (2.9) total number of serious infections related to study drug 3 3 opportunistic infection**, n (%) 0 0 patients with grade 3 or higher cs-related aes*, n (%) 1 (1.5) 5 (7.4) total number of grade 3 or higher cs-related aes 1 6 *related as assessed by the investigator. †one patient in the mmf arm was diagnosed on day 107 and died on day 115 from small cell lung cancer related to the patient’s 50-year smoking history and unrelated to mmf. ‡the most common irr symptoms/preferred terms in the rituximab arm were dyspnoea (7.5%), erythema, hyperhidrosis, flushing/hot flush, hypotension and rash/rash pruritic (3.0% each). ¶irrs reported from placebo infusion. **pneumocystis jirovecii pneumonia prophylaxis was performed according to local clinical practice guidelines and investigator judgment. ae, adverse event; cs, corticosteroid; irr, infusion-related reaction; mmf, mycophenolate mofetil; sae, serious adverse event. adverse events and serious adverse events • the most common aes in ≥ 10% of rituximab-treated patients were irr (15 patients, 22.4%), headache (10 patients, 14.9%), lymphopenia (8 patients, 11.9%) and upper respiratory tract infection (7 patients, 10.4%) – the most common aes in ≥ 10% of mmf-treated patients were diarrhea (10 patients, 14.7%) and nasopharyngitis (8 patients, 11.8%) • saes related to rituximab were irr (3 patients), pneumonia and upper respiratory tract infection (1 patient), bursitis infective (1 patient) and abdominal pain (1 patient) – saes related to mmf were, in 1 patient each, pneumonia and influenza (same patient), herpes zoster, urinary retention, chronic obstructive pulmonary disease and skin ulcer infusion-related reactions • irrs in the rituximab arm occurred primarily at the 1st infusion and frequency decreased with subsequent infusions – 17.9% (1st infusion), 4.5% (2nd infusion), 3% (3rd infusion) and 3% (4th infusion) • irrs were grade 1 or 2 in 11 of 15 patients • 3 rituximab patients experienced serious (life-threatening) irrs that led to discontinuation of infusions and withdrawal from treatment – 2 patients (1st infusion), 1 patient (2nd infusion) – all serious irrs resolved with symptomatic treatment • irrs in pv patients were consistent with those seen in patients in other autoimmune indications, both in clinical trials and in the post-marketing setting infections • all serious infections resolved and in the rituximab arm, none led to treatment withdrawal corticosteroid-related adverse events • more patients experienced grade 3 or higher cs-related aes in the mmf arm compared to the rituximab arm conclusions • in patients with moderate to severe pv, the efficacy of rituximab was superior to mmf – the primary efficacy endpoint, sustained croff prednisone ≥ 16 weeks, was statistically significant in favor of rituximab – all ranked secondary efficacy endpoints were statistically significant in favor of rituximab • the safety profile of rituximab was manageable with an acceptable tolerability, consistent with the known rituximab safety profile in the approved autoimmune indications • rituximab has a superior overall benefit-risk profile compared to mmf in patients with moderate to severe pv references 1. murrell df, et al. j am acad dermatol. 2018 feb 10 [epub ahead of print] 2. rituxan (rituximab) [prescribing information]. genentech, inc., 2019. 3. mabthera (rituximab) [summary of product characteristics]. roche, 2019. 4. joly p, et al. lancet. 2017;389:2031-2040 5. chen dm, et al. british j dermatol. 2019 sep 5. [epub ahead of print] 6. beissert s, et al. j invest dermatol. 2010;130:2041-2048. 7. boulard c, et al. br j dermatol 2016;175:142-149. acknowledgments all patients who participated in the trial, the pemphix investigators, study sites and research coordinators and staff, research and development staff at roche and genentech, and the international pemphigus and pemphigoid foundation. author disclosures v. p. werth: consultant for and grant from genentech; p. joly: consultant for roche, amgen, principia biopharma, argenx; d. mimouni: no disclosures; e. maverakis: no disclosures; p. lehane: employee of roche; l. gearhart: employee of roche; p. pordeli: employee of roche; d. m. chen: employee of genentech skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 143 brief articles reactive angioendotheliomatosis: a case report naeha gupta do1, payvand kamrani bs2, nektarios lountzis md3, richard mcclain md3 1lehigh valley health network, allentown, pa 2philadelphia college of osteopathic medicine, philadelphia, pa 3advanced dermatology associates, allentown, pa a 59-year-old gentleman presented with a lesion on his left thigh that had been present for three months (figure a). the lesion was initially described as a spontaneous lemonsized pink area that later progressed to an increasingly painful plaque with central crusting. prior to examination in our office, he was evaluated by vascular surgery due to left lower extremity pain. ultrasound performed by vascular surgery showed left iliac artery stenosis and partial occlusion. patient was scheduled for vascular intervention pending evaluation and clearance by dermatology for the new onset skin changes. he had no history of similar lesions in the past, but did have a previous history three years prior of a left femoral tibioperoneal trunk bypass. within the past three months, the patient’s medical history had also been complicated by cerebrovascular accident, myocardial infarction, and acute pancreatitis. while the cause of the pancreatitis was not definitively determined, the patient did have a history of alcohol abuse and hyperlipidemia. on physical examination, the patient had a large pink-red plaque on left medial thigh with a small amount of scaling, and central white induration with a thicker dark brown crust. the right lower extremity was clear. laboratory findings revealed a low hemoglobin of 11.7 (reference range, 12.017.0 g/dl), elevated platelets of 418 (reference range, 149-390 thousands/ul), elevated fibrinogen of 503 (reference range, 227-495 mg/dl), and an elevated case report reactive angioendotheliomatosis (rae) is a rare, typically self-limiting, angioproliferative disease that is commonly seen in patients with a variety of inflammatory and systemic diseases. rae can clinically present as ulcerated, single or multifocal, violaceous papules or plaques. we report a case of a 59-year-old male with a complicated cardiac history who presented with biopsy-proven rae on the thigh. the differential diagnosis of rae can include kaposi sarcoma and angiosarcoma, as well as other non-malignant cutaneous diseases. these diagnoses must be excluded before correctly diagnosing and treating rae. we review the common presentation of rae along with criteria to exclude other possible diagnoses that can resemble rae. abstract skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 144 erythrocyte sedimentation rate of 36 (reference range, 0-11 mm/hr). two punch biopsies were obtained to aid with diagnosis, one from the central white indurated area and one from the peripheral pink-red zone (figures b and c). histopathologic examination of both biopsies from the left thigh revealed an ill-defined dermal-based proliferation of poorly formed slit-like vascular spaces that percolated through reticular collagen bundles, surrounded adnexal structures and extended into the subcutis. the vascular spaces were lined with flattened, bland endothelial cells without cytologic atypia or mitotic activity. cd31 and cd34 immunostains highlighted the patchy vascular proliferation. hhv-8 immunostain was negative. following this initial evaluation in our office, the patient was lost to dermatologic follow up. however, a review of a shared electronic medical record revealed that less than two months later, he had a revascularization procedure of the left femoral and left iliac arteries. patient was discharged to short term rehabilitation. patient did have complications shortly thereafter with wound healing requiring wound debridement and a wound vacuum device. patient did not respond to requests to contact the office. reactive angioendotheliomatosis (rae) is a rare, benign condition that presents with a cutaneous vascular proliferation and tends to occur in patients with coexistent systemic diseases.1 clinical presentation typically includes erythematous macules, purpuric papules, and purpuric plaques, which can be ulcerated.1 although lesions tend to favor the limbs, they can also present on the face or trunk.1–3 rae has been reported in all age groups and is equally common in both males and females.2 review of systems may be positive for constitutional symptoms, such as fevers and weight loss.2,3 laboratory results may demonstrate an elevated erythrocyte sedimentation rate.2 coexistent diseases are broadly reported in the literature and include infectious diseases, systemic diseases, hematologic disorders, monoclonal gammopathies, and vascular abnormalities. while the pathogenesis is unknown, changes in portal and systemic hemodynamics, as well as a response to local hypoxia, have been suggested. this is further supported by cases of rae that improve after arterial bypass procedures, corroborating the notion that local tissue hypoxia may have been an inciting agent leading to induction of angiogenesis.1 another theory is that deposition of complement and immunoglobulins may induce vascular injury and reactive angiogenesis.1 furthermore, association with underlying systemic infections suggest that rae can represent a hypersensitivity response of endothelial cells to foreign antigens.1 this hypersensitivity response leads to deposition of immunoglobulins in capillaries in the skin leading to thrombi, ensuing local hypoxia and, again, subsequent angiogenesis.1-3 on histopathology, rae demonstrates a benign intraluminal proliferation of endothelial cells that may occlude the vascular lumen.4–6 in addition, the vessels are usually dilated.4 the upper subcutaneous fat might demonstrate vascular occlusion with cells and fibrin.2 the intravascular cells are positive for factor viiirelated antigen, cd31, and cd34.4 initially, rae was divided into benign and malignant variants. the malignant variant, incorrectly named malignant discussion skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 145 angioendotheliomatosis, has now been redefined as angiotropic large cell lymphoma/intravascular large b-cell lymphoma, an intravascular type of malignant lymphoma.3 angiotropic large cell lymphoma is a rare extranodal lymphoma characterized by neoplastic lymphocytes in the lumina of blood vessels that can present similar to rae: erythematous, violaceous plaques with ulcerated nodules.9 angiotropic large cell lymphoma will show atypia of intraluminal cells in skin biopsy specimens and intrasinusoidal infiltration of lymphoid cells in bone-marrow specimens.3,9 angiotropic large cell lymphoma is mostly of b-cell origin (positive for cd20 and cd79a immunomarkers) but rare cases can demonstrate a t-cell or nk-cell phenotype (positive for cd2 and cd3; negative for cd4 and cd5; variable expression of cd56, ebv and cd30).2,13 in addition, rae must be distinguished from intralymphatic histiocytosis and intravascular papillary endothelial hyperplasia on histopathology. intravascular papillary endothelial hyperplasia is a nonneoplastic reactive process that arises within blood vessels after vascular trauma. this vascular injury results in thrombus formation, inflammation which facilitates endothelial cell proliferation.10 histologically, intravascular papillary endothelial hyperplasia demonstrates thin-walled dilated blood vessels with a thrombus and hyaline papillary fronds lined by endothelial cells.3 intralymphatic histiocytosis is a disorder defined by the accumulation of histiocytes within lymphatic vessels and clinically presents as asymmetric plaques, nodules or macules.11 intralympathic histiocytosis shows intraluminal proliferations with occlusion whereas rae shows intraluminal glomeruli-like tufts of capillaries.3 the majority of the intraluminal cells expresses positive cd68 and negative cd31/cd34 with marked dermal edema and perivascular inflammatory infiltrate.4,11 other important clinical entities to consider include kaposi’s sarcoma and angiosarcoma. kaposi sarcoma (ks) presents initially as erythematous, violaceous bilateral and symmetric patches, typically on the lower extremities.7 ks can range from an isolated cutaneous involvement to a rapidly progressive cutaneous, mucosal, and visceral disseminated disease.7 histopathology varies depending on the phase of the disease. early ks resembles granulation tissue and small vessel-like proliferation.7 as the lesions progress, endothelized vessels with slit-like spaces cuffed by oval and spindle cells infiltrating dermal collagen bundles will evolve. hhv-8 has been closely linked with all types of ks.7 angiosarcoma is a malignant neoplasm derived from vascular endothelial cells that presents as a hematoma-like lesion, sometimes as a consequence of radiation therapy or chronic lymphedema, around the eighth decade of life .8. the majority of cases involve the upper extremity of women who have undergone radical mastectomy for the treatment of breast cancer but can also be seen on the sun exposed head and neck of elderly males.8,12 this diagnosis can be excluded by its distinct histopathological features, which include irregular, anastomosing vascular structures with pleomorphic and hyperchromatic atypical endothelial cells.8 skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 146 figure a. clinical presentation of left thigh of 59year-old male showed reactive angioendotheliomatosis presenting as progressively enlarging, tender, erythematous plaque with central ulcerations. figure b. h&e of biopsy 2 at 4x. showing poorlydemarcated dermal based proliferation of slit-like vascular spaces throughout reticular collagen bundles. figure c. h&e x 4x. cd34 stain showing patchy proliferation of capillaries throughout the dermis. rae is typically self-limiting with a favorable prognosis.1 therapy, if needed, is directed at the underlying systemic disease. however, no specific treatment is currently available. consideration can be made for antibiotics for infections and systemic steroids for their suppressive role on neoangiogenesis when no apparent cause can be found.3 in all, rae is a rare reactive endothelial proliferation associated with numerous conditions in response to an unknown inciting stimulus. conflict of interest disclosures: none funding: none corresponding author: naeha gupta, do lehigh valley health network 1259 s. cedar crest blvd. allentown, pa 18103 phone: 610-437-4134 fax: 610-437-2118 email: gupta.naeha@gmail.com conclusion mailto:gupta.naeha@gmail.com skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 147 references: 1. mcmenamin me, fletcher cdm. reactive angioendotheliomatosis. am j surg pathol. 2002;26(6):685-697. 2. lazova r, slater c, scott g. reactive angioendotheliomatosis: case report and review of the literature. am j dermatopathol. 1996;18(1):63-69. 3. rongioletti f, rebora a. cutaneous reactive angiomatoses: patterns and classification of reactive vascular proliferation. j am acad dermatol. 2003;49(5):887-896. 4. aung pp, ballester ly, goldberg lj, bhawan j. incidental simultaneous finding of intravascular histiocytosis and reactive angioendotheliomatosis. am j dermatopathol. 2015;37(5):401-404. 5. mazloom se, stallings a, kyei a. differentiating intralymphatic histiocytosis, intravascular histiocytosis, and subtypes of reactive angioendotheliomatosis: review of clinical and histologic features of all cases reported to date. am j dermatopathol. 2017;39(1):33-39. 6. kim s, elenitsas r, james w. diffuse dermal angiomatosis. arch dermatology. 2002;138:456458. 7. schwarz r, micali g, nasca m, scuderi l. kaposi sarcoma: a continuing conundrum. j am acad dermatol. 2018;59(2):179-206. 8. shustef e, kazlouskaya v, prieto vg, et al. cutaneous angiosarcoma: a current update. journal of clinical pathology 2017;70:917-925. 9. kruse l, buescher l, nietert e. intravascular bcell lymphoma presenting as retiform purpura. j am acad dermatol. 2002;67(5):238-240. 10. boukovalas s, dillard r, qiu s, cole e. intravascular papillary endothelial hyperplasia (masson’s tumor): diagnosis the plastic surgeon should be aware of. plast reconstr surg glob open. 2017;5(1):1122. 11. barba e, colato c, girolomoni g. intralympathic histiocytosis: a case report and review of literature. j cutan pathol. 2010;42:593-599. 12. mendenhall, w. m., mendenhall, c. m., werning, j. w., reith, j. d., & mendenhall, n. p. (2006). cutaneous angiosarcoma. american journal of clinical oncology, 29(5), 524-528. 13. alegría-landa v, manzarbeitia f, salvatierra calderón mg, requena l, rodríguez-pinilla sm. cutaneous intravascular natural killer/t cell lymphoma with peculiar immunophenotype. histopathology. 2017 dec;71(6):994-1002. microsoft word july 2020 covidcon 908 proof returned.docx skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 335 covid concepts considerations for dermatologic patient care during covid-19 clay j. cockerell, md, mba1,2, haley d. heibel, md3, ashleigh workman, do4,5 1cockerell dermatopathology, dallas, tx 2departments of dermatology and pathology, ut southwestern medical center, dallas, tx 3department of pediatrics, suny downstate health sciences university, brooklyn, ny 4department of dermatology, medical city weatherford, weatherford, tx 5department of dermatology, university of north texas health science center, fort worth, tx to the editor: the covid-19 pandemic has led to numerous challenges in dermatology. dermatologists have experienced uncertainty regarding the extent of procedures that are permitted during the pandemic. for instance, the attorney general of texas issued a statement that dermatologists were not allowed to perform “routine” procedures during the pandemic. the ambiguous nature of “routine” procedures was misinterpreted by many dermatologists, unfortunately leading to the delay of biopsies and surgeries for skin cancer. during the covid-19 era, we have seen multiple metastatic melanomas, as well as cutaneous metastatic lung cancer and, in another patient, cutaneous metastatic breast cancer. consideration should be placed on the potential for perceived and existing barriers for patients receiving dermatologic care with teledermatology during the covid-19 era. delaying surgery for skin cancer has the potential to increase tumor burden, which may lead to more complex surgeries and increase the risk for metastasis.1 skin manifestations may be one of the first signs of covid-19.2 recalcati found that of the 20% of patients who developed cutaneous manifestations during the course of covid, 44% had cutaneous involvement at disease onset.2 if patients developed concerning skin lesions or experienced complications from a pre-existing skin condition and had difficulty in connecting with or receiving care from a dermatologist, they likely sought care from an urgent care center or emergency room. these centers were already overwhelmed, and the patient abstract the covid-19 pandemic has led to numerous challenges in dermatology. here, we discuss our experience of diagnosing multiple metastatic cutaneous cancers during the covid-19 era and consider how perceived and existing barriers for patients receiving dermatologic care in the pandemic may have led to the progression of cancer. in texas, the attorney general issued a statement that dermatologists could not perform “routine” procedures. unfortunately, many dermatologists delayed biopsies and surgeries for skin cancer due to misinterpreting the ambiguous nature of the term “routine.” dermatologists provide valuable expertise and crucial services to society at all times, including during life-threatening pandemics, and this should be emphasized to the public and governmental agencies. skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 336 was placed in a circumstance that led to a higher chance of exposure to covid-19. unintended consequences of dermatologic patients seeking care from other facilities include utilization of resources reserved for covid-19 patients and inappropriate diagnosis and treatment, leading to further spread of covid-19. dermatologists have experience in the recognition of cutaneous manifestations of systemic disease and were the first to recognize dermatologic signs of covid-19, which is of value to society. through early recognition of infected and contagious patients with cutaneous signs of covid-19 and isolating these patients, dermatologists could have reduced the spread of covid-19. dermatologists must also consider the potential harm of delaying an in-person visit with a patient and/or procedure against the potential spread of covid-19. teledermatology allows for evaluation of patients without increasing the risk of infection, but not all patients have the desire, ability, or resources to participate in teledermatology. additionally, it may not be possible to evaluate some dermatologic conditions or perform full body examinations via teledermatology.3 in the era of teledermatology, we encourage thoughtful considerations in providing access for patient care, while also considering reducing the transmission of covid-19. it may be helpful for dermatologists to provide clear contact information and guidelines for the evaluation of an urgent patient.4 dermatologists provide valuable expertise in the diagnosis and treatment of various skin conditions. this is a cautionary reminder of the importance of our specialty, not to be trivialized by third parties, such as governmental agencies. it must be emphasized to the public that the field of dermatology is not limited to cosmetic services. dermatologists provide valuable and crucial services at all times, including during life-threatening pandemics. conflict of interest disclosures: none funding: none corresponding author: clay j. cockerell, md, mba 2110 research row suite 100 dallas, tx 75235 phone: 214-530-5200 email: ccockerell@dermpath.com references: 1. der sarkissian sa, kim l, veness m, yiasemides e, sebaratnam df. recommendations on dermatologic surgery during the covid-19 pandemic. j am acad dermatol. 2020. 2. recalcati s. cutaneous manifestations in covid-19: a first perspective. j eur acad dermatol venereol. 2020;34(5):e212-e213. 3. pathoulas jt, stoff bk, lee kc, farah rs. ethical outpatient dermatology care during the coronavirus (covid-19) pandemic. j am acad dermatol. 2020;82(5):1272-1273. 4. lee i, kovarik c, tejasvi t, pizarro m, lipoff jb. telehealth: helping your patients and practice survive and thrive during the covid-19 crisis with rapid quality implementation. j am acad dermatol. 2020;82(5):1213-1214. april armstrong,1 mark lebwohl,2 linda stein gold,3 abby jacobson4 1university of southern california, los angeles, ca; 2icahn school of medicine at mount sinai, new york, ny; 3henry ford health system, west bloomfield, mi; 4ortho dermatologics (a division of bausch health us, llc), bridgewater, nj table 1. median times to achieve therapeutic response (amagine-2/-3) • brodalumab treatment was associated with greater proportions of psi total responders (defined as weekly average psi total score ≤8, with no item scores >1) and psi itch responders (defined as weekly average psi itch score ≤1; p<0.0001) vs ustekinumab, indicating a rapid reduction in patient-reported symptom severity (amagine-2/-3; figure 2)8 – additionally, a significantly greater proportion of patients treated with brodalumab vs ustekinumab achieved a psi total score of 0 at week 12 (22.7% vs 13.4%; p<0.001)8 figure 2. brodalumab treatment was associated with a faster onset of symptom improvement, assessed via proportion of psi responders, vs ustekinumab8 in amagine-2/-3 for (a) psi total score and (b) psi itch score. psi, psoriasis symptom inventory. adefined as weekly average psi total score ≤8, with no item scores >1. bdefined as weekly average psi itch score ≤1. *p<0.0001. • significant improvements in quality-of-life measures (≥5-point dlqi improvement from baseline) were seen as early as week 2 among patients treated with brodalumab vs placebo (p<0.001; amagine-1/-2/-3; figure 3)9 – furthermore, complete skin clearance with brodalumab was associated with greater improvements in dlqi; 60.9% of patients who achieved pasi 100 attained a dlqi score of 0 at week 12, vs 20.5% of patients who achieved pasi 75 to <905,9 figure 3. patients treated with brodalumab experienced rapid improvement in quality of life in amagine-1/-2/-3. dlqi, dermatology life quality index. *p<0.001. indirect comparison of brodalumab and other psoriasis biologics • in an indirect comparison, brodalumab treatment resulted in faster time to response (mean time for 50% of patients to achieve pasi 90) than other psoriasis biologics, including ixekizumab and secukinumab (6.2 vs 7.4 and 16.3 weeks, respectively; table 2)6 table 2. indirect comparison of time to response6 brodalumab provides rapid onset of therapeutic response for patients with moderate-to-severe psoriasis objective • to characterize the time to response of brodalumab by directly comparing brodalumab with ustekinumab or placebo in clinical studies and by indirectly comparing brodalumab with other psoriasis biologics conclusions • onset of response was more rapid than other psoriasis biologics in direct and indirect comparisons • brodalumab provides a safe and effective treatment option, with rapid onset of symptom relief and improvements in quality of life, for adult patients with moderate-to-severe psoriasis synopsis • several factors should be considered when selecting the most appropriate treatment of moderate-to-severe psoriasis, including drug effectiveness, potential adverse events, and time to response1 • the human anti–interleukin-17 receptor a monoclonal antibody brodalumab has been shown to be safe and effective for moderate-to-severe psoriasis in adults and improves clinical outcomes more rapidly than other psoriasis biologics2 methods • this post hoc analysis directly compares time to response of brodalumab vs ustekinumab or placebo in three phase 3 studies (amagine-1/-2/-3), measured by the following: – psoriasis area and severity index (pasi) responses from baseline (amagine-2/-3)3 – psoriasis symptom improvement, assessed with the psoriasis symptom inventory (psi; amagine-2/-3); for the psi, patients rank the severity of 8 symptoms (itch, redness, scaling, burning, cracking, stinging, flaking, and pain) on a 5-point scale ranging from 0 (not at all) to 4 (very severe), and individual item scores are combined for a total score ranging from 0 to 324 – changes in patient-reported quality of life, assessed with the dermatology life quality index (dlqi; amagine-1/-2/-3)5 • time to onset of therapeutic response of brodalumab is also indirectly compared with that of other psoriasis biologics6 results clinical studies of brodalumab (amagine-1/-2/-3) • significant differences in speed of efficacy between brodalumab and ustekinumab were seen as early as week 1, in which 3.5% of brodalumabtreated patients achieved ≥75% reduction from baseline in pasi (pasi 75), vs 0.2% of ustekinumab-treated patients (p<0.001; amagine-2/-3; figure 1)3 – median times to achieve pasi 25, pasi 50, or pasi 75 (table 1) and median times for 50% of patients to achieve pasi 75, pasi 90, or pasi 100 were significantly shorter with brodalumab vs ustekinumab (p<0.001 for all analyses)3,7 figure 1. pasi 75 responders through week 12 among patients treated with brodalumab or ustekinumab in amagine-2/-3.3 pasi 75, ≥75% reduction from baseline in psoriasis area and severity index. *p<0.001. funding: this study was sponsored by ortho dermatologics. medical writing support was provided by medthink scicom and funded by ortho dermatologics. ortho dermatologics is a division of bausch health us, llc. author disclosures: aa, ml, and lsg report the following financial disclosures related to the presentation: serving as a research investigator, speaker, or scientific advisor for ortho dermatologics (a division of bausch health us, llc). aj is an employee of ortho dermatologics (a division of bausch health us, llc). references: 1. thibodeaux et al. skin the journal of cutaneous medicine. 2019;3:368-373. 2. lebwohl et al. n engl j med. 2015;373:1318-1328. 3. blauvelt et al. j am acad dermatol. 2017;77:372-374. 4. gordon et al. br j dermatol. 2014;170:705-715. 5. wu. am j manag care. 2017;23(21 suppl):s403-s416. 6. egeberg et al. j eur acad dermatol venereol. 2020;34:39-46. 7. blauvelt et al. slides presented at: annual meeting of the american academy of dermatology; march 3-7, 2017; orlando, fl. 8. gottlieb et al. j eur acad dermatol venereol. 2018;32:1305-1313. 9. data on file, ortho dermatologics (a division of bausch health us, llc). previous presentation information: data included in this poster have been previously presented in full at the 2nd annual innovations in dermatology fall conference; november 3-5, 2022; virtual and las vegas, nv. 3.5 22.5 59.6 75.8 85.7 0.2 3.1 16.5 38.5 69.7 0 20 40 60 80 100 week 1 week 2 week 4 week 6 week 12 pa si 7 5 re sp o nd er s, % brodalumab (n=1236) ustekinumab (n=613) * * * * * 72.1 82.8 85.5 86.9 27.1 31.5 29.3 28.0 0 20 40 60 80 100 week 2 week 4 week 8 week 12 brodalumab (n=1314) placebo (n=753) * * * * ≥ 5po in t d lq i i m pr o ve m en t fr o m b as el in e, % 22.1 52.3 60.2 63.5 6.8 20.2 35.7 44.0 0 20 40 60 80 100 week 2 week 4 week 6 week 8 ps i t o ta l r es po nd er s, % psi total respondersaa 36.4 63.8 69.3 71.8 17.1 33.0 47.1 57.1 0 20 40 60 80 100 week 2 week 4 week 6 week 8 ps i i tc h re sp o nd er s, % psi itch respondersbb * * * * brodalumab (n=1236) ustekinumab (n=613) presented at winter clinical dermatology conference hawaii ® • january 13-18, 2023 • kohala coast, hi ## median time, weeks brodalumab (n=1236) ustekinumab (n=613) p value time to achieve pasi 75 4.2 9.4 <0.0001 time to achieve pasi 50 1.8 4.5 <0.0001 time to achieve pasi 25 0.8 1.8 <0.0001 pasi 25, 50, and 75, ≥25%, ≥50%, or ≥75% reduction from baseline in psoriasis area and severity index. proportion of patients achieving pasi, weighted mean (sd) time, weeks brodalumab ixekizumab secukinumab time for 50% to achieve pasi 90 6.2a 7.4 (0.7) 16.3 (6.2) time for 25% to achieve pasi 100 6.9 (0.9) 8.1 (1.2) 15.1 (0.4) pasi 90 and 100, ≥90% or 100% reduction from baseline in psoriasis area and severity index. aonly one study cohort. objective to evaluate the effect of bodyweight on response to bimekizumab (bkz) when dosed 320 mg every 4 weeks (q4w) or every 8 weeks (q8w) during maintenance treatment, following an initial 16 weeks of treatment with 320 mg q4w. introduction • increased bodyweight may affect response to biologic treatments in patients with moderate to severe plaque psoriasis.1 • here, we report the efficacy and safety of bkz dosing regimens over 48 weeks using data pooled from four phase 3/3b studies in patients with moderate to severe plaque psoriasis categorised by bodyweight at baseline. materials and methods • data were pooled from three bkz in plaque psoriasis phase 3/3b trials: be sure (nct03412747), be vivid (nct03370133) and be radiant (nct03536884).2–4 for safety analyses, and efficacy analyses over the initial 16-week period, the phase 3 randomized withdrawal trial be ready (nct03410992) was also included.5 • analyses included patients who were randomized to bkz 320 mg q4w for 16 weeks. at week 16, patients could either continue on bkz 320 mg q4w (q4w/q4w) or switch to bkz 320 mg q8w (q4w/q8w) for maintenance treatment to week 48. • patients were categorised by baseline bodyweight: <120 kg and ≥120 kg. 120 kg was identified as a potential weight threshold above which efficacy may differ between dosing regimens based on pk-pd modelling. • missing efficacy data were imputed as non-response (nri). • safety analyses were conducted during the maintenance period (weeks 16–48) by maintenance dosing regimen (q4w versus q8w). • treatment-emergent adverse events (teaes) were coded using meddra v19.0. results • baseline characteristics for patients categorised by bodyweight are presented in table 1. • 116/1,362 (8.5%) patients included in efficacy analyses to week 16 had bodyweight ≥120 kg (figure 1). • at week 16, pasi 90, pasi 100 and iga 0 responses for all patients randomized to bkz 320 mg q4w were higher in patients <120 kg vs ≥120 kg (table 2). • 88/975 (9.0%) patients included in the maintenance period efficacy analyses had bodyweight ≥120 kg. • for patients <120 kg, week 16 pasi 90, pasi 100 and iga 0 response rates were maintained to week 48 for both dose regimens (table 2; figure 2a). • for patients ≥120 kg, greater increases in the proportions of patients achieving pasi 100 and iga 0 were observed in those receiving bkz q4w/q4w vs bkz q4w/q8w between week 16 and week 48 (table 2; figure 2b). • among patients ≥120 kg who did not achieve pasi 100 at week 16 (n=51), a greater proportion of those who continued on bkz 320 mg q4w achieved pasi 100 at week 48 compared with those who switched to bkz 320 mg q8w (figure 3). • the three most common teaes across both bodyweight categories and dosing regimens were nasopharyngitis, oral candidiasis and upper respiratory tract infection. no safety concerns were identified that would preclude bkz 320 mg q4w/q4w maintenance dosing in patients ≥120 kg who may benefit from more frequent dosing (table 3). summary presented at the 42nd annual fall clinical dermatology conference | las vegas, nv | october 20–23, 2022 conclusions at week 48, for patients <120 kg, pasi 100 and iga 0 response rates were similar regardless of maintenance dosing regimen (q4w vs q8w). for patients ≥120 kg, higher responses were observed when bkz was dosed q4w vs q8w. andreas pinter,1 bruce strober,2,3 david rosmarin,4 paolo gisondi,5 veerle vanvoorden,6 luke peterson,7 cynthia madden,7 dirk de cuyper,6 richard b. warren8 bimekizumab in patients with moderate to severe plaque psoriasis by bodyweight: pooled results from phase 3 trials previously presented at g2c 2021 institutions: 1department of dermatology, venereology and allergology, goethe-university, frankfurt am main, germany; 2yale university, new haven, connecticut, usa; 3central connecticut dermatology research, cromwell, connecticut, usa; 4department of dermatology, tufts medical center, boston, massachusetts, usa; 5dermatology and venereology, department of medicine, università di verona, verona, italy; 6ucb pharma, brussels, belgium; 7ucb pharma, raleigh, north carolina, usa; 8dermatology centre, salford royal nhs foundation trust, manchester nihr biomedical research centre, the university of manchester, manchester, uk. references: 1puig l. j eur acad dermatol 2011;25:1,007–011; 2warren rb. n engl j med 2021;385:130–41; 3reich k. lancet 2021;397:487–98; 4reich k. n engl j med 2021;385:142–52; 5gordon kb. lancet 2021;397:475–86. author contributions: substantial contributions to study conception/design, or acquisition/analysis/interpretation of data: ap, bs, dr, pg, vv, lp, cm, ddc, rbw; drafting of the publication, or revising it critically for important intellectual content: ap, bs, dr, pg, vv, lp, cm, ddc, rbw; final approval of the publication: ap, bs, dr, pg, vv, lp, cm, ddc, rbw. author disclosures: ap: investigator and/or speaker and/or advisor for abbvie, almirall, amgen, biogen, boehringer ingelheim, celgene, eli lilly, galderma, gsk, hexal, janssen, leo pharma, mc2, medac, merck serono, mitsubishi pharma, msd, novartis, pfizer, regeneron, roche, sandoz, schering-plough, tigercat pharma, and ucb pharma. bs: consultant (honoraria) for abbvie, almirall, amgen, arcutis, arena, aristea, asana, boehringer ingelheim, bristol myers squibb, connect biopharma, dermavant, eli lilly, epi health, evelo biosciences, immunic therapeutics, janssen, leo pharma, maruho, meiji seika pharma, mindera health, novartis, ono, pfizer, regeneron, sanofi genzyme, sun pharma, ucb pharma, union therapeutics, ventyxbio, and vtv therapeutics; stock options for connect biopharma and mindera health; speaker for abbvie, eli lilly, janssen, regeneron, and sanofi genzyme; scientific co-director (consulting fee) for corevitas (formerly corrona) psoriasis registry; investigator for abbvie, cara, corevitas psoriasis registry, dermavant, dermira, and novartis; editor-in-chief (honorarium) for the journal of psoriasis and psoriatic arthritis. dr: received honoraria as a consultant for abbvie, abcuro, altrubio, boehringer ingelheim, bristol myers squibb, celgene, concert, dermavant, dermira, eli lilly, incyte, janssen, kyowa kirin, novartis, pfizer, regeneron, sanofi, sun pharma, ucb pharma, and vielabio; has received research support from abbvie, amgen, bristol myers squibb, celgene, dermira, eli lilly, galderma, incyte, janssen, merck, novartis, pfizer, and regeneron; and has served as a paid speaker for abbvie, amgen, celgene, eli lilly, janssen, novartis, pfizer, regeneron, and sanofi. pg: consultant for abbvie, abiogen, almirall, celgene, eli lilly, janssen, leo pharma, merck, msd, novartis, otsuka, pfizer, pierre fabre, sanofi, and ucb pharma. vv, lp, cm, ddc: employees and shareholders of ucb pharma. rbw: consulting fees from abbvie, almirall, amgen, arena, astellas, avillion, biogen, bristol myers squibb, boehringer ingelheim, celgene, eli lilly, gsk, janssen, leo pharma, novartis, pfizer, sanofi, and ucb pharma; research grants to his institution from abbvie, almirall, janssen, leo pharma, novartis, and ucb pharma; honoraria from astellas, dice, gsk, and union. acknowledgements: these studies were funded by ucb pharma. rbw is supported by the nihr manchester biomedical centre. we thank the patients and their caregivers in addition to the investigators and their teams who contributed to these studies. the authors acknowledge susanne wiegratz, msc, ucb pharma, monheim, germany for publication coordination, natalie nunez gomez, md, former employee of ucb pharma, monheim, germany for critical review, ruth moulson, mph, costello medical, for medical writing and the design team at costello medical for graphic design assistance. all costs associated with development of this poster were funded by ucb pharma. table 1 baseline characteristics table 2 overview of efficacy outcomes by baseline bodyweight category (nri) bkz: bimekizumab; bsa: body surface area; dlqi: dermatology life quality index; ibd: inflammatory bowel disease; iga 0: score of 0 (clear) with ≥2-category improvement relative to baseline in investigator’s global assessment; il; interleukin; mace: major cardiovascular event; nri: non-responder imputation; pasi 90/100: ≥90/100% improvement from baseline in psoriasis area and severity index; pk-pd: pharmacokinetic-pharmacodynamic; q4w: every 4 weeks; q8w: every 8 weeks; sd: standard deviation; sib: suicidal ideation and behavior; teae: treatment-emergent adverse event; tnf: tumour necrosis factor. figure 1 cumulative eairs for teaes over three years in the phase 2 and 3 trials a) pasi 100 in patients <120 kg b) pasi 100 in patients ≥120 kg data were pooled from four bkz in plaque psoriasis phase 3/3b trials pasi 100 response in patients at week 16 and week 48 by baseline bodyweight categoriesa be sure (nct03412747) be vivid (nct03370133) bodyweight <120 kg bodyweight ≥120 kg bkz q4w (n=1,246) bkz q4w (n=116) age (years), mean ± sd 45.1 ± 13.8 45.3 ± 11.7 male, n (%) 858 (68.9) 91 (78.4) caucasian, n (%) 1079 (86.6) 109 (94.0) weight (kg), mean ± sd 85.5 ± 17.1 135.0 ± 17.0 disease duration (years), mean ± sd 18.2 ± 12.7 19.3 ± 11.8 pasi, mean ± sd 20.6 ± 7.5 21.8 ± 8.7 bsa (%), mean ± sd 25.7 ± 15.4 28.6 ± 17.3 iga score, n (%) 2: mild 3 (0.2) 0 3: moderate 831 (66.7) 65 (56.0) 4: severe 412 (33.1) 51 (44.0) dlqi total score, mean ± sd 10.6 ± 6.5 9.6 ± 5.9 prior systemic therapy, n (%) 961 (77.1) 77 (66.4) prior biologic therapy, n (%) 464 (37.2) 41 (35.3) anti-tnf 192 (15.4) 16 (13.8) anti-il-17 248 (19.9) 22 (19.0) anti-il-23 133 (10.7) 16 (13.8) baseline characteristics are reported using data for the initial treatment period from be sure, be vivid, be radiant and be ready. following an initial 16 weeks of treatment with bkz 320 mg q4w, patients could either continue on bkz 320 mg q4w (q4w/q4w) or switch to bkz 320 mg q8w (q4w/q8w). bodyweight <120 kg bodyweight ≥120 kg bkz q4w (n=1,246), % bkz q4w (n=116), % week 16a pasi 90 87.7 78.4 pasi 100 64.3 42.2 iga 0 65.4 42.2 bkz q4w/q4w (n=555), % bkz q4w/q8w (n=332), % bkz q4w/q4w (n=51), % bkz q4w/q8w (n=37), % week 16b pasi 90 88.6 90.4 84.3 83.8 pasi 100 62.5 68.4 39.2 45.9 iga 0 63.4 69.9 37.3 45.9 week 48b pasi 90 87.4 86.7 76.5 83.8 pasi 100 72.1 69.9 68.6 51.4 iga 0 72.4 70.8 68.6 51.4 table 3 summary of teaes during the maintenance period (weeks 16–48) figure 2 pasi 100 responses through weeks 16–48 by baseline bodyweight category (nri) figure 3 pasi 100 responses through weeks 16–48 in week 16 pasi 100 non-responder patients ≥120 kg (nri) bodyweight <120 kg bodyweight ≥120 kg bkz q4w/q4w (n=659) n (%) bkz q4w/q8w (n=429) n (%) bkz q4w/q4w (n=55) n (%) bkz q4w/q8w (n=43) n (%) any teae 492 (74.7) 328 (76.5) 42 (76.4) 31 (72.1) serious teaes 21 (3.2) 18 (4.2) 4 (7.3) 2 (4.7) discontinuations due to teaes 17 (2.6) 7 (1.6) 2 (3.6) 1 (2.3) drug-related teaes 196 (29.7) 131 (30.5) 16 (29.1) 10 (23.3) severe teaes 18 (2.7) 20 (4.7) 5 (9.1) 2 (4.7) deaths 0 1 (0.2) 1 (1.8) 0 three most common teaes nasopharyngitis 101 (15.3) 79 (18.4) 11 (20.0) 5 (11.6) oral candidiasis 82 (12.4) 57 (13.3) 4 (7.3) 5 (11.6) upper respiratory tract infection 44 (6.7) 38 (8.9) 7 (12.7) 4 (9.3) teaes of interest serious infections 5 (0.8) 8 (1.9) 1 (1.8) 0 ibd 0 0 0 0 adjudicated sib 1 (0.2) 0 0 0 malignancies 2 (0.3) 4 (0.9) 0 1 (2.3) serious hypersensitivity reactions 0 0 0 0 adjudicated mace 3 (0.5) 1 (0.2) 0 0 hepatic events 14 (2.1) 14 (3.3) 1 (1.8) 1 (2.3) safety data from the randomized withdrawal trial be ready are included. data collected after the point of escape in be ready are excluded. data were pooled from be sure, be vivid, be radiant and be ready. patient numbers presented during the maintenance period are those for the maintenance period safety set. for the maintenance period efficacy analysis set, of patients <120 kg, 555 received bkz q4w/q4w and 332 recieved bkz q4w/q8w and of patients ≥120 kg, 51 received bkz q4w/q4w and 37 received bkz q4w/q8w. analyses include patients who were randomized to bkz 320 mg q4w for 16 weeks. at week 16, patients could either continue on bkz 320 mg q4w (q4w/q4w) or switch to bkz 320 mg q8w (q4w/q8w) for maintenance treatment to week 48. [a] data reported include data pooled from be sure, be vivid, be radiant and be ready; [b] data reported are for the maintenance efficacy set, including data pooled from be sure, be vivid and be radiant. data reported are for the maintenance efficacy set, including data pooled from be sure, be vivid and be radiant. data reported are for the maintenance efficacy set, including data pooled from be sure, be vivid and be radiant. intial treatment period bkz 320 mg q4w (n=1,362) <120 kg (n=1,246) ≥120 kg (n=116) maintenance period baseline week 48week 16 bkz 320 mg q4w/q4w <120 kg (n=659) ≥120 kg (n=55) bkz 320 mg q4w/q8w <120 kg (n=429) ≥120 kg (n=43) be sure2 be vivid3 be radiant4 be ready5 20 24 28 32 36 40 44 4816 0 25 50 75 100 week p ro p o rt io n o f p a ti e n ts a c h ie v in g p a s i 1 0 0 ( % ) 62.5% 68.4% 72.1% 69.9% bkz 320 mg q4w/q4w (n=555) bkz 320 mg q4w/q8w (n=332) 20 24 28 32 36 40 44 4816 0 25 50 75 100 week p ro p o rt io n o f p a ti e n ts a c h ie v in g p a s i 1 0 0 ( % ) 39.2% 45.9% 68.6% 51.4% bkz 320 mg q4w/q4w (n=51) bkz 320 mg q4w/q8w (n=37) 20 24 28 32 36 40 44 4816 0 25 50 75 100 week p ro p o rt io n o f p a ti e n ts a c h ie v in g p a s i 1 0 0 ( % ) 54.8% 25.0% bkz 320 mg q4w/q4w (n=31) bkz 320 mg q4w/q8w (n=20) 100 75 50 25 0p ro p o rt io n o f p a ti e n ts a c h ie vi n g p a s i 10 0 ( % ) patients <120 kg (n=1,246) 64.3 patients ≥120 kg (n=116) 42.2 week 16 patients <120 kg 72.1 patients ≥120 kg 69.9 68.6 51.4 week 48 bkz 320 mg q4w bkz 320 mg q4w/q4w bkz 320 mg q4w/q8w (n=555) (n=332) (n=51) (n=37) be ready (nct03410992) be radiant (nct03536884) at week 16, a greater proportion of patients <120 kg achieved pasi 100 vs those ≥120 kg. at week 48, higher pasi 100 responses were observed in patients ≥120 kg receiving bkz q4w vs q8w, supporting use of q4w maintenance dosing in patients ≥120 kg who do not achieve complete skin clearance at week 16. evaluating treatment choice among patients with moderate or severe psoriasis in the united states april w. armstrong,1 sayeli jayade,2 sanika rege,2 namita joshi,2 vardhaman patel,3 david davidson,3 samaneh kalirai,3 daniel wolin,4 kimberly boyle,4 dipen patel,2 lauren seigel3 1keck school of medicine, university of southern california, los angeles, ca; 2open health, bethesda, md; 3bristol myers squibb, princeton, nj; 4rti health solutions, research triangle park, nc presented at the 2022 fall clinical dermatology conference; october 20–23, 2022; las vegas, nv this poster may not be reproduced without written permission from the authors.email for april w. armstrong, md, mph: aprilarmstrong@post.harvard.edu synopsis • while several psoriasis treatments are available and in development, different treatment modalities are associated with varying effectiveness, risks, and economic burden, and these factors are likely to influence patients’ decisions related to their psoriasis treatment1 • this study explored the element of treatment decision-making driven by patient experiences — a cross-sectional, web-based survey captured the demographic and clinical characteristics, treatment attributes affecting therapeutic decisions, and perceptions of a new, hypothetical, once-daily oral psoriasis treatment (deucravacitinib) among patients with moderate to severe plaque psoriasis • understanding the factors that drive patients’ treatment preference is crucial for guiding clinical decision-making objectives primary • to identify factors associated with the choice of a new once-daily oral psoriasis treatment with efficacy superior to that of existing oral therapies in patients with moderate to severe psoriasis currently receiving apremilast, tumor necrosis factor inhibitors (tnfis), ustekinumab, topicals, or nonprescription treatments secondary • to rank the importance of treatment attributes to patients with moderate to severe psoriasis using apremilast, tnfis, ustekinumab, topicals, or nonprescription treatments • to elicit views on a new once-daily oral psoriasis treatment among patients with moderate to severe psoriasis using apremilast, tnfis, ustekinumab, topicals, or nonprescription treatments target product profile (deucravacitinib) • tablet formulation with once-daily dosing • clinical studies showed: — 53% of patients reported clear/mostly clear skin within 4 months — 83% of patients who reported a 75% reduction in psoriasis severity maintained this improvement at 1 year — non-serious adverse events, such as cold-like symptoms, headache, diarrhea, nausea, rash, and risk of herpes infection, led to few discontinuations • regular laboratory monitoring is not required, although pre-initiation testing may be needed • out-of-pocket costs may be similar to those of the alternative psoriasis treatments in consideration methods • a cross-sectional, web-based survey of the demographics and clinical characteristics of patients with psoriasis, their views on treatment characteristics that affect treatment-related decisions, and their perceptions of a new, hypothetical, once-daily oral psoriasis treatment • patients were assigned to predefined treatment groups: apremilast, a tnfi, ustekinumab, a topical therapy/phototherapy, and over-the-counter (otc) treatments or no treatment, based on their self-reported current treatment at the time of the survey • a hypothetical psoriasis treatment profile, described by dosage, efficacy, adverse effects, and out-of-pocket costs, was shown to the patients to elicit their views on: (1) interference with everyday life, (2) convenience, (3) treatment-related anxiety, and likelihood of initiating treatment, both (4) without a safety warning and (5) with a safety warning inclusion criteria • ≥18 years of age • residing in the united states • able to read and understand english • physician-diagnosed (self-reported) moderate or severe plaque psoriasis exclusion criteria • mild psoriasis • lack of online consent for the web-based survey data collection process • the study was reviewed and approved by an institutional review board • the study used a convenience sample of patients with moderate or severe psoriasis who were recruited by global perspectives to collect patient-reported data • patients were asked to complete an electronic patient survey that included questions from patient-reported outcome (pro) instruments and de novo questions • potential survey participants were provided with a link to the survey and completed screening questions to determine eligibility, followed by an informed consent checkbox • the final survey was administered to 882 patients statistical analysis • stepwise multivariable logistic regression was conducted to determine sociodemographic and clinical characteristics associated with the choice of the new treatment among patients who were currently receiving treatment or who had never received treatment — independent variables: treatment group, age, sex, race/ethnicity, psoriasis severity over the past week, comorbidities, disease and treatment duration, presence of psoriatic arthritis (psa) at baseline, number of flares, and number of body regions affected • treatment attributes (route of administration, extent of skin clearance, laboratory monitoring, durability, safety, and dosing frequency) were ranked as an ordinal category (scale of 1–6) by patients • chi-square test was conducted to detect significant differences between patient rankings of each treatment attribute and to assess the variations in patient views on the new oral treatment results • figure 1 shows the responses of the 5 baseline treatment groups surveyed • the study sample included 882 patients (mean age = 45.7 [±12.8] years); the majority were female (67.7%), most were white (74.9%), and their average duration of time since psoriasis diagnosis was 14.9 (±11.8) years (figures 2 and 3; table 1) • of 882 patients, 818 (92.8%) were currently receiving treatment and had been on their current treatment for a mean of 2.9 (±4.8) years (table 2) • with their current treatment regimen, 50.8% of patients in the total study population described their psoriasis over the past week as mild, very mild, or none, while 36.5% reported it as moderate and 12.7% reported it as severe or very severe (table 2) figure 1. targeted baseline treatment groups 344 242 98 98 100 0 50 100 150 200 250 300 350 400 p at ie n ts w h o c o m p le te d s u rv e y, n treatment group group 1: apremilast group 2: tnfi group 3: ustekinumab group 4: topical/phototherapy group 5: exploratorya athe exploratory group included patients who were using nonprescription treatments (n = 36), patients who had never received treatment (n = 17), and patients who had received treatment in the past but were not currently receiving treatment (n = 47). tnfi, tumor necrosis factor inhibitor. figure 2. key baseline characteristics, by sex (a) and race/ethnicitya (b) 74.9% 14.1% 2% 2% 0.2% 2.4% 6.1% white black american indian/ alaska native asian native hawaiian/ other pacific islander other preferred not to answer b.a. male female preferred not to answer 32.0% 67.7% 0.3% apercentages sum to >100% because respondents could select multiple races/ethnicities, as applicable. figure 3. key baseline characteristics for all respondents by insurance typea 13.6% 11.9% 54.5% 21.1% 2.2% 3.4% medicare medicaid employer-sponsored private insurance individually purchased private insurance uninsured military/veterans' coverage apercentages sum to >100% because respondents could select more than 1 insurance type, as applicable. table 1. key baseline characteristics for all respondents by patient age category all respondents (n = 882) mean 45.71 median (q1–q3) 45 range 18–76 q1–q3, quartiles 1–3. table 2. key baseline clinical characteristics parameter statistic or category all respondents, n = 882 (%) treatment status, n (%) currently receiving treatment 818 (92.8) was receiving treatment but has stopped 47 (5.3) never received treatment 17 (1.9) treatment duration, years mean (sd) 2.86 (4.81) median (q1–q3) 1.0 (0.0–3.0) range 0.0–42.0 current treatment type, n (%) over-the-counter nonprescription 225 (27.5) topical prescription steroid 230 (28.1) topical vitamin d analog 49 (6.0) other topical treatment 55 (6.7) ultraviolet light/phototherapy 51 (6.2) apremilast 356 (43.5) ustekinumab 101 (12.3) tnfi treatment 251 (30.7) psoriasis severity over the past week, n (%) none 31 (14.8) very mild 155 (17.6) mild 162 (18.4) moderate 322 (36.5) severe 86 (9.8) very severe 26 (2.9) bsa, body surface area; q1–q3, quartiles 1–3; sd, standard deviation; tnfi, tumor necrosis factor inhibitor. • among patients who were currently receiving treatment or who had never received treatment (n = 835), apremilast (41.2%) and tnfis (29.0%) were the most commonly used treatments, and otc or no treatment was the least common group (6.3%) (table 3) • of patients who had never received treatment, 88.2% expressed intent to start the new oral psoriasis treatment, compared with 80.6% of patients who used nonprescription otc treatment, 75.5% of patients who used ustekinumab, 74.0% of patients who used a tnfi, 69.4% of patients who used topical therapy, and 55.2% of patients who used apremilast (figure 4) • willingness to start the new, once-daily oral treatment was high across all groups, including patients currently using apremilast • in response to questions about the new treatment, 83.7% reported that it would be convenient, 65.0% reported that it would cause less anxiety than an injection or infusion, 55.3% reported that it would interfere less with their everyday life, and 50.2% reported that it would reduce their symptoms more than their current psoriasis treatment (figure 5) table 3. intent to start a new once-daily oral psoriasis treatment variable category intent to start new treatment all, n = 835 (%) yes, n = 555 (%) no, n = 280 (%) treatment group apremilast 344 (41.2) 190 (34.2) 154 (55.0) tnfi 242 (29.0) 179 (32.3) 63 (22.5) ustekinumab 98 (11.7) 74 (13.3) 24 (8.6) topical therapy 98 (11.7) 68 (12.3) 30 (10.7) otc or no treatment 53 (6.3) 44 (7.9) 9 (3.2) race/ethnicity white 610 (73.1) 390 (70.3) 220 (78.6) black 114 (13.7) 95 (17.1) 19 (6.8) asian, american indian/alaska native, native hawaiian/other pacifi c islander 32 (3.8) 21 (3.8) 11 (3.9) preferred not to answer 54 (6.5) 29 (5.2) 25 (8.9) other 25 (3.0) 20 (3.6) 5 (1.8) psoriasis severity over the past week (based on a 6-point scale) none 130 (15.6) 48 (8.6) 82 (29.3) mild 308 (36.9) 197 (35.5) 111 (39.6) moderate 298 (35.7) 228 (41.1) 70 (25.0) severe 99 (11.9) 82 (14.8) 17 (6.1) otc, over the counter; tnfi, tumor necrosis factor inhibitor. figure 4. intent to start a new once-daily oral treatment, by treatment group (a), race/ ethnicity (b), and psoriasis severity over the past week (c), all p < 0.001 55.2% 74.0% 75.5% 69.4% 83.0% 0 10 20 30 40 50 60 70 80 90 100 ap re m ila st tn fi us te ki nu m ab to pi ca l t he ra py w hi te bl ac k pr ef er re d no t to a ns we r ot he r no ne mi ld mo de ra te se ve re ot c or n o tr ea tm en t as ia n, a m er ic an in di an / al as ka n at iv e, n at iv e ha wa iia n/ ot he r p ac ifi c isl an de r p at ie n ts , % 63.9% 83.3% 65.6% 53.7% 80.0% a. b. 36.9% 64.0% 76.5% 82.8% c. 0 10 20 30 40 50 60 70 80 90 100 p at ie n ts , % 0 10 20 30 40 50 60 70 80 90 100 p at ie n ts , % otc, over the counter; tnfi, tumor necrosis factor inhibitor. figure 5. views on a new once-daily oral treatment, by treatment group 0 10 20 30 40 50 60 70 80 90 100 p at ie n ts , % yes neither yes nor no no yes neither yes nor no no yes neither yes nor no no yes neither yes nor no no yes no less interference with daily life (p < 0.001) convenience of treatment (p = 0.094) less anxiety than with injection/infusion (p = 0.041) reduction in symptoms compared with current treatment (p < 0.001) intent to start new oral psoriasis treatment (p < 0.001) apremilast (n = 344) tnfi (n = 242) ustekinumab (n = 98) topical therapy/phototherapy (n = 98) tnfi, tumor necrosis factor inhibitor. • only treatment group, race/ethnicity, and psoriasis severity were statistically significant factors in the model • the following responses were examined for intent to start a new once-daily oral treatment (yes/no), by selected categories: — 83% of black respondents would start the new once-daily oral treatment • compared with white patients, the odds ratio (or) of intent to start the new treatment was 2.4 (95% confidence interval [ci], 1.4–4.2) among black respondents (p = 0.036) — intent to start the new once-daily oral treatment increased with psoriasis severity over the past week, with 76.5% of respondents with moderate psoriasis and 82.8% of respondents with severe disease answering “yes” • compared with patients with no psoriasis symptoms or signs over the past week, the or of intent to start the new treatment was 3.2 (95% ci, 2.0–4.9) among patients with mild psoriasis, 5.0 (95% ci, 3.1–8.2) among patients with moderate psoriasis, and 7.6 (95% ci, 3.9–15.0) among patients with severe psoriasis; all p < 0.001 — 79.6% of patients who responded that the new once-daily oral treatment would cause them less anxiety than an injection would start the new treatment — 87.6% of respondents who believed that the new once-daily oral treatment would reduce their symptoms more than their current treatment would start the new treatment • asked to rank characteristics of psoriasis treatment in order of importance, 58.3% of respondents ranked “extent of skin clearance” as first or second, while 43.7% ranked “route of administration” as first or second (figure 6) • laboratory monitoring was ranked least important by more than half (53.0%) of the patients figure 6. reason for treatment choice ranking 37.1 22.8 17.0 11.9 10.0 1.3 21.2 20.9 15.0 20.3 19.1 3.5 22.1 18.6 15.5 20.2 18.0 5.6 12.2 19.1 22.3 19.8 14.7 11.8 5.9 12.4 21.3 19.5 16.0 24.9 1.5 6.2 8.8 8.3 22.2 53.0 0 10 20 30 40 50 60 sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g rank 1 (p < 0.001) rank 2 (p = 0.005) rank 3 (p = 0.030) rank 4 (p = 0.233) rank 5 (p = 0.005) rank 6 (p < 0.001) p at ie n ts , % conclusions • this large, real-world study provided an account of how psoriasis impacts patients’ lives and treatment choices • patients with severe disease, black patients, and patients receiving injectable treatments were more likely to choose the new oral treatment compared with patients with mild disease, white patients, and patients receiving apremilast, respectively • willingness to start the new psoriasis treatment was common among all treatment groups • the new treatment was viewed as causing less anxiety compared with injectables across all treatment groups • extent of skin clearance and route of administration were reported as the top-ranked reasons for patients' psoriasis treatment choice • consideration of the treatment characteristics that drive the decision-making of patients with psoriasis is crucial for making effective treatment recommendations in clinical practice reference 1. feldman sr, et al. j health econ outcomes res. 2016;4:141-157. acknowledgments • this study was sponsored by bristol myers squibb • medical writing and editorial assistance was provided by tulika bhushan bahukhandi, rph, ms, of peloton advantage, llc, an open health company, and funded by bristol myers squibb disclosures • awa: has served as a research investigator, scientific advisor, and/or speaker for abbvie, almirall, arcutis biotherapeutics, aslan, beiersdorf, boehringer ingelheim/parexel, bristol myers squibb, dermavant, dermira, eli lilly, epi, incyte, leo, janssen, nimbus, novartis, ortho dermatologics, pfizer, sanofi genzyme, sun, regeneron, and ucb • ls, dd, sk, and vp: employees of and may own stock options in bristol myers squibb • nj, sr, sj, and dp: employees of open health, which received consulting fees from bristol myers squibb • dw and kb: employees of rti health solutions, which received consulting fees from bristol myers squibb scientific content on demand to request a copy of this poster: scan qr code via a barcode reader application qr codes are valid for 30 days after the congress presentation date. evaluating treatment choice among patients with moderate or severe psoriasis in the united states april w. armstrong,1 sayeli jayade,2 sanika rege,2 namita joshi,2 vardhaman patel,3 david davidson,3 samaneh kalirai,3 daniel wolin,4 kimberly boyle,4 dipen patel,2 lauren seigel3 1keck school of medicine, university of southern california, los angeles, ca; 2open health, bethesda, md; 3bristol myers squibb, princeton, nj; 4rti health solutions, research triangle park, nc presented at the 2022 fall clinical dermatology conference; october 20–23, 2022; las vegas, nv this poster may not be reproduced without written permission from the authors.email for april w. armstrong, md, mph: aprilarmstrong@post.harvard.edu synopsis • while several psoriasis treatments are available and in development, different treatment modalities are associated with varying effectiveness, risks, and economic burden, and these factors are likely to influence patients’ decisions related to their psoriasis treatment1 • this study explored the element of treatment decision-making driven by patient experiences — a cross-sectional, web-based survey captured the demographic and clinical characteristics, treatment attributes affecting therapeutic decisions, and perceptions of a new, hypothetical, once-daily oral psoriasis treatment (deucravacitinib) among patients with moderate to severe plaque psoriasis • understanding the factors that drive patients’ treatment preference is crucial for guiding clinical decision-making objectives primary • to identify factors associated with the choice of a new once-daily oral psoriasis treatment with efficacy superior to that of existing oral therapies in patients with moderate to severe psoriasis currently receiving apremilast, tumor necrosis factor inhibitors (tnfis), ustekinumab, topicals, or nonprescription treatments secondary • to rank the importance of treatment attributes to patients with moderate to severe psoriasis using apremilast, tnfis, ustekinumab, topicals, or nonprescription treatments • to elicit views on a new once-daily oral psoriasis treatment among patients with moderate to severe psoriasis using apremilast, tnfis, ustekinumab, topicals, or nonprescription treatments target product profile (deucravacitinib) • tablet formulation with once-daily dosing • clinical studies showed: — 53% of patients reported clear/mostly clear skin within 4 months — 83% of patients who reported a 75% reduction in psoriasis severity maintained this improvement at 1 year — non-serious adverse events, such as cold-like symptoms, headache, diarrhea, nausea, rash, and risk of herpes infection, led to few discontinuations • regular laboratory monitoring is not required, although pre-initiation testing may be needed • out-of-pocket costs may be similar to those of the alternative psoriasis treatments in consideration methods • a cross-sectional, web-based survey of the demographics and clinical characteristics of patients with psoriasis, their views on treatment characteristics that affect treatment-related decisions, and their perceptions of a new, hypothetical, once-daily oral psoriasis treatment • patients were assigned to predefined treatment groups: apremilast, a tnfi, ustekinumab, a topical therapy/phototherapy, and over-the-counter (otc) treatments or no treatment, based on their self-reported current treatment at the time of the survey • a hypothetical psoriasis treatment profile, described by dosage, efficacy, adverse effects, and out-of-pocket costs, was shown to the patients to elicit their views on: (1) interference with everyday life, (2) convenience, (3) treatment-related anxiety, and likelihood of initiating treatment, both (4) without a safety warning and (5) with a safety warning inclusion criteria • ≥18 years of age • residing in the united states • able to read and understand english • physician-diagnosed (self-reported) moderate or severe plaque psoriasis exclusion criteria • mild psoriasis • lack of online consent for the web-based survey data collection process • the study was reviewed and approved by an institutional review board • the study used a convenience sample of patients with moderate or severe psoriasis who were recruited by global perspectives to collect patient-reported data • patients were asked to complete an electronic patient survey that included questions from patient-reported outcome (pro) instruments and de novo questions • potential survey participants were provided with a link to the survey and completed screening questions to determine eligibility, followed by an informed consent checkbox • the final survey was administered to 882 patients statistical analysis • stepwise multivariable logistic regression was conducted to determine sociodemographic and clinical characteristics associated with the choice of the new treatment among patients who were currently receiving treatment or who had never received treatment — independent variables: treatment group, age, sex, race/ethnicity, psoriasis severity over the past week, comorbidities, disease and treatment duration, presence of psoriatic arthritis (psa) at baseline, number of flares, and number of body regions affected • treatment attributes (route of administration, extent of skin clearance, laboratory monitoring, durability, safety, and dosing frequency) were ranked as an ordinal category (scale of 1–6) by patients • chi-square test was conducted to detect significant differences between patient rankings of each treatment attribute and to assess the variations in patient views on the new oral treatment results • figure 1 shows the responses of the 5 baseline treatment groups surveyed • the study sample included 882 patients (mean age = 45.7 [±12.8] years); the majority were female (67.7%), most were white (74.9%), and their average duration of time since psoriasis diagnosis was 14.9 (±11.8) years (figures 2 and 3; table 1) • of 882 patients, 818 (92.8%) were currently receiving treatment and had been on their current treatment for a mean of 2.9 (±4.8) years (table 2) • with their current treatment regimen, 50.8% of patients in the total study population described their psoriasis over the past week as mild, very mild, or none, while 36.5% reported it as moderate and 12.7% reported it as severe or very severe (table 2) figure 1. targeted baseline treatment groups 344 242 98 98 100 0 50 100 150 200 250 300 350 400 p at ie n ts w h o c o m p le te d s u rv e y, n treatment group group 1: apremilast group 2: tnfi group 3: ustekinumab group 4: topical/phototherapy group 5: exploratorya athe exploratory group included patients who were using nonprescription treatments (n = 36), patients who had never received treatment (n = 17), and patients who had received treatment in the past but were not currently receiving treatment (n = 47). tnfi, tumor necrosis factor inhibitor. figure 2. key baseline characteristics, by sex (a) and race/ethnicitya (b) 74.9% 14.1% 2% 2% 0.2% 2.4% 6.1% white black american indian/ alaska native asian native hawaiian/ other pacific islander other preferred not to answer b.a. male female preferred not to answer 32.0% 67.7% 0.3% apercentages sum to >100% because respondents could select multiple races/ethnicities, as applicable. figure 3. key baseline characteristics for all respondents by insurance typea 13.6% 11.9% 54.5% 21.1% 2.2% 3.4% medicare medicaid employer-sponsored private insurance individually purchased private insurance uninsured military/veterans' coverage apercentages sum to >100% because respondents could select more than 1 insurance type, as applicable. table 1. key baseline characteristics for all respondents by patient age category all respondents (n = 882) mean 45.71 median (q1–q3) 45 range 18–76 q1–q3, quartiles 1–3. table 2. key baseline clinical characteristics parameter statistic or category all respondents, n = 882 (%) treatment status, n (%) currently receiving treatment 818 (92.8) was receiving treatment but has stopped 47 (5.3) never received treatment 17 (1.9) treatment duration, years mean (sd) 2.86 (4.81) median (q1–q3) 1.0 (0.0–3.0) range 0.0–42.0 current treatment type, n (%) over-the-counter nonprescription 225 (27.5) topical prescription steroid 230 (28.1) topical vitamin d analog 49 (6.0) other topical treatment 55 (6.7) ultraviolet light/phototherapy 51 (6.2) apremilast 356 (43.5) ustekinumab 101 (12.3) tnfi treatment 251 (30.7) psoriasis severity over the past week, n (%) none 31 (14.8) very mild 155 (17.6) mild 162 (18.4) moderate 322 (36.5) severe 86 (9.8) very severe 26 (2.9) bsa, body surface area; q1–q3, quartiles 1–3; sd, standard deviation; tnfi, tumor necrosis factor inhibitor. • among patients who were currently receiving treatment or who had never received treatment (n = 835), apremilast (41.2%) and tnfis (29.0%) were the most commonly used treatments, and otc or no treatment was the least common group (6.3%) (table 3) • of patients who had never received treatment, 88.2% expressed intent to start the new oral psoriasis treatment, compared with 80.6% of patients who used nonprescription otc treatment, 75.5% of patients who used ustekinumab, 74.0% of patients who used a tnfi, 69.4% of patients who used topical therapy, and 55.2% of patients who used apremilast (figure 4) • willingness to start the new, once-daily oral treatment was high across all groups, including patients currently using apremilast • in response to questions about the new treatment, 83.7% reported that it would be convenient, 65.0% reported that it would cause less anxiety than an injection or infusion, 55.3% reported that it would interfere less with their everyday life, and 50.2% reported that it would reduce their symptoms more than their current psoriasis treatment (figure 5) table 3. intent to start a new once-daily oral psoriasis treatment variable category intent to start new treatment all, n = 835 (%) yes, n = 555 (%) no, n = 280 (%) treatment group apremilast 344 (41.2) 190 (34.2) 154 (55.0) tnfi 242 (29.0) 179 (32.3) 63 (22.5) ustekinumab 98 (11.7) 74 (13.3) 24 (8.6) topical therapy 98 (11.7) 68 (12.3) 30 (10.7) otc or no treatment 53 (6.3) 44 (7.9) 9 (3.2) race/ethnicity white 610 (73.1) 390 (70.3) 220 (78.6) black 114 (13.7) 95 (17.1) 19 (6.8) asian, american indian/alaska native, native hawaiian/other pacifi c islander 32 (3.8) 21 (3.8) 11 (3.9) preferred not to answer 54 (6.5) 29 (5.2) 25 (8.9) other 25 (3.0) 20 (3.6) 5 (1.8) psoriasis severity over the past week (based on a 6-point scale) none 130 (15.6) 48 (8.6) 82 (29.3) mild 308 (36.9) 197 (35.5) 111 (39.6) moderate 298 (35.7) 228 (41.1) 70 (25.0) severe 99 (11.9) 82 (14.8) 17 (6.1) otc, over the counter; tnfi, tumor necrosis factor inhibitor. figure 4. intent to start a new once-daily oral treatment, by treatment group (a), race/ ethnicity (b), and psoriasis severity over the past week (c), all p < 0.001 55.2% 74.0% 75.5% 69.4% 83.0% 0 10 20 30 40 50 60 70 80 90 100 ap re m ila st tn fi us te ki nu m ab to pi ca l t he ra py w hi te bl ac k pr ef er re d no t to a ns we r ot he r no ne mi ld mo de ra te se ve re ot c or n o tr ea tm en t as ia n, a m er ic an in di an / al as ka n at iv e, n at iv e ha wa iia n/ ot he r p ac ifi c isl an de r p at ie n ts , % 63.9% 83.3% 65.6% 53.7% 80.0% a. b. 36.9% 64.0% 76.5% 82.8% c. 0 10 20 30 40 50 60 70 80 90 100 p at ie n ts , % 0 10 20 30 40 50 60 70 80 90 100 p at ie n ts , % otc, over the counter; tnfi, tumor necrosis factor inhibitor. figure 5. views on a new once-daily oral treatment, by treatment group 0 10 20 30 40 50 60 70 80 90 100 p at ie n ts , % yes neither yes nor no no yes neither yes nor no no yes neither yes nor no no yes neither yes nor no no yes no less interference with daily life (p < 0.001) convenience of treatment (p = 0.094) less anxiety than with injection/infusion (p = 0.041) reduction in symptoms compared with current treatment (p < 0.001) intent to start new oral psoriasis treatment (p < 0.001) apremilast (n = 344) tnfi (n = 242) ustekinumab (n = 98) topical therapy/phototherapy (n = 98) tnfi, tumor necrosis factor inhibitor. • only treatment group, race/ethnicity, and psoriasis severity were statistically significant factors in the model • the following responses were examined for intent to start a new once-daily oral treatment (yes/no), by selected categories: — 83% of black respondents would start the new once-daily oral treatment • compared with white patients, the odds ratio (or) of intent to start the new treatment was 2.4 (95% confidence interval [ci], 1.4–4.2) among black respondents (p = 0.036) — intent to start the new once-daily oral treatment increased with psoriasis severity over the past week, with 76.5% of respondents with moderate psoriasis and 82.8% of respondents with severe disease answering “yes” • compared with patients with no psoriasis symptoms or signs over the past week, the or of intent to start the new treatment was 3.2 (95% ci, 2.0–4.9) among patients with mild psoriasis, 5.0 (95% ci, 3.1–8.2) among patients with moderate psoriasis, and 7.6 (95% ci, 3.9–15.0) among patients with severe psoriasis; all p < 0.001 — 79.6% of patients who responded that the new once-daily oral treatment would cause them less anxiety than an injection would start the new treatment — 87.6% of respondents who believed that the new once-daily oral treatment would reduce their symptoms more than their current treatment would start the new treatment • asked to rank characteristics of psoriasis treatment in order of importance, 58.3% of respondents ranked “extent of skin clearance” as first or second, while 43.7% ranked “route of administration” as first or second (figure 6) • laboratory monitoring was ranked least important by more than half (53.0%) of the patients figure 6. reason for treatment choice ranking 37.1 22.8 17.0 11.9 10.0 1.3 21.2 20.9 15.0 20.3 19.1 3.5 22.1 18.6 15.5 20.2 18.0 5.6 12.2 19.1 22.3 19.8 14.7 11.8 5.9 12.4 21.3 19.5 16.0 24.9 1.5 6.2 8.8 8.3 22.2 53.0 0 10 20 30 40 50 60 sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g rank 1 (p < 0.001) rank 2 (p = 0.005) rank 3 (p = 0.030) rank 4 (p = 0.233) rank 5 (p = 0.005) rank 6 (p < 0.001) p at ie n ts , % conclusions • this large, real-world study provided an account of how psoriasis impacts patients’ lives and treatment choices • patients with severe disease, black patients, and patients receiving injectable treatments were more likely to choose the new oral treatment compared with patients with mild disease, white patients, and patients receiving apremilast, respectively • willingness to start the new psoriasis treatment was common among all treatment groups • the new treatment was viewed as causing less anxiety compared with injectables across all treatment groups • extent of skin clearance and route of administration were reported as the top-ranked reasons for patients' psoriasis treatment choice • consideration of the treatment characteristics that drive the decision-making of patients with psoriasis is crucial for making effective treatment recommendations in clinical practice reference 1. feldman sr, et al. j health econ outcomes res. 2016;4:141-157. acknowledgments • this study was sponsored by bristol myers squibb • medical writing and editorial assistance was provided by tulika bhushan bahukhandi, rph, ms, of peloton advantage, llc, an open health company, and funded by bristol myers squibb disclosures • awa: has served as a research investigator, scientific advisor, and/or speaker for abbvie, almirall, arcutis biotherapeutics, aslan, beiersdorf, boehringer ingelheim/parexel, bristol myers squibb, dermavant, dermira, eli lilly, epi, incyte, leo, janssen, nimbus, novartis, ortho dermatologics, pfizer, sanofi genzyme, sun, regeneron, and ucb • ls, dd, sk, and vp: employees of and may own stock options in bristol myers squibb • nj, sr, sj, and dp: employees of open health, which received consulting fees from bristol myers squibb • dw and kb: employees of rti health solutions, which received consulting fees from bristol myers squibb scientific content on demand to request a copy of this poster: scan qr code via a barcode reader application qr codes are valid for 30 days after the congress presentation date. evaluating treatment choice among patients with moderate or severe psoriasis in the united states april w. armstrong,1 sayeli jayade,2 sanika rege,2 namita joshi,2 vardhaman patel,3 david davidson,3 samaneh kalirai,3 daniel wolin,4 kimberly boyle,4 dipen patel,2 lauren seigel3 1keck school of medicine, university of southern california, los angeles, ca; 2open health, bethesda, md; 3bristol myers squibb, princeton, nj; 4rti health solutions, research triangle park, nc presented at the 2022 fall clinical dermatology conference; october 20–23, 2022; las vegas, nv this poster may not be reproduced without written permission from the authors.email for april w. armstrong, md, mph: aprilarmstrong@post.harvard.edu synopsis • while several psoriasis treatments are available and in development, different treatment modalities are associated with varying effectiveness, risks, and economic burden, and these factors are likely to influence patients’ decisions related to their psoriasis treatment1 • this study explored the element of treatment decision-making driven by patient experiences — a cross-sectional, web-based survey captured the demographic and clinical characteristics, treatment attributes affecting therapeutic decisions, and perceptions of a new, hypothetical, once-daily oral psoriasis treatment (deucravacitinib) among patients with moderate to severe plaque psoriasis • understanding the factors that drive patients’ treatment preference is crucial for guiding clinical decision-making objectives primary • to identify factors associated with the choice of a new once-daily oral psoriasis treatment with efficacy superior to that of existing oral therapies in patients with moderate to severe psoriasis currently receiving apremilast, tumor necrosis factor inhibitors (tnfis), ustekinumab, topicals, or nonprescription treatments secondary • to rank the importance of treatment attributes to patients with moderate to severe psoriasis using apremilast, tnfis, ustekinumab, topicals, or nonprescription treatments • to elicit views on a new once-daily oral psoriasis treatment among patients with moderate to severe psoriasis using apremilast, tnfis, ustekinumab, topicals, or nonprescription treatments target product profile (deucravacitinib) • tablet formulation with once-daily dosing • clinical studies showed: — 53% of patients reported clear/mostly clear skin within 4 months — 83% of patients who reported a 75% reduction in psoriasis severity maintained this improvement at 1 year — non-serious adverse events, such as cold-like symptoms, headache, diarrhea, nausea, rash, and risk of herpes infection, led to few discontinuations • regular laboratory monitoring is not required, although pre-initiation testing may be needed • out-of-pocket costs may be similar to those of the alternative psoriasis treatments in consideration methods • a cross-sectional, web-based survey of the demographics and clinical characteristics of patients with psoriasis, their views on treatment characteristics that affect treatment-related decisions, and their perceptions of a new, hypothetical, once-daily oral psoriasis treatment • patients were assigned to predefined treatment groups: apremilast, a tnfi, ustekinumab, a topical therapy/phototherapy, and over-the-counter (otc) treatments or no treatment, based on their self-reported current treatment at the time of the survey • a hypothetical psoriasis treatment profile, described by dosage, efficacy, adverse effects, and out-of-pocket costs, was shown to the patients to elicit their views on: (1) interference with everyday life, (2) convenience, (3) treatment-related anxiety, and likelihood of initiating treatment, both (4) without a safety warning and (5) with a safety warning inclusion criteria • ≥18 years of age • residing in the united states • able to read and understand english • physician-diagnosed (self-reported) moderate or severe plaque psoriasis exclusion criteria • mild psoriasis • lack of online consent for the web-based survey data collection process • the study was reviewed and approved by an institutional review board • the study used a convenience sample of patients with moderate or severe psoriasis who were recruited by global perspectives to collect patient-reported data • patients were asked to complete an electronic patient survey that included questions from patient-reported outcome (pro) instruments and de novo questions • potential survey participants were provided with a link to the survey and completed screening questions to determine eligibility, followed by an informed consent checkbox • the final survey was administered to 882 patients statistical analysis • stepwise multivariable logistic regression was conducted to determine sociodemographic and clinical characteristics associated with the choice of the new treatment among patients who were currently receiving treatment or who had never received treatment — independent variables: treatment group, age, sex, race/ethnicity, psoriasis severity over the past week, comorbidities, disease and treatment duration, presence of psoriatic arthritis (psa) at baseline, number of flares, and number of body regions affected • treatment attributes (route of administration, extent of skin clearance, laboratory monitoring, durability, safety, and dosing frequency) were ranked as an ordinal category (scale of 1–6) by patients • chi-square test was conducted to detect significant differences between patient rankings of each treatment attribute and to assess the variations in patient views on the new oral treatment results • figure 1 shows the responses of the 5 baseline treatment groups surveyed • the study sample included 882 patients (mean age = 45.7 [±12.8] years); the majority were female (67.7%), most were white (74.9%), and their average duration of time since psoriasis diagnosis was 14.9 (±11.8) years (figures 2 and 3; table 1) • of 882 patients, 818 (92.8%) were currently receiving treatment and had been on their current treatment for a mean of 2.9 (±4.8) years (table 2) • with their current treatment regimen, 50.8% of patients in the total study population described their psoriasis over the past week as mild, very mild, or none, while 36.5% reported it as moderate and 12.7% reported it as severe or very severe (table 2) figure 1. targeted baseline treatment groups 344 242 98 98 100 0 50 100 150 200 250 300 350 400 p at ie n ts w h o c o m p le te d s u rv e y, n treatment group group 1: apremilast group 2: tnfi group 3: ustekinumab group 4: topical/phototherapy group 5: exploratorya athe exploratory group included patients who were using nonprescription treatments (n = 36), patients who had never received treatment (n = 17), and patients who had received treatment in the past but were not currently receiving treatment (n = 47). tnfi, tumor necrosis factor inhibitor. figure 2. key baseline characteristics, by sex (a) and race/ethnicitya (b) 74.9% 14.1% 2% 2% 0.2% 2.4% 6.1% white black american indian/ alaska native asian native hawaiian/ other pacific islander other preferred not to answer b.a. male female preferred not to answer 32.0% 67.7% 0.3% apercentages sum to >100% because respondents could select multiple races/ethnicities, as applicable. figure 3. key baseline characteristics for all respondents by insurance typea 13.6% 11.9% 54.5% 21.1% 2.2% 3.4% medicare medicaid employer-sponsored private insurance individually purchased private insurance uninsured military/veterans' coverage apercentages sum to >100% because respondents could select more than 1 insurance type, as applicable. table 1. key baseline characteristics for all respondents by patient age category all respondents (n = 882) mean 45.71 median (q1–q3) 45 range 18–76 q1–q3, quartiles 1–3. table 2. key baseline clinical characteristics parameter statistic or category all respondents, n = 882 (%) treatment status, n (%) currently receiving treatment 818 (92.8) was receiving treatment but has stopped 47 (5.3) never received treatment 17 (1.9) treatment duration, years mean (sd) 2.86 (4.81) median (q1–q3) 1.0 (0.0–3.0) range 0.0–42.0 current treatment type, n (%) over-the-counter nonprescription 225 (27.5) topical prescription steroid 230 (28.1) topical vitamin d analog 49 (6.0) other topical treatment 55 (6.7) ultraviolet light/phototherapy 51 (6.2) apremilast 356 (43.5) ustekinumab 101 (12.3) tnfi treatment 251 (30.7) psoriasis severity over the past week, n (%) none 31 (14.8) very mild 155 (17.6) mild 162 (18.4) moderate 322 (36.5) severe 86 (9.8) very severe 26 (2.9) bsa, body surface area; q1–q3, quartiles 1–3; sd, standard deviation; tnfi, tumor necrosis factor inhibitor. • among patients who were currently receiving treatment or who had never received treatment (n = 835), apremilast (41.2%) and tnfis (29.0%) were the most commonly used treatments, and otc or no treatment was the least common group (6.3%) (table 3) • of patients who had never received treatment, 88.2% expressed intent to start the new oral psoriasis treatment, compared with 80.6% of patients who used nonprescription otc treatment, 75.5% of patients who used ustekinumab, 74.0% of patients who used a tnfi, 69.4% of patients who used topical therapy, and 55.2% of patients who used apremilast (figure 4) • willingness to start the new, once-daily oral treatment was high across all groups, including patients currently using apremilast • in response to questions about the new treatment, 83.7% reported that it would be convenient, 65.0% reported that it would cause less anxiety than an injection or infusion, 55.3% reported that it would interfere less with their everyday life, and 50.2% reported that it would reduce their symptoms more than their current psoriasis treatment (figure 5) table 3. intent to start a new once-daily oral psoriasis treatment variable category intent to start new treatment all, n = 835 (%) yes, n = 555 (%) no, n = 280 (%) treatment group apremilast 344 (41.2) 190 (34.2) 154 (55.0) tnfi 242 (29.0) 179 (32.3) 63 (22.5) ustekinumab 98 (11.7) 74 (13.3) 24 (8.6) topical therapy 98 (11.7) 68 (12.3) 30 (10.7) otc or no treatment 53 (6.3) 44 (7.9) 9 (3.2) race/ethnicity white 610 (73.1) 390 (70.3) 220 (78.6) black 114 (13.7) 95 (17.1) 19 (6.8) asian, american indian/alaska native, native hawaiian/other pacifi c islander 32 (3.8) 21 (3.8) 11 (3.9) preferred not to answer 54 (6.5) 29 (5.2) 25 (8.9) other 25 (3.0) 20 (3.6) 5 (1.8) psoriasis severity over the past week (based on a 6-point scale) none 130 (15.6) 48 (8.6) 82 (29.3) mild 308 (36.9) 197 (35.5) 111 (39.6) moderate 298 (35.7) 228 (41.1) 70 (25.0) severe 99 (11.9) 82 (14.8) 17 (6.1) otc, over the counter; tnfi, tumor necrosis factor inhibitor. figure 4. intent to start a new once-daily oral treatment, by treatment group (a), race/ ethnicity (b), and psoriasis severity over the past week (c), all p < 0.001 55.2% 74.0% 75.5% 69.4% 83.0% 0 10 20 30 40 50 60 70 80 90 100 ap re m ila st tn fi us te ki nu m ab to pi ca l t he ra py w hi te bl ac k pr ef er re d no t to a ns we r ot he r no ne mi ld mo de ra te se ve re ot c or n o tr ea tm en t as ia n, a m er ic an in di an / al as ka n at iv e, n at iv e ha wa iia n/ ot he r p ac ifi c isl an de r p at ie n ts , % 63.9% 83.3% 65.6% 53.7% 80.0% a. b. 36.9% 64.0% 76.5% 82.8% c. 0 10 20 30 40 50 60 70 80 90 100 p at ie n ts , % 0 10 20 30 40 50 60 70 80 90 100 p at ie n ts , % otc, over the counter; tnfi, tumor necrosis factor inhibitor. figure 5. views on a new once-daily oral treatment, by treatment group 0 10 20 30 40 50 60 70 80 90 100 p at ie n ts , % yes neither yes nor no no yes neither yes nor no no yes neither yes nor no no yes neither yes nor no no yes no less interference with daily life (p < 0.001) convenience of treatment (p = 0.094) less anxiety than with injection/infusion (p = 0.041) reduction in symptoms compared with current treatment (p < 0.001) intent to start new oral psoriasis treatment (p < 0.001) apremilast (n = 344) tnfi (n = 242) ustekinumab (n = 98) topical therapy/phototherapy (n = 98) tnfi, tumor necrosis factor inhibitor. • only treatment group, race/ethnicity, and psoriasis severity were statistically significant factors in the model • the following responses were examined for intent to start a new once-daily oral treatment (yes/no), by selected categories: — 83% of black respondents would start the new once-daily oral treatment • compared with white patients, the odds ratio (or) of intent to start the new treatment was 2.4 (95% confidence interval [ci], 1.4–4.2) among black respondents (p = 0.036) — intent to start the new once-daily oral treatment increased with psoriasis severity over the past week, with 76.5% of respondents with moderate psoriasis and 82.8% of respondents with severe disease answering “yes” • compared with patients with no psoriasis symptoms or signs over the past week, the or of intent to start the new treatment was 3.2 (95% ci, 2.0–4.9) among patients with mild psoriasis, 5.0 (95% ci, 3.1–8.2) among patients with moderate psoriasis, and 7.6 (95% ci, 3.9–15.0) among patients with severe psoriasis; all p < 0.001 — 79.6% of patients who responded that the new once-daily oral treatment would cause them less anxiety than an injection would start the new treatment — 87.6% of respondents who believed that the new once-daily oral treatment would reduce their symptoms more than their current treatment would start the new treatment • asked to rank characteristics of psoriasis treatment in order of importance, 58.3% of respondents ranked “extent of skin clearance” as first or second, while 43.7% ranked “route of administration” as first or second (figure 6) • laboratory monitoring was ranked least important by more than half (53.0%) of the patients figure 6. reason for treatment choice ranking 37.1 22.8 17.0 11.9 10.0 1.3 21.2 20.9 15.0 20.3 19.1 3.5 22.1 18.6 15.5 20.2 18.0 5.6 12.2 19.1 22.3 19.8 14.7 11.8 5.9 12.4 21.3 19.5 16.0 24.9 1.5 6.2 8.8 8.3 22.2 53.0 0 10 20 30 40 50 60 sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g rank 1 (p < 0.001) rank 2 (p = 0.005) rank 3 (p = 0.030) rank 4 (p = 0.233) rank 5 (p = 0.005) rank 6 (p < 0.001) p at ie n ts , % conclusions • this large, real-world study provided an account of how psoriasis impacts patients’ lives and treatment choices • patients with severe disease, black patients, and patients receiving injectable treatments were more likely to choose the new oral treatment compared with patients with mild disease, white patients, and patients receiving apremilast, respectively • willingness to start the new psoriasis treatment was common among all treatment groups • the new treatment was viewed as causing less anxiety compared with injectables across all treatment groups • extent of skin clearance and route of administration were reported as the top-ranked reasons for patients' psoriasis treatment choice • consideration of the treatment characteristics that drive the decision-making of patients with psoriasis is crucial for making effective treatment recommendations in clinical practice reference 1. feldman sr, et al. j health econ outcomes res. 2016;4:141-157. acknowledgments • this study was sponsored by bristol myers squibb • medical writing and editorial assistance was provided by tulika bhushan bahukhandi, rph, ms, of peloton advantage, llc, an open health company, and funded by bristol myers squibb disclosures • awa: has served as a research investigator, scientific advisor, and/or speaker for abbvie, almirall, arcutis biotherapeutics, aslan, beiersdorf, boehringer ingelheim/parexel, bristol myers squibb, dermavant, dermira, eli lilly, epi, incyte, leo, janssen, nimbus, novartis, ortho dermatologics, pfizer, sanofi genzyme, sun, regeneron, and ucb • ls, dd, sk, and vp: employees of and may own stock options in bristol myers squibb • nj, sr, sj, and dp: employees of open health, which received consulting fees from bristol myers squibb • dw and kb: employees of rti health solutions, which received consulting fees from bristol myers squibb scientific content on demand to request a copy of this poster: scan qr code via a barcode reader application qr codes are valid for 30 days after the congress presentation date. evaluating treatment choice among patients with moderate or severe psoriasis in the united states april w. armstrong,1 sayeli jayade,2 sanika rege,2 namita joshi,2 vardhaman patel,3 david davidson,3 samaneh kalirai,3 daniel wolin,4 kimberly boyle,4 dipen patel,2 lauren seigel3 1keck school of medicine, university of southern california, los angeles, ca; 2open health, bethesda, md; 3bristol myers squibb, princeton, nj; 4rti health solutions, research triangle park, nc presented at the 2022 fall clinical dermatology conference; october 20–23, 2022; las vegas, nv this poster may not be reproduced without written permission from the authors.email for april w. armstrong, md, mph: aprilarmstrong@post.harvard.edu synopsis • while several psoriasis treatments are available and in development, different treatment modalities are associated with varying effectiveness, risks, and economic burden, and these factors are likely to influence patients’ decisions related to their psoriasis treatment1 • this study explored the element of treatment decision-making driven by patient experiences — a cross-sectional, web-based survey captured the demographic and clinical characteristics, treatment attributes affecting therapeutic decisions, and perceptions of a new, hypothetical, once-daily oral psoriasis treatment (deucravacitinib) among patients with moderate to severe plaque psoriasis • understanding the factors that drive patients’ treatment preference is crucial for guiding clinical decision-making objectives primary • to identify factors associated with the choice of a new once-daily oral psoriasis treatment with efficacy superior to that of existing oral therapies in patients with moderate to severe psoriasis currently receiving apremilast, tumor necrosis factor inhibitors (tnfis), ustekinumab, topicals, or nonprescription treatments secondary • to rank the importance of treatment attributes to patients with moderate to severe psoriasis using apremilast, tnfis, ustekinumab, topicals, or nonprescription treatments • to elicit views on a new once-daily oral psoriasis treatment among patients with moderate to severe psoriasis using apremilast, tnfis, ustekinumab, topicals, or nonprescription treatments target product profile (deucravacitinib) • tablet formulation with once-daily dosing • clinical studies showed: — 53% of patients reported clear/mostly clear skin within 4 months — 83% of patients who reported a 75% reduction in psoriasis severity maintained this improvement at 1 year — non-serious adverse events, such as cold-like symptoms, headache, diarrhea, nausea, rash, and risk of herpes infection, led to few discontinuations • regular laboratory monitoring is not required, although pre-initiation testing may be needed • out-of-pocket costs may be similar to those of the alternative psoriasis treatments in consideration methods • a cross-sectional, web-based survey of the demographics and clinical characteristics of patients with psoriasis, their views on treatment characteristics that affect treatment-related decisions, and their perceptions of a new, hypothetical, once-daily oral psoriasis treatment • patients were assigned to predefined treatment groups: apremilast, a tnfi, ustekinumab, a topical therapy/phototherapy, and over-the-counter (otc) treatments or no treatment, based on their self-reported current treatment at the time of the survey • a hypothetical psoriasis treatment profile, described by dosage, efficacy, adverse effects, and out-of-pocket costs, was shown to the patients to elicit their views on: (1) interference with everyday life, (2) convenience, (3) treatment-related anxiety, and likelihood of initiating treatment, both (4) without a safety warning and (5) with a safety warning inclusion criteria • ≥18 years of age • residing in the united states • able to read and understand english • physician-diagnosed (self-reported) moderate or severe plaque psoriasis exclusion criteria • mild psoriasis • lack of online consent for the web-based survey data collection process • the study was reviewed and approved by an institutional review board • the study used a convenience sample of patients with moderate or severe psoriasis who were recruited by global perspectives to collect patient-reported data • patients were asked to complete an electronic patient survey that included questions from patient-reported outcome (pro) instruments and de novo questions • potential survey participants were provided with a link to the survey and completed screening questions to determine eligibility, followed by an informed consent checkbox • the final survey was administered to 882 patients statistical analysis • stepwise multivariable logistic regression was conducted to determine sociodemographic and clinical characteristics associated with the choice of the new treatment among patients who were currently receiving treatment or who had never received treatment — independent variables: treatment group, age, sex, race/ethnicity, psoriasis severity over the past week, comorbidities, disease and treatment duration, presence of psoriatic arthritis (psa) at baseline, number of flares, and number of body regions affected • treatment attributes (route of administration, extent of skin clearance, laboratory monitoring, durability, safety, and dosing frequency) were ranked as an ordinal category (scale of 1–6) by patients • chi-square test was conducted to detect significant differences between patient rankings of each treatment attribute and to assess the variations in patient views on the new oral treatment results • figure 1 shows the responses of the 5 baseline treatment groups surveyed • the study sample included 882 patients (mean age = 45.7 [±12.8] years); the majority were female (67.7%), most were white (74.9%), and their average duration of time since psoriasis diagnosis was 14.9 (±11.8) years (figures 2 and 3; table 1) • of 882 patients, 818 (92.8%) were currently receiving treatment and had been on their current treatment for a mean of 2.9 (±4.8) years (table 2) • with their current treatment regimen, 50.8% of patients in the total study population described their psoriasis over the past week as mild, very mild, or none, while 36.5% reported it as moderate and 12.7% reported it as severe or very severe (table 2) figure 1. targeted baseline treatment groups 344 242 98 98 100 0 50 100 150 200 250 300 350 400 p at ie n ts w h o c o m p le te d s u rv e y, n treatment group group 1: apremilast group 2: tnfi group 3: ustekinumab group 4: topical/phototherapy group 5: exploratorya athe exploratory group included patients who were using nonprescription treatments (n = 36), patients who had never received treatment (n = 17), and patients who had received treatment in the past but were not currently receiving treatment (n = 47). tnfi, tumor necrosis factor inhibitor. figure 2. key baseline characteristics, by sex (a) and race/ethnicitya (b) 74.9% 14.1% 2% 2% 0.2% 2.4% 6.1% white black american indian/ alaska native asian native hawaiian/ other pacific islander other preferred not to answer b.a. male female preferred not to answer 32.0% 67.7% 0.3% apercentages sum to >100% because respondents could select multiple races/ethnicities, as applicable. figure 3. key baseline characteristics for all respondents by insurance typea 13.6% 11.9% 54.5% 21.1% 2.2% 3.4% medicare medicaid employer-sponsored private insurance individually purchased private insurance uninsured military/veterans' coverage apercentages sum to >100% because respondents could select more than 1 insurance type, as applicable. table 1. key baseline characteristics for all respondents by patient age category all respondents (n = 882) mean 45.71 median (q1–q3) 45 range 18–76 q1–q3, quartiles 1–3. table 2. key baseline clinical characteristics parameter statistic or category all respondents, n = 882 (%) treatment status, n (%) currently receiving treatment 818 (92.8) was receiving treatment but has stopped 47 (5.3) never received treatment 17 (1.9) treatment duration, years mean (sd) 2.86 (4.81) median (q1–q3) 1.0 (0.0–3.0) range 0.0–42.0 current treatment type, n (%) over-the-counter nonprescription 225 (27.5) topical prescription steroid 230 (28.1) topical vitamin d analog 49 (6.0) other topical treatment 55 (6.7) ultraviolet light/phototherapy 51 (6.2) apremilast 356 (43.5) ustekinumab 101 (12.3) tnfi treatment 251 (30.7) psoriasis severity over the past week, n (%) none 31 (14.8) very mild 155 (17.6) mild 162 (18.4) moderate 322 (36.5) severe 86 (9.8) very severe 26 (2.9) bsa, body surface area; q1–q3, quartiles 1–3; sd, standard deviation; tnfi, tumor necrosis factor inhibitor. • among patients who were currently receiving treatment or who had never received treatment (n = 835), apremilast (41.2%) and tnfis (29.0%) were the most commonly used treatments, and otc or no treatment was the least common group (6.3%) (table 3) • of patients who had never received treatment, 88.2% expressed intent to start the new oral psoriasis treatment, compared with 80.6% of patients who used nonprescription otc treatment, 75.5% of patients who used ustekinumab, 74.0% of patients who used a tnfi, 69.4% of patients who used topical therapy, and 55.2% of patients who used apremilast (figure 4) • willingness to start the new, once-daily oral treatment was high across all groups, including patients currently using apremilast • in response to questions about the new treatment, 83.7% reported that it would be convenient, 65.0% reported that it would cause less anxiety than an injection or infusion, 55.3% reported that it would interfere less with their everyday life, and 50.2% reported that it would reduce their symptoms more than their current psoriasis treatment (figure 5) table 3. intent to start a new once-daily oral psoriasis treatment variable category intent to start new treatment all, n = 835 (%) yes, n = 555 (%) no, n = 280 (%) treatment group apremilast 344 (41.2) 190 (34.2) 154 (55.0) tnfi 242 (29.0) 179 (32.3) 63 (22.5) ustekinumab 98 (11.7) 74 (13.3) 24 (8.6) topical therapy 98 (11.7) 68 (12.3) 30 (10.7) otc or no treatment 53 (6.3) 44 (7.9) 9 (3.2) race/ethnicity white 610 (73.1) 390 (70.3) 220 (78.6) black 114 (13.7) 95 (17.1) 19 (6.8) asian, american indian/alaska native, native hawaiian/other pacifi c islander 32 (3.8) 21 (3.8) 11 (3.9) preferred not to answer 54 (6.5) 29 (5.2) 25 (8.9) other 25 (3.0) 20 (3.6) 5 (1.8) psoriasis severity over the past week (based on a 6-point scale) none 130 (15.6) 48 (8.6) 82 (29.3) mild 308 (36.9) 197 (35.5) 111 (39.6) moderate 298 (35.7) 228 (41.1) 70 (25.0) severe 99 (11.9) 82 (14.8) 17 (6.1) otc, over the counter; tnfi, tumor necrosis factor inhibitor. figure 4. intent to start a new once-daily oral treatment, by treatment group (a), race/ ethnicity (b), and psoriasis severity over the past week (c), all p < 0.001 55.2% 74.0% 75.5% 69.4% 83.0% 0 10 20 30 40 50 60 70 80 90 100 ap re m ila st tn fi us te ki nu m ab to pi ca l t he ra py w hi te bl ac k pr ef er re d no t to a ns we r ot he r no ne mi ld mo de ra te se ve re ot c or n o tr ea tm en t as ia n, a m er ic an in di an / al as ka n at iv e, n at iv e ha wa iia n/ ot he r p ac ifi c isl an de r p at ie n ts , % 63.9% 83.3% 65.6% 53.7% 80.0% a. b. 36.9% 64.0% 76.5% 82.8% c. 0 10 20 30 40 50 60 70 80 90 100 p at ie n ts , % 0 10 20 30 40 50 60 70 80 90 100 p at ie n ts , % otc, over the counter; tnfi, tumor necrosis factor inhibitor. figure 5. views on a new once-daily oral treatment, by treatment group 0 10 20 30 40 50 60 70 80 90 100 p at ie n ts , % yes neither yes nor no no yes neither yes nor no no yes neither yes nor no no yes neither yes nor no no yes no less interference with daily life (p < 0.001) convenience of treatment (p = 0.094) less anxiety than with injection/infusion (p = 0.041) reduction in symptoms compared with current treatment (p < 0.001) intent to start new oral psoriasis treatment (p < 0.001) apremilast (n = 344) tnfi (n = 242) ustekinumab (n = 98) topical therapy/phototherapy (n = 98) tnfi, tumor necrosis factor inhibitor. • only treatment group, race/ethnicity, and psoriasis severity were statistically significant factors in the model • the following responses were examined for intent to start a new once-daily oral treatment (yes/no), by selected categories: — 83% of black respondents would start the new once-daily oral treatment • compared with white patients, the odds ratio (or) of intent to start the new treatment was 2.4 (95% confidence interval [ci], 1.4–4.2) among black respondents (p = 0.036) — intent to start the new once-daily oral treatment increased with psoriasis severity over the past week, with 76.5% of respondents with moderate psoriasis and 82.8% of respondents with severe disease answering “yes” • compared with patients with no psoriasis symptoms or signs over the past week, the or of intent to start the new treatment was 3.2 (95% ci, 2.0–4.9) among patients with mild psoriasis, 5.0 (95% ci, 3.1–8.2) among patients with moderate psoriasis, and 7.6 (95% ci, 3.9–15.0) among patients with severe psoriasis; all p < 0.001 — 79.6% of patients who responded that the new once-daily oral treatment would cause them less anxiety than an injection would start the new treatment — 87.6% of respondents who believed that the new once-daily oral treatment would reduce their symptoms more than their current treatment would start the new treatment • asked to rank characteristics of psoriasis treatment in order of importance, 58.3% of respondents ranked “extent of skin clearance” as first or second, while 43.7% ranked “route of administration” as first or second (figure 6) • laboratory monitoring was ranked least important by more than half (53.0%) of the patients figure 6. reason for treatment choice ranking 37.1 22.8 17.0 11.9 10.0 1.3 21.2 20.9 15.0 20.3 19.1 3.5 22.1 18.6 15.5 20.2 18.0 5.6 12.2 19.1 22.3 19.8 14.7 11.8 5.9 12.4 21.3 19.5 16.0 24.9 1.5 6.2 8.8 8.3 22.2 53.0 0 10 20 30 40 50 60 sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g rank 1 (p < 0.001) rank 2 (p = 0.005) rank 3 (p = 0.030) rank 4 (p = 0.233) rank 5 (p = 0.005) rank 6 (p < 0.001) p at ie n ts , % conclusions • this large, real-world study provided an account of how psoriasis impacts patients’ lives and treatment choices • patients with severe disease, black patients, and patients receiving injectable treatments were more likely to choose the new oral treatment compared with patients with mild disease, white patients, and patients receiving apremilast, respectively • willingness to start the new psoriasis treatment was common among all treatment groups • the new treatment was viewed as causing less anxiety compared with injectables across all treatment groups • extent of skin clearance and route of administration were reported as the top-ranked reasons for patients' psoriasis treatment choice • consideration of the treatment characteristics that drive the decision-making of patients with psoriasis is crucial for making effective treatment recommendations in clinical practice reference 1. feldman sr, et al. j health econ outcomes res. 2016;4:141-157. acknowledgments • this study was sponsored by bristol myers squibb • medical writing and editorial assistance was provided by tulika bhushan bahukhandi, rph, ms, of peloton advantage, llc, an open health company, and funded by bristol myers squibb disclosures • awa: has served as a research investigator, scientific advisor, and/or speaker for abbvie, almirall, arcutis biotherapeutics, aslan, beiersdorf, boehringer ingelheim/parexel, bristol myers squibb, dermavant, dermira, eli lilly, epi, incyte, leo, janssen, nimbus, novartis, ortho dermatologics, pfizer, sanofi genzyme, sun, regeneron, and ucb • ls, dd, sk, and vp: employees of and may own stock options in bristol myers squibb • nj, sr, sj, and dp: employees of open health, which received consulting fees from bristol myers squibb • dw and kb: employees of rti health solutions, which received consulting fees from bristol myers squibb scientific content on demand to request a copy of this poster: scan qr code via a barcode reader application qr codes are valid for 30 days after the congress presentation date. evaluating treatment choice among patients with moderate or severe psoriasis in the united states april w. armstrong,1 sayeli jayade,2 sanika rege,2 namita joshi,2 vardhaman patel,3 david davidson,3 samaneh kalirai,3 daniel wolin,4 kimberly boyle,4 dipen patel,2 lauren seigel3 1keck school of medicine, university of southern california, los angeles, ca; 2open health, bethesda, md; 3bristol myers squibb, princeton, nj; 4rti health solutions, research triangle park, nc presented at the 2022 fall clinical dermatology conference; october 20–23, 2022; las vegas, nv this poster may not be reproduced without written permission from the authors.email for april w. armstrong, md, mph: aprilarmstrong@post.harvard.edu synopsis • while several psoriasis treatments are available and in development, different treatment modalities are associated with varying effectiveness, risks, and economic burden, and these factors are likely to influence patients’ decisions related to their psoriasis treatment1 • this study explored the element of treatment decision-making driven by patient experiences — a cross-sectional, web-based survey captured the demographic and clinical characteristics, treatment attributes affecting therapeutic decisions, and perceptions of a new, hypothetical, once-daily oral psoriasis treatment (deucravacitinib) among patients with moderate to severe plaque psoriasis • understanding the factors that drive patients’ treatment preference is crucial for guiding clinical decision-making objectives primary • to identify factors associated with the choice of a new once-daily oral psoriasis treatment with efficacy superior to that of existing oral therapies in patients with moderate to severe psoriasis currently receiving apremilast, tumor necrosis factor inhibitors (tnfis), ustekinumab, topicals, or nonprescription treatments secondary • to rank the importance of treatment attributes to patients with moderate to severe psoriasis using apremilast, tnfis, ustekinumab, topicals, or nonprescription treatments • to elicit views on a new once-daily oral psoriasis treatment among patients with moderate to severe psoriasis using apremilast, tnfis, ustekinumab, topicals, or nonprescription treatments target product profile (deucravacitinib) • tablet formulation with once-daily dosing • clinical studies showed: — 53% of patients reported clear/mostly clear skin within 4 months — 83% of patients who reported a 75% reduction in psoriasis severity maintained this improvement at 1 year — non-serious adverse events, such as cold-like symptoms, headache, diarrhea, nausea, rash, and risk of herpes infection, led to few discontinuations • regular laboratory monitoring is not required, although pre-initiation testing may be needed • out-of-pocket costs may be similar to those of the alternative psoriasis treatments in consideration methods • a cross-sectional, web-based survey of the demographics and clinical characteristics of patients with psoriasis, their views on treatment characteristics that affect treatment-related decisions, and their perceptions of a new, hypothetical, once-daily oral psoriasis treatment • patients were assigned to predefined treatment groups: apremilast, a tnfi, ustekinumab, a topical therapy/phototherapy, and over-the-counter (otc) treatments or no treatment, based on their self-reported current treatment at the time of the survey • a hypothetical psoriasis treatment profile, described by dosage, efficacy, adverse effects, and out-of-pocket costs, was shown to the patients to elicit their views on: (1) interference with everyday life, (2) convenience, (3) treatment-related anxiety, and likelihood of initiating treatment, both (4) without a safety warning and (5) with a safety warning inclusion criteria • ≥18 years of age • residing in the united states • able to read and understand english • physician-diagnosed (self-reported) moderate or severe plaque psoriasis exclusion criteria • mild psoriasis • lack of online consent for the web-based survey data collection process • the study was reviewed and approved by an institutional review board • the study used a convenience sample of patients with moderate or severe psoriasis who were recruited by global perspectives to collect patient-reported data • patients were asked to complete an electronic patient survey that included questions from patient-reported outcome (pro) instruments and de novo questions • potential survey participants were provided with a link to the survey and completed screening questions to determine eligibility, followed by an informed consent checkbox • the final survey was administered to 882 patients statistical analysis • stepwise multivariable logistic regression was conducted to determine sociodemographic and clinical characteristics associated with the choice of the new treatment among patients who were currently receiving treatment or who had never received treatment — independent variables: treatment group, age, sex, race/ethnicity, psoriasis severity over the past week, comorbidities, disease and treatment duration, presence of psoriatic arthritis (psa) at baseline, number of flares, and number of body regions affected • treatment attributes (route of administration, extent of skin clearance, laboratory monitoring, durability, safety, and dosing frequency) were ranked as an ordinal category (scale of 1–6) by patients • chi-square test was conducted to detect significant differences between patient rankings of each treatment attribute and to assess the variations in patient views on the new oral treatment results • figure 1 shows the responses of the 5 baseline treatment groups surveyed • the study sample included 882 patients (mean age = 45.7 [±12.8] years); the majority were female (67.7%), most were white (74.9%), and their average duration of time since psoriasis diagnosis was 14.9 (±11.8) years (figures 2 and 3; table 1) • of 882 patients, 818 (92.8%) were currently receiving treatment and had been on their current treatment for a mean of 2.9 (±4.8) years (table 2) • with their current treatment regimen, 50.8% of patients in the total study population described their psoriasis over the past week as mild, very mild, or none, while 36.5% reported it as moderate and 12.7% reported it as severe or very severe (table 2) figure 1. targeted baseline treatment groups 344 242 98 98 100 0 50 100 150 200 250 300 350 400 p at ie n ts w h o c o m p le te d s u rv e y, n treatment group group 1: apremilast group 2: tnfi group 3: ustekinumab group 4: topical/phototherapy group 5: exploratorya athe exploratory group included patients who were using nonprescription treatments (n = 36), patients who had never received treatment (n = 17), and patients who had received treatment in the past but were not currently receiving treatment (n = 47). tnfi, tumor necrosis factor inhibitor. figure 2. key baseline characteristics, by sex (a) and race/ethnicitya (b) 74.9% 14.1% 2% 2% 0.2% 2.4% 6.1% white black american indian/ alaska native asian native hawaiian/ other pacific islander other preferred not to answer b.a. male female preferred not to answer 32.0% 67.7% 0.3% apercentages sum to >100% because respondents could select multiple races/ethnicities, as applicable. figure 3. key baseline characteristics for all respondents by insurance typea 13.6% 11.9% 54.5% 21.1% 2.2% 3.4% medicare medicaid employer-sponsored private insurance individually purchased private insurance uninsured military/veterans' coverage apercentages sum to >100% because respondents could select more than 1 insurance type, as applicable. table 1. key baseline characteristics for all respondents by patient age category all respondents (n = 882) mean 45.71 median (q1–q3) 45 range 18–76 q1–q3, quartiles 1–3. table 2. key baseline clinical characteristics parameter statistic or category all respondents, n = 882 (%) treatment status, n (%) currently receiving treatment 818 (92.8) was receiving treatment but has stopped 47 (5.3) never received treatment 17 (1.9) treatment duration, years mean (sd) 2.86 (4.81) median (q1–q3) 1.0 (0.0–3.0) range 0.0–42.0 current treatment type, n (%) over-the-counter nonprescription 225 (27.5) topical prescription steroid 230 (28.1) topical vitamin d analog 49 (6.0) other topical treatment 55 (6.7) ultraviolet light/phototherapy 51 (6.2) apremilast 356 (43.5) ustekinumab 101 (12.3) tnfi treatment 251 (30.7) psoriasis severity over the past week, n (%) none 31 (14.8) very mild 155 (17.6) mild 162 (18.4) moderate 322 (36.5) severe 86 (9.8) very severe 26 (2.9) bsa, body surface area; q1–q3, quartiles 1–3; sd, standard deviation; tnfi, tumor necrosis factor inhibitor. • among patients who were currently receiving treatment or who had never received treatment (n = 835), apremilast (41.2%) and tnfis (29.0%) were the most commonly used treatments, and otc or no treatment was the least common group (6.3%) (table 3) • of patients who had never received treatment, 88.2% expressed intent to start the new oral psoriasis treatment, compared with 80.6% of patients who used nonprescription otc treatment, 75.5% of patients who used ustekinumab, 74.0% of patients who used a tnfi, 69.4% of patients who used topical therapy, and 55.2% of patients who used apremilast (figure 4) • willingness to start the new, once-daily oral treatment was high across all groups, including patients currently using apremilast • in response to questions about the new treatment, 83.7% reported that it would be convenient, 65.0% reported that it would cause less anxiety than an injection or infusion, 55.3% reported that it would interfere less with their everyday life, and 50.2% reported that it would reduce their symptoms more than their current psoriasis treatment (figure 5) table 3. intent to start a new once-daily oral psoriasis treatment variable category intent to start new treatment all, n = 835 (%) yes, n = 555 (%) no, n = 280 (%) treatment group apremilast 344 (41.2) 190 (34.2) 154 (55.0) tnfi 242 (29.0) 179 (32.3) 63 (22.5) ustekinumab 98 (11.7) 74 (13.3) 24 (8.6) topical therapy 98 (11.7) 68 (12.3) 30 (10.7) otc or no treatment 53 (6.3) 44 (7.9) 9 (3.2) race/ethnicity white 610 (73.1) 390 (70.3) 220 (78.6) black 114 (13.7) 95 (17.1) 19 (6.8) asian, american indian/alaska native, native hawaiian/other pacifi c islander 32 (3.8) 21 (3.8) 11 (3.9) preferred not to answer 54 (6.5) 29 (5.2) 25 (8.9) other 25 (3.0) 20 (3.6) 5 (1.8) psoriasis severity over the past week (based on a 6-point scale) none 130 (15.6) 48 (8.6) 82 (29.3) mild 308 (36.9) 197 (35.5) 111 (39.6) moderate 298 (35.7) 228 (41.1) 70 (25.0) severe 99 (11.9) 82 (14.8) 17 (6.1) otc, over the counter; tnfi, tumor necrosis factor inhibitor. figure 4. intent to start a new once-daily oral treatment, by treatment group (a), race/ ethnicity (b), and psoriasis severity over the past week (c), all p < 0.001 55.2% 74.0% 75.5% 69.4% 83.0% 0 10 20 30 40 50 60 70 80 90 100 ap re m ila st tn fi us te ki nu m ab to pi ca l t he ra py w hi te bl ac k pr ef er re d no t to a ns we r ot he r no ne mi ld mo de ra te se ve re ot c or n o tr ea tm en t as ia n, a m er ic an in di an / al as ka n at iv e, n at iv e ha wa iia n/ ot he r p ac ifi c isl an de r p at ie n ts , % 63.9% 83.3% 65.6% 53.7% 80.0% a. b. 36.9% 64.0% 76.5% 82.8% c. 0 10 20 30 40 50 60 70 80 90 100 p at ie n ts , % 0 10 20 30 40 50 60 70 80 90 100 p at ie n ts , % otc, over the counter; tnfi, tumor necrosis factor inhibitor. figure 5. views on a new once-daily oral treatment, by treatment group 0 10 20 30 40 50 60 70 80 90 100 p at ie n ts , % yes neither yes nor no no yes neither yes nor no no yes neither yes nor no no yes neither yes nor no no yes no less interference with daily life (p < 0.001) convenience of treatment (p = 0.094) less anxiety than with injection/infusion (p = 0.041) reduction in symptoms compared with current treatment (p < 0.001) intent to start new oral psoriasis treatment (p < 0.001) apremilast (n = 344) tnfi (n = 242) ustekinumab (n = 98) topical therapy/phototherapy (n = 98) tnfi, tumor necrosis factor inhibitor. • only treatment group, race/ethnicity, and psoriasis severity were statistically significant factors in the model • the following responses were examined for intent to start a new once-daily oral treatment (yes/no), by selected categories: — 83% of black respondents would start the new once-daily oral treatment • compared with white patients, the odds ratio (or) of intent to start the new treatment was 2.4 (95% confidence interval [ci], 1.4–4.2) among black respondents (p = 0.036) — intent to start the new once-daily oral treatment increased with psoriasis severity over the past week, with 76.5% of respondents with moderate psoriasis and 82.8% of respondents with severe disease answering “yes” • compared with patients with no psoriasis symptoms or signs over the past week, the or of intent to start the new treatment was 3.2 (95% ci, 2.0–4.9) among patients with mild psoriasis, 5.0 (95% ci, 3.1–8.2) among patients with moderate psoriasis, and 7.6 (95% ci, 3.9–15.0) among patients with severe psoriasis; all p < 0.001 — 79.6% of patients who responded that the new once-daily oral treatment would cause them less anxiety than an injection would start the new treatment — 87.6% of respondents who believed that the new once-daily oral treatment would reduce their symptoms more than their current treatment would start the new treatment • asked to rank characteristics of psoriasis treatment in order of importance, 58.3% of respondents ranked “extent of skin clearance” as first or second, while 43.7% ranked “route of administration” as first or second (figure 6) • laboratory monitoring was ranked least important by more than half (53.0%) of the patients figure 6. reason for treatment choice ranking 37.1 22.8 17.0 11.9 10.0 1.3 21.2 20.9 15.0 20.3 19.1 3.5 22.1 18.6 15.5 20.2 18.0 5.6 12.2 19.1 22.3 19.8 14.7 11.8 5.9 12.4 21.3 19.5 16.0 24.9 1.5 6.2 8.8 8.3 22.2 53.0 0 10 20 30 40 50 60 sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g rank 1 (p < 0.001) rank 2 (p = 0.005) rank 3 (p = 0.030) rank 4 (p = 0.233) rank 5 (p = 0.005) rank 6 (p < 0.001) p at ie n ts , % conclusions • this large, real-world study provided an account of how psoriasis impacts patients’ lives and treatment choices • patients with severe disease, black patients, and patients receiving injectable treatments were more likely to choose the new oral treatment compared with patients with mild disease, white patients, and patients receiving apremilast, respectively • willingness to start the new psoriasis treatment was common among all treatment groups • the new treatment was viewed as causing less anxiety compared with injectables across all treatment groups • extent of skin clearance and route of administration were reported as the top-ranked reasons for patients' psoriasis treatment choice • consideration of the treatment characteristics that drive the decision-making of patients with psoriasis is crucial for making effective treatment recommendations in clinical practice reference 1. feldman sr, et al. j health econ outcomes res. 2016;4:141-157. acknowledgments • this study was sponsored by bristol myers squibb • medical writing and editorial assistance was provided by tulika bhushan bahukhandi, rph, ms, of peloton advantage, llc, an open health company, and funded by bristol myers squibb disclosures • awa: has served as a research investigator, scientific advisor, and/or speaker for abbvie, almirall, arcutis biotherapeutics, aslan, beiersdorf, boehringer ingelheim/parexel, bristol myers squibb, dermavant, dermira, eli lilly, epi, incyte, leo, janssen, nimbus, novartis, ortho dermatologics, pfizer, sanofi genzyme, sun, regeneron, and ucb • ls, dd, sk, and vp: employees of and may own stock options in bristol myers squibb • nj, sr, sj, and dp: employees of open health, which received consulting fees from bristol myers squibb • dw and kb: employees of rti health solutions, which received consulting fees from bristol myers squibb scientific content on demand to request a copy of this poster: scan qr code via a barcode reader application qr codes are valid for 30 days after the congress presentation date. evaluating treatment choice among patients with moderate or severe psoriasis in the united states april w. armstrong,1 sayeli jayade,2 sanika rege,2 namita joshi,2 vardhaman patel,3 david davidson,3 samaneh kalirai,3 daniel wolin,4 kimberly boyle,4 dipen patel,2 lauren seigel3 1keck school of medicine, university of southern california, los angeles, ca; 2open health, bethesda, md; 3bristol myers squibb, princeton, nj; 4rti health solutions, research triangle park, nc presented at the 2022 fall clinical dermatology conference; october 20–23, 2022; las vegas, nv this poster may not be reproduced without written permission from the authors.email for april w. armstrong, md, mph: aprilarmstrong@post.harvard.edu synopsis • while several psoriasis treatments are available and in development, different treatment modalities are associated with varying effectiveness, risks, and economic burden, and these factors are likely to influence patients’ decisions related to their psoriasis treatment1 • this study explored the element of treatment decision-making driven by patient experiences — a cross-sectional, web-based survey captured the demographic and clinical characteristics, treatment attributes affecting therapeutic decisions, and perceptions of a new, hypothetical, once-daily oral psoriasis treatment (deucravacitinib) among patients with moderate to severe plaque psoriasis • understanding the factors that drive patients’ treatment preference is crucial for guiding clinical decision-making objectives primary • to identify factors associated with the choice of a new once-daily oral psoriasis treatment with efficacy superior to that of existing oral therapies in patients with moderate to severe psoriasis currently receiving apremilast, tumor necrosis factor inhibitors (tnfis), ustekinumab, topicals, or nonprescription treatments secondary • to rank the importance of treatment attributes to patients with moderate to severe psoriasis using apremilast, tnfis, ustekinumab, topicals, or nonprescription treatments • to elicit views on a new once-daily oral psoriasis treatment among patients with moderate to severe psoriasis using apremilast, tnfis, ustekinumab, topicals, or nonprescription treatments target product profile (deucravacitinib) • tablet formulation with once-daily dosing • clinical studies showed: — 53% of patients reported clear/mostly clear skin within 4 months — 83% of patients who reported a 75% reduction in psoriasis severity maintained this improvement at 1 year — non-serious adverse events, such as cold-like symptoms, headache, diarrhea, nausea, rash, and risk of herpes infection, led to few discontinuations • regular laboratory monitoring is not required, although pre-initiation testing may be needed • out-of-pocket costs may be similar to those of the alternative psoriasis treatments in consideration methods • a cross-sectional, web-based survey of the demographics and clinical characteristics of patients with psoriasis, their views on treatment characteristics that affect treatment-related decisions, and their perceptions of a new, hypothetical, once-daily oral psoriasis treatment • patients were assigned to predefined treatment groups: apremilast, a tnfi, ustekinumab, a topical therapy/phototherapy, and over-the-counter (otc) treatments or no treatment, based on their self-reported current treatment at the time of the survey • a hypothetical psoriasis treatment profile, described by dosage, efficacy, adverse effects, and out-of-pocket costs, was shown to the patients to elicit their views on: (1) interference with everyday life, (2) convenience, (3) treatment-related anxiety, and likelihood of initiating treatment, both (4) without a safety warning and (5) with a safety warning inclusion criteria • ≥18 years of age • residing in the united states • able to read and understand english • physician-diagnosed (self-reported) moderate or severe plaque psoriasis exclusion criteria • mild psoriasis • lack of online consent for the web-based survey data collection process • the study was reviewed and approved by an institutional review board • the study used a convenience sample of patients with moderate or severe psoriasis who were recruited by global perspectives to collect patient-reported data • patients were asked to complete an electronic patient survey that included questions from patient-reported outcome (pro) instruments and de novo questions • potential survey participants were provided with a link to the survey and completed screening questions to determine eligibility, followed by an informed consent checkbox • the final survey was administered to 882 patients statistical analysis • stepwise multivariable logistic regression was conducted to determine sociodemographic and clinical characteristics associated with the choice of the new treatment among patients who were currently receiving treatment or who had never received treatment — independent variables: treatment group, age, sex, race/ethnicity, psoriasis severity over the past week, comorbidities, disease and treatment duration, presence of psoriatic arthritis (psa) at baseline, number of flares, and number of body regions affected • treatment attributes (route of administration, extent of skin clearance, laboratory monitoring, durability, safety, and dosing frequency) were ranked as an ordinal category (scale of 1–6) by patients • chi-square test was conducted to detect significant differences between patient rankings of each treatment attribute and to assess the variations in patient views on the new oral treatment results • figure 1 shows the responses of the 5 baseline treatment groups surveyed • the study sample included 882 patients (mean age = 45.7 [±12.8] years); the majority were female (67.7%), most were white (74.9%), and their average duration of time since psoriasis diagnosis was 14.9 (±11.8) years (figures 2 and 3; table 1) • of 882 patients, 818 (92.8%) were currently receiving treatment and had been on their current treatment for a mean of 2.9 (±4.8) years (table 2) • with their current treatment regimen, 50.8% of patients in the total study population described their psoriasis over the past week as mild, very mild, or none, while 36.5% reported it as moderate and 12.7% reported it as severe or very severe (table 2) figure 1. targeted baseline treatment groups 344 242 98 98 100 0 50 100 150 200 250 300 350 400 p at ie n ts w h o c o m p le te d s u rv e y, n treatment group group 1: apremilast group 2: tnfi group 3: ustekinumab group 4: topical/phototherapy group 5: exploratorya athe exploratory group included patients who were using nonprescription treatments (n = 36), patients who had never received treatment (n = 17), and patients who had received treatment in the past but were not currently receiving treatment (n = 47). tnfi, tumor necrosis factor inhibitor. figure 2. key baseline characteristics, by sex (a) and race/ethnicitya (b) 74.9% 14.1% 2% 2% 0.2% 2.4% 6.1% white black american indian/ alaska native asian native hawaiian/ other pacific islander other preferred not to answer b.a. male female preferred not to answer 32.0% 67.7% 0.3% apercentages sum to >100% because respondents could select multiple races/ethnicities, as applicable. figure 3. key baseline characteristics for all respondents by insurance typea 13.6% 11.9% 54.5% 21.1% 2.2% 3.4% medicare medicaid employer-sponsored private insurance individually purchased private insurance uninsured military/veterans' coverage apercentages sum to >100% because respondents could select more than 1 insurance type, as applicable. table 1. key baseline characteristics for all respondents by patient age category all respondents (n = 882) mean 45.71 median (q1–q3) 45 range 18–76 q1–q3, quartiles 1–3. table 2. key baseline clinical characteristics parameter statistic or category all respondents, n = 882 (%) treatment status, n (%) currently receiving treatment 818 (92.8) was receiving treatment but has stopped 47 (5.3) never received treatment 17 (1.9) treatment duration, years mean (sd) 2.86 (4.81) median (q1–q3) 1.0 (0.0–3.0) range 0.0–42.0 current treatment type, n (%) over-the-counter nonprescription 225 (27.5) topical prescription steroid 230 (28.1) topical vitamin d analog 49 (6.0) other topical treatment 55 (6.7) ultraviolet light/phototherapy 51 (6.2) apremilast 356 (43.5) ustekinumab 101 (12.3) tnfi treatment 251 (30.7) psoriasis severity over the past week, n (%) none 31 (14.8) very mild 155 (17.6) mild 162 (18.4) moderate 322 (36.5) severe 86 (9.8) very severe 26 (2.9) bsa, body surface area; q1–q3, quartiles 1–3; sd, standard deviation; tnfi, tumor necrosis factor inhibitor. • among patients who were currently receiving treatment or who had never received treatment (n = 835), apremilast (41.2%) and tnfis (29.0%) were the most commonly used treatments, and otc or no treatment was the least common group (6.3%) (table 3) • of patients who had never received treatment, 88.2% expressed intent to start the new oral psoriasis treatment, compared with 80.6% of patients who used nonprescription otc treatment, 75.5% of patients who used ustekinumab, 74.0% of patients who used a tnfi, 69.4% of patients who used topical therapy, and 55.2% of patients who used apremilast (figure 4) • willingness to start the new, once-daily oral treatment was high across all groups, including patients currently using apremilast • in response to questions about the new treatment, 83.7% reported that it would be convenient, 65.0% reported that it would cause less anxiety than an injection or infusion, 55.3% reported that it would interfere less with their everyday life, and 50.2% reported that it would reduce their symptoms more than their current psoriasis treatment (figure 5) table 3. intent to start a new once-daily oral psoriasis treatment variable category intent to start new treatment all, n = 835 (%) yes, n = 555 (%) no, n = 280 (%) treatment group apremilast 344 (41.2) 190 (34.2) 154 (55.0) tnfi 242 (29.0) 179 (32.3) 63 (22.5) ustekinumab 98 (11.7) 74 (13.3) 24 (8.6) topical therapy 98 (11.7) 68 (12.3) 30 (10.7) otc or no treatment 53 (6.3) 44 (7.9) 9 (3.2) race/ethnicity white 610 (73.1) 390 (70.3) 220 (78.6) black 114 (13.7) 95 (17.1) 19 (6.8) asian, american indian/alaska native, native hawaiian/other pacifi c islander 32 (3.8) 21 (3.8) 11 (3.9) preferred not to answer 54 (6.5) 29 (5.2) 25 (8.9) other 25 (3.0) 20 (3.6) 5 (1.8) psoriasis severity over the past week (based on a 6-point scale) none 130 (15.6) 48 (8.6) 82 (29.3) mild 308 (36.9) 197 (35.5) 111 (39.6) moderate 298 (35.7) 228 (41.1) 70 (25.0) severe 99 (11.9) 82 (14.8) 17 (6.1) otc, over the counter; tnfi, tumor necrosis factor inhibitor. figure 4. intent to start a new once-daily oral treatment, by treatment group (a), race/ ethnicity (b), and psoriasis severity over the past week (c), all p < 0.001 55.2% 74.0% 75.5% 69.4% 83.0% 0 10 20 30 40 50 60 70 80 90 100 ap re m ila st tn fi us te ki nu m ab to pi ca l t he ra py w hi te bl ac k pr ef er re d no t to a ns we r ot he r no ne mi ld mo de ra te se ve re ot c or n o tr ea tm en t as ia n, a m er ic an in di an / al as ka n at iv e, n at iv e ha wa iia n/ ot he r p ac ifi c isl an de r p at ie n ts , % 63.9% 83.3% 65.6% 53.7% 80.0% a. b. 36.9% 64.0% 76.5% 82.8% c. 0 10 20 30 40 50 60 70 80 90 100 p at ie n ts , % 0 10 20 30 40 50 60 70 80 90 100 p at ie n ts , % otc, over the counter; tnfi, tumor necrosis factor inhibitor. figure 5. views on a new once-daily oral treatment, by treatment group 0 10 20 30 40 50 60 70 80 90 100 p at ie n ts , % yes neither yes nor no no yes neither yes nor no no yes neither yes nor no no yes neither yes nor no no yes no less interference with daily life (p < 0.001) convenience of treatment (p = 0.094) less anxiety than with injection/infusion (p = 0.041) reduction in symptoms compared with current treatment (p < 0.001) intent to start new oral psoriasis treatment (p < 0.001) apremilast (n = 344) tnfi (n = 242) ustekinumab (n = 98) topical therapy/phototherapy (n = 98) tnfi, tumor necrosis factor inhibitor. • only treatment group, race/ethnicity, and psoriasis severity were statistically significant factors in the model • the following responses were examined for intent to start a new once-daily oral treatment (yes/no), by selected categories: — 83% of black respondents would start the new once-daily oral treatment • compared with white patients, the odds ratio (or) of intent to start the new treatment was 2.4 (95% confidence interval [ci], 1.4–4.2) among black respondents (p = 0.036) — intent to start the new once-daily oral treatment increased with psoriasis severity over the past week, with 76.5% of respondents with moderate psoriasis and 82.8% of respondents with severe disease answering “yes” • compared with patients with no psoriasis symptoms or signs over the past week, the or of intent to start the new treatment was 3.2 (95% ci, 2.0–4.9) among patients with mild psoriasis, 5.0 (95% ci, 3.1–8.2) among patients with moderate psoriasis, and 7.6 (95% ci, 3.9–15.0) among patients with severe psoriasis; all p < 0.001 — 79.6% of patients who responded that the new once-daily oral treatment would cause them less anxiety than an injection would start the new treatment — 87.6% of respondents who believed that the new once-daily oral treatment would reduce their symptoms more than their current treatment would start the new treatment • asked to rank characteristics of psoriasis treatment in order of importance, 58.3% of respondents ranked “extent of skin clearance” as first or second, while 43.7% ranked “route of administration” as first or second (figure 6) • laboratory monitoring was ranked least important by more than half (53.0%) of the patients figure 6. reason for treatment choice ranking 37.1 22.8 17.0 11.9 10.0 1.3 21.2 20.9 15.0 20.3 19.1 3.5 22.1 18.6 15.5 20.2 18.0 5.6 12.2 19.1 22.3 19.8 14.7 11.8 5.9 12.4 21.3 19.5 16.0 24.9 1.5 6.2 8.8 8.3 22.2 53.0 0 10 20 30 40 50 60 sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g rank 1 (p < 0.001) rank 2 (p = 0.005) rank 3 (p = 0.030) rank 4 (p = 0.233) rank 5 (p = 0.005) rank 6 (p < 0.001) p at ie n ts , % conclusions • this large, real-world study provided an account of how psoriasis impacts patients’ lives and treatment choices • patients with severe disease, black patients, and patients receiving injectable treatments were more likely to choose the new oral treatment compared with patients with mild disease, white patients, and patients receiving apremilast, respectively • willingness to start the new psoriasis treatment was common among all treatment groups • the new treatment was viewed as causing less anxiety compared with injectables across all treatment groups • extent of skin clearance and route of administration were reported as the top-ranked reasons for patients' psoriasis treatment choice • consideration of the treatment characteristics that drive the decision-making of patients with psoriasis is crucial for making effective treatment recommendations in clinical practice reference 1. feldman sr, et al. j health econ outcomes res. 2016;4:141-157. acknowledgments • this study was sponsored by bristol myers squibb • medical writing and editorial assistance was provided by tulika bhushan bahukhandi, rph, ms, of peloton advantage, llc, an open health company, and funded by bristol myers squibb disclosures • awa: has served as a research investigator, scientific advisor, and/or speaker for abbvie, almirall, arcutis biotherapeutics, aslan, beiersdorf, boehringer ingelheim/parexel, bristol myers squibb, dermavant, dermira, eli lilly, epi, incyte, leo, janssen, nimbus, novartis, ortho dermatologics, pfizer, sanofi genzyme, sun, regeneron, and ucb • ls, dd, sk, and vp: employees of and may own stock options in bristol myers squibb • nj, sr, sj, and dp: employees of open health, which received consulting fees from bristol myers squibb • dw and kb: employees of rti health solutions, which received consulting fees from bristol myers squibb scientific content on demand to request a copy of this poster: scan qr code via a barcode reader application qr codes are valid for 30 days after the congress presentation date. evaluating treatment choice among patients with moderate or severe psoriasis in the united states april w. armstrong,1 sayeli jayade,2 sanika rege,2 namita joshi,2 vardhaman patel,3 david davidson,3 samaneh kalirai,3 daniel wolin,4 kimberly boyle,4 dipen patel,2 lauren seigel3 1keck school of medicine, university of southern california, los angeles, ca; 2open health, bethesda, md; 3bristol myers squibb, princeton, nj; 4rti health solutions, research triangle park, nc presented at the 2022 fall clinical dermatology conference; october 20–23, 2022; las vegas, nv this poster may not be reproduced without written permission from the authors.email for april w. armstrong, md, mph: aprilarmstrong@post.harvard.edu synopsis • while several psoriasis treatments are available and in development, different treatment modalities are associated with varying effectiveness, risks, and economic burden, and these factors are likely to influence patients’ decisions related to their psoriasis treatment1 • this study explored the element of treatment decision-making driven by patient experiences — a cross-sectional, web-based survey captured the demographic and clinical characteristics, treatment attributes affecting therapeutic decisions, and perceptions of a new, hypothetical, once-daily oral psoriasis treatment (deucravacitinib) among patients with moderate to severe plaque psoriasis • understanding the factors that drive patients’ treatment preference is crucial for guiding clinical decision-making objectives primary • to identify factors associated with the choice of a new once-daily oral psoriasis treatment with efficacy superior to that of existing oral therapies in patients with moderate to severe psoriasis currently receiving apremilast, tumor necrosis factor inhibitors (tnfis), ustekinumab, topicals, or nonprescription treatments secondary • to rank the importance of treatment attributes to patients with moderate to severe psoriasis using apremilast, tnfis, ustekinumab, topicals, or nonprescription treatments • to elicit views on a new once-daily oral psoriasis treatment among patients with moderate to severe psoriasis using apremilast, tnfis, ustekinumab, topicals, or nonprescription treatments target product profile (deucravacitinib) • tablet formulation with once-daily dosing • clinical studies showed: — 53% of patients reported clear/mostly clear skin within 4 months — 83% of patients who reported a 75% reduction in psoriasis severity maintained this improvement at 1 year — non-serious adverse events, such as cold-like symptoms, headache, diarrhea, nausea, rash, and risk of herpes infection, led to few discontinuations • regular laboratory monitoring is not required, although pre-initiation testing may be needed • out-of-pocket costs may be similar to those of the alternative psoriasis treatments in consideration methods • a cross-sectional, web-based survey of the demographics and clinical characteristics of patients with psoriasis, their views on treatment characteristics that affect treatment-related decisions, and their perceptions of a new, hypothetical, once-daily oral psoriasis treatment • patients were assigned to predefined treatment groups: apremilast, a tnfi, ustekinumab, a topical therapy/phototherapy, and over-the-counter (otc) treatments or no treatment, based on their self-reported current treatment at the time of the survey • a hypothetical psoriasis treatment profile, described by dosage, efficacy, adverse effects, and out-of-pocket costs, was shown to the patients to elicit their views on: (1) interference with everyday life, (2) convenience, (3) treatment-related anxiety, and likelihood of initiating treatment, both (4) without a safety warning and (5) with a safety warning inclusion criteria • ≥18 years of age • residing in the united states • able to read and understand english • physician-diagnosed (self-reported) moderate or severe plaque psoriasis exclusion criteria • mild psoriasis • lack of online consent for the web-based survey data collection process • the study was reviewed and approved by an institutional review board • the study used a convenience sample of patients with moderate or severe psoriasis who were recruited by global perspectives to collect patient-reported data • patients were asked to complete an electronic patient survey that included questions from patient-reported outcome (pro) instruments and de novo questions • potential survey participants were provided with a link to the survey and completed screening questions to determine eligibility, followed by an informed consent checkbox • the final survey was administered to 882 patients statistical analysis • stepwise multivariable logistic regression was conducted to determine sociodemographic and clinical characteristics associated with the choice of the new treatment among patients who were currently receiving treatment or who had never received treatment — independent variables: treatment group, age, sex, race/ethnicity, psoriasis severity over the past week, comorbidities, disease and treatment duration, presence of psoriatic arthritis (psa) at baseline, number of flares, and number of body regions affected • treatment attributes (route of administration, extent of skin clearance, laboratory monitoring, durability, safety, and dosing frequency) were ranked as an ordinal category (scale of 1–6) by patients • chi-square test was conducted to detect significant differences between patient rankings of each treatment attribute and to assess the variations in patient views on the new oral treatment results • figure 1 shows the responses of the 5 baseline treatment groups surveyed • the study sample included 882 patients (mean age = 45.7 [±12.8] years); the majority were female (67.7%), most were white (74.9%), and their average duration of time since psoriasis diagnosis was 14.9 (±11.8) years (figures 2 and 3; table 1) • of 882 patients, 818 (92.8%) were currently receiving treatment and had been on their current treatment for a mean of 2.9 (±4.8) years (table 2) • with their current treatment regimen, 50.8% of patients in the total study population described their psoriasis over the past week as mild, very mild, or none, while 36.5% reported it as moderate and 12.7% reported it as severe or very severe (table 2) figure 1. targeted baseline treatment groups 344 242 98 98 100 0 50 100 150 200 250 300 350 400 p at ie n ts w h o c o m p le te d s u rv e y, n treatment group group 1: apremilast group 2: tnfi group 3: ustekinumab group 4: topical/phototherapy group 5: exploratorya athe exploratory group included patients who were using nonprescription treatments (n = 36), patients who had never received treatment (n = 17), and patients who had received treatment in the past but were not currently receiving treatment (n = 47). tnfi, tumor necrosis factor inhibitor. figure 2. key baseline characteristics, by sex (a) and race/ethnicitya (b) 74.9% 14.1% 2% 2% 0.2% 2.4% 6.1% white black american indian/ alaska native asian native hawaiian/ other pacific islander other preferred not to answer b.a. male female preferred not to answer 32.0% 67.7% 0.3% apercentages sum to >100% because respondents could select multiple races/ethnicities, as applicable. figure 3. key baseline characteristics for all respondents by insurance typea 13.6% 11.9% 54.5% 21.1% 2.2% 3.4% medicare medicaid employer-sponsored private insurance individually purchased private insurance uninsured military/veterans' coverage apercentages sum to >100% because respondents could select more than 1 insurance type, as applicable. table 1. key baseline characteristics for all respondents by patient age category all respondents (n = 882) mean 45.71 median (q1–q3) 45 range 18–76 q1–q3, quartiles 1–3. table 2. key baseline clinical characteristics parameter statistic or category all respondents, n = 882 (%) treatment status, n (%) currently receiving treatment 818 (92.8) was receiving treatment but has stopped 47 (5.3) never received treatment 17 (1.9) treatment duration, years mean (sd) 2.86 (4.81) median (q1–q3) 1.0 (0.0–3.0) range 0.0–42.0 current treatment type, n (%) over-the-counter nonprescription 225 (27.5) topical prescription steroid 230 (28.1) topical vitamin d analog 49 (6.0) other topical treatment 55 (6.7) ultraviolet light/phototherapy 51 (6.2) apremilast 356 (43.5) ustekinumab 101 (12.3) tnfi treatment 251 (30.7) psoriasis severity over the past week, n (%) none 31 (14.8) very mild 155 (17.6) mild 162 (18.4) moderate 322 (36.5) severe 86 (9.8) very severe 26 (2.9) bsa, body surface area; q1–q3, quartiles 1–3; sd, standard deviation; tnfi, tumor necrosis factor inhibitor. • among patients who were currently receiving treatment or who had never received treatment (n = 835), apremilast (41.2%) and tnfis (29.0%) were the most commonly used treatments, and otc or no treatment was the least common group (6.3%) (table 3) • of patients who had never received treatment, 88.2% expressed intent to start the new oral psoriasis treatment, compared with 80.6% of patients who used nonprescription otc treatment, 75.5% of patients who used ustekinumab, 74.0% of patients who used a tnfi, 69.4% of patients who used topical therapy, and 55.2% of patients who used apremilast (figure 4) • willingness to start the new, once-daily oral treatment was high across all groups, including patients currently using apremilast • in response to questions about the new treatment, 83.7% reported that it would be convenient, 65.0% reported that it would cause less anxiety than an injection or infusion, 55.3% reported that it would interfere less with their everyday life, and 50.2% reported that it would reduce their symptoms more than their current psoriasis treatment (figure 5) table 3. intent to start a new once-daily oral psoriasis treatment variable category intent to start new treatment all, n = 835 (%) yes, n = 555 (%) no, n = 280 (%) treatment group apremilast 344 (41.2) 190 (34.2) 154 (55.0) tnfi 242 (29.0) 179 (32.3) 63 (22.5) ustekinumab 98 (11.7) 74 (13.3) 24 (8.6) topical therapy 98 (11.7) 68 (12.3) 30 (10.7) otc or no treatment 53 (6.3) 44 (7.9) 9 (3.2) race/ethnicity white 610 (73.1) 390 (70.3) 220 (78.6) black 114 (13.7) 95 (17.1) 19 (6.8) asian, american indian/alaska native, native hawaiian/other pacifi c islander 32 (3.8) 21 (3.8) 11 (3.9) preferred not to answer 54 (6.5) 29 (5.2) 25 (8.9) other 25 (3.0) 20 (3.6) 5 (1.8) psoriasis severity over the past week (based on a 6-point scale) none 130 (15.6) 48 (8.6) 82 (29.3) mild 308 (36.9) 197 (35.5) 111 (39.6) moderate 298 (35.7) 228 (41.1) 70 (25.0) severe 99 (11.9) 82 (14.8) 17 (6.1) otc, over the counter; tnfi, tumor necrosis factor inhibitor. figure 4. intent to start a new once-daily oral treatment, by treatment group (a), race/ ethnicity (b), and psoriasis severity over the past week (c), all p < 0.001 55.2% 74.0% 75.5% 69.4% 83.0% 0 10 20 30 40 50 60 70 80 90 100 ap re m ila st tn fi us te ki nu m ab to pi ca l t he ra py w hi te bl ac k pr ef er re d no t to a ns we r ot he r no ne mi ld mo de ra te se ve re ot c or n o tr ea tm en t as ia n, a m er ic an in di an / al as ka n at iv e, n at iv e ha wa iia n/ ot he r p ac ifi c isl an de r p at ie n ts , % 63.9% 83.3% 65.6% 53.7% 80.0% a. b. 36.9% 64.0% 76.5% 82.8% c. 0 10 20 30 40 50 60 70 80 90 100 p at ie n ts , % 0 10 20 30 40 50 60 70 80 90 100 p at ie n ts , % otc, over the counter; tnfi, tumor necrosis factor inhibitor. figure 5. views on a new once-daily oral treatment, by treatment group 0 10 20 30 40 50 60 70 80 90 100 p at ie n ts , % yes neither yes nor no no yes neither yes nor no no yes neither yes nor no no yes neither yes nor no no yes no less interference with daily life (p < 0.001) convenience of treatment (p = 0.094) less anxiety than with injection/infusion (p = 0.041) reduction in symptoms compared with current treatment (p < 0.001) intent to start new oral psoriasis treatment (p < 0.001) apremilast (n = 344) tnfi (n = 242) ustekinumab (n = 98) topical therapy/phototherapy (n = 98) tnfi, tumor necrosis factor inhibitor. • only treatment group, race/ethnicity, and psoriasis severity were statistically significant factors in the model • the following responses were examined for intent to start a new once-daily oral treatment (yes/no), by selected categories: — 83% of black respondents would start the new once-daily oral treatment • compared with white patients, the odds ratio (or) of intent to start the new treatment was 2.4 (95% confidence interval [ci], 1.4–4.2) among black respondents (p = 0.036) — intent to start the new once-daily oral treatment increased with psoriasis severity over the past week, with 76.5% of respondents with moderate psoriasis and 82.8% of respondents with severe disease answering “yes” • compared with patients with no psoriasis symptoms or signs over the past week, the or of intent to start the new treatment was 3.2 (95% ci, 2.0–4.9) among patients with mild psoriasis, 5.0 (95% ci, 3.1–8.2) among patients with moderate psoriasis, and 7.6 (95% ci, 3.9–15.0) among patients with severe psoriasis; all p < 0.001 — 79.6% of patients who responded that the new once-daily oral treatment would cause them less anxiety than an injection would start the new treatment — 87.6% of respondents who believed that the new once-daily oral treatment would reduce their symptoms more than their current treatment would start the new treatment • asked to rank characteristics of psoriasis treatment in order of importance, 58.3% of respondents ranked “extent of skin clearance” as first or second, while 43.7% ranked “route of administration” as first or second (figure 6) • laboratory monitoring was ranked least important by more than half (53.0%) of the patients figure 6. reason for treatment choice ranking 37.1 22.8 17.0 11.9 10.0 1.3 21.2 20.9 15.0 20.3 19.1 3.5 22.1 18.6 15.5 20.2 18.0 5.6 12.2 19.1 22.3 19.8 14.7 11.8 5.9 12.4 21.3 19.5 16.0 24.9 1.5 6.2 8.8 8.3 22.2 53.0 0 10 20 30 40 50 60 sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g rank 1 (p < 0.001) rank 2 (p = 0.005) rank 3 (p = 0.030) rank 4 (p = 0.233) rank 5 (p = 0.005) rank 6 (p < 0.001) p at ie n ts , % conclusions • this large, real-world study provided an account of how psoriasis impacts patients’ lives and treatment choices • patients with severe disease, black patients, and patients receiving injectable treatments were more likely to choose the new oral treatment compared with patients with mild disease, white patients, and patients receiving apremilast, respectively • willingness to start the new psoriasis treatment was common among all treatment groups • the new treatment was viewed as causing less anxiety compared with injectables across all treatment groups • extent of skin clearance and route of administration were reported as the top-ranked reasons for patients' psoriasis treatment choice • consideration of the treatment characteristics that drive the decision-making of patients with psoriasis is crucial for making effective treatment recommendations in clinical practice reference 1. feldman sr, et al. j health econ outcomes res. 2016;4:141-157. acknowledgments • this study was sponsored by bristol myers squibb • medical writing and editorial assistance was provided by tulika bhushan bahukhandi, rph, ms, of peloton advantage, llc, an open health company, and funded by bristol myers squibb disclosures • awa: has served as a research investigator, scientific advisor, and/or speaker for abbvie, almirall, arcutis biotherapeutics, aslan, beiersdorf, boehringer ingelheim/parexel, bristol myers squibb, dermavant, dermira, eli lilly, epi, incyte, leo, janssen, nimbus, novartis, ortho dermatologics, pfizer, sanofi genzyme, sun, regeneron, and ucb • ls, dd, sk, and vp: employees of and may own stock options in bristol myers squibb • nj, sr, sj, and dp: employees of open health, which received consulting fees from bristol myers squibb • dw and kb: employees of rti health solutions, which received consulting fees from bristol myers squibb scientific content on demand to request a copy of this poster: scan qr code via a barcode reader application qr codes are valid for 30 days after the congress presentation date. evaluating treatment choice among patients with moderate or severe psoriasis in the united states april w. armstrong,1 sayeli jayade,2 sanika rege,2 namita joshi,2 vardhaman patel,3 david davidson,3 samaneh kalirai,3 daniel wolin,4 kimberly boyle,4 dipen patel,2 lauren seigel3 1keck school of medicine, university of southern california, los angeles, ca; 2open health, bethesda, md; 3bristol myers squibb, princeton, nj; 4rti health solutions, research triangle park, nc presented at the 2022 fall clinical dermatology conference; october 20–23, 2022; las vegas, nv this poster may not be reproduced without written permission from the authors.email for april w. armstrong, md, mph: aprilarmstrong@post.harvard.edu synopsis • while several psoriasis treatments are available and in development, different treatment modalities are associated with varying effectiveness, risks, and economic burden, and these factors are likely to influence patients’ decisions related to their psoriasis treatment1 • this study explored the element of treatment decision-making driven by patient experiences — a cross-sectional, web-based survey captured the demographic and clinical characteristics, treatment attributes affecting therapeutic decisions, and perceptions of a new, hypothetical, once-daily oral psoriasis treatment (deucravacitinib) among patients with moderate to severe plaque psoriasis • understanding the factors that drive patients’ treatment preference is crucial for guiding clinical decision-making objectives primary • to identify factors associated with the choice of a new once-daily oral psoriasis treatment with efficacy superior to that of existing oral therapies in patients with moderate to severe psoriasis currently receiving apremilast, tumor necrosis factor inhibitors (tnfis), ustekinumab, topicals, or nonprescription treatments secondary • to rank the importance of treatment attributes to patients with moderate to severe psoriasis using apremilast, tnfis, ustekinumab, topicals, or nonprescription treatments • to elicit views on a new once-daily oral psoriasis treatment among patients with moderate to severe psoriasis using apremilast, tnfis, ustekinumab, topicals, or nonprescription treatments target product profile (deucravacitinib) • tablet formulation with once-daily dosing • clinical studies showed: — 53% of patients reported clear/mostly clear skin within 4 months — 83% of patients who reported a 75% reduction in psoriasis severity maintained this improvement at 1 year — non-serious adverse events, such as cold-like symptoms, headache, diarrhea, nausea, rash, and risk of herpes infection, led to few discontinuations • regular laboratory monitoring is not required, although pre-initiation testing may be needed • out-of-pocket costs may be similar to those of the alternative psoriasis treatments in consideration methods • a cross-sectional, web-based survey of the demographics and clinical characteristics of patients with psoriasis, their views on treatment characteristics that affect treatment-related decisions, and their perceptions of a new, hypothetical, once-daily oral psoriasis treatment • patients were assigned to predefined treatment groups: apremilast, a tnfi, ustekinumab, a topical therapy/phototherapy, and over-the-counter (otc) treatments or no treatment, based on their self-reported current treatment at the time of the survey • a hypothetical psoriasis treatment profile, described by dosage, efficacy, adverse effects, and out-of-pocket costs, was shown to the patients to elicit their views on: (1) interference with everyday life, (2) convenience, (3) treatment-related anxiety, and likelihood of initiating treatment, both (4) without a safety warning and (5) with a safety warning inclusion criteria • ≥18 years of age • residing in the united states • able to read and understand english • physician-diagnosed (self-reported) moderate or severe plaque psoriasis exclusion criteria • mild psoriasis • lack of online consent for the web-based survey data collection process • the study was reviewed and approved by an institutional review board • the study used a convenience sample of patients with moderate or severe psoriasis who were recruited by global perspectives to collect patient-reported data • patients were asked to complete an electronic patient survey that included questions from patient-reported outcome (pro) instruments and de novo questions • potential survey participants were provided with a link to the survey and completed screening questions to determine eligibility, followed by an informed consent checkbox • the final survey was administered to 882 patients statistical analysis • stepwise multivariable logistic regression was conducted to determine sociodemographic and clinical characteristics associated with the choice of the new treatment among patients who were currently receiving treatment or who had never received treatment — independent variables: treatment group, age, sex, race/ethnicity, psoriasis severity over the past week, comorbidities, disease and treatment duration, presence of psoriatic arthritis (psa) at baseline, number of flares, and number of body regions affected • treatment attributes (route of administration, extent of skin clearance, laboratory monitoring, durability, safety, and dosing frequency) were ranked as an ordinal category (scale of 1–6) by patients • chi-square test was conducted to detect significant differences between patient rankings of each treatment attribute and to assess the variations in patient views on the new oral treatment results • figure 1 shows the responses of the 5 baseline treatment groups surveyed • the study sample included 882 patients (mean age = 45.7 [±12.8] years); the majority were female (67.7%), most were white (74.9%), and their average duration of time since psoriasis diagnosis was 14.9 (±11.8) years (figures 2 and 3; table 1) • of 882 patients, 818 (92.8%) were currently receiving treatment and had been on their current treatment for a mean of 2.9 (±4.8) years (table 2) • with their current treatment regimen, 50.8% of patients in the total study population described their psoriasis over the past week as mild, very mild, or none, while 36.5% reported it as moderate and 12.7% reported it as severe or very severe (table 2) figure 1. targeted baseline treatment groups 344 242 98 98 100 0 50 100 150 200 250 300 350 400 p at ie n ts w h o c o m p le te d s u rv e y, n treatment group group 1: apremilast group 2: tnfi group 3: ustekinumab group 4: topical/phototherapy group 5: exploratorya athe exploratory group included patients who were using nonprescription treatments (n = 36), patients who had never received treatment (n = 17), and patients who had received treatment in the past but were not currently receiving treatment (n = 47). tnfi, tumor necrosis factor inhibitor. figure 2. key baseline characteristics, by sex (a) and race/ethnicitya (b) 74.9% 14.1% 2% 2% 0.2% 2.4% 6.1% white black american indian/ alaska native asian native hawaiian/ other pacific islander other preferred not to answer b.a. male female preferred not to answer 32.0% 67.7% 0.3% apercentages sum to >100% because respondents could select multiple races/ethnicities, as applicable. figure 3. key baseline characteristics for all respondents by insurance typea 13.6% 11.9% 54.5% 21.1% 2.2% 3.4% medicare medicaid employer-sponsored private insurance individually purchased private insurance uninsured military/veterans' coverage apercentages sum to >100% because respondents could select more than 1 insurance type, as applicable. table 1. key baseline characteristics for all respondents by patient age category all respondents (n = 882) mean 45.71 median (q1–q3) 45 range 18–76 q1–q3, quartiles 1–3. table 2. key baseline clinical characteristics parameter statistic or category all respondents, n = 882 (%) treatment status, n (%) currently receiving treatment 818 (92.8) was receiving treatment but has stopped 47 (5.3) never received treatment 17 (1.9) treatment duration, years mean (sd) 2.86 (4.81) median (q1–q3) 1.0 (0.0–3.0) range 0.0–42.0 current treatment type, n (%) over-the-counter nonprescription 225 (27.5) topical prescription steroid 230 (28.1) topical vitamin d analog 49 (6.0) other topical treatment 55 (6.7) ultraviolet light/phototherapy 51 (6.2) apremilast 356 (43.5) ustekinumab 101 (12.3) tnfi treatment 251 (30.7) psoriasis severity over the past week, n (%) none 31 (14.8) very mild 155 (17.6) mild 162 (18.4) moderate 322 (36.5) severe 86 (9.8) very severe 26 (2.9) bsa, body surface area; q1–q3, quartiles 1–3; sd, standard deviation; tnfi, tumor necrosis factor inhibitor. • among patients who were currently receiving treatment or who had never received treatment (n = 835), apremilast (41.2%) and tnfis (29.0%) were the most commonly used treatments, and otc or no treatment was the least common group (6.3%) (table 3) • of patients who had never received treatment, 88.2% expressed intent to start the new oral psoriasis treatment, compared with 80.6% of patients who used nonprescription otc treatment, 75.5% of patients who used ustekinumab, 74.0% of patients who used a tnfi, 69.4% of patients who used topical therapy, and 55.2% of patients who used apremilast (figure 4) • willingness to start the new, once-daily oral treatment was high across all groups, including patients currently using apremilast • in response to questions about the new treatment, 83.7% reported that it would be convenient, 65.0% reported that it would cause less anxiety than an injection or infusion, 55.3% reported that it would interfere less with their everyday life, and 50.2% reported that it would reduce their symptoms more than their current psoriasis treatment (figure 5) table 3. intent to start a new once-daily oral psoriasis treatment variable category intent to start new treatment all, n = 835 (%) yes, n = 555 (%) no, n = 280 (%) treatment group apremilast 344 (41.2) 190 (34.2) 154 (55.0) tnfi 242 (29.0) 179 (32.3) 63 (22.5) ustekinumab 98 (11.7) 74 (13.3) 24 (8.6) topical therapy 98 (11.7) 68 (12.3) 30 (10.7) otc or no treatment 53 (6.3) 44 (7.9) 9 (3.2) race/ethnicity white 610 (73.1) 390 (70.3) 220 (78.6) black 114 (13.7) 95 (17.1) 19 (6.8) asian, american indian/alaska native, native hawaiian/other pacifi c islander 32 (3.8) 21 (3.8) 11 (3.9) preferred not to answer 54 (6.5) 29 (5.2) 25 (8.9) other 25 (3.0) 20 (3.6) 5 (1.8) psoriasis severity over the past week (based on a 6-point scale) none 130 (15.6) 48 (8.6) 82 (29.3) mild 308 (36.9) 197 (35.5) 111 (39.6) moderate 298 (35.7) 228 (41.1) 70 (25.0) severe 99 (11.9) 82 (14.8) 17 (6.1) otc, over the counter; tnfi, tumor necrosis factor inhibitor. figure 4. intent to start a new once-daily oral treatment, by treatment group (a), race/ ethnicity (b), and psoriasis severity over the past week (c), all p < 0.001 55.2% 74.0% 75.5% 69.4% 83.0% 0 10 20 30 40 50 60 70 80 90 100 ap re m ila st tn fi us te ki nu m ab to pi ca l t he ra py w hi te bl ac k pr ef er re d no t to a ns we r ot he r no ne mi ld mo de ra te se ve re ot c or n o tr ea tm en t as ia n, a m er ic an in di an / al as ka n at iv e, n at iv e ha wa iia n/ ot he r p ac ifi c isl an de r p at ie n ts , % 63.9% 83.3% 65.6% 53.7% 80.0% a. b. 36.9% 64.0% 76.5% 82.8% c. 0 10 20 30 40 50 60 70 80 90 100 p at ie n ts , % 0 10 20 30 40 50 60 70 80 90 100 p at ie n ts , % otc, over the counter; tnfi, tumor necrosis factor inhibitor. figure 5. views on a new once-daily oral treatment, by treatment group 0 10 20 30 40 50 60 70 80 90 100 p at ie n ts , % yes neither yes nor no no yes neither yes nor no no yes neither yes nor no no yes neither yes nor no no yes no less interference with daily life (p < 0.001) convenience of treatment (p = 0.094) less anxiety than with injection/infusion (p = 0.041) reduction in symptoms compared with current treatment (p < 0.001) intent to start new oral psoriasis treatment (p < 0.001) apremilast (n = 344) tnfi (n = 242) ustekinumab (n = 98) topical therapy/phototherapy (n = 98) tnfi, tumor necrosis factor inhibitor. • only treatment group, race/ethnicity, and psoriasis severity were statistically significant factors in the model • the following responses were examined for intent to start a new once-daily oral treatment (yes/no), by selected categories: — 83% of black respondents would start the new once-daily oral treatment • compared with white patients, the odds ratio (or) of intent to start the new treatment was 2.4 (95% confidence interval [ci], 1.4–4.2) among black respondents (p = 0.036) — intent to start the new once-daily oral treatment increased with psoriasis severity over the past week, with 76.5% of respondents with moderate psoriasis and 82.8% of respondents with severe disease answering “yes” • compared with patients with no psoriasis symptoms or signs over the past week, the or of intent to start the new treatment was 3.2 (95% ci, 2.0–4.9) among patients with mild psoriasis, 5.0 (95% ci, 3.1–8.2) among patients with moderate psoriasis, and 7.6 (95% ci, 3.9–15.0) among patients with severe psoriasis; all p < 0.001 — 79.6% of patients who responded that the new once-daily oral treatment would cause them less anxiety than an injection would start the new treatment — 87.6% of respondents who believed that the new once-daily oral treatment would reduce their symptoms more than their current treatment would start the new treatment • asked to rank characteristics of psoriasis treatment in order of importance, 58.3% of respondents ranked “extent of skin clearance” as first or second, while 43.7% ranked “route of administration” as first or second (figure 6) • laboratory monitoring was ranked least important by more than half (53.0%) of the patients figure 6. reason for treatment choice ranking 37.1 22.8 17.0 11.9 10.0 1.3 21.2 20.9 15.0 20.3 19.1 3.5 22.1 18.6 15.5 20.2 18.0 5.6 12.2 19.1 22.3 19.8 14.7 11.8 5.9 12.4 21.3 19.5 16.0 24.9 1.5 6.2 8.8 8.3 22.2 53.0 0 10 20 30 40 50 60 sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g rank 1 (p < 0.001) rank 2 (p = 0.005) rank 3 (p = 0.030) rank 4 (p = 0.233) rank 5 (p = 0.005) rank 6 (p < 0.001) p at ie n ts , % conclusions • this large, real-world study provided an account of how psoriasis impacts patients’ lives and treatment choices • patients with severe disease, black patients, and patients receiving injectable treatments were more likely to choose the new oral treatment compared with patients with mild disease, white patients, and patients receiving apremilast, respectively • willingness to start the new psoriasis treatment was common among all treatment groups • the new treatment was viewed as causing less anxiety compared with injectables across all treatment groups • extent of skin clearance and route of administration were reported as the top-ranked reasons for patients' psoriasis treatment choice • consideration of the treatment characteristics that drive the decision-making of patients with psoriasis is crucial for making effective treatment recommendations in clinical practice reference 1. feldman sr, et al. j health econ outcomes res. 2016;4:141-157. acknowledgments • this study was sponsored by bristol myers squibb • medical writing and editorial assistance was provided by tulika bhushan bahukhandi, rph, ms, of peloton advantage, llc, an open health company, and funded by bristol myers squibb disclosures • awa: has served as a research investigator, scientific advisor, and/or speaker for abbvie, almirall, arcutis biotherapeutics, aslan, beiersdorf, boehringer ingelheim/parexel, bristol myers squibb, dermavant, dermira, eli lilly, epi, incyte, leo, janssen, nimbus, novartis, ortho dermatologics, pfizer, sanofi genzyme, sun, regeneron, and ucb • ls, dd, sk, and vp: employees of and may own stock options in bristol myers squibb • nj, sr, sj, and dp: employees of open health, which received consulting fees from bristol myers squibb • dw and kb: employees of rti health solutions, which received consulting fees from bristol myers squibb scientific content on demand to request a copy of this poster: scan qr code via a barcode reader application qr codes are valid for 30 days after the congress presentation date. evaluating treatment choice among patients with moderate or severe psoriasis in the united states april w. armstrong,1 sayeli jayade,2 sanika rege,2 namita joshi,2 vardhaman patel,3 david davidson,3 samaneh kalirai,3 daniel wolin,4 kimberly boyle,4 dipen patel,2 lauren seigel3 1keck school of medicine, university of southern california, los angeles, ca; 2open health, bethesda, md; 3bristol myers squibb, princeton, nj; 4rti health solutions, research triangle park, nc presented at the 2022 fall clinical dermatology conference; october 20–23, 2022; las vegas, nv this poster may not be reproduced without written permission from the authors.email for april w. armstrong, md, mph: aprilarmstrong@post.harvard.edu synopsis • while several psoriasis treatments are available and in development, different treatment modalities are associated with varying effectiveness, risks, and economic burden, and these factors are likely to influence patients’ decisions related to their psoriasis treatment1 • this study explored the element of treatment decision-making driven by patient experiences — a cross-sectional, web-based survey captured the demographic and clinical characteristics, treatment attributes affecting therapeutic decisions, and perceptions of a new, hypothetical, once-daily oral psoriasis treatment (deucravacitinib) among patients with moderate to severe plaque psoriasis • understanding the factors that drive patients’ treatment preference is crucial for guiding clinical decision-making objectives primary • to identify factors associated with the choice of a new once-daily oral psoriasis treatment with efficacy superior to that of existing oral therapies in patients with moderate to severe psoriasis currently receiving apremilast, tumor necrosis factor inhibitors (tnfis), ustekinumab, topicals, or nonprescription treatments secondary • to rank the importance of treatment attributes to patients with moderate to severe psoriasis using apremilast, tnfis, ustekinumab, topicals, or nonprescription treatments • to elicit views on a new once-daily oral psoriasis treatment among patients with moderate to severe psoriasis using apremilast, tnfis, ustekinumab, topicals, or nonprescription treatments target product profile (deucravacitinib) • tablet formulation with once-daily dosing • clinical studies showed: — 53% of patients reported clear/mostly clear skin within 4 months — 83% of patients who reported a 75% reduction in psoriasis severity maintained this improvement at 1 year — non-serious adverse events, such as cold-like symptoms, headache, diarrhea, nausea, rash, and risk of herpes infection, led to few discontinuations • regular laboratory monitoring is not required, although pre-initiation testing may be needed • out-of-pocket costs may be similar to those of the alternative psoriasis treatments in consideration methods • a cross-sectional, web-based survey of the demographics and clinical characteristics of patients with psoriasis, their views on treatment characteristics that affect treatment-related decisions, and their perceptions of a new, hypothetical, once-daily oral psoriasis treatment • patients were assigned to predefined treatment groups: apremilast, a tnfi, ustekinumab, a topical therapy/phototherapy, and over-the-counter (otc) treatments or no treatment, based on their self-reported current treatment at the time of the survey • a hypothetical psoriasis treatment profile, described by dosage, efficacy, adverse effects, and out-of-pocket costs, was shown to the patients to elicit their views on: (1) interference with everyday life, (2) convenience, (3) treatment-related anxiety, and likelihood of initiating treatment, both (4) without a safety warning and (5) with a safety warning inclusion criteria • ≥18 years of age • residing in the united states • able to read and understand english • physician-diagnosed (self-reported) moderate or severe plaque psoriasis exclusion criteria • mild psoriasis • lack of online consent for the web-based survey data collection process • the study was reviewed and approved by an institutional review board • the study used a convenience sample of patients with moderate or severe psoriasis who were recruited by global perspectives to collect patient-reported data • patients were asked to complete an electronic patient survey that included questions from patient-reported outcome (pro) instruments and de novo questions • potential survey participants were provided with a link to the survey and completed screening questions to determine eligibility, followed by an informed consent checkbox • the final survey was administered to 882 patients statistical analysis • stepwise multivariable logistic regression was conducted to determine sociodemographic and clinical characteristics associated with the choice of the new treatment among patients who were currently receiving treatment or who had never received treatment — independent variables: treatment group, age, sex, race/ethnicity, psoriasis severity over the past week, comorbidities, disease and treatment duration, presence of psoriatic arthritis (psa) at baseline, number of flares, and number of body regions affected • treatment attributes (route of administration, extent of skin clearance, laboratory monitoring, durability, safety, and dosing frequency) were ranked as an ordinal category (scale of 1–6) by patients • chi-square test was conducted to detect significant differences between patient rankings of each treatment attribute and to assess the variations in patient views on the new oral treatment results • figure 1 shows the responses of the 5 baseline treatment groups surveyed • the study sample included 882 patients (mean age = 45.7 [±12.8] years); the majority were female (67.7%), most were white (74.9%), and their average duration of time since psoriasis diagnosis was 14.9 (±11.8) years (figures 2 and 3; table 1) • of 882 patients, 818 (92.8%) were currently receiving treatment and had been on their current treatment for a mean of 2.9 (±4.8) years (table 2) • with their current treatment regimen, 50.8% of patients in the total study population described their psoriasis over the past week as mild, very mild, or none, while 36.5% reported it as moderate and 12.7% reported it as severe or very severe (table 2) figure 1. targeted baseline treatment groups 344 242 98 98 100 0 50 100 150 200 250 300 350 400 p at ie n ts w h o c o m p le te d s u rv e y, n treatment group group 1: apremilast group 2: tnfi group 3: ustekinumab group 4: topical/phototherapy group 5: exploratorya athe exploratory group included patients who were using nonprescription treatments (n = 36), patients who had never received treatment (n = 17), and patients who had received treatment in the past but were not currently receiving treatment (n = 47). tnfi, tumor necrosis factor inhibitor. figure 2. key baseline characteristics, by sex (a) and race/ethnicitya (b) 74.9% 14.1% 2% 2% 0.2% 2.4% 6.1% white black american indian/ alaska native asian native hawaiian/ other pacific islander other preferred not to answer b.a. male female preferred not to answer 32.0% 67.7% 0.3% apercentages sum to >100% because respondents could select multiple races/ethnicities, as applicable. figure 3. key baseline characteristics for all respondents by insurance typea 13.6% 11.9% 54.5% 21.1% 2.2% 3.4% medicare medicaid employer-sponsored private insurance individually purchased private insurance uninsured military/veterans' coverage apercentages sum to >100% because respondents could select more than 1 insurance type, as applicable. table 1. key baseline characteristics for all respondents by patient age category all respondents (n = 882) mean 45.71 median (q1–q3) 45 range 18–76 q1–q3, quartiles 1–3. table 2. key baseline clinical characteristics parameter statistic or category all respondents, n = 882 (%) treatment status, n (%) currently receiving treatment 818 (92.8) was receiving treatment but has stopped 47 (5.3) never received treatment 17 (1.9) treatment duration, years mean (sd) 2.86 (4.81) median (q1–q3) 1.0 (0.0–3.0) range 0.0–42.0 current treatment type, n (%) over-the-counter nonprescription 225 (27.5) topical prescription steroid 230 (28.1) topical vitamin d analog 49 (6.0) other topical treatment 55 (6.7) ultraviolet light/phototherapy 51 (6.2) apremilast 356 (43.5) ustekinumab 101 (12.3) tnfi treatment 251 (30.7) psoriasis severity over the past week, n (%) none 31 (14.8) very mild 155 (17.6) mild 162 (18.4) moderate 322 (36.5) severe 86 (9.8) very severe 26 (2.9) bsa, body surface area; q1–q3, quartiles 1–3; sd, standard deviation; tnfi, tumor necrosis factor inhibitor. • among patients who were currently receiving treatment or who had never received treatment (n = 835), apremilast (41.2%) and tnfis (29.0%) were the most commonly used treatments, and otc or no treatment was the least common group (6.3%) (table 3) • of patients who had never received treatment, 88.2% expressed intent to start the new oral psoriasis treatment, compared with 80.6% of patients who used nonprescription otc treatment, 75.5% of patients who used ustekinumab, 74.0% of patients who used a tnfi, 69.4% of patients who used topical therapy, and 55.2% of patients who used apremilast (figure 4) • willingness to start the new, once-daily oral treatment was high across all groups, including patients currently using apremilast • in response to questions about the new treatment, 83.7% reported that it would be convenient, 65.0% reported that it would cause less anxiety than an injection or infusion, 55.3% reported that it would interfere less with their everyday life, and 50.2% reported that it would reduce their symptoms more than their current psoriasis treatment (figure 5) table 3. intent to start a new once-daily oral psoriasis treatment variable category intent to start new treatment all, n = 835 (%) yes, n = 555 (%) no, n = 280 (%) treatment group apremilast 344 (41.2) 190 (34.2) 154 (55.0) tnfi 242 (29.0) 179 (32.3) 63 (22.5) ustekinumab 98 (11.7) 74 (13.3) 24 (8.6) topical therapy 98 (11.7) 68 (12.3) 30 (10.7) otc or no treatment 53 (6.3) 44 (7.9) 9 (3.2) race/ethnicity white 610 (73.1) 390 (70.3) 220 (78.6) black 114 (13.7) 95 (17.1) 19 (6.8) asian, american indian/alaska native, native hawaiian/other pacifi c islander 32 (3.8) 21 (3.8) 11 (3.9) preferred not to answer 54 (6.5) 29 (5.2) 25 (8.9) other 25 (3.0) 20 (3.6) 5 (1.8) psoriasis severity over the past week (based on a 6-point scale) none 130 (15.6) 48 (8.6) 82 (29.3) mild 308 (36.9) 197 (35.5) 111 (39.6) moderate 298 (35.7) 228 (41.1) 70 (25.0) severe 99 (11.9) 82 (14.8) 17 (6.1) otc, over the counter; tnfi, tumor necrosis factor inhibitor. figure 4. intent to start a new once-daily oral treatment, by treatment group (a), race/ ethnicity (b), and psoriasis severity over the past week (c), all p < 0.001 55.2% 74.0% 75.5% 69.4% 83.0% 0 10 20 30 40 50 60 70 80 90 100 ap re m ila st tn fi us te ki nu m ab to pi ca l t he ra py w hi te bl ac k pr ef er re d no t to a ns we r ot he r no ne mi ld mo de ra te se ve re ot c or n o tr ea tm en t as ia n, a m er ic an in di an / al as ka n at iv e, n at iv e ha wa iia n/ ot he r p ac ifi c isl an de r p at ie n ts , % 63.9% 83.3% 65.6% 53.7% 80.0% a. b. 36.9% 64.0% 76.5% 82.8% c. 0 10 20 30 40 50 60 70 80 90 100 p at ie n ts , % 0 10 20 30 40 50 60 70 80 90 100 p at ie n ts , % otc, over the counter; tnfi, tumor necrosis factor inhibitor. figure 5. views on a new once-daily oral treatment, by treatment group 0 10 20 30 40 50 60 70 80 90 100 p at ie n ts , % yes neither yes nor no no yes neither yes nor no no yes neither yes nor no no yes neither yes nor no no yes no less interference with daily life (p < 0.001) convenience of treatment (p = 0.094) less anxiety than with injection/infusion (p = 0.041) reduction in symptoms compared with current treatment (p < 0.001) intent to start new oral psoriasis treatment (p < 0.001) apremilast (n = 344) tnfi (n = 242) ustekinumab (n = 98) topical therapy/phototherapy (n = 98) tnfi, tumor necrosis factor inhibitor. • only treatment group, race/ethnicity, and psoriasis severity were statistically significant factors in the model • the following responses were examined for intent to start a new once-daily oral treatment (yes/no), by selected categories: — 83% of black respondents would start the new once-daily oral treatment • compared with white patients, the odds ratio (or) of intent to start the new treatment was 2.4 (95% confidence interval [ci], 1.4–4.2) among black respondents (p = 0.036) — intent to start the new once-daily oral treatment increased with psoriasis severity over the past week, with 76.5% of respondents with moderate psoriasis and 82.8% of respondents with severe disease answering “yes” • compared with patients with no psoriasis symptoms or signs over the past week, the or of intent to start the new treatment was 3.2 (95% ci, 2.0–4.9) among patients with mild psoriasis, 5.0 (95% ci, 3.1–8.2) among patients with moderate psoriasis, and 7.6 (95% ci, 3.9–15.0) among patients with severe psoriasis; all p < 0.001 — 79.6% of patients who responded that the new once-daily oral treatment would cause them less anxiety than an injection would start the new treatment — 87.6% of respondents who believed that the new once-daily oral treatment would reduce their symptoms more than their current treatment would start the new treatment • asked to rank characteristics of psoriasis treatment in order of importance, 58.3% of respondents ranked “extent of skin clearance” as first or second, while 43.7% ranked “route of administration” as first or second (figure 6) • laboratory monitoring was ranked least important by more than half (53.0%) of the patients figure 6. reason for treatment choice ranking 37.1 22.8 17.0 11.9 10.0 1.3 21.2 20.9 15.0 20.3 19.1 3.5 22.1 18.6 15.5 20.2 18.0 5.6 12.2 19.1 22.3 19.8 14.7 11.8 5.9 12.4 21.3 19.5 16.0 24.9 1.5 6.2 8.8 8.3 22.2 53.0 0 10 20 30 40 50 60 sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g rank 1 (p < 0.001) rank 2 (p = 0.005) rank 3 (p = 0.030) rank 4 (p = 0.233) rank 5 (p = 0.005) rank 6 (p < 0.001) p at ie n ts , % conclusions • this large, real-world study provided an account of how psoriasis impacts patients’ lives and treatment choices • patients with severe disease, black patients, and patients receiving injectable treatments were more likely to choose the new oral treatment compared with patients with mild disease, white patients, and patients receiving apremilast, respectively • willingness to start the new psoriasis treatment was common among all treatment groups • the new treatment was viewed as causing less anxiety compared with injectables across all treatment groups • extent of skin clearance and route of administration were reported as the top-ranked reasons for patients' psoriasis treatment choice • consideration of the treatment characteristics that drive the decision-making of patients with psoriasis is crucial for making effective treatment recommendations in clinical practice reference 1. feldman sr, et al. j health econ outcomes res. 2016;4:141-157. acknowledgments • this study was sponsored by bristol myers squibb • medical writing and editorial assistance was provided by tulika bhushan bahukhandi, rph, ms, of peloton advantage, llc, an open health company, and funded by bristol myers squibb disclosures • awa: has served as a research investigator, scientific advisor, and/or speaker for abbvie, almirall, arcutis biotherapeutics, aslan, beiersdorf, boehringer ingelheim/parexel, bristol myers squibb, dermavant, dermira, eli lilly, epi, incyte, leo, janssen, nimbus, novartis, ortho dermatologics, pfizer, sanofi genzyme, sun, regeneron, and ucb • ls, dd, sk, and vp: employees of and may own stock options in bristol myers squibb • nj, sr, sj, and dp: employees of open health, which received consulting fees from bristol myers squibb • dw and kb: employees of rti health solutions, which received consulting fees from bristol myers squibb scientific content on demand to request a copy of this poster: scan qr code via a barcode reader application qr codes are valid for 30 days after the congress presentation date. evaluating treatment choice among patients with moderate or severe psoriasis in the united states april w. armstrong,1 sayeli jayade,2 sanika rege,2 namita joshi,2 vardhaman patel,3 david davidson,3 samaneh kalirai,3 daniel wolin,4 kimberly boyle,4 dipen patel,2 lauren seigel3 1keck school of medicine, university of southern california, los angeles, ca; 2open health, bethesda, md; 3bristol myers squibb, princeton, nj; 4rti health solutions, research triangle park, nc presented at the 2022 fall clinical dermatology conference; october 20–23, 2022; las vegas, nv this poster may not be reproduced without written permission from the authors.email for april w. armstrong, md, mph: aprilarmstrong@post.harvard.edu synopsis • while several psoriasis treatments are available and in development, different treatment modalities are associated with varying effectiveness, risks, and economic burden, and these factors are likely to influence patients’ decisions related to their psoriasis treatment1 • this study explored the element of treatment decision-making driven by patient experiences — a cross-sectional, web-based survey captured the demographic and clinical characteristics, treatment attributes affecting therapeutic decisions, and perceptions of a new, hypothetical, once-daily oral psoriasis treatment (deucravacitinib) among patients with moderate to severe plaque psoriasis • understanding the factors that drive patients’ treatment preference is crucial for guiding clinical decision-making objectives primary • to identify factors associated with the choice of a new once-daily oral psoriasis treatment with efficacy superior to that of existing oral therapies in patients with moderate to severe psoriasis currently receiving apremilast, tumor necrosis factor inhibitors (tnfis), ustekinumab, topicals, or nonprescription treatments secondary • to rank the importance of treatment attributes to patients with moderate to severe psoriasis using apremilast, tnfis, ustekinumab, topicals, or nonprescription treatments • to elicit views on a new once-daily oral psoriasis treatment among patients with moderate to severe psoriasis using apremilast, tnfis, ustekinumab, topicals, or nonprescription treatments target product profile (deucravacitinib) • tablet formulation with once-daily dosing • clinical studies showed: — 53% of patients reported clear/mostly clear skin within 4 months — 83% of patients who reported a 75% reduction in psoriasis severity maintained this improvement at 1 year — non-serious adverse events, such as cold-like symptoms, headache, diarrhea, nausea, rash, and risk of herpes infection, led to few discontinuations • regular laboratory monitoring is not required, although pre-initiation testing may be needed • out-of-pocket costs may be similar to those of the alternative psoriasis treatments in consideration methods • a cross-sectional, web-based survey of the demographics and clinical characteristics of patients with psoriasis, their views on treatment characteristics that affect treatment-related decisions, and their perceptions of a new, hypothetical, once-daily oral psoriasis treatment • patients were assigned to predefined treatment groups: apremilast, a tnfi, ustekinumab, a topical therapy/phototherapy, and over-the-counter (otc) treatments or no treatment, based on their self-reported current treatment at the time of the survey • a hypothetical psoriasis treatment profile, described by dosage, efficacy, adverse effects, and out-of-pocket costs, was shown to the patients to elicit their views on: (1) interference with everyday life, (2) convenience, (3) treatment-related anxiety, and likelihood of initiating treatment, both (4) without a safety warning and (5) with a safety warning inclusion criteria • ≥18 years of age • residing in the united states • able to read and understand english • physician-diagnosed (self-reported) moderate or severe plaque psoriasis exclusion criteria • mild psoriasis • lack of online consent for the web-based survey data collection process • the study was reviewed and approved by an institutional review board • the study used a convenience sample of patients with moderate or severe psoriasis who were recruited by global perspectives to collect patient-reported data • patients were asked to complete an electronic patient survey that included questions from patient-reported outcome (pro) instruments and de novo questions • potential survey participants were provided with a link to the survey and completed screening questions to determine eligibility, followed by an informed consent checkbox • the final survey was administered to 882 patients statistical analysis • stepwise multivariable logistic regression was conducted to determine sociodemographic and clinical characteristics associated with the choice of the new treatment among patients who were currently receiving treatment or who had never received treatment — independent variables: treatment group, age, sex, race/ethnicity, psoriasis severity over the past week, comorbidities, disease and treatment duration, presence of psoriatic arthritis (psa) at baseline, number of flares, and number of body regions affected • treatment attributes (route of administration, extent of skin clearance, laboratory monitoring, durability, safety, and dosing frequency) were ranked as an ordinal category (scale of 1–6) by patients • chi-square test was conducted to detect significant differences between patient rankings of each treatment attribute and to assess the variations in patient views on the new oral treatment results • figure 1 shows the responses of the 5 baseline treatment groups surveyed • the study sample included 882 patients (mean age = 45.7 [±12.8] years); the majority were female (67.7%), most were white (74.9%), and their average duration of time since psoriasis diagnosis was 14.9 (±11.8) years (figures 2 and 3; table 1) • of 882 patients, 818 (92.8%) were currently receiving treatment and had been on their current treatment for a mean of 2.9 (±4.8) years (table 2) • with their current treatment regimen, 50.8% of patients in the total study population described their psoriasis over the past week as mild, very mild, or none, while 36.5% reported it as moderate and 12.7% reported it as severe or very severe (table 2) figure 1. targeted baseline treatment groups 344 242 98 98 100 0 50 100 150 200 250 300 350 400 p at ie n ts w h o c o m p le te d s u rv e y, n treatment group group 1: apremilast group 2: tnfi group 3: ustekinumab group 4: topical/phototherapy group 5: exploratorya athe exploratory group included patients who were using nonprescription treatments (n = 36), patients who had never received treatment (n = 17), and patients who had received treatment in the past but were not currently receiving treatment (n = 47). tnfi, tumor necrosis factor inhibitor. figure 2. key baseline characteristics, by sex (a) and race/ethnicitya (b) 74.9% 14.1% 2% 2% 0.2% 2.4% 6.1% white black american indian/ alaska native asian native hawaiian/ other pacific islander other preferred not to answer b.a. male female preferred not to answer 32.0% 67.7% 0.3% apercentages sum to >100% because respondents could select multiple races/ethnicities, as applicable. figure 3. key baseline characteristics for all respondents by insurance typea 13.6% 11.9% 54.5% 21.1% 2.2% 3.4% medicare medicaid employer-sponsored private insurance individually purchased private insurance uninsured military/veterans' coverage apercentages sum to >100% because respondents could select more than 1 insurance type, as applicable. table 1. key baseline characteristics for all respondents by patient age category all respondents (n = 882) mean 45.71 median (q1–q3) 45 range 18–76 q1–q3, quartiles 1–3. table 2. key baseline clinical characteristics parameter statistic or category all respondents, n = 882 (%) treatment status, n (%) currently receiving treatment 818 (92.8) was receiving treatment but has stopped 47 (5.3) never received treatment 17 (1.9) treatment duration, years mean (sd) 2.86 (4.81) median (q1–q3) 1.0 (0.0–3.0) range 0.0–42.0 current treatment type, n (%) over-the-counter nonprescription 225 (27.5) topical prescription steroid 230 (28.1) topical vitamin d analog 49 (6.0) other topical treatment 55 (6.7) ultraviolet light/phototherapy 51 (6.2) apremilast 356 (43.5) ustekinumab 101 (12.3) tnfi treatment 251 (30.7) psoriasis severity over the past week, n (%) none 31 (14.8) very mild 155 (17.6) mild 162 (18.4) moderate 322 (36.5) severe 86 (9.8) very severe 26 (2.9) bsa, body surface area; q1–q3, quartiles 1–3; sd, standard deviation; tnfi, tumor necrosis factor inhibitor. • among patients who were currently receiving treatment or who had never received treatment (n = 835), apremilast (41.2%) and tnfis (29.0%) were the most commonly used treatments, and otc or no treatment was the least common group (6.3%) (table 3) • of patients who had never received treatment, 88.2% expressed intent to start the new oral psoriasis treatment, compared with 80.6% of patients who used nonprescription otc treatment, 75.5% of patients who used ustekinumab, 74.0% of patients who used a tnfi, 69.4% of patients who used topical therapy, and 55.2% of patients who used apremilast (figure 4) • willingness to start the new, once-daily oral treatment was high across all groups, including patients currently using apremilast • in response to questions about the new treatment, 83.7% reported that it would be convenient, 65.0% reported that it would cause less anxiety than an injection or infusion, 55.3% reported that it would interfere less with their everyday life, and 50.2% reported that it would reduce their symptoms more than their current psoriasis treatment (figure 5) table 3. intent to start a new once-daily oral psoriasis treatment variable category intent to start new treatment all, n = 835 (%) yes, n = 555 (%) no, n = 280 (%) treatment group apremilast 344 (41.2) 190 (34.2) 154 (55.0) tnfi 242 (29.0) 179 (32.3) 63 (22.5) ustekinumab 98 (11.7) 74 (13.3) 24 (8.6) topical therapy 98 (11.7) 68 (12.3) 30 (10.7) otc or no treatment 53 (6.3) 44 (7.9) 9 (3.2) race/ethnicity white 610 (73.1) 390 (70.3) 220 (78.6) black 114 (13.7) 95 (17.1) 19 (6.8) asian, american indian/alaska native, native hawaiian/other pacifi c islander 32 (3.8) 21 (3.8) 11 (3.9) preferred not to answer 54 (6.5) 29 (5.2) 25 (8.9) other 25 (3.0) 20 (3.6) 5 (1.8) psoriasis severity over the past week (based on a 6-point scale) none 130 (15.6) 48 (8.6) 82 (29.3) mild 308 (36.9) 197 (35.5) 111 (39.6) moderate 298 (35.7) 228 (41.1) 70 (25.0) severe 99 (11.9) 82 (14.8) 17 (6.1) otc, over the counter; tnfi, tumor necrosis factor inhibitor. figure 4. intent to start a new once-daily oral treatment, by treatment group (a), race/ ethnicity (b), and psoriasis severity over the past week (c), all p < 0.001 55.2% 74.0% 75.5% 69.4% 83.0% 0 10 20 30 40 50 60 70 80 90 100 ap re m ila st tn fi us te ki nu m ab to pi ca l t he ra py w hi te bl ac k pr ef er re d no t to a ns we r ot he r no ne mi ld mo de ra te se ve re ot c or n o tr ea tm en t as ia n, a m er ic an in di an / al as ka n at iv e, n at iv e ha wa iia n/ ot he r p ac ifi c isl an de r p at ie n ts , % 63.9% 83.3% 65.6% 53.7% 80.0% a. b. 36.9% 64.0% 76.5% 82.8% c. 0 10 20 30 40 50 60 70 80 90 100 p at ie n ts , % 0 10 20 30 40 50 60 70 80 90 100 p at ie n ts , % otc, over the counter; tnfi, tumor necrosis factor inhibitor. figure 5. views on a new once-daily oral treatment, by treatment group 0 10 20 30 40 50 60 70 80 90 100 p at ie n ts , % yes neither yes nor no no yes neither yes nor no no yes neither yes nor no no yes neither yes nor no no yes no less interference with daily life (p < 0.001) convenience of treatment (p = 0.094) less anxiety than with injection/infusion (p = 0.041) reduction in symptoms compared with current treatment (p < 0.001) intent to start new oral psoriasis treatment (p < 0.001) apremilast (n = 344) tnfi (n = 242) ustekinumab (n = 98) topical therapy/phototherapy (n = 98) tnfi, tumor necrosis factor inhibitor. • only treatment group, race/ethnicity, and psoriasis severity were statistically significant factors in the model • the following responses were examined for intent to start a new once-daily oral treatment (yes/no), by selected categories: — 83% of black respondents would start the new once-daily oral treatment • compared with white patients, the odds ratio (or) of intent to start the new treatment was 2.4 (95% confidence interval [ci], 1.4–4.2) among black respondents (p = 0.036) — intent to start the new once-daily oral treatment increased with psoriasis severity over the past week, with 76.5% of respondents with moderate psoriasis and 82.8% of respondents with severe disease answering “yes” • compared with patients with no psoriasis symptoms or signs over the past week, the or of intent to start the new treatment was 3.2 (95% ci, 2.0–4.9) among patients with mild psoriasis, 5.0 (95% ci, 3.1–8.2) among patients with moderate psoriasis, and 7.6 (95% ci, 3.9–15.0) among patients with severe psoriasis; all p < 0.001 — 79.6% of patients who responded that the new once-daily oral treatment would cause them less anxiety than an injection would start the new treatment — 87.6% of respondents who believed that the new once-daily oral treatment would reduce their symptoms more than their current treatment would start the new treatment • asked to rank characteristics of psoriasis treatment in order of importance, 58.3% of respondents ranked “extent of skin clearance” as first or second, while 43.7% ranked “route of administration” as first or second (figure 6) • laboratory monitoring was ranked least important by more than half (53.0%) of the patients figure 6. reason for treatment choice ranking 37.1 22.8 17.0 11.9 10.0 1.3 21.2 20.9 15.0 20.3 19.1 3.5 22.1 18.6 15.5 20.2 18.0 5.6 12.2 19.1 22.3 19.8 14.7 11.8 5.9 12.4 21.3 19.5 16.0 24.9 1.5 6.2 8.8 8.3 22.2 53.0 0 10 20 30 40 50 60 sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g rank 1 (p < 0.001) rank 2 (p = 0.005) rank 3 (p = 0.030) rank 4 (p = 0.233) rank 5 (p = 0.005) rank 6 (p < 0.001) p at ie n ts , % conclusions • this large, real-world study provided an account of how psoriasis impacts patients’ lives and treatment choices • patients with severe disease, black patients, and patients receiving injectable treatments were more likely to choose the new oral treatment compared with patients with mild disease, white patients, and patients receiving apremilast, respectively • willingness to start the new psoriasis treatment was common among all treatment groups • the new treatment was viewed as causing less anxiety compared with injectables across all treatment groups • extent of skin clearance and route of administration were reported as the top-ranked reasons for patients' psoriasis treatment choice • consideration of the treatment characteristics that drive the decision-making of patients with psoriasis is crucial for making effective treatment recommendations in clinical practice reference 1. feldman sr, et al. j health econ outcomes res. 2016;4:141-157. acknowledgments • this study was sponsored by bristol myers squibb • medical writing and editorial assistance was provided by tulika bhushan bahukhandi, rph, ms, of peloton advantage, llc, an open health company, and funded by bristol myers squibb disclosures • awa: has served as a research investigator, scientific advisor, and/or speaker for abbvie, almirall, arcutis biotherapeutics, aslan, beiersdorf, boehringer ingelheim/parexel, bristol myers squibb, dermavant, dermira, eli lilly, epi, incyte, leo, janssen, nimbus, novartis, ortho dermatologics, pfizer, sanofi genzyme, sun, regeneron, and ucb • ls, dd, sk, and vp: employees of and may own stock options in bristol myers squibb • nj, sr, sj, and dp: employees of open health, which received consulting fees from bristol myers squibb • dw and kb: employees of rti health solutions, which received consulting fees from bristol myers squibb scientific content on demand to request a copy of this poster: scan qr code via a barcode reader application qr codes are valid for 30 days after the congress presentation date. evaluating treatment choice among patients with moderate or severe psoriasis in the united states april w. armstrong,1 sayeli jayade,2 sanika rege,2 namita joshi,2 vardhaman patel,3 david davidson,3 samaneh kalirai,3 daniel wolin,4 kimberly boyle,4 dipen patel,2 lauren seigel3 1keck school of medicine, university of southern california, los angeles, ca; 2open health, bethesda, md; 3bristol myers squibb, princeton, nj; 4rti health solutions, research triangle park, nc presented at the 2022 fall clinical dermatology conference; october 20–23, 2022; las vegas, nv this poster may not be reproduced without written permission from the authors.email for april w. armstrong, md, mph: aprilarmstrong@post.harvard.edu synopsis • while several psoriasis treatments are available and in development, different treatment modalities are associated with varying effectiveness, risks, and economic burden, and these factors are likely to influence patients’ decisions related to their psoriasis treatment1 • this study explored the element of treatment decision-making driven by patient experiences — a cross-sectional, web-based survey captured the demographic and clinical characteristics, treatment attributes affecting therapeutic decisions, and perceptions of a new, hypothetical, once-daily oral psoriasis treatment (deucravacitinib) among patients with moderate to severe plaque psoriasis • understanding the factors that drive patients’ treatment preference is crucial for guiding clinical decision-making objectives primary • to identify factors associated with the choice of a new once-daily oral psoriasis treatment with efficacy superior to that of existing oral therapies in patients with moderate to severe psoriasis currently receiving apremilast, tumor necrosis factor inhibitors (tnfis), ustekinumab, topicals, or nonprescription treatments secondary • to rank the importance of treatment attributes to patients with moderate to severe psoriasis using apremilast, tnfis, ustekinumab, topicals, or nonprescription treatments • to elicit views on a new once-daily oral psoriasis treatment among patients with moderate to severe psoriasis using apremilast, tnfis, ustekinumab, topicals, or nonprescription treatments target product profile (deucravacitinib) • tablet formulation with once-daily dosing • clinical studies showed: — 53% of patients reported clear/mostly clear skin within 4 months — 83% of patients who reported a 75% reduction in psoriasis severity maintained this improvement at 1 year — non-serious adverse events, such as cold-like symptoms, headache, diarrhea, nausea, rash, and risk of herpes infection, led to few discontinuations • regular laboratory monitoring is not required, although pre-initiation testing may be needed • out-of-pocket costs may be similar to those of the alternative psoriasis treatments in consideration methods • a cross-sectional, web-based survey of the demographics and clinical characteristics of patients with psoriasis, their views on treatment characteristics that affect treatment-related decisions, and their perceptions of a new, hypothetical, once-daily oral psoriasis treatment • patients were assigned to predefined treatment groups: apremilast, a tnfi, ustekinumab, a topical therapy/phototherapy, and over-the-counter (otc) treatments or no treatment, based on their self-reported current treatment at the time of the survey • a hypothetical psoriasis treatment profile, described by dosage, efficacy, adverse effects, and out-of-pocket costs, was shown to the patients to elicit their views on: (1) interference with everyday life, (2) convenience, (3) treatment-related anxiety, and likelihood of initiating treatment, both (4) without a safety warning and (5) with a safety warning inclusion criteria • ≥18 years of age • residing in the united states • able to read and understand english • physician-diagnosed (self-reported) moderate or severe plaque psoriasis exclusion criteria • mild psoriasis • lack of online consent for the web-based survey data collection process • the study was reviewed and approved by an institutional review board • the study used a convenience sample of patients with moderate or severe psoriasis who were recruited by global perspectives to collect patient-reported data • patients were asked to complete an electronic patient survey that included questions from patient-reported outcome (pro) instruments and de novo questions • potential survey participants were provided with a link to the survey and completed screening questions to determine eligibility, followed by an informed consent checkbox • the final survey was administered to 882 patients statistical analysis • stepwise multivariable logistic regression was conducted to determine sociodemographic and clinical characteristics associated with the choice of the new treatment among patients who were currently receiving treatment or who had never received treatment — independent variables: treatment group, age, sex, race/ethnicity, psoriasis severity over the past week, comorbidities, disease and treatment duration, presence of psoriatic arthritis (psa) at baseline, number of flares, and number of body regions affected • treatment attributes (route of administration, extent of skin clearance, laboratory monitoring, durability, safety, and dosing frequency) were ranked as an ordinal category (scale of 1–6) by patients • chi-square test was conducted to detect significant differences between patient rankings of each treatment attribute and to assess the variations in patient views on the new oral treatment results • figure 1 shows the responses of the 5 baseline treatment groups surveyed • the study sample included 882 patients (mean age = 45.7 [±12.8] years); the majority were female (67.7%), most were white (74.9%), and their average duration of time since psoriasis diagnosis was 14.9 (±11.8) years (figures 2 and 3; table 1) • of 882 patients, 818 (92.8%) were currently receiving treatment and had been on their current treatment for a mean of 2.9 (±4.8) years (table 2) • with their current treatment regimen, 50.8% of patients in the total study population described their psoriasis over the past week as mild, very mild, or none, while 36.5% reported it as moderate and 12.7% reported it as severe or very severe (table 2) figure 1. targeted baseline treatment groups 344 242 98 98 100 0 50 100 150 200 250 300 350 400 p at ie n ts w h o c o m p le te d s u rv e y, n treatment group group 1: apremilast group 2: tnfi group 3: ustekinumab group 4: topical/phototherapy group 5: exploratorya athe exploratory group included patients who were using nonprescription treatments (n = 36), patients who had never received treatment (n = 17), and patients who had received treatment in the past but were not currently receiving treatment (n = 47). tnfi, tumor necrosis factor inhibitor. figure 2. key baseline characteristics, by sex (a) and race/ethnicitya (b) 74.9% 14.1% 2% 2% 0.2% 2.4% 6.1% white black american indian/ alaska native asian native hawaiian/ other pacific islander other preferred not to answer b.a. male female preferred not to answer 32.0% 67.7% 0.3% apercentages sum to >100% because respondents could select multiple races/ethnicities, as applicable. figure 3. key baseline characteristics for all respondents by insurance typea 13.6% 11.9% 54.5% 21.1% 2.2% 3.4% medicare medicaid employer-sponsored private insurance individually purchased private insurance uninsured military/veterans' coverage apercentages sum to >100% because respondents could select more than 1 insurance type, as applicable. table 1. key baseline characteristics for all respondents by patient age category all respondents (n = 882) mean 45.71 median (q1–q3) 45 range 18–76 q1–q3, quartiles 1–3. table 2. key baseline clinical characteristics parameter statistic or category all respondents, n = 882 (%) treatment status, n (%) currently receiving treatment 818 (92.8) was receiving treatment but has stopped 47 (5.3) never received treatment 17 (1.9) treatment duration, years mean (sd) 2.86 (4.81) median (q1–q3) 1.0 (0.0–3.0) range 0.0–42.0 current treatment type, n (%) over-the-counter nonprescription 225 (27.5) topical prescription steroid 230 (28.1) topical vitamin d analog 49 (6.0) other topical treatment 55 (6.7) ultraviolet light/phototherapy 51 (6.2) apremilast 356 (43.5) ustekinumab 101 (12.3) tnfi treatment 251 (30.7) psoriasis severity over the past week, n (%) none 31 (14.8) very mild 155 (17.6) mild 162 (18.4) moderate 322 (36.5) severe 86 (9.8) very severe 26 (2.9) bsa, body surface area; q1–q3, quartiles 1–3; sd, standard deviation; tnfi, tumor necrosis factor inhibitor. • among patients who were currently receiving treatment or who had never received treatment (n = 835), apremilast (41.2%) and tnfis (29.0%) were the most commonly used treatments, and otc or no treatment was the least common group (6.3%) (table 3) • of patients who had never received treatment, 88.2% expressed intent to start the new oral psoriasis treatment, compared with 80.6% of patients who used nonprescription otc treatment, 75.5% of patients who used ustekinumab, 74.0% of patients who used a tnfi, 69.4% of patients who used topical therapy, and 55.2% of patients who used apremilast (figure 4) • willingness to start the new, once-daily oral treatment was high across all groups, including patients currently using apremilast • in response to questions about the new treatment, 83.7% reported that it would be convenient, 65.0% reported that it would cause less anxiety than an injection or infusion, 55.3% reported that it would interfere less with their everyday life, and 50.2% reported that it would reduce their symptoms more than their current psoriasis treatment (figure 5) table 3. intent to start a new once-daily oral psoriasis treatment variable category intent to start new treatment all, n = 835 (%) yes, n = 555 (%) no, n = 280 (%) treatment group apremilast 344 (41.2) 190 (34.2) 154 (55.0) tnfi 242 (29.0) 179 (32.3) 63 (22.5) ustekinumab 98 (11.7) 74 (13.3) 24 (8.6) topical therapy 98 (11.7) 68 (12.3) 30 (10.7) otc or no treatment 53 (6.3) 44 (7.9) 9 (3.2) race/ethnicity white 610 (73.1) 390 (70.3) 220 (78.6) black 114 (13.7) 95 (17.1) 19 (6.8) asian, american indian/alaska native, native hawaiian/other pacifi c islander 32 (3.8) 21 (3.8) 11 (3.9) preferred not to answer 54 (6.5) 29 (5.2) 25 (8.9) other 25 (3.0) 20 (3.6) 5 (1.8) psoriasis severity over the past week (based on a 6-point scale) none 130 (15.6) 48 (8.6) 82 (29.3) mild 308 (36.9) 197 (35.5) 111 (39.6) moderate 298 (35.7) 228 (41.1) 70 (25.0) severe 99 (11.9) 82 (14.8) 17 (6.1) otc, over the counter; tnfi, tumor necrosis factor inhibitor. figure 4. intent to start a new once-daily oral treatment, by treatment group (a), race/ ethnicity (b), and psoriasis severity over the past week (c), all p < 0.001 55.2% 74.0% 75.5% 69.4% 83.0% 0 10 20 30 40 50 60 70 80 90 100 ap re m ila st tn fi us te ki nu m ab to pi ca l t he ra py w hi te bl ac k pr ef er re d no t to a ns we r ot he r no ne mi ld mo de ra te se ve re ot c or n o tr ea tm en t as ia n, a m er ic an in di an / al as ka n at iv e, n at iv e ha wa iia n/ ot he r p ac ifi c isl an de r p at ie n ts , % 63.9% 83.3% 65.6% 53.7% 80.0% a. b. 36.9% 64.0% 76.5% 82.8% c. 0 10 20 30 40 50 60 70 80 90 100 p at ie n ts , % 0 10 20 30 40 50 60 70 80 90 100 p at ie n ts , % otc, over the counter; tnfi, tumor necrosis factor inhibitor. figure 5. views on a new once-daily oral treatment, by treatment group 0 10 20 30 40 50 60 70 80 90 100 p at ie n ts , % yes neither yes nor no no yes neither yes nor no no yes neither yes nor no no yes neither yes nor no no yes no less interference with daily life (p < 0.001) convenience of treatment (p = 0.094) less anxiety than with injection/infusion (p = 0.041) reduction in symptoms compared with current treatment (p < 0.001) intent to start new oral psoriasis treatment (p < 0.001) apremilast (n = 344) tnfi (n = 242) ustekinumab (n = 98) topical therapy/phototherapy (n = 98) tnfi, tumor necrosis factor inhibitor. • only treatment group, race/ethnicity, and psoriasis severity were statistically significant factors in the model • the following responses were examined for intent to start a new once-daily oral treatment (yes/no), by selected categories: — 83% of black respondents would start the new once-daily oral treatment • compared with white patients, the odds ratio (or) of intent to start the new treatment was 2.4 (95% confidence interval [ci], 1.4–4.2) among black respondents (p = 0.036) — intent to start the new once-daily oral treatment increased with psoriasis severity over the past week, with 76.5% of respondents with moderate psoriasis and 82.8% of respondents with severe disease answering “yes” • compared with patients with no psoriasis symptoms or signs over the past week, the or of intent to start the new treatment was 3.2 (95% ci, 2.0–4.9) among patients with mild psoriasis, 5.0 (95% ci, 3.1–8.2) among patients with moderate psoriasis, and 7.6 (95% ci, 3.9–15.0) among patients with severe psoriasis; all p < 0.001 — 79.6% of patients who responded that the new once-daily oral treatment would cause them less anxiety than an injection would start the new treatment — 87.6% of respondents who believed that the new once-daily oral treatment would reduce their symptoms more than their current treatment would start the new treatment • asked to rank characteristics of psoriasis treatment in order of importance, 58.3% of respondents ranked “extent of skin clearance” as first or second, while 43.7% ranked “route of administration” as first or second (figure 6) • laboratory monitoring was ranked least important by more than half (53.0%) of the patients figure 6. reason for treatment choice ranking 37.1 22.8 17.0 11.9 10.0 1.3 21.2 20.9 15.0 20.3 19.1 3.5 22.1 18.6 15.5 20.2 18.0 5.6 12.2 19.1 22.3 19.8 14.7 11.8 5.9 12.4 21.3 19.5 16.0 24.9 1.5 6.2 8.8 8.3 22.2 53.0 0 10 20 30 40 50 60 sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g sk in c le ar an ce r ou te o f ad m in is tr at io n sa fe ty d os in g fr e q u e n cy d u ra b il it y of r e sp on se la b or at or y m on it or in g rank 1 (p < 0.001) rank 2 (p = 0.005) rank 3 (p = 0.030) rank 4 (p = 0.233) rank 5 (p = 0.005) rank 6 (p < 0.001) p at ie n ts , % conclusions • this large, real-world study provided an account of how psoriasis impacts patients’ lives and treatment choices • patients with severe disease, black patients, and patients receiving injectable treatments were more likely to choose the new oral treatment compared with patients with mild disease, white patients, and patients receiving apremilast, respectively • willingness to start the new psoriasis treatment was common among all treatment groups • the new treatment was viewed as causing less anxiety compared with injectables across all treatment groups • extent of skin clearance and route of administration were reported as the top-ranked reasons for patients' psoriasis treatment choice • consideration of the treatment characteristics that drive the decision-making of patients with psoriasis is crucial for making effective treatment recommendations in clinical practice reference 1. feldman sr, et al. j health econ outcomes res. 2016;4:141-157. acknowledgments • this study was sponsored by bristol myers squibb • medical writing and editorial assistance was provided by tulika bhushan bahukhandi, rph, ms, of peloton advantage, llc, an open health company, and funded by bristol myers squibb disclosures • awa: has served as a research investigator, scientific advisor, and/or speaker for abbvie, almirall, arcutis biotherapeutics, aslan, beiersdorf, boehringer ingelheim/parexel, bristol myers squibb, dermavant, dermira, eli lilly, epi, incyte, leo, janssen, nimbus, novartis, ortho dermatologics, pfizer, sanofi genzyme, sun, regeneron, and ucb • ls, dd, sk, and vp: employees of and may own stock options in bristol myers squibb • nj, sr, sj, and dp: employees of open health, which received consulting fees from bristol myers squibb • dw and kb: employees of rti health solutions, which received consulting fees from bristol myers squibb scientific content on demand to request a copy of this poster: scan qr code via a barcode reader application qr codes are valid for 30 days after the congress presentation date. skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 714 brief article characterizing skin cancers arising for the first time following solid organ transplant with subsequent recurrence chelsea shope, mscr1, laura andrews, mscr1, courtney linkous, ba1, ashley girvin, bs1, hannah neimy, bs1, lara wine lee, md, phd2 1 college of medicine, medical university of south carolina, charleston, sc 2 department of dermatology & dermatologic surgery, medical university of south carolina, charleston, sc there is an established relationship between solid organ transplantation (sot) and increased incidence of skin cancers.1 exposure to ultraviolet a (uva, 280 – 315 nm) and ultraviolet b (uvb, 315 – 400 nm) radiation significantly increases risk of developing keratinocyte carcinoma (kc) and malignant melanoma (mm) by promoting dna damage and stimulating inflammation.2 in patients receiving immunosuppressive treatment necessary to prevent graft rejection following any transplant, natural immunosurveillance mechanisms are inhibited.2 thus, there is an observed association between chronic immunosuppression and increased carcinogenesis as well as persistence of oncogenic viral infections.3 in patients diagnosed with either kc or mm prior to organ transplantation, there have been observed increases in both mortality and recurrence,4 however, little is known regarding skin cancers which arise for the abstract introduction: there is an established relationship between solid organ transplantation (sot) and increased incidence of skin cancers. there is a paucity of data characterizing skin cancers arising for the first-time post-transplant that subsequently recur. methods: we conducted a retrospective review to identify sot recipients (sotrs) at our institution with recurrence of skin cancer that initially developed post-transplant (“recurrence”). patients with pre-transplant history of skin cancer were excluded. data was analyzed using one-sample t-tests. results: of 530 sotrs identified, 33 had recurrence (mean 3.97 + 6.97). sotrs with recurrence were male (87.9%), white (97%), renal recipients (75.7%) with a mean age at transplant of 56.52 [+11.69] years (p-value<0.001 each). recurrences arose from scc (66.7%) on the face or scalp (57.5%), which were invasive at time of diagnosis (63.6%) (pvalue<0.001 each). conclusion: in our cohort, white renal and cardiac transplants and a history of smoking appear to have a higher risk for recurrence of de novo post-transplant skin cancers. our data supports that all sotrs should have close and routine dermatologic follow-up due to risk for skin malignancy, which are disproportionately high-risk and invasive at the time of presentation. introduction skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 715 first-time post-transplant and subsequently recur. we aimed to further characterize the incidence of such recurrences in sot recipients (sotrs). after irb approval was received by the medical university of south carolina (irb-i, pro00120456), a retrospective review was conducted to identify sotrs at our institution who were seen within a dermatology clinic. patients who had a history of skin cancer prior to transplant were excluded. demographic data and information regarding transplant and dermatologic course were collected. patients were then stratified by presence of any skin cancer arising for the first-time post-transplant, and then further divided by subsequent recurrence of posttransplant skin cancers (hereafter referred to as recurrence). data was analyzed using one-sample t-tests. between january 1, 2012, and june 1, 2022, 530 sotrs were seen within a dermatology clinic. the majority were white (63.58%) and male (70.19%), with a mean age of 49.44 years at time of transplant. among sotrs, 203 patients (38.3%) developed 1,641 skin cancers for the first-time following transplant, which included kc, mm, merkel cell carcinoma (mcc), and porocarcinoma. sotrs with cancerous lesions were white (95.1%), male (72.9%), renal transplant recipients (64.0%) with a mean age of 54.33 [+11.52] years at transplant. a total of 33 patients experienced at least 1 recurrence arising from a de novo posttransplant skin cancer (mean 3.97 + 6.97). patients with recurrence were most often male (87.9%, p-value<0.001), white (97%, pvalue<0.001), renal transplant recipients (75.7%, p-value<0.001) with a mean age at transplant of 56.52 [+11.69] years. slightly over half of patients are currently living (57.6%). patients were also likely to be current or former smokers (57.6%, (pvalue<0.001) (table 1). significant comorbid conditions include hypertension (p-value<0.001), type 2 diabetes (p-value=0.002), hyperlipidemia (pvalue<0.001), chronic kidney disease/end stage renal disease (p-value<0.001), and cardiomyopathy or coronary artery disease (p-value<0.001) (table 1). risk factors for recurrence include family history of skin cancer (p-value=0.006), heart transplant (pvalue=0.006), and the use of post-transplant meds including tacrolimus (p-value<0.001), cyclosporine (p-value=0.006), mycophenolate mofetil (mmf) (pvalue<0.001), and prednisone ((pvalue<0.001) (table 2). first skin cancers were most commonly scc (66.7%, p-value<0.001), and invasive at time of diagnosis (63.6%, p-value<0.001), of which half were high risk (50%, pvalue=0.006). subsequent skin cancers were most often scc (69.7%, p-value<0.001). skin cancers most frequently developed on the face or scalp (57.5%, p-value<0.001) (table 2). given improvements made in post-transplant mortality rates with standardized immunosuppressive therapies, patients are living longer and incidence of post-transplant morbidities such as cutaneous malignancies are increased.1 skin cancers account for approximately 40% of all post-transplant malignancies. in fact, it is estimated that as methods results discussion skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 716 table 1. patient demographics of organ transplant recipients with first skin cancer occurring post-transplant, with subsequent recurrence. all sotrs (n=530) sotrs with posttransplant skin cancer (n=203) sotrs with recurrent posttransplant skin cancer (n=33) p-value age at transplant (mean, sd) 49.44 [+16] 54.33 [+11.52] 56.52 [+11.69] <0.001* race (n, %) <0.001* african american 177 (33.4%) 7 (3.4%) 0 (0%) american indian/alaska native 2 (0.4%) 1 (0.5%) 0 (0%) asian 7 (1.3%) 0 (0%) 0 (0%) caucasian 337 (63.6%) 193 (95.1%) 32 (97%) hispanic or latino 5 (0.9%) 1 (0.5%) 1 (3.0%) pacific islander 1 (0.2%) 0 (0%) 0 (0%) other 1 (0.2%) 1 (0.5%) 0 (0%) sex (n, %) <0.001* female 372 (70.2%) 148 (72.9%) 4 (12.1%) male 203 (29.8%) 55 (27.1%) 29 (87.9%) transplant type (n, %)+ <0.001* renal 374 (70.6%) 130 (64.0%) 25 (75.7%) liver 80 (15.1%) 37 (18.2%) 1 (3.0%) heart 85 (16.0%) 45 (22.2%) 7 (21.2%) lung 16 (3.0%) 10 (4.9%) 2 (6.1%) pancreas 49 (9.2%) 21 (10.3%) 1 (3.0%) smoking status <0.001* never smoker 270 (50.9%) 78 (38.4%) 14 (42.4%) current smoker 18 (3.4%) 7 (3.4%) 1 (3.0%) former smoker 242 (45.7%) 118 (58.1%) 18 (54.5%) comorbid conditions hypertension 397 (74.9%) 146 (71.9%) 23 (69.7%) <0.001* type 2 diabetes mellitus 187 (35.3%) 59 (29.1%) 9 (27.3%) 0.002 hyperlipidemia 198 (37.4%) 86 (42.4%) 14 (42.4%) <0.001* ckd/esrd 289 (54.5%) 100 (49.3%) 21 (63.6%) <0.001* cardiomyopathy/cad 143 (27.0%) 55 (27.1%) 10 (30.3%) <0.001* sotr: solid organ transplant recipient ckd: chronic kidney disease esrd: end-stage renal disease *indicates statistically significant result (p-value <0.05) +patients may have received more than one organ type skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 717 table 2. risk factors for skin cancer recurrence in organ transplant recipients with skin cancer arising for the first-time post-transplant. sotrs with recurrent skin cancer (n = 33) p-value family history of skin cancer 0.006* post-transplant medications (n, %) tacrolimus 25 (75.8%) <0.001* cyclosporine 7 (21.2%) 0.006* mycophenolate mofetil 18 (54.5%) <0.001* prednisone 27 (81.8%) <0.001* type of first skin cancer (n, %) squamous cell carcinoma 22 (66.7%) <0.001* sccis* 7 (31.8%) 0.006* invasive+ 14 (63.6%) <0.001* low risk 4 (28.6%) high risk 7 (50.0%) very high risk 4 (28.6%) basal cell carcinoma 11 (33.3%) <0.001* melanoma in situ 1 (3.0%) 0.325 location of skin cancer (n, %) <0.001* scalp 8 (24.2%) face 12 (36.4%) neck 2 (6.1%) chest or back 3 (9.1%) upper extremities 5 (15.2%) lower extremities 2 (6.1%) unknown 1 (3.0%) total number of skin cancers (n) n = 412 squamous cell carcinoma 269 (65.3%) basal cell carcinoma 138 (33.5%) malignant melanoma 5 (1.2%) *sccis: squamous cell carcinoma in situ. **indicates statistically significant result (p-value <0.05) +low risk: trunk/extremities, <2 cm or well/moderately differentiated, <6 mm deep. high risk: trunk/extremities, 2 -4 cm or anywhere on head/neck. very high risk: any site >4 cm or poorly differentiated, >6 mm deep, or perineural/lymphatic involvement. skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 718 many as 70% of patients with lower fitzpatrick phototypes (i or ii) will be diagnosed with a skin cancer within 20 years following transplant.5 among our cohort, there was a correlation between white patients, who tend to have fitzpatrick phototypes i or ii, and a higher risk for recurrence of skin cancers that arose for the first time post-transplant, in the absence of a pre-transplant history of skin cancer. other risks factors correlated with recurrence among our cohort included renal or cardiac transplant, smoking status, and family history of skin cancer. common transplant medications such as tacrolimus, cyclosporine, mmf, and prednisone were also correlated with increased risk for skin cancer recurrence. it is evident that regular practice of skin cancer prevention strategies is critical for immunosuppressed patients.1 transplant recipients should perform monthly cutaneous self-examinations. as sotrs are high-risk for post-transplant skin cancer, which are disproportionately high-risk and invasive at the time of diagnosis, transplant recipients should have regular and close examinations performed by a dermatologist. additionally, a potential modification of the immunosuppressive treatment regimen should be considered should skin cancer arise.4 conflict of interest disclosures: none funding: none corresponding author: chelsea shope, mscr 135 rutledge ave, 11th floor charleston, sc 29425 email: shopec@musc.edu references: 1. collins l, quinn a, stasko t. skin cancer and immunosuppression. dermatol clin. 2019;37(1):83-94. 2. moyal dd, fourtanier am. broad-spectrum sunscreens provide better protection from solar ultraviolet-simulated radiation and natural sunlight-induced immunosuppression in human beings. j am acad dermatol. 2008;58(5 suppl 2):s149-154. 3. nindl i, rösl f. molecular concepts of virus infections causing skin cancer in organ transplant recipients. am j transplant. 2008;8(11):2199-2204. 4. o'reilly zwald f, brown m. skin cancer in solid organ transplant recipients: advances in therapy and management: part i. epidemiology of skin cancer in solid organ transplant recipients. j am acad dermatol. 2011;65(2):253-261. 5. baldwin s, au s. one-year review of the screen (skin cancer post-transplant) clinic. j cutan med surg. 2017;21(1):80-81. conclusion skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 559 brief articles merkel cell carcinoma presenting as an indurated plaque margaret maxi, md1, joel byrne, bs1, ardenne martin, bs1, pam martin, md1 1louisiana state university health sciences center (lsuhsc) school of medicine, new orleans, la merkel cell carcinoma (mcc) is a rare and aggressive neuroendocrine carcinoma that most commonly occurs in elderly caucasian men who have a history of extensive sun exposure. the incidence of mcc increased threefold from 1986 to 2001 and is predicted to continue to increase since the “baby boomer” population is aging, and the risk of mcc increases with age.1,2 most cases of mcc present in the outpatient setting and include a single, asymptomatic, red to pink lesion on sun exposed areas (most commonly in the head and neck region) with a diameter less than 2 cm.3 however, diagnosis is often challenging due to a combination of low suspicion by clinicians and a range of possible clinical presentations. we report an unusual presentation of mcc in form of an indurated plaque with metastasis. a 93-year-old caucasian man with a history of vitamin d deficiency, actinic keratoses, and basal cell carcinoma of the head and neck presented to the hospital with a 2month history of progressive swelling, oozing, and redness of his right chest wall and right arm. he denied any associated chest pain. dermatology was consulted for chest wall rash that was initially diagnosed as cellulitis by the primary team. physical examination revealed an elderly cachectic male with an ill-defined erythematous, indurated, and edematous plaque involving most of right chest wall and extending to the right upper arm (figure 1). the periareolar skin had a peau d’orange appearance with a wound draining serosanguinous fluid. right axillary, right supraclavicular, and left axillary lymphadenopathy was present. abstract merkel cell carcinoma (mcc) is a rare and aggressive neuroendocrine carcinoma that most commonly occurs in elderly caucasian males who have a history of extensive sun exposure. most cases of merkel cell carcinoma (mcc) present in the outpatient setting and include a single, asymptomatic, red or pink lesion on sun exposed areas with a diameter less than 2 cm. there was a threefold increase in the incidence of mcc from 1986 to 2001, and the incidence of mcc is predicted to continue to increase secondary to the aging “baby boomer” population. to our knowledge, there are only two case reports that describe mcc resembling and receiving the diagnosis of cellulitis at initial presentation. we report an unusual case of mcc presenting as suspected cellulitis of the chest wall in an elderly caucasian male. introduction case presentation skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 560 figure 1. initial clinical presentation of mcc on right chest wall. a chest ct scan demonstrated a right sided pleural effusion, diffuse anasarca, bilateral lung opacities, diffuse adenopathy, diffuse skin thickening, and nodular infiltration of the right chest with possible involvement of the musculature. biopsy of the chest wall exhibited a diffuse dermal infiltrate of polygonal cells with variably sized nuclei and finely granular “blastic” chromatin with occasional macronucleoli (figures 2 and 3). the tumor cells showed paranuclear punctate positivity for ck20, ck8, panck, synaptophysin, and neurofilament, while s100 and ttf-1 were negative. the diagnosis of mcc was made. following discussion with his family, the patient decided to forgo treatment due to his age and extent of disease, choosing quality of life over quantity. he was discharged to hospice care and subsequently died. despite its increasing incidence, mcc is rarely suspected by clinicians prior to biopsy. in a review of initial clinical impressions of 106 mcc cases, the correct figure 2. histopathology of biopsy from right chest wall demonstrates dermal infiltrate of mcc. figure 3. closer inspection of biopsy reveals polygonal cells with variably sized nuclei consistent with mcc. clinical diagnosis of mcc was made in only 1% of patients, with 56% of cases receiving benign clinical impressions initially.3 heath et al. created an acronym to guide clinicians in identifying common characteristics: aeiou asymptomatic/lack of tenderness (88%), expanding rapidly within 3 months (63%), immune suppression (7.8%), older than age 50 (90%), uv-exposed site (81%). in a discussion skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 561 cohort study of 195 patients diagnosed with mcc from 1980 to 2007, 89% of patients met 3 or more of the aeiou criteria.3 our patient met 3 of the criteria, as he had an asymptomatic/nontender lesion that expanded rapidly within 3 months and was older than age 50. however, the clinical appearance of our patient’s tumor was atypical as the lesion was a large plaque as opposed to the typical 1-2 cm solitary lesion. moreover, our patient was not immunocompromised, and the location of our patient’s lesion was particularly rare, as heath et al. observed trunk lesions at initial presentation in only 8% of patients. while the use of aeiou criteria is beneficial in terms of bringing awareness to typical mcc clinical phenotypes, it is important to know that clinical characteristics of mcc vary greatly and are nonspecific. there are recorded cases of mcc presenting with the clinical appearance of chalazion and cellulitis.4,5 other cases have had unusual morphologies like ulcerated and pedunculated masses.4,6 atypical age and location are also possible with reports of mcc occurring in young adults and teenagers and in the gluteal region and oral cavity.4,7 as a result of the diverse and nonspecific clinical characteristics of mcc, definitive diagnosis is based on histopathologic means, with cam 5.2, ck20 (characteristically paranuclear and dot-like), and neurofilaments being specific for mcc.8,9 mcc is an aggressive tumor with a propensity for nodal and distant metastasis, high rates of recurrence, and mortality rates that are higher than melanoma.10 in an analysis of over 9,000 mcc cases from 1998-2012, lymph node involvement at initial presentation of mcc was documented in 26% of cases, with metastatic disease occurring in 8% of cases.11 extent of disease at presentation serves as a predictor of mortality, as local, nodal, and metastatic disease at presentation correlate to 51%, 35%, and 14% 5-year survival rates.11 patients who present with distant metastasis have a median survival time of 9 months, which is longer than the time our patient survived following his diagnosis.12 the progressively poorer prognoses associated with more advanced cases of mcc emphasize the importance of early identification of at-risk patients with skin lesions suspicious for mcc. management of mcc varies based on disease stage and patient characteristics. a multidisciplinary approach in assessment and treatment is recommended as definitive therapeutic guidelines are not clearly established. evaluation of regional and distant metastasis is required, with the dichotomy of clinically positive versus clinically negative lymph nodes serving as the first step in assessment.13 wide local excision of the primary lesion is typically recommended as the first step in treatment followed by adjuvant radiation therapy.13 in metastatic cases, immunotherapy is now the preferred treatment modality as there appears to be an improved durability of response with immunotherapy compared to chemotherapy.14 clinical trials are currently evaluating avelumab, an anti-programmed death ligand 1 (pd-l1) agent, and pembrolizumab and nivolumab, antiprogrammed cell death-1 (pd-1) receptor agents, with promising results.15,16,17 our case covers an interesting and significant dermatologic topic as it describes a unique presentation of a rare tumor with a poor prognosis that is increasing in incidence and has emerging treatments. conclusion skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 562 conflict of interest disclosures: none funding: none corresponding author: margaret maxi, md 424 11h st neenah wi, 54956 phone: 502-314-4321 email: maggie.coleman@gmail.com references: 1. paulson kg, park sy, vandeven na, lachance k, thomas h, chapuis ag, harms kl, thompson ja, bhatia s, stang a, nghiem p. merkel cell carcinoma: current us incidence and projected increases based on changing demographics. journal of the american academy of dermatology. 2018;78(3):457463.e2. 2. hodgson nc. merkel cell carcinoma: changing incidence trends. journal of surgical oncology 2005;89:1-4. 3. heath m, jaimes n, lemos b, mostaghimi a, wang lc, peñas pf, nghiem p. clinical characteristics of merkel cell carcinoma at diagnosis in 195 patients: the aeiou features. journal of the american academy of dermatology. 2008 mar;58(3):375-81. 4. enzo errichetti, angelo piccirillo, federico ricciuti, and francesco ricciuti. pedunculated and telangiectatic merkel cell carcinoma: an unusual clinical presentation. indian journal of dermatology. 2013 may-jun; 58(3): 243. 5. safa f, pant m, weerasinghe c, felix r, terjanian t. merkel cell carcinoma masquerading as cellulitis: a case report and review of the literature. current oncology. 2018 feb;25(1):e106-e112. 6. regueiro rf, sánchez fjs, morís-dela-tassa j. merkel cell carcinoma. report of a case with an atypical location and presentation. revista española de cirugía ortopédica y traumatología. revista española de cirugía ortopédica y traumatología. jul-aug 2019;63(4):313-315. 7. islam mn, chehal h, smith mh, islam s, bhattacharyya i. merkel cell carcinoma of the buccal mucosa and lower lip. head and neck pathology. 2018 jun; 12(2): 279–285. 8. coggshall k, tello tl, north jp, yu ss. merkel cell carcinoma: an update and review: pathogenesis, diagnosis, and staging. journal of the american academy of dermatology. 2018 mar;78(3):433-442. 9. doval jv, cussac bl, bustillo ap, morena sp, gonzález mjf, figueras mtf, villanueva mj, salas nr, descalzo-gallego ma, garcía-doval i, ríosbucetak l. diagnosis and treatment of merkel cell carcinoma in specialized dermatology units: a clinical practice guideline of the spanish academy of dermatology and venereology. actas dermosifiliográficas. 2019 jul-aug;110(6):460-468. 10. grabowski j, saltzstein sl, sadler gr, tahir z, blair s. a comparison of merkel cell carcinoma and melanoma: results from the california cancer registry. clinical medicine: oncology. 2008 apr 1;2:327–333. 11. harms kl, healy ma, nghiem p, sober aj, johnson tm, bichakjian ck, and wong sl. analysis of prognostic factors from 9387 merkel cell carcinoma cases forms the basis for the new 8th edition ajcc staging system. annals of surgical oncology. 2016 oct;23(11):3564–3571. 12. allen pj, bowne wb, jaques dp, brennan mf, busam k, coit dg. merkel cell carcinoma: prognosis and treatment of patients from a single institution. journal of clinical oncology. 2005 apr 1;23(10):2300-2309. 13. villani a, fabbrocini g, costa c, annunziata mc, and scalvenzi m. merkel cell carcinoma: therapeutic update and emerging therapies. dermatology and therapy. 2019 jun;9(2):209–222. 14. isaac s. chan is, bhatia s, kaufman hl, lipson ej. immunotherapy for merkel cell carcinoma: a turning point in patient care. journal for immunotherapy of cancer. 2018;6:23. 15. kaufman hl, russell js, hamid o, bhatia s, terheyden p, d'angelo sp, shih kc, lebbé c, milella m, brownell i, lewis kd, lorch jh, heydebreck a, hennessy m, nghiem p. updated efficacy of avelumab in patients with previously treated metastatic merkel cell carcinoma after ≥1 year of follow-up: javelin merkel 200, a phase 2 clinical trial. journal for immunotherapy of cancer. 2018 jan 19;6(1):7. 16. nghiem p, bhatia s, lipson ej, sharfman wh, kudchadkar rr, brohl as, friedlander pa, daud a, kluger hm, reddy sa, boulmay bc, riker ai, burgess ma, hanks ba, olencki t, margolin k, lundgren lm , soni a, ramchurren n, church c, park sy, shinohara mm, salim b, taube jm, bird sr, ibrahim n, fling sp, moreno bh, sharon e, cheever ma, topalian sl. durable tumor regression and overall survival in patients with advanced merkel cell carcinoma receiving pembrolizumab as first-line therapy. journal for immunotherapy of cancer. 2019 mar 20;37(9):693702. 17. walocko fm, scheier by, harms pw, fecher la, lao cd. metastatic merkel cell carcinoma response to nivolumab. journal for immunotherapy of cancer. 2016 nov 15;4:79. acknowledgements: medical writing support was provided by prescott medical communications group (chicago, il) with financial support from ortho dermatologics; ortho dermatologics is a division of bausch health us, llc | presented at winter clinical dermatology conference 2020 • january 17-22, 2020 • kohala coast, hi synopsis ◾ acne is the most common dermatologic issue in patients with skin of color1 ◾ additionally, the prevalence of acne in adults is increasing, and it occurs more often in adult females than males2,3 ◾ the first lotion formulation of tretinoin 0.05%, developed by utilizing novel polymeric emulsion technology, was efficacious and well tolerated in two phase 3 studies of patients ≥9 years of age with moderate-to-severe acne (nct02932306, nct02965456)4 objective ◾ to assess efficacy of this novel tretinoin 0.05% lotion in participants by gender as well as black and white race (self-identified) methods ◾ in two phase 3, randomized, multicenter, double-blind, parallel-group, vehicle-controlled studies, participants with moderate-to-severe acne were equally randomized to tretinoin 0.05% lotion or vehicle lotion once daily for 12 weeks • in these studies, cerave® hydrating cleanser and cerave® moisturizing lotion (l’oreal, ny) were provided as needed for optimal moisturization/ cleaning of the skin ◾ a pooled post hoc analysis was conducted to evaluate the effect of gender and race on the efficacy of tretinoin 0.05% lotion ◾ efficacy assessments included change from baseline in inflammatory/noninflammatory lesion counts and percentage of participants achieving treatment success, defined as ≥2-grade reduction in the evaluator global severity score (egss) and a clear/ almost clear score efficacy of a novel tretinoin 0.05% lotion in the treatment of moderate-to-severe acne by gender and race: pooled analysis of two phase 3 studies figure 1. mean percent reduction from baseline in inflammatory (a) and noninflammatory (b) lesion counts by gender and visit (itt population, pooled) -30.2% -46.1% -56.9% -27.1% -38.7% -47.1% -70% -60% -50% -40% -30% -20% -10% ls m e a n p e rc e n t c h a n g e f ro m b a se lin e females tretinoin 0.05% lotion (n=433) vehicle lotion (n=476) baseline week 4 week 8 week 12 a. in�ammatory lesions b. nonin�ammatory lesions -26.0% -39.2% -53.4% -21.8% -30.2% -39.4% -70% -60% -50% -40% -30% -20% -10% 0% ls m e a n p e rc e n t c h a n g e f ro m b a se lin e males baseline week 4 week 8 week 12 tretinoin 0.05% lotion (n=386) vehicle lotion (n=345) -24.1% -38.2% -51.7% -17.1% -27.5% -34.9% -70% -60% -50% -40% -30% -20% -10% 0% ls m e a n p e rc e n t c h a n g e f ro m b a se lin e females tretinoin 0.05% lotion (n=433) vehicle lotion (n=476) baseline week 4 week 8 week 12 -22.9% -34.9% -46.1% -15.6% -22.7% -29.7% -70% -60% -50% -40% -30% -20% -10% 0% ls m e a n p e rc e n t c h a n g e f ro m b a se lin e males baseline week 4 week 8 week 12 tretinoin 0.05% lotion (n=386) vehicle lotion (n=345) 0% **p<0.01 vs vehicle; ***p≤0.001 vs vehicle. multiple imputation method used for missing values. itt, intent-to-treat; ls, least squares. figure 2. percentage of participants achieving treatment successa at week 12 by gender and race (itt population, pooled) 23.6% 13.5% 35% all p e rc e n ta g e o f p a rt ic ip a n ts 433 476 tretinoin 0.05% lotion vehicle lotion tretinoin 0.05% lotion vehicle lotion 30% 25% 20% 15% 10% 5% 0% 23.3% 12.6% white 286 336 23.0% 15.1% black 111 98 females 16.1% 7.6% 35% all p e rc e n ta g e o f p a rt ic ip a n ts 386 345 30% 25% 20% 15% 10% 5% 0% 15.4% 7.7% white 307 283 18.0% 10.2% black 54 45 males n= n= **p<0.01 vs vehicle; ***p≤0.001 vs vehicle. adefined as ≥2-grade reduction from baseline in evaluator’s global severity score with a final grade of 0 (clear) or 1 (almost clear). multiple imputation method used for missing values. itt, intent-to-treat. results participants ◾ a total of 1,640 participants were included in the pooled analysis • females (tretinoin, n=433; vehicle, n=476): white females (tretinoin, n=286; vehicle, n=336); black females (tretinoin, n=111; vehicle, n=98) • males (tretinoin, n=386; vehicle, n=345): white males (tretinoin, n=307; vehicle, n=283); black males (tretinoin, n=54; vehicle, n=45) ◾ mean age was slightly higher for females than males (mean age [standard deviation]): • females (22.4 years [8.2]): white females (22.0 [7.9]); black females (23.6 [8.7]) • males (18.1 years [5.2]): white males (18.0 [4.9]); black males (18.8 [6.4]) efficacy females and males: overall ◾ at week 12, all tretinoin-treated females and males had significantly greater mean percent reduction from baseline versus vehicle in inflammatory (figure 1a) and noninflammatory lesion counts (figure 1b) and a larger percentage achieved treatment success versus vehicle (figure 2) ◾ compared with males, tretinoin-treated females had greater mean percent reductions in noninflammatory lesion counts at week 12 (51.7% vs 46.1%; p<0.05) and a larger percentage achieved treatment success (23.6% vs 16.1%; p<0.05) females and males: by race ◾ at week 12, there were significant reductions in inflammatory and noninflammatory lesion counts with tretinoin treatment versus vehicle in white females, white males, and black males (figures 3a and 3b) ◾ compared with vehicle, significantly more tretinoin-treated white females and males achieved treatment success at week 12 (figure 2) ◾ the percentages of tretinoin-treated black males and females achieving treatment success were greater than vehicle, but these differences were not significant (figure 2) edward lain, md, mba1; doris day, md2; julie c harper, md3; eric guenin, pharmd, phd, mph4 1austin institute for clinical research, austin, tx; 2day dermatology and aesthetics, new york, ny; 3dermatology and skin care center of birmingham, birmingham, al; 4ortho dermatologics*, bridgewater, nj *ortho dermatologics is a division of bausch health us, llc. figure 3. mean percent reduction from baseline in inflammatory (a) and noninflammatory (b) lesion counts by gender, race, and visit (itt population, pooled) -70% -60% -50% -40% -30% -20% -10% 0% ls m e a n p e rc e n t c h a n g e f ro m b a se lin e females tretinoin: black females (n=111) vehicle: black females (n=98) baseline week 4 week 8 week 12 a. in�ammatory lesions b. nonin�ammatory lesions tretinoin: white females (n=286) vehicle: white females (n=336) -70% -60% -50% -40% -30% -20% -10% 0% ls m e a n p e rc e n t c h a n g e f ro m b a se lin e females tretinoin: black females (n=111) vehicle: black females (n=98) baseline week 4 week 8 week 12 tretinoin: white females (n=286) vehicle: white females (n=336) -70% -60% -50% -40% -30% -20% -10% 0% ls m e a n p e rc e n t c h a n g e f ro m b a se lin e males tretinoin: black males (n=54) vehicle: black males (n=45) baseline week 4 week 8 week 12 tretinoin: white males (n=307) vehicle: white males (n=283) -70% -60% -50% -40% -30% -20% -10% 0% ls m e a n p e rc e n t c h a n g e f ro m b a se lin e males tretinoin: black males (n=54) vehicle: black males (n=45) baseline week 4 week 8 week 12 tretinoin: white males (n=307) vehicle: white males (n=283) # ## ## ## white participants: *p<0.05 vs vehicle; **p<0.01 vs vehicle; ***p≤0.001 vs vehicle. black participants: #p<0.05 vs vehicle; ##p<0.01 vs vehicle. multiple imputation method used for missing values. itt, intent-to-treat; ls, least squares. conclusions ◾ tretinoin 0.05% lotion was significantly more effective than vehicle in reducing inflammatory and noninflammatory acne lesions and producing treatment success in males and females with moderate-to-severe acne ◾ tretinoin 0.05% lotion was also significantly more effective than vehicle in reducing inflammatory and noninflammatory acne lesions in white males and females and black males ◾ in black females, there were improvements in lesion count reductions and a greater percentage achieved treatment success with tretinoin 0.05% lotion, but no efficacy endpoints reached statistical significance versus vehicle; this may be due in part to the small sample size and/or the greater response to vehicle references 1. alexis af. j drugs dermatol. 2014;13(6):s61-65. 2. skroza n, et al. j clin aesthet dermatol. 2018;11(1):21-25. 3. collier cn, et al. j am acad dermatol. 2008;58(1):56-59. 4. tyring sk, et al. j drugs dermatol. 2018;17(10):1084-1091. author disclosures dr. edward lain has nothing to disclose. dr. doris day has participated in speaker programs for bausch health. dr. julie harper has received honoraria from aclaris, almirall, biopharmx, cassiopea, cutanea, dermira, foamix, galderma, laroche-posay, ortho dermatologics, and sun. dr. eric guenin is an employee of ortho dermatologics and may hold stock and/or stock options in its parent company. association between baseline disease characteristics and relapse-free survival in patients with braf v600–mutant resected stage iii melanoma treated with adjuvant dabrafenib + trametinib or placebo dirk schadendorf,1 reinhard dummer,2 axel hauschild,3 mario santinami,4 victoria atkinson,5 mario mandalà,6 vanna chiarion-sileni,7 james larkin,8 marta nyakas,9 caroline dutriaux,10 andrew haydon,11 laurent mortier,12 caroline robert,13 jacob schachter,14 christine-elke ortmann,15 egbert de jong15 eduard gasal,16 richard kefford,17 john m. kirkwood,18 georgina v. long19 1university hospital essen, essen, and german cancer consortium, heidelberg, germany; 2university hospital zürich skin cancer center, zürich, switzerland; 3university hospital schleswig-holstein, kiel, germany; 4fondazione istituto nazionale tumori, milano, italy; 5princess alexandra hospital, gallipoli medical research foundation, university of queensland, woolloongabba, qld, australia; 6papa giovanni xxiii cancer center hospital, bergamo, italy; 7melanoma oncology unit, veneto institute of oncology iov-irccs, padova, italy; 8the royal marsden nhs foundation trust, london, united kingdom; 9oslo university hospital, oslo, norway; 10centre hospitalier universitaire de bordeaux, hôpital saint-andré, bordeaux, france; 11the alfred hospital, melbourne, vic, australia; 12université de lille, inserm u 1189, chru lille, lille, france; 13gustave roussy and paris-sud-paris-saclay university, villejuif, france; 14ella lemelbaum institute for immuno-oncology and melanoma, sheba medical center, tel hashomer, and sackler school of medicine, tel aviv university, tel aviv, israel; 15novartis pharma ag, basel, switzerland; 16novartis pharmaceuticals corporation, east hanover, nj; 17macquarie university, melanoma institute australia, westmead hospital, and the university of sydney, sydney, nsw, australia; 18melanoma program, upmc hillman cancer center, university of pittsburgh, pittsburgh, pa; 19melanoma institute australia, the university of sydney, and royal north shore and mater hospitals, sydney, nsw, australia background • in the double-blind, randomized, phase 3 combi-ad trial (nct01682083), 12 months of adjuvant dabrafenib + trametinib led to significant improvement in relapse-free survival (rfs) and distant metastasis-free survival (dmfs) vs placebo (rfs hazard ratio [hr], 0.47; p < .001; dmfs hr, 0.51; p < .001) in patients with resected braf v600–mutant stage iii melanoma1,2 – in the dabrafenib + trametinib arm, 3and 4-year rfs rates were 59% and 54%, respectively1 – in the dabrafenib + trametinib arm, 3and 4-year dmfs rates were 71% and 67%, respectively1 • a cure-rate model estimated that treatment with dabrafenib + trametinib led to a 17% absolute increase in the proportion of patients who will remain relapse free long term1 • an interim analysis of overall survival (os) showed a clinically meaningful improvement with dabrafenib + trametinib vs placebo (hr, 0.57 [95% ci, 0.42-0.79])2 • the safety profile of the combination was consistent with that observed in patients with metastatic melanoma2 • based on these trial results, dabrafenib + trametinib has been approved by multiple regulatory agencies globally, including the us food and drug administration and european commission, for the treatment of patients with resected braf v600–mutant stage iii melanoma3-6 • previous subgroup analysis of rfs demonstrated similar treatment benefit favoring dabrafenib + trametinib regardless of baseline factors, including1: – disease stage (per american joint committee on cancer [ajcc] 7th and 8th editions) – micrometastases/macrometastases – ulceration of the primary tumor • we present an updated analysis evaluating the association between baseline disease characteristics and rfs to identify patient subgroups likely to benefit from adjuvant treatment methods • combi-ad was a randomized, phase 3 study of dabrafenib + trametinib in patients with completely resected stage iii braf v600e/k–mutant melanoma (figure 1)1,7 figure 1. study design n=870 treatment: 12 monthsa 1:1 r a n d o m i z a t i o n key eligibility criteria • completely resected, high-risk stage iiia (lymph node metastasis > 1 mm), iiib, or iiic cutaneous melanoma • braf v600e/k mutation • surgically free of disease ≤ 12 weeks before randomization • ecog performance status 0 or 1 • no prior radiotherapy or systemic therapy stratification • braf mutation status (v600e, v600k) • disease stage (ajcc 7; iiia, iiib, iiic) • primary endpoint: rfsd • secondary endpoints: os, dmfs, ffr, safety dabrafenib 150 mg bid + trametinib 2 mg qd (n = 438) 2 matched placebos (n = 432) follow-upb until end of studyc bid, twice daily; dmfs, distant metastasis–free survival; ecog, eastern cooperative oncology group; ffr, freedom from relapse; qd, once daily. a or until disease recurrence, death, unacceptable toxicity, or withdrawal of consent; b patients were followed up for disease recurrence until the first recurrence and thereafter for survival; c the study will be considered complete and final os analysis will occur when ≈ 70% of randomized patients have died or are lost to follow-up; d new primary melanoma considered as an event. analysis of the association of baseline factors with rfs • within each subgroup, the kaplan-meier method was used to estimate rfs, and hrs were calculated using a pike estimator – covariates including age, sex, t stage, n stage, in-transit metastases, and histological subtype were analyzed – tumor staging was assessed according to ajcc 7th edition criteria data set • analyses were based on the data cutoff date for an updated analysis of the combi-ad study (april 30, 2018) – minimum follow-up was 40 months for 870 enrolled patients (dabrafenib + trametinib, n = 438; placebo, n = 432) results • the median age of patients in combi-ad was 51 years. kaplanmeier analysis of rfs based on age (< median or ≥ median) demonstrated improved rfs in patients treated with dabrafenib + trametinib vs placebo regardless of age (figure 2) – age < 51 years: median rfs was not reached in the dabrafenib + trametinib arm vs 20.1 months in the placebo arm (hr, 0.51 [95% ci, 0.38-0.67]) – age ≥ 51 years: median rfs was not reached in the dabrafenib + trametinib arm vs 13.8 months in the placebo arm (hr, 0.49 [95% ci, 0.38-0.64]) figure 2. investigator-assessed kaplan-meier rfs curves by age 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 time from randomization, months p ro p o rt io n a liv e a n d r e la p se f re e 32 34 36 38 40 42 44 46 48 50 52 54 56 58 60 62 221 217 208 224 d+t < 51 y d+t ≥ 51 y pbo < 51 y pbo ≥ 51 y no. at risk 209 204 185 202 207 198 160 162 202 189 137 143 196 185 133 130 192 180 121 122 183 171 109 110 177 158 100 103 171 153 100 98 156 142 95 90 151 130 91 87 148 127 89 86 142 120 86 82 140 116 86 80 134 115 85 79 128 114 82 76 124 113 81 76 122 111 76 75 117 110 74 73 116 109 73 72 95 88 61 67 84 77 53 59 77 71 51 56 62 52 39 41 49 43 32 31 35 30 20 24 27 20 12 15 20 14 9 9 9 4 0 4 4 1 2 2 0 1 0 0 group events, n (%) median (95% ci), mo d+t < 51 y ≥ 51 y 86 (39) 91 (42) nr (45.6-nr) nr (33.2-nr) 0.51 (0.38-0.67) 0.49 (0.38-0.64) pbo < 51 y ≥ 51 y 116 (56) 138 (62) 20.1 (13.8-35.3) 13.8 (11.0-19.6) d+t vs pbo hr (95% ci)a data cutoff: april 30, 2018. d, dabrafenib; nr, not reached; pbo, placebo; t, trametinib. a hr was estimated using pike estimator. an hr < 1 indicates a lower risk with dabrafenib + trametinib than with placebo. • kaplan-meier analysis demonstrated that dabrafenib + trametinib improved rfs vs placebo regardless of patients’ sex (figure 3) – female patients: median rfs was not reached in the dabrafenib + trametinib arm vs 25.5 months in the placebo arm (hr, 0.56 [95% ci, 0.42-0.75]) – male patients: median rfs was not reached in the dabrafenib + trametinib arm vs 13.8 months in the placebo arm (hr, 0.45 [95% ci, 0.35-0.58]) figure 3. investigator-assessed kaplan-meier rfs curves by sex 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 time from randomization, months p ro p o rt io n a liv e a n d r e la p se f re e 32 34 36 38 40 42 44 46 48 50 52 54 56 58 60 62 194 244 193 239 d+t female d+t male pbo female pbo male no. at risk 182 231 176 211 179 226 148 174 172 219 130 150 167 214 124 139 162 210 116 127 157 197 105 114 149 186 101 102 144 180 98 100 134 164 94 91 127 154 93 85 123 152 92 83 118 144 90 78 113 143 88 78 108 141 88 76 103 139 85 73 101 136 85 72 100 133 80 71 98 129 77 70 98 127 76 69 84 99 65 63 73 88 56 56 62 86 56 51 48 66 42 38 39 53 33 30 32 33 23 21 21 26 14 13 18 16 9 9 9 4 2 2 5 0 0 2 2 1 0 0 group events, n (%) median (95% ci), mo d+t female male 78 (40) 99 (41) nr (43.6-nr) nr (41.5-nr) 0.56 (0.42-0.75) 0.45 (0.35-0.58) pbo female male 108 (56) 146 (61) 25.5 (13.8-49.8) 13.8 (11.0-19.4) d+t vs pbo hr (95% ci)a data cutoff: april 30, 2018. a hr was estimated using pike estimator. an hr < 1 indicates a lower risk with dabrafenib + trametinib than with placebo. • rfs benefit consistently favored dabrafenib + trametinib vs placebo across all t stages classified per ajcc 7th edition criteria (figure 4) – t1: median rfs was not reached in the dabrafenib + trametinib or placebo arms (hr, 0.42 [95% ci, 0.25-0.70]) – t2: median rfs was not reached in the dabrafenib + trametinib arm vs 22.1 months in the placebo arm (hr, 0.51 [95% ci, 0.34-0.76]) – t3: median rfs was 44.5 months in the dabrafenib + trametinib arm vs 16.6 months in the placebo arm (hr, 0.55 [95% ci, 0.390.77]) – t4: median rfs was 40.9 months in the dabrafenib + trametinib arm vs 8.6 months in the placebo arm (hr, 0.42 [95% ci, 0.29-0.60]) figure 4. investigator-assessed kaplan-meier rfs curves by t stage 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 time from randomization, months p ro p o rt io n a liv e a n d r e la p se f re e 32 34 36 38 40 42 44 46 48 50 52 54 56 58 60 62 74 108 140 106 83 102 128 106 d+t t1 d+t t2 d+t t3 d+t t4 pbo t1 pbo t2 pbo t3 pbo t4 no. at risk 70 102 133 99 79 92 120 85 70 100 128 98 69 78 98 69 68 98 125 91 62 70 85 55 67 95 121 90 56 67 81 51 67 94 117 87 54 62 71 48 65 91 112 81 51 55 65 42 63 87 104 76 49 50 60 38 60 85 100 74 49 50 57 36 56 77 90 70 44 48 54 33 53 73 87 65 43 47 50 32 52 72 85 63 43 46 49 31 52 68 80 59 41 44 46 31 50 67 78 58 41 42 46 31 50 63 77 56 41 41 45 31 49 62 73 55 41 38 45 29 49 61 70 54 41 38 45 28 49 59 69 53 40 37 43 26 48 59 68 49 40 35 42 25 48 59 67 48 40 34 41 25 46 48 47 39 33 31 34 25 38 44 44 32 28 26 31 22 36 38 41 30 27 25 29 21 28 31 29 24 19 20 23 15 23 27 21 19 16 15 18 12 19 18 13 13 11 11 13 8 12 13 11 9 8 5 7 6 9 7 10 6 4 3 7 3 1 3 5 3 1 0 1 2 1 1 2 0 1 1 0 0 0 1 0 1 0 0 t3 t4 63 (45) 49 (46) 44.5 (30.7-nr) 40.9 (26.8-nr) 0.55 (0.39-0.77) 0.42 (0.29-0.60) pbo t1 t2 38 (46) 57 (56) nr (16.6-nr) 22.1 (11.5-41.3) d+t t1 t2 18 (24) 42 (39) nr (nr-nr) nr (38.9-nr) 0.42 (0.25-0.70) 0.51 (0.34-0.76) group events, n (%) median (95% ci), mo t3 t4 77 (60) 75 (71) 16.6 (10.8-33.1) 8.6 (5.6-13.9) d+t vs pbo hr (95% ci)a data cutoff: april 30, 2018. a hr was estimated using pike estimator. an hr < 1 indicates a lower risk with dabrafenib + trametinib than with placebo. • rfs was longer with dabrafenib + trametinib than with placebo across all n stages classified per ajcc 7th edition criteria (figure 5) – n1: median rfs was not reached in the dabrafenib + trametinib arm vs 33.1 months in the placebo arm (hr, 0.52 [95% ci, 0.37-0.72]) – n2: median rfs was not reached in the dabrafenib + trametinib arm vs 12.2 months in the placebo arm (hr, 0.38 [95% ci, 0.280.53]) – n3: median rfs was 24.2 months in the dabrafenib + trametinib arm vs 7.1 months in the placebo arm (hr, 0.58 [95% ci, 0.41-0.83]) • rfs benefit favored dabrafenib + trametinib vs placebo regardless of the absence or presence of in-transit metastases (figure 6) – in patients without in-transit metastases, median rfs was not reached in the dabrafenib + trametinib arm vs 17.2 months in the placebo arm (hr, 0.49 [95% ci, 0.40-0.60]) – in patients with in-transit metastases, median rfs was 45.6 months in the dabrafenib + trametinib arm vs 5.7 months in the placebo arm (hr, 0.45 [95% ci, 0.24-0.82]) figure 5. investigator-assessed kaplan-meier rfs curves by n stage 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 time from randomization, months p ro p o rt io n a liv e a n d r e la p se f re e 32 34 36 38 40 42 44 46 48 50 52 54 56 58 60 62 169 159 110 176 158 97 d+t n1 d+t n2 d+t n3 pbo n1 pbo n2 pbo n3 no. at risk 163 148 102 169 139 78 161 144 100 151 112 58 155 140 96 130 100 50 151 138 92 127 89 47 147 135 90 119 82 42 143 128 83 111 70 38 134 123 78 104 63 36 129 120 75 101 62 35 121 112 65 95 57 33 115 106 60 91 55 32 113 103 59 90 53 32 110 100 52 86 51 31 107 99 50 86 50 30 105 96 48 85 49 30 103 94 45 81 48 29 101 91 45 80 48 29 99 90 44 76 48 27 96 89 42 74 47 26 96 88 41 72 47 26 78 70 35 64 40 24 71 60 30 53 36 23 66 53 29 50 36 21 52 37 25 41 25 14 48 24 20 30 21 12 34 16 15 21 16 7 22 13 12 14 7 6 18 7 9 8 5 5 7 2 4 2 0 2 2 0 3 1 1 0 2 0 1 0 0 n3 64 (58) 24.2 (19.3-40.8) 0.58 (0.41-0.83) pbo n1 n2 90 (51) 98 (62) 33.1 (19.6-57.9) 12.2 (8.3-17.3) d+t n1 n2 56 (33) 57 (36) nr (nr-nr) nr (47.9-nr) 0.52 (0.37-0.72) 0.38 (0.28-0.53) group events, n (%) median (95% ci), mo -n3 65 (67) 7.1 (5.4-12.8) d+t vs pbo hr (95% ci)a data cutoff: april 30, 2018. a hr was estimated using pike estimator. an hr < 1 indicates a lower risk with dabrafenib + trametinib than with placebo. figure 6. investigator-assessed kaplan-meier rfs curves by status of in-transit metastases 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 time from randomization, months p ro p o rt io n a liv e a n d r e la p se f re e 32 34 36 38 40 42 44 46 48 50 52 54 56 58 60 62 387 51 395 36 d+t: no d+t: yes pbo: no pbo: yes no. at risk 367 46 359 27 362 43 302 19 352 39 262 17 342 39 246 16 334 38 227 15 318 36 205 13 300 35 190 12 291 33 185 12 269 29 173 11 254 27 166 11 248 27 163 11 236 26 156 11 230 26 154 11 225 24 152 11 218 24 146 11 213 24 145 11 209 24 139 11 203 24 136 10 202 23 134 10 163 20 119 8 144 17 104 7 132 16 99 7 102 12 76 4 82 10 60 3 58 7 41 3 40 7 24 3 29 5 16 2 11 2 3 1 5 0 2 0 2 1 0 0 group events, n (%) median (95% ci), mo d+t no yes 153 (40) 24 (47) nr (nr-nr) 45.6 (19.1-nr) 0.49 (0.40-0.60) 0.45 (0.24-0.82) pbo no yes 229 (58) 25 (69) 17.2 (13.8-23.7) 5.7 (2.8-34.1) d+t vs pbo hr (95% ci)a data cutoff: april 30, 2018. a hr was estimated using pike estimator. an hr < 1 indicates a lower risk with dabrafenib + trametinib than with placebo. figure 7. investigator-assessed kaplan-meier rfs curves by histological subtype (superficial spreading, nodular, other) 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 time from randomization, months p ro p o rt io n a liv e a n d r e la p se f re e 32 34 36 38 40 42 44 46 48 50 52 54 56 58 60 62 191 102 145 173 119 139 d+t superficial spreading d+t nodular d+t other pbo superficial spreading pbo nodular pbo other no. at risk 181 98 134 160 105 121 179 97 129 132 90 99 173 93 125 113 76 90 170 90 121 108 72 82 168 88 116 102 71 69 161 82 111 95 64 59 151 78 106 87 60 55 149 76 99 87 57 53 136 71 91 83 50 51 131 66 84 81 47 49 128 65 82 80 46 48 124 62 76 78 43 46 122 60 74 77 42 46 118 58 73 75 42 46 115 57 70 73 41 43 114 55 68 73 40 43 114 52 67 71 38 41 111 51 65 70 36 40 110 51 64 69 35 40 92 36 55 58 31 38 77 33 51 50 29 33 73 32 43 49 28 30 57 25 32 39 21 20 49 22 21 31 19 13 34 16 15 21 13 10 25 11 11 15 6 6 19 6 9 10 5 3 6 1 6 1 3 0 1 1 3 1 1 0 0 2 0 1 0 0 other 62 (43) 47.9 (28.8-nr) 0.49 (0.36-0.69) pbo superficial spreading nodular 93 (54) 77 (65) 24.4 (13.8-52.9) 16.5 (11.1-22.1) d+t superficial spreading nodular 66 (35) 49 (48) nr (nr-nr) 45.6 (28.8-nr) 0.48 (0.35-0.66) 0.53 (0.37-0.75) group events, n (%) median (95% ci), mo -other 84 (60) 11.0 (8.4-20.2) d+t vs pbo hr (95% ci)a data cutoff: april 30, 2018. a hr was estimated using pike estimator. an hr < 1 indicates a lower risk with dabrafenib + trametinib than with placebo. • dabrafenib + trametinib improved rfs vs placebo regardless of histological subtype (figure 7) – in patients with nodular melanoma, median rfs was 45.6 months in the dabrafenib + trametinib arm vs 16.5 months in the placebo arm (hr, 0.53 [95% ci, 0.37-0.75]) – in patients with superficial spreading melanoma, median rfs was not reached in the dabrafenib + trametinib arm vs 24.4 months in the placebo arm (hr, 0.48 [95% ci, 0.35-0.66]) conclusions • rfs benefit favored dabrafenib + trametinib in patients with completely resected stage iii braf v600e/k– mutant melanoma vs placebo regardless of the following baseline factors, confirming previous findings1: – age – sex – t stage – n stage – status of in-transit metastases – histological subtype • this updated analysis supports the use of dabrafenib + trametinib regardless of clinical and pathological factors at treatment initiation references 1. hauschild a, et al. j clin oncol. 2018;36:3441-3449. 2. long gv, et al. n engl j med. 2017;377:1813-1823. 3. tafinlar (dabrafenib) [package insert]. east hanover, nj: novartis pharmaceuticals corporation; 2018. 4. mekinist (trametinib) [package insert]. east hanover, nj: novartis pharmaceuticals corporation; 2018. 5. tafinlar (dabrafenib) [summary of product characteristics]. camberley, uk: novartis pharmaceuticals uk ltd; 2018. https://www.ema.europa.eu/en/documents/product-information/tafinlar-eparproduct-information_en.pdf. accessed april 18, 2019. 6. mekinist (trametinib) [summary of product characteristics]. camberley, uk: novartis pharmaceuticals uk ltd; 2019. https://www.ema.europa.eu/en/documents/product-information/mekinist-eparproduct-information_en.pdf. accessed april 18, 2019. 7. dummer r, et al. esmo 2018 [poster 1250p]. acknowledgments we thank the patients and their families for their participation. we also thank study site staff, additional investigators, and others for their contributions. we thank maurizio voi, md (novartis pharmaceuticals corporation), for guidance and critical review and jorge j. moreno-cantu, msc, phd (novartis pharmaceuticals corporation), for editorial assistance. this study was sponsored by glaxosmithkline; dabrafenib and trametinib are assets of novartis ag as of march 2, 2015. we thank zareen khan, phd, from articulatescience llc, for medical editorial assistance with this presentation, which was funded by novartis pharmaceuticals corporation, east hanover, nj, in accordance with good publication practice (gpp3) (https://www.ismpp.org/gpp3) guidelines and international committee of medical journal editors recommendations. this was previously presented at the 2019 american society of clinical oncology annual meeting text: qf6c35 to: 8nova (86682) us only +18324604729 north, central and south americas; caribbean; china +447860024038 uk, europe & russia +46737494608 sweden, europe scan this qr code copies of this poster obtained through quick response (qr) code are for personal use only and may not be reproduced without permission from asco® and the author of this poster. visit the web at: http://novartis.medicalcongressposters.com/default.aspx?doc=f6c35 presented at winter clinical derm 2023, january 13–18, 2023 (encore of previous presentation at the european society of medical oncology [esmo] 2022, september 8–13, hughes bgm et al.). reused with permission. phase 2 confirmatory study of cemiplimab (350 mg iv q3w) in patients with locally advanced or metastatic cutaneous squamous cell carcinoma (cscc): study 1540 group 6 brett gm hughes,1 jean-jacques grob,2 samantha e bowyer,3 fiona day,4 rahul ladwa,5 brian stein,6 eva muñoz-couselo,7 nicole basset-seguin,8 alexander guminski,9 laurent mortier,10 axel hauschild,11 michael r migden,12 chrysalyne d schmults,13 suk-young yoo,14 jocelyn booth,14 frank seebach,15 israel lowy,15 matthew g fury,15 danny rischin16 1royal brisbane and women’s hospital and the university of queensland, brisbane, australia; 2aix marseille university, hôpital de la timone, marseille, france; 3faculty of health and medical sciences, the university of western australia and department of medical oncology, sir charles gairdner hospital, perth, australia; 4department of medical oncology, calvary mater newcastle, newcastle, australia; 5princess alexandra hospital, woolloongabba, australia; 6adelaide cancer centre, adelaide, australia; 7vall d’hebron university hospital, medical oncology department, melanoma and other skin tumors unit, vall d’hebron institute of oncology (vhio), barcelona, spain; 8hôpital saint-louis, paris, france; 9department of medical oncology, royal north shore hospital, st leonards, australia; 10dermatology clinic, caraderm and university of lille, inserm u1189, lille hospital-claude huriez hospital, lille cedex, france; 11department of dermatology, university hospital (uksh), kiel, germany; 12departments of dermatology and head and neck surgery, university of texas md anderson cancer center, houston, tx, usa; 13department of dermatology, brigham and women’s hospital, harvard medical school, boston, ma, usa; 14regeneron pharmaceuticals, inc., basking ridge, nj, usa; 15regeneron pharmaceuticals, inc., tarrytown, ny, usa; 16department of medical oncology, peter maccallum cancer centre, melbourne, australia introduction • cscc is the second most common malignancy in the us, accounts for 20% of skin cancer cases, and results in 1 million cases per year, with the incidence continuing to rise 50–200% annually within the last three decades.1 • surgical excision is most commonly used and provides most patients a favorable prognosis; unfortunately the recurrence rate of cscc is higher than with other cancers and the development of locally advanced (lacscc) or metastatic disease (mcscc) occurs in a number of these cases.2,3 • the discovery of the programmed cell death-1 (pd-1) receptor and its associated ligands programmed cell death-ligand 1 (pd-l1) and programmed cell death-ligand 2 (pd-l2) in tumors has offered a new direction for clinical cancer immunotherapies in targeting anti–pd-1/pd-l1.4 • cemiplimab is a high-affinity, fully human, hinge-stabilized immunoglobulin g4 anti–pd-l1 antibody that blocks the interaction of pd-1 receptor with its ligands, pd-l1 and pd-l2.5 • in the phase 1 (nct02383212) and the pivotal phase 2 (nct02760498) clinical trials, cemiplimab was the first systemic therapy to demonstrate significant antitumor activity in patients with advanced cscc.6-9 • here, we report additional efficacy and safety data from the pivotal phase 2 trial that examined the group 6 patients with advanced cscc undergoing cemiplimab monotherapy, 350 mg every 3 weeks (q3w) for up to 108 weeks. objective • the primary objective was to assess the clinical benefits of cemiplimab by measuring the objective response rate (orr; complete response [cr] + partial response [pr]) per independent central review (icr). • the secondary objectives were to report the duration of response (dor), progression-free survival (pfs), and overall survival (os) by central and investigator review. safety and tolerability of cemiplimab are also reported. methods • empower-cscc-1 is an open-label, non-randomized, multicenter, international phase 2 study of patients with advanced cscc (nct02760498). • at data cutoff date of october 25, 2021, 167 patients ≥18 years old with histologically confirmed metastatic or unresectable lacscc were enrolled in the study. • the patients enrolled were treated with cemiplimab 350 mg intravenous or with the option to switch to subcutaneous dosing, for up to 108 weeks. results patients • a total of 167 patients were enrolled with a median age of 76.0 years (range, 40–94). most patients had a primary cancer site of the head and neck (n=113, 67.7%) (table 1). • 165 of 167 patients received at least one dose of cemiplimab and were followed up for a median of 8.71 months (range, 0.0–19.5). the median duration of exposure was 35.7 weeks (range, 0.9–86.9). • orr, cr and pr analysis were performed with the total number of 164 patients, excluding patients who did not receive cemiplimab (n=2) or had no baseline tumor assessment due to covid-19 (n=1). • five of 167 patients received prior systemic therapies (0.03%). conclusions • group 6 in the empower-cscc-1 study demonstrated a safety and efficacy profile that was consistent with the previously reported clinical trial experience for groups 1, 2, and 3 of the study. • cemiplimab remains a standard-of-care option in patients with advanced cscc who are not candidates for curative surgery or radiation. acknowledgments the authors thank the patients who participated in this study. medical writing and editorial support under the direction of the authors was provided by tingting griffin, phd, of prime (knutsford, uk) and funded by regeneron pharmaceuticals, inc., and sanofi according to good publication practice guidelines. responsibility for all opinions, conclusions and data interpretation lies with the authors. disclosure brett gm hughes reports serving on an advisory board for amgen, bristol-myers squibb, merck sharp & dohme, roche, sanofi, eisai, pfizer, astrazeneca and takeda; and research grants from amgen. references 1. waldman a et al. hematol oncol clin north am. 2019;33:1–12. 2. que skt et al. j am acad dermatol. 2018;78:237–247. 3. stratigos aj et al. eur j cancer. 2020;128:60–82. 4. sunshine j et al. curr opin pharmacol. 2015;23:32–38. 5. burova e et al. mol cancer ther. 2017;16:861–870. 6. migden mr et al. lancet oncol. 2020;21:294–305. 7. migden mr et al. n engl j med. 2018;379:341–351. 8. rischin d et al. j immunother cancer. 2021;9. 9. rischin d et al. j immunother cancer. 2020;8. response • tumor response per icr, median pfs and os remained generally consistent with the previous update (data cutoff, october 11, 2020) (table 2). • the median orr was 45.1% (74/164; 95% confidence interval [ci], 37.4%, 53.1%) with cr in 5.5% (9/164) and pr in 39.6% (65/164) (table 2). • as of the data cutoff date of october 25, 2021, the median dor was not reached (95% ci, 13.0 months, not evaluable [ne]) (table 2, figure 1). • among treated patients, the median pfs was 14.7 months (95% ci, 10.4, ne) and the median os was not reached (95% ci, 17.6 months, ne) (table 2, figure 2). table 1. patient demographics and baseline characteristics characteristic advanced cscc (n=167) age, median (range), years 76.0 (40–94) male, n (%) 130 (77.8) ecog performance status, n (%) 0 67 (40.1) 1 98 (58.7) missing 2 (1.2) primary cscc site: head and neck, n (%) 113 (67.7) metastatic cscc, n (%) 100 (59.9) locally advanced cscc, n (%) 67 (40.1) duration of exposure to cemiplimab, median (range), weeks 35.7 (0.9–86.9) number of cemiplimab doses administered, median (range) 11.0 (1–29) cscc, cutaneous squamous cell carcinoma; ecog, eastern cooperative oncology group. table 2. tumor response per icr patients, n advanced cscc cemiplimab: 350 mg q3w (group 6) duration of follow-up, median (range), months 165§ 8.71 (0.0–19.5) orr, % (95% ci) 164† 45.1 (37.4–53.1) cr, n (%) 9 (5.5) pr, n (%) 65 (39.6) dor, median (95% ci), months 74‡ nr (13.0–ne) pfs, median (95% ci), months 165§ 14.7 (10.4–ne) os, median (95% ci), months 165§ nr (17.6–ne) †the total number of patients in the tumor response analysis was 164, excluding patients who did not receive cemiplimab (n=2) or had no baseline tumor assessment due to covid-19 (n=1). ‡full analysis set: patients with confirmed cr or pr (n=74). §full analysis set: group 6 patients who received at least one dose of cemiplimab (n=165). ci, confidence interval; cr, complete response; dor, duration of response; ne, not evaluable; nr, not reached; orr, objective response rate; os, overall survival; pfs, progression-free survival; pr, partial response; q3w, every 3 weeks. table 3. teaes advanced cscc (n=165) teaes, n (%) any grade grade ≥3 any 163 (98.8) 75 (45.5) serious 72 (43.6) 57 (34.5) leading to discontinuation 23 (13.9) 12 (7.3) leading to death 14 (8.5) 14 (8.5) any-grade teaes occurring in ≥10% of patients, n (%) fatigue 43 (26.1) diarrhea 35 (21.2) pruritus 35 (21.2) nausea 28 (17.0) asthenia 23 (13.9) arthralgia 22 (13.3) constipation 19 (11.5) decreased appetite 19 (11.5) rash maculo-papular 17 (10.3) most common grade ≥3 teaes, n (%) hypertension 6 (3.6) pneumonia 6 (3.6) general physical health deterioration 5 (3.0) adverse events were coded according to the preferred terms of the medical dictionary for regulatory activities, version 22.1. the severity of adverse events was graded according to the national cancer institute common terminology criteria for adverse events, version 4.03. cscc, cutaneous squamous cell carcinoma; teae, treatment emergent adverse event. figure 1. kaplan-meier curve of dor per icr 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 0 2 4 6 8 10 12 14 16 18 20 22 24 74 73 62 50 34 21 14 5 1 0 0 0 0 p ro b a b ili ty o f n o p ro g re s s io n o r d e a th month advanced cscc cemiplimab 350 mg q3w (group 6) group advanced cscc cemiplimab 350 mg q3w (group 6) number of patients at risk cscc, cutaneous squamous cell carcinoma; dor, duration of response; icr, independent central review; q3w, every 3 weeks. figure 2. kaplan-meier curves of pfs and os per icr 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 0 2 4 6 8 10 12 14 16 18 20 22 24 165 138 108 98 82 57 36 20 8 1 0 0 0 p ro b a b ili ty o f p f s (a) (b) month advanced cscc cemiplimab 350 mg q3w (group 6) 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 0 2 4 6 8 10 12 14 16 18 20 22 24 165 152 143 139 113 79 59 34 17 6 0 0 0 p ro b a b ili ty o f s u rv iv a l month advanced cscc cemiplimab 350 mg q3w (group 6) number of patients at risk number of patients at risk group advanced cscc cemiplimab 350 mg q3w (group 6) group advanced cscc cemiplimab 350 mg q3w (group 6) cscc, cutaneous squamous cell carcinoma; icr, independent central review; os, overall survival; pfs, progression-free survival; q3w, every 3 weeks. safety • of 165 patients that received at least one dose of cemiplimab, 163 (98.8%) experienced at least one treatment-emergent adverse event (teae) of any grade regardless of attribution (table 3). • the most common teae of any grade was fatigue (n=43, 26.1%), followed by diarrhea (n=35, 21.2%), pruritus (n=35, 21.2%) and nausea (n=28, 17.0%). • grade ≥3 teaes were reported in 75 patients (45.5%), the most common being hypertension (n=6, 3.6%) and pneumonia (n=6, 3.6%), followed by general physical health deterioration (n=5, 3.0%). • in total, 16 patients (9.7%) experienced at least one grade ≥3 immune-related adverse event based on investigator assessment, with the most common being adrenal insufficiency (n=2, 1.2%). • overall, 23 patients (13.9%) discontinued treatment due to possibly treatment-related teaes of any grade, with those resulting in death reported in 14 cases (8.5%) in group 6. – none of the deaths were considered to be related to cemiplimab. the fatal aes were due to: covid-19–related events (n=2), other infection (n=4), sudden death not otherwise specified without autopsy (n=2), myocardial infarction, gastrointestinal bleed, pulmonary embolism, acute myelogenous leukemia, and declining mental status in setting of morphine patient-controlled analgesia and pulmonary edema, and meningitis that was likely infectious (n=1 each). scan the qr code for co-author disclosures skin september 2017 volume 1 issue 2 copyright 2017 the national society for cutaneous medicine 74 in-depth reviews common adverse drug-drug interactions in dermatology: oral therapies joanna dong, ba, lauren bonomo, ba, mark lebwohl, md a a icahn school of medicine at mount sinai, department of dermatology, new york, new york pharmacotherapy in dermatology can be especially complex and challenging: the wide array of comorbidities that patients present to care with and the spectrum of systemic oral therapies that are commonly prescribed in a standard dermatology practice increase the likelihood of adverse drug-drug interactions. such interactions can range from neutralized drug efficacy to fatal adverse effects and are most commonly due to the potentiation or antagonism of cytochrome p450 metabolism or competitive renal excretion by an offending drug to affect the pharmacokinetics of concurrently dosed drugs. drug-drug interactions can contribute to up to 60% of adverse drug reactions seen in the inpatient or immediate discharge setting, representing a potentially significant iatrogenic source of preventable healthcare costs, morbidity, and mortality in patient care. 1,2 we review here the most common systemic treatments causing drug-drug interactions in standard dermatology practice. methotrexate (mtx) acts through inhibition of dihydrofolate reductase and thymidylate synthetase, reducing folate formation and impairing dna synthesis/repair, respectively. it is used at high doses in standard chemotherapy regimens and at low doses in psoriasis, crohn disease, rheumatoid arthritis, and other autoimmune conditions. toxicities, which can occur at all doses, include myelosuppression, hepatotoxicity, renal impairment, and pneumonitis. a near total reliance on renal excretion without production of inactive metabolites makes mtx vulnerable to drug-drug interactions when kidney function is affected. 3 in fact, mtx represents the highest severity of drug-drug interactions of all medications prescribed in the outpatient setting. 4 drug-drug interactions between systemic oral therapies in dermatology can result in preventable iatrogenic causes of patient morbidity and mortality. most of these interactions are due to cytochrome p450 or renal excretion interactions. we review here a number of drugs and drug-drug interactions seen in general dermatology, including methotrexate, bexarotene, macrolides, cyclosporine, epinephrine, isotretinoin, spirinolactone, allopurinol, and oral contraceptives. introduction abstract methotrexate skin september 2017 volume 1 issue 2 copyright 2017 the national society for cutaneous medicine 75 trimethoprim-sulfamethoxazole (tmp-smx), which also inhibits folate synthesis, can interact with mtx to severe systemic adverse events through multi-fold proposed mechanisms: 1) potentiated inhibition of dihydrofolate reductase impairs folate production and causes myelosuppression 2) sulfamethoxazole and mtx are both nephrotoxic and can cause a positive feedback loop of impaired kidney excretion, leading to further elevated levels of both drugs. in a systemic analysis of 1 case-control study and 17 case reports, concurrent mtx and tmp-smx was a risk factor for pancytopenia, occurring notably at low doses (5 to 15 mg per week) of mtx. 5 there were no consistent hepatic, renal, or pulmonary findings across the literature but the authors advised caution in patients with preexisting kidney conditions. the link between increased nephrotoxicity and concurrent mtx and tmpsmx use still remains to be definitively investigated, even at high dose mtx. 6 the interaction between nsaids and mtx has long been investigated, with at least 30 cases and studies in the literature. 5 the proposed mechanism is competitive renal tubular excretion, thereby increasing serum mtx levels. high-dose mtx has well-documented interaction with nsaids, causing myelosuppression, transaminitis, and acute kidney injury. overall, indomethacin, diclofenac, ibuprofen, and high-dose aspirin has shown propensity to interact with mtx while incidences involving naproxen, probenecid, flurbiprofen, piroxicam, ketoprofen, metamizole, and low-dose aspirin were rare. 5 this is in contrast to the interaction between low-dose mtx with nsaids, which exhibits pharmacokinetic interaction but with minimal clinical significance. 7 a cochrane review of inflammatory arthritis patients concluded the relatively safe concurrent use of nsaids (including etodolac, celecoxib, and etoricoxib) with mtx in this clinical setting, except for high-dose aspirin, which can precipitate hepatic and renal problems. 8 acitretin replaced etretinate in the treatment of keratinizing disorders due to high lipophilicity of etretinate and its subsequent presence in adipose tissue after cessation for up to 3 years. 9 with a significantly shorter half-life 10 , acitretin is the preferred therapeutic option given the teratogenic potential of both compounds and a shorter recommended contraception period after treatment cessation of acitretin. however, alcohol can cause ethyl esterification of acitetretin to etretinate, likely related to ethanol metabolism to acetyl coenzyme a, an activator of etretinate production from acitretin. 11 in patients with concomitant alcohol use of 150 to 200 g or more during acitretin treatment, etretinate was detectable in a dose-dependent manner with alcohol intake for up to 57 days after acitretin discontinuation, compared to no etretinate found in patients without alcohol consumption. 11,12 as a result of this interaction and the widespread use and presence of alcohol in consumer products, the recommended contraceptive and pregnancy avoidance period after acitretin treatment is now extended to 3 years in the us. patients should further be cautioned to maintain alcohol abstinence during therapy and for at least 2 months after stopping acitretin. bexarotene, a selective retinoid x receptor agonist used in cutaneous t cell lymphoma, acitretin bexarotene skin september 2017 volume 1 issue 2 copyright 2017 the national society for cutaneous medicine 76 is metabolized by cytochrome p450 3a4 (cyp3a4) and is, thus, susceptible to interactions with drugs that induce or inhibit cyp3a4. because of the high incidence of hypertriglyceridemia and risk of pancreatitis, patients on bexarotene are typically started on lipid-lowering agents. fibrates are first-line therapy in this context to specifically target triglyceride levels. gemfibrozil is the only fibrate contraindicated with concurrent bexarotene use due its potent inhibition of cyp3a4, increasing serum levels of bexarotene and causing extreme hypertriglyceridemia. in a study of 54 patients receiving bexarotene, 2 of 3 patients taking concurrent gemfibrozil had incidences of hypertriglyceridemia-related pancreatitis while patients taking other lipid-lowering agents had no incidences of pancreatitis. 13 macrolide antibiotics can interact, to varying degrees, with numerous common drugs due to its inhibition of the cyp3a4 metabolic pathway and a promotile effect that may enhance the enteric absorption of drugs. 14 the three most commonly prescribed macrolides exhibit varying propensities to inhibit cyp3a4 and cause drug interactions: erythromycin most strongly, clarithromycin less so, and azithromycin has no effect on cyp3a4. 14 for example, erythromycin and clarithromycin, but not azithromycin, interact with statins to increase the relative risk of rhabdomyolysis and acute kidney injury by two-fold. 15 other medications that can interact with macrolides, particularly erythromycin, include triazolam, pimozide, cisapride, quinidine, warfarin, cyclosporine, theophylline, carbamazepine, and antihistamines. 16 interactions involving erythromycin should be avoided due to risk of precipitation of qt prolongation, torsades de pointes, and other fatal arrhythmias. patients using erythromycin and concurrent cyp3a4 inhibitors had 5 times the rate of sudden deaths from cardiac causes compared to patients taking erythromycin without concurrent cyp3a4 inhibitors. 17 the association between azithromycin and cardiovascular death remains controversial and further studies, particularly in the context of specific drug interactions, are necessary before any conclusions can be made. 18.19 cyclosporine has as extensive a list of side effects, which include nephrotoxicity, hypertension, hypomagnesemia, hyperkalemia, hyperlipidemia, hypertrichosis, and lymphoproliferative disease, as interacting drugs, owing to its inhibition of multiple metabolic players, including cyp3a4, organic anion transporting polypeptides (oatp), multidrug resistanceassociated protein 2 (mrp2), and multidrug resistance protein 1 (mdr1). 20.21 aminoglycosides, erythromycin, tmp-smx, calcium channel blockers, antifungals, cimetidine, ranitidine, carbamazepine, phenytoin, rifampin, and phenobarbital, all cyp3a4-metabolized, should be used concurrently with caution. statins are frequently used for cyclosporine-induced hyperlipidemia. statins undergo discrete metabolic pathways: lovastatin, simvastatin, and atorvastatin are primarily oxidized by cyp3a4, while pravastatin, fluvastatin, rosuvastatin, and pitavastatin are affected by perturbation of oatp and other transporters. 22-24 due to the widespread effects of cyclosporine on multiple metabolizing proteins, it has a uniquely observed pharmacokinetic impact on all statins, increasing area macrolides cyclosporine skin september 2017 volume 1 issue 2 copyright 2017 the national society for cutaneous medicine 77 under concentration-time curve (auc) by 2 to 20-fold, though the clinical significance is not to be overstated. 24 while the concurrent use of cyclosporine and statins can lead to myopathy and rhabdomyolysis, statins at low doses may be safely used with cyclosporine. 24 further, statins do not appear to pharmacokinetically perturb plasma concentrations of cyclosporine. 25 the potentially fatal interaction between epinephrine-based local anesthetic and betablockers was described in a case series of 6 patients on daily propranolol who exhibited hypertensive crises and subsequent bradycardia after in-office administration of 1:100,000 or 1:200,000 of epinephrine. 26 the mechanism underlying this interaction rests on epinephrine's effect as both a vasoconstrictor and vasodilator due to its agonism of α1 (vasoconstriction of skin and mucous blood vessels), β1 (increases heart rate and contractility), and β2 receptors (vasodilation of skeletal muscle blood vessels). concurrent epinephrine and betablockers, particularly non-selective betablockers, can precipitate potent alphareceptor effects, leading to hypertension and reflex bradycardia. levonordefrin and norepinephrine have significantly decreased or no β2 receptor activity, and thus have higher risk of this interaction, as evidenced in the literature. 27,28 the non-selective blockers propranolol and pindolol have demonstrated propensity to interact with epinephrine, while cardioselective blockers (β1 only) do not induce hypertension with concomitant epinephrine. 2830 this interaction appears to occur in a dosedependent manner with epinephrine levels. 30 many of these aforementioned cases and studies took place in the plastic or dental surgery context, which require large amounts of epinephrine compared to dermatologic procedures. it is likely that the doses of epinephrine used in the dermatologic and mohs setting is insufficient to induce hypertensive episodes, though use should be optimally minimized in patients on daily nonselective beta-blockers. 31 oral isotretinoin is a vitamin a analogue primarily used in the treatment of severe acne vulgaris. common side effects include cheilitis, xerosis, and increased photosensitivity while rare and serious side effects include myalgia, depression, and pseudotumor cerebri. 32 due to well-known teratogenic properties, isotretinoin must be accompanied by effective contraception when used in females of reproductive age. because tetracycline antibiotics, particularly doxycycline and minocycline, are also used to treat acne vulgaris, their interaction with isotretinoin is of vital importance in dermatologic practice. pseudotumor cerebri, a condition in which intracranial hypertension may mimic signs and symptoms of a brain mass such as papilledema, visual disturbances, nausea, vomiting, headaches, and tinnitus, can be caused by concurrent tetracycline and isotretinoin use. 33 if left unrecognized and untreated, this can lead to permanent vision loss. it is thought that this occurs due to effects on cyclic adenosine monophosphate, causing decreased cerebrospinal fluid outflow at the arachnoid villi level. 34 this interaction can induce pseudotumor cerebri in as few as 3 weeks. 35 therefore, combination therapy with these agents is not recommended. fortunately, a history of prior use of oral tetracyclines in the majority of patients who begin oral isotretinoin do not appear at risk of epinephrine isotretinoin skin september 2017 volume 1 issue 2 copyright 2017 the national society for cutaneous medicine 78 developing intracranial hypertension. 36 in fact, there is evidence that oral isotretinoin can safely be used in patients who have developed pseudotumor cerebri while on tetracyclines in the past. 37 nonetheless, it is important to monitor these patients for signs and symptoms of increased intracranial pressure, as early intervention greatly improves the prognosis of this condition. spironolactone is a potassium-sparing diuretic used in dermatology for the treatment of hormonal acne. 38 it achieves its diuretic and hormonal effects through androgen and mineralocorticoid receptor antagonism, the latter of which inhibits aldosterone and decreases potassium excretion in the cortical collecting duct of the nephron. while its “potassium-sparing” effect is sometimes desired, it also increases the risk of hyperkalemia, which can be precipitated or exacerbated by the addition of other medications, particularly tmx-smp and renin-angiotensin inhibitors. tmx-smp is known to increase the risk of hyperkalemia in patients taking spironolactone, resulting in up to a 12-fold increased risk of hospital admission for patients on this combination. 39 the mechanism by which this occurs is impaired potassium secretion due to an amiloride-like inhibition of sodium channels in the luminal membrane of the distal tubule. a populationbased, nested case-control study of 328 canadian patients on spironolactone found an increased risk of sudden death among those who received trimethoprimsulfamethoxazole versus ampicillin. 40 a similar pattern of hyperkalemia has been observed in older adults on a combination of spironolactone and a renin-angiotensin axis inhibitor (ace inhibitors or angiotensin receptor blockers). this is likely has the same mechanism and is more commonly seen in real-life practice than in clinical trials. 41 it is crucial to note that all of these studies focused on older adults. the majority of patients prescribed spironolactone by a dermatologist are otherwise healthy, premenopausal women. the necessity of potassium monitoring in this population is questionable, as recent evidence suggests that the rate of hyperkalemia in healthy young women taking spironolactone is equal to the baseline rate of hyperkalemia in this population. 42 nevertheless, when clinically appropriate, alternative antibiotics and antihypertensive agents should be chosen for these patients. allopurinol, a xanthine oxidase inhibitor used in maintenance of gout, has extensive interactions with other drugs, the most serious of which are with azathioprine and 6mercaptopurine. these two medications are metabolized by xanthine oxidase, and coadministration with allopurinol without dose adjustment can cause potentially fatal pancytopenia. 43 however, azathioprine and allopurinol combination therapy at reduced doses has proven to be a safe and effective treatment option for patients with inflammatory bowel disease. 44 allopurinol has other important interactions, including several with dermatologic manifestations. ampicillin is thought to cause more frequent drug rashes when taken alongside allopurinol, evidenced from the boston collaborative drug surveillance program, established in 1966. 45,46 since then, no large-scale confirmatory studies have been performed. however, a recent report showed hypersensitivity symptoms, including an extensive, erythematous, papular eruption, with amoxicillin, a related penicillin-derivative, spironolactone allopurinol skin september 2017 volume 1 issue 2 copyright 2017 the national society for cutaneous medicine 79 in a patient with previous adverse reaction to allopurinol. 47 the authors attribute this to a possible co-sensitization. it is therefore best to avoid these two antibiotics whenever possible in patients taking allopurinol, particularly in patients with a history of adverse dermatologic reaction to allopurinol. the concurrent use of oral contraceptives (ocs) and oral antibiotics remain in a longstanding debate over the extent of clinically significant interaction. it is known that rifampin increases the metabolism of ocs, leading to sub-contraceptive concentrations of oc steroids. 49 anecdotal reports of pregnancy occurring on antibiotics used in dermatologic practice suggested that lowdose tetracyclines may have a similar effect. 50 however, no pharmacokinetic studies have detected a change in plasma levels of ocs with tetracycline antibiotics. 51 additionally, a large case-crossover study demonstrated that antibiotic use in dermatologic practice does not increase the risk of accidental pregnancy on ocs. 52 the authors did find that a few individual patients showed significant decreases in oc concentration while taking tetracyclines. because there is currently no way to predict which individuals will exhibit this effect, it is still appropriate to use caution when prescribing ocs and oral antibiotics simultaneously and recommend a second or alternate form of birth control, such as condoms or intra-uterine devices, in patients who do not desire pregnancy. interactions involving mtx, acitretin, bexarotene, macrolides, cyclosporine, epinephrine, isotretinoin, spirinolactone, allopurinol, and ocs may be commonly seen in dermatology practice and can lead to severe systemic effects. thorough medication reconciliation and cautious use of interacting drugs are important to avoid these preventable drug-drug interactions. conflict of interest disclosures: none. funding: none. corresponding author: mark lebwohl, md 5 e 98th st, 5th floor new york, ny 10029 tel: 212-241-9728 email: mark.lebwohl@mountsinai.org references: 1. egger ss, drewe j, schlienger rg. potential drug-drug interactions in the medication of medical patients at hospital discharge. eur j clin pharmacol. 2003;58(11):773-8. 2. jankel ca, fitterman lk. epidemiology of drug-drug interactions as a cause of hospital admissions. drug saf. 1993;9(1):51-9. 3. bannwarth b, pehourcq f, schaeverbeke t, dehais j. clinical pharmacokinetics of lowdose pulse methotrexate in rheumatoid arthritis. clin pharmacokinet. 1996;30(3):194210. 4. toivo tm, mikkola ja, laine k, airaksinen m. identifying high risk medications causing potential drug-drug interactions in outpatients: a prescription database study based on an online surveillance system. res social adm pharm. 2016;12(4):559-68. 5. bourre-tessier j, haraoui b. methotrexate drug interactions in the treatment of rheumatoid arthritis: a systematic review. j rheumatol. 2010;37(7):1416-21. 6. chan aj, rajakumar i. high-dose methotrexate in adult oncology patients: a case-control study assessing the risk association between drug interactions and methotrexate toxicity. j oncol pharm pract. 2014;20(2):93-9. 7. hall jj, bolina m, chatterley t, jamali f. interaction between low-dose methotrexate and nonsteroidal anti-inflammatory drugs, oral contraceptives conclusion skin september 2017 volume 1 issue 2 copyright 2017 the national society for cutaneous medicine 80 penicillins, and proton pump inhibitors. ann pharmacother. 2017;51(2):163-78. 8. colebatch an, marks jl, edwards cj. safety of non-steroidal anti-inflammatory drugs, including aspirin and paracetamol (acetaminophen) in people receiving methotrexate for inflammatory arthritis (rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, other spondyloarthritis). cochrane database syst rev. 2011(11):cd008872. 9. rollman o, vahlquist a. retinoid concentrations in skin, serum and adipose tissue of patients treated with etretinate. br j dermatol 1983;109(4):439-47. 10. larsen fg, jakobsen p, eriksen h, gronhoj j, kragballe k, nielsen-kudsk f. the pharmacokinetics of acitretin and its 13-cismetabolite in psoriatic patients. j clin pharmacol. 1991;31(5):477-83. 11. larsen fg, jakobsen p, knudsen j, weismann k, kragballe k, nielsen-kudsk f. conversion of acitretin to etretinate in psoriatic patients is influenced by ethanol. j invest dermatol. 1993;100(5):623-7. 12. gronhoj larsen f, steinkjer b, jakobsen p, hjorter a, brockhoff pb, nielsen-kudsk f. acitretin is converted to etretinate only during concomitant alcohol intake. br j dermatol. 2000;143(6):1164-9. 13. talpur r, ward s, apisarnthanarax n, breuermcham j, duvic m. optimizing bexarotene therapy for cutaneous t-cell lymphoma. j am acad dermatol. 2002;47(5):672-84. 14. von rosensteil na, adam d. macrolide antibacterials. drug interactions of clinical significance. drug saf. 1995;13(2):105-22. 15. patel am, shariff s, bailey dg, juurlink dn, gandhi s, mamdani m, et al. statin toxicity from macrolide antibiotic coprescription: a population-based cohort study. ann intern med. 2013;158(12):869-76. 16. 16. westphal jf. macrolide induced clinically relevant drug interactions with cytochrome p450a (cyp) 3a4: an update focused on clarithromycin, azithromycin and dirithromycin. br j clin pharmacol. 2000;50(4):285-95. 17. 17. ray wa, murray kt, meredith s, narasimhulu ss, hall k, stein cm. oral erythromycin and the risk of sudden death from cardiac causes. n engl j med. 2004;351(11):1089-96. 18. svanstrom h, pasternak b, hviid a. use of azithromycin and death from cardiovascular causes. n engl j med. 2013;368(18):1704-12. 19. ray wa, murray kt, hall k, arbogast pg, stein cm. azithromycin and the risk of cardiovascular death. n engl j med. 2012;366(20):1881-90. 20. bramow s, ott p, thomsen nielsen f, bangert k, tygstrup n, dalhoff k. cholestasis and regulation of genes related to drug metabolism and biliary transport in rat liver following treatment with cyclosporine a and sirolimus (rapamycin). pharmacol toxicol. 2001;89(3):133-9. 21. shitara y, itoh t, sato h, li ap, sugiyama y. inhibition of transporter-mediated hepatic uptake as a mechanism for drug-drug interaction between cerivastatin and cyclosporin a. j pharmacol exp ther. 2003;304(2):610-6. 22. schachter m. chemical, pharmacokinetic and pharmacodynamic properties of statins: an update. fundam clin pharmacol. 2005;19(1):117-25. 23. cohen lh, van leeuwen re, van thiel gc, van pelt jf, yap sh. equally potent inhibitors of cholesterol synthesis in human hepatocytes have distinguishable effects on different cytochrome p450 enzymes. biopharm drug dispos. 2000;21(9):353-64. 24. neuvonen pj, niemi m, backman jt. drug interactions with lipid-lowering drugs: mechanisms and clinical relevance. clin pharmacol ther. 2006;80(6):565-81. 25. asberg a, hartmann a, fjeldsa e, bergan s, holdaas h. bilateral pharmacokinetic interaction between cyclosporine a and atorvastatin in renal transplant recipients. am j transplant. 2001;1(4):382-6. 26. foster ca, aston sj. propranolol-epinephrine interaction: a potential disaster. plast reconstr surg. 1983;72(1):74-8. skin september 2017 volume 1 issue 2 copyright 2017 the national society for cutaneous medicine 81 27. mito rs, yagiela ja. hypertensive response to levonordefrin in a patient receiving propranolol: report of case. j am dent assoc. 1988;116(1):55-7. 28. hjemdahl p, akerstedt t, pollare t, gillberg m. influence of beta-adrenoceptor blockade by metoprolol and propranolol on plasma concentrations and effects of noradrenaline and adrenaline during i.v. infusion. acta physiol suppl. 1983;515:45-53. 29. rehling m, svendsen tl, maltbaek n, tango m, trap-jensen j. haemodynamic effects of atenolol, pindolol and propranolol during adrenaline infusion in man. eur j clin pharmacol. 1986;30(6):659-63. 30. houben h, thien t, van 't laar a. effect of low-dose epinephrine infusion on hemodynamics after selective and nonselective beta-blockade in hypertension. clin pharmacol ther. 1982;31(6):685-90. 31. dzubow lm. the interaction between propranolol and epinephrine as observed in patients undergoing mohs' surgery. j am acad dermatol. 1986;15(1):71-5. 32. lester rs, schachter gd, light mj. isotretinoin and tetracycline in the management of severe nodulocystic acne. international journal of dermatology. int j dermatol. 1985;24(1):252-7. 33. friedman di. medication-induced intracranial hypertension in dermatology. am j clin dermatol. 2005;6(1):29-37. 34. chiu am, chuenkongkaew wl, cornblath wt, trobe jd, digre kb, dotan sa, musson kh, eggenberger er. minocycline treatment and pseudotumor cerebri syndrome. am j ophthalmol. 1998;126(1):116-21. 35. lee ag. pseudotumor cerebri after treatment with tetracycline and isotretinoin for acne. cutis. 1995;55(3):165-8. 36. nagler ar, milam ec, orlow sj. the use of oral antibiotics before isotretinoin therapy in patients with acne. j am acad dermatol. 2016;74(2):273-9. 37. bettoli v, borghi a, mantovani l, scorrano r, minghetti s, toni g, sarno o, zauli s, virgili a. safe use of oral isotretinoin after pseudo-tumor cerebri due to minocycline. eur j dermatol. 2012;21(6):1024-5. 38. saint-jean m, ballanger f, nguyen jm, khammari a, dréno b. importance of spironolactone in the treatment of acne in adult women. j eur acad dermatol venereol. 2011;25(12):1480-1. 39. antoniou t, gomes t, mamdani mm, yao z, hellings c, garg ax, weir ma, juurlink dn. trimethoprim-sulfamethoxazole induced hyperkalaemia in elderly patients receiving spironolactone: nested case-control study. bmj. 2011;343:d5228. 40. antoniou t, hollands s, macdonald em, gomes t, mamdani mm, juurlink dn. trimethoprim–sulfamethoxazole and risk of sudden death among patients taking spironolactone. cmaj. 2015;187(4):e138-43. 41. abbas s, ihle p, harder s, schubert i. risk of hyperkalemia and combined use of spironolactone and long‐term ace inhibitor/angiotensin receptor blocker therapy in heart failure using real‐life data: a population‐and insurance‐based cohort. pharmacoepidemiol drug saf. 2015;24(4):40613. 42. plovanich m, weng qy, mostaghimi a. low usefulness of potassium monitoring among healthy young women taking spironolactone for acne. jama dermatol. 2015;151(9):941-4. 43. gearry rb, day as, barclay ml, leong rw, sparrow mp. azathioprine and allopurinol: a two-edged interaction. j gastroenterol hepatol. 2010;25(4):653-5. 44. leung y, sparrow mp, schwartz m, hanauer sb. long term efficacy and safety of allopurinol and azathioprine or 6mercaptopurine in patients with inflammatory bowel disease. j crohns colitis. 2009;3(3):162-7. 45. jick h, slone d, shapiro s. excess of ampicillin rashes associated with allopurinol or hyperuricemia. n engl j med. 1972;286:505-7. 46. jick h, porter jb. potentiation of ampicillin skin reactions by allopurinol or hyperuricemia. j clin pharmacol. 1981;21(10):456-8. skin september 2017 volume 1 issue 2 copyright 2017 the national society for cutaneous medicine 82 47. ben fredj n, aouam k, chaabane a, toumi a, ben rhomdhane f, boughattas n, chakroun m. hypersensitivity to amoxicillin after drug rash with eosinophilia and systemic symptoms (dress) to carbamazepine and allopurinol: a possible co-sensitization. br j clin pharmacol. 2010;70(2):273-6. 48. jones j, mosher w, daniels k. current contraceptive use in the united states, 2006–2010, and changes in patterns of use since 1995. natl health stat report. 2012;60:1-25. 49. dickinson bd, altman rd, nielsen nh, sterling ml. drug interactions between oral contraceptives and antibiotics. ostet gynecol. 2001;98(5):853-60. 50. helms se, bredle dl, zajic j, jatjoura d, brodell rt, krishnarao i. oral contraceptive failure rates and oral antibiotics. j am acad dermatol. 1997;36(5):705-10. 51. archer js, archer df. oral contraceptive efficacy and antibiotic interaction: a myth debunked. j am acad dermatol. 2002;46(6):917-23. 52. toh s, mitchell aa, anderka m, hernándezdíaz s, study nb. antibiotics and oral contraceptive failure—a case-crossover study. contraception. 2011;83(5):418-25. microsoft word july 2020 scom 718 proof returned .docx skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 386 short communications a 65-year-old male with a large plaque of retiform purpura with impending necrosis on the right lower abdomen itohan h. omorodion, mph1, richard h. flowers, md, faad1, thomas g. cropley, md, faad1 1department of dermatology, university of virginia, charlottesville, va a 65-year-old male patient presented to dermatology as a referral from neurology clinic for concern of an injection site reaction. the patient had a history of multiple sclerosis treated for the past eight years with glatiramer acetate (ga) (copaxone ®) 40 mg/ml via self-injection 3 times weekly to the thighs and abdomen. three weeks prior to presentation, he experienced pain and erythema of the right lower abdomen immediately after an injection of ga. the patient had experienced a similar reaction of pain and swelling of his right thigh after a previous administration of ga five years before. on examination, he had a large plaque of retiform purpura with impending necrosis on the right lower abdomen, clinically diagnostic of nicolau syndrome (figure 1). nicolau syndrome (ns) is a rare but highly distinctive adverse reaction to intramuscular, intra-articular, or subcutaneous injections which can lead to ischemic necrosis of the skin, muscle, and adipose tissue.1,2 ns has been reported following injections of various medications, including nonsteroidal antiinflammatory drugs, antibiotics, glucocorticoids, and anesthetics.2,3 in this report, the patient experienced ns after selfinjecting ga after approximately 8 years of prior ga therapy. there are other published reports of ns associated with ga, and reactions may occur years after starting ga.1,2,4 the clinical presentation of ns is intense pain at the injection site immediately after administration, erythema and reticular or livedoid purpuric changes within a few hours, and necrotic ulceration within a few days that can progress into a scar in a few weeks.1,4 the pathophysiology of ns likely involves ischemic damage from a thromboembolic occlusion or direct vascular injury that subsequently leads to occlusion.3 when diagnosing ns, it is also important to consider other vasculopathic conditions resulting from thrombotic or embolic occlusions. relevant conditions to distinguish ns from are myxoma emboli, cholesterol emboli, necrotizing fasciitis, and calcific medial arteriolopathy (calciphylaxis).3 myxoma or cholesterol emboli would be more likely to cause livedo changes in the bilateral distal lower extremities rather than at an injection site.3 necrotizing fasciitis is more likely to present with a rapidly spreading, severely painful necrotic plaque in a febrile patient.3 biopsy may be necessary when the diagnosis is unclear but usually is not needed. skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 387 figure 1. (a) edematous, erythematous patch at the site of subcutaneous glatiramer acetate (ga) injection on the right lower abdomen, immediately following injection. (b) after one week, a large plaque of retiform purpura is seen. (c) after 20 days, the plaque is resolving with a dry necrotic slough. supportive management is the main treatment of ns and can include dressings, topical steroids, anticoagulation, analgesics, and antibiotics. in the present case, conservative wound management with topical mupirocin and dry dressings were utilized with slow resolution of the reaction. in extreme cases, surgical debridement may be indicated.1,3,4 ns is mainly attributed to improper injection technique and the risk of recurrence is low, so it is not a contraindication for continuing therapy.1,4 ns may be avoided by using z-track injections, long needles, auto-injectors, performing aspirations prior to injection, and injecting in regions with less blood vessels.3 our patient did not resume glatiramer therapy and four months later, his multiple sclerosis remained stable. in conclusion, we present a rare but distinct reaction to injected glatiramer known as nicolau syndrome. this reaction as such is likely underrecognized, and we seek to highlight its classical presentation scenario. conflict of interest disclosures: none funding: none corresponding author: itohan h. omorodion 1215 lee st charlottesville, va 22908 phone: 540-498-8476 fax: 434-924-5936 email: iho5gp@virginia.edu references 1. mott se, peña zg, spain ri, white kp, ehst bd. nicolau syndrome and localized panniculitis: a report of dual diagnoses with an emphasis on morphea profunda-like changes following injection with glatiramer acetate. j cutan pathol. 2016;43(11):1056-1061. 2. gulseren d, sahin eb, bozdogan o, artuz f. an avoidable adverse drug reaction: nicolau syndrome. int wound j. 2017;14(2):440-441. 3. tabor d, bertram cg, williams ajk, mathers me, biswas a. nicolau syndrome (embolia cutis medicamentosa): a rare and poorly recognized iatrogenic cause of cutaneous thrombotic vasculopathy. am j dermatopathol. 2018;40(3):212-215. 4. zecca c, mainetti c, blum r, gobbi c. recurrent nicolau syndrome associated with subcutaneous glatiramer acetate injection---a case report. bmc neurol. 2015;15(1):249. microsoft word july 2020 dh 795 proof returned.docx skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 391 dermatologic history hermann pinkus – influencing an entire generation of dermatopathologists joshua m. brady, bs,1 reem kashlan, mph,1 meena moossavi, md, mph1 1wayne state university, detroit, mi hermann pinkus was born in berlin, germany on november 18, 1905. his father was felix pinkus, a renowned professor, dermatologist, and dermatopathologist, who was a trail blazer in dermatology and poured decades of work into the field. felix was known for describing the structure of the hair follicle and lichen nitidus. hermann and his father, like many other jewish physicians in the 1930’s, were displaced from germany due to the nazi regime.1 hermann pinkus graduated from the university of berlin in 1929 and completed a majority of his training in breslau, germany. dr. pinkus then completed a fellowship in experimental cell research at the university of michigan, and went on to complete additional training in dermatopathology at wayne county general hospital in detroit. he established pinkus labs in 1944, which continues to be a well-respected dermatopathology lab. dr. pinkus became chairman of the department of dermatology at wayne state university for a decade, where he had a lasting impact on the residency program.1 in 1957, he pioneered a histological characterization of alopecia mucinosa. the fibroepithelioma of pinkus, a variant of basal cell carcinoma, was also first described by hermann pinkus in 1953.1 dr. pinkus described the eccrine poroma, which he posited was a benign tumor with a histologic resemblance to the epidermal eccrine sweat duct. he coined the term “acrosyringium,” describing a name for the epidermal sweat duct unit.1 additionally, dr. pinkus brought forward many more original findings and paved the way for future research in dermatopathology. skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 392 dr. pinkus was a founding member of the american society of dermatopathology and held the position of vice president of the american dermatological association. in 1969, he published his textbook entitled a guide to dermatohistopathology. dr. pinkus’ visionary textbook was known by many as the best dermatopathology textbook at the time of its publication.1 esteemed dermatopathologist, a. bernard ackerman, explained that although hermann made a massive impact on the field himself, “if one considers both, father and son, no pair made more significant contributions to dermatology and dermatopathology than felix and hermann pinkus.”2 conflict of interest disclosures: none funding: none corresponding author: meena moossavi, md, mph wayne state university school of medicine department of dermatology 18100 oakwood boulevard, suite 300 dearborn, mi 48124 phone: 313-240-4900 email: mmoossav@wayne.edu references: 1. löser c, plewig g, burgdorf whc. pantheon of dermatology: outstanding historical figures. springer berlin heidelberg; 2013: 869-876. 2. weyers w. hermann pinkus an appreciation on the occasion of his 100th birthday. dermatopathol pract concept. 2006;12(1). acknowledgements: medical writing support was provided by prescott medical communications group (chicago, il) with financial support from ortho dermatologics | presented at the fall clinical dermatology conference • october 17-20, 2019 • las vegas, nv synopsis ◾ quality of life (qol) in patients with acne has been shown to correlate more strongly with patient-reported severity than physician-reported severity, suggesting that patient perception may be important to consider during acne treatment1 ◾ compared with other dermatologic conditions, acne is associated with greater negative psychosocial impacts, particularly with feelings of despair and distress2 ◾ acne-related qol has been shown to be worse in women, possibly because of differences in perceptions regarding self-appearance and cosmetic concerns2 ◾ the first lotion formulation of tretinoin, developed by utilizing novel polymeric emulsion technology,3 has been evaluated in two phase 3 studies that included male and female patients with moderate-to-severe acne (nct02932306, nct02965456)4 objective ◾ to determine potential improvements in qol with tretinoin 0.05% lotion and assess potential gender differences in these outcomes in a post hoc analysis of the pooled data from these two phase 3 studies methods ◾ data were pooled from two multicenter, randomized, double-blind, vehicle-controlled studies in which participants were randomized (1:1) to receive tretinoin 0.05% lotion or vehicle, once-daily for 12 weeks • during these studies, cerave® hydrating cleanser and cerave® moisturizing lotion (l’oreal, ny) were provided as needed for optimal moisturization/cleaning of the skin ◾ qol was assessed using the validated acne-qol questionnaire in 4 different domains (self-perception, role-emotional, role-social, acne symptoms) ◾ in addition, participants completed a patient satisfaction survey (pss) at baseline and week 12 to assess satisfaction with previous acne therapy using a 10-point scale, where 10=most satisfied results ◾ the pooled population included 1640 participants (tretinoin, n=819; vehicle, n=821), 909 (55.4%) of whom were female; participants’ ages ranged from 9 to 58 years ◾ mean pss scores at baseline were 4.7 and 4.6 for tretinoin 0.05% lotion and vehicle, respectively, indicating similar satisfaction with prior acne treatment • at week 12, satisfaction was significantly greater with tretinoin 0.05% lotion vs vehicle (7.2 vs 6.6, p<0.001) ◾ acne-qol scores at baseline indicated impairment in all domains (figure 1), with lower (worse) mean scores in female participants as follows: self-perception (2.6 vs 3.5 for males); role-emotional (2.6 vs 3.4); role-social (3.5 vs 4.1); acne symptoms (2.7 vs 3.2; figure 2) • mean scores for all domains increased (improved) significantly by week 12 (p<0.001) in the overall population • while domain scores in the male participants remained significantly greater compared to those in female participants, changes from baseline in the female participants were much greater (figures 2 and 3) • at week 12, mean scores for self-perception, role-emotional, role-social and acne symptoms were 4.3 (65% improvement), 4.2 (62%), 4.8 (37%), and 4.1 (52%) in females, compared to 4.8 (37%), 4.6 (35%), 5.2 (27%), and 4.4 (38%) in males (figure 3) acne-related quality of life: efficacy of a novel tretinoin 0.05% lotion in male and female patients with moderate-to-severe disease sharleen st. surin-lord, md1,2; william philip werschler, md3; eric guenin, pharmd, phd, mph4 1visage dermatology and aesthetic center, visage clinical research, largo, md; 2howard university college of medicine, washington, dc; 3university of washington, school of medicine, seattle, wa; 4ortho dermatologics, bridgewater, nj figure 1: average acne-qol domain scores at baseline for all participants in the tretinoin 0.05% lotion or vehicle treatment groups (itt population; pooled data) 2.75 5.00 4.75 4.50 4.25 4.00 3.75 3.50 3.25 3.00 5.25 m e a n s co re ( 9 5 % c i) acne quality of life domains tretinoin lotion vehicle lotion self-perception role-emotional role-social acne symptoms acne-qol, acne-specific quality of life questionnaire; itt, intent-to-treat. figure 2: average acne-qol domain scores at baseline for males and females in the tretinoin 0.05% lotion group (itt population; pooled data) 2.25 5.00 4.75 4.50 4.25 4.00 3.75 3.50 3.25 3.00 2.75 2.50 5.50 5.25 m e a n s co re ( 9 5 % c i) acne quality of life domains male female self-perception role-emotional role-social acne symptoms acne-qol, acne-specific quality of life questionnaire; itt, intent-to-treat. figure 3: average acne-qol domain scores at week 12 for males and females in the tretinoin 0.05% lotion group (itt population; pooled data) 2.25 5.00 4.75 4.50 4.25 4.00 3.75 3.50 3.25 3.00 2.75 2.50 5.50 5.25 m e a n s co re ( 9 5 % c i) acne quality of life domains male female self-perception role-emotional role-social acne symptoms acne-qol, acne-specific quality of life questionnaire; itt, intent-to-treat. conclusion ◾ tretinoin 0.05% lotion was significantly more effective than its vehicle in achieving improvements in qol, especially in female participants ◾ improvements seen in each qol domain were mirrored by a significant improvement in participant satisfaction references 1. martin ar, et al. clin exp dermatol. 2001;26(5):380-385. 2. gorelick j, et al. j dermatol nurses assoc. 2015;7(3):154-162. 3. kircik lh, et al. j drugs dermatol. 2019;18(4):s148-154. 4. tyring sk, et al. j drugs dermatol. 2018;17(10):1084-1091. author disclosures dr. sharleen st. surin-lord is a paid speaker for galderma and pfizer, and a paid consultant for bausch health. dr. william philip werschler has served as an investigator for ortho dermatologics. dr. eric guenin is an employee of ortho dermatologics. powerpoint presentation non-invasive genomic profiling in pediatric patients allyson g. perry, phd1, danielle ruppenthal, pa-c1, kellie hill, cls (ascp)1 presented at the winter clinical dermatology conference january 13-18, 2023 1. dermtech, 11099 north torrey pines road, suite 150 la jolla, ca 92037, usa 1. gerami p, yao z, polsky d, et al. development and validation of a noninvasive 2-gene molecular assay for cutaneous melanoma. j am acad dermatol. 2017;76(1):114120.e2. 2. jackson sr, jansen b, yao z, ferris lk. risk stratification of severely dysplastic nevi by non-invasively obtained gene expression and mutation analyses. skin the journal of cutaneous medicine. 2020;4(2):105-110. 3. tracy et, aldrink jh. pediatric melanoma. semin pediatr surg. oct 2016;25(5):290298. references funding/disclaimer: the authors are employed by dermtech. conclusion scan qr code for additional peer-reviewed publications regarding this genomic test while overall pla positivity rates were similar across adult and pediatric samples, the proportion positive only for linc was more than two times higher in pediatric samples than the adult samples. tert promoter mutations are rare in lesions from pediatric patients. further investigation of the significance of linc, prame, and tert abnormalities in lesions from pediatric patients is ongoing. background: pigmented lesions with clinical features suspicious for melanoma are not uncommon in pediatric patients. evaluation of these lesions is complicated by the low prevalence of pediatric melanoma and challenges associated with performing biopsies in children. the dermtech melanoma test (‘the test’) is a non-invasive genomic test designed to rule out melanoma. it consists of the pigmented lesion assay (pla), which detects rna gene expression of long intergenic non-coding rna 00518 (linc00518, or linc) and preferentially expressed antigen in melanoma (prame), and an add-on assay for dna promoter mutations in telomerase reverse transcriptase (tert), which is performed if ordered and if sufficient genomic material is available. patients younger than 18 years were not included in initial validation studies. in this analysis, we sought to compare genomic biomarker results between uncertain pigmented lesions from adult and pediatric patients. methods: de-identified samples submitted to the clinical lab for the test from may through october 2022 were used for this analysis. genomic results were available for 36,377 samples. the anatomic locations of the lesions were categorized as head/neck, trunk, or extremities and compared between adult and pediatric patients. positivity rates for the pla (and each individual marker) and the tert add-on assay were calculated for adults and patients younger than 18 years of age. results: the pla was performed on 34,050 skin samples from adults and 2,327 samples from pediatric patients. there were no differences between adults and pediatric patients in anatomic location of the lesions tested. the proportion of pla-positive samples was similar between adult (7.0%, n=2,393) and pediatric (8.0%, n=187) patients. rates of biomarkers detected among pla-positive adult and pediatric patient samples, respectively, were as follows: linc only (31.4% vs 69.5%), prame only (45.5% vs 14.4%), linc and prame (23.0% vs 16.0%). the tert add-on assay was performed in 11,084 samples from adults and 613 samples from pediatric patients. of these, tert was positive in 830 (7.5%) adult and 3 (0.5%) pediatric patient samples. conclusions: this analysis provides new information about genomic profiling of uncertain pigmented lesions from pediatric patients. while overall pla positivity rates were similar across adult and pediatric samples, the proportion positive only for linc was more than two times higher in pediatric samples. additionally, tert promoter mutations were rarely detected in pediatric samples. further investigation of the significance of linc, prame, and tert abnormalities in lesions from pediatric patients is ongoing. abstract pre-biopsy genomic testing is used by providers to non-invasively rule out melanoma in uncertain pigmented lesions.1,2 since melanoma is rare in children, validation studies for the test excluded pediatric patients.1-3 however, pigmented lesions with concerning clinical features are not uncommon in children, in which biopsies can be particularly challenging to perform.3 the noninvasive nature of genomic testing is attractive for facilitating selection of the subset of pediatric lesions that are appropriate for biopsy. the test consists of the pigmented lesion assay (pla), which detects rna gene expression of linc00518 (linc) and prame, and an add-on assay for dna promoter mutations in tert, which is performed if ordered and if sufficient genomic material is available. the test is positive if one or more genomic markers are detected.1,2 the objective of this analysis was to compare genomic biomarker results between uncertain pigmented lesions from adult and pediatric patients. methods between may and october 2022, skin samples were collected using adhesive patches and submitted, along with patient age and anatomic location of the lesion, to the clinical lab for genomic profiling. samples were assessed for linc00518 and prame rna (qpcr), and in cases with sufficient material, dna mutations in the tert promoter region (sanger sequencing). deidentified samples were categorized by anatomic location (head/neck, trunk, or extremities) and age (pediatric: <18 years, adult: ≥18 years). positivity rates for the pla (and each individual marker) and the tert add-on assay were calculated and compared between adult and pediatric samples. results in total, 34,050 adult and 2,327 pediatric samples underwent pla analysis. anatomic locations of the lesions tested were similar between age groups, with the lesions on the trunk accounting for just over 50% of lesions tested (table 1). introduction and objective table 1. the anatomic locations of 5 samples (4 adult, 1 pediatric) were not specific enough to be assigned to a category. adult (≥18 years) n=34,046 pediatric (<18 years) n=2,326 anatomic location n % n % trunk 17,921 52.6% 1,265 54.4% extremities 8,432 24.8% 554 23.8% head and neck 7,693 22.6% 507 21.8% overall positivity rates for the pla were similar between adult (7.0%, n=2,393) and pediatric (8.0%, n=187) samples. of pla-positive samples, the proportion positive for linc alone was higher in pediatric samples (69.5%) compared to adult samples (31.4%) (table 2). the tert add-on assay was performed on 11,084 adult and 613 pediatric samples. tert mutations were detected in 7.5% of adult and 0.5% of pediatric samples (table 3). adult (≥18 years) n=34,050 pediatric (<18 years) n=2,327 pla results n % n % negative 31,657 93.0% 2,140 92.0% positive 2,393 7.0% 187 8.0% linc only 752 31.4% 130 69.5% prame only 1,090 45.5% 27 14.4% linc and prame 551 23.0% 30 16.0% table 2. adult (≥18 years) n=11,084 pediatric (<18 years) n=613 tert results n % n % negative 10,254 92.5% 610 99.5% positive 830 7.5% 3 0.5% tert only 616 74.2% 1 33.3% linc, prame, tert 120 14.5% 1 33.3% prame, tert 66 8.0% 0 0.0% linc, tert 28 3.4% 1 33.3% table 3. slide number 1 powerpoint presentation understanding flares in pediatric and adolescent patients with moderate or severe atopic dermatitis: a real-world study in the united states and europe lawrence f eichenfield1, vivian y shi2, jiade yu3,4, evangeline j pierce5, amber reck atwater5, jenny austin6, phoebe salmon6, james piercy6, peter anderson6, amy s paller7 1. departments of dermatology and pediatrics, university of california san diego school of medicine and rady children’s hospital san diego; 2. department of dermatology, university of arkansas for medical sciences; 3. department of dermatology massachusetts general hospital; 4. harvard medical school; 5. eli lilly and company, indianapolis, usa ; 6. adelphi real world, bollington, uk; 7. department of dermatology, northwestern university feinberg school of medicine, chicago, usa methods study design background / synopsis ■ atopic dermatitis (ad) is a chronic heterogeneous inflammatory skin disorder characterised by pruritus and eczematous lesions ■ ad has a fluctuating disease pattern with many patients experiencing acute exacerbations often referred to as ‘flares’1.2 ■ currently, real-world data on pediatric and adolescent (≤17 years) ad are limited, with the impact of the reported disease burden, including flares, largely unquantified objective ■ the objective of this study is to better understand flaring in patients <17 years old with moderate or severe ad conclusions ■ just over 60% of moderate and severe patients with ad, aged <17 years, experience flares, the large majority having experienced multiple flares during the past year. a typical flare for moderate or severe patients lasted two weeks ■ ad flares cause a moderate to high degree of bother in both moderate and severe patients although greater in patients with severe ad ■ these findings suggest that controlling flares could lead to a lower burden of disease key eligibility criteria physician inclusion criteria: – primary care practitioners / pediatricians / dermatologists / allergists – actively involved in drug management of patients <17 years old with ad – minimum monthly workload of • for pcps / pediatricians: – >4 ad patients, aged <17 years (≥1 ever mild, ≥1 mild with history of moderate/severe ad, ≥1 moderate) • for dermatologist / allergists / immunologists: – >6 ad patients, aged <17 years (≥1 mild with history of moderate/severe ad, ≥3 moderate, ≥1 severe). study was sponsored by eli lilly and company patient inclusion criteria (for this analysis): – <17 years old – physician diagnosis of ad – currently assessed to have moderate or severe ad – not currently involved in a clinical trial. additional methods ■ data were drawn from the adelphi pediatric ad disease specific programme3, a retrospective cross-sectional realworld study conducted in the united states, france, germany, italy, spain and the united kingdom between february and june 2019 ■ physicians provided information on clinical characteristics including current overall disease severity (physician determination of mild, moderate, or severe ad) as well as severity, number, and duration of flares ■ flares were defined in the physician completed patient record forms as “acute episodes = flares, temporary worsening of symptoms” ■ patients, or their parent/guardian, were invited to complete a patient self-completion questionnaire (psc) reporting the degree of bother for “times when your skin gets much worse’” (extremely, very, moderately, a little, or not at all bothered by flares) ■ for this analysis “very/extremely” were defined as a high degree of bother and “a little/not at all” as low degree of bother table 1. patient demographics and clinical characteristics winter clinical dermatology conference; hawaii, usa; january 13-18, 2023 scan or click the qr code or use this url (https://lillyscience.lilly.com/congress/wcdc2023) for a list of all lilly content presented at the congress. other company and product names are trademarks of their respective owners. moderate patients (n=1005) severe patients (n=762) demographics mean age, years (sd) 9.9 (5.0) 11.2 (5.0) male gender, % 50.5 55.2 mean bmi (sd), kg/m2 19.8 (6.3) 20.7 (8.6) race: white, % 76.7 76.9 clinical characteristics time since diagnosis, years (sd) 3.4 (3.6) 4.3 (4.3) those with type ii comorbidity, % 46.8 60.2 bsa currently, % 18.6 32.2 easi (range 0-72) 9.2 20 results ■ a total of 390 physicians (49 pcps; 90 pediatricians; 210 dermatologists; 41 allergists) provided records for 2570 patients of whom 1005 were considered currently moderate and 762 currently severe (table 1). 803 currently mild patients were excluded ■ 427 moderate and 304 severe patients or their parent/guardian completed a psc ■ for 60.1% of moderate patients and 62.4% of severe patients, the physician reported the patient had suffered acute episodes (flares) as part of their disease pattern; 53.7% of moderate and 57.1% of severe patients experienced 1 or more flares during the last 12 months (fig 1) ■ of those with flares in the last 12 months, moderate patients suffered a median [interquartile range] of 2[2-3] flares and severe patients suffered a median of 3[2-4] (fig 2) ■ moderate patients were more likely to have mild or moderate flares (determined by physicians) while severe patients had more moderate and severe flares (fig 2) ■ the median duration of a typical flare for both moderate and severe patients was 14 days (fig 3) ■ 64.5% of severe patients self-reported the degree of bother of flares as high, 21.1% reported moderate bother and 14.5% reported low bother. for moderate patients, 38.6% reported a high degree of bother, 29.7% moderate bother and 31.6% low bother (fig 4) figure 4. patient-reported degree of bother during times when their skin gets much worse key results figure 1. physician-reported flares among moderate and severe patients figure 3. physician-reported median [iqr] duration of flares (days) over the last 12 months iqr: interquartile range references 1. girolomoni g and busà vm. ther adv chronic dis. 2022; 13:1-19 2. sidbury r et al. j am acad dermatol. 2014; 71(6): 1218–1233. 3. anderson p et al. curr med res opin. 2008;24(11):3063-7 disclosures  le, vs, and ap are in receipt of consultancy payments with eli lilly and company  ep and ara are employees of eli lilly and company  ja, ps, jp and pa are employees of adelphi real world  the dsp is a wholly owned adelphi real world multi-subscriber product. eli lilly and company is one of a number subscribers to the dsp.  this study is previously presented at fall clinical dermatology conference (fall cdc 2022); hybrid / las vegas, usa; 20-23 october 2022 type ii comorbidity: allergic contact dermatitis, allergic rhinitis, alopecia areata, angioedema, atopic keratoconjunctivitis, asthma, nasal polyps, other allergic conditions, urticaria, vitiligo figure 2. physician-reported median [iqr] number of flares over the last 12 months iqr: interquartile range slide number 1 skin march 2020 volume 4 issue 2 180 copyright 2020 the national society for cutaneous medicine short communications tnfα antagonist induced bullous pemphigoid: a case report aderonke obayomi md mph1, garrett vick md1, tamela charbonnet md2 1tulane university school of medicine department of dermatology, new orleans, la 2family dermatology specialisits, metairie, la this is a case of a 73-year-old caucasian female with diabetes mellitus type 2, graves’ disease, and a 4-month long history of severe plaque psoriasis with approximately 40 percent body surface area involvement. for psoriasis, the patient was started on a biologic medication, with adalimumab (40 mg figure 1. multiple bullae overlying urticarial plaques on the patient’s abdomen. every 2 weeks) chosen due to the presence of mildly compromised renal function (creatinine of 1.1 mg/dl). the patient tolerated this treatment well. shortly after the patient’s third injection, widespread and morphologically distinct skin lesions erupted. physical examination revealed diffuse figure 2. urticarial plaque with overlying bullae on the patient’s right leg. skin march 2020 volume 4 issue 2 181 copyright 2020 the national society for cutaneous medicine erythematous urticarial plaques with overlying bullae (figures 1,2). laboratory findings were remarkable for eosinophilia, mild leukocytosis, and skin biopsy histology as well as direct immunofluorescence demonstrating features consistent with bullous pemphigoid. adalimumab was discontinued, and the patient was initiated on a prednisone taper along with adjunctive use of doxycycline 100mg twice daily and methotrexate 10mg weekly. although the patient was noted to have mild renal dysfunction, she had few affordable treatment options covered by her insurance that would address both psoriasis and bullous pemphigoid other than methotrexate. of note, creatinine remained stable while on methotrexate and did not elevate further than baseline level. improvement was noted with reductions in number and size of bullous and urticarial lesions in response to this treatment with no new bulla after 4 months and fully healed erosions off both doxycycline and prednisone which were tapered over a total of 6 months of use. despite reduction in the activity of bullous lesions, her psoriasis was noted to flare with an increase in affected body surface area to 25 percent. thus, secukinumab (150 mg every 2 weeks) was started in addition to methotrexate (max dose of 12.5mg weekly) as treatment for patient’s psoriasis which cleared after 2 months. bullous pemphigoid (bp) is an uncommon skin condition in which erythematous, urticarial papules and plaques progress to form tense bullae. typically noted in elderly patients, bullous pemphigoid is also the most common autoimmune bullous disease and is often associated with psoriasis.1 tnf-α is a cytokine that is involved in systemic inflammation and a large number of autoimmune diseases, including bp. the serum levels of tnf-α in bp are reported to be correlated with the severity and number of lesions in a given patient and anti tnf-α agents have been effectively used in the treatment of bp. paradoxically, there have also been reported cases of bp during treatment with anti-tnf-α therapy, as seen in our patient.2 however, in contrast to our patient, drug‐induced bullous pemphigoid is typically characterized by a younger age of onset.3 with many drug-induced dermatoses, there is usually uncertainty in the exact culprit agent. in this case, the temporal relationship with the onset and cessation of adalimumab is striking. for all patients presenting with bp, a thorough drug history should be taken. recognition of drug‐induced cases and prompt cessation of the offending agent may produce rapid improvement. as more cases of drug-induced bp are reported, we emphasize the need for further investigation into the incompletely understood effects of tnf-α antagonism on the immune system. conflict of interest disclosures: none funding: none corresponding author: aderonke obayomi, md mph tulane university school of medicine department of dermatology 1430 tulane avenue new orleans, la 70130 phone: 504-988-5114 fax: 504-988-7382 email: aobayomi@tulane.edu references: 1. schiavo a.l., ruocco e., brancaccio g. bullous pemphigoid: etiology, pathogenesis, and inducing factors: facts and controversies. clin dermatol. 2013;4:391–399. 2. altindag o., aydeniz a., gursoy s. a case with anti tnfα induced bullous pemphigoid. turk j rheumatol. 2010;25:214–216. 3. stavropoulos p.g., soura e., antoniou c. druginduced pemphigoid: a review of the literature. j eur acad dermatol venereol. 2014;9:1133– 1140. mailto:aobayomi@tulane.edu skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 852 skinmages high-grade undifferentiated pleomorphic sarcoma masquerading as acquired lymphangioma circumscriptum pooja h. rambhia, md1, sandra p. d’angelo, md2, pooja r. shah, md1 1 department of dermatology, donald and barbara zucker school of medicine at hofstra/northwell, new hyde park, ny 2 memorial sloan kettering cancer center, new york, ny a previously healthy woman in her 40s presented to the dermatology clinic with a 1year history of a tender, draining, enlarging mass on the left buttock. physical examination revealed an extensively indurated hyperpigmented nodule with numerous overlying clustered exophytic verrucous papules on the l medial buttock (see figure 1). initial skin biopsy of verrucous lesions was notable for lymphangioma with overlying condyloma, d2-40 positive. mri abdomen and pelvis with contrast demonstrated a left gluteal enhancing subcutaneous soft tissue mass, 10.3 x 8.2 x 8.8 cm in size, overlying and involving the left gluteus maximus, along with satellite nodules present in the medial gluteus maximus and paraspinal muscles, with bilateral pelvic and inguinal adenopathy. excisional deep tissue biopsy revealed a diagnosis of a high-grade, multifocal spindle and undifferentiated pleomorphic sarcoma. the patient subsequently underwent 4 cycles of neoadjuvant chemotherapy aim skin may 2023 volume 7 issue 3 (c) 2023 the authors. published by the national society for cutaneous medicine. 853 (doxorubicin, iphosphamide, mesna), followed by radical resection of the left gluteal region, with positive margins, followed by repeat surgical resection and reconstruction with left-sided latissimus dorsi myocutaneous free flap. the patient has now completed radiation therapy. soft tissue sarcoma is a heterogeneous group of rare malignancies of mesenchymal origin, that represents 0.8% of all adult cancers. prognostic factors associated with poor outcome include high histologic grade, large tumor size, presence of metastases, and unresectability1. herein, we report a novel case of high-grade soft-tissue undifferentiated pleomorphic sarcoma, masquerading as acquired lymphangioma circumscriptum (alc), as noted on initial skin biopsy of grouped flesh-colored verrucous papules overlying an indurated tender mass. alc is a lymphatic malformation occurring as sequela to any process which interrupts previously normal lymphatic drainage. as such, subcutaneous lymphatic cisterns are unable to drain completely into the general lymphatic system, resulting in lymphatic dilation and subsequent development of vesicular and papular lesions on the trunk, extremities, and anogenital areas.2 alc can mimic common infectious growths including molluscum contagiosum and condyloma accuminata, and accordingly be mismanaged. etiologic causes of alc including malignancy, and has previously been reported in the setting of cervical carcinoma, vulvar carcinoma, endometrial carcinoma, hodgkin lymphoma, rhabdomyosarcoma, rectal carcinoma, melanoma, and high-grade penile dysplasia2,3,4. other etiologic causes can include surgery, trauma, radiation therapy, chronic inflammatory conditions including hidradenitis suppurativa, and inflammatory bowel disease. to date, acquired lymphangioma circumscriptum has not been reported in the setting of underlying high-grade pleomorphic soft tissue sarcoma. as such, clinical presence of grouped frogspawn-like or verrucous papules, in an area of tender induration or lymphedema, should prompt a work-up to exclude an underlying malignant etiology as new onset alc may be masquerading an underlying malignancy. conflict of interest disclosures: none funding: none corresponding author: pooja r. shah md 1991 marcus ave., ste 300 new hyde park, ny 11042 e-mail: pshah12@northwell.edu references: 1. milgrom sa, million l, mandeville h, safwat a, ermoian rp, terezakis s. nonrhabdomyosarcoma soft-tissue sarcoma. pediatr blood cancer. 2021;68 suppl 2:e28279. doi:10.1002/pbc.28279 2. kreuter a, oellig f, kuntz t, et al. acquired lymphangioma circumscriptum in high-grade penile intraepithelial neoplasia. int j std aids. 2021;32(1):86-88. doi:10.1177/0956462420951094 3. luu yt, kimmis bd, bodine js, gloyeske nc, dai h. malignancy-associated acquired vulvar lymphangioma circumscriptum: a clinicopathologic study of 71 cases. j cutan pathol. 2022;49(5):426-433. doi:10.1111/cup.14181 4. chang mb, newman cc, davis md, lehman js. acquired lymphangiectasia (lymphangioma circumscriptum) of the vulva: clinicopathologic study of 11 patients from a single institution and 67 from the literature. int j dermatol. 2016;55(9):e482-e487. doi:10.1111/ijd.13264 microsoft word september 2020 scom 948 proof.docx skin september 2020 volume 4 issue 5 copyright 2020 the national society for cutaneous medicine 478 short communications autosensitization due to pediculosis capitis (a “pediculid”) in a 16-year old female: a case report logan j. kolb, do1, emma hignett, bs2, pearl kwong, md, phd1 1department of dermatology, hca healthcare/mercer university school of medicine/orange park medical center, orange park, fl 2university of central florida college of medicine, orlando, fl a 16-year-old indian female presented for a generalized, pruritic eruption of two weeks duration. hydrocortisone cream, oral antihistamines, and permethrin provided minimal relief. she denied recent travel or new medications. physical examination revealed generalized, excoriated erythematous papules and plaques with associated periorbital edema (figure 1 & 2). no mucosal changes or lymphadenopathy were noted. lesional and perilesional biopsies revealed a mixed perivascular lymphocyte-rich infiltrate with conspicuous eosinophils and negative direct immunofluorescence. labs revealed peripheral eosinophilia and negative celiac markers; therefore, a tentative diagnosis of hypersensitivity reaction was reached. the patient was started on prednisone 40mg daily, triamcinolone cream bid, and hydroxyzine 50 mg qhs. at one-week follow-up, the patient had minimal improvement and recalled having a slumber party with a contact with visible nits of her scalp. upon reexamination, numerous nits were observed on the hair shafts 1-4 cm from the scalp (figure 3). subsequently, the diagnosis of pediculosis capitis with an associated pediculid reaction was made. she was given two doses of oral ivermectin 10-days apart and a 3-week prednisone taper. the decision to treat with ivermectin was made because the patient refused to cut her hair and believed that current topical treatments were “toxic”. immediate family members were treated with topical ivermectin. pediculosis capitis is an infestation of the scalp by the head louse pediculous humanus capitis. the development of disseminated eczematous lesions as a result of the primary localized rash is known as an “id” reaction; commonly reported in association with stasis dermatitis, tinea, or scabies.1 autosensitization secondary to pediculosis capitis was first reported in 1946, and to our knowledge, this is just the fourth report of a pediculid case.2,3 histopathologic examination of id lesions shows acute spongiotic dermatitis with lymphocytic inflammation and eosinophils, as was seen in our patient.1 treatment of id reactions are twofold: suppressing inflammation with systemic corticosteroids, but most importantly, treating the underlying suspected source of hypersensitivity. in our case, the patient’s symptoms responded skin september 2020 volume 4 issue 5 copyright 2020 the national society for cutaneous medicine 479 minimally to prednisone until adequate antipediculosis treatment was instituted. figure 1. mildly erythematous, scaly papules coalescing on forehead, temple and cheek with periorbital edema. the prevalence of louse infections has increased over recent decades and is not limited to lower socioeconomic groups.4 interestingly, increased resistance to topical permethrin has been found in higher socioeconomic communities.4 the treatment of pediculosis capitis is often challenging due to increasing louse resistance, patient refusal to cut the affected hair, and increasing cost of treatment. there has been an emergence of lice removal centers that utilize machines to deliver intense heat to lice and nits; however, these treatments are costly to patients and are supported by small studies.5 there is also a trend towards refusal of topical treatment by patients due to fear of “chemicals” and preference towards treatments considered more natural (e.g. essential oils). modernday practices of taking “selfies” with friends and the taboos of disclosing personal infestation, which both played a role in acquiring the infestation in our patient, will pose challenges in decreasing the incidence. practitioners should be aware of these current trends, evolving treatments, and the presence of id reactions related to pediculosis. figure 2. numerous excoriation macules and papules of bilateral upper and lower extremities with sparing of the palms. skin september 2020 volume 4 issue 5 copyright 2020 the national society for cutaneous medicine 480 figure 3. numerous nits identified on scalp hair view under dermoscopy (inset: nit on hair shaft submerged in mineral oil, observed at 10x magnification) conflict of interest disclosures: none funding: this research was supported (in whole or in part) by hca and/or an hca affiliated entity. the views expressed in this publication represent those of the author(s) do not necessarily represent the official views of hca or any of its affiliated entities. corresponding author: logan kolb, do 210 9th st se rochester, mn 55904 507-292-7255 loganjkolb@gmail.com references: 1. refs ilkit m, durdu m, karakaş m. cutaneous id reactions: a comprehensive review of clinical manifestations, epidemiology, etiology, and management. crit rev microbiol. 2012;38(3): 191-202. 2. takci z, tekin ö, karadag as. a pediculid case: autosensitization dermatitis caused by pediculosis capitis. turkiye parazitol derg. 2012;36(3):185. 3. ronchese f. generalized dermatitis from pediculosis capitis. n engl j med. 1946;234(20), 665-666. 4. burgess if. human lice and their control. annu rev entomol. 2004;49. 5. bush se, rock an, jones sl, malenke jr, clayton dh. efficacy of the lousebuster, a new medical device for treating head lice (anoplura: pediculidae). j med entomol. 2014;48(1), 67-72. microsoft word september 2020 rescomp graham 930 proof.docx skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 424 resident competition research articles integrating electrical impedance spectroscopy into clinical decisions for pigmented skin lesions improves diagnostic accuracy: a multitiered study graham h. litchman, do, ms1, justin w. marson, md2, ryan m. svoboda, md, ms3, darrell s. rigel, md, ms4 1st. john’s episcopal hospital, new york, ny 2national society for cutaneous medicine, new york, ny 3penn state college of medicine, dermatology residency, hershey, pa 4new york university, grossmann school of medicine, new york, ny early recognition and treatment of melanoma positively impacts outcomes and healthcare costs.1-4 significant heterogeneity exists with clinicians’ ability to correctly assess the severity of pigmented lesions, leading to missed melanomas and unnecessary biopsies.5 the numberabstract introduction: the number-needed-to-biopsy (nnb) metric measures the efficiency of a clinician’s ability to accurately diagnose and recommend pigmented skin lesions (psls) for biopsy for suspected melanomas. electrical impedance spectroscopy (eis) is a non-invasive technique that measures differences in resistance between healthy and cancerous skin cells, intended as an aid to enhance diagnostic accuracy. methods: dermatology clinicians of three distinct groups (residents, physician assistants/nurse practitioners, and practicing dermatologists) were evaluated on their ability to accurately recommend suspect psls for biopsy before and after the integration of eis data. results: all three groups had a reduction in nnb after the inclusion of eis. instances of missed biopsies for malignant melanoma were significantly reduced with simultaneous significant reductions in unnecessary biopsies for benign lesions. there was a material improvement of biopsy selection for psls having clinically challenging features. eis also greatly improved the diagnostic acumen of clinicians whose assessments were less accurate than their peers prior to eis incorporation. conclusions: the integration of eis technology into the psl biopsy decision was demonstrated to be effective in significantly enhancing clinician nnb and more accurate psl biopsy selection. introduction skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 425 needed-to-biopsy (nnb) metric, expressed as a ratio between the total number of recommended biopsies divided by the number of biopsies for histologically confirmed malignant lesions, is typically used to assess biopsy efficiency.6,7 recent studies have suggested that dermatology clinicians of all levels could benefit from technology that augments clinical recognition of this tumor.1-4 electrical impedance spectroscopy (eis) is an fdaapproved technique in which the impedance (electrical resistance) of a pigmented skin lesion (psl) is measured by the application of an electric current is applied across it and the resistance spectrum is analyzed. this device returns a value on a 0 – 10 scale with a higher score associated with an increased risk of malignancy. psls scoring between 0 – 3 have a negative predictive value of 99% and those scoring 4-10 have a monotonically increasing risk of being malignant with a probability from 9-64%. to have the highest potential value in the practice setting, the greatest impact of diagnostic technologies should occur on clinically diagnostically challenging psls. the purpose of this study was to determine whether the integration of eis data into the biopsy decision led to a decrease in nnb, increased sensitivity, fewer unnecessary biopsies and fewer missed malignant biopsy decisions across all levels of training and whether the greatest impact occurred in the most clinically challenging psls. a data set of 43 randomly chosen clinically suspicious psls (27 benign, 16 malignant) from a previously published prospective blinded trial of 2,416 lesions where clinical images,8 clinical abcd criteria, and eis scores were evaluated. a survey using these lesions was provided to clinicians with three levels of training: practicing dermatologists (267 respondents; 11,481 decisions), residents (164 respondents; 7,052 decisions), and midlevels (physician assistants/nurse practitioners; 160 respondents; 6,880 decisions). lesion diagnoses were histologically confirmed, with benign lesions ranging from ordinary melanocytic nevi to mild or moderately dysplastic nevi. since eis has been shown to have some overlap with digital dermoscopy in psl evaluation, dermoscopic evaluation was specifically excluded to better measure the independent effect of eis on psl diagnosis.9 respondents were asked to provide a biopsy recommendation twice: based on clinical morphology alone, and then again after the eis device (nevisense; scibase ab, stockholm, sweden) score was provided. significance was calculated using mcnemar’s and differences of proportions testing. sensitivity and specificity for all clinician levels before and after eis incorporation were also calculated. reductions in nnb were observed across all three clinician levels (table 1) after incorporating eis technology into their biopsy decisions, with decreases of 14.8%, 16.8%, and 16.0% for residents, midlevels, and practicing dermatologists, respectively. the number of unnecessary biopsies for benign lesions significantly decreased, with a corresponding significant increase in the number of biopsies for malignant psls (figure 1). when grouped into quartiles based on percentages of correct assessments, groups with the lowest preeis correct evaluations experienced the methods results skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 426 table 1. number-needed-to-biopsy values and psl biopsy selection sensitivity and specificity before and after incorporation of eis technology (ranges in parentheses represent 95% confidence intervals) for residents, midlevels, and practicing dermatologists before and after incorporation of eis technology. level of training % sensitivity pre-eis (95% ci) % sensitivity post-eis (95% ci) % specificity pre-eis (95% ci) % specificity post-eis (95% ci) nnb preeis nnb posteis % reduction in nnb post-eis number of decisions (n)* missed melanomas pre-eis (%)* missed melanomas post-eis (%)* resident 79.5 (77.9 – 81.1) 94.9 (94.0 – 95.7) 49.8 (48.3 – 51.3) 57.3 (55.9 – 58.8) 5.6 4.7 14.8 n = 1312 93 (7.09%) 13 (0.99%) midlevel 84.1 (82.7 – 85.5) 97.8 (97.2 – 98.3) 34.8 (33.4 – 36.3) 46.7 (45.2 – 48.2) 6.2 5.2 16.8 n = 1280 80 (6.25%) 7 (0.55%) practicing dermatologist 84.4 (83.2 – 85.4) 98.0 (97.5 – 98.4) 33.6 (32.5 – 34.7) 44.5 (43.3 – 45.6) 6.3 5.3 16.0 n = 2136 153 (7.16%) 12 (0.56%) * refers to melanomas with eis score of 7+ (total of 8 lesions) figure 1. changes in number of biopsy decisions figure 2. % correct assessment at all levels of training skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 427 table 2. number of melanomas that would be missed and benign biopsies that would be performed both clinically and with the addition of electrical impedance spectroscopy results by a sample of 591 dermatology clinicians (164 residents, 160 nurse practitioners/physician assistants, and 267 practicing dermatologists) assessing 43 pigmented lesions. with the availability of eis data for the biopsy decision, 1334 more melanomas were chosen for biopsy and 1630 benign psls had biopsies avoided. practicing dermatologists residents midlevels combined eis score clinical abcd features present melanomas identified for biopsy without eis, n (%) melanomas identified for biopsy with addition of eis, n (%) melanomas identified for biopsy without eis, n (%) melanomas identified for biopsy with addition of eis, n (%) melanomas identified for biopsy without eis, n (%) melanomas identified for biopsy with addition of eis, n (%) melanomas identified for biopsy without eis, n (%) melanomas identified for biopsy with addition of eis, n (%) net change in number of melanomas biopsied with addition of eis (n) p-valuea net changes in decision to biopsy 9 abcd 237 (88.8) 265 (99.3) 142 (85.6) 163 (99.4) 141 (88.1) 160 (100) 520 (88.0) 588 (99.5) 68 < 0.001 +376* 8 abcd 267 (100) 267 (100) 163 (99.4) 163 (99.4) 156 (97.5) 159 (99.4) 586 (99.2) 589 (99.7) 3 0.180 7 abcd 259 (97.0) 266 (99.6) 153 (93.3) 162 (98.8) 154 (96.3) 159 (99.4) 566 (95.8) 587 (99.3) 21 < 0.001 9 abcd 266 (99.6) 267 (100) 163 (99.4) 162 (98.8) 160 (100) 160 (100) 589 (99.7) 589 (99.7) 0 1 7 abc 263 (98.5) 267 (100) 162 (98.8) 164 (100) 160 (100) 160 (100) 585 (99.0) 591 (100) 6 0.014 8 abc 237 (88.8) 265 (99.3) 145 (88.4) 161 (98.2) 141 (88.1) 160 (100) 523 88.5) 586 (99.2) 63 < 0.001 4 abc 266 (99.6) 264 (98.9) 161 (98.2) 158 (96.3) 159 (99.4) 156 (97.5) 586 (99.2) 578 (97.8) -8 0.033 5 abc 214 (80.1) 258 (96.6) 127 (77.4) 148 (90.2) 133 (83.1) 158 (98.8) 474 (80.2) 564 (95.4) 90 < 0.001 10 abc 252 (94.4) 264 (98.9) 155 (94.5) 162 (98.8) 153 (95.6) 157 (98.1) 560 (94.8) 583 (98.6) 23 < 0.001 8 bcd 202 (75.7) 263 (98.5) 136 (82.9) 162 (98.8) 135 (84.4) 158 (98.8) 473 (80.0) 583 (98.6) 110 < 0.001 6 ab 163 (61.0) 263 (98.5) 93 (56.7) 156 (95.1) 93 (58.1) 158 (98.8) 349 (59.0) 577 (97.6) 228 < 0.001 +958* 4 ab 209 (78.3) 238 (89.1) 111 (67.7) 131 (79.9) 118 (73.8) 138 (86.3) 438 (74.1) 507 (85.8) 69 < 0.001 6 ac 113 (42.3) 254 (95.1) 55 (33.5) 141 (86.0) 71 (44.4) 152 (95.0) 239 (40.4) 547 (92.6) 308 < 0.001 6 cd 214 (80.1) 262 (98.1) 116 (70.7) 155 (94.5) 118 (73.8) 155 (96.9) 448 (75.8) 572 (96.8) 124 < 0.001 6 cd 193 (72.3) 263 (98.5) 89 (54.3) 149 (90.9) 116 (72.5) 158 (98.8) 398 (67.3) 570 (96.4) 172 < 0.001 6 c 249 (93.3) 259 (97.0) 116 (70.7) 153 (93.3) 146 (91.3) 156 (97.5) 511 (86.5) 568 (96.1) 57 < 0.001 total 3604 4185 2087 2490 2154 2504 7845 9179 1334 < 0.001 skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 428 eis score clinical abcd features present benign biopsies without eis, n (%) benign biopsies with eis, n (%) benign biopsies without eis, n (%) benign biopsies with eis, n (%) benign biopsies without eis, n (%) benign biopsies with eis, n (%) benign biopsies without eis, n (%) benign biopsies with eis, n (%) net change benign biopsies with eis (n) p-valuea net change in decision to biopsy 2 abcd 215 (80.5) 77 (28.8) 81 (49.4) 14 (8.5) 123 (76.9) 45 (28.1) 419 (70.9) 136 (23.0) -283 < 0.001 -1368* 5 abcd 259 (97.0) 267 (100) 150 (91.5) 161 (98.2) 160 (100) 159 (99.4) 569 (96.3) 587 (99.3) 18 < 0.001 0 abcd 263 (98.5) 177 (66.3) 158 (96.3) 102 (62.2) 160 (100) 100 (62.5) 581 (98.3) 379 (64.1) -202 < 0.001 1 acd 223 (83.5) 91 (34.1) 122 (74.4) 40 (24.4) 135 (84.4) 0 (0) 480 (81.2) 131 (22.2) -349 < 0.001 2 acd 235 (88.0) 131 (49.1) 138 (84.1) 61 (37.2) 147 (91.9) 78 (48.8) 520 (88.0) 270 (45.7) -250 < 0.001 4 abd 261 (97.8) 264 (98.9) 150 (91.5) 151 (92.1) 158 (98.8) 156 (97.5) 569 96.3) 571 (96.6) 2 0.617 6 abc 185 (69.3) 261 (97.8) 85 (51.8) 149 (90.9) 116 (72.5) 159 (99.4) 386 (65.3) 569 (96.3) 183 < 0.001 4 abc 241 (90.3) 249 (93.3) 128 (78.0) 131 (79.9) 143 (89.4) 148 (92.5) 512 (86.6) 528 (89.3) 16 0.042 1 abc 237 (88.8) 110 (41.2) 125 (76.2) 46 (28.0) 142 (88.8) 63 (39.4) 504 85.3) 219 (37.1) -285 < 0.001 2 acd 147 (55.1) 40 (15.0) 95 (57.9) 17 (10.4) 97 (60.6) 22 (13.8) 339 (57.4) 79 (13.4) -260 < 0.001 4 bcd 213 (79.8) 234 (87.6) 119 (72.6) 124 (75.6) 131 (81.9) 147 (91.9) 463 (78.3 505 (85.4) 42 < 0.001 4 ab 157 (58.8) 220 (82.4) 97 (59.1) 116 (70.7) 108 (67.5) 130 (81.3) 362 (61.3) 466 (78.8) 104 < 0.001 -262* 6 ac 194 (72.7) 256 (95.9) 46 (28.0) 142 (86.6) 109 (68.1) 156 (97.5) 349 (59.1) 554 93.7) 205 < 0.001 2 ac 141 (52.8) 45 (16.9) 39 (23.8) 6 (3.7) 78 (48.8) 23 (14.4) 258 (43.7 74 (12.5) -184 < 0.001 1 ac 161 (60.3) 41 (15.4) 55 (33.5) 10 (6.1) 90 (56.3) 15 (9.4) 306 (51.8) 66 (11.1) -240 < 0.001 0 ac 142 (53.2) 29 (10.9) 35 (21.3) 2 (1.2) 81 (50.6) 19 (11.9) 258 (43.7) 50 (8.5) -208 < 0.001 5 ac 161 (60.3) 261 (97.8) 83 (50.6) 135 (82.3) 91 (56.9) 155 (96.9) 335 (56.7) 551 (93.2) 216 < 0.001 4 bc 218 (81.6) 245 (91.8) 108 (65.9) 120 (73.2) 131 (81.9) 142 (88.8) 457 (77.3) 507 (85.8) 50 < 0.001 1 bc 155 (58.1) 34 (12.7) 51 (31.1) 10 (6.1) 0 (0) 26 (16.3) 206 (34.9) 70 (11.8) -136 < 0.001 4 cd 61 (22.8) 210 (78.7) 53 (32.3) 102 (62.2) 61 (38.1) 128 (80.0) 175 (29.6) 440 (74.5) 265 < 0.001 3 cd 174 (65.2) 103 (38.6) 67 (40.9) 22 (13.4) 102 (63.8) 46 (28.9) 343 (58.0) 171 (28.9) -172 < 0.001 4 cd 96 (36.0) 204 (76.4) 32 19.5) 75 (45.7) 61 (38.1) 129 (80.6) 189 (32.0) 408 (69.0) 219 < 0.001 2 a 150 (56.2) 43 (16.1) 65 (39.6) 10 (6.1) 88 (55.0) 20 (12.5) 303 (51.3) 73 (12.4) -230 < 0.001 1 c 55 (20.6) 24 (9.0) 2 (1.2) 1 (0.6) 33 (20.6) 3 (1.9) 90 15.2) 28 (4.7) -62 < 0.001 5 c 131 (49.1) 238 (89.1) 29 17.7) 111 (67.7) 77 (48.1) 143 (89.4) 237 (40.1) 492 (83.2) 255 < 0.001 2 c 191 (71.5) 74 (27.7) 76 (46.3) 22 (13.4) 114 (71.3) 50 (31.3) 381 (64.5) 146 (24.7) -235 < 0.001 3 c 120 (44.9) 76 (28.5) 34 (20.7) 9 (5.5) 78 (48.8) 38 (23.8) 232 (39.3) 123 (20.8) -109 < 0.001 total 4,847 4,004 2223 1889 2814 2300 9823 8193 -1630 < 0.001 amcnemar’s test *p<0.001 eis = electrical impedance spectroscopy, % = percent, a = asymmetry, b = border irregularity , c= color variegation, d = diameter ≥ 6m skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 429 greatest improvement (figure 2), more closely approximating the correct percentage biopsy-decision levels of their diagnostically superior colleagues. overall sensitivity and specificity for all clinicians improved by 14% and 10.2%, respectively. the sensitivities and specificities for each level of training also significantly improved (table 1). when evaluating melanomas with eis scores of 7 or higher, the probability of correctly identifying melanomas across all levels of training significantly increased from 93.1% with clinical evaluation alone to more than 99.3% when eis was integrated into the biopsy decision (p<0.00001) (table 1). in the composite training level analysis, eis technology contributed to 1,343 fewer missed melanomas, and 1,613 unnecessary benign biopsies were avoided. eis score integration had the greatest impact noted on the more clinically challenging psls for all 3 groups (table 2). there was a significantly greater increase in psls selected for biopsy post-integration of eis data for the melanomas that had fewer (1-2) clinical abcd criteria and a similar significantly greater decrease for those benign psls with the greatest number (3-4) abcd criteria clinically noted. recent technological advances in psl diagnosis have aimed at improving accuracy and efficiency. in order to have their greatest potential positive influence, the greatest impact should be on lesions that are clinically equivocal. these findings suggest that integrating eis into the biopsy decision, beyond the overall improvement in psl selection for biopsy, has a materially positive effect on the more clinically challenging lesions. the smaller nnb noted in the study for all levels of training suggests that eis data made the biopsy selection more efficient. the reductions in nnb led to a decrease in unnecessary biopsies of benign lesions, and a simultaneous increase in biopsies recommended for malignant psls (figure 1). the percent reduction and values of nnb post-eis data integration demonstrates the benefits that eis provides beyond baseline diagnostic skill. this finding is further strengthened by the lowest-scoring study participants demonstrating the greatest improvements in percentage of correct assessments, narrowing the relative gaps in diagnostic acumen compared to their more diagnostically astute peers. a malignant melanoma that is missed during initial consultation will also lead to an increase in downstream diagnosis and treatment costs, as well as less favourable patient outcomes.3 when evaluating the eight psls that were histologically proven to be malignant and had eis scores of 7+, the fact that almost none of these melanomas (0.7%) escaped biopsy reinforces the inference that integration of eis information into the biopsy decision could materially lower the economic and social costs associated with missed melanomas. a limitation of this study is that decisions were made based on clinical images alone versus in vivo examination. dermoscopic images were also not included to remove any possible confounding effects of dermoscopy, allowing for assessment of the independent impact of eis technology. in addition, despite its growing use as a biopsy efficacy metric, nnb may not be ideal due to a lack of standardization and underreporting. for these reasons, a lower nnb may not necessarily lead to more efficient outcomes.10 discussion skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 430 our study demonstrated the benefits of incorporating eis technology beyond clinical psl diagnosis alone for biopsy selection across all levels of training, as measured by decreases in nnb, increased sensitivity and specificity, fewer unnecessary biopsies of benign lesions, and more importantly, almost the complete elimination of missed higher probability malignant melanomas in our study series. greater homogeneity in diagnostic acumen was achieved, thus increasing the overall efficacy in correct psl assessments. the fact that a material positive impact on psl biopsy selection occurred in the most clinically-challenging lesions suggests that this technology may be particularly helpful in this spectrum of psls. in an era of healthcare economics and better evaluation of social costs, maximizing efficiency in melanoma detection is paramount in order to address the steadily rising rates of this cancer. conflict of interest disclosures: dr. litchman and dr. svoboda are dermatology residents and have no relevant disclosures or conflicts of interest. dr. marson is a melanoma clinical research fellow and has no relevant disclosures or conflicts of interest. darrell s rigel is a clinical professor of dermatology at nyu and has served as consultant for scibase ab. funding: this study was partly funded by a grant from scibase ab. corresponding author: graham h litchman, do, ms 35 e 35th st. #208 new york, ny 10016 email: graham.litchman@gmail.com references: 1. svoboda rm, prado g, mirsky rs, rigel ds. assessment of clinician accuracy for diagnosing melanoma on the basis of electrical impedance spectroscopy score plus morphology versus lesion morphology alone. j am acad dermatol. 2019;80(1):285-287. 2. u.s. cancer statistics working group. u.s. department of health and human services, centers for disease control and prevention, national cancer institute, nov. 2018, www.cdc.gov/cancer/dataviz. 3. guy gp jr, ekwueme du, tangka fk, richardson lc. melanoma treatment costs: a systematic review of the literature, 1990-2011. american journal of preventative medicine. 2012;43(5):537-545. doi: 10.1016/j.amepre.2012.07.031. 4. arnold jd, yoon s, kirkorian ay. the national burden of inpatient dermatology in adults. journal of the american academy of dermatology. 2019;80(2):425432. 5. anderson am, matsumoto m, saul mi, secrest am, ferris lk. accuracy of skin cancer diagnosis by physician assistants compared with dermatologists in a large health care system [published correction appears in jama dermatol. 2018 jun 1;154(6):739]. jama dermatol. 2018;154(5):569-573. doi:10.1001/jamadermatol.2018.0212 6. krensel m, schäfer i, augustin m. cost-of-illness of melanoma in europe – a systematic review of the published literature. journal of the european academy of dermatology and venereology. 2019;33(3):504-510. 7. privalle a, havighurst t, kim k, bennett dd, xu yg. number of skin biopsies needed per malignancy: comparing the use of skin biopsies among dermatologists and nondermatologist clinicians. journal of the american academy of dermatology. 2020;81(1):110-116. 8. malvehy j, hauschild a, curiel-lewandrowski c, et al. clinical performance of the nevisense system in cutaneous melanoma detection: an international, multicentre, prospective and blinded clinical trial on efficacy and safety. the british journal of dermatology. 2014;171(5):1099-1107. 9. rocha l, menzies sw, lo s, et al.analysis of an electrical impedance spectroscopy system in shortterm digital dermoscopy imaging of melanocytic lesions. the british journal of dermatology. 2017;177(5):1432-1438. 10. ferris lk, rigel ds, siegel dm, skelsey mk, et al. impact on clinical practice of a non-invasive gene expression melanoma rule-out test: 12-month followup of negative test results and utility data from a large us registry study. dermatology online journal. 2019;25(5). pii: 13030/qt61w6h7mn. conclusion z draelos,1 l kircik,2 d rigel3 1dermatology consulting services, pllc, high point, nc; 2icahn school of medicine at mount sinai, new york, ny, and indiana medical center, indianapolis, in; 3new york university medical center, new york, ny introduction conclusions references objective methods the low prevalence of allergic contact dermatitis using a petrolatum ointment containing lanolin alcohol u lanolin alcohol (la) is an ingredient used in wound healing ointments for its high cholesterol content, a key component of intercellular lipids1 u la reduces transepidermal water loss (tewl), and has been shown to have anti-inflammatory, skin-protecting, and barrier repair properties1 u la is a subfraction of lanolin (wool wax), a natural product derived from the sebaceous glands of sheep u the purification process of la can vary, leading to many different purities of la being available in the marketplace, and reports of allergic contact dermatitis (acd) have raised concerns for its use u standard dermatology patch testing uses a specific la preparation (amerchol l101®, available as 10% in mineral oil) that has been shown to result in higher rates of allergy in patch testing than other sources of la2–4 u in 2011, the concentration of amerchol l101 in patch testing was increased from 30% in petrolatum (final 3% la) to 50% (final 5% la), resulting in an increase in reported la allergy rates (figure 1)5,6 results u 499 subjects were enrolled and completed the study u no subjects were excluded during screening for lanolin-related allergies u each subject had one lesion removed; procedures included shave biopsies, shave excisions, punch biopsies, and excisions u the incidence of erythema and itch was very low, with only mild scores being recorded; no incidence of pain was reported (figure 2, table 1) u no acd was observed, and consequently no patch testing was conducted (figure 3, table 2) u there were no signs of infection in any subject u 0.5% of subjects experienced an adhesive reaction u no incidence of acd was observed in 499 subjects u the absence of acd with spo in clinical studies may be due to its formulation containing a proprietary highly purified la, and not the la used in the standard dermatology patch test tray u these data support the observation that la preparations can differ in allergenicity based on the quality of their purification u spo has been clinically demonstrated to be well tolerated and safe for use in postsurgical wound care 1. hoppe u, et al. the lanolin book. hamburg: clausen & bosse, 1999 2. knijp j, et al. contact dermatitis. 2019; 80:298–303 3. uter w, et al. contact dermatitis. 2018;78:355–371 4. meist ryn, et al. dermatitis. 2013;24:119–123 5. warshaw e, et al. dermatitis. 2009;20:79–88 6. dekoven j, et al. dermatitis. 2016;28:33–46 7. draelos z, et al. j am acad dermatol. 2011;64:s23–s29 8. taylor sc, et al. j am acad dermatol. 2011;64:s30–s35 9. sarnoff ds. j am acad dermatol. 2011;64:s36–s43 10. trookman n, et al. j am acad dermatol. 2011;64:s16–s22 u to evaluate the tolerability and safety of an otc la-containing spo used for postsurgical skin care subjects u male and female subjects age 18–75 years u subjects had a lesion located on the face, neck, trunk, arms, or legs that required surgical removal u subjects with lanolin-related allergies were excluded sponsorship: research sponsored by beiersdorf inc., wilton, ct u in previous clinical trials and patch testing, an otc lacontaining skin protectant ointment (spo; aquaphor healing ointment, beiersdorf inc., usa) has demonstrated efficacy in accelerating wound healing with no incidence of acd7–10 u spo contains a highly purified la from a different manufacturer than that used in the standard patch test series u this study specifically tested the incidence of acd with spo in a clinical setting assessments u wound sites were evaluated 10–14 days after surgery for: – erythema, itching, and pain (0 = none, 1 = mild, 2 = moderate, 3 = marked, and 4 = severe) – signs of infection (purulent discharge) – acd (erythema, edema, papules, vesicles, bullae, weeping) u if acd was suspected, the subject was photographed and patch tested with the product and individual ingredients at a naïve site under occlusive patch conditions and evaluated on the following scale 1 hour after removal: 0 = none/absent; +/= equivocal, + = weak, ++ = strong, +++ = severe 2.4 0 1 2 3 4 5 6 p o si ti ve p a tc h t e st ( % ) 1998 2000 2002 2004 2006 2008 2010 2012 2014 2016 50% 30% amerchol l101 50% becomes standard la for patch testing 2.2 2.22.3 2.2 2.5 4.6 5.4 1.8 1.8 2.1 2.1 5.8% 1.0% 0% 0 1 2 3 4 5 6 7 erythema (score=1) itching (score=1) pain 0.06 0.01 0 0 0.02 0.04 0.06 0.08 0.1 erythema itching pain fr e q u e n cy ( % ) n=499 incidence score m e a n s co re n 29 5 figure 1. north american contact dermatitis group lanolin alcohol (la) testing results, 1998–20165,6 figure 2. incidence and scores for erythema, itching, and pain (n=499) apply skin protectant ointment to wound 1–3×/day (10–14 days) wound assessment in-of�ce surgical removal of lesion 0 2 0 0 0 1 2 3 4 5 acd adhesive reaction purulent discharge infection fr e q u e n cy ( n ) figure 3. tolerability results (n=499) acd, allergic contact dermatitis table 1. descriptive statistics for incidence of erythema, itching, and pain (0 to 4 severity scale; n=499) erythema itching pain mean score 0.060 0.010 0.000 standard deviation 0.246 0.100 0.000 severity score, n (%) 0 470 (94.2) 494 (99.0) 499 (100) 1 29 (5.8) 5 (1.0) 0 (0) 2 0 (0) 0 (0) 0 (0) 3 0 (0) 0 (0) 0 (0) 4 0 (0) 0 (0) 0 (0) table 2. descriptive statistics for presence of acd, adhesive reactions, purulent discharge, and suspicion of infection (n=499) suspicion of acd adhesive reaction* purulent discharge infection suspected mean score 0.000 0.005 0.000 0.000 standard deviation 0.000 0.071 0.000 0.000 frequency, n (%) no 499 (100) 398 (99.5) 499 (100) 499 (100) yes 0 (0) 2 (0.5) 0 (0) 0 (0) *was not evaluated in 99 patients study design u three-center, open-label study u subjects underwent a surgical procedure to remove lesion appropriate for healing by secondary intention u each subject had one lesion surgically removed by shave removal using a blade, or by excision with a scalpel. no sutured wounds were allowed u subjects were instructed to clean the wound daily with a mild cleanser and apply spo one to three times per day for 10–14 days u after spo application, wounds were covered with latex-free adhesive bandages or dressing deemed appropriate by the investigator u bandages were used each day for 7 days or as instructed by the physician microsoft word july 2020 rlet 861 proof returned.docx skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 331 research letters the impact of psoriasis on the quality of life of patients in san antonio, tx anisha guda, bs1, catherine kowalewski, md2, sandra osswald, md2, richard usatine, md2 1ut health san antonio, long school of medicine, san antonio, tx 2department of dermatology, ut health san antonio, san antonio, tx to the editor: psoriasis impacts 2%1 of the world’s population, including both men and women. the disease significantly affects the quality of life of patients by causing loss of self-confidence, anxiety, anger, and depression.2 it also results in occupational and sexual dysfunction and impairment of psychosocial factors. the chronicity of the disease, lack of control, and feeling of hopelessness all contribute to the negative impact of the disease on patients.3 there is very little information available regarding the impact of psoriasis on the lives of patients living in san antonio, tx. additionally, the effect of the disease on the homeless population in this community hasn’t been studied. in order to address this problem, an institutional review board (irb) approved, abstract background: psoriasis impacts 2% of the world’s population. the disease affects the quality of life of patients by causing pain and depression. little information is available regarding the impact of psoriasis on san antonio patients. objective: this project obtained information from patients about how they are coping with psoriasis, impact on their quality of life, barriers to care, and support systems they have. methods: an irb approved six question survey was administered to 50 patients who attended the va, a psoriasis support group, and haven for hope homeless clinic. results: 40% of patients who completed the survey had been living with psoriasis for less than 5 years. 75% of patients in this group claimed they were severely depressed. the disease impacted them most psychologically and their greatest barrier to care was access to medications that “cured” their psoriasis. 60% of the patients were living with psoriasis for more than 5 years, and 81% claimed they were not depressed at all. psoriasis impacted them most financially and their greatest barrier was the cost of care. conclusion: acutely, psoriasis patients are impacted psychologically and are frustrated with their disease. over time, they learn to live with their condition and are impacted by the economic aspects of care. skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 332 six-question survey was administered to 50 patients who attended the veteran’s affairs (va) dermatology clinic (surveyed over the phone), psoriasis support group (surveyed in person), and haven for hope homeless clinic (provides dermatologic services to the uninsured and underinsured (surveyed in person)). there was a 100% response rate. the survey questions assessed how long patients had been living with psoriasis, their mood, how significantly psoriasis has impacted their life, what barriers to care they faced, and what type of support systems are available. the age range of participants was 39-72. the median age of participants was 54 and the iqr was 22. twenty-six male patients and twenty-four female patients participated. forty percent of patients who completed the survey reported a duration of disease less than 5 years. of those, seventy-five percent claimed that they were severely depressed (table 1). the disease impacted them the most psychologically and their greatest barrier to care was access to effective medications that “cured” their psoriasis. sixty percent of patients who completed the survey reported a duration of disease between 5-10 years. of those, eighty-three percent claimed they were not depressed at all. psoriasis impacted them most financially with the greatest barrier being cost of care. patients at the va dermatology clinic were impacted the most psychologically by the disease, rated social stigma and access to social support as their greatest barriers to care, and mentioned that their family was their greatest source of support. there were significantly higher rates of moderate to severe depression in this group compared to the other populations (p<0.05). patients at the haven for hope clinic were impacted the most physically and psychologically by the disease, rated the cost of care and transportation as their greatest barriers to care, and the dermatologist as their greatest source of support. patients in the psoriasis support group were impacted the most socially by the disease, rated knowledge about the disease as their greatest barrier to care, and mentioned that the support group was their greatest source of support (table 2, figure 1). patients in the support group were happier overall. they significantly rated lower levels on the scale for the impact of the disease on their life (p<0.03). psoriasis has greatly impacted the quality of life of patients in san antonio, tx. based on the survey data collected, more patients with a shorter duration of psoriasis report severe depression. this may be because patients with recently diagnosed psoriasis are overwhelmed by their disease and do not yet know how to manage it. providing emotional support early in the disease from a dermatologist, family and friends, and local support groups may help patients better cope with their feelings. additionally, the study demonstrated that individual population groups are affected in different ways by psoriasis. patients at the va report social barriers, haven for hope patients report economic barriers, and members of the support group report educational barriers. it is important to note the needs of these patient groups so that the most optimal care can be provided to them. going forward, interventions to address these needs including promoting social acceptance in the community, providing financial assistance to the uninsured, and educating the public about psoriasis will help improve overall care. many studies have been completed in the past in other regions of the united states regarding the impact of psoriasis on the quality of life of patients. one notable study was conducted in 1998 by the national psoriasis foundation4. they reported that skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 333 79% of patients mentioned that the disease had a negative impact on their life. particularly, the condition affected them emotionally and patients felt embarrassed when people viewed their psoriasis. they also stated that socially there were various misconceptions about the disease leading to social stigma. another study was completed in 19975 to determine the economic impact of psoriasis and its association with psoriasis severity. they found that patients with more severe psoriasis have higher expenses. as a result, patients with severe psoriasis have a lower quality of life due to the financial implications associated with the disease. a study was completed in 20026 that determined the health effects of psoriasis on patients. they found that psoriasis patients had a lower levels of self-confidence and experienced difficulties with social functioning compared to individuals without chronic disease. additionally, a study was completed in 20047 that described certain characteristics that impact the quality of life of psoriasis patients. they found that patients with extensive skin involvement had a lower quality of life compared to other patients. additionally, young patients and female patients had significant reductions in their quality of life. in 2015,8 a study was completed to determine the impact of disease burden on the quality of life of psoriasis patients. they found that patients with severe psoriasis have lower levels of quality of life and overall health. although many years have passed since the studies described, it is interesting to see that patients are continuing to face similar issues with their condition. psoriasis is a condition that affects patients on multiple levelsnot just physically, but also emotionally, socially, and financially. our study is unique because we were able to compare the impact of psoriasis amongst various population groupsveteran patients, the homeless population, and psoriasis support group members. we were able to identify the barriers to care and sources of support associated with these groups. additionally, we were able to determine that patients with a shorter duration of psoriasis have more severe forms of depression compared to patients with a longer duration of psoriasis. this finding has not been reported in other studies before and would be interesting to explore further. previous studies have reported that more severe forms of psoriasis are correlated with lower levels of quality of life. although our study did not stratify patients according to their level of psoriasis, this would be interesting to study in the future. the qualitative and quantitative data that we have collected will be important to keep in mind when caring for patients in san antonio, tx but also in other communities in the country. table 1. the effect of psoriasis duration on the mood of patients table 2. the impact of psoriasis on different population groups va dermatology clinic haven for hope homeless clinic psoriasis support group greatest impact psychological physical and psychological social stigma barriers to care social stigma cost of care and transportation knowledge/ understanding of disease sources of support family dermatologist support group psoriasis duration depression status none (n=26) mild (n =3) moderate (n=4) severe (n =17) <5 years 1 2 2 15 5-10 years 25 1 2 2 skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 334 figure 1. barriers to care for psoriasis patients at the va figure 2. barriers to care for psoriasis patients at haven for hope clinic conflict of interest disclosures: none funding: none corresponding author: anisha guda, bs ut health san antonio long school of medicine san antonio, tx 78229 email: gudav@livemail.uthscsa.edu references: 1. sarkar r, chugh s, and bansal s. general measures and quality of life issues in psoriasis. indian dermatol online j. 2016;7(6):481-488. 2. studzinska m, ziemecki p, ziemecka a, and paryka i. the psychological and social support in patients with psoriasis. pol merkur lekarski. 2013;35(207):171-174. 3. hawro t, miniszewska j, chodkiewicz j, et al. anxiety, depression and social support in patients with psoriasis. prezgl lek. 2007;64(9):568-571. 4. krueger g, koo j, lebwohl m, et al. the impact of psoriasis on quality of life: results of a 1998 national psoriasis foundation patientmembership survey. arch dermatol.2001;137:280-284. 5. feldman sr, fleischer ab, reboussin dm, et al. the economic impact of psoriasis increases with psoriasis severity. jaad.1997;37(4):564-569. 6. weiss sc, kimball ab, liewehr dj, et al. quantifying the harmful effect of psoriasis on health related quality of life. jaad. 2002;47(4):512-518. 7. gelfand jm, feldman sr, stern rs, thomas j, rolstad t, and margolis dj. determinants of quality of life in patients with psoriasis: a study from the us population. jaad. 2004;51(5):704708. 8. edson he, zhu b, guo j, maeda ct, and lebwohl m. disease burden and quality of life in psoriasis patients with and without comorbid psoriatic arthritis: results from national psoriasis foundation panel surveys. cutis. 2015;95(3):173178. dupilumab with concomitant topical corticosteroids in atopic dermatitis patients who are inadequately controlled with or medically inadvisable for cyclosporine a: a phase 3 clinical trial (liberty ad café) presented at the 2017 fall clinical dermatology conference; las vegas, nv, usa; october 12-15, 2017. marjolein de bruin-weller1, diamant thaçi2, catherine smith3, allen radin4, rick zhang5, bolanle akinlade4, abhijit gadkari4, laurent eckert6, thomas hultsch7, gianluca pirozzi8, neil mh graham4, brad shumel4 1university medical center utrecht, utrecht, netherlands; 2university of lübeck, lübeck, germany; 3st. john’s institute of dermatology, london, uk; 4regeneron pharmaceuticals, inc., tarrytown, ny, usa; 5regeneron pharmaceuticals, inc., basking ridge, nj, usa; 6sanofi, chilly-mazarin, france; 7sanofi, cambridge, ma, usa; 8sanofi, bridgewater, nj, usa b a c k g r o u n d 1 α o b j e c t i v e c o n c l u s i o n s – – m e t h o d s study design patient eligibility – � � � � � safety table 1. baseline characteristics. – – – – – – – – � � � outcomes – – – – – r e s u lt s patient disposition and baseline characteristics efficacy p – placebo sc qw+tcsb (n = 108) dupilumab 300 mg sc qw+tcsb (n = 110) post-treatment options open-label extension safety follow-up through week 28 screening (2 weeks) and tcs standardization (2 weeks) dupilumab 300 mg sc q2w+tcsb (n = 107) treatment period (16 weeks) follow-up period (12 weeks) loading dose (day 1a) day –28 to day –1 baseline week 28week 16 r figure 1. study design. 0 10 20 30 40 50 60 70 80 90 100 0 2 4 6 8 10 12 14 16 p ro p o rt io n o f p a ti e n ts a c h ie vi n g e a s i75 f ro m b a se lin e ( % ) weeks overall population (primary endpoint) 29.6 62.6* 59.1* *p < 0.0001 0 10 20 30 40 50 60 70 80 90 100 0 2 4 6 8 10 12 14 16 weeks patients with prior csa usea placebo+tcs dupilumab 300 mg q2w+tcs *p = 0.0001 †p = 0.0002 26.4 58.0* 56.5† (a) (b) dupilumab 300 mg qw+tcs figure 2. proportion of patients of the overall study population (a) and patients with prior csa use (b) achieving easi-75 at week 16 (primary endpoint). 0 10 20 30 40 50 60 70 80 90 100 0 2 4 6 8 10 12 14 16 p ro p o rt io n o f p a ti e n ts w it h ≥ 4 -p o in t im p ro ve m e n t i d l q i fr o m b a se lin e ( % ) weeks poem (mcid ≥ 4) dlqi (mcid ≥ 4) 0 10 20 30 40 50 60 70 80 90 100 0 2 4 6 8 10 12 14 16 p ro p o rt io n o f p a ti e n ts w it h ≥ 4 -p o in t im p ro ve m e n t in p o e m f ro m b a se lin e ( % ) weeks 84.0* 42.1 87.6* 44.2 *p < 0.0001 77.1* 77.8* *p < 0.0001 (a) (b) placebo+tcs dupilumab 300 mg q2w+tcs dupilumab 300 mg qw+tcs figure 5. proportion of patients achieving a ≥ 4-point improvement in poema (a) and dlqib (b) from baseline to week 16. 28.0 64.1* 55.3† 0 10 20 30 40 50 60 70 80 90 100 p ro p o rt io n o f p a ti e n ts r e p o rt in g n o p a in /d is c o m fo rt a t w e e k 1 6 (% ) *p < 0.0001 †p = 0.0004 placebo+tcs dupilumab 300 mg q2w+tcs dupilumab 300 mg qw+tcs 22/60 26/5635/56 figure 6. proportions of patients reporting “no pain/discomfort” on the eq-5d pain/discomfort subscale at week 16.a 29.6 18.6 62.6* 52.4† 59.1* 50.0 ‡ 0 10 20 30 40 50 60 70 80 90 100 café chronos café-like p a ti e n ts a c h ie vi n g e a s i75 ( % ) easi-75: similar in café (week 16) and chronos café-like populations (week 52) *p < 0.0001 †p = 0.0048 ‡p = 0.0008 32/ 108 23/ 46 11/ 21 11/ 59 67/ 107 65/ 110 placebo+tcs dupilumab 300 mg q2w+tcs dupilumab 300 mg qw+tcs figure 7. comparison of café and subgroup analysis of cafe-like patients in chronos. 0 2 4 6 8 10 12 14 16 l s m e a n p e rc e n t c h a n g e in s c o r a d sc o re f ro m b a se lin e ( m i) weeks –100 –90 –80 –70 –60 –50 –40 –30 –20 –10 0 –100 –90 –80 –70 –60 –50 –40 –30 –20 –10 0 0 2 4 6 8 10 12 14 16 l s m e a n p e rc e n t c h a n g e in e a s i sc o re f ro m b a se lin e ( m i) weeks *p < 0.0001 –46.6 –79.8* –79.8* –78.2* placebo+tcs dupilumab 300 mg q2w+tcs dupilumab 300 mg qw+tcs –29.5 –62.4* –62.4* –58.3* easi * p < 0.0001 scorad(a) (b) figure 3. least squares mean percent change in easi (a) and scorad score (b) from baseline to week 16. –100 –90 –80 –70 –60 –50 –40 –30 –20 –10 0 0 2 4 6 8 10 12 14 16 weeks –25.4–25.4 –53.9‡–53.9‡ –51.7‡–51.7‡ *p = 0.0214 †p = 0.0017 ‡p < 0.0001 * † l s m e a n p e rc e n ta g e c h a n g e in w e e k ly a ve ra g e o f p e a k p ru ri tu s n r s f ro m b a se lin e ( m i) placebo+tcs dupilumab 300 mg q2w+tcs dupilumab 300 mg qw+tcs figure 4. least squares mean percent change in weekly average of peak daily pruritus nrs from baseline at week 2 and week 16. table 2. overall summary of number of patients with aes through the 16-week treatment period – saf. references acknowledgments disclosures fc17posterregeneronsanofidebruin-wellerdupilumabwithconcomitanttopical.pdf skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 617 short communications onychomadesis as a manifestation of coxsackievirus a6 in an adult alfredo siller jr., md1; joseph jebain, md1; mojahed m. shalabi, bs2; stephen k. tyring, md, phd1,3 1center for clinical studies, webster, tx 2texas a&m college of medicine, dallas, tx 3department of dermatology, university of texas health science center at houston, houston, tx coxsackievirus (cv), also known as hand foot and mouth disease (hfmd), is generally considered to be a rare illness in adults. traditionally, hfmd has been strongly associated with enterovirus 71 and coxsackievirus a16 however, global outbreaks of a new virulent cva6 strain has been reported since 2008. cva6 has been shown to affect both children and adults and is associated with a more profound disease course that includes fever, sore throat, malaise, herpangina, a vesicular or maculopapular rash, and onychomadesis; a temporary cessation of nail growth that can lead to proximal separation of the nail plate from the nail matrix.1 a 32-year-old woman was referred to dermatology clinic for a painful rash of the hands and soles of four days duration, associated with malaise and subjective fevers. she denied any sick contacts. physical examination revealed erythematous papules, pustules and vesicles on the hands and feet (figure 1). additionally, tender, erythematous plaques were noted in the oral mucosa. two days prior, the patient presented to the emergency department and was suspected to have secondary syphilis, however, rapid plasma reagin (rpr) returned non-reactive. serological assay by complement fixation (cf) for coxsackievirus b (cvb) showed increased antibody titers for cvb 1, 2, 3, 5, 6, and 13. cf for coxsackievirus a (cva) 2, 4, 7, 9, 10, 16 antibodies was negative, however, quantitative reverse transcriptase polymerase chain reaction (rt-pcr) analysis and sequencing of buccal swabs returned positive for cva6. at follow-up one month later, she developed increased tenderness and partial desquamation of the hands and feet. re-examination revealed loosening and shedding of the proximal nails, consistent with onychomadesis (figure 2). the differential diagnosis for onychomadesis includes high fever, severe systemic disease, drug-induced reaction (e.g. introduction case presentation discussion skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 618 figure 1: illustrative example of the classic hand foot and mouth disease palmar rash seen in our patient. ramirez-fort, m. k., et al, journal of clinical virology, 60(4), 381-386. reproduced with permission from elsevier. chemotherapy, anticonvulsants etc.), infections, and idiopathic causes.2 a study of a hfmd outbreak of children in taiwan showed that the incidence of onychomadesis following cva6 infection was 37 percent (48/130) compared to 5 percent (7/145) in non-cva6 infections. additionally, 69 percent (33/48) of patients who developed onychomadesis were reported to experience concomitant palmoplantar desquamation before or at the time of nail changes.3 another study of a hfmd outbreak, in spain, noted differences in the prevalence of onychomadesis in regard to age with a 55% (18/33) occurrence rate seen in the youngest age group (9–23 months), 30% (8/27) in the middle age group figure 2: onychomadesis in the fingernails of our patient with coxsackievirus a6 (purple arrows) (24–32 months), and 4% (1/28) in the oldest age group (33–42 months). the causative agent for the hfmd outbreak in spain was not cva6 related, but rather other cv strains such as cvb1 and cvb2.4 the definitive diagnostic method of choice for detecting cva6 is rt-pcr from serum, skin scrapings, or buccal swabs. other diagnostic methods include rpr and serological assay by complement fixation.1 hfmd-induced onychomadesis is typically self-limited and usually no treatment is indicated. management of cva6 patients includes patient reassurance, hydration, and supportive care. the mean latency period of onychomadesis ensuing hfmd ranged from 1 to 2 months, average length 40 days, with only an average of 4 nails shed per case.4 to date only a small number of reports of hfmd-induced onychomadesis in adults have been described in the dermatological literature. despite its low numbers, there has been a rise in incidence of hfmd in adults due to the more virulent strain, cva6. it is reported that 11 percent of exposed adults become infected with hfmd however, fewer than 1% develop clinical manifestations.1 the precise mechanism of onychomadesis in hfmd remains a mystery, but several skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 619 hypotheses have suggested fever, inflammation, or direct damage from viral replication as potential culprits.2 conflict of interest disclosures: none funding: none corresponding author: alfredo siller jr., md 451 north texas ave webster, tx 77598 email: asillermd@gmail.com references: 1. ramirez-fort, m.k., et al., coxsackievirus a6 associated hand, foot and mouth disease in adults: clinical presentation and review of the literature. journal of clinical virology, 2014. 60(4): p. 381-386. 2. chiu, h.-h., et al., onychomadesis following hand-foot-and-mouth disease. cutis, 2016. 97(5): p. e20-1. 3. wei, s.-h., et al., an outbreak of coxsackievirus a6 hand, foot, and mouth disease associated with onychomadesis in taiwan, 2010. bmc infectious diseases, 2011. 11(1): p. 346. 4. guimbao, j., et al., onychomadesis outbreak linked to hand, foot, and mouth disease, spain, july 2008. eurosurveillance, 2010. 15(37): p. 19663. mailto:asillermd@gmail.com présentation powerpoint acknowledgements and disclosures the study was funded by ucb pharma. this poster was originally presented as an e-poster at the 28th eadv congress, 9–13 october 2019, madrid, spain. the authors would like to acknowledge jessica gamage phd cmpp, of imed comms, an ashfield company, for medical writing support that was funded by ucb pharma in accordance with gpp3 guidelines. a blauvelt reports consultant and investigator fees from abbvie, aclaris, akros, allergan, almirall, amgen, arena, boehringer ingelheim, bristol-myers squibb, celgene, dermavant, dermira inc, eli lilly, flx bio, galderma, genentech/roche, glaxosmithkline, janssen, leo, meiji, merck sharp & dohme, novartis, pfizer, purdue pharma, regeneron, revance, sandoz, sanofi genzyme, sienna pharmaceuticals, sun pharmaceuticals, ucb pharma, valeant, vidac; and speaker fees from janssen, regeneron, sanofi genzyme. ka papp reports consultant honoraria from abbvie, akros, amgen, arcutis, astellas, baxalta, boehringer ingelheim, bristol-myers squibb, canfite, celgene, coherus, dermira, dow pharma, eli lilly, forward pharma, galderma, genentech, janssen, kyowa hakko kirin, leo, merck (msd), merck-serono, mitsubishi pharma, novartis, pfizer, prcl research, regeneron, roche, sanofi aventis/genzyme, sun pharma, takeda, ucb pharma, valeant/bausch health; speaker fees from abbvie, amgen, astellas, celgene, eli lilly, galderma, janssen, kyowa hakko kirin, leo, merck (msd), novartis, pfizer, sanofi aventis/genzyme, sun pharma, valeant/bausch health; investigator grants from abbvie, akros, allergan, amgen, anacor, arcutis, astellas, baxalta, boehringer ingelheim, bristol-myers squibb, canfite, celgene, coherus, dermira, dow pharma, eli lilly, galderma, genentech, gilead, glaxosmithkline, janssen, kyowa hakko kirin, leo, medimmune, merck (msd), merck-serono, moberg pharma, novartis, pfizer, prcl research, regeneron, roche, sanofi aventis/genzyme, sun pharma, takeda, ucb pharma, valeant/bausch health; advisory board honoraria from abbvie, amgen, astellas, boehringer ingelheim, bristol-myers squibb, celgene, dow pharma, eli lilly, galderma, janssen, merck (msd), novartis, pfizer, regeneron, sanofi aventis/genzyme, sun pharma, ucb pharma, valeant/bausch health; and other fees from abbvie, akros, amgen, anacor, boehringer ingelheim, celgene, coherus, eli lilly, janssen, kyowa hakko kirin, merck (msd), merck-serono, novartis, pfizer, regeneron, sanofi aventis/genzyme, sun pharma, valeant/bausch health. jf merola reports consultant honoraria from abbvie, almirall, celgene, eli lilly, glaxosmithkline, janssen, merck, novartis, samumed, sanofi regeneron, sun pharma, ucb pharma; investigator honoraria from biogen idec, celgene, incyte, novartis, pfizer, sanofi regeneron; and other financial benefit from abbvie. a gottlieb reports consultant/advisory board agreements/or speakers bureau agreements with abbvie, allergan, avotres therapeutics, beiersdorf, bristol-myers squibb, celgene, dermira, eli lilly, incyte, janssen, leo, novartis, reddy labs, sun pharmaceutical industries, ucb pharma, valeant, xbiotech; and research/educational grants from boehringer ingelheim, incyte, janssen, novartis, xbiotech, ucb pharma. n cross and c madden are employees of ucb pharma. l peterson and c cioffi are employees and stockholders of ucb pharma. cem griffiths reports advisory board honoraria from abbvie, almirall, celgene, eli lilly, galderma, janssen, novartis, pfizer, sandoz, ucb pharma; speaker honoraria from abbvie, almirall, bristol-meyers squibb, celgene, eli lilly, galderma, janssen, novartis, pfizer, sandoz, ucb pharma; and other grants from abbvie, celgene, eli lilly, janssen, leo, novartis, pfizer, sandoz, ucb pharma. bimekizumab provides rapid and sustained improvements in scalp and nail outcomes in patients with moderate-to-severe plaque psoriasis: 60-week results from a randomized, doubleblinded, phase 2b extension study andrew blauvelt,1 kim a papp,2 joseph f merola,3 alice b gottlieb,4 nancy cross,5 cindy madden,5 luke peterson,5 christopher cioffi,6 christopher em griffiths7 synopsis ● psoriasis of the scalp and nails are associated with substantial physical, psychosocial and functional impairments affecting patients’ quality of life (qol)1,2 ● scalp and nail psoriasis are considered difficult-totreat areas and can be challenging to manage effectively with current therapies3,4 ● interleukin (il)-17a and il-17f are expressed in psoriasis lesional skin and synergize with other cytokines to amplify inflammation; preclinical data support neutralization of both il-17a and il-17f as a novel targeting approach in psoriasis5 ● bimekizumab is a monoclonal igg1 antibody that potently and selectively neutralizes both il-17a and il-17f6 ● bimekizumab was associated with rapid, substantial and durable clinical responses in patients with moderate-to-severe plaque psoriasis in the 12-week be able 1 (nct02905006) and 48-week be able 2 extension (nct03010527) phase 2 studies, with no unexpected safety findings7,8 1oregon medical research center, portland, or, usa; 2probity medical research and k papp clinical research, waterloo, on, canada; 3harvard medical school, brigham and women's hospital, boston, ma, usa; 4department of dermatology, icahn school of medicine at mount sinai, new york, ny, usa; 5ucb pharma, raleigh, nc, usa; 6ucb pharma, brussels, belgium; 7dermatology centre, university of manchester, manchester, uk methods ● in be able 1, patients were randomized to placebo or bimekizumab 64 mg, 160 mg, 160 mg with a 320 mg loading dose (ld), 320 mg or 480 mg7 (figure 1) ● in be able 2, be able 1 pasi90 responders remained on the same dose up to week 60, except for those previously randomized to bimekizumab 480 mg, who received 320 mg from week 128 (figure 1) ● presence of scalp or nail psoriasis at baseline (week 0) was defined as a psoriasis scalp severity index (pssi) score >0 or a modified nail psoriasis severity index (mnapsi) score of >0, respectively ● the following outcomes were assessed in week 12 responders: – resolution of scalp psoriasis (defined as pssi of 0) – resolution of nail psoriasis (defined as mnapsi of 0) – complete skin clearance (defined as a score of 0 on both absolute pasi and the investigator’s global assessment [iga]) – dermatology life quality index (dlqi) of 0 or 1 (representing no impact of psoriasis on healthrelated qol) ● non-responder imputation and observed data are presented results patients ● at the start of be able 2 (week 12), across all treatment groups, 133 of 217 patients (61.3%) were pasi90 responders ● of these 133 be able 1 responders, 125 (94.0%) had scalp psoriasis and 80 (60.2%) had nail psoriasis at baseline (week 0) scalp and nail outcomes ● bimekizumab treatment provided considerable improvements in both scalp and nail psoriasis – the proportion of patients with scalp psoriasis at baseline who achieved resolution increased rapidly with bimekizumab treatment; responses were generally maintained up to week 60 (figure 2a) – the percentage of be able 1 responders with nail psoriasis at baseline achieving resolution increased over time across all bimekizumab dose groups, reaching 73–89% at week 60 (figure 2b) ● among pasi90 responders with both scalp and nail psoriasis at baseline, the majority (60–73%) achieved complete skin and nail clearance by week 60 (figure 3) ● resolution of scalp and nail psoriasis was associated with improved health-related qol, with 91% and 84% of patients, respectively, achieving dlqi of 0 or 1 by week 60 (figure 4) references 1. klaassen kmg et al. j eur acad dermatol venereol 2014;28:1690–1695; 2. sampogna f et al. acta derm venereol 2014;94:411–414; 3. aldredge lm et al. j dermatol nurs assoc 2018;10:189–197; 4. merola jf et al. dermatol ther 2018;31(3):e12589; 5. glatt s et al. ann rheum dis 2018;77:523–532; 6. glatt s et al. br j clin pharmacol 2017;83:991–1001; 7. papp ka et al. j am acad dermatol 2018;79:277–286; 8. blauvelt a et al. aad 2019 [op11180]. figure 1. be able 1 and be able 2 study design figure 2a. percentage of be able 1 responders with scalp psoriasis at baseline achieving resolution of scalp psoriasis over time (nri) q4w, every four weeks; teaes, treatment-emergent adverse events. 0 20 40 60 80 100 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 bimekizumab 64 mg (n=15) bimekizumab 160 mg (n=50) bimekizumab 320 mg (n=31) bimekizumab 480 mg/320 mg (n=29) 80.6 86.2 100 76.0 0 4 8 12 16 20 24 28 32 36 40 44 48 p a ti e n ts a c h ie v in g p s s i 0 ( % ) weeks from be able 1 / be able 2 baseline 0 20 40 60 80 100 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 bimekizumab 64 mg (n=9) bimekizumab 160 mg (n=41) bimekizumab 320 mg (n=13) bimekizumab 480 mg/320 mg (n=17)p a ti e n ts a c h ie v in g m n a p s i 0 ( % ) weeks from be able 1 / be able 2 baseline 84.6 76.5 88.9 73.2 0 4 8 12 16 20 24 28 32 36 40 44 48 the 160 mg treatment group includes patients who received 160 mg plus 320 mg loading dose. non-responder imputation. mnapsi, modified nail psoriasis severity index; pssi, psoriasis scalp severity index. figure 3. be able 1 responders with both scalp and nail psoriasis at baseline achieving complete skin and nail clearance (absolute pasi, iga, mnapsi and pssi scores of 0) at week 12 and week 60 (nri) the 160 mg treatment group includes patients who received 160 mg plus 320 mg loading dose. non-responder imputation. iga, investigators global assessment; mnapsi, modified nail psoriasis severity index; pasi, psoriasis area and severity index; pssi, psoriasis scalp severity index. 0.0 60.0 22.2 70.4 27.3 72.7 30.8 69.2 0 20 40 60 80 100 week 12 (be able 2 week 0) week 60 (be able 2 week 48) bimekizumab 64 mg (n=5) bimekizumab 160 mg (n=27) bimekizumab 320 mg (n=11) bimekizumab 480 mg/320 mg (n=13) figure 4a. be able 1 responders with scalp psoriasis at baseline (n=125) achieving resolution of scalp psoriasis (pssi=0) and dlqi score of 0 or 1 at weeks 12, 24 and 60 (pooled bimekizumab groups, observed data) 8.0 2.4 3.7 68.8 87.0 90.7 0 20 40 60 80 100 week 12 week 24 week 60 pssi>0 pssi=0 p a ti e n ts a c h ie v in g d l q i 0 / 1 ( % ) n=10 n=86 n=3 n=107 n=4 n=98 56.3 28.2 8.8 23.8 60.3 83.8 0 20 40 60 80 100 week 12 week 24 week 60 mnapsi>0 mnapsi=0 p a ti e n ts a c h ie v in g d l q i 0 / 1 ( % ) n=45 n=19 n=22 n=47 n=6 n=57 figure 4b. be able 1 responders with nail psoriasis at baseline (n=80) achieving resolution of nail psoriasis (mnapsi=0) and dlqi score of 0 or 1 at weeks 12, 24 and 60 (pooled bimekizumab groups, observed data) observed data. dlqi, dermatology life quality index; mnapsi, modified nail psoriasis severity index; pssi, psoriasis scalp severity index. bimekizumab 160 mg (responders)  160 mg; n=55 n=42 n=39 n=43 bimekizumab 160 mg (non-responders)  320 mg; n=14 bimekizumab 160 mg q4w (with 320 mg loading dose) bimekizumab 160 mg q4w be able 1 treatment period be able 2 treatment period be able 1 baseline be able 1 week 12 n=250 if <pasi75 at week 12 or later then withdraw from study treatment be able 1 week 60 n=40 n=43 n=43 bimekizumab 64 mg q4w bimekizumab 64 mg (responders)  64 mg; n=15 bimekizumab 64 mg (non-responders)  160 mg; n=19 bimekizumab 320 mg q4w bimekizumab 320 mg (responders)  320 mg; n=33 bimekizumab 320 mg (non-responders)  320 mg; n=6 placebo q4w placebo (responders)  placebo; n=0 placebo (non-responders)  160 mg; n=37 bimekizumab 480 mg q4w bimekizumab 480 mg (non-responders)  320 mg; n=8 bimekizumab 480 mg (responders)  320 mg; n=30 response in be able 1 determined treatment allocation in be able 2: ≥pasi90 = responders <pasi90 = non-responders be able 2 baseline be able 2 week 48 presented at fall clinical dermatology conference® 2019 │las vegas, nv, usa │ october 17–20, 2019 figure 2b. percentage of be able 1 responders with nail psoriasis at baseline achieving resolution of nail psoriasis over time (nri) n=125 n=123 n=108 n=80 n=78 n=68 p a ti e n ts w it h s c a lp a n d / o r n a il p s o ri a s is a t b a s e li n e a c h ie v in g c o m p le te s k in a n d n a il c le a ra n c e ( p a s i, i g a , m n a p s i a n d p s s i s c o re o f 0 ) (% ) objective • this post-hoc analysis evaluated scalp and nail outcomes over the 60-week treatment period in be able 1 responders (defined as patients who achieved a ≥90% reduction in psoriasis area severity index [pasi90] at week 12) conclusions • in be able 1 responders with scalp and/or nail psoriasis at baseline, bimekizumab provided rapid and substantial clinical benefit that was maintained for up to 60 weeks • the majority of these patients achieved resolution of their scalp and/or nail psoriasis during the treatment period • resolution of scalp and nail psoriasis was associated with improved health-related qol • these results provide further support for dual neutralization of il-17a and il-17f with bimekizumab as a novel approach for the treatment of patients with moderate-to-severe psoriasis, including difficult-to-treat areas skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 943 skinmages bilateral upper extremities linear eruption in a 12-year-oldboy faraz yousefian, do1, aurel apple, do2, ann lin, do, ms, faad3 1 center for clinical and cosmetic research, aventura, fl 2 st. barnabas hospital department of dermatology, bronx, ny 3 university of south florida department of dermatology and cutaneous surgery, tampa, fl wells syndrome, eosinophilic cellulitis, is infrequently reported in children and is characterized by sudden, recurrent, painful, or pruritic edematous plaques resembling cellulitis or erysipelas most commonly seen on the extremities.1 it also may be accompanied by systemic symptoms such as fever and arthralgia.2,3 histologically, flame figures are often present but are not pathognomonic.2,4 in this image, a twelve-year-old boy with a past medical history of asthma, presented with a pruritic rash for one day that started on his hands and spread to his upper extremity. no accompanied systemic symptoms. the patient’s mother stated the patient has sporadically had similar episodes on the face and arms for the past 3-4 years, which improved with tapering a course of oral prednisone. skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 944 the physical exam revealed warm linear erythematous plaques located bilaterally on the patient’s hands, forearms, and upper arms (figure 1). two 3 mm punch biopsies of the right upper medial arm were performed which captured the perivascular and interstitial infiltrates of lymphocytes and eosinophils in the superficial dermis on hematoxylin and eosin stain (figure 2). the exact pathogenesis of wells syndrome is unknown.2 it is proposed that this condition is due to various triggers, such as arthropod assault, medications, allergic contact dermatitis, or underlying myeloproliferative infections.1 it is believed that il-2 leads to eosinophil degranulation through signaling effects.5 insect bites-correct. insect bites, vaccination, hypersensitivity reaction, fungal infections, parasite infestations, and viral infections have been most commonly reported to be associated with wells syndrome.1-3 along with history, clinical picture, and dermatopathology examination could help confirm the diagnosis of wells syndrome. cbc with differential cell counts can be ordered as a follow-up order since peripheral eosinophilia to a moderate degree (1500 to 5000 cells/mm3) has been reported in about half of the patients.2,3 wells syndrome has a good prognosis and a spontaneous resolution of 1-2 months.1,3 in severe cases, the initial treatment is prednisone 10-80mg daily or a tapering course which results in drastic improvement within a few days.3 conflict of interest disclosures: none funding: none corresponding author: faraz yousefian, do 2925 aventura blvd ste 205 aventura, fl, 33180 email: yousefian.faraz@gmail.com references: 1. šajn m, luzar b, zver s. wells’ syndrome possibly caused by hematologic malignancy, influenza vaccination or ibrutinib: a case report. world j clin cases. 2022;10(30):10997-11003. 2. safran t, masckauchan m, maj j, green l. wells syndrome secondary to influenza vaccination: a case report and review of the literature. hum vaccin immunother. 2018;14(4):958-960. 3. heinig b, vojvocic a, lotti t, tirant m, wollina u. wells syndrome an odyssey. open access maced j med sci. 2019;7(18):3002-3005. 4. watanabe y, yamamoto m, igari s, yamamoto t. two cases of wells syndrome with marked swelling in the hands. indian dermatol online j. 2020;11(6):979-982. 5. simon hu, plötz s, simon d, et al. interleukin-2 primes eosinophil degranulation in hypereosinophilia and wells’ syndrome. eur j immunol. 2003;33(4):834-839. secondary efficacy outcomes from a phase 2b, randomized dose-finding study of tapinarof cream for the treatment of plaque psoriasis linda stein gold, md;1 neal bhatia, md;2 anna m. tallman, pharmd;3 david rubenstein, md, phd4 1henry ford health system, detroit, mi, usa; 2therapeutics clinical research, san diego, ca, usa; 3dermavant sciences, inc., new york, ny, usa; 4dermavant sciences, inc., durham, nc, usa introduction ■ psoriasis is a chronic, immune-mediated disease characterized by scaly, erythematous, and pruritic plaques that can be painful and disfiguring1 ■ the burden of psoriasis is comparable to other long-term conditions, such as congestive heart failure and chronic lung disease, and has a profound impact on the mental health and wellbeing of those affected2 ■ although multiple options are available for the treatment of plaque psoriasis, there is a need for effective topical therapies that can be used without body surface area (bsa) restrictions or concerns for the duration of treatment ■ tapinarof cream is a novel therapeutic aryl hydrocarbon (ahr) receptor modulating agent (tama) under investigation for the treatment of psoriasis (clinicaltrials.gov id: nct03956355) and atopic dermatitis ■ this previously conducted phase 2b, double-blind, six-arm, dose-finding, vehiclecontrolled randomized study (clinicaltrials.gov id: nct02564042) assessed the efficacy and safety of tapinarof cream in subjects with plaque psoriasis3 ■ secondary efficacy outcomes support the primary endpoint analysis, which demonstrated that tapinarof cream was efficacious and well tolerated in adults with psoriasis and may represent an effective option in the topical treatment of the disease3 objectives ■ to report the additional efficacy outcomes of mean physician global assessment (pga) scores and mean change from baseline in pga, ≥50%, ≥75%, and ≥90% reduction in psoriasis area and severity index (pasi) from baseline (pasi50, pasi75, and pasi90), target lesion grading scores, and pruritus numeric rating scale (nrs) score methods study design ■ in this multicenter (united states, canada, and japan), phase 2b, double-blind, vehiclecontrolled randomized study, adult subjects with psoriasis were randomized 1:1:1:1:1:1 to receive tapinarof cream 0.5% or 1% once (qd) or twice daily (bid) or vehicle qd or bid for 12 weeks and followed up for 4 more weeks (figure 1) figure 1. study design tapinarof 1% bid (n=38) tapinarof 1% qd (n=38) tapinarof 0.5% bid (n=38) tapinarof 0.5% qd (n=38) vehicle bid (n=37) vehicle qd (n=38) offtreatment adult subjects with stable plaque psoriasis for ≥6 months • aged 18–65 years • bsa ≥1%–≤15%* • pga ≥2 (n=227) r double-blind treatment (12 weeks) follow-up (4 weeks) *excluding scalp. bid, twice daily; bsa, body surface area; pga, physician global assessment; qd, once daily. study outcomes and statistical analysis ■ the primary endpoint was pga response rates at week 12, defined as the proportion of subjects with a pga score of clear or almost clear (0 or 1) and ≥2-grade improvement in pga score from baseline to week 123 ■ additional efficacy outcomes reported here include mean pga scores, mean change in pga from baseline to week 12, pasi50, pasi75 and pasi90 response rates at week 12, total and mean target lesion grading scores change from baseline to week 12, and ≥4 improvement in pruritus nrs score from baseline to week 12 where baseline nrs score ≥4 ■ incidence, frequency, and nature of adverse events (aes) and serious aes were collected from the start of study treatment until the end of study visit at week 16 – investigators assessed the overall degree of application-site irritation using a scale from 0=no irritation to 4=very severe at each study visit – subject-reported tolerability on a 5-point scale from 0=none to 4=strong/severe was used to assess the presence and degree of application-site burning/stinging and itching within 2 hours following application of tapinarof or vehicle ■ p values for differences between tapinarof cream groups and the corresponding vehicle group for pasi response rates were calculated post hoc using barnard’s and fisher’s exact tests. p values for pga scores and total target lesion grading scores were based on a post-hoc analysis of covariance with main effect of treatment and covariates of average baseline selected score and pooled country. where p values were not available, differences between arms were considered statistically significant if 95% confidence intervals excluded 0 results subject characteristics ■ a total of 227 subjects (of 290 screened) were randomized (intent-to-treat population); of those randomized, 175 subjects (77%) completed the study, including the week 16 follow-up visit ■ mean demographic and baseline characteristics were comparable across treatment groups (table 1) ■ overall, 15% of subjects had a baseline pga category of 2 (mild), 80% had a pga category of 3 (moderate), and 5% had a pga category of 4 (severe) ■ baseline mean pasi score was 8.8 (standard deviation [sd] 4.5) table 1. baseline subject demographics and characteristics tapinarof 1% cream tapinarof 0.5% cream vehicle bid (n=38) qd (n=38) bid (n=38) qd (n=38) bid (n=37) qd (n=38) mean age, years (sd) 45.9 (11.9) 48.5 (10.6) 49.6 (10.9) 48.7 (9.7) 46.7 (12.6) 46.4 (10.2) male sex, n (%) 26 (68) 26 (68) 24 (63) 25 (66) 23 (62) 29 (76) mean weight, kg (sd) 85.6 (22.5) 86.7 (22.6) 88.6 (27.4) 89.3 (23.1) 87.8 (28.3) 91.6 (21.6) pga, mean (sd) 2.9 (0.4) 2.7 (0.5) 3.0 (0.5) 2.9 (0.4) 3.0 (0.3) 2.8 (0.4) pasi, mean (sd) 10.6 (5.0) 8.5 (3.6) 8.2 (4.5) 7.9 (4.8) 9.0 (4.3) 8.7 (4.4) % bsa affected, mean (sd) 8.2 (4.5) 6.5 (3.3) 7.2 (4.5) 6.1 (4.3) 6.6 (3.6) 7.0 (4.6) pruritus score, mean (sd)* 5.6 (2.6) 4.4 (2.9) 6.2 (2.2) 4.5 (2.6) 5.5 (2.8) 4.9 (2.4) total target lesion grading score, mean (sd)† 8.6 (1.3) 8.3 (1.5) 8.7 (1.9) 8.6 (1.2) 8.8 (1.1) 8.5 (1.4) baseline disease characteristics provided for the mitt population (n=196), which included subjects in the itt population minus the subjects from one site due to protocol violation. demographics (age, sex, and weight) provided for the safety population (n=227). *mean scores based on an nrs of 0 ‘absent’ to 10 ‘worst imaginable’; data provided for subjects with available results (n=32, 35, 30, 32, 29, and 32, respectively). †erythema, scaling, and induration plaque thickness; maximum score of 12 with higher score indicating increased severity. bid, twice daily; bsa, body surface area; itt, intent-to-treat; mitt, modified intent-to-treat; nrs, numeric rating scale; pasi, psoriasis area and severity index; pga, physician global assessment; qd, once daily; sd, standard deviation. pga response rates ■ primary endpoint: pga response rates (defined as pga score 0 or 1 and ≥2-grade improvement) at week 12 were significantly higher (at 0.05 significance level) in the tapinarof cream groups than the vehicle groups (65% [1% bid], 56% [1% qd], 46% [0.5% bid], 36% [0.5% qd] vs 11% [vehicle bid] and 5% [vehicle qd]) and were maintained for 4 weeks after the end of study treatment in all active treatment groups except for the 0.5% bid group3 pga scores ■ mean improvements in pga scores (sd) from baseline at week 12 were significantly higher in all tapinarof cream treatment groups compared with the vehicle groups: –1.8 (0.9) [1% bid], –1.7 (1.0) [1% qd], –1.7 (1.1) [0.5% bid], –1.3 (0.8) [0.5% qd] vs –0.5 (0.8) [vehicle bid] and –0.4 (0.7) [vehicle qd]; all comparisons p<0.001 pasi50 response rates ■ pasi50 response rates at week 12 were significantly higher in all tapinarof cream treatment groups compared with the vehicle groups (83% [1% bid], 92% [1% qd], 85% [0.5% bid], 71% [0.5% qd] vs 32% [vehicle bid] and 10% [vehicle qd]; all comparisons p<0.001), and were maintained up to the week 16 post-treatment follow-up figure 2. pasi75 response rates at week 12 and week 16 (follow-up) tapinarof 1% bid (n=23) tapinarof 1% qd (n=25) tapinarof 0.5% bid (n=26) tapinarof 0.5% qd (n=28) vehicle bid (n=19) vehicle qd (n=20) 65** 56*** 46* 46** 16 5 63*** 58*** 46* 54*** 5 11 p ro p o rt io n o f su b je ct s, % 60 70 80 90 100 50 40 30 20 10 0 week 12 week 16 (post-treatment follow-up) difference vs vehicle is statistically significant at *p<0.05, **p<0.01, ***p<0.001. n is number of subjects with available results at week 12. bid, twice daily; pasi75, ≥75% improvement in psoriasis area and severity index from baseline; qd, once daily. pasi75 response rates ■ pasi75 response rates at week 12 (figure 2) were significantly higher in all tapinarof cream treatment groups compared with the vehicle groups (65% [1% bid; p=0.001], 56% [1% qd; p<0.001], 46% [0.5% bid; p=0.035], 46% [0.5% qd; p=0.002] vs 16% [vehicle bid] and 5% [vehicle qd]) ■ significant pasi75 response rates were maintained up to the week 16 post-treatment follow-up (63% [1% bid; p<0.001], 58% [1% qd; p<0.001], 46% [0.5% bid; p=0.012], 54% [0.5% qd; p<0.001] vs 11% [vehicle bid] and 5% [vehicle qd]) pasi90 response rates ■ pasi90 response rates at week 12 were significantly higher in all tapinarof cream treatment groups compared with the vehicle groups, except the 0.5% qd group (39% [1% bid; p=0.002], 40% [1% qd; p=0.001], 31% [0.5% bid; p=0.008], 18% [0.5% qd; p=0.057 vs 0% [vehicle bid] and 0% [vehicle qd]), and were maintained up to the week 16 post-treatment follow-up (figure 3) ■ the time course of pasi50/75/90 responses with tapinarof generally showed a separation vs vehicle starting around week 2 with significantly superior efficacy maintained from week 12 through week 16 post-treatment follow-up pruritis nrs ■ in patients with a baseline pruritus nrs item score of ≥4, pruritus nrs response rates (defined as ≥4 improvement in pruritus nrs score from baseline) at week 12 were 55–73% in the tapinarof 1% treatment groups and 56–57% in the tapinarof 0.5% treatment groups compared with 33–60% in the vehicle treatment groups figure 3. pasi90 response rates at week 12 and week 16 (follow-up) 39** 40** 31** 18 0 0 38** 42** 27* 18 00 p ro p o rt io n o f su b je ct s, % 60 70 80 90 100 50 40 30 20 0 10 tapinarof 1% bid (n=23) tapinarof 1% qd (n=25) tapinarof 0.5% bid (n=26) tapinarof 0.5% qd (n=28) vehicle bid (n=19) vehicle qd (n=20) week 12 week 16 (post-treatment follow-up) difference vs vehicle is statistically significant at *p<0.05, **p<0.01. n is number of subjects with available results at week 12. bid, twice daily; pasi90, ≥90% improvement in psoriasis area and severity index from baseline; qd, once daily. total target lesion grading scores ■ greater reductions in total target lesion grading scores from baseline were observed in all tapinarof cream treatment groups vs the vehicle groups from week 2 onwards, with significantly greater reductions observed at week 12 (all comparisons p<0.001); significant differences were maintained up to the week 16 post-treatment follow-up (figure 4) figure 4. mean change in total target lesion grading scores† from baseline to week 12 and week 16 (follow-up) m e an c h an g e f ro m b as e lin e –3 –2 –1 –4 –5 –6 0 –7 –8 post-treatment follow-up week 0 1 2 4 8 –2.1 –2.5 –5.8*** ** *** *** *** 1612 tapinarof 1% bid (n=23) tapinarof 1% qd (n=25) tapinarof 0.5% bid (n=26) tapinarof 0.5% qd (n=29) vehicle bid (n=19) vehicle qd (n=20) –6.9*** –7.0*** –6.2*** difference vs vehicle is statistically significant at **p<0.01, ***p<0.001. n is number of subjects with available results at week 12. †erythema, scaling, and induration of plaque thickness. bid, twice daily; qd, once daily. safety ■ overall, 46% (104/227) of subjects had treatment-emergent aes (teaes): 56% in the tapinarof cream groups and 25% in the vehicle groups, and were mostly mild to moderate in severity ■ the most common treatment-related teaes were folliculitis (10% tapinarof vs 1% vehicle), contact dermatitis (3%; all tapinarof), and headache (1%; all tapinarof) ■ the majority of subjects had little to no investigator-assessed treatment-site irritation or self-reported application-site burning/stinging and itching throughout the study period with no apparent differences between tapinarof and vehicle groups conclusions ■ these results support the previously reported primary outcomes that tapinarof cream is efficacious and well tolerated in adults with plaque psoriasis3 ■ tapinarof cream resulted in clinically meaningful improvements in pasi50 and pasi75 from week 2, which were statistically significant in all tapinarof groups at week 12 through to week 16 post-treatment follow-up ■ post-hoc pasi90 response assessments followed a similar trend, showing early, durable and statistically significant response with tapinarof cream compared with vehicle ■ total target lesion grading scores improved from week 2 onwards with tapinarof cream compared with vehicle, and the difference was maintained up to week 16 ■ tapinarof cream was generally well tolerated with the majority of subjects having little to no irritation or burning/stinging and itching ■ these results suggest that tapinarof cream may provide an important potential advance in topical treatment for plaque psoriasis ■ a phase 3 study of tapinarof cream 1% qd in psoriasis is ongoing references 1. menter a et al. j am acad dermatol. 2008;58:829–850; 2. moon hs et al. dermatol ther. 2013;3:117–130; 3. robbins k et al. j am acad dermatol. 2019;80:714–721. acknowledgments the authors thank the participating investigators, patients and their families, as well as colleagues involved in the conduct of the study. editorial and medical writing support under the guidance of the authors was provided by apothecom, uk, and was funded by dermavant sciences, inc. in accordance with good publication practice (gpp3) guidelines (ann intern med. 2015;163:461–464). contact dr linda stein gold at lstein1@hfhs.org with questions or comments. skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 248 research letters caring for melanoma survivors with self-detected concerning moles during covid-19 restricted physician access: a cohort study june k. robinson, md1, burkhard jansen, md2 1department of dermatology, northwestern university feinberg school of medicine, chicago, il 2dermtech. inc., la jolla, ca self-management of melanoma detection with skin self-examination (sse) by melanoma survivors and other patients atrisk to develop melanoma depends on ready access to dermatologists when a concerning mole is detected.1 with the march 2020 illinois stay at home order (covid-19) inperson physician appointments for nonessential care ceased. additionally, there is uncertainty about when regularly scheduled health care would resume. dermatologists currently provide care under expanded telehealth benefits using electronic health record (ehr) portals for synchronous evisits.2 despite the limited quality of storeforward images,3 physicians attempted to interpret patient’s photographs and videos of concerning moles; however, improvements and objective assessments beyond image interpretation appear highly desirable. the cohort study of melanoma survivors presented here assessed sse anxiety prior to and during restricted physician access. it furthermore evaluated a telehealth support solution that enables patients to rule out melanomas and the need for surgical introduction background: physician appointments for non-essential care ceased during covid-19. objective: to pilot test a telehealth solution for patients to rule out melanomas and need for surgical biopsies based on genomic analyses of pigmented lesion samples obtained via adhesive patches. methods: surveys assessed sse anxiety. under remote clinician guidance, patients or partners obtained samples using adhesive patches (dermtech, la jolla, ca). results: sse anxiety increased. guided self-sampling led to molecular risk factor analyses in 7/7 (100%) of cases compared to 9/10 (90%) randomly selected physician-sampled control cases. conclusions: adhesive patch self-sampling under remote physician guidance is a viable specimen collection option. abstract skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 249 biopsies based on genomic analyses of pigmented lesion samples obtained noninvasively via adhesive patches. patients applied adhesive patches to confirmed skin lesions suspicious for melanoma under remote guidance by their dermatologist (jkr).4 (dermtech, inc. la jolla, ca.) melanoma survivors were trained to perform partner assisted sse and completed periodic online surveys assessing sse performance, identification of concerning moles, physician visits for moles, and biopsies of moles.5 sse anxiety and benefit were assessed (table 1). in march 2020, melanoma survivors submitted photographs of concerning moles that had changed or had moles reviewed via facetime by their dermatologist, who determined if the mole was clinically suspicious for melanoma. for confirmed concerning moles, the dermatologist ordered adhesive patch skin sample collection kits (dermtech, la jolla, ca) to be couriered to patients. patients or their skin check partners obtained the samples under remote clinician guidance. samples were returned by courier to dermtech for linc00518 and prame genomic risk factor analyses via dermtech’s pigmented lesion assay (pla).4 the dermatologist communicated test results and next steps to patients remotely. subjects were interviewed about their mole selfsampling experience. the institutional review board of northwestern university approved the research. melanoma survivors received $20 for each survey and those who submitted a specimen received $50. there were 211 respondents among 258 eligible melanoma survivors (81.7%). in the table 1. skin self-examination induced anxiety^ *2 p < .05 ^likert scale 1= strongly disagree, 3= neutral, 5 = strongly agree. adapted from promis anxiety measures. cella d, choi sw, condon dm, schalet b, hays rd, rothrock ne, et al. promis adult health profiles: efficient short-form measures of seven health domains. value health 2019; 22(5):537-544. 9 months preceding march 2020, 166 performed three sses. subjects were 54.5% female (115 of 211), had a mean age of 55 years, and 78.7% (166) had regularly scheduled appointments for skin examinations. all studied melanoma sse anxiety topics increased during covid -19 and there was a statistically significant difference in sse anxiety for 3 self-reported responses prior to and during covid-19 (table 1). sse anxiety in recent months, … prior to covid-19 mean (sd) (n=258) during covid-19 mean (sd) (n= 211) checking for moles caused me some distress. 1.2 (0.3) 3.1 (0.2)* checking for moles made me very concerned about having a melanoma. 1.9 (0.4) 4.3 (0.6)* i felt fearful when i checked my skin. 1.3 (0.2) 2.1 (0.9) i found it hard to focus on anything else other than my anxiety when i checked my skin. 1.1 (0.1) 1.8 (0.1) my worries overwhelmed me when i checked my skin. 1.2 (0.2) 1.3 (0.2) i felt uneasy when i checked my skin. 1.4 (0.3) 3.4(1.5)* sse benefit: decision to seek health care i i feel that checking my moles has helped me to better be able to decide if a mole needs to be checked by a doctor. d 4.6 (0.7) 4.8 (0.2) methods results 3.4 (1.5)* skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 250 table 2. comparison of mole self-sampling specimens with physician provided samples a) pla patient self-sampling under the remote supervision of a licensed healthcare professional sample # sex lesion size (mm) lesion location linc prame pla sample 1 m 5 x 5 hip nd nd n sample 2* f 5 x 5 shoulder nd nd n sample 3§ m 7 x 9 leg nd nd n sample 4§ m 7 x 7 scalp nd nd n sample 5 f 7 x 8 back nd nd n sample 6 f 6 x 11 back nd nd n sample 7* f 7 x 7 back nd nd n b) randomly selected physician collected pla control samples received during the same time period^ sample # sex lesion size (mm) lesion location linc prame pla control 1 m 10 x 10 back nd nd n control 2 f 9 x 10 ankle qns qns qns control 3 f 10 x 7 back nd d p control 4 f 6 x 7 leg nd nd n control 5 f 11 x 12 back nd nd n control 6 f 11 x 13 buttock nd nd n control 7 m 6 x 4 flank d nd p control 8 f 6 x 5 breast nd d p control 9 f 12 x 11 back nd nd n control 10 m 13 x 11 back nd nd n abbreviations: pigmented lesion assay (pla), long intergenic non-coding rna 518 / linc00518 (linc), preferentially expressed antigen in melanoma (prame), male (m), female (f), quantity not sufficient (qns), detected (d), not detected (nd), positive (p), negative (n), same patient. *§ ^ samples collected in states without restricted physician access. after covid-19, five subjects noted change in a mole. subjects related that lack of physician access influenced subjects’ decision to do mole self-sampling. guided self-sampling led to successful molecular risk factor analyses by pla in 7/7 (100%) of cases compared to 9/10 (90%) randomly selected physician-sampled control cases received during the same timeframe (table 2). in this study, increased sse anxiety may be partially attributed to generalized health anxiety; however, lack of physician access to provide skin examinations for melanoma survivors with self-identified concerning moles was an important factor in patients’ desire for high-quality alternatives. a limitation was lack of general anxiety assessment. this research demonstrates discussion skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 251 that adhesive patch self-sampling under physician guidance is a viable specimen collection option. remote collection can expand access to assessment by pla, a gene expression – based melanoma rule-out test with a negative predictive value above 99%, that reduces avoidable surgical biopsies of pigmented lesions clinically suspicious for melanoma by over 90% as demonstrated in a recent registry study of 3,418 cases.6 this proof-of-concept research demonstrates that patients are able to reliably perform selfsampling of concerning moles under remote physician supervision. patient-obtained skin sample collection using adhesive patches was successful in 100% of cases enabling actionable molecular pathology pla test reports to rule-out melanoma in all cases. the offered teledermatology solution provided pigmented lesion management with a negative predictive value of over 99% and reduced patient anxiety while avoiding office visits during a period when office visits are limited by covid-19 to essential care. adhesive patch self-sampling under remote clinician guidance is a viable specimen collection option. acknowledgment: supported by r01 ca154908 to june k. robinson, md, from the united states national cancer institute. pigmented lesion assay testing provided by dermtech inc. (la jolla, ca). mary kwasny, phd, department of preventive medicine, northwestern university, feinberg school of medicine, chicago, il, provided statistical analysis and received compensation for her role. conflict of interest disclosures: dr. jansen is an employee of dermtech, inc. dr. robinson has no conflicts of interest. clinical trials registration: nct02854657 corresponding author: june k. robinson, md department of dermatology northwestern university feinberg school of medicine 645 n michigan ave, suite 1050 chicago, il, 60611 usa email: june-robinson@northwestern.edu references: 1. robinson jk, wayne jd, martini mc, hultgren ba, mallett ka, turrisi r. early detection of new melanomas by patients with melanoma and their partners using a structured skin self-examination skills training intervention: a randomized clinical trial. jama dermatol. 2016;152(9):979-985. 2. president trump expands telehealth benefits for medicare beneficiaries during covid-19 outbreak. march 17, 2020. https://www.cms.gov/newsroom/pressreleases/president-trump-expands-telehealthbenefits-medicare-beneficiaries-during-covid-19outbreak 3. de carvalho tm, noels e, wakkee m, udrea a, nijsten t. development of smartphone apps for skin cancer risk assessment: progress and promise. jmir dermatol. 2019;2 (1):e13376. 4. gerami p, yao s, polsky d, et al. development and validation of a noninvasive 2-gene molecular assay for cutaneous melanoma. j am acad dermatol. 2017;76:114-20. 5. robinson jk, reavy r, mallett ka, turrisi r. remote partner assisted skin self-examination skills training of melanoma survivors and their partners. australian j dermatol. 2019;60 (1):e8082. 6. brouha b, ferris lk, skelsey mk, et al. realworld utility of a non-invasive gene expression test to rule out primary cutaneous melanoma: a large us registry study. j drugs dermatol. 2020 march, 19 (3). conclusion mailto:june-robinson@northwestern.edu powerpoint presentation integrating the 40-gene expression profile (40-gep) test into management of high-risk cutaneous squamous cell carcinoma aaron s. farberg, md1,2; mary a. hall, phd, mba3; leah douglas4; kyle r. covington, phd3; sarah j. kurley, phd3; robert w. cook, phd3; scott m. dinehart, md1 1icahn school of medicine at mount sinai, new york, ny; 2arkansas dermatology skin cancer center, little rock, ar; 3castle biosciences, inc., friendswood, tx; 4baylor college of medicine, houston, tx synopsis this study was sponsored by castle biosciences, inc., which provided funding to contributing centers for tissue and clinical data retrieval. mah, krc, sjk, and rwc are employees and options holders of castle biosciences, inc.. these data were previously presented, in part, at the 2019 american society for dermatologic surgery annual meeting, chicago, il, october 24-27, 2019. methods results references funding & disclosures conclusions 1. rogers et al. 2015 jama dermatol pmid: 25928283 2. karia et al. 2013 j am acad dermatol pmid: 23375456 3. waldman et al. 2019 hematol oncol clin n am pmid: 30497667 4. american cancer society. https://www.cancer.org/cancer/ 5. muzic et al. 2017 may clin proc pmid: 28522111 6. nccn guidelines. squamous cell skin cancer v1.2020 7. skin cancer foundation. https://www.skincancer.org/ 8. us census bureau. https://www.census.gov/ 9. wysong et al. 2019 american society for dermatologic surgery annual meeting 10. karia et al. 2018 jama dermatol pmid:29261835 11. ruiz et al. 2019 jama dermatol pmid: 30969315 12. jambusaria et al. 2013 jama dermatol pmid: 23325457 13. karia et al. 2014 jco pmid: 24366933 table 1. cohort demographics of 300 nccn high-risk cscc cases figure 1. study design of the 40-gep discovery, development, and validation • cutaneous squamous cell carcinoma (cscc) is the 2nd most common skin cancer, with ~1,000,000 cases diagnosed per year in the u.s.1-8 incidence is growing rapidly (>5-fold increase in past 30 years) and it surpasses the incidence of invasive melanoma. • regional metastasis rates of 13% have been reported, with most studies reporting <6% and most events occurring within 2-3 years of initial diagnosis and treatment.6 disease-specific mortality is 1.5-2% and the number of deaths from cscc per year is similar to that from melanoma.3,7 • national comprehensive cancer network (nccn) guidelines accommodate a broad range of treatment plan options for high-risk patients and recommend risk-directed implementation. these guidelines and the american joint committee on cancer (ajcc) and brigham and women’s hospital (bwh) staging systems have low positive predictive value (ppv) for identifying patients at high risk for metastasis (nccn 15%9; ajcc 14-17%10-11; bwh 24-38%11-13). • improved stratification for implementation of risk-appropriate treatment plans for patients with nccn-defined high-risk cscc is needed. • integration of the recently validated 40-gene expression profile (40-gep) test with ajcc or bwh t stage criteria into management of nccn high-risk cscc patients may be key to identifying those high-risk patients who would most benefit from aggressive treatment strategies, while concomitantly reducing unnecessary interventions for those who are low risk for poor outcomes. acknowledgements adult and pediatric dermatology: dr. toyohara brook army medical center: drs. xia and dalton brigham and women’s hospital: dr. schmults cedars-sinai: dr. gharavi cleaver dermatology: dr. cleaver columbia university: dr. samie dermasap: dr. reed dermatology and skin health: dr. mendese emory dept. of dermatology: dr. blalock indiana university school of medicine: dr. somani mayo clinic, jacksonville: dr. fosko medical college of wisconsin: dr. kasprzak metroderm pc: dr. papadopoulos miami beach skin center: dr. rivlin michael j. fazio, md: dr. fazio moffitt cancer center: drs. messina and zager mount sinai: dr. khorasani northwestern university: dr. yoo oakview dermatology: dr. trotter ohsu: dr. bar pariser derm: dr. pariser penn state: dr. neves porter adventist: dr. campana sfvahcs: dr. arron skin cancer specialists: dr. griego st. louis university: dr. ramona the indiana skin cancer center: dr. michael thomas jefferson university: dr. curry university of pennsylvania: dr. newman university of california, san francisco: dr. arron university of missouri: drs. smith, edison and braudis university of rochester: dr. ibrahim university of vermont medical center: dr. weinberger university of pittsburg medical center: dr. bibee university of southern california: dr. wysong university of tennessee health science center: dr. fleming university of tennessee medical center: dr. lewis zitelli and brodland, p.c.: drs. zitelli and brodland • integration of the 40-gep test into risk-directed management plans for nccn high-risk cscc patients identified a group of patients (class 1, t1/t2) with risk approaching that of the general population, thereby warranting a low intensity management strategy and sparing these patients unnecessary procedures and potential adverse effects. • conversely, those patients with rates of metastasis surpassing 50% (class 2b) warrant a high intensity strategy that increases follow-up visits, utilizes imaging and/or biopsies for nodal assessment, and offers adjuvant treatments and clinical trials for probable metastatic events. • the data presented herein support integration of the 40-gep into management of nccn high-risk cscc patients for implementation of risk-appropriate treatment plans for these patients. objective: to integrate a validated, prognostic 40-gene expression profile test into clinical decision making for risk-appropriate management of nccn high-risk cscc patients figure 2. kaplan-meier analysis of metastasis-free survival (mfs) by 40-gep class (n=321)9 40-gep class n 3-year mfs overall event rate class 1 203 91.6% 8.9% class 2a 93 80.6% 20.4% class 2b 25 44.0% 60.0% m e ta s ta s is -f re e s u rv iv a l p<0.0001 class 1 class 2a class 2b 100% 80% 60% 40% 20% 0% 0 1 2 3 4 5 years feature of modeling cohort (% of cohort) age: median years (range) 70 (34-95) sex: male 219 (73%) immune deficient 76 (25%) located on h&n 201 (67%) tumor diameter* : mean cm (≥2 cm) 1.85 (36%) tumor thickness**: mean mm (>6 mm) 3.90 (16%) poorly differentiated 36 (12%) clark level iv / v 62 (21%) pni present 36 (12%) subcutaneous fat invasion 43 (14%) 40-gep result class 1 189 (63%) class 2a 87 (29%) class 2b 24 (8%) *275 cases had tumor diameter reported;**109 cases had thickness reported. nccn, national comprehensive cancer network; h&n, head and neck; pni, perineural invasion; gep, gene expression profile 40-gep risk class and ajcc t stage (risk for metastasis**) recommended management plan low intensity management for 50% of patients: minimal clinical follow up (1-2x per year) reduced imaging (low frequency or none) reduced nodal assessment (palpation only) avoidance of adjuvant radiation or chemotherapy moderate intensity plan: clinical follow up (2-4x per year for 3 years) baseline and annual nodal us/ct for 2 years consider nodal biopsy or elective neck dissection consider adjuvant radiation or chemotherapy high intensity management for 8% of patients: increased clinical follow up (4-12x per year for 3 years) baseline and 4x per year nodal us/ct for 2 years offer nodal biopsy or elective neck dissection offer adjuvant radiation, chemotherapy, and/or clinical trials class 1 t1-t2 (7.5%) class 1 t3-t4 (16.7%) class 2a t1-t2 (15.6%) class 2a t3-t4 (34.8%) class 2b t1-t2 (50.0%) class 2b t3-t4 (87.5%) patient with high-risk cscc per nccn* perform 40-gep figure 4. risk-aligned management recommendations based on 40-gep and t stage prognosis a. cohort stratification and metastasis rate by 40-gep class and t stage 40-gep class ajcc t stage* bwh t stage* overall rate* t1-t2 t3-t4 t1-t2a t2b-t3 class 1 9% (189) 7.5% (159) 16.7% (30) 8.1% (173) 18.8% (16) class 2a 21% (87) 15.6% (64) 34.8% (23) 17.8% (73) 35.7% (14) class 2b 63% (24) 50.0% (16) 87.5% (8) 58.8% (17) 71.4% (7) *metastasis incidence and number (n) of patients in each class and per t stage. b. management intensity determined by risk for metastasis figure 3. integration of 40-gep prognostication into patient management decisions for nccn high-risk cscc patients (n=300) • the 40-gene expression profile (40-gep) test was developed and validated to stratify a patient’s risk for regional or distant metastasis at 3 years after diagnosis as low (class 1), high (class 2a), or highest (class 2b) risk for metastasis (figures 1 and 2).9 • as nccn high-risk cscc patients are the intended population for the 40-gep test, cases categorized as such (n=300, table 1) were used to analyze the effects of integration of 40-gep risk stratification into patient management decision making. all cases were staged according to either ajcc or bwh staging system criteria for t stage. the numbers of patients in each class/t stage combination along with metastasis rates were reported and used to align each patient group with risk-appropriate management recommendations. • risk-aligned management recommendations based on 40-gep results and t stage were developed for low, moderate, and high intensity management within the boundaries of acceptable nccn patient management approaches for patients with high-risk localized disease. metastasis rates of <10%, 10-50%, and >50% were aligned with low, moderate, and high intensity management recommendations, respectively. ongoing validation: • additional archival specimens • prospective studies 1. targeted approach qpcr analysis of 73 literature-identified genes 2. global approach microarray and deep learning→ qpcr validation of 67 genes primary ffpe cscc tissue w/ outcomes discovery expression from 140 genes for model development development deep learning model performance w/ 10x cross-validation training cohort (archival, n=122) final gene set and predictive algorithm validation independent validation (archival, n=321) evaluate assay performance *patients having a single nccn high-risk feature (e.g., immunodeficiency, ≥2 cm tumor diameter, tumor of the mask area or genitals, or poor tumor differentiation) are deemed high risk by nccn. **risk for metastasis is reported for 40gep class and ajcc 8th edition t stage. n=149 n=127 n=24 n=168 n=108 n=24 n=16857.7% 34.3% 8.0% 53.0% 39.0% 8.0% 40-gep + ajcc 40-gep + bwh low intensity (<10% risk) moderate intensity (10-50% risk) high intensity (>50% risk) n=159 n=173 n=117 n=103 n=24n=24 https://www.cancer.org/cancer/ https://www.skincancer.org/ https://www.census.gov/ ¾ tazarotenic acid plasma concentrations were more than two times higher after twice daily 1-minute contact than after once daily 1-minute contact (table 1). ¾ tazarotenic acid exposure (auc0-24) after multiple twice daily, 1-minute applications of dfd-03, was 83.21% of exposure following multiple once daily, 12-hour applications of tazorac cream (table 1). ¾ the cmax after multiple twice daily applications of dfd-03 was 62.99% of the cmax of multiple once daily applications of tazorac cream (table 1). ¾ erythema was the most common ae in this study, reported by nine subjects (64%) following twice daily 1-minute application of dfd-03, five subjects (33%) following once daily, 12-hour application of tazorac cream, and no subjects following once daily 1-minute application of dfd-03 (table 2). dfd-03 (0.1% tazarotene), twice-daily, short-contact lotion formulation, showed similar pharmacokinetic exposure (auc0-24) to the marketed cream product tazorac® (tazarotene) with once daily overnight application srinivas sidgiddi, md1; usha ranganathan, md1; anirudh gautam, mpharm2 1promius pharma, a subsidiary of dr. reddy’s laboratories, princeton, nj, usa 2dr. reddy’s laboratories sa., basel, switzerland conclusions ¾ the parameters auc0-24 and cmax of dfd-03 lotion were significantly impacted by frequency of dosing. systemic exposure to tazarotenic acid appeared to be dependent on the duration of dosing for all treatments. ¾ dfd-03, lotion formulation applied twice daily for 1-minute showed similar pharmacokinetic exposure (auc0-24) to tazorac cream with once daily overnight application. methods table 1. summary of the statistical analysis of tazarotenic acid – day 14 ¾ this was a single center, randomized, multiple dose, laboratory-blinded, open-label, 3-arm, parallel design study with 16 healthy subjects in each arm. ¾ in each treatment group, approximately 5 g of test product was applied to the face, neck, shoulders, upper chest and upper back (approximately 15% body surface area) on days 1 through 14. ¾ in treatment group 1, dfd-03 lotion was applied twice daily, 12 hours apart, and rinsed off after 1-minute contact. ¾ in treatment group 2, dfd-03 lotion was applied once daily and rinsed off after 1-minute contact. ¾ in treatment group 3, tazorac cream was applied once daily and rinsed off after 12-hours contact. ¾ blood samples were collected on days 1, 7 and 14, prior to product application and for up to 24 hours after product application. financial support: this study was funded and sponsored by the dr. reddy’s laboratories group of companies drl publication #815 results introduction ¾ the american academy of dermatology states that retinoids are the core of topical therapy for acne. ¾ common side effects include erythema, peeling, and dryness. ¾ results of a phase 1 bioavailability study comparing dfd-03 (tazarotene 0.1%) lotion twice daily (1-minute application), dfd-03 lotion once daily (1-minute application), and tazorac cream once daily (overnight application), are presented here. parameter cv (%) geometric ls means comparison ratio (%) 90% confidence limits (%)treatment group 1 treatment group 2 treatment group 3 lower upper cmax 54.7 164.20 77.72 260.66 1 vs 2 211.26 151.58 294.45 54.7 164.20 77.72 260.66 1 vs 3 62.99 45.48 87.26 54.7 164.20 77.72 260.66 2 vs 3 29.82 21.39 41.56 auc0-24 53.6 3797.48 1492.58 4563.57 1 vs 2 254.42 199.60 324.31 18.9 3797.48 1492.58 4563.57 1 vs 3 83.21 57.63 120.15 71.4 3797.48 1492.58 4563.57 2 vs 3 32.71 24.18 44.24 system organ class meddra preferred term treatment group 1 (n=14); n (%) treatment group 2 (n=14); n (%) treatment group 3 (n=14); n (%) subjects with at least 1 ae 10 (71) 4 (29) 6 (40) skin and subcutaneous tissue disorders 10 (71) 3 (21) 5 (33) erythema 9 (64) 0 5 (33) dry skin 0 3 (21) 0 skin burning sensation 2 (14) 1 (7) 0 pruritus 1 (7) 1 (7) 0 rash 1 (7) 0 0 skin discomfort 1 (7) 0 0 skin irritation 0 0 1 (7) nervous system disorders 2 (14) 1 (7) 2 (13) burning sensation 1 (7) 0 1 (7) dizziness 1 (7) 1 (7) 0 hyperaesthesia 1 (7) 0 1 (7) musculoskeletal and connective tissue disorders 0 0 1 (7) arthralgia 0 0 1 (7) respiratory, thoracic, and mediastinal disorders 1 (7) 0 0 nasal discomfort 1 (7) 0 0 table 2. summary of adverse events by system organ class fc17posterpromiussidgiddidfdovernightapplication.pdf microsoft word 2. 704 proof done.docx skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 4 in-depth reviews recent advances in systemic therapy for malignant melanoma umair khan, ba, 1 shivani b. kaushik, md,1 rina anvekar, md1 1department of dermatology, icahn school of medicine at mount sinai, new york, ny, usa melanoma arises due to mutations in the pigment producing skin cells called melanocytes. it is the most aggressive and deadliest skin cancer but accounts for only 1% of all cutaneous cancers. advanced melanoma has a poor prognosis with a median overall survival of 8-10 months and a 5-year survival rate of 10%.1 thus, early identification and treatment of melanoma is crucial in improving patient prognosis. in this article, we will discuss the various novel systemic treatments for advanced melanoma. the skin’s melanocytes rest in a microenvironment that is abundant in antigen-presenting dendritic cells, which helps facilitate activation of tumor specific cytotoxic t lymphocytes. these cytotoxic t lymphocytes (ctls) are involved in immune checkpoints that optimize the strength and quality of the antitumor response. the immune response has inhibitory checkpoint molecules such as ctla-4, pd-1 and lag3, and has stimulatory checkpoint molecules such as cd28, ox-40, and 4-1bb. as tumor cells try to disrupt and evade the regulatory checkpoints, therapeutic blockade of these efforts restores robust effector t-cell response (helper t cells and ctls). t cell activation or inhibition by the antigen presenting cells requires two signals. first, between the t cell receptor (tcr) and either the stimulatory checkpoint molecule cd28 or the inhibitory molecule ctla-4.2,3 then this tcr complex interacts with the major histocompatibility complex (mhc) expressed on antigen presenting cells (apcs) to initiate the ctl response. immunotherapy helps ctls perform two tasks in order to eradicate tumor cells: recognizing the presence of tumor cells and introduction malignant melanoma is a major contributor of skin cancer related mortality with increasing incidence and resistance to therapy. advanced melanoma has a poor prognosis with a median overall survival of 8-10 months and a 5-year survival rate of 10%. a better understanding of melanomagenesis and the tumor microenvironment has led to the development of several new therapies for metastatic melanoma. this review will provide a comprehensive overview of fda approved novel systemic therapies for advanced melanoma as well as of other classes of molecules under clinical investigation. this paper will also identify the key signaling pathways these therapies target and briefly discuss the utility of biomarkers in guiding targeted therapy. abstract skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 5 killing them via tumor cell lysis. the tumor infiltrating lymphocytes (tils) capacity for proliferation, cytokine production, and tumor lysis is limited by the suppressive effects of the tumor microenvironment (tme).4 tils that are removed from the limiting tme and grown ex vivo redevelop their anti-tumor activity suggesting that the tme leads to tcell exhaustion5. this notion drives the utility of adoptive t-cell therapy that aims to raise t-cells primed against melanoma ex vivo or in vitro and then injected back into patients to restore t-cell anti-tumor activity, such as tumor infiltration and lysis. the us food and drug administration has recently approved several novel immunotherapies, such as ipilimumab and nivolumab. these monoclonal antibodies restore robust infiltration of the tme by tils, which leads to positive responses in some patients.2 immunotherapy is unique because it offers durable responses in patients, but the number of patients who respond are lower in comparison to other modalities of treatment.6,7 these advances offer physicians several new options alongside traditional therapeutic approaches such as surgical resection, chemotherapy, radiotherapy, and photodynamic therapy. two types of barriers limit the efficacy of advanced melanoma therapy, and these include adverse events (aes) and increased drug resistance. ae’s most commonly lead to skin and gastrointestinal toxicity, due to the non-specific anti-tumor immune response.8 as can be expected, ae’s occur less frequently in monotherapy than in combination therapy, particularly when utilizing immunotherapy. systemic melanoma therapies are summarized in tables 1 and 2 and are described in detail below: anti-cytotoxic t lymphocyte associated protein 4/ ctla-4 inhibitors ctla-4 is normally only active on the surface of specific regulatory t-cells, but in patients with melanoma, ctla-4 is also activated on the surface of ctls present in the tme. the ctla-4 receptor signaling pathway plays a crucial role in inducing immunological tolerance of tumors by suppressing ctl activation.9,10 thus, ctla-4 inhibits t-cell activation and evokes immune tolerance in the tme. ipilimumab is a monoclonal antibody that blocks ctla-4, thereby enhancing the production of pro-inflammatory t-cell cytokines that promote clonal expansion and infiltration of tumors by ctls. it was fdaapproved for treatment of metastatic melanoma in march, 2011. the approval was based on data from ten prospective and two retrospective studies that showed patients on ipilimumab had a median survival rate of 11.4 months and a 3-year survival rate of 22%, both significantly higher than the treatment in naïve or previously treated groups.11 in another study on patients with resected stage iii melanoma with high risk of recurrence, ipilimumab treated patients were recurrence free for a median of 26.1 months compared to the 17.1 months for the placebo group.12 aes observed in these trials include autoimmune alterations such as colitis, dermatitis, endocrinopathies, and neuritis. current trials are investigating the efficacy of ipilimumab in conjunction with nivolumab, bevacizumab and others (nct01673854, nct02731729, nct00790010). pd-1 inhibitors effector t cells express another immune checkpoint molecule called programmed cell death-1 (pd-1), which suppresses t-cell activation by binding to its ligands pd-l1 and pd-l2 present on apcs in the tme. melanoma cells also express pd-1 when skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 6 induced by interferon-gamma, which is secreted by effector t cells. once tumor cells express pd-1, it is taken up by apcs, which travel to and bind the pd-1 ligand on effector t cells. this coupling inactivates ctls by changes to their metabolic signature and certain signaling cascades.13,14 this serves as a potent mechanism for suppressing the immune response to tumor pathogenesis. effector t-cell response to tumor cells can be restored by monoclonal antibodies that target the binding of pd-1 to pd-l1. in 2014, japan approved nivolumab, a monoclonal antibody that targets pd-1,for the treatment of unresectable melanomas. in one study with multiple arms, 28% (26/94) of the patients with melanoma had a positive response, compared to 18% (14/76) for patients with non-small cell lung cancer, and 27% (9/33) for patients with renal cell carcinoma.14 interestingly, another study showed nivolumab to be more efficient than ipilimumab with a median progression-free survival (pfs) of 6.9 month versus 2.9 months for ipilimumab, and 11.5 months for combination with nivolumab and ipilimumab. this study suggested that immune checkpoint blockers have additive effects. however, it’s important to note that 55.0% of patients in the nivolumab plus ipilimumab group experienced grade 3 or 4 treatmentrelated adverse events, higher than in the nivolumab (16.3%) or ipilimumab (27.3%) alone.15 thus, clinicians should pay close attention to the management of adverse events when using combination therapies. other anti-pd-1 molecules being studied in trials include js100, pembrolizumab, toripalimab, and nivolumab in conjunction with other immunotherapy or chemotherapy (nct03013101,nct02608268, nct02027961). additional immune checkpoints lymphocyte activation gene-3 (lag-3) and t cell immunoglobulin and mucin domain-3 (tim-3) are other inhibitory checkpoint molecules currently being studied as therapeutic targets. both suppress costimulatory signals in effector t cells much like ctla-4. both are also expressed by treg cells and play vital roles in immunosuppression (table2) (nct03708328, nct02817633). cancer vaccines (peptides and dendritic cell therapy) cancer vaccines prime ctls that recognize and attack antigenic tumor derived peptides presented on mhc molecules on the cancer cell surface. these vaccines can use peptides, proteins, mrna, or dna as the therapeutic target. melanoma cells express gp100, which is a cell surface glycoprotein found only in melanocytes and cells in the retina. epitopes in the cancer vaccine can amplify recognition of gp100 by ctls and increase tumor infiltration. preclinical data suggests limited efficacy of gp100 as monotherapy, but it may hold promise as an adjuvant therapy.16,17 combination therapies of gp100 with il-2, mage-3, resiquimod and others are currently underway (nct00470015,nct01176461, nct01176474, nct02535078). oncolytic virus therapy in oncolytic virus therapy a nonpathogenic viral strain is directly injected into a metastatic melanoma nodule, which selectively targets cancer cells for viral replication and subsequent tumor lysis. the spilled cell content contains neo-antigens and cytokines such as interferon gamma that evoke intense proliferation and infiltration of other tumor cells by tcls.18,20 talimogene laherparepvec (t-vec) is a genetically engineered oncolytic virus skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 7 derived from the herpes simplex family. it was approved by the fda in october 2015 for the treatment of unresectable melanoma. patients with metastatic melanoma were administered t-vec in a phase ii clinical trial, which displayed a 28% objective clinical response.19 this drug demonstrates the potential to induce durable responses in some patients and current trials are evaluating its efficacy in conjunction with antictla-4 antibody and other immunotherapy (nct02288897,nct03259425, nct03190824). in addition, some clinical trials are investigating similar monotherapies with coxsackievirus (nct01227551), and in combination with pembrolizumab or ipilimumab (nct02565992, nct02307149). co-stimulatory agents t-cell activation requires tcr signaling along with co-stimulatory signals such as glucocorticoid-induced tnrf-related gene (gitr). gitr is a stimulatory checkpoint molecule that prevents t-cell apoptosis thereby enhancing their activation and proliferation. in addition, when gitr is expressed by treg cells it weakens tme immunosuppression enabling t-cell infiltration and tumor lysis.21 trx518 is the monoclonal antibody for gitr that is currently being studied as monotherapy for metastatic melanoma (trx518-001) or in combination with pd-1 inhibitors (nct03277352). adoptive cell therapy adoptive cell therapy (act) increases the patient’s innate antitumor immune response by utilizing either autologous or allogenic tumor-reactive t or nk cells. although the exact mechanism of act’s antitumor activity is not fully understood, it may include suppression of tregs or changes in the tme cytokine profile that eliminates host immunosuppression.22 t cells are primed against cancer cells by in vitro stimulation using neo-antigens that include cancerantigenic peptides and tumor cells. these primed t cells are then injected into patients utilizing rosenberg til transfer therapy, which involves lymphocyte removal by immunosuppressants and total body irradiation. for these patients, the response rate was above 70%.23 currently, several trials are investigating the efficacy of cloned tcrs primed specifically against melanocyte differentiation antigens (nct02619058 & nct02652455). inhibiting immunosuppression within the tumor microenvironment metastatic melanoma patients are immunosuppressed by virtue of how cancer cells remodel their environment to allow for growth and proliferation.24 thus, the therapeutic value of cancer immunotherapy alone is limited, making it necessary to develop an approach for tme immunosuppression reversal. below is a brief overview of systemic therapies for inhibiting immunosuppression in the tme, which include targeting the signaling pathways involving either braf, mek, c-kit, pi3k, or ccr4. braf inhibitors braf mutations are present in up to 80% of melanoma patients and facilitate an immunosuppressive state within the tumor microenvironment by activating mitogenactivated protein kinase (mapk) pathway. this pathway then stimulates malignant transformation and proliferation. the most common braf mutation occurs at amino acid 600, where valine is substituted by glutamic acid (brafv600e mutation). the mapk signaling pathway leads to changes in the tme by disrupting dendritic cell production of anti-tumor cytokines il-12 and tumor necrosis factor alpha (tnf-α), resulting in weakened stimulation of tils.45 therefore, once the mapk signaling cascade skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 8 is blocked in brafv600e tumor cells, the immunosuppressive state is then attenuated. vemurafenib is an oral braf inhibitor approved by the fda in 2011 that has shown promise by increasing infiltration of cd8+ and cd4+ t cells in melanoma tissues of patients with brafv600e mutations. vemurafenib likely does this by stimulating expression of melanoma-specific antigens, which attracts effector t cells and nk cells, and reduces the production of immunosuppressive cytokines.25 in comparison to chemotherapy, vemurafenib has shown 24% longer pfs and overall survival (os) in clinical trials of brafv600e positive melanoma patients. furthermore, in brafv600e positive patients who received vemurafenib, clinical studies showed 90% tumor regression.26 other braf inhibitors that are in clinical trials include dabrafenib and encorafenib as monotherapy (nct01436656) and in combination with immunotherapy or chemotherapy(nct02902042, nct03235245, nct02631447). mek inhibitors mek is a downstream target of braf and has emerged as a target to overcome resistance to braf inhibitors. the fda approved trametinib, a selective mek1/2 inhibitor, as monotherapy for patients with metastatic melanoma and braf mutations. the blocking of mek 1/2 results in decreased tumor cell proliferation and reduced growth factor mediated cell signaling.25,27 in comparison to chemotherapy, trametinib was seen to significantly improve clinical response rate, pfs, and os.28 in addition, a clinical trial studying trametinib and dabrafenib showed durable responses and the fda approved this combination therapy in 2014 for patients with metastatic braf melanoma.29 current trials are evaluating its efficacy alongside cell cycle and immune checkpoint inhibitors (nct02159066). c-kit inhibitors patients with mucosal, acral lentiginous, or cutaneous melanoma arising in areas of sun damage may overexpress ckit, a tyrosine kinase receptor. mutations or gene amplifications in ckit also result in the constitutive activation of both mapk and pi3k/akt pathways.25,30,31 imatinib is an oral ckit inhibitor that has shown a 30% response rate and pfs of 3-4 months and is currently being studied in combination with chemotherapy and immunotherapy (nct00667953 & nct02812693).32,33 pi3k-akt-mtor pathway inhibitors activation of the mtor pathway has been characterized in patients with braf mutations and is associated with poor prognosis. mtor is activated by the pi3k/akt pathway and thus plays a pivotal role in tumor development and progression.33-35 presently, clinical trials aim to curtail this pathway and suggest that the anti-tumor effects of mtor may be enhanced when combined with the mapk pathway inhibitors.36 thus, mtor inhibitors such as everolimus or temsirolimus are being tested in combination with a braf inhibitor or chemotherapy (nct01390818 & nct01596140). anti-ccr4 antibodies ccr4 is a chemokine receptor expressed on t cells that helps regulate transport of leukocytes and is associated with a poor prognosis in t cell leukemia, renal cell carcinoma, and melanoma.37 currently, trials are evaluating the efficacy of the anti-ccr4 antibody for melanoma. it is suspected that since the receptor is expressed in tregs, its blockade may restore the immune response by preventing cancer cells from binding tregs and suppressing the effector t cell response.38 skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 9 chemotherapy the selection of a chemotherapy regimen involves understandings the efficacy of dosing, timing, delivery, and the utility of drug combinations. chemotherapy is a second line alternative to immunotherapy when treating patients with metastatic melanoma. the immunosuppressive effects of chemotherapies are varied and selective. many anticancer drugs can weaken the immune system. for example, cyclophosphamide, gemcitabine, or docetaxel will reduce the number of treg cells; and gemcitabine, docetaxel, or doxorubicin will reduce the number of myeloid-derived suppressor cells (mdscs).39,40 currently, dacarbazine is one of the most effective chemotherapy agents for melanoma patients. in a pooled analysis of numerous randomized controlled trials, dacarbazine monotherapy showed an objective response rate between 5.3% and 28%.41 although it showed poor efficacy alone, dacarbazine in combination with other modalities can cause durable responses in some patients.42 chemotherapies induce immunogenic cell death (icd), which is different from necrosis or apoptosis in that icd produces a more robust antitumor response via increased uptake of cancer cell antigens by dendritic cells (dcs) and increased activation of apc’s and t cells. icd also stimulates expression of calreticulin on the cell surface of tumor cells, which promotes phagocytosis by dcs. cell death also causes adenosine triphosphate (atp) to be released in the extracellular space as a signal to attract immune cells to the tumor. atp also primes the inflammasome by binding to a purine receptor and inducing il-1b production. this promotes t cell activation and proliferation. dcs are induced in a similar fashion with the release of high-mobility group box 1 protein (hmgb1) from tumor cells which bind to tolllike receptor 4 ligands on dcs. in addition to these extracellular chemokines, mitochondrial heat shock proteins such hsp70 and hsp90 are leaked, increasing antigen uptake by dc’s through complex formation with tumor derived antigens.43 ido inhibitors indoleamine 2,3 dioxigenase 1 (ido1) is an enzyme that converts tryptophan into kynurenine. ido1 is expressed by many tumor cells in addition to dcs and macrophages and tends to indicate a poor prognosis. in the tme, tumor cells expressing ido1 stimulate cytotoxic t lymphocytes (ctls) conversion of tryptophan into kynurenine. this depletion of tryptophan in ctls weakens their anti-tumor activity and results in an immunosuppressed environment, thereby presenting ido inhibition as a potential target for immunosuppression reversal.44 ido inhibitors are currently being studied in combination with checkpoint inhibitors to test their efficacy against metastatic melanoma (nct02073123). anti-csf1r antibodies colony-stimulating factor 1 (csf-1) receptor is a cell surface receptor, and both csf-1 and il-34 help tumor-associated macrophages (tam) with survival. tam’s play a pivotal role in maintaining the tumor immunosuppressive environment; thus, tumor growth can be limited by inhibiting tam’s (nct03101254). anti-vegf antibodies vascular endothelial growth factor (vegf) is a signal protein that stimulates the formation of blood vessels, which helps to mediate tumor growth and immune suppression. vegf inhibitors aim to directly suppress the metastasis and growth of tumor cells.46,47 bevacizumab is an anti-vegf monoclonal antibody that challenges tumor growth. a multicenter phase ii trial showed skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 10 bevacizumab and temozolomide had an objective response rate of 16%, a pfs of 4.2 months, and an os of 9.6 months.48 in another phase ii clinical trial, bevacizumab in combination with ifn α-2b showed a pfs rate of 4.8 months and an os rate of 17 months. although these studies failed to validate its use as monotherapy in metastatic melanoma, current trials are ongoing and studying bevacizumab use in combination with immunotherapy and chemotherapy (nct00026221,nct01048554, nct03175432,nct02681549, nct03167177). predictive biomarkers for immune checkpoint blockade the identification of biomarkers can help guide patient therapy towards specific treatments that show the greatest promise in producing a durable response. the braf v600e mutation, for example, is a predictive marker for response to braf inhibitors. however, many of these patients develop resistance over a variable period of time and thus require additional treatment options.49,50 treatment resistance can be divided into genomic, epigenetic, and immunologic factors. patients with melanoma who possess markers like nras/kras mutations, braf mutations, low levels of pd1l in the tme, or harmful epigenetic changes tend to become resistant to both chemotherapy and targeted therapy.51 thus, certain biomarkers not only inform selection of therapy but also the likelihood of developing resistance. the tumor microenvironment is another important indicator of drug potential and efficacy. the tme presents opportunities for therapeutic targets to induce infiltration by ctls and suppress cancer growth. interestingly, patients who respond the best to immunotherapy display robust tumor infiltration at presentation. in patients undergoing pd-1 therapy, those with cd8+ infiltration of the tme at presentation had the greatest pfs and os.53 another observation in these patients is that high numbers of somatic mutations prime tumor cells to express more neo-antigens, creating a host environment that may benefit greatly from targeted therapy.54-56 thus, to inform the selection of ideal therapy, clinicians should consider testing patients for important biomarkers and align this data with the patients genetic and immune status. elucidation of essential mechanisms in melanomagenesis has led to the development of novel targets in treatment. the introduction of immunotherapies targeting ctla-4 and pd-1 checkpoint inhibitors has ushered in a new era of melanoma treatment. utilizing melanoma patients’ genetic status and stratifying their anti-tumor immune responses may help guide first-line targeted therapy. despite these advances, malignant melanoma remains a lethal disease, especially when diagnosed at a late stage. further investigation of melanomagenesis and mechanisms of resistance represent a central goal for cancer research and may help more patients obtain durable responses in the future. conflict of interest disclosures: none funding: none corresponding author: shivani kaushik, md 1425 madison avenue, box 1047 department of dermatology new york, ny -10029 email: docshivanib@gmail.com conclusion skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 11 table 1. classification of systemic melanoma treatments abbreviations: ctla-4, cytotoxic t lymphocyte-associated antigen 4; gitr, glucocorticoid-induced tnfr-related gene; ido, indoleamine 2,3-dioxigenase; lag-3, lymphocyte activation gene-3; pd-1, programmed cell death-1; pd-l1, programmed cell death-1 ligand-1; tim-3, t-cell immunoglobulin and mucin domain-3; vegf, vascular endothelial growth factor; braf, proto-oncogene braf; mek, mitogen-activated protein kinase kinase; mtor, mammalian target of rapamycin. table 2. outcomes from key clinical trials for systemic treatments for melanoma abbreviations: ctla-4, cytotoxic t lymphocyte-associated antigen 4; pd-1, programmed cell death-1; braf, proto-oncogene braf; mek, mitogen-activated protein kinase kinase; vegf, vascular endothelial growth factor; dtic, dacarbazine function target agents development checkpoint blockers ctla-4 ipilimumab tremelimumab fda approved phase iii pd-1 nivolumab pembrolizumab pdr001 fda approved fda approved phase iii pd-l1 atezolizumab durvalumab avelumab phase ii phase ii phase ib lag-3 imp321 lag525 phase i phase ii co-stimulatory agents gitr trx518 phase i immunomodulators vegf bevacizumab phase ii braf vemurafenib fda approved mek trametinib fda approved mtor everolimus phase ii ido indoximod epacadostat phase i-ii chemotherapy methylating guanine at the o-6 and n-7 positions dacarbazine fda approved target treatment orr (%) pfs (months) os (months) ctla-458 ipilimumab + dtic or dacarbazine 15.2 10.3 3 (all) 11.2 9.1 pd-159 nivolumab or dacarbazine 40 13.9 5.1 2.2 not reached ctla-4 + pd160 ipilimumab or nivolumab or i+n 19 43.7 57.6 2.9 6.9 11.5 not reached braf61 vemurafenib or dtic 48 5 5.3 1.6 13.6 9.7 mek62 trametinib or dtic 22 8 4.8 1.5 81 67 mek + braf63 trametinib or dabrafenib + trametinib 51 64 7.3 11.4 18 25.6 skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 12 references: 1. garbe c, eigentler tk, keilholz u, hauschild a, kirkwood jm. systematic review of medical treatment in melanoma: current status and future prospects. oncologist. 2011;16:5–24 2. i. melero, s. hervas-stubbs, m. glennie, d.m. pardoll, l. chen, immunostimulatory monoclonal antibodies for cancer therapy, nat. rev. cancer 7 (2007) 95–106 3. t. nomura, k. kabashima, y. miyachi, the panoply of abt cells in the skin, j. dermatol. sci. 76 (2014) 4. 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366 (pg. 2443-54) 60. wolchok jd, kluger h, callahan mk, et al. nivolumab plus ipilimumab in advanced melanoma, n engl j med, 2013, vol. 369 (pg. 122-33) 61. chapman pb, hauschild a, robert c, et al. improved survival with vemurafenib in melanoma with braf v600e mutation, n engl j med, 2011, vol.364 (2507-16) 62. flaherty kt, robert c, hersey p, et al. improved survival with mek inhibition in braf-mutated melanoma, n engl j med, 2012, vol. 367 (pg. 107-14) 63. flaherty kt, infante jr, daud a, et al. combined braf and mek inhibition in melanoma with braf v600 mutations, n engl j med, 2012, vol. 367 (pg. 1694-703) acknowledgements: medical writing support was provided by prescott medical communications group (chicago, il) with financial support from ortho dermatologics; ortho dermatologics is a division of bausch health us, llc | presented at winter clinical dermatology conference 2020 • january 17-22, 2020 • kohala coast, hi synopsis ◾ current formulations of tazarotene (gel/foam/cream) can cause irritation, which may limit their use1 ◾ a novel tazarotene 0.045% lotion formulation was developed utilizing polymeric emulsion technology, resulting in a more uniform distribution of the active ingredient and of the moisturizing excipients at the skin’s surface2 ◾ in a 12-week phase 2 study (nct02938494) in participants with moderate-to-severe acne, tazarotene 0.045% lotion was superior to vehicle for the coprimary endpoints (reduction in inflammatory and noninflammatory lesions and treatment success per evaluator global severity score grading)2 ◾ in addition, tazarotene 0.045% lotion was as effective as tazorac® (tazarotene 0.1% cream), but with fewer adverse events2 objective ◾ to examine the participant-reported outcomes from this phase 2 study of tazarotene 0.045% lotion methods ◾ participants aged 12 years and older were randomized (2:2:1:1) to receive double-blind treatment with tazarotene 0.045% lotion, tazarotene 0.1% cream, lotion vehicle, or cream vehicle ◾ in this study, cerave® hydrating cleanser and cerave® moisturizing lotion (l’oreal, ny) were provided as needed for optimal moisturization/cleaning of the skin ◾ participant-reported outcomes included: oily/shiny skin, acne-specific quality of life questionnaire (acne-qol), and subject self-assessment (ssa) ◾ data were analyzed descriptively in participants with available data at week 12; data for the cream and lotion vehicles were combined for this analysis results ◾ the intent-to-treat population included 210 participants ◾ at week 12, the percentage of participants who reported “no oily or shiny skin on face” was similar between tazarotene 0.045% lotion and tazarotene 0.1% cream and greater than combined vehicle (figure 1a) • among participants with any oily/shiny skin, the percentage who were “not bothered at all” was higher with lotion than with cream or vehicle (figure 1b) ◾ mean changes from baseline to week 12 in acne-qol domains generally indicated greater improvement with both tazarotene formulations (lotion and cream) than with vehicle in all 4 domains (figure 2) ◾ per ssa ratings, the percentage of participants who reported having 90-100% clear skin was similar between tazarotene lotion and cream and greater than vehicle (figure 3) comparison of a novel tazarotene 0.045% lotion to tazarotene 0.1% cream: patient-reported outcomes from a phase 2 clinical trial figure 2. absolute mean change from baseline to week 12 in acne-qol (itt population) 0 2 4 6 12 10 8 self-perception role-emotional role-social acne symptoms 8.2 8.4 6.1 5.0 5.7 4.5 7.2 7.4 5.7 7.4 6.1 6.3 tazarotene 0.045% lotion (n=65) combined vehicle (n=61) a b so lu te m e a n c h a n g e f ro m b a se lin e tazarotene 0.1% cream (n=64) higher scores for each domain reflect improved health-related qol. no imputation of missing values. self-perception domain assesses the extent facial acne has affected a particular area of self-perception (eg, feeling self-conscious, feeling unattractive, dissatisfaction with self appearance).3 role-emotional domain assesses the emotional effect or impact of facial acne (eg, annoyance at spending time on face, worry/ concern about medications working fast enough, bothersomeness of needing cover-up).3 role-social domain assesses the impact of facial acne on a respondent’s intersocial relationships (eg, going out in public, meeting new people, socializing).3 acne symptoms assesses the physical symptoms experienced by facial acne (eg, bumps on face, scabbing, worry about scarring); the acne symptom domain score correlates inversely with acne severity.3 acne-qol, acne-specific quality of life questionnaire; itt, intent-to-treat. figure 1. percentage of participants reporting “none/no oily skin on face” (a) and “not bothered at all” by oily skin in the past week (b) (itt population) 0% 10% 20% 30% 40% baseline n=69 n=72 n=69 week 12 n=65 n=64 n=61 27.7% 7.2% 16.7% 8.7% 31.3% 18.0% tazarotene 0.045% lotion combined vehicle p e rc e n ta g e o f p a rt ic ip a n ts tazarotene 0.1% cream 0% 10% 20% 30% 40% baseline n=65 n=61 n=64 week 12 n=48 n=44 n=50 31.3% 13.8% 8.2% 23.4% 25.0% 24.0% p e rc e n ta g e o f p a rt ic ip a n ts tazarotene 0.045% lotion combined vehicle tazarotene 0.1% cream b. “not bothered at all” by oily skin in the past week a. none/no oily skin on face no imputation of missing values. itt, intent-to-treat. figure 3. percentage of participants reporting 90-100% clear skin on the ssa (itt population) 0% 10% 20% 30% 40% 50% baseline n=69 n=72 n=69 week 12 n=65 n=64 n=61 38.5% 0% 0% 1.4% 35.9% 24.6% tazarotene 0.045% lotion combined vehicle p e rc e n ta g e o f p a rt ic ip a n ts tazarotene 0.1% cream no imputation of missing values. itt, intent-to-treat; ssa, subject self-assessment. conclusions ◾ consistent with the clinician-assessed primary endpoints, participant-reported skin oiliness, qol, and acne severity were improved with tazarotene 0.045% lotion versus vehicle ◾ taken together with the improved tolerability and similar efficacy of tazarotene 0.045% lotion versus tazarotene 0.1% cream,2 this novel lotion formulation may be a viable new treatment option that is as effective as cream with fewer adverse events references 1. zaenglein al, et al. j am acad dermatol. 2016;74(5):945-973. 2. tanghetti ea, et al. j drugs dermatol. 2019;18(6):542-548. 3. acne-specific quality of life questionnaire (acne-qol) manual & interpretation guide. january 2003. http:// www.anzctr.org.au/steps11and12/376709-(uploaded-1101-2019-20-05-40)-study-related%20document.pdf author disclosures dr. zoe draelos received funding from ortho dermatologics to conduct the research presented in this poster. dr. fran cook-bolden has served as consultant, speaker, and/or investigator for galderma, leo pharma, almirall, cassiopea, ortho dermatologics, investigators encore, foamix, hovione, aclaris, and cutanea. dr. lawrence green has served as speaker, consultant, or investigator arcutis, abbvie, amgen, celgene, dermavant, jannsen, lilly, mc2, novartis, ortho dermatologics, sienna, sunpharma, and ucb dr. eric guenin is an employee of ortho dermatologics and may hold stock and/or stock options in its parent company. ms. gina martin and dr. radhakrishnan pillai are employees of bausch health us, llc and may hold stock and/or stock options in its parent company. zoe draelos, md1; fran cook-bolden, md2; lawrence green, md3; eric guenin, pharmd, phd, mph4; gina martin, mot5; radhakrishnan pillai, phd5 1dermatology consulting services, pllc, high point, nc; 2dept. of dermatology, mount sinai hospital center, new york, ny; 3dept. of dermatology, george washington university school of medicine, washington, dc; 4ortho dermatologics*, bridgewater, nj; 5bausch health us, llc*, petaluma, ca *bausch health us, llc is an affiliate of bausch health companies inc. ortho dermatologics is a division of bausch health us, llc. džɖŝđăů�'ƌğğŷ�dğă�wžůljɖśğŷžůɛ�ăŷě��ăīğŝŷğ�ăɛ�ă�dƌğăƚŵğŷƚ�ĩžƌ��đŷğ�sƶůőăƌŝɛ ^ăƌăś�z͘ 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ŵăƌŭğƚğě�ăɛ�zğɖůğŷŝdž��&�ăŷě�ăǀăŝůăďůğ�ŝŷ�đƌğăŵ�ăŷě�ɛğƌƶŵ�ĩžƌŵƶůăɵžŷɛ͘��ƌ͘ ��ƌžělj�ǁăɛ� ŝŷǀžůǀğě�ŝŷ�ƚśğ�đžŷđğɖƚƶăůŝnjăɵžŷ�ăŷě�ěğɛŝőŷ�žĩ�ƚśğ�ɖƌžěƶđƚ͘ references ϭ͘��žůžőŷŝă͕�:͕͘�:žƌŝnjnjž͕�:͘�>͕͘�θ�^đśăīğƌ͕ �:͘�s͘ �͕��ğƌŵăƚžůžőlj͘ �ϯϭϭϯ͕�wśŝůăěğůɖśŝă͗��ůɛğǀŝğƌ�^ăƶŷěğƌɛ͘ ϯ͘�>ăljƚžŷ͕��͘d͕͘�kɖɵŵăů�ŵăŷăőğŵğŷƚ�žĩ�ăđŷğ�ƚž�ɖƌğǀğŷƚ�ɛđăƌƌŝŷő�ăŷě�ɖɛljđśžůžőŝđăů�ɛğƌƶğůăğ͘��ŵ�:��ůŝŷ��ğƌŵăƚžů͕�ϯϭϭϭ͘�ϯ;ϯϳ͗�ɖ͘�ϭϯϱͳϰϭ͘ ϯ͘�dśŝďžƶƚžƚ͕��͘d͕͘�kǀğƌǀŝğǁ�žĩ�ăđŷğ�ăŷě�ŝƚɛ�ƚƌğăƚŵğŷƚ͘��ƶɵɛ͕�ϯϭϭθ͘�θϭ;ϭ�^ƶɖɖůϳ͗�ɖ͘�ϯͳϳ͘ ϰ͘�zžɛɛ͕�:͘/͕͘�ğƚ�ăů͕͘�wśğŷžƚljɖŝđ�ăŷě�őğŷžƚljɖŝđ�đśăƌăđƚğƌŝnjăɵžŷ�žĩ�ăŷɵďŝžɵđͳƌğɛŝɛƚăŷƚ�wƌžɖŝžŷŝďăđƚğƌŝƶŵ�ăđŷğɛ�ŝɛžůăƚğě�ĩƌžŵ�ăđŷğ�ɖăɵğŷƚɛ ����ăʃğŷěŝŷő�ěğƌŵăƚžůžőlj�đůŝŷŝđɛ�ŝŷ��ƶƌžɖğ͕�ƚśğ�h͘^͘�͕͘�:ăɖăŷ�ăŷě��ƶɛƚƌăůŝă͘��ƌ�:��ğƌŵăƚžů͕�ϯϭϭϭ͘�ϭϰϰ;ϯϳ͗�ɖ͘�ϯϯϵͳϰϲ͘ ϱ͘�^ƚƌăƶɛɛ͕�:͘^͕͘�ğƚ�ăů͕͘�'ƶŝěğůŝŷğɛ�žĩ�đăƌğ�ĩžƌ�ăđŷğ�ǀƶůőăƌŝɛ�ŵăŷăőğŵğŷƚ͘�:��ŵ��đăě��ğƌŵăƚžů͕�ϯϭϭϳ͘�ϱϲ;ϰϳ͗�ɖ͘�ϲϱϭͳϲϯ͘ ϲ͘��ăďƌğƌă͕��͕͘�z͘��ƌƚăđśž͕�ăŷě�z͘�'ŝŵğŷğnj͕��ğŷğįđŝăů�ğīğđƚɛ�žĩ�őƌğğŷ�ƚğăͳͳă�ƌğǀŝğǁ͘�:��ŵ��žůů�eƶƚƌ͕ �ϯϭϭϲ͘�ϯϱ;ϯϳ͗�ɖ͘�ϳϵͳϵϵ͘ ϳ͘�zžžŷ͕�: z͘͘ ͕�ğƚ�ăů͕͘��ɖŝőăůůžđăƚğđśŝŷͳϯͳőăůůăƚğ�ŝŵɖƌžǀğɛ�ăđŷğ�ŝŷ�śƶŵăŷɛ�ďlj�ŵžěƶůăɵŷő�ŝŷƚƌăđğůůƶůăƌ�ŵžůğđƶůăƌ�ƚăƌőğƚɛ�ăŷě�ŝŷśŝďŝɵŷő�w͘�ăđŷğɛ͘�: ����/ŷǀğɛƚ��ğƌŵăƚžů͕�ϯϭϭϯ͘�ϭϯϯ;ϯϳ͗�ɖ͘�ϰϯϵͳϰϭ͘ fc17postertopixsiutopicalgtpcaffeine.pdf powerpoint presentation survey results identifying clinician strategies for therapy selection for common inflammatory skin diseases disclosures references results nicholas d. brownstone1, aaron s. farberg2,3, ann p. quick4, jennifer j. siegel4, matthew s. goldberg4, peter a. lio5 1. temple university hospital, philadelphia, pa 2. baylor scott & white health system, dallas, tx 3. bare dermatology, dallas, tx 4. castle biosciences, inc, friendswood, tx 5. northwestern university feinberg school of medicine, chicago, il methods › in the absence of a molecular test to help guide therapeutic selection, clinicians currently must make empirical decisions based on personal experience and/or the available population-based evidence, which can lead to delays in disease control and increased cost to the healthcare system. › clinicians would prefer to have a molecular test to help determine the most efficacious drug for individual patients. › results from this survey can be used to inform clinical studies such as the prospective identity study which is currently enrolling patients with psoriasis and atopic dermatitis to use each patient’s molecular data to guide personalized therapeutic selection. conclusionsobjectives 1) to determine how clinicians currently choose a systemic therapy for patients with moderate-tosevere atopic dermatitis or psoriasis in the absence of routine molecular data and 2) to determine how often the current approach leads to patients switching medications. changing systemic therapy clinician interest in molecular test 1. renert-yuval y and guttman-yassky e. j am acad dermatol. 2020; 124(1):28-35. 2. armstrong a and read c. jama, 2020;323(19):1945-1960. 3. kaushik s and lebwohl m, j am acad dermatol, 2019; 80(1):27-40. 4. aggarwal p et al, dermatol ther 2022; 12, 611-614. 5. mathur s and sutton j, biomed rep. 2017; 7(1):3-5. › recent advances in the understanding of the molecular pathways underlying the development of common inflammatory skin diseases including atopic dermatitis (ad) and psoriasis led to the development of multiple novel systemic drugs targeting those pathways.1,2 › as more therapeutics are approved for treatment of ad and psoriasis, it will be important to make informed decisions about each individual patient’s therapeutic plan. › each patient’s molecular profile can impact the efficacy of a drug for that individual. however, literature suggests that patient comorbidities may be the driving factor for determining systemic medications.3 further, a low biopsy rate for uncertain inflammatory skin disease diagnoses may lead to incorrect diagnosis and treatment in a subset of patients.4 › a trial-and-error approach to therapy selection could lead to delay in appropriate treatment of ad or psoriasis and increased cost to healthcare systems.5 › therefore, understanding an individual patient’s disease at the molecular level could better inform treatment decisions. › however, currently, non-invasive molecular tests to guide therapeutic selection are not routinely used for psoriasis and atopic dermatitis. › a 20-question survey was submitted for human subject irb approval and deemed exempt by advarra irb. › the survey was made available to attendees of the winter clinical dermatology 2022 conference. › participation was voluntary and not associated with additional data presentation; respondents that completed the survey were given monetary compensation. background › this study was sponsored by castle bioscience, inc. › ndb has no relevant disclosures. › asf is a consultant for castle biosciences, inc. and on the advisory board for eli lilly, sun pharma, ortho dermatologics, boehringer ingelheim, incyte, amgen, galderma, novartis, janssen, and pfizer. › apq, jjs and msg, are employees and shareholders of castle biosciences, inc. › pal reports research grants/funding from abbvie, aobiome, eczema foundation, national eczema association; is on the speaker's bureau for abbvie, eli lilly, galderma, hyphens pharma, incyte, la roche-posay/l’oreal, myor diagnostics, parentmd, pfizer, pierrefabre dermatologie, regeneron/sanofi genzyme; reports consulting/advisory boards for abbvie, almirall, amyris, arbonne, aslan, bodewell, boston skin science, bristol-myers squibb, burt’s bees, castle biosciences, codex labs, concerto biosci, dermavant, dermira, dermveda, eli lilly, galderma, intraderm, janssen, johnson & johnson, kaleido biosci, kimberly clark, leo pharma, lipidor, l’oreal, menlo therapeutics, merck, micreos, myor diagnostics, regeneron/sanofi genzyme, sibel health, skinfix, sonica, theraplex, ucb, unilever, verrica, yobee care; stock options with learnskin/learn health, medable, micreos, modernizing medicine, yobee care. in addition, dr. lio has a patent pending for a theraplex product with royalties paid and is a board member and scientific advisory committee member of the national eczema association. results respondent demographics number years in practice n respondents (%) resident/ fellow 73 (27.6) 1-10 years 88 (33.2) 11-20 years 42 (15.9) 21-30 years 33 (12.5) >30 years 29 (10.9) primary specialty n respondents (%) dermatologist 235 (88.7) dermpath or derm/ dermpath 3 (1.1) np/pa 19 (7.2) mohs 1 (0.4) other specialist 7 (2.6) practice type n respondents (%) academic/university 94 (35.4) group practice 102 (38.5) multi-specialty group 28 (10.6) solo practice 40 (15.1) retired 1 (0.4) number patients with moderateto-severe ad or psoriasis / month n respondents (%) 0 5 (1.9) 1-10 88 (33.2) 11-24 100 (37.7) 25-49 41 (15.5) 50+ 31 (11.7) number biologics prescribed for ad or psoriasis / month n respondents (%) 0 9 (3.4) 1-10 126 (47.6) 11-24 96 (36.2) 25-49 22 (8.3) 50+ 12 (4.5) factors considered when choosing a first systemic therapy for ad or psoriasis were ranked on a scale from 1-5 from most important (1) to least important (5). ranked results were compiled and kruskal-wallis test was used to detect significant differences. “reported efficacy” was the highest-ranking factor while “molecular mechanism” ranked lower overall in the current decision-making process (p< .001). reason for systemic therapy discontinuation average number systemic therapies needed for efficacy percent all respondents that would find a molecular test for ad or psoriasis therapy guidance useful “no symptom improvement” was the top reason reported for patient discontinuation of systemic medications for ad or psoriasis. additionally, 62.3% (165) of clinicians surveyed estimated that, on average, 2 or more systemic therapies were needed to find one that was efficacious indicating that lack of efficacy for individual patients contributes to switching systemic therapies. greater than 90% (239) of all clinicians responded that they would or would likely find a molecular test for therapeutic selection for psoriasis or ad beneficial. factors currently guiding therapy selection side effects no symptom improvement financial burden insurance declined other slide 1 skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 548 research letters 755-nm alexandrite laser for the treatment of non-facial superficial and nodular basal cell carcinoma valerie shiu, md1, margaret e brown, md1, pavela bambekova, md1, jenny yeh, md1, jacqueline brogan, md1, catherine kowalewski, do2 1division of dermatology & cutaneous surgery, university of texas health science center at san antonio, san antonio, tx 2south texas veterans health care system, san antonio, tx laser therapy has a wide variety of clinical applications in dermatology. there is emerging literature regarding laser therapy as a treatment for non-melanoma skin cancer, particularly for patients who are not surgical candidates. the greatest promise has been shown in the treatment of basal cell carcinoma (bcc) with vascular and ablative lasers.1 in 2011, ibrahimi et al. abstract background: there is emerging literature regarding laser therapy as a treatment for non-melanoma skin cancer, with reports of vascular selective lasers and ablative lasers showing promise in basal cell carcinoma (bcc). objectives: to assess the efficacy of the 755-nm laser in the treatment of non-facial bcc of the superficial and nodular subtypes. to provide patients with a non-surgical option for the treatment of bcc. methods: nineteen veterans, each with at least one biopsy proven superficial or nodular bcc on the trunk or extremity, agreed to participate in our irb-approved, prospective, non-randomized, open-label clinical trial. a total of 21 bcc were treated, after local anesthetization, using the 755-nm alexandrite laser (gentle-lase, candela corporation) in a single session with a 4 mm margin. treatment sites were rebiopsied approximately six weeks later. results: twenty-one of 21 treated bcc demonstrated complete histologic tumor resolution at 6-week follow-up. at six weeks, all patients had a scar, and some patients had associated crusting, scaling or ulceration. the high energy and absence of dynamic cooling in our study likely resulted in additional thermal damage to the tumors. healing times and scar appearance were comparable to electrodesiccation and curettage sites. limitations: our study was limited by a small sample size, lack of a control group, and sampling of treatment sites with shave removal rather than complete excision. conclusion: the 755-nm laser has vessel-selective properties and a greater depth of penetration compared to vascular selective lasers. our study results suggest that the 755-nm alexandrite laser may be an effective treatment for superficial and nodular bcc on the trunk and extremities. further investigation is warranted. introduction skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 549 described success in treating multiple basal cell carcinomas in a single patient with basal cell nevus syndrome using the 755-nm alexandrite laser.2 no subsequent studies, to our knowledge, have further investigated the 755-nm laser in the treatment of bcc. we designed a prospective, nonrandomized, open-label clinical trial to further assess the efficacy of the 755-nm alexandrite laser in the treatment of nonfacial bcc of the superficial and nodular subtypes. the study was approved by the institutional review board at the south texas veterans health care system. nineteen veterans, each with at least one biopsy-proven superficial or nodular bcc on the trunk or extremity, agreed to participate in our study. exclusion criteria included tattoos overlying the affected or adjacent skin, photosensitivity, medications in which infrared light is a contraindication, pregnancy, light-induced seizure disorder, active infection of the treatment area, or if the treatment area was overlying an implantable cardiac device. a total of 21 bcc were treated. following local anesthetization with intralesional 1% lidocaine without epinephrine, the tumor site and a 4-millimeter margin of clinically normal-appearing surrounding tissue were treated in a single session using the 755-nm alexandrite laser (gentle-lase, candela corporation). the following settings, identical to the settings used in the initial report by ibrahimi et al., were utilized: 8 millimeter spot size, two passes at an energy of 100 j/cm2, pulse length of 3 milliseconds, no dynamic cooling mode, and 10% overlapping of treated tissue between pulses. treatment resulted in an eschar in all cases. post-laser wound care involved petrolatum jelly and a non-stick dressing. the treatment sites were then re-biopsied using a broad shave technique approximately six weeks later. twenty-one of 21 treated bcc demonstrated complete histologic tumor resolution (table i). clinically, treatment sites demonstrated similar healing as electrodesiccation and curettage sites, with healing over several weeks and resultant round scar (figure i). the subjects will continue to be followed at least twice annually for five years after the treatment. our study was limited by a small sample size, lack of a control group, and sampling of treatment sites with shave removal rather than complete excision. nonetheless, the results of our study suggest that the 755-nm alexandrite laser may be an effective treatment for superficial and nodular bcc on the trunk and extremities in patients who do not desire surgery, and we believe that further investigation is warranted. the alexandrite laser is known to have vessel-selective properties as well as a greater depth of penetration compared to vascular selective lasers, such as the pulsed-dye laser (pdl).2 these properties could explain the mechanism for the complete treatment of bcc in our subjects. additionally, the high energy in the absence of dynamic cooling likely resulted in significant thermal damage to the bcc sites. it is important to note that scar outcomes following the 755-nm alexandrite laser treatment of the bcc sites were not better than treating bcc sites with electrodesiccation and curettage (ed&c), and therefore the patient and the provider methods results discussion skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 550 table 1. patient location of bcc histologic subtype of bcc size of bcc (cm) clinical appearance immediately after treatment pathology, shave biopsy, 6 weeks after treatment clinical appearance 6 weeks after treatment 1 back superficial & nodular 0.4 x 0.4 eschar no residual bcc scar with scale 2 pue superficial 0.6 x 0.6 eschar no residual bcc scar 3 back superficial 1.3 x 1.2 eschar no residual bcc scar 4 shoulder superficial 1.5 x 1.5 eschar no residual bcc scar with crust 5 shoulder nodular 0.5 x 0.5 eschar no residual bcc scar with scale 6 back nodular 0.8 x 0.8 eschar no residual bcc scar with crust 7 due superficial 1.3 x 0.8 eschar no residual bcc scar with crust shoulder superficial 1.5 x 1.3 eschar no residual bcc scar with crust 8 clavicle superficial 1.1 x 0.6 eschar no residual bcc scar 9 back nodular 0.6 x 0.5 eschar no residual bcc scar 10 shoulder superficial 1.0 x 1.0 eschar no residual bcc scar pue superficial & nodular 0.5 x 0.5 eschar no residual bcc scar 11 shoulder superficial 2.0 x 1.7 eschar no residual bcc scar with eschar 12 back nodular 0.6 x 0.5 eschar no residual bcc scar 13 due superficial 1.5 x 1.5 eschar no residual bcc scar with eschar 14 back superficial & nodular 0.8 x 0.3 eschar no residual bcc scar with scale 15 shoulder nodular 0.9 x 0.7 eschar no residual bcc scar with eschar 16 pue superficial 1.0 x 1.0 eschar no residual bcc scar with eschar 17 chest nodular 0.4 x 0.4 eschar no residual bcc scar with eschar 18 back superficial & nodular 0.5 x 0.5 eschar no residual bcc scar 19 back superficial & nodular 0.7 x 0.5 eschar no residual bcc scar pue, proximal upper extremity; due, distal upper extremity skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 551 figure 1. pre, immediately post, and 6 weeks post procedural images of bcc sites treated with laser therapy. should consider the cost effectiveness between different treatment modalities when making decisions regarding bcc treatments. conflict of interest disclosures: none funding: none corresponding author: pavela bambekova, md dermatology clinic, mays cancer center 7979 wurzbach rd., mail code 7876 san antonio, tx 78229 bambekova@uthscsa.edu references: 1. soleymani t, abrouk m, kelly km. an analysis of laser therapy for the treatment of nonmelanoma skin cancer. dermatol surg. 2017 may;43(5):615-624. doi: 10.1097/dss.0000000000001048. 2. ibrahimi oa, sakamoto fh, tannous z, anderson rr. 755 nm alexandrite laser for the reduction of tumor burden in basal cell nevus syndrome. lasers surg med. 2011 feb;43(2):6871. doi: 10.1002/lsm.2095 mailto:bambekova@uthscsa.edu patient tolerability of tazarotene foam, 0.1%, and impact on patient compliance real world patient perceptions of the use of calcipotriene foam 0.005% in the treatment of plaque psoriasis francisco kerdel, md, faad;a christina don pa, mcmsc;b renata block pa-c, mms; caitlin lewis, phd;c rhonda schreiber msrnd conclusions methods resultsintroduction participants were asked “how satisfied are you with the improvement in psoriasis you’ve seen in the areas you have treated with calcipotriene foam, 0.005%?”. the responses from the final survey, after 8 weeks on therapy, are shown in the chart to the left. • patient satisfaction levels are strong across both genders and all ages with no significant difference in any one group. • satisfaction in the severity of psoriasis cohort increases as the bsa affected increases. • patients who treated their scalp only were most satisfied (85%), followed by those treating both the body and scalp (78%), and then body alone (70%). • patients who used the product as a monotherapy were more satisfied (79%) than those who used it in combination with other therapies (72%). affiliations and disclaimersreferences 1. gupta r, debbaneh mg, liao w, genetic epidemiology of psoriasis,. curr dermatol rep. 2014 march; 3(1):61-78. 2. stern rs, nijsten t, feldman sr, margolis dj, rolstad t. psoriasis is common, carries a substantial burden even when not extensive, and is associated with widespread treatment dissatisfaction. j investig dermatol symp proc. 2004 mar;9(2):136-9. 3. tan x, feldman sr, chang j, balkrishnan r. topical drug delivery systems in dermatology: a review of patient adherence issues. expert opin drug deliv. 2012 oct;9(10):1263-71. 4. stein gold lf. topical therapies for psoriasis: improving management strategies and patient adherence. semin cutan med surg. 2016 mar;35(2 suppl 2):s36-44; quiz s45. 5. del rosso jq, kircik lh, zeichner j, stein gold l. the clinical relevance and therapeutic benefit of established active ingredients incorporated into advanced foam vehicles: vehicle characteristics can influence and improve patient outcomes j drugs dermatol. 2019 feb 1;18(2s):s100-s107. 6. eastman wj, malahias s, delconte j, dibenedetti d. assessing attributes of topical vehicles for the treatment of acne, atopic dermatitis, and plaque psoriasis. cutis. 2014 jul;94(1):46-53. 7. feldman , s. r., mills, m., brundage, t., & eastman, w. j. (2013, march). a multicenter, randomized, double-blind study of the efficacy and safety of calcipotriene foam, 0.005%, vs vehicle foam in the treatment of plaque-type psoriasis of the scalp. jdd, 12(3), 300-306. 8. data on file, mayne pharma, inc. participant demographics 37 37 37 36 37 44 30 36 32 40 40 32 46 37 39 34 39 39 38 45 37 34 42 38 42 36 40 38 39 41 40 38 0 10 20 30 40 50 60 70 80 90 100 p e rc e n t o f r e sp o n d e n ts overall satisfaction at week 8 (n=276) very satisfied satisfied age severity of psoriasis location of use use of treatment 81% 74% 78% 72% 74% 74% 76% 80% 70% 85% 78% 79% 72% *% at the top of the bars = respondents who were either satisfied or very satisfied total respondents to week 8 survey n=276 n(%) gender male 102 (37) female 172 (62) other 2 (1) age 18-30 55 (20) 31-40 67 (24) 41-50 62 (22) 51-60 50 (18) 61+ 42 (15) race caucasian 221 (80) african american 14 (5) hispanic/latino 19(7) asian 11 (4) other 11 (4) severity of psoriasis %bsa less than 3% 110 (40) between 3-10% 121 (44) more than 11% 45 (16) location of treatment body only 134 (49) scalp only 71 (26) body and scalp 71 (26) use of treatment used alone 162 (59) used in combination 114 (41) gender • participants were asked “has your itch improved since starting calcipotriene foam, 0.005%? if yes, how improved?” • at week 8, 71% of participants reported an improvement in itch • 60% reported moderate or strong improvement. 29% 37% 23% 11% 71% perceived improvement in itch at week 8 (n=276) very improved moderately improved slightly improved 26 57 65 61 59 70 57 59 42 28 25 29 30 25 33 30 25 12 7 7 8 5 8 9 0 20 40 60 80 100 p e rc e n t o f r e sp o n d e n ts product attribute rating (n=276) excellent good fair 68% 85% 80% 91% 89% 95% 90% 89% *% at the top of the bars = sum of excellent and good yesno discussion 62 11 12 7 8 0 10 20 30 40 50 60 70 foam solution cream lotion ointment p e rc e n t o f r e sp o n d e n ts preferred treatment formulation (n=276) patients were invited to upload photographic evidence to illustrate their treatment progress over the 8 week period. this patient, a caucasian male, aged 62, was using calcipotriene foam, 0.005% on his body only, as a monotherapy. the reduction in visible plaque is clearly apparent. this patient was “very satisfied” at weeks 4 and 8. registration week 2 week 4 week 8 psoriasis is a common chronic immune-mediated inflammatory disease of the skin, with approximately 150,000 newly diagnosed patients in the united states each year.1 most patients report their disease has significant physical and psychosocial impact on their lives and non-adherence to topical psoriasis treatment has been correlated to patient perception of vehicle attributes and negative treatment outcomes.2-6 calcipotriene foam, 0.005% is the only steroid-free vitamin d3 analog approved for use in a foam vehicle and has proven safety and efficacy as a monotherapy.7 patient questionnaires administered during the calcipotriene foam, 0.005%, phase iii trials reported positive patient perceptions of the foam vehicle and therapeutic outcomes in psoriasis. these positive results in a controlled setting prompted a series of surveys to current users of calcipotriene foam, 0.005% to gather patient perspectives on its use in “real world” clinical practice. • a total of 276 participants completed the final survey at week 8 with diversity across gender, age, race, and severity of psoriasis. • the severity of patients’ psoriasis was described as % of body surface area (%bsa), where less than 3% can be considered mild, 3-10% moderate, and >11% as severe. • participants were also asked which areas of their body they were treating and whether they were using the product alone or in combination with other treatments. • participants were asked to rate a number of attributes of calcipotriene foam 0.005% in the 8 week survey and rated all very strongly. • when asked to rank the different topical formulations in order of preference, foam was clearly the most preferred option with 62% of participants ranking it number one. • the next most preferred formulation was cream (12%), then solution (11%). methods the completed surveys represent a significant sample size with diversity across gender, race and age. the foam formulation was preferred by the majority of participants, who rated all vehicle attributes very highly. patients perceived the treatment as effective and submitted photographic evidence to support this. overall calcipotriene foam, 0.005% was rated by patients as an effective and easy to use topical treatment for psoriasis. the results of these surveys support the phase iii clinical trial questionnaire results and point to a high likelihood for compliance with treatment regimens which include calcipotriene foam, 0.005%. 276 patients completed the final survey at week 8, with 76% either satisfied or very satisfied with the improvement in psoriasis they saw with the product. at week 8 the highest satisfaction rates were reported by the following subsets: those using calcipotriene foam, 0.005% on their scalp alone (85%), those with severe psoriasis (>11% bsa) (80%), and those using using the product as monotherapy (79%). satisfaction did not differ significantly by gender (76% for males and 75% for females) and no trend was seen across age groups (between 72-81%). additionally, after using the foam for 8 weeks, 73% of participants indicated they were likely or very likely to continue use of the product, and 79% indicated they would be likely or very likely to recommend the product to a friend or family member.8 all vehicle attributes rated highly and patients showed a very strong preference for the foam vehicle in comparison to other formulations. 76% 76% 75% a. dermatology residency program at the lecomt/larkin community hospital, palm springs campus, hialeah, florida; florida academic dermatology center, coral gables, florida; florida international university, miami, florida. b. florida academic dermatology center, coral gables, florida; c. clewy communications, raleigh, nc; d. mayne pharma, greenville, nc. these surveys and analysis were supported by mayne pharma. • patients with plaque psoriasis who were being treated with calcipotriene foam, 0.005%, were asked to rate their experiences using the product over the course of 8 weeks. • surveys were administered at registration and then weeks 2, 4 and 8 to gather feedback on patient satisfaction with the product, perceived improvement in symptoms and itch, vehicle attributes, and topical vehicle preference. • patients completed surveys within 3 days to ensure feedback was gathered at the specific time points. • patients were also invited to submit photographs to show their treatment progress. skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 185 short communications plant stellate trichomes: strange contaminants appearing in koh preparations lauren g. yi bs1, vernon j. forrester md2, michael p. timko phd3, barbara b. wilson md2 1university of virginia school of medicine, charlottesville, va 2department of dermatology, university of virginia, charlottesville, va 3department of biology, university of virginia, charlottesville, va we have observed stellate structures under microscopy on potassium hydroxide preparations of skin scrapings. these structures are starfish-shaped with three to eight legs joined in the center and are in whole or fragments (figure 1). although they are commonly observed on skin scrapings, their etiology and identity may be unknown to some dermatologists. cornelius and shelley reported similar findings in 1968.1 following careful examination of their possible biological origins, they concluded that these were fragments of plant trichomes, also known as stellate hairs, the unior multicellular outgrowths present on the epidermal surfaces of plant vegetative and floral organs.1 based on their morphological characteristics, cornelius and shelly proposed that the origin of the stellate trichomes in their preparations were from the undersurface of leaves of viburnum dentatum, or southern arrowwood.1 similarly, fleischer et al. (1994) identified arrowwood trichomes as nonpathogenic artifacts on skin preparations.2 interestingly, these structures have also been observed as contaminants in pap smears.3 given the long, tubular nature of the stellate trichome arms these structures may be mistaken for fungal hyphae or other fibrous material. for example, “floral-shaped fibers”, similar in morphology to the stellate structures we observed, were reported in skin samples from patients with morgellons disease and hypothesized by the authors to be keratin fibers produced by keratinocytes.4 figure 1. plant stellate trichome. typical appearance as seen on a potassium hydroxide preparation without skin scrapings (40x). skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 186 we suspected that these stellate structures were likely a contaminant from the air onto the slides rather than from the skin, and therefore performed potassium hydroxide preparations on slides without skin scrapings. the trichomes were found on multiple slides and were especially numerous (3-5 per slide) on slides that had been left on an open shelf for one week. this is not surprising since in addition to the viburnum species noted previously, stellate trichomes have been described in black oak, hibiscus, and members of the mallow family and can be found in a wide range of trees and herbaceous ornamentals including some plants commonly found in homes and offices. the purpose of this case is not only to remind dermatologists of the identity of this interesting appearing contaminant, but also to show that it is most likely coming from the environment and not from a patient’s skin scrapings. conflict of interest disclosures: none funding: none corresponding author: lauren g. yi, bs department of dermatology po box 800718 1221 lee st charlottesville, va 22908 phone: 434-924-5115 email: lgy8qu@virginia.edu references: 1. cornelius ce, shelley wb. a unique stellate plant hair on human skin: viburnum dentatum pubescence. arch dermatol. 1968;98:336-338. 2. fleischer ab, stonecipher m, kron ka, mordecai jj. microscopic artifact found during examination of the skin: plant hair of viburnum dentatum. cutis. 1994;54:37-39. 3. farkas ta. images in clinical medicine: arrowwood contaminant in pap smear. n engl j med. 2005;352:e20.4. 4. middelveen mj and stricker rb. filament formation associated with spirochetal infection: a comparative approach to morgellons disease. clin cosmet investig dermatol. 2011;4:167-177. mailto:lgy8qu@virginia.edu powerpoint presentation 0 20 40 60 80 100 5657 60 5556 63 404042 r e s p o n d e rs , % worst weekly pruritus nrs ≤3 0 20 40 60 80 100 7172 75 70 73 81 5657 61 r e s p o n d e rs , % dlqi ≤5 materials and methods patients and treatment • in ecztend, patients who completed pt of tralokinumab received open-label tralokinumab 300 mg every two weeks (q2w, home use) after a 600 mg loading dose plus optional topical corticosteroids (us class ≥4 or europe class ≤3) or topical calcineurin inhibitor, with visits every 8 weeks o all patients who completed pt at sites with ecztend were eligible to enroll in ecztend, regardless of prior treatment or response o for key inclusion and exclusion criteria, please see blauvelt et al3 • adult patients included in this post hoc analysis completed 56 weeks of open-label tralokinumab treatment in ecztend by the data cutoff (april 30, 2021) (figure 1a) • patients self-reported race at baseline of ecztend (figure 1b) • proportion of patients achieving easi-75/90, iga 0/1, easi≤7, worst weekly pruritus nrs≤ 3, and dlqi ≤ 5 were assessed. easi-75/90 determined relative to pt baseline • data are presented as observed. intermittent missing data are presented using last observation carried forward (locf). modified non-responder imputation (mnri) sets discontinuation from ecztend due to adverse event(s) or lack of efficacy as non-response and uses locf for other missing data • to account for potential baseline confounders with racial subgroup, logistic regression analysis adjusting for country, weight, easi, ethnicity and age (all at ecztend baseline) in addition to racial subgroup were conducted. estimated proportions from these analyses were expressed relative to us non-hispanic patients • data were used as per food and drug administration (fda) label and united states prescribing information (uspi) analyses asian n=203 black n=108 white n=1081 mean age, y (sd) 37.9 (13.9) 39.6 (13.4) 39.4 (14.1) male, n (%) 125 (61.6) 45 (41.7) 637 (58.9) ethnicity, n (%) hispanic or latino not hispanic or latino 2 (1.0) 201 (99.0) 5 (4.6) 103 (95.4) 79 (7.3) 1002 (92.7) country, n (%) united states, 49 (24.1) canada, 55 (27.1) germany, 2 (1.0) great britain, 9 (4.4) spain, 1 (0.5) france, 1 (0.5) japan, 86 (42.4) united states, 94 (87.0) canada, 7 (6.5) germany, 3 (2.8) great britain, 3 (2.8) france, 1 (0.9) united states, 187 (17.3) canada, 137 (12.7) poland, 178 (16.5) germany, 246 (22.8) great britain, 52 (4.8) spain, 123 (11.4) belgium, 62 (5.7) france, 61 (5.6) italy, 15 (1.4) czech republic, 20 (1.9) baseline scores parent trial ecztend parent trial ecztend parent trial ecztend iga, n (%) 3 4 89 (43.8) 114 (56.2) 51 (25.1) 14 (6.9) 73 (67.6) 35 (32.4) 22 (20.4) 7 (6.5) 575 (53.2) 506 (46.8) 308 (28.5) 63 (5.8) mean easi (sd) 32.5 (14.5) 9.2 (11.7) 27.9 (12.0) 6.9 (11.0) 30.7 (12.7) 8.6 (10.0) mean scorad score (sd) 70.0 (13.5) 33.5 (18.5) 65.3 (12.4) 27.6 (18.6) 69.2 (12.7) 33.5 (19.1) mean poem (sd), n 22.6 (4.7), 199 13.2 (6.8), 197 20.4 (6.2), 99 10.6 (7.2), 106 22.3 (5.1), 1037 12.4 (7.4), 1048 mean dlqi (sd), n 16.4 (6.9), 200 6.9 (5.8), 197 16.0 (7.7), 100 6.9 (6.4), 106 16.6 (6.9), 1041 6.7 (6.0), 1048 mean worst pruritus nrs (sd), n 7.9 (1.3), 180 5.3 (2.5), 202 8.0 (1.8), 63 4.6 (2.9) 7.6 (1.5), 971 4.9 (2.7), 1080 mean sleep interference nrs (sd), n 7.2 (1.9), 180 3.6 (2.8), 202 7.4 (2.2), 63 3.0 (3.1) 6.8 (2.0), 971 3.1 (2.8), 1080 efficacy and safety of up to two years of tralokinumab treatment in adults of different racial subgroups with moderate-to-severe atopic dermatitis tiffany mayo1, april armstrong2, leon kircik3, jonathan i. silverberg4, andrew blauvelt5, ben esdaile6, shannon schneider7, thomas mark8, melinda gooderham9, andrew f. alexis10 1university of alabama at birmingham, birmingham, al, usa; 2keck school of medicine of university of southern california, los angeles, ca, usa;3icahn school of medicine at mount sinai, new york, ny, usa; 4the george washington school of medicine and health sciences, washington, dc, usa; 5oregon medical research center, portland, or, usa; 6whittington health national health service foundation trust, london, uk; 7leo pharma inc., madison, nj, usa; 8leo pharma a/s, ballerup, denmark; 9skin centre for dermatology, peterborough, on, canada; 10weill cornell medicine, new york, ny, usa table 1. baseline demographic and disease characteristics of patients by racial subgroup table 2. summary of aes in ecztend by racial subgroup ain pts, worst pruritus nrs was assessed daily; in ecztend, worst pruritus nrs was assessed based on recall of the previous week before the visit. conclusions • improvements in disease severity, itch, and quality of life were comparable across different racial subgroups following up to two years of tralokinumab treatment in adults with moderate-to-severe ad • limitations of this analysis include the lack of a placebo arm in ecztend, disparate sample sizes across racial subgroups, and possible confounders not considered • the lower response rates observed for the asian subgroup relative to other racial subgroups could be partially explained by adjusting for country figure 1. schematic of (a) ecztend interim analysis of adult patients and (b) patient disposition at parent trial completion, ecztend baseline, and at april 30, 2021 data cutoff objective to evaluate the efficacy and safety of up to 2 years of tralokinumab treatment by self-identified racial subgroup (asian, black, white) in adults with moderate-to-severe ad results patients, demographics, and clinical characteristics • this post hoc analysis included 1392 adult patients who had completed 56 weeks of tralokinumab in ecztend (up to 2 years total) at data cutoff, april 30, 2021 and self-reported their race as asian, black, or white (figure 1b, table 1) o among patients who had completed 56 weeks of tralokinumab in ecztend at data cutoff, 24% had skin of color (self-reported race as asian, black, or other) o very few patients self-reported their race as other than asian, black, or white (n=38 patients total) and therefore were not included in this analysis • baseline demographic and disease characteristics were largely balanced across subgroups (table 1), although regional differences were present figure 2. proportion of patients by racial subgroup achieving easi-75, easi-90, iga 0/1, and easi≤7 at week 56 of ecztend references 1. weidinger s, novak n. lancet. 2016;387(10023):1109-1122. 2. kaufman b, et al. exp dermatol 2018; 27: 340-357. 3. blauvelt a, et al. j am acad dermatol. 2022;s0190-9622(22)02345-3. disclosures tiffany mayo has served as an investigator or consultant for eli lilly, chemocentryx, pfizer, janssen, galderma, bristol myers squibb, acelyrin, novartis, leo pharma, arcutis, and procter and gamble. april armstrong has served as a research investigator and/or scientific advisor to abbvie, almirall, arcutis, aslan, beiersdorf, bi, bms, epi, incyte, leo, ucb, janssen, lilly, nimbus, novartis, ortho dermatologics, sun, dermavant, dermira, sanofi, regeneron, pfizer, and modmed. leon kircik has served either as an investigator, consultant, or speaker for abbvie, almirall, amgen, arcutis, bausch health canada, bristol myers squibb, boehringer ingelheim, cellceutix, celgene, coherus, dermavant, dermira, eli lilly, leo, mc2, maruho, novartis, ortho dermatologics, pfizer, dr reddy's laboratories, sun pharma, ucb, taro, and xenoport. jonathan i silverberg reports honoraria as a consultant/advisory board member from leo pharma and has acted as a consultant for and/or received grants/honoraria from abbvie, anaptysbio, asana biosciences, galderma research and development, gsk, glenmark, kiniksa, leo pharma, lilly, medimmune, menlo therapeutics, pfizer, puricore, regeneron, and sanofi. andrew blauvelt has served as a speaker (received honoraria) for abbvie, arcutis, bristol-myers squibb, eli lilly and company, pfizer, regeneron, sanofi, and ucb, served as a scientific adviser (received honoraria) for abbvie, abcentra, affibody, aligos, almirall, alumis, amgen, anaptysbio, arcutis, arena, aslan, athenex, bluefin biomedicine, boehringer ingelheim, bristol-myers squibb, cara therapeutics, dermavant, ecor1, eli lilly and company, escient, evelo, evommune, forte, galderma, highlightii pharma, incyte, innoventbio, janssen, landos, leo, merck, novartis, pfizer, rapt, regeneron, sanofi genzyme, spherix global insights, sun pharma, tll pharmaceutical, trialspark, ucb pharma, vibliome, and xencor, and has acted as a clinical study investigator (institution has received clinical study funds) for abbvie, acelyrin, almirall, amgen, arcutis, athenex, boehringer ingelheim, bristol-myers squibb, concert, dermavant, eli lilly and company, evelo, evommune, galderma, incyte, janssen, leo, merck, novartis, pfizer, regeneron, sun pharma, and ucb pharma. ben esdaile has served either as an investigator, advisor or speaker for leo pharma, l’oréal, thornton & ross, bioderma, skin + me and abbvie. shannon schneider and thomas mark are employees of leo pharma. thomas mark owns leo pharma stock. melinda gooderham has been an investigator, speaker and/or advisor for: abbvie, amgen, akros, anaptysbio, aslan, arcutis, aristea, bausch health, bms, boehringer ingelheim, celgene, dermira, dermavant, eli lilly, galderma, gsk, incyte, janssen, kyowa kirin, leo pharma, medimmune, merck, meiji, moonlake, nimbus, novartis, pfizer, reistone, regeneron, roche, sanofi genzyme, sun pharma, and ucb. andrew f. alexis has received grants (funds to institution) from leo pharma, novartis, almirall, bristol myers squibb, amgen, vyne, galderma, valeant (bausch health), cara, arcutis, dermavant, abbvie, and castle; has served as an advisory board member or consultant for leo pharma, galderma, pfizer, sanofi-regeneron, dermavant, beiersdorf, ortho, l’oreal, bms, bausch health , ucb, vyne , arcutis, janssen, allergan, almirall, abbvie, sol-gel , amgen, visualdx, eli lilly, swiss american, and cutera; and a speaker for regeneron, sanofi-genzyme, pfizer, and bristol myers squibb. acknowledgements this analysis was sponsored by leo pharma a/s. medical writing according and editorial support from alphabet health by clair geary, phd was funded leo pharma a/s, ballerup, denmark, to good publication practice guidelines (https://www.ismpp.org/gpp3) introduction • atopic dermatitis (ad) is a chronic skin disease which may impact patients throughout their lifespan, requiring efficacious long-term treatment options with a favorable safety profile1 • although ad is highly prevalent in patients with skin of color, data on the efficacy of ad therapies in these patients is limited since most clinical trials enroll predominately white patients2 o several standard measures, including easi, can underestimate ad severity in dark skin2 • tralokinumab, a specific, high-affinity interleukin-13 inhibitor, is approved in europe, canada, and the united states for the treatment of adults with moderate-to-severe ad • ecztend (nct03587805) is an ongoing open-label extension trial assessing the safety and efficacy of tralokinumab over 5 years after the completion of parent trials (pt) the safety profile of up to 2 years of tralokinumab treatment was consistent across racial subgroups • through week 56 in ecztend, rates of adverse events (aes), serious aes, and aes leading to drug withdrawal were comparably low across racial subgroups (table 2) • the majority of aes in all subgroups were mild or moderate in severity and subjects recovered from most of the aes figure 3. percentage of patients achieving worst weekly pruritus nrs ≤3 and dlqi ≤5 by racial subgroup at week 56 of ecztend adjusting for differences in baseline characteristics and country between subgroups impacts estimated responder proportions • adjusted for race and country as main effects, easi-75 was achieved in 88% of asian patients, 90% of black patients, and 90% of white patients (figure 4) • similar patterns of estimated response were observed for iga 0/1 (figure 4) and when adjusting for region as main effect or the interaction between region and race figure 4. percentage of patients achieving easi-75 and iga 0/1 by racial subgroup before and after adjusting for baseline differences asian (n=203; pye=386.2) black (n=108; pye=169.7) white (n=1081; pye=1808.0) n (%) rate (ne/100 pye) n (%) rate (ne/100 pye) n (%) rate (ne/100 pye) all aes 162 (79.8) 167.8 71 (65.7) 142.6 850 (78.6) 208.2 severity mild 143 (70.4) 130.2 57 (52.8) 101.9 717 (66.3) 134.1 moderate 67 (33.0) 34.7 35 (32.4) 35.3 503 (46.5) 66.8 severe 10 (4.9) 2.8 7 (6.5) 5.3 80 (7.4) 7.4 serious aes 12 (5.9) 3.4 7 (6.5) 4.7 81 (7.5) 5.4 leading to withdrawal from trial 2 (1.0) 0.5 2 (1.9) 1.2 30 (2.8) 1.7 outcome not recovered/ not resolved 68 (33.5) 28.0 23 (21.3) 24.2 269 (24.9) 23.7 recovering/resolving 18 (8.9) 5.4 12 (11.1) 10.0 153 (14.2) 12.2 recovered/resolved 151 (74.4) 133.1 65 (57.4) 106.0 799 (73.9) 169.2 recovered/resolved with sequelae 1 (0.5) 0.3 3 (2.8) 1.8 16 (1.5) 1.0 unknown 3 (1.5) 1.0 1 (1.0) 0.6 28 (2.6) 1.9 scan to download a copy of this poster copies of this poster and its content, obtained through this qr code, are for personal use only and may not be reproduced without written permission from the authors abbreviations adj., adjusted; ae, adverse event; ad, atopic dermatitis; dlqi, dermatology life quality index; e, number of adverse events; easi, eczema area and severity index; iga, investigator’s global assessment; locf, last observation carried forward; mnri, modified non-responder imputation; n, number of patients achieving the indicated metric, or with ≥1 event; ne, number of events; n, number of patients with recorded observation; nrs, numerical rating scale; pye, patient-years of exposure; pt, parent trial; q2w, every 2 weeks; sd, standard deviation fall clinical dermatology conference, oct 20 – 23, 2022 comparable efficacy across racial subgroups with up to two years of tralokinumab treatment o worst weekly pruritus nrs ≤3 was achieved in 42% (71/169) of asian patients, 63% (48/76) of black patients, and 60% (458/765) of white patients, as observed (figure 3) o similar patterns of response were observed for easi-90, easi ≤7, iga 0/1, and dlqi ≤5, and when using locf or mnri to account for missing data (figures 2 and 3) • at week 56 in ecztend o easi-75 was achieved in 78% (130/167) of asian patients, 88% (66/75) of black patients and 83% (186/347) of white patients, as observed (figure 2) n 169 202 202 76 108 108 765 941 941 n 164 201 201 73 108 108 700 939 939 0 20 40 60 80 100 49 57 60 44 56 63 35 4042 r e s p o n d e rs , % worst weekly pruritus nrs ≤3 0 20 40 60 80 100 56 72 75 55 73 81 50 57 61 r e s p o n d e rs , % dlqi ≤5 asian mnri asian locf asian ao black ao black locf black mnri white ao white locf white mnri 0 20 40 60 80 100 7879 838283 88 7374 78 7879 838283 88 7374 78 r e s p o n d e rs , % easi-75 0 20 40 60 80 100 5859 646566 72 4647 51 r e s p o n d e rs , % easi-90 0 20 40 60 80 100 4950 53 6464 69 353537 r e s p o n d e rs , % iga 0/1 0 20 40 60 80 100 7677 818283 87 7071 74 r e s p o n d e rs , % easi ≤7 https://www.ismpp.org/gpp3 skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 939 short communication a rare case of early pregnancy-associated erythema annulare centrifugum in a low-resource setting erik jaklitsch, bs1, alicia mizes, md1,2, francisco sanchez, md3, ana romero, md3, katherin bonilla, ba3, alaina james, md, phd4 1 school of medicine, university of pittsburgh, pittsburgh, pa 2 memorial sloan kettering cancer center, new york city, ny 3 global brigades, tegucigalpa, honduras 4 department of dermatology, university of pittsburgh, pittsburgh, pa erythema annulare centrifugum (eac) is a reactive inflammatory dermatosis characterized by multiple, pruritic annular plaques that often resolve spontaneously.1 eac is putatively caused by hypersensitivity to medications, foods, infections, malignancies, stress, and arthropod bites; however, in many cases, a participating factor is not identified.2 we present a pregnant woman who was diagnosed with eac seen by our dermatology team during a short-term brigade in tegucigalpa, honduras. a healthy 28-year-old woman (gravida-1, para-1) presented to the urban clinic in tegucigalpa with a recurring pruritic rash of seven years. she first reported that the rash involved both hands, lower limbs, and thighs. at this time, she was diagnosed with allergic contact dermatitis from cleaning products and treated with topical steroids and antihistamines for 1 year without improvement. three years later, her symptoms worsened during her first pregnancy. her lesions had an annular shape, an expanding boarder, a clearing center and were pruritic. the wide differential diagnosis at this time included other reactive dermatoses like granuloma annulare, fungal infections like tinea corporis, and viral causes like pityriasis rosea. however, based on the characteristic physical features of the lesions, their variable distribution, their persistent recurrence, and a lack of concurrent systemic symptoms, she was diagnosed with eac. she received treatment with topical antifungals and topical steroids for six months without improvement. over the next three years, she experienced partial resolution and recurrence of the rash with no clear associated factors, until starting oral contraceptive pills (ocps) over the course of a month and experiencing worsening of the lesions. at that time, following a negative koh prep, she was prescribed clobetasol .05% for four months without improvement. she presented to our dermatology brigade with worsening pruritus and an increased number of scaly patches (figure 1). on physical examination, she had numerous (18cm) well-defined tan to pink annular patches with a peripheral, fine, white scale on her introduction case report skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 940 thighs, chest, and back. she denied changes in environmental factors or medications; therefore, a participating factor to cause rash flares was not identified, and an otherwise negative review of systems and lack of alarm symptoms decreased concern for other causes such as paraneoplastic processes. consequently, upon remembering that her lesions worsened prior to her first pregnancy, the patient took a pregnancy test which was positive despite one month of ocps. at 16 weeks, ultrasonographic confirmation of pregnancy dated conception to coincide with the month of eac recurrence and the patient elected not to pursue other treatment. this was the last time that the patient was seen and has not otherwise received any follow-up care at the practice. figure 1. a pink, annular 8 cm patch on the thigh with a peripheral, fine, white scale and central clearing upon presentation at the dermatology brigade in tegucigalpa, honduras. given the myriad causes that can contribute to its etiology, eac has been reported worldwide and is not thought to be specific to any particular geographic region. however, to the author’s knowledge this is the first reported case of eac in central america. this underscores the underrepresentation of dermatologic conditions in resource-limited settings, as well as the importance of the ability to recognize eac based on clinical findings alone and treat appropriately with limited options. treatment of an underlying causative agent, such as bacterial or fungal causes with appropriate antimicrobial therapy, can most directly alleviate manifestations of disease; in many cases such as ours, the cause may be idiopathic. therefore, topical or systemic corticosteroids can be used in mild/moderate and more severe/widespread cases, respectively, in order to reduce symptoms of inflammation and alleviate itching. oral antihistamines or immunosuppressants can also relieve pruritis and may be particularly useful if an allergic or autoimmune reaction is suspected. eac can therefore be managed in these low-resource settings based on availability of therapeutics and clinical presentation. while eac is more commonly associated with medications, infections, and allergies, associations with pregnancy that improve postpartum have been reported (table 1). a 21-year-old woman experienced asymptomatic eac of the trunk and extremities that resolved by week 4 of two consecutive pregnancies, abruptly reoccurred on the first day postpartum, and did not resolve for an additional three years.4 all other previously reported cases of eac suggest that lesion onset occurs between weeks 12-33 of pregnancy in a nulliparous woman with regression in the postpartum period.4 in contrast, our patient developed eac worsening during two pregnancies, with an earlier onset (weeks 1-4) and postpartum improvement. one proposed mechanism for the pathogenesis of eac is a delayed-type hypersensitivity reaction, in which an antigenic stimulus triggers an immune discussion skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 941 table 1. reported cases of eac associated with pregnancy and related patient history, disease presentation, and timeline. case age localization prior history of rash (y/n) onset of disease state resolution reappearance postpartum (y/n) author 1 28 arms, legs n week 32, pregnancy week 1, postpartum n rosina et al.7 2 34 legs n week 32, pregnancy week 1, postpartum n chiang et al.3 3 28 back, arms, legs n week 12, pregnancy week 36, pregnancy n dogan5 4 21 back, trunk, thighs, arms, legs y prior to first pregnancy week 4, pregnancy y ozkaya et al.4 5 28 abdomen, legs n week 26, pregnancy week 33, pregnancy n senel et al.8 6 28 back, chest, hands, arms, legs y *prior to both pregnancies and worsened at the start *diminished after both pregnancies and eventually resolved y jaklitsch et al. skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 942 response. this immune response involves t lymphocytes and cytokines, leading to local inflammation. the antigen responsible for initiating the immune response in eac is often unknown, but infection, environmental triggers, and immune dysregulation are all known to be instigating factors. prior studies have even suggested that human chorionic gonadotropin (hcg) may contribute to this response in pregnancy associated eac, since its production begins at implantation and peaks at week 12.5 in our case, increased levels of hcg or higher patient sensitivity immediately following implantation could have contributed to worsening symptoms in this novel early presentation. additionally, this dermatologic care relied on clinical acumen and patient history. in lowresource settings like honduras, biopsies are not standard of care due to high out-of-pocket costs and limited supplies. this report expands upon under-represented global skin disease in mainstream dermatology education, exemplifying care outside of resource-rich settings.6 conflict of interest disclosures: none funding: none corresponding author: erik jaklitsch, bs university of pittsburgh school of medicine pittsburgh, pa 15213 phone: (718) 755-2576 email: erj42@pitt.edu references: 1. white jw. gyrate erythema. dermatol clin. 1985 jan 1;3(1):129–39. 2. kim dh, lee jh, lee jy, park ym. erythema annulare centrifugum: analysis of associated diseases and clinical outcomes according to histopathologic classification. ann dermatol [internet]. 2016 apr 1 [cited 2022 apr 11];28(2):257. available from: /pmc/articles/pmc4828397/ 3. chiang ch, lai fj. pregnancy-associated erythema annulare centrifugum. j formos med assoc. 2015 jul;114(7):670–1. 4. ozkaya e, atcı t, erbudak dinc ee, elinc aslan ms. erythema annulare centrifugum: remission during two pregnancies and exacerbation in between. jddg j ger soc dermatology. 2017 nov;15(11):1136–8. 5. dogan g. pregnancy as a possible etiologic factor in erythema annulare centrifugum. am j clin dermatol. 2009 aug;10(1):33–5. 6. morrone a. poverty, dignity, and forgotten skin care: dermatology in the stream of human mobile population. dermatol clin [internet]. 2008 apr [cited 2022 aug 16];26(2):245–56. available from: https://pubmed.ncbi.nlm.nih.gov/18346556/ 7. rosina p, d’onghia fs, barba a. erythema annulare centrifugum and pregnancy. int j dermatol. 2002;41(8):516-517. doi:10.1046/j.1365-4362.2002.01552_5.x 8. senel e, gulec a. erythema annulare centrifugum in pregnancy. indian j dermatol. 2010;55(1):120. doi:10.4103/00195154.60371 winter clinical dermatology conference, hawaii (january 13–18, 2023) and miami (february 17–20, 2023) email: gerogina.long@sydney.edu.au conclusions • nivo significantly reduced the risk of recurrence by 58% compared with pbo in patients with resected stage iib or iic melanoma – hr, 0.42 (95% ci, 0.30-0.59; stratified p < 0.0001) – higher 12-month rfs rates of 89% vs 79% • benefit of nivo vs pbo was observed across prespecified subgroups, including t category and disease stage • clinically meaningful improvement in dmfs was observed with nivo vs pbo at this initial assessment (hr, 0.47; 95% ci, 0.30-0.72) • safety profile of nivo was consistent with previous reports and manageable using well-established treatment algorithms • these results support nivo as an effective adjuvant treatment option in resected stage iib or iic melanoma background • approximately one-third of patients with stage iib and half with stage iic disease experience recurrence within 5 years (figure 1)1 – prognosis of patients with stage iib and iic disease is similar to those with stage iiia and iiib melanoma, respectively,1-3 highlighting the need for effective and tolerable adjuvant therapies in this population • checkpoint inhibitors have transformed the adjuvant treatment of resected stage iii or iv melanoma4-8 • in keynote-716, adjuvant pembrolizumab vs placebo (pbo) in resected stage iib or iic melanoma improved recurrence-free survival (rfs): hazard ratio (hr), 0.65 (95% ci, 0.46–0.92)9 references 1. garbe c, et al. j clin oncol 2022;40:3741–3749. 2. garbe c, et al. j clin oncol 2020;38:2543–2551. 3. gershenwald je, et al. ca cancer j clin 2017;67:472–492. 4. eggermont amm, et al. lancet oncol 2015;16:522–530. 5. weber j, et al. n engl j med 2017;377:1824–1835. acknowledgments • the patients and families who have made this trial possible • the clinical study teams who participated • bristol myers squibb (princeton, nj) and ono pharmaceutical company, ltd. (osaka, japan) • this study was supported by bristol myers squibb • all authors contributed to and approved the presentation; writing and editorial assistance were provided by melissa kirk, phd, and michele salernitano of ashfield medcomms, an inizio company, funded by bristol myers squibb figure 1. recurrence risk of stage iib and iic disease aconfirmatory cohort. ajccv8, american joint committee on cancer, cancer staging manual, version 8; cmmr, central malignant melanoma registry; mss, melanoma-specific survival. adjuvant therapy with nivolumab versus placebo in patients with resected stage iib/c melanoma (checkmate 76k) georgina v. long,1 michele del vecchio,2 jeffrey weber,3 christoph hoeller,4 jean-jacques grob,5 peter mohr,6 stephan grabbe,7 caroline dutriaux,8 vanna chiarion-sileni,9 jacek mackiewicz,10 piotr rutkowski,11 petr arenberger,12 gaëlle quéreux,13 tarek meniawy,14 paolo a. ascierto,15 piyush durani,16 maurice lobo,16 federico campigotto,16 brian gastman,17* john m. kirkwood18* 1melanoma institute australia, the university of sydney, and royal north shore and mater hospitals, sydney, new south wales, australia; 2irccs istituto nazionale dei tumori, milan, italy; 3nyu langone medical center, new york, ny, usa; 4medizinische universität wien, vienna, austria; 5hôpital de latimone, marseille, france; 6elbe klinikum buxtehude, buxtehude, germany; 7university of mainz medical center, mainz, germany; 8hôpital saint andré, bordeaux, france; 9istituto oncologico veneto iov-irccs, padova, italy; 10institute of oncology, poznan university of medical sciences, poznan, poland; 11maria skłodowska-curie national research institute of oncology, warsaw, poland; 12charles university third faculty of medicine and university hospital of královské vinonrady, prague, czech republic; 13nantes university hospital, nantes, france; 14sir charles gairdner hospital, perth, australia; 15istituto nazionale tumori irccs fondazione pascale, naples, italy; 16bristol myers squibb, princeton, nj, usa; 17the cleveland clinic foundation, cleveland, oh, usa; 18upmc hillman cancer center, pittsburgh, pa, usa *contributed equally objective • the purpose of this report was to present the primary results of checkmate 76k evaluating nivolumab (nivo) vs pbo as adjuvant treatment in patients with resected stage iib or iic melanoma 87% 93%82% 83% 0 20 40 60 80 100 c 5-year risk of disease recurrencea (cmmr)1 stage iib stage iic 35% 43% 86% 80%77% 74% 0 20 40 60 80 100 iib iic iiia iiib iib iic iiia iiib m ss ( % ) m ss ( % ) 5-year mss ratea (cmmr)1,2 5-year mss rate (ajccv8)3 methods • in checkmate 76k (nct04099251), treatment-naive patients ≥ 12 years with completely resected stage iib or iic melanoma were randomized 2:1 to receive nivo or pbo as shown in figure 2 • the primary endpoint was investigator-assessed rfs (time between randomization and first recurrence) – recurrence events included the following: local, regional, or distant recurrence; new primary melanoma and melanoma in situ; death (due to any cause) – imaging assessments occurred every 26 weeks during years 1–3 and every 52 weeks in years 4 and 5 • key secondary endpoints were distant metastasis-free survival (dmfs; time between randomization and first distant recurrence or death) and safety • recurrence was investigator-assessed with imaging assessments approximately every 6 months in the first 3 years and annually in years 4 and 5 – tumor assessments were performed per contrast-enhanced computed tomography (ct) of the chest, abdomen, pelvis, and all other known and suspected sites of disease, unless known contraindications for ct intravenous contrast • the design of checkmate 76k includes an optional on-protocol nivo open-label portion following recurrence on either nivo (at ≥ 6 months from treatment) or pbo (at any time after recurrence) – the results presented here are from the initial blinded phase portion of the study • the interim rfs analysis was planned when approximately 123 rfs events occurred (80% information fraction); a final analysis is planned at approximately 154 events • the clinical cutoff for the interim analysis was june 28, 2022 – 135 rfs events (88% information fraction); 76.8% power and 0.678 critical hr • os is event driven and follow-up is ongoing figure 2. study design ffr, freedom from relapse (with censoring patients who died from causes other than disease); os, overall survival; pfs2, progression-free survival through next-line therapy. results patient population • a total of 790 patients were randomized (figure 3) – 39% of patients treated with nivo and 25% of pbo-treated patients discontinued treatment, most commonly due to study drug toxicity for nivo at 18% of patients and due to disease recurrence for pbo at 16% of patients • at a minimum overall study follow-up of 7.8 months, patients had a median follow-up of 15.8 months in the nivo arm and 15.9 months in the pbo arm • median number of doses received was 12 in the nivo arm and 13 in the pbo arm, with a mean (range) duration of treatment of 8.8 (0-12.1) and 9.9 (0-12.7) months, respectively • patient demographic and disease characteristics were well balanced, with 60% of the population being male and 40% at stage iic disease (table 1) – one-half of the patients had nodular melanoma subtype across arms blinded nivo/pbo treatment optional nivo openlabel (within ≤ 3 y) after recurrence ≥ 6 months posttreatment nivo or any time pbo nivo iv 480 mg q4w per patient eligibility and choice optional on-protocol open-label nivo treatment after first recurrence nivo iv 480 mg q4w for 12 months n = 526 pbo iv q4w for 12 months n = 264 stratify by t category r 2:1 primary endpoint • rfs by investigator secondary endpoints • os • safety • dmfs • pfs2 exploratory endpoints • ffr • treatment-free interval • quality of life treatment naive patients ≥ 12 y with • completely resected stage iib/c melanoma with standard wide local excision • negative sentinel lymph node biopsy n = 790 figure 3. patient treatment disposition atwo patients were not treated: 1 patient in itt no longer met study criteria and 1 classified as “other”. bseven patient discontinuations were related to covid: patient request (n = 1), death (n = 1), study drug toxicity (n = 2), unrelated ae (n = 3). ctwo patient discontinuations were related to covid: withdrew consent (n = 1) and death (n = 1). ae, adverse event; covid, coronavirus disease; itt, intention-to-treat. nivo • 526 itt • 524 safetya pbo • 264 itt • 264 safety 64 (12%) ongoing 257 (49%) completed 203 (39%) discontinuedb • 94 (18%) study drug toxicity • 29 (6%) patient request • 26 (5%) disease recurrence • 18 (3%) withdrew consent • 16 (3%) other • 11 (2%) unrelated ae • 6 (1%) death • 1 (< 1%) lost to follow-up • 1 (< 1%) maximum clinical benefit • 1 (< 1%) no longer met criteria 790 patients randomized 39 (15%) ongoing 158 (60%) completed 67 (25%) discontinuedc • 7 (3%) study drug toxicity • 0 patient request • 41 (16%) disease recurrence • 7 (3%) withdrew consent • 7 (3%) other • 1 (< 1%) unrelated ae • 2 (1%) death • 0 lost to follow-up • 2 (1%) maximum clinical benefit • 0 no longer met criteria table 1. patient baseline characteristics nivo (n = 526) pbo (n = 264) mean age, years (sd) 59.9 (13.9) 59.3 (13.6) male, n (%) 322 (61%) 161 (61%) ecog ps 0, n (%) 495 (94%) 245 (93%) stage, n (%) iib iic 316 (60%) 210 (40%) 163 (62%)a 101 (38%) t category, n (%) t3b t4a t4b 204 (39%) 112 (21%) 210 (40%) 104 (39%) 58 (22%) 102 (39%) melanoma subtype, n (%) nodular superficial spreading acral lentiginous other/not reported 266 (51%) 151 (29%) 28 (5%) 81 (15%)b 133 (50%) 82 (31%) 15 (6%) 34 (13%)c region, n (%) western europe us and canada australia eastern europe 303 (58%) 97 (18%) 68 (13%) 58 (11%) 160 (61%) 46 (17%) 30 (11%) 28 (11%) aone of these patients was incorrectly categorized as stage iib instead of iic. bcategorized as: desmoplastic melanoma (n = 21, 4%), lentigo maligna (n = 13, 2%), “other” (n = 44, 8%), and not reported (n = 3, 1%). ccategorized as: desmoplastic melanoma (n = 8, 3%), lentigo maligna (n = 3, 1%), “other” (n = 22, 8%), and not reported (n = 1, < 1%). • nivo significantly reduced the risk of recurrence vs pbo, with a stratified hr of 0.42 (95% ci, 0.30-0.59) and 12-month rfs rates of 89% vs 79% (figure 4) – overall, 13% of patients treated with nivo and 26% of pbo-treated patients experienced an rfs event (table 2) • rfs benefit was driven by reductions in the incidence of both distant recurrences (5% for nivo vs 12% for pbo) and regional recurrences (2% for nivo vs 8% for pbo) • new melanoma lesions occurred in 2% vs 3% of patients, respectively, and likely did not have an impact on the observed rfs benefit • the rfs forest plot shows that the rfs benefit with nivo was consistent across prespecified patient subgroups, which is illustrated by the clustering of hrs around the overall itt unstratified hr of 0.43 (table 3) – of particular interest, rfs benefit was consistent across t categories with an expected slightly overall worse prognosis for patients with t4b disease (figure 5) figure 4. primary endpoint: rfs na, not available; nr, not reached. 100 90 80 70 60 50 40 30 20 10 0 r f s (% ) 0 3 6 9 12 15 18 21 24 27 30 33 months 526 492 444 364 261 185 116 54 19 6 2 0 no. at risk nivo pbo 264 243 205 161 119 77 40 20 11 3 2 0 89% (95% ci, 86–92) 79% (95% ci, 74–84) nivo pbo nivo pbo events, n/n 66/526 69/264 median, mo (95% ci) nr (28.5–na) nr (21.6–na) stratified hr (95% ci) 0.42 (0.30–0.59) stratified, log rank p < 0.0001 table 2. patterns of first rfs events nivo (n = 526) pbo (n = 264) rfs events, n (%) recurrencea distant recurrence regional node recurrence local recurrence in-transit metastases new melanoma lesions new primary invasive melanoma melanoma in situ deaths prior to recurrence 66 (13%) 45 (9%) 26 (5%) 11 (2%) 8 (2%) 0 11 (2%) 4 (1%) 7 (1%) 10 (2%) 69 (26%) 58 (22%) 31 (12%) 20 (8%) 7 (3%) 0 8 (3%) 3 (1%) 5 (2%) 3 (1%) afor patients who had multiple recurrences that were identified on the same day, the most serious type is tabulated according to the displayed prespecified hierarchy. subgroup nivo n/n nivo 12-mo rfs rate, (95% ci) pbo n/n pbo 12-mo rfs rate, (95% ci) unstratified hr (95% ci)a unstratified hra (95% ci) overallb overall 66 (526) 89.0 (85.6–91.6) 69 (264) 79.4 (73.5–84.1) 0.43 (0.31–0.61) age category i < 65 years 33 (305) 91.5 (87.4–94.4) 39 (155) 81.2 (73.5–86.9) 0.40 (0.25–0.64) ≥ 65 years 33 (221) 85.4 (79.3–89.8) 30 (109) 76.8 (66.8–84.2) 0.48 (0.29–0.78) age category ii ≥ 18–< 65 33 (305) 91.5 (87.4–94.4) 39 (155) 81.2 (73.5–86.9) 0.40 (0.25–0.64) ≥ 64–< 75 16 (140) 89.2 (81.9–93.6) 18 (77) 79.7 (67.9–87.5) 0.45 (0.23–0.88) ≥ 75–< 85 17 (77) 78.2 (65.6–86.6) 11 (30) 68.4 (46.1–83.0) 0.46 (0.21–0.99) ≥ 85 0 (4) na 1 (2) 100.0 (100.0–100.0) — sex male 39 (322) 89.9 (85.6–93.0) 51 (161) 76.5 (68.6–82.7) 0.33 (0.22–0.51) female 27 (204) 87.6 (81.6–91.7) 18 (103) 83.9 (74.1–90.2) 0.71 (0.39–1.29) disease stage iib 26 (316) 92.6 (88.6–95.2) 36 (163) 84.1 (76.8–89.3) 0.34 (0.20–0.56) iic 40 (210) 83.8 (77.5–88.4) 33 (101) 72.0 (61.6–80.0) 0.51 (0.32–0.81) t category t3b 16 (204) 92.6 (87.2–95.7) 22 (104) 83.4 (73.8–89.7) 0.36 (0.19–0.68) t4a 10 (112) 92.6 (85.1–96.4) 14 (58) 85.2 (70.7–92.8) 0.27 (0.12–0.63) t4b 40 (210) 83.8 (77.5–88.4) 33 (102) 72.3 (61.9–80.2) 0.52 (0.33–0.82) region us and canada 8 (97) 92.7 (84.2–96.7) 8 (46) 84.2 (67.8–92.7) — western europe 41 (303) 89.0 (84.5–92.3) 46 (160) 78.0 (70.0–84.0) 0.40 (0.26–0.61) eastern europe 8 (58) 84.5 (71.3–92.0) 9 (28) 80.2 (58.6–91.3) — australia 9 (68) 87.9 (76.2–94.1) 6 (30) 78.8 (58.7–89.9) — table 3. rfs by subgroup with unstratified hr aper statistical analysis plan, hr is not computed for subset categories with less than 10 events per treatment group. bstratified rfs is 0.42 (0.30–0.59). favors nivo favors pbo 0.125 1 80.25 0.5 2 4 figure 6. secondary endpoint: dmfs • in a descriptive analysis, the benefit of nivo for reducing the risk of distant metastases or death was similar to the overall rfs benefit (figure 6) – hr was 0.47 (95% ci, 0.30-0.72) with 12-month dmfs rates of 92% for nivo and 87% for pbo • the safety profile of nivo was similar to the known anti–pd-1 monotherapy profile observed across many trials • grade 3-4 treatment-related adverse events (traes) were 10% in the nivo group and 2% in the placebo group and any grade trae leading to discontinuation was 15% vs 3% (table 4) – there was 1 treatment-related death (0.2% of patients) with nivo due to heart failure and acute kidney injury that was not related to myocarditis • as expected, the most common trae was fatigue, which occurred at a similar incidence in the nivo and pbo arms (figure 7) – the most frequent grade 3-4 traes in the nivo arm were diarrhea, rash, and increased alanine aminotransferase (alt), aspartate aminotransferase (ast), and blood creatine phosphokinase, all at 1% each • the only grade 3-4 immune-mediated ae in more than 1% of patients treated with nivo was hepatitis at 3% (table 5) figure 5. subgroup analysis of rfs: t category aunstratified. table 4. safety summary ae, n (%) nivo (n = 524) pbo (n = 264) any grade grade 3-4 any grade grade 3-4 any ae 502 (96%) 115 (22%)a 229 (87%) 32 (12%)a trae 433 (83%) 54 (10%) 142 (54%) 6 (2%) immune-mediated ae 213 (41%) 41 (8%) 45 (17%) 3 (1%) any ae leading to discontinuation 91 (17%) 37 (7%) 9 (3%) 2 (1%) trae leading to discontinuation 77 (15%) 29 (6%) 7 (3%) 2 (1%) ain addition, there was 1 grade 5 event in each treatment group, considered unrelated to study treatment, myocardial ischemia for nivo and “sudden death” for pbo. figure 7. traes in ≥ 5% patients in the nivo group 6. weber j, et al. presented at the society for melanoma research (smr) international congress; october 28–31, 2021; virtual. 7. eggermont, amm, et al. n engl j med 2018;378:1789–1801. 8. eggermont amm, et al. lancet oncol 2021;22:643–554. 9. luke jj, et al. lancet 2022;399:1718–1729. table 5. immune-mediated aes by categorya ae, n (%) nivo (n = 524) pbo (n = 264) any grade grade 3-4 any grade grade 3-4 non-endocrine immune-mediated aes where immune-modulating medication was initiated rash 45 (9%) 4 (1%) 4 (2%) 0 diarrhea/colitis 24 (5%) 6 (1%) 2 (1%) 1 (< 1%) hepatitis 22 (4%) 14 (3%) 1 (< 1%) 0 hypersensitivity 7 (1%) 0 0 0 pneumonitis 4 (1%) 1 (< 1%) 2 (1%) 0 nephritis and renal dysfunction 3 (1%) 2 (< 1%) 1 (< 1%) 0 endocrine immune-mediated aes regardless of immune-modulating medication initiation hypothyroidism 60 (11%) 0 0 0 adrenal insufficiency 12 (2%) 3 (1%) 3 (1%) 0 hyperthyroidism 40 (8%) 1 (< 1%) 4 (2%) 0 hypophysitis 9 (2%) 5 (1%) 2 (1%) 0 thyroiditis 6 (1%) 0 0 0 diabetes (type i) 3 (1%) 3 (1%) 0 0 aimmune-mediated aes, reported between the first dose and 100 days after the last dose of study therapy, included both non-endocrine events requiring immune-modulating medication and endocrine events, regardless of treatment and not requiring specific laboratory criteria. nivolumab placebo grade 3-4 1-2 25 20 15 10 5 0 fatigue pruritus diarrhea rash arthralgia h ypothyroidism asthenia dry m outh h yperthyroidism nausea increased alt increased ast increased blood creatine phosphokinase infusionrelated m aculopapular rash m yalgia 106 53 97 25n = 80 25 57 18 54 15 54 0 38 18 36 7 36 3 39 7 33 13 30 6 30 13 27 2 25 5 28 14 20% 20% 19% 9% 15% 9% 11% 7% 10% 6% 10% 0 7% 7% 7% 3% 7% 1% 7% 3% 6% 5% 6% 2% 6% 5% 5% 1% 5% 2% 5% 5% in ci d e n ce ( % ) traes, n (%) nivo (n = 524) pbo (n = 264) any 433 (83%) 142 (54%) grade 3–4 54 (10%) 6 (2%) 100 90 80 70 60 50 40 30 20 10 0 d m f s (% ) nivo pbo 0 3 6 9 12 15 18 21 24 27 30 33 months 92% (95% ci, 89–94) 87% (95% ci, 81–90) 526 506 461 381 273 194 122 55 20 7 2 0 no. at risk nivo pbo 264 252 215 177 130 89 49 26 15 3 2 0 nivo pbo events, n/n 42/526 41/264 median, mo (95% ci) nr (28.5–na) nr stratified hr (95% ci) 0.47 (0.30–0.72) nivo pbo events, n/n 10/112 14/58 median, mo (95% ci) 28.5 (28.5–na) 23.6 (15.7–na) hr (95% ci)a 0.27 (0.12–0.63) 0 3 6 9 12 15 112 100 90 80 70 60 50 40 30 20 10 0 r f s (% ) months no. at risk nivo pbo 3318 58 21 24 27 30 109 53 98 44 82 35 57 23 41 15 26 8 14 5 5 2 2 0 1 0 0 0 93% (95% ci, 85–96) 85% (95% ci, 71–93) nivo pbo t4a nivo pbo events, n/n 16/204 22/104 median, mo (95% ci) nr nr (18.4–na) hr (95% ci)a 0.36 (0.19–0.68) 0 3 6 9 12 15 204 93% (95% ci, 87–96)100 90 80 70 60 50 40 30 20 10 0 r f s (% ) months no. at risk nivo pbo 3318 104 83% (95% ci, 74–90) 21 24 27 30 187 101 166 84 136 69 99 54 79 36 47 21 17 6 10 4 2 2 1 1 0 0 nivo pbo t3b 0 3 6 9 12 15 210 100 90 80 70 60 50 40 30 20 10 0 r f s (% ) months no. at risk nivo pbo 3318 102 21 24 27 30 196 89 180 77 146 57 105 42 65 26 43 11 23 9 4 5 2 1 0 1 0 0 84% (95% ci, 78–88) 72% (95% ci, 62–80) nivo pbo t4b nivo pbo events, n/n 40/210 33/102 median, mo (95% ci) nr (23.7–na) nr (16.0–na) hr (95% ci)a 0.52 (0.33–0.82) these data were previously presented at the society for melanoma research (smr) international congress; october 17–20, 2022; edinburgh, united kingdom. mailto:gerogina.long@sydney.edu.au microsoft word september 2020 comp 862 proof.docx skin september 2020 volume 4 issue 5 copyright 2020 the national society for cutaneous medicine 481 compelling comments delusions of parasitosis influenced by crowdsourcing diagnostic platform crowdmed julian stashower, ba1, katherine belote, md1, barrett zlotoff, md1 1university of virginia school of medicine, charlottesville, virginia a distraught 48-year-old female presented to our clinic with signs and symptoms consistent with delusions of parasitosis. physical exam showed geometric, bilateral, superficial excoriations with overlying crust and scattered hypopigmented macules on the chest, abdomen, back, buttocks, and upper and lower extremities, with sparing of the face and interscapular back. an already challenging patient encounter was made even more difficult when the patient claimed that she had identified the source of her discomfort. she explained that with the help of paid, non-physician users on the website crowdmed, she had discovered that parasites were living underneath her skin. crowdmed is a popular subscription-based crowdsourcing platform that reports having dealt with thousands of patients. websites such as crowdmed can provide opportunities for patient education and facilitate the spread of knowledge. however, when used inappropriately, crowdsourcing websites like crowdmed can put strain on doctor-patient relationships. patients on crowdmed distribute cash awards to contributors that they feel helped the most, which may motivate contributors not to provide correct information, but information that patients will like. additionally, nearly half of all active individuals who offer patients advice on crowdmed have no medical affiliation of any kind.1 this is concerning for both patients and providers alike as the information being given may not be medically accurate or provided by credible sources. the stress and confusion caused by receiving conflicting opinions from crowdsourcing websites and dermatology practices could lead to physician mistrust, especially since patients may not readily discard paid-for medical advice. with thousands of patients now looking to crowdsourcing websites such as crowdmed for medical guidance, we feel it is important that clinicians be aware that they exist and query patients about their use. equipped with this information, providers can prepare to counsel patients that report having consulted a crowdsourcing website prior to their visit. in our case, we were able to forge a therapeutic alliance with the patient by utilizing an approach described in the literature by drs. abstract thousands of patients look to crowdsourcing websites such as crowdmed for medical guidance. these websites can provide opportunities for patient education and facilitate the spread of knowledge. however, when used inappropriately, crowdsourcing websites like crowdmed can put strain on doctorpatient relationships. we present a case that highlights how a patient’s delusions of parasitosis were influenced and supported by the crowdsourcing website crowdmed. skin september 2020 volume 4 issue 5 copyright 2020 the national society for cutaneous medicine 482 viraat patel and john koo and will consider initiation of pimozide or risperidone if necessary and appropriate.2 conflict of interest disclosures: none funding: none corresponding author: julian stashower, ba university of virginia school of medicine 1215 lee street charlottesville ,va 22908 phone: 703-673-8741 fax: 434-244-4504 email: jas2wf@virginia.edu references: 1. meyer and, longhurst ca, singh h. crowdsourcing diagnosis for patients with undiagnosed illnesses: an evaluation of crowdmed. j med internet res. 2016;18(1). doi:10.2196/jmir.4887 2. patel v, koo jym. delusions of parasitosis; suggested dialogue between dermatologist and patient. journal of dermatological treatment. 2015;26(5):456-460. doi:10.3109/09546634.2014.996513 skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 936 short communication halo nevi after covid-19 vaccination: molecular mimicry attributed cutaneous side-effect? kelly e. owens, bs1, jeffery t. kwock, md2, matilda w. nicholas, md, phd2 1 school of medicine, duke university, durham, nc 2 department of dermatology, duke university, durham, nc although well tolerated, covid-19 vaccination is associated with several cutaneous adverse reactions such as injection site reactions, urticaria and less commonly erythema multiforme, subacute cutaneous lupus erythematosus, pityriasis rosea, and vitiligo.1,2 to date, there has been one report of halo nevi appearing after covid-19 vaccination. here, we document a second case of a young man who developed numerous halo nevi at sites of pre-existing nevi following covid-19 vaccination. fifteen months prior to presentation to clinic, a healthy 21-year-old male received the johnson & johnson (j&j) covid-19 vaccine. three months later, the patient noticed a change in his pre-existing moles—a ring of “vitiligo” now surrounded each mole. eight months after receiving the j&j covid-19 vaccine, the patient received the moderna booster and subsequently contracted covid19 two months later. despite these added exposures, he did not notice any further change in his moles. abstract covid-19 vaccination is a crucial component of the public health response to reduce the spread of covid-19. although well-tolerated, covid-19 vaccination is associated with several cutaneous adverse reactions. here, we document a case of a young man who developed numerous halo nevi at sites of pre-existing nevi following covid-19 vaccination. our patient is a 21-year-old male who presented to clinic after noticing a recent change in his moles. three months after receiving the johnson & johnson (j&j) covid-19 vaccine, the patient reported that he developed a ring of “vitiligo” surrounding each of his existing moles. he also received the moderna covid-19 booster 8 months after receiving the j&j vaccine and contracted covid-19 two months later, with no additional change in his moles. the patient was otherwise well with no past medical or family medical history of skin cancer. on examination, the patient was found to have numerous halo nevi that had developed at sites of pre-existing nevi and were distributed over his face, neck, trunk, and extremities. examination of his scalp revealed patches of white hair, underneath which were additional halo nevi. the development of vitiligo in the setting of covid-19 vaccination is thought to be related to the activation of autoimmunity. autoimmunity secondary to covid-19 vaccination may be the cause of this patient’s halo nevi, given the patient’s age and absence of any systemic symptoms. introduction case report skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 937 figure 1. (a) regular, brown nevi surrounded by an ovoid, circumferential area of hypopigmentation, consistent with halo nevi, located on patient’s left upper back. some areas of hypopigmentation without a central mole were also noted. (b) halo nevi on left scalp with overlying hypopigmented hair. (c) numerous halo nevi on right cheek and neck. hypopigmented section of hair overlying halo nevi on right scalp. fifteen months after first receiving the j&j covid-19 vaccine, the patient presented to clinic and underwent a full body skin exam. numerous regular, brown macules with a surrounding halo of hypopigmentation were noted on the trunk and upper extremities. examination of his scalp revealed patches of white hair which overlaid further halo nevi. on dermoscopy, the halo nevi were normal in size, symmetric with regular borders, and had no significant color variation. the patient denied any accompanying itching, burning, pain, or bleeding. he had no past medical or family medical history of skin cancer. the patient did report a history of blistering sunburns but denied a history of tanning bed use. he had no known allergies or outpatient medications. the patient denied fever, chills, weight loss, night sweats, joint pain, headaches, nausea, vomiting, or bleeding problems. the patient was assured that his nevi were benign and was scheduled to return to clinic in 6 months for a follow-up evaluation of the halo nevi. halo nevi typically progress through four stages, starting with the development of hypopigmentation surrounding the nevus and ultimately resulting in the loss of the original nevus and return of hypopigmentation to previous skin tone. vitiligo and a paraneoplastic phenomenon have previously been associated with halo nevi, often prompting closer investigation.3 given our patient’s age, lack of concerning features on dermoscopy, timeline of presentation, and absence of any systemic symptoms, we found it unlikely that his halo nevi were neoplastic in origin. rather, autoimmunity discussion a b c skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 938 secondary to covid-19 vaccination may have been the cause of his halo nevi. covid-19 vaccination is known to elicit a powerful humoral and cellular immune response.4 numerous case reports detailing an exacerbation or new-onset of vitiligo after covid-19 vaccination have been published since early 2021. although the etiology of halo nevi is not fully understood, it is thought that vitiligo and halo nevi share a common feature: destruction of melanocytes by cytotoxic t cells; therefore, it is possible that the occurrence of halo nevi and vitiligo after covid-19 vaccination stems from a similar pathophysiology.5 several theories have been proposed on the mechanism surrounding covid-19 vaccination and autoimmune skin reactions. one prominent theory is molecular mimicry, where cross reactivity of t or b cells between the adenovirus vector and melanocytes causes hypopigmentation. with increased tcell, b-cell, antibody, interferon, and interleukin production after vaccination, it is plausible that melanocytes could become an accidental target of this robust immune response.4 in fact, a study in 2020 found that sars-cov-2 antibodies had a moderate to strong reaction with 21 out of 50 human tissue antigens, including transglutaminase 2 and 3, collagen, myelin basic protein, and thyroid peroxidase.6 to conclude, more research is needed to understand the intricacies of new onset halo nevi and vitiligo after covid-19 vaccination. conflict of interest disclosures: none funding: none corresponding author: kelly owens, bs duke university school of medicine durham, nc email: kelly.owens@duke.edu references: 1. avallone g, quaglino p, cavallo f, et al. sars-cov-2 vaccine-related cutaneous manifestations: a systematic review. int j dermatol. oct 2022;61(10):1187-1204. doi:10.1111/ijd.16063 2. gambichler t, boms s, susok l, et al. cutaneous findings following covid-19 vaccination: review of world literature and own experience. j eur acad dermatol venereol. feb 2022;36(2):172-180. doi:10.1111/jdv.17744 3. nedelcu r, dobre a, brinzea a, et al. current challenges in deciphering sutton neviliterature review and personal experience. j pers med. sep 9 2021;11(9)doi:10.3390/jpm11090904 4. sadoff j, le gars m, shukarev g, et al. interim results of a phase 1-2a trial of ad26.cov2.s covid-19 vaccine. n engl j med. may 13 2021;384(19):1824-1835. doi:10.1056/nejmoa2034201 5. yang y, li s, zhu g, et al. a similar local immune and oxidative stress phenotype in vitiligo and halo nevus. j dermatol sci. jul 2017;87(1):50-59. doi:10.1016/j.jdermsci.2017.03.008 6. vojdani a, kharrazian d. potential antigenic cross-reactivity between sars-cov-2 and human tissue with a possible link to an increase in autoimmune diseases. clinical immunology. 2020;217108480. doi:10.1016/j.clim.2020.108480 acknowledgements: medical writing support was provided by prescott medical communications group (chicago, il) with financial support from ortho dermatologics | presented at the fall clinical dermatology conference • october 17-20, 2019 • las vegas, nv synopsis ◾ quality of life (qol) in patients with acne has been shown to correlate more strongly with patient-reported severity than physician-reported severity, suggesting that patient perception may be important to consider during acne treatment1 ◾ in acne patients, the psychosocial impacts are greater compared with other dermatologic conditions, particularly with feelings of despair and distress2 ◾ the first lotion formulation of tretinoin was developed by utilizing novel polymeric emulsion technology to provide an important alternative option to treat acne patients3 ◾ in two phase 3 studies (nct02932306, nct02965456), tretinoin 0.05% lotion was shown to be highly effective and well tolerated in patients with moderate-to-severe acne4 objective ◾ to evaluate if improvements in qol with tretinoin 0.05% were correlated with improvements in acne symptoms methods ◾ qol data from two multicenter, randomized, double-blind, vehicle-controlled studies were pooled in this post hoc analysis ◾ participants with moderate or severe acne were randomized (1:1) to receive tretinoin 0.05% lotion or vehicle, once-daily for 12 weeks ◾ in these studies, cerave® hydrating cleanser and cerave® moisturizing lotion (l’oreal, ny) were provided as needed for optimal moisturization/cleaning of the skin ◾ qol was assessed using the validated acne-qol questionnaire in 4 different domains: self-perception, social, emotional, and acne symptoms • the correlation between the acne symptom domain (which represents the severity of acne) and the other three domains was assessed • higher scores for each domain reflect improved health-related qol, with the acne symptom domain score correlating inversely with acne severity (ie, higher score = improvement in acne symptoms) results ◾ the pooled population included 1640 participants (tretinoin, n=819; vehicle, n=821), 909 (55.4%) of whom were female; participants’ ages ranged from 9 to 58 years ◾ mean changes from baseline to week 12 in acne-qol domain scores indicated greater improvements with tretinoin 0.05% vs vehicle: self-perception (7.4 vs 6.7); role-emotional (6.8 vs 6.0); role-social (4.8 vs 4.6); and acne symptoms (6.5 vs 5.6) ◾ there was a significant correlation between improvements in acne symptoms and the other 3 qol domains at baseline and at week 12 (p<0.001) • the correlation between the acne symptom scores and the other domains was similar at baseline, with a pearson’s correlation of 0.69 for self-perception (figure 1) and role-emotional (figure 2) and 0.68 for role-social (figure 3) • at week 12, correlations were similar (0.66, 0.67, and 0.61, respectively) with clear improvements seen with tretinoin treatment (figures 1, 2, and 3 [higher scores for each domain vs baseline]) figure 1: correlation between acne symptoms and self-perception at baseline and week 12 in patients treated with tretinoin 0.05% lotion (itt population; pooled data) 5 4 3 2 1 0 6 5 4 3 2 1 0 6 s e lf -p e rc e p ti o n ( a ve ra g e s co re ) im p ro ve m e n t 0 1 2 3 4 5 6 acne symptoms (average score) improvement a. baseline s e lf -p e rc e p ti o n ( a ve ra g e s co re ) im p ro ve m e n t 0 1 2 3 4 5 6 acne symptoms (average score) improvement b. week 12 correlation=0.69 correlation=0.66 higher scores for each domain reflect improved health-related qol. itt, intent-to-treat. figure 2: correlation between acne symptoms and role-emotional at baseline and week 12 in patients treated with tretinoin 0.05% lotion (itt population; pooled data) 5 4 3 2 1 0 6 5 4 3 2 1 0 6 r o le -e m o ti o n a l (a ve ra g e s co re ) im p ro ve m e n t 0 1 2 3 4 5 6 acne symptoms (average score) improvement a. baseline r o le -e m o ti o n a l (a ve ra g e s co re ) im p ro ve m e n t 0 1 2 3 4 5 6 acne symptoms (average score) improvement b. week 12 correlation=0.69 correlation=0.67 higher scores for each domain reflect improved health-related qol. itt, intent-to-treat. figure 3: correlation between acne symptoms and role-social at baseline and week 12 in patients treated with tretinoin 0.05% lotion (itt population; pooled data) 5 4 3 2 1 0 6 5 4 3 2 1 0 6 r o le -s o ci a l (a ve ra g e s co re ) im p ro ve m e n t 0 1 2 3 4 5 6 acne symptoms (average score) improvement a. baseline r o le -s o ci a l (a ve ra g e s co re ) im p ro ve m e n t 0 1 2 3 4 5 6 acne symptoms (average score) improvement b. week 12 correlation=0.68 correlation=0.61 higher scores for each domain reflect improved health-related qol. itt, intent-to-treat. conclusions ◾ improvements in acne symptoms scores correlated with improvements in the other qol domains; these correlations were observed following 12 weeks of treatment with tretinoin 0.05% lotion ◾ these findings suggest the improvements seen in acne symptoms are associated with improvements in other measures of qol references 1. martin ar, et al. clin exp dermatol. 2001;26(5):380-385. 2. gorelick j, et al. j dermatol nurses assoc. 2015;7(3):154-162. 3. kircik lh, et al. j drugs dermatol. 2019;18(4):s148-154. 4. tyring sk, et al. j drugs dermatol. 2018;17(10):1084-1091. author disclosures dr. heather woolery-lloyd is a shareholder for somabella laboratories, llc. she has served as a speaker for aclaris and ortho dermatologics, consultant for ortho dermatologics, and received grants/research funding from allergan, galderma, nestle, pfizer, endo, leo pharma, eirion, golgel, and aclaris. dr. julie harper has received honoraria from aclaris, almirall, biopharmx, cassiopea, cutanea, dermira, foamix, galderma, laroche-posay, ortho dermatologics, and sun. dr. eric guenin is an employee of ortho dermatologics. acne-related quality of life: correlation between acne symptom scores and other domains following treatment with tretinoin 0.05% lotion heather c woolery-lloyd, md1; julie c harper, md2; eric guenin, pharmd, phd, mph3 1department of dermatology and cutaneous surgery, university of miami miller school of medicine, miami, fl; 2dermatology & skin care center of birmingham, birmingham, al; 3ortho dermatologics, bridgewater, nj 101102042_cobi_pop_pk_l1a presented at the winter clinical dermatology conference; january 13-18, 2023; kohala coast, hawaii copies of this poster obtained through this qr code, are for your personal use only and may not be reproduced without permission from the authors. copyright © 2023. all rights reserved. background • the long-term, relapsing-remitting nature of atopic dermatitis (ad) often requires flexibility in treatment, such as dose reduction and treatment interruption1 • the jade regimen trial (nct03627767), which included patients with moderate-to-severe ad, was conducted to evaluate maintenance of response to the janus kinase 1 (jak) inhibitor abrocitinib with continuous dosing, reduced dose, or withdrawal of abrocitinib2 – patients who stopped responding (experienced flare) during the maintenance period received rescue treatment objective • to evaluate the efficacy and safety of rescue therapy in jade regimen methods patients • jade regimen was a multicenter, double-blind, responder-enriched, placebo-controlled, phase 3, randomized-withdrawal study (figure 1) – the induction period consisted of 12 weeks of treatment with abrocitinib 200 mg by mouth once daily – patients who responded to induction (achieved investigator’s global assessment [iga] score of 0/1 with ≥2-point reduction from baseline and ≥75% improvement in eczema area and severity index [easi] response) were randomly assigned to dose continuation, dose reduction, or withdrawal of abrocitinib for 40 weeks (maintenance period) – patients who experienced flare during the maintenance period (ie, lost ≥50% of week 12 easi response and had a new iga score ≥2) received rescue therapy (abrocitinib 200 mg + topical medicated treatment) for 12 weeks figure 1. jade regimen study design randomization of respondersc 1:1:1 n=798 end of treatment end of study open-label induction period 40-week maintenance treatment period follow-up period day 1 week 52 week +4week 12 screening: 28 days medicated topical washout period: 3 days placebo qd (n=267) abrocitinib 200 mg qd (n=266) abrocitinib 100 mg qd (n=265)abrocitinib 200 mg qdn=1233 12-week rescue treatment period for patients experiencing flarea abrocitinib 200 mg qd + topical therapyb qd, once daily. aflare was defined as ≥50% loss of easi response at randomization and iga score ≥2. b topical therapy was permitted only during the rescue period and included topical corticosteroids, calcineurin inhibitors (tacrolimus or pimecrolimus), and phosphodiesterase 4 inhibitors (crisaborole) when required per local standard of care. cresponder criteria at week 12 are defined as iga score 0/1 with ≥2-point reduction from baseline and ≥75% improvement from baseline in easi response. patients • eligible patients were aged ≥12 years, had moderate-to-severe ad (iga score ≥3; easi score ≥16; percentage of body surface area [%bsa] affected ≥10; peak pruritus numerical rating scale [pp-nrs; used with permission from regeneron pharmaceuticals inc. and sanofi score ≥4) for ≥1 year, and had inadequate response or intolerance to topical medication or required systemic therapy to control ad analysis • recaptured iga, easi, and pp-nrs responses, defined as scores not worse than responses at randomization baseline in patients who received rescue therapy, were assessed at all scheduled time points during the rescue period • safety was assessed through adverse events (aes) results efficacy • in the abrocitinib 200-mg, abrocitinib 100-mg, and placebo arms, 43 (16.2%), 104 (39.2%), and 204 (76.4%) patients, respectively, entered the rescue period after experiencing protocol-defined flare • by week 12 of the rescue period, 74%, 57%, and 68% patients who had been randomly assigned to undergo withdrawal of abrocitinib (ie, placebo) were able to recapture their iga, easi, and pp-nrs responses, respectively (figures 2a-c) • among patients who were randomly assigned to receive abrocitinib 200 mg, recapture rates were 36% (iga), 33% (easi), and 29% (pp-nrs); the corresponding rates among those who had received abrocitinib 100 mg were 51%, 32%, and 40%, respectively (figures 2a-c) figure 2. proportions of patients who recaptured (a) iga, (b) easi, and (c) pp-nrs responsesa with rescue therapy after experiencing protocol-defined flareb 100 0 2 4 8 120 20 40 60 80 51.4 68.2 71.6 68.2 31.9 40.9 41.2 39.7 38.7 41.4 27.6 28.6 c p at ie nt s, % (9 5% c i) time, weeks evaluable patients, n placebo abrocitinib 100 mg qd abrocitinib 200 mg qd 157 88 29 169 85 29 173 94 31 88 58 21 abrocitinib 200 mg � placebo abrocitinib 200 mg � abrocitinib 100 mg abrocitinib 200 mg � abrocitinib 200 mg 100 0 2 4 8 120 20 40 60 80 19.8 44.9 50.7 57.1 8.0 25.0 30.7 32.0 7.3 17.5 22.0 33.3 b p at ie nt s, % (9 5% c i) time, weeks evaluable patients, n placebo abrocitinib 100 mg qd abrocitinib 200 mg qd 198 100 40 203 101 41 192 100 41 196 103 42 100 0 2 4 8 120 20 40 60 80 26.0 58.1 67.0 74.0 20.0 42.0 45.5 50.5 17.1 22.5 31.7 35.7 a p at ie nt s, % (9 5% c i) time, weeks evaluable patients, n placebo abrocitinib 100 mg qd abrocitinib 200 mg qd 198 100 40 203 101 41 192 100 41 196 103 42 easi, eczema area and severity index; iga, investigator’s global assessment; pp-nrs, peak pruritus numerical rating scale; qd, once daily. ªrecapture of response was defined as a score not worse than the score at randomization baseline. bflare was defined as ≥50% loss of week 12 easi response and iga score ≥2. safety • aes were experienced by a greater proportion of patients who entered the rescue period from the abrocitinib 200-mg treatment arm (55.8%) than from the placebo arm (33.8%) or the abrocitinib 100-mg arm (30.8%) (table 1) – most aes in the rescue period were mild or moderate across treatment arms table 1. summary of adverse events during the rescue period of jade regimen abrocitinib 200 mg  placebo n=204 abrocitinib 200 mg  abrocitinib 100 mg n=104 abrocitinib 200 mg  abrocitinib 200 mg n=43 any ae, n (%) 69 (33.8) 32 (30.8) 24 (55.8) severe ae, n (%) 4 (2.0) 2 (1.9) 2 (4.7) discontinuation because of ae, n (%) 2 (1.0) 3 (2.9) 2 (4.7) most frequently reported teae of any cause (>5% in any treatment group), n (%) nasopharyngitis 8 (3.9) 6 (5.8) 3 (7.0) upper respiratory tract infection 17 (8.3) 2 (1.9) 2 (4.7) dermatitis atopic 7 (3.4) 4 (3.8) 3 (7.0) teaes of special interest herpes zoster 2 (1.0) 4 (3.8) 2 (4.7) thrombocytopenia 0 0 0 ae, adverse event; teae, treatment-emergent adverse event. conclusion • rescue therapy with abrocitinib 200 mg + topical medicated therapy recaptured response in a large proportion of patients who experienced flare during the maintenance period of jade regimen and was associated with an acceptable safety profile references 1. boguniewicz m et al. ann allergy asthma immunol. 2018;120:10-22. 2. blauvelt a et al. j am acad dermatol. 2022;86:104-112. acknowledgments editorial/medical writing support under the guidance of the authors was provided by megan elder, phd, at apothecom, san francisco, ca, usa, and was funded by pfizer inc., new york, ny, usa, in accordance with good publication practice (gpp 2022) guidelines (ann intern med. 2022;10.7326/m22-1460). this study was funded by pfizer inc. previously presented at the american academy of allergy, asthma & immunology (aaaai) annual meeting; february 25-28, 2022; phoenix, arizona. efficacy of abrocitinib rescue therapy in the phase 3 study jade regimen jonathan i. silverberg,1 mark boguniewicz,2 kim papp,3 athanasios tsianakas,4 pinaki biswas,5 claire feeney,6 mark levenberg7 1the george washington university school of medicine and health sciences, washington, dc, usa; 2national jewish health and university of colorado school of medicine, denver, co, usa; 3k. papp clinical research and probity medical research, waterloo, on, canada; 4fachklinik bad bentheim, bad bentheim, germany; 5pfizer inc., new york, ny, usa; 6pfizer ltd., surrey, united kingdom; 7pfizer inc., collegeville, pa, usa disclosures jis served as an investigator for celgene, eli lilly and company, f. hoffmann-la roche, menlo therapeutics, realm therapeutics, regeneron, and sanofi; as a consultant for pfizer inc., abbvie, anacor, anaptysbio, arena pharmaceuticals, dermavant, dermira, eli lilly and company, galderma, glaxosmithkline, glenmark, incyte, kiniksa pharmaceuticals, leo pharma, menlo therapeutics, novartis, realm therapeutics, regeneron, and sanofi-genzyme; and as a speaker for regeneron and sanofi-genzyme. mb has been an investigator for regeneron and incyte and advisor for pfizer inc., abbvie, eli lilly and company, incyte, janssen, leo pharma, regeneron, and sanofi-genzyme. kp has been a consultant, scientific adviser, investigator, scientific officer, and/or speaker for pfizer inc., abbvie, akros, allergan, amgen, anacor, arcutis, astellas, astrazeneca, baxalta, baxter, bausch health, boehringer ingelheim, bms, canfite, celgene, coherus, dermira, dow pharma, eli lilly and company, forward pharma, galderma, genentech, gilead, glaxosmithkline, janssen, kyowa hakka kirin, leo pharma, medimmune, meiji seika pharma, merck sharp & dahme, merck-serano, mitsubishi pharma, novartis, prcl research, regeneron, roche, sanofi-aventis/genzyme, sun pharma, takeda, ucb, and valeant. at had nothing to declare pk, cf, and ml are employees and stockholders of pfizer inc. skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 106 in-depth reviews biologic prescribing patterns among mount sinai psoriasis patients: results of a retrospective chart review alexa choy,1 jonathan vebman,1 christopher j. yao, mph1,2 1department of dermatology, icahn school of medicine at mount sinai, new york, ny 2university of rochester school of medicine and dentistry, rochester, ny psoriasis is a painful and chronic inflammatory skin condition that can be disabling to both the physical and psychological health of affected patients.1 in 2013, it was reported psoriasis was prevalent in 7.4 million adults in the united introduction introduction: psoriasis is a painful and chronic inflammatory skin condition that not only impacts the quality of life of patients but is also a socioeconomic burden due to the cost of treatment, particularly with biologic treatments. objective: the purpose of the study is to understand biologic prescribing patterns among mount sinai psoriasis patients and assess its relationship to insurance policy, which may limit treatment access. methods: this study reviewed randomized, de-identified charts of psoriasis patients in a nine-physician academic practice at mount sinai (new york, united states) with the following insurers: aetna, blue cross blue shield, empire blue cross blue shield, medicare a&b, and united healthcare, treated with the following biologics: secukinumab, etanercept, adalimumab, infliximab, brodalumab, ustekinumab, ixekizumab and guselkumab. a chisquare test was performed to compare prescribed biologics by insurance company. results: ustekinumab was the most prescribed biologic treatment across all the insurance plans. there were also disproportionate prescriptions of certain biologics for patients under particular insurance plans. etanercept, brodalumab, and infliximab were the least prescribed biologics. conclusion: results highlight certain patterns in the prescribed biologics of mount sinai patients. prescribed biologics tend to vary by different insurers. however, ustekinumab was the most frequently prescribed biologic among all insurers, though it is not the most efficacious biologic based on pasi responses. future research should be conducted to assess how differences in insurance policies (e.g. cost to patient) affect biologic prescribing. abstract skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 107 states.2 psoriasis is also associated with an increased risk of comorbidities, such as psoriatic arthritis, crohn’s disease, malignancy, psychological/mental illness, obesity and cardiovascular diseases.3 there is also a significant socioeconomic burden in the cost of psoriasis and its treatments.1 among u.s. adults, 32.1% of those with restricted prescription medication, experienced a prominent decline in their health status.4 psoriasis currently has no cure and, therefore, requires extensive and long-term treatment.1 though a common and effective treatment for psoriasis, biologic therapies have higher costs, compared to other psoriasis treatments, such as phototherapy and traditional systematic treatments.10 there are also differences in efficacy among the biologics. a recent network meta-analysis showed brodalumab was significantly more efficacious than secukinumab, ustekinumab and etanercept based on pasi responses after 52 weeks.11 however, little information concerning insurance policy and access to biologics is known. one recent survey in ulcerative colitis found that 219 (43.8%) of surveyed gastroenterologists experienced limitations to prescribing biologics. two of the most commonly cited prescribing barriers included patient insurance restrictions (79.0%) and out-of-pocket costs (71.7%).12 thus, the purpose of this study is to understand biologic prescribing patterns among mount sinai psoriasis patients and assess its relationship to insurance policy, which may limit treatment access. chart review this retrospective study was conducted on randomized de-identified charts of psoriasis patients from the medical electronic billing database, epic, at the mount sinai dermatology department faculty practice, from nine different dermatologists. the charts were dated from december 5, 2016 through june 25, 2018. the conducted review collected charts of psoriasis patients with the highest frequency insurance plans at mount sinai’s dermatology department: aetna, blue cross blue shield (bc/bs), empire blue cross blue shield (empire bc/bs), medicare a&b and united healthcare, treated with the following biologic treatments: ustekinumab, guselkumab, adalimumab, secukinumab, ixekizumab, etanercept, brodalumab and infliximab. data were collected on patient’s sex, age, zip code, insurance company and prescribed biologic. statistical analysis statistical analyses were conducted with stata version 15.1 (statacorp llc, college station, tx, usa). first, we generated demographic statistics (age, sex, residence) for patients with each insurance company. a contingency table chi-square test was performed for patients with the insurance plans aetna, bc/bs, empire bc/bs, medicare a&b, and united healthcare and prescribed either adalimumab, ustekinumab or guselkumab. secukinumab, etanercept, infliximab, brodalumab and ixekizumab were omitted from this contingency table chisquare test because fewer than 5 patients had these combinations: empire bc/bs with secukinumab, bc/bs with etanercept, empire bcbs with etanercept, aetna with infliximab, empire bc/bs with infliximab, medicare a&b with infliximab, aetna with brodalumab, bc/bs with brodalumab, empire bc/bs with brodalumab, united healthcare with brodalumab, bc/bs with ixekizumab and empire bc/bs with ixekizumab. methods skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 108 patient sample the study cohort included 210 unique patients with 579 prescriptions for a biologic treatment from their dermatologists (table 1). ninety-three patients (44.3%) were female and 117 (55.7%) were male. seventy-four patients (35.2%) resided in manhattan, 28 (13.3%) in new jersey and 27 (12.9%) in brooklyn, while the remaining 81 patients (38.6%) resided in the greater new york area or other regions of the united states. the mean age (standard deviation) was 53.0 (19.3) with the majority (21.4%) within the age range 61-70. biologics prescribed for patients on different insurance plans overall, ustekinumab was the most commonly prescribed biologic (n=276 [47.7%]) (table 2). ustekinumab was also the most frequently prescribed biologic for each individual insurance plan: aetna (52.0%), bc/bs (61.5%), empire bc/bs (34.7%), medicare a&b (43.9%) and united healthcare (44.1%) (table 2). there was also a disproportionate amount of prescriptions for particular biologic treatments for some insurers. of the empire bc/bs patients, there were 24.5% adalimumab and 26.5% guselkumab prescriptions; only 8.2% secukinumab, 4.1% ixekizumab and 2.0% infliximab prescriptions, and no prescriptions for brodalumab. for united healthcare patients, 22.1% of patients were prescribed secukinumab, compared to fewer than 10% of prescriptions for other biologics. infliximab, brodalumab and etanercept were the least prescribed biologics at the respective frequencies: 12 (2.1%), 17 (2.9%) and 26 (4.5%) (table 2). for patients with aetna, bc/bs, empire bc/bs, medicare a&b and united healthcare and prescribed either ustekinumab, guselkumab or adalimumab, there was a significant difference between the number of patients with the insurance plans and their biologic prescription (p<0.001). table 1. descriptive statistics of analyzed patients (n=210). variable frequency (%) sex female 93 (44.3) male 117 (55.7) age (mean ± sd) 54.0 ± 19.3 age ranges 11-20 6 (2.9) 21-30 19 (9.1) 31-40 43 (20.5) 41-50 22 (10.5) 51-60 28 (13.3) 61-70 45 (21.4) 71-80 30 (14.3) 81-90 16 (7.6) 90-100 1 (0.5) region by zip code manhattan 74 (35.2) new jersey 28 (13.3) brooklyn 27 (12.9) other 81 (38.6) results skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 109 table 2. frequency (%) of biologics prescribed for patients on different insurance plans* insurance companies studies were: aetna, blue cross blue shield (bc/bs), empire blue cross blue shield (empire bc/bs), medicare a&b and united healthcare with the biologics: ustekinumab, guselkumab, adalimumab, secukinumab, ixekizumab, etanercept, brodalumab and infliximab. the contingency table chi-square test for performed for patients with the insurance plans aetna, bc/bs, empire bc/bs, medicare a&b and united healthcare and prescribed either ustekinumab, guselkumab or adalimumab was statistically significant, indicating there is a difference between number of patients with the aforementioned insurance plans and their biologic prescription (p<0.001). *specific insurance information for each plan was not available to reference specific policies for biologic access. high number of prescriptions though this study originally intended to identify prescribing patterns among different insurers, the most significant outcome was identifying ustekinumab as the most frequently prescribed biologic among all insurers and within the entire cohort. interestingly, ustekinumab is not as effective as some other biologics. for instance, yao and lebwohl (2019) analyzed the time of onset of antipsoriatic drugs, including popular, available biologics for psoriasis.5 that study analyzed two outcomes: time for 25% of patients to achieve a 75% improvement from baseline pasi (pasi 75) and time for patients to achieve a mean 50% improvement from baseline pasi (pasi 50). ustekinumab performed slower than brodalumab, ixekizumab, secukinumab, infliximab, and adalimumab in both study outcomes. additionally, results from a longterm (52 week) efficacy meta-analysis of biologic pasi responses also determined brodalumab and secukinumab both responded with higher proportions of pasi 75, pasi 90 and pasi 100 than ustekinumab.11 though ustekinumab is a less efficacious biologic treatment compared to some of the other common antipsoriatic biologics, it is the most frequently prescribed within this study cohort. at mount sinai, because ustekinumab is only prescribed every 3 months, it is administered during the patients’ office visit and therefore qualifies as a medical benefit. because most patients have co-insurance, with supplementary insurance to pay their copayments, their ininsurance company (%) biologic aetna bc/bs empire bc/bs medicare united total ustekinumab 64 (52.0) 56 (61.5) 17 (34.7) 83 (43.9) 56 (44.1) 276 (47.7) guselkumab 19 (15.5) 7 (7.7) 13 (26.5) 23 (12.2) 11 (8.7) 73 (12.6) adalimumab 9 (7.3) 8 (8.8) 12 (24.5) 16 (8.5) 9 (7.1) 54 (9.3) secukinumab 7 (5.7) 9 (9.9) 4 (8.2) 22 (11.6) 28 (22.1) 70 (12.1) ixekizumab 13 (10.6) 4 (4.4) 2 (4.1) 24 (12.7) 8 (6.3) 51 (8.8) etanercept 8 (6.5) 0 (0.0) 0 (0.0) 10 (5.3) 8 (6.3) 26 (4.5) brodalumab 3 (2.4) 1 (1.1) 0 (0.0) 10 (5.3) 3 (2.4) 17 (2.9) infliximab 0 (0.0) 6 (6.6) 1 (2.0) 1 (0.5) 4 (3.2) 12 (2.1) total (%) 123 (100.0) 91 (100.0) 49 (100.0) 189 (100.0) 127 (100.0) 579 (100.0) discussion skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 110 office treatments are covered as part of the office visit and therefore the patient has no out-of-pocket expenses. however, the other biologics are considered a pharmacy benefit because they are self-administered; therefore, the patient must pay a copayment out-of-pocket every time their prescription is renewed. thus, because ustekinumab may end up being less costly for the patient due to these insurance policies, doctors may choose to prescribe it more often. low number of prescriptions the low number of prescriptions for infliximab, brodalumab and etanercept was also examined. although specific reasons for biologic selection was not identified in the charts, potential explanations are plausible. infliximab is given by infusion and therefore may be unfavorable to dermatologists. it is also plausible brodalumab is not often prescribed by dermatologists because of the package insert stating brodalumab is associated with suicidal ideations.6 etanercept was likely limited in prescriptions because of its lower efficacy relative to other agents. low and high doses of etanercept are the slowest acting antipsoriatic biologics compared to secukinumab, etanercept, adalimumab, infliximab, brodalumab, ustekinumab, and ixekizumab, making it the least effective of the all the biologics in this study.5 limitations there are limitations to this study. data only included mount sinai patients and were therefore not representative of other hospitals or regions. mount sinai dermatology faculty practice also does not include medicaid patients, who are seen in the resident clinic; therefore, the results of the study do not factor in the medicaid population. it is also not definitive whether a dermatologist prescribed a certain drug due to insurance coverage restrictions or for other reasons. for example, pre-existing, chronic co-morbidities could be a determining factor for why a patient would be prescribed a particular biologic (and not necessarily the most efficacious biologic).9 another factor is ixekizumab was only approved on december 1, 2017,7 and guselkumab was only approved on july 13, 2017,8 which may have skewed the number of ixekizumab and guselkumab prescriptions to a lower frequency because the study collected charts that began on december 5th, 2016. nonetheless, although ixekizumab and guselkumab were approved last, the number of prescriptions for these two treatments still surpass those of infliximab, brodalumab and etanercept. data on compliance were not collected, which may influence clinical outcomes or biologic treatment preference. we were also unable to obtain information regarding the tiering system of each insurance company, which would have provided information about how each individual insurer affects choice in biologic. also, data were not collected on any fees charged by mount sinai for injections or subcutaneous injection training. lastly, some patients may have had a copayment assistance program, in which the drug company would have covered any pharmacy benefit out-of-pocket expenses, thus, newer biologics could be obtained for very little costs. insurance company coverage would, in turn, not have affected the patient’s prescription. the results of our study highlight certain patterns and discrepancies among biologic prescriptions for mount sinai psoriasis patients. though prescribed biologics vary among insurers, ustekinumab was the most conclusion skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 111 frequently prescribed biologic among all insurers, though it is not the most efficacious based on pasi responses. future research should be conducted to assess how differences in insurance policies (e.g. cost to patient) affect biologic prescribing. conflict of interest disclosures: none funding: none corresponding author: christopher j. yao, mph university of rochester school of medicine and dentistry, 601 elmwood avenue, box 62, rochester, ny, 14642 phone: 917-817-2241 email: chrisyao@sas.upenn.edu references: 1. world health organization. global report on psoriasis. (2016). world health organization website. http://apps.who.int/iris/bitstream/handle/10665/20 4417/9789241565189_eng.pdf?sequence=1. 2. rachakonda, t. d., schupp, c. w., & armstrong, a. w. (2014). psoriasis prevalence among adults in the united states. j am acad dermatol, 70(3), 512-516. 3. kaushik, s. b., & lebwohl, m. g. (2019). psoriasis: which therapy for which patient psoriasis comorbidities and preferred systemic agents. j am acad dermatol, 80(1), 27-40 4. heisler, m., langa, k. m., eby, e. l., fendrick, a. m., kabeto, m. u., & piette, j. d. (2004). the health effects of restricting prescription medication use because of cost [pdf]. med care, 42(7), 626-634. 5. yao, c. j., & lebwohl, m. g. (2019). onset of action of antipsoriatic drugs for moderate-tosevere plaque psoriasis: an update. j drugs dermatol: jdd, 18(3), 229-233. 6. food and drug administration. siliq risk evaluation and mitigation strategy (rems). https://www.accessdata.fda.gov/drugsatfda_docs /rems/siliq_2017-06-08_full.pdf. (publication no. 4109073). (2017, june). 7. doolen, j. national psoriasis foundation. fda approves taltz for psoriatic arthritis. national psoriasis foundation website. https://www.psoriasis.org/advance/fda-approvestaltz-psoriatic-arthritis. (2017, december 1). 8. national psoriasis foundation. fda approves biologic tremfya for psoriasis. national psoriasis foundation website. https://www.psoriasis.org/advance/fda-approvesbiologic-tremfya-psoriasis. (2017, july 13). 9. kaushik, s. b., & lebwohl, m. g. (2019). cme part ii psoriasis: which therapy for which patient focus on special populations and chronic infections. j am acad dermatol, 80(1), 43-53. 10. nelson, a. a., pearce, d. j., fleischer, a. b., jr., balkrishnan, r., & feldman, s. r. (2008). costeffectiveness of biologic treatments for psoriasis based on subjective and objective efficacy measures assessed over a 12-week treatment period. j am acad dermatol, 58(1), 125-135. 11. sawyer, l. m., cornic, l., levin, l. a., gibbons, c., moller, a. h., & jemec, g. b. (2019). long-term efficacy of novel therapies in moderate-to-severe plaque psoriasis: a systematic review and network meta-analysis of pasi response. j eur acad dermatol venereol, 33, 355-366. 12. lasch k, liu s, ursos l, et al. gastroenterologists’ perceptions regarding ulcerative colitis and its management: results from a large-scale survey. adv ther. 2016;33:1715–1727. mailto:chrisyao@sas.upenn.edu http://apps.who.int/iris/bitstream/handle/10665/204417/9789241565189_eng.pdf?sequence=1 http://apps.who.int/iris/bitstream/handle/10665/204417/9789241565189_eng.pdf?sequence=1 https://www.accessdata.fda.gov/drugsatfda_docs/rems/siliq_2017-06-08_full.pdf https://www.accessdata.fda.gov/drugsatfda_docs/rems/siliq_2017-06-08_full.pdf https://www.psoriasis.org/advance/fda-approves-taltz-psoriatic-arthritis https://www.psoriasis.org/advance/fda-approves-taltz-psoriatic-arthritis https://www.psoriasis.org/advance/fda-approves-biologic-tremfya-psoriasis https://www.psoriasis.org/advance/fda-approves-biologic-tremfya-psoriasis background ■ itch affects 60–90% of patients with psoriasis; it may be severe, with a significant negative impact on health-related quality of life (hr-qol)1–4 – itch can negatively affect physical activity, sleep, and psychological well-being ■ in the multinational assessment of psoriasis and psoriatic arthritis (mapp) survey that included 1,005 us patients, many patients reported itch as the most important factor contributing to disease severity; however, physicians generally considered itch to be less important5 ■ tapinarof (vtama®; dermavant sciences, inc.) is a first-in-class, non-steroidal, topical, aryl hydrocarbon receptor (ahr) agonist approved by the food and drug administration for the treatment of plaque psoriasis in adults,6 and under investigation for the treatment of psoriasis in children down to 2 years of age and for atopic dermatitis in adults and children down to 2 years of age – tapinarof cream 1% once daily (qd) demonstrated statistically significant efficacy versus vehicle and was well tolerated in adults with mild to severe plaque psoriasis in two 12-week, pivotal phase 3 trials, psoaring 1 (nct03956355) and psoaring 2 (nct03983980)7 ■ several patient-reported methods of assessing the impact of itch were utilized in the pivotal trials: – the peak pruritus numeric rating scale (pp-nrs) measures maximal itch symptoms, scored on an 11-point scale, where 0=no itch and 10=worst imaginable itch8 – the dermatology life quality index (dlqi) is a 10-item questionnaire that evaluates the impact of psoriasis symptoms on qol; itch item 1 (evaluating itch, soreness, painfulness, or stinging) is scored on a 4-point scale rating the impact of itch on qol, where 0=not at all and 3=very much9 – the psoriasis symptom diary (psd) assesses the severity, bother, and functional impact of psoriasis symptoms; items 1 (itching severity) and 2 (bothered by itching) are rated on an 11-point scale, where 0=absent and 10=worst imaginable10 objective ■ to present patient-reported itch outcomes from the psoaring 1 and psoaring 2 clinical trials methods trial design ■ adults with mild to severe plaque psoriasis enrolled in psoaring 1 or psoaring 2 were randomized 2:1 to tapinarof 1% qd or vehicle qd for 12 weeks (figure 1) figure 1. psoaring 1 and 2 trial design adults with mild to severe plaque psoriasis • aged 18–75 years • pga score ≥2* • bsa ≥3% to ≤20% double-blind treatment (12 weeks) 2:1 2:1 tapinarof 1% qd (n=340) tapinarof 1% qd (n=343) vehicle qd (n=170) vehicle qd (n=172) (n=510) (n=515) r r *pga of 2 (mild) or 4 (severe) was limited to ~10% each of the total randomized population; ~80% of the randomized population had a pga of 3 (moderate). bsa, body surface area; pga, physician global assessment; qd, once daily; r, randomized. endpoints and statistical analysis ■ the proportion of patients achieving a pp-nrs score of 0 or 1, indicating an itch-free state, was compared between treatment groups at baseline and weeks 2, 4, 8, and 12 using the cochran-mantel-haenszel analysis stratified by baseline physician global assessment (pga) score ■ pp-nrs total score and psd items 1 and 2 scores were assessed for improvement from baseline at weeks 2, 4, 8, and 12 ■ dlqi item 1 score was assessed for improvement from baseline at weeks 4 and 12 ■ continuous variables were analyzed using an analysis of covariance, with randomized treatment as a factor, baseline pga score as a covariate, and baseline value as a continuous covariate – treatment effect is presented as a least squares mean difference results baseline patient demographics and disease characteristics ■ the analyses included 683 tapinarof-treated and 342 vehicle-treated patients (table 1) – mean pp-nrs, dlqi, and psd total scores and psd items 1 and 2 scores were similar across treatment groups in psoaring 1 and 2 table 1. baseline patient demographics and disease characteristics psoaring 1 psoaring 2 tapinarof 1% qd (n=340) vehicle qd (n=170) tapinarof 1% qd (n=343) vehicle qd (n=172) age, years, mean (sd) 49.8 (13.7) 49.1 (13.3) 50.0 (13.1) 50.0 (13.7) male, n (%) 213 (62.6) 86 (50.6) 188 (54.8) 102 (59.3) weight, kg, mean (sd) 91.7 (24.6) 92.8 (22.7) 92.9 (24.3) 89.6 (19.9) bmi, kg/m2, mean (sd) 31.4 (7.8) 32.5 (7.6) 31.8 (7.7) 30.7 (6.3) pp-nrs total score, mean (sd) 5.7 (2.9) 6.1 (2.8) 5.9 (2.7) 6.1 (2.8)   score of 0 or 1, n (%) 36 (10.6) 13 (7.6) 24 (7.0) 15 (8.7) dlqi total score, mean (sd) 8.2 (5.8) 8.7 (5.9) 8.5 (5.9) 8.6 (5.9)   item 1, mean (sd) 1.8 (0.9) 1.9 (0.8) 1.8 (0.8) 1.9 (0.8) psd total score, mean (sd) 73.1 (41.2) 74.9 (43.0) 74.0 (38.4) 76.0 (41.2)   item 1, mean (sd) 5.6 (2.7) 5.9 (2.7) 5.8 (2.6) 6.0 (2.8)   item 2, mean (sd) 5.5 (2.9) 5.7 (3.0) 5.6 (2.8) 5.7 (3.0) intention-to-treat population. bmi, body mass index; dlqi, dermatology life quality index; pp-nrs, peak pruritus numeric rating scale; psd, psoriasis symptom diary; qd, once daily; sd, standard deviation. achieving an itch-free state as measured by pp-nrs score of 0 or 1 at weeks 2, 4, 8, and 12 ■ significance in achieving a pp-nrs score of 0 or 1 with tapinarof versus vehicle was demonstrated as early as week 2 (first visit) in psoaring 1 (p=0.0194) and week 4 in psoaring 2 (p=0.0004) ■ a significantly higher proportion of tapinarof-treated patients versus vehicle achieved a pp-nrs score of 0 or 1 at week 12: 49.6% vs 32.1% (p=0.0007) and 50.3% vs 27.3% (p<0.0001), respectively (figure 2) figure 2. rapid and significant achievement of an itch-free state (pp-nrs score of 0 or 1) with tapinarof cream 1% qd 0 0 2 4 8 12 10 20 30 40 60 50 p ro p o rt io n o f p a ti e n ts , % week p=0.0001 p=0.0007 49.6% 32.1% p=0.0026 tapinarof 1% qd (n=340) vehicle qd (n=170) p=0.0194 0 0 2 4 8 12 10 20 30 40 60 50 p ro p o rt io n o f p a ti e n ts , % week p<0.0001 p<0.0001 50.3% 27.3% p=0.0004 tapinarof 1% qd (n=343) vehicle qd (n=172) intention-to-treat, observed cases pp-nrs, peak pruritus numeric rating scale; qd, once daily. mean change in pp-nrs score from baseline at weeks 2, 4, 8, and 12 ■ itch assessed by pp-nrs was rapidly reduced with tapinarof versus vehicle, with significant improvements from week 2 (p=0.0162 and p<0.0001), the earliest measured time point, in psoaring 1 and 2, respectively ■ improvements from baseline reached –3.9 vs –2.9 (p=0.0002) and –3.0 vs –1.4 (p<0.0001) at week 12 (figure 3) figure 3. early, significant, and continued improvement in pp-nrs score from baseline –5 0 2 4 8 12 –4 –3 –2 0 –1 c h a n g e i n p p -n r s week –2.9 –3.9 tapinarof 1% qd (n=340) vehicle qd (n=170) p=0.0162 p=0.0003 p=0.0001 p=0.0002 –5 0 2 4 8 12 –4 –3 –2 0 –1 c h a n g e i n p p -n r s week –1.4 –3.0 tapinarof 1% qd (n=343) vehicle qd (n=172) p<0.0001 p<0.0001 p<0.0001 p<0.0001 intention-to-treat, observed cases. least squares mean (standard error). pp-nrs, peak pruritus numeric rating scale; qd, once daily. mean change in dlqi item 1 rating from baseline at weeks 4 and 12 ■ significant improvements in dlqi itch item 1 were achieved by week 4, the earliest measured time point, with tapinarof vs vehicle, with mean changes of –1.0 vs –0.7 (p=0.0026) and –0.9 vs –0.3 (p<0.0001) at week 12, for psoaring 1 and 2, respectively (figure 4) figure 4. significant improvement in dlqi itch item 1* rating from baseline at weeks 4 and 12 –1.2 –1.0 –0.8 –0.6 –0.4 –0.2 0 c h a n g e i n d l q i it e m 1 week 4 δ –0.24 p=0.0003 tapinarof cream 1% qd vehicle qd –0.5 –0.8 week 12 δ –0.25 p=0.0026 –0.7 –1.0 week 4 δ –0.40 p<0.0001 –0.4 –0.8 week 12 δ –0.52 p<0.0001 –0.3 –0.9 *dlqi item 1 evaluates itch, soreness, painfulness, or stinging. intention to treat, observed cases. least squares mean (standard error). dlqi, dermatology life quality index; qd, once daily. mean change in psd itch severity item rating from baseline at weeks 2, 4, 8, and 12 ■ itch severity was rapidly reduced with tapinarof versus vehicle with statistically significant improvements as early as week 4 in psoaring 1 (p=0.0003) and week 2 (p<0.0001) in psoaring 2 ■ severity decreased by –3.9 vs –2.9 and –3.1 vs –1.4 (both p<0.0001) from baseline at week 12 in psoaring 1 and 2, respectively (figure 5) figure 5. early and sustained improvement in psd itch severity item rating from baseline at weeks 2, 4, 8, and 12 0 tapinarof 1% qd (n=340) vehicle qd (n=170) –5 0 2 4 8 12 –4 –3 –2 0 –1 c h a n g e i n p s d i tc h s e v e ri ty i te m –2.9 –3.9p=0.0003 p=0.0003 p<0.0001 –5 2 4 8 12 –4 –3 –2 0 –1 c h a n g e i n p s d i tc h s e v e ri ty i te m –1.4 –3.1p<0.0001 p<0.0001 p<0.0001 p<0.0001 week week tapinarof 1% qd (n=343) vehicle qd (n=172) intention-to-treat, observed cases. least squares mean (standard error). psd, psoriasis symptom diary; qd, once daily. mean change in psd itch bother item rating from baseline at weeks 2, 4, 8, and 12 ■ patients reported significantly less bothersome itch symptoms with tapinarof versus vehicle by week 2 (p=0.0022 and p<0.0001) in psoaring 1 and 2, respectively ■ improvements with tapinarof were significant versus vehicle at all evaluations, reaching changes of –3.9 vs –2.9 and –3.0 vs –1.1 (both p<0.0001) from baseline at week 12 in psoaring 1 and 2, respectively (figure 6) figure 6. rapid and significant improvement in psd itch bother item rating from baseline at weeks 2, 4, 8, and 12 tapinarof 1% qd (n=340) vehicle qd (n=170) tapinarof 1% qd (n=343) vehicle qd (n=172) –5 –4 –3 –2 0 –1 c h a n g e i n p s d i tc h b o th e r it e m –2.9 –3.9 p=0.0022 p<0.0001 p=0.0009 p<0.0001 –5 –4 –3 –2 0 –1 c h a n g e i n p s d i tc h b o th e r it e m –1.1 –3.0p<0.0001 p<0.0001 p<0.0001 p<0.0001 0 2 4 8 12 2 4 8 12 week week intention-to-treat, observed cases. least squares mean (standard error). psd, psoriasis symptom diary; qd, once daily. safety ■ treatment-emergent adverse events (teaes) were mostly mild to moderate and discontinuations due to teaes were low conclusions ■ tapinarof cream 1% qd demonstrated rapid, clinically meaningful, and statistically significant improvements in itch across multiple outcome measures, from the earliest visit at week 2 through week 12, in the phase 3 pivotal trials ■ significantly more tapinarof-treated patients achieved an itch-free state of pp-nrs=0 or 1 compared with vehicle-treated patients ■ tapinarof cream 1% qd is a well-tolerated treatment option for patients with mild to severe plaque psoriasis, including when applied to sensitive and intertriginous skin areas11 ■ achieving an itch-free state is an essential target for decreasing the burden of disease and improving hr-qol for patients with plaque psoriasis references 1. amatya b, et al. j eur acad dermatol venereol. 2008;22:822–826. 2. szepietowski jc, reich a. eur j pain. 2016;20:41–46. 3. yosipovitch g, et al. br j dermatol. 2000;143:969–973. 4. komiya e, et al. int j mol sci. 2020;21:8406. 5. lebwohl mg, et al. am j clin dermatol. 2016;17:87–97. 6. dermavant sciences. vtama (tapinarof) cream, 1%: us prescribing information. 2022. https://www.vtama. com/docs/dmvt_vtama_pi.pdf. accessed october 2022. 7. lebwohl mg, et al. n engl j med. 2021;385:2219–2229. 8. yosipovitch g, et al. br j dermatol. 2019;181:761–769. 9. finlay ay, khan gk. clin exp dermatol. 1994;19:210–216. 10. lebwohl m, et al. int j dermatol. 2014;53:714–722. 11. strober b, et al. j am acad dermatol. 2022;87:800–806. acknowledgments trials funded by dermavant sciences, inc. the authors thank the investigators, patients and their families, and colleagues involved in the conduct of the trials. l.k. has served as a consultant/speaker/investigator/advisory board member for abbott laboratories, abbvie, ablynx, aclaris, acambis, allergan, inc., almirall, amgen, inc., anacor pharmaceuticals, anaptys, arcutis, arena, assos pharma, astellas pharma us, inc., asubio, bausch health, berlex laboratories (bayer healthcare pharmaceuticals), biogen idec, biolife, biopelle, bms, boehringer ingelheim, breckinridge pharma, cassiopea, centocor, inc., cellceutix, cipher, coherus, colbar, combinatrix, connetics corporation, coria, dermavant sciences, inc., dermira, dermik laboratories, dow pharmaceutical sciences, inc., dr. reddy’s lab, dusa, embil pharmaceuticals, eli lilly, eos, exeltis, ferndale laboratories, inc., foamix, ferrer, galderma, genentech, inc., glaxosmithkline, glenmark, health point, ltd, idera, incyte, intendis, innocutis, innovail, isdin, johnson & johnson, kyowa kirin, laboratory skin care inc., leo pharma, l’oreal, 3m, maruho, medical international technologies, merck, medicis pharmaceutical corp., merz, nano bio, novartis ag, nven pharmaceuticals, nucryst pharmaceuticals corp., obagi, onset, orthoneutrogena, pediapharma, pfizer, promius, puracap, pharmaderm, qlt, inc., quinnova, quatrix, regeneron, sanofi, serono (merck serono international sa), skinmedica, inc., stiefel laboratories, inc., sun pharma, taro, tolerrx, triax, ucb pharma, valeant pharmaceuticals intl., warner-chilcott, xenoport, and zage. m.z. has served as an advisor/consultant/investigator/owner/speaker for abbvie, all free clear, amgen, inc., anaptys bio, arcutis, asepticmd, biocon, cara, concert, dermavant sciences, inc., edessa biotech, eli lilly, epi health, evelo biosciences, fitbit, galderma, genentech, inc., incyte, l’oreal, leo pharma, level-ex, luum, novartis, oculus, peloton, pfizer, regeneron, sanofi, sun, trevi, ucb pharma, and vial. s.g.k. has served as an investigator/advisory board member/consultant for abbvie, aslan pharmaceuticals, arcutis biotherapeutics, castle biosciences, celldex therapeutics, galderma, genzada pharmaceuticals, incyte, johnson & johnson, leo pharma, novartis pharmaceuticals corporation, pfizer, regeneron pharmaceuticals, and sanofi. g.m.l. has served as a consultant/ speaker/investigator/advisory board member for and/or has received grants from abbvie, amgen, inc., bristol myers squibb, dermavant sciences, inc., dermtech, eli lilly, galderma, leo phama, janssen, novan, inc., pfizer, orthodermatologics, and ucb biopharma. h.g. has served as a consultant/speaker/investigator/advisory board member of abbvie, almirall, bristol myers squibb, cassiopea, dermavant sciences, inc., eli lilly, galderma, incyte, isdin, leo pharma, pfizer, and sun pharma. t.c. has served as an advisor and speaker for dermavant sciences, inc. p.m.b., d.s.r., and a.m.t. are employees of dermavant sciences, inc., with stock options. editorial and medical writing support under the guidance of the authors was provided by apothecom, uk, and was funded by dermavant sciences, inc., in accordance with good publication practice (gpp) guidelines (ann intern med. 2022;175:1298–1304). contact dr leon kircik at wedoderm@yahoo.com. rapid improvements in itch with tapinarof cream 1% once daily in two phase 3 trials in adults with mild to severe plaque psoriasis leon kircik,1 matthew zirwas,2 shawn g. kwatra,3 g. michael lewitt,4 holly glover,5 tomas chao,6 philip m. brown,7 david s. rubenstein,7 anna m. tallman7 1icahn school of medicine at mount sinai, new york, ny, usa; 2bexley dermatology, bexley, oh, usa; 3johns hopkins university school of medicine, baltimore, md, usa; 4illinois dermatology institute, chicago, il, usa; 5dermatology and skin cancer surgery center, waxahachie, tx, usa; 6atlanta north dermatology, woodstock, ga, usa; 7dermavant sciences, inc., morrisville, nc, usa fall clinical poster 9.27.19 brandon kirsch, md1, janet dubois, md2, deepak chadha, ms, mba, rac1 1brickell biotech, inc., boulder, co, 2dermresearch inc., austin, tx a multi-center, open-label study to assess pharmacokinetics (pk), safety and tolerability of sofpironium bromide gel, 15% applied topically to children and adolescents, ≥9 to <17 years of age, with axillary hyperhidrosis excessive sweating affects approximately 15 million americans. sofpironium bromide is a retro-metabolically designed analog of glycopyrrolate (anticholinergic) in development for the topical treatment of axillary hyperhidrosis. retro-metabolically designed drugs are rapidly metabolized in the bloodstream, allowing for potentially optimal therapeutic effect at application sites with minimal systemic side effects . primary hyperhidrosis has a prevalence rate of 2.1% for individuals <18 years of age with any area of involvement, with approximately 65% (1.4%) experiencing axillary hyperhidrosis.1 the safety, tolerability and efficacy of topical treatments for axillary hyperhidrosis have rarely been studied in the pediatric population. twenty-five subjects ranging in age from 9 to 16 years with axillary hyperhidrosis of at least 6 months duration were enrolled. the objectives of the study were to assess systemic exposure, safety and effectiveness of sofpironium bromide gel, 15% following application to both axillae for 7 (± 1) days. based on a previously observed half-life of 5 to 6 hours in adult subjects, steady-state was anticipated within 24 hours; thus, a 1-week treatment duration was deemed sufficient to evaluate systemic absorption after repeat administration. table 1. demographics and baseline characteristics following topical application of sofpironium gel, sofpironium and its primary metabolite (bbi-4010) were detected in 11 subjects and 6 subjects, respectively. systemic exposure to sofpironium and bbi-4010 was typically minimal following the first dose (day 1) and after multiple doses (day 8; 24 hours after the last dose). there was no evidence of accumulation. four treatment emergent adverse events (teaes) were observed, including one of influenza. the remaining three (dry eyes, blurred vision, and urinary hesitation) were expected systemic anticholinergic symptoms. no subject was withdrawn from the study due to an adverse event (ae), and no concomitant medication was necessary. for the validated patient-reported outcome measures hyperhidrosis disease severity measure-axillary (hdsm-ax; >12 years of age) and hdsm-ax-child (>9 to <12 years of age), changes from baseline to day 8 in mean scores ranged from -3.4 to 0.3 with a mean of -1.23 and a median change of -1.00. a change of -1.00 has been defined to represent clinically meaningful improvement. similar improvements in the severity of underarm sweating were reported based on the patient global impression of severity (pgi-s) scale at day 8. figure 1: sofpironium and bbi-4010 plasma concentrations (day 1 to day 7)4,5,6 all data presented are for the study safety population 1a treatment emergent ae (teae) is defined as any ae occurring on or after first dose. 2subjects are counted only once at the strongest relationship to the study medication. figure 2: hdsm-ax and pgi-s responses from baseline to day 8 (eot)8,9 sofpironium bromide, an investigational agent, has the potential to address an unmet need for a noninvasive, topical primary axillary hyperhidrosis treatment, which is safe and effective for use in the pediatric population. pharmacokinetic findings were consistent with previous investigational evaluations in adults where systemic sofpironium and bbi-4010 concentrations were also variable, sporadic, and minimal. as anticipated with retro-metabolic drug design, sofpironium bromide exhibited low numbers of systemic anticholinergic aes, and all were mild or moderate in severity and transient, with no treatments discontinuations. clinically meaningful improvements in the frequency and severity of underarm sweating were reported as early as day 8. this clinical study and preparation of the abstract were supported by brickell biotech, inc. funding statement variable sb gel, 15% (n=25) age (years) mean (sd) 13.4 (2.14) min, max 9, 16 gender male 12 (48.0%) female 13 (52.0%) hdsm-ax mean (sd) 2.76 (0.557) min, max 1.7, 3.7 pgi-s none 0 (0.0%) mild 0 (0.0%) moderate 9 (36.0%) severe 12 (48.0%) very severe 4 (16.0%) 0 1 2 3 4 day 1 day 8 h d s m -a x s co re study day hdsm-ax scores 0% 10% 20% 30% 40% 50% 60% none mild moderate severe very severe p e rc e n t r e sp o n se s severity pgi-s responses day 1 day 8 sb gel, 15% (n=25) subjects with teaes 3 (12.0%) number of teaes 4 dry eye 1 (4.0%, mild) vision blurred 1 (4.0%, moderate) influenza 1 (4.0%, moderate) urinary hesitation 1 (4.0%, mild) subjects with saes 0 (0.0%) discontinuations due to teaes 0 (0.0%) burning itching stinging scaling erythema minimal 1 (4.0%) 3 (12.0%) 2 (8.0%) 0 (0.0%) 3 (12.0%) mild 1 (4.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 2 (8.0%) moderate 1 (4.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) severe 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) table 3: summary of local tolerability at day 83 table 2: summary of teaes1,2 3maximum severity assessed for either axilla is reported. conclusion screening/ day -35 to day -3/visit 1 • first application in clinic • pk sample collection pre-dose (t0), 1 and 4 hrs (±5 min), and 8 hrs (± 15 min)1, post-dose baseline day 1/visit 2 end of study2 day 21 (± 3 days)/visit 5 optional enrollment in extension study (bbi-4000-cl-108) end of treatment/early termination day 8 (±1 day)/visit 4 1 may be done as a home visit 2 only complete if subject does not continue in the optional extension study (bbi-4000-cl-108) day 2/visit 31 • pk sample 24 hrs (±1 hr) after last dose • pk sample 24 hours (±1 hr) after first dose • second application in clinic/home day 3 day 4 day 5 day 6 day 7 (±1 day) self-application at home qd results introduction methods academic poster presented at the 2019 fall clinical dermatology conference | las vegas, nv | october 17 20, 2019 4pk population includes all 25 subjects. 5a total of 14 subjects had no quantifiable sofpironium through the pk time-course. 6a total of 19 subjects had no quantifiable bbi-4010 through the pk time-course. 7limit of quantification (loq) of 0.050 ng/ml for sofpironium and bbi-4010 8the hyperhidrosis disease severity measure-axillary© (hdsm-ax) is an 11-item measure of axillary hyperhidrosis severity. a change of -1.00 has been defined to represent clinically meaningful improvement. 9the patient global impression of severity (pgi-s) scale is a global index that may be used to rate the severity of a specific condition. 1doolittle j, walker p, mills t, thurston j. hyperhidrosis; an update on prevalence and severity in the united states. arch dermatol res. 2016; 308:743-749. references 0 2 4 6 8 10 12 14 16 d ay 1 , 0 h d ay 1 , 1 h d ay 1 , 4 h d ay 1 , 8 h d ay 1 , 2 4h d ay 8 , 2 4h s o fp ir o n iu m s am p le c o n ce n tr at io n (n g /m l) collection day, nominal hour sofpironium concentrations 0 2 4 6 8 10 12 14 16 d ay 1 , 0 h d ay 1 , 1 h d ay 1 , 4 h d ay 1 , 8 h d ay 1 , 2 4h d ay 8 , 2 4h b b i4 0 1 0 c o n ce n tr at io n (n g /m l) collection day, nominal hour bbi-4010 concentrations powerpoint presentation background • patients with cutaneous melanoma (cm) have an individual recurrence risk determined by clinical, pathological, and genetic features. • the 31-gene expression profile (31-gep) test is an independent significant predictor of 5-year risk of recurrence and distant metastasis.1-7 • 31-gep results classify tumor biology as lowest-risk (class 1a), low-risk (class 1b), high-risk (class 2a), and highest-risk (class 2b): development and validation of a nomogram incorporating the 31-gep test and clinicopathologic factors for accurate prediction of recurrence risk in patients with cutaneous melanoma thorpe, r.1; caruso, h.g.2; covington, k.r.2; brodland, d.3; zitelli, j.3 1. ada west dermatology, 2. castle biosciences, inc., 3. zitelli and brodland, p.c. all patients n=685 class 1a n=557 class 1b n=41 class 2a n=33 class 2b n=54 age median (range), years 67 (22-90) 65 (22-90) 71 (33-90) 71 (52-91) 74 (26-90) breslow thickness (range), mm 0.5 (0.1-13) 0.5 (0.1-5) 0.8 (0.2-6) 1.2 (0.2-7.5) 2.6 (0.2-13) male 60% (411/685) 59% (330/557) 51% (21/41) 79% (26/33) 63% (34/54) ulceration present 7% (50/685) 3% (17/557) 7% (3/41) 6% (2/33) 52% (28/54) mitotic rate ≥ 2 mm2 18% (121/685) 9% (52/557) 32% (13/41) 52% (17/33) 72% (39/54) objective: to develop a nomogram tool combining 31-gep class and clinicopathologic risk features for predicting cm recurrence. 1. gerami et al. clin cancer res. 2015 jan 1;21(1):175-83. 2. gerami et al. jaad. 2015 may;72(5):780-5.e3. 3. zager et al. bmc cancer. 2018 feb 5;18(1):130. 4. gastman et al. jaad. 2019 jan;80(1):149-157.e4. 5. hsueh et al. j hematol oncol. 2017 aug 29;10(1):152. 6. greenhaw et al. dermatol surg. 2018 dec;44(12):1494-1500. 7. keller et al. cancer med. 2019 may;8(5):2205-2212. references disclosures castle biosciences, inc (cbi) provided statistical analysis support for nomogram development. krc and hgc are employees and option holders of cbi. prospective cohort registry is independently managed by the cutaneous oncology research consortium (corc). rt, db, jz have no relevant disclosures. methods: nomogram development table 1. patient clinical and pathologic features per 31-gep class results • a prospective cohort of 685 patients from 9 dermatology centers with minimum 1yr follow-up or a recurrence event at any time was included in nomogram development. • a logistic regression model was fitted on clinical and pathological data to determine relative predictive value for recurrence risk. covariate inclusion for the model was selected by lowest bayesian information criteria (bic) value with fewest clinical features. • the nomogram was validated on a retrospective cohort of 901 stage i-iii cm patients with > 5 years follow-up or a recurrence event, and goodness of fit was determined by linear regression. gep class n events 1.5-yr rfs class 1a 557 14 (2.5%) 98.9% (98.0-99.8%) class 1b 41 6 (14.6%) 97.6% (93.0-100%) class 2a 33 4 (12.1%) 93.9% (86.1-100%) class 2b 54 24 (44.4%) 70.3% (59.1-83.6%) p<0.0001 class 1a class 1b class 2a class 2b r f s time (years) figure 1. multivariate cox regression analysis of 31-gep and clinicopathologic features figure 2. kaplan-meier estimation of recurrence-free survival (rfs) • this nomogram combines the 31-gep test result with clinical features to create a clinically useful, accurate tool for determining an individual’s risk of recurrence to optimize patient care. • because sentinel lymph node (sln) status is not a feature in this nomogram, this tool can be used to provide patient risk of recurrence prior to or in the absence of a sln biopsy. • a future aim of this study is to generate a mobile application for conversion of clinical and molecular data to a patient’s recurrence risk. conclusions figure 3: optimum model selected by bic figure 4. validation of the nomogram in a retrospective cohort of 901 patients with stage i-iii cutaneous melanoma s e rv e d e c u rr e n c e a te redicted ecurrence ate 2 2 predicted recurrence rate o b s e rv e d r e c u rr e n c e r a te p < 0.0001 patients with stage i-iii melanoma class 1: low risk of sln positivity (eligible t1-t2) low risk of melanoma recurrence (t1-t4) class 2: higher risk of sln positivity (eligible t1-t2) high risk of melanoma recurrence (t1-t4) •quantifies expression of 31 genes from primary tumor using rt-pcr •applies a validated algorithm •accurately classifies patients as low or high risk 1a lowest risk 2b highest risk 2a increased risk 1b low risk figure 5. impact of t stage and 31-gep on risk of recurrence ajcc v8 gep class 1a gep class 1b/2a gep class 2b t1a 1.9% 2% 5% 9% t1b 6.9% 4% 9% 19% t2a 12.1% 7% 19% 24% t2b 25.0% 15% 29% 45% t3a 25.0% 11% 27% 40% t3b 45.0% 19% 35% 53% t4a 37.5% 15% 29% 45% t4b 85.7% 48% 71% 83% results continued rfs hazard ratio skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 595 brief articles painful retiform purpura with cutaneous necrosis alfredo siller jr., md1, joseph jebain md1, yomna amer ba2, christopher t. haley md3, leon chen md4, stephen k. tyring md, phd4 1center for clinical studies, webster, tx 2university of louisville school of medicine, ky 3department of dermatology, baylor scott & white medical center, temple, tx 4department of dermatology, university of texas health science center at houston, houston, tx levamisole is an antihelminthic veterinary medication that was previously used as an immunomodulator in humans to treat malignancies, autoimmune disorders, and pediatric nephrotic syndrome.1 the drug was removed from american and canadian markets in 2000 and 2003, respectively, due to adverse effects of agranulocytosis, leukopenia, thrombocytopenia, and skin vasculitis.1-3 since 2003, levamisole has been detected as a cocaine contaminant.2 levamisole is an attractive diluent of cocaine because it passes the “bleach test,” a street test for cocaine purity.3 additionally, levamisole may amplify the euphoric high of cocaine through inhibition of monoamine oxidase and catechol-omethyltransferase,1,3 and potentiation of nicotinic acetylcholinergic signals.2 in 2009, 71% of the cocaine samples in the united states,4 and 50% of samples in the united kingdom tested positive for levamisole.5 the concentration of levamisole in cocaine has also been increasing,2 causing cases of levamisole-induced toxicity to be more common. we herein report a case of a 46-year-old caucasian male who developed levamisole-induced vasculitis from crack cocaine use. a 46-year-old caucasian male with a past medical history significant for hepatitis c abstract levamisole-induced vasculitis is characterized by a painful, purpuric rash in a retiform or stellate pattern with or without central necrosis that commonly involves the trunk, extremities, digits, distal nose, cheeks, and ear helices. this clinical syndrome is associated with the use of levamisoleadultered cocaine. histologic findings for levamisole-induced vasculitis are not disease specific but may include leukocytoclastic vasculitis, microvascular thrombosis, and panniculitis. laboratory findings of levamisole-induced toxicity include agranulocytosis, neutropenia, hepatotoxicity, glomerulonephritis, pulmonary hemorrhage, and positive p-anca, c-anca tests, ana, or lupus anticoagulant. the differential diagnosis for levamisole-induced vasculitis includes leukocytoclastic vasculitis, drug reaction, cryoglobulinemia, idiopathic thrombocytopenic purpura, granulomatosis with polyangiitis, churg-strauss syndrome, and polyarteritis nodosa. levamisole-induced vasculitis typically resolves spontaneously with cessation of cocaine use however; recurrence is common following re-exposure. introduction case presentation skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 596 virus (hcv) infection, metastatic melanoma, and years of crack cocaine use presented to the emergency department with a one-week history of painful lesions involving the nose, limbs, and mouth. skin exam showed painful purpura of the ears and right nasal ala (figure 1a), retiform purpura with necrosis of all four extremities (figure 1b), and an ulcer of the left buccal mucosa (figure 1c). he denied any personal history or family history of vasculitis, but reported an increase in crack cocaine use shortly before the onset of his skin lesions and a similar episode following cocaine use 5 years ago. his initial laboratory values were significant for microcytic anemia, decreased complement levels, and a positive drug screen for cocaine. hcv viral load was undetectable and serum cryoglobulins were negative. autoimmune workup was positive for anti-myeloperoxidase anti-neutrophil cytoplasmic antibodies (p-anca) and antipr3 anti-neutrophil cytoplasmic antibodies (c-anca), and negative for anti-nuclear antibodies, anti-double-stranded dna antibodies, and anti-smith antibodies. given the temporal relationship of cocaine use to the onset of the purpura, characteristic ear involvement, and positive p-anca and c-anca tests, the patient was diagnosed with levamisole-induced vasculitis. he agreed to cease cocaine use and was treated with high-dose corticosteroids and debridement of necrotic tissue. he later developed secondary methicillin resistant staphylococcus aureus infection of his right lower extremity, which was successfully treated with trimethoprimsulfamethoxazole and amoxicillin clavulanate. characteristic findings of levamisole-induced toxicity include purpura, agranulocytosis, neutropenia, and hepatotoxicity, along with infrequent findings of glomerulonephritis and pulmonary hemorrhage. approximately 90% of patients have cutaneous manifestations, most frequently purpura of the ear helices and cheeks and retiform purpura of the extremities. the purpura often become necrotic and may develop bullae and abscesses.1,4 fever, oral sores, fatigue, and dyspnea are also common manifestations.6 the differential diagnosis for levamisoleinduced vasculitis includes leukocytoclastic vasculitis, drug reaction, cryoglobulinemia, idiopathic thrombocytopenic purpura, granulomatosis with polyangiitis, churgstrauss syndrome, and polyarteritis nodosa.2,6 histologic findings for levamisoleinduced vasculitis are not disease specific but may include leukocytoclastic vasculitis, thrombosis, and panniculitis.2,6 diagnosis is therefore made through laboratory values and clinical history. useful tests include complete blood cell count with differential, comprehensive metabolic panel, coagulation studies, antineutrophil cytoplasmic antibodies, antiphospholipid antibodies, cryoglobulins, and lupus anticoagulants. 2,6 the majority of patients with levamisoleinduced vasculitis are positive for p-anca, while c-anca positivity has been reported in about 50% of patients.3,4,7 anti–doublestranded dna and lupus anticoagulant studies may also be positive.2 the antihuman elastase antibody is a sensitive and specific test to cocaine-induce lesions8 which can be helpful to distinguish levamisole-induced vasculitis from ancaassociated vasculitis.2 in a study examining available case reports, anti-human elastase antibody was the only antibody found to be positive in all patients with levamisolediscussion skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 597 figure 1 levamisole-induced vasculitis in a 46-year-old male. (a) purpura of right ear. (b) purpura with necrosis of left lower extremity. (c) ulcer of left buccal mucosa. induced vasculitis, and this antibody positivity was more indicative of levamisoleinduced vasculitis than other autoimmune vasculitis.9 testing urine for levamisole is not recommended as it has a short half-life of 5.6 hours, and only 2% to 5% of the parent drug is present within 48 hours of use. additionally, levamisole testing is expensive and limited in availability.3,6 the propensity for levamisole-induced vasculitis to affect the ears and zygomatic area also helps distinguish it from other ancaassociated vasculitides.1 levamisole-induced vasculitis typically resolves spontaneously with cessation of cocaine use. adjuvant care can include systemic corticosteroids, surgical debridement, antibiotics, and plasmapheresis.6,10 it is important to note, however, that levamisole-induced vasculitis frequently recurs following re-exposure to contaminated cocaine and therefore, complete abstinence must be counseled. 11 the use of levamisole as a cocaine diluent has become increasingly popular, making awareness of levamisole-induced vasculitis imperative for clinicians. to distinguish levamisole-induced vasculitis from other forms of vasculitis, anti-human elastase antibody has been shown to be a useful tool, as it is negative in other types of autoimmune vasculitis. conflict of interest disclosures: none funding: none corresponding author: alfredo siller jr., md 451 north texas avenue webster, tx 77598 phone: 254-624-3016 email: asillermd@gmail.com references: 1. nolan a, jen k. pathologic manifestations of levamisole-adulterated cocaine exposure. diagn pathol. 2015;10:48. conclusion skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 598 2. lee k, ladizinski b, federman d. complications associated with use of levamisole-contaminated cocaine: an emerging public health challenge. mayo clin proc. 2012;87(6):581-586. 3. abdul-karim r, ryan c, rangel c, emmett m. levamisole-induced vasculitis. proc (bayl univ med cent). 2013;26(2):163-165. 4. jin q, kant s, alhariri j, geetha d. levamisole adulterated cocaine associated anca vasculitis: review of literature and update on pathogenesis. j community hosp intern med perspect. 2018;8(6):339-344. 5. cocaine adulterated with levamisole on the rise. erowid;2009 available at: https://www.erowid.org/chemicals/cocaine/cocain e_article2.shtml. (accessed 15 mar 2019). 6. chung c, tumeh pc, birnbaum r, et al. characteristic purpura of the ears, vasculitis, and neutropenia--a potential public health epidemic associated with levamisole-adulterated cocaine. j am acad dermatol. 2011;65(4):722-725.e722. 7. mcgrath m, isakova t, rennke h, mottola a, laliberte k, niles j. contaminated cocaine and antineutrophil cytoplasmic antibody-associated disease. clin j am soc nephrol. 2011;6(12):2799-2805. 8. wiesner o, russell ka, lee as, jenne de, trimarchi m, gregorini g, specks u. antineutrophil cytoplasmic antibodies reacting with human neutrophil elastase as a diagnostic marker for cocaine-induced midline destructive lesions but not autoimmune vasculitis. arthritis rheum. 2004 sep;50(9):2954-65. 9. pearson t, bremmer m, cohen j, driscoll m. vasculopathy related to cocaine adulterated with levamisole: a review of the literature. dermatol online j. 2012 jul 15;18(7):1. 10. hahn e, bogoch ii. levamisole-induced vasculitis in a cocaine user. j rheumatol. 2015;42(10):1924-1925. 11. van der veer t, pennings e, tervaert j, korswagen l. levamisole-contaminated cocaine: a hairy affair. bmj case rep. 2015;2015. skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 182 short communications pediatric inflammatory epidermolysis bullosa acquisita in a patient with oculocutaneous albinism timothy j. orlowski md1, michel m. hatch md2, rebecca kissel md2, peter pavlidakey md2, lauren v. graham md phd2 1479th flying training group, aviation medicine department, naval hospital pensacola, pensacola, fl 2university of alabama at birmingham, department of dermatology, birmingham, al a 15-year-old caucasian male with a history of oculocutaneous albinism (oca) was referred to our dermatology clinic for a 4year history of erythematous plaques and clear-yellow vesicles and bullae on his face, neck, upper chest, and extremities. the vesicles previously erupted once to twice a year, but recently have occurred more frequently and become less responsive to oral and topical steroids. during an acute episode, he would develop either a single or numerous, pruritic blisters on his face, trunk and upper extremities. the patient and his mother were unable to identify any triggers and due to the patient’s history of oca, he practiced strict photoprotection. review of systems was negative and he denied any ocular or mucosal lesions. the patient’s medications were mometasone furoate/formoterol fumarate dihydrate, cetirizine, and montelukast. physical exam was remarkable for scattered erythematous scaly papules and polycyclic plaques on the chest, upper extremities, face and hands, as well as a few intact clear-yellow vesicles. punch biopsies of the left chest and right arm were performed and histopathology revealed subepidermal bullae formation with neutrophils and a few eosinophils (figure 1a). direct immunofluorescence (dif) of the left chest punch biopsy was positive for linear and granular deposition of igg, iga, igm, c3 and fibrin along the dermalepidermal junction (figure 1b). serologic testing for complement fixing antinuclear antibodies (cana), ana, ro (ss-a) and la (ss-b), anti-smith, anti-dsdna, anti-rnp, anti-cardiolipin were negative; however, type vii collagen antibodies were detected by elisa at 7.6 u/ml. complete blood count, cmp, esr, crp and complement levels were all within normal limits. a preliminary diagnosis of inflammatory epidermolysis bullosa acquisita (eba) was made and the patient was started on dapsone 50 mg daily and prednisone 30 mg in conjunction with rheumatology. the patient’s blisters resolved almost completely within several days with no residual scarring or milia formation. epidermolysis bullosa acquisita (eba) is rarely seen in the pediatric population and can have various clinical presentations. in addition to clinical manifestations of the disease, serologic, histologic and immunofluorescence findings are used to make the diagnosis. this case describes an unusual instance of pediatric inflammatory epidermolysis bullosa in a patient with skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 183 oculocutaneous albinism and multiple positive dif reactants. while deposits of igg, iga, igm and c3 along the basement membrane zone (bmz) have been reported previously, to our knowledge this is the first case of pediatric inflammatory eba to demonstrate positivity of all the above reactants.1,2 this pattern is more commonly found in cutaneous lupus, and while a diagnosis of bullous lupus was considered, this patient had no evidence of systemic lupus. however, this finding does suggest potential overlap in pediatric inflammatory eba and bullous lupus. uv radiation can cause damage to the bmz and increase the transcriptional expression of type vii collagen antibodies in dermal fibroblasts.4,5 we hypothesize that due to his history of oca, our patient’s increased sensitivity to solar radiation led to the exposure of bmz antigens and development of type vii collagen autoantibodies. ultimately, this resulted in the clinical manifestation of inflammatory eba. figure 1. (a) mid-chest with erythematous macules and bullae. figure 1. (b) h&e, 10x magnification biopsy specimen demonstrating subepidermal bullae formation with neutrophils and eosinophils. conflict of interest disclosures: dr. orlowski was active duty air force at the time of submission. the views expressed are those of the authors and are not to be construed as official or as representing those of the us air force or the department of defense. dr. orlowski was a full time federal employee at the time portions of this work were completed. they are in the public domain. dr. hatch, dr. kissel, and dr. pavlidakey have no conflicts of interest to declare. dr. graham has received clinical research support from pfizer and octapharma. dr. graham is a consultant for ucb and has received an honorarium from the national psoriasis foundation. funding: none corresponding author: lauren v. graham 1720 university blvd, suite 500 department of dermatology birmingham, al 35294, usa phone: 205-934-5188 email: lvgraham@uabmc.edu mailto:lvgraham@uabmc.edu skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 184 references: 1. mayuzumi m, akiyama m, nishie w, ukae s, abe m, sawamura d, hashimoto t, shimizu h. childhood epidermolysis bullosa acquisita with autoantibodies against the noncollagenous 1 and 2 domains of type vii collagen: case report and review of the literature. br j dermatol. 2006 nov;155(5):1048-1052. 2. trigo-guzmán fx, conti a, aoki v, maruta cw, santi cg, resende silva cm, gontijo b, woodley dt, rivitti ea. epidermolysis bullosa acquisita in childhood. j dermatol. 2003 mar;30(3):226-229. 3. intong lr, murrell df. management of epidermolysis bullosa acquisita. dermatol clin. 2011 oct;29(4):643-647. 4. amano s. possible involvement of basement membrane damage in skin photoaging. j investig dermatol symp proc. 2009 aug;14(1):2-7. 5. nakano h, gasparro fp, uitto j. uva-340 as energy source, mimicking natural sunlight, activates the transcription factor ap-1 in cultured fibroblasts: evidence for involvement of protein kinase-c. photochem photobiol. 2001 aug;74(2):274-282. skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 46 brief articles successful treatment of multiple post-operative keratoacanthomas with topical 5-fluorouracil nelson c. ugwu, bs1, nour kibbi, md2 1department of dermatology, yale university school of medicine, new haven, ct 2stanford dermatologic surgery, redwood city, ca keratoacanthoma (ka) is a rapidly growing, low-grade variant of cutaneous squamous cell carcinoma that often arises as a solitary lesion on sun-exposed skin in adults over age 40. following a rapid growth phase, kas may spontaneously regress, but predicting which tumors will do so is challenging. for this reason, kas are often treated with surgery, however, non-surgical modalities have also been employed, including intralesional 5-fu, intralesional methotrexate, or oral retinoids. response rates with these non-surgical therapies vary, ranging from 83 to 100%.1 most kas arise sporadically, but kas have also been reported as a reactive phenomenon following traumatic procedures, such as skin surgery,2 skin grafting,3 laser resurfacing,4 and spontaneous injuries such as piercing or scratch injuries.5 here, we present the case of a very elderly gentleman with multiple post-operative eruptive kas treated successfully with topical 5-fluorouracil and review the literature on kas treated with topical 5-fluorouracil. a 94-year-old healthy man presented with a 3-4 week history of five rapidly enlarging, crateriform nodules with central hemorrhagic crust on the right lower leg (figure 1a). some of the lesions were painful to the touch. approximately 6 weeks prior, the patient had undergone mohs micrographic surgery (mms) for a welldifferentiated squamous cell carcinoma of the lower extremity that was repaired with a linear closure. the patient had a history of multiple non-melanoma skin cancers treated with mms. he declined further surgical intervention on the new lesions, including abstract keratoacanthomas (kas) are fast-growing tumors and can be difficult to distinguish from squamous cell carcinomas (sccs). most kas are sporadic, but kas may also arise following traumatic procedures. we report the case of a 94-year-old male who developed multiple kas following surgical excision of an scc on the right lower extremity. the patient declined additional procedures including biopsy, surgery, or intralesional therapy. he was started on 5% topical fu using a 2 week on, 2 week off regimen for 16 weeks with resolution of disease. no recurrence was noted at 13 months. topical 5-fu is a conservative, non-invasive treatment for post-traumatic kas that is particularly suitable in the elderly, in whom the risks and morbidity from surgical or other non-invasive approaches are worth considering. introduction case presentation skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 47 figure 1. (a) on the right lower leg were five crateriform friable nodules which developed following excision of a welldifferentiated squamous cell carcinoma. (b) following two months of cyclical topical 5% 5-fluorouracil therapy, there was a notable reduction in nodule size, crusting of the lesions, and a moderate irritant reaction of the lower extremity. (c) the lesions resolved after four months of cyclical therapy. biopsy and did not wish to undergo any systemic therapy. he had previously tried tazarotene 0.1% cream without improvement. he elected to initiate 5fluorouracil 5% cream twice daily on an alternating 2 weeks on then 2 weeks off regimen without occlusion. two months following initiation of therapy, he was noted to have a significant response with reduction in nodule size and a moderate irritant reaction of the lower extremity (figure 1b). he declined topical corticosteroids for the irritant reaction and used emollients as needed between the 5-fluorouracil treatments. four months after presentation, the lesions had resolved (figure 1c), and the patient was using 5-fluorouracil as needed. the patient was seen in close clinical follow-up until 13 months following initial presentation and was noted to have no recurrence. he had continued to use topical 5-fluorouracil for other keratotic lesions on his upper and lower extremities that failed to regress spontaneously. he died two months later of unrelated causes. this case report highlights the phenomenon of multiple post-operative kas arising in an elderly man. while biopsy and/or additional discussion a. b. c. skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 48 table 1. summary of 43 keratoacanthoma cases treated with topical 5-fluorouracil (5-fu) therapy. authors number of patients mean age (range) sex tumor location number of tumors sporadic/tri ggering event treatment regimen adjuvant treatment patients achieving cr overall follow-up additional treatments for patients with incomplete responses grupper 19708 15 59.9 (38-80) 9m, 6f head (13) and upper extremity (2) solitary lesions 9 sporadic, 6 after initial total excision 5% 5fu ointment 1-2 times daily for 1-2 weeks then 2% 5-fu ointment or 2% 5-fu gel under occlusion for 1-4 weeks none 12/15 at 35 weeks 2-18 months. no recurrence 2/3 patients underwent surgery at 3 weeks (1 pr, 1 no response to 5-fu). 1/3 continued 5topical fu goette et al 19829 14 66 (44-80) 6m, 8f head (2), neck (2), upper extremity (5), lower extremity (3), chest (1), shoulder (1) solitary lesions sporadic 20% 5fu ointment, 2-3 times daily for 2-4 weeks, (-) or (+) occlusion none 14/14 at 17 weeks 1-7 weeks none gray et al 199912 2 74 (68-80) 2m head (2), neck (2), forearm and hand (5), lower leg (3), chest (1), shoulder (1) solitary lesions sporadic 5% 5fu cream daily without occlusion for 4-8 weeks none 1/2 at 8 weeks 8 weeks 1 patient underwent biopsy with electrodessicatio n at 4 weeks after pr thompson et al 201411 10 74.4 (52-92) 9f, 1m lower extremity (5) and head (5) solitary lesions sporadic short-contact (1 hr) topical 5% 5-fluorouracil cream twice daily until resolution none 9/10 at 4-6 weeks 4-6 weeks 1 patient underwent mohs surgery after 1 week of 5-fu silva et al 20197 1 64 f lower extremity 1 photodynamic therapy for porokeratosis of mibelli 0.5% 5fu + 10% salicylic acid acitretin 0.6 1 mg/kg/day prior to 5-fu 1/1 at 8 weeks 12 months. no recurrence none ugwu et al 2020 1 94 m right lower extremity 5 surgery for scc on the right lower extremity 5% 5-fu cream daily for 2 weeks followed by 2 weeks without treatment for 4 months none 1/1 at 16 weeks 13 months. no recurrence none cr – complete response; pr – partial response; m – male; f – female; 1 hr – 1 hour; scc – squamous cell carcinoma skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 49 surgery were among the treatment options discussed with the patient, these approaches carried significant risk. for one, further surgical intervention (biopsy or excision) may have also incited more lesions. secondly, excision of multiple lesions would have resulted in large wounds on the lower extremity, which may have been further complicated by edema, delayed wound healing, and infection of the lower extremity. alternative non-surgical treatments also carried significant limitations. intralesional 5fluorouracil is painful to administer and requires repeated injections and office visits. topical 5-fluorouracil with zinc oxide wraps, also known as “chemo wraps," are tedious to apply properly, require repeated applications in the office, and result in significant discomfort 6. oral retinoids, which have been used alone or in combination of topical agents, carry significant risks, such as hypertriglyceridemia, bony pain, and transaminitis, require repeated laboratory monitoring, and can result in significant xerosis, all of which are significant risks in an elderly patient 2,7. topical 5-fluorouracil is an ideal medication: since the diseased area is visible to the patient, the medication can easily be applied and adverse events, namely irritant dermatitis, can be readily monitored. we utilized a cyclical application (2 weeks on, 2 weeks off) schedule to allow a period of recovery in between treatment intervals. to the best of our knowledge, this is the first case outlining the successful treatment of multiple, post-operative kas with topical 5fluorouracil. there are 43 published cases of kas treated with topical 5-fluorouracil (table 1) 7-12. the average age among the cohort was 68.8 years with a female to male ratio of 1.3. the most common tumor locations in patients were the head (51.1%), lower extremities (23.3%) and upper extremities (16.2%). the majority of reported lesions were solitary (98%). only 11.6% of patients developed kas following a surgical procedure. the most commonly used 5fluorouracil formulations were the 5% ointment (35%), 20% ointment (33%) and 5% cream (30%). one patient received acitretin for 1 month prior to initiating 5-fluorouracil treatment. the overall response rate was 95.3% (41/43 patients) with 90.7% (39/43) achieving complete response between 2 and 8 weeks of therapy. lesions with partial or no response to 5-fluorouracil were treated with surgical excision (2) or shave biopsy with electrodessication and curettage (1). one patient opted for mohs surgery after one week of 5-fluorouracil therapy. over the follow-up period which ranged from 2 to 18 months, there were no reported recurrences. this case highlights the successful and cyclical use of topical 5-fluorouracil in the treatment of post-operative eruptive kas. this conservative, non-invasive treatment is particularly suited for the very elderly and for post-traumatic kas. patient selection is critical, and close follow-up is recommended to refine the treatment schedule and interval between treatment courses. further systematic study into this phenomenon is needed to better outline treatment parameters and resolve the question of whether, under certain circumstances, eruptive kas may regress spontaneously. conflict of interest disclosures: none funding: none corresponding author: nour kibbi, md stanford dermatologic surgery 450 broadway 4th floor redwood city, ca 94063 phone: 650-725-5272 email: kibbi@stanford.edu skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 50 references: 1. chitwood k, etzkorn j, cohen g. topical and intralesional treatment of nonmelanoma skin cancer: efficacy and cost comparisons. dermatol surg. 2013;39(9):1306-1316. 2. goldberg lh, silapunt s, beyrau kk, peterson sr, friedman pm, alam m. keratoacanthoma as a postoperative complication of skin cancer excision. j am acad dermatol. 2004;50(5):753758. 3. clark ma, guitart j, gerami p, marks br, amin s, yoo ss. eruptive keratoacanthomatous atypical squamous proliferations (kasps) arising in skin graft sites. jaad case rep. 2015;1(5):274-276. 4. gewirtzman a, meirson dh, rabinovitz h. eruptive keratoacanthomas following carbon dioxide laser resurfacing. dermatol surg. 1999;25(8):666-668. 5. pattee sf, silvis ng. keratoacanthoma developing in sites of previous trauma: a report of two cases and review of the literature. j am acad dermatol. 2003;48(2 suppl):s35-38. 6. manalo if, lowe mc, nelson kc, chen sc. triple therapy with intralesional 5-fluorouracil, chemowraps, and acitretin: a well-tolerated option for treatment of widespread cutaneous squamous cell carcinomas on the legs. jaad case rep. 2019;5(12):1051-1054. 7. silva e, estebanez a, martin jm, monteagudo c, montesinos e. keratoacanthoma centrifugum marginatum after photodynamic therapy with good response to oral retinoids and topical 5fluorouracil. dermatol ther. 2019;32(4):e12988. 8. grupper c. treatment of keratoacanthomas by local applications of the 5-fluorouracil (5-fu) ointment. dermatologica. 1970;140:suppl 1:127+. 9. goette dk, odom rb, arrott jw, diakon nc, horn rt, jr. treatment of keratoacanthoma with topical application of fluorouracil. arch dermatol. 1982;118(5):309-311. 10. singal a, mohanty s, bhattacharya sn, baruah mc, singh n. unusual multiple keratoacanthoma in a child successfully treated with 5-fluorouracil. j dermatol. 1997;24(8):546-548. 11. thompson bj, ravits m, silvers dn. clinical efficacy of short contact topical 5-fluorouracil in the treatment of keratoacanthomas: a retrospective analysis. j clin aesthet dermatol. 2014;7(11):35-37. 12. gray rj, meland nb. topical 5-fluorouracil as primary therapy for keratoacanthoma. ann plast surg. 2000;44(1):82-85. présentation powerpoint acknowledgements and disclosures the study was funded by ucb pharma. this poster was originally presented as an oral presentation at the 28th eadv congress, 9–13 october 2019, madrid, spain. the authors would like to acknowledge jessica gamage phd cmpp, of imed comms, an ashfield company, for medical writing support that was funded by ucb pharma in accordance with gpp3 guidelines. ka papp reports consultant honoraria from abbvie, akros, amgen, arcutis, astellas, baxalta, boehringer ingelheim, bristol-myers squibb, canfite, celgene, coherus, dermira, dow pharma, eli lilly, forward pharma, galderma, genentech, janssen, kyowa hakko kirin, leo, merck (msd), merckserono, mitsubishi pharma, novartis, pfizer, prcl research, regeneron, roche, sanofi aventis/genzyme, sun pharma, takeda, ucb pharma, valeant/bausch health; speaker fees from abbvie, amgen, astellas, celgene, eli lilly, galderma, janssen, kyowa hakko kirin, leo, merck (msd), novartis, pfizer, sanofi aventis/genzyme, sun pharma, valeant/bausch health; investigator grants from abbvie, akros, allergan, amgen, anacor, arcutis, astellas, baxalta, boehringer ingelheim, bristol-myers squibb, canfite, celgene, coherus, dermira, dow pharma, eli lilly, galderma, genentech, gilead, glaxosmithkline, janssen, kyowa hakko kirin, leo, medimmune, merck (msd), merck-serono, moberg pharma, novartis, pfizer, prcl research, regeneron, roche, sanofi aventis/genzyme, sun pharma, takeda, ucb pharma, valeant/bausch health; advisory board honoraria from abbvie, amgen, astellas, boehringer ingelheim, bristol-myers squibb, celgene, dow pharma, eli lilly, galderma, janssen, merck (msd), novartis, pfizer, regeneron, sanofi aventis/genzyme, sun pharma, ucb pharma, valeant/bausch health; and other fees from abbvie, akros, amgen, anacor, boehringer ingelheim, celgene, coherus, eli lilly, janssen, kyowa hakko kirin, merck (msd), merck-serono, novartis, pfizer, regeneron, sanofi aventis/genzyme, sun pharma, valeant/bausch health. jf merola reports consultant honoraria from abbvie, almirall, celgene, eli lilly, glaxosmithkline, janssen, merck, novartis, samumed, sanofi regeneron, sun pharma, ucb pharma; investigator honoraria from biogen idec, celgene, incyte, novartis, pfizer, sanofi regeneron; and other financial benefit from abbvie. a gottlieb reports consultant/advisory board agreements/or speakers bureau agreements with abbvie, allergan, avotres therapeutics, beiersdorf, bristol-myers squibb, celgene, dermira, eli lilly, incyte, janssen, leo, novartis, reddy labs, sun pharmaceutical industries, ucb pharma, valeant, xbiotech; and research/educational grants from boehringer ingelheim, incyte, janssen, novartis, xbiotech, ucb pharma. cem griffiths reports advisory board honoraria from abbvie, almirall, celgene, eli lilly, galderma, janssen, novartis, pfizer, sandoz, ucb pharma; speaker honoraria from abbvie, almirall, bristol-meyers squibb, celgene, eli lilly, galderma, janssen, novartis, pfizer, sandoz, ucb pharma; and other grants from abbvie, celgene, eli lilly, janssen, leo, novartis, pfizer, sandoz, ucb pharma. kk harris, n cross and c madden are employees of ucb pharma. l peterson and c cioffi are employees and stockholders of ucb pharma. a blauvelt reports consultant and investigator fees from abbvie, aclaris, akros, allergan, almirall, amgen, arena, boehringer ingelheim, bristol-myers squibb, celgene, dermavant, dermira inc, eli lilly, flx bio, galderma, genentech/roche, glaxosmithkline, janssen, leo, meiji, merck sharp & dohme, novartis, pfizer, purdue pharma, regeneron, revance, sandoz, sanofi genzyme, sienna pharmaceuticals, sun pharmaceuticals, ucb pharma, valeant, vidac; and speaker fees from janssen, regeneron, sanofi genzyme. bimekizumab provides rapid and sustained improvements in quality of life that correlate with clinical outcomes in patients with moderate-to-severe plaque psoriasis: 60-week results from a randomized, double-blinded, phase 2b extension study kim a papp,1 joseph f merola,2 alice b gottlieb,3 christopher em griffiths,4 kristina k harris,5 nancy cross,6 luke peterson,6 christopher cioffi,7 andrew blauvelt8 synopsis ● bimekizumab, a monoclonal igg1 antibody that potently and selectively binds, and neutralizes, both il-17a and il-17f,1 provided rapid, substantial and sustainable clinical improvements in patients with moderate-to-severe plaque psoriasis in the 12-week be able 1 (nct02905006) and the 48-week be able 2 extension (nct03010527) studies, with no unexpected safety findings2–4 ● the disease burden of psoriasis extends beyond physical manifestations and can have a profound negative impact on quality of life (qol) ● a substantial proportion of patients with moderate to severe psoriasis experience impaired qol, including negative effects on emotional well-being and ability to perform everyday activities5–8 ● approximately 50% of patients with moderate-to-severe psoriasis have a dermatology life quality index (dlqi) score >10, indicating a very large effect on patient qol9 1probity medical research and k papp clinical research, waterloo, on, canada; 2harvard medical school, brigham and women's hospital, boston, ma, usa; 3department of dermatology, icahn school of medicine at mount sinai, new york, ny, usa; 4dermatology centre, university of manchester, manchester, uk; 5ucb pharma, hong kong, china; 6ucb pharma, raleigh, nc, usa; 7ucb pharma, brussels, belgium; 8oregon medical research center, portland, or, usa methods ● in be able 1, patients were randomized to placebo or bimekizumab 64 mg, 160 mg, 160 mg with a 320 mg loading dose (ld), 320 mg or 480 mg1 ● be able 1 responders (≥90% reduction in psoriasis area and severity index [pasi90] at week 12) randomized to placebo or bimekizumab every 4 weeks (q4w) 64 mg, 160 mg, or 160 mg (320 mg ld), continued the same treatment to week 60 (figure 1) ● patients completed the dlqi questionnaire throughout the treatment period – a dlqi score of 0/1 indicated no impact of psoriasis on diseasespecific hrqol ● to evaluate a possible correlation between clinical response and hrqol, patients achieving dlqi of 0/1 were grouped by absolute pasi (0, >0–<2, ≥2–<5, ≥5) at weeks 12 and 60 ● non-responder imputation (nri) and observed data are presented references 1. glatt s et al. br j clin pharmacol 2017;83:991–1001 2. papp ka et al. j am acad dermatol 2018:79:279–286 3. papp ka et al. eadv 2018 [e-poster p1978] 4. blauvelt a et al. aad 2019 (oral presentation op11180) 5. armstrong aw et al. plos one 2012;7(12):e52935 6. strober b et al. bmj open 2019;9(4):e027535 7. griffiths cem et al. br j dermatol 2018;179:173–181 8. korman nj et al. dermatol online j 2015;21(10):pii: 13030/qt1x16v3dg 9. augustin m et al. br j dermatol 2018;179:1385–1391. objective ● in this post-hoc qol analysis we evaluated the effect of bimekizumab on health-related qol (hrqol) in patients with moderate-to-severe psoriasis and correlation with clinical response over the 60-week treatment period conclusions • bimekizumab treatment resulted in rapid, substantial and sustained improvements in qol in patients with moderate-to-severe psoriasis – the majority of be able 1 responders achieved dlqi of 0 or 1 by week 12 and maintained responses up to week 60 • improvements in qol was associated with clinical response – patients with an absolute pasi of 0 were most frequently associated with high qol, with 79% and 95% achieving dlqi of 0 or 1 at weeks 12 and 60, respectively results ● patient demographics and baseline disease characteristics were balanced across treatment groups (table 1) presented at fall clinical dermatology conference® 2019 │las vegas, nv, usa │ october 17–20, 2019 bimekizumab 160 mg (responders)  160 mg; n=55 bimekizumab 160 mg (non-responders)  320 mg; n=14 n=42 n=39 n=43 bimekizumab 480 mg q4w bimekizumab 320 mg q4w bimekizumab 160 mg q4w (with 320 mg loading dose) bimekizumab 160 mg q4w bimekizumab 64 mg q4w placebo q4w be able 1 treatment period be able 2 treatment period baseline week 64 be able 1 week 12 / be able 2 baseline n=250 if <pasi75 at week 12 or later, withdraw from study treatment be able 1 / be able 2 week 60 / week 48 n=40 n=43 n=43 bimekizumab 64 mg (responders)  64 mg; n=15 bimekizumab 64 mg (non-responders)  160 mg; n=19 bimekizumab 320 mg (responders)  320 mg; n=33 bimekizumab 320 mg (non-responders)  320 mg; n=6 placebo (responders)  placebo; n=0 placebo (non-responders)  160 mg; n=37x bimekizumab 480 mg (non-responders)  320 mg; n=8 bimekizumab 480 mg (responders)  320 mg; n=30 response in be able 1 determined treatment allocation in be able 2: ≥pasi90 = responders <pasi90 = non-responders patients completed the dlqi questionnaire at baseline and throughout be able 1 and be able 2 treatment periods post-hoc analysis: association between clinical response (by absolute pasi) and hrqol was assessed figure 3. dlqi scores in pasi90 responders: bimekizumab provided rapid improvements in qol that were sustained to week 60 (nri) *bimekizumab 160 mg group includes bimekizumab 160 mg and 160 mg with 320 mg loading dose in be able 1 dlqi was assessed throughout be able 1 and be able 2 treatment periods; full analysis set nri bkz 64 mg  64 mg; n=15 bkz 160 mg  160 mg; n=55* bkz 480 mg  320 mg; n=30 bkz 320 mg  320 mg; n=33 0 20 40 60 80 100 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 p a s i9 0 r e s p o n d e rs a c h ie v in g d l q i 0 / 1 ( % ) 0 4 8 12 16 20 24 28 32 36 40 44 48 weeks from be able 1 / be able 2 baseline 93.3% 86.7% 78.8% 76.4% dlqi score of 0 or 1 indicates no impact of psoriasis on hrqol figure 4. percentage of patients achieving dlqi of 0 or 1 by absolute pasi at weeks 12 and 60 (pooled; observed) figure 1. be able 1 and be able 2 study design bimekizumab 64 mg q4w n=15 bimekizumab 160 mg q4w n=111 bimekizumab 320 mg q4w n=91 all patients n=217 age, years, mean (±sd) 44.5 (14.7) 44.5 (12.8) 43.5 (14.7) 44.1 (13.7) sex, male, n (%) 9 (60.0) 71 (64.0) 60 (65.9) 140 (64.5) weight, kg, mean (±sd) 85.2 (16.8) 88.4 (19.1) 90.3 (23.5) 89.0 (20.9) race, caucasian, n (%) 13 (86.7) 99 (89.2) 83 (91.2) 195 (89.9) prior systemic therapy, n (%) 13 (86.7) 77 (69.4) 67 (73.6) 157 (72.4) prior non-biologic systemic therapy 6 (40.0) 37 (33.3) 41 (45.1) 84 (38.7) prior biologic therapy 6 (40.0) 23 (20.7) 21 (23.1) 50 (23.0) prior anti-tnf therapy, n (%) 2 (13.3) 13 (11.7) 13 (14.3) 28 (12.9) disease duration, years, median (range) 13.9 (6.0–53.4) 15.0 (0–58.7) 15.0 (0.7–50.0) 15.0 (0–58.7) pasi, mean (±sd) 17.1 (4.5) 19.8 (7.0) 19.3 (6.6) 19.4 (6.7) iga score, n (%) 3 (moderate) 11 (73.3) 84 (75.7) 71 (78.0) 166 (76.5) 4 (severe) 4 (26.7) 27 (24.3) 20 (22.0) 51 (23.5) percentage bsa involvement, mean (±sd) 21.8 (9.5) 26.5 (14.8) 24.8 (12.7) 25.4 (13.6) bsa, body surface area; iga, investigator’s global assessment; sd, standard deviation; tnf, tumour necrosis factor; safety set p a s i9 0 r e s p o n s e , % placebo  160 mg; n=37 xbkz 64 mg  64 mg; n=15 bkz 160 mg  160 mg; n=55* bkz 480 mg  320 mg; n=30 bkz 320 mg  320 mg; n=33 n=39 n=83 n=43 n=43 be able 1 (week 12): all patients1 r e s p o n d e r ra te s , % be able 2 (weeks 12–60): be able 1 pasi90 responders3 bkz, bimekizumab *bimekizumab 160 mg group includes bimekizumab 160 mg and 160 mg with 320 mg loading dose in be able 1; full analysis set nri figure 2. phase 2 be able study: substantial proportions of patients achieved pasi90 at week 12, which was maintained to week 60 (nri) ● substantial proportions of patients achieved pasi90 at week 12, which was maintained to week 60 (figure 2) ● in be able 1 pasi90 responders, bimekizumab provided rapid improvements in qol (achieving dlqi of 0 or 1) at week 8 (figure 3) – the majority achieved dlqi 1 or 0 by week 12 – dlqi responses were maintained to week 60 (76–93%) ● in pasi90 non-responders, rapid improvements in qol were observed and maintained in patients re-assigned from placebo to bimekizumab 160 mg, with 84% of patients achieving dlqi of 0/1 at week 60 – across the other bimekizumab dose groups, dlqi of 0/1 was achieved by 50–71% of non-responders at week 60 ● in the pooled bimekizumab group, patients with an absolute pasi of 0 were most frequently associated with higher qol, with 79% and 95% achieving dlqi of 0/1 at weeks 12 and 60, respectively (figure 4) 46.2 71.1 79.1 72.1 0 20 40 60 80 100 bkz 64 mg bkz 160 mg bkz 320 mg bkz 480 mgbkz 160 mg bkz 64 mg bkz 320 mg bkz 480 mg table 1. demographics and baseline disease characteristics3 dlqi was assessed throughout be able 1 and be able 2 treatment periods; full analysis set observed data absolute pasi score ≥5 ≥2–<5 >0–<2 0 week 12 week 60 n=86 79.1% n=150 95.3% n=28 82.1% n=47 76.6% n=6 50.0% n=33 45.5% n=0 0.0% dlqi >1dlqi 0 or 1 n=51 17.5% 80–100% (nri) 0 20 40 60 80 100 12 16 20 24 28 32 36 40 44 48 52 56 60 weeks from be able 1 / be able 2 baseline 0 4 8 12 16 20 24 28 32 36 40 44 48 skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 68 short communications toluidine blue for extramammary paget’s disease in mohs micrographic surgery roxana mititelu, md1, claudia flores-echaiz, md, frcpc1, manish khanna, md, frcpc2 1mcgill university health centre, division of dermatology, montreal, qc, canada 2jewish general hospital, division of dermatology oncology, montreal, qc, canada extramammary paget’s disease (empd) is a rare skin malignancy that can pose a treatment challenge stemming from the difficulty of identifying tumor margins due to subclinical extension. as such, conventional surgical management has shown recurrence rates of 20-60% while with the use of mohs micrographic surgery (mms) lower recurrence rates (12.2%) can be achieved.1 in mms one limiting factor is the visualization of paget cells in frozen specimens stained with hematoxylin and eosin (h&e). furthermore, immunohistochemical stains are often not employed in the settings of mms due to significant start-up costs, long incubation times, difficulty with antibody reagent consistency and staining reproducibility.2 the presence of mucin in paget cells lends itself to be visualized with special stains other than h&e, including alcian blue, pas, mucicarmine, and toluidine blue.3 we present a case of empd treated with mms using toluidine blue. the patient was an otherwise healthy 68year-old white man who presented with a 3year history of a slow growing, pruritic lesion on the left groin. on clinical examination abstract introduction: we report an elderly gentleman with extramammary paget’s disease (empd) treated with mohs micrographic surgery (mms) using toluidine blue staining intraoperatively as to detect the paget’s cells. case presentation: an elderly man presented with an erythematous plaque on the left inguinal fold which showed in-situ empd on histopathological examination. investigations for secondary empd were negative and the patient was treated with mms. during mms, the specimens from the patient were stained using toluidine blue in order to detect the paget cells and to determine the appropriate negative margin. at 4 years follow up the patient is free of recurrence. conclusion: toluidine blue is a fast, user-friendly dye that can be used intraoperatively during mms as to detect paget cells and thus to determine the appropriate negative margin. introduction case presentation skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 69 figure 1. frozen section with h&e staining of empd (100x). figure 2. frozen section with toluidine blue staining of empd (100x). the paget cells show metachromasia making them easily detectable. skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 70 there was a 4.0 cm by 3.0 cm erythematous plaque in the left groin involving the inguinal folds and no lymphadenopathy. histopathological examination showed in situ proliferation of malignant glandular cells strongly positive for her2-neu and cytokeratin-7 consistent with in-situ empd. extensive work up to asses for secondary empd was negative. the patient was treated with mms requiring 4 stages with a final defect of 10.5 cm by 9.4 cm repaired by primary linear closure. during the mms the frozen sections were stained with toluidine blue which allowed for easy identification of the intraepidermal paget cells. figure 1 compares h&e staining versus figure 2 showing toluidine blue staining on the frozen sections. he is 4 years post-surgery and has no clinical evidence of recurrence. treatment of empd has traditionally been challenging due to high recurrence rates. mms may be the best alternative, but it still has its limitations as recurrence rates remain high. part of this may be related to inability to identify remnant tumor when inspecting fresh tissue specimens with h&e. this can be exemplified by cases where h&e biopsies are negative for empd while specimens stained with cytokeratin 7 reveal a positive diagnosis.4 immunological markers can increase sensitivity and specificity but are time consuming, and not easily available for mms. therefore, a non-immunohistochemical stain that may easily identify tumor could be better suited for the management of empd by mms. toluidine blue is a metachromatic stain highlighting the mucin in paget cells and allows for rapid identification of the cells in empd. another advantage of toluidine blue is its lower staining times.5 given our report, we propose this stain as a viable alternative for the management of empd by mms. however, our case has several limitations including being a single case report, and the lack of a direct comparison arm. further research including larger trials comparing the toluidine blue to the standard h&e is necessitated. conflict of interest disclosures: none funding: none corresponding author: roxana mititelu, md montreal general hospital 1650 cedar avenue, d6.245 montreal, qc, h3g 1a4 phone: 514-743-7724 email: roxana.mititelu@mail.mcgill.ca references: 1. bae jm, choi yy, kim h, et al. mohs micrographic surgery for extramammary paget disease: a pooled analysis of individual patient data. journal of the american academy of dermatology. 2013;68(4):632-637. doi:10.1016/j.jaad.2012.12.960 2. 2. petrie ms, hess s, benedetto a v. automated 15-minute cytokeratin 7 immunostaining protocol for extramammary paget’s disease in mohs micrographic surgery. dermatologic surgery. 2011;37(12):1811-1815. doi:10.1111/j.1524-4725.2011.02181.x 3. 3. kanitakis j. mammary and extramammary paget’s disease. journal of the european academy of dermatology and venereology. 2007;21(5):581-590. doi:10.1590/abd18064841.20153189 4. 4. hendi a, perdikis g, snow jl. unifocality of extramammary paget disease. journal of the american academy of dermatology. 2008;59(5):811-813. doi:10.1016/j.jaad.2008.08.006 5. 5. logan me, zaim mt. histologic stains in dermatopathology. journal of the american academy of dermatology. 1990;22(5):820-830. doi:10.1016/s0190-9622(08)81173-5 discussion hematology laboratory shift based on common terminology criteria in patients with advanced basal cell carcinoma receiving sonidegib 200 mg daily: results from the 42-month bolt study michael migden1, alexander guminski2,3,4, ralf gutzmer5, carmen loquai6, nicholas squittieri7, peter foley8,9,10 1university of texas md anderson cancer center, departments of dermatology, division of internal medicine, and head and neck surgery, division of surgery, houston, tx, usa; 2department of oncology, royal north shore hospital, st leonards, australia; 3melanoma institute australia, the university of sydney, sydney, australia; 4mater hospital, sydney, australia; 5skin cancer center hannover, department of dermatology, hannover medical school, hannover, germany; 6department of dermatology, university medical center mainz, mainz, germany; 7sun pharmaceutical industries, inc., princeton, nj, usa; 8department of dermatology, st vincent’s hospital melbourne, fitzroy, victoria, australia; 9the university of melbourne, parkville, victoria, australia; 10skin health institute inc, carlton, victoria, australia background • hedgehog inhibitors were developed to block aberrant hedgehog signaling found in the majority of sporadic basal cell carcinomas (bccs); inhibition of the hedgehog pathway is among the few treatment options available for patients with advanced bcc1,2 • sonidegib is a hedgehog inhibitor that selectively targets smoothened3 and is approved at a dose of 200 mg daily in the us, the eu, switzerland, and australia for the treatment of adult patients with locally advanced bcc (labcc) not amenable to curative surgery or radiation therapy3–6 — sonidegib 200 mg daily is also approved to treat metastatic bcc (mbcc) in switzerland and australia5,6 • through 42 months of the phase 2 bolt (basal cell carcinoma outcomes with lde225 [sonidegib] treatment) trial (nct01327053), sonidegib 200 mg daily demonstrated durable efficacy and consistent/ manageable toxicity7–10 • evaluation of safety parameters, such as hematology laboratory values in patients with advanced bcc provides valuable information on the tolerability and safety of sonidegib objective • to determine hematology laboratory abnormalities in patients receiving sonidegib 200 mg daily through 42 months of treatment for advanced bcc methods study design • bolt was a randomized, double-blind, phase 2 clinical trial conducted in 58 centers across 12 countries10 • eligible patients had either histologically confirmed labcc or mbcc, and were randomized 1:2 to receive sonidegib 200 or 800 mg orally daily, respectively (figure 1) figure 1. bolt study design patient population* • labcc (aggressive and nonaggressive) • mbcc sonidegib 200 mg/d‡ treatment sonidegib 800 mg/d‡ stratification† randomization (1:2) endpoints primary • orr (central review) by mrecist (labcc) or recist v1.1 (mbcc) key secondary • dor, cr (central review) other secondary • orr, dor (investigator review) • pfs, ttr (central and investigator review) • os, safety follow-up (after treatment discontinuation) • tumor response q8w during year 1 and then q12w until progression • subsequent anticancer therapy • aes until 30 days after last dose of sonidegib • survival follow-up q12w until death, lost to follow-up, or withdrawn consent (and at time of final analysis) *patients previously treated with sonidegib or other hhi were excluded. ‡stratification was based on stage, disease histology for patients with labcc (nonaggressive vs aggressive), and geographic region. †treatment was continued until disease progression, unacceptable toxicity, death, study termination, or withdrawal of consent. ae, adverse event; bcc, basal cell carcinoma; bolt, basal cell carcinoma outcomes with lde225 (sonidegib) treatment; cr, complete response; dor, duration of response; hhi, hedgehog inhibitor; labcc, locally advanced bcc; mbcc, metastatic bcc; mrecist, modified response evaluation criteria in solid tumors; orr, objective response rate; os, overall survival; pfs, progression-free survival; q8w, every 8 weeks; q12w, every 12 weeks; ttr, time to tumor response. assessments • the primary efficacy endpoint was objective response rate (orr) per central review (figure 2) • orr was defined as the proportion of patients with a confirmed best overall response (determined on consecutive assessments ≥ 4 weeks apart) of complete response or partial response figure 2. bolt study endpoints •os •safety •orr and dor per investigator review •pfs and ttr per central review other secondary dor and cr rates per central review according to mrecist (labcc) or recist v1.1 (mbcc) key secondary orr  best overall confirmed response of cr or pr per central review according to mrecist (labcc) or recist v1.1 (mbcc) primary bcc, basal cell carcinoma; bolt, basal cell carcinoma outcomes with lde225 (sonidegib) treatment; cr, complete response; dor, duration of response; labcc, locally advanced bcc; mbcc, metastatic bcc; mrecist, modified recist; orr, objective response rate; os, overall survival; pfs, progressionfree survival; pr, partial response; recist, response evaluation criteria in solid tumors; ttr, time to tumor response. • tumor response was evaluated by central review using modified response evaluation criteria in solid tumors (mrecist) for patients with labcc and recist v1.1 for patients with mbcc hematology assessments • hematology assessments were performed at screening, biweekly for 14 weeks, then every 4 weeks until week 77, and then followed as clinically indicated until end of treatment — assessments included hemoglobin, platelet counts, complete red blood cell counts, and total white blood cell counts — differential white blood cell counts included neutrophils, lymphocytes, monocytes, eosinophils, and basophils • hematology evaluations were performed by a central laboratory until week 182; following week 182, hematology assessments were conducted locally • abnormal laboratory values constituted adverse events (aes) if they fulfilled ≥1 of the following criteria: — induced clinical signs — considered clinically significant — required concomitant therapy or procedures — required changes in study treatment safety • safety assessments included ae monitoring and recording until 30 days after the last dose through regular monitoring of hematology, clinical chemistry, electrocardiograms, vital signs, and physical condition — aes were coded using the medical dictionary for regulatory activities terminology v19.0, and toxicity was assessed using the national cancer institute common terminology criteria for adverse events v4.0311 results patient demographics and baseline disease characteristics • at baseline, 48 (60.8%) of the 79 patients receiving sonidegib 200 mg daily were male (table 1) — the median age was 67 years table 1. baseline demographics and disease characteristics in patients receiving sonidegib 200 mg daily all patients (n = 79) age, years, median (range) 67 (25–92) sex, male 48 (60.8) ecog performance status 0 50 (63.3) 1 19 (24.1) 2 8 (10.1) unknown 2 (2.5) stage labcc 66 (83.5) mbcc 13 (16.5) histologic/cytologic subtype aggressive* 40 (50.6) nonaggressive† 38 (48.1) undetermined 1 (1.3) number of lesions 0 0 1 30 (38.0) ≥2 49 (62.0) prior antineoplastic therapy surgery 59 (74.7) radiotherapy 19 (24.1) data presented as n (%) unless otherwise indicated. *includes micronodular, infiltrative, multifocal, basosquamous, and sclerosing histological subtypes. †includes nodular and superficial histological subtypes. bcc, basal cell carcinoma; ecog, eastern cooperative oncology group; labcc, locally advanced bcc; mbcc, metastatic bcc. • at 42 months, orrs (95% confidence interval) in patients with labcc (n = 66) and mbcc (n = 13) receiving sonidegib 200 mg daily were 56.1% (43.3%–68.3%) and 7.7% (0.2%–36.0%), respectively (table 2) • disease control rate exceeded 90% in patients with both labcc and mbcc • sustained duration was confirmed, with a median duration of response of 26.1 months in patients with labcc table 2. efficacy outcomes per central review in patients receiving sonidegib 200 mg daily labcc (n = 66) mbcc (n = 13) orr, % 56.1 7.7 (95% ci) (43.3–68.3) (0.2–36.0) dcr, % 90.9 92.3 dor, median, months 26.1 24.0 (95% ci) (ne) (ne) pfs, median, months 22.1 13.1 (95% ci) (ne) (5.6–33.1) ttr, median, months 4.0 9.2 (95% ci) (3.8–5.6) (ne) results are for the intention-to-treat population. bcc, basal cell carcinoma; ci, confidence interval; dcr, disease control rate; dor, duration of response; labcc, locally advanced bcc; mbcc, metastatic bcc; ne, not estimable; orr, objective response rate; pfs, progression-free survival; ttr, time to tumor response. hematology assessments • in patients receiving sonidegib 200 mg daily, 24.1% of patients had grade 1 anemia and 3.8% of patients had grade 1 hyperhemoglobinemia (table 3) — zero patients had a grade 3 or 4 hemoglobin shift • overall, 16.5%, 8.9%, and 2.5% of patients had grade 1, 2, or 3 lymphocytopenia, respectively (table 3) • grade 1 or 2 neutropenia was detected in 6.3% and 1.3% of patients, respectively • leukocytosis was not observed in any patients table 3. hematologic shifts in patients receiving sonidegib 200 mg daily within normal limits grade 1 grade 2 grade 3 grade 4 anemia 54 (68.4) 19 (24.1) 6 (7.6) 0 0 hyperhemoglobinemia 76 (96.2) 3 (3.8) 0 0 0 leukopenia 74 (93.7) 4 (5.1) 1 (1.3) 0 0 neutropenia 73 (92.4) 5 (6.3) 1 (1.3) 0 0 lymphocytopenia 57 (72.2) 13 (16.5) 7 (8.9) 2 (2.5) 0 lymphocytosis 75 (94.9) 0 4 (5.1) 0 0 all data presented as n (%). • overall, 6.3% and 1.3% of patients had grade 1 or 4 thrombocytopenia, respectively (figure 3) — zero patients had a grade 2 or 3 shift in thrombocytes • 92.4% of patients had no shift in thrombocyte counts figure 3. hematology shifts in patients receiving sonidegib 200 mg daily within normal limits grade 1 grade 2 grade 3 grade 4 0 25 50 75 100 % o f p at ie nt s anemia hyperhemoglobinemia leukopenia neutropenia lymphocytopenia lymphocytosis thrombocytopenia safety and tolerability at 42 months • overall, the safety profile of sonidegib 200 mg daily was manageable and consistent with prior analyses9,10 • in patients receiving sonidegib 200 mg daily, the median duration of exposure was 11.0 months • overall, 54 (68.4%), 34 (43.0%), and 19 (24.1%) patients were exposed to sonidegib 200 mg daily for ≥8, ≥12, and ≥20 months, respectively • the majority of aes were grade 1–2 in severity • the most common all-grade aes in patients receiving sonidegib 200 mg daily were muscle spasms (54.4%), alopecia (49.4%), and dysgeusia (44.3%; figure 4) figure 4. adverse events reported in ≥20% of patients receiving sonidegib 200 mg daily percent of patients diarrhea fatigue nausea dysgeusia alopecia muscle spasm decreased appetite ck increased weight decreased 0 20 40 60 22.8 30.4 30.4 31.6 32.9 39.2 44.3 49.4 54.4 21.5 24.1 25.3 30.4 31.6 38.0 44.3 49.4 51.9 grade 1–2 grade 3–4 ck, creatine kinase. conclusions • through 42 months of treatment with sonidegib 200 mg daily, most patients experienced no hematology changes or grade 1 hematology shifts • overall safety findings at 42 months were consistent with observations at 30 months9 • overall, patients with labcc and mbcc receiving sonidegib 200 mg daily experienced consistent and robust efficacy and manageable tolerability references 1. cortes je, et al. cancer treat rev. 2019;76:41–50. 2. kim jys, et al. j am acad dermatol. 2018;78(3):540–59. 3. odomzo (sonidegib capsules). full prescribing information. sun pharmaceutical industries, inc., cranbury, nj, usa. 4. european medicines agency. summary of product characteristics, wc500188762. http://www. ema.europa.eu/docs/en_gb/document_library/epar_-_product_information/human/002839/wc500192970. pdf. 5. swissmedic, authorization number 65065, 2015. https://www.swissmedic.ch/swissmedic/de/home/ humanarzneimittel/authorisations/new-medicines/odomzo--200mg--kapseln--sonidegibum-.html. 6. australian government department of health, artg 292262. https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/ pdf?openagent&id=cp-2017-pi-02511-1&d=2018030216114622483. 7. dummer r, et al. br j dermatol. 2020;182(6):1369–78. 8. dummer r, et al. j am acad dermatol. 2016;75(1):113–25.e115. 9. lear jt, et al. j eur acad dermatol venereol. 2018;32(3):372–81. 10. migden mr, et al. lancet oncol. 2015;16(6):716–28. 11. health udo, services h. common terminology criteria for adverse events (ctcae) version 4.0. national institutes of health, national cancer institute. 2009;4(03). acknowledgements medical writing and editorial support were provided by alex milliken, phd, of alphabiocom, llc, and funded by sun pharma. disclosures mm participated in advisory boards and received honoraria from genentech, novartis, sun pharma, and regeneron. ag has participated on advisory boards for bristol-myers squibb, pfizer, and sanofi; received honoraria from novartis; and received travel support from astellas and bristol-myers squibb. rg serves as a consultant to almirall, amgen, bristol-myers squibb, merck serono, merck sharp & dohme, novartis, pfizer, pierre fabre, roche, sanofi genzyme, sun pharma, and 4sc, has received travel grants and honoraria for lectures from almirall, amgen, bristol-myers squibb, merck serono, merck sharp & dohme, novartis, pierre fabre, roche, and sun pharma, and received research funding from amgen, johnson & johnson, merck serono, and novartis. cl acted as a speaker for, participated in an advisory board for, and received honoraria from bristol-myers squibb, roche, novartis, and merck sharp & dohme. ns is an employee of sun pharmaceutical industries, inc. pf has participated in clinical trials (investigator), been on an advisory board, been a consultant, received speaker’s bureau/honoraria, and/or received research and/or travel grants from abbvie, akaal, amgen, arcutis, aslan, astrazeneca, bristol-myers squibb, boehringer ingelheim, botanix, celgene, celtaxsys, csl, cutanea, dermira, eli lilly and company, galderma, geneseq, genetech, gsk, hexima, janssen, leo pharma, mayne pharma, medimmune, merck, novartis, pfizer, regeneron, reistone, roche, sanofi, sun pharma, ucb, and valeant. microsoft word july 2020 dh 797 proof final.docx skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 393 dermatologic history ken hashimoto – a pioneer in dermatological electron microscopy reem kashlan, mph1, joshua m. brady, bs1, meena moossavi, md, mph1 1wayne state university school of medicine ken hashimoto was born in niigata, japan on june 19, 1931. hashimoto, a fulbright scholar, received his medical degree from niigata university medical school and dermatological training at the university of maryland and massachusetts general hospital.1 hashimoto subsequently established and was chair of the dermatology program at wright state university before coming to wayne state university (wsu) in 1980.1,2 hashimoto held his position as professor and chairman of wsu until his retirement in 2000, becoming the first and only japanese national to head an american dermatological department at that time.1 hashimoto’s proficiency with the electron microscope and extensive knowledge of histochemistry was vital to the understanding of many diseases. one of the most important applications of his skills was an electron microscopy study outlining the specific dermatological histopathology of angiokeratoma corporis diffusum, also known as fabry disease.2 he further utilized his skills to expand on many other dermatological pathologies such as kaposi’s sarcoma and appendage tumors of the skin.1 notably, hashimoto was involved with the discovery of two rare dermatological diseases: transient bullous dermolysis of the newborn and congenital self-healing reticulohistiocytosis, also known as hashimoto-pritzker disease.1 during his academic career, hashimoto wrote 384 professional papers, 39 book chapters, and 8 books.3 as a professor and program director, hashimoto excelled as a mentor, training 100 resident physicians and 40 research fellows.3 he also focused his efforts on easing the transition of japanese dermatology students coming to the united skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 394 states for postgraduate training.1 prior to his retirement, hashimoto created the herman pinkus endowed chair in 1999, which allowed the wsu department of dermatology to remain an independent department. in 2007, ken hashimoto and his wife established the dr. ken hashimoto and noriko hashimoto endowed chair at wsu to promote research and ensure a lasting legacy of education.3 hashimoto’s countless contributions left a lasting impression on the field of dermatology, where his academic achievements will continue to impact future generations of dermatologists. conflict of interest disclosures: none funding: none corresponding author: reem kashlan, mph 540 e. canfield ave, detroit, mi, 48201 phone: 248-410-3289 email: reem.kaslan2@med.wayne.edu references: 1. crissey jt, parish lc, holubar k. chapter 17: recent times. in: historical atlas of dermatology and dermatologists. parthenon pub. group; 2002:179-180. 2. hashimoto k, gross bg, lever wf. angiokeratoma corporis diffusum (fabry). histochemical and electron microscopic studies of the skin. j invest dermatol. 1965;44:119-128. http://www.ncbi.nlm.nih.gov/pubmed/14258908. accessed september 25, 2019. 3. former dermatology department chair’s bequest creates endowed chair school of medicine news wayne state university. https://today.wayne.edu/medicine/news/2008/10/ 08/former-dermatology-department-chairsbequest-creates-endowed-chair-25192. published 10/08/2008. ce arrowitz,1 li jiang,2 pd hino,2 mj babcock,3 tm weber1 1beiersdorf inc., wilton, ct; 2thomas j stephens & associates, richardson, tx; 3colorado springs dermatology clinic, colorado springs, co introduction conclusions reference objective methods a comparison of efficacy among therapeutic moisturizing creams u xerosis is a highly prevalent condition, with moisturizers being the mainstay of treatment1 u there are many available moisturizing cream formulations to choose from, which vary in composition and efficacy u moisturization superiority can only be established from controlled, head-to-head comparative trial results u the two studies reported here compared a single moisturizing cream formulation versus two market-competitor formulations when used by subjects with dry skin on the lower legs results u all subjects enrolled completed the study (table 1) u all three moisturizing creams significantly improved hydration of dry skin after 10 days of daily use; this was maintained for 5 days after treatment was discontinued u in study 1, mca demonstrated superiority to mcb in improving skin hydration as well as reducing skin flakiness due to dry skin u in study 2, mca significantly improved skin hydration compared with mcc at day 10. additionally, mca improved tewl significantly after 10 days compared with baseline, while mcc did not u these results suggest that mca outperformed mcb and mcc in alleviating dry skin on the lower legs u these studies demonstrated that all three products would be suitable for the treatment of xerosis; however, mca demonstrated superior efficacy as a therapeutic moisturizer 1. draelos zd. cutis. 2013;91:308–314. u to compare the efficacy of three therapeutic moisturizers in improving dry skin u two double-blind, comparative, split-body studies were conducted study 1 subjects u 35 subjects aged 18–65 years with mild to severe xerosis on lower legs products u eucerin advanced repair cream (beiersdorf inc., wilton, ct; moisturizing cream a [mca]) u cetaphil moisturizing cream (galderma, fort worth, tx; moisturizing cream b [mcb]) study 2 subjects u 33 subjects aged 16–65 years with mild to severe xerosis on lower legs products u moisturizing cream a (mca) u cerave moisturizing cream (l’oréal, new york, ny; moisturizing cream c [mcc]) study design u each subject served as their own comparator (split-body trial design) u products were randomly assigned to each lower leg and applied once daily for 10 days u subjects discontinued product use at day 10 and participated in a 5-day regression phase assessments u expert clinical grading (dryness, roughness, flaking), skin hydration, and transepidermal water loss (tewl) at baseline, day 10, and regression day 5 – clinical grading used a scale of 0 (none) to 9 (severe) u clinical grading parameters were statistically tested using wilcoxon signed-rank test; corneometer and tewl comparisons were tested using paired t-test sponsorship: research sponsored by beiersdorf inc., wilton, ct regression phase (5 days) treatments applied daily (10 days) treatment discontinued baseline day 10 r day 5assessments table 1. baseline demographics study 1 (n=35) study 2 (n=33) sex, n (%) female 23 (65.7) 21 (63.6) male 12 (34.3) 12 (36.4) fitzpatrick skin type, n (%) i 10 (28.6) 0 ii 2 (5.7) 7 (21.2) iii 4 (11.4) 17 (51.5) iv 18 (51.4) 4 (12.1) v 1 (2.9) 5 (15.2) 0 20 40 60 80 100 day 10 r day 5 0 20 40 60 80 100 day 10 r day 5 study 1 study 2 a,c a a b a,c a a a,d m e a n c h a n g e f ro m b a se li n e ( % ) m e a n c h a n g e f ro m b a se li n e ( % ) mca mcb mca mcc ap<0.001 vs baseline; bp=0.003 vs baseline; cp<0.001 in favor of mca; dp=0.009 in favor of mca figure 1. skin hydration improvement at day 10, and 5 days after completion of treatment (regression day 5) skin hydration measured using a corneometer 0 1 2 3 4 5 6 baseline day 10 r day 5 baseline day 10 r day 5 baseline day 10 r day 5 baseline day 10 r day 5 baseline day 10 r day 5 baseline day 10 r day 5 0 1 2 3 4 5 6a. dryness b. roughness c li n ic a l g ra d in g s co re c li n ic a l g ra d in g s co re a a a a a a aa 0 1 2 3 4 5 6 mca mcb mca mcc c. flaking c li n ic a l g ra d in g s co re a,b a a,b a 0 1 2 3 4 5 6 0 1 2 3 4 5 6 d. dryness e. roughness study 1 study 2 c li n ic a l g ra d in g s co re c li n ic a l g ra d in g s co re a a a a,b a a a a 0 1 2 3 4 5 6 f. flaking c li n ic a l g ra d in g s co re a a a,b a ap<0.001 vs baseline; bp≤0.01 vs mcb ap≤0.001 vs baseline; bp≤0.01 vs mcc figure 3. clinical grading of dryness (a, d), roughness (b, e), and flaking (c, f) symptoms were graded on a 0–9 scale (0 = none, 9 = severe) at baseline, day 10, and 5 days after completion of treatment (regression day 5). r, regression −8 −7 −6 −5 −4 −3 −2 −1 0 day 10 r day 5 −12 −10 −8 −6 −4 −2 0 day 10 r day 5 study 1 study 2 a m e a n c h a n g e f ro m b a se li n e ( % ) m e a n c h a n g e f ro m b a se li n e ( % ) ap<0.05 vs baseline mca mcb mca mcc figure 2. transepidermal water loss (tewl) improvement at day 10, and 5 days after completion of treatment (regression day 5) increased tewl is an indication of a disrupted barrier function; decreased tewl indicates improvement in barrier function. r, regression; tewl, transepidermal water loss u corneometer results indicated that all three test products statistically improved skin hydration after 10 days of daily use (figure 1) u mca showed statistically greater improvements in skin hydration compared with mcb and mcc at day 10, and compared with mcb 5 days after discontinuation of product u in study 1, no significant changes in tewl were observed for either mca or mcb at either time point (figure 2) u mca significantly improved tewl after 10 days compared with baseline in study 2. mcc did not significantly improve tewl relative to baseline (figure 2) u clinical grading in study 1 demonstrated that both mca and mcb significantly improved dryness, roughness, and flaking of the lower legs after 10 days, which was maintained 5 days after discontinuation of treatment (p<0.001) (figure 3 a–c) u mca significantly improved flaking compared with mcb (p<0.05) u clinical grading in study 2 showed that both mca and mcc significantly improved all three parameters from baseline and maintained these improvements 5 days after discontinuation (p≤0.001) (figure 3 d–e) u mca showed significantly greater maintenance of improvements in dryness and flaking at regression day 5 compared with mcc (p<0.01) long-term efficacy, safety, and patient-reported outcomes in a phase 2 study of brodalumab mark lebwohl,1 andrew blauvelt,2 alan menter,3 kim papp,4 abby jacobson5 1icahn school of medicine at mount sinai, new york, ny, usa; 2oregon medical research center, portland, or, usa; 3baylor university medical center, dallas, tx, usa; 4probity medical research and k. papp clinical research, waterloo, on, canada; 5ortho dermatologics (a division of bausch health us, llc), bridgewater, nj, usa 39th annual fall clinical dermatology conference® for dermatologists • october 17-20, 2019 • las vegas, nv introduction • brodalumab is a fully human anti–interleukin-17 receptor a monoclonal antibody approved for the treatment of moderate-to-severe plaque psoriasis • brodalumab demonstrated rapid and robust levels of skin clearance in a 12-week, double-blind, phase 2 study in patients with psoriasis1,2 objective • to evaluate the long-term efficacy and safety of brodalumab in an open-label extension (ole) of the phase 2 study methods • in the parent study, patients were randomized to brodalumab (70, 140, 210, or 280 mg) or placebo for 12 weeks1 • all patients in the ole initially received brodalumab 210 mg every 2 weeks (q2w) – dose reduction to brodalumab 140 mg q2w was later allowed in patients weighing ≤100 kg, along with a subsequent dose increase to brodalumab 210 mg q2w in patients with an inadequate response to brodalumab 140 mg q2w • efficacy was assessed by psoriasis area and severity index 75% improvement response (pasi 75) and pasi 100 (observed data analysis) – efficacy data were analyzed at weeks 12, 48, 96, 168, 216, and 264 • other assessments included the percentage of patients with a dermatology life quality index (dlqi) score of 0 or 1 (“dlqi responder”) • safety was reviewed in all patients who received ≥1 dose of brodalumab using the incidence of treatment-emergent adverse events (teaes) and the exposure-adjusted incidence of teaes results patient population • a total of 181 patients (117 men and 64 women; mean [standard deviation] age, 42.7 [12.2] years; 90% white) entered the ole; 107 patients had an efficacy evaluation at week 264 • median duration of brodalumab exposure was 264 (interquartile range, 200-274) weeks efficacy • efficacy with brodalumab was maintained from week 12 up to week 264, with pasi 75 responses consistently ≥80% and pasi 100 responses consistently ≥40% (figure 1) – there was a decrease in response at week 264 (final study visit), when patients had been off treatment for ≥6 weeks patient-reported outcomes • the percentage of patients receiving brodalumab who had a dlqi score of 0 or 1 was 83.9% at week 12 and 68.4% at week 264 (figure 2) • a greater percentage of patients with pasi 100 responses had a dlqi score of 0 or 1 at week 264 (96.4% [27 of 28 patients]) than those with pasi 90 to <100 responses (85.7% [6 of 7 patients]) or pasi 75 to <90 responses (40.0% [2 of 5 patients]; figure 3) safety • no new safety signals emerged in the ole period • over all study years, teaes occurred in 177 patients; grade ≥3 teaes occurred in 41 patients (23%), and 29 patients (16%) had ≥1 serious teae – the most common teaes included nasopharyngitis, upper respiratory tract infection, and arthralgia (29%, 24%, and 20% of patients, respectively) • the exposure-adjusted event rate per 100 patient-years (number of events/total patient-years of exposure through end of study × 100) of teaes generally decreased over time (table 1) – the most frequent adverse events of interest included nervous system disorder, injection site reaction, psychiatric disorder (depression, suicidal ideation), and oropharyngeal candidiasis acknowledgments: the brodalumab clinical study program was sponsored by amgen/astrazeneca and this analysis was performed by amgen/astrazeneca. medical writing support was provided by medthink scicom under the direction of the authors and was funded by ortho dermatologics. ortho dermatologics is a division of bausch health us, llc. previous presentation information: data in this poster were previously presented at maui derm for dermatologists, january 26-30, 2019, maui, hi and 43rd annual hawaii dermatology seminar®, february 17-22, 2019, the big island, hi. references: 1. papp et al. n engl j med. 2012;366:1181-1189. 2. papp et al. j am acad dermatol. 2014;71:1183-1190. conclusions • brodalumab demonstrated high levels of skin clearance efficacy, improved dermatology quality of life scores, and was well tolerated through ~5 years of long-term treatment • complete skin clearance (pasi 100) with brodalumab was associated with improved quality of life relative to high levels of efficacy without complete skin clearance (pasi 75 to <100) © 2019. all rights reserved. n= 106131141153165175 95.4 93.3 89.5 92.9 92.4 84.0 62.9 61.8 52.9 59.6 63.4 43.4 0 20 40 60 80 100 12 48 96 168 216 264 pasi 75 patients off treatmenta pasi 100 weeks at week 123, 17% of patients had dose increased back to 210 mg q2w because of inadequate response r es po nd er s, % at week 59, 65% of patients had dose decreased from 210 to 140 mg q2w figure 1. rate of skin clearance response by pasi 75 and pasi 100 in patients who received any dose of brodalumab through week 264. n, number of patients who had a valid measurement value at the specified week; pasi 75 and 100, psoriasis area and severity index 75% and 100% improvement response. observed data analysis. aat week 264, patients had been off treatment for ≥6 weeks. n= 106131141153165175 83.9 82.8 75.5 78.6 83.1 68.4 0 20 40 60 80 100 12 48 96 168 216 264 patients off treatmenta weeks at week 123, 17% of patients had dose increased back to 210 mg q2w because of inadequate response r es po nd er s, % at week 59, 65% of patients had dose decreased from 210 to 140 mg q2w figure 2. percentage of dlqi responders (defined as patients with dlqi score of 0 or 1). dlqi, dermatology life quality index; n, number of patients who had a valid measurement value at the specified week. error bars are the 95% confidence interval. aat week 264, patients had been off treatment for ≥6 weeks. n= 2875941822 50.0 83.3 94.7 0 20 40 60 80 100 pasi 75 to <90 pasi 90 to <100 pasi 100 r es po nd er s, % 40.0 85.7 96.4 week 264aweek 12 figure 3. dlqi responders (defined as patients with dlqi score of 0 or 1) stratified by skin clearance response. dlqi, dermatology life quality index; n, number of patients who had a valid measurement value at the specified week. error bars are the 95% confidence interval. aat week 264, patients had been off treatment for ≥6 weeks. table 1. exposure-adjusted event rates of teaes among all patients who received any dose of brodalumab year 1 (n=181) year 2 (n=181) year 3 (n=181) year 4 (n=181) year 5 (n=181) year 6 (n=181) total py of exposure 172.9 330.1 475.2 611.0 725.7 731.7 number of teaes (exposure-adjusted event rate per 100 py)a all teaes 748 (432.6) 1154 (349.6) 1373 (288.9) 1565 (256.1) 1750 (241.1) 1770 (241.9) grade ≥2 380 (219.8) 593 (179.6) 733 (154.3) 863 (141.2) 997 (137.4) 1014 (138.6) grade ≥3 18 (10.4) 29 (8.8) 37 (7.8) 49 (8.0) 59 (8.1) 62 (8.5) serious teaes 13 (7.5) 18 (5.5) 22 (4.6) 31 (5.1) 40 (5.5) 41 (5.6) teaes of interest nervous system disorder 29 (16.8) 51 (15.4) 62 (13.0) 78 (12.8) 90 (12.4) 91 (12.4) injection site reaction 28 (16.2) 38 (11.5) 40 (8.4) 40 (6.5) 41 (5.6) 41 (5.6) psychiatric disorder 19 (11.0) 27 (8.2) 32 (6.7) 44 (7.2) 49 (6.8) 49 (6.7) oropharyngeal candidiasis 17 (9.8) 23 (7.0) 28 (5.9) 34 (5.6) 41 (5.6) 41 (5.6) hypersensitivity event 8 (4.6) 12 (3.6) 12 (2.5) 12 (2.0) 12 (1.7) 12 (1.6) depression 4 (2.3) 4 (1.2) 6 (1.3) 7 (1.1) 9 (1.2) 9 (1.2) serious infectious episode 4 (2.3) 6 (1.8) 6 (1.3) 7 (1.1) 8 (1.1) 8 (1.1) ischemic heart disease 0 (0.0) 0 (0.0) 1 (0.2) 4 (0.7) 7 (1.0) 7 (1.0) neutropenia 1 (0.6) 1 (0.3) 1 (0.2) 1 (0.2) 1 (0.1) 1 (0.1) suicide self-injury 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (0.1) 1 (0.1) ischemic cerebrovascular event 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) crohn’s disease 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) py, patient-years; teae, treatment-emergent adverse event. multiple occurrences of the same event for a patient are counted as multiple events. aexposure-adjusted event rate per 100 py calculated as number of events/total py of exposure through end of study × 100. trajectories for scalp hair regrowth in patients with severe alopecia areata treated with baricitinib study was sponsored by eli lilly and company, under license from incyte corporationwinter clinical dermatology conference; hawaii, usa; january 13-18, 2023 key results disclosures ■ bk has served on advisory boards and/or is a consultant and/or is a clinical trial investigator for abbvie, altrubio inc, almirall, anaptysbio, arena pharmaceuticals, bioniz therapeutics, bristolmeyers squibb, concert pharmaceuticals inc, equillium, horizon therapeutics, eli lilly and company, incyte corp, janssen pharmaceuticals, leo pharma, otsuka/visterra inc, pfizer inc, regeneron, sanofi genzyme, twi biotechnology inc, and viela bio. he is on speaker bureaus for abbvie, eli lilly and company, incyte corp, pfizer inc, regeneron and sanofi genzyme. js has received travel reimbursement and speaking honoraria from eli lilly and company. mo has received lecture fees from eli lilly co. and advisory fees from eli lilly co., pfizer inc., janssen pharmaceutical kk.(japan), taisho pharmaceutical co, and rohto pharmaceutical co. and grants/research funds form shiseido co., maruho co., and sun pharma japan ltd. ae has received research funding from pfizer, eli lilly, novartis, bristol-myers squibb, abbvie, janssen pharmaceuticals, boehringer ingelheim, the danish national psoriasis foundation, the simon spies foundation, and the kgl hofbundtmager aage bang foundation, and honoraria as consultant and/or speaker from abbvie, almirall, leo pharma, zuellig pharma ltd., galápagos nv, sun pharmaceuticals, samsung bioepis co., ltd., pfizer, eli lilly and company, novartis, union therapeutics, galderma, dermavant, ucb, mylan, bristol-myers squibb, mcneil consumer healthcare, horizon therapeutics, boehringer ingelheim, and janssen pharmaceuticals. rs reported serving as a consultant or paid speaker for or participating in clinical trials sponsored by leo, pharma, amgen, inc, novartis pharmaceuticals corporation, merck & co, celgene corporation, coherus biosciences, janssen global services, llc, regeneron pharmaceuticals inc, medimmune, llc, glaxosmithkline, cutanea, samson clinical, boehringer ingelheim, pfizer, inc, merck sharpe & dohme, oncobiologics, inc, f. hoffman–la roche, ltd, eli lilly and company, and bayer ag and is serving as the current president of the australasian hair and wool research society. yd, yfc, wsw, yd, and ns are employees and shareholders of eli lilly and company. ■ this study previously presented at the world congress for hair research 2022, melbourne australia, 18 – 21 november 2022 trajectories for scalp hair regrowth in patients with severe alopecia areata treated with baricitinib brett king1, jerry shapiro2, manabu ohyama3, alexander egeberg4, yves dutronc5, yun-fei chen5, wen-shuo wu5, yuxin ding5, najwa somani5, rodney sinclair6 1yale school of medicine, connecticut, usa, 2new york university langone health, new york, usa, 3department of dermatology, kyorin university faculty of medicine, tokyo, japan, 4bispebjerg hospital, copenhagen, denmark, 5eli lilly and company, indianapolis, usa, 6university of melbourne, melbourne, australia background ■ alopecia areata (aa) is a chronic autoimmune disorder characterized by unpredictable hair loss, that can affect any hair-bearing area.1 ■ the oral janus kinase (jak)1/jak2 inhibitor baricitinib has demonstrated efficacy for patients with severe aa,2,3 and has been approved for the treatment of severe aa in various regions including the usa, eu, and japan. ■ little is known about the overall pattern of clinical response to treatment of patients with severe aa. such information will be important to guide health care providers and patients seeking treatment. objective ■ this post hoc analysis of integrated data from two phase 3 trials (braveaa1 [nct03570749] and brave-aa2 [nct03899259]) describes trajectories of clinical response in patients with severe aa treated with baricitinib 2mg or 4mg over 52 weeks. conclusions ■ these analyses revealed three response patterns among patients with severe aa who achieved salt30 on baricitinib at any point within 52 weeks: early, gradual and late. ■ these findings can help to inform the treatment expectations for scalp hair regrowth as they suggest that baseline disease characteristics (severity and duration of current episode ) may factor into a patient’s trajectory of response. ■ longer treatment duration may be needed for some patients to assess the full impact of treatment on scalp hair regrowth. abbreviations aa=alopecia areata; bari=baricitinib; pbo=placebo; qd=once daily; salt=severity of alopecia tool; w=week; gmm=growth mixture modelling; salt≤20 = severity of alopecia tool score of less than or equal to 20; salt50 = severity of alopecia tool score 50% improvement from baseline; salt30 = severity of alopecia tool score 30% improvement from baseline; salt50 = severity of alopecia tool score 50% improvement from baseline references 1. pratt c, et al. nat rev dis primers. 2017;3:17011. 2. king b, et al. n engl j med 2022; 386:1687-1699. 3. king b, et al. j am acad dermatol. 2021;85:847-853. methods key eligibility criteria ■ male or female ≥18 years old; ≤60 years for males and ≤70 years for females ■ hair loss involving ≥50% of the scalp, as measured by the salt score ■ current episode of aa >6 months to <8 yearsc ■ no spontaneous improvement in the 6 months prior to screening ■ no concomitant treatments for aad statistical analyses ■ the full analysis set for patients randomized to 2mg or 4mg baricitinib was considered in these analyses. ■ data were censored after permanent study drug discontinuation or if collected remotely due to the covid-19 pandemic. ■ non-responder imputation was applied to binary endpoints (i.e., salt score ≤20, salt50) for missing data. study designa, brave-aa1 and brave-aa2 ■ non-responders were defined as having never reached at least a 30% improvement in salt score from baseline (salt30)* within 52 weeks of treatment with 2mg or 4mg baricitinib. ■ for patients who achieved salt30 at any point within 52 weeks, a machine-learning growth mixture model (gmm) was applied to cluster patients into response pattern subgroups based on salt score percent change from baseline. ■ for each response pattern, the following outcomes were analyzed: – proportion of patients achieving the brave-aa1/2 primary endpoint of salt score ≤20 (≤20% scalp hair loss), and – proportion of patients achieving ≥50% improvement from baseline in salt score (salt50). results scan or click the qr code or use this url (https://lillyscience.lilly.com/congress/ wcdc2023) for a list of all lilly content presented at the congress. other company and product names are trademarks of their respective owners. *salt30 threshold was used during the phase ii dose-decision process3 a figure is not the full study design, but only the first 52 weeks of both trials; b patients randomized to bari (4-mg or 2-mg qd) at baseline retained their treatment allocation through w52, whereas pbo non-responders were rescued at w36; c patients who had aa for ≥8 years could be enrolled if episodes of regrowth (spontaneous or under treatment) had been observed on the affected areas over the past 8 years; d oral/topical minoxidil or finasteride were allowed if on stable dose for 12 months and bimatoprost ophthalmic solution was allowed if on stable dose for 8 weeks methods the thin blue lines indicate individual patients, the thick blue lines are the smoothing lines using local polynomial regression fitting, and the blue dotted lines indicates a 30% improvement from baseline in salt score (salt30). data were censored after permanent study drug discontinuation or data collected at remote visits due to the covid-19 pandemic. identification of response patterns based on salt score percent change from baseline among 4mg-treated patients identification of response patterns based on salt score percent change from baseline among 2mg-treated patients the red lines indicate individual patients, the thick purple lines are the smoothing lines using local polynomial regression fitting, and the blue dotted line indicates a 30% improvement from baseline in salt score (salt30). data were censored after permanent study drug discontinuation or data collected at remote visits due to the covid-19 pandemic. data were censored after permanent study drug discontinuation or data collected at remote visits due to the covid-19 pandemic. non-responder imputation (nri) was applied to missing and censored data. proportion of 4mg-treated patients who achieved a ≥50% improvement from baseline in salt score over 52 weeks in different response pattern subgroups data were censored after permanent study drug discontinuation or data collected at remote visits due to the covid-19 pandemic. non-responder imputation (nri) was applied to missing and censored data. data were censored after permanent study drug discontinuation or data collected at remote visits due to the covid-19 pandemic. non-responder imputation (nri) was applied to missing and censored data. proportion of 2mg-treated patients who achieved a salt score ≤20 response over 52 weeks in different response pattern subgroups proportion of 2mg-treated patients who achieved a ≥50% improvement from baseline in salt score over 52 weeks in different response pattern subgroups data were censored after permanent study drug discontinuation or data collected at remote visits due to the covid-19 pandemic. non-responder imputation (nri) was applied to missing and censored data. baseline aa severity and duration of current episode influence the pattern of clinical response ■ growth mixture modelling revealed that 2mg or 4mg baricitinib-treated patients with severe aa clustered into response pattern groups based on time to onset of a salt30 response: ■ as reported previously, overall higher response rate was observed with baricitinib 4mg vs. 2mg, particularly when considering early and gradual responders. ■ 48% and 28% of 4 mg and 2 mg-treated patients respectively, were early and gradual responders. – approximately 90% of early and gradual responders achieved salt50 by week 52, regardless of dose. ■ 21% and 23% of 4mg and 2mg-treated patients, respectively, experienced a delayed (late) response (>36 weeks). – approximately 40% of delayed responders achieved salt50 at week 52, regardless of dose. ■ baseline severity and duration of current episode are associated with response pattern – early response was more frequent among patients with severe aa (salt score 50-94) compared to those with very severe aa (salt score 95-100). – longer duration of current aa episode (≥4 years) and very severe aa (salt score 95-100) were more commonly observed amongst non-responders. parameter 2mg (n=340) 4mg (n=515) nonresponders early response gradual response late response nonresponder s early respons e gradual response late response 166/340 (49%) 31/340 (9%) 64/340 (19%) 79/340 (23%) 160/515 (31%) 102/515 (20%) 143/515 (28%) 110/515 (21%) age mean (sd) 38.9 (13.0) 36.7 (10.8) 40.4 (12.1) 36.4 (13.8) 37.1 (13.2) 37.6 (13.1) 36.9 (12.4) 36.8 (13.6) gender female (%) 106 (63.9%) 20 (64.5%) 42 (65.6%) 44 (55.7%) 89 (55.6%) 68 (66.7%) 91 (63.6%) 61 (55.5%) race white (%) 87 (52.4%) 15 (48.4%) 35 (54.7%) 48 (60.8%) 77 (48.1%) 57 (55.9%) 79 (55.2%) 54 (49.1%) asian (%) 60 (36.1%) 16 (51.6%) 26 (40.6%) 23 (29.1%) 50 (31.3%) 37 (36.3%) 49 (34.3%) 45 (40.9%) black or african american (%) 14 (8.4%) 0 (0%) 1 (1.6%) 4 (5.1%) 23 (14.4%) 4 (3.9%) 11 (7.7%) 8 (7.3%) other (%) 5 (3.0%) 0 (0%) 2 (3.1%) 3 (3.8%) 10 (6.3%) 4 (3.9%) 4 (2.8%) 2 (1.8%) duration current aa episode (years) mean (sd) 4.87 (6.24) 2.48 (2.51) 2.93 (4.30) 4.08 (4.74) 4.63 (3.91) 3.33 (3.21) 2.97 (2.72) 3.54 (3.13) duration current aa episode <4 years (%) 98 (59.0%) 26 (83.9%) 54 (84.4%) 52 (65.8%) 76 (47.5%) 72 (70.6%) 107 (74.8%) 74 (67.3%) >=4 years (%) 68 (41.0%) 5 (16.1%) 10 (15.6%) 27 (34.2%) 84 (52.5%) 30 (29.4%) 36 (25.2%) 36 (32.7%) duration since aa onset (years) mean (sd) 14.1 (11.0) 7.99 (8.63) 11.3 (10.2) 12.1 (10.8) 14.8 (11.8) 10.2 (10.5) 9.60 (9.79) 11.9 (11.3) aa severity categories severe (salt score 50-94) (%) 49 (29.5%) 28 (90.3%) 31 (48.4%) 39 (49.4%) 44 (27.5%) 76 (74.5%) 79 (55.2%) 49 (44.5%) very severe (salt score 95-100) (%) 117 (70.5%) 3 (9.7%) 33 (51.6%) 40 (50.6%) 116 (72.5%) 26 (25.5%) 64 (44.8%) 61 (55.5%) salt score mean (sd) 91.7 (14.7) 72.2 (15.1) 81.9 (20.5) 83.9 (19.1) 91.4 (15.7) 76.9 (18.3) 83.2 (18.4) 86.0 (17.7) classified as universalis yes (%) 77 (46.4%) 13 (41.9%) 34 (53.1%) 29 (36.7%) 86 (53.8%) 31 (30.4%) 64 (44.8%) 57 (51.8%) proportion of 4mg-treated patients who achieved a salt score ≤20 response over 52 weeks in different response pattern subgroups adalimumab efficacy in hidradenitis suppurativa patients is sustained at least three years with weekly dosing: results from a phase 3 open-label extension study (pioneer) christos c zouboulis,1 martin m okun,2 robert gniadecki,3 peter a foley,4 charles lynde,5 jamie weisman,6 piyalal karunaratne,7 david a williams7 1departments of dermatology, venereology, allergology and immunology, dessau medical center, bradenburg medical school theodor fontane, dessau, germany; 2fort healthcare, fort atkinson, wi, usa ; 3bispebjerg hospital, copenhagen, denmark; 4department of medicine (dermatology), the university of melbourne, st vincent’s hospital melbourne, skin & cancer foundation inc, and probity medical research, carlton, australia; 5the lynde centre for dermatology and probity medical research, markham, on, canada; 6advanced medical research, pc, atlanta, ga, usa; 7abbvie inc, north chicago, il, usa introduction 1. kimball, nejm. • data (locf) for the hs patient populations receiving weekly ada spanning the pioneer i and ii studies and the ole, confirm that weekly ada treatment maintained long-term response, demonstrated by: – 52.3% of the adaew population and 57.1% of the prr population achieved hiscr at week 168 – pain decreased starting at week 2, and was generally maintained to week 168 for both populations – clinically meaningful improvement in dlqi at week 72 of 6.5 • the safety profile of long-term weekly ada therapy in this analysis was consistent with the known ada safety profile and no new safety risks were identified. disclosures c zouboulis has received honoraria from abbvie for participation on ad boards, as a consultant, investigator, and speaker; his department received grants from abbvie and novartis for his participation as an investigator. m okun received compensation from abbvie for consultation services and is a former abbvie employee. he has served as a consultant for gilead sciences and crescendo biosciences. r gniadecki has received honoraria from abbvie, janssen, novartis, and amgen for participation on advisory boards, as a investigator, and speaker; his department received grants from abbvie, janssen and novartis for his participation as an investigator. p foley has served as a consultant, investigator, speaker and/or advisor for and/or received travel grants from galderma, leo/ peplin, ascent, clinuvel, janssen-cilag, eli lilly, australian ultraviolet services, roche, csl, 3m/inova/valeant, gsk/stiefel, abbott/abbvie, biogen idec, merck serono, schering-plough/msd, wyeth/pfizer, amgen, novartis, celgene, aspen, boehringer ingelheim and bms. c lynde has received honoraria as a principal investigator, speaker, and consultant for abbvie, amgen, boehringer ingelheim, celgene, eli lilly, janssen, leo pharma, merck, novartis, and regeneron. j weisman received research grants for investigator services from abbvie, allergan, amgen, astra zeneca, boehringer ingelheim, braintree, celgene, eli lilly, glaxo smith klein, janssen, leo pharma, merck, novartis, pfizer, regeneron, steifel, tigercat; and received honoraria for service on advisory boards and speaker’s bureaus from abbvie, amgen, celgene, eli lilly, and janssen. p karunaratne, d williams receive a salary as abbvie employees, and may also receive stocks and/or stock options. abbvie inc. funded this study and participated in the study design; study research; collection, analysis and interpretation of data; and writing, reviewing and approving of this publication. all authors had access to the data, and participated in the development, review, and approval, and in the decision to submit this publication. the authors would like to acknowledge yihua gu for statistical support, and jody bennett for medical writing support in the production of this publication; both are employed by abbvie. methods results conclusions references • hidradenitis suppurativa (hs) is a painful, chronic skin disease, characterized by recurrent inflamed nodules and abscesses, fistula formation, purulent drainage, and subsequent scarring. • the pioneer i and ii phase 3 trials1 evaluated treatment of patients with moderate-to-severe hs, with originator adalimumab (abbvie) dosed every week. adalimumab (ada) is approved for a wide range of inflammatory diseases, including moderate-to-severe hs. • the pioneer trials were followed by a phase 3, open-label extension (ole) trial (nct01635764) designed to determine the long-term safety and efficacy of ada in patients with moderate to severe hs. • this analysis reports long-term results for patients who received weekly ada weekly throughout pioneer i and ii, and continuing through the ole to week 168. • patients in this analysis entered the ole if they completed periods a and b or lost response during period b of pioneer i or ii. • in pioneer i or ii, patients were randomized to 40 mg weekly ada at the start of the 12-week period a, and upon completion of period a, were re-randomized to 40 mg weekly ada at the start of the 24-week period b (figure 1). throughout the ole, all patients received 40 mg weekly ada. figure 1. study design for pioneer i and ii, and open-label extension a. stratified by bl hurley stage ii vs iii (pioneer i & ii) & bl concomitant antibiotic use (pioneer ii). b. 160 mg week 0; 80 mg week 2; 40 mg from week 4. c. re-randomization at entry to period b, stratified by week 12 hiscr status & bl hurley stage ii vs iii. d. 160 mg week 12; 80 mg week 14; 40 mg from week 16. ada=adalimumab; ew=every week dosing; pbo=placebo; bl=baseline; pro=patient-reported outcomes. statistical analysis • adaew population: patients who received continuous 40 mg weekly ada in periods a and b of pioneer i or ii and in the ole. • prr population: patients in the adaew population who either achieved hiscr at week 12, or did not achieve hiscr but achieved at least a partial response to treatment at week 12 – hiscr (hidradenitis suppurativa clinical response) was defined as ≥50% reduction in an count with no increase in abscess count and no increase in draining fistula count relative to baseline – partial response was defined as ≥25% reduction in total abscess and inflammatory nodule (an) count relative to baseline, at the end of period a in pioneer i or ii. • all patients who were treated with ada weekly in periods a and b of pioneer i and ii, and entered the ole, were included in the analysis. • missing values were handled by non-responder imputation (nri) in periods a and b of pioneer i and ii, and last-observation-carried-forward (locf) and observed case were used for both continuous and categorical variables. • results are reported as “study weeks,” which consist of pioneer + ole weeks, shown consecutively. a. weeks include pioneer i or ii + the ole, listed consecutively. • the an count, draining fistula count, and total fistula count (sum of draining fistulas and non-draining fistulas) (locf) decreased from baseline in both populations, and remained generally stable to study-week 168 (figure 3a-c). figure 3. improvement in lesion count a. an count b. draining fistulas c. total fistulas a. weeks include pioneer i or ii + the ole, listed consecutively. mean improvement is relative to baseline. • improvement from baseline in pain (locf), indicated by mean percent decrease in nrs scores, remained generally stable in both populations to week 168 (figure 4). figure 4. improvement in skin pain a. weeks include pioneer i or ii + the ole, listed consecutively. mean changes are relative to baseline. change in numeric rating scale (nrs) at worst at each visit among patients with baseline nrs ≥3. • in both populations, there was a clinically meaningful decrease in dlqi (locf) from baseline through week 72. (figure 5a). the percentage of patients who achieved dlqi 0 or 1 increased from baseline to week 48 and was generally maintained to week 72 (figure 5b). figure 5. improvement in dermatology specific quality of life a. mean improvement from baseline b. achievement of dlqi 0 or 1 a. weeks include pioneer i or ii + the ole, listed consecutively. mean changes are relative to baseline. dlqi 0 or 1=dermatology quality of life index, no effect of skin disease on quality of life. safety • there were no adverse events of opportunistic infection excluding oral candidiasis, no events of tuberculosis, lymphoma, non-melanoma skin cancer, malignancy, or demyelinating disorder, and there were no deaths. table 2. treatment-emergent adverse events adverse events, n (%) adaew population n=88 prr population n=63 any event 76 (86.4) 55 (87.3) leading to study drug discontinuation 13 (14.8) 10 (15.9) serious 12 (13.6) 9 (14.3) infections 63 (71.6) 45 (71.4) serious infections 3 (3.4) a 2 (3.2) b active or latent tuberculosis 2 (3.2) 2 (3.2) a. included pneumonia (n=2) and cellulitis of right leg (n=1). b. included pneumonia (n=1) and cellulitis of right leg (n=1). • for patients who were randomized to weekly ada in period a of the 2 trials, the primary endpoint outcome (pooled data), was achievement of hiscr at week 12 by 50.6% of patients (160/316), which was significantly higher than for patients randomized to placebo (26.8%; 85/317); p<0.001. • in this analysis of results across pioneer i and ii (pooled data) into the ole, 88 patients were in the adaew population and 63 were in the prr population. • the hiscr rate (locf) increased from baseline to week 48 in both populations and was maintained to week 108 (figure 2). figure 2. achievement of hiscr fc17posterabbviezouboulisadalimumabefficacyinhidradenitis.pdf introduction/objective ■ guselkumab is a fully human monoclonal antibody that binds and blocks interleukin-23 function ■ voyage 1 is an ongoing, phase 3, double-blinded, placeboand active comparator-controlled study that evaluates the efficacy and safety of guselkumab in patients with moderate-to-severe plaque psoriasis1,2 ■ here, efficacy results following up to 4 years of continuous guselkumab treatment are presented methods ■ in voyage 1 (n=837), patients were randomized as follows (figure 1): — guselkumab 100 mg administered by subcutaneous (sc) injection at weeks 0, 4, and 12, then every 8 weeks (q8wk) — placebo at weeks 0, 4, and 12, followed by guselkumab 100 mg sc at weeks 16 and 20, then q8wk — adalimumab 80 mg sc at week 0, 40 mg at week 1, then 40 mg q2wk through week 47 — starting at week 52, all patients received open-label guselkumab treatment through week 204 ■ efficacy assessments included proportions of patients achieving psoriasis area and severity index (pasi) 90, pasi 100, investigator’s global assessment (iga) score of cleared (0) or minimal (1), and iga score of 0 ■ patient-reported outcomes included proportions of patients achieving a dermatology life quality index (dlqi) score of 0 or 1 (no effect on a patient’s health-related quality of life) and psoriasis symptoms and signs diary (pssd) summary scores of 0 (no symptoms or signs of psoriasis) ■ efficacy was analyzed using prespecified treatment failure rules (tfr), nonresponder imputation (nri), and as observed (obs) methodology — for tfr, patients who discontinued due to lack of efficacy, worsening of psoriasis, or use of a protocol-prohibited psoriasis treatment were considered nonresponders — for nri, patients with missing efficacy data (regardless of the reason) after application of tfr were counted as nonresponders — for obs, only patient data from each visit were used; missing data were not imputed ■ data for patients randomized to guselkumab and for those originally randomized to placebo who then crossed over to guselkumab at week 16 were combined (guselkumab group) and presented in this analysis figure 1. voyage 1 study design through 204 weeks placebocontrolled guselkumab 100 mg at weeks 0 and 4, then q8w guselkumab 100 mg at week 52, then q8wadalimumab 80 mg at week 0, 40 mg at week 1, then q2w guselkumab 100 mg at weeks 16 and 20, then q8w placebo placebocrossover active-comparator period open-label guselkumab (n=329) placebo (n=174) adalimumab (n=334) weeks 0 4 16 pe se = randomization q2w= every 2 weeks q8w= every 8 weeks pe = primary endpoint se = secondary endpoint 24 se 204 4 year dbl r r 48 se 52 results ■ pasi 90 responses were well-maintained with up to 4 years of continuous guselkumab treatment (figure 2) ■ at week 204, pasi 90 response rates were 82.2%, 68.4%, and 84.3%, respectively, based on tfr, nri, and obs analyses (figure 2) ■ similarly, pasi 100, iga score of 0 or 1, and iga score of 0 responses were stably maintained from week 52 through week 204 (figures 3-5) figure 2. proportion of patients who achieved pasi 90 response from week 52 through week 204 (tfr, nri, obs)* 0 20 40 60 80 100 p e rc e n ta g e o f p a ti e n ts 82.1 75.5 82.279.7 74.5 68.4 80.6 83.3 84.3 82.9 72.5 84.0 52 60 68 76 84 92 100 108 116 124 132 140 148 156 164 172 180 188 196 204 tfr: nri: 448 494 442n=463 n=494 n=468 411 494 401 432 494 425obs: weeks guselkumab (tfr) guselkumab (nri) guselkumab (obs) *includes patients randomized to guselkumab at baseline and to placebo who crossed over and were treated with guselkumab at week 16. figure 3. proportion of patients who achieved pasi 100 response from week 52 through week 204 (tfr, nri, obs)* 0 20 40 60 80 100 p e rc e n ta g e o f p a ti e n ts weeks tfr: nri: 448 494 442n=463 n=494 n=468 411 494 401 432 494 425obs: 52 60 68 76 84 92 100 108 116 124 132 140 148 156 164 172 180 188 196 204 guselkumab (tfr) guselkumab (nri) guselkumab (obs) 46.4 49.7 44.546.6 51.8 51.8 49.1 51.1 50.9 46.4 57.1 55.7 *includes patients randomized to guselkumab at baseline and to placebo who crossed over and were treated with guselkumab at week 16. figure 4. proportion of patients who achieved iga score of 0 or 1 from week 52 through week 204 (tfr, nri, obs)* 0 20 40 60 80 100 p e rc e n ta g e o f p a ti e n ts guselkumab (tfr) guselkumab (nri) guselkumab (obs) 52 60 68 76 84 92 100 108 116 124 132 140 148 156 164 172 180 188 196 204 tfr: nri: 448 494 442n=463 n=494 n=468 410 494 400 430 494 423obs: weeks 84.4 83.5 83.3 82.1 75.5 71.5 85.5 84.6 80.2 83.8 81.7 67.8 *includes patients randomized to guselkumab at baseline and to placebo who crossed over and were treated with guselkumab at week 16. figure 5. proportion of patients who achieved iga score of 0 from week 52 through week 204 (tfr, nri, obs)* 0 20 40 60 80 100 p e rc e n ta g e o f p a ti e n ts tfr: nri: 448 494 442n=463 n=494 n=468 410 494 400 430 494 423obs: 52 60 68 76 84 92 100 108 116 124 132 140 148 156 164 172 180 188 196 204 weeks guselkumab (tfr) guselkumab (nri) guselkumab (obs) 56.3 46.4 55.6 54.1 50.4 53.3 54.2 53.6 50.8 47.4 58.5 57.1 *includes patients randomized to guselkumab at baseline and to placebo who crossed over and were treated with guselkumab at week 16. ■ proportions of patients with pssd summary scores of 0 and dlqi score of 0 or 1 were sustained from week 76 through week 204 (figures 6-8) figure 6. pssd symptom score=0 from weeks 76-204 (tfr)* 39.2 40.2 42.8 39.8 45.4 42.543.6 41.8 45.9 44.0 49.1 43.0 0 20 40 60 80 100 week 76 week 156 week 172 week 204week 100 week 124 p er ce nt ag e of p at ie nt s 347 343 339 327 315 313227 225 222 218 212 207n = guselkumab adalimumab→guselkumab *patients with baseline pssd symptom score >0. weeks 76-204: guselkumab – includes patients randomized to guselkumab at baseline and to placebo who crossed over and were treated with guselkumab at week 16; adalimumab→guselkumab – includes patients randomized to adalimumab at baseline and crossed over and were treated with guselkumab at or after week 52. figure 7. pssd sign score=0 from weeks 76-204 (tfr)* 29.4 32.9 33.0 28.7 34.9 33.231.1 29.2 35.9 31.5 39.4 29.3 0 20 40 60 80 100 week 76 week 156 week 172 week 204week 100 week 124 p er ce nt ag e of p at ie nt s 347 343 339 327 315 313228 226 223 219 213 208n = guselkumab adalimumab→guselkumab *patients with baseline pssd sign score >0. weeks 76-204: guselkumab – includes patients randomized to guselkumab at baseline and to placebo who crossed over and were treated with guselkumab at week 16; adalimumab→guselkumab – includes patients randomized to adalimumab at baseline and crossed over and were treated with guselkumab at or after week 52. figure 8. dlqi score of 0 or 1 from weeks 76-204 (tfr)* 75.7 75.2 74.5 73.3 76.2 75.375.0 74.0 76.1 74.5 78.0 72.5 0 20 40 60 80 100 week 76 week 156 week 172 week 204week 100 week 124 p er ce nt ag e of p at ie nt s 445 436 431 420 404 396264 262 259 255 250 244n = guselkumab adalimumab→guselkumab *patients with baseline dlqi score >1. weeks 76-204: guselkumab – includes patients randomized to guselkumab at baseline and to placebo who crossed over and were treated with guselkumab at week 16; adalimumab→guselkumab – includes patients randomized to adalimumab at baseline and crossed over and were treated with guselkumab at or after week 52. table 1. adverse events (aes) through weeks 48, 100, 156, and 204 among patients randomized to guselkumab and placebo crossover patients guselkumab weeks 0-48 weeks 0-100 weeks 0-156 weeks 0-204 treated patients, n 494 494 494 494 average duration of follow-up, weeks 41.6 89.4 139.2 179.0 ≥1 ae, n (%) 350 (70.9%) 395 (80.0%) 426 (86.2%) 437 (88.5%) discontinued due to ≥1 ae, n (%) 10 (2.0%) 14 (2.8%) 21 (4.3%) 29 (5.9%) ≥1 sae, n (%) 21 (4.3%) 45 (9.1%) 66 (13.4%) 82 (16.6%) infections, n (%) 248 (50.2%) 302 (61.1%) 335 (67.8%) 347 (70.2%) requiring antibiotics 79 (16.0%) 124 (25.1%) 154 (31.2%) 169 (34.2%) serious infections 3 (0.6%) 6 (1.2%) 11 (2.2%) 15 (3.0%) malignancies other than nmsc, n (%) 2 (0.4%) 6 (1.2%) 9 (1.8%) 13 (2.6%) nmsc, n (%) 2 (0.4%) 2 (0.4%) 3 (0.6%) 8 (1.6%) mace, n (%) 1 (0.2%) 1 (0.2%) 2 (0.4%) 3 (0.6%) deaths, n (%) 0 2 (0.4%) 4 (0.8%) 4 (0.8%) mace=major adverse cardiovascular event; nmsc=nonmelanoma skin cancer; sae=serious adverse event other safety events ■ no opportunistic infections were reported ■ no anaphylactic or serum sickness-like reactions were reported ■ common terminology criteria for adverse events (ctcae) grade ≥2 in blood hematology and chemistry laboratory values were uncommon conclusions ■ high efficacy response rates were maintained with up to 4 years of continuous guselkumab treatment in voyage 1, regardless of the analysis method (tfr, nri, and obs) ■ no new safety signals were identified references 1. blauvelt a., et al. j am acad dermatol. 2017;76(3):405-417. 2. griffiths c.e.m., et al. j drugs dermatol. 2018;17(8):826-832. this poster was supported by janssen research & development, llc maintenance of response with up to 4 years of continuous guselkumab treatment: results from the voyage 1 phase 3 trial c.e.m. griffiths,1 k.a. papp,2 m. song,3 m. miller,3 y. you,3 y-k. shen,3 c. han,3 a. blauvelt4 1dermatology centre, university of manchester, manchester, uk; 2k. papp clinical research and probity research inc., waterloo, ontario, canada; 3janssen research & development, llc, spring house, pa, usa; 4oregon medical research center, portland, or, usa 101102042_cobi_pop_pk_l1a presented at the winter clinical dermatology conference; january 13-18, 2023; kohala coast, hawaii copies of this poster obtained through this qr code, are for your personal use only and may not be reproduced without permission from the authors. copyright © 2023. all rights reserved. background • dupilumab, an anti–interleukin 4 receptor alpha monoclonal antibody, is approved for the treatment of patients with atopic dermatitis (ad) who are candidates for systemic therapy1 • patients with moderate-to-severe ad who do not respond to dupilumab have limited treatment options • abrocitinib is a janus kinase 1 (jak1) inhibitor that is under investigation for the treatment of moderate-to-severe ad2,3 objective • to assess the proportion of dupilumab nonresponder patients from jade compare who experienced clinically meaningful improvement in signs and symptoms of ad after switching to abrocitinib in jade extend methods • phase 3 jade compare included adults with moderate-to-severe ad and inadequate response to topical medication or a need for systemic therapy to control ad • this post hoc analysis focused on patients with moderate-to-severe ad who received dupilumab and concomitant topical therapy for 16 weeks in jade compare followed by entry into jade extend (figure 1) • upon entering jade extend, patients were randomized to either abrocitinib 200 mg or 100 mg once daily • in jade extend, medicated topical therapy was permitted but not required • patients who did not achieve an investigator’s global assessment (iga) of 0 or 1 with ≥2-point improvement, ≥75% or ≥90% improvement in eczema area and severity index (easi), 4-point improvement on the peak pruritus numerical rating scale (pp-nrs), or pp-nrs score of 0 or 1 at week 16 with dupilumab were reassessed at week 32 with abrocitinib 200 mg or 100 mg • safety was assessed by monitoring treatment-emergent adverse events (teaes) figure 1. study design medicated topical therapy (lowand/or medium-potency corticosteroids, calcineurin inhibitors, and phosphodiesterase 4 inhibitor) required for active lesions medicated topical therapy was permitted but not required dupilumab 300 mg sc q2w + oral placebo qd (n=242) oral placebo abrocitinib 100 mg qd (n=130) abrocitinib 200 mg qd (n=73) treatment period: 16 weeks (last dupilumab dose at week 14) 4-week washout current analysis week 32 week 20 week 16 week 0eligibility criteria • adult patients (≥18 years) with ad ≥1 year • moderate-to-severe ad (iga ≥3; easi ≥16; %bsa ≥10; pp-nrs ≥4) • inadequate response to topical medication, or need for systemic therapy to control ad jade compare jade compare jade extend ad, atopic dermatitis; %bsa, percentage of affected body surface area; easi, eczema area and severity index; iga, investigator’s global assessment; pp-nrs, peak pruritus numerical rating scale; q2w, every 2 weeks; qd, once daily; sc, subcutaneous. the pp-nrs is used with permission of regeneron pharmaceuticals, inc., and sanofi. results patients • disease characteristics were well balanced across treatment arms at entry to jade extend (table 1) • most patients had moderate ad per iga: 64.4% of patients in the 200-mg arm and 66.9% in the 100-mg arm abrocitinib in the treatment of moderate-to-severe atopic dermatitis refractory to dupilumab treatment: an analysis of jade-extend, a phase 3 long-term extension study vivian shi,1 tina bhutani,2 mette deleuran,3 luz fonacier,4 stephen shumack,5 fan zhang,6 michael c. cameron,7 gary chan,6 hernan valdez,7 natalie yin7 1university of arkansas for medical sciences, little rock, ar, usa; 2ucsf, san francisco, ca, usa; 3aarhus university hospital, aarhus, denmark; 4nyu langone hospital–long island, new york, ny, usa; 5university of sydney, royal north shore hospital, sydney, nsw, australia; 6pfizer inc., groton, ct, usa; 7pfizer inc., new york, ny, usa table 1. baseline characteristics (safety population)a abrocitinib 100 mg qd n=130 abrocitinib 200 mg qd n=73 duration of ad, mean (sd), y 24.2 (15.0) 23.6 (15.6) iga, n (%) moderate (3) severe (4) 87 (66.9) 43 (33.1) 47 (64.4) 26 (35.6) %bsa, mean (sd) 45.4 (21.2) 47.9 (22.9) easi, mean (sd) 29.6 (11.2) 31.2 (12.4) pp-nrs, mean (sd) 7.4 (1.7) 7.2 (1.6) ad, atopic dermatitis; %bsa, percentage of affected body surface area; easi, eczema area and severity index; iga, investigator’s global assessment; pp-nrs, peak pruritus numerical rating scale; qd, once daily; sd, standard deviation. asafety population represents all patients who received prior dupilumab in jade compare and were randomly assigned to receive abrocitinib in jade extend. efficacy • a substantial portion of dupilumab nonresponders achieved clinically meaningful efficacy responses after switching to abrocitinib (figure 2) • among dupilumab iga 0/1 nonresponders (based on failing to achieve an iga of clear [0] or almost clear [1] and ≥2-grade improvement from baseline in jade compare), 47.2% of the abrocitinib 200-mg group and 35.2% of the abrocitinib 100-mg group achieved iga 0/1 at week 12 of jade extend • among dupilumab easi-75 nonresponders (based on failing to achieve at least a 75% improvement from baseline in easi in jade compare), 80.0% of the abrocitinib 200-mg group and 67.7% of the abrocitinib 100-mg group achieved easi-75 at week 12 of jade extend • among dupilumab easi-90 nonresponders (based on failing to achieve at least a 90% improvement from baseline in easi in jade compare), 59.5% of the abrocitinib 200-mg group and 39.7% of the abrocitinib 100-mg group achieved easi-90 at week 12 of jade extend • among dupilumab pp-nrs4 nonresponders (based on failing to achieve at least a 4-point improvement from baseline in pp-nrs in jade compare), 77.3% of the abrocitinib 200-mg group and 37.8% of the abrocitinib 100-mg group achieved pp-nrs4 at week 12 of jade extend (representing a clinically meaningful improvement in itch) • among dupilumab pp-nrs 0/1 nonresponders (based on failing to achieve a pp-nrs score of 0 [representing no itch] or 1 [representing minimal itch] in jade compare), 42.9% of the abrocitinib 200-mg group and 25.8% of the abrocitinib 100-mg group achieved pp-nrs 0/1 at week 12 of jade extend figure 2. abrocitinib efficacy at week 12 among dupilumab nonresponders 60 70 80 90 100 0 10 20 30 40 50 p ro po rt io n of p at ie nt s, % na iga 0/1 71 36 35.2 47.2 easi-75 31 20 67.7 80.0 easi-90 68 37 39.7 59.5 pp-nrs4 45 22 37.8 77.3 pp-nrs 0/1 89 42 25.8 42.9 abrocitinib 100 mg qd abrocitinib 200 mg qd easi-75, ≥75% improvement from baseline in eczema area and severity index; easi-90, ≥90% improvement from baseline in eczema area and severity index; iga 0/1, investigator’s global assessment of clear (0) or almost clear (1) and ≥2-grade improvement from baseline; pp-nrs4, ≥4-point improvement from baseline in peak pruritus numerical rating scale score; pp-nrs 0/1, peak pruritus numerical rating scale score of 0 (no itch) or 1 (minimal itch); qd, once daily. anumber of dupilumab nonresponders according to each efficacy endpoint at week 16 of jade compare. safety • teaes were reported in 50.7% of patients in the abrocitinib 200-mg group and in 41.5% of patients in the abrocitinib 100-mg group (table 2) • the incidence of adverse events (aes) that were serious, severe, or led to study discontinuation was <3% • the most common ae in both abrocitinib treatment arms was nasopharyngitis, occurring in 11.0% of patients in the 200-mg group and 6.9% of patients in the 100-mg group table 2. safety abrocitinib 100 mg qd n=130 abrocitinib 200 mg qd n=73 patients who had ≥1 teae, n (%) serious severe leading to study discontinuation 54 (41.5) 3 (2.3) 3 (2.3) 1 (0.8) 37 (50.7) 1 (1.4) 2 (2.7) 1 (1.4) teaes reported for ≥4 patients in any group, n (%) nasopharyngitis nausea acne headache upper respiratory tract infection urinary tract infection 9 (6.9) 0 3 (2.3) 1 (0.8) 6 (4.6) 4 (3.1) 8 (11.0) 6 (8.2) 5 (6.8) 5 (6.8) 2 (2.7) 1 (1.4) qd, once daily; teae, treatment-emergent adverse event. conclusions • in a substantial proportion of dupilumab nonresponders, clinically meaningful improvement in signs (iga, easi-75, easi-90) and symptoms (pp-nrs4, pp-nrs 0/1) of moderate-to-severe ad was achieved after switching to abrocitinib • the safety profile of abrocitinib in jade extend was consistent with previous studies; no new safety signals were observed at 12 weeks • the efficacy and safety profile of oral abrocitinib 200 mg or 100 mg qd in this analysis supports the role of abrocitinib as treatment for patients with moderate-to-severe ad, regardless of prior experience with dupilumab references 1. dupixent (dupilumab) injection, for subcutaneous use (prescribing information). bridgewater, nj: sanofi and regeneron pharmaceuticals; may 2020. 2. simpson el et al. lancet. 2020;396:255-266. 3. silverberg ji et al. jama dermatol. 2020;156:863-873. acknowledgments editorial/medical writing support under the guidance of authors was provided by renee gordon, phd, and richard w. davis iv, phd, at apothecom (san francisco, ca, usa), and was funded by pfizer inc., new york, ny, usa, in accordance with good publication practice (gpp 2022) guidelines (ann intern med. 2022; 10.7326/m22-1460). these studies were sponsored by pfizer, inc. previously presented at the american academy of dermatology vmx 2021 congress [virtual]; april 23-25, 2021. disclosures vs is a stock shareholder of learn health and has served as an advisory board member or investigator and/or received research funding from pfizer inc., sanofi-genzyme, regeneron, abbvie, eli lilly, novartis, sun pharma, leo pharma, menlo therapeutics, dermira, burt’s bees, galderma, kiniksa pharmaceuticals, ucb, altus lab, myor, polyfin, gpskin, and skin actives scientific. tb is an investigator for pfizer inc., abbvie, galderma, mindera, and regeneron. she has served as a consultant and/or advisory board member for pfizer inc., abbvie, arcutis, boehringer ingelheim, bristol myers squibb, janssen, leo pharma, lilly, novartis, sun, and ucb. md has been a consultant, advisory board member, and/or speaker for pfizer inc., abbvie, eli lilly, leo pharma, regeneron, sanofi-genzyme, and pierre fabre. lf has been a consultant and advisory board member for pfizer inc., regeneron, abbvie, and lilly, and has received research and educational grants (made to nyu langone hospital–long island) from pfizer inc., regeneron, astrazeneca, and shire. ss has been an investigator, advisory board member, and/or speaker for pfizer inc., abbvie, lilly, leo pharma, sanofi, and novartis. mcc is a former employee of pfizer inc. and may hold stock options. fz, gc, hv, and ny are employees and shareholders of pfizer inc. skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 563 brief articles recurrence of primary cutaneous anaplastic large cell lymphoma at a new location after wide surgical excision payvand kamrani, do1, madeline schaeffer, do2, david altman, md3 1reading hospital/tower health; reading, pa 2st. joseph mercy health system; ann arbor, mi 3midwest center for dermatology; warren, mi primary cutaneous anaplastic large cell lymphoma (pcalcl) and lymphomatoid papulosis (lyp) represent a disease spectrum of cutaneous cd30-positive lymphoproliferative disorders. together, they are the second most common type of cutaneous t-cell lymphoma after mycosis fungoides. histology of pcalcl reveals a dense dermal infiltrate of large t-cells with at least 75% of the tumor cells expressing the cd-30 antigen.1 prognosis is favorable with a 5-year survival rate ranging from 85100%.2,3 clinical presentation is most often a solitary tumor; however multifocal disease with more than one lesion may occur. we report a case of a 54-year-old male with pcalcl manifesting as a tumor on the chest. despite wide local excision with a depth down to the pectoralis major muscle, the disease recurred in the same area two months later. a healthy 54-year-old man presented with a several months history of an enlarging pinkred shiny nodule on his mid-chest with a few clustered satellite papules (figure 1). he denied fever, fatigue, night sweats, weight loss, or a history of malignancy. initial punch biopsies supported a diagnosis of reactive lymphoid hyperplasia. the tumor continued to enlarge and coalesce, reaching a size of 4.3 by 4.2 cm despite treatment with systemic, topical, and intralesional corticosteroids. given the concern for a malignant process, the patient underwent wide local excision down to the pectoralis major muscle. the timing from the initial biopsy to excision was roughly 5 months. histology of the excised specimen demonstrated a dense atypical lymphoid infiltrate in the dermis and subcutaneous tissue with a predominant population of large, cd3 and cd30-positive t-cells displaying nuclear atypia and abundant cytoplasm (figure 3). p63 highlighted approximately 40% of the atypical t lymphocytes. tia, granzyme, alk and cd56 were negative. a second population of small, cd20-positive b-cells formed irregular lymphoid follicles, but were determined to be reactive due to a lack of clonality. examined inked margins were negative for malignancy. the patient was sent for oncologic evaluation and a pet scan was negative for any metabolically active neoplasm. patient denied a history of plaque or patch-like introduction case presentation skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 564 lesions preceding this nodule. this history and a thorough skin examination helped exclude a pre-existing mycosis fungoides. two months after excision, the patient presented with a new nodule on the right upper chest, several inches away from the initial site of occurrence (figure 4). shave biopsy confirmed recurrence of the tumor. the patient deferred radiation therapy and instead elected for serial skin examinations to monitor for growth. he was counseled on the probable need for radiation therapy in the future. figure 1. initial presentation of two enlarging and pruritic nodules on patient’s chest. figure 2. pre-excision photo with surgical ink figure 3. stain demonstrating an abundance of atypical lymphocytes (h&e, 40x) figure 4. recurrence of tumor two months after initial excision. the spectrum of cd30+ cutaneous lymphoproliferative disorders includes primary cutaneous anaplastic large cell lymphoma (pcalcl), lymphomatoid papulosis (lyp), and borderline cd30+ lesions.4 together, this group of disorders discussion skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 565 accounts for 25-30% of all cutaneous t-cell lymphomas (ctcl). pcalcl is a neoplasm composed of large atypical lymphocytes characterized by the expression of cellsurface receptor cd-30 antigen, a marker for t-cell activation, in more than 75% of tumor cells.2,5 pcalc is an uncommon malignancy with an incidence of 0.1 to 0.2 per 100,000.6 pcalcl is most commonly diagnosed in the sixth decade of life, with a slightly increased male to female ratio of 1.5 to 2:1. it is rare in children and adolescences.4 patients with pcalcl generally have an excellent prognosis with a 5-year survival rate ranging from 85-100%.2,3 no clinical or histological factors have been found to be predictive of a worse outcome.4 partial or complete spontaneous regression is possible, but unlikely. patients may present clinically with solitary or multifocal papules and/or nodules usually affecting the upper half of the body, which may enlarge and ulcerate over time.4 roughly 10% of cases may present with multifocal cutaneous disease in multiple anatomic regions at the time of diagnosis.7 before a diagnosis of palcl can be made, systemic anaplastic large cell lymphoma with secondary skin involvement must first be ruled out with imaging. primary cutaneous disease has a better prognosis when compared to systemic disease with secondary cutaneous involvement.7 cd30+ anaplastic large cell lymphomas can also develop secondarily from an aggressive transformation of mycosis fungoides, and is associated with rapidly fatal outcomes.9 the differential for pcalcl includes lyp, mycosis fungoides with large cell transformation, and reactive lymphoid hyperplasia. lyp typically presents with multiple widely distributed papulonodules that often spontaneously regress and recur. lyp type c in particular can be histologically nearly identical to pcalcl. monoclonal rearrangement of t-cell receptor can be detected in lyp demonstrating the lack of tcell clonality.10 therefore, differentiating between these two entities strongly relies on clinicopathologic correlation. regardless, the delineation between pcalcl and lyp remains a diagnostic challenge. histological examination of pcalcl reveals a dermal infiltrate comprised of a dense infiltrate of large blast-like cd30-positive tcells with pleomorphic nucleoli and abundant cytoplasm (figure 3). cd30, also known as ki-1, must be expressed by >75% of the tumor cells for diagnosis.7 the anaplastic lymphoma kinase (alk) gene, which demonstrates a nucleophosmin-alk gene translocation, is typically, but not always, absent in primary cutaneous alcl. in contrast, the alk gene is often present in systemic alcl.7 surgical excision is the most common initial therapy used for solitary palcl lesions, but studies have shown that relapses can occur in 43% of patients.6 time until recurrence ranges from 2-76 months, but most reported cases are unclear if relapse occurred at the original site or a new site.6 no predictive marker for the risk of cutaneous relapse has yet been identified. although our patient underwent extensive surgical excision (figure 2), recurrence still occurred. interestingly, the site of recurrence in our patient was not at the original tumor location, but approximately 8 cm away from the initial lesion. some reports recommend an initial four to eight-week period of observation as pcalcl may regress spontaneously.7 radiotherapy, either alone or in combination with surgical excision is also an acceptable treatment for solitary lesions.7 skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 566 combination chemotherapy (with various regimens reported) has been the initial firstline treatment for multifocal primary cutaneous disease. another possible approach to multifocal disease is anti-cd30 monoclonal antibody therapy. brentuximab vedotin, an anti-cd30 antibody drug conjugate has been reported to effectively treat extensive disease.6 in summary, pcalcl is the second most common form of cutaneous t-cell lymphoma. it can present as an enlarging solitary or multifocal nodule. systemic anaplastic large cell lymphoma with secondary skin involvement must be ruled out with imaging. treatment ranges from surgery, chemotherapy, and/or radiation depending on the number of lesions at presentation. however, despite treatment, relapse is common. abbreviations: lymphomatoid papulosis (lyp) primary cutaneous anaplastic large cell lymphoma (pcalcl) conflict of interest disclosures: none funding: none corresponding author: payvand kamrani, do reading hospital/tower health 420 s 5th ave reading, pa 19611 phone: 919-619-8369 fax: 609-357-9515 email: payvandkh@pcom.edu references: 1. baik bs, lee ws, ji sy, et al. treatment of primary cutaneous anaplastic large cell lymphoma. arch craniofac surg. 2019;20(3):207. 2. vergier b, beylot-barry m, pulford k, et al. statistical evaluation of diagnostic and prognostic features of cd30+ cutaneous lymphoproliferative disorders: a clinicopathologic study of 65 cases. am j surg pathol. 1998;22(10):1192-1202. 3. bekkenk mw, geelen fa, van voorst vader pc, et al. primary and secondary cutaneous cd30(+) lymphoproliferative disorders: a report from the dutch cutaneous lymphoma group on the longterm follow-up data of 219 patients and guidelines for diagnosis and treatment. blood. 2000;95(12):3653-3661. 4. liu hl, hoppe rt, kohler s, et al. cd30+ cutaneous lymphoproliferative disorders: the stanford experience in lymphomatoid papulosis and primary cutaneous anaplastic large cell lymphoma. j am acad dermatol. 2003;49(6):1049-58. 5. willemze r, jaffe es, burg g, et al. whoeortc classification for cutaneous lymphomas. blood. 2005;105:3768-85. 6. kempf w, pfaltz k, vermeer mh, et al. eortc, iscl, and usclc consensus recommendations for the treatment of primary cutaneous cd30positive lymphoproliferative disorders: lymphomatoid papulosis and primary cutaneous anaplastic large-cell lymphoma. blood. 2011:118(15):4024-4035. 7. shehan, jm, kalaaji an, markovic sn, et al. management of multifocal primary cutaneous cd30+ anaplastic large cell lymphoma. j am acad dermatol. 2004;51(1):103-110. 8. moodley n, nombona p, mosam a. primary cutaneous anaplastic large-cell lymphoma. dermatopathology, 2019;6(2):163169. 9. kang, s. k., chang, s. e., choi, j. h., sung, k. j., moon, k. c., & koh, j. k. (2002). coexistence of cd30‐positive anaplastic large cell lymphoma and mycosis fungoides. clinical and experimental dermatology, 27(3), 212-215. 10. werner kempf, m. d., katrin kerl, m. d., & christina mitteldorf, m. d. (2018, march). cutaneous cd30-positive t-cell lymphoproliferative disorders—clinical and histopathologic features, differential diagnosis, and treatment. in seminars in cutaneous medicine and surgery (vol. 37, pp. 24-29). conclusion presented at winter clinical derm 2023, january 13–18, 2023 (encore of previous presentation at the european association of dermato oncology [eado] congress 2022, april 21–23, stratigos aj et al.). reused with permission. phase 2 study of cemiplimab in patients with locally advanced basal cell carcinoma after hedgehog inhibitor therapy: long-term follow-up alexander j stratigos,1 aleksandar sekulic,2 ketty peris,3 oliver bechter,4 sorilla prey,5 martin kaatz,6 karl d lewis,7 nicole basset-seguin,8 anne lynn s chang,9 stéphane dalle,10 almudena fernandez orland,11 lisa licitra,12 caroline robert,13 claas ulrich,14 axel hauschild,15 michael r migden,16 reinhard dummer,17 suk-young yoo,18 ebony coates,18 emmanuel okoye,18 ioannis bassukas,19 carmen loquai,20 vincenzo de giorgi,21 zeynep eroglu,22 ralf gutzmer,23 jens ulrich,24 susana puig,25 frank seebach,18 israel lowy,18 matthew g fury18 1department of dermatology-venereology, andreas sygros hospital-national and kapodistrian university of athens, athens, greece; 2department of dermatology, arizona mayo clinic, scottsdale, az, usa; 3institute of dermatology, catholic university of the sacred heart and fondazione policlinico universitario a gemelli-irccs, rome, italy; 4department of general medical oncology, university hospitals, leuven, belgium; 5department of dermatology, bordeaux university hospital, bordeaux, france; 6department of dermatology, srh wald-klinikum gera gmbh, gera, germany; 7school of medicine, university of colorado, aurora, co, usa; 8department of dermatology, hôpital saint-louis, paris, france; 9department of dermatology, stanford university school of medicine, stanford, ca, usa; 10department of dermatology, centre hospitalier lyon-sud, lyon, france; 11department of dermatology, hospital universitario virgen macarena, seville, spain; 12medical oncology head and neck cancer department, fondazione irccs istituto nazionale dei tumori and university of milan, milan, italy; 13dermatology unit, gustave roussy cancer center and paris-saclay university, villejuif, france; 14skin cancer centre, charite-universitiitsmedizin berlin, berlin, germany; 15department of dermatology, university of kiel, kiel, germany; 16departments of dermatology and head and neck surgery, university of texas md anderson cancer center, houston, tx, usa; 17department of dermatology, university hospital zurich, zurich, switzerland; 18regeneron pharmaceuticals, inc, tarrytown, ny, usa; 19department of skin and venereal diseases, faculty of medicine, school of health sciences, university of ioannina, ioannina, greece; 20department of dermatology, university medical center mainz, mainz, germany; 21departments of dermatology and human pathology and oncology, university of florence, florence, italy; 22department of cutaneous oncology at moffitt cancer center, tampa, fl, usa; 23johannes westling medical center, ruhr university bochum, minden, germany; 24academic teaching hospital of the university otto von guericke magdeburg, magdeburg, germany; 25dermatology department, hospital clinic of barcelona, university of barcelona, barcelona, spain results patients • eighty-four patients with labcc were enrolled in this study, 66.7% were male, and median age was 70 years (range, 42−89). patient characteristics are provided in table 2. • the primary site of tumor location was head and neck (89.3%). • most common reasons for discontinuation of hhi therapy were progression of disease on hhis (71.4%), intolerance to prior hhis (38.1%), and no better than stable disease after 9 months on hhis (8.3%) (table 2). • median duration of follow-up was 15.9 months (range, 0.5−39.7). table 2. patient demographics and baseline characteristics characteristic labcc (n=84) age, median (range), years 70 (42–89) ≥65 to <75, n (%) 19 (22.6) ≥75, n (%) 34 (40.5) male, n (%) 56 (66.7) ecog performance status, n (%) 0 51 (60.7) 1 33 (39.3) patients with prior cancer-related radiotherapy, n (%) 42 (50.0) patients with prior hhi therapy, n (%) vismodegib 79 (94.0) sonidegib 14 (16.7) vismodegib + sonidegib 9 (10.7) reason for discontinuation of prior hhi, n (%)† progression of disease on hhi 60 (71.4) no better than stable disease after 9 months on hhi therapy 7 (8.3) intolerant to prior hhi therapy 32 (38.1) intolerant to vismodegib 32 (38.1) intolerant to sonidegib 4 (4.8) primary site of tumor, n (%) head and neck 75 (89.3) trunk 7 (8.3) extremity 2 (2.4) duration of exposure, median (range), weeks 47.2 (2.1–97.9) median number of doses of cemiplimab administered (range) 15.0 (1–31) †sum is >84 because some patients had more than one reason for discontinuation. ecog, eastern cooperative oncology group; hhi, hedgehog inhibitor; labcc, locally advanced basal cell carcinoma. table 1. inclusion and exclusion criteria inclusion criteria exclusion criteria • histologically confirmed diagnosis of invasive bcc • prior progression or intolerance to hhi therapy or no better than stable disease after 9 months on hhi therapy • at least one measurable baseline lesion • ecog performance status of 0 or 1 • ongoing or recent (within 5 years) autoimmune disease requiring systemic immunosuppression • prior anti–pd-1 or anti–pd-l1 therapy • concurrent malignancy other than bcc and/or history of malignancy other than bcc within 3 years of date of first planned dose of cemiplimab, except for tumors with negligible risk of metastasis or death bcc, basal cell carcinoma; ecog, eastern cooperative oncology group; hhi, hedgehog inhibitor; pd-1, programmed cell death-1; pd-l1, programmed cell death-ligand 1. conclusions • this long-term follow-up analysis further confirms the safety and efficacy of cemiplimab in patients with labcc after progression on or intolerance to hhi therapy. • there were no new safety signals compared with previous analyses of cemiplimab in labcc.12 • combined with the primary analysis12 in the labcc cohort and interim analysis13 from the mbcc cohort, these results confirm cemiplimab has substantial activity in advanced bcc tumors. references 1. puig s et al. clin transl oncol. 2015;17:497–503. 2. monroe m et al. otolaryngol clin north am. 2021;54:271–280. 3. sekulic a et al. n engl j med. 2012;366:2171–2179. 4. migden mr et al. lancet oncol. 2015;16:716–728. 5. basset-seguin n et al. lancet oncol. 2015;16:729–736. 6. burova e et al. mol cancer ther. 2017;16:861–870. 7. regeneron pharmaceuticals, inc. available at: https://www.accessdata.fda.gov/drugsatfda_docs/ label/2021/761097s007lbl.pdf. [accessed january 22, 2022]. 8. regeneron pharmaceuticals, inc. available at: https://www.prnewswire.com/news-releases/libtayo-cemiplimabapproved-by-the-european-commission-as-the-first-immunotherapy-indicated-for-patients-with-advanced-basalcell-carcinoma-301319988.html. [accessed january 22, 2022]. 9. health canada. available at: https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/ notice-compliance/conditions/libtayo-notice-compliance-conditions-218718.html. [accessed january 22, 2022]. 10. ministry of health israel. available at: https://israeldrugs.health.gov.il/#!/meddetails/164%2099%2036023%2000. [accessed january 22, 2022]. 11. brazilian health authority anvisa. available at: https://www.gov.br/anvisa/pt-br/assuntos/medicamentos/novosmedicamentos-e-indicacoes/libtayo-cemiplimabe-nova-indicacao. [accessed january 22, 2022]. 12. stratigos aj et al. lancet oncol. 2021;22:848–857. 13. lewis k et al. j immunother cancer. 2020;8:abstract 428. acknowledgments the authors thank the patients who participated in this study. medical writing and editorial support under the direction of the authors was provided by sameen yousaf, phd, of prime (knutsford, uk) and funded by regeneron pharmaceuticals, inc., and sanofi. disclosures alexander j stratigos reports advisory board or steering committee roles with janssen, regeneron pharmaceuticals, roche and sanofi; and research support from abbvie, bristol-myers squibb, genesis pharma and novartis. table 4. teaes† labcc (n=84) teaes, n (%) any grade grade ≥3 any 83 (98.8) 44 (52.4) serious 31 (36.9) 24 (28.6) led to discontinuation 15 (17.9) 9 (10.7) associated with an outcome of death‡ 4 (4.8) 4 (4.8) occurring in ≥10% of patients or grade ≥3 in ≥5% of patients§ fatigue 26 (31.0) 4 (4.8) diarrhea 20 (23.8) 0 pruritus 18 (21.4) 0 asthenia 17 (20.2) 1 (1.2) arthralgia 16 (19.0) 0 decreased appetite 13 (15.5) 1 (1.2) anemia 13 (15.5) 1 (1.2) nausea 12 (14.3) 1 (1.2) headache 12 (14.3) 1 (1.2) urinary tract infection 12 (14.3) 3 (3.6) dyspnea 10 (11.9) 0 cough 9 (10.7) 0 tumor hemorrhage 9 (10.7) 0 †aes were coded according to the preferred terms of the medical dictionary for regulatory activities, version 22.1. the severity of aes was graded according to the national cancer institute common terminology criteria for adverse events, version 4.03. ‡none of the deaths were considered treatment related. §aes are listed in descending order of frequency in any grade. ae, adverse event; labcc, locally advanced basal cell carcinoma; teae, treatment-emergent adverse event. synopsis • basal cell carcinoma (bcc) is the most common human malignancy worldwide.1 most patients with bcc are cured by surgical excision, but a small proportion develop advanced bcc, which includes locally advanced (labcc) and metastatic (mbcc) disease.1,2 • hedgehog signaling pathway inhibitors (hhis), such as vismodegib and sonidegib, are indicated for patients with mbcc or labcc who are not candidates for curative surgery or radiotherapy.3-5 most patients with advanced bcc, however, progress on or are intolerant to hhi therapy. • cemiplimab is a high-affinity, fully human, hinge-stabilized immunoglobulin g4 anti– programmed cell death-ligand 1 (pd-l1) antibody that potently blocks the interaction of programmed cell death-1 (pd-1) with its ligand.6 • cemiplimab (cemiplimab-rwlc in the us) is the first immunotherapy indicated for treatment of patients with mbcc and labcc after hhi treatment or for whom hhis are not appropriate.7-11 • in the primary analysis of the phase 2 study (nct03132636), cemiplimab demonstrated clinically meaningful activity and an acceptable safety profile in patients with labcc after hhi therapy or for whom hhis were not appropriate.12 here, we present the long-term follow-up data at approximately 40 months after the primary analysis of the first group in this study. objectives • the primary objective is to evaluate objective response rate (orr) by independent central review (icr). • key secondary endpoints include orr by investigator assessment, duration of response (dor), progression-free survival (pfs), overall survival (os), complete response rate, and safety and tolerability. methods • in this open-label, multicenter, single-arm, phase 2 trial, patients received cemiplimab 350 mg intravenously (iv) every 3 weeks (q3w) for up to 93 weeks or until disease progression, unacceptable toxicity, withdrawal of consent, or confirmed complete response (figure 1). the study design was previously reported in detail.12 figure 1. study design group 1 – adult patients with metastatic (nodal and distant) bcc cemiplimab 350 mg iv q3w for up to 93 weeks (or until disease progression, unacceptable toxicity, or withdrawal of consent) tumor assessments 1–5 q9w, 6–9 q12w tumor response assessment by icr (recist 1.1 for visceral lesions or modified who criteria for skin lesions)† group 2 – adult patients with labcc †or by composite response criteria for patient with both visceral and skin lesions, including icr review of digital medical photography, radiology and pathology reports from on-treatment biopsies (if any). bcc, basal cell carcinoma; icr, independent central review; iv, intravenous; labcc, locally advanced basal cell carcinoma; q3w, every 3 weeks; q9w, every 9 weeks; q12w, every 12 weeks; recist, response evaluation criteria in solid tumors; who, world health organization. • inclusion and exclusion criteria are provided in table 1. • tumor assessments were done at the end of each treatment cycle, every 9 weeks (q9w) for the first five cycles, and every 12 weeks (q12w) for the subsequent four cycles. • an updated analysis of the response was prespecified to be performed after all responding patients had been followed for a minimum of 12 months from onset of response. • the data cutoff date was may 20, 2021. 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 p a ti e n ts w it h r e s p o n s e month complete response partial response stable disease progressive disease unable to evaluate ongoing study figure 2. time to response and dor in responding patients per icr each horizontal bar represents one patient. all patients completed treatment. patients with confirmed complete response after a minimum of 48 weeks of treatment may elect to discontinue treatment and continue with all relevant study assessments. dor, duration of response; icr, independent central review; labcc, locally advanced basal cell carcinoma. table 3. tumor response per icr outcome labcc (n=84) duration of follow-up, median (range), months 15.9 (0.5–39.7) best overall response per icr orr, % (95% ci) 32.1 (22.4–43.2)† complete response, n (%) 6 (7.1) partial response, n (%) 21 (25.0) stable disease, n (%) 40 (47.6) non-complete response/non-progressive disease, n (%) 0 progressive disease, n (%) 9 (10.7) not evaluable, n (%)‡ 8 (9.5) observed dor at 6 months, n (%)# 23 (85.2) disease control rate, % (95% ci)§ 79.8 (69.6–87.7) durable disease control rate, % (95% ci)¶ 59.5 (48.3–70.1) time to response, median (range), months# 4.3 (2.1–21.4) kaplan-meier estimation of dor, median (95% ci), months# nr (15.5–ne) 6 months 88.5 (68.4–96.1) 12 months 83.8 (62.2–93.6) 24 months 56.6 (29.6–76.6) †orr per investigator assessment was 36.9% (95% ci, 26.6–48.1). ‡ne response includes the missing and unknown tumor response. §defined as the proportion of patients with complete response, partial response, stable disease, or non-partial response/non-progressive disease. ¶defined as the proportion of patients with complete response, partial response, stable disease, or non-partial response/non-progressive disease for ≥182 days without progressive disease. #data shown are for patients with response. ci, confidence interval; dor, duration of response; icr, independent central review; labcc, locally advanced basal cell carcinoma; ne, not evaluable; nr, not reached; orr, objective response rate. clinical activity • orr per icr was 32.1% (95% confidence interval [ci], 22.4–43.2) including six complete responses and 21 partial responses (table 3). – six (22.2%) responding patients had evidence of disease progression at the time of this analysis (figure 2). – the disease control rate was 79.8% (95% ci, 69.6–87.7). – the durable disease control rate was 59.5% (95% ci, 48.3–70.1). • as of data cutoff, median dor had not been reached. kaplan-meier estimates of dor were 83.8% (95% ci, 62.2–93.6) at 12 months and 56.6% (95% ci, 29.6–76.6) at 24 months (table 3). • median pfs was 16.5 months (95% ci, 8.6–21.4). kaplan-meier estimates of pfs were 56.7% (95% ci, 44.5−67.1) at 12 months and 31.7% (95% ci, 20.4–43.5) at 24 months (figure 3a). • median os had not been reached at the time these data were reported. kaplanmeier–estimated os at 24 months was 80.3% (95% ci, 69.0–87.9) (figure 3b). 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 p ro b a b ili ty o f p f s month b 84 32 27 26 23 15 12 9 9 7 4 3 2 0 0 0384148566476 17 a 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 p ro b a b ili ty o f o s month 84 65 65 60 56 51 48 44 40 32 21 15 9 0 0 0677172778083 53no. of patients at risk no. of patients at risk figure 3. kaplan-meier curves for pfs and os labcc, locally advanced basal cell carcinoma; pfs, progression-free survival; os, overall survival. safety • eighty-three (98.8%) patients experienced treatment-emergent adverse events (teaes) of any grade regardless of attribution. • the most common teaes of any grade were fatigue (n=26, 31.0%), diarrhea (n=20, 23.8%), pruritus (n=18, 21.4%), asthenia (n=17, 20.2%) and arthralgia (n=16, 19.0%). grade ≥3 teaes occurred in 44 (52.4%) patients (table 4). • fifteen (17.9%) patients discontinued treatment due to teaes of any grade. four (4.8%) patients died of teaes of any grade (table 4). • treatment-related aes (traes) were reported in 66 (78.6%) patients, with the most common being fatigue (n=21, 25%), asthenia (n=12, 14.3%), diarrhea (n=11, 13.1%), pruritis (n=11, 13.1%), nausea (n=9, 10.7%), decreased appetite (n=8, 9.5%) and hypothyroidism (n=8, 9.5%). • no grade ≥3 traes occurred in more than one patient or led to an outcome of death. • twenty-three (27.4%) patients experienced sponsor-identified immune-related aes (iraes) of any grade. grade ≥3 iraes occurred in nine (10.7%) patients. scan the qr code for co-author disclosures microsoft word 4. 719 proof done.docx skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 23 in-depth reviews characterizing the skin and gut microbiome of alopecia areata patients margit juhasz, md, msc,1 siwei chen, bs,2 arash khosrovi-eghbal, md, msc,3 chloe ekelem, md, mph,4 yessica landaverde,1 pierre baldi, phd,2 natasha atanaskova mesinkovska, md, phd1 1 department of dermatology, university of california, irvine, irvine, ca, usa 2 department of computer science, institute for genomics and bioinformatics, university of california, irvine, irvine, ca, usa 3 department of internal medicine, st. mary medical center ucla, long beach, ca, usa 4 department of dermatology, university of utah, salt lake city, ut, usa alopecia areata (aa) is an inflammatory, autoimmune, non-scarring type of hair loss resulting from immune attack of the hair follicle. disease severity ranges from characteristic bald patches of the scalp (aa), to the entire scalp (alopecia totalis/at), and even the entire body (alopecia universalis/au). aa affects up to 2% of the population, and is associated with high disease burden, decreased patient quality of life, as well as a high rate of psychological introduction background: alopecia areata (aa) is caused by an autoimmune attack of the hair follicle. the exact pathogenesis is unknown, but hypotheses include innate immunity imbalance, environmental exposures, genetic predisposition, and possibly the microbiome. the objective of this study was to characterize the skin and gut microbiome of aa patients, and compare microbial composition to healthy individuals. methods: this was a pilot, case-control study. scalp and fecal microbiome samples were collected from 25 aa patients, and 25 age, gender, and race-matched healthy controls in southern california with no significant difference in demographic characteristics. after library preparation and identification of bacterial and fungal taxonomy, multivariant analysis was performed to compare aa and healthy microbiomes. results: the aa scalp microbiome was significant for decreased clostridia and malasseziomycetes, and the gut microbiome was significant for decreased bacteroidia and increased bacilli (p<0.05) compared to healthy controls. conclusions: the composition of the aa bacterial and fungal, scalp and gut microbiome is significantly different than healthy individuals. future directions include using this data to characterize microbial changes associated with aa patient diet, relating to disease severity, and predicting disease progression, prognosis, and/or therapeutic response. abstract skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 24 comorbidity including depression and anxiety. the exact pathogenesis of aa remains elusive, however researchers hypothesize that it is a multifactorial disease with components including derangements in innate immunity, environmental exposure, genetic predisposition, and now possibly an altered microbiome.1 the microbiome is the community of commensal and pathogenic microorganisms (including bacteria and fungi) that live on and within our bodies, and contributes to human health through host defense mechanisms, inflammatory modulation and homeostasis mechanisms. current research suggests derangements in resident microbiota leads to inflammatory diseases of the gastrointestinal, cardiovascular, respiratory, endocrine and cutaneous systems. specific to dermatology and hair biology, recent animal studies suggest that the gut microbiome may play a role in the development of aa.2,3 with mounting evidence of the microbiome’s importance in various inflammatory disorders, we hypothesize that the skin and gut microbiome of aa patients differ significantly from healthy controls. understanding the composition of the aa microbiome will help to elucidate the role that commensal and pathogenic microbes may play in disease pathogenesis. this project is approved by the university of california, irvine (uc irvine) institutional review board. case-control study design is summarized in figure 1. we enrolled 25 patients with aa/at/au that had not received active treatment (including topicals, intralesional or systemic modalities) for at least four weeks, and 25 healthy, age and race-matched controls for a total of 50 participants. at the time of enrollment, participants could not have active or symptomatic gastrointestinal disease. enrollment occurred over the period of march to may 2018. subjects were all recruited from a single, tertiary medical center in southern california. demographic data and medical history were collected from each participant. skin (scalp) and gut (fecal) microbiome samples were collected from each patient for a total of 100 samples. the skin microbiome was collected by swabbing the entire scalp using culture swabstm ez collection and transport system (becton dickinson, franklin lakes, nj, usa) which were soaked in 0.15 m normal saline. the ends of the swabs were cut off and stored in 1.5 ml dnase/rnase-free microcentrifuge tubes (thermofisher scientific, waltham, ma, usa) at -80 oc until time of sample analysis. fecal samples were collected by giving each patient a sterile urine container (starplex scientific inc., etobicoke, ont, canada) to collect their stool at their convenience at home. patients were instructed to store the sample in their home freezer until transport to uc irvine was possible. once samples arrived, they were also stored at -80 oc. processing and analysis of microbiome samples was completed in conjunction with the uc irvine microbiome initiative. dna isolation was completed using the zymobiomicstm mini dna kit ht (zymoresearch, irvine, ca, usa). 16s rrna amplicon polymerase chain reaction (pcr) was performed targeting the full v5 region using the earth microbiome project (emp) primers barcoded 515 forward (515f) and 926 reverse (926r).4 the internal transcribed spacer (its) 2 region for fungal community composition was amplified using the its9f as a forward primer and the its4 as a barcoded reverse primer in a staggered design.5,6 the materials and methods skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 25 two libraries were combined and sequenced at the uc irvine genomics high throughput facility using a miseq version 3 chemistry (illumina, san diego, ca, usa) with a paired end 300 base pair (pe300) sequencing length. sequencing resulted in 24 million reads passing filter (of which 34% were phix control version 3 adapter-ligated library; llumina, san diego, ca, usa). final sequencing resulted in 94 bacterial and 65 fungal samples with reads. operational taxonomic units (otus) of bacterial sequences were identified and assigned taxonomic classification using the may 2013 greengenes database7 trained with original primer pairs used to amplify the 16s region. fungal sequences were assigned taxonomic classification using the unite database8 training the classifier with the whole database since its genes can be very variable. after barcode removal, de-multiplexing, and denoising, samples were imported into quantitative insights into microbial ecology (qiime) version 2.0.9 data interpretation and multi-variant statistical analysis was completed to analyze αand β-diversity and determine significant differences between aa and healthy skin and gut microbiomes by two authors (sc and mj). for each taxonomic level of bacterial and fungal data sets, the student t-test was performed to determine significant differences in the relative abundances of microbial content between the aa and healthy skin and gut microbiomes. demographics the average aa patient was female (72%), 40.28+/-14.68 years and caucasian (60%). there was no statistical differences in mean age, as well as gender or race/ethnicity distribution between the alopecia and healthy control groups. aa patients reported an increased prevalence of allergic rhinitis/seasonal allergies (40%), thyroid disease (including hyperand hypothyroidism; 32%), gastrointestinal disease (including irritable bowel syndrome, inflammatory bowel disease, gluten sensitivity, lactose intolerance, constipation or gastroesophageal reflux disease; 28%), and psychologic comorbidities (including depression and anxiety; 20%) compared to healthy controls. five patients with aa reported a history of “dermatitis”, including atopic dermatitis and contact dermatitis (table 1). figure 1. schematic representing the design of this case-control study. the majority of alopecia patients reported initially having aa subtype (88%) with their first episode 16±14 years prior to presentation at our clinical site. patients reported their most current alopecia episode started 7±11 years prior to presentation and results skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 26 was also of the aa subtype (56%). the most common prior treatments for alopecia included intralesional steroid injections (52%), topical minoxidil (24%), topical squaric acid (20%), and topical clobetasol (16%) (table 2). table 1. demographic data of alopecia patients (n=25) and healthy controls (n=25). alopecia areata healthy controls f m 72% 28% gender f m 68% 32% 40.28+/-14.68 age (years) 35.88+/-14.65 white asian hispanic black 60% 20% 12% 8% race white asian hispanic black 64% 16% 16% 4% allergic rhinitis/seasonal allergies thyroid disease gastrointestinal disease psychologic disorder asthma acne localized morphea 40% 32% 28% 20% 12% 8% 4% comorbid disease asthma gastrointestinal disease allergic rhinitis/seasonal allergies non-allergic rhinitis 12% 12% 8% 4% table 2. alopecia areata disease characterization (n=25) including a summary of previous treatment(s) used. it is important to note that patients had to discontinue treatment for at least four weeks prior to enrollment. alopecia areata disease presentation initial onset (years) 16+/-14 type of alopecia aa at/au ao 88% 8% 4% current episode (years) 7+/-11 type of alopecia aa at/au ao 56% 44% 0% previous treatments intralesional triamcinolone injections topical minoxidil topical squaric acid topical clobetasol investigational oral janus kinase inhibitor oral tofacitinib complementary and alternative medicine topical diphenylcyclopropenone topical ketoconazole shampoo oral corticosteroid platelet-rich plasma topical calcineurin inhibitor (eyebrows only) unknown systemic immunosuppressant 52% 24% 20% 16% 12% 12% 8% 8% 8% 8% 4% 4% 4% the aa microbiome is significantly different than healthy individuals analysis of the relative abundance of bacterial classes showed the aa scalp was significant for decreased class clostridia (p=0.03287), while the gut was significant for increased bacilli (p=0.007512). there was a trend to decreased bacteroidia in the aa gut, however significance was not reached (p=0.07645). prior results from animal models describe a significant increase in lactobacillales, an order in the class bacilli. lactobacillales was significantly increased in the aa gut microbiome compared to healthy (p=0.03262). there were no significant differences in the abundance of the other orders, bacillales or turicibacterales (p>0.05), in this class. the family lactobacillaceae and the genus lactobacillus were not significantly increased in the aa gut microbiome, which may be due to the large number of bacterial families and genera present in our small patient sample. the overall αand β-bacterial diversity was similar between aa patients and controls for both the skin and gut microbiome (figure 2). there was a significant decrease in relative abundance of fungal class malasseziomycetes (p=0.03506) on the aa scalp, with a non-significant decrease in fungal genus malassezia (p=0.0801). in addition, a non-significant increase in the class eurotiomycetes was also noted (p=0.0696). there were no significant changes in overall fungal diversity or relative abundance of fecal fungal classes. in contrast, the aa scalp fungal microbiome was significant for decreased α-diversity evenness and β-diversity compared to healthy (α-diversity p=0.049; β-diversity p=0.026), and α-diversity richness trended to significance (p=0.0567) (figure 3). skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 27 figure 2. the aa bacterial microbiome. there are no significant differences noted in αand β-diversity of the skin and fecal microbiome of aa patients compared to healthy controls. the aa scalp microbiome was significant for decreased clostridia, and the aa gut microbiome was significant for increased bacilli, most notably due to an increase in lactobacillales. figure 3. the aa fungal microbiome. there is a significant decrease in aa scalp microbiome αand β-diversity compared to healthy controls. no differences were noted in aa gut microbiome diversity. the aa scalp microbiome was significant for decreased malasseziomycetes. skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 28 our research describes the components of the human aa microbiome and how it may differ from a healthy individual. the data demonstrates that there is significant dysbiosis in the aa scalp and fecal microbiome compared to healthy controls. significantly increased gut lactobacillales in aa patients compared to healthy controls mimics results previously described in mouse models.10,11 the microbiome is the “new frontier” of medicine with evidence that commensal and pathogenic microbes living on and within our bodies play a role in the development of multiple inflammatory conditions. the healthy bacterial skin microbiome is made of multiple species including actinobacteria, bacteroides, firmicutes, and proteobacteria. with inflammatory skin disorders, such as atopic dermatitis, it has been shown that microbial diversity decreases, with increased colonization by staphylococcus species.12-14 we did not account for the diagnoses of atopic dermatitis and how this may have affected our aa skin microbiome. however, given that atopic dermatitis rarely affects the scalp, we believe that our microbiome results are not greatly affected. our cohort of aa patients demonstrated a significant decrease in fungal class malasseziomycetes on the scalp compared to healthy controls, of which the genus malassezia belongs. only 8% of aa patients were previously treated with topical ketoconazole, and it is unlikely that this affected results given that patients remained off treatment for at least four weeks before microbiome collection. the role of the skin microbiome has not been elucidated in aa. in male androgenetic alopecia (aga), malassezia overgrowth has been described in areas affected by hair loss on the scalp vertex. this increase in malassezia burden causes expression of oxidative stress genes, which may be related to aga disease pathogenesis.15 it is possible that changes in malassezia abundance, either increase or decrease, causes exogenous inflammation around and within the hair follicle, thus contributing to alopecia development. however, it is also possible that due to lack of a hair shaft within the follicle, aa patients may inherently have a decreased malassezia population due to an altered follicular environment. changes in the gut microbiome have been associated with increased prevalence of autoimmune diseases in developed countries. currently it is unknown what causes these microbiome changes, however hypotheses include environmental exposures, hygiene hypothesis, and the “western” diet high in inflammation-inducing fats and processed sugars. mice exposed to a western diet demonstrate changes in their gut microbial composition as soon as one day, with an increase in firmicutes and decrease in bacteroidetes phyla, with accompanying changes in metabolic pathways and gene expression leading to increased adiposity by two weeks. decreased bacteroidetes abundance leads to reduced production of anti-inflammatory short-chain fatty acids, dysregulation of colonic t-regulatory cells, as well as downstream effects on innate immune activation and tolerance. in humans, gut microbiota differences have been noted in patients with rheumatoid arthritis (decreased bifidobacterium and bacteroides) and atopic dermatitis (decreased lactobacillus) compared to healthy controls.2,16 a recent case series, supports our findings that the human microbiome plays a role in pathogenesis of aa. scalp and body hair regrowth was noted in two au patients after discussion skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 29 fecal microbiota transplant for recurrent clostridium difficile colitis. the long-term persistence of the transplant-induced hair regrowth suggests a fundamental change in the composition of the gut microbiome, and that prior gut dysbiosis may have contributed to the autoimmune alopecia.3 along those lines, gut monocolonization by lactobacillus murinus has been hypothesized as a contributing factor for aa in two mouse models. c5bl/6 mice were treated with vancomycin leading to increased abundance of gut l. murinus leading to a biotin-deficient alopecia phenotype. c3h mice prone to aa demonstrate increased baseline gut lactobacillus, causing aa development in healthy mouse skin grafts. after treatment with broad-spectrum antibiotics (ampicillin, neomycin, metronidazole and vancomycin), lactobacillus abundance was decreased and grafts did not develop aa.10,11 limitations of this study include small sample sizes. the restricted geographical location to southern california provided for a wellcontrolled study. previous studies have shown that there are geographical differences in microbiome samples and our results may not be generalizable throughout all geographic areas. the results from a cohort of aa patients located in southern california demonstrates significant dysbiosis of the skin and gut microbiome of aa patients compared to healthy controls. the cause(s) of dysbiosis in aa patients are not known, however it is believed that both environmental and genetic factors play a role in microbiome composition. changes in abundance of skin and gut bacteria and/or fungi may lead to inappropriate activation of the innate immune response, changes in tolerance, and ultimately systemic inflammation in predisposed individuals. this novel data may be used in the future to determine skin and gut microbiome changes associated with aa patient diet, disease severity, disease prognosis and progression, as well as response to targeted therapies. keywords: alopecia, alopecia areata, microbiome, bacteria, fungi, dysbiosis, inflammation acknowledgements: we would like to acknowledge the uc irvine microbiome initiative, specifically the laboratories of dr. jennifer martin and dr. katrina whiteson for their help with microbiome sample preparation, library creation, sequencing and identification of taxonomy. the work of swc and pb is in part supported by the national institutes of health (nih) grant gm123558-02s1 to pb. conflict of interest disclosures: dr. juhasz received partial monetary support from the la fondation la roche-posay grant and data analysis support from a university of california, irvine microbiome initiative pilot project award. ms. chan’s and dr. baldi’s research is partially support by a national institutes of health (nih) grant gm123558-02s1. funding: none corresponding author: margit juhasz, md, msc university of california, irvine department of dermatology 843 health sciences road irvine, ca, 92697 phone: 949-824-7103 email: mjuhasz@uci.edu references: 1. korta dz, christiano am, bergfeld w, et al. alopecia areata is a medical disease. j am acad dermatol 2018;78:832-4. 2. borde a, astrand a. alopecia areata and the gutthe link opens up for novel therapeutic interventions. expert opin ther targets 2018;22:503-11. conclusions skin january 2020 volume 4 issue 1 copyright 2020 the national society for cutaneous medicine 30 3. rebello d, wang e, yen e, lio pa, kelly cr. hair growth in two alopecia patients after fecal microbiota transplant. acg case rep j 2017;4:e107. 4. caporaso jg, lauber cl, walters wa, et al. ultrahigh-throughput microbial community analysis on the illumina hiseq and miseq platforms. isme j 2012;6:1621-4. 5. walters w, hyde er, berg-lyons d, et al. improved bacterial 16s rrna gene (v4 and v4-5) and fungal internal transcribed spacer marker gene primers for microbial community surveys. msystems 2016;1. 6. looby ci, maltz mr, treseder kk. belowground responses to elevation in a changing cloud forest. ecol evol 2016;6:1996-2009. 7. greengenes the 16s rrna gene database and tools. 2013. (accessed january 28, 2019, at http://greengenes.secondgenome.com/downloads. ) 8. 2018. unite. (accessed january 28, 2019, at https://unite.ut.ee/.) 9. qiime2. 2019. (accessed january 28, 2019, at https://qiime2.org/.) 10.hayashi a, mikami y, miyamoto k, et al. intestinal dysbiosis and biotin deprivation induce alopecia through overgrowth of lactobacillus murinus in mice. cell rep 2017;20:1513-24. 11.nair l, dai z, christiano am. gut microbiota plays a role in the development of alopecia areata. j investig dermatol 2017;137:s112. 12.bjerre rd, bandier j, skov l, engstrand l, johansen jd. the role of the skin microbiome in atopic dermatitis: a systematic review. br j dermatol 2017;177:1272-8. 13.rangel sm, paller as. bacterial colonization, overgrowth, and superinfection in atopic dermatitis. clin dermatol 2018;36:641-7. 14.wollina u. microbiome in atopic dermatitis. clin cosmet investig dermatol 2017;10:51-6. 15.chew eg, ho bs, ramasamy s, et al. comparative transcriptome profiling provides new insights into mechanisms of androgenetic alopecia progression. br j dermatol 2017;176:265-9. 16.maslowski km, mackay cr. diet, gut microbiota and immune responses. nat immunol 2011;12:59. deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, in moderate to severe plaque psoriasis: evaluation of lipid parameters in the phase 3 poetyk pso-1 and pso-2 trials mark lebwohl,1 bruce strober,2 misti linaberry,3 kim hoyt,3 subhashis banerjee,3 renata m kisa,3 nehal n mehta4 1icahn school of medicine at mount sinai, new york, ny, usa; 2yale university school of medicine, new haven, and central connecticut dermatology, cromwell, ct, usa; 3bristol myers squibb, princeton, nj, usa; 4the george washington university school of medicine, washington, dc, usa presented at the winter clinical dermatology conference hawaii®, january 13-18, 2023, kohala coast, hi, and winter clinical miamitm, february 17-20, 2023, miami, fl this is an encore of the 2022 fall clinical dermatology conference poster email for mark lebwohl, md: lebwohl@aol.com this poster may not be reproduced without written permission from the authors. synopsis • tyrosine kinase 2 (tyk2) is an intracellular enzyme that mediates signaling of cytokines (interleukin-23 and type i interferons) involved in psoriasis pathogenesis1 • deucravacitinib, an oral, selective, allosteric tyk2 inhibitor, is approved by the us food and drug administration for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy2 based on results from the phase 3 poetyk pso-1 and pso-2 trials3,4 • plaque psoriasis is associated with hypertriglyceridemia and metabolic syndrome,5,6 and the frequency of hypertriglyceridemia increases with plaque psoriasis severity7 — triglycerides ≥150 mg/dl are among the clinical characteristics used to identify patients with metabolic syndrome8 — the american academy of dermatology recommends that patients with plaque psoriasis be informed about their increased risk of metabolic syndrome and have frequent lipid screenings, especially when the disease is severe5 • in clinical trials enrolling patients with moderate to severe plaque psoriasis, treatment with deucravacitinib was associated with slight increases (~10 mg/dl) in mean triglyceride levels in the absence of any changes in mean cholesterol levels2 • in the absence of atherosclerotic cardiovascular disease (ascvd) and diabetes mellitus, the american academy of cardiology9 recommends: — diet and lifestyle optimization in adults with fasting triglycerides ≥150 mg/dl and <500 mg/dl — consideration of initiation or intensification of statin therapy in adults with persistently elevated fasting triglycerides ≥150 mg/dl and <500 mg/dl and a calculated ascvd risk ≥5% objective • to report changes in lipid parameters in patients enrolled in poetyk pso-1 and pso-2 and treated with: — placebo, deucravacitinib, or apremilast over 16 weeks — deucravacitinib continuously for 52 weeks methods study designs • poetyk pso-1 (nct03624127) and pso-2 (nct03611751) were phase 3, 52-week, double-blind, randomized, placeboand active comparator (apremilast)-controlled trials conducted globally (figure 1) — enrolled patients with moderate to severe plaque psoriasis (psoriasis area and severity index [pasi] ≥12; static physician’s global assessment [spga] ≥3; body surface area involvement ≥10%) were randomized 1:2:1 to oral placebo, deucravacitinib 6 mg once daily, or apremilast 30 mg twice daily during weeks 0–16 — blinded treatment switches occurred at week 16 and week 24 • patients receiving placebo crossed over to deucravacitinib at week 16 • patients receiving apremilast who failed to meet trial-specific efficacy thresholds in poetyk pso-1 (≥50% reduction from baseline in pasi [pasi 50]) and in poetyk pso-2 (≥75% reduction from baseline in pasi [pasi 75]) were switched to deucravacitinib at week 24 • patients receiving deucravacitinib who achieved pasi 75 at week 24 in poetyk pso-2 were re-randomized (1:1) to continue deucravacitinib or to switch to placebo (withdrawal); patients receiving apremilast who achieved pasi 75 were switched to placebo figure 1. poetyk pso-1 and pso-2 study designs poetyk pso-1 (n = 666) deucravacitinib 6 mg qdplacebo (n = 166) deucravacitinib 6 mg qd<pasi 50 apremilast 30 mg bid≥pasi 50 titrate* 1 :2 :1 r an d om iz at io n weeks coprimary endpoints: pasi 75 and spga 0/1 for deucravacitinib vs placebo at week 16 16 24 520 deucravacitinib 6 mg qd (n = 332) primary endpoint apremilast 30 mg bida (n = 168) poetyk pso-2 (n = 1020) deucravacitinib 6 mg qdplacebo (n = 255) deucravacitinib 6 mg qd (n = 511) deucravacitinib 6 mg qd deucravacitinib 6 mg qd deucravacitinib 6 mg qd deucravacitinib 6 mg qd placebob apremilast 30 mg bida (n = 254) 1 :2 :1 r an d om iz at io n weeks 16 24 520 1:1 deucravacitinib 6 mg qdplacebob primary endpoint <pasi 75 ≥pasi 75 <pasi 75 ≥pasi 75 from armstrong aw, et al. deucravacitinib versus placebo and apremilast in moderate to severe plaque psoriasis: efficacy and safety results from the 52-week, randomized, double-blinded, placebocontrolled phase 3 poetyk pso-1 trial. j am acad dermatol. 2023;88:29-39. this work is licensed under a creative commons attribution license (cc by-nc-nd 4.0). https://creativecommons.org/ licenses/by-nc-nd/4.0/. from strober b, et al. deucravacitinib versus placebo and apremilast in moderate to severe plaque psoriasis: efficacy and safety results from the 52-week, randomized, double-blinded, phase 3 poetyk pso-2 trial. j am acad dermatol. 2023;88:40-51. this work is licensed under a creative commons attribution license (cc by-nc-nd 4.0). https://creativecommons.org/licenses/by-nc-nd/4.0/. aapremilast was titrated from 10 mg qd to 30 mg bid over the first 5 days of dosing. bupon relapse (≥50% loss of week 24 pasi percentage improvement from baseline), patients were to be switched to deucravacitinib 6 mg qd. bid, twice daily; pasi, psoriasis area and severity index; pasi 50, ≥50% reduction from baseline in pasi; pasi 75, ≥75% reduction from baseline in pasi; qd, once daily; spga 0/1, static physician's global assessment score of 0 (clear) or 1 (almost clear) with a ≥2-point improvement from baseline. lipid assessments • mean total cholesterol, high-density lipoprotein (hdl) cholesterol, low-density lipoprotein (ldl) cholesterol, and triglycerides are reported: — at baseline and week 16 in patients treated with placebo, deucravacitinib, and apremilast — over multiple time points from baseline to week 52 in patients who received continuous deucravacitinib • changes in cholesterol and triglycerides on laboratory analyses are presented as grade shifts per common terminology criteria for adverse events (ctcae) version 5 (table 1): — from baseline to week 16 in patients treated with placebo, deucravacitinib, and apremilast — from baseline to week 52 in patients who received continuous deucravacitinib treatment table 1. ctcae grades for hypercholesterolemia and hypertriglyceridemia grade total cholesterol range triglyceride range 0 ≤ulna <150 mg/dl (<1.71 mmol/l) 1 >uln-300 mg/dl; >uln-7.75 mmol/l 150-300 mg/dl (1.71-3.42 mmol/l) 2 >300-400 mg/dl; >7.75-10.34 mmol/l >300-500 mg/dl (>3.42-5.7 mmol/l) 3 >400-500 mg/dl; >10.34-12.92 mmol/l >500-1000 mg/dl (>5.7-11.4 mmol/l) 4 >500 mg/dl; >12.92 mmol/l >1000 mg/dl (>11.4 mmol/l); life-threatening consequences adefined in these analyses as 200 mg/dl. ctcae, common terminology criteria for adverse events; uln, upper limit of normal. results patient population • a total of 666 and 1020 patients were randomized in the poetyk pso-1 and pso-2 trials, respectively, and were included in this analysis changes in lipid parameters from baseline to week 16 • baseline means for total cholesterol, hdl cholesterol, ldl cholesterol, and triglycerides were similar across treatment groups (table 2) • mean changes in total cholesterol, hdl cholesterol, and ldl cholesterol were small across treatment groups and not clinically meaningful (table 2) • baseline mean triglyceride levels were near the upper limit of normal (uln; 150 mg/dl) across treatment groups (table 2) • there were slight increases (~10 mg/dl) in mean triglyceride levels with deucravacitinib treatment (table 2) table 2. changes in lipid parameters from baseline to week 16 (pooled poetyk pso-1 and pso-2) parameter placebo deucravacitinib 6 mg qd apremilast 30 mg bid n mean (sd/sea) n mean (sd/sea) n mean (sd/sea) total cholesterol, mg/dlb baseline 419 189.4 (39.03) 842 189.1 (39.24) 422 190.1 (37.15) week 16 357 190.4 (38.55) 755 192.5 (40.42) 369 187.8 (36.70) change 357 -0.1 (1.27) 755 2.6 (0.97) 369 -2.8 (1.26) hdl cholesterol, mg/dl baseline 419 49.5 (15.50) 842 50.4 (15.16) 422 50.5 (17.23) week 16 357 48.5 (13.49) 755 51.7 (15.80) 369 51.9 (18.46) change 357 -0.9 (0.39) 755 0.9 (0.28) 369 0.5 (0.38) ldl cholesterol, mg/dl baseline 419 110.8 (33.77) 842 109.8 (34.90) 421 111.5 (32.32) week 16 347 112.8 (33.37) 733 110.2 (35.97) 360 109.2 (32.37) change 347 0.7 (1.15) 733 -0.2 (0.84) 359 -2.5 (1.11) triglycerides, mg/dl baseline 419 149.5 (106.77) 842 146.6 (92.04) 422 145.9 (93.81) week 16 357 149.8 (88.95) 755 157.1 (104.02) 369 137.7 (80.80) change 357 0.4 (4.77) 755 10.3 (3.15) 369 -6.8 (3.24) asd is reported for baseline and week 16 means; se is reported for mean change from baseline. btotal cholesterol = hdl + ldl + 20% triglycerides. bid, twice daily; hdl, high-density lipoprotein; ldl, low-density lipoprotein; qd, once daily; sd, standard deviation; se, standard error. • worsening of hypercholesterolemia was observed with comparable frequency among patients treated with placebo, deucravacitinib, and apremilast (10.6%, 11.7%, and 8.4%, respectively); nearly all shifts were 1 grade (table 3) • most deucravacitinib-treated patients maintained the same or shifted to a lower grade of hypercholesterolemia from baseline to week 16 (table 3) table 3. shifts in grade of hypercholesterolemia from baseline to week 16 (pooled poetyk pso-1 and pso-2) parameter baseline grade grade at week 16, n (%) total patients0 1 2 3 4 placebo 0 182 (82.7) 38 (17.3) 0 (0.0) 0 (0.0) 0 (0.0) 220 1 31 (22.8) 105 (77.2) 0 (0.0) 0 (0.0) 0 (0.0) 136 2 0 (0.0) 1 (100.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 3 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 4 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 total 213 144 0 0 0 357 deucravacitinib 6 mg qd 0 387 (82.5) 81 (17.3) 1 (0.2) 0 (0.0) 0 (0.0) 469 1 64 (22.7) 212 (75.2) 6 (2.1) 0 (0.0) 0 (0.0) 282 2 0 (0.0) 4 (100.0) 0 (0.0) 0 (0.0) 0 (0.0) 4 3 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 4 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 total 451 297 7 0 0 755 apremilast 30 mg bid 0 205 (87.2) 30 (12.8) 0 (0.0) 0 (0.0) 0 (0.0) 235 1 41 (31.1) 90 (68.2) 1 (0.8) 0 (0.0) 0 (0.0) 132 2 0 (0.0) 2 (100.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 3 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 4 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 total 246 122 1 0 0 369 light pink shading indicates a shift of 1 grade; dark pink shading indicates a shift of >1 grade. bid, twice daily; qd, once daily. • grade ≥3 hypertriglyceridemia occurred in several patients in each treatment group at week 16 (table 4) • worsening shifts in hypertriglyceridemia >1 grade were observed in 1.4%, 1.2%, and 0.3% of patients treated with placebo, deucravacitinib, and apremilast, respectively (table 4) • most deucravacitinib-treated patients maintained the same or shifted to a lower grade of hypertriglyceridemia from baseline to week 16 (table 4) — of the 34 deucravacitinib-treated patients with grade 2 or 3 hypertriglyceridemia at baseline, 19 improved to grade 0 or 1 at week 16 • no patient exhibited pancreatitis or a major adverse cardiovascular event associated with grade 4 hypertriglyceridemia • no adverse event related to increased triglycerides was reported as serious or led to treatment discontinuation table 4. shifts in grade of hypertriglyceridemia from baseline to week 16 (pooled poetyk pso-1 and pso-2) parameter baseline grade grade at week 16, n (%) total patients0 1 2 3 4 placebo 0 195 (86.7) 26 (11.6) 4 (1.8) 0 (0.0) 0 (0.0) 225 1 37 (35.9) 56 (54.4) 9 (8.7) 1 (1.0) 0 (0.0) 103 2 4 (15.4) 14 (53.8) 7 (26.9) 1 (3.8) 0 (0.0) 26 3 0 (0.0) 2 (100.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 4 0 (0.0) 0 (0.0) 0 (0.0) 1 (100.0) 0 (0.0) 1 total 236 98 20 3 0 357 deucravacitinib 6 mg qd 0 381 (78.2) 99 (20.3) 6 (1.2) 1 (0.2) 0 (0.0) 487 1 66 (28.3) 135 (57.9) 31 (13.3) 1 (0.4) 0 (0.0) 233 2 2 (6.7) 16 (53.3) 7 (23.3) 4 (13.3) 1 (3.3) 30 3 0 (0.0) 1 (25.0) 2 (50.0) 1 (25.0) 0 (0.0) 4 4 0 (0.0) 0 (0.0) 1 (100.0) 0 (0.0) 0 (0.0) 1 total 449 251 47 7 1 755 apremilast 30 mg bid 0 210 (87.5) 29 (12.1) 1 (0.4) 0 (0.0) 0 (0.0) 240 1 42 (40.4) 56 (53.8) 6 (5.8) 0 (0.0) 0 (0.0) 104 2 2 (8.7) 12 (52.2) 7 (30.4) 2 (8.7) 0 (0.0) 23 3 0 (0.0) 0 (0.0) 2 (100.0) 0 (0.0) 0 (0.0) 2 4 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 total 254 97 16 2 0 369 light pink shading indicates a shift of 1 grade; dark pink shading indicates a shift of >1 grade. bid, twice daily; qd, once daily. changes in lipid parameters in patients treated with deucravacitinib continuously from baseline to week 52 • mean changes in total cholesterol, hdl cholesterol, ldl cholesterol, and triglycerides among patients treated with deucravacitinib continuously for 52 weeks were small and not clinically meaningful (figure 2) • the exposure-adjusted incidence rate (eair) for “blood cholesterol increased” as an adverse event over weeks 0-52 was 0.2/100 person-years (py) with deucravacitinib compared with 0.4/100 py with placebo and 0 with apremilast • the eair for “blood triglycerides increased” as an adverse event over weeks 0-52 was 1.0/100 py with deucravacitinib compared with 0.4/100 py with placebo and 1.3/100 py with apremilast • no patient discontinued deucravacitinib due to a lipid-related adverse event figure 2. change in lipid parameters among patients treated continuously with deucravacitinib during weeks 0-52 (pooled poetyk pso-1 and pso-2) 0.5 0.9 1.5 1.5 -30 -20 -10 0 10 20 30 0 8 16 24 52 hdl cholesterol 692 642 609 577 523n = m e an ± s e , m g/ d l baseline mean (sd) = 49.7 (14.59) 1.8 2.2 3.7 3.3 0 10 20 30 40 50 0 8 16 24 52 total cholesterola 692 642 609 577 523n = baseline mean (sd) = 189.0 (39.16) m e an ± s e , m g/ d l weeks weeks weeks weeks 12.0 10.7 13.2 13.1 0 10 20 30 40 50 60 70 80 90 100 0 8 16 24 52 692 642 609 577 523 triglyceridesb n = baseline mean (sd) = 148.4 (93.76) m e an ± s e , m g/ d l -0.5 0.1 -0.7 -30 -20 -10 0 10 20 30 0 8 16 24 52 ldl cholesterol 692 623 591 558 507n = baseline mean (sd) = 110.0 (35.17) m e an ± s e , m g/ d l -0.6 sotyktutm us prescribing information values at weeks 16 and 52 reflect a mixed population including crossover patients2,b atotal cholesterol = hdl + ldl + 20% triglycerides. bthe values presented here are limited to patients enrolled in poetyk pso-1 and pso-2 who received deucravacitinib continuously for 52 weeks. sotyktu™ (deucravacitinib) prescribing information notes that mean triglyceride levels increased by 10.3 mg/dl and by 9.1 mg/dl during the 16-week and 52-week treatment periods, respectively, in the combined population from the 2 studies. the label values were derived from all patients who were taking deucravacitinib at week 16 or at week 52 from both poetyk pso-1 and pso-2 studies. some of the latter had received placebo or apremilast in a previous treatment period per the individual study designs. hdl, high-density lipoprotein; ldl, low-density lipoprotein; sd, standard deviation; se, standard error. • most patients treated with deucravacitinib continuously for 52 weeks maintained the same or shifted to a lower grade of hypercholesterolemia from baseline to week 52 (table 5) — there was one 2-grade increase in hypercholesterolemia from baseline to week 52 table 5. shifts in grade of hypercholesterolemia among patients treated continuously with deucravacitinib during weeks 0-52 (pooled poetyk pso-1 and pso-2) parameter baseline grade grade at week 52, n (%) total patients0 1 2 3 4 deucravacitinib 6 mg qd 0 253 (80.8) 59 (18.8) 1 (0.3) 0 (0.0) 0 (0.0) 313 1 45 (21.4) 161 (76.7) 4 (1.9) 0 (0.0) 0 (0.0) 210 2 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 3 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 4 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 total 298 220 5 0 0 523 light pink shading indicates a shift of 1 grade; dark pink shading indicates a shift of >1 grade. qd, once daily. • most patients treated with deucravacitinib continuously for 52 weeks maintained the same or shifted to a lower grade of hypertriglyceridemia from baseline to week 52 (table 6) — grade ≥3 hypertriglyceridemia events were rare and were limited to those with elevated triglycerides at baseline — shifts >1 grade were observed in 1.9% of patients table 6. shifts in grade of hypertriglyceridemia among patients treated continuously with deucravacitinib during weeks 0-52 (pooled poetyk pso-1 and pso-2) parameter baseline grade grade at week 52, n (%) total patients0 1 2 3 4 deucravacitinib 6 mg qd 0 241 (73.0) 84 (25.5) 5 (1.5) 0 (0.0) 0 (0.0) 330 1 49 (29.9) 97 (59.1) 14 (8.5) 4 (2.4) 0 (0.0) 164 2 1 (4.0) 10 (40.0) 12 (48.0) 1 (4.0) 1 (4.0) 25 3 0 (0.0) 2 (66.7) 0 (0.0) 1 (33.3) 0 (0.0) 3 4 0 (0.0) 0 (0.0) 1 (100.0) 0 (0.0) 0 (0.0) 1 total 291 193 32 6 1 523 light pink shading indicates a shift of 1 grade; dark pink shading indicates a shift of >1 grade. qd, once daily. conclusions • in the phase 3 poetyk pso-1 and pso-2 trials, mean changes in the lipid panel from baseline to week 16 were minimal across the placebo, deucravacitinib, and apremilast groups, and none was clinically meaningful — a 10.3 mg/dl increase in mean triglyceride levels from a baseline mean of 146.6 mg/dl in the deucravacitinib group was accompanied by very few worsening shifts in hypertriglyceridemia >1 grade per ctcae • a large majority of patients treated continuously with deucravacitinib for 52 weeks maintained their baseline grade or shifted to a lower grade of hypercholesterolemia or hypertriglyceridemia at week 52 — fewer than 2% of patients had worsening shifts >1 grade from baseline to week 52 — no patient discontinued deucravacitinib due to a lipid-related adverse event • clinical guidelines recommend diet and lifestyle optimization for most low-risk adults with fasting triglycerides ≥150 mg/dl and <500 mg/dl, with consideration of initiation or intensification of pharmacotherapy in those with persistent elevations and a calculated ascvd risk ≥5%9 — these guidelines would apply to most patients with moderate to severe plaque psoriasis due to the high incidence of hypertriglyceridemia/metabolic syndrome in these patients references 1. burke jr, et al. sci trans med. 2019;11:eaaw1736. 2. sotyktu™ (deucravacitinib) [package insert]. princeton, nj: bristol-myers squibb company; september 2022. 3. armstrong aw, et al. j am acad dermatol. 2023;88:29-39. 4. strober b, et al. j am acad dermatol. 2023;88:40-51. 5. elmets ca, et al. j am acad dermatol. 2019;80:1073-1113. 6. teklu m, et al. j am acad dermatol. 2021;84:1329-1338. 7. langan sm, et al. j invest dermatol. 2012;132:556-562. 8. grundy sm, et al. circulation. 2004;109:433-438. 9. virani ss, et al. j am coll cardiol. 2021;78:960-993. acknowledgments • this study was sponsored by bristol myers squibb • writing and editorial assistance was provided by liz rockstein, phd, of peloton advantage, llc, an open health company, parsippany, nj, usa, funded by bristol myers squibb • the authors thank the patients and investigators who participated in these trials disclosures • ml: research funds on behalf of mount sinai: abbvie, amgen, arcutis, avotres, boehringer ingelheim, dermavant, eli lilly, incyte, janssen, ortho dermatologics, regeneron, and ucb; consultant: aditum bio, almirall, altrubio, anaptysbio, arcutis, arena, aristea, arrive technologies, avotres, biomx, boehringer ingelheim, brickell biotech, bristol myers squibb, cara therapeutics, castle biosciences, corevitas’ (corrona) psoriasis registry, dermavant, dr reddy’s laboratories, evelo biosciences, evommune, forte biosciences, helsinn therapeutics, hexima, leo pharma, meiji seika pharma, mindera, pfizer, seanergy, and verrica • bs: consultant (honoraria): abbvie, almirall, amgen, arcutis, arena, aristea, asana, boehringer ingelheim, bristol myers squibb, connect biopharma, dermavant, eli lilly, equillium, glaxosmithkline, immunic therapeutics, janssen, leo pharma, maruho, meiji seika pharma, mindera, novartis, ortho dermatologics, pfizer, regeneron, sanofi genzyme, sun pharma, ucb, ventyxbio, and vtv therapeutics; speaker: abbvie, eli lilly, janssen, and sanofi genzyme; co-scientific director (consulting fee): corevitas' (corrona) psoriasis registry; investigator: abbvie, cara therapeutics, corevitas' (corrona) psoriasis registry, dermavant, dermira, and novartis • ml, kh, sb, and rmk: employees and shareholders: bristol myers squibb • nnm: consultant: abcentra, amgen, and novartis skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 920 brief article bullous eruption after off-label use of topical tirbanibulin on the chest jessica kim, oms-iii, bs1, onyebuchi neita, pa-c2, joseph m. dyer, do1 1 philadelphia college of osteopathic medicine, suwanee, ga 2 epiphany dermatology, peachtree city, ga actinic keratoses are premalignant skin growths, may progress to squamous cell carcinoma, and most commonly affect the sun-exposed regions of the body like the face, scalp, extensor forearms, and dorsal hands.1 current topical field-directed medications include 5-fluorouracil, imiquimod, and diclofenac sodium1, with clearance rates around 75%2, 85%3, and 58%3 respectively. tirbanibulin is a fairly new topical treatment for actinic keratosis approved by the fda in december 2020. advertised as a first-inclass topical with high efficacy and fewer adverse effects compared to alternative field therapies, its proposed molecular target is by indirect inhibition of src.4 this decreases microtubule polymerization and src kinase signaling, effectively downregulating the growth of human keratinocytes and inducing apoptosis.5,6 recommended usage of tirbanibulin is once daily application to the face or scalp, to an area up to 25 cm2, for five consecutive days.7 excipients in the commercially available formulation of tirbanibulin 1% ointment include propylene glycol and glycerol monostearate 40-55.8 a 56-year-old caucasian female with a history of actinic keratoses and cutaneous squamous cell carcinoma presented for reevaluation of scattered actinic keratoses on the upper chest status post application of tirbanibulin 1% ointment once daily for 5 days. with prior actinic keratoses treated with cryotherapy, tirbanibulin was the first fielddirected topical agent used by the patient. the patient reported the appearance of small vesicles on day 3 of application which worsened by day 5. she noted pruritus and denied pain. she reported meticulous sun avoidance during the treatment duration. the patient denies a history of allergic contact abstract tirbanibulin 1% ointment (klisyri), an fda-approved topical treatment for actinic keratosis, is advertised to serve as a first-in-class topical with high efficacy and low adverse effects compared to other field therapies. we report a case of severe bullous eruption associated with application of tirbanibulin in an adult female. though application of tirbanibulin did resolve the actinic keratoses on the patient’s chest, the severe local skin reaction precludes future use of tirbanibulin in her case. introduction case report skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 921 dermatitis, rash secondary to any topical medicaments, history of lupus erythematosus, porphyria, or polymorphous light eruption. examination revealed a well-demarcated erythematous plaque studded with tense vesicles and bullae of her upper chest (figure 1). figure 1. erythema and brisk vesiculation on the upper chest following tirbanibulin application. management included drainage of larger bullae with sterile needle and application of triamcinolone 0.1% cream twice daily for 2 weeks. the patient reported resolution of symptoms and bullae by 2 weeks. at her follow-up visit 2 months later, there was mild postinflammatory erythema without scarring. no actinic keratoses were noted in the treatment field at that time. in the phase 1 study of tirbanibulin ointment with 30 participants, no participants experienced any vesiculation or pustulation post application to their forearm.9 in the phase 2 study with 168 participants applying tirbanibulin to their face and scalp, 5 patients experienced minimal or mild vesiculation and pustulation, as rated by investigators; no moderate or severe vesicular reactions were noted.9 in the phase 3 study with 702 participants, 353 patients received tirbanibulin and 349 received a placebo, 10% experienced application-site pain.5 interestingly, only 1% (2/353) of patients experienced severe vesiculation or pustulation while erythema (91%) and flaking or scaling (82%) were common side-effects.5 in trial 1 and 2 of phase 3, there was a pooled complete clearance rate of actinic keratoses among 49% of participants compared to a 9% clearance rate in the placebo group at day 57.5 in trial 1 and 2 of phase 3, there was a pooled partial clearance rate among 72% of participants compared to 18% in the placebo group at day 57.5 though the clearance rate with tirbanibulin is not as high as other field-directed topicals7, this patient did experience complete clearance of her actinic keratoses. however, she fell in the minority of patients (<1%) who experience severe adverse skin reactions. the reason for this is unclear. one hypothesis to explore is whether the skin of the chest metabolizes the medicine differently than the face or scalp. other explanations for her intense vesiculation include an idiosyncratic sensitivity to tirbanibulin’s pharmacologic effect or a brisk allergic contact dermatitis to one of the ointment’s excipients. though tirbanibulin ointment is generally associated with mild adverse reactions8 and increased user compliance due to its short duration of application, clearance rates may be lower than other topical field-directed therapies for actinic keratoses.7 despite the discussion conclusion skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 922 low percentage (<1%)7 of patients who experience severe bullous reactions, patients who are using tirbanibulin ointment in offlabel locations or in areas greater than 25 cm2 should be counseled to report atypical side effects to their healthcare provider. conflict of interest disclosures: none funding: none corresponding author: jessica kim, oms-iii, bs philadelphia college of osteopathic medicine suwanee, ga email: jk0493@pcom.edu references: 1. marques e, chen tm. actinic keratosis. [updated 2022 may 9]. in: statpearls [internet]. treasure island (fl): statpearls publishing; 2022 jan-. available from: https://www.ncbi.nlm.nih.gov/books/nbk557401/ 2. elsenpeter, hannah m. s. md; giammar, lauren md. is topical 5-fluorouracil or combination 5fluorouracil and cryotherapy more effective than cryotherapy alone for the treatment of actinic keratosis?. evidence-based practice 25(7):p 2728, july 2022. | doi: 10.1097/ebp.0000000000001619 3. dianzani c, conforti c, giuffrida r, corneli p, di meo n, farinazzo e, moret a, magaton rizzi g, zalaudek i. current therapies for actinic keratosis. int j dermatol. 2020 jun;59(6):677684. doi: 10.1111/ijd.14767. epub 2020 feb 3. pmid: 32012240. 4. gilaberte y, fernández-figueras mt. tirbanibulin: review of its novel mechanism of action and how it fits into the treatment of actinic keratosis. actas dermosifiliogr. 2022 jan;113(1):58-66. english, spanish. doi: 10.1016/j.ad.2021.07.006. epub 2021 aug 2. pmid: 35249711. 5. blauvelt a, kempers s, lain e, schlesinger t, tyring s, forman s, ablon g, martin g, wang h, cutler dl, fang j, kwan mr; phase 3 tirbanibulin for actinic keratosis group. phase 3 trials of tirbanibulin ointment for actinic keratosis. n engl j med. 2021 feb 11;384(6):512-520. doi: 10.1056/nejmoa2024040. pmid: 33567191. 6. gilchrest ba. tirbanibulin: a new topical therapy for actinic keratoses with a novel mechanism of action and improved ease of use. clin pharmacol drug dev. 2021 oct;10(10):11261129. doi: 10.1002/cpdd.1024. pmid: 34612001. 7. geer k. tirbanibulin (klisyri) for the treatment of actinic keratosis. am fam physician. 2021 nov 1;104(5):519-520. pmid: 34783508. 8. dao dd, sahni vn, sahni dr, balogh ea, grada a, feldman sr. 1% tirbanibulin ointment for the treatment of actinic keratoses. ann pharmacother. 2022 apr;56(4):494-500. doi: 10.1177/10600280211031329. epub 2021 jul 23. pmid: 34301153; pmcid: pmc8899810. 9. kempers s, dubois j, forman s, poon a, cutler e, wang h, cutler d, fang j, kwan r. tirbanibulin ointment 1% as a novel treatment for actinic keratosis: phase 1 and 2 results. j drugs dermatol. 2020 nov 1;19(11):1093-1100. doi: 10.36849/jdd.2020.5576. pmid: 33196758. previously presented at 28th eadv congress 2019presented at the 5th annual 2020 pa & np fall clinical dermatology conference, orlando, florida, november 13–15, 2020 patients • ≥18 years with moderate to severe pso ≥6 months, pasi ≥12, ≥10% body surface area (bsa) affected, and physician’s global assessment (pga) ≥3 on a 5-point scale. • candidates for systemic pso therapy, phototherapy and/ or photochemotherapy. • exclusion criteria: previous treatment with czp or >2 biologics; history of primary failure to any biologic or secondary failure to >1 biologic; erythrodermic, guttate or generalized pso types; current or history of chronic or recurrent viral, bacterial or fungal infections. study assessments and statistical analyses • patients were assessed through weeks 0–144 for: – pasi 75 (≥75% improvement from baseline) – pasi 90 (≥90% improvement from baseline) – dlqi 0/1 (dermatology life quality index score of 0/1 [remission]) • estimates of responder rate reflect the simple average response across the multiply imputed data sets, with missing data imputed using markov chain monte carlo (mcmc) methodology. results patient population • at week 0, 175 patients were randomized to czp 400 mg q2w and 186 patients to czp 200 mg q2w. • baseline characteristics were balanced across treatment groups (table 1). clinical response to week 144 • initial week 16 responder rates were durable through to week 48 for both czp 400 mg q2w and czp 200 mg q2w (figure 2). • in patients initially randomized to czp 200 mg q2w, pasi 75, pasi 90 and dlqi 0/1 responder rates were sustained for a further two years to week 144 (figure 2). • in patients initially randomized to czp 400 mg q2w, clinical response gradually declined following dose reduction to czp 200 mg q2w at week 48 (figure 2). background • plaque psoriasis (pso) is an inflammatory disease that affects around 3% of adults in the united states.1,2 • treatment options for pso include phototherapy/ photochemotherapy, topical treatments, systemic agents and biologics.3–6 • given the chronic nature of pso, sustained treatment efficacy over the long-term is highly important. however, loss of response over time has previously been associated with biologics in pso.7 • certolizumab pegol (czp) is an fc-free, pegylated, anti-tumor necrosis factor (tnf) which has led to durable clinical improvements in patients with pso over two years of treatment.8,9 • here, we report the clinical responses of pso patients over three years of czp treatment, using data from the cimpasi-1 and cimpasi-2 phase 3 trials. methods study design • data were pooled for patients enrolled in two phase 3 trials, cimpasi-1 (nct02326298) and cimpasi-2 (nct02326272) (figure 1). • this analysis includes all patients who were randomized to czp 400 mg every two weeks (q2w) or czp 200 mg q2w at week 0 (intent-to-treat population). • on entry to the open-label phase, all patients were initially treated with czp 200 mg q2w; subsequent dosing adjustment based on psoriasis area severity index (pasi) response was either mandatory or at the discretion of the investigator (figure 1). references 1. kurd sk. et al. j am acad dermatol 2009;60:218–24; 2. rachakonda td. et al. j am acad dermatol 2014;70:512–6; 3. elmets ca. et al. j am acad dermatol 2019; 4. menter a. et al. j am acad dermatol 2009;60:643–59; 5. menter a. et al. j am acad dermatol 2009; 61:451–85; 6. menter a. et al. j am acad dermatol 2019;80:1029–72; 7. levin ec. et al. j dermatol treat 2014;25:78–82; 8. gottlieb ab. et al. j am acad dermatol 2018;79:302–14; 9. gordon k. et al. aad 2019. author contributions substantial contributions to study conception/design, or acquisition/analysis/interpretation of data: kg, rbw, abg, ab, dt, cl, yp, mb, sk, ca, kr; drafting of the publication, or revising it critically for important intellectual content: kg, rbw, abg, ab, dt, cl, yp, mb, sk, ca, kr; final approval of the publication: kg, rbw, abg, ab, dt, cl, yp, mb, sk, ca, kr. author disclosures kg: honoraria and or research support from: abbvie, almirall, amgen, boehringer ingelheim, bristol-myers squibb, celgene, dermira inc., eli lilly, janssen, novartis, pfizer, sun pharma, and ucb pharma; rbw: consulting fees from abbvie, almirall, amgen, avillion, bristol-myers squibb, boehringer ingelheim, celgene, eli lilly, janssen, leo pharma, novartis, pfizer, sanofi, and ucb pharma; abg: research/educational grants: allergan, eli lilly, incyte, janssen, leo pharma, novartis. current consulting/advisory board agreements/speakers bureau: abbvie, allergan, beiersdorf, bristol-myers squibb, celgene, dermira inc., dr. reddy’s laboratories, eli lilly, incyte, janssen, novartis, sienna pharma, sun pharma, ucb pharma, valeant; ab: consulting honoraria and clinical investigator: abbvie, aclaris, almirall, amgen, boehringer ingelheim, celgene, dermavant, dermira inc., eli lilly, genentech/roche, gsk, janssen, leo pharma, meiji, merck, novartis, pfizer, purdue pharma, regeneron, sandoz, sanofi genzyme, sienna pharma, sun pharma, ucb pharma, valeant, vidac. speaker’s fees: eli lilly, janssen, regeneron, sanofi genzyme; dt: research grants from celgene and novartis; honoraria for participation on ad boards, and speaker/consultancy fees for abbvie, almiral, amgen, boehringer ingelheim, celgene, dignity, dr. reddy’s laboratories, eli lilly, galapagos, gsk, janssen, leo pharma, morphosis, msd, novartis, pfizer, sandoz-hexal, regeneron/sanofi, ucb pharma; cl: speaker (honoraria) for abbvie, celgene, eli lilly, novartis. investigator for abbvie, actavis, amgen, boehringer ingelheim, celgene, coherus, corrona, dermira inc., eli lilly, galderma, glenmark, janssen, leo pharma, merck, novartis, novella, pfizer, sandoz, stiefel, wyeth. consulting and advisory board honoraria for abbvie, amgen, boehringer ingelheim, dermira inc., eli lilly, janssen, leo pharma, pfizer, sandoz, ucb pharma, vitae; yp: speaker (honoraria) from: abbvie, celgene, eli lilly, janssen, leo pharma, novartis, regeneron, sanofi genzyme. investigator (research grants) from abbvie, baxter, boehringer ingelheim, celgene, centocor/janssen, eli lilly, emd serono, gsk; leo pharma, medimmune, merck, novartis, pfizer, regeneron, takeda, ucb pharma; mb, ca: employees of ucb pharma; sk: employee of ucb pharma. consulting fees from avexis, colorado prevention center, diamedica, puretech, ucb pharma, zosano; kr: advisor and/or paid speaker for and/or participated in clinical trials sponsored by: abbvie, affibody, amgen, biogen, boehringer ingelheim, celgene, centocor, covagen, eli lilly, forward pharma, gsk, janssen-cilag, kyowa kirin, leo pharma, medac, merck sharp & dohme, novartis, ocean pharma, pfizer, regeneron, samsung biopepis, sanofi, takeda, ucb pharma, valeant, xenoport. acknowledgements the studies were funded by dermira inc. in collaboration with ucb pharma. ucb is the regulatory sponsor of certolizumab pegol in psoriasis. we thank the patients and their caregivers in addition to the investigators and their teams who contributed to this study. the authors acknowledge bartosz łukowski, msc, ucb pharma, brussels for publication coordination and amelia frizell-armitage, costello medical, cambridge, uk for medical writing and editorial assistance. all costs associated with development of this poster were funded by ucb pharma. conclusions • in patients randomized to czp 400 mg q2w, responder rates increased to week 48 and were higher than in the czp 200 mg q2w group. these rates then gradually decreased following dose reduction, indicating that continued treatment at 400 mg q2w may be needed to maintain optimal response. • long-term efficacy over three years was durable in patients who received czp 200 mg q2w. certolizumab pegol for treatment of plaque psoriasis: pooled three-year efficacy outcomes from two phase 3 trials (cimpasi-1 and cimpasi-2) k. gordon,1 r. b. warren,2 a. b. gottlieb,3 a. blauvelt,4 d. thaçi,5 c. leonardi,6 y. poulin,7 m. boehnlein,8 s. kavanagh,9 c. arendt,10 k. reich11,12 1medical college of wisconsin, milwaukee, wi, usa; 2dermatology centre, salford royal nhs foundation trust, manchester nihr biomedical research centre, the university of manchester, uk; 3department of dermatology, icahn school of medicine at mount sinai, new york, ny, usa; 4oregon medical research center, portland, or, usa; 5institute and comprehensive center for inflammation medicine, university hospital of lübeck, lübeck, germany; 6central dermatology and saint louis university school of medicine, st louis, mo, usa; 7centre de recherche dermatologique du québec métropolitain, québec, canada; 8ucb pharma, monheim, germany; 9ucb pharma, raleigh, nc, usa; 10ucb pharma, brussels, belgium; 11translational research in inflammatory skin diseases, institute for health services research in dermatology and nursing, university medical center hamburg-eppendorf, hamburg, germany; 12skinflammation® center, hamburg, germany czp 400 mg q2w (n=175) czp 200 mg q2w (n=186) all czp (n=361) age, years, mean (sd) 45.0 (12.9) 45.6 (13.2) 45.3 (13.0) male, n (%) 103 (58.9) 125 (67.2) 228 (63.2) bmi, kg/m2, mean (sd) 31.2 (7.9) 32.0 (7.8) 31.6 (7.8) pso disease duration, years, mean (sd) 18.5 (12.6) 17.7 (12.9) 18.1 (12.7) prior anti-tnf therapy,a n (%) 40 (22.9) 44 (23.7) 84 (23.3) bsa affected, %, mean (sd) 23.6 (14.3) 23.5 (14.9) 23.5 (14.6) pasi, mean (sd) 19.6 (7.3) 19.2 (7.2) 19.4 (7.3) pga score, n (%) 3 (moderate) 126 (72.0) 128 (68.8) 254 (70.4) 4 (severe) 49 (28.0) 58 (31.2) 107 (29.6) dlqi total score, mean (sd) 13.7 (6.9) 14.3 (7.4) 14.0 (7.1) apatients with exposure to ≥2 biologics (including anti-tnfs) for pso or psa prior to baseline, or primary failure to ≥1 (or secondary failure to ≥2) biologic therapies, were excluded from the study. bsa: body surface area; bmi: body mass index; czp: certolizumab pegol; dlqi: dermatology life quality index; pasi: psoriasis area severity index; pga: physician’s global assessment; pso: psoriasis; q2w: every 2 weeks; sd: standard deviation; tnf: tumor necrosis factor. table 1. demographics and baseline characteristics for all patients randomized to czp 400 mg q2w and czp 200 mg q2w week 0 20 40 60 80 100 0 24 48 72 96 120 144 r e sp o n d e r ra te ( % ) week 72.3 69.8 84.2 71.9 0 20 40 60 80 100 0 24 48 72 96 120 144 r e sp o n d e r ra te ( % ) open-label period with possible dose adjustmenta at week 48 all blinded patients received czp 200 mg q2w week 0 20 40 60 80 100 0 24 48 72 96 120 144 r e sp o n d e r ra te ( % ) 51.3 48.5 62.4 42.7 open-label period with possible dose adjustmenta at week 48 all blinded patients received czp 200 mg q2w at week 48 all blinded patients received czp 200 mg q2w open-label period with possible dose adjustmenta 46.7 56.1 45.7 41.6 aloading dose of czp 400 mg q2w at weeks 0, 2 and 4 or weeks 16, 18 and 20; bdepending on pasi response, any dose adjustments during the open-label period were either mandatory or at the discretion of the investigator. czp: certolizumab pegol; ld: loading dose; pasi: psoriasis area severity index; q2w: every two weeks. figure 1. pooled data from cimpasi-1 and cimpasi-2 figure 2. clinical response over three years of treatment (144 weeks) estimates of responder rate reflect the simple average response across the multiply imputed data sets, with missing data imputed using mcmc methodology. aall patients received czp 200 mg q2w at week 48; dose adjustments were permitted during the open-label phase based on pasi response and were either mandatory or at the discretion of the investigator; bpatients received loading dose of czp 400 mg at weeks 0, 2 and 4. czp: certolizumab pegol; dlqi 0/1: dermatology life quality index 0/1; mcmc: markov chain monte carlo; pasi 75/90: ≥75/90% improvement from baseline in psoriasis area and severity index; q2w: every 2 weeks. 0 16 32 40 48 144 maintenance periodinitial treatment period (double blind) open-label treatment <pasi 50 withdrawn screening 1:2:2 week lda czp 200 mg q2w (n=186) czp 200 mg q2w ≥pasi 50 ≥pasi 50 ≥pasi 50 96 open-label dose switchingb <pasi 50 withdrawn placebo q2w ≥pasi 75 responders <pasi 50 withdrawn <pasi 50 entered escape arm (czp 400 mg q2w) czp 400 mg q2w (n=175) lda ≥pasi 50 <pasi 75 randomization czp 400 mg q2w a) pasi 75 b) pasi 90 c) dlqi 0/1 czp 400 mg q2w czp 200 mg q2wa (n=175) dose reduction czp 200 mg q2wb czp 200 mg q2wa (n=186) dose continuation objective • to present pooled, three-year efficacy data from two phase 3 trials of certolizumab pegol in moderate to severe plaque psoriasis. acknowledgements: medical writing support was provided by prescott medical communications group (chicago, il) with financial support from ortho dermatologics | presented at the fall clinical dermatology conference • october 17-20, 2019 • las vegas, nv synopsis ◾ current formulations of tazarotene (gel/foam/cream) can cause irritation, which may limit their use1 ◾ a novel tazarotene 0.045% lotion formulation was developed utilizing polymeric emulsion technology, resulting in a more uniform distribution of the active ingredient and of the moisturizing excipients at the skin’s surface2 ◾ in a 12-week phase 2 study (nct02938494) in participants with moderate-to-severe acne, tazarotene 0.045% lotion was superior to vehicle for the coprimary endpoints (reduction in inflammatory and noninflammatory lesions and treatment success per evaluator global severity score grading)2 ◾ in addition, tazarotene 0.045% lotion was as effective as tazorac® (tazarotene 0.1% cream), but with fewer adverse events2 objective ◾ to examine the participant-reported outcomes from this phase 2 study of tazarotene 0.045% lotion methods ◾ participants aged 12 years and older were randomized (2:2:1:1) to receive double-blind treatment with tazarotene 0.045% lotion, tazarotene 0.1% cream, lotion vehicle, or cream vehicle ◾ in this study, cerave® hydrating cleanser and cerave® moisturizing lotion (l’oreal, ny) were provided as needed for optimal moisturization/cleaning of the skin ◾ participant-reported outcomes included: oily/shiny skin, acne-specific quality of life questionnaire (acne-qol), and subject self-assessment (ssa) ◾ data were analyzed descriptively in participants with available data at week 12; data for the cream and lotion vehicles were combined for this analysis results ◾ the intent-to-treat population included 210 participants ◾ at week 12, the percentage of participants who reported “no oily or shiny skin on face” was similar between tazarotene 0.045% lotion and tazarotene 0.1% cream and greater than combined vehicle (figure 1a) • among participants with any oily/shiny skin, the percentage who were “not bothered at all” was higher with lotion than with cream or vehicle (figure 1b) comparison of a novel tazarotene 0.045% lotion to tazarotene 0.1% cream: patient-reported outcomes from a phase 2 clinical trial zoe draelos, md1; fran cook-bolden, md2; lawrence green, md3; eric guenin, pharmd, phd, mph4; gina martin, mot5; radhakrishnan pillai, phd5 1dermatology consulting services, pllc, high point, nc; 2dept. of dermatology, mount sinai hospital center, new york, ny; 3dept. of dermatology, george washington university school of medicine, washington, dc; 4ortho dermatologics, bridgewater, nj; 5bausch health americas inc., petaluma, ca ◾ mean changes from baseline to week 12 in acne-qol domains generally indicated greater improvement with both tazarotene formulations (lotion and cream) than with vehicle in all 4 domains (figure 2) ◾ per ssa ratings, the percentage of participants who reported having 90-100% clear skin was similar between tazarotene lotion and cream and greater than vehicle (figure 3) figure 2. absolute mean change from baseline to week 12 in acne-qol (itt population) 0 2 4 6 12 10 8 self-perception role-emotional role-social acne symptoms 8.2 8.4 6.1 5.0 5.7 4.5 7.2 7.4 5.7 7.4 6.1 6.3 tazarotene 0.045% lotion (n=65) combined vehicle (n=61) a b so lu te m e a n c h a n g e f ro m b a se lin e tazarotene 0.1% cream (n=64) no imputation of missing values. acne-qol, acne-specific quality of life questionnaire; itt, intent-to-treat. figure 3. percentage of participants reporting 90-100% clear skin on the ssa (itt population) 0% 10% 20% 30% 40% 50% baseline n=69 n=72 n=69 week 12 n=65 n=64 n=61 38.5% 0% 0% 1.4% 35.9% 24.6% tazarotene 0.045% lotion combined vehicle p e rc e n ta g e o f p a rt ic ip a n ts tazarotene 0.1% cream no imputation of missing values. itt, intent-to-treat; ssa, subject self-assessment. ◾ conclusions ◾ consistent with the clinician-assessed primary endpoints, participant-reported skin oiliness, qol, and acne severity were improved with tazarotene 0.045% lotion versus vehicle ◾ taken together with the improved tolerability and similar efficacy of tazarotene 0.045% lotion versus tazarotene 0.1% cream,2 this novel lotion formulation may be a viable new treatment option that is as effective as cream with fewer adverse events references 1. zaenglein al, et al. j am acad dermatol. 2016;74(5):945-973. 2. tanghetti ea, et al. j drugs dermatol. 2019;18(6):542-548. author disclosures dr. zoe draelos received funding from ortho dermatologics to conduct the research presented in this poster. dr. fran cook-bolden has served as consultant, speaker, and/or investigator for galderma, leo pharma, almirall, cassiopea, ortho dermatologics, investigators encore, foamix, hovione, aclaris, and cutanea. dr. lawrence green has served as consultant, speaker, and/or investigator for almirall, cassiopea, ortho dermatologics, sol gel, and sun pharmaceuticals. dr. eric guenin is an employee of ortho dermatologics. ms. gina martin and dr. radhakrishnan pillai are employees of bausch health americas. figure 1. percentage of participants reporting “none/no oily skin on face” (a) and “not bothered at all” by oily skin in the past week (b) (itt population) a. none/no oily skin on face 0% 10% 20% 30% 40% baseline n=69 n=72 n=69 week 12 n=65 n=64 n=61 27.7% 7.2% 16.7% 8.7% 31.3% 18.0% tazarotene 0.045% lotion combined vehicle p e rc e n ta g e o f p a rt ic ip a n ts tazarotene 0.1% cream b. “not bothered at all” by oily skin in the past week 0% 10% 20% 30% 40% baseline n=65 n=61 n=64 week 12 n=48 n=44 n=50 31.3% 13.8% 8.2% 23.4% 25.0% 24.0% p e rc e n ta g e o f p a rt ic ip a n ts tazarotene 0.045% lotion combined vehicle tazarotene 0.1% cream no imputation of missing values. itt, intent-to-treat. skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 736 brief article successful treatment of refractory hailey-hailey disease with dupilumab: a case report nikita wong, ms1, andrew d. king, md, phd2, geoffrey a. potts, md2 1 wayne state university school of medicine, detroit, mi 2 department of dermatology, wayne state university, detroit, mi hailey-hailey disease (hhd) is an autosomal dominant blistering dermatosis with incomplete penetrance caused by an atp2c1 gene mutation.1 this gene mutation affects calcium homeostasis due to a defect in the secretory pathway ca2+/mn2+ atpase (spca1) located in the golgi apparatus (ga).1 this plays a key role in the assembly of desmosomes in the epidermis and thus is responsible for the defective cell adhesion. hhd presents clinically as recurrent vesicles and erosions in intertriginous areas such as the groin, axilla, neck, mammary folds, and perineum. notably, maceration and superinfections are often frequently seen and can complicate the clinical presentation. currently, there is no cure for hhd; however therapeutic options aim to minimize the exacerbating factors and manage patients’ symptoms. in this case report, we discuss a relentless case of hhd and the role of dupilumab, a biologic monoclonal antibody in the management of the disease. dupilumab was approved in 2017 by the us food and drug administration (fda) for the treatment of moderate to severe atopic dermatitis (ad), abstract introduction: hailey-hailey disease (hhd) is an autosomal dominant blistering dermatosis with incomplete penetrance caused by an atp2c1 gene mutation. currently, there is no cure for hhd; however therapeutic options aim to minimize the exacerbating factors and manage patients’ symptoms. case report: a 58-year-old male presented with a 10-year history of biopsy-proven hhd. he was seen consistently over the course of nine years with multiple flares a year consisting of pruritic and painful intertriginous plaques with involvement of the chest, upper arms, and back. his disease was recalcitrant to topicals, oral and topical antibiotics, phototherapy, and systemic corticosteroids. he was started on dupilumab and noticed significant improvement. conclusion: we present a case of hhd recalcitrant to various modalities of treatment. our description of rapid improvement with dupilumab suggests a role for th2 signaling in the pathophysiology of hhd. we propose that dupilumab works for hhd due to the significant skin barrier dysfunction, similar to atopic dermatitis, and consider whether inflammation plays an earlier role in the disease. although used for an off-label purpose, in this case, further studies should assess the clinical response and safety of patients with recalcitrant hhd treated with dupilumab. introduction https://www.zotero.org/google-docs/?up3xi9 https://www.zotero.org/google-docs/?c40idz skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 737 however, it has potential benefit for cutaneous disease beyond ad. a 58-year-old male presented with a 10-year history of biopsy-proven hhd. his mother presented in her 50s and his brother was also diagnosed with hhd. he was seen consistently over the course of nine years with multiple flares a year consisting of pruritic and painful intertriginous plaques with involvement of the chest, upper arms, and back. he was initiated on numerous topicals including betamethasone valerate 0.1% ointment, fluocinonide 0.05% ointment, triamcinolone 0.1% ointment, tacrolimus 0.1% ointment, pimecrolimus 1% cream, calcipotriol 0.005% cream, benzoyl peroxide 5% gel, clindamycin 1% solution, mupirocin 2% ointment, and zinc oxide paste. he had also tried in-clinic phototherapy for more than 4 months, home phototherapy for years, systemic treatment with multiple courses of oral antibiotics including doxycycline, minocycline, and cephalexin for flares, low dose naltrexone 3mg nightly for 5 months, acitretin up to 30mg daily over 9 months, glycopyrrolate 1mg twice daily, and multiple courses of prednisone. his clinical course was also complicated by perianal condyloma acuminata and cutaneous staphylococcus aureus infections. the most effective medications were topicals together with minocycline and prednisone tapers. however, minocycline was not tolerated due to cutaneous pigmentation in areas of hhd, and naltrexone was discontinued due to flaring of hhd with medication. the patient was started on dupilumab loaded with 600mg followed by 300mg every other week. by the first maintenance dose, he subjectively endorsed 80% clearance of his skin. in his own words, “my skin felt different within 24 hours of taking the first application and i started to notice my skin clearing within three days. i am pain-free for the first time in many, many years.” improvement remained on subsequent follow-up up to 10 months even with regular activity and sweating. hhd is caused by the loss of function of the atp2c1 gene which is responsible for the expression of ca2+/mn2+ atpase (spca1) necessary for ca2+ trafficking and regulation.2 insufficient levels of spca1 affect the morphology of the golgi apparatus (ga) resulting in defective intracellular signaling and post-transcriptional modifications.2 the overall result is acantholysis as maintaining ca2+ stores is vital for cell-cell adhesion. dysregulated signaling events from the endoplasmic reticulum (er) to the ga and beyond leads to chronic cellular stress. in turn, keratinocytes respond by producing pro-apoptotic states.3 the role of the immune system in hhd has been suggested with early success through treatment with calcineurin inhibitors such as cyclosporine as described by ormerod and berth-jones et al., and more recently topical tacrolimus suggesting the involvement of a t cell-dependent mechanism.4 notably, an analysis of untreated hhd lesions showed significant infiltration with t-lymphocytes that subsequently decreased after treatment with calcineurin inhibitors.5 this further implies that immunomodulators may have a role in the pathogenesis of hhd. our description of rapid improvement with dupilumab suggests a role for th2 signaling in the pathophysiology of hhd. alzahrani et al.’s case series suggest a role for il-4 and case report discussion https://www.zotero.org/google-docs/?yvhvls https://www.zotero.org/google-docs/?hxdtju https://www.zotero.org/google-docs/?vwimkb https://www.zotero.org/google-docs/?pgaach https://www.zotero.org/google-docs/?vsl0ym skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 738 figure 1. treatment of refractory hailey-hailey disease with dupilumab. erosive vesicles coalescing into thin plaques on chest, back, and groin at baseline (a-c). chest, back, and groin three months after treatment with dupilumab (d-f). il-13 in intracellular-calcium release via ccl26 and ccr3, an integral part of th2 cell differentiation.6 more recently, reports of significant improvement after treatment with dupilumab within a one-year follow-up period, further suggests that the inhibition of the il-4 and il-13 pathways may explain the effectiveness of dupilumab in treating hhd.7 alternatively, licata et al suggest that the skin barrier defect and associated acantholysis seen in hhd promotes local inflammation thus making il-4 a suitable target for dupilumab.8 we propose that dupilumab works for hhd due to the significant skin barrier dysfunction, similar to atopic dermatitis, and consider whether inflammation plays an earlier role in the disease. although used for an off-label purpose, in this case, further studies should assess the clinical response and safety of patients with recalcitrant hhd treated with dupilumab. additional patient cases being reported may help this orphan disease in terms of insurance coverage and encourage more patients to seek care. conclusion https://www.zotero.org/google-docs/?jtb1kh https://www.zotero.org/google-docs/?afwkzk https://www.zotero.org/google-docs/?wnlovt skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 739 acknowledgement: the patient in this case report has provided written informed consent for publication of his case details. conflict of interest disclosures: none funding: none corresponding author: geoffrey potts, md department of dermatology wayne state university 18100 oakwood blvd, suite 300 dearborn, mi 48124 email: gpotts@med.wayne.edu references: 1. dhitavat j, fairclough rj, hovnanian a, burge sm. calcium pumps and keratinocytes: lessons from darier’s disease and hailey-hailey disease. br j dermatol. 2004;150(5):821-828. doi:10.1111/j.13652133.2004.05904.x. 2. micaroni m, giacchetti g, plebani r, xiao gg, federici l. atp2c1 gene mutations in hailey–hailey disease and possible roles of spca1 isoforms in membrane trafficking. cell death dis. 2016;7(6):e2259-e2259. doi:10.1038/cddis.2016.147. 3. shull ge, miller ml, prasad v. secretory pathway stress responses as possible mechanisms of disease involving golgi ca2+ pump dysfunction. biofactors oxf engl. 2011;37(3):150-158. doi:10.1002/biof.141. 4. rabeni ej, cunningham nm. effective treatment of hailey-hailey disease with topical tacrolimus∗. j am acad dermatol. 2002;47(5):797-798. doi:10.1067/mjd.2002.126217. 5. tchernev g, cardoso j. familial benign chronic pemphigus (hailey-hailey disease): use of topical immunomodulators as a modern treatment option. rev médica chile. 2011;139:633-637. doi:10.4067/s003498872011000500011. 6. alzahrani n, grossman-kranseler j, swali r, et al. hailey–hailey disease treated with dupilumab: a case series. br j dermatol. 2021;185(3):680-682. doi:10.1111/bjd.20475. 7. alamon-reig f, serra-garcía l, boschamate x, riquelme-mc loughlin c, mascaró jm. dupilumab in hailey-hailey disease: a case series. j eur acad dermatol venereol jeadv. published online june 23, 2022. doi:10.1111/jdv.18350. 8. licata g, buononato d, calabrese g, et al. a case of hailey-hailey disease successfully treated with dupilumab. int j dermatol. published online june 29, 2022. doi:10.1111/ijd.16322. skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 189 in-depth reviews avoiding the hazards of ultraviolet light in the adolescent population alexander auchus1, robert t. brodell, md2, vinayak k. nahar, md, ms, phd, frsph2,3, kimberley h.m. ward, md2 1department of psychology, school of arts and sciences, university of pennsylvania, philadelphia, pa 2department of dermatology, school of medicine, university of mississippi medical center, jackson, ms 3department of preventive medicine, school of medicine, university of mississippi medical center, jackson, ms ultraviolet (uv) light in the uvb and uva ranges has been demonstrated to cause acute sunburn and chronic skin problems including wrinkles, brown spots (solar lentigines), sallowness, precancerous lesions including actinic keratoses, and skin cancer (basal cell carcinoma, squamous cell carcinoma, and melanoma).1-4 in fact, in 2009, uv-emitting tanning devices were classified as “carcinogenic to humans” (group 1) by the world health organization’s international agency for research on cancer.5 skin damage is increased with the strength of the uv light during mid-day (10am-2pm), cloudless days, higher altitudes, and the duration of exposure. the time to start protecting the skin from the hazards of uv is during childhood. many individuals receive half of their lifetime sun damage before age 18.6 sports and other outdoor recreational activities increase uv exposure. in addition, the widely held belief that tanned skin is beautiful motivates young people to use natural and artificial light to tan. many young people also feel a sense of invincibility that makes it difficult to convince them to protect themselves from ultraviolet radiation (uvr). while not everyone exposed to significant amounts of uv light will develop skin cancer, the lifetime risk of basal cell carcinoma in caucasian individuals is around 30%.7 most importantly, one severe sunburn in a lifetime has been shown to increase an individual’s risk of developing potentially life-threatening malignant melanoma.8,9 protection from the hazards of uv light remains the most important modifiable risk factor for skin cancer. this article will reinforce approaches to avoid the hazards of introduction exposure to uv light remains the major modifiable risk factor for skin cancer. studies have shown that adolescents do not adequately use sun protection and frequently engage in tanning behaviors. this article will reinforce approaches to avoid the hazards of uv light and provide tips and tricks that health care providers should emphasize to their adolescent patients. abstract skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 190 tanning and provide tips and tricks that health care providers should provide to their adolescent patients. avoid artificial uv exposure unfortunately, “even one indoor tanning session can increase users' risk of developing melanoma by 20 percent, squamous cell carcinoma by 67 percent and basal cell carcinoma by 29 percent” according to the american academy of dermatology. thus, our patients should be encouraged to avoid all artificial uv tanning devices. advocacy efforts should promote state laws that prohibit tanning of youth under age 18. a number of states already have such laws (figure 1). protection from outdoor uv light adolescents should avoid the peak mid-day sun and seek shade structures when available. in addition, they should shield their skin from uvr using the following evidence-based techniques. hats the most convenient way to protect the face and neck from uvr is to wear a widebrimmed hat. unfortunately, the most commonly worn hat is a baseball cap. these flat or peak capped hats provide minimal uvr protection for the ears, cheek, chin, and back of neck as seen in table 1. while large brimmed hats (>7.5cm) are recommended for all individuals, these hats still provide less than a sun protection factor (spf) 10 to the nose, cheek, chin, and back of neck; therefore, sunscreen should be worn with the hat.10 visors used over hard hats by workers are also adaptable to various helmets used in sports (see figure 2). protective clothing the use of protective clothing is as important as using a hat in shielding areas of the body from direct uv exposure.11 bikinis and men’s brief style swimsuits expose more skin to the sun than one-piece women’s suits and men’s jammer styles that cover the thighs. wearing light-colored, long-sleeved shirts is also recommended because individuals who wear protective clothing have been shown to suffer fewer sunburns when compared to individuals who apply sunscreen alone.12 adolescents should be encouraged to wear uvr blocking clothing; denim, cotton, nylon, and polyester are some of the most effective uva and uvb protective fabrics currently available on the market.11 protective clothing should be worn even in the water at the pool or beach, but it should be noted that cotton fabric transmits uv light to underlying skin much more effectively when wet.13 physicians should also recommend clothing labeled with ultraviolet protection factors (upfs) as an easy way to ensure that the chosen clothing will be effective uvr blockers. clothing with a upf of 30, for example, protects the skin from all but 1/30th of uv radiation. sunscreens sunscreen should also be used in conjunction with protective clothing in order uv blocking clothing is an important component to avoiding the hazards of uv light exposure problems + practical solutions a baseball (peaked) cap does not provide significant uv protection to the ears, cheeks, chin, and back of the neck. skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 191 figure 1. map of state laws prohibiting minors from using tanning devices figure 2. type of uv protective head gear classified by brim. skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 192 to more completely protect the skin from the hazards of uvr. as an example of the efficacy of this multifaceted recommendation, the famous australian slip! slap! slop! (slip on a shirt, slap on a hat, and slop on sunscreen) campaign resulted in significant positive changes in attitudes toward sun tanning in australia resulting in decreased rates of melanoma.14 a broad-spectrum, water-resistant sunscreen with an spf of 30 or greater should be recommended for its ability to protect the skin from sunburn, premature photoaging, and precancerous sun damage.15 an spf of 30 implies that individuals can stay in the sun for 30 times longer with the product than without the product to receive the same amount of uvr. some products are more substantive, that is, they resist washing off when sweating or in the water. these formulations are termed “water-resistant” since the fda will no longer allow labeling as “water proof”.16 it is important to note that at least one ounce of sunscreen is needed to effectively cover the entire body of an average sized adult and that sunscreen should be reapplied about every two hours or more often if sweating or in water.17 patients should also be advised to take the time necessary to distribute sunscreen evenly across the entirety of the exposed skin, as hasty sunscreen application results in uneven protection.18 in order to address this issue, some resorts have installed sunscreen booths that spray sunscreen evenly over the entire body with minimal effort.19 in general, because chemical agents have reduced photostability,20 chemical sunscreens may necessitate more frequent reapplication. conversely, physical agents are desirable because they provide broadspectrum uv protection and are completely photostable.20 however, physical agents often leave a visible white residue on the skin. they also remain on the skin longer than many chemical agents and thus may be more difficult to remove. a wide range of sunscreens products with chemical and physical sunscreen agents are available in the u.s. market. these sunscreen agents offer certain advantages and disadvantages (see table 2). considering the range of cream, lotion, gel, spray, stick, oil, and powdered products that are available, we recommend that patients choose the sunscreen they like best so long as it has an spf of 30 or greater. table 1. summary of sun-protection factors at various sites on the head and neck provided by different types of hats. typical sun-protection factor style of hat forehead nose cheek chin back of neck small brim (< 2.5 cm) 15 1.5 1 1 1 medium brim (2.5 7.5 cm) >20 3 2 1 2 large brim (> 7.5 cm) >20 7 3 1.2 5 peaked cap >20 5 1.5 1 1 a broad spectrum (uva and uvb) blocking sunscreen with an spf greater than 30 should be recommended for routine use outdoors skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 193 people are more likely to use the product that they like; the benefits of routinely using a favorite product overshadow the potential benefits of using one recommended product. for now, it is abundantly clear that sunscreens as part of a multi-modal effort can reduce actinic keratoses, skin cancers, wrinkles, and solar lentigines. responding to challenging patient questions some patients resist wearing sunscreen for very specific reasons. health care providers should be prepared to respond to the following issues often raised by patients: 1) “it leaves a white residue” white residue results from the physical sunscreen agents titanium dioxide and zinc oxide. even micronized formulations can be difficult to rub into the skin and often leave a white powdery residue. despite this drawback, they provide a broad-spectrum, high spf and are often quite substantive. in other words, they do not wash off easily when swimming or sweating. although not as substantive, chemical sunscreens are alternatives that do not usually leave white residue. 2) “it contains dangerous nanoparticles.” micronized physical sunscreens do contain nanoparticles. there is ongoing research regarding potential side effects of these products, but studies to date demonstrate minimal systemic absorption.23,24 the fda would not allow these products to remain on the market if there was evidence of significant toxicity. additionally, chemical sunscreen agents do not contain nanoparticles and can be used as alternatives to nanoparticle physical sunscreens if desired. 3) “it stings my eyes.” chemical sunscreens are more likely to cause stinging of the eyes when sweating causes them to flow into the eyes from the forehead.25 physical sunscreens generally do not cause this side effect and may be appropriate for athletes who complain of this problem. 4) “it causes cancer.” there is evidence that urocanic acid, a sunscreen agent previously used in europe, may be carcinogenic.26 however, this agent was never used in sunscreen formulations in the u.s.a. in fact, none of the currently fda approved sunscreen agents are carcinogenic. there is also no evidence that sunscreen agents are harming humans in the concentrations to which we are exposed.27 a second mechanism has also been postulated whereby sunscreen could “cause cancer:” wearing uvb blocking sunscreen alone without uva protection could result in individuals remaining in the sun for longer periods of time, thus accumulating more significant uva damage. uva penetrates the skin more deeply and may be particularly associated with solar elastosis and malignant melanoma. however, physicians recommend using a broad-spectrum sunscreen that protects against both uva and uvb rays in patients should choose the sunscreen they like among available products with spf 30 or greater physicians should be prepared to answer the specific reasons patients present to explain their lack of adherence to recommended sunscreen use skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 194 table 2. “sunscreen agents: range covered, advantages, and disadvantages” chemical sunscreen agent range covered21 uva1: 340-400 nm uva2: 320-340 nm uvb: 290-320 nm advantages disadvantages aminobenzoic acid (paba) uvb long lasting (penetrates horny layer).22 can stain clothing can cause allergic or photoallergic dermatitis.22 avobenzone uva1 can cause allergic and photoallergic reactions.22 cinoxate uvb rarely causes photoallergic contact dermatitis.22 dioxybenzone uvb, uva2 may cause allergic contact dermatitis.22 ecamsule (mexoryl sx) uva2 can cause allergic and photoallergic reactions.22 ensulizole (phenylbenzimiazole sulfonic acid) uvb can cause allergic and photoallergic reactions.22 homosalate uvb can cause photoallergic reactions.22 meradimate (menthyl anthranilate) uva2 may cause irritant, allergic, and photoallergic reactions.22 octocrylene uvb can cause allergic and photoallergic reactions.22 octinoxate (octyl methoxycinnamate) uvb poor water solubility (waterresistant).22 commonly causes allergic and photoallergic reactions.22 possible cross-reactivity with flavorings and fragrances.22 octisalate (octyl salicylate) uvb can cause all 4 types of contact dermatitis.22 oxybenzone uvb, uva2 commonly causes irritant, allergic, and photoallergic dermatitis.22 may induce photo contact urticaria, contact urticaria, and anaphylaxis.22 nonsteroidal antiinflammatory drugs may cross-react.22 skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 195 padimate o uvb can cause photoallergic contact dermatitis.22 sulisobenzone uvb, uva2 can cause all 4 types of contact dermatitis.22 may cause urticarial reactions.22 trolamine salicylate uvb may cause allergic reactions.22 physical sunscreen agent titanium dioxide uvb, uva2 difficult to rub in. zinc oxide uvb, uva2, uva1 offers comprehensive uv protection. difficult to rub in. micronized zinc oxide uvb, uva2, uva1 offers comprehensive uv protection. easier to rub in. micronized titanium dioxide uvb, uva2 easier to rub in. conjunction with hats, protective clothing, and seeking shade when possible. thus, this fear is tenuous at best. 5) “it hurts the environment” recent evidence suggests that the chemical sunscreen ingredient oxybenzone/benzophenone-3 and related sunscreens may have a toxicological impact on the environment. the facts are: 1) minute amounts of oxybenzone from sunscreen use and manufacture is detectable in oceans, swimming pools, and lakes; 2) oxybenzone can destroy coral by bleaching; and 3) 4-methylbenzylidene camphor, oxybenzone, octocrylene and octinoxate have been identified in fish.27 with regard to coral, studies have shown damage to coral in the immediate vicinity of beaches where sunscreens are worn by thousands of swimmers.27 however, only about 10% of global reefs and up to 40% of coastal reefs are at risk for coral bleaching.28 with this in mind, and recognizing that no perfect sunscreen exists, banning the use of these products is premature. if a more significant threat to the coral reef ecosystem is proven, this could be reconsidered. 6) “i am allergic to sunscreen.” chemical sunscreens are generally less well tolerated when compared to physical agents. many chemical agents produce allergic or photoallergic reactions including: aminobenzoic acid (paba), avobenzone, dioxybenzone, ecamsule (mexoryl sx), ensulizole (phenylbenzimiazole sulfonic acid), homosalate, meradimate (menthyl anthranilate), octocrylene, octinoxate (octyl methoxycinnamate), octisalate (octyl salicylate), oxybenzone, padimate o, sulisobenzone, and trolamine salicylate.22 for patients experiencing allergic reactions skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 196 to a sunscreen, they can try sunscreens containing different chemicals or use physical agents. of course, it is possible for individuals to be allergic to preservatives or fragrances used in any sunscreen product. patch testing can define the specific ingredients causing allergic contact dermatitis and a simple switch to a physical sunscreen should eliminate this problem.22 7) “i will get vitamin d deficiency and develop weak bones.” for individuals worried about their vitamin d levels, it is recommended that they ingest 2000 international units (iu) of vitamin d daily from food, dietary supplements, or both. damaging the skin with uv is not required to maintain adequate vitamin d levels. sunless methods of tanning while some experts suggest that sunless tanning products should be avoided because they glorify tanning, we favor this safe alternative to achieving the “tan look” versus uv damage to the skin. of course, adolescents should be warned that sunless tanning products provide negligible sun protection and can even increase one’s susceptibility to uv-induced free radicals.29 thus, it is imperative that sunscreen and other sun protective behaviors be employed when using sunless tanning products. there are two categories of topical sunless tanning products. first, the sugars dihydroxyacetone and erythrulose produce a “maillard reaction” in the outer layers of the stratum corneum and epidermis, which results in a tan appearance.30 these products are topically applied daily until the desired color is achieved and then are reapplied as needed (usually weekly). the second category, bronzing products, consists of water-soluble pigments that produce a temporary tanned appearance until they are washed off. these pigments are commonly used in makeup and tinted lotions. table 3 describes the various sunless tanning agents available in the u.s. market. motivation despite proper warning and instruction, many adolescents will choose not to engage in sun protective behaviors in favor of “beautiful,” tanned skin. one approach is to warn adolescents that uv causes dna table 3. sunless tanning agents: advantages and disadvantages tanning agent advantages disadvantages dha (dihydroxyacetone) produces a tan color that lasts about a week.31 can induce uv-generated free radicals in the skin.29 can produce a streaky or blotchy color. erythrulose when used with dha, the color produced reportedly lasts longer and has a more natural tone.32 color produced may be tinted yellow or red.29 produces a more temporary color than dha.32 can produce a streaky or blotchy color. water soluble pigments allow for more even application. last about 24 hours or until washed off.30 sunless tanning products represent a safe way to “look tan.” skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 197 damage and thus predisposes one to a higher risk of skin cancer.33 however, studies suggest that adolescents do not believe or do not care that they will develop skin cancer. instead of this approach, we favor warning adolescents about the deleterious effects of uvr on the appearance of one’s skin.34 adolescents must be warned that while not everyone with sun-damaged skin will get skin cancer, 100% will have sallowness, wrinkles, loss of elasticity, and brown spots. one study demonstrated a significant increase in sunscreen use among a group of adolescents who were shown a video explaining the appearance-based consequences of uvr. the group shown a similar video describing the health-based consequences of uvr did not see an increase in sunscreen use.35 in another controlled study, college-aged females tanned less often after receiving a workbook describing the damaging effects of indoor tanning on the skin’s appearance.36 similarly, adolescents had intentions to use both sunscreen and other forms of sun when shown pictures of unsightly skin discoloration on areas of the face and neck that resulted from a lack of sun protection.37 finally, the sunfacetm mobile application edits facial images to highlight the potential effects of photoaging. a 2017 pilot study demonstrated that 63% of participants agreed that the edited picture “motivated them to avoid using a tanning bed” and 62% agreed “to increase use of sun protection”.38 thus, appearance-based fear tactics are effective in improving adherence of sun protective behaviors in young people.34,35 even when adolescents adopt sun protective behaviors, it has been shown that they do not maintain their efforts over time. text-message reminders to wear sunscreen, long sleeves, and hats may serve to encourage adolescents to protect themselves from the sun. for example, one 6-week study of 70 participants showed that those in the experimental group who received daily text-message reminders to wear sunscreen had significantly higher rates of adherence compared to those in the control group.39 in summary, it is abundantly clear that sunscreens should play a part in a multimodal effort to reduce actinic keratoses, skin cancers, wrinkles and solar lentigines. adolescents and their parents are critical targets for education efforts to reduce skin damage from uvr. physicians play an integral role in this process by promoting healthy habits and stressing that there is no safe amount of uv tanning. conflict of interest disclosures: robert brodell, m.d. discloses the following potential conflicts of interest: multicenter clinical trials: galderma laboratories, l.p. – principal investigator; novartis principal investigator; and, glaxo smith kline – principal investigator; editorial boards: american medical student research journal; practice update dermatology; practical dermatology; practical dermatology; journal of the mississippi state medical society; skin: the journal of cutaneous medicine and, journal of the american academy of dermatology. there are no conflicts of interest related to employment, stock ownership, expert testimony, grants, patents filed, received, pending, or in preparation, or royalties. alexander auchus, vinayak k. nahar, and kimberly ward have no conflicts of interest funding: none conclusion the effects of uv on appearance may motivate our patients more effectively than fear of developing cancer skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 198 corresponding author: vinayak k. nahar, md, ms, phd, frsph department of dermatology university of mississippi medical center 2500 north state street – l216 jackson, ms 39216 usa phone: 601-815-5876 email: naharvinayak@gmail.com references: 1. fisher, g. j., wang, z., datta, s. c., varani, j., kang, s., & voorhees, j. j. 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(2001). slip! slop! slap! and sunsmart, 1980-2000: skin cancer control and 20 years of populationbased campaigning. health education & behavior,28(3), 290-305. doi:10.1177/109019810102800304 15. hughes, m., williams, g., baker, p., & green, a. (2013). sunscreen and prevention of skin aging. annals of internal medicine, 158(11). doi:10.7326/0003-4819-158-11-20130604000001 16. center for drug evaluation and research. (n.d.). understanding over-the-counter medicines questions and answers: fda announces new requirements for over-the-counter (otc) sunscreen products marketed in the u.s. retrieved from https://www.fda.gov/drugs/resourcesforyou/consu mers/buyingusingmedicinesafely/understandingo ver-the-countermedicines/ucm258468.htm 17. center for drug evaluation and research. (n.d.). consumer updates sunscreen: how to help protect your skin from the sun. retrieved from https://www.fda.gov/forconsumers/consumerup dates/ucm239463.htm 18. norris, j. f. 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(2014). adverse reactions to sunscreen agents: epidemiology, responsible irritants and allergens, clinical characteristics, and management. dermatitis, 25(6), 289-326. doi:10.1097/der.0000000000000079 23. monteiro-riviere, n. a., wiench, k., landsiedel, r., schulte, s., inman, a. o., & riviere, j. e. (2011). safety evaluation of sunscreen formulations containing titanium dioxide and zinc oxide nanoparticles in uvb sunburned skin: an in vitro and in vivo study. toxicological sciences,123(1), 264-280. doi:10.1093/toxsci/kfr148 24. cross, s. e., innes, b., roberts, m. s., tsuzuki, t., robertson, t. a., & mccormick, p. (2007). human skin penetration of sunscreen nanoparticles: in-vitro assessment of a novel micronized zinc oxide formulation. skin pharmacology and physiology, 20(3), 148-154. doi:10.1159/000098701 25. foley, p., nixon, r., marks, r., frowen, k., & thompson, s. (1993). the frequency of reactions to sunscreens: results of a longitudinal population-based study on the regular use of sunscreens in australia. british journal of dermatology, 128(5), 512-518. doi:10.1111/j.1365-2133.1993.tb00227.x 26. final report on the safety assessment of urocanic acid. (1995). journal of the american college of toxicology, 14(5), 386-423. doi:10.3109/10915819509083599 27 schneider, l. s., & lim, w. h. (2018). review of environmental effects of oxybenzone and other sunscreen active ingredients. journal of the american academy of dermatology 28. pdf. (n.d.). south florida, hawaii, u.s. virgin islands, american samoa: national park service u.s. department of the interior. 29. jung, k., seifert, m., herrling, t., & fuchs, j. (2008). uv-generated free radicals (fr) in skin: their prevention by sunscreens and their induction by self-tanning agents. spectrochimica acta part a: molecular and biomolecular spectroscopy, 69(5), 1423-1428. doi:10.1016/j.saa.2007.09.029 30. o’leary, r. e., diehl, j., & levins, p. c. (2014). update on tanning: more risks, fewer benefits. journal of the american academy of dermatology, 70(3), 562-568. doi:10.1016/j.jaad.2013.11.004 31. pagoto, s. l., schneider, k. l., oleski, j., bodenlos, j. s., merriam, p., & ma, y. (2009). design and methods for a cluster randomized trial of the sunless study: a skin cancer prevention intervention promoting sunless tanning among beach visitors. bmc public health, 9(1). doi:10.1186/1471-2458-9-50 32. garone, m., howard, j., & fabrikant, j. (2015). a review of common tanning methods. the journal of clinical aesthetic dermatology, 8(21), 43-47. 33. barsh, g., & attardi, l. (n.d.). a healthy tan? the new england journal of medicine., 356(21), 2208–2210. doi:10.1056/nejmcibr071775 34. mahler, h. i., kulik, j. a., gerrard, m., & gibbons, f. x. (2007). long-term effects of appearancebased interventions on sun protection behaviors. health psychology, 26(3), 350-360. doi:10.1037/0278-6133.26.3.350 35. tuong, w., & armstrong, a. w. (2014). effect of appearance-based education compared with health-based education on sunscreen use and knowledge: a randomized controlled trial. journal of the american academy of dermatology, 70(4), 665-669. doi:10.1016/j.jaad.2013.12.007 36. hillhouse, j., & turrisi, r. (2002). examination of the efficacy of an appearance-focused intervention to reduce uv exposure. journal of behavioral medicine., 25(4), 395–409. doi:10.1023/a:1015870516460 37. mahler, h. i., kulik, j. a., gibbons, f. x., gerrard, m., & harrell, j. (2003). effects of appearancebased intervention on sun protection intentions and self-reported behaviors. health psychology,22(2), 199-209. doi:10.1037//02786133.22.2.199 38. brinker, t. j., faria, b. l., gatzka, m., faria, o. m., heppt, m. v., kirchberger, m. c., . . . bernardes-souza, b. (2018). a skin cancer prevention photoageing intervention for secondary schools in brazil delivered by medical students: protocol for a randomised controlled trial. bmj open, 8(3). doi:10.1136/bmjopen2017-018299 39. armstrong, a., watson, a., makredes, m., frangos, j., kimball, a., & kvedar, j. (n.d.). textmessage reminders to improve sunscreen use. archives of dermatology., 145(11). doi:10.1001/archdermatol.2009.269 microsoft word september 2020 bar 866 proof.docx skin september 2020 volume 4 issue 5 copyright 2020 the national society for cutaneous medicine 449 brief articles blistering rash over broken ribs kathleen r. graham, md1, bethany r. rohr, md2, victor j. marks, md3 1department of internal medicine, summa health system, oh 2department of dermatology, university hospitals, oh 3department of dermatology, geisinger health system, danville, pa fracture blisters are the result of skin separation with fluid collection at the dermal epidermal junction (dej). these bullae are an uncommon complication of fractures. following a traumatic injury, patients should be monitored for the formation of fracture blisters. bullae usually develop within 24-48 hours after injury, but have been documented as early as 6 hours.1 prompt recognition and identification can improve management plans. we present a case of a 55-year-old man with fracture blisters found in a previously undocumented location. a 55-year-old man presented to the emergency department one day after a fall while intoxicated. after chest x-ray was performed, he was diagnosed with rightsided 5th and 6th rib fractures, a pulmonary contusion, and a pneumothorax secondary to the impact (figure 1). dermatology was consulted for a blistering rash overlying the site of the rib fractures. the patient reported that the blisters were not initially present at the time of injury but were noticed the next morning at the time of this encounter. he denied associated pain, pruritus, or a personal or family history of blistering diseases. exam revealed a six-centimeter pink patch with multiple overlying clear-toyellow serous fluid filled bullae and an erosion at the site of a ruptured bulla on the right lateral chest wall overlying the rib fractures (figure 2). differential included fracture blisters, varicella zoster virus, herpes simplex virus, bullous pemphigoid, bullous arthropod. routine bacterial culture and viral polymerase chain reaction for varicella-zoster virus and herpes simplex virus types 1 and 2 from the base of a ruptured bulla were negative, and the patient was diagnosed with fracture blisters. the abstract fracture blisters are painless fluid-filled bullae most commonly located over fractures of the distal tibia and humerus. they are diagnosed clinically. invasive procedures and treatments increase the risk of wound infection and should be avoided. while there is no consensus on management, evidence supports leaving the blisters intact and treating erosions with topical barrier ointments or topical antibiotics. we present a rare case of a 55-year-old man with fracture blisters located superficial to trauma-induced rib fractures that were successfully treated with topical mupirocin. introduction case presentation skin september 2020 volume 4 issue 5 copyright 2020 the national society for cutaneous medicine 450 patient quickly improved with topical mupirocin ointment and gauze dressings applied to the bullae and erosions. at onemonth follow-up, the patient noted complete resolution of the bullae without subsequent rash. figure 1. ap chest x-ray during expiration. the top three arrows point to the pneumothorax, and the right bottom arrow points to the rib fractures. fracture blisters are subepidermal bullae that form superficially to an underlying fracture.1,2 traumatic injury creates shearing forces, hypoxia, and increased interstitial pressure that contribute to epidermal-dermal separation and fluid collection.2-6 the epidermis and dermis differ in biomechanical properties, which allows for shearing forces to cause separation at the dej.1,3 the more severe the mechanism of injury the greater the risk for fracture blister formation. the patient in our case experienced a fall while intoxicated and was unable to provide more details regarding the mechanism of injury. the presence of his pneumothorax and pulmonary contusion suggests a high-energy trauma, which placed him at higher risk for developing fracture blisters. certain comorbidities that impair skin integrity can further contribute to fracture blister formationincluding smoking, alcoholism, and diabetes mellitus.1,4 trauma patients often have multiple comorbidities placing this population at a higher risk for fracture blister development.7 figure 2. image of the right lateral chest wall overlying the 5th and 6th ribs shows a six-centimeter pink patch with multiple clear-to-yellow serous fluid filled bullae and an erosion. fracture blisters are a clinical diagnosis and identification can prevent unnecessary biopsies or other interventions. the blisters are classically painless. blood-filled blisters are flaccid, while serous-filled blisters are tense.1 blister formation is typically noticed within 24-48 hours of injury, but has been recorded at as early as 6 hours and as late as 3 weeks after injury.1,2 typical blister locations include the distal tibia and humerus.1,2,5,8 the patient in our case developed fracture blisters over fractured discussion skin september 2020 volume 4 issue 5 copyright 2020 the national society for cutaneous medicine 451 ribs, which is a location that has not been previously documented. prevention strategies include elevation of the affected extremity and early surgical fixation before presence of blisters.1,5 there is no consensus on the treatment for fracture blisters.4 current evidence recommends avoiding surgery when fracture blisters are present. if the patient requires an emergent operation, then incision directly through blood-filled blisters should be avoided as it is associated with higher morbidity.3 there is conflicting evidence on whether to leave the blisters intact or de-roof them.1,4 fracture blister fluid is sterile, but when blisters are de-roofed, bacterial colonization occurs rapidly and can be a source of morbidity.1 the use of topical barrier ointment, silver sulfadiazine, or a topical antibiotic on spontaneously ruptured blister beds is recommended.3,6 a recent case study described the addition of an oral antibiotic with blister rupture to prevent complications.9 on average, serous filled blisters re-epithelialize in 12 days and blood filled blisters in 16 days.3 fracture blisters are an uncommon complication of trauma-induced fracture.1,8 while typically found at the distal tibia or humerus, fracture blisters can be found at other locations. clinicians should maintain a high index of suspicion for fracture blisters when evaluating trauma patients as early identification can improve patient care by providing proper management and preventing invasive procedures. conflict of interest disclosures: none funding: none corresponding author: kathleen r graham, md department of internal medicine summa health system 55 arch street, ste 1b akron, oh 44304 phone: 330-714-3978 email: grahamkat@summahealth.org references: 1. refs varela c, vaughan tk, carr j, et al. fracture blisters: clinical and pathologic aspects. j of orthopedic trauma. 1993;7(5):417– 27. 2. wallace gf, sullivan j. fracture blisters. clin podiatric med surg. 1995;12(4):801–12. 3. giordano cp, koval kj, zuckerman jd, desai p. fracture blisters. clin orthop relat res. 1994;(307):214-221. 4. strauss e, petrucelli g, bong m, koval k, egol k. blisters associated with lower extremity fracture: results of a prospective treatment protocol. j of orthopedic trauma. 2006 oct;20(9):618–622. 5. ballo f, maroon m, millon sj. fracture blisters. j am acad dermatol. 1994;30:1033-1034. 6. finklea lb, becker le. hemorrhagic and serousfilled vesicles and bullae. fracture blisters. jama dermatol. 2013;149:751-756. 7. tan cp, ng a, civil i. co-morbidities in trauma patients: common and significant. n z med j. 2004;117:u1044. 8. uebbing cm, walsh m, miller jb, abraham m, arnold c. fracture blisters. west j emerg med. 2011;12(1):131-133. 9. halawi mj. fracture blisters after primary total knee arthroplasty. am j orthop. 2015;44(8):e291-e293. conclusion genomic profiling of lentigo maligna within an interim registry analysis greg stevens dmsc, pa-c1, burkhard jansen, md1, terry arnold, mba, pa-c1, james rock, ms1, jennifer wood, dmsc, pa-c1, mark hyde, phd, pa-c1, loren clarke, md1 1. dermtech, 11099 north torrey pines road, suite 150 la jolla, ca 92037, usa abstract introduction and objective methods between april 2021 and march 2022, approximately 8000 lesions were entered into a nationwide registry from 63 unique sites. sites were encouraged to enter all results, including corresponding histopathology. histopathologic diagnoses were categorized first into melanoma and nonmelanoma. among melanomas, the number of lm subtype was determined, including the number of lmm subtype. among non-melanomas, the number of sdn/ajmh was determined. all uncertain cases were reviewed by a boardcertified dermatopathologist. furthermore, correlation between genomic markers present and lm/lmm/ajmh diagnoses was calculated. the gene expression test is designed to rule out melanoma by analyzing noninvasively collected skin cells from pigmented lesions for genomic atypia (linc00518, prame, and/or tert). the results of the test are designed to guide biopsy decisions on clinically suspicious pigmented lesions that violate one or more of the abcde criteria. this approach improves pigmented lesion management beyond visual inspection with a negative predictive value of ≥99% and a sensitivity of 91-97%, and by enriching melanoma among biopsied lesions almost 5-fold.1-3 the real-world performance of the test and its impact on clinical practice has been addressed in a previously completed 2020 patient registry, and summarized in 2 peer reviewed publications.3,4 1. gerami p, yao z, polsky d, et al. development and validation of a noninvasive 2-gene molecular assay for cutaneous melanoma. j am acad dermatol. 2017;76(1):114-120.e2. 2. jackson sr, jansen b, yao z, ferris lk. risk stratification of severely dysplastic nevi by non-invasively obtained gene expression and mutation analyses. skin the journal of cutaneous medicine. 2020;4(2):105-110. 3. brouha b, ferris lk, skelsey, mk, et al. genomic atypia to enrich melanoma positivity in biopsied lesions: gene expression and pathology findings from a large u.s. registry study. skin. 2021;5(1),13–18. 4. brouha b, ferris lk, skelsey mk, et al. real-world utility of a non-invasive gene expression test to rule out primary cutaneous melanoma: a large us registry study. j drugs dermatol. 2020;19(3):257-262. 5. skelsey mk, brouha b, rock j, et al. non-invasive detection of genomic atypia increases real-world npv and ppv of the melanoma diagnostic pathway and reduces biopsy burden. skin. 2021;5(5), 512–523. references results table 1. figure 1 of the approximately 8000 lesions entered into the registry from april 2021 to march 2022, 1021 (12.8%) were positive for at least one genomic biomarker. eighteen of these lesions did not have histopathologic diagnoses available. of the 1003 complete cases, 134 (13.4%) were diagnosed as melanoma; 46 (34.3%) were lm subtype, with 7 of those being lmm. of the non-melanoma lesions, an additional 7 (0.8%) were classified as ajmh. these results are depicted in the figure. funding/disclaimer: all study sites were reimbursed by dermtech for the collection of data; the authors are employed by dermtech. conclusion this interim registry analysis demonstrates use of the dmt in assessing atypical pigmented macules and patches on chronically sunexposed areas. while the original validation studies included the lm subtype, this data represents a larger real-world set. over 1/3 of the melanomas reported were classified as lm subtype. linc has a higher correlation with lm and was present in all 7 invasive tumors. while ajmh is considered borderline, it may be helpful in the clinical context to group ajmh lesions with lm due to similarities in treatment. lm = lentigo maligna lmm = lentigo maligna melanoma ajmh = atypical junctional melanocytic hyperplasia scan qr code for additional peer-reviewed publications regarding this genomic test background: pigmented lesion analysis remains a challenging aspect of dermatology. the dermtech melanoma test (‘the test’) is a non-invasive gene-expression test designed to rule-out melanoma. it consists of the pigmented lesion assay, which detects rna products of long intergenic non-coding rna 00518 (linc00518) and preferentially expressed antigen in melanoma (prame), and an add-on assay for dna promoter mutations in telomerase reverse transcriptase (tert). in previous studies, the test was found to have a negative predictive value ≥99%. this registry study examines the genomic patterns of the lentigo maligna (lm) subtype of melanoma. methods: between april 2021 and march 2022, multiple geographically diverse sites throughout the us submitted data to a registry to assess real-world use of the test. approximately 8,000 clinically atypical lesions were tested. after receiving the test result, providers followed their clinical judgement for biopsy decision. histopathologic diagnoses for biopsied lesions were correlated with test results and all melanomas were sorted into lm subtype vs non-lm subtype. in addition, lesions that were noted to be on sun exposed skin and/or noted to have solar elastosis and called atypical melanocytic hyperplasia were evaluated. results: at the 1-year mark of the registry, there were roughly 8000 unique entries. of those, 1003 expressed one or more genomic markers from the dmt and had records available, and 134 (13.2%) were found to be melanoma or melanoma insitu. more than a third (n=46, 34.3%) of the melanomas were of the lentigo maligna sub-type, with 7 of those being lentigo maligna melanoma (lmm). seven additional lesions were called atypical junctional melanocytic hyperplasia (ajmh) on sun-damaged skin. this group of 53 lm, lmm, and ajmh lesions were all evaluated for correlations to the dmt markers. linc was the most commonly expressed genomic marker (n=45, 84.9%), with prame (n=36, 67.9%) and tert (n=24, 45.3%) following. most invasive tumors (lmm) expressed all three markers (n=4) and all 7 expressed linc. conclusions: while the original validation study included the lm subtype, this interim registry analysis demonstrates real-world use of the dmt in assessing pigmented macules concerning for lm. over 1/3 of the melanomas reported in the registry were lm subtypes. linc had a higher correlation with the lentigo maligna subtype of melanoma and was present in all invasive tumors. while ajmh is considered borderline, it may be worthwhile in the clinical context to group ajmh lesions with lm due to similarities in treatment. ~8000 tests performed 1021 (12.8%) positive for >1 biomarker 1003 (98.2%) records available 134 (13.4%) melanomas 46 (34.3%) lm/lmm 869 (86.6%) nonmelanomas 7 (0.8%) ajmh table: correlation of genomic markers with lm/lmm/ajmh total % lmm lm ajmh linc/prame/tert 17 32.1% 4 9 4 linc/prame 14 26.4% 1 12 1 linc 10 18.9% 2 7 1 prame 5 9.4% 0 5 0 linc/tert 4 7.5% 0 4 0 tert 3 5.7% 0 2 1 the group of 53 lm/lmm/ajmh were analyzed for genomic marker correlation. linc was the most commonly expressed genomic marker (n=45, 84.9%), with prame (n=36, 67.9%) and tert (n=24, 45.3%) following. most invasive tumors (lmm) expressed all three markers (n=4) and all 7 expressed linc. these data are included in the table. the objective of this study was to examine the genomic makeup of the lm subtype of melanomas, as well as ajmh which are histopathologically borderline but often treated similarly to lm. presented at the winter clinical dermatology conference january 13-18, 2023 microsoft word september 2020 rescomp 931 proof returned.docx skin september 2020 volume 4 issue 5 copyright 2020 the national society for cutaneous medicine 431 resident competition research articles sentinel lymph node predictors in melanoma of breslow thickness 0.8-1.0 mm luisa christensen, md1, david carr, md2, sheena hill, md1, elizabeth ramser, md3, jaime abraham perez, phd4, jeremy bordeaux, md, mph1 1department of dermatology, university hospitals cleveland medical center, cleveland, oh 2department of internal medicine, division of dermatology, the ohio state university wexner medical center, columbus, oh 3department of dermatology, ohio health riverside methodist hospital, columbus, oh 4department of clinical research, university hospitals cleveland medical center, cleveland, oh the prognosis, management, and surveillance of patients with cutaneous melanoma (cm) is primarily based on staging adopted by the american joint committee on cancer (ajcc).1 the ajcc identifies patients with thin melanomas (≤ 1.0 mm in breslow thickness) as having an overall abstract introduction: current melanoma staging guidelines consider all patients staged t1b to have the same metastatic risk and recommends that sentinel lymph node biopsy (slnb) be considered in this disparate group. the goals of this study were to specifically determine predictors of sentinel lymph node positivity and those predictive for obtaining a slnb in melanomas of breslow thickness 0.8 mm to 1.0 mm, which has not been previously studied. methods: retrospective review between january 1997 and july 2019 of patients with melanomas between 0.8 mm-1.0 mm in thickness. patient demographics and primary tumor characteristics were correlated with sln status. results: of the 458 patients found to meet breslow thickness criteria, 223 (61.8%) underwent slnb. multivariate analyses demonstrated that < 60 years of age (or 2.42), increasing breslow thickness (or 1.27), mitotic rate >1 (or 2.32) and presence of tumor infiltrating lymphocytes (or 3.33), were associated with performing a slnb. positive slnb was found in 20 (8.1 %). univariate analyses revealed females (p=0.016) to have an increased risk for positive slnb. limitations: limited number of positive sln and survival data available. conclusions: younger age, breslow thickness ≥0.9 mm, mitotic rate >1, and presence of tumor infiltrative lymphocytes were found to be factors predictive of performing slnb. female gender significantly increased the odds of a positive sln. introduction skin september 2020 volume 4 issue 5 copyright 2020 the national society for cutaneous medicine 432 favorable prognosis with low probability of metastatic spread.2 however, a small percentage of these patients may go on to develop advanced disease. based on the shared 5%-10% metastatic risk in patients with primary melanoma of breslow thickness < 0.8 mm with ulceration and 0.8 mm – 1.0 mm with or without ulceration, these two different patient cohorts are staged as t1b and the national comprehensive cancer network (nccn) melanoma guidelines recommend considering slnb in these two populations.3 the potential metastatic risk in patients with thin melanomas has led to an extensive attempt to determine predictors of sentinel lymph node (sln) positivity in thin melanomas, of which primary tumor thickness and ulceration have been shown to be the most important factors associated with a positive sentinel lymph node.4 additional clinicopathologic factors, for which a prognostic value is less clear due to variability among studies, include clark level, mitotic rate, lymphovascular invasion, anatomic site, tumor infiltrating lymphocytes, regression, and patient characteristics such as gender and age.5-12 interestingly, melanomas of breslow thickness between 0.8 mm to 1.0 mm are considered to have the same risk for positive sln regardless of any other associated risk factors, and the nccn recommends considering slnb in this population, along with thinner melanomas (< 0.8 mm) with ulceration3. however, if ulceration and other patient and tumor characteristics are independent predictive factors of progression and survival, we would expect that patients whose melanomas are associated with other risk factors would have a higher likelihood for regional metastasis. to our knowledge, no studies have been conducted regarding sln predictors in this specific population. therefore, we sought to determine predictive factors for performing slnb and those predictive of positive sln in this particular cohort. after approval by the university hospitals cleveland medical center institutional review board (irb). electronic records of patients with biopsy-proven melanoma were reviewed at our institution from january 1, 1997 through july 31, 2019. patients who met criteria for breslow thickness between 0.8 mm and 1.0 mm were initially identified through our electronic pathology record system, copath. medical records were then reviewed to identify patients who did and did not have a slnb at the time of primary tumor excision. patients were excluded if they had a previous history of other thicker melanomas or if no data on sln outcomes were available. patient demographics, primary tumor characteristics, and nodal status data were collected. statistical methods study covariates included in the analyses were age at diagnosis, gender, anatomic site, breslow thickness, histologic type, dermal mitotic rate (mr), ulceration, regression, clark level, lymphovascular invasion (lvi) and tumor infiltrating lymphocytes (til). age at diagnosis was categorized into groups (< 60 years, ≥ 60 years). mr was grouped as < 1 or ≥ 1. tumor site was designated as head and neck, trunk, upper extremities, lower extremities, or genitalia. ulceration, regression, and lvi, and til were classified as being present or absent. the primary aim of this study was to identify predictors for performing a slnb. multiple logistic regression was used to investigate associations between study covariates and methods skin september 2020 volume 4 issue 5 copyright 2020 the national society for cutaneous medicine 433 whether a slnb was performed. estimates of odds ratios (or) and 95% confidence intervals (ci) were provided to evaluate the effects of these associations. using this analytical framework, we further investigated predictors for slnb positivity (within slnbperformed patient group). a p-value ≤ 0.05 was considered statistically significant. all statistical analyses were performed by using r version 3.6.2 (2019). a total of 10,206 patients diagnosed with primary cutaneous melanoma were identified, of which 458 met criteria for breslow thickness between 0.8 mm and 1.0 mm. a total of 87 patients were excluded, leaving a cohort of 361 patients available for analysis (figure 1). of these, 223 (62.8%) underwent slnb and 138 (51.3%) did not (table 1). univariate analyses demonstrated that age, breslow thickness, clark level, histologic type, mr, and tils were significantly different between patients in which slnb was performed and not performed. no difference was found among gender, anatomic location, ulceration, regression, and lvi. multivariate analyses using these six significant variables demonstrated in univariate analysis revealed that patients 60 years or younger (or = 2.42, 95% ci = 1.48-4.01), increasing breslow thickness (0.9 mm: or=1.27, 95% ci=0.732.21; 1 mm: or=2.44, 95% ci=1.26-4.88), mr > 1 (or=2.32, 95% ci=1.19-4.8), and presence of tils (or=3.33, 95% ci=1.726.61), significantly predicted whether patients underwent slnb (table 2). clark level and histologic type were not significant in predicting whether patients underwent slnb. within the subset of patients that underwent slnb, 20 (8.9%) were found to be positive and 203 (91.1%) negative (table 3). the majority of patients were male (53.8%), however the positive slnb group was predominately composed of female patients (70.0%). univariate analyses found significant differences in patient gender, with females having an increased risk for positive slnb (or=3.66, 95% ci=1.34-11.67, p= 0.016) as compared to males. no other variables were significant. figure 1 breakdown of patient selection. slnb, sentinel lymph node biopsy. to our knowledge, this is the first study reporting predictors for performing slnb in patients with thin melanomas, specifically those measuring 0.8-1.0 mm. our results showed that younger age (<60 years), breslow thickness (≥0.9 mm), mitoses (>1), and presence of til were all predictive factors for performing slnb at our institution. the strong evidence in support of breslow tumor thickness and mitoses as factors independently predictive of melanoma outcomes led to their incorporation into ajcc staging.1 at our institution, we follow ajcc/nccn guidelines to stage melanomas and provide recommendations. although mitoses are no longer used in staging of thin melanomas, this was a risk factor used in previous ajcc staging editions and explains results discussion skin september 2020 volume 4 issue 5 copyright 2020 the national society for cutaneous medicine 434 table 1. patient demographics and primary tumor characteristics for patients in which slnb was and was not performed. abbreviations: slnb, sentinel lymph node biopsy; lvi, lymphovascular invasion; tils, tumor-infiltrating lymphocytes. table 2. multivariable logistic regression analysis for predictors of undergoing slnb (performed on significant variables demonstrated in univariable analysis) variable or 95% ci p value age ≥ 60 <60 2.42 reference 1.48 to 4.01 < 0.001 gender male female 0.72 reference 0.43 to 1.18 0.197 breslow thickness (mm) 0.8 0.9 1 1.27 2.39 reference 0.73 to 2.21 1.26 to 4.88 0.032 clark level i – iii iv – v 1.40 reference 0.79 to 2.46 0.246 mitotic rate per mm2 ≤ 1 > 1 2.32 reference 1.19 to 4.8 0.014 tils absent present 3.33 reference 1.72 to 6.61 < 0.001 histologic type superficial spreading acral lentiginous lentigo maligna nodular other 0.92 0.46 0.54 0.65 reference 0.26 to 3.35 0.23 to 0.92 0.04 to 3.83 0.21 to 2.01 0.235 ulceration absent present 1.55 reference 0.46 to 6.21 0.489 abbreviations: slnb, sentinel lymph node biopsy; or, odds ratio; ci, confidence interval; tils, tumor-infiltrating lymphocytes. why mitotic rate may have been considered when recommending slnb in this specific group. when management recommendations are not clearly stated in nccn guidelines, we follow an evidence-based approach to provide appropriate recommendations. although younger age (<60 years) is not used as part of melanoma staging per ajcc, this patient-specific factor has been shown to be an important independent predictor of melanoma outcomes13 and its association with a positive slnb in thin melanomas has slnb performed (n = 223) slnb not performed (n = 138) p value characteristic no. (%) no. (%) age, years < 60 ≥ 60 130 (59.4) 89 (40.6) 99 (45.2) 120 (54.8) 31 (14.2) 78 (35.6) 52 (23.7) 57 (26) 1 (0.5) 90 (41.1) 64 (29.2) 65 (29.7) 175 (79.9) 23 (10.5) 2 (0.9) 7 (3.2) 9 (4.1) 3 (1.4) 42 (19.2) 175 (79.9) 2 (0.9) 11 (5) 208 (95) 88 (40.1) 130 (59.4) 1 (0.5) 28 (12.8) 185 (84.5) 6 (2.7) 24 (10.9) 192 (87.7) 3 (1.4) 197 (88.3) 16 (7.3) 6 (2.7) 47 (34.1) 91 (65.9) 66 (47.8) 72 (52.2) 23 (16.6) 51 (37) 40 (29) 24 (17.4) 0 79 (57.3) 40 (28.9) 19 (13.8) 89 (64.5) 30 (21.7) 2 (1.5) 6 (4.4) 10 (7.2) 1 (0.7) 41 (29.7) 95 (68.8) 2 (1.5) 4 (3) 134 (97) 112 (81.2) 26 (18.8) 0 23 (16.7) 115 (83.3) 0 0 138 (100) 0 103 (74.6) 35 (25.4) 0 < 0.001 gender female male 0.728 location head and neck trunk upper extremities lower extremities genitalia 0.234 breslow thickness (mm) 0.8 0.9 1.0 <0.001 histologic type superficial spreading lentigo maligna nodular acral lentiginous other unknown 0.022 clark level ≤ iii ≥ iv unknown 0.019 ulceration present absent 0.327 mitotic rate per mm2 <1 > 1 unknown < 0.001 regression present absent unknown 0.276 lvi present absent unknown 0.086 tils present absent unknown < 0.001 skin september 2020 volume 4 issue 5 copyright 2020 the national society for cutaneous medicine 435 table 3. patient demographics and primary tumor characteristics for positive and negative slnb. positive slnb (n = 20) negative slnb (n = 203) p value characteristic no. (%) no. (%) age, years < 60 ≥ 60 11 (55) 9 (45) 14 (70) 6 (30) 2 (10) 4 (20) 6 (30) 8 (40) 0 9 (45) 4 (20) 7 (35) 17 (85) 1 (5) 0 1 (5) 1 (5) 0 2 (10) 18 (90) 0 0 20 (100) 9 (45) 11 (55) 0 5 (25) 15 (75) 0 1 (5) 19 (95) 0 18 (90) 2 (10) 0 121 (59.6) 82 (40.4) 88 (43.3) 115 (56.7) 30 (14.8) 75 (36.9) 47 (23.2) 50 (24.6) 1 (0.5) 83 (40.9) 61 (30) 59 (29.1) 160 (78.8) 22 (10.8) 2 (1) 6 (3) 9 (4.4) 4 (2) 40 (19.7) 161 (79.3) 2 (1) 11 (5.4) 192 (94.6) 82 (40.4) 120 (59.1) 1 (0.5) 23 (11.3) 174 (85.7) 6 (3) 23 (11.3) 177 (87.2) 3 (1.5) 180 (88.6) 17 (8.4) 6 (3) 0.738 gender female male 0.010 location head and neck trunk upper extremities lower extremities genitalia 0.314 breslow thickness (mm) 0.8 0.9 1.0 0.378 histologic type superficial spreading lentigo maligna nodular acral lentiginous other unknown 0.859 clark level ≤ iii ≥ iv unknown 0.298 ulceration present absent 0.154 mitotic rate per mm2 < 1 ≥ 1 unknown 0.657 regression present absent unknown 0.271 lvi present absent unknown 0.459 tils present absent unknown 0.885 abbreviations: slnb, sentinel lymph node biopsy; lvi, lymphovascular invasion; tils, tumor-infiltrating lymphocytes. been demonstrated in several studies.9-12 our results show that younger age (<60 years) is a predictive factor for performing slnb and thus aligns with currently published data demonstrating an increased risk for positive slnb in this population. why the presence of til is a predictive factor for performing slnb is less clear. there is conflicting evidence regarding the association between til and regional nodal metastasis in melanoma. although some studies have reported a lower risk for positive slnb in melanomas with til,14-18 others have not shown such a relationship.8-9,19-21 absence of til has been demonstrated to be an independent predictor of sln positivity.14,22 it is unlikely that patients in our cohort underwent slnb based on til alone given the available evidence. the results are possibly due to the relatively small number of cases. further studies are needed to specifically determine the significance of til in thin melanomas, if any. although several studies have attempted to evaluate clinicopathologic predictors of sln positivity in thin melanomas, no study has specifically looked at melanomas measuring 0.8 to 1.0 mm in thickness. thus, we reviewed our cohort to determine which characteristics were predictive of sln positivity in this specific population. our results revealed that female gender significantly increases the odds of having a positive sln. this correlates with the findings from wright et al.10 but contrasts with other studies in which male gender was found to increase regional metastatic risk.9,23 given the inconsistency among reports, no consensus currently exists regarding the association between gender and risk for metastasis in thin melanomas. ulceration has been reported to be an important risk factor in patients with thin melanomas.7,9,24-31 as a result, ajcc designates a more advanced stage for skin september 2020 volume 4 issue 5 copyright 2020 the national society for cutaneous medicine 436 melanomas with breslow thickness <0.8 mm with ulceration as compared to melanomas <0.8 mm without ulceration. interestingly, melanomas of breslow thickness 0.8-1 mm are given the same stage regardless of ulceration status. this grouped staging is likely the result of variability in data and lack of a strong correlation between ulceration and metastatic risk as thin melanomas become thicker. our study, which focuses on this very specific group, revealed zero patients with ulcerated melanomas in the positive slnb group. all patients with ulcerated melanomas (n=11) had a negative slnb. thus, no increased risk for sln metastasis was found based on ulceration alone. other patient and tumor characteristics variably reported in the literature to increase the risk for positive sln, including age, breslow thickness, mitotic rate, clark level, til, and regression, were not found to significantly increase the risk for positive slnb in this group. limitations to our study include its retrospective and single institution nature, likely introducing selection bias, and a limited number of cases available for review, making it difficult to statistically assess for significant differences. several other studies have encountered a similar limitation given that certain tumor traits, such as ulceration and sln metastasis, in thin melanomas are uncommon. moreover, we attempted to study survival outcomes in this group, but there were not enough cases with a positive sln or survival data available for a significant statistical analysis. in summary, our study represents the first analysis of predictors of performing slnb and of increased risk for positive sln in patients with melanomas of breslow thickness between 0.8 and 1.0 mm. our results revealed that younger age (<60 years), increased breslow thickness (≥0.9 mm), mitotic rate >1, and presence of til were predictive factors of performing slnb. female gender was found to be the only statistically significant factor to increase the risk for positive sln. we believe these findings can potentially improve management recommendations and enhance patient care. conflict of interest disclosures: none funding: none corresponding author: luisa christensen, md 11100 euclid ave cleveland, oh 44106 email: luisa.christensen@uhhospitals.org references: 1. american joint committee on cancer. ajcc cancer staging manual. 8th ed. springer international publishing; 2017. 2. andtbacka rh, gershenwald je. role of sentinel lymph node biopsy in patients with thin melanoma. j natl compr canc netw. 2009 mar;7(3):308-17. 3. national comprehensive cancer network. cutaneous melanoma (version 3.2020). https://www.nccn.org/professionals/physician_gls/p df/cutaneous_melanoma.pdf. accessed june 17, 2020. 4. yonick dv, ballo rm, kahn e, et al. predictors of positive sentinel lymph node in thin melanoma. am j surg. 2011 mar;201(3):324-7 5. munsch c, lauwers-cances v, lamant l, et al. breslow thickness, clark index and ulceration are associated with sentinel lymph node metastasis in melanoma patients: a cohort analysis of 612 patients. dermatology. 2014;229(3):183-9. 6. cavanaugh-hussey mw, mu ew, kang s, et al. older age is associated with a higher incidence of melanoma death but a lower incidence of sentinel lymph node metastasis in the seer databases (2003-2011). ann surg oncol. 2015 jul;22(7):21206. 7. han d, zager js, shyr y, et al. clinicopathologic predictors of sentinel lymph node metastasis in thin melanoma. j clin oncol. 2013 dec 10;31(35):438793. 8. cordeiro e, gervais m, shah ps, et al. sentinel lymph node biopsy in thin cutaneous melanoma: a systematic review and meta-analysis. ann surg oncol. 2016; 23:4178–4188. conclusion skin september 2020 volume 4 issue 5 copyright 2020 the national society for cutaneous medicine 437 9. conic rrz, ko j, damiani g. predictors of sentinel lymph nodepositivity in thin melanoma using the national cancer database. j am acad dermatol. 2019;80:441-7. 10. wright be, scheri rp, ye x, et al. importance of sentinel lymph node biopsy in patients withthin melanoma. arch surg. 2008 sep;143(9):892-9. 11. venna ss, thummala s, nosrati m, et al. analysis of sentinel lymph node positivity in patients with thin primary melanoma. j am acad dermatol. 2013;68:560-567. 12. sondak vk, taylor jm, sabel ms, et al. mitotic rate and younger age are predictors of sentinel lymph node positivity: lessons learned from the generation of a probabilistic model. ann surg oncol. 2004;11:247-258. 13. khosrotehrani k, dasgupta p, byrom l, et al. melanoma survival is superior in females across all tumor stages but is influenced by age. arch dermatol res. 2015;307:731-40. 14. taylor rc, patel a, panageas ks, et al. tumorinfiltrating lymphocytes predict sentinel lymph node positivity in patients with cutaneous melanoma. j clin oncol. 2007;25:869-875. 15. clark wh jr, elder de, guerry dt, et al. model predicting survival in stage i melanoma based on tumor progression. j natl cancer inst. 1989;81:1893-1904. 16. clemente cg, mihm mc jr, bufalino r, et al. prognostic value of tumor infiltrating lymphocytes inthe vertical growth phase of primary cutaneous melanoma. cancer. 1996;77:1303-1310. 17. sondergaard k, schou g: survival with primary cutaneous malignant melanoma, evaluated from 2012 cases: a multivariate regression analysis. virchows arch a pathol anat histopathol. 1985;406:179-195. 18. johnson ok jr, emrich lj, karakousis cp, et al. comparison of prognostic factors for survival and recurrence in malignant melanoma of the skin, clinical stage i. cancer. 1985; 55:1107-1117. 19. larsen te, grude th: a retrospective histological study of 669 cases of primary cutaneous malignant melanoma in clinical stage i: the relation between the tumour-associated lymphocyte infiltration and age and sex, tumour cell type, pigmentation, cellular atypia, mitotic count, depth of invasion, ulceration, tumour type and prognosis. acta pathol microbiol scand. 1978;86a:523-530. 20. barnhill rl, fine ja, roush gc, et al. predicting five-year outcome for patients with cutaneous melanoma in a population-based study. cancer. 1996;78: 427-432. 21. thorn m, ponten f, bergstrom r, et al. clinical and histopathologic predictors of survival in patients with malignant melanoma: a population based study in sweden. j natl cancer inst. 1994;86:761-769. 22. kruper l, botbyl b, czerniecki b, et al. sentinel lymph node status in stage ii/iii melanoma. j clin oncol. 2005;23:710s (suppl; abstr 7501). 23. gimotty pa, guerry d, ming me, et al. thin primary cutaneous malignant melanoma: a prognostic tree for 10-year metastasis is more accurate than american joint committee on cancer staging. j clin oncol. 2004;22:3668–3676. 24. mozzillo n, pennacchhioli e, gandini s, et al. sentinel node biopsy in thin and thick melanoma. ann surg oncol. 2013;20(8):2780–6. 25. stitzenberg kb, groben pa, stern sl, et al. indications for lymphatic mapping and sentinel lymphadenectomy in patients with thin melanoma (breslow thickness b1.0 mm). ann surg oncol. 2004;11(10): 900-6. 26. ranieri jm, wagner jd, wenck s, et al. the prognostic importance of sentinel lymph node biopsy in thin melanoma. ann surg oncol. 2006;13(7):927– 32. 27. wong sl, faries mb, kennedy eb, et al. results of sentinel lymph node biopsy in patients with thin melanoma. ann surg oncol. 2006;13(3):302–9. 28. cecchi r, buralli l, innocentu, de gaudio c. sentinel lymph node biopsy in patients with thin melanomas. j dermatol. 2007;34(8):512–5. 29. vermeeren l, van der ent, sastrowijoto p, hulsewe. sentinel lymph node biopsy in patients with thin melanoma: occurrence of nodal metastases and its prognostic value. eur j dermatol. 2010;20(1):30–34. 30. murali r, haydu le, quinn mj, et al. sentinel lymph node biopsy in patients with thin primary cutaneous melanoma. ann surg. 2012;255(1):128–31. mitteldorf c, bertsch hp, jung k, et al. sentinel node biopsy improves prognostic stratification in patients with thin (pt1) melanomas and an additional risk factor. ann surg oncol. 2014;21(7):2252–8. microsoft word september 2020 dh 969 proof.docx skin september 2020 volume 4 issue 5 copyright 2020 the national society for cutaneous medicine 489 dermatologic history norman orentreich: father of modern hair transplantation michael phan bs1, jonathan phan ms1 1university of texas medical branch, school of medicine, galveston tx norman orentreich, md is universally regarded as the father of modern hair transplantation. he was born in new york city on december 26, 1922. he completed his undergraduate studies at the college of new york and served in the us navy medical corps from 1943-1945. dr. orentriech attended medical school at the new york university of college of medicine and received his dermatology training at nyu’s skin and cancer unit.1 while studying the pathophysiology of diverse dermatologic conditions using hairbearing punch grafts in the early 1950s, he observed that autografts from hair-bearing areas of the scalp continued to grow hair when implanted in areas of physiological male-pattern alopecia.2 this observation established the principle of donor dominance: transplanted autografts maintained their integrity and characteristics independent of the recipient site. after successfully transplanting hair in 65 patients, he published his results in 1959.2 dr. orentreich understood the limitations of his technique and sought methods to improve his patient’s cosmetic outcomes. by 1985, he created minigrafts containing three to five hairs and overlapped his grafts to address patchy hair growth. dr. orentreich also incorporated the use of intralesional corticosteroid to prevent hypertrophic and keloidal scarring and dermabrasion to treat elevated grafts.3 his follicle-preserving extraction technique paved way for the development of follicular unit transplantation and extraction.1 dr. orentreich’s interests extend beyond hair transplantation. he founded the orentreich foundation for the advancement of science for aging and nutrition research in 1961. in 1968, the lauder family recruited dr. orentreich and vogue editor skin september 2020 volume 4 issue 5 copyright 2020 the national society for cutaneous medicine 490 carol phillips to create clinique, the world’s first allergy-tested, fragrance-free, dermatologist-guided cosmetic line. he was also elected the first president of the american society for dermatologic surgery in 1970.1 dr. orentreich established the current field of hair transplantation with his visionary discoveries. his contributions to dermatology have benefited many people with hair loss in the 20th century. conflict of interest disclosures: none funding: none corresponding author: michael phan 1005 harborside dr f5 galveston, tx 77555 email: miphan@utmb.edu references: 1. refs orentreich medical group. our founder. http://orentreich.com/about-us/our-founder/. accessed july 6, 2020. 2. orentreich n. autografts in alopecias and other selected dermatological conditions. ann n y acad sci. 1959;83:463-479. doi:10.1111/j.17496632.1960.tb40920.x 3. orentreich ds, orentreich n. hair transplantation. j dermatol surg oncol. 1985;11(3):319-324. doi:10.1111/j.15244725.1985.tb03010.x patient tolerability of tazarotene foam, 0.1%, and impact on patient compliance a multicenter, open-label, phase 1 study of the safety, tolerability, systemic exposure, pharmacodynamics, and treatment effect of calcipotriene foam, 0.005% in pediatric subjects (ages 2 to 11 years) with plaque psoriasis. adelaide a. hebert, mda; debbie glaab msn, cpnp-acb; rhonda schreiber msrnb , calcipotriene foam, 0.005%, was well tolerated with a low incidence of adverse events in the pediatric population. there were no quantifiable systemic concentrations of calcipotriene nor effect seen on calcium metabolism with repeated application. while this study was not designed as an efficacy study, the % of subjects who were isga responders was found to be consistent with the efficacy in the treatment of body and scalp in adults. overall, the results in this pediatric population are consistent with previously reported clinical findings for adolescents and adults indicating that calcipotriene foam, 0.005% is safe, well tolerated, and effective treatment option for pediatric psoriasis patients. conclusions • phase 1 multicenter, open-label, repeat-dose study with 36 subjects ages 2 to 11 years from 16 sites. • two cohorts: • maximum use cohort defined as isga score of 3 or higher at screening and at least 3% body surface index (bsa) with some scalp involvement. • general use cohort defined as isga score of 2 or 3 at screening with no bsa minimum • subjects or their caregivers applied a thin layer of study product twice a day to the treatment areas (excluding the face) for 8 weeks: • in the event that the lesions cleared prior to the end of the study, subjects or their primary caregivers were to continue to apply study product to treatment areas originally affected by psoriasis. • any new psoriatic lesions which appeared in treatment areas during the treatment period were also treated with the study product. • safety assessments (adverse event and serious adverse event query) occurred at all study visits. • treatment effect, urine calcium metabolism, and application site tolerability assessments were performed for all subjects at all in-clinic visits. • blood samples were taken from all subjects at screening for evaluation of pharmacodynamic (pd) assessments and 25-oh vitamin d levels at baseline, and an additional blood draw for pd parameters was taken at week 2 for the maximum-use cohort only. • the % of subjects who were isga responders was compared to the phase iii adult clinical trial results using bayesian analysis. methods resultssynopsis primary objective: • to evaluate the safety and tolerability of calcipotriene foam, 0.005%, in pediatric subjects, ages 2 to 11 years, with mild to moderate plaque psoriasis. secondary objectives: • to evaluate the pharmacodynamic effect on calcium metabolism of calcipotriene foam 0.005%, in pediatric subjects, ages 2 to 11 years, with mild to moderate plaque psoriasis. • to describe the plasma concentrations of calcipotriene following administration of calcipotriene foam, 0.005% in pediatric subjects, ages 2 to 11 years, with moderate plaque psoriasis. • to describe the treatment effect of calcipotriene foam, 0.005%, in pediatric subjects, ages 2 to 11 years, with mild to moderate plaque psoriasis. objectives • pd markers showed a general lack of change over time and there were no quantifiable systemic concentrations of calcipotriene observed. the average values of corrected calcium, magnesium and phosphorus were consistent over time. the ipth and alkaline phosphatase showed some variability across time, but no consistent trends and similar values at screening and day 15. the variability in these values could likely be attributed to small sample size, especially in the subgroups. there was no relationship seen between urinary calcium/creatinine ratio and %bsa treated or age. • no serious adverse events were reported. of the 29 adverse events that were reported; 7 were considered related to the treatment. these adverse events presented themselves as mostly topical in nature. local tolerability results remained 0 from baseline to study end in 22 subjects (61.11%). • no evidence of a drug effect was noted for body weight, height, or vital signs. • isga scores improved with treatment, but differences between treatments could not be assessed because of the small number of subjects receiving vehicle and the study was not designed to show efficacy. however, response rates (% of subjects with an isga score of 0 or 1 for body or scalp at week 8) were consistent with that observed in the double-blind, vehicle controlled phase iii studies in adults. pd marker visit calcipotriene (cal) vehicle n mean (sd) min max n mean (sd) min max corrected calcium (mmol/l) screening 21 9.3 (0.22) 8.8 9.7 2 9.4 (0.14) 9.3 9.5 day 1 3 9.1 (0.17) 9.0 9.3 2 9.1 (0.07) 9.0 9.1 day 13 16 7 9.2 (0.24) 8.9 9.6 2 9.4 (0.35) 9.1 9.6 day 56 59 3 9.3 (0.35) 9.0 9.7 2 9.4 (0.14) 9.3 9.5 ipth (pmol/l) screening 19 29.0 (10.54) 12.0 46.0 2 54.0 (53.74) 16.0 92.0 day 1 3 45.0 (23.00) 22.0 68.0 2 49.0 (26.87) 30.0 68.0 day 13 16 7 32.1 (23.58) 16.0 84.0 2 25.0 (9.90) 18.0 32.0 day 56 59 3 49.7 (49.10) 16.0 106.0 2 26.5 (0.71) 26.0 27.0 alkaline phosphatase (µ/l) screening 21 274.4 (69.43) 160.0 415.0 2 267.0 (69.30) 218.0 316.0 day 1 3 357.7 (121.18) 221.0 452.0 2 272.0 (77.78) 217.0 327.0 day 13 16 6 292.3 (99.83) 184.0 446.0 2 296.0 (106.07) 221.0 371.0 day 56 59 3 316.7 (110.59) 190.0 394.0 2 279.0 (28.28) 259.0 299.0 magnesium (mmol/l) screening 21 1.8 (0.10) 1.6 1.9 2 1.6 (0.00) 1.6 1.6 day 1 3 1.7 (0.21) 1.5 1.9 2 1.7 (0.21) 1.5 1.8 day 13 16 6 1.7 (0.15) 1.5 1.9 2 1.7 (0.14) 1.6 1.8 day 56 59 3 1.8 (0.15) 1.6 1.9 2 1.6 (0.00) 1.6 1.6 phosphorus (mmol/l) screening 21 5.0 (0.47) 3.5 5.8 2 4.6 (0.42) 4.3 4.9 day 1 3 5.1 (0.06) 5.0 5.1 2 4.3 (0.42) 4.0 4.6 day 13 16 6 4.8 (0.56) 4.1 5.6 2 4.4 (0.49) 4.0 4.7 day 56 59 3 5.3 (0.46) 5.0 5.8 2 4.8 (0.21) 4.6 4.9 calcium/creatinine (mg/g creat) screening 18 77.0 (43.57) 11.0 172.0 2 101.5 (64.35) 56.0 147.0 day 1 21 66.9 (76.84) 7.0 286.0 2 101.5 (64.35) 56.0 147.0 day 13 16 18 72.5 (56.57) 7.0 220.0 2 67.0 (29.70) 46.0 88.0 day 56 59 19 90.2 (80.83) 5.0 285.0 2 61.0 (36.77) 35.0 87.0 pd marker at screening, day 1, day 13-16 and day 56-59 a. ut health mcgovern medical school-houston, houston, tx; b. mayne pharma, greenville, nc. this study and analysis was sponsored by mayne pharma. all research funding was paid to ut health mcgovern medical schoolhouston, houston, tx. affiliations and disclaimers references teae type n (%) # of events overall 6 (16%) 7 application site pain 2 (6.3%) 2 contact dermatitis 2 (6.3%) 2 psoriasis 3 (9.4%) 3 relative change from day 1 to day 15 and day 22 for pd markers summary of treatment emergent adverse events* *no aes reported in vehicle control group pd marker treatment n geometric mean 95% ci 90% ci corrected calcium (mmol/l) cal 7 0.997 0.976 1.018 0.971 1.024 vehicle 2 0.994 0.898 1.101 0.810 1.220 ipth (pmol/l) cal 7 1.069 0.697 1.639 0.624 1.831 vehicle 2 0.626 0.015 25.445 0.000 1083.9 alkaline phosphatase (u/l) cal 6 0.955 0.872 1.045 0.851 1.071 vehicle 2 1.091 0.686 1.734 0.429 2.772 magnesium (mmol/l) cal 6 0.971 0.923 1.021 0.910 1.035 vehicle 2 1.061 0.731 1.538 0.502 2.242 phosphorus (mmol/l) cal 6 0.991 0.907 1.082 0.885 1.109 vehicle 2 0.945 0.857 1.041 0.777 1.148 body n (%) scalp n (%) calcipotriene foam, 0.005% 14 (45.16) 19 (61.29) vehicle foam 1 (33.3) 1 (33.3) % subjects with isga score 0 or 1 at week 8 demographics calcipotriene foam, 0.005% n=32 vehicle foam n=4 demographics calcipotriene foam, 0.005% n=32 vehicle foam n=4 age (yrs) mean (sd) median min, max 8.6 (2.06) 9 4,11 8.5 (2.65) 9 5,11 baseline bsa: (%) mean (sd) median min,max 12.2 (9.94) 7.8 0.5,36.5 16.5 (8.26) 19.1 5,23 race: n (%) caucasian african american asian native american/alaskan other 25 (78) 4 (13) 0 1 (3) 2 (6) 3 (75) 0 1 (25) 0 0 baseline isga body mean sd median min,max baseline isga scalp mean sd median min,max 2.5 (0.92) 3 0,4 1.9 (1.34) 2 0,4 3 (0) 3 3,3 2.8 (0.50) 3 2,3 gender: n (%) male female 15 (47) 17 (53.) 2 (50) 2 (50) height (cm) mean sd median min,max 136.2 (13.91) 137.2 104,159 129.2 (11.59) 124.2 122,147 ethnicity: n (%) hispanic/latino not hispanic/latino 13 (42) 18 (58) 1 (25) 3 (75) weight (kg) mean sd median min,max 42.1 (15.56) 41.6 17.8,77.1 36.2 (12.23) 35.3 22.7,51.3 1. national psoriasis foundation. (2019, july 31). about psoriasis. retrieved from psoriasis.org: www.psoriasis.org/parents/about-psoriasis. 2. silverberg, n. b. (2009). pediatric psoriasis: an update. therapeutics and clinical risk management, 5, 849856. 3. kimball, a., gold, m., zib, b., davis, m., & clobetasol propionate emulsion formulation foam ph. (2008). clobetasol propionate emulsion formulation foam 0.05%: review of phase ii open-label and phase iii randomized controlled trials in steroid-responsive dermatoses in adults and adolescents. jaad, 59(3), 448-454. 4. shah, k. n. (2013). diagnosis and treatment of pediatric psoriasis: current and future. american journal of clinical dermatology, 14, 195. 5. wolverton, s. e. (2001). comprehensive dermatologic drug therapy (xlx ed.). philadelphia, pa: saunders. 6. feldman , s. r., mills, m., brundage, t., & eastman, w. j. (2013, march). a multicenter, randomized, double-blind study of the efficacy and safety of calcipotriene foam, 0.005%, vs vehicle foam in the treatment of plaque-type psoriasis of the scalp. jdd, 12(3), 300-306. 7. hebert, a., glaab, d., & schrieber, r. (2019). a phase 1 open label multicenter study to evaluate the safety, tolerability, pharmacodynamics, and pharmacokinetics of calcipotriene foam, 0.005% applied under maximum use conditions in adolescent subjects with plaque psoriasis. skin: the journal of cutaneous medicine, 3(2). response rates for pediatric and adults from previous studies according to the national psoriasis foundation approximately 150,000 new psoriasis patients are diagnosed in the united states each year.1 almost 20,000 (13%) of newly diagnosed patients are children under the age of 10 with most manifesting with plaque psoriasis (68.6%) with lesions localized to the scalp, post auricular region, elbows, and knees.2 although the relative frequency of plaque psoriasis differs between adults and children, the etiology is thought to be the same as evidenced by similar response rates to therapies.3,4 there are few therapeutic options for the pediatric population that have proven safety and efficacy and that have fda approval in the pediatric population. calcipotriene is a synthetic vitamin d3 derivative that has been used effectively for many years for the treatment of plaque-type psoriasis.5 the efficacy and safety of calcipotriene foam, 0.005%, was established in phase iii clinical trials for the treatment of adults and recently the fda adjusted the indication to include treatment in patients 12 years and older due to proven safety in a phase i study in adolescents.6,7 the data presented here highlight the results of an additional phase i clinical study in pediatric subjects aged 2 to 11 years. safety and efficacy of a-101 hydrogen peroxide topical solution 40% in adults with seborrheic keratosis: results from the phase 3, randomized, double-blind, vehicle-controlled, parallel-group study zoe d. draelos, md,1 steven e. kempers, md,2 stacy r. smith, md,3 david c. wilson, md,4 christopher v. powala,5 mark bradshaw, phd,6 esther estes, md, mph,5 stuart d. shanler, md, faad, facms5 1dermatology consulting services, high point, nc; 2minnesota clinical study center, fridley, mn; 3california dermatology & clinical research institute, encinitas, ca; 4the education and research foundation, inc., lynchburg, va; 5aclaris therapeutics, malvern, pa; 6global consulting partners in medical biometrics, new york, ny introduction • seborrheic keratosis (sk) is a common cutaneous lesion that affects more than 83 million americans,1 particularly those who are middle-aged and older. while benign, these lesions are cosmetically unacceptable to many patients. • malignancy concerns following the appearance of sk lesions act as a primary driver for a patient to seek medical advice. • removal of sks is often performed for cosmetic reasons, but it may be indicated for inflamed, pruritic, or painful lesions. • currently, there is no us fda–approved drug for the treatment of sks. however, ablative/destructive procedures (eg, cryosurgery, electrodessication/curettage, etc) are available, but their efficacy and safety have not been rigorously evaluated in well-controlled clinical trials. • a noninvasive, well-tolerated, topical agent for the removal of sk lesions is an important unmet need. • a-101, a patented investigational new drug, is a 40% hydrogen peroxide topical solution, with a surface tension–reducing agent formulated for the treatment of sk lesions.2 • phase 2 studies showed that a numerically greater percentage of subjects achieved lesion clearance when treated with a-101 40% versus a-101 32.5%; both concentrations achieved significantly greater clearance than placebo.3 • the purpose of this study was to evaluate the safety and efficacy of a-101 40% versus its matching vehicle for the treatment of sk. materials and methods patients and study design • multicenter, phase 3, randomized, double-blind, vehicle-controlled, parallel-group study. patients were randomized 1:1 to receive a-101 or matching vehicle. • eligible patients: aged ≥ 18 years with 4 eligible sk lesions, identified by study investigator. • eligible target lesions were stable, typical sks, measuring 5-15 mm in both width and length, 1-2 mm in thickness, and physician’s lesion assessment (pla) grade ≥ 2 (table 1).4 patients were required to present with ≥ 1 lesion on the trunk or extremities and ≥ 1 lesion on the face. — target lesions could not be on the eyelid, within 5 mm of the orbital rim, in an intertriginous area, or pedunculated. table 1: validated pla3 scale grade descriptor 0 clear: no visible sk lesion 1 near clear: a visible sk lesion with a surface appearance different from the surrounding skin (not elevated) 2 thin: a visible sk lesion (≤ 1 mm) 3 thick: a visible sk lesion (> 1 mm) table 2: > 90% of patients experience no local skin dyspigmentation or scarring no reaction mild moderate severe hypopigmentation a-101 40% vehicle 97.7% 99.9% 2.3% 0.1% 0.0% 0.0% 0.0% 0.0% hyperpigmentation a-101 40% vehicle 93.8% 99.8% 5.6% 0.1% 0.6% 0.1% 0.0% 0.0% scarring a-101 40% vehicle 99.3% 100.0% 0.6 % 0.0% 0.1% 0.0% 0.0% 0.0% conclusions • a-101 (figure 3), a 40% hydrogen peroxide topical solution, is a safe, effective, and well-tolerated treatment for seborrheic keratoses. • for sks on the face and cosmetically sensitive locations, a-101 was highly effective, with very low occurrence of hypopigmentation and/or scarring. • if approved, a-101 would be the first us fda–approved topical treatment for seborrheic keratosis. references 1. bickers dr, et al. j am acad dermatol. 2006;55:490-500. 2. simionescu o, et al. j cell mol med. 2012;16:1223-1231. 3. dubois jc, et al. dermatol surg, in press. 4. data on file. aclaris therapeutics inc., 2014, malvern, pa, usa. acknowledgments this study was funded by aclaris therapeutics, inc. editorial support for this poster was provided by parexel and funded by aclaris therapeutics, inc. figure 3: patient photos of target sk before and after a-101 treatment female, forehead female, temple pla-3 pla-3 pla-0 day 106 pla-1 day 106 • all treatments were performed by a nonphysician subinvestigator to maintain blinding. after initial treatment on day 1, sk lesions with a pla score > 0 were retreated on day 22. at day 106, the investigator assessed the lesions using the validated pla scale. • efficacy analyses were based on the intent-to-treat (itt) population; any subject with missing pla data on day 106 was considered a nonresponder. end points • primary efficacy endpoint: percent of patients with complete clearance (pla = 0) of all 4 lesions at 106 days after first treatment. • secondary endpoint: percent of patients with complete clearance (pla = 0) in at least 3 of 4 lesions. • exploratory endpoints: — mean per-patient percent of lesions judged clear/near clear (pla ≤ 1) — mean per-patient percent of lesions on the face judged clear/near clear (pla ≤ 1). • safety: adverse events (aes), local skin reactions. results • a total of 450 patients were enrolled—220 of 223 and 226 of 227 patients randomized to a-101 and vehicle, respectively, completed the study. • demographic characteristics were similar across all treatment groups. • mean age of patients was 69 years (range, 42–90). 59% of subjects were women, and 97.8% (440) were caucasian. • fitzpatrick types 1 to 5 were represented: — type 1: 72 (16.0%); type 2: 211 (46.9%); type 3: 123 (27.3%); type 4: 40 (8.9%); type 5: 4 (0.9%). efficacy primary and secondary endpoints • significantly more patients receiving a-101 completely cleared (pla = 0) all 4 of 4 lesions (4.0% vs 0%, p < 0.002) and 3 of 4 lesions (13.5% vs 0%, p < 0.0001) versus vehicle in the primary and secondary endpoints, respectively, at day 106 (figure 1). exploratory endpoints • significantly higher mean per-patient percentage of lesions achieving clear/near clear (pla ≤ 1) was observed in the a-101 arm (48% vs 10% at day 106; p < 0.0001) (figure 2a). • significantly higher mean per-patient percentage of facial lesions achieving clear/ near clear (pla ≤ 1) was also observed in the a-101 arm (64% vs 15% at day 106; p < 0.0001) (figure 2b). figure 1: clearance of all 4 sk lesions (a) and clearance of at least 3 of 4 sk lesions (b) 0 2 1 3 4 5 6 7 8 9 10 day 106 0 a b 0 day 106 p at ie n ts , % 0 6 8 10 12 14 4 2 16 p at ie n ts , % 4.0% 13.5% p < 0.001 p < 0.0001 vehicle a-101 40% 0 20 10 30 40 50 60 70 le si on s, % 0 30 20 10 40 50 60 70 le si on s, %48% 64% 10% 15% a b day 106 day 106 vehicle a-101 40% p < 0.001p < 0.0001 figure 2: mean per-patient percentage of lesions (a) or facial lesions (b) judged to be clear/near clear (pla ≤ 1) safety • aes were comparable between groups: 54 (24.2%) patients in the a-101 group versus 45 (19.8%) patients in the vehicle group. — the most frequently reported treatment-emergent aes were nasopharyngitis (1.3% a-101 vs 3.1% vehicle), bronchitis (1.3% a-101 vs 0.4% vehicle), and upper respiratory tract infection (0.4% a-101 vs 1.3% vehicle). — 4 (1.8%) patients in the a-101 group had 4 serious aes (saes) versus 6 (2.6%) patients in the vehicle group who had 7 saes. all saes were considered not related to study medication. • local skin reactions were predominantly mild and had generally resolved by day 106 (table 2). • at all visits, atrophy, erosion, hypopigmentation, scarring, or ulceration were reported for ≤ 4% of lesions. gs1330 aclaris fall clinical 2017 a101 s08.indd 1 15/09/2017 15:56 fc17posteraclarisdraelossafetya101hydrogenperoxide.pdf synopsis • basal cell carcinoma (bcc) is the most common cancer worldwide, with an increasing annual incidence1,2 — in patients with advanced bcc, lesions become extensively locally invasive or metastatic, and traditional first-line surgical treatment may be contraindicated3 • hedgehog pathway inhibitors (hhis) represent an alternate treatment option for patients with advanced bcc4 — hhis block the aberrant hedgehog pathway activation that allows transcription of glioma-associated oncogene transcription factors and activation of target genes for tumorigenesis and angiogenesis during development of bcc (figure 1)5 — most hhis prevent hedgehog signaling by binding to and preventing activation of transmembrane protein smoothened5 figure 1. hedgehog signaling pathway6 shh ptch smo gli transcription gli target image source: jain s, et al. oncotargets ther. 2017;10:1645–53. gli, glioma-associated oncogene; ptch, patched; shh, sonic hedgehog; smo, smoothened. • sonidegib is an hhi approved in the us, the eu, switzerland, and australia for the treatment of adult patients with locally advanced bcc that has recurred following surgery or radiation therapy or is not amenable to surgery or radiation therapy7 — recommended dosing is one 200 mg capsule by mouth daily on an empty stomach or ≥1 hour before or ≥2 hours after a meal7 ○ treatment should continue until significant toxicity or disease progression7 — administration with a high-fat meal increases drug absorption by 7.4to 7.8-fold7 • use of hhis, including sonidegib, in patients with dysphagia or impaired gastrointestinal absorption poses unique and challenging management scenarios objectives • understand the effects of high-fat foods on sonidegib absorption • raise awareness of and improve access to sonidegib for other patients with gastrointestinal absorption issues methods • an n-of-1 trial was conducted • the patient was an 83-year-old woman with history of short bowel syndrome and dysphagia — she also had a history of multiple keratinocyte carcinomas of the nose and cheek, which were previously treated with mohs micrographic surgery, radiation, and salvage radiation • the patient presented to strasswimmer mohs surgery, delray beach, fl, usa with a large, surgically unresectable, recurrent, locally advanced bcc lesion on the nasal tip — biopsy of the nose revealed a locally advanced, infiltrative bcc • considering patient factors and hhi pharmacology, half of a capsule (100 mg) of sonidegib was prescribed to be taken in 2 tablespoons of vanilla ice cream once daily — due to teratogenicity risk with sonidegib, a family member of no reproductive potential divided the capsule using medical gloves and a razor blade • efficacy was assessed via observation of tumor response • safety evaluations included monitoring for signs and symptoms of toxicity — electrolytes, liver function, and creatine kinase values were monitored • patient provided informed consent for publication results • after 5 weeks of treatment, reduction in tumor size was noted (image 1) image 1. photographs showing tumor response in patient with bcc following sonidegib treatment a. the patient upon initial presentation with an infiltrative bcc of the nose b. improvement of the patient’s infiltrative bcc after 5 weeks of sonidegib treatment bcc, basal cell carcinoma. • around week 5 of treatment, the patient began to experience adverse effects, including mild nausea and muscle cramping of the hands and feet — clinical laboratory parameters remained within normal limits — a 5-week medication holiday was subsequently instituted with symptom resolution • tumor regrowth was noted after 5 weeks without therapy, so sonidegib was reinstated at the same dose for another 5 weeks • in total, the patient completed three 5-week sonidegib cycles with 5 weeks of medication holiday between each cycle • following the third course of sonidegib, the patient and her family were satisfied with treatment results — more than 1 year later, she continues to deny further issues conclusions • combining a low dose of sonidegib with ice cream, a high-fat food, helped overcome the patient’s gastrointestinal absorption and swallowing issues • clinical improvement of bcc was noted after 5 weeks of sonidegib treatment • adverse effects included nausea and muscle cramping, though the patient’s bloodwork values remained within normal limits for the duration of treatment • the patient best tolerated a treatment regimen alternating 5 weeks on and 5 weeks off sonidegib references 1) asgari mm, et al. jama dermatol. 2015;151(9):976–81. 2) marzuka ag, book se. yale j biol med. 2015;88:167–79. 3) amici jm, et al. eur j dermatol. 2015;25(6):586–94. 4) kim jys, et al. j am acad dermatol. 2018;78(3):540–59. 5) cortes je, et al. cancer treat rev. 2019;76:41–50. 6) jain s, et al. oncotargets ther. 2017;10:1645–53. 7) odomzo® (sonidegib capsules). full prescribing information. sun pharmaceutical industries, inc., cranbury, nj, usa. 2019. acknowledgments medical writing and editorial support were provided by jennifer masucci, vmd, of alphabiocom, llc, and funded by sun pharma. disclosures hg, mc, and js report nothing to disclose. optimizing the pharmacokinetics of sonidegib in small bowel syndrome and advanced basal cell carcinoma: our solution hailey grubbs, do1; marianne cortes, bs2; john strasswimmer, md, phd3,4 1dermatology department, broward health medical center, ft lauderdale, fl, usa; 2nova southeastern university kiran c patel college of osteopathic medicine, davie, fl, usa; 3florida atlantic university, boca raton, fl, usa; 4strasswimmer mohs surgery, delray beach, fl, usa skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 876 research letter cutaneous fungal infections associated with pediatric-onset diabetes: a case-control study in the all of us research program emily strouphauer, bsa1, rajani katta, md2 1 school of medicine, baylor college of medicine, houston, tx 2 department of dermatology, mcgovern medical school at university of texas health science center at houston, houston, tx with the rapidly increasing incidence of pediatric diabetes mellitus (dm) in the united states,1 an understanding of the risk of longterm cutaneous consequences, particularly the risk of cutaneous fungal infections, is important. here, we evaluate the association between pediatric-onset type 1 diabetes (t1d) and type 2 diabetes (t2d) with the later development of cutaneous fungal infections in the all of us research program. this is a national institutes of health abstract introduction: with the rapidly increasing incidence of pediatric diabetes mellitus (dm) in the united states, an understanding of the risk of long-term cutaneous consequences, particularly the risk of cutaneous fungal infections, is important. in this study, we evaluate the association between pediatric-onset type 1 diabetes (t1d) and type 2 diabetes (t2d) with the later development of cutaneous fungal infections. methods: through the all of us electronic health record database, 300 de-identified participants with a diagnosis of t1d or t2d before the age of 18 were selected at random. these 300 participants, composing our pediatric-onset diabetes cohort, were diagnosed with t1d and/or t2d before the age of 18 and developed cutaneous fungal infections between less than 1 and 24 years later. each case was age-, race-, and sex-matched to four control participants without t1d or t2d diagnoses, and we compared cutaneous fungal infections between pediatric-onset diabetic cases and controls. results: compared to the control cohort, participants with pediatric-onset diabetes were significantly more likely to present in adulthood with candidiasis of the mouth, onychomycosis, pityriasis versicolor, candidiasis of urogenital sites, and unspecified superficial mycosis, as well as dermatophytosis of the body, feet, and perianal regions than their non-diabetic counterparts. conclusion: with the increasing incidence of pediatric dm, it will be important for clinicians to monitor the long-term cutaneous complications, including the risk of fungal infections, to improve dermatology patient outcomes. further research is warranted to investigate the role of childhood diabetes intervention and glycemic control in mitigating dermatologic fungal complications through adulthood. introduction skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 877 database presenting health information on americans who are historically underrepresented in research. through the all of us electronic health record database, we randomly selected 300 deidentified participants with a diagnosis of t1d or t2d before the age of 18. these 300 participants, composing our pediatric-onset diabetes cohort, were diagnosed with t1d and/or t2d before the age of 18 and developed cutaneous fungal infections between less than 1 and 24 years later. each case was age-, race-, and sex-matched to four control participants without t1d or t2d diagnoses. participant demographics are displayed in table 1. we compared cutaneous fungal infections between pediatric-onset diabetic cases and controls. all analyses were performed using r statistical software,2 and the results are depicted as odds ratios (or) with 95% confidence intervals (ci) in table 2. compared to the control cohort, participants with pediatric-onset diabetes were significantly more likely to present with candidiasis of the mouth (or 8.34, 3.3420.86 ci), onychomycosis (or 34.70, 10.37116.05 ci), pityriasis versicolor (or 3.56, 1.28-9.90 ci), and unspecified superficial mycosis (or 16.20, 1.80-145.51 ci) which encompasses dermatophytosis, onychomycosis, and dermal mycosis diagnoses. additionally, pediatric-onset diabetes participants were significantly more likely to experience localized dermatophytosis of the body (tinea corporis; or 6.49, 3.00-14.02 ci), feet (tinea pedis; or 9.01, 3.40-23.92 ci), and perianal region (or 28.25, 1.46-548.37 ci) than their nondiabetic counterparts. tinea cruris, a dermatophyte infection localized to the groin, was not clearly increased in the pediatriconset diabetes cohort (or 20.12, 0.96419.99 ci). consistent with the findings of a separate study,3 we observed a significant association between pediatric-onset diabetes and candidiasis of urogenital sites (or 12.77, 8.16-19.98 ci). notably, literature suggests that the relationship between pediatric diabetes and vulvovaginal candidiasis may be isolated to postpubescent teenagers, as low estrogen levels during early childhood create a rich, anaerobic flora that inhibits candida sp. growth.4 although participants were randomly selected, our case cohort exhibited female predominance (74%). one potential explanation is that puberty generally begins earlier in females, and physiological insulin resistance during this time gives rise to a higher incidence of t2d in adolescent females over males.5 due to the retrospective nature of this study, a causal relationship between pediatric-onset diabetes and cutaneous fungal infection prevalence cannot be determined. additionally, this study does not investigate glycemic control and correlation to cutaneous fungal infections. however, the findings do suggest that certain cutaneous fungal infections are more likely to occur in adulthood in those with pediatric-onset dm, including in underrepresented research populations. with the increasing incidence of pediatric dm, it will be important for clinicians to monitor the long-term cutaneous complications, including the risk of fungal infections, to improve dermatology patient outcomes. further research is warranted to investigate the role of childhood diabetes intervention and glycemic control in mitigating dermatologic fungal complications through adulthood. conflict of interest disclosures: dr. rajani katta serves on an advisory board for vichy laboratories. emily strouphauer has no conflicts of interest to disclose. skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 878 table 1. demographics of pediatric-onset diabetes cases and corresponding controls in all of us sd, standard deviation characteristic cases controls n 300 1200 average age (sd) 30.0 (7.69) 30.0 (7.69) race/ethnicity (%) asian 1 (0.33) 4 (0.33) black or african american 79 (26.33) 316 (26.33) more than one population 13 (4.33) 52 (4.33) other 92 (30.66) 368 (30.66) white 115 (38.33) 460 (38.33) ethnicity (%) hispanic or latino 94 (31.33) 376 (31.33) not hispanic or latino 195 (65.0) 780 (65.0) other 11 (3.66) 44 (3.66) sex (%) female 222 (74.0) 888 (74.0) male 78 (26.0) 312 (26.0) skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 879 table 2. cutaneous fungal comorbidities of pediatric-onset diabetes cases and corresponding controls in all of us ci, confidence interval; or, odds ratio *denotes significance diagnostic count of fungal infections cases controls or (95% ci) p value candidal intertrigo 0 1 1.331 (0.0541-32.745) 0.8613 candidiasis of urogenital site 74 30 12.770 (8.163-19.977) <0.0001 * candidiasis of mouth 14 7 8.3427 (3.337-20.860) <0.0001 * dermal mycosis 0 1 1.331 (0.0541-32.745) 0.8613 dermatophytosis 48 19 11.840 (6.842-20.488) <0.0001 * dermatophytosis of unspecified region 13 2 27.132 (6.089120.907) <0.0001 * tinea corporis 17 11 6.493 (3.008-14.016) <0.0001 * tinea cruris 2 0 20.1089 (0.963419.988) 0.0529 tinea pedis 13 6 9.014 (3.397-23.919) <0.0001 * tinea of perianal region 3 0 28.2471 (1.455548.369) 0.0273 * onychomycosis due to dermatophyte 24 3 34.696 (10.374116.045) <0.0001 * pityriasis versicolor 7 8 3.560 (1.281-9.896) 0.0149 * superficial mycosis (unspecified) 4 1 16.203 (1.804145.506) 0.0129 * individuals with more than one fungal diagnosis cases controls or (95% ci) p value number of participants (%) 102 (34%) 63 (5.25%) 9.297 (6.562-13.173) <0.0001 * skin july 2023 volume 7 issue 4 (c) 2023 the authors. published by the national society for cutaneous medicine. 880 funding: none corresponding author: emily strouphauer, bsa 1 moursund st houston, tx, 77030 phone: (512)-925-6838 email: emily.strouphauer@bcm.edu references: 1. divers j. trends in incidence of type 1 and type 2 diabetes among youths — selected counties and indian reservations, united states, 2002–2015. mmwr morb mortal wkly rep. 2020;69. doi:10.15585/mmwr.mm6906a3 2. aragon tj. epitools: epidemiology tools. published online 2020. https://cran.rproject.org/package=epitools 3. atabek me, akyürek n, eklioglu bs. frequency of vagınal candida colonization and relationship between metabolic parameters in children with type 1 diabetes mellitus. j pediatr adolesc gynecol. 2013;26(5):257-260. doi:10.1016/j.jpag.2013.03.016 4. banerjee k, curtis e, de san lazaro c, graham jc. low prevalence of genital candidiasis in children. eur j clin microbiol infect dis. 2004;23(9):696-698. doi:10.1007/s10096-004-1189-2 5. temneanu o, trandafir l, purcarea m. type 2 diabetes mellitus in children and adolescents: a relatively new clinical problem within pediatric practice. j med life. 2016;9(3):235-239. skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 284 brief articles extensive primary anetoderma refractory to erbium yag fractionally ablative laser james c. prezzano, md1, christopher t. richardson, md, phd1, glynis a. scott, md1, sherrif f. ibrahim, md, phd1 1dermatology department at the university of rochester medical center, rochester, ny primary anetoderma is a rare elastolytic disorder characterized by well-circumscribed flaccid, atrophic macules and patches caused by focal loss of elastic fibers.1 lesions herniate or bulge with palpation or pressure and are described as having a “saclike” appearance.1 anetoderma is divided into two forms: primary, which is idiopathic and occurs on clinically normal skin, and secondary, which follows a prior dermatosis. primary anetoderma has been described in association with autoimmune conditions such as systemic lupus erythematosus, systemic sclerosis, antiphospholipid antibody syndrome and thyroiditis, as well as in association with hiv.2,3 a 23 year old woman with no significant past medical history presented to the clinic for evaluation of “spots” that gradually appeared over 2-3 years. the lesions erupted without associated redness, itching, scaling, or burning. she stated that the lesions had stabilized over the two years prior to presentation. the patient previously reported a history of mild acne vulgaris in a small area that was involved, though she stated her acne was not extensive. a prior biopsy was consistent with dermal fibrosis consistent with scar. on physical exam, the patient’s trunk and bilateral proximal extremities were covered by innumerable hypopigmented to flesh colored atrophic plaques that herniated with slight palpation (figure 1). the face, neck introduction primary anetoderma is a rare elastolytic disorder characterized by well-circumscribed flaccid, atrophic macules and patches caused by focal loss of elastic fibers. anetoderma is divided into two forms: primary, which is idiopathic and occurs on clinically normal skin, and secondary, which follows a prior dermatosis. although it is indolent, the lesions of anetoderma persist and may be associated with significant aesthetic changes causing potential psychosocial difficulties. anetoderma has been successfully treated with ablative, pulsed dye and nonablative fractionated lasers. patients with secondary anetoderma and anetoderma limited to a relatively small body surface area may be more amenable to laser treatment than patients with extensive involvement. abstract case presentation skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 285 figure 1. hypopigmented to flesh colored atrophic plaques and distal extremities were spared. a test area was chosen to treat with a fractionally ablative erbium yag laser (2940-nm) to a 1 mm depth, density of 11%, with three passes and a clinical end point of pinpoint bleeding. the patient was seen in follow up about three months after treatment with equivocal response (figure 2). a second lesion was treated in fully ablative mode with the er:yag laser, but also did not result in significant improvement. given her lack of response, repeat biopsy was performed at eight months after treatment, which showed superficial and focal loss of elastin, consistent with anetoderma (figure 3). an autoimmune workup including ana, lupus anticoagulant, and antibodies against cardiolipin, beta-2 glycoprotein, thyroglobulin and thyroid peroxidase, as well as comprehensive metabolic panel, complete blood count, thyroid tests, and hiv were performed and were unremarkable. figure 2. equivocal response 3 months after treatment primary anetoderma has historically been subdivided into two subtypes: the jadassohn-pellizzari type, with preceding inflammation, and the schweninger-buzzi type, which appears spontaneously.4 the two types have a similar course so the division is primarily considered academic. the trunk and extremities are the most commonly discussion skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 286 figure 3. superficial and focal loss of elastin (4x), consistent with anetoderma (a) h&e (b) verhoeff-van elastic stain involved sites.4 due to the above associations, primary anetoderma should prompt an autoimmune workup including ana, hiv, and antiphospholipid panel (lupus anticoagulant, anticardiolipin antibody and anti-beta-2-glycoprotein).3 the current case is best classified as idiopathic primary anetoderma of the schweninger-buzzi subtype with no associated autoimmunity markers, thyroid abnormalities or hiv. there are no established treatment recommendations for anetoderma. topical corticosteroids and systemic medications such as hydroxychloroquine have been tried with variable success. several case reports suggest laser therapy may be helpful for anetoderma. a 10,600-nm co2 laser using the pinhole method was used successfully to treat lesions on the ear of an eight-year-old boy with secondary anetoderma following juvenile xanthogranuloma.5 anetoderma secondary to a severe sun burn was successfully treated with 595-nm pulsed-dye laser combined with 1550-nm non-ablative fractionated laser.6 a 10,600-nm co2 laser was used to successfully treat anetoderma secondary to steven-johnson syndrome.7 these cases show promise for energy based treatments for secondary anetoderma. unfortunately, ablative laser treatment was not as successful in our patient with primary anetoderma, likely given the depth and number of lesions. although it is indolent, the lesions of anetoderma persist and may be associated with significant aesthetic changes causing potential psychosocial difficulties. anetoderma has been successfully treated with ablative, pulsed dye and non-ablative fractionated lasers. patients with secondary anetoderma and anetoderma limited to a relatively small body surface area may be more amenable to treatment than patients with extensive involvement. conflict of interest disclosures: none funding: none a b skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 287 corresponding author: james c. prezzano, md university of rochester dermatology at college town 40 celebration drive rochester, ny 14620 phone: 585-275-7546 fax: 585-461-3509 email: james_prezzano@urmc.rochester.edu references: 1. emer j, roberts d, sidhu h, et al. generalized anetoderma after intravenous penicillin therapy for secondary syphillus in a hiv patient. j clin aesthet dermatol. 2003;6:23-28. 2. göebel-pinto jb, de almeida hl jr, de castro las, rocha nm. ultrastructural aspects of primary anetoderma. j cutan pathol. 2017;44:786-789. 3. tong lx, beasley j, meehan s, et al. primary anetoderma with undifferentiated connective tissue disease. dermatol online j. 2017;23. 4. kineston dp, xia y, turiansky gw. anetoderma: a case report and review of the literature. cutis. 2008;81:501-6. 5. lee sm, kim yj, chang se. pinhole carbon dioxide laser treatment of secondary anetoderma associated with juvenile xanthogranuloma. dermatol surg. 2012 oct;38:1741-3. 6. wang k, ross na, saedi n. anetoderma treated with combined 595-nm pulsed-dye laser and 1550-nm non-ablative fractionated laser. j cosmet laser ther. 2016;18:38-40. 7. cho s, jung jy, lee jh. treatment of anetoderma occurring after resolution of stevens-johnson syndrome using an ablative 10,600-nm carbon dioxide fractional laser. dermatol surg. 2012;38:677-9. mailto:james_prezzano@urmc.rochester.edu a 14-day, single-blind, controlled study to assess the qualitative improvement in skin moisturization and desquamation of 15% lactic acid moisturizer with ceramides (lamc) treatment in healthy female subjects zoe diane draelos1, steven b hall2, carey munsick2 1dermatology consulting services, pllc, high point, nc, 2sandoz, inc., princeton, nj synopsis • traditional moisturizers with emollients (dimethicone, cetyl alcohol) improve skin appearance by smoothing down dry scaly skin to temporarily improve skin appearance. the dry scaly skin ultimately must desquamate for overall healthy skin. • topical application of ingredients, such as alpha-hydroxy acids, can facilitate the natural skin desquamation process. lactic acid moisturizer with ceramides (lamc) contains ceramides, humectants and lactic acid that work in combination to moisturize dry skin and induce desquamation. objectives • to investigate if amlactin® rapid relief restoring lotion + ceramides (15% lamc) improves the skin through moisturization and desquamation. • to assess safety by the evaluation of any adverse events reported during the study. methods • this was a randomized, single-center, controlled, evaluatorblinded, within-subject comparison study of lamc versus no treatment in healthy female subjects where subjects served as their own control. • fifty-six female subjects 50+ year of age with dry rough skin on the anterior shins (defined as grade 3-4 on the dermatologist evaluation of the skin; dry skin scale) were enrolled and treated. • all subjects had a template-located target site identified on both anterior shins for the purpose of determining the moisturization and desquamation potential. • the study product was applied to the randomized leg twice daily for 14 days. • evaluation of moisturization and desquamation potential were assessed clinically using sticky tape corneocyte counts (dsquame®) as well as dermatologist evaluation (skin dryness, skin texture/roughness (tactile), skin texture/roughness (visual), desquamation/flakiness, and luminosity/radiance) of the skin at baseline, day 2 and day 14. • additionally, photography of the d-squame® discs and subjects’ shins were captured day 1,2 and 14 results • lamc demonstrated clinically and statistically significant improvement to no treatment in enhanced moisturization and desquamation via d-squames at both day 2 and day 14 (-2.51 and -3.07 on a 5-point scale at p<0.0001, respectively). • treatment success assessed by the investigator (via the dry skin scale) demonstrated statistical significance with lamc, with the majority of p values being <0.0001. • lamc was well tolerated with no reported adverse events over the duration of the study. conclusions • lamc provided a statistically significant and clinically meaningful improvement in moisturization and desquamation as evidenced by d-squame®, dry skin scale, and subject self-assessments in the population studied. • additionally, the product appeared to be safe and well tolerated. references • black d, boyer j lagarde jm. int j of cosmetic sci, 2006;28, 35-44 acknowledgements • we thank jose gallo (sandoz) for his statistical support on this study • we thank christopher oh, sandoz fellow, for his editorial support on this poster disclosures • this study was funded by sandoz, inc., princeton, nj • hall, munsick employees of sandoz inc. amlactin® rapid relief is a registered trademark of sandoz inc. lamc provided significant improvement in moisturization and desquamation by physician assessment on the dry skin scale 0 1 2 3 4 5 dryness roughness (tactile) roughness (visual) flakiness lack of luminosity • improvement in desquamation was associated with significant improvements in all 5 subscales of the dry skin scale as assessed by the physician at day 2 and the end of study (p<0.0001) • lamc was safe and well tolerated —no adverse events —no discontinuations * * * * * * * * * * day bl 2 14 bl 2 14 bl 2 14 bl 2 14 bl 2 14 bl 2 14 bl 2 14 bl 2 14 bl 2 14 bl 2 14 lamc plb (no product)bl=baseline; plb=placebo; sd=standard deviation. *p<0.0001 vs baseline. data on file. sandoz, inc. dry skin scale m e a n ( s d ) lamc provided significant improvement in moisturization and desquamation 1.20 3.80 1.75 4.08 4.27 4.25 0.00 1.00 2.00 3.00 4.00 5.00 6.00 l a m c p l b (n o p ro d u c t) day 1 2 14 1 2 14 d-squame images day 14 shin images -3.07* -0.45 -2.51* -0.16 difference from bl bl=baseline; plb=placebo; sd=standard deviation. *p<0.0001 vs baseline. data on file. sandoz, inc. mean (sd) d-squame quantification results day 1 day 2 day 14 responder rates: • subject satisfaction (age, social confidence, and psychological well-being) appeared to correlate with efficacy as assessed by blinded, independent raters product usage that led to higher degrees of subject satisfaction: maximizing pan-facial aesthetic outcomes: findings and recommendations from the harmonytm study michael kaminer, md1; joel l. cohen, md2; vic narurkar, md3; ava shamban, md4; phil werschler, md5; garrett t. shumate, bs6; conor j. gallagher, phd6 1skincare physicians, inc., chestnut hill, ma, usa; 2aboutskin dermatology and dermsurgery, englewood, co, usa; 3bay area laser institute, san francisco, ca, usa; 4ava md, santa monica, ca, usa; 5university of washington, school of medicine, seattle, wa, usa; 6allergan plc, irvine, ca • highest improvement was achieved with more volume in the zygomaticomalar and less in the anteromedial cheek • more overall volume did not translate into a higher improvement for the patient fall clinical dermatology conference, las vegas, october 12-15, 2017 acknowledgments: this study was funded by allergan plc. medical writing and editorial assistance was provided to the authors by cactus communications, and was funded by allergan plc. all authors met the icmje authorship criteria. neither honoraria nor other form of payments were made for authorship. financial disclosures: m kaminer received consulting fees from cytrellis, soliton, and zeltiq; has ownership in cytrellis and soliton; received honoraria from cutera and soliton; and received funding from allergan, cytrellis, soliton, sciton, cutera, cynosure, galderma, and l’oreal. jl cohen and p werschler serve as investigators for allergan plc. v narurkar received consulting fees from allergan plc, philips, and revance; served on the advisory boards for cabocon aesthetics and clarisonic; has ownership in the cosmetic boot camp llc; and received funding from allergan plc, merz aesthetics, solta medical, myoscience, polyremedy llc, and syneron candela. ava shamban is an investigator for allergan plc, medicis, and galderma; and a consultant for allergan plc and merz. gt shumate and cj gallagher are employees of allergan plc and may own stock or stock options in the company. • aesthetic medicine has evolved from targeting individual treatment areas to a more global approach of facial rejuvenation (i.e. pan-facial treatment). • a multimodal approach to pan-facial aesthetic treatment has not been systematically evaluated in controlled clinical studies. as a result, there is a paucity of universal best practices. • harmonytm was the first clinical trial to evaluate the impact of combined treatment with hyaluronic acid fillers, onabotulinumtoxina, and bimatoprost 0.03% using a range of validated measures • objective: understand the treatment strategies that enabled the clinical sites with the highest improvements on the primary endpoint (face-q satisfaction with face overall) to achieve incrementally greater results, as compared to those sites with the lowest improvements background conclusions study design • data from the clinical sites with the lowest (2 sites) and highest (2 sites) improvements based on the primary endpoint (face-q satisfaction with face overall) were separated to understand “how” the highest improvements were achieved • note that all clinical sites exhibited a significant improvement • a comparative analysis of the treatment characteristics (e.g. product selection, injection location, and injection volume) was performed to understand the factors enabling the highest performing sites to achieve incrementally greater improvements. subjects • evaluation indicated similarity across most of the demographic characteristics: characteristic highest sites lowest sites gender all female all female age (mean) 51.8 years 52 years fitzpatrick skin phototype (mean) 2.9 3.2 • evaluation indicated similar baselines across most of the endpoints: endpoint lowest sites (mean) highest sites (mean) face-q: satisfaction with facial appearance overall 22.7 22.4 face-q: aging appearance appraisal 19.2 18.5 face-q: social confidence scale 22.6 22.1 face-q: psych well-being scale 28.4 27.8 self-perception of age (years) 0.3 0.5 overall mid-face volume deficit 3.0 3.1 nasolabial folds (nlfss) 2.5 2.4 oral commissures (ocss) 2.1 2.1 perioral lines (polss) 1.8 1.9 glabellar line severity at maximum frown (fws) 2.6 2.2 crow’s feet line severity (fws) 2.4 2.3 eyelash prominence (gea) 1.9 1.6 materials and methods results efficacy outcomes voluma xc: midface category lowest sites (mean) highest sites (mean) difference (%) face-q: satisfaction with facial appearance 9.1 13.8 52 face-q: aging appearance appraisal -4.3 -8.7 103 face-q: aging appearance appraisal (visual analog scale) -3.6 -6.1 70 face-q: social confidence scale 4.2 7.3 75 face-q: psych well-being scale 5.1 8.2 60 self-perception of age -3.4 -6.3 89 appearance of periorbital lines -10.4 -14.2 37 global aesthetic improvement (subject) 1.5 1.7 16 global aesthetic improvement (evaluating investigator) 1.1 1.6 55 category lowest sites (mean) highest sites (mean) difference (%) glabellar lines (max frown) -1.70 -1.21 -29 eyelash prominence 1.90 1.47 -22 crow’s feet lines (max smile) -0.88 -1.37 63 midface -1.20 -1.95 62 nasolabial folds -0.90 -1.32 46 perioral lines -0.72 -1.26 75 oral commissures -0.68 -1.32 92 location highest sites mean volume injected per subject (% of subjects treated) lowest sites mean volume injected per subject (% of subjects treated) zygomaticomalar v1, v2 1.3 (100%) 1.0 (90%) anteromedial cheek v3 0.9 (100%) 1.2 (90%) submalar v4 0.9 (53%) 0.7 (75%) overall midface total v1-v4 2.7 (100%) 2.9 (90%) ultra xc & ultra plus xc ultra xc & ultra plus xc layering use of touch-ups location product highest sites mean volume injected per subject (% of subjects treated) lowest sites mean volume injected per subject (% of subjects treated) radial cheek total ultra xc + ultra plus xc 0.0 (0%) 0.8 (30%) ultra xc 0.0 (0%) 0.5 (30%) ultra plus xc 0.0 (0%) 0.7 (15%) perioral region total ultra xc + ultra plus xc 0.8 (79%) 0.6 (55%) ultra xc 0.7 (68%) 0.6 (55%) ultra plus xc 1.0 (16%) 0.3 (15%) overall use total ultra xc + ultra plus xc 4.0 (100%) 3.4 (100%) ultra xc 3.0 (84%) 1.7 (65%) ultra plus xc 2.2 (68%) 2.4 (95%) location product highest sites mean volume injected per subject (% of subjects treated) lowest sites mean volume injected per subject (% of subjects treated) nlf total ultra xc + ultra plus xc 2.0 (89%) 1.2 (95%) ultra xc 2.0 (79%) 0.6 (20%) ultra plus xc 0.7 (32%) 1.1 (90%) oral commissures total ultra xc + ultra plus xc 0.9 (100%) 1.0 (90%) ultra xc 1.0 (40%) 0.5 (65%) ultra plus xc 0.7 (68%) 0.7 (75%) marionette lines total ultra xc + ultra plus xc 1.2 (50%) 1.1 (75%) ultra xc 0.3 (10%) 0.5 (40%) ultra plus xc 1.1 (53%) 0.8 (75%) location highest sites % of sub that rec’d both products (% rec’d both products in same visit) lowest sites % of sub that rec’d both products (% rec’d both products in same visit) nasolabial fold 17.6 (11.8) 15.8 (5.3) marionette lines 20.0 (10.0) 53.3 (53.3) oral commissures 5.3 (0.0) 55.6 (33.3) radial cheek 0.0 (0.0) 50.0 (50.0) perioral 6.7 (0.0) 27.2 (18.2) • highest improvement was achieved when using only one product per location product highest sites mean volume injected per subject (% of subjects treated) lowest sites mean volume injected per subject (% of subjects treated) voluma xc 1.3 (53%) 0.9 (70%) ultra xc 1.8 (58%) 0.9 (35%) ultra plus xc 1.1 (48%) 0.9 (60%) • highest improvement was achieved using more touch-up volume for all fillers scan to obtain pdf of poster • highest sites exhibited greater improvement across all pros • highest sites had less improvement in glabellar lines and eyelash prominence, which could be attributed to baseline differences • highest sites exhibited greater improvement in all other filler and toxin related outcomes category ultra xc ultra plus xc ultra xc + ultra plus xc voluma xc zygomaticomalar anteromedial cheek lower face nlf marionette lines oral commissure radial cheek perioral touch up key: highest sites used more volume highest sites used less volume product preferred by both highest and lowest sites product overlay: • highest improvements were achieved when using only one product per location highest sites lowest sites perceived age perceived age 6.3 years younger 3.4 years younger midface: midface: lower face: lower face: 2.7 ml voluma xc v1 + v2 = 1.3 ml v1 + v2 = 1.0 ml nasolabial folds nasolabial folds marionette lines marionette lines oral commissures oral commissures perioral lines perioral lines v3 = 0.9 ml v3 = 1.2 ml 2.0 ml combined 1.2 ml combined 1.2 ml combined 1.1 ml combined 0.9 ml combined 1.0 ml combined 0.8 ml combined 0.6 ml combined 2.9 ml voluma xc 4.0 ml ultra xc + ultra plus xc 3.4 ml ultra xc + ultra plus xc to obtain a pdf of this poster: scan the qr code or visit www.allergancongressposters.com/516224 charges may apply. no personal information is stored. enter a valid e-mail to send this qr code or click to download. please ensure that qrcode@allergancongressposters.com has been added to your safe senders list or spam filter. fc17posterallergankaminermaximizingpanfacialaestheticoutcomes.pdf tapinarof inhibits the formation, cytokine production, and persistence of resident memory t cells in vitro nathan mooney,1 jessica e. teague,1 ahmed e. gehad,1 kimberly mchale,2 david s. rubenstein,2 rachael a. clark1 1brigham and women’s hospital, boston, ma, usa; 2dermavant sciences, morrisville, nc, usa background ■ tapinarof (vtama®; dermavant sciences, inc.) is a first-in-class, non-steroidal, topical, aryl hydrocarbon receptor (ahr) agonist approved by the food and drug administration for the treatment of plaque psoriasis in adults,1 and under investigation for the treatment of psoriasis in children down to 2 years of age and for atopic dermatitis in adults and children down to 2 years of age ■ tapinarof cream 1% once daily treatment has been observed to induce a remittive effect in the phase 3 psoriasis long-term extension trial, psoaring 32  – patients who achieved physician global assessment (pga) of 0 (clear) after topical tapinarof treatment remained clear for a median of ~4 months after therapy was discontinued, defined as a pga of 0 or 1 (almost clear) while off therapy after achieving complete disease clearance (figure 1)2 ■ resident memory t cells (t rm ) drive lesional recurrence in psoriasis and are affected by ahr signaling3–5 ■ ahr binds to toxins, endogenous and exogenous ligands, and has published effects on t cell differentiation6,7 figure 1. duration of remittive effect among patients entering psoaring 3 with a pga score of 0 (clear): maintenance of a pga score of 0 or 1 (almost clear) while off therapy 0 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 25 50 75 100 125 150 175 200 225 250 275 300 325 79 number of patients at risk overall 76 58 48 44 33 29 23 19 17 17 17 15 trial end p ro b a b il it y o f d is e a se w o rs e n in g time (days) median time to pga ≥2 115 days overall (n=79) pga, physician global assessment. objective ■ to study the effect of tapinarof on t rm using in vitro assays materials and methods t cell activation and cytokine production assessment ■ blood-derived t cells were cultured with anti-cd2/cd3/cd28 activation beads for 1 week – activation was assessed at 24 hours (cd69 expression) – expression of other markers (cd69, cd103, etc.) was determined after 1 week of culture ■ cytokine production was quantified using intracellular cytokine staining and flow cytometry analysis ■ an antigen-presenting cell assay was used to quantify the t rm survival niche in skin cells ■ dermatomed samples of human skin were cultured in th17-skewing conditions8 for 3 days, and analyzed for t cell activation (cd107a) and entry into the cell cycle (ki-67) by immunostaining results suppression of early t cell activation and induction of cd39 expression ■ a significantly lower proportion of tapinarof-treated t cells (both cd4+ and cd8+ cells; p=0.012) were activated compared with control, following treatment for 24 hours (figure 2a) ■ numerically higher proportions of cd4 cells and significantly higher proportions of cd8 cells (p=0.002) expressed cd39 following tapinarof treatment compared with control after 1 week (figure 2b) figure 2. tapinarof significantly suppressed early t cell activation after 24 hours and induced cd39 expression after 1 week of culture co nt ro l ta pi na ro f cd4+ a p=0.012 0 10 20 30 co nt ro l ta pi na ro f cd8+ p=0.012 p=0.002 0 10 20 30 40 a ct iv a te d t c e ll s, % cd 8 + cd 4 + b –75 –50 –25 0 25 c h a n g e , % cd 4 cd 8 0 20 60 40 80 p o si ti v e , % control individual donor/data point tapinarof in vitro generation of t rm ■ cd4 t rm formation was significantly reduced (cd69+, p=0.045 and cd69+cd103+, p=0.027) and there was a trend for reduced cd8 t rm formation with tapinarof compared with control (figure 3) figure 3. tapinarof suppressed cd4 t rm formation in an in vitro culture system co nt ro l ta pi na ro f cd4 t rm a –200 400 200 0 600 cd69+ p=0.045 co nt ro l ta pi na ro f –50 100 50 0 150 cd69+cd103+ cd69+cd103+ p=0.027 c e ll s/ 1 0 0 0 v ia b le , n b –100 0 –50 50 69+ 69+/ 103+ c h a n g e i n n u m b e r o f c d 4 t r m , % co nt ro l ta pi na ro f c –100 200 100 0 300 co nt ro l ta pi na ro f –500 500 0 1000 c e ll s/ 1 0 0 0 v ia b le , n d –100 0 –50 50 c h a n g e i n n u m b e r o f c d 8 t r m , % cd8 t rm cd69+ 69+ 69+/ 103+ control individual donor/data point tapinarof t rm , resident memory t cell. in vitro survival ■ the antigen-presenting cells used il-32β produced by t cells to induce differentiation of monocytes into ox40l/cd40l-expressing dendritic cells (dc), which may support t cell survival in vitro (figure 4a) ■ tapinarof did not inhibit the formation of dc (not shown) but blocked t cell survival, suggesting it may interfere with dc:t cell signaling (figure 4b) figure 4. tapinarof suppressed t cell survival in an in vitro antigen-presenting cell: t cell support assay 2000 4000 6000 8000 10,000 0 14 21 il-32β days in culture monocytes co-stimulatory dc il-32β cd40l cd40lox40l ox40l t cell survival in culture v ia b le t c e ll s, n a b il-32β + dmso control il-32β + tapinarof no il-32β dc, dendritic cells; dmso, dimethyl sulfoxide; il, interleukin. cytokine production by in vitro generated t rm ■ il-17a, tnfα, and ifnγ production was reduced among in vitro generated t rm (figure 5) ■ non t rm : cd69–cd103–; sp t rm : cd69+cd103–; dp t rm : cd69+cd103+ figure 5. tapinarof suppressed cytokine production in cd4 and cd8 t rm cells generated in vitro n on t r m sp t r m dp t r m tapinarofcontrol cd4+ t cellsa 0 20 10 30 il-17a n on t r m sp t r m dp t r m 40 80 90 60 50 70 100 tnfα tnfαc c d 4 t c e ll s, % n on t r m sp t r m dp t r m 0 80 20 40 60 100 tnfα c d 8 t c e ll s, % n on t r m sp t r m dp t r m 0 20 10 30 il-22 n on t r m sp t r m dp t r m 0 40 20 60 ifnα c d 4 t c e ll s, % 0 100 50 150 cd69+ c e ll s, % c d 4 t c e ll s, % c d 4 t c e ll s, % n on t r m sp t r m dp t r m 0 60 20 40 80 ifnα c d 8 t c e ll s, % cd8+ t cellsb sp control sp tapinarof 0 100 50 150 cd69+ cd103+ c e ll s, % dp control dp tapinarof 40 80 70 60 50 90 non t rm p=0.018 c e ll s, % dn control dn tapinarof il-17ad –10 20 10 0 30 cd69+ c e ll s, % sp control sp tapinarof –20 30 20 10 –10 0 40 cd69+ cd103+ c e ll s, % dp control dp tapinarof –2 2 4 6 0 8 non t rm c e ll s, % dn control dn tapinarof dn, double negative; dp, double positive; ifn, interferon; il, interleukin; sp, single positive; t rm , resident memory t cell; tnf, tumor necrosis factor. t rm activation and proliferation ■ tapinarof treatment significantly reduced t rm activation (cd107a; p=0.0024) and proliferation (ki-67; p=0.0067) (figure 6) figure 6. tapinarof suppressed t rm  activation and proliferation in human skin cd107a+ p=0.0024 co nt ro l ta pi na ro f 0 10 40 c d 1 0 7 a + t c e ll s, % ta pi na ro f control individual sample/data point tapinarof 20 30 ki-67+ p=0.0067 co nt ro l 0 5 25 k i6 7 + t c e ll s, % 10 15 20 conclusions ■ our initial results suggest tapinarof: – reduced early activation in cd4+ and cd8+ blood-derived t cells – upregulated cd39 on cd4+ and cd8+ blood-derived t cells – reduced the in vitro generation of cd4+ t rm – reduced il-17a, ifnγ, and tnfα production by cd4+ t rm – reduced t cell survival in an in vitro antigen-presenting cell:t cell support assay – reduced activation and entry into the cell cycle of t rm in healthy skin cultured under th17-skewing conditions ■ additional donors will be tested to confirm statistical significance ■ future studies will also test the effect of tapinarof in vivo using nsg mice grafted with human skin and infused with allogeneic peripheral blood mononuclear cells (pbmcs) ■ the demonstrated effects on t rm may explain the ability of tapinarof to induce a remittive effect in psoriasis clinical trials2 references 1. dermavant sciences. vtama (tapinarof) cream, 1%: us prescribing information. 2022. https://www.vtama.com/ docs/dmvt_vtama_pi.pdf. accessed december 2022. 2. strober b, et al. j am acad dermatol. 2022;87:800– 806. 3. matos tr, et al. j clin invest. 2017;127.11:4031–4041. 4. lefevre ma, et al. curr opin allergy clin immunol. 2021;21:355–360. 5. zaid a, et al. proc natl acad sci u s a. 2014;111:5307–5312. 6. larigot l, et al. biochim open. 2018;7:1–9. 7. quintana fj, et al. nature. 2008;453:65–71. 8. smith sh, et al. j invest dermatol. 2017;137:2110–2119. acknowledgments dermavant science, inc. provided material for these studies under a material transfer agreement. adult skin samples were generously provided by drs. simon g. talbot, shailesh agarwal, and dennis p. orgill of the division of plastic surgery at brigham and women’s hospital, boston, ma. drs. qian zhan and ira kim performed immunostaining and analysis for the activation and proliferation experiment. dr. yoshinori watanabe performed the antigen-presenting cell:t cell survival assays. k.m. and d.s.r. are employees of dermavant science, inc. with stock options. r.a.c. has served as a scientific advisory board member for science immunology, anaptysbio, micreos, and sedec therapeutics. editorial support under the guidance of the authors was provided by apothecom, uk, and was funded by dermavant sciences, inc. in accordance with good publication practice (gpp) guidelines (ann intern med. 2022;175:1298–1304). contact dr kimberly mchale at kimberly.mchale@dermavant.com with questions or comments. acknowledgements: medical writing support was provided by prescott medical communications group (chicago, il) with financial support from ortho dermatologics | presented at the fall clinical dermatology conference • october 17-20, 2019 • las vegas, nv synopsis ◾ halobetasol propionate (hp) and tazarotene (taz) are both effective treatments for psoriasis but are limited by labelling restrictions or potential for adverse events ◾ recently, positive clinical data on a novel halobetasol propionate 0.01%/tazarotene 0.045% (hp/taz; duobriitm) lotion formulation for the treatment of moderate or severe plaque psoriasis have been published1-3 ◾ the unique formulation of hp/taz lotion utilizes a technology that allows uniform disposition of both active ingredients simultaneously onto the skin surface and has been developed to be a non-greasy lotion that would be well-liked by patients, help adherence, and normalize epidermal barrier function objectives ◾ to detail the unique formulation approach to hp/taz lotion development ◾ to assess the absorption and epidermal barrier effects of the novel formulation of hp/taz lotion compared to expected individual results with hp and taz methods polymeric emulsion technology formulation ◾ hp and taz are encapsulated within the same oil droplet together with moisturizing/hydrating excipients (light mineral oil, diethyl sebacate; figure 1) ◾ oil droplets (hp/taz plus excipients) are uniformly distributed within the oil-in-water emulsion; additional water-soluble moisturizing excipients (sorbitol) are trapped within the 3-d matrix (mesh) ◾ on application, the mesh is uniformly distributed on the skin and instantly breaks upon contact with salts commonly present on skin, allowing for uniform absorption of hp/taz figure 1. oil-in-water emulsion droplet separated within a polymeric matrix 1,000x magni�cation 10,000x magni�cation 15,000x magni�cation cryo-scanning electron microscopy other water-soluble excipients are trapped within the polymeric matrix other water-soluble excipients are trapped within the polymeric matrix each oil droplet contains halobetasol and tazarotene plus oil-soluble excipients separated by the three-dimensional matrix. each oil droplet contains halobetasol and tazarotene plus oil-soluble excipients separated by the three-dimensional matrix. percutaneous absorption ◾ percutaneous absorption studies compared the in vitro dermal deposition of hp/taz lotion (polymeric emulsion technology) versus hp 0.05% cream (ultravate®) and taz 0.1% cream (tazorac®) individually • approximately 5 mg/cm2 of each formulation was applied to the epidermis of dermatomated human cadaver back tissue (one donor) • after 24 hours, hp or taz concentrations were determined with liquid chromatography-mass spectrometry ◾ another percutaneous absorption study (same methodology as above) compared the permeability of taz in a layered application of taz 0.1% cream on top of hp 0.05% cream with that of an application of taz 0.1% cream only epidermal barrier function ◾ skin hydration and epidermal barrier maintenance were assessed through corneometry and transepidermal water loss (tewl) over 24 hours in healthy female participants with fitzpatrick skin type i-iv • following a 1-week washout with no moisturizing products, vehicle lotion (0.05 ml) was applied to the volar forearm (other forearm served as control) • moisture (corneometry; corneometer®) and skin barrier function (tewl; tewameter®) were evaluated • patient preference to several features (hydrating, moisturizing, skin absorption, aesthetic) of the vehicle lotion were assessed through a questionnaire (18 questions) at the 8-hour evaluation point results percutaneous absorption ◾ the polymeric emulsion technology used to formulate hp/taz lotion demonstrated higher percutaneous permeation efficiency of active ingredients into the dermal layers than either hp 0.05% cream (figure 2a) or taz 0.1% cream (figure 2b) alone figure 2. dermal levels following 24 hours of topical exposure to halobetasol/ tazarotene lotion versus halobetasol 0.05% cream (a) or tazarotene 0.1% cream (b) 0% 8% 7% 6% 5% 4% 3% 2% 1% 0% 25% 20% 15% 10% 5% hp 0.01%/taz 0.045% lotion halobetasol cream, 0.05% hp 0.01%/taz 0.09% lotion tazarotene cream, 0.1% a. halobetasol dermal levels (n=10) p e rc e n t o f a p p lie d d o se ( m e a n ) epidermis dermis receptor b. tazarotene dermal levels (n=10) hp, halobetasol propionate; taz, tazarotene. ◾ the advantage of simultaneous and uniform delivery of hp/taz using this formulation was apparent when it was shown that simply layering taz 0.1% cream onto hp 0.05% cream decreased the percutaneous permeation of tazarotene (figure 3) figure 3. cumulative receptor phase levels of tazarotene following 24 hours of topical exposure of layered tazarotene 0.1% cream on top of halobetasol 0.05% cream versus tazarotene 0.1% cream alone (n=8) 0% 0.016% 0.014% 0.012% 0.010% 0.008% 0.006% 0.004% 0.002% 0.018% p e rc e n t o f a p p lie d d o se ( m e a n ± s d ) 0 6 12 18 24 time (hours) halobetasol 0.05% cream with tazarotene 0.1% cream in upper layer tazarotene 0.1% cream epidermal barrier function ◾ the vehicle lotion formulation provided rapid and sustained increases in skin moisturization (figure 4) and gradual decreases in tewl over 24 hours (figure 5) figure 4. skin moisturization assessment of vehicle lotion and untreated control over 24 hours using corneometry (n=30) 25 65 60 55 50 45 40 35 30 70 m e a n s co re s ± s d 0 6 12 18 245 11 17 234 10 16 223 9 15 212 8 14 201 7 13 19 time (hours) vehicle lotion untreated control *all time points except baseline p<0.001 versus untreated control. figure 5. skin barrier assessment of vehicle lotion and untreated control over 24 hours using transepidermal water loss (tewl) (n=30) 0 10 5 15 m e a n s co re s ± s d 0 6 12 18 245 11 17 234 10 16 223 9 15 212 8 14 201 7 13 19 time (hours) vehicle lotion untreated control *all time points except baseline p<0.001 versus untreated control. ◾ most participants (93%-100%; 15 total participants) responded favorably (strongly agree or agree) to all questions asked about the various physical attributes (hydrating, moisturizing, skin absorption, aesthetic) of the vehicle lotion conclusions ◾ a fixed combination hp 0.01%/taz 0.045% lotion formulation has been developed that utilizes an innovative polymeric emulsion technology and an optimal selection of solvents, emollients, and humectants which is aesthetically pleasing and provides enhanced barrier to the skin ◾ application of this hp/taz formulation resulted in a higher permeation efficiency of both active ingredients compared with application of hp or taz cream alone ◾ these results are consistent with data from clinical studies, where hp/taz has been shown to provide synergistic activity, with efficacy greater than that which would be predicted from the individual active ingredients3 ◾ taken together, these results suggest that the unique formulation of hp/taz lotion may provide a more effective, predictable, and patient-preferred treatment option than use of separate formulations of hp and taz references 1. gold ls, et al. j am acad dermatol. 2018;79(2):287-293. 2. sugarman jl, et al. j drugs dermatol. 2017;16(3):194-201. 3. kircik lh, et al. j drugs dermatol. 2019;18(3):279-284. author disclosures dr. emil tanghetti has served as speaker for novartis, ortho dermatologics, sun, lilly, galderma, abbvie, and dermira; served as a consultant/clinical studies for hologic, ortho dermatologics, and galderma; and is a stockholder for accure. dr. linda stein gold has served as investigator/consultant or speaker for ortho dermatologics, leo, dermavant, incyte, novartis, abbvie, and lilly. dr. james del rosso has served as a consultant, investigator, and speaker for ortho dermatologics. dr. stefan weiss has served as consultant, speaker, advisor or research honoraria from abbvie, ortho dermatologics, jansen biotech, dermira, almirall, brickell biotech, dermtech, and scynexis. dr. tina lin is an employee of ortho dermatologics. mr. arturo angel and dr. radhakrishnan pillai are employees of bausch health americas inc. optimized formulation for topical application of a fixed combination halobetasol/tazarotene lotion using polymeric emulsion technology emil a tanghetti, md1; linda stein gold, md2; james q del rosso, do3; stefan weiss, md4; tina lin, pharmd5; arturo angel, bs6; radhakrishnan pillai, phd6 1center for dermatology and laser surgery, sacramento, ca; 2henry ford hospital, detroit, mi; 3jdr dermatology research/thomas dermatology, las vegas, nv; 4direct dermatology, palo alto, ca; 5ortho dermatologics, bridgewater, nj; 6bausch health americas, inc, petaluma, ca microsoft word july 2020 covidcon 889 proof returned.docx skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 340 covid concepts virtual continuity clinics: a hybrid approach to longitudinal patient-dermatologist relationships in the wake of covid-19 alexander j. jafari, ba1,2, andrea t. murina, md1 1department of dermatology, tulane university school of medicine, new orleans, la 2tulane university school of public health and tropical medicine, new orleans, la the current coronavirus pandemic (covid-19) caused by the novel sars-cov2 has revolutionized medical practice in the united states. physicians have rapidly adopted telehealth to communicate with their patients and it may remain an important tool for maintaining continuity of care in residency programs. continuity of care, or longitudinal patient-physician interaction, is associated with greater patient satisfaction, including more appropriate follow-up care and fewer missed appointments.1 more patient-physician contact can lead to stronger patient-physician relationships and higher rates of resident satisfaction.1,2 continuity has historically been challenging to achieve in ambulatory graduate medical education (gme) training settings.1 the implementation of virtual continuity clinics in dermatology via telehealth during the covid-19 pandemic may highlight its merits in gme training. resident scheduling and time constraints are the main barriers to maintaining longitudinal care in ambulatory medical specialties. methods to improve continuity in medicine and pediatrics residency programs showed mixed results when using same-day appointments, scheduling to an individual resident or team, and fixed day clinics.1 appropriating a fixed time for virtual continuity clinics allows residents to connect with patients seen in clinic or following discharge from the hospital. virtual continuity visits can be scheduled with the same faculty teams that previously evaluated the patient in-person. while it may be challenging to include all team members from the patient’s initial visit, having the same resident-physician at follow-up can solidify patient-physician rapport. these checkins are opportunities to address patients’ concerns, monitor symptoms, emphasize medication adherence, and assess medication side effects. residents can participate in patient and family education and identify social and environmental barriers to care. teledermatology could be used to connect with abstract the covid-19 crisis has altered the delivery of healthcare due to the rapid utilization of telemedicine. dermatology residency programs may benefit from the use of teledermatology for the purposes of establishing and maintaining continuity over a three-year training program. we examine the current evidence on the effect of continuity on patient and resident satisfaction and elaborate on how teledermatology can help to overcome some of the barriers to longitudinal care. integrating teledermatology into a continuity clinic allows resident physicians to check-in more frequently with patients and provide medication monitoring. we offer suggestions on how programs can integrate teledermatology into a virtual continuity clinic for residents. skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 341 every new patient seen by a resident in clinic, or used to follow up biopsy results during the resident’s scheduled continuity clinic. additionally, any patient starting on a new highrisk medication could be assessed by telehealth within 1-2 weeks of starting the medication. this could decrease patient dosing errors that we commonly see during the use of weekly dosed medications, such as methotrexate. virtual visits provide ease of access, eliminating the need for patients and residents to travel to specific clinics. this would significantly decrease travel time for patients who live in rural areas that lack dermatologic care. virtual or telephone encounters could offer greater access to these underserved patient populations who are at most risk of being lost-to-follow-up due to lack of reliable transportation and limited sick-days.3,4 many of the underserved also lack computers for telemedicine, but in our experience most lowerincome patients do have a cellular phone and can download a telehealth application. continuous care for these vulnerable groups can provide increased access to medical services. in the past, both patients and residents have generally been satisfied with teledermatology.5 while both groups preferred in-person consultations over telemedicine visits, satisfaction with teledermatology still remained high and mainly differed based on the format offered (e.g. store-and-forward versus live-interactive sessions).5 during the current covid-19 pandemic, teledermatology may emerge as a suitable alternative for establishing longitudinal care for patients. the virtual continuity model can be applied to medical specialties that include inpatient and ambulatory care to improve health care transitions. after a patient’s initial visit at the hospital or clinic, he or she can be monitored over time ideally by the same team of physicians who performed the initial in-person evaluation through virtual visits. dermatology program directors can assess residents’ and patients’ experiences with telehealth during the covid-19 pandemic to determine the feasibility of this model downstream. in the wake of covid-19, this hybrid model consisting of both telehealth and office visits may reset the culture of care to support longitudinal interactions between patients and their physicians. conflict of interest disclosures: dr. murina has been a speaker and/or consultant for abbvie, amgen, eli lilly and company, janssen, novartis, ortho-dermatologics. funding: none corresponding author: andrea t. murina, md department of dermatology tulane university school of medicine 1430 tulane ave, #8036 new orleans, la 70112 phone: 504-988-1700 fax: 504-988-1721 email: amurina@tulane.edu references: 1. walker j, payne b, clemans-taylor bl, snyder ed. continuity of care in resident outpatient clinics: a scoping review of the literature. j grad med educ. 2018;10(1):16-25. doi:10.4300/jgme-d-17-00256.1 2. dorrell dn, feldman sr, huang ww-t. the most common causes of burnout among us academic dermatologists based on a survey study. j am acad dermatol. 2019;81(1):269-270. doi:10.1016/j.jaad.2019.01.021 3. wang rf, trinidad j, lawrence j, pootrakul l, forrest la, goist k, levine e, nair s, rizer m, thomas a, wexler r, kaffenberger bh. improved patient access and outcomes with the integration of an econsult program (teledermatology) within a large academic medical center. j am acad dermatol. 2019. doi: https://doi.org/10.1016/ j.jaad.2019.10.053. 4. buster kj, stevens ei, elmets ca. dermatologic health disparities. dermatol clin. 2012;30(1):5359. doi:10.1016/j.det.2011.08.002 5. marchell r, locatis c, burgess g, maisiak r, liu wl, ackerman m. patient and provider satisfaction with teledermatology. telemed j e health. 2017;23(8):684-690. doi:10.1089/tmj.2016.0192 a randomized, double-blind, vehicle-controlled study of the ovicidal efficacy of a new head lice therapy, abametapir lotion, 0.74%, administered for the treatment of head lice infestation scott arnold, md1; sharon hanegraaf2; tiina ahveninen2; hugh alsop2; vernon m bowles, phd3 australian skin cancer clinics, melbourne, australia1; hatchtech pty ltd, melbourne, australia2; university of melbourne, melbourne, australia3 results introduction ¾ successful treatment of head lice infestations may be hampered by limited ovicidal efficacy of current treatments and increasing resistance to commonly used treatments. many current treatments for head lice infestation leave eggs relatively unaffected, typically necessitating a second application after 7 to 10 days to kill newly hatched lice. ¾ abametapir lotion, 0.74% is a novel compound that inhibits enzymes critical for both egg development and survival of crawling lice. objective the objective of this clinical study was to assess the efficacy of abametapir lotion, 0.74% against head louse eggs following a single 10-minute application. methods ¾ this double-blind, randomized, vehicle-controlled, single-dose study enrolled subjects aged ≥ 3 years with an active head lice infestation with both live lice and unhatched eggs. ¾ prior to treatment (day 0), at least 5 viable eggs were removed to serve as a control for untreated hatch rate. either abametapir lotion, 0.74% or vehicle lotion was applied to dry hair for 10 minutes and then rinsed with warm water with no nit combing. ¾ following treatment, the random egg collection process was repeated. eggs deemed viable were incubated for 14 days at 30°c and 60% relative humidity. ovicidal efficacy was measured by comparing the hatch rate of eggs that were collected from the subject’s hair pretreatment and posttreatment and incubated for 14 days. ¾ fifty subjects were randomized to either abametapir lotion, 0.74% or vehicle. ¾ after 14 days of incubation, 100% of eggs from the abametapir lotion, 0.74% group remained unhatched compared with 64% of vehicle-treated eggs (figure 1). ¾ compared with the eggs from the untreated control group, the abametapir lotion, 0.74% group had a 92.9% reduction in hatch rate (95% ci: 86.5-99.4) compared with 42.3% (95% ci: 30.2-54.4) for the vehicle group. the difference in absolute reduction of hatch rates was 50.6% (p<.0001) (table 1). ¾ there were no saes and all teaes were mild except for one rash in the abametapir lotion, 0.74% group that was classified as moderate and resolved by day 4. conclusions ¾ after a single 10-minute application of abametapir lotion, 0.74% inhibited,100% of head lice eggs failed to hatch. ¾ these results in conjunction with data obtained from two pivotal phase 3 studies, demonstrate that abametapir lotion, 0.74% possesses both lousicidal and ovicidal activity following a single application. financial support: this study was supported by hatchtech pty ltd, melbourne, australia. drl publication #782 figure 1. percent unhatched eggs post-treatment and absolute reduction in egg hatch table 1. percent hatched eggs by preand post-treatment and absolute reduction 1. mumcuoglu ky. effective treatment of head louse with pediculicides. j drug dermatol. 2006;5:451-452. 2. durand rs, bouvresse z, berdjane a, et al. insecticide resistance in head lice: clinical, parasitological and genetic aspects. clin midrobiol infect. 2012;18:338-244. references 100.0 92.9 64.0 42.3 0 20 40 60 80 100 120 % eggs unhatched absolute reduction abametapir lotion, 0.74% vehicle lotion *change = post-treatment minus pre-treatment egg hatch status n (%) abametapir lotion, 0.74% (n=25) vehicle lotion (n=25) pre-treatment eggs 119 117 counted as hatched 111 (93.3%) 93 (79.5%) counted as unhatched 8 (6.7%) 24 (20.5%) post-treatment eggs 130 136 counted as hatched 0 49 (36.0%) counted as unhatched 130 (100.0%) 87 (64.0%) hatched eggs % (95% ci) abametapir lotion, 0.74% (n=25) vehicle lotion (n=25) treatment difference p value pre-treatment 93 (82.8, 97.5) 79.4 (69.4, 86.7) 13.9 (3.3, 24.5) post-treatment 0.3 (0.3, 0.4) 37.1 (27.9, 47.3) -36.7 (-46.4, -27.1) change* -92.9 (-99.4, -86.5) -42.3 (-54.4, -30.2) -50.6 (-64.3, -36.9) <.0001 a gee model was applied to account for the correlation of eggs within subject and establish an absolute reduction rate fc17posterpromiusarnoldarandomizeddoubleblind.pdf presented at winter clinical dermatology conference 2020 | hawaii | jan 17–22 2020 long-term safety of certolizumab pegol in plaque psoriasis: pooled analysis over 3 years from three phase 3, randomized, placebo-controlled studies a. blauvelt,1 c. paul,2 p. van de kerkhof,3 r.b warren,4 a. b. gottlieb,5 r. g. langley,6 f. brock,7 c. arendt,8 m. boehnlein,9 m. lebwohl,5 k. reich10,11 1oregon medical research center, portland, or; 2paul sabatier university, toulouse, france; 3radboud university, nijmegen, the netherlands; 4dermatology centre, salford royal nhs foundation trust, manchester nihr biomedical research centre, the university of manchester, uk; 5icahn school of medicine at mount sinai, new york, ny; 6dalhousie university, nova scotia, canada; 7ucb pharma, slough, uk; 8ucb pharma, brussels, belgium; 9ucb pharma, monheim, germany; 10centre for translational research in inflammatory skin diseases, institute for health services research in dermatology and nursing, university medical center hamburg-eppendorf, germany; 11skinflammation® center, hamburg, germany references 1. certolizumab pegol prescribing information. available at www.accessdata.fda.gov /scripts/cder/daf/ index.cfm; 2. certolizumab pegol summary of product characteristics. available at www.ema.europa. eu/ema; 3. blauvelt a et al. jeadv 2019;33(suppl 3):21–2; 4. gisondi p et al. int j mol sci 2017;18:2427. author contributions substantial contributions to study conception/design, or acquisition/analysis/interpretation of data: ab, cp, pvdk, rbw, abg, rgl, fb, ca, mb, ml, kr; drafting of the publication, or revising it critically for important intellectual content: ab, cp, pvdk, rbw, abg, rgl, fb, ca, mb, ml, kr; final approval of the publication: ab, cp, pvdk, rbw, abg, rgl, fb, ca, mb, ml, kr. author disclosures ab: abbvie, aclaris, akros, allergan, almirall, amgen, athenex, boehringer ingelheim, bristol-myers squibb, dermavant, dermira inc., eli lilly, flx bio, forte, galderma, janssen, leo pharma, novartis, ortho, pfizer, regeneron, sandoz, sanofi genzyme, sun pharma, ucb pharma; cp: abbvie, almirall, amgen, boehringer ingelheim, bristol-myers squibb, celgene, dermira inc., eli lilly, gsk, janssen, leo pharma, merck sharp & dohme, novartis, pierre fabre, pfizer, regeneron, sandoz, sanofi genzyme, ucb pharma; pvdk: abbvie, almirall, amgen, bristol-myers squibb, celgene, dermavant, eli lilly, janssen, leo pharma, novartis; rbw: abbvie, almirall, amgen, arena pharmaceuticals, avillion, boehringer ingelheim, celgene, eli lilly, janssen, leo pharma, novartis, pfizer, sanofi, ucb pharma, xenoport; abg: abbvie, allergan, avotres therapeutics, beiersdorf, boehringer ingelheim, bristolmyers squibb, celgene, dermira inc., dr. reddy’s laboratories, eli lilly, incyte, janssen, leo pharma, novartis, sun pharma, ucb pharma, valeant, xbiotech (no personal compensation); rgl: abbvie, amgen, boehringer ingelheim, celgene, centocor, eli lilly, janssen, leo pharma, novartis, pfizer, ucb pharma, valeant; fb, ca, mb: employees of ucb pharma; ml: allergan, aqua, leo pharma, promius; employee of mount sinai which received funds from: abbvie, amgen, boehringer ingelheim, celgene, eli lilly, janssen/johnson & johnson, kadmon, medimmune/astrazeneca, novartis, pfizer, valeant, vidac; kr: abbvie, affibody, amgen, biogen, boehringer ingelheim, celgene, centocor, covagen, forward pharma, gsk, janssen-cilag, kyowa kirin, leo pharma, eli lilly, medac, merck sharp & dohme, novartis, ocean pharma, pfizer, regeneron, samsung bioepis, sanofi, takeda, ucb pharma, valeant, xenoport. acknowledgements the studies were funded by dermira inc. in collaboration with ucb pharma. ucb is the regulatory sponsor of certolizumab pegol in psoriasis. we thank the patients and their caregivers in addition to the investigators and their teams who contributed to these studies. the authors acknowledge susanne wiegratz, ucb pharma, monheim, germany for publication coordination, sarah kavanagh, mph, of ucb pharma, raleigh, nc, usa for statistical analysis, and joe dixon, phd, costello medical, cambridge, uk for medical writing and editorial assistance. all costs associated with development of this poster were funded by ucb pharma. richard warren is supported by the manchester nihr biomedical research centre. objective • to report cumulative three-year safety data from three phase 3 trials of certolizumab pegol in plaque psoriasis. background • certolizumab pegol (czp) is an fc-free, pegylated, anti-tumor necrosis factor (tnf) biologic, which has been approved by the fda and ema for moderate to severe plaque psoriasis (pso).1,2 • czp has shown a safety profile consistent with the anti-tnf class in adults with pso over 96 weeks in phase 3 trials.3 • given that pso is a chronic disease that can require management over much of a patient’s lifetime, it is important to establish the long-term safety profile of treatments.4 • here, we report cumulative safety data, pooled from three czp in pso phase 3 trials over 144 weeks, from a total of 995 patients. methods patients and study design • pooled safety data are presented for patients who received ≥1 dose of czp during the 144 weeks of the cimpasi-1 (nct02326298), cimpasi-2 (nct02326272), or cimpact (nct02346240) phase 3 studies (figure 1). • only 11 placebo-randomized patients continued on placebo after week 16; placebo data are presented to week 16 only. • inclusion criteria: ≥18 years of age with pso for ≥6 months with psoriasis area and severity index (pasi) ≥12, ≥10% body surface area (bsa) affected, physician’s global assessment (pga) ≥3 on a 5-point scale; candidates for systemic pso therapy, phototherapy and/or photochemotherapy. • exclusion criteria: previous treatment with czp or >2 biologics; previous treatment with etanercept (etn) (cimpact only); treatment with etn within the first 12 weeks of enrolment (cimpasi-1 and cimpasi-2 only); history of primary failure to any biologic or secondary failure to >1 biologic; erythrodermic, guttate or generalized pso types; history of or current, chronic or recurrent viral, bacterial or fungal infections. safety assessments • safety data were analyzed for the dose-combined czp-treated group (all czp) and separately for each czp dose. • for patients exposed to both doses of czp over the course of the studies, treatment-emergent adverse events (teaes) were assigned to the dose being received at the time of onset, but each patient was counted in the all czp group only once. • teaes and serious teaes were classified using meddra version 18.1. • serious teaes were defined as those meeting one or more of the following criteria: life-threatening, leading to death, hospitalization, congenital anomalies/birth defects, medically significant (based upon medical judgement), infections requiring intravenous antibiotics, or leading to persistent or significant disability. • incidence rates (ir) were calculated as the number of new cases per 100 patient-years (py). conclusions • no new safety signals were identified compared to previous studies in czp. • the risk of teaes did not increase with longer or higher czp exposure. • the safety profiles of the two czp doses were similar. table 1. pooled demographics and baseline characteristics for patients who received ≥1 dose czp through weeks 0–144 apatients who received both czp 200 mg q2w and czp 400 mg q2w are only included once in the population count for the ‘all czp’ group; bczp 200 mg q2w patients received a loading dose of czp 400 mg at weeks 0, 2, and 4 or weeks 16, 18, and 20. bmi: body mass index; czp: certolizumab pegol; il: interleukin; pasi: psoriasis area severity index; pso: psoriasis; q2w: every two weeks; sd: standard deviation; tnf: tumor necrosis factor. figure 1. cimpasi-1, cimpasi-2, and cimpact study designs dose adjustments were permitted during the open-label periods of all three studies, and were either mandatory or at the discretion of the investigator. data collected during treatment with czp 400 mg q4w in cimpact were summarized under the czp 200 mg q2w treatment group. aloading dose of czp 400 mg q2w at weeks 0, 2 and 4 or weeks 16, 18, and 20. bw: twice per week; czp: certolizumab pegol; etn: etanercept; ld: loading dose; pasi: psoriasis area severity index; q2w: every two weeks; q4w: every four weeks. results patient population • across all three studies, a total of 995 patients received ≥1 dose czp through weeks 0–144. • baseline characteristics were well balanced between the two treatment groups (table 1). incidence of teaes • at week 144, the ir of teaes and serious teaes was comparable between czp dose groups (table 2). • the most common teaes, reported in ≥10% of patients, were nasopharyngitis (ir: 14.2; 95% ci: 12.5, 16.0) and upper respiratory tract infection (ir: 7.9; 95% ci: 6.7, 9.3). • the ir of teaes for czp-treated patients did not increase with longer exposure (table 3). selected teaes and serious teaes of interest • at week 144 the overall incidences of selected teaes of interest and serious teaes of interest were low and were comparable between dose groups (table 4). • there were 7 deaths, 2 of which were assessed by the investigator as related to the study drug (table 2). • the irs of serious infections and malignancies were low, and were comparable between dose groups (table 4). • there was 1 case of active tuberculosis (tb) in a patient who lived in a country with a high tb prevalence (table 4). • there were no reports of serious skin disorders or hypersensitivity reactions, and no cases of lupus or lupus-like events. table 2. overview of teaes in czp-treated patients to week 144 apatients who received both czp 200 mg q2w and czp 400 mg q2w are only included once in the population count for the ‘all czp’ group; bczp 200 mg q2w patients received a loading dose of czp 400 mg at weeks 0, 2, and 4 or weeks 16, 18, and 20; cone case each of acute myocardial infarction, cardiac arrest (due to liver failure and vasodilatory shock in association with hemorrhagic pancreatic necrosis), pneumonia legionella, cirrhosis alcoholic, chronic obstructive pulmonary disease, craniocerebral injury, and multiple injuries, the first two of which were considered related to the study drug by the investigator. ci: confidence interval; czp: certolizumab pegol; ir: incidence rate; py: patient-years; q2w: every two weeks; teae: treatment-emergent adverse event. all czpa (n=995) czp 400 mg q2w (n=728) czp 200 mg q2wb (n=731) baseline demographics and disease characteristics age, years, mean ± sd 45.6 ± 13.2 45.7 ± 13.1 45.3 ± 13.1 male, n (%) 652 (65.5) 472 (64.8) 491 (67.2) bmi, kg/m2, mean ± sd 30.4 ± 7.0 30.6 ± 7.1 30.2 ± 6.7 pso disease duration, years, mean ± sd 18.2 ± 12.5 18.2 ± 12.4 18.4 ± 12.6 pasi, mean ± sd 20.2 ± 7.8 20.2 ± 7.7 20.1 ± 7.8 prior treatments biologic therapy, n (%) 299 (30.1) 220 (30.2) 221 (30.2) anti-tnf 123 (12.4) 88 (12.1) 94 (12.9) anti-il-17 149 (15.0) 106 (14.6) 109 (14.9) anti-il-12/il-23 49 (4.9) 43 (5.9) 30 (4.1) systemic therapy for pso, n (%) 714 (71.8) 532 (73.1) 529 (72.4) all czpa (n=995) czp 400 mg q2w (n=728) czp 200 mg q2wb (n=731) total exposure, py 2,231 1,020 1,211 n (%) ir (95% ci) n (%) ir (95% ci) n (%) ir (95% ci) total teaes 847 (85.1) 144.9 (135.3, 155.0) 563 (77.3) 158.3 (145.5, 171.9) 557 (76.2) 134.1 (123.2, 145.7) total serious teaes 154 (15.5) 7.5 (6.4, 8.8) 82 (11.3) 8.7 (6.9, 10.8) 76 (10.4) 6.7 (5.2, 8.3) teaes leading to discontinuation 88 (8.8) 4.0 (3.2, 4.9) 48 (6.6) 4.7 (3.5, 6.3) 41 (5.6) 3.4 (2.5, 4.6) severe teaes 132 (13.3) 6.3 (5.3, 7.5) 70 (9.6) 7.2 (5.6, 9.1) 66 (9.0) 5.7 (4.4, 7.2) teaes leading to death 7 (0.7)c 0.3 (0.1, 0.7) 3 (0.4) 0.3 (0.1, 0.9) 4 (0.5) 0.3 (0.1, 0.9) a) cimpasi-1 and cimpasi-2 b) cimpact table 3. cumulative teaes over time at weeks 16, 48, 96, and 144 apatients who received both czp 200 mg q2w and czp 400 mg q2w are only included once in the population count for the ‘all czp’ group; bczp 200 mg q2w patients received a loading dose of czp 400 mg at weeks 0, 2, and 4 or weeks 16, 18, and 20. czp: certolizumab pegol; ir: incidence rate; py: patient-years; q2w: every two weeks; teae: treatment-emergent adverse event. all czpa czp 400 mg q2w czp 200 mg q2wb placebo week 16 exposure, py n/n (%) ir (95% ci) 211 414/692 (59.8) 319.1 (289.1, 351.4) 105 217/342 (63.5) 348.3 (303.5, 397.9) 107 197/350 (56.3) 292.1 (252.8, 335.9) 47 97/157 (61.8) 342.6 (277.8, 417.9) week 48 exposure, py n/n (%) ir (95% ci) 729 709/962 (73.7) 219.6 (203.7, 236.4) 418 444/627 (70.8) 228.6 (207.8, 250.9) 311 321/460 (69.8) 221.2 (197.6, 246.7) – week 96 exposure, py n/n (%) ir (95% ci) 1,471 820/995 (82.4) 172.7 (161.1, 184.9) 700 528/711 (74.3) 186.4 (170.9, 203.0) 772 514/726 (70.8) 161.4 (147.8, 176.0) – week 144 exposure, py n/n (%) ir (95% ci) 2,231 847/995 (85.1) 144.9 (135.3, 155.0) 1,020 563/728 (77.3) 158.3 (145.5, 171.9) 1,211 557/731 (76.2) 134.1 (123.2, 145.7) – table 4. selected teaes and serious teaes of interest apatients who received both czp 200 mg q2w and czp 400 mg q2w are only included once in the population count for the ‘all czp’ group; bczp 200 mg q2w patients received a loading dose of czp 400 mg at weeks 0, 2, and 4 or weeks 16, 18, and 20; cinclusive of fatal and non-fatal myocardial infarction, serious cerebrovascular events and congestive heart failure (regardless of seriousness); dpatient with negative quantiferon tb gold test and normal chest x-ray before study entry who was randomized to etn, entered czp 400 mg q2w escape arm at week 16, and was diagnosed 60 days after czp initiation and discontinued the study; eone case of primary progressive multiple sclerosis (medical history indicated that symptoms pre-dated study entry); fone case of multiple sclerosis; gincludes one each of heart failure, congestive heart failure, acute coronary syndrome, extradural hematoma; hincludes one each of acute myocardial infarction, angina pectoris and cerebrovascular accident, and two transient ischemic attack; iincludes one each of adenocarcinoma of colon, anaplastic oligodendroglioma, prostate cancer, clear cell renal cell carcinoma; jincludes one each of breast cancer, glioblastoma, hodgkin’s disease, laryngeal cancer, non-small cell lung cancer, oropharyngeal squamous cell carcinoma, prostate cancer; kincludes three basal cell carcinomas and one keratoacanthoma; lone basal cell carcinoma. ci: confidence interval; czp: certolizumab pegol; etn: etanercept; ir: incidence rate; nmsc: non-melanoma skin cancer; py: patient-years; q2w: every two weeks; teae: treatment-emergent adverse event. all czpa (n=995) czp 400 mg q2w (n=728) czp 200 mg q2wb (n=731) total exposure, py 2,231 1,020 1,211 n (%) ir (95% ci) n (%) ir (95% ci) n (%) ir (95% ci) serious infections 32 (3.2) 1.5 (1.0, 2.1) 16 (2.2) 1.6 (0.9, 2.6) 16 (2.2) 1.3 (0.8, 2.2) active tuberculosis 1 (0.1) 0.0 (0.0, 0.3) 1 (0.1)d 0.1 (0.0, 0.6) 0 (0.0) 0 (0.0, 0.0) demyelinating-like disorders 2 (0.2) 0.1 (0.0, 0.3) 1 (0.1)e 0.1 (0.0, 0.6) 1 (0.1)f 0.1 (0.0, 0.5) major adverse cardiac events (mace)c 9 (0.9) 0.4 (0.2, 0.8) 4 (0.5)g 0.4 (0.1, 1.0) 5 (0.7)h 0.4 (0.1, 1.0) congestive heart failure 1 (0.1) 0.0 (0.0, 0.3) 1 (0.1) 0.1 (0.0, 0.6) 0 (0.0) 0 (0.0, 0.0) all malignancies 14 (1.4) 0.6 (0.3, 1.1) 8 (1.1) 0.8 (0.3, 1.6) 8 (1.1) 0.7 (0.3, 1.3) malignancies excluding nmsc 10 (1.0) 0.5 (0.2, 0.8) 4 (0.5)i 0.4 (0.1, 1.0) 7 (1.0)j 0.6 (0.2, 1.2) nmsc 5 (0.5) 0.2 (0.1, 0.5) 4 (0.5)k 0.4 (0.1, 1.0) 1 (0.1)l 0.1 (0.0, 0.5) 0 16 484032week initial treatment period (double-blinded) <pasi 50 – withdrawn lda czp 200 mg q2w czp 400 mg q2w 14496 open-label treatment placebo q2w <pasi 50 – withdrawn <pasi 50 entered escape arm (czp 400 mg q2w) lda <pasi 50 – withdrawn ≥pasi 50, <pasi 75 czp 200 mg q2w czp 400 mg q2w ≥pasi 50 1: 2 :2 ra n d o m iz a ti o n maintenance period (double-blinded) ≥pasi 50 ≥pasi 50 open-label dose switching lda re-randomization initial treatment period (double-blinded) maintenance period (double-blinded) <pasi 75 <pasi 50 – open-label treatment <pasi 75 <pasi 75 <pasi 75 placebo q2w czp 400 mg q4wetn 50 mg bw washout lda czp 200 mg q2w czp 400 mg q2w czp 400 mg q2w czp 200 mg q2w placebo q2w <pasi 75 entered escape arm (czp 400 mg q2w) 1: 3 :3 :3 ra n d o m iz a ti o n 12 lda czp 400 mg q2w czp 200 mg q2w ≥pasi 50 <pasi 50 open-label treatment 96 1440 16 484032week open-label dose switching presented at fall clinical dermatology conference 2019 | las vegas, nv, usa | 17–20 october, 2019 previously presented at 28th eadv congress 2019 study assessments and statistical analyses • the proportions of patients achieving 75% or 90% improvement from baseline in pasi (pasi 75/pasi 90) and dermatology life quality index (dlqi) 0/1 through 128 weeks of treatment with czp 400 mg q2w (weeks 16–144 of the study) are reported. • responder rates in the subset of patients who achieved a pasi 75 response following 16 weeks of treatment with czp 400 mg q2w in the escape arm are also reported. • estimates of responder rate reflect the simple average response across the multiply imputed data sets, with missing data imputed using markov chain monte carlo (mcmc) methodology. results patient demographics and baseline characteristics • 72 patients did not achieve pasi 50 after 16 weeks of placebo treatment, and entered the czp 400 mg q2w open-label escape arm. patient baseline characteristics are shown in table 1. response to czp treatment • following 16 weeks of treatment with czp 400 mg q2w, 77.2% of patients achieved pasi 75 and 50.2% achieved pasi 90 (figure 2a). • responder rates were maintained over 128 weeks of treatment with czp 400 mg q2w, demonstrating long-term efficacy (figure 2a). • similar trends were reported for dlqi 0/1 (figure 2b). maintenance of response • of patients who achieved pasi 75 after 16 weeks of treatment with czp 400 mg q2w: – the majority (83.9%) maintained pasi 75 over 128 weeks of czp 400 mg q2w treatment (figure 3); – two thirds (66.0%) also reached pasi 90 after 16 weeks of treatment, which increased to 69.6% over 128 weeks (figure 3); – 58.5% also reported dlqi 0/1 remission at week 16, which increased to 75.5% over 128 weeks (figure 3). background • plaque psoriasis (pso) is an immune-mediated, inflammatory disease that affects around 2−4% of adults.1 • certolizumab pegol (czp) is a unique, fc-free, pegylated anti-tumor necrosis factor (tnf) approved by the fda and ema for the treatment of moderate to severe pso.2,3 • in phase 3 trials, patients with moderate to severe pso have demonstrated a durable response to czp over one year (48 weeks) of double-blind treatment.4 • here, we report the long-term clinical responses for patients with pso who received open-label treatment with czp dosed at 400 mg every two weeks (q2w) for up to 128 weeks. methods study design • data were pooled from two phase 3 trials: cimpasi-1 (nct02326298) and cimpasi-2 (nct02326272). full study designs have been reported previously.4 • at week 0, patients were randomized 2:2:1 to czp 400 mg q2w, czp 200 mg q2w (czp 400 mg loading dose at weeks 0, 2 and 4), or placebo. • this analysis only includes patients who: – were randomized to placebo at week 0 – did not achieve a 50% improvement from baseline in psoriasis area and severity index (pasi 50) at week 16 – entered the open-label escape arm where they received czp 400 mg q2w for up to 128 weeks (figure 1). • dosing adjustment was permitted from week 48 of the study based on pasi response and the investigator’s discretion. • patients who did not achieve pasi 50 at any visit after receiving unblinded czp 400 mg q2w for 16 weeks were withdrawn from the study. patients • ≥18 years of age with moderate to severe pso for ≥6 months, defined by pasi ≥12, ≥10% body surface area affected, and physician’s global assessment ≥3 on a 5-point scale. • candidates for systemic pso therapy, phototherapy and/or photochemotherapy. • exclusion criteria: previous treatment with czp or >2 biologics; history of primary failure to any biologic or secondary failure to >1 biologic; erythrodermic, guttate or generalized pso types; current or history of chronic or recurrent viral, bacterial or fungal infections. references 1. parisi r. et al. j invest dermatol 2013;133:377–85; 2. certolizumab pegol prescribing information. available at http://www.accessdata.fda.gov; 3. certolizumab pegol summary of product characteristics. available at http://www.ema.europa.eu/ema; 4. gottlieb ab. et al. jaad 2018;79:302–14.e6; 5. choi j. et al. jaad 2003;49:s57–61; 6. tada y. et al. j dermatol 2019;46:466−477. author contributions substantial contributions to study conception/design, or acquisition/analysis/interpretation of data: kg, rbw, abg, ab, dt, cl, yp, mb, sk, ca, kr; drafting of the publication, or revising it critically for important intellectual content: kg, rbw, abg, ab, dt, cl, yp, mb, sk, ca, kr; final approval of the publication: kg, rbw, abg, ab, dt, cl, yp, mb, sk, ca, kr. author disclosures kg: honoraria and or research support from: abbvie, almirall, amgen, boehringer ingelheim, bristolmyers squibb, celgene, dermira inc., eli lilly, janssen, novartis, pfizer, sun pharma, and ucb pharma. rbw: grants and/or honoraria from abbvie, almirall, amgen, boehringer ingelheim, celgene, janssen, eli lilly, leo pharma, novartis, pfizer, sanofi, ucb pharma, xenoport. abg: research/educational grants: janssen, incyte, eli lilly, novartis, allergan and leo pharma. current consulting/advisory board agreements/speakers bureau: janssen; celgene, bristol-myers squibb, beiersdorf, abbvie, ucb pharma, novartis, incyte, eli lilly, dr. reddy's laboratories, valeant, dermira inc., allergan, sun pharma, sienna pharma. ab: consulting honoraria and clinical investigator: abbvie; aclaris; almirall; amgen; boehringer ingelheim; celgene; dermavant; dermira inc.; eli lilly; genentech/roche; gsk; janssen; leo pharma; meiji; merck; novartis; pfizer; purdue pharma, regeneron, sandoz, sanofi genzyme, sienna pharma, sun pharma, ucb pharma, valeant, vidac. speaker’s fees: eli lilly, janssen, regeneron, sanofi genzyme. dt: research grants from celgene and novartis; honoraria for participation on ad boards, and speaker/ consultancy fees for abbvie, almiral, amgen, boehringer ingelheim, celgene, dignity, dr. reddy's laboratories, galapagos, gsk, janssen, leo, morphosis, msd, eli lilly, novartis, pfizer, sandoz-hexal, pfizer, regeneron/sanofi, ucb pharma; cl: speaker (honoraria) for abbvie; celgene; novartis; eli lilly. investigator for actavis; abbvie; amgen; boehringer ingelheim; celgene; coherus; corrona; dermira inc; eli lilly; galderma; glenmark; janssen; leo pharma; merck; novartis; novella; pfizer; sandoz; stiefel; wyeth. consulting and advisory board honoraria for abbvie; amgen; boehringer ingelheim; dermira inc.; eli lilly; janssen; leo pharma; pfizer; sandoz; ucb pharma; vitae; yp: speaker (honoraria) from: abbvie; celgene; janssen; eli lilly; leo pharma; novartis; regeneron sanofi genzyme. investigator (research grants) from abbvie; baxter; boehringer ingelheim pharma; celgene; centocor/janssen; eli lilly; emd serono; gsk; leo pharma; medimmune; merck; novartis; pfizer; regeneron; takeda; ucb pharma. mb, ca: employees of ucb pharma; sk: employee of ucb pharma; consulting fees from avexis, colorado prevention center, diamedica, puretech, ucb pharma, zosano; kr: advisor and/or paid speaker for and/or participated in clinical trials sponsored by: abbvie, affibody, amgen, biogen, boehringer ingelheim, celgene, centocor, covagen, forward pharma, gsk, janssen-cilag, kyowa kirin, leo pharma, eli lilly, medac, merck sharp & dohme, novartis, ocean pharma, pfizer, regeneron, samsung biopepis, sanofi, takeda, ucb pharma, valeant, xenoport. acknowledgements the studies were funded by dermira inc. in collaboration with ucb pharma. ucb is the regulatory sponsor of certolizumab pegol in psoriasis. we thank the patients and their caregivers in addition to the investigators and their teams who contributed to this study. the authors acknowledge bartosz łukowski, msc, ucb pharma, brussels, belgium, for publication coordination and sophie caseby, msc, costello medical, cambridge, uk for medical writing and editorial assistance. all costs associated with development of this poster were funded by ucb pharma. conclusions • these data demonstrate durable, long-term efficacy of czp 400 mg q2w in patients with moderate to severe pso. • the response of patients who achieved pasi 75 after 16 weeks of czp treatment was maintained over 128 weeks of treatment; pasi 90 and dlqi 0/1 responder rates were also maintained in these patients. objective • to report long-term clinical responses for patients with plaque psoriasis who received treatment with 400 mg certolizumab pegol every two weeks for up to 128 weeks. long-term efficacy of certolizumab pegol dosed at 400 mg every two weeks in patients with plaque psoriasis: pooled 128-week data from two phase 3 trials (cimpasi-1 and cimpasi-2) k. gordon,1 r. b. warren,2 a. b. gottlieb,3 a. blauvelt,4 d. thaçi,5 c. leonardi,6 y. poulin,7 m. boehnlein,8 s. kavanagh,9 c. arendt,10 k. reich11 1department of dermatology, medical college of wisconsin, milwaukee, wi, usa; 2dermatology centre, salford royal nhs foundation trust, manchester nihr biomedical research centre, the university of manchester, uk; 3department of dermatology, icahn school of medicine at mount sinai, new york, ny, usa; 4oregon medical research center, portland, or, usa; 5institute and comprehensive center for inflammation medicine, university hospital of lübeck, lübeck, germany; 6central dermatology and saint louis university school of medicine, st louis, mo, usa; 7centre de recherche dermatologique du québec métropolitain, québec, canada; 8ucb pharma, monheim, germany; 9ucb pharma, raleigh, nc, usa; 10ucb pharma, brussels, belgium; 11translational research in inflammatory skin diseases, institute for health services research in dermatology and nursing, university medical center hamburg-eppendorf, germany; skinflammation® center, hamburg, dermatologikum berlin, berlin, germany figure 1. treatment arms of cimpasi-1 and cimpasi-2 table 1. demographics and baseline characteristics figure 2. response over 128 weeks of treatment with czp 400 mg q2w a) pasi 75 and pasi 90 response (n=72) b) dlqi 0/1 response (n=72) adosing adjustment permitted: in patients who achieved pasi 75 at week 48, dose could be decreased to 200 mg q2w at the investigator’s discretion, thereafter dosing adjustment permitted to week 144 based on pasi response and investigator’s discretion (dose adjusters n=22, non-adjusters n=50). czp: certolizumab pegol; ld: loading dose of czp 400 mg q2w at weeks 0/2/4; pasi: psoriasis area and severity index; pga: physician’s global assessment; q2w: every two weeks. an=70 for dlqi total score at baseline. bmi: body mass index; bsa: body surface area; czp: certolizumab pegol; dlqi: dermatology life quality index; pasi: psoriasis area and severity index; pga: physician’s global assessment; pso: psoriasis; sd: standard deviation; tnf: tumor necrosis factor. estimates of responder rate reflect the simple average response across the multiply imputed data sets, with missing data imputed using markov chain monte carlo (mcmc) methodology. aweek 16 of treatment with czp as shown is equivalent to week 32 of the whole study. dosing adjustment was permitted from week 32 of treatment based on pasi response and the investigator’s discretion; this analysis includes both adjusters and non-adjusters. czp: certolizumab pegol; dlqi 0/1: dermatology life quality index 0/1; mcmc: markov chain monte carlo; pasi 75/90: ≥75/90% improvement from baseline in psoriasis area and severity index; q2w: every two weeks. figure 3. maintenance of response in patients who achieved pasi 75 following 16 weeks of treatment with czp 400 mg q2w estimates of responder rate reflect the simple average response across the multiply imputed data sets, with missing data imputed using markov chain monte carlo (mcmc) methodology. aweek 0 of treatment with czp as shown is equivalent to week 16 of the whole study. dosing adjustment was permitted through weeks 32–116 of treatment based on pasi response and the investigator’s discretion; this analysis includes both adjusters and non-adjusters. czp: certolizumab pegol; dlqi 0/1: dermatology life quality index 0/1; mcmc: markov chain monte carlo; pasi 75/90: ≥75/90% improvement from baseline in psoriasis area and severity index; q2w: every two weeks. pasi 75, pasi 90 and dlqi 0/1 response (n=53) czp 400 mg q2w open-label escape (n=72) age, years, mean (sd) 46.7 (13.1) male, n (%) 48 (66.7) bmi, kg/m2, mean (sd) 31.1 (7.2) prior biologic use, n (%) 23 (31.9) anti-tnf 14 (19.4) pso duration, years, mean (sd) 16.9 (11.9) pasi, mean (sd) 18.3 (6.3) bsa affected, %, mean (sd) 22.4 (13.8) pga score, n (%) 3 (moderate) 53 (73.6) 4 (severe) 19 (26.4) dlqi total score, mean (sd)a 12.9 (7.4) 0 16 32 40 48 144 open-label escape arm:a czp 400 mg q2w (n=72) maintenance period initial treatment period (double blind) open-label treatment <pasi 50 withdrawn <pasi 50 screening 1:2:2 week placebo q2w ≥pasi 75 responders ld czp 200 mg q2w (n=186) czp 400 mg q2w (n=175) czp 200 mg q2w czp 400 mg q2w randomization ≥pasi 50 ≥pasi 50 ≥pasi 50 96 57.8 80 0 4840322480 128 weeks of treatment with czp 400 mg q2wa r e sp o n d e r ra te ( % ) 60 40 100 20 56 10 30 50 70 90 16 10496888064 11272 120 75.5 pasi 75 pasi 90 patients escaped to czp 400 mg q2w after 16 weeks in placebo treatment arm 77.2 50.2 patients escaped to czp 400 mg q2w after 16 weeks in placebo treatment arm 80 0 4840322480 128 weeks of treatment with czp 400 mg q2wa r e sp o n d e r ra te ( % ) 60 40 100 20 56 10 30 50 70 90 16 10496888064 11272 120 68.0 dlqi 0/1 50.0 patients escaped to czp 400 mg q2w after 16 weeks in placebo treatment arm 80 0 48403224 128 weeks of treatment with czp 400 mg q2wa r e sp o n d e r ra te ( % ) 60 40 100 20 56 10 30 50 70 90 16 10496888064 11272 120 83.9 69.6 pasi 75 pasi 90 100.0 dlqi 0/1 75.566.0 58.5 acknowledgements: medical writing support was provided by prescott medical communications group (chicago, il) with financial support from ortho dermatologics; ortho dermatologics is a division of bausch health us, llc presented at winter clinical dermatology conference 2020 • january 17-22, 2020 • kohala coast, hi synopsis ◾ psoriasis is a chronic, immune-mediated disease that can have frequent exacerbations and remissions1 ◾ psoriasis can also negatively impact patients’ lives, particularly in female patients who have reported higher levels of stigmatization, stress, unhappiness, and loneliness compared with males2 ◾ topical corticosteroids are the mainstay of psoriasis treatment, particularly for mild disease,3 while systemic therapies may be useful in patients with severe disease; however, topical treatments are having an increasing role in moderate-to-severe psoriasis as an integral part of combination therapy ◾ recent phase 3 clinical data demonstrated the efficacy and tolerability of a fixed combination lotion containing halobetasol propionate (hp) 0.01% lotion (bryhali® ortho dermatologics, bridgewater, nj) in patients with moderate-to-severe plaque psoriasis4,5 objective ◾ to evaluate the efficacy, safety, and tolerability of hp 0.01% lotion in female and male patients with moderate-to-severe plaque psoriasis methods ◾ in two phase 3, multicenter, double-blind studies, patients were randomized 2:1 to receive hp 0.01% or vehicle lotion once-daily for 8 weeks, with a 4-week posttreatment follow-up4,5 • at baseline, patients were required to have an investigator global assessment (iga) score of 3 or 4 (5-point scale; 0=clear and 4=severe) and affected body surface area (bsa) of 3% to 12% • in these studies, cerave® hydrating cleanser and cerave® moisturizing lotion (l’oreal, ny) were provided as needed for optimal moisturization/cleaning of the skin ◾ data from these two studies were pooled and analyzed post hoc in female and male participants ◾ efficacy assessments included treatment success (≥2-grade improvement from baseline in iga score and score of ‘clear’ or ‘almost clear’ [primary endpoint]), impact on individual signs of psoriasis at the target lesion, and change in bsa affected ◾ treatment-emergent adverse events (teaes) were evaluated results ◾ this analysis included 177 female participants (hp lotion, n=113; vehicle, n=64) and 253 male participants (hp lotion, n=172; vehicle, n=81) ◾ by week 8, significantly more females and males achieved treatment success following treatment with hp 0.01% lotion versus vehicle; significant differences versus vehicle were observed as early as week 2 for females and week 4 for males (figure 1) efficacy and safety of halobetasol propionate 0.01% lotion in the treatment of females with moderate-to-severe plaque psoriasis: post hoc analysis of two phase 3 randomized controlled trials figure 3. mean percent reduction in overall affected body surface area (bsa) by study visit in female and male participants (itt population, pooled) 0% 10% 20% -10% -20% -30% -40% -50% 0 2 4 6 8 12 0% 10% 20% -10% -20% -30% -40% -50% 0 2 4 6 8 12 p e rc e n t c h a n g e f ro m b a se li n e female participants treatment posttreatment -8.2% -17.7% -28.6% -5.6% -27.2% 2.1% -3.9% -8.6% -35.6% -4.6% p e rc e n t c h a n g e f ro m b a se li n e male participants treatment posttreatment -0.1% -15.0% -24.0% -26.8% -6.9% -4.2% -0.7% 1.1% -6.7% -34.9% study visit (weeks) hp lotion (n=113) vehicle (n=64) study visit (weeks) hp lotion (n=172) vehicle (n=81) **p≤0.01 vs vehicle; ***p<0.001 vs vehicle. hp, halobetasol propionate 0.01%; itt, intent‑to‑treat. ◾ all treatment-related teaes with hp lotion through week 8 were reported at the application site: discoloration (n=1 female), infection (n=1 male), dermatitis (n=2 males), and pruritus (n=1 male) conclusions ◾ halobetasol propionate 0.01% lotion was associated with significant, rapid, and sustained reductions in disease severity in female as well as male patients with moderate-to-severe psoriasis, with good tolerability and safety over 8 weeks of once-daily use references 1. nestle fo, et al. n engl j med. 2009;361(5):496‑509. 2. gottlieb ab, et al. int j womens dermatol. 2019;5(3):141‑150. 3. menter a, et al. j am acad dermatol. 2009;60(4):643‑659. 4. sugarman jl, et al. cutis. 2019;103(2):11‑116. 5. green lj, et al. j drugs dermatol. 2018;17(10):1062‑1069. author disclosures dr. fran cook‑bolden has served as a consultant, speaker, and/or investigator for galderma, leo pharma, almirall, cassiopea, and ortho dermatologics, and investigator for encore, foamix, hovione, aclaris, and cutanea. dr. jennifer soung has received honoraria and/or research grants (speaker’s bureau involvement, consultant, investigator, advisory board participant) for celgene, amgen, eli lilly, abbvie, pfizer, allergan, galderma, actavis, ortho dermatologics, actelion, cassiopeia, gsk, national psoriasis foundation (non‑profit), leo, boeringher ingelheim, novartis, kadmon, novan, regeneron, dr. reddy, ucb, janssen, kyowa kirin, menlo, dermira. dr. scott t guenthner has served as a speaker for abbvie, pfizer, allergan, dermira, aclaris, encore dermatology, johnson and johnson, and janssen pharmaceuticals. drs. brock bumpass and tina lin are employees of ortho dermatologics and may hold stock and/or stock options in its parent company. figure 1. overall treatment successa by study visit in female and male participants (itt population, pooled) 50% 60% 70% 40% 30% 20% 10% 0% 0 2 4 6 8 12 50% 60% 70% 40% 30% 20% 10% 0% 0 2 4 6 8 12 p e rc e n ta g e o f f e m a le p a rt ic ip a n ts female participants treatment posttreatment 8.1% 22.4% 33.0% 22.0% 9.9% 0% 1.6% 8.2% 14.6% 42.7% p e rc e n ta g e o f m a le p a rt ic ip a n ts male participants treatment posttreatment 4.7% 17.7% 26.4% 20.7% 6.4% 0% 1.4% 4.7% 6.4% 34.0% study visit (weeks) hp lotion (n=113) vehicle (n=64) study visit (weeks) hp lotion (n=172) vehicle (n=81) *p<0.05 vs vehicle; **p<0.01 vs vehicle; ***p<0.001 vs vehicle. atreatment success is defined as a ≥2‑grade improvement from baseline in iga score and a score of ‘clear’ or ‘almost clear’ (0 or 1). hp, halobetasol propionate 0.01%; iga, investigator global assessment; itt, intent‑to‑treat. ◾ psoriasis signs were also reduced by week 8, with more hp-treated females and males achieving ≥2-grade improvement in erythema, plaque elevation, and scaling compared with vehicle (figure 2) figure 2. treatment successa in psoriasis signs at week 8 in female and male participants (itt population, pooled) 80% 60% 40% 20% 0% 80% 60% 40% 20% 0% 55.0% 19.6% erythema 59.9% 24.7% plaque elevation 57.5% 22.7% scaling hp lotion (n=113) vehicle (n=64) p e rc e n ta g e o f f e m a le p a rt ic ip a n ts female participants 49.2% 16.5% erythema 56.2% 22.7% plaque elevation 60.0% 22.9% scaling hp lotion (n=172) vehicle (n=81) p e rc e n ta g e o f m a le p a rt ic ip a n ts male participants ***p<0.001 vs vehicle. atreatment success is defined as a ≥2‑grade improvement from baseline in each individual sign of psoriasis at the target lesion. hp, halobetasol propionate 0.01%; itt, intent‑to‑treat. ◾ females and males treated with hp lotion had a significantly greater reduction from baseline in affected bsa at week 8 versus vehicle, with significant differences observed as early as week 2 for females and week 4 for males; significant differences were sustained posttreatment for both females and males (figure 3) fran cook-bolden, md1; jennifer soung, md2; scott t guenthner, md3; brock bumpass, pharmd4; tina lin, pharmd4 1department of dermatology, mount sinai hospital center, new york, ny; 2southern california dermatology, santa ana, ca; 3the indiana clinical trials center, pc, plainfield, in; 4ortho dermatologics*, bridgewater, nj *ortho dermatologics is a division of bausch health us, llc. lilly immunology study was sponsored by eli lilly and company, under license from incyte corporationwinter clinical dermatology conference; hawaii, usa; january 13-18, 2023 methods study design, brave-aa1 and brave-aa2 disclosures ■ b. m. piraccini has been an investigator for, received honoraria and/or consulting fees from, and/or been a speaker for: concert pharmaceuticals, eli lilly and company, isdin, and pfizer; m. ohyama has received advisory and/or lecture fees from: eli lilly japan k.k., janssen, pfizer japan, rohto pharmaceutical, and taisho pharmaceutical; and has received research grants from: maruho, shiseido, and sun pharma japan; b. craiglow has received honoraria and/or fees from: eli lilly and company, pfizer, regeneron, and sanofi genzyme; a. bewley has received honoraria and/or consulting fees from: abbvie, almirall, eli lilly and company, galderma, janssen, leo pharma, novartis, sanofi, and ucb pharma; y. ding, y.-f. chen, y. dutronc, e. pierce, and f. durand are employees and stockholders of: eli lilly and company; a. mostaghimi has been a consultant for: abbvie, concert pharmaceuticals, digital diagnostics, eli lilly and company, and pfizer ■ medical writing assistance was provided by linda donnini, phd, of proscribe – envision pharma group, and was funded by eli lilly and company ■ this study is previously presented at european academy of dermatology and venereology 31st congress, 2022 scalp hair regrowth is associated with improvements in health-related quality of life and psychological symptoms in patients with severe alopecia areata: results from two randomized controlled trials bianca maria piraccini,1 manabu ohyama,2 brittany craiglow,3 anthony bewley,4 yuxin ding,5 yun-fei chen,5 yves dutronc,5 evangeline pierce,5 frederick durand,5 arash mostaghimi6 1university of bologna, bologna, italy; 2kyorin university faculty of medicine, tokyo, japan; 3yale school of medicine, new haven, usa; 4the royal london hospital, london, uk; 5eli lilly and company, indianapolis, usa; 6brigham and women’s hospital, harvard medical school, boston, usa background ■ alopecia areata (aa) is a common autoimmune disorder that results in hair loss1 – hair loss can range in severity, from loss of hair in small localized patches on the scalp, to complete loss of hair on the scalp (alopecia totalis) and/or body (alopecia universalis)1 ■ severe aa is frequently associated with health-related quality of life (hrqol) impairment and psychological burden2 ■ however, the impact of hair regrowth on hrqol and psychosocial burden has not been sufficiently investigated objective ■ to evaluate the association between scalp hair regrowth and improvement of hrqol and psychological burden in patients with severe aa using pooled data from the phase 3, randomized, placebo-controlled trials, brave-aa1 (nct03570749) and brave-aa2 (nct03899259) conclusions ■ patients with severe aa who achieved scalp hair regrowth at week 36 experienced improvements in hrqol and symptoms of anxiety and depression when compared with those who had no or minimal regrowth – higher benefit was observed in patients achieving a salt ≤20 response – improvements were also observed in the intermediate response group, but generally to a lesser extent than those in the salt ≤20 response group ■ these results support the clinical relevance of salt ≤20, the primary endpoint for the baricitinib clinical program in severe aa ■ longer treatment duration may be needed to assess the full impact on scalp hair regrowth, hrqol, and symptoms of anxiety and depression abbreviations aa=alopecia areata; b/ab=borderline/abnormal; bari=baricitinib; hads-a=hospital anxiety and depression scale– anxiety; hads-d=hospital anxiety and depression scale–depression; hrqol=health-related quality of life; lsm=least squares mean; mlocf=modified last observation carried forward; nri=non-responder imputation; pbo=placebo; qd=once daily; salt=severity of alopecia tool; w=week key results scan or click the qr code or use this url (https://lillyscience.lilly.com/congress/wcdc2023) for a list of all lilly content presented at the congress. other company and product names are trademarks of their respective owners. references 1. pratt c, et al. nat rev dis primers. 2017;3:17011 2. mostaghimi a, et al. dermatol ther (heidelb). 2021;11:867-883. 3. olsen ea, et al. j am acad dermatol. 2004;51:440-447. results patient subgroups note: figure is not the full study design, but only the pbo-controlled period of both trials key eligibility criteria for brave-aa1 and brave-aa2 inclusion ■ age ≥18 years to ≤60 years (males) or ≤70 years (females) ■ severe or very severe aa – hair loss encompassing ≥50% of the scalp, as measured by the severity of alopecia tool (salt) ■ current episode of aa lasting >6 months to <8 yearsa exclusion ■ no spontaneous improvement in the 6 months before screening ■ not primarily a “diffuse” type of aa ■ no concomitant treatments for aa allowedb a patients who had aa for ≥8 years could be enrolled if episodes of regrowth (spontaneous or due to under-treatment) had been observed on the affected areas over the past 8 years b oral/topical minoxidil or finasteride were allowed if on stable dose for 12 months and bimatoprost ophthalmic solution was allowed if on stable dose for 8 weeks salt score3 ■ assesses hair loss in each quadrant of the scalp ■ the salt score is a weighted sum of the percent of hair loss in the 4 quadrants of the scalp, ranging from 0 to 100 ■ examples: – salt 0=no scalp hair loss​ – salt 50=50% scalp hair loss​ – salt 100=complete scalp hair loss ■ patients were categorized into 3 groups according to scalp hair regrowth at week 36: 1. salt ≤20 response (n=256): met the primary endpoint of salt ≤20 (ie, ≥80% scalp hair coverage) 2. intermediate response (n=268): did not meet the primary endpoint but achieved ≥30% improvement from baseline in salt score at any postbaseline visit up to week 36 (salt30) 3. no or minimal response (n=676): did not achieve salt30 at any post-baseline visit up to week 36 assessments skindex-16 adapted for aa: assessed effects of aa on hrqol over 3 domains: ■ emotions, symptoms, and functioning ■ each domain score ranged from 0 to 100, with higher scores indicating worse hrqol hospital anxiety and depression scale (hads): assessed levels of anxiety (hads-a) and depression (hads-d)a ■ each domain score ranged from 0 to 21, with higher scores indicating greater anxiety or depression ■ used to identify patients with borderline or abnormal severity scores at baseline (hads-a ≥8 or hads-d ≥8) a patients with significant uncontrolled neuropsychiatric disorder were not eligible for the study statistical analyses ■ data were pooled from the 3 arms (placebo, baricitinib 4-mg, and baricitinib 2-mg) of brave-aa1 and brave-aa2 and analyzed independently of treatment allocation ■ change from baseline in skindex-16 domains, hads-a, and hads-d scores were analyzed using analysis of covariance with modified last observation carried forward imputation for missing data – data after permanent study drug discontinuation were censored and not carried forward ■ percentage of patients who shifted from borderline or abnormal to normal hads-a and hads-d scores were analyzed using logistic regression with nonresponder imputation demographics and baseline characteristics, by hair regrowth response group response categories according to scalp hair regrowth at week 36 for pooled treatment arms salt ≤20 response (n=256) intermediate response (n=268) no or minimal response (n=676) age, years 37.4 (12.5) 37.3 (12.6) 37.7 (13.1) female, n (%) 166 (64.8) 149 (55.6) 413 (61.1) duration from onset of aa, years 9.0 (9.3) 11.5 (10.7) 13.6 (11.2) duration of current aa episode, years 3.0 (3.5) 3.5 (3.0) 4.4 (5.0) salt score 77.3 (18.9) 81.8 (18.3) 89.8 (16.1) salt category, n (%) severe (salt 50-94) 179 (69.9) 157 (58.6) 225 (33.3) very severe (salt 95-100) 77 (30.1) 111 (41.4) 450 (66.7) skindex-16 aa domain scorea symptoms 19.4 (20.2) 19.0 (20.9) 17.6 (19.9) emotions 70.3 (25.9) 68.3 (27.3) 67.0 (28.7) functioning 52.4 (30.9) 50.0 (32.6) 49.5 (32.2) patients with b/ab anxiety (hads-a ≥8), n (%) 94 (36.7) 96 (35.8) 220 (32.5) patients with b/ab depression (hads-d ≥8), n (%) 44 (17.2) 52 (19.4) 104 (15.4) hads-a scoreb 10.5 (2.7) 10.3 (2.3) 10.7 (2.8) hads-d scoreb 10.0 (1.9) 9.7 (2.0) 9.9 (2.0) * p<0.05; ** p<0.01; *** p<0.001 vs. no or minimal response patients with a salt ≤20 response at week 36 were more likely to achieve normal anxiety and depression scores (hads <8) * p<0.05; ** p<0.01 vs. no or minimal response in patients with borderline or abnormal severity scores at baseline (hads-a ≥8 or hads-d ≥8) greater improvement (decrease) in all skindex-16 aa domain scores was observed in patients with a salt ≤20 response at week 36 greater improvement (decrease) in anxiety and depression scores was observed in patients with a salt ≤20 response at week 36 * p<0.05; vs. no or minimal response in patients with borderline or abnormal severity scores at baseline (hads-a ≥8 or hads-d ≥8) data are mean (standard deviation) unless stated otherwise a in patients with baseline assessment of skindex-16 adapted for aa b in patients with baseline hads-a ≥8 or hads-d ≥8 poster presented at the 39th annual fall clinical dermatology conference; oct 17-20, 2019; las vegas, nv © dermira inc, 2019 limited systemic exposure with topical glycopyrronium tosylate across multiple studies in healthy volunteers and patients with primary axillary hyperhidrosis d. m. pariser1, e. l. lain2, r. mamelok3, j. drew4, d. r. mould5 1eastern virginia medical school and virginia clinical research, inc., norfolk, va; 2austin institute for clinical research, austin, tx; 3mamelok consulting, palo alto, ca; 4dermira, inc., menlo park, ca; 5projections research, inc., phoenixville, pa introduction • hyperhidrosis is a chronic medical condition characterized by excess sweat production beyond that which is necessary to maintain thermal homeostasis, and affects an estimated 4.8% of the united states (us) population, or approximately 15.3 million people1 • glycopyrronium tosylate (gt) is a topical anticholinergic approved in the us for treatment of primary axillary hyperhidrosis in patients ≥9 years of age (glycopyrronium cloth, 2.4%, for topical use)2 • pharmacokinetic (pk) and safety data were evaluated in an open-label, phase 1 study of topical gt and oral glycopyrrolate solution • population pk analyses were performed using data from two double-blind, phase 2 studies in patients with primary axillary hyperhidrosis across a range of glycopyrronium concentrations from the administration of gt or glycopyrronium bromide (hh01 [nct02016885], hh02 [nct02129660]) objectives • to compare the pk, safety, and tolerability of topical gt to orally dosed glycopyrrolate in an open-label, phase 1 study • to assess the relationship of the topical glycopyrronium pk profile to anticholinergic-related adverse events or efficacy using a population pk and pharmacodynamic model applied to data from two phase 2 studies methods study design open-label phase 1 study • gt 2.4% was applied by study staff (controlling for application method and preventing non-axillary exposure) once daily to both axillae of patients 9 to 65 years of age with primary axillary hyperhidrosis for 5 days (figure 1) – pediatric patients (9 to <18 years) participating in a gt open-label extension study (nct02553798), were allowed to participate concurrently in this study; these patients underwent a 7-day wash-out of gt prior to day 1 of this study – patients eligible for the gt arm of the trial had primary axillary hyperhidrosis for ≥6 months, gravimetrically measured sweat production of ≥50 mg/5 min in each axilla, axillary sweating daily diary (asdd) item 2 (severity) score ≥4 (0 to 10 numeric rating scale), and hyperhidrosis disease severity scale (hdss) grade 3 or 4 • oral glycopyrrolate solution was administered to healthy adult volunteers 18 to 65 years of age every 8 hours for 15 days, starting at 1.0 mg and titrated in 1.0 mg increments every 5 days (max 3.0 mg/8 hr), provided there were no dose limiting side effects (figure 1) • blood samples were collected on days 1-5 in patients treated with gt and days 1, 5, 10, and 15 in those administered with oral glycopyrrolate – gt-treated subjects underwent intensive pk sampling on days 1 and 5 and a pre-dose pk sample on days 3, 4, and 5; pediatric subjects (9 to <18 years of age) had a modified pk sampling schedule to comply with guidelines regarding safe volumes of blood sampling; no samples were collected in pediatric subjects on days 2, 3, and 4 – oral glycopyrrolate-treated subjects underwent intensive pk sampling on days 1, 5, 10, and 15 – noncompartmental pk analysis was conducted using winnonlin (version 6.3, pharsight corp., mountain view, ca) • adverse events (aes) were recorded throughout the study • a safety follow-up telephone call was conducted on day 7, or 2 days after the subject early-terminated in patients treated with gt, and on day 17, or 2 days after the subject stopped dosing in subjects treated with oral glycopyrrolate • the pk evaluable population included subjects who received study drug and had ≥1 pk sample collected • concentration values excluded from analysis were any pk samples with – detectable concentrations of glycopyrronium in pre-dose samples on day 1, and – plasma concentration values ≥3 standard deviations from the mean value for a given time point double-blind phase 2 studies (hh01, hh02) • in hh01, adult patients (>18 years of age) with primary axillary hyperhidrosis were randomized 1:1:1:1:1 to one of 4 doses of topical glycopyrronium bromide (0.8%, 1.6%, 2.4%, 3.2%) or vehicle (figure 2) • in hh02, adult patients (>18 years of age) with primary axillary hyperhidrosis were randomized 1:1:1:1:1 to one of 2 doses of gt (1.6%, 2.4%), one of 2 doses of glycopyrronium bromide (1.6%, 2.4%), or vehicle (figure 2) – under physiologic conditions, glycopyrronium bromide and gt dissociate, generating the glycopyrronium cation; therefore, the pharmacological activity is mediated by the active moiety, glycopyrronium; glycopyrronium has equivalent binding affinity for the m3 muscarinic acetylcholine receptor in vitro when delivered as either the bromide or the tosylate salt3 • patients were to apply study drug to both axillae once daily for 4 weeks with a 2-week off-drug follow-up • pk data were collected from a subgroup in each study, and aes and efficacy data were recorded • in both studies, intensive blood sampling occurred on days 1-2 and, for one study also on days 15-16; additional sampling occurred in subsequent weeks • pk data from these phase 2 studies informed a population pk model (nonmem version 7.2.0 icon plc, dublin, ireland) from which exposure metrics were used to assess the relationship between topical glycopyrronium pk and anticholinergic-related aes or efficacy figure 1. phase 1 open-label study design 1study days 2 3 4 5 6 study exit 7 safety follow-upa 1study days 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 study exit 17 safety follow-upa cohort 1 (n = ~25) cohort 2 (n = ~18) topical glycopyrronium tosylate in pahh patients (age 9-65 years) oral glycopyrrolate solution in healthy adult volunteers (age 18-65 years) once daily topical glycopyrronium tosylate treatment, applied to both axillae oral glycopyrronium solution doseb intensive pk sampling pre-dose pk sample pediatric patients (included in cohort 1 only; age 9 to <18 years) had a modified pk sampling schedule to comply with guidelines for safe volumes of blood sampling; no pre-dose samples were collected in pediatric subjects on days 2, 3, and 4 ain case of early termination, safety follow-up occurred 2 days after early termination bdose started at 1.0 mg every 8 hours on day 1 and escalated in 1.0 mg increments every 5 days provided there were no dose limiting side effects, up to a maximum dose of 3.0 mg every 8 hours glycopyrronium tosylate was applied and oral glycopyrrolate was administered by study staff pahh, primary axillary hyperhidrosis; pk, pharmacokinetics figure 2. phase 2 double-blind study design study weeks 5 6 hh01 (n = ~200) glycopyrronium 0.8%, 1.6%, 2.4% or 3.2% (bromide) vehicle glycopyrronium 1.6% or 2.4% (tosylate) glycopyrronium 1.6% or 2.4% (bromide) vehicle 0 a 1 2 3 4 applied once-daily off-drug follow-up period study weeks 3 hh02 (n = ~100) 10 c b 2 e d 4 5 6 applied once-daily off-drug follow-up period pre-dose samples (0 h) post-dose samples (0.5, 1, 2, 3, 4, 24 h post-dose) post-dose samples (0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 h post-dose) an= 32 subjects; bn=79 subjects; cn=10 subjects; dfor these subjects, a pk sample was drawn prior to the first dose of study drug at the day 1 visit; en =14 subjects h, hours; pk, pharmacokinetics assessments open-label phase 1 study • pk was assessed through collection of blood samples at pre-specified time points for determination of plasma concentrations of glycopyrronium • the plasma concentrations of glycopyrronium measured in the subjects were used to calculate the following key pk parameters: maximum plasma concentration (cmax), area under the plasma concentration versus time curve from 0 to 24 hours (auc0-24), area under the plasma concentration versus time curve from 0 to 6 hours (auc0-6), and terminal elimination phase half-life (t1/2) • safety was assessed through aes, local skin reactions (gt-treated patients only), safety laboratory tests (serum chemistry, hematology, and urinalysis), vital signs, physical examinations, and electrocardiograms population pk analysis of double-blind phase 2 studies (hh01, hh02) • three databases were assembled – population pk database: all concentration data from the active treatment arms from hh01 and hh02 were pooled into a single nonmem database – population pk ae database: included information on glycopyrronium exposure and the most severe grade of aes that could be due to anticholinergic activity • three categories of aes were defined as 1. dry mouth alone 2. dry mouth, vision blurred, urinary retention, dry eye, mydriasis, urinary hesitation, urine flow decreased, dry tongue 3. all events in group 2 plus constipation, nasal dryness, vulvovaginal dryness • the worst reported grade was captured using a numerical code (0 for no events, 1 for mild, 2 for moderate and 3 for severe) for all patients (including those randomized to the vehicle arm) – population pk pd database: included information on glycopyrronium exposure and multiple assessments of gravimetric and hdss scores results open-label phase 1 study subject disposition and baseline characteristics • in the phase 1 study, 11 adult (mean age 26 years, 63.6% female) and 20 pediatric patients (mean age 14.8 years, 65.0% female) received topical gt, and 18 adults (mean age 44.0 years, 88.9% male) received oral glycopyrrolate (table 1) table 1. phase 1 open-label subject disposition and baseline characteristics characteristic topical glycopyrronium tosylate adults n=11 topical glycopyrronium tosylate pediatric (9 to <18 y) n=20 oral glycopyrrolate adults n=18 subjects enrolled/completed safety populationa pk evaluable populationb 11/11 11 11 20/20 20 20c 18/18 18 18 age mean (sd) min, max 26.0 (8.92) 18, 49 14.8 (1.64) 10, 17 44.0 (10.35) 18, 58 gender, n (%) male female 4 (36.4) 7 (63.6) 7 (35.0) 13 (65.0) 16 (88.9) 2 (11.1) race, n (%) white black or african american other 9 (81.8) 2 (18.2) 0 13 (65.0) 7 (35.0) 0 9 (50.0) 8 (44.4) 1 (5.6) ethnicity, n (%) hispanic or latino not hispanic or latino 2 (18.2) 9 (81.8) 0 20 (100.0) 2 (11.1) 16 (88.9) weight (kg), mean (sd) 87.8 (27.7) 67.2 (16.9) 80.2 (9.8) bmi (kg/m2), mean (sd) 29.4 (6.3) 23.9 (5.6) 27.2 (2.4) asubjects who were enrolled and received ≥1 confirmed dose of study drug; bsubjects who received study drug and had ≥1 pk sample collected; c19 and 20 subjects, respectively, were included in pk evaluable population for day 1 and day 5 bmi, body mass index; pk, pharmacokinetics; sd, standard deviation pk findings • in adults treated with gt, pk parameters (mean ± sd) were cmax 0.08 ± 0.04 ng/ml, auc0-6h 0.20 ± 0.14 h*ng/ml, and auc0-24 0.88 ± 0.57 h*ng/ml (table 2); similar results were observed for pediatric patients (table 3) • for adults receiving oral glycopyrrolate 1, 2, and 3 mg, respectively, mean ± sd pk parameters were cmax 0.15 ± 0.12, 0.23 ± 0.11, and 0.38 ± 0.19 ng/ml, and auc0-24 2.12 ± 1.47, 3.50 ± 1.50, and 5.50 ± 2.19 h*ng/ml ± sd (table 2) table 2. pk findings for oral glycopyrrolate vs. topical glycopyrronium tosylate oral vs topical adults cmax mean ± sd ng/ml auc0-24 mean ± sd ng h/ml t1/2 h oral glycopyrrolatea 1 mg/q 8 h (n=18, day 5/15) 2 mg/q 8 h (n=18, day 10/15) 3 mg/q 8 h (n=18, day 15/15) 0.154 ± 0.118 0.227 ± 0.106 0.381 ± 0.190 2.12 ± 1.47 3.50 ± 1.5 5.50 ± 2.19 2.59 ± 0.649b 2.8 ± 0.481c 2.76 ± 0.879d topical glycopyrronium tosylatea (n=11, day 5/5) 0.08 ± 0.04 0.88 ± 0.57 could not be determinede afasting; bn=14; cn=11; dn=12; ea clear terminal elimination phase was not evident following topical glycopyrronium tosylate administration due to a lack of concentrations above the lower limit of quantitation; thus, no half-life could be reported in adult and pediatric patients auc, area under the plasma concentration over time curve; cmax, maximum plasma concentration; h, hours; pk, pharmacokinetics; sd, standard deviation; t1/2, elimination (terminal) half life table 3. pk findings for topical glycopyrronium tosylate in adult vs. pediatric patients adult vs pediatric (topical) cmax mean ± sd ng/ml auc0-24 mean ± sd ng h/ml tmax median (range) h adult patients 0.08 ± 0.04 (n=11) 0.88 ± 0.57 (n=7) 1 (0,10) (n=11) pediatric patients 0.07 ± 0.06 (n=20) not calculateda 1.5 (0,6) (n=19) apediatric samples were only collected up to 6 hours post-dose per guidelines on safe blood sampling therefore auc0-24 could only be determined for adults auc, area under the plasma concentration over time curve; cmax, maximum plasma concentration; pk, pharmacokinetics; sd, standard deviation; tmax, time to maximum plasma concentration safety • no anticholinergic-related treatment-emergent adverse events (teaes) occurred with gt, while those occurring with oral glycopyrrolate included dry mouth (16.7%) and nasal dryness (5.6%) (table 4) • no treatment related teaes were reported with gt (table 4) table 4. safety findings (topical glycopyrronium tosylate versus oral glycopyrrolate) n (%) topical glycopyrronium tosylate n=31 oral glycopyrrolate n=18 adult n=11 pediatric n=20 total n=31 teaes dry moutha headache nocturia chest pain hypoaesthesia nasal drynessa cough laceration rhinorrhea 2 (18.2) 0 2 (18.2) 0 0 0 0 0 0 0 3 (15.0) 0 2 (10.0) 0 0 0 0 1 (5.0) 1 (5.0) 1 (5.0) 5 (16.1) 0 4 (12.9) 0 0 0 0 1 ( 3.2) 1 ( 3.2) 1 ( 3.2) 7 (38.9) 3 (16.7) 1 ( 5.6) 2 (11.1) 1 ( 5.6) 1 ( 5.6) 1 ( 5.6) 0 0 0 teae by severity mild moderate severe 2 (18.2) 0 0 3 (15.0) 0 0 5 (16.1) 0 0 7 (38.9) 0 0 treatment-related teae 0 0 0 5 (27.8) serious teaes 0 0 0 0 teae leading to discontinuation 0 0 0 0 ateaes ascribed to anticholinergic effects occurred only with oral glycopyrrolate solution teae, treatment-emergent adverse event double-blind phase 2 studies (hh01, hh02) subject demographics and baseline characteristics • in the population pk analysis, 985 pk samples from 108 patients (mean age 32.6 years, 55.6% male) and ae/efficacy data for 137 patients (n=108 glycopyrronium, n=29 vehicle; mean age 32.8 years, 53.3% male) were included (table 5) • because of the large number of subjects from both studies that had no measurable glycopyrronium concentrations, a mixture of models approach was used where patients were classified as “absorbers” (eg, those that had measurable glycopyrronium concentrations) and “non-absorbers” (eg, those who never had measurable glycopyrronium concentrations) – it is not known what factor(s) may lead to this difference in absorption (eg, drug application variability, skin thickness, etc) table 5. phase 2 double-blind subject demographics and baseline characteristics characteristic pk database n=108 pk ae & pd database n=137 demographics age mean (sd) min, max 32.6 (11.6) 18, 72 32.8 (11.2) 18, 72 gender, n (%) male female 60 (55.6) 48 (44.4) 73 (53.3) 64 (46.7) race, n (%) caucasian black asian other 94 (87.0) 10 (9.3) 1 (0.9) 3 (2.8) 121 (88.3) 12 (8.8) 1 (0.7) 3 (2.2) weight (kg), mean (sd) 84.1 (22.6) 83.4 (22.2) bmi (kg/m2), mean (sd) 28.4 (6.2) 28.0 (6.0) other characteristics formulation, n (%) glycopyrronium bromide glycopyrronium tosylate vehicle 66 (61.1) 42 (38.9) na 66 (48.2) 42 (30.6) 29 (21.2) statusa, n (%) absorber non-absorber 71 (65.7) 37 (34.3) na aabsorbers were those that had measurable glycopyrronium concentrations; non-absorbers were those who never had measurable glycopyrronium concentrations ae, adverse event; bmi, body mass index; na, not applicable; pd, pharmacodynamics; pk, pharmacokinetics; sd, standard deviation • bioavailability was low (<0.5%) • there was no evidence of accumulation with repeat dosing • systemic exposure did not predict efficacy • anticholinergic aes were associated with higher glycopyrronium concentrations; however, the median cmax value was low (0.026 µg/l [min, max (0, 1.67)]; figure 3) figure 3. probability of anticholinergic adverse events (frequency) cmax (µg/l) probability of event probability of no event median cmax (0.026 ug/l) 1.0 0.7 0.8 0.9 0.6 0.2 0.3 0.1 0.4 0.5 0 p ro ba bi lit y of a dv er se e ve nt s 0.0 0.5 1.0 1.5 shading denotes the 95% confidence interval; patients randomized to vehicle were assigned a value of “0” for glycopyrronium exposure cmax, maximum plasma concentration; max, maximum; min, minimum; pk, pharmacokinetics • a low probability of mild aes is expected at low peak concentrations (figure 4) • the probability of moderate/severe aes does not become appreciable (over 20%) until cmax values of approximately 0.2 ug/l; however, most patients did not reach this level (figure 4) • most patients (83%) had a relatively low glycopyrronium cmax (gray box on the left; figure 4) • 6.5% of patients had a higher glycopyrronium cmax (gray box on the right, figure 4) • for comparison, pooled aes of two 4-week, phase 3, double blind studies of gt showed that mild aes were experienced by 22.8% of vehicle patients and 37.0% gt-treated patients; moderate aes were experienced by 9.5% of vehicle patients and 18.1% of gt patients, and severe aes were experienced in 0% of vehicle patients, and 0.9% of gt patients; adverse events infrequently led to discontinuation in those phase 3 studies (<4%)4 figure 4. probability of anticholinergic adverse events (severity) cmax (µg/l) 1.0 0.7 0.8 0.9 0.6 0.2 0.3 0.1 0.4 0.5 0 p ro ba bi lit y of a dv er se e ve nt s 0.0 0.5 1.0 1.5 83% of patients in this cmax range 6.5% of patients in this cmax range probability of moderate or severe event probability of mild event probability of no event shading denotes the 95% confidence interval ae, adverse event; cmax, maximum plasma concentration conclusions • in the phase 1 study, systemic absorption of glycopyrronium was lower in those treated with gt compared with oral glycopyrrolate, consistent with the lack of anticholinergic aes observed with gt in this study • exposure-response models suggest that the probability of aes increases in frequency and severity with increasing glycopyrronium cmax, while efficacy may be mediated locally versus systemically • pk parameters of gt indicate limited systemic absorption and a low risk of aes with proper administration – consistent with these pk modeling results from phase 2 data, most teaes in the phase 3 double-blind trials were mild references 1. doolittle et al. arch dermatol res. 2016;308(10):743-9. 2. qbrexzatm (glycopyrronium) cloth [prescribing information]. dermira, inc., menlo park, ca. 2018. 3. glycopyrronium muscarinic m3 receptor binding, life technologies corporation, 13-24. 4. glaser et al. j am acad dermatol. 2019 jan;80(1):128-138.e2. acknowledgements this study was funded by dermira, inc. medical writing support was provided by prescott medical communications group (chicago, il). all costs associated with development of this poster were funded by dermira, inc. author disclosures dmp: paid consultant and investigator for dermira, inc. ell, rm, drm: paid consultant for dermira, inc. jd: employee of dermira, inc. skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 139 brief articles successful treatment of pityriasis rubra pilaris with brodalumab umair khan1, nahla shihab md2, robert g. phelps md3, mark lebwohl md4 1medical student, eastern virginia medical school, norvolk, va 2clinical dermatology fellow, department of dermatology, icahn school of medicine at mount sinai, new york, ny 3professor and director, department of dermatopathology, icahn school of medicine at mount sinai, new york, ny 4professor and chairman, department of dermatology, icahn school of medicine at mount sinai, new york, ny pityriasis rubra pilaris (prp) is a rare papulosquamous inflammatory dermatosis of unknown etiology that may affect skin, nails, and hair. prp is extremely rare with an estimated incidence of 1/5000 and often mistaken for erythrodermic psoriasis1. the condition mostly affects adults in their sixth or seventh decade of life with no predilection for genders and is subdivided into six different subtypes based on clinical features, age of onset and prognosis.2,3 we present the case of a patient with type i (classic adult onset) prp who achieved complete resolution after initiation with combination therapy of brodalumab and methotrexate. a 62-year-old gentleman with a family history of psoriasis presents with a twenty year history of intermittent redness and dryness of the hands, scalp, and groin that receded with over the counter medications. in the past two years, he noticed that the patches became persistent and progressively worse. the patient was diagnosed with plaque psoriasis by his previous dermatologist and failed to improve with the use of topical steroids, a topical calcineurin inhibitor, and topical vitamin d3 analogue. despite a year on these topical treatments, the rash continued to spread predominantly to his face, trunk, and extremities, and his dermatologist decided to start systemic medications. the first combination consisted of cyclosporine and ustekinumab for three months with no visible improvement. the biologic was then changed to ixekizumab for another three months displaying only minor improvement. finally, the dose of cyclosporine was increased from 350mg to 400mg and the patient started on guselkumab, which lead to noticeable improvement. on week nine of this regimen, cyclosporine was stopped introduction case report pityriasis rubra pilaris (prp) is a rare inflammatory skin disease with highly variable clinical appearance. treatment of prp remains a challenge and has been mostly guided by case reports and case series. we report the first case of pityrisis rubra pilaris that is successfully treated with combination therapy of brodalumab and methotrexate. abstract skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 140 when the patient developed liver toxicity that was attributed to the cyclosporine; within days of cessation, the patient developed a severe and rapid exacerbation of the skin and new onset scalp hair loss. the patient then presented to our clinic with generalized erythematous-orange scaly patches with islands of sparing (figure 1a). based on his clinical presentation we diagnosed him as classic adult onset pityriasis rubra pilaris (prp). a skin biopsy was obtained from his right upper arm. the epidermis was acanthotic with mild spongiosis. there were foci of parakeratosis accentuated around hair follicles. the parakeratosis showed both a horizontal and vertical alternating pattern. foci of acantholysis were present. the features were consistent with pityriasis rubra pilaris with secondary spongiotic change (figure 2). we decided to start him on brodalumab 210mg every two weeks and on week six of treatment, we also added methotrexate 25mg every week. by week twelve of initiating brodalumab (figure 1b), the patient displayed significant clinical improvement. long-term remission continued through six months of combination therapy of brodalumab and methotrexate with no adverse events. figure 1a. patient at his initial presentation to our clinic. figure 1b. patient at 12 weeks of brodalumab treatment. skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 141 figure 2. acanthothic, mild spongiosis, with foci of parakeratosis horizontal and vertical alternating pattern pityriasis rubra pilaris and plaque psoriasis are two distinct erythemato-squamous skin diseases that are often challenging to differentiate. ross et al. did a multinational study of 100 patients that showed only 26% of patients were correctly diagnosed as having prp at the time of enrollment, with the most common initial diagnoses reported as being either psoriasis or eczema.4 on average, this delayed the correct diagnosis by 29 months from initial presentation4. clinically, patients with classic adult-onset prp typically present with a fine orange-red scaling eruption that is associated with erythroderma, palmoplantar keratoderma and a cephalocaudal progression of coalescing plaques with islands of sparing. complete remission is achieved spontaneously within three years of onset in 80% of cases, whereas recurrence occurs in 20% of cases.2 in comparison, plaque psoriasis presents with diffuse coarse silvery scales attached to an erythematous base. prp can also present with additional cutaneous features such as nails that are thickened, discolored, and ridged, whereas psoriasis patients display nail changes such as nail pitting, the oil drop sign, and distal onycholysis. the scalp involvement in both psoriasis and prp may include dandruff and scaly scalp, as well as hair shedding; the atypical form of prp is more often associated with alopecia and lesions localized to the lower extremities.5-7 on histopathology, type i prp demonstrates orthokeratosis with spotty parakeratosis, epidermal acanthosis, intact granular layer, and mild perivascular lymphohistiocytic infiltrates in the dermis. in psoriasis, the granular layer is often absent or very thin4. thus, the time-course, clinical presentation, and histopathology are crucial for distinguishing prp from plaque psoriasis. we present the first case of a patient with classic adult onset prp who failed several biologics and immunosuppressants but was able to achieve complete resolution with combination therapy of brodalumab and methotrexate. brodalumab is a human monoclonal antibody against the interleukin17 receptor a (il-17a) approved in 2017 by the food and drug administration for the treatment of moderate to severe plaque psoriasis. feldmeyer et al. reported a case of biopsy proven prp and found upregulated expression of proinflammatory cytokines including t17 helper cells (th17) cytokines il-17a, il-17f, and il-22 and tumor necrosis factor (tnf), il-6, il-12, il23, il-1β.8 analysis of the prp patient’s skin sample after treatment with ustekinumab discussion skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 142 showed decreased levels of th17 cytokines with clinical and histopathologic improvement of the disease.8 methotrexate is a second line monotherapy for prp that disrupts folate metabolism and downstream synthesis of thymidine. in a selection of published cases, type i prp patients displayed a 50% treatment response rate to methotrexate alone9. although no studies exist on the efficacy of brodalumab and methotrexate, prp data from select published cases demonstrate biologics offer a similar or higher response rate in comparison to isotretinoin and immunosuppressants.10-12 the excellent response of this patient to combination of brodalumab and methotrexate, introduces an additional biologic in the potential treatment options for pityriasis rubra pilaris. treatment options for pityriasis rubra pilaris (prp) are limited and often unsatisfactory. brodalumab in combination with methotrexate might be a promising therapeutic agent for patient with prp. conflict of interest disclosures: none funding: none corresponding author: nahla shihab md department of dermatology icahn school of medicine at mount sinai 5 e 98th street, new york, ny 10029 phone: 212-241-9728 fax: 212-987-1197 email: nahla.shihab@gmail.com references: 1. wang, d., chong, v.cl., chong, ws. et al. am j clin dermatol (2018) 19: 377. https://doi.org/10.1007/s40257-017-0338-1 2. roenneberg, s, biedermann, t. pityriasis rubra pilaris: algorithms for diagnosis and treatment. j eur acad dermatol venereol 2018; 32( 6): 889– 898. 3. griffiths, w. (1980), pityriasis rubra pilaris*. clinical and experimental dermatology, 5: 105112. doi:10.1111/j.1365-2230.1980.tb01676.x 4. ross na, chung h, li q, andrews jk, keller ms, vitto j. epidemiologic, clinicopathologic diagnostic and management challenges of pityriasis rubra pilaris: a case series of 103 patients. jama dermatol. 2016;152(6):670-675 5. wain t, choy b, satchell ac, woods ja, frew jw. secukinumab in pityriasis rubra pilaris: a case series demonstrating variable response and the need for minimal clinical datasets. jaad case rep. 2018;4(5):500–505. published 2018 may 7. doi:10.1016/j.jdcr.2018.02.007 6. albert, m. r. and mackool, b. t. (1999), pityriasis rubra pilaris. international journal of dermatology, 38: 1-11. doi:10.1046/j.13654362.1999.00513 7. klein a, landthaler m, karrer s. pityriasis rubra pilaris. american journal of clinical dermatology. 2010;11(3):157–170. doi:10.2165/11530070 8. feldmeyer l, mylonas a, demaria o, et al. interleukin 23-helper t cell 17 axis as a treatment target for pityriasis rubra pilaris. jama dermatol. 2017;153(4):304-308. 9. barth, d. , harth, w. , treudler, r. and simon, j. c. (2009), successful treatment of pityriasis rubra pilaris (type 1) under combination of infliximab and methotrexate. jddg: journal der deutschen dermatologischen gesellschaft, 7: 1071-1073. doi:10.1111/j.16100387.2009.07154.x 10. wasilewska a, winiarska m, olszewska m, rudnicka l. interleukin-17 inhibitors. a new era in treatment of psoriasis and other skin diseases. postepy dermatol alergol. 2016;33(4):247–252. doi:10.5114/ada.2016.61599 11. napolitano m, abeni d, didona b. biologics for pityriasis rubra pilaris treatment: a review of the literature. journal of the american academy of dermatology. 2018;79(2):353359.e11. doi:10.1016/j.jaad.2018.03.036 12. moretta g, de luca ev, di stefani a. management of refractory pityriasis rubra pilaris: challenges and solutions. clin cosmet investig dermatol. 2017;10:451–457. published 2017 nov 9. doi:10.2147/ccid.s124351 conclusion https://doi.org/10.1007/s40257-017-0338-1 slide 1  the full analysis set (fas) included 200 subjects. of these, 53 subjects were in the dfd-29 (40 mg) group, 47 in dfd29 (20 mg), 48 in doxycycline (40 mg) and 52 in the placebo group. at week 16 the median reduction in total rosaqol was 11 points in dfd-29 (40 mg), 8 points in dfd-29 (20 mg), 3 points in doxycycline (40 mg) and 1 point in the placebo group (fig.1).  highly statistically significant treatment differences (p<0.0001) were demonstrated for dfd-29 (40 mg) versus placebo and doxycycline (40 mg), as well as for dfd-29 (20 mg) versus placebo.  the ofm study demonstrated that dfd-29 (40 mg) and oral doxycycline 40 mg, provide similar dermal interstitial space fluid (disf) levels of minocycline and doxycycline, respectively. dfd-29, a low dose oral minocycline, shows significant improvement in quality of life in subjects with papulopustular rosacea linda stein gold, md1; joshua zeichner, md2 ; shanavas alikunju, phd3; anirudh gautam, mpharm4; srinivas shenoy md5; preeti singh, md5; srinivas sidgiddi, md5 1henry ford medical center, detroit, mi; 2mount sinai hospital, ny; 3dr reddy’s laboratories ltd., hyderabad, india; 4dr reddy’s laboratories sa, basel, switzerland; 5dr reddy’s laboratories inc., princeton, nj introduction  rosacea is a chronic facial skin disease that can have an adverse effect on quality of life.  dfd-29 a low dose oral minocycline is being evaluated as an anti-inflammatory treatment option for papulopustular rosacea. conclusions  improvement in the quality of life is a significant unmet need in rosacea. dfd-29 has the potential to meet this unmet need, and be an important therapeutic tool in the physician’s armamentarium. methods figure 1. rosaqol reduction at week 16  this phase 2, randomized, double-blind trial enrolled adults with mild, moderate or severe papulopustular rosacea.  subjects were randomized to receive dfd-29 (minocycline hcl) 40 mg extended release (er) capsules, dfd-29, 20 mg er capsules, oraycea® (doxycycline hcl) 40 mg capsules or placebo, one capsule a day for 16 weeks.  a key endpoint in the study was to assess change in the quality of life (qol) using rosaqol (a rosacea specific qol tool) from baseline to week 16. rosaqol has 21 general questions each rated on a 5-grade scale, and 6 global questions. a reduction in the total rosaqol score indicates an improved qol.  in an earlier phase 1 study, the dermal interstitial space fluid (disf) levels of doxycycline (oraycea) and minocycline (dfd-29) were measured, using open-flow microperfusion (ofm) in healthy human subjects. financial support: this study was funded and sponsored by the dr. reddy’s laboratories group of companies, princeton, nj, 08540, usa. drl publication # 884 results -15 -10 -5 0 dfd-29 40mg, n=53 dfd-29 20mg, n=47 doxycycline 40mg, n=48 placebo, n=52 -11 m e d ia n r e d u c ti o n i n r o s a q o l 8 3 * # * -1 *statistical significance reported vs placebo, # statistical significance reported vs doxycycline patient tolerability of tazarotene foam, 0.1%, and impact on patient compliance a multicenter, open-label, phase 1 study of the safety, tolerability, systemic exposure, pharmacodynamics, and treatment effect of calcipotriene foam, 0.005% in pediatric subjects (ages 2 to 11 years) with plaque psoriasis. adelaide a. hebert, mda; debbie glaab msn, cpnp-acb; rhonda schreiber msrnb , calcipotriene foam, 0.005%, was well tolerated with a low incidence of adverse events in the pediatric population. there were no quantifiable systemic concentrations of calcipotriene nor effect seen on calcium metabolism with repeated application. while this study was not designed as an efficacy study, the % of subjects who were isga responders was found to be consistent with the efficacy in the treatment of body and scalp in adults. overall, the results in this pediatric population are consistent with previously reported clinical findings for adolescents and adults indicating that calcipotriene foam, 0.005% is safe, well tolerated, and effective treatment option for pediatric psoriasis patients. conclusions • phase 1 multicenter, open-label, repeat-dose study with 36 subjects ages 2 to 11 years from 16 sites. • two cohorts: • maximum use cohort defined as isga score of 3 or higher at screening and at least 3% body surface index (bsa) with some scalp involvement. • general use cohort defined as isga score of 2 or 3 at screening with no bsa minimum • subjects or their caregivers applied a thin layer of study product twice a day to the treatment areas (excluding the face) for 8 weeks: • in the event that the lesions cleared prior to the end of the study, subjects or their primary caregivers were to continue to apply study product to treatment areas originally affected by psoriasis. • any new psoriatic lesions which appeared in treatment areas during the treatment period were also treated with the study product. • safety assessments (adverse event and serious adverse event query) occurred at all study visits. • treatment effect, urine calcium metabolism, and application site tolerability assessments were performed for all subjects at all in-clinic visits. • blood samples were taken from all subjects at screening for evaluation of pharmacodynamic (pd) assessments and 25-oh vitamin d levels at baseline, and an additional blood draw for pd parameters was taken at week 2 for the maximum-use cohort only. • the % of subjects who were isga responders was compared to the phase iii adult clinical trial results using bayesian analysis. methods resultssynopsis primary objective: • to evaluate the safety and tolerability of calcipotriene foam, 0.005%, in pediatric subjects, ages 2 to 11 years, with mild to moderate plaque psoriasis. secondary objectives: • to evaluate the pharmacodynamic effect on calcium metabolism of calcipotriene foam 0.005%, in pediatric subjects, ages 2 to 11 years, with mild to moderate plaque psoriasis. • to describe the plasma concentrations of calcipotriene following administration of calcipotriene foam, 0.005% in pediatric subjects, ages 2 to 11 years, with moderate plaque psoriasis. • to describe the treatment effect of calcipotriene foam, 0.005%, in pediatric subjects, ages 2 to 11 years, with mild to moderate plaque psoriasis. objectives • pd markers showed a general lack of change over time and there were no quantifiable systemic concentrations of calcipotriene observed. the average values of corrected calcium, magnesium and phosphorus were consistent over time. the ipth and alkaline phosphatase showed some variability across time, but no consistent trends and similar values at screening and day 15. the variability in these values could likely be attributed to small sample size, especially in the subgroups. there was no relationship seen between urinary calcium/creatinine ratio and %bsa treated or age. • no serious adverse events were reported. of the 29 adverse events that were reported; 7 were considered related to the treatment. these adverse events presented themselves as mostly topical in nature. local tolerability results remained 0 from baseline to study end in 22 subjects (61.11%). • no evidence of a drug effect was noted for body weight, height, or vital signs. • isga scores improved with treatment, but differences between treatments could not be assessed because of the small number of subjects receiving vehicle and the study was not designed to show efficacy. however, response rates (% of subjects with an isga score of 0 or 1 for body or scalp at week 8) were consistent with that observed in the double-blind, vehicle controlled phase iii studies in adults. pd marker visit calcipotriene (cal) vehicle n mean (sd) min max n mean (sd) min max corrected calcium (mmol/l) screening 21 9.3 (0.22) 8.8 9.7 2 9.4 (0.14) 9.3 9.5 day 1 3 9.1 (0.17) 9.0 9.3 2 9.1 (0.07) 9.0 9.1 day 13 16 7 9.2 (0.24) 8.9 9.6 2 9.4 (0.35) 9.1 9.6 day 56 59 3 9.3 (0.35) 9.0 9.7 2 9.4 (0.14) 9.3 9.5 ipth (pmol/l) screening 19 29.0 (10.54) 12.0 46.0 2 54.0 (53.74) 16.0 92.0 day 1 3 45.0 (23.00) 22.0 68.0 2 49.0 (26.87) 30.0 68.0 day 13 16 7 32.1 (23.58) 16.0 84.0 2 25.0 (9.90) 18.0 32.0 day 56 59 3 49.7 (49.10) 16.0 106.0 2 26.5 (0.71) 26.0 27.0 alkaline phosphatase (µ/l) screening 21 274.4 (69.43) 160.0 415.0 2 267.0 (69.30) 218.0 316.0 day 1 3 357.7 (121.18) 221.0 452.0 2 272.0 (77.78) 217.0 327.0 day 13 16 6 292.3 (99.83) 184.0 446.0 2 296.0 (106.07) 221.0 371.0 day 56 59 3 316.7 (110.59) 190.0 394.0 2 279.0 (28.28) 259.0 299.0 magnesium (mmol/l) screening 21 1.8 (0.10) 1.6 1.9 2 1.6 (0.00) 1.6 1.6 day 1 3 1.7 (0.21) 1.5 1.9 2 1.7 (0.21) 1.5 1.8 day 13 16 6 1.7 (0.15) 1.5 1.9 2 1.7 (0.14) 1.6 1.8 day 56 59 3 1.8 (0.15) 1.6 1.9 2 1.6 (0.00) 1.6 1.6 phosphorus (mmol/l) screening 21 5.0 (0.47) 3.5 5.8 2 4.6 (0.42) 4.3 4.9 day 1 3 5.1 (0.06) 5.0 5.1 2 4.3 (0.42) 4.0 4.6 day 13 16 6 4.8 (0.56) 4.1 5.6 2 4.4 (0.49) 4.0 4.7 day 56 59 3 5.3 (0.46) 5.0 5.8 2 4.8 (0.21) 4.6 4.9 calcium/creatinine (mg/g creat) screening 18 77.0 (43.57) 11.0 172.0 2 101.5 (64.35) 56.0 147.0 day 1 21 66.9 (76.84) 7.0 286.0 2 101.5 (64.35) 56.0 147.0 day 13 16 18 72.5 (56.57) 7.0 220.0 2 67.0 (29.70) 46.0 88.0 day 56 59 19 90.2 (80.83) 5.0 285.0 2 61.0 (36.77) 35.0 87.0 pd marker at screening, day 1, day 13-16 and day 56-59 a. ut health mcgovern medical school-houston, houston, tx; b. mayne pharma, greenville, nc. this study and analysis was sponsored by mayne pharma. all research funding was paid to ut health mcgovern medical schoolhouston, houston, tx. affiliations and disclaimers references teae type n (%) # of events overall 6 (16%) 7 application site pain 2 (6.3%) 2 contact dermatitis 2 (6.3%) 2 psoriasis 3 (9.4%) 3 relative change from day 1 to day 15 and day 22 for pd markers summary of treatment emergent adverse events* *no aes reported in vehicle control group pd marker treatment n geometric mean 95% ci 90% ci corrected calcium (mmol/l) cal 7 0.997 0.976 1.018 0.971 1.024 vehicle 2 0.994 0.898 1.101 0.810 1.220 ipth (pmol/l) cal 7 1.069 0.697 1.639 0.624 1.831 vehicle 2 0.626 0.015 25.445 0.000 1083.9 alkaline phosphatase (u/l) cal 6 0.955 0.872 1.045 0.851 1.071 vehicle 2 1.091 0.686 1.734 0.429 2.772 magnesium (mmol/l) cal 6 0.971 0.923 1.021 0.910 1.035 vehicle 2 1.061 0.731 1.538 0.502 2.242 phosphorus (mmol/l) cal 6 0.991 0.907 1.082 0.885 1.109 vehicle 2 0.945 0.857 1.041 0.777 1.148 body n (%) scalp n (%) calcipotriene foam, 0.005% 14 (45.16) 19 (61.29) vehicle foam 1 (33.3) 1 (33.3) % subjects with isga score 0 or 1 at week 8 demographics calcipotriene foam, 0.005% n=32 vehicle foam n=4 demographics calcipotriene foam, 0.005% n=32 vehicle foam n=4 age (yrs) mean (sd) median min, max 8.6 (2.06) 9 4,11 8.5 (2.65) 9 5,11 baseline bsa: (%) mean (sd) median min,max 12.2 (9.94) 7.8 0.5,36.5 16.5 (8.26) 19.1 5,23 race: n (%) caucasian african american asian native american/alaskan other 25 (78) 4 (13) 0 1 (3) 2 (6) 3 (75) 0 1 (25) 0 0 baseline isga body mean sd median min,max baseline isga scalp mean sd median min,max 2.5 (0.92) 3 0,4 1.9 (1.34) 2 0,4 3 (0) 3 3,3 2.8 (0.50) 3 2,3 gender: n (%) male female 15 (47) 17 (53.) 2 (50) 2 (50) height (cm) mean sd median min,max 136.2 (13.91) 137.2 104,159 129.2 (11.59) 124.2 122,147 ethnicity: n (%) hispanic/latino not hispanic/latino 13 (42) 18 (58) 1 (25) 3 (75) weight (kg) mean sd median min,max 42.1 (15.56) 41.6 17.8,77.1 36.2 (12.23) 35.3 22.7,51.3 1. national psoriasis foundation. (2019, july 31). about psoriasis. retrieved from psoriasis.org: www.psoriasis.org/parents/about-psoriasis. 2. silverberg, n. b. (2009). pediatric psoriasis: an update. therapeutics and clinical risk management, 5, 849-856. 3. kimball, a., gold, m., zib, b., davis, m., & clobetasol propionate emulsion formulation foam ph. (2008). clobetasol propionate emulsion formulation foam 0.05%: review of phase ii open-label and phase iii randomized controlled trials in steroid-responsive dermatoses in adults and adolescents. jaad, 59(3), 448-454. 4. shah, k. n. (2013). diagnosis and treatment of pediatric psoriasis: current and future. american journal of clinical dermatology, 14, 195. 5. wolverton, s. e. (2001). comprehensive dermatologic drug therapy (xlx ed.). philadelphia, pa: saunders. 6. feldman , s. r., mills, m., brundage, t., & eastman, w. j. (2013, march). a multicenter, randomized, double-blind study of the efficacy and safety of calcipotriene foam, 0.005%, vs vehicle foam in the treatment of plaque-type psoriasis of the scalp. jdd, 12(3), 300-306. 7. hebert, a., glaab, d., & schrieber, r. (2019). a phase 1 open label multicenter study to evaluate the safety, tolerability, pharmacodynamics, and pharmacokinetics of calcipotriene foam, 0.005% applied under maximum use conditions in adolescent subjects with plaque psoriasis. skin: the journal of cutaneous medicine, 3(2). response rates for pediatric and adults from previous studies according to the national psoriasis foundation approximately 150,000 new psoriasis patients are diagnosed in the united states each year.1 almost 20,000 (13%) of newly diagnosed patients are children under the age of 10 with most manifesting with plaque psoriasis (68.6%) with lesions localized to the scalp, post auricular region, elbows, and knees.2 although the relative frequency of plaque psoriasis differs between adults and children, the etiology is thought to be the same as evidenced by similar response rates to therapies.3,4 there are few therapeutic options for the pediatric population that have proven safety and efficacy and that have fda approval in the pediatric population. calcipotriene is a synthetic vitamin d3 derivative that has been used effectively for many years for the treatment of plaque-type psoriasis.5 the efficacy and safety of calcipotriene foam, 0.005%, was established in phase iii clinical trials for the treatment of adults and recently the fda adjusted the indication to include treatment in patients 12 years and older due to proven safety in a phase i study in adolescents.6,7 the data presented here highlight the results of an additional phase i clinical study in pediatric subjects aged 2 to 11 years. 101102042_cobi_pop_pk_l1a presented at the winter clinical dermatology conference; january 13-18, 2023; kohala coast, hawaii copies of this poster and supplemental information, which can be obtained through this qr code, are for your personal use only and may not be reproduced without permission from the authors. copyright © 2023. all rights reserved. background • abrocitinib is an oral, once-daily, janus kinase 1–selective inhibitor approved for the treatment of with moderate-to-severe ad1-3 • an integrated safety analysis was previously published for abrocitinib clinical trials that included 2856 patients with moderate-to-severe ad4 • additional safety data have accrued from further randomized controlled trials and an ongoing long-term extension study • the integrated safety analysis presented here includes data from the largest population and longest follow-up period reported to date objective • to evaluate the long-term safety profile of abrocitinib and provide relevant information for practitioners methods study design • data from patients who received ≥1 dose of abrocitinib 200 mg or 100 mg in the jade clinical trial program were pooled into 2 cohorts (figure 1) – in the consistent-dose cohort, patients received the same abrocitinib dose during the entire exposure time in parent phase 3 studies and/ or the long-term extension study jade extend (nct03422822); data cutoff april 16, 2021 • parent studies were jade mono-1 (nct03349060), jade mono-2 (nct03575871), jade teen (nct03796676), jade compare (nct03720470), jade dare (nct04345367), and jade regimen (nct03627767) ◦ for jade regimen (200 mg only), only patients from the open-label run-in phase who did not subsequently enter the randomized phase were included • patients may have received their first dose of abrocitinib in jade extend if they previously received placebo in the placebocontrolled parent studies and/or dupilumab in jade compare or jade dare • patients from the phase 2b study (nct02780167) who received abrocitinib 200 mg or 100 mg were also included – in the variable-dose cohort, patients received different doses of abrocitinib (200 mg and 100 mg) throughout exposure time in the parent study (jade regimen) and were enrolled in jade extend • patients who completed the open-label period of jade regimen (abrocitinib 200 mg only) and entered the randomized phase (abrocitinib 200 mg, abrocitinib 100 mg, or placebo) were included • some patients subsequently entered the jade regimen rescue phase (abrocitinib 200 mg) and/or jade extend (abrocitinib 200 mg or 100 mg) figure 1. analysis cohorts data cutoff: april 16, 2021time consistent-dose cohort variable-dose cohort jade dare jade regimen (open-label run-in) jade regimen (open-label rescuec) jade regimen (open-label run-inb) jade extenda jade extenda jade mono-1 jade mono-2 jade compare jade teen phase 2b parent studies phase 3 placebo controlled trials jade regimen (randomized) placebo abrocitinib 100 mg qd abrocitinib 200 mg qd jade extend easi, eczema area and severity index; iga, investigator’s global assessment; qd, once-daily. jade extend is ongoing. a includes patients who received their first dose of abrocitinib (100 mg or 200 mg) in jade extend after receiving placebo in a phase 3 placebo-controlled trial or dupilumab in jade compare or jade dare. b patients in the open-label run-in period who achieved response (iga score of 0 [clear] or 1 [almost clear] and ≥75% improvement from baseline on the easi) after 12 weeks of treatment with abrocitinib 200 mg were randomly allocated to treatment with abrocitinib 200 mg, abrocitinib 100 mg, or placebo. c patients who experienced a flare (≥50% loss of week 12 easi response and new iga score of ≥2) during the randomized period entered the open-label rescue period (abrocitinib 200 mg plus topical medicated treatment). statistical analysis • incidence rates (irs; number of unique patients with events per 100 patient-years [py]) of adverse events were calculated – for ir calculations, patient exposure was calculated up to the time of first event for patients with events – time to event was censored at the end of the risk period for patients who did not experience an event • a cox proportional hazard regression analysis evaluated risk factors for specific events of interest results patients • data from 3582 patients were analyzed, representing 4313.4 py – the consistent-dose cohort (n=2784) included 1721.3 py of exposure to abrocitinib 200 mg (n=1761) and 1284.4 py of exposure to abrocitinib 100 mg (n=1023) • duration of exposure was ≥48 weeks in 767 of 1761 patients (43.6%) and 684 of 1023 patients (66.9%) and ≥96 weeks in 317 of 1761 patients (18.0%) and 237 of 1023 patients (23.2%) in patients treated with abrocitinib 200 mg and 100 mg, respectively – in the variable-dose cohort (n=798), total abrocitinib exposure was 1307.7 py; cumulative abrocitinib exposure was ≥48 weeks in 687 of 798 patients (86.1%) and ≥96 weeks in 362 of 798 patients (45.4%) • in the consistent-dose and variable-dose cohorts, median age was 30.0 and 29.0 years, 490 patients (17.6%) and 145 patients (18.2%) were adolescents, and 143 patients (5.1%) and 30 patients (3.8%) were aged ≥65 years at screening, respectively (supplementary table s1, accessible via the qr code) safety events • irs for saes, aes leading to treatment discontinuation, deaths, and other specific adverse events of interest are reported in figure 2 for the consistent-dose cohort and in supplementary figure s1 for the variable-dose cohort – irs for saes were higher in patients aged ≥65 years versus younger patients in the consistent-dose cohort – serious infections were the most frequent saes reported in both the consistent-dose cohort and the variable-dose cohort – irs for teaes leading to discontinuation were higher with abrocitinib 200 mg than with abrocitinib 100 mg • 7 deaths were reported in the consistent-dose cohort, including 5 in the abrocitinib 200 mg group (coronavirus disease 2019 [covid-19], n=2; septic shock, n=1; cardiac failure, n=1; cardiorespiratory arrest, n=1) and 2 in the abrocitinib 100 mg group(sudden death, n=1; covid-19, n=1); 2 of the deaths described here were previously reported. there was also an additional death (>200 days after last dose of abrocitinib) that was previously reported which involved gastric adenocarcinoma4 – no deaths were reported in the variable-dose cohort infections • irs for infections are reported in figure 2 for the continuous-dose cohort and in supplementary figure s1 for the variable-dose cohort • herpes zoster, herpes simplex, and pneumonia were the most frequent serious infections – most (95%) adjudicated opportunistic herpes zoster infections were cutaneous; 2 (5%) were extracutaneous (1 serious disseminated varicella zoster virus infection, 1 serious herpes zoster meningitis) – a trend towards a dose-dependent relationship was observed with herpes zoster infections • no risk factors were identified for serious infections in a cox regression analysis • potential risk factors for treatment-emergent herpes zoster included abrocitinib dose, age ≥65 years, medical history of herpes zoster, absolute lymphocyte count <1000/mm3 prior to infection, and region (supplemental table s2) malignancies and cardiovascular events • irs for malignancies and cardiovascular events are reported in figure 2 for the continuous-dose cohort, and in supplementary figure s1 for the variable-dose cohort – irs were higher in patients aged ≥65 years compared with younger patients hematological events • irs for thrombocytopenia and lymphopenia are reported in figure 2 for the continuous-dose cohort and in supplementary figure s1 for the variable-dose cohort – irs for thrombocytopenia and lymphopenia events were higher in patients aged ≥65 years compared with younger patients safety of abrocitinib in 3582 patients with moderate-to-severe atopic dermatitis with over 900 patients exposed for almost 2 years eric l. simpson,1 jonathan i. silverberg,2 audrey nosbaum,3 kevin winthrop,1 emma guttman-yassky,4 karin m. hoffmeister,5 alexander egeberg,6 hernan valdez,7 haiyun fan,8 saleem a. farooqui,9 gary chan,10 justine alderfer,8 william romero,11 susan johnson12 1oregon health & science university, portland, or, usa; 2the george washington university school of medicine & health sciences, washington, dc, usa; 3hospices civils de lyon, centre hospitalier lyon-sud, pierre bénite, france; 4icahn school of medicine, mount sinai medical center, new york, ny, usa; 5translational glycomics center, versiti blood research institute, milwaukee, wi, usa; medical college of wisconsin, milwaukee, wi, usa; 6bispebjerg hospital, university of copenhagen, copenhagen, denmark; 7pfizer inc., new york, ny, usa; 8pfizer inc., collegeville, pa, usa; 9pfizer r & d uk ltd., sandwich, kent, united kingdom; 10pfizer inc., groton, ct, usa; 11pfizer ltd., tadworth, surrey, united kingdom; 12pfizer inc., raleigh-durham, nc, usa figure 2. irs (95% ci) for adverse events of special interest in the consistent-dose cohort 2 30 5 101 154 ir, number of patients with events per 100 py deaths teaes resulting in permanent discontinuation saes serious herpes zoster adjudicated opportunistic herpes zoster serious infections serious eczema herpeticum serious herpes simplex adjudicated turberculosis adjudicated mace adjudicated nmsc adjudicated malignancies (excluding nmsc) adjudicated non fatal vtea rhabdomyolysis lymphopenia thrombocytopenia (confirmed platelet count <75 × 103/mm3) retinal detachment abrocitinib 100 mg qd (n=1023) abrocitinib 200 mg qd (n=1761) ir (95% ci) 6.31 (5.01-7.84) 7.28 (6.07-8.67) 8.64 (7.12-10.38) 13.00 (11.37-14.79) 0.15 (0.02-0.55) 0.28 (0.09-0.65) 2.43 (1.66-3.44) 2.46 (1.79-3.31) 0.61 (0.26-1.20) 1.23 (0.77-1.87) 0.15 (0.02-0.55) 0.50 (0.23-0.95) 0.08 (0.00-0.42) 0.11 (0.01-0.40) 0.38 (0.12-0.88) 0.06 (0.00-0.31) 0.00 (0.00-0.28) 0.06 (0.00-0.31) 0.08 (0.00-0.42) 0.33 (0.12-0.73) 0.38 (0.12-0.89) 0.17 (0.03-0.49) 0.15 (0.02-0.55) 0.22 (0.06-0.57) 0.08 (0.00-0.42) 0.28 (0.09-0.65) 0.00 (0.00-0.28) 0.45 (0.19-0.88) 0.00 (0.00-0.28) 0.56 (0.27-1.02) 0.00 (0.00-0.28) 0.06 (0.00-0.31) 0.15 (0.02-0.55) 0.11 (0.01-0.40) ir, incidence rate; mace, major adverse cardiac events; nmsc, non-melanoma skin cancer; py, person-years; qd, once-daily; sae, serious adverse events; teae, treatment-emergent adverse event; vte, venous thromboembolism. a1 pulmonary embolism embolism event (not adjudicated) was included. conclusions • for patients requiring janus kinase inhibitors to control moderate-tosevere ad, these data further clarify the overall long-term safety profile of abrocitinib – in this largest and longest analysis of abrocitinib in patients with moderate-to-severe ad to date, the aes identified were generally consistent with previous safety analyses4,5 • patient selection and dose selection are important considerations for prescribers – risk of saes, herpes zoster infection, malignancies, cardiovascular events, lymphopenia, and thrombocytopenia increased in patients aged ≥65 years – increased risk of herpes zoster also appeared to be related to higher abrocitinib dose, medical history of herpes zoster, geographic region, and absolute lymphocyte count <1000/mm3 prior to infection • these data support the acceptable safety profile of abrocitinib in the treatment of moderate-to-severe ad in eligible patients references 1. cibinqo (abrocitinib). summary of product characteristics. european medicines agency; december 17, 2021. 2. cibinqo (abrocitinib) tablets. prescribing information. pfizer labs; january 2022. 3. cibinqo (abrocitinib), 100 mg film-coated tablets. summary of product characteristics. pfizer ltd.; september 10, 2021. 4. simpson el et al. am j clin dermatol. 2021;22:693-707. 5. cork mj et al. presented at: european academy of dermatology and venereology (eadv) congress; september 29-october 2, 2021; berlin, germany. acknowledgments editorial/writing support under the guidance of authors was provided by megan k. elder, phd, at apothecom (san francisco, ca), and was funded by pfizer inc., new york, ny, usa, in accordance with good publication practice (gpp 2022) guidelines (ann intern med. 2022;10.7326/m22-1460). these studies were funded by pfizer inc. previously presented at the 31st european academy of dermatology and venereology (eadv) hybrid congress; september 7-10, 2022; milan, italy. disclosures es received grants from pfizer inc., eli lilly and company, kyowa kirin, leo pharma, merck, and regeneron and personal fees from pfizer inc., bausch health (valeant), dermira, eli lilly and company, galderma, leo pharma, menlo therapeutics, novartis, regeneron, and sanofi genzyme. jis served as an investigator for celgene, eli lilly and company, f. hoffmann-laroche, menlo therapeutics, realm therapeutics, regeneron, and sanofi; as a consultant for pfizer inc., abbvie, anacor, anaptysbio, arena pharmaceuticals, dermavant, dermira, eli lilly and company, galderma, glaxosmithkline, glenmark, incyte, kiniksa pharmaceuticals, leo pharma, menlo therapeutics, novartis, realm therapeutics, regeneron, and sanofi; and as a speaker for regeneron and sanofi. an is an investigator for abbvie, eli lilly and company, incyte, leo pharma, novartis, and sanofi; a consultant for pfizer inc., abbvie, eli lilly and company, galderma, leo pharma, novartis, and sanofi; a speaker for abbvie, regeneron, and sanofi; and is on advisory boards for pfizer inc., abbvie, leo pharma, and sanofi. kw reports research grants from pfizer inc. and bristol myers squibb, and consulting fees from pfizer inc., abbvie, union chimique belge (ucb), eli lilly and company, galapagos, novartis, regeneron, sanofi, stiefel/glaxosmithklin, vitae, (honorarium);as a consultant for pfizer inc., abbvie, almirall (honorarium), anacor, asana biosciences, celgene, dermira, eli lilly and company, galderma, glenmark, kiowa kirin, leo pharmaceuticals, medimmune, mitsubishi tanabe, novartis, regeneron, sanofi, stiefel/glaxosmithklin, and vitae; and as an investigator for celgene, eli lilly and company (grants to institution), leo pharmaceuticals, medimmune, and regeneron. kmh received honoraria as consultant from pfizer inc. and platelet biogenesis. ae has received research funding from pfizer inc., abbvie, bristol-myers squibb, danish national psoriasis foundation, eli lilly and company, janssen pharmaceuticals, kgl hofbundtmager aage bang foundation, and novartis; and has received honoraria as a consultant and/or speaker from pfizer inc., abbvie, almirall, bristol-myers squibb, dermavant, eli lilly and company, galápagos nv, galderma, janssen pharmaceuticals, leo pharma, mylan, novartis, samsung bioepis co., ltd., sun pharmaceuticals, ucb, union therapeutics, and zuellig pharma ltd. hv was an employee and shareholder of pfizer, inc. at the time this analysis was conducted. hf, saf, gc, ja, wr, and sj are employees and shareholders of pfizer, inc. powerpoint-præsentation © mc2 therapeutics  1 phase 3 trial demonstrates that mc2-01 cream has improved treatment efficacy compared to calcipotriene plus betamethasone dipropionate topical suspension in patients with mild to moderate psoriasis vulgaris betamethasone diproponate (bdp) requires ph>8 for stability vitamin d analogue requires ph 4-6 for stability potent corticosteroid calcipotriene (cal)  dual additive efficacy of cal and bdp  improved safety profile compared to the individual actives alone ‒ bdp counteracts potential skin irritation of cal ‒ cal mitigates potential skin atrophogenic effect of bdp  pad™ technology uniquely enables stable aqueous cream combining cal and bdp 8 week treatment period 1x daily follow-up baseline week 8 screening adults mild to moderate psoriasis r mc2-01 cream (n=343) mc2-01 cream vehicle (n=115) cal/bdp topical suspension (n=338) 2 week followup figure 3: primary efficacy variable: % pga treatment successintroduction: mc2-01 cream is a novel topical treatment of psoriasis containing the active ingredients calcipotriene and betamethasone dipropionate (0.005% / 0.064% w/w, cal/bdp). mc2-01 cream is based on pad™ technology contributing high penetration of the actives combined with excellent cosmetic elegance. data from a phase 3 trial is presented comparing efficacy of mc2-01 cream to vehicle and to the comparator cal/bdp topical suspension (“cal/bdp ts”) in adults with mild to moderate psoriasis vulgaris on the body. the trial enrolled 796 patients at 55 clinical sites across the united states. methods: the phase 3, randomized, multicenter, investigator-blind, parallel-group trial evaluated the efficacy and safety of mc2-01 cream compared to mc2-01 vehicle and cal/bdp ts (sourced as taclonex® topical suspension) in adult patients with psoriasis vulgaris on the body. the 796 enrolled patients were distributed in three arms: mc2-01 cream (n=343), cal/bdp ts (n=338), mc2-01 vehicle (n=115). patients applied trial medication once daily for eight weeks. eligible patients were ≥18 years with a clinical diagnosis of psoriasis vulgaris of at least 6 months duration with mild-moderate disease severity according to the 5point physician’s global assessment (pga) scale, involving 2-30% body surface area (bsa) and with a mpasi of at least 2. the primary efficacy endpoint was the proportion of subjects with treatment success at week 8, defined as a minimum two-point decrease from baseline in pga score. table 1 demonstrates that patient demographics and baseline disease characteristics (itt population) were comparable across the treatment groups. johan selmer1, birgitte vestbjerg1, morten præstegaard1, linda stein gold2 1mc2 therapeutics, hørsholm, denmark; 2dermatology clinical research, henry ford health system, detroit, michigan 0 10 20 30 40 50 60 70 80 0 2 4 6 8 % c ha ng e in m pa si fr om b as el in e weeks **** **** **** *** mc2-01 cream n=342 cal/bdp ts n=337 mc2-01 vehicle n=115 total n=7941 mean age (sd) 52.0 (14.4) 52.8 (13.7) 50.4 (14.3) 52.0 (14.1) gender female male 40.6 59.4 34.4 65.6 38.3 61.7 37.7 62.3 race white black or african americans asian other 84.8% 9.6% 2.9% 2.4% 88.7% 5.9% 3.0% 2.4% 88.7% 9.6% 0.9% 0.9% 87.0% 8.2% 2.6% 2.2% duration of psoriasis years (sd) 17.7 (13.4) 15.0 (12.7) 16.3 (13.7) 16.3 (13.2) baseline pga mild (%) moderate (%) 19.9 80.1 16.9 83.1 17.4 82.6 18.3 81.7 baseline mean mpasi (sd) 7.3 (3.9) 7.7 (4.1) 7.1 (4.1) 7.4 (4.0) baseline mean bsa % (sd) 7.3 (6.0) 8.4 (7.0) 7.5 (6.1) 7.8 (6.5) table 1: summary of patient demographics and baseline disease characteristics (itt population) 0 10 20 30 40 50 0 2 4 6 8 % p g a t re at m en t su cc es s weeks **** **** **** primary objective:  non-inferiority of mc2-01 cream versus cal/bdp ts at week 8 using pga treatment success as primary endpoint primary analysis:  superiority versus mc2-01 vehicle was achieved  non-inferiority of mc2-01 cream versus cal/bdp ts was achieved  non-overlapping 95% ci demonstrated superiority of mc2-01 cream versus cal/bdp ts at week 8 mc2-01 cream (n=302) cal/bdp ts (n=279) mc2-01 vehicle (n=88) pga treatment success rate % (ci 95%) 40.1 (34.5 – 45.6) 24.0 (19.0 – 29.0) 4.5 (0.2 – 8.9) table 2: primary endpoint1 – pga treatment success at week 8 phase 3 trial met its primary objective and is superior to cal/bdp ts efficacy results: the phase 3 trial met its primary objective to demonstrate non-inferiority of mc2-01 cream to cal/bdp ts on pga treatment success at week 8 using the pp analysis set (table 2). the secondary efficacy endpoint of non-inferiority of % change in mpasi from baseline to week 8 of mc2-01 cream versus cal/bdp ts at week 8 was also met. additional analysis of pga treatment success on the itt population using multiple imputations showed that mc2-01 cream was superior to cal/bdp ts at week 4 (p<0.0001) and week 8 (p<0.0001) (fig. 3). similar analyses of % change in mpasi from baseline confirmed that mc2-01 cream was superior to cal/bdp ts throughout treatment from week 1 (26.2% vs. 18.9%, p<0.001) to week 8 (64.8% vs. 52.3%, p<0.0001) (fig. 4). mc2-01 cream provided robust reduction in itch vs. vehicle measured by the proportion of patients having ≥4-point improvement on an 11-point numeric rating scale of itch severity (60.2% vs. 21.4% at week 4, p<0.01) (fig. 5). 0 10 20 30 40 50 60 70 80 0 2 4 6 8 % ≥ 4po in t r ed uc tio n of n r s it ch weeks ** figure 4: secondary efficacy variable: % change from baseline in mpasi figure 5: secondary efficacy pro: reduction of itch by proportion of subjects with ≥4-point reduction of itch on 11-point nrs scale figure 2: phase 3 trial design safety data: no saes with relationship to study medication were observed in the trial. 3.5% of subjects in the mc2-01 cream arm had an ae definitely, probably, or possibly related to treatment compared to 3.3% of in the cal/bdp ts arm. the most frequent adverse events in both active arms were application site irritation, application site pruritus, and application site folliculitis; all with an occurrence below 1% in both arms. conclusion: mc2-01 cream demonstrated in the phase 3 trial a substantial improvement in overall efficacy and onset of action for topical treatment of psoriasis compared to cal/bdp ts without compromising the safety profile of the currently marketed cal/bdp fixed combinations. figure 1: rationale for mc2-01 cream ** p < 0.01 (mc2-01 vs mc2-01 vehicle) *** p < 0.001 (mc2-01 vs cal/bdp ts, post-hoc) **** p < 0.0001 (mc2-01 vs cal/bdp ts, post-hoc) **** p < 0.0001 (mc2-01 vs cal/bdp ts, post-hoc) mc2-01 cream cal/bdp ts mc2-01 vehicle mc2-01 cream cal/bdp ts mc2-01 vehicle mc2-01 cream cal/bdp ts mc2-01 vehicle 1.two patients (one in each active arm) were excluded from the itt population since they did not open the medication 1.the primary analysis for non-inferiority comparison was conducted on the per protocol analysis set slide number 1 previously presented at aad 2020presented at the 5th annual 2020 pa & np fall clinical dermatology conference, orlando, florida, november 13–15, 2020 objective • to assess the long-term efficacy of and durability of response to certolizumab pegol dosed at 400 mg every two weeks in patients with moderate to severe plaque psoriasis who achieve pasi 75 after an initial 16 weeks of treatment. outcomes • outcomes are reported for week 0 placebo-randomized patients who did not achieve pasi 50 at week 16, and entered the czp 400 mg q2w escape arm (weeks 16–144). • we report pasi 75, pasi 90, pga 0/1 and dermatology life quality index (dlqi) 0/1 responses to week 144. • missing data were imputed using markov chain monte carlo (mcmc) methodology. • responder rates reflect the simple average response and include patients who did and did not dose adjust during the open-label period. results • 116 placebo-randomized patients had a pasi <50 at week 16 and entered the czp 400 mg q2w escape arm. • baseline characteristics of included patients are shown in table 1. • patients demonstrated a rapid response during the first 16 weeks of czp 400 mg q2w treatment, with 74.7% achieving a pasi 75 response and 48.7% a pasi 90 response. – these responses were durable over 128 weeks of treatment: pasi 75 and pasi 90 responses were 75.5% and 57.6%, respectively, at week 144 (figure 2). • of the patients who achieved pasi 75 after 16 weeks’ czp treatment, 65.9% also achieved pasi 90. – after a further 128 weeks’ czp treatment, 82.4% of these patients maintained pasi 75 and 64.4% achieved pasi 90 (figure 2). • similar trends were reported for pga 0/1 (figure 3) and dlqi 0/1 (figure 4). background • certolizumab pegol (czp), an fc-free, pegylated anti-tumor necrosis factor (anti-tnf), has demonstrated efficacy and safety in moderate to severe plaque psoriasis (pso).1,2 methods study design • pooled data from the cimpasi-1 (nct02326298), cimpasi-2 (nct02326272), or cimpact (nct02346240) phase 3 studies are reported (figure 1). • patient inclusion criteria: – ≥18 years of age with pso for ≥6 months; – psoriasis area and severity index (pasi) ≥12; – ≥10% body surface area (bsa) affected; – physician’s global assessment (pga) ≥3 on a 5-point scale; – candidates for systemic pso therapy, phototherapy and/or photochemotherapy. references 1. gottlieb a.b. et al. jaad 2018;79:302–14.e6; 2. lebwohl m. et al. jaad 2018;79:266–76.e5. author contributions substantial contributions to study conception/design, or acquisition/analysis/interpretation of data: kg, rbw, abg, ab, dt, yp, mb, fb, ca, kr; drafting of the publication, or revising it critically for important intellectual content: kg, rbw, abg, ab, dt, yp, mb, fb, ca, kr; final approval of the publication: kg, rbw, abg, ab, dt, yp, mb, fb, ca, kr. author disclosures kg: honoraria and/or research support from abbvie, almirall, amgen, boehringer ingelheim, bristolmyers squibb, celgene, dermira inc., eli lilly, janssen, novartis, pfizer, sun pharma, and ucb pharma; rbw: research grants and/or consulting fees from abbvie, almirall, amgen, arena, avillion, bristolmyers squibb, boehringer ingelheim, celgene, eli lilly, janssen, leo pharma, novartis, pfizer, sanofi, ucb pharma; abg: current consulting/advisory board agreements with abbvie, avotres therapeutics, beiersdorf, boehringer ingelheim, bristol-myers squibb, celgene, eli lilly, incyte, janssen, leo pharma, novartis, sun pharma, ucb pharma, xbiotech; research and educational grants from boehringer ingelheim, incyte, janssen, novartis, ucb pharma, xbiotech; ab: served as a scientific adviser and/or clinical study investigator for abbvie, aclaris, allergan, almirall, athenex, boehringer ingelheim, bristolmyers squibb, dermavant, dermira, eli lilly and company, flx bio, forte, galderma, janssen, leo, novartis, ortho, pfizer, regeneron, sandoz, sanofi genzyme, sun pharma, and ucb pharma, and as a paid speaker for abbvie; dt: honoraria for participation on ad boards, as a speaker or for consultancy from abbvie, almiral, amgen, boehringer ingelheim, celgene, dignity, dr. reddy’s laboratories, galapagos, gsk, janssen, leo pharma, morphosis, msd, lilly, novartis, pfizer, sandoz-hexal, pfizer, regeneron/sanofi, ucb pharma; research grants from celgene and novartis; yp: investigator (research grants) from abbvie, baxter, boehringer ingelheim, celgene, centocor/janssen, eli lilly, emd serono, gsk, leo pharma, medimmune, merck, novartis, pfizer, regeneron, takeda, and ucb pharma; speaker (honoraria) from abbvie, celgene, janssen, eli lilly, leo pharma, novartis, regeneron, and sanofi genzyme; mb, fb, ca: employees of ucb pharma; kr: abbvie, affibody, amgen, biogen, boehringer ingelheim, celgene, centocor, covagen, forward pharma, gsk, janssen-cilag, kyowa kirin, leo pharma, eli lilly, medac, merck sharp & dohme corp., novartis, ocean pharma, pfizer, regeneron, samsung bioepis, sanofi, takeda, ucb pharma, valeant and xenoport. acknowledgments the studies were funded by dermira inc. in collaboration with ucb pharma. ucb is the regulatory sponsor of certolizumab pegol in psoriasis. we thank the patients and their caregivers in addition to the investigators and their teams who contributed to this study. the authors acknowledge susanne wiegratz, ucb pharma, monheim, germany for publication coordination and joe dixon, phd, costello medical, cambridge, uk for medical writing and editorial assistance. all costs associated with development of this poster were funded by ucb pharma. conclusions • czp dosed at 400 mg q2w offers a durable, long-term treatment option for patients with moderate to severe pso. durable efficacy of certolizumab pegol dosed at 400 mg every two weeks over 128 weeks in patients with plaque psoriasis enrolled in three phase 3 trials (cimpasi-1, cimpasi-2 and cimpact) k. gordon,1 r. b. warren,2 a. b. gottlieb,3 a. blauvelt,4 d. thaçi,5 y. poulin,6 m. boehnlein,7 f. brock,8 c. arendt,9 k. reich10,11 1department of dermatology, medical college of wisconsin, milwaukee, wi, usa; 2dermatology centre, salford royal nhs foundation trust, manchester nihr biomedical research centre, the university of manchester, uk; 3department of dermatology, icahn school of medicine at mount sinai, new york, ny, usa; 4oregon medical research center, portland, or, usa; 5institute and comprehensive center for inflammation medicine, university of lübeck, lübeck, germany; 6centre de recherche dermatologique du québec métropolitain, québec, canada; 7ucb pharma, monheim, germany; 8ucb pharma, slough, uk; 9ucb pharma, brussels, belgium; 10translational research in inflammatory skin diseases, institute for health services research in dermatology and nursing, university medical center hamburg-eppendorf; 11skinflammation® center, hamburg, germany acimpasi-1: nct02326298; cimpasi-2: nct02326272; cimpact: nct02346240; bloading dose of czp 400 mg q2w at week 0, 2, and 4; cdepending on pasi response, any dose adjustments were either mandatory or at the investigators discretion: bw: twice per week; czp: certolizumab pegol; etn: etanercept; ld: loading dose; pasi 50/75: 50%/75% improvement from baseline in psoriasis area severity index; q2w: every two weeks. adepending on pasi response, dose reductions to czp 200 mg q2w were permitted at the discretion of the investigator. czp: certolizumab pegol; pasi 75/90: 75/90% improvement from baseline in psoriasis area severity index; q2w: every two weeks. adepending on pasi response, dose reductions to czp 200 mg q2w were permitted at the discretion of the investigator. czp: certolizumab pegol; pga 0/1: physician’s global assessment score of 0 or 1 (“clear” or “almost clear”) with ≥2-point improvement from baseline; q2w: every two weeks. figure 1. study design of cimpasi-1 and 2 and cimpact cimpasi-1 and cimpasi-2a cimpacta figure 2. pasi 75 and pasi 90 responses to week 144 figure 3. pga 0/1 response to week 144 figure 4. dlqi 0/1 response to week 144 adepending on pasi response, dose reductions to czp 200 mg q2w were permitted at the discretion of the investigator. czp: certolizumab pegol; dlqi 0/1: dermatology life quality index of 0 or 1; no effect of disease on quality of life; pasi 75: 75% improvement from baseline in psoriasis area severity index; q2w: every two weeks. 0 16 4840 443212 36week 144 <pasi 50 – withdrawn etn 50 mg bw randomization re-randomization initial treatment period (double-blinded) maintenance period (double-blinded) 1:3:3:3 <pasi 50 – withdrawn <pasi 75 <pasi 75 <pasi 75 placebo q2w (n=57) open-label czp 400 mg q2w escape arm (n=53) washout ldb czp 200 mg q2w czp 400 mg q2w <pasi 75 only relevant treatment arms are shown open-label period czp 200 mg q2w possible dose adjustmentsc 0 randomization 1612week initial treatment period (double-blinded) 1:2:2 placebo q2w (n=100) ldb czp 200 mg q2w <pasi 50 <pasi 50 – withdrawn 4840 4432 36 maintenance period (double-blinded) <pasi 50 – withdrawn open-label czp 400 mg q2w escape arm (n=72) only relevant treatment arms are shown 144 open-label period czp 200 mg q2w possible dose adjustmentsc<pasi 50 <pasi 50 czp 400 mg q2w p la c e b o c z p 4 0 0 m g q 2 w p la c e b o placebo  czp 400 mg q2w (n=116) 74.7% 75.5% 48.7% 57.6% 0 16 32 48 64 80 96 112 r e sp o n d e r ra te i n a ll p a ti e n ts ( % ) 128 144 week pasi 75 responders after 16 weeks’ czp 400 mg q2w treatment (n=82) open-label period: 64/97 (66.0%) who entered this period remained on czp 400 mg q2wa 100.0% 82.4% 65.9% 64.4% pasi 75 pasi 90 0 16 32 48 64 80 96 112 r e sp o n d e r ra te i n p a s i 7 5 r e sp o n d e rs ( % ) 128 144 week open-label perioda 0 10 20 30 40 50 60 70 80 90 100 0 10 20 30 40 50 60 70 80 90 100 0 16 32 48 64 80 96 112 p g a 0 /1 r e sp o n se r a te i n a ll p a ti e n ts ( % ) 128 144 week open-label period: 64/97 (66.0%) who entered this period remained on czp 400 mg q2wa p g a 0 /1 r e sp o n se r a te i n p a s i 7 5 r e sp o n d e rs ( % ) open-label perioda 0 10 20 30 40 50 60 70 80 90 100 0 10 20 30 40 50 60 70 80 90 100 placebo  czp 400 mg q2w (n=116) pasi 75 responders after 16 weeks’ czp 400 mg q2w treatment (n=82) 65.4% 66.4% p la c e b o 81.7% 71.8% 0 16 32 48 64 80 96 112 128 144 week p la c e b o c z p 4 0 0 m g q 2 w p la c e b o c z p 4 0 0 m g q 2 w 0 16 32 48 64 80 96 112 d l q i 0 /1 r e sp o n se r a te i n a ll p a ti e n ts ( % ) 128 144 week open-label period: 64/97 (66.0%) who entered this period remained on czp 400 mg q2wa 0 10 20 30 40 50 60 70 80 90 100 placebo  czp 400 mg q2w (n=116) pasi 75 responders after 16 weeks’ czp 400 mg q2w treatment (n=82) p la c e b o 50.2% 59.2% d l q i 0 /1 r e sp o n se r a te i n p a s i 7 5 r e sp o n d e rs ( % ) open-label perioda 0 10 20 30 40 50 60 70 80 90 100 61.0% 68.0% 0 16 32 48 64 80 96 112 128 144 week placebo  czp 400 mg q2w (n=116) age (years), mean ± sd 46.4 ± 12.6 male, n (%) 76 (65.5) caucasian, n (%) 108 (93.1) weight (kg), mean ± sd 94.0 ± 26.1 duration of pso (years), mean ± sd 17.7 ± 12.1 concomitant psa,a n (%) 19 (16.4) pasi, mean ± sd 18.8 ± 6.7 bsa (%), mean ± sd 23.2 ± 13.9 pga score, n (%) 3: moderate 81 (69.8) 4: severe 35 (30.2) dlqi total score, mean (sd) 12.9 ± 7.4 any prior systemic therapy use for pso, n (%) 87 (75.0) prior biologic use, n (%) 33 (28.4) anti-tnf 19 (16.4) anti-il-17 12 (10.3) anti-il-12/il-23 6 (5.2) apresence of concurrent psa was self-reported. bsa: body surface area; czp: certolizumab pegol; dlqi: dermatology life quality index; il: interleukin; pasi: psoriasis area severity index; pga: physician’s global assessment; psa: psoriatic arthritis; pso: plaque psoriasis; q2w: every two weeks; sd: standard deviation; tnf: tumor necrosis factor. table 1. demographics and baseline characteristics of included patients patient perspectives on use of a water-based calcipotriene and betamethasone dipropionate cream formulation for the treatment of plaque psoriasis michael a. vecchiolla, bs,1 neal bhatia, md2 1epi health, llc, charleston, sc; 2therapeutics clinical research, san diego, ca references 1. carroll c, et al. br j dermatol. 2004;151(4):895-72. 2. feldman sr, et al. dermatol ther (heidelb). 2021;11(6):2077-88. 3. curcio a, et al. improving patient acceptability and adherence in psoriasis treatment. poster presented at the 42nd annual fall clinical dermatology conference®; october 20-23, 2022; las vegas, nv. 4. armstrong aw, read c. jama. 2020;323(19):1945-60. 5. wynzora. prescribing information. epi health; 2021. 6. praestegaard m, et al. dermatol ther (heidelb). 2022;12(10):2217-31. funding sources and disclosures the patient survey and poster development were funded by epi health, a novan company. dr. bhatia is a scientific advisor to epi health, and mr. vecchiolla is an epi health employee. • to assess patient satisfaction with cal/bdp cream applied once daily to affected areas • patients with plaque psoriasis strongly preferred a novel, water-based cal/bdp cream formulation to previously used prescription topical therapies • most patients reported the cal/bdp cream was well tolerated, moisturized plaques, and resulted in visible improvement within 1 week • rapid improvement may limit treatment discontinuation rates • tolerability of topical therapies is also particularly important as some surfactants cause skin irritation • a key benefit of the pad formulation used in wynzora cream is a reduced surfactant requirement compared to conventional emulsion systems presented at the 20th anniversary winter clinical dermatology conference – hawaii®; january 13–18, 2023; kohala coast, hawaii. synopsis • patient satisfaction with topical medications for the treatment of plaque psoriasis is directly related to adherence and real-world efficacy1 • poor cosmetic characteristics and the time-consuming nature of greasy topical agents cause up to 75% of patients to become nonadherent with topical psoriasis treatments2,3 • most patients have mild psoriasis that is amenable to topical therapies4 • wynzora® (calcipotriene [cal] and betamethasone dipropionate [bpd] 0.005%/0.064%) cream is a novel, moisturizing, water-based cream formulation5 – polyaphron dispersion (pad) technology allows formulation and efficient topical delivery of challenging molecules while maintaining a favorable aesthetic feel6 – suitable for psoriasis treatment on both body and scalp6 objective conclusions methods results • patient satisfaction data were collected using a 6-item survey about their experiences using the cream – included in new patient prescription kits – distributed by dermatology healthcare providers in november 2021 – completed 1 week after treatment initiation • patients responded using a 5-item likert scale (strongly agree, agree, neutral, disagree, strongly disagree) • survey results are based on the pooled number of strongly agree, agree, and neutral responses to each survey statement • 113 adults with plaque psoriasis completed surveys baseline characteristics patient perspectives figure 4. mean duration of cal/bdp cream use 10.4 days figure 1: psoriasis severity 44% (50/113) mild 45% (51/113) moderate 11% (12/113) severe figure 2: psoriasis treatment duration 59% (67/113) <1 year 41% (46/113) >1 year figure 3: first topical prescription medication for psoriasis 50% (57/113) cal/bdp cream 50% (56/113) othera • patient experiences with cal/bdp cream were positive 0 20 40 60 80 100 96% (108/113) 99% (112/113) patients (%) observed visible improvement in plaques in 1 week felt better/more confident about their plaque psoriasis preferred cal/bdp cream to other topical therapies used in the past 98% (111/113) reported it was non-greasy stated it helped moisturize their plaques reported treatment was well tolerated 95% (107/113) 96% (108/113) 98% (111/113) 96% (108/113) would recommend the cal/bdp creambased formulation aother therapies included topical steroids (n=46); generic calcipotriene/betamethasone (n=17); enstilar® foam (n=17); duobrii® lotion (n=15); topical steroids (n=46); taclonex® (n=10); calcipotriene (alone) (n=9); otezla® (n=5); infused biologics (n=3). n=38 torso, lower back, legs figure 6: locations of cal/bdp cream use n=20 scalp n=34 skinfolds around knees and/or elbows n=17 in between fingers or toes n=15 soles of feet and/or palms n=20 other figure 5. patient satisfaction survey results references 1. karia ps et al. j am acad dermatol. 2013;68:957–966. 2. stratigos aj et al. eur j cancer. 2020;128:60–82. 3. que skt et al. j am acad dermatol. 2018;78:237–247. 4. burova e et al. mol cancer ther. 2017;16:861–870. 5. regeneron pharmaceuticals, inc and sanofi-aventis us llc. libtayo® [cemiplimab-rwlc] injection full us prescribing information; 2021. available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761097s007lbl.pdf. accessed august 31, 2022. 6. european medicines agency. libtayo® epar; 2022. available at: https://www.ema.europa.eu/en/documents/product-information/libtayo-eparproduct-information_en.pdf. accessed august 31, 2022. 7. health canada. libtayo® notice of compliance with conditions qualifying notice; 2019. available at: https://www.canada.ca/en/health-canada/services/ drugs-health-products/drug-products/notice-compliance/conditions/libtayo-noticecompliance-conditions-218718.html. accessed august 31, 2022. 8. ministry of health israel. the israeli drug registry libtayo®; 2021. available at: https://mohpublic.z6.web.core.windows.net/israeldrugs/ rishum01_1_1299478321.pdf. accessed august 31, 2022. 9. stratigos aj et al. eur j cancer. 2020;128:83–102. 10. national comprehensive cancer network. national comprehensive cancer network clinical practice guidelines in oncology: squamous cell skin cancer (version 2.2022); 2022. available at: https://www.nccn.org/professionals/ physician_gls/pdf/squamous.pdf. accessed august 31, 2022. 11. rischin d et al. j immunother cancer. 2021;9:e002757. 12. migden mr et al. n engl j med. 2018;379:341–351. 13. migden mr et al. lancet oncol. 2020;21:294–305. 14. rischin d et al. j immunother cancer. 2020;8:e000775. presented at winter clinical derm 2023, january 13–18, 2023 (encore of previous presentation at the european society of medical oncology [esmo] 2022, september 8–13, migden mr et al.). reused with permission. conclusions • this final update to the empower-cscc-1 study confirms the efficacy, durability, and safety profile of cemiplimab in patients with advanced cscc. • no new safety concerns were identified on longer follow-up. • cemiplimab remains a standard-of-care option for metastatic or locally advanced cscc patients who are not candidates for curative surgery or radiation. table 3. teaes† teaes, n (%) advanced cscc, n=193 any grade grade ≥3 any 192 (99.5) 95 (49.2) serious 75 (38.9) 60 (31.1) leading to discontinuation 20 (10.4) 13 (6.7) leading to death 5 (2.6) 5 (2.6) occurring in ≥10% of patients (any grade) fatigue 67 (34.7) 5 (2.6) diarrhea 53 (27.5) 2 (1.0) nausea 46 (23.8) 0 pruritus 41 (21.2) 0 constipation 28 (14.5) 1 (0.5) vomiting 25 (13.0) 1 (0.5) arthralgia 34 (17.6) 1 (0.5) cough 32 (16.6) 0 rash 32 (16.6) 1 (0.5) anemia 22 (11.4) 8 (4.1) hypothyroidism 22 (11.4) 0 actinic keratosis 23 (11.9) 0 rash, maculo-papular 23 (11.9) 1 (0.5) upper respiratory tract infection 21 (10.9) 0 headache 21 (10.9) 0 †teaes occurring in ≥10% of patients are reported here. adverse events were coded according to the preferred terms of the medical dictionary for regulatory activities, version 22.1. the severity of adverse events was graded according to the national cancer institute common terminology criteria for adverse events, version 4.03. rti, respiratory tract infection; teae, treatment-emergent adverse event. introduction • cscc is the second most common malignancy in the usa, with approximately 186,000–420,000 cases diagnosed each year.1 • while most cases of cscc are cured by complete surgical excision, a small but substantial number of patients develop advanced disease, including locally advanced (lacscc) or metastatic (mcscc) disease.2,3 • cemiplimab is a high-affinity, fully human, hinge-stabilized, immunoglobulin g4 anti–programmed cell death-1 (pd-1) antibody that blocks the interaction of the pd-1 receptor with its ligands, pd-l1 and pd-l2.4 • cemiplimab is approved in the us and europe, and by multiple other health authorities, for the treatment of patients with metastatic or locally advanced cscc who are not candidates for curative surgery or curative radiation.5–8 additionally, cemiplimab is recommended for the treatment of patients with metastatic or locally advanced cscc not amenable to curative surgery or curative radiation by the european association of dermato-oncology, european organization for research and treatment of cancer, and the national comprehensive cancer network.9,10 • in the primary and follow-up analysis from the empower-cscc-1 phase 2 study, cemiplimab demonstrated substantial clinical benefit and an acceptable safety profile in patients with advanced cscc (nct02760498).11–14 – cemiplimab achieved an objective response rate (orr) of 46.1% in patients with advanced cscc, with complete response rates of 20.3%, 12.8%, and 16.1% for groups 1, 2, and 3, respectively.11 • here, we provide the final update from study groups 1, 2 and 3. objectives • primary objective: to assess the clinical benefits of cemiplimab as measured by orr (complete + partial response) per independent central review (icr). • key secondary objectives: duration of response (dor), progression-free survival (pfs), overall survival (os), complete response rate, and safety and tolerability. methods • empower-cscc-1 is an open-label, non-randomized, multicenter, international phase 2 study of patients with advanced cscc (nct02760498). • patients with histologically confirmed mcscc or unresectable lacscc received cemiplimab 3 mg/kg intravenous (iv) every 2 weeks for up to 96 weeks (group 1, mcscc; group 2, lacscc) or cemiplimab 350 mg iv every 3 weeks for up to 54 weeks (group 3, mcscc) (figure 1). • the data cutoff was march 1, 2022. results patients • a total of 193 patients were enrolled (group 1, n=59; group 2, n=78; group 3, n=56) with a median age of 72.0 years (range, 38–96). most patients had a primary cancer site of the head and neck (n=131, 67.9%) (table 1). • median duration of follow up was 15.7 months (range, 0.6–43.4) and median duration of exposure was 51.1 weeks (range, 2.0–109.3). response • tumor response per icr, median pfs and os remained generally consistent with the previous update (data cutoff: october 11, 2020) (table 2). • median pfs was 22.1 months (95% confidence interval [ci], 10.4–32.3) and the overall median dor was 41.3 months (95% ci, 38.8−46.3) (figures 2 and 3a). • median os was not reached. the kaplan–meier estimated probability of os at 48 months was 61.8% (95% ci, 54.0−68.7) (figure 3b). safety • all but one patient (n=192, 99.5%) experienced at least one treatment-emergent adverse event (teae) of any grade (table 3). • the most common teae of any grade was fatigue (n=67, 34.7%), followed by diarrhea (n=53, 27.5%), nausea (n=46, 23.8%), and pruritus (n=41, 21.2%). phase 2 study of cemiplimab in patients with advanced cutaneous squamous cell carcinoma (cscc): final analysis from empower-cscc-1 groups 1, 2, and 3 michael r migden,1 chrysalyne d schmults,2 nikhil i khushalani,3 alexander guminski,4 anne lynn s chang,5 karl d lewis,6 george ansstas,7 samantha bowyer,8 brett g hughes,9 dirk schadendorf,10 badri modi,11 lara a dunn,12 lukas flatz,13 axel hauschild,14 suk-young yoo,15 jocelyn booth,15 frank seebach,15 israel lowy,15 matthew g fury,15 danny rischin16 1departments of dermatology and head and neck surgery, university of texas md anderson cancer center, houston, tx, usa; 2department of dermatology, brigham and women’s hospital, harvard medical school, boston, ma, usa; 3department of cutaneous oncology, moffitt cancer center, tampa, fl, usa; 4department of medical oncology, royal north shore hospital, st leonards, new south wales, australia; 5department of dermatology, stanford university school of medicine, redwood city, ca, usa; 6university of colorado denver cancer center, aurora, co, usa; 7surgical oncology, washington university school of medicine, st louis, mo, usa; 8school of medicine and pharmacology, university of western australia, nedlands, western australia, australia; 9royal brisbane & women’s hospital and university of queensland, brisbane, queensland, australia; 10university hospital essen, essen and german cancer consortium, essen, germany; 11department of surgery, division of dermatology, city of hope, duarte, ca, usa; 12department of medicine, head and neck oncology, memorial sloan kettering cancer center, new york, ny, usa; 13university hospital tübingen, tübingen, germany; 14schleswig-holstein university hospital, kiel, germany; 15regeneron pharmaceuticals, inc., tarrytown, ny, usa; 16department of medical oncology, peter maccallum cancer centre, melbourne, victoria, australia table 1. patient demographics and baseline characteristics advanced cscc (n=193) age, years, median (range) 72.0 (38–96) male, n (%) 161 (83.4) ecog performance status, n (%) 0 86 (44.6) 1 107 (55.4) primary cscc site: head and neck, n (%) 131 (67.9) mcscc, n (%) 115 (59.6) lacscc, n (%) 78 (40.4) patients with cemiplimab as first-line therapy, n (%) 128 (66.3) patients with prior systemic therapy, n (%)† 65 (33.7) duration of exposure to cemiplimab, weeks, median (range) 51.1 (2.0–109.3) number of cemiplimab doses administered, median (range) 18.0 (1–48) †settings for prior lines of therapy included metastatic disease, adjuvant, chemotherapy with concurrent radiation, or other, and the most common types of prior systemic therapy were platinum compounds (n=46/65, 70.8%) and monoclonal antibodies (n=18/65, 27.7%). cscc, cutaneous squamous cell carcinoma; ecog, eastern cooperative oncology group; lacscc, locally advanced cutaneous squamous cell carcinoma; mcscc, metastatic cutaneous squamous cell carcinoma. table 2. tumor response per icr pd-l1 (22c3) group 1 (mcscc) 3 mg/kg q2w (n=59) group 2 (lacscc) 3 mg/kg q2w (n=78) group 3 (mcscc) 350 mg q3w (n=56) total (n=193) duration of follow-up, months, median (range) 18.5 (1.1–41.0) 15.5 (0.8–43.2) 17.3 (0.6–43.4) 15.7 (0.6–43.4) orr, % (95% ci) 50.8 (37.5–64.1) 44.9 (33.6–56.6) 46.4 (33.0–60.3) 47.2 (39.9–54.4) complete response, n (%) 12 (20.3) 10 (12.8) 11 (19.6) 33 (17.1) partial response, n (%) 18 (30.5) 25 (32.1) 15 (26.8) 58 (30.1) dor, months, median (95% ci) nr (20.7–ne) 41.9 (20.5–54.6) 41.3 (40.8–46.3) 41.3 (38.8–46.3) pfs, months, median (95% ci) 18.4 (7.3–53.2) 18.5 (11.1–43.8) 21.7 (3.8–43.3) 22.1 (10.4–32.3) os, months, median (95% ci) 57.7 (29.3–ne) nr (58.3–ne) 48.4 (29.5–ne) nr (56.0–ne) ci, confidence interval; dor, duration of response; icr, independent central review; lacscc, locally advanced cutaneous squamous cell carcinoma; mcscc, metastatic cutaneous squamous cell carcinoma; ne, not evaluable; nr, not reached; orr, objective response rate; os, overall survival; pfs, progression-free survival; q2w, every 2 weeks; q3w, every 3 weeks. group 1 – adults with metastatic (nodal and/or distant) cscc group 3 – adults with metastatic (nodal and/or distant) cscc group 2 – adults with locally advanced cscc cemiplimab 3 mg/kg q2w for up to 96 weeks† tumor imaging every 8 weeks for the assessment of clinical activity‡ tumor imaging every 9 weeks for the assessment of clinical activity tumor response assessment by an independent central review (icr) committee cemiplimab 350 mg q3w for up to 54 weeks key inclusion criteria key exclusion criteria • ecog performance status of 0 or 1 • adequate organ function • groups 1 and 3: – at least one lesion measurable by recist version 1.1 • group 2: – at least one lesion measurable by digital medical photography – cscc lesion that is not amenable to surgery or radiation therapy per investigators’ assessment • ongoing or recent (within 5 years) autoimmune disease requiring systemic immunosuppression • prior treatments with anti-pd-1 or anti-pd-l1 therapy • history of solid organ transplant, hematologic malignancies, or concurrent malignancies (unless indolent or not considered life threatening; e.g., basal cell carcinoma) figure 1. study design †retreatment optional for patients with disease progression during follow-up. ‡confirmatory scans performed no sooner than 4 weeks following initial documentation of tumor response. the severity of teaes was graded according to the national cancer institute common terminology criteria for adverse events (version 4.03). cscc, cutaneous squamous cell carcinoma; ecog, eastern cooperative oncology group; pd-1, programmed cell death-1; pd-l1, programmed cell death-ligand 1; q2w, every 2 weeks; q3w, every 3 weeks; recist 1.1, response evaluation criteria in solid tumors version 1.1; teae, treatment-emergent adverse event. p ro b a b ili ty o f p f s month mcscc cemiplimab: 3 mg/kg q2w lacscc cemiplimab: 3 mg/kg q2w mcscc cemiplimab: 350 mg q3w mcscc cemiplimab: 3 mg/kg q2w lacscc cemiplimab: 3 mg/kg q2w mcscc cemiplimab: 350 mg q3w 59 78 56 43 61 50 39 49 35 37 44 33 33 41 33 28 39 31 28 36 29 28 32 29 28 30 28 28 25 28 26 24 28 26 24 27 23 23 26 22 22 24 22 21 21 22 21 20 20 17 13 17 14 11 17 14 11 16 14 11 8 9 10 1 3 9 1 1 2 1 1 1 1 1 1 1 1 0 1 1 0 0 1 0 0 1 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1.0 a 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 54 56 58 60 62 64 66 68 70 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 p ro b a b ili ty o f o s month mcscc cemiplimab: 3 mg/kg q2w lacscc cemiplimab: 3 mg/kg q2w mcscc cemiplimab: 350 mg q3w mcscc cemiplimab: 3 mg/kg q2w lacscc cemiplimab: 3 mg/kg q2w mcscc cemiplimab: 350 mg q3w 59 78 56 56 76 52 52 73 49 49 67 46 47 65 45 47 65 44 46 64 38 41 62 38 39 59 38 39 55 37 38 53 37 38 53 35 37 51 34 35 47 32 34 47 31 33 46 30 33 45 29 31 44 28 29 43 27 29 43 27 29 43 27 29 41 27 29 36 26 29 33 21 28 30 17 28 23 5 28 22 1 27 19 0 23 13 0 16 9 0 12 5 0 3 4 0 1 2 0 0 0 0 0 0 0 0 0 0 1.0 b 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 54 56 58 60 62 64 66 68 70 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 number of subjects at risk number of subjects at risk figure 3. kaplan–meier curves of (a) pfs and (b) os cscc, cutaneous squamous cell carcinoma; icr, independent central review; lacscc, locally advanced cutaneous squamous cell carcinoma; mcscc, metastatic cutaneous squamous cell carcinoma; os, overall survival; pfs, progression-free survival; q2w, every 2 weeks; q3w, every 3 weeks. figure 2. kaplan–meier curves of dor per icr p ro b a b ili ty o f n o p ro g re s s io n o r d e a th month mcscc cemiplimab: 3 mg/kg q2w lacscc cemiplimab: 3 mg/kg q2w mcscc cemiplimab: 350 mg q3w number of subjects at risk mcscc cemiplimab: 3 mg/kg q2w lacscc cemiplimab: 3 mg/kg q2w mcscc cemiplimab: 350 mg q3w 30 35 26 30 33 26 29 32 26 28 31 25 24 29 23 24 27 23 23 24 23 23 23 22 23 19 22 21 19 22 20 18 21 18 16 19 18 16 17 18 15 15 18 14 14 17 11 10 13 11 9 13 11 9 12 10 7 9 6 5 0 2 5 0 1 1 0 1 1 0 1 1 0 1 0 0 1 0 0 1 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1.0 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 54 56 58 60 62 64 66 68 70 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 cscc, cutaneous squamous cell carcinoma; dor, duration of response; icr, independent central review; lacscc, locally advanced cutaneous squamous cell carcinoma; mcscc, metastatic cutaneous squamous cell carcinoma; q2w, every 2 weeks; q3w, every 3 weeks. disclosure michael r migden reports honoraria and travel expenses from regeneron pharmaceuticals, inc., sanofi, novartis, genentech, eli lilly, and sun pharma; and institutional research funding from regeneron pharmaceuticals, inc., novartis, genentech, and eli lilly. acknowledgments the authors thank the patients, their families, all other investigators, and all investigational site members who participated in this study. medical writing and editorial support under the direction of the authors was provided by sameen yousaf, phd, of prime (knutsford, uk) and funded by regeneron pharmaceuticals, inc., and sanofi according to good publication practice guidelines. responsibility for all opinions, conclusions and data interpretation lies with the authors. • grade ≥3 teaes were reported in 95 patients (49.2%). the most common grade ≥3 teaes were hypertension (n=9, 4.7%), cellulitis, and anemia (each n=8, 4.1%), pneumonia (n=8, 4.1%), pneumonitis (n=6, 3.1%), sepsis (n=5, 2.6%), and fatigue (n=5, 2.6%). • in total, 19 patients (9.8%) experienced at least one sponsor-identified grade ≥3 immune-related adverse event, the most common of which were pneumonitis (n=6, 3.1%), diarrhea, and autoimmune hepatitis (each n=2, 1.0%). • twenty patients (10.4%) discontinued treatment due to teaes of any grade (supplementary table 1). beyond what has previously been reported,6–8 no new teae-related deaths occurred. scan the qr code for supplementary material and co-author disclosures skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 37 brief articles tp53 mutated metastatic basal cell carcinoma responsive to sonidegib brian wanner, do1, austin cusick, bs2, jyoti kapil, md3, stephen d’addario, md1 1division of dermatology, ohiohealth riverside methodist hospital, grandview heights, oh 2ohio university heritage college of osteopathic medicine, athens, oh 3inform diagnostics, dermatopathology, irving, tx recent estimates report approximately 5.4 million cases of nonmelanoma skin cancer (nmsc) per year.1 basal cell carcinoma (bcc) is the most common nmsc, and the most common skin cancer overall. bcc is commonly linked directly to excessive sun exposure and considered to constitute 80% of nmscs.2 it has several histopathological presentations including nodular, superficial, infiltrative, and mixed subtypes.2 with respect to advanced cases, bcc tends to involve aggressive local invasion rather than distant site metastasis. distant metastasis, however, can occur, and has a reported prevalence of less than 0.55% of all bcc cases.2 tumor genetics play a significant role in the prognosis and subsequent treatment of metastatic bcc. we present the case of a 60-year-old male with tp53 mutated metastatic bcc responsive to sonidegib. a 60-year-old male with history of a left shoulder superficial bcc (status post electrodessication and curettage [ed&c] 10 years prior) presented with a four-centimeter subcutaneous nodule over the right clavicle (fig. 1). he was referred to dermatology after a previous biopsy of the lesion showed evidence of a cystic basal cell carcinoma. of note, a chest computed tomography (ct) scan prior to initial biopsy showed pulmonary nodules of minimal significance. no other concerning lesions were identified on full skin exam and his previous ed&c site had no evidence of recurrence. the abstract basal cell carcinoma (bcc) is the most common nonmelanoma skin cancer (nmsc) with the potential of local invasion and distant metastasis. our patient presented with an enlarging four-centimeter subcutaneous nodule over the right clavicle. an incisional biopsy demonstrated the unexpected findings of a nodular and infiltrative bcc. definitive treatment was a radical neck dissection with adjuvant radiation therapy. negative margins were confirmed on the excision and lymph node evaluation demonstrated no lymphatic spread. surveillance chest computed tomography revealed new bilateral pulmonary nodules and a subsequent biopsy showed metastatic bcc. a genetic panel demonstrated tp53 mutations and no mutations in smo. the patient was started on sonidegib and after ten months of therapy his disease was stabilized on repeat imaging. this case report demonstrates a rare presentation of a tp53 mutated, metastatic bcc responsive to sonidegib. introduction case presentation skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 38 patient was referred to a dermatologic surgeon for incisional biopsy which demonstrated basaloid cells with peripheral palisade, focal clefting, mucin deposition, large caliber perineural invasion, and extension to peripheral and deep tissue edges (figure 2a and 2b). the findings were consistent with bcc, nodular and infiltrative types. immunohistochemistry demonstrated weak berep4 expression (figure 3) and negative ck20 and ttf1. he was referred to an otolaryngologic surgeon for mass excision, neck dissection, and adjuvant radiation therapy. negative margins were confirmed on mass excision, and all 63 lymph nodes were negative for malignancy. surveillance chest ct revealed significant growth in previously described bilateral pulmonary nodules. biopsy of the right lung nodule revealed a non-small cell carcinoma with histopathological findings favorable of metastatic bcc. he was referred to medical oncology and started on sonidegib 200 mg daily with reduction to 6 days a week. subsequent genetic analysis revealed no mutation in smo, however, biallelic tp53 mutations were present. eight months after initiating sonidegib therapy, the patient complained of worsening muscle cramps which improved after decreasing sonidegib dosing to three times a week. ten months after starting therapy, chest ct scan ensured no further growth or increase in the number of lung nodules. in the described case, there was no evidence of a primary bcc despite several skin exams. due to his history of bcc on the left shoulder, metastasis from this lesion seems possible. however, with no evidence of recurrence at the ed&c site, metastasis from this area is uncertain. as present in this case, a common site of metastasis for bcc is the lungs.3 figure 1. metastatic bcc presenting as a subcutaneous nodule. advanced bcc can be described as either “locally advanced” (labcc) or “metastatic” (mbcc).4 labccs extend beyond the skin into the local tissue but do not extend far from the primary lesion. metastatic bcc is differentiated by noncontiguous spread to organs or structures distant from the primary lesion.4 the following factors have been associated with increased mortality and metastasis of bcc: tumors > 2cm, tumor depth beyond fat, perineural invasion, infiltrative type on histology, and location on the head and neck.5 with recent advances in the molecular understanding of mbcc, more information is available to determine likelihood of metastasis and response to treatment. currently, mutations in the ptch1 (produces patched) or smo (produces smoothened) genes of the hedgehog signaling pathway (hh) are known to lead to carcinogenesis.6 patched constantly inhibits smoothened preventing further transcription and translation of pathway end products. inactivating mutations of ptch1, or activating mutations of smo, create an unchecked formation of downstream products leading to bcc formation.6 the patient described above was negative for a discussion skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 39 smo mutation, but positive for biallelic tp53 mutations. ptch1 testing was not performed. figure 2: (a) hematoxylin and eosin stain showing nodular and infiltrative bcc (h&e, 20x) with (b) perineural invasion (h&e, 40x). the tumor suppressor gene tp53 can play a significant role in bcc formation. tp53 is considered the “guardian of the genome” and is the second most frequently mutated gene in bccs.6 interestingly, pelligreni et al. demonstrated loss of tp53 in murine models led to significant upregulation in the hh pathway, specifically in smo products (i.e. smoothened). consequently, the above patient’s successful response to sonidegib (a smoothened inhibitor) might be attributed to this pathway. unfortunately, testing for ptch1 was not performed for this patient. figure 3: immunohistochemical stains demonstrating weak expression of berep4 (berep4 stain, 40x) despite the efficacy of smoothened inhibitors, there are relevant adverse effects which commonly lead to treatment discontinuation. common side effects include muscle spasms, weight loss, dysgeusia, alopecia, and fatigue.7 mitigating these side effects while maximizing treatment potential is challenging. a recent study demonstrated reducing treatment frequency can lessen adverse effects and increase compliance.7 they demonstrated a 5-day dosing regimen with a weekend holiday can improve adverse effects and maintain successful treatment.7 similar findings were seen in our patient after adjusting treatment from 6 days a week to 3 days a week. in review, we present a case of a 60-yearold male with node-negative, metastatic bcc to the lungs. on genetic analysis, his tumor was positive for a tp53 mutation and negative for smo mutations. he has shown continued improvement on oral sonidegib three days a week. skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 40 limitations no epidemiological quantities can be generated from a single case report. additionally, the findings from a case report cannot be generalized and pose a risk for misinterpretation. this case is also hindered by a lack of testing for ptch1 gene mutations which could also explain the efficacy of sonidegib in this patient. abbreviation list bcc basal cell carcinoma nmsc non-melanoma skin cancer labcc locally advanced basal cell carcinoma mbcc metastatic basal cell carcinoma nscc non-small cell carcinoma hh hedgehog signaling pathway ptch1 patched 1 smo smoothen ed&c electrodessication and curettage conflict of interest disclosures: none funding: none corresponding author: brian wanner, do division of dermatology ohiohealth riverside methodist hospital 3535 olentangy river rd columbus, oh 43214 phone: 614-566-5456 fax: 470-275-0804 email: brian.wanner@ohiohealth.com references: 1. rogers hw, weinstock ma, feldman sr, coldiron bm. incidence estimate of nonmelanoma skin cancer (keratinocyte carcinomas) in the us population, 2012. jama dermatol. 2015;151(10):1081-1086. doi:10.1001/jamadermatol.2015.1187 2. piva de freitas p, senna cg, tabai m, chone ct, altemani a. metastatic basal cell carcinoma: a rare manifestation of a common disease. case rep med. 2017;2017:8929745. doi:10.1155/2017/8929745 3. seo s-h, shim w-h, shin d-h, kim y-s, sung hw. pulmonary metastasis of basal cell carcinoma. ann dermatol. 2011;23(2):213-216. doi:10.5021/ad.2011.23.2.213 4. fecher la, sharfman wh. advanced basal cell carcinoma, the hedgehog pathway, and treatment options role of smoothened inhibitors. biologics. 2015;9:129-140. doi:10.2147/btt.s54179 5. morgan fc, ruiz es, karia ps, besaw rj, neel va, schmults cd. factors predictive of recurrence, metastasis, and death from primary basal cell carcinoma 2cm or larger in diameter. journal of the american academy of dermatology. published online october 2019. doi:10.1016/j.jaad.2019.09.075 6. pellegrini c, maturo mg, di nardo l, ciciarelli v, gutiérrez garcía-rodrigo c, fargnoli mc. understanding the molecular genetics of basal cell carcinoma. int j mol sci. 2017;18(11). doi:10.3390/ijms18112485 7. wong c, poblete-lopez c, vidimos a. comparison of daily dosing vs. monday through friday dosing of vismodegib for locally advanced basal cell carcinoma and basal cell nevus syndrome: a retrospective case series. journal of the american academy of dermatology. published online february 21, 2020. doi:10.1016/j.jaad.2020.02.050 mailto:brian.wanner@ohiohealth.com https://doi.org/10.1001/jamadermatol.2015.1187 https://doi.org/10.1155/2017/8929745 https://doi.org/10.5021/ad.2011.23.2.213 https://doi.org/10.2147/btt.s54179 https://doi.org/10.1016/j.jaad.2019.09.075 https://doi.org/10.3390/ijms18112485 https://doi.org/10.1016/j.jaad.2020.02.050 microsoft word september 2020 rescomp 914 proof.docx skin september 2020 volume 4 issue 5 copyright 2020 the national society for cutaneous medicine 417 resident competition research articles the impact of skin disease on quality of life in rural communities of ghana caroline w. laggis, md1, aaron m. secrest, md, phd1,2, martin agyei, md3, sam simister, bs4, andera n. davis, phd5, ty dickerson, md, mph4, jamie l.w. rhoads, md, ms1 1department of dermatology, university of utah, salt lake city, ut, usa 2department of population health sciences, university of utah, salt lake city, ut, usa 3komfo anokye teaching hospital (kath), kumasi, ghana 4school of medicine, university of utah, salt lake city, ut, usa 5department of geography, university of utah, salt lake city, ut, usa the 2015 global burden of disease (gbd) reported that skin and subcutaneous disorders are the fourth leading cause of non-fatal disease burden worldwide, with dermatitis causing the greatest burden.1 the gbd provides valuable insight into the burden of skin disease over time and by abstract background: skin disease is the fourth-leading cause of non-fatal disability worldwide. granular data are limited on the skin disease burden in underserved populations. objectives: to describe the skin disease burden among adults in rural ghana. methods: in this observational study, 230 adults in rural ghana were surveyed using the dermatology life quality index (dlqi). for those reporting a skin problem in the previous week (n=117) and who had skin examination performed by a dermatology resident and/or local dermatologist (n=98), prevalence and univariate comparisons were calculated. results: 51% (117/230) of participants reported a skin problem in the previous week with 36% (42/117) reporting at least a moderate impact on quality of life (qol). factors associated with a higher qol impact included female gender (p=0.01) and living further from the city center (p=0.02). the most common dermatologic diagnoses for those with skin examination performed included acne, bacterial infection, and pruritus. qol was most impacted (highest average dlqi scores) for those with scabies. diagnoses were categorized by the level of treatment or medical expertise that would be required had the participant presented to a clinic. 80% (78/98) of diagnoses rendered were potentially manageable with counseling or topical medication. limitations: the studied cohort was obtained via convenience sampling. the dlqi has not yet been validated in this population. conclusions: much of the qol impact from skin disease among adults in rural ghana resulted from diagnoses that are manageable with counseling and topical medication. better access to basic health care and more dermatologic education among community health providers would address much of the skin disease burden in these communities. future studies should examine best practices for addressing unmet dermatologic needs of this and other comparable populations in underserved communities. introduction skin september 2020 volume 4 issue 5 copyright 2020 the national society for cutaneous medicine 418 geographic location, however, more granular data from rural communities in lowand middle-income countries (lmics) are limited.2 currently in ghana, fewer than 25 dermatologists are practicing3 in a country with a growing population of 28 million.4 in a referral center in urban accra, ghana, the most commonly-diagnosed skin conditions in adults were infections, dermatitis, acne vulgaris, and scabies.3 most ghanaian dermatologists, and general physicians, practice in urban centers, leaving residents living in rural communities to rely on the intermittent presence of physician assistants at clinic outposts for their health care needs.5 the dermatology life quality index (dlqi)6 is a 10-question dermatology-specific assessment of quality of life (qol) that has been translated and linguistically-validated in the ghanaian language of twi.7 dlqi has been used in previous studies in africa, but primarily in disease-specific qol studies.8-13 a large south african study, using a modified dlqi, explored the disability of skin disease in adults presenting to a dermatology clinic and found that social class and language influenced the dlqi scores.14 the current study aims to better understand the qol impact of skin disease in rural communities of the ashanti region of ghana in west africa. looking at dermatologic disease burden in specific communities brings attention to the spectrum of this burden across the geographic and economic spectrum. by better describing the burden of skin disease as it relates to demographic and diseaserelated factors in ghana, we are contributing to a collaborative response towards understanding and reducing the burden of skin disease in this and comparable lmics. the current project is a collaborative effort between the university of utah’s division of public health (dph) and department of dermatology with the komfo anokye teaching hospital (kath), kwame nkrumah university of science and technology (knust), and the atwima nwabiagya north district of the ashanti region near kumasi, ghana (figure 1). for the last decade, teams from university of utah’s dph have collaborated with kath and knust to conduct epidemiological studies in this region, steadily building a relationship of trust and comradery with the leaders and community members of the district. this study was approved by both the committee on human research, publications, and ethics of knust and kath and the university of utah institutional review board (irb 00111394). we developed a questionnaire to gather demographic data from adult participants. this questionnaire was tested for face validity and readability, then, along with the dlqi, was uploaded to digital tablets using ona software in both twi and english. the answer options to all dlqi questions are: (0) not at all; (1) a little; (2) a lot; and (3) very much. the final score (range 0-30) reflects the impact of an individual’s skin disease on qol: no effect on patient’s life (0-1); little effect (2-5); moderate effect (6-10); large effect (11-20); and extremely large effect (21-30). over a two-week period that included six field days, we surveyed participants in seven different rural and peri-urban communities (figure 1) in the atwima nwabiagya north district outside of the urban setting of kumasi, ghana, where there is a large teaching hospital and few dermatology methods skin september 2020 volume 4 issue 5 copyright 2020 the national society for cutaneous medicine 419 clinics. with the help of community liaisons and interpreters, research assistants solicited a convenience sample of adult individuals in the public market and residential areas to participate in a public health study regarding skin disease. the participants were recruited in a door-to-door fashion and were consented orally in their preferred language (twi or english) if they decided to participate. less than 10 individuals declined to participate. the research assistants read the questions out loud to participants then recorded their answers on the digital tablets. community liaisons helped explain questions when needed. individuals who responded positively to having a skin problem during the previous week received a specific identification number and were then privately examined by a dermatology resident and/or local dermatologist, often in the participants’ own homes. after obtaining additional permission, high-quality photographs were taken of relevant skin findings using a standardized background. two individuals refused to be photographed. while our role was primarily that of researchers, the dermatology resident (cwl) did offer medical advice to participants limited to diagnosis and medications that could be purchased safely over-the-counter. when the local dermatologist (ma) with a ghanaian medical license was present, he often prescribed medications. if the patient required dermatologic care beyond what was feasible at local medical clinics, we arranged followup with the local dermatologist to his clinic in kumasi. no participant required urgent medical attention. diagnoses were rendered on clinical appearance and history alone. skin problems were categorized by the dermatology resident and local dermatologist based on the american academy of dermatology’s burden of skin disease categories,15 with few adaptations to the categories (new categories added for “scabies” and “other”; categories for fungal infection and herpetic infection were separated). after the field days were complete, a board-certified dermatologist reviewed the photographs blinded to the diagnosis and also assigned a diagnostic category. any diagnostic discrepancies (<5%) were discussed and a consensus diagnostic category was reached. discrepancies primarily came from determining which of the participants skin problems shown in the photographs was their primary skin complaint for which they answered the survey questions. for example, in one case the participant was concerned about scarring, rather than acne, and this had to be clarified to the blinded dermatologist reviewing the photos. patient demographics were summarized by descriptive statistics (means with standard deviations and frequencies with percentages, as appropriate), overall and by disease burden using dlqi. differences were assessed using t-tests for continuous variables and chi-squared tests for nominal variables. all analyses were performed using sas software version 9.2, copyright march 2008, sas institute inc., cary, nc, and significance was considered as p < 0.05. demographics and dermatologic history over six field days, 230 adult participants were surveyed. participants were mostly female (157/230; 68%), with a mean age of 41.6 years, employed (166/230; 72%), married (111/230; 48%), and had completed primary school education (127/230; 55%). distances lived from the district’s major results skin september 2020 volume 4 issue 5 copyright 2020 the national society for cutaneous medicine 420 urban center ranged from 16.1 to 43.1 kilometers (km) (mean 25.3 km). based on survey answers, 51% (117/230) reported a skin problem in the previous week. dermatology life quality index (dlqi) results the dlqi was administered to all 230 participants who were surveyed. of the 113 who did not report a skin disease in the previous week, 100% (113/113) appropriately scored 0 points on the dlqi, which serves as a control group and helps validate this tool in this population. of those who reported a skin disease in the previous week, 30% (35/117) reported no effect on qol, 33% (39/117) reported a little effect, 19% (22/117) reported a moderate effect, 16% (19/117) reported a large effect, and 1.7% (2/117) reported an extremely large effect. among all participants, we compared those who reported little or no qol burden (dlqi£5, n=187) to those who reported moderate, large, or extremely large qol burden (dlqi>5, n=43) by demographic factors. age, employment, education or marital status were not associated with qol burden. females and those living further from the city center were more likely to report at least moderate skin disease burden (p£0.02). skin disease categories of the 117 participants who reported a current skin problem in the previous week, 98 had a skin exam performed, 18 left the study area before a skin exam was performed, and 1 refused a skin exam. the most common skin problems identified were acne (16%, 16/98), bacterial infection (14%, 14/98), pruritus (defined as participant itching without a rash) (12%, 12/98), benign neoplasms/scars/cysts (11%, 11/98), superficial fungal infections (10%, 10/98), eczema (8%, 8/98), hair and nail disorders (7%, 7/98), and scabies (5%, 5/98) (table 1). less frequent skin problems included seborrheic dermatitis, warts and molluscum, urticaria, herpes labialis, and ulcers. three patients reporting a skin problem in the previous week had resolution of their skin findings or symptoms at the time of the exam, thus no diagnosis could be rendered. although this study was not powered to detect any differences by skin disease category and qol burden, clear differences existed in burden for some disease categories (table 1). acne (mean dlqi 2.9) and benign neoplasms and scars (mean dlqi 3.2) were less burdensome overall than bacterial infections (mean dlqi 8.6), dermatitis (mean dlqi 8.8), and ulcers (mean dlqi 9.6). within our population, scabies infestation had the highest qol burden (mean dlqi 15.6). to provide a framework for skin disease severity, we categorized each participant’s diagnosis by the level of management that would be initiated had the participant presented to a dermatology clinic. treatment categories included counseling or reassurance, topical medication on the who essential medications list,16 oral medication on the who essential medications list, or additional diagnostic studies recommended (biopsy or culture). of the 98 participants with skin exams, 20% (20/98) could have been initially managed with counseling or reassurance, 59% (58/98) with a topical medication, and 6% (6/98) with an oral medication. 11% (11/98) of participant skin findings warranted an initial diagnostic evaluation with culture or biopsy (table 1). no trend in mean dlqi by management category existed. skin disease in rural ghana is common— 51% (117/230) of a convenience sample in a discussion skin september 2020 volume 4 issue 5 copyright 2020 the national society for cutaneous medicine 421 figure 1. map of communities around the atwima nwabiagya north district in the ashanti region outside of kumasi, ghana. distances are listed from each community to kumasi’s city center where the nearest dermatology clinics are located. mean distance = 25.3 kilometers (km). ghanaian community reported having a skin problem in the previous week. the most common diagnoses seen in our population were similar to those reported in the 2015 global burden of disease study,1 in the south african study,14 and in a retrospective study of the urban dermatology referral center in ghana.3 skin-related qol varied by gender in our cohort, with females endorsing a higher qol impact. women in rural ghana tend to work in and around the home, and many of their skin diagnoses were related to frequent exposure to water and cleaning chemicals (e.g., paronychia, acral candidal, contact dermatitis), which may contribute to this increased burden. participants who lived further from a dermatology clinic were more likely to have at least moderate qol impact from skin disease, suggesting that lack of access to care is a major obstacle to decreasing burden in underserved communities, and indeed remains a major barrier to providing adequate health care across all medical fields. innovations like teledermatology are lauded as possible solutions to bring dermatologic care to these underserved populations. while communities closer to kumasi had a clinic with infrastructure that could support teledermatology, even the most basic healthcare needs were not being met in more remote communities, including a functional health clinic with electricity and a reliable water source. meeting basic healthcare needs in rural ghana and other lmics should be prioritized before improving access to specialty care. eighty percent of the skin problems evaluated in this population could have been treated with counseling/reassurance or a skin september 2020 volume 4 issue 5 copyright 2020 the national society for cutaneous medicine 422 topical medication on the who essential medications list,16 and disease burden was not associated with treatment category. a recent study showed that training physician assistants in dermatology was an achievable method of expanding health care workers to rural populations in ghana.5 our study adds to the literature in that those with easily manageable skin conditions have a decreased qol because of their skin disease. this suggests that better dermatologic education and availability of physician assistants would likely meaningfully decrease skin disease burden in these rural communities. for example, our participants with scabies had the highest mean qol burden among all skin diagnoses made. anecdotally, individuals and their households in the most rural of these communities have either traditionally tried kerosene to ameliorate scabies infestations, or suffer for months to years with this condition. treatment of scabies with a topical scabicide and patient education performed by a trained physician assistant would be a welcome relief for the patients suffering from this curable condition. as our cohort was a convenience sample of adults in rural ghanaian communities, our prevalence figures are unlikely to be representative of the entire population. individuals with skin disease may have been more likely to participate in the study, leading to potential overestimations of the skin disease burden in this population. despite being a large study of skin disease impact on qol in rural africa, our study was insufficiently powered to perform skin disease-specific or multivariable analyses on factors associated with significant qol impact. the dlqi tool, while linguistically validated, was not validated in this specific population beyond efforts taken to ensure participant understanding and it was not tested for reliability by contacting participants after the study to retake the survey. we minimized the limitations of a dermatology resident’s diagnostic accuracy by involving a local dermatologist as frequently as possible and having an experienced board-certified dermatologist blinded to confirm diagnosis using highquality photographs. table 1. skin diseases by modified american academy of dermatology’s burden of skin disease category, management category, and associated quality of life (qol) burden as measured by the mean dermatology life quality index (dlqi). diagnostic categories (n=98) n (%) mean dlqi total 98 (100) 5.6 acne 16 (16.3) 2.9 bacterial infection 14 (14.3) 8.6 pruritus 12 (12.2) 5.3 benign neoplasm/scar/cyst 11 (11.2) 3.2 fungal 10 (10.2) 5.1 eczema/dermatitis 8 (8.1) 8.8 hair/nail disorders 7 (7.1) 4.7 scabies 5 (5.1) 15.6 other 4 (4.1) 3.5 ulcers 3 (3.1) 9.6 seborrheic dermatitis 2 (2.0) 5 human papilloma virus/molluscum 1 (1.0) 1 urticaria 1 (1.0) 3 herpes infection 1 (1.0) 0 no skin findings on exam 3 (3.1) n/a treatment categories (n=98) counseling/reassurance 20 (20.4) 4.0 topical treatment 58 (59.2) 8.4 oral treatment 6 (6.1) 2.8 needs biopsy, culture, or additional work-up 11 (11.2) 5.9 skin september 2020 volume 4 issue 5 copyright 2020 the national society for cutaneous medicine 423 adults in rural ghana commonly suffer from a skin disease that impacts their quality of life, the vast majority of which are not medically complicated dermatologic conditions, but rather from diagnoses that could be managed with education and topical therapies. this study emphasizes that providing access to basic dermatologic care would address the vast majority of the skin disease burden in this community. innovation and implementation of new technologies, while crucial in solving many public health problems, should not replace providing the most basic healthcare needs in underserved lowand middle-income communities. future studies should test best practices for addressing unmet dermatologic needs of this population and measuring the subsequent impact on quality of life. acknowledgements: we acknowledge dr. clive liu and dr. mark herron for their financial support of this research project through the university of utah resident alumni research fund. cwl expresses appreciation to drs. ty dickerson, scott benson, and rebecca buxton for the invitation to conduct this research project in the context of their long-standing relationships with the atwima nwabiagya north district, knust, and kath. we are grateful for the research assistants from knust, kath and the university of utah division of public health who administered the surveys. we would like to thank the community liaisons who assisted us on the ground in participant surveys. this investigation was supported by the university of utah population health research (phr) foundation, with funding in part from the national center for research resources and the national center for advancing translational sciences, national institutes of health through grant 5ul1tr001067-05 (formerly 8ul1tr000105 and ul1rr025764). dr. secrest is supported by a dermatology foundation public health career development award. a special thanks to nora fino, ms, for statistical support. conflict of interest disclosures: none funding: funding for this research came from an internal alumni research grant at the university of utah department of dermatology corresponding author: caroline w. laggis, md 30 north 1900 east, 4a330 salt lake city, utah 84132 phone: 843-870-1922 fax: 801-581-6484 email: caroline.laggis@hsc.utah.edu references: 1. karimkhani c, dellavalle rp, coffeng le, flohr c, hay rj, langan sm, et al. global skin disease morbidity and mortality: an update from the global burden of disease study 2013. jama dermatol. 2017;153(5):406-12. 2. seth d, cheldize k, brown d, freeman ef. global burden of skin disease: inequities and innovations. curr dermatol rep. 2017;6(3):204-10. 3. rosenbaum be, klein r, hagan pg, seadey my, quarcoo nl, hoffmann r, et al. dermatology in ghana: a retrospective review of skin disease at the korle bu teaching hospital dermatology clinic. pan afr med j. 2017;26:125. 4. central intelligence agency. ghana. in: the world factbook. washington, dc: central intelligence agency; 2015. accessed june 10, 2020 from https://www.cia.gov/library/publications/theworldfactbook/geos/gh.html. 5. truong a, cobb nm, hawkes je, adjase et, goldgar de, powell dl, et al. continuing dermatology education for rural physician assistants in ghana: an assessment of needs and effectiveness. j physician assist educ. 2018;29(1):19-24. 6. finlay ay, khan gk. dermatology life quality index (dlqi)--a simple practical measure for routine clinical use. clin exp dermatol. 1994;19(3):210-6. 7. ali f. quality of life questionnaires. accessed in october 2019 [available from: https://www.cardiff.ac.uk/medicine/resources/quality-of-lifequestionnaires]. 8. abdel-hafez k, mahran am, hofny er, mohammed ka, darweesh am, aal aa. the impact of acne vulgaris on the quality of life and psychologic status in patients from upper egypt. int j dermatol. 2009;48(3):280-5. 9. henok l, davey g. validation of the dermatology life quality index among patients with podoconiosis in southern ethiopia. br j dermatol. 2008;159(4):903-6. 10. khoudri i, lamchahab fz, ismaili n, senouci k, hassam b, abouqal r. measuring quality of life in patients with psoriasis using the arabic version for morocco of the dermatology life quality index. int j dermatol. 2013;52(7):795-802. 11. kiprono s, chaula b, makwaya c, naafs b, masenga j. quality of life of patients with vitiligo attending the regional dermatology training center in northern tanzania. int j dermatol. 2013;52(2):191-4. 12. klis s, ranchor a, phillips ro, abass km, tuah w, loth s, et al. good quality of life in former buruli ulcer patients with small lesions: long-term follow-up of the burolico trial. plos negl trop dis. 2014;8(7):e2964. 13. wiese s, elson l, feldmeier h. tungiasis-related life quality impairment in children living in rural kenya. plos negl trop dis. 2018;12(1):e0005939. 14. jobanputra r, bachmann m. the effect of skin diseases on quality of life in patients from different social and ethnic groups in cape town, south africa. int j dermatol. 2000;39(11):826-31. 15. lim hw, collins sab, resneck js, jr., bolognia jl, hodge ja, rohrer ta, et al. the burden of skin disease in the united states. j am acad dermatol. 2017;76(5):958-72 e2. 16. world health organization. 19th who model list of essential medicines. updated june 2019. available from: https://www.who.int/medicines/publications/essentialmedicines/en conclusion skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 275 brief articles why is my skin turning black? a rare side effect of capecitabine madeline adelman, bs1, jesse veenstra, md, phd2, ira wollner, md3, joseph mcgoey, md2 1wayne state university school of medicine, detroit, mi 2department of dermatology, henry ford health system, detroit, mi 3department of internal medicine, division of hematology and oncology, henry ford health system, detroit, mi capecitabine is an oral chemotherapy prodrug of 5-fluorouracil (5-fu) widely used in metastatic breast cancer and colorectal cancer treatment. capecitabine has an array of side effects, but the most common and potentially disabling is hand-foot syndrome (hfs), also called palmo-plantar erythrodysesthesia. few cases of capecitabine-induced hyperpigmentation have been reported, almost all of which were associated with hfs. we present a case of capecitabine-induced hyperpigmentation independent of hfs. an 82-year-old african american man presented for darkening of his hands, feet, and face after beginning adjuvant introduction case report introduction: capecitabine is an oral chemotherapy frequently used in the treatment of metastatic breast and colorectal cancers. drug-induced cutaneous hyperpigmentation is a rare adverse effect of capecitabine, which is almost exclusively reported with development of handfoot syndrome (hfs). here, we report a case of capecitabine-induced hyperpigmentation affecting the hands, feet, face, and tongue in the complete absence of hfs. case report: an 82-year old man presented with progressive hyperpigmentation of his hands, feet, face, and tongue shortly after initiating capecitabine for treatment of colon adenocarcinoma. there was no associated erythema, edema, blistering, desquamation, tingling, or tenderness. after completion of capecitabine therapy, he endorsed 95% resolution of all hyperpigmentation. discussion: previous reports of capecitabine-induced hyperpigmentation have argued that it may be a sign of impending toxicity and should be a part of the hfs grading scale. others argue that the two are separate entities, yet the mechanism is still unknown. this case supports that capecitabine can cause hyperpigmentation independent of hfs, and thus, should be evaluated as a separate entity of hfs if other symptoms are lacking. abstract skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 276 chemotherapy with capecitabine for colon adenocarcinoma. one to two weeks after starting therapy, he developed a prominent darkening of his palms and soles, which he was unable to remove with vigorous washing. the darkening was progressive, with a predilection for skin creases. within another week, he experienced similar generalized darkening on his face despite routine use of sunscreen. he also began to see multiple new “moles” under his eyes on a regular basis. he denied any associated redness, burning, blistering, tenderness, numbness, tingling, or other discomfort associated with the discoloration in the affected areas. his face had poorly-defined hyperpigmented patches, predominantly in the beard distribution along with scattered hyperpigmented macules below his eyes (figure 1). on the anterolateral aspects of his tongue were poorly-defined, mildly hyperpigmented gray/blue macules (figure 1). there were ill-defined darkly hyperpigmented patches on his palms and soles with accentuation in the palmar creases (figure 2). there was no associated erythema, edema, blistering, lichenification, desquamation, or tenderness with any of the lesions. the patient was counseled that this type of hyperpigmentation is a potential side effect of capecitabine therapy and would likely persist while he is on medication. after completing therapy, the hyperpigmentation slowly faded back to his normal skin tone. at approximately 10 months after discontinuation of capecitabine, he endorsed a 95% resolution of all hyperpigmentation. capecitabine is an oral antineoplastic agent converted to 5-fluorouracil (5-fu) by thymidine phosphorylase.1 5-fu and its derivatives have been associated with various types of hyperpigmentation, which occurs in up to 5% of patients;2-3 however, the mechanism remains largely unknown. previously reported patterns of hyperpigmentation include supravenous serpentine eruptions after peripheral venous administration of 5-fu2 and eruptive lentiginosis of the palms and soles.3 however, the most common cutaneous side effect of capecitabine is hand-foot syndrome (hfs), which manifests as dysesthesias and erythema that can progress to swelling, blisters, desquamation, and pain on the hands and feet.4 our patient presented with asymptomatic, rapid-onset hyperpigmentation involving the face, tongue, palms, and soles shortly after beginning capecitabine. while hyperpigmentation of acral skin is occasionally seen in association with hfs, it has very rarely been reported as an isolated side effect of capecitabine, especially with such robust hyperpigmentation as our patient exhibited. there are very few reports describing different patterns of capecitabine-induced hyperpigmentation in the literature. in the majority of these cases, hyperpigmentation was associated with the development of hfs and occurred in non-caucasian patients.1-8 vickers et al reported on 3 non-caucasian patients who developed hyperpigmentation of the palms and soles prior to severe hfs, and argued that hyperpigmentation may be a marker of hfs and impending toxicity.4 others have proposed that although the two entities may occur at the same time, they are separate syndromes with different mechanisms, though the mechanisms are still unclear.1 one case reported on an african american patient with marked hyperpigmentation not only of the hands and feet, but of the face and oral mucosa as well, suggesting hyperpigmentation may occur independently of hfs.1 discussion skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 277 there are currently only five reported cases of capecitabine-induced hyperpigmentation in absence of hfs symptoms. one reported on a 41-year old african american woman receiving capecitabine for ovarian carcinoma. figure 1. new onset hyperpigmented macules below the eyes (arrows) and lateral aspects of the tongue (arrow heads). figure 2. new onset hyperpigmented patches on the palms and soles. this patient developed hyperpigmentation of the palmar creases and soles, and patchy hyperpigmentation of the tongue, which resolved 8-10 days after treatment.5 in another case, a 59-year old middle eastern woman described similar findings of hyperpigmentation more apparent in the creases of her palms and soles, and well demarcated macules on the tongue.9 she had complete resolution of the lesions at 10 weeks after discontinuation of capecitabine. skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 278 while the majority of capecitabine-induced hyperpigmentation reports involve patients with darker skin, the last three cases of hyperpigmentation in the absence of hfs include patients with fairer skin. in all three, hyperpigmentation presented as macules confined to the sole of the foot.10,11 it is likely that this type of hyperpigmentation is common, yet underreported, especially in patients with darker skin types. overall, capecitabine is a well-tolerated and effective chemotherapeutic agent. this case, along with our prior experience, supports the idea that capecitabine-induced hyperpigmentation may occur as a distinct entity from hfs. there is no indication to alter dose or discontinue treatment upon the development of hyperpigmentation; however, it is important to advise patients to continue to monitor for changing symptoms indicative of hfs, such as edema, blistering, or desquamation. more research is required to help further understand the relationship between hyperpigmentation to capecitabine and other 5-fu derivatives and its underlying mechanism. conflict of interest disclosures: none funding: none corresponding author: jesse veenstra, md, phd 3031 w. grand blvd ste. 800, detroit, mi 48202 phone: 313-916-2151 fax: 313-916-5334 email: jjveenst1@gmail.com references: 1. caprez j, rahim u, ansari a, lodhi mu, rahim m. hyperpigmentation with capecitabine: part of hand-foot syndrome or a separate entity? cureus. 2018 mar 30;10(3):e2397 2. suvirya s, agrawal a, parihar a. 5-fluorouracilinduced bilateral persistent serpentine supravenous hyperpigmented eruption, bilateral mottling of palms and diffuse hyperpigmentation of soles. bmj case reports. 2014; 2014:bcr2014206793. doi:10.1136/bcr-2014206793. 3. bogenrieder t, weitzel c, schölmerich j, landthaler m, stolz w. eruptive multiple lentigomaligna-like lesions in a patient undergoing chemotherapy with an oral 5-fluorouracil prodrug for metastasizing colorectal carcinoma: a lesson for the pathogenesis of malignant melanoma? dermatology. 2002;205(2):174-5. 4. vickers mm, easaw jc. palmar-plantar hyperpigmentation with capecitabine in adjuvant colon cancer. j gastrointest cancer. 2008;39(14):141-3 5. verma p. capecitabine-induced acral and mucosal hyperpigmentation. indian journal of dermatology, venereology and leprology. 2017;83:583-583. 6. pui jc, meehan s, moskovits t. capecitabine induced cutaneous hyperpigmentation: report of a case journal of drugs in dermatology. 2002 sep;1(2):202-5. 1 7. villalon g, martin jm, pinazo mi, calduch l, alonso v, jorda e. focal acral hyperpigmentation in a patient undergoing chemotherapy with capecitabine. american journal of clinical dermatology. 2009;10:261263. 4 8. vasudevan b. an unusual case of capecitabine hyperpigmentation: is hyperpigmentation a part of hand-foot syndrome or a separate entity? indian journal of pharmacology. 2010;42:326-328. 8 9. j, z. and em, a. (2013). hyperpigmentation of the tongue, palms and soles: rare side effect of capecitabine. journal of cancer research & therapy, 1(10), pp.226-229. 10 10. tognetti l, fimiani m, rubegni p. benign dermoscopic parallel ridge pattern in plantar hyperpigmentation due to capecitabine. dermatology practical & conceptual. 2015;5:79. 11 11. peccerillo f, pampena r, giannetti l, pellacani g, longo c. capecitabine‐induced eruptive acral hyperpigmentation: clinical and dermoscopic evaluation of two cases. dermatologic therapy. 2019;32:e12853-n/a. 12 mailto:jjveenst1@gmail.com powerpoint presentation concordance of preferentially expressed antigen in melanoma by non-invasively collected polymerase chain reaction and immunohistochemistry on paraffin embedded tissue greg stevens dmsc pa-c1, burkhard jansen, md1, terry arnold, mba, pa-c1, james rock, ms1, jennifer wood, dmsc, pa-c1, mark hyde, phd, pa-c1, loren clarke, md1 1. dermtech, 11099 north torrey pines road, suite 150 la jolla, ca 92037, usa background: pigmented lesion evaluation remains a challenging aspect of dermatology. the dermtech melanoma test (dmt) is a non-invasive gene-expression test designed to rule-out melanoma. it consists of the pigmented lesion assay, which detects rna products of long intergenic non-coding rna 00518 (linc00518) and preferentially expressed antigen in melanoma (prame), and an add-on assay for dna promoter mutations in telomerase reverse transcriptase (tert). this registry study examines the concordance of prame detection by polymerase chain reaction (pcr) in samples obtained non-invasively prior to biopsy and prame detection by immunohistochemistry (ihc) on the same lesions after biopsy. methods: between april 2021 and march 2022, multiple geographically diverse sites throughout the us submitted data to a registry to assess real-world use of the dmt. approximately 8,000 clinically atypical lesions were tested. after receiving the test result, providers followed their clinical judgement for biopsy decision. when lesions expressed genomic markers (linc, prame, and/or tert) and were biopsied, pathology reports were also submitted to the registry. the presence or absence of prame by immunohistochemistry (ihc) was reviewed and compared to the detection of prame by pcr from the dmt on the same lesion. results: at the 1-year mark of the registry, there were roughly 8,000 unique entries. of those, 1,021 (12.8%) were positive for one or more of the dmt genomic markers. one thousand three lesions (98.2%) had records available. pathologists used prame ihc for 102 lesions (10.2%). of those, 40 (39.2%) were positive by ihc, and 62 (60.8%) were negative by ihc. prame positivity by pcr correlated with prame positivity by ihc in 35 of 40 lesions (87.5%). conversely, prame was detected using pcr in 28 of 62 lesions (45.2%) where it was not detected using ihc. conclusions: the higher sensitivity of pcr compared to ihc may explain the higher concordance when prame is positive by ihc than when it is negative by ihc. in this data set, when prame is positive by ihc it is usually also positive by pcr. when prame is negative by ihc, it can still be detected by pcr in a substantial percentage of cases. the increased sensitivity of pcr is likely due to several factors, including its detection of the prame mrna and sampling of the entire lesion. as such, prame pcr status may aid pathologists in understanding the risk of melanoma even when ihc is negative. further research is warranted to understand the clinical implications of prame pcr versus ihc positivity. abstract methods between april 2021 and march 2022, multiple geographically diverse sites throughout the us submitted approximately 8,000 clinically atypical lesions to a registry to assess real-world use of the dmt. providers then submitted pathology reports if biopsies were performed on lesions expressing one or more genomic markers (linc, prame, and/or tert.) pathology reports were individually reviewed for implementation of a prame immunohistochemistry (ihc) stain. when a stain was performed, its positivity or negativity was compared to the detection of prame by pcr from the dmt on the same lesion. furthermore, the histopathologic diagnoses of all lesions positive for prame by ihc were tabulated. there is a higher concordance with pcr when prame is positive by ihc than when it is negative by ihc. when prame is positive by ihc, it is usually also positive by pcr (87.5% concordance in this analysis). in contrast, the concordance rate when prame is negative by ihc is 54.8%. this suggests the dmt frequently detects prame expression that is below the level detectable by ihc. this difference in concordance rates may be explained by the higher sensitivity of pcr compared to ihc, due to several reasons. first, ihc detects the prame protein, and a relatively large number of the protein molecules must be present for staining to be detectable. in contrast, pcr detects prame mrna, and just one or two copies of prame rna can be detected by pcr. in addition, only a fraction of a biopsy lesion is examined by standard histopathology. prame expression is often heterogenous, and prame expression within the portion of a lesion examined by histopathology not be representative of the entire lesion. references results at the 1-year mark of the registry, there were roughly 8,000 unique entries. of those, 1,021 (12.8%) were positive for one or more of the dmt genomic markers. one thousand three lesions (98.2%) had records available. pathologists used prame ihc for 102 lesions (10.2%). of those, 40 (39.2%) were positive by ihc, and 62 (60.8%) were negative by ihc. table 1 shows concordance of prame by ihc and prame by pcr. table 2 shows the histopathological diagnoses of prame ihc-positive lesions. funding/disclaimer: all study sites were reimbursed by dermtech for the collection of data; the authors are employed by dermtech. conclusion scan qr code for additional peer-reviewed publications regarding this genomic test introduction and objective the gene expression test is designed to rule out melanoma by analyzing noninvasively collected skin tissue from pigmented lesions for genomic atypia (linc00518, prame, and/or tert). the results of the test are designed to guide biopsy decisions on clinically suspicious lesions. a negative result with no genomic biomarkers detected would lead to a recommendation of surveillance, while the presence of any biomarker would lead the provider to consider a surgical biopsy. this approach improves pigmented lesion management beyond visual inspection with a negative predictive value of ≥99% and a sensitivity of 91-97%, and by enriching melanoma among biopsied lesions almost 5-fold.1-3 dermatopathologists commonly use prame immunohistochemistry (ihc) stains to aid in the diagnosis of melanoma. this interim registry analysis examines the concordance of prame detection by polymerase chain reaction (pcr) in samples obtained non-invasively prior to biopsy and prame detection by ihc on the same lesions after biopsy. sdn = severely dysplastic nevus ajmh = atypical junctional melanocytic hyperplasia 1. gerami p, yao z, polsky d, et al. development and validation of a noninvasive 2-gene molecular assay for cutaneous melanoma. j am acad dermatol. 2017;76(1):114-120.e2. 2. jackson sr, jansen b, yao z, ferris lk. risk stratification of severely dysplastic nevi by non-invasively obtained gene expression and mutation analyses. skin the journal of cutaneous medicine. 2020;4(2):105-110. 3. brouha b, ferris lk, skelsey, mk, et al. genomic atypia to enrich melanoma positivity in biopsied lesions: gene expression and pathology findings from a large u.s. registry study. skin. 2021;5(1),13–18. furthermore, a prame ihc ‘result’ is a semi-quantitative interpretation of both the intensity and the extent of staining. in some cases, particularly when lesional cells are few in number, interpretation requires the judgement of the pathologist. presented at the winter clinical dermatology conference january 13-18, 2023 n % melanoma 26 65.0% melanoma in situ 17 42.5% invasive t1a 7 17.5% invasive t1b 2 5.0% non-melanoma 14 35.0% sdn/ajmh 8 20.0% mild/moderate dysplasia 5 12.5% normal melanocytic 1 2.5% table 2. histopathological diagnoses of 40 prame ihc-positive lesions table 1. concordance of prame by ihc and pcr n % ihc positive 40 39.2% pcr positive (concordance) 35 87.5% pcr negative (discordance) 5 12.5% ihc negative 62 60.8% pcr positive (discordance) 28 45.2% pcr negative (concordance) 34 54.8% slide number 1 powerpoint presentation efficacy and safety of tralokinumab treatment in adults of different racial subgroups with moderate-to-severe atopic dermatitis in three randomized, placebo-controlled phase 3 trials tiffany mayo1, april armstrong2, leon kircik3, jonathan i. silverberg4, andrew blauvelt5, ben esdaile6, shannon schneider7, thomas mark8, melinda gooderham9, andrew f. alexis10 1university of alabama at birmingham, birmingham, al, usa; 2keck school of medicine of university of southern california, los angeles, ca, usa;3icahn school of medicine at mount sinai, new york, ny, usa; 4the george washington school of medicine and health sciences, washington, dc, usa; 5oregon medical research center, portland, or, usa; 6whittington health national health service foundation trust, london, uk; 7leo pharma inc., madison, nj, usa; 8leo pharma a/s, ballerup, denmark; 9skin centre for dermatology, peterborough, on, canada; 10weill cornell medicine, new york, ny, usa table 1. baseline demographic and disease characteristics of patients by racial subgroup in pooled e1/2/3 table 2. summary of aes through week 16 in ecztra 1/2/3 by racial subgroup conclusions • in this post hoc analysis, tralokinumab was well-tolerated and improved the signs and symptoms of moderate-to-severe ad, regardless of race, with further improvements up to 52 weeks of treatment • limitations of this analysis include disparate sample sizes across racial subgroups tralokinumab improved signs and symptoms of ad across racial subgroups at week 16 • across three pooled trials at week 16, tralokinumab significantly improved efficacy outcomes in the asian and white subgroups relative to placebo. similar results were found in the smaller black subgroup, although statistical significance was not reached for all endpoints vs placebo (figures 2-3) • lower efficacy was observed for the black subgroup relative to asian and white subgroups when the monotherapy trials were pooled, driven by higher placebo response rates. in contrast, higher efficacy was observed for the black subgroup relative to asian and white subgroups in the tcs combination trial references 1. kaufman b, et al. exp dermatol 2018; 27: 340-357. 2. wollenberg a, et al. br j dermatol. 2021; 184(3)437-449. 3. silverberg j, et al. br j dermatol. 2021; 184(3)450-463 disclosures tiffany mayo has served as an investigator or consultant for eli lilly, chemocentryx, pfizer, janssen, galderma, bristol myers squibb, acelyrin, novartis, leo pharma, arcutis, and procter and gamble. april armstrong has served as a research investigator and/or scientific advisor to abbvie, almirall, arcutis, aslan, beiersdorf, bi, bms, epi, incyte, leo, ucb, janssen, lilly, nimbus, novartis, ortho dermatologics, sun, dermavant, dermira, sanofi, regeneron, pfizer, and modmed. leon kircik has served either as an investigator, consultant, or speaker for abbvie, almirall, amgen, arcutis, bausch health canada, bristol myers squibb, boehringer ingelheim, cellceutix, celgene, coherus, dermavant, dermira, eli lilly, leo, mc2, maruho, novartis, ortho dermatologics, pfizer, dr reddy's laboratories, sun pharma, ucb, taro, and xenoport. jonathan i silverberg reports honoraria as a consultant/advisory board member from leo pharma and has acted as a consultant for and/or received grants/honoraria from abbvie, anaptysbio, asana biosciences, galderma research and development, gsk, glenmark, kiniksa, leo pharma, lilly, medimmune, menlo therapeutics, pfizer, puricore, regeneron, and sanofi. andrew blauvelt has served as a speaker (received honoraria) for abbvie, arcutis, bristol-myers squibb, eli lilly and company, pfizer, regeneron, sanofi, and ucb, served as a scientific adviser (received honoraria) for abbvie, abcentra, affibody, aligos, almirall, alumis, amgen, anaptysbio, arcutis, arena, aslan, athenex, bluefin biomedicine, boehringer ingelheim, bristol-myers squibb, cara therapeutics, dermavant, ecor1, eli lilly and company, escient, evelo, evommune, forte, galderma, highlightii pharma, incyte, innoventbio, janssen, landos, leo, merck, novartis, pfizer, rapt, regeneron, sanofi genzyme, spherix global insights, sun pharma, tll pharmaceutical, trialspark, ucb pharma, vibliome, and xencor, and has acted as a clinical study investigator (institution has received clinical study funds) for abbvie, acelyrin, almirall, amgen, arcutis, athenex, boehringer ingelheim, bristol-myers squibb, concert, dermavant, eli lilly and company, evelo, evommune, galderma, incyte, janssen, leo, merck, novartis, pfizer, regeneron, sun pharma, and ucb pharma. ben esdaile has served either as an investigator, advisor or speaker for leo pharma, l’oréal, thornton & ross, bioderma, skin + me and abbvie. shannon schneider and thomas mark are employees of leo pharma. thomas mark owns leo pharma stock. melinda gooderham has been an investigator, speaker and/or advisor for: abbvie, amgen, akros, anaptysbio, aslan, arcutis, aristea, bausch health, bms, boehringer ingelheim, celgene, dermira, dermavant, eli lilly, galderma, gsk, incyte, janssen, kyowa kirin, leo pharma, medimmune, merck, meiji, moonlake, nimbus, novartis, pfizer, reistone, regeneron, roche, sanofi genzyme, sun pharma, and ucb. andrew f. alexis has received grants (funds to institution) from leo pharma, novartis, almirall, bristol myers squibb, amgen, vyne, galderma, valeant (bausch health), cara, arcutis, dermavant, abbvie, and castle; has served as an advisory board member or consultant for leo pharma, galderma, pfizer, sanofi-regeneron, dermavant, beiersdorf, ortho, l’oreal, bms, bausch health , ucb, vyne , arcutis, janssen, allergan, almirall, abbvie, sol-gel , amgen, visualdx, eli lilly, swiss american, and cutera; and a speaker for regeneron, sanofi-genzyme, pfizer, and bristol myers squibb. acknowledgements this analysis was sponsored by leo pharma a/s. medical writing according and editorial support from alphabet health by clair geary, phd was funded leo pharma a/s, ballerup, denmark, to good publication practice guidelines (https://www.ismpp.org/gpp3). this work was previously presented at fall clinical 2022. analyses • as shown in figure 1, data are presented as: o pooled from ecztra 1/2/3 o pooled from ecztra 1/2 o ecztra 3 • efficacy outcomes assessed were: o proportion of patients achieving easi-75, iga 0/1 o change from baseline in easi, peak pruritus nrs, dlqi, and poem • data are presented at week 16 (ecztra 1/2/3) and week 52 (ecztra 1/2) • data are presented as observed regardless of rescue medication use. multiple imputation was used for missing data • data were used as per food and drug administration (fda) label and united states prescribing information (uspi; i.e., data from 2 sites were excluded as per fda guidance) objective to evaluate the efficacy and safety of tralokinumab +/tcs versus placebo +/tcs, by self-identified racial subgroup (asian, black, white) in adults with moderate-to-severe ad across three phase 3 trials materials and methods patients and treatment • ecztra 1 and 2 were two identically designed, multinational, double-blind, randomized, placebo-controlled, 52-week trials (figure 1) o patients were randomized 3:1 to subcutaneous tralokinumab 300 mg or placebo every 2 weeks (q2w) for an initial 16 weeks following a 600 mg loading dose o patients who achieved iga 0/1 or easi-75 at week 16 with tralokinumab were rerandomized to tralokinumab q2w or every 4 weeks or placebo, for an additional 36 weeks o rescue treatment could be used at the discretion of the investigator to control intolerable symptoms • in ecztra 3, patients were randomized 2:1 to subcutaneous tralokinumab 300 mg + tcs as needed or placebo + tcs as needed q2w for an initial treatment period of 16 weeks following a 600 mg loading dose o patients who achieved iga 0/1 or easi-75 at week 16 with tralokinumab were rerandomized to tralokinumab q2w or every 4 weeks, with tcs as need, for an additional 16 weeks • patients self-reported their racial subgroup results patients, demographics, and clinical characteristics • this post hoc analysis included 1876 patients (uspi population) across ecztra 1, 2, and 3 who self-reported their race as asian, black, or white (figure 1, table 1) • baseline demographic and disease characteristics were largely balanced between treatment groups and across racial subgroups (table 1) o ad severity was more moderate in the black subgroup introduction • atopic dermatitis (ad) is a chronic inflammatory skin disease associated with significant disease burden • although ad is highly prevalent in patients with skin of color, data on the efficacy and safety of ad therapies in these patients is limited since most clinical trials enroll predominately white patients1 o several standard measures, including easi, can underestimate ad severity in dark skin1 • tralokinumab, a specific, high-affinity interleukin-13 inhibitor, is approved in europe, canada, and the united states for the treatment of adults with moderate-to-severe ad • ecztra 1 (nct03131648), ecztra 2 (nct03160885), and ecztra 3 (nct03363854) were randomized phase 3 trials assessing the safety and efficacy of tralokinumab or tralokinumab + tcs, as needed. o ecztra 1 and 2 were placebo-controlled trials and ecztra 3 was placebo + tcs controlled improvements in efficacy outcomes beyond week 16 were consistent across racial subgroups • at week 52 (pooled monotherapy trials), easi-75 was achieved in 58% of asian patients, 66% of black patients, and 63% of white patients (figure 4) o iga 0/1 was achieved in 32% of asian patients, 38% of black patients, and 38% of white patients (figure 4) • improvements in efficacy outcomes after week 16 were also observed across racial subgroups in ecztra 3 (tcs combination trial) abbreviations adj., adjusted; ae, adverse event; ad, atopic dermatitis; dlqi, dermatology life quality index; e, number of adverse events; easi, eczema area and severity index; iga, investigator’s global assessment; n, number of patients achieving the indicated metric, or with ≥1 event; ne, number of events; np, number of patients, n, number of patients with recorded observation; nrs, numerical rating scale; pye, patient-years of exposure; q2w, every 2 weeks; sd, standard deviation; tcs, topical corticosteroids asian n=407 black n=134 white n=1335 tralokinumab (n=291) placebo (n=116) tralokinumab (n=95) placebo (n=39) tralokinumab (n=992) placebo (n=343) mean age, y (sd) 35.2 (12.3) 32.4 (13.2) 39.3 (14.1) 38.6 (16.8) 39.0 (14.8) 38.7 (14.6) male, n (%) 176 (60.5) 76 (65.5) 38 (40.0) 20 (51.3) 578 (58.3) 209 (60.9) ethnicity, n (%) hispanic or latino 2 (0.7) 3 (2.6) 3 (3.2) 0 68 (6.9) 26 (7.6) region, n (%) north america europe australia japan asia 100 (34.4) 20 (6.9) 17 (5.8) 96 (33.0) 58 (19.9) 48 (41.4) 10 (8.6) 7 (6.0) 31 (26.7) 20 (17.2) 86 (90.5) 8 (8.4) 1 (1.1) 36 (92.3) 3 (7.7) 284 (28.6) 640 (64.5) 68 (6.9) 89 (25.9) 233 (67.9) 21 (6.1) country, n (%) united states canada japan 43 (14.8) 57 (19.6) 96 (33.0) 23 (19.8) 25 (21.6) 31 (26.7) 82 (86.3) 4 (4.2) 35 (89.7) 1 (2.6) 178 (17.9) 106 (10.7) 52 (15.2) 37 (10.8) patients with iga 3, n (%) 138 (47.4) 53 (45.7) 61 (64.2) 23 (59.0) 507/1001 (50.6) 169/346 (48.8) patients with iga 4, n (%) 153 (52.6) 63 (54.3) 33 (34.7) 15 (38.5) 490/1001 (49.0) 175/346 (50.6) mean easi (sd), n 33.2 (15.1) 34.1 (14.2) 29.2 (13.0), 94 33.1 (15.8), 38 31.5 (13.4), 997 31.9 (13.3), 344 mean scorad score (sd) 70.7 (14.7) 71.4 (12.4) 66.4 (12.4), 94 67.6 (12.7), 38 69.7 (12.8), 997 70.8 (12.8), 344 mean dlqi (sd), n 17.5 (7.1), 289 18.0 (6.6), 114 16.9 (7.1), 94 17.2 (9.7), 37 17.3 (7.0), 984 17.4 (6.9), 342 mean worst pruritus nrs (sd), n 7.8 (1.4), 288 7.8 (1.4), 116 8.1 (1.6), 94 7.7 (1.7), 37 7.7 (1.5), 991 7.9 (1.4), 342 asian black white tralokinumab (n=292) placebo (n=115) tralokinumab (n=94) placebo (n=38) tralokinumab (n=989) placebo (n=340) pye 86.93 33.60 26.92 10.74 294.47 99.54 n (%) rate (ne/100 pye) n (%) rate (ne/100 pye) n (%) rate (ne/100 pye) n (%) rate (ne/100 pye) n (%) rate (ne/100 pye) n (%) rate (ne/100 pye) all aes 197 (67.5) 570.5 79 (68.7) 633.9 52 (55.3) 542.3 25 (65.8) 512.1 713 (72.1) 753.2 243 (71.5) 772.5 serious aes 6 (2.1) 6.9 1 (0.9) 2.9 2 (2.1) 7.4 3 (7.9) 27.9 25 (2.5) 8.8 13 (3.8) 17.0 severity 161 (55.1) 424.4 61 (53.0) 455.3 45 (47.9) 408.6 17 (44.7) 316.5 590 (59.7) 500.9 181 (53.2) 412.9 mild moderate 76 (26.0) 132.2 42 (36.5) 157.7 19 (20.2) 122.5 13 (34.2) 167.6 362 (36.6) 224.4 149 (43.8) 311.4 severe 11 (3.8) 13.8 5 (4.3) 20.8 3 (3.2) 11.1 2 ( 5.3) 27.9 56 (5.7) 27.8 31 (9.1) 48.2 leading to withdrawal from trial 7 (2.4) 8.0 5 (4.3) 17.8 5 (5.3) 26.0 1 (2.6) 9.3 20 (2.0) 8.1 8 (2.4) 11.0 outcome not recovered/not resolved 39 (13.4) 65.5 18 (15.7) 65.4 14 (14.9) 55.7 7 (18.4) 74.4 156 (15.8) 70.3 43 (12.6) 60.2 recovering/resolving 16 (5.5) 18.4 8 (7.0) 23.8 7 (7.4) 26.0 41 (4.1) 15.6 21 (6.2) 26.1 recovered/resolved 179 (61.3) 483.1 68 (59.1) 544.6 49 (52.1) 445.7 22 (57.9) 428.3 668 (67.5) 655.4 233 (68.5) 680.1 recovered/resolved with sequelae 3 (1.0) 3.4 1 (1.1) 3.7 14 (1.4) 4.7 2 (0.6) 3.0 unknown 2 (2.1) 11.1 1 (2.6) 9.3 20 (2.0) 7.1 3 (0.9) 3.0 asian black white tralokinumab q2w (n=292) placebo (n=115) tralokinumab q2w (n=94) placebo (n=38) tralokinumab q2w (n=989) placebo (n=340) n (%) rate (ne/100 pye) n (%) rate (ne/100 pye) n (%) rate (ne/100 pye) n (%) rate (ne/100 pye) n (%) rate (ne/100 pye) n (%) rate (ne/100 pye) all aes 197 (67.5) 570.59 79 (68.7) 633.90 52 (55.3) 542.36 25 (65.8) 512.12 713 (72.1) 753.21 243 (71.5) 772.59 infections and infestations 87 (29.8) 141.50 40 (34.8) 196.42 27 (28.7) 133.73 12 (31.6) 139.67 446 (45.1) 237.71 145 (42.6) 232.08 viral upper respiratory tract infection 28 (9.6) 35.66 9 ( 7.8) 29.76 8 (8.5) 37.15 4 (10.5) 46.56 191 (19.3) 80.14 55 (16.2) 72.34 conjunctivitis 5 (1.7) 5.75 1 ( 0.9) 2.98 3 (3.2) 14.86 1 (2.6) 9.31 79 ( 8.0) 31.24 9 (2.6) 9.04 upper respiratory tract infection 17 (5.8) 21.86 6 ( 5.2) 20.83 3 (3.2) 11.14 2 (5.3) 18.62 60 (6.1) 22.07 15 (4.4) 15.07 skin infection 2 (0.7) 3.45 2 ( 1.7) 5.95 1 (1.1) 3.71 1 (2.6) 9.31 14 (1.4) 5.09 10 (2.9) 10.05 herpes simplex 5 (1.7) 8.05 1 ( 0.9) 2.98 1 (1.1) 3.71 17 (1.7) 6.45 4 (1.2) 5.02 figure 3. change from baseline in easi, itch, poem, and dlqi by racial subgroup at week 16 30 20 10 0 change from baseline 6 4 2 0 2 change from baseline 20 15 10 5 0 change from baseline 20 15 10 5 0 change from baseline easi itch poem dlqi asian; tralokinumab asian; placebo black; tralokinumab black; placebo white; tralokinumab white; placebo ecztra 1+2+3 ecztra 1+2 ecztra 3 table 3. summary of selected aes by soc and preferred term through week 16 in ecztra 1/2/3 by racial subgroup figure 1. summary of tralokinumab ecztra trials included in these analyses 52 weeks ecztra 1 tralokinumab monotherapy trials tralokinumab + tcs combination trial 32 weeks ecztra 1+2+3 pooled ecztra 1+2 pooled ecztra 3 only ecztra 3 selfreported raceecztra 2 asian (n=407) black (n=134) white (n=1335) further details of these trials have been previously reported2,3 asian (n=366) black (n=99) white (n=1059) asian (n=41) black (n=35) white (n=276) ecztra 1 (n=802) ecztra 2 (n=794) ecztra 3 (n=380) total randomized ecztra 1 (n=798) ecztra 2 (n=770) ecztra 3 (n=368) uspi population week 16 error bars show standard error. scan to download a copy of this poster copies of this poster and its content, obtained through this qr code, are for personal use only and may not be reproduced without written permission from the authors the safety profile of tralokinumab treatment was consistent across racial subgroups • tralokinumab was generally well-tolerated, with a safety profile comparable to placebo and largely consistent across racial subgroups (table 2) • rates of adverse events (aes), serious aes, and aes leading to drug withdrawal were low in all treatment groups • conjunctivitis rates were lower in the asian and black relative to white subgroup (table 3) figure 4. percentage of patients achieving easi-75 and iga 0/1 by racial subgroup at week 52 (pooled monotherapy trials) week 52 (ecztra 1+2) easi75 iga 0 / 1 0 20 40 60 80 63 38 66 38 58 32 r e s p o n d e rs , % asian black white figure 2. percentage of patients achieving easi-75 and iga 0/1 by racial subgroup at week 16 asian; tralokinumab black; tralokinumab white; tralokinumab asian; placebo black; placebo white; placebo ecztra 1+2+3 ecztra 1+2 ecztra 3 0 20 40 60 80 responders, % 0 10 20 30 40 50 responders, % easi75 iga 0/ 1 https://www.ismpp.org/gpp3 slide 1: efficacy and safety of tralokinumab treatment in adults of different racial subgroups with moderate-to-severe atopic dermatitis in three randomized, placebo-controlled phase 3 trials skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 681 research letter perspectives on pediatric hidradenitis suppurativa care: a survey of pediatric providers rahul masson, bs1, terri shih, bs2, devea r. de, bs3, swetha atluri, bs4, shahram yazdani, md5, christopher j. sayed, md6, vivian y. shi, md7, jennifer l. hsiao, md8 1 keck school of medicine of usc, university of southern california, los angeles, ca 2 david geffen school of medicine, university of california los angeles, los angeles, ca 3 university at buffalo, jacobs school of medicine and biomedical sciences, buffalo, ny 4 university of arizona college of medicine, tucson, az 5 division of general pediatrics, university of california los angeles, los angeles, ca 6 department of dermatology, the university of north carolina at chapel hill, chapel hill, nc 7 department of dermatology, university of arkansas for medical sciences, little rock, ar 8 department of dermatology, university of southern california, los angeles, ca hidradenitis suppurativa (hs) is a progressive inflammatory skin condition.1 studies have found that up to 50% of hs patients have symptom onset between 10-21 years.2 however, there is a paucity of data regarding pediatric providers’ perspectives on hs care. herein, we characterized the abstract background: hidradenitis suppurativa, or hs, is a chronic, inflammatory skin condition characterized by abscesses, nodules, and fistulas typically in intertriginous areas of the body. pediatric providers are key front-line providers for children and adolescents with hs, yet little is known about their diagnostic and management approach. objective: in this survey study, we elicited the perspectives and experiences of pediatric providers regarding hs care. methods: an anonymous survey was distributed to pediatric providers through online pediatric organizational listservs. survey questions addressed providers’ perspectives on hs diagnosis and management. comparative statistics between survey responses and provider experience were performed using t-tests and a p-value <0.05 was considered significant. results: among the 50 respondents, less than one-half were confident in knowing the available treatment options for hs (46%), managing mild hs (42%) or moderate-severe hs (6%), knowing pediatric hs comorbidities (30%), addressing challenges that hs patients face in school (22%), knowing when to discuss surgical treatments (20%), managing menstrual hs flares (14%), discussing the impact of hs on sexual health (14%), and managing patients with non-prescription therapies (0%). of the 25 participants who saw patients with hs, less than two-thirds “often/sometimes” screened for substance abuse (64%), polycystic ovarian syndrome (60%), premature adrenarche (28%), and inflammatory bowel disease (20%). conclusion: educational resources targeted towards pediatric providers and increased collaboration with dermatologists may improve hs care for children and adolescents. introduction skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 682 perspectives and experiences of pediatric providers on hs diagnosis and management to identify any knowledge and practice gaps. an anonymous survey was distributed with permission from may-september 2022 through online pediatric organizational listservs. t-tests were used for comparative statistical analyses between survey responses and provider experience (number of hs patients seen monthly and number of years in practice). significance was determined at a p-value <0.05. only 50% (n=25) of the 50 respondents reported seeing any hs patients in their practice, at an average rate of 1.4 patients per month (standard deviation 0.6, range 13) (table 1). providers’ perspectives on hs care are highlighted in figure 1. of the 25 respondents who saw hs patients, the majority often/sometimes screened for obesity (96%), mental health comorbidities (84%), hypertension (80%), diabetes (72%), hyperlipidemia (72%), substance abuse (64%) and polycystic ovarian syndrome (pcos) (60%). less than one-third screened for premature adrenarche (28%) and inflammatory bowel disease (20%). top treatments prescribed often/sometimes included topical (88%) and oral (80%) antibiotics. less than half often/sometimes prescribed oral contraceptives (48%), oral retinoids (20%), and spironolactone (12%); none often/sometimes prescribed biologics, cyclosporine, or methotrexate. similarly, a minority of the 25 respondents often/sometimes performed incision and drainage (16%) and deroofing procedures (4%); none often/sometimes performed intralesional steroid injections or wide local excisions. the majority of the 25 respondents often/sometimes referred patients to dermatologists (96%) followed by nutritionists (48%), mental health specialists (44%), general surgery (40%), endocrinology (16%), obstetrics/gynecology (16%), hs support groups (12%), plastic surgery (8%), infectious disease (4%), and pain management (0%). most of the 50 respondents strongly/somewhat preferred internet-based medical education resources (100%), peer-reviewed papers (96%), and podcasts or webinars (72%) to learn more about hs, while a minority preferred conferences (40%) and textbooks (26%). providers who saw ≥2 hs patients per month were more confident in diagnosing hs (p=0.019), knowing the available treatments (p=0.001), and managing mild hs (p=0.01) compared to those who saw fewer patients. physicians who were ≥5 years postresidency were more confident in knowing when surgical treatments should be discussed (p=0.004) and managing mild hs (p=0.046), compared to those <5 years postresidency. a large percentage of providers in this study reported a lack of confidence in diagnosing or managing pediatric patients with hs. this may lead to delayed diagnosis and suboptimal treatment. a 2021 study of 481 pediatric hs patients found that the average time to hs diagnosis was almost 2 years, with nearly 80% presenting with hs complications such as scarring and psychological distress at the time of their first dermatology clinic visit.3 timely treatment of hs may enhance methods results discussion skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 683 table 1. survey respondents’ demographic characteristics*. demographic characteristics n (%) gender (n=50) female 39 (78.0%) male 10 (20.0%) prefer not to specify 1 (2.0%) age, mean ± sd (range) (n=50) 39.1 ± 7.9 (27-65) average number of hs patients seen per month, mean ± sd (range) 0.7 ± 0.8 (0-3) type of provider (n=50)† physician (md/do) 47 (94.0%) attending physician (training completed) 39 (83.0%) resident 6 (12.8%) fellow 2 (4.2%) pas/nps 3 (6.0%) number of attending years in practice, mean ± sd (range) (n=39) 9.8 ± 6.2 (1-28) practice setting (n=50) community 32 (64.0%) academic 18 (36.0%) practice location (n=50) urban 26 (52.0%) suburban 23 (46.0%) rural 1 (2.0%) disease severity of the typical hs patient seen (n=25) stage i 16 (64.0%) stage ii-iii 6 (24.0%) equal amounts of hurley i and ii-iii 3 (12.0%) abbreviations: n, number; sd, standard deviation; pa, physician’s assistant; np, nurse practitioner; hs, hidradenitis suppurativa *listservs included the university of california, los angeles pediatrics department, los angeles county-university of southern california pediatrics department, university of north carolina at chapel hill pediatrics department, a private practice pediatric group in north carolina, and a pediatric facebook online group. †all respondents practiced general pediatrics except one was a pediatric gastroenterologist skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 684 figure 1. pediatric providers' self-reported confidence level regarding hs diagnosis and management (n=50). skin march 2023 volume 7 issue 2 (c) 2022 the authors. published by the national society for cutaneous medicine. 685 therapeutic response and prevent irreversible tissue damage.4 increased awareness of the metabolic, endocrine, and psychosocial associations of hs is necessary as pediatric providers play an important role in screening for and addressing these issues.5 special considerations for females include screening for pcos and using ocps/spironolactone to treat post-pubertal adolescents with hormonal hs flares.6 other key pediatric management domains include addressing school-related challenges that hs patients may face and utilizing an evidence-based standard of care approach for first-line management of hs. study limitations include a small number of respondents and a us-based study population. the number of pediatric providers who reported not seeing any hs patients may have been skewed by underdiagnosis of hs. increased educational resources for pediatricians and collaboration with dermatologists may improve hs care for pediatric patients. acknowledgements: we would like to thank the respondents who participated in our study. conflict of interest disclosures: cjs is a speaker for abbvie and novartis, consultant for abbvie, novartis, ucb, alumis, incyte, sonoma biotherapeutics, and inflarx, is an investigator for abbvie, novartis, ucb, inflarx, chemocentryx, and incyte, and is on the board of the hsf. vys is on the board of directors for the hidradenitis suppurativa foundation (hsf), an advisor for the national eczema association, is a stock shareholder of learn health and has served as an advisory board member, investigator, speaker, and/or received research funding from sanofi genzyme, regeneron, abbvie, genetech, eli lilly, novartis, sun pharma, leo pharma, pfizer, incyte, boehringer ingelheim, alumis aristea therapeutics, menlo therapeutics, dermira, burt’s bees, galderma, kiniksa, ucb, target-pharmasolutions, altus lab/cquell, myor, polyfins technology, gpskin and skin actives scientific. jlh is on the board of directors for the hidradenitis suppurativa foundation, has served as a consultant for boehringer ingelheim, novartis, and ucb, and has served as a consultant and speaker for abbvie. all other authors report no conflicts of interest. funding: none corresponding author: jennifer l. hsiao, md associate clinical professor, usc dermatology 1441 eastlake ave, ezralow tower, suite 5301 los angeles, ca 90033 phone: (310) 601-3367 email: j.hsiao.publications@gmail.com references: 1. alikhan a, lynch pj, eisen db. hidradenitis suppurativa: a comprehensive review. journal of the american academy of dermatology. 2009;60(4):539-561. doi:10.1016/j.jaad.2008.11.911 2. hallock kk, mizerak mr, dempsey a, maczuga s, kirby js. differences between children and adults with hidradenitis suppurativa. jama dermatol. 2021;157(9):1095. doi:10.1001/jamadermatol.2021.2865 3. liy-wong c, kim m, kirkorian ay, et al. hidradenitis suppurativa in the pediatric population: an international, multicenter, retrospective, cross-sectional study of 481 pediatric patients. jama dermatol. 2021;157(4):385-391. doi:10.1001/jamadermatol.2020.5435 4. marzano av, genovese g, casazza g, et al. evidence for a ‘window of opportunity’ in hidradenitis suppurativa treated with adalimumab: a retrospective, real‐life multicentre cohort study*. br j dermatol. 2021;184(1):133-140. doi:10.1111/bjd.18983 5. seivright jr, collier e, grogan t, hogeling m, shi vy, hsiao jl. physical and psychosocial comorbidities of pediatric hidradenitis suppurativa: a retrospective analysis. pediatr dermatol. 2021;38(5):1132-1136. doi:10.1111/pde.14765 6. collier ek, price kn, grogan tr, naik hb, shi vy, hsiao jl. characterizing perimenstrual flares of hidradenitis suppurativa. international journal of women’s dermatology. 2020;6(5):372-376. doi:10.1016/j.ijwd.2020.09.002 abigail cline, md, phd, emily l. unrue, bs, leah a. cardwell, md, hossein alinia, md, rechelle tull, bs, steven r. feldman, md, phd, and, william w. huang, md adrian pona1, md, abigail cline1, md, phd, sree s. kolli1, ba, steven r. feldman1,2,3, md, phd. 1 center for dermatology research, department of dermatology, wake forest school of medicine, winston-salem, north carolina 2 department of pathology, wake forest school of medicine, winston-salem, north carolina 3 department of social sciences & health policy, wake forest school of medicine, winston-salem, north carolina demographics, adherence, and satisfaction of home uv phototherapy in psoriasis introduction narrowband uvb phototherapy offers an efficacious and safe treatment option in patients with diffuse psoriasis. however, phototherapy is usually office-based, resulting in frequent travel, costly copayment, and poor treatment adherence. [1] a domestic uvb phototherapy device offers similar efficacy and safety profile to office-based phototherapy. [2,3] we present a novel handheld narrowband uvb phototherapy device to address localized plaque-type psoriasis with a primary intention of gathering insights in demographics, adherence, and patient satisfaction. materials and methods in this retrospective, open-label clinical study, treatment data was collected from 36 patients (14 males and 16 females) with plaque-type psoriasis using a novel home phototherapy system. the battery-operated phototherapy device uses uvb leds and an optical filter to deliver nbuvb predominately in the 300 to 320 nm range. patients administered treatment at home using the scheduling, dosing and guidance built into the system. the phototherapy system was also used to remotely monitor patient treatments, collecting treatment records and adherence data. dosing was based on american academy of dermatology nb-uvb dosing guidelines for psoriasis. treatments were scheduled three times per week until clearance was achieved, at which time treatment frequency and dosing were reduced in accordance with the protocol. adherence was calculated by the number of treatments/opportunities over the first 20 treatments or first 40 opportunities. patient satisfaction was measured using a five-point likert scale. results patient ages ranged from 10-65, with a mean age of 41. there were no differences in adherence or satisfaction between genders or age groups. females had more treatment spots than men (13.1 vs 20.8, respectively (p=0.03)). patients aged 30-39 had more treatment spots (26.6) compared to patients <29 (10.5) and patients 40-49 (13.4) (p=0.005 and p=0.002, respectively). table 1. patient adherence. figure 1. improvement in psoriasis with home phototherapy. top pictures were taken before initiation of phototherapy and bottom pictures were after phototherapy. (a) phototherapy alone before and after 3 weeks, adherence 100%. (b,c,d) phototherapy and biologic treatment before and after 16 weeks, adherence 96%. table 2. treatment spots and patient satisfaction figure 2. in male patients, patient age negatively correlated with adherence (r=-0.683, p=0.007). conclusion the smartphone connected home uvb phototherapy system offers a convenient and satisfactory treatment option for psoriasis patients. references 1. rajpara an1, o'neill jl, nolan bv, yentzer ba, feldman sr. review of home phototherapy. dermatol online j. 2010 dec 15;16(12):2. 2. koek mb, buskens e, van weelden h, steegmans ph, bruijnzeel-koomen ca, sigurdsson v. home versus outpatient ultraviolet b phototherapy for mild to severe psoriasis: pragmatic multicentre randomised controlled non-inferiority trial (pluto study). bmj. 2009 may.338:b1542. [pubmed: 19423623] 3. koek mb, sigurdsson v, van wh, et al. cost effectiveness of home ultraviolet b phototherapy for psoriasis: economic evaluation of a randomised controlled trial (pluto study). bmj 2010;340:c1490 disclosures dr. feldman has received research, speaking and/or consulting support from a variety of companies including galderma, gsk/stiefel, almirall, leo pharma, baxter, boeringer ingelheim, mylan, celgene, pfizer, valeant, taro, abbvie, cosmederm, anacor, astellas, janssen, lilly, clarify, merck, merz, novartis, regeneron, sanofi, novan, parion, qurient, national biological corporation, caremark, advance medical, sun pharma, suncare research, informa, uptodate and national psoriasis foundation. he is founder and majority owner of www.drscore.com and founder and part owner of causa research, a company dedicated to enhancing patients’ adherence to treatment. group mean number of treatment spots median number of treatment spots mean satisfaction median satisfaction sex men 20.8 14.5 3.6 3.0 women 13.1 11.5 3.9 4.0 age under 30 10.5 11.5 4.0 4.0 30-39 26.6 27.5 3.8 4.0 40-49 13.4 11.0 3.6 3.0 50 + 14.0 9.0 3.8 4.0 overall 16.7 12.5 3.75 4.0 group mean rate of adherence (%) median rate of adherence (%) sex men n=14 53.8% 52.0% women n=16 60.0% 59.5% age under 30 n=4 64.7% 69.4% 30-39 n=8 51.4% 44.5% 40-49 n=11 67.5% 74.1% 50+ n=7 43.1% 25.0% overall n=30 57.1% 54.9% b c a b c d skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 599 brief articles primary mucinous carcinoma of the nasal bridge leon kou, bs1, lily zhong, bs1, sid danesh, md2 1medical student, des moines university college of osteopathic medicine, des moines, ia 2board certified dermatologist, danesh dermatology, beverly hills, ca primary cutaneous mucinous carcinoma (pcmc) is an extremely rare appendage tumor with an incidence rate of less than 0.1 cases per million individuals.1 it is often clinically missed due to its unremarkable presentation as a small indolent, asymptomatic nodule that may be indurated or ulcerated. mucinous carcinoma is a malignant tumor with a low rate of metastasis, but high rate of recurrence. it can rarely arise as a primary lesion from the skin or as a metastatic lesion from distant sites, most commonly the breast or gastrointestinal tract.2 it is clinically impossible to differentiate between pcmc or metastatic cutaneous mucinous carcinoma (mcmc) and detailed imaging studies and immunohistochemical investigations are usually required to definitively diagnose pcmc.1 there is no standard of care established for treatment of pcmc and although rare, distant metastasis is highly resistant to both chemotherapy and radiotherapy.3 in this report, we highlight a case of pcmc on the nasal bridge that was refractory to two previous surgical interventions and ultimately treated successfully with mohs surgery. a 62-year-old iranian female presented with complaint of a cystic lesion on her left nasal bridge. the lesion was previously removed by two outside dermatologists but has since recurred. previous pathology reports and medical records were unavailable for review. past medical history if significant for breast cancer treated with chemotherapy and radiotherapy. physical exam showed a welldemarcated nodule on the left nasal bridge (figure 1). excisional biopsy of the lesion was performed. the lesion was described microscopically as neoplasm in the dermis comprised of islands abstract mucinous carcinoma is a rare appendage tumor that is resistant to surgery, chemotherapy, and radiotherapy. it has an unremarkable appearance and must be distinguished as a primary tumor or as a metastasis from distant sites. detailed imaging studies and immunohistochemical investigation are often essential. here, we report a case of surgeryrefractory primary mucinous carcinoma on the left nasal bridge in a 62-year-old female that ultimately required removal by mohs surgery. introduction case presentation skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 600 figure 1. mucinous carcinoma presenting as a welldemarcated nodule on the left nasal bridge. of epithelioid cells with abundant mucin around and inside the islands (figure 2). the preliminary diagnosis was probable primary cutaneous mucinous carcinoma. since the patient was already established with an oncologist and monitored for breast cancer treatment and signs of metastasis, other sources of malignancy were excluded. diagnosis of pcmc was established based on history and histologic findings. due to the lesion’s resistance to surgical excision and extension beyond the deep surgical margin, the patient was referred to a mohs surgeon for removal of the remaining lesion. pcmc is a rare appendage tumor of sweat glands with an estimated 200 cases reported in literature, with less than 150 reported in english.5 the abundance of mucin in pcmc interferes with nutrition of the tumor cells and is thought to be responsible for the slow growing course of the lesions.5 due to its indolent course, pcmc can be easily overlooked, and patients often present to the clinic after noticing its gradual enlargement. affected individuals usually present in their 50-70s, affecting twice as many men than women. meta-analysis by kamalpour et al found that white patients (77.2%) are disproportionally more affected when compared to asian (12.7%) or african (10.1%) patients.6 pcmc commonly arises in the periorbital region followed by nonperiorbital regions of the face and neck, scalp, axilla and genital areas. the lesion size varies from 1.0-8.0 cm, averaging 1.5 cm in diameter.6 pcmc can have wide-ranging appearances. most often, it presents as a wellcircumscribed, slow-growing, painless, firm or soft nodule, but can also present as papillomatous or pedunculated lesions.1,7 they may also be ulcerated, indurated, crusted with telangiectasias or appear as cysts.7 the color of the lesions also varies greatly – ranging from flesh colored to grey, purple, red or blue tinged.1 based on the clinical exam, several lesions such as cysts, basal cell carcinoma, keratoacanthoma, nevus, apocrine hidrocystoma, or even kaposi sarcoma can be on the differential. since this lesion has no characteristic physical or clinical features, histological examination is required for nearly all diagnosis of pcmc. the who has classified these sweat gland tumors as both apocrine and eccrine; however, the prevailing theory leans towards eccrine differentiation based on immunohistochemical and ultrastructural features.9 histologically, pcmc is described as nests of neoplastic epithelial cells floating discussion skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 601 figure 2. (a) neoplasm in the dermis comprised of islands of epithelioid cells with abundant mucin around and inside the islands (h&e, 40x). (b) individual clusters of epithelial cells surrounded by mucin (h&e, 400x). in mucinous lakes.9 it is nearly impossible to histologically differentiate pcmc from mcmc; thus, immunohistochemical and imaging studies, such as pet-ct, x-ray, ct and ultrasound are vital for determining whether the lesion is primary or secondary.3 mcmc most commonly originates from the breast, gastrointestinal tract, salivary glands, lacrimal glands, nose, paranasal sinuses, bronchi, renal pelvis and ovaries. mcmc from the breast and gastrointestinal tract can mimic clinical appearance of pcmc; thus, it is of special importance to distinguish pcmc from mcm from these sites.10 absence of expression for cytokeratin (ck) 20 can be used to exclude diagnosis of metastatic colorectal mucinous carcinoma.11 one study of 5 pcmc samples found that positive staining for ck7, p63, and ck5/6 was indicative of pcmc, with ck7 being most indicative.11 in our patient, immunohistochemical staining was not used, but given a history of recurrent mucinous carcinoma and no other source of metastasis, pcmc is the most likely diagnosis. pcmc generally has a good prognosis. most forms of metastasis are through direct invasion of local regions; however, direct invasion into lymphatics, skeletal muscle, bone, dura, and periosteum is also possible.12 there are currently no guidelines for treatment of pcmc. one meta-analysis found that in 159 cases of pcmc with follow up, the cases treated with mohs surgery with a mean follow up time of 23.1 months had a 13% recurrence rate and no cases of metastasis.6 the study also found that pcmc treated with excision with a mean follow up time of 30.1 months showed that 34% recurred or metastasized. our patient’s pcmc required a total of four surgical interventions for resolution. this can be financially costly and have a negative effect on patient’s self-image and cosmetic appearance. therefore, we believe that mohs surgery is the preferred treatment after initial diagnosis of pcmc. radiation and chemotherapy are not advised for treatment as pcmc have been reported to be resistant to both modalities.4 pcmc is a rare, malignant appendage tumor with an unremarkable clinical appearance. early recognition, proper workconclusion a. b. skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 602 up and treatment of this highly recurrent, chemotherapy and radiotherapy-resistant lesion is essential to avoid potential metastasis. we hope that this case report contributes to the future development of diagnosis and treatment guidelines for pcmc. conflict of interest disclosures: none funding: none corresponding author: sid danesh, md 240 s. la cienega blvd beverly hills, ca 90211 phone: -310-550-0666 email: siddanesh@gmail.com references: 1. albasri am, ansari ia, aljohani ar, alhujaily as. primary mucinous adenocarcinoma of the eyelid. saudi med j. 2018;39(9):940-945. doi:10.15537/smj.2018.9.22512 2. carson hj, gattuso p, raslan wf, reddy v. mucinous carcinoma of the eyelid. an immunohistochemical study. am j dermatopathol. 1995;17(5):494-498. doi:10.1097/00000372-199510000-00011 3. miyachi h, hashimoto h, suehiro k, et al. aromatase inhibitor for the treatment of primary mucinous carcinoma of the skin with distant metastasis. jaad case rep. 2018;4(3):235-238. doi:10.1016/j.jdcr.2017.10.021 4. papalas ja, proia ad. primary mucinous carcinoma of the eyelid: a clinicopathologic and immunohistochemical study of 4 cases and an update on recurrence rates. arch ophthalmol. 2010;128(9):1160-1165. doi:10.1001/archophthalmol.2010.177 5. sanft d-m, zoroquiain p, arthurs b, burnier mn. primary mucinous adenocarcinoma of the eyelid: a case-series. hum pathol case rep. 2017;9:1923. doi:10.1016/j.ehpc.2016.12.006 6. kamalpour l, brindise rt, nodzenski m, bach dq, veledar e, alam m. primary cutaneous mucinous carcinoma: a systematic review and meta-analysis of outcomes after surgery. jama dermatol. 2014;150(4):380-384. doi:10.1001/jamadermatol.2013.6006 7. kelly bc, koay j, driscoll ms, raimer ss, colome-grimmer mi. report of a case: primary mucinous carcinoma of the skin. dermatol online j. 2008;14(6):4. 8. coan eb, doan a, allen c. mucinous eccrine carcinoma: a rare case of recurrence with lacrimal gland extension. ophthal plast reconstr surg. 2012;28(5):e109-110. doi:10.1097/iop.0b013e31823c80ba 9. beteddini osa, sheikh s, shareefi f, shahab r. primary mucinous adenocarcinoma of the scalp: a case report and literature review. int j surg case rep. 2015;10:241-244. doi:10.1016/j.ijscr.2015.02.006 10. mardi k, diwana vk. primary cutaneous mucinous carcinoma: a rare entity. indian dermatol online j. 2011;2(2):82-84. doi:10.4103/2229-5178.85997 11. levy g, finkelstein a, mcniff jm. immunohistochemical techniques to compare primary vs. metastatic mucinous carcinoma of the skin. j cutan pathol. 2010;37(4):411-415. doi:10.1111/j.1600-0560.2009.01436.x 12. warycha m, kamino h, mobini n, hale ek. primary mucinous carcinoma with direct histopathologic evidence of lymphatic invasion. j drugs dermatol jdd. 2006;5(7):655-658. mailto:siddanesh@gmail.com acknowledgements: medical writing support was provided by prescott medical communications group (chicago, il) with financial support from ortho dermatologics | presented at the fall clinical dermatology conference • october 17-20, 2019 • las vegas, nv synopsis ◾ psoriasis is a chronic, immune‑mediated disease that can have frequent exacerbations and remissions1,2 ◾ topical corticosteroids are the mainstay of psoriasis treatment3; however, safety concerns limit their use4 ◾ combination therapy may optimize efficacy while minimizing safety and tolerability concerns ◾ few studies have examined the efficacy and safety of topical therapies for the treatment of psoriasis in hispanic patients objective ◾ to investigate the efficacy, safety, and tolerability following once‑daily application of a fixed combination lotion containing halobetasol propionate 0.01% and tazarotene 0.045% (hp/taz; duobrii™ ortho dermatologics, bridgewater, nj) in hispanic patients with moderate‑to‑severe plaque psoriasis methods ◾ in two phase 3, multicenter, double‑blind, vehicle‑controlled studies (nct02462070 and nct02462122), participants were randomized (2:1) to receive hp/taz or vehicle once‑daily for 8 weeks, with a 4‑week posttreatment follow‑up5 • in these studies, cerave® hydrating cleanser and cerave® moisturizing lotion (l’oreal, ny) were provided as needed for optimal moisturization/cleaning of the skin ◾ data from these two studies were pooled and analyzed post hoc in a subset of self‑identified hispanic participants ◾ efficacy assessments included treatment success (≥2‑grade improvement from baseline in the investigator global assessment [iga] score and a score of ‘clear’ or ‘almost clear’ [primary endpoint]), impact on individual signs of psoriasis (erythema, plaque elevation, and scaling) at the target lesion, body surface area (bsa), and reduction from baseline in mean igaxbsa ◾ safety and treatment‑emergent adverse events (teaes) were evaluated throughout the study results ◾ a total of 115 hispanic participants were included in this analysis ◾ by week 8, 39.3% of participants achieved treatment success with hp/taz compared with 9.3% on vehicle (p=0.002); this effect was sustained posttreatment (figure 1) ◾ hp/taz lotion was also significantly superior in reducing psoriasis signs; at week 8, significantly more hp/taz‑treated participants achieved ≥2‑grade improvement in erythema (46.8%), plaque elevation (58.1%), and scaling (63.2%) compared with vehicle (12.7%, 11.2%, and 22.2%, respectively; p<0.001 all) andrew f alexis, md, mph1; paul s yamauchi, md, phd2; tina lin, pharmd3; gina martin, mot4 1department of dermatology, mount sinai st luke’s and mount sinai west, new york, ny; 2dermatology institute & skin care center, inc., santa monica, ca; 3ortho dermatologics, bridgewater, nj; 4bausch health americas, petaluma, ca figure 2. mean percent change from baseline in igaxbsa by study visit (itt population; pooled data) hp/taz (n=78) vehicle (n=37) -60% -30% -40% -50% -20% -10% 10% 0% 20% study visit (weeks) m e a n p e rc e n t c h a n g e f ro m b a se lin e 0 2 4 6 8 12 treatment posttreatment *p=0.016 vs vehicle; **p<0.001 vs vehicle. bsa, body surface area; hp/taz, halobetasol propionate 0.01% and tazarotene 0.045%; iga, investigator global assessment; itt, intent‑to‑treat. ◾ the most frequently reported treatment‑related teaes were contact dermatitis (3.9%) and skin atrophy (3.9%; table 1) • four participants (5.3%) treated with hp/taz lotion discontinued due to teaes table 1. summary of treatment-emergent adverse events through week 8 (safety population; pooled data) n (%) hp/taz lotion (n=76) vehicle lotion (n=36) participants reporting any teaes 26 (34.2) 8 (22.2) participants reporting any saes 1 (1.3) 0 deaths 0 0 participants discontinuing due to teaes 4 (5.3) 2 (5.6) severity of teaes mild 11 (14.5) 4 (11.1) moderate 12 (15.8) 3 (8.3) severe 3 (3.9) 1 (2.8) relationship to study drug related 14 (18.4) 3 (8.3) unrelated 12 (15.8) 5 (13.9) treatment‑related teaes reported in ≥2% of participants contact dermatitis 3 (3.9) 0 skin atrophy 3 (3.9) 0 burning sensation 2 (2.6) 1 (2.8) pruritis 1 (1.3) 1 (2.8) psoriasis 0 1 (2.8) hp/taz, halobetasol propionate 0.01% and tazarotene 0.045%; sae, serious adverse event; teae, treatment‑emergent adverse event. conclusions ◾ hp/taz lotion was associated with significant, rapid, and sustained reductions in disease severity in a hispanic population with moderate‑to‑severe psoriasis, with good tolerability and safety over 8 weeks of once‑daily use references 1. nestle fo, et al. n engl j med. 2009;361(5):496‑509. 2. cohen sn, et al. clin exp dermatol. 2012;37 suppl 1:13‑18. 3. menter a, et al. j am acad dermatol. 2009;60(4):643‑659. 4. lam lh, et al. j drugs dermatol. 2016; 15(8):945‑948. 5. sugarman jl, et al. j drugs dermatol. 2018;17(8):855‑861. author disclosures af alexis has received grants/research support from almirall, bristol‑myers‑squibb, celgene, galderma, leo, menlo, novartis, skinmedica, and bausch health; and has served as a consultant for beiersdorf, bristol‑myers‑squibb, celgene, dermavant, galderma, leo, l’oreal, menlo, novartis, pfizer, sanofi‑regeneron, scientis, ucb, unilever, and bausch health. ps yamauchi has served as speaker, consultant, and investigator for abbvie, amgen, janssen, novartis, lilly, leo, ortho dermatologics, and sun pharma. t lin is an employee of ortho dermatologics. g martin is an employee of bausch health americas inc. ◾ participants treated with hp/taz lotion achieved a 40.7% mean reduction from baseline in bsa at week 8 versus a 10.1% increase with vehicle (p=0.002), and a 50.5% mean reduction in igaxbsa score versus an 8.5% increase with vehicle (p<0.001); effects were sustained posttreatment (figure 2) ◾ hp/taz lotion demonstrated rapid reduction in disease severity, with significant improvements versus placebo observed by week 2 for igaxbsa reduction and by week 4 for treatment success figure 1. percentage of participants achieving treatment successa by study visit (itt population; pooled data) 0% 30% 20% 10% 40% 50% 60% 70% 80% 90% 100% study visit (weeks) p e rc e n ta g e o f p a rt ic ip a n ts 0 2 4 6 8 12 treatment posttreatment hp/taz (n=78) vehicle (n=37) * p=0.034 vs vehicle; **p=0.003 vs vehicle; ***p=0.002 vs vehicle; ****p<0.001 vs vehicle. atreatment success was defined as ≥2‑grade improvement from baseline in iga score and a score of ‘clear’ or ‘almost clear’. hp/taz, halobetasol propionate 0.01% and tazarotene 0.045%; iga, investigator global assessment; itt, intent‑to‑treat. efficacy, safety, and tolerability of a halobetasol 0.01%/tazarotene 0.045% fixed combination in the treatment of moderate‑to‑severe plaque psoriasis in a hispanic population: post hoc analysis of two phase 3 randomized controlled trials powerpoint presentation • this investigation finds no difference in local skin reactions in treatment areas >20 cm2 after incubation with 10% ala gel followed by 10 j/cm2 blue light compared to 37 j/cm2 red light illumination. • pdt with 10% ala gel in regions larger than 20cm2 illuminated by either red light or blue light report fewer local skin reactions compared to the phase iii clinical trials. • we hypothesize that shorter incubation or full-face pdt treatment may produce less ppix, less ppix-induced cell necrosis, increased ppixinduced cell apoptosis, and decreased irritation.5 • no irritation was observed in winter months of december-february, and in late spring months of may and june; further studies are needed to determine the significance. • efficacy was not examined in this study, so it is unknown whether decreased irritation suggests decreased efficacy. • irritation may be mitigated by stringent adherence to a specific pdt post-care regimen using sunblock and healing creams every 2 hours during waking hours for 48 hours after pdt treatment. safety of large field (>20cm2) photodynamic therapy using 10% aminolevulinic acid hydrochloride nanoemulsion gel comparing blue to red light illumination • actinic keratoses (aks) are precursor lesions that may progress to squamous cell carcinomas.1,2 • treatment of aks has traditionally involved cryotherapy, 5-fluorouracil, and other topical therapies. with a growing desire for u.s. dermatologists to treat field cancerization and to increase patient compliance, photodynamic therapy (pdt) has become an important treatment modality.3 • photodynamic therapy with 10% aminolevulinic acid hydrochloride nanoemulsion gel (10% ala gel; biofrontera) followed by red light illumination was approved in the u.s. for the treatment of aks and healthy surrounding skin up to 20 cm2 in may, 2016. • photodynamic therapy with 10% ala gel has been shown to have fewer local skin reactions compared to the use of 20% ala solution on treatment areas 25 cm2.4 • in the clinical setting, u.s. dermatologists routinely use pdt to treat cancerous fields >25cm2 with blue or red light. however, it is unclear in regions >25cm2 if the light source used correlates to observed local skin reactions. • this study compares local skin reactions after 10 j/cm2 blue light or 37 j/cm2 red light illumination following pdt with 10% ala gel on treatment areas >20 cm2. introduction results 1. dodds, a., a. chia, and s. shumack, “actinic keratosis: rationale and management.” dermatol ther (heidelb), 2014. 4(1): 11-31. 2. reinhold u, dirschka t, ostendorf r, aschoff r, berking c, philipp-dormston wg, hahn s, lau k, jäger a, schmitz b, lübbert h, szeimies rm. “a randomized, double-blind, phase iii, multicentre study to evaluate the safety and efficacy of bf-200 ala (ameluz(®) ) vs. placebo in the field-directed treatment of mild-to-moderate actinic keratosis with photodynamic therapy (pdt) when using the bfrhodoled(®) lamp.” br j dermatol, 2016:175(4):696-705. 3. reinhold u. “a review of bf-200 ala for the photodynamic treatment of mild-tomoderate actinic keratosis.” future oncol, 2017:13(27):2413-2428 4. nestor et al. “safety and efficacy of aminolevulinic acid 10% topical gel versus aminolevulinic acid 20% topical solution followed by blue-light photodynamic therapy for the treatment of actinic keratosis on the face and scalp: a randomized, double-blind study.” j clin aesthet dermatol. 2019;12:32-38. 5. warren cb, lohser s, wene lc, pogue bw, bailin pl, maytin ev. noninvasive fluorescence monitoring of protoporphyrin ix production and clinical outcomes in actinic keratoses following shortcontact application of 5-aminolevulinate. j biomed opt. 2010;15(5):051607. *biofrontera provided partial funding for chart review and analysis in this investigator initiated trial. angela yen moore, md 1, 2, 3,4; stephen moore1 1arlington research center, arlington, tx; 2baylor university medical center, dallas, tx; 3university of texas medical branch at galveston, tx; 4texas college of osteopathic medicine, unt health science center, fort worth, tx • this is a retrospective, descriptive case series in texas from january 1december 31, 2018 that compared the safety data on 190 patients with ak treatment areas >20cm2 with blue light compared to red light illumination. • after debridement, one tube (2 grams) of 10% ala gel was utilized in each treatment area >20cm2 for all 279 pdt treatments and incubated on full face and ears (face) for 60 minutes prior to illumination but incubated for 90 minutes with plastic wrap occlusion on the bilateral dorsal hands (hands), bilateral dorsal wrists to elbows (arms), scalps (scalp), decolletés (chest), anterior or posterior necks (neck), bilateral shins or calves (legs), and upper backs (back) prior to illumination. • incubation was followed by illumination by either narrowband blue light [dusa, 417nm] or narrowband red light [galderma, 630nm]. • a specific pdt post-care regimen was recommended to expedite healing and decrease irritation by applying physical sunblock zinc oxide 10% (sunblock) and topical restorative skin cream with zinc and copper [avene] and/or post-procedure laser gel [elta] (healing creams) simultaneously every 2 hours during waking hours for 48-96 hours after pdt treatment. • data is reported by treatment area for irritation (stinging/burning, dryness, scaling, and erythema), post-pdt care, extent of irritation (level 5-strong burning and scaling; level 4-persistent mild burning, scaling, redness; level 3-persistent redness with minimal scaling; level 2temporary redness and scaling; level 1-mild temporary redness without scaling) and month of irritation. irritation was reported from 1-28 days post pdt. methods • irritation after sessions was observed (from greatest to least) in 8.4% (11/131) full face and ears (face), 6.3% (1/16) bilateral dorsal hands and fingers (hands), 3.2% (1/31) scalps (scalp), 0% (0/10) bilateral dorsal wrists to elbows (arms), 0% (0/8) decolletés (chest), 0% (0/2) anterior/posterior necks (neck), 0% (0/5) on bilateral shins or calves (legs), and 0% (0/1) upper back (back) (table 1). • greatest incidence of the 4.7% (13/279) of patients with irritation after pdt occurred on the face in 84.6% (11/13), followed by hands in 7.7% (1/13) scalp in 7.7% (1/13), and none on arms, neck, legs, chest, and back (table 1). • no statistical difference in irritation with pdt treatments existed between red light and blue light illumination (p=0.68) (figure 1). • after pdt with blue light illumination, 5% (4/76) of patients experienced irritation in 4% (4/103) of pdt treatments (figure 1). • after pdt with red light illumination, 8% (9/114) of patients experienced irritation in 5% (9/176) of pdt treatments (figure 1). • of the 190 patients, 64.7% (123/190) were males and 35.3% (67/190) were females. ages ranged from 40-95, with a mean age of 74 (table 1). • fitzpatrick skin types included 45.3% (86/190) type 2, 54.2% (103/190) type 3, and 0.5% (1/190) type 4 (table 1). • of the 103 sessions with blue light, pdt treatments included 72.8% (75/103) on face, 2.9% (3/103) on hands, 2.9% (3/103) on arms, 12.6% (13/103) on scalp, 4.9% (5/103) on chest, 1.9% (2/103) on neck, 1.0% (1/103) on legs, and 1.0% (1/103) on back (table 1). • overall irritation incidence in was 4.7% (13/279). of the 176 sessions with red light, pdt treatments included 74.4% (131/176) on full face and ears (face), 7.4% (13/176) on bilateral dorsal hands (hands), 4.0% (7/176) on bilateral dorsal wrists to elbows (arms), 10.2% (18/176) on scalps (scalp), 1.7% (3/176) on decolletés (chest), 0.0% (0/176) on anterior or posterior necks (neck), 2.3% (4/176) on bilateral shins or calves (legs), and 0.0% (0/176) on upper backs (back) (table 1). results • irritation after pdt with blue light illumination was graded level 5 (strong burning and scaling) in 1 session, level 4 (persistent mild burning, scaling, redness) in 2 sessions, and level 3 (persistent redness with minimal scaling) in 1 session (figure 2). • irritation after pdt with red light illumination was graded level 5 (strong burning and scaling) in 2 sessions, level 3 (persistent redness with minimal scaling) in 2 sessions, level 2 (temporary redness and scaling) in 3 sessions, and level 1 (temporary redness without scaling) in 2 sessions (figure 2). • 1 of the 15 sessions in april, 2 out of the 18 sessions in july, 1 out of the 9 sessions in august, 2 out of the 25 sessions in september, 5 out of the 53 sessions in october, and 2 out of the 45 sessions in november had irritation after pdt. none of the other months had any irritation after pdt (figure 3). • of the 95.3% (266/279) pdt sessions without irritation, subjects were compliant with a specific pdt post-care regimen to apply physical sunblock zinc oxide 10% [elta] (sunblock) and topical restorative skin cream with zinc and copper [avene] and/or post-procedure laser gel [elta] (healing creams) simultaneously every 2 hours during waking hours for 48-96 hours after pdt treatment. conclusions references average 74 74 73 74 74 76 age range 40-95 n/a 40-83 46-92 n/a 68-81 sessions (n=176) patients (n=114) sessions with irritation (n=9) sessions (n=103) patients (n=76) sessions with irritation (n=4) male 114 74 5 69 49 4 female 62 40 4 34 27 0 arms 7 n/a 1 3 n/a 0 hands 13 n/a 1 3 n/a 0 face 131 n/a 7 75 n/a 4 legs 4 n/a 0 1 n/a 0 neck 0 n/a 0 2 n/a 0 chest 3 n/a 0 5 n/a 0 scalp 18 n/a 0 13 n/a 0 back 0 n/a 0 1 n/a 0 fitzpatrick skin type 1 0 0 0 0 0 0 2 70 46 3 53 40 2 3 105 67 6 50 36 2 4 1 1 0 0 0 0 5 0 0 0 0 0 0 red light blue light age sex location table 1: patient demographics microsoft word july 2020 comp 721 proof returned.docx skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 391 compelling comments to our brown skin girls padmavathi v. karri, bsw1, datonye o. charles, md1, brina v. bui, md1 1uthealth mcgovern medical school, houston, tx melanocytes are a type of skin cell in the epidermis that produce melanin, which is what gives skin its color. the more melanin someone has the darker their skin. far too often darker skin is thought to be unattractive or of lesser value.1 the alarming number of skin lighteners and bleaching treatments in asian and african cultures are proof of skin color hierarchy.1,2 in 2017, the global skinlightening industry was worth several billions with as much as 61% of women in india use skin-lightening cream and 77% in nigeria.1–3 instead of pointing fingers at those choosing to lighten their complexion, we must instead bring awareness and change to the society that discriminates against darker skin. in recent years multiple social media movements have made strides to dismantle the notion brown is not beautiful. popular instagram hashtags to celebrate dark skin are “melaninpoppin”, “melaninqueen”, and “blackgirlmagic” with over 20 million tags. most recently, beyoncé’s song “brown skin girl” celebrates the enormous beauty inherent in brown and black skin that is often maligned and overlooked—this message is one that can be amplified by physicians. dermatologists have a unique and relevant role in supporting patients in their journey to love the shade of their skin. an essential part of that is preventing and stopping unsafe skin lightening and bleaching practices. these colorism-promoting products are a public health concern as they propagate an unhealthy obsession to chase fairer skin using dangerous, unregulated ingredients.1,3 our population is more diverse than ever, and the messaging and language dermatologists employ in their practice can empower and influence patients’ perceptions of what it means to have beautiful, healthy skin. conflict of interest disclosures: none funding: none corresponding author: padmavathi v. karri uthealth mcgovern medical school 6431 fannin street houston, tx 77030 phone: 469-939-8673 email: padmavathi.v.karri@uth.tmc.edu references 1. shroff h, diedrichs pc, craddock n. skin color, cultural capital, and beauty products: an investigation of the use of skin fairness products in mumbai, india. front public heal. 2018. doi:10.3389/fpubh.2017.00365 2. sagoe d, pallesen s, dlova nc, lartey m, ezzedine k, dadzie o. the global prevalence and correlates of skin bleaching: a meta-analysis and meta-regression analysis. int j dermatol. 2019. doi:10.1111/ijd.14052 3. akiibinu mo, bob soile o, akinade le, akiibinu so. levels of toxic metals in skin lightening agents commonly used in lagos, nigeria. j adv chem. 2019. doi:10.24297/jac.v16i0.8317 deucravacitinib in moderate to severe plaque psoriasis: liver transaminase results from the phase 3 poetyk pso program mark lebwohl,1 alexander egeberg,2 misti linaberry,3 kim hoyt,3 subhashis banerjee,3 renata m kisa,3 bruce strober4 1icahn school of medicine at mount sinai, new york, ny, usa; 2bispebjerg hospital, copenhagen, denmark; 3bristol myers squibb, princeton, nj, usa; 4yale university school of medicine, new haven, and central connecticut dermatology research, cromwell, ct, usa presented at the winter clinical dermatology conference hawaii®, january 13-18, 2023, kohala coast, hi, and winter clinical miamitm, february 17-20, 2023, miami, fl this is an encore of the 2022 fall clinical dermatology conference poster email: lebwohl@aol.com copies of this poster are for personal use only and may not be reproduced without written permission from the authors. synopsis • tyrosine kinase 2 (tyk2) is essential to intracellular signaling of cytokines (interleukin-23 and type i interferons) involved in psoriasis pathogenesis1 (figure 1) • deucravacitinib, an oral, selective, allosteric tyk2 inhibitor, is approved in the us and other countries for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy2 figure 1. mechanism of action of deucravacitinib ty k2 deucravacitinib (allosteric inhibitor class) unique tyk2 regulatory domain catalytic domain (highly conserved across jak family) atp-binding active site (approved jak inhibitor class) •  ≥100-fold greater selectivity for tyk2 vs jak 1/3 • ≥2000-fold greater selectivity for tyk2 vs jak 2 selectivity in cells1,3: atp, adenosine 5′-triphosphate; jak, janus kinase; tyk2, tyrosine kinase 2. • in two phase 3 pivotal trials in patients with moderate to severe plaque psoriasis, deucravacitinib demonstrated a robust safety and efficacy profile, including superiority to placebo and apremilast4,5 • deucravacitinib treatment did not result in clinically relevant mean changes over time across multiple laboratory parameters, including in measures of liver transaminases6 — mean alanine aminotransferase (alt) and aspartate aminotransferase (ast) levels remained unchanged and within normal limits over weeks 0-166 — increases in liver transaminases have been observed with janus kinase 1/2/3 inhibitors in patients with autoimmune diseases, including plaque psoriasis7 • however, increases ≥3× the upper limit of normal (uln) in alt and ast were observed over 16 weeks in individual patients2 — alt elevations ≥3× uln were reported in 9 patients (3.6/100 person-years [py]) treated with deucravacitinib and in 2 patients (1.6/100 py) receiving placebo who did not have alt elevation at baseline — ast elevations ≥3× uln were reported in 13 patients (5.2/100 py) treated with deucravacitinib and in 2 patients (1.6/100 py) receiving placebo objective • to assess laboratory measures of liver function in the poetyk pso-1 and pso-2 trials, including changes over 52 weeks in patients who experienced an elevation ≥3× uln for alt or ast in the first 16 weeks of treatment methods study designs • poetyk pso-1 and pso-2 were 52-week, multinational, phase 3, double-blind, randomized, placeboand active comparatorcontrolled trials (figure 2) • patients with moderate to severe plaque psoriasis (psoriasis area and severity index [pasi] ≥12, static physician’s global assessment [spga] ≥3, body surface area involvement ≥10%) were randomized 1:2:1 to oral placebo, deucravacitinib 6 mg once daily, or apremilast 30 mg twice daily during weeks 0–16 — patients receiving placebo crossed over to deucravacitinib at week 16 figure 2. poetyk pso-1 and pso-2 study designs deucravacitinib 6 mg qdplacebo (n = 166) deucravacitinib 6 mg qd<pasi 50 apremilast 30 mg bid≥pasi 50 titrate* 1 :2 :1 r an d om iz at io n weeks 16 24 520 deucravacitinib 6 mg qd (n = 332) coprimary endpoints pasi 75 spga 0/1 apremilast 30 mg bida (n = 168) deucravacitinib 6 mg qdplacebo (n = 255) deucravacitinib 6 mg qd (n = 511) deucravacitinib 6 mg qd deucravacitinib 6 mg qd deucravacitinib 6 mg qd deucravacitinib 6 mg qd placebob apremilast 30 mg bida (n = 254) 1 :2 :1 r an d om iz at io n weeks 16 24 520 1:1 deucravacitinib 6 mg qdplacebob <pasi 75 ≥pasi 75 ≥pasi 75 ≥pasi 75 coprimary endpoints pasi 75 spga 0/1 from armstrong aw, et al. deucravacitinib versus placebo and apremilast in moderate to severe plaque psoriasis: efficacy and safety results from the 52-week, randomized, double-blinded, placebo-controlled phase 3 poetyk pso-1 trial. j am acad dermatol. 2023;88:29-39.this work is licensed under a creative commons attribution license (cc by-nc-nd 4.0). https://creativecommons.org/licenses/by-nc-nd/4.0/. from strober b, et al. deucravacitinib versus placebo and apremilast in moderate to severe plaque psoriasis: efficacy and safety results from the 52-week, randomized, double-blinded, phase 3 poetyk pso-2 trial. j am acad dermatol. 2023;88:40-51. this work is licensed under a creative commons attribution license (cc by-nc-nd 4.0). https://creativecommons.org/licenses/by-nc-nd/4.0/. poetyk pso-1 (n = 666) poetyk pso-2 (n = 1020) aapremilast was titrated from 10 mg qd to 30 mg bid over the first 5 days of dosing. bupon relapse (≥50% loss of week 24 pasi percentage improvement from baseline), patients were to be switched to deucravacitinib 6 mg qd. bid, twice daily; pasi, psoriasis area and severity index; pasi 50, ≥50% reduction from baseline in pasi; pasi 75, ≥75% reduction from baseline in pasi; qd, once daily; spga 0/1, static physician’s global assessment of 0 (clear) or 1 (almost clear) with a ≥2-point improvement from baseline. post hoc analysis of changes in liver function • poetyk pso-1 and pso-2 data were pooled by treatment group • alt and ast elevations are presented as: — events classified as adverse events (aes) and aes leading to treatment discontinuation — shifts from baseline to maximum grade (based on the common terminology criteria for adverse events [ctcae] version 5) over weeks 0–16 — maximum elevations over weeks 0–16 and weeks 0–52 — patient-level data for patients who experienced an elevation ≥3× uln during weeks 0–16 results patient population • this analysis included 666 and 1020 patients randomized in poetyk pso-1 and pso-2, respectively aes related to liver abnormalities • the frequencies and exposure-adjusted incidence rates for "alt elevation" and "ast elevation" reported as aes were higher in placebo patients vs patients treated with deucravacitinib or apremilast (table 1) • there was also 1 event of “hepatic function abnormal” (including alt and ast elevations ≥3× uln) in a deucravacitinib-treated patient and 1 event of “liver function test abnormal” (including alt elevation ≥3× uln) in a placebo patient • one patient in each treatment group discontinued in the first 16 weeks because of an altor ast-related ae, including the events of “hepatic function abnormal” and “liver function test abnormal” • there were no cases of drug-induced liver injury table 1. liver abnormalities reported as aes, weeks 0–16 and weeks 0–52 preferred term poetyk pso-1 + pso-2, weeks 0–16 poetyk pso-1 + pso-2, weeks 0–52 placebo (n = 419) deucravacitinib (n = 842) apremilast (n = 422) placebo (n = 666) deucravacitinib (n = 1364) apremilast (n = 422) n (%) n (%) n (%) n (%) total py ir/ 100 py n (%) total py ir/ 100 py n (%) total py ir/ 100 py alt increased 3 (0.7) 2 (0.2) 0 7 (1.1) 247.8 2.8 10 (0.7) 982.0 1.0 2 (0.5) 225.9 0.9 ast increased 2 (0.5) 3 (0.4) 1 (0.2)a 3 (0.5) 249.2 1.2 7 (0.5) 982.3 0.7 1 (0.2)a 226.4 0.4 hepatic function abnormal 0 1 (0.1)b 0 0 0 ― 1 (0.1)b 986.6 0.1 0 0 ― liver function test abnormal 1 (0.2)c 0 0 1 (0.2)c 249.9 0.4 0 ― ― 0 ― ― shading indicates events that led to treatment discontinuation. apatient with no reported medical history and baseline alt 58 u/l (>1× uln) and ast 33 u/l discontinued treatment on day 18 due to increased cpk and increased ast. values at the time of discontinuation were cpk 11,878 u/l (grade 4: reference range, 39-308 u/l), alt 117 u/l (>2× uln), and ast 226 u/l (>5× uln). all values returned to within baseline range on day 53. bpatient with a relevant history of fatty liver and baseline alt 110 u/l (>2× uln), ast 80 u/l (>2× uln), and bilirubin 0.9 mg/dl discontinued treatment on day 59 due to “hepatic function abnormal.” bilirubin levels ranged from 0.9-2.0 mg/dl (reference range, 0-1.2 mg/dl) prior to the reported ae. values on day 58 were: alt 119 u/l (>2× uln), ast 119 u/l (>3× uln), and bilirubin 4.2 mg/dl (>3× uln). the event resolved on day 92. cpatient with a relevant history of fatty liver, increased liver function test, and screening alt 73 u/l (>1× uln) and ast 44 u/l (>1× uln) discontinued treatment on day 2 due to “liver function test abnormal.” values on day 1 were: alt 387 u/l (>5× uln) and ast 177 u/l (>3× uln). values returned to within screening range on day 36. ae, adverse event; alt, alanine aminotransferase; ast, aspartate aminotransferase; cpk, creatine phosphokinase; ir, incidence rate; py, person-years; uln, upper limit of normal. shifts in ctcae grade • definitions of ctcae grades for increased alt and increased ast are defined in table 2 • across treatment arms, maximum increases from baseline in alt and ast rarely exceeded 1 ctcae grade during weeks 0-16 (table 3) — shifts of 1 grade from baseline: • alt: placebo, 11.4%; deucravacitinib, 11.3%; apremilast, 14.6% • ast: placebo, 9.4%; deucravacitinib, 8.6%; apremilast, 6.7% — shifts of ≥2 grades from baseline: • alt: placebo, 0%; deucravacitinib, 0.4%; apremilast, 0.5% • ast: placebo, 0%; deucravacitinib, 0.5%; apremilast, 0.5% table 2. definitions of ctcae grades for alt and ast elevations laboratory parameter grade 1 grade 2 grade 3 grade 4 alt • uln–3× uln if baseline normal • 1.5×–3× baseline if baseline abnormal • >3×-5× uln if baseline normal • >3×-5× baseline if baseline abnormal • >5×–20× uln if baseline normal • >5×–20× baseline if baseline abnormal • >20× uln if baseline normal • >20× baseline if baseline abnormal ast • uln–3× uln if baseline normal • 1.5×–3× baseline if baseline abnormal • >3×-5× uln if baseline normal • >3×-5× baseline if baseline abnormal • >5×–20× uln if baseline normal • >5×-20× baseline if baseline abnormal • >20× uln if baseline normal • >20× baseline if baseline abnormal alt, alanine aminotransferase; ast, aspartate aminotransferase; ctcae, common terminology criteria for adverse events; uln, upper limit of normal. table 3. shifts in transaminase elevations from baseline during weeks 0-16 by ctcae grade ctcae term, n (%) bl grade poetyk pso-1 and pso-2 placebo deucravacitinib 6 mg qd apremilast 30 mg bid maximum grade (weeks 0-16) maximum grade (weeks 0-16) maximum grade (weeks 0-16) 0 1 2 3 4 0 1 2 3 4 0 1 2 3 4 alt increased n = 413 n = 833 n = 419 0 297 (86.3) 47 (13.7) 0 0 0 579 (85.0) 92 (13.6) 3 (0.4) 0 0 287 (82.0) 61 (17.4) 2 (0.6) 0 0 1 55 (87.3) 8 (12.7) 0 0 0 143 (89.9) 14 (8.8) 2 (1.3) 0 0 64 (94.1) 4 (5.9) 0 0 0 2 3 (75.0) 1 (25.0) 0 0 0 0 0 0 0 0 1 (100) 0 0 0 0 3 2 (100) 0 0 0 0 0 0 0 0 0 0 0 0 0 0 4 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 ast increased n = 413 n = 833 n = 419 0 342 (90.0) 38 (10.0) 0 0 0 687 (90.4) 69 (9.1) 3 (0.4) 1 (0.1) 0 344 (92.0) 28 (7.5) 1 (0.3) 1 (0.3) 0 1 27 (90.0) 2 (6.7) 1 (3.3) 0 0 60 (82.2) 10 (13.7) 3 (4.1) 0 0 44 (97.8) 1 (2.2) 0 0 0 2 2 (100) 0 0 0 0 0 0 0 0 0 0 0 0 0 0 3 1 (100) 0 0 0 0 0 0 0 0 0 0 0 0 0 0 4 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 light pink shading indicates shifts of 1 grade from baseline; dark pink shading indicates shifts of ≥2 grades from baseline. values sum to 100% across rows for each treatment group. alt, alanine aminotransferase; ast, aspartate aminotransferase; bid, twice daily; bl, baseline; ctcae, common terminology criteria for adverse events; qd, once daily. maximum elevations over time • postbaseline incidences of alt >3× uln during weeks 0-16 were low (<2%) and comparable in all 3 treatment arms (table 4) — similar findings were observed for the weeks 0-52 period (table 5) • postbaseline incidences of ast >3× uln and ast >5× uln during weeks 0-16 were low across treatment groups (<2% and <0.5%, respectively) but greater with deucravacitinib vs placebo or apremilast (table 4) — similar findings were observed for the weeks 0-52 period (table 5) table 4. maximum elevations in alt and ast, weeks 0–16 abnormality placebo (n = 413) deucravacitinib (n = 833) apremilast (n = 419) baseline weeks 0–16 baseline weeks 0–16 baseline weeks 0–16 n (%) n (%) n (%) n (%) n (%) n (%) alt >3×->20× uln 6 (1.5) 5 (1.2) 0 9 (1.1) 1 (0.2) 2 (0.5) >5×->20× uln 2 (0.5) 3 (0.7) 0 0 0 0 >10×->20× uln 0 0 0 0 0 0 >20× uln 0 0 0 0 0 0 ast >3×->20× uln 3 (0.7) 2 (0.5) 0 13 (1.6) 0 3 (0.7) >5×->20× uln 1 (0.2) 1 (0.2) 0 3 (0.4) 0 1 (0.2) >10×->20× uln 0 0 0 0 0 0 >20× uln 0 0 0 0 0 0 patients are counted once in each relevant category. includes data from poetyk pso-1 and pso-2. for alt, the uln was defined as 33 u/l for women and 41 u/l for men. for ast, the uln was defined as 31 u/l for women and 37 u/l for men. alt, alanine aminotransferase; ast, aspartate aminotransferase; uln, upper limit of normal. table 5. maximum elevations in alt and ast, weeks 0–52 abnormality placebo (n = 658) deucravacitinib (n = 1351) apremilast (n = 419) n (%) py ir/100 py n (%) py ir/100 py n (%) py ir/100 py alt >3×->20× uln 11 (1.7) 247.0 4.5 21 (1.6) 977.0 2.1 4 (1.0) 225.8 1.8 >5×->20× uln 2 (0.3)a 249.9 0.8 6 (0.4) 983.8 0.6 0 ― ― >10×->20× uln 0 ― ― 1 (0.1) 984.7 0.1 0 ― ― >20× uln 0 ― ― 0 ― ― 0 ― ― ast >3×->20× uln 5 (0.8) 249.1 2.0 25 (1.9) 973.3 2.6 3 (0.7) 226.4 1.3 >5×->20× uln 1 (0.2) 250.2 0.4 7 (0.5) 981.9 0.7 1 (0.2) 226.8 0.4 >10×->20× uln 0 ― ― 2 (0.1) 984.4 0.2 0 ― ― >20× uln 0 ― ― 0 ― ― 0 ― ― aone patient who had an alt elevation during weeks 0-16 had a higher elevation after switching to deucravacitinib treatment and is counted with the deucravacitinib patients for the weeks 0-52 treatment period. patients are counted once in each relevant category. includes data from poetyk pso-1 and pso-2. for alt, the uln was defined as 33 u/l for women and 41 u/l for men. for ast, the uln was defined as 31 u/l for women and 37 u/l for men. alt, alanine aminotransferase; ast, aspartate aminotransferase; ir, incidence rate; py, person-years; uln, upper limit of normal. patient-level data in patients who experienced an elevation ≥3× uln during weeks 0-16 • most alt elevations ≥3× uln were transient and were often related to underlying liver conditions or concomitant medications (figure 3; table 6) • most ast elevations ≥3× uln were transient and were often related to underlying liver conditions or concomitant medications (figure 4; table 6) figure 3. alt levels over weeks 0-16 in patients with alt ≥3× ulna during weeks 0-16 400 300 100 a n al ys is v al u e ( u /l ) 200 placebo patient 12 patient 11 patient 10 patient 13 patient 14 visit 3× uln: men: 123 u/l women: 99 u/l screening baseline week 1 week 2 week 4 week 8 week 12 week 16 400 300 100 0 a n al ys is v al u e ( u /l ) 200 apremilast patient 16 patient 15 visit screening baseline week 1 week 2 week 4 week 8 week 12 week 16 3× uln: men: 123 u/l women: 99 u/l 400 300 200 100 0 a n al ys is v al u e ( u /l ) screening baseline week 1 week 2 week 4 week 8 week 12 week 16 visit deucravacitinib patient 2 patient 3 patient 1 patient 4 patient 6 patient 5 patient 7 patient 8 patient 9 3× uln: men: 123 u/l women: 99 u/l squares represent men; circles represent women. anormal adult laboratory ranges vary by test assay. for alt, the uln was defined as 33 u/l for women and 41 u/l for men. alt, alanine aminotransferase; uln, upper limit of normal. figure 4. ast levels over weeks 0-16 in patients with ast ≥3× ulna during weeks 0-16 300 200 100 0 a n al ys is v al u e ( u /l ) deucravacitinib patient 5 patient 7 patient 8 patient 9 patient 17 patient 18 patient 19 patient 20 patient 21 patient 22 patient 23 patient 24 patient 25 3× uln: men: 111 u/l women: 93 u/l visit screening baseline week 1 week 2 week 4 week 8 week 12 week 16 3× uln: men: 111 u/l women: 93 u/l 300 200 100 50 a n al ys is v al u e ( u /l ) placebo patient 11 patient 14 visit screening baseline week 1 week 2 week 4 week 8 week 12 week 16 300 200 100 0 a n al ys is v al u e ( u /l ) visit screening baseline week 1 week 2 week 4 week 8 week 12 week 16 apremilast patient 15 patient 26 patient 27 3× uln: men: 111 u/l women: 93 u/l squares represent men; circles represent women. anormal adult laboratory ranges vary by test assay. for ast, the uln was defined as 31 u/l for women and 37 u/l for men. ast, aspartate aminotransferase; uln, upper limit of normal. table 6. summary of relevant medical history and prior and concomitant medications in patients with alt or ast elevations ≥3× uln through week 16 patient id treatment timing of ≥3× uln alt increase, weeks timing of ≥3× uln ast increase, weeks relevant medical history and prior and concomitant medications through week 16 ● patient 1 deucravacitinib 12-16 ― • history of liver disease, including fatty liver disease, jaundice, possible hepatitis a, previous elevated alt, and obesity (bmi 32.3 kg/m2) • prior use of infliximab, etanercept, and methotrexate ■ patient 2 deucravacitinib 12 ― • patient bmi 32.7 kg/m2, no other relevant medical history or medications available ● patient 3 deucravacitinib screening, 1 ― • history of coronary artery disease, myocardial infarction, hypertriglyceridemia, type 2 diabetes, hypertension, bmi 33.4 kg/m2, and previous left nephrectomy • previous treatment with etanercept, clobetasol, and betamethasone dipropionate; previous and continuing treatment with metformin, aspirin, losartan, lorazepam ● patient 4 deucravacitinib 1 ― • history of hepatic steatosis and obesity (bmi 38.6 kg/m2) • no relevant medications taken before or during the event at week 1 ■ patient 5 deucravacitinib baseline 2 • history of fatty liver disease and alcohol use, bmi 30.8 kg/m2 • prior treatment with olopatadine and betamethasone butyrate propionate; prior and continuing treatment with triazolam, zolpidem tartrate ■ patient 6 deucravacitinib 8 ― • history of adipositas, bmi 37.0 kg/m 2 • previous treatment with fumaderm ■ patient 7 deucravacitinib 4 4 • bmi 29.5 kg/m 2 • previous and continuing treatment with sildenafil, beclomethasone dipropionate inhaler ● patient 8 deucravacitinib 16 16 • history of kawasaki’s disease and hypertension, bmi 17.0 kg/m2 • alcohol use was not reported in the parent study, but during the long-term extension study the investigator reported an ae of alcohol dependence syndrome • an abdominal ct done for ae of acute abdomen on day 74 revealed hepatic steatosis • history of clobetasol propionate, betamethasone butyrate propionate, prednisolone valerate acetate, metroclopramine hydrochloride, solyugen, acetaminophen, iohexol, esomeprazole magnesium hydrate ● patient 9 deucravacitinib 16 16 • bmi 37.4 kg/m2 • previous treatment with acetic acid, dexamethasone, neomycin sulfate, otomize ear spray; previous and continuing treatment with depo-provera ■ patient 10 placebo baseline, 1 ― • history of fatty liver disease, latent tuberculosis, tinea versicolor, liver function elevations, prediabetes mellitus, gout, and hyperlipidemia, bmi 26.0 kg/m2 • previous treatment with methotrexate, cyclosporine, neotigason; previous and continuing treatment with legalon, tiropramide hydrochloride, febuxostat, cilostazol, crovatin, trimebutine maleate, buspirone hydrochloride, pyridoxine, isoniazid ● patient 11 placebo screening, 12 12 • history of transaminitis, bmi 37.6 kg/m2 • previous and ongoing use of intrauterine contraception device ● patient 12 placebo screening, 1, 4 ― • history of elevated alt and ast, hypertension, bmi 35.8 kg/m2 • previous treatment with secukinumab; previous and ongoing treatment with nedal, karnidin, jaydess, hepa-merz 3000, and furaginum ● patient 13 placebo baseline, 1, 2, 4 ― • history of hepatic steatosis, latent tuberculosis, intermittent elevated liver function tests, hair-an syndrome, and obesity (bmi 37.0 kg/m2) • previous treatment with rifampin; previous and continuing treatment with ibuprofen ■ patient 14 placebo screening, baseline, 1, 2, 4, 8 baseline, 1, 2, 4, 8 • history of elevated alt and ast, and benign prostatic hyperplasia, bmi 26.6 kg/m2 • previous treatment with ixekizumab, guselkumab, amitriptyline, ciprofloxacin; treatment with sulfamethoxazole and trimethoprim (days 11-16 and days 29-39) ● patient 15 apremilast screening, 12 12 • bmi 33.0 kg/m2, no other relevant medical history or medications available ■ patient 16 apremilast 16 ― • bmi 28.1 kg/m 2 • prior treatment with levocetirizine dihydrochloride ● patient 17 deucravacitinib ― screening, 8 • history of helicobacter pylori-positive serum antibody, type 2 diabetes, and hypertension, bmi 32.6 kg/m2 • previous treatment with tepilamide fumarate or placebo (as part of a clinical trial), omeprazole, clarithromycin, amoxicillin; previous and continuing treatment with ancef, lisinopril, amitriptyline, metformin ■ patient 18 deucravacitinib ― 8 • bmi 33.0 kg/m 2 • previous treatment with adalimumab and ustekinumab ■ patient 19 deucravacitinib ― 12 • bmi 50.7 kg/m2, no other relevant medical history or medications available ■ patient 20 deucravacitinib ― 16 • bmi 43.4 kg/m2, no other relevant medical history or medications available ■ patient 21 deucravacitinib ― 4 • bmi 27.2 kg/m 2 • previous treatment with methotrexate ● patient 22 deucravacitinib ― 2 • bmi 26.4 kg/m2 • previous and continuing treatment with ethinyl estradiol/etonogestrel ■ patient 23 deucravacitinib ― 12 • history of penicillin allergy, hypercholesterolemia, occasional heavy alcohol consumption, and hypertension, bmi 25.7 kg/m2 • previous treatment with guselkumab, doxycycline (taken from day 72 to day 81); previous and continuing treatment with aspirin, amlodipine/benazepril, rosuvastatin ■ patient 24 deucravacitinib ― 2 • history of coronary artery disease, smoking, stent insertion (3 stents total), and arterial hypertension, bmi 27.6 kg/m2 • previous and continuing treatment with coversyl, bisoprolol, lipitor, and acetylsalicylic acid ■ patient 25 deucravacitinib ― 8, 12 • bmi 28.9 kg/m2 • previous and ongoing treatment with lisinopril, patient-reported excessive alcohol intake while in the long-term extension study ■ patient 26 apremilast ― 2 • bmi 31.2 kg/m 2 • previous treatment with brodalumab ■ patient 27 apremilast ― 1, 8, 12 • history of hepatic steatosis, high liver function tests, hyperlipidemia, hypertension, bmi 35.3 kg/m2, and renal cyst (left) • previous treatment with neotigason; previous and continuing treatment with perindopril and indapamide squares represent men; circles represent women. ae, adverse event; alt, alanine aminotransferase; ast, aspartate aminotransferase; bmi, body mass index; ct, computed tomography; uln, upper limit of normal. conclusions • in the poetyk pso-1 and pso-2 trials in patients with moderate to severe plaque psoriasis, shifts >1 ctcae grade from baseline in alt and ast were infrequent over weeks 0–16 with deucravacitinib treatment — there were no shifts to grade 4 and only 2 shifts to grade 3 (1 each with deucravacitinib and apremilast treatment) • in patients treated with deucravacitinib, increases in alt and ast >3× uln were observed in <2% of patients over 52 weeks • alt and ast increases to >3× uln were mainly transient, and most were related to underlying liver conditions or concomitant medications • there were no cases of drug-induced liver injury references 1. burke jr, et al. sci transl med. 2019;11:eaaw1736. 2. sotyktu™ (deucravacitinib) [package insert]. princeton, nj: bristol-myers squibb company; september 2022. 3. wrobleski st, et al. j med chem. 2019;62:8973-8995. 4. armstrong aw, et al. j am acad dermatol. 2023;88:29-39. 5. strober b, et al. j am acad dermatol. 2023;88:40-51. 6. thaçi d, et al. presented at the 30th eadv congress; september 29–october 2, 2021. 7. winthrop kl. nat rev rheumatol. 2017;13:234-243. acknowledgments • this study was sponsored by bristol myers squibb • writing and editorial assistance was provided by liz rockstein, phd, of peloton advantage, llc, an open health company, parsippany, nj, usa, funded by bristol myers squibb disclosures • ml: research funds on behalf of mount sinai: abbvie, amgen, arcutis, avotres, boehringer ingelheim, dermavant, eli lilly, incyte, janssen, ortho dermatologics, regeneron, and ucb; consultant: aditum bio, almirall, altrubio, anaptysbio, arcutis, arena, aristea, arrive technologies, avotres, biomx, boehringer ingelheim, brickell biotech, bristol myers squibb, cara therapeutics, castle biosciences, corevitas’ (corrona) psoriasis registry, dermavant, dr reddy’s laboratories, evelo biosciences, evommune, forte biosciences, helsinn therapeutics, hexima, leo pharma, meiji seika pharma, mindera, pfizer, seanergy, and verrica • ae: research funding: abbvie, boehringer ingelheim, bristol myers squibb, eli lilly, janssen, novartis, and pfizer; honoraria as consultant and/or speaker: abbvie, almirall, boehringer ingelheim, bristol myers squibb, dermavant, eli lilly, galápagos nv, galderma, horizon therapeutics, janssen, leo pharma, mcneil consumer healthcare, mylan, novartis, pfizer, samsung bioepis co, sun pharma, ucb, union, and zuellig pharma ltd • ml, sb, and rmk: employees and shareholders: bristol myers squibb • kh: consultant: bristol myers squibb • bs: consultant (honoraria): abbvie, almirall, amgen, arcutis, arena, aristea, asana, boehringer ingelheim, bristol myers squibb, connect biopharma, dermavant, eli lilly, equillium, glaxosmithkline, immunic therapeutics, janssen, leo pharma, maruho, meiji seika pharma, mindera, novartis, ortho dermatologics, pfizer, regeneron, sanofi genzyme, sun pharma, ucb, ventyxbio, and vtv therapeutics; speaker: abbvie, eli lilly, janssen, and sanofi genzyme; co-scientific director (consulting fee): corevitas' (corrona) psoriasis registry; investigator: abbvie, cara therapeutics, corevitas' (corrona) psoriasis registry, dermavant, dermira, and novartis mailto:lebwohl%40aol.com?subject= slide 1  the full analysis set (fas) included 200 subjects. of these, 53 subjects were in dfd-29 (40 mg) group, 47 in dfd-29 (20 mg), 48 in doxycycline (40 mg) and 52 in the placebo group.  the proportion of subjects achieving iga treatment success was 66.04% in dfd-29 (40 mg), 33.33% in doxycycline (40 mg), 31.91% in dfd-29 (20 mg) and 11.54% in the placebo group (fig.1) highly statistically significant treatment differences (p<0.0001) were demonstrated for dfd-29 (40 mg) vs placebo and doxycycline (40 mg), as well as for dfd-29 (20 mg) versus placebo. highly statistically significant treatment differences were demonstrated for dfd-29 (40 mg) versus placebo (p<0.0001), versus doxycycline 40 mg (p=0.0010) and versus dfd-29 (20 mg) (p=0.0007).  the mean reduction in total inflammatory lesion count from baseline was 19.2 lesions in dfd-29 (40 mg), 12.6 lesions in dfd-29 (20 mg), 10.5 lesions in doxycycline (40 mg) and 7.3 lesions in placebo groups (fig.2). highly statistically significant treatment differences were demonstrated for dfd-29 (40 mg) versus placebo (p<0.0001), versus doxycycline (p=0.0004) and versus dfd-29 (20 mg) (p=0.0070).  the proportion of subjects experiencing at least one teae was 73.58% in dfd-29 (40 mg), 83.33% in dfd-29 (20 mg), 77.08% in doxycycline (40 mg) and 67.31% in the placebo groups. overall, most of the reported teaes were of mild or moderate intensity and were not or possibly related to the study treatment per investigator.  the ofm study demonstrated that dfd-29 (40 mg) and oral doxycycline 40 mg, provide similar dermal interstitial space fluid (disf) levels of minocycline and doxycycline, respectively. dfd-29, a low dose oral minocycline, demonstrates superior efficacy as compared to placebo and oraycea® capsules (doxycycline hcl) in subjects with papulopustular rosacea athanasios tsianakas, md1 ; neal bhatia, md2; shanavas alikunju, phd3; anirudh gautam, mpharm4; srinivas shenoy, md5; preeti singh, md5; srinivas sidgiddi, md5 1fachklinik bad bentheim, germany, director of clinical dermatology, 2 therapeutics clinical research, san diego, ca, 3dr. reddy’s laboratories ltd., hyderabad, india, 14dr. reddy’s laboratories sa, basel, switzerland, 5dr. reddy’s laboratories inc., princeton, nj introduction  rosacea is a chronic, inflammatory skin disease that affects primarily the cheeks, nose, chin, and forehead, mainly in adults. papulopustular rosacea is the second most common subtype. conclusions  dfd-29, low dose minocycline, could become another option in treatment of inflammatory lesions of rosacea, for patients with mild, moderate or severe rosacea.  despite similar disf levels, dfd-29 (40 mg) has greater efficacy compared to doxycycline 40 mg, probably due to greater lipophilicity resulting in higher intracellular concentrations. methods figure 1. iga success at week 16  in a phase 2, randomized, double-blind, parallel group trial enrolling adults (n=205) with mild, moderate or severe papulopustular rosacea, subjects were randomized to receive dfd-29 (minocycline hcl), 40 mg extended release (er) capsules, dfd-29, 20 mg er capsules, oraycea® (doxycycline hcl), 40 mg capsules (antiinflammatory dose with modified release) or placebo, one capsule a day for 16 weeks.  the co-primary endpoints were proportion of subjects achieving treatment success (iga – ‘0’/ ‘1’ with ≥ 2-grade reduction), and mean reduction in total inflammatory lesion counts at week 16 compared, in the dfd-29 compared to placebo and doxycycline groups.  an earlier phase 1 study, the dermal interstitial space fluid (disf) levels of doxycycline and minocycline were measured, using open-flow microperfusion (ofm) in healthy human subjects. financial support: this study was funded and sponsored by the dr. reddy’s laboratories group of companies, princeton, nj, 08540, usa. drl publication # 884 results figure 2. mean reduction in total inflammatory count at week 16 -25 -20 -15 -10 -5 0 dfd29 40mg, n=53 dfd-29 20mg, n=47 doxycycline 40mg, n=48 placebo, n=52 m e a n r e d u c ti o n i n t o ta l in fl a m m a to ry c o u n t -19.2 -10.5 -7.3 -12.6 * * # @ 0 10 20 30 40 50 60 70 80 90 100 iga(0/1) dfd-29 40mg, n=53 dfd-29 20mg, n=47 doxycycline 40mg,n=48 placebo, n=52 % s u b je c ts a c h ie v in g i g a s u c c e s s 66.4 33.3 31.9 11.5 * # @ * *statistical significance reported vs placebo, # statistical significance reported vs doxycycline, @ statistical significance reported vs dfd-29 20mg neal bhatia, m.d. therapeutics clinical research, san diego, ca introduction • imiquimod is an immune response modifier that is fda approved for the treatment of actinic keratosis (aks), external genital warts, and superficial basal cell carcinoma.1 • imiquimod is a potent inducer of interferon (ifn)-α and other pro-inflammatory cytokines.2 • some patients treated with topical imiquimod develop influenza-like symptoms (e.g., myalgia, malaise, headache, low-grade fever, and fatigue) that may be related to elevated levels of pro-inflammatory cytokines associated with application of the drug.3 • this study was carried out to assess correlations between influenza-like symptoms and cytokine levels in patients who applied imiquimod cream to their skin for 14 days. other variables that might influence emergence and severity of symptoms, including age, severity of local skin reactions, the amount of surface area involved, and the area of the body exposed were also evaluated. methods design • single-center open-label study. subjects • 22 men and women with 5-20 aks between 30 and 89 years of age. treatment • the designated treatment area (entire face or balding scalp; or chest or upper extremities) was cleansed with an approved cleanser and allowed to dry for 5 minutes prior to application of imiquimod 3.75% cream to a total are of 200 cm2. the treatment period was 14 days. endpoints • clearance of aks. • frequency of symptoms indicative of an influenza-like response, including, fever, headache, fatigue, malaise, gastrointestinal symptoms, dizziness, myalgia, and arthralgia. • change from baseline at subsequent study visits (days 8, 15, 43, and 57 [end of study]) in: • cytokines – interleukin (il) -6, il-8, il-12, il-13, il-2 receptor (r), tumor necrosis factor-α (tnf), ifn-α, and ifn-γ • frequency of local skin reactions of erythema, scabbing/crusting, edema, erosion/ulceration, exudate, flaking/scaling/dryness and pruritus. results subjects • characteristics of subjects enrolled and areas treated are summarized in table 1. clearance of aks • all but one subject experienced either complete clearance or partial clearance of actinic keratoses with no more than 3 remaining in the treatment field. table 1. subject characteristics characteristic n=22 age (years) mean (standard deviation) 62.8 (8.99) median 59 age group, n (%) ≥30 years to ≤59 years 12 (54.5) ≥60 years to ≤ 89 years 10 (45.5) sex, n (%) female 7 (31.8) male 15 (68.2) area of treatment n (%) entire face or balding scalp 11 (50.0%) chest or upper extremities 11 (50.0%) frequency of influenza-like symptoms • systemic symptoms characteristic of influenza occurred infrequently during the treatment period (table 2). table 2. influenza-like symptoms that emerged during treatment symptom occurrence during treatment (n) fever 1 myalgia 1 fatigue 0 malaise 1 headache 4 gastrointestinal symptoms 3 dizziness 3 arthralgia 3 relationship between clearance of aks and influenza-like symptoms • there was no apparent relationship between clearance on the occurrence of symptoms (table 3). table 3. ak clearance in subjects with and without influenza-like symptoms systemic symptoms during treatment baseline ak count, mean (median) end of treatment ak count, mean (median) yes 14.0 (14.0) 2.9 (0.0) no 13.7 (14.0) 2.4 (1.0) changes from baseline in cytokine levels • twelve subjects had elevations in at least one cytokine at one or more post-baseline visits (table 4). • there were no apparent relationships between the occurrences of cytokine elevations and either the occurrence of influenza-like symptoms or local skin reactions (figure 1). table 4. cytokine elevations during treatment. subject visit 1 visit 2 visit 3 visit 4 4 il-2 il-2 il-2, il-13 il-2, il-2r, il-13 7 il-13 il-13 8 ifn-γ ifn-γ ifn-γ ifn-γ 10 il-2, il-12 il-2 il-2, il-12, ifn-γ 11 il-6, il-2r, il-13 il-6, il-2r, il-13 il-6, il-2r, il-13 12 il-13 13 il-13 il-13 15 il-8, il-13 18 il-13 20 il-13 il-13 21 il-13 il-12 23 il-8 il-13 il-13 figure 1. temporal relationships among systemic symptoms (ss), local skin reactions (lsr) and elevations in cytokines (el cyt) for patients with and without ss. no systemic symptoms systemic symptoms v1 v2 v3 v4 v5 v1 v2 v3 v4 v5 ss lsr el cyt ss lsr el cyt ss lsr el cyt ss lsr el cyt ss lsr el cyt ss lsr el cyt ss lsr el cyt ss lsr el cyt ss lsr el cyt ss lsr el cyt ss lsr el cyt ss lsr el cyt ss lsr el cyt conclusion • treatment on the face led to more incidence of flu like symptoms in younger patients • elevations in pro-inflammatory cytokines did not appear to predict the development of either systemic symptoms or local skin reactions. • elderly patients treated on the body were less likely to develop reactions of the four groups. references 1. imiquimod cream. 2010. https://www.accessdata.fda.gov/drugsatfda_docs/ label/2010/020723s022lbl.pdf. 2. nerurkar l, et al. sci rep. 2017;7:16570. 3. cantisani c, et al. recent pat inflamm allergy drug discov. 2012;6:65-69. acknowledgments the author would like to recognize the contributions of aramed strategies inc for scientific analysis and editorial support. study funding was graciously provided by ortho dermatologics. • empty boxes (gray): subject • yellow boxes: subject had no symptoms with a score of 2 or more. • pink boxes: subject had at most one symptom scored a 2 (moderate) and no symptoms scored above 2. • red boxes: subject had more than one symptom scored at two or more or at least one symptom scored as a 3 (severe). measuring the predictive value of serological quantification of cytokines with the onset of influenza-like signs and symptoms induced by imiquimod 3.75% cream: results of a single center, open-label, proof of concept trial lilly immunology impact of day-to-day sleep disruption on the burden of disease in moderate-severe adult atopic dermatitis patients evangeline pierce,1 c. elise kleyn,2 susanne grond,1 jenny austin,3 catherine reed,1 sonja ständer 4 1eli lilly and company, indianapolis, in, usa; 2the dermatology centre, salford royal nhs foundations trust, manchester nihr biomedical research centre, the university of manchester, university of manchester, manchester, uk; 3adelphi real world, bollington, uk; and 4university hospital münster, münster, germany methods data source  data were drawn from the adelphi atopic dermatitis disease specific programme (dsptm), a multinational, point in time survey of physicians (dermatologists, allergists and pcps) and their consulting ad patients in the us (during 2018), germany (2019), italy (2019), uk (2019), france (2020) and spain (2021).  the study used data from adults aged ≥18 years with physician-assessed moderate-to-severe ad. patient-reported outcomes  patients completed pro questionnaires in which they were asked to select ongoing day-to-day symptoms they usually experienced (not related to a flare) from a list including s-d, itch, skin pain, anxiety, and depression/low mood, and to rate the symptom frequency.  two patient groups were evaluated: those with frequent s-d (all the time/regularly) and those with infrequent s-d (sometimes/rarely/none). table 1. physician-reported demographics and clinical characteristics for adults with moderate-tosevere ad according to the frequency of s-d. disclosures s ständer has declared consulting fees from: beiersdorf, bellus health, benevolent, bionorica, clexio, escient, galderma, grünenthal, lilly, menlo, pfizer, sanofi, trevi, and vifor, and honoria/speaker fees from: abbvie, almirall, galderma, grünenthal, leo, lilly, menlo, pfizer, sanofi, trevi, p.g. unna academy, and vifor plough, abbott, janssen and creabilis. e kleyn has declared honoraria/ad hoc consultancy payments from janssen, eli lilly, leo, novartis, abbvie, ucb and almirall as well as research funding from pfizer, novartis, janssen and eli lilly. j austin is an employee of adelphi real world c reed, s grond and e pierce are employees of eli lilly and company this analysis was sponsored by eli lilly and company. this study is previously presented at american academy of dermatology (aad); boston, usa; 25-29 march 2022 study was sponsored by eli lilly and company background ■ atopic dermatitis (ad) is a common inflammatory skin disease with symptoms including itching, dry, red and scaly skin. ■ itch and associated skin pain can frequently lead to sleep disruption (s-d) among patients with ad with resulting daytime fatigue and disturbed cognition.1, 2 ■ while recent studies have demonstrated a link between higher ad severity and reduced sleep quantity and quality,3 real-world data for ad from the patient perspective is still limited and the role of s-d frequency and its impact on patient quality of life (qol) requires further exploration. key results winter clinical dermatology conference; hawaii, usa; january 13-18, 2023 figure 2. wpai due to ad in moderate-to-severe adult ad patients according to the frequency of s-d. figure 3. mean dlqi and poem scores in moderate-to-severe adult ad patients according to the frequency of s-d. figure 1. patient-reported day-to-day symptoms in moderate-to-severe adult ad patients according to the frequency of s-d. scan or click the qr code or use this url (https://lillyscience.lilly.com/congress/ wcdc2023) for a list of all lilly content presented at the congress. other company and product names are trademarks of their respective owners. all patients (n=719) frequent s-d (n=162) infrequent s-d (n=557) p-value mean age (years) 38.5 ± 14.5 37.0 ± 14.5 38.9 ± 14.4 0.142 male, n (%) 347 (48.3%) 83 (51.2%) 264 (47.4%) 0.390 body mass index (kg/m2) 25.7 ± 13.4 26.9 ± 27.2 25.3 ± 4.1 0.175 psychological comorbidities, n (%) anxiety depression 132 (18.4%) 69 (9.6%) 29 (17.9%) 18 (11.1%) 103 (18.5%) 51 (9.2%) 0.864 0.457 employeda, n (%) 549 (64.6%) 97 (60.2%) 362 (65.8%) 0.194 time since ad diagnosis (years)b 10.9 ± 12.1 12.3 ± 11.9 10.5 ± 12.1 0.192 current easi score 9.9 ± 8.0 12.2 ± 10.0 9.2 ± 7.3 <0.001 current bsa affected (%)c 23.7 ± 16.2 24.5 ± 17.1 23.5 ± 16.0 0.512 results are presented as mean ± standard deviation unless stated otherwise an=711, 161 and 550 for the three groups, respectively; bn=433, 98 and 335 for the three groups, respectively; cn=627, 140 and 487 for the three groups, respectively ad, atopic dermatitis; s-d, sleep disruption results  719 patients with a physician assessment of moderate or severe ad completed the pro questionnaire and were included in this analysis o 22.5% experienced day-to-day frequent s-d and 77.5% infrequent s-d.  table 1 shows patient demographics and clinical characteristics.  patients with patient-reported day-to-day frequent s-d were significantly more likely to experience frequent itch, skin pain, anxiety and depression than those with infrequent s-d (figure 1). conclusions ■ more than one fifth of moderate-to-severe adult ad patients experience s-d regularly or all the time. ■ compared with infrequent s-d patients, frequent s-d patients have significantly more frequent day-to-day itch and are also more likely to experience skin pain, anxiety and depression more frequently. ■ patients with frequent s-d have greater activity/work productivity impairment and higher disease burden. ■ these results reinforce the link between itch, skin pain, anxiety, and depression with s-d. and underline the importance of sleep for patient’s qol.  the patient questionnaire included the following validated pro assessments: o patient orientated eczema measure (poem)4,5 o dermatology life quality index (dlqi)6 o work productivity and activity impairment (wpai)7  statistical comparisons for the two patient groups were made using pairwise t-tests for continuous variables and chi-squared for categorical variables. ■ overall work and activity impairment due to ad was significantly increased in patients with frequent s-d than those with infrequent s-d, as shown in figure 2. ■ figure 3 shows burden of disease on qol and ad symptoms was higher for patients with frequent versus infrequent s-d. objective  to assess the impact of day-to-day (not related to a flare) s-d frequency on patients with moderate-tosevere ad using patient-reported outcomes (pros). strengths and limitations strengths adelphi dsps provide data from large international databases, providing realworld information on disease characteristics, management and outcomes limitations assessment of ad severity was not based on a standardized definition but utilised physician judgement. the s-d definition was based on patient-report rather than a standardised measure and rated in terms of frequency and not intensity. the study was limited by factors associated with any survey, such as accurate recall and variability in the interpretation of questions point-in-time design therefore cannot be used to demonstrate cause and effect references 1. maarouf m, et al. dermatitis.2018;29:278-281. 2. yu sh, et al. dermatitis. 2016;27:50-58. 3. bruin-weller m, et al. j dermatolog treat. 2021;32:164-173. 4. charman cr, et al. arch dermatol. 2004;140:1513⎼9. 5. charman cr, et al. br j dermatol. 2013;169:1326⎼32. 6. finlay ay, khan gk. clin exp dermatol. 1994;19:210⎼6. 7. reilly mc, et al. pharmacoecomics. 1993;4:353⎼65. slide number 1 ¾ the f-c formulation had the highest retention of betamethasone in the skin and the highest 12-hour and 24-hour permeation of betamethasone through the skin into the receptor fluid. ¾ the f-10 formulation had the second highest retention of betamethasone in total skin and relatively low permeation of betamethasone into the receptor fluid (figure 2). ¾ the f-10 formulation had skin layer betamethasone concentrations of 33 ng, 18 ng, and 14 ng in the stratum corneum, epidermis, and dermis, respectively (figure 1). ¾ the skin layer concentrations of the f-c formulation were 37 ng, 43 ng, and 34 ng, and those of the f-a formulation were 5 ng, 17 ng, and 14 ng in the stratum corneum, epidermis, and dermis (figure 1). ¾ the formulation with the best balance of penetration, permeation, retention, and low absorption (f-10/dfd-01) was selected for additional evaluation. permeation analysis of novel steroid vehicles to deliver and retain steroid in skin layers associated with psoriasis leon kircik, md1; franklin okumu, phd2; sateesh kandavilli, phd2 1dermresearch, pllc, louisville, ky; 2promius pharma, a subsidiary of dr. reddy’s laboratories, princeton, nj introduction ¾ it is possible to tailor the formulation of topical treatment vehicle to facilitate delivery of active drug to the site of skin disease pathology. ¾ psoriasis is a condition primarily affecting the epidermal layers of the skin. developing a vehicle that optimizes steroid delivery to the affected psoriatic skin layers, while reducing permeation of the steroid into the systemic circulation could be beneficial in the treatment of psoriasis. ¾ this study was designed to evaluate various vehicle formulations on the penetration and retention of betamethasone dipropionate in the skin to identify the formulation with the best balance of penetration into the epidermis and low systemic absorption. conclusions ¾ the f-10 (dfd-01) formulation containing oleyl alcohol, sorbitan monostearate, polyoxyl 20 cetostearyl ether, cetostearyl alcohol, and mineral oil, demonstrated a good balance of betamethasone retention in the skin, with low systemic absorption. ¾ this vehicle is designed to achieve retention of steroid in skin layers to maximize local efficacy while minimizing systemic absorption of steroid. methods figure 1. penetration of total betamethasones after 24 hours ¾ a base vehicle formulation containing water, sorbitan monostearate, polyoxyl 20 cetostearyl ether, cetostearyl alcohol, mineral oil, propylparaben, methylparaben, butylated hydroxyl toluene, and hydroxyethyl cellulose was developed. ¾ all formulations contained betamethasone dipropionate, 0.05%. vehicle formulation variants included eladiyl alcohol (f-a), hexanol (f-b), dodecanol (f-c), octadecanol (f-d), docosanol (f-e), or oleyl alcohol (f-10). ¾ test agents were applied to human cadaver skin in static franz-cell chambers containing receptor fluid (4% bsa and 0.01% gentamicin). permeation of betamethasone into the receptor fluid was measured at 0, 2, 6, 10, 12 and 24 hours. at 24 hours, the distribution of betamethasone and its metabolites in the stratum corneum, epidermis, and dermis was analyzed using lc-ms/ms. financial support: this study was funded and sponsored by the dr. reddy’s laboratories group of companies. drl publication # 787 results figure 2. retention of total betamethasones after 24 hours fc17posterpromiuskircikpermeation.pdf acknowledgements: medical writing support was provided by prescott medical communications group (chicago, il) with financial support from ortho dermatologics; ortho dermatologics is a division of bausch health us, llc presented at winter clinical dermatology conference 2020 • january 17-22, 2020 • kohala coast, hi synopsis ◾ psoriasis is a chronic, immune-mediated disease that can have frequent exacerbations and remissions1 ◾ topical corticosteroids are the mainstay of psoriasis treatment, particularly for mild disease,2 while systemic therapies may be useful in patients with severe disease; however, topical treatments are having an increasing role in moderate-to-severe psoriasis as an integral part of combination therapy ◾ a novel halobetasol propionate (hp) 0.01% lotion (bryhali® ortho dermatologics, bridgewater, nj) has demonstrated efficacy versus vehicle in two phase 3 studies of patients with moderate-to-severe plaque psoriasis3,4 ◾ few studies have examined the efficacy and safety of topical therapies for the treatment of psoriasis in hispanic patients objective ◾ to evaluate the efficacy, safety, and tolerability following once-daily application of hp 0.01% lotion in hispanic patients with moderate-to-severe plaque psoriasis methods ◾ in two phase 3, multicenter, double-blind studies, patients were randomized 2:1 to receive hp 0.01% or vehicle lotion once-daily for 8 weeks, with a 4-week posttreatment follow-up3,4 • at baseline, patients were required to have an investigator global assessment (iga) score of 3 or 4 (5-point scale; 0=clear and 4=severe) and affected body surface area (bsa) of 3% to 12% • in these studies, cerave® hydrating cleanser and cerave® moisturizing lotion (l’oreal, ny) were provided as needed for optimal moisturization/cleaning of the skin ◾ data from these two studies were pooled and analyzed post hoc in a subset of self-identified hispanic participants ◾ efficacy assessments were as follows: • overall treatment success (≥2-grade improvement from baseline in iga score and a score of ‘clear’ or ‘almost clear’ [primary endpoint]) • treatment success (≥2-grade improvement from baseline) in each individual sign of psoriasis (erythema, plaque elevation, and scaling) at the target lesion • improvements from baseline in overall bsa • reductions of ≥50% and ≥75% from baseline in igaxbsa (igaxbsa-50, igaxbsa-75) ◾ safety and treatment-emergent adverse events (teaes) were evaluated throughout the study results ◾ this analysis included 119 hispanic participants (hp 0.01% lotion, n=76; vehicle, n=43) ◾ at week 8, significantly more hp-treated participants achieved overall treatment success compared with vehicle-treated participants; this significant difference was achieved as early as week 4 and sustained posttreatment (figure 1) figure 1. overall treatment successa by study visit in hispanic participants (itt population, pooled) 50% 60% 70% 40% 30% 20% 10% 0% 0 2 4 6 8 12 p e rc e n ta g e o f p a rt ic ip a n ts treatment posttreatment 6.6% 18.4% 33.1% 25.2% 10.2% 0% 0% 4.7% 10.3% 38.8% study visit (weeks) hp 0.01% lotion (n=76) vehicle (n=43) *p<0.05 vs vehicle; ***p≤0.001 vs vehicle. atreatment success was defined as a ≥2-grade improvement from baseline in iga score and a score of ‘clear’ or ‘almost clear’ (0 or 1). hp, halobetasol propionate; iga, investigator global assessment; itt, intent-to-treat. efficacy and safety of halobetasol propionate 0.01% lotion in the treatment of moderate-to-severe plaque psoriasis in a hispanic population: post hoc analysis of two phase 3 randomized controlled trials ◾ participants treated with hp 0.01% lotion achieved a significantly greater mean percent reduction from baseline in affected bsa at week 8 versus those treated with vehicle, with significant differences observed as early as week 2 (figure 3) figure 3. mean percent reduction in overall affected body surface area (bsa) by study visit in hispanic participants (itt population, pooled) -10% 0% 10% -20% -30% -40% 0 2 4 6 8 12 p e rc e n t c h a n g e f ro m b a se li n e treatment posttreatment -4.9% -14.6% -23.3% -26.0% -11.3% 5.0% -0.8% 1.6% -9.7% -33.1% study visit (weeks) hp 0.01% lotion (n=76) vehicle (n=43) * p<0.05 vs vehicle; ** p≤0.01 vs vehicle; *** p≤0.001 vs vehicle. hp, halobetasol propionate; itt, intent-to-treat. ◾ at week 8, a clinically meaningful effect in overall psoriasis treatment was achieved by participants treated with hp 0.01% lotion versus those with vehicle (figure 4) figure 4. achievement of ≥50% (igaxbsa-50) and ≥75% (igaxbsa-75) reduction in igaxbsa at week 8 in hispanic participants (itt population, pooled) 70% 60% 50% 40% 30% 20% 10% 0% 51.3% 16.3% igaxbsa-50 36.8% 11.6% igaxbsa-75 hp 0.01% lotion (n=76) vehicle (n=43) p e rc e n ta g e o f p a rt ic ip a n ts **p<0.01 vs vehicle; ***p<0.001 vs vehicle. bsa, body surface area; hp, halobetasol propionate; iga, investigator global assessment; itt, intent-to-treat. ◾ treatment-related teaes with hp 0.01% lotion through week 8 were application site infection and application site dermatitis (n=1 each); the one treatment-related teae with vehicle was psoriasis ◾ conclusions ◾ halobetasol propionate 0.01% lotion was associated with significant, rapid, and sustained reductions in disease severity in a hispanic population with moderate-to-severe psoriasis, with few treatment-related teaes over 8 weeks of once-daily use references 1. nestle fo, et al. n engl j med. 2009;361(5):496-509. 2. menter a, et al. j am acad dermatol. 2009;60(4):643-659. 3. sugarman jl, et al. cutis. 2019;103(2):11-116. 4. green lj, et al. j drugs dermatol. 2018;17(10):1062-1069. author disclosures: seemal r. desai has served as a research investigator and/or consultant for skinmedica, ortho dermatologics, galderma, pfizer, dermavant, almirall, dermira, and watson. brad glick has served as investigator, advisor, and/or speaker for abbvie, celgene, janssen, sun pharma, lilly, novartis, dermira, sanofi/genzyme, regeneron, pfizer, dermavant, chemocentryx, and ortho dermatologics; and is a stockholder in top md. james q del rosso has served as a consultant, investigator, and speaker for ortho dermatologics. tina lin is an employee of ortho dermatologics and may hold and/or stock options in its parent company. ◾ psoriasis signs were also reduced at week 8, with more hp-treated participants achieving ≥2-grade improvement in erythema, plaque elevation, and scaling at the target lesion compared with vehicle (figure 2) • significant differences versus vehicle were observed in all signs of psoriasis as early as week 4 figure 2. treatment successa in psoriasis signs of erythema (a), plaque elevation (b), and scaling (c) at the target lesion by study visit in hispanic participants (itt population, pooled) 50% 60% 70% 40% 30% 20% 10% 0% 0 2 4 6 8 12 50% 60% 70% 40% 30% 20% 10% 0% 0 2 4 6 8 12 50% 60% 70% 40% 30% 20% 10% 0% 0 2 4 6 8 12 p e rc e n ta g e o f p a rt ic ip a n ts a. erythema treatment posttreatment 10.5% 28.1% 42.4% 34.2% 15.6% 0.2% 2.5% 3.5% 12.9% 49.1% p e rc e n ta g e o f p a rt ic ip a n ts b. plaque elevation treatment posttreatment 15.9% 36.8% 45.3% 44.5% 23.9% 8.0% 14.7% 16.7% 25.1% 53.0% p e rc e n ta g e o f p a rt ic ip a n ts c. scaling treatment posttreatment 22.4% 40.4% 50.6% 41.8% 28.6% 7.3% 12.9% 14.6% 23.9% 57.7% study visit (weeks) hp 0.01% lotion (n=76) vehicle (n=43) study visit (weeks) hp 0.01% lotion (n=76) vehicle (n=43) study visit (weeks) hp 0.01% lotion (n=76) vehicle (n=43) *p<0.05 vs vehicle; **p<0.01 vs vehicle; ***p<0.001 vs vehicle. atreatment success was defined as a ≥2-grade improvement from baseline in each individual sign of psoriasis at the target lesion. hp, halobetasol propionate; itt, intent-to-treat. seemal r desai, md1; brad glick, do, mph2; james q del rosso, do3; tina lin, pharmd4 1innovative dermatology, pa, plano, tx and the university of texas southwestern medical center, dallas, tx; 2gsi clinical research, margate, fl; 3jdr dermatology research/thomas dermatology, las vegas, nv; 4ortho dermatologics*, bridgewater, nj *ortho dermatologics is a division of bausch health us, llc. the psychological impacts of horizontal frontalis lines, glabellar lines, and lateral canthal lines: qualitative, patient-centered studies steven dayan, md1; steven g. yoelin, md2; koenraad de boulle, md3; ilia l. ferrusi, phd4 1denova research, chicago, il, usa; 2medical associates inc., newport beach, ca, usa; 3aalst dermatology clinic, aalst, belgium; 4allergan plc, irvine, ca, usa scan to obtain pdf of poster introduction • facial lines or wrinkles are a common sign of aging, developing slowly over time due to repeated contraction of underlying facial muscles1-3 • in the upper face, 3 types of facial lines are common: lateral canthal lines (crow’s feet lines; cfl), caused by smiling or squinting; horizontal frontalis lines (forehead lines; fhl), caused by raising of the eyebrows; and glabellar lines (gl), caused by frowning1 • with age, these upper facial lines (ufl) tend to become static and visible, even when facial muscles are at rest1 • the development of ufl can influence self-perception and may have a variety of psychological impacts3-5 objective • to determine the psychological impact of cfl and fhl individually and of the 3 ufl areas combined • to evaluate whether the 11-item facial line outcomes (flo-11) questionnaire3 is an adequate measure to assess cfl, fhl, and ufl psychological impacts methods subjects • two qualitative research studies (figure 1) were conducted in adults with moderate or severe ufl (ie, cfl, fhl, and gl) at maximum contraction, as measured using the investigator-rated facial wrinkle scale with photonumeric guide (fws; 0=none; 1=mild; 2=moderate; 3=severe) • study 1 enrolled subjects aged ≥18 years with moderate or severe cfl at maximum smile • study 2 enrolled subjects aged 18–65 years with moderate or severe fhl at maximum eyebrow elevation only, or in conjunction with moderate or severe cfl at maximum smile, and moderate or severe gl at maximum frown • all subjects were fluent in english • key exclusion criteria: ─ prior periorbital surgery, facial or brow lift, or related procedure, or midfacial or periorbital treatment with permanent soft-tissue fillers, polytetrafluorethylene (gore-tex) implantation, or autologous fat transplantation ─ nonablative resurfacing laser/light treatment, microdermabrasion, or superficial peels within 3 months ─ cosmetic procedure with medium depth to deep facial chemical peels, midfacial or periorbital laser skin resurfacing, or permanent make-up within 6 months ─ midfacial or periorbital treatment with non-permanent soft-tissue filler within the previous 12 months ─ botulinum toxin treatment within 6 months figure 1. study designs study 1 study 2 concept elicitation interview: open-ended questions about psychological impacts of cfl subjects complete the flo-11 questionnaire targeted questions about relevancy of flo-11 items and flo-11 overall for assessing psychological impacts of cfl concept elicitation interview: open-ended questions about impacts of fhl (n=20) or ufl (n=20); subjects were also asked to define the psychological impacta targeted questions about relevancy of flo-11 items and flo-11 overall for assessing psychological impacts of fhl or ufl subjects aged ≥18 years with moderate or severe cfl at maximum contraction (n=41) subjects aged 18–65 years with moderate or severe fhl only (n=9) or with moderate or severe ufl (cfl, fhl, and gl) at maximum contraction (n=20) aeleven subjects in addition to the 9 subjects with fhl only completed interviews about the impact of fhl. cfl, crow’s feet lines; fhl, forehead lines; gl, glabellar lines; ufl, upper facial lines. interview conduct • both studies included a concept elicitation (ce) phase, followed by targeted questions about the relevancy of the flo-11 questionnaire. all interviews were audio or video recorded, with each subject’s permission • in the ce phase, subjects were asked open-ended questions by trained interviewers about the psychological impacts of their particular facial wrinkles: cfl in study 1, and fhl or ufl combined (ie, cfl, fhl, and gl) in study 2 ─ probing questions were asked, if necessary, to elicit concepts related to the psychological impact of their particular facial wrinkles • following the ce phase, subjects were asked to complete the flo-11 questionnaire and provide feedback on the relevancy of each item to the psychological impact of their particular facial wrinkles analysis • interview transcripts were imported into atlas.ti version 7.0 (atlas.ti gmbh; berlin, germany) to facilitate the organization and analyses of qualitative data. transcripts were analyzed on an ongoing basis, using a grounded theory approach to produce rich descriptions and theoretical explanations for the topic • codes consisting of root concepts elicited from the subjects and related to the research questions were linked to relevant portions of the transcript texts. each coded transcript was reviewed by ≥2 members of the project team until a consensus was reached • at the end of the coding process, the project team evaluated patterns in the data, with interpretation performed using a constant comparison method results subjects • study 1 enrolled 41 subjects with moderate or severe cfl (cfl cohort) • study 2 included 29 subjects; 9 had moderate or severe fhl only and 20 had moderate or severe cfl, fhl, and gl (ufl cohort) ─ in the latter group, 11 subjects in addition to the 9 with fhl only completed interviews about their fhl (fhl cohort) • study participants ranged in age from 24–72 years, and most were female and white (table 1) table 1. demographics and baseline characteristics characteristic study 1 study 2 cfl cohort (n=41) fhl cohort (n=20) ufl cohort (n=20) age, years, mean (sd) 50.7 (20.8) 44.7 (15.6) 50.4 (13.8) age, years, range 25–69 24–72 24–72 female, n (%) 36 (87.8) 14 (70.0) 14 (70.0) white, n (%) 34 (82.9) 17 (85.0) 17 (85.0) cfl severity at maximum smile, n (%) moderate 28 (68.3)a — 11 (55.0) severe 11 (26.8) — 9 (45.0) fhl severity at maximum eyebrow elevation, n (%) moderate — 8 (40.0) 7 (35.0) severe — 12 (60.0) 13 (65.0) gl severity at maximum frown, n (%) moderate — — 10 (50.0) severe — — 10 (50.0) adata shown for left side. corresponding data for right side: 29 (70.7%) with moderate and 10 (24.4%) with severe cfl. cfl, crow’s feet lines; fhl, forehead lines; gl, glabellar lines; sd, standard deviation; ufl, upper facial lines. concept elicitation phase interview study 1 • the most common appearance and behavioral impacts of cfl are shown in figure 2a • the most common psychological impacts of cfl were looking older than desired, feeling depressed/sad, feeling older, and looking less attractive (figure 2b) figure 2. the most commonly reported (≥20% of subjects) appearance, emotional, and physical impacts (a) and psychological impacts (b) of crow’s feet lines in study 1 20 24 32 37 42 0 5 10 15 20 25 30 35 40 45 50 feeling less confident looking less attractive feeling older feeling depressed/sad looking older than desired subjects (%) cfl cohort 37 34 44 46 73 32 51 61 63 68 83 85 85 0 10 20 30 40 50 60 70 80 90 100 using creams physical impacts feeling bad about appearance feeling less attractive feeling bothered feeling older emotional impacts looking older than actual age looking stressed looking not well rested looking less attractive looking tired looking older than desired looking older skin appears not smooth appearance impacts subjects (%) cfl cohort b. interview question: do you think your cfl have any psychological impact on yourself? if yes, how so? a. if necessary, the following probes were asked: what does psychological impact mean to you? what feelings or emotions would you consider are psychological impacts due to cfl? would you consider any cfl impacts already discussed to be a psychological impact? study 2 • the most common appearance and behavioral impacts of fhl and ufl are shown in figures 3a and 3b, respectively • the most common psychological impacts of fhl were feeling bothered, feeling self-conscious, feeling older, and feeling less confident (figure 4a) • for the ufl cohort, the most common psychological impacts were feeling bothered, feeling older, feeling less confident, and feeling less attractive (figure 4b) figure 3: the most commonly reported (≥20% of subjects) appearance and emotional impacts of forehead lines (a) and upper facial lines (b) in study 2 20 25 30 35 45 20 25 30 35 35 50 50 75 85 feeling less attractive feeling less confident feeling older feeling self-conscious feeling bothered emotional impacts looking not well rested looking stressed skin appears less smooth looking older than actual age looking tired looking angry looking less attractive looking older than desired looking older overall appearance impacts fhl cohort subjects (%) 0 10 20 30 40 50 60 70 80 90 100 25 30 30 40 40 20 25 30 40 50 50 65 70 0 10 20 30 40 50 60 70 80 90 100 feeling good/bad about appearance feeling less attractive feeling less confident feeling bothered feeling older emotional impacts looking older than actual age looking not well rested looking angry looking tired looking stressed looking less attractive looking older than desired looking older overall appearance impacts ufl cohort subjects (%) b. a. fhl, forehead lines; ufl, upper facial lines. figure 4. the most commonly reported (≥20% of subjects) psychological impacts of forehead lines (a) and upper facial lines (b) in study 2 20 25 30 35 45 0 5 10 15 20 25 30 35 40 45 50 feeling less attractive feeling less confident feeling older feeling self-conscious feeling bothered subjects (%) fhl cohort 25 30 30 40 40 0 5 10 15 20 25 30 35 40 45 50 feeling good/bad about appearance feeling less attractive feeling less confident feeling older feeling bothered subjects (%) ufl cohort b. a. fhl, forehead lines; ufl, upper facial lines. flo-11 questionnaire • several items of the flo-11 questionnaire were frequently reported to be adequate measures of the psychological impact of cfl, fhl, and ufl overall. for example, items 1, 3, and 5 elicited >68% response across all cohorts (table 2) table 2. flo-11 items reported as psychological impacts of upper facial lines interview question: do you think that this questionnaire asks you questions about the psychological impacts of cfl? if so, which questions ask you about the psychological impacts of cfl? flo-11 item, n (%) study 1 study 2 cfl cohort (n=41) fhl cohort (n=20) ufl cohort (n=20) item 1: feeling bothered 28 (68) 16 (80) 14 (70) item 2: looking older than desired 29 (71) 14 (70) 11 (55) item 3: feeling less attractive 32 (78) 17 (85) 16 (80) item 4: looking older than my actual age 19 (46) 15 (75) 13 (65) item 5: looking less attractive 31 (76) 17 (85) 14 (70) item 6: looking not well rested 17 (42) 11 (55) 10 (50) item 7: skin appears less smooth 15 (37) 12 (60) 10 (50) item 8: looking tired 19 (46) 13 (65) 13 (65) item 9: looking stressed 22 (54) 14 (70) 14 (70) item 10: looking angry 20 (49) 13 (65) 11 (55) item 11: feeling good about appearance 23 (56) 16 (80) 14 (70) cfl, crow’s feet lines; fhl, forehead lines; ufl, upper facial lines. • the flo-11 items most frequently reported ─ cfl cohort: item 3 (feeling unattractive; 78.0%) and item 2 (feeling older than desired; 70.7%) ─ fhl cohort: item 3 (85.0%) and item 5 (feeling less attractive than desired; 85.0%) ─ ufl cohort: items 3 (feeling unattractive; 80.0%) and 1 (bothered by lines), 5 (looking less attractive than desired), 9 (looking stressed), and 11 (feeling good/bad about appearance) (each 70.0%) • the majority of subjects in each cohort reported that the flo-11 questionnaire is a comprehensive measure of the psychological impacts of their particular facial lines (figure 5) figure 5. subjects reporting that the flo-11 questionnaire is a comprehensive measure of psychological impacts of crow’s feet lines, forehead lines, and upper facial lines 0 10 20 30 40 50 60 70 80 90 100 cfl fhl ufl n=41 n=20 n=20 73 65 60 s ub je ct s (% ) cfl, crow’s feet lines; fhl, forehead lines; ufl, upper facial lines. conclusions • cfl, fhl, and ufl are associated with multiple psychological impacts, including feeling older, less attractive, bothered, self-conscious, and less confident • these facial lines also affect self-perception, as subjects frequently reported looking older than their actual age, looking less attractive, and looking angry • more than 50% of subjects reported that 6 items, 9 items, and all 11 items on the flo-11 questionnaire assess the psychological impact of cfl, ufl, and fhl, respectively • the majority of subjects reported that the flo-11 is a comprehensive measure of the psychological impacts of their particular facial lines • based on these findings, the flo-11 is an appropriate and comprehensive measure of the psychological impact of cfl, fhl, and ufl overall from the subject’s perspective references 1. finn cj, et al. dermatol surg. 2003;29(5):450-5. 2. beer k, beer j. facial plast surg. 2009;25(5):281-4. 3. yaworsky a, et al. j cosmet dermatol. 2014;13(4):297-306. 4. cox se, finn jc. int ophthalmol clin. 2005;45(3):13-24. 5. gupta ma, gilchrest ba. dermatol clin. 2005;23(4):643-8. acknowledgments this study was sponsored by allergan plc, dublin, ireland. medical writing and editorial assistance was provided to the authors by cactus communications and was funded by allergan plc. all authors met the icmje authorship criteria. neither honoraria nor other form of payments were made for authorship. financial disclosures s dayan is an employee of denova research, which received remuneration for this research from allergan plc. sg yoelin serves as an investigator and on a speakers’ bureau for allergan plc. k de boulle serves as a consultant and investigator and on a speakers’ bureau for allergan plc. il ferrusi was an employee of allergan plc at the time of this research. to obtain a pdf of this poster and to view a video on the mechanism of action of botox: scan the qr code or visit www.allergancongressposters.com/359344 password botoxmoa123 charges may apply. no personal information is stored. enter a valid e-mail to send this qr code or click to download. please ensure that qrcode@allergancongressposters.com has been added to your safe senders list or spam filter. fall clinical dermatology conference, las vegas, october 12-15, 2017 fc17posterallergandayanpsychologicalimpactshorizontalfrontalislines.pdf presented at fall clinical dermatology conference 2019 | las vegas, nv, usa | 17–20 october, 2019 previously presented at 28th eadv congress 2019 background • plaque psoriasis (pso) is an inflammatory disease that affects around 3% of adults in the united states.1,2 • treatment options for pso include phototherapy/ photochemotherapy, topical treatments, systemic agents and biologics.3,4,5,6 • given the chronic nature of pso, sustained treatment efficacy over the long-term is highly important. however, loss of response over time has previously been associated with biologics in pso.7 • certolizumab pegol (czp) is an fc-free, pegylated, anti-tumor necrosis factor (tnf) which has led to durable clinical improvements in patients with pso over two years of treatment.8,9 • here, we report the clinical responses of pso patients over three years of czp treatment, using data from the cimpasi-1 (nct02326298) and cimpasi-2 (nct02326272) phase 3 trials. methods study design • data were pooled for patients enrolled in two phase 3 trials, cimpasi-1 (nct02326298) and cimpasi-2 (nct02326272) (figure 1). • this analysis includes all patients who were randomized to czp 400 mg every two weeks (q2w) or czp 200 mg q2w at week 0 (intent-to-treat population). • on entry to the open-label phase, all patients were initially treated with czp 200 mg q2w; subsequent dosing adjustment based on psoriasis area severity index (pasi) response was either mandatory or at the discretion of the investigator (figure 1). patients • ≥18 years of age with moderate to severe pso ≥6 months with pasi ≥12, ≥10% body surface area (bsa) affected, and physician’s global assessment (pga) ≥3 on a 5-point scale. • candidates for systemic pso therapy, phototherapy and/or photochemotherapy. • exclusion criteria: previous treatment with czp or >2 biologics; history of primary failure to any biologic or secondary failure to >1 biologic; erythrodermic, guttate or generalized pso types; current or history of chronic or recurrent viral, bacterial or fungal infections. study assessments and statistical analyses • patients were assessed through weeks 0–144 for: – pasi 75 (≥75% improvement from baseline) – pasi 90 (≥90% improvement from baseline) – dlqi 0/1 (dermatology life quality index score of 0/1 [remission]) • estimates of responder rate reflect the simple average response across the multiply imputed data sets, with missing data imputed using markov chain monte carlo (mcmc) methodology. results patient population • at week 0, 175 patients were randomized to czp 400 mg q2w and 186 patients to czp 200 mg q2w. • baseline characteristics were balanced across treatment groups (table 1). clinical response to week 144 • initial week 16 responder rates were durable through to week 48 for both czp 400 mg q2w and czp 200 mg q2w (figure 2). • in patients initially randomized to czp 200 mg q2w, pasi 75, pasi 90 and dlqi 0/1 responder rates were sustained for a further two years to week 144 (figure 2). • in patients initially randomized to czp 400 mg q2w, clinical response gradually declined following dose reduction to czp 200 mg q2w at week 48 (figure 2). conclusions • in patients randomized to czp 400 mg q2w, responder rates increased to week 48 and were higher than in the czp 200 mg q2w group. these rates then gradually decreased following dose reduction, indicating that continued treatment at 400 mg q2w may be needed to maintain optimal response. • long-term efficacy over three years was durable in patients who received czp 200 mg q2w. objective • to present pooled, three-year efficacy data from two phase three trials of certolizumab pegol in moderate to severe plaque psoriasis. certolizumab pegol for treatment of plaque psoriasis: pooled three-year efficacy outcomes from two phase 3 trials (cimpasi-1 and cimpasi-2) k. gordon,1 r. b. warren,2 a. b. gottlieb,3 a. blauvelt,4 d. thaçi,5 c. leonardi,6 y. poulin,7 m. boehnlein,8 s. kavanagh,9 c. arendt,10 k. reich11 1department of dermatology, medical college of wisconsin, milwaukee, wi, usa; 2dermatology centre, salford royal nhs foundation trust, manchester nihr biomedical research centre, the university of manchester, uk; 3department of dermatology, icahn school of medicine at mount sinai, new york, ny, usa; 4oregon medical research center, portland, or, usa; 5institute and comprehensive center for inflammation medicine, university hospital of lübeck, lübeck, germany; 6central dermatology and saint louis university school of medicine, st louis, mo, usa; 7centre de recherche dermatologique du québec métropolitain, québec, canada; 8ucb pharma, monheim, germany; 9ucb pharma, raleigh, nc, usa; 10ucb pharma, brussels, belgium; 11translational research in inflammatory skin diseases, institute for health services research in dermatology and nursing, university medical center hamburg-eppendorf, germany; skinflammation® center, hamburg, dermatologikum berlin, berlin, germany table 1. demographics and baseline characteristics for all patients randomized to czp 400 mg q2w and czp 200 mg q2w figure 1. pooled data from cimpasi-1 and cimpasi-2 apatients with exposure to ≥2 biologics (including anti-tnfs) for pso or psa prior to baseline, or primary failure to ≥1 (or secondary failure to ≥2) biologic therapies, were excluded from the study. bsa: body surface area; bmi: body mass index; dlqi: dermatology life quality index; pasi: psoriasis area severity index; pga: physician’s global assessment; pso: psoriasis; sd: standard deviation; tnf: tumor necrosis factor. aloading dose of czp 400 mg q2w at weeks 0, 2 and 4 or weeks 16, 18 and 20; bdepending on pasi response, any dose adjustments during the open-label period were either mandatory or at the discretion of the investigator. czp: certolizumab pegol; ld: loading dose; pasi: psoriasis area severity index; pga: physician’s global assessment; q2w: every two weeks. czp 400 mg q2w (n=175) czp 200 mg q2w (n=186) all czp (n=361) age, years, mean (sd) 45.0 (12.9) 45.6 (13.2) 45.3 (13.0) male, n (%) 103 (58.9) 125 (67.2) 228 (63.2) bmi, kg/m2, mean (sd) 31.2 (7.9) 32.0 (7.8) 31.6 (7.8) pso disease duration, years, mean (sd) 18.5 (12.6) 17.7 (12.9) 18.1 (12.7) prior anti-tnf therapy,a n (%) 39 (22.3) 44 (23.7) 83 (23.0) bsa affected, %, mean (sd) 23.6 (14.3) 23.5 (14.9) 23.5 (14.6) pasi, mean (sd) 19.6 (7.3) 19.2 (7.2) 19.4 (7.3) pga score, n (%) 3 (moderate) 126 (72.0) 128 (68.8) 254 (70.4) 4 (severe) 49 (28.0) 58 (31.2) 107 (29.6) dlqi total score, mean (sd) 13.7 (6.9) 14.2 (7.4) 14.0 (7.1) references 1. kurd sk. et al. j am acad dermatol 2009;60:218–24; 2. rachakonda td. et al. j am acad dermatol 2014;70:512–6; 3. elmets ca. et al. j am acad dermatol 2019; 4. menter a. et al. j am acad dermatol 2009;60:643–59; 5. menter a. et al. j am acad dermatol 2009; 61:451–85; 6. menter a. et al. j am acad dermatol 2019;80:1029–72; 7. levin ec. et al. j dermatol treat 2014;25:78–82; 8. gottlieb ab. et al. j am acad dermatol 2018;79:302–14; 9. gordon k. et al. aad 2019. author contributions substantial contributions to study conception/design, or acquisition/analysis/interpretation of data: kg, rbw, abg, ab, dt, cl, yp, mb, sk, ca, kr; drafting of the publication, or revising it critically for important intellectual content: kg, rbw, abg, ab, dt, cl, yp, mb, sk, ca, kr; final approval of the publication: kg, rbw, abg, ab, dt, cl, yp, mb, sk, ca, kr. author disclosures kg: honoraria and or research support from: abbvie, almirall, amgen, boehringer ingelheim, bristolmyers squibb, celgene, dermira inc., eli lilly, janssen, novartis, pfizer, sun pharma, and ucb pharma; rbw: grants and/or honoraria from abbvie, almirall, amgen, boehringer ingelheim, celgene, janssen, eli lilly, leo pharma, novartis, pfizer, sanofi, ucb pharma, xenoport; abg: research/educational grants: janssen, incyte, eli lilly, novartis, allergan and leo pharma. current consulting/advisory board agreements/speakers bureau: janssen; celgene, bristol-myers squibb, beiersdorf, abbvie, ucb pharma, novartis, incyte, eli lilly, dr. reddy's laboratories, valeant, dermira inc., allergan, sun pharma, sienna pharma; ab: consulting honoraria and clinical investigator: abbvie; aclaris; almirall; amgen; boehringer ingelheim; celgene; dermavant; dermira inc.; eli lilly; genentech/roche; gsk; janssen; leo pharma; meiji; merck; novartis; pfizer; purdue pharma, regeneron, sandoz, sanofi genzyme, sienna pharma, sun pharma, ucb pharma, valeant, vidac. speaker’s fees: eli lilly, janssen, regeneron, sanofi genzyme; dt: research grants from celgene and novartis; honoraria for participation on ad boards, and speaker/ consultancy fees for abbvie, almiral, amgen, boehringer ingelheim, celgene, dignity, dr. reddy's laboratories, galapagos, gsk, janssen, leo, morphosis, msd, eli lilly, novartis, pfizer, sandoz-hexal, pfizer, regeneron/sanofi, ucb pharma; cl: speaker (honoraria) for abbvie; celgene; novartis; eli lilly. investigator for actavis; abbvie; amgen; boehringer ingelheim; celgene; coherus; corrona; dermira inc; eli lilly; galderma; glenmark; janssen; leo pharma; merck; novartis; novella; pfizer; sandoz; stiefel; wyeth. consulting and advisory board honoraria for abbvie; amgen; boehringer ingelheim; dermira inc.; eli lilly; janssen; leo pharma; pfizer; sandoz; ucb pharma; vitae; yp: speaker (honoraria) from: abbvie; celgene; janssen; eli lilly; leo pharma; novartis; regeneron sanofi genzyme. investigator (research grants) from abbvie; baxter; boehringer ingelheim pharma; celgene; centocor/janssen; eli lilly; emd serono; gsk; leo pharma; medimmune; merck; novartis; pfizer; regeneron; takeda; ucb pharma; mb, ca: employees of ucb pharma; sk: employee of ucb pharma; consulting fees from avexis, colorado prevention center, diamedica, puretech, ucb pharma, zosano; kr: advisor and/or paid speaker for and/or participated in clinical trials sponsored by: abbvie, affibody, amgen, biogen, boehringer ingelheim, celgene, centocor, covagen, forward pharma, gsk, janssen-cilag, kyowa kirin, leo pharma, eli lilly, medac, merck sharp & dohme, novartis, ocean pharma, pfizer, regeneron, samsung biopepis, sanofi, takeda, ucb pharma, valeant, xenoport. acknowledgements the studies were funded by dermira inc. in collaboration with ucb pharma. ucb is the regulatory sponsor of certolizumab pegol in psoriasis. we thank the patients and their caregivers in addition to the investigators and their teams who contributed to this study. the authors acknowledge bartosz łukowski, msc, ucb pharma, brussels for publication coordination and amelia frizell-armitage, costello medical, cambridge, uk for medical writing and editorial assistance. all costs associated with development of this poster were funded by ucb pharma. figure 2. clinical response over three years of treatment (144 weeks) estimates of responder rate reflect the simple average response across the multiply imputed data sets, with missing data imputed using markov chain monte carlo (mcmc) methodology. aall patients received czp 200 mg q2w at week 48; dose adjustments were permitted during the open-label phase based on pasi response and were either mandatory or at the discretion of the investigator; bpatients received loading dose of czp 400 mg at weeks 0, 2 and 4. czp: certolizumab pegol; dlqi 0/1: dermatology life quality index 0/1; mcmc: markov chain monte carlo; pasi 75/90: ≥75/90% improvement from baseline in psoriasis area and severity index. 80 60 40 20 100 0 0 48 72 96 120 144 week 24 open-label period with possible dose adjustmentaopen-label period with possible dose adjustmenta 0 0 r e sp o n d e r ra te ( % ) at week 48 all patients received czp 200 mg q2w at week 48 all patients received czp 200 mg q2w czp 400 mg q2w czp 200 mg q2wa (n=175) dose reduction czp 200 mg q2wb czp 200 mg q2wa (n=186) dose continuation 0 48 72 96 120 144 week 24 0 48 72 96 120 144 week 24 80 60 40 20 100 r e sp o n d e r ra te ( % ) 80 60 40 20 100 r e sp o n d e r ra te ( % ) at week 48 all patients received czp 200 mg q2w at week 48 all patients received czp 200 mg q2w at week 48 all patients received czp 200 mg q2w 71.071.0 65.665.6 45.445.4 42.042.0 45.645.6 40.840.8 68.568.5 80.980.9 49.049.0 60.160.1 45.045.0 55.355.3 open-label period with possible dose adjustmentaopen-label period with possible dose adjustmenta open-label period with possible dose adjustmentaopen-label period with possible dose adjustmenta a) pasi 75 b) pasi 90 c) dlqi 0/1 0 16 32 40 48 144 maintenance periodinitial treatment period (double blind) open-label treatment <pasi 50 withdrawn screening 1:2:2 week lda czp 200 mg q2w (n=186) czp 200 mg q2w czp 400 mg q2w randomization ≥pasi 50 ≥pasi 50 ≥pasi 50 96 open-label dose switchingb <pasi 50 withdrawn placebo q2w ≥pasi 75 responders <pasi 50 withdrawn <pasi 50 entered escape arm (czp 400 mg q2w) czp 400 mg q2w (n=175) lda ≥pasi 50 <pasi 75 introduction ■ atopic dermatitis (ad) is a chronic, relapsing and remitting inflammatory skin disease, characterized by intense pruritus and eczematous lesions. ad can substantially impact patients’ sleep and quality of life1–4 ■ there is a need for efficacious, non-steroidal topical therapies for ad, without restrictions relating to duration, extent of use, and application sites ■ tapinarof (vtama®; dermavant sciences, inc., usa) is a first-in-class, non-steroidal, topical aryl hydrocarbon receptor (ahr) agonist approved by the food and drug administration for the treatment of plaque psoriasis in adults, and under investigation for the treatment of plaque psoriasis in children down to 2 years of age and for ad in adults and children down to 2 years of age5 ■ tapinarof cream 1% once daily (qd) demonstrated significant efficacy versus vehicle and was well tolerated in adults with mild to severe plaque psoriasis in two identical, 12-week, phase 3 trials, psoaring 1 (nct03956355) and psoaring 2 (nct03983980)6 – efficacy continued to improve beyond the 12-week trials in psoaring 3 (nct04053387), the long-term extension trial7 ■ tapinarof specifically binds to and activates the ahr, a ligand-dependent transcription factor. this leads to downregulation of inflammatory th2 cytokines (including interleukin [il]-4, il-5, and il-13), increase in expression of skin barrier proteins related to keratinocyte differentiation (including filaggrin, loricrin, and involucrin), and antioxidant activity8–12 (figure 1) figure 1. potential mechanisms of action of tapinarof in atopic dermatitis *demonstrated in vitro. †demonstrated in mouse models. ‡demonstrated ex vivo. ahr, aryl hydrocarbon receptor; arnt, aryl hydrocarbon receptor nuclear translocator; il, interleukin; nrf2, nuclear factor erythroid 2-related factor 2; ros, reactive oxygen species; tap, tapinarof. ■ tapinarof cream 1% qd demonstrated significant efficacy versus vehicle and was well tolerated in adults and adolescents with moderate to severe ad in a 12-week phase 2b trial (nct02564055)13,14 – efficacy was generally maintained through the last trial visit, 4 weeks after completing treatment13,14 ■ in a phase 1 pharmacokinetics (pk) evaluation of tapinarof cream 1% in adults (n=6) with moderate to severe ad, there were low levels of systemic absorption that decreased from baseline to day 21 of assessment (mean 1.2 ng [10–9]/ml [day 1] and 0.15 ng/ml [day 21])15 ■ tapinarof cream 1% has also been assessed in a 4-week, maximaluse pk trial in adults with extensive plaque psoriasis; tapinarof was well tolerated with limited systemic exposure, even in patients with up to 46% body surface area (bsa) affected16 objectives ■ to present the 4-week, maximal-use ad trial design and patient baseline characteristics ■ to assess the safety, tolerability, pk, and efficacy of tapinarof cream 1% qd in adolescents and children with extensive ad in the 4-week, maximal-use trial methods trial design ■ in this phase 2a, multicenter, open-label trial (nct05186805), adolescents and children with extensive ad will receive tapinarof cream 1% qd for 27 days (figure 2) ■ patients or caregivers will be instructed to apply a thin layer of tapinarof cream, sufficient to cover each lesion ■ tapinarof pk will be assessed at days 1 (baseline) and 28 – the screening blood sample will be used for baseline pre-dose pk assessment if the patient is enrolled ■ key inclusion and exclusion criteria are shown in table 1 ■ eligible patients completing this trial will have the option to enroll in an open-label, long-term extension trial (nct05142774) to receive up to an additional 48 weeks of tapinarof treatment figure 2. maximal-use pk trial design in adolescents and children with ad ad, atopic dermatitis; pk, pharmacokinetics; qd, once daily. table 1. key inclusion and exclusion criteria inclusion criteria exclusion criteria males and females aged 2–17 years significant dermatologic or inflammatory condition and concurrent skin lesions in the treatment area or pruritus due to conditions other than ad a clinical diagnosis of ad by hanifin and rajka criteria17 patients who would not be considered suitable for topical therapy %bsa involvement ≥25% for adolescents (12–17 years) or ≥35% for children (2–11 years) use of any prohibited medication or procedure within the indicated period before the baseline visit a viga-adtm score of ≥3 at screening and baseline (pre-dosing) history of sensitivity to the trial medications ad present for ≥6 months for patients aged 6–17 years or 3 months for patients aged 2–5 years previous known participation in a clinical trial with tapinarof ad, atopic dermatitis; bsa, body surface area; viga-adtm, validated investigator global assessment for atopic dermatitistm. primary endpoints ■ incidence, frequency, and nature of adverse events (aes) and serious aes ■ change from baseline in laboratory values and vital signs ■ mean investigator-assessed local tolerability scale scores by visit (overall and sensitive areas) ■ tapinarof plasma pk parameters on day 1, including: – area under the plasma concentration versus time curve from baseline to the last quantifiable concentration (auc 0–last ) – maximum plasma concentration (c max ) – time to maximum plasma concentration (t max ) – time of last quantifiable concentration (t last ) ■ tapinarof plasma concentration on day 28 secondary endpoints ■ change in validated investigator global assessment for atopic dermatitistm (viga-adtm) score by visit ■ proportion of patients with a viga-adtm score of clear (0) or almost clear (1) by visit ■ proportion of patients with ≥50%, ≥75%, and ≥90% improvement in eczema area and severity index (easi) score by visit ■ mean change and percent change in easi score by visit ■ mean change and percent change in %bsa affected by visit ■ proportion of patients with a baseline peak pruritus-numeric rating scale (pp-nrs) score of ≥4 who achieve a ≥4-point reduction in pp-nrs score by visit – proportion of patients ≥12 years old with a baseline pp-nrs score ≥4 who achieve a ≥4-point reduction in pp-nrs score by visit – proportion of patients 2–12 years old with a baseline pp-nrs score ≥4 who achieve a ≥4-point reduction in pp-nrs score by visit – mean change in pp-nrs score at each visit by age group statistical analyses ■ safety analyses will include all patients who received at least one application of tapinarof ■ analyses of efficacy endpoints will be based upon the safety population results baseline patient demographics and disease characteristics ■ overall, 36 patients were enrolled at nine sites in the us and canada ■ patients’ baseline demographics and disease characteristics are shown in table 2 – equal proportions of patients (33.3% [12/36]) were young children (2–6 years), children (7–11 years), and adolescents (12–17 years) – most patients (77.8%) across the three groups had a viga-adtm score of 3 (moderate) – overall mean (standard deviation [sd]) easi score was 23.8 (9.2), with a range of 8.2–49.6 indicating moderate to severe ad – overall mean (sd) %bsa affected was 42.8% (15.1%), with a range of 26%–90% table 2. baseline demographics and disease characteristics tapinarof cream 1% qd young children 2–6 years (n=12) children 7–11 years (n=12) adolescents 12–17 years (n=12) overall (n=36) age, years, mean (sd) 3.7 (1.4) 8.2 (1.4) 14.8 (1.8) 8.9 (4.9) male, n (%) 9 (75.0) 7 (58.3) 8 (66.7) 24 (66.7) viga-adtm of 3 (moderate), n (%) 8 (66.7) 9 (75.0) 11 (91.7) 28 (77.8) viga-adtm of 4 (severe), n (%) 4 (33.3) 3 (25.0) 1 (8.3) 8 (22.2) easi, mean (sd) 30.2 (8.6) 21.0 (10.0) 20.3 (5.5) 23.8 (9.2) bsa affected, %, mean (sd) 52.4 (19.1) 42.0 (10.0) 33.9 (8.6) 42.8 (15.1) bsa, body surface area; easi, eczema area and severity index; qd, once daily; sd, standard deviation; viga-adtm, validated investigator global assessment for atopic dermatitistm. conclusions ■ in a phase 2b trial, tapinarof cream 1% qd demonstrated significant efficacy versus vehicle and was well tolerated in adolescents and adults with moderate to severe ad13,14 ■ tapinarof cream 1% has shown minimal systemic absorption in adults with ad or psoriasis, even with extensive bsa affected of up to 46%15,16 ■ this maximal-use pk trial will assess the safety, tolerability, pk, and efficacy of tapinarof cream 1% qd in 36 adolescents and children down to 2 years of age with extensive, moderate to severe ad ■ in addition, tapinarof cream 1% qd is being evaluated for the treatment of ad in adults and children down to 2 years of age in three phase 3 clinical trials (adoring 1 [nct05014568], adoring 2 [nct05032859], and adoring 3 [nct05142774]) references 1. weidinger s and novak n. lancet. 2016;387:1109–1122. 2. bieber t. n engl j med. 2008;358:1483– 1494. 3. carroll cl, et al. pediatr dermatol. 2005;22:192–199. 4. lewis-jones s. int j clin pract. 2006;60:984–992. 5. dermavant sciences. vtama (tapinarof) cream, 1%: us prescribing information. 2022. https://www.vtama.com/docs/dmvt_vtama_pi.pdf. accessed july 2022. 6. lebwohl m, et al. n engl j med. 2021;385:2219–2229. 7. strober b, et al. j am acad dermatol. 2022. https://doi.org/10.1016/j. jaad.2022.06.1171. 8. bissonnette r, et al. j am acad dermatol. 2021;84:1059–1067. 9. dermavant dof [dmvt-505 th2 polarization; apr 2015]. 10. dermavant dof [dmvt-505 ad mouse model; oct 2016]. 11. smith sh, et al. j invest dermatol. 2017;137:2110–2119. 12. kim be, et al. allergy asthma immunol res. 2018;10:207–215. 13. peppers j, et al. j am acad dermatol. 2019;80:89–98. 14. paller a, et al. j am acad dermatol. 2021;84:632–638. 15. bissonnette r, et al. clin pharmacol drug dev. 2018;7:524–531. 16. jett je, et al. am j clin dermatol. 2022;23:83–91. 17. hanifin jm and rajka g. acta dermatovener (stockholm) suppl. 1980;92:44–47. acknowledgments this trial was funded by dermavant sciences, inc. the authors thank the participating investigators, patients and their families, and colleagues involved in the conduct of the trial. a.p. is an investigator (without personal compensation) for abbvie, anaptysbio, dermavant sciences inc., eli lilly, incyte, janssen, krystal, regeneron, and ucb pharma, a consultant (with honoraria) for abbvie, acrotech, almirall, amgen, amryt, arcutis, arena, azitra, biocryst, biomx, boehringer ingelheim, botanix, bridgebio, castle biosciences, catawba, eli lilly, exicure, gilead, incyte, janssen, kamari, leo, novartis, pfizer, pierre fabre, rapt, regeneron, sanofi/genzyme, seanergy, ucb pharma, union, and on the data safety monitoring board for abbvie, abeona, bausch, bristol myers squibb, galderma, inmed, and novan. a.a.h. has received grants/honoraria/ research support from abbvie, almirall, arcutis, dermavant sciences inc., gsk (as part of a data safety monitoring board), incyte, leo pharma, mayne, novan, and verrica. j.e.j., p.m.b., d.s.r., and s.c.p. are employees of dermavant sciences, inc., with stock options. editorial and medical writing support under the guidance of the authors was provided by apothecom, uk, and was funded by dermavant sciences, inc. in accordance with good publication practice (gpp3) guidelines (ann intern med. 2015;163:461–464). contact dr paller at apaller@nm.org with questions or comments. open-label treatment (27 days) adolescents and children�with ad screening for up to 30 days tapinarof cream 1% qd follow-up visit ~7 days after end of treatment tapinarof cream 1% once daily for the treatment of extensive atopic dermatitis in adolescents and children: 4-week maximal-use trial amy paller,1 adelaide a. hebert,2 john e. jett,3 philip m. brown,3 david s. rubenstein,3 stephen c. piscitelli3 1northwestern university feinberg school of medicine, chicago, il, usa; 2mcgovern school of medicine and children’s memorial hermann hospital, uthealth mcgovern, houston, tx, usa; 3dermavant sciences, inc., morrisville, nc, usa patient tolerability of tazarotene foam, 0.1%, and impact on patient compliance real world patient perceptions of the use of calcipotriene foam 0.005% in the treatment of plaque psoriasis francisco kerdel, md, faad;a christina don pa, mcmsc;b renata block pa-c, mms; caitlin lewis, phd;c rhonda schreiber msrnd conclusions methods resultsintroduction participants were asked “how satisfied are you with the improvement in psoriasis you’ve seen in the areas you have treated with calcipotriene foam, 0.005%?”. the responses from the final survey, after 8 weeks on therapy, are shown in the chart to the left. • patient satisfaction levels are strong across both genders and all ages with no significant difference in any one group. • satisfaction in the severity of psoriasis cohort increases as the bsa affected increases. • patients who treated their scalp only were most satisfied (85%), followed by those treating both the body and scalp (78%), and then body alone (70%). • patients who used the product as a monotherapy were more satisfied (79%) than those who used it in combination with other therapies (72%). affiliations and disclaimersreferences 1. gupta r, debbaneh mg, liao w, genetic epidemiology of psoriasis,. curr dermatol rep. 2014 march; 3(1):61-78. 2. stern rs, nijsten t, feldman sr, margolis dj, rolstad t. psoriasis is common, carries a substantial burden even when not extensive, and is associated with widespread treatment dissatisfaction. j investig dermatol symp proc. 2004 mar;9(2):136-9. 3. tan x, feldman sr, chang j, balkrishnan r. topical drug delivery systems in dermatology: a review of patient adherence issues. expert opin drug deliv. 2012 oct;9(10):1263-71. 4. stein gold lf. topical therapies for psoriasis: improving management strategies and patient adherence. semin cutan med surg. 2016 mar;35(2 suppl 2):s36-44; quiz s45. 5. del rosso jq, kircik lh, zeichner j, stein gold l. the clinical relevance and therapeutic benefit of established active ingredients incorporated into advanced foam vehicles: vehicle characteristics can influence and improve patient outcomes j drugs dermatol. 2019 feb 1;18(2s):s100-s107. 6. eastman wj, malahias s, delconte j, dibenedetti d. assessing attributes of topical vehicles for the treatment of acne, atopic dermatitis, and plaque psoriasis. cutis. 2014 jul;94(1):46-53. 7. feldman , s. r., mills, m., brundage, t., & eastman, w. j. (2013, march). a multicenter, randomized, double-blind study of the efficacy and safety of calcipotriene foam, 0.005%, vs vehicle foam in the treatment of plaque-type psoriasis of the scalp. jdd, 12(3), 300-306. 8. data on file, mayne pharma, inc. participant demographics 37 37 37 36 37 44 30 36 32 40 40 32 46 37 39 34 39 39 38 45 37 34 42 38 42 36 40 38 39 41 40 38 0 10 20 30 40 50 60 70 80 90 100 p e rc e n t o f r e sp o n d e n ts overall satisfaction at week 8 (n=276) very satisfied satisfied age severity of psoriasis location of use use of treatment 81% 74% 78% 72% 74% 74% 76% 80% 70% 85% 78% 79% 72% *% at the top of the bars = respondents who were either satisfied or very satisfied total respondents to week 8 survey n=276 n(%) gender male 102 (37) female 172 (62) other 2 (1) age 18-30 55 (20) 31-40 67 (24) 41-50 62 (22) 51-60 50 (18) 61+ 42 (15) race caucasian 221 (80) african american 14 (5) hispanic/latino 19(7) asian 11 (4) other 11 (4) severity of psoriasis %bsa less than 3% 110 (40) between 3-10% 121 (44) more than 11% 45 (16) location of treatment body only 134 (49) scalp only 71 (26) body and scalp 71 (26) use of treatment used alone 162 (59) used in combination 114 (41) gender • participants were asked “has your itch improved since starting calcipotriene foam, 0.005%? if yes, how improved?” • at week 8, 71% of participants reported an improvement in itch • 60% reported moderate or strong improvement. 29% 37% 23% 11% 71% perceived improvement in itch at week 8 (n=276) very improved moderately improved slightly improved 26 57 65 61 59 70 57 59 42 28 25 29 30 25 33 30 25 12 7 7 8 5 8 9 0 20 40 60 80 100 p e rc e n t o f r e sp o n d e n ts product attribute rating (n=276) excellent good fair 68% 85% 80% 91% 89% 95% 90% 89% *% at the top of the bars = sum of excellent and good yesno discussion 62 11 12 7 8 0 10 20 30 40 50 60 70 foam solution cream lotion ointment p e rc e n t o f r e sp o n d e n ts preferred treatment formulation (n=276) patients were invited to upload photographic evidence to illustrate their treatment progress over the 8 week period. this patient, a caucasian male, aged 62, was using calcipotriene foam, 0.005% on his body only, as a monotherapy. the reduction in visible plaque is clearly apparent. this patient was “very satisfied” at weeks 4 and 8. registration week 2 week 4 week 8 psoriasis is a common chronic immune-mediated inflammatory disease of the skin, with approximately 150,000 newly diagnosed patients in the united states each year.1 most patients report their disease has significant physical and psychosocial impact on their lives and non-adherence to topical psoriasis treatment has been correlated to patient perception of vehicle attributes and negative treatment outcomes.2-6 calcipotriene foam, 0.005% is the only steroid-free vitamin d3 analog approved for use in a foam vehicle and has proven safety and efficacy as a monotherapy.7 patient questionnaires administered during the calcipotriene foam, 0.005%, phase iii trials reported positive patient perceptions of the foam vehicle and therapeutic outcomes in psoriasis. these positive results in a controlled setting prompted a series of surveys to current users of calcipotriene foam, 0.005% to gather patient perspectives on its use in “real world” clinical practice. • a total of 276 participants completed the final survey at week 8 with diversity across gender, age, race, and severity of psoriasis. • the severity of patients’ psoriasis was described as % of body surface area (%bsa), where less than 3% can be considered mild, 3-10% moderate, and >11% as severe. • participants were also asked which areas of their body they were treating and whether they were using the product alone or in combination with other treatments. • participants were asked to rate a number of attributes of calcipotriene foam 0.005% in the 8 week survey and rated all very strongly. • when asked to rank the different topical formulations in order of preference, foam was clearly the most preferred option with 62% of participants ranking it number one. • the next most preferred formulation was cream (12%), then solution (11%). methods the completed surveys represent a significant sample size with diversity across gender, race and age. the foam formulation was preferred by the majority of participants, who rated all vehicle attributes very highly. patients perceived the treatment as effective and submitted photographic evidence to support this. overall calcipotriene foam, 0.005% was rated by patients as an effective and easy to use topical treatment for psoriasis. the results of these surveys support the phase iii clinical trial questionnaire results and point to a high likelihood for compliance with treatment regimens which include calcipotriene foam, 0.005%. 276 patients completed the final survey at week 8, with 76% either satisfied or very satisfied with the improvement in psoriasis they saw with the product. at week 8 the highest satisfaction rates were reported by the following subsets: those using calcipotriene foam, 0.005% on their scalp alone (85%), those with severe psoriasis (>11% bsa) (80%), and those using using the product as monotherapy (79%). satisfaction did not differ significantly by gender (76% for males and 75% for females) and no trend was seen across age groups (between 72-81%). additionally, after using the foam for 8 weeks, 73% of participants indicated they were likely or very likely to continue use of the product, and 79% indicated they would be likely or very likely to recommend the product to a friend or family member.8 all vehicle attributes rated highly and patients showed a very strong preference for the foam vehicle in comparison to other formulations. 76% 76% 75% a. dermatology residency program at the lecomt/larkin community hospital, palm springs campus, hialeah, florida; florida academic dermatology center, coral gables, florida; florida international university, miami, florida. b. florida academic dermatology center, coral gables, florida; c. clewy communications, raleigh, nc; d. mayne pharma, greenville, nc. these surveys and analysis were supported by mayne pharma. • patients with plaque psoriasis who were being treated with calcipotriene foam, 0.005%, were asked to rate their experiences using the product over the course of 8 weeks. • surveys were administered at registration and then weeks 2, 4 and 8 to gather feedback on patient satisfaction with the product, perceived improvement in symptoms and itch, vehicle attributes, and topical vehicle preference. • patients completed surveys within 3 days to ensure feedback was gathered at the specific time points. • patients were also invited to submit photographs to show their treatment progress. materials & methods (continued) ada exposure • “overall exposure to ada” (outside of and within the registry) was calculated as time from the initial (first ever) ada dose to 14 days after the last ada dose in the registry, excluding the total number of days of treatment interruption in the registry. • “registry exposure to ada” (within the registry) was calculated as time from first ada dose in the registry to 14 days after the last ada dose in registry, excluding the total number of days of treatment interruption in the registry. • a treatment interruption (ti) is defined as >70 days without any ada dose; ti starts at day 71 after ada was stopped. safety • all treatment-emergent aes (all-teaes) were events occurring from the date of initial (first ever) ada dose through 70 days after the date of the last ada dose in the registry, excluding aes occurring during tis. this included aes collected in the registry, collected retroactively before registry entry, and from feeder studies for patients rolling over from preregistry feeder clinical trials. • incidence rates for all-teaes are reported as events per 100 patient-years (e/100py) of overall exposure to ada. • standardized mortality ratio (smr): – smr was calculated as the ratio of observed to expected treatmentemergent deaths using the 2006 country-specific world health organization mortality rates. – an smr <1.0 indicates that the observed number of deaths is lower than the expected rate in an age-, sex-, and country-matched general population. effectiveness • the proportion of patients achieving physician global assessment (pga) score of “clear” or “minimal” were analyzed as observed during registry participation (patients were not necessarily receiving ada at the time of assessment). results • this 8-year interim analysis used data collected from 6045 patients (2554 new-rx patients, 42.2%) who were enrolled and dosed between 26 september 2008 and 30 november 2016 (table 1). • the majority of patients in esprit were from sites in the united states (69.5%) and canada (13.9%). table 1. patient demographics and disease characteristics at registry entry (all-rx and new-rx patient populations) demographic or characteristic all-rx n=6045 new-rx n=2554 sex male, n (%) 3485 (57.7) 1376 (53.9) female, n (%) 2560 (42.3) 1178 (46.1) racea, n (%)* white 5268 (87.3) 2221 (87.0) black 178 (2.9) 65 (2.5) asian 259 (4.3) 106 (4.2) american indian/alaska native 16 (0.3) 7 (0.3) native hawaiian or other pacific islander 40 (0.7) 25 (1.0) other 251 (4.2) 116 (4.5) multi-race 22 (0.4) 12 (0.5) age, y, median (range) 47 (18–94) 46 (18–91) weight, kg, median (range)* 87.0 (41.0–252.0)b 86.0 (41.0–218.0)c bmi, kg/m2, median (range) 29.4 (16.0–76.8)d 29.4 (16.0–69.9)e psoriatic arthritis, n (%)* not analyzedf 868 (34.1)g family history of psoriasis, n (%)* not analyzedf 1067 (41.9)h duration of psoriasisi, y, median (range) not analyzedf 13.4 (0–68.0)h pgaj, n (%)* clear 733 (12.2) 53 (2.1) minimal 1176 (19.5) 140 (5.5) mild 1150 (19.2) 312 (12.3) moderate 1778 (29.5) 1117 (43.9) severe 973 (16.1) 748 (29.4) very severe 213 (3.5) 172 (6.8) *percentages calculated on non-missing values. amissing data: all-rx, n=11; new-rx, n=2. bn=5931; cn=2497; dn=5912; en=2492. fnot analyzed because not all data were captured in the registry database. gn=2549; hn=2547. icalculated at registry entry. jmany patients had received ada before entering the registry, demonstrated by the number of patients entering the registry with a pga score of “clear” or “minimal.” missing data: all-rx, n=22; new-rx, n=12. ada=adalimumab; all-rx=all-treated patient population; bmi=body mass index; new-rx=new prescription patient population; pga=physician global assessment. • 3662 (60.6%) all-rx and 1372 (53.7%) new-rx patients are continuing in the registry as of 30 november 2016. – of those, 2494 (41.3%) all-rx and 791 (31.0%) new-rx patients have not permanently discontinued ada. – of those, 1688 (27.9%) all-rx and 497 (19.5%) new-rx patients have never interrupted ada treatment for >70 days or permanently discontinued ada. • 2383 (39.4%) all-rx and 1182 (46.3%) new-rx patients discontinued from the registry; the most frequent reason for discontinuation was being lost to follow-up (18.2%, all-rx and 23.9%, new-rx; table 2). table 2. reasons for discontinuation from registry and registry drug (all-rx and new-rx patient populations) reason for discontinuation (in >1% patients) all-rx n=6045 n (%) new-rx n=2554 n (%) from registrya, any reason 2383 (39.4) 1182 (46.3) lost to follow-up 1100 (18.2) 611 (23.9) withdrew consent 521 (8.6) 219 (8.6) lack of efficacy 98 (1.6) 63 (2.5) death 95 (1.6) 36 (1.4) patient moved 98 (1.6) 39 (1.5) noncompliant 98 (1.6) 64 (2.5) other 472 (7.8) 189 (7.4) from registry drugb, any reason 3551 (58.7) 1763 (69.0) lack of efficacy 1286 (21.3) 692 (27.1) lost to follow-up 757 (12.5) 407 (15.9) withdrew consent 376 (6.2) 152 (6.0) ae 188 (3.1) 95 (3.7) sae or sae of interest 114 (1.9) 47 (1.8) other 778 (12.9) 333 (13.0) areasons for registry discontinuations in ≤1% of patients were ae, intolerance, sae or sae of interest, satisfactory improvement, pregnancy, or unknown. breasons for registry drug discontinuations in ≤1% of patients were intolerance, patient moved, satisfactory improvement, patient death, noncompliance, pregnancy, required additional therapy, or unknown. ae=adverse event; all-rx=all-treated patient population; new-rx=new prescription patient population; sae=serious ae. • median (range) duration of overall exposure to ada was 1430 (14–5161) and 657.5 (14–2947) days for all-rx and new-rx patient populations, respectively. • median (range) duration of registry exposure to ada was 1077 (14–2947) and 656 (14–2947) days for all-rx and new-rx patient populations, respectively. • the number of patients according to duration of overall exposure to ada and registry exposure to ada are shown in figure 2. figure 2. number of patients based on duration of ada exposure (all-rx and new-rx patient populations) 0188413396621936new-rx, n=2554 0191412396626new-rx, n=2554 929 1274 1304 1013 1115all-rx, n=6045 all-rx, n=6045 1740 1316 1187 1372 ≤1 y >1 to 3 y >3 to 5 y >5 to 7 y 1015 430 >7 to 9 y 324 >9 y ≤1 y >1 to 3 y >3 to 5 y >5 to 7 y >7 to 9 y >9 y 0 number of patients based on their overall exposure to ada (outside of and within the registry) number of patients based on their registry exposure to ada (within the registry) ada=adalimumab; all-rx=all-treated patient population; new-rx=new prescription patient population. • time to discontinuation from the registry and from registry drug in all-rx and new-rx patients is shown in figure 3. figure 3. time to discontinuation from the registry and from registry drug (ada, all-rx, and new-rx patient populations) 0 0.0 0.1 0.2 0.4 0.6 0.8 1.0 monthsa p ro b a b ili ty o f r e m a in in g in t h e r e g is tr y o r o n r e g is tr y d ru g continuations patients total, n failed, n censored, n (%) registry 6045 2383 3662 (60.6) registry drug 6045 3551 2494 (41.3) 12 24 36 48 60 72 84 96 all-rx new-rx all-rx new-rx registry 2554 1182 1372 (53.7) registry drug 2554 1763 791 (31.0) atime of observation (first day to last day of registry participation) was used for time to registry discontinuation; registry exposure to adalimumab was used for time to registry drug discontinuation. all-rx=all-treated patient population; new-rx=new prescription patient population. presented at the fall clinical dermatology conference 36th anniversary • las vega, nevada • october 12 – 15, 2017 long-term safety and effectiveness of adalimumab for moderate to severe psoriasis: results from the eight-year interim analysis of the esprit registry diamant thaçi,1 alan menter,2 jashin j. wu,3 dilek arikan,4 hartmut kupper,5 mareike bereswill,5 wendell c. valdecantos4 1comprehensive center for inflammation medicine, university medical school schleswig holstein, campus lübeck, germany; 2division of dermatology, baylor university medical center, dallas, tx, united states; 3kaiser permanente los angeles medical center, los angeles, ca, united states; 4abbvie inc., north chicago, il, united states; 5abbvie deutschland gmbh & co kg, ludwigshafen, germany introduction • adalimumab (ada), a fully human, recombinant, monoclonal antibody directed against tumor necrosis factor-α (tnf-α), is indicated for the treatment of moderate to severe chronic plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy.1 • esprit (nct00799877) is an ongoing, 10-year international prospective observational registry evaluating the long-term safety and effectiveness of originator ada prescribed in routine clinical practice according to local product labeling for adult patients with chronic plaque psoriasis.2 objective • to report the interim analysis of long-term safety and effectiveness of ada treatment over the initial 8 years of the esprit registry (26 september 2008–30 november 2016). materials & methods study design and patients • enrollment: – patient enrollment was initiated on 26 september 2008 and completed on 8 november 2012. – as of 30 november 2016, 6066 patients were enrolled and 6045 patients were analyzed in the esprit registry. – study sites were located in the united states, canada, austria, the czech republic, denmark, france, germany, greece, ireland, the netherlands, spain, sweden, and the united kingdom. • treatment: ada was dosed as recommended in the local product label. • main inclusion criteria (figure 1): – adult patients (≥18 years) with chronic plaque psoriasis who have been prescribed ada according to local product labeling and meet one of the following criteria: ■ previously initiated ada therapy and continued on ada with no more than 70 consecutive days off drug. • the initial ada dose was received either in a preregistry feeder clinical trial or from an existing prescription outside of a pre-registry feeder trial. • source documentation of serious adverse events (saes), aes of special interest, and dosing information since the initiation of therapy could be provided by the physician. ■ newly initiated ada therapy within 4 weeks of registry entry. statistical analyses • populations (figure 1): – all-treated (all-rx) patient population: patients who received at least 1 dose of ada in the registry and were analyzed. ■ new-prescription (new-rx) patient population: patients who newly initiated ada within 4 weeks prior to registry enrollment. • descriptive statistics are presented for baseline patient demographics and disease characteristics. figure 1. study design and patient population of esprit observational registry esprit registry (p10-023); start date: sep 2008 adalimumab treatment per local product label 1 2 3 4 106 9875 ** ** * * * * * * * * * * * * * * * * * * 0 enrollment, y newly initiated adalimumab initial dose ≤4 wk pre-registry • new prescription (new-rx) patients (n=2554) – 1– 2– 3– 4– 5– 6 all-treated (all-rx) patients (n=6045)a patients who received at least 1 dose in the registry and were analyzed initiated adalimumab in the past initial dose >4 wk pre-registry • has participated in a pre-registry feeder trialb (n=386) • has never participated in a pre-registry feeder trial (n=3105) phase 3 m02-570 (n=1) jun 2003 reveal m03-656 (n=3) dec 2004 believe m10-060 (n=73) nov 2007 phase 3 m06-808 (n=1) jun 2006 champion m04-716 (n=2) jul 2005 pride w10-151 (n=62) sep 2007 ole c m03-658 (n=196) may 2004 reach m10-405 (n=23) aug 2008 progress m10-238 (n=25) jan 2008 astart dates are shown for clinical trials. breveal and champion were among the feeder trials for the ole; the number of patients in these trials was counted separately from the 196 patients in the ole. *patients were evaluated 3 and 6 months post enrollment, then every 6 months for ≤10 years. patients are followed at intervals determined by routine clinical practice or as recommended by national guidelines. safety data are captured during the entire study period. patients who discontinue registry drug are encouraged to remain in the registry. ole=open-label extension. • smr was 0.34 (95% ci, 0.25–0.46) for all-rx and 0.38 (95% ci, 0.22–0.62) for new-rx, indicating that the observed number of deaths was below expected for age-, sex-, and country-matched population (figure 4). figure 4. standardized mortality ratios (smrs), overall and by gender (all-rx and new-rx patient populations) 0.01 0.1 1 a llr x p o p u la ti o n 0.28 0.410.18 0.47 0.740.28 0.34 0.460.25 men women total 0.01 0.1 1 standardized mortality ratio (95% ci) n e w -r x p o p u la ti o n 0.30 0.600.13 0.52 1.020.22 0.38 0.620.22 men women total death rate lower than expected death rate higher than expected n py expected observed deaths, n deaths, n 3485 12236.8 86.6 24 2560 7423.2 40.2 19 6045 19660.0 126.8 43 1376 4263.7 26.4 8 1178 2797.5 15.4 8 2554 7061.2 41.8 16 all-rx=all-treated patient population; new-rx=new prescription population; py=patient-years. safety • the incidence rates (e/100py) of all-teaes of interest in all-rx patients by periods of overall exposure to ada at the time of ae onset remained stable over time (table 3). table 3. incidence rates of all-teaes of interest by periods of overall exposure to ada (all-rx patient population) overall exposure to ada at the onset of ae (years) overall0 – <1a 1 – <2 2 – <3 3 – <4 4 – <5 5 – <6 6 – <7 7– <8 8 –<9 ≥9b ae of interest n= 6045 4779 3995 3470 2983 2461 1943 1347 671 324 6045 e (e/100py) py= 5363.0 4347.6 3716.8 3221.1 2738.3 2192.2 1660.8 1020.3 485.6 522.1 25268.1 ae 1724 (32.1) 923 (21.2) 877 (23.6) 753 (23.4) 459 (16.8) 299 (13.6) 222 (13.4) 130 (12.7) 68 (14.0) 93 (17.8) 5548 (22.0) ae leading to d/c of ada 164 (3.1) 72 (1.7) 61 (1.6) 47 (1.5) 40 (1.5) 15 (0.7) 19 (1.1) 7 (0.7) 3 (0.6) 8 (1.5) 436 (1.7) serious ae 249 (4.6) 186 (4.3) 189 (5.1) 152 (4.7) 130 (4.7) 80 (3.6) 65 (3.9) 40 (3.9) 20 (4.1) 31 (5.9) 1142 (4.5) serious infection 64 (1.2) 41 (0.9) 41 (1.1) 28 (0.9) 32 (1.2) 20 (0.9) 12 (0.7) 6 (0.6) 4 (0.8) 8 (1.5) 256 (1.0) oral candidiasis 7 (0.1) 1 (<0.1) 1 (<0.1) 0 0 0 0 0 0 0 9 (<0.1) active tuberculosis 3 (<0.1) 0 1 (<0.1) 0 1 (<0.1) 0 0 0 0 0 5 (<0.1) opportunistic infection, otherc 1 (<0.1) 0 0 0 1 (<0.1) 0 2 (0.1) 0 0 0 4 (<0.1) malignancy 54 (1.0) 46 (1.1) 41 (1.1) 37 (1.1) 35 (1.3) 20 (0.9) 22 (1.3) 14 (1.4) 6 (1.2) 7 (1.3) 282 (1.1) congestive heart failure 3 (<0.1) 1 (<0.1) 2 (<0.1) 3 (<0.1) 2 (<0.1) 0 1 (<0.1) 0 0 0 12 (<0.1) lupus-like reactions and systemic lupusd 6 (0.1) 0 0 4 (0.1) 0 0 0 0 0 0 10 (<0.1) demyelinating disorder 2 (<0.1) 0 2 (<0.1) 0 0 1 (<0.1) 0 0 0 0 5 (<0.1) ae leading to death 8 (0.1) 12 (0.3) 6 (0.2) 5 (0.2) 2 (<0.1) 2 (<0.1) 4 (0.2) 2 (0.2) 3 (0.6) 0 44 (0.2) athe aes collected from rollover patients during feeder studies most likely occurred in the first years of overall exposure to adalimumab. a closer ae documentation in feeder studies is expected compared with registry ae collection and retroactive collection of aes for patients who initiated adalimumab therapy outside of an abbvie clinical trial before the registry. bpatients with ≥9 years of overall exposure to adalimumab are a selected subgroup from the overall population who had longest exposure to adalimumab and potentially had a longer duration of disease. cexcluding oral candidiasis and tuberculosis. dthere were no reports of drug-induced lupus among the 7 patients with 10 events of lupus-like reactions and systemic lupus during the registry. all-teae=all treatment-emergent adverse event; all-rx=all-treated patient population; ae=adverse event; ada=adalimumab; d/c=discontinuation. effectiveness • 45.0%–65.5% of all-rx and 50.0%–64.2% of new-rx patients achieved a pga score of “clear” or “minimal” during years 1–8 of registry participation (figure 5). figure 5. proportion of patients achieving pga “clear” or “minimal” over years 1–8 (all-rx and new-rx patient populations: as observed) 12 24 36 48 60 72 84 96 0 20 40 60 80 100 registry participation, months p a ti e n ts ,% 57.0 58.7 59.1 62.6 61.9 63.8 65.5 45.0 n= na= new-rx (n=2554)all-rx (n=6045) 52.8 55.5 56.3 59.5 59.9 63.2 64.2 50.0 2635 4624 983 1862 2376 4048 881 1588 2090 3537 767 1363 1994 3185 724 1216 1496 2415 571 953 1114 1745 425 673 428 653 217 338 9 20 8 16 na=number of patients with non-missing pga data at the respective visit; all-rx=all-treated patient population. new-rx=new prescription population; pga=physician global assessment. results (continued) disclosures & acknowledgments d. thaçi has received honoraria from abbvie, amgen, biogen-idec, celgene, gsk, dignity, janssen, leo, maruho, mitsubishi, lilly, novartis, pfizer, regeneron/sanofi, and ucb for participation on advisory boards, as a speaker, and for consultancy; and received research grants from abbvie, biogen-idec, leo, and pfizer. a. menter has received grants and honoraria from abbvie, amgen, janssen biotech, inc., and leo pharma for service on an advisory board, as consultant, investigator, and speaker; received grants and honoraria from allergan for service on an advisory board and as a consultant and from eli lilly for service on an advisory board and as a consultant and investigator; received grants and honoraria from boehringer ingelheim for service on an advisory board and as an investigator; received grants and honoraria from novartis and pfizer for service as a consultant and investigator; received grants from celgene, dermira, merck, neothetics, regeneron, and syntrix for service as an investigator; and received honoraria from galderma for service as a consultant. j. j. wu is an investigator for abbvie, amgen, eli lilly, janssen, novartis, and regeneron. d. arikan, h. kupper, m. bereswill, and w. c. valdecantos are full-time employees of abbvie and may own stock/options. abbvie funded the esprit study (nct00799877), contributed to its design, and participated in data collection, analysis, and interpretation of the data and in writing, review, and approval of this presentation. medical writing support was provided by deepa venkitaramani, phd, of abbvie and richard m. edwards, phd, and janet matsuura, phd, of complete publication solutions, llc (north wales, pa, usa). abbvie funded the medical writing support. conclusions ■ no new safety signals were observed with ada treatment during this 8-year interim analysis, and safety was consistent with the known safety profile of ada. ■ incidence rates of serious infections and malignancies remained stable with up to >8 years of overall exposure to ada. ■ the number of treatment-emergent deaths in the registry was below the expected rate compared with the general population. ■ as-observed effectiveness of ada remained stable through 96 months. references 1. humira® (adalimumab). full prescribing information, abbvie inc., north chicago, il, 2016. 2. menter a, et al. j am acad dermatol. 2015;73(3):410-19.e6. fc17posterabbviethacilongtermsafety8yearinterim.pdf skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 497 original research analyzing the relationship between altmetric score and literature citations in the dermatology literature meredith thomley, bs1, ana preda-naumescu, bs1, carter j. boyd, md, mba1*, tiffany mayo, md2 1school of medicine, university of alabama at birmingham, birmingham, al 2assistant professor, department of dermatology, university of alabama at birmingham, birmingham, al *equal contribution as primary authors scientific research furthers our wealth of medical knowledge and can enact clinical change. the question stands of how the impact of a single article can be determined. various metrics seek to describe this impact. the publishing journal’s impact factor (if) and the article’s citation count have traditionally served as the quantitative measures of an article’s impact.1 these two metrics have limitations with the former yielding a generalization marker based on the journal rather than the article, and the latter making it difficult for authors and peers to see the true impact of a publication until years later, when substantial citation information has been accrued.2,3 abstract background: standard bibliometric methods used in dermatologic research include impact factor and citations. the altmetric score is an adjunctive measure of article impact. objectives: the purpose of this study is to examine the breadth of societal impact made by scientific articles in dermatology and investigate a correlation between an article’s impact factor and citations, with its altmetric score. methods: we reviewed 15 dermatology journals with the highest impact factors and analyzed the 10 most cited articles from 2013 and 2016 within those journals. we studied the articles’ altmetric scores, number of citations, and social media mentions. using microsoft excel, we performed statistical analysis with pearson correlation coefficients and descriptive statistics. results: analysis revealed a significant positive relationship between citation count and altmetric scores for articles published in 2013 (p=0.0009) and 2016 (p=0.003). impact factor was also significantly associated with altmetric scores across both years (p=0.002, p=0.0005). conclusions: altmetric score weakly corresponded with citation count and journal impact factor across cohorts. we conclude that altmetric scores serve as an additional measurement of article impact in dermatology, though they are insufficient as a replacement for traditional measures at this time. introduction skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 498 the platform altmetric first published its rating scale, the altmetric score, in 2010.4 this algorithm gives a numerical score to articles’ combined influence across mixed media platforms, including mentions from twitter to facebook, new outlets to public policy documents, video sources to reddit, and others.5 altmetric incorporates the digital distribution and publicity for a scientific article, grading each article based on individual mentions across platforms. the mentions are converted into a total index measure of attention and impact, useful for standardization of bibliometric data collection. the score does not measure the quality of the research, the researcher, or the attention an article has accrued, but it is useful for measuring the article’s visibility and overall reach, with a higher score indicating a greater overall reach.4 to say a higher score is better, or alternatively worse, than a lower score is subjective the score measures attention which can itself be ‘good or bad.’ while there are not cutoffs such as a maximum or minimum possible score, it is always a whole number.4 we propose the use of the altmetric score as a timely and accurate proxy measure for article impact, correlating with the traditional metrics of if and citations. in a society with the world of information in the palm of one’s hand, journal impact factor and an article’s citation count cause a delay in data that is contrary to modern standards. social media platforms and the internet at large are granted immediate access to research articles by a simple web search. by drawing on alternative metric ratings, a more rapid picture of the impact of a published research article can be established. the authors selected the top 15 journals by impact factor in dermatology for inclusion in this study. the list was gathered by searching “dermatology” in elsevier’s citescore in the scopus database.7 these journals include: journal of investigative dermatology, pigment cell & melanoma research, journal of the american academy of dermatology, jama dermatology, acta dermavenereologica, experimental dermatology, british journal of dermatology, contact dermatitis, journal of dermatological science, journal of the european academy of dermatology, wound repair and regeneration, american journal of clinical dermatology, dermatologic surgery, seminars in cutaneous medicine and surgery, and journal of dermatology. we extracted data on twitter presence of each of these journals, noting whether or not the journals had accounts, and if so, how long have they been active. this study also determined journal if, acquired from journal citation reports (jcr), across two cohorts: 2013 and 2016.6 2013 was chosen to yield a six-year interim to present day, the citations after this allotted time correlate with 90% total citations. data from 2016 allows for better comparison to a modern altmetric algorithm, though citation count three-years postpublication is 75% predictive of total citations.7 the ten most cited articles in each journal were analyzed for bibliometric data; the sets of ten were identified by utilizing elsevier’s scopus.8 150 total articles were analyzed. the altmetric attention score was calculated by using the altmetric bookmarklet, available for download through the altmetric website. altmetric scores were recorded for each article across 2013 and 2016. specific social media and digital dispersion data were collected on the following platforms: twitter, facebook, blogs, policy sources, wikipedia, reddit, videos, google+, and research highlights.4 methods skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 499 all data was gathered and analyzed via microsoft excel; statistical significance was determined by p-value <0.05. pearson’s correlation coefficient (r) was used to establish correlation between variables; the coefficient of determination (r2) was used to measure the amount of variance in these correlations. this study largely modeled its methods, procedures, and analysis from examples in pediatric surgery, general surgery, and urology literature, also comparing altmetric score to citation and impact factor.7,9,10 from the 15 dermatology journals with the highest impact factor based on the jcr, the 10 most highly cited articles published in 2013 and 2016 were reviewed (table 1). thus, 150 articles were reviewed from each year. in 2013, the cumulative total of citations for all articles was 13,819 and the total altmetric attention score was 2,397. the median number of citations for each individual article was 62 with a range from 16854 (standard deviation 80.1). the median altmetric attention scores for each individual article was 3 with a range from 0-396 (standard deviation 51.7). citation number and journal impact factor demonstrated a significant positive correlation in the 2013 cohort (r = 0.463, p<0.0001). analysis revealed a significant positive relationship between citation count and altmetric attention scores for articles published in 2013 (r=0.267, p=0.0009) and a significant positive relationship between altmetric attention scores and journal impact factor for the same cohort of articles (r=0.255, p=0.002) (figure 1 a, b). r2 was low for both correlations: r2=0.072 for citations and r2=0.065 for impact factor. journals were also studied in isolation to calculate the correlation coefficient between citation number and altmetric attention score (table 2). in 2013, only acta dermatovenereologica (r=0.891, p=0.0005) and seminars in cutaneous medicine and surgery (r=0.985, p<0.0001) had significant correlations between their articles’ citation count and altmetric attention scores. the remainder were not significant, though two others approached statistical significance. to compare the evolution across time, data was also collected in 2016. total citation count for 2016 was 6,717 compared to the 13,819 for 2013, a 51.4% decline. the total altmetric attention score was 2,397 in 2013 but climbed by 60.3% to a score of 3,843 in 2016. median number of citations in 2016 was 31.5 ranging from 8-425 (standard deviation 42.9), whereas the median altmetric score in 2016 was 2.5 with a range of 0-509 (standard deviation 83.6). altmetric ratings were significantly correlated with citation count for the 2016 cohort (r=0.244, p=0.003). impact factor was significantly associated with altmetric attention scores as well (r=0.283, p=0.0005). r2 was minimal for both, 0.060 for citation count and 0.080 for journal impact factor in 2016. the journals from 2016 were likewise studied individually to calculate the correlation coefficient between citation count and altmetric score (table 2). five of the 15 journals had significant correlations between their articles’ citation count and article altmetric attention score in 2016. these journals were journal of investigative dermatology (r=0.935, p<0.0001), journal of the american academy of dermatology (r=0.797, p=0.006), experimental dermatology (r=0.727, p=0.02), journal of dermatological science (r=0.843, p=0.0002), and journal of dermatology (r=0.723, p=0.017). nine of the 15 journals had twitter accounts at the time of review (table 1). average age of the results skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 500 table 1. categorization of dermatology journal bibliometric and altmetric data. journal citations (median [range]) altmetric score (median [range]) journal impact factor (2013) journal impact factor (2016) age of twitter account (y) journal of investigative dermatology 160.5 [120854] 8.5 [1-277] 6.372 6.287 7.33 pigment cell & melanoma research 55 [46-164] 2 [0-17] 5.641 5.17 n/a journal of the american academy of dermatology 151 [107-276] 12.5 [1-396] 5.004 7.002 4.08 jama dermatology 129 [91-203] 28.5 [2-323] 4.970 5.817 0 acta dermatovenereologica 40.5 [32-144] 1 [0-12] 4.244 3.653 8.25 experimental dermatology 52.5 [47-115] 1 [0-23] 4.115 2.532 2.67 british journal of dermatology 172 [101-233] 5 [1-85] 4.1 3.605 6.17 contact dermatitis 62 [48-70] 4 [0-11] 3.624 4.335 0.5 journal of dermatological science 57 [40-172] 0 [0-4] 3.335 3.733 n/a journal of the european academy of dermatology and venereology 90.5 [74-196] 4 [1-51] 3.105 3.528 0.42 wound repair and regeneration 62 [37-99] 1 [0-16] 2.768 3.041 n/a american journal of clinical dermatology 53.5 [37-142] 7.5 [1-26] 2.519 2.755 n/a dermatologic surgery 47 [41-62] 3 [1-13] 2.467 2.351 n/a seminars in cutaneous medicine and surgery 22 [16-205] 2 [0-81] 2.402 1.317 1.92 journal of dermatology 40 [35-51] 1 [0-12] 2.354 2.094 n/a twitter accounts was 3.5 years. acta dermato-venerologica had the oldest twitter account (established in 2011), while jama dermatology just recently established a twitter account in 2019 around the time of this study. older twitter accounts were not significantly associated with increasing correlations between altmetric attention score and bibliometrics in both cohorts: 2013 (r=0.012, p=0.783) and 2016 (r=0.0002, p=0.973) (figure 2). dissecting the components comprising the altmetric attention score in 2013 revealed that twitter, news outlets, and facebook were the top three platforms in which articles received mentions. this rank order for article mentions remained the same skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 501 figure 1. altmetric comparisons with citation count and journal impact factor by year. a. altmetric significantly correlates with citation count for articles published in 2013 (p = 0.0009). b. altmetric demonstrated a significant positive association with journal impact factor for articles published in 2013 (p = 0.002). c. altmetric attention scores have a significant positive correlation with citation count for articles published in 2016 (p = 0.003). d. altmetric attention scores have a significant positive correlation with journal impact factor for articles published in 2016 (p = 0.0005). r2 – a. 0.0715; b. 0.0651; c. 0.0594; d. 0.0798 in 2016 (table 3). twitter was the clear leader for mentions received in both years with 180% more mentions than the second most utilized platform in 2013, though this margin diminished slightly in 2016 to 145%. between the two years, twitter (85.7%), news outlets (109.7%), reddit (100%), and google + (84.6%) saw increases in mentions. all of the remaining platforms’ mentions decreased in 2016 compared to 2013 (table 3). to date, the influence of an article has been based on both the if of the journal and the number of citations. however, because citation information accrues over time, the delayed citation counts yield an interim during which the actual impact of an article cannot be yet determined.2,3 for a more modern approach, the altmetric score takes into account the overall popularity of an article in real time by examining its mixed media influence. this is done based off of a variety of measures, such as twitter, facebook, wikipedia mentions, google+, news outlets, etc. we posited that the altmetric score could predict and parallel the total impression of an article by acting as a proxy for if and citation count in the top dermatology journals. this study is the first, to the authors’ knowledge, to examine these various bibliometric methods in the field of dermatologic research. our findings indicate a positive correlation between the modern platform, altmetric scores, with previously standard methods, if and citations, in both year cohorts. however, the correlation was determined by low r2 coefficients which discussion c. d. a. b. skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 502 table 2. summary of journal twitter accounts and comparisons between bibliometrics and altmetrics for the journals of study in 2013 and 2016. journal year twitter created correlation coefficient between number of citations and altmetric score (2013) p-value (2013) correlation coefficient between number of citations and altmetric score (2016) p-value (2016) journal of investigative dermatology 2012 0.02 0.95 0.93 <0.0001 pigment cell & melanoma research n/a 0.11 0.77 0.005 0.99 journal of the american academy of dermatology 2015 0.0006 0.99 0.80 0.006 jama dermatology 2019 0.58 0.08 -0.29 0.42 acta dermatovenereologica 2011 0.89 0.0005 -0.11 0.75 experimental dermatology 2016 -0.15 0.69 0.73 0.02 british journal of dermatology 2013 0.47 0.17 -0.17 0.63 contact dermatitis 2019 -0.18 0.63 -0.28 0.42 journal of dermatological science n/a 0.59 0.073 0.84 0.0002 journal of the european academy of dermatology and venereology 2019 -0.28 0.44 0.24 0.50 wound repair and regeneration n/a -0.23 0.51 0.54 0.11 american journal of clinical dermatology n/a -0.006 0.99 0.28 0.44 dermatologic surgery n/a -0.01 0.97 -0.20 0.57 seminars in cutaneous medicine and surgery 2017 0.98 <0.0001 n/a n/a journal of dermatology n/a -0.06 0.87 0.72 0.02 suggests that citation count and journal impact factor are not entirely explained by article altmetric attention score. while altmetric attention scores may be broadly predictive of the impact of an article, they are not an all-inclusive bibliometric for journal impact and citation count. altmetric scores show attention or engagement with an article, whether that be positive or negative, as opposed to the quality of the article’s impact as far as its implications for traditional scientific research. in order to fully evaluate the scientific and societal contributions of an article, a comparison between altmetric and the more traditional methods can yield complementary perspectives and a better gage of overall impact. skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 503 figure 2. relationship between the twitter account age and the correlation coefficients between citation number and altmetric attention score. longer-established twitter accounts were not associated with increased correlation between altmetric attention score and bibliometric factors for the dermatology journals in 2013 (a, p = 0.95) or 2016 (b, p = 0.81). r2 – a. 0.0115; b. 0.0002 table 3. classification of social media utilization factoring into the cumulative altmetric score for journals by year. source article "mentions" in 2013 article "mentions" in 2016 percent change (%) twitter 512 951 85.74 facebook 159 139 -12.57 blog 30 5 -83.33 policy source 20 9 -55.00 news outlets 185 388 109.7 wikipedia 28 14 -50 reddit 2 4 100.00 videos 23 2 -91.30 patents 87 7 -91.95 google + 13 24 84.62 research highlight platforms 20 18 -10.00 a. b. skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 504 when studying journals in isolation, 2 of the 15 showed a significant correlation between citation number and altmetric attention score in 2013, while 5 of the 15 demonstrated a significant correlation between citation number and altmetric score in 2016. with the continued growth of social media and digital involvement in research publicity over time, it could be that altmetric attention scores will follow this trend towards becoming more representative, rather than simply complementary, in describing a journals’ impact. however, the minority of journals achieved significant correlation in this way, suggesting that the altmetric algorithm does not entirely explain impact for top dermatology journals. additionally, twitter was demonstrated to be the key platform to increasing engagement of dermatology research articles. twitter exceeded all other social media platforms in its mentions, in both 2013 and 2016. the majority of journals studied in this case had a twitter presence for an average of 3.5 years, with accounts created between 2011 and 2019. interestingly, the older twitter accounts did not display increased correlations between altmetric and traditional impact metrics. moving forward, further studies of true twitter activity and engagement could be more indicative of correct correlation, rather than simply length of account life. with twitter, news outlets, and facebook contributing largest to altmetric score, authors and publishers might draw upon this information to concentrate marketing efforts to augment article impact in the future. these three platforms prove to be popular amongst dermatology researchers and publishers. furthermore, it is important to note that across the three-year-time period, twitter, news outlets, reddit, and google+ all displayed increasing trends in mentions, indicative of the expanding online presence for scientific research. the total altmetric attention score for the 2016 cohort of articles was 60.3% higher than in 2013, whereas article citation counts were 51.4% lower in 2016 than 2013. the fewer citations by the 2016 cohort is attributable to the decrease in time for these articles to accrue citations. the increased volume of altmetric score coincides with the ever-growing use of media incorporation into article impact. as the evolution of media continues to infiltrate the world of scientific research, we predict the weak correlation between traditional measures and altmetric scores to grow stronger. article “impact” describes an amalgam of factors, including journal notability, citation count, media mentions, and web dissemination. the benefit to utilizing the altmetric score is the speed at which one can sum up these various contributing factors to quantify a research article’s success. though, based on our findings, it cannot wholly describe the final impact of an article in the field of dermatology, it can contribute to the overall picture of how the article is performing in present day, based on social media standards. evaluating the impact of a scientific article accurately is important for authors and readers alike. by quantifying the number of mentions, shares, reposts, and citations into a standardized metric, a publication can be more appropriately graded, compared, and applied clinically. bibliometric data has traditionally been based on journal if and citation accumulation; however, alternative metric ratings have emerged as a way to incorporate social media and online presence into the overall measurement of an article’s impact. the altmetric score, draws on media conclusion skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 505 platform information, which traditional metric patterns exclude. altmetric method provides a quicker analysis of impact than the previous metrics could provide via long-term citation accumulation and positively, yet weakly, correlates with previous methods of measuring an article’s impact, such as if and citations. altmetric data may be used as a supplementary measure of article success, but not as a substitution to journal if and citations in top dermatologic journals. conflict of interest disclosures: none funding: none corresponding author: meredith thomley, bs department of dermatology university of alabama at birmingham faculty office tower 1107 510 20th street south birmingham, al 35249 phone: 205-937-8135 email: thomley@uab.edu references: 1. durieux v, gevenois p. bibliometric indicators: quality measurements of scientific publication. radiology. 2010;255(2):342-351. 2. bornmann l ll. scientometrics in a changing research landscape: bibliometrics has become an integral part of research quality evaluation and has been changing the practice of research. embo rep. 2014;15:1228e1232. 3. wang j. citation time window choice for research impact evaluation. scientometrics. 2012;94(3):851-872. 4. altmetric. altmetric website. https://www.altmetric.com. accessed august 2019. 5. elmore s. the altmetric attention score: what does it mean and why should i care?. toxicol pathol. 2018;46(3):252-255. 6. journal citation reports, clarivate analytics. available at: https://incites.clarivate.com. accessed august 2019. 7. chang j, desai n, gosain a. correlation between altmetric score and citations in pediatric surgery core journals. journal of surgical research. 2019;243:52-58. 8. scopus sources, elsevier. available at: https://www.scopus.com/sources. accessed august 2019. 9. nocera, a. p., boyd, c. j., boudreau, h., hakim, o., & rais-bahrami, s. (2019). examining the correlation between altmetric score and citations in the urology literature. urology. doi: 10.1016/j.urology.2019.09.014 10. mullins, c. h., boyd, c. j., & corey, b. l. (2020). examining the correlation between altmetric score and citations in the general surgery literature. journal of surgical research, 248, 159–164. retrieved january 13, 2020, from 10.1016/j.jss.2019.11.008 https://www.scopus.com/sources.%20accessed%20august%202019 https://www.scopus.com/sources.%20accessed%20august%202019 acknowledgements: medical writing support was provided by prescott medical communications group (chicago, il) with financial support from ortho dermatologics; ortho dermatologics is a division of bausch health us, llc | 2020 fall clinical dermatology conference® for pas & nps • april 3-5, 2020 • orlando, fl synopsis ◾ psoriasis is a chronic, immune‑mediated disease that can have exacerbations and remissions1 ◾ topical therapy is the mainstay of treatment for patients with localized psoriasis2; however, long‑term continuous use of topical corticosteroids is not recommended due to the potential for local adverse events1 ◾ though applying topicals to large areas in more severe disease may not be practical for patients with very high affected body surface area (bsa), there is limited data on the efficacy of topical treatments in more localized severe plaque psoriasis ◾ data from phase 3 clinical trials have shown the ef ficacy and tolerability of a fixed combination lotion containing halobetasol propionate 0.01% and tazarotene 0.045% (hp/taz; duobrii® ortho dermatologics, bridgewater, nj) over 8 weeks in participants with localized moderate‑to‑severe plaque psoriasis3,4 objective ◾ to investigate long‑term maintenance of treatment effect following cessation of once‑daily hp/taz lotion in a subgroup of participants with higher levels of affected bsa (6 –12%) methods ◾ this was a 1‑year multicenter, open‑label study (nct02462083) in participants aged ≥18 years with moderate‑to‑severe plaque psoriasis • investigator’s global assessment (iga) score of 3 or 4 and an affected bsa of 3 –12% were required for study enrollment • in this study, cerave® hydrating cleanser and cerave® moisturizing lotion (l’oreal, ny) were provided as needed for optimal moisturization/cleaning of the skin ◾ participants were treated with hp/taz lotion once‑daily for 8 weeks and intermittently in 4‑week intervals for a maximum continuous exposure of 24 weeks (figure 1) • at week 8, participants who achieved treatment success stopped treatment; those who did not achieve treatment success were treated for 4 additional weeks • all participants were re‑evaluated at week 12; those demonstrating ≥1‑grade improvement in baseline iga continued the study and were subsequently managed in 4‑week cycles • if they had not achieved treatment success, they were treated once daily with hp/taz lotion • if they had achieved treatment success, they received no treatment until the next evaluation ◾ a post hoc analysis was conducted to investigate maintenance of effect with hp/taz lotion in a subgroup of participants with higher baseline bsa (6 –12%); results from the overall study population (bsa 3 –12%) were included for comparison long-term management of moderate-to-severe plaque psoriasis: maintenance of treatment success following cessation of fixed combination halobetasol propionate 0.01% and tazarotene 0.045% (hp/taz) lotion in patients with baseline body surface area of 6 -12% figure 1. open-label study design screening successa treatment stopped for 4 weeks no success continued once-daily hp/taz for 4 weeks improvementb continued study and managed in 4-week cycles for up to 1 year, with patients re-evaluated every 4 weeks for treatment successa no improvement discontinued from study oncedaily hp/taz 1 yearweek 24 if continuous treatment was received, iga score of 0 or 1 needed to continue study day 0 week 12 evaluated for ≥1-grade improvement from baseline iga week 8 evaluated for treatment successa maximum continuous exposure was 24 weeks. atreatment success defined as score of 0 or 1 on iga (clear or almost clear). bimprovement defined as ≥1-grade improvement from baseline iga. hp/taz, halobetasol propionate 0.01%/tazarotene 0.045%; iga, investigator’s global assessment. results ◾ a total of 555 participants were included in the study, of which 210 (37.8%) had baseline bsa levels of 6 –12% (figure 2) figure 2. baseline bsa in participants treated with hp/taz (n=555) 4% (n=103) 5% (n=97) 6% (n=51) 7% (n=30) 8% (n=36) 10% (n=45) 12% (n=23) 11% (n=12) 9% (n=13) 3% (n=145) 3–5% bsa 6–12% bsa bsa, body surface area; hp/taz, halobetasol propionate 0.01%/tazarotene 0.045%. ◾ at week 8, bsa ≤5% was achieved by 79% of the overall study population (baseline bsa 3 –12%) and 50% of participants with baseline bsa 6 –12% ◾ this reduction in bsa was maintained in those who participated in the study for at least 1 year (figure 3) linda stein gold1; jonathan s weiss2; lawrence green3; leon kircik4,5,6; lauren miller7; abby jacobson8; susan harris9 1henry ford hospital, detroit, mi; 2georgia dermatology partners, and gwinnett clinical research center, inc., snellville, ga; 3 george washington university school of medicine, washington, dc; 4indiana university school of medicine, indianapolis, in; 5physicians skin care, pllc, louisville, ky 6icahn school of medicine at mount sinai, new york, ny; 7dermatology specialists of alabama, gadsden, al; 8ortho dermatologics*, bridgewater, nj; 9bausch health us, llc*, bridgewater, nj *bausch health us, llc is an affiliate of bausch health companies inc. ortho dermatologics is a division of bausch health us, llc. figure 3. maintenance of ≤5% or ≤3% affected bsa from week 8 to end of study (safety population) 68.7% 74.6% 36.2% 44.2% 0% 20% 40% 60% 80% 100% 43.1% 50.0% 17.7% 21.4% 0% 20% 40% 60% 80% 100% p e rc e n ta g e o f p ar ti ci p an ts overall study population: baseline bsa 3–12%a post hoc analysis: baseline bsa 6–12%a subjects participating for ≥6 months (n=390) subjects participating for ≥1 year (n=42) subjects participating for ≥6 months (n=130) subjects participating for ≥1 year (n=138) ≤5% bsa ≤3% bsa aonly bsa records considered as occurring on treatment were used in assessing if the percent bsa was maintained. bsa, body surface area; hp/taz, halobetasol propionate 0.01%/tazarotene 0.045%. ◾ of the participants who achieved treatment success during the study (iga score of clear or almost clear), approximately one‑third had bsa ≤1% at treatment success, regardless of bsa severity at baseline (figure 4) figure 4. body surface area at treatment successa (safety population) 0% 20% 40% 60% 80% 100% p e rc e n ta g e o f p ar ti ci p an ts 91.2% 75.2% 55.7% 35.5% ≤5% ≤3% ≤2% ≤1% 74.5% 59.8% 46.1% 33.3% ≤5% ≤3% ≤2% ≤1% body surface area body surface area overall study population: baseline bsa 3–12%b (n=318) post hoc analysis: baseline bsa 6–12%b (n=102) 0% 20% 40% 60% 80% 100% atreatment success defined as score of 0 or 1 on iga (clear or almost clear). b bsa assessments at the treatment success visit were included. all bsa assessments included regardless of whether they were on treatment or not. bsa, body surface area; hp/taz, halobetasol propionate 0.01%/tazarotene 0.045%; iga, investigator’s global assessment. ◾ in those participants who stopped hp/taz therapy after achieving treatment success, maintenance of therapeutic benefit is demonstrated by the extended time to retreatment (table 1) table 1. time to retreatment with hp/taz lotion (safety population) percentage of participants overall study population: baseline bsa 3 –12% (n=226a) post hoc analysis: baseline bsa 6 –12% (n=70a) no retreatment (did not relapse) 6.6% 5.7% no retreatment for ≥85 days 19.5% 12.9% no retreatment for ≥57 days 28.3% 21.4% no retreatment for ≥29 days 55.3% 44.3% a participants still enrolled post 8 weeks in the study and who stopped therapy after achieving treatment success (defined as a score of 0 or 1 on iga). bsa, body surface area; hp/taz, halobetasol propionate 0.01%/tazarotene 0.045%; iga, investigator’s global assessment. conlusions ◾ in participants with moderate‑to‑severe psoriasis and a baseline bsa of 6 –12%, hp 0.01%/taz 0.045% lotion provided rapid and sustained treatment success, with nearly 45% of participants followed for 1 year not requiring retreatment for ≥1 month references 1. weigle n, et al. am fam physician. 2013;87(9):626-633. 2. torsekar r, et al. indian dermatol online j. 2017;8(4):235-245. 3. stein gold l, et al. j am acad dermatol. 2018;79(2):287-293. 4. sugarman jl, et al. j drugs dermatol. 2018;17(8):855-861. author disclosures linda stein gold has served as investigator/consultant or speaker for ortho dermatologics, leo, dermavant, incyte, novartis, abbvie, and lilly. jonathan s weiss is a consultant, speaker, advisor, and/or researcher for abbvie, ortho dermatologics, jansen biotech, dermira, almirall, brickell biotech, dermtech, scynexis. lawrence green has served as consultant, speaker, and/or investigator for arcutis, abbvie, amgen, celgene, dermavant, jannsen, lilly, mc2, novartis, orthoderm, sienna, sunpharma, ucb. leon kircik has acted as an investigator, advisor, speaker, and consultant for ortho dermatologics. lauren miller is speaker for lilly, novartis, amgen, and pfizer. abby jacobson is an employee of ortho dermatologics and may hold stock and/or stock options in its parent company. susan harris is an employee of bausch health us, llc and may hold stock and/or stock options in its parent company. skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 623 compelling comments integrating metagenomics into personalized medicine in dermatology amy huang, md1, sharon a. glick, md1 1department of dermatology, state university of new york downstate medical center, brooklyn, ny recent articles in high-impact scientific journals have examined the complex relationship between human microbiomes and systemic diseases. terms such as the “gut-brain-skin axis”, “gut-joint axis”, and similar iterations, have redefined the context at which we approach disease – that is, not by examining and treating a condition solely from the perspective of the damaged organ or gene, but by understanding how the organ functions or malfunctions in relation to other, seemingly unrelated, biological systems. these systems include the skin and gut microbiomes. metagenomics seeks to expand our understanding of the genetic composition of microbiomes and the crosstalk between bacterial communities and host environment. the integration of metagenomics into personalized medicine in dermatology, which currently does not scrutinize beyond a patient’s genetic content, can be a welcome addition to the arsenal of “-omics” available in assessing a patient’s predicted response to treatment. disturbance of both the skin and gut microbiomes in early life, called “dysbiosis”, is associated with the development of inflammatory and autoimmune skin disorders, such as psoriatic arthritis,1 atopic dermatitis,2-5 and systemic sclerosis.6 studies have shown that altering the microbial composition of a microbiome, such as by fecal transplant in inflammatory gut disorders or by bleach baths in atopic dermatitis, can improve disease resistance and therapy response. the emergence of cancer immunotherapy with immune checkpoint inhibitors, targeting cytotoxic t lymphocyte-associated antigen 4 (ctla-4) and programmed cell death protein 1 (pd1), has prompted research into the abstract there has been a recent focus on the association between human microbiomes and disease development, disease resistance, and therapy response. fecal transplants for inflammatory bowel disease and resistant clostridium difficile infection have demonstrated that manipulating the gut microbiome can be beneficial in treating disease. in dermatology, response to immune checkpoint inhibitors for melanoma therapy are affected by differences in gut microbial composition. bleach baths, which alter the skin microbiome, improve atopic dermatitis. gut dysbiosis, or disturbance of the gut microbiome in early life, have been shown to influence the development of systemic sclerosis and atopic dermatitis. metagenomic sequencing can therefore be a useful addition in personalized medicine to identify therapy responders versus non-responders, patients at risk of serious side-effects from biologics and immune checkpoint inhibitors, and prebiotic supplements that aid in improving therapy. response. skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 624 differences of gut microbiota between responders and non-responders to therapy. three papers published in science have found that the gut microbiome is a major factor in tumor response modulation, in melanoma patients treated with checkpoint inhibitors.7-9 sivan et al. found that melanoma growth was significantly different in two groups of mice harboring distinct gut microbiota, a difference which was eliminated upon cohousing or after fecal transfer from one mouse group to another.8 similarly, gavage with a specific, gutassociated bacteria restored adequate t-cell response in antibiotic-treated and germ-free mice treated with ctla-4 blockade, in a paper by vétizou et al.9 transitioning to human studies, gopalakrishnan et al. used metagenomics to identify significant differences in the diversity, composition, and function of the gut microbiome of responders versus nonresponders to pd-1 blockade.7 murine studies confirmed that a “favorable” gut microbiome can lead to enhanced antitumor immunity and smaller tumor size after immune checkpoint blockade. which types of bacteria comprise this “favorable” microbiome? vétizou et al. suggested an antitumor role of bacteroides fragilis in ctla-4 blockade.9 bacteroides is also associated with resistance to checkpoint blockade-induced colitis in melanoma patients.10 other favorable bacteria included various species of bifidobacterium8, coprococcus1, ruminococcus1, and akkermansia.11 of note, ruminococcus was protective against the development of ige-associated eczema in infants.3 multiple mouse studies have documented the specific effects of each bacterial group in maintaining immune homeostasis, including tnf production, enhanced dendritic cell activation, and stimulating the differentiation of th17 cells to th1 cells.12 in these studies, metagenomic shotgun sequencing of patient stool samples was essential in identifying the microbial composition of responders versus nonresponders, as well as identifying microbes that are potentially protective against disease. although there were discrepancies over which microbial groups were considered favorable, the addition of metagenomics data in anti-cancer personalized medicine could significantly improve decision-making in drug choice and side-effect prevention. metagenomic sequencing could even be expanded to identify responders versus non-responders to biologics in dermatology. once we have an understanding of which microbes are beneficial to therapy, the next step is to customize a cocktail of probiotics that can be administered to augment treatment and to develop an effective mode of delivery. in its current state, metagenomics is overshadowed by the enigma of our own genome – how can we possibly begin to understand the genetics of other organisms when we can barely comprehend that of our own? identification of the most favorable microbial composition would require an expansive human database correlating different bacterial species with clinical response.13 in addition, microbiomes can differ among age groups in certain dermatological conditions, such as in pediatric versus adult atopic dermatitis.14 microbial delivery and engraftment into the host microbiome are other hurdles to overcome. in the clinical setting, the concomitant use of antibiotics and immunomodulators in melanoma and inflammatory or autoimmune skin disorders complicates the use of metagenomic analysis. despite these shortcomings, the skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 625 success of fecal transplant in the clinical setting has demonstrated that manipulating the gut microbiome can provide significant benefits to the patient. conflict of interest disclosures: none funding: none corresponding author: amy huang, m.d. suny downstate medical center department of dermatology 450 clarkson avenue 8th floor box 46 brooklyn, new york 11203 email: amy.huang@downstate.edu references: 1. scher ju, ubeda c, artacho a, et al. decreased bacterial diversity characterizes the altered gut microbiota in patients with psoriatic arthritis, resembling dysbiosis in inflammatory bowel disease. arthritis rheumatol 2015; 67(1):128-39. 2. song h, yoo y, hwang j, et al. faecalibacterium prausnitzii subspecies-level dysbiosis in the human gut microbiome underlying atopic dermatitis. j allergy clin immunol 2016; 137(3):852-60. 3. west ce, ryden p, lundin d, et al. gut microbiome and innate immune response patterns in ige-associated eczema. clin exp allergy 2015; 45(9):1419-29. 4. lee sy, yu j, ahn km, et al. additive effect between il-13 polymorphism and cesarean section delivery/prenatal antibiotics use on atopic dermatitis: a birth cohort study (cocoa). plos one 2014; 9(5):e96603. 5. williams mr, gallo rl. evidence that human skin microbiome dysbiosis promotes atopic dermatitis. j invest dermatol 2017; 137(12):2460-1. 6. mehta h, goulet po, mashiko s, et al. early-life antibiotic exposure causes intestinal dysbiosis and exacerbates skin and lung pathology in experimental systemic sclerosis. j invest dermatol 2017; 137(11):2316-25. 7. gopalakrishnan v, spencer cn, nezi l, et al. gut microbiome modulates response to anti-pd-1 immunotherapy in melanoma patients. science 2018; 359(6371):97-103. 8. sivan a, corrales l, hubert n, et al. commensal bifidobacterium promotes antitumor immunity and facilitates anti-pd-l1 efficacy. science 2015; 350(6264):1084-9. 9. vetizou m, pitt jm, daillere r, et al. anticancer immunotherapy by ctla-4 blockade relies on the gut microbiota. science 2015; 350(6264):107984. 10. dubin k, callahan mk, ren b, et al. intestinal microbiome analyses identify melanoma patients at risk for checkpoint-blockade-induced colitis. nat commun 2016; 7(10391. 11. routy b, le chatelier e, derosa l, et al. gut microbiome influences efficacy of pd-1-based immunotherapy against epithelial tumors. science 2018; 359(6371):91-7. 12. botticelli a, zizzari i, mazzuca f, et al. cross-talk between microbiota and immune fitness to steer and control response to anti pd-1/pdl-1 treatment. oncotarget 2017; 8(5):8890-9. 13. roy s, trinchieri g. microbiota: a key orchestrator of cancer therapy. nat rev cancer 2017; 17(5):271-85. 14. shi b, bangayan nj, curd e, et al. the skin microbiome is different in pediatric versus adult atopic dermatitis. j allergy clin immunol 2016; 138(4):1233-6. powerpoint presentation improved prognostic guidance by the 31-gene expression profile test for clinical decisions after a negative lymph node for patients with cutaneous melanoma background ›despite a good overall prognosis for patients with a negative slnb, 10-24% will experience recurrence or metastasis, and melanoma-specific survival (mss) rates range from 82-99%.1-4 a subset of these patients (stage iib-iic) are currently eligible for adjuvant therapy, though it is unclear which patients will benefit and which patients do not need therapy.5 ›the recent keynote-716 trial showed a benefit of adjuvant pembrolizumab in patients with stage iib-iic melanoma (9% rfs improvement), but 80% had an adverse event (16% grade 3 and higher), and 18% discontinued treatment due to adverse events.5 ›these data underpin a need for prognostic tools beyond clinicopathologic features to identify patients with high-risk tumor staging but low-risk tumor biology, or low-risk tumor staging but high-risk tumor biology, so that patients receive risk-aligned treatment.1-2 ›multiple prospective and independent studies have shown that the 31-gep test is a consistent and independent predictor of survival outcomes in large populations of patients with stage i-iii cm, and that clinicians use the 31-gep to guide patient management decisions.3, 6-10 acknowledgments & disclosures references ›sk, cb, bm, mg, rc, and kc are employees and shareholders of castle biosciences, inc. ›vp has no disclosures results presented at the winter clinical dermatology conferences 2023. brian martin phd1, christine bailey, mph1, matthew goldberg, md1,2, valentina petkov, md, mph3, robert cook, phd1, kyle covington, phd1, sarah kurley, phd1 1castle biosciences, inc., friendswood, tx 2icahn school of medicine at mount sinai, new york, ny, 3national cancer institute, surveillance research program, bethesda, md for more information: mgoldberg@castlebiosciences.com objective in collaboration with the national cancer institute’s surveillance, epidemiology, and end results (seer) program (covering 34% of the u.s. population during the study period) this study sought to: ›demonstrate the performance of the 31-gep to identify patients with high-risk tumor biology in an unselected, clinically tested cohort of patients with a negative lymph node. ›in patients with a negative lymph node, the 31-gep identifies patients more or less likely to die from their melanoma in the absence of adjuvant therapy, and the 31-gep is a significant predictor of melanoma-specific death, even when accounting for substage. ›the 31-gep can direct care to patients with high-risk tumor biology who are most likely to benefit from higher intensity management and away from those unlikely to benefit from adjuvant therapies to spare patients from adjuvant therapy-associated adverse events. conclusions ›seer cancer registries linked cm cases diagnosed from 2016-2018 to data for patients with cm who were tested with the 31-gep (n=3,271). linkage was mediated by information management services (an honest broker for the seer registries). a de-identified dataset was used for this analysis. a focused analysis of negative lymph node patients was performed. ›kaplan-meier analysis with the log-rank test was used to analyze 3-year melanoma-specific survival (mss). multivariable cox regression was used to identify factors associated with mss. scan or click here for more info methods 1. thomas, d. c. et al. ann surg oncol 26, 2254–2262 (2019). 2.jones, e. l. et al. jama surgery 148, 456–61 (2013). 3. greenhaw, et al. dermatol surg 44, 1494–1500 (2018). 4. o’connell, e. et al. mel research 26, 66-70 (2016). 5. luke et al. lancet, 399, 1718-1729 (2022) 6. hsueh, e. c. et al. jco precision oncology 5, 589–601 (2021). 7. vetto, j. t. et al. future oncology 15, 1207–1217 (2019). 8. podlipnik, s. et al. j eur acad dermatol venereol 33, 857–862 (2019). 9. dillon, l. d. et al. skin j cutaneous med 2, 111–121 (2018). 10. berger, a. c. et al. curr med res opin 32, 1599–1604 (2016). figure 1. using the 31-gep in patients with a negative lymph node identifies those at highest risk of dying from their disease. table 1. multivariable analysis demonstrates independent and significant prognostic information compared to traditional staging factors melanoma-specific survival multivariable hr (95% ci) 31-gep class 1a reference 31-gep class 1b/2a 5.76 (1.42-23.41) 31-gep class 2b 10.50 (2.55-43.28) age (continuous) 1.05 (1.02-1.08) ajcc stage ia reference ajcc stage ib 1.48 (0.37-6.01) ajcc stage iia 3.93 (1.10-14.12) ajcc iib 3.24 (0.82-12.86) ajcc iic 4.58 (1.09-19.22) clinical impact ›patients with class 1a results had higher 3-year mss (class 1a: 99.7%; class 1b/2a: 97.8%; class 2b: 91.8%, p<0.001). › in the subset of patients with iib-iic disease (n=311), no class 1a (0%, 0/38) patients died from melanoma compared with 6.7% (14/210; 8 iib, 6 iic) of class 2b patients. ›using the 31-gep results to guide increased clinical management and surveillance for patients at high risk of melanoma-specific death may improve patient outcomes. node neg class 1a class 1b-2b continue low intensity management consider increased intensity management, adjuvant therapy (stage iib, iic and iii) or clinical trials increased surveillance = early detection of metastasis (low tumor burden) demonstrated improved response to surgical and systemic therapy https://castlebiosciences.com/research-development/publications/ slide 1 skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 579 brief articles anti-sae1 antibodies and dermatomyositis: a case series of three patients claire wilson bs1*, brandon roman bs1*, kurt a. ashack md1, iris k. aronson md1 1department of dermatology, university of illinois at chicago college of medicine, chicago, il *co-first authors diagnosing clinically amyopathic dermatomyositis (cadm) is a challenge for clinicians due to the lack of classic muscle findings associated with dermatomyositis (dm) and the wide array of clinical presentations depending on the associated antibody subtype.1 in 2007, betteridge et al. described a new subtype of cadm associated with anti-small ubiquitin-like modifier activating enzyme 1(anti-sae1) antibodies.2 this subtype of cadm is often recalcitrant to treatment and may be associated with severe cutaneous disease, dysphagia, and interstitial lung disease.3 to date, few patients with anti-sae1 dm have been described, and usually in large descriptive cohort studies including all dm subtypes. thus, it is increasingly important to further describe this rare subtype to solidify cutaneous findings, associated symptoms, and potential therapeutic options. herein, we describe three patients with anti-sae1 dm, with one patient presenting with a previously undescribed cutaneous manifestation. case 1 a 56-year-old caucasian woman presented with two months of an erythematous and pruritic eruption on the scalp, face, neck, abstract to date, few patients with anti-sae1 dermatomyositis (dm) have been described, and usually in large descriptive cohort studies including all dm subtypes. thus, it is increasingly important to further describe this rare subtype to solidify cutaneous findings, associated symptoms, and potential therapeutic options. herein, this case series describes three patients with anti-sae1 dm with respect to their clinical and laboratory findings, and also their response to treatment. all three patients eventually presented with classic cutaneous manifestations of dermatomyositis, however, case 2 presented initially with cutaneous manifestations not described in the literature. furthermore, two patients presented with dysphagia, with case 2 experiencing a life-threatening dysphagia not typically described in the literature. two of three patients also presented with early signs of interstitial lung disease. lastly, cutaneous disease was only responsive to immunosuppressants in one patient. unfortunately, this observational case-series consisted of only three patients, limiting the generalizability of our results. however, this study provides further support of the recalcitrant nature of this dm subtype, and commonly affected extracutaneous systems including the gastrointestinal and pulmonary systems. larger studies of this patient population are needed to further confirm our associated findings. introduction case presentation skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 580 figure 1. case 1 clinical findings. cutaneous examination of case 1 revealed (a) confluent erythematous patches involving the upper arms bilaterally, (b) the upper chest, (c) and the upper back. the patient also had erythematous and edematous plaques involving the bilateral upper eyelids, and erythematous macules over the dorsal hands. trunk, and upper extremities (figure 1).at presentation, patient did not report any myalgias, weakness, dysphagia, dyspnea, or weight loss. over the next several months, patient developed muscle weakness and dysphagia, which responded to a combination of monthly intravenous immune globulin (ivig), mycophenolate mofetil (mmf), and prednisone. however, her cutaneous disease did not improve with the above treatments in addition or to intramuscular and topical corticosteroids and worsened with hydroxychloroquine, which was then discontinued. case 2 a 57-year-old african american woman presented with a 1.5 month history of lesions clinically consistent with discoid lupus erythematosus (dle) (figure 2). the patient denied myalgias, weakness, or dyspnea. hydroxychloroquine resolved her eroded dle-like lesions, with multiple areas of scarring left behind. three months later, she developed extensive violaceous, erythematous, and edematous macules, papules, patches, and plaques on the face, neck, chest, arms, dorsal hands, and lateral thighs consistent with a diagnosis of dermatomyositis. she was subsequently hospitalized due to severe dysphagia, which improved with intravenous methylprednisolone. methotrexate, oral corticosteroids, and topical corticosteroids were started in addition to hydroxychloroquine with no significant improvement in cutaneous manifestations. skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 581 figure 2. case 2 clinical findings. clinical exam of case 2 revealed (a) diffuse erythematous, jagged and eroded plaques of the trunk and upper and lower extremities bilaterally. the patient also had (b) erythematous and eroded plaques at different stages affecting the upper anterior legs and lateral thighs, and (c) erythematous and erosive papules and plaques overlying the dorsal hands. case 3 a 66-year-old woman presented with over a one-year history of a diffuse pruritic, burning erythematous eruption covering the face, trunk, upper extremities, and knees (figure 3). on presentation, patient reported no myalgias, dysphagia, dyspnea, or weight loss. however, over time, the patient developed generalized weakness, which improved (along with cutaneous findings) with topical and oral corticosteroids and mmf. histopathology for all three cases demonstrated a vacuolar interface dermatitis with stromal mucin deposition and nonspecific direct immunofluorescence findings. additionally, a dermatomyositis panel was positive for anti-sae1 antibodies for all three patients. table 1 further describes clinical and laboratory findings in our patients. similar to the majority of patients with sae antibody dm, our patients presented with skin disease prior to the development of other symptoms. presentation with dysphagia occurs less frequently, varying between 29% to 78% of initial presentations.3-5 the degree of dysphagia varies as well, but can be severe and life threatening as demonstrated by case 2. myositis typically develops several months after the onset of skin findings in this specific patient population, with elevated creatinine kinase (ck) levels being very common.3 elevated ck levels among these patients have been noted by peterson et al. (2/17 patients), muro et al. (7/7 patients), and ge et al. (6/11 patients).3-5 among the western cohorts studied by ge et al., the betteridge study found 2/2 and 9/11 patients with elevated ck, and the tarricone study found discussion a b c skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 582 figure 3. case 3 clinical findings. dermatological examination of case 3 revealed (a) erythematous patches covering the forehead, periocular area, cheeks, chest and arms, abdomen, and (b) back. there were also (c) erythematous papules on the dorsal hands in addition to ragged cuticles. (d) both knees also had erythematous to violaceous patches bilaterally. 4/5 patients with elevated ck. among the asian cohorts, the fujimoto study found 5/7 patients with elevated ck. 3within our small cohort, ck and aldolase levels were initially all within normal limits, however, ck levels became elevated in cases 1 and 2. case 3 did develop severe subjective weakness despite normal ck. furthermore, two of our three patients were ana positive, with one patient demonstrating anti-histone antibodies, and another with anti-ssdna antibodies, findings not described in the literature with respect to this specific subset of dm patients. two of the three patients developed ct findings consistent with interstitial lung disease, another commonly reported finding among this patient population. this report supports this complicating feature in antisae1 patients. to date, none of our patients have been diagnosed with a malignancy, which aligns with other studies.3 of our three patients, case 2 deviated the most from all reported cases with respect to cutaneous findings. though ulcerations have been reported in dermatomyositis, a case of diffuse eroded plaques has not been reported in the onset of dm in the literature. though her initial cutaneous ulcerations improved with hydroxychloroquine and prednisone, the diffuse poikilodermatous erythroderma that later developed did not. rituximab infusions have also not been beneficial for case 2. furthermore, case 3 showed very good response to the addition of mmf with oral steroids, with remarkable improvement in her cutaneous disease and muscular weakness. case 1 showed improvement in skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 583 table 1: summary of patient characteristics patient # 1 2 3 age 56 57 66 gender f f f dysphagia + + muscular weakness +a +a holster sign + + heliotrope sign + + + v sign + + gottron’s papules + + shawl sign + + skin ulceration + myalgia arthralgia pulmonary findings +b +c cancer family history of cancer +d +e +f ck/aldolaseg normal normal normal esr elevated elevated normal crp normal normal normal ana +h +i anti-histone + n/a n/a anti-ss dna + hcq use +j + ana – anti-nuclear antibody; hcq hydroxychloroquine a objective clinical weakness develops in cases 1 and 3 after having cutaneous manifestations alone for at least six months. b a chest ct with contrast showed bibasilar wedge-shaped consolidations suggesting interstitial lung disease (ild). c ct revealed tree in bud opacities in the left lower lung representing small airway disease. d family history for case 1 included two sisters with breast cancer. e family history for case 2 included breast cancer in one family member. f family history for case 3 included a mother with sarcoidosis and uterine cancer, and a cousin with breast cancer. g initial ck and aldolase levels were all normal h ana titer 1:640, speckled pattern. i ana titer 1:320, homogeneous pattern. j hydroxychloroquine (hcq) was discontinued due to cutaneous adverse reactions. her muscular weakness with ivig, but her cutaneous disease remains recalcitrant. overall, this small group of patients shows variable cutaneous response to treatment. finally, a majority of dm cases are considered idiopathic, but cases of medication induced dermatomyositis have been reported.6 it is important to note that two of our three patients were on statin medications prior to the development of skin disease. unfortunately, their disease persisted despite discontinuation of this medication, and statin involvement should be considered in each case of dm. limitations of this study include our small sample size of three patients. this limits the generalizability of our results. therefore, it is important that more case-series limited to this specific subtype be published to help identify clinical features and possible treatments. herein, we add three patients to the literature with this uncommon subtype of cadm. additionally, we demonstrate several key clinical and laboratory findings that deviate from the average phenotype of cadm patients with anti-sae1 antibodies. conflict of interest disclosures: none funding: none corresponding author: kurt a. ashack, md dermatology associates of west michigan 1740 east paris ave. se grand rapids, mi 49546 phone: 616-949-5600 fax: 616-949-6571 email: kurt.ashack@gmail.com conclusion skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 584 references: 1. bailey ee , fiorentino df. amyopathic dermatomyositis: definitions, diagnosis, and management. curr rheumatol rep 2014;16:465. 2. bodoki l, nagy-vincze m, griger z, betteridge z, szollosi l , danko k. four dermatomyositisspecific autoantibodies-anti-tif1gamma, antinxp2, anti-sae and anti-mda5-in adult and juvenile patients with idiopathic inflammatory myopathies in a hungarian cohort. autoimmun rev 2014;13:1211-9. 3. ge y, lu x, shu x, peng q , wang g. clinical characteristics of anti-sae antibodies in chinese patients with dermatomyositis in comparison with different patient cohorts. sci rep 2017;7:188. 4. muro y, sugiura k , akiyama m. low prevalence of anti-small ubiquitin-like modifier activating enzyme antibodies in dermatomyositis patients. autoimmunity 2013;46:279-84. 5. peterson lk, jaskowski td, la'ulu sl , tebo ae. antibodies to small ubiquitin-like modifier activating enzyme are associated with a diagnosis of dermatomyositis: results from an unselected cohort. immunol res 2018;66:431-6. 6. borges ibp, silva mg, misse rg , shinjo sk. lipid-lowering agent-triggered dermatomyositis and polymyositis: a case series and literature review. rheumatol int 2018;38:293-301. skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 279 brief articles treatment of recalcitrant prurigo nodularis with dupilumab matthew t. reynolds, mpas, pa-c1, scott m. dinehart, md1, katlyn r. anderson, mpas, pa-c1, joe gorelick, fnp-c2 1arkansas dermatology, little rock, ar 2california skin institute, san jose los gatos, ca prurigo nodularis (pn) is a condition characterized by aberrant and recalcitrant itching. patients scratch and pick at their pruritic skin which results in nodules that preferentially occur on the extensor aspects of the extremities and spare difficult to reach areas, like the upper-middle back. treatment with various topical and systemic therapies is often ineffective. many of the aggressive systemic therapies are also ineffective and associated with serious adverse events. we report four patients with recalcitrant pn who were treated successfully with dupilumab (dupixent) (table 1). all patients were treated with a standardized dose of dupilumab 600mg sc on day 1, then 300mg sc every other week thereafter. itch scores at weeks 0, introduction objectives: prurigo nodularis (pn) is a disease of aberrant and recalcitrant itching which is difficult to effectively manage. there are no current fda-approved therapies for pn. the current topical and systemic medications used for this condition provide less than optimal efficacy for the majority of patients with this condition and often have unacceptable side effects. we report 4 patients who were effectively treated with dupilumab (dupixent) for the treatment of recalcitrant pn. methods: four patients were treated successfully with dupilumab, a systemic biologic agent that is not immunosuppressive (dupixent; sanofi-regeneron). patients were treated with dupilumab monotherapy, without the use of other systemic immunosuppressing agents. the peak pruritus numerical rating scale (nrsi) was used to evaluate patients at weeks 0 and 4. results: dupilumab therapy results in a dramatic reduction in nrsi scores by week 4 and that result continues throughout the duration of therapy. this reduction in itch is seen with continuous therapy. conclusion: dupilumab therapy appears effective in reducing the overall itch severity in patients with pn. the usage of dupilumab as a monotherapy shows promise in the treatment of pn. the therapeutic response to dupilumab seen in pn suggests that the pathogenesis of pn may overlap with that of atopic dermatitis. abstract skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 280 4, and current were calculated according to the pruritis numerical rating scale (nrsi). case 1 a 65-year-old woman with a five-year history of pn had an nrsi score of 10/10 prior to treatment with dupilumab. previous therapies included pimecrolimus, clobetasol, prednisone, cetirizine, and loratadine. nrsi scores at weeks 0, 4, and current were as follows: 10, 2 and 0, respectively, for a total treatment length of 14 months. currently, she is on dupilumab 300mg sc every other week and clobetasol ointment intermittently. case 2 a 17-year-old woman with a 15-year history of pn and nrsi score of 10/10 prior to starting dupilumab therapy. previous therapies included topical clobetasol, il kenalog, hydroxyzine, unna boot wraps, bactrim ds, and prednisone. nrsi scores at weeks 0, 4, and current were as follows: 10, 2, and 1 for a total treatment length of 11 months. currently, crisaborole and hydrocortisone lotion are used with dupilumab. case 3 a 46-year-old male with pn for six years and a baseline nrsi score of 10/10 was treated with dupilumab. previous therapies: clobetasol, im/il kenalog, prednisone, and pimecrolimus. after 13 months of therapy, the patient’s nrsi scores have reduced from 10 at week 0, 0 at week 4, with a current nrsi score of 0. he has been using clobetasol ointment intermittently in conjunction with his dupilumab injections. case 4 a 71-year-old woman with pn for > 4 years recorded a baseline nrsi score of 10/10. (figure 1). previous treatments include topical corticosteroids, il kenalog, pimecrolimus, crisaborole, doxycycline, methotrexate, and gabapentin. the patient’s nrsi scores have trended downward while on dupilumab from a score of 10 at week 0 to a score of 3 at week 4, respectively. currently, her nrsi score is 1 at 16 months of therapy. she has been using calamine lotion, sarna lotion, and ice packs concomitantly with dupilumab therapy. known risk factors for pn development include chronic atopic dermatitis, psychiatric factors, and underlying systemic disorders such as malignancies, renal failure, liver failure, and hiv infection. 1, 2 currently, pn is categorized as a neurodermatitis despite having a pathogenesis that remains mostly unknown. of note, interleukin (il)-4 and 31 are upregulated in the lesional skin of pn patients.3, 4 additionally, atopic dermatitis (ad), a t-helper (th) 2 cell-mediated disease, demonstrates increased expression of il-4, 13, and the il-31 receptor α-chain (il31ra). 5 to date, numerous therapies are used to treat pn. phototherapy with ultraviolet light (uv), psoralen plus ultraviolet a light (puva), ultraviolet a (uva) light alone, and ultraviolet b light (uvb) alone as well as gabapentin reportedly have anecdotal efficacy.6, 7 more aggressive immunomodulatory agents are often utilized: oral glucocorticoids, thalidomide, methotrexate (mtx), and cyclosporine, however, these therapies are often fraught with potentially detrimental side effects. recently, reports of pn patients treated with alternative non-fda indicated agents, namely dupilumab (dupixent) have gained attention. a case series of three patients with generalized pn were treated with standard cases discussion skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 281 table 1. four patients with pn treated with dupilumab. age disease duration previous therapies pathology results concomitant therapies nrsi score length of duplimab treatment 46 6 years topical steroids, im/il kenalog, prednisone, pimecrolimus lsc clobetasol ointment week 0: 10 week 4: 0 current: 0 13 months 17 15 years topical steroids, il kenalog, hydroxyzine, prednisone 2013: prurigo nodularis 2018: spongiotic dermatitis tac, crisaborole week 0: 10 week 4: 3 current: 1 11 months 65 5 years pimecrolimus, topical steroids, prednisone, cetirizine, loratadine spongiotic and psoriasiform dermatitis patch testing: + mdbgn + irritant: balsam of peru -ses. lactone mix propylene glycol clobetasol ointment week 0: 10 week 4: 2 current: 0 14 months 71 4 years topical steroids, il kenalog, pimecrolimus, crisaborole, doxycycline, methotrexate, gabapentin prurigo nodularis shave biopsy: scc (arising from pn areas) calamine, sarna, cold packs week 0: 10 week 4: 3 current: 1 16 months figure 1. patient 4 before dupilumab initiation (a) and at 3 months (b). skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 282 atopic dermatitis dosing (initially 600 mg, then 300 mg every two weeks). patients were treated with concomitant systemic and topical therapies along with dupilumab. overall itching was rated on a scale of 0 to 10 per the pruritis numerical scale (nrsi). the average disease duration for these patients was 8.6 years. two patients were on concomitant thalidomide and cyclosporine in addition to dupilumab therapy. pruritis scores were measured on weeks 0, 4, 8, and 12 , with results seen as early as week 4. by week 12, all participants remained on dupilumab with an average pruritis nrsi score of 1.8 mollanazar et al. also described four patients treated with dupilumab for pn. all patients had a trial period of 15 mg of mirtazapine, super-potent topical steroids, and a calcineurin inhibitor ointment before treatment with dupilumab. pruritis was also measured according to the nrsi scale. the average nrsi score was 8.75 at week 0 and all patients ultimately reached an nrs itch score of 0 by the end of 8 weeks. interestingly, three patients reported an nrsi score of 0 by week 4.9 we describe four patients with recalcitrant pn treated successfully with a dupilumab (dupixent). our patients had all received intensive topical and systemic treatments, which were mostly ineffective prior to initiation with dupilumab. in contrast to other cases reported, our patients were treated with a single systemic agent, dupilumab. our patients used a variety of topical medications as adjunctive therapy. it appears that dupilumab can be effective monotherapy in patients with pn. dupilumab, a fully-humanized monoclonal igg antibody that blocks the receptor site on type 1 and type 2 receptors for interleukin-4 alpha, blocks both the il-4 and il-13 signaling pathways. activation of the th2 pathway has often been thought to play a role in the development of pn lesions.10 since dupilumab effectively blocks several key components of this pathway, there may be a possible, previously undescribed, inflammatory process in pn, similar to ad that warrants further investigation. in our subset of patients, patch testing was performed to reduce the potential of multicausality for the development of pn. previously, boonstra et al., described patients with atopic dermatitis whom appear to have a higher rate of contact allergen sensitization. although contact dermatitis is primarily mediated by the th1 pathway, there has been evidence to suggest the allergens can induce th2 cell-mediated signaling pathways.11 conflict of interest disclosures: reynolds – consultant sanofi/regeneron, lilly pharmaceuticals, abbvie, novartis, castle biosciences, sun, primus; speaker sanofi/regeneron, novartis dinehart – speaker regeneron; consultant and speaker, genentech gorelick – consultant sanofi/regeneron; consultant and speaker dermira; consultant and speaker lilly pharmaceuticals; speaker pfizer anderson – no conflicts of interest funding: none corresponding author: matthew t. reynolds, pa-c arkansas dermatology 4261 stockton drive, suite 200 north little rock, ar 72117 email: mreynolds@arkansasdermatology.com references: 1. stander s, stumpf a, osada n, wilp s, chatzigeorgakidis e, pfleiderer b. gender differences in chronic pruritus: women present different morbidity, more scratch lesions and higher burden. br j dermatol. 2013;168:12731280. 2. winhoven sm, gawkrodger dj. nodular prurigo: metabolic diseases are a common association. clin exp dermatol. 2007; 32:224-225. mailto:mreynolds@arkansasdermatology.com skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 283 3. sonkoly e, muller a, lauerma ai, et al. il-31: a new link between t cells and pruritus in atopic skin inflammation. j allergy clin immunol. 2006;117:411-417. 4. park k, mori t, nakamura m, tokura y. increased expression of mrnas for il-4, il-17, il-22 and il-31 in skin lesions of subacute and chronic forms of prurigo. eur j dermatol. 2011; 21:135-136. 5. nakashima c, otsuka a, kabashima k. interleukin-31 and interleukin-31 receptor: new therapeutic targets for atopic dermatitis. exp dermatol. 2018 apr;27(4):327-331. 6. bruni e, caccialanza m, piccinno r. phototherapy of generalized prurigo nodularis. clin exp dermatol. 2009;35:549-550. 7. gencoglan g, inanir i, gunduz k. therapeutic hotline: treatment of prurigo nodularis and lichen simplex chronicus with gabapentin. dermatol ther. 2010;23:194-198. 8. beck, k., yang, e., sekhon, s., bhutani, t., liao, w. dupilumab treatment for generalized prurigo nodularis. jama dermatology. 2019; 155:118120. 9. mollanazar, n., elgash, m., weaver, l., valdesrodriquez, r., hsu, s. reduced itch associated with dupilumab treatment in 4 patients with prurigo nodularis. jama dermatology. 2019; 155:121-122. 10. beck, la., et.al. dupilumab treatment in adults with moderate-to-severe atopic dermatitis. n engl j med. 2014; 37(2):130-139. 11. boonstra m, rustemeyer t, middelkamp-hup ma. both children and adult patients with difficultto-treat atopic dermatitis have high prevalences of concomitant allergic contact dermatitis and are frequently polysensitized. j eur acad dermatol venereol. 2018 sep;32(9):1554-1561. https://www.ncbi.nlm.nih.gov/pubmed/?term=nakashima%20c%5bauthor%5d&cauthor=true&cauthor_uid=29524262 https://www.ncbi.nlm.nih.gov/pubmed/?term=otsuka%20a%5bauthor%5d&cauthor=true&cauthor_uid=29524262 https://www.ncbi.nlm.nih.gov/pubmed/?term=kabashima%20k%5bauthor%5d&cauthor=true&cauthor_uid=29524262 https://www.ncbi.nlm.nih.gov/pubmed/29524262 https://www.ncbi.nlm.nih.gov/pubmed/29524262 https://www.ncbi.nlm.nih.gov/pubmed/?term=boonstra%20m%5bauthor%5d&cauthor=true&cauthor_uid=29578626 https://www.ncbi.nlm.nih.gov/pubmed/?term=rustemeyer%20t%5bauthor%5d&cauthor=true&cauthor_uid=29578626 https://www.ncbi.nlm.nih.gov/pubmed/?term=middelkamp-hup%20ma%5bauthor%5d&cauthor=true&cauthor_uid=29578626 https://www.ncbi.nlm.nih.gov/pubmed/?term=middelkamp-hup%20ma%5bauthor%5d&cauthor=true&cauthor_uid=29578626 https://www.ncbi.nlm.nih.gov/pubmed/29578626 https://www.ncbi.nlm.nih.gov/pubmed/29578626 biochemistry laboratory shift based on common terminology criteria in patients with advanced basal cell carcinoma receiving sonidegib 200 mg daily: results from the 42-month bolt study alexander guminski1,2, peter foley3,4,5, jean-jacques grob6, caroline robert7, ralf gutzmer8, nicholas squittieri9, felix kiecker10 1royal north shore hospital, sydney, australia; 2the university of sydney, sydney, australia; 3department of dermatology, st vincent’s hospital melbourne, fitzroy, victoria, australia; 4the university of melbourne, parkville, victoria, australia; 5skin health institute inc., carlton, victoria, australia; 6department of dermatology and oncology, university of aix-marseille, timone hospital, marseille, france; 7department of dermatology, institut gustave roussy and paris-saclay university, villejuif, france; 8university clinic for dermatology, venereology, allergology and phlebology, johannes wesling clinic minden, minden, germany; 9sun pharmaceutical industries, inc., princeton, nj, usa; 10department of dermatology, venereology, and allergology, charité universitätsmedizin berlin, edmund-lesser-haus, berlin, germany background • hedgehog inhibitors were developed to block aberrant hedgehog signaling found in most sporadic basal cell carcinomas (bccs); inhibition of the hedgehog pathway is among the limited treatment options available for patients with advanced bcc1,2 • sonidegib is a hedgehog inhibitor that selectively targets smoothened3 and is approved in the us, the eu, switzerland, and australia for the treatment of adult patients with locally advanced bcc (labcc) not amenable to curative surgery or radiation therapy3–6 — sonidegib is also approved to treat metastatic bcc (mbcc) in switzerland and australia5,6 • through 42 months of the phase 2 bolt (basal cell carcinoma outcomes with lde225 [sonidegib] treatment trial (nct01327053), sonidegib 200 mg daily demonstrated durable efficacy and consistent/ manageable toxicity7–10 • evaluation of clinical biochemistry in patients with advanced bcc provides valuable information on the tolerability and safety of sonidegib objective • to characterize changes in biochemistry laboratory values in patients receiving sonidegib 200 mg daily through 42 months of treatment for advanced bcc methods study design • bolt was a randomized, double-blind, phase 2 clinical trial conducted in 58 centers across 12 countries10 • eligible patients had histologically confirmed labcc or mbcc and were randomized 1:2 to receive sonidegib 200 or 800 mg orally daily, respectively (figure 1) figure 1. bolt study design patient population* • labcc (aggressive and nonaggressive) • mbcc sonidegib 200 mg daily treatment sonidegib 800 mg daily stratification† randomization (1:2) treatment was continued until disease progression, unacceptable toxicity, death, study termination, or withdrawal of consent follow-up (after treatment discontinuation) • tumor response q8w during year 1 and then q12w until progression • subsequent anticancer therapy • aes until 30 days after last dose of sonidegib • survival follow-up q12w until death, lost to follow-up, or withdrawn consent (and at time of final analysis) *patients previously treated with sonidegib or other hhi were excluded. †stratification was based on stage, disease histology for patients with labcc (nonaggressive vs aggressive), and geographic region. ae, adverse event; bcc, basal cell carcinoma; bolt, basal cell carcinoma outcomes with lde225 (sonidegib) treatment; hhi, hedgehog inhibitor; labcc, locally advanced bcc; mbcc, metastatic bcc; q8w, every 8 weeks; q12w, every 12 weeks. assessments • the primary efficacy endpoint was objective response rate (orr) per central review (figure 2) • orr was defined as the proportion of patients with a confirmed best overall response (determined based on consecutive assessments ≥4 weeks apart) of complete response or partial response figure 2. bolt study endpoints •os •safety •orr and dor per investigator review •pfs and ttr per central review other secondary dor and cr rates per central review according to mrecist (labcc) or recist v1.1 (mbcc) key secondary orr  best overall confirmed response of cr or pr per central review according to mrecist (labcc) or recist v1.1 (mbcc) primary bcc, basal cell carcinoma; bolt, basal cell carcinoma outcomes with lde225 (sonidegib) treatment; cr, complete response; dor, duration of response; labcc, locally advanced bcc; mbcc, metastatic bcc; mrecist, modified recist; orr, objective response rate; os, overall survival; pfs, progressionfree survival; pr, partial response; recist, response evaluation criteria in solid tumors; ttr, time to tumor response. • tumor response was evaluated by central review using modified response evaluation criteria in solid tumors (mrecist) for patients with labcc and recist v1.1 for patients with mbcc biochemistry assessments • clinical biochemistry assessments were ideally performed in fasted patients at screening, biweekly for 14 weeks, then every 4 weeks until week 77, and then as clinically indicated until end of treatment — assessments included alanine aminotransferase (alt), albumin, alkaline phosphatase, amylase, aspartate aminotransferase (ast), total bilirubin, total calcium, cholesterol, plasma and serum creatine kinase (ck), creatinine, glucose, lipase, magnesium, phosphorus, potassium, and sodium • biochemistry evaluations were performed by a central laboratory until week 182; after this, assessments were conducted locally • abnormal laboratory values constituted adverse events (aes) if they fulfilled ≥1 of the following criteria: — induced clinical signs or symptoms — considered clinically significant — required concomitant therapy or procedures — required changes in study treatment safety assessments • safety assessments included ae monitoring and recording until 30 days after the last dose through regular monitoring of hematology, clinical chemistry, electrocardiograms, vital signs, and physical condition — aes were coded using the medical dictionary for regulatory activities terminology v19.0, and toxicity was assessed using the national cancer institute common terminology criteria for adverse events v4.0311 results patient demographics and baseline disease characteristics • at baseline, 48 (60.8%) patients receiving sonidegib 200 mg daily (n = 79) were male; the median age of patients in this study was 67 years (table 1) table 1. baseline demographics and disease characteristics in patients receiving sonidegib 200 mg daily sonidegib 200 mg (n = 79) age, years, mean (sd) 65.6 (15.7) age, years, median (range) 67 (25–92) sex, male 48 (60.8) ecog performance status 0 50 (63.3) 1 19 (24.1) 2 8 (10.1) unknown 2 (2.5) stage labcc 66 (83.5) mbcc 13 (16.5) histologic/cytologic subtype aggressive* 40 (50.6) nonaggressive† 38 (48.1) undetermined 1 (1.3) number of lesions 0 0 1 30 (38.0) ≥2 49 (62.0) metastasis 14 (17.7) metastatic site lung 10 (12.7) lymph nodes‡ 1 (1.3) bone 2 (2.5) other§ 4 (5.1) prior antineoplastic therapy surgery 59 (74.7) radiotherapy 19 (24.1) data presented as n (%) unless otherwise indicated. *includes micronodular, infiltrative, multifocal, basosquamous, and sclerosing histological subtypes. †includes nodular and superficial histological subtypes. ‡includes axillary, parotid, submandibular, supraclavicular, and other. §includes trunk, brain, head, liver, neck, and upper extremities. bcc, basal cell carcinoma; ecog, eastern cooperative oncology group; labcc, locally advanced bcc; mbcc, metastatic bcc; sd, standard deviation. • at 42 months, orrs (95% confidence interval) in patients with labcc (n = 66) and mbcc (n = 13) receiving sonidegib 200 mg were 56.1% (43.3%–68.3%) and 7.7% (0.2%–36.0%), respectively; disease control rate (summed complete response, partial response, and stable disease rates) exceeded 90% in all patients biochemistry assessments • through 42 months of treatment with sonidegib 200 mg, most biochemistry laboratory values had shifts ≤grade 2, with the majority being ≤grade 1 (figure 3) • observed grade 3 shifts included elevations in alt, amylase, ast, bilirubin, plasma ck, serum ck, glucose, lipase, and potassium; 1 patient developed hyponatremia (table 2) • grade 4 shifts were minimal and included elevations in ast, serum ck, and lipase (table 2) figure 3a. distribution of biochemistry shifts for enzyme, protein, and lipid parameters in patients receiving sonidegib 200 mg daily* alt ast alp albumin amylase bilirubin cholesterol serum ck‡ creatinine lipase 0 20 40 60 80 100 p at ie nt s, % † wnl grade 1 grade 2 grade 3 grade 4 7.6 79.7 16.5 3.8 94.9 79.7 19.0 83.5 11.4 3.8 79.7 16.5 91.1 6.3 29.1 62.0 8.9 39.2 43.0 10.1 5.1 89.9 55.7 22.8 8.9 11.4 *n = 79. †values <3.8% are not shown within corresponding bars. ‡values for plasma ck were not included, as 86.1% of data values were missing for this parameter. alp, alkaline phosphatase; alt, alanine aminotransferase; ast, aspartate aminotransferase; ck, creatine kinase; wnl, within normal limits. figure 3b. distribution of biochemistry shifts for glucose and electrolyte parameters in patients receiving sonidegib 200 mg daily* wnl grade 1 grade 2 grade 3 grade 4 hyper hypo hyper hypo hyper hypo hyper hypo hyper hypo phosphatecalciumglucose magnesium potassium sodium 77.2 22.8 82.3 16.5 49.4 39.2 7.6 78.5 20.3 98.7 69.6 30.4 81.0 6.3 12.7 82.3 13.9 3.8 94.9 5.1 83.5 12.7 3.8 91.1 7.6 3.8 hypo 0 20 40 60 80 100 p at ie nt s, % † *n = 79. †values <3.8% are not shown within corresponding bars. wnl, within normal limits. table 2. distribution of biochemistry shifts for parameters with grade 3 or 4 shifts in patients receiving sonidegib 200 mg daily* within normal limits grade 1 grade 2 grade 3 grade 4 alt 63 (79.7) 13 (16.5) 0 3 (3.8) 0 amylase 66 (83.5) 9 (11.4) 3 (3.8) 1 (1.3) 0 ast 63 (79.7) 13 (16.5) 0 2 (2.5) 1 (1.3) bilirubin 72 (91.1) 5 (6.3) 1 (1.3) 1 (1.3) 0 plasma ck 8 (10.1) 1 (1.3) 1 (1.3) 1 (1.3) 0 serum ck 31 (39.2) 34 (43.0) 8 (10.1) 4 (5.1) 2 (2.5) hyperglycemia 39 (49.4) 31 (39.2) 6 (7.6) 3 (3.8) 0 lipase 44 (55.7) 18 (22.8) 7 (8.9) 9 (11.4) 1 (1.3) hyperkalemia 65 (82.3) 0 11 (13.9) 3 (3.8) 0 hyponatremia 72 (91.1) 6 (7.6) 0 1 (1.3) 0 all data presented as n (%). *n = 79. alt, alanine aminotransferase; ast, aspartate aminotransferase; ck, creatine kinase. safety and tolerability at 42 months • the majority of aes were grade 1–2 in severity • the most common all-grade aes in patients receiving sonidegib 200 mg daily were muscle spasms (54.4%), alopecia (49.4%), and dysgeusia (44.3%; figure 4) figure 4. adverse events reported in ≥20% of patients receiving sonidegib 200 mg daily percent of patients diarrhea fatigue nausea dysgeusia alopecia muscle spasm decreased appetite ck increased weight decreased 0 20 40 60 22.8 30.4 30.4 31.6 32.9 39.2 44.3 49.4 54.4 21.5 24.1 25.3 30.4 31.6 38.0 44.3 49.4 51.9 grade 1–2 grade 3–4 ck, creatine kinase. conclusions • through 42 months of treatment with sonidegib 200 mg daily, most patients experienced no biochemistry changes or grade 1 biochemistry shifts • overall safety findings at 42 months were consistent with observations at 30 months9 references 1. cortes je, et al. cancer treat rev. 2019;76:41–50. 2. kim jys, et al. j am acad dermatol. 2018;78(3):540–59. 3. odomzo (sonidegib capsules). full prescribing information. sun pharmaceutical industries, inc., cranbury, nj, usa. 4. european medicines agency. summary of product characteristics, wc500188762. http://www. ema.europa.eu/docs/en_gb/document_library/epar_-_product_information/human/002839/wc500192970. pdf. 5. swissmedic, authorization number 65065, 2015. https://www.swissmedic.ch/swissmedic/de/home/ humanarzneimittel/authorisations/new-medicines/odomzo--200mg--kapseln--sonidegibum-.html. 6. australian government department of health, artg 292262. https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/ pdf?openagent&id=cp-2017-pi-02511-1&d=2018030216114622483. 7. dummer r, et al. br j dermatol. 2020;182(6):1369–78. 8. dummer r, et al. j am acad dermatol. 2016;75(1):113–25.e115. 9. lear jt, et al. j eur acad dermatol venereol. 2018;32(3):372–81. 10. migden mr, et al. lancet oncol. 2015;16(6):716–28. 11. health udo, services h. common terminology criteria for adverse events (ctcae) version 4.0. national institutes of health, national cancer institute. 2009;4(03). acknowledgements medical writing and editorial support were provided by alex milliken, phd, of alphabiocom, llc, and funded by sun pharma. disclosures ag participated in advisory boards for bristol-myers squibb, pfizer, and sanofi; received honoraria from novartis; and received travel support from astellas, bristol-myers squibb, and sun pharma. pf participated in clinical trials (investigator), served on an advisory board, served as a consultant, received speaker’s bureau fees/honoraria, and/or received research and/or travel grants from abbvie, akaal, amgen, arcutis, aslan, astrazeneca, bristolmyers squibb, boehringer ingelheim, botanix, celgene, celtaxsys, csl, cutanea, dermira, eli lilly, galderma, geneseq, genetech, gsk, hexima, janssen, leo, mayne pharma, medimmune, merck; novartis, pfizer, regeneron pharmaceuticals, inc., reistone, roche, sanofi, sun pharma, ucb pharma, and valeant. j-jg has received personal fees from amgen, bristol-myers squibb, merck/pfizer, merck sharp & dohme, novartis, pierre fabre, and roche. cr has received consulting fees from amgen, bristol-myers squibb, merck sharp & dohme, novartis, pierre fabre, roche, and sanofi. rg serves as consultant to almirall, amgen, bristol-myers squibb, merck serono, merck sharp & dohme, novartis, pfizer, pierre fabre, roche, sanofi genzyme, sun pharma, and 4sc; has received travel grants and honoraria for lectures from almirall, amgen, bristol-myers squibb, merck serono, merck sharp & dohme, novartis, pierre fabre, roche, and sun pharma; and has received research funding from amgen, johnson & johnson, merck serono, and novartis. ns is an employee of sun pharmaceutical industries, inc. fk reports grants and personal fees from amgen, bristol-myers squibb, merck sharp & dohme, novartis, pierre fabre, roche, and sanofi. presented at the 5th annual 2020 pa & np fall clinical dermatology conference, orlando, florida, november 13–15, 2020 previously presented at winter clinical dermatology conference, hawaii, 2020 long-term safety of certolizumab pegol in plaque psoriasis: pooled analysis over 3 years from three phase 3, randomized, placebo-controlled studies a. blauvelt,1 c. paul,2 p. van de kerkhof,3 r. b. warren,4 a. b. gottlieb,5 r. g. langley,6 f. brock,7 c. arendt,8 m. boehnlein,9 m. lebwohl,5 k. reich10,11 1oregon medical research center, portland, or, usa; 2paul sabatier university, toulouse, france; 3radboud university, nijmegen, the netherlands; 4dermatology centre, salford royal nhs foundation trust, manchester nihr biomedical research centre, the university of manchester, uk; 5icahn school of medicine at mount sinai, new york, ny, usa; 6dalhousie university, nova scotia, canada; 7ucb pharma, slough, uk; 8ucb pharma, brussels, belgium; 9ucb pharma, monheim am rhein, germany; 10centre for translational research in inflammatory skin diseases, institute for health services research in dermatology and nursing, university medical center hamburg-eppendorf, germany; 11skinflammation® center, hamburg, germany references 1. certolizumab pegol prescribing information. available at www.accessdata.fda.gov/scripts/cder/daf/index. cfm; 2. certolizumab pegol summary of product characteristics. available at www.ema.europa.eu/en/ medicines/human/epar/cimzia-0; 3. blauvelt a et al. jeadv 2019;33(suppl 3):21–2; 4. gisondi p et al. int j mol sci 2017;18:2427. author contributions substantial contributions to study conception/design, or acquisition/analysis/interpretation of data: ab, cp, pvdk, rbw, abg, rgl, fb, ca, mb, ml, kr; drafting of the publication, or revising it critically for important intellectual content: ab, cp, pvdk, rbw, abg, rgl, fb, ca, mb, ml, kr; final approval of the publication: ab, cp, pvdk, rbw, abg, rgl, fb, ca, mb, ml, kr. author disclosures ab: abbvie, aclaris, akros, allergan, almirall, amgen, athenex, boehringer ingelheim, bristol-myers squibb, dermavant, dermira inc., eli lilly, flx bio, forte, galderma, janssen, leo pharma, novartis, ortho, pfizer, regeneron, sandoz, sanofi genzyme, sun pharma, ucb pharma; cp: abbvie, almirall, amgen, boehringer ingelheim, bristol-myers squibb, celgene, dermira inc., eli lilly, gsk, janssen, leo pharma, merck sharp & dohme, novartis, pierre fabre, pfizer, regeneron, sandoz, sanofi genzyme, ucb pharma; pvdk: abbvie, almirall, amgen, bristol-myers squibb, celgene, dermavant, eli lilly, janssen, leo pharma, novartis; rbw: abbvie, almirall, amgen, arena pharmaceuticals, avillion, boehringer ingelheim, celgene, eli lilly, janssen, leo pharma, novartis, pfizer, sanofi, ucb pharma, xenoport; abg: abbvie, allergan, avotres therapeutics, beiersdorf, boehringer ingelheim, bristol-myers squibb, celgene, dermira inc., dr. reddy’s laboratories, eli lilly, incyte, janssen, leo pharma, novartis, sun pharma, ucb pharma, valeant, xbiotech (no personal compensation); rgl: abbvie, amgen, boehringer ingelheim, celgene, centocor, eli lilly, janssen, leo pharma, novartis, pfizer, ucb pharma, valeant; fb, ca, mb: employees of ucb pharma; ml: allergan, aqua, leo pharma, promius; employee of mount sinai which received funds from: abbvie, amgen, boehringer ingelheim, celgene, eli lilly, janssen/johnson & johnson, kadmon, medimmune/astrazeneca, novartis, pfizer, valeant, vidac; kr: abbvie, affibody, amgen, biogen, boehringer ingelheim, celgene, centocor, covagen, forward pharma, gsk, janssencilag, kyowa kirin, leo pharma, eli lilly, medac, merck sharp & dohme, novartis, ocean pharma, pfizer, regeneron, samsung bioepis, sanofi, takeda, ucb pharma, valeant, xenoport. acknowledgments the studies were funded by dermira inc. in collaboration with ucb pharma. ucb is the regulatory sponsor of certolizumab pegol in psoriasis. we thank the patients and their caregivers in addition to the investigators and their teams who contributed to these studies. the authors acknowledge susanne wiegratz, ucb pharma, monheim am rhein, germany for publication coordination, sarah kavanagh, mph, of ucb pharma, raleigh, nc, usa for statistical analysis, and joe dixon, phd, costello medical, cambridge, uk for medical writing and editorial assistance. all costs associated with development of this poster were funded by ucb pharma. richard warren is supported by the manchester nihr biomedical research centre. objective • to report cumulative three-year safety data from three phase 3 trials of certolizumab pegol in plaque psoriasis. background • certolizumab pegol (czp) is an fc-free, pegylated, anti-tumor necrosis factor (tnf) biologic, which has been approved by the fda and ema for moderate to severe plaque psoriasis (pso).1,2 • czp has shown a safety profile consistent with the anti-tnf class in adults with pso over 96 weeks in phase 3 trials.3 • given that pso is a chronic disease that can require management over much of a patient’s lifetime, it is important to establish the long-term safety profile of treatments.4 • here, we report cumulative safety data, pooled from three czp in pso phase 3 trials over 144 weeks, from a total of 995 patients. methods patients and study design • pooled safety data are presented for patients who received ≥1 dose of czp during the 144 weeks of the cimpasi-1 (nct02326298), cimpasi-2 (nct02326272), or cimpact (nct02346240) phase 3 studies (figure 1). • only 11 placebo-randomized patients continued on placebo after week 16; placebo data are presented to week 16 only. • patient inclusion criteria: – ≥18 years of age with pso for ≥6 months; – psoriasis area and severity index (pasi) ≥12; – ≥10% body surface area (bsa) affected; – physician’s global assessment (pga) ≥3 on a 5-point scale; – candidates for systemic pso therapy, phototherapy and/or photochemotherapy. • exclusion criteria: previous treatment with czp or >2 biologics; previous treatment with etanercept (etn) (cimpact only); treatment with etn within the first 12 weeks of enrolment (cimpasi-1 and cimpasi-2 only); history of primary failure to any biologic or secondary failure to >1 biologic; erythrodermic, guttate or generalized pso types; history of or current, chronic or recurrent viral, bacterial or fungal infections. safety assessments • safety data were analyzed for the dose-combined czptreated group (all czp) and separately for each czp dose. • for patients exposed to both doses of czp over the course of the studies, treatment-emergent adverse events (teaes) were assigned to the dose being received at the time of onset, but each patient was counted in the ‘all czp’ group only once. • teaes and serious teaes were classified using meddra version 18.1. • serious teaes were defined as those meeting one or more of the following criteria: life-threatening, leading to death, hospitalization, congenital anomalies/birth defects, medically significant (based upon medical judgement), infections requiring intravenous antibiotics, or leading to persistent or significant disability. • incidence rates (ir) were calculated as the number of new cases per 100 patient-years (py). conclusions • no new safety signals were identified compared to previous studies in czp. • the risk of teaes did not increase with longer or higher czp exposure. • the safety profiles of the two czp doses were similar. figure 1. cimpasi-1, cimpasi-2, and cimpact study designs dose adjustments were permitted during the open-label periods of all three studies, and were either mandatory or at the discretion of the investigator. data collected during treatment with czp 400 mg q4w in cimpact were summarized under the czp 200 mg q2w treatment group. aloading dose of czp 400 mg q2w at weeks 0, 2 and 4 or weeks 16, 18, and 20. bw: twice per week; czp: certolizumab pegol; etn: etanercept; ld: loading dose; pasi: psoriasis area severity index; q2w: every two weeks; q4w: every four weeks. results patient population • across all three studies, a total of 995 patients received ≥1 dose czp through weeks 0–144. • baseline characteristics were well balanced between the two treatment groups (table 1). incidence of teaes • at week 144, the ir of teaes and serious teaes was comparable between czp dose groups (table 2). • the most common teaes, reported in ≥10% of patients, were nasopharyngitis (ir: 14.2; 95% ci: 12.5, 16.0) and upper respiratory tract infection (ir: 7.9; 95% ci: 6.7, 9.3). • the ir of teaes for czp-treated patients did not increase with longer exposure (table 3). selected teaes and serious teaes of interest • at week 144 the overall incidences of selected teaes of interest and serious teaes of interest were low and comparable between dose groups (table 4). • there were 7 deaths, 2 of which were assessed by the investigator as related to the study drug (table 2). • the irs of serious infections and malignancies were low, and were comparable between dose groups (table 4). • there was 1 case of active tuberculosis (tb) in a patient who lived in a country with a high tb prevalence (table 4). • there were no reports of serious skin disorders or hypersensitivity reactions, and no cases of lupus or lupus-like events. table 1. pooled demographics and baseline characteristics for patients who received ≥1 dose czp through weeks 0–144 apatients who received both czp 200 mg q2w and czp 400 mg q2w are only included once in the population count for the ‘all czp’ group; bczp 200 mg q2w patients received a loading dose of czp 400 mg at weeks 0, 2, and 4 or weeks 16, 18, and 20. bmi: body mass index; czp: certolizumab pegol; il: interleukin; pasi: psoriasis area severity index; pso: psoriasis; q2w: every two weeks; sd: standard deviation; tnf: tumor necrosis factor. all czpa (n=995) czp 400 mg q2w (n=728) czp 200 mg q2wb (n=731) baseline demographics and disease characteristics age, years, mean ± sd 45.6 ± 13.2 45.7 ± 13.1 45.3 ± 13.1 male, n (%) 652 (65.5) 472 (64.8) 491 (67.2) bmi, kg/m2, mean ± sd 30.4 ± 7.0 30.6 ± 7.1 30.2 ± 6.7 pso disease duration, years, mean ± sd 18.2 ± 12.5 18.2 ± 12.4 18.4 ± 12.6 pasi, mean ± sd 20.2 ± 7.8 20.2 ± 7.7 20.1 ± 7.8 prior treatments biologic therapy, n (%) 299 (30.1) 220 (30.2) 221 (30.2) anti-tnf 123 (12.4) 88 (12.1) 94 (12.9) anti-il-17 149 (15.0) 106 (14.6) 109 (14.9) anti-il-12/il-23 49 (4.9) 43 (5.9) 30 (4.1) systemic therapy for pso, n (%) 714 (71.8) 532 (73.1) 529 (72.4) table 2. overview of teaes in czp-treated patients to week 144 apatients who received both czp 200 mg q2w and czp 400 mg q2w are only included once in the population count for the ‘all czp’ group; bczp 200 mg q2w patients received a loading dose of czp 400 mg at weeks 0, 2, and 4 or weeks 16, 18, and 20; cone case each of acute myocardial infarction, cardiac arrest (due to liver failure and vasodilatory shock in association with hemorrhagic pancreatic necrosis), pneumonia legionella, cirrhosis alcoholic, chronic obstructive pulmonary disease, craniocerebral injury, and multiple injuries, the first two of which were considered related to the study drug by the investigator. ci: confidence interval; czp: certolizumab pegol; ir: incidence rate; py: patient-years; q2w: every two weeks; teae: treatment-emergent adverse event. all czpa (n=995) czp 400 mg q2w (n=728) czp 200 mg q2wb (n=731) total exposure, py 2,231 1,020 1,211 n (%) ir (95% ci) n (%) ir (95% ci) n (%) ir (95% ci) total teaes 847 (85.1) 144.9 (135.3, 155.0) 563 (77.3) 158.3 (145.5, 171.9) 557 (76.2) 134.1 (123.2, 145.7) total serious teaes 154 (15.5) 7.5 (6.4, 8.8) 82 (11.3) 8.7 (6.9, 10.8) 76 (10.4) 6.7 (5.2, 8.3) teaes leading to discontinuation 88 (8.8) 4.0 (3.2, 4.9) 48 (6.6) 4.7 (3.5, 6.3) 41 (5.6) 3.4 (2.5, 4.6) severe teaes 132 (13.3) 6.3 (5.3, 7.5) 70 (9.6) 7.2 (5.6, 9.1) 66 (9.0) 5.7 (4.4, 7.2) teaes leading to death 7 (0.7)c 0.3 (0.1, 0.6) 3 (0.4) 0.3 (0.1, 0.9) 4 (0.5) 0.3 (0.1, 0.8) a) cimpasi-1 and cimpasi-2 b) cimpact table 3. cumulative teaes over time at weeks 16, 48, 96, and 144 apatients who received both czp 200 mg q2w and czp 400 mg q2w are only included once in the population count for the ‘all czp’ group; bczp 200 mg q2w patients received a loading dose of czp 400 mg at weeks 0, 2, and 4 or weeks 16, 18, and 20. ci: confidence interval; czp: certolizumab pegol; ir: incidence rate; py: patient-years; q2w: every two weeks; teae: treatment-emergent adverse event. all czpa czp 400 mg q2w czp 200 mg q2wb placebo week 16 exposure, py n/n (%) ir (95% ci) 211 414/692 (59.8) 319.1 (289.1, 351.4) 105 217/342 (63.5) 348.3 (303.5, 397.9) 107 197/350 (56.3) 292.1 (252.7, 335.9) 47 97/157 (61.8) 342.6 (277.8, 417.9) week 48 exposure, py n/n (%) ir (95% ci) 729 709/962 (73.7) 219.6 (203.7, 236.4) 418 444/627 (70.8) 228.6 (207.8, 250.9) 311 321/460 (69.8) 221.2 (197.6, 246.7) – week 96 exposure, py n/n (%) ir (95% ci) 1,471 820/995 (82.4) 172.7 (161.1, 184.9) 700 528/711 (74.3) 186.4 (170.9, 203.0) 772 514/726 (70.8) 161.4 (147.8, 176.0) – week 144 exposure, py n/n (%) ir (95% ci) 2,231 847/995 (85.1) 144.9 (135.3, 155.0) 1,020 563/728 (77.3) 158.3 (145.5, 171.9) 1,211 557/731 (76.2) 134.1 (123.2, 145.7) – table 4. selected teaes and serious teaes of interest apatients who received both czp 200 mg q2w and czp 400 mg q2w are only included once in the population count for the ‘all czp’ group; bczp 200 mg q2w patients received a loading dose of czp 400 mg at weeks 0, 2, and 4 or weeks 16, 18, and 20; cinclusive of fatal and non-fatal myocardial infarction, serious cerebrovascular events and congestive heart failure (regardless of seriousness); dpatient with negative quantiferon tb gold test and normal chest x-ray before study entry who was randomized to etn, entered czp 400 mg q2w escape arm at week 16, and was diagnosed 60 days after czp initiation and discontinued the study; eone case of primary progressive multiple sclerosis (medical history indicated that symptoms pre-dated study entry); fone case of multiple sclerosis; gincludes one each of heart failure, congestive heart failure, acute coronary syndrome and extradural hematoma; hincludes one each of acute myocardial infarction, angina pectoris and cerebrovascular accident, and two transient ischemic attacks; iincludes one each of adenocarcinoma of colon, anaplastic oligodendroglioma, prostate cancer and clear cell renal cell carcinoma; jincludes one each of breast cancer, glioblastoma, hodgkin’s disease, laryngeal cancer, non-small cell lung cancer, oropharyngeal squamous cell carcinoma and prostate cancer; kincludes three basal cell carcinomas and one keratoacanthoma; lone basal cell carcinoma. ci: confidence interval; czp: certolizumab pegol; etn: etanercept; ir: incidence rate; nmsc: non-melanoma skin cancer; py: patient-years; q2w: every two weeks; tb: tuberculosis; teae: treatment-emergent adverse event. all czpa (n=995) czp 400 mg q2w (n=728) czp 200 mg q2wb (n=731) total exposure, py 2,231 1,020 1,211 n (%) ir (95% ci) n (%) ir (95% ci) n (%) ir (95% ci) serious infections 32 (3.2) 1.5 (1.0, 2.1) 16 (2.2) 1.6 (0.9, 2.6) 16 (2.2) 1.3 (0.8, 2.2) active tuberculosis 1 (0.1) 0.0 (0.0, 0.3) 1 (0.1)d 0.1 (0.0, 0.6) 0 (0.0) 0 (0.0, 0.0) demyelinating-like disorders 2 (0.2) 0.1 (0.0, 0.3) 1 (0.1)e 0.1 (0.0, 0.6) 1 (0.1)f 0.1 (0.0, 0.5) major adverse cardiac events (mace)c 9 (0.9) 0.4 (0.2, 0.8) 4 (0.5)g 0.4 (0.1, 1.0) 5 (0.7)h 0.4 (0.1, 1.0) congestive heart failure 1 (0.1) 0.0 (0.0, 0.3) 1 (0.1) 0.1 (0.0, 0.6) 0 (0.0) 0 (0.0, 0.0) all malignancies 14 (1.4) 0.6 (0.3, 1.1) 8 (1.1) 0.8 (0.3, 1.6) 8 (1.1) 0.7 (0.3, 1.3) malignancies excluding nmsc 10 (1.0) 0.5 (0.2, 0.8) 4 (0.5)i 0.4 (0.1, 1.0) 7 (1.0)j 0.6 (0.2, 1.2) nmsc 5 (0.5) 0.2 (0.1, 0.5) 4 (0.5)k 0.4 (0.1, 1.0) 1 (0.1)l 0.1 (0.0, 0.5) 0 16 484032week initial treatment period (double-blinded) <pasi 50 – withdrawn lda czp 200 mg q2w czp 400 mg q2w 14496 open-label treatment placebo q2w <pasi 50 – withdrawn <pasi 50 entered escape arm (czp 400 mg q2w) lda <pasi 50 – withdrawn ≥pasi 50, <pasi 75 czp 200 mg q2w czp 400 mg q2w ≥pasi 50 1: 2 :2 ra n d o m iz a ti o n maintenance period (double-blinded) ≥pasi 50 ≥pasi 50 open-label dose switching lda re-randomization initial treatment period (double-blinded) maintenance period (double-blinded) <pasi 75 <pasi 50 – open-label treatment <pasi 75 <pasi 75 <pasi 75 placebo q2w czp 400 mg q4wetn 50 mg bw washout lda czp 200 mg q2w czp 400 mg q2w czp 400 mg q2w czp 200 mg q2w placebo q2w <pasi 75 entered escape arm (czp 400 mg q2w) 1: 3 :3 :3 ra n d o m iz a ti o n 12 lda czp 400 mg q2w czp 200 mg q2w ≥pasi 50 <pasi 50 open-label treatment 96 1440 16 484032week open-label dose switching presented at winter clinical derm 2023, january 13–18, 2023 (encore of previous presentation at the american association for cancer research [aacr] 2022 annual meeting, april 8–13, lewis kd et al.). reused with permission. primary analysis of phase 2 results for cemiplimab in patients with metastatic basal cell carcinoma who progressed on or were intolerant to hedgehog inhibitors karl d lewis,1 ketty peris,2,3 aleksandar sekulic,4 alexander j stratigos,5 lara dunn,6 zeynep eroglu,7 anne lynn s chang,8 michael r migden,9 suk-young yoo,10 kosalai mohan,10 ebony coates,10 emmanuel okoye,10 jean-françois baurain,11 oliver bechter,12 axel hauschild,13 marcus o butler,14 leonel hernandez-aya,15† lisa licitra,16,17 rogerio i neves,18‡ emily s ruiz,19 frank seebach,10 israel lowy,10 priscila goncalves,10 matthew g fury10 1department of medicine-medical oncology, university of colorado school of medicine, aurora, co, usa; 2department of medicine and translational surgery, dermatology, università cattolica del sacro cuore, rome, italy; 3department of medical and surgical sciences, dermatology, fondazione policlinico universitario a gemelli-irccs, rome, italy; 4department of dermatology, mayo clinic, scottsdale, az, usa; 5first department of dermatology-venereology, national and kapodistrian university of athens, school of medicine, andreas sygros hospital, athens, greece; 6department of medicine, head and neck medical oncology, memorial sloan kettering cancer center, new york, ny, usa; 7department of cutaneous oncology, moffitt cancer center, tampa, fl, usa; 8dermatology department, stanford university school of medicine, redwood city, ca, usa; 9departments of dermatology and head and neck surgery, university of texas md anderson cancer center, houston, tx, usa; 10regeneron pharmaceuticals, inc., tarrytown, ny, usa; 11department of medical oncology, cliniques universitaires saint-luc and université catholique de louvain, brussels, belgium; 12department of general medical oncology, university hospitals, leuven, belgium; 13department of dermatology, university hospital schleswig-holstein (uksh), kiel, germany; 14division of medical oncology and hematology, princess margaret cancer centre, university of toronto, toronto, ontario, canada; 15division of medical oncology, department of medicine, washington university school of medicine, st louis, mo, usa; 16department of medical oncology head and neck cancer, istituto nazionale dei tumori, milan, italy; 17department of oncology and hemato-oncology, university of milan, milan, italy; 18division of plastic surgery, penn state milton s hershey medical center, hershey, pa, usa; 19department of dermatology, brigham and women’s hospital, harvard medical school, boston, ma, usa †current affiliation: department of internal medicine, sylvester comprehensive cancer center, university of miami, miami, fl, usa; ‡current affiliation: department of cutaneous oncology, moffitt cancer center and research institute, tampa, fl, usa background • in the us, basal cell carcinoma (bcc) is the most common non-melanoma skin cancer, with approximately 2.8 million cases per year, leading to >3000 deaths annually.1,2 • hedgehog inhibitors (hhis), such as vismodegib and sonidegib, are approved for the treatment of patients with locally advanced bcc (labcc) or metastatic bcc (mbcc) who are not candidates for surgery or radiation.3,4 • until recently, there were no approved agents for the treatment of bcc in patients who experienced progression of disease on hhi therapy, or who were intolerant to prior hhi therapy. • cemiplimab, an immunoglobulin g4 monoclonal antibody derived using velocimmune® technology, is a fully human, hinge-stabilized, high-affinity, high-potency blocker of programmed cell death-1 (pd-1).5 • in a pivotal phase 2 study of patients with advanced bcc who discontinued hhi therapy due to progressive disease, intolerance, or no better than stable disease after 9 months (nct03132636), cemiplimab became the first systemic therapy to show clinical benefit in patients with labcc after hhi therapy, with estimated duration of response (dor) exceeding 1 year in 85% of responders.6 • cemiplimab is approved in the us (generic name: cemiplimab-rwlc) for treatment of mbcc or labcc in patients previously treated with an hhi or for whom hhi therapy is not appropriate. cemiplimab-rwlc is approved in the us in certain patients with advanced cutaneous squamous cell carcinoma (cscc).7 • in europe, canada, and brazil, cemiplimab is also approved in certain patients with advanced bcc and cscc.8–11 objective • here, we present primary data analysis of patients in the mbcc cohort from the pivotal phase 2 study of cemiplimab in advanced bcc. key takeaways • cemiplimab provided clinically meaningful antitumor activity, including durable responses, in patients with mbcc who had progressed on or were intolerant to hhi therapy. • the safety profile was generally consistent with that previously described for cemiplimab and other pd-1 inhibitors. conclusion • these results complement those previously reported for the labcc cohort,6 and together indicate that cemiplimab is highly active in advanced bcc tumors. references 1. puig s et al. clin transl oncol. 2015;17:497–503. 2. mohan sv et al. curr dermatol rep. 2014;3:40–45. 3. sun pharma global fze. available from: https://www.accessdata.fda.gov/ drugsatfda_docs/label/2017/205266s004lbl.pdf. accessed june 10, 2021. 4. roche. available from: https://www.gene.com/download/pdf/erivedge_ prescribing.pdf. accessed june 10, 2021. 5. burova e et al. mol cancer ther. 2017;16:861–870. 6. stratigos aj et al. lancet oncol. 2021;22:848–857. 7. regeneron pharmaceuticals, inc. available from: https://www.accessdata.fda.gov/ drugsatfda_docs/label/2021/761097s007lbl.pdf. accessed january 28, 2022. 8. european medicines agency. available from: https://www.ema.europa.eu/en/ medicines/human/epar/libtayo. accessed december 3, 2021. 9. sanofi-aventis canada, inc. available from: https://pdf.hres.ca/dpd_ pm/00063482.pdf. accessed february 23, 2022. 10. health canada. available from: https://www.canada.ca/en/health-canada/ services/drugs-health-products/drug-products/notice-compliance/conditions/ libtayo-notice-compliance-conditions-218718.html. accessed january 28, 2022. 11. brazilian health authority anvisa. available from: https://www.gov.br/anvisa/ pt-br/assuntos/medicamentos/novos-medicamentos-e-indicacoes/libtayocemiplimabe-nova-indicacao. accessed january 28, 2022. 12. eisenhauer ea et al. eur j cancer. 2009;45:228–247. acknowledgments the authors thank the patients, their families, investigators, and all investigational site members involved in this study. this study was funded by regeneron pharmaceuticals, inc., and sanofi. medical writing support was provided by daniel m himmel, phd, of prime, knutsford, uk, funded by regeneron pharmaceuticals, inc., and sanofi. disclosure karl d lewis reports grants and personal fees from regeneron pharmaceuticals, inc., during the conduct of the study; consulting or advisory roles from array biopharma, merck, roche, regeneron pharmaceuticals, inc., sanofi, and iovance biotherapeutics; travel, accommodations, and expenses from merck, roche/genentech, regeneron pharmaceuticals, inc., neon therapeutics, and alkermes; honoraria from array biopharma and iovance biotherapeutics; institutional research funding from roche/genentech, merck, array biopharma, incyte, nektar, iovance biotherapeutics, bristol-myers squibb, kartos therapeutics, oncosec, regeneron pharmaceuticals, inc., alkermes, neon therapeutics, ultimovacs, senhwa biosciences, replimune, and amgen; and uncompensated relationships at roche/genentech and regeneron pharmaceuticals, inc. methods • after a screening period of up to 28 days, patients received cemiplimab 350 mg every 3 weeks for 93 weeks, followed by four 12-week cycles or until disease progression, unacceptable toxicity, or withdrawal of consent (figure 1). • inclusion and exclusion criteria are provided in table 1. results patient demographics and baseline characteristics • as of data cutoff (may 20, 2021), 54 patients were enrolled; median age was 63.5 years (range, 38−90) and 70.4% of patients were male (table 2). • the most common primary tumor sites were the trunk (46.3%) and the head and neck (40.7%) (table 2). • the most common reasons for discontinuation of hhi therapy were progression of disease on hhi (75.9%) or intolerance to hhi (33.3%) (table 2). tumor response • median duration of follow-up was 8.4 months (range, 1.5–36.2). • objective response rate (orr) per independent central review (icr) was 24.1% (95% confidence interval [ci], 13.5–37.6); with one complete response and 12 partial responses (figure 2, table 3). orr per investigator assessment (inv) was 25.9% (95% ci, 15.0–39.7), with two complete responses and 12 partial responses. • among responders, median time to response was 4.0 months (range, 2.0−10.5) per icr. • estimated median duration of response (dor) per icr was 16.7 months (95% ci, 9.8–not evaluable [ne]). • median overall survival (os) was not reached (95% ci, 25.7–ne) (figure 3). the 12-month kaplan-meier (km) estimation of os was 84.4% (95% ci, 71.3–91.9). • median km estimation of progression-free survival (pfs) was 8.3 months (95% ci, 4.2–15.9) per icr (figure 4). safety • the most common treatment-emergent adverse events (teaes) of any grade were fatigue (42.6%; n=23), diarrhea (37.0%; n=20), constipation (22.2%; n=12), and hypertension (20.4%; n=11) (table 4). • immune-related adverse events (iraes) of any grade occurred in 61.1% (n=33) of patients. • grade ≥3 iraes were seen in 9.3% (n=5) of patients; the only grade ≥3 iraes occurring in more than one patient was colitis. • two patients (3.7%) had a serious teae resulting in death: staphylococcal pneumonia (n=1) and hemoptysis (n=1). • there were no treatment-related deaths. †or by composite response criteria for patient with both visceral and skin lesions. bcc, basal cell carcinoma; dor, duration of response; icr, independent central review; inv, investigator assessment; iv, intravenous; labcc, locally advanced basal cell carcinoma; orr, objective response rate; os, overall survival; pfs, progression-free survival; q3w, every 3 weeks; q9w, every 9 weeks; q12w, every 12 weeks; recist 1.1, response evaluation criteria in solid tumors version 1.1; who, world health organization. figure 1. study design group 1: adult patients with metastatic (nodal and distant) bcc group 2: adult patients with labcc cemiplimab 350 mg iv q3w for up to 93 weeks (or until disease progression, unacceptable toxicity, or withdrawal of consent) tumor assessments 1–5 q9w, 6–9 q12w tumor response assessment by icr (recist 1.1 for visceral lesions or modified who criteria for skin lesions)† primary endpoint: orr per icr key secondary endpoints: orr per inv, dor, pfs, os, complete response per icr, and safety and tolerability. table 1. inclusion and exclusion criteria inclusion criteria exclusion criteria • age ≥18 years • ecog performance status of 0 or 1 • histologically confirmed diagnosis of invasive bcc • progression of disease on or intolerance to previous hhi therapy or having no better than stable disease after 9 months on hhi therapy • at least one measurable baseline lesion12 • ongoing or recent (within 5 years) evidence of substantial autoimmune disease requiring systemic immunosuppression • previous treatment with an anti–pd-1 or an anti–pd-l1 drug • untreated brain metastases that may be considered active • concurrent malignancy other than bcc or history of malignancy other than bcc within 3 years of date of first planned dose of cemiplimab, except for tumors with negligible risk of metastasis or death bcc, basal cell carcinoma; ecog, eastern cooperative oncology group; hhi, hedgehog inhibitor; pd-1, programmed cell death-1; pd-l1, programmed cell death-ligand 1. table 2. patient demographic and baseline characteristics characteristic mbcc (n=54) age, median (range), years 63.5 (38–90) ≥65 years, n (%) 27 (50.0) male, n (%) 38 (70.4) ecog performance status, n (%) 0 36 (66.7) 1 18 (33.3) number of patients with prior hhi therapy, n (%) vismodegib 52 (96.3) sonidegib 9 (16.7) vismodegib + sonidegib 7 (13.0) reason for discontinuation of prior hhi, n (%)† progression of disease on hhi 41 (75.9) intolerant to prior hhi therapy 18 (33.3) intolerant to vismodegib 19 (35.2) intolerant to sonidegib 5 (9.3) no better than stable disease after 9 months on hhi therapy 7 (13.0) primary tumor site, n (%) head and neck 22 (40.7) trunk 25 (46.3) extremity 6 (11.1) anogenital 1 (1.9) metastatic status, n (%) distant only 19 (35.2) distant and nodal 29 (53.7) nodal only 5 (9.3) †sum is >54 because some patients had more than one reason for discontinuation. ecog, eastern cooperative oncology group; hhi, hedgehog inhibitor; mbcc, metastatic basal cell carcinoma. figure 2. time to and duration of response in responding patients per icr each horizontal bar represents one patient. a gray arrow indicates a patient still on study. patients with confirmed complete response after a minimum of 48 weeks of treatment could elect to discontinue treatment and continue with all relevant study assessments. icr, independent central review; mbcc, metastatic basal cell carcinoma. p a ti e n ts w it h r e s p o n s e ( n = 1 3 ) month patients with mbcc 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 complete response partial response stable disease progressive disease unable to evaluate ongoing treatment on study figure 3. km curve for os km, kaplan-meier; mbcc, metastatic basal cell carcinoma; os, overall survival. 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 p ro b a b ili ty o f s u rv iv a l month 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 group 1: mbcc number of patients at risk 54 53 52 50 44 44 41 35 31 30 26 22 19 17 12 11 8 7 6 2 1 0 0 figure 4. km curve for pfs per icr patients with confirmed complete response after a minimum of 48 weeks of treatment could elect to discontinue treatment and continue with all relevant study assessments. icr, independent central review; km, kaplan-meier; mbcc, metastatic basal cell carcinoma; pfs, progression-free survival. 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0p ro b a b ili ty o f p ro g re s s io n -f re e s u rv iv a l month 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 group 1: mbcc number of patients at risk 54 50 31 26 24 22 19 10 9 9 4 3 3 2 2 2 1 1 1 0 0 0 0 table 3. tumor response per icr response mbcc (n=54) best overall response orr, % (95% cl) 24.1 (13.5–37.6)# complete response, n (%) 1 (1.9) partial response, n (%) 12 (22.2) stable disease, n (%) 16 (29.6) non-complete response/non-progressive disease, n (%) 5 (9.3) progressive disease, n (%) 16 (29.6) ne,† n (%) 4 (7.4) disease control rate, % (95% ci)‡ 63.0 (48.7–75.7) durable disease control rate, % (95% ci)§ 42.6 (29.2–56.8) time to response, median (range), months¶ 4.0 (2.0–10.5) km estimation of dor, median (95% ci), months 16.7 (9.8−ne) 6 months 100 (ne–ne) 12 months 53.5 (21.2−77.7) km estimation of pfs, median (95% ci), months 8.3 (4.2–15.9) †ne response includes missing and unknown tumor response. ‡defined as the proportion of patients with complete response, partial response, stable disease or non-complete response/non-progressive disease. §defined as the proportion of patients with complete response, partial response, stable disease, or non-complete response/non-progressive disease for ≥182 days without progressive disease. ¶data shown are for patients with response. #orr per investigator assessment was 25.9% (15.0–39.7). ci, confidence interval; dor, duration of response; icr, independent central review; km, kaplan-meier; mbcc, metastatic basal cell carcinoma; ne, not evaluable; orr, objective response rate; pfs, progression-free survival. table 4. teaes regardless of attribution† mbcc (n=54) n (%) any grade grade ≥3 any teae 51 (94.4) 23 (42.6) serious teaes 16 (29.6) 15 (27.8) teaes leading to treatment discontinuation 4 (7.4) 3 (5.6) teaes associated with an outcome of death‡ 2 (3.7) 2 (3.7) any teae occurring in ≥10% patients§ fatigue 23 (42.6) 0 diarrhea 20 (37.0) 0 constipation 12 (22.2) 0 hypertension 11 (20.4) 6 (11.1) arthralgia 9 (16.7) 0 pruritus 8 (14.8) 0 pyrexia 8 (14.8) 1 (1.9) weight increased 8 (14.8) 0 vomiting 7 (13.0) 0 edema peripheral 6 (11.1) 0 pain in extremity 6 (11.1) 1 (1.9) decreased appetite 6 (11.1) 1 (1.9) headache 6 (11.1) 1 (1.9) nausea 6 (11.1) 0 anemia 6 (11.1) 0 hyperglycemia 6 (11.1) 1 (1.9) †adverse events were coded according to the preferred terms of the medical dictionary for regulatory activities, version 22.1. the severity of adverse events was graded according to national cancer institute common terminology criteria for adverse events, version 4.03. ‡adverse events leading to death were staphylococcal pneumonia and hemoptysis, deemed unrelated to treatment. §events are listed in descending order of frequency in any grade. mbcc, metastatic basal cell carcinoma; teae, treatment-emergent adverse event. scan the qr code for co-author disclosures indirect comparison of the short-, mid-, and long-term efficacy of treatments for moderate to severe plaque psoriasis: a systematic review and network meta-analysis april armstrong,1 richard b. warren,2 yichen zhong,3 joe zhuo,3 allie cichewicz,4 ananth kadambi,4 daniela r. junqueira,4 tracy westley,4 renata kisa,3 carolin daamen,3 matthias augustin5 1university of southern california, los angeles, ca; 2the university of manchester, manchester, uk; 3bristol myers squibb, princeton, nj; 4evidera, bethesda, md; 5university medical center, hamburg, germany presented at the fall clinical dermatology conference; october 20–23, 2022; las vegas, nv this poster may not be reproduced without written permission from the authors.email for april armstrong, md, mph: aprilarmstrong@post.harvard.edu scientifi c content on demand to request a copy of this poster: scan qr code via a barcode reader application qr codes are valid for 30 days after congress presentation date synopsis • patients with moderate to severe plaque psoriasis have several systemic treatment choices available, including oral nonbiologic and biologic options • deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 (tyk2) inhibitor, demonstrated superior effi cacy versus apremilast and placebo in two phase 3 randomized controlled trials (rcts) and is approved by the us food and drug administration for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy • this systematic literature review (slr) and network meta-analysis (nma) indirectly compared the efficacy of deucravacitinib with that of other approved, relevant systemic biologic and nonbiologic treatments over short-, medium-, and long-term follow-up; multinomial random effects models estimated improvement in responses on the psoriasis area and severity index (pasi) at weeks 10−16, 24−28, and 44−60 • pasi 75 (75% improvement in pasi) response rate with deucravacitinib was comparable to that of first-generation biologics at week 16, and higher at week 24; at week 52, it was comparable to that of the most effective fi rstgeneration biologics objective • the objective of this analysis was to examine the clinical effi cacy associated with deucravacitinib and other selected active biologic and nonbiologic treatments in patients with moderate to severe psoriasis methods • electronic databases were searched through october 2021 for rcts of systemic treatments in adults with moderate to severe psoriasis who reported improvement in response on pasi • phase 3 trial data were included when: — nonresponder imputation was applied1,2 — studies were conducted in multiple or single countries with diverse ethnic representation • nma was performed using multinomial random effects models adjusting for baseline risk (ie, placebo response) to estimate pasi responses over short-, mid-, and long-term follow-up periods (weeks 10−16, 24−28, and 44−60, respectively) and reported following the prisma reporting guidelines for meta-analysis3 results • the slr identifi ed 47 phase 3 rcts that applied nonresponder imputation and were included in the nma (figure 1 and figure 2a); the mid-term analysis included 28 studies (figure 2b); the long-term analysis included 21 studies (figure 2c) figure 1. prisma flow diagram full-text articles excluded (n = 446) • duplicates (n = 11) • publication type not of interest (n = 17) • study design not of interest (n = 25) • population not of interest (n = 60) • intervention/comparator not of interest (n = 105) • outcomes not of interest (n = 189) • relevant slrs/nmas published 2019-2020 (n = 39) records excluded by title and abstract screening (n = 3632) full-text articles assessed for eligibility (n = 818) 251 rct publications and 132 pooleda analyses included in slr duplicates removed (n = 3037) rcts included in global pasi nma (n = 96 unique rcts)b records screened (n = 4450) rcts included in phase 3 global nri pasi nma (n = 47 unique rcts)b id e n ti fi ca ti o n sc re e n in g e li gi b il it y in cl u d e d records identified through database searching (n = 7487) records identified through other sources (conference proceedings: n = 11) apooled analyses of rcts were not included in the slr unless unique data were available that were not published elsewhere. brcts eligible for global pasi nma and phase 3 global nri pasi nma, including poetyk ps0-1 and poetyk pso-2. nma, network meta-analysis; nri, nonresponder imputation; pasi, psoriasis area and severity index; rct, randomized controlled trial; slr, systematic literature review. figure 2. network plots of trials included in the shortterm (10–16 weeks; a), mid-term (24–28 weeks; b), and long-term (44–60 weeks; c) analyses v etanercept study group liberate etanercept study group etanercept study group fixture m10-114 m10-315 opt compare study resurface 2 uncover 2, 3 liberate esteem 1, 2 liberate poetyk 1, 2poetyk 1, 2 fixture poetyk 1, 2 uncover 2, 3 uncover 1, 2, 3 erasure feature fixture juncture allure erasure feature fixture juncture amagine 2, 3 be vivid ultimma-1, -2 amagine 1, 2, 3 amagine 2, 3 clear immerge be vivid be radiant be ready be vivid orion voyage 1, 2 voyage 1, 2 be sure immvent voyage 1, 2 reveal champion express express ii spirit restore 1 resurface 1, 2 resurface 1, 2 phoenix 1, 2 resurface 1, 2 resurface 2 accept ust 90 mg til 200 mg til 100 mg ifx 5 mg/kg mtx 7.5 to 25 mg adm 40 mggus 100 mg bim 320 mg ust 45 or 90 mg sec 300 mg sec 150 mg apr 30 mg etc 25 mg biw etc 50 mg biw deuc 6 mg ixe 80 mg q2w bro 210 mg ris 150 mg pbo resurface 2 fixture reich, 2020 champion champion metop eclipse blauvelt, 2021 immhance ultimma-1, -2 ultimma-1, -2 ixora-5 erasure feature fixture juncture a. erasure feature fixture juncture erasure feature fixture juncture erasure feature fixture juncture amagine 2, 3 be vivid ultimma-1, -2 ultimma-1, -2 ultimma-1, -2 poetyk 1 uncover 3 amagine 2, 3 amagine 2, 3 immerge be radiant voyage 1 voyage 1 voyage 1 express express ii fixture fixturefixture metop eclipseixora-5 ifx 5 mg/kg mtx 7.5 to 25 mg adm 40 mggus 100 mg bim 320 mg ust 45 or 90 mg sec 300 mg sec 150 mg apr 30 mg etc 50 mg biw deuc 6 mg ixe 80 mg q2w bro 210 mg ris 150 mg pbo liberate clear c. etanercept study group etanercept study group esteem 1, 2 poetyk 1, 2poetyk 1, 2 fixture poetyk 1, 2 uncover 3 erasure feature fixture erasure feature fixture allure erasure feature fixture amagine 2, 3 be vivid amagine 1, 2, 3 amagine 2, 3 clear immhance immerge be radiant orion voyage 1, 2 voyage 1, 2 voyage 1, 2 be sure express express ii resurface 1, 2 resurface 1, 2 phoenix 1, 2 resurface 2 ust 90 mg til 200 mg til 100 mg ifx 5 mg/kg mtx 7.5 to 25 mg adm 40 mggus 100 mg bim 320 mg ust 45 or 90 mg sec 300 mg sec 150 mg apr 30 mg etc 25 mg biw etc 50 mg biw deuc 6 mg ixe 80 mg q2w bro 210 mg ris 150 mg pbo resurface 2 fixture metop eclipse ixora-5 resurface 1, 2 b. etanercept study group fixture resurface 2 act, acitretin; adm, adalimumab; apr, apremilast; bim, bimekizumab; biw, twice weekly; bro, brodalumab; deuc, deucravacitinib; etc, etanercept; gus, guselkumab; ifx, infl iximab; ixe, ixekizumab; mtx, methotrexate; pbo, placebo; ris, risankizumab; q2w, once every 2 weeks; sec, secukinumab; til, tildrakizumab; ust, ustekinumab. • pasi 75 response rate with deucravacitinib at week 16 (54.1%; credible interval [crl], 46.5%, 61.6%) was within range of the first-generation biologics (range, 39.7 [crl, 31.6%, 48.3%] for etanercept 25 mg to 79.0% [crl, 74.0%, 83.5%] for infl iximab; figure 3a) • pasi 75 response with deucravacitinib increased at week 24 to 63.3% (crl, 58.0%, 68.4%; figure 3b) • at week 52, the pasi 75 response rate for deucravacitinib (65.9%; crl, 58.0%, 73.4%) was comparable to that of the most effective first-generation biologics — adalimumab (62.8%; crl, 55.3%, 69.6%) and ustekinumab (68.0%; crl, 64.6%, 71.5%; figure 3c) • newer il-17 and il-23 inhibitors showed the highest pasi 75 response rates of the included treatments, across all time points figure 3. short-term estimated pasi 75 response,a posterior median and 95% cri. weeks 10–16 (a), midterm estimated pasi 75 response for weeks 24–28 (b), and long-term estimated pasi 75 response for weeks 44–60 (c) 56.7 ifx 5 mg/kg adm 40 mg 62.8 48.4 apr 30 mg 45.0 mtx ust 90 mg 70.9 ust 45 or 90 mg 71.1 5.8 33.5 40.1 54.1 39.7 49.8 71.7 79.0 84.8 85.7 89.0 93.0 63.0 64.2 87.8 89.6 0 10 20 30 40 50 60 70 80 90 100 pbo apr 30 mg mtx deuc 6 mg etc 25 mg biw/50 mg qw etc 50 mg biw adm 40 mg ifx 5 mg/kg sec 150 mg sec 300 mg bro 210 mg ixe 80 mg q2w bim 320b mg til 100 mg til 200 mg gus 100 mg ris 150 mg n m a e st im at e d p a si 7 5 re sp on se r at e , % nonbiologic oral anti-tnf anti–il-12/23 anti–il-17 anti–il-23 first-generation biologics second-generation biologics a. 71.3 6.4 54.0 77.0 81.0 83.9 86.4 87.8 91.6 0 10 20 30 40 50 60 70 80 90 100 pbo deuc 6 mg etc 50 mg biw ust 45 or 90 mg sec 150 mg sec 300 mg bro 210 mg ixe 80 mg q2w>q4w bim 320b mg q4w>q8w gus 100 mg ris 150 mg n m a e st im at e d p a si 7 5 re sp on se r at e , % nonbiologic oral anti-tnf anti–il–12/23 anti–il-17 anti–il-23 c. 62.1 68.0 65.9 6.4 34.8 50.1 63.3 43.7 54.4 84.7 86.2 89.6 92.1 89.5 93.8 0 10 20 30 40 50 60 70 80 90 100 pbo apr 30 mg mtx deuc 6 mg etc 25 mg biw/50 mg qw etc 50 mg biw adm 40 mg ifx 5 mg/kg ust 45 or 90 mg ust 90 mg sec 150 mg sec 300 mg bro 210 mg ixe 80 mg q2w>q4w bim 320b mg q4w>q8w til 100 mg til 200 mg gus 100 mg ris 150 mg n m a e st im at e d p a si 7 5 re sp on se r at e , % nonbiologic oral anti–tnf anti–il-12/23 anti–il-17 anti–il-23 b. 74.675.074.271.0 72.3 72.2 73.4 first-generation biologics second-generation biologics first-generation biologics second-generation biologics aadjusted for placebo response rates. bbim is not approved for use in the united states. note: posterior median value given for each therapy; error bars represent 95% cri. adm, adalimumab; apr, apremilast; bim, bimekizumab; biw, twice weekly; bro, brodalumab; cri, credible interval; deuc, deucravacitinib; etc, etanercept; gus, guselkumab; ifx, infl iximab; il, interleukin; ixe, ixekizumab; mtx, methotrexate; nma, network meta-analysis; pasi, psoriasis area and severity index; pbo, placebo; q2w, once every 2 weeks; q4w, once every 4 weeks; q8w, once every 8 weeks; ris, risankizumab; sec, secukinumab; til, tildrakizumab; tnf, tumor necrosis factor; ust, ustekinumab. conclusions • among oral nonbiologic treatments, deucravacitinib provided the best efficacy across time points compared with methotrexate and apremilast • the pasi 75 response rates for deucravacitinib were within the range of those for first-generation biologics at weeks 10–16 and 24–28 • at 1 year, the pasi 75 response rate for deucravacitinib was similar to that of adalimumab and ustekinumab • the psoriasis treatment paradigm is changing with the approval of deucravacitinib, a convenient oral therapy with a long-term effi cacy level similar to that of some biologic therapies references 1. guideline on missing data in confirmatory clinical trials. european medicines agency; 2010. https://www.ema.europa.eu/en/documents/ scientifi c-guideline/guideline-missing-data-confi rmatory-clinical-trials_ en.pdf 2. guidance for sponsors, clinical investigators, and irbs. us food and drug administration; 2008. http://www.fda.gov/downloads/ regulatoryinformation/guidances/ucm126489.pdf 3. page mj, et al. plos med. 2021;18:e1003583. acknowledgments • this study was sponsored by bristol myers squibb • medical writing and editorial assistance was provided by cheryl jones of peloton advantage, llc, an open health company, and funded by bristol myers squibb disclosures • aa: grants and personal fees: abbvie, bristol myers squibb, eli lilly, janssen, leo pharma, and novartis; personal fees: boehringer ingelheim/parexel, celgene, dermavant, genentech, glaxosmithkline, menlo therapeutics, merck, modernizing medicine, ortho dermatologics, pfizer, regeneron, sanofi genzyme, science 37, sun pharma, and valeant; grants: dermira, kyowa hakko kirin, and ucb, outside the submitted work • rbw: research grants: abbvie, almirall, amgen, celgene, eli lilly, janssen, leo pharma, novartis, pfizer, and ucb; consulting fees: abbvie, almirall, amgen, biogen, boehringer ingelheim, celgene, dice, eli lilly, janssen, leo pharma, novartis, pfizer, sanofi, ucb, and union • yz, jz, rk, and cd: employees of and may own stock options in bristol myers squibb • ac, ak, dj, and tw: employed by evidera, a company that provides consulting and other research services to bristol myers squibb • ma: advisory boards: abbvie, amgen, boehringer ingelheim, janssen biotech, and leo pharma; consulting fees: abbvie, amgen, eli lilly, janssen biotech, leo pharma, novartis, sun pharma, and ucb; honoraria: abbvie, amgen, boehringer ingelheim, eli lilly, janssen biotech, leo pharma, novartis, sun pharma, and ucb; investigator: abbvie, amgen, boehringer ingelheim, celgene, eli lilly, janssen biotech, leo pharma, merck, novartis, sun pharma, and ucb; research grants: abbvie, amgen, boehringer ingelheim, celgene, janssen biotech, leo pharma, merck, and sun pharma; speaker: abbvie, amgen, janssen biotech, leo pharma, sun pharma, and ucb indirect comparison of the short-, mid-, and long-term efficacy of treatments for moderate to severe plaque psoriasis: a systematic review and network meta-analysis april armstrong,1 richard b. warren,2 yichen zhong,3 joe zhuo,3 allie cichewicz,4 ananth kadambi,4 daniela r. junqueira,4 tracy westley,4 renata kisa,3 carolin daamen,3 matthias augustin5 1university of southern california, los angeles, ca; 2the university of manchester, manchester, uk; 3bristol myers squibb, princeton, nj; 4evidera, bethesda, md; 5university medical center, hamburg, germany presented at the fall clinical dermatology conference; october 20–23, 2022; las vegas, nv this poster may not be reproduced without written permission from the authors.email for april armstrong, md, mph: aprilarmstrong@post.harvard.edu scientifi c content on demand to request a copy of this poster: scan qr code via a barcode reader application qr codes are valid for 30 days after congress presentation date synopsis • patients with moderate to severe plaque psoriasis have several systemic treatment choices available, including oral nonbiologic and biologic options • deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 (tyk2) inhibitor, demonstrated superior effi cacy versus apremilast and placebo in two phase 3 randomized controlled trials (rcts) and is approved by the us food and drug administration for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy • this systematic literature review (slr) and network meta-analysis (nma) indirectly compared the efficacy of deucravacitinib with that of other approved, relevant systemic biologic and nonbiologic treatments over short-, medium-, and long-term follow-up; multinomial random effects models estimated improvement in responses on the psoriasis area and severity index (pasi) at weeks 10−16, 24−28, and 44−60 • pasi 75 (75% improvement in pasi) response rate with deucravacitinib was comparable to that of first-generation biologics at week 16, and higher at week 24; at week 52, it was comparable to that of the most effective fi rstgeneration biologics objective • the objective of this analysis was to examine the clinical effi cacy associated with deucravacitinib and other selected active biologic and nonbiologic treatments in patients with moderate to severe psoriasis methods • electronic databases were searched through october 2021 for rcts of systemic treatments in adults with moderate to severe psoriasis who reported improvement in response on pasi • phase 3 trial data were included when: — nonresponder imputation was applied1,2 — studies were conducted in multiple or single countries with diverse ethnic representation • nma was performed using multinomial random effects models adjusting for baseline risk (ie, placebo response) to estimate pasi responses over short-, mid-, and long-term follow-up periods (weeks 10−16, 24−28, and 44−60, respectively) and reported following the prisma reporting guidelines for meta-analysis3 results • the slr identifi ed 47 phase 3 rcts that applied nonresponder imputation and were included in the nma (figure 1 and figure 2a); the mid-term analysis included 28 studies (figure 2b); the long-term analysis included 21 studies (figure 2c) figure 1. prisma flow diagram full-text articles excluded (n = 446) • duplicates (n = 11) • publication type not of interest (n = 17) • study design not of interest (n = 25) • population not of interest (n = 60) • intervention/comparator not of interest (n = 105) • outcomes not of interest (n = 189) • relevant slrs/nmas published 2019-2020 (n = 39) records excluded by title and abstract screening (n = 3632) full-text articles assessed for eligibility (n = 818) 251 rct publications and 132 pooleda analyses included in slr duplicates removed (n = 3037) rcts included in global pasi nma (n = 96 unique rcts)b records screened (n = 4450) rcts included in phase 3 global nri pasi nma (n = 47 unique rcts)b id e n ti fi ca ti o n sc re e n in g e li gi b il it y in cl u d e d records identified through database searching (n = 7487) records identified through other sources (conference proceedings: n = 11) apooled analyses of rcts were not included in the slr unless unique data were available that were not published elsewhere. brcts eligible for global pasi nma and phase 3 global nri pasi nma, including poetyk ps0-1 and poetyk pso-2. nma, network meta-analysis; nri, nonresponder imputation; pasi, psoriasis area and severity index; rct, randomized controlled trial; slr, systematic literature review. figure 2. network plots of trials included in the shortterm (10–16 weeks; a), mid-term (24–28 weeks; b), and long-term (44–60 weeks; c) analyses v etanercept study group liberate etanercept study group etanercept study group fixture m10-114 m10-315 opt compare study resurface 2 uncover 2, 3 liberate esteem 1, 2 liberate poetyk 1, 2poetyk 1, 2 fixture poetyk 1, 2 uncover 2, 3 uncover 1, 2, 3 erasure feature fixture juncture allure erasure feature fixture juncture amagine 2, 3 be vivid ultimma-1, -2 amagine 1, 2, 3 amagine 2, 3 clear immerge be vivid be radiant be ready be vivid orion voyage 1, 2 voyage 1, 2 be sure immvent voyage 1, 2 reveal champion express express ii spirit restore 1 resurface 1, 2 resurface 1, 2 phoenix 1, 2 resurface 1, 2 resurface 2 accept ust 90 mg til 200 mg til 100 mg ifx 5 mg/kg mtx 7.5 to 25 mg adm 40 mggus 100 mg bim 320 mg ust 45 or 90 mg sec 300 mg sec 150 mg apr 30 mg etc 25 mg biw etc 50 mg biw deuc 6 mg ixe 80 mg q2w bro 210 mg ris 150 mg pbo resurface 2 fixture reich, 2020 champion champion metop eclipse blauvelt, 2021 immhance ultimma-1, -2 ultimma-1, -2 ixora-5 erasure feature fixture juncture a. erasure feature fixture juncture erasure feature fixture juncture erasure feature fixture juncture amagine 2, 3 be vivid ultimma-1, -2 ultimma-1, -2 ultimma-1, -2 poetyk 1 uncover 3 amagine 2, 3 amagine 2, 3 immerge be radiant voyage 1 voyage 1 voyage 1 express express ii fixture fixturefixture metop eclipseixora-5 ifx 5 mg/kg mtx 7.5 to 25 mg adm 40 mggus 100 mg bim 320 mg ust 45 or 90 mg sec 300 mg sec 150 mg apr 30 mg etc 50 mg biw deuc 6 mg ixe 80 mg q2w bro 210 mg ris 150 mg pbo liberate clear c. etanercept study group etanercept study group esteem 1, 2 poetyk 1, 2poetyk 1, 2 fixture poetyk 1, 2 uncover 3 erasure feature fixture erasure feature fixture allure erasure feature fixture amagine 2, 3 be vivid amagine 1, 2, 3 amagine 2, 3 clear immhance immerge be radiant orion voyage 1, 2 voyage 1, 2 voyage 1, 2 be sure express express ii resurface 1, 2 resurface 1, 2 phoenix 1, 2 resurface 2 ust 90 mg til 200 mg til 100 mg ifx 5 mg/kg mtx 7.5 to 25 mg adm 40 mggus 100 mg bim 320 mg ust 45 or 90 mg sec 300 mg sec 150 mg apr 30 mg etc 25 mg biw etc 50 mg biw deuc 6 mg ixe 80 mg q2w bro 210 mg ris 150 mg pbo resurface 2 fixture metop eclipse ixora-5 resurface 1, 2 b. etanercept study group fixture resurface 2 act, acitretin; adm, adalimumab; apr, apremilast; bim, bimekizumab; biw, twice weekly; bro, brodalumab; deuc, deucravacitinib; etc, etanercept; gus, guselkumab; ifx, infl iximab; ixe, ixekizumab; mtx, methotrexate; pbo, placebo; ris, risankizumab; q2w, once every 2 weeks; sec, secukinumab; til, tildrakizumab; ust, ustekinumab. • pasi 75 response rate with deucravacitinib at week 16 (54.1%; credible interval [crl], 46.5%, 61.6%) was within range of the first-generation biologics (range, 39.7 [crl, 31.6%, 48.3%] for etanercept 25 mg to 79.0% [crl, 74.0%, 83.5%] for infl iximab; figure 3a) • pasi 75 response with deucravacitinib increased at week 24 to 63.3% (crl, 58.0%, 68.4%; figure 3b) • at week 52, the pasi 75 response rate for deucravacitinib (65.9%; crl, 58.0%, 73.4%) was comparable to that of the most effective first-generation biologics — adalimumab (62.8%; crl, 55.3%, 69.6%) and ustekinumab (68.0%; crl, 64.6%, 71.5%; figure 3c) • newer il-17 and il-23 inhibitors showed the highest pasi 75 response rates of the included treatments, across all time points figure 3. short-term estimated pasi 75 response,a posterior median and 95% cri. weeks 10–16 (a), midterm estimated pasi 75 response for weeks 24–28 (b), and long-term estimated pasi 75 response for weeks 44–60 (c) 56.7 ifx 5 mg/kg adm 40 mg 62.8 48.4 apr 30 mg 45.0 mtx ust 90 mg 70.9 ust 45 or 90 mg 71.1 5.8 33.5 40.1 54.1 39.7 49.8 71.7 79.0 84.8 85.7 89.0 93.0 63.0 64.2 87.8 89.6 0 10 20 30 40 50 60 70 80 90 100 pbo apr 30 mg mtx deuc 6 mg etc 25 mg biw/50 mg qw etc 50 mg biw adm 40 mg ifx 5 mg/kg sec 150 mg sec 300 mg bro 210 mg ixe 80 mg q2w bim 320b mg til 100 mg til 200 mg gus 100 mg ris 150 mg n m a e st im at e d p a si 7 5 re sp on se r at e , % nonbiologic oral anti-tnf anti–il-12/23 anti–il-17 anti–il-23 first-generation biologics second-generation biologics a. 71.3 6.4 54.0 77.0 81.0 83.9 86.4 87.8 91.6 0 10 20 30 40 50 60 70 80 90 100 pbo deuc 6 mg etc 50 mg biw ust 45 or 90 mg sec 150 mg sec 300 mg bro 210 mg ixe 80 mg q2w>q4w bim 320b mg q4w>q8w gus 100 mg ris 150 mg n m a e st im at e d p a si 7 5 re sp on se r at e , % nonbiologic oral anti-tnf anti–il–12/23 anti–il-17 anti–il-23 c. 62.1 68.0 65.9 6.4 34.8 50.1 63.3 43.7 54.4 84.7 86.2 89.6 92.1 89.5 93.8 0 10 20 30 40 50 60 70 80 90 100 pbo apr 30 mg mtx deuc 6 mg etc 25 mg biw/50 mg qw etc 50 mg biw adm 40 mg ifx 5 mg/kg ust 45 or 90 mg ust 90 mg sec 150 mg sec 300 mg bro 210 mg ixe 80 mg q2w>q4w bim 320b mg q4w>q8w til 100 mg til 200 mg gus 100 mg ris 150 mg n m a e st im at e d p a si 7 5 re sp on se r at e , % nonbiologic oral anti–tnf anti–il-12/23 anti–il-17 anti–il-23 b. 74.675.074.271.0 72.3 72.2 73.4 first-generation biologics second-generation biologics first-generation biologics second-generation biologics aadjusted for placebo response rates. bbim is not approved for use in the united states. note: posterior median value given for each therapy; error bars represent 95% cri. adm, adalimumab; apr, apremilast; bim, bimekizumab; biw, twice weekly; bro, brodalumab; cri, credible interval; deuc, deucravacitinib; etc, etanercept; gus, guselkumab; ifx, infl iximab; il, interleukin; ixe, ixekizumab; mtx, methotrexate; nma, network meta-analysis; pasi, psoriasis area and severity index; pbo, placebo; q2w, once every 2 weeks; q4w, once every 4 weeks; q8w, once every 8 weeks; ris, risankizumab; sec, secukinumab; til, tildrakizumab; tnf, tumor necrosis factor; ust, ustekinumab. conclusions • among oral nonbiologic treatments, deucravacitinib provided the best efficacy across time points compared with methotrexate and apremilast • the pasi 75 response rates for deucravacitinib were within the range of those for first-generation biologics at weeks 10–16 and 24–28 • at 1 year, the pasi 75 response rate for deucravacitinib was similar to that of adalimumab and ustekinumab • the psoriasis treatment paradigm is changing with the approval of deucravacitinib, a convenient oral therapy with a long-term effi cacy level similar to that of some biologic therapies references 1. guideline on missing data in confirmatory clinical trials. european medicines agency; 2010. https://www.ema.europa.eu/en/documents/ scientifi c-guideline/guideline-missing-data-confi rmatory-clinical-trials_ en.pdf 2. guidance for sponsors, clinical investigators, and irbs. us food and drug administration; 2008. http://www.fda.gov/downloads/ regulatoryinformation/guidances/ucm126489.pdf 3. page mj, et al. plos med. 2021;18:e1003583. acknowledgments • this study was sponsored by bristol myers squibb • medical writing and editorial assistance was provided by cheryl jones of peloton advantage, llc, an open health company, and funded by bristol myers squibb disclosures • aa: grants and personal fees: abbvie, bristol myers squibb, eli lilly, janssen, leo pharma, and novartis; personal fees: boehringer ingelheim/parexel, celgene, dermavant, genentech, glaxosmithkline, menlo therapeutics, merck, modernizing medicine, ortho dermatologics, pfizer, regeneron, sanofi genzyme, science 37, sun pharma, and valeant; grants: dermira, kyowa hakko kirin, and ucb, outside the submitted work • rbw: research grants: abbvie, almirall, amgen, celgene, eli lilly, janssen, leo pharma, novartis, pfizer, and ucb; consulting fees: abbvie, almirall, amgen, biogen, boehringer ingelheim, celgene, dice, eli lilly, janssen, leo pharma, novartis, pfizer, sanofi, ucb, and union • yz, jz, rk, and cd: employees of and may own stock options in bristol myers squibb • ac, ak, dj, and tw: employed by evidera, a company that provides consulting and other research services to bristol myers squibb • ma: advisory boards: abbvie, amgen, boehringer ingelheim, janssen biotech, and leo pharma; consulting fees: abbvie, amgen, eli lilly, janssen biotech, leo pharma, novartis, sun pharma, and ucb; honoraria: abbvie, amgen, boehringer ingelheim, eli lilly, janssen biotech, leo pharma, novartis, sun pharma, and ucb; investigator: abbvie, amgen, boehringer ingelheim, celgene, eli lilly, janssen biotech, leo pharma, merck, novartis, sun pharma, and ucb; research grants: abbvie, amgen, boehringer ingelheim, celgene, janssen biotech, leo pharma, merck, and sun pharma; speaker: abbvie, amgen, janssen biotech, leo pharma, sun pharma, and ucb indirect comparison of the short-, mid-, and long-term efficacy of treatments for moderate to severe plaque psoriasis: a systematic review and network meta-analysis april armstrong,1 richard b. warren,2 yichen zhong,3 joe zhuo,3 allie cichewicz,4 ananth kadambi,4 daniela r. junqueira,4 tracy westley,4 renata kisa,3 carolin daamen,3 matthias augustin5 1university of southern california, los angeles, ca; 2the university of manchester, manchester, uk; 3bristol myers squibb, princeton, nj; 4evidera, bethesda, md; 5university medical center, hamburg, germany presented at the fall clinical dermatology conference; october 20–23, 2022; las vegas, nv this poster may not be reproduced without written permission from the authors.email for april armstrong, md, mph: aprilarmstrong@post.harvard.edu scientifi c content on demand to request a copy of this poster: scan qr code via a barcode reader application qr codes are valid for 30 days after congress presentation date synopsis • patients with moderate to severe plaque psoriasis have several systemic treatment choices available, including oral nonbiologic and biologic options • deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 (tyk2) inhibitor, demonstrated superior effi cacy versus apremilast and placebo in two phase 3 randomized controlled trials (rcts) and is approved by the us food and drug administration for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy • this systematic literature review (slr) and network meta-analysis (nma) indirectly compared the efficacy of deucravacitinib with that of other approved, relevant systemic biologic and nonbiologic treatments over short-, medium-, and long-term follow-up; multinomial random effects models estimated improvement in responses on the psoriasis area and severity index (pasi) at weeks 10−16, 24−28, and 44−60 • pasi 75 (75% improvement in pasi) response rate with deucravacitinib was comparable to that of first-generation biologics at week 16, and higher at week 24; at week 52, it was comparable to that of the most effective fi rstgeneration biologics objective • the objective of this analysis was to examine the clinical effi cacy associated with deucravacitinib and other selected active biologic and nonbiologic treatments in patients with moderate to severe psoriasis methods • electronic databases were searched through october 2021 for rcts of systemic treatments in adults with moderate to severe psoriasis who reported improvement in response on pasi • phase 3 trial data were included when: — nonresponder imputation was applied1,2 — studies were conducted in multiple or single countries with diverse ethnic representation • nma was performed using multinomial random effects models adjusting for baseline risk (ie, placebo response) to estimate pasi responses over short-, mid-, and long-term follow-up periods (weeks 10−16, 24−28, and 44−60, respectively) and reported following the prisma reporting guidelines for meta-analysis3 results • the slr identifi ed 47 phase 3 rcts that applied nonresponder imputation and were included in the nma (figure 1 and figure 2a); the mid-term analysis included 28 studies (figure 2b); the long-term analysis included 21 studies (figure 2c) figure 1. prisma flow diagram full-text articles excluded (n = 446) • duplicates (n = 11) • publication type not of interest (n = 17) • study design not of interest (n = 25) • population not of interest (n = 60) • intervention/comparator not of interest (n = 105) • outcomes not of interest (n = 189) • relevant slrs/nmas published 2019-2020 (n = 39) records excluded by title and abstract screening (n = 3632) full-text articles assessed for eligibility (n = 818) 251 rct publications and 132 pooleda analyses included in slr duplicates removed (n = 3037) rcts included in global pasi nma (n = 96 unique rcts)b records screened (n = 4450) rcts included in phase 3 global nri pasi nma (n = 47 unique rcts)b id e n ti fi ca ti o n sc re e n in g e li gi b il it y in cl u d e d records identified through database searching (n = 7487) records identified through other sources (conference proceedings: n = 11) apooled analyses of rcts were not included in the slr unless unique data were available that were not published elsewhere. brcts eligible for global pasi nma and phase 3 global nri pasi nma, including poetyk ps0-1 and poetyk pso-2. nma, network meta-analysis; nri, nonresponder imputation; pasi, psoriasis area and severity index; rct, randomized controlled trial; slr, systematic literature review. figure 2. network plots of trials included in the shortterm (10–16 weeks; a), mid-term (24–28 weeks; b), and long-term (44–60 weeks; c) analyses v etanercept study group liberate etanercept study group etanercept study group fixture m10-114 m10-315 opt compare study resurface 2 uncover 2, 3 liberate esteem 1, 2 liberate poetyk 1, 2poetyk 1, 2 fixture poetyk 1, 2 uncover 2, 3 uncover 1, 2, 3 erasure feature fixture juncture allure erasure feature fixture juncture amagine 2, 3 be vivid ultimma-1, -2 amagine 1, 2, 3 amagine 2, 3 clear immerge be vivid be radiant be ready be vivid orion voyage 1, 2 voyage 1, 2 be sure immvent voyage 1, 2 reveal champion express express ii spirit restore 1 resurface 1, 2 resurface 1, 2 phoenix 1, 2 resurface 1, 2 resurface 2 accept ust 90 mg til 200 mg til 100 mg ifx 5 mg/kg mtx 7.5 to 25 mg adm 40 mggus 100 mg bim 320 mg ust 45 or 90 mg sec 300 mg sec 150 mg apr 30 mg etc 25 mg biw etc 50 mg biw deuc 6 mg ixe 80 mg q2w bro 210 mg ris 150 mg pbo resurface 2 fixture reich, 2020 champion champion metop eclipse blauvelt, 2021 immhance ultimma-1, -2 ultimma-1, -2 ixora-5 erasure feature fixture juncture a. erasure feature fixture juncture erasure feature fixture juncture erasure feature fixture juncture amagine 2, 3 be vivid ultimma-1, -2 ultimma-1, -2 ultimma-1, -2 poetyk 1 uncover 3 amagine 2, 3 amagine 2, 3 immerge be radiant voyage 1 voyage 1 voyage 1 express express ii fixture fixturefixture metop eclipseixora-5 ifx 5 mg/kg mtx 7.5 to 25 mg adm 40 mggus 100 mg bim 320 mg ust 45 or 90 mg sec 300 mg sec 150 mg apr 30 mg etc 50 mg biw deuc 6 mg ixe 80 mg q2w bro 210 mg ris 150 mg pbo liberate clear c. etanercept study group etanercept study group esteem 1, 2 poetyk 1, 2poetyk 1, 2 fixture poetyk 1, 2 uncover 3 erasure feature fixture erasure feature fixture allure erasure feature fixture amagine 2, 3 be vivid amagine 1, 2, 3 amagine 2, 3 clear immhance immerge be radiant orion voyage 1, 2 voyage 1, 2 voyage 1, 2 be sure express express ii resurface 1, 2 resurface 1, 2 phoenix 1, 2 resurface 2 ust 90 mg til 200 mg til 100 mg ifx 5 mg/kg mtx 7.5 to 25 mg adm 40 mggus 100 mg bim 320 mg ust 45 or 90 mg sec 300 mg sec 150 mg apr 30 mg etc 25 mg biw etc 50 mg biw deuc 6 mg ixe 80 mg q2w bro 210 mg ris 150 mg pbo resurface 2 fixture metop eclipse ixora-5 resurface 1, 2 b. etanercept study group fixture resurface 2 act, acitretin; adm, adalimumab; apr, apremilast; bim, bimekizumab; biw, twice weekly; bro, brodalumab; deuc, deucravacitinib; etc, etanercept; gus, guselkumab; ifx, infl iximab; ixe, ixekizumab; mtx, methotrexate; pbo, placebo; ris, risankizumab; q2w, once every 2 weeks; sec, secukinumab; til, tildrakizumab; ust, ustekinumab. • pasi 75 response rate with deucravacitinib at week 16 (54.1%; credible interval [crl], 46.5%, 61.6%) was within range of the first-generation biologics (range, 39.7 [crl, 31.6%, 48.3%] for etanercept 25 mg to 79.0% [crl, 74.0%, 83.5%] for infl iximab; figure 3a) • pasi 75 response with deucravacitinib increased at week 24 to 63.3% (crl, 58.0%, 68.4%; figure 3b) • at week 52, the pasi 75 response rate for deucravacitinib (65.9%; crl, 58.0%, 73.4%) was comparable to that of the most effective first-generation biologics — adalimumab (62.8%; crl, 55.3%, 69.6%) and ustekinumab (68.0%; crl, 64.6%, 71.5%; figure 3c) • newer il-17 and il-23 inhibitors showed the highest pasi 75 response rates of the included treatments, across all time points figure 3. short-term estimated pasi 75 response,a posterior median and 95% cri. weeks 10–16 (a), midterm estimated pasi 75 response for weeks 24–28 (b), and long-term estimated pasi 75 response for weeks 44–60 (c) 56.7 ifx 5 mg/kg adm 40 mg 62.8 48.4 apr 30 mg 45.0 mtx ust 90 mg 70.9 ust 45 or 90 mg 71.1 5.8 33.5 40.1 54.1 39.7 49.8 71.7 79.0 84.8 85.7 89.0 93.0 63.0 64.2 87.8 89.6 0 10 20 30 40 50 60 70 80 90 100 pbo apr 30 mg mtx deuc 6 mg etc 25 mg biw/50 mg qw etc 50 mg biw adm 40 mg ifx 5 mg/kg sec 150 mg sec 300 mg bro 210 mg ixe 80 mg q2w bim 320b mg til 100 mg til 200 mg gus 100 mg ris 150 mg n m a e st im at e d p a si 7 5 re sp on se r at e , % nonbiologic oral anti-tnf anti–il-12/23 anti–il-17 anti–il-23 first-generation biologics second-generation biologics a. 71.3 6.4 54.0 77.0 81.0 83.9 86.4 87.8 91.6 0 10 20 30 40 50 60 70 80 90 100 pbo deuc 6 mg etc 50 mg biw ust 45 or 90 mg sec 150 mg sec 300 mg bro 210 mg ixe 80 mg q2w>q4w bim 320b mg q4w>q8w gus 100 mg ris 150 mg n m a e st im at e d p a si 7 5 re sp on se r at e , % nonbiologic oral anti-tnf anti–il–12/23 anti–il-17 anti–il-23 c. 62.1 68.0 65.9 6.4 34.8 50.1 63.3 43.7 54.4 84.7 86.2 89.6 92.1 89.5 93.8 0 10 20 30 40 50 60 70 80 90 100 pbo apr 30 mg mtx deuc 6 mg etc 25 mg biw/50 mg qw etc 50 mg biw adm 40 mg ifx 5 mg/kg ust 45 or 90 mg ust 90 mg sec 150 mg sec 300 mg bro 210 mg ixe 80 mg q2w>q4w bim 320b mg q4w>q8w til 100 mg til 200 mg gus 100 mg ris 150 mg n m a e st im at e d p a si 7 5 re sp on se r at e , % nonbiologic oral anti–tnf anti–il-12/23 anti–il-17 anti–il-23 b. 74.675.074.271.0 72.3 72.2 73.4 first-generation biologics second-generation biologics first-generation biologics second-generation biologics aadjusted for placebo response rates. bbim is not approved for use in the united states. note: posterior median value given for each therapy; error bars represent 95% cri. adm, adalimumab; apr, apremilast; bim, bimekizumab; biw, twice weekly; bro, brodalumab; cri, credible interval; deuc, deucravacitinib; etc, etanercept; gus, guselkumab; ifx, infl iximab; il, interleukin; ixe, ixekizumab; mtx, methotrexate; nma, network meta-analysis; pasi, psoriasis area and severity index; pbo, placebo; q2w, once every 2 weeks; q4w, once every 4 weeks; q8w, once every 8 weeks; ris, risankizumab; sec, secukinumab; til, tildrakizumab; tnf, tumor necrosis factor; ust, ustekinumab. conclusions • among oral nonbiologic treatments, deucravacitinib provided the best efficacy across time points compared with methotrexate and apremilast • the pasi 75 response rates for deucravacitinib were within the range of those for first-generation biologics at weeks 10–16 and 24–28 • at 1 year, the pasi 75 response rate for deucravacitinib was similar to that of adalimumab and ustekinumab • the psoriasis treatment paradigm is changing with the approval of deucravacitinib, a convenient oral therapy with a long-term effi cacy level similar to that of some biologic therapies references 1. guideline on missing data in confirmatory clinical trials. european medicines agency; 2010. https://www.ema.europa.eu/en/documents/ scientifi c-guideline/guideline-missing-data-confi rmatory-clinical-trials_ en.pdf 2. guidance for sponsors, clinical investigators, and irbs. us food and drug administration; 2008. http://www.fda.gov/downloads/ regulatoryinformation/guidances/ucm126489.pdf 3. page mj, et al. plos med. 2021;18:e1003583. acknowledgments • this study was sponsored by bristol myers squibb • medical writing and editorial assistance was provided by cheryl jones of peloton advantage, llc, an open health company, and funded by bristol myers squibb disclosures • aa: grants and personal fees: abbvie, bristol myers squibb, eli lilly, janssen, leo pharma, and novartis; personal fees: boehringer ingelheim/parexel, celgene, dermavant, genentech, glaxosmithkline, menlo therapeutics, merck, modernizing medicine, ortho dermatologics, pfizer, regeneron, sanofi genzyme, science 37, sun pharma, and valeant; grants: dermira, kyowa hakko kirin, and ucb, outside the submitted work • rbw: research grants: abbvie, almirall, amgen, celgene, eli lilly, janssen, leo pharma, novartis, pfizer, and ucb; consulting fees: abbvie, almirall, amgen, biogen, boehringer ingelheim, celgene, dice, eli lilly, janssen, leo pharma, novartis, pfizer, sanofi, ucb, and union • yz, jz, rk, and cd: employees of and may own stock options in bristol myers squibb • ac, ak, dj, and tw: employed by evidera, a company that provides consulting and other research services to bristol myers squibb • ma: advisory boards: abbvie, amgen, boehringer ingelheim, janssen biotech, and leo pharma; consulting fees: abbvie, amgen, eli lilly, janssen biotech, leo pharma, novartis, sun pharma, and ucb; honoraria: abbvie, amgen, boehringer ingelheim, eli lilly, janssen biotech, leo pharma, novartis, sun pharma, and ucb; investigator: abbvie, amgen, boehringer ingelheim, celgene, eli lilly, janssen biotech, leo pharma, merck, novartis, sun pharma, and ucb; research grants: abbvie, amgen, boehringer ingelheim, celgene, janssen biotech, leo pharma, merck, and sun pharma; speaker: abbvie, amgen, janssen biotech, leo pharma, sun pharma, and ucb indirect comparison of the short-, mid-, and long-term efficacy of treatments for moderate to severe plaque psoriasis: a systematic review and network meta-analysis april armstrong,1 richard b. warren,2 yichen zhong,3 joe zhuo,3 allie cichewicz,4 ananth kadambi,4 daniela r. junqueira,4 tracy westley,4 renata kisa,3 carolin daamen,3 matthias augustin5 1university of southern california, los angeles, ca; 2the university of manchester, manchester, uk; 3bristol myers squibb, princeton, nj; 4evidera, bethesda, md; 5university medical center, hamburg, germany presented at the fall clinical dermatology conference; october 20–23, 2022; las vegas, nv this poster may not be reproduced without written permission from the authors.email for april armstrong, md, mph: aprilarmstrong@post.harvard.edu scientifi c content on demand to request a copy of this poster: scan qr code via a barcode reader application qr codes are valid for 30 days after congress presentation date synopsis • patients with moderate to severe plaque psoriasis have several systemic treatment choices available, including oral nonbiologic and biologic options • deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 (tyk2) inhibitor, demonstrated superior effi cacy versus apremilast and placebo in two phase 3 randomized controlled trials (rcts) and is approved by the us food and drug administration for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy • this systematic literature review (slr) and network meta-analysis (nma) indirectly compared the efficacy of deucravacitinib with that of other approved, relevant systemic biologic and nonbiologic treatments over short-, medium-, and long-term follow-up; multinomial random effects models estimated improvement in responses on the psoriasis area and severity index (pasi) at weeks 10−16, 24−28, and 44−60 • pasi 75 (75% improvement in pasi) response rate with deucravacitinib was comparable to that of first-generation biologics at week 16, and higher at week 24; at week 52, it was comparable to that of the most effective fi rstgeneration biologics objective • the objective of this analysis was to examine the clinical effi cacy associated with deucravacitinib and other selected active biologic and nonbiologic treatments in patients with moderate to severe psoriasis methods • electronic databases were searched through october 2021 for rcts of systemic treatments in adults with moderate to severe psoriasis who reported improvement in response on pasi • phase 3 trial data were included when: — nonresponder imputation was applied1,2 — studies were conducted in multiple or single countries with diverse ethnic representation • nma was performed using multinomial random effects models adjusting for baseline risk (ie, placebo response) to estimate pasi responses over short-, mid-, and long-term follow-up periods (weeks 10−16, 24−28, and 44−60, respectively) and reported following the prisma reporting guidelines for meta-analysis3 results • the slr identifi ed 47 phase 3 rcts that applied nonresponder imputation and were included in the nma (figure 1 and figure 2a); the mid-term analysis included 28 studies (figure 2b); the long-term analysis included 21 studies (figure 2c) figure 1. prisma flow diagram full-text articles excluded (n = 446) • duplicates (n = 11) • publication type not of interest (n = 17) • study design not of interest (n = 25) • population not of interest (n = 60) • intervention/comparator not of interest (n = 105) • outcomes not of interest (n = 189) • relevant slrs/nmas published 2019-2020 (n = 39) records excluded by title and abstract screening (n = 3632) full-text articles assessed for eligibility (n = 818) 251 rct publications and 132 pooleda analyses included in slr duplicates removed (n = 3037) rcts included in global pasi nma (n = 96 unique rcts)b records screened (n = 4450) rcts included in phase 3 global nri pasi nma (n = 47 unique rcts)b id e n ti fi ca ti o n sc re e n in g e li gi b il it y in cl u d e d records identified through database searching (n = 7487) records identified through other sources (conference proceedings: n = 11) apooled analyses of rcts were not included in the slr unless unique data were available that were not published elsewhere. brcts eligible for global pasi nma and phase 3 global nri pasi nma, including poetyk ps0-1 and poetyk pso-2. nma, network meta-analysis; nri, nonresponder imputation; pasi, psoriasis area and severity index; rct, randomized controlled trial; slr, systematic literature review. figure 2. network plots of trials included in the shortterm (10–16 weeks; a), mid-term (24–28 weeks; b), and long-term (44–60 weeks; c) analyses v etanercept study group liberate etanercept study group etanercept study group fixture m10-114 m10-315 opt compare study resurface 2 uncover 2, 3 liberate esteem 1, 2 liberate poetyk 1, 2poetyk 1, 2 fixture poetyk 1, 2 uncover 2, 3 uncover 1, 2, 3 erasure feature fixture juncture allure erasure feature fixture juncture amagine 2, 3 be vivid ultimma-1, -2 amagine 1, 2, 3 amagine 2, 3 clear immerge be vivid be radiant be ready be vivid orion voyage 1, 2 voyage 1, 2 be sure immvent voyage 1, 2 reveal champion express express ii spirit restore 1 resurface 1, 2 resurface 1, 2 phoenix 1, 2 resurface 1, 2 resurface 2 accept ust 90 mg til 200 mg til 100 mg ifx 5 mg/kg mtx 7.5 to 25 mg adm 40 mggus 100 mg bim 320 mg ust 45 or 90 mg sec 300 mg sec 150 mg apr 30 mg etc 25 mg biw etc 50 mg biw deuc 6 mg ixe 80 mg q2w bro 210 mg ris 150 mg pbo resurface 2 fixture reich, 2020 champion champion metop eclipse blauvelt, 2021 immhance ultimma-1, -2 ultimma-1, -2 ixora-5 erasure feature fixture juncture a. erasure feature fixture juncture erasure feature fixture juncture erasure feature fixture juncture amagine 2, 3 be vivid ultimma-1, -2 ultimma-1, -2 ultimma-1, -2 poetyk 1 uncover 3 amagine 2, 3 amagine 2, 3 immerge be radiant voyage 1 voyage 1 voyage 1 express express ii fixture fixturefixture metop eclipseixora-5 ifx 5 mg/kg mtx 7.5 to 25 mg adm 40 mggus 100 mg bim 320 mg ust 45 or 90 mg sec 300 mg sec 150 mg apr 30 mg etc 50 mg biw deuc 6 mg ixe 80 mg q2w bro 210 mg ris 150 mg pbo liberate clear c. etanercept study group etanercept study group esteem 1, 2 poetyk 1, 2poetyk 1, 2 fixture poetyk 1, 2 uncover 3 erasure feature fixture erasure feature fixture allure erasure feature fixture amagine 2, 3 be vivid amagine 1, 2, 3 amagine 2, 3 clear immhance immerge be radiant orion voyage 1, 2 voyage 1, 2 voyage 1, 2 be sure express express ii resurface 1, 2 resurface 1, 2 phoenix 1, 2 resurface 2 ust 90 mg til 200 mg til 100 mg ifx 5 mg/kg mtx 7.5 to 25 mg adm 40 mggus 100 mg bim 320 mg ust 45 or 90 mg sec 300 mg sec 150 mg apr 30 mg etc 25 mg biw etc 50 mg biw deuc 6 mg ixe 80 mg q2w bro 210 mg ris 150 mg pbo resurface 2 fixture metop eclipse ixora-5 resurface 1, 2 b. etanercept study group fixture resurface 2 act, acitretin; adm, adalimumab; apr, apremilast; bim, bimekizumab; biw, twice weekly; bro, brodalumab; deuc, deucravacitinib; etc, etanercept; gus, guselkumab; ifx, infl iximab; ixe, ixekizumab; mtx, methotrexate; pbo, placebo; ris, risankizumab; q2w, once every 2 weeks; sec, secukinumab; til, tildrakizumab; ust, ustekinumab. • pasi 75 response rate with deucravacitinib at week 16 (54.1%; credible interval [crl], 46.5%, 61.6%) was within range of the first-generation biologics (range, 39.7 [crl, 31.6%, 48.3%] for etanercept 25 mg to 79.0% [crl, 74.0%, 83.5%] for infl iximab; figure 3a) • pasi 75 response with deucravacitinib increased at week 24 to 63.3% (crl, 58.0%, 68.4%; figure 3b) • at week 52, the pasi 75 response rate for deucravacitinib (65.9%; crl, 58.0%, 73.4%) was comparable to that of the most effective first-generation biologics — adalimumab (62.8%; crl, 55.3%, 69.6%) and ustekinumab (68.0%; crl, 64.6%, 71.5%; figure 3c) • newer il-17 and il-23 inhibitors showed the highest pasi 75 response rates of the included treatments, across all time points figure 3. short-term estimated pasi 75 response,a posterior median and 95% cri. weeks 10–16 (a), midterm estimated pasi 75 response for weeks 24–28 (b), and long-term estimated pasi 75 response for weeks 44–60 (c) 56.7 ifx 5 mg/kg adm 40 mg 62.8 48.4 apr 30 mg 45.0 mtx ust 90 mg 70.9 ust 45 or 90 mg 71.1 5.8 33.5 40.1 54.1 39.7 49.8 71.7 79.0 84.8 85.7 89.0 93.0 63.0 64.2 87.8 89.6 0 10 20 30 40 50 60 70 80 90 100 pbo apr 30 mg mtx deuc 6 mg etc 25 mg biw/50 mg qw etc 50 mg biw adm 40 mg ifx 5 mg/kg sec 150 mg sec 300 mg bro 210 mg ixe 80 mg q2w bim 320b mg til 100 mg til 200 mg gus 100 mg ris 150 mg n m a e st im at e d p a si 7 5 re sp on se r at e , % nonbiologic oral anti-tnf anti–il-12/23 anti–il-17 anti–il-23 first-generation biologics second-generation biologics a. 71.3 6.4 54.0 77.0 81.0 83.9 86.4 87.8 91.6 0 10 20 30 40 50 60 70 80 90 100 pbo deuc 6 mg etc 50 mg biw ust 45 or 90 mg sec 150 mg sec 300 mg bro 210 mg ixe 80 mg q2w>q4w bim 320b mg q4w>q8w gus 100 mg ris 150 mg n m a e st im at e d p a si 7 5 re sp on se r at e , % nonbiologic oral anti-tnf anti–il–12/23 anti–il-17 anti–il-23 c. 62.1 68.0 65.9 6.4 34.8 50.1 63.3 43.7 54.4 84.7 86.2 89.6 92.1 89.5 93.8 0 10 20 30 40 50 60 70 80 90 100 pbo apr 30 mg mtx deuc 6 mg etc 25 mg biw/50 mg qw etc 50 mg biw adm 40 mg ifx 5 mg/kg ust 45 or 90 mg ust 90 mg sec 150 mg sec 300 mg bro 210 mg ixe 80 mg q2w>q4w bim 320b mg q4w>q8w til 100 mg til 200 mg gus 100 mg ris 150 mg n m a e st im at e d p a si 7 5 re sp on se r at e , % nonbiologic oral anti–tnf anti–il-12/23 anti–il-17 anti–il-23 b. 74.675.074.271.0 72.3 72.2 73.4 first-generation biologics second-generation biologics first-generation biologics second-generation biologics aadjusted for placebo response rates. bbim is not approved for use in the united states. note: posterior median value given for each therapy; error bars represent 95% cri. adm, adalimumab; apr, apremilast; bim, bimekizumab; biw, twice weekly; bro, brodalumab; cri, credible interval; deuc, deucravacitinib; etc, etanercept; gus, guselkumab; ifx, infl iximab; il, interleukin; ixe, ixekizumab; mtx, methotrexate; nma, network meta-analysis; pasi, psoriasis area and severity index; pbo, placebo; q2w, once every 2 weeks; q4w, once every 4 weeks; q8w, once every 8 weeks; ris, risankizumab; sec, secukinumab; til, tildrakizumab; tnf, tumor necrosis factor; ust, ustekinumab. conclusions • among oral nonbiologic treatments, deucravacitinib provided the best efficacy across time points compared with methotrexate and apremilast • the pasi 75 response rates for deucravacitinib were within the range of those for first-generation biologics at weeks 10–16 and 24–28 • at 1 year, the pasi 75 response rate for deucravacitinib was similar to that of adalimumab and ustekinumab • the psoriasis treatment paradigm is changing with the approval of deucravacitinib, a convenient oral therapy with a long-term effi cacy level similar to that of some biologic therapies references 1. guideline on missing data in confirmatory clinical trials. european medicines agency; 2010. https://www.ema.europa.eu/en/documents/ scientifi c-guideline/guideline-missing-data-confi rmatory-clinical-trials_ en.pdf 2. guidance for sponsors, clinical investigators, and irbs. us food and drug administration; 2008. http://www.fda.gov/downloads/ regulatoryinformation/guidances/ucm126489.pdf 3. page mj, et al. plos med. 2021;18:e1003583. acknowledgments • this study was sponsored by bristol myers squibb • medical writing and editorial assistance was provided by cheryl jones of peloton advantage, llc, an open health company, and funded by bristol myers squibb disclosures • aa: grants and personal fees: abbvie, bristol myers squibb, eli lilly, janssen, leo pharma, and novartis; personal fees: boehringer ingelheim/parexel, celgene, dermavant, genentech, glaxosmithkline, menlo therapeutics, merck, modernizing medicine, ortho dermatologics, pfizer, regeneron, sanofi genzyme, science 37, sun pharma, and valeant; grants: dermira, kyowa hakko kirin, and ucb, outside the submitted work • rbw: research grants: abbvie, almirall, amgen, celgene, eli lilly, janssen, leo pharma, novartis, pfizer, and ucb; consulting fees: abbvie, almirall, amgen, biogen, boehringer ingelheim, celgene, dice, eli lilly, janssen, leo pharma, novartis, pfizer, sanofi, ucb, and union • yz, jz, rk, and cd: employees of and may own stock options in bristol myers squibb • ac, ak, dj, and tw: employed by evidera, a company that provides consulting and other research services to bristol myers squibb • ma: advisory boards: abbvie, amgen, boehringer ingelheim, janssen biotech, and leo pharma; consulting fees: abbvie, amgen, eli lilly, janssen biotech, leo pharma, novartis, sun pharma, and ucb; honoraria: abbvie, amgen, boehringer ingelheim, eli lilly, janssen biotech, leo pharma, novartis, sun pharma, and ucb; investigator: abbvie, amgen, boehringer ingelheim, celgene, eli lilly, janssen biotech, leo pharma, merck, novartis, sun pharma, and ucb; research grants: abbvie, amgen, boehringer ingelheim, celgene, janssen biotech, leo pharma, merck, and sun pharma; speaker: abbvie, amgen, janssen biotech, leo pharma, sun pharma, and ucb indirect comparison of the short-, mid-, and long-term efficacy of treatments for moderate to severe plaque psoriasis: a systematic review and network meta-analysis april armstrong,1 richard b. warren,2 yichen zhong,3 joe zhuo,3 allie cichewicz,4 ananth kadambi,4 daniela r. junqueira,4 tracy westley,4 renata kisa,3 carolin daamen,3 matthias augustin5 1university of southern california, los angeles, ca; 2the university of manchester, manchester, uk; 3bristol myers squibb, princeton, nj; 4evidera, bethesda, md; 5university medical center, hamburg, germany presented at the fall clinical dermatology conference; october 20–23, 2022; las vegas, nv this poster may not be reproduced without written permission from the authors.email for april armstrong, md, mph: aprilarmstrong@post.harvard.edu scientifi c content on demand to request a copy of this poster: scan qr code via a barcode reader application qr codes are valid for 30 days after congress presentation date synopsis • patients with moderate to severe plaque psoriasis have several systemic treatment choices available, including oral nonbiologic and biologic options • deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 (tyk2) inhibitor, demonstrated superior effi cacy versus apremilast and placebo in two phase 3 randomized controlled trials (rcts) and is approved by the us food and drug administration for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy • this systematic literature review (slr) and network meta-analysis (nma) indirectly compared the efficacy of deucravacitinib with that of other approved, relevant systemic biologic and nonbiologic treatments over short-, medium-, and long-term follow-up; multinomial random effects models estimated improvement in responses on the psoriasis area and severity index (pasi) at weeks 10−16, 24−28, and 44−60 • pasi 75 (75% improvement in pasi) response rate with deucravacitinib was comparable to that of first-generation biologics at week 16, and higher at week 24; at week 52, it was comparable to that of the most effective fi rstgeneration biologics objective • the objective of this analysis was to examine the clinical effi cacy associated with deucravacitinib and other selected active biologic and nonbiologic treatments in patients with moderate to severe psoriasis methods • electronic databases were searched through october 2021 for rcts of systemic treatments in adults with moderate to severe psoriasis who reported improvement in response on pasi • phase 3 trial data were included when: — nonresponder imputation was applied1,2 — studies were conducted in multiple or single countries with diverse ethnic representation • nma was performed using multinomial random effects models adjusting for baseline risk (ie, placebo response) to estimate pasi responses over short-, mid-, and long-term follow-up periods (weeks 10−16, 24−28, and 44−60, respectively) and reported following the prisma reporting guidelines for meta-analysis3 results • the slr identifi ed 47 phase 3 rcts that applied nonresponder imputation and were included in the nma (figure 1 and figure 2a); the mid-term analysis included 28 studies (figure 2b); the long-term analysis included 21 studies (figure 2c) figure 1. prisma flow diagram full-text articles excluded (n = 446) • duplicates (n = 11) • publication type not of interest (n = 17) • study design not of interest (n = 25) • population not of interest (n = 60) • intervention/comparator not of interest (n = 105) • outcomes not of interest (n = 189) • relevant slrs/nmas published 2019-2020 (n = 39) records excluded by title and abstract screening (n = 3632) full-text articles assessed for eligibility (n = 818) 251 rct publications and 132 pooleda analyses included in slr duplicates removed (n = 3037) rcts included in global pasi nma (n = 96 unique rcts)b records screened (n = 4450) rcts included in phase 3 global nri pasi nma (n = 47 unique rcts)b id e n ti fi ca ti o n sc re e n in g e li gi b il it y in cl u d e d records identified through database searching (n = 7487) records identified through other sources (conference proceedings: n = 11) apooled analyses of rcts were not included in the slr unless unique data were available that were not published elsewhere. brcts eligible for global pasi nma and phase 3 global nri pasi nma, including poetyk ps0-1 and poetyk pso-2. nma, network meta-analysis; nri, nonresponder imputation; pasi, psoriasis area and severity index; rct, randomized controlled trial; slr, systematic literature review. figure 2. network plots of trials included in the shortterm (10–16 weeks; a), mid-term (24–28 weeks; b), and long-term (44–60 weeks; c) analyses v etanercept study group liberate etanercept study group etanercept study group fixture m10-114 m10-315 opt compare study resurface 2 uncover 2, 3 liberate esteem 1, 2 liberate poetyk 1, 2poetyk 1, 2 fixture poetyk 1, 2 uncover 2, 3 uncover 1, 2, 3 erasure feature fixture juncture allure erasure feature fixture juncture amagine 2, 3 be vivid ultimma-1, -2 amagine 1, 2, 3 amagine 2, 3 clear immerge be vivid be radiant be ready be vivid orion voyage 1, 2 voyage 1, 2 be sure immvent voyage 1, 2 reveal champion express express ii spirit restore 1 resurface 1, 2 resurface 1, 2 phoenix 1, 2 resurface 1, 2 resurface 2 accept ust 90 mg til 200 mg til 100 mg ifx 5 mg/kg mtx 7.5 to 25 mg adm 40 mggus 100 mg bim 320 mg ust 45 or 90 mg sec 300 mg sec 150 mg apr 30 mg etc 25 mg biw etc 50 mg biw deuc 6 mg ixe 80 mg q2w bro 210 mg ris 150 mg pbo resurface 2 fixture reich, 2020 champion champion metop eclipse blauvelt, 2021 immhance ultimma-1, -2 ultimma-1, -2 ixora-5 erasure feature fixture juncture a. erasure feature fixture juncture erasure feature fixture juncture erasure feature fixture juncture amagine 2, 3 be vivid ultimma-1, -2 ultimma-1, -2 ultimma-1, -2 poetyk 1 uncover 3 amagine 2, 3 amagine 2, 3 immerge be radiant voyage 1 voyage 1 voyage 1 express express ii fixture fixturefixture metop eclipseixora-5 ifx 5 mg/kg mtx 7.5 to 25 mg adm 40 mggus 100 mg bim 320 mg ust 45 or 90 mg sec 300 mg sec 150 mg apr 30 mg etc 50 mg biw deuc 6 mg ixe 80 mg q2w bro 210 mg ris 150 mg pbo liberate clear c. etanercept study group etanercept study group esteem 1, 2 poetyk 1, 2poetyk 1, 2 fixture poetyk 1, 2 uncover 3 erasure feature fixture erasure feature fixture allure erasure feature fixture amagine 2, 3 be vivid amagine 1, 2, 3 amagine 2, 3 clear immhance immerge be radiant orion voyage 1, 2 voyage 1, 2 voyage 1, 2 be sure express express ii resurface 1, 2 resurface 1, 2 phoenix 1, 2 resurface 2 ust 90 mg til 200 mg til 100 mg ifx 5 mg/kg mtx 7.5 to 25 mg adm 40 mggus 100 mg bim 320 mg ust 45 or 90 mg sec 300 mg sec 150 mg apr 30 mg etc 25 mg biw etc 50 mg biw deuc 6 mg ixe 80 mg q2w bro 210 mg ris 150 mg pbo resurface 2 fixture metop eclipse ixora-5 resurface 1, 2 b. etanercept study group fixture resurface 2 act, acitretin; adm, adalimumab; apr, apremilast; bim, bimekizumab; biw, twice weekly; bro, brodalumab; deuc, deucravacitinib; etc, etanercept; gus, guselkumab; ifx, infl iximab; ixe, ixekizumab; mtx, methotrexate; pbo, placebo; ris, risankizumab; q2w, once every 2 weeks; sec, secukinumab; til, tildrakizumab; ust, ustekinumab. • pasi 75 response rate with deucravacitinib at week 16 (54.1%; credible interval [crl], 46.5%, 61.6%) was within range of the first-generation biologics (range, 39.7 [crl, 31.6%, 48.3%] for etanercept 25 mg to 79.0% [crl, 74.0%, 83.5%] for infl iximab; figure 3a) • pasi 75 response with deucravacitinib increased at week 24 to 63.3% (crl, 58.0%, 68.4%; figure 3b) • at week 52, the pasi 75 response rate for deucravacitinib (65.9%; crl, 58.0%, 73.4%) was comparable to that of the most effective first-generation biologics — adalimumab (62.8%; crl, 55.3%, 69.6%) and ustekinumab (68.0%; crl, 64.6%, 71.5%; figure 3c) • newer il-17 and il-23 inhibitors showed the highest pasi 75 response rates of the included treatments, across all time points figure 3. short-term estimated pasi 75 response,a posterior median and 95% cri. weeks 10–16 (a), midterm estimated pasi 75 response for weeks 24–28 (b), and long-term estimated pasi 75 response for weeks 44–60 (c) 56.7 ifx 5 mg/kg adm 40 mg 62.8 48.4 apr 30 mg 45.0 mtx ust 90 mg 70.9 ust 45 or 90 mg 71.1 5.8 33.5 40.1 54.1 39.7 49.8 71.7 79.0 84.8 85.7 89.0 93.0 63.0 64.2 87.8 89.6 0 10 20 30 40 50 60 70 80 90 100 pbo apr 30 mg mtx deuc 6 mg etc 25 mg biw/50 mg qw etc 50 mg biw adm 40 mg ifx 5 mg/kg sec 150 mg sec 300 mg bro 210 mg ixe 80 mg q2w bim 320b mg til 100 mg til 200 mg gus 100 mg ris 150 mg n m a e st im at e d p a si 7 5 re sp on se r at e , % nonbiologic oral anti-tnf anti–il-12/23 anti–il-17 anti–il-23 first-generation biologics second-generation biologics a. 71.3 6.4 54.0 77.0 81.0 83.9 86.4 87.8 91.6 0 10 20 30 40 50 60 70 80 90 100 pbo deuc 6 mg etc 50 mg biw ust 45 or 90 mg sec 150 mg sec 300 mg bro 210 mg ixe 80 mg q2w>q4w bim 320b mg q4w>q8w gus 100 mg ris 150 mg n m a e st im at e d p a si 7 5 re sp on se r at e , % nonbiologic oral anti-tnf anti–il–12/23 anti–il-17 anti–il-23 c. 62.1 68.0 65.9 6.4 34.8 50.1 63.3 43.7 54.4 84.7 86.2 89.6 92.1 89.5 93.8 0 10 20 30 40 50 60 70 80 90 100 pbo apr 30 mg mtx deuc 6 mg etc 25 mg biw/50 mg qw etc 50 mg biw adm 40 mg ifx 5 mg/kg ust 45 or 90 mg ust 90 mg sec 150 mg sec 300 mg bro 210 mg ixe 80 mg q2w>q4w bim 320b mg q4w>q8w til 100 mg til 200 mg gus 100 mg ris 150 mg n m a e st im at e d p a si 7 5 re sp on se r at e , % nonbiologic oral anti–tnf anti–il-12/23 anti–il-17 anti–il-23 b. 74.675.074.271.0 72.3 72.2 73.4 first-generation biologics second-generation biologics first-generation biologics second-generation biologics aadjusted for placebo response rates. bbim is not approved for use in the united states. note: posterior median value given for each therapy; error bars represent 95% cri. adm, adalimumab; apr, apremilast; bim, bimekizumab; biw, twice weekly; bro, brodalumab; cri, credible interval; deuc, deucravacitinib; etc, etanercept; gus, guselkumab; ifx, infl iximab; il, interleukin; ixe, ixekizumab; mtx, methotrexate; nma, network meta-analysis; pasi, psoriasis area and severity index; pbo, placebo; q2w, once every 2 weeks; q4w, once every 4 weeks; q8w, once every 8 weeks; ris, risankizumab; sec, secukinumab; til, tildrakizumab; tnf, tumor necrosis factor; ust, ustekinumab. conclusions • among oral nonbiologic treatments, deucravacitinib provided the best efficacy across time points compared with methotrexate and apremilast • the pasi 75 response rates for deucravacitinib were within the range of those for first-generation biologics at weeks 10–16 and 24–28 • at 1 year, the pasi 75 response rate for deucravacitinib was similar to that of adalimumab and ustekinumab • the psoriasis treatment paradigm is changing with the approval of deucravacitinib, a convenient oral therapy with a long-term effi cacy level similar to that of some biologic therapies references 1. guideline on missing data in confirmatory clinical trials. european medicines agency; 2010. https://www.ema.europa.eu/en/documents/ scientifi c-guideline/guideline-missing-data-confi rmatory-clinical-trials_ en.pdf 2. guidance for sponsors, clinical investigators, and irbs. us food and drug administration; 2008. http://www.fda.gov/downloads/ regulatoryinformation/guidances/ucm126489.pdf 3. page mj, et al. plos med. 2021;18:e1003583. acknowledgments • this study was sponsored by bristol myers squibb • medical writing and editorial assistance was provided by cheryl jones of peloton advantage, llc, an open health company, and funded by bristol myers squibb disclosures • aa: grants and personal fees: abbvie, bristol myers squibb, eli lilly, janssen, leo pharma, and novartis; personal fees: boehringer ingelheim/parexel, celgene, dermavant, genentech, glaxosmithkline, menlo therapeutics, merck, modernizing medicine, ortho dermatologics, pfizer, regeneron, sanofi genzyme, science 37, sun pharma, and valeant; grants: dermira, kyowa hakko kirin, and ucb, outside the submitted work • rbw: research grants: abbvie, almirall, amgen, celgene, eli lilly, janssen, leo pharma, novartis, pfizer, and ucb; consulting fees: abbvie, almirall, amgen, biogen, boehringer ingelheim, celgene, dice, eli lilly, janssen, leo pharma, novartis, pfizer, sanofi, ucb, and union • yz, jz, rk, and cd: employees of and may own stock options in bristol myers squibb • ac, ak, dj, and tw: employed by evidera, a company that provides consulting and other research services to bristol myers squibb • ma: advisory boards: abbvie, amgen, boehringer ingelheim, janssen biotech, and leo pharma; consulting fees: abbvie, amgen, eli lilly, janssen biotech, leo pharma, novartis, sun pharma, and ucb; honoraria: abbvie, amgen, boehringer ingelheim, eli lilly, janssen biotech, leo pharma, novartis, sun pharma, and ucb; investigator: abbvie, amgen, boehringer ingelheim, celgene, eli lilly, janssen biotech, leo pharma, merck, novartis, sun pharma, and ucb; research grants: abbvie, amgen, boehringer ingelheim, celgene, janssen biotech, leo pharma, merck, and sun pharma; speaker: abbvie, amgen, janssen biotech, leo pharma, sun pharma, and ucb indirect comparison of the short-, mid-, and long-term efficacy of treatments for moderate to severe plaque psoriasis: a systematic review and network meta-analysis april armstrong,1 richard b. warren,2 yichen zhong,3 joe zhuo,3 allie cichewicz,4 ananth kadambi,4 daniela r. junqueira,4 tracy westley,4 renata kisa,3 carolin daamen,3 matthias augustin5 1university of southern california, los angeles, ca; 2the university of manchester, manchester, uk; 3bristol myers squibb, princeton, nj; 4evidera, bethesda, md; 5university medical center, hamburg, germany presented at the fall clinical dermatology conference; october 20–23, 2022; las vegas, nv this poster may not be reproduced without written permission from the authors.email for april armstrong, md, mph: aprilarmstrong@post.harvard.edu scientifi c content on demand to request a copy of this poster: scan qr code via a barcode reader application qr codes are valid for 30 days after congress presentation date synopsis • patients with moderate to severe plaque psoriasis have several systemic treatment choices available, including oral nonbiologic and biologic options • deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 (tyk2) inhibitor, demonstrated superior effi cacy versus apremilast and placebo in two phase 3 randomized controlled trials (rcts) and is approved by the us food and drug administration for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy • this systematic literature review (slr) and network meta-analysis (nma) indirectly compared the efficacy of deucravacitinib with that of other approved, relevant systemic biologic and nonbiologic treatments over short-, medium-, and long-term follow-up; multinomial random effects models estimated improvement in responses on the psoriasis area and severity index (pasi) at weeks 10−16, 24−28, and 44−60 • pasi 75 (75% improvement in pasi) response rate with deucravacitinib was comparable to that of first-generation biologics at week 16, and higher at week 24; at week 52, it was comparable to that of the most effective fi rstgeneration biologics objective • the objective of this analysis was to examine the clinical effi cacy associated with deucravacitinib and other selected active biologic and nonbiologic treatments in patients with moderate to severe psoriasis methods • electronic databases were searched through october 2021 for rcts of systemic treatments in adults with moderate to severe psoriasis who reported improvement in response on pasi • phase 3 trial data were included when: — nonresponder imputation was applied1,2 — studies were conducted in multiple or single countries with diverse ethnic representation • nma was performed using multinomial random effects models adjusting for baseline risk (ie, placebo response) to estimate pasi responses over short-, mid-, and long-term follow-up periods (weeks 10−16, 24−28, and 44−60, respectively) and reported following the prisma reporting guidelines for meta-analysis3 results • the slr identifi ed 47 phase 3 rcts that applied nonresponder imputation and were included in the nma (figure 1 and figure 2a); the mid-term analysis included 28 studies (figure 2b); the long-term analysis included 21 studies (figure 2c) figure 1. prisma flow diagram full-text articles excluded (n = 446) • duplicates (n = 11) • publication type not of interest (n = 17) • study design not of interest (n = 25) • population not of interest (n = 60) • intervention/comparator not of interest (n = 105) • outcomes not of interest (n = 189) • relevant slrs/nmas published 2019-2020 (n = 39) records excluded by title and abstract screening (n = 3632) full-text articles assessed for eligibility (n = 818) 251 rct publications and 132 pooleda analyses included in slr duplicates removed (n = 3037) rcts included in global pasi nma (n = 96 unique rcts)b records screened (n = 4450) rcts included in phase 3 global nri pasi nma (n = 47 unique rcts)b id e n ti fi ca ti o n sc re e n in g e li gi b il it y in cl u d e d records identified through database searching (n = 7487) records identified through other sources (conference proceedings: n = 11) apooled analyses of rcts were not included in the slr unless unique data were available that were not published elsewhere. brcts eligible for global pasi nma and phase 3 global nri pasi nma, including poetyk ps0-1 and poetyk pso-2. nma, network meta-analysis; nri, nonresponder imputation; pasi, psoriasis area and severity index; rct, randomized controlled trial; slr, systematic literature review. figure 2. network plots of trials included in the shortterm (10–16 weeks; a), mid-term (24–28 weeks; b), and long-term (44–60 weeks; c) analyses v etanercept study group liberate etanercept study group etanercept study group fixture m10-114 m10-315 opt compare study resurface 2 uncover 2, 3 liberate esteem 1, 2 liberate poetyk 1, 2poetyk 1, 2 fixture poetyk 1, 2 uncover 2, 3 uncover 1, 2, 3 erasure feature fixture juncture allure erasure feature fixture juncture amagine 2, 3 be vivid ultimma-1, -2 amagine 1, 2, 3 amagine 2, 3 clear immerge be vivid be radiant be ready be vivid orion voyage 1, 2 voyage 1, 2 be sure immvent voyage 1, 2 reveal champion express express ii spirit restore 1 resurface 1, 2 resurface 1, 2 phoenix 1, 2 resurface 1, 2 resurface 2 accept ust 90 mg til 200 mg til 100 mg ifx 5 mg/kg mtx 7.5 to 25 mg adm 40 mggus 100 mg bim 320 mg ust 45 or 90 mg sec 300 mg sec 150 mg apr 30 mg etc 25 mg biw etc 50 mg biw deuc 6 mg ixe 80 mg q2w bro 210 mg ris 150 mg pbo resurface 2 fixture reich, 2020 champion champion metop eclipse blauvelt, 2021 immhance ultimma-1, -2 ultimma-1, -2 ixora-5 erasure feature fixture juncture a. erasure feature fixture juncture erasure feature fixture juncture erasure feature fixture juncture amagine 2, 3 be vivid ultimma-1, -2 ultimma-1, -2 ultimma-1, -2 poetyk 1 uncover 3 amagine 2, 3 amagine 2, 3 immerge be radiant voyage 1 voyage 1 voyage 1 express express ii fixture fixturefixture metop eclipseixora-5 ifx 5 mg/kg mtx 7.5 to 25 mg adm 40 mggus 100 mg bim 320 mg ust 45 or 90 mg sec 300 mg sec 150 mg apr 30 mg etc 50 mg biw deuc 6 mg ixe 80 mg q2w bro 210 mg ris 150 mg pbo liberate clear c. etanercept study group etanercept study group esteem 1, 2 poetyk 1, 2poetyk 1, 2 fixture poetyk 1, 2 uncover 3 erasure feature fixture erasure feature fixture allure erasure feature fixture amagine 2, 3 be vivid amagine 1, 2, 3 amagine 2, 3 clear immhance immerge be radiant orion voyage 1, 2 voyage 1, 2 voyage 1, 2 be sure express express ii resurface 1, 2 resurface 1, 2 phoenix 1, 2 resurface 2 ust 90 mg til 200 mg til 100 mg ifx 5 mg/kg mtx 7.5 to 25 mg adm 40 mggus 100 mg bim 320 mg ust 45 or 90 mg sec 300 mg sec 150 mg apr 30 mg etc 25 mg biw etc 50 mg biw deuc 6 mg ixe 80 mg q2w bro 210 mg ris 150 mg pbo resurface 2 fixture metop eclipse ixora-5 resurface 1, 2 b. etanercept study group fixture resurface 2 act, acitretin; adm, adalimumab; apr, apremilast; bim, bimekizumab; biw, twice weekly; bro, brodalumab; deuc, deucravacitinib; etc, etanercept; gus, guselkumab; ifx, infl iximab; ixe, ixekizumab; mtx, methotrexate; pbo, placebo; ris, risankizumab; q2w, once every 2 weeks; sec, secukinumab; til, tildrakizumab; ust, ustekinumab. • pasi 75 response rate with deucravacitinib at week 16 (54.1%; credible interval [crl], 46.5%, 61.6%) was within range of the first-generation biologics (range, 39.7 [crl, 31.6%, 48.3%] for etanercept 25 mg to 79.0% [crl, 74.0%, 83.5%] for infl iximab; figure 3a) • pasi 75 response with deucravacitinib increased at week 24 to 63.3% (crl, 58.0%, 68.4%; figure 3b) • at week 52, the pasi 75 response rate for deucravacitinib (65.9%; crl, 58.0%, 73.4%) was comparable to that of the most effective first-generation biologics — adalimumab (62.8%; crl, 55.3%, 69.6%) and ustekinumab (68.0%; crl, 64.6%, 71.5%; figure 3c) • newer il-17 and il-23 inhibitors showed the highest pasi 75 response rates of the included treatments, across all time points figure 3. short-term estimated pasi 75 response,a posterior median and 95% cri. weeks 10–16 (a), midterm estimated pasi 75 response for weeks 24–28 (b), and long-term estimated pasi 75 response for weeks 44–60 (c) 56.7 ifx 5 mg/kg adm 40 mg 62.8 48.4 apr 30 mg 45.0 mtx ust 90 mg 70.9 ust 45 or 90 mg 71.1 5.8 33.5 40.1 54.1 39.7 49.8 71.7 79.0 84.8 85.7 89.0 93.0 63.0 64.2 87.8 89.6 0 10 20 30 40 50 60 70 80 90 100 pbo apr 30 mg mtx deuc 6 mg etc 25 mg biw/50 mg qw etc 50 mg biw adm 40 mg ifx 5 mg/kg sec 150 mg sec 300 mg bro 210 mg ixe 80 mg q2w bim 320b mg til 100 mg til 200 mg gus 100 mg ris 150 mg n m a e st im at e d p a si 7 5 re sp on se r at e , % nonbiologic oral anti-tnf anti–il-12/23 anti–il-17 anti–il-23 first-generation biologics second-generation biologics a. 71.3 6.4 54.0 77.0 81.0 83.9 86.4 87.8 91.6 0 10 20 30 40 50 60 70 80 90 100 pbo deuc 6 mg etc 50 mg biw ust 45 or 90 mg sec 150 mg sec 300 mg bro 210 mg ixe 80 mg q2w>q4w bim 320b mg q4w>q8w gus 100 mg ris 150 mg n m a e st im at e d p a si 7 5 re sp on se r at e , % nonbiologic oral anti-tnf anti–il–12/23 anti–il-17 anti–il-23 c. 62.1 68.0 65.9 6.4 34.8 50.1 63.3 43.7 54.4 84.7 86.2 89.6 92.1 89.5 93.8 0 10 20 30 40 50 60 70 80 90 100 pbo apr 30 mg mtx deuc 6 mg etc 25 mg biw/50 mg qw etc 50 mg biw adm 40 mg ifx 5 mg/kg ust 45 or 90 mg ust 90 mg sec 150 mg sec 300 mg bro 210 mg ixe 80 mg q2w>q4w bim 320b mg q4w>q8w til 100 mg til 200 mg gus 100 mg ris 150 mg n m a e st im at e d p a si 7 5 re sp on se r at e , % nonbiologic oral anti–tnf anti–il-12/23 anti–il-17 anti–il-23 b. 74.675.074.271.0 72.3 72.2 73.4 first-generation biologics second-generation biologics first-generation biologics second-generation biologics aadjusted for placebo response rates. bbim is not approved for use in the united states. note: posterior median value given for each therapy; error bars represent 95% cri. adm, adalimumab; apr, apremilast; bim, bimekizumab; biw, twice weekly; bro, brodalumab; cri, credible interval; deuc, deucravacitinib; etc, etanercept; gus, guselkumab; ifx, infl iximab; il, interleukin; ixe, ixekizumab; mtx, methotrexate; nma, network meta-analysis; pasi, psoriasis area and severity index; pbo, placebo; q2w, once every 2 weeks; q4w, once every 4 weeks; q8w, once every 8 weeks; ris, risankizumab; sec, secukinumab; til, tildrakizumab; tnf, tumor necrosis factor; ust, ustekinumab. conclusions • among oral nonbiologic treatments, deucravacitinib provided the best efficacy across time points compared with methotrexate and apremilast • the pasi 75 response rates for deucravacitinib were within the range of those for first-generation biologics at weeks 10–16 and 24–28 • at 1 year, the pasi 75 response rate for deucravacitinib was similar to that of adalimumab and ustekinumab • the psoriasis treatment paradigm is changing with the approval of deucravacitinib, a convenient oral therapy with a long-term effi cacy level similar to that of some biologic therapies references 1. guideline on missing data in confirmatory clinical trials. european medicines agency; 2010. https://www.ema.europa.eu/en/documents/ scientifi c-guideline/guideline-missing-data-confi rmatory-clinical-trials_ en.pdf 2. guidance for sponsors, clinical investigators, and irbs. us food and drug administration; 2008. http://www.fda.gov/downloads/ regulatoryinformation/guidances/ucm126489.pdf 3. page mj, et al. plos med. 2021;18:e1003583. acknowledgments • this study was sponsored by bristol myers squibb • medical writing and editorial assistance was provided by cheryl jones of peloton advantage, llc, an open health company, and funded by bristol myers squibb disclosures • aa: grants and personal fees: abbvie, bristol myers squibb, eli lilly, janssen, leo pharma, and novartis; personal fees: boehringer ingelheim/parexel, celgene, dermavant, genentech, glaxosmithkline, menlo therapeutics, merck, modernizing medicine, ortho dermatologics, pfizer, regeneron, sanofi genzyme, science 37, sun pharma, and valeant; grants: dermira, kyowa hakko kirin, and ucb, outside the submitted work • rbw: research grants: abbvie, almirall, amgen, celgene, eli lilly, janssen, leo pharma, novartis, pfizer, and ucb; consulting fees: abbvie, almirall, amgen, biogen, boehringer ingelheim, celgene, dice, eli lilly, janssen, leo pharma, novartis, pfizer, sanofi, ucb, and union • yz, jz, rk, and cd: employees of and may own stock options in bristol myers squibb • ac, ak, dj, and tw: employed by evidera, a company that provides consulting and other research services to bristol myers squibb • ma: advisory boards: abbvie, amgen, boehringer ingelheim, janssen biotech, and leo pharma; consulting fees: abbvie, amgen, eli lilly, janssen biotech, leo pharma, novartis, sun pharma, and ucb; honoraria: abbvie, amgen, boehringer ingelheim, eli lilly, janssen biotech, leo pharma, novartis, sun pharma, and ucb; investigator: abbvie, amgen, boehringer ingelheim, celgene, eli lilly, janssen biotech, leo pharma, merck, novartis, sun pharma, and ucb; research grants: abbvie, amgen, boehringer ingelheim, celgene, janssen biotech, leo pharma, merck, and sun pharma; speaker: abbvie, amgen, janssen biotech, leo pharma, sun pharma, and ucb indirect comparison of the short-, mid-, and long-term efficacy of treatments for moderate to severe plaque psoriasis: a systematic review and network meta-analysis april armstrong,1 richard b. warren,2 yichen zhong,3 joe zhuo,3 allie cichewicz,4 ananth kadambi,4 daniela r. junqueira,4 tracy westley,4 renata kisa,3 carolin daamen,3 matthias augustin5 1university of southern california, los angeles, ca; 2the university of manchester, manchester, uk; 3bristol myers squibb, princeton, nj; 4evidera, bethesda, md; 5university medical center, hamburg, germany presented at the fall clinical dermatology conference; october 20–23, 2022; las vegas, nv this poster may not be reproduced without written permission from the authors.email for april armstrong, md, mph: aprilarmstrong@post.harvard.edu scientifi c content on demand to request a copy of this poster: scan qr code via a barcode reader application qr codes are valid for 30 days after congress presentation date synopsis • patients with moderate to severe plaque psoriasis have several systemic treatment choices available, including oral nonbiologic and biologic options • deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 (tyk2) inhibitor, demonstrated superior effi cacy versus apremilast and placebo in two phase 3 randomized controlled trials (rcts) and is approved by the us food and drug administration for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy • this systematic literature review (slr) and network meta-analysis (nma) indirectly compared the efficacy of deucravacitinib with that of other approved, relevant systemic biologic and nonbiologic treatments over short-, medium-, and long-term follow-up; multinomial random effects models estimated improvement in responses on the psoriasis area and severity index (pasi) at weeks 10−16, 24−28, and 44−60 • pasi 75 (75% improvement in pasi) response rate with deucravacitinib was comparable to that of first-generation biologics at week 16, and higher at week 24; at week 52, it was comparable to that of the most effective fi rstgeneration biologics objective • the objective of this analysis was to examine the clinical effi cacy associated with deucravacitinib and other selected active biologic and nonbiologic treatments in patients with moderate to severe psoriasis methods • electronic databases were searched through october 2021 for rcts of systemic treatments in adults with moderate to severe psoriasis who reported improvement in response on pasi • phase 3 trial data were included when: — nonresponder imputation was applied1,2 — studies were conducted in multiple or single countries with diverse ethnic representation • nma was performed using multinomial random effects models adjusting for baseline risk (ie, placebo response) to estimate pasi responses over short-, mid-, and long-term follow-up periods (weeks 10−16, 24−28, and 44−60, respectively) and reported following the prisma reporting guidelines for meta-analysis3 results • the slr identifi ed 47 phase 3 rcts that applied nonresponder imputation and were included in the nma (figure 1 and figure 2a); the mid-term analysis included 28 studies (figure 2b); the long-term analysis included 21 studies (figure 2c) figure 1. prisma flow diagram full-text articles excluded (n = 446) • duplicates (n = 11) • publication type not of interest (n = 17) • study design not of interest (n = 25) • population not of interest (n = 60) • intervention/comparator not of interest (n = 105) • outcomes not of interest (n = 189) • relevant slrs/nmas published 2019-2020 (n = 39) records excluded by title and abstract screening (n = 3632) full-text articles assessed for eligibility (n = 818) 251 rct publications and 132 pooleda analyses included in slr duplicates removed (n = 3037) rcts included in global pasi nma (n = 96 unique rcts)b records screened (n = 4450) rcts included in phase 3 global nri pasi nma (n = 47 unique rcts)b id e n ti fi ca ti o n sc re e n in g e li gi b il it y in cl u d e d records identified through database searching (n = 7487) records identified through other sources (conference proceedings: n = 11) apooled analyses of rcts were not included in the slr unless unique data were available that were not published elsewhere. brcts eligible for global pasi nma and phase 3 global nri pasi nma, including poetyk ps0-1 and poetyk pso-2. nma, network meta-analysis; nri, nonresponder imputation; pasi, psoriasis area and severity index; rct, randomized controlled trial; slr, systematic literature review. figure 2. network plots of trials included in the shortterm (10–16 weeks; a), mid-term (24–28 weeks; b), and long-term (44–60 weeks; c) analyses v etanercept study group liberate etanercept study group etanercept study group fixture m10-114 m10-315 opt compare study resurface 2 uncover 2, 3 liberate esteem 1, 2 liberate poetyk 1, 2poetyk 1, 2 fixture poetyk 1, 2 uncover 2, 3 uncover 1, 2, 3 erasure feature fixture juncture allure erasure feature fixture juncture amagine 2, 3 be vivid ultimma-1, -2 amagine 1, 2, 3 amagine 2, 3 clear immerge be vivid be radiant be ready be vivid orion voyage 1, 2 voyage 1, 2 be sure immvent voyage 1, 2 reveal champion express express ii spirit restore 1 resurface 1, 2 resurface 1, 2 phoenix 1, 2 resurface 1, 2 resurface 2 accept ust 90 mg til 200 mg til 100 mg ifx 5 mg/kg mtx 7.5 to 25 mg adm 40 mggus 100 mg bim 320 mg ust 45 or 90 mg sec 300 mg sec 150 mg apr 30 mg etc 25 mg biw etc 50 mg biw deuc 6 mg ixe 80 mg q2w bro 210 mg ris 150 mg pbo resurface 2 fixture reich, 2020 champion champion metop eclipse blauvelt, 2021 immhance ultimma-1, -2 ultimma-1, -2 ixora-5 erasure feature fixture juncture a. erasure feature fixture juncture erasure feature fixture juncture erasure feature fixture juncture amagine 2, 3 be vivid ultimma-1, -2 ultimma-1, -2 ultimma-1, -2 poetyk 1 uncover 3 amagine 2, 3 amagine 2, 3 immerge be radiant voyage 1 voyage 1 voyage 1 express express ii fixture fixturefixture metop eclipseixora-5 ifx 5 mg/kg mtx 7.5 to 25 mg adm 40 mggus 100 mg bim 320 mg ust 45 or 90 mg sec 300 mg sec 150 mg apr 30 mg etc 50 mg biw deuc 6 mg ixe 80 mg q2w bro 210 mg ris 150 mg pbo liberate clear c. etanercept study group etanercept study group esteem 1, 2 poetyk 1, 2poetyk 1, 2 fixture poetyk 1, 2 uncover 3 erasure feature fixture erasure feature fixture allure erasure feature fixture amagine 2, 3 be vivid amagine 1, 2, 3 amagine 2, 3 clear immhance immerge be radiant orion voyage 1, 2 voyage 1, 2 voyage 1, 2 be sure express express ii resurface 1, 2 resurface 1, 2 phoenix 1, 2 resurface 2 ust 90 mg til 200 mg til 100 mg ifx 5 mg/kg mtx 7.5 to 25 mg adm 40 mggus 100 mg bim 320 mg ust 45 or 90 mg sec 300 mg sec 150 mg apr 30 mg etc 25 mg biw etc 50 mg biw deuc 6 mg ixe 80 mg q2w bro 210 mg ris 150 mg pbo resurface 2 fixture metop eclipse ixora-5 resurface 1, 2 b. etanercept study group fixture resurface 2 act, acitretin; adm, adalimumab; apr, apremilast; bim, bimekizumab; biw, twice weekly; bro, brodalumab; deuc, deucravacitinib; etc, etanercept; gus, guselkumab; ifx, infl iximab; ixe, ixekizumab; mtx, methotrexate; pbo, placebo; ris, risankizumab; q2w, once every 2 weeks; sec, secukinumab; til, tildrakizumab; ust, ustekinumab. • pasi 75 response rate with deucravacitinib at week 16 (54.1%; credible interval [crl], 46.5%, 61.6%) was within range of the first-generation biologics (range, 39.7 [crl, 31.6%, 48.3%] for etanercept 25 mg to 79.0% [crl, 74.0%, 83.5%] for infl iximab; figure 3a) • pasi 75 response with deucravacitinib increased at week 24 to 63.3% (crl, 58.0%, 68.4%; figure 3b) • at week 52, the pasi 75 response rate for deucravacitinib (65.9%; crl, 58.0%, 73.4%) was comparable to that of the most effective first-generation biologics — adalimumab (62.8%; crl, 55.3%, 69.6%) and ustekinumab (68.0%; crl, 64.6%, 71.5%; figure 3c) • newer il-17 and il-23 inhibitors showed the highest pasi 75 response rates of the included treatments, across all time points figure 3. short-term estimated pasi 75 response,a posterior median and 95% cri. weeks 10–16 (a), midterm estimated pasi 75 response for weeks 24–28 (b), and long-term estimated pasi 75 response for weeks 44–60 (c) 56.7 ifx 5 mg/kg adm 40 mg 62.8 48.4 apr 30 mg 45.0 mtx ust 90 mg 70.9 ust 45 or 90 mg 71.1 5.8 33.5 40.1 54.1 39.7 49.8 71.7 79.0 84.8 85.7 89.0 93.0 63.0 64.2 87.8 89.6 0 10 20 30 40 50 60 70 80 90 100 pbo apr 30 mg mtx deuc 6 mg etc 25 mg biw/50 mg qw etc 50 mg biw adm 40 mg ifx 5 mg/kg sec 150 mg sec 300 mg bro 210 mg ixe 80 mg q2w bim 320b mg til 100 mg til 200 mg gus 100 mg ris 150 mg n m a e st im at e d p a si 7 5 re sp on se r at e , % nonbiologic oral anti-tnf anti–il-12/23 anti–il-17 anti–il-23 first-generation biologics second-generation biologics a. 71.3 6.4 54.0 77.0 81.0 83.9 86.4 87.8 91.6 0 10 20 30 40 50 60 70 80 90 100 pbo deuc 6 mg etc 50 mg biw ust 45 or 90 mg sec 150 mg sec 300 mg bro 210 mg ixe 80 mg q2w>q4w bim 320b mg q4w>q8w gus 100 mg ris 150 mg n m a e st im at e d p a si 7 5 re sp on se r at e , % nonbiologic oral anti-tnf anti–il–12/23 anti–il-17 anti–il-23 c. 62.1 68.0 65.9 6.4 34.8 50.1 63.3 43.7 54.4 84.7 86.2 89.6 92.1 89.5 93.8 0 10 20 30 40 50 60 70 80 90 100 pbo apr 30 mg mtx deuc 6 mg etc 25 mg biw/50 mg qw etc 50 mg biw adm 40 mg ifx 5 mg/kg ust 45 or 90 mg ust 90 mg sec 150 mg sec 300 mg bro 210 mg ixe 80 mg q2w>q4w bim 320b mg q4w>q8w til 100 mg til 200 mg gus 100 mg ris 150 mg n m a e st im at e d p a si 7 5 re sp on se r at e , % nonbiologic oral anti–tnf anti–il-12/23 anti–il-17 anti–il-23 b. 74.675.074.271.0 72.3 72.2 73.4 first-generation biologics second-generation biologics first-generation biologics second-generation biologics aadjusted for placebo response rates. bbim is not approved for use in the united states. note: posterior median value given for each therapy; error bars represent 95% cri. adm, adalimumab; apr, apremilast; bim, bimekizumab; biw, twice weekly; bro, brodalumab; cri, credible interval; deuc, deucravacitinib; etc, etanercept; gus, guselkumab; ifx, infl iximab; il, interleukin; ixe, ixekizumab; mtx, methotrexate; nma, network meta-analysis; pasi, psoriasis area and severity index; pbo, placebo; q2w, once every 2 weeks; q4w, once every 4 weeks; q8w, once every 8 weeks; ris, risankizumab; sec, secukinumab; til, tildrakizumab; tnf, tumor necrosis factor; ust, ustekinumab. conclusions • among oral nonbiologic treatments, deucravacitinib provided the best efficacy across time points compared with methotrexate and apremilast • the pasi 75 response rates for deucravacitinib were within the range of those for first-generation biologics at weeks 10–16 and 24–28 • at 1 year, the pasi 75 response rate for deucravacitinib was similar to that of adalimumab and ustekinumab • the psoriasis treatment paradigm is changing with the approval of deucravacitinib, a convenient oral therapy with a long-term effi cacy level similar to that of some biologic therapies references 1. guideline on missing data in confirmatory clinical trials. european medicines agency; 2010. https://www.ema.europa.eu/en/documents/ scientifi c-guideline/guideline-missing-data-confi rmatory-clinical-trials_ en.pdf 2. guidance for sponsors, clinical investigators, and irbs. us food and drug administration; 2008. http://www.fda.gov/downloads/ regulatoryinformation/guidances/ucm126489.pdf 3. page mj, et al. plos med. 2021;18:e1003583. acknowledgments • this study was sponsored by bristol myers squibb • medical writing and editorial assistance was provided by cheryl jones of peloton advantage, llc, an open health company, and funded by bristol myers squibb disclosures • aa: grants and personal fees: abbvie, bristol myers squibb, eli lilly, janssen, leo pharma, and novartis; personal fees: boehringer ingelheim/parexel, celgene, dermavant, genentech, glaxosmithkline, menlo therapeutics, merck, modernizing medicine, ortho dermatologics, pfizer, regeneron, sanofi genzyme, science 37, sun pharma, and valeant; grants: dermira, kyowa hakko kirin, and ucb, outside the submitted work • rbw: research grants: abbvie, almirall, amgen, celgene, eli lilly, janssen, leo pharma, novartis, pfizer, and ucb; consulting fees: abbvie, almirall, amgen, biogen, boehringer ingelheim, celgene, dice, eli lilly, janssen, leo pharma, novartis, pfizer, sanofi, ucb, and union • yz, jz, rk, and cd: employees of and may own stock options in bristol myers squibb • ac, ak, dj, and tw: employed by evidera, a company that provides consulting and other research services to bristol myers squibb • ma: advisory boards: abbvie, amgen, boehringer ingelheim, janssen biotech, and leo pharma; consulting fees: abbvie, amgen, eli lilly, janssen biotech, leo pharma, novartis, sun pharma, and ucb; honoraria: abbvie, amgen, boehringer ingelheim, eli lilly, janssen biotech, leo pharma, novartis, sun pharma, and ucb; investigator: abbvie, amgen, boehringer ingelheim, celgene, eli lilly, janssen biotech, leo pharma, merck, novartis, sun pharma, and ucb; research grants: abbvie, amgen, boehringer ingelheim, celgene, janssen biotech, leo pharma, merck, and sun pharma; speaker: abbvie, amgen, janssen biotech, leo pharma, sun pharma, and ucb indirect comparison of the short-, mid-, and long-term efficacy of treatments for moderate to severe plaque psoriasis: a systematic review and network meta-analysis april armstrong,1 richard b. warren,2 yichen zhong,3 joe zhuo,3 allie cichewicz,4 ananth kadambi,4 daniela r. junqueira,4 tracy westley,4 renata kisa,3 carolin daamen,3 matthias augustin5 1university of southern california, los angeles, ca; 2the university of manchester, manchester, uk; 3bristol myers squibb, princeton, nj; 4evidera, bethesda, md; 5university medical center, hamburg, germany presented at the fall clinical dermatology conference; october 20–23, 2022; las vegas, nv this poster may not be reproduced without written permission from the authors.email for april armstrong, md, mph: aprilarmstrong@post.harvard.edu scientifi c content on demand to request a copy of this poster: scan qr code via a barcode reader application qr codes are valid for 30 days after congress presentation date synopsis • patients with moderate to severe plaque psoriasis have several systemic treatment choices available, including oral nonbiologic and biologic options • deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 (tyk2) inhibitor, demonstrated superior effi cacy versus apremilast and placebo in two phase 3 randomized controlled trials (rcts) and is approved by the us food and drug administration for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy • this systematic literature review (slr) and network meta-analysis (nma) indirectly compared the efficacy of deucravacitinib with that of other approved, relevant systemic biologic and nonbiologic treatments over short-, medium-, and long-term follow-up; multinomial random effects models estimated improvement in responses on the psoriasis area and severity index (pasi) at weeks 10−16, 24−28, and 44−60 • pasi 75 (75% improvement in pasi) response rate with deucravacitinib was comparable to that of first-generation biologics at week 16, and higher at week 24; at week 52, it was comparable to that of the most effective fi rstgeneration biologics objective • the objective of this analysis was to examine the clinical effi cacy associated with deucravacitinib and other selected active biologic and nonbiologic treatments in patients with moderate to severe psoriasis methods • electronic databases were searched through october 2021 for rcts of systemic treatments in adults with moderate to severe psoriasis who reported improvement in response on pasi • phase 3 trial data were included when: — nonresponder imputation was applied1,2 — studies were conducted in multiple or single countries with diverse ethnic representation • nma was performed using multinomial random effects models adjusting for baseline risk (ie, placebo response) to estimate pasi responses over short-, mid-, and long-term follow-up periods (weeks 10−16, 24−28, and 44−60, respectively) and reported following the prisma reporting guidelines for meta-analysis3 results • the slr identifi ed 47 phase 3 rcts that applied nonresponder imputation and were included in the nma (figure 1 and figure 2a); the mid-term analysis included 28 studies (figure 2b); the long-term analysis included 21 studies (figure 2c) figure 1. prisma flow diagram full-text articles excluded (n = 446) • duplicates (n = 11) • publication type not of interest (n = 17) • study design not of interest (n = 25) • population not of interest (n = 60) • intervention/comparator not of interest (n = 105) • outcomes not of interest (n = 189) • relevant slrs/nmas published 2019-2020 (n = 39) records excluded by title and abstract screening (n = 3632) full-text articles assessed for eligibility (n = 818) 251 rct publications and 132 pooleda analyses included in slr duplicates removed (n = 3037) rcts included in global pasi nma (n = 96 unique rcts)b records screened (n = 4450) rcts included in phase 3 global nri pasi nma (n = 47 unique rcts)b id e n ti fi ca ti o n sc re e n in g e li gi b il it y in cl u d e d records identified through database searching (n = 7487) records identified through other sources (conference proceedings: n = 11) apooled analyses of rcts were not included in the slr unless unique data were available that were not published elsewhere. brcts eligible for global pasi nma and phase 3 global nri pasi nma, including poetyk ps0-1 and poetyk pso-2. nma, network meta-analysis; nri, nonresponder imputation; pasi, psoriasis area and severity index; rct, randomized controlled trial; slr, systematic literature review. figure 2. network plots of trials included in the shortterm (10–16 weeks; a), mid-term (24–28 weeks; b), and long-term (44–60 weeks; c) analyses v etanercept study group liberate etanercept study group etanercept study group fixture m10-114 m10-315 opt compare study resurface 2 uncover 2, 3 liberate esteem 1, 2 liberate poetyk 1, 2poetyk 1, 2 fixture poetyk 1, 2 uncover 2, 3 uncover 1, 2, 3 erasure feature fixture juncture allure erasure feature fixture juncture amagine 2, 3 be vivid ultimma-1, -2 amagine 1, 2, 3 amagine 2, 3 clear immerge be vivid be radiant be ready be vivid orion voyage 1, 2 voyage 1, 2 be sure immvent voyage 1, 2 reveal champion express express ii spirit restore 1 resurface 1, 2 resurface 1, 2 phoenix 1, 2 resurface 1, 2 resurface 2 accept ust 90 mg til 200 mg til 100 mg ifx 5 mg/kg mtx 7.5 to 25 mg adm 40 mggus 100 mg bim 320 mg ust 45 or 90 mg sec 300 mg sec 150 mg apr 30 mg etc 25 mg biw etc 50 mg biw deuc 6 mg ixe 80 mg q2w bro 210 mg ris 150 mg pbo resurface 2 fixture reich, 2020 champion champion metop eclipse blauvelt, 2021 immhance ultimma-1, -2 ultimma-1, -2 ixora-5 erasure feature fixture juncture a. erasure feature fixture juncture erasure feature fixture juncture erasure feature fixture juncture amagine 2, 3 be vivid ultimma-1, -2 ultimma-1, -2 ultimma-1, -2 poetyk 1 uncover 3 amagine 2, 3 amagine 2, 3 immerge be radiant voyage 1 voyage 1 voyage 1 express express ii fixture fixturefixture metop eclipseixora-5 ifx 5 mg/kg mtx 7.5 to 25 mg adm 40 mggus 100 mg bim 320 mg ust 45 or 90 mg sec 300 mg sec 150 mg apr 30 mg etc 50 mg biw deuc 6 mg ixe 80 mg q2w bro 210 mg ris 150 mg pbo liberate clear c. etanercept study group etanercept study group esteem 1, 2 poetyk 1, 2poetyk 1, 2 fixture poetyk 1, 2 uncover 3 erasure feature fixture erasure feature fixture allure erasure feature fixture amagine 2, 3 be vivid amagine 1, 2, 3 amagine 2, 3 clear immhance immerge be radiant orion voyage 1, 2 voyage 1, 2 voyage 1, 2 be sure express express ii resurface 1, 2 resurface 1, 2 phoenix 1, 2 resurface 2 ust 90 mg til 200 mg til 100 mg ifx 5 mg/kg mtx 7.5 to 25 mg adm 40 mggus 100 mg bim 320 mg ust 45 or 90 mg sec 300 mg sec 150 mg apr 30 mg etc 25 mg biw etc 50 mg biw deuc 6 mg ixe 80 mg q2w bro 210 mg ris 150 mg pbo resurface 2 fixture metop eclipse ixora-5 resurface 1, 2 b. etanercept study group fixture resurface 2 act, acitretin; adm, adalimumab; apr, apremilast; bim, bimekizumab; biw, twice weekly; bro, brodalumab; deuc, deucravacitinib; etc, etanercept; gus, guselkumab; ifx, infl iximab; ixe, ixekizumab; mtx, methotrexate; pbo, placebo; ris, risankizumab; q2w, once every 2 weeks; sec, secukinumab; til, tildrakizumab; ust, ustekinumab. • pasi 75 response rate with deucravacitinib at week 16 (54.1%; credible interval [crl], 46.5%, 61.6%) was within range of the first-generation biologics (range, 39.7 [crl, 31.6%, 48.3%] for etanercept 25 mg to 79.0% [crl, 74.0%, 83.5%] for infl iximab; figure 3a) • pasi 75 response with deucravacitinib increased at week 24 to 63.3% (crl, 58.0%, 68.4%; figure 3b) • at week 52, the pasi 75 response rate for deucravacitinib (65.9%; crl, 58.0%, 73.4%) was comparable to that of the most effective first-generation biologics — adalimumab (62.8%; crl, 55.3%, 69.6%) and ustekinumab (68.0%; crl, 64.6%, 71.5%; figure 3c) • newer il-17 and il-23 inhibitors showed the highest pasi 75 response rates of the included treatments, across all time points figure 3. short-term estimated pasi 75 response,a posterior median and 95% cri. weeks 10–16 (a), midterm estimated pasi 75 response for weeks 24–28 (b), and long-term estimated pasi 75 response for weeks 44–60 (c) 56.7 ifx 5 mg/kg adm 40 mg 62.8 48.4 apr 30 mg 45.0 mtx ust 90 mg 70.9 ust 45 or 90 mg 71.1 5.8 33.5 40.1 54.1 39.7 49.8 71.7 79.0 84.8 85.7 89.0 93.0 63.0 64.2 87.8 89.6 0 10 20 30 40 50 60 70 80 90 100 pbo apr 30 mg mtx deuc 6 mg etc 25 mg biw/50 mg qw etc 50 mg biw adm 40 mg ifx 5 mg/kg sec 150 mg sec 300 mg bro 210 mg ixe 80 mg q2w bim 320b mg til 100 mg til 200 mg gus 100 mg ris 150 mg n m a e st im at e d p a si 7 5 re sp on se r at e , % nonbiologic oral anti-tnf anti–il-12/23 anti–il-17 anti–il-23 first-generation biologics second-generation biologics a. 71.3 6.4 54.0 77.0 81.0 83.9 86.4 87.8 91.6 0 10 20 30 40 50 60 70 80 90 100 pbo deuc 6 mg etc 50 mg biw ust 45 or 90 mg sec 150 mg sec 300 mg bro 210 mg ixe 80 mg q2w>q4w bim 320b mg q4w>q8w gus 100 mg ris 150 mg n m a e st im at e d p a si 7 5 re sp on se r at e , % nonbiologic oral anti-tnf anti–il–12/23 anti–il-17 anti–il-23 c. 62.1 68.0 65.9 6.4 34.8 50.1 63.3 43.7 54.4 84.7 86.2 89.6 92.1 89.5 93.8 0 10 20 30 40 50 60 70 80 90 100 pbo apr 30 mg mtx deuc 6 mg etc 25 mg biw/50 mg qw etc 50 mg biw adm 40 mg ifx 5 mg/kg ust 45 or 90 mg ust 90 mg sec 150 mg sec 300 mg bro 210 mg ixe 80 mg q2w>q4w bim 320b mg q4w>q8w til 100 mg til 200 mg gus 100 mg ris 150 mg n m a e st im at e d p a si 7 5 re sp on se r at e , % nonbiologic oral anti–tnf anti–il-12/23 anti–il-17 anti–il-23 b. 74.675.074.271.0 72.3 72.2 73.4 first-generation biologics second-generation biologics first-generation biologics second-generation biologics aadjusted for placebo response rates. bbim is not approved for use in the united states. note: posterior median value given for each therapy; error bars represent 95% cri. adm, adalimumab; apr, apremilast; bim, bimekizumab; biw, twice weekly; bro, brodalumab; cri, credible interval; deuc, deucravacitinib; etc, etanercept; gus, guselkumab; ifx, infl iximab; il, interleukin; ixe, ixekizumab; mtx, methotrexate; nma, network meta-analysis; pasi, psoriasis area and severity index; pbo, placebo; q2w, once every 2 weeks; q4w, once every 4 weeks; q8w, once every 8 weeks; ris, risankizumab; sec, secukinumab; til, tildrakizumab; tnf, tumor necrosis factor; ust, ustekinumab. conclusions • among oral nonbiologic treatments, deucravacitinib provided the best efficacy across time points compared with methotrexate and apremilast • the pasi 75 response rates for deucravacitinib were within the range of those for first-generation biologics at weeks 10–16 and 24–28 • at 1 year, the pasi 75 response rate for deucravacitinib was similar to that of adalimumab and ustekinumab • the psoriasis treatment paradigm is changing with the approval of deucravacitinib, a convenient oral therapy with a long-term effi cacy level similar to that of some biologic therapies references 1. guideline on missing data in confirmatory clinical trials. european medicines agency; 2010. https://www.ema.europa.eu/en/documents/ scientifi c-guideline/guideline-missing-data-confi rmatory-clinical-trials_ en.pdf 2. guidance for sponsors, clinical investigators, and irbs. us food and drug administration; 2008. http://www.fda.gov/downloads/ regulatoryinformation/guidances/ucm126489.pdf 3. page mj, et al. plos med. 2021;18:e1003583. acknowledgments • this study was sponsored by bristol myers squibb • medical writing and editorial assistance was provided by cheryl jones of peloton advantage, llc, an open health company, and funded by bristol myers squibb disclosures • aa: grants and personal fees: abbvie, bristol myers squibb, eli lilly, janssen, leo pharma, and novartis; personal fees: boehringer ingelheim/parexel, celgene, dermavant, genentech, glaxosmithkline, menlo therapeutics, merck, modernizing medicine, ortho dermatologics, pfizer, regeneron, sanofi genzyme, science 37, sun pharma, and valeant; grants: dermira, kyowa hakko kirin, and ucb, outside the submitted work • rbw: research grants: abbvie, almirall, amgen, celgene, eli lilly, janssen, leo pharma, novartis, pfizer, and ucb; consulting fees: abbvie, almirall, amgen, biogen, boehringer ingelheim, celgene, dice, eli lilly, janssen, leo pharma, novartis, pfizer, sanofi, ucb, and union • yz, jz, rk, and cd: employees of and may own stock options in bristol myers squibb • ac, ak, dj, and tw: employed by evidera, a company that provides consulting and other research services to bristol myers squibb • ma: advisory boards: abbvie, amgen, boehringer ingelheim, janssen biotech, and leo pharma; consulting fees: abbvie, amgen, eli lilly, janssen biotech, leo pharma, novartis, sun pharma, and ucb; honoraria: abbvie, amgen, boehringer ingelheim, eli lilly, janssen biotech, leo pharma, novartis, sun pharma, and ucb; investigator: abbvie, amgen, boehringer ingelheim, celgene, eli lilly, janssen biotech, leo pharma, merck, novartis, sun pharma, and ucb; research grants: abbvie, amgen, boehringer ingelheim, celgene, janssen biotech, leo pharma, merck, and sun pharma; speaker: abbvie, amgen, janssen biotech, leo pharma, sun pharma, and ucb skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 556 clinical management recommendations incorporating prognostic gene expression profile assays into the management of cutaneous melanoma: an expert consensus panel report danny zakria, md, mba1, nicholas brownstone, md2, brian berman, md3, roger ceilley, md4, gary goldenberg, md1, mark lebwohl, md1, graham litchman, do5, daniel siegel, md6 1department of dermatology, icahn school of medicine at mount sinai, new york, ny 2department of dermatology, temple university health, philadelphia, pa 3department of dermatology & cutaneous surgery, university of miami miller school of medicine, miami, fl 4department of dermatology, the university of iowa, iowa city, ia 5department of dermatology, st. john’s episcopal hospital, far rockaway, ny 6department of dermatology, suny downstate, brooklyn, ny abstract background: cutaneous melanoma (cm) guidelines put forth by the eighth edition of the american joint committee on cancer (ajcc8) and the national comprehensive cancer network (nccn) do not currently account for lesion genomics when assessing prognosis. gene expression profile (gep) tests have become a widely adopted tool to help clinicians identify patients at higher risk for metastasis and recurrence. objective: to review the available literature that has been published since a consensus panel in 2018 on three commercially available gep tests used in the prognostic assessment of cm and create updated guidelines and consensus statements for their optimal use. methods: a comprehensive literature search of pubmed and google scholar was conducted for relevant english-language original research articles, meta-analyses, and systematic reviews published from 2019 through 2022. a panel of 6 key opinion leaders in dermatology with specialized expertise in diagnosing and managing cm then convened to review the articles and create guidelines. a modified delphi process was used to approve each statement. the panel assigned each article a level of evidence and each consensus statement a strength of recommendation using strength of recommendation taxonomy (sort) criteria. results: the literature search identified 785 articles that met the search criteria. of these, there were 22 articles that validated the 31-gep test, 2 that validated the 11-gep test, and 7 that validated the 8-gep + cp test. the panel unanimously approved 6 usage guidelines and 5 consensus supporting statements for the appropriate use of these tests. conclusion: based on the currently available literature, gep tests provide valuable information beyond ajcc8 and nccn guidelines for the prognostic assessment of cm. there are significantly more validation studies supporting the use of the 31-gep test compared to the 11-gep test and the 8-gep + cp test. skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 557 the incidence of cutaneous melanoma (cm) is increasing faster than any other malignancy.1 early detection is paramount, as prognosis is significantly impacted by stage at diagnosis. with traditional prognostic assessment using the eighth edition of the american joint committee on cancer (ajcc8), stage i cm has a 10-year overall survival (os) of 94 to 98% while stage iv disease has a 10-year os of 10 to 15%.2 the development and validation of gene expression profile (gep) assays that use a quantitative reverse-transcriptase polymerase chain reaction (qrt-pcr) to identify the level of expression of certain groups of signature genes has significantly advanced cancer prognostic assessment.3-8 because the level of expression of these signature genes varies between benign and malignant lesions as well as lesions that have a lower or higher likelihood for metastasis, these tests can provide important prognostic information. in addition, studies have demonstrated that genomics can identify a high-risk subset of cm patients with stage i and ii disease that are at greater risk for recurrence, metastasis, and increased mortality based on their lesions’ genetic profile.3-5 tens of thousands of cm gep tests are currently being ordered annually in the us to aid clinicians in their prognostic assessment of patients with cm.9 however, current cm staging according to ajcc8 as well as guidelines put forth by the national comprehensive cancer network (nccn) do not formally incorporate gep test data to further stratify patients. berman et. al reviewed the literature available through 2018 to provide clinical management recommendations on the use of gep tests for cm diagnosis and prognosis.10 the purpose of this current expert consensus panel was to review the multiple studies published subsequent to that paper on the validity, accuracy, and utility of commercially available cm gep prognostic tests to provide updated guidance on their usage. selection of gep assays it was specified prior to the review that the recommendations would be based on prognostic gep assays for cm that have published studies evaluating validity and efficacy, are commercially available, and used regularly. this resulted in the selection of 3 gep tests that met inclusion criteria: the 31-gep test (decisiondxtm-melanoma, castle biosciences, inc.), the 11-gep test (melagenix, neracare gmbh), and the 8gep + cp test (merlin, skylinedx, b.v.). 31-gep test the 31-gep test is a cm prognostic assay that measures the level of expression of 28 target genes and three control genes in order to stratify cm into low-risk (class 1a), intermediate risk (class 1b/2a), and high-risk (class 2b) categories based on risk of recurrence, metastasis and probability of sentinel lymph node biopsy (slnb) positivity.3 the test utilizes rna from formalin-fixed, paraffin-embedded (ffpe) tissue samples of the primary lesion and identifies the level of expression of the 31 genes using qrt-pcr.3 the test also adds clinical and histologic data into the gep values to provide an integrated prognostic assessment (i31-gep test). 11-gep test introduction methods skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 558 the 11-gep test is a cm prognostic test that measures the level of expression of eight target genes and three control genes.11 this test also measures gene expression from ffpe tissue samples after total rna from the samples is reverse transcribed.12 the test uses a continuous scoring system with 0 as the cut-off, such that a score ≤ 0 is considered “low-risk” for recurrence and a score > 0 is considered “high-risk” for recurrence.12 8-gep + cp test the 8-gep + cp test was derived from a logistic regression model consisting of eight genes and two clinicopathologic factors analyzed to predict sentinel node positivity.13 these genes are primarily involved in epithelial-to-mesenchymal transition, angiogenesis/hypoxia, and coagulation.13 this test dichotomizes patients into two groups: “low-risk” and “high-risk” for metastasis and relapse. literature search a comprehensive literature search of medline and google scholar was completed on november 3, 2022, using the keywords “cutaneous melanoma,” gene expression profile”, “genomics,” and “prognosis” along with the boolean term “and” for english-language original research articles, meta-analyses, and systematic reviews published from 2019 through 2022. articles were screened for relevance based on the description of studies that use gep tests to assess prognosis in cm. the selected articles were then appraised by the panel and assigned a level of evidence of “level 1,” “level 2,” or “level 3” using the strength of recommendation taxonomy (sort) criteria.14 development of consensus statements a panel of six dermatologists with specialized expertise in managing cm met on december 1, 2022, to review the selected articles. based upon their review and evaluation of the papers, formal recommendations to guide clinicians on the use of gep tests were developed. a modified delphi process was used to achieve consensus among the panelists.14 this technique employed multiple rounds of real-time voting and a required supermajority approval to adopt a recommendation. if a recommendation did not achieve supermajority acceptance, further modification through group discussion and subsequent rounds of voting occurred. the modified delphi process has been utilized frequently to create expert recommendations within dermatology.10, 16-18 comprehensive literature search the initial literature search resulted in 785 articles that met the search criteria. after screening the articles, 32 met inclusion criteria and were distributed to the panelists for review prior to the roundtable discussion. of these articles, the number of papers that specifically studied the validity, accuracy, or clinical utility of each test was: 22 for the 31gep test4,19-24,26-31,34-42, 2 for the 11-gep test11,34, and 7 for the 8-gep + cp test.5,13,23,43-46 levels of evidence designation the panelists assigned each of the included studies a level of evidence based on sort criteria (tables 1-3).14 of the 22 articles that specifically analyzed data from the 31-gep test, 8 were deemed to represent level 1 evidence, 12 were deemed to represent level results skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 559 table 1. strength of recommendation taxonomy (sort) level of evidence for articles pertaining to the 31-gep test. article level of evidence articles reporting data on validity, accuracy, or clinical utility ahmed k, siegel jj, morgan-linnell sk, et al. attitudes of patients with cutaneous melanoma toward prognostic testing using the 31-gene expression profile test [published online ahead of print, 2022 aug 1]. cancer med. 2022;10.1002/cam4.5047. 3 arnot sp, han g, fortino j, et al. utility of a 31-gene expression profile for predicting outcomes in patients with primary cutaneous melanoma referred for sentinel node biopsy. am j surg. 2021;221(6):1195-1199. 1 dillon ld, mcphee m, davidson rs, et al. expanded evidence that the 31-gene expression profile test provides clinical utility for melanoma management in a multicenter study. curr med res opin. 2022;38(8):1267-1274. 2 gastman br, zager js, messina jl, et al. performance of a 31-gene expression profile test in cutaneous melanomas of the head and neck. head neck. 2019;41(4):871-879. 2 glazer a, tassavor m, portela d, et al. (2022). the integrated 31-gene expression profile test (i31-gep) for cutaneous melanoma outperforms the cp-gep at identifying patients who can forego sentinel lymph node biopsy when applying nccn guidelines. skin the journal of cutaneous medicine, 6(6), 474–481. 2 greenhaw bn, covington kr, kurley sj, et al. molecular risk prediction in cutaneous melanoma: a metaanalysis of the 31-gene expression profile prognostic test in 1,479 patients. j am acad dermatol. 2020;83(3):745-753. 1 hsueh ec, debloom jr, lee jh, et al. long-term outcomes in a multicenter, prospective cohort evaluating the prognostic 31-gene expression profile for cutaneous melanoma. jco precis oncol. 2021;5:po.20.00119. 1 hyams dm, covington kr, johnson ce, plasseraud km, cook rw. integrating the melanoma 31-gene expression profile test with surgical oncology practice within national guideline and staging recommendations. future oncol. 2021;17(5):517-527. 2 jarell a, skenderis b, dillon ld, et al. the 31-gene expression profile stratifies recurrence and metastasis risk in patients with cutaneous melanoma. future oncol. 2021;17(36):5023-5031. 2 jarell a, gastman br, dillon ld, et al. optimizing treatment approaches for patients with cutaneous melanoma by integrating clinical and pathologic features with the 31-gene expression profile test. j am acad dermatol. 2022;87(6):1312-1320. 2 kangas-dick aw, greenbaum a, gall v, et al. evaluation of a gene expression profiling assay in primary cutaneous melanoma. ann surg oncol. 2021;28(8):4582-4589. 2 keller j, schwartz tl, lizalek jm, et al. prospective validation of the prognostic 31-gene expression profiling test in primary cutaneous melanoma. cancer med. 2019;8(5):2205-2212. 1 marchetti ma, coit dg, dusza sw, et al. performance of gene expression profile tests for prognosis in patients with localized cutaneous melanoma: a systematic review and meta-analysis. jama dermatol. 2020;156(9):953-962. 1 skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 560 marchetti ma, dusza sw, bartlett ek. utility of a model for predicting the risk of sentinel lymph node metastasis in patients with cutaneous melanoma. jama dermatol. 2022;158(6):680-683. 2 martin bj, covington kr, quick ap, cook rw. risk stratification of patients with stage i cutaneous melanoma using 31-gene expression profiling. j clin aesthet dermatol. 2021;14(9):e61-e63. 3 podlipnik s, boada a, lópez-estebaranz jl, et al. using a 31-gene expression profile test to stratify patients with stage i-ii cutaneous melanoma according to recurrence risk: update to a prospective, multicenter study. cancers (basel). 2022;14(4):1060. 1 podlipnik s, carrera c, boada a, et al. early outcome of a 31-gene expression profile test in 86 ajcc stage ib-ii melanoma patients. a prospective multicentre cohort study. j eur acad dermatol venereol. 2019;33(5):857-862. 1 thorpe rb, covington kr, caruso hg, et al. development and validation of a nomogram incorporating gene expression profiling and clinical factors for accurate prediction of metastasis in patients with cutaneous melanoma following mohs micrographic surgery. j am acad dermatol. 2022;86(4):846-853. 2 vetto jt, hsueh ec, gastman br, et al. guidance of sentinel lymph node biopsy decisions in patients with t1-t2 melanoma using gene expression profiling. future oncol. 2019;15(11):1207-1217. 1 whitman ed, koshenkov vp, gastman br, et al. integrating 31-gene expression profiling with clinicopathologic features to optimize cutaneous melanoma sentinel lymph node metastasis prediction. jco precis oncol. 2021;5:po.21.00162. published 2021 sep 13. 2 wisco oj, marson jw, litchman gh, et al. improved cutaneous melanoma survival stratification through integration of 31-gene expression profile testing with the american joint committee on cancer 8th edition staging. melanoma res. 2022;32(2):98-102. 2 zakria, d., brownstone, n., & rigel, d. (2022). the integrated 31-gene expression profile (i31-gep) test for cutaneous melanoma outperforms a clinicopathologic-only nomogram at identifying patients who can forego sentinel lymph node biopsy. skin the journal of cutaneous medicine, 6(6), 463–473. 2 systematic reviews or consensus guidelines grossman d, okwundu n, bartlett ek, et al. prognostic gene expression profiling in cutaneous melanoma: identifying the knowledge gaps and assessing the clinical benefit. jama dermatol. 2020;156(9):1004-1011. 3 kwatra sg, hines h, semenov yr, trotter sc, holland e, leachman s. a dermatologist's guide to implementation of gene expression profiling in the management of melanoma. j clin aesthet dermatol. 2020;13(11 suppl 1):s3-s14. 3 litchman gh, prado g, teplitz rw, et al. (2020). a systematic review and meta-analysis of gene expression profiling for primary cutaneous melanoma prognosis. skin the journal of cutaneous medicine, 4(3), 221–237. 1 skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 561 table 2. strength of recommendation taxonomy (sort) level of evidence for articles pertaining to the 11-gep test. article level of evidence articles reporting data on validity, accuracy, or clinical utility amaral tms, hoffmann mc, sinnberg t, et al. clinical validation of a prognostic 11-gene expression profiling score in prospectively collected ffpe tissue of patients with ajcc v8 stage ii cutaneous melanoma. eur j cancer. 2020;125:38-45. 1 marchetti ma, coit dg, dusza sw, et al. performance of gene expression profile tests for prognosis in patients with localized cutaneous melanoma: a systematic review and meta-analysis. jama dermatol. 2020;156(9):953-962. 1 systematic reviews or consensus guidelines grossman d, okwundu n, bartlett ek, et al. prognostic gene expression profiling in cutaneous melanoma: identifying the knowledge gaps and assessing the clinical benefit. jama dermatol. 2020;156(9):1004-1011. 3 kwatra sg, hines h, semenov yr, trotter sc, holland e, leachman s. a dermatologist's guide to implementation of gene expression profiling in the management of melanoma. j clin aesthet dermatol. 2020;13(11 suppl 1):s3-s14. 3 litchman gh, prado g, teplitz rw, et al. (2020). a systematic review and meta-analysis of gene expression profiling for primary cutaneous melanoma prognosis. skin the journal of cutaneous medicine, 4(3), 221–237. 1 skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 562 table 3. strength of recommendation taxonomy (sort) level of evidence for articles pertaining to the 8-gep + cp test. article level of evidence articles reporting data on validity, accuracy, or clinical utility bellomo d, arias-mejias sm, ramana c, et al. model combining tumor molecular and clinicopathologic risk factors predicts sentinel lymph node metastasis in primary cutaneous melanoma. jco precis oncol. 2020;4:319-334. 3 eggermont amm, bellomo d, arias-mejias sm, et al. identification of stage i/iia melanoma patients at high risk for disease relapse using a clinicopathologic and gene expression model. eur j cancer. 2020;140:11-18. 2 glazer a, tassavor m, portela d, et al. (2022). the integrated 31-gene expression profile test (i31-gep) for cutaneous melanoma outperforms the cp-gep at identifying patients who can forego sentinel lymph node biopsy when applying nccn guidelines. skin the journal of cutaneous medicine, 6(6), 474–481. 2 johansson i, tempel d, dwarkasing jt, et al. validation of a clinicopathological and gene expression profile model to identify patients with cutaneous melanoma where sentinel lymph node biopsy is unnecessary. eur j surg oncol. 2022;48(2):320-325. 2 mulder eeap, dwarkasing jt, tempel d, et al. validation of a clinicopathological and gene expression profile model for sentinel lymph node metastasis in primary cutaneous melanoma. br j dermatol. 2021;184(5):944-951. 2 mulder eeap, johansson i, grünhagen dj, et al. using a clinicopathologic and gene expression (cp-gep) model to identify stage i-ii melanoma patients at risk of disease relapse. cancers (basel). 2022;14(12):2854. 2 yousaf a, tjien-fooh fj, rentroia-pacheco b, et al. validation of cp-gep (merlin assay) for predicting sentinel lymph node metastasis in primary cutaneous melanoma patients: a u.s. cohort study. int j dermatol. 2021;60(7):851-856. 2 systematic reviews or consensus guidelines grossman d, okwundu n, bartlett ek, et al. prognostic gene expression profiling in cutaneous melanoma: identifying the knowledge gaps and assessing the clinical benefit. jama dermatol. 2020;156(9):1004-1011. 3 kwatra sg, hines h, semenov yr, trotter sc, holland e, leachman s. a dermatologist's guide to implementation of gene expression profiling in the management of melanoma. j clin aesthet dermatol. 2020;13(11 suppl 1):s3-s14. 3 litchman gh, prado g, teplitz rw, et al. (2020). a systematic review and meta-analysis of gene expression profiling for primary cutaneous melanoma prognosis. skin the journal of cutaneous medicine, 4(3), 221–237. 1 skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 563 2 evidence, and 2 were deemed to represent level 3 evidence. of the two papers that analyzed data from the 11-gep test, the panel designated both of them as level 1 evidence. of the 7 manuscripts that analyzed data from the 8-gep + cp test, 6 were designated as level 2 evidence and 1 was designated as level 3 evidence. consensus recommendations the panel then generated 11 consensus recommendations/statements related to indications for usage, all of which received a unanimous vote for adoption (table 4). each of the recommendations was then given a strength “a,” “b,”, or “c” according to sort criteria.14 usage guidelines: • integrating gep results can improve prognostic assessment for patients with t1a tumors at least 0.3mm in depth, t1b+ tumors, or any tumor in which there is significant uncertainty about adequacy of microstaging (e.g., positive deep margin) (sort level=a) • gep testing can identify a high-risk subset for recurrence, distant metastasis, or death of traditionally assessed low-risk patients (e.g., sln negative or t1a/b) (sort level=a) • gep testing provides clinically useful information that augments risk-aligned management decisions to both rule-in or rule-out the need for slnb and subsequent management plans (sort level=a) • adding gep results to clinicopathologic information significantly improves cm prognosis assessment (sort level=b) • adding gep results to ajcc classification improves prognostic assessment of cutaneous melanoma patients (sort level=b) • based on current literature, the gep tests have not been demonstrated to show prognostic utility for in-situ cm and ajcc8 stage iv disease and are not indicated for those patients (sort level=c). consensus supporting statements: • current literature supports that the 31gep test, with its more extensive evidence-driven data, offers more utility than other existing gep assays or nomograms (sort level=a) • integrating gep results can increase the precision and confidence of melanoma management decisions (e.g., follow up regimens, decision for slnb, referral to other specialties, and need for imaging) (sort level=b) • model prediction variance does impact clinical test utility (sort level=c). • gep results can be integrated into management decisions for patients being considered for adjuvant therapy (sort level=c). • based on the strength of the available literature, gep results should be considered as a criterion for randomization and inclusion of patients to improve the validity of cm clinical trials (sort level=c). gep testing has become an accepted clinical tool to aid in the prognostic assessment of numerous malignancies, including skin, breast, lung, colorectal, and prostate cancer.3 its use in cm is already commonplace, with data from over 1,000 31-gep cm tests in the us currently being integrated into patient management decisions every month.25 discussion skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 564 table 4. consensus statements and recommendations for incorporating gep testing into clinical practice and their corresponding strength using sort criteria. recommendation strength of recommendation consensus vote usage guidelines integrating gep results can improve prognostic assessment for patients with t1a tumors at least 0.3mm in depth, t1b+ tumors, or any tumor in which there is significant uncertainty about adequacy of microstaging (e.g., positive deep margin) a 6/6 gep testing can identify a high-risk subset for recurrence, distant metastasis, or death of traditionally assessed low-risk patients (e.g., sln negative or t1a/b) a 6/6 gep testing provides clinically useful information that augments risk-aligned management decisions to both rule-in or rule-out the need for slnbx and subsequent management plans a 6/6 adding gep results to clinicopathologic information significantly improves cm prognosis assessment b 6/6 adding gep results to ajcc classification improves prognostic assessment of cutaneous melanoma patients b 6/6 based on current literature, the gep tests have not been demonstrated to show prognostic utility for in-situ cm and ajcc8 stage iv disease c 6/6 consensus supporting statements current literature supports that the 31-gep test, with its more extensive evidence-driven data, offers more utility than other gep assays or nomograms a 6/6 integrating gep results can increase the precision and confidence in melanoma management decisions (e.g., follow up regimens, referral to other specialties, and need for imaging) b 6/6 model prediction variance does impact clinical test utility. c 6/6 gep results can be integrated into management decisions for patients being considered for adjuvant therapy c 6/6 based on the strength of the available literature, gep results should be considered as a criterion for randomization and inclusion of patients to improve the validity of cm clinical trials c 6/6 skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 565 despite multiple validation and clinical utility studies in the literature, there remains a lack of integration of gep testing into some of the formal models and guidelines for cm management. the ajcc8 prognostic model only uses breslow depth, ulceration status, and sentinel node positivity to distinguish between stage i-iii cm and does not mention a tumor’s genetic profile.47 furthermore, routine gep testing is not currently incorporated into nccn48 or aad49 cm management recommendations. gep tests are important tools as they can provide substantial prognostic information. the expand and integrate trials were two multi-center prospective clinical studies that demonstrated that the 31-gep test is able to further stratify patients beyond ajcc8 staging in patients with stage i-iii cm.26 these studies found that patients with a 31gep class 2 result had significantly lower 3year recurrence free survival (rfs) than those with a class 1 result (83% vs 97%, p < 0.0001).26 additionally, cms with a class 2 result had lower distant metastasis free survival (dmfs) (87% vs 99%, p < 0.0001) and overall survival (os) (90% vs 98%, p = 0.01) compared to those with a class 1 result.26 a retrospective validation study of the 11-gep test in stage ii cm showed that patients with a high gep score (geps) had a significantly lower 5-year melanomaspecific survival (mss) and 10-year mss compared to patients with a low geps (82% vs 92% and 67% vs 92%, p = 0.018).11 furthermore, in a multi-center retrospective cohort study with 837 patients, the 8-gep + cp test identified a high-risk patient group (47% of total stage i/iia patients) that had a much worse five-year rfs than the low-risk patient group (74% vs 89%; hr = 2.98; p<0.0001).5 the information provided by these tests can also further guide clinical management plans, such as the decision to perform a sentinel lymph node biopsy (slnb). according to nccn guidelines, slnb is not recommended for patients with a < 5% chance of a positive node, should be discussed and considered for patients with a 5-10% chance of a positive node, and should be discussed and offered to patients with a > 10% chance of sln positivity.48 while sentinel lymph node positivity is a key prognostic marker, studies have shown that < 20% of patients who undergo the biopsy are found to have nodal metastasis.50 given that the procedure has a > 10% risk of complications such as bleeding, infection, pain, neuropathy, lymphocele, lymphatic fistula, and lymphedema4, identifying patients that can safely forego the biopsy can significantly reduce morbidity. a multi-center validation study of the i-31 gep test (a test that integrates the 31-gep with clinicopathological features including breslow thickness, mitotic rate, ulceration status, and patient age) showed that the test increased the proportion of patients with t1t4 tumors predicted to have <5% risk of slnb positivity from 8.5% to 27.7% with a negative predictive value (npv) of 98%.41 moreover, for patients with t1 tumors originally classified to have a likelihood of slnb positivity of 5-10%, the i31-gep was able to reclassify 63% of these cases as either having < 5% or >10% risk of positive slnb41, a valuable distinction to help guide the decision of whether or not the procedure is necessary. for the 8-gep + cep test, a validation study analyzing the test’s ability to predict slnb positivity found that this model has a npv of 90.5% (95% confidence interval [ci]: 77.9-96.2%) in t1-4 cms.44 in comparing the three gep tests, the panel consensus was that there were significantly more studies supporting the validity, accuracy, and clinical utility of the 31-gep test compared to the 11-gep and 8-gep + skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 566 cp tests (22 studies validating the 31-gep test4,19-24,26-31,34-42, compared to just 2 studies validating the 11-gep test11,34 and 7 studies validating the 8-gep + cp test5,13,23,43-46). based on the limited studies for the 8-gep + cp and the 11-gep test, the panel concluded that there was insufficient data to assess their validity and utility or currently recommend usage in the clinical setting until further studies are performed. within the reviewed set of papers, there were studies showing head-to-head superiority of the 31-gep test over other tests. a retrospective comparison of the i31-gep test and the 8-gep + cp test showed that the i31gep had a 30:1 true-to-false-negative slnb ratio compared to a 15:1 ratio for the 8-gep + cp test.23 another study found that the i31-gep test was able to outperform an online nomogram from the melanoma institute of australia (mia)51 given the wide variance of that model’s prediction,4 which may not be actionable within nccn guideline parameters. in comparing this nomogram with the i31-gep in a retrospective cohort of 582 patients, the i-31gep was able to identify 28.5% of patients as having a <5% risk of slnb positivity while also having an upper 95% ci ≤ 10% compared with only a 0.9% (p<0.001) when using the mia nomogram.4 furthermore, for patients with a pre-test probability of slnb positivity between 510%, the i-31gep reclassified 60.2% (171/284) of cases as representing < 5% or > 10% risk compared to 13.7% (39/284, p<0.001) using the mia nomogram.4 this panel review has several limitations. the recommendations created by the panel did not take into account the cost of these tests or their impact on healthcare spending, but some studies have shown cost-effectiveness of gep tests.40,52 also, this panel consensus was designed to provide an update from a prior expert consensus10 that reviewed the available literature existent at that time. this current consensus is based specifically upon articles that were published subsequent to that article. cm represents a significant public health concern, as it has a rising incidence and material mortality rate despite advances in diagnosis and therapy. additional tools to aid in prognostic assessment and risk-aligned management decisions have the potential to significantly reduce morbidity, mortality, and healthcare costs. significant peer-reviewed literature exists supporting the incorporation of genomics into cm clinical assessment and management. the expert consensus guidelines and support statements presented here will hopefully provide a framework for the clinician to integrate gep testing into their cm patient management. the recommendations created by this expert consensus panel have been adopted as an official policy recommendation by the national society for cutaneous medicine. conflict of interest disclosures: dz, nb, ds and gl, and gg have no conflicts. bb is a consultant to castle biosciences, inc., leo pharma, and sun pharma. rc has served on advisory boards for castle biosciences. ml is an employee of mount sinai and receives research funds from: abbvie, amgen, arcutis, avotres, boehringer ingelheim, cara therapeutics, dermavant sciences, eli lilly, incyte, janssen research &amp; development, llc, ortho dermatologics, regeneron, and ucb, inc., and is a consultant for aditum bio, almirall, altrubio inc., anaptysbio, arcutis, inc., arena pharmaceuticals, aristea therapeutics, avotres therapeutics, biomx, brickell biotech, boehringer-ingelheim, bristol-myers squibb, cara therapeutics, castle biosciences, celltrion, corevitas, dermavant sciences, evommune, inc., facilitatation of international dermatology education, forte biosciences, foundation for research and education in dermatology, hexima ltd., leo pharma, meiji seika conclusion skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 567 pharma, mindera, pfizer, seanergy, trevi, and verrica. funding: this study was funded in part by an unrestricted educational grant from castle biosciences. corresponding author: danny zakria, md, mba 234 e 85th st. 5th floor new york, ny 10028 phone: (212) 731-3311 email: dzakria13@gmail.com references: 1. dzwierzynski ww. melanoma risk factors and prevention. clin plast surg. 2021;48(4):543-550. doi:10.1016/j.cps.2021.05.001 2. o'neill ch, scoggins cr. melanoma. j surg oncol. 2019;120(5):873-881. doi:10.1002/jso.25604 3. farberg as, marson jw, glazer a, et al. expert consensus on the use of prognostic gene expression profiling tests for the management of cutaneous melanoma: consensus from the skin cancer prevention working group. dermatol ther (heidelb). 2022;12(4):807-823. doi:10.1007/s13555-022-00709-x 4. zakria d, brownstone n, rigel d. (2022). the integrated 31-gene expression profile (i31-gep) test for cutaneous melanoma outperforms a clinicopathologic-only nomogram at identifying patients who can forego sentinel lymph node biopsy. skin the journal of cutaneous medicine, 6(6), 463–473. doi:10.25251/skin.6.6.3 5. eggermont amm, bellomo d, arias-mejias sm, et al. identification of stage i/iia melanoma patients at high risk for disease relapse using a clinicopathologic and gene expression model. eur j cancer. 2020;140:11-18. doi:10.1016/j.ejca.2020.08.029 6. hyams dm, cook rw, buzaid ac. identification of risk in cutaneous melanoma patients: prognostic and predictive markers. journal of surgical oncology 2019;119:175-86. 7. clarke le, warf mb, flake dd, 2nd, et al. clinical validation of a gene expression signature that differentiates benign nevi from malignant melanoma. journal of cutaneous pathology 2015;42:244-52. 8. gerami p, yao z, polsky d, et al. development and validation of a noninvasive 2-gene molecular assay for cutaneous melanoma. journal of the american academy of dermatology 2017;76:11420.e2. 9. maetzold d. castle biosciences announces medicare coverage for the decisiondxmelanoma test in cutaneous melanoma. news release. castle biosciences inc; october 18, 2018. accessed december 18, 2022.https://skinmelanoma.com/castlebiosciences-announces-medicare-coveragedecisiondx-melanoma-test-cutaneous-melanoma/ 10. berman b, ceilley r, cockerell c, et al. 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(2022). the integrated 31-gene expression profile test (i31-gep) for cutaneous melanoma outperforms the cp-gep at identifying patients who can forego sentinel lymph node biopsy when applying nccn guidelines. skin the journal of cutaneous medicine, 6(6), 474–481. doi:10.25251/skin.6.6.4 24. greenhaw bn, covington kr, kurley sj, et al. molecular risk prediction in cutaneous melanoma: a meta-analysis of the 31-gene expression profile prognostic test in 1,479 patients. j am acad dermatol. 2020;83(3):745-753. doi:10.1016/j.jaad.2020.03.053 25. grossman d, okwundu n, bartlett ek, et al. prognostic gene expression profiling in cutaneous melanoma: identifying the knowledge gaps and assessing the clinical benefit. jama dermatol. 2020;156(9):1004-1011. doi:10.1001/jamadermatol.2020.1729 26. hsueh ec, debloom jr, lee jh, et al. longterm outcomes in a multicenter, prospective cohort evaluating the prognostic 31-gene expression profile for cutaneous melanoma. jco precis oncol. 2021;5:po.20.00119. published 2021 apr 6. doi:10.1200/po.20.00119 27. hyams dm, covington kr, johnson ce, plasseraud km, cook rw. integrating the melanoma 31-gene expression profile test with surgical oncology practice within national guideline and staging recommendations. future oncol. 2021;17(5):517-527. doi:10.2217/fon2020-0827 28. jarell a, skenderis b, dillon ld, et al. the 31gene expression profile stratifies recurrence and metastasis risk in patients with cutaneous melanoma. future oncol. 2021;17(36):50235031. doi:10.2217/fon-2021-0996 29. jarell a, gastman br, dillon ld, et al. optimizing treatment approaches for patients with cutaneous melanoma by integrating clinical and pathologic features with the 31-gene expression profile test. j am acad dermatol. 2022;87(6):1312-1320. doi:10.1016/j.jaad.2022.06.1202 30. kangas-dick aw, greenbaum a, gall v, et al. evaluation of a gene expression profiling assay in primary cutaneous melanoma. ann surg oncol. 2021;28(8):4582-4589. doi:10.1245/s10434-020-09563-7 31. keller j, schwartz tl, lizalek jm, et al. prospective validation of the prognostic 31-gene expression profiling test in primary cutaneous melanoma. cancer med. 2019;8(5):2205-2212. doi:10.1002/cam4.2128 32. kwatra sg, hines h, semenov yr, trotter sc, holland e, leachman s. a dermatologist's guide to implementation of gene expression profiling in the management of melanoma. j clin aesthet dermatol. 2020;13(11 suppl 1):s3-s14. 33. litchman gh, prado g, teplitz rw, et al. (2020). a systematic review and meta-analysis of gene expression profiling for primary cutaneous melanoma prognosis. skin the journal of cutaneous medicine, 4(3), 221–237. doi:10.25251/skin.4.3.3 34. marchetti ma, coit dg, dusza sw, et al. performance of gene expression profile tests for prognosis in patients with localized cutaneous melanoma: a systematic review and meta-analysis. jama dermatol. 2020;156(9):953962. doi:10.1001/jamadermatol.2020.1731 35. marchetti ma, dusza sw, bartlett ek. utility of a model for predicting the risk of sentinel lymph node metastasis in patients with cutaneous melanoma. jama dermatol. 2022;158(6):680683. doi:10.1001/jamadermatol.2022.0970 36. martin bj, covington kr, quick ap, cook rw. risk stratification of patients with stage i cutaneous melanoma using 31-gene expression profiling. j clin aesthet dermatol. 2021;14(9):e61-e63. skin january 2023 volume 7 issue 1 (c) 2022 the authors. published by the national society for cutaneous medicine. 569 37. podlipnik s, boada a, lópez-estebaranz jl, et al. using a 31-gene expression profile test to stratify patients with stage i-ii cutaneous melanoma according to recurrence risk: update to a prospective, multicenter study. cancers (basel). 2022;14(4):1060. published 2022 feb 19. doi:10.3390/cancers14041060 38. podlipnik s, carrera c, boada a, et al. early outcome of a 31-gene expression profile test in 86 ajcc stage ib-ii melanoma patients. a prospective multicentre cohort study. j eur acad dermatol venereol. 2019;33(5):857-862. doi:10.1111/jdv.15454 39. thorpe rb, covington kr, caruso hg, et al. development and validation of a nomogram incorporating gene expression profiling and clinical factors for accurate prediction of metastasis in patients with cutaneous melanoma following mohs micrographic surgery. j am acad dermatol. 2022;86(4):846-853. doi:10.1016/j.jaad.2021.10.062 40. vetto jt, hsueh ec, gastman br, et al. guidance of sentinel lymph node biopsy decisions in patients with t1-t2 melanoma using gene expression profiling. future oncol. 2019;15(11):1207-1217. doi:10.2217/fon-20180912 41. whitman ed, koshenkov vp, gastman br, et al. integrating 31-gene expression profiling with clinicopathologic features to optimize cutaneous melanoma sentinel lymph node metastasis prediction. jco precis oncol. 2021;5:po.21.00162. published 2021 sep 13. doi:10.1200/po.21.00162 42. wisco oj, marson jw, litchman gh, et al. improved cutaneous melanoma survival stratification through integration of 31-gene expression profile testing with the american joint committee on cancer 8th edition staging. melanoma res. 2022;32(2):98-102. doi:10.1097/cmr.0000000000000804 43. johansson i, tempel d, dwarkasing jt, et al. validation of a clinicopathological and gene expression profile model to identify patients with cutaneous melanoma where sentinel lymph node biopsy is unnecessary. eur j surg oncol. 2022;48(2):320-325. doi:10.1016/j.ejso.2021.11.010 44. mulder eeap, dwarkasing jt, tempel d, et al. validation of a clinicopathological and gene expression profile model for sentinel lymph node metastasis in primary cutaneous melanoma. br j dermatol. 2021;184(5):944-951. doi:10.1111/bjd.19499 45. mulder eeap, johansson i, grünhagen dj, et al. using a clinicopathologic and gene expression (cp-gep) model to identify stage i-ii melanoma patients at risk of disease relapse. cancers (basel). 2022;14(12):2854. published 2022 jun 9. doi:10.3390/cancers14122854 46. yousaf a, tjien-fooh fj, rentroia-pacheco b, et al. validation of cp-gep (merlin assay) for predicting sentinel lymph node metastasis in primary cutaneous melanoma patients: a u.s. cohort study. int j dermatol. 2021;60(7):851-856. doi:10.1111/ijd.15594 47. gershenwald je, scolyer ra, hess kr, et al. melanoma staging: evidence-based changes in the american joint committee on cancer eighth edition cancer staging manual. ca cancer j clin. 2017;67(6):472-492. https://doi.org/10.3322/caac.21409 48. national comprehensive cancer network. melanoma: cutaneous (version 2.2021). https://www.nccn.org/professionals/physician_gls /pdf/cutaneous_melanoma.pdf. accessed 4 jan 2023. 49. swetter sm, tsao h, bichakjian ck, et al. guidelines of care for the management of primary cutaneous melanoma. j am acad dermatol. 2019;80(1):208-250. doi:10.1016/j.jaad.2018.08.055 50. morton dl, thompson jf, cochran aj, et al: final trial report of sentinel-node biopsy versus nodal observation in melanoma. n engl j med 370:599-609, 2014 51. lo sn, ma j, scolyer ra, et al. improved risk prediction calculator for sentinel node positivity in patients with melanoma: the melanoma institute australia nomogram. j clin oncol. 2020;38(24):2719-2727. doi:10.1200/jco.19.02362 52. hornberger j, siegel dm. economic analysis of a noninvasive molecular pathologic assay for pigmented skin lesions. jama dermatology 2018;154:1025-31. https://doi.org/10.3322/caac.21409 https://www.nccn.org/professionals/physician_gls/pdf/cutaneous_melanoma.pdf.%20accessed%204%20jan%202023 https://www.nccn.org/professionals/physician_gls/pdf/cutaneous_melanoma.pdf.%20accessed%204%20jan%202023 https://www.nccn.org/professionals/physician_gls/pdf/cutaneous_melanoma.pdf.%20accessed%204%20jan%202023 ¾ 356 subjects were randomized to dfd-01, 90 subjects to augbd, and 182 subjects to vehicle. ¾ individual sign scores all showed improvement with treatment, and dfd-01 showed significantly greater effect than augbd at day 4 for erythema (23.6% vs 12.2%, p=.021) and scaling (39.6% vs 25.6%, p=.014) (figure 1). ¾ reduction in tss was greater with dfd-01 than with augbd at day 4 (-17.3% vs -10.6%, p=.009) (figure 2). ¾ at day 4 dfd-01 was also significantly different from augbd for both tss50 (13.2% vs 5.6%, p=.044) and tss≤1 for any sign (13.8% vs 5.6%, p=.031). dfd-01, a vca midpotent betamethasone dipropionate 0.05% emollient-like spray formulation, demonstrates earlier onset of action compared with a super potent topical steroid for the treatment of moderate psoriasis leon kircik, md1; jonathan s. weiss, md2; kent allenby, md3 1dermresearch, pllc, louisville, ky; 2gwinnett dermatology, snellville, ga; 3promius pharma, a subsidiary of dr. reddy’s laboratories, princeton, nj introduction ¾ typically, topical steroids that are considered super potent by vasoconstrictor assay (vca) have demonstrated the highest efficacy along with a higher potential for hpa axis suppression. ¾ dfd-01, a vca midpotent topical steroid, [sernivo™ (betamethasone dipropionate) spray, 0.05%], approved for the treatment of mild to moderate plaque psoriasis in adults, was formulated to achieve a balance of steroid penetration to and persistence within the dermis and epidermis while minimizing absorption into the systemic circulation. ¾ dfd-01, an emollient-like spray formulation was compared with a super potent augmented betamethasone dipropionate 0.05% steroid lotion (augbd) for the treatment of moderate plaque psoriasis. ¾ early response to treatment is the focus of this post hoc analysis conclusions ¾ midpotent dfd-01 (betamethasone dipropionate 0.05% spray) showed efficacy on global measures of iga, tss and tss50 with significant improvement at day 4 on all outcomes compared to baseline ¾ at day 4 tss improvement was greater with dfd-01 compared with super potent augmented betamethasone dipropionate 0.05% lotion. methods figure 1. pooled analysis of early onset of relief of erythema and scaling ¾ data from two phase 3, randomized, clinical trials enrolling adults with moderate plaque psoriasis (iga=3; 10% to 20% bsa) were pooled. ¾ subjects were randomized to receive dfd-01, augbd, or vehicle spray (vehicle) and products were applied to all affected areas on the body excluding face, scalp, and intertriginous areas twice daily for 14 or 29 days. dfd-01 was applied for 29 days and augbd was applied for 14 days per their respective labels. ¾ treatment success at days 4 and 8 was defined as iga=0 or 1 and ≥2 grade improvement from baseline. ¾ reduction in total sign score (tss) for a target lesion (the sum of erythema, plaque and elevation scores), individual sign scores, tss50 and tss≤1 for any sign, were also assessed. analysis was by fisher’s exact test. financial support: this study was funded by the dr. reddy’s laboratories group of companies. drl publication # 794 results figure 2. pooled analysis reduction in tss fc17posterpromiuskircikdfdearlyonset.pdf microsoft word september 2020 comp 952 proof.docx skin september 2020 volume 4 issue 5 copyright 2020 the national society for cutaneous medicine 483 compelling comments falling in hair love comes naturally emmanuella oduguwa, bs1, danyal tahseen, bs2 1university of texas southwestern medical center, dallas, tx 2university of texas health science center at houston, mcgovern medical school, houston, tx afro-textured hair refers to the spectrum of naturally curly hair occurring in african-american, afro-caribbean and indigenous african women. the retro-curvature of the bulb and elliptical shaft in afro-textured hair contrast to the straight shape of hair follicles common among caucasians.1 although wearing afro-textured hair in natural styles, such as afros, protects hair from potentially harmful chemical treatments, social stigmas discourage natural styles.1,2 an example of discrimination against afro-ethnic hair in popular media occurred in 2015, when a fashion critic compared black actress zendaya’s dreadlocks to the smell of marijuana. discrimination against afrotextured hair may lead black women to seek chemical hair-straighteners more than women from other racial/ethnic groups, contributing to burden of hair and scalp dermatoses.2 the dermatology community should be aware of these concerns, because our efforts may motivate black female patients to seek dermatological care. in recent years, mainstream media, such as disney’s 2020 film hair love, issa rae’s insecure, covid-19-related instagram hashtags like #quarantinecurls, and dermatology-related accounts like @brownskinderm have increased visibility of afro-textured hair. although there is heightened awareness for natural hair, black women report dissatisfaction with the degree of knowledge that physicians specializing in hair have about the complexity of afro-textured hair.3 dermatologists play an integral role in black women’s journey to disentangle social stigmas and clinically treat indications that impose barriers to maintaining natural hair styles. the dermatology community has the unique opportunity to advocate for hair equity among black patients and dispel common misconceptions (e.g. increased clinical research, certified dermatologist-led twitter accounts), following precedents set by experts in the field including dr. crystal aguh. medical schools and dermatology residency training programs may augment instruction on afro-textured hair in their curricula. dermatologists may partner up with black hair stylists to conduct educational sessions for clients on haircare management, perhaps including medical students for dermatologist-supervised cultural competency training. our increasingly diverse population requires that dermatologists adapt to the unique needs of black patient and highlight the beauty of healthy, afro-textured hair. rather than perpetuating the damaging belief that afro-textured hair is too different or difficult to manage, we should empower black women to embrace their natural curls and acknowledge the diversity in all variations of afro-textured hair. conflict of interest disclosures: none funding: none corresponding author: danyal tahseen mcgovern medical school university of texas health science center at houston 6431 fannin st houston, tx email: danyal.tahseen@uth.tmc.edu references: 1. tanus a, oliveira ccc, villarreal djv, sanchez fav, dias mfrg. black women’s hair: the main scalp dermatoses and aesthetic practices in women of african ethnicity. an bras dermatol. 2015;90(4):450-467. doi:10.1590/abd18064841.20152845 2. zota ar, shamasunder b. the environmental injustice of beauty: framing chemical exposures from beauty products as a health disparities concern. am j obs gynecol. 2017;217(4):139-148. doi:10.1016/j.physbeh.2017.03.040 3. gathers rc, mahan mg. african american women, hair care, and health barriers. j clin aesthet dermatol. 2014;7(9):26-29. powerpoint presentation once-daily oral sarecycline 1.5 mg/kg/day is effective for moderate to severe acne vulgaris results from two 12-week, phase 3, randomized, double-blind clinical trials angela moore, md; lawrence green, md2, suzanne bruce, md; neil sadick, md; eduardo tschen, md, mba; philip werschler, md, faad, faacs; sunil dhawan, md; douglas forsha, md; michael gold, md, faad; scott guenthner, md; steve kempers, md; leon kircik, md; jennifer parish, md; marta rendon, md; phoebe rich, md; linda stein-gold, md; stephen tyring, md, phd; robert weiss, md, faad; adnan nasir, md; carsten schmitz, md, phd; terry boodhoo, ms; alexandre kaoukhov, md; david berk, md; fran cook-bolden, md; ayman grada, md, ms email: ayman.grada@almirall.com introduction  oral broad-spectrum tetracycline-class antibiotics are prescribed for the treatment of moderate to severe inflammatory acne  poor tolerability and bacterial resistance concerns may limit the use of broad-spectrum tetracycline antibiotics for the treatment of acne conclusions sarecycline, a narrow-spectrum tetracycline class antibiotic, fda-approved for the treatment of moderate to severe acne in ages 9 and older, was safe, well tolerated, and statistically significant at 12 weeks in achieving iga success (defined as ≥2-grade improvement and score 0 [clear] or 1 [almost clear]) and reduction in inflammatory lesion count. design & methodology male and female aged 9 to 45 years between 33 kg and 136 kg results financial support: this study was funded and sponsored by allergan. sarecycline is owned and marketed by almirall, llc. ussey0277 sc1401 sc1402 outcome measure sarecyclinen =483 placebo n = 485 p sarecycline n = 519 placebo n = 515 p iga success* 21.9% 10.5% 0.0001 22.6% 15.3% 0.0038 mean percent reduction in inflammatory lesions 52.2% 35.2% 0.0001 50.8% 36.4% 0.0001 *note: iga success defined as ≥2-grade improvement and score 0 [clear] or 1 [almost clear] table 1. iga success and inflammatory lesion efficacy at week 12  to evaluate the efficacy and safety of sarecycline, a once-daily, narrow-spectrum tetracycline-class drug in moderate to severe acne objective moderate to severe (iga ≥ 3) facial acne 20 – 50 inflammatory lesions ≤ 100 noninflammatory lesions ≤ 2 nodules  two phase 3 multicentre, randomized, double-blind, placebo-controlled, parallel group studies.  up to 35 day screening period to establish eligibility and baseline  12 week double-blind treatment with study visits at 3, 6, 9, and 12 weeks subjects randomized 1:1 to sarecycline 1.5 mg/kg/day oral or placebo in sc1401 and sc1402 (table 1) iga success rates were 21.9% and 22.6% (sarecycline) versus 10.5% and 15.3% (placebo; p < .0001 and p = .0038). onset of efficacy in inflammatory lesion reduction occurred as early as week 3, with mean percentage reduction in inflammatory lesions at week 12 in sc1401 and sc1402 of 52.5% and 50.8% (sarecycline) versus 35.2% and 36.4% (placebo) (figs 1 & 2). efficacy on truncal acne in (fig 3). adverse events ≥ 2% in any group are shown in table 2.  co-primary efficacy endpoints:  absolute change in facial inflammatory lesion count at week 12  iga success – iga score of 0 (clear) or 1 (almost clear) and ≥ 2 point improvement from baseline  secondary endpoints included absolute and percent change from baseline in inflammatory lesions at weeks 3, 6, & 9. table 2. adverse events ≥ 2% in any group sc1401 sc1402 teaes sarecycline n = 481 placebo n = 483 teaes sarecycline n = 513 placebo n = 513 nausea nasopharyngitis headache vomiting 4.6% 3.1% 2.7% 2.1% 2.5% 2.9% 2.7% 1.4% nasopharyngitis headache 2.5% 2.9% 2.9% 4.9% baseline week 3 week 12 vestibular, phototoxic, vulvovaginal candidiasis, and mycotic infections ≤1.1% in sarecycline treated patients. gastrointestinal teae rates were low baseline week 3 week 12 reference: moore a, green lj, bruce s, et al. once-daily oral sarecycline 1.5 mg/kg/day is effective for moderate to severe acne vulgaris: results from two identically designed, phase 3, randomized, double-blind clinical trials. journal of drugs in dermatology: jdd. 2018 sep;17(9):987-96. fig 1 & 2. mean % reduction in inflammatory lesions fig 3. truncal acne: % of patients with iga success at wk 12 slide number 1 microsoft word september 2020 can 935 proof.docx skin september 2020 volume 4 issue 5 copyright 2020 the national society for cutaneous medicine 486 commentary & notes letter to the editor: commentary on “avoiding the hazards of ultraviolet light in the adolescent population” elise m. weisert, bs1, ethan d. hinds iii, bba1 1the university of texas medical branch, school of medicine, galveston, tx we read with great interest the article by auchus et al. that addressed adolescent sun protection, tanning behaviors, and the physician’s approach to challenging questions about sun protection in adolescents.1 auchus et al. describe the role of ultraviolet light in both acute and chronic skin conditions, including skin cancer and premature aging. they posit that adolescents tend to be unconcerned about skin cancer risk and suggest that physicians should instead inform adolescents about the signs of premature aging, including wrinkles and fine lines, associated with natural and artificial sun exposure. while adolescents frequently engage in tanning behaviors, often without adequate sun protection, their risk of premature aging goes beyond exposure to ultraviolet light. an emerging body of literature suggests that visible light exposure (400-700 nm) may also contribute to premature aging of the skin and hyperpigmentation.2 studies show these effects are secondary to the production of reactive oxygen species (ros).3 penetration of visible light into the dermis generates ros that upregulate proinflammatory cytokines and matrix metalloproteinases, causing skin inflammation that contributes to photoaging and collagen breakdown, respectively.3 though the sun is the largest producer of visible light, artificial sources of light also emit radiation, including televisions, led light, fluorescent light, and screens such as cell phones, computers, and tablets.4 their peak emission lies in the blue spectrum (400-490 nm).4 as the use of technology, especially smartphones and tablets, continues to propagate, adolescents receive more radiation than ever from electronic devices, even from camera flashes.4 the risk may even include children, who increasingly utilize electronics for games, school, and communication. in addition, visible light from artificial sources generates concern due to high exposure time and closer proximity compared to uv visible light. there are a number of methods to protect the skin from visible light damage, including barriers such as topical antioxidant serums or blue light filters for phones, tablets, and computers. many devices now also have settings to disable blue light in favor of yellow light, which were created to combat blue light-induced insomnia in users.5 standard uva/uvb protecting sunscreens appear to have inadequate effects on the ros produced by visible light, suggesting the need for fortification with topical antioxidants, which protect against oxidative skin september 2020 volume 4 issue 5 copyright 2020 the national society for cutaneous medicine 487 stress to the melanocytes.3,6 providing education to this young patient population about the possible benefits of utilizing a topical antioxidant serum on the face and neck when they apply daily sunscreen offers an opportunity for protection against skin cancers, as well as protection from premature aging and hyperpigmentation. although public health concerns for melanoma and other skin cancers are more well known, focused early education on the hazards of both uv and visible light may lead to lasting habits in adulthood. lastly, as auchus et al. suggested, framing the discussion around prevention of premature aging is likely the most effective strategy for patient compliance in the adolescent population. conflict of interest disclosures: none funding: none corresponding author: elise weisert, bs school of medicine the university of texas medical branch galveston, tx phone: 817-243-5019 email: emweiser@utmb.edu references: 1. auchus a, brodell rt, nahar vk, ward kh. avoiding the hazards of ultraviolet light in the adolescent population. skin the journal of cutaneous medicine. 2020;4(3):189-199. 2. duteil l, cardot-leccia n, queille-roussel c, et al. differences in visible light-induced pigmentation according to wavelengths: a clinical and histological study in comparison with uvb exposure. pigment cell & melanoma research. 2014;27(5):822-826. 3. liebel f, kaur s, ruvolo e, kollias n, southall md. irradiation of skin with visible light induces reactive oxygen species and matrix-degrading enzymes. journal of investigative dermatology. 2012;132(7):1901-1907. 4. arjmandi n, mortazavi g, zarei s, faraz m, mortazavi s. can light emitted from smartphone screens and taking selfies cause premature aging and wrinkles? journal of biomedical physics & engineering. 2018;8(4):447. 5. shechter a, kim ew, st-onge m-p, westwood aj. blocking nocturnal blue light for insomnia: a randomized controlled trial. journal of psychiatric research. 2018;96:196-202. 6. freitas jv, junqueira hc, martins wk, baptista ms, gaspar lr. antioxidant role on the protection of melanocytes against visible lightinduced photodamage. free radical biology and medicine. 2019;131:399-407. skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 297 short communications unique presentation of urticaria pigmentosa as a subcutaneous mass payvand kamrani, bs1, rachel giesey, do2, luisa christensen, md2, neil korman, md2, gregory r delost, do3 1philadelphia college of osteopathic medicine; philadelphia, pa 2department of dermatology; university hospitals cleveland medical center, cleveland, oh 3apex dermatology and skin surgery center; mayfield heights, oh urticaria pigmentosa (up) is one of the most common clinical variants of cutaneous mastocytosis. it can present clinically as multiple red-brown macules and rarely plaques and nodules. childhood cases have a good prognosis usually without systemic involvement.1 our case describes up uniquely presenting as a subcutaneous mass in the perineum of a pediatric patient. a 9-year-old male with history of tan-brown macules starting at age 4 with punch biopsy consistent with up (figure 2) was managed with antihistamines (levocetrizine and montelukast) and close observation until he presented with an asymptomatic lump of the right perineum with no skin surface change. an ultrasound revealed a 1.7 cm hypoechoic solid lesion (figure 1) for which excisional biopsy stained diffusely positive for cd68 and cd117, with rare positive s100 and cd1a cells, consistent with up. serum tryptase levels were within normal limits. the patient received antihistamines and full body 6-week uvb light treatment with significant improvement of his cutaneous lesions and complete resolution of the subcutaneous perennial mass. figure 1. ultrasound of the perineal lump revealed a 1.7cm hypoechoic solid lesion. figure 2. tan-brown macules involving the posterior auricular area, chest and abdomen. skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 298 urticaria pigmentosa (up) is the most common presentation of cutaneous mastocytosis in children.1 children typically present with widespread distribution of tan macules and rarely with nodules or plaques, most commonly on the trunk.1,5 it can present at birth but typically appears in infancy and childhood and gradually improves by adolescence. darier’s sign, urtication of up lesions following scratching, may occur.1 there have been few reports of female pediatric patients presenting with a single mastocytosis lesion in the vulvar regions, but no cases of mastocytosis presenting as a subcutaneous mass in the perineum of males have been reported in the literature.4,6 evaluation and diagnosis of up are often made clinically but can be confirmed with a biopsy. systemic tests are rarely needed but can be deemed useful if there is a concern of systemic mastocytosis involvement such as diarrhea, gastric ulcers, flushing reactions, headaches, and failure to thrive.5 these tests include a cbc with differential, complete chemistry panel, and serum tryptase level which would be elevated in systemic mastocytosis but negative in cutaneous mastocytosis.1 up that begins after age 10 usually persists and can be associated with systemic disease. treatment focuses on controlling symptoms associated with the lesions. h1 blockers can be effective against itching and flushing symptoms. topical steroids can also be used for symptomatic relief.1 phototherapy is a second-line therapy which may be considered when there is poor symptomatic control or progression of disease, such as what occurred in our patient. avoiding mast cell degranulation is another aim of therapy. physical granulators include temperature changes such as extreme heat or cold and mechanical factors such as trauma or irritation. chemical granulators include alcohol, aspirin, nsaids, and iodinated contrast media.1,5 precautions should be taken when placing a pediatric patient with up under systemic anesthesia. morphine and certain neuromuscular blockers such as rocuronium and atracurium should be avoided as they have been associated with a significant incidence of anaphylaxis due to mast cell degranulation.2,3 propofol is considered a safer recommendation for general anesthesia for patients with mastocytosis. other safe hypnotics agents include etomidate and ketamine.3 conflict of interest disclosures: none funding: none corresponding author: payvand kamrani philadelphia college of osteopathic medicine phone: 919-619-8369 fax: 609-357-9515 email: payvandkh@pcom.edu references: 1. briley ld, phillips cm. cutaneous mastocytosis: a review focusing on the pediatric population. clinical pediatrics. 2008;47(8):757761. 2. dewachter p, castells mc, hepner dl, moutonfaivre c. perioperative management of patients with mastocytosis. anesthesiology: the journal of the american society of anesthesiologists. 2014;120(3):753-759. 3. klein nj, misseldine s. anesthetic considerations in pediatric mastocytosis: a review. journal of anesthesia. 2013;27(4):588-598 4. serarslan, gamze, esin atik, and s. zeteroglu. "nodular mastocytosis of the vulva: an unusual localisation." australian and new zealand journal of obstetrics and gynaecology 45.4 (2005): 335336. 5. zitelli, basil j., sara c. mcintire, and andrew j. nowalk. zitelli and davis' atlas of pediatric physical diagnosis e-book: expert consultmailto:payvandkh@pcom.edu skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 299 online. elsevier health sciences, 2017:8, 275340. 6. shuangshoti s, shuangshoti s, pintong j, piyayotai v, sukpanichnant s. solitary mastocytoma of the vulva: report of a case. int j gynecol pathol. 2003; 22: 401– 403. 2019_fallclinical_ct010_final.cdr photodynamic therapy with bf-200 ala for the treatment of mild to severe actinic keratosis on extremities and trunk/neck: results of a randomized phase iii trial authors: t. dirschka , m. ulrich , u. reinhold , r. dominicus , r. aschoff , r.-m. szeimies 1 2 3 4 5 6 conclusions n high efficacy for ak treatment on extremities, trunk and neck: superiority of bf-200 ala over placebo n pdt with bf-200 ala is well-tolerated n overall cosmetic outcome of pdt with bf-200 ala is superior over placebo (p<0.0001, one-sided wilcoxon signed rank test) trial protocol actinic keratosis objectives n the pivotal phase iii study (eudract 2017-000486-72) was performed to characterize the efficacy and safety profile of bf-200 ala compared to ® placebo in the treatment of mild to severe ak lesions located on the extremities and trunk/neck with pdt when using the bf-rhodoled lamp, a narrowband, red light illumination source. medication n bf-200 ala gel (contains 10% ala hydrochloride equivalent to 7.8% 5-aminolevulinic acid (ala)) n placebo to bf-200 ala gel patients & treatment procedure n randomized, double-blind, intra-individual phase iii trial was performed in 6 sites in germany n 50 patients with clinically mild to severe ak lesions on the extremities and trunk/neck were treated after randomization n illumination was performed 3h after drug application for 10 min with a narrowband red light source (~635 nm, 37 j/cm²) n in case of remaining lesions after first pdt, a second treatment was performed 12 weeks after pdt-1 n follow-up (fu): 6 and 12 months endpoints n primary endpoint: total lesion clearance rate in percent per patient’s side 12 weeks after the last pdt n secondary endpoints: different characteristics of lesions and the overall cosmetic outcome synopsis bf-200 ala is a gel containing 5-aminolevulinic acid hydrochloride (10%) in a nanoscale lipid vesicle formulation. it is approved under the brand ® name ameluz for lesionand field-directed ak treatment on face and scalp in the us and for treatment of mild to moderate ak on face and scalp and superficial and nodular basal cell carcinoma (bcc) in the eu. we herein report the results of a randomized phase iii trial investigating bf-200 ala in combination with red light for the treatment of mild to severe ak on extremities and trunk/neck. schematic overview: pdt for ak treatment on extremities and trunk/neck 1 2 3 institutes: centroderm gmbh, wuppertal, germany and faculty of health, university witten-herdecke, witten, germany; cmb collegium medicum berlin gmbh, berlin, germany, mvz dermatologisches zentrum bonn 4 5 6 gmbh, bonn, germany, proderma, dülmen, germany, department of dermatology, university hospital carl gustav carus, technical university dresden, dresden, germany, department of dermatology and allergology, klinikum vest gmbh, recklinghausen, germany mean total lesion clearance rate per patient‘s side, overall (a), extremities (b) and trunk/neck (c) a: bf-200 ala: 86.0%, placebo: 32.9% superiority of bf-200 ala over placebo (p<.0001, one-sided wilcoxon signed rank test) ; b: bf-200 ala: 83.5%, placebo: 27.1% superiority of bf-200 ala over placebo (p<.0001, one-sided wilcoxon signed rank test); c: bf-200 ala: 96.0%, placebo: 55.5% superiority of bf-200 ala over placebo (p=0.0156, one-sided wilcoxon signed rank test) n=50 treated side of extremities or trunk/neck bf-200 ala placebo not allocated to a specific patient‘s side side unknown any aes any serious aes any teaes any serious teaes any teaes leading to death any related teaes any teaes resulting in discontinuation of study 50 (100) 2 (4.0) 50 (100) 2 (4.0) 0 50 (100) 0 28 (56.0) 0 28 (56.0) 0 0 22 (44.0) 0 22 (44.0) 3 (6.0) 20 (40.0) 2 (4.0) 0 1 (2.0) 0 5 (10.0) 0 5 (10.0) 0 0 0 0 overview of adverse events saf: safety analysis set; ae: adverse event; teae: treatment-emergent adverse event overall cosmetic outcome 12 weeks after the last pdt [fas] bf-200 ala placebo 0 50 100 150 c o m p le te ly c le a re d le s io n s [% ] (n=49) (n=49) very good or good [%] satisfactory [%] unsatisfactory [%] impaired [%] 40.8 18.4 20.420.4 18.4 8.2 16.3 57.1 total lesion clearance per patient‘s side 12 weeks after the last pdt bf-200 ala placebo lesion preparation (including degreasing, roughening of the skin) application of bf-200 ala or placebo light-tight dressing; 3 h removal of remaining gel, illumination with narrowband red light source potential second pdt treatment fu 1 year assessment after 12 weeks due to ala pdt‘s mode of action, aes are mainly local application site reactions such as erythema, pain, edema, and irritation which are transient and self-limiting, normally within 1-2 weeks. this study is sponsored by biofrontera bioscience gmbh (germany). eudract 2017-000486-72 visit 1 (screening ) (<2 weeks before pdt-1) visit 2 (pdt-1) visit 3 (4 weeks post pdt-1) application of bf-200 ala and placebo plus illumination with a narrowband red light source for 10 min phone call (1 week post pdt-1) visit 4 (12 weeks post pdt-1; pdt-2) phone call (1 week post pdt-2) visit 5 (4 weeks post pdt-2) visit 6 (12 weeks post pdt-2) final assessment for partial or nonresponders fu 1 (6 months after pdt-1 / pdt-2) fu 2 (12 months after pdt-1 / pdt-2) final assessment for complete responders! in case of remaining lesions after first pdt, a second treatment was performed (partial or non-responders). bf-200 ala placebo 0 50 100 150 c o m p le te ly c le a re d l e s io n s [% ] (n=39) (n=39) extremities bf-200 ala placebo 0 50 100 150 c o m p le te ly c le a re d le s io n s [% ] (n=10) (n=10) trunk/neck a b c overall seite 1 acknowledgements: medical writing support was provided by prescott medical communications group (chicago, il) with financial support from ortho dermatologics | presented at the fall clinical dermatology conference • october 17-20, 2019 • las vegas, nv synopsis ◾ psoriasis is a chronic, immune-mediated disease that can have frequent exacerbations and remissions1,2 ◾ the use of topical therapy is a key component in the management of almost all psoriasis patients3 ◾ topicals are considered first-line therapy for mild disease3 and are having an increasing role in moderate-to-severe psoriasis as an integral part of combination therapy objective ◾ to investigate the efficacy, safety, and tolerability of a once-daily application of a fixed combination halobetasol propionate 0.01% and tazarotene 0.045% (hp/taz; duobrii™ ortho dermatologics, bridgewater, nj) lotion compared with its vehicle in patients with severe localized plaque psoriasis methods ◾ in two phase 3, multicenter, double-blind, vehicle-controlled studies (nct02462070 and nct02462122), patients were randomized (2:1) to receive hp/taz or vehicle once-daily for 8 weeks, with a 4-week posttreatment follow-up4 • in these studies, cerave® hydrating cleanser and cerave® moisturizing lotion (l’oreal, ny) were provided as needed for optimal moisturization/cleaning of the skin ◾ data from these studies were pooled and analyzed post hoc in participants with severe psoriasis (investigator global assessment [iga] of 4 and body surface area [bsa] of 3%–12%) ◾ efficacy assessments included treatment success (≥2-grade improvement from baseline in iga score and a score of ‘clear’ or ‘almost clear’ [primary endpoint]), impact on individual signs of psoriasis (erythema, plaque elevation, and scaling) at the target lesion, mean change in bsa and igaxbsa, and the proportion of patients achieving a clinically meaningful response (≥50% improvement in igaxbsa) ◾ safety and treatment-emergent adverse events (teaes) were evaluated throughout the study results ◾ a total of 62 participants with severe psoriasis (iga 4; mean bsa 7.4%) were included in this analysis ◾ by week 8, 34.8% of participants achieved treatment success with hp/taz compared with 0% on vehicle (p=0.004; figure 1) ◾ hp/taz lotion was also significantly superior in reducing psoriasis signs and symptoms and reducing bsa • at week 8, significantly more hp/taz-treated participants achieved ≥2-grade improvement in erythema (47.4%), plaque elevation (66.4%), and scaling (65.4%) compared with vehicle (14.0% [p=0.016], 14.8% [p<0.001], and 14.7% [p<0.001], respectively) • participants treated with hp/taz lotion achieved a 32.8% mean reduction from baseline in bsa, compared with a 39.6% increase with vehicle (p=0.013) ◾ hp/taz lotion demonstrated significantly greater reduction in igaxbsa compared to vehicle from week 2 onward (p<0.001; figure 2) • by week 8, the mean reduction in igaxbsa in hp/taz-treated participants was 52.9% compared with a mean increase of 17.5% in vehicle-treated participants (p<0.001) • most participants treated with hp/taz lotion achieved a clinically meaningful response (igaxbsa-50) efficacy, safety, and tolerability of a halobetasol 0.01%/tazarotene 0.045% fixed combination in the treatment of severe plaque psoriasis: post hoc analysis of two phase 3 randomized controlled trials mark g lebwohl, md1; jeffrey l sugarman, md, phd2; linda stein gold, md3; tina lin, pharmd4; gina martin, mot5 1icahn school of medicine at mount sinai, new york, ny; 2university of california, san francisco, ca; 3henry ford hospital, detroit, mi; 4ortho dermatologics, bridgewater, nj; 5bausch health americas, inc, petaluma, ca figure 1: percentage of participants with severe psoriasis achieving treatment successa by study visit (itt population; pooled data) 0% 30% 20% 10% 40% 50% 60% study visit (weeks) p e rc e n ta g e o f p a rt ic ip a n ts baseline 2 4 6 8 12 treatment posttreatment hp/taz (n=39) vehicle (n=23) *p<0.05 vs vehicle; **p<0.01 vs vehicle. a treatment success was defined as ≥2-grade improvement from baseline in iga score and a score of ‘clear’ or ‘almost clear’. hp/taz, halobetasol propionate 0.01% and tazarotene 0.045%; iga, investigator global assessment; itt, intent-to-treat. figure 2: mean percent change in igaxbsa by study visit in participants with severe psoriasis (itt population; pooled data) -60% -20% -40% -50% 0% 10% 20% study visit (weeks) p e rc e n t c h a n g e f ro m b a se lin e baseline 2 4 6 8 12 treatment posttreatment hp/taz (n=39) vehicle (n=23) -30% -10% **p<0.01 vs vehicle; ***p<0.001 vs vehicle. bsa, body surface area; hp/taz, halobetasol propionate 0.01% and tazarotene 0.045%; iga, investigator global assessment; itt, intent-to-treat. ◾ one participant (2.6%) treated with hp/taz lotion discontinued due to aes ◾ the most frequently reported treatment-related teaes with hp/taz were application site pain (7.9%), contact dermatitis (5.3%) and pruritus (5.3%; table 1) table 1: summary of treatment-emergent adverse events in participants with severe psoriasis through week 8 (safety population; pooled data) n (%) hp/taz lotion (n=38) vehicle lotion (n=23) participants reporting any teaes 18 (47.4) 8 (34.8) participants reporting any saes 0 0 deaths 0 0 participants discontinuing due to teaes 1 (2.6) 1 (4.3) severity of teaes mild 8 (21.1) 2 (8.7) moderate 9 (23.7) 5 (21.7) severe 1 (2.6) 1 (4.3) relationship to study drug related 8 (21.1) 3 (13.0) unrelated 10 (26.3) 5 (21.7) treatment-related teaes reported in ≥2% of participants application site pain 3 (7.9) 0 pruritis 2 (5.3) 1 (4.3) contact dermatitis 2 (5.3) 0 rash 1 (2.6) 0 skin atrophy 1 (2.6) 0 skin lesion 1 (2.6) 0 telangiectasia 1 (2.6) 0 wound secretion 1 (2.6) 0 skin irritation 0 1 (4.3) peripheral swelling 0 1 (4.3) pain in extremity 0 1 (4.3) burning sensation 0 1 (4.3) hp/taz, halobetasol propionate 0.01% and tazarotene 0.045%; sae, serious adverse event; teae, treatment-emergent adverse event. conclusion ◾ in patients with severe localized plaque psoriasis, hp/taz lotion provides rapid and sustained efficacy with good tolerability and safety over 8 weeks of once-daily use references 1. nestle fo, et al. n engl j med. 2009;361(5):496-509. 2. cohen sn, et al. clin exp dermatol. 2012;37 suppl 1:13-18. 3. menter a, et al. j am acad dermatol. 2009;60(4):643-659. 4. sugarman jl, et al. j drugs dermatol. 2018;17(8):855-861. author disclosures m lebwohl is an employee of mount sinai and receives research funds from abbvie, amgen, arcutis, astrazeneca, boehringer ingelheim, celgene, clinuvel, eli lilly, incyte, janssen research & development, llc, kadmon corp., llc, leo pharmaceuticals, medimmune, novartis, ortho dermatologics, pfizer, sciderm, ucb, inc., and vidac.; is a consultant for allergan, almirall, arcutis, inc., avotres therapeutics, birchbiomed inc., boehringer-ingelheim, bristol-myers squibb, cara therapeutics, castle biosciences, corrona, dermavant sciences, foundation for research and education in dermatology, inozyme pharma, leo pharma, meiji seika pharma, menlo, mitsubishi, neuroderm, pfizer, promius/dr. reddy’s laboratories, theravance, and verrica. j sugarman is a consultant for ortho dermatologics, bausch health, regeneron, sanofi, and pfizer. l stein gold is an investigator/consultant or speaker for ortho dermatologics, leo, dermavant, incyte, novartis, abbvie, and lilly. t lin is an employee of ortho dermatologics. g martin is an employee of bausch health americas inc. skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 56 brief articles “they won’t let me return to work.” a carpenter diagnosed with porphyria cutanea tarda max a. schafer, do1, maulik m. dhandha, md2, jonathan b. karnes, md2 1maine-dartmouth family medicine residency, augusta, me 2maine-dartmouth family medicine residency dermatology services, augusta, me a 46 year old white man with a past medical history of chronic untreated hepatitis c, alcohol abuse, 35 pack year smoking history, and a difficult socioeconomic situation presented to primary care clinic in a rural setting with concern over 6-7 months of recurrent, itchy, easily ruptured blisters and small white bumps. he was not on any medications. he denied any personal or family history of blistering disorders or other chronic skin conditions. lesions primarily occurred along the dorsum of hands and forearms, face, nose, and ears. he worked as a carpenter, often outdoors and the skin condition interfered with his livelihood. he was held out of work by his employer at time of presentation. physical exam revealed scattered 0.5-1.5 cm erosions and ulcerations with secondary crusting as well as milia, dyspigmentation, and scarring at sites of prior inflammation in photodistributed areas along the dorsum of the hands, forearms to mid upper arms (figure 1 and 2), face and ears. given the distribution and morphology of lesions as well as patient history of hepatitis c and alcohol use, there was high suspicion for porphyria cutanea tarda (pct). skin biopsy, serum and urine porphyrins testing, testing for hepatitis c viral load as well as hiv screening was also done. figure 1. scattered erosions and ulcerations, milia, and dyspigmentation on the dorsal aspect of hand. photo from initial encounter. abstract porphyria cutanea tarda (pct) is characterized by a skin blistering eruption that develops in sun exposed areas of the skin. it is the most common cutaneous porphyria world-wide, and classically associated with hepatic injury but also estrogen use, cigarette smoking, and hiv. in any case of photodistributed persistent blistering skin condition, pct must be high on the differential. this case of a carpenter diagnosed with pct not only illustrates a classic case but also the opportunity to achieve significant response to therapy in a motivated patient particularly with improved access to direct-acting antivirals (daa) for hepatitis c treatment. case presentation skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 57 figure 2. erosions, ulcerations, milia and dyspigmentation on the sun-exposed areas of hands and forearms. photo from initial encounter. punch biopsy showed subepidermal vesicle with hyalinized dermal fibrosis, thickened dermal capillary vessels, and protrusion of dermal papillae into bullous spaces. special stains periodic acid-schiff with diastase (pas-d) and immunohistochemical stain for treponema pallidum were negative for fungal organisms or spirochetes respectively. pasd highlighted the dermal capillary vessel walls. findings were most consistent with pct. given high suspicion of pct with guidance from dermatology this patient had biopsy and the listed lab work completed in one visit in our residency primary care clinic. based on results the patient was then table 1. labs including hep c, hiv and porphyrin studies lab result reference range hep c genotype 1a and viral count 66900 iu/l n/a hiv negative negative iron 88 ug/dl 50-175 ug/dl tibc 399 mcg/dl 250-400 mcg/dl iron saturation 22% 15-50% total porphyrins 32.8 mcg/dl < 1.0 mcg/dl uroprophyrin octa 2493 nmol/l <30 nmol/l heptacarboxylporphyrins 1130 nmol/l <7 nmol/l hexacarboxylaporphyrins 95 nmol/l <20 nmol/l pentacarboxylporphyrins 73 nmol/l <5 nmol/l coproporphyrin, tetra 122 nmol/l <110 nmol/l porphobilinogen 0.3 nmol/l < 1.3 nmol/l figure 3. significant improvement of skin eruption following therapeutic intervention with phlebotomy, hydroxychloroquine, photo protection, alcohol cessation, and curative hepatitis c treatment. referred to gastroenterology for treatment of hepatitis c, to hematology for phlebotomy, and dermatology to help guide therapy with hydroxychloroquine. the patient completed successful treatment of his hepatitis c. he skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 58 was motivated and subsequently discontinued alcohol use, decreased cigarette use, and began practicing proper sun protection. the patient had a significant response to combination therapy with near complete resolution of his skin condition (figure 3) and happily was able to return to work. porphyrias are uncommon metabolic disorders that result from enzyme deficiency and/or defective enzymes along the heme biosynthetic pathway1,4 porphyria cutanea tarda is the most common cutaneous porphyria worldwide. it is caused by acquired (approximately 75%) or hereditary pct (approximately 25%) defect in a liver enzyme uroporphyrinogen decarboxylase (urod).1,5 clinically, pct presents with skin fragility, blisters, erosions, crusting, and milia on sunexposed areas.1,2 mottled hyperand hypopigmentation and hypertrichosis in the periorbital areas are frequently observed.3 differential diagnosis includes: pct vs bullous lupus erythematous vs bullous pemphigoid vs pseudoporphyria vs other porphyrias vs polymorphorphous light eruption vs pemphigus vulgaris vs less likely atypical presentation of secondary syphilis vs bullous tinea. most cases present after the 4th decade of life.2 men are more commonly affected than women, and there is a strong association with hepatitis c, hemochromatosis, hiv, alcohol use, cigarette smoking, and estrogen use.1,2,4 histologically, subepidermal blisters with cell-poor dermal infiltrate, multi-layering of basement membranes, and deposition of hyaline material in and surrounding blood vessels are noted.1,3 as in the case of our patient, if there are concerns for infectious etiologies like secondary syphilis and bullous tinea, then appropriate stains including treponema pallidum as well as pas-d stains should be considered. however, diagnosis is confirmed by characteristic porphyrin profile. elevated levels of uroporphyrin 7-, 6-, 5-, and 4carboxyl porphyrins in urine and plasma and elevated isocoproporphyrin in stool is suggestive of pct.4,5 treatment is multifactorial but always involves photoprotection.1,3 iron load reduction with phlebotomy or chelation therapy is very effective.1,3,5 antimalarial therapy with low dose chloroquine or hydroxychloroquine is therapeutic by forming a porphyrin-antimalarial complex that can be excreted through the kidneys.1, 3 smoking cessation is encouraged, and iron, alcohol, and other hepatic toxins should be avoided.2 in patients with concomitant hepatitis c or hiv infection, treatment should be pursued.2,4,5 the clinical and economic ramifications of pct can be significant. in addition to morbidity from itching and painful lesions, the manifestations of pct can be disfiguring, leading to social stigma, anxiety, and isolation and often loss of livelihood like our patient. delayed diagnosis and/or treatment may further exacerbate the biopsychosocial consequences. this highlights the importance of a thoughtful differential beyond just immune-bullous diseases when evaluating patients who present with blistering disorders. our patient had multiple risk factors consistent with pct and a clear photo distribution of lesions which proved key in shaping the differential. through effective cross disciplinary communication we were able to order the appropriate studies that facilitated both a discussion skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 59 quick diagnosis and treatment plan. in closing, this case illustrates a classic example of pct and is representative of the profound response to therapy that can be achieved by a motivated patient and effective integrated care. conflict of interest disclosures: none funding: none corresponding author: maulik manharlal dhandha, md mdfmr dermatology 6 east chestnut street, ballard center, augusta, me 04330 phone: 207-623-6680 fax 207-623-6609 email maulikdhandha@gmail.com references: 1. puy h, gouya l, deybach jc. porphyrias. lancet. 2010; 375:924-937. 2. jalil s, grady jj, lee c, et al. associations among behavior-related susceptibility factors in porphyria cutanea tarda. clinical gastroenterology hepatology. 2010; 8:297-302. el. 3. sarkany rp. the management of porphyria cutanea tarda. clinical expermental dermatology. 2001; 26:225-232. 4. hall, b.j. & hall, j. c. saunders manual of skin diseases hall, eleventh edition. philadelphia: wolters kluwer health; 2017. pp 5. bissell m, anderson k.e., & bonkovsky, m.d. porphyria. new england journal of medicine. 2017; 377: 862-872. mailto:maulikdhandha@gmail.com skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 567 brief articles indurated and puckered skin on the lateral thighs hiren kolli, bs1,2, ronald moy, md2 1virginia commonwealth university school of medicine, richmond, va 2moy-fincher-chipps facial plastics & surgery, research department, beverly hills, ca chronic graft-versus-host disease (cgvhd) is an immune-mediated reaction and a major complication following allogeneic hematopoietic stem cell transplantation (hsct). cutaneous manifestations are the most common and often the first sign of gvhd. the clinical presentation can vary widely with pruritus, rash, pain, dyspigmentation and fibrotic or sclerodermatous lesions.1 cgvhd can lead to long-term complications such as cosmetic and functional disorders. moreover, persistent cutaneous lesions can also have a significant impact on morbidty and quality of life.2 here we describe a case of a delayed presentation of sclerodermatous cgvhd. a caucasian man in his 60s presented with asymptomatic, bilateral indurated areas on his lateral thighs. he had a past medical history of leukemia, previously treated with full body radiation and bone marrow transplantation more than 20 years ago. a few years ago, the patient first noticed that he had small hard spots about the size of a silver dollar in symmetrical locations on the lateral side of both upper thighs. over the subsequent years, he became concerned that the spots were growing and expanding distally, but remained otherwise asymptomatic. he denied any history of trauma or surgery in the area. physical examination revealed bilateral puckered skin changes and linear depressions which were more prevalent on the right lateral thigh (figure, 1 and 2). a punch biopsy was performed on the right lateral thigh. figure 1. sclerodermatous cgvhd. the right thigh of the patient with puckered skin and linear depressions. histological assessment revealed fascial thickening and extensive dermal sclerosis. there was general loss of the peri-adnexal introduction case presentation skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 568 fat. the pathologist also noted that there was minimal inflammation (figure, 3 and 4). given the clinical context, a diagnosis of sclerodermatous chronic cutaneous graftversus-host disease was made. the patient was notified and expressed concern about the rapidly expanding hardened areas. we discussed the available treatment options including oral corticosteroids and immunosuppressants. the patient decided to observe and notify us if it became worse or symptomatic. figure 2. sclerodermatous cgvhd. the left thigh of the patient with less evident puckering. figure 3. epidermal thinning with pan-dermal sclerosis (h&e, 2x) figure 4. thickened, homogenized collagen bundles (h&e, 20x) cutaneous manifestations are the most common and are often the presenting sign of graft-versus-host disease (gvhd).3 sclerodermatous gvhd is a rare form of chronic gvhd with a prevalence of approximately 3% in patients receiving allogeneic bone marrow transplantation.4 sclerodermatous gvhd may be generalized or localized. shuman et al5 described the generalized disease as following a biphasic course, with a generalized erythematous rash preceding poikiloderma with sclerotic hidebound skin. dermal induration with no previous lichenoid phase was described in those with localized disease. similar to peñas et al6, we believe that sclerodermatous disease occurred independently of a lichenoid phase in this patient. sclerodermatous gvhd has been characterized by cutaneous features such as sclerosis, atrophy, contractures, ulceration, hair loss and nail changes (dystrophy, atrophy and koilonychia).3 sclerotic eruptions can be characterized by discussion skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 569 fibrosis, which may be superficial and localized, resembling lichen sclerosis and morphea, or deep and disseminated, mimicking systemic scleroderma. in a case series of 10 patients, white et al4 described features of dermal nodules, atrophic white plaques, hyperpigmentation and tethered skin with dimpling. however, a feature that was common among all of the patients was indurated plaques. of note, 90% of the patients had plaques on the arms and legs. additional symptoms such as joint limitations and contractures may develop and should be monitored to allow for early intervention. because the sclerodermatous form of chronic gvhd is rare, there is no gold standard for treatment, and little information exists regarding successful treatment. thirty-two patients with sclerodermatous gvhd were treated with retinoids as an adjunct to standard immunosuppressive therapy such as corticosteroids and ciclosporin. etretinate 1 mg/kg daily was added to the treatment regimen. 74% of patients had some clinical improvement, including 2 with near clearance.7 treatment of sclerodermatous gvhd with ultraviolet a1 (340– 400 nm) without psoralen with standard immunosuppression was shown to achieve a complete response in 3 of 5 patients and a partial response in 2 patients.8 however, relapse is common with this therapy and maintenance treatment is needed. in a series of 12 patients with sclerodermatous gvhd alone or with concomitant lichenoid change, all responded favorably to extracorporeal photopheresis. nine of 12 patients achieved a complete response while 3 made a partial response.9 finally, the british society for bone marrow transplantation recommends physiotherapy and massage of potent topical steroids and calcineurin inhibitors to soften the skin.10 sclerodermatous gvhd must be differentiated from other disorders known to be associated with bone marrow transplantation, such as eosinophilic fasciitis (ef). while the initial phases may be indistinguishable from early sclerodermatous skin changes, the irregular, woody peau d’orange texture of ef is distinct from the morphea-like plaques or atrophic and shiny surface seen in those with sclerodermatous gvhd.11 furthermore, sclerodermatous gvhd may be differentiated from morphea based on the absence of early erythematous lesions as well as a yellow-white sclerotic plaque with erythematous borders, or the aptly named “lilac-ring”.12 this case illustrates a rare variant of chronic gvhd with a delayed presentation. little information exists in the literature regarding prognosis and treatment and therefore highlights the need for additional studies in cutaneous gvhd. conflict of interest disclosures: none funding: none corresponding author: hiren kolli, bs 110 w marshall st. #43 richmond, va 23220 phone: 562-659-4171 email: kollih@vcu.edu references: 1. marks c, stadler m, hausermann p, wolff d, et al. german-austrian-swiss consensus conference on clinical practice in chronic graftversus-host disease (gvhd): guidance for supportive therapy of chronic cutaneous and musculoskeletal gvhd. br j dermatol. 2011;165(1):18-29. https://doi.org/10.1111/j.13652133.2011.10360.x. 2. lee sj, kim ht, ho vt, cutler c, et al. quality of life associated with acute and chronic graftversus-host disease. bone marrow transplant. 2006;38(4):305-10. https://doi.org/10.1038/sj.bmt.1705434. conclusion skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 570 3. strong rodrigues k, oliveira-ribeiro c, de abreu fiuza gomes s, knobler r. cutaneous graftversus-host disease: diagnosis and treatment. am j clin dermatol. 2018;19(1):3350. https://doi.org/10.1007/s40257-017-0306-9. 4. white j, creamer d, du vivier aw, pagliuca a, et al. sclerodermatous graft-versus-host disease: clinical spectrum and therapeutic challenges. br j dermatol. 2007;156(5):1032-1038. https://doi.org/10.1111/j.13652133.2007.07827.x. 5. shulman hm, sale ge, lerner kg, barker ea, et al. chronic cutaneous graft-versus-host disease in man. am j pathol. 1978;91(3):545-70. 6. peñas pf, jones-caballero m, aragues m, et al. sclerodermatous graft-vs-host disease. arch dermatol. 2002; 138:924–34. https://doi.org/10.1001/archderm.138.7.924. 7. marcellus dc, altomonte vl, farmer er, horn td, et al. etretinate therapy for refractory sclerodermatous chronic graft-versus-host disease. blood. 1999;93(1):66-70. 8. calzavara pinton p, porta f, izzi t, venturini m, et al. prospects for ultraviolet a1 phototherapy as a treatment for chronic cutaneous graft-versushost disease. haematologica. 2003; 88(10), 1169-1175. 9. greinix ht, volc-platzer b, rabitsch w, gmeinhart b, et al. successful use of extracorporeal photochemotherapy in the treatment of severe acute and chronic graftversus-host disease. blood. 1998;92(9):30983104. 10. dignan fl, scarisbrick jj, cornish j, clark a, et al. organ‐specific management and supportive care in chronic graft‐versus‐host disease. br j haematol. 2012; 158(1), 62-78. 11. chu, g., lin, h., chen, g., & wu, c. eosinophilic fasciitis following allogeneic bone marrow transplantation in a patient with acute myeloid leukaemia. acta dermato-venereologica. 2014; 94(2), 221-222. 12. mertens, j., seyger, s., thurlings, m., radstake, m., & jong, b. morphea and eosinophilic fasciitis: an update. am j clin dermatol. 2017; 18(4): 491-512. acknowledgements: medical writing support was provided by prescott medical communications group (chicago, il) with financial support from ortho dermatologics; ortho dermatologics is a division of bausch health us, llc | presented at winter clinical dermatology conference • january 17-22, 2020 • kohala coast, hi synopsis ◾ psoriasis is a chronic, immune‑mediated disease that can have frequent exacerbations and remissions1 ◾ disease characteristics and optimal treatment strategies for psoriasis may differ between males and females2 ◾ females may have an increased burden of disease compared with males, as they have been shown to have higher levels of stress, stigmatization, and loneliness due to psoriasis3 ◾ recent phase 3 clinical data demonstrated the efficacy and tolerability of a fixed combination lotion containing halobetasol propionate 0.01% and tazarotene 0.045% (hp/taz; duobrii® ortho dermatologics, bridgewater, nj) in patients with moderate‑to‑severe localized plaque psoriasis4,5 objective ◾ to evaluate efficacy and safety of hp/taz lotion in female and male patients with moderate‑to‑severe plaque psoriasis methods ◾ in two phase 3, multicenter, double‑blind studies, participants were randomized (2:1) to receive hp/taz or vehicle lotion once‑daily for 8 weeks, with a 4‑week posttreatment follow‑up4,5 • at baseline, patients were required to have an investigator global assessment (iga) score of 3 or 4 (5‑point scale; 0=clear and 4=severe) and affected body surface area (bsa) of 3% to 12% • in these studies, cerave® hydrating cleanser and cerave® moisturizing lotion (l’oreal, ny) were provided as needed for optimal moisturization/cleaning of the skin ◾ data from these two studies were pooled and analyzed post hoc in female and male participants ◾ efficacy assessments included treatment success (≥2‑grade improvement from baseline in the iga score and score of ‘clear’ or ‘almost clear’ [primary endpoint]), impact on individual signs of psoriasis at the target lesion, and change in bsa affected ◾ treatment‑emergent adverse events (teaes) were evaluated safety and efficacy of a fixed combination halobetasol propionate 0.01%/tazarotene 0.045% (hp/taz) lotion in the treatment of females with moderate‑to‑severe plaque psoriasis linda stein gold, md1; boni elewski, md2; zoe draelos, md3; tina lin, pharmd4 1henry ford hospital, detroit, mi; 2university of alabama at birmingham school of medicine, birmingham, al; 3dermatology consulting services, pllc, high point, nc; 4ortho dermatologics*, bridgewater, nj *ortho dermatologics is a division of bausch health us, llc. results ◾ the analysis population included 146 female participants (hp/taz lotion, n=101; vehicle, n=45) and 272 male participants (hp/taz lotion, n=175; vehicle, n=97) efficacy ◾ at week 8, the percentage of female and male participants with treatment success was significantly greater in the hp/taz group than the vehicle group; significant differences were observed by week 2 and maintained posttreatment (figure 1) ◾ significantly more hp/taz‑treated female and male participants achieved a ≥2‑grade improvement in erythema, plaque elevation, and scaling at week 8 compared with the vehicle group (figure 2) ◾ females and males treated with hp/taz lotion had a significantly greater reduction from baseline in affected bsa at week 8 versus the vehicle group, with significant differences observed as early as week 4 for females and week 2 for males; significant differences were sustained posttreatment for both females and males (figure 3) safety ◾ the most frequently reported treatment‑related teaes in the female hp/taz group were contact dermatitis, pruritis, and application site pain (all 4.0%); pruritis was the most common teae deemed related to vehicle treatment (7.0%) ◾ for males in the hp/taz group, the most frequently reported treatment‑related teae was contact dermatitis (7.6%); in the vehicle group, no teaes deemed related to treatment occurred in >1 male conclusions ◾ halobetasol propionate 0.01% and tazarotene 0.045% lotion was associated with significant reductions in disease severity in female as well as male patients with moderate‑to‑severe psoriasis, with good tolerability and safety over 8 weeks of once‑daily use references 1. nestle fo, et al. n engl j med. 2009;361(5):496‑509. 2. hotard rs, et al. j am acad dermatol. 2000;42(4):620‑623. 3. gottlieb ab, et al. int j womens dermatol. 2019;5(3):141‑150. 4. stein gold l, et al. j am acad dermatol. 2018;79(2):287‑293. 5. sugarman jl, et al. j drugs dermatol. 2018;17(8):855‑861. author disclosures dr. linda stein gold has served as investigator/consultant or speaker for ortho dermatologics, leo, dermavant, incyte, novartis, abbvie, and lilly. dr. boni elewski has provided clinical research support (research funding to university) for abbvie, anaptys‑ bio, boehringer ingelheim, bristol myers squibb, celgene, incyte, leo, lilly, merck, menlo, novartis, pfizer, regeneron, sun, ortho dermatologics, vanda and as a consultant (received honorarium) from boehringer ingelheim, celgene, leo, lilly, menlo, novartis, pfizer, sun, ortho dermatologics, verrica. dr. zoe draelos received funding from ortho dermatologics to conduct the research presented in this poster. dr. tina lin is an employee of ortho dermatologics and may hold stock and/or stock options in its parent company. figure 1. overall treatment successa by study visit in female and male participants (itt population, pooled) a. female participants hp/taz lotion (n=101) vehicle (n=45) treatment posttreatment p e rc e n ta g e o f f e m a le p a rt ic ip a n ts 12.0% 27.8% 37.9% 44.5% 32.8% 0.1% 4.6% 7.0% 9.9% 3.4% 0% 10% 20% 30% 40% 50% 60% 70% 0 2 4 6 8 12 study visit (weeks) b. male participants hp/taz lotion (n=175) vehicle (n=97) 12 treatment posttreatment p e rc e n ta g e o f m a le p a rt ic ip a n ts 8.0% 24.9% 37.5% 38.4% 33.6% 2.1% 5.5% 7.7% 9.8% 11.1% 0% 10% 20% 30% 40% 50% 60% 70% 0 2 4 6 8 study visit (weeks) *p<0.05 vs vehicle, **p<0.01 vs vehicle, ***p<0.001 vs vehicle. atreatment success is defined as a ≥2‑grade improvement from baseline in iga score and a score of ‘clear’ or ‘almost clear’ (0 or 1) hp/taz, halobetasol propionate 0.01% and tazarotene 0.045%; iga, investigator global assessment; itt, intent‑to‑treat. figure 2. treatment successa in psoriasis signs at week 8 in female and male participants (itt population, pooled) a. female participants 65.5% 24.7% 52.9% 63.8% 17.0% 18.9% erythema plaque elevation scaling p e rc e n ta g e o f f e m a le p a rt ic ip a n ts hp/taz lotion (n=101) vehicle (n=45) 0% 10% 20% 30% 40% 50% 60% 70% 80% b. male participants 43.5% 57.2% 58.8% 13.4 % 20.0% 19.1% 0% 10% 20% 30% 40% 50% 60% 70% 80% erythema plaque elevation scaling p e rc e n ta g e o f m a le p a rt ic ip a n ts hp/taz lotion (n=175) vehicle (n=97) ***p<0.001 vs vehicle. a treatment success is defined as a ≥2‑grade improvement from baseline in each individual sign of psoriasis at the target lesion. hp/taz, halobetasol propionate 0.01% and tazarotene 0.045%; itt, intent‑to‑treat. figure 3. mean percent reduction in overall affected body surface area (bsa) by study visit in female and male participants (itt population, pooled) a. female participants hp/taz lotion (n=101) vehicle (n=45) treatment posttreatment p e rc e n t c h a n g e fr o m b a se lin e -7.3% -18.0% -29.7% -34.2% -36.8% -3.1% -3.9% -9.3% -8.7% -2.6% -50% -40% -30% -20% -10% 0% 10% 20% 0 2 4 6 8 12 study visit (weeks) b. male participants hp/taz lotion (n=175) vehicle (n=97) treatment posttreatment p e rc e n t c h a n g e fr o m b a se lin e -8.4% -22.4% -32.6% -39.6% -32.6% 2.3% 1.2% -0.4% 0.7% 5.5% -50% -40% -30% -20% -10% 0% 10% 20% 0 2 4 6 8 12 study visit (weeks) **p<0.01 vs vehicle, ***p≤0.001 vs vehicle. hp/taz, halobetasol propionate 0.01% and tazarotene 0.045%; itt, intent‑to‑treat. skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 288 brief articles erythromelalgia in a patient with mast cell activation syndrome: response to low dose naltrexone anastasia o. kurta, do1, leonard b. weinstock, md, facg2, natalie semchyshyn, md3 1saint louis university, department of dermatology, st. louis, mo 2specialists in gastroenterology, st. louis, mo 3saint louis university, department of dermatology, st. louis, mo erythromelalgia (em) can be disabling and difficult to treat. the incidence is 1.3 per 100,000 people per year.1 diagnostic criteria include: burning pain and erythema of the extremities, pain aggravated by warming/relieved by cooling, and increased skin temperature.2 affected areas usually appear red and edematous and can have associated acrocyanosis, livedo reticularis, facial flushing, cutaneous necrosis and ulceration. the three major forms include: type 1 – associated with thrombocythemia; type 2 – primary, familial, or idiopathic; and type 3 – associated with vascular and autoimmune diseases. familial em has been linked to dominant gain-of-function missense mutations in the scn9a gene, which encodes the voltage-gated sodium channel alpha subunit na(v)1.7, thought to be involved in nociception.3 there is no definitive treatment for em. we present a case of a patient with mast cell activation syndrome (mcas) and em, who had a good response to low dose naltrexone (ldn). a 55-year-old caucasian female presented with an 8-month history of em prior to our evaluation. the patient reported bilateral feet symptoms of burning pain, pricking sensation, and temperature changes ranging from hot to cold. she could not wear shoes without severe pain. treatment with aspirin, nortriptyline, diltiazem, and topical nifedipine failed to provide relief. gabapentin marginally reduced her pain. metoprolol worsened the pain. she had a history of raynaud’s phenomenon since age 15. review of systems revealed a long history of fatigue, eye irritation, mouth sores, chest pain, palpitations, near syncope, bloating, abdominal pain, alternating diarrhea and constipation, heartburn, frequent urination, chronic headaches, muscle pain, anxiety, depression, brain fog, alopecia, and easy bruising. introduction case report erythromelalgia is a rare condition that may be associated with a variety of underlying conditions and is often refractory to therapy. we report a case of a patient with mast cell activation syndrome who developed erythromelalgia and responded to low dose naltrexone. abstract skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 289 physical examination was remarkable for symmetrical erythema and edema of bilateral lower extremities without evidence of temperature difference between the feet and legs (figure 1). figure 1. erythema and edema of right foot. skin punch biopsies of the calf and thigh were performed by her prior clinician to evaluate for small fiber neuropathy in the work up of dysautonomia, and were negative. complete blood count was within normal limits. mast cell mediators (plasma prostaglandin d2, histamine, and heparin; serum tryptase and chromogranin a; and 24-hour urine nmethylhistamine, leukotriene e4, and prostaglandin 11-β-pgf2α) were obtained when she was feeling generally well and were normal. duodenal biopsies revealed 3040 mast cells per high power field. she fulfilled the criteria for mcas by having characteristic symptoms in 2 or more systems and having a mast cell density ≥20 per high power field.4 mast cell-directed therapy was initiated with trials of various histamine 1 and 2 receptor blockers, including ranitidine, famotidine, ketotifen, and loratadine. these medications initially helped reduce her allergic, cardiac, and gastrointestinal symptoms. after 1 month, ldn was added at 1 mg daily and gradually increased to 3 mg daily over 2 months. naltrexone was compounded into capsules by a compounding pharmacy. the histamine blockers were discontinued due to worsening constipation. after two months of ldn therapy, she reported moderate improvement in em symptoms with reduced pain flares in her feet. at a clinic visit, eleven months after initiating ldn, she reported reduced pain, erythema, and edema in her feet (figure 2). she estimated a subjective clinical benefit of 75% that has been maintained with 2 years of ldn therapy. she is able to wear shoes comfortably most of the time, but reported self-limited erythema after exercise walks. she was unable to increase the ldn dose to 4.5 mg due to insomnia but was able to tolerate 3 mg each morning. ldn was continued at 3 mg for 2 years with continued symptom improvement in the extremities (figure 3). ldn also helped reduce bruising, chest pain, and mouth sores. in this case, ldn helped reduce the severity of em in a patient with concomitant mcas. mcas is a chronic multi-system disease of abnormal mast cell activation that leads to inflammatory and allergic illness. mcas has been estimated to have a prevalence of up to 17% (in the german general population); discussion skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 290 figure 2. improvement after 11 months of ldn therapy. figure 3. continued improvement after 2 years of ldn therapy. however, the actual prevalence is not known, as mcas is often not considered in the differential diagnosis of complex patients.4,5 unrecognized and untreated, mcas may account for many refractory and vexing dermatologic symptoms. these include urticaria, pruritis, flushing, hemangiomas, and angioedema. the symptoms of mcas can be numerous and affect multiple organs and systems which further complicates the clinical presentation. ldn has been successfully used off-label as an anti-inflammatory and immunomodulatory agent in several dermatologic conditions.6-8 the ldn dose typically ranges from 1.0 to 4.5 mg daily. the duration of the opioid receptor blockade determines naltrexone’s biotherapeutic response.9 sustained inhibition of mu-opioid receptors by high dose naltrexone has been shown to increase inflammation and proliferation of tumor cells, while intermittent blockade by ldn inhibits cellular proliferation of t and b cells and antagonizes the toll-like receptor 4 (tlr4)mediated pro-inflammatory pathway in macrophages and microglia. increasing evidence suggests that the immune system, specifically the tlr4 pathway, plays an integral role in maintenance of chronic pain.10 mast cells are known to express tlr4 receptors and participate in nociception.11 although the pathophysiology of em is multifactorial and poorly understood, there may be altered inflammatory mediator expression which results from vascular and/or neuronal dysfunction and which may benefit from immune modulators. a search for an underlying cause of presumed idiopathic em should be thoroughly pursued. further studies are necessary to evaluate the therapeutic benefit of ldn in patients with em. skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 291 conflict of interest disclosures: none funding: none corresponding author: anastasia o. kurta, do saint louis university department of dermatology 1755 s. grand blvd st. louis, mo 63104 email: anastasia.kurta@health.slu.edu references: 1. reed kb, davis md. incidence of erythromelalgia: a population-based study in olmsted county, minnesota. j eur acad dermatol venereol. 2009;23:13. doi: 10.1111/j.1468-3083.2008.02938.x. 2. thompson gh, hahn g, rang m. erythromelalgia. clin orthop relat res. 1979;144:249-254. 3. yang y, wang y, li s, et al. mutations in scn9a, encoding a sodium channel alpha subunit, in patients with primary erythermalgia. j med genet. 2004;41:171-174. 4. molderings gj, haenisch b, bogdanow m, et al. familial occurrence of systemic mast cell activation disease. plos one. 2013;8(9):e76241. doi:10.1371/journal.pone.0076241.10. 5. afrin lb, butterfield jh, raithel m, molderings gj. often seen, rarely recognized: mast cell activation disease – a guide to diagnosis and therapeutic options. ann med. 2016;48:190-201. 6. albers ln, arbiser jl, feldman rj. treatment of hailey-hailey disease with low-dose naltrexone. jama dermatol. 2017;153(10):1018-1020. doi: 10.1001/jamadermatol.2017.2446. 7. weinstock lb, myers tl, steinhoff m, smith jp. successful treatment of adult-onset dermatitis herpetiformis with low dose naltrexone. j med case studies. 2017;2(3):27-29. 8. weinstock lb, egeberg a, cottel j, aldridge l. low dose naltrexone therapy for psoriasis: openlabel case series. spin 2019 abstract: p193 9. mclaughlin pj, zagon is. duration of opioid receptor blockade determines biotherapeutic response. biochem pharmacol. 2015;97:236-46. doi: 10.1016/j.bcp.2015.06.016. 10. bruno k, woller sa, miller y, et al. tarteting tolllike receptor-4 (tlr4)-an emerging therapeutic target for persistent pain states. pain. 2018;159:1908-1915. doi: 10.1097/j.pain.0000000000001306. 11. zhang x, wang y, dong h, et al. induction of microglial activation by mediators released from mast cells. cell physiol biochem. 2016;38:15201531. doi: 10.1159/000443093. epub 2016 apr 7. mailto:anastasia.kurta@health.slu.edu acknowledgements: medical writing support was provided by prescott medical communications group (chicago, il) with financial support from ortho dermatologics; ortho dermatologics is a division of bausch health us, llc | 2020 fall clinical dermatology conference® for pas & nps • april 3-5, 2020 • orlando, fl synopsis ◾ topical corticosteroids are the mainstay of psoriasis treatment, particularly for mild disease,1 though topical treatments as part of combination therapy for moderate-to-severe psoriasis is becoming increasingly common ◾ however, continuous use of topicals may be limited due to application-site adverse events (aes)1 ◾ recent phase 3 clinical data have demonstrated efficacy and tolerability of a fixed combination lotion containing halobetasol propionate 0.01% and tazarotene 0.045% (hp/taz; duobrii® ortho dermatologics, bridgewater, nj) in patients with moderate-to-severe localized plaque psoriasis2,3 objective ◾ to investigate aes and local skin reactions following long-term use of hp/taz lotion methods ◾ this was a 1-year multicenter, open-label study (nct02462083) in patients with moderate-to-severe plaque psoriasis ◾ participants were treated with hp/taz lotion once-daily for 8 weeks and intermittently as needed in 4-week intervals (figure 1) • at week 8, treatment was stopped for participants that achieved treatment success; those who did not reach treatment success were treated for 4 additional weeks • all participants were re-evaluated at week 12; those demonstrating ≥1-grade improvement in baseline investigator’s global assessment (iga) continued the study and were subsequently managed in 4-week cycles, either treated with hp/taz lotion once-daily if they had not achieved treatment success or receiving no treatment until the next evaluation if they had achieved treatment success ◾ maximum continuous exposure was 24 weeks figure 1. open-label study design oncedaily hp/taz successa treatment stopped for 4 weeks improvementb continued study and managed in 4-week cycles for up to 1 year, with patients re-evaluated every 4 weeks for treatment successa no improvement discontinued from study no success continued once-daily hp/taz for 4 weeks day 0 week 8 evaluated for treatment successa week 12 evaluated for ≥1-grade improvement from baseline iga week 24 if continuous treatment was received, iga score of 0 or 1 needed to continue study 1 year maximum continuous exposure was 24 weeks. atreatment success defined as score of 0 or 1 on iga. bimprovement defined as ≥1-grade improvement from baseline iga. hp/taz, halobetasol propionate 0.01%/tazarotene 0.045%; iga, investigator’s global assessment. safety and tolerability of fixed combination halobetasol propionate 0.01% and tazarotene 0.045% (hp/taz) lotion in patients with moderate-to-severe plaque psoriasis: results from a 1-year, open-label study figure 2. local skin reactions over time, by severity (safety population) 100% 80% 60% 40% 20% 0% none mild moderate severe p e rc e n ta g e o f p a rt ic ip a n ts baseline week 12 week 24 week 36 week 52 itching baseline week 12 week 24 week 36 week 52 dryness baseline week 12 week 24 week 36 week 52 burning/stinging figure 3. incidence of local skin reactions over time (safety population) 3% 2% 1% 0% p e rc e n ta g e o f p a rt ic ip a n ts 0.5% 1.7% 1.4% 0.9% 0% 1.1% 1.3% 0.8% 0.9% 0.7% 0.2% 0.8% 0.6% 0% 0% 0.4% 1.5% 1.1% 0.4% 0% baseline week 12 week 24 week 36 week 52 skin atrophy baseline week 12 week 24 week 36 week 52 striae baseline week 12 week 24 week 36 week 52 telangiectasias baseline week 12 week 24 week 36 week 52 folliculitis skin reactions ◾ select local signs/symptoms showed marked improvements in severity of itching, dryness, and burning/stinging over the study course; greatest improvement was for itching (figure 2) ◾ incidence of treatment-emergent grade 3 local skin reactions was 22.2% for itching, 6.9% for dryness, and 9.8% for burning/stinging ◾ incidence of other local skin reactions are shown in figure 3 • incidence peaked at 2.3% for skin atrophy (week 8), 2.7% for folliculitis (week 8), and 1.5% for striae and telangiectasias (week 28) ◾ local skin reactions most frequently reported as aes were application site folliculitis (14 participants [2.5%]; 1 discontinued) and application site atrophy (4 participants [0.7%]; 1 discontinued); no participant reported striae or telangiectasias aes ◾ most local skin reactions were transient and resolved prior to end of dosing conclusions ◾ no clinically meaningful trends in local skin reactions were observed following long-term use of a fixed combination hp 0.01%/taz 0.045% lotion ◾ the types of teaes were consistent with those of a corticosteroid and retinoid product, but occurred at lowerthan-anticipated frequencies, suggesting a favorable long-term safety profile for hp/taz lotion references 1. menter a, et al. j am acad dermatol. 2009;60(4):643-659. 2. stein gold l, et al. j am acad dermatol. 2018;79(2):287-293. 3. sugarman jl, et al. j drugs dermatol. 2018;17(8):855-861. author disclosures mark g lebwohl is an employee of mount sinai and receives research funds from abbvie, amgen, arcutis, astrazeneca, boehringer ingelheim, celgene, clinuvel, eli lilly, incyte, janssen research & development llc, kadmon corp llc, leo pharmaceuticals, medimmune, novartis, ortho dermatologics, pfizer, sciderm, ucb inc, and vidac.; is a consultant for allergan, almirall, arcutis inc, avotres therapeutics, birchbiomed inc, boehringer-ingelheim, bristol-myers squibb, cara therapeutics, castle biosciences, corrona, dermavant sciences, foundation for research and education in dermatology, inozyme pharma, leo pharma, meiji seika pharma, menlo, mitsubishi, neuroderm, pfizer, promius/dr. reddy’s laboratories, theravance, and verrica. jeffery sugarman is a consultant for ortho dermatologics, bausch health, regeneron, sanofi, and pfizer. david m pariser has served as consultant to atacama therapeutics, bickel biotechnology, biofrontera ag, celgene, dermira, leo, regeneron, sanofi, tdm surgitech, theravida, and ortho dermatologics; investigator for abbott laboratories, almirall, amgen, aobiome, asana biosciences, bickel biotechnology, celgene, dermavant, dermira, eli lilly, leo, menlo therapeutics, merck & co., novartis, novo nordisk a/s, ortho dermatologics, pfizer, regeneron, and stiefel; on advisory board for pfizer; and on the data monitoring board for bms. jerry bagel is an investigator and speaker for ortho dermatologics. cynthia trickett has served as a speaker for ortho dermatologics. abby jacobson is an employee of ortho dermatologics and may hold stock and/or stock options in its parent company. robert israel is an employee of bausch health us, llc and may hold stock and/or stock options in its parent company. results participants and exposure ◾ a total of 550 participants were included in the safety population • mean age was 51.9 years (range: 19 to 87 years); 65.6% were male and 86.0% were white • baseline iga was moderate (3; 86.5%) or severe (4; 13.5%); median affected body surface area was 5% ◾ median amount of study drug used was 256.5 g, median length of exposure was 172 days, and median number of applications was 164 treatment-emergent adverse events ◾ over half of participants experienced treatment-emergent adverse events (teaes) during the year-long study, primarily during the first 12 weeks (table 1) • most teaes were mild or moderate • none of the serious adverse events (saes) were related to treatment ◾ the most common teaes related to study drug were application site reactions (table 1) table 1. treatment-emergent adverse event summary (safety population) 0-12 weeks (n=527) >12-24 weeks (n=392) >24-36 weeks (n=239) >36 weeks-eos (n=219) total (n=550) number of teaes, no. 395 194 98 71 758 participants with ≥1 teae, n (%) 223 (42.3) 130 (33.2) 61 (25.5) 43 (19.6) 314 (57.1) discontinued study drug due to teae, n (%) 30 (5.7) 9 (2.3) 2 (0.8) 0 41 (7.5) participants with ≥1 sae,a n (%) 6 (1.1) 5 (1.3) 5 (2.1) 2 (0.9) 18 (3.3) treatment-related teae, n (%) 120 (22.8) 43 (11.0) 18 (7.5) 8 (3.7) 161 (29.3) teaes by severity, n (%) mild 99 (18.8) 67 (17.1) 28 (11.7) 22 (10.0) 122 (22.2) moderate 101 (19.2) 55 (14.0) 26 (10.9) 16 (7.3) 151 (27.5) severe 23 (4.4) 8 (2.0) 7 (2.9) 5 (2.3) 41 (7.5) most common treatment-related teaes,b n (%) application site dermatitis 38 (7.2) 20 (5.1) 6 (2.5) 2 (0.9) 56 (10.2) application site pruritus 22 (4.2) 6 (1.5) 4 (1.7) 2 (0.9) 33 (6.0) application site pain 24 (4.6) 2 (0.5) 1 (0.4) 1 (0.5) 28 (5.1) application site irritation 10 (1.9) 4 (1.0) 3 (1.3) 1 (0.5) 13 (2.4) anone of the saes were deemed related to treatment; bin >2% of total participants. eos, end of study; sae, serious adverse event; teae, treatment-emergent adverse event. mark g lebwohl, md1; jeffrey sugarman, md, phd2; david m pariser, md3; jerry bagel, md4; cynthia trickett, pa-c5; abby jacobson, ms, pa-c6; robert israel, md7 1icahn school of medicine at mount sinai, new york, ny; 2university of california, san francisco, ca; 3virginia clinical research center, norfolk, va; 4psoriasis treatment center of central new jersey, east windsor, nj; 5university of texas southwestern, dallas, tx; 6ortho dermatologics*, bridgewater, nj; 7bausch health us, llc*, bridgewater, nj *bausch health us, llc is an affiliate of bausch health companies inc. ortho dermatologics is a division of bausch health us, llc. patients with psoriasis treated with brodalumab: a pooled post hoc analysis of a marker of liver inflammation in individuals with potential indicators of early nonalcoholic fatty liver disease ronald prussick, md1; mark lebwohl, md2; nadege gunn, md3; susan harris, ms4; jason vittitow, phd4; zeev heimanson, pharmd4; abby jacobson, ms, pa-c5; robert j. israel, md4 1george washington university, washington, dc; 2mount sinai hospital, new york, ny; 3austin gastroenterology, austin, tx; 4salix pharmaceuticals, bridgewater, nj; 5ortho dermatologics, bridgewater, nj introduction • nonalcoholic fatty liver disease (nafld) is a broad term that includes a range of liver diseases categorized via imaging or histology in patients with intrahepatic fat accumulation without substantial alcohol consumption (eg, nonalcoholic fatty liver; nonalcoholic steatohepatitis)1 – nafld is intimately linked to metabolic syndrome and is commonly associated with comorbidities, such as diabetes mellitus, dyslipidemia, and obesity1,2 • interestingly, patients with psoriasis are at increased risk for nafld compared with patients without psoriasis3,4 – in one population-based cohort study, patients ≥55 years of age with psoriasis were 70% more likely to have nafld after adjusting for confounding risk factors (adjusted odds ratio, 1.7; 95% confidence interval, 1.2–2.5)4 – published cohort data have suggested that the overall prevalence of nafld in adults with psoriasis approaches 50%5 to 60%6 • although the relationship between psoriasis and nafld has not been fully elucidated, chronic lowgrade systemic inflammation plays a key role in psoriasis and nafld pathophysiologies7,8 • current guidelines from the american association for the study of liver diseases do not recommend routine screening for nafld in high-risk groups in nonhepatology settings1 – therefore, the possible presence of nafld and potential harmful versus beneficial impact of psoriasis medications on the liver in patients with nafld should be carefully considered4 • brodalumab is an anti–interleukin (il)-17 receptor a monoclonal antibody indicated for moderate to severe plaque psoriasis in adults who have failed or lost response on other systemic therapies9 – binding to this receptor inhibits il-17–mediated release of pro-inflammatory cytokines and chemokines • given the potential role chronic low-grade systemic inflammation may play in the relationship between psoriasis and nafld,7,8 a post hoc exploratory analysis was conducted to examine changes in c-reactive protein (crp), a systemic marker of chronic inflammation,10 in patients with psoriasis and early indicators of nafld who were treated with brodalumab objective • post hoc analysis to examine changes in crp levels in patients with psoriasis with an aspartate aminotransferase (ast)-to-alanine aminotransferase (alt) ratio suggestive of liver fibrosis or who had decreases in liver test parameters while taking brodalumab in clinical trials methods • exploratory analysis of data pooled from 4 randomized, double-blind, placebo-controlled trials11-13 • included patients who received ≥1 dose of subcutaneous brodalumab 210 mg every 2 weeks, ustekinumab per the us indicated dosing regimen14 (in 2 trials13), or placebo • patients were subgrouped post hoc (ie, not prespecified outcomes) by various indicators to determine liver disease (eg, baseline ast/alt ratio [≥0.9 suggestive of mild to more advanced fibrosis15,16] and maximum postbaseline ast and alt grade decreases during treatment [based on common terminology criteria for adverse events]) • findings were summarized using descriptive statistics (eg, mean and standard deviation) results • overall, 1496 patients received ≥1 dose of brodalumab 210 mg every 2 weeks, 613 patients received ≥1 dose of ustekinumab, and 879 patients received ≥1 dose of placebo in the 4 trials (table 1) – 802 patients in the brodalumab group, 339 in the ustekinumab group, and 474 in the placebo group had an ast/alt ratio ≥0.9 table 1. demographics and baseline characteristics (overall pooled population) parameter brodalumab 210 mg q2w (n=1496) ustekinumab (n=613) placebo (n=879) age, y, mean (sd) range 45.0 (12.9) 18–75 45.1 (13.1) 18–75 44.6 (12.9) 18–86* male, n (%) 1037 (69.3) 417 (68.0) 607 (69.1) race, white, n (%) 1351 (90.3) 551 (89.9) 799 (90.9) psoriasis duration, y, mean (sd) 18.6 (12.3) 18.5 (12.2) 18.5 (12.0) pasi score, mean (sd) range 20.2 (8.0) 12–72 20.0 (8.4) 12–60 20.0 (8.2) 12–66 *2 patients were >75 years of age. pasi = psoriasis area severity index; q2w = every 2 weeks; sd = standard deviation. • for the subgroup of patients with a baseline ast/alt ratio of ≥0.9 to <1.4, a larger mean numeric decrease from baseline in crp level was observed for patients treated with brodalumab and ustekinumab compared with placebo after 12 weeks of treatment (table 2; figure 1) table 2. crp levels in patients subgrouped by baseline ast/alt ratio assessment brodalumab 210 mg q2w ustekinumab placebo baseline ast/alt ratio of ≥0.9 to <1.4 baseline crp level, mg/l mean (sd) n=607 6.4 (11.8) n=264 4.9 (5.4) n=361 5.7 (9.2) week 12 crp level, mg/l mean (sd) n=599 5.2 (10.9) n=259 4.2 (5.3) n=343 5.3 (12.7) change from baseline at week 12 crp level, mg/l mean (sd) n=587 -1.2 (13.1) n=255 -0.7 (5.4) n=341 -0.3 (11.7) baseline ast/alt ratio ≥1.4 baseline crp level, mg/l mean (sd) n=178 6.6 (12.6) n=69 5.6 (9.8) n=109 6.2 (11.9) week 12 crp level, mg/l mean (sd) n=176 4.6 (9.1) n=64 4.1 (9.6) n=103 6.5 (9.6) change from baseline at week 12 crp level, mg/l mean (sd) n=174 -2.0 (11.6) n=63 -1.7 (7.4) n=102 +0.2 (11.8) alt = alanine aminotransferase; ast = aspartate aminotransferase; crp = c-reactive protein; q2w = every 2 weeks; sd = standard deviation. • similarly, for patients with an ast/alt ratio of ≥1.4, a larger mean numeric decrease from baseline in crp level was observed for patients treated with brodalumab or ustekinumab compared with placebo after 12 weeks of treatment (table 2; figure 1) figure 1. change from baseline in crp levels at week 12, by baseline liver function parameter ast/alt ratio 0.5 0 -0.5 -1 -1.5 -2 -2.5 baseline ast/alt ratio ≥0.9 to <1.4 baseline ast/alt ratio ≥1.4 c h a n g e f ro m b a s e lin e in c r p l e ve l ( m g /l ) brodalumab ustekinumab placebo -1.2 -2.0 -0.7 -1.7 -0.3 0.2 alt = alanine aminotransferase; ast = aspartate aminotransferase; crp = c-reactive protein. • during 12 weeks of treatment, a larger numeric decrease from baseline in crp levels was observed in patients with any decrease in ast grade, alt grade, or both in brodalumab and ustekinumab groups versus placebo (table 3; figure 2) table 3. crp levels in patients with any decrease in ast grade, alt grade, or both during 12 months of treatment assessment brodalumab 210 mg q2w ustekinumab placebo patients with any ast decrease baseline crp level, mg/l mean (sd) n=62 6.7 (8.6) n=20 2.6 (2.3) n=26 6.4 (9.9) week 12 crp level, mg/l mean (sd) n=58 4.1 (5.5) n=19 1.6 (1.9) n=25 7.3 (13.1) change from baseline at week 12 crp level, mg/l mean (sd) n=57 -2.2 (6.0) n=19 -0.8 (2.1) n=25 +1.2 (13.6) patients with any alt decrease baseline crp level, mg/l mean (sd) n=61 6.4 (7.8) n=25 9.3 (34.6) n=30 5.5 (9.6) week 12 crp level, mg/l mean (sd) n=58 4.7 (6.4) n=22 5.0 (15.2) n=31 5.5 (8.6) change from baseline at week 12 crp level, mg/l mean (sd) n=58 -1.6 (6.0) n=22 -5.2 (21.8) n=30 +0.1 (5.6) patients with both ast and alt decrease baseline crp level, mg/l mean (sd) n=23 6.7 (9.0) n=9 2.1 (1.9) n=6 3.4 (3.3) week 12 crp level, mg/l mean (sd) n=22 3.3 (5.0) n=9 1.0 (1.1) n=6 3.1 (3.5) change from baseline at week 12 crp level, mg/l mean (sd) n=22 -3.4 (6.6) n=9 -1.1 (1.5) n=6 -0.4 (2.7) alt = alanine aminotransferase; ast = aspartate aminotransferase crp = c-reactive protein; q2w = every 2 weeks; sd = standard deviation. figure 2. change from baseline in crp levels in patients with decreases in alt and/or ast after 12 weeks of treatment c h a n g e f ro m b a s e lin e in c r p l e ve l ( m g /l ) 2 1 0 -1 -2 -3 -4 -5 -6 any decrease in ast any decrease in alt decrease in ast and alt brodalumab ustekinumab placebo -2.2 -1.6 1.2 -5.2 -3.4 -1.1 -0.4 0.1 -0.8 alt = alanine aminotransferase; ast = aspartate aminotransferase; crp = c-reactive protein. conclusions • the post hoc observation of a decrease in crp levels in patients subgrouped by ast and alt suggests that brodalumab may have activity in reducing liver inflammation and early indicators of nafld; further research is warranted references: 1. chalasani n, younossi z, lavine je, et al. hepatology. 2018;67(1):328-357. 2. lonardo a, ballestri s, marchesini g, angulo p, loria p. dig liver dis. 2015;47(3):181-190. 3. candia r, ruiz a, torres-robles r, et al. j eur acad dermatol venereol. 2015;29(4):656-662. 4. van der voort ea, koehler em, dowlatshahi ea, et al. j am acad dermatol. 2014;70(3):517-524. 5. roberts kk, cochet ae, lamb pb, et al. aliment pharmacol ther. 2015;41(3):293300. 6. miele l, vallone s, cefalo c, et al. j hepatol. 2009;51(4):778-786. 7. prussick rb, miele l. br j dermatol. 2018;179(1):16-29. 8. ganzetti g, campanati a, offidani a. world j hepatol. 2015;7(3):315-326. 9. siliq™ (brodalumab) injection, for subcutaneous use [package insert]. bridgewater, nj: valeant pharmaceuticals; 2017. 10. hadizadeh f, faghihimani e, adibi p. world j gastrointest pathophysiol. 2017;8(2):11-26. 11. papp ka, leonardi c, menter a, et al. n engl j med. 2012;366(13):1181-1189. 12. papp k, menter a, strober b, et al. j am acad dermatol. 2015;72(3):436-439.e1. 13. lebwohl m, strober b, menter a, et al. n engl j med. 2015;373(14):1318-1328. 14. stelara® (ustekinumab) injection, for subcutaneous or intravenous use [package insert]. horsham, pa: janssen biotech, inc.; 2018. 15. sorbi d, boynton j, lindor kd. am j gastroenterol. 1999;94(4):1018-1022. 16. alkhouri n, mccullough aj. gastroenterol hepatol (n y). 2012;8(10):661-668. acknowledgments: the studies were sponsored by amgen/astrazeneca and post hoc analyses were supported by ortho dermatologics. technical editorial and medical writing support were provided under the direction of the authors by mary beth moncrief, phd, synchrony medical communications, llc, west chester, pa. funding for this support was provided by ortho dermatologics. disclosures: rp reports serving on the speakers’ bureau for abbvie inc., celgene corp., janssen pharmaceuticals, inc., and pfizer inc.; serving as a consultant for immunotec inc.; and receiving research funding from celgene corp. and novartis ag. ml reports being an employee of mount sinai, which receives research funds from abbvie inc., bausch health companies inc., boehringer ingelheim gmbh, celgene corp., eli lilly and company, incyte corp., janssen pharmaceuticals, inc./johnson & johnson, leo pharma inc., medimmune, novartis ag, pfizer inc., sciderm gmbh, ucb, inc., and vidac pharma; and serving as a consultant for allergan plc, aqua pharmaceuticals, arcutis pharmaceuticals, boehringer ingelheim gmbh, leo pharma inc., menlo therapeutics, promius pharma, llc, and verrica pharmaceuticals. ng reports serving as a consultant for abbvie inc., dova pharmaceuticals, gilead sciences, inc., intercept pharmaceuticals, inc., and salix pharmaceuticals; and participating in research sponsored by axcella health inc., bristol-myers squibb company, cirius therapeutics, cymabay therapeutics, genfit, gilead sciences, inc., hightide therapeutics inc., luminist, madrigal pharmaceuticals, inc., ngm biopharmaceuticals, inc., novo nordisk, pfizer inc., progenity, inc., and second genome, inc. sh, jv, zh, and rji report being employees of salix pharmaceuticals or its affiliates. aj reports being an employee of ortho dermatologics. 2019 fall clinical dermatology conference (fcdc) • october 17–20, 2019 • las vegas, nv presented at fall clinical dermatology conference 2019 | las vegas, nv, usa | 17–20 october, 2019 previously presented at the 6th congress of the skin inflammation & psoriasis international network background • plaque psoriasis (pso) is an immune-mediated, inflammatory disease; treatment options include systemic medication, phototherapy and biologic agents. • certolizumab pegol (czp) is a unique, fc-free, pegylated, anti-tumor necrosis factor (tnf) biologic approved for the treatment of adults with moderate to severe pso by the fda and ema.1,2 • czp has demonstrated sustained improvements in the skin disease of adults with moderate to severe pso in phase 3 trials.3,4 • in the rapid-psa phase 3 trial of czp in psoriatic arthritis (psa), 54% of patients achieved total resolution of their nail disease after 48 weeks’ czp treatment, increasing to 71% after 4 years.5 however, nail disease outcomes from the czp in pso phase 3 trials have not yet been reported. • here, nail disease outcomes in patients with pso who received double-blinded czp over 48 weeks in three phase 3 trials are presented. methods study design • patients with pso were enrolled in three phase 3, placebo-controlled, double-blind trials of czp in adults with moderate to severe pso: cimpasi-1 (nct02326298), cimpasi-2 (nct02326272) and cimpact (nct02346240) (figure 1).3,4 patients • inclusion criteria: ≥18 years of age with pso for ≥6 months with psoriasis area severity index (pasi) ≥12, ≥10% body surface area affected, physician’s global assessment ≥3 on a 5-point scale. candidates for systemic pso therapy, phototherapy and/or photochemotherapy. • exclusion criteria: previous treatment with czp or >2 biologics; previous treatment with etanercept (etn) (cimpact only); treatment with etn within the first 12-weeks of enrolment (cimpasi-1 and cimpasi-2 only); history of primary failure to any biologic or secondary failure to >1 biologic; erythrodermic, guttate or generalized pso types; current or history of chronic or recurrent viral, bacterial or fungal infections. • presence or absence of concomitant psa (+psa and –psa respectively) was self-reported by patients at baseline. • this analysis includes patients with nail disease at baseline (defined as a modified nail psoriasis severity index [mnapsi] score >0) who received the same dose of czp through 48 weeks. study assessments and statistical analyses • mnapsi 75 (≥75% improvement from baseline), total resolution of nail disease (mnapsi=0) and change from baseline in mnapsi are reported at week 48 (post-baseline mnapsi was not measured prior to week 48). • observed data are reported for patients who received czp 200 mg every two weeks (q2w) and czp 400 mg q2w, stratified by self-reported psa at baseline. • data are pooled for cimpasi-1 and cimpasi-2. references 1. certolizumab pegol prescribing information. available at http:// www.accessdata.fda.gov; 2. certolizumab pegol summary of product characteristics. available at http://www.ema.europa.eu/ema; 3. gottlieb ab. et al. jaad 2018;79:302–14.e6; 4. lebwohl m. et al. jaad 2018;79:266–76.e5; 5. van der heijde d. rmd open 2018;4:e000582. author contributions substantial contributions to study conception/design, or acquisition/ analysis/interpretation of data: abg, dt, cl, yp, sk, mb, kr; drafting of the publication, or revising it critically for important intellectual content: abg, dt, cl, yp, sk, mb, kr; final approval of the publication: abg, dt, cl, yp, sk, mb, kr. author disclosures abg: abbvie, allergan, beiersdorf inc., bristol-myers squibb, celgene, dermira inc., eli lilly, janssen, incyte, leo pharma, novartis, reddy labs, sun pharma, ucb pharma, valeant; dt: abbvie, almirall, amgen, boehringer-ingelheim, celgene, dignity, dr. reddy, galapagos, gsk, janssen, leo pharma, morphosis, msd, eli lilly, novartis, pfizer, sandozhexal, regeneron/sanofi, ucb pharma; cl: abbvie, actavis, amgen, boehringer ingelheim, celgene, coherus, corrona, dermira inc., eli lilly, galderma, glenmark, janssen, leo pharma, merck, novartis, novella, pfizer, sandoz, stiefel, wyeth, ucb pharma, vitae. treasurer of the international psoriasis council. fellow of the american academy of dermatology. member of the american dermatological association. adjunct professor of dermatology at st. louis university school of medicine. private practice in st. louis, mo; yp: abbvie, baxter, boehringer ingelheim, celgene, centocor/janssen, eli lilly, emd serono, gsk, leo pharma, medimmune, merck, novartis, pfizer, regeneron, sanofi genzyme, takeda, ucb pharma; sk, mb: employees of ucb pharma; kr: abbvie, affibody, amgen, biogen, boehringer ingelheim, celgene, centocor, covagen, forward pharma, gsk, janssen-cilag, kyowa kirin, leo pharma, eli lilly, medac, merck sharp & dohme corp., novartis, ocean pharma, pfizer, regeneron, samsung bioepis, sanofi, takeda, ucb pharma, valeant, xenoport. acknowledgements the studies were funded by dermira inc. in collaboration with ucb pharma. ucb is the regulatory sponsor of certolizumab pegol in psoriasis. we thank the patients and their caregivers in addition to the investigators and their teams who contributed to this study. the authors acknowledge bartosz łukowski, msc, ucb pharma, brussels, belgium for publication coordination and hinal tanna, phd, costello medical, cambridge, uk for medical writing and editorial assistance. all costs associated with development of this poster were funded by ucb pharma. since conducting this work kr has moved institute and is now affiliated with skinflammation® center, hamburg, and dermatologikum berlin, berlin, germany. conclusions • substantial proportions of patients with pso treated with czp over 48 weeks showed improved nail disease, with more than 6 in every 10 patients achieving total resolution. • czp demonstrated similar efficacy in treating nail disease in pso patients with and without concomitant psa. • the efficacy of czp treatment on nail disease outcomes observed in patients with pso is comparable with previously reported efficacy in patients with psa. objective • to report the impact of 48 weeks’ certolizumab pegol treatment on nail disease outcomes in patients with moderate to severe plaque psoriasis. nail outcome improvements with certolizumab pegol in moderate to severe plaque psoriasis: results from phase 3 trials a. b. gottlieb,1 d. thaçi,2 c. leonardi,3 y. poulin,4 s. kavanagh,5 m. boehnlein,6 k. reich7 1icahn school of medicine at mount sinai, new york, ny, usa; 2university of lübeck, lübeck, germany; 3central dermatology and saint louis university school of medicine, st louis, mo, usa; 4centre de recherche dermatologique du québec métropolitain, québec, canada; 5ucb pharma, raleigh, nc, usa; 6ucb pharma, monheim, germany; 7sciderm research institute, hamburg, and dermatologikum berlin, germany figure 1. study design for czp in pso phase 3 trials results • 154 patients in cimpasi-1/2 and 71 patients in cimpact had nail disease at baseline and were randomized to czp treatment at week 0. • patient baseline characteristics are shown in table 1. • patients completing 48 weeks of czp treatment in cimpasi-1/2 or cimpact demonstrated considerable improvement in their nail disease (figure 2a), and of these: – over 70% patients achieved mnapsi 75 (figure 2b) – over 65% demonstrated total resolution of their nail disease (figure 2c). • similar results were observed between patients with and without self-reported concomitant psa (figure 2). only patients who received the same dose of czp through weeks 0–48 are included in these analyses. apatients received czp 400 mg loading dose at weeks 0, 2 and 4 or weeks 16, 18 and 20. bw: bi-weekly; czp: certolizumab pegol; etn: etanercept; ld: loading dose; pasi: psoriasis area severity index; q2w: every two weeks; q4w: every four weeks. table 1. demographics and baseline characteristics of czp-treated patients with nail disease in cimpasi-1/cimpasi-2 and cimpact data are reported for patients with nail disease at baseline (mnapsi >0) treated with czp (dose combined: czp 400 mg or 200 mg q2w following a 400 mg loading dose at weeks 0, 2, 4) through 48 weeks. bmi: body mass index; bsa: body surface area; czp: certolizumab pegol; il: interleukin; mnapsi: modified nail psoriasis severity index; pasi: psoriasis area severity index; pga: physician's global assessment; psa: psoriatic arthritis; +psa/−psa: patients with pso with/without self-reported psa; pso; plaque psoriasis; q2w: every two weeks; sd: standard deviation; tnf: tumor necrosis factor. all pso patients pso patients +psa pso patients −psa cimpasi-1/2 (n=154) cimpact (n=71) cimpasi-1/2 (n=37) cimpact (n=12) cimpasi-1/2 (n=117) cimpact (n=59) age, years, mean ± sd 45.9 ± 13.0 43.2 ± 12.4 48.1 ± 13.1 44.9 ± 13.9 45.2 ± 13.0 42.8 ± 12.1 male, n (%) 112 (72.7) 47 (66.2) 23 (62.2) 6 (50.0) 89 (76.1) 41 (69.5) bmi, kg/m2, mean ± sd 30.6 ± 6.5 28.3 ± 5.0 31.9 ± 7.1 28.0 ± 6.5 30.2 ± 6.2 28.3 ± 4.8 prior biologic use, n (%) 61 (39.6) 18 (25.4) 16 (43.2) 6 (50.0) 45 (38.5) 12 (20.3) anti-tnf 39 (25.3) 0 (0.0) 12 (32.4) 0 (0.0) 27 (23.1) 0 (0.0) anti-il-17 11 (7.1) 14 (19.7) 3 (8.1) 6 (50.0) 8 (6.8) 8 (13.6) anti-il-12/il-23 8 (5.2) 2 (2.8) 1 (2.7) 0 (0.0) 7 (6.0) 2 (3.4) pso duration, years, mean ± sd 19.3 ± 12.9 19.1 ± 11.0 20.2 ± 14.1 23.8 ± 15.1 19.0 ± 12.6 18.2 ± 9.9 pasi, mean ± sd 19.8 ± 8.1 21.0 ± 7.5 19.4 ± 9.9 17.9 ± 5.6 19.9 ± 7.5 21.6 ± 7.8 bsa affected, %, mean ±sd 24.2 ± 14.3 28.0 ± 16.8 22.7 ± 14.7 22.6 ± 12.2 24.6 ± 14.2 29.1 ± 17.5 pga, n (%)             3 (moderate) 112 (72.7) 50 (70.4) 27 (73.0) 11 (91.7) 85 (72.6) 39 (66.1) 4 (severe) 42 (27.3) 21 (29.6) 10 (27.0) 1 (8.3) 32 (27.4) 20 (33.9) mnapsi, mean ± sd 5.2 ± 3.0 4.6 ± 2.7 5.9 ± 3.1 5.7 ± 2.3 5.0 ± 2.9 4.4 ± 2.8 a) cimpasi-1 and cimpasi-2 b) cimpact figure 2. week 48 nail disease outcomes in pso patients with and without psa treated with czp in cimpasi-1/cimpasi-2 and cimpact observed case data are reported for all patients with pso who had nail disease at baseline (mnapsi >0) treated with czp (dose combined: czp 400 mg or 200 mg q2w following a 400 mg loading dose at weeks 0, 2, 4) through 48 weeks in cimpasi-1/2 and cimpact, and for the subpopulations of patients with and without self-reported psa (+psa/−psa). czp: certolizumab pegol; mnapsi: modified nail psoriasis severity index; mnapsi 75: ≥75% improvement in mnapsi; psa: psoriatic arthritis; pso; plaque psoriasis. 0 48 re-randomization 16 4032week initial treatment period (double-blinded) maintenance period (double-blinded) <pasi 75 <pasi 50 – open-label treatment <pasi 75 <pasi 75 <pasi 75 placebo q2w czp 400 mg q4wetn 50 mg bw washout lda czp 200 mg q2w czp 400 mg q2w czp 400 mg q2w czp 200 mg q2w placebo q2w <pasi 75 entered escape arm (czp 400 mg q2w) 1:3:3:3 randomization 12 lda initial treatment period (double-blinded) maintenance period (double-blinded) <pasi 50 entered escape arm (czp 400 mg q2w) 0week 1:2:2 randomization 4832 40 czp 400 mg q2w 16 czp 200 mg q2wlda <pasi 50 – withdrawn <pasi 50 – withdrawn <pasi 50 – withdrawn pasi 50–74 received lda then czp 200 mg q2w placebo q2w 12 cimpasi-1/2 cimpact -1.0 -2.0 -3.0 -4.0 0.0 -6.0 c h a n g e f ro m b a se lin e all patients -4.4 n=133 -4.4 n=133 -4.1 n=64 -4.1 n=64 +psa -5.0 n=29 -5.3 n=10 -5.3 n=10 –psa -4.2 n=104 -4.2 n=104 -3.9 n=54 -3.9 n=54-5.0 90 80 70 60 50 40 30 10 20 100 0 r e sp o n d e r ra te ( % ) all patients 72.9% n=133 82.8% n=64 82.8% n=64 +psa 75.9% n=29 90.0% n=10 90.0% n=10 –psa 72.1% n=104 72.1% n=104 81.5% n=54 81.5% n=54 90 80 70 60 50 40 30 10 20 100 0 r e sp o n d e r ra te ( % ) all patients 66.2% n=133 70.3% n=64 70.3% n=64 +psa 69.0% n=29 80.0% n=10 80.0% n=10 –psa 65.4% n=104 65.4% n=104 68.5% n=54 68.5% n=54 a) mnapsi change from baseline b) mnapsi 75 response c) total resolution (mnapsi=0) evaluation of a novel inorganic tinted sunscreen enriched with five antioxidants for protection against uva1 and vl induced hyperpigmentation and erythema omid yousefian, lisa aeschliman, susan mortillo and eduardo ruvolo beiersdorf inc., florham park, nj usa visible light (vl, 400-700 nm) and long wavelength uva1 (vl+uva1, 370-700 nm) have been reported to cause erythema in light skin phototypes, fitzpatrick skin types i-iii (fst i-iii), and to exacerbate pigmentary dermatologic conditions (e.g., melasma, hyperpigmentation, post-inflammatory hyperpigmentation) in individuals with dark skin phototypes (fst iv-vi). until recently, there remained limited options for photoprotection against vl+uva1, including tinted (containing iron oxide [fe2o3]), pigmentary titanium dioxide (tio2), organic-based (chemical) filters, or utilization of a five antioxidant (5 aox) enriched formulation. zinc oxide (zno) and tio2 are often utilized in the development of mineral-based (inorganic) sunscreens as the active ingredients to protect against broadspectrum ultraviolet (uv) radiation via their absorption properties. however, some of these products often leave a white cast, particularly on dark skin, making these products unfavorable, altering skin tone appearance, leading to concerns for sunscreen compliance. the addition of tint (fe2o3) to mineral-based sunscreens aims to improve the cosmetic elegance, blendability into multiple skin tones, and overall compliance for daily sunscreen use. this study aims to evaluate the photoprotection properties of a novel zno-based inorganic tinted sunscreen enriched with five antioxidants (5 aox) against vl+uva1 induced biologic effects (hyperpigmentation and erythema). ten healthy adult subjects with fst iv-vi were enrolled and the effectiveness of the new zno/fe2o3/5 aox sunscreen, compared to several commercially available tinted and non-tinted mineral sunscreens was evaluated. the erythema and pigmentation assessment was performed by diffuse reflectance spectroscopy (drs), polarized photography, and investigator global scoring immediately, 24 hours, and 7 days after irradiation (320 j/cm2). drs results demonstrated that the novel zno/ fe2o3/5 aox can effectively reduce immediate erythema and pigmentation as well as delay pigmentation when compared with formulas containing zno only (p≤0.05). not all inorganic/fe2o3 formulas could significantly reduce erythema and pigmentation induced by uva1/vl when compared with zno-only formula. these results highlight the enhanced effects of 5 aoxenriched tinted mineral sunscreen to be photoprotective against vl+uva1, with a blendable tint designed for use on skin of all color, aimed at improving patient compliance and overall sunscreen use. references: 1. ruvolo e, boothby-shoemaker w, kumar n, et al. int j cosmet sci. 2022;44(3):394-402. 2. lim hw, kohli i, ruvolo e, et al. j am acad dermatol. 2022;86(3s):s27-s37. 3. taylor sc, alexis af, armstrong aw, et al. j am acad dermatol. 2022;86(3s):s9-s17. 4. rigel ds, lim hw, draelos zd, et al. j am acad dermatol. 2022;86(3s):s18-s26. 5. kohli i, chaowattanapanit s, mohammad tf, et al. br j dermatol. 2018;178(5):1173-1180. 6. mahmoud bh, ruvolo e, hexsel cl, et al. j invest dermatol. 2010;130(8):2092-2097. 7. randhawa m, seo i, liebel f, et al. plos one. 2015;10(6):e0130949. 8. mann t, eggers k, rippke f, et al. photodermatol photoimmunol photomed. 2020;36(2):135-144. 9. kollias n, baqer a. photochem photobiol. 1984;39(5):651-659. 10. liebel f, kaur s, ruvolo e, et al. j invest dermatol. 2012;132(7):1901-1907. • vl+uva1 has been reported to cause erythema in light skin phototypes (fst i-iii) and hyperpigmentation in dark skin phototypes (fst iv-vi) • zinc oxide (zno) and titanium dioxide (tio2) are often utilized in the development of mineral-based (inorganic) sunscreens as the active ingredients to protect against broad-spectrum ultraviolet (uv) radiation via their absorption properties. however, some of these products often leave a white cast, particularly on dark skin, making these products unfavorable, altering skin tone appearance, leading to concerns for sunscreen compliance • this study demonstrates the photoprotective efficacy of a novel znobased inorganic tinted sunscreen enriched with five antioxidants (5 aox) against vl+uva1 induced biologic effects (hyperpigmentation and erythema) • drs results demonstrated that the novel zno/fe2o3/5 aox can effectively reduce immediate erythema and pigmentation as well as delay pigmentation when compared with formulas containing zno only (p≤0.05) • these results highlight the enhanced effects of 5 aox-enriched tinted mineral sunscreen to be photoprotective against vl+uva1, with a blendable tint designed for use on skin of all color aimed at improving patient compliance and overall sunscreen use abstract summary and conclusions results materials and methods study participants: ten (10) subjects with fst iv-vi were enrolled. the study was approved by sterling investigational review board and conducted at dermico laboratory, broomall, pa. written informed consent was obtained from all subjects. vl+uva1 phototesting: a single vl+uva1 dose of 320 j/cm2 was administered with a modified solar simulator. solar light ls1000 (solar light company inc, glenside, pa), with xenon arc light and customized filters. filtered spectral output consisted of 1.4% uva1 (340-400 nm), 96.3% vl (400-700 nm) and 2.28% ir (700-1800 nm). spectroradiometric assessment of the long uva/vl sources was performed with a calibrated spectroradiometer ol-754 (gooch and housego, orlando, fl). product application and vl/uva1 exposure on visit 1 (day 0), subjects were marked with sites on their mid-lower back. on one (1) of the sites product c was applied at 2 mg/cm2 in a randomized fashion, and allowed to dry for 20 minutes. on visit 2 (day 1), product c was reapplied at 2 mg/cm2 to the same site and allowed to dry for 20 minutes. on visit 3 (day 2) product c was reapplied at 2 mg/ cm2 to the same site and allowed to dry for 20 minutes. on visit 4 (day 3) product c was reapplied at 2 mg/cm2 to the same site. products a, e, f, g, h and i were applied to other marked sites at 2 mg/cm2 and all products were allowed to dry for 20 minutes following which all treated sites and an untreated site u were irradiated with a vl+uva1 dose of 320 j/cm2 at an irradiance of 95 mw/cm2 (~ 1 hour). site u served as positive control because it was untreated but irradiated. assessments assessments were done by digital cross-polarized photography, investigator global assessment (iga) score for pigmentation, and diffuse reflectance spectroscopy (drs). all assessments were performed for all sites immediately, 24 hours and 7 days after vl+uva1 exposure. for drs, the instrument consisted of a quartz halogen light source (ocean optics, boca raton, fl), a bifurcated fiber bundle (multimode fiber optics, east hanover, nj), a bwtek glacier spectrometer (b&w tek, plainsboro, nj), and a laptop. one leg of the fiber bundle was connected to the light source and the other to the spectrometer. measurements were performed by placing the common end of the fiber bundle gently against the skin without perturbing blood flow. a reflectance spectrum was acquired in the range of 400-820 nm. five (5) measurements were collected from each site at all time points after vl+uva1 exposure. measurements from normal untreated and non-irradiated skin were also collected for normalization. apparent concentrations of hemoglobin and melanin, and area under the curve from 400-700 nm (auc, relative dyschromia) were calculated from the drs data. data analysis primary data analysis was to compare the pooled data from all time points as well as drs results between 24.08% zinc oxide control and each treated pooled data set using fisher lsd method with 95% confidence. significance was determined for each paired data set with a p-value less than or equal to 0.05. all analyses were done using originpro software (originlab corporation, northampton, ma). figure 1. representative cross-polarized photographs of control and treated site of a subject’s back at various time points. ten healthy adult subjects with fst iv-vi were enrolled and the effectiveness of the novel zno/fe2o3/5 aox sunscreen, compared to several commercially available tinted and non-tinted mineral sunscreens was evaluated. the erythema and pigmentation assessment was performed by diffuse reflectance spectroscopy (drs), polarized photography, and investigator global scoring immediately, 24 hours, and 7 days after irradiation (320 j/cm2). figure 2. drs measured change a) in melanin content (all time points, pooled) and b) in oxy-hemoglobin (delta oxy-hb, all time points, pooled) for all sites after vl+uva1 irradiation. *represents statistically significant difference (p≤0.05) compared to indicated products. a. 24.08% zinc oxide control spf 50; c. 24.08% zinc oxide + 5 aox + iron oxides spf 35; e. 5.5% tio2 + 10% zinc oxide + iron oxides spf 30; f. 2% tio2 + 15% zinc oxide + iron oxides spf 40; g. 9% zinc oxide + 7.5% octinoxate + iron oxides spf 46; h. 11% tio2 + iron oxides spf 50; i. 21.6% zinc oxide spf 50. *represents statistically significant difference (p < 0.05) compared to indicated products. hyperpigmentation (melanin): all time points, pooled data erythema (oxy-hemoglobin): all time points, pooled data 0 0.05 0.1 0.15 0.2 0.25 a i g f e h c d iff er en ce m el an in (e xp os ed -n on -e xp os ed ) 0 0.02 0.04 0.06 0.08 0.1 0.12 0.14 0.16 0.18 0.2 a f e g i c h d iff er en ce o xy -h em og lo bi n (e xp os ed -n on -e xp os ed ) * * * clinical efficacy: erythema and pigmentation (all time points, pooled) statistically significant reduction in melanin and oxy-hemoglobin in novel zno/fe2o3/5 aox, group c (all time points, pooled data) 2023 winter clinical conference – hawaii sponsorship: research sponsored by beiersdorf inc., stamford, ct formula information a 24.08% zinc oxide control spf 50 c 24.08% zinc oxide + 5 aox + iron oxides spf 35 e 5.5% tio2 + 10% zinc oxide + iron oxides spf 30 f 2% tio2 + 15% zinc oxide + iron oxides spf 40 g 9% zinc oxide + 7.5% octinoxate + iron oxides spf 46 h 11% tio2 + iron oxides spf 50 i 21.6% zinc oxide spf 50 a immediate 24 hours 7 days c e f g h i clinical effi cacy: pigmentation (cross-polarized photographs) a 24.08% zinc oxide control spf 50 c 24.08% zinc oxide + 5 aox + iron oxides spf 35 e 5.5% tio2 + 10% zinc oxide + iron oxides spf 30 f 2% tio2 + 15% zinc oxide + iron oxides spf 40 g 9% zinc oxide + 7.5% octinoxate + iron oxides spf 46 h 11% tio2 + iron oxides spf 50 i 21.6% zinc oxide spf 50 formula information the novel zno/fe2o3/5 aox (group c) can effectively reduce pigmentation compared to zinc oxide only formulation (group a) table 1. products tested powerpoint presentation once-daily oral sarecycline 1.5 mg/kg/day is effective for moderate to severe acne vulgaris: results from two 12-week, phase 3, randomized, double-blind clinical trials angela moore, md; lawrence green, md2, suzanne bruce, md; neil sadick, md; eduardo tschen, md, mba; philip werschler, md, faad, faacs; sunil dhawan, md; douglas forsha, md; michael gold, md, faad; scott guenthner, md; steve kempers, md; leon kircik, md; jennifer parish, md; marta rendon, md; phoebe rich, md; linda stein-gold, md; stephen tyring, md, phd; robert weiss, md, faad; adnan nasir, md; carsten schmitz, md, phd; terry boodhoo, ms; alexandre kaoukhov, md; david berk, md; fran cook-bolden, md; ayman grada, md, ms email: ayman.grada@almirall.com introduction  oral broad-spectrum tetracycline-class antibiotics are prescribed for the treatment of moderate to severe inflammatory acne  poor tolerability and bacterial resistance concerns may limit the use of broad-spectrum tetracycline antibiotics for the treatment of acne conclusions sarecycline, a narrow-spectrum tetracycline class antibiotic recently fda-approved for the treatment of moderate to severe acne in ages 9 and older, was safe, well tolerated, and statistically significant at 12 weeks in achieving iga success (defined as ≥2-grade improvement and score 0 [clear] or 1 [almost clear]) and reduction in inflammatory lesion count. design & methodology male and female aged 9 to 45 years between 33 kg and 136 kg results financial support: this study was funded and sponsored by allergan. sarecycline is owned and marketed by almirall, llc. ussey0277 sc1401 sc1402 outcome measure sarecyclinen =483 placebo n = 485 p sarecycline n = 519 placebo n = 515 p iga success* 21.9% 10.5% .0001 22.6% 15.3% .0038 mean percent reduction in inflammatory lesions 52.2% 35.2% .0001 50.8% 36.4% .0001 *note: iga success defined as ≥2-grade improvement and score 0 [clear] or 1 [almost clear] table 1. iga success and inflammatory lesion efficacy at week 12  to evaluate the efficacy and safety of sarecycline, a once-daily, narrow-spectrum tetracycline-class drug in moderate to severe acne objective moderate to severe (iga ≥ 3) facial acne 20 – 50 inflammatory lesions ≤ 100 noninflammatory lesions ≤ 2 nodules  two phase 3 multicentre, randomized, double-blind, placebo-controlled, parallel group studies.  up to 35 day screening period to establish eligibility and baseline  12 week double-blind treatment with study visits at 3, 6, 9, and 12 weeks subjects randomized 1:1 to sarecycline 1.5 mg/kg/day oral or placebo in sc1401 and sc1402 (table 1) iga success rates were 21.9% and 22.6% (sarecycline) versus 10.5% and 15.3% (placebo; p < .0001 and p = .0038). onset of efficacy in inflammatory lesion reduction occurred as early as week 3, with mean percentage reduction in inflammatory lesions at week 12 in sc1401 and sc1402 of 52.5% and 50.8% (sarecycline) versus 35.2% and 36.4% (placebo) (figs 1 & 2). efficacy on truncal acne in (fig 3) adverse events ≥ 2% in any group are shown in table 2.  co-primary efficacy endpoints:  absolute change in facial inflammatory lesion count at week 12  iga success – iga score of 0 (clear) or 1 (almost clear) and ≥ 2 point improvement from baseline  secondary endpoints included absolute and percent change from baseline in inflammatory lesions at weeks 3, 6, & 9. table 2. adverse events ≥ 2% in any group sc1401 sc1402 teaes sarecycline n =483 placebo n = 485 teaes sarecycline n = 519 placebo n = 515 nausea nasopharyngitis headache vomiting 3.1% 3.1% 2.7% 2.1% 2% 2.9% 2.7% 1.4% nasopharyngitis headache 2.5% 2.9% 2.9% 2.4% baseline week 3 week 12 baseline week 3 week 12 vestibular, phototoxic, vulvovaginal candidiasis, and mycotic infections ≤1.1% in sarecycline treated patients. gastrointestinal teae rates were low reference: moore a, green lj, bruce s, sadick n, tschen e, werschler p, cook-bolden fe, dhawan ss, forsha d, gold mh, guenthner s. once-daily oral sarecycline 1.5 mg/kg/day is effective for moderate to severe acne vulgaris: results from two identically designed, phase 3, randomized, double-blind clinical trials. journal of drugs in dermatology: jdd. 2018 sep;17(9):987-96. fig 1 & 2. mean % reduction in facial inflammatory lesions fig 3. truncal acne: % of patients with iga success at wk 12 slide number 1 lilly immunology study was sponsored by eli lilly and company, under license from incyte corporationwinter clinical dermatology conference; hawaii, usa; january 13-18, 2023 methods disclosures ■ m. m. senna has served on advisory boards and/or has been a consultant for: arena pharmaceuticals, concert pharmaceuticals, eli lilly and company, and pfizer; and is a clinical trial investigator for: concert pharmaceuticals and eli lilly and company; o. kwon has been a consultant for: eli lilly and company; and has received clinical study funds from: addpharma, eli lilly and company, and pfizer; b. m. piraccini has received honoraria from or been a consultant for: almirall, eli lilly and company, isdin, pfizer, and vichy laboratoires; r. sinclair has been an investigator for and/or provided professional services to: abbvie, aerotek scientific, akeso biopharma, amgen, arcutis, arena pharmaceuticals, ascend laboratories, astrazeneca, bayer pharmaceuticals, boehringer ingelheim, bristol myers squibb, celgene, coherus biosciences, connect biopharma, cutanea, dermira, eli lilly and company, galderma, glaxosmithkline, janssen, leo pharma, medimmune, merck sharp & dohme, novartis, oncobiologics, pfizer, regeneron, reistone biopharma, roche, samson medical technologies, sanofi, sun pharma, and ucb pharma; s. ball, y. ding, y.-f. chen, and y. dutronc are employees and shareholders of: eli lilly and company; b. king has served on advisory boards and/or is a consultant and/or clinical trial investigator for: abbvie, almirall, altrubio, anaptysbio, arena pharmaceuticals, bioniz therapeutics, bristol myers squibb, concert pharmaceuticals, eli lilly and company, horizon therapeutics, incyte corporation, leo pharma, otsuka/visterra, pfizer, regeneron, sanofi genzyme, twi biotechnology, and viela bio; and is on speaker bureaus for: abbvie, incyte corporation, leo pharma, pfizer, regeneron, and sanofi genzyme ■ medical writing assistance was provided by loredana spoerri, phd, of proscribe – envision pharma group, and was funded by eli lilly and company. this study was previously presented at the european academy of dermatology and venereology 31st congress 2022 eyebrows and eyelashes regrowth across different salt response thresholds in patients with alopecia areata: outcomes from the brave aa clinical program maryanne m. senna,1,2 ohsang kwon,3 bianca maria piraccini,4 rodney sinclair,5 susan ball,6 yuxin ding,6 yun-fei chen,6 yves dutronc,6 brett king7 1lahey dermatology, burlington, usa; 2harvard medical school, boston, usa; 3department of dermatology, seoul national university college of medicine, seoul, republic of korea; 4division of dermatology, department of specialized, diagnostic, and experimental medicine, university of bologna, bologna, italy; 5sinclair dermatology, melbourne, australia; 6eli lilly and company, indianapolis, usa; 7yale school of medicine, new haven, usa background ■ alopecia areata (aa) is a clinically heterogenous, immune-mediated, non-scarring hair loss disorder that varies widely in the amount and pattern of hair loss1 ■ although the scalp is most often affected, aa can develop on any hair-bearing site, including the eyebrows and eyelashes ■ efficacy of baricitinib, an oral selective janus kinase (jak)1/jak2 inhibitor, in the treatment of adult patients with severe aa (defined as severity of alopecia tool [salt] score ≥50) was demonstrated in the phase 2/3 trial, brave-aa1, and the phase 3 trial, brave-aa2, 2 randomized, double-blinded, placebo-controlled trials2,3 – the primary endpoint was the proportion of patients who achieved salt score ≤20 at week 36 – key secondary endpoints included the proportion of patients with no or minimal gaps on eyebrows and eyelashes at week 36 ■ however, the clinical response for the scalp, eyebrows, and eyelashes may vary between patients and over time objective ■ to evaluate whether patients with aa treated with baricitinib who had not achieved salt score ≤20 at week 52 achieved clinically meaningful improvements in eyebrow or eyelash loss conclusions ■ the data show an impact of baseline severity and duration of hair loss (disease and current episode) on salt score response rates for scalp, eyebrow, and eyelash hair loss ■ not surprisingly, the highest response rates for eyebrow and eyelash regrowth were observed in patients who had also experienced scalp hair regrowth ■ however, about half of the patients with partial scalp response and 15-20% of those with no scalp response experienced meaningful improvement in eyebrow and eyelash regrowth with baricitinib 4-mg, which has been identified as a highly important treatment goal for patients ■ further analyses may be required to clarify if these observations represent different patterns of clinical responses or are linked to different kinetics of hair regrowth between the scalp, eyebrows, and eyelashes ■ longer studies may be required to observe complete benefit abbreviations aa=alopecia areata; bari=baricitinib; bmi=body mass index; ci=confidence interval; clinro=clinician-reported outcome; clinro eb=clinro measure for eyebrow hair loss; clinro el=clinro measure for eyelash hair loss; covid-19=coronavirus disease 2019; pbo=placebo; qd=once daily; salt=severity of alopecia tool; salt30=≥30% improvement from baseline in total salt score; w=week study design,a brave-aa1 and brave-aa2 key results scan or click the qr code or use this url (https://lillyscience.lilly.com/congress/wcdc2023) for a list of all lilly content presented at the congress. other company and product names are trademarks of their respective owners. references 1. pratt c, et al. nat rev dis primers. 2017;3:17011 2. king b, et al. j am acad dermatol. 2021;85:847-853 3. king b, et al. n engl j med. 2022;386:1687-1699. 4. olsen ea, et al. j am acad dermatol. 2004;51:440-447. 5. wyrwich kw, et al. am j clin dermatol. 2020;21;725-732 at week 52, achievement of meaningful improvement in eyebrow and eyelash regrowth was observed across all response subgroups, with greater response rates in the salt score ≤20 response subgroup a figure is not the full study design, but only the first year of both trials; b patients randomized to bari (4-mg or 2-mg qd) at baseline retained their treatment allocation through week 52, whereas pbo non-responders were rescued at week 36; c long-term extension period lasts until week 104. eligible patients may remain in the trials until week 200 clinro measures for eyebrow and eyelash hair losstm,5 statistical analyses results data are mean (standard deviation) unless stated otherwise a patients who achieved salt score ≤20 (no more than 20% scalp hair loss) at week 52; b patients who failed to reach salt score ≤20 but achieved salt30 at ≥1 post-baseline visit; c patients who never achieved salt score ≤20 or salt30 by week 52; d n=96 for race; e n=153 demographics and patient characteristics by salt score response subgroup ■ this analysis included weeks 0-52 of both studies ■ the analysis included only patients enrolled in the active treatment arms (baricitinib 4-mg and baricitinib 2-mg; patients in the placebo arm were not included) key eligibility criteria, brave-aa1 and brave-aa2 ■ male (≥18 to ≤60 years old) or female (≥18 to ≤70 years old) ■ hair loss involving ≥50% of the scalp, assessed with salt ■ current episode of aa >6 months to <8 yearsa ■ no spontaneous improvement in the 6 months before screening ■ not primarily a “diffuse” type of aa ■ no concomitant treatments for aa allowedb a patients who had aa for ≥8 years could be enrolled if episodes of regrowth (spontaneous or due to under-treatment) had been observed on the affected areas over the past 8 years b oral/topical minoxidil or finasteride was allowed if on stable dose for 12 months, and bimatoprost ophthalmic solution was allowed if on stable dose for 8 weeks salt score4 ■ the salt score is a weighted sum of the percent of hair loss in the 4 quadrants of the scalp (top, back, left side, and right side), ranging from 0 (no scalp hair loss) to 100 (complete scalp hair loss) ■ salt score interpretation – salt score 0=no hair loss – salt score 100=complete hair loss – salt score ≤20=20% or less scalp hair loss (80% scalp coverage) ■ salt scores with subscripts refer to percent improvement from baseline (eg, salt30=≥30% improvement from baseline in total salt score) response subgroups ■ baricitinib 4-mg and 2-mg subgroups were defined by the degree of scalp hair regrowth (salt score) at week 52 – salt score ≤20 response: patients who achieved salt score ≤20 (no more than 20% scalp hair loss) at week 52 – intermediate response: patients who failed to reach salt score ≤20 at week 52 but achieved salt30 at ≥1 post-baseline visit – non-response: patients who never achieved salt score ≤20 or salt30 by week 52 ■ this analysis only included patients enrolled in the baricitinib 4-mg and 2-mg treatment arms at baseline (n=855, 71.3% of all enrolled patients) ■ data were pooled from brave-aa1 and brave-aa2 and summarized by response subgroup using descriptive statistics ■ proportion of patients achieving clinically meaningful improvement in eyebrow or eyelash regrowth at week 52, respectively, was assessed as: – clinro eb (0,1), with ≥2-point improvement from baseline (among patients with baseline scores ≥2) – clinro el (0,1), with ≥2-point improvement from baseline (among patients with baseline scores ≥2) ■ non-responder imputation was used for data censored after permanent study drug discontinuation or data collected remotely due to the covid-19 pandemic pooled bari 2-mg (n=340) and bari 4-mg (n=515) population from brave-aa1 and -aa2 salt score ≤20 response subgroupa intermediate response subgroupb non-response subgroupc bari 2-mg (n=77) bari 4-mg (n=201) bari 2-mg (n=97d) bari 4-mg (n=154e) bari 2-mg (n=166) bari 4-mg (n=160) proportion of patients in subgroups, n/n (%) 77/340 (22.6) 201/515 (39.0) 97/340 (28.5) 154/515 (29.9) 166/340 (48.8) 160/515 (31.1) age, years 37.6 (11.4) 36.7 (12.9) 38.2 (13.8) 37.6 (13.0) 38.9 (13.0) 37.1 (13.2) female, n (%) 54 (70.1) 132 (65.7) 52 (53.6) 88 (57.1) 106 (63.9) 89 (55.6) race, n (%) american indian or alaska native asian black native hawaiian or other pacific islander white multiple 1 (1.3) 34 (44.2) 1 (1.3) 0 41 (53.2) 0 3 (1.5) 71 (35.3) 12 (6.0) 0 111 (55.2) 4 (2.0) 3 (3.1) 31 (32.3) 4 (4.2) 1 (1.0) 57 (59.4) 0 1 (0.7) 60 (39.2) 11 (7.2) 1 (0.7) 79 (51.6) 1 (0.7) 1 (0.6) 60 (36.1) 14 (8.4) 1 (0.6) 87 (52.4) 3 (1.8) 4 (2.5) 50 (31.3) 23 (14.4) 0 77 (48.1) 6 (3.8) bmi, kg/m2 25.4 (4.8) 26.0 (5.1) 26.2 (4.8) 26.8 (5.6) 26.4 (5.8) 26.5 (4.9) duration of aa since onset, years 10.6 (9.4) 10.2 (10.5) 11.4 (11.0) 11.0 (10.5) 14.1 (11.0) 14.8 (11.8) duration of current aa episode, n (%) <4 years ≥4 years 65 (84.4) 12 (15.6) 151 (75.1) 50 (24.9) 67 (69.1) 30 (30.9) 102 (66.2) 52 (33.8) 98 (59.0) 68 (41.0) 76 (47.5) 84 (52.5) baseline disease characteristics by salt score response subgroup pooled bari 2-mg (n=340) and bari 4-mg (n=515) population from brave-aa1 and -aa2 salt score ≤20 response subgroupa intermediate response subgroupb non-response subgroupc bari 2-mg (n=77) bari 4-mg (n=201d) bari 2-mg (n=97) bari 4-mg (n=154e) bari 2-mg (n=166) bari 4-mg (n=160f) salt score 76.9 (19.1) 80.6 (18.8) 84.4 (19.0) 84.4 (17.9) 91.7 (14.7) 91.4 (15.7) salt category, n (%) severe (salt score 50-94) very severe (salt score 95-100) 53 (68.8) 24 (31.2) 127 (63.2) 74 (36.8) 45 (46.4) 52 (53.6) 77 (50.0) 77 (50.0) 49 (29.5) 117 (70.5) 44 (27.5) 116 (72.5) clinro eb, n (%) 0 1 2 3 23 (29.9) 9 (11.7) 16 (20.8) 29 (37.7) 53 (26.5) 28 (14.0) 49 (24.5) 70 (35.0) 19 (19.6) 14 (14.4) 23 (23.7) 41 (42.3) 29 (19.0) 21 (13.7) 39 (25.5) 64 (41.8) 21 (12.7) 14 (8.4) 42 (25.3) 89 (53.6) 18 (11.4) 13 (8.2) 34 (21.5) 93 (58.9) clinro el, n (%) 0 1 2 3 33 (42.9) 9 (11.7) 10 (13.0) 25 (32.5) 72 (36.0) 24 (12.0) 51 (25.5) 53 (26.5) 30 (30.9) 11 (11.3) 21 (21.6) 35 (36.1) 42 (27.5) 23 (15.0) 37 (24.2) 51 (33.3) 34 (20.5) 23 (13.9) 30 (18.1) 79 (47.6) 33 (20.9) 10 (6.3) 29 (18.4) 86 (54.4) data are mean (standard deviation) unless stated otherwise a patients who achieved salt score ≤20 (no more than 20% scalp hair loss) at week 52; b patients who failed to reach salt score ≤20 but achieved salt30 at ≥1 post-baseline visit; c patients who never achieved salt score ≤20 or salt30 by week 52; d n=200 for clinro eb; e n=153 for clinro eb; f n=158 for clinro eb demographics and baseline characteristics by salt score response subgroup ■ the higher proportion of female patients in the responder subgroup compared with intermediate responders and compared with the overall population suggests a potential contribution of undiagnosed androgenetic alopecia to overall hair loss in male patients ■ responders and intermediate responders tended to have shorter duration of disease and current aa episode at baseline compared with non-responders ■ baseline severity of scalp, eyebrow, and eyelash hair loss was higher in the non-response subgroup note: analysis population included patients with baseline clinro eb and/or el scores ≥2 a patients who achieved salt score ≤20 (no more than 20% scalp hair loss) at week 52; b patients who failed to reach salt score ≤20 but achieved salt30 at ≥1 post-baseline visit; c patients who never achieved salt score ≤20 or salt30 by week 52 an oral, selective tyrosine kinase 2 inhibitor, bms-986165, improves quality of life in psoriasis: results from a phase 2 study fall clinical dermatology conference • october 17–20, 2019 • las vegas, nv, usa d thaçi,1 k papp,2 k gordon,3 a morita,4 m gooderham,5 p foley,6 e alemao,7 r kisa,7 y elbez,8 h ren,7 s banerjee7 1university of lübeck, lübeck, germany; 2k papp clinical research and probity medical research, waterloo, on, canada; 3medical college of wisconsin, milwaukee, wi, usa; 4nagoya city university graduate school of medical sciences, nagoya, japan; 5skin centre for dermatology, queen’s university and probity medical research, peterborough, on, canada; 6the university of melbourne, st vincent’s hospital melbourne & probity medical research, skin & cancer foundation inc, melbourne, victoria, australia; 7bristol-myers squibb, princeton, nj, usa; 8excelya, boulogne-billancourt, france • psoriasis is a chronic immune-mediated disease, which impairs patients’ physical health and worsens their health-related quality of life (qol).1–3 • improvement in health-related qol, as measured by the dermatology life quality index (dlqi),4 is an important patient-reported outcome in psoriasis trials. ○ the dlqi questionnaire includes 10 questions on how much the skin problem affected life over the previous week. ○ dlqi overall (total) scores range from 0 to 30, with higher scores indicating worse health-related qol.4 • bms-986165 is an oral, selective inhibitor of tyrosine kinase 2, an intracellular kinase that activates cytokine signaling pathways of interleukin-23 and type i interferons that are central in the pathophysiology of psoriasis5,6 and other immune-mediated disorders.7,8 • in a 12-week, placebo-controlled, phase 2 trial (nct02931838), bms-986165 was effective and demonstrated acceptable safety in patients with moderate to severe plaque psoriasis.9 ○ with bms-986165 at doses 3 mg twice daily (bid), 67–75% of patients achieved psoriasis area and severity index (pasi) 75 at week 12 (primary endpoint), versus 7% of those treated with placebo (p0.001). ○ pasi 75 and pasi 90 responses were similar in the highest dose groups (3 mg bid, 6 mg bid, 12 mg once daily [qd]), providing the rationale for combining data from these 3 groups in subsequent analyses.9 introduction • to evaluate: ○ dlqi responses, both overall and for individual questions, and ○ the time course of dlqi improvements and pasi or static physicians global assessment (spga) score of 0 or 1 (0/1) responses objective study design, endpoints, and patients • in this phase 2 trial, adults with moderate to severe plaque psoriasis were randomized equally to receive 1 of 5 bms-986165 doses or placebo for 12 weeks (figure 1). analysis of dlqi score • the proportion of patients achieving dlqi overall score 0/1, indicative of no impact on the patient’s health-related qol,10 over time to week 12 was calculated. • changes from baseline in dlqi overall score over time to week 12 were computed. ○ for patients with dlqi overall scores 2 at baseline, scores of 0/1 to individual questions on the 10-question dlqi form (each scored 0–3) were analyzed. ○ in addition, scores of 0 for question 1 were analyzed in a similar fashion. • a score of 0 on dlqi question 1 reflects the effect of the most relevant symptoms of psoriasis (itching, soreness, skin pain, and stinging) on health-related qol. • time courses of pasi 75, pasi 90, spga 0/1, and dlqi were analyzed. methods improvement in the overall dlqi score and individual dlqi questions over time • change from baseline over time to week 12 in the overall dlqi scores were more pronounced with the higher doses of bms-986165 versus placebo (figure 2). • in patients with a baseline dlqi score of 2 for an individual question, 85.7–97.4% in the combined dose group versus 42.9–76.9% in the placebo group improved to a score of 0/1 for that question at week 12 (figure 3). time course analysis of dlqi, pasi 75, pasi 90, and spga 0/1 • an improvement as early as week 4 (earliest time point evaluated) was observed in the proportion of patients attaining scores of 0/1 on dlqi overall (figures 4a, 5a, and 6a), and a score of 0 (‘not at all’) on the individual dlqi question 1 (‘how itchy, sore, painful, or stinging has your skin been?’), which reflects the most relevant subjective symptoms of psoriasis (figures 4b, 5b, and 6b). • at week 12, the proportion of patients with a score of 0/1 on dlqi overall and 0 on question 1 was as high as 64% and 59%, respectively, in the combined bms-986165 dose group versus 4% and 9%, respectively, with placebo. • improvements in scores of 0/1 on dlqi overall or 0 on dlqi question 1 occurred concordantly with improvements in pasi 75 (figure 4), pasi 90 (figure 5), and spga 0/1 (figure 6) with each dose over time. patients • overall, 267 patients were randomized and treated in this study, and 224 (84%) completed the 12-week treatment period. ○ 134 patients were included in the 3 highest dose groups, 3 mg bid (n=45), 6 mg bid (n=45), and 12 mg qd (n=44), which had similar pasi responses; 45 patients were included in the placebo group. • patient demographics and disease characteristics, including baseline dlqi scores, were generally comparable across treatment groups.9 ○ baseline mean (standard deviation) dlqi scores were as follows: placebo: 12.6 (7.1); 3 mg bid: 12.5 (5.5); 6 mg bid: 11.3 (6.5); 12 mg qd: 13.0 (7.4). results references 1. mahil sk et al. semin immunopathol. 2016;38:11-27. 2. armstrong aw et al. plos one. 2012;7:e52935. 3. dubertret l et al. br j dermatol. 2006;155:729-736. 4. finlay ay, khan gk. clin exp dermatol. 1994;19:210-216. 5. tokarski js et al. j biol chem. 2015;290:11061-11074. 6. gillooly k et al. arthritis rheumatol. 2016;68(suppl 10):abstract 11l. 7. harden jl et al. j autoimmun. 2015;64:66-73. 8. yao y et al. plos one. 2008;3:e2737. 9. papp k et al. n engl j med. 2018;379:1313-1321. 10. hongbo y et al. j invest dermatol. 2005;125:659-664. acknowledgments this study was sponsored by bristol-myers squibb. professional medical writing and editorial assistance was provided by katerina kumpan, phd, at caudex and was funded by bristol-myers squibb. disclosures dt: grant/research support: abbvie, almirall, amgen, biogen idec, bioskin, boehringer ingelheim, bristol-myers squibb, celgene, chugai, dermira, dignity, eli lilly, forward pharma, glaxosmithkline, janssen cilag, leo pharma, novartis, pfizer, regeneron, roche, sanofi, sandoz-hexal, ucb; consultant: abbvie, almirall, bristol-myers squibb, celgene, dignity, galapagos, leo pharma, lilly, novartis, pfizer, ucb; honoraria: abbvie, almirall, amgen, bioskin, celgene, dignity, janssen, la roche posay, leo pharma, merck sharp & dohme, novartis, pfizer, sandoz-hexal, sanofi, ucb; advisory board: abbvie, bioskin, bristol-myers squibb, celgene, dignity, eli lilly, galapagos, glaxosmithkline, janssen cilag, leo pharma, morphosys, novartis, pfizer, sandoz, sanofi, ucb. kap: speakers bureau: abbvie, amgen, astellas, celgene, eli lilly, galderma, janssen, kyowa hakko kirin, leo pharma, merck (merck sharp & dohme), novartis, pfizer, valeant; grant/research support: abbvie, akros, allergan, amgen, anacor, arcutis, astrazeneca, baxalta, boehringer ingelheim, bristol-myers squibb, celgene, coherus, dermira, dow pharma, eli lilly, galderma, genentech, glaxosmithkline, janssen, kyowa hakko kirin, leo pharma, medimmune, meiji seika pharma, merck serono, novartis, pfizer, regeneron, roche, sanofi-aventis/genzyme, takeda, ucb, valeant; consultant: abbvie, akros, amgen, arcutis, astellas, astrazeneca, baxalta, baxter, boehringer ingelheim, bristol-myers squibb, canfite, celgene, coherus, dermira, dow pharma, eli lilly, forward pharma, galderma, genentech, janssen, kyowa hakko kirin, leo pharma, meiji seika pharma, merck (merck sharp & dohme), merck serono, mitsubishi pharma, novartis, pfizer, regeneron, roche, sanofi-aventis/genzyme, takeda, ucb, valeant; honoraria: abbvie, akros, amgen, baxter, boehringer ingelheim, celgene, coherus, eli lilly, forward pharma, galderma, glaxosmithkline, janssen, kyowa hakko kirin, merck (merck sharp & dohme), merck serono, novartis, pfizer, takeda, ucb, valeant; scientific officer/steering committee/advisory board: abbvie, akros, amgen, anacor, astellas, baxter, boehringer ingelheim, bristol-myers squibb, celgene, dow pharma, eli lilly, galderma, janssen, kyowa hakko kirin, merck (merck sharp & dohme), merck serono, novartis, pfizer, regeneron, sanofi-aventis/genzyme, valeant. kg: grant/research support, consultant: abbvie, almirall, amgen, boehringer ingelheim, bristol-myers squibb, celgene, dermira, eli lilly, janssen, novartis, pfizer, sun, ucb. am: grant/research support, consultant, speakers bureau: abbvie, eli lilly, janssen, kyowa hakko kirin, leo pharma, maruho, mitsubishi-tanabe, novartis. mg: speakers bureau, consultant, investigator/advisor: abbvie, akros, amgen, arcutis, boehringer ingelheim, bristol-myers squibb, celgene, dermira, eli lilly, galderma, glaxosmithkline, incyte, janssen, kyowa hakko kirin, leo pharma, merck, medimmune, novartis, pfizer, regeneron, roche, sanofi genzyme, takeda, ucb, valeant. pf: speakers bureau, consultant, investigator, advisor, travel grants: 3m/inova/valeant, abbott/abbvie, amgen, biogen idec, boehringer ingelheim, botanix, bristol-myers squibb, celgene, celtaxsys, csl, cutanea, dermira, eli lilly, galderma, glaxosmithkline/stiefel, janssen, leo pharma/peplin, novartis, regeneron, sanofi genzyme, schering-plough/merck sharp & dohme, sun pharma, ucb, wyeth/pfizer. ea, rk, hr, sb: employees, shareholders: bristol-myers squibb. ye: consultant: bristol-myers squibb. previously presented at the european academy of dermatology and venerology (eadv), held october 9–13, 2019. • treatment with bms-986165 improved health-related qol, as measured by the proportions of patients in whom the disease had no impact on health-related qol (scores of 0/1 for dlqi overall), as well as those without bothersome subjective symptoms of psoriasis (score of 0 for dlqi question 1). • improvements were seen as early as 4 weeks after starting treatment and were concordant with pasi 75, pasi 90, and spga 0/1 responses. • phase 3 studies in psoriasis (poetyk pso phase 3 program; nct03624127, nct03611751) are ongoing to further assess bms-986165 in larger groups of patients. conclusions bms-986165: 3 mg qod (n=44) screening day -28 4 weeks’ screening 12-week treatment phase 30-day safety follow-up • active moderate to severe psoriasis (pasi �12, bsa �10, spga �3) • total 267 patients week 1 day 1 first dose week 12 day 85 primary endpoint pasi 75 bms-986165: 3 mg qd (n=44) bms-986165: 3 mg bid (n=45) bms-986165: 6 mg bid (n=45) bms-986165: 12 mg qd (n=44) placebo (n=45) follow-up figure 1: study design. bid=twice daily; bsa=body surface area; pasi=psoriasis area and severity index; qd=every day; qod=every other day; spga=static physician global assessment. scientific content on-demand copies of this poster obtained through quick response (qr) code are for personal use only and may not be reproduced without permission from fall clinical dermatology conference and the authors of this poster. links are valid for 30 days after the congress presentation date. to receive a copy of this poster scan qr code via a barcode reader application m ea n ch an ge fr om b as el in e in d lq i week -20 -15 -10 -5 0 5 0 2 6 104 8 12 3 mg bid placebo 6 mg bid 12 mg qd bms-986165 figure 2: mean change from baseline in dlqi overall score over time. error bars represent sd. bid=twice daily; dlqi=dermatology life and quality index; qd=every day; sd=standard deviation. patients (%) itchy, sore, painful, or stinging skin embarrassed/self-conscious limited activities like shopping, or looking after home or garden skin influenced clothes you wear affected social or leisure activities limited sports prevented you from working or studying created problems with your partner, close friends, or relatives caused sexual difficulties treatment for your skin has been a problem 0 10 20 30 40 50 60 70 80 90 100 placebo bms-986165 combined* figure 3: frequency of patients with response of 0/1 on individual dlqi questions at week 12 among those with response of 2 for that question at baseline (from patients who had dlqi overall score 2 at baseline). *bms-986165 3 mg bid, 6 mg bid, and 12 mg qd combined. bid=twice daily; dlqi=dermatology life and quality index; qd=every day. 0 10 20 30 40 50 60 70 80 90 100 0 2 4 6 8 10 12 p at ie nt s (% ) weeks 0 10 20 30 40 50 60 70 80 90 100 0 2 4 6 8 10 12 p at ie nt s (% ) weeks dlqi overall: score 0/1pasi 75 3 mg bid (n=45) placebo (n=45) 6 mg bid (n=45) 12 mg qd (n=44) bms-986165 dlqi question 1*: score 0pasi 75 3 mg bid (n=45) placebo (n=45) 6 mg bid (n=45) 12 mg qd (n=44) bms-986165 a b figure 4: time course of pasi 75 and (a) dlqi overall or (b) dlqi question 1* responses. *question 1 states, ‘over the last week, how itchy, sore, painful, or stinging has your skin been?’ bid=twice daily; dlqi=dermatology life and quality index; pasi 75=75% improvement in psoriasis area and severity index score; qd=every day. figure 5: time course of pasi 90 and (a) dlqi overall or (b) dlqi question 1* responses. figure 6: time course of spga 0/1 and (a) dlqi overall or (b) dlqi question 1* responses. *question 1 states, ‘over the last week, how itchy, sore, painful, or stinging has your skin been?’ bid=twice daily; dlqi=dermatology life and quality index; pasi 90=90% improvement in psoriasis area and severity index score; qd=every day. *question 1 states, ‘over the last week, how itchy, sore, painful, or stinging has your skin been?’ bid=twice daily; dlqi=dermatology life and quality index; qd=every day; spga=static physicians global assessment. 0 10 20 30 40 50 60 70 80 90 100 0 2 4 6 8 10 12 p at ie nt s (% ) weeks 0 10 20 30 40 50 60 70 80 90 100 0 2 4 6 8 10 12 p at ie nt s (% ) weeks dlqi overall: score 0/1pasi 90 3 mg bid placebo 6 mg bid 12 mg qd bms-986165 3 mg bid placebo 6 mg bid 12 mg qd bms-986165 dlqi question 1*: score 0pasi 90 a b 0 10 20 30 40 50 60 70 80 90 100 0 2 4 6 8 10 12 p at ie nt s (% ) weeks 0 10 20 30 40 50 60 70 80 90 100 0 2 4 6 8 10 12 p at ie nt s (% ) weeks dlqi overall: score 0/1spga 0/1 dlqi question 1*: score 0spga 0/1 a b 3 mg bid placebo 6 mg bid 12 mg qd bms-986165 3 mg bid placebo 6 mg bid 12 mg qd bms-986165 presented at the fall clinical dermatology conference, october 17–20, 2019, las vegas, nv, usa synopsis • lidose-isotretinoin 40 mg, unlike traditional isotretinoin, does not require administration with a high-fat, high-calorie meal to optimize bioavailability and efficacy because it is presolubilized in a lipid matrix1,2 • a novel low-dose micronized-isotretinoin 32-mg formulation has been developed by adopting an optimized micronization technology that substantially increases the surface area per unit mass of the drug in formulation objectives • to evaluate the bioavailability of micronized-isotretinoin 32 mg compared with lidose-isotretinoin 40 mg under fed and fasted conditions in healthy participants • to assess the effect of food on the bioavailability of micronized-isotretinoin 32 mg in healthy participants methods • this analysis includes data from 2 open-label, randomized crossover studies in healthy volunteers: the fed bioequivalence and food-effect study and the fasting study • eligible participants were healthy men (both studies) and women (fed bioequivalence and food-effect study only) ≥18 years of age with body mass index between 18 and 30 kg/m2 – male participants were required to use a reliable form of contraception throughout the study, and female participants were required to be of nonchildbearing potential (defined as naturally postmenopausal [no menses] for at least 2 years before initial dosing with a documented follicle-stimulating hormone level ≥40 miu/ml at screening or surgically postmenopausal/sterile [eg, bilateral oophorectomy, tubal ligation, or hysterectomy], with the procedure performed at least 6 months before initial dosing) • exclusion criteria for both studies included: – history of allergy or sensitivity to retinoids or vitamin a – significant history or current evidence of chronic infectious disease system disorders or organ dysfunction – history or presence of gastrointestinal disease or inflammatory bowel disease or a history of malabsorption in the previous year – history (personal or family) of psychiatric disorders in the last 2 years requiring treatment or hospitalization – presence of a medical condition requiring regular treatment with prescription drugs – history of excessive alcohol consumption or any drug or alcohol addiction that required treatment during the previous 12 months treatments • fed bioequivalence and food-effect study – multicenter, 3-treatment, 3-period, 6-sequence crossover study in which participants were randomized to 1 of 6 possible sequences that each included 3 periods of treatment: • fasted-state micronized-isotretinoin 32 mg: a single dose of micronizedisotretinoin 32 mg following an overnight fast (defined as no food or beverage intake other than water) of at least 10 hours • fed-state micronized-isotretinoin 32 mg: a single dose of micronized isotretinoin 32 mg following a standardized high-fat, high-calorie breakfast (2 fried eggs, 2 strips of bacon, 4 oz of hash browns, 2 slices of buttered toast, and 8 oz of whole milk; this food and drug administration standard meal contained about 150 protein calories, 250 carbohydrate calories, and 500 fat calories) preceded by an overnight fast of at least 10 hours • fed-state lidose-isotretinoin 40 mg: a single dose of lidose-isotretinoin 40 mg following a standardized high-fat, high-calorie breakfast preceded by an overnight fast of at least 10 hours • fasting study – single-center, 2-treatment, 2-period, 2-sequence crossover study in which participants were randomized to 1 of 2 possible sequences that each included 2 periods of treatment: • fasted-state micronized-isotretinoin 32 mg: a single dose of micronizedisotretinoin 32 mg following an overnight fast of at least 10 hours • fasted-state lidose-isotretinoin 40 mg: a single dose of lidose-isotretinoin 40 mg following an overnight fast of at least 10 hours • the interval between dosing was 21 days in both studies • blood samples were collected before dosing to establish endogenous isotretinoin levels and then at intervals over the 96 hours postdosing references 1. colburn w, et al. j clin pharmacol. 1983;23:534–539. 2. webster g, et al. j am acad dermatol. 2013;69:762–767. 3. roche laboratories inc. accutane® (isotretinoin capsules) pi. november 2008. 4. sun pharmaceutical industries, inc. absorica® (isotretinoin capsules) pi. august 2018. acknowledgments we thank the participants for their involvement in these studies. these studies were funded by sun pharmaceutical industries ltd, gurgaon, haryana, india. editorial support was provided by jk associates, inc., part of the fishawack group of companies, and was funded by sun pharmaceutical industries, inc. statistical support was provided by novum pharmaceutical research services, inc., and was funded by sun pharmaceutical industries ltd. disclosures sm and sk are employees of sun pharmaceutical industries ltd. js is an employee of sun pharmaceutical industries, inc. comparative pharmacokinetic profiles of a novel low-dose micronized-isotretinoin 32-mg formulation and lidose-isotretinoin 40 mg in fed and fasted conditions: 2 open-label, randomized crossover studies in healthy adult participants sumit madan,1 sudershan kumar,2 jeanett segal3 1research and development centre, sun pharmaceutical industries ltd, gurgaon, haryana, india; 2clinical pharmacology and pharmacokinetics, sun pharmaceutical industries ltd, gurgaon, haryana, india; 3sun pharmaceutical industries, inc., princeton, nj, usa endpoints • fed bioequivalence and food-effect study – relative bioavailability of micronized-isotretinoin 32 mg compared with lidose-isotretinoin 40 mg in the fed state – effect of food on the bioavailability of micronized-isotretinoin 32 mg • fasting study – relative bioavailability of micronized-isotretinoin 32 mg compared with lidoseisotretinoin 40 mg in the fasted state • in both studies, safety was determined by the evaluation of adverse events (aes) statistical analysis • for all treatments, bioavailability was measured using baseline-adjusted logtransformed maximum isotretinoin plasma concentration (lncmax) and baseline-adjusted log-transformed area under the plasma concentration-time curve from time 0 to last measurable isotretinoin concentration (lnauc0–t) and from time 0 to infinity (lnauc0–∞) – for comparison of fed-state micronized-isotretinoin 32 mg with fed-state lidoseisotretinoin 40 mg, bioequivalence was determined if the 90% confidence intervals (cis) on the least squares geometric mean (lsgm) ratios for each parameter fell within the 80.0%–125.0% range – absorption rate in the fasted state was compared between micronized isotretinoin 32 mg and lidose-isotretinoin 40 mg by post hoc partial area evaluation from dose to cmax, after cmax to 12 hours, and from 12 hours to 24 hours • analysis of variance was performed for both studies, testing 2 1-sided hypotheses at the α=0.05 level of significance using sas® (sas institute inc., cary, nc, usa), with the general linear model procedure used for the fasting study and a mixed procedure used for the fed bioequivalence and food-effect study • data from participants with some missing data were used if pharmacokinetic parameters could be estimated using the remaining data points; otherwise, data from these participants were excluded from the final analysis results • in the fed bioequivalence and food-effect study, 71 participants enrolled and 65 were included in the analyses – reasons for discontinuation were voluntary withdrawal (5 participants), positive substance abuse screen (2 participants), noncompliance with breakfast requirements (2 participants), and loss to follow-up (1 participant) • in the fasting study, 18 participants enrolled and all were included in the analyses • baseline demographics for participants in both studies are presented in table 1 • 90% cis for the lsgm ratios for the baseline-adjusted lnauc0–t (91.9%–98.4%), lnauc0–∞ (91.5%–98.0%), and lncmax (96.3%–112.6%) for fed-state micronizedisotretinoin 32 mg vs fed-state lidose-isotretinoin 40 mg all fell within the 80.0%–125.0% range for bioequivalence, showing that micronized-isotretinoin 32 mg is bioequivalent to lidose-isotretinoin 40 mg under fed conditions (table 2, figure 1a) • baseline-adjusted lsgm ratios for fasted-state micronized-isotretinoin 32 mg vs fasted-state lidose-isotretinoin 40 mg show that micronized-isotretinoin 32 mg had approximately 2 times higher bioavailability than lidose-isotretinoin 40 mg under fasted conditions (table 3, figure 1b) – partial area evaluation indicates that fasted-state micronized-isotretinoin 32 mg had higher absorption than fasted-state lidose-isotretinoin 40 mg in each segment from dose to cmax (lnauc0–4 lsgm ratio: 164.8%), after cmax to 12 hours (lnauc4–12 lsgm ratio: 206.1%), and from 12 hours to 24 hours (lnauc12–24 lsgm ratio: 200.3%) • administering micronized-isotretinoin 32 mg with a high-fat meal increased lnauc0–t and lnauc0–∞ by 24.8% and 23.2%, respectively, compared with administration in the fasted state, but had no effect on lncmax, indicating that food minimally affects the extent but not the rate of micronized-isotretinoin 32 mg absorption (table 4, figure 1a) • sixty-eight aes were reported by 36 of the 71 participants in the fed bioequivalence and food-effect study: 34 occurred after administration of fasted-state micronizedisotretinoin 32 mg, 16 after fed-state micronized-isotretinoin 32 mg, and 18 after fed-state lidose-isotretinoin 40 mg – headache was the most frequently reported ae, reported by 6, 3, and 2 participants following administration of fasted-state micronized-isotretinoin 32 mg, fed-state micronized-isotretinoin 32 mg, and fed-state lidose-isotretinoin 40 mg, respectively • in the fasting study, 7 aes were reported by 4 of the 18 participants (3 for fasted-state micronized-isotretinoin 32 mg and 4 for fasted-state lidose-isotretinoin 40 mg) – oropharyngeal pain was the most frequently reported ae, occurring in 1 participant following administration of fasted-state micronized-isotretinoin 32 mg and 1 participant following administration of fasted-state lidose-isotretinoin 40 mg • no serious aes were reported in either study conclusions • micronized-isotretinoin 32 mg is bioequivalent to lidose-isotretinoin 40 mg under fed conditions and is twice as bioavailable as lidose-isotretinoin 40 mg under fasted conditions • food has no effect on the rate and a marginal effect on the extent of micronizedisotretinoin 32 mg absorption, which is less than the effect on lidose-isotretinoin 40 mg and other marketed isotretinoin products3,4 table 1. baseline demographics fed bioequivalence and food-effect study fasting study fasted-state micronizedisotretinoin 32 mg (n=63) fed-state micronizedisotretinoin 32 mg (n=65) fed-state lidose isotretinoin 40 mg (n=63) fasted-state micronizedisotretinoin 32 mg (n=18) fasted-state lidose isotretinoin 40 mg (n=18) sex male female 47 (74.6) 16 (25.4) 49 (75.4) 16 (24.6) 47 (74.6) 16 (25.4) 18 (100) 0 18 (100) 0 race asian black white hispanic other 2 (3.2) 34 (54.0) 20 (31.8) 4 (6.4) 3 (4.8) 2 (3.1) 35 (53.9) 20 (30.8) 5 (7.7) 3 (4.6) 2 (3.2) 34 (54.0) 19 (30.2) 5 (7.9) 3 (4.8) 0 7 (38.9) 8 (44.4) 2 (11.1) 1 (5.6) 0 7 (38.9) 8 (44.4) 2 (11.1) 1 (5.6) age, y mean±sd median range 44.2±14.8 38.0 21–68 44.2±14.6 38.0 21–68 44.3±14.4 38.0 21–68 44.1±11.8 43.5 22–62 44.1±11.8 43.5 22–62 weight, lb mean±sd median range 169.4±27.0 165.0 90–225 169.5±27.2 165.0 90–225 169.9±27.6 166.0 90–225 175.3±28.1 180.5 133–232 175.3±28.1 180.5 133–232 bmi, kg/m2 mean±sd median range 25.5±2.9 26.1 18.2–30.0 25.4±3.0 26.1 18.2–30.0 25.5±3.0 26.1 18.2–30.0 25.5±2.9 24.9 20.4–29.8 25.5±2.9 24.9 20.4–29.8 tobacco user yes no 20 (31.8) 43 (68.3) 21 (32.3) 44 (67.7) 20 (31.8) 43 (68.3) 6 (33.3) 12 (66.7) 6 (33.3) 12 (66.7) data presented as n (%) unless otherwise stated. bmi, body mass index; n, number of participants in the treatment group; n, number of participants of a particular demographic; sd, standard deviation. table 2. baseline-adjusted plasma isotretinoin concentrations for fed-state micronized-isotretinoin 32 mg and fed-state lidose-isotretinoin 40 mg (fed bioequivalence and food-effect study) parameter treatment arithmetic mean±sd (% cv) lsgm participants contrasted, na lsgm ratio (%) 90% confidence interval (%) p-value sequence auc0–t (h·ng/ml) fed-state micronized-isotretinoin 32 mg 10,209.1±1967.5 (19.3) 9915 61 95.07 91.88–98.36 0.1327 fed-state lidose-isotretinoin 40 mg 10,693.0±2247.3 (21.0) 10,430 auc0–∞ (h·ng/ml) fed-state micronized-isotretinoin 32 mg 10,921.9±2176.1 (19.9) 10,654 61 94.71 91.51–98.02 0.1940 fed-state lidose-isotretinoin 40 mg 11,676.6±2851.0 (24.4) 11,249 cmax (ng/ml) fed-state micronized-isotretinoin 32 mg 645.7±275.2 (42.6) 596.7 63 104.09 96.27–112.55 0.4744 fed-state lidose-isotretinoin 40 mg 595.7±183.8 (30.9) 573.2 anumber of participants contrasted represents the number of participants who had data for this parameter in each treatment group. auc0–t, area under the plasma concentration-time curve from time 0 to the last measurable concentration; auc0–∞, area under the plasma concentrationtime curve from time 0 to infinity; cmax, maximum measured plasma concentration; cv, coefficient of variation; lsgm, least squares geometric mean; sd, standard deviation. table 3. baseline-adjusted plasma isotretinoin concentrations for fasted-state micronized-isotretinoin 32 mg and fasted-state lidose-isotretinoin 40 mg (fasting study) parameter treatment arithmetic mean±sd (% cv) lsgm participants contrasted, na lsgm ratio (%) 90% confidence interval (%) p-value sequence auc0–t (h·ng/ml) fasted-state micronized-isotretinoin 32 mg 7485.1±1693.9 (22.6) 7289 18 198.62 175.19–225.17 0.9168 fasted-state lidose-isotretinoin 40 mg 3833.6±1160.7 (30.3) 3670 auc0–∞ (h·ng/ml) fasted-state micronized-isotretinoin 32 mg 8016.3±1800.4 (22.5) 7807 18 196.33 172.86–222.98 0.7367 fasted-state lidose-isotretinoin 40 mg 4164.2±1294.4 (31.1) 3977 cmax (ng/ml) fasted-state micronized-isotretinoin 32 mg 539.0±180.3 (33.5) 507.6 18 219.63 187.26–257.60 0.4234 fasted-state lidose-isotretinoin 40 mg 238.2±60.8 (25.5) 231.1 anumber of participants contrasted represents the number of participants who had data for this parameter in each treatment group. auc0–t, area under the plasma concentration-time curve from time 0 to the last measurable concentration; auc0–∞, area under the plasma concentrationtime curve from time 0 to infinity; cmax, maximum measured plasma concentration; cv, coefficient of variation; lsgm, least squares geometric mean; sd, standard deviation. table 4. baseline-adjusted plasma isotretinoin concentrations for fasted-state micronized-isotretinoin 32 mg and fed-state micronized-isotretinoin 32 mg (fed bioequivalence and food-effect study) parameter treatment arithmetic mean±sd (% cv) lsgm participants contrasted, na lsgm ratio (%) 90% confidence interval (%) p-value sequence auc0–t (h·ng/ml) fasted-state micronized-isotretinoin 32 mg 8466.3±2458.2 (29.0) 8042 63 124.84 117.29–132.88 0.0351 fed-state micronized-isotretinoin 32 mg 10,209.1±1967.5 (19.3) 10,039 auc0–∞ (h·ng/ml) fasted-state micronized-isotretinoin 32 mg 9219.1±2782.1 (30.2) 8711 62 123.24 115.93–131.01 0.0600 fed-state micronized-isotretinoin 32 mg 10,921.9±2176.1 (19.9) 10,736 cmax (ng/ml) fasted-state micronized-isotretinoin 32 mg 611.3±285.2 (46.6) 539.4 63 108.25 94.42–124.12 0.2908 fed-state micronized-isotretinoin 32 mg 645.7±275.2 (42.6) 583.9 anumber of participants contrasted represents the number of participants who had data for this parameter in each treatment group. auc0–t, area under the plasma concentration-time curve from time 0 to the last measurable concentration; auc0–∞, area under the plasma concentrationtime curve from time 0 to infinity; cmax, maximum measured plasma concentration; cv, coefficient of variation; lsgm, least squares geometric mean; sd, standard deviation. figure 1. mean baseline-adjusted plasma isotretinoin concentration vs time curves for (a) fasted-state micronized-isotretinoin 32 mg, fed-state micronized-isotretinoin 32 mg, and fed-state lidose-isotretinoin 40 mg (fed bioequivalence and food-effect study) and (b) fasted state micronized-isotretinoin 32 mg and fasted-state lidose-isotretinoin 40 mg (fasting study) c on ce nt ra tio n (n g/ m l) 500 400 300 200 100 0 0 10 20 30 40 50 60 70 80 90 100 hours after dosing c on ce nt ra tio n (n g/ m l) 500 400 300 200 100 0 0 10 20 30 40 50 60 70 80 90 100 hours after dosing fasted-state micronized-isotretinoin 32 mg (n=18) fasted-state lidose-isotretinoin 40 mg (n=18) fasted-state micronized-isotretinoin 32 mg (n=63) fed-state micronized-isotretinoin 32 mg (n=65) fed-state lidose-isotretinoin 40 mg (n=63) a b skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 200 in-depth reviews a review of exogenous factors implicated in the induction of cutaneous melanoma jacob m. hands1, lawrence s. moy2 1university of california, berkeley, ca 2advanced aesthetics & cosmetic dermatology, university of california, los angeles, ca melanoma is an increasingly pervasive form of malignant skin cancer. cases of cutaneous melanoma are on the rise across ages and global populations, with incidence increasing 1.6% and 1.5% per annum for men and women respectively –– the single largest increase in “common cancers” among men, and the next leading malignancy among women.1 accordingly, the identification of modifiable behaviors is of paramount concern. previous reviews have focused on specific risk factors (e.g. uvr, pollution, diet, hormonal supplementation) to the near exclusion of other contributory factors. this review strives to report an inclusive range of exogenous variables linked to cutaneous melanoma incidence. in this review, we examine the various contributions of exogenous factors linked to the induction of cutaneous melanoma. factors for consideration include but are not limited to: long-wave ultraviolet a (uva), short-wave ultraviolet b (uvb), hormonal supplementation, diet, smoking, alcohol, vitamin supplementation, ionizing radiation, pollution and chemical exposure. introduction melanoma is an increasingly pervasive form of malignant skin cancer. cases of cutaneous melanoma are on the rise across ages and global populations, with incidence increasing significantly for both men and women. accordingly, the identification of modifiable behaviors is of paramount concern. previous reviews have focused on specific risk factors (e.g. uvr, pollution, diet, hormonal supplementation) to the near exclusion of other contributory factors. this review strives to report an inclusive range of exogenous variables linked to cutaneous melanoma incidence. in this review, we examine the various contributions of exogenous factors linked to the induction of cutaneous melanoma. factors for consideration include but are not limited to: long-wave ultraviolet a (uva), short-wave ultraviolet b (uvb), hormonal supplementation, diet, smoking, alcohol, vitamin supplementation, ionizing radiation, pollution, and chemical exposure. abstract skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 201 uva (>315–400 nm) uvb (>280 to 315 nm) uvc (200-280 nm) scope & frame broadly, ultraviolet radiation (uvr) can be defined as wavelengths nested between those of the visible and the x-ray on the spectrum of electromagnetic radiation. uvr can be segmented into three distinct subtypes: ultraviolet a, ultraviolet b, and ultraviolet-c. as each wavelength passes through our atmosphere, it is absorbed to varying degrees by extent ozone. while ozone is near impenetrable to uvc and, to a lesser extent uvb, it is notably porous with respect to uva.2 as such, our analysis will focus on uvr subtypes that are likely to be encountered and, hence, contributory. thus, what we refer to as uvr will denote the mutual contribution of uva & uvb. uvr has long been implicated in melanomagenesis.3,4 it has been estimated that uvr exposure alone can account for ~60-70% of all cases of cutaneous melanoma.5 uvr exposure is considered the predominant exogenous driver of all cutaneous melanoma cases.6 however, the role of uvr in the induction of cutaneous melanoma is less apparent. uvr’s role in the pathogenesis of cutaneous melanoma pervades academic journals. these views have evolved over the course of decades. research spanning the early 1970s to late 1980s would attribute cutaneous melanoma cases to periods of intense exposure to uvb radiation.7 similarly, uva was considered an insufficient means of induction because it was unable to directly alter dna and generate mutagenic species thought necessary to the pathogenesis of cutaneous melanoma.8 discussion in the following decades (1990s-present) would both confirm and reject previous hypotheses regarding the role of uvr in melanomagenesis.9-11 though uvb was confirmed as a possible exogenous driver of cutaneous melanoma, uva emerged as an additional exogenous factor for consideration. uvb uvb’s role in melanomagenesis is seldom disputed. though uvb is estimated to account for less than 5% of all solar radiation, it’s role in the induction of cutaneous melanoma is pronounced. uvb has been shown to induce dna lesions directly via cyclobutane pyrimidine dimers (cpds) and photoproducts (6-4 pps) in addition to immunosuppression mechanisms.3 evidence suggests that uvb is more likely absorbed in the basal layer of the epidermis through the stratum corneum, while uva penetrates further into dermal layers (e.g. stroma).12 uvb is uniquely implicated in direct mutagenesis involved in cutaneous melanoma via c > t base changes following photochemical reaction. animal and fish models which incorporate uvb mimics find that uvb exposure can induce cutaneous melanoma.9,13 prenatal exposure to uvb photo-mimics in animal models were originally considered necessary in the induction of cutaneous melanoma. modern research has found that induction of cutaneous melanoma via uvb sources can take place even after adolescence.14 while uvb is a likely motivator in melanomagenesis, there remain questions as to the precise mechanisms which initiate conversion of at risk cells. for instance, authors have noted that although uvb can alter dna directly through cpds, dna modification often occurs at the 3’end of the strand.13 such unexpected outcomes uva & uvb skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 202 may warrant additional exploration into the particular pathways implicated in cutaneous melanoma induction. uvb is a popular explanatory mechanism for increased relative risk for cutaneous melanoma following acute sunburns. it is suggested that while cutaneous melanoma risk is modestly associated with cumulative solar exposure and sun burn jointly, the risk conferred by multiple sunburns, or periods of high intermittent uv exposure, especially in youth, are significant risk factors, with risk increasing as the quantity of lifetime sunburns increases.14,15 per meta-analysis performed by dennis et al. (n = 104 studies) sunburn exposure significantly increased a subject’s overall risk (or) of cutaneous melanoma –– or was further stratified by age (childhood = 1.8, or adolescence = 1.7, or adulthood = 1.5) with the youngest populations afflicted with the highest overall risk following sunburn.15 there is some evidence to suggest that senescent populations face outsized sunburn risk.16 while uvb is an impressive catalyst in cutaneous melanoma induction, uva’s acute role in the pathogenesis of cutaneous melanoma renders it difficult to disentangle one form of uvr from another as a causal variable in the aftermath of acute sunexposure. furthermore, it is estimated that direct dna damage-induced cutaneous melanoma can only account for x < 8% of all cutaneous melanoma cases; 92% is attributed to indirect dna damage.17 uva initially, multiple models disputed the role of uva in the induction of cutaneous melanoma.18 uva radiation was considered insufficient in order to alter dna bases via cyclobutane pyrimidine dimers (cpds) and 6-4 photoproducts.9,13,18 transgenic mouse models, the american opossum, and the xiphforous-fish were recruited in support of this hypothesis.10,19-20 later findings would dispute these results, demonstrating the ability of uva to initiate cutaneous melanoma in multiple animal models via oxidative stress.9 uva is thought to induce cutaneous melanoma indirectly through reactive oxygen species (ros) and immunosuppression.21-23 in particular, it has been proposed that melanin acts as the key photosensitizer in the pathogenesis of cutaneous melanoma via ros.18 uva’s role in the pathogenesis of cutaneous melanoma appears infrequently contested in modern literature. current estimates suggest that relative abundance and penetration of uva is ~20x and ~90x greater than uvb in both atmospheric abundance and penetrative capacity respectively.24 and, while uvb may directly influence dna mutagenesis, it is unable to penetrate deep dermal layers, beyond the stratum corneum. uva, however, can penetrate well into the upper layers of the dermis/epidermis (beyond 100 µm) interacting with key target cells, including melanocytes.18 accordingly, increased nevus count is associated with uva exposure.25 uva’s ability to generate cutaneous melanoma indirectly through ros was proposed as explanatory in the sunscreen paradox (sp). the sunscreen paradox (sp) refers to findings at the turn of the millennium whereby it was observed that sunscreen use was positively associated with cutaneous melanoma.14,26 in recent years, the sp phenomenon has simmered with findings pointing to an agnostic link between prophylactic use of broad spectrum spf and incidence of cutaneous melanoma. a particularly vivid meta-analysis illustrates precipitously declining relative-risk (rr) values –– or the risk differential between exposed or unexposed groups –– over the last two decades vis-a-vis the sp skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 203 phenomenon.27 we agree with previous authors and propose that abatement of sp is resultant from the adoption of higher spf, broad-spectrum sunblocks that target uva/uvb in tandem. while early sunblocks focused on prevention of acute sunburn (conventionally associated with uvb) modern broad-spectrum composites target both uva & uvb.18, 27 it should be noted that other reviews have proposed alternative explanations for the sp phenomenon, including increased ros production owing to radical-producing interactions between metal oxides in sunscreen and uva/uvb.28 authors remark that although sunscreen is marketed as a benign prophylactic, it is unable to dissipate excitation.28 thus, subcutaneous sunscreen may magnify the impact of uvr on target cells. the sp is a significant phenomenon that merits further attention. this review briefly discusses its occurrence to evidence the role of uvr as an exogenous driver of cutaneous melanoma. evidence for the unique role of uva in the pathogenesis of cutaneous melanoma is not isolated to the sp phenomenon. further support for its paramount role in melanomagenesis can be found in epidemiologic data concerning the rise of popular indoor tanning devices (itds), or artificial sources of uva induced radiation therapy for cosmetic enhancement of pigmentation. indoor tanning devices rose to prominence in the early 1980s and 1990s. concomitant with their rise were higher incidences of both cutaneous melanoma and non-melanoma skin cancer (nmsc), though paradoxically no increase in skincancer related mortality was observed.29 several papers have attempted to explain this apparent paradox, with one proposing the existence of separate species of cutaneous melanoma –– superficial spreading types chiefly resultant from extreme uva exposure to melanocytes in adolescence and adulthood and more invasive types that arise from uvb exposure to melanocytes altered in adolescence and early adulthood.29 epidemiologic data marshalled in support of this hypothesis has failed to reject such findings.30, 31 indoor tanning devices, such as tanning beds, are significantly associated with cutaneous melanoma, especially if used before the age of 35.32, 33 moreover, rr associated with cutaneous melanoma induction appears dose-dependent, with the rr associated with cutaneous melanoma increasing by as much as 3.8% per tanning session.34 it is estimated that sunbeds deliver as much as 5-15x uva doses than that delivered by “midday sun” in the mediterranean (31° 40° latitude).29 itds appear strongly associated with cutaneous melanoma incidence. multiple findings document significantly increased cutaneous melanoma risk following use of itd facilities.35 incidence rates of cutaneous melanoma following the introduction of itds and facilities presage increased rates of cutaneous melanoma diagnosis. extent evidence suggests that itds are a powerful exogenous driver of cutaneous melanoma.36 thus, uva’s performance in the pathogenesis of cutaneous melanoma may be considered both relevant and significant. a final insight concerning uva’s distinct role in the pathogenesis of cutaneous melanoma can be found in the asymmetric lateral distribution of cutaneous melanoma and merkel cell carcinoma (mcc). it is reported that the typical “driver windshield” is unable to efficiently block longer wavelengths such as uva, though uvr shielding varies between front, rear, and driver’s side windshields.37 the latter being the most porous with respect to uva, estimated to allow up to 30% of emitted uva through its skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 204 surface.38 glass is able to effectively shield from shorter wavelength sources of radiation such as uvb, but not uva. anecdotally, it has been observed that truck driver’s (transportation carriers more generally) may be at higher risk for cutaneous melanoma. the subject, though of clinical interest, represents a lacuna in the current literature. a recent study by paulson, iyer, et al. demonstrated a marked difference in the lateral distribution of malignant melanoma (mm) and mcc.39 mms and ccs were more likely to appear on the driver’s left (53% v. 47%).40 left-side bias was highly significant.39 it should be noted that uv exposure on the left-side of the driver’s face is estimated at 20x in comparison to rightsided facial exposure of the driver.39 further inquiry into the matter appears prudent. uvr confounding uvr’s collective role as an exogenous driver of melanoma is manifest, though perhaps not definitive. for instance, while uvr can be causally associated with induction of cutaneous melanoma, there likely exist endogenous genetic interplays that moderate its influence. a variety of loci have been found that significantly increased cutaneous melanoma risk, independent of solar exposure. cdkn2a, m1cr, nras and braf are perhaps the most notorious agents considered involved in the pathogenesis of melanoma.13 cdk2na were identified by investigators tracking subjects afflicted with familial atypical multiple mole melanoma syndrome (fammm). both variants pertain to mitotic division, death, and senescence.41, 42 it is thought that carriers of these variants are particularly susceptible to solar exposure and may experience adverse reactions to prolonged sun exposure. other genetic disorders pertaining to nucleotide excision repair (ner) must be factored into any equation that attempts to assess the effect of solar radiation on cutaneous melanoma incidence. ner mutations are characterized by global failure to repair dna damage resulting from solar radiation exposure.43 examples of disorders characterized by ner defects include but are not limited to xeroderma pigmentosum (xp), trichothiodystrophy (ttd), and cockayne syndrome.18 it is beyond the scope of this paper to precisely estimate the impact of the aforementioned variants in the induction of cutaneous melanoma (though there is ample research which attempts to answer just that). in fact, a recent analysis of epigenetic interaction estimated the impact of uvrelated photo-damage in populations with alleles linked to melanoma incidence, concluding that individuals with abnormal variants with respect to mitf e318k, mc1r r-alleles, and the asip risk haplotype were more likely to exhibit multiple primary melanomas (mpms) than controls (or = 1.4-2.5).44 these considerations are broached to add dimensionality to our analysis. while uvr is almost assuredly a powerful exogenous driver of cutaneous melanoma, its role is complicated by genetic and hereditary confounds. indeed, uvr’s role in the pathogenesis of cutaneous melanoma remains unclear in certain contexts. it has been noted that cutaneous melanoma appears in areas not directly exposed to uvr, though uvr is considered an explanatory factor. scalp melanomas, for instance, have been linked to high levels of cumulative uvr exposure, signal a less optimistic prognosis and appear typically in senescent populations likely to have absorbed higher-than-average cumulative doses of uvr.45 the direct mechanism implicated in the exogenous pathogenesis of cutaneous melanoma in non-sun exposed regions remains illusory.46 it may be of clinical interest that incidence rates of head and neck melanomas have skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 205 increased amongst younger populations in recent years, notably males (18-29).47 higher uvr exposure has been proposed as a plausible explanatory factor.47 though absolute rates of head and neck melanoma tilt significantly towards male populations x > 50 years, such developments complicate extent theories regarding uvr exposure and the pathogenesis of cutaneous melanoma. additional confusion arises from clinical research suggesting that “sun exposure” in light skinned individuals “prone to tanning” (phototype ii -“unexposed skin is white, blue, hazel or brown eyes red, blonde or brown hair, european/scandinavian, phototype iii -“unexposed skin is fair, brown eyes, dark hair, southern or central european”) may actually be protective against the incidence of melanoma.48,49 the link between uvr exposure and realized uvr exposure is mediated by absorption ability, specifically relative concentrations of pheomelanin and eumelanin. pheomelanin and eumelanin are melanin subtypes linked to differential expression of the melanocortin-1 receptor (mc1r). whereas concentrations of pheomelanin are roughly equivalent in most populations, relative concentrations of eumelanin differ considerably, with higher phototypes expressing more eumelanin than lower phototypes.3 subjects with lower concentrations of eumelanin tend to be at higher risk for cutaneous melanoma as well as nmscs (ibid).3 it is thought that eumelanin protects against melanoma promoting nutrient photolyases (e.g. folate).28 in this respect, identical uvr exposure may result in vastly disparate realized doses of uvr and differential degrees of noisome exposure. other such examples include the case of atypical nevi, also known as a dysplastic nevus (dn). uvr contribution to cutaneous melanoma can also be explained by its role in the genesis of dysplastic nevi, or clark nevi. the dysplastic nevus is a term coined by clark and his colleagues in 1978, initially referred to as b-k syndrome (eponymously inspired by families observed with morphological characteristics associated with dysplastic nevus syndrome).50 dn is a complex and fraught subject in the field of dermatology. dns are considered technical precursors to cutaneous melanoma due to their striking similarity to cutaneous melanoma in cytologic and histologic appearance.51 dns are highly associated with cutaneous melanoma. it is estimated that the rr conferred by the presence of more than 5 atypical nevi ranges from 6.112.4.41 yet, dns have a remarkably low conversion rate to cms. current findings suggest that conversion rate of dn in men is 0.03% and 0.009% in women.41 conversely, it is estimated that ~20% of melanomas begin as dns.41 uvr is pointed to as a distinct factor that is sufficient, but not necessary to the de novo genesis of dns.52 the molecular dialogue amongst genetic and environmental constituent factors contributes to the complexity surrounding precise attribution of uvr to the induction of cutaneous melanoma. hormones & cutaneous melanoma cutaneous melanoma risk and hormonal supplementation, especially as it relates to oral contraceptives (ocs) and hormone replacement therapy (hrt), is a contentious subject in modern literature, with a variety of studies reporting contradictory findings. initial findings presented by ellerbroek (1968) and beral (1977) separately reported that history and oc use were associated with increased risk of other exogenous factors skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 206 cutaneous melanoma.53,54 in addition, epidemiologic data has consistently reported increased incidence of cutaneous melanoma in women, but not men, 25-29 years of age.55,56 it was suspected that ocs were significant explanatory factors. a large-scale review of the subject was subsequently undertaken by hannaford, mackintosh, et al. (1991) leveraging data derived from the royal college of general practitioners and the oxford family planning association. amassing over 23,000 subjects, the institutions reported no clinically significant association between rr of cutaneous melanoma and use, history, or duration of oral contraceptive use.57 the royal college of practitioners’ study did report an increased risk of cutaneous melanoma associated with ocs, however, that finding failed to achieve statistical significance.57 the report by the rcp criticized previous findings, indicating that sample sizes were insufficient and uv exposure remained poorly controlled, acting as a potential confounder. in the last several decades, research pertaining to the use and impact of ocs on incidence of cutaneous melanoma has been the subject of routine debate.58 the preponderance of studies indicate that while ocs are typically associated with cutaneous melanoma, that relationship is weak and is mitigated when proper controls are integrated.59,60 adjusting for uvr exposure and phenotypic risk factors depresses reported associations. cervenka and saleh et al. reviewed data gathered from a french cohort comprising 79,365 women from 1992-2008, reporting that oc use was not strongly associated with cutaneous melanoma.61 results of the cohort study suggest that oc use, strength, and duration increase rr for cutaneous melanoma, but that risk fails to achieve statistical significance once the researchers controlled for uvr. the team concludes that there exists little evidence linking oc use to increased incidence of cutaneous melanoma. rather, increased associations may be explained by intentional uvr exposure amongst oc users. a subsequent analysis by cervenka, al rahmoun, mahamat-saleh et al. replicated prior findings, with the exception that the team reported a “border-line” positively significant relationship between oc use and melanoma, with a linear increase associated with duration of oc use.62 the team reaffirms that there exists no strong evidence linking hormonal supplementation to cutaneous melanoma.62 additional large scale inquiries into the matter have produced concordant findings.56 a notable, recent exception was documented by koomen, joose, et al. reporting that oc use, dosage, and duration of oc use was strongly associated with cutaneous melanoma incidence.63 results of this study may be considered limited as a result of insufficient data regarding confounds, particularly uvr exposure amongst reported subjects. findings regarding the impact of hormonal replacement therapies (hrts) on the incidence and induction of cutaneous melanoma report similar findings.59 hrts do not appear to be strongly implicated in the induction of cutaneous melanoma.64 hrt refers to supplementation, typically of oestrogen and progestin, in target groups following menopause. hrts were implicated in the induction of cutaneous melanoma following inquiry into the supposed link between ocs and cutaneous melanoma. associations appear to be tenuous and significant associations are typically achieved when stratifying populations by age (e.g. 30-40 ya), oc duration (e.g. x > 10 years), and marked sun exposure.65,66 gandini, iodice, et al. summarize data in a large-scale review encompassing 36 skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 207 observational studies and 5626 confirmed cases of cutaneous melanoma.59 the group report that hrts (in addition to ocs) were not significantly associated with cutaneous melanoma risk.59 however, age at first birth appeared to be a significant risk factor for cutaneous melanoma. various reviews have arrived at similar conclusions.59,67, one exception lies in a review by botteri, stoer, et al. which assesses the impact of cutaneous melanoma risk conferred by hrts. the authors conclude that there exists a significant, positive relationship between hrt and cutaneous melanoma (rr = 1.44).68 the authors caution that estrogen and progestin may exhibit disparate, competing effects.68 the latter may serve as a protective factor in the pathogenesis of cutaneous melanoma.69,70 while the study estimates the impact of uva on a norwegian cohort, their estimates for exposure depend on an estimate for uva exposure according to spatial location. thus, confounds for increased exposure among hrt users presents a salient limitation. it should be noted that other explorations into the matter have reported contrary findings, suggesting that the effects born of hrt supplementation do not differ by selected hormone type.71 in a recent review of epidemiologic data from a large european cohort, cervenka, al rahmoun, mahamatsaleh et al. document a nonsignificant increase in or associated with cutaneous melanoma incidence.62 while modern findings point away from a direct, or rather agnostic link between oc use hrt and cutaneous melanoma incidence, the potential role for hormones in the pathogenesis of cutaneous melanoma remains conceivable. for example, animal experiments provide evidence to support the role of estrogen in the proliferation of melanocytes and the production of melanin.72 it may be of clinical interest, too, that periods of hormonal saturation (e.g. pregnancy) are associated with various topical manifestations of melanocyte activity including but not limited to changes in size and relative frequency of naevi, formation of the linea nigra and appearance of acute melasma in pregnant subjects.73,74 several studies investigating the effect of pregnancy on cutaneous melanoma mortality have concluded that melanoma prognosis does not significantly differ between pregnant and non-pregnant controls.75,76 however, the age at first and last birth have been linked to incidence of cutaneous melanoma, as has the number of offspring.59,77 a recent metaanalysis conducted by li, gu, and cen (2015) assessing the relationship between cutaneous melanoma and age at birth, documented an increased risk associated with age at first birth (pooled rr = 1.44) and declining risk with respect to number of offspring (x >1).67 upon meta-analysis, subjects reporting advanced age at first birth were subject to increased cutaneous melanoma risk, as were those with later ages at first birth.67 the authors caution that such an association is contestable and has not been universally replicated.67 yet, cutaneous melanoma response to hormonal fluctuation is complicated by the finding that estrogen receptor positive patients do not respond to antiestrogens or oophorectomy; in contrast, nearly 67% of estrogen-receptor positive breast cancer patients respond to identical treatments.78 such findings invite further research into the precise mechanisms implicated in the interplay between hormonal fluctuation and cutaneous melanoma. potential areas for exploration may target the differential effects exerted by different dermal subtypes of estrogen receptors in cutaneous melanoma prognosis.79 for example, estrogen-receptor beta (𝜺rb) concentrations in the tumor skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 208 microenvironment were predictive of prognosis.80 higher relative 𝜺rb concentrations were associated with decreased tumor proliferation and were inversely related to breslow depth.81 on the other hand, its sister receptor, estrogenreceptor alpha (𝜺ra), was positively associated with proliferative activity.79 such findings may be explanatory in mortality specific discrepancies between male and female subjects at nearly all stages of cutaneous melanoma prognosis. more intriguing is marked differences in survival rates between postand pre-menopausal subjects, the latter being associated with improved prognosis.56 other areas for clinical exploration may involve interactions between circulating hormones and solar radiation. while controlling for uvr exposure reduced associations reported between cutaneous melanoma incidence in subjects taking ocs and hrts, it could be the case that uvr and estrogen exert interactive effects that magnify relative risk of cutaneous melanoma incidence. it is beyond the scope of this paper to evaluate the veracity of these claims. dietary factors, obesity, smoking & vitamins dietary risk factors implicated in the induction of cutaneous melanoma are seldom identified in present literature. exogenous cases of cutaneous melanoma linked to dietary factors do not appear pronounced at present. the dearth of available evidence may be the result of faulty design, poor controls, or a want of inquiry into the matter. a notable exception to this finding is reported alcohol consumption. consumption of ethanol related beverages is associated with significant increases in cutaneous melanoma risk.82-84 relevant associations between alcohol and cutaneous melanoma risk are documented within multiple analyses in the last several decades. william et al. (1977), holman et al. (1986), stryker et al. (1990), millen et al. (2004), and rivera et al (2016), document significant associations between alcohol consumption and cutaneous melanoma risk.82,84-87 or risk estimates vary considerably with holman reporting a or value of ~2 associated with 4 or more drinks per week, while millen generate or estimates of 1.65 associated with 1.4 drinks per week, and rivera et al. report or associated with alcohol intake of 1.4 for those in the highest quintiles of consumption (x > 20 units of alcohol per day).82,84,86 it should be noted that several studies have also failed to replicate findings demonstrating a link between alcohol consumption and melanoma risk.88,89 thus, there appears to be a probable but not definitive link between alcohol consumption and cutaneous melanoma. the mechanisms underlying increased cutaneous melanoma risk are typically ascribed to dna adducts as a result of acetaldehyde formation, ros species generation, inflammatory factors, and epigenetic interactions with respect to histone methylation and acetylation.82,90,91 a more in-depth analysis of the specific pathways involved in cutaneous melanoma induction resultant from ethanol intake were described by rivera et al. (2016).82 leveraging meta-data from a three-cohort study, the team find evidence of an increased risk of cutaneous melanoma following ethanol consumption, reporting pooled-risk of 1.14 for all groups.82 the authors remark that the melanomagenic properties attributed to alcohol derive from acetaldehyde induced dna adducts and potential photosensitization mechanisms.82 skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 209 in accordance with these findings, the authors suggest that greater risk conferred to females, as opposed to males, of cutaneous melanoma risk attributable to alcohol consumption is the result of greater effective concentrations of acetaldehyde reaching melanocytes in female subjects.82 additionally, forms of ethanol containing higher effective doses of acetyl-aldehydes were more strongly associated with melanoma risk (e.g. white wine).82 an interesting feature of the team’s study observed that incidence of melanoma in-situ was strongly correlated with alcohol consumption on non-sun exposed sites, as opposed to only modest associations reported in sun-exposed sites.82 acetaldehyde penetration of melanocytes and its secondary genotoxic effects seems a potential candidates for exploration. obesity, more generally excess bmi, is cited as a risk factor in a number of carcinomas.92 evidence establishing a connection between cutaneous melanoma and obesity is scant. for instance, one of the few notable studies to explore this question was undertaken by sergentanis et al. (2013).93 the team reports that excess bmi is a significant risk factor for cutaneous melanoma (pooled or=1.31) in males but not females.93 the researchers cautioned that while no significant association was found among females with gratuitous bmi, it still may be a relevant factor for consideration.93 it may be of clinical interest that patients with excess bmi, notably males, tend to have a better prognosis once diagnosed with melanoma, and other cancers more generally.94 obesity, especially in males, is linked to higher levels of ambient estrogen.95 the obesity paradox (op) may hark back to an earlier discussion of the role played by estrogen in the suppression of tumorigenesis and proliferation in cutaneous melanoma via 𝜺rb concentrations. smoking, almost by definition, is linked to a spate of highly lethal carcinomas.96 evidence linking smoking to cutaneous melanoma is absent, with separate analyses failing to report significant associations.97-99 in fact, case control studies identified report insignificant, but inverse, associations between smoking and cutaneous melanoma risk.100 there is some discussion that smoking may, surprisingly, act as a protective factor in the induction of cutaneous melanoma.96 while this paper does not focus on protective exogenous factors connected to cutaneous melanoma risk, we note that there exists ample evidence linking waning cutaneous melanoma risk to higher serum levels of carotenoids (e.g. beta-carotene), flavonoids, polyphenols, alpha-tocopherol (vitamin e), retinol (vitamin a), resveratrol, pomegranate extract, and regular coffee consumption.101-105 the effects born of the aforementioned supplements are numerous and manifold, but include reparation of uvr induced damage, regulation of apoptosis, decreased proliferation, and enhanced differentiation.106 cutaneous melanoma patients reporting higher serum concentrations of vitamin d, in particular, were reported to have a superior prognosis following diagnosis, especially in metastatic subjects.107.108 those subjects that routinely consumed coffee enjoyed reductions in cutaneous melanoma risk (or = 0.75).109-111 in a large prospective cohort (n = 69,635), vitamin a (retinol) appeared to exert a significant chemopreventive benefit in subjects reporting current oral supplementation. it should be noted that upon analysis of the relevant literature, the authors note that such findings accord with some but not all current findings.112 in a meta-analysis of supplementation findings related to melanoma induction, russo et al. document chemopreventive benefits skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 210 associated with vitamin e (alphatocopherol), vitamin d (cholecalciferol), vitamin-c (ascorbic acid), and vitamin k (potassium).108 dietary factors implicated in the induction of cutaneous melanoma are limited and typically involve alcohol consumption. smoking and obesity were considered as potential risk factors. obesity remains a plausible candidate for exogenous risk, while smoking does not appear strongly correlated with cutaneous melanoma. it should be mentioned that the above factors, while prominent, confer markedly lower risk for cutaneous melanoma in comparison with traditional risk factors such as uvr. ionizing radiation (x = 125nm) incidence of cutaneous melanoma as a result of ionizing radiation is another topic bereft of broad exposure in current research. while ionizing radiation is a well-established mutagen, its role in the induction of cutaneous melanoma is dubious. it is known that shorter wavelengths (e.g. x < 280; e.g. uvc (200-280nm)) can induce cutaneous melanoma in bombarded subjects.113 cohort analyses of ionizing-radiation related occupations evidence increased risk of cutaneous melanoma.113 we examine data concerning the effect of ionizing radiation on melanomagenesis provided by four relevant working papers. one of the first reports linking to cutaneous melanoma to ionizing radiation was observed by donald austin & reynolds (1994).114 the duo, in response to an outsized incidence of melanoma cases (four-fold incidence in comparison with average population) at the lawrence livermore national laboratory in alameda county, engaged in a study which sought to determine if chronic exposure to ionizing radiation was sufficient to explain this outcome.114 multivariate analysis revealed significant risk (or = 3.0) for cutaneous melanoma associated with ionizing radiation.114 the authors note that while chance may explain this finding, it is doubtful.114 their conclusion stems from the following factors: “incidence was disproportionately greater amongst laboratory workers than would be expected in standard population models”; the data accord with previous findings by pion et al. (1995), mantanoski & seltser et al. (1975), caldwell & kelly et al. (1983), hadjimichael & ostfeld et al. (1983), wright & peters (1983); “stratifying by specific occupation” (e.g. chemist) and even “ever/never” radiation exposure significantly increased cutaneous melanoma risk, among other factors.114 intriguingly, the duo add nuance to their discussion, adding that the absence of measurable dose-response findings in tandem with “other identified occupational risk factors” support the hypothesis that high single dose cases of ionizing radiation may be explanatory.114 in response to concerns voiced by austin & reynolds, fink & bates (2005) would conduct an epidemiological review to assess incidence of melanoma among several groups –– “(1) the canadian radiation dose registry, (2) nuclear industry workers, (3) subjects near nuclear test blasts, (4) survivors of the atomic bombings of japan, (5) airline pilots and cabin attendants, (6) recipients of medical radiation, and (7) radiological technicians.”115 the researchers report that subjects that were more likely to develop leukemia related to radiation exposure appeared to be similarly at risk for melanoma.115 the authors caution that there could exist unexplored confounds, such as uvr exposure. in its absence, however, a causal relationship is possible, thereby skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 211 adding credence to the hypothesis propounded by austin & reynolds.114 later reviews evidence the role of ionizing radiation in the pathogenesis of cutaneous melanoma. friedman, sigurdson, et al. (2003) document increased risk of melanomagenesis among radiation technicians/radiation related workers exposed to low, chronic levels of ionizing radiation, especially those practicing before 1950 and those who opted against protective materials.106 the report surveyed 68,588 radiologic technicians, all caucasian and ~70% female. the authors note that other studies evaluating the relationship tend to rely on fatality rates. such studies, they caution, may lead to underreporting associations among certain low-fatality diseases (e.g. melanoma).116 conversely, in a more recent review, azizova, bannikova, and grigoryeva (2018) survey 22,377 individuals, finding that cutaneous melanoma risk is not modified by exposure to ionizing radiation.117 the cohort is comprised of russian nuclear production facility personnel and mayak production association personnel from 1948–1982. the cohort was tracked until the end of 2013. the authors observe that the incidence of non-melanoma skin cancer (nmsc) is significantly associated with cumulative gamma ray exposure greater than 2.0 sv (2000 msv). no such association was found with cutaneous melanoma.117 the mechanisms by which ionizing radiation exerts differential effects with respect to nmsc and cutaneous melanoma presents an avenue for future exploration. few papers focus on the link between ionizing radiation and melanoma. most are epidemiologic. none –– that can be found – – can prove causality, nor do they explore the molecular pathways proposed as explanatory. it is possible that ionizing radiation is associated with melanoma, however, the precise cascade initiated by ionizing radiation in the induction of cutaneous melanoma remains unresolved. chemicals & pollution the link between exposure to various chemicals and pollutants and the pathogenesis of cutaneous melanoma is well-documented in modern literature. the trove of synthetic contributors to cutaneous melanoma induction include, but are not limited to: polycyclic achromatic hydrocarbons (pahs), polychlorinated biphenyls (pcbs), polyvinyl chlorides (pvcs), levodopa (l-dopa), heavy-metals (e.g. nickel, lead), asbestos, localized trauma (e.g scar-tissue), volatile organic compounds (vocs, e.g. benzene), insecticides (e.g. carbaryl, parathion, & toxaphene), and fungicides (e.g. maneb). evidence establishing the connection between the above exposure-types and cutaneous melanoma derives from animal models, occupational cohort studies, and meta-analyses.78 theories which attempt to explain chemical/pollutant induced cutaneous melanoma are varied. primary explanations include the melanin-affiliated hypothesis of mutagenesis. larsson (1993) reports that it is known that melanin exhibits strong binding affinities for percutaneously leached substances, especially organic amines and metal ions.118 as a result, local concentrations of various chemicals/pollutants aggregate in melanocytes leading to eventual histologic abnormalities after cumulative exposure.118 more specific explanations are reported by rockley et al. (1994) who suggest that chemical induction of cutaneous melanoma can be attributed to: (1) the binding of chemical/pollutants to keranocytic dna and additional macromolecules; (2) promotion of skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 212 “cytochrome p-450 activities;” (3) activation of protein kinase –c, which the authors note lead to “deregulation of cellular growth and differentiation”.78 alternative routes of chemical/pollution related cutaneous melanoma induction are thought to arise from systemic reductions in cellular immunity.78 we will review several associations most prominent in the literature. pahs present a powerful driver of chemicalrelated cutaneous melanoma induction. pahs are pyrolytic by-products typically found in tar, oil-products, soot, anthracene, pitch, and creosote.78 specific pah derivatives tied to cutaneous melanoma induction include 7,12-dimethylbenz-(a)anthracene (dmba), 5,9,10-trimethyl-l, 2benzanthracene, and coal tar derivatives.119 rockley et al. relay findings reported by edgecomb & mitchelich (1963) and della & report (1956) documenting nevus proliferation and cutaneous melanoma linked to application of dmba in animal models.78 occupational exposures to pahs are associated with a significantly increased risk of cutaneous melanoma.120 in a largescale meta-analysis of cutaneous melanoma incidence among oil-refinery workers, mehlman (2006) reports significant risks attributed to oil-refinery occupation (or = 1.16.7).121 pahs are prominent pollutants present in petrochemical refineries. when stratified by occupation (i.e. exposure to pahs, pcbs, benzene, asbestos & heavy oils) or risk values rise.121 the author notes that there exist disparate findings between industry sponsored studies and independent reviews, with the former reporting negative results. it is probable that negative findings are the result of industry bias.121 occupational analysis of cutaneous melanoma incidence amongst fireman report increased cutaneous melanoma risk (or = 1.21).122 the authors write that increased cutaneous melanoma risk may be resultant from excess pahs, arsenic, among other carcinogenic substances that penetrate personal protective equipment (ppe).122 while it is difficult to prove –– without confound –– the effects ascribed to pahs in occupational cohorts, their role in the pathogenesis of cutaneous melanoma appears likely. pcbs have been similarly implicated in the induction of cutaneous melanoma. pcbs are found in coolants, manufacture of capacitors, pollutants in certain water supply systems, fire retardants, hydraulic fluids, cutting oils and as plasticizers in paints, cements, stabilizing additives in pvcs, among others.78 pcbs are a unique risk factor for cutaneous melanoma. for instance, plasma concentrations of pcb are associated –– in dose dependent fashion –– with cutaneous melanoma risk. subjects found with the highest serum concentrations of pcb were found to have significantly increased risk compared with controls (or = 6.02 (dioxin pcb ) – 7.02 (non-dioxin pcb)).123 bahn et al. reports increased cutaneous melanoma incidence among petrochemical workers exposed to greater concentrations of pcb.124 brown & jones (1981) failed to find an increased risk of cutaneous melanoma mortality associated with low-levels of pcb exposure.125 in a systematic review and meta-analysis conducted by zani, ceretti, et al. (2017) pcb exposure was associated with higher standardized mortality incidence ratios (pooled smr = 1.32).126 however, the authors conclude that there is not strong evidence to suggest that pcbs are implicated in the induction of cutaneous melanoma, although it is a risk factor.126 taken together, the assortment of both negative and positive findings suggests that pcb related cutaneous melanoma induction is dependent on realized dose. skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 213 studies examining the role of fungicides and insecticides in cutaneous melanoma induction find likely associations.127 the fungicide, maneb (polymeric dithiocarbamate), was implicated as a risk factor for cutaneous melanoma induction by dennis & lynch et al. (2010) in a review of pesticide applicators in the agricultural health study.128 exposure to maneb was found to increase cutaneous melanoma risk in a dose dependent manner ((63 > x à or = 1.6); (x > 63 or = 2.4)).128 insecticides documented to be linked to cutaneous melanoma risk include toxaphene (insecticide organochlorine) (rr = 0.7-2.9), parathion (insecticide organothiophosphate) (or = 1.6-2.4), and carbaryl (insecticide carbamate) (or = 1.3-1.7). 127,128 other chemicals and pollutants that have been reportedly associated with c cutaneous melanoma increase include asbestos, pvcs, arsenic, l-dopa, hydrocarbon solvents (e.g. formaldehyde) among others. each factor is uniquely associated with cutaneous melanoma and is potentially causally linked to its induction. rockley et al. (1994) document the gamut of associations attributed to the aforementioned factors in an extensive meta-review. their work is compendious and should be revisited for further reference.78 in summary, a variety of exogenous chemicals and pollutants are probable agents in the exogenous induction of cutaneous melanoma. while this review specifically addressed pahs, pcbs, maneb, toxaphene, carbaryl, and parathion there exist a panoply of other candidates for consideration that may, too, play a role in melanomagenesis. this review has sought to identify and examine the various exogenous factors linked to cutaneous melanoma induction. the identification of potentially exogenous sources of cutaneous melanoma induction is crucial to the prevention of future cutaneous melanoma cases. while uvr is a permanent fixture of exogenous research into the induction of melanoma, this review endeavors to present additional candidates for consideration, explore their implications, and challenge prevailing attitudes regarding the attribution of cutaneous melanoma incidence to a particular exogenous source. what manifests is a broad and sweeping array of incident factors spanning uva/uvb, hormonal supplementation, dietary and lifestyle related factors, ionizing radiation, chemicals and pollutants. conflict of interest disclosures: none funding: none corresponding author: lawrence s. moy, md 1101 n sepulveda blvd #100 manhattan beach, ca 90266 phone: 310-546-7780 fax: 310-546-2440 email: lsm.doc@me.com references: 1. refs us department of health and human services. the surgeon general's call to action to prevent skin cancer. washington (dc): office of the surgeon general (us); 2014. available from: https://www.ncbi.nlm.nih.gov/books/nbk247172/ 2. iarc working group on the evaluation of carcinogenic risk to humans. 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(2010). pesticide use and cutaneous melanoma in pesticide applicators in the agricultural heath study. environmental health perspectives, 118(6), 812–817. https://doi.org/10.1289/ehp.0901518 powerpoint presentation 0 20 40 60 80 10 0 5657 60 5556 63 404042 r e s p o n d e rs , % worst weekly pruritus nrs ≤3 0 20 40 60 80 10 0 7172 75 70 73 81 5657 61 r e s p o n d e rs , % dlqi ≤5 materials and methods patients and treatment • in ecztend, patients who completed pt of tralokinumab received open-label tralokinumab 300 mg every two weeks (q2w, home use) after a 600 mg loading dose plus optional topical corticosteroids (us class ≥4 or europe class ≤3) or topical calcineurin inhibitor, with visits every 8 weeks o all patients who completed pt at sites with ecztend were eligible to enroll in ecztend, regardless of prior treatment or response o for key inclusion and exclusion criteria, please see blauvelt et al3 • adult patients included in this post hoc analysis completed 56 weeks of open-label tralokinumab treatment in ecztend by the data cutoff (april 30, 2021) (figure 1a) • patients self-reported race at baseline of ecztend (figure 1b) • proportion of patients achieving easi-75/90, iga 0/1, easi≤7, worst weekly pruritus nrs≤ 3, and dlqi ≤ 5 were assessed. easi-75/90 determined relative to pt baseline • data are presented as observed. intermittent missing data are presented using last observation carried forward (locf). modified non-responder imputation (mnri) sets discontinuation from ecztend due to adverse event(s) or lack of efficacy as non-response and uses locf for other missing data • to account for potential baseline confounders with racial subgroup, logistic regression analysis adjusting for country, weight, easi, ethnicity and age (all at ecztend baseline) in addition to racial subgroup were conducted. estimated proportions from these analyses were expressed relative to us non-hispanic patients • data were used as per food and drug administration (fda) label and united states prescribing information (uspi) analyses asian n=203 black n=108 white n=1081 mean age, y (sd) 37.9 (13.9) 39.6 (13.4) 39.4 (14.1) male, n (%) 125 (61.6) 45 (41.7) 637 (58.9) ethnicity, n (%) hispanic or latino not hispanic or latino 2 (1.0) 201 (99.0) 5 (4.6) 103 (95.4) 79 (7.3) 1002 (92.7) country, n (%) united states, 49 (24.1) canada, 55 (27.1) germany, 2 (1.0) great britain, 9 (4.4) spain, 1 (0.5) france, 1 (0.5) japan, 86 (42.4) united states, 94 (87.0) canada, 7 (6.5) germany, 3 (2.8) great britain, 3 (2.8) france, 1 (0.9) united states, 187 (17.3) canada, 137 (12.7) poland, 178 (16.5) germany, 246 (22.8) great britain, 52 (4.8) spain, 123 (11.4) belgium, 62 (5.7) france, 61 (5.6) italy, 15 (1.4) czech republic, 20 (1.9) baseline scores parent trial ecztend parent trial ecztend parent trial ecztend iga, n (%) 3 4 89 (43.8) 114 (56.2) 51 (25.1) 14 (6.9) 73 (67.6) 35 (32.4) 22 (20.4) 7 (6.5) 575 (53.2) 506 (46.8) 308 (28.5) 63 (5.8) mean easi (sd) 32.5 (14.5) 9.2 (11.7) 27.9 (12.0) 6.9 (11.0) 30.7 (12.7) 8.6 (10.0) mean scorad score (sd) 70.0 (13.5) 33.5 (18.5) 65.3 (12.4) 27.6 (18.6) 69.2 (12.7) 33.5 (19.1) mean poem (sd), n 22.6 (4.7), 199 13.2 (6.8), 197 20.4 (6.2), 99 10.6 (7.2), 106 22.3 (5.1), 1037 12.4 (7.4), 1048 mean dlqi (sd), n 16.4 (6.9), 200 6.9 (5.8), 197 16.0 (7.7), 100 6.9 (6.4), 106 16.6 (6.9), 1041 6.7 (6.0), 1048 mean worst pruritus nrs (sd), n 7.9 (1.3), 180 5.3 (2.5), 202 8.0 (1.8), 63 4.6 (2.9) 7.6 (1.5), 971 4.9 (2.7), 1080 mean sleep interference nrs (sd), n 7.2 (1.9), 180 3.6 (2.8), 202 7.4 (2.2), 63 3.0 (3.1) 6.8 (2.0), 971 3.1 (2.8), 1080 efficacy and safety of up to two years of tralokinumab treatment in adults of different racial subgroups with moderate-to-severe atopic dermatitis tiffany mayo1, april armstrong2, leon kircik3, jonathan i. silverberg4, andrew blauvelt5, ben esdaile6, shannon schneider7, thomas mark8, melinda gooderham9, andrew f. alexis10 1university of alabama at birmingham, birmingham, al, usa; 2keck school of medicine of university of southern california, los angeles, ca, usa;3icahn school of medicine at mount sinai, new york, ny, usa; 4the george washington school of medicine and health sciences, washington, dc, usa; 5oregon medical research center, portland, or, usa; 6whittington health national health service foundation trust, london, uk; 7leo pharma inc., madison, nj, usa; 8leo pharma a/s, ballerup, denmark; 9skin centre for dermatology, peterborough, on, canada; 10weill cornell medicine, new york, ny, usa table 1. baseline demographic and disease characteristics of patients by racial subgroup table 2. summary of aes in ecztend by racial subgroup ain pts, worst pruritus nrs was assessed daily; in ecztend, worst pruritus nrs was assessed based on recall of the previous week before the visit. conclusions • improvements in disease severity, itch, and quality of life were comparable across different racial subgroups following up to two years of tralokinumab treatment in adults with moderate-to-severe ad • limitations of this analysis include the lack of a placebo arm in ecztend, disparate sample sizes across racial subgroups, and possible confounders not considered • the lower response rates observed for the asian subgroup relative to other racial subgroups could be partially explained by adjusting for country figure 1. schematic of (a) ecztend interim analysis of adult patients and (b) patient disposition at parent trial completion, ecztend baseline, and at april 30, 2021 data cutoff objective to evaluate the efficacy and safety of up to 2 years of tralokinumab treatment by self-identified racial subgroup (asian, black, white) in adults with moderate-to-severe ad results patients, demographics, and clinical characteristics • this post hoc analysis included 1392 adult patients who had completed 56 weeks of tralokinumab in ecztend (up to 2 years total) at data cutoff, april 30, 2021 and self-reported their race as asian, black, or white (figure 1b, table 1) o among patients who had completed 56 weeks of tralokinumab in ecztend at data cutoff, 24% had skin of color (self-reported race as asian, black, or other) o very few patients self-reported their race as other than asian, black, or white (n=38 patients total) and therefore were not included in this analysis • baseline demographic and disease characteristics were largely balanced across subgroups (table 1), although regional differences were present figure 2. proportion of patients by racial subgroup achieving easi-75, easi-90, iga 0/1, and easi≤7 at week 56 of ecztend references 1. weidinger s, novak n. lancet. 2016;387(10023):1109-1122. 2. kaufman b, et al. exp dermatol 2018; 27: 340-357. 3. blauvelt a, et al. j am acad dermatol. 2022;s0190-9622(22)02345-3. disclosures tiffany mayo has served as an investigator or consultant for eli lilly, chemocentryx, pfizer, janssen, galderma, bristol myers squibb, acelyrin, novartis, leo pharma, arcutis, and procter and gamble. april armstrong has served as a research investigator and/or scientific advisor to abbvie, almirall, arcutis, aslan, beiersdorf, bi, bms, epi, incyte, leo, ucb, janssen, lilly, nimbus, novartis, ortho dermatologics, sun, dermavant, dermira, sanofi, regeneron, pfizer, and modmed. leon kircik has served either as an investigator, consultant, or speaker for abbvie, almirall, amgen, arcutis, bausch health canada, bristol myers squibb, boehringer ingelheim, cellceutix, celgene, coherus, dermavant, dermira, eli lilly, leo, mc2, maruho, novartis, ortho dermatologics, pfizer, dr reddy's laboratories, sun pharma, ucb, taro, and xenoport. jonathan i silverberg reports honoraria as a consultant/advisory board member from leo pharma and has acted as a consultant for and/or received grants/honoraria from abbvie, anaptysbio, asana biosciences, galderma research and development, gsk, glenmark, kiniksa, leo pharma, lilly, medimmune, menlo therapeutics, pfizer, puricore, regeneron, and sanofi. andrew blauvelt has served as a speaker (received honoraria) for abbvie, arcutis, bristol-myers squibb, eli lilly and company, pfizer, regeneron, sanofi, and ucb, served as a scientific adviser (received honoraria) for abbvie, abcentra, affibody, aligos, almirall, alumis, amgen, anaptysbio, arcutis, arena, aslan, athenex, bluefin biomedicine, boehringer ingelheim, bristol-myers squibb, cara therapeutics, dermavant, ecor1, eli lilly and company, escient, evelo, evommune, forte, galderma, highlightii pharma, incyte, innoventbio, janssen, landos, leo, merck, novartis, pfizer, rapt, regeneron, sanofi genzyme, spherix global insights, sun pharma, tll pharmaceutical, trialspark, ucb pharma, vibliome, and xencor, and has acted as a clinical study investigator (institution has received clinical study funds) for abbvie, acelyrin, almirall, amgen, arcutis, athenex, boehringer ingelheim, bristol-myers squibb, concert, dermavant, eli lilly and company, evelo, evommune, galderma, incyte, janssen, leo, merck, novartis, pfizer, regeneron, sun pharma, and ucb pharma. ben esdaile has served either as an investigator, advisor or speaker for leo pharma, l’oréal, thornton & ross, bioderma, skin + me and abbvie. shannon schneider and thomas mark are employees of leo pharma. thomas mark owns leo pharma stock. melinda gooderham has been an investigator, speaker and/or advisor for: abbvie, amgen, akros, anaptysbio, aslan, arcutis, aristea, bausch health, bms, boehringer ingelheim, celgene, dermira, dermavant, eli lilly, galderma, gsk, incyte, janssen, kyowa kirin, leo pharma, medimmune, merck, meiji, moonlake, nimbus, novartis, pfizer, reistone, regeneron, roche, sanofi genzyme, sun pharma, and ucb. andrew f. alexis has received grants (funds to institution) from leo pharma, novartis, almirall, bristol myers squibb, amgen, vyne, galderma, valeant (bausch health), cara, arcutis, dermavant, abbvie, and castle; has served as an advisory board member or consultant for leo pharma, galderma, pfizer, sanofi-regeneron, dermavant, beiersdorf, ortho, l’oreal, bms, bausch health , ucb, vyne , arcutis, janssen, allergan, almirall, abbvie, sol-gel , amgen, visualdx, eli lilly, swiss american, and cutera; and a speaker for regeneron, sanofi-genzyme, pfizer, and bristol myers squibb. acknowledgements this analysis was sponsored by leo pharma a/s. medical writing according and editorial support from alphabet health by clair geary, phd was funded leo pharma a/s, ballerup, denmark, to good publication practice guidelines (https://www.ismpp.org/gpp3). this poster is an encore of a previous presentation at the fall clinical dermatology conference, oct 20 – 23, 2022. introduction • atopic dermatitis (ad) is a chronic skin disease which may impact patients throughout their lifespan, requiring efficacious long-term treatment options with a favorable safety profile1 • although ad is highly prevalent in patients with skin of color, data on the efficacy of ad therapies in these patients is limited since most clinical trials enroll predominately white patients2 o several standard measures, including easi, can underestimate ad severity in dark skin2 • tralokinumab, a specific, high-affinity interleukin-13 inhibitor, is approved in europe, canada, and the united states for the treatment of adults with moderate-to-severe ad • ecztend (nct03587805) is an ongoing open-label extension trial assessing the safety and efficacy of tralokinumab over 5 years after the completion of parent trials (pt) the safety profile of up to 2 years of tralokinumab treatment was consistent across racial subgroups • through week 56 in ecztend, rates of adverse events (aes), serious aes, and aes leading to drug withdrawal were comparably low across racial subgroups (table 2) • the majority of aes in all subgroups were mild or moderate in severity and subjects recovered from most of the aes figure 3. percentage of patients achieving worst weekly pruritus nrs ≤3 and dlqi ≤5 by racial subgroup at week 56 of ecztend adjusting for differences in baseline characteristics and country between subgroups impacts estimated responder proportions • adjusted for race and country as main effects, easi-75 was achieved in 88% of asian patients, 90% of black patients, and 90% of white patients (figure 4) • similar patterns of estimated response were observed for iga 0/1 (figure 4) and when adjusting for region as main effect or the interaction between region and race figure 4. percentage of patients achieving easi-75 and iga 0/1 by racial subgroup before and after adjusting for baseline differences asian (n=203; pye=386.2) black (n=108; pye=169.7) white (n=1081; pye=1808.0) n (%) rate (ne/100 pye) n (%) rate (ne/100 pye) n (%) rate (ne/100 pye) all aes 162 (79.8) 167.8 71 (65.7) 142.6 850 (78.6) 208.2 severity mild 143 (70.4) 130.2 57 (52.8) 101.9 717 (66.3) 134.1 moderate 67 (33.0) 34.7 35 (32.4) 35.3 503 (46.5) 66.8 severe 10 (4.9) 2.8 7 (6.5) 5.3 80 (7.4) 7.4 serious aes 12 (5.9) 3.4 7 (6.5) 4.7 81 (7.5) 5.4 leading to withdrawal from trial 2 (1.0) 0.5 2 (1.9) 1.2 30 (2.8) 1.7 outcome not recovered/ not resolved 68 (33.5) 28.0 23 (21.3) 24.2 269 (24.9) 23.7 recovering/resolving 18 (8.9) 5.4 12 (11.1) 10.0 153 (14.2) 12.2 recovered/resolved 151 (74.4) 133.1 65 (57.4) 106.0 799 (73.9) 169.2 recovered/resolved with sequelae 1 (0.5) 0.3 3 (2.8) 1.8 16 (1.5) 1.0 unknown 3 (1.5) 1.0 1 (1.0) 0.6 28 (2.6) 1.9 scan to download a copy of this poster copies of this poster and its content, obtained through this qr code, are for personal use only and may not be reproduced without written permission from the authors abbreviations adj., adjusted; ae, adverse event; ad, atopic dermatitis; dlqi, dermatology life quality index; e, number of adverse events; easi, eczema area and severity index; iga, investigator’s global assessment; locf, last observation carried forward; mnri, modified non-responder imputation; n, number of patients achieving the indicated metric, or with ≥1 event; ne, number of events; n, number of patients with recorded observation; nrs, numerical rating scale; pye, patient-years of exposure; pt, parent trial; q2w, every 2 weeks; sd, standard deviation comparable efficacy across racial subgroups with up to two years of tralokinumab treatment o worst weekly pruritus nrs ≤3 was achieved in 42% (71/169) of asian patients, 63% (48/76) of black patients, and 60% (458/765) of white patients, as observed (figure 3) o similar patterns of response were observed for easi-90, easi ≤7, iga 0/1, and dlqi ≤5, and when using locf or mnri to account for missing data (figures 2 and 3) • at week 56 in ecztend o easi-75 was achieved in 78% (130/167) of asian patients, 88% (66/75) of black patients and 83% (186/347) of white patients, as observed (figure 2) n 169 202 202 76 108 108 765 941 941 n 164 201 201 73 108 108 700 939 939 0 20 40 60 80 10 0 49 57 60 44 56 63 35 4042 r e s p o n d e rs , % worst weekly pruritus nrs ≤3 0 20 40 60 80 10 0 56 72 75 55 73 81 50 57 61 r e s p o n d e rs , % dlqi ≤5 asian mnri asian locf asian ao black ao black locf black mnri white ao white locf white mnri 0 20 40 60 80 10 0 7879 838283 88 7374 78 7879 838283 88 7374 78 r e s p o n d e rs , % easi-75 0 20 40 60 80 10 0 5859 646566 72 4647 51 r e s p o n d e rs , % easi-90 0 20 40 60 80 10 0 4950 53 6464 69 353537 r e s p o n d e rs , % iga 0/1 0 20 40 60 80 10 0 7677 818283 87 7071 74 r e s p o n d e rs , % easi ≤7 https://www.ismpp.org/gpp3 slide 1: efficacy and safety of up to two years of tralokinumab treatment in adults of different racial subgroups with moderate-to-severe atopic dermatitis skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 112 in-depth reviews review of the prevalence of cardiovascular and metabolic comorbidities of psoriasis jonathan vebman1, alexa choy1, christopher j. yao, mph1,2 1department of dermatology, icahn school of medicine at mount sinai, new york, ny 2unviersity of rochester school of medicine and dentistry, rochester, ny psoriasis is a common disease of the skin characterized by erythematous scaling plaques that can be linked to several other diseases that can have severe health consequences for the patient.1 there have been a number of research studies exploring the prevalence of comorbidities-such as myocardial/heart disease, stroke, diabetes, introduction introduction: psoriasis is a common disease that is linked with several other diseases. our goals were to analyze and present literature on prevalence of various psoriatic comorbidities, and provide an estimate of what percent of psoriasis patients might have or develop myocardial/cardiovascular/heart disease, stroke, diabetes, obesity, hypertension, or metabolic syndrome. methods: to collect the results, we searched pubmed to identify papers that studied the frequency of the most common comorbidities of psoriasis. we used about 20. the search terms used were the particular comorbidity (or synonyms) and psoriasis. papers were selected where the prevalence data were listed by percentages of the studied population. prevalence data from each paper were collected and charted, and then compared. we did not use data that concerned psoriatic arthritis. we also recorded outliers, where frequencies did not fit with the other data found. results: results for prevalence of myocardial/cardiovascular/heart disease were mixed, varying by age and severity of disease. there are few papers on prevalence of stroke, but our review suggests risk of stroke increases with severity of psoriasis. the prevalence of diabetes was largely between 10% and 20%. obesity’s prevalence was mostly between 15% and 30%, while hypertension hovered around 30%, and metabolic syndrome prevalence was mostly between 27% and 50%. conclusion: there are many comorbidities of psoriasis. the complex interaction between cutaneous inflammation and heart disease, stroke, diabetes, hypertension and metabolic syndrome raises many questions about cause and effect or simple association. abstract skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 113 obesity, hypertension, and metabolic syndrome-in various populations of psoriasis patients.1 this paper reviews the literature on the prevalence of specific psoriasis comorbidities and summarizes published findings on the frequency of each of these conditions in psoriasis patients. these results are discussed below and summarized in table 1. we aim to review the literature on the prevalence of specific psoriasis co-morbidities and summarizes published findings on the frequency of each of these conditions in psoriasis patients. these results are discussed below and summarized in table 1. the discussion below demonstrates that psoriasis can range from mild to severe and can be associated with a wide variety of comorbidities. as we better understand these variables, it becomes clear that the most effective treatment regimens are targeted to the specific disease manifestations, comorbidities, previous treatments, and impact on patients’ quality of life.2,3 we searched pubmed to identify papers that studied the frequency of the most common co-morbidities of psoriasis. the search terms used were the particular comorbidity (or synonyms) and psoriasis. papers were selected where the prevalence data were listed by percentages of the studied population. prevalence data from each paper were collected and charted, and then compared. we did not use data that concerned psoriatic arthritis. we also recorded outliers, where frequencies did not fit with the other data found, and they are discussed below. cardiovascular disease cardiovascular disease (or myocardial disease or heart disease) is one of the most commonly reported comorbidities of psoriasis. studies suggest mixed correlation with psoriasis. some studies showed, a relationship between increasing psoriasis severity and decreasing prevalence of cardiovascular disease, while others showed increasing risk with increasing severity of psoriasis. studies also showed that the increase in risk is particularly noteworthy in younger patients, partly because baseline risk of myocardial infarction is greater in older patients. it is also apparent that psoriasis with other cardiovascular risk factors increases the risk of heart disease. studies have reported very different prevalences of cardiovascular disease in psoriasis patients, ranging from 1.8% to 17.7%. according to a 2018 study published by hajiebrahimi et al, myocardial infarction had a prevalence of 2.5%, 2.3%, and 1.8%, when psoriasis was mild, moderate, and severe, respectively.4 it also suggested that younger patients were at higher risk of myocardial infarction. that range of results is supported by a 2015 study, which found that 2.59% of psoriasis patients had a major cardiovascular event as compared to 2.3% of controls.5 this study concluded that psoriasis was not-independent of other risk factors-associated with an increased risk of cardiovascular events.5 according to gelfand et al., the prevalence of myocardial infarction in mild and severe psoriasis was 1.8% (mild) and 2.9% (severe).6 it also indicated that the risk of myocardial infarction was increased in younger psoriasis patients as opposed to older patients. differing only slightly were the methods results skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 114 results of a ten-year review of malaysian psoriasis patients, which reported the prevalence of ischemic heart disease at 5.45% and the prevalence of cerebrovascular disease at 1.6%.7 a 2017 study of czech registry patients found the prevalence of coronary heart disease to be 4.9%.8 in contrast, schaarschmidt et al found that the prevalence of cardiovascular disease was 15%.9 even larger was the prevalence of cardiovascular disease reported by bmc health service research, at 17.7%.10 however, by far the highest prevalence was from assessment of possible drug interactions in patients with psoriasis and associated comorbid medical conditions: an observational study, which reported the prevalence of cardiovascular comorbidities at a staggering 77.3%.11 nevertheless, this paper noted that this unusually high percentage might be attributable to the fact that the study was focused in india, where cardiovascular comorbidities are more common. type 2 diabetes mellitus type 2 diabetes mellitus (dmii) is another common comorbidity of psoriasis. dmii‘s prevalence in psoriasis patients mostly hovers between 10% and 20%, higher than in control groups, with the prevalence increasing with the severity of psoriasis. according to a 2018 study on patients in swedish health registries, the prevalence of dmii is 7.6% (mild psoriasis), 8.0% (moderate-severe psoriasis), and 10.7% (severe psoriasis).4 french and czech studies found the prevalence of dmii in psoriatic patients to be 11%12 and 11.4%8 respectively. the czech study also refers to other european registries showing a prevalence of dmii in psoriasis patients of 9.9-12%. similarly, 2017 and 2018 studies found the prevalence of dmii in psoriasis patients to be 10%13 and 12%,14 respectively. another 2015 paper by schaarschmidt et al. reported the prevalence of dmii to be 14.5%9 while a review from the malaysian psoriasis registry, spanning 2007-2016, and a study of over 2,700 patients in the bringham psoriasis and psoriatic arthritis registries both found the prevalence of dmii in their cohorts to be at or near 17%.7,15 all other results were close to the results mentioned, and can be found in table 1 below, except for one unusual finding. far and away the largest percentage found of dmii in psoriasis patients was the 49.3% found in an observational study of psoriasis patients taking two or more drugs.11 stroke stroke is another serious comorbidity of psoriasis, but only a few studies assess the correlation between the two conditions. one study, however, demonstrated a 2.4% prevalence of stroke in individuals with mild psoriasis, 2.2% in individuals with moderate to severe psoriasis, and 1.1% in individuals with severe psoriasis.4 obesity obesity is a risk factor for cardiovascular and other diseases, and is also a common comorbidity of psoriasis, with reports of prevalence ranging from 15.2% (in a study of the czech national registry of psoriatic patients treated with biologics, and a comparison with other european registries)8 to 32.6% (a study of prevalence of metabolic disease and its various components comparing 95 psoriatic patients to 95 controls).16 a french study of 2,210 patients reports the prevalence to be 24%,12 while a large study over 48,000, and another of over 15,000 patients, report 20.36%5 and 24.3%7 respectively. trattner et al. report 27% in a study of plantar pustulosis.17 skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 115 hypertension hypertension can potentially cause many other diseases including cardiovascular disease and stroke. salunke et al. reports a prevalence rate of hypertension at 18.9%, but found that the rates increased with the duration of psoriasis.16 the malaysian study reports prevalence rate of 25.6%.7 many studies show results in a consistent range. hajiebrahimi et al. found the prevalence of hypertension in psoriasis patients at 29.9% (moderate psoriasis), 32.6% (moderate-severe psoriasis), and 36.5% (severe psoriasis).4 the french study mentioned above found the prevalence to be 26%.12 an australas journal of dermatology paper reports the rate of hypertension in psoriasis patients to be 30%,14 as does a brazilian study.18 the study of the czech registries reports the prevalence at 35.2%,8 and similarly, schaarschmidt et al. listed the prevalence of hypertension at 31.5%.9 similar to the czech study, a study of over 48,000 psoriasis patients and over 200,000 controls, spanning the years 1994-2009 showed a baseline of 15.39% prevalence of hypertension (compared to nearly 15% in the controls). by the end of the followup period (median of just over 5 years), the hypertension prevalence rose to 24.72% (mild psoriasis) and 31.62% (severe psoriasis), and 31.6% among controls.5 other studies found outcomes in similar prevalence ranges of 30%,18 32.8%,19 32%,17 34.3%,10 and 35%,13 respectively. in the brigham study the prevalence was reports at 45%.15 metabolic syndrome metabolic syndrome is a conglomerate of other diseases, defined generally to include several conditions that might include obesity, hypertension, and glucose intolerance.20 choudhary et al. surveyed 63 studies and found the occurrence of metabolic syndrome in psoriasis patients to be as high as 50% as compared to 15-25% among the general population.20 another study found the rate to be 30%.14 according to hajiebrahimi et al., metabolic syndrome has a prevalence of 50% in psoriasis patients.4 argote et al. also found a high 50% prevalence.13 a similarly high finding in a study of 97 patients, reports 49.4% prevalence.21 in the study by choudhary et al., a rigorous analysis of 63 papers, sorted by age, gender, and continent, studied 119,923 participants, of which 15,939 were psoriasis patients. metabolic syndrome was reported among 30.29% of psoriasis patients, compared with 21.70% in the control group.20 among these patients, 50% of south american patients were reported to have metabolic syndrome, compared to 27.14 in the control group, and 27.12 of asian patients, compared with 16.95% of the control patients.20 in a case-control study from western maharashtra, the reported prevalence rate was 38.9%.16 similarly, curco et al., in a 2018 paper, report a prevalence of 30%.14 the second-lowest score came from a plantar pustulosis study in which a cross-sectional analysis in 102 patients claimed a prevalence of 26%.17 however, the lowest prevalence rate, was a low 20.8%.22 there are many comorbidities of psoriasis. while the prevalence of each comorbidity varies according to publication as does the association with severity of psoriasis, it is clear that psoriasis is more than just a skin disease. the complex interaction between conclusion skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 116 cutaneous inflammation and heart disease, stroke, type 2 diabetes mellitus, hypertension and metabolic syndrome raises many questions about cause and effect or simple association. table 1. summary of prevalence of psoriasis’ comorbidities with pmid citations pmid myocardial/cardi ovascular/heart disease stroke diabetes mellitus obesity hypertension metabolic syndrome 29950900 hajiebrahimi 2.5% (mild ps), 2.3% (moderatesevere ps), 1.8% (severe ps) 2.4% (mild ps), 2.2% (moderatesevere ps), 1.1% (severe ps) 7.6% (mild ps), 8.0% (moderatesevere ps), 10.7% (severe ps) 29.9% (mild ps), 32.6% (moderatesevere ps), 36.5% (severe ps) 50.0% 26969480 phan 11% 24% 26% 28181669 kojanova 4.9% coronary heart disease 11.4% (9.9-12% various registries 15.2% 35.2% (21%-33.8% various registries) 26633680 schaarschmidt 15% 14.5% 31.5% 28969252 salunke 32.6% 18.9% 38.9% 25742120 parisi 2.59% cv event (v. 2.3% in controls) 5.64% (initial ps) ≥ 9.02% (severe) 20.36% 15.39% (initial ps) ≥ 24.72% (mild); 31.62% (severe) 29849578 mohd affandi ischemic heart disease 5.45; cerebrovascular disease 1.6% 17.2% 24.3% 25.6% 28814312 schneeweiss 17% 45% 28240341 curcó 12% 67% (obese or overweight) 30% 30% 28099594 duarte 30% 26402388 feldman 15.8% 32.8% 26829958 sherin 77.3% 49.3% 31595859 choudhary 27.12%50% 28482887 feldman 17.7% (17.45% moderate-severe, 17.8% mild ps) 14.2% (15.92% moderatesevere, 13.7% mild ps) 4.88% (5.18% moderatesevere, 4.79% mild ps) 34.3% (34.86% moderatesevere, 34.16% mild ps) skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 117 pmid myocardial/cardi ovascular/heart disease stroke diabetes mellitus obesity hypertension metabolic syndrome 28662815 argote 10% 35% 50% 30133617 ferdinando 49.4% 26316538 lai 20.8% 17032986 gelfand mi: 1.8% (mild ps) and 2.9% (severe) 28252813 trattner 27% 32% 26% conflict of interest disclosures: none funding: none corresponding author: jonathan iiai vebman department of dermatology, icahn school of medicine at mount sinai, new york, ny email: yivebman@gmail.com references: 1. mayo. psoriasis. https://www.mayoclinic.org/diseasesconditions/psoriasis/symptoms-causes/syc20355840?utm_source=google&utm_medium=a bstract&utm_content=psoriasis&utm_campaign= knowledge-panel. accessed. 2. kaushik sb, lebwohl mg. psoriasis: which therapy for which patient: focus on special populations and chronic infections. j am acad dermatol. 2019;80(1):43-53. 3. kaushik sb, lebwohl mg. psoriasis: which therapy for which patient: psoriasis comorbidities and preferred systemic agents. j am acad dermatol. 2019;80(1):27-40. 4. hajiebrahimi m, linder m, hagg d, et al. young patients with risk factors prevalent in the elderly differences in comorbidity depending on severity of psoriasis: a nationwide cross-sectional study in swedish health registers. clin epidemiol. 2018;10:705-715. 5. parisi r, rutter mk, lunt m, et al. psoriasis and the risk of major cardiovascular events: cohort study using the clinical practice research datalink. j invest dermatol. 2015;135(9):21892197. 6. gelfand jm, neimann al, shin db, wang x, margolis dj, troxel ab. risk of myocardial infarction in patients with psoriasis. jama. 2006;296(14):1735-1741. 7. mohd affandi a, khan i, ngah saaya n. epidemiology and clinical features of adult patients with psoriasis in malaysia: 10-year review from the malaysian psoriasis registry (2007-2016). dermatol res pract. 2018;2018:4371471. 8. kojanova m, fialova j, cetkovska p, et al. characteristics and risk profile of psoriasis patients included in the czech national registry biorep and a comparison with other registries. int j dermatol. 2017;56(4):428-434. 9. schaarschmidt ml, kromer c, herr r, et al. patient preferences for biologicals in psoriasis: top priority of safety for cardiovascular patients. plos one. 2015;10(12):e0144335. 10. feldman sr, tian h, gilloteau i, mollon p, shu m. economic burden of comorbidities in psoriasis patients in the united states: results from a retrospective u.s. database. bmc health serv res. 2017;17(1):337. 11. sherin r, udaykumar p. assessment of possible drug interactions in patients with psoriasis and associated comorbid medical conditions: an observational study. rev recent clin trials. 2016;11(2):128-134. 12. phan c, sigal ml, lhafa m, et al. metabolic comorbidities and hypertension in psoriasis patients in france. comparisons with french national databases. ann dermatol venereol. 2016;143(4):264-274. mailto:yivebman@gmail.com about:blank about:blank about:blank about:blank about:blank skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 118 13. argote a, mora-hernandez o, milena aponte l, et al. cardiovascular risk factors and carotid intima-media thickness in a colombian population with psoriasis. actas dermosifiliogr. 2017;108(8):738-745. 14. curco n, barriendos n, barahona mj, et al. factors influencing cardiometabolic risk profile in patients with psoriasis. australas j dermatol. 2018;59(2):e93-e98. 15. schneeweiss m, merola jf, karlson ew, solomon dh. rationale and design of the brigham cohort for psoriasis and psoriatic arthritis registry (coppar). bmc dermatol. 2017;17(1):11. 16. salunke as, nagargoje mv, belgaumkar va, tolat sn, chavan rb. association of metabolic syndrome in chronic plaque psoriasis patients and their correlation with disease severity, duration and age: a case control study from western maharashtra. j clin diagn res. 2017;11(8):wc06-wc10. 17. duarte gv, oliveira mf, follador i, silva ts, carvalho emf. diagnosis and underdiagnosis of comorbidities in psoriasis patients need for a multidisciplinary approach. an bras dermatol. 2016;91(6):743-747. 18. feldman sr, zhao y, shi l, tran mh. economic and comorbidity burden among patients with moderate-to-severe psoriasis. j manag care spec pharm. 2015;21(10):874-888. 19. choudhary s, pradhan d, pandey a, et al. the association of metabolic syndrome and psoriasis: a systematic review and meta-analysis of observational study. endocr metab immune disord drug targets. 2019. 20. ferdinando lb, fukumoto pk, sanches s, fabricio lhz, skare tl. metabolic syndrome and psoriasis: a study in 97 patients. rev assoc med bras (1992). 2018;64(4):368-373. 21. lai yc, yew yw. psoriasis as an independent risk factor for cardiovascular disease: an epidemiologic analysis using a national database. j cutan med surg. 2016;20(4):327333. copies of this e-poster obtained through qr, ar and/or text key codes are for personal use only and may not be reproduced without written permission of the authorspresented at the winter clinical dermatology conference hawaii®; january 13-18, 2023; kohala coast, hawaii https://scientificpubs.congressposter.com/p/fxn57o4wdbgx9yo1 disclosures this study was sponsored by pfizer inc. r. wolk, s.h. zwillich, h. tran, f. zhang, and l. takiya are employees of pfizer, inc and hold stock or stock options in pfizer, inc. m. piliang: consultant and/or investigator for pfizer, eli lilly, and proctor and gamble. c. lynde: speaker and/or consultant for abbvie, altius, amgen, aralez, arcutis, bausch health, bayer, boehringer ingelheim, bms, celgene, cipher, dermavant, eli lilly, fresnius kabi, gsk, innovaderm, intega skin, janssen, kyowa, la roche posay, leo pharma, l’oreal, medexus, merck, proctor and gamble, pediapharm, regeneron, roche, sanofi genzyme, sentrex, teva, tribute, ucb, valeant, and viatris; principal investigator for abbvie, amgen, aralez, arcutis, bausch health, bayer, boehringer ingelheim, bms, celgene, cipher, dermavant, eli lilly, gsk, innovaderm, janssen, kyowa, leo pharma, l’oreal, merck, pediapharm, regeneron, roche, sanofi genzyme, tribute, ucb, and valeant. b. king: honoraria and/or consultation fees from abbvie, aclaris therapeutics, altrubio, almirall, arena pharmaceuticals, bioniz therapeutics, bms, concert pharmaceuticals, dermavant sciences, eli lilly, incyte, leo pharma, otsuka/visterra, pfizer, regeneron, sanofi genzyme, twi biotechnology, and viela bio and speakers bureau fees from pfizer inc. p. mirmirani: investigator grants and/or research funding from concert pharmaceuticals, pfizer inc, and eli lilly. r. sinclair: professional services from abbvie, aerotech, amgen, arena, arcutis, aksebio, astrazeneca, ascend, bayer, boehringer ingelheim, bms, celgene, coherus biosciences, cutanea, connect, demira, eli lilly, galderma, gsk, janssen, leo pharma, medimmune, merck, msd, novartis, oncobiologics, pfizer, regeneron, reistone, roche, sanofi, samson clinical, sun pharma, and ucb. third-party medical writing assistance, provided by health interactions, inc, was funded by pfizer inc. references 1. islam n, et al. autoimmun rev. 2015;14:81-89. 2. king b, et al. poster presented at: 30th annual eadv meeting; september 29-october 2, 2021. 3. king b, et al. poster presented at: aad annual meeting; march 25-29, 2022. melissa piliang,1 charles lynde,2 brett king,3 paradi mirmirani,4 rodney sinclair,5 robert wolk,6 samuel h. zwillich,6 helen tran,7 fan zhang,6 liza takiya8 1department of dermatology, cleveland clinic, cleveland, oh, usa; 2department of medicine, university of toronto, toronto, on, canada; 3yale school of medicine, new haven, ct, usa; 4department of dermatology, the permanente medical group, vallejo, ca, usa; 5sinclair dermatology, melbourne, vic, australia; 6pfizer inc, groton, ct, usa; 7pfizer inc, new york, ny, usa; 8pfizer inc, collegeville, pa, usa sustained hair regrowth with ritlecitinib to week 48 in patients with alopecia areata: post hoc analysis of the allegro phase 2b/3 study conclusions • in this post hoc analysis, sustained scalp hair regrowth through week 48 was observed in the majority of patients with aa who had a salt score ≤20 or ≤10 response after week 24 of ritlecitinib treatment • the safety profile of ritlecitinib up to week 48 in salt ≤20 responders was consistent with that of the overall study population, which has been reported previously3 background • alopecia areata (aa) is an autoimmune disease that has an underlying immuno-inflammatory pathogenesis and is characterized by nonscarring hair loss ranging from small patches to complete scalp, face, and/or body hair loss1 • ritlecitinib, an oral jak3/tec family inhibitor, demonstrated efficacy and safety in patients aged ≥12 years with aa and ≥50% scalp hair loss in the allegro phase 2b/3 trial (nct03732807)2 significant improvements in the proportion of patients with severity of alopecia tool (salt) score ≤20 (≤20% of scalp without hair) at week 24 (primary endpoint) were observed in the 50 mg and 30 mg ritlecitinib treatment groups (+/200 mg loading dose) vs placebo (p<0.001) significant improvements in the proportions of patients with salt score ≤10 (≤10% of scalp without hair) with ritlecitinib vs placebo were also seen at week 24 (secondary endpoint) objective • to evaluate the maintenance of efficacy from week 24 to week 48 in patients with aa and ≥50% scalp hair loss treated with ritlecitinib methods study design • the allegro phase 2b/3 trial was an international, randomized, double-blind, placebo-controlled, combined doseranging and pivotal study (figure 1) • patients initially received daily ritlecitinib (± a 4-week 200-mg daily loading dose): 200/50, 200/30, 50, 30, or 10 mg (10 mg assessed for dose ranging only) or placebo for 24 weeks • during the 24-week extension period, ritlecitinib groups continued on 50-, 30-, or 10-mg maintenance doses, and patients initially assigned to placebo switched to 200/50 or 50 mg daily figure 1. allegro-2b/3 study design rit 200 mg qd rit 200 mg qd rit 50 mg qd rit 30 mg qd rit 10 mg qd placebo placebo rit 50 mg qd rit 30 mg qd rit 50 mg qd rit 30 mg qd rit 10 mg qd placebo placebo rit 50 mg qd rit 30 mg qd rit 50 mg qd rit 30 mg qd rit 10 mg qd rit 200/50 mg qd rit 50 mg qd placebo-controlled (24 weeks) study week extension (24 weeks) maintenance (20 weeks) loading (4 weeks) bl 2 4 8 12 18 26 28 34 40 4824 s cr ee ni ng r an do m iz at io n screening and randomization (35 days) n=132 n=66 n=65 n=63 n=130 n=132 n=130 bl, baseline; qd, once daily; rit, ritlecitinib. no other therapies were allowed during the study. study population • inclusion criteria included: age ≥12 years diagnosis of aa ≥50% scalp hair loss, including patients with at and au current aa episode duration of 6 months to 10 years • patients with other causes of alopecia or previous use of any jak inhibitor were excluded • this post hoc analysis included patients who received ritlecitinib 200/50, 200/30, 50, or 30 mg and had a salt ≤20 or ≤10 response at week 24 outcomes • the proportions of ritlecitinib-treated patients with clinical response at week 24, based on salt score ≤20 or salt score ≤10, who sustained this response through week 48, were assessed in this post-hoc analysis • definition of sustained response included: response at week 24 and week 48, based on salt score ≤20 or ≤10, and no loss of response (defined as salt score >20 or >10) at any time point between weeks 24 and 48 (weeks 28, 34, or 40) • patients with missing salt score data at weeks 28, 34, or 40 were included in the analysis if they had observed salt data at week 48; patients with missing data at week 48 were excluded from the analysis statistical analysis • descriptive analyses were used to evaluate the proportion of ritlecitinib-treated patients with salt score ≤20 or salt score ≤10 response at week 24, who sustained this response through week 48 • 95% cis were calculated based on normal approximation results table 1. baseline characteristics of patients with salt score ≤20 response at week 24 ritlecitinib qd 200/50 mg (n=38) 200/30 mg (n=27) 50 mg (n=29) 30 mg (n=17) age mean (sd), years 33.7 (14.2) 31.8 (12.2) 34.0 (14.5) 36.9 (14.7) 12-17 years, n (%) 5 (13.2) 3 (11.1) 4 (13.8) 3 (17.6) ≥18 years, n (%) 33 (86.8) 24 (88.9) 25 (86.2) 14 (82.4) female, n (%) 28 (73.7) 21 (77.8) 25 (86.2) 11 (64.7) white, n (%) 25 (65.8) 16 (59.3) 18 (62.1) 12 (70.6) patients with at/au*, n (%) 8 (21.1) 7 (25.9) 4 (13.8) 4 (23.5) baseline salt score, mean (sd)† 84.4 (16.0) 80.9 (18.2) 78.9 (16.9) 77.6 (19.2) duration of disease since aa diagnosis, mean (sd), years 9.9 (8.5) 9.2 (8.0) 7.1 (8.9) 6.9 (5.9) duration of current aa episode, mean (sd), years 2.5 (2.2) 3.1 (2.4) 2.4 (2.5) 2.1 (2.6) aa, alopecia areata; at, alopecia totalis; au, alopecia universalis; qd, once daily; salt, severity of alopecia tool. *patients in the at/au category had a salt score of 100 at baseline (regardless of the category in the aa history case report form). †mean (sd) baseline salt score for all patients including patients with at/au. • in the 200/50, 200/30, 50, 30 mg ritlecitinib treatment groups, 36/132, 27/130, 28/130, and 16/132 patients, respectively, had a salt score ≤20 response at week 24 and had salt data at week 48 of these, 85% to 100% had a sustained response through week 48 (figure 2) figure 2. sustained salt score ≤20 responses 0 20 40 60 80 100 ritlecitinib 200/50 mg ritlecitinib 200/30 mg ritlecitinib 50 mg ritlecitinib 30 mg 91.7% 85.2% 89.3% 100% p at ie nt s w ith s us ta in ed s a lt ≤ 20 r es po ns e fr om w ee k 24 th ro ug h w ee k 48 , % (9 5% c i) salt, severity of alopecia tool. • similarly, 26/132, 16/130, 16/130, and 12/132 patients in the 200/50, 200/30, 50, 30 mg groups, respectively, had a salt score ≤10 response at week 24 and had salt data at week 48 of these, 69% to 92% had a sustained response through week 48 (figure 3) figure 3. sustained salt score ≤10 responses 0 20 40 60 80 100 ritlecitinib 200/50 mg ritlecitinib 200/30 mg ritlecitinib 50 mg ritlecitinib 30 mg p at ie nt s w ith s us ta in ed s a lt ≤ 10 r es po ns e fr om w ee k 24 th ro ug h w ee k 48 , % (9 5% c i) 84.6% 68.8% 87.5% 91.7% salt, severity of alopecia tool. safety • ritlecitinib was well tolerated up to week 48 in patients with salt score ≤20 response at week 24; most adverse events (aes) were mild or moderate in severity, 2 serious aes were reported, and 2 patients permanently discontinued due to aes (table 2) table 2. safety summary up to week 48 in patients with salt score ≤20 response at week 24 ritlecitinib qd 200/50 mg (n=38) 200/30 mg (n=27) 50 mg (n=29) 30 mg (n=17) patients with aes 35 (92.1) 20 (74.1) 27 (93.1) 14 (82.4) patients with saes* 0 1 (3.7) 1 (3.4) 0 patients permanently discontinued due to aes† 0 1 (3.7) 1 (3.4) 0 most frequent aes‡ upper respiratory tract infection 11 (28.9) 2 (7.4) 3 (10.3) 0 headache 7 (18.4) 1 (3.7) 8 (27.6) 4 (23.5) nasopharyngitis 7 (18.4) 4 (14.8) 2 (6.9) 3 (17.6) ae, adverse event; qd, once daily; sae, serious adverse event; salt, severity of alopecia tool. *saes were chemical poisoning and suicidal behavior in 1 patient in the 200/30 mg group and pulmonary embolism in 1 patient in the 50 mg group. †patients who had an ae record indicating that the patient was permanently discontinued from the study or study drug. ‡aes occurring in ≥5% of patients in any treatment group by preferred term (all causalities). secukinumab in moderate to severe hidradenitis suppurativa: primary endpoint analysis from the sunshine and sunrise phase 3 trials alexa b. kimball,1 afsaneh alavi,2 gregor b.e. jemec,3 alice gottlieb,4 xiaoling wei,5 magdalena b. wozniak,6 lorenz uhlmann,7 angela llobet martinez,7 deborah keefe,8 ruvie martin,8 li chen,8 elisa muscianisi8 1harvard medical school and clinical laboratory for epidemiology and applied research in skin (clears), department of dermatology, beth israel deaconess medical center, boston, ma, usa; 2department of dermatology, mayo clinic, rochester, mn, usa; 3department of dermatology, zeeland university hospital, health sciences faculty, university of copenhagen, roskilde, denmark; 4department of dermatology, icahn school of medicine at mount sinai, new york, ny, usa; 5novartis pharma shanghai, china; 6novartis ireland limited, dublin, ireland; 7novartis pharma ag, basel, switzerland; 8novartis pharmaceuticals corporation, east hanover, nj, usa synopsis • hidradenitis suppurativa (hs) is a chronic autoinflammatory keratinization disease of the skin involving the hair follicle characterized by nodules, abscesses and draining tunnels1 • hs is characterized by high patient burden and a recognized need for novel therapeutic options2 • the il-17 pathway has been implicated as a key orchestrator of inflammation in hs3 • the sunshine and sunrise studies investigated the efficacy and safety of secukinumab, an anti-il-17a agent, in the treatment of moderate to severe hs objective • to describe the primary endpoint analysis (week 16) results from sunshine (nct03713619) and sunrise (nct03713632), two double-blind, identical, phase 3 randomised controlled trials of secukinumab in patients with moderate to severe hs methods study design • sunshine and sunrise were two randomised, double-blind, multicentre studies assessing short (16 weeks) and long-term (up to 1 year) efficacy, safety, and tolerability of two subcutaneous (s.c.) sec dose regimens in adult patients with moderate to severe hs • a total of 1084 patients (mean age 36.2, 56.3% female) across 219 sites worldwide were randomized in sunshine (n=541) and sunrise (n=543) • in each study, adult patients with moderate to severe hs were randomly assigned in a 1:1:1 fashion to receive s.c. secukinumab 300 mg every 2 (secq2w) or 4 weeks (secq4w), or placebo (figure 1) figure 1. sunshine and sunrise study design 1: 1: 1 al lo ca tio n 30 0m g q 2w :3 00 m g q 4w :p la ce bo primary endpoint analysis screening treatment period 1 week -4 bsl week 4 8 12 16 secq4w secq2w pbo treatment allocation sec s.c pbo s.c sec induction phase treatment period 2 20 24 28 32 36 40 44 48 52 60 f8 eot2eot1 secq4w secq2w secq4w secq2w 1:1 follow-up eligible patients will enter extension study (nct04179175) bsl, baseline; eot1/eot2: end of treatment period 1/2; f8, end of 8-week follow-up period; pbo, placebo; pro, patient-reported outcome; q2w, every two weeks; q4w, every four weeks; s.c., subcutaneous; sec, secukinumab 300 mg. endpoints/assessments • primary endpoint (week 16): to demonstrate superiority of secukinumab versus placebo based on hiscr (defined as at least a 50% decrease in an count with no increase in the number of abscesses and/or in the number of draining fistulae relative to baseline). • secondary endpoints (week 16): percentage change in an count from baseline, flares, and achievement of nrs30 among patients with a baseline skin pain nrs ≥3 (defined as at least a 30% reduction and at least a 2-unit reduction in baseline patient’s global assessment of skin pain at worst) • exploratory objectives: to evaluate long-term safety, efficacy, and tolerability of secukinumab and its effect on patient reported outcomes (pros) and biomarkers results patient demographics and baseline characteristics • n=541 (sunshine) and n=543 (sunrise) randomized; 509 (94.1%) and 506 (93.2%) patients completed treatment period 1 (week 16), respectively • discontinuation rate of treatment up to week 16 was very low and balanced despite covid-19 pandemic (table 1) table 1. sunshine and sunrise: patient disposition disposition/ reason, n (%) sunshine sunrise secq2w n=181 secq4w n=180 placebo n=180 total n=541 secq2w n=180 secq4w n=180 placebo n=183 total n=543 completed week 16 168 (92.8) 169 (93.9) 172 (95.6) 509 (94.1) 170 (94.4) 169 (93.9) 167 (91.3) 506 (93.2) discontinued treatment 13 (7.2) 11 (6.1) 8 (4.4) 32 (5.9) 10 (5.6) 11 (6.1) 16 (8.7) 37 (6.8) primary reason for discontinuing treatment up to week 16 patient decision 4 (2.2) 9 (5.0) 5 (2.8) 18 (3.3) 6 (3.3) 6 (3.3) 8 (4.4) 20 (3.7) adverse event 4 (2.2) 0 (0.0) 1 (0.6) 5 (0.9) 1 (0.6) 4 (2.2) 4 (2.2) 9 (1.7) other* 5 (2.8) 2 (1.2) 2 (1.2) 9 (1.7) 3 (1.7) 1 (0.6) 4 (2.2) 8 (1.5) *other includes the following reasons: lost to follow-up, physician decision, technical problems, lack of efficacy and pregnancy. covid-19, coronavirus disease 2019; n, number of patients in group; n, number of patients with characteristic; q2w, every two weeks; q4w, every four weeks; sec, secukinumab 300 mg. • 59% of participants were categorized as hurley stage ii and 37% as hurley stage iii (table 2) • about one quarter of participants had received previous systemic biologic therapy (mostly anti-tnfs) efficacy: primary endpoints • the primary endpoint was met in both the sunshine and sunrise studies • greater response rates for secukinumab compared to placebo were seen at all time-points from week 2 to week 16, with a rapid onset of action by week 2 (figure 2) table 2. sunshine and sunrise results: baseline characteristics characteristic sunshine sunrise secq2w n=181 secq4w n=180 placebo n=180 total n=541 secq2w n=180 secq4w n=180 placebo n=183 total n=543 age group in years, n (%) <30 58 (32.0) 69 (38.3) 51 (28.3) 178 (32.9) 52 (28.9) 60 (33.3) 57 (31.1) 169 (31.1) 30‒<40 56 (30.9) 45 (25.0) 70 (38.9) 171 (31.6) 48 (26.7) 61 (33.9) 65 (35.5) 174 (32.0) 40‒<65 64 (35.4) 63 (35.0) 58 (32.2) 185 (34.2) 77 (42.8) 57 (31.7) 59 (32.2) 193 (35.5) ≥65 3 (1.7) 3 (1.7) 1 (0.6) 7 (1.3) 3 (1.7) 2 (1.1) 2 (1.1) 7 (1.3) sex, n (%) female 102 (56.4) 100 (55.6) 102 (56.7) 304 (56.2) 98 (54.4) 103 (57.2) 105 (57.4) 306 (56.4) weight groups (kg), n (%) ≥90 99 (54.7) 100 (55.6) 97 (53.9) 296 (54.7) 94 (52.2) 91 (50.6) 91 (49.7) 276 (50.8) time since diagnosis of hs, mean±sd years 7.4±7.98 6.6±6.73 7.5±7.00 7.1±7.25 7.1±7.04 8.2±8.42 7.0±6.65 7.4±7.41 baseline hurley stage, n (%) ii 104 (57.5) 107 (59.4) 121 (67.2) 332 (61.4) 92 (51.1) 106 (58.9) 110 (60.1) 308 (56.7) iii 70 (38.7) 63 (35.0) 51 (28.3) 184 (34.0) 82 (45.6) 68 (37.8) 70 (38.3) 220 (40.5) previous exposure to systemic biologic therapy, n (%) yes 44 (24.3) 39 (21.7) 46 (25.6) 129 (23.8) 36 (20.0) 42 (23.3) 48 (26.2) 126 (23.2) current systemic antibiotic use (i.e., antibiotic strata), n (%) yes 26 (14.4) 25 (13.9) 18 (10.0) 69 (12.8) 18 (10.0) 21 (11.7) 19 (10.4) 58 (10.7) hs, hidradenitis suppurativa; n, number of patients in group; n, number of patients with characteristic; q2w, every two weeks; q4w, every four weeks; sd, standard deviation; sec, secukinumab 300 mg. figure 2. primary efficacy endpoint: hiscr up to week 16 sunshine sunrise secq2w wk 16 secq4w wk 16 placebo wk 16 45.0% (p=0.0070) 41.8% (p=0.0418) 33.7% secq2w wk 16 secq4w wk 16 placebo wk 16 42.3% (p=0.0149) 46.1% (p=0.0022) 31.2% 45.0 41.8 33.7 0 10 20 30 40 50 60 0 2 4 6 8 10 12 14 16 h is c r r es po nd er s (% ) week secq2w (n=181) secq4w (n=180) placebo (n=180) secq2w (n=180) secq4w (n=180) placebo (n=183) 42.3 46.1 31.2 0 10 20 30 40 50 60 0 2 4 6 8 10 12 14 16 h is c r r es po nd er s (% ) week end of induction phase end of induction phase one-sided nominal p-values are based on a logistic regression model, the primary estimand, and multiple imputation. error bars represent 95% ci. green represents statistical significance and red represents non-significance compared with placebo. ci, confidence intervals; hiscr, hidradenitis suppurativa clinical response; n, number of patients in group; q2w, every two weeks; q4w, every four weeks; sec, secukinumab 300 mg; wk, week. efficacy: secondary endpoints • in both studies, secukinumab reduced the abscess and inflammatory nodule count in patients with moderate to severe hs (figure 3) – a decrease in an count with secukinumab appeared as early as week 2, and further improved up to week 16 in both studies figure 3. percent change from baseline in an count end of induction phase end of induction phase -46.8 -42.4 -24.3 ˗60 ˗50 ˗40 ˗30 ˗20 ˗10 0 0 2 4 6 8 10 12 14 16 c ha ng e fr om b as el in e (% ) i n a n c ou nt sunshine secq2w wk 16 secq4w wk 16 placebo wk 16 -46.8% (p<0.0001) -42.4% (p=0.0004) -24.3% week secq2w (n=181) secq4w (n=180) placebo (n=180) -39.3 -45.5 -22.4 ˗60 ˗50 ˗40 ˗30 ˗20 ˗10 0 0 2 4 6 8 10 12 14 16 c ha ng e fr om b as el in e (% ) i n a n c ou nt sunrise secq2w wk 16 secq4w wk 16 placebo wk 16 -39.3% (p=0.0051) -45.5 % (p=0.0001) -22.4% secq2w (n=180) secq4w (n=180) placebo (n=183) week one-sided nominal p-values are based on an ancova, the secondary estimand, and multiple imputation. error bars represent se. green represents statistical significance and red represents non-significance compared with placebo. an, abscess and inflammatory nodule; ancova, analysis of covariance; hs, hidradenitis suppurativa; n, number of patients in group; q2w, every two weeks; q4w, every four weeks; se, standard error; sec, secukinumab 300 mg; wk, week. • the proportion of patients experiencing flares was lower with secukinumab compared to placebo at all timepoints from week 2 to week 16, with a rapid onset of action starting at week 2 in both studies (figure 4) figure 4. proportion of patients experiencing flares (%)* end of induction phase end of induction phase 15.4 23.2 29.0 0 10 20 30 40 0 0 10 20 30 40 2 4 6 8 10 12 14 16 20 4 6 8 10 12 14 16 p ro po rt io n of p at ie nt s ex pe ri en ci ng fl ar es (% ) p ro po rt io n of p at ie nt s ex pe ri en ci ng fl ar es (% ) 20.1 15.6 27.0 sunshine secq2w wk 16 secq4w wk 16 placebo wk 16 15.4% (p=0.0010) 23.2% (p=0.0926) 29.0% secq2w (n=181) secq4w (n=180) placebo (n=180) sunrise secq2w wk 16 secq4w wk 16 placebo wk 16 20.1% (p=0.0732) 15.6% (p=0.0049) 27.0% secq2w (n=180) secq4w (n=180) placebo (n=183) *flares are defined as as at least a 25% increase in an count with a minimum increase of 2 an relative to baseline. one-sided nominal p-values are based on a logistic regression model, the secondary estimand, and multiple imputation. error bars represent 95% ci. green represents statistical significance and red represents non-significance compared with placebo. an, abscess and inflammatory nodule; ci, confidence intervals; hs, hidradenitis suppurativa; n, number of patients in group; q2w, every two weeks; q4w, every four weeks; sec, secukinumab 300 mg; wk, week. scan to download a copy of this poster to download a copy of this poster, visit the web at: http://novartis.medicalcongressposters.com/default.aspx?doc=2cf04 copies of this poster obtained through quick response (qr) code are for personal use only and may not be reproduced without written permission of the authors • secukinumab reduced skin pain in patients with moderate to severe hs (figure 5) – nrs30 was defined as ≥30% reduction and a ≥2-unit reduction from baseline in patient’s global assessment of skin pain. only patients with a baseline nrs≥3 were included in the analysis of skin pain – pooled crp levels demonstrate numerical reductions from placebo group • a larger treatment effect was achieved with secukinumab compared with the placebo regimen as early as week 4 and sustained up to week 16 figure 5. patients’ reduction in pain end of induction phase end of induction phase38.9 35.8 26.9 0 10 20 30 40 50 60 0 2 4 6 8 10 12 14 16p at ie nt s ac hi ev in g n r s 30 (% ) week 12.8 11.5 14.7 0 5 10 15 20 25 0 2 4 6 8 10 12 14 16 c r p (m g/ l) week sunshine and sunrise nrs30 (pooled) sunshine and sunrise crp (pooled) secq2w wk 16 secq4w wk 16 placebo wk 16 38.9% (p=0.0031) 35.8% (p=0.0249) 26.9% secq2w (n=233) secq4w (n=222) placebo (n=230) secq2w (n=361) secq4w (n=360) placebo (n=363) one-sided nominal p-values are based on a logistic regression model, the secondary estimand, and multiple imputation. error bars represent 95% ci (nrs30) or se (crp). green represents statistical significance and red represents non-significance compared with placebo. ci, confidence intervals; crp, c-reactive protein; hs, hidradenitis suppurativa; n, number of patients in group; nrs, numerical rating score; q2w, every two weeks; q4w, every four weeks; se, standard error; sec, secukinumab 300 mg; wk, week. safety • secukinumab was well tolerated, consistent with the known safety profile in other approved indications (table 3) table 3. summary of secukinumab safety through week 16 outcome, n (%) sunshine sunrise secq2w n=181 secq4w n=180 placebo n=180 secq2w n=180 secq4w n=180 placebo n=183 safety overview any aes 122 (67.4) 118 (65.6) 120 (66.7) 113 (62.8) 114 (63.3) 116 (63.4) all non-fatal saes 3 (1.7) 3 (1.7) 6 (3.3) 6 (3.3) 6 (3.3) 5 (2.7) deaths 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) discontinued study treatment due to aes 5 (2.8) 1 (0.6) 1 (0.6) 1 (0.6) 4 (2.2) 4 (2.2) aes of special interest infections and infestations (soc) 59 (32.6) 51 (28.3) 53 (29.4) 52 (28.9) 59 (32.8) 62 (33.9) urti (hlt) 33 (18.2) 26 (14.4) 22 (12.2) 27 (15.0) 21 (11.7) 29 (15.8) fungal infectious disorders (hlgt) 12 (6.6) 1 (0.6) 7 (3.9) 7 (3.9) 13 (7.2) 3 (1.6) candida infections (hlt) 2 (1.1) 1 (0.6) 4 (2.2) 5 (2.8) 5 (2.8) 2 (1.1) hypersensitivity (smq, narrow) 12 (6.6) 9 (5.0) 9 (5.0) 7 (3.9) 5 (2.8) 7 (3.8) malignant or unspecified tumours* (smq) 0 (0.0) 0 (0.0) 1 (0.6) 0 (0.0) 1 (0.6) 1 (0.5) mace 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) ibd† 0 (0.0) 0 (0.0) 0 (0.0) 1 (0.6) 1 (0.6) 0 (0.0) *excludes non-melanoma skin cancers; †one case of ibd and one case of ulcerative colitis was reported. ae, adverse event; aesi, adverse event of special interest; hlgt, high-level group terms; hlt, high-level term; ibd, inflammatory bowel disease; mace, major adverse cardiovascular events; meddra, medical dictionary for regulatory activities; n, number of patients with outcome; n, number of patients in group; q2w, every two weeks; q4w, every four weeks; sae, serious adverse event; sec, secukinumab; smq, standardised meddra queries; soc, system organ class; urti, upper respiratory tract infection. conclusions • the sunshine and sunrise phase 3 trials both met their primary endpoint (hiscr) demonstrating superiority of secukinumab over placebo with rapid symptom relief in patients with moderate to severe hs • secukinumab achieved the majority of its secondary endpoints of an count, flares and pain while demonstrating positive numeric trends in safety and efficacy in dlqi and crp • secukinumab was well tolerated in patients with moderate to severe hs, consistent with the known favorable safety profile in other approved indications references 1. frew j. jaad int. 2020;1(1):62-72. 2. ingram jr, et al. eur acad dermatol venereol. 2022;36(9):1597-1605. 3. zouboulis cc, et al. exp dermatol. 2021;30(suppl 1):8-17. financial disclosures abk is a consultant and investigator for abbvie, bristol meyers squibb, janssen, eli lilly, novartis, pfizer, and ucb; investigator for incyte and anaptysbio; consultant for bayer, boehringer ingelheim, ventyx, moonlake, lilly, concert, evoimmune, sonoma bio, sanofi, receives fellowship funding from janssen; and serves on the board of directors for almirall. aa has received honoraria as a consultant or advisory board participant from abbvie, janssen, novartis, boehringer-ingelheim, inflarx, and ucb and is an investigator for processa and boehringer-ingelheim. gbej has served as a consultant for abbvie, coloplast, leo pharma, novartis, ucb, and inflarx; as an investigator for abbvie, leo pharma, novartis, regeneron, ucb, and inflarx; has received unrestricted grants from abbvie, leo pharma, and novartis; has served on adboards for abbvie, janssen-pharma, msd, and novartis; and as a speaker for abbvie, coloplast, leo pharma, and galderma. ag has received honoraria as an advisory board member, non-promotional speaker or consultant for: amgen, anaptysbio, avotres therapeutics, boehringer ingelheim, bristol-myers squibb, dermavant, eli lilly, janssen, novartis, pfizer, sanofi, sun pharmaceutical industries, ucb, and xbiotech (stock options for an ra project). ag has also received research/educational grants from: anaptysbio, janssen, novartis, ortho dermatologics, sun pharmaceutical industries, bristol-myers squibb and ucb; all funds go to icahn school of medicine at mount sinai. xw is an employee at novartis pharma shanghai, china. mbw is an employee and stockholder at novartis ireland limited, dublin. lu, and alm are employees and stockholders at novartis pharma ag, basel, switzerland. dk, rm, lc, and em are employees and stockholders at novartis pharmaceuticals corporation, east hanover, nj, usa. acknowledgements all authors participated in the development of poster for the presentation. the authors thank swati shrivastava and nivedita jangale of novartis healthcare pvt ltd, hyderabad for editorial and medical writing support, which was funded by novartis pharma ag, basel, switzerland in accordance with the good publication practice (gpp3) guidelines (http://www.ismpp.org/gpp3) this investigation was sponsored by novartis pharma ag, basel, switzerland. originally presented as an oral presentation at the 31st eadv congress, september 7−10, 2022; milan italy. poster presented at: winter clinical dermatology conference, january 13 18, 2023, hawaii deucravacitinib long-term efficacy with continuous treatment in plaque psoriasis: 2-year results from the phase 3 poetyk pso program mark lebwohl,1 richard b warren,2 howard sofen,3 shinichi imafuku,4 carle paul,5 jacek c szepietowski,6 lynda spelman,7 thierry passeron,8 elizabeth colston,9 lauren hippeli,9 andrew napoli,9 renata m kisa,9 subhashis banerjee,9 alan menter,10 diamant thaçi,11 andrew blauvelt12 1icahn school of medicine at mount sinai, new york, ny, usa; 2dermatology centre, salford royal nhs foundation trust, nihr manchester biomedical research centre, the university of manchester, manchester, uk; 3ucla school of medicine, los angeles, ca, usa; 4fukuoka university hospital, fukuoka, japan; 5toulouse university and chu, toulouse, france; 6wrocław medical university, wrocław, poland; 7veracity clinical research, brisbane, qld, australia; 8côte d’azur university, university hospital of nice, nice, france; 9bristol myers squibb, princeton, nj, usa; 10baylor university medical center, dallas, tx, usa; 11university of lübeck, lübeck, germany; 12oregon medical research center, portland, or, usa presented at the winter clinical dermatology conference hawaii®; january 13-18, 2023; kohala coast, hi this is an encore of the 2022 31st eadv congress presentation email: lebwohl@aol.com copies of this poster are for personal use only and may not be reproduced without written permission from the authors. synopsis • tyrosine kinase 2 (tyk2) is an intracellular enzyme that mediates signaling of cytokines (eg, interleukin-23, type i interferons) involved in psoriasis pathogenesis1 • deucravacitinib, an oral, selective, allosteric tyk2 inhibitor, is approved by the us food and drug administration for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy2 • deucravacitinib binds to the tyk2 regulatory domain rather than to the more conserved catalytic domain where janus kinase (jak) 1/2/3 inhibitors bind1 (figure 1) figure 1. mechanism of action of deucravacitinib tyk2 deucravacitinib (allosteric inhibitor class) unique tyk2 regulatory domain catalytic domain (highly conserved across jak family) atp-binding active site (approved jak inhibitor class) •  ≥100-fold greater selectivity for tyk2 vs jak 1/3 • ≥2000-fold greater selectivity for tyk2 vs jak 2 selectivity in cells1,3: atp, adenosine 5′-triphosphate; jak, janus kinase; tyk2, tyrosine kinase 2. • deucravacitinib was studied at 6 mg once daily in two global phase 3 pivotal trials, poetyk pso-1 (nct03624127) and pso-2 (nct03611751)4,5 — only poetyk pso-1 included a continuous deucravacitinib treatment arm from day 1 to week 52 — placebo patients crossed over to deucravacitinib at week 16 in both trials • poetyk pso-1 demonstrated (figure 26): — significantly greater response rates for ≥75% reduction from baseline in psoriasis area and severity index (pasi 75) and static physician’s global assessment score of 0 (clear) or 1 (almost clear) with a ≥2-point improvement from baseline (spga 0/1) at week 16 with deucravacitinib vs placebo and apremilast4 — clinical efficacy that was maintained through week 52 with continuous deucravacitinib treatment7 • patients completing the poetyk pso-1 trial could enroll in the poetyk long-term extension (lte) trial and receive open-label deucravacitinib 6 mg once daily • the 2-year safety profile of deucravacitinib in the poetyk lte trial was consistent with that observed from weeks 0–52 of the poetyk pso-1 and pso-2 trials, and there were no emerging safety signals8 figure 2. clinical efficacy in poetyk pso-1 (nri)6 deucravacitinib (n = 332) placebo crossoversa (n = 145)placebo (n = 166) spga 0/1 58.4% 69.3% 65.1% 12.7% 44.1% 68.3% 0 25 50 75 100 pasi 75 53.6% 58.7% 52.7% 7.2% 39.3% 53.8% 0 25 50 75 100 week 16 week 24 week 52 n = 194 21 64230 99216 week 16 week 24 week 52 n = 178 12 57195 78175 % o f p at ie n ts % o f p at ie n ts apatients initially randomized to placebo crossed over to deucravacitinib at week 16. nri, nonresponder imputation; pasi 75, ≥75% reduction from baseline in psoriasis area and severity index; spga 0/1, static physician’s global assessment score of 0 (clear) or 1 (almost clear) with a ≥2-point improvement from baseline. objectives • to examine long-term efficacy responses in poetyk pso-1 patients who: — received continuous deucravacitinib treatment from day 1 and entered the poetyk lte — achieved pasi 75 response on deucravacitinib at week 16, continued on deucravacitinib, and entered the poetyk lte methods study designs and analysis populations • the study designs for the poetyk pso-1 and lte trials are illustrated in figure 3 • patients meeting the following criteria were eligible to enroll in the study: — age ≥18 years — diagnosis of moderate to severe plaque psoriasis • baseline pasi ≥12, spga ≥3, and body surface area involvement ≥10% • patient randomization in poetyk pso-1 was stratified by geographic region, body weight, and prior biologic use • analysis populations were defined as: — continuous deucravacitinib treatment from baseline: patients who received continuous deucravacitinib from day 1 (week 0) and entered the poetyk lte • since results with nonresponder imputation (nri) were shown earlier from weeks 0–52,4,5 only weeks 52–112 results are shown here — continuous deucravacitinib week 16 pasi 75 responders: patients who received continuous deucravacitinib from day 1, achieved pasi 75 at week 16, and entered the poetyk lte figure 3. poetyk pso-1 and lte study designs 100 poetyk pso-1 deucravacitinib 6 mg qd placebo (n = 166) deucravacitinib 6 mg qd apremilast 30 mg bid titrate* p o e t y k p so -1 1 :2 :1 r an d o m iz at io n deucravacitinib 6 mg qd (n = 332) apremilast 30 mg bida (n = 168) cumulative exposure (weeks) 16 24 520 primary endpoint b li n d e d s w it c h t o o p e n -l a b e l d e u c r a v a c it in ib open-label deucravacitinib 6 mg qdb poetyk lte 14856 60 68 76 88 112 124 1364 8 12 20 28 32 36 40 44 48 480 964 8 16 24 36 60 72 84exposure relative to lte (weeks) <pasi 50 ≥pasi 50 from armstrong aw, et al. deucravacitinib versus placebo and apremilast in moderate to severe plaque psoriasis: efficacy and safety results from the 52-week, randomized, double-blinded, placebo-controlled phase 3 poetyk pso-1 trial. j am acad dermatol. 2023;88:29-39. this work is licensed under a creative commons attribution license (cc by-nc-nd 4.0). https://creativecommons.org/licenses/by-nc-nd/4.0/. aapremilast was titrated from 10 mg qd to 30 mg bid over the first 5 days of dosing. bdata reported through the 120-day lte cutoff date of october 1, 2021. bid, twice daily; lte, long-term extension; pasi, psoriasis area and severity index; pasi 50, ≥50% reduction from baseline in pasi; qd, once daily. outcome measures • efficacy was assessed in patients with up to 112 weeks (≈2 years) of continuous deucravacitinib exposure as of the cutoff date of october 1, 2021 — pasi 75 — ≥90% reduction from baseline in pasi (pasi 90) — spga 0/1 • in addition to the as-observed analysis, 2 methods of imputation for missing data were used to evaluate long-term efficacy: — treatment failure rules (tfr)9: patients who discontinued treatment or the study due to worsening of psoriasis or lack of efficacy were imputed as nonresponders — modified nri (mnri)10: multiple imputation analysis was used for imputation of missing values, and patients who discontinued due to worsening of psoriasis were imputed as nonresponders • only patients who discontinued or had reached week 112 by the cutoff date of october 1, 2021, were included results baseline patient demographics and disease characteristics • baseline demographics and disease characteristics for poetyk pso-1 patients randomized to deucravacitinib who rolled over to the poetyk lte are presented in table 1 • a total of 332 patients were randomized to deucravacitinib — 265 patients completed the study and entered the poetyk lte — 173 pasi 75 responders at week 16 entered the poetyk lte table 1. baseline patient demographics and disease characteristics parameter patients randomized to deucravacitinib entering poetyk lte total (n = 265) week 16 pasi 75 responders (n = 173) age, mean (sd), y 46.0 (13.7) 45.2 (14.0) weight, mean (sd), kg 87.0 (22.2) 84.7 (22.4) female, n (%) 87 (32.8) 58 (33.5) race, n (%) white 211 (79.6) 133 (76.9) asian 51 (19.2) 37 (21.4) black or african american 1 (0.4) 1 (0.6) other 2 (0.8) 2 (1.2) age at disease onset, mean (sd), y 29.8 (15.1) 29.8 (15.1) disease duration, mean (sd), y 17.0 (12.2) 16.2 (11.8) pasi, mean (sd) 21.8 (8.3) 22.6 (8.9) spga, n (%) 3 (moderate) 208 (78.5) 129 (74.6) 4 (severe) 57 (21.5) 44 (25.4) bsa involvement, mean (sd), % 27.2 (15.6) 28.3 (15.6) bsa, body surface area; lte, long-term extension; pasi, psoriasis area and severity index; pasi 75, ≥75% reduction from baseline in pasi; sd, standard deviation; spga, static physician’s global assessment. pasi 75 and pasi 90 outcomes • overall, pasi 75 responses were consistent from weeks 52–112 in all patients with continuous deucravacitinib treatment (figure 4) • pasi 75 response rates were maintained from weeks 16–112 in week 16 pasi 75 responders (figure 5) • overall, pasi 90 responses were consistent from weeks 52–112 (figure 6) • pasi 90 response rates were maintained from weeks 16–112 in week 16 pasi 75 responders (figure 7) figure 4. pasi 75 response from week 52 in all patients with continuous deucravacitinib treatment for up to 112 weeks 80.4% 84.0% 80.4% 84.4% 80.2% 82.4% 0 20 40 60 80 100 52 56 60 64 68 72 76 80 84 88 92 96 100 104 108 112 treatment week from day 1 in poetyk pso-1 patients, n 262mnri 262 262 262 262 262 262 262 265 tfr 265 as observed 259 259 257 257 253 253 258 258 250 251 237 238 237 238 pasi 75 start of lte deucravacitinib (tfr)deucravacitinib (as observed) deucravacitinib (mnri) r e sp o n se r at e , % lte, long-term extension; mnri, modified nonresponder imputation; pasi 75, ≥75% reduction from baseline in psoriasis area and severity index; tfr, treatment failure rules. figure 5. maintenance of pasi 75 response in week 16 pasi 75 responders with continuous deucravacitinib treatment for up to 112 weeks 0 10 20 30 40 50 60 70 80 90 100 treatment week from day 1 in poetyk pso-1 patients, n mnri tfr as observed start of lte 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84 88 92 96 100 104 108 112 173 171 173 167 171 167 169 171 169 166 171 166 169 171 169 165 171 165 160 171 160 160 171 160 165 171 165 169 171 169 169 171 169 164 171 164 166 171 166 172 171 172 170 171 170 173 171 173 173 171 173 100% 90.2% 91.3%100% 90.2% 91.3%100% 90.1% 91.0% r e sp o n se r at e , % deucravacitinib (tfr)deucravacitinib (as observed) deucravacitinib (mnri) pasi 75 lte, long-term extension; mnri, modified nonresponder imputation; pasi 75, ≥75% reduction from baseline in psoriasis area and severity index; tfr, treatment failure rules. figure 6. pasi 90 response from week 52 in all patients with continuous deucravacitinib treatment for up to 112 weeks 0 10 20 30 40 50 60 70 80 90 100 52 56 60 64 68 72 76 80 84 88 92 96 100 104 108 112 treatment week from day 1 in poetyk pso-1 patients, n mnri tfr as observed start of lte 54.3% 56.7%54.3% 57.0% 54.2% 55.2% 265 265 259 259 257 257 253 253 258 258 250 251 237 238 237 238 262 262 262 262 262 262 262 262 r e sp o n se r at e , % deucravacitinib (tfr)deucravacitinib (as observed) deucravacitinib (mnri) pasi 90 lte, long-term extension; mnri, modified nonresponder imputation; pasi 90, ≥90% reduction from baseline in psoriasis area and severity index; tfr, treatment failure rules. figure 7. maintenance of pasi 90 response in week 16 pasi 75 responders with continuous deucravacitinib treatment for up to 112 weeks 0 10 20 30 40 50 60 70 80 90 100 treatment week from day 1 in poetyk pso-1 patients, n mnri tfr as observed start of lte 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84 88 92 96 100 104 108 112 173 171 173 167 171 167 169 171 169 166 171 166 169 171 169 165 171 165 160 171 160 160 171 160 165 171 165 169 171 169 169 171 169 164 171 164 166 171 166 172 171 172 170 171 170 173 171 173 173 171 173 63.0% 65.3% 63.1%63.0% 65.3% 63.1%62.6% 64.9% 63.0% r e sp o n se r at e , % deucravacitinib (tfr)deucravacitinib (as observed) deucravacitinib (mnri) pasi 90 lte, long-term extension; mnri, modified nonresponder imputation; pasi 75/90, ≥75%/≥90% reduction from baseline in psoriasis area and severity index; tfr, treatment failure rules. spga 0/1 outcomes • overall, spga 0/1 responses were consistent from weeks 52–112 (figure 8) • spga 0/1 responses were maintained from weeks 16–112 in week 16 pasi 75 responders (figure 9) figure 8. spga 0/1 response from week 52 in all patients with continuous deucravacitinib treatment for up to 112 weeks 0 10 20 30 40 50 60 70 80 90 100 52 56 60 64 68 72 76 80 84 88 92 96 100 104 108 112 treatment week from day 1 in poetyk pso-1 patients, n mnri tfr as observed start of lte 265 265 259 259 257 257 253 253 258 258 250 251 237 238 237 238 262 262 262 262 262 262 262 262 66.0% 67.6% 66.0% 67.9% 65.6% 66.5% r e sp o n se r at e , % deucravacitinib (tfr)deucravacitinib (as observed) deucravacitinib (mnri) spga 0/1 lte, long-term extension; mnri, modified nonresponder imputation; spga 0/1, static physician’s global assessment score of 0 (clear) or 1 (almost clear) with a ≥2-point improvement from baseline; tfr, treatment failure rules. figure 9. maintenance of spga 0/1 response in week 16 pasi 75 responders with continuous deucravacitinib treatment for up to 112 weeks 0 10 20 30 40 50 60 70 80 90 100 treatment week from day 1 in poetyk pso-1 patients, n mnri tfr as observed start of lte 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84 88 92 96 100 104 108 112 84.4% 74.0% 73.1% 84.4% 74.0% 73.1%84.2% 73.7% 73.5% 173 171 173 167 171 167 169 171 169 166 171 166 169 171 169 165 171 165 160 171 160 160 171 160 165 171 165 169 171 169 169 171 169 164 171 164 166 171 166 172 171 172 170 171 170 173 171 173 173 171 173 r e sp o n se r at e , % deucravacitinib (tfr)deucravacitinib (as observed) deucravacitinib (mnri) spga 0/1 lte, long-term extension; mnri, modified nonresponder imputation; spga 0/1, static physician’s global assessment score of 0 (clear) or 1 (almost clear) with a ≥2-point improvement from baseline; tfr, treatment failure rules. conclusions • continuous treatment with deucravacitinib for up to 112 weeks resulted in durable efficacy — high efficacy responses in patients from the poetyk pso-1 study who received continuous deucravacitinib from day 1 to week 52 have been previously reported3 — clinical outcomes were consistent from weeks 52–112 in these patients who entered the poetyk lte — clinical efficacy responses were maintained well through week 112 among those who achieved pasi 75 at week 16 with deucravacitinib treatment • deucravacitinib, a once-daily oral drug, has the potential to become a treatment of choice and new standard of care for patients who require systemic therapy for their moderate to severe plaque psoriasis references 1. burke jr, et al. sci transl med. 2019;11:eaaw1736. 2. sotyktu™ (deucravacitinib) [package insert]. princeton, nj, usa; bristol-myers squibb company; september 2022. 3. wrobleski st, et al. j med chem. 2019;62:8973–8995. 4. armstrong aw, et al. j am acad dermatol. 2023;88:29-39. 5. strober b, et al. j am acad dermatol. 2023;88:40-51. 6. armstrong a, et al. presented at the annual meeting of the aad; april 23–25, 2021.7. warren rb, et al. presented at the 30th eadv congress; september 29–october 2, 2021. 8. warren rb, et al. presented at the eadv spring symposium; may 12–14, 2022. 9. reich k, et al. br j dermatol. 2021;185:1146–1159. 10. papp k, et al. br j dermatol. 2021;185:1135–1145. acknowledgments • this study was sponsored by bristol myers squibb • writing and editorial assistance was provided by liz rockstein, phd, of peloton advantage, llc, an open health company, parsippany, nj, usa, funded by bristol myers squibb • the authors also acknowledge julie scotto, bs, mph, for her contributions to this analysis disclosures • ml: research funds on behalf of mount sinai: abbvie, amgen, arcutis, avotres, boehringer ingelheim, dermavant, eli lilly, incyte, janssen, ortho dermatologics, regeneron, and ucb; consultant: aditum bio, almirall, altrubio, anaptysbio, arcutis, arena, aristea, arrive technologies, avotres, biomx, boehringer ingelheim, brickell biotech, bristol myers squibb, cara therapeutics, castle biosciences, corevitas’ (corrona) psoriasis registry, dermavant, dr. reddy’s laboratories, evelo biosciences, evommune, forte biosciences, helsinn therapeutics, hexima, leo pharma, meiji seika pharma, mindera, pfizer, seanergy, and verrica • rbw: research grants: abbvie, almirall, amgen, celgene, janssen, eli lilly, leo pharma, novartis, pfizer, and ucb; consulting fees: abbvie, almirall, amgen, astellas, boehringer ingelheim, celgene, dice therapeutics, eli lilly, glaxosmithkline, janssen, leo pharma, novartis, pfizer, sanofi, ucb, union, and xenoport • hs: clinical investigator: abbvie, amgen, boehringer ingelheim, bristol myers squibb, eli lilly, janssen, leo pharma, novartis, and sun pharma • si: grants and personal fees: abbvie, eisai, kyowa kirin, janssen, leo pharma, maruho, sun pharma, taiho yakuhin, tanabe mitsubishi, and torii yakuhin; personal fees: amgen (celgene), boehringer ingelheim, bristol myers squibb, daiichi sankyo, eli lilly, novartis, and ucb • cp: grants and consultant: abbvie, almirall, amgen, boehringer ingelheim, bristol myers squibb, celgene, eli lilly, janssen, leo pharma, merck, mylan, novartis, pfizer, sandoz, and ucb • jcs: advisory board member/consultant: abbvie, leo pharma, novartis, pierre-fabre, sanofi genzyme, and trevi; speaker: abbvie, eli lilly, janssen-cilag, leo pharma, novartis, and sanofi genzyme; investigator: abbvie, amgen, bristol myers squibb, galapagos, galderma, incyte, infrarx, janssen-cilag, menlo therapeutics, merck, novartis, pfizer, regeneron, ucb, and trevi • ls: consultant, paid investigator, and/or speaker: abbvie, amgen, anacor, ascend, astellas, astrazeneca, blaze bioscience, bristol myers squibb, boehringer ingelheim, botanix, celgene, dermira, eli lilly, galderma, genentech, glaxosmithkline, hexima, janssen, leo pharma, mayne, medimmune, merck (msd), merck-serono, novartis, otsuka, pfizer, phosphagenics, photon md, regeneron, roche, samumed, sanofi genzyme, shr, sun pharma anz, trius, ucb, and zai lab • tp: advisory board and consulting fees: abbvie, almirall, amgen, boehringer ingelheim, bristol myers squibb, celgene, eli lilly, galderma, incyte, janssen, leo pharma, novartis, pfizer, sanofi genzyme, sun pharma, and ucb • ec, lh, an, rmk, and sb: employees and shareholders: bristol myers squibb • am: advisory board: abbott labs, amgen, boehringer ingelheim, janssen biotech, leo pharma; consultant: abbott labs, amgen, eli lilly, janssen biotech, leo pharma, novartis, sun pharma, and ucb; honoraria: abbott labs, amgen, boehringer ingelheim, eli lilly, janssen biotech, leo pharma, novartis, sun pharma, and ucb; investigator: abbott labs, amgen, boehringer ingelheim, celgene, eli lilly, janssen biotech, leo pharma, merck, novartis, sun pharma, and ucb; research grants: abbott labs, amgen, boehringer ingelheim, celgene, janssen biotech, leo pharma, merck, and sun pharma; speaker: abbott labs, amgen, janssen biotech, leo pharma, sun pharma, and ucb • dt: grant/research support, consultant, scientific advisory board speakers bureau: abbvie, almirall, amgen, biogen idec, boehringer ingelheim, bristol myers squibb, eli lilly, galapagos, galderma, janssen-cilag, leo pharma, novartis, pfizer, regeneron, roche, sandoz-hexal, sanofi, target solution, and ucb • ab: speaker (with honoraria): abbvie, arcutis, bristol myers squibb, eli lilly, pfizer, regeneron, sanofi, and ucb; scientific adviser (with honoraria): abbvie, abcentra, affibody, aligos, almirall, alumis, amgen, anaptysbio, arcutis, arena, aslan, athenex, bluefin biomedicine, boehringer ingelheim, bristol myers squibb, cara therapeutics, dermavant, ecor1, eli lilly, escient, evelo biosciences, evommune, forte biosciences, galderma, highlightii pharma, incyte, innoventbio, janssen, landos, leo pharma, merck, novartis, pfizer, rapt, regeneron, sanofi genzyme, spherix global insights, sun pharma, tll pharmaceutical, trialspark, ucb, vibliome, and xencor; clinical study investigator (institution has received clinical study funds): abbvie, acelyrin, almirall, amgen, arcutis, athenex, boehringer ingelheim, bristol myers squibb, concert, dermavant, eli lilly, evelo biosciences, evommune, galderma, incyte, janssen, leo pharma, merck, novartis, pfizer, regeneron, sun pharma, and ucb mailto:lebwohl%40aol.com?subject= https://creativecommons.org/licenses/by-nc-nd/4.0/ 101102042_cobi_pop_pk_l1a presented at the winter clinical dermatology conference; january 13-18, 2023; kohala coast, hawaii copies of this poster obtained through this qr code, are for your personal use only and may not be reproduced without permission from the authors. copyright © 2023. all rights reserved. background • atopic dermatitis (ad) is a chronic inflammatory skin disease associated with substantial patient burden that increases with greater disease severity1,2 – despite treatment with systemic therapies, patients with moderate or severe ad often report significantly worse outcomes than patients with mild ad, including severe itch, pain, and greater impact on quality of life • there is a need for more effective therapies in patients with moderate or severe disease • abrocitinib is an oral, once-daily, janus kinase 1–selective inhibitor approved for the treatment of adults and adolescents with moderate-to-severe ad3-5 • abrocitinib was efficacious and well tolerated in patients when administered as monotherapy or in combination with background topical therapy in multiple phase 3 clinical trials6-8 objective • to evaluate the efficacy and safety of abrocitinib in patients with moderate-to-severe ad classified by baseline disease severity methods study design and assessments • data were analyzed post hoc from clinical trials with abrocitinib administered as monotherapy (pooled phase 2b [nct02780167] and phase 3 jade mono-1 [nct03349060] and jade mono-2 [nct03575871]) or in combination with topical therapy (jade compare; nct03720470) • the study designs and assessments are shown in figure 1 figure 1. study designs and assessments • data from patients in the pooled monotherapy studies and compare study were analyzed separately • patients who received abrocitinib (200 or 100 mg) or placebo were classified by disease severity at baseline – iga score (3; 4) – easi score (≥25; <25)d – %bsa (10 to 30; >30 to 50; >50) • efficacy assessments – iga 0/1 – easi-75 • safety assessmentse – teaes in baseline iga 3 and iga 4 subgroups abrocitinib 10 mg qd (n=49) placebo qd (n=55) abrocitinib 100 mg qd (n=55) abrocitinib 200 mg qd (n=54) abrocitinib 30 mg qd (n=50)eligibility criteriaa • 18-75 years of age with ad for ≥1 year • moderate-to-severe ad (iga ≥3; easi ≥12; %bsa ≥10) m on ot he ra py p oo l c o m p a r e phase 2b placebo qd (n=131) abrocitinib 100 mg qd (n=238) abrocitinib 200 mg qd (n=226) dupilumab 300 mg q2wb,c (n=242) eligibility criteriaa • ≥18 years of age with ad for ≥1 year • moderate-to-severe ad (iga ≥3; easi ≥16; %bsa ≥10; pp-nrs ≥4) jade compare placebo qd (n=155) abrocitinib 100 mg qd (n=314) abrocitinib 200 mg qd (n=309) eligibility criteriaa • ≥12 years of age with ad for ≥1 year • moderate-to-severe ad (iga ≥3; easi ≥16; %bsa ≥10; pp-nrs ≥4) jade mono-1 jade mono-2 0 2 4 8 time (weeks) 12 16 %bsa, percentage of body surface area; ad, atopic dermatitis; easi, eczema area and surface index; easi-75, ≥75% improvement on the easi; iga, investigator’s global assessment; iga 0/1, iga score of 0 (clear) or 1 (almost clear) with a ≥2-point improvement from baseline; iga 3, iga score of 3 (moderate); iga 4, iga score of 4 (severe); pp-nrs, peak pruritus numerical rating scale (used with permission from regeneron pharmaceuticals, inc., and sanofi); q2w, once every 2 weeks; qd, once daily; teae, treatment-emergent adverse event. ainadequate response or intolerance to topical medication or requirement for systemic therapy to control ad. bactive control arm; data not included in this analysis. cafter a 600-mg loading dose of subcutaneous duplilumab. dthe mean baseline easi score for the monotherapy pool was 25. ethe safety analysis also included patients from the jade regimen (nct03627767; open-label phase) and jade extend (nct03422822; april 2020 data cut) studies. short-term efficacy and safety of abrocitinib by baseline disease severity in patients with moderate-to-severe atopic dermatitis zakiya p. rice,1 melinda j. gooderham,2 mark g. lebwohl,3 eric l. simpson,4 mark boguniewicz,5 andreas wollenberg,6 irina lazariciu,7 gary l. chan,8 justine alderfer,9 melissa watkins10 1dermatology associates of georgia, atlanta, ga, usa; 2skin centre for dermatology, queen’s university and probity medical research, peterborough, on, canada; 3department of dermatology, icahn school of medicine at mount sinai, new york, ny, usa; 4department of dermatology, oregon health & science university, portland, or, usa; 5department of pediatrics, national jewish health and university of colorado school of medicine, denver, co, usa; 6ludwig maximilian university, munich, germany; 7department of biostatistics, iqvia, qc, canada; 8pfizer inc., groton, ct, usa; 9pfizer inc., collegeville, pa, usa; 10pfizer inc., new york, ny, usa results efficacy • in both the jade monotherapy and the jade compare populations, a greater proportion of patients achieved iga 0/1 or easi-75 responses with abrocitinib 200 mg and abrocitinib 100 mg compared with placebo at week 12 across all subgroups of disease severity as classified by baseline iga or easi scores (figure 2) figure 2. efficacy at week 12 in baseline disease severity subgroups by iga and easi scores placebo abrocitinib 100 mg abrocitinib 200 mg placebo abrocitinib 100 mg abrocitinib 200 mg 10 30 48 4 22 30 20 43 48 2 25 49 14 50 69 10 35 56 35 64 62 54 75 21 90 80 30 0 40 50 10 60 70 20 jade monotherapy iga 4iga 3 127n 226 228 78 139 128 85 151 133 43 84 86 iga 4iga 3 p at ie nt s, % (9 5% c i) iga 0/1 response jade compare 90 80 30 0 40 50 10 60 70 20 jade monotherapy easi ≥25easi <25 109n 173 184 96 192 171 58 113 82 70 122 137 easi ≥25easi <25 p at ie nt s, % (9 5% c i) easi-75 response jade compare iga, investigator’s global assessment; iga 0/1, iga score of 0 (clear) or 1 (almost clear) with a ≥2-point improvement from baseline; iga 3, iga score of 3 (moderate); iga 4, iga score of 4 (severe). • in the subgroups classified by %bsa (percentage of body surface area), a greater proportion of patients achieved iga 0/1 response with abrocitinib 200 mg and abrocitinib 100 mg than placebo at week 12 (figure 3) • in the jade monotherapy population, efficacy responses occurred in a dose-dependent manner across all subgroups of baseline disease severity (figures 2 and 3) figure 3. efficacy at week 12 in baseline disease severity subgroups by %bsa 10 40 55 12 28 47 3 17 26 43 36 17 17 43 50 28 53 9 90 80 30 0 40 50 10 60 70 20 jade monotherapy %bsa >30-50%bsa 10-30 60n 89 104 65 125 114 80 151 138 29 63 50 41 73 66 57 99 103 %bsa 10-30%bsa >50 %bsa >50%bsa >30-50 p at ie nt s, % (9 5% c i) iga 0/1 response jade compare placebo abrocitinib 100 mg abrocitinib 200 mg %bsa, percentage of body surface area; iga 0/1, investigator’s global assessment score of 0 (clear) or 1 (almost clear) with a ≥2-point improvement from baseline. safety • overall treatment-emergent adverse events (aes) were similar in both the baseline iga 3 and iga 4 subgroups – the rates of serious aes, severe aes, and aes leading to discontinuation were also similar • the incidence rates for serious infections were similar in both subgroups and had widely overlapping confidence intervals (table 1) • the incidence rates for all herpes zoster infections was higher in the iga 4 subgroup than the iga 3 subgroup (table 1) • no meaningful differences were seen in laboratory values of interest between the 2 subgroups table 1. safety in baseline disease severity subgroups by iga score aes of special interest (per 100 py) iga 3 n=1753 iga 4 n=1103 serious infections 2.18 2.88 herpes zoster infectionsa 2.49 4.93 ae, adverse event; py, person-years. athe hazard ratio for iga=4 over iga=3 obtained in a multivariate analysis using a cox regression model was significantly greater than 1. conclusions • abrocitinib, used as monotherapy or in combination with topical therapy, provided clinically meaningful improvements in patients with ad across various subgroups of baseline disease severity • a greater proportion of patients achieved iga 0/1 or easi-75 with abrocitinib versus placebo at week 12 across all subgroups of disease severity classified by baseline iga score, baseline easi score, or %bsa at baseline • efficacy responses were dose dependent across all subgroups of baseline disease severity in the pooled monotherapy population • aes were similar in both the iga 3 and iga 4 baseline disease severity subgroups, with no unexpected safety signals references 1. simpson et al. j am acad dermatol. 2016;74:491-498. 2. simpson et al. jama dermatol. 2018;154:903-912. 3. cibinqo (abrocitinib). prescribing information. pfizer ltd.; september 2021. 4. cibinqo (abrocitinib). summary of product characteristics. pfizer europe; october 2022. 5. cibinqo (abrocitinib). prescribing information. pfizer labs; january 2022. 6. simpson el et al. lancet. 2020;396:255-266. 7. silverberg ji et al. jama dermatol. 2020;156:863-873. 8. bieber t et al. n engl j med. 2021;384:1101-1112. acknowledgments editorial/medical writing support under the guidance of authors was provided by amanda mabhula, phd, and renata cunha, pharmd, at apothecom, san francisco, ca, usa, and was funded by pfizer inc., new york, ny, usa, in accordance with good publication practice (gpp 2022) guidelines (ann intern med. 2022; 10.7326/ m22-1460). this analysis was sponsored by pfizer inc. previously presented at the international society of atopic dermatitis (isad); october 17-19, 2022; montréal, québec, canada disclosures zpr is an advisory board member for pfizer inc., biotech, cassiopeia, and medscape; a consultant for pfizer inc., brickell biotech, cassiopeia, dermira, and regeneron pharmaceuticals/sanofi; has received funding from anacor pharmaceuticals, celgene, galderma, regeneron/sanofi genzyme, merck & co., and abbvie; and has been a speaker for pfizer inc., dermira, the international hyperhidrosis society, prime, and regeneron pharmaceuticals/sanofi. mjg has received grants, personal fees, honoraria, and/or nonfinancial support from pfizer inc., abbvie, amgen, akrospharma, arcutis, bristol myers squibb, boehringer ingelheim, celgene, dermira, eli lilly and company, galderma, janssen, kyowa kirin, leo pharma, medimmune, merck, novartis, roche, sanofi genzyme, regeneron, sun pharma, ucb, bausch health (valeant), aslan, dermavant and meiji. mgl is an employee of mount sinai and receives research funds from abbvie, amgen, arcutis, avotres, boehringer ingelheim, cara therapeutics, dermavant sciences, eli lilly and company, incyte, janssen research & development, llc, ortho dermatologics, regeneron, and ucb, inc. and is a consultant for pfizer inc., aditum bio, almirall, altrubio inc., anaptysbio, arcutis, inc., arena pharmaceuticals, aristea therapeutics, arrive technologies, avotres therapeutics, biomx, brickell biotech, boehringer ingelheim, bristol myers squibb, cara therapeutics, castle biosciences, corevitas, dermavant sciences, dr. reddy’s laboratories, evelo biosciences, evommune, inc., facilitation of international dermatology education, forte biosciences, foundation for research and education in dermatology, helsinn therapeutics, hexima ltd., leo pharma, meiji seika pharma, mindera, seanergy, and verrica. els has received grants from pfizer inc., eli lilly and company, kyowa kirin, leo pharma, merck, and regeneron and personal fees from pfizer inc., bausch health (valeant), dermira, eli lilly and company, galderma, leo pharma, menlo therapeutics, novartis, regeneron, and sanofi-genzyme. mb has been an investigator for regeneron and incyte and an advisor for pfizer inc., abbvie, eli lilly and company, incyte, janssen, leo pharma, regeneron, and sanofi genzyme. aw has been an advisor, speaker, or investigator for pfizer inc., almirall, beiersdorf, bioderma, chugai, galapagos, galderma, hans karrer, leo pharma, eli lilly and company, l’oreal, maruho, medimmune, novartis, pierre fabre, regeneron, santen, and sanofi. il is an employee of iqvia, who were paid contractors to pfizer inc. in the development of this poster and in providing statistical support. glc, ja, and mw are employees and shareholders of pfizer inc. acknowledgements: medical writing support was provided by prescott medical communications group (chicago, il) with financial support from ortho dermatologics | presented at the fall clinical dermatology conference • october 17-20, 2019 • las vegas, nv synopsis ◾ psoriasis treatment includes both topical and systemic therapies, with treatment type selected based on a variety of considerations—including disease severity, patient preference, and efficacy ◾ topicals are considered first-line therapy for mild disease1 and systemic therapies may be useful in patients with more severe disease; however, topical treatments are having an increasing role in moderate-to-severe psoriasis as an integral part of combination therapy ◾ recently, a novel halobetasol propionate 0.01%/tazarotene 0.045% (hp/taz) lotion formulation has demonstrated efficacy versus vehicle for the treatment of moderate or severe plaque psoriasis,2, 3 and the combination of these two agents in this formulation demonstrated a synergistic benefit4 ◾ no direct comparative studies have been conducted between hp/taz and systemic therapies such as apremilast (otezla®), an oral treatment approved in patients with moderate-to-severe plaque psoriasis objectives ◾ to evaluate efficacy of a once-daily fixed combination of hp/taz lotion compared with vehicle in a subgroup of patients with moderate plaque psoriasis ◾ to place hp/taz results in context with published data from the oral treatment apremilast5 methods ◾ this analysis was a pooled post hoc analysis of two phase 3, multicenter, double-blind, vehicle-controlled studies (nct02462070 and nct02462122)2 ◾ participants in the phase 3 studies were randomized (2:1) to receive hp/taz or vehicle lotion once-daily for 8 weeks, with a 4-week posttreatment follow-up ◾ analyses were conducted in a subset of participants with a baseline investigator global assessment (iga) score of 3 (moderate) and body surface area (bsa) 5-10% ◾ efficacy assessments included: • mean percent change from baseline in 5-point igaxbsa scores • percentage of participants with a ≥75% reduction in mean igaxbsa (igaxbsa-75) ◾ the subgroup population analyzed in these post hoc analyses aligns closely with the population analyzed in a published phase 4 study of oral apremilast5 • in this apremilast study, patients with a static physician’s global assessment (pga) score=3 were randomized (2:1) to twice-daily active treatment or placebo for 16 weeks; assessments included the 6-point pgaxbsa and pgaxbsa-75 results ◾ this analysis included 163 participants in the hp/taz study (hp/taz, n=100; vehicle, n=63) and 221 participants in the apremilast study (apremilast, n=148; placebo, n=73) ◾ age, sex, and mean baseline bsa and igaxbsa scores in the hp/taz analysis population were similar to those enrolled in the apremilast study (table 1) table 1: baseline demographics and disease characteristics (itt population) hp/taz pooled analysis apremilast studya hp/taz (n=100) vehicle (n=63) apremilast (n=148) placebo (n=73) age, mean (sd), years 49.4 (15.7) 50.9 (14.9) 48.6 (15.4) 51.1 (13.7) male, n (%) 63 (63.0) 38 (60.3) 74 (50.0) 41 (56.2) igaxbsa score, mean (sd)b 20.9 (5.0) 18.7 (4.3) 21.8 (5.3) 21.6 (5.9) bsa, mean (sd) 7.0 (1.7) 6.2 (1.4) 7.2 (1.6) 7.1 (1.8) dlqi total score, mean (sd) 7.2 (5.4) 8.4 (5.8) 11.0 (6.5) 11.1 (6.5) astrober et al. 2017.5 bassessment was pgaxbsa in apremilast study bsa, body surface area; dlqi, dermatology life quality index; hp/taz, halobetasol propionate 0.01% and tazarotene 0.045%; iga, investigator global assessment; itt, intent-to-treat; pga, physician’s global assessment. efficacy of halobetasol 0.01%/tazarotene 0.045% (hp/taz) fixed combination in the treatment of moderate plaque psoriasis: indirect comparison between pooled phase 3 trials of hp/taz and oral treatment (apremilast) brad glick, do, mph1; edward lain, md, mba2; tina lin, pharmd3; robert israel, md4 1gsi clinical research, margate, fl; 2austin institute for clinical research, austin, tx; 3ortho dermatologics, bridgewater, nj; 4bausch health, bridgewater, nj ◾ at week 8, hp/taz-treated participants had a 46% mean reduction from baseline in igaxbsa scores compared with a 16% reduction in vehicle-treated participants (p<0.001; figure 1 and figure 3a) • this effect was sustained during the 4-week posttreatment period, with a 40% reduction from baseline in igaxbsa score with hp/taz at the end of 12 weeks (figure 1) figure 1: mean percent reduction from baseline in igaxbsa score by study visit (itt population) -60% -50% -40% -30% -20% -10% 0% study visit (weeks) m e a n p e rc e n t c h a n g e f ro m b a se lin e baseline 2 4 6 8 12 treatment posttreatment hp/taz (n=100) vehicle (n=63) **p<0.001 vs vehicle (=0.001 at week 12). bsa, body surface area; hp/taz, halobetasol propionate 0.01% and tazarotene 0.045%; iga, investigator global assessment; itt, intent-to-treat. ◾ the percentage of participants with a ≥75% reduction from baseline igaxbsa at week 8 was significantly higher following treatment with hp/taz lotion (33.0%) compared with vehicle (9.5%; p<0.001; figure 2 and figure 3b) figure 2: percentage of patients with ≥75% reduction from baseline in igaxbsa (itt population) 0% 15% 10% 5% 20% 25% 30% 35% 40% 45% 50% study visit (weeks) p e rc e n ta g e o f p a rt ic ip a n ts baseline 2 4 6 8 12 treatment posttreatment hp/taz (n=100) vehicle (n=63) *p<0.01; **p<0.001 vs vehicle. bsa, body surface area; hp/taz, halobetasol propionate 0.01% and tazarotene 0.045%; iga, investigator global assessment; itt, intent-to-treat. ◾ these hp/taz results align closely with those from the apremilast study • apremilast-treated participants had a 48% mean reduction from baseline in pgaxbsa scores at week 16 compared with a 10% reduction in placebo-treated participants (p<0.0001; figure 3a) • the percentage of participants achieving a ≥75% reduction from baseline in igaxbsa score was 35.1% in the apremilast group versus 12.3% in the placebo group (p<0.001; figure 3b) figure 3: indirect comparison between hp/taz and apremilast -50% -40% -30% -20% -10% 0% hp/taz (n=100) vehicle (n=63) m e an p e rc e n t c h an g e f ro m b as e lin e week 8 -46.0% -48.1% -15.7% -10.2% a. mean reduction from baseline in igaxbsaa or pgaxbsab (itt populations) -50% -40% -30% -20% -10% 0% apremilast (n=148) placebo (n=73) week 16 0% 10% 20% 30% 40% 50% hp/taz (n=100) vehicle (n=63) p e rc e n ta g e o f p ar ti ci p an ts week 8 33.0% 35.1% 9.5% 12.3% b. percentage of patients with ≥75% reduction in igaxbsaa or pgaxbsab (itt populations) apremilast (n=148) placebo (n=73) week 16 0% 10% 20% 30% 40% 50% **p<0.001 vs vehicle/placebo. ahp/taz pooled phase 3 data. bapremilast data from strober et al. 2017.5 bsa, body surface area; hp/taz, halobetasol propionate 0.01% and tazarotene 0.045%; iga, investigator global assessment; itt, intent-to-treat; pga, physician’s global assessment. conclusion ◾ in patients with moderate plaque psoriasis (iga score of 3 and bsa 5-10%), hp/taz lotion provides significantly greater efficacy than vehicle, an effect that was sustained posttreatment ◾ these week 8 results with hp/taz lotion align closely with week 16 results from a study of the oral psoriasis treatment apremilast in a similar patient population references 1. menter, et al. j am acad dermatol. 2009;60(4):643-659. 2. gold ls, et al. j am acad dermatol. 2018;79(2):287-293. 3. sugarman jl, et al. j drugs dermatol. 2018;17(8):855-861. 4. kircik lh, et al. j drugs dermatol. 2019;18(3):279-284. 5. strober b, et al. j drugs dermatol. 2017;16(8):801-808. author disclosures dr. brad glick has served as investigator, advisor, and/or speaker for abbvie, celgene, janssen, sun pharma, lilly, novartis, dermira, sanofi/genzyme, regeneron, pfizer, dermavant, chemocentryx, and ortho dermatologics. he is a stockholder in top md. dr. edward lain has nothing to disclose. dr. tina lin is an employee of ortho dermatologics. dr. robert israel is an employee of bausch health. malignancy events in patients with a history of cancer in clinical studies of brodalumab alice gottlieb,1 mark lebwohl,1 april armstrong,2 robert j. israel,3 abby jacobson4 1icahn school of medicine at mount sinai, new york, ny; 2university of southern california, los angeles, ca; 3bausch health us, llc, bridgewater, nj; 4ortho dermatologics (a division of bausch health us, llc), bridgewater, nj 2020 winter clinical dermatology conference hawaii® • january 17-22, 2020 • kohala coast, hi introduction • brodalumab is a fully human anti–interleukin-17 receptor a monoclonal antibody efficacious for the treatment of adults with moderate-to-severe plaque psoriasis • in a previous analysis, rates of malignancy among brodalumab-treated patients in clinical studies of psoriasis were generally low, and there was no increase in malignancy events with brodalumab compared with ustekinumab through 52 weeks1 objective • this exploratory analysis examined malignancy events occurring among patients with a history of malignancy in clinical studies of brodalumab in moderate-tosevere plaque psoriasis methods • patients with active malignancy or a history of malignancy within 5 years were excluded from the phase 3 brodalumab clinical program, except for those with treated and cured cutaneous squamous or basal cell carcinoma, in situ cervical cancer, or in situ breast ductal carcinoma. this analysis included patients in clinical trials of brodalumab with a history of malignancy in accordance with the above criteria • all adverse events (aes) in the neoplasms benign, malignant, and unspecified (including cysts and polyps) system organ class were reviewed, and events were adjudicated for confirmation • results are reported for patients who received placebo, ustekinumab, brodalumab 210 mg every 2 weeks (q2w), and any dose of brodalumab results • at study baseline, 2% to 3% of patients across treatment groups reported a history of malignancy (table 1) – of patients who had a prior malignancy, the most common malignancy types across treatment groups included basal cell carcinoma, squamous cell carcinoma, breast cancer, malignant melanoma, and thyroid neoplasm • of patients with prior malignancy, 35% to 61% of patients across treatment groups reported prior treatment with psoralen and ultraviolet a or ultraviolet b therapy (placebo [n=18], 61.1%; ustekinumab [n=17], 35.3%; brodalumab 210 mg q2w [n=34], 47.1%; any dose of brodalumab [n=69], 43.5%) • one patient in the brodalumab 210 mg q2w group with a history of resolved basal cell carcinoma experienced an adjudicated malignancy event of squamous cell carcinoma during the 12-week induction phase (figure 1) • through 52 weeks, 3 adjudicated malignancy events, also classified as nonmelanoma skin cancer aes (1 basal cell carcinoma, 2 squamous cell carcinoma), were reported in patients with malignancy history who received constant brodalumab 210 mg q2w (figure 2) • of patients with history of malignancy who received continuous ustekinumab, 2 adjudicated malignancy events (both basal cell carcinoma) occurred through 52 weeks, which were also classified as nonmelanoma skin cancer aes • a limitation of this study was the relatively low number of patients included in the analysis acknowledgments: this study was sponsored by ortho dermatologics. medical writing support was provided by medthink scicom and funded by ortho dermatologics. ortho dermatologics is a division of bausch health us, llc. reference: 1. lebwohl et al. poster presented at: fall clinical dermatology conference; october 18-21, 2018; las vegas, nv. conclusions • few events of malignancy occurred in patients with a history of malignancy, and there was limited evidence of malignancy recurrence through 52 weeks • longer follow-up and real-world evidence are needed to fully characterize the long-term risk of malignancy with brodalumab © 2020. all rights reserved. table 1. summary of most common prior malignancies for patients in the brodalumab clinical trials 14.9 14.9 0 14.5 4.8 9.7 0 5 10 15 20 25 adjudicated malignancies basa cell carcinoma squamous cell carcinoma ustekinumab (n=17; 13.4 py) brodalumab 210 mg q2w (n=29; 20.7 py) adjudicated malignancies ex po su re -a dj us te d ra te p er 10 0 pa ti en tye ar s (n /p y × 1 00 ) figure 2. teaes through week 52 in patients with prior malignancy.a 0 0 0 00 0 0 0 13.4 0 0 13.4 19.6 6.5 6.5 6.5 0 5 10 15 20 25 30 35 40 45 50 all neoplasms fibrous histiocytoma seborrhoeic keratosis squamous cell carcinoma placebo (n=18; 4.1 py) ustekinumab (n=17; 3.9 py) brodalumab 210 mg q2w (n=34; 7.5 py) any dose of brodalumab (n=69; 15.3 py) 584.4 509.4 721.7 647.1 0 100 200 300 400 500 600 700 800 all teaes ex po su re -a dj us te d ra te p er 10 0 pa ti en tye ar s (n /p y × 1 00 ) ex po su re -a dj us te d ra te p er 10 0 pa ti en tye ar s (n /p y × 1 00 ) neoplasmsb a b figure 1. teaes (a) and neoplasms (b) through week 12 in patients with prior malignancy.a amultiple occurrences of the same event for a patient are counted as multiple events. py, total patient-years of exposure through week 52; q2w, every 2 weeks; teae, treatment-emergent adverse event. amultiple occurrences of the same event for a patient are counted as multiple events. bincludes benign, malignant, and unspecified neoplasms (including cysts and polyps). py, total patient-years of exposure through week 12; q2w, every 2 weeks; teae, treatment-emergent adverse event. placebo (n=879) ustekinumab (n=613) brodalumab 210 mg q2w (n=1496) any dose of brodalumab (n=3066) prior malignancies 18 (2.0) 17 (2.8) 34 (2.3) 69 (2.2) basal cell carcinoma 4 (0.5) 8 (1.3) 11 (0.7) 25 (0.8) squamous cell carcinomaa 5 (0.6) 4 (0.6) 7 (0.5) 13 (0.4) breast cancer 4 (0.5) 0 (0) 4 (0.3) 6 (0.2) malignant melanoma 0 (0) 1 (0.2) 4 (0.3) 6 (0.2) thyroid neoplasm 0 (0) 0 (0) 2 (0.1) 5 (0.2) values are the number (percentage). aincludes squamous cell carcinoma of the skin. 2019_fallclinical_ct013_final.cdr a randomized, double blind, vehicle-controlled multicenter phase iii study to evaluate the safety and efficacy of bf-200 ala and narrowband red light in the treatment of superficial basal cell carcinoma (sbcc) with photodynamic therapy (pdt) 4 5 6 7 8 9 10 11 3 14 authors: v. laquer , s. bruce , t. schlesinger , n. zeitouni , a. torres , j. cohen , j. tu , w. hanke , m. goldman , d. ozog , o. markowitz , m. gold , m. nestor , b. berman , g. munavalli , d. pariser 1 2 3 12 1 13 15 trial protocol actinic keratosis 1 leiter u, garbe c. epidemiology of melanoma and nonmelanoma skin cancerthe role of sunlight. adv exp med biol. 2008;624:89-103. 2 roozeboom mh, arits ah, nelemans pj, kelleners-smeets nw. overall treatment success after treatment of primary superficial basal cell carcinoma: a systematic review and meta-analysis of randomized and nonrandomized trials. cancer res. 2003; 15;63(8):1727-30. 3 walling hw, fosko sw, geraminejad pa, whitaker dc, arpey cj. aggressive basal cell carcinoma: presentation, pathogenesis, and management.cancer metastasis rev. 2004 aug-dec;23(3-4):389-402. 4 goldberg lh, leis p, pham hn. basal cell carcinoma on the neck. dermatol surg. 1996 apr;22(4):349-53. 5 bichakjian ck, olencki t, aasi sz, et al. basal cell skin cancer, version 1.2016, nccn clinical practice guidelines in oncology. j natl compr canc netw. 2016 may;14(5):574-97. 6 martin i, schaarschmidt ml, glocker a, herr r, schmieder a, goerdt s, peitsch wk. patient preferences for treatment of basal cell carcinoma: importance of cure and cosmetic outcome. acta derm venereol. 2016 mar;96(3):355-60. 7 morton ca, dominicus r, radny p et al. a randomized, multinational, noninferiority, phase iii trial to evaluate the safety and efficacy of bf-200 aminolaevulinic acid gel vs. methyl aminolaevulinate cream in the treatment of nonaggressive basal cell carcinoma with photodynamic therapy. br j dermatol. 2018 aug;179(2):309-319. references objectives n ® the current pivotal phase iii study (nct03573401; recruiting), aims to demonstrate the efficacy and safety of pdt with bf-200 ala (ameluz ) ® 2 performed with the narrowband, red light pdt illumination source bf-rhodoled (~635 nm; 37j/cm ) in comparison to the respective vehicle treatment for sbbc. medication n bf-200 ala gel (contains 10% ala hydrochlorid equivalent to 7.8% 5-aminolevulinic free acid (ala)) n vehicle to bf-200 ala gel patients & treatment procedure the study foresees randomization of 186 subjects at a ratio of 4:1 (drug vs. vehicle) at approximately 15 clinical sites in the us. all subjects will receive one obligatory pdt cycle with 2 pdt sessions per cycle, 1-2 weeks apart. in case of partial or no response, a second pdt cycle will be administered 3 months later. all subjects will receive surgical excision treatment of at least one lesion at the end of the last pdt cycle for histological assessment. this lesion is selected during the randomization visit and is referred to as main target lesion (mtl). after completing the dosing phase, all subjects will be followed up for 5 years. all subjects will receive excision of their main target lesion at latest at the end of the clinical observation period (visit 8) for histopathological evaluation of lesion status irrespective of the outcome of the clinical assessment. endpoints primary endpoint: n composite clinical & histological response of subject's main target lesion (mtl) as assessed 12 weeks after start of last pdt cycle selected secondary endpoints (after last pdt cycle): n clinical response rate of mtl n histological response rate of mtl n subject complete clearance of all treated lesions n investigator-related aesthetic appearance (before biopsy) synopsis basal cell carcinoma (bcc) represents the most frequent nonmelanoma skin cancer (nmsc) affecting mainly adult, fair-skinned individuals. bccs develop predominately in sun-damaged skin with an incidence rate of 1,406/100,000 in the united states (us) (1998/99), 3,252/100,000 in 1 queensland/australia (1997) and 143/100,000 in germany (2004) . incidence rates in the us dramatically increased by 50% in males and by 20% in 1 females from 1977/78 to 1998/99 . 2 other authors describe an annual increase by 3 to 10% . the average probability to develop a bcc throughout a lifetime is ~30%, whereas the risk 3 of developing additional bccs after the first one is with 44% considerably higher . based on their histology, bccs are classified as non-aggressive, low risk bccs with good to intermediate prognosis and aggressive, high-risk 3 forms with fundamentally different biological characteristics . superficial bcc (sbcc) account for 10-38% of bccs and are generally classified 4 non-aggressive or at least less aggressive subtypes . schematic overview: pdt for sbcc treatment medical need for alternative bcc treatment options visit 1 (screening ) (=4 weeks before pdt-1) visit 2 (pdt-1) visit 3 (pdt-2, 1-2 weeks post-pdt-1) application of bf-200 ala and placebo plus illumination with a narrowband red light source for 10 min visit 4 (5 weeks post -pdt-1) in case of remaining lesions after first pdt cycle, a second pdt cycle will be performed (partial or non-responders). phone call (1 week post pdt-2) visit 5 (12 weeks post -pdt-1; pdt-3) visit 6 (pdt-4, 1-2 weeks post-pdt-3) fus (12, 24, 36 and 60 months post-pdt) phone call (1 week post pdt-4) visit 7 (5 weeks post -pdt-3) visit 8 (12 weeks post pdt-3) bf-200 ala, which matches these requirements, was granted marketing approval for the treatment of superficial and nodular bcc in the european union (eu) in january 2017. this approval was primarily based on a single pivotal study that demonstrated the efficacy and safety of bf-200 ala pdt in conjunction with a narrowband red light source (~635 nm; 37 j/cm ) for the treatment of non-aggressive superficial 2 and/or nodular bcc with a thickness of <2 mm. the control group received pdt with methylaminolevulinic acid (mal) and 281 subjects were randomized at 24 sites in germany and the uk. each subject had up to 3 bccs, which were treated with 1 or 2 cycles of pdt that consisted of 2 pdts 1 week apart. all subjects entered a 5-year follow-up phase 12 weeks after their last pdt, which is still ongoing. when assessed 12 weeks after the last pdt cycle, patients that received bf-200 ala showed complete remission of 93.4% vs. 91.8% of nonaggressive bccs in patients that received mal (per protocol population). even higher clearance rates from 94.7% vs 96.4% were observed when looking exclusively at sbccs. a recurrence was observed for 6.8% of lesions treated with bf-200 ala and for 8.2% of lesions treated with mal at the 1-year follow-up . 7 according to recent guidelines, the goal of primary bcc treatment is the clearance of lesions while maintaining function as well as cosmesis . 5 currently, surgical treatment is the standard of care as it provides excellent efficacy for treating sbccs. however, it can result in scarring, often causing a high burden for patients. in addition, there are also cases where surgery is contraindicated or impractical due to e.g. a large size of the tumor or morbidity of the subject. consequently, there is a need for alternative treatments for bccs that circumvent the surgical drawbacks by providing robust clinical efficacy and favorable cosmetic outcomes, which is an important factor for treatment preference, especially if bccs are located on the head or trunk . 6 in recent years, red light photodynamic therapy (pdt) utilizing photosensitizer precursors such as aminolevulinic acid (ala), a precursor of protoporphyrin ix (ppix) has become increasingly important in treating sbccs, as pdt provides high efficacy along with low recurrence rates and an excellent cosmetic outcome . 7 pdt with bf-200 ala for bcc treatment in the eu lesion preparation (including degreasing, roughening of the skin) application of bf-200 ala or vehicle light-tight dressing; 3 h removal of remaining gel, illumination with narrowband red light source second pdt 1 week apart potential second pdt cycle fu1-4 12 months5 years assessment after 12 weeks nct03573401 this study is sponsored by biofrontera bioscience gmbh (germany). 1 2 3 institutes: first oc dermatology 17271 brookhurst st, fountain valley, ca 92708 ; suzanne bruce and associates, p.a., the center for skin research 1900 st. james place, #650 houston, tx 77056; clinical research center 4 5 of the carolinas 1364 ashley river road charleston, sc 29407, medical dermatology specialists 1331 n. 7th st. #250 phoenix, az 85006; university of florida department of dermatology 4037 nw 86th terrace rm 4115 6 7 8 gainesville, fl 32606; aboutskin research 5340 s. quebec st., #300 greenwood village, co 80111; skin search of rochester, inc 100 white spruce blvd, rochester, ny 14623 usa; laser & skin surgery center of indiana 8925 n. 9 10 11 meridian st. #200 indianapolis, in 46260; cosmetic laser dermatology 9339 genessee avenue, #300 san diego, ca 92121; henry ford medical center 3031 west grand boulevard #800 detroit, mi 48202; the narrows institute 12 13 for biomedical research and education, inc. c/o va nyhhs 800 poly place room 2-204 brooklyn, new york 11209 mail code 151; tennessee clinical research center 2000 richard jones rd, #223 nashville, tn 37215; center for 14 15 clinical and cosmetic research 2925 aventura boulevard #205 aventura, fl 33180; dermatology , laser & vein specialists of the carolinas 1918 randolph road #550 charlotte, nc 28207; virginia clinical research, inc. 6160 kempsville circle #200a norfolk, va 23502 seite 1 long-term efficacy and safety of brodalumab in patients with or without history of psoriatic arthritis: analysis of two phase 3 psoriasis studies alice gottlieb,1 alan menter,2 paul yamauchi,3 craig teller,4 george han,1 radhakrishnan pillai,5 tina lin,6 abby jacobson6 1icahn school of medicine at mount sinai, new york, ny; 2baylor scott & white, dallas, tx; 3dermatology institute & skin care center, santa monica, ca; 4bellaire dermatology, bellaire, tx; 5bausch health americas*, petaluma, ca; 6ortho dermatologics*, bridgewater, nj *bausch health americas and ortho dermatologics are divisions or affiliates of bausch health companies, inc. 39th annual fall clinical dermatology conference® for dermatologists • october 17-20, 2019 • las vegas, nv introduction • psoriatic arthritis (psa) is an inflammatory arthritis associated with psoriasis1 • brodalumab is a fully human anti–interleukin-17 receptor a monoclonal antibody approved for treatment of moderate-to-severe plaque psoriasis2 objective • to evaluate the efficacy and safety of brodalumab in a post hoc analysis of two phase 3, multicenter, randomized trials of brodalumab in patients with moderate-to-severe plaque psoriasis (amagine-2/-3; figure 1) with or without a history of psoriatic arthritis3 methods • in amagine-2/-3, 3625 patients received brodalumab, of whom 703 (19.4%) had a self-reported history of psa at baseline and 2922 (80.6%) did not • patients were initially randomized to brodalumab 140 or 210 mg every 2 weeks (q2w), ustekinumab, or placebo3 • at week 52, all patients entered a long-term extension and received brodalumab4 • this analysis included patients who received any dose of brodalumab through week 120 and patients receiving brodalumab 210 mg q2w after ustekinumab • skin clearance efficacy was measured by static physician’s global assessment (spga) and psoriasis area and severity index (pasi) • psoriasis symptom inventory (psi) and dermatology life quality index (dlqi) were also used – the psi measures the severity of 8 signs and symptoms of psoriasis (itch, redness, scaling, burning, stinging, cracking, flaking, and pain) each scored on a scale of 0 (not at all severe) to 4 (very severe), with a total score of up to 32 – a psi responder was defined as having a total score ≤8 with no item scores >1 • safety was summarized via exposure-adjusted rates of treatmentemergent adverse events (teaes) results efficacy • in an observed analysis at week 120, 74.8% of patients receiving any dose of brodalumab with a history of psa (n=329) and 79.1% without a history of psa (n=1501) had an spga score of 0 or 1 • 75% improvement in pasi from baseline (pasi 75; figure 2a), pasi 90 (figure 2b), and pasi 100 (figure 2c) responses were maintained from week 52 through 120 in those receiving any dose of brodalumab with and without a history of psa – at week 120, pasi 75 rates were 87.2% and 90.0%, pasi 90 rates were 76.0% and 78.7%, and pasi 100 rates were 57.8% and 58.0% in patients with and without a history of psa, respectively • skin clearance was also maintained at similar levels in patients with (n=105) and without (n=462) a history of psa who received brodalumab 210 mg q2w after ustekinumab – at week 120, pasi 75 rates were 86.2% and 91.3%, pasi 90 rates were 72.4% and 83.1%, and pasi 100 rates were 60.3% and 63.2% in patients with and without a history of psa, respectively psi and dlqi responses • the rates of psi and dlqi score of 0 or 1 responses were robust among brodalumab-treated patients at week 52 (the last observation time point) – the rates of psi response were 73.5% and 79.3% in patients with and without a history of psa, respectively (figure 3a) – the rates of dlqi score of 0 or 1 were 67.2% and 72.4% in patients with and without a history of psa, respectively (figure 3b) safety • across all study years, teae rates in patients receiving any dose of brodalumab with and without a history of psa were 331.9 and 292.8 per 100 patient-years, respectively (table 1) © 2019. all rights reserved. ► ► ► ► day 1 week 12 week 16 week 52 ► week 120 ustekinumab brodalumab 210 mg q2w brodalumab 210 mg q2w ustekin umabplacebo ustekin umabustekinumab brodalumab 210 mg q2w induction maintenance long-term extension week 16 inadequate responders brodalumab 210 mg q2w brodalumab 140 mg q2w brodalumab 140 mg q4w brodalumab 140 mg q8w brodalumab 140 mg q2w r 2:2:2:1 r 2:2:1:1 brodalumab 210 mg q2w (rescue) figure 1. amagine-2/-3 study design. r, randomization; q2w, every 2 weeks; q4w, every 4 weeks; q8w, every 8 weeks. 50.5 73.5 55.5 79.3 0 20 40 60 80 100 week 12 week 52 r es po nd er s, % psi response 44.7 67.2 46.5 72.4 0 20 40 60 80 100 week 12 week 52 dlqi 0/1 history of psa no history of psa 648 4952658 2098n1= 662 5492778 2354 a b figure 3. psi and dlqi 0/1 response rates in brodalumab-treated patients by history of psa subgroups. observed data analysis. error bars are the 95% confidence interval. dlqi 0/1, dermatology life quality index score of 0 or 1; psa, psoriatic arthritis; psi, psoriasis symptom inventory. table 1. exposure-adjusted rates of teaes in patients who received any dose of brodalumab history of psa (n=703, 1219.2 py) no history of psa (n=2922, 5312.3 py) all teaes, n (r) 4046 (331.9) 15,556 (292.8) grade ≥2 2202 (180.6) 8194 (154.2) grade ≥3 181 (14.8) 639 (12.0) serious aes, n (r) 117 (9.6) 364 (6.9) fatal aes, n (r)a 1 (0.1) 2 (0.0) observed data analysis. ae, adverse event; ci, confidence interval; n, number of adverse events; n, number of patients; psa, psoriatic arthritis; py, total patient-years of exposure through the end of the study; r, exposure-adjusted event rate per 100 patient-years; teae, treatment-emergent ae. athe 3 fatal aes were 1 sudden death (cause undetermined), 1 cardiac arrest (267 days on brodalumab; event occurred 7 days after last dose), and 1 accidental death (motor vehicle accident). weeks 12 24 36 52 72 84 96 108 1200 weeks 12 24 36 52 72 84 96 108 1200 91.1 91.9 history of psa no history of psa history of psa no history of psa history of psa no history of psa n1= 703 677 651 623 572 569 552 538 463 329 n1= 2922 2868 2702 2670 2442 25 31 2482 2416 2135 1501 pasi 75 90.0 87.2 a 79.4 76.0 78.7 78.7 n1= 703 677 651 623 572 569 552 538 463 329 n1= 2922 2868 2702 2670 2442 2531 2482 2416 2135 1501 pasi 90b 54.1 n1= 703 677 651 623 572 569 552 538 463 329 n1= 2922 2868 2702 2670 2442 2531 2482 2416 2135 1501 pasi 100 weeks 12 24 36 52 72 84 96 108 1200 58.0 57.8 54.2 c 0 20 40 60 80 100 r es po nd er s, % 0 20 40 60 80 100 r es po nd er s, % 0 20 40 60 80 100 r es po nd er s, % figure 2. pasi 75 (a), pasi 90 (b), and pasi 100 (c) responses through week 120 in patients who received ≥1 dose of brodalumab by history of psa subgroups. observed data analysis. error bars are the 95% confidence interval. n1, number of patients who had a valid measurement at the specified week; pasi 75, 90, and 100, psoriasis area and severity index 75%, 90%, and 100% improvement; psa, psoriatic arthritis; q2w, every 2 weeks. conclusion • skin clearance rates were maintained through week 120 in patients regardless of psa history • the data presented here suggest that brodalumab is efficacious and well tolerated in patients with and without history of psa acknowledgments: this study was sponsored by ortho dermatologics. medical writing support was provided by medthink scicom and funded by ortho dermatologics. ortho dermatologics is a division of bausch health us, llc. references: 1. gottlieb et al. j am acad dermatol. 2008;58:851-864. 2. siliq [package insert]. bridgewater, nj: valeant pharmaceuticals north america, llc; 2017. 3. lebwohl et al. n engl j med. 2015;373:1318-1328. 4. menter et al. poster presented at the 2017 fall clinical dermatology conference; october 12-15, 2017; las vegas, nv. skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 124 original research risk stratification of severely dysplastic nevi by non-invasively obtained gene expression and mutation analyses stephanie r. jackson, md phd1, burkhard jansen, md2, zuxu yao, phd2, and laura k. ferris, md phd1 1department of dermatology, university of pittsburgh, pittsburgh, pa 2dermtech, inc., la jolla, ca importance: strategies to non-invasively detect cutaneous melanoma generally focus on differentiating melanoma from non-melanoma lesions. however, given the variabilities in practice and lack of guidelines, it is important for clinicians to understand how such strategies and technologies perform on borderline lesions of uncertain clinical behavior. objective: to evaluate linc and prame gene expression and the presence of somatic mutations in braf, nras, and/or tert in severely dysplastic nevi (sdn) and to assess, how combining gene expression and mutation analyses may impact test performance. methods: one hundred three eligible skin lesions clinically suspicious for melanoma were noninvasively sampled via adhesive patches to enable genomic analyses. afterward, these same lesions were immediately surgically biopsied to enable comparisons of genomic analyses with histopathologic diagnoses rendered by a panel of three dermatopathologists. twenty-three of these lesions analyzed were deemed borderline lesions of sdn histology by at least one dermatopathologist. rna-based gene expression positivity by pigmented lesion assay (pla) analysis was defined by detectable levels of linc and/or prame. dna-based mutation positivity was defined as detection of somatic mutations in braf (non-v600e), nras, and/or the tert promoter. results: adding tert mutation analyses to pla gene expression increases the test’s sensitivity to rule out melanoma from 93% to 97% in this study. in addition, 61% of pla positive lesions that were not diagnosed as melanoma were found to have severe histologic atypia. pla-positive lesions histopathologically diagnosed as melanomas harbored tert mutations in 70% of cases while both sdn and non-melanoma lesions including nevi without severe histologic atypia harbored tert mutations in 4% of cases. braf non-v600e and nras mutations were only found in the melanoma group and adding these mutations did not further enhance the test’s sensitivity. conclusions and relevance: pla positivity increases with histologic atypia of pigmented skin lesions. combining tert mutation analyses with melanoma-associated gene expression provides additional genetic information to further non-invasively risk-stratify pigmented lesions. these findings furthermore support that pigmented lesions exist on a spectrum of genomic atypia that may prove useful in identifying borderline lesions beyond their morphological appearance. abstract skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 125 pigmented lesions sharing overlapping histologic features with conventional nevi and melanoma have been termed ‘dysplastic nevi’ (dn).1 the degree to which these lesions resemble the architectural disorder and cytologic atypia found in melanoma is used to stratify them as mildly, moderately, or severely dysplastic. overlapping histologic features and low intraand inter-observer agreement in the diagnosis of early melanoma raise concern that morphologic features of biopsied severely dysplastic nevi (sdn) may represent changes that could be diagnosed as early melanoma by some pathologists irrespective of the underlying tumor biology these changes may or may not be linked to. this challenge has resulted in the standard practice of ensuring complete removal of lesions characterized as sdn.2-4 while some melanomas do arise within dysplastic nevi, the majority do not, and some propose that routine re-excision of all sdn may not be necessary.5,6 improved ability to stratify the malignant potential in these borderline lesions could spare patients unnecessary procedures. mounting evidence suggests that the morphologic features of dn correlate with mutational or gene expression changes that may represent the earliest indicators of progression from nevus to melanoma.1 advancements in molecular testing may aid in stratifying biologic risk and help to diagnose potentially aggressive lesions earlier. the pigmented lesion assay (pla, dermtech, la jolla, ca) is a non-invasive molecular test capable of helping to diagnose melanoma early with high sensitivity, specificity, and a high negative predictive value.7,8 this test uses adhesive patches for sample collection and evaluates expression of rna transcripts encoding linc (long intergenic non-coding rna 518) and prame (preferentially expressed antigen in melanoma), both known to be overexpressed in melanoma.7,9 additionally, high-risk dna driver mutations (braf nonv600e, nras, tert) commonly found in early-stage melanoma can also be assessed using the same adhesive patch – based skin sample collection platform.2,10 combining these dna and rna risk factors enhances the ability to non-invasively detect melanoma.10 the objective of our current study was to evaluate the expression of linc, prame, and select melanoma driver mutations in clinically-challenging borderline lesions such as sdn and compare findings to lesions at both ends of the pigmented lesion spectrum where less controversy about management exists. data on 103 pigmented skin lesions clinically suspicious for melanoma (60 male and 43 female patients, median age 48 years) was collected under a protocol approved by the western-copernicus group (santee, ca) independent review board as previously described.10 epidermal lesional skin samples were obtained non-invasively using dermtech’s (la jolla, ca) adhesive patch sample collection platform to enable gene expression and mutation analyses. the same lesions were surgically biopsied immediately afterwards to establish histopathologic diagnoses for comparisons between pla gene expression results, mutational analyses, and morphological assessment. the histopathologic diagnoses were established by three dermatopathologists who agreed on the diagnoses of non-melanoma excluding sdn (n=50, nevi with no, mild, or moderate atypia as well as non-melanocytic lesions) or introduction methods skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 126 melanoma (n=30). twenty-three of the lesions analyzed were cases deemed sdn by at least one dermatopathologist reader. pla positivity was defined by presence of detectable rna transcripts encoding linc and/or prame. mutation positivity was defined as the presence of braf, nras, and / or tert promoter mutations by sanger sequencing in dna from skin lesion tissue obtained via adhesive patches. we excluded braf v600e mutations seen in common nevi. statistical significance of pla gene expression differences for the groups depicted in figure 1 was calculated using fisher’s exact test. pla gene expression test results of 103 pigmented skin lesions clinically suspicious for melanoma and sampled non-invasively via adhesive patches, melanoma hotspot driver mutation analyses from the same noninvasively obtained samples, and histopathologic diagnoses enabled by surgical biopsies of the same lesions immediately after adhesive patch sampling are summarized in table 1. we compared sdn (n=23) with thin invasive (median tumor thickness of 0.58mm) and in situ melanomas (n=30) as well as nonmelanomas excluding sdn (n=50, 38 nevi and 12 non-melanocytic pigmented lesions including 8 solar lentigines, 2 seborrheic keratoses, and 2 squamous cell carcinomas). detectable levels of linc, prame or both target genes were found in 93% of melanomas, 61% of sdn, and 34% of non-melanomas excluding sdn (figure 1). the addition of tert mutation analyses to pla gene expression increases the test’s sensitivity for melanoma to 97% in this study. pla-positive lesions histopathologically diagnosed as melanomas harbored tert mutations in 70% of cases while both sdn and nonmelanoma lesions including nevi without severe histologic atypia harbored tert mutations in 4% of cases. analyses of braf non-v600e and nras mutations did not further enhance the test’s sensitivity since the presence of these mutations overlapped with the presence of tert mutations in the melanoma cases studied (table 1). most tert-mutated cases were double positive for linc and prame detection irrespective of the histopathologic diagnosis rendered (2/3, 1/1 and 18/21 in non-melanomas excluding sdn, sdn and melanomas, respectively). only one lesion (a melanoma in situ) harbored a tert mutation in the absence of linc or prame expression. the aim of pigmented lesion examination is to identify melanoma at its earliest stages, when the highest cure rates are possible. we reported a 69% pla specificity in our initial validation work that viewed the samples analyzed in the 2 broad categories of melanoma and non-melanoma diagnoses.3,11 we now show sdn are almost twice as often positive by pla and five times more often pla double-positive than non-melanoma lesions excluding sdn also clinically suspicious of melanoma. our data furthermore demonstrate that pla combined with mutational analysis for tert driver mutations improves test sensitivity to 97% for melanoma. overlapping histopathologic diagnostic criteria between early melanoma and dysplastic nevi has prompted concern that some sdn may actually represent evolving melanomas and some argue that they results discussion skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 127 table 1. dermatopathology diagnoses, pla gene expression test results and melanoma hotspot driver mutations in 103 pigmented skin lesions clinically suspicious of melanoma. should be treated as melanoma in situ.3,11-13 correlation between increased mutational burden of pigmented lesions and more aggressive histologic stage has been reported.1,10 tert promoter mutations are furthermore independently associated with poor overall survival and more aggressive disease.2,10,14 the pla utilizes gene expression to objectively identify higher risk lesions; tert mutation analyses further expand actionable information. we show that tert mutations are present in 70% of pla positive melanomas, but in only 4% of sdn and non-melanoma lesions excluding sdn. the pla test enhanced by tert mutation analyses identifies molecular changes in pigmented lesions and provides additional data to assess disease risk beyond what can be ascertained visually. the improved ability to stratify risk non-invasively can guide decisions about which lesions require aggressive versus conservative management, ultimately sparing patients unnecessary biopsies and excisions. further, while biopsied dysplastic nevi can only be followed by monitoring for and judging the degree of atypia in re-pigmented scars, the non-invasive pla leaves a lesion intact and permits use of more validated skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 128 figure 1. pla gene expression and tert mutations in pigmented skin lesions clinically suspicious of melanoma. detectable levels of linc, prame or both target genes were found in 61% of sdn and in 93% of histopathologically melanomas. melanomas harbored tert promoter mutations in 70% of pla positive cases while sdn and non-melanomas without sdn harbored tert mutations in 4% of cases. linc (l), prame (p), detected (+), not detected (-). criteria of short-term monitoring. real-world pla use on now over 50,000 cases provides non-invasively obtained data sets that leave lesions intact for further monitoring and assessment of changes they may undergo. a recent large us registry study of 3,418 cases confirmed that clinicians follow the guidance of the pla (biopsying pla positive lesions while clinically monitoring pla negative ones) in over 98%, while reducing avoidable surgical biopsies of lesions clinically suspicious for melanoma by over 90%.15 findings presented here may further enhance clinician confidence in pla use by further stratifying risk in pigmented lesions. tert mutation analyses additionally help differentiate sdn from early melanomas and further increase pla performance. limitations of this study include the relatively small sample size and use of archival material. the generalizability of our findings is limited by the fact that in clinical practice most lesions are evaluated by a single pathologist or dermatopathologist with significant variability in diagnosing borderline lesions.3 pla positivity increases with histologic atypia of pigmented skin lesions. combining conclusion skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 129 tert mutation analyses with melanomaassociated gene expression provides additional genetic information to further noninvasively risk-stratify pigmented lesions. these findings furthermore support that pigmented lesions exist on a spectrum of genomic atypia that may prove useful in identifying borderline lesions beyond their morphological appearance. conflict of interest disclosures: srjc has done consulting for dermtech, lkf is an investigator for and an advisor of dermtech, bj and zy are employees of dermtech funding: this study was partially supported by dermtech corresponding author: laura k. ferris university of pittsburgh medical center (upmc) department of dermatology falk medical building, suite 5a 3601 fifth avenue pittsburgh, pa 15213 phone: 412-647-4200 email: ferrlk@upmc.edu references: 1. shain ah, yeh i, kovalyshyn i et al. the genetic evolution of melanoma from precursor lesions. n engl j med 2015; 373(20):1926-1936. 2. ferris lk, gerami p, skelsey mk et al. realworld performance and utility of a noninvasive gene expression assay to evaluate melanoma risk in pigmented lesions. melanoma res 2018; 28(5):478-482. 3. elmore jg, barnhill rl, elder de et al. pathologists' diagnosis of invasive melanoma and melanocytic proliferations: observer accuracy and reproducibility study. bmj 2017; 357:j2813. 4. kim cc, swetter sm, curiel-lewandrowski c et al. addressing the knowledge gap in clinical recommendations for management and complete excision of clinically atypical nevi/dysplastic nevi: pigmented lesion subcommittee consensus statement. jama dermatol 2015; 151(2):212218. 5. duffy k, grossman d. the dysplastic nevus: from historical perspective to management in the modern era: part i. historical, histologic, and clinical aspects. j am acad dermatol 2012; 67(1):1 e1-16; quiz 17-18. 6. engeln k, peters k, ho j et al. dysplastic nevi with severe atypia: long-term outcomes in patients with and without re-excision. j am acad dermatol 2017; 76(2):244-249. 7. gerami p, yao z, polsky d et al. development and validation of a noninvasive 2-gene molecular assay for cutaneous melanoma. j am acad dermatol 2017; 76(1):114-120 e112. 8. ferris lk, jansen b, ho j et al. utility of a noninvasive 2-gene molecular assay for cutaneous melanoma and effect on the decision to biopsy. jama dermatol 2017; 153(7):675-680. 9. haqq c, nosrati m, sudilovsky d et al. the gene expression signatures of melanoma progression. proc natl acad sci u s a 2005; 102(17):60926097. 10. ferris lk, moy rl, gerami p et al. noninvasive analysis of high-risk driver mutations and gene expression profiles in primary cutaneous melanoma. j invest dermatol 2019; 139(5):11271134. 11. duncan lm, berwick m, bruijn ja et al. histopathologic recognition and grading of dysplastic melanocytic nevi: an interobserver agreement study. j invest dermatol 1993; 100(3):318s-321s. 12. diagnosis and treatment of early melanoma. nih consensus development conference. january 27-29, 1992. consens statement 1992; 10(1):125. 13. culpepper ks, granter sr, mckee ph. my approach to atypical melanocytic lesions. j clin pathol 2004; 57(11):1121-1131. 14. nagore e, heidenreich b, requena c et al. tert promoter mutations associate with fastgrowing melanoma. pigment cell melanoma res 2016; 29(2):236-238. 15. brouha b, ferris lk, skelsey mk et al. realworld utility of a non-invasive gene expression test to rule out primary cutaneous melanoma: a large us registry study. jdd 2020; 19(3); doi:10.36849/jdd.2020.4766. skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 60 brief articles a case of alk-negative anaplastic large cell lymphoma presenting as a solitary cutaneous nodule venkat sumanth potluri, bs1, ronnie m. youssef, bs2, raymond m. fertig, md3, parneet k. dhaliwal, do4 1college of osteopathic medicine, nova southeastern university, davie, florida, usa 2college of medicine, texas a&m health science center, dallas, texas, usa 3department of dermatology, baylor scott and white, dallas, texas, usa 4department of pathology, baylor scott and white, dallas, texas, usa anaplastic large cell lymphoma (alcl) represents a group of cd30 positive t-cell non-hodgkin lymphomas unified by common morphologic and immunophenotypic characteristics, but with a spectrum of clinical presentations and behaviors.1 recognition of anaplastic lymphoma kinase (alk) gene rearrangements in some alcls led to alk being considered an important diagnostic and prognostic biomarker, and a key driver of alcl pathobiology. as per the 2017 world health organization updated classification, there are four distinct variants of alcl: alk-positive alcl (alk(+) alcl), alk-negative alcl (alk(-) alcl), primary cutaneous alcl (pc-alcl), and breastimplant associated alcl.1,2 the different subtypes of alcl share overlapping clinical presentations and pathologic features which can be diagnostically challenging.1 despite only accounting for 3-5% of all non-hodgkin lymphomas, distinguishing between each alcl subtype is important as treatment and prognoses vary.2,3 alk (-) alcl mimics alk (+) alcl morphologically and abstract anaplastic large cell lymphomas (alcls) are a group of cd30 positive t-cell non-hodgkin lymphomas, accounting for only 3% of all non-hodgkin lymphomas. as per the 2017 world health organization updated classification, there are four variants of alcl: anaplastic lymphoma kinase (alk) positive, alk negative, primary cutaneous, and breast-implant associated. the different variants of alcl share overlapping clinical presentations and pathologic features, creating a diagnostic challenge. a 71-year-old woman with a past history of t-cell lymphoma presented with a progressively growing nodule on her back for approximately 3 months. physical exam demonstrated a 8.0 x 8.0 cm pink nodular indurated plaque located on her left upper back. a punch biopsy of the lesion revealed medium to large mononuclear cells with nuclear pleomorphism, hyperchromasia, and scattered mitotic figures. immunohistochemistry demonstrated cells that were positive for cd30 and negative for alk. based on clinical and histopathologic findings, a diagnosis of alcl was rendered. differential diagnosis included primary cutaneous alcl and cutaneous involvement by systemic alk(-) alcl. this case demonstrates the importance of clinicopathologic correlation in diagnosing alcl and guiding therapy. introduction skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 61 immunohistochemically without the alk gene rearrangement, making these two entities readily distinguishable. however, alk(-) alcl and pc-alcl both lack the alk gene and are more difficult to discern since there are no robust pathognomonic features to identify them.1 alk (-) alcl and pc-alcl are known to be predominant in men and typically affect patients in late adulthood with alk(-) alcl having a median age of presentation of 65 years versus 55 years for pc-alcl.1 patients with alk(-) alcl usually present with “b” symptoms (fevers, night sweats, weight loss) whereas those with pc-alcl primarily present with cutaneous nodules; however, systemic alk(-) alcl has been known to have extranodal involvement in the skin in 20% of cases.1,2,4 herein, we describe the case of a patient who presented with an indurated nodular plaque which, upon biopsy and immunohistochemistry, was diagnostic of alcl with differential diagnoses including cutaneous involvement by systemic alk (-) alcl and pc-alcl. a 71-year-old woman with a remote history of t-cell lymphoma presented with a progressively growing nodule on her back for approximately 3 months. physical exam demonstrated a 8.0 x 8.0 cm pink nodular indurated plaque located on her left upper back (figure 1a). a punch biopsy of the lesion revealed an interstitial infiltrate within the reticular dermis (figure 1b) composed of medium to large mononuclear cells with nuclear pleomorphism, hyperchromasia, and scattered mitotic figures (figure 1c). the cells were shown infiltrating between collagen bundles with some having a more angiocentric distribution. no significant figure 1. (a) pink nodular indurated plaque located on the left upper back. (b) interstitial infiltrate within the reticular dermis. (c) medium to large mononuclear cells with nuclear pleomorphism, hyperchromasia, and scattered mitotic figures. case presentation skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 62 figure 2. immunohistochemistry demonstrating cells diffusely positive for cd45, cd4, and cd30 with areas of golgi pattern staining. epidermotropism was evident. immunohistochemistry demonstrated cells that were diffusely positive for cd4, cd45, and cd30 with areas of golgi pattern staining (figure 2). the tumor cells were negative for cd2, cd3, cd5, cd7, cd8, cd20, cd34, cd56, cd123, tia, granzyme, myeloperoxidase, hhv8, eber, and alk. a pet ct scan was performed which showed the lesion on the left upper back, but also a right breast mass and a thyroid nodule. a biopsy of the breast mass revealed an invasive ductal carcinoma. a thyroid biopsy was benign. given the localized lesion without extracutaneous involvement, a diagnosis of pc-alcl was rendered and the patient was scheduled for radiation therapy. after completion of radiation therapy, the patient exhibited complete resolution of the mass to her upper back without evidence of lymphadenopathy or recurrent disease. in order to distinguish between alk(-) alcl and pc-alcl, correlation with clinical and radiologic data is necessary. our patient presented with a solitary cutaneous nodule which is primarily characteristic of pc-alcl. alk(-) alcl and pc-alcl are almost identical morphologically and immunohistologically with both strongly positive for cd30 and negative for alk.1,5 both alk (-) alcl and pc-alcl have large cells with polylobulated nuclei. alk (-) alcl has the characteristic pathological feature of ‘hallmark’ cells, which resemble large cells with eccentric, kidney-shaped nuclei with a perinuclear eosinophilic golgi region. [1]. radiological imaging can assist in determining extracutaneous involvement and distinguishing between pc-alcl and cutaneous involvement of systemic alk(-) discussion skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 63 alcl since pc-alcl rarely disseminates beyond the skin.1,4 for our patient, a pet ct scan was critical in ruling out a cutaneous manifestation of systemic alk(-) alcl, especially given her remote history of t-cell lymphoma. ideally, genetic analysis can be ordered along with a pet scan to aid the diagnostic process. differentiating between alk(-) alcl and pc-alcl is important in determining an appropriate treatment regimen. observational studies and randomized control trials showing an effective treatment for alk(-) alcl are lacking; however, a treatment regimen of cyclophosphamide, doxorubicin, vincristine, and prednisone (chop) is frequently used as first-line therapy.2 patients with alk(-) alcl have relapsed after chop therapy, and recent studies have shown treatment with brentuximab vedotin to lead to a loss of cd30 expression.6,7 treatment for pc-alcl is dependent on whether it is a localized lesion or multifocal disease. for localized lesions, radiation therapy or surgical excision are the preferred methods of treatment.8 for multifocal or extracutaneous disease, short term chop therapy is often recommended.9 recurrence of disease after treatment with chop regimen has been seen in both alk(-) alcl and pc-alcl. further treatment is then recommended based on radiologic and clinical correlation. outcomes and survival rates for both alk(-) alcl and pc-alcl vary based on prescribed treatment and spread of disease. the 5-year overall survival for alk(-) alcl ranges from 17% to 90%, with the mean survival being 49%.10 studies have shown chop regimen to treat systemic alcl to complete remission rates of 56%.6 overall prognosis for patients diagnosed with pcalcl, both localized and multifocal, and treated with either surgical excision or radiation therapy is very favorable, with long term survival rates above 90%.11 our unique case does not serve as a guideline, but rather highlights the importance and inherent challenge of accurately diagnosing between the alcl variants. while the different subtypes share overlapping clinical and pathological features, the recommended treatment regimens and prognoses are distinct. as alcls are a rare group of non-hodgkin's lymphoma, large-scale clinical trials and literature remain scarce. further research focused on identifying clear immunohistochemical markers to differentiate alk(-) alcl and pc-alcl would assist physicians with diagnosis. conflict of interest disclosures: none funding: none corresponding author: parneet k. dhaliwal baylor university medical center 12557 granite falls trail frisco, texas 75035 phone: 469-834-9443 email: parneet.dhaliwal89@gmail.com references: 1. irshaid l, xu ml. alcl by any other name: the many facets of anaplastic large cell lymphoma. pathology. 2020;52(1):100-110. doi:10.1016/j.pathol.2019.09.007 2. kao ey, mukkamalla skr, lynch dt. cancer, alk negative anaplastic large cell lymphoma. in: statpearls. statpearls publishing; 2020. accessed june 20, 2020. http://www.ncbi.nlm.nih.gov/books/nbk519019/ 3. chihara d, fanale ma. management of anaplastic large cell lymphoma. hematology/oncology clinics of north america. 2017;31(2):209-222. doi:10.1016/j.hoc.2016.11.001 4. sridevi h, shanthala p, raghuveer c, et al. a rare case of alk negative cd30+ primary cutaneous anaplastic large cell lymphoma in a young adult. j can res ther. 2015;11(3):656. doi:10.4103/0973-1482.139338 https://doi.org/10.1016/j.pathol.2019.09.007 http://www.ncbi.nlm.nih.gov/books/nbk519019/ https://doi.org/10.1016/j.hoc.2016.11.001 https://doi.org/10.4103/0973-1482.139338 skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 64 5. moodley n, nombona p, mosam a. primary cutaneous anaplastic large-cell lymphoma. dermatopathology. 2019;6(2):163-169. doi:10.1159/000500259 6. ferreri aj, govi s, pileri sa, savage kj. anaplastic large cell lymphoma, alk-negative. crit. rev. oncol. hematol. 2013 feb;85(2):20615. 7. al-rohil rn, torres-cabala ca, patel a, tetzlaff mt, ivan d, nagarajan p, curry jl, miranda rn, duvic m, prieto vg, aung pp. loss of cd30 expression after treatment with brentuximab vedotin in a patient with anaplastic large cell lymphoma: a novel finding. j. cutan. pathol. 2016 dec;43(12):1161-1166. 8. piccinno r, damiani g, rossi lc, berti e. radiotherapy of primary cutaneous anaplastic large cell lymphoma: our experience in 30 cases. int j dermatol. 2020;59(4):469-473. doi:10.1111/ijd.14754 9. chao-lo mp, king-ismael d, lopez ra. primary cutaneous cd30+ anaplastic large cell lymphoma: report of a rare case. j dermatol case rep. 2008;2(3):31-34. doi:10.3315/jdcr.2008.1013 10. parrilla castellar er, jaffe es, said jw, et al. alk-negative anaplastic large cell lymphoma is a genetically heterogeneous disease with widely disparate clinical outcomes. blood. 2014;124(9):1473-1480. doi:10.1182/blood-201404-571091 11. bekkenk mw, geelen fa, van voorst vader pc, et al. primary and secondary cutaneous cd30(+) lymphoproliferative disorders: a report from the dutch cutaneous lymphoma group on the longterm follow-up data of 219 patients and guidelines for diagnosis and treatment. blood. 2000;95(12):3653-3661. https://doi.org/10.1159/000500259 acknowledgements: medical writing support was provided by prescott medical communications group (chicago, il) with financial support from ortho dermatologics; ortho dermatologics is a division of bausch health us, llc | presented at winter clinical dermatology conference 2020 • january 17-22, 2020 • kohala coast, hi synopsis ◾ psoriasis is a chronic, immune-mediated disease that varies widely in its clinical expression1 ◾ although plaque psoriasis can occur across different body regions, the lower extremities are one of the most commonly affected areas2 ◾ topical corticosteroids are the mainstay of psoriasis treatment; however, safety concerns limit their use3 ◾ recent phase 3 clinical data demonstrated the efficacy and tolerability of a fixed combination lotion containing halobetasol propionate 0.01% and tazarotene 0.045% (hp/taz; duobrii® ortho dermatologics, bridgewater, nj) in patients with moderate-to-severe localized plaque psoriasis4,5 objective ◾ to evaluate the efficacy and safety of hp/taz lotion in participants where the leg was identified as the target lesion methods ◾ in two phase 3, multicenter, randomized, double-blind studies (nct02462070; nct02462122), participants with moderate-to-severe plaque psoriasis were randomized (2:1) to receive hp/taz lotion or vehicle lotion once-daily for 8 weeks, with a 4-week posttreatment follow-up4,5 • at baseline, participants were required to have an investigator global assessment (iga) score of moderate (3) or severe (4) and body surface area (bsa) of 3% to 12% • in these studies, cerave® hydrating cleanser and cerave® moisturizing lotion (l’oreal, ny) were provided as needed for optimal moisturization/cleaning of the skin ◾ a pooled, post hoc analysis was conducted in a subset of participants with plaque psoriasis of the lower extremities, with a target lesion of the leg • for the target lesion, participants needed a score of ≥3 for at least 2 of 3 signs of psoriasis (erythema, plaque elevation, scaling: each on a 5-point scale; 0=clear and 4=severe), a sum of at least 8, and could not have a score 0 or 1 in any one of the signs • target could not be on areas covering bony prominences (i.e., knees); however, overall psoriasis assessment (iga and bsa) did not exclude the knees ◾ efficacy assessments included: treatment success (≥2-grade improvement from baseline) in each individual sign of psoriasis (erythema, plaque elevation, and scaling) at the target lesion (leg); overall treatment success (≥2-grade improvement from baseline in iga score and a score of ‘clear’ or ‘almost clear’ [0 or 1]); improvements in overall mean bsa from baseline; and mean change from baseline in igaxbsa composite score ◾ safety and treatment-emergent adverse events (teaes) were evaluated throughout the study results participants ◾ this analysis included 219 participants where the leg was identified as the target lesion (hp/taz lotion, n=148; vehicle, n=71) efficacy ◾ at the end of the 8-week treatment period, significantly more hp/taz-treated participants achieved ≥2-grade reduction in erythema, plaque elevation, and scaling compared with vehicle-treated participants; significant differences between hp/taz and vehicle were observed as early as week 2 and sustained posttreatment (figure 1) efficacy and safety of halobetasol propionate 0.01%/tazarotene 0.045% (hp/taz) lotion in the treatment of moderate to severe plaque psoriasis of the lower extremities figure 2. overall treatment successa by study visit in participants with a target lesion on the leg (itt population, pooled) 50% 60% 70% 40% 30% 20% 10% 0% 0 2 4 6 8 12 p e rc e n ta g e o f p a rt ic ip a n ts treatment posttreatment 7.7% 22.5% 33.5% 35.3% 10.9% 1.4% 5.7% 8.9% 10.4% 36.4% study visit (weeks) hp/taz lotion (n=148) vehicle (n=71) ** p<0.01 vs vehicle; *** p<0.001 vs vehicle. atreatment success is defined as a ≥2-grade improvement from baseline in iga score and a score of ‘clear’ or ‘almost clear’ (0 or 1). hp/taz, halobetasol propionate 0.01% and tazarotene 0.045%; iga, investigator global assessment; itt, intent-to-treat. figure 3. mean percent reduction in overall affected body surface area (bsa) by study visit in participants with a target lesion on the leg (itt population, pooled) -10% 0% 10% -20% -30% -40% 0 2 4 6 8 12 p e rc e n t c h a n g e f ro m b a se li n e treatment posttreatment -5.6% -18.7% -25.9% -34.8% 7.3% 3.1% 3.2% -0.9% -1.0% -32.7% study visit (weeks) hp/taz lotion (n=148) vehicle (n=71) * p<0.05 vs vehicle; *** p<0.001 vs vehicle. hp/taz, halobetasol propionate 0.01% and tazarotene 0.045%; itt, intent-to-treat. figure 4. mean percent reduction in igaxbsa composite by study visit in participants with a target lesion on the leg (itt population, pooled) -10% 0% 10% -20% -30% -50% -40% -60% 0 2 4 6 8 12 p e rc e n t c h a n g e f ro m b a se li n e treatment posttreatment -24.1% -35.7% -43.5% -47.2% -8.5% -3.0% -2.6% -4.8% -4.5% -47.3% study visit (weeks) hp/taz lotion (n=148) vehicle (n=71) *** p<0.001 vs vehicle. bsa, body surface area; hp/taz, halobetasol propionate 0.01% and tazarotene 0.045%; iga, investigator global assessment; itt, intent-to-treat. safety ◾ the most frequently reported treatment-related teaes were contact dermatitis, skin atrophy, folliculitis, and excoriation; 11 participants treated with hp/taz lotion discontinued due to teaes (table 1) table 1. treatment-emergent adverse events through week 8 in participants with a target lesion on the leg (safety population, pooled) participants, n (%) hp/taz lotion (n=144) vehicle (n=70) reporting any teaes 52 (36.1) 16 (22.9) reporting any saes 3 (2.1) 0 discontinued due to teaes 11 (7.6) 4 (5.7) severity of teaes reported mild 10 (6.9) 3 (4.3) moderate 29 (20.1) 9 (12.9) severe 13 (9.0) 4 (5.7) relationship to study drug related 34 (23.6) 7 (10.0) unrelated 18 (12.5) 9 (12.9) treatment-related teaes reported in ≥2% of participants contact dermatitis 11 (9.0) 0 skin atrophy 4 (2.8) 0 folliculitis 4 (2.8) 0 excoriation 3 (2.1) 0 pruritis 2 (1.4) 2 (2.9) skin burning sensation 2 (1.4) 2 (2.9) burning sensation (nervous system disorders) 2 (1.4) 2 (2.9) ae, adverse event; hp/taz, halobetasol propionate 0.01% and tazarotene 0.045%; sae, serious adverse event; teae, treatmentemergent adverse event. conclusions ◾ hp/taz lotion was associated with significant, rapid, and sustained reductions in disease severity in patients with moderate-to-severe psoriasis where the leg was identified as the target lesion, with good tolerability and safety over 8 weeks of once-daily use references 1. nestle fo, et al. n engl j med. 2009;361(5):496-509. 2. augustin m, et al. br j dermatol. 2019;181(2):358-365. 3. lam lh, et al. j drugs dermatol. 2016;15(8):945-948. 4. stein gold l, et al. j am acad dermatol. 2018;79(2):287-293. 5. sugarman jl, et al. j drugs dermatol. 2018;17(8):855-861. author disclosures stephen k. tyring is has acted as an investigator for ortho dermatologics. leon h. kircik has acted as an investigator, advisor, speaker, and consultant for ortho dermatologics. paul s. yamauchi has served as speaker, consultant, and investigator for abbvie, amgen, janssen, novartis, lilly, leo, ortho dermatologics, and sun pharma. naveen anbalagan and tina lin are employees of ortho dermatologics and may hold stock and/or stock options in its parent company. figure 1. treatment successa in psoriasis signs of erythema (a), plaque elevation (b), and scaling (c) at the leg target lesion by study visit (itt population, pooled) 50% 60% 70% 40% 30% 20% 10% 0% 0 2 4 6 8 12 50% 60% 70% 40% 30% 20% 10% 0% 0 2 4 6 8 12 50% 60% 70% 40% 30% 20% 10% 0% 0 2 4 6 8 12 12 12 12 p e rc e n ta g e o f p a rt ic ip a n ts a. erythema treatment posttreatment 14.1% 28.4% 36.2% 44.6% 17.3% 1.5% 7.2% 9.4% 12.5% 41.6% p e rc e n ta g e o f p a rt ic ip a n ts b. plaque elevation treatment posttreatment 27.8% 44.0% 52.3% 53.2% 27.9% 11.3% 10.1% 17.8% 19.2% 58.5% p e rc e n ta g e o f p a rt ic ip a n ts c. scaling treatment posttreatment 31.1% 48.7% 54.1% 54.4% 26.0% 5.7% 10.4% 17.6% 21.0% 59.5% study visit (weeks) hp/taz lotion (n=148) vehicle (n=71) study visit (weeks) hp/taz lotion (n=148) vehicle (n=71) study visit (weeks) hp/taz lotion (n=148) vehicle (n=71) ** p<0.01 vs vehicle; *** p<0.001 vs vehicle. atreatment success is defined as a ≥2-grade improvement from baseline in each individual sign of psoriasis at the target lesion. hp/taz, halobetasol propionate 0.01% and tazarotene 0.045%; itt, intent-to-treat. ◾ significantly more participants achieved overall treatment success (per iga scores) at week 8 with hp/taz compared with vehicle (figure 2) ◾ the hp/taz group also had a significantly greater mean percent reduction in bsa at week 8 versus vehicle (figure 3) ◾ change from baseline in igaxbsa composite score was significantly improved with hp/taz lotion versus vehicle at all study visits assessed (figure 4) stephen k tyring, md, phd1; leon h kircik, md2; paul s yamauchi, md, phd3; naveen anbalagan, md4; tina lin, pharmd4 1university of texas health science center, houston, tx; 2indiana university school of medicine, indianapolis, in; physicians skin care, pllc, louisville, ky; and icahn school of medicine at mount sinai, new york, ny; 3dermatology institute & skin care center, inc., santa monica, ca; 4ortho dermatologics*, bridgewater, nj *ortho dermatologics is a division of bausch health us, llc. powerpoint presentation david m. pariser1, lawrence j. green2, edward l. lain3, carsten schmitz4*, amy s. chinigo4, brian mcnamee5, david r. berk4*, jamison hoffman6, ayman grada6 1eastern virginia medical school and virginia clinical research, inc., norfolk, va, usa; 2george washington university school of medicine, washington, dc, usa; 3austin institute for clinical research, pflugerville, tx, usa; 4allergan plc, irvine, ca, usa; 5allergan biologics ltd, liverpool, uk; *former employees; 6almirall llc., exton, pa, usa email: ayman.grada@almirall.com table 4. overall summary of patients with adverse events (safety population) • sarecycline is a novel, narrow-spectrum, once-daily, oral tetracycline-class antibiotic indicated for the treatment of inflammatory lesions of non-nodular moderate-to-severe acne1 • poor tolerability and bacterial resistance concerns may limit the use of broad-spectrum tetracycline antibiotics for the treatment of acne1 background • to evaluate the long-term safety, tolerability, and patterns of use for the once-daily oral, narrow-spectrum antibiotic sarecycline in patients with moderate-to-severe acne vulgaris during a 40-week phase iii, multicenter, open-label extension study1 • additionally, a phase i, single-center, randomized, double-blind, placebo-controlled, crossover study conducted to evaluate the potential of sarecycline to cause phototoxicity1 objective open-label safety evaluation • patients aged 9-years of age or older with moderate-to-severe acne who completed one of two prior phase iii, double-blind, placebocontrolled, 12-week trials in which they received sarecycline 1.5mg/kg/ day or placebo were included 1,2 • primary assessment was the safety of sarecycline treatment over one year as measured by adverse events (aes), vital signs, electrocardiograms (ecgs), clinical laboratory tests, and physical examinations • study visits occurred at weeks 2, 6, 12, 18, 24, 32, and 40 phototoxicity study • 19 subjects (healthy; non-smoker, men, aged 18 to 45 years) received placebo or 240mg of sarecycline in a random order in each of the two treatment periods (not weight based) • a two-treatment, two-period, two-sequence crossover design. treatment periods were separated by at least nine days • at three hours after administration of the study treatment, a previously unexposed area of each subject’s back was irradiated with 16j/cm2 of uva, after which point, another area was irradiated with uva/uvb at 50 percent of the subject’s minimum erythemal dose (med) • uv-exposed skin was assessed visually at 24, 48, and 72 hours after irradiation, and uv-induced skin reaction was evaluated using dermal response score scale • mean and maximum numerical uv-induced dermal response scores were determined for sarecycline and placebo methods financial support: this study was funded and sponsored by allergan. sarecycline is owned and marketed by almirall, llc. disclosures 1. pariser, david m., lawrence j. green, carsten schmitz, amy chinigo, brian mcnamee, and david r. berk. “safety and tolerability of sarecycline for the treatment of acne vulgaris: results from a phase iii, multicenter, open-label study and a phase i phototoxicity study : jcad: the journal of clinical and aesthetic dermatology.” jcad, november 1, 2019. http://jcadonline.com/sarecycline-acne/. clinicaltrials.gov registration: nct02413346 2. moore a, green lj, bruce s, sadick n, tschen e, w erschler p, cook-bolden fe, dhawan ss, forsha d, gold mh, guenthner s. once-daily oral sarecycline 1.5 mg/kg/day is effective for moderate to severe acne vulgaris: results from two identically designed, phase 3, randomized, double-blind clinical trials. journal of drugs in dermatology: jdd. 2018 sep;17(9):987-96. references • sarecycline was associated with low rates of teaes, with nasopharyngitis, upperrespiratory-tract infection, headache, and nausea being the only teaes reported by two percent or more of patients with moderate-to-severe acne vulgaris aged nine years or older treated with sarecycline once daily for up to 40 weeks. • adverse events commonly associated with other tetracycline antibiotics such as dizziness, sunburn, nausea, vomiting, and diarrhea were low • no clinically meaningful safety findings were noted conclusion • the safety population included 483 patients; 354 patients (73.3%) completed the study 1 • the most common teaes were nasopharyngitis (3.7%), upperrespiratory-tract infection (3.3%), headache (2.9%), and nausea (2.1%). clinical laboratory evaluations suggested no clinically meaningful differences between the treatment sequences 1 • rates of teaes commonly associated with other tetracycline antibiotics were for dizziness (0.4%) and sunburn (0.2%), and for gastrointestinal teaes, nausea (2.1%), vomiting (1.9%), and diarrhea (1.0%). vulvovaginal mycotic infection (0.8%) 1 • dermal response to uv exposure did not exceed mild erythema with either sarecycline or placebo at any time point, and the mean and maximum uv-induced dermal response scores for both sarecycline and placebo were low. no teaes or serious aes were reported in the phototoxicity study results table 1. summary of subject demographics and baseline characteristics1 placebo / sarecyclinea (n=236) sarecycline / sarecyclineb (n=247) totalc (n=483) mean (sd) age, years 18.7 (6.0) 18.4 (5.9) 18.5 (6.0) ≥9 and <12 years 2 3 5 ≥12 and <18 years 138 152 290 ≥18 years 96 92 188 gender, n (%) 48.3 49.4 48.9 female 122 (51.7) 125 (50.6) 247 (51.1) male 114 (48.3) 122 (49.4) 236 (48.9) bmi, mean (sd), kg/m2 25.07 (5.4) 25.36 (6.1) 25.22 (5.8) race, n (%) white 198 (83.9) 201 (81.4) 399 (82.6) black or african american 28 (11.9) 29 (11.7) 57 (11.8) other 10 (4.2) 16 (6.5) 26 (5.4) investigator’s global assessment, n (%) 3 (moderate) 191 (80.9) 207 (83.8) 398 (82.4) 4 (severe) 45 (19.1) 40 (16.2) 85 (17.6) athe placebo/sarecycline population contained patients who received placebo in the placebocontrolled, double-blind lead-in trials. b the sarecycline/sarecycline populations contained patients who received sarecycline in the placebo-controlled, double-blind lead-in trials. c safety population included all participants among the screened population who were exposed to study treatment (sarecycline) in either the double-blind lead-in study or this open-label extension study. sd, standard deviation table 3. common teaes (≥2% of patients in either group; safety population) patients, n (%) placebo / sarecyclinea (n=236) sarecycline / sarecyclineb (n=247) totalc (n=483) nasopharyngitis 13 (5.5) 5 (2.0) 18 (3.7) upper-respiratorytract infection 7 (3.0) 9 (3.6) 16 (3.3) headache 9 (3.8) 5 (2.0)b 14 (2.9)b nausea 4 (1.7)b 6 (2.4) 10 (2.1)b vomiting 3 (1.3)b 6 (2.4) 9 (1.9)b urinary tract infection 2 (0.8) 5 (2.0) 7 (1.4) aone patient in each treatment group had an ae that occurred more than 30 days after the dose of sarecycline. bone of these teaes was an ae that occurred more than 30 days after the last dose of sarecycline but before study completion. ae: adverse event; teae: treatment-emergent adverse event. study sc 1402 sarecycline 1.5 mg/kg/day placebo once daily study sc 1403 sarecycline 1.5 mg/kg/day as required table 2. summary of subject demographics and baseline characteristics 1 (phase-l phototoxicity study) total (n = 19) age, mean (sd), years 30.7 (9.0) white, n (%) 19 (100) hispanic/latino, n (%) 6 (31.6) body mass index, mean (sd), kg/m2 26.1 (2.5) fitzpatrick skin phototype, n (%) i 3 (15.8) ii 7 (36.8) iii 9 (47.4) sd: standard deviation. anumber enrolled and randomized; one subject was lost to follow -up and excluded from phototoxicity analysis. paitents, n (%) placebo / sarecyclinea (n=236) sarecycline / sarecyclineb (n=247) totalc (n=483) any teae 94 (39.8) 94 (38.1) 188 (38.9) any severe teae 3 (1.3) 2 (0.8) 5 (1.0) saes 2 (0.8) 2 (0.8) 4 (0.8) abdominal pain 0 1 (0.4) 1 (0.2) anemia 1 (0.4) 0 1 (0.2) dehydration 0 1 (0.4) 1 (0.2) headachea 1 (0.4) 0 1 (0.2) peptic ulcerb 1 (0.4) 0 1 (0.2) aconsidered possibly related to study treatment according to the investigator’s assessment bexperienced by the same patient with anemia sae: serious adverse event; teae: treatment-emergent adverse event safety and tolerability of sarecycline for the treatment of acne vulgaris results from a phase ill, multicenter, open-label extension study and a phase i phototoxicity study study sc 1401 sarecycline 1.5 mg/kg/day placebo once daily http://jcadonline.com/sarecycline-acne/ skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 148 brief articles the successful treatment of multiple cutaneous malignancies with hpv vaccination: case report solomon geizhals ba1, mark g lebwohl md2 1suny downstate medical school, brooklyn, ny 2department of dermatology, icahn school of medicine at mount sinai, new york, ny an immunocompetent 84-year-old woman presented to a university-based outpatient dermatology clinic with more than 20 domeshaped crusted nodules that were superimposed on a large, sharply demarcated erythematous plaque of psoriasis on her right leg (figure 1a). histopathologic examination of one of the nodules revealed an invasive squamous cell carcinoma (scc) of the keratoacanthoma variant. considering the patient’s advanced age, location of the tumors and extensive tumor burden, invasive therapy was deemed unfeasible and a different therapeutic approach was warranted. initially, oral acitretin 25 mg/day was prescribed to treat both the psoriasis1 and the multiple keratoacanthomas.2 after 3 months of treatment, the tumors had all clinically resolved and the underlying psoriatic plaque nearly gone. however, due to complaints of increased skin-dryness, cheilitis, and some mild hair loss, the acitretin dosage was decreased to 10 mg/every other day with concurrent betamethasone dipropionate 0.05% ointment twice daily for 4 weeks and then twice per week after that. unfortunately, 5 months later, there was a recurrence of multiple histopathologicallyconfirmed keratoacanthomas. after the patient declined increasing the acitretin dosage or any systemic therapy, she was treated off-label with vaccine administration. she was treated twice intramuscularly and three times intralesionally with the 9-valent hpv vaccine (0.5 ml each time) from september 12, 2018 through july 22, 2019. clinical improvement was observed after two injections of the 9-valent hpv vaccine case report an elderly, immunocompetent patient presented multiple invasive squamous cell carcinomas of the keratoacanthoma subtype superimposed on a psoriatic plaque. after failing initial treatment with oral acitretin, alternative therapies were considered. due to the patient’s advanced age, location of the tumors and extensive tumor burden, invasive therapy was deemed impractical. after careful consideration, the more novel approach of injecting the 9valent hpv vaccine was performed. ten months after the first dose, the patient’s skin displayed neither clinical or histologic evidence of any residual cancer. we believe that this is the second reported case of the 9-valent hpv vaccine successfully treating non-melanoma cutaneous malignancies. abstract skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 149 with reduction in tumor size and number (figure 1b) after each injection. ten months after the first dose, there was no clinical or histologic evidence of residual scc. on examination, there were small violaceous discolored patches and scars on her right leg at sites corresponding to previous tumors (figure 1c). figure 1. clinical image of the right calf of an 84year-old woman. complete tumor regression was observed 10 months after the first dose of vaccine. a. prior to any injections b. three-months after 2 sets of injections. c. ten months after first injection. standard of care for non-melanoma skin cancers generally entails excision of the cutaneous malignancy, with limited alternatives. those with multiple lesions or poor surgical candidates are left with few options for appropriate therapy. however, recent evidence suggests that the human papillomavirus (hpv), specifically the β-hpv subtypes types 5, 8, 15, 17, 20, 24, 36, and 38, contributes to the pathogenesis of scc.3-4 current evidence suggests that these β-hpv types play a role at an early stage of skin carcinogenesis, but are not required for the viability and maintenance of the malignant cell after development of the skin tumor.5 regardless of the exact pathogenesis, the growing evidence showing the association between scc prevalence and hpv infection can potentially help create new therapeutic avenues in reducing cutaneous malignancy prevalence.6 the 9-valent hpv vaccine is approved by the us food and drug administration to prevent genital warts and anogenital cancer caused by hpv infection.7 it provides coverage only against the sexually transmitted α-hpvs, essential etiological variants in cervical, anal, penile, discussion skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 150 vaginal, vulvar, and some oropharyngeal cancers, but not against β-hpv types.6-7 although the β-hpv subtype has been viewed as the main culprit in cutaneous malignancy pathogenesis, nevertheless, some patients that received the more limited quadrivalent vaccine reduced new scc development in immunocompetent patients without known hpv infection.8 another recent study reported the complete regression of multiple cutaneous basaloid squamous cell carcinomas in a 90-year-old female following both intratumoral and intramuscular injections of the 9-valent hpv vaccine (gardasil-9; merck & co inc).9 the mechanism of action is unclear; either due to an activation of innate immunity in response to the aluminum adjuvant in the vaccine,10 or more likely, to the contributing viral component.11 most keratoacanthomas are self-resolving benign epidermal lesions, but are generally considered a well-differentiated variant of scc.2 moreover, it has been posited that a keratoacanthoma may represent a midpoint between a viral wart and invasive scc, hence its propensity for spontaneous regression.4 hence, since our patient continued to present with persistent keratoacanthomas after acitretin treatment and declined systemic therapy, this led to the consideration of the use of off-label treatments. the data supporting the use of intratumoral vaccine injections in eliciting immune responses capable of eradicating tumor cells12 coupled with the evidence showing a strong relationship between hpv and non-melanotic skin cancers led us to treat and now report a 2nd case in which a patient’s multiple cutaneous malignancies were successfully treated with the hpv vaccine. conflict of interest disclosures: none funding: none corresponding author: mark g lebwohl md 5 east 98th street, ny, ny 10029 phone: 212-241-9728 fax: 212-876-5661 email: mark.lebwohl@mountsinai.org references: 1. l. c. guenther, r. kunynetz, c. w. lynde et al. acitretin use in dermatology. j cutan med surg 2017; 21: 2s-12s. 2. j. a. savage, j. c. maize, sr. keratoacanthoma clinical behavior: a systematic review. am j dermatopathol 2014; 36: 422-429. 3. j. chahoud, a. semaan, y. chen et al. association between beta-genus human papillomavirus and cutaneous squamous cell carcinoma in immunocompetent individuals-a meta-analysis. jama dermatol 2016; 152: 13541364. 4. b. aldabagh, j. g. c. angeles, a. r. cardones, s. t. arron. cutaneous squamous cell carcinoma and human papillomavirus: is there an association? dermatologic surgery : official publication for american society for dermatologic surgery [et al.] 2013; 39: 1-23. 5. d. e. rollison, d. viarisio, r. p. amorrortu, t. gheit, m. tommasino. an emerging issue in oncogenic virology: the role of beta human papillomavirus types in the development of cutaneous squamous cell carcinoma. journal of virology 2019; 93: e01003-01018. 6. j. chahoud, a. g. rieber, s. k. tyring. the betahpv subtypes-cornerstone of the nextgeneration vaccine. jama oncol 2017; 3: 594595. 7. us food and drug and administration. gardasil 9. https://www.fda.gov/vaccines-bloodbiologics/vaccines/gardasil-9. accessed october 25, 2019. 8. a. j. nichols, a. h. allen, s. shareef, e. v. badiavas, r. s. kirsner, t. ioannides. association of human papillomavirus vaccine with the development of keratinocyte carcinomas. jama dermatol 2017; 153: 571574. 9. a. j. nichols, a. gonzalez, e. s. clark et al. combined systemic and intratumoral administration of human papillomavirus vaccine mailto:mark.lebwohl@mountsinai.org https://www.fda.gov/vaccines-blood-biologics/vaccines/gardasil-9 https://www.fda.gov/vaccines-blood-biologics/vaccines/gardasil-9 skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 151 to treat multiple cutaneous basaloid squamous cell carcinomas. jama dermatol 2018; 154: 927-930. 10. f. brunet-possenti, l. deschamps, c. charpentier. use of combination systemicintratumoral hpv vaccine to treat cutaneous basaloid squamous cell carcinomas. jama dermatol 2019; 155: 123-124. 11. a. j. nichols, r. s. kirsner, t. ioannides. use of combination systemic-intratumoral hpv vaccine to treat cutaneous basaloid squamous cell carcinomas—reply. jama dermatology 2019; 155: 124-125. 12. a. oglesby, a. p. algazi, a. i. daud. intratumoral and combination therapy in melanoma and other skin cancers. am j clin dermatol 2019. introduction • upper facial lines (ufl) can negatively influence self-perception and have adverse psychological impacts1-3 • subject satisfaction with aesthetic treatment reflects successful treatment outcomes, which in turn may be associated with improved self-esteem and body image1,2 • onabotulinumtoxina has been used effectively and safely to treat facial lines since the early 1990s4,5 • when treating forehead lines (fhl), concurrent treatment of glabellar lines (gl) is recommended to reduce risk of eyebrow ptosis by maintaining a balance between eyebrow elevator muscles (primarily the frontalis muscle) and depressor muscles (including the procerus and corrugator muscles making up the glabellar complex)6 • clinical studies further support the use of onabotulinumtoxina for treatment of ufl, with fhl treatment administered concurrently with treatment for gl and crow’s feet lines (cfl)7,8 • the safety and efficacy of onabotulinumtoxina for treating fhl and gl (40 u total) or fhl and gl with simultaneous treatment of cfl (64 u total) was evaluated in a 12-month phase 3 study9 ─ the primary endpoint was met (proportion of subjects achieving ≥2-grade improvement from baseline in investigator and subject facial wrinkle scale with photonumeric guide [fws] scores of fhl severity at maximum eyebrow elevation; 53.0% with onabotulinumtoxina 64 u and 45.6% with onabotulinumtoxina 40 u vs 0.6% with placebo on day 30; both p<0.0001) objective • to present results from a 12-month, phase 3 study on the effects of onabotulinumtoxina on patient-reported satisfaction and to assess impacts of treatment methods patients • neurotoxin-naive males and females aged ≥18 years with: ─ moderate to severe fhl at maximum eyebrow elevation (as assessed by both investigator and subject using the fws on study day 1 prior to treatment) ─ moderate to severe gl at maximum frown (as assessed by the investigator on the fws on study day 1) ─ moderate to severe bilaterally symmetrical cfl at maximum smile (as assessed by the investigator on the fws on study day 1) study design • this 12-month phase 3 study was conducted at 10 sites in the united states and 14 sites in europe from october 2014 to april 2016 • the study included a 6-month, double-blind, placebo-controlled, parallel-group treatment period (days 1–180) followed by a 6-month open-label treatment period (days 180–360) (figure 1) figure 1. study design w1 w2 d30 d60 d90 d120 d150 d180 d210 d240 d270 d300 d330 d360 screening and randomization (2.2:1) period 1–double-blind treatment period 2–open-label treatment 40 u (20 u fhl + 20 u gl + pbo cfl); n=300 64 u (20 u fhl + 20 u gl + 24 u cfl); n=750 study exit pbo (pbo fhl + pbo gl + pbo cfl); n=150 screening, randomization, and treatment follow-up visit follow-up/criteria-based treatment visit 64 u (20 u fhl + 20 u gl + 24 u cfl); n=300 cfl, crow’s feet lines; d, day; fhl, forehead lines; gl, glabellar lines; pbo, placebo; w, week. • eligible subjects were randomized (2:2:1) to receive one of the following treatments: ─ onabotulinumtoxina 64 u (20 u in fhl, 20 u in gl, and 24 u in cfl) ─ onabotulinumtoxina 40 u (20 u in fhl, 20 u in gl, and placebo in cfl) ─ placebo • onabotulinumtoxina 4 u or placebo was given as 0.1 ml at 16 injection sites (figure 2) • following the double-blind period, subjects entered the open-label treatment period, during which they could receive up to 2 onabotulinumtoxina 64 u treatments using the same 16-injection site paradigm, with at least 84 days separating treatment cycles • follow-up assessments were made at weeks 1 and 2 after each study treatment; all subjects also had follow-up visits every 30 days starting on study day 30 though day 360 figure 2. injection sites for treatment of forehead lines, glabellar lines, and crow’s feet lines forehead glabellar crow’s feet lines patient-reported outcome (pro) measures • subjects completed the facial line satisfaction questionnaire (flsq) and the 11-item facial line outcomes questionnaire (flo-11) at baseline, on days 7, 14, and 30, then every 30 days through day 360 • both pro instruments were developed, validated, and implemented in accordance with us food and drug administration guidance10,11 • flsq (11 questions at baseline and 13 questions at follow-up) is designed to assess treatment satisfaction and appearance-related impacts associated with facial lines in the fhl, gl, and/or cfl areas from the subject’s perspective ─ flsq item 5 assesses the subjects’ satisfaction with treatment of their facial lines ─ flsq impact domain measures appearance-related and emotional impacts of treatment, including appearance-related age, anger, tiredness, emotional unhappiness, and negative self-esteem • flo-11 assesses psychological and appearance-related impacts associated with facial lines in the forehead, glabellar, and crow’s feet areas, from the subjects’ perspective ─ flo-11 item 4 evaluates whether subjects feel that they look older than their actual age statistical analysis • flsq item 5, flsq impact domain, and flo-11 item 4 were included as key secondary efficacy endpoints as they reflect the subject’s perception of treatment effects and drive retreatment decisions ─ proportion of subjects mostly satisfied or very satisfied on flsq item 5 (primary time point: day 60) ─ proportion of responders on flsq impact domain, defined by a ≥20-point improvement from baseline (primary time point: day 30) ─ proportion of responders on flo-11 item 4, defined by a ≥3-point improvement from baseline (primary time point: day 30) for subjects with baseline scores ≤80 • these pro measures were evaluated in the intent-to-treat (itt) population, consisting of all randomized subjects • comparisons between the onabotulinumtoxina groups versus placebo were conducted using the cochran-mantel-haenszel test, stratified by study site, with statistical significance achieved at p≤0.05 results subjects • the itt population comprised 787 subjects, including 313 in the onabotulinumtoxina 64 u group, 318 in the onabotulinumtoxina 40 u group, and 156 in the placebo group ─ overall, 728 subjects (92.5%) received a second treatment cycle and 510 subjects (64.8%) received a third treatment cycle during the open-label period • the majority of subjects completed the study (n=684; 86.9%); discontinuations were mostly due to being lost to follow-up (n=49; 6.2%) or personal reasons (n=44; 5.6%) • demographics and baseline characteristics were similar among treatment groups (table 1) table 1. subject demographics and baseline characteristics (itt population) parameter onabotulinumtoxina 64 u (n=313) onabotulinumtoxina 40 u (n=318) placebo (n=156) age, mean, years 45.5 47.6 48.1 range 21–76 22–75 22–73 female, n (%) 284 (90.7) 278 (87.4) 140 (89.7) caucasian, n (%) 285 (91.1) 287 (90.3) 145 (92.9) fhl severity at maximum eyebrow elevation, subject fws rating, n (%) moderate 162 (51.8) 171 (53.8) 82 (52.6) severe 151 (48.2) 147 (46.2) 74 (47.4) gl severity at maximum frown, investigator fws rating, n (%)* moderate 119 (38.0) 101 (31.8) 49 (31.4) severe 194 (62.0) 217 (68.2) 106 (67.9) cfl severity at maximum smile, investigator fws rating, n (%) moderate 140 (45.0) 123 (38.8) 66 (42.9) severe 171 (55.0) 194 (61.2) 88 (57.1) flo-11 item 4 score,† mean (range) 6.4 (0–10) 6.2 (0–10) 6.1 (0–10) flsq impact domain score,‡ mean (range) 60.7 (5–100) 58.9 (0–100) 59.1 (15–100) *one subject in the placebo group had a rating of mild. †flo-11 item 4 was scored on a scale from 0 (“not at all”) to 10 (“very much”). ‡ flsq impact domain scored from 0 to 100, with higher scores indicating that facial lines had greater negative impact on the subject. cfl, crow’s feet lines; fhl, forehead lines; flo-11, 11-item facial lines outcome questionnaire; flsq, facial line satisfaction questionnaire; fws, facial wrinkle scale; gl, glabellar lines; itt, intent-to-treat. flsq item 5 • the proportion of subjects who were mostly or very satisfied with onabotulinumtoxina 64 u and 40 u was significantly greater than with placebo, respectively, on day 30 (89.8% and 82.0% vs 5.8%; both p<0.0001) and on day 60, the primary time point (87.9% and 81.4% vs 3.2%; both p<0.0001) • subject satisfaction with treatment remained significantly higher in both onabotulinumtoxina groups compared with placebo at all time points through the end of the double-blind treatment period (ie, day 180) (all, p<0.0001) (figure 3) • during the open-label period, subject satisfaction was maintained with repeated onabotulinumtoxina 64 u treatment, including in subjects initially allocated to placebo figure 3. subjects mostly satisfied or very satisfied on flsq item 5 during the entire 12-month study 0 10 20 30 40 50 60 70 80 90 100 day 7 day 14 day 30 day 60 day 90 day 120 day 150 day 180 day 7 day 14 day 30 day 60 day 90 day 7 day 14 day 30 day 60 day 90 m os tly s at is fie d or v er y s at is fie d (% ) visit day onabotulinumtoxina 64 u (n=313) onabotulinumtoxina 40 u (n=317, cycle 1) onabotulinumtoxina 64 u placebo (n=155, cycle 1) onabotulinumtoxina 64 u cycle 1: double-blind cycle 2: open-label cycle 3: open-label period 1 period 2 * * * * * * * * *p<0.0001 for both onabotulinumtoxina groups vs placebo. flsq impact domain • the responder rate on the flsq impact domain was significantly greater in the onabotulinumtoxina 64 u and 40 u groups versus placebo on day 30 (76.1% and 61.0% vs 19.7%; both p<0.0001) • the flsq impact domain responder rate remained significantly higher with onabotulinumtoxina 64 u (all p<0.0001) and 40 u (p≤0.0009) versus placebo at all time points through day 180 (figure 4) • during the open-label treatment period, flsq impact domain responder rates were generally maintained with repeated onabotulinumtoxina 64 u treatment (figure 4) figure 4. responders reporting ≥20-point improvement from baseline on flsq impact domain during the entire 12-month study (subjects with baseline score ≥20) 0 10 20 30 40 50 60 70 80 90 100 day 7 day 14 day 30 day 60 day 90 day 120 day 150 day 180 day 7 day 14 day 30 day 60 day 90 day 7 day 14 day 30 day 60 day 90 r es po nd er s on f ls q im pa ct d om ai n (% ) visit day onabotulinumtoxina 64 u (n=301) onabotulinumtoxina 40 u (n=310, cycle 1) onabotulinumtoxina 64 u placebo (n=152, cycle 1) onabotulinumtoxina 64 u cycle 1: double-blind cycle 2: open-label cycle 3: open-label * * * * * * * † period 1 period 2 *p<0.0001; †p≤0.0009 for both onabotulinumtoxina groups vs placebo. flo-11 item 4 • the responder rate on flo-11 item 4 (looking older than actual age) was significantly greater in the onabotulinumtoxina 64 u and 40 u groups versus placebo on day 30 (77.1 and 66.7% vs 9.9%; both p<0.0001) • the flo-11 item 4 responder rate remained significantly higher with onabotulinumtoxina 64 u and 40 u versus placebo at all time points through day 180 (p≤0.0001) (figure 5) • like the other pro measures, the flo-11 responder rate was generally maintained with repeated onabotulinumtoxina 64 u treatment during the open-label period (figure 5) figure 5. responders reporting ≥3-point improvement from baseline on flo-11 item 4 during the entire 12-month study (subjects with baseline score ≥3) 0 10 20 30 40 50 60 70 80 90 100 day 7 day 14 day 30 day 60 day 90 day 120 day 150 day 180 day 7 day 14 day 30 day 60 day 90 day 7 day 14 day 30 day 60 day 90 r es po nd er s on f lo -1 1 ite m 4 (% ) visit day onabotulinumtoxina 64 u (n=288) onabotulinumtoxina 40 u (n=285, cycle 1) onabotulinumtoxina 64 u placebo (n=141, cycle 1) onabotulinumtoxina 64 u cycle 1: double-blind cycle 2: open-label cycle 3: open-label * * * * * * * † period 1 period 2 *p<0.0001; †p≤0.0001 for both onabotulinumtoxina groups vs placebo. conclusions • subjects were highly satisfied with onabotulinumtoxina 64 u treatment of ufl (fhl, gl, and cfl) and with onabotulinumtoxina 40 u treatment of fhl and gl • with both onabotulinumtoxina regimens, subjects reported significant improvements in appearance-related and emotional impacts of their facial lines • the improvements in pros were sustained for at least 6 months after a single treatment cycle, and were maintained thereafter with repeated onabotulinumtoxina treatment references 1. finn cj, et al. dermatol surg. 2003;29(5):450-5. 2. cox se, finn jc. int ophthalmol clin. 2005;45(3):13-24. 3. gupta ma, gilchrest ba. dermatol clin. 2005;23(4):643-8. 4. carruthers jd, carruthers ja. j dermatol surg oncol. 1992;18(1):17-21. 5. carruthers j, et al. dermatol surg. 2015;41(6):702-11. 6. lorenc zp, et al. aesthet surg j. 2013;33(1 suppl):35s-40s. 7. carruthers j, carruthers a. dermatol surg. 2007;33(1 spec no.):s10-s7. 8. michaels bm, et al. aesthet surg j. 2012;32(1):96-102. 9. de boulle k, et al. presented at: international master course on aging sciences; february 1-3, 2017; paris, france. 10. pompilus f, et al. j cosmet dermatol. 2015;14(4):274-85. 11. yaworsky a, et al. j cosmet dermatol. 2014;13(4):297-306. acknowledgments this study was sponsored by allergan plc, dublin, ireland. medical writing and editorial assistance was provided to the authors by cactus communications and was funded by allergan plc. all authors met the icmje authorship criteria. neither honoraria nor other form of payments were made for authorship. financial disclosures s dayan has received research support or speaking/consultant fees from allergan plc, galderma, merz aesthetics, and valeant. p ogilvie serves as an investigator for allergan plc. az rivkin serves as a consultant and investigator for allergan plc and merz aesthetics. sg yoelin serves as a consultant and investigator for allergan plc. jk garcia is an employee of allergan plc and may own stock/options in the company. il ferrusi was an employee of allergan plc at the time of this study. presented at the fall clinical dermatology conference, las vegas, october 12-15, 2017 simultaneous treatment of moderate to severe horizontal frontalis lines, glabellar lines, and lateral canthal lines with onabotulinumtoxina from the subject’s perspective: patient-reported satisfaction and impact outcomes from a phase 3 double-blind study steven dayan, md1; patricia ogilvie, md, phd2; alexander z. rivkin, md3; steven g. yoelin, md4; julie k. garcia, phd5; ilia l. ferrusi, phd5 1denova research, chicago, il; 2skinconcept, munich, germany; 3david geffen school of medicine, ucla, los angeles, ca; 4medical associates inc., newport beach, ca; 5allergan plc, irvine, ca to obtain a pdf of this poster scan the qr code or visit www.allergancongressposters.com/968515 charges may apply. no personal information is stored. to view a video of the mechanism of action of botox, scan the qr code, then click on the “narrated poster” button. when prompted, enter the password botoxmoa123. note that the password is case sensitive. enter a valid e-mail to send this qr code or click to download. please ensure that qrcode@allergancongressposters.com has been added to your safe senders list or spam filter. scan to obtain pdf of poster fc17posterallergandayansimultaneoustx.pdf microsoft word july 2020 cmr-idr 936 proof final.docx skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 312 in-depth reviews photodynamic therapy in 2020: lights in the darkness neal bhatia, md1 1director of clinical dermatology, therapeutics clinical research, san diego, ca as 2020 continues to be the most chaotic year in recent history, and as dermatology practices open up again, the realization that the mechanisms of skin carcinogenesis did not stop for the quarantine are beginning to show up. dermatologists can agree that actinic keratoses (aks) do not believe in social distancing even though they can hide behind a mask. all joking aside, now that treatment options that could create open wounds are no longer on hold, photodynamic therapy for aks, nmsc, acne, and other uses can be safely performed with proper management of expectations, local skin reactions, and combinations with topical treatments. to be clear to those with questions, pdt itself does not increase risks for contracting any infection, let alone from the coronavirus, but attention to cleaning and sterilizing between treatments is essential for patient safety. fundamentals of photodynamic therapy as a reminder, or for those not familiar with the mechanisms of action of photodynamic therapy (pdt), the three essential components are: 1) a photosensitizer concentrated in target tissue, which in the us market is aminolevulinic acid (ala) delivered 10% in gel or 20% in stick background + updates introduction photodynamic therapy (pdt) is an integral treatment modality for treating the entire process of photodamage, based on what is understood about the pathogenesis of actinic keratosis and the consequences from treating only visible spots and not the underlying disease. dermatologists must consider incorporation of treatment in combination with duration, frequency, and tolerability of local skin reactions. these considerations are important, along with the combination of topical therapies and intermittent cryotherapy of individual actinic keratoses. aside from costs and patient demographics, adaptation by dermatologists can influence variability in long-term treatment algorithms. there are multiple published guidelines and consensus statements for the us and europe to promote safe incorporation of both blue and red light along with the variable concentrations of ala by dermatologists. however, there is a lack of head to head studies and comparative superiority as well as any evidence to support the use of topical agents. as management of local skin reactions becomes more commonplace, so will improved management of pdt to foster patient safety. abstract skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 313 preparations; 2) a light source of variable wavelength and energy (bf-rhodoled® is an led lamp emitting red light at a wavelength of 635 nm, blu-u wavelength occurs at 417 ±5 nm); and 3) oxygen available for conversion into reactive oxygen species.1 of note, the duration of action of the free oxygen radicals is about 40 nanoseconds, but, once the impact on tissue is made, the key for successful treatment involves optimal time and temperature. that said, other light sources are being regularly studied. evidence supporting the use of low fluence illumination compatible with activation spectra of porphyrins led to a pilot study in israel involving 15 patients ages 45-74. in the trial, one treatment using 20% ala cream under occlusion for 3-4 hours followed by 45 minutes exposure with red led traffic lamp 625 nm bulbs led to a tolerable treatment with minimal pain. moreover, only 2 of 15 patients needed two treatments with no recurrences reported after 3 months. however, the verdict is still out on efficacy for sbcc and scc in situ and other indications. once the mechanisms are understood and the equipment is in place, the right patient has to be screened and educated about the role of therapy and potential outcomes. the staff needs to review any oral medications as well as any topical prescription or nonprescription products on the patient’s face or scalp. in addition, the medical status of patient, the size, location, number and duration of aks/tumors, as well as the evolution of the growth pattern, are all essential historical considerations. in addition, timing is critical with treatments, as the patient must not have any upcoming social events, photo sessions, or vacations. the patient must also be committed to staying indoors and out of the sun for the necessary amount of time to protect against exuberant responses. furthermore, make sure that the procedure is not scheduled on the same day as a flight, a golf outing, a wedding, or anything else except hibernation. the staff and the office have to be just as prepared. there needs to be adequate training on the procedure’s dynamics, as well as making sure enough treatment time is allotted on everyone’s schedule to manage pre and post-treatment expectations and provide sufficient counseling. incorporation of all available methods for pain control is a must. fans, mist sprays, cool packs, and a hand to hold are important for the first few minutes for treatment. there is a solid rationale for microneedling prior to treatment despite the lack of reimbursement or a coding algorithm. in a randomized, single-blinded, split-face controlled trial, 32 patients were treated either with a 10-min or 20-min incubation using ala-blu pdt after pretreatment with either a microneedle (200 um) or sham roller; which was blinded to laterality in an attempt to measure ak resolution and assess pain associated with microneedle pretreatment.3 the group treated with 20minute incubation experienced ak clearance of 76% vs 58% on the sham side (p < .01) the pain assessment was not significantly different between the microneedle and sham sides (0.7 and 0.4; p = 0.28), respectively. the authors concluded that pdt with microneedle pretreatment at a 20-minute ala incubation time significantly improved ak clearance and the procedure was virtually painless, but a 10-minute ala incubation time did not reach significantly different ak clearance.3 time and temperature the labelled indication for 20% ala with blue light calls for an incubation of 14 hours, meaning treat the day before and stay skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 314 indoors to avoid activating the light.4 ironically, these treatments were indicative of how daylight pdt was conducted, given that the patients who had ala applied the day before would immediately start reacting once they went outdoors to come back to the clinic for the light treatment. in reality, despite the multitude of published variations of incubation times that have been accepted as options, there is data exploring the logarithmic conversion of ala as measured in an actinic keratosis papule. in a study of 20 patients examining surface ppix, measurements were taken using a handheld fiber optic–based fluorescence dosimeter. examination of the fluorokinetics was measured at 60% at one hour but 100% at two hours.5 although the correlation was not compared with clinical efficacy of treatment, it does suggest the potential for issues with absorption and possibly makes a case for longer incubation times for improved clearance. on the other hand, a recently published study examined the concept of "simultaneous pdt." in this bilaterally controlled, intrapatient study of 23 patients, 20% ala was applied to the entire face and/or scalp. on one side blue light was started immediately and continued for either 30, 45, or 60 minutes while on the contralateral side, blue light began 1 hour after ala application and lasted 1000 sec ("conventional pdt"). pain was evaluated on a 0-10 scale and ak counts were determined by clinical exam and photography. all patients experienced significantly less pain during simultaneous illumination than during conventional pdt 3 months post-treatment, and clearance was nearly identical on the two sides (noninferiority ± 15% margin). the conclusions suggested that the “simultaneous pdt” regimen is essentially painless with efficacy similar to conventional pdt.6 although the study was relatively small, and additional studies were recommended, the practical aspects of having bulbs illuminated for extended periods could prove financially prohibitive. coding updates for 2020 the cpt codes for photodynamic therapy have been updated to reflect the definition of the procedure: photodynamic therapy by external application of light to destroy premalignant and/or malignant lesions of the skin and adjacent lip mucosa by activation of photosensitive drug(s), each phototherapy exposure session. the previous code in use was 96567, which should now be used only when a physician does not directly participate in the pdt treatment delivery. dermatologists should now use the two codes 96573 and 96574. the 96573 code is to be utilized when the physician or other practicing clinician applies the photosensitizer and initiates the light illumination, while 96574 is used when curettage or debridement of the individual actinic keratoses is performed with the procedure.7 the code means applying the ala and turning on the light but not necessarily staying in the room the entire time with the patient; however, remaining present is good practice to improve the patient’s outcomes, as talkesthesia and hand-holding can make the experience better and ensure that a second treatment in the cycle can be considered. daylight pdt: realistic options in europe the concept of using daylight as the light source with methyl-aminolevulinic acid was studied using multiple parameters. the first major study published in 2008 compared the efficacy and tolerability of daylight pdt to red light pdt both using mal, based on the continuous and sustained activation of protoporphyrin ix by skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 315 daylight as compared to the concentrated activation by red light. in this trial, 29 patients with aks on the head were treated with mal-pdt then divided into one area illuminated by red led light (37 j cm(-2)) after 3-h incubation with mal under occlusion, compared to the other side where mal cream was applied under occlusion for 30 minutes then treated in the daylight for 2.5 hours. the investigators reported no significant difference in efficacy between the two treatments (p = 0.13), (79% in the daylight area vs 71% in the led area), but there was more pain reported on the side with illumination using led than daylight (p < 0.0001). local skin reactions were similar on both sides. the observations made about shorter incubation time in the office and the efficacy demonstrated by continuous activation of porphyrins by daylight offered convenience and tolerability.8 since then, many studies have evaluated daylight pdt using variations in concentrations of mal,9 exposure times,10 and impact of ak thickness,11 all of which led to the conclusions of high tolerability with comparable efficacy to conventional treatments. of note, these treatments were performed under any time of day or condition except when it rained. the patients were to use a sunscreen of spf 20, treated with curettage and application of mal followed by daylight exposure within 30 minutes. after 2 hours of daylight the mal cream was removed and the patients remained outdoors for the remainder of the day.10,11 the risks of recurrences with daylight pdt were evaluated in a study in 2019 comparing a nanoemulsion gel containing 7.8% 5-aminolaevulinic acid to 16% mal cream. there were 52 patients who underwent one daylight pdt session with either photosensitizer and followed for both 12 weeks and one year. after 12 weeks from one treatment, almost 80% of the aks treated with bf-200 ala gel and 76.5% of the lesions treated with mal cream were completely cleared. however, the recurrence rates 1 year after treatment were 19.9% for the bf-200 ala arm compared to 31.6% for patients treated with mal.12 a small pilot study using daylight pdt for actinic cheilitis was performed in israel with 11 patients (3 females, 8 males) with mean age of 59. each patient underwent a biopsy to confirm the diagnosis and exclude the presence of scc, which was repeated at the end of the study. the protocol mandated 2-3 treatments with each patient applying sunscreens, followed by curettage of lip aks and application of a thick layer of mal cream without occlusion. the patients were then exposed to 2-3 hours of sunlight between 8-11 am and then remained indoors. the investigators reported a response rate of 91% while patients reported mild erythema and minimal to no pain during treatment along with improved cosmetic outcomes.13 ironically, as the labelled indication for 20% ala/blue light calls for a 14 hour incubation,4 this is actually a modified version of daylight pdt since the patients were treated the day before and were exposed to the morning sun the following day. following what we know about pdt, the resumed reactions were probably somewhat painful, although that data does not exist. the low pain potential and convenience of daylight pdt are compelling but unlike practices in countries with socialized medicine, the inherent obstacles for treatment with daylight pdt are multiple…the most glaring being the lack of predictable local skin reactions with this offlabel method of pdt, as standardization of an algorithm continues to be developed. skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 316 aside from the obvious counter arguments to the use of daylight pdt in the us market, the lack of a cpt code that supports reimbursement of this procedure and the risk of financial obligation for the photosensitizing agent make incorporation into regular private practice difficult. conversely, an opportunity exists to offer the procedure to patients who pay out of pocket or have high deductibles that also want to avoid the pain of the treatment, as long as there is appropriate monitoring of skin reactions and proper consent is obtained. table 1. methods to improve outcomes with pdt optimizing combinations many options for using topical therapies for actinic keratoses have been published and adapted into practice (table 1), primarily to reduce the risks of progression to scc as well as to possibly serve as chemoprevention with the procedure.14,15 one study involving 17 patients involved treatment on one side of the body, either the face, scalp, forearms, with topical 5% 5-fu cream as pretreatment for 6 days, with no pretreatment on the other side. both sides were incubated for 3 hours with mal 16% cream and protoporphyrin ix (ppix) levels were measured by noninvasive fluorimetry and skin biopsy. after red light illumination, lesion clearance was assessed at 3, 6, 9, and 12 months after pdt with red light. the study showed that ppix levels were increased 2to 3-fold in 5-fu pretreated aks versus the control sides with relative clearance rates after pdt 75% versus 45% without 5fu pretreatment. the mechanisms of ak clearance were thought to be the enhanced photosensitizer accumulation and p53 induction from 5fu, and in a combined regimen could be easily integrated to reduce the recurrence of aks and potentially reduce skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 317 the risk of scc.15 similar pilot studies have been performed with imiquimod 5% cream between cycles as well as with cryotherapy, opening the door for options for dermatologists to treat the entire process.14 modifications during the pandemic the conditions surrounding the pandemic from coronavirus lead to concerns about exposures of the same equipment to patients. after consultations with the manufacturers of the light devices, their recommendations are as follows (table 2, table 3): table 2. blue light: warning: turn power off and disconnect the power cord before cleaning the machine. caution: never immerse machine in liquids. do not use abrasive materials to clean the machine. do not allow water to enter this device. do not clean the inside of this device. the exterior surface of the blu-u® may be wiped down with a mild disinfectant or isopropyl alcohol. dry with a clean dry cloth. the outside surface of the plastic shield may be wiped down with a mild disinfectant or isopropyl alcohol. dry with a clean dry cloth. if goggles are used for eye protection, their surface may be wiped down with a mild disinfectant or isopropyl alcohol after each use. currently, 62% or higher isopropyl alcohol is sufficient to kill covid-19. -courtesy of lindsay habeeb, md medical affairs, associate director sunpharma; per cleaning instructions from the blu-u user manual (page 21): cleaning/disinfecting skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 318 table 3. red light: place replaceable plastic wrap around the user interface on rhodoled; staff should use gloves anytime touching, adjusting, or moving the device. clinic staff should use more conservative ppe protective measures (i.e., face shield) when applying ala gel to patient's face, always use gloves to apply ala (as they should have been doing all along) use occlusion on face (per ameluz label) so the patient can incubate with photosensitizer and keep office staff safe with patient keeping mask on while incubating; the occlusion serves as barrier to keep mask from touching the ala (and occlusion prevents risk of mask redistributing ala to mucous membranes) re: lsrs post pdt, recommend to patients to stay indoors out of light per label and clean hands before & after applying any sunscreens or post-pdt occlusives to speed up recovery. -courtesy of jon lyons, phd, mba director, medical affairs – i.s. biofrontera, inc. communications regarding ameluz/rhodo-led skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 319 the versatility of photodynamic therapy using various light sources, photosensitizers in different concentrations and vehicles, and in combination with various strategies will provide many options for dermatology patients with aks, nmsc, acne vulgaris, and other conditions. in addition, the potential for incorporation of daylight pdt into practice can open doors for patients who were once reluctant to treatment, thereby reducing skin cancer risks. important anecdotal pearls include not shortchanging incubation times for convenience, especially for treating the extremities, optimizing every adjunct for pain control except steroids, including even a little alprazolam to reduce anxiety. many experts would agree that pdt is probably one of the best chemoprevention strategies in addition to being an effective field treatment. as you can see, pdt has a bright future regardless of which light is turned on. conflict of interest disclosures: dr. bhatia is an advisor, consultant, and investigator for biofrontera us and sunpharma funding: none corresponding author: neal bhatia, md director, clinical dermatology therapeutics clinical research 9025 balboa avenue, suite 105 san diego, ca 92123 phone: 858-571-6800 fax: 858-571-6801 email: bhatiaharbor@gmail.com references: 1. gold, m, “photodynamic therapy in dermatology,” new york: springer science, 2011 2. enk, cd. levi a, “low-irradiance red led traffic lamps as light source in pdt for actinic keratoses,” photodermatology, photoimmunology and photomedicine, dec 2012, vol 28, issue 6 pages 332-334 3. petukhova ta, hassoun la, foolad n, barath m, sivamani rk, “effect of expedited microneedleassisted photodynamic therapy for field treatment of actinic keratoses: a randomized clinical trial.,” jama dermatol. 2017;153(7):637–643. doi:10.1001/jamadermatol.2017.0849 4. physician’s insert, levulan kerastick® 5. warren c. et al. “noninvasive fluorescence monitoring of protoporphyrin ix production and clinical outcomes in actinic keratoses following short-contact application of 5-aminolevulinate,” journal of biomedical optics. 2010; 9/10 15(5) 6. kaw u, ilyas m, bullock t, rittwage l, riha m, vidimos a, hu b, warren cb, maytin ev, “a regimen to minimize pain during blue light photodynamic therapy of actinic keratoses: bilaterally controlled, randomized trial of simultaneous versus conventional illumination,” j am amer dermatol (2019), doi: https://doi.org/10.1016/j.jaad.2019.09.010 7. https://www.cms.gov/medicare-coveragedatabase/details/ncddetails.aspx?ncdid=128&ncdver=3&coverages election=both&articletype=all&policytype=final &s=all&keyword=photodynamic+therapy&key wordlookup=title&keywordsearchtype=and& bc=gaaaabaaaeaaaa%3d%3d& 8. wiegell sr, haedersdal m, philipsen pa, et al: “continuous activation of ppix by daylight is as effective as and less painful than conventional photodynamic therapy for actinic keratoses; a randomized, controlled, single-blinded study,” br j dermatol 2008; 158:740-746. 9. wiegell sr, haedersdal m, eriksen p, wulf hc, “photodynamic therapy of actinic keratoses with 8% and 16% methyl aminolaevulinate and homebased daylight exposure: a double-blinded randomized clinical trial,” br j dermatol. 2009; 160(6):1308-1314. 10. wiegell sr, fabricius s, stender im, et al, “a randomized, multicentre study of directed daylight exposure times of 1½ vs. 2½ h in daylight-mediated photodynamic therapy with methyl aminolaevulinate in patients with multiple thin actinic keratoses of the face and scalp,” br j dermatol 2011;164:1083-1090. 11. wiegell sr, fabricius s, gniadecka m, et al. “daylight-mediated photodynamic therapy of moderate to thick actinic keratoses of the face and scalp: a randomized multicentre study. br j dermatol. 2012; 166(6):1327-1332. conclusion skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 320 12. dirschka t, ekanayake-bohlig s, dominicus r, et al, “a randomized, intraindividual, non-inferiority, phase iii study comparing daylight photodynamic therapy with bf-200 ala gel and mal cream for the treatment of actinic keratosis,” j eur acad dermatol venereol. 2019;33(2):288-297.. 13. levi, a et al, “daylight photodynamic therapy for the treatment of actinic cheilitis,” photodermatology, photoimmunology & photomedicine, january 201, volume35, issue1 14. serra-guillen c, nagore e, hueso l, et al, “a randomized comparative study of tolerance and satisfaction in the treatment of actinic keratosis of the face and scalp between 5% imiquimod cream and photodynamic therapy with methyl aminolaevulinate, “br j dermatol. 2011; 164(2):429-433. 15. maytin ev, anand s, riha m, et al. “5fluorouracil enhances protoporphyrin ix accumulation and lesion clearance during photodynamic therapy of actinic keratoses: a mechanism-based clinical trial,” clin cancer res, 2018; 24(13):3026-3035. table 2 courtesy lindsay habeeb, md medical affairs, associate director sunpharma per cleaning instructions from the blu-u user manual (page 21): cleaning/disinfecting table 3 courtesy jon lyons, phd mba director, medical affairs u.s. biofrontera, inc. communications regarding ameluz/rhodo-led patient satisfaction with tildrakizumab treatment in a phase 4 real-world study of tildrakizumab in patients with moderate-to-severe plaque psoriasis neal bhatia1, j gabriel vasquez2, brad schenkel3, jayme heim2 1therapeutics clinical research, san diego, ca, usa; 2west michigan dermatology, grandville, mi, usa; 3sun pharmaceutical industries, inc., princeton, nj, usa introduction • psoriasis is a chronic, systemic, inflammatory disorder that significantly impairs patients’ physical and psychosocial well-being1 • treatment dissatisfaction among patients with moderate-to-severe psoriasis is a concern in clinical settings1,2 • tildrakizumab is an anti–interleukin-23 p19 monoclonal antibody approved for the treatment of moderate-to-severe plaque psoriasis in patients who are candidates for systemic therapy or phototherapy3 • limited data are available on patient satisfaction with tildrakizumab treatment in real-world settings objective • to report overall patient satisfaction with specific aspects of treatment in patients with moderate-to-severe plaque psoriasis after 64 weeks of treatment with tildrakizumab under real-world conditions methods study design and population • this was a phase 4, 64-week, uncontrolled, open-label, real-world study (figure 1) figure 1. study design uncontrolled, open-label, single-arm, multicenter study (nct03718299) treatment and follow-up screening (n = 60) enrollment (n = 55) key criteria inclusion • male or female • ≥18 years • moderate-to-severe plaque psoriasisa • candidates for phototherapy or systemic therapy • no active or untreated latent tuberculosis exclusion • erythrodermic psoriasis • only pustular, guttate, or inverse psoriasis • other skin conditions that could interfere with evaluation screening and enrollment study visit injection screening x week: 0/baseline x x 4 x x 8 x 12 x 16 x x 20 24 28 x x 32 36 40 x x 44 48 52 x x 64 treatment • tildrakizumab 100mg administered at weeks 0 (baseline), 4, 16, 28, 40, and 52 • administered by a healthcare provider patient satisfaction evaluation (itt population, n = 55) tsqm • effectiveness • side effects • convenience • global satisfaction tildrakizumab overall satisfaction • improvement in symptom • speed of improvement • frequency of dosing • side effects happiness with psoriasis control absa ≥3%. bsa, body surface area; itt, intention-to-treat; tsqm, treatment satisfaction questionnaire for medication. assessments • patient satisfaction was evaluated using — the treatment satisfaction questionnaire for medication (tsqm),4 administered at all postbaseline visits ○ the tsqm includes effectiveness, side effects, convenience, and global satisfaction domains — the tildrakizumab overall satisfaction scale, administered at all postbaseline visits ○ this instrument includes improvement in symptoms, speed of improvement, frequency of dosing, and side effects domains — the patient happiness with psoriasis control instrument, administered at baseline and all postbaseline visits — for all measures, higher scores indicate greater satisfaction statistical analysis • the intention-to-treat population was used for patient satisfaction analysis and included all patients who enrolled and were assigned to receive tildrakizumab • changes from baseline in happiness with psoriasis control were analyzed using student’s t-tests — missing data were not imputed results patient demographics • of 55 patients enrolled, 45 were assessed at week 64 (end of study) • the majority of patients were male (28/55; 50.9%) and white (52/55; 94.5%), with a mean ± standard deviation (sd) age of 48.6 ± 15.3 years (table 1) table 1. demographic and baseline characteristics characteristic tildrakizumab(n = 55) sex female 27 (49.1) male 28 (50.9) race white 52 (94.5) black or african american 2 (3.6) asian 1 (1.8) ethnicity hispanic or latino 5 (9.1) not hispanic or latino 50 (90.9) age, years, mean ± sd 48.6 ± 15.3 happiness with psoriasis control, mean ± sd 2.7 ± 2.3 itt population. data shown as n (%) unless otherwise noted. itt, intention-to-treat; sd, standard deviation. figure 2. mean tsqm domain scores through week 64 effectiveness side effects convenience global satisfaction 0 25 50 75 100 125 150 79.5 79.2 82.2 81.978.7 77.1 85.2 81.776.5 81.3 85.1 80.559.5 70.8 83.3 72.7 m ea n ± s d t s q m s co re week 4 week 28 week 52 week 64 n = 55 53 48 45 6 3 3 3 55 53 48 45 55 53 48 45 itt population. error bars represent the sd. itt, intention-to-treat; tsqm, treatment satisfaction questionnaire for medication; sd, standard deviation. • the mean ± sd tildrakizumab overall satisfaction domain scores increased from 6.0 ± 2.4 to 8.7 ± 2.0 for improvement in symptoms, 5.9 ± 2.4 to 8.3 ± 2.3 for speed of improvement, 7.8 ± 2.1 to 9.1 ± 1.7 for frequency of dosing, and 8.6 ± 2.1 to 9.6 ± 0.7 for side effects (figure 3) figure 3. mean tildrakizumab overall satisfaction domain scores through week 64 improvement in symptoms speed of improvement frequency of dosing side effects 0 5 10 15 8.7 8.3 9.1 9.68.4 7.9 8.6 9.58.0 7.8 8.3 9.16.0 5.9 7.8 8.6 n = 55 53 48 45 55 53 48 45 55 53 48 45 55 53 48 45 m ea n ± s d o ve ra ll s at is fa ct io n sc or e week 4 week 28 week 52 week 64 itt population. error bars represent the sd. itt, intention-to-treat; sd, standard deviation. figure 4. mean happiness with psoriasis control score from baseline through week 64 0 5 10 15 week 8.5 8.48.2 6.4 2.7 4548535555n = *** * bl 4 28 52 64 m ea n ± s d h ap pi ne ss w ith p so ri as is c on tr ol s co re itt population. error bars represent the sd. *p <0.01; statistically significant change from baseline based on student’s t-test. itt, intention-to-treat; sd, standard deviation. conclusions • patients with moderate-to-severe plaque psoriasis treated with tildrakizumab in a real-world setting reported improvements in overall satisfaction and across all domains assessed references 1) duffin kc, et al. br j dermatol. 2014;170(3):672–80. 2) armstrong aw, et al. jama dermatol. 2013;149(10):1180–85. 3) ilumya® (tildrakizumab-asmn) injection 100 mg/ml. full prescribing information. cranbury, nj; sun pharmaceutical industries, inc., 2022. 4) atkinson mj, et al. health qual life outcomes. 2004;2:12. acknowledgments we thank the patients for their participation and dr. stephen j rozzo for contributions to the study. this study was funded by sun pharmaceutical industries limited. medical writing support was provided by nitish chaudhari, phd, of alphabiocom, llc, and funded by sun pharma. disclosures nb is an advisor, consultant, and investigator for abbvie, almirall, arcutis, biofrontera, bms, brickell, dermavant, epi health, ferndale, galderma, genentech, incyte, isdin, j&j, laroche-posay, leo, lilly, novartis, ortho, pfizer, p&g, regeneron, sanofi, stemline, sun pharma, and verrica. jgv reports nothing to disclose. bs is an employee of sun pharmaceutical industries, inc. jh is a speaker, advisor, and consultant for amgen, abbvie, celgene, eli lilly, janssen, and novartis; an advisor for galderma, mayne, and sanofi regeneron; an advisor and consultant for ortho dermatologic; and a speaker and advisor for sun pharma. • for the happiness with psoriasis control instrument, the mean ± sd score increased from 2.7 ± 2.3 at baseline to 8.5 ± 2.5 at week 64, corresponding to “extremely happy” (p <0.001 from week 4 through week 64; figure 4) efficacy • from week 4 to week 64, the mean ± sd tsqm domain scores increased from 59.5 ± 17.0 to 79.5 ± 20.1 for effectiveness and 72.7 ± 18.6 to 81.9 ± 20.5 for global satisfaction, respectively. the convenience score remained stable from week 4 to week 64 (83.3 ± 15.9 to 82.2 ± 16.4, respectively), and ≤6 patients reported side effects (figure 2) presented at fall clinical dermatology conference 2019 | las vegas, nv, usa | 17–20 october, 2019 previously presented at the 6th congress of the skin inflammation & psoriasis international network background • plaque psoriasis (pso) is an immune-mediated, inflammatory disease that affects around 3% of adults in the united states.1,2 • the fc-free, pegylated, anti-tumor necrosis factor (tnf) biologic certolizumab pegol (czp) was approved by the fda for moderate to severe pso in 2018,3 and has shown a safety profile consistent with the anti-tnf class in adults with pso over 48 weeks in phase 3 trials.4,5 • here, we report cumulative safety data over 96 weeks from the czp in pso phase 3 clinical development program. methods patients and study design • safety data, pooled across studies, are presented for patients who received ≥1 dose of czp during the first 96 weeks of the cimpasi-1 (nct02326298), cimpasi-2 (nct02326272), and cimpact (nct02346240) phase 3 studies (figure 1). • only 11 placebo-randomized patients continued on placebo after week 16; placebo data are presented to week 16 only. • patient inclusion criteria: ≥18 years of age, moderate to severe pso ≥6 months with psoriasis area severity index (pasi) ≥12, ≥10% body surface area (bsa) affected, physician’s global assessment (pga) ≥3 on a 5-point scale; candidates for systemic pso therapy, phototherapy, and/or photochemotherapy. • exclusion criteria: previous treatment with czp or >2 biologics; previous treatment with etanercept (etn) (cimpact only); treatment with etn within the first 12-weeks of enrolment (cimpasi-1 and cimpasi-2 only); history of primary failure to any biologic or secondary failure to >1 biologic; erythrodermic, guttate or generalized pso types; current or history of chronic or recurrent viral, bacterial or fungal infections. safety assessments • adverse events (aes) and serious adverse events (saes) were classified using meddra version 18.1. • an sae was defined as an ae meeting one or more of the following criteria: leading to death, life-threatening, leading to significant or persistent disability/incapacity, congenital anomalies/birth defects, an important medical event (based upon medical judgement) or leading to initial or prolonged inpatient hospitalization. • incidence rates (ir) were calculated as incidence of new cases per 100 patient-years (py). results patient population • across all 3 studies, 995 patients received ≥1 dose czp through weeks 0–96. • total exposure to czp was 1,471 py. • baseline characteristics were well-balanced between treatment groups (table 1). incidence of aes and saes • at week 16, the ir of aes within both the czp 400 mg every two weeks (q2w) and czp 200 mg q2w dose groups was comparable to that of placebo (table 2). references 1. kurd sk and gelfand jm. jaad 2009;60:218–24; 2. rachakonda td. et al. 2014;70:512–6; 3. certolizumab pegol prescribing information. available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/125160s270lbl. pdf [last accessed: may 2019]; 4. gottlieb ab. et al. jaad 2018;79:302–14.e6; 5. lebwohl m. et al. jaad 2018;79:266–76.e5. author contributions substantial contributions to study conception/design, or acquisition/ analysis/interpretation of data: ab, bs, rl, sk, ca, mb, ml, kr; drafting of the publication, or revising it critically for important intellectual content: ab, bs, rl, sk, ca, mb, ml, kr; final approval of the publication: ab, bs, rl, sk, ca, mb, ml, kr. author disclosures ab: consulting honoraria and clinical investigator: abbvie, aclaris, akros, allergan, almirall, amgen, arena, boehringer ingelheim, bristol-myers squibb, celgene, dermavant, dermira inc., eli lilly, galderma, genentech/ roche, gsk, janssen, leo pharma, meiji, merck, novartis, pfizer, purdue pharma, regeneron, sandoz, sanofi genzyme, sienna pharmaceuticals, sun pharma, ucb pharma, valeant, vidac. speaker’s fees: eli lilly, janssen, regeneron, sanofi genzyme; bs: consulting fees and/or other honoraria: abbvie, almirall, amgen, astrazeneca, boehringer ingelheim, celgene, dermira inc., janssen, eli lilly, leo pharma, medac, menlo therapeutics, novartis, pfizer, gsk, ucb pharma, sun pharma, ortho dermatologics/ valeant, regeneron, sanofi genzyme; corrona psoriasis registry; grant support to the university of connecticut for fellowship program (payments to the university of connecticut, not bs): abbvie, janssen; rl: consulting fees and/or other honoraria: abbvie, amgen, boehringer ingelheim international gmbh, centocor, pfizer, janssen, leo pharma, eli lilly, valeant; sk, ca, mb: employees of ucb pharma; ml: consultant for allergan, aqua, leo pharma, promius. employee of mount sinai which receives research funds from abbvie, amgen, boehringer ingelheim, celgene, eli lilly, janssen/johnson & johnson, kadmon, medimmune/ astra zeneca, novartis, pfizer, valeant, vidac; kr: advisor and/or paid speaker and/or clinicall investigator for abbvie, affibody, amgen, biogen, boehringer ingelheim, celgene, centocor, covagen, forward pharma, gsk, janssen-cilag, kyowa kirin, leo pharma, eli lilly, medac, merck sharp & dohme corp., novartis, ocean pharma, pfizer, regeneron, samsung bioepis, sanofi, takeda, ucb pharma, valeant, xenoport. acknowledgements the studies were funded by dermira inc. in collaboration with ucb pharma. ucb is the regulatory sponsor of certolizumab pegol in psoriasis. we thank the patients and their caregivers in addition to the investigators and their teams who contributed to this study. the authors acknowledge bartosz łukowski, msc, ucb pharma, brussels, belgium for publication coordination and amelia frizell-armitage, phd, costello medical, cambridge, uk, for medical writing and editorial assistance. all costs associated with development of this poster were funded by ucb pharma. since conducting this work kr has moved institute and is now affiliated with skinflammation® center, hamburg, and dermatologikum berlin, berlin, germany. conclusions • the overall incidence of aes and saes of interest was low and the ir of saes was comparable between the two dose groups. • risk did not increase with longer exposure. • no new safety signals were identified compared with previous studies in czp. • the safety profile of czp dosed at both 400 mg and 200 mg q2w was consistent with the anti-tnf class in pso. objective • to report cumulative 96-week safety data from three phase 3 trials of certolizumab pegol in plaque psoriasis. safety of certolizumab pegol in plaque psoriasis: pooled 96-week data from three phase 3, multicenter, randomized, placebo-controlled studies (cimpasi-1, cimpasi-2 and cimpact) a. blauvelt,1 b. strober,2,3 r. langley,4 s. kavanagh,5 c. arendt,6 m. boehnlein,7 m. lebwohl,8 k. reich9 1oregon medical research center, portland, or, usa; 2university of connecticut health center, farmington, ct, usa; 3probity medical research, waterloo, ontario, canada; 4dalhousie university, nova scotia, canada; 5ucb pharma, raleigh, nc, usa; 6ucb pharma, brussels, belgium; 7ucb pharma, monheim, germany; 8icahn school of medicine at mount sinai, new york, ny, usa; 9sciderm research institute, hamburg, and dermatologikum berlin, germany figure 1. cimpasi-1, cimpasi-2 and cimpact study design • the ir of aes did not increase over time to week 96 for patients receiving czp (table 2). • at week 96, the ir of saes was comparable between the two czp dose groups (table 3). selected aes and saes of interest • at week 96, the overall incidence of selected aes and saes of interest was low (table 3). • there were 4 deaths, 1 of which in the czp 200 mg q2w dose group was assessed by the investigator as related to the study drug (table 3). • there were no reports of serious skin disorders such as steven johnson or lupus. aloading dose of czp 400 mg q2w at weeks 0, 2 and 4 or weeks 16, 18 and 20; bdepending on pasi response, any dose adjustments were either mandatory or at the discretion of the investigator. bw: twice per week; czp: certolizumab pegol; etn: etanercept; ld: loading dose; pasi: psoriasis area severity index; q2w: every two weeks; q4w: every four weeks. table 1. pooled demographics and baseline characteristics for patients who received ≥1 dose czp through weeks 0–96 apatients who received both czp 200 mg q2w and czp 400 mg q2w are only included once in the population count for the ‘all czp’ group. bmi: body mass index; czp: certolizumab pegol; il: interleukin; pasi: psoriasis area severity index; q2w: every two weeks; sd: standard deviation; tnf: tumor necrosis factor. table 2. cumulative aes over time at weeks 16, 48 and 96 apatients who received both czp 200 mg q2w and czp 400 mg q2w are only included once in the population count for the ‘all czp’ group. ae: adverse event; ci: confidence interval; czp: certolizumab pegol; ir: incidence rate per 100 patient-years; q2w: every two weeks. table 3. overview of aes and saes to week 96 apatients who received both czp 200 mg q2w and czp 400 mg q2w are only included once in the population count for the ‘all czp’ group; bother commonly reported aes (≥5% patients) included arthalgia, headache, psoriasis and hypertension; ctwo each of pneumonia, erysipelas, and one each of abdominal abscess, appendicitis, escherichia sepsis, endophthalmitis, ovarian abscess, klebsiella pneumonia, bronchitis, bacteraemia, sepsis, tuberculosis, pyelonephritis, haematoma infection; dtwo cellulitis events and one each of gastroenteritis, pancreas infection, borrelia infection, bartholin’s abscess, varicella, infected bite, pneumonia, bronchitis, pyoderma, urinary tract infection; eone each of adenocarcinoma of the colon, anaplastic oligodendroglioma, prostate cancer, clear cell renal cell carcinoma; fone each of breast cancer, glioblastoma, hodgkin’s disease, laryngeal cancer, prostate cancer; gtwo basal cell carcinoma, one keratoacanthoma; hone craniocerebral injury and one multiple injuries, both assessed as unrelated to study drug; ione chronic obstructive pulmonary disease assessed as unrelated to study drug, one patient experienced distributive shock, cardiac arrest, hepatic failure and disseminated intravascular coagulation and death was assessed as related to the study drug by the investigator. ae: adverse event; ci: confidence interval; czp: certolizumab pegol; ir: incidence rate; py: patient-years; q2w: every two weeks; sae: serious adverse event; tnf: tumor necrosis factor. all czpa (n=995) czp 400 mg q2w (n=711) czp 200 mg q2w (n=726) patient and disease characteristics age, years, mean ± sd 45.6 ± 13.2 45.7 ± 13.0 45.3 ± 13.1 male, n (%) 652 (65.5) 463 (65.1) 487 (67.1) bmi, kg/m2, mean ± sd 30.4 ± 7.0 30.7 ± 7.2 30.2 ± 6.7 disease duration, years, mean ± sd 18.2 ± 12.5 18.3 ± 12.4 18.5 ± 12.6 pasi, mean ± sd 20.2 ± 7.8 20.2 ± 7.7 20.2 ± 7.8 prior treatment biologic therapy, n (%) anti-tnf anti-il-17 anti-il-12/il-23 299 (30.1) 122 (12.3) 149 (15.0) 49 (4.9) 219 (30.8) 87 (12.2) 106 (14.9) 42 (5.9) 219 (30.2) 91 (12.5) 109 (15.0) 30 (4.1) prior systemic therapy for psoriasis, n (%) 714 (71.8) 519 (73.0) 526 (72.5) n/n (%) ir (95% ci) all czpa czp 400 mg q2w czp 200 mg q2w placebo week 16 414/692 (59.8) 319.1 (289.1, 351.4) 217/342 (63.5) 348.3 (303.5, 397.9) 197/350 (56.3) 292.1 (252.8, 335.9) 97/157 (61.8) 342.6 (277.8, 417.9) week 48 709/962 (73.7) 219.6 (203.7, 236.4) 444/627 (70.8) 228.6 (207.8, 250.9) 321/460 (69.8) 221.2 (197.6, 246.7) week 96 820/995 (82.4) 172.7 (161.1, 184.9) 528/711 (74.3) 186.4 (170.9, 203.0) 514/726 (70.8) 161.4 (147.8, 176.0) all czpa (n=995) czp 400 mg q2w (n=711) czp 200 mg q2w (n=726) exposure (py) 1,471 700 772 total aes, ir (95% ci) total saes, ir (95% ci) 172.7 (161.1, 184.9) 9.2 (7.7, 10.9) 186.4 (170.9, 203.0) 10.8 (8.5, 13.7) 161.4 (147.8, 176.0) 7.7 (5.9, 10.0) most commonly reported aes (≥10% patients),b ir (95% ci) nasopharyngitis upper respiratory tract infection 19.0 (16.6, 21.6) 10.3 (8.6, 12.2) 21.8 (18.3, 25.9) 11.9 (9.4, 14.9) 19.4 (16.2, 23.1) 9.6 (7.4, 12.1) selected aes and saes of interest, ir (95% ci) serious infections active tuberculosis primary progressive multiple sclerosis congestive heart failure malignancies (excluding non-melanoma skin cancer) non-melanoma skin cancer 1.7 (1.1, 2.5) 0.1 (0.0, 0.4) 0.1 (0.0, 0.4) 0.1 (0.0, 0.4) 0.5 (0.2, 1.1) 0.2 (0.0, 0.6) 1.7 (0.9, 3.0)c 0.1 (0.0, 0.8) 0.1 (0.0, 0.8) 0.1 (0.0, 0.8) 0.6 (0.2, 1.5)e 0.4 (0.1, 1.3)g 1.6 (0.8, 2.7)d 0.0 0.0 0.0 0.7 (0.2, 1.5)f 0.0 discontinuations due to aes, ir (95% ci) severe aes, ir (95% ci) aes leading to death, ir (95% ci) 4.3 (3.3, 5.5) 7.4 (6.0, 9.0) 0.3 (0.1, 0.7) 5.5 (3.9, 7.5) 8.6 (6.5, 11.1) 0.3 (0.0, 1.0)h 3.4 (2.2, 5.0) 6.6 (4.8, 8.7) 0.3 (0.0, 0.9)i 0 16 484032week initial treatment period (double-blinded) lda czp 200 mg q2w czp 400 mg q2w 14496 open-label treatment placebo q2w lda czp 200 mg q2w czp 400 mg q2w ≥pasi 50 re-randomization initial treatment period (double-blinded) maintenance period (double-blinded) <pasi 50 – open-label treatment placebo q2w czp 400 mg q4w etn 50 mg bw washout lda czp 200 mg q2w czp 400 mg q2w czp 400 mg q2w czp 200 mg q2w placebo q2w <pasi 75 entered escape arm (czp 400 mg q2w) 12 czp 400 mg q2w czp 200 mg q2w ≥pasi 50 <pasi 50 open-label treatment 1: 2 :2 r a n d o m iz a ti o n 96 1440 16 484032week maintenance period (double-blinded) 1: 3 :3 :3 r a n d o m iz a ti o n ≥pasi 50, <pasi 75 <pasi 50 – withdrawn ≥pasi 50 <pasi 50 – withdrawn <pasi 50 – withdrawn <pasi 50 entered escape arm (czp 400 mg q2w) ≥pasi 50 open-label dose switchingb <pasi 75 <pasi 75 <pasi 75 <pasi 75 lda open-label dose switchingb a) cimpasi-1 and cimpasi-2 b) cimpact microsoft word september 2020 bar 868 proof.docx skin september 2020 volume 4 issue 5 copyright 2020 the national society for cutaneous medicine 452 brief articles an atypical presentation of pemphigus vegetans in the umbilicus antonio jimenez, bs1, paige hoyer, md2, michael wilkerson, md2 1the university of texas medical branch, school of medicine, galveston, tx 2the university of texas medical branch, department of dermatology, galveston, tx the word “pemphigus” is derived from the greek word “pemphix” or blister.1 pemphigus is a rare, blistering mucocutaneous disease. the pathogenesis of pemphigus involves the autoimmune destruction of desmosomal proteins–the bullous character of the disease is the result of the loss of intercellular connections. pemphigus is common in middle-aged adults aged 50-60.2 pemphigus vulgaris is the most common type of pemphigus, and it presents with oral erosions and flaccid bullae in the skin. the disease is chronic. a rare variant of pemphigus vulgaris is pemphigus vegetans. in contrast to pemphigus vulgaris, it most often presents with verrucous plaques in intertriginous and flexural areas. the rare presentation of the disease makes it a diagnostic challenge. we present a case of pemphigus vegetans in the umbilicus of a 38-year-old female. a 38-year-old african american female with a past medical history of behcet’s syndrome, presented to the dermatology clinic with a chief complaint of recalcitrant oral ulcers. she was diagnosed with behcet’s syndrome four years prior by her rheumatologist on the basis of her oral ulcers. at the time of her diagnosis, a full autoimmune serology workabstract pemphigus is a chronic, autoimmune bullous disease that affects the skin and mucous membranes. pemphigus vegetans is a rare variant of pemphigus and presents as oral ulcerations with associated verrucous lesions in intertriginous or flexural areas. a 38-year-old african american woman presented to the clinic with a chief complaint of oral ulcers. she carried a diagnosis of behcet’s disease and was referred by rheumatology for evaluation of treatmentresistant mucosal ulcerations. at the time of her dermatology visit, she also reported an enlarging umbilical mass that had been present for several months. further examination of the umbilical lesion identified an exophytic, vegetative mass. histologic assessment of the lesion identified acanthosis and acantholysis with dermal eosinophils consistent with pemphigus vegetans. a pemphigus antibody panel was done and resulted positive for igg desmoglein-3 antibodies. the patient was treated with prednisone and rituximab with improvement of her lesions. we present an atypical presentation of pemphigus vegetans involving the umbilicus. this diagnosis should be considered in patients who present with oral erosions and concomitant vegetative lesions, regardless of location or prior diagnoses. introduction case presentation skin september 2020 volume 4 issue 5 copyright 2020 the national society for cutaneous medicine 453 up was completed and resulted in a positive ana of 1:80 (anti-snrnp, anti-ssa, antidsdna negative). hla-b51 was negative. her flare-ups were previously well-controlled on azathioprine 50 mg and prednisone 10 mg; however, she now reported a 3-4-month history of persistent, painful oral ulcers. she was referred by rheumatology for further evaluation. she had no significant family or social history. at initial presentation to dermatology clinic her treatment regimen consisted of colchicine 0.6 mg three times per day, prednisone 10 mg daily, and adalimumab 40 mg/0.8 ml injections every 2 weeks. physical examination demonstrated ulcerated lesions along her lower lip, lower gingiva, and tongue. the patient also reported an umbilical lesion that had been present for several months and had slowly increased in size. the lesion was painful and would drain clear fluid. she denied change in bowel habits, bloating, or hematochezia. she said she had not applied any treatments to the lesion. a colonoscopy completed one-month prior was clear. physical examination demonstrated a firm, erythematous exophytic mass arising from the umbilicus with erosions throughout (fig 1a). serous drainage and fibrinous slough were also noted (fig 1b). histopathological evaluation revealed acanthosis and acantholysis with dermal eosinophils consistent with pemphigus vegetans. a pemphigus antibody panel was ordered and resulted positive for igg desmoglein-3 antibodies. indirect immunofluorescence demonstrated a cell surface igg titer of 1:5120 on monkey esophagus substrate and 1:320 on intact human skin substrate which was also consistent with pemphigus. the patient was treated with prednisone 60 mg daily, and her symptoms remained stable. she then underwent 2 courses of 1,000 mg rituximab infusions given 2 weeks apart and noted significant improvement in the size of the umbilical lesion and the number of oral ulcers. her prednisone dose was tapered off. after 1 year of clinical improvement, the patient noted worsening in the number of oral ulcers and reappearance figure 1. pemphigus vegetans. (a) a draining, vegetative plaque on the patient’s umbilicus. (b) the patient’s lesion after expression of serous fluid. a b skin september 2020 volume 4 issue 5 copyright 2020 the national society for cutaneous medicine 454 of the umbilical lesion. she was re-started on prednisone 80 mg and received 2 infusions of rituximab 900 mg 2 weeks apart. her oral ulcers had improved 1 week after her second round of infusions. per oncology, they will plan for another round of rituximab in 1 year if needed. pemphigus is the result of pathogenic autoantibodies against desmosome cadherins or desmoplakins. there are three main types: pemphigus vulgaris, pemphigus foliaceus, and paraneoplastic pemphigus. pemphigus vulgaris accounts for 70% of cases and is the result of autoantibodies against desmoglein-3 and/or desmoglein-1.4 the clinical presentation of the disease is an eruption of eroded, flaccid bullae in the skin often with painful mucosal ulcerations. pemphigus vulgaris is diagnosed by histology and immunofluorescence, with confirmatory serologic testing. histopathological assessment of a pemphigus blister demonstrates intraepidermal acantholysis of the basal layer; the characteristic “tombstone” appearance of keratinocytes can be observed.5 direct immunofluorescence (dif) demonstrates intercellular deposits of immunoglobulin g (igg) and/or c3 in a net-like pattern. a rare, vegetative variant of pemphigus vulgaris is diagnosed in 1-2% of cases.6 pemphigus vegetans is described as a heaped-up, papillomatous plaque localized in intertriginous and flexural areas including: axillary, inguinal, peri-anal, and inframammary folds.7 oral involvement is also present in a majority of reported cases. the pathogenesis of the disease is similar to pemphigus vulgaris; it is the result of autoantibodies against desmoglein-3, and/or desmoglein-1 and desmocollin-1, -2, and 3.8 there are two clinical subtypes of pemphigus vegetans, and they are differentiated by their initial presentation: neumann variant (flaccid bullae) and hallopeau variant (pustules); both later develop into vegetative plaques.9 the neumann subtype resembles pemphigus vulgaris in its morphological character and relapsing-remitting course. in contrast, the hallopeau subtype has a benign course with prolonged remission rates; it seldom mirrors the classic clinical presentation of pemphigus vulgaris.9 there are histopathological differences between pemphigus vegetans and pemphigus vulgaris; however, there are no observed differences between the neumann and hallopeau subtypes which are differentiated clinically. on histological examination, there is evidence of the prototypical supra-basal acantholysis and additional epidermal hyperplasia, papillomatosis, and eosinophilic intraepidermal abscesses.10 there are no differences between pemphigus vegetans and vulgaris on immunofluorescence. the rare presentation of the disease makes it a diagnostic challenge; thus, it is important to differentiate pemphigus vegetans from other vegetative diseases including pyoderma vegetans and pyodermatitis pyostomatitis vegetans. the mainstay of treatment is systemic glucocorticoids and/or immunosuppressive agents (e.g., rituximab, azathioprine, cyclophosphamide) for treatment-resistant disease.7 we present a 38-year-old african american female with biopsy-proven pemphigus vegetans on the umbilicus with mucocutaneous involvement. her oral lesions had been previously misdiagnosed as behcet’s disease in the past. to date, most reported cases of pemphigus vegetans have involved the scalp and intertriginous discussion conclusion skin september 2020 volume 4 issue 5 copyright 2020 the national society for cutaneous medicine 455 areas. this case highlights an atypical presentation of the disease, as the presentation of pemphigus vegetans in nonflexural areas is rare. this diagnosis should be considered in all patients with verrucous plaques and associated mucosal involvement. additionally, patients diagnosed with pemphigus vegetans should be considered for treatment with rituximab similarly to patients diagnosed with pemphigus vulgaris. conflict of interest disclosures: none funding: none corresponding author: paige hoyer, md 301 university blvd galveston, tx 77555 phone: 512-968-5742 email: pehoyer@utmb.edu references: 1. santoro fa, stoopler et, werth vp. pemphigus. dental clinics of north america. 2013;57(4):597-610. 2. kasperkiewicz m, ellebrecht ct, takahashi h, et al. pemphigus. nature reviews disease primers. 3. scully c, mignogna m. oral mucosal disease: pemphigus. british journal of oral and maxillofacial surgery. 2008;46(4):272-277. 4. joly p, litrowski n. pemphigus group (vulgaris, vegetans, foliaceus, herpetiformis, brasiliensis). clinics in dermatology. 2011;29(4):432-436. 5. calvanico nj, robledo ma, diaz la. immunopathology of pemphigus. journal of autoimmunity. 1991;4(1):3-16. 6. zaraa i, sellami a, bouguerra c, et al. pemphigus vegetans: a clinical, histological, immunopathological and prognostic study. journal of the european academy of dermatology and venereology. 2010;25(10):1160-1167. 7. markopoulos ak, antoniades dz, zaraboukas t. pemphigus vegetans of the oral cavity. international journal of dermatology. 2006;45(4):425-428. 8. marfatia y, ajbani a, mehta k. verrucous lesions over external genitalia as a presenting feature of pemphigus vegetans. indian journal of sexually transmitted diseases and aids. 2019;40(2):176. 9. downie jb, dicostanzo dp, cohen sr. pemphigus vegetans—neumann variant associated with intranasal heroin abuse. journal of the american academy of dermatology. 1998;39(5):872-875. 10. monshi b, marker m, feichtinger h, et al. pemphigus vegetans immunopathological findings in a rare variant of pemphigus vulgaris. journal der deutschen dermatologischen gesellschaft. 2009. powerpoint presentation the impact of tralokinumab on quality of life and school in patients aged 12–17 with atopic dermatitis: results from the phase 3 ecztra 6 trial amy s. paller1, jonathan i. silverberg2, h. chih-ho hong3, michael cork4, luis puig5, petra arlert6, azra kurbasic6, lise soldbro6, eric l. simpson7 1departments of dermatology and pediatrics, feinberg school of medicine, northwestern university, chicago il, usa; 2department of dermatology, george washington university, washington dc, usa; 3department of dermatology and skin science, university of british columbia and probity medical research, surrey, bc, canada; 4sheffield dermatology research, department of infection, immunity, and cardiovascular disease, the university of sheffield and sheffield teaching hospitals, nihr clinical research facility, sheffield, uk; 5department of dermatology, hospital de la santa creu i sant pau-universitat autònoma de barcelona, barcelona, spain; 6leo pharma, a/s, ballerup, denmark; 7department of dermatology, oregon health & science university, portland, or, usa • tralokinumab resulted in significantly greater adjusted cdlqi mean change vs placebo, and increased proportions of patients with cdlqi ≥6 • tralokinumab improved several patient-reported outcomes that encompass psychosocial effects of ad in this vulnerable paediatric age group, as measured by the cdlqi • tralokinumab had a substantial benefit on the impact of ad on subdomains in the cdlqi related to school/holiday at week 16 • there was a trend towards treatment benefit with tralokinumab vs placebo across multiple other psychosocial domains • the largest improvements in qol were seen in the tralokinumab 300 mg group conclusions references 1. bieber t. allergy. 2020;75:54–62; 2. tsoi lc, et al. j invest dermatol. 2019;139:1480–89; 3. popovic b, et al. j mol biol. 2017;429:208–19; 4. ng m, et al. australas j dermatol. 2018;59:e114-e17; 5. ghio d, et al. br j health psychol. 2021;26:214-31; 6. manjunath j, et al. j eur acad dermatol venereol. 2022;36:e346–e48; 7. wollenberg a, et al. presented at european society for pediatric dermatology 21st annual meeting 2022; 8. paller a, et al. presented at 2021 fall clinical dermatology conference 40th annual meeting. disclosures amy s. paller has served as an investigator for abbvie, anaptysbio, incyte, janssen, krystalbio, leo pharma, regeneron, and ucb, received honorarium for consultancy from abbvie, abeona, almirall, anaptysbio, arena, azitra, biomx, boehringer ingelheim, castle biosciences, catawba, dermira, exicure, forté, kamari, leo pharma, lilly, lifemax, novartis, pfizer, regeneron, sanofi genzyme, seanergy, and ucb, and served on a data safety monitory board for abbvie, bausch, galderma, and novan. jonathan i. silverberg is an investigator for abbvie, celgene, eli lilly and company, gsk, kiniksa, leo pharma, menlo therapeutics, realm therapeutics, regeneron, roche, and sanofi; a consultant for pfizer inc., abbvie, anacor, anaptysbio, arena pharmaceuticals, asana biosciences, dermira, dermavant, eli lilly and company, galderma, gsk, glenmark, incyte, kiniksa, leo pharma, medimmune, menlo therapeutics, novartis, realm therapeutics, regeneron, and sanofi; a speaker for regeneron and sanofi; and is on advisory boards for pfizer inc., dermira, leo pharma, and menlo therapeutics. h. chih-ho hong is a researcher, consultant, and/or advisor for abbvie, amgen, arcutis, bausch health, boehringer ingelheim, celgene, dermavant, dermira, ds biopharma, galderma, glaxosmithkline, incyte, janssen, leo pharma, lilly, medimmune, novartis, pfizer, regeneron, roche, sanofi genzyme, sun pharma, and ucb. michael cork has served as a clinical trial investigator for astellas, galapagos, johnson & johnson, leo pharma, la roche-posay, msd, novartis, perrigo, regeneron, sanofi genzyme, and stiefel; has served as an advisory board member, consultant, and/or invited lecturer for pfizer inc., amgen, astellas, bayer, johnson & johnson, leo pharma, l’oréal, msd, novartis, regeneron, sanofi genzyme, stiefel, and unilever; has received honoraria from astellas, johnson & johnson, leo pharma, novartis, regeneron, sanofi genzyme, and stiefel; and has received research funding from bayer. luís puig has received consultancy/speaker’s honoraria from and/or participated in clinical trials sponsored by abbvie, almirall, amgen, baxalta, biogen, boehringer ingelheim, celgene, gebro, janssen, jsc biocad, leo-pharma, lilly, merck-serono, msd, mylan, novartis, pfizer, regeneron, roche, sandoz, samsung-bioepis, sanofi and ucb. petra arlert, azra kurbasic, and lise soldbro are employees of leo pharma a/s. eric l. simpson is a consultant and investigator for regeneron/sanofi, dermira, menlo pharmaceuticals, lilly, abbvie, genentech, medimmune, gsk, leo pharma, celgene, and pfizer. acknowledgements the ecztra 6 clinical trial was sponsored by leo pharma a/s (ballerup, denmark). this poster is an encore of a previous presentation at the 12th international symposium on atopic dermatitis, 17 – 19 october 2022. editorial support from alphabet health (new york, ny, usa) by juliel espinosa, phd and meredith whitaker, phd was funded by leo pharma (usa). affect of ad on cdlqi domains: weeks 0-16 • at week 16, ad had ‘not at all’: • affected how embarrassed or self-conscious the patient was over the past 7 days in 49.0/47.9% of tralokinumab (150/300 mg) treated patients vs 37.0% receiving placebo (figure 2a) • affected friendships over the past 7 days in 82.3/80.2% of tralokinumab (150/300 mg) treated patients vs 71.7% receiving placebo (figure 2b) • influenced clothes you wear over the past 7 days in 55.2/55.2% of tralokinumab (150/300 mg) treated patients vs 43.5% receiving placebo (figure 2c) • affected going out, play, or hobbies over the past 7 days in 54.2/59.4% of tralokinumab (150/300 mg) treated patients vs 43.5% receiving placebo (figure 2d) • at week 16, 60.4/61.5% of tralokinumab (150/300 mg) treated patients had ‘not at all’ avoided swimming or other sports due to ad over the past 7 days vs 51.1% receiving placebo (figure 2e) • at week 16, ad had ‘not at all’: • affected school/holiday over the past 7 days in 44.8/49.0% of tralokinumab (150/300 mg) treated patients vs 28.3% receiving placebo (figure 2f) • impacted trouble with other people over the past 7 days in 83.3/82.3% of tralokinumab (150/300 mg) treated patients vs 78.3% receiving placebo (figure 2g) • at week 16, problem with treatment affected patients ‘not at all’ over the past 7 days in 50.0/59.4% of tralokinumab (150/300 mg) treated patients vs 39.1% receiving placebo (figure 2h) 0 5 10 15 20 25 30 35 40 45 0 2 4 6 8 10 12 14 16 31.0 39.5 15.9tralokinumab 150 mg q2w (n=84) placebo (n=82) tralokinumab 300 mg q2w (n=81) r e sp o n d e rs ( % ) week cdlqi reduction ≥6b -8 -6 -4 -2 0 0 2 4 6 8 10 12 14 16 –6.1 –6.7 –4.1 tralokinumab 150 mg q2w (n=95) placebo (n=89) tralokinumab 300 mg q2w (n=94) a d ju st e d m e a n c h a n g e in c d l q i cdlqia8 * * * * ** * *** *** * week a b adata collected after permanent discontinuation of tralokinumab or initiation of rescue medication after week 2 were not included. repeated measurements model: change = treatment*week+baseline*week+region+baseline iga. in case of no post-baseline assessments, the week 2 change was imputed as 0. bpatients who received rescue medication after week 2 were considered non-responders, as were patients with missing data at week 16. *mantel-haenszel risk difference compared with placebo, stratified by region and baseline iga *p<0.05 vs placebo; **p<0.01 vs placebo; ***p<0.001 vs placebo. patients with at least baseline data available were included in the cdlqi adjusted mean change analysis (a), and patients with cdlqi ≥6 at baseline were included in the cdlqi reduction ≥6 analysis (b). cdlqi, children's dermatology life quality index; iga, investigator’s global assessment; q2w, every 2 weeks. figure 1. (a) adjusted mean change in cdlqi and (b) reduction of cdlqi ≥6 by week materials and methods study design • adolescents with moderate-to-severe ad (n=289) received tralokinumab 150 mg or 300 mg or placebo every 2 weeks (q2w) during the initial phase (weeks 0–16) • qol and impact on school was measured using the cdlqi, a 10-item questionnaire assessing patient/caregiver-reported ad impact • this analysis presents the results for most of the cdlqi subdomains (excluding ‘how itchy, sore, painful’ and ‘affected sleep’, which are addressed by other analyses elsewhere) • change and proportion of patients with ≥6-point reduction (minimal important difference) from baseline to week 16 in total cdlqi were evaluated using a linear mixed model for repeated measures and cochranmantel-haenszel test, respectively • individual cdlqi domains were evaluated with the pearson chi-square test • rescue medication [topical calcineurin inhibitor (tci), tcs, systemic treatment] was used if medically necessary (i.e., to control intolerable ad symptoms) objective • to examine the impact of tralokinumab on ad-related qol and school in adolescents during weeks 0–16 of the ecztra 6 trial (nct03526861) results change in cdlqi and reduction of cdlqi ≥6: weeks 0-16 • at week 16, adjusted mean change from baseline in cdlqi was significantly greater with tralokinumab 150 mg (–6.1) and 300 mg (–6.7) vs placebo (–4.1); difference* –2.0 (p=0.04) and –2.6 (p=0.007) respectively (figure 1a) • more patients had ≥6-point reduction (minimal important difference in adolescents) with tralokinumab 150 mg (31.0%) and 300 mg (39.5%) vs placebo (15.9%); difference* 14.1% (p=0.029) and 23.9% (p<0.001), respectively (figure 1b) introduction • tralokinumab is a fully human monoclonal antibody that binds with high affinity to interleukin-13, a key driver of atopic dermatitis (ad) pathogenesis1–3 • ad is a chronic inflammatory skin disease associated with poor quality of life (qol) and a substantial psychosocial impact in adolescents4,5 • ad is associated with poor school behaviours in adolescent patients, including poor task completion, poor connectedness and impulsivity6 • the phase 3 ecztra 6 trial (nct03526861) of patients aged 12–17 years with moderate-to-severe ad showed: • tralokinumab monotherapy had superior efficacy to placebo for all primary and key secondary efficacy endpoints, including change in children’s dermatology life quality index (cdlqi) from baseline to week 167 • here we present a detailed analysis of cdlqi results from ecztra 6 introduction scan to download a copy of this poster copies of this poster and its content, obtained through this qr code, are for personal use only and may not be reproduced without written permission from the authors figure 2. affect of ad on cdlqi domains (weeks 0-16) last observation carried forward (locf) was used for patients who used rescue medication or discontinued treatment (observation prior to rescue initiation/treatment discontinuation) or had missing data. sensitivity analyses used observed data, and locf was used for patients missing data. rescue medication was used by 56.4%, 33.7% and 29.9% in the placebo, tralokinumab 150 mg and 300 mg arms, respectively. across arms, >70% of patients used topical corticosteroids only. p values = pearson chi-square test vs placebo a b c d how embarrassed, self conscious affected friendships influenced clothes you wear affected going out, play, hobbies avoided swimming or other sports problems at school or holiday trouble with other people how much a problem is treatment e f g h slide 1: the impact of tralokinumab on quality of life and school in patients aged 12–17 with atopic dermatitis: results from the phase 3 ecztra 6 trial powerpoint presentation presented at the winter clinical dermatology conference hawaii® (wch23), january 13–18, 2023, kohala coast, hi, usa conclusions • once-daily, nonsteroidal roflumilast foam 0.3% provided improvement across multiple efficacy endpoints versus vehicle in patients with sd in a phase 3 trial – 80% of patients achieved iga success and >50% achieved complete clearance by week 8 – >60% of patients achieved an itch response at week 8, with significant improvements at the 2and 4-week assessments • local tolerability was highly favorable as reported by patient and investigator assessments of irritation, burning, and stinging, consistent with safety profiles in prior trials table 1. baseline demographics and disease characteristics roflumilast foam 0.3% (n=304) vehicle (n=153) age in years, mean (std dev) 43.2 (16.8) 41.8 (17.5) sex male, n (%) 153 (50.3) 75 (49.0) female, n (%) 151 (49.7) 78 (51.0) race, n (%) american indian or alaska native 4 (1.3) 0 asian 18 (5.9) 10 (6.5) black or african american 36 (11.8) 15 (9.8) native hawaiian or other pacific islander 0 1 (0.7) white 234 (77.0) 122 (79.7) more than 1 race 1 (0.3) 1 (0.7) other 11 (3.6) 4 (2.6) ethnicity, n (%) hispanic or latino 69 (22.7) 28 (18.3) not hispanic or latino 235 (77.3) 125 (81.7) iga score, n (%) 3 (moderate) 287 (94.4) 141 (92.2) 4 (severe) 17 (5.6) 12 (7.8) erythema score, n (%) 2 (mild) 0 1 (0.7) 3 (moderate) 282 (92.8) 141 (92.2) 4 (severe) 22 (7.2) 11 (7.2) scaling score, n (%) 2 (mild) 0 0 3 (moderate) 256 (84.2) 130 (85.0) 4 (severe) 48 (15.8) 23 (15.0) wi-nrs, mean score (std dev) 5.06 (2.34) 4.74 (2.29) wi-nrs score ≥4, n (%) 206 (67.8) 98 (64.1) bsa, mean % (std dev) 2.89 (2.03) 2.98 (2.57) scalp, n (%) 291 (95.7) 136 (88.9) face, n (%) 186 (61.2) 98 (64.1) eyelids involved, n (%) 29 (9.5) 13 (8.5) ears, n (%) 146 (48.0) 79 (51.6) neck, n (%) 33 (10.9) 13 (8.5) trunk, n (%) 28 (9.2) 18 (11.8) other, n (%) 11 (3.6) 4 (2.6) bsa: body surface area; iga: investigator global assessment; std dev: standard deviation; wi-nrs: worst itch numeric rating scale. figure 2. iga success (0 or 1 with a 2-grade improvement) iga success = clear or almost clear with at least a 2-grade improvement from baseline intent-to-treat population; missing scores imputed using multiple imputations. error bars represent 95% confidence interval. statistical significance was concluded at the 1% significance level (2-sided). iga: investigator global assessment. references 1. dessinioti c, katsambas a. clin dermatol. 2013;31:343–351. 2. dong c, et al. j pharmacol exp ther. 2016;358:413–422. 3. zirwas m, et al. 30th congress of the european academy of dermatology and venereology (eadv) virtual, september 29–october 2, 2021. introduction • seborrheic dermatitis (sd) is a common, chronic inflammatory skin disease that affects patients of all ages, with a global prevalence of approximately 5%1 • treatment is via topical therapies, including antifungal agents and corticosteroids, which have limitations (side effects and/or inability to use on both hair-/non–hairbearing areas) • roflumilast is a selective phosphodiesterase 4 (pde4) inhibitor with greater affinity for pde4 than apremilast and crisaborole (25to >300-fold more potent in in vitro assays)2 • topical roflumilast is being investigated as a once-daily, nonsteroidal treatment for long-term management of psoriasis (fda-approved july 29, 2022), atopic dermatitis, and sd • efficacy, safety, and tolerability of roflumilast foam have been demonstrated in a phase 2a trial in sd3 and a subsequent open-label safety trial (nct04091646/nct04445987) • here, we report the results of a phase 3 trial (nct04973228) of roflumilast foam 0.3% in patients with sd methods • this phase 3 randomized, parallel-group, double-blind, vehicle-controlled trial was conducted in patients ≥9 years old with at least moderate sd affecting scalp and/or non-scalp areas (figure 1) • the primary efficacy endpoint was investigator global assessment (iga) success (iga of clear or almost clear plus ≥2-grade improvement from baseline) at week 8 results • baseline patient demographics and disease characteristics were similar between the groups (table 1) • overall, significantly more roflumilast-treated patients than vehicle-treated patients achieved the primary efficacy endpoint of iga success (figure 2) and iga status of clear (figure 3) at week 8 – percentages of patients achieving iga success and iga clear at weeks 2 and 4 were also greater with roflumilast • significantly greater percentages of roflumilastthan vehicle-treated patients achieved secondary endpoints of: – wi-nrs success at weeks 2, 4, and 8 (figure 4) – overall assessment of erythema score of 0 (figure 5) at week 8 – overall assessment of scaling score of 0 (figure 5) at week 8 • local tolerability was favorable on investigatorand patient-rated assessments (figure 6) • overall incidence of treatment-emergent adverse events (teaes), serious adverse events, and teaes leading to discontinuation were low, with similar rates between roflumilast and vehicle (table 2) andrew blauvelt,1 javier alonso-llamazares,2 neal bhatia,3 zoe d. draelos,4 janet dubois,5 seth b. forman,6 melinda gooderham,7 scott t. guenthner,8 adelaide a. hebert,9 edward lain,10 angela y. moore,11 kim a. papp,12 linda stein gold,13 matthew zirwas,14 saori kato,15 scott snyder,15 david krupa,15 patrick burnett,15 david r. berk,15 david h. chu15 1oregon medical research center, portland, or, usa; 2driven research llc, coral gables, fl, usa; 3therapeutics clinical research, san diego, ca, usa; 4dermatology consulting services, high point, nc, usa; 5dermresearch, inc., austin, tx, usa; 6forcare medical center, tampa, fl, usa; 7skin centre for dermatology, probity medical research and queen’s university, peterborough, on, canada; 8the dermatology center of indiana, pc, and the indiana clinical trials center, pc, plainfield, in, usa; 9ut health mcgovern medical school, houston, tx, usa; 10sanova dermatology, austin, tx, usa; 11arlington research center, arlington, tx, and baylor university medical center, dallas, tx, usa; 12probity medical research and k papp clinical research, waterloo, on, canada; 13henry ford medical center, detroit, mi, usa; 14dermatologists of the central states, probity medical research, and ohio university, bexley, oh, usa; 15arcutis biotherapeutics, inc., westlake village, ca, usa efficacy and safety of roflumilast foam 0.3% in patients with seborrheic dermatitis in a phase 3 trial figure 1. study design aas this study is a single pivotal trial, the statistical significance of the primary endpoint was assessed at the 1% significance level (2-sided). to control for multiple testing, the 1% alpha was partitioned to 0.0033 for wi-nrs endpoints and 0.0067 for other secondary endpoints. bsa: body surface area; iga: investigator global assessment; qd: once daily; w: week; wi-nrs: worst itch numeric rating scale. endpointsa • primary – iga success (0 or 1 with a 2-grade improvement) at w8 • secondary: – iga success at w2 and w4 – iga of clear at w8 – wi-nrs at w2, w4, and w8 – erythema score of 0 at w8 – scaling score of 0 at w8 • safety & tolerability eligibility • diagnosis of at least moderate seborrheic dermatitis (iga >3) • age ≥9 years • ≤20% bsa roflumilast foam 0.3% qd (n=304) vehicle qd (n=153) r a n d o m iz e 2:1 n=457 8 weeks dosing figure 3. iga status of clear (0) iga clear = iga score of 0. intent-to-treat population; missing scores imputed using multiple imputations, p-values are not adjusted for multiple testing. error bars represent 95% confidence interval. iga: investigator global assessment. figure 4. wi-nrs success missing scores imputed using multiple imputations. error bars represent 95% confidence interval. wi-nrs success = ≥4-point improvement in patients with baseline wi-nrs score ≥4; evaluated at α=0.0033. figure 5. erythema and scaling scores of 0 intent-to-treat population; missing scores imputed using multiple imputations. error bars represent 95% confidence interval. evaluated at α=0.0067. table 2. adverse events n (%) roflumilast foam 0.3% (n=304) vehicle (n=153) patients with any teae 70 (23.0) 33 (21.6) patients with any treatment-related teae 8 (2.6) 5 (3.3) patients with any treatment-emergent saea 1 (0.3) 0 patients who discontinued study due to aeb 2 (0.7) 3 (2.0) most common teae (>1% in any group), preferred termc covid-19 11 (3.6) 5 (3.3) urinary tract infection 4 (1.3) 3 (2.0) nausea 5 (1.6) 0 nasopharyngitis 4 (1.3) 1 (0.7) application-site pain 1 (0.3) 3 (2.0) sinusitis 0 2 (1.3) akeratoacanthoma, not in application site, deemed unrelated. breasons for discontinuation in the roflumilast-treated group includes diarrhea/hematochezia/abdominal pain in one patient with a past history of crohn’s and decreased potassium in the second patient. cpresented in descending order for overall rates. ae: adverse event; sae: serious adverse event; teae: treatment-emergent adverse event. figure 6. local tolerability assessments (safety population) ascale for investigator-rated local tolerability: 0 = no evidence of irritation; 1 = minimal erythema, barely perceptible; 2 = definite erythema, readily visible; minimal edema or minimal papular response; 3 = erythema and papules; 4 = definite edema; 5 = erythema, edema and papules; 6 = vesicular eruption; 7 = strong reaction spreading beyond application site. bscale for patient-rated local tolerability: 0 = no sensation; 1 = slight warm, tingling sensation; not really bothersome; 2 = definite warm, tingling sensation that is somewhat bothersome; 3 = hot, tingling/stinging sensation that has caused definite discomfort. week 2 week 4 week 8 p e rc e n ta g e o f p a ti e n ts roflumilast foam 0.3% vehicle p<0.0001 p=0.0002 p<0.0001 week 2 week 4 week 8 p e rc e n ta g e o f p a ti e n ts roflumilast foam 0.3% vehicle p<0.0001 p=0.001 p<0.0001 week 2 week 4 week 8 p e rc e n ta g e o f p a ti e n ts roflumilast foam 0.3% vehicle p<0.0001 p=0.0053 p<0.0001 week 2 week 4 week 8 p e rc e n ta g e o f p a ti e n ts roflumilast foam 0.3% vehicle p<0.0001 p=0.0003 p<0.0001 acknowledgements • this study was supported by arcutis biotherapeutics, inc. • thank you to the investigators and their staff for their participation in the trial. • we are grateful to the study participants and their families for their time and commitment. • writing support was provided by christina mcmanus, phd, alligent biopharm consulting llc, and funded by arcutis biotherapeutics, inc. 100% 98.9% 100%100% 100% 100% baseline week 4 week 8 p a ti e n ts ( % ) 92.4% 96.1% 97.8%92.8% 92.7% 94.8% baseline week 4 week 8 p a ti e n ts ( % ) roflumilast foam 0.3% (n=304) vehicle foam (n=153) n=296 n=151 n=277 n=140 n=264 n=136 ~80% of patients achieved iga success at week 8 >50% of patients achieved iga of clear week 2 week 4 week 8 p e rc e n ta g e o f p a ti e n ts roflumilast foam 0.3% (n=206) vehicle (n=98) p=0.0001 p=0.0016 p=0.0007 100 80 60 40 20 0 100 80 60 40 20 0 >60% of patients achieved wi-nrs 4-pt response 100 80 60 40 20 0 >50% of patients achieved erythema=0 (none) 100 80 60 40 20 0 >50% of patients achieved scaling=0 (none) 100 80 60 40 20 0 patient-rated local tolerability: % patients with no or mild sensation investigator-rated local tolerability: % patients with no signs of irritation 100 80 60 40 20 0 100 80 60 40 20 0 n=304 n=152 n=238 n=137 n=277 n=134 disclosures ab, ja-l, nb, ab, zdd, jd, sbf, mg, stg, aah, el, aym, kap, lsg, and mz are investigators and/or consultants for arcutis biotherapeutics, inc. and received grants/research funding and/or honoraria; sk, dk, pb, dhc, and drb are employees of arcutis biotherapeutics, inc. additional disclosures provided on request. slide 1: efficacy and safety of roflumilast foam 0.3% in patients with seborrheic dermatitis in a phase 3 trial matching-adjusted indirect comparison (maic) of deucravacitinib versus adalimumab for the treatment of patients with moderate to severe plaque psoriasis over 2 years april w. armstrong,1 sang hee park,2 vardhaman patel,2 malcolm hogan,3 wei-jhih wang,4 david davidson,2 viktor chirikov4 1keck school of medicine, university of southern california, los angeles, ca, usa; 2bristol myers squibb, princeton, nj, usa; 3bristol myers squibb, toronto, canada; 4open health evidence & access, bethesda, md, usa presented at the winter clinical dermatology conference hawaii®, january 13-18, 2023, kohala coast, hi, and winter clinical miami™, february 17-20, 2023, miami, fl email for april w. armstrong, md, mph: aprilarmstrong@med.usc.edu this poster may not be reproduced without written permission from the authors. synopsis • deucravacitinib is an oral, selective, allosteric tyrosine kinase 2 (tyk2) inhibitor that has demonstrated superior efficacy compared with apremilast and placebo in 2 phase 3 randomized controlled trials,1,2 and is approved by the us food and drug administration for the treatment of adults with moderate-tosevere plaque psoriasis (pso) who are candidates for systemic therapy or phototherapy • a previous systemic literature review and network analysis indirectly compared the efficacy of deucravacitinib with other systemic nonbiologic and biologic treatments3 — at week 52, psoriasis area and severity index (pasi) response rates for deucravacitinib were comparable to those of the most effective first-generation biologics, including adalimumab • a matching-adjusted indirect comparison (maic) evaluated the results of the adalimumab reveal trial vs those of the deucravacitinib poetyk pso-1 and pso-2 trials to extend the comparison beyond 52 weeks • among patients with moderate to severe pso who switched from placebo to continuous treatment after week 16, this maic suggests that patients receiving deucravacitinib had a higher long-term response rate than those receiving adalimumab — response rates of at least 75% reduction from baseline in pasi scores (pasi 75) were significantly higher with deucravacitinib vs adalimumab at week 112 and were numerically higher at week 52 — response rates of at least 90% reduction from baseline in pasi scores (pasi 90) were similar between the 2 treatments at week 52, but were numerically higher for deucravacitinib vs adalimumab at week 112 background • poetyk pso-1 and pso-2 — randomized, double-blind, placebo-controlled studies assessing the efficacy and safety of deucravacitinib vs placebo and apremilast in adults with moderate to severe pso — at week 16, patients randomized to placebo crossed over to deucravacitinib — patients completing pso-1 and pso-2 could enroll in a long-term, open-label extension during which patients received deucravacitinib 6 mg once daily • a previous indirect comparison assessed the clinical efficacy associated with deucravacitinib and other selected active biologic and nonbiologic treatments3 — the pasi 75 response rates were within the range of those for first-generation biologics at weeks 10-16 and 24-28 — at week 52, the pasi 75 response rate for deucravacitinib was comparable to that of adalimumab and ustekinumab objective • primary objective — compare the rates of pasi 75 response at week 112 in patients with pso treated with deucravacitinib vs adalimumab, adjusting for differences in baseline characteristics by using maic • secondary objective — compare the rates of pasi 75 and pasi 90 response at week 52 as well as the rate of pasi 90 response at week 112, using maic, for patients treated with deucravacitinib vs adalimumab methods • a literature search was conducted to identify long-term extension (lte) trials that were similar to the design of the poetyk pso-lte and reported similar outcomes of interest (ie, pasi 75 and pasi 90 over the long term) adalimumab trial selection: reveal extension trial (nct00195676) • randomized, double-blind, placebo-controlled study (figure 1a) examining the clinical efficacy of adalimumab in patients with moderate to severe pso • patients who did not achieve a pasi 75 response at week 16 entered an open-label extension study of adalimumab — the long-term extension included the specific population of interest (patients with moderate to severe pso), with a study design in which patients received continuous adalimumab over a long-term period • only patients initially randomized to placebo then switched to adalimumab at week 16 were included in the maic • only published aggregate data were available4 deucravacitinib trial selection: poetyk pso-lte (nct04036435) • randomized, double-blind, placeboand active-controlled phase 3 study with individual patient-level data available • in both poetyk trials, patients with moderate to severe pso were randomized to placebo and switched to deucravacitinib at week 16 in an open-label, long-term extension (figure 1b) • only patients initially randomized to placebo then switched to deucravacitinib were included in the maic, given the outcomes reported figure 1. study design comparison between (a) reveal and (b) poetyk pso-1 and pso-2 a. b. screening ≤ 28 days period a initial response 16-week dbpc period b sustained response 17-week open label period c loss of adequate response 19-week dbpc adalimumab 40 mg eow† (n = 26) adalimumab 40 mg eow (n = 22) adalimumab 40 mg eow (n = 580) adalimumab 40 mg eow* (n = 812) placebo eow (n = 398) 1 :1 r an d o m iz at io n ≥ pasi 75 response continue to period c patients with < pasi 75 response enter ole patients with pasi responses > 50 and < 75 enter ole n = 1212 ≥ pasi 75 response continue to period b 2:1 randomization week 0 16 33 52 adalimumab 40 mg eow (n = 250) placebo eow (n = 240) 165100 160 100cumulative exposure (weeks) 16 24 520 primary endpoint 56 60 68 76 88 112 124 1364 8 12 20 28 32 36 40 44 48 480 964 8 16 24 36 60 72 84exposure relative to lte (weeks) 1 year 188 deucravacitinib 6 mg qdplacebo (n = 166) deucravacitinib 6 mg qd apremilast 30 mg bid titrate* deucravacitinib 6 mg qd (n = 332) apremilast 30 mg bid (n = 168) b li n d e d s w it ch t o o p e n -l ab e l d e u cr av ac it in ib poetyk pso-1 and pso-2 poetyk pso-lte deucravacitinib 6 mg qdplacebo (n = 255) deucravacitinib 6 mg qd (n = 511) deucravacitinib 6 mg qd< pasi 75 deucravacitinib 6 mg qd< pasi 75 deucravacitinib 6 mg qd deucravacitinib 6 mg qd placebo apremilast 30 mg bid (n = 254) ≥ pasi 75 1:1 2 years po et y k p so -2 1: 2: 1 ra nd om iz at io n po et y k p so -1 1: 2: 1 ra nd om iz at io n open-label deucravacitinib 6 mg qd (n = 298) 148 240 < pasi 50 ≥ pasi 50 deucravacitinib 6 mg qdplacebo ≥ pasi 75 ole: adalimumab 40 mg eow‡ *data reported through the 120-day lte cutoff date of october 1, 2021. †after 80 mg at week 16 and 40 mg at week 17. ‡only patients who received placebo from baseline and started adalimumab at week 16 (n = 345) were included in the present study. bid, twice daily; dbpc, double-blind placebo-controlled; eow, every other week; lte, long-term extension; ole, open-label extension; pasi 50, ≥ 50% reduction from baseline in psoriasis area and severity index; pasi 75, ≥ 75% reduction from baseline in pasi; qd, once daily. analyses • base case: age, sex, race, weight, duration of pso, body surface area (bsa), baseline pasi score, previous use of phototherapy/systemic nonbiologics/ systemic biologics, and week 16 pasi 75/week 16 pasi 90 scores • sensitivity analysis 1: history of psoriatic arthritis and physician global assessment score, in addition to base case variables • sensitivity analysis 2: previous use of phototherapy/systemic nonbiologics/systemic biologics removed to only match on disease severity, demographics, and other baseline characteristics • sensitivity analysis 3: previous use of phototherapy/systemic nonbiologics/systemic biologics were limited to the prior 12 months only, to align with the definition used in reveal • sensitivity analysis 4: same as base case, with weight truncation allowed • truncation was conducted in sensitivity analyses if any extreme weights were observed outcome measures • primary outcome: pasi 75 response rate at week 112 • secondary outcomes: pasi 75 response rate at week 52; pasi 90 response rate at weeks 52 and 112 • outcomes were analyzed using last observation carried forward (locf) to be consistent with the reported methods for reveal results • baseline characteristics — before matching, patients in the poetyk studies were generally older, had higher mean baseline pasi scores, and were more likely to have been treated previously with systemic nonbiologic and biologic treatments compared with the patients in reveal (tables 1, 2) table 1. demographics and baseline characteristics before and after matching: base case parameter reveal (n = 345) poetyk prematch (n = 329) poetyk postmatch (n = 147)a age, mean (sd), years 45.3 (13.2) 47.6 (14.1) 45.3 (13.9) male, % 67.0 70.2 67.0 white, % 91.3 85.4 91.3 weight, mean (sd), kg 94.9 (22.6) 89.9 (20.5) 94.9 (22.4) duration of pso, mean (sd), years 18.6 (11.8) 18.7 (13.0) 18.6 (16.6) history of psoriatic arthritis, % 27.8 15.8 14.4 bsa, mean (sd) 25.5 (14.6) 25 (15.4) 25.5 (16.4) pasi score, mean (sd) 18.8 (7.1) 20.6 (8.0) 18.8 (6.7) pga, % moderate 55.7 83.3 87.3 severe 44.3 16.7 12.7 previous pso treatment, % phototherapy 13.6 38.9 13.6 systemic nonbiologic 20.0 44.7 20.0 systemic biologic 13.9 29.5 13.9 week 16 pasi 75 response, % 7.0 13.4 7.0 week 16 pasi 90 response, % 2.0 4.3 2.0 aeffective sample size after reweighting. bsa, body surface area; pasi, psoriasis area and severity index; pga, physician’s global assessment; pso, psoriasis; sd, standard deviation. table 2. demographics and baseline characteristics: sensitivity analyses parameter reveal (n = 345) sensitivity analysis 1a (n = 86) sensitivity analysis 2 (n = 238) sensitivity analysis 3 (n = 221) sensitivity analysis 4 (n = 150) age,b mean (sd), years 45.3 (13.2) 45.1 (12.3) 45.3 (13.9) 45.3 (13.8) 45.4 (13.9) male, % 67.0 65.2 67.0 67.0 67.4 white,b % 91.3 90.8 91.3 91.3 91.2 weight,b mean (sd), kg 94.9 (22.6) 94.6 (21.3) 94.9 (21.9) 94.9 (22.1) 94.7 (22.4) duration of pso, mean (sd), years 18.6 (11.8) 19.0 (14.3) 18.6 (13.0) 18.6 (12.8) 18.6 (13.7) history of psoriatic arthritis, % 27.8 29.4 14.3 13.9 14.5 bsa, mean (sd) 25.5 (14.6) 25.0 (15.1) 25.5 (16.3) 25.5 (16.1) 25.5 (16.4) pasi,b mean (sd) 18.8 (7.1) 18.8 (6.6) 18.8 (6.5) 18.8 (6.5) 18.8 (6.8) pga,b % moderate 55.7 58.9 87.8 88.6 87.2 severe 44.3 41.1 12.2 11.4 12.8 previous pso treatment, % phototherapyb 13.6 14.4 39.6 13.6 13.7 systemic nonbiologicb 20.0 21.1 44.7 20.0 20.1 systemic biologicb 13.9 14.7 29.3 13.9 14.0 week 16 pasi 75b response, % 7.0 7.4 7.0 7.0 7.0 week 16 pasi 90b response, % 2.0 2.1 2.0 2.0 2.0 aresults were truncated at 1% and 99% owing to extreme weights. bp < 0.05 for prematch comparisons between poetyk pso-1 and 2 and reveal, using t tests for continuous variables and chi-square tests for categorical variables. bsa, body surface area; pasi, psoriasis area and severity index; pga, physician’s global assessment; pso, psoriasis; sd, standard deviation. • before matching — pasi 75 response rates were higher for deucravacitinib than adalimumab at weeks 52 (69.9% vs 64.0%) and 112 (71.7% vs 54.0%) — similarly, pasi 90 response rates were higher for deucravacitinib than adalimumab at week 52 (42.9% vs 40.0%) and week 112 (46.8% vs 34.0%) • after matching — pasi 75 response rate was significantly higher for deucravacitinib at week 112 compared with adalimumab (figure 2), with a mean difference of 13.2% (95% confidence interval [ci], 4.0–22.5) — deucravacitinib had numerically higher pasi 75 response rates at week 52 and pasi 90 response rates at week 112 compared with adalimumab, and pasi 90 response rates were comparable at week 52 (figure 3) • similar results were seen in the sensitivity analyses — pasi 75 response rates were significantly higher for deucravacitinib than adalimumab at week 112 (figure 4) — pasi 90 response rates were numerically higher at week 112 for deucravacitinib vs adalimumab (figure 5) — at week 52, pasi 75 and pasi 90 response rates were comparable for deucravacitinib and adalimumab figure 2. base case: adjusted pasi 75 response rates at weeks 52 and 112 reveal poetyk 64.0 54.0 68.1 67.2 0 10 20 30 40 50 60 70 80 p a si 7 5 r e sp o n se r at e , % mean difference 4.1 (95% ci -4.9, 13.1) mean difference 13.2 (95% ci 4.0, 22.5) 52 64 76 88 100 112 week pasi 75, ≥ 75% reduction from baseline in psoriasis area and severity index (pasi) scores. figure 3. base case: adjusted pasi 90 response rates at weeks 52 and 112 reveal poetyk 52 64 76 88 100 112 week p a si 9 0 r e sp o n se r at e , % 39.4 34.0 40.0 41.3 0 5 10 15 20 25 30 35 40 45 50 mean difference 7.3 (95% ci -2.0, 16.7) mean difference -0.6 (95% ci -10.0, 8.9) pasi 90, ≥ 90% reduction from baseline in psoriasis area and severity index (pasi) scores. figure 4. sensitivity analyses: adjusted pasi 75 response rates at weeks 52 and 112 base case sensitivity analysis 4 sensitivity analysis 3 sensitivity analysis 2 sensitivity analysis 1 4.1 (-4.9, 13.1) 3.9 (-5.0, 12.9) 2.7 (-5.4, 10.8) 2.6 (-5.3, 10.4) 0.4 (-11.2, 12.1) base case sensitivity analysis 4 sensitivity analysis 3 sensitivity analysis 2 sensitivity analysis 1 13.2 (4.0, 22.5) 13.1 (3.9, 22.4) 13.3 (5.1, 21.5) 13.5 (5.5, 21.5) 11.8 (0.1, 23.5) mean difference (95% ci) -20 week 52 week 112 -10 0 10 20 30 greater efficacy of deucravacitiniblower efficacy of deucravacitinib sensitivity analysis 1: history of psoriatic arthritis and physician global assessment scores plus base case variables. sensitivity analysis 2: matched only on pasi and baseline demographics (previous psoriasis treatment removed). sensitivity analysis 3: previous use of phototherapy/systemic nonbiologics/systemic biologics in the prior 12 months. sensitivity analysis 4: base case with extreme weights truncated. pasi 75, ≥ 75% reduction from baseline in psoriasis area and severity index (pasi) scores. figure 5. sensitivity analyses: adjusted pasi 90 response rates at weeks 52 and 112 -0.6 (-10.0, 8.9) -0.8 (-10.2, 8.5) -4.4 (-12.4, 3.7) -3.1 (-11.1, 4.9) -0.7 (-12.0, 10.6) 7.3 (-2.0, 16.7) 7.6 (-1.8, 16.9) 6.9 (-1.3, 15.0) 6.9 (-1.1, 14.9) 2.8 (-8.0, 13.6) -20 -10 0 10 20 30 mean difference (95% ci) greater efficacy of deucravacitiniblower efficacy of deucravacitinib base case sensitivity analysis 4 sensitivity analysis 3 sensitivity analysis 2 sensitivity analysis 1 base case sensitivity analysis 4 sensitivity analysis 3 sensitivity analysis 2 sensitivity analysis 1 week 52 week 112 sensitivity analysis 1: history of psoriatic arthritis and physician global assessment scores plus base case variables. sensitivity analysis 2: matched only on pasi and baseline demographics (previous psoriasis treatment removed). sensitivity analysis 3: previous use of phototherapy/systemic nonbiologics/systemic biologics in the prior 12 months. sensitivity analysis 4: base case with extreme weights truncated. pasi 90, ≥ 90% reduction from baseline in psoriasis area and severity index (pasi) scores. conclusions • among patients with moderate to severe pso who switched from placebo to continuous deucravacitinib treatment after week 16, this maic suggests that patients who receive deucravacitinib have a greater long-term response rate than those who receive adalimumab — pasi 75 response rates were significantly higher with deucravacitinib vs adalimumab at week 112 and were numerically higher at week 52 — pasi 90 response rates were comparable between the 2 treatments at week 52, but were numerically higher for deucravacitinib at week 112 compared with adalimumab — the sensitivity analyses showed similar results, with pasi 75 and 90 response rates with deucravacitinib being consistently higher than those for adalimumab at week 112 • limitations — methodologies differed between the studies; differences in inclusion criteria and analyses may have affected these comparisons — adjustments to published adalimumab data were based on aggregate proportions of patient characteristics and did not necessarily control for the joint distribution between characteristics associated with each individual patient — associations between outcomes and baseline factors at the study level may be different than they would have been on the patient level, introducing potential uncertainty • these results highlight the therapeutic role of deucravacitinib in pso references 1. armstrong aw, et al. j am acad dermatol. 2022; july 9 [online ahead of print]. 2. strober b, et al. j am acad dermatol. 2022; september 14 [online ahead of print]. 3. armstrong a, et al. [poster] presented at fall clinical dermatology conference, october 20–23, 2022, las vegas, nv. 4. gordon k, et al. j am acad dermatol. 2012;66:241-251. acknowledgments • this study was sponsored by bristol myers squibb • medical writing and editorial assistance was provided by cheryl jones of peloton advantage, llc, an open health company, and funded by bristol myers squibb disclosures • awa: research grants and personal fees: bristol myers squibb, eli lilly, janssen, leo pharma, and novartis; personal fees: boehringer ingelheim/parexel, celgene, dermavant, genentech, glaxosmithkline, menlo therapeutics, merck, modernizing medicine, ortho dermatologics, pfizer, regeneron, sanofi genzyme, science 37, sun pharma, and valeant; grants: dermira, kyowa hakko kirin, and ucb, outside the submitted work • shp, vp, mh, dd: employees of and may own stock options in bristol myers squibb • w-jw and vc: employees of open health evidence & access, which received funding from bristol myers squibb characteristic spesolimab (n=35) placebo (n=18) age, years, mean (sd) 43.2 (12.1) 42.6 (8.4) female, n (%) 21 (60.0) 15 (83.3) race, n (%) asian 16 (45.7) 13 (72.2) white 19 (54.3) 5 (27.8) bmi, kg/m2, mean (sd) 27 (8) 26 (10) il36rn mutation positive*, n (%) 8 (22.9) 6 (33.3) gppga total score, n (%) 3 (moderate) 28 (80.0) 15 (83.3) 4 (severe) 7 (20.0) 3 (16.7) gppga pustulation subscore, n (%) 2 (mild) 6 (17.1) 5 (27.8) 3 (moderate) 16 (45.7) 7 (38.9) 4 (severe) 13 (37.1) 6 (33.3) pain vas, median (iqr) 79.8 (70.5–87.8) 70.0 (50.0–89.4) jda gpp severity index, n (%) mild 9 (25.7) 5 (27.8) moderate 19 (54.3) 8 (44.4) severe 4 (11.4) 4 (22.2) missing 3 (8.6) 1 (5.6) mean, sd 7.9 (3.0) 8.4 (2.8) median, (min, max) 8.0 (2, 14) 8.0 (4, 14) medication for gpp prior to randomization, n (%)† 18 (51.4) 9 (50.0) clobetasol propionate 5 (14.3) 1 (5.6) acitretin 4 (11.4) 1 (5.6) cyclosporin 2 (5.7) 3 (16.7) betamethasone valerate 2 (5.7) 2 (11.1) methotrexate 1 (2.9) 3 (16.7) betamethasone dipropionate 1 (2.9) 2 (11.1) betamethasone; calcipotriol 2 (5.7) 1 (5.6) emulsifying wax; paraffin, liquid, white soft paraffin 1 (2.9) 2 (11.1) subgroup (n/n)* response rate, risk difference % of patients (95% ci) overall (19/35 vs 1/18) 54.3 vs 5.6 0.487 (0.215–0.672) baseline gppga total score 3 (16/28 vs 1/15) 57.1 vs 6.7 0.505 (0.163–0.706) 4 (3/7 vs 0/3) 42.9 vs 0.0 0.429 (−0.343–0.816) presence of plaque psoriasis at baseline no (15/29 vs 1/15) 51.7 vs 6.7 0.451 (0.117–0.659) yes (4/6 vs 0/3) 66.7 vs 0.0 0.667 (−0.109–0.957) baseline gppga pustulation subscore <4 (12/22 vs 1/12) 54.5 vs 8.3 0.462 (0.089–0.697) =4 (7/13 vs 0/6) 53.8 vs 0.0 0.538 (0.070–0.808) baseline jda gpp severity index mild or moderate (13/28 vs 1/13) 0.387 (0.038–0.614) severe (4/4 vs 0/4) 100.0 vs 0.0 1.000 (0.261–1.000) background medication before randomization no (14/20 vs 1/10) 70.0 vs 10.0 0.600 (0.177–0.823) yes (5/15 vs 0/8) 33.3 vs 0.0 0.333 (−0.069–0.616) sex female (11/21 vs 1/15) 52.4 vs 6.7 0.457 (0.151–0.693) male (8/14 vs 0/3) 57.1 vs 0.0 0.571 (−0.191–0.823) race asian (10/16 vs 1/13) 62.5 vs 7.7 0.548 (0.173–0.798) white (9/19 vs 0/5) 47.4 vs 0.0 0.474 (−0.073–0.716) bmi <25 kg/m2 (9/15 vs 0/9) 60.0 vs 0.0 0.600 (0.204–0.837) 25 to <30 kg/m2 (5/10 vs 1/6) 50.0 vs 16.7 0.333 (−0.231–0.713) ≥30 kg/m2 (5/10 vs 0/3) 50.0 vs 0.0 0.500 (−0.215–0.826) il36rn mutation positive† no (9/21 vs 0/11) 42.9 vs 0.0 0.429 (0.081–0.660) yes (7/8 vs 1/6) 87.5 vs 16.7 0.708 (0.126–0.960) favors placebo favors single-dose iv spesolimab 900 mg −0.50 −0.25 0.00 0.25 0.50 0.75 1.00 1.25 46.4 vs 7.7 subgroup (n/n)* response rate, risk difference % of patients (95% ci) overall (15/35 vs 2/18) 42.9 vs 11.1 0.317 (0.022–0.527) baseline gppga total score 3 (13/28 vs 2/15) 46.4 vs 13.3 0.331 (0.000–0.564) 4 (2/7 vs 0/3) 28.6 vs 0.0 0.286 (−0.418–0.710) presence of plaque psoriasis at baseline no (12/29 vs 2/15) 41.4 vs 13.3 0.280 (−0.044–0.513) yes (3/6 vs 0/3) 50.0 vs 0.0 0.500 (−0.283–0.902) baseline gppga pustulation subscore <4 (9/22 vs 1/12) 40.9 vs 8.3 0.326 (−0.025–0.574) =4 (6/13 vs 1/6) 46.2 vs 16.7 0.295 (−0.206–0.649) baseline jda gpp severity index mild or moderate (9/28 vs 2/13) 32.1 vs 15.4 0.168 (−0.160–0.416) severe (4/4 vs 0/4) 100.0 vs 0.0 1.000 (0.261–1.000) background medication before randomization no (12/20 vs 2/10) 60.0 vs 20.0 0.400 (−0.019–0.685) yes (3/15 vs 0/8) 20.0 vs 0.0 0.200 (−0.176–0.481) sex female (10/21 vs 2/15) 47.6 vs 13.3 0.343 (0.026–0.604) male (5/14 vs 0/3) 35.7 vs 0.0 0.357 (−0.352–0.665) race asian (8/16 vs 2/13) 50.0 vs 15.4 0.346 (−0.031–0.647) white (7/19 vs 0/5) 36.8 vs 0.0 0.368 (−0.178–0.619) bmi <25 kg/m2 (8/15 vs 0/9) 53.3 vs 0.0 0.533 (0.118–0.787) 25 to <30 kg/m2 (3/10 vs 2/6) 30.0 vs 33.3 −0.033 (−0.532–0.430) ≥30 kg/m2 (4/10 vs 0/3) 40.0 vs 0.0 0.400 (−0.313–0.755) il36rn mutation positive† no (6/21 vs 1/11) 28.6 vs 9.1 0.195 (–0.151–0.454) yes (6/8 vs 1/6) 75.0 vs 16.7 0.583 (0.018–0.902) favors placebo favors single-dose iv spesolimab 900 mg −0.50 −0.25 0.00 0.25 0.50 0.75 1.00 1.25 purpose to investigate the consistency of the spesolimab treatment effect by conducting a subgroup analysis of the primary and key secondary endpoints from the effisayil 1 study, according to patient demographics and clinical characteristics at baseline. baseline demographics and clinical characteristics the placebo arm included a higher proportion of female and asian patients than the spesolimab arm; clinical characteristics were generally balanced between study arms subgroup analysis of gppga total score of 0 or 1 at week 1 the efficacy of spesolimab (gppga pustulation subscore of 0 or 1) was consistent across patient subgroups missing values or any use of other medication for gpp within the first week of the trial were regarded as non-response for the analysis of these endpoints. *single-dose iv spesolimab 900 mg vs placebo; subgroup analysis by age was not performed as only 2 patients were aged ≥65 years; †patients who were homozygous or heterozygous for an il36rn mutation were considered positive. efficacy of spesolimab for the treatment of gpp flares across prespecified patient subgroups in the effisayil 1 study a. david burden1, yukari okubo2, min zheng3, diamant thaçi4, peter van de kerkhof5, na hu6, christian thoma7, siew eng choon8 1institute of infection, immunity and inflammation, university of glasgow, glasgow, uk; 2department of dermatology, tokyo medical university, tokyo, japan; 3department of dermatology, second affiliated hospital, zhejiang university, school of medicine, hangzhou, zhejiang, china; 4universitat zu luebeck, lubeck, germany; 5department of dermatology, radboud university, nijmegen, the netherlands; 6boehringer ingelheim (china) investment co., ltd, shanghai, china; 7boehringer ingelheim international gmbh, biberach, germany; 8department of dermatology, hospital sultanah aminah, clinical school johor bahru, monash university malaysia, subang jaya, malaysia introduction • gpp is a rare and potentially life-threatening autoimmune disease characterized by recurrent flares of widespread sterile pustules, with or without systemic inflammation1,2 • effisayil 1 (nct03782792) was a multicenter, randomized, double-blind, placebo-controlled study of spesolimab, an anti-il-36 receptor antibody, in patients presenting with a gpp flare. within 1 week of a single dose of spesolimab, rapid pustular and skin clearance was observed compared with placebo3 − primary endpoint (gppga pustulation subscore of 0; no visible pustules): 54% vs 6% (one-sided p<0.001) − key secondary endpoint (gppga total score of 0 or 1; clear or almost clear skin): 43% vs 11% (one-sided p=0.0118) conclusions • estimates of spesolimab treatment effect in each patient subgroup were generally similar to those of the overall population for both the primary and key secondary endpoints • the efficacy of spesolimab (pustular and skin clearance) compared with placebo was consistent across all prescribed subgroups • however, it should be noted that several subgroups had very few patients • these data provide further evidence supporting the use of spesolimab to treat all patients presenting with a gpp flare methods • the efficacy of spesolimab was evaluated in prescribed patient subgroups from effisayil 1, if at least 2 categories of the subgroup included ≥5 patients: sex, age, race, bmi, gppga pustulation subscore at baseline, gppga total score at baseline, jda gpp severity score at baseline, presence of plaque psoriasis at baseline, and il36rn status • scan the qr code at the bottom of this poster to see full details of the effisayil 1 study design3,4 results subgroup analysis from the effisayil 1 study showed that the efficacy of spesolimab (pustular and skin lesion clearance) was consistent across all prespecified patient populations, including those with or without il36rn mutations genotyping data were available for 46 patients. dna sequencing was not performed in 7 patients. *patients who were homozygous or heterozygous for an il36rn mutation were considered positive. †background medication for gpp in at least 3 patients of the overall population. forest plot of risk difference for gppga total score of 0 or 1 at week 1 subgroup analysis of gppga pustulation subscore of 0 at week 1 missing values or any use of other medication for gpp within the first week of the trial regarded as non-response for the analysis of these endpoints. *single-dose iv spesolimab 900 mg vs placebo; subgroup analysis by age was not performed as only 2 patients were aged ≥65 years. †patients who were homozygous or heterozygous for an il36rn mutation were considered positive. forest plot of risk difference for gppga pustulation subscore of 0 at week 1 the efficacy of spesolimab (gppga pustulation subscore of 0) was consistent across patient subgroups abbreviations bmi, body mass index; ci, confidence interval; fda, u.s. food and drug administration; gpp, generalized pustular psoriasis; gppga, generalized pustular psoriasis physician global assessment; il-36, interleukin-36; iqr, interquartile range; iv, intravenous; jda, japanese dermatological association; sd, standard deviation; pain vas, pain visual analog scale. references 1. navarini aa, et al. j eur acad dermatol venereol 2017;31:1792–1799; 2. fujita h, et al. j dermatol 2018;45:1235–1270; 3. bachelez h, et al. n engl j med 2021;385:2431–2440; 4. choon se, et al. bmj open 2021;11:e043666. disclosures & acknowledgments the study was supported and funded by boehringer ingelheim. adb declares paid consulting activities for abbvie, almirall, boehringer ingelheim, celgene, eli lilly, janssen, leo pharma, novartis, and ucb. yo declares grants or contracts from eisai, maruho pharmaceutical, and shiseido torii; and consulting fees from abbvie, amgen, boehringer ingelheim, bristol myers squibb, celgene, eisai, eli lilly, janssen, jimro, kyowa kirin, leo pharma, maruho pharmaceutical, novartis, pfizer, sanofi, sun pharmaceutical industries, taiho pharmaceutical, tanabe-mitsubishi, torii pharmaceutical, and ucb. mz declares receiving grants, consulting fees, and/or speaker’s fees from abbvie, boehringer ingelheim, janssen-cilag, leo pharma china, novartis, pfizer, and xian-janssen. dt declares having attended advisory boards and/or received consultancy fees and/or receiving grants as an investigator from abbvie, almirall, amgen, beiersdorf, bristol meyers squibb, boehringer ingelheim, ds-pharma, eli lilly, galapagos, glaxosmithkline, janssen-cilag, leo pharma, maruho, medac, morphosys, norvartis, pfizer, regeneron pharmacueticals, inc., samsung, sandoz, sanofi, sun pharmaceutical industries, and ucb. pvdk received fees for consultancy service or lectureships from almirall, abbvie, boehringer ingelheim, bristol myers squibb, dermavant sciences, eli lilly, janssen, leo pharma, novartis, and ucb. nh and ct are employees of boehringer ingelheim. sec declares paid activities as an advisor, speaker, or consultant for abbvie, boehringer ingelheim, eli lilly, janssen, leo pharma, msd, novartis, pfizer, sanofi, and ucb. the authors met criteria for authorship as recommended by the international committee of medical journal editors (icmje). the authors did not receive payment related to the department of the poster. boehringer ingelheim was given the opportunity to review the poster for medical and scientific accuracy, as well as intellectual property considerations. geetha vilventhraraja of open health communications (london, uk) provided writing, editorial, and formatting support, which was contracted and funded by boehringer ingelheim. scan the qr code for an interactive, electronic devicefriendly copy of the original presentation from aad 2022 https://bit.ly/3qgwhdc click the icon to access an interactive microsite, containing the original presentation from aad 2022 presented at winter clinical dermatology conference hawaii® (january 13–18, 2023; kohala coast, hi, usa) and winter clinical miami™ (february 17–20, 2023; miami, fl, usa) previously presented at the 80th american academy of dermatology (aad) annual meeting (march 25–29, 2022; boston, ma, usa) presented at winter clinical dermatology conference 2020 | hawaii | jan 17–22 2020 previously presented at 28th eadv congress 2019 durability of response in patients with psoriatic arthritis treated with certolizumab pegol over 216 weeks: post-hoc analyses from the rapid-psa study a. b. gottlieb,1 p. gisondi,2 j. eells,3 l. peterson,4 a. kavanaugh5 1department of dermatology, icahn school of medicine at mount sinai, new york, ny; 2university of verona, verona, italy; 3ucb pharma, slough, uk; 4ucb pharma, raleigh, nc; 5university of california, san diego, ca references 1. certolizumab pegol prescribing information. available at www.fda.gov/drugs; 2. certolizumab pegol summary of product characteristics. available at www.ema.europa.eu/ema; 3. van der heijde d. rmd open 2018;4:e000582; 4. van der heijde d. eular 2018; 5. gordon k. eadv 2019;870; 6. gordon k. eadv 2019;1556; 7. gordon k. aad 2019; 8. coates lc. ann rheum dis 2010;69:48–53. author contributions substantial contributions to study conception/design, or acquisition/ analysis/interpretation of data: abg, pg, je, lp, ak; drafting of the publication, or revising it critically for important intellectual content: abg, pg, je, lp, ak; final approval of the publication: abg, pg, je, lp, ak. author disclosures abg: research/educational grants: allergan, eli lilly, incyte, janssen, leo pharma and novartis. current consulting/advisory board agreements/speakers bureau: abbvie, allergan, beiersdorf inc., bristol-myers squibb, celgene corp., dermira, eli lilly, incyte, janssen inc, novartis, reddy labs, sienna, sun pharmaceutical industries, ucb pharma, valeant; pg: consultant for abbvie, abiogen, almirall, celgene, eli lilly, janssen, leo pharma, merck, msd, novartis, otsuka, pfizer, pierre fabre, sanofi, ucb pharma; je, lp: employees of ucb pharma; ak: research grants from abbott, amgen, bristol-myers squibb, janssen, pfizer, roche, and ucb pharma. acknowledgements the study was funded by ucb pharma. we thank the patients and their caregivers in addition to the investigators and their teams who contributed to this study. the authors acknowledge bartosz łukowski, msc, ucb pharma, brussels, belgium for publication coordination and ruth le fevre, phd, costello medical, cambridge, uk for medical writing and editorial assistance. all costs associated with development of this poster were funded by ucb pharma. objective • to assess the durability of response in patients with psoriatic arthritis who were treated with certolizumab pegol over 216 weeks. background • certolizumab pegol (czp) is a unique, fc-free, pegylated anti-tumour necrosis factor (tnf) that is approved by the fda and ema for the treatment of psoriatic arthritis (psa).1,2 • in the 4-year, phase 3 rapid-psa trial (nct01087788), substantial proportions of czp-treated patients achieved targets such as minimal disease activity (mda) and very low disease activity (vlda), consistent with other biologics, including anti-tnfs.3,4 • in phase 3 trials in plaque psoriasis (pso), czp-treated patients showed clinical improvements, which were sustained over three years of treatment.5 • responder rates observed at weeks 16 and 48 were durable over time.6,7 • here, we assess the durability of the initial clinical response to czp in patients with psa. methods study design • rapid-psa was a 4-year, phase 3 trial, double-blind and placebo-controlled to week 24, dose-blind to week 48 and open-label to week 216. • patients with psa were randomised 1:1:1 to czp 200 mg every two weeks (q2w), czp 400 mg every four weeks (q4w) or placebo; – all patients randomised to czp received czp 400 mg loading dose at weeks 0, 2 and 4, and continued their assigned dose during the open-label period to week 216 (figure 1). patients • included patients were aged ≥18 years with a diagnosis of active psa of ≥6 months’ duration, and had failed treatment with ≥1 disease-modifying anti-rheumatic drug (dmard). conclusions • of patients with psa who initially responded to czp treatment and achieved an mda response at week 24 and completed treatment to week 216, >85% maintained this clinical response after four years of treatment. • even at the more stringent vlda threshold, >80% of week 24 responders who completed to week 216 maintained their response to four years. • these findings highlight the long-term durability of the clinical response to czp in patients with moderate to severe psa, with substantial proportions of patients reaching and maintaining stringent treatment targets. bmi: body mass index; bsa: body surface area; crp: c-reactive protein; czp: certolizumab pegol; dmard: disease modifying anti-rheumatic drug; hla-b27: human leukocyte antigen b27; sd: standard deviation; tnf: tumour necrosis factor. table 1. patient baseline characteristics figure 2. durability of response through weeks 24–216 data are observed case. data are pooled for patients treated with czp 200 mg q2w and czp 400 mg q4w. amda plus bsa ≤3% responses are reported in patients who had bsa ≥3% at baseline. bsa: body surface area; czp: certolizumab pegol; mda: minimal disease activity; q2w: every two weeks; q4w: every four weeks; vlda: very low disease activity. • patients with prior exposure to >2 biologic agents (>1 anti-tnf) for the treatment of psa or pso were excluded. • in this analysis, data were pooled for patients randomised to czp 200 mg q2w and czp 400 mg q4w. study assessments and statistical analyses • psa severity was assessed using seven mda criteria (see summary box). figure 1. rapid-psa study design czp: certolizumab pegol; ld: loading dose; psa: psoriatic arthritis; q2w: every two weeks; q4w: every four weeks. • week 24–216 data are reported for patients who were randomised to czp at week 0 and who achieved: – week 24 mda (≥5/7 mda criteria) – week 24 vlda (7/7 mda criteria) – baseline psoriatic bsa ≥3% and week 24 bsa ≤3% plus ≥4/6 of the remaining mda criteria (mda plus bsa ≤3%) • data are shown for patients randomised to czp at week 0 as observed case. results patient disposition • 273 patients were randomised to czp 200 mg q2w (n=138) or czp 400 mg q4w (n=135) at week 0 (figure 1). • patient baseline characteristics are shown in table 1. week 24 response • of the patients randomised to czp, at week 24: – 95/273 (34.8%) patients achieved mda – 37/273 (13.6%) achieved vlda • at baseline 166/273 patients had bsa ≥3%, 39 (23.5%) of whom achieved mda plus bsa ≤3% at week 24. • there was no clear trend observed in the components that contributed to failure to achieve vlda response. durability of response • responder rates for all three composite outcome measures remained high to week 216 in patients who demonstrated a week 24 response and completed week 216 (figure 2). • numerically, the greatest durability to week 216 was seen for mda (figure 2). n (%) unless otherwise stated all czp (n=273) age, years, mean (sd) 47.7 (11.6) male 126 (46.2) bmi, kg/m2, mean (sd) 30.0 (6.4) crp, mean (sd) 14.3 (22.3) hla-b27 positivity 41 (15.0) psoriasis bsa ≥3% 166 (60.8) nail psoriasis 197 (72.2) enthesitis 172 (63.0) dactylitis 94 (34.4) suspected axial involvement 213 (78.0) prior use of synthetic dmards 1 165 (60.4) ≥2 103 (37.7) prior anti-tnf exposure 54 (19.8) week 48 96 156 168 180 192 204 216 mda, % (n/n) 85.1 (80/94) 88.9 (80/90) 90.7 (78/86) 89.4 (76/85) 87.8 (72/82) 87.7 (71/81) 92.3 (72/78) 86.8 (66/76) week 48 96 156 168 180 192 204 216 vlda, % (n/n) 71.4 (25/35) 88.2 (30/34) 77.4 (24/31) 70.0 (21/30) 66.7 (20/30) 82.8 (24/29) 82.1 (23/28) 81.5 (22/27) week 48 96 156 168 180 192 204 216 mda plus bsa ≤3% (n/n) 73.7 (28/38) 82.9 (29/35) 81.8 (27/33) 71.9 (23/32) 80.0 (24/30) 72.4 (21/29) 78.6 (22/28) 82.8 (24/29) summary we assessed durability of the initial clinical response to certolizumab pegol (czp) in patients with psoriatic arthritis (psa) psa activity and severity were measured using seven criteria: tender joint count ≤1 swollen joint count ≤1 psoriasis area and severity index ≤1 or ≤3% body surface area a�ected patient pain visual analogue score ≤15 patient global disease activity visual analogue score ≤20 health assessment questionnaire disability index ≤0.5 tender entheseal points ≤1 proportions of patients at week 216 who maintained their clinical response from week 24: mda: 87% vlda: 82% minimal disease activity (mda) ≥5/7 mda criteria8 very low disease activity (vlda) =7/7 mda criteria8 week: 0 16 24 48 216 screening double-blind open-labeldose-blind ld 400 mg weeks 0, 2, 4 czp 200 mg q2w czp 400 mg q4w czp 200 mg q2w czp 400 mg q4w czp 200 mg q2w czp 400 mg q4w ld ld placebo ld 400 mg weeks 16, 18, 20 ld 400 mg weeks 24, 26, 28 adult patients with active psa n=409 placebo escape: patients who failed to achieve a 10% decrease in tender joint count and swollen joint count at both week 14 and week 16 were randomised in a blinded manner to escape treatment from week 16. placebo completers: patients who completed the double-blind phase were randomised to czp in a dose-blind manner. n=138 n=135 n=136 n=30 n=29 n=30 n=31 ld ld ld ld p ro p o rt io n o f p a ti e n ts ( % ) 82.9 (n=29/35) 82.8 (n=24/29) 80 0 16814412096724824 216 week 60 40 100 20 192 80 0 16814412096724824 216 week p ro p o rt io n o f p a ti e n ts ( % ) 60 40 100 20 192 86.8 (n=66/76) 88.9 (n=80/90) p ro p o rt io n o f p a ti e n ts ( % ) 88.2 (n=30/34) 81.5 (n=22/27) 80 0 16814412096724824 216 week 60 40 100 20 192 a) week 24 mda responders (n=95) b) week 24 vlda responders (n=37) c) week 24 mda plus bsa ≤3% responders (n=39) in patients with baseline bsa ≥3%a one-year pharmacovigilance update of brodalumab mark lebwohl,1 craig leonardi,2 jashin j. wu,3 paul yamauchi,4 nicole rawnsley,5 mohammed merchant,6 binu alexander,6 abby jacobson5 1icahn school of medicine at mount sinai, new york, ny; 2saint louis university school of medicine, st louis, mo; 3dermatology research and education foundation, irvine, ca; 4dermatology institute & skin care center, santa monica, ca; 5ortho dermatologics (a division of bausch health us, llc), bridgewater, nj; 6bausch health us, llc, bridgewater, nj 2020 winter clinical dermatology conference hawaii® • january 17-22, 2020 • kohala coast, hi synopsis • efficacy and safety of brodalumab, a fully human anti–interleukin-17 receptor a monoclonal antibody, have been demonstrated in one phase 2 and three phase 3 trials (amagine-1/-2/-3)1-3 • there are limited data on the effects of brodalumab treatment in a real-world setting objective • to report an update of brodalumab 1-year pharmacovigilance in the united states (august 15, 2017–august 14, 2018) methods • observational data were collected for us patients who received brodalumab (n=826) and reported an adverse event (ae) through routine pharmacovigilance reporting from healthcare providers and patients • aes were categorized by medical dictionary for regulatory activities preferred term and system organ class, seriousness, and (company-determined) causality • brodalumab exposure was estimated by first shipment date to last dose date plus 55 days (ie, 5 half-lives of brodalumab) • aes were summarized with descriptive statistics and as exposure-adjusted rates per patient-year (py) • the analysis was performed on january 11, 2019, for all reports between august 15, 2017, and august 14, 2018 results most commonly reported aes • the most commonly reported aes were psoriasis flare, drug ineffectiveness, arthralgia, depression, diarrhea, and pain (table 1) – of 9 patients reporting diarrhea, 4 were taking other medications that could potentially cause gastrointestinal upset – of 9 patients reporting pain, 4 had a history of joint or muscle pain and 4 experienced pain <4 weeks after brodalumab initiation – among 11 patients reporting depression, 4 discontinued brodalumab and 2 had a history of depression (mental health history was not provided in 6 reports); no events of depression were serious aes of interest • there were no reports of completed suicides or suicide attempts, major adverse cardiac events, new-onset ulcerative colitis, or new-onset crohn disease • there were 3 reports of malignancy (hepatic, lung, and ovarian; 0.01 events per py), all considered unrelated to brodalumab (figure 1) • there were 4 reports of serious infections (0.02 events per py; figure 1) possibly related to brodalumab, with 2 reports in the same patient • there were 2 events of fungal infection (0.01 events per py; figure 1) but no reports of serious fungal infection – 1 nonserious event of oral fungal candida infection was reported in which brodalumab was discontinued and symptoms resolved – a nonserious event of vulvovaginal mycotic candida infection was reported in which brodalumab was maintained and symptoms resolved acknowledgments: this study was sponsored by ortho dermatologics. medical writing support was provided by medthink scicom and funded by ortho dermatologics. ortho dermatologics is a division of bausch health us, llc. references: 1. siliq [package insert]. bridgewater, nj: bausch health us, llc; 2017. 2. lebwohl et al. n engl j med. 2015;373:1318-1328. 3. papp et al. br j dermatol. 2016;175:273-286. conclusions • one-year pharmacovigilance reporting for brodalumab revealed that the most commonly reported ae was psoriasis flare • few patients receiving brodalumab reported depression, and none reported serious fungal infections, suicide attempts, or completed suicides © 2020. all rights reserved. table 1. summary of most common adverse events reported in the us pharmacovigilance monitoring of brodalumab (august 15, 2017–august 14, 2018) 0.02 0.01 0.01 0 0 0 0 0.01 0.02 0.03 0.04 0.05 serious infection fungal infection malignancy ex po su re -a dj us te d ev en t ra te pe r pa ti en tye ar suicide crohn disease mace figure 1. exposure-adjusted adverse events of interest per patient-year. exposure-adjusted event rate per patient-year = number of events/216 patient-years of exposure. mace, major adverse cardiac event. ae event, n (r) estimated weeks of brodalumab treatment, mean (min-max)a event related to brodalumab, n discontinuation, n psoriasis flare 26 (0.12) 10.8 (1.7-30.1) 2 2 drug ineffectiveness 18 (0.08) 15.5 (1.7-52.1) 1 2 arthralgia 16 (0.07) 4.1 (0.4-10.0) 1 4 depression 11 (0.05) 14.9 (1.0-35.3) 0 4 diarrhea 9 (0.04) 6.5 (0.4-12.9) 0 2 pain 9 (0.04) 5.7 (0.1-12.9) 0 5 psoriasis flare included the meddra categories of “psoriasis,” “condition aggravated,” and “ill-defined disorder.” drug ineffectiveness included the meddra categories of “drug ineffective” and “drug ineffective for unapproved indication.” depression included the meddra categories of “depression,” “depressive symptoms,” and “depressed mood.” pain included the meddra categories of “pain” and “pain in extremity.” aduration (weeks) of brodalumab treatment was estimated by calculating the number of days from the reported start of brodalumab treatment to the reported end of treatment. patients whose start or end date was unknown were excluded from the calculation. ae, adverse event; max, maximum duration; meddra, medical dictionary for regulatory activities; min, minimum duration; r, exposure-adjusted rate per patient-year. acknowledgements: medical writing support was provided by prescott medical communications group (chicago, il) with financial support from ortho dermatologics | presented at the fall clinical dermatology conference • october 17-20, 2019 • las vegas, nv synopsis ◾ psoriasis is an immune-mediated disease that is often chronic with frequent remissions and exacerbations1,2 ◾ topical corticosteroids are the mainstay of treatment, though long-term safety remains a concern, limiting use3,4 ◾ adherence to topical therapy by patients with psoriasis is also generally poor, but may improve with simple regimens and once-daily therapy5,6 ◾ a topical treatment for psoriasis that provides maintenance of efficacy after stopping treatment may be beneficial for patients, though data on maintenance of efficacy posttreatment are sparse objective ◾ to investigate the maintenance of effect posttreatment following once-daily application of halobetasol propionate 0.01%/tazarotene 0.045% (hp/taz) lotion in patients with moderateto-severe psoriasis methods ◾ this was a 1-year multicenter, open-label study (nct02462083) in patients ≥18 years of age with moderate-to-severe plaque psoriasis • an investigator’s global assessment (iga) score of 3 or 4 (5-point scale; 0=clear and 4=severe) and body surface area (bsa) of 3-12% were needed to enroll in the study ◾ participants were treated with hp/taz lotion once-daily for 8 weeks and intermittently as needed in 4-week intervals (figure 1) • at week 8, treatment was stopped for participants that achieved treatment success, defined as iga score of 0 or 1 (‘clear’ or ‘almost clear’); participants who did not reach treatment success were treated for 4 additional weeks • all participants were re-evaluated at week 12 • those demonstrating ≥1-grade improvement from baseline iga continued the study and were subsequently managed in 4-week cycles (eg, treated with hp/taz lotion once-daily if they had not achieved treatment success or receiving no treatment until the next evaluation if they had achieved treatment success) long-term management of moderate-to-severe plaque psoriasis: maintenance of treatment success following cessation of fixed combination halobetasol propionate 0.01% and tazarotene 0.045% (hp/taz) lotion figure 2. time to first treatment successa with hp/taz (n=318) 2 weeks 12.6% 4 weeks 24.8% 8 weeks 17.0% 12 weeks 15.4% 16 weeks 10.1% 20 weeks 5.3% 24 weeks 13.8% 28 weeks 0.3% 32 weeks 0.6% atreatment success defined as score of 0 or 1 on iga; blue sections show treatment success achieved within the first 8 weeks. hp/taz, halobetasol propionate 0.01%/tazarotene 0.045%; iga, investigator’s global assessment. figure 3. time to retreatment with hp/taz (n=226a) 6.6% did not relapse (no retreatment) 55.3% no retreatment for ~1 month 28.3% no retreatment for ~2 months 19.5% no retreatment for ~3 months 29-56 days (n=61) 0-28 days (n=101) 57-84 days (n=20) 85-112 days (n=16) ≥113 days (n=13) no relapse (n=15) aparticipants still enrolled post 8 weeks in the study and who stopped therapy after achieving treatment success (defined as a score of 0 or 1 on iga). hp/taz, halobetasol propionate 0.01%/tazarotene 0.045%; iga, investigator’s global assessment. ◾ for individuals participating for at least 1 year, 77.5% maintained a bsa level of ≤5% and 49.3% maintained a bsa level of ≤3% during the study (figure 4) figure 4. maintained body surface area (bsa) from week 8 to end of study with hp/taz ≤5% bsa ≤3% bsa 49.3% 77.5% 39.7% 71.5% 0% 20% 40% 60% 80% 100% subjects participating for at least 6 months (n=390) subjects participating for at least 1 year (n=138) p e rc e n ta g e o f p a rt ic ip a n ts hp/taz, halobetasol propionate 0.01%/tazarotene 0.045%. conclusions ◾ a novel lotion formulation of halobetasol propionate 0.01%/tazarotene 0.045% (hp/taz) demonstrated rapid and sustained treatment success in participants with moderate-to-severe psoriasis when followed for 1 year, with more than half of participants not requiring retreatment for at least one month ◾ these data are consistent with those reported in an earlier study of hp/taz lotion, where 55% of participants who were treatment successes remained so at the end of the 4-week posttreatment follow-up references 1. nestle fo, et al. n engl j med. 2009;361(5):496-509. 2. cohen sn, et al. clin exp dermatol. 2012;37 suppl 1:13-8. 3. kim wb, et al. can fam physician. 2017;63(4):278-285. 4. uva l, et al. int j endocrinol. 2012;2012:561018. 5. svendsen, mt, et al. j dermatolog treat. 2019:1-10. 6. belinchón i, et al. patient prefer adherence. 2016;10:2357-2367. author disclosures dr. linda stein gold is an investigator/consultant or speaker for ortho dermatologics, leo, dermavant, incyte, novartis, abbvie, and lilly. dr. mark lebwohl is an employee of mount sinai and receives research funds from: abbvie, amgen, arcutis, astrazeneca, boehringer ingelheim, celgene, clinuvel, eli lilly, incyte, janssen research & development, llc, kadmon corp., llc, leo pharmaceuticals, medimmune, novartis, ortho dermatologics, pfizer, sciderm, ucb, inc., and vidac. dr. lebwohl is also a consultant for allergan, almirall, arcutis, inc., avotres therapeutics, birchbiomed inc., boehringer-ingelheim, bristol-myers squibb, cara therapeutics, castle biosciences, corrona, dermavant sciences, foundation for research and education in dermatology, inozyme pharma, leo pharma, meiji seika pharma, menlo, mitsubishi, neuroderm, pfizer, promius/dr. reddy’s laboratories, theravance, and verrica. dr. neal bhatia has received honoraria from ferndale laboratories, inc., promius pharma, llc, novartis, allergan, biofrontera ag, intraderm pharmaceuticals, almirall, sun pharmaceutical industries, la roche-posay, mayne pharma group, ortho dermatologics, pierre fabre dermo-cosmétique us, isdin, galderma laboratories, skinfix, inc., and grants/research funding from aclaris therapeutics, inc., asana biosciences, llc, crown laboratories, inc., leo pharma us, dusa pharmaceuticals, inc., menlo therapeutics, par pharmaceutical, pfizer inc., perrigo company, realm therapeutics, sienna biopharmaceuticals, sol-gel technologies, soligenix, inc., strata skin sciences, vidac pharma, brickell biotech, inc., dermira, glenmark generics inc., sanofi/regeneron, actavis, biopharmx, foamix, cutanea life sciences, mc2 therapeutics, ucb, abbvie, atacama therapeutics, naked biome inc., kiniksa pharmaceuticals, ltd., bms, dr. reddy, and vypome (pending). dr. lin is an employee of ortho dermatologics. dr. pillai is an employee of bausch health americas. ◾ maximum continuous exposure was 24 weeks; at week 24, if continuous treatment was received, participants needed an iga score of 0 or 1 to continue in the study ◾ in this study, cerave® hydrating cleanser and cerave® moisturizing lotion (l’oreal, ny) were provided as needed for optimal moisturization/cleaning of the skin figure 1. open-label study design screening successa treatment stopped for 4 weeks no success continued once-daily hp/taz for 4 weeks improvementb continued study and managed in 4-week cycles for up to 1 year, with patients re-evaluated every 4 weeks for treatment successa no improvement discontinued from study oncedaily hp/taz 1 yearweek 24 if continuous treatment was received, iga score of 0 or 1 needed to continue study day 0 week 12 evaluated for ≥1-grade improvement from baseline iga week 8 evaluated for treatment successa maximum continuous exposure was 24 weeks. atreatment success defined as score of 0 or 1 on iga. bimprovement defined as ≥1-grade improvement from baseline iga. hp/taz, halobetasol propionate 0.01%/tazarotene 0.045%; iga, investigator’s global assessment. results ◾ a total of 555 participants were treated with hp/taz; 550 had post-baseline safety data ◾ mean age was 51.9 years, 65.6% were male, and 86.0% were white; mean bsa at baseline was 5.6% ◾ overall, 318 participants (57.8%) achieved treatment success at some point during the study; the majority (54.4%, n=173) achieved treatment success within the first 8 weeks (figure 2; blue sections) ◾ in many participants, treatment success was rapid, being achieved within the first 2 and 4 weeks in 12.6% and 37.4% of those who achieved treatment success, respectively (figure 2) ◾ of 226 participants who stopped therapy after achieving treatment success, 55.3% did not require retreatment for at least 29 days and 6.6% did not require any retreatment (figure 3) linda stein gold, md1; mark g lebwohl, md2; neal bhatia, md3; tina lin, pharmd4; radhakrishnan pillai, phd5 1henry ford hospital, detroit, mi; 2icahn school of medicine at mount sinai, new york, ny; 3therapeutics clinical research, san diego, ca; 4ortho dermatologics, bridgewater, nj; 5bausch health americas, inc, petaluma, ca long-term efficacy and safety of brodalumab in patients with psoriasis whose disease did not respond to prior biologics mark lebwohl,1 lawrence green,2 miriam bettencourt,3 scott fretzin,4 abby jacobson5 1icahn school of medicine at mount sinai, new york, ny; 2george washington university school of medicine, washington, dc; 3university of nevada, las vegas, nv; 4 dawes fretzin dermatology group, indianapolis, in; 5ortho dermatologics (a division of bausch health us, llc), bridgewater, nj 39th annual fall clinical dermatology conference® for dermatologists • october 17-20, 2019 • las vegas, nv introduction • patients with psoriasis who experience treatment failure to, or whose disease does not respond to, biologic therapies over time may encounter medical or economic consequences, including higher mean total healthcare-related costs and increased use of other medications1 • brodalumab is a fully human anti–interleukin-17 receptor a monoclonal antibody that is efficacious in treating moderateto-severe psoriasis2 • it is crucial to understand the efficacy of subsequent biologic treatment in individuals whose disease did not respond to initial biologic treatment objectives • to assess long-term efficacy and safety of brodalumab in 2 multi center randomized clinical trials (amagine-2/-3; clinicaltrials.gov identifiers: nct01708603, nct01708629) in patients with moderate-to-severe plaque psoriasis whose disease did not respond to 1, 2, or ≥3 prior biologics3 methods • in amagine-2/-3, patients were initially randomized to brodalumab 140 or 210 mg every 2 weeks, ustekinumab, or placebo during a 12-week induction phase (figure 1) – at week 12, patients who received brodalumab were re-randomized to either the same or a different brodalumab regimen, patients receiving ustekinumab continued on ustekinumab, and patients receiving placebo were switched to brodalumab 210 mg every 2 weeks • at week 52, all patients entered the long-term extension phase and received brodalumab • 408 patients from amagine-2/-3 who received any dose of brodalumab through week 120 were included in this post-hoc analysis, which comprised – 160 patients with a lack of response to 1 biologic – 112 patients with a lack of response to 2 biologics – 136 patients with a lack of response to ≥3 biologics • skin clearance was monitored by psoriasis area and severity index 75% improvement (pasi 75), pasi 90, and pasi 100 responses • safety was summarized by exposure-adjusted treatmentemergent adverse event (teae) rates results efficacy • among patients whose disease did not respond to 1, 2, or ≥3 prior biologics, skin clearance rates were comparable from weeks 52 to 120 in those achieving pasi 75 (figure 2a), pasi 90 (figure 2b), and pasi 100 (figure 2c) • in an observed analysis at week 52, pasi 75 response rates in patients whose disease did not respond to 1, 2, or ≥3 prior biologics were 86.4%, 87.2%, and 85.3%, respectively – pasi 90 response rates were 71.2%, 75.6%, and 72.5%, respectively – pasi 100 response rates were 42.4%, 50.0%, and 41.2%, respectively • at week 120, observed pasi 75 response rates were 82.1%, 84.3%, and 93.2% in patients whose disease did not respond to 1, 2, or ≥3 prior biologics, respectively – pasi 90 response rates were 64.1%, 74.5%, and 79.7%, respectively – pasi 100 response rates were 50.0%, 54.9%, and 54.2%, respectively safety • across all years, exposure-adjusted teae rates per 100 patientyears in patients receiving brodalumab whose disease did not respond to 1, 2, or ≥3 prior biologics were 359.0, 297.6, and 383.2, respectively (table 1) acknowledgments: this study was sponsored by ortho dermatologics. medical writing support was provided by medthink scicom and funded by ortho dermatologics. ortho dermatologics is a division of bausch health us, llc. references: 1. foster et al. j manag care spec pharm. 2016;22:396-405. 2. siliq [package insert]. bridgewater, nj: valeant pharmaceuticals north america, llc; 2017. 3. lebwohl et al. n engl j med. 2015;373:1318-1328. conclusions • skin clearance rates were comparable in patients whose disease did not respond to 1, 2, or ≥3 prior biologics through week 120 • these data demonstrate that brodalumab is efficacious and well tolerated for long-term treatment of moderate-to-severe psoriasis in patients with lack of response to prior biologic therapies, including those with lack of response to ≥3 prior biologics © 2019. all rights reserved. ► ► ► ► day 1 week 12 week 16 week 52 ► week 120 ustekinumab brodalumab 210 mg q2w brodalumab 210 mg q2w ustekin umabplacebo ustekin umabustekinumab brodalumab 210 mg q2w induction maintenance long-term extension week 16 inadequate responders brodalumab 210 mg q2w brodalumab 140 mg q2w brodalumab 140 mg q4w brodalumab 140 mg q8w brodalumab 140 mg q2w r 2:2:2:1 r 2:2:1:1 brodalumab 210 mg q2w (rescue) figure 1. amagine-2/-3 study design. r, randomization; q2w, every 2 weeks; q4w, every 4 weeks; q8w, every 8 weeks. table 1. exposure-adjusted rates of teaes in patients who received any dose of brodalumab did not respond to 1 prior biologic n=160; 269.4 py did not respond to 2 prior biologics n=112; 189.2 py did not respond to ≥3 prior biologics n=136; 215.0 py grade ≥2 535 (198.6) 317 (167.6) 430 (200.0) grade ≥3 37 (13.7) 24 (12.7) 32 (14.9) serious aes 23 (8.5) 11 (5.8) 10 (4.7) fatal aes 1 (0.4) 0 0 ae, adverse event; n, number of adverse events; n, number of patients; py, total patient-years of exposure; teae, treatment-emergent adverse event. values are the number of aes (exposureadjusted event rate per 100 patient-years). weeks 12 24 36 52 72 84 96 108 1200 weeks 12 24 36 52 72 84 96 108 1200 87.2 84.3 85.3 93.2 0 20 40 60 80 100 r es po nd er s, % did not respond to 1 prior biologic did not respond to 2 prior biologics did not respond to ≥3 prior biologics did not respond to 1 prior biologic did not respond to 2 prior biologics did not respond to ≥3 prior biologics did not respond to 1 prior biologic did not respond to 2 prior biologics did not respond to ≥3 prior biologics n1 = 160 156 147 142 118 120 117 113 97 78 n1 = 112 109 102 93 86 85 78 79 66 51 n1 = 136 134 122 114 102 95 94 90 81 59 a 71.2 64.1 75.6 74.5 72.5 79.7 0 20 40 60 80 100 r es po nd er s, % n1 = 160 156 147 142 118 120 117 113 97 78 n1 = 112 109 102 93 86 85 78 79 66 51 n1 = 136 134 122 114 102 95 94 90 81 59 b 42.4 50.0 50.0 54.9 41.2 54.2 0 20 40 60 80 100 r es po nd er s, % n1 = 160 156 147 142 118 120 117 113 97 78 n1 = 112 109 102 93 86 85 78 79 66 51 n1 = 136 134 122 114 102 95 94 90 81 59 c 82.1 weeks 12 24 36 52 72 84 96 108 1200 86.4 figure 2. pasi 75 (a), pasi 90 (b), and pasi 100 (c) responses in patients whose disease did not respond to 1, 2, or ≥3 prior biologics. error bars indicate the 95% confidence interval. n1, number of patients who had a valid measurement value at the specified week; pasi 75, 90, and 100, psoriasis area and severity index 75%, 90%, and 100% improvement. optimizing the treatment sequence: the cumulative clinical benefi t of treatment initiation with deucravacitinib versus apremilast over 52 weeks in patients with moderate to severe plaque psoriasis from the poetyk pso-1 trial april w. armstrong,1 sang hee park,2 viktor chirikov,3 pierre nicolas,2,4 wei-jhih wang,3 matthew j. colombo,2 vardhaman patel2 1keck school of medicine, university of southern california, los angeles, ca; 2bristol myers squibb, princeton, nj; 3open health, bethesda, md; 4bristol myers squibb, boudry, switzerland presented at the fall clinical dermatology conference; october 20—23, 2022; las vegas, nv this poster may not be reproduced without written permission from the authors.email for april armstrong, md, mph: aprilarmstrong@post.harvard.edu scientifi c content on demand to request a copy of this poster: scan qr code via a barcode reader application qr codes are valid for 30 days after congress presentation date synopsis • deucravacitinib is an oral, selective, allosteric tyrosine kinase 2 inhibitor approved by the us food and drug administration for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy • in the recent phase 3 clinical trial poetyk pso-1, patients with moderate to severe plaque psoriasis were randomized 2:1:1 to deucravacitinib, placebo, or apremilast1 — patients receiving apremilast who did not achieve at least 50% improvement from baseline in psoriasis area and severity index score (pasi 50) at week 24 crossed over to deucravacitinib1 • at week 52, 46.3% of these patients achieved at least 75% improvement from baseline in pasi score (pasi 75), and 42.6% achieved a static physician global assessment (spga) score of 0 or 1 (spga 0/1)2 — patients receiving apremilast who achieved pasi 50 at week 24 continued with apremilast — patients who received placebo are not represented in this analysis • this study evaluated the cumulative clinical benefit of initiating with deucravacitinib vs apremilast to determine the treatment pathway that provides greater benefit to the patient — the cumulative clinical benefit refl ects the total time patients spend in a state of therapeutic response3 • the results of this study indicate that initiating deucravacitinib as a first-line treatment offers greater benefits over time compared with initiating with apremilast objective • to evaluate the cumulative clinical benefit of initiating with deucravacitinib vs apremilast from baseline to week 52 based on data from poetyk pso-1 methods • poetyk pso-1 was a multicenter, randomized, double-blind, placeboand active comparator–controlled study1 — patients were aged ≥18 years and had moderate to severe plaque psoriasis (pasi score ≥12, spga score ≥3, and body surface area involvement ≥10%) — coprimary effi cacy endpoints were pasi 75 and spga 0/1 — nonresponder imputation was used for missing data • this post hoc analysis compared data from 2 arms in the poetyk pso-1 trial (figure 1) — deucravacitinib arm: patients initiated with and continued on deucravacitinib, regardless of response status — apremilast initiators arm: patients initiated with apremilast; at week 24, pasi 50 responders continued with apremilast while pasi 50 nonresponders crossed over to deucravacitinib • cumulative clinical benefit from randomization to week 52 was determined by the total area under the curve of clinical response over 52 weeks (auc 0–52wk ) in each arm — auc analysis has been employed to evaluate outcomes over time in clinical trials, as the auc refl ects the rapidity and durability, as well as the magnitude, of response3-6 • while assessments at discrete time points identify static responses, the auc approach captures cumulative treatment effects over time — this study determined the auc using data at a patient level (responder status at each time point over 52 weeks) • total auc 0–52wk was calculated separately for each efficacy endpoint, using the trapezoidal rule — total auc 0–52wk = 15i=0∑ (pi+pi+1)(ti+1−ti), where ti (i = 0, 1, 2, 3, …, 15) denotes the time points of weeks 0, 1, 2, 4, 8, 12, and 16, then every 4 weeks thereafter through week 52, and p i denotes the response (yes = 1; no = 0) at each time point, t i • the result was standardized as a percentage of maximum possible auc 0–52wk (0–5200 [% × weeks]) and aggregated to the population level • adjusted auc comparisons between the 2 treatment arms were based on an analysis of covariance (ancova) model, with the following stratification parameters: — prior use of a biologic treatment (yes/no) — region (united states, china, japan, rest of the world [row]) — body weight (<90 kg, ≥90 kg), in the united states and row only • ratios of auc 0–52wk were calculated, representing the relative cumulative clinical benefit of the 2 treatment pathways for achieving pasi 75 or spga 0/1 over the 52-week period figure 1. study design comparing data from 2 arms of poetyk pso-1 week 0 week 24 week 52 apremilast initiators arm (n = 168) deucravacitinib arm (n = 332) initiation of deucravacitinib continuation of deucravacitinib initiation of apremilast ≥pasi 50: continuation of apremilast <pasi 50: initiation of deucravacitinib pasi 50, 50% improvement from baseline in psoriasis area and severity index score. results pasi 75 • standardized average cumulative pasi 75 response over 52 weeks among patients initiating with deucravacitinib was 57.3% compared with 38.2% in patients initiating with apremilast (including 87 patients who continued apremilast after week 24 and 54 patients who switched to deucravacitinib) (table 1) — adjusted auc 0–52wk [% × weeks] was 2978.72 in the deucravacitinib arm and 1988.06 in the apremilast initiatiors arm — the adjusted difference in auc 0–52wk was 990.66 (95% ci, 683.37–1297.95); p < 0.001 — the benefit ratio of initiating with deucravacitinib vs apremilast was 1.50 • figure 2 displays the standardized adjusted cumulative auc for pasi 75 over 52 weeks spga 0/1 • standardized average cumulative spga 0/1 response over 52 weeks among patients initiating with deucravacitinib was 50.2% compared with 31.9% in patients initiating with apremilast (table 2) — adjusted auc 0–52wk [% × weeks] was 2612.82 in the deucravacitinib arm and 1657.13 in the apremilast initiators arm — the adjusted difference in auc 0–52wk was 955.69 (95% ci, 642.22–1269.16); p < 0.001 — the benefit ratio of initiating with deucravacitinib vs apremilast was 1.58 • figure 3 displays the standardized adjusted cumulative auc for spga 0/1 over 52 weeks table 1. cumulative clinical benefit measured by pasi 75 response over 52 weeks outcomes deucravacitinib, n = 332 apremilast initiators,a n = 168 difference in estimate (95% ci) p value benefit ratio adjusted auc 0–52wk , % × weeks 2978.72 1988.06 990.66 (683.37–1297.95) < 0.001 1.50 standardized average cumulative responseb 57.3% 38.2% — — aamong patients initiating with apremilast, 87 achieved pasi 50 at week 24 and continued receiving apremilast, and 54 did not achieve pasi 50 and switched to deucravacitinib. bauc 0–52wk /maximum auc 0–52wk . auc 0–52wk , area under the curve over 52 weeks; ci, confidence interval; pasi 75, 75% improvement from baseline in psoriasis area and severity index score. figure 2. standardized adjusted auc 0–52wk : pasi 75 0 10 20 30 40 50 60 st an d ar d iz e d a ve ra ge c u m u la ti ve r e sp o n se , % weeks 0 4 8 12 16 20 24 28 32 36 40 44 48 52 deucravacitinib (n = 332) apremilast initiators (n = 168)a aamong patients initiating with apremilast, 87 achieved pasi 50 at week 24 and continued receiving apremilast, and 54 did not achieve pasi 50 and switched to deucravacitinib. auc 0–52wk , area under the curve over 52 weeks; pasi 50/75, ≥50%/≥75% improvement from baseline in psoriasis area and severity index score. table 2. cumulative clinical benefit measured by spga 0/1 response over 52 weeks outcomes deucravacitinib, n = 332 apremilast initiators,a n = 168 difference in estimate (95% ci) p value benefit ratio adjusted auc 0–52wk , % × weeks 2612.82 1657.13 955.69 (642.22–1269.16) < 0.001 1.58 standardized average cumulative responseb 50.2% 31.9% — — aamong patients initiating with apremilast, 87 achieved pasi 50 at week 24 and continued receiving apremilast, and 54 did not achieve pasi 50 and switched to deucravacitinib. bauc 0–52wk /maximum auc 0–52wk . auc 0–52wk , area under the curve over 52 weeks; ci, confidence interval; spga 0/1, static physician global assessment score of 0 or 1. figure 3. standardized adjusted auc 0–52wk : spga 0/1 deucravacitinib (n = 332) apremilast initiators (n = 168)a 0 10 20 30 40 50 60 st an d ar d iz e d a ve ra ge c u m u la ti ve r e sp o n se , % weeks 0 4 8 12 16 20 24 28 32 36 40 44 48 52 aamong patients initiating with apremilast, 87 achieved pasi 50 at week 24 and continued receiving apremilast, and 54 did not achieve pasi 50 and switched to deucravacitinib. auc 0–52wk , area under the curve over 52 weeks; pasi 50, ≥50% improvement from baseline in psoriasis area and severity index score; spga, static physician global assessment score of 0 or 1. conclusions • initiating with deucravacitinib resulted in greater cumulative benefits over 52 weeks than initiating with apremilast — deucravacitinib initiators spend ≈150% more time in therapeutic response over 1 year compared with apremilast initiators • initiating with deucravacitinib as the first line rather than switching to deucravacitinib as the second line after failure to respond with apremilast may optimize the clinical benefit that patients receive references 1. armstrong aw, et al. j am acad dermatol. 2022;s0190-9622 [online ahead of print]. 2. armstrong aw, et al. [poster] presented at the american academy of dermatology annual meeting, march 25–29, 2022, boston, ma. 3. armstrong aw, et al. j dermatolog treat. 2017;28:200-205. 4. bushmakin ag, et al. qual life res. 2011;20:491-498. 5. warren rb, et al. j eur acad dermatol venereol. 2021;35:450-457. 6. blauvelt a, et al. j manag care spec pharm. 2021;27:84-94. acknowledgments • this study was supported by bristol myers squibb • medical writing and editorial assistance was provided by eleanor bush, ma, of peloton advantage, llc, an open health company, and funded by bristol myers squibb disclosures • awa: grants and personal fees: abbvie, bristol myers squibb, eli lilly, janssen, leo pharma, and novartis; personal fees: boehringer ingelheim/parexel, celgene, dermavant, genentech, glaxosmithkline, menlo therapeutics, merck, modernizing medicine, ortho dermatologics, pfizer, regeneron, sanofi genzyme, science 37, sun pharma, and valeant; grants: dermira, kyowa hakko kirin, and ucb, outside the submitted work • shp, vp, pn, mjc: employees of and may own stock options in bristol myers squibb • w-jw, vc: employees of open health, which has received consulting fees from bristol myers squibb 1 2 optimizing the treatment sequence: the cumulative clinical benefi t of treatment initiation with deucravacitinib versus apremilast over 52 weeks in patients with moderate to severe plaque psoriasis from the poetyk pso-1 trial april w. armstrong,1 sang hee park,2 viktor chirikov,3 pierre nicolas,2,4 wei-jhih wang,3 matthew j. colombo,2 vardhaman patel2 1keck school of medicine, university of southern california, los angeles, ca; 2bristol myers squibb, princeton, nj; 3open health, bethesda, md; 4bristol myers squibb, boudry, switzerland presented at the fall clinical dermatology conference; october 20—23, 2022; las vegas, nv this poster may not be reproduced without written permission from the authors.email for april armstrong, md, mph: aprilarmstrong@post.harvard.edu scientifi c content on demand to request a copy of this poster: scan qr code via a barcode reader application qr codes are valid for 30 days after congress presentation date synopsis • deucravacitinib is an oral, selective, allosteric tyrosine kinase 2 inhibitor approved by the us food and drug administration for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy • in the recent phase 3 clinical trial poetyk pso-1, patients with moderate to severe plaque psoriasis were randomized 2:1:1 to deucravacitinib, placebo, or apremilast1 — patients receiving apremilast who did not achieve at least 50% improvement from baseline in psoriasis area and severity index score (pasi 50) at week 24 crossed over to deucravacitinib1 • at week 52, 46.3% of these patients achieved at least 75% improvement from baseline in pasi score (pasi 75), and 42.6% achieved a static physician global assessment (spga) score of 0 or 1 (spga 0/1)2 — patients receiving apremilast who achieved pasi 50 at week 24 continued with apremilast — patients who received placebo are not represented in this analysis • this study evaluated the cumulative clinical benefit of initiating with deucravacitinib vs apremilast to determine the treatment pathway that provides greater benefit to the patient — the cumulative clinical benefit refl ects the total time patients spend in a state of therapeutic response3 • the results of this study indicate that initiating deucravacitinib as a first-line treatment offers greater benefits over time compared with initiating with apremilast objective • to evaluate the cumulative clinical benefit of initiating with deucravacitinib vs apremilast from baseline to week 52 based on data from poetyk pso-1 methods • poetyk pso-1 was a multicenter, randomized, double-blind, placeboand active comparator–controlled study1 — patients were aged ≥18 years and had moderate to severe plaque psoriasis (pasi score ≥12, spga score ≥3, and body surface area involvement ≥10%) — coprimary effi cacy endpoints were pasi 75 and spga 0/1 — nonresponder imputation was used for missing data • this post hoc analysis compared data from 2 arms in the poetyk pso-1 trial (figure 1) — deucravacitinib arm: patients initiated with and continued on deucravacitinib, regardless of response status — apremilast initiators arm: patients initiated with apremilast; at week 24, pasi 50 responders continued with apremilast while pasi 50 nonresponders crossed over to deucravacitinib • cumulative clinical benefit from randomization to week 52 was determined by the total area under the curve of clinical response over 52 weeks (auc 0–52wk ) in each arm — auc analysis has been employed to evaluate outcomes over time in clinical trials, as the auc refl ects the rapidity and durability, as well as the magnitude, of response3-6 • while assessments at discrete time points identify static responses, the auc approach captures cumulative treatment effects over time — this study determined the auc using data at a patient level (responder status at each time point over 52 weeks) • total auc 0–52wk was calculated separately for each efficacy endpoint, using the trapezoidal rule — total auc 0–52wk = 15i=0∑ (pi+pi+1)(ti+1−ti), where ti (i = 0, 1, 2, 3, …, 15) denotes the time points of weeks 0, 1, 2, 4, 8, 12, and 16, then every 4 weeks thereafter through week 52, and p i denotes the response (yes = 1; no = 0) at each time point, t i • the result was standardized as a percentage of maximum possible auc 0–52wk (0–5200 [% × weeks]) and aggregated to the population level • adjusted auc comparisons between the 2 treatment arms were based on an analysis of covariance (ancova) model, with the following stratification parameters: — prior use of a biologic treatment (yes/no) — region (united states, china, japan, rest of the world [row]) — body weight (<90 kg, ≥90 kg), in the united states and row only • ratios of auc 0–52wk were calculated, representing the relative cumulative clinical benefit of the 2 treatment pathways for achieving pasi 75 or spga 0/1 over the 52-week period figure 1. study design comparing data from 2 arms of poetyk pso-1 week 0 week 24 week 52 apremilast initiators arm (n = 168) deucravacitinib arm (n = 332) initiation of deucravacitinib continuation of deucravacitinib initiation of apremilast ≥pasi 50: continuation of apremilast <pasi 50: initiation of deucravacitinib pasi 50, 50% improvement from baseline in psoriasis area and severity index score. results pasi 75 • standardized average cumulative pasi 75 response over 52 weeks among patients initiating with deucravacitinib was 57.3% compared with 38.2% in patients initiating with apremilast (including 87 patients who continued apremilast after week 24 and 54 patients who switched to deucravacitinib) (table 1) — adjusted auc 0–52wk [% × weeks] was 2978.72 in the deucravacitinib arm and 1988.06 in the apremilast initiatiors arm — the adjusted difference in auc 0–52wk was 990.66 (95% ci, 683.37–1297.95); p < 0.001 — the benefit ratio of initiating with deucravacitinib vs apremilast was 1.50 • figure 2 displays the standardized adjusted cumulative auc for pasi 75 over 52 weeks spga 0/1 • standardized average cumulative spga 0/1 response over 52 weeks among patients initiating with deucravacitinib was 50.2% compared with 31.9% in patients initiating with apremilast (table 2) — adjusted auc 0–52wk [% × weeks] was 2612.82 in the deucravacitinib arm and 1657.13 in the apremilast initiators arm — the adjusted difference in auc 0–52wk was 955.69 (95% ci, 642.22–1269.16); p < 0.001 — the benefit ratio of initiating with deucravacitinib vs apremilast was 1.58 • figure 3 displays the standardized adjusted cumulative auc for spga 0/1 over 52 weeks table 1. cumulative clinical benefit measured by pasi 75 response over 52 weeks outcomes deucravacitinib, n = 332 apremilast initiators,a n = 168 difference in estimate (95% ci) p value benefit ratio adjusted auc 0–52wk , % × weeks 2978.72 1988.06 990.66 (683.37–1297.95) < 0.001 1.50 standardized average cumulative responseb 57.3% 38.2% — — aamong patients initiating with apremilast, 87 achieved pasi 50 at week 24 and continued receiving apremilast, and 54 did not achieve pasi 50 and switched to deucravacitinib. bauc 0–52wk /maximum auc 0–52wk . auc 0–52wk , area under the curve over 52 weeks; ci, confidence interval; pasi 75, 75% improvement from baseline in psoriasis area and severity index score. figure 2. standardized adjusted auc 0–52wk : pasi 75 0 10 20 30 40 50 60 st an d ar d iz e d a ve ra ge c u m u la ti ve r e sp o n se , % weeks 0 4 8 12 16 20 24 28 32 36 40 44 48 52 deucravacitinib (n = 332) apremilast initiators (n = 168)a aamong patients initiating with apremilast, 87 achieved pasi 50 at week 24 and continued receiving apremilast, and 54 did not achieve pasi 50 and switched to deucravacitinib. auc 0–52wk , area under the curve over 52 weeks; pasi 50/75, ≥50%/≥75% improvement from baseline in psoriasis area and severity index score. table 2. cumulative clinical benefit measured by spga 0/1 response over 52 weeks outcomes deucravacitinib, n = 332 apremilast initiators,a n = 168 difference in estimate (95% ci) p value benefit ratio adjusted auc 0–52wk , % × weeks 2612.82 1657.13 955.69 (642.22–1269.16) < 0.001 1.58 standardized average cumulative responseb 50.2% 31.9% — — aamong patients initiating with apremilast, 87 achieved pasi 50 at week 24 and continued receiving apremilast, and 54 did not achieve pasi 50 and switched to deucravacitinib. bauc 0–52wk /maximum auc 0–52wk . auc 0–52wk , area under the curve over 52 weeks; ci, confidence interval; spga 0/1, static physician global assessment score of 0 or 1. figure 3. standardized adjusted auc 0–52wk : spga 0/1 deucravacitinib (n = 332) apremilast initiators (n = 168)a 0 10 20 30 40 50 60 st an d ar d iz e d a ve ra ge c u m u la ti ve r e sp o n se , % weeks 0 4 8 12 16 20 24 28 32 36 40 44 48 52 aamong patients initiating with apremilast, 87 achieved pasi 50 at week 24 and continued receiving apremilast, and 54 did not achieve pasi 50 and switched to deucravacitinib. auc 0–52wk , area under the curve over 52 weeks; pasi 50, ≥50% improvement from baseline in psoriasis area and severity index score; spga, static physician global assessment score of 0 or 1. conclusions • initiating with deucravacitinib resulted in greater cumulative benefits over 52 weeks than initiating with apremilast — deucravacitinib initiators spend ≈150% more time in therapeutic response over 1 year compared with apremilast initiators • initiating with deucravacitinib as the first line rather than switching to deucravacitinib as the second line after failure to respond with apremilast may optimize the clinical benefit that patients receive references 1. armstrong aw, et al. j am acad dermatol. 2022;s0190-9622 [online ahead of print]. 2. armstrong aw, et al. [poster] presented at the american academy of dermatology annual meeting, march 25–29, 2022, boston, ma. 3. armstrong aw, et al. j dermatolog treat. 2017;28:200-205. 4. bushmakin ag, et al. qual life res. 2011;20:491-498. 5. warren rb, et al. j eur acad dermatol venereol. 2021;35:450-457. 6. blauvelt a, et al. j manag care spec pharm. 2021;27:84-94. acknowledgments • this study was supported by bristol myers squibb • medical writing and editorial assistance was provided by eleanor bush, ma, of peloton advantage, llc, an open health company, and funded by bristol myers squibb disclosures • awa: grants and personal fees: abbvie, bristol myers squibb, eli lilly, janssen, leo pharma, and novartis; personal fees: boehringer ingelheim/parexel, celgene, dermavant, genentech, glaxosmithkline, menlo therapeutics, merck, modernizing medicine, ortho dermatologics, pfizer, regeneron, sanofi genzyme, science 37, sun pharma, and valeant; grants: dermira, kyowa hakko kirin, and ucb, outside the submitted work • shp, vp, pn, mjc: employees of and may own stock options in bristol myers squibb • w-jw, vc: employees of open health, which has received consulting fees from bristol myers squibb 1 2 optimizing the treatment sequence: the cumulative clinical benefi t of treatment initiation with deucravacitinib versus apremilast over 52 weeks in patients with moderate to severe plaque psoriasis from the poetyk pso-1 trial april w. armstrong,1 sang hee park,2 viktor chirikov,3 pierre nicolas,2,4 wei-jhih wang,3 matthew j. colombo,2 vardhaman patel2 1keck school of medicine, university of southern california, los angeles, ca; 2bristol myers squibb, princeton, nj; 3open health, bethesda, md; 4bristol myers squibb, boudry, switzerland presented at the fall clinical dermatology conference; october 20—23, 2022; las vegas, nv this poster may not be reproduced without written permission from the authors.email for april armstrong, md, mph: aprilarmstrong@post.harvard.edu scientifi c content on demand to request a copy of this poster: scan qr code via a barcode reader application qr codes are valid for 30 days after congress presentation date synopsis • deucravacitinib is an oral, selective, allosteric tyrosine kinase 2 inhibitor approved by the us food and drug administration for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy • in the recent phase 3 clinical trial poetyk pso-1, patients with moderate to severe plaque psoriasis were randomized 2:1:1 to deucravacitinib, placebo, or apremilast1 — patients receiving apremilast who did not achieve at least 50% improvement from baseline in psoriasis area and severity index score (pasi 50) at week 24 crossed over to deucravacitinib1 • at week 52, 46.3% of these patients achieved at least 75% improvement from baseline in pasi score (pasi 75), and 42.6% achieved a static physician global assessment (spga) score of 0 or 1 (spga 0/1)2 — patients receiving apremilast who achieved pasi 50 at week 24 continued with apremilast — patients who received placebo are not represented in this analysis • this study evaluated the cumulative clinical benefit of initiating with deucravacitinib vs apremilast to determine the treatment pathway that provides greater benefit to the patient — the cumulative clinical benefit refl ects the total time patients spend in a state of therapeutic response3 • the results of this study indicate that initiating deucravacitinib as a first-line treatment offers greater benefits over time compared with initiating with apremilast objective • to evaluate the cumulative clinical benefit of initiating with deucravacitinib vs apremilast from baseline to week 52 based on data from poetyk pso-1 methods • poetyk pso-1 was a multicenter, randomized, double-blind, placeboand active comparator–controlled study1 — patients were aged ≥18 years and had moderate to severe plaque psoriasis (pasi score ≥12, spga score ≥3, and body surface area involvement ≥10%) — coprimary effi cacy endpoints were pasi 75 and spga 0/1 — nonresponder imputation was used for missing data • this post hoc analysis compared data from 2 arms in the poetyk pso-1 trial (figure 1) — deucravacitinib arm: patients initiated with and continued on deucravacitinib, regardless of response status — apremilast initiators arm: patients initiated with apremilast; at week 24, pasi 50 responders continued with apremilast while pasi 50 nonresponders crossed over to deucravacitinib • cumulative clinical benefit from randomization to week 52 was determined by the total area under the curve of clinical response over 52 weeks (auc 0–52wk ) in each arm — auc analysis has been employed to evaluate outcomes over time in clinical trials, as the auc refl ects the rapidity and durability, as well as the magnitude, of response3-6 • while assessments at discrete time points identify static responses, the auc approach captures cumulative treatment effects over time — this study determined the auc using data at a patient level (responder status at each time point over 52 weeks) • total auc 0–52wk was calculated separately for each efficacy endpoint, using the trapezoidal rule — total auc 0–52wk = 15i=0∑ (pi+pi+1)(ti+1−ti), where ti (i = 0, 1, 2, 3, …, 15) denotes the time points of weeks 0, 1, 2, 4, 8, 12, and 16, then every 4 weeks thereafter through week 52, and p i denotes the response (yes = 1; no = 0) at each time point, t i • the result was standardized as a percentage of maximum possible auc 0–52wk (0–5200 [% × weeks]) and aggregated to the population level • adjusted auc comparisons between the 2 treatment arms were based on an analysis of covariance (ancova) model, with the following stratification parameters: — prior use of a biologic treatment (yes/no) — region (united states, china, japan, rest of the world [row]) — body weight (<90 kg, ≥90 kg), in the united states and row only • ratios of auc 0–52wk were calculated, representing the relative cumulative clinical benefit of the 2 treatment pathways for achieving pasi 75 or spga 0/1 over the 52-week period figure 1. study design comparing data from 2 arms of poetyk pso-1 week 0 week 24 week 52 apremilast initiators arm (n = 168) deucravacitinib arm (n = 332) initiation of deucravacitinib continuation of deucravacitinib initiation of apremilast ≥pasi 50: continuation of apremilast <pasi 50: initiation of deucravacitinib pasi 50, 50% improvement from baseline in psoriasis area and severity index score. results pasi 75 • standardized average cumulative pasi 75 response over 52 weeks among patients initiating with deucravacitinib was 57.3% compared with 38.2% in patients initiating with apremilast (including 87 patients who continued apremilast after week 24 and 54 patients who switched to deucravacitinib) (table 1) — adjusted auc 0–52wk [% × weeks] was 2978.72 in the deucravacitinib arm and 1988.06 in the apremilast initiatiors arm — the adjusted difference in auc 0–52wk was 990.66 (95% ci, 683.37–1297.95); p < 0.001 — the benefit ratio of initiating with deucravacitinib vs apremilast was 1.50 • figure 2 displays the standardized adjusted cumulative auc for pasi 75 over 52 weeks spga 0/1 • standardized average cumulative spga 0/1 response over 52 weeks among patients initiating with deucravacitinib was 50.2% compared with 31.9% in patients initiating with apremilast (table 2) — adjusted auc 0–52wk [% × weeks] was 2612.82 in the deucravacitinib arm and 1657.13 in the apremilast initiators arm — the adjusted difference in auc 0–52wk was 955.69 (95% ci, 642.22–1269.16); p < 0.001 — the benefit ratio of initiating with deucravacitinib vs apremilast was 1.58 • figure 3 displays the standardized adjusted cumulative auc for spga 0/1 over 52 weeks table 1. cumulative clinical benefit measured by pasi 75 response over 52 weeks outcomes deucravacitinib, n = 332 apremilast initiators,a n = 168 difference in estimate (95% ci) p value benefit ratio adjusted auc 0–52wk , % × weeks 2978.72 1988.06 990.66 (683.37–1297.95) < 0.001 1.50 standardized average cumulative responseb 57.3% 38.2% — — aamong patients initiating with apremilast, 87 achieved pasi 50 at week 24 and continued receiving apremilast, and 54 did not achieve pasi 50 and switched to deucravacitinib. bauc 0–52wk /maximum auc 0–52wk . auc 0–52wk , area under the curve over 52 weeks; ci, confidence interval; pasi 75, 75% improvement from baseline in psoriasis area and severity index score. figure 2. standardized adjusted auc 0–52wk : pasi 75 0 10 20 30 40 50 60 st an d ar d iz e d a ve ra ge c u m u la ti ve r e sp o n se , % weeks 0 4 8 12 16 20 24 28 32 36 40 44 48 52 deucravacitinib (n = 332) apremilast initiators (n = 168)a aamong patients initiating with apremilast, 87 achieved pasi 50 at week 24 and continued receiving apremilast, and 54 did not achieve pasi 50 and switched to deucravacitinib. auc 0–52wk , area under the curve over 52 weeks; pasi 50/75, ≥50%/≥75% improvement from baseline in psoriasis area and severity index score. table 2. cumulative clinical benefit measured by spga 0/1 response over 52 weeks outcomes deucravacitinib, n = 332 apremilast initiators,a n = 168 difference in estimate (95% ci) p value benefit ratio adjusted auc 0–52wk , % × weeks 2612.82 1657.13 955.69 (642.22–1269.16) < 0.001 1.58 standardized average cumulative responseb 50.2% 31.9% — — aamong patients initiating with apremilast, 87 achieved pasi 50 at week 24 and continued receiving apremilast, and 54 did not achieve pasi 50 and switched to deucravacitinib. bauc 0–52wk /maximum auc 0–52wk . auc 0–52wk , area under the curve over 52 weeks; ci, confidence interval; spga 0/1, static physician global assessment score of 0 or 1. figure 3. standardized adjusted auc 0–52wk : spga 0/1 deucravacitinib (n = 332) apremilast initiators (n = 168)a 0 10 20 30 40 50 60 st an d ar d iz e d a ve ra ge c u m u la ti ve r e sp o n se , % weeks 0 4 8 12 16 20 24 28 32 36 40 44 48 52 aamong patients initiating with apremilast, 87 achieved pasi 50 at week 24 and continued receiving apremilast, and 54 did not achieve pasi 50 and switched to deucravacitinib. auc 0–52wk , area under the curve over 52 weeks; pasi 50, ≥50% improvement from baseline in psoriasis area and severity index score; spga, static physician global assessment score of 0 or 1. conclusions • initiating with deucravacitinib resulted in greater cumulative benefits over 52 weeks than initiating with apremilast — deucravacitinib initiators spend ≈150% more time in therapeutic response over 1 year compared with apremilast initiators • initiating with deucravacitinib as the first line rather than switching to deucravacitinib as the second line after failure to respond with apremilast may optimize the clinical benefit that patients receive references 1. armstrong aw, et al. j am acad dermatol. 2022;s0190-9622 [online ahead of print]. 2. armstrong aw, et al. [poster] presented at the american academy of dermatology annual meeting, march 25–29, 2022, boston, ma. 3. armstrong aw, et al. j dermatolog treat. 2017;28:200-205. 4. bushmakin ag, et al. qual life res. 2011;20:491-498. 5. warren rb, et al. j eur acad dermatol venereol. 2021;35:450-457. 6. blauvelt a, et al. j manag care spec pharm. 2021;27:84-94. acknowledgments • this study was supported by bristol myers squibb • medical writing and editorial assistance was provided by eleanor bush, ma, of peloton advantage, llc, an open health company, and funded by bristol myers squibb disclosures • awa: grants and personal fees: abbvie, bristol myers squibb, eli lilly, janssen, leo pharma, and novartis; personal fees: boehringer ingelheim/parexel, celgene, dermavant, genentech, glaxosmithkline, menlo therapeutics, merck, modernizing medicine, ortho dermatologics, pfizer, regeneron, sanofi genzyme, science 37, sun pharma, and valeant; grants: dermira, kyowa hakko kirin, and ucb, outside the submitted work • shp, vp, pn, mjc: employees of and may own stock options in bristol myers squibb • w-jw, vc: employees of open health, which has received consulting fees from bristol myers squibb 1 2 optimizing the treatment sequence: the cumulative clinical benefi t of treatment initiation with deucravacitinib versus apremilast over 52 weeks in patients with moderate to severe plaque psoriasis from the poetyk pso-1 trial april w. armstrong,1 sang hee park,2 viktor chirikov,3 pierre nicolas,2,4 wei-jhih wang,3 matthew j. colombo,2 vardhaman patel2 1keck school of medicine, university of southern california, los angeles, ca; 2bristol myers squibb, princeton, nj; 3open health, bethesda, md; 4bristol myers squibb, boudry, switzerland presented at the fall clinical dermatology conference; october 20—23, 2022; las vegas, nv this poster may not be reproduced without written permission from the authors.email for april armstrong, md, mph: aprilarmstrong@post.harvard.edu scientifi c content on demand to request a copy of this poster: scan qr code via a barcode reader application qr codes are valid for 30 days after congress presentation date synopsis • deucravacitinib is an oral, selective, allosteric tyrosine kinase 2 inhibitor approved by the us food and drug administration for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy • in the recent phase 3 clinical trial poetyk pso-1, patients with moderate to severe plaque psoriasis were randomized 2:1:1 to deucravacitinib, placebo, or apremilast1 — patients receiving apremilast who did not achieve at least 50% improvement from baseline in psoriasis area and severity index score (pasi 50) at week 24 crossed over to deucravacitinib1 • at week 52, 46.3% of these patients achieved at least 75% improvement from baseline in pasi score (pasi 75), and 42.6% achieved a static physician global assessment (spga) score of 0 or 1 (spga 0/1)2 — patients receiving apremilast who achieved pasi 50 at week 24 continued with apremilast — patients who received placebo are not represented in this analysis • this study evaluated the cumulative clinical benefit of initiating with deucravacitinib vs apremilast to determine the treatment pathway that provides greater benefit to the patient — the cumulative clinical benefit refl ects the total time patients spend in a state of therapeutic response3 • the results of this study indicate that initiating deucravacitinib as a first-line treatment offers greater benefits over time compared with initiating with apremilast objective • to evaluate the cumulative clinical benefit of initiating with deucravacitinib vs apremilast from baseline to week 52 based on data from poetyk pso-1 methods • poetyk pso-1 was a multicenter, randomized, double-blind, placeboand active comparator–controlled study1 — patients were aged ≥18 years and had moderate to severe plaque psoriasis (pasi score ≥12, spga score ≥3, and body surface area involvement ≥10%) — coprimary effi cacy endpoints were pasi 75 and spga 0/1 — nonresponder imputation was used for missing data • this post hoc analysis compared data from 2 arms in the poetyk pso-1 trial (figure 1) — deucravacitinib arm: patients initiated with and continued on deucravacitinib, regardless of response status — apremilast initiators arm: patients initiated with apremilast; at week 24, pasi 50 responders continued with apremilast while pasi 50 nonresponders crossed over to deucravacitinib • cumulative clinical benefit from randomization to week 52 was determined by the total area under the curve of clinical response over 52 weeks (auc 0–52wk ) in each arm — auc analysis has been employed to evaluate outcomes over time in clinical trials, as the auc refl ects the rapidity and durability, as well as the magnitude, of response3-6 • while assessments at discrete time points identify static responses, the auc approach captures cumulative treatment effects over time — this study determined the auc using data at a patient level (responder status at each time point over 52 weeks) • total auc 0–52wk was calculated separately for each efficacy endpoint, using the trapezoidal rule — total auc 0–52wk = 15i=0∑ (pi+pi+1)(ti+1−ti), where ti (i = 0, 1, 2, 3, …, 15) denotes the time points of weeks 0, 1, 2, 4, 8, 12, and 16, then every 4 weeks thereafter through week 52, and p i denotes the response (yes = 1; no = 0) at each time point, t i • the result was standardized as a percentage of maximum possible auc 0–52wk (0–5200 [% × weeks]) and aggregated to the population level • adjusted auc comparisons between the 2 treatment arms were based on an analysis of covariance (ancova) model, with the following stratification parameters: — prior use of a biologic treatment (yes/no) — region (united states, china, japan, rest of the world [row]) — body weight (<90 kg, ≥90 kg), in the united states and row only • ratios of auc 0–52wk were calculated, representing the relative cumulative clinical benefit of the 2 treatment pathways for achieving pasi 75 or spga 0/1 over the 52-week period figure 1. study design comparing data from 2 arms of poetyk pso-1 week 0 week 24 week 52 apremilast initiators arm (n = 168) deucravacitinib arm (n = 332) initiation of deucravacitinib continuation of deucravacitinib initiation of apremilast ≥pasi 50: continuation of apremilast <pasi 50: initiation of deucravacitinib pasi 50, 50% improvement from baseline in psoriasis area and severity index score. results pasi 75 • standardized average cumulative pasi 75 response over 52 weeks among patients initiating with deucravacitinib was 57.3% compared with 38.2% in patients initiating with apremilast (including 87 patients who continued apremilast after week 24 and 54 patients who switched to deucravacitinib) (table 1) — adjusted auc 0–52wk [% × weeks] was 2978.72 in the deucravacitinib arm and 1988.06 in the apremilast initiatiors arm — the adjusted difference in auc 0–52wk was 990.66 (95% ci, 683.37–1297.95); p < 0.001 — the benefit ratio of initiating with deucravacitinib vs apremilast was 1.50 • figure 2 displays the standardized adjusted cumulative auc for pasi 75 over 52 weeks spga 0/1 • standardized average cumulative spga 0/1 response over 52 weeks among patients initiating with deucravacitinib was 50.2% compared with 31.9% in patients initiating with apremilast (table 2) — adjusted auc 0–52wk [% × weeks] was 2612.82 in the deucravacitinib arm and 1657.13 in the apremilast initiators arm — the adjusted difference in auc 0–52wk was 955.69 (95% ci, 642.22–1269.16); p < 0.001 — the benefit ratio of initiating with deucravacitinib vs apremilast was 1.58 • figure 3 displays the standardized adjusted cumulative auc for spga 0/1 over 52 weeks table 1. cumulative clinical benefit measured by pasi 75 response over 52 weeks outcomes deucravacitinib, n = 332 apremilast initiators,a n = 168 difference in estimate (95% ci) p value benefit ratio adjusted auc 0–52wk , % × weeks 2978.72 1988.06 990.66 (683.37–1297.95) < 0.001 1.50 standardized average cumulative responseb 57.3% 38.2% — — aamong patients initiating with apremilast, 87 achieved pasi 50 at week 24 and continued receiving apremilast, and 54 did not achieve pasi 50 and switched to deucravacitinib. bauc 0–52wk /maximum auc 0–52wk . auc 0–52wk , area under the curve over 52 weeks; ci, confidence interval; pasi 75, 75% improvement from baseline in psoriasis area and severity index score. figure 2. standardized adjusted auc 0–52wk : pasi 75 0 10 20 30 40 50 60 st an d ar d iz e d a ve ra ge c u m u la ti ve r e sp o n se , % weeks 0 4 8 12 16 20 24 28 32 36 40 44 48 52 deucravacitinib (n = 332) apremilast initiators (n = 168)a aamong patients initiating with apremilast, 87 achieved pasi 50 at week 24 and continued receiving apremilast, and 54 did not achieve pasi 50 and switched to deucravacitinib. auc 0–52wk , area under the curve over 52 weeks; pasi 50/75, ≥50%/≥75% improvement from baseline in psoriasis area and severity index score. table 2. cumulative clinical benefit measured by spga 0/1 response over 52 weeks outcomes deucravacitinib, n = 332 apremilast initiators,a n = 168 difference in estimate (95% ci) p value benefit ratio adjusted auc 0–52wk , % × weeks 2612.82 1657.13 955.69 (642.22–1269.16) < 0.001 1.58 standardized average cumulative responseb 50.2% 31.9% — — aamong patients initiating with apremilast, 87 achieved pasi 50 at week 24 and continued receiving apremilast, and 54 did not achieve pasi 50 and switched to deucravacitinib. bauc 0–52wk /maximum auc 0–52wk . auc 0–52wk , area under the curve over 52 weeks; ci, confidence interval; spga 0/1, static physician global assessment score of 0 or 1. figure 3. standardized adjusted auc 0–52wk : spga 0/1 deucravacitinib (n = 332) apremilast initiators (n = 168)a 0 10 20 30 40 50 60 st an d ar d iz e d a ve ra ge c u m u la ti ve r e sp o n se , % weeks 0 4 8 12 16 20 24 28 32 36 40 44 48 52 aamong patients initiating with apremilast, 87 achieved pasi 50 at week 24 and continued receiving apremilast, and 54 did not achieve pasi 50 and switched to deucravacitinib. auc 0–52wk , area under the curve over 52 weeks; pasi 50, ≥50% improvement from baseline in psoriasis area and severity index score; spga, static physician global assessment score of 0 or 1. conclusions • initiating with deucravacitinib resulted in greater cumulative benefits over 52 weeks than initiating with apremilast — deucravacitinib initiators spend ≈150% more time in therapeutic response over 1 year compared with apremilast initiators • initiating with deucravacitinib as the first line rather than switching to deucravacitinib as the second line after failure to respond with apremilast may optimize the clinical benefit that patients receive references 1. armstrong aw, et al. j am acad dermatol. 2022;s0190-9622 [online ahead of print]. 2. armstrong aw, et al. [poster] presented at the american academy of dermatology annual meeting, march 25–29, 2022, boston, ma. 3. armstrong aw, et al. j dermatolog treat. 2017;28:200-205. 4. bushmakin ag, et al. qual life res. 2011;20:491-498. 5. warren rb, et al. j eur acad dermatol venereol. 2021;35:450-457. 6. blauvelt a, et al. j manag care spec pharm. 2021;27:84-94. acknowledgments • this study was supported by bristol myers squibb • medical writing and editorial assistance was provided by eleanor bush, ma, of peloton advantage, llc, an open health company, and funded by bristol myers squibb disclosures • awa: grants and personal fees: abbvie, bristol myers squibb, eli lilly, janssen, leo pharma, and novartis; personal fees: boehringer ingelheim/parexel, celgene, dermavant, genentech, glaxosmithkline, menlo therapeutics, merck, modernizing medicine, ortho dermatologics, pfizer, regeneron, sanofi genzyme, science 37, sun pharma, and valeant; grants: dermira, kyowa hakko kirin, and ucb, outside the submitted work • shp, vp, pn, mjc: employees of and may own stock options in bristol myers squibb • w-jw, vc: employees of open health, which has received consulting fees from bristol myers squibb 1 2 optimizing the treatment sequence: the cumulative clinical benefi t of treatment initiation with deucravacitinib versus apremilast over 52 weeks in patients with moderate to severe plaque psoriasis from the poetyk pso-1 trial april w. armstrong,1 sang hee park,2 viktor chirikov,3 pierre nicolas,2,4 wei-jhih wang,3 matthew j. colombo,2 vardhaman patel2 1keck school of medicine, university of southern california, los angeles, ca; 2bristol myers squibb, princeton, nj; 3open health, bethesda, md; 4bristol myers squibb, boudry, switzerland presented at the fall clinical dermatology conference; october 20—23, 2022; las vegas, nv this poster may not be reproduced without written permission from the authors.email for april armstrong, md, mph: aprilarmstrong@post.harvard.edu scientifi c content on demand to request a copy of this poster: scan qr code via a barcode reader application qr codes are valid for 30 days after congress presentation date synopsis • deucravacitinib is an oral, selective, allosteric tyrosine kinase 2 inhibitor approved by the us food and drug administration for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy • in the recent phase 3 clinical trial poetyk pso-1, patients with moderate to severe plaque psoriasis were randomized 2:1:1 to deucravacitinib, placebo, or apremilast1 — patients receiving apremilast who did not achieve at least 50% improvement from baseline in psoriasis area and severity index score (pasi 50) at week 24 crossed over to deucravacitinib1 • at week 52, 46.3% of these patients achieved at least 75% improvement from baseline in pasi score (pasi 75), and 42.6% achieved a static physician global assessment (spga) score of 0 or 1 (spga 0/1)2 — patients receiving apremilast who achieved pasi 50 at week 24 continued with apremilast — patients who received placebo are not represented in this analysis • this study evaluated the cumulative clinical benefit of initiating with deucravacitinib vs apremilast to determine the treatment pathway that provides greater benefit to the patient — the cumulative clinical benefit refl ects the total time patients spend in a state of therapeutic response3 • the results of this study indicate that initiating deucravacitinib as a first-line treatment offers greater benefits over time compared with initiating with apremilast objective • to evaluate the cumulative clinical benefit of initiating with deucravacitinib vs apremilast from baseline to week 52 based on data from poetyk pso-1 methods • poetyk pso-1 was a multicenter, randomized, double-blind, placeboand active comparator–controlled study1 — patients were aged ≥18 years and had moderate to severe plaque psoriasis (pasi score ≥12, spga score ≥3, and body surface area involvement ≥10%) — coprimary effi cacy endpoints were pasi 75 and spga 0/1 — nonresponder imputation was used for missing data • this post hoc analysis compared data from 2 arms in the poetyk pso-1 trial (figure 1) — deucravacitinib arm: patients initiated with and continued on deucravacitinib, regardless of response status — apremilast initiators arm: patients initiated with apremilast; at week 24, pasi 50 responders continued with apremilast while pasi 50 nonresponders crossed over to deucravacitinib • cumulative clinical benefit from randomization to week 52 was determined by the total area under the curve of clinical response over 52 weeks (auc 0–52wk ) in each arm — auc analysis has been employed to evaluate outcomes over time in clinical trials, as the auc refl ects the rapidity and durability, as well as the magnitude, of response3-6 • while assessments at discrete time points identify static responses, the auc approach captures cumulative treatment effects over time — this study determined the auc using data at a patient level (responder status at each time point over 52 weeks) • total auc 0–52wk was calculated separately for each efficacy endpoint, using the trapezoidal rule — total auc 0–52wk = 15i=0∑ (pi+pi+1)(ti+1−ti), where ti (i = 0, 1, 2, 3, …, 15) denotes the time points of weeks 0, 1, 2, 4, 8, 12, and 16, then every 4 weeks thereafter through week 52, and p i denotes the response (yes = 1; no = 0) at each time point, t i • the result was standardized as a percentage of maximum possible auc 0–52wk (0–5200 [% × weeks]) and aggregated to the population level • adjusted auc comparisons between the 2 treatment arms were based on an analysis of covariance (ancova) model, with the following stratification parameters: — prior use of a biologic treatment (yes/no) — region (united states, china, japan, rest of the world [row]) — body weight (<90 kg, ≥90 kg), in the united states and row only • ratios of auc 0–52wk were calculated, representing the relative cumulative clinical benefit of the 2 treatment pathways for achieving pasi 75 or spga 0/1 over the 52-week period figure 1. study design comparing data from 2 arms of poetyk pso-1 week 0 week 24 week 52 apremilast initiators arm (n = 168) deucravacitinib arm (n = 332) initiation of deucravacitinib continuation of deucravacitinib initiation of apremilast ≥pasi 50: continuation of apremilast <pasi 50: initiation of deucravacitinib pasi 50, 50% improvement from baseline in psoriasis area and severity index score. results pasi 75 • standardized average cumulative pasi 75 response over 52 weeks among patients initiating with deucravacitinib was 57.3% compared with 38.2% in patients initiating with apremilast (including 87 patients who continued apremilast after week 24 and 54 patients who switched to deucravacitinib) (table 1) — adjusted auc 0–52wk [% × weeks] was 2978.72 in the deucravacitinib arm and 1988.06 in the apremilast initiatiors arm — the adjusted difference in auc 0–52wk was 990.66 (95% ci, 683.37–1297.95); p < 0.001 — the benefit ratio of initiating with deucravacitinib vs apremilast was 1.50 • figure 2 displays the standardized adjusted cumulative auc for pasi 75 over 52 weeks spga 0/1 • standardized average cumulative spga 0/1 response over 52 weeks among patients initiating with deucravacitinib was 50.2% compared with 31.9% in patients initiating with apremilast (table 2) — adjusted auc 0–52wk [% × weeks] was 2612.82 in the deucravacitinib arm and 1657.13 in the apremilast initiators arm — the adjusted difference in auc 0–52wk was 955.69 (95% ci, 642.22–1269.16); p < 0.001 — the benefit ratio of initiating with deucravacitinib vs apremilast was 1.58 • figure 3 displays the standardized adjusted cumulative auc for spga 0/1 over 52 weeks table 1. cumulative clinical benefit measured by pasi 75 response over 52 weeks outcomes deucravacitinib, n = 332 apremilast initiators,a n = 168 difference in estimate (95% ci) p value benefit ratio adjusted auc 0–52wk , % × weeks 2978.72 1988.06 990.66 (683.37–1297.95) < 0.001 1.50 standardized average cumulative responseb 57.3% 38.2% — — aamong patients initiating with apremilast, 87 achieved pasi 50 at week 24 and continued receiving apremilast, and 54 did not achieve pasi 50 and switched to deucravacitinib. bauc 0–52wk /maximum auc 0–52wk . auc 0–52wk , area under the curve over 52 weeks; ci, confidence interval; pasi 75, 75% improvement from baseline in psoriasis area and severity index score. figure 2. standardized adjusted auc 0–52wk : pasi 75 0 10 20 30 40 50 60 st an d ar d iz e d a ve ra ge c u m u la ti ve r e sp o n se , % weeks 0 4 8 12 16 20 24 28 32 36 40 44 48 52 deucravacitinib (n = 332) apremilast initiators (n = 168)a aamong patients initiating with apremilast, 87 achieved pasi 50 at week 24 and continued receiving apremilast, and 54 did not achieve pasi 50 and switched to deucravacitinib. auc 0–52wk , area under the curve over 52 weeks; pasi 50/75, ≥50%/≥75% improvement from baseline in psoriasis area and severity index score. table 2. cumulative clinical benefit measured by spga 0/1 response over 52 weeks outcomes deucravacitinib, n = 332 apremilast initiators,a n = 168 difference in estimate (95% ci) p value benefit ratio adjusted auc 0–52wk , % × weeks 2612.82 1657.13 955.69 (642.22–1269.16) < 0.001 1.58 standardized average cumulative responseb 50.2% 31.9% — — aamong patients initiating with apremilast, 87 achieved pasi 50 at week 24 and continued receiving apremilast, and 54 did not achieve pasi 50 and switched to deucravacitinib. bauc 0–52wk /maximum auc 0–52wk . auc 0–52wk , area under the curve over 52 weeks; ci, confidence interval; spga 0/1, static physician global assessment score of 0 or 1. figure 3. standardized adjusted auc 0–52wk : spga 0/1 deucravacitinib (n = 332) apremilast initiators (n = 168)a 0 10 20 30 40 50 60 st an d ar d iz e d a ve ra ge c u m u la ti ve r e sp o n se , % weeks 0 4 8 12 16 20 24 28 32 36 40 44 48 52 aamong patients initiating with apremilast, 87 achieved pasi 50 at week 24 and continued receiving apremilast, and 54 did not achieve pasi 50 and switched to deucravacitinib. auc 0–52wk , area under the curve over 52 weeks; pasi 50, ≥50% improvement from baseline in psoriasis area and severity index score; spga, static physician global assessment score of 0 or 1. conclusions • initiating with deucravacitinib resulted in greater cumulative benefits over 52 weeks than initiating with apremilast — deucravacitinib initiators spend ≈150% more time in therapeutic response over 1 year compared with apremilast initiators • initiating with deucravacitinib as the first line rather than switching to deucravacitinib as the second line after failure to respond with apremilast may optimize the clinical benefit that patients receive references 1. armstrong aw, et al. j am acad dermatol. 2022;s0190-9622 [online ahead of print]. 2. armstrong aw, et al. [poster] presented at the american academy of dermatology annual meeting, march 25–29, 2022, boston, ma. 3. armstrong aw, et al. j dermatolog treat. 2017;28:200-205. 4. bushmakin ag, et al. qual life res. 2011;20:491-498. 5. warren rb, et al. j eur acad dermatol venereol. 2021;35:450-457. 6. blauvelt a, et al. j manag care spec pharm. 2021;27:84-94. acknowledgments • this study was supported by bristol myers squibb • medical writing and editorial assistance was provided by eleanor bush, ma, of peloton advantage, llc, an open health company, and funded by bristol myers squibb disclosures • awa: grants and personal fees: abbvie, bristol myers squibb, eli lilly, janssen, leo pharma, and novartis; personal fees: boehringer ingelheim/parexel, celgene, dermavant, genentech, glaxosmithkline, menlo therapeutics, merck, modernizing medicine, ortho dermatologics, pfizer, regeneron, sanofi genzyme, science 37, sun pharma, and valeant; grants: dermira, kyowa hakko kirin, and ucb, outside the submitted work • shp, vp, pn, mjc: employees of and may own stock options in bristol myers squibb • w-jw, vc: employees of open health, which has received consulting fees from bristol myers squibb 1 2 optimizing the treatment sequence: the cumulative clinical benefi t of treatment initiation with deucravacitinib versus apremilast over 52 weeks in patients with moderate to severe plaque psoriasis from the poetyk pso-1 trial april w. armstrong,1 sang hee park,2 viktor chirikov,3 pierre nicolas,2,4 wei-jhih wang,3 matthew j. colombo,2 vardhaman patel2 1keck school of medicine, university of southern california, los angeles, ca; 2bristol myers squibb, princeton, nj; 3open health, bethesda, md; 4bristol myers squibb, boudry, switzerland presented at the fall clinical dermatology conference; october 20—23, 2022; las vegas, nv this poster may not be reproduced without written permission from the authors.email for april armstrong, md, mph: aprilarmstrong@post.harvard.edu scientifi c content on demand to request a copy of this poster: scan qr code via a barcode reader application qr codes are valid for 30 days after congress presentation date synopsis • deucravacitinib is an oral, selective, allosteric tyrosine kinase 2 inhibitor approved by the us food and drug administration for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy • in the recent phase 3 clinical trial poetyk pso-1, patients with moderate to severe plaque psoriasis were randomized 2:1:1 to deucravacitinib, placebo, or apremilast1 — patients receiving apremilast who did not achieve at least 50% improvement from baseline in psoriasis area and severity index score (pasi 50) at week 24 crossed over to deucravacitinib1 • at week 52, 46.3% of these patients achieved at least 75% improvement from baseline in pasi score (pasi 75), and 42.6% achieved a static physician global assessment (spga) score of 0 or 1 (spga 0/1)2 — patients receiving apremilast who achieved pasi 50 at week 24 continued with apremilast — patients who received placebo are not represented in this analysis • this study evaluated the cumulative clinical benefit of initiating with deucravacitinib vs apremilast to determine the treatment pathway that provides greater benefit to the patient — the cumulative clinical benefit refl ects the total time patients spend in a state of therapeutic response3 • the results of this study indicate that initiating deucravacitinib as a first-line treatment offers greater benefits over time compared with initiating with apremilast objective • to evaluate the cumulative clinical benefit of initiating with deucravacitinib vs apremilast from baseline to week 52 based on data from poetyk pso-1 methods • poetyk pso-1 was a multicenter, randomized, double-blind, placeboand active comparator–controlled study1 — patients were aged ≥18 years and had moderate to severe plaque psoriasis (pasi score ≥12, spga score ≥3, and body surface area involvement ≥10%) — coprimary effi cacy endpoints were pasi 75 and spga 0/1 — nonresponder imputation was used for missing data • this post hoc analysis compared data from 2 arms in the poetyk pso-1 trial (figure 1) — deucravacitinib arm: patients initiated with and continued on deucravacitinib, regardless of response status — apremilast initiators arm: patients initiated with apremilast; at week 24, pasi 50 responders continued with apremilast while pasi 50 nonresponders crossed over to deucravacitinib • cumulative clinical benefit from randomization to week 52 was determined by the total area under the curve of clinical response over 52 weeks (auc 0–52wk ) in each arm — auc analysis has been employed to evaluate outcomes over time in clinical trials, as the auc refl ects the rapidity and durability, as well as the magnitude, of response3-6 • while assessments at discrete time points identify static responses, the auc approach captures cumulative treatment effects over time — this study determined the auc using data at a patient level (responder status at each time point over 52 weeks) • total auc 0–52wk was calculated separately for each efficacy endpoint, using the trapezoidal rule — total auc 0–52wk = 15i=0∑ (pi+pi+1)(ti+1−ti), where ti (i = 0, 1, 2, 3, …, 15) denotes the time points of weeks 0, 1, 2, 4, 8, 12, and 16, then every 4 weeks thereafter through week 52, and p i denotes the response (yes = 1; no = 0) at each time point, t i • the result was standardized as a percentage of maximum possible auc 0–52wk (0–5200 [% × weeks]) and aggregated to the population level • adjusted auc comparisons between the 2 treatment arms were based on an analysis of covariance (ancova) model, with the following stratification parameters: — prior use of a biologic treatment (yes/no) — region (united states, china, japan, rest of the world [row]) — body weight (<90 kg, ≥90 kg), in the united states and row only • ratios of auc 0–52wk were calculated, representing the relative cumulative clinical benefit of the 2 treatment pathways for achieving pasi 75 or spga 0/1 over the 52-week period figure 1. study design comparing data from 2 arms of poetyk pso-1 week 0 week 24 week 52 apremilast initiators arm (n = 168) deucravacitinib arm (n = 332) initiation of deucravacitinib continuation of deucravacitinib initiation of apremilast ≥pasi 50: continuation of apremilast <pasi 50: initiation of deucravacitinib pasi 50, 50% improvement from baseline in psoriasis area and severity index score. results pasi 75 • standardized average cumulative pasi 75 response over 52 weeks among patients initiating with deucravacitinib was 57.3% compared with 38.2% in patients initiating with apremilast (including 87 patients who continued apremilast after week 24 and 54 patients who switched to deucravacitinib) (table 1) — adjusted auc 0–52wk [% × weeks] was 2978.72 in the deucravacitinib arm and 1988.06 in the apremilast initiatiors arm — the adjusted difference in auc 0–52wk was 990.66 (95% ci, 683.37–1297.95); p < 0.001 — the benefit ratio of initiating with deucravacitinib vs apremilast was 1.50 • figure 2 displays the standardized adjusted cumulative auc for pasi 75 over 52 weeks spga 0/1 • standardized average cumulative spga 0/1 response over 52 weeks among patients initiating with deucravacitinib was 50.2% compared with 31.9% in patients initiating with apremilast (table 2) — adjusted auc 0–52wk [% × weeks] was 2612.82 in the deucravacitinib arm and 1657.13 in the apremilast initiators arm — the adjusted difference in auc 0–52wk was 955.69 (95% ci, 642.22–1269.16); p < 0.001 — the benefit ratio of initiating with deucravacitinib vs apremilast was 1.58 • figure 3 displays the standardized adjusted cumulative auc for spga 0/1 over 52 weeks table 1. cumulative clinical benefit measured by pasi 75 response over 52 weeks outcomes deucravacitinib, n = 332 apremilast initiators,a n = 168 difference in estimate (95% ci) p value benefit ratio adjusted auc 0–52wk , % × weeks 2978.72 1988.06 990.66 (683.37–1297.95) < 0.001 1.50 standardized average cumulative responseb 57.3% 38.2% — — aamong patients initiating with apremilast, 87 achieved pasi 50 at week 24 and continued receiving apremilast, and 54 did not achieve pasi 50 and switched to deucravacitinib. bauc 0–52wk /maximum auc 0–52wk . auc 0–52wk , area under the curve over 52 weeks; ci, confidence interval; pasi 75, 75% improvement from baseline in psoriasis area and severity index score. figure 2. standardized adjusted auc 0–52wk : pasi 75 0 10 20 30 40 50 60 st an d ar d iz e d a ve ra ge c u m u la ti ve r e sp o n se , % weeks 0 4 8 12 16 20 24 28 32 36 40 44 48 52 deucravacitinib (n = 332) apremilast initiators (n = 168)a aamong patients initiating with apremilast, 87 achieved pasi 50 at week 24 and continued receiving apremilast, and 54 did not achieve pasi 50 and switched to deucravacitinib. auc 0–52wk , area under the curve over 52 weeks; pasi 50/75, ≥50%/≥75% improvement from baseline in psoriasis area and severity index score. table 2. cumulative clinical benefit measured by spga 0/1 response over 52 weeks outcomes deucravacitinib, n = 332 apremilast initiators,a n = 168 difference in estimate (95% ci) p value benefit ratio adjusted auc 0–52wk , % × weeks 2612.82 1657.13 955.69 (642.22–1269.16) < 0.001 1.58 standardized average cumulative responseb 50.2% 31.9% — — aamong patients initiating with apremilast, 87 achieved pasi 50 at week 24 and continued receiving apremilast, and 54 did not achieve pasi 50 and switched to deucravacitinib. bauc 0–52wk /maximum auc 0–52wk . auc 0–52wk , area under the curve over 52 weeks; ci, confidence interval; spga 0/1, static physician global assessment score of 0 or 1. figure 3. standardized adjusted auc 0–52wk : spga 0/1 deucravacitinib (n = 332) apremilast initiators (n = 168)a 0 10 20 30 40 50 60 st an d ar d iz e d a ve ra ge c u m u la ti ve r e sp o n se , % weeks 0 4 8 12 16 20 24 28 32 36 40 44 48 52 aamong patients initiating with apremilast, 87 achieved pasi 50 at week 24 and continued receiving apremilast, and 54 did not achieve pasi 50 and switched to deucravacitinib. auc 0–52wk , area under the curve over 52 weeks; pasi 50, ≥50% improvement from baseline in psoriasis area and severity index score; spga, static physician global assessment score of 0 or 1. conclusions • initiating with deucravacitinib resulted in greater cumulative benefits over 52 weeks than initiating with apremilast — deucravacitinib initiators spend ≈150% more time in therapeutic response over 1 year compared with apremilast initiators • initiating with deucravacitinib as the first line rather than switching to deucravacitinib as the second line after failure to respond with apremilast may optimize the clinical benefit that patients receive references 1. armstrong aw, et al. j am acad dermatol. 2022;s0190-9622 [online ahead of print]. 2. armstrong aw, et al. [poster] presented at the american academy of dermatology annual meeting, march 25–29, 2022, boston, ma. 3. armstrong aw, et al. j dermatolog treat. 2017;28:200-205. 4. bushmakin ag, et al. qual life res. 2011;20:491-498. 5. warren rb, et al. j eur acad dermatol venereol. 2021;35:450-457. 6. blauvelt a, et al. j manag care spec pharm. 2021;27:84-94. acknowledgments • this study was supported by bristol myers squibb • medical writing and editorial assistance was provided by eleanor bush, ma, of peloton advantage, llc, an open health company, and funded by bristol myers squibb disclosures • awa: grants and personal fees: abbvie, bristol myers squibb, eli lilly, janssen, leo pharma, and novartis; personal fees: boehringer ingelheim/parexel, celgene, dermavant, genentech, glaxosmithkline, menlo therapeutics, merck, modernizing medicine, ortho dermatologics, pfizer, regeneron, sanofi genzyme, science 37, sun pharma, and valeant; grants: dermira, kyowa hakko kirin, and ucb, outside the submitted work • shp, vp, pn, mjc: employees of and may own stock options in bristol myers squibb • w-jw, vc: employees of open health, which has received consulting fees from bristol myers squibb 1 2 microsoft word july 2020 scom 789 proof returned.docx skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 389 short communications cyclosporine for severe drug eruption in a psoriasis patient sarina singer1, nahla shihab md2, mark lebwohl md3 1research assistant, icahn school of medicine at mount sinai, new york, ny 2clinical dermatology fellow, department of dermatology, icahn school of medicine at mount sinai, new york, ny 3professsor and chairman, department of dermatology, icahn school of medicine at mount sinai, new york, ny exanthematous drug eruptions, also known as morbilliform or maculopapular drug rashes, are the most common types of drug hypersensitivity reactions.1 they are believed to be driven by delayed-type, t cell-mediated type ivc reactions.2 eliciting drugs may induce the reaction directly or act as haptens. the most common culprits are antibiotics, including penicillins, cephalosporins, and sulfa drugs.3 the principal management of drug eruption is to withdraw the offending drugs and provide supportive care. for severe reactions, systemic corticosteroids are the most commonly used therapies. we herein report a case of a psoriasis patient with a severe exanthematous drug eruption that was successfully treated with short term of oral cyclosporine. a 75-year-old male presented to our department with a generalized exanthematous eruption two days after taking doxycycline for lyme disease. upon physical examination there were multiple erythematous macules and papules on face, trunk, and extremities. there were also multiple sharply demarcated erythematous scaly plaques on bilateral arms and legs. there was no fever, lymphadenopathy or hepatosplenomegaly. his body weight was 106 kg. his blood pressure, complete blood count, and chemistry screen were within normal limits. the patient had a history of psoriasis for which he was treated with topical corticosteroids as needed. we suspected that his new rash represented drug eruption, suggested discontinuation of doxycycline, and prescribed cyclosporine 250 mg by mouth twice a day. because guidelines and publications advise against use systemic corticosteroids in patients with psoriasis,4 we avoided oral prednisone to prevent exacerbation of psoriasis. the patient returned to the clinic one week after administration of cyclosporine with significant clearance of rash. the cyclosporine dose was then tapered down and discontinued within three weeks. the diagnosis of drug eruption is highly suspected in a patient with acute rash who recently receive a new systemic medication. diagnosis is made primarily by history taking and physical examination. laboratory introduction case presentation discussion skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 390 examination may be needed to exclude other diagnosis or involvement of systemic organ, in particular drug reaction with eosinophilia and systemic symptoms (dress). our patient came with a severe generalized exanthematous rash two days after taking oral doxycycline. he did not have fever, lymphadenopathy, or hepatosplenomegaly. his blood work was within normal limit. systemic corticosteroid is the most widely used treatment for severe drug eruption. however, in patient with psoriasis, systemic corticosteroid may cause disease deterioration after dose withdrawal.5 we chose oral cyclosporine for our patient because it is usually rapidly effective and has not been associated with rebound flares of psoriasis upon its discontinuation. the cyclosporine proved to be effective for both his drug eruption and psoriasis. cyclosporine is an immunomodulator drug that works by selectively inhibit calcineurin, resulting in impairment on the transcription of interleukin (il)-2, tumor necrosis factor (tnf)-alpha, il-3, il-4, and interferon (ifn)gamma.6 our patient began a 7-day course of oral cyclosporine at a dose of 5 mg/kg per day divided into twice daily dosing (250 mg twice daily). after one week of treatment, his eruption has significantly resolved. the cyclosporine dosage was then tapered gradually to 150 mg twice daily for one week and 100 mg twice daily for another week. the rapid and successful response in our patient suggests that cyclosporine could be a potential alternative treatment for severe drug eruption in patient with psoriasis or other condition where systemic corticosteroid is contraindicated. conflict of interest disclosures: none funding: none corresponding author: nahla shihab, md clinical dermatology fellow department of dermatology, mount sinai medical center, new york, ny 5 e 98th street, new york, ny, 10029 email: nahla.shihab@gmail.com references: 1. bigby m. rates of cutaneous reactions to drugs. arch dermatol 2001; 137:765. 2. lerch m, pichler wj. the immunological and clinical spectrum of delayed drug induced exanthems. curr opin allergy clin immunol 2004; 4:411. 3. bircher aj. exanthematous (maculopapular) drug eruption. [updated 2018 may 22]. in: uptodate [internet]. available from: https://www.uptodate.com/contents/exanthemato us-drug-eruption (accessed 11 november 2019). 4. menter a, korman nj, elmets ca, feldman sr, gelfand jm, gordon kb, gottlieb a, et al. guidelies of care for the management of psoriasis and psoriasis arthritis. j am acad dermatol. 2011 jul;65(1):137-74. 5. mrowietz u, domm s. systemic steroids in the treatment of psoriasis: what is fact, what is fiction. j eur acad dermatol venereol. 2013 aug;27(8):1022-5 6. hardinger k, magee cc. pharmacology of cyclosporine and tacrolimus. [updated 2018 april 25]. in: uptodate [internet]. available from: https://www.uptodate.com/contents/pharmacolog y-of-cyclosporine-and-tacrolimus (accessed 11 november 2019). skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 51 brief articles cutaneous scalp metastases from a left hallux subungual melanoma: an instructive case of scalp nodules llewelyn yi chang tan, mbchb1, chee hian tan, mbbs, mrcp, mmed1, joel hua liang lim mbbs, mrcp, mmed1 1national skin centre, singapore melanoma is the most aggressive form of skin cancer affecting patients worldwide and has the potential to metastasize to virtually any organ in the body. early detection is of paramount importance to minimize patient morbidity and mortality. however, there has been increasing evidence highlighting the existence of ethnic and geographical variations in the clinical presentation of melanomas. unlike the western population, the major subtype of melanoma affecting the asian population is in fact, acral lentiginous melanoma (alm) and not superficial spreading melanoma (ssm). we hereby present a case of left hallux subungual melanoma with scalp and probable hepatic metastases. a bedbound 87-year-old chinese woman with advanced parkinson’s disease was seen by the inpatient dermatology consult service for 2 asymptomatic scalp nodules, which have been present for a few years. according to her caregiver, the nodules were initially flat and resembled moles, but gradually enlarged over time. clinical examination revealed a 13mm hypermelanotic, infiltrated nodule on the right temporoparietal scalp and a 17mm ulcerated and sloughy, hyperpigmented nodule on the right paravertex (figure 1). a punch biopsy of the non-ulcerated scalp nodule was performed for histopathological assessment. this demonstrated an expanded dermis filled with nests and sheets of atypical epithelioid cells bearing moderate cellular and nuclear atypia with abstract melanoma is the most aggressive form of skin cancer affecting patients worldwide and has the potential to metastasize to virtually any organ in the body. early detection is of paramount importance to minimize patient morbidity and mortality. however, there has been increasing evidence highlighting the existence of ethnic and geographical variations in the clinical presentation of melanomas. unlike the western population, the major subtype of melanoma affecting the asian population is acral lentiginous melanoma (alm) and not superficial spreading melanoma (ssm). we hereby present a case of left hallux subungual melanoma with scalp and probable liver metastases. this case underscores the importance of examining the acral skin and nail apparatus for melanoma in asians and the need for increased public awareness regarding alms. introduction case presentation skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 52 figure 1. photo of the two hyperpigmented nodules on the patient’s scalp. prominent nucleoli, in conjunction with prominent mitotic figures. the atypical cells were strongly positive for melan-a and sox10 and negative for ae1/3 and ck5/6. this malignant proliferation extended beyond the inferior resection margin and did not involve the overlying epidermis indicating that the process was not cutaneous in origin and likely due to haematogenous dissemination (figure 2a, b, c). these findings were consistent with the diagnosis of metastatic melanoma. on further clinical examination, the patient was also found to have heterogeneous subungual hyperpigmentation over the left hallux (figure 3). dermoscopy showed variegated bluish-black linear pigmentation at the eponychium (cuticular region) extending to distal nail bed and a central intervening area of white regression. there was periungual hemorrhage but no hutchinson's sign (figure 4). this constellation of features was diagnostic for subungual melanoma. her chest x-ray was unremarkable. an ultrasound scan of the hepatobiliary system was ordered to investigate an elevated serum alkaline phosphatase level and it demonstrated small hypoand hyper-echoic foci in the liver as well as a large heterogeneous lesion in the right lobe. serum alpha fetoprotein levels were however normal. the diagnosis of left hallux subungual melanoma with scalp metastases and probable hepatic metastases was made figure 2. (a) the dermis is infiltrated with cohesive sheets and irregular nests of atypical cells abutting against, but without connection to the ulcerated epidermis (h&e, 10x). (b) the anaplastic cells, which are epithelioid in nature, exhibit nuclear and cellular atypia, with prominent atypical mitotic figures (h&e, 40x). (c) the anaplastic cells are positive for melan a. the bottom heavy positivity lends to the fact it is a dermal cutaneous metastasis. (melan a, 10x) skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 53 figure 3. photo of the subungual hyperpigmentation over the left hallux. given the patient’s age and poor premorbid status, her family opted for conservative management and declined further investigations. figure 4. close up photo of the subungual showing variegated bluish black linear pigmentation at the eponychium (cuticular region) extending to distal nail bed and a central intervening area of white regression in the setting of firm scalp nodules with minimal surface changes, an underlying malignancy needs to be ruled out. skin biopsy would be crucial to delineate if the nodules are primary cutaneous malignancies or cutaneous metastases from a distant primary malignancy, the latter would be more likely given the presentation of two discrete nodules. if this were a solitary lesion, a primary cutaneous malignancy (pcm) such as pigmented basal cell carcinoma would be more probable. other pcm like squamous cell carcinoma, angiosarcoma and merkel cell carcinoma are usually non-pigmented. numerous visceral cancers have been implicated in cutaneous metastasis, but a useful aide memoire are cancers arising from midline organs or those that are bilateral; namely thyroid, breast, lung, pancreatic, renal and ovarian carcinomas. lung carcinomas are also the most common primary malignancy in men while breast carcinomas are the most common in women. skin melanoma has also been reported to spread to the scalp1. melanoma results from an aberrant proliferation of melanocytes, which typically occurs on the skin but may rarely occur in the mouth, intestines or eyes. there are 4 major subtypes of cutaneous melanoma and they include superficial spreading melanoma (ssm), nodular melanoma (nm), lentigo maligna melanoma (lmm) and acral lentiginous melanoma (alm). from a histopathological perspective, the diagnosis of metastatic melanoma could be readily made. the presence of cohesive sheets and irregular nests of anaplastic cells without connection to the epidermis discussion skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 54 suggested a disseminated carcinoma, as opposed to a sarcoma or hematolymphoid neoplasm which are discohesive. aside from clinical correlation, delineating the cell type of the epithelioid carcinoma was done systemically via performing immunohistochemical stains. ae1/3 and ck5/6 negativity ruled out epithelial carcinomas originating from cells bearing high molecular weight cytokeratins (e.g. metastatic squamous cell carcinoma). positive melanocytic markers such as melan-a and sox-10 clinched the diagnosis of metastatic melanoma. sox-10 is a more sensitive stain for melanocytes as its a nuclear stain and was performed in this case should melan-a (a less sensitive cytoplasmic stain), return spuriously as a false negative.2 in western studies, ssm is the most common subtype followed by nm, lmn and lastly alm.3 alm in western countries only accounts for 2% to 3% of all cases of melanomas.4 however, this is converse in asians where alm is the commonest subtype. a 2019 retrospective study in the multi-ethnic country of singapore revealed that alm was the commonest subtype, accounting for 33% of all cases followed by ssm accounting for 24% of all cases.5 this is similar to other studies in other asian countries such as hong kong, japan and taiwan, where alm makes up roughly 50% of the total cases of melanoma.6-9 currently, there are no screening guidelines on melanoma for asian individuals. resources have instead been allocated in educating the general public regarding the increased incidence of alms in asians, the specific anatomical sites that it affects and the importance of early detection. fair skinned asians who develop hyperpigmentation over acral sites or melanonychia are advised to seek medical attention early so as to avoid the delay in diagnosis. these strategies to increase population based awareness have been effective in improving the survival rates for patients diagnosed with alms.9-10 when dealing with patients with a suspicious pigmented skin nodule, early referral to a dermatologist is warranted for consideration of biopsy so as to prevent delay in diagnosis. in the setting of multifocal pigmented skin nodules, cutaneous metastases has to be considered and investigating for a possible visceral primary malignancy is recommended. given the ease of migration across the world, it is imperative for clinicians to be aware of the ethnic and geographical difference in disease spectrum and have a low threshold for diagnostic biopsies to avoid late diagnosis with catastrophic sequelae. this case underscores the importance of examining the acral skin and nail apparatus for melanoma in asians and the need for increased public awareness regarding alms. conflict of interest disclosures: none funding: none corresponding author: llewelyn yi chang tan 1 mandalay road singapore 308205, singapore phone: +65-62534455 email: llewelyn.tan@mohh.com.sg references: 1. brownstein mh, helwig eb. metastatic tumor of the skin. cancer. 1972; 29(5):1298–1307. 2. tacha d, qi w, ra s, bremer r, yu c, chu j, hoang l, robbins b. a newly developed mouse monoclonal sox10 antibody is a highly sensitive and specific marker for malignant melanoma, including spindle cell and desmoplastic conclusion skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 55 melanomas. arch pathol lab med. 2015 apr;139(4):530-6. 3. jelfs pl, giles g, shugg d, coates m, durling g, fitzgerald p, et al. cutaneous malignant melanoma in australia, 1989. med j aust. 1994; 161(3):182-7. 4. bradford pt, goldstein am, mcmaster ml, tucker ma. acral lentiginous melanoma: incidence and survival patterns in the united states, 1986-2005. arch dermatol. 2009;145:427-34. 5. lim zv, tan wpm, chia hy, tan wdv, tan sh. a 20-year retrospective clinicopathologic study on melanoma in singapore. j am acad dermatol 2019;81:ab3. 6. nm luk, cl ho, cl choi, kh wong, kh yu, wk yeung. clinicopathological features and prognostic factors of cutaneous melanoma among hong kong chinese. clin exp dermatol. 2004;29(6):600-4. 7. chen yj, wu cy, chen jt, shen jl, chen cc, wang hc. clinicopathologic analysis of malignant melanoma in taiwan. j am acad dermatol. 1999;41(6):945-9. 8. lee hy, chay wy, tang mby, chio mtw, tan sh. melanoma: differences between asian and caucasian patients. ann acad med singapore. 2012;41(1):17-20. 9. hemmings de, johnson ds, tominaga gt, wong jh. cutaneous melanoma in a multiethnic population: is this a different disease?. arch surg. 2004;139(9):968-973. 10. kato t, suetake t, sugiyama y, et al. improvement in survival rate of patients with acral melanoma observed in the past 22 years in sendai, japan. clin exp dermatol. 1993;18(2):107-110. skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 534 original research an update on the global burden and socioeconomics of scabies: a cross-sectional analysis from the global burden of disease study 2017 katelyn urban, mpas1, rachel l. giesey, do2, maria delost, phd3, gregory r. delost, do1,4 1lake erie college of osteopathic medicine, greensburg, pa 2department of dermatology, university hospitals cleveland medical center, cleveland, ohio 3youngstown state university; youngstown, oh 4apex dermatology and skin surgery center; mayfield heights, oh common dermatoses represent a significant social impact worldwide with a few easilytreated disorders, such as scabies, disproportionately accounting for a greater amount of disability. scabies is a parasitic infection of the skin caused by the mite sarcoptes scabiei var. hominis. it is common worldwide, particularly in vulnerable populations including underprivileged societies, and institutional settings such as schools, nursing facilities, military camps, and prisons in resource-rich areas. abstract introduction: scabies represents a significant burden worldwide, but epidemiologically, relation to socioeconomic status, and impact of recent global interventions remains largely unknown. methods: we analyzed global scabies trends from 2015 to 2017 in 195 countries worldwide through the global burden of disease study (gbd) database, including age-standardized prevalence rates, relationship to comorbidities, and age and sex patterns. we also compared scabies burden to a country’s socioeconomic status by using disability-adjusted life years and socio-demographic index, respectively. results: the age-specific prevalence rate in 2017 demonstrated a right skewed distribution with a peak between 15 and 20 years of age, and a roughly equal male:female ratio across all ages. scabies burden was higher in resource-poor countries. the world regions of oceania, southeast asia, east asia, and tropical latin america had the greatest prevalence of scabies. the individual countries with highest scabies burden were papua new guinea (age-standardized dalys 148.2), solomon islands (140.5), kiribati (139.9), timor-leste (138.2) and the maldives (134.9). a positive linear relationship exists between scabies burden and burden of rheumatic fever and bacterial skin disease. conclusion: the burden of scabies is highest in children, adolescents, tropical climates, and lowincome countries. rheumatic fever and bacterial skin disease burden is higher in areas where scabies burden is also higher. these global data may potentially serve as a purposeful measure for directing resources to improve the global burden of scabies. introduction skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 535 one measure of scabies disease morbidity is through disability-adjusted life years (dalys), measured as years of life lost due to premature mortality in the population plus the years lost due to disability for people living with a health condition or its consequences.1 one daly can be thought of as one year of healthy life lost, and the sum of dalys across a population is the burden of disease.1 furthermore, the sociodemographic index (sdi) was developed in 2016 to track key measures of socioeconomic development, predict health outcomes, monitor inequalities, and monitor the impact of interventions on health outcomes such as dalys.2,3 the sdi is a composite average of income per capita, years of schooling, and total fertility rate (tfr) used to identify where countries score on a spectrum of development on a scale of zero to one.2 an sdi score of one represents the highest possible income per capita, greatest average number of years of schooling, and lowest tfr. metrics such as dalys and sdi may help dermatologists and key policy and decision makers interested in reducing global health disparities from scabies and its related comorbidities to focus their time and resources on interventions to help maximize public health impact. a recent study showed scabies caused 0.18% of all dalys in 2017, a decrease of 14% from the all global dalys in 2015.4,5 this decline is a promising sign of the impact of recent efforts, including the addition of scabies to the list of world health organization (who) tropical neglected diseases in 2017, the formation of the international alliance for the control of scabies in 2013, and the first consensus of a diagnostic criteria in 2018.6,7 the relationship of scabies burden to socioeconomic status along with the indirect disability associated with scabies is important to consider. infestation is frequently complicated by impetigo, cellulitis, and abscess due to streptococcus pyogenes and staphylococcus aureus.6 skin infection with s. pyogenes can also lead to the nonsuppurative complications of acute post-streptococcal glomerulonephritis and possibly acute rheumatic fever. populations with higher scabies prevalence have increased rates of acute post-streptococcal glomerulonephritis leading to end-stage renal disease due to scabies lesions secondarily infected by s. pyogenes. these populations have also been impacted by the high mortality rate of s. aureus bacteremia associated with crusted scabies.8 global mortality is likely underestimated and a theoretical algorithm to estimate scabiesrelated burden has been proposed.6 in this observational cross-sectional analysis study, we show multiple global epidemiological and socioeconomic trends in scabies in 195 countries worldwide using the most current data from the 2017 global burden of disease study (gbd) database. we include age and sex patterns, scabies burden through dalys, and provide comparisons to socioeconomic status. furthermore, we investigate the relationship of scabies burden to the burden of comorbidities from secondary bacterial skin infections. this study aims to contribute to the growing body of research addressing global trends in scabies, especially in recent years following some positive interventions, and its potential relationship with socioeconomic status through gbd data. our data was derived from publicly available gbd datasets from 2017. the gbd datasets provide data to compare the magnitude of diseases, injuries, and risk factors across methods skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 536 age groups, sexes, countries, regions, and time from 1990 to the present day for over 350 diseases in 195 countries.9 the gbd project is led by the institute for health metrics and evaluation (ihme) at the university of washington in collaboration with over 3,600 researchers and over 145 countries worldwide.9 an in-depth protocol is available from the ihme on data acquisition, and how it is incorporated, calculated, and published in the gbd study.10 we analyzed the annual percent change of scabies measured in dalys per 100,000 in all 195 countries worldwide between 1990 and 2017 to comprise a list of the countries with the greatest increase and decrease (table 1) in dalys. we provided age patterns by sex and the total number of prevalent cases and age-specific prevalence rates of scabies on a global level and by region in 2017 (figures 1 and 2). agestandardized scabies dalys per 100,000 were then compared to the absolute sdi values of all 195 gbd countries globally in 2017 (figure 3). statistical analysis of correlation between country wealth and scabies burden was performed using a twotailed correlation analysis (pearson’s r) of the 2017 gross domestic product (gdp) per capita data from the world bank and dalys (world bank). we estimated the burden of scabies compared to related comorbidities rheumatic fever and bacterial skin disease (figure 4). statistical analysis of correlation was again performed using a two-tailed correlation analysis using spss statistical software, version 25.0 (ibm corp., armonk, ny). the age-specific scabies prevalence rates in 2017 demonstrated a right skewed distribution with a peak between 15 and 20 table 1. top 5 countries with greatest annual average percent increase and greatest annual average percent decrease of scabies from 2015 to 2017, measured in dalys per 100,000. country average annual % change tanzania 0.87 estonia 0.81 united states 0.45 american samoa 0.36 ghana 0.28 fiji -3.35 united arab emirates -1.81 timor-leste -1.75 saudi arabia -1.53 the maldives -1.41 years of age, with roughly an equivalent number of males and females affected across all age groups (figure 1). in a regional comparison of scabies prevalence by sex, oceania ranked highest for both females (142 cases per 100,000) and males (146 cases per 100,000) (figure 2). southeast asia ranked second (124 cases per 100,000 for females and males) and east asia third (98 cases per 100,000 for females and males). western europe ranked lowest for both males and females (2 cases per 100,000). there does not appear to be a difference in prevalence between males and females in any particular region. a clustering of countries and regions with low sdi scores and high scabies dalys, and vice versa, is seen when comparing age-standardized dalys rates and sdi scores across all the countries surveyed by the gbd database in 2017 (figure 3). additionally, a moderate negative correlation results skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 537 figure 1: age patterns by sex in 2017 of the total number of prevalent cases and age-specific prevalence rate of scabies at the global level. (-0.58) was found between gdp per capita and scabies dalys. the top five individual countries with the highest age-standardized daly rates overall were papua new guinea (age-standardized dalys 148.2), solomon islands (140.5), kiribati (139.9), timor-leste (138.2) and the maldives (134.9). the countries with the greatest annual increase in dalys from 2015 to 2017 include tanzania (0.87), estonia (0.81), united states (0.45), american samoa (0.36), and ghana (0.28). the countries with the greatest annual decrease in dalys include fiji (-3.35), united arab emirates (1.81), timor-leste (-1.75), saudi arabia (1.53), and the maldives (-1.41). when comparing scabies daly rates and scabies comorbidity daly rates across all 195 gbd countries in 2017, a positive linear relationship is seen with both rheumatic fever (r = 0.55) and bacterial skin disease (r = 0.46), both statistically significant at p<0.05 (figure 4). scabies prevalence was highest among younger individuals, with a peak between 15 and 20 years of age. geographically, scabies prevalence was highest in warmer, tropical climates. there was not a difference in prevalence between genders by age or regional comparisons. our data also suggests that as country wealth decreases, scabies burden also increases. this concurs with previous studies demonstrating that overcrowding in hot tropical climates facilitates the rapid spread of the scabies mite. low socioeconomic status can further discussion skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 538 figure 2: age-standardized prevalence of scabies by sex and geographical region in 2017. worsen disease burden for patients with scabies attributable to a lack of access to healthcare in general, specialty care, and absence of public education, all of which may contribute to a deficiency in timely and definitive management.11 our results demonstrate a positive linear relationship between scabies burden and burden of rheumatic fever and bacterial skin infections. it is well documented that scabies infestation provides a portal of entry for bacteria, which supports our findings of higher burden of bacterial skin diseases in countries with higher burden of scabies. a previous study also demonstrated high rates of rheumatic heart disease in countries with high rates of scabies and impetigo, but low rates of streptococcal pharyngitis.12 confounding factors such as decreased access to healthcare, and thus antibiotic treatment may be considered in the development of rheumatic heart disease. however, a longitudinal study with an analysis adjusted for socio-economic status demonstrated that children aged 3 through 12 presenting for their first dental visit in auckland, new zealand with a diagnosis of scabies after enrollment had a 9-fold increase in acute rheumatic fever or chronic rheumatic heart disease compared to those without a scabies diagnosis.13 our results indicate a higher burden of rheumatic heart disease in those geographic areas of higher scabies burden, possibly attributable to skin co-infection with s. pyogenes, but this skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 539 figure 3: age-standardized dalys rates from scabies by socio-demographic index (sdi) for 195 countries and territories in 2017. skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 540 figure 4: scabies comorbidity daly rates for rheumatic fever and bacterial skin disease, measured in dalys per 100,000 relationship requires further examination. the global contribution of scabies to dalys from all diseases decreased from 0.21% in 2015 to 0.18% in 2017. timor-leste ranked third and fiji fifth in 2015 for greatest scabies burden; both are in the top 5 countries with the greatest annual decline in scabies burden from 2015 to 2017. this data suggests that interventions currently underway in areas of high need are producing a positive impact. perhaps the most impactful intervention has been the implementation of mass drug administration (mda) in community-wide settings. in the shift randomized trial, conducted in fiji, ivermectin-based mda reduced the prevalence of scabies by 94% at 12 months with sustained reductions demonstrated at 24 months.14 limitations of the gbd studies have been described, including inconsistent reporting of mortality by skin disease in assessing dalys.11 disability only reflects a) symptoms such as itch and b) appearance including disfigurement, not capturing other complications such as secondary infection, skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 541 mental illness, etc. additionally, the scabies burden estimates by the gbd only account for direct effects of scabies, not secondary complications such as bacterial infections, glomerulonephritis, and rheumatic fever. although we also analyzed the burden estimates of rheumatic fever and bacterial skin diseases as they relate to scabies across all countries, there are confounding causes for these entities apart from scabies such as streptococcal pharyngitis. regardless of these limitations, understanding the relationship between epidemiological factors, secondary complications, and socioeconomic status on geographical burden scabies is a valuable step in developing measurable, impactful, and sustainable interventions to reduce disease morbidity in both resource-rich and resource-poor countries. despite recent improvements, scabies continues to contribute to needless global suffering due to incorrect or delayed diagnosis, inadequate treatment, insufficient access to care, secondary complications, and social stigmatization. dermatologists continue to face the challenge of raising global awareness and treating scabies to improve health care outcomes, quality of life and social inclusion. lessons of success can be gleaned from countries with decreasing daly rates, such as fiji, and areas for improvement can be highlighted by countries with increasing daly rates. increased outreach, funding, collaboration, and development of new therapies are promising steps to overcome this challenge and reduce the global burden of scabies. abbreviations and acronyms: disability adjusted life years (dalys) global burden of disease study (gbd) institute for health metrics and evaluation (ihme) mass drug administration (mda) socio-demographic index (sdi) total fertility rate (tfr) world health organization (who) conflict of interest disclosures: none funding: this research has been conducted as part of the global burden of diseases, injuries, and risk factors study (gbd), coordinated by the institute for health metrics and evaluation. the gbd was partially funded by the bill & melinda gates foundation; the funders had no role in the study design, data analysis, data interpretation, or writing of the report. the lead author is a collaborator with the global burden of disease. this article was not developed with consultation or support with the global burden of disease research team. the work has not been previously presented. corresponding author: rachel giesey, do 11100 euclid avenue cleveland, oh 44106 phone: 330-592-6091 email: rachel.giesey2@uhhospitals.org references: 1. metrics: disability-adjusted life year (daly). world health organization. https://www.who.int/healthinfo/global_burden_dis ease/metrics_daly/en/. accessed june 22, 2020. 2. frequently asked questions. ihme. http://www.healthdata.org/gbd/faq. accessed june 22, 2020. 3. leach-kemon k. a new way of measuring development helps assess health system performance. ihme. http://www.healthdata.org/acting-data/new-waymeasuring-development-helps-assess-healthsystem-performance. published 2017. accessed june 22, 2020. 4. karimkhani c, colombara dv, drucker am, et al. the global burden of scabies: a cross-sectional analysis from the global burden of disease study 2015. the lancet. 2017;17(12):1247-1254. 5. mehrmal s, uppal p, giesey r, delost g. identifying the prevalence and disability-adjusted life years of the most common dermatoses conclusion skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 542 worldwide. j am acad dermatol. 2020;82(1):258259. 6. engelman d, kiang k, chosidow o, et al. toward the global control of human scabies: introducing the international alliance for the control of scabies. plos negl trop dis. 2013;7(8):e2167. 7. engelman d, fuller lc, steer ac. consensus criteria for the diagnosis of scabies: a delphi study of international experts. plos negl trop dis. 2018;12(5):e0006549. 8. thomas c, coates sj, engelman d, chosidow o, chang ay. ectoparasites: scabies. j am acad dermatol. 2020 mar;82(3):533-548. 9. frequently asked questions. ihme. http://www.healthdata.org/gbd/faq. accessed june 22, 2020. 10. protocol for the global burden of diseases, injuries, and risk factors study (gbd). in: institute for health metrics and evaluation; 2018. 11. seth d, cheldize k, brown d, freeman ef. global burden of skin disease: inequities and innovations. curr dermatol rep. 2017;6(3):204210. 12. parks t, smeesters pr, steer ac. streptococcal skin infection and rheumatic heart disease. curr opin infect dis. 2012;25(2):145-153. 13. thornley s, marshall r, jarrett p, sundborn g, reynolds e, schofield g. scabies is strongly associated with acute rheumatic fever in a cohort study of auckland children. j paediatr child health. 2018 jun;54(6):625-632 14. romani l, whitfeld mj, koroivueta j, et al. mass drug administration for scabies 2 years of follow-up. n engl j med. 2019;381(2):186-187. microsoft word penile mondor.doc skin july 2017 volume i issue i copyright 2017 the national society for cutaneous medicine 52 brief articles penile mondor's disease: two rare cases samuel p. haslam, baa chinelo ikpeama, md, mbab michael g. wilkerson, mdb aschool of medicine, bdepartment of dermatology, university of texas medical branch, galveston, tx penile mondor's disease (pmd) is a subset of mondor's disease, which is a superficial thrombophlebitis of the chest wall or breast in women. in pmd, the dorsal vein of the penis is affected. the average patient is a twenty to forty year old male who presents with a firm, cord-like lesion on the dorsum of the penis 24 to 48 hours after prolonged sexual activity1. the lesion may be painful or painless, and the pain is often exacerbated by exertion. ultrasound is necessary to confirm the diagnosis, showing occlusion of the dorsal vein. treatment is supportive with complete resolution in one to two months. a 55-year-old male with no past medical history presented with the complaint of a five day history of a firm, painful area on the dorsal shaft of penis. he described a history of prolonged sexual activity before the painful area developed. physical exam was significant for an indurated, pinkcolored, palpable cord on the dorsolateral shaft of the penis (figure 1). ultrasound of the cord demonstrated isogeneity of the area (figure 2). since no large or complex cystic structures were identified to suggest sclerosing lympangitis, the diagnosis of penile mondor's disease (pmd) was made. the patient was advised to take ibuprofen as needed for pain and to apply warm, wet compresses three times per day. the patient followed treatment recommendations and his lesion resolved. similarly, a 27-year-old male complained of a one month history of a painful bump on the dorsal shaft of his penis. he reported a history of frequent and prolonged sexual intercourse before the area developed, and he stated that sexual intercourse exacerbated the pain. physical exam revealed a firm, brown, painful palpable cord over the dorsum of the penile shaft (figure 3). pmd was again suspected, and the patient was advised to abstain from sexual activity until the pain and elevated area resolved. he was also encouraged to use warm compresses and anti-inflammatories to control the pain. ultrasound was suggested to confirm the diagnosis of pmd, but the patient did not follow-up for imaging studies. introduction case descriptions skin july 2017 volume i issue i copyright 2017 the national society for cutaneous medicine 53 figure 1: pmd, case 1. circled is the palpable cord. figure 2: pmd, case 1 ultrasound. figures figure 3: pmd, case 2. circled is the palpable cord. skin july 2017 volume i issue i copyright 2017 the national society for cutaneous medicine 54 both patients were diagnosed with penile mondor's disease (pmd), which is a superficial thrombophlebitis of the dorsal vein of the penis. pmd is a rare variant of classic mondor's disease, which is a more common superficial thromblophlebitis that occurs on the chest wall or breast in women. the most common cause of pmd is trauma due to due to frequent and prolonged sexual intercourse2, but other risk factors include infections, surgery, cancer, and virchow's triad of endothelial damage, venous stasis, and hypercoagulable state3. the typical pmd patient is a twenty to forty year old male who presents with a firm, cordlike lesion on the dorsum of the penis 24 to 48 hours after prolonged sexual activity. the thrombosed vessel is often adherent to the overlying skin, and the area of thrombosis may extend to the suprapubic region1. patients may complain of continuous or throbbing pain and pain exacerbated by erection and sexual activity. color doppler ultrasound confirms the diagnosis of pmd by showing occlusion of the dorsal vein and absent flow signals. color doppler ultrasound also differentiates pmd from sclerosing lymphangitis and peyronie's disease; both diseases are in the differential for this type of presentation1. sclerosing lympangitis is more common than pmd and is characterized by thrombosis of the lymphatic vessels. thrombosed and dilated lymphatic vessels and preserved flow in the dorsal vein are seen on ultrasound4. clinically, sclerosing lympangitis may appear similar to pmd, but lack of pain is more frequent5. peyronie's disease is a connective tissue disease that is characterized by fibrous plaques in the tunica albuginea on ultrasound and pain and abnormal curvature on clinical exam. pmd is a relatively benign disease, and symptoms usually resolve within four to six weeks. patients typically regain full vessel permeability in nine weeks with or without medical treatment1. patients are advised to use anti-inflammatory agents and to restrict sexual activity to reduce pain and promote resorption of the thrombosis. after six weeks, patients who are symptomatic and have loss of flow on color doppler ultrasound are considered to be refractory to treatment. these patients may be topically treated with heparin creams. thrombectomy and resection of the superficial penile vein may be performed if the thrombosis fails to resolve. most importantly, early diagnosis and reassurance of the relatively benign nature of the disease helps reduce patient anxiety and concerns over sexual dysfunction. follow-up to ensure that the thrombosis resolves is warranted. currently, further work-up for an underlying hypercoagulable state is not advised. conflict of interest disclosures: none funding sources: none references: 1. öztürk h. penile mondor’s disease. basic and clinical andrology. 2014;24:5. 2. kumar b. penile mondor’s disease: an underdiagnosed and under-reported benign condition. sex transm infect. 2013;89:a127–a128. 3. griger dt, angelo te, grisier db. penile mondor’s disease in a 22-year-old man. j am osteopath assoc. 2001;101(4):235–237. 4. han hy, chung dj, kim kw, hwang cm. pulsed and color doppler sonographic findings of penile mondor’s disease. korean j radiol. 2008;9:179–181. 5. yap fb. nonvenereal sclerosing lymphangitis of the penis. southern medical journal. 2009;102(12):1269-71. discussion results figure 1. patient flow til, tildrakizumab. • the patient flow from randomization through the extension study for resurface 1 and resurface 2 is shown in figure 1 table 1. baseline demographics for patients entering extension resurface 1 resurface 2 til 100 mg (n = 239) til 200 mg (n = 267) til 100 mg (n = 382) til 200 mg (n = 349) sex, male, n (%) 159 (66.5) 183 (68.5) 291 (76.2) 242 (69.3) age, mean ± sd, years 46.9 ± 13.0 47.1 ± 13.0 44.2 ± 13.2 45.6 ± 12.8 race, white, n (%) 163 (68.2) 173 (64.8) 352 (92.1) 329 (94.3) baseline pasi score, mean ± sd 20 ± 7.6 21.3 ± 9.6 19.8 ± 7.6 19.3 ± 6.9 weight, mean ± sd, kg 87.1 ± 24.4 87.8 ± 24.2 88.4 ± 21.4 89.0 ± 21.5 body surface area, mean ± sd 30.2 ± 17.5 31.7 ± 19.6 32.6 ± 18.0 30.1 ± 15.8 pasi, psoriasis area and severity index; sd, standard deviation; til, tildrakizumab. • the efficacy analysis was concluded at week 208 for resurface 1 (extension week 144; 2210.8 total patient years) and week 196 for resurface 2 (2768.3 total patient years) efficacy figure 2. resurface 1 week 64 results of pasi 75/90/100 responses for a) tildrakizumab 100 mg, b) tildrakizumab 200 mg, and c) pga response; and resurface 2 week 52 results of pasi 75/90/100 responses for d) tildrakizumab 100 mg, e) tildrakizumab 200 mg, and f) pga response a) b) c) d) e) f) pasi, psoriasis area and severity index; pga, physician’s global assessment; til, tildrakizumab. • the proportion of patients achieving pasi 75/90/100 responses and pga responses (“clear” or “minimal” with a >2-grade reduction from baseline) during the base study period of 64 weeks (resurface 1) or 52 weeks (resurface 2) are shown in figure 2 figure 3. pasi 75/90/100 responses during the extension study period by tildrakizumab dose in a) resurface 1, and b) resurface 2 a) b) fas population; missing data at a given visit were not imputed. n = number of patients with data at each visit. fas, full analysis set; pasi, psoriasis area and severity index; til, tildrakizumab. figure 4. pga responses of ‘clear’ or ‘minimal’ with a grade ≥2 reduction from baseline during extension study period by dose in a) resurface 1 and b) resurface 2 a) b) fas population; missing data at a given visit were not imputed. n = number of patients with data at each visit. fas, full analysis set; pga, physician’s global assessment; til, tildrakizumab. • the proportions of patients who achieved a pga response during the extension study period in resurface 1 and resurface 2 are presented in figure 4 introduction • tildrakizumab is a high-affinity, humanized, immunoglobin g1κ, anti–interleukin-23p19 monoclonal antibody approved for the treatment of moderate to severe plaque psoriasis • two large, phase 3, randomized, controlled trials (resurface 1, nct01722331; and resurface 2, nct01729754) of tildrakizumab were conducted in patients with moderate to severe chronic plaque psoriasis1 — tildrakizumab significantly improved psoriasis response rates vs placebo measured with the psoriasis area and severity index (pasi 75, pasi 90, and pasi 100) and physician’s global assessment (pga) score, by week 12 (primary endpoint) — tildrakizumab was well tolerated with low frequencies of serious adverse events (aes) and discontinuations due to aes2 objectives • to evaluate the 4-year efficacy data for tildrakizumab in the ongoing long-term extension period of the phase 3 resurface 1 and resurface 2 studies • to evaluate the 4-year safety data for the base and extension periods of resurface 1 and resurface 2 methods base study • participants ≥18 years of age with moderate to severe chronic plaque psoriasis (body surface area involvement ≥10%, pga score ≥3, and pasi score ≥12) were eligible • part 1 (weeks 1–12). patients were randomized (1:2:2) to blinded subcutaneous placebo or tildrakizumab 100 or 200 mg at weeks 0 and 4. resurface 2 also contained an etanercept arm (50 mg twice a week) • part 2 (weeks 12–28). patients previously receiving placebo were rerandomized to tildrakizumab 100 or 200 mg at weeks 12 and 16 and every 12 weeks (q12w) thereafter. patients continuing tildrakizumab from part 1 received a placebo injection at week 12 to maintain the blind and a dose of tildrakizumab at weeks 16 and 28. patients previously receiving etanercept 50 mg twice a week in resurface 2 continued etanercept once a week. at week 28, tildrakizumab nonresponders (pasi <50) and etanercept responders discontinued • part 3 (weeks 28–64/52). tildrakizumab responders (pasi ≥75) were rerandomized to receive placebo every 2 weeks (resurface 1) or tildrakizumab 100 or 200 mg q12w (resurface 1 and 2). responders who were rerandomized to placebo were retreated with the same tildrakizumab dose upon relapse (defined as reduction in maximum pasi response by 50%). in resurface 2, etanercept partial responders (pasi ≥50 and pasi <75) or nonresponders transitioned to tildrakizumab 200 mg • resurface 1 base study was 64 weeks; resurface 2 base study was 52 weeks extension study • patients who completed the base study with pasi ≥50 and received tildrakizumab within 12 weeks of base study end could enter a long-term, open-label extension study (up to 192 weeks) • in the extension study (resurface 1: weeks 64–256; resurface 2: weeks 52–240), patients received the same dose of tildrakizumab as at completion of base study efficacy and safety • efficacy was evaluated using pasi and pga response for all patients who received ≥1 dose during the extension study (full analysis set [fas] population) with no imputation of missing data (up to 4 years) • safety: aes were evaluated for all patients who received ≥1 dose during the base or extension study (up to 5 years) — cumulative and yearly ae incidence rates calculated using base and extension study data — discontinuation rates analyzed for fas population efficacy and safety of long-term tildrakizumab for plaque psoriasis: 4-year results from resurface 1 and resurface 2 richard g langley,1 jeffrey crowley,2 melinda gooderham,3 kim a papp,4 neil j korman,5 lynda spelman,6 atsuyuki igarashi,7 mamitaro ohtsuki,8 aditya k gupta,9 paul yamauchi,10 jeffrey parno,11 alan m mendelsohn,11 stephen j rozzo,11 kimberly eads,12 scott guenthner,12 m alan menter13 1division of dermatology, department of medicine, dalhousie university, halifax, ns, canada; 2bakersfield dermatology & skin cancer medical group, bakersfield, ca, usa; 3probity medical research, and skin centre for dermatology, peterborough, on, canada; and queen’s university, kingston, on, canada; 4k. papp clinical research and probity medical research, waterloo, on, canada; 5case western reserve university and university hospital cleveland center, cleveland, oh, usa; 6veracity clinical research, woolloongabba, brisbane, queensland, australia; and probity medical research, brisbane, australia; 7department of dermatology, ntt medical center tokyo, tokyo, japan; 8department of dermatology, jichi medical university hospital, tochigi-ken, japan; 9division of dermatology, department of medicine, university of toronto school of medicine, toronto, canada; and mediprobe research inc., london, canada; 10david geffen school of medicine at university of california los angeles, los angeles, ca, usa; 11sun pharmaceutical industries, inc., princeton, nj, usa; 12the indiana clinical trials center, plainfield, in, usa; 13division of dermatology, baylor scott & white, and texas a&m college of medicine, dallas, tx, usa safety • of the 506 patients who entered the extension period in resurface 1, a total of 113 (22%) discontinued. in resurface 2, a total of 153 (20.9%) of 731 patients discontinued — most common causes of discontinuation were patient withdrawal (resurface 1: 8%; resurface 2: 7.5%), aes (resurface 1: 5%; resurface 2: 3.0%), and loss to follow-up (resurface 1: 4%; resurface 2: 2.9%) • the cumulative numbers of patients who reported prespecified aes after up to 5 years of tildrakizumab treatment are shown in table 2 • in resurface 1, there were 2 deaths among patients who proceeded from the base study to the long-term extension: 1 patient receiving tildrakizumab 100 mg (metastatic carcinoma of the bladder with intracranial hemorrhage) and 1 patient receiving tildrakizumab 200 mg (suicide) • in resurface 2, there were 4 deaths among patients who proceeded into the extension: 3 patients receiving tildrakizumab 100 mg and 1 patient receiving tildrakizumab 200 mg table 2. cumulative number of patients with aes of interest after up to 5 years of treatment aes, na (exposure-adjusted rate)b resurface 1 resurface 2 til 100 mg (n = 383; 1410.4 py) til 200 mg (n = 399; 1606.5 py) til 100 mg (n = 410; 1513.3 py) til 200 mg (n = 380; 1404.7 py) etnc (n = 313; 153.4 py) severe infections 13 (0.9) 17 (1.1) 17 (1.6) 14 (1.0) 3 (2.0) malignancies 18 (1.3) 11 (0.7) 10 (0.9) 12 (0.9) 4 (2.6) nonmelanoma skin cancer 6 (0.4) 5 (0.3) 3 (0.3) 5 (0.4) 2 (1.3) melanoma skin cancer 1 (0.1) 1 (0.1) 1 (0.1) 1 (0.1) 0 confirmed extended mace 7 (0.5) 9 (0.6) 7 (0.7) 10 (0.7) 1 (0.7) drug-related hypersensitivity reactions 2 (0.1) 1 (0.1) 2 (0.2) 3 (0.2) 0 death 1 (0.1) 2 (0.1) 6 (0.6) 1 (0.1) 0 aincludes patients who received til 100 or 200 mg at any time during the study. bnumbers in parentheses represent the number of patients with the event per 100 py of exposure unless otherwise noted. cetanercept exposure only occurred during parts 1 and 2, there was no exposure after week 28. ae, adverse event; etn, etanercept; mace, major adverse cardiovascular event; py, patient-year; til, tildrakizumab. conclusions • over 4 years of treatment with tildrakizumab, pasi and pga response rates were high and durable for the tildrakizumab 100 and 200 mg doses in both resurface 1 and resurface 2 • through up to 5 years of follow-up, both tildrakizumab doses were well tolerated with low rates of aes of interest reported with long-term treatment in both resurface 1 and resurface 2. ae rates were comparable relative to etanercept-treated patients in resurface 2 references 1) reich k, et al. lancet. 2017;390:276–88; 2) blauvelt a, et al. br j dermatol. 2018;179:615–22. acknowledgments we thank the patients for their participation. the study was funded by merck sharp & dohme corp., a subsidiary of merck & co., inc., kenilworth, nj, usa. analyses were funded by sun pharmaceutical industries, inc., princeton, nj, usa. medical writing support was provided by kathleen pieper, phd, of alphabiocom, llc, and funded by sun pharmaceutical industries, inc. disclosures rgl has served as principal investigator for and is on the scientific advisory board or served as a speaker for abbvie; amgen; boehringer ingelheim; celgene; eli lilly and co.; janssen; leo pharma; merck & co; novartis; pfizer; and sun pharmaceutical industries, inc. jc has received research/grant support from abbvie; amgen; boehringer ingelheim; eli lilly and co.; janssen; mc2 therapeutics; merck & co.; novartis; pfizer; regeneron; sandoz; sanofi; sun pharmaceutical industries, inc.; ucb; and verrica pharmaceuticals; has served as consultant for abbvie; amgen; celgene; dermira; eli lilly and co.; novartis; sun pharmaceutical industries, inc.; and ucb; and has worked on speakers bureau for abbvie, janssen, eli lilly and co., novartis, regeneron, sanofi, and ucb. mg has been an investigator, consultant, and/or speaker for abbvie; actelion pharmaceuticals; akros pharma; amgen; arcutis pharmaceuticals; boehringer ingelheim; bristol-myers squibb; celgene; dermira; eli lilly and co.; galderma; glenmark; glaxosmithkline; janssen; leo pharma; medimmune; merck & co; novartis; pfizer; regeneron; roche; sanofi genzyme; sun pharmaceutical industries, inc.; ucb; and valeant pharmaceuticals; and has been on an advisory board for abbvie; amgen; boehringer ingelheim; celgene; eli lilly and co.; galderma; janssen; leo pharma; novartis; pfizer; regeneron; sanofi genzyme; sun pharmaceutical industries, inc.; and valeant pharmaceuticals. kap has served as consultant and/or investigator and/or speaker for abbvie, akros, allergan, amgen, anacor, arcutis, astellas, astrazeneca, baxalta, baxter, boehringer ingelheim, bristol-myers squibb, canfite, celgene, coherus, dermira, dow pharma, eli lilly and co., forward pharma, galderma, genentech, gilead sciences, glaxosmithkline, inflarx gmbh, janssen, kyowa hakko kirin, leo pharma, medimmune, meiji seika pharma, merck sharp & dohme, merck-serono, mitsubishi pharma, moberg pharma, novartis, pfizer, prcl research, regeneron, roche, sanofi-aventis/genzyme, takeda, ucb, and valeant/bausch health; on a steering committee and/or advisory board for abbvie, amgen, astellas, baxter, boehringer ingelheim, bristol-myers squibb, celgene, dow pharma, eli lilly and co., galderma, janssen, kyowa hakko kirin, merck sharp & dohme, merck-serono, novartis, pfizer, regeneron, sanofi-aventis/genzyme, ucb, and valeant/bausch health; and as scientific officer for akros, anacor, and kyowa hakko kirin. njk has received grants/research funding via their institution from eli lilly and co., leo pharma, merck sharp & dohme, pfizer, prothena, trevi, and ucb pharma; honoraria as an advisory board member for abbvie; celgene; eli lilly and co.; genentech; glaxosmithkline; immune pharm; janssen; novartis; regeneron; sun pharmaceutical industries, inc.; and valeant; and honoraria as a speaker for abbvie, eli lilly and co., janssen, and novartis. ls has served on advisory boards for abbvie, eli lilly and co., galderma, and novartis; has served as an investigator for abbvie; amgen; anacor; ascend biopharmaceuticals; astellas; australian wool innovation limited; blaze bioscience; bms; celgene; dermira; eli lilly and co.; galderma; genentech; glaxosmithkline; janssen; kythera; leo pharma; merck; novartis; phosphagenics; regeneron; sun pharmaceutical industries, inc.; and trius; and has received sponsored travel from abbott labs, janssen-cilag, and novartis. ai has received honoraria as a member of an advisory board for abbvie, celgene k.k., eli lilly japan k.k., janssen pharmaceutical k.k., maruho co ltd., novartis pharma k.k., and sun pharma japan ltd. mo has received honoraria as a member of an advisory board for abbvie, boehringer ingelheim co ltd, bristol-myers squibb company, celgene k.k., eisai co ltd, eli lilly japan k.k., janssen pharmaceutical k.k., kyowa hakko kirin co ltd, leo pharma k.k., maruho co ltd., mitsubishi tanabe pharma co, novartis pharma k.k., pfizer japan, and sun pharma japan ltd. akg has been an investigator for sun pharmaceutical industries, inc. py has received honoraria as a consultant from abbvie; amgen; celgene; janssen; leo pharma; menlo therapeutics; novartis; ortho dermatologics; pfizer; regeneron; and sun pharmaceutical industries, inc.; research grants from amgen, celgene, dermira, galderma, janssen, leo pharma, lilly icos, medimmune, menlo therapeutics, novartis, ortho dermatologics, pfizer, regeneron, and sandoz; has served on advisory boards for amgen, dermira, and lilly icos; and has served as a speaker for abbvie; amgen; celgene; janssen; leo pharma; lilly icos; novartis; ortho dermatologics; pfizer; regeneron; sanofi/regeneron; and sun pharmaceutical industries, inc. amm is an employee of sun pharmaceutical industries, inc.; and has individual shares in johnson and johnson, and as part of a retirement account/mutual funds. sjr is an employee of sun pharmaceutical industries, inc. ke has nothing to disclose. sg has received grants and/or honoraria as an investigator and/or speaker from abbvie; amgen; dermira; eli lilly and co.; encore dermatology; genentech; janssen; leo pharma; pfizer; sun pharmaceutical industries, inc.; ucb; and vanda. mam has received grants and/or honoraria as a consultant, investigator, and/or speaker for abbvie, abbott labs, amgen, anacor, boehringer ingelheim, celgene, eli lilly and co., janssen, leo pharma, merck & co, novartis, sienna, and ucb; and has been on an advisory board for abbvie, amgen, boehringer ingelheim, eli lilly and co., janssen, leo pharma, and sienna. randomized base study extension study completed week 64/52 entered extension completed extension week 208/196 n = 772 n = 1090 n = 341 n = 362 n = 267 n = 349 n = 226 n = 28 n = 239 n = 382 n = 178 n = 29 n = 297 n = 394 resurface 1 resurface 2 til 100 mg til 200 mg presented at fall clinical dermatology conference for pas & nps 2020, april 3–5, orlando, fl, usa pasi 75 pasi 90 pasi 100 0 20 40 60 80 100 resurface 2 til 100 mg p at ie nt s , % pasi 75 pasi 90 pasi 100 0 20 40 60 80 100 resurface 2 til 200 mg p at ie nt s , % til 100 mg til 200 mg 0 20 40 60 80 100 resurface 2 pga p at ie nt s , % til 100 mg til 200 mg 0 20 40 60 80 100 resurface 1 pga p at ie nt s , % pasi 75 pasi 90 pasi 100 0 20 40 60 80 100 resurface 1 til 200 mg p at ie nt s , % pasi 75 pasi 90 pasi 100 0 20 40 60 80 100 resurface 1 til 100 mg p at ie nt s , % pasi 75 pasi 90 pasi 100 0 20 40 60 80 100 resurface 2 til 100 mg p at ie nt s , % pasi 75 pasi 90 pasi 100 0 20 40 60 80 100 resurface 2 til 200 mg p at ie nt s , % til 100 mg til 200 mg 0 20 40 60 80 100 resurface 2 pga p at ie nt s , % til 100 mg til 200 mg 0 20 40 60 80 100 resurface 1 pga p at ie nt s , % pasi 75 pasi 90 pasi 100 0 20 40 60 80 100 resurface 1 til 200 mg p at ie nt s , % pasi 75 pasi 90 pasi 100 0 20 40 60 80 100 resurface 1 til 100 mg p at ie nt s , % pasi 75 pasi 90 pasi 100 0 20 40 60 80 100 resurface 2 til 100 mg p at ie nt s , % pasi 75 pasi 90 pasi 100 0 20 40 60 80 100 resurface 2 til 200 mg p at ie nt s , % til 100 mg til 200 mg 0 20 40 60 80 100 resurface 2 pga p at ie nt s , % til 100 mg til 200 mg 0 20 40 60 80 100 resurface 1 pga p at ie nt s , % pasi 75 pasi 90 pasi 100 0 20 40 60 80 100 resurface 1 til 200 mg p at ie nt s , % pasi 75 pasi 90 pasi 100 0 20 40 60 80 100 resurface 1 til 100 mg p at ie nt s , % 0 20 40 60 80 100 resurface 1 extension week p at ie nt s, % 0 12 24 36 48 60 72 84 120 14496 0 20 40 60 80 100 resurface 2 week p at ie nt s, % 52 60 64 76 88 100 112 124 136 148 172 196 pasi 75 (til 100 mg) pasi 90 (til 100 mg) pasi 100 (til 100 mg) pasi 75 (til 200 mg) pasi 90 (til 200 mg) pasi 100 (til 200 mg) til 100 mg n = 233 229 228 221 217 211 205 205 200 187 178 til 200 mg n = 264 263 262 250 256 253 252 248 241 235 226 til 100 mg n = 376 379 373 372 365 356 350 344 332 322 126 21 til 200 mg n = 344 348 345 340 338 333 324 313 307 298 136 19 a) b) 0 20 40 60 80 100 resurface 1 extension week p at ie nt s, % 0 12 24 36 48 60 72 84 120 14496 0 20 40 60 80 100 resurface 2 week p at ie nt s, % 52 60 64 76 88 100 112 124 136 148 172 196 pasi 75 (til 100 mg) pasi 90 (til 100 mg) pasi 100 (til 100 mg) pasi 75 (til 200 mg) pasi 90 (til 200 mg) pasi 100 (til 200 mg) til 100 mg n = 233 229 228 221 217 211 205 205 200 187 178 til 200 mg n = 264 263 262 250 256 253 252 248 241 235 226 til 100 mg n = 376 379 373 372 365 356 350 344 332 322 126 21 til 200 mg n = 344 348 345 340 338 333 324 313 307 298 136 19 a) b) 0 20 40 60 80 100 resurface 1 extension week p at ie nt s, % 0 12 24 36 48 60 72 84 120 14496 0 20 40 60 80 100 resurface 2 week p at ie nt s, % 52 60 64 76 88 100 112 124 136 148 172 196 pasi 75 (til 100 mg) pasi 90 (til 100 mg) pasi 100 (til 100 mg) pasi 75 (til 200 mg) pasi 90 (til 200 mg) pasi 100 (til 200 mg) til 100 mg n = 233 229 228 221 217 211 205 205 200 187 178 til 200 mg n = 264 263 262 250 256 253 252 248 241 235 226 til 100 mg n = 376 379 373 372 365 356 350 344 332 322 126 21 til 200 mg n = 344 348 345 340 338 333 324 313 307 298 136 19 a) b) 0 20 40 60 80 100 resurface 1 extension week p at ie nt s, % 0 12 24 36 48 60 72 84 120 14496 0 20 40 60 80 100 resurface 2 week p at ie nt s, % 52 60 64 76 88 100 112 124 136 148 172 196 pasi 75 (til 100 mg) pasi 90 (til 100 mg) pasi 100 (til 100 mg) pasi 75 (til 200 mg) pasi 90 (til 200 mg) pasi 100 (til 200 mg) til 100 mg n = 233 229 228 221 217 211 205 205 200 187 178 til 200 mg n = 264 263 262 250 256 253 252 248 241 235 226 til 100 mg n = 376 379 373 372 365 356 350 344 332 322 126 21 til 200 mg n = 344 348 345 340 338 333 324 313 307 298 136 19 a) b) 0 20 40 60 80 100 resurface 1 extension week p at ie nt s, % 0 12 24 36 48 60 72 84 120 14496 0 20 40 60 80 100 resurface 2 week p at ie nt s, % 52 60 64 76 88 100 112 124 136 148 172 196 pasi 75 (til 100 mg) pasi 90 (til 100 mg) pasi 100 (til 100 mg) pasi 75 (til 200 mg) pasi 90 (til 200 mg) pasi 100 (til 200 mg) til 100 mg n = 233 229 228 221 217 211 205 205 200 187 178 til 200 mg n = 264 263 262 250 256 253 252 248 241 235 226 til 100 mg n = 376 379 373 372 365 356 350 344 332 322 126 21 til 200 mg n = 344 348 345 340 338 333 324 313 307 298 136 19 a) b) 0 20 40 60 80 100 resurface 1 extension week p at ie nt s, % 0 12 24 36 48 60 72 84 120 14496 0 20 40 60 80 100 resurface 2 week p at ie nt s, % 52 60 64 76 88 100 112 124 136 148 172 196 pasi 75 (til 100 mg) pasi 90 (til 100 mg) pasi 100 (til 100 mg) pasi 75 (til 200 mg) pasi 90 (til 200 mg) pasi 100 (til 200 mg) til 100 mg n = 233 229 228 221 217 211 205 205 200 187 178 til 200 mg n = 264 263 262 250 256 253 252 248 241 235 226 til 100 mg n = 376 379 373 372 365 356 350 344 332 322 126 21 til 200 mg n = 344 348 345 340 338 333 324 313 307 298 136 19 a) b) 0 20 40 60 80 100 resurface 1 extension week p at ie nt s, % 0 12 24 36 48 60 72 84 120 14496 0 20 40 60 80 100 resurface 2 week p at ie nt s, % 52 60 64 76 88 100 112 124 136 148 172 196 pasi 75 (til 100 mg) pasi 90 (til 100 mg) pasi 100 (til 100 mg) pasi 75 (til 200 mg) pasi 90 (til 200 mg) pasi 100 (til 200 mg) til 100 mg n = 233 229 228 221 217 211 205 205 200 187 178 til 200 mg n = 264 263 262 250 256 253 252 248 241 235 226 til 100 mg n = 376 379 373 372 365 356 350 344 332 322 126 21 til 200 mg n = 344 348 345 340 338 333 324 313 307 298 136 19 a) b) 0 20 40 60 80 100 resurface 1 extension week p at ie nt s, % til 100 mg til 200 mg 0 12 24 36 48 60 72 84 120 14496 0 20 40 60 80 100 resurface 2 week p at ie nt s, % til 100 mg til 200 mg 52 60 64 76 88 100 112 124 136 148 172 196 til 100 mg n = 232 227 225 221 217 211 205 205 200 187 178 til 200 mg n = 262 263 259 245 254 250 250 247 240 235 226 til 100 mg n = 375 375 371 370 363 352 347 342 330 321 125 21 til 200 mg n = 341 345 342 337 335 330 321 310 304 295 135 19 a) b) 0 20 40 60 80 100 resurface 1 extension week p at ie nt s, % til 100 mg til 200 mg 0 12 24 36 48 60 72 84 120 14496 0 20 40 60 80 100 resurface 2 week p at ie nt s, % til 100 mg til 200 mg 52 60 64 76 88 100 112 124 136 148 172 196 til 100 mg n = 232 227 225 221 217 211 205 205 200 187 178 til 200 mg n = 262 263 259 245 254 250 250 247 240 235 226 til 100 mg n = 375 375 371 370 363 352 347 342 330 321 125 21 til 200 mg n = 341 345 342 337 335 330 321 310 304 295 135 19 a) b) 0 20 40 60 80 100 resurface 1 extension week p at ie nt s, % 0 12 24 36 48 60 72 84 120 14496 0 20 40 60 80 100 resurface 2 week p at ie nt s, % 52 60 64 76 88 100 112 124 136 148 172 196 pasi 75 (til 100 mg) pasi 90 (til 100 mg) pasi 100 (til 100 mg) pasi 75 (til 200 mg) pasi 90 (til 200 mg) pasi 100 (til 200 mg) til 100 mg n = 233 229 228 221 217 211 205 205 200 187 178 til 200 mg n = 264 263 262 250 256 253 252 248 241 235 226 til 100 mg n = 376 379 373 372 365 356 350 344 332 322 126 21 til 200 mg n = 344 348 345 340 338 333 324 313 307 298 136 19 a) b) 0 20 40 60 80 100 resurface 1 extension week p at ie nt s, % 0 12 24 36 48 60 72 84 120 14496 0 20 40 60 80 100 resurface 2 week p at ie nt s, % 52 60 64 76 88 100 112 124 136 148 172 196 pasi 75 (til 100 mg) pasi 90 (til 100 mg) pasi 100 (til 100 mg) pasi 75 (til 200 mg) pasi 90 (til 200 mg) pasi 100 (til 200 mg) til 100 mg n = 233 229 228 221 217 211 205 205 200 187 178 til 200 mg n = 264 263 262 250 256 253 252 248 241 235 226 til 100 mg n = 376 379 373 372 365 356 350 344 332 322 126 21 til 200 mg n = 344 348 345 340 338 333 324 313 307 298 136 19 a) b) conclusions • currently, there is no standardized approach for the diagnosis and management of advanced cscc • immunotherapy should be considered first-line systemic therapy, following its recent introduction into the treatment paradigm additional studies are needed on immunotherapy in immunosuppressed patients, and in combination with other treatment modalities • mdt discussion may be useful at key decision points or where additional specialist input is needed. mdt recommendations should be discussed with the patient • further research is needed in several areas (e.g. the role of curative radiation therapy, combination therapies, and the validation of biomarkers) • the excel consensus program outputs may provide physicians with practical recommendations to optimize outcomes for patients with advanced cscc author disclosure g rabinowits: reports consulting/advisory relationship and scientific advisory boards with castle biosciences, emd serono, merck, pfizer,regeneron pharmaceuticals, and sanofi genzyme. additionally, he holds regeneron pharmaceuticals and syros pharmaceuticals shares; mr migden: reports honoraria from eli lilly, novartis, regeneron pharmaceuticals, institutional research funding from genentech, sun pharmaceutical industries limited, and sanofi genzyme; te schlesinger: reports research funding from abbvie, aclaris, allergan, bmi, biofrontera, bristol-myers squibb, celgene, dermavant, dermira, eli lilly, galderma, kiniksa, merz, novartis, pfizer, and sisaf; honoraria and consulting/advisory relationship from/with aclaris, allergan, almirall, dermira, ortho, regeneron pharmaceuticals, sanofi genzyme, and sun pharmaceutical industries limited; cd schmults: reports consultant fees and grant research funding from castle biosciences and regeneron pharmaceuticals; research funding from novartis; rl ferris: reports honoraria from amgen, bain capital life sciences, emd serono, glaxosmithkline, iovance, biotherapeutics, eli lilly,numab therapeutics ag, oncorus, ono pharmaceutical, pfizer, ppd, regeneron pharmaceuticals, ttms, and venti rx pharmaceuticals; research funding and honoraria from astrazeneca/medimmune, bristol-myers squibb, merck, and tesaro; m freeman: reports scientific advisory board and consultant fees with/from regeneron pharmaceuticals and sanofi genzyme; speaker for regeneron pharmaceuticals; v guild: no disclosures; s koyfman: reports research funding from merck; ac pavlick: reports consulting/advisory relationship, scientific advisory boards, and research funding with/from regeneron pharmaceuticals and sanofi genzyme; n swanson: reports consulting/advisory relationship with genentech, regeneron pharmaceuticals, and sanofi genzyme; gt wolf: reports honoraria from merck and regeneron pharmaceuticals; research funding from brooklyn immunotherapeutics; sm dinehart: reports consulting/advisory relationship and scientific advisory boards with regeneron pharmaceuticals and sanofi genzyme; consulting/ advisory relationship with genentech; scientific advisory boards with verrica pharmaceuticals. references 1. karia ps, et al. j am acad dermatol 2013;68:957-966. 2. rogers hw, et al. jama dermatol 2015;151:10811086. 3. national comprehensive cancer network. squamous cell skin cancer (version 2.2019). accessed july 30, 2019. 4. work g, et al. j am acad dermatol 2018;78:560-578. 5. arunachalam d, et al. indian j palliat care 2011;17:184-190. 6. berens am, et al. curr opin otolaryngol head neck surg 2017;25:258-264. 7. amin mb, et al. ca cancer j clin 2017;67:93-99. 8. karia ps, et al. j clin oncol 2014;32:327-334. acknowledgement the excel program is funded by the sanofi genzyme and regeneron alliance. the excel committee (composed of all listed authors) is solely responsible for all aspects of developing the consensus statements and the funding source had no role in drafting or voting on the statements. editorial and organizational supports were provided by lighthouse (a lucid group company). the authors maintained complete control over the direction and content of the consensus statements. no payments were made to the authors for the writing of this poster and authors approved the final contents. *consensus was achieved if ≥75% of participants scored the recommendation within the 7–9 range and ≤25% scored it within the 1–3 range period figure 1. modified delphi process for the consensus process question development steering committee statements development voting draft questions refine, rank and finalize questions support literature research, review, and summary bibliographic fellows literature research, summary report, and draft statements consensus recommendations* figure 2. literature research and review process • databases included pubmed and google scholar • key abstracts from congresses were also included (e.g. from american society of clinical oncology, the european academy of dermatology and venereology, the american academy of dermatology, and the society for investigative dermatology) 5471 references were identified and screened 161 references were used to develop final recommendations considerations for the management of advanced cscc select consensus statements and key recommendations radiation therapy for advanced cscc may be considered in the following settings consensus • adjuvant radiation therapy may be considered in patients with uncertain surgical margins (e.g. multifocal or large caliber nerve invasion, or lymphovascular invasion) or with a recurrent tumor. adjuvant radiation was associated with a lower risk of local recurrence in primary tumors with large caliber (>0.1 mm) nerve invasion in a single study 75% • definitive radiation therapy versus systemic therapy may be considered when gross disease is present and is not amenable to surgical resection. however, efficacy of radiation has not been investigated in grossly unresectable cscc imaging is strongly suggested when clinical evaluation for assessment of response is insufficient following definitive radiation therapy. imaging modalities may include ct, pet, pet/ct, mri, and ultrasound and should be selected based on clinical information and available evidence • adjuvant radiation may be considered for local control of microscopic residual disease that cannot be surgically resected note: given the approval of cemiplimab, the curative confidence and morbidity of definitive, single modality radiation therapy should be considered, discussed with the patient, and weighed against systemic options such as immunotherapy immunotherapy in the management of advanced cscc consensus • cemiplimab is the only fda approved therapy for use in patients with la or metastatic cscc who are not candidates for curative surgery or curative radiation. the approval was based on phase i/ii data. cemiplimab should be used as first line therapy in patients requiring systemic treatment 87.5% • appropriate use of cemiplimab in immunosuppressed patients has not been established as they have been excluded from trials published so far. however, cemiplimab treatment is not necessarily precluded in these patients 87.5% • treatment decisions should weigh the risk of death and disability from the tumor versus the risk of immunotherapy, which can provoke exacerbations of autoimmune conditions (e.g. lupus, colitis) and organ rejection in organ transplant recipients, which can lead to rapid death in patients with lung, heart, and liver transplant 87.5% • in the neoadjuvant and adjuvant settings, treatment of cscc with immunotherapy is under investigation via clinical trials. enrollment of eligible patients in these trials is strongly encouraged 100% chemotherapy or targeted therapy for the management of advanced cscc consensus • chemotherapy or targeted therapy can be considered in patients who are not candidates for immunotherapy, who have progressed on immunotherapy, or who cannot tolerate immunotherapy related adverse events. however, response rates are low and generally of short duration. the adverse event profile may be more serious, depending on the choice of therapy 87.5% • currently, there is no standard of care for neoadjuvant or adjuvant systemic therapy in advanced cscc. in patients with la and metastatic cscc, immunotherapy should be considered first line, followed by targeted therapy and/or chemotherapy 75% synoptic pathology for cscc should include the following minimum key requirements consensus • clinical preoperative tumor diameter (provided to the pathologist by the surgeon) 89% • millimeter thickness or tissue level of invasion • millimeter depth measured from the granular layer of adjacent normal epidermis to base of tumor (breslow thickness) • tissue level depth of tumor invasion (e.g. dermis, fat, fascia) • tumor differentiation (well, moderate, poor, undifferentiated) • desmoplasia • perineural invasion (pni) nerve caliber ≥0.1 mm or invasion of a nerve lying deep to dermis • extent of lymphocyte infiltration (immunoscore) • lymphovascular invasion • specify if the tumor may represent a metastasis criteria for la cscc and metastatic cscc consensus • la cscc is a local tumor where surgery or radiation is unlikely to obtain clearance of the tumor, or where the patient is not a candidate for surgery or radiation due to an inability to safely reconstruct the wound, or due to high morbidity unacceptable to the patient 82% • metastatic cscc can be defined as disease that has spread from the original site to a distant organ or in subcutaneous tissues beyond the draining lymph nodes of the primary cscc location note: in transit metastasis (biopsy proven cscc in dermal and subcutaneous tissue in the area between the primary cscc and its draining lymph nodes) is classified as la disease 87.5% criteria for ‘non candidacy for surgery’ for patients with advanced disease consensus • appropriateness for surgery can be best assessed by a surgeon including but not limited to mohs surgeons, head and neck surgeons, and oncologic surgeons with experience treating patients with advanced cscc. a multidisciplinary discussion of therapeutic options with oncologists, radiation oncologists, and patients’ primary physicians can be helpful in weighing risks and benefits of various treatment approaches, also considering patient comorbidities. for complex cases second opinions are encouraged 89% • the appropriateness of resection should be discussed with the patient. this discussion should include the likelihood of tumor clearance with surgery and any significant risk of morbidity to determine whether the morbidity is acceptable to the patient 89% the use of different staging systems for the management of advanced cscc7,8 consensus • the bwh t staging system may be used to estimate risk of recurrence and metastasis and identify patients who may benefit from radiologic nodal staging or increased surveillance for recurrence • ajcc8 n2 identifies patients at increased risk of regional treatment failure after surgery +/ radiation. these patients may benefit from consideration of systemic therapy if such failure occurs or the nodal disease is inoperable • metastases to distant organs identifies patients in need of systemic therapy 78% • based on the current evidence, tumor (t) staging does not have a prominent role in determining appropriateness for systemic therapy including immunotherapy in patients with advanced cscc. however, nodal (n) and metastasis (m) staging systems do play a role 78% patient/tumor characteristics suggesting increased risk for recurrence and/or metastatic disease consensus • tumor diameter ≥2 cm, presence of desmoplasia, tumor thickness (breslow thickness), tissue level of invasion, caliber of perineural invasion, bone erosion and poor differentiation are independent risk factors for local recurrence, metastasis, and/or death from disease in patients with cscc 89% supplemental tests to identify tumor characteristics suggestive of increased risk for recurrence and/or metastatic disease consensus • molecular tests are being investigated and should not be used to make treatment decisions. future development of molecular staging tests may provide better risk stratification. however, until more conclusive evidence is available, molecular tests should not be used to guide treatment or referral decisions 100% identification, staging, and risk stratification of advanced cscc a multidisciplinary expert-driven consensus on the evolving treatment of patients with advanced cutaneous squamous cell carcinoma background • cutaneous squamous cell carcinoma (cscc) is the second most common skin cancer, with an estimated annual incidence of ~700,000 in the us resulting in over 8000 deaths/year1,2 • radiotherapy, chemotherapy, and targeted therapy are available for the management of advanced cscc, defined as metastatic or locally advanced disease not amenable to surgery or radiation; however, there is a lack of randomized clinical trial data for these options and no standardized management approach3,4 • in addition to the medical burden of cscc, patients suffer poor quality of life from functional loss, impairing surgeries, and the psychosocial impact of the disease5,6 objective • the aim of the excel program was to help standardize patient characterization and develop evidence-based consensus statements for advanced cscc with respect to tumor staging, work up, treatment and surveillance with the aim of providing up-to-date practical recommendations for physicians methods • in october 2018, a multidisciplinary steering committee (sc) of experts in the field of advanced cscc was convened (five dermatologists [including four mohs surgeons], three medical oncologists, two head and neck surgeons, two radiation oncologists, and a patient) • a modified delphi process was used to develop consensus recommendations (figure 1): 1. five key areas of focus were identified (diagnosis, staging systems and risk stratification, treatment modalities in advanced cscc, referral patterns, and patient perspective) 2. fourteen key questions were developed, ranked and refined to identify clinical gaps. a final list of 12 questions were selected to develop consensus statements 3. ten bibliographic fellows performed a robust literature review to gather evidence and draft statements for each question (figure 2). statements were refined by the sc for consensus voting 4. the sc refined and finalized recommendations during three online voting sessions michael r. migden,1 todd e. schlesinger,2 chrysalyne d. schmults,3 scott m.dinehart,4 robert l. ferris,5 morganna freeman,6 valerie guild,7 shlomo koyfman,8 anna c. pavlick,9 gregory t. wolf,10 guilherme rabinowits,11 neil swanson.12 1. md anderson cancer center, houston, tx; 2. dermatology & laser center of charleston, charleston, sc; 3. brigham and women’s hospital, harvard medical school, boston,ma; 4. arkansas skin cancer center, little rock, ar; 5.upmc hillman cancer center, pittsburgh,pa; 6.city of hope, duarte, ca; 7. aim at melanoma foundation, plano, tx; 8. cleveland clinic, cleveland, oh; 9.nyu langone health, new york city, ny; 10. university of michigan, ann arbor, mi; 11. miami cancer institute, fl; 12. oregon health & science university, portland, or. involving multidisciplinary team in patient care consensus • patients with la or metastatic cscc may benefit from an mdt discussion including experts in cscc from the areas of surgery, medicine, and radiation. such experts include (but are not limited to) medical oncologists, dermatologists/dermato oncologists, surgical oncologists (including head and neck and mohs surgeons), and radiation oncologists 100% an oral, selective tyrosine kinase 2 inhibitor, bms-986165, reduced absolute psoriasis area and severity index in a phase 2 trial in psoriasis bruce strober,1 alice b. gottlieb,2 diamant thaçi,3 luis puig,4 matthew j. colombo,5 sudeep kundu,5 renata kisa,5 subhashis banerjee5 1yale university, new haven, ct, and central connecticut dermatology research, cromwell, ct, usa; 2icahn school of medicine at mount sinai, new york, ny, usa; 3research institute and comprehensive center for inflammation medicine, university of lübeck, lübeck, germany; 4hospital de la santa creu i sant pau, universitat autònoma de barcelona, barcelona, spain; 5bristol-myers squibb company, princeton, nj, usa conclusions • this analysis suggests that bms-986165 elicits a rapid response and is efficacious in achieving an absolute pasi of ≤2 in approximately 50% of patients and an absolute pasi ≤1 in approximately 30% of patients with moderate to severe plaque psoriasis — as mentioned earlier, an absolute pasi of ≤2 has been shown to be clinically meaningful for clinical and hrqol outcomes2 — mean percentage change from baseline in absolute pasi at week 12 was approximately 80% in bms-986165–treated patients • five ongoing phase 3 trials in plaque psoriasis (nct03624127, nct03611751, nct04167462, nct03924427, and nct04036435) involving bms-986165 treatment will evaluate this further over a longer duration and in larger patient cohorts • pasi ≤2 has the potential to be an alternative therapeutic goal to percent pasi improvements and spga scores for patients with moderate to severe plaque psoriasis introduction • plaque psoriasis is a debilitating, chronic, immune-mediated skin disorder that impairs patients’ healthrelated quality of life (hrqol) and productivity1 • treatment outcomes for plaque psoriasis based on the absolute psoriasis area and severity index (pasi) are indicative of an individual patient’s disease severity at the time of analysis2 — absolute pasi may be more clinically meaningful than percentage change in pasi from baseline captured by scores such as pasi 75 (≥75% reduction from baseline pasi)2 — although a consensus therapeutic target has yet to be defined, a recent analysis reported that attainment of an absolute pasi of ≤2 translates to meaningful improvements in clinical and hrqol outcomes2 • previous studies have demonstrated that an absolute pasi ≤2 correlates with pasi 90 (≥90% improvement from baseline pasi), static physician’s global assessment (spga) score of 0/1 (range, 0–5; higher scores indicate greater disease severity), and dermatology life quality index (dlqi) of 0/1 (range, 0–30; higher scores indicate worse hrqol)2 • bms-986165 is an oral, selective, allosteric inhibitor of tyrosine kinase 2 (tyk2), an intracellular enzyme involved in key cytokine signaling pathways in plaque psoriasis pathogenesis3 — in a phase 2, double-blind, randomized trial in patients with moderate to severe plaque psoriasis (nct02931838), 67%–75% of patients treated with bms-986165 at doses of 3 or 6 mg twice daily (bid) or 12 mg once daily (qd) achieved pasi 75 at week 12 (primary endpoint) vs 7% with placebo (p<0.001)3 — bms-986165 had a favorable safety and tolerability profile, and was associated with low rates of treatment discontinuation3 objective • this post hoc analysis of the phase 2 trial compared the efficacy of bms-986165 vs placebo based on absolute pasi over time up to week 12 methods inclusion criteria • adults with body mass index of 18–40 kg/m2 • moderate to severe plaque psoriasis for ≥6 months affecting ≥10% of body surface area — pasi ≥12 (range, 0–72; higher scores indicate greater disease severity) — spga ≥3 • eligible for phototherapy or systemic therapy exclusion criteria • diagnosis of nonplaque psoriasis or other immune-mediated condition requiring concomitant systemic immunosuppressant therapy • history or evidence of specific infections (eg, hiv or hepatitis b or c infection) or risk of tuberculosis • previous lack of response to any therapeutic agent targeting the tyk2 pathway (eg, interleukin-12/-23 pathways) treatment • patients were randomized equally to 1 of 5 oral doses of bms-986165 (3 mg every other day, 3 mg qd, 3 mg bid, 6 mg bid, or 12 mg qd) or matching oral placebo for 12 weeks study endpoints • this post hoc analysis assessed the following efficacy endpoints in the 3 most effective bms-986165 dose groups (3 mg bid, 6 mg bid, 12 mg qd) vs placebo — mean absolute pasi over time — mean percentage change from baseline in absolute pasi over time — percentage of patients at week 12 who achieved an absolute pasi of ≤1, ≤2, ≤3, and ≤5 statistical analysis • this post hoc efficacy analysis was performed in the efficacy analysis population • absolute pasi over time and within predefined categories are expressed as patient numbers and percentages • patients who discontinued the treatment regimen early or who had a missing value at any time point had outcomes imputed as a nonresponse at that time point, regardless of response status at time of discontinuation results baseline demographics and disease characteristics • 179 patients were included in this post hoc analysis (bms-986165 groups, n=134; placebo, n=45) • baseline demographics and disease characteristics of patients in each dose group are presented in table 1 — most patients were male (58%–82% across treatment groups), mean patient age was 43–47 years, and mean body mass index was 27–30 kg/m2 — baseline mean pasi was similar across treatment groups (18–19) • median disease duration was 13–20 years and 41%–44% of patients had received prior biologic therapy table 1. baseline demographics and disease characteristics3 bms-986165 characteristica placebo (n=45) 3 mg bid (n=45) 6 mg bid (n=45) 12 mg qd (n=44) demographic characteristics mean age, y 46 ± 12 46 ± 15 43 ± 13 47 ± 12 male sex, n (%) 37 (82) 26 (58) 35 (78) 30 (68) race, n (%) white 40 (89) 39 (87) 35 (78) 37 (84) asian 5 (11) 5 (11) 9 (20) 6 (14) other 0 1 (2) 1 (2) 1 (2) body weight, kg 96 ± 21 84 ± 18 84 ± 19 88 ± 24 body mass index, kg/m2 30 ± 6 28 ± 5 27 ± 5 29 ± 5 clinical characteristics median (range) disease duration, y 18 (2–48) 13 (1–61) 15 (1–55) 20 (1–47) prior use of biologic therapy, n (%) 20 (44) 19 (42) 20 (44) 18 (41) pasib 19 ± 6 19 ± 8 18 ± 6 18 ± 5 dlqic 13 ± 7 13 ± 5 11 ± 6 13 ± 7 body surface area, % 24 ± 13 24 ± 15 25 ± 13 21 ± 12 from n engl j med, papp k, gordon k, thaçi d, et al, phase 2 trial of selective tyrosine kinase 2 inhibition in psoriasis, 379(14):1313-1321. copyright © 2018 massachusetts medical society. reprinted with permission. bid, twice daily; dlqi, dermatology life quality index; pasi, psoriasis area and severity index; qd, once daily. avalues are means ± sd unless otherwise noted. data have been rounded to the nearest integer. percentages may not total 100 because of rounding. bpasi ranges from 0–72, with higher scores indicating greater severity of psoriasis. cdlqi scores range from 0–30, with higher scores indicating worse quality of life. absolute pasi • bms-986165 was associated with lower absolute pasi compared with placebo up to week 12 (figure 1) — each of the 3 bms-986165 doses evaluated resulted in similar levels of improvement in median absolute pasi over time 2020 pa & np fall clinical dermatology conference, november 13–15, 2020, orlando, florida copies of this poster obtained through quick response (qr) code are for personal use only and may not be reproduced without written permission from the authors of this poster. references 1. weigle n, mcbane s. am fam physician. 2013;87(9):626-633. 2. puig l et al. acta derm venereol. 2019;99(11):971-977. 3. papp k et al. n engl j med. 2018;379(14):1313-1321. acknowledgments • this work was sponsored by bristol-myers squibb company. professional medical writing from ann marie fitzmaurice, phd and editorial assistance were provided by peloton advantage, llc, an open health company, parsippany, nj, and were funded by bristol-myers squibb company. relationships and activities • bs: honoraria or consultation fees: abbvie, almirall, amgen, arena, boehringer ingelheim, bristol-myers squibb, celgene, dermavant, dermira, eli lilly, gsk, janssen, kyowa hakko kirin, leo pharma, medac, meiji seika pharma, novartis, ortho dermatologics, pfizer, regeneron, sanofi-genzyme, sun pharma, ucb; speaker: abbvie, eli lilly, janssen, ortho dermatologics; scientific director (consulting fee): corrona psoriasis registry; investigator: abbvie, corrona psoriasis registry, dermavant, dermira. • abg: grant/research funding (paid to institution): boehringer ingelheim, incyte, janssen-ortho, novartis, ucb, xbiotech; honoraria or consultation fees (paid to abg): abbott (abbvie), amgen, bristol-myers squibb, celgene, eli lilly, incyte, janssen biotech, janssen-ortho, leo pharma, lilly icos, novartis, sun pharma, ucb, xbiotech, avotres (no direct compensation received from avotres); stock options: xbiotech. • dt: research support/principal investigator (clinical trials): abbvie, almirall, amgen, biogen idec, boehringer ingelheim, celgene, chugai, dermira, ds-pharma, eli lilly, galderma, gsk, janssen-cilag, leo pharma, msd, novartis, pfizer, regeneron, roche, sandoz-hexal, sanofi, ucb; consultant: abbvie, almirall, celgene, dignity, galapagos, leo pharma, maruho, mitsubishi, novartis, pfizer, xenoport; lectures: abbvie, almirall, amgen, ds-pharma, janssen, leo pharma, msd, novartis, pfizer, la roche-posay, sandoz-hexal, sanofi, target-solution, ucb; scientific advisory board: abbvie, amgen, celgene, ds-pharma, eli lilly, galapagos, janssen-cilag, leo pharma, morphosis, msd, novartis, pfizer, sandoz, sanofi, ucb. • lp: grant/research support or participation in clinical trials (paid to institution): abbvie, almirall, amgen, boehringer ingelheim, celgene, eli lilly, janssen, leo pharma, novartis, pfizer, regeneron, roche, sanofi, ucb; honoraria or consultation fees (paid to lp): abbvie, almirall, amgen, baxalta, biogen, boehringer ingelheim, celgene, eli lilly, fresenius kabi, gebro, janssen, leo pharma, merck-serono, msd, mylan, novartis, pfizer, regeneron, roche, samsung bioepis, sandoz, sanofi, ucb; speakers bureau: celgene, eli lilly, janssen, msd, novartis, pfizer. • mjc, sk, rk, and sb: employees and shareholders of bristol-myers squibb company. to request a copy of this poster: scan qr code via a barcode reader application scientific content on demand qr codes are valid for 30 days after the congress date. figure 1. median absolute pasi through week 12 0 5 10 15 20 25 35 30 40 45 a b so lu te p a si baseline week 4 week 8 week 12 3 mg bidplacebo 6 mg bid 12 mg qd bms-986165 bid, twice daily; pasi, psoriasis area and severity index; qd, once daily. • bms-986165 was also associated with greater reductions in mean percentage change from baseline in absolute pasi than placebo from week 1 to week 12 (figure 2) figure 2. mean percentage change from baseline in absolute pasi through week 12 3 mg bidplacebo 6 mg bid 12 mg qd bms-986165 0 2 6 104 8 12 time (weeks) -90 -80 -70 -60 -50 -40 -30 -20 -10 0 m e an ± s e p e rc e n ta ge c h an ge f ro m b as e li n e i n a b so lu te p a si bid, twice daily; pasi, psoriasis area and severity index; qd, once daily. • the percentages of patients achieving absolute pasi values of ≤1, ≤2, ≤3, and ≤5 at week 12 were higher in the bms-986165 groups than in the placebo group (table 2) table 2. absolute pasi at week 12 patients achieving pasi threshold, % (intent-to-treat population) absolute pasi placebo (n=45) bms-986165 3 mg bid (n=45) bms-986165 6 mg bid (n=45) bms-986165 12 mg qd (n=44) bms-986165 combined (n=134) ≤1 0 24.4 33.3 34.1 30.6 ≤2 0 46.7 44.4 50.0 47.0 ≤3 2.2 57.8 53.3 63.6 58.2 ≤5 8.9 73.3 64.4 77.3 71.6 bid, twice daily; pasi, psoriasis area and severity index; qd, once daily. patients who discontinued the treatment regimen early or who had a missing value at any time point had outcomes imputed as a nonresponse at that time point, regardless of response status at time of discontinuation. http://www.globalbmsmedinfo.com deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, in moderate to severe plaque psoriasis: 52-week efficacy by prior treatment in the phase 3 poetyk pso-1 trial jerry bagel,1 april w armstrong,2 richard b warren,3 kim a papp,4 diamant thaçi,5 alan menter,6 jennifer cather,7 matthias augustin,8 lauren hippeli,9 carolin daamen,9 christopher e m griffiths3 1psoriasis treatment center of new jersey, east windsor, nj, usa; 2university of southern california, los angeles, ca, usa; 3dermatology centre, salford royal nhs foundation trust, nihr manchester biomedical research centre, the university of manchester, manchester, uk; 4k papp clinical research and probity medical research, waterloo, on, canada; 5institute and comprehensive center for inflammation medicine, university of lübeck, lübeck, germany; 6baylor university medical center, dallas, tx, usa; 7mindful dermatology and modern research associates, dallas, tx, usa; 8institute for health services research in dermatology and nursing, university medical center hamburg-eppendorf, hamburg, germany; 9bristol myers squibb, princeton, nj, usa presented at the winter clinical dermatology conference hawaii®, january 13-18, 2023, kohala coast, hi, and winter clinical miamitm, february 17-20, 2023, miami, fl this is an encore of the 2022 31st eadv congress presentation email: dreamacres1@icloud.com copies of this poster are for personal use only and may not be reproduced without written permission from the authors. synopsis • deucravacitinib an oral, selective, allosteric tyrosine kinase 2 (tyk2) inhibitor, is approved by the us food and drug administration for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy1 — uniquely binds to the regulatory domain rather than to the catalytic domain where janus kinase (jak) 1/2/3 inhibitors bind2,3 (figure 1) • in the global, 52-week, phase 3 poetyk pso-1 trial (nct03624127), deucravacitinib was significantly more effective than placebo or apremilast in the treatment of moderate to severe plaque psoriasis4 — clinical responses were maintained through 52 weeks5 • response rates for the coprimary endpoints, ≥75% reduction from baseline in psoriasis area and severity index (pasi 75) and static physician’s global assessment score of 0 (clear) or 1 (almost clear) with a ≥2-point improvement from baseline (spga 0/1) at week 16, were superior with deucravacitinib regardless of prior exposure to biologics, systemic nonbiologics, and/or phototherapy6 • the 2-year efficacy and safety of deucravacitinib in the poetyk long-term extension trial was consistent with weeks 0–52 of the poetyk pso-1 and pso-2 trials7 objective • the aim of the current analysis was to evaluate the impact of prior treatment on pasi 75 and spga 0/1 responses through week 52 in patients from poetyk pso-1 who were randomized to deucravacitinib and in those who crossed over from placebo to deucravacitinib at week 16 methods • the study design for poetyk pso-1 is illustrated in figure 2 • eligible patients were ≥18 years of age with moderate to severe plaque psoriasis (ie, pasi ≥12, spga ≥3, body surface area involvement ≥10% at baseline) • patients who previously received phototherapy, systemic treatment, and/or biologic treatment were required to complete washout periods ranging from 4 weeks to 6 months before study entry, depending on the treatment • the current analysis examined pasi 75 and spga 0/1 responses through 52 weeks in patients randomized to deucravacitinib and in those who crossed over from placebo to deucravacitinib at week 16 (placebo crossovers), by prior treatment subgroups: — systemic treatment naive (ie, neither biologic nor nonbiologic systemic treatment) — prior systemic treatment (biologic and/or nonbiologic) — prior oral systemic treatment (nonbiologic only) — biologic treatment naive — biologic treatment experienced • nonresponder imputation was used for all reported endpoints figure 2. poetyk pso-1 study design poetyk pso-1 (n = 666) deucravacitinib 6 mg qdplacebo (n = 166) deucravacitinib 6 mg qd apremilast 30 mg bid titrate* 1 :2 :1 r an d o m iz at io n weeks 16 24 520 deucravacitinib 6 mg qd (n = 332) primary endpoint apremilast 30 mg bida (n = 168) <pasi 50 ≥pasi 50 from armstrong aw, et al. deucravacitinib versus placebo and apremilast in moderate to severe plaque psoriasis: efficacy and safety results from the 52-week, randomized, double-blinded, placebo-controlled phase 3 poetyk pso-1 trial. j am acad dermatol. 2023;88:29-39. this work is licensed under a creative commons attribution license (cc by-nc-nd 4.0). https://creativecommons.org/licenses/by-nc-nd/4.0/. aapremilast was titrated from 10 mg qd to 30 mg bid over the first 5 days of dosing. bid, twice daily; pasi 50, ≥50% reduction from baseline in psoriasis area and severity index; qd, once daily. results • baseline demographics and disease characteristics for patients randomized to deucravacitinib (n = 332) and to placebo (n = 166) are shown in table 1 — prior use of systemic (biologic and nonbiologic), oral systemic, and biologic treatments was generally similar between the groups (table 1) • at week 52, pasi 75 response rates were similar in patients randomized to deucravacitinib at baseline and in placebo crossovers (65.1% and 68.3%, respectively) (table 2; figure 3) • these findings were consistent across all patient subgroups (table 2), including: — systemic treatment-naive patients and those with prior systemic or oral systemic treatment (figure 4) — patients with and without prior biologic treatment (figure 5) • at week 52, spga 0/1 response rates were similar in patients randomized to deucravacitinib at baseline and in placebo crossovers (53.8% and 52.7%, respectively) (figure 6) • these findings were consistent across all patient subgroups (table 2), including: — systemic treatment-naive patients and those with prior systemic or oral systemic treatment (figure 7) — patients with and without prior biologic treatment (figure 8) table 1. baseline patient demographics and disease characteristics parameter poetyk pso-1 placebo (n = 166) deucravacitinib (n = 332) age, mean (min, max), y 47.9 (19, 81) 45.9 (18, 80) weight, mean (min, max), kg 89.1 (46.3, 181.6) 87.9 (36.0, 173.0) female, n (%) 53 (31.9) 102 (30.7) race, n (%) white 128 (77.1) 267 (80.4) asian 34 (20.5) 59 (17.8) other 4 (2.4) 6 (1.8) disease duration, mean (min, max), y 17.3 (0.9, 62.3) 17.1 (0.7, 57.8) spga, n (%) 3 (moderate) 128 (77.1) 257 (77.4) 4 (severe) 37 (22.3) 75 (22.6) pasi, mean (min, max) 20.7 (10.3, 47.7) 21.8 (12.0, 58.8) pssd symptom score, mean (min, max) 51.4 (0.3, 100.0) 51.7 (0.0, 100.0) dlqi, mean (min, max) 11.4 (1.0, 30.0) 12.0 (0.0, 30.0) prior treatment use, n (%) systemic treatment naive 57 (34.3) 132 (39.8) prior systemic treatment 109 (65.7) 200 (60.2) prior oral systemic treatment 73 (44.0) 114 (34.3) biologic treatment naive 103 (62.0) 202 (60.8) prior biologic treatment 63 (38.0) 130 (39.2) dlqi, dermatology life quality index; pasi, psoriasis area and severity index; pssd, psoriasis symptoms and signs diary; spga, static physician’s global assessment. table 2. summary of week 52 response rates (nri)a patients poetyk pso-1 pasi 75 week 52 response rate, n/n (%) spga 0/1 week 52 response rate, n/n (%) placebo – deucravacitinib deucravacitinib placebo – deucravacitinib deucravacitinib full analysis set 99/145 (68.3) 216/332 (65.1) 78/145 (53.8) 175/332 (52.7) systemic treatment naive 35/51 (68.6) 85/132 (64.4) 26/51 (51.0) 69/132 (52.3) prior systemic treatment 64/94 (68.1) 131/200 (65.5) 52/94 (55.3) 106/200 (53.0) prior oral systemic treatment 45/65 (69.2) 80/114 (70.2) 35/65 (53.8) 65/114 (57.0) biologic treatment naive 65/90 (72.2) 136/202 (67.3) 53/90 (58.9) 113/202 (55.9) prior biologic treatment 34/55 (61.8) 80/130 (61.5) 25/55 (45.5) 62/130 (47.7) apatients who missed efficacy assessments due to covid-19 were excluded from efficacy analyses at those time points. nri, nonresponder imputation; pasi 75, ≥75% reduction from baseline in psoriasis area and severity index; spga 0/1, static physician’s global assessment score of 0 (clear) or 1 (almost clear) with a ≥2-point improvement from baseline. figure 3. pasi 75 response rates through week 52, full analysis set (nri)a 58.4% 65.1% 12.7% 68.3% 0 10 20 30 40 50 60 p a si 7 5 re sp on se r at e, % o f pa ti en ts 70 80 90 100 0 1 2 4 8 12 16 primary endpoint 20 weeks 24 28 32 36 40 44 48 52 332 332 332 332 332 332 332 332 332 332 330 326 320 324 325 332 166 deucravacitinib patients, n placebo – deucravacitinib 166 166 166 166 166 166 145 145 144 144 145 142 144 145 145 deucravacitinib placebo → deucravacitinib apatients who missed efficacy assessments due to covid-19 were excluded from efficacy analyses at those time points. nri, nonresponder imputation, pasi 75, ≥75% reduction from baseline in psoriasis area and severity index. figure 4. pasi 75 response rates through week 52 in systemic treatment-naive, prior systemic treatment, and prior oral systemic treatment patients (nri)a 0 10 20 30 40 50 60 p a si 7 5 re sp on se r at e, % o f pa ti en ts 70 80 90 100 0 1 2 4 8 12 16 primary endpoint 20 weeks systemic treatment naive 24 28 32 36 40 44 48 52 132 132 132 132 132 132 132 132 132 132 132 127 122 127 129 132 57 57 57 57 57 57 57 51 51 51 51 51 50 51 51 51 56.8% 64.4% 21.1% 68.6% 0 10 20 30 40 50 60 p a si 7 5 re sp on se r at e, % o f pa ti en ts 70 80 90 100 0 1 2 4 8 12 16 primary endpoint 20 weeks prior systemic treatment 24 28 32 36 40 44 48 52 200 200 200 200 200 200 200 200 200 200 198 199 198 197 196 200 109 109 109 109 109 109 109 94 94 93 93 94 92 93 94 94 59.5% 65.5% 8.3% 68.1% 0 10 20 30 40 50 60 p a si 7 5 re sp on se r at e, % o f pa ti en ts 70 80 90 100 0 1 2 4 8 12 16 primary endpoint 20 weeks prior oral systemic treatment 24 28 32 36 40 44 48 52 114 114 114 114 114 114 114 114 114 114 113 113 113 112 111 114 73 73 73 73 73 73 73 65 65 65 65 65 65 65 65 65 58.8% 70.2% 9.6% 69.2% deucravacitinib placebo → deucravacitinib deucravacitinib patients, n placebo – deucravacitinib deucravacitinib patients, n placebo – deucravacitinib deucravacitinib patients, n placebo – deucravacitinib apatients who missed efficacy assessments due to covid-19 were excluded from efficacy analyses at those time points. nri, nonresponder imputation; pasi 75, ≥75% reduction from baseline in psoriasis area and severity index. figure 5. pasi 75 response rates through week 52 in biologic treatment-naive and prior biologic treatment patients (nri)a 0 10 20 30 40 50 60 p a si 7 5 re sp on se r at e, % o f pa ti en ts 70 80 90 100 0 1 2 4 8 12 16 primary endpoint 20 weeks biologic treatment naive 24 28 32 36 40 44 48 52 202 202 202 202 202 202 202 202 202 202 202 197 192 195 196 202 103 103 103 103 103 103 103 90 90 90 90 90 89 90 90 90 0 10 20 30 40 50 60 p a si 7 5 re sp on se r at e, % o f pa ti en ts 70 80 90 100 0 1 2 4 8 12 16 primary endpoint 20 weeks prior biologic treatment 24 28 32 36 40 44 48 52 130 130 130 130 130 130 130 130 130 130 128 129 128 129 129 130 63 63 63 63 63 63 63 55 55 54 54 55 53 54 55 55 59.9% 67.3% 15.5% 72.2% 56.2% 61.5% 7.9% 61.8% deucravacitinib placebo → deucravacitinib deucravacitinib patients, n placebo – deucravacitinib deucravacitinib patients, n placebo – deucravacitinib apatients who missed efficacy assessments due to covid-19 were excluded from efficacy analyses at those time points. nri, nonresponder imputation; pasi 75, ≥75% reduction from baseline in psoriasis area and severity index. figure 6. spga 0/1 response rates through week 52, full analysis set (nri)a weeks 332 332 332 332 332 332 332 332 332 332 330 326 320 324 325 332 166 166 166 166 166 166 166 145 145 144 144 145 142 144 145 145 0 10 20 30 40 50 60 sp g a 0 /1 r es po n se r at e, % o f pa ti en ts 70 80 90 100 0 1 2 4 8 12 16 primary endpoint 20 24 28 32 36 40 44 48 52 53.6% 52.7% 7.2% 53.8% deucravacitinib patients, n placebo – deucravacitinib deucravacitinib placebo → deucravacitinib apatients who missed efficacy assessments due to covid-19 were excluded from efficacy analyses at those time points. nri, nonresponder imputation; spga 0/1, static physician’s global assessment score of 0 (clear) or 1 (almost clear) with a ≥2-point improvement from baseline. figure 7. spga 0/1 response rates through week 52 in systemic treatment-naive, prior systemic treatment, and prior oral systemic treatment patients (nri)a 0 10 20 30 40 50 60 sp g a 0 /1 r es po n se r at e, % o f pa ti en ts 70 80 90 100 0 1 2 4 8 12 16 primary endpoint 20 weeks systemic treatment naive 24 28 32 36 40 44 48 52 132 132 132 132 132 132 132 132 132 132 132 127 122 127 129 132 57 57 57 57 57 57 57 51 51 51 51 51 50 51 51 51 53.0% 52.3% 5.3% 51.0% 0 10 20 30 40 50 60 sp g a 0 /1 r es po n se r at e, % o f pa ti en ts 70 80 90 100 0 1 2 4 8 12 16 primary endpoint 20 weeks prior systemic treatment 24 28 32 36 40 44 48 52 200 200 200 200 200 200 200 200 200 200 198 199 198 197 196 200 109 109 109 109 109 109 109 94 94 93 93 94 92 93 94 94 54.0% 53.0% 8.3% 55.3% 0 10 20 30 40 50 60 sp g a 0 /1 r es po n se r at e, % o f pa ti en ts 70 80 90 100 0 1 2 4 8 12 16 primary endpoint 20 weeks prior oral systemic treatment 24 28 32 36 40 44 48 52 114 114 114 114 114 114 114 114 114 114 113 113 113 112 111 114 73 73 73 73 73 73 73 65 65 65 65 65 65 65 65 65 50.9% 57.0% 9.6% 53.8% deucravacitinib placebo → deucravacitinib deucravacitinib patients, n placebo – deucravacitinib deucravacitinib patients, n placebo – deucravacitinib deucravacitinib patients, n placebo – deucravacitinib apatients who missed efficacy assessments due to covid-19 were excluded from efficacy analyses at those time points. nri, nonresponder imputation; spga 0/1, static physician’s global assessment score of 0 (clear) or 1 (almost clear) with a ≥2-point improvement from baseline. figure 8. spga 0/1 response rates through week 52 in biologic treatment-naive and prior biologic treatment patients (nri)a 50.0% 45.5% 47.7% 0 10 20 30 40 50 60 sp g a 0 /1 r es po n se r at e, % o f pa ti en ts 70 80 90 100 0 1 2 4 8 12 16 primary endpoint 20 weeks 24 28 32 36 40 44 48 52 130 130 130 130 130 130 130 130 130 130 128 129 128 129 129 130 63 63 63 63 63 63 63 55 55 54 54 55 53 54 55 55 55.9% 55.9% 58.9% 0 10 20 30 40 50 60 sp g a 0 /1 r es po n se r at e, % o f pa ti en ts 70 80 90 100 0 1 2 4 8 12 16 primary endpoint 20 weeks biologic treatment naive prior biologic treatment 24 28 32 36 40 44 48 52 202 202 202 202 202 202 202 202 202 202 202 197 192 195 196 202 103 103 103 103 103 103 103 90 90 90 90 90 89 90 90 90 7.8% deucravacitinib placebo → deucravacitinib deucravacitinib patients, n placebo – deucravacitinib deucravacitinib patients, n placebo – deucravacitinib 6.3% apatients who missed efficacy assessments due to covid-19 were excluded from efficacy analyses at those time points. nri, nonresponder imputation; spga 0/1, static physician’s global assessment score of 0 (clear) or 1 (almost clear) with a ≥2-point improvement from baseline. disclosures • jb: research funds payable to the psoriasis treatment center of new jersey: abbvie, amgen, arcutis, boehringer ingelheim, bristol myers squibb, celgene, corevitas' (corrona) psoriasis registry, dermavant, dermira/ucb, eli lilly, glenmark, janssen biotech, kadmon, leo pharma, lycera, menlo therapeutics, novartis, pfizer, regeneron, sun pharma, taro, and valeant; consultant: abbvie, amgen, celgene, eli lilly, janssen biotech, novartis, sun pharma, and valeant; speaker: abbvie, celgene, eli lilly, janssen biotech, and novartis • awa: grants and personal fees: abbvie, bristol myers squibb, eli lilly, janssen, leo pharma, and novartis; personal fees: boehringer ingelheim/parexel, celgene, dermavant, genentech, glaxosmithkline, menlo therapeutics, merck, modernizing medicine, ortho dermatologics, pfizer, regeneron, sanofi genzyme, science 37, sun pharma, and valeant; grants: dermira, kyowa hakko, and ucb, outside the submitted work • rbw: research grants: abbvie, almirall, amgen, celgene, eli lilly, janssen, leo pharma, novartis, pfizer, and ucb; consulting fees: abbvie, almirall, amgen, biogen, boehringer ingelheim, celgene, dice therapeutics, eli lilly, janssen, leo pharma, novartis, pfizer, sanofi, ucb, and union • kap: consultant: abbvie, acelyrin, akros, amgen, aralez, arcutis, avillion, bausch health/valeant, boehringer ingelheim, bristol myers squibb, can-fite biopharma, celgene, celltrion, coherus, dermavant, dermira, dice therapeutics, dow pharma, eli lilly, evelo biosciences, forbion, galderma, incyte, janssen, kyowa hakko, leo pharma, meiji seika pharma, merck (msd), mitsubishi pharma, novartis, pfizer, regeneron, reistone, roche, sanofi aventis/genzyme, sandoz, sun pharma, takeda, ucb, vtv therapeutics, and xencor; speakers bureau: abbvie, amgen, bausch health/valeant, celgene, eli lilly, galderma, incyte, janssen, kyowa hakko, leo pharma, merck (msd), novartis, pfizer, and sanofi aventis/genzyme; clinical research grants: abbvie, akros, amgen, anacor, arcutis, avillion, bausch health/valeant, boehringer ingelheim, bristol myers squibb, can-fite biopharma, celgene, coherus, dermavant, dermira, dice therapeutics, dow pharma, eli lilly, evelo biosciences, galderma, gilead, glaxosmithkline, incyte, janssen, kyowa hakko, leo pharma, merck (msd), novartis, pfizer, regeneron, roche, sanofi aventis/genzyme, sun pharma, takeda, and ucb; honoraria: abbvie, acelyrin, akros, amgen, aralez, bausch health/valeant, boehringer ingelheim, celgene, celltrion, coherus, dermavant, dice therapeutics, eli lilly, forbion, galderma, janssen, kyowa hakko, leo pharma, meiji seika pharma, merck (msd), mitsubishi pharma, novartis, pfizer, reistone, sanofi aventis/genzyme, sandoz, sun pharma, takeda, ucb, vtv therapeutics, and xencor; scientific officer: akros, anacor, arcutis, dice therapeutics, and kyowa hakko; steering committees: abbvie, amgen, bausch health/valeant, boehringer ingelheim, celgene, eli lilly, janssen, kyowa hakko, merck (msd), novartis, pfizer, regeneron, reistone, and sanofi aventis/genzyme; advisory boards: abbvie, amgen, bausch health/valeant, boehringer ingelheim, bristol myers squibb, celgene, dice therapeutics, dow pharma, eli lilly, galderma, janssen, merck (msd), novartis, pfizer, regeneron, sanofi aventis/genzyme, sun pharma, and ucb • dt: grant/research support, consultant, scientific advisory board, and speakers bureau: abbvie, almirall, amgen, biogen idec, boehringer ingelheim, bristol myers squibb, eli lilly, galapagos, galderma, janssen-cilag, leo pharma, novartis, pfizer, regeneron, roche, sandoz-hexal, sanofi, target-solution, and ucb • am: advisory boards: abbvie, amgen, boehringer ingelheim, janssen biotech, and leo pharma; consulting fees: abbvie, amgen, eli lilly, janssen biotech, leo pharma, novartis, sun pharma, and ucb; honoraria: abbvie, amgen, boehringer ingelheim, eli lilly, janssen biotech, leo pharma, novartis, sun pharma, and ucb; investigator: abbvie, amgen, boehringer ingelheim, celgene, eli lilly, janssen biotech, leo pharma, merck, novartis, sun pharma, and ucb; research grants: abbvie, amgen, boehringer ingelheim, celgene, janssen biotech, leo pharma, merck, and sun pharma; speaker: abbvie, amgen, janssen biotech, leo pharma, sun pharma, and ucb • jc: clinical trials: abbvie, amgen, bristol myers squibb, chemocentryx, eli lilly, galderma, janssen, sun pharma, and ucb; consulting fees: abbvie, amgen, bristol myers squibb, dermavant, eli lilly, and sanofi genzyme; speakers bureau: amgen, abbvie, and eli lilly • ma: advisory boards: abbvie, amgen, boehringer ingelheim, janssen biotech, and leo pharma; consulting fees: abbvie, amgen, eli lilly, janssen biotech, leo pharma, novartis, sun pharma, and ucb; honoraria: abbvie, amgen, boehringer ingelheim, eli lilly, janssen biotech, leo pharma, novartis, sun pharma, and ucb; investigator: abbvie, amgen, boehringer ingelheim, celgene, eli lilly, janssen biotech, leo pharma, merck, novartis, sun pharma, and ucb; research grants: abbvie, amgen, boehringer ingelheim, celgene, janssen biotech, leo pharma, merck, and sun pharma; speaker: abbvie, amgen, janssen biotech, leo pharma, sun pharma, and ucb • lh and cd: employees and shareholders: bristol myers squibb • cemg: honoraria and/or research grants: abbvie, almirall, amgen, anaptysbio, bristol myers squibb, eli lilly, glaxosmithkline, janssen, leo pharma, novartis, sanofi, and ucb conclusions • deucravacitinib-treated patients from the poetyk pso-1 trial maintained response rates for pasi 75 and spga 0/1 through week 52, regardless of prior treatment exposure to biologic, systemic nonbiologic, and/or oral systemic agents • patients who switched from placebo to deucravacitinib at week 16 also showed robust responses at week 52 on both endpoints and across subgroups • these analyses support the efficacy of deucravacitinib in moderate to severe psoriasis regardless of prior treatment history references 1. sotyktu™ (deucravacitinib) [package insert]. princeton, nj: bristol-myers squibb company; september 2022. 2. burke jr, et al. sci transl med. 2019;11:eaaw1736. 3. wrobleski st, et al. j med chem. 2019;62:8973-8995. 4. armstrong aw, et al. j am acad dermatol. 2023;88:29-39. 5. warren rb, et al. presented at the 30th eadv congress, september 29–october 2, 2021. late breaker. 6. warren rb, et al. presented at the 30th eadv congress, september 29–october 2, 2021. 7. warren rb, et al. presented at the eadv spring symposium; may 12–14, 2022. acknowledgments • this study was sponsored by bristol myers squibb • writing and editorial assistance was provided by liz rockstein, phd, of peloton advantage, llc, an open health company, parsippany, nj, usa, funded by bristol myers squibb figure 1. mechanism of action of deucravacitinib tyk2 deucravacitinib (allosteric inhibitor class) unique regulatory domain catalytic domain (highly conserved across jak family) atp-binding active site (approved jak inhibitor class) •  ≥100-fold greater selectivity for tyk2 vs jak 1/3 • ≥2000-fold greater selectivity for tyk2 vs jak 2 selectivity in cells2,3: atp, adenosine 5′-triphosphate; jak, janus kinase; tyk2, tyrosine kinase 2. mailto:dreamacres1%40icloud.com?subject= deucravacitinib in plaque psoriasis: 2-year laboratory results from the phase 3 poetyk pso program neil j korman,1 thierry passeron,2 kenneth b gordon,3 yukari okubo,4 jerry bagel,5 howard sofen,6 richard b warren,7 neal bhatia,8 lynda spelman,9 kevin winthrop,10 lauren hippeli,11 renata m kisa,11 subhashis banerjee,11 diamant thaçi12 1case western reserve university, university hospitals of cleveland, cleveland, oh, usa; 2côte d’azur university, university hospital of nice, nice, france; 3medical college of wisconsin, milwaukee, wi, usa; 4tokyo medical university, tokyo, japan; 5psoriasis treatment center of new jersey, east windsor, nj, usa; 6ucla school of medicine, los angeles, ca, usa; 7dermatology centre, salford royal nhs foundation trust, nihr manchester biomedical research centre, the university of manchester, manchester, uk; 8therapeutics clinical research, san diego, ca, usa; 9veracity clinical research, brisbane, qld, australia; 10oregon health & science university, portland, or, usa; 11bristol myers squibb, princeton, nj, usa; 12university of lübeck, lübeck, germany presented at the winter clinical dermatology conference hawaii®; january 13-18, 2023; kohala coast, hi this is an encore of the 2022 31st eadv congress presentation email: neil.korman@uhhospitals.org copies of this poster are for personal use only and may not be reproduced without written permission from the authors. synopsis • tyrosine kinase 2 (tyk2) is an intracellular enzyme that mediates signaling of cytokines (interleukin-23 and type i interferons) involved in psoriasis pathogenesis1 • deucravacitinib, an oral, selective, allosteric tyk2 inhibitor, is approved by the us food and drug administration for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy2 • deucravacitinib has a unique mechanism of action, the first in a new class of small molecules1 (figure 1) • the selectivity of deucravacitinib facilitates a more targeted therapeutic approach that avoids signature laboratory changes seen with the janus kinase (jak) 1/2/3 inhibitors — in phase 2 and phase 3 trials (poetyk pso-1 and pso-2) in plaque psoriasis, deucravacitinib treatment did not result in neutropenia, elevated liver enzyme and serum creatinine levels, and dyslipidemia — adverse events that have been associated with jak 1/2/3 inhibitors3-7 • deucravacitinib demonstrated a robust efficacy profile, including superiority to placebo and apremilast and durability and maintenance of response, in 2 multinational phase 3 trials in patients with moderate to severe plaque psoriasis5,6,8 • patients who completed the poetyk pso-1 and pso-2 trials could enroll in the ongoing poetyk long-term extension (lte) trial objectives • to determine whether there were any clinically relevant changes in blood laboratory parameters with up to 2 years of deucravacitinib treatment in the poetyk pso-1, pso-2, and lte trials • to evaluate whether deucravacitinib treatment elicits changes in the blood that are known to occur with jak 1/2/3 inhibitors methods study designs • poetyk pso-1 (nct03624127) and pso-2 (nct03611751) were 52-week, multinational, phase 3, double-blind trials that randomized patients with moderate to severe plaque psoriasis 2:1:1 to deucravacitinib 6 mg once daily, placebo, or apremilast 30 mg twice daily (figure 2) • at week 52, eligible patients were able to enroll in the poetyk lte trial (nct04036435) and receive open-label deucravacitinib 6 mg once daily for up to 2 years figure 2. poetyk pso-1, pso-2, and lte study designs 100 poetyk pso-1 and pso-2 deucravacitinib 6 mg qdplacebo (n = 166) deucravacitinib 6 mg qd apremilast 30 mg bid titrate*p o e t y k p so -1 1 :2 :1 r an d o m iz at io n deucravacitinib 6 mg qd (n = 332) apremilast 30 mg bida (n = 168) deucravacitinib 6 mg qdplacebo (n = 255) deucravacitinib 6 mg qd (n = 511) deucravacitinib 6 mg qd<pasi 75 deucravacitinib 6 mg qd<pasi 75 deucravacitinib 6 mg qd apremilast 30 mg bida (n = 254) p o e t y k p so -2 1 :2 :1 r an d o m iz at io n cumulative exposure (weeks) exposure relative to lte(weeks) 16 24 520 1 :1 deucravacitinib 6 mg qdplacebob deucravacitinib 6 mg qdplacebob primary endpoint b li n d e d s w it c h t o o p e n -l a b e l d e u c r a v a c it in ib open-label deucravacitinib 6 mg qd (n = 1221) poetyk lte 14856 60 68 76 88 112 124 1364 8 12 20 28 32 36 40 44 48 480 964 8 16 24 36 60 72 84 ≥pasi 75 ≥pasi 75 <pasi 50 ≥pasi 50 safety assessed for all available data (currently 2 years)c poetyk pso-1: from armstrong aw, et al. deucravacitinib versus placebo and apremilast in moderate to severe plaque psoriasis: efficacy and safety results from the 52-week, randomized, double-blinded, placebo-controlled phase 3 poetyk pso-1 trial. j am acad dermatol. 2023;88:29-39. this work is licensed under a creative commons attribution license (cc by-nc-nd 4.0). https://creativecommons.org/licenses/by-nc-nd/4.0/. poetyk pso-2: from strober b, et al. deucravacitinib versus placebo and apremilast in moderate to severe plaque psoriasis: efficacy and safety results from the 52-week, randomized, double-blinded, phase 3 poetyk pso-2 trial. j am acad dermatol. 2023;88:40-51. this work is licensed under a creative commons attribution license (cc by-nc-nd 4.0). https://creativecommons.org/licenses/by-nc-nd/4.0/. aapremilast was titrated from 10 mg qd to 30 mg bid over the first 5 days of dosing. bupon relapse (≥50% loss of week 24 pasi percentage improvement from baseline), patients were to be switched to deucravacitinib 6 mg qd. cdata reported through the cutoff date of october 1, 2021. bid, twice daily; lte, long-term extension; pasi, psoriasis area and severity index; pasi 50, ≥50% reduction from baseline in pasi; pasi 75, ≥75% reduction from baseline in pasi; qd, once daily. laboratory assessments • pooled poetyk pso-1 + pso-2 data over weeks 0–52 and pooled poetyk pso-1 + pso-2 + lte data over weeks 0–100 are presented • changes in laboratory parameters that are known to be affected by jak 1/2/3 inhibitors3 were evaluated in blood over time — hematologic parameters: lymphocytes, neutrophils, platelets, and hemoglobin — lipid parameter: total cholesterol — chemistry parameters: creatinine, creatine phosphokinase (cpk), and alanine aminotransferase (alt) • incidences of grade ≥3 laboratory abnormalities (common terminology criteria for adverse events [ctcae] version 5.0) and treatment discontinuations due to laboratory abnormalities were also evaluated through week 100 results patient population • this analysis included 1519 patients who received ≥1 dose of deucravacitinib in poetyk pso-1, pso-2, and/or the lte through the data cutoff date of october 1, 2021 — total deucravacitinib exposure was 2482.0 person-years (py) • in total, 1179 (77.6%) and 584 (38.4%) patients had ≥52 weeks and ≥104 weeks, respectively, of continuous deucravacitinib exposure at the data cutoff date — median duration of exposure was 682.0 days (97 weeks) • baseline patient demographics and disease characteristics are presented in table 1 laboratory assessments • no clinically meaningful changes were observed over weeks 0–100 in any of the evaluated laboratory parameters in the pooled poetyk pso-1/pso-2/lte population (figure 3) — laboratory parameters remained within normal ranges for most patients throughout this period • grade ≥3 laboratory abnormalities were rare (table 2) — frequencies of individual events were comparable across groups over the first 52 weeks (poetyk pso-1 and pso-2), and no increases were seen with deucravacitinib treatment through week 100 in the poetyk lte — grade ≥3 cpk elevations occurred rarely, were mostly transient, and were observed at a similar incidence in each treatment group over the first 52 weeks; almost all were related to recent physical exertion, and none was serious • discontinuations due to laboratory abnormalities were low and balanced across treatment groups over the first 52 weeks and were also low through week 100 in the poetyk lte (table 3) — alt elevations in deucravacitinib-treated patients (table 2) were predominantly transient, and none was serious or resulted in treatment discontinuation figure 3. changes in hematologic, lipid, and chemistry parameters over 2 years in patients receiving deucravacitinib in poetyk pso-1 + pso-2 + lte 0 1 2 3 4 m e an ± s d , 1 0 9 /l 5 lymphocytes n= 0 2 4 6 m e an ± s d , 1 0 9 /l 8 neutrophils n= 0 100 200 250 150 300 350 400 450 500 m e an ± s d , 1 0 9 /l platelets 4 8 12 2016 2824 32 444036 48 5652 6460 68 7672 8480 88 92 10096 104 0 4 8 12 2016 2824 32 444036 48 5652 6460 68 7672 8480 88 92 10096 104 0 4 8 12 2016 2824 32 444036 48 5652 6460 68 7672 8480 88 92 10096 104 0 4 8 12 2016 2824 32 444036 48 5652 6460 68 7672 8480 88 92 10096 104 0 4 8 12 2016 2824 32 444036 48 5652 6460 68 7672 8480 88 92 10096 104 0 4 8 12 2016 2824 32 444036 48 5652 6460 68 7672 8480 88 92 10096 104 0 8 16 24 32 40 48 5652 64 72 80 88 10096 104 0 4 8 12 2016 2824 32 444036 48 5652 start of lte start of lte 6460 68 7672 8480 88 92 10096 104 lln uln lln uln lln uln n= 7841517 747769 10301075742 113294294695996698810281028 1164 1133 1132 1097 1036 8021519 764793 10611094757 1146963971959989101510511051 1179 1148 1151 1112 1050 8021519 764793 10611094757 1146963972977989101310481050 1178 1148 1151 1112 1050 8031519 765793 10671097758 1146968974982992101610511055 1180 1158 1151 1114 1051 7971518 753779 10381081747 114495095896897099910351038 1170 1146 1141 1108 1048 7921518 750775 10251076739 113994294996296699210311031 1168 1140 1136 1098 1042 1519 790 1064742 962 1042 7921518 750775 10251076739 113994294996296699210311031 1168 1140 1136 1098 1042 12 1.5 1.0 0.5 60 40 20 0 13 14 15 16 17 18 m e an ± s d , g/ d l hemoglobin n= m e an ± s d , m g/ d l total cholesterol n= m e an ± s d , m g/ d l creatinine n= 0 250 500 750 m e an ± s d , u /l 1000 100 150 200 250 300 cpk n= m e an ± s d , u /l alt n= lln uln lln uln lln uln lln uln lln uln alt, alanine aminotransferase; cpk, creatine phosphokinase; lln, lower limit of normal; lte, long-term extension; sd, standard deviation; uln, upper limit of normal. table 2. ctcae grades 3 and 4 abnormalities in laboratory parameters over 1 and 2 years at 1 year (poetyk pso-1 + pso-2, weeks 0–52) at 2 years (poetyk pso-1 + pso-2 + lte, weeks 0–100) placebo (n = 666) deucravacitinib (n = 1364) apremilast (n = 422) deucravacitinib (n = 1519) parameter grade baseline n (%) week 52 n (%) baseline n (%) week 52 n (%) baseline n (%) week 52 n (%) baseline n (%) week 100 n (%) lymphocyte count decreased 3 0 1 (0.2)a 0 2 (0.1)b 0 1 (0.2)c 0 2 (0.1)d 4 0 0 0 0 0 0 0 0 neutrophil count decreased 3 0 1 (0.2)a 1 (0.1)b 4 (0.3)b 0 0 1 (0.1)d 5 (0.3)d 4 0 1 (0.2)a 0 0 0 1 (0.2)c 0 1 (0.1)d platelet count decreased 3 0 1 (0.2)e 0 0 0 0 0 0 4 0 0 0 0 0 0 0 0 anemia 3 0 0 0 0 0 1 (0.2)c 0 1 (0.1)d 4 0 0 0 0 0 0 0 0 high cholesterol 3 0 0 0 1 (0.1)f 0 0 0 1 (0.1)g 4 0 0 0 0 0 0 0 0 creatinine increased 3 0 0 0 0 0 0 0 0 4 0 0 0 0 0 0 0 0 cpk increased 3 1 (0.2)a 4 (0.6)a 3 (0.2)b 19 (1.4)b 1 (0.2)h 7 (1.7)h 3 (0.2)i 25 (1.7)i 4 0 3 (0.5)a 0 13 (1.0)b 0 1 (0.2)h 0 26 (1.7)i alt increased 3 2 (0.3)a 0 1 (0.1)b 4 (0.3)b 0 0 1 (0.1)i 10 (0.7)i 4 0 0 0 0 0 0 0 0 an = 658. bn = 1351. cn = 418. dn = 1503. en = 657. fn = 1317. gn = 1454. hn = 419. in = 1504. alt, alanine aminotransferase; cpk, creatine phosphokinase; ctcae, common terminology criteria for adverse events; lte, long-term extension. table 3. laboratory abnormality adverse events leading to treatment discontinuation over 1 and 2 years at 1 year (poetyk pso-1 + pso-2, weeks 0–52) at 2 years (poetyk pso-1 + pso-2 + lte, weeks 0–100) placebo (n = 666) total exposure = 240.9 py deucravacitinib (n = 1364) total exposure = 969.0 py apremilast (n = 422) total exposure = 221.1 py deucravacitinib (n = 1519) total exposure = 2482.0 py parameter n (%) eair/100 py n (%) eair/100 pya n (%) eair/100 pya n (%) eair/100 pya lymphopenia 0 0 1 (0.1) 0.1 0 0 1 (0.1) 0.0 blood cpk increased 0 0 2 (0.1) 0.2 1 (0.2) 0.4 3 (0.2) 0.1 hepatic function abnormal 1 (0.2)b 0.4 1 (0.1)c 0.1 0 0 1 (0.1) 0.0 ast increased 0 0 0 0 1 (0.2) 0.4 0 0 aincidences are expressed as eairs per 100 py to account for variable exposure due to treatment switches at weeks 16 and 24. bpatient who received placebo during weeks 0–16 had alt >3x uln on days 1 and 8; total bilirubin levels remained in the normal range. the patient discontinued placebo and alt levels improved. cpatient who received deucravacitinib during weeks 0–16 had alt and ast elevations ≥3x uln and bilirubin elevation >2x uln on day 58. deucravacitinib treatment was discontinued and alt, ast, and bilirubin levels improved. alt, alanine aminotransferase; ast, aspartate aminotransferase; cpk, creatine phosphokinase; eair, exposure-adjusted incidence rate; lte, long-term extension; py, person-years; uln, upper limit of normal. conclusions • in the large, phase 3 poetyk pso-1, pso-2, and lte trials in patients with plaque psoriasis, no trends or clinically meaningful changes in multiple hematologic, lipid, and chemistry parameters were observed in 1519 patients with 2482.0 py of deucravacitinib exposure — signature laboratory changes associated with jak 1/2/3 inhibitors were not observed over 2 years of deucravacitinib exposure • ctcae grade ≥3 laboratory abnormalities and treatment discontinuations due to laboratory abnormalities in deucravacitinib-treated patients were rare, and were comparable to incidence rates observed with placebo and apremilast over the first 52 weeks • deucravacitinib, a once-daily oral drug, has the potential to become a treatment of choice and new standard of care for patients who require systemic therapy for their moderate to severe plaque psoriasis references 1. burke jr, et al. sci transl med. 2019;11:eaaw1736. 2. sotyktu™ (deucravacitinib) [package insert]. princeton, nj: bristol-myers squibb company; september 2022. 3. papp k, et al. n engl j med. 2018;379:1313-1321. 4. winthrop kl. nat rev rheumatol. 2017; 13:234-243. 5. armstrong aw, et al. j am acad dermatol. 2023;88:29-39. 6. strober b, et al. j am acad dermatol. 2023;88:40-51. 7. thaçi d, et al. presented at the 30th eadv congress; september 29–october 2, 2021. 8. warren rb, et al. presented at the eadv spring symposium; 12–14 may 2022; ljubljana, slovenia. 9. wrobleski st, et al. j med chem. 2019;62:8973-8995. acknowledgments • this study was sponsored by bristol myers squibb • writing and editorial assistance was provided by liz rockstein, phd, of peloton advantage, llc, an open health company, parsippany, nj, usa, funded by bristol myers squibb disclosures • njk: advisory board and consulting fees: abbvie, boehringer ingelheim, bristol myers squibb, celgene, eli lilly, janssen, leo pharma, novartis, principia, regeneron, sanofi genzyme, sun pharma, and ucb; grant support/principal investigator: abbvie, amgen, argenx, bristol myers squibb, celgene, chemocentryx, eli lilly, galderma, kyowa kirin, leo pharma, menlo, principia, prothena, rhizen, syntimmune, trevi, and xbiotech; speaker: abbvie, eli lilly, janssen, novartis, regeneron, and sanofi genzyme • tp: advisory board and consulting fees: abbvie, almirall, amgen, boehringer ingelheim, bristol myers squibb, celgene, eli lilly, galderma, incyte, janssen, leo pharma, novartis, pfizer, sanofi genzyme, sun pharma, and ucb • kbg: grant support and consulting fees: abbvie, boehringer ingelheim, bristol myers squibb, celgene, eli lilly, janssen, novartis, and ucb; consulting fees: almirall, amgen, dermira, leo pharma, pfizer, and sun pharma • yo: research grants: eisai, maruho, shiseido, and torii; current consulting/advisory board agreements: abbvie, amgen, boehringer ingelheim, bristol myers squibb, eli lilly, janssen, and sun pharma; speakers bureau: abbvie, amgen, boehringer ingelheim, bristol myers squibb, celgene, eisai, eli lilly, janssen pharma, jimro, kyowa kirin, leo pharma, maruho, novartis, pfizer, sanofi, sun pharma, taiho, tanabe-mitsubishi, torii, and ucb; clinical trials: abbvie, amgen, boehringer ingelheim, bristol myers squibb, celgene, eli lilly, janssen, leo pharma, maruho, pfizer, sun pharma, and ucb • jb: research funds payable to the psoriasis treatment center of new jersey: abbvie, amgen, arcutis, boehringer ingelheim, bristol myers squibb, celgene, corevitas’ (corrona) psoriasis registry, dermavant, dermira/ucb, eli lilly, glenmark, janssen biotech, kadmon, leo pharma, lycera, menlo therapeutics, novartis, pfizer, regeneron, sun pharma, taro, and valeant; consultant: abbvie, amgen, celgene, eli lilly, janssen biotech, novartis, sun pharma, and valeant; speaker: abbvie, celgene, eli lilly, janssen biotech, and novartis • hs: clinical investigator: abbvie, amgen, boehringer ingelheim, bristol myers squibb, eli lilly, janssen, leo pharma, novartis, and sun pharma • rbw: research grants: abbvie, almirall, amgen, celgene, eli lilly, janssen, leo pharma, novartis, pfizer, and ucb; consulting fees: abbvie, almirall, amgen, biogen, boehringer ingelheim, celgene, dice therapeutics, eli lilly, janssen, leo pharma, novartis, pfizer, sanofi, ucb, and union • nb: advisor and consultant investigator: abbvie, almirall, arcutis, arena, boehringer ingelheim, bristol myers squibb, dermavant, incyte, isdin, johnson & johnson, leo pharma, lilly, ortho, pfizer, regeneron, sanofi, stemline, and sun pharma; investigator: arcutis, biofrontera, boehringer ingelheim, bristol myers squibb, dermavant, galderma, leo pharma, lilly, and ortho • ls: consultant, paid investigator, and/or speaker: abbvie, amgen, anacor, ascend, astellas, astrazeneca, blaze bioscience, bristol myers squibb, boehringer ingelheim, botanix, celgene, dermira, eli lilly, galderma, genentech, glaxosmithkline, hexima, janssen, leo pharma, mayne, medimmune, merck, merck-serono, novartis, otsuka, pfizer, phosphagenics, photon md, regeneron, roche, samumed, sanofi genzyme, shr, sun pharma anz, trius, ucb, and zai lab • kw: consulting: abbvie, astrazeneca, bristol myers squibb, eli lilly, galapagos, gilead, glaxosmithkline, novartis, pfizer, regeneron, roche, sanofi, and ucb; research: bristol myers squibb and pfizer • lh, rmk, and sb: employees and shareholders: bristol myers squibb • dt: grant/research support, consultant, scientific advisory board, and speakers bureau: abbvie, almirall, amgen, biogen idec, boehringer ingelheim, bristol myers squibb, eli lilly, galapagos, galderma, janssen-cilag, leo pharma, novartis, pfizer, regeneron, roche, sandoz-hexal, sanofi, target-solution, and ucb figure 1. mechanism of action of deucravacitinib • ≥100-fold greater selectivity for tyk2 vs jak 1/3 • ≥2000-fold greater selectivity for tyk2 vs jak 2 deucravacitinib (allosteric inhibitor class) unique tyk2 regulatory domain catalytic domain (highly conserved across jak family) atp-binding active site (approved jak inhibitor class) tyk2 selectivity in cells1,9: atp, adenosine 5′-triphosphate; jak, janus kinase; tyk2, tyrosine kinase 2. table 1. baseline patient demographics and disease characteristics parameter poetyk pso-1 + pso-2 + lte deucravacitinib (n = 1519) age, mean (sd), y 46.6 (13.4) weight, mean (sd), kg 90.6 (21.6) body mass index, mean (sd), kg/m2 30.5 (6.8) female, n (%) 493 (32.5) race, n (%) white 1325 (87.2) asian 153 (10.1) black or african american 23 (1.5) other 18 (1.2) age at disease onset, mean (sd), y 28.8 (14.9) disease duration, mean (sd), y 18.7 (12.7) pasi, mean (sd) 21.1 (8.1) spga, n (%) 3 (moderate) 1211 (79.7) 4 (severe) 308 (20.3) bsa involvement, mean (sd), % 26.2 (15.8) bsa, body surface area; lte, long-term extension; pasi, psoriasis area and severity index; sd, standard deviation; spga, static physician’s global assessment. microsoft word july 2020 bar 835 proof returned.docx skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 357 brief articles photodynamic therapy with δ-aminolevulinic acid and blue light for the treatment of actinic cheilitis joan paul, md, mph1, alicia t. dagrosa, md, mba2, youdinghuan chen, phd3, pamela gangar, md4, daniel r. ressler5, m. shane chapman, md, mba2 1the permanente medical group, department of dermatology, oakland, ca 2dartmouth-hitchcock medical center, department of dermatology, lebanon, nh 3dartmouth geisel school of medicine, department of epidemiology, hanover, nh 4university of arizona, department of pediatrics, tucson, az 5dartmouth-hitchcock medical center, clinical research unit, lebanon, nh background: actinic cheilitis is a common precancerous disorder of the lower lip caused by ultraviolet radiation. photodynamic therapy (pdt) is a potential treatment for actinic cheilitis, however controlled clinical trials regarding this treatment are needed. objective: to evaluate the safety and efficacy of pdt with blue light and topical δaminolevulinic acid (levulan®) in the treatment of actinic cheilitis. methods: we conducted a single center, investigator-initiated, nonrandomized, open-label, proof of concept study of pdt with blue light for the treatment of actinic cheilitis. we enrolled 24 subjects, 20 meeting inclusion and exclusion criteria. one subject withdrew from the study prior to treatment. the study consisted of a screening visit, one to three scheduled treatments, and two follow-up visits. the primary outcome was clinical improvement in actinic cheilitis from baseline, estimated as no (0%), mild (25%), moderate (50%), marked (75%), or excellent improvement (100%). post-treatment assessment of swelling, erythema, flaking/scaling, crusting, vesiculation/pustulation, and erosion/ulceration was also recorded. subjects completed the dermatological life quality index questionnaire, subject global assessment of improvement, and pain assessment at each visit. results: 65% of subjects achieved clinical improvement of 75% or greater and 20% achieved 100% improvement by the end of the study. treatments were well tolerated with minimal discomfort. subjects experienced transient mild adverse effects. conclusion: overall, our study supports using pdt for the treatment of actinic cheilitis. abstract skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 358 actinic cheilitis is a common precancerous manifestation of severe photodamage of the lower lip caused by chronic ultraviolet radiation.1,2 conventional therapies, such as cryotherapy, topical 5-fluorouracil or imiquimod, chemical peels, electrodesiccation, laser ablation, and vermillionectomy are accepted treatments.3 however, they can be expensive or timeconsuming, can require local or general anesthesia, and can be associated with noncompliance, high recurrence rates, or scars. alternative treatments for actinic cheilitis would be helpful. several reports have shown photodynamic therapy (pdt) to be an effective treatment of actinic cheilitis requiring relatively few pdt treatments and causing minimal cutaneous side effects.2,4,5 pdt is based on the combined use of photosensitizers and photoradiation. topically applied δaminolevulinic acid (ala) is theorized to be taken up by premalignant cells. upon irradiation with a light source, photoactivated porphyrins produce singlet oxygen and other potent oxidizers, resulting in cell death.2,6,7,8 unfortunately, controlled clinical trials assessing the efficacy of pdt for actinic cheilitis are lacking. we hypothesized that using pdt with blue light and topical ala treatment is a safe and effective treatment for actinic cheilitis. we conducted a single center, investigator initiated, nonrandomized, open-label, proof of concept study of pdt with blue light and topical ala in the treatment of actinic cheilitis. we sought to enroll a total of 20 subjects in the study. the study was approved by our institutional review board. subject recruitment patients at least 18 years of age from the outpatient dermatology clinic with a clinical diagnosis of actinic cheilitis were invited to participate in the study. exclusion criteria included active herpes labialis lesions, pregnancy or lactation, and use of any treatment for actinic cheilitis within 3 months of study entry. visit schedule the study consisted of a screening visit, up to 3 scheduled treatments 6 weeks apart, and 2 follow-up office visits 12 and 24 weeks after the final treatment. total study duration was approximately 36 weeks. treatments were discontinued once the patient achieved clinical clearance. study medication application, blue light therapy, post-therapy assessments, tolerability assessments, and photographs were performed at each visit. treatment parameters levulan® kerastick® (supplied by dusa pharmaceuticals, inc.) containing 354 milligrams of aminolevulinic acid hcl at 20% concentration was applied topically to the precleaned designated treatment area. after an incubation period of 90 minutes, the area was cleaned, and blu-u® blue light (417 nanometers) was administered to the target area for 16 minutes and 40 seconds, resulting in approximately 10 j/cm2 delivered at 10 mw/cm2. subjects were given post-treatment instructions on aftercare (gentle cleansing, petrolatum application, and sun protection for at least 48 hours after each treatment). outcomes the primary outcome was assessed by the investigators as clinical improvement in actinic cheilitis from baseline to the end of the study (approximately week 36) and was estimated as none (0%), mild (25%), moderate (50%), marked (75%), or excellent (100%). posttreatment investigator assessments of swelling, erythema, flaking/scaling, crusting, vesiculation/pustulation, and introduction methods skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 359 erosion/ulceration were graded on a scale of 0 to 4 (none, mild, moderate, severe). adverse events were assessed at every visit. subjects completed the dermatological life quality index (dlqi) questionnaire every visit except during screening.9 the subject global assessment was also performed to assess the subjects’ impression of their overall improvement as compared to baseline, defined as none (0%), mild (25%), moderate (50%), marked (75%), and excellent (100%). pain was assessed at each treatment visit using a visual analogue scale (vas) from 0 to 10, 0 indicating no pain and 10 indicating the worst possible pain. two days after each treatment, patients were contacted by telephone and asked to assess redness, swelling, and dryness (graded on a scale of 0 to 4). the primary outcome is shown in table 1. of the 20 subjects that participated in the study, 65% achieved clinical improvement of 75% or greater at the end of the study according to the investigators’ assessment. four of these subjects (20%) achieved 100% improvement. five subjects (25%) discontinued the study prior to week 36 one of whom was lost to follow-up before any assessment of clinical improvement was performed. if all available subjects’ results are included in the analysis as of the time of their last assessment, 80% achieved clinical improvement of at least 75%, and five subjects (25%) achieved 100% improvement (mean improvement 75%, standard deviation (sd) 24% for those present for assessment). based on the subjects’ assessment of improvement, 60% achieved improvement of at least 75% by the final assessment. based on a concordance analysis using kappa calculation and mcnemar’s test, investigator and subject assessments of improvement were concordant overall (concordance (kappa) = 0.7814; mcnemar p-value = 0.01431). side effects are depicted in table 2. in general, treatments were well tolerated with minimal discomfort. many subjects had transient side effects including swelling, erythema, and flaking. very few subjects had more serious side effects, such as vesiculation, pustulation, or crusting. no subjects experienced erosion or ulceration. pain during treatment averaged 3.2 on a scale of 0 to 10 (sd 1.8) on the vas. quality of life, as assessed by the dlqi, remained relatively unaffected throughout the study (mean dlqi 0.75, sd 1.29). there were no significant adverse events attributable to participation in the study. table 1. primary outcome: clinical improvement table 2. side effects (graded 0 to 4) overall, our study supports using pdt for the treatment of actinic cheilitis. based on investigator assessment, 65% of subjects discussion results skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 360 had improvement of at least 75% at week 36. eighty percent of subjects (including those that discontinued early) had improvement of at least 75% by the time of their last assessment. treatments were well figure 1. one study subject (a) pre-treatment 1 and (b) 7 weeks post-treatment 3 tolerated with minimal pain and transient side effects; swelling, erythema, and scaling were most common. limitations of this study include its small sample size, lack of blinding or randomization, and a subjective rather than objective (e.g. histological) assessment of outcomes. in conclusion, pdt therapy for actinic cheilitis achieves significant improvement or clearance at 36 weeks. a follow up study to assess recurrence after treatment would be beneficial. conflict of interest disclosures and funding: financial support for the conduction of this study as well as the levulan® kerastick® used in this study was supplied by dusa pharmaceuticals, inc. corresponding author: alicia t. dagrosa, md, mba dartmouth-hitchcock medical center department of dermatology 1 medical center drive lebanon, nh 03756 phone: 603-650-3100 email: alicia.t.dagrosa@hitchcock.org references: 1. soyer hp, rigel ds, mcmeniman e. actinic keratosis, basal cell carcinoma, and squamous cell carcinoma. in: bolognia jl, schaffer jv, cerroni l. dermatology 4th edition. elsevier 2018; 1877-1878. 2. tampa m, sarbu mi, matei c, mitran ci, mitran mi, caruntu c, constantin c, neagu m, georgescu sr. oncology letters. 2019;17:4085-4093. https://doi.org/10.3892/ol.2019.9939 3. salgueiro, a.p., de jesus, l.h., de souza, i.f. et al. treatment of actinic cheilitis: a systematic review. clin oral invest 23, 2041–2053 (2019). 4. ribeiro cf, souza fh, jordão jm, et al. photodynamic therapy in actinic cheilitis: clinical and anatomopathological evaluation of 19 patients. an bras dermatol. 2012;87(3):418-423. 5. zaiac m, clement a. treatment of actinic cheilitis by photodynamic therapy with 5-aminolevulinic acid and blue light activation. j drugs dermatology. 2011;10(11):1240-1245. 6. choudhary s, nouri k, elsaie ml. photodynamic therapy in dermatology: a review. lasers med sci. 2009;24(6):971-980. 7. akimoto m, maeda k, omi t, nishimura t, miyakawa m. photodynamic therapy in the dermatological field and enhanced cutaneous absorption of photosensitizer. prog electromagn res symp cambridge, ma. 2010;session 2a:314. 8. dolmans dejgj, fukumura d, jain rk. photodynamic therapy for cancer. nat rev cancer. 2003;3:380. https://doi.org/10.1038/nrc1071. 9. finlay ay, khan gk. dermatology life quality index (dlqi) a simple practical measure for routine clinical use. clin exp dermatol. 1994;19(3):210-216. acknowledgements: medical writing support was provided by prescott medical communications group (chicago, il) with financial support from ortho dermatologics; ortho dermatologics is a division of bausch health us, llc • presented at winter clinical miami 2023 • february 17-20, 2023 • miami, fl number needed to treat (nnt) what is nnt? � nnt is a metric for quantifying effect sizes of clinically relevant study endpoints1 � nnt represents the number of patients needed to treat to achieve an additional cure in a given timeframe1-3 • for example, nnt=3 means that 3 patients would need to be treated with active drug rather than vehicle before expecting an additional responder2 how is nnt used? � in the absence of head-to-head studies, nnt may be used to indirectly assess comparative efficacy of treatments • evaluation of nnt has been conducted in a variety of therapeutic areas, including psychiatry/neurology, cardiology, oncology, and dermatology � while a clinically relevant nnt threshold has not been established for acne, lower values indicate more favorable treatment (larger effect size) versus vehicle how is nnt calculated? � nnt is the reciprocal of the absolute risk reduction (arr), rounded up to the nearest whole number1-3 what are some limitations of nnt? evaluates one binary outcome (eg, week 12 treatment success)2,4 no consideration of drug tolerability or study design/ population differences1-4 clinical meaning subject to interpretation5 bene�ts of a welldesigned vehicle subtracted from active treatment,a leading to higher nnt values adue to the potential of a well-designed vehicle to result in higher efficacy rates in the control group. benefit of topical combination therapy for acne treatment: analysis of effect size using number needed to treat steven r feldman, md, phd1; george han, md, phd2; valerie callender, md3,4; leon h kircik, md2,5,6; linda stein gold, md7; neal bhatia, md8; stephen k tyring, md, phd9; joshua a zeichner, md2 1wake forest school of medicine, winston-salem, nc; 2icahn school of medicine at mount sinai, new york, ny; 3howard university college of medicine, washington, dc; 4callender dermatology and cosmetic center, glenn dale, md; 5indiana university medical center, indianapolis, in; 6physicians skin care, pllc, dermresearch, pllc, and skin sciences, pllc, louisville, ky; 7henry ford hospital, detroit, mi; 8therapeutics clinical research, san diego, ca; 9university of texas health science center, houston, tx nnts for combination topical acne treatments conclusions � given the paucity of head-to-head studies in acne, nnt may be used as a simple way to compare drug effects across clinical trials � idp-126 gel (clindamycin phosphate 1.2%, bpo 3.1%, adapalene 0.15%) had the most favorable nnt values (lowest), with treatment success rates of ~50% � due to the multifactorial pathogenesis of acne, a triple-combination topical treatment may result in clinical success more often than seen with two-ingredient combination products • these nnt values are supported by phase 2 study results, in which idp-126 led to significantly greater treatment success rates at week 12 compared with its three component dyads in the same vehicle formulation7,8 abbreviations adap, adapalene; bpo, benzoyl peroxide; clin, clindamycin phosphate; egss, evaluator’s global severity scale; iga, investigator’s global assessment; il, inflammatory lesions; nil, noninflammatory lesions; nnt, number needed to treat; tret, tretinoin. references 1. citrome l, ketter ta. int j clin pract. 2013;67(5):407-11. 2. citrome l. j clin psychiatry. 2011;72(3):412-3. 3. manriquez jj, et al. j am acad dermatol. 2007;56(4):664-71. 4. mcalister fa. cmaj. 2008;179(6):549-53. 5. nguyen c, et al. explor res clin soc pharm. 2021;2:100039. 6. drugs@fda: fda-approved drugs. https://www.accessdata.fda.gov/scripts/cder/daf/ 7. stein gold l, et al. presented at the annual american academy of dermatology meeting. march 25-29, 2022. 8. stein gold l, et al. am j clin dermatol. 2022;23(1):93-104. author disclosures srf has received research, speaking and/or consulting support from eli lilly, glaxosmithkline/stiefel, abbvie, janssen, alovtech, vtv therapeutics, bristol-myers squibb, samsung, pfizer, boehringer ingelheim, amgen, dermavant, arcutis, novartis, novan, ucb, helsinn, sun pharma, almirall, galderma, leo pharma, mylan, celgene, ortho dermatologics menlo, merck & co, qurient, forte, arena, biocon, accordant, argenx, sanofi, regeneron, the national biological corporation, caremark, teladoc, eurofins, informa, uptodate and the national psoriasis foundation. he is founder and part owner of causa research and holds stock in sensal health; gh is or has been an investigator, consultant/advisor, or speaker for abbvie, athenex, boehringer ingelheim, bond avillion, bristol-myers squibb, celgene, eli lilly, novartis, janssen, leo pharma, mc2, ortho dermatologics, pellepharm, pfizer, regeneron, sanofi genzyme, sun pharma, and ucb; vc has served as an investigator, consultant, or speaker for abbvie, galderma, l’oréal, ortho dermatologics, and vyne; lhk has acted as an investigator, advisor, speaker, and consultant for ortho dermatologics; lsg has served as investigator/consultant or speaker for ortho dermatologics, leo pharma, dermavant, incyte, novartis, abbvie, pfizer, sun pharma, ucb, arcutis and lilly; nb has served as advisor, consultant, and investigator for abbvie, almirall, biofrontera, bi, brickell, bms, epi health, ferndale, galderma, incyte, isdin, j&j, laroche-posay, leo pharma, ortho dermatologics, regeneron, sanofi, sunpharma, verrica, and vyne; skt has acted as an investigator for ortho dermatologics; jaz has served as advisor, consultant, or speaker for abbvie, allergan, dermavant, dermira, epi health, galderma, incyte, johnson and johnson, l’oreal, ortho dermatologics, pfizer, procter and gamble, regeneron, sun pharma, ucb, unilever, and vyne. objectives and methods � the objective was to evaluate nnt values for combination topical acne treatments � nnt to achieve treatment success was calculated for 8 combination treatments: 7 dual-combinations (fda approved) and 1 triple-combination (in development) � treatment success was defined as ≥2-grade egss/iga improvement and clear/almost clear skin at week 12 results � treatment success rates and calculated nnt values from 13 studies are shown in the figure • eleven studies enrolled patients with moderate-to-severe acne and 2 studies included those with mild and/or very severe acne; additional inclusion/exclusion criteria are shown � the lowest nnt values (most favorable) were achieved with idp-126 gel—fixed-dose, triple combination clindamycin phosphate 1.2%, bpo 3.1%, adapalene 0.15%—which is in development for the treatment of acne idp-126 gel clin 1.2%, bpo 3.1%, adap 0.15% treatment success (%)a nnt (calculated) favors treatment severityc age, y il nil 3, 4 ≥9 30-100 35-150 3, 4 ≥12 20-100 30-150 3 2, 3, 4 ≥12 20-50 30-100 3, 4 12-70 17-40 20-100 2, 3, 4, 5 ≥12 17-40 20-150 3, 4 12-70 20-40 20-100 3, 4 ≥9 20-100 30-150 3, 4 ≥12 20-100 20-100 epiduo forte gel adap 0.3%, bpo 2.5% epiduo gel adap 0.1%, bpo 2.5% acanya gel clin 1.2%, bpo 2.5% veltin gel clin 1.2%, tret 0.025% onexton gel clin 1.2%, bpo 3.75% twyneo cream tret 0.1%, bpo 3% ziana gel clin 1.2%, tret 0.025% 20.5 50.5 24.9 49.6 11.0 33.7 11.3 30.1 5.6 21.5 14.4 28.8 10.8 28.4 17.8 33.2 14.5 28.5 14.3 39.9 15.1 26.8 7.9 22.8 8.7 21.0 vehicle active treatment 5 4 5 7 6 7 6 7 8 9 4 9 7 inclusion/exclusion criteriab adefined as percentage of patients achieving ≥2-grade reduc tion from baseline in egss/iga and clear/almost clear skin at week 12. data for approved treatments were from prescribing information and/or fda medical reviews.6 data for idp-126 were from t wo phase 3 studies.7 binclusion/exclusion criteria were for facial acne or were not specified. cstudies evaluated severit y via 5or 6 -point egss or iga. though there were slight dif ferences in definition, generally: 0=clear, 1=almost clear/minimal, 2=mild, 3=moderate, 4=severe, 5=ver y severe. 1 (% success with active treatment − % success with vehicle) * 100 microsoft word july 2020 bar 869 proof final.docx skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 361 brief articles aseptic syphilitic meningitis in an hiv-negative patient with concomitant primary and secondary syphilis antonio r. jimenez, bs1, paige hoyer, md2, michael wilkerson, md2 1the university of texas medical branch, school of medicine 2the university of texas medical branch, department of dermatology syphilis is a sexually and vertically transmitted infection caused by treponema pallidum subspecies pallidum. the spirochete penetrates the skin via intact mucous membranes or dermal microabrasions and causes disseminated infection.1 syphilis has a protean presentation and is thus known as the “great mimicker.”2 the deceptive nature of the disease can lead to under-recognition of introduction background: syphilis is a sexually and vertically transmitted disease caused by the treponema pallidum species. aseptic syphilitic meningitis (asm) is a subcategory of neurosyphilis. neurosyphilis is typically considered a tertiary manifestation of syphilis; however, asm typically occurs within six months of exposure and may be concurrent with the rash of secondary syphilis. case presentation: a 58-year-old immunocompetent male presented to the dermatology clinic with an erythematous morbilliform rash that involved his trunk and upper extremities. he was prescribed benzonatate 100 mg 3 weeks prior for cough and was diagnosed with a druginduced morbilliform rash. the patient was seen one month later by urology for a penile ulcer. at his urology appointment, a rapid plasmin reagin test was done and resulted positive with a titer of 1:256. he was referred to dermatology again and was noted to have a diffuse, coppercolored maculopapular rash involving the palms and soles. during this appointment, the patient complained of a 4-week headache and was found to have nuchal rigidity. he was admitted for neurosyphilis work up, including csf and csf-vdrl examination. his neurologic symptoms improved with iv penicillin g. repeat rpr testing at six months follow up confirmed adequate treatment and his rpr declined from 1:256 to 1:4. conclusion: we present a case of asm in an immunocompetent individual with concomitant primary and secondary syphilis. dermatologists are trained to recognize the cutaneous manifestations of syphilis, but also should be familiar with the variable presentations of the disease, including the early neurological findings of asm. abstract skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 362 serious complications or lead to a failed treatment regimen. a rare and insidious neurosyphilis sub-type called aseptic syphilitic meningitis (asm) can present in primary or secondary syphilis, with most recorded cases occurring in secondary syphilis.1,3 because neurological symptoms are not typically seen in early syphilis, asm can go unrecognized. in literature, most reported cases of asm involve hiv-positive patients; however, the disease can also afflict immunocompetent individuals.4 we present a case of an hivnegative patient who presented with the classic cutaneous manifestations of primary and secondary syphilis as well as asm. a 58-year-old immunocompetent caucasian male presented to the dermatology clinic with a diffuse, pruritic rash on his face, trunk, and upper extremities for 3-4 weeks. the patient denied pain, recent sexual contacts, or eruption of a similar rash. he had a past medical history of alcoholic cirrhosis and no pertinent family or social history. he had been prescribed benzonatate 100 mg for cough 3 weeks prior. a physical examination demonstrated erythematous papules coalescing into small plaques in a morbilliform array. it was suspected that he had a morbilliform drug eruption secondary to his benzonatate use, and he discontinued the medication. he was prescribed topical corticosteroids to treat the rash. in addition, 0.4 cm punch biopsies of his left and right chest were done. the biopsy results were non-diagnostic and there was no evidence of a drug-induced skin eruption on histology. the patient returned to the dermatology clinic one month later after he was noted to have an ulcerated plaque on his glans penis at a urology appointment. at his urology visit, a rpr, reactive syphilis igg/igm, hiv, and hsv/vzv pcr test were obtained. his hiv test was negative, hsv pcr was negative, and his rpr was positive with a titer of 1:256. his syphilis igg/igm were reactive. at his dermatology appointment, the physical examination demonstrated a copper-colored maculopapular rash that involved the palms and soles (fig 1a, 1b). a skin biopsy of his right ankle, back, and right chest were obtained. a pemphigus panel, anti-nuclear, anti-histone, anti-ssb, and anti-ssa antibody tests were ordered. the pemphigus panel was negative for igg antibodies to desmoglein-1 or -3; the antinuclear, anti-ssb, and anti-ssa antibodies were negative. a treponema pallidum particle agglutination test (tppa) was ordered and was reactive. the repeat biopsy demonstrated a lichenoid as well as superficial and deep lymphocytic infiltrate with abundant plasma cells. t. pallidum immunohistochemical staining also revealed abundant dermal spirochetes. at this visit, the patient complained of a 4week headache and was noted to have nuchal rigidity on physical examination. the patient was admitted to the hospital directly from the clinic for a neurosyphilis work-up and a lumbar puncture was done. his csf analysis demonstrated elevated protein levels but no evidence of lymphocytic pleocytosis. the csf-vdrl was negative; a meningoencephalitis panel was also negative. the patient was treated with iv penicillin g for ten days (60 doses). the patient had a drastic improvement and his headache and nuchal rigidity resolved within 48 hours of treatment initiation. while the patient’s csf results were non-diagnostic, the clinical response to penicillin and the lack of an alternative explanation led to a diagnosis of aseptic syphilitic meningitis. case presentation skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 363 over the course of six months, the patient’s rpr titer decreased from 1:256 to 1:4. figure 1. (a) secondary syphilis. the patient demonstrated a copper-colored maculopapular rash on his chest. figure 2. (b) secondary syphilis. the patient demonstrated a copper-colored maculopapular rash on his soles. syphilis presents in four consecutive clinical stages if left untreated: primary, secondary, latent, and tertiary infection. in clinical practice, one-third of patients present with concomitant symptoms and thus complicate the management of the disease.1 tertiary syphilis is often mistakenly synonymous with neurosyphilis – a classic presentation of general paresis, tabes dorsalis, and the argyll-robertson pupil. the cdc’s updated classifications on syphilis, however, have refrained from describing tertiary syphilis as a stage, but, rather, as a late clinical manifestation of the disease.5 therefore, neurosyphilis is not limited to a specific presentation or stage of syphilis. it is a broad term used to encompass a multitude of clinical syndromes.5 these syndromes include aseptic syphilitic meningitis, meningovascular syphilis, parenchymatous syphilis, and gummatous neurosyphilis.6 before the presentation of full-fledged meningitis becomes evident, there is often a subacute syphilitic prodrome that presents with non-specific neurological symptoms, including headache, vision changes, vertigo, and psychological abnormalities.1 the gold standard tests to diagnose neurosyphilis include a lumbar puncture and csf examination. a csf-vdrl or csf ftaabs can also be done to establish the diagnosis of neurosyphilis; however, a nonreactive test should not exclude the diagnosis because the sensitivity and specificity of each test is variable.3,7 asm is a subtype of meningovascular syphilis and occurs around six-months postchancre. it often presents in concurrence with the generalized rash of secondary syphilis.1 the meningeal syndrome is termed discussion skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 364 “aseptic” because there is no spirochetal cns invasion; instead, the pathogenesis of asm involves diffuse meningeal inflammation via a heightened humoral and cell-mediated immune response toward systemic spirochetes.8 asm was rare postpenicillin; however, the hiv epidemic and the co-infection of syphilis in hiv-positive patients has led to a re-emergence of the phenomenon.9 most recorded cases of asm have involved hiv-positive patients and are the result of an inadequate penicillin dose to treat a past syphilis infection. we present a patient with classic symptoms of primary and secondary syphilis, in addition to neurologic findings concerning for neurosyphilis, specifically asm. asm is less common in immunocompetent patients and may not always be considered in the differential diagnosis of patients presenting with primary or secondary syphilis. as physicians that are trained to recognize, evaluate, and treat the cutaneous manifestations of this disease, we should be well aware of asm occurring most often in the secondary stage. we should also know how to screen for asm by asking pertinent review of systems questions to ensure accurate and timely workup and treatment. conflict of interest disclosures: none funding: none corresponding author: paige hoyer, md 301 university blvd galveston, tx 77555 phone: 512-968-5742 email: pehoyer@utmb.edu references: 1. singh ae, romanowski b. syphilis: review with emphasis on clinical, epidemiologic, and some biologic features. clinical microbiology reviews. 1999;12(2):187-209. 2. peeling rw, hook ew. the pathogenesis of syphilis: the great mimicker, revisited. the journal of pathology. 2005;208(2):224-232. 3. carmo ra, moura as, christo pp, morandi ac, oliveira ms. syphilitic meningitis in hiv-patients with meningeal syndrome: report of two cases and review. brazilian journal of infectious diseases. 2001;5(5):280-287. 4. lukehart sa. invasion of the central nervous system by treponema pallidum: implications for diagnosis and treatment. annals of internal medicine. 1988;109(11):855. 5. forrestel ak, kovarik cl, katz ka. sexually acquired syphilis: historical aspects, microbiology, epidemiology, and clinical manifestations. j am acad dermatol. 2020;82(1):1-14. 6. marra cm. update on neurosyphilis. current infectious disease reports. 2009;11(2):127-134. 7. marra cm, maxwell cl, smith sl, et al. cerebrospinal fluid abnormalities in patients with syphilis: association with clinical and laboratory features. the journal of infectious diseases. 2004;189(3):369-376. 8. chahine lm, khoriaty rn, tomford wj, hussain ms. the changing face of neurosyphilis. international journal of stroke. 2011;6(2):136143. 9. wagemakers a, hepp d, killestein j, peferoen l, ang w. acute syphilitic meningitis in an hivinfected patient. idcases. 2018;13. conclusion acknowledgements: medical writing support was provided by prescott medical communications group (chicago, il) with financial support from ortho dermatologics; ortho dermatologics is a division of bausch health us, llc | presented at winter clinical dermatology conference 2020 • january 17-22, 2020 • kohala coast, hi synposis ◾ in the treatment of dermatologic disease, formulation characteristics drive efficient topical delivery and patient acceptance, with patients preferring less oily/sticky formulations (eg, foams, lotions)1 ◾ recently, a new lotion formulation that allows for simultaneous deposition of active ingredients and excipients on the skin surface was developed to be well‑liked by patients, improve adherence, and normalize epidermal barrier function2 ◾ this formulation—utilizing polymeric emulsion technology—is used to deliver lower‑dose dermatologic products • two for psoriasis: a combination halobetasol propionate 0.01%/tazarotene 0.045% (hp/taz; duobrii®) and hp 0.01% (bryhali®) • one for acne: tazarotene 0.045% (in development) ◾ upon contact with salts on the skin, the polymeric matrix (3‑d mesh) dissolves, allowing for uniform absorption of active ingredients and hydrating excipients (figure 1) objective ◾ to summarize properties of a unique vehicle lotion formulation and permeation of active drug of the hp/taz and hp lotion formulations methods ◾ skin hydration and epidermal barrier maintenance with the vehicle lotion were assessed through corneometry and transepidermal water loss (tewl; n=30) ◾ patient preference to several features of the vehicle lotion were assessed through a questionnaire (18 questions) administered to 15 participants ◾ percutaneous permeation studies were used to evaluate in vitro dermal deposition of: • hp/taz lotion vs hp 0.05% cream (ultravate) and taz 0.1% cream (tazorac) individually • hp 0.01% lotion vs 0.05% cream results polymeric emulsion technology formulation ◾ with polymeric emulsion technology, the active ingredient and moisturizing/hydrating ingredients are encapsulated within oil droplets (figure 1a) • oil droplets are uniformly dispersed within an oil‑in‑water emulsion separated by a 3‑d mesh matrix • additional water‑soluble moisturizing excipients are trapped within the 3‑d matrix ◾ once applied to the skin, the mesh instantly breaks apart, ensuring rapid, uniform, and simultaneous release of ingredients (figure 1b and c) ◾ this technology has the potential to overcome several limitations of conventional topical drug delivery, including limited skin delivery and local cutaneous irritation2 vehicle lotion: epidermal barrier function and patient preference ◾ the vehicle lotion formulation provided rapid and sustained increases in skin moisturization (figure 2) and gradual decreases in tewl (figure 3) over 24 hours ◾ most participants (93%‑100%) responded favorably (strongly agree or agree) to questions asked about attributes of the vehicle lotion (hydrating, moisturizing, skin absorption, aesthetic), such as: • skin does not feel greasy; skin feels refreshed; skin feels immediately soft and smooth; skin feels lasting hydration; skin feels more moisturized and hydrated than with what i currently use • product absorbs quickly; product absorbs quicker than what i currently use; product provides lightweight moisturization novel lotion formulation using polymeric emulsion technology for improved skin moisturization and drug permeation in patients with psoriasis emil a tanghetti, md1; linda stein gold, md2; james q del rosso, do3; stefan weiss, md4; tina lin, pharmd5; arturo angel, bs6; radhakrishnan pillai, phd6 1center for dermatology and laser surgery, sacramento, ca; 2henry ford hospital, detroit, mi; 3jdr dermatology research/thomas dermatology, las vegas, nv; 4direct dermatology, palo alto, ca; 5ortho dermatologics,* bridgewater, nj; 6bausch health us, llc,* petaluma, ca *bausch health us, llc is an affiliate of bausch health companies inc. ortho dermatologics is a division of bausch health us, llc. figure 3. skin barrier assessment using transepidermal water loss (tewl; n=30) 0 2 4 6 8 10 12 14 16 0 hours 0.25 hours 0.5 hours 1 hour 2 hours 3 hours 8 hours 24 hours m e a n s co re s ± s d vehicle lotion untreated control ***p<0.001 vs untreated control. sd, standard deviation. percutaneous absorption of hp/taz and hp ◾ higher hp permeation efficiency was seen with 0.01% lotion than 0.05% cream (figure 4) ◾ similarly, hp/taz lotion demonstrated higher cutaneous permeation efficiency of active ingredients into the dermal layers than hp 0.05% cream or taz 0.1% cream alone (figure 5) • the advantage of the hp 0.01%/taz 0.045% lotion formulation was further demonstrated when it was shown that simply layering taz 0.1% cream onto hp 0.05% cream decreased the cutaneous permeation of tazarotene2 figure 4. dermal levels following 24 hours of topical exposure to halobetasol 0.01% lotion vs halobetasol 0.05% cream (n=10) 6.17% 1.72% 0.91% 0.28% 1.97% 1.34% 0% 1% 2% 3% 4% 5% 6% 7% 8% receptor dermis epidermis p e rc e n t o f a p p lie d d o se ( m e a n ) hp 0.01% lotion halobetasol 0.05% cream hp, halobetasol propionate. figure 2. skin moisturization assessment using corneometry (n=30) 0 10 20 30 40 50 60 70 0 hours 0.25 hours 0.5 hours 1 hour 2 hours 3 hours 8 hours 24 hours m e a n s co re s ± s d vehicle lotion untreated control ***p<0.001 vs untreated control. sd, standard deviation. figure 1. novel approach to topical lotion formulation: polymeric emulsion technology a. uniform distribution c. absorption of active ingredient(s) and excipients b. mesh dissolves 3-d mesh dissolves instantly upon contact with salts on skin active ingredient(s) and moisturizing/hydrating agents uniformly absorbed by skin 1-2 μm 3-d mesh allows for uniform distribution of active ingredient(s) and moisturizing agents droplets consisting of active ingredient(s) and oil soluble moisturizing agents held apart by the 3-d mesh 25-50 μm 3-d mesh (polymeric matrix) holding water and water soluble hydrating agents within the mesh figure 5. dermal levels following 24 hours of topical exposure to halobetasol/ tazarotene lotion vs halobetasol 0.05% cream (a) or tazarotene 0.1% cream (b) 0.48% 1.37% 4.97% 0.28% 1.34% 1.72% 0% 1% 2% 3% 4% 5% 6% p e rc e n t o f a p p lie d d o se ( m e a n ) 0.004% 2.8% 18.0% 0.002% 1.5% 10.8% 0% 5% 10% 15% 20% receptor dermis epidermisreceptor dermis epidermis a. halobetasol dermal levels (n=10) b. tazarotene dermal levels (n=10) hp 0.01%/taz 0.045% lotion halobetasol 0.05% cream hp 0.01%/taz 0.09% lotion tazarotene 0.1% cream hp, halobetasol propionate; taz, tazarotene. conclusions ◾ lotion formulations for the treatment of psoriasis and acne have been developed that utilize an innovative polymeric emulsion technology and an optimal selection of solvents, emollients, and humectants ◾ the vehicle lotion formulation is non‑greasy, aesthetically pleasing, and provides enhanced barrier to the skin ◾ further, application of the lower‑dose hp/taz and hp lotion formulations resulted in higher permeation efficiency of the active ingredients compared with application of hp or taz cream alone ◾ these results suggest that this unique lotion formulation may provide a more effective, predictable, and patient‑preferred treatment option than cream formulations references 1. svendsen et al. j dermatolog treat. 2019:1‑6. 2. tanghetti et al. j dermatolog treat. 2019:1‑8. author disclosures dr. emil tanghetti has served as speaker for novartis, ortho dermatologics, sun, lilly, galderma, abbvie, and dermira; served as a consultant/clinical studies for hologic, ortho dermatologics, and galderma; and is a stockholder for accure. dr. linda stein gold has served as investigator/consultant or speaker for ortho dermatologics, leo, dermavant, incyte, novartis, abbvie, and lilly. dr. james del rosso has served as a consultant, investigator, and speaker for ortho dermatologics. dr. stefan weiss has served as consultant, speaker, advisor or research honoraria from abbvie, ortho dermatologics, jansen biotech, dermira, almirall, brickell biotech, dermtech, and scynexis. dr. tina lin is an employee of ortho dermatologics and may hold stock and/or stock options in its parent company. mr. arturo angel and dr. radhakrishnan pillai are employees of bausch heal us, llc and may hold stock and/or stock options in its parent company. copies of this e-poster obtained through qr, ar and/or text key codes are for personal use only and may not be reproduced without written permission of the authorspresented at the winter clinical dermatology conference hawaii®; january 13-18, 2023; kohala coast, hawaii https://scientificpubs.congressposter.com/p/2pbb9h4sht40u901 disclosures this study was sponsored by pfizer inc. u.b.-p. has served as a consultant and/or participated in advisory boards for abbvie, cerave, dermocosmétique vichy, galderma, lilly, neuroderm, pfizer, sanofi regeneron, and boots healthcare and is a clinical study investigator for amryt, bayer, cassiopeia, concert pharmaceuticals, pierre fabre, novartis, leo pharma, and mayne pharma. j.w.g.h. has served as a scientific advisor and/or clinical study investigator for pfizer, galderma, gsk, eucerin, johnson & johnson, janssen, sanofi, bionoox, and beiersdorf/eucerin. q.y. declares no conflicts of interests. g.j.s. is a principal clinical trial investigator for pfizer. m.k.h. declares receiving grant support from concert pharmaceuticals, eli lilly, and pfizer, and consulting fees from aslan pharmaceuticals, bioniz, cassiopeia, and pulse biosciences. g.m. declares no conflicts of interests. m.o. is a medical advisor for pfizer japan inc, taisho pharmaceutical co, eli lilly japan kk, and rohto pharmaceutical co, and receives advisory fees; he also receives lecture fees from eli lilly japan kk and research grants for projects not related to this study from maruho co, sun pharma japan ltd, and shiseido co. l.t., f.z., g.s., r.w., and u.k. are employees of pfizer and hold stock or stock options in pfizer. third-party medical writing assistance, provided by health interactions, inc, was funded by pfizer inc. references 1. islam n, et al. autoimmun rev. 2015;14:81-89. 2. king b, et al. poster presented at eadv 2021. week: 24 48 ritlecitinib 200/50 mg qd ritlecitinib 200/30 mg qd ritlecitinib 50 mg qd ritlecitinib 30 mg qd placebo → ritlecitinib 200/50 mg qd* placebo → ritlecitinib 50 mg qd* salt50 salt75 salt90 salt100 80 70 60 50 40 30 20 10 0 p ro po rt io n of p at ie nt s w ith p er ce nt ag e im pr ov em en t i n s a lt s co re , % 53% 55% 43% 45% 48% 34% 40% 36% 46% 31% 32% 22% 31% 24% 30% 22% 23% 13% 7% 11% 3% 14% 5% 10% ritlecitinib 200/50 mg qd (n=132) ritlecitinib 200/30 mg qd (n=130) ritlecitinib 50 mg qd (n=130) ritlecitinib 30 mg qd (n=132) placebo → ritlecitinib 200/50 mg qd (n=65)* placebo → ritlecitinib 50 mg qd (n=66)* salt50 (50% improvement in salt score) week 24: 42.7% 39.5% 36.4% 29.4% 7.7% 6.2% week 48: 55.2% 53.7% 47.7% 45.1% 43.4% 34.4% week 24: 18.6% 12.1% 10.7% 9.2% 1.5% 1.5% week 48: 31.0% 29.6% 23.8% 23.1% 22.1% 12.5% week 24: 31.5% 22.6% 20.7% 13.5% 3.1% 1.5% week 48: 46.4% 39.5% 36.1% 32.3% 31.2% 21.9% week 24: 7.3% 4.8% 2.5% 1.5% 1.5% 0% week 48: 14.0% 10.8% 10.4% 7.4% 4.9% 3.1% p ro po rti on o f p at ie nt s w ith s a lt 75 , % p ro po rti on o f p at ie nt s w ith s a lt 90 , % p ro po rti on o f p at ie nt s w ith s a lt 10 0, % 80 60 40 20 0 0 1284 16 20 24 salt75 (75% improvement in salt score) 28 32 36 40 44 48 80 60 40 20 0 0 1284 16 20 24 salt90 (90% improvement in salt score) 28 32 36 40 44 48 80 60 40 20 0 0 1284 16 20 24 salt100 (100% improvement in salt score) week week week 28 32 36 40 44 48 80 60 40 20 0 0 1284 16 20 24 p ro po rti on o f p at ie nt s w ith s a lt 50 , % 28 32 36 40 44 48 week ulrike blume-peytavi,1 juan walter gubelin harcha,2 qinping yang,3 george j. schmieder,4 maria k. hordinsky,5 giuseppe micali,6 manabu ohyama,7 liza takiya,8 fan zhang,9 gregor schaefer,10 robert wolk,9 urs kerkmann10 1department of dermatology, venerology and allergology, charité-universitätsmedizin berlin, germany; 2centro médico skinmed and universidad de los andes, santiago, chile; 3department of dermatology, huashan hospital, fudan university, shanghai, china; 4park avenue dermatology, orange park, fl, usa; 5department of dermatology, university of minnesota medical school, minneapolis, mn, usa; 6department of dermatology, university of catania, catania, italy; 7department of dermatology, kyorin university faculty of medicine, tokyo, japan; 8pfizer inc, collegeville, pa, usa; 9pfizer inc, groton, ct, usa; 10pfizer pharma gmbh, berlin, germany evaluation of response to ritlecitinib treatment based on salt improvement scores in patients with alopecia areata: post hoc analysis of the allegro phase 2b/3 study results • at baseline, mean salt scores ranged from 90.0 to 93.0 and were generally consistent across treatment groups (table 1) table 1. baseline characteristics ritlecitinib qd* 200/50 mg (n=132) 200/30 mg (n=130) 50 mg (n=130) 30 mg (n=132) placebo† (n=131) age mean (sd), years 35.5 (15.0) 34.4 (13.8) 32.4 (13.4) 33.7 (14.8) 34.0 (15.0) 12-17 years, n (%) 20 (15.2) 19 (14.6) 18 (13.8) 20 (15.2) 19 (14.5) ≥18 years, n (%) 112 (84.8) 111 (85.4) 112 (86.2) 112 (84.8) 112 (85.5) female, n (%) 81 (61.4) 85 (65.4) 71 (54.6) 80 (60.6) 86 (65.6) white, n (%) 92 (69.7) 90 (69.2) 79 (60.8) 91 (68.9) 94 (71.8) patients with at/au, n (%)‡ 60 (45.5) 60 (46.2) 60 (46.2) 60 (46.2) 60 (45.8) baseline salt score, mean (sd) all patients 90.3 (15.1) 90.5 (14.3) 90.3 (14.7) 90.0 (15.1) 93.0 (11.5) non-at/au‡ 82.2 (16.5) 82.4 (15.4) 82.0 (15.9) 81.5 (16.3) 87.0 (12.9) duration of current aa epsiode, mean (sd), years 3.4 (2.9) 3.4 (2.9) 3.2 (2.7) 3.6 (2.8) 3.2 (2.7) aa, alopecia areata; at, alopecia totalis; au, alopecia universalis; qd, once daily; salt, severity of alopecia tool. *ritlecitinib 10 mg was assessed for dose ranging only; data are not shown. †placebo for 24 weeks and then ritlecitinib 200/50 mg or 50 mg qd. ‡participants in the at/au category had salt scores of 100 (complete scalp hair loss) at baseline (regardless of the category in the aa history case report form). salt score improvement from baseline up to week 48 • across all ritlecitinib dose regimens tested for efficacy (200/50 mg, 200/30 mg, 50 mg, and 30 mg), a greater proportion of patients had salt 50 , salt 75 , salt 90 , or salt 100 response at week 24 vs placebo (figure 2) at week 24, 29-43% of patients in the ritlecitinib arms had a 50% improvement in salt score, with some patients reaching 100% improvement • the proportion of patients with salt score improvements continued to increase through week 48 (figures 2 and 3) at week 48, 34-55% of patients had a 50% improvement in salt score, and 3-14% of patients had a 100% improvement safety conclusions • ritlecitinib treatment led to scalp hair regrowth over 48 weeks of treatment at week 24, up to 43% of patients had a 50% improvement in salt score; a small proportion of patients had 100% improvement further improvements were seen after week 24; by week 48, up to 55% and 14% of patients showed a 50% and 100% improvement in salt score, respectively • ritlecitinib had an acceptable safety profile over 48 weeks • various salt improvement categories, including salt 50 , salt 75 , salt 90 , and salt 100 , may help facilitate discussion of treatment progress in patients with aa background • alopecia areata (aa) is an autoimmune disease that has an underlying immunoinflammatory pathogenesis and is characterized by nonscarring hair loss ranging from small bald patches to complete loss of scalp, face, and/or body hair1 • ritlecitinib, an oral jak3/tec inhibitor, demonstrated efficacy and safety in patients aged ≥12 years with aa in the allegro phase 2b/3 trial (nct03732807)2 significant improvements in the proportion of patients with severity of alopecia tool (salt) score ≤20 (≤20% scalp without hair) at week 24 (primary endpoint) were observed in active ritlecitinib treatment groups vs placebo (p<0.001)1 ritlecitinib was also found to have significantly higher salt score ≤10 (10% scalp without hair) response rates than placebo at week 24 (secondary endpoint) objective • to evaluate responses to ritlecitinib treatment based on predefined salt improvement categories from baseline to weeks 24 and 48 methods study design • the allegro phase 2b/3 trial was an international, randomized, double-blind, placebo-controlled, combined dose-ranging and pivotal study (figure 1) • patients initially received daily ritlecitinib (± a 4-week 200-mg daily loading dose): 200/50, 200/30, 50, 30, or 10 mg (10 mg assessed for dose ranging only) or placebo for 24 weeks • during the 24-week extension period, ritlecitinib groups continued on 50-, 30-, or 10-mg maintenance doses, and patients initially assigned to placebo switched to 200/50 or 50 mg daily key eligibility criteria • patients were aged ≥12 years with a diagnosis of aa and ≥50% scalp hair loss, including alopecia totalis and alopecia universalis, and a current aa episode duration of 6 months to 10 years qd, once daily; salt, severity of alopecia tool; salt 50/75/90/100 , 50%/75%/90%/100% improvement from baseline in salt score. n indicates the number of patients in each treatment group at baseline. error bars are 95% ci. *patients received placebo until week 24 and then received ritlecitinib treatment (200/50 or 50 mg qd) from week 24 to week 48. figure 3. response based on % improvement from baseline in salt scores over time qd, once daily; salt, severity of alopecia tool; salt 50/75/90/100 , 50%/75%/90%/100% improvement from baseline in salt score. percentages and error bars are 95% ci at week 48. *patients received placebo until week 24 and then received ritlecitinib treatment (200/50 or 50 mg qd) from week 24 to week 48. figure 2. response based on % improvement from baseline in salt score at weeks 24 and 48 • over 48 weeks of treatment, the most frequent adverse events (aes), with no evident dose response, were upper respiratory tract infection, nasopharyngitis, and headache • most aes were mild or moderate in severity, 12 serious aes were reported, and 26 patients permanently discontinued treatment due to aes up to week 48 • overall, there were 8 cases of herpes zoster infection, 4 serious infections, 2 malignancies (both breast cancer), and 1 pulmonary embolism; no major adverse cardiovascular events, deaths, or opportunistic infections were reported outcomes • in this post hoc analysis, the proportions of patients with 50%, 75%, 90%, and 100% improvement from baseline in salt score (salt 50 , salt 75 , salt 90 , salt 100 , respectively) were assessed at weeks 24 and 48 salt score assesses the amount of scalp hair loss with scores ranging from 0 (no scalp hair loss) to 100 (complete scalp hair loss) salt x denotes x% improvement in salt score from baseline statistical analysis • descriptive analyses were used to evaluate proportions of patients with salt 50 , salt 75 , salt 90 , and salt 100 at weeks 24 and 48 • 95% cis were calculated based on normal approximation • patients with missing data due to covid-19–related reasons at specified time points were excluded; patients with missing data due to reasons unrelated to covid-19 were considered nonresponders bl, baseline; qd, once daily; rit, ritlecitinib. figure 1. study design rit 200 mg qd rit 200 mg qd rit 50 mg qd rit 30 mg qd rit 10 mg qd placebo placebo rit 50 mg qd rit 30 mg qd rit 50 mg qd rit 30 mg qd rit 10 mg qd placebo placebo rit 50 mg qd rit 30 mg qd rit 50 mg qd rit 30 mg qd rit 10 mg qd rit 200/50 mg qd rit 50 mg qd placebo-controlled (24 weeks) study week extension (24 weeks) maintenance (20 weeks) loading (4 weeks) bl 2 4 8 12 18 26 28 34 40 4824 s cr ee ni ng r an do m iz at io n screening and randomization (35 days) n=132 n=66 n=65 n=63 n=130 n=132 n=130 open-label extension study evaluating the long-term safety, efficacy, and tolerability of fmx103 1.5% topical minocycline foam in the treatment of moderate-to-severe facial papulopustular rosacea linda stein gold, md1, james q. del rosso, do2, leon kircik, md3, neal d. bhatia, md4, deirdre hooper, md5, walter nahm, md, phd6, iain stuart, phd7 1henry ford health system, detroit, mi; 2jdr dermatology research/thomas dermatology, las vegas, nv; 3icahn school of medicine at mount sanai, new york, ny; 4therapeutics clinical research, san diego, ca; 5delricht research, new orleans, la; 6university of california, san diego school of medicine, san diego, ca; 7menlo therapeutics inc., bridgewater, nj introduction • rosacea is a chronic, inflammatory disorder involving the face that is characterized by central facial erythema, flushing, telangiectasia, edema, papules, and pustules1-3 • oral tetracyclines, such as doxycycline and minocycline, are among the common therapies that are used for treating the disorder with oral, sub-microbial doxycycline currently approved for this indication. however, these agents have been associated with antibiotic resistance, adverse side effects, such as gastrointestinal upset and permanent hyperpigmentation, and following treatment cessation, the tendency for disease relapse is high3-7 • the efficacy and safety of fmx103 1.5% topical minocycline foam in treating moderate-to-severe rosacea have previously been reported in two, 12-week, double-blind, vehicle-controlled, phase 3 studies (study 11 and study 12)8 • objective: to demonstrate the long-term safety, tolerability and efficacy of topical fmx103 1.5% minocycline foam in moderate to severe facial papulopustular rosacea for up to 52 weeks. methods • fx2016-13 (study 13) was an open-label, multicenter, 40-week extension study to evaluate the long-term safety, tolerability, and efficacy of fmx103 1.5% topical foam in the treatment of moderate-to-severe facial papulopustular rosacea (figure 1) • subjects were eligible to enter study 13 upon successful completion of either double-blind study (study 11 or study 12) – there was no limit on the number of subjects who could enter the open-label phase • concomitant use of prescription or otc medications that the subjects were taking or any change in dosage was permitted and recorded • investigator global assessments (igas) were based upon a 5-point scale with 0=clear, 1=almost clear, 2=mild, 3=moderate, and 4=severe figure 1. study design week 52baseline key inclusion criteria for db study • males and nonpregnant females ≥18 years • moderate-to-severe facial papulopustular rosacea (iga score of 3 or 4) • >15 to ≤75 facial papules and pustules, excluding lesions involving eyes and scalp; ≤2 nodules on the face • presence or history of facial erythema or flushing co-primary efficacy endpoints • absolute change in the inflammatory lesion count at week 52 compared to db baseline • iga success rate (dichotomized as yes/no) at week 52, where success was defined as an iga score of 0 or 1, and at least a 2-grade improvement (decrease) from db baseline secondary efficacy endpoints • the absolute and percent change from db baseline in inflammatory lesion count at weeks 16, 22, 28, 34, 40, 46, and 52 of the ol study • the dichotomized iga success rate at weeks 16, 22, 28, 34, 40, and 46 • the subject satisfaction questionnaire (ssq) at week 52 week 12 fmx103 1.5% (505 enrolled, 504 in safety population, 410 completed) double-blind, vehicle-controlled (n=1522) open-label (fx2016-13) for subjects who completed the db study visit every 6 weeks vehicle foam (n=256) fmx103 1.5% (n=495) vehicle foam (n=257) fmx103 1.5% (n=514) s tu dy 1 1 s tu dy 1 2 iga, investigator’s global assessment; db, double-blind study; ol, open-label study; otc, over-the-counter. results subject disposition and double-blind baseline demographics • as shown in figure 2, 504 subjects who completed the db study (study 11: n=217; study 12: n=287) comprised the all treated (safety) population in the ol extension study (study 13) figure 2. subject disposition 3 discontinuation adverse event = 5 abnormal laboratory follow-up = 0 lost to follow-up = 29 subject request = 50 protocol deviation = 0 other = 9completed ol study (n=410) fmx103/fmx103, n=276 (83%) vehicle/fmx103, n=134 (78%) study 11 randomized (n=751) completed db study (fmx103 1.5%) n=437 completed db study (vehicle) n=232 entered ol study n=140 (32%) entered ol study n=77 (24%) study 12 randomized (n=771) completed db study (fmx103 1.5%) n=479 completed db study (vehicle) n=239 entered ol study n=192 (40%) entered ol study n=95 (40%) study 13 total entering ol study (n=505*) total in safety population (n=504) fmx103/fmx103, n=332 (36%) vehicle/fmx103, n=172 (37%) *one subject who was enrolled discontinued the same day prior to taking the study drug and was therefore excluded from the safety population. • double-blind demographics, double-blind baseline characteristics, and concomitant use of medication during the ole study are shown in table 1 table 1. double-blind baseline demographics, disease characteristics, and concomitant use of medication variable fmx103/ fmx103 (n=332) vehicle foam/ fmx103 (n=172) overall (n=504) mean age (sd) 18 to 40 years 41 to 64 years ≥ 65 years 51.1 (12.62) 68 (20.5) 214 (64.5) 50 (15.1) 51.9 (11.90) 26 (15.1) 121 (70.3) 25 (14.5) 51.4 (12.37) 94 (18.7) 335 (66.5) 75 (14.9) gender, n (%) male female 91 (27.4) 241 (72.6) 62 (36.0) 110 (64.0) 153 (30.4) 351 (69.6) race, n (%) white black other 321 (96.7) 5 (1.5) 6 (1.8) 163 (95.3) 3 (1.8) 6 (1.8) 484 (96.2) 8 (1.6) 12 (2.4) mean inflammatory lesion count, n (sd) 28.8 (12.63) 28.7 (11.93) 28.8 (12.38) iga score, n (%) 3 – moderate 4 – severe 301 (90.7) 31 (9.3) 149 (86.6) 23 (13.4) 450 (89.3) 54 (10.7) any concomitant medication during the study, n (%) vitamins lipid modifying agents agents acting on the renin-angiotensin system antibiotics and chemotherapeutics for dermatological use antifungals for dermatological use other dermatological preparations 273 (82.2) 81 (24.4) 76 (22.9) 72 (21.7) 6 (1.8) 6 (1.8) 9 (2.7) 137 (79.7) 39 (22.7) 38 (22.1) 35 (20.3) 4 (2.3) 1 (0.6) 3 (1.7) 410 (81.3) 120 (23.8) 114 (22.6) 107 (21.2) 10 (2.0) 7 (1.4) 12 (2.4) baseline is defined as the baseline visit in the double-blind study; iga, investigator’s global assessment; sd, standard deviation. safety and tolerability • summary of all adverse events in the all treated population is shown in table 2 • the majority of the treatment-emergent adverse events (teaes) were considered mild or moderate in severity and no serious teaes were related to treatment table 2. summary of teaes, rates of discontinuation and overall fmx103 1.5% treatment duration in the ol extension variable fmx103 1.5%/ fmx103 1.5% (n=332) vehicle foam/ fmx103 1.5% (n=172) overall (n=504) subjects with any ae, n (%) 151 (45.5) 70 (40.7) 221 (43.8) subjects with any teae, n (%) 137 (41.3) 64 (37.2) 201 (39.9) subjects with any serious teae, n (%) 9 (2.7)a 4 (2.3)b 13 (2.6) subjects with treatment-related teaes, n (%) 5 (1.5)c 8 (4.7)d 13 (2.6) subjects with serious treatment-related teaes, n (%) 0 (0.0) 0 (0.0) 0 (0.0) subjects discontinued due to ae, n (%) 3 (0.9)e 2 (1.2)f 5 (1.0) teaes resulting in death, n (%) 0 (0.0) 0 (0.0) 0 (0.0) subjects exposed to > 6 months (>168 days), n (%) 319 (96.1) 146 (84.9) 465 (92.3) subjects exposed to > 1 year (>350 days), n (%) 272 (81.9) 0 (0.0) 272 (54.0) number (%) of subjects with at least 1 ae per category; ae, adverse event; teae, treatment-emergent adverse event alabyrinthitis, periorbital cellulitis, pneumonia, staphylococcal infection, cerebrospinal fluid leakage, cerebrovascular accident, syncope, subdural hematoma, death, hypokalemia, malignant melanoma bappendicitis perforated, post procedural hemorrhage, large intestinal instruction, chronic obstructive pulmonary disease cmydriasis, angular cheilitis, herpes simplex, dermatitis contact, hair color changes ddiarrhea, conjunctivitis, sunburn, acne, dermatitis contact, erythema, pruritus, rosacea, skin lesion edermatitis contact, mydriasis, enchondromatosis frosacea, anemia, leukocytosis, appendicitis perforated, sepsis, appendicectomy • teaes occurring in at least 2% of open-label subjects from either arm of the double-blind phase are shown in table 3 table 3. teaes in the ol extension variable fmx103 1.5%/ fmx103 1.5% (n=332) vehicle foam/ fmx103 1.5% (n=172) overall (n=504) subjects with one or more teae, n (%) 137 (41.3) 64 (37.2) 201 (39.9) infections and infestations upper respiratory tract infection viral upper respiratory tract infection sinusitis influenza bronchitis urinary tract infection 14 (4.2) 14 (4.2) 8 (2.4) 9 (2.7) 8 (2.4) 8 (2.4) 5 (2.9) 5 (2.9) 9 (5.2) 5 (2.9) 2 (1.2) 1 (0.6) 19 (3.8) 19 (3.8) 17 (3.4) 14 (2.8) 10 (2.0) 9 (1.8) nervous system disorders headache 8 (2.4) 2 (1.2) 10 (2.0) vascular disorders hypertension 7 (2.1) 1 (0.6) 8 (1.6) teae, treatment-emergent adverse event • local facial assessments at week 52 demonstrated that fmx103 1.5% topical minocycline foam was well tolerated during the ol extension study (figure 3) figure 3. facial tolerability assessed at week 52 0 14.2 3.8 0.2 45.1 29.0 29.4 66.3 10.7 0% 25% 50% 75% 100% bl wk 52 erythema 1.5 0.5 1.0 0.70.5 0.4 chart title0=none 1=mild 2=moderate 3=severe 6.0 19.0 64.7 97.0 17.1 57.6 45.2 80.3 53.6 86.3 62.1 90.0 62.1 79.1 57.5 66.3 23.4 3.0 42.3 36.9 38.3 18.2 35.3 13.2 30.6 9.0 30.6 20.2 36.5 14.7 11.9 36.9 5.0 16.5 10.7 7.3 7.3 3.8 0% 25% 50% 75% 100% bl wk 52 bl wk 52 bl wk 52 bl wk 52 bl wk 52 bl wk 52 bl wk 52 % o f p op ul at io n hyperpigmentation peeling/ desquamation itchingdryness/ xerosis flushing/ blushing burning/ stinging telangiectasia clear severe moderate mild almost clear 0.8 0.5 note: percentages exclude missing responses as 60 responses were missing from the fmx103/fmx103 group (n=272) and 43 responses were missing from the vehicle/fmx103 group (n=129). bl refers to baseline of the double-blind study hyperpigmentation was evaluated as post-inflammatory hyperpigmentation long-term efficacy • treatment with fmx103 1.5% during the 40-week ol extension study was associated with reduction in inflammatory lesions relative to the db and ol baselines, regardless of previous treatment during the db studies (figure 4) figure 4. absolute (a) and percent (b) change from db baseline in inflammatory lesions -100 -75 -50 -25 0 0 4 8 12 16 22 28 34 40 46 52 % r ed uc tio n fr om d b b as el in e in in fla m m at or y le si on c ou nt -25 -20 -15 -10 -5 0 0 4 8 12 16 22 28 34 40 46 52 m ea n re du ct io n fr om d b b as el in e in in fla m m at or y le si on c ou nt db study vehicle group switched to active treatment fmx103 1.5%/fmx103 1.5% (n=332) ba -46.4% 62.4% 80.9% 83.0% vehicle/fmx103 1.5% (n=172) db study vehicle group switched to active treatment fmx103 1.5%/fmx103 1.5% (n=332) -12.8 17.9 vehicle/fmx103 1.5% (n=172) -22.5 -23.0 week week db, double-blind study; change from baseline is calculated as the value at baseline minus the post-baseline value • at the end of the study, 81.6% of the fmx103/fmx103 patients, and 76.0% of the vehicle/fmx103 patients, achieved iga treatment success (figure 5) figure 5. iga treatment success 0 19 37.8 47.6 50.6 60.1 68.1 69.1 72.4 73.5 81.6 0.0 12.2 32.6 39.0 48.2 54.5 64.0 64.4 65.9 72.1 76.0 0 25 50 75 100 0 4 8 12 16 22 28 34 40 46 52 % o f p op ul at io n w ith ig a t re at m en t s uc ce ss week fmx103/fmx103 vehicle/fmx103 number of subjects remaining in the study week 0 4 8 12 16 22 28 34 40 46 52 fmx103/ fmx103 332 332 331 332 326 321 310 298 286 279 272 vehicle/ fmx103 172 172 172 172 168 156 150 146 138 136 129 db study * db, double-blind study; iga, investigator’s global assessment *week 12 of the db study serves as the baseline for the ole study subject satisfaction • at the end of the open-label study there was a high rate of subject satisfaction with fmx103 1.5% for the treatment of papulopustular rosacea (figure 6) figure 6. subject satisfaction questionnaire results at week 52 all treated population, n=504 compared to other products 55%28% 11% 5% 1% 59%24% 11% 5% 1% overall satisfaction with product 59%24% 9% 7% 1% recommend to friend very satisfied very dissatisfieddissatisfied somewhat satisfiedsatisfied very likely very unlikelyunlikely somewhat likelylikely percentages exclude 110 missing responses summary limitations • because of the nature of the open-label study, no inference can be made on comparability due to the absence of a vehicle-treated control conclusions • fmx103 1.5% appeared to be safe and well tolerated for the long-term treatment of papulopustular rosacea for up to 52 weeks of treatment • no minocycline-induced hyperpigmentation was observed • throughout 52 weeks of treatment, fmx103 1.5% continued to be associated with a decreasing number of inflammatory lesions, as well as with improvement in overall disease severity, as assessed by iga scores • patient satisfaction levels were high, with >80% of all subjects being either satisfied or very satisfied with fmx103 1.5% disclosures/acknowledgment disclosures dr. stein gold is an advisor and investigator for foamix, galderma, leo pharma, novartis, and valeant and is an investigator for janssen, abbvie, and solgel and an advisor and investigator for novartis. dr. del rosso is a consultant for aclaris, almirall, athenex, cutanea, dermira, ferndale, galderma, genentech, leo pharma, menlo, novan, ortho, pfizer, promius, sanofi/regeneron, skinfix, and sunpharma; he has received research support from aclaris, almirall, athenex, botanix, celgene, cutanea, dermira, galderma, genentech, leo pharma, menlo, novan, ortho, promius, regeneron, sunpharma, and thync; he receives honoraria from aclaris, celgene, galderma, genentech, leo pharma, novartis, ortho, pfizer, promius, sanofi/regeneron, and sunpharma; and he participates in speakers bureaus for honoraria from aclaris, celgene, galderma, genentech, leo pharma, novartis, ortho, pfizer, promius, sanofi/regeneron, and sunpharma. dr. bhatia is an investigator and consultant for foamix pharmaceuticals. dr. hooper served as an investigator for foamix pharmaceuticals; she reports personal fees from delricht research during the conduct of the study; honoraria from allergan, almirall aesthetics, aqua galderma usa, cutera, inc., ferndale, la roche posay, pixacore, rbc consultants (clarisonic), revance, and viviscal; and other financial benefits from actavis, dermira, gsk, mylan, and sol gel. dr. nahm is an investigator for foamix pharmaceuticals. dr. iain stuart is an employee and stockholder at menlo therapeutics inc. this study is funded by foamix pharmaceuticals ltd, a wholly owned subsidiary of menlo therapeutics inc. acknowledgment editorial support was provided by scient healthcare communications. references 1. li wq, cho e, khalili h, et al. rosacea, use of tetracycline, and risk of incident inflammatory bowel disease in women. clin gastroenterol hepatol. 2016;14(2):220-225. 2. taieb a, stein gold l, feldman sr, et al. cost-effectiveness of ivermectin 1% cream in adults with papulopustular rosacea in the united states. j manag care spec pharm. 2016;22(6):654-665. 3. rainer bm, kang s, chien al. rosacea: epidemiology, pathogenesis, and treatment. dermatoendocrinol. 2017;9(1):e131574. 4. goldgar c, keahey dj, houchins j. treatment options for acne rosacea. am fam physician. 2009;80(5):461-468. 5. oge lk, munchie hl, phillips-savoy ar. rosacea: diagnosis and treatment. am fam physician. 2015;92(3):187-196. 6. fiscus v, hankinson a, alweis r. minocycline-induced hyperpigmentation. j community hosp. 2014;4:24063. 7. valentín s, morales a, sánchez jl, rivera a. safety and efficacy of doxycycline in the treatment of rosacea. clin cosmet investig dermatol. 2009;2:129-140. 8. stein gold l, del rosso jq, kircik l, et al. minocycline 1.5% foam for the topical treatment of moderate-to-severe papulopustular rosacea: results of two phase 3, randomized, clinical trials. j am acad dermatol. in press. microsoft word july 2020 edt rigel 937 proof final.docx skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 304 editorials gene expression profile testing in skin cancer prognosis: the data is clear – it’s time to get on board darrell s. rigel, md, ms1, roger i. ceilley, md2, graham h. litchman, do, ms3, clay j. cockerell, md4 1clinical professor of dermatology, nyu grossman school of medicine, new york, ny 2clinical professor of dermatology, the university of iowa school of medicine, iowa city, ia 3dermatology resident, st. john’s episcopal hospital, new york, ny 4clinical professor of dermatology and pathology, university of texas southwestern medical center, dallas, tx prognosis in skin cancer has traditionally been based on subjective clinical and histologic parameter-based systems, the most prominent of them being american joint committee on cancer (ajcc) staging. “early” melanomas have good outcomes and “advanced” cases have significant mortality and morbidity. however, clinical and pathological concordance and reproducibility remain low, suggesting that these subjective prognostic indicators fall below the limits of reliability in these staging schemata.1 for that reason, there have been calls to augment these traditional approaches using objective molecular and genetic techniques to improve the accuracy for the staging of skin cancer patients.2 a large number of independent, peer-reviewed studies evaluating gene expression profile tests have been published (see table), yet transition of these molecular-based tests into clinical care has not been as rapid for cutaneous melanoma as might have been expected, based on the data. here, we explore some of the non-scientific and political reasons why this may be the case. gene expression profile (gep) prognostic testing was originally developed for uveal melanomas where its use has become standard-of-care. there are several versions of the test under development but the currently approved, most widely used and broadly validated cutaneous version of the test stratifies risk of metastasis through the assessment of the degree of expression of 31 genes related to melanoma progression. its utility has been widely recognized by clinicians. over 16,000 melanomas in the us were 31-gep assessed in 2019. validity and utility of the 31-gep test has been proven in a number of ways. the test has been directly validated for 5-year recurrence risk in retrospective and prospective studies including over 1,500 patients. those studies demonstrated that the test accurately predicts metastasis risk independent of clinical and pathologic factors, with strong sensitivity and negative predictive value (npv). additionally, a significantly poorer prognosis has been observed for identified high-risk patients across all studies to date. multivariate regression analysis has consistently shown independent and generally superior prognostic accuracy of the 31-gep test compared to sentinel lymph node biopsy skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 305 (slnbx) and other clinicopathologic factors (table). 31-gep accuracy has also been positively reported in 2 recent systematic reviews/meta-analyses as meeting the highest standards for prognostic tools as described by the strength of recognition taxonomy (sort) system.3,4 the test has consistently improved upon the critical accuracy metrics of sensitivity and npv over those assessed by clinicopathologic staging alone, including patients who were diagnosed with thin tumors, in published validation studies that have included nearly 2,700 patients. given that some ajcc criteria are somewhat subjective and some (such as breslow thickness) may be underestimated from sampling error,5 this may explain how the addition of the objective 31-gep information to the ajcc system has been demonstrated to statistically significantly improve prognostic assessment beyond ajcc alone.6 the 31gep test has also been shown to assess the probability of sln positivity in t1-t2 lesions.7 in addition, studies have demonstrated that the integration of 31-gep data into management evaluation influences management intensity appropriately.8 more importantly, because there are so many more slnbxthan + patients and thin than thicker lesions, the absolute number of people who die in these aggregate “low-risk” groups are greater than in the high-risk groups identified through ajcc criteria alone.9 studies have demonstrated that the 31-gep test identifies high-risk melanoma patient subsets that are more likely to experience metastasis/death within low-risk patient groups who have slnbxdisease, stage i to iia tumors, and thin tumors.10 these findings have led to modification of the national comprehensive cancer network (nccn) guidelines to recommend that gep for melanoma can provide useful information on individual risk of recurrence as an adjunct to standard ajcc staging11 and been validated by the standards required for cms for insurance coverage of the test in the medicare population for evaluation of candidates for slnbx. despite this overwhelming evidence, some have still raised objections to integrating this approach into melanoma management.12 critics suggest that this test has not been fda approved and therefore its validity has been questioned. however, as this test is not a drug or device, fda approval is not required but the appropriate federal approval for this type of test (clia) was obtained. their suggestion that all identified higherrisk thin melanoma patients will automatically have more intense follow-up regimens is also not supported by impact studies. rather, these studies demonstrated that, like any clinical data, the additional information provided by 31-gep testing was not blindly followed but was appropriately integrated as part of the overall management decision process.8 they derive “consensus” statements using only a 50% agreement threshold when this process typically requires a supermajority. they support a prognostic test (slnbx) with significant morbidity but criticize the 31-gep test which has been shown in some studies to be prognostically superior with no morbidity. they ignore multiple prospective trials that have demonstrated efficacy and wrongly suggest that prospective randomized controlled trials are needed for validation when these are not required (or even possible to perform for prognostic tests as there is no way to interpret a control [nontested] group) for purely evaluating prognostic tests.13 skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 306 table. representative clinical validity, utility and impact studies for the 31-gep test for melanoma prognosis abbreviations: at – adjuvant therapy; bt – breslow thickness; cmro – current medical research and opinion; cu – clinical utility; cv – clinical validity; fu – followup; hr – hazard ratio; i – imaging; jaad – journal of the american academy of dermatology; jeavd – journal of the european academy of dermatology and venereology; l – laboratory workup; mr – mitotic rate; or – odds ratio; r – referral; slnb – sentinel lymph node biopsy; u – ulceration; * p≤0.01; **p≤0.0001; ¥multivariate analysis was not performed in this study clinical validity studies study design; objective n multivariate comparators gep risk (recurrence) greenhaw, j am acad dermatol 2020 sr/ma 1,479 bt, u, slnb, age class 2b hr=2.9** litchman, skin j cut medicine, 2020 sr/ma 1,407 bt, u, slnb class 2b hr=7.2** gastman, head neck 2019 archival; cv 157 bt, u, slnb, mr class 2 hr=3.0 gastman, j am acad dermatol 2019 archival; cv 690 bt, u, slnb, mr class 2b hr=2.92** keller, cancer med 2019 prospective; cv 159 bt, u, slnb, age class 2 hr=9.2** podlipnik, j eur acad dermatol venearol 2019 prospective; cv 86 ajcc, age class 2 hr=18.8* vetto, future oncol 2019 retrospective; cv, cu 1,421 n/a n/a greenhaw, dermatol surg 2018 prospective; cv 256 n/a class 2 or=22¥ zager, bmc cancer 2018 retrospective; cv 523 bt, u, slnb, mr class 2 hr=5.40** hsueh, j hematol oncol 2017 prospective; cv, cu 322 bt, u, slnb, mr class 2 hr=7.15* clinical utility studies study design; objective n modified surveillance management change rates dillon, skin: j cutan med 2018 prospective; cu 247 fu, i, l 49% schuitevoerder, jdd 2018 retrospective, cu 91 fu, r, at 52% berger, curr med res opin 2015 retrospective; cu 156 fu, i, l, r 53% clinical impact studies study design n target groups risk-appropriate management impact mirsky, j drugs in dermatol 2018 patient vignette; adjunctive testing 164 dermatology nps/pas yes svoboda, j drugs in dermatol 2018 patient vignette; gep recommendations 181 dermatologists yes farberg, j drugs in dermatol 2017 patient vignette; bt inflection points; adjunctive testing 169 dermatology residents yes skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 307 consensus-based appropriate usage criteria for 31-gep testing have been developed and published.14 equally important to recognize is that 31-gep testing is not for use in all lesions. usage has not been validated with in-situ and stage iv melanomas nor for predicting patient response to therapies. in addition, melanomas with breslow thickness <0.3mm may not benefit.15 finally, the usage of gep testing for skin cancer prognosis has now extended beyond melanoma. a 40-gep test has shown early promise for assessing prognosis in patients with advanced cutaneous squamous cell carcinoma.16 there have now been over 20 independent peer-reviewed data-driven studies demonstrating consistent clinical validity, efficacy, and positive impact of the 31-gep test. given this strong existing supportive published evidence, discounting the value of gep testing based on hypothetical models, inter-specialty competition with concerns regarding personal adverse economics or personal biases/conflicts for those that may be developing competitive methodologies leading to the subjective/hypothetical defining of “harm” for patients is not data justified. an objective review of published data clearly demonstrates that we have now reached the point where, given the evidence, gep testing for melanoma prognosis is long beyond the suggestion that it is just for “experimental” usage. it’s time for this debate to be concluded so that our patients can benefit. the train has left the station. it’s time to get on board. conflict of interest disclosures: dr. rigel has served on an advisory board, has been an investigator, and has received honoraria from castle biosciences. dr. ceilley has served on an advisory board for castle biosciences. dr. litchman has no relevant disclosures or conflicts of interest. dr. cockerell has served as a consultant for castle biosciences. funding: none corresponding author: darrell s. rigel, md, ms 35 e 35th st. #208 new york, ny 10016 phone: 212-684-4542 email: darrell.rigel@gmail.com references: 1. elmore jg, elder de, barnhill rl, et al. concordance and reproducibility of melanoma staging according to the 7th vs 8th edition of the ajcc cancer staging manual. jama netw open. 2018;1(1):e180083. doi:10.1001/jamanetworkopen.2018.0083 2. ferguson pm, gershenwald je, scolyer ra. staging of cutaneous melanoma: is there room for further improvement? jama netw open. 2018;1(1):e180086. doi:10.1001/jamanetworkopen.2018.0086 3. greenhaw bn, covington kr, kurley sj, yeniay y, cao na, plasseraud km, cook rw, hsueh ec, gastman br, wei ml, molecular risk prediction in cutaneous melanoma: a metaanalysis of the 31-gene expression profile prognostic test in 1,479 patients, journal of the american academy of dermatology (2020), doi.org/10.1016/j.jaad.2020.03.053. 4. litchman g, prado g, teplitz r, rigel ds. a systematic review and meta-analysis of gene expression profiling for primary cutaneous melanoma prognosis. skin j cutan med, 2020 may vol 4(3):221-237. doi: 10.25251/skin.4.3.3 5. bax mj, johnson tm, harms pw, schwartz jl, zhao l, fullen dr, chan mp. detection of occult invasion in melanoma in situ. jama dermatol. 2016 nov 1;152(11):1201-1208. doi: 10.1001/jamadermatol.2016.2668. 6. ferris lk, farberg as, middlebrook b, johnson ce, lassen n, oelschlager km, maetzold dj, cook rw, rigel ds, gerami p. identification of high-risk cutaneous melanoma tumors is improved when combining the online american skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 308 joint committee on cancer individualized melanoma patient outcome prediction tool with a 31-gene expression profile-based classification. j am acad dermatol. 2017 may;76(5):818825.e3. doi: 10.1016/j.jaad.2016.11.051. 7. vetto jt, hsueh ec, gastman br, dillon ld, monzon fa, cook rw, keller j, huang x, fleming a, hewgley p, gerami p, leachman s, wayne jd, berger ac, fleming md. guidance of sentinel lymph node biopsy decisions in patients with t1-t2 melanoma using gene expression profiling. future oncol. 2019 apr;15(11):12071217. doi:10.2217/fon-2018-0912. 8. farberg as, glazer am, white r, rigel ds. impact of a 31-gene expression profiling test for cutaneous melanoma on dermatologists' clinical management decisions. j drugs dermatol. 2017;16(5):428-431. 9. landow sm, gjelsvik a, weinstock ma. mortality burden and prognosis of thin melanomas overall and by subcategory of thickness, seer registry data, 1992-2013. j am acad dermatol. 2017 feb;76(2):258-263. doi: 10.1016/j.jaad.2016.10.018. epub 2016 nov 22. 10. gastman b, gerami p, kurley s, cook r, leachman s, vetto j. identification of patients at risk of metastasis using a prognostic 31-gene expression profile in subpopulations of melanoma patients with favorable outcomes by standard criteria. j am acad dermatol 2019;80:149-57. 11. swetter sm, et. al. nccn clinical practice guidelines in oncology: cutaneous melanoma. april 9, 2020. national comprehensive cancer network; 2020. 12. kovarik c, chu e, adamson a. gene expression profile testing for thin melanoma; evidence to support clinical use remains thin. jama dermatol 2020 online publication. 13. mathes t, pieper d. an algorithm for the classification of study designs to assess diagnostic, prognostic and predictive test accuracy in systematic reviews. systematic reviews. 2019 sep;8(1):226. doi: 10.1186/s13643-019-1131-4. 14. berman, b., ceilley, r., cockerell, c., ferris, l., high, w., lebwohl, m., nestor, m., rosen, t., litchman, g., prado, g., svoboda, r., & rigel, d. (2019). appropriate use criteria for the integration of diagnostic and prognostic gene expression profile assays into the management of cutaneous malignant melanoma: an expert panel consensus-based modified delphi process assessment. skin the journal of cutaneous medicine, 2019;3(5), 291-306. doi:https://doi.org/10.25251/skin.3.5.1 15. marks, e., caruso, h., kurley, s., ibad, s., plasseraud, k., monzon, f., & cockerell, c. (2019). establishing an evidence-based decision point for clinical use of the 31-gene expression profile test in cutaneous melanoma. skin the journal of cutaneous medicine, 2019;3(4), 239249. doi:https://doi.org/10.25251/skin.3.4.2 16. wysong a, newman jg, covington kr, kurley sj, ibrahim sf, farberg as, bar a, cleaver nj, somani ak, panther d, brodland dg, zitelli j, toyohara j, maher ia, xia y, bibee k, griego r, rigel ds, plasseraud km, estrada s, sholl lm, johnson c, cook rw, schmults cd, arron st. validation of a 40-gene expression profile test to predict metastatic risk in localized high-risk cutaneous squamous cell carcinoma. j am acad dermatol. 2020 apr 25. pii: s01909622(20)30704-0. doi:10.1016/j.jaad.2020.04.088. study of adult atopic dermatitis and comorbidities in the us department of defense (dod) healthcare system jonathan i. silverberg, md, phd, mph1, lisa beck, md2, mark boguniewicz, md3, thuy lin, cdr usn, mc,4 amber m. evans, mph,5 dharm s. patel, phd6, toni rush, mph,5 andrine r. swensen, ms, phd6 1george washington school of medicine and health sciences, washington, dc; 2departments of dermatology, medicine and pathology, university of rochester medical center, rochester, ny; 3national jewish health and university of colorado school of medicine; 4nmcp, portsmouth, va; 5health researchtx, llc, trevose, pa; 6leo pharma inc., madison, nj introduction  atopic dermatitis (ad) is a heterogeneous, chronic inflammatory disease1  the 1-year us prevalence of adult ad was 7.2%-10.2% in 201020121  the relationship between ad and allergic diseases is well established, but less is known about the prevalence and association between ad and non-allergic conditions  current studies are survey-based and have limitations due to recall, misclassification bias and lack of verification against clinical records2  this study aims to further inform the literature on the diagnosis, treatment and comorbid disease burden of ad within a diverse population poster presented at the 17th annual winter clinical dermatology conference hawaii® puako, hi, january 17-22nd, 2020 the objective of this study is to characterize and compare the prevalence of comorbidities by ad status (ad and non-ad) within an adult dod, non-veterans affairs, population objective  based on the high retention rate, minimal data lag, comprehensive capture of healthcare events, as well as evidence of research quality data as reflected in publications, the dod is well suited to successfully accomplish the objective of this study3  the findings, which represent clinically confirmed comorbidities, highlight the presence of type 2 immunity mediated diseases in the initial ad cohort  these preliminary results further define the complexity of ad and its associated comorbidities, which may inform decisions regarding treatment pathways  this retrospective cohort study demonstrates a novel use of the dod for atopic dermatitis research  additional analyses are planned to further define ad patient characteristics and disease burden, understand the prevalence of comorbidities in non-ad matched patients, and document treatment patterns in the us dod conclusions references 1. https://www.ncbi.nlm.nih.gov/pubmed/28577797 2. brusco nk, watts jj. empirical evidence of recall bias for primary health care visits. bmc health serv res. 2015;15:381. 3. dorrance cdr ka, ramchandani lcdr s, neil n, fisher h. (2013) leveraging the military health system as a laboratory for health care reform. military medicine, 178, 2:142 methods  the dod healthcare system will be the centralized data source used to identify a retrospective cohort to conduct the study  identify adult ad and non-ad patients utilizing matching (1:1) on age, gender, region, and index date (month/year) between january 1, 2016 through december 31, 2018  inclusion criteria: ≥2 ad diagnosis codes by a dermatologist, allergist or primary care provider as well as a 3-year baseline ad disease free period  exclusion criteria: active duty personnel and patients missing age and sex data  comorbidities will be identified by ≥1 icd-9/10 diagnosis code(s) during the baseline and follow-up periods and dichotomized as y/n  demographics and clinical characteristics will be documented using descriptive statistics for categorical variables for both the ad and non-ad cohorts  conditional logistic regression modeling will be utilized to determine the association between ad status and follow-up period comorbidities  subgroup and sensitivity analyses are planned to assess impact, if any, on the final results preliminary results  14,447 initial adult ad patients were identified between 2016-2018 and are available for matching to non-ad patients  64% of the identified adult ad patients were female  the mean age is 56.3 years old (sd 20)  the median age is 59 years old (iqr: 41-72) figure 1. major dod medical facilities data source selection rationale  one of the largest employers and healthcare plans in the world with patients in all 50 states and multiple countries globally  eligible beneficiaries include active duty personnel, retirees and dependents which make-up a large pediatric and elderly population  the dod is separate from the veterans administration (va) health system  an integrated inpatient, outpatient and er healthcare system capturing both the dod facility and the civilian/private sector care for eligible beneficiaries  95% of ambulatory care visits are documented  60% of dod care in the private sector is captured  beneficiaries are demographically similar to the us population in terms of age, sex and acute/chronic diseases  manages a robust formulary with minimal ordering restrictions  orders are 100% computerized provider order entry  20 years of eprescribing  captures full cost data and medicare-eligible patient data  accredited by the joint commission and follows the same standards of care expected of civilian institutions  results are populated directly from lab, pharmacy and radiology systems  mortality data is captured and considered to be more current than national death index or social security death index  the electronic health record (ehr) is equivalent to the patient chart making accuracy very high  quality checks are utilized throughout the system to ensure data integrity  dod is capturing:  ~10 million active patients (millions more covered lives)  over 1.5m patient encounters per week  over 2.5m prescriptions per week  over 2,000 births per week  20,000+ uniformed physicians/400,000+ network providers  60+ global military treatment facilities (hospitals) and 400+ clinics supported by 132,000 dod healthcare professionals  each beneficiary has a longitudinal health record figure 2. preliminary ad cohort by age group 19% 41% 40% 0% 5% 10% 15% 20% 25% 30% 35% 40% 45% 18-34 35-64 ≥ 65 age group (years) figure 3. comorbidities of interest during the 1-year baseline period prior to index in ad patients in the dod database 2.4% 2.4% 0.6% 11.7% 1.0% 11.3% 7.2% 17.0% 12.3% 0.5% 22.7% 2.1% 0.0% 5.0% 10.0% 15.0% 20.0% 25.0% ra psoriasis lupus infections ibd depression conjunctivitis cataracts asthma alopecia areata allergic rhinitis adhd c o m o rb id it ie s disclosures this study was sponsored by leo pharma.. the views expressed in this article are those of the author(s) and do not necessarily reflect the official policy or position of the department of the navy, department of defense, or the united states government. research data approved by naval medical center, portsmouth, va irb. i am a military service member. this work was prepared as part of my official duties. title 17 u.s.c. 105 provides that “copyright protection under this title is not available for any work of the united states government.” title 17 u.s.c. 101 defines a united states government work as a work prepared by a military service member or employee of the united states government as part of that person’s official duties. https://www.ncbi.nlm.nih.gov/pubmed/28577797 slide number 1 presented at fall clinical dermatology conference 2019 | las vegas, nv, usa | 17–20 october, 2019 previously presented at 28th eadv congress 2019 patients • ≥18 years of age with moderate to severe pso for ≥6 months, defined as pasi ≥12, ≥10% bsa affected and physician’s global assessment (pga) ≥3 on a 5-point scale. • candidates for systemic pso therapy, phototherapy, and/or photochemotherapy. • exclusion criteria: previous treatment with czp or >2 biologics; background • plaque psoriasis (pso) is an immune-mediated, inflammatory disease that is associated with significant physical and emotional burden.1 • psoriatic lesions located on visible areas of the body can have a major impact on patients’ quality of life (qol);2 psoriasis of the head and neck region in particular can cause a high degree of emotional distress, despite only representing 10% of the body surface area (bsa), and the greatest impact on qol is reported by female patients.2,3 • certolizumab pegol (czp) is a unique, fc-free, pegylated, anti-tumor necrosis factor approved by the fda and ema for the treatment of moderate to severe pso.4,5 • in phase 3 trials, czp has demonstrated significant improvements in the signs and symptoms of pso.6 • the psoriasis area and severity index (pasi), commonly used by physicians to assess the severity of pso, accounts for the size and character of psoriatic lesions across four body regions, one of which is the head and neck. • in this post-hoc analysis, we report czp efficacy for the head and neck region over 48 weeks. methods study design • data were pooled from the cimpasi-1 (nct02326298) and cimpasi-2 (nct02326272) phase 3 trials in adults with moderate to severe pso (figure 1). full study designs have been reported previously.6 • patients were randomized 2:2:1 to receive czp 400 mg every 2 weeks (q2w), czp 200 mg q2w (400 mg loading dose at weeks 0, 2 and 4), or placebo. • at week 16, patients receiving czp who achieved ≥50% improvement from baseline in pasi (pasi 50) continued to receive the same czp dose to week 48. references 1. who global report on psoriasis. available at: https://apps.who.int/iris/handle/10665/204417; 2. merola jf. et al. dermatol ther 2018;e12589; 3. timotijević zs. et al. acta dermatovenerol croat 2017;25:215–22; 4. certolizumab pegol prescribing information. available at www.fda.gov/drugs; 5. certolizumab pegol summary of product characteristics. available at www.ema.europa.eu/ema; 6. gottlieb ab. et al. jaad 2018;79:302–14.e6; 7. thaçi d. et al. acta derm venereol 2018;98, supp no. 219. author contributions substantial contributions to study conception/design, or acquisition/analysis/interpretation of data: pvdk, ap, mb, sk, jjc; drafting of the publication, or revising it critically for important intellectual content: pvdk, ap, mb, sk, jjc; final approval of the publication: pvdk, ap, mb, sk, jjc. author disclosures pvdk: received fees for consultancy service or lectureships from celgene, centocor, almirall, amgen, pfizer, philips, abbott, eli lilly, galderma, novartis, janssen, leo pharma, sandoz, bristol-myers squibb and dermavant ; ap: worked as an investigator and/or speaker and/or advisor for abbvie, almirall hermal, amgen, biogen idec, boehringer ingelheim, celgene, gsk, eli lilly, galderma, hexal, janssen, leo pharma, mc2, medac, merck serono, mitsubishi, msd, novartis, pfizer, tigercat pharma, regeneron, roche, sandoz biopharmaceuticals, schering-plough and ucb pharma; mb: employee of ucb pharma; sk: received fees for consultancy service from avexis, colorado prevention center, diamedica, puretech, ucb pharma, and zosano; jjc: received research/grant support from abbvie, amgen, boehringer ingelheim, janssen, lilly, mc2 therapeutics, merck & co., novartis, pfizer, regeneron, sandoz, sanofi, sun pharmaceuticals, ucb pharma and verrica pharmaceuticals; has served as consultant for abbvie, amgen, celgene, dermira inc., lilly, novartis, sun pharmaceuticals and ucb pharma; has worked on speakers bureau for abbvie, janssen, lilly, novartis, regeneron, sanofi, and ucb pharma. acknowledgements the studies were funded by dermira inc. in collaboration with ucb pharma. ucb is the regulatory sponsor of certolizumab pegol in psoriasis. we thank the patients and their caregivers in addition to the investigators and their teams who contributed to this study. the authors acknowledge bartosz łukowski, msc, ucb pharma, brussels, belgium for publication coordination and ruth le fevre, phd, costello medical, cambridge, uk for medical writing and editorial assistance. all costs associated with development of this poster were funded by ucb pharma. conclusions • rapid improvements in psoriasis of the head and neck region were seen as early as week 2 of czp treatment. • a higher proportion of patients treated with czp demonstrated a 75% or 90% improvement in pasi of the head and neck region at week 16 compared with placebo. improvements in czp-treated patients were maintained to week 48, indicating a durable clinical response in this hard-to-treat area. • the greatest improvements were observed for patients receiving czp 400 mg q2w. • these data suggest that czp may be a suitable treatment option for patients with moderate to severe pso affecting the head and neck, a known detractor from patients’ qol.7 objective • to report the efficacy of certolizumab pegol for psoriasis of the head and neck region in two phase 3 clinical trials. efficacy of certolizumab pegol for psoriasis of the head and neck in two phase 3 clinical trials: cimpasi-1 and cimpasi-2 p. van de kerkhof,1 a. pinter,2 m. boehnlein,3 s. kavanagh,4 j. j. crowley5 1radboud university medical centre, nijmegen, the netherlands; 2university hospital frankfurt, frankfurt, germany; 3ucb pharma, monheim, germany; 4ucb pharma, raleigh, nc, usa; 5bakersfield dermatology, bakersfield, ca, usa table 1. patient baseline characteristics czp 400 mg q2w (n=175) czp 200 mg q2w (n=186) placebo (n=100) age, years, mean (sd) 45.0 (12.9) 45.6 (13.2) 45.7 (13.8) male, n (%) 103 (58.9) 125 (67.2) 61 (61.0) bmi, kg/m2, mean (sd) 31.2 (7.9) 32.0 (7.8) 31.2 (7.4) prior biologic use, n (%) 59 (33.7) 62 (33.3) 29 (29.0) anti-tnf 39 (22.3) 44 (23.7) 19 (19.0) anti-il-17 8 (4.6) 16 (8.6) 5 (5.0) anti-il-12/il-23 10 (5.7) 3 (1.6) 6 (6.0) pso duration, years, mean (sd) 18.5 (12.6) 17.7 (12.9) 17.0 (12.6) pasi, mean (sd) 19.6 (7.3) 19.2 (7.2) 18.6 (6.6) head and neck score, meana 17.9 16.5 19.1 bsa affected, %, mean (sd) 23.6 (14.3) 23.5 (14.9) 23.1 (13.6) pga score, n (%) 3 (moderate) 126 (72.0) 128 (68.8) 72 (72.0) 4 (severe) 49 (28.0) 58 (31.2) 28 (28.0) aonly patients with head and neck involvement at baseline were included (czp 400 mg q2w: n=170; czp 200 mg q2w: n=169; placebo: n=93). bmi: body mass index; bsa: body surface area; czp: certolizumab pegol; il: interleukin; pasi: psoriasis area and severity index; pga: physician’s global assessment; pso: plaque psoriasis; q2w: every two weeks sd: standard deviation; tnf: tumor necrosis factor. czp: certolizumab pegol; ld: loading dose of czp 400 mg at weeks 0, 2 and 4 or weeks 16, 18 and 20; pasi: psoriasis area and severity index; q2w: every two weeks. figure 1. cimpasi-1 and -2 study design locf imputation. placebo data are shown to week 16 only; only 9 patients continued with placebo treatment through weeks 16–48. czp 200 mg q2w patients received a loading dose of czp 400 mg at weeks 0, 2 and 4. czp: certolizumab pegol; locf: last observation carried forward; pasi: psoriasis area and severity index; q2w: every two weeks. figure 3. percentage change from baseline in pasi of the head and neck region through weeks 0–48 estimates of responder rate reflect the simple average response across multiple imputed data sets, with missing data imputed using mcmc methodology. placebo data are shown to week 16 only; only 9 patients continued with placebo treatment through weeks 16–48. czp 200 mg q2w patients received a loading dose of czp 400 mg at weeks 0, 2, and 4. czp: certolizumab pegol; mcmc: markov chain monte carlo; pasi 75/90: psoriasis area and severity index 75% or 90% improvement of the head and neck region; q2w: every two weeks. figure 2. improvements in pasi of the head and neck region through weeks 0–48 a) pasi 75 b) pasi 90 • calculation of change from baseline included only patients with head and neck involvement. calculation of pasi 75 and pasi 90 responder rates included all randomized patients (patients without baseline head and neck involvement were considered non-responders). • for patients missing one or two severity measures (redness, thickness, or scaling) for the head and neck region at a given study visit, values were substituted with the mean of the measures available for that region at that visit. • patients who did not achieve pasi 50 at week 16 had their week 16 value carried forwards. patients who should have been mandatorily withdrawn from study treatment at week 32 or week 40 due to not achieving pasi 50 were treated as non-responders for subsequent visits with missing data. • estimates of responder rate reflect the simple average response across multiple imputed data sets, with missing data imputed using markov chain monte carlo (mcmc) methodology. continuous measures were imputed using last observation carried forward (locf). results patient demographics and baseline characteristics • 175, 186, and 100 patients were randomized to czp 400 mg q2w, czp 200 mg q2w and placebo, respectively, at week 0. patient baseline characteristics are shown in table 1. • baseline pasi of the head and neck region was comparable across czp 400 mg q2w, czp 200 mg q2w and placebo treatment groups (table 1). pasi of the head and neck region • at week 16, a higher proportion of patients receiving czp treatment achieved 75% and 90% improvements in pasi of the head and neck region compared with placebo (figure 2). • week 16 responder rates were maintained to week 48 for patients receiving both czp doses (figure 2). • mean percentage change from baseline in pasi of the head and neck region was also greater for czp-treated patients compared with placebo at week 16, and maintained to week 48 (figure 3). • although improvements were seen for both czp doses, responder rates were higher in patients receiving czp 400 mg q2w. history of primary failure to any biologic or secondary failure to >1 biologic; erythrodermic, guttate or generalized pso types; current or history of chronic or recurrent viral, bacterial or fungal infections. study assessments and statistical analyses • patients achieving a 75% and 90% improvement in psoriasis of the head and neck region, and the mean percentage change from baseline in head and neck pasi are reported, through weeks 0–48. 80 0 4424201612840 48 week r e sp o n d e r ra te ( % ) 60 40 100 20 40363228 69.2 16.2 78.8 65.1 76.6 czp 400 mg q2w (n=175) czp 200 mg q2w (n=186) placebo (n=100) 80 0 4424201612840 48 week r e sp o n d e r ra te ( % ) 60 40 100 20 40363228 56.3 9.9 69.7 55.6 67.9 -20 week p a s i h e a d a n d n e c k m e a n % c h a n g e f ro m b a se lin e 4424201612840 4840363228 -40 -60 -80 -100 0 czp 200 mg q2w (n=169) czp 400 mg q2w (n=170) placebo (n=93) -80.1 -2.8 -86.3 -76.5 -88.3 initial treatment period (double-blind) maintenance period (double-blind) <pasi 50 entered escape arm (czp 400 mg q2w) 0week 1:2:2 randomization 4832 40 czp 400 mg q2w 16 czp 200 mg q2wld <pasi 50 withdrawn <pasi 50 withdrawn <pasi 50 withdrawn ≥pasi 50 and <pasi 75: received ld then czp 200 mg q2w placebo q2w 12 acknowledgements: medical writing support was provided by prescott medical communications group (chicago, il) with financial support from ortho dermatologics; ortho dermatologics is a division of bausch health us, llc | presented at winter clinical dermatology conference 2020 • january 17-22, 2020 • kohala coast, hi synopsis ◾ acne is a common dermatologic issue in adolescence, though prevalence of acne in the adult population is increasing1 ◾ adult females are more likely to report acne than males across all age groups, with prevalence ranging from 50.9% (20-29 y) to 15.3% (≥50 y) in females and 42.5% (20-29 y) to 7.3% (≥50 y) in males2 ◾ adolescent and adult females are also more likely have worse acne-related quality of life3 ◾ a novel tazarotene 0.045% lotion formulation was developed for the treatment of acne, utilizing polymeric emulsion technology, resulting in a more uniform distribution of the active ingredient and hydrating excipients at the surface of the skin ◾ in a 12-week, randomized, double-blind, vehicle-controlled, parallel group, phase 2 study (nct02938494), tazarotene 0.045% lotion was superior to vehicle on inflammatory/ noninflammatory lesion count reductions in patients with moderate-to-severe acne4 ◾ in addition, tazarotene 0.045% lotion was as effective as the higher concentration tazarotene 0.1% cream (already approved for acne), but with fewer adverse events (aes)4 objective ◾ to evaluate the efficacy and safety of tazarotene 0.045% lotion in females and males methods ◾ in this phase 2 study, patients aged 12 years and older were randomized (2:2:1:1) to receive tazarotene 0.045% lotion, tazarotene 0.1% cream (tazorac), lotion vehicle, or cream vehicle • participants must have had a score of 3 (moderate) or 4 (severe) on the evaluator global severity score (egss) at the screening and baseline visit • in this study, cerave® hydrating cleanser and cerave® moisturizing lotion (l’oreal, ny) were provided as needed for optimal moisturization/cleaning of the skin ◾ a post hoc analysis was conducted in female and male patients, based on the following co-primary efficacy endpoints of the clinical trial: • mean absolute change in inflammatory and noninflammatory lesion counts from baseline to week 12 • treatment success, defined as percentage of patients achieving ≥2-grade reduction from baseline to week 12 in egss and a score of clear (0) or almost clear (1) ◾ safety and adverse events (aes) were also assessed results ◾ the intent-to-treat population included 210 participants (males, n=94; females, n=116) ◾ at week 12, tazarotene 0.045% lotion-treated females and males had significantly greater absolute least-squares mean reductions from baseline versus vehicle in noninflammatory lesion counts; only females had significant mean reductions versus vehicle in inflammatory lesion counts (figure 1) efficacy and safety of a novel tazarotene 0.045% lotion in females and males with moderate-to-severe acne table 1. treatment-emergent adverse events (safety population, pooled) males females participants, n (%) taz 0.045% lotion (n=31) tazorac 0.1% cream (n=30) combined vehicle (n=30) taz 0.045% lotion (n=37) tazorac 0.1% cream (n=41) combined vehicle (n=37) reporting any teae 6 (19.4) 9 (30.0) 4 (13.3) 4 (10.8) 10 (24.4) 5 (13.5) reporting any sae 0 0 0 0 0 0 discontinued due to teae 0 1 (3.3) 0 0 0 0 severity of teaes reported mild 5 (16.1) 6 (20.0) 4 (13.3) 1 (2.7) 6 (14.6) 5 (13.5) moderate 0 3 (10.0) 0 2 (5.4) 4 (9.8) 0 severe 1 (3.2) 0 0 1 (2.7) 0 0 relationship to study drug related 1 (3.2) 0 0 1 (2.7) 4 (9.8) 0 unrelated 5 (16.1) 9 (30.0) 4 (13.3) 3 (8.1) 6 (14.6) 5 (13.5) sae, serious adverse event; taz, tazarotene; teae, treatment-emergent adverse event. figure 1. mean change from baseline to week 12 in inflammatory and noninflammatory lesion counts in males and females (itt population, pooled) -16.5 -18.8 -13.8 -14.8 -30 -25 -20 -15 -10 -5 0 males females ls m e a n c h a n g e f ro m b a se li n e in�ammatory taz 0.045% lotion combined vehicle -21.6 -20.8 -12.0 -14.8 -30 -25 -20 -15 -10 -5 0 males females ls m e a n c h a n g e f ro m b a se li n e nonin�ammatory n=32 n=31 n=32 n=31n=37 n=38 n=37 n=38 *p<0.05 vs vehicle; **p<0.01 vs vehicle. itt, intent-to-treat; ls, least squares; taz, tazarotene. ◾ percent change from baseline in lesion counts by week are shown in figure 2 ◾ a larger percentage of tazarotene 0.045% lotion-treated females and males achieved treatment success versus vehicle (figure 3), although this difference was not significant ◾ there were no significant differences between the sexes on inflammatory/noninflammatory lesion counts or treatment success at week 12, regardless of treatment with tazarotene 0.045% lotion or tazarotene 0.1% cream ◾ treatment-emergent ae (teae) rates were higher in males than females for both tazarotene 0.045% lotion and tazarotene 0.1% cream; there were no differences with vehicle (table1) figure 3. percentage of males and females with treatment success at week 12a (itt population, pooled) 12.5% 24.3% 9.7% 10.5% 0 10% 20% 30% 40% males females p e rc e n ta g e o f p a rt ic ip a n ts n=32 n=31 n=37 n=38 taz 0.045% lotion combined vehicle apercentage of participants achieving ≥2-grade reduction from baseline to week 12 in egss and a score of clear (0) or almost clear (1). comparisons between taz 0.045% lotion and combined vehicle were not significant. egss, evaluator’s global severity score; itt, intent-to-treat; taz, tazarotene. conclusions ◾ tazarotene 0.045% lotion was well tolerated and effective versus vehicle in reducing inflammatory and noninflammatory lesion counts in females and noninflammatory lesion counts in males ◾ tazarotene 0.045% treated females had greater lesion count reductions and a greater percentage achieved treatment success than tazarotene-treated males, although these differences did not reach statistical significance ◾ taken together with the improved tolerability of tazarotene 0.045% lotion vs tazarotene 0.1% cream,4 this novel lotion formulation is a viable new treatment option that is as effective as cream with fewer aes references 1. skroza n, et al. j clin aesthet dermatol. 2018;11(1):21-25. 2. collier cn, et al. j am acad dermatol. 2008;58(1):56-9. 3. gorelick j, et al. j dermatol nurses assoc. 2015;7(3):154-162. 4. tanghetti ea, et al. j drugs dermatol. 2019;18(6):542. author disclosures dr. hilary baldwin has served as advisor, investigator, and on speakers bureau for almiral, foamix, galderma and ortho dermatologics. dr. lawrence green has served as speaker, consultant, or investigator for arcutis, abbvie, amgen, celgene, dermavant, jannsen, lilly, mc2, novartis, ortho dermatologics, sienna, sunpharma, and ucb. dr. leon kircik has acted as an investigator, advisor, speaker, and consultant for ortho dermatologics. dr. eric guenin is an employee of ortho dermatologics and may hold stock and/or stock options in its parent company. hilary baldwin, md1; lawrence green, md2; leon kircik, md3; eric guenin, pharmd, phd, mph4 1the acne treatment and research center, morristown, nj; 2department of dermatology, george washington university school of medicine, washington, dc; 3indiana university school of medicine, indianapolis, in; physicians skin care, pllc, louisville, ky; and icahn school of medicine at mount sinai, new york, ny; 4ortho dermatologics*, bridgewater, nj *ortho dermatologics is a division of bausch health us, llc. figure 2. percent change from baseline in inflammatory (a) and noninflammatory (b) lesion counts in males and females (itt population, pooled) -3.2% -11.4% -40.7% -56.5% -4.0% -21.1% -32.8% -52.9% -14.5% -24.3% -39.5% -48.7% -70% -60% -50% -40% -30% -20% -10% 0% # * ) ( ' & % " + , *# ** *) m e a n p e rc e n t c h a n g e f ro m b a se lin e males taz 0.045% lotion (n=32) tazorac 0.1% cream (n=31) combined vehicle (n=31) baseline week 2 week 4 week 8 week 12 a. in�ammatory lesion count b. nonin�ammatory lesion count -18.2% -30.6% -52.9% -70.1% -13.6% -33.6% -52.3% -65.4% -19.8% -28.3% -39.4% -53.6% -70% -60% -50% -40% -30% -20% -10% 0% # * ) ( ' & % " + , *# ** *) m e a n p e rc e n t c h a n g e f ro m b a se lin e females baseline week 2 week 4 week 8 week 12 -17.6% -25.9% -39.7% -54.1% -6.9% -22.0% -33.1% -49.9% -5.4% -4.6% -24.0% -28.2% -70% -60% -50% -40% -30% -20% -10% 0% # * ) ( ' & % " + , *# ** *) m e a n p e rc e n t c h a n g e f ro m b a se lin e males baseline week 2 week 4 week 8 week 12 -11.6% -26.7% -42.6% -59.2% -11.0% -26.9% -44.7% -57.2% -5.8% -16.3% -36.4% -40.9% -70% -60% -50% -40% -30% -20% -10% 0% # * ) ( ' & % " + , *# ** *) m e a n p e rc e n t c h a n g e f ro m b a se lin e females baseline week 2 week 4 week 8 week 12 taz 0.045% lotion (n=32) tazorac 0.1% cream (n=31) combined vehicle (n=31) taz 0.045% lotion (n=37) tazorac 0.1% cream (n=41) combined vehicle (n=38) taz 0.045% lotion (n=37) tazorac 0.1% cream (n=41) combined vehicle (n=38) statistical analyses were not performed between treatment groups. itt, intent-to-treat; taz, tazarotene. distribution of improvements in psoriasis area and severity index from the phase 2 trial of risankizumab in moderate to severe plaque psoriasis bruce strober, 1 kim a papp, 2 mary flack, 3 yihua gu, 4 elizabeth h z thompson, 5 wendell c valdecantos 4 1university of connecticut health center and probity medical research, farmington, ct, usa; 2k papp clinical research and probity medical research, waterloo, on, canada; 3boehringer ingelheim pharmaceuticals inc., ridgefield, ct, usa; 4abbvie inc., north chicago, il, usa; 5abbvie inc., redwood city, ca, usa introduction 1. papp ka, et al. n engl j med 2017; 376: 1551-60. objective • the objective of this analysis was to examine the distribution of pasi responses in patients from the phase 2 trial treated with risankizumab versus ustekinumab. materials & methods results conclusions • the overall improvements in pasi scores at weeks 12 and 16 were higher in patients treated with 90 or 180 mg risankizumab compared with ustekinumab. • patients treated with 90 or 180 mg risankizumab showed a greater shift in pasi distribution towards pasi 90-100 response rates compared with ustekinumab-treated patients. • risankizumab is a humanized igg1 monoclonal antibody that inhibits il-23 by binding its p19 subunit. in a phase 2 trial, risankizumab demonstrated superiority over ustekinumab in patients with moderate to severe plaque psoriasis.1 • response rates derived from dichotomizing a continuous variable at a certain threshold (eg, 90% improvement in psoriasis area and severity index, pasi 90) are often used as primary endpoints in clinical trials to demonstrate efficacy of investigational products. • however, additional visualization of the cumulative distribution of responses can help assess the consistency of pasi improvement at the population level. study design and patients • patients (n=166) with moderate to severe plaque psoriasis were randomized to receive subcutaneous injections of risankizumab (18 mg single dose, 90 or 180 mg at weeks 0, 4, and 16) or ustekinumab (45 or 90 mg, based on body weight at weeks 0, 4, and 16, figure 1). figure 1. study design of phase 2 trial of risankizumab in psoriasis patients references 16week 0 4 12 4824 = dose ra nd om is ed 1 :1 :1 :1 risankizumab 18 mg s.c.bn=43 n=40 ustekinumab 45/90 mg s.c.a risankizumab 180 mg s.c.n=42 n=41 risankizumab 90 mg s.c. 1o endpoint: pasi 90 at week 12 double-blind period (n=166) follow-upc a. used as per label (45 mg or 90 mg in patients with body weight ≤100 kg or >100 kg at randomization, respectively). b. placebo only at weeks 4 and 16. c. patients who failed to achieve at least 50% improvement from baseline in pasi (<pasi 50) during the follow-up period (indicated by gray shading), were eligible to enter the ole (nct02203851). abbreviations: pasi=psoriasis area and severity index; q12w=every 12 weeks; s.c.=subcutaneous. efficacy analyses • the proportions of patients achieving different levels of pasi responses were assessed at weeks 12 and 16 in an intent-to-treat population. • patients with a missing assessment were counted as non-responders for that assessment. • cumulative probability plots were generated to assess the distribution of changes from baseline in pasi score across treatment groups. • the proportions of patients achieving pasi 75, pasi 90, and pasi 100 responses are shown in figure 2. • at week 12, the proportions of patients achieving the primary end point of pasi 90 response were 30.2% (13/43), 73.2% (30/41), and 78.6% (33/42) for 18 mg, 90 mg, and 180 mg risankizumab groups, respectively, compared with 40% (16/40) for ustekinumab-treated patients (figure 2).1 figure 2. pasi 75, pasi 90, and pasi 100 response rates through week 16 (nri) week 0 week 4 week 8 week 12 week 16 0 10 20 30 40 50 60 70 80 90 100 pa tie nt s ac hi ev in g pa si 7 5 ( ) ustekinumab 45 90 mga (n 40) risankizumab 1 mga (n 43) risankizumab 90 mg (n 41) risankizumab 1 0 mg (n 42) 97.6 92.7 88.1 90.5 67.5 72.5 67.4 62.8 week 0 week 4 week 8 week 12 week 16 0 10 20 30 40 50 60 70 80 90 100 pa tie nt s a ch ie vi ng p a si 9 0 ( ) 73.2 78.0 78.6 81.0 42.5 40.0 48.8 30.2 week 0 week 4 week 8 week 12 week 16 0 10 20 30 40 50 60 70 80 90 100 pa tie nt s a ch ie vi ng p a si 1 00 ( ) 47.6 54.8 41.5 41.5 20.017.5 16.314.0 pasi 75 pasi 90 pasi 100 aone patient each with missing response in risankizumab 18 mg and ustekinumab 45/90 mg groups, and were imputed as non-responders. abbreviations: nri=non-responder imputation; pasi=psoriasis area and severity index. • patients treated with 90 mg or 180 mg of risankizumab achieved higher response rates across all levels of pasi improvement when compared with patients treated with 18 mg risankizumab (single dose) or ustekinumab (figure 3). figure 3. distribution of changes in pasi responses from baseline at weeks 12 and 16 (nri) w ee k 12 w ee k 16 pasi 100 pasi 90 <100 pasi 75 <90 pasi 50 <75 pasi 25 <50 pasi 0 <25 worsening 0 20 40 60 80 100 risankizumab 180 mg (n=42) risankizumab 90 mg (n=41) risankizumab 18 mga (n=43) ustekinumab 45/90 mga (n=40) percentage of patients 0 20 40 60 80 100 risankizumab 180 mg (n=42) risankizumab 90 mg (n=41) risankizumab 18 mga (n=43) ustekinumab 45/90 mga (n=40) percentage of patients a. one patient each with missing response in risankizumab 18 mg and ustekinumab 45/90 mg groups, and were imputed as having no (0%) improvement. abbreviations: nri=non-responder imputation; pasi=psoriasis area and severity index. figure 4. cumulative probability of percent change from baseline in pasi scores at weeks 12 and 16 (nri) • the cumulative probability plot demonstrated that patients treated with 90 or 180 mg of risankizumab had a higher likelihood of achieving greater improvements from baseline in pasi score compared with patients treated with 18 mg risankizumab or ustekinumab (figure 4). – median values for improvement in pasi scores at week 12 were 81.7%, 94.6%, and 98.8% in patients treated with 18 mg, 90 mg, and 180 mg of risankizumab, respectively, compared with 85.6% in ustekinumab-treated patients. – at week 16, median values for improvement in pasi scores were 87.4%, 97.5%, and 100.0% in patients treated with 18 mg, 90 mg, and 180 mg of risankizumab, respectively, compared with 87.0% in ustekinumab-treated patients. -100 -90 -80 -70 -60 -50 -40 -30 -20 -10 0 10 20 30 40 0 10 20 30 40 50 60 70 80 90 100 week 12 percent change from baseline in pasi score cu m ul ati ve p ro ba bi lit y risankizumab 1 mga risankizumab 90 mg risankizumab 1 0 mg ustekinumab 45 90 mga pa si 9 0 pa si 1 00 pa si 5 0 pa si 7 5 -100 -90 -80 -70 -60 -50 -40 -30 -20 -10 0 10 20 30 40 0 10 20 30 40 50 60 70 80 90 100 week 16 percent change from baseline in pasi score cu m ul ati ve p ro ba bi lit y pa si 9 0 pa si 1 00 pa si 5 0 pa si 7 5 pasi response mean 76.0% 72.3% 93.4% 88.6% median 85.6% 81.7% 94.6% 98.8% pasi response mean 77.8% 79.5% 93.1% 90.3% median 87.0% 87.4% 97.5% 100.0% b strober has received honoraria or fees for serving on advisory boards and as a consultant for abbvie, almirall, amgen, boehringer ingelheim, celgene, dermira, eli lilly, janssen-ortho, leo pharma, maruho, merck, novartis, pfizer, sanofi/regeneron, sun pharma, and ucb. he is a scientific director for the corrona-npf psoriasis registry. ka papp has received honoraria or fees for serving on advisory boards, as a speaker, as a consultant, grants as an investigator from abbvie, amgen, astellas, baxalta, baxter, boehringer ingelheim, bristol-myers squibb, celgene, dermira, eli lilly, forward pharma, galderma, genentech, glaxosmithkline, janssen, kyowa-hakko kirin, leo pharma, medimmune, merck-serono, merck sharp & dohme, novartis, pfizer, regeneron, roche, sanofi-genzyme, stiefel, sun pharma, takeda, ucb, and valeant. m flack is a full-time employee of boehringer ingelheim. y gu, ehz thompson, and wc valdecantos are full-time salaried employees of abbvie and may own stock/options. boehringer ingelheim funded the study (nct02054481), contributed to its design and participated in data collection. abbvie participated in data analysis and interpretation of the data, and in writing, review, and approval of the publication. medical writing support was provided by deepa venkitaramani, phd, of abbvie. a. one patient each with missing response in risankizumab 18 mg and ustekinumab 45/90 mg groups, and were imputed as having no (0%) improvement. abbreviations: nri=non-responder imputation; pasi=psoriasis area and severity index. disclosures presented at the fall clinical dermatology conference 36th anniversary • las vega, nevada • october 12 – 15, 2017 fc17posterabbviestroberdistributionofimprovements.pdf powerpoint presentation tralokinumab demonstrated a consistent safety profile with up to 42 months of treatment in moderate-tosevere atopic dermatitis: including adverse events of special interest kristian reich1, eric simpson2, richard langley3, richard b warren4, antonio costanzo5, hidehisa saeki6, peter almgren7, le gjerum7, anna carlsson7, melinda gooderham8, andreas pinter9, marjolein de bruin weller10, and andrew blauvelt11 1translational research in inflammatory skin diseases, institute for health services research in dermatology and nursing, university medical center hamburg-eppendorf, hamburg, de; 2department of dermatology, oregon health & science university, portland, or, usa; 3division of clinical dermatology and cutaneous science, dalhousie university, halifax, nova scotia, ca; 4dermatology centre, salford royal nhs foundation trust and nihr biomedical research centre, the university of manchester, manchester, uk; 5dermatology unit department of biomedical sciences, humanitas university, milano, it; skin pathology laboratory, humanitas research hospital irccs, milano, it; 6department of dermatology, nippon medical school, tokyo, jp; 7leo pharma a/s, ballerup, dk; 8skin centre for dermatology, peterborough, on, ca; department of dermatology, queen's university, kingston, on, ca; probity medical research, waterloo, on, ca; 9department of dermatology, venereology, and allergology, goethe-universität frankfurt am main, frankfurt am main, de; 10department of dermatology and allergology, university medical center utrecht, heidelberglaan 100, 3584 cx utrecht, nl; 11oregon medical research center, portland, or, usa table 1. ecztend interim analysis baseline demographic and disease characteristics table 2. aesis in ecztend at april 30, 2021 data cut-off conclusions • this analysis of 1442 patients with up to 42 months of treatment supports the long-term benefit-risk profile of targeted il-13 inhibition with tralokinumab for patients with moderateto-severe ad, with no new safety signals identified • exposure-adjusted incidence rates of aes of special interest were generally similar to or lower than rates reported during the short-term, placebo-controlled period up to week 16 and declined over time • overall, tralokinumab demonstrated sustained long-term improvement in extent and severity of atopic dermatitis over 104 weeks of treatment in ecztend figure 1. ecztend study design (a) and patient cohorts in interim analyses (b) objective to report an interim safety analysis of patients treated with tralokinumab for up to 42 months, including adverse events of special interest (aesi) materials and methods study design and patient cohorts • ecztend is an open-label, 5-year extension trial including adult and adolescent patients with ad in 11 countries who previously participated in the tralokinumab pts ecztra 1-8 or the traski investigatorinitiated study • in ecztend, patients received open-label tralokinumab 300 mg q2w (home use) plus optional topical corticosteroids (tcs), with visits every 8 weeks (figure 1a) • interim safety analyses presented here include all patients transferred from ecztra 1-5 and 7; with patients having received up to 42 months maximum tralokinumab exposure (≤1 year in pts and ≤2.5 years in ecztend; safety analysis set, n=1442) (figure 1b) • ecztra 1/2: double-blinded, randomized, placebo-controlled, 52-week monotherapy trials • ecztra 3: double-blinded, randomized, placebo-controlled, 32-week tcs combination trial • ecztra 4: open-label, 14-week, drug-drug interaction (ddi) trial • ecztra 5: double-blinded, randomized, placebo-controlled, 16-week, vaccine antibody-response trial • ecztra 7: randomized, double-blinded, placebo-controlled, 26-week tcs combination trial in cyclosporin a (csa) refractory patients • interim efficacy analyses are also presented from the ecztend week 104 cohort (n=616), which includes all patients who reached the 2-year time point or would have reached that time point had they not discontinued earlier (figure 1b) endpoints and analyses • primary endpoint: number of aes during the treatment period from baseline of ecztend up to week 268 • secondary endpoints: proportions of patients achieving an investigator’s global assessment (iga) score of 0/1 (clear/almost clear) and >75% improvement in eczema area and severity index (easi-75) from week 16 to week 248 • a summary of the number of aes, the rate of aes, the number (percentage) of patients with any treatment-emergent adverse events (teaes), deaths, saes, and withdrawals from the trial due to aes are presented • aesis were predefined in the trial based on areas of safety interest for monoclonal antibodies in ad: skin infections requiring systemic treatment, eczema herpeticum, malignancies, and eye disorders. other safety areas of interest were captured retrospectively using meddra searches of all aes results patients, demographics, and clinical characteristics • patients had up to 42 months of tralokinumab exposure (including pts plus ecztend) with a median time on tralokinumab total of 131.5 weeks (approximately 31 months; iqr 83.4-161.8 weeks), at the time of data cut-off • long-term use of tralokinumab 300 mg q2w was well-tolerated, and no new safety signals were identified with up to 42 months of treatment relative to initial treatment in parent trials (figure 2) • the pattern of frequently reported aes in ecztend (≥5.0% of patients) was similar to that observed with tralokinumab in the pts, including viral upper respiratory tract infection, atopic dermatitis, upper respiratory tract infection, headache, and conjunctivitis (reported by preferred term) • no events of conjunctivitis aes were saes; only 4 patients discontinued due to conjunctivitis aes (0.3 %) figure 2. long-term use of tralokinumab 300 mg q2w was well-tolerated in ecztend references 1. nutten s. ann nutr metab. 2015;66(suppl 1):8-16; 2. weidinger s, novak n. lancet. 2016;387:1109-22; 3. popovic b, et al. j mol biol. 2017;429:208-19; 4. wollenberg a, et al. br j dermatol. 2021;184(3):437-449; 5. silverberg ji, et al. br j dermatol. 2021;184(3):450-463; 6. blauvelt a, et al. j am acad dermatol. 2022;s0190-9622(22)02345-3.disclosures kristian reich has served as advisor and/or paid speaker for and/or participated in clinical trials sponsored by abbvie, almirall, amgen, boehringer ingelheim, bristol-myers squibb, celgene, forward pharma, gilead, galderma, janssen-cilag, kyowa kirin, leo, lilly, medac, novartis, ocean pharma, pfizer, sanofi, ucb; professor reich is co-founder of moonlake immunotherapeutics. eric simpson reports grants and/or personal fees from abbvie, boehringer ingelheim, celgene, dermavant, dermira, eli lilly, fortébio, galderma, incyte, kyowa kirin, leo pharma, medimmune, menlo therapeutics, merck, novartis, ortho dermatologics, pfizer, pierre fabre dermo cosmetique, regeneron, sanofi, tioga, and valeant. richard langley has served and received compensation in the form of grants and/or honoraria as principal investigator for and is on the scientific advisory board or has served as a speaker for abbvie, amgen, boehringer ingelheim, celgene, eli lilly, janssen, leo pharma, merck, novartis, pfizer, and ucb. richard b warren has received research grants or consulting fees from abbvie, almirall, amgen, arena, astellas, avillion, boehringer ingelheim, bristol myers squibb, celgene, dice, eli lilly, gsk, janssen, leo pharma, medac, novartis, pfizer, sanofi, sun pharma, ucb, and union. he is supported by the manchester nihr biomedical research centre. antonio costanzo has received research grants or consulting fees from abbvie, almirall, amgen, boehringer ingelheim, bristol myers squibb, celgene, eli lilly, janssen, leo pharma, novartis, pfizer, sanofi, ucb. hidehisa saeki has received lecture fees from kyorin, kyowa kirin, leo pharma, mitsubishi tanabe, maruho, sanofi, tokiwa, and taiho; and scholarship donations from esai, mitsubishi tanabe, maruho, and torii. peter almgren, le gjerum, and anna carlsson are employees of leo pharma. melinda gooderham has been an investigator, speaker and/or advisor for: abbvie, amgen, akros, anaptysbio, aslan, arcutis, bausch health, bms, boehringer ingelheim, celgene, dermira, dermavant, eli lilly, galderma, gsk, incyte, janssen, kyowa kirin, leo pharma, medimmune, merck, novartis, pfizer, regeneron, roche, sanofi genzyme, sun pharma, and ucb. andreas pinter has served as an investigator and/or speaker and/or advisor for abbvie, almirall-hermal, amgen, biogen idec, biontec, boehringer-ingelheim, celgene, celltrion, gsk, eli-lilly, galderma, hexal, janssen, leo pharma, mc2, medac, merck serono, mitsubishi, msd, novartis, pascoe, pfizer, tigercat pharma, regeneron, roche, sandoz biopharmaceuticals, sanofi-genzyme, schering-plough and ucb pharma. marjolein s. de bruin-weller is a consultant/advisor for abbvie, lilly, pfizer, regeneron, sanofi genzyme, and ucb and has received grant/research support from regeneron and sanofi genzyme. andrew blauvelt has served as a speaker, scientific adviser, and / or clinical study investigator for abbvie, abcentra, aligos, almirall, amgen, anaptysbio, arcutis, arena, aslan, athenex, boehringer ingelheim, bristol-myers squibb, dermavant, ecor1, eli lilly, evommune, forte, galderma, highlightii pharma, incyte, janssen, landos, leo pharma, merck, novartis, pfizer, rapt, regeneron, sanofi genzyme, sun pharma, ucb pharma, vibliome, and xencor. acknowledgements this analysis was sponsored by leo pharma a/s. medical writing according and editorial support from alphabet health by meredith whitaker, phd was funded leo pharma a/s, ballerup, denmark, to good publication practice guidelines (https://www.ismpp.org/gpp3). richard b warren is supported by the manchester nihr biomedical research centre. this work was previously presented at eadv 2022. scan to download a copy of this poster copies of this poster and its content, obtained through this qr code, are for personal use only and may not be reproduced without written permission from the authors introduction • atopic dermatitis (ad) is a chronic and debilitating inflammatory skin disease requiring long-term treatment options with a favorable safety profile1,2 • tralokinumab, a first-in-class, fully human monoclonal antibody, specifically neutralizes il-13 with high affinity3 • phase 3 studies with tralokinumab have demonstrated favorable safety and sustained efficacy in adult patients with ad for up to 1 year4,5 • an ongoing extension trial, ecztend (nct03587805), is assessing the safety and efficacy of treatment with subcutaneous tralokinumab 300 mg every 2 weeks (q2w) following participation in a parent trial (pt) • with one additional year added to the previously published data6 this analysis further describes the safety profile of tralokinumab during long-term treatment figure 3. aesis in ecztend at april 30, 2021 data cut-off summary of aesis in ecztend • aesis were observed at rates similar to or lower than reported in pts (figure 3, table 2) • the most frequent eye disorder was conjunctivitis, including bacterial, allergic and viral types • there was no clustering in type of malignancy and none reported in more than 2 patients • there was no specific clustering in any type of skin infection requiring systemic treatment • other areas of interest, based on common concerns for those with ad, were: • injection site reaction: reported for 35 patients [2.4%, 2.5 vs 22.9 and 4.0 (ne/pye)*100 in ecztend vs pt tralokinumab and placebo] • rates for herpes simplex, oral herpes and herpes zoster: similar or lower than placebo up to week 16 and rates decreased over time [2.0/1.6/1.3 vs 5.2/3.1/1.4 and 3.7/8.1/2.0 (ne/pye)*100 in ecztend vs pt tralokinumab and placebo] abbreviations %, percentage of patients with ≥1 event; ad, atopic dermatitis; adj., adjusted; ae, adverse event; aesi, adverse event of special interest; dlqi, dermatology life quality index; e, number of adverse events; easi, eczema area and severity index; iga, investigator’s global assessment; locf, last observation carried forward; n, number of patients with ≥1 event; ne, number of events; np, number of patients; nri, non-responder imputation; nrs, numeric rating scale; pye, patient-years of exposure; pt, parent trial; q2w, every 2 weeks; tcs, topical corticosteroids. figure 4. proportion of patients achieving easi-75, iga 0/1, worst weekly pruritus nrs ≤3, and dlqi ≤5 with tralokinumab at week 104 site visit. iga, easi, scorad, worst weekly pruritus nrs, eczema-related sleep nrs, patient use of topical treatment screening and follow-up visits home use training poem, dlqi/cdlqi, eq-5d-5l ada/pharmacokinetic measurement weeks from first treatment in ecztend 5640322416 484 8–2 0 screening period tcs use allowed visit schedule until end of may 2021b sfu 16 weeks after last imp 24864 72 80 88 96 1042 12 patient cohorts in ecztend interim analysis april 30, 2021 data cut-off all patients who reached the 2-year time point (week 104) or would have reached that time point had they not discontinued earlier week 104 efficacy cohort (n=616) all patients transferred from ecztra 1, 2, 3, 4, 5, and 7; up to 42 months maximum tralokinumab exposure (≤1 year in pts and ≤2.5 years in ecztend) safety analysis set (n=1442) ecztend interim safety analysis set n=1442 age median years (iqr) 38.0 (27.0; 50.0) sex n (%) male female 831 (57.6) 611 (42.4) race n (%)a white black asian 1093 (75.9) 108 (7.5) 203 (14.1) parent trial n (%) ecztra 1 ecztra 2 ecztra 3 ecztra 4 ecztra 5 ecztra 7 450 (31.2) 293 (20.3) 282 (19.6) 31 (2.1) 149 (10.3) 237 (16.4) age at onset of ad median years (iqr) 3.0 (1.0; 15.0) duration of ad median years (iqr) 27.0 (18.0; 39.0) patients who permanently discontinued ecztend n (%) 330 (22.9) parent trial baseline ecztend baseline iga severity n (%) clear/minimal (score=0/1) mild (score=2) moderate (score=3) severe (score=4) 765 (53.1) 677 (46.9) 442 (30.6) 524 (36.3) 391 (27.1) 85 (5.9) easi median (iqr) 26.8 (20.5; 37.6) 4.8 (1.7; 12.0) scorad median (iqr) 67.7 (60.0; 77.9) 30.2 (18.7; 45.0) dlqib median (iqr), n 16.0 (11.0; 22.0), 1391 5.0 (2.0; 10.0), 1400 worst weekly pruritus nrsc median (iqr), n 7.9 (6.8; 8.8), 1257 5.0 (3.0; 7.0), 1440 aavailable in 1440 patients. bsubjects from the ecztra 4 parent trial did not have dlqi assessments in the parent trial, and thus are missing parent trial baseline for dlqi assessments. cin pts, worst pruritus nrs is assessed daily; in ecztend, worst pruritus nrs is assessed based on recall of the previous week before the visit. a b placebo, n=680 tralokinumab, n=1605 tralokinumab, n=1442 up to week 16 parent trialsa ecztend data cutoff apooled safety analysis set includes patients from parent trials ecztra 1, 2, 3, 5, and phase 2b. brate calculated by number of events divided by pye, multiplied by 100. cfor pts, cochran-mantel-haenszel weights were applied to calculate adjusted ae incidences and rates to account for different randomization ratios across pts. dconjunctivitis reported by preferred term. n (%) 449 (67.2) 1080 (65.7) 1127 (78.2) 18 (2.8) 37 (2.1) 101 (7.0) 20 (2.8) 38 (2.3) 34 (2.4) eczema herpeticum malignancies skin infections requiring systemic treatment eye disorders [conjunctivitisd] placebo, n=680 tralokinumab, n=1605 tralokinumab, n=1442 up to week 16 parent trialsa ecztend data cutoff apooled safety analysis set includes patients from parent trials ecztra 1, 2, 3, 5, and phase 2b. brate calculated by number of events divided by pye, multiplied by 100. cfor pts, cochran-mantel-haenszel weights were applied to calculate adjusted ae incidences and rates to account for different randomization ratios across pts. dconjunctivitis category includes several preferred terms, such as conjunctivitis, conjunctivitis allergic, conjunctivitis bacterial and conjunctivitis viral. aes in ecztend interim safety analysis set aes up to week 16 in parent trials initial tralokinumab treatmenta tralokinumab q2w + optional tcs (n=1442; pye=2446.2; 131.5 weeks median exposure) tralokinumab q2w ± tcs (n=1605; pye=473.2) placebo q2w ± tcs (n=680; pye=193.1) n (%) rateb [(np/pye)*100] e rate [(ne/pye)*100] n (adj. %)c e adj. rateb,c [(ne/pye)*100] n (adj. %)c e adj. rateb,c [(ne/pye)*100] eczema herpeticum 17 (1.2) 0.7 18 0.7 6 (0.3) 6 1.2 10 (1.5) 10 5.2 malignancies 8 (0.6) 0.3 8 0.3 1 (0.1) 1 0.2 0 (0) 0 0 skin infections requiring systemic treatment 36 (2.5) 1.5 51 2.1 42 (2.6) 46 9.7 35 (5.5) 42 22.8 eye disorders 132 (9.2) 5.8 174 7.1 132 (7.9) 155 31.1 22 (3.4) 24 12.9 conjunctivitisd 125 (8.7) 5.4 160 6.5 126 (7.5) 145 29.0 21 (3.2) 23 12.3 keratoconjunctivitis 8 (0.6) 0.3 8 0.3 5 (0.3) 5 1.2 0 0 0 keratitis 6 (0.4) 0.2 6 0.2 4 (0.2) 5 0.9 1 (0.2) 1 0.6 • tralokinumab demonstrated sustained long-term improvement in ad signs and symptoms in patients who reached the 2-year time point (week 104), or would have reached that time point had they not discontinued earlier, prior to data cutoff april 30, 2021 (figure 4) summary of safety in ecztend • long-term use of tralokinumab 300 mg q2w was well-tolerated, and no new safety signals were identified with up to 42 months of treatment relative to initial treatment in parent trials (figure 2) 5.2 0 22.8 12.9 1.2 0.2 9.7 31.1 0.7 0.3 2.1 7.1 0 5 10 15 20 25 30 35 r a te [( n e / p y e )* 10 0 ]b ,c 6.5 29 12.3 n (%) 10 (1.5) 6 (0.3) 17 (1.2) 0 (0.0) 1 (0.1) 8 (0.6) 35 (5.5) 42 (2.6) 36 (2.5) 22 (3.4) 132 (7.9) 132 (9.2) pt ecztend apooled safety analysis set includes patients from parent trials ecztra 1, 2, 3, 5, and phase 2b. brate calculated by number of events divided by pye, multiplied by 100. cfor pts, cochran-mantel-haenszel weights were applied to calculate adjusted ae incidences and rates to account for different randomization ratios across pts. dconjunctivitis category includes several preferred terms, such as conjunctivitis, conjunctivitis allergic, conjunctivitis bacterial and conjunctivitis viral. sustained improvement in ad signs and symptoms data is relative to baseline in parent trial, n=616. nrs refers to worst weekly pruritis nrs ≤3. the observed analysis includes data for all participants with a valid measurement at the indicated timepoint. the locf method imputes the value recorded at the participant’s last visit for subsequent missed timepoints. the modified nri method considers participants who discontinue from trial due to adverse event(s) or lack of efficacy as non-responders, and other missing are imputed with locf. https://www.ismpp.org/gpp3 slide 1: tralokinumab demonstrated a consistent safety profile with up to 42 months of treatment in moderate-to-severe atopic dermatitis: including adverse events of special interest fc19 poster castle biosciences 3 cm_01_011.fcd 2019.accuracy metrics.v7 recurrence prediction in cutaneous melanoma with 31-gene expression profiling and sentinel lymph node biopsy graham litchman do1, ms, hillary caruso phd2, kyle covington phd2, robert cook phd2, darrell rigel md, ms3 1. national center for cutaneous melanoma 2. castle biosciences, inc. 3. new york university school of medicine background •the prognostic 31-gep test is an accurate predictor of metastatic risk for patients with cutaneous melanoma, stratifying patients into low (class 1a), intermediate (class 1b/2a), and high-risk (class 2b) 1-2. •previous prospective and retrospective studies have validated the 31gep as a strong predictor of risk of recurrence and distant metastasis, independent of other clinical and pathological features 2-7. •the test has demonstrated clinical utility in guiding patient management, including frequency of follow-up, use of imaging for surveillance, and referral for interdisciplinary care 8-12. •use of the 31-gep to guide sentinel lymph node biopsy (slnb) decisions has recently been validated, such that patients with t1-t2 melanoma over the age of 55 with a gep class 1a result have a very low probability of sln positivity and favorable outcomes11. to perform a comparative evaluation of the prognostic accuracy of the 31-gep and sentinel lymph node biopsy. objective references & acknowledgments conclusions and significance • these results show that the 31-gep detects more patients with high-risk melanoma than slnb and combining both achieves best sensitivity. • the high npv of the 31-gep test assures that patients with low-risk results have low probability of metastasis or death from melanoma. • use of 31-gep to guide slnb decisions does not alter the sensitivity of combined 31-gep and sln status on prognosis. funding & disclosures this study was sponsored by castle biosciences, inc. hc, kc, and rc are employees and options holders of castle biosciences, inc. gl is a fellow of the national society for cutaneous medicine which receives grants from castle biosciences. dsr served as a consultant to castle biosciences, inc.. methods results • we evaluated the prognostic accuracy of the 31-gep and slnb in a cohort of 1479 patients comprised of 3 previously described cohorts4-6 and a novel cohort of stage i-iii cutaneous melanoma cases collected from 7 institutions under an irb-approved protocol. • we also compared the sensitivity and npv of 31-gep and slnb in a model which assumed use of the 31-gep to triage patients for slnb. gep sln gep and sln rfs n=1479 n=867 n=1479 sensitivity 76% (71-80%) 57% (51-63%) 86% (82-90%) specificity 76% (73-78%) 74% (70-77%) 69% (66-72%) ppv 46% (42-50%) 50% (44-56%) 43% (41-45%) npv 92% (90-94%) 79% (75-82%) 95% (93-96%) dmfs n=1223 n=867 n=1223 sensitivity 76% (70-82%) 61% (55-68%) 88% (83-92%) specificity 69% (66-72%) 72% (68-75%) 60% (57-63%) ppv 35% (31-39%) 39% (34-44%) 32% (30-34%) npv 93% (91-95%) 86% (83-89%) 96% (94-97%) mss n=1157 n=630 n=1157 sensitivity 86% (77-92%) 72% (60-80%) 94% (87-98%) specificity 65% (62-68%) 67% (64-70%) 57% (54-60%) ppv 17% (13-20%) 16% (13-21%) 15% (14-16%) npv 98% (97-99%) 96% (95-98%) 99% (98-100%) variable all cases (n=342) age, median (range) 61 (18-94) breslow thickness, mm median (range) 1.2 (0.1-29) ulceration present 346 (23.4%) ajcc stage i 852 (57.6%) ii 313 (21.1%) iii 312 (21.1%) table 1. demographics of the 1479 patients in study table 2. accuracy metrics of gep and sln only patients with reported end points were included in analysis. patients from greenhaw, et. al. did not have dmfs or sln status reported. patients from hsueh, et. al. did not have mss reported. accuracy metrics of combined tests determined for patients who had positive sln or gep class 2 result. study design n novel cohort archival, multi-center 211 gastman et al.4 archival, multi-center 690 greenhaw et al.6 prospective, single center 256 hsueh et al.5 prospective, multi-center 322 1. gerami et al. clin cancer res 2015;21:175-83. 2. gerami et al. j am acad dermatol 2015;72:780-5 e783. 3. zager et al. bmc cancer 2018;18(1):130. 4. gastman et al. jaad 2019;80(1):149-157. 5. hsueh et al. j hematol oncol 2017;10:152. 6. greenhaw et al. dermatol surg 2018; dec;44(12):1494-1500. 7. keller et al. cancer med 2019. apr.5 doi:10.1002/cam4.2128. 8. berger et al. curr med res opin 2016;32(9):1599-1604 9. dillon et al. j cut med 2018;2(3):111-121 10. schuitevoerder et al. j drugs dermatol 2018;17(2)196-199 11. vetto et al. future oncol. 2019 apr;15(11):1207-1217. 12. burman, et al. skin. 2019 sept; 3(5): 291-306. t1-t2 t3-t4 age <55 age ≥ 55 and class 1b, 2a, 2b age ≥ 55 and class 1a gep result sln status gep result gep result sln status all ages table 2. sensitivity and npv of 31-gep and slnb in a model assuming use of 31-gep to guide slnb decisions gep sln gep and sln rfs n=1479 n=842 n=1479 sensitivity 76% (71-80%) 56% (50-62%) 84% (79-88%) npv 92% (90-94%) 79% (75-82%) 94% (93-95%) dmfs n=1223 n=842 n=1223 sensitivity 76% (70-82%) 61% (53-68%) 86% (80-90%) npv 93% (91-95%) 86% (83-89%) 95% (94-97%) mss n=1157 n=609 n=1157 sensitivity 86% (77-92%) 72% (60-82%) 94% (97-98%) npv 98% (97-99%) 96% (95-98%) 99% (98-100%) skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 71 short communications distinguishing features: linear rashing is not always koebnerization nneamaka c. ezekwe, md1, thy huynh, md2, robert t. brodell, md3,4 1school of medicine, university of mississippi medical center, jackson, ms 2department of dermatology university of mississippi medical center jackson, ms 3professor and chair, department of dermatology, professor, department of pathology university of mississippi medical center, jackson, ms 4instructor in dermatology, university of rochester school of medicine and dentistry, rochester ny both cutaneous sarcoidosis and psoriasis can present with thick white scaling in a linear array. distinguishing these conditions will alter the treatment plan. sarcoidosis is a chronic inflammatory, multisystem disease of unknown etiology. cutaneous involvement occurs in 25% of patients. immunopathologically, it is characterized by a macrophage/th1/th17 cell-mediated, non-caseating,granulomatous inflammatory process.cutaneous sarcoidosis has a predilection for scars associated with trauma, tattoos, piercings, acne, and herpes zoster. scar sarcoidosis produces thick, indurated, erythematous to violaceous dermal papules or nodules, and assumes the shape of linear scars. the classical presentation are well-healed flat scars that suddenly elevate, however, this can occur as early as a few months to as long as 59 years after an injury (figure 1).1 when a cutaneous site is susceptible to infections, tumors, and immune disorders because of dysregulated local neuromodulator signaling, it can be termed an immunocompromised district.2 there may be vascular, neural, or biochemical features inherent in scars that represent fertile ground for sarcoidal granulomas to develop. psoriasis is a chronic autoimmune disorder associated with activated t cells that drive a hyperplastic, inflammatory, proliferative response through elaboration of th1/th17 cytokines, stimulating keratinocyte to produce micaceous scaling and salmon coloration. in 25% of patients, psoriasis arises in a scratch or wound, producing raised, red linear, scaling plaques termed koebnerization (figure 2).3 this occurs within 7 to 14 days after injury. when psoriatic lesions clear, there are often no visible scars. linear sarcoidosis is not the result of koebnerization as has been suggested. 4,5,6 koebnerization occurs within days or weeks as a result of inflammation induced by trauma. sarcoidosis occurs many months to decades after trauma in uninflamed, completely healed scars. table 1 summarizes the features that distinguish introduction distinguishing features skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 72 figure 1. (a) linear sarcoidosis suddenly arising in a previously well-healed scar. (b) linear psoriasis arising on the left posterior shoulder due to excoriation of pruritic patches. (used with permission from the international journal of dermatology, volume 52. issue 10, pages 1282-1284) linear cutaneous sarcoidosis from linear psoriasis. routine histological examination distinguishes cutaneous sarcoidosis from psoriasis. sarcoidosis demonstrates islands of naked epithelioid granulomas surrounding lymphocytes and scattered multinucleated giant cells. patients with new onset cutaneous sarcoidosis should undergo diagnostic testing (ocular examination, chest x-ray, pulmonary function tests, kveim tests, serum ace levels, and liver function tests) to rule out systemic involvement. psoriasis is largely a clinical diagnosis based on the nature and distribution of the scaling plaques. histopathology demonstrates acanthosis, hyperkeratosis, neutrophilic spongiform pustules, and parakeratosis in the absence of serum. cosmetically disfiguring, symptomatic, ulcerating, or progressively worsening cutaneous sarcoidosis is treated with intralesional corticosteroid therapy as firstline treatment. if local therapy fails, systemic glucocorticoids, antimalarial agents, and methotrexate are often effective. anti-tnf biologic agents and thalidomide can be used in refractory cases (table 1). for limited plaque psoriasis arising in a scar, topical corticosteroids and emollients are first-line therapy. alternatives include tar, topical retinoids, topical vitamin d, and anthralin. for facial or intertriginous areas, calcineurin inhibitors are useful corticosteroid sparing agents. intralesional steroids, systemic agents (table 1), and phototherapy are recommended for moderate to severe psoriasis. evaluation treatment a. b. skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 73 table 1: features distinguishing linear cutaneous sarcoidosis from linear (koebnerized) psoriasis psoriasis sarcoidosis pathophysiology (general) th1/th17 cell-mediated inflammatory process in the region of the dermal-epidermal junction macrophage/th1/th17 cellmediated, non-caseating, granulomatous infiltrate in the dermis that extends into the subcutaneous fat pathophysiology of appearance in trauma related events koebnerization, an isomorphic response immunocompromised district, an isotonic response time of onset of linear lesions relative to trauma within 7 to 14 days after injury delayed appearance 6 months to 59 years after injury lesion types well-demarcated, raised, red plaques with white scaling centralized in a scar thick, indurated, erythematous to violaceous dermal macules, papules, and solid or annular plaques affecting a single color in a tattoo and/or suddenly appearing in well-healed scars pathology epidermal hyperproliferation and abnormal differentiation of epidermal keratinocytes with chronic inflammation noncaseating, chronic granulomas affecting multiple organs, including the skin possible associated systemic involvement psoriatic arthritis with joint pain and metabolic syndrome systemic multi-organ involvement treatment topical/intralesional corticosteroids (5-10mg/cc), phototherapy, calcineurin inhibitors, and systemic agents including retinoids, methotrexate, cyclosporine, apremilast, and biologic immune modifying agents intralesional corticosteroids (510mg/cc), systemic glucocorticoids, antimalarial agents (hydroxychloroquine and chloroquine), methotrexate, anti tnf agents, and thalidomide cutaneous sarcoidosis and psoriasis can present with linear scaled patches. mechanical trauma (koebnerization) occurs in psoriasis, whereas, the linear lesions of sarcoidosis appear in well-healed scars (immunocompromised district). the distinct pathophysiologic basis of these conditions is associated with clinical and histopathologic distinguishing features. conflict of interest disclosures: nneamaka c. ezekwe and thy huynh have no conflicts of interest to report. robert brodell discloses the following potential conflicts of interest: research has been performed for glaxo smith kline, novartis and galderma laboratories. advisory boards: intraderm pharmaceuticals. funding: none corresponding author: robert t. brodell, md 2500 north state street department of dermatology jackson, ms 39216 phone: 601-815-8000 fax: 601-984-1150 email: rbrodell@umc.edu conclusion mailto:rbrodell@umc.edu skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 74 references: 1. huynh tn, jackson jd, brodell rt. tattoo and vaccination sites: possible nest for opportunistic infections, tumors, and dysimmune reactions. clin dermatol. 2014;32(5):678-684. doi:10.1016/j.clindermatol.2014.04.016 2. ruocco v, brunetti g, puca r v., ruocco e. the immunocompromised district: a unifying concept for lymphoedematous, herpes-infected and otherwise damaged sites. j eur acad dermatology venereol. 2009;23(12):1364-1373. doi:10.1111/j.1468-3083.2009.03345.x 3. bhagavathula n, nerusu kc, fisher gj, et al. amphiregulin and epidermal hyperplasia: amphiregulin is required to maintain the psoriatic phenotype of human skin grafts on severe combined immunodeficient mice. am j pathol. 2005;166(4):1009-1016. doi:10.1016/s00029440(10)62322-x 4. hiroaki u. scar sarcoidosis can be an expression of the isomorphic response of koebner against the scar. kawasaki med j. 2001;27(2):67-73. 5. ghorpade a. sarcoidosis presenting as psoriasiform koebnerized papules in an indian male. int j dermatol. 2013;52(10):1282-1284. doi:10.1111/j.1365-4632.2011.05155.x 6. ueki h. koebner phenomenon in lupus erythematosus with special consideration of clinical findings. autoimmun rev. 2005;4(4):219223. doi:10.1016/j.autrev.2004.11.007 skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 543 research letters factors influencing patient satisfaction in dermatology abigail cline, phd, md1, tamar gomolin, bsc2, bijan safai, md1 1department of dermatology, new york medical college school of medicine, new york, ny 2new york medical college school of medicine, valhalla, ny enhancing patient experience and engagement may improve clinical outcomes.1 patient satisfaction often serves as a proxy for quality of medicine, with physicians evaluated and reimbursed based on patient satisfaction scores. in the field of dermatology, patient satisfaction plays a very important role since traditional markers of quality, such as mortality and hospital readmission rates, are not reasonable measures of patient care. patient satisfaction scores are one of the most accessible markers insurance companies abstract background: patient satisfaction is a proxy for healthcare quality, with physicians evaluated and reimbursed based on patient satisfaction scores. despite the growing influence of patient satisfaction, factors that impact patient satisfaction in dermatology remain unclear. methods: we analyzed 225 responses to an online survey evaluating patient expectations, willingness, and satisfaction regarding dermatology appointments. patient willingness and satisfaction were measured on a 1-5 likert scale. results: respondents were most willing to discuss their condition and to be examined with a dermatoscope. respondents were least willing to wear a patient gown without underwear and to be photographed. highly satisfying factors included a written treatment plan, provider medication recommendations, and use of gloves during physical exams. highly dissatisfying factors included waiting 60 minutes, taking off underwear with a patient gown, and being photographed with a cellphone. patient willingness and satisfaction differed significantly by gender and age. male respondents reported less satisfaction than female respondents if a nurse explained the treatment plan. older respondents were significantly more willing to change into a patient gown, to be photographed, to be examined with a dermatoscope, and to undergo a biopsy than younger respondents. older and female respondents preferred written plans, wh ile younger and male respondents preferred verbal plans. younger respondents reported higher satisfaction with an email follow-up compared to older respondents, who preferred a phone call. conclusion: these findings may represent relatively easy ways to improve patient satisfaction scores. further insight into factors affecting patient satisfaction may enhance patient experience and engagement, thereby improving clinical outcomes. introduction skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 544 and prospective patients can use to evaluate dermatologists. the field of dermatology recognizes the importance of patient satisfaction, with the american board of dermatology encouraging the collection of patient satisfaction survey data during the maintenance of certification process.2 despite the growing research in patients’ perceptions of their visits, factors that enhance patient satisfaction remain unclear. while one study found that a patient’s perception of the character of the physician directly affects patient satisfaction scores, others have found that environmental factors such as the physician spending a few more minutes with the patient and even the physician sitting down when talking to patients, were relatively easy ways to improve satisfaction scores.3-6 however, many of these previous studies were limited by their research methods. one was limited to online patient reviews, which may select towards very positive or negative opinions.4 others were limited to reviews concerning only one dermatology clinic or one hospital system.5,6 the goal of this study is evaluate factors related to patient satisfaction with dermatology clinic appointments. respondents completed a survey assessing patient expectations, willingness, and satisfaction regarding dermatology appointments. to objectively understand factors affecting patient satisfaction, respondents were surveyed independent of their dermatological care using an online survey platform. after institutional review board approval, an online survey was distributed to individuals older than 18 years-of-age who reported having seen a dermatologist within the past year and having a working knowledge of english. overall, 225 participants completed the survey via redcap (nashville, tn), after recruitment through amazon's mechanical turk (amazon, seattle, wa), an online crowdsourcing platform extensively used by psychologists for participant recruitment.7 the survey evaluated patient satisfaction using a 1 (no satisfaction) to 5 (a lot of satisfaction) likert scale. results were analyzed overall, by age (18-39 years old versus 40 and older), and by gender (female versus male). statistics included χ2 tests and student’s t-tests. a total of 225 subjects completed the survey (table 1). results were analyzed overall, and by demographic groups, including age (18-39 years old versus 40 and older) and gender (female versus male). overall, satisfaction declined with longer wait times (p<0.001), changing into a patient gown before meeting the dermatologist (p<0.001), and removing underwear (p<0.001) (table 1). older patients preferred changing into a gown before meeting the dermatologist, while younger patients preferred the dermatologist to present them with the choice to wear a gown (p<0.05). older patients also showed a strong preference toward keeping underwear on compared to younger patients (p<0.05). female patients preferred to be given the choice whether to change into a gown (p<0.05) and to keep underwear on (p<0.001) as compared to male patients. satisfaction was higher with use of gloves as compared to bare hands (p<0.001) and with taking pictures using a camera as compared to a cellphone (p<0.001) (table 1). older respondents reported higher satisfaction with whole body examination methods results skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 545 table 1. factors related patient satisfaction before, during, and after the clinic visit satisfaction factors before the visit overall (n=225) age 18-39 (n=152) age >40 (n=73) female (n=140) male (n=85) 10 min wait 3.0* 3.0 3.0 3.1 3.0 30 min wait 1.9* 1.9 1.8 1.9 1.9 60 min wait 1.5* 1.5 1.3 1.5 1.5 putting on patient gown before meeting the dermatologist 2.7 2.6* 2.9* 2.8 2.7 patient decides whether to put on patient gown 3.7* 3.7 3.7 3.8* 3.5* keeping underwear on with patient gown 3.7* 3.6* 3.9* 3.9* 3.3* removing underwear with patient gown 2.0 2.1 1.9 2.0 2.2 satisfaction factors during the visit overall age 18-39 age >40 female male examining only the area of concern 3.4 3.5* 3.2* 3.3 3.5 examining the whole body 3.3 3.2* 3.6* 3.4 3.2 touching the skin with bare hands 2.4* 2.3 2.5 2.3 2.5 touching the skin with gloves 4.0* 3.9 4.1 4.0 3.9 examining with dermatoscope 3.9 3.7* 4.1* 3.9 3.9 taking pictures with cellphone 2.1* 2.3* 1.9* 2.0* 2.3* taking pictures with camera 3.3* 3.2* 3.6* 3.4 3.3 performing a skin biopsy 3.5 3.4* 3.8* 3.6 3.4 satisfaction factors after the visit overall age 18-39 age >40 female male patient medication recommendations 3.8* 3.8 3.8 3.8 3.6 physician medication recommendations 4.1* 4.0* 4.3* 4.2 4.0 verbal treatment plan 4.3 4.2* 4.5* 4.3 4.2 written treatment plan 4.3 4.2* 4.5* 4.3 4.2 scheduled follow-up 3.9* 3.8* 4.1* 4.0* 3.8* follow-up as needed 3.4* 3.5* 3.2* 3.3 3.6 calling the patient after the appointment 3.9 3.8 4.0 3.9 3.8 emailing the patient after the appointment 3.9 4.0 3.8 4.0 3.8 (p<0.01), use of dermatoscope (p<0.05), and skin biopsies as compared to younger ones (p<0.05). younger patients reported higher satisfaction having only the area of concern examined (p<0.05) and having pictures taken with a cellphone (p<0.05) as compared to older patients. male respondents reported higher satisfaction with having pictures taken with a cellphone as compared to female respondents (p<0.05). satisfaction was higher when physicians presented definitive medication recommendations as compared to offering patients a range of medication options (p<0.001) and was higher when follow-ups were scheduled in advance as compared to being left to occur as needed (p<0.001) (table 1). older respondents preferred verbal (p<0.05) and written (p<0.01) instructions, and scheduled follow-ups (p<0.05) as compared to younger patients. younger respondents preferred scheduling a skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 546 follow-up as needed (p<0.05). female patients preferred scheduled follow-ups (p<0.05) as compared to male patients. overall, the highest satisfying factors included verbal instructions, written instructions, and definitive medication recommendations. factors rated as the most satisfying differed by age and gender. older and female patients preferred written instructions, while younger and male respondents preferred verbal instructions. factors related to dissatisfaction did not differ by age or gender. factors related to dissatisfaction included long wait times, underwear removal, pictures taken using a cellphone, and use of bare hands during the exam. these results may elucidate relatively simple ways to improve patient satisfaction scores. patient satisfaction differed significantly by gender and age, thereby making it more difficult to implement general measures for quality improvement. limitations of this study include the potential for sampling bias associated with the use of an online survey sample. nonetheless, this study does overcome common limitations of previous research: the data is not constrained to self-selected online patient reviews, the results are not limited to one dermatological clinic or hospital system, and patients are not being surveyed immediately after appointments, where added pressure can affect responses.5,6,8 taking these findings in a holistic way may shed light on broader principles that clinicians can apply in myriad heretofore undiscussed areas of their practice. it is important to realize that these preferences do not exist as isolated data points, but as markers illustrating broader trends in patient desires. for example, the universal preferences for photography using a dedicated camera rather than a cellphone and for a physician’s use of gloves are both consistent with a patient desire for an encounter that is more formal than casual. similarly, the clear preference patients have against removing underwear is consistent with feelings of physical and psychological vulnerability that is oft discussed by medical ethicists, but perhaps not adequately addressed by practitioners. the cognizant physician may then extrapolate from this to find other things in the examination or treatment routine that may be improved upon. by contrast, the marked differences relating to how treatment plans are communicated are illustrative of the very real and significant differences in preferred communication styles that other disciplines have long recognized.9 it is perhaps of less significance exactly which demographic groups showed which preferences, than it is that such variation in preferences exists, affects satisfaction, and ought to be accommodated. these findings point to relatively easy ways to improve patient satisfaction scores. although, the influence of patient experience on overall quality of care is complex and context-dependent, improvements in this realm can be made without jeopardizing other measures of quality. dermatologists can implement these straightforward changes to enhance patient experience, with the goal of improving clinical outcomes. conflict of interest disclosures: none funding: none discussion conclusion skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 547 corresponding author: abigail cline, phd, md department of dermatology metropolitan hospital 1901 first avenue new york, ny 10029 phone: 336-671-9027 email: aecline25@gmail.com references: 1. camacho f, balkrishnan r, khanna v, khanna k, feldman sr. how happy are dermatologists’ patients. the dermatologist. 2013;21(4). 2. 2. moc requirements https://www.abderm.org/diplomates/fulfilling-mocrequirements/moc-requirements.aspx#sa. 3. 3. kincey j, bradshaw p, ley p. patients' satisfaction and reported acceptance of advice in general practice. the journal of the royal college of general practitioners. 1975;25(157):558-566. 4. 4. uhas aa, camacho ft, feldman sr, balkrishnan r. the relationship between physician friendliness and caring, and patient satisfaction: findings from an internet-based survey. the patient. 2008;1(2):91-96. 5. 5. patel s, sutton av, thorpe j, tsai ky, crew ab. patient satisfaction and quality of care: a prospective study at outpatient dermatology clinics. cutis. 2018;102(1):33-35. 6. 6. de salins ca, brenaut e, misery l, roguedas-contios am. factors influencing patient satisfaction: assessment in outpatients in dermatology department. journal of the european academy of dermatology and venereology : jeadv. 2016;30(10):1823-1828. 7. 7. buhrmester m, kwang t, gosling sd. amazon's mechanical turk: a new source of inexpensive, yet high-quality, data? perspectives on psychological science : a journal of the association for psychological science. 2011;6(1):3-5. 8. 8. ali st, feldman sr. patient satisfaction in dermatology: a qualitative assessment. dermatology online journal. 2014;20(2). 9. 9. pashler h, mcdaniel m, rohrer d, bjork r. learning styles: concepts and evidence. psychological science in the public interest : a journal of the american psychological society. 2008;9(3):105-119 https://www.abderm.org/diplomates/fulfilling-moc-requirements/moc-requirements.aspx#sa https://www.abderm.org/diplomates/fulfilling-moc-requirements/moc-requirements.aspx#sa • at week 64, 72.1% (n = 44), 31.1% (n = 19), and 13.1% (n = 8) of the patients who were retreated after relapse achieved pasi 75, pasi 90, and pasi 100 responses, respectively (figure 2) figure 2. rate of a) pasi 50, b) pasi 75, c) pasi 90, and d) pasi 100 responders over time by treatment condition in part 3 of resurface 1 a) b) c) d) plot shows data from weeks 32–64 of part 3, resurface 1. pasi, psoriasis area and severity index; pbo, placebo; til, tildrakizumab. 32 36 40 44 48 52 56 60 64 0 20 40 60 80 100 pasi 50 weeks p a s i 5 0 r es po nd er s, % continuous til 100 mg (n = 135) pbo, no relapse (n = 52) pbo, relapse (n = 61) 32 36 40 44 48 52 56 60 64 0 20 40 60 80 100 pasi 75 weeks p a s i 7 5 r es po nd er s, % continuous til 100 mg (n = 135) pbo, no relapse (n = 52) pbo, relapse (n = 61) 32 36 40 44 48 52 56 60 64 0 20 40 60 80 100 pasi 90 weeks p a s i 9 0 r es po nd er s, % continuous til 100 mg (n = 135) pbo, no relapse (n = 52) pbo, relapse (n = 61) 32 36 40 44 48 52 56 60 64 0 20 40 60 80 100 pasi 100 weeks p a s i 1 00 r es po nd er s, % continuous til 100 mg (n = 135) pbo, no relapse (n = 52) pbo, relapse (n = 61) • table 2 compares median (q1, q3) pasi scores for patients who did not relapse upon rerandomization to placebo, relapsed upon rerandomization to placebo and were retreated, or received continuous tildrakizumab 100 mg table 2. median absolute pasi scores of patients by treatment condition and time point during part 3 of resurface 1 week 28 week 52 week 64 pbo, no relapse (n = 52) 0.8 (0.0, 3.2) 2.6 (0.8, 5.2) 4.0 (2.0, 7.4) continuous til 100 mg, no relapse (n = 108) 1.0 (0.0, 2.2) 1.0 (0.0, 2.4) 1.2 (0.0, 3.0) baseline week 28 time of relapse pbo, relapse (n = 61) 20.3 (14.3, 22.9) 0.8 (0.0, 2.2) 11.0 (8.6, 16.2) numbers are median (q1, q3). pasi, psoriasis area and severity index; pbo, placebo; q1, first quartile; q3, third quartile; til, tildrakizumab. • of 116 patients who were continuously treated with tildrakizumab 100 mg in part 3, 6.9% (n = 8) relapsed after week 28 — seven patients relapsed on a single visit; 10 patients missed a single visit — the remaining 108 patients completed the study with a median (q1, q3) pasi score of 1.2 (0.0, 3.0) (table 2) results • at study initiation, 309 patients were randomized to tildrakizumab 100 mg • at week 28, a total of 229 patients receiving tildrakizumab 100 mg who achieved pasi ≥75 were rerandomized to receive placebo (n = 113) or continue tildrakizumab 100 mg (n = 116) • baseline demographics and disease characteristics were similar between patients rerandomized at week 28 (part 3) compared with patients who were randomized to tildrakizumab 100 mg at study initiation (week 0, part 1) (table 1) table 1. resurface 1 baseline demographics and disease characteristics til 100 mg arm, baseline (n = 309) til 100 mg arm, week 28 pasi 75 responders rerandomized in part 3 (n = 229) sex, male, n (%) 207 (67.0) 148 (64.7) age, years 46.4 ± 13.1 46.4 ± 13.4 race, white, n (%) 217 (70.2) 172 (75.1) weight, kg 88.5 ± 23.9 88.8 ± 23.3 bsa, % 29.7 ± 17.4 28.7 ± 17.1 pasi score 20.0 ± 7.9 19.6 ± 7.6 pga >3 308 (99.7) 228 (99.6) data are mean ± standard deviation unless otherwise indicated. bsa, body surface area; pasi, psoriasis area and severity index; pga, physician’s global assessment; til, tildrakizumab. • of the 113 patients rerandomized to placebo, 54.0% (n = 61) relapsed and were retreated by week 64; 5 patients missed a single visit • median (q1, q3) time to relapse was 238 (167, 294) days; no patient experienced rebound • of the patients who were retreated, 59 completed part 3 out to week 64; 2 discontinued prior to week 64 — duration of retreatment was measured from the start of retreatment to either week 64 or discontinuation date for patients who completed part 3 or discontinued during part 3, respectively • the mean (standard deviation) and median (q1, q3) duration of retreatment was 92.7 (58.6) days and 85.0 (56, 141) days, respectively • among 51 patients with ≥12 weeks of retreatment data, median (q1, q3) time to regain response was 28 (28, 48) days — of these patients, 49 (96.1%) regained response in <12 weeks; 2 (3.9%) patients regained response after >12 weeks of retreatment • after 4 (n = 51), 8 (n = 46), and 12 weeks (n = 33) of retreatment, median (q1, q3) pasi scores were 5.9 (3.3, 10.0), 3.2 (1.8, 5.9), and 2.7 (0.8, 4.6), respectively (figure 1) figure 1. median absolute pasi scores after relapse and retreatment with tildrakizumab 100 mg values on x-axis represent number of weeks after retreatment in patients who relapsed upon rerandomization to placebo. error bars represent first and third quartiles. pasi, psoriasis area and severity index; q1, first quartile; q3, third quartile. efficacy and safety of tildrakizumab 100 mg for plaque psoriasis in patients randomized to treatment continuation vs treatment withdrawal with retreatment upon relapse in resurface 1 wendy cantrell,1 patricia lee,2 alan m mendelsohn,3 jeff parno,3 stephen j rozzo,3 wilson liao4 1village dermatology, birmingham, al, usa; 2center for clinical studies, webster, tx, usa; 3sun pharmaceutical industries, inc., princeton, nj, usa; 4department of dermatology, university of california san francisco, san francisco, ca, usa introduction • tildrakizumab is a high-affinity, humanized, immunoglobulin g1κ, anti–interleukin-23p19 monoclonal antibody approved in the us, europe, and australia for the treatment of moderate to severe plaque psoriasis • two large, phase 3, randomized, controlled trials (resurface 1, nct01722331; and resurface 2, nct01729754) of tildrakizumab were conducted in patients with moderate to severe chronic plaque psoriasis1 — tildrakizumab significantly improved psoriasis response rates vs placebo measured with the psoriasis area and severity index (pasi) responses (pasi 75, pasi 90, and pasi 100) and physician’s global assessment (pga), by week 12 (primary endpoint) and week 28 (secondary endpoint) — tildrakizumab was well tolerated with low frequencies of serious adverse events (aes) and discontinuations due to aes2 • treatment efficacy in patients who discontinue medication, relapse, and are retreated is important for clinical practice objective • to assess residual disease in plaque psoriasis in patients successfully treated with tildrakizumab 100 mg who interrupted treatment, relapsed, and were retreated vs continuously treated patients in a post hoc analysis of the phase 3 resurface 1 trial methods study design • resurface 1 was a 3-part, double-blind, randomized, controlled, 64-week phase 3 study in adult patients with moderate to severe plaque psoriasis1 • participants ≥18 years with moderate to severe chronic plaque psoriasis (body surface area ≥10%, pga ≥3, pasi ≥12) were eligible • the base study consisted of 3 parts: — in part 1 (weeks 0–12), patients were randomly assigned (1:2:2) to blinded administration of subcutaneous placebo or tildrakizumab 100 or 200 mg at weeks 0 and 4 — in part 2 (weeks 12–28), patients previously receiving placebo were rerandomized to tildrakizumab 100 or 200 mg, administered at weeks 12 and 16 and then every 12 weeks. patients receiving tildrakizumab received a placebo injection at week 12 to maintain the blinded treatment, then received the same dose of tildrakizumab at week 16 and then every 12 weeks ○ at week 28, tildrakizumab nonresponders (those who did not achieve pasi ≥50) discontinued treatment ○ tildrakizumab responders (pasi ≥75) and partial responders (pasi ≥50 and <75) continued the study — in part 3 (weeks 28–64), patients who had received tildrakizumab from the start of the study were rerandomized to placebo, tildrakizumab 100 mg, or tildrakizumab 200 mg based on their level of response to treatment; patients received tildrakizumab every 12 weeks or placebo every 4 weeks — after rerandomization to placebo, treatment was reinitiated if patients experienced a relapse (a reduction in maximum pasi response by ≥50%) or a rebound (>125% worsening of pasi scores from baseline values) ○ this analysis focuses on the tildrakizumab 100 mg responders (patients who achieved ≥75% relative improvement in pasi score from baseline) who were rerandomized at week 28 to receive either placebo or continue tildrakizumab 100 mg ○ responders who were rerandomized to placebo were retreated with tildrakizumab 100 mg at relapse, 4 weeks later, and then every 12 weeks populations analyzed • this analysis was performed on tildrakizumab 100 mg patients with a pasi 75 response at week 28 who either continued tildrakizumab 100 mg treatment or received placebo in part 3 • patients who received >1 dose of treatment after week 28 and those retreated for ≥12 weeks were included in efficacy analyses efficacy • residual disease was assessed as median (first quartile [q1], third quartile [q3]) pasi scores, scale 0–72, every 4 weeks through week 64 • relative clinical improvement was evaluated as proportion of patients who achieved 75%, 90%, or 100% pasi improvement from baseline or a pga of 0 or 1 (with >2-point decrease from study baseline) • time to loss and to regain efficacy were calculated as median (q1, q3) number of days • missing data were imputed using last observation carried forward method — no relapse designations were attributed to missed visits safety • for analysis of tildrakizumab safety only, both pasi 75 responders and partial responders at week 28 were included • aes were evaluated every 4 weeks through week 64; all analyses were performed as observed safety • of the 135 patients (pasi 75 responders and partial responders) who continued to receive tildrakizumab 100 mg, 128 (94.8%) patients completed 64 weeks of the study; 7 (5.2%) patients discontinued — reasons for discontinuation were withdrawal by subject (1.5%), ae (0.7%), lost to follow-up (0.7%), noncompliance with study drug (0.7%), physician decision (0.7%), and protocol violation (0.7%) • of the 113 patients randomized to placebo at week 28, 103 (91.2%) completed the study, and 10 (8.8%) discontinued — reasons for discontinuation were withdrawal by subject (4.4%), lost to follow-up (2.6%), ae (0.9%), and other protocolspecified criteria (0.9%) • incidence of tier 1 aes (defined as severe infections [any infection that was a serious ae or required intravenous antibiotics], malignancies [excluding carcinoma in situ of the cervix], nonmelanoma skin cancer, melanoma skin cancer, confirmed extended major adverse cardiovascular events, and drug-related hypersensitivity reactions) in patients rerandomized to placebo or tildrakizumab is shown in table 3 table 3. tier 1 adverse events by preferred term at week 28 rerandomized to til 100 mg (n = 135a) rerandomized to pbo (n = 113) at least one tier 1 ae 3 (2.2%) 2 (1.8%) basal cell carcinoma 1 (0.7%) 1 (0.9%) bowen’s disease 1 (0.7%) 0 carcinoma in situ of skin 1 (0.7%) 0 sinusitis 1 (0.7%) 0 cerebellar infarction 0 1 (0.9%) aincludes subjects who were partial responders at week 28. ae, adverse event; pbo, placebo; til, tildrakizumab. • two tier 1 aes occurred in 1.8% (n = 2) of the 113 responders rerandomized to placebo after week 28 who did not relapse (cerebellar infarction and basal cell carcinoma) • of the 135 patients rerandomized to tildrakizumab 100 mg after week 28 (including partial responders), 2.2% (n = 3) reported 4 tier 1 aes (basal cell carcinoma, bowen’s disease, carcinoma in situ of the skin, and sinusitis) • no tier 1 aes were reported in patients who were rerandomized to placebo at week 28 and relapsed either on placebo or tildrakizumab 100 mg conclusions • in part 3 of the resurface 1 trial (weeks 28–64), tildrakizumab 100 mg had a durable response profile — a large proportion (46%) of tildrakizumab 100 mg responders did not relapse after rerandomization to placebo for 48 weeks after receiving their last dose of drug • in patients who relapsed upon tildrakizumab withdrawal and were retreated, residual disease resolved in the majority of cases within a median of 28 days after receiving tildrakizumab 100 mg, and the rate of aes was low • continuation of tildrakizumab 100 mg was associated with low residual disease and a low rate of aes references 1. reich k, et al. lancet. 2017;390:276–88. 2. blauvelt a, et al. br j dermatol. 2018;179:615–22. acknowledgments we thank patients for their participation. the studies were funded by merck sharp & dohme corp., a subsidiary of merck & co., inc., kenilworth, nj, usa. analyses were funded by sun pharmaceutical industries, inc., princeton, nj, usa. editorial support was provided by puneet dang, phd, of alphabiocom, llc, and funded by sun pharmaceutical industries, inc. disclosures wc has no disclosures on file. pl has served as an investigator for merck. amm is an employee of sun pharmaceutical industries, inc.; and has individual shares in johnson and johnson, and as part of retirement account/mutual funds. jp is an employee of sun pharmaceutical industries, inc.; and has served as statistical consultant for sun pharmaceutical industries, inc.; and kyowa kirin pharmaceutical development, inc. sjr is an employee of sun pharmaceutical industries, inc. wl has conducted research funded by abbvie, amgen, janssen, novartis, pfizer, and regeneron/sanofi. presented at fall clinical dermatology conference for pas & nps 2020, april 3–5, orlando, fl, usa 0 2 4 6 8 10 12 14 16 weeks after retreatment p a s i sc or e , m ed ia n (q 1, q 3) 0 (n = 61) 4 (n = 51) 8 (n = 46) 12 (n = 33) weeks after retreatment pa s i s co re , m ed ia n (q 1, q 3) weeks pa s i 5 0 re sp on de rs , % pasi 50 weeks pa s i 7 5 re sp on de rs , % pasi 75 weeks pa s i 9 0 re sp on de rs , % pasi 90 weeks pa s i 1 00 r es po nd er s, % pasi 100 acknowledgements: medical writing support was provided by prescott medical communications group (chicago, il) with financial support from ortho dermatologics; ortho dermatologics is a division of bausch health us, llc | presented at winter clinical dermatology conference 2020 • january 17-22, 2020 • kohala coast, hi synopsis ◾ onychomycosis—a chronic fungal nail infection—can occur in children, ranging in prevalence from 0.35% – 5.5% worldwide1 ◾ onychomycosis has been reported to be responsible for approximately 15% of all nail dystrophies in children2 ◾ treatment of onychomycosis is challenging, and can require systemic antifungals for prolonged periods of time; however, parents and healthcare practitioners are hesitant to use long-term systemic treatments in children3 ◾ efinaconazole 10% topical solution (jublia® ortho dermatologics, bridgewater, nj) is an azole antifungal indicated for the topical treatment of onychomycosis of the toenails due to trichophyton rubrum and trichophyton mentagrophytes objective ◾ to evaluate efinaconazole 10% topical solution in pediatric patients with onychomycosis methods ◾ this phase 4, multicenter, open-label study evaluated safety, pharmacokinetics (pk), and efficacy of efinaconazole 10% topical solution in pediatric patients with distal lateral subungual onychomycosis ◾ efinaconazole was administered once daily for 48 weeks, with a 4-week posttreatment follow up at week 52 ◾ participants were aged 6 – 16 years with culture-positive mild-to-severe onychomycosis affecting ≥20% of at least 1 great toenail ◾ the pk subset was patients 12 – 16 years with moderate-to-severe onychomycosis affecting ≥50% of each great toenail and onychomycosis in ≥4 additional toenails ◾ the primary objective of this study was evaluation of safety and pk • safety included adverse events (aes) and serious aes (saes) • pk assessments included area under the concentration time curve from 0 to 24 hours (auc0 -24 ), maximum plasma concentration (cmax ), and time to cmax (tmax ); pk parameters were assessed based on blood samples collected on days 28 and 29 (predose and up to 24 hours postdose) ◾ efficacy assessments included mycologic cure, complete cure, and clinical efficacy results study population ◾ a total of 62 patients were enrolled in the study; of these, 12 (19.4%) patients did not complete the study (withdrawal by parent/guardian, n=6; lost to follow-up, n=5; participant request, n=1) safety, pharmacokinetics, and efficacy of efinaconazole 10% topical solution for the treatment of onychomycosis in pediatric patients pharmacokinetics ◾ the final pk analysis population comprised 15 patients; 2 patients were not included (samples arrived thawed from facility [n=1] and statistical outlier [n=1]) ◾ the concentration-time profiles for efinaconazole and the h3 metabolite were relatively stable, with only minor fluctuations during the 24-hour dosing interval (figure 1) ◾ systemic exposure to efinaconazole was low (table 2) ◾ based on mean auc0-24 in molar amounts, exposure to the h3 metabolite was approximately 5-fold higher than that observed for efinaconazole (0.169 versus 0.0327 nmol*h/ml) figure 1. mean efinaconazole and h3 metabolite plasma concentration-time profiles after topical administration of efinaconazole solution on day 28 (pk analysis population) 0 0.25 0.5 0.75 1.0 1.25 1.5 1.75 2.0 ! # 4 &# #( m e a n p la sm a c o n ce n tr a ti o n ( n g /m l) time (hours) e�naconazole (n=15) h3 metabolite (n=15) 0 2 4 12 24 table 2. mean pharmacokinetic parameters of efinaconazole and h3 metabolite after topical administration of efinaconazole solution on day 28 (pk analysis population) efinaconazole (n=15) h3 metabolite (n=15) tmax , median (range), h 12.0 (0.00 – 24.5) 4.05 (0.00 – 24.5) cmax , mean (sd), ng/ml 0.549 (0.375) 1.65 (1.31) auc0-24 , mean (sd), ng*h/ml 11.4 (7.68)a 38.1 (30.4)b an=11; bn=13. auc0-24 , area under the concentration time curve from 0 to 24 hours; cmax , maximum plasma concentration; sd, standard deviation; tmax , time to maximum plasma concentration. ◾ sixty participants administered ≥1 dose of study drug (safety population), 17 of whom had pk data on days 28 and 29 (pk population) ◾ in the safety population, mean age was 13.4 years (range: 6 – 16 years), 66.7% were male, and 88.3% were white ◾ in the pk population, mean age was 14.1 years (range: 12 – 16 years), 64.7% were male, and 100% were white safety ◾ a summary of all treatment-emergent aes (teaes) is shown in table 1 ◾ all teaes were mild or moderate and none led to study discontinuation ◾ the only treatment-related teae was ingrowing nail, with 8 events in 2 participants (table 1) ◾ no treatment-related saes were reported ◾ no safety signals or trends associated with local skin reactions were observed table 1. treatment-emergent adverse event summary (safety population) efinaconazole solution (n=60) number of teaes, no. 99 participants with ≥1 teae, n (%) 38 (63.3) participants with ≥1 treatment-emergent sae, n (%) 1 (1.7)a most common teaes (>5% in safety population), n (%) nasopharyngitis 18 (30.0) headache 6 (10.0) influenza 5 (8.3) tinea pedis 4 (6.7) contusion 4 (6.7) nail injury 4 (6.7) ingrowing nail 4 (6.7) treatment-related teae, n (%) ingrowing nail 2 (3.3) athe sae of pneumonia was deemed unrelated to treatment; the moderate event resolved with hospitalization and did not require a change in study drug application. sae, serious adverse event, teae, treatment-emergent adverse event. efficacy ◾ by week 52, 65.0% of patients achieved mycologic cure, with a 36.7% mycologic cure rate observed as early as week 12 (figure 2) ◾ a total of 40.0% of patients had complete cure by week 52 (figure 3), and half of patients achieved clinical efficacy by study end (figure 4) figure 2. mycologic cure (safety population, locf) 0% 25% 50% 75% 100% ! #( p e rc e n ta g e o f p a rt ic ip a n ts study visit (weeks) e�naconazole 10% (n=60) 0 12 36 48 5224 0% 36.7% 70.0% 70.0% 65.0% 53.3% mycologic cure was defined as negative potassium hydroxide (koh) and negative fungal culture. locf, last observation carried forward. figure 3. complete cure (safety population, locf) 0% 25% 50% 75% 100% ! #( p e rc e n ta g e o f p a rt ic ip a n ts study visit (weeks) e�naconazole 10% (n=60) 0 12 36 48 5224 0% 0% 8.3% 35.0% 40.0% 0% complete cure was defined as 0% clinical involvement of the target toenail and mycologic cure (negative koh and negative fungal culture). locf, last observation carried forward. lawrence f eichenfield, md1; boni elewski, md2; jeffrey l sugarman, md, phd3; ted rosen, md4; aditya gupta, md, phd5; radhakrishnan pillai, phd6; tina lin, pharmd7 1departments of dermatology and pediatrics; university of california, san diego school of medicine and rady children’s hospital, san diego, ca; 2university of alabama at birmingham school of medicine, birmingham, al; 3university of california, san francisco, ca; 4baylor college of medicine, houston, tx; 5mediprobe research inc., london, on, can and university of toronto, toronto, on, can; 6bausch health us, llc*, petaluma, ca; 7ortho dermatologics*, bridgewater, nj *bausch health us, llc is an affiliate of bausch health companies inc. ortho dermatologics is a division of bausch health us, llc. figure 4. clinical efficacy (safety population, locf) 0% 25% 50% 75% 100% ! #( p e rc e n ta g e o f p a rt ic ip a n ts study visit (weeks) e�naconazole 10% (n=60) 0 12 36 48 5224 0% 0% 18.3% 43.3% 50.0% 8.3% clinical efficacy was defined as affected target great toenail area <10%. locf, last observation carried forward. conclusions ◾ efinaconazole 10% topical solution administered once daily for a year was well tolerated in this pediatric population ◾ the systemic exposure to efinaconazole in this pediatric population was comparable to that previously reported in adults (cmax , 0.67 ng/ml; auc0-24 , 12.15 ng*h/ml)4 ◾ efinaconazole was efficacious in pediatric patients, with improved mycologic cure (65%) and complete cure (40%) rates compared with adults from two 1-year studies (mycologic cure: 53.4–55.2%; complete cure: 15.2–17.8%)4 references 1. gupta ak, et al. pediatr dermatol. 2018;35(5):552-559. 2. rodriguez-pazos l, et al. mycoses. 2011;54(5):450-453. 3. eichenfield lf, friedlander sf. j drugs dermatol. 2017;16(2):105-109. 4. prescribing information. jublia® (efinaconazole) topical solution, 10%. ortho dermatologics. author disclosures le has served as investigator and consultant for ortho dermatologics. be has provided clinical research support (research funding to university) for abbvie, anaptysbio, boehringer ingelheim, bristol myers squibb, celgene, incyte, leo, lilly, merck, menlo, novartis, pfizer, regeneron sun, ortho dermatologics, vanda; and as consultant (received honorarium) from boehringer ingelheim, celgene, leo, lilly, menlo, novartis, pfizer, sun, ortho dermatologics, verrica. js is a consultant for ortho dermatologics, bausch health, regeneron, sanofi, and pfizer. tr has served as consultant for ortho dermatologics. ag has served as consultant, speaker, and investigator for ortho dermatologics. rp is an employee of bausch health us, llc and may hold stock and/or stock options in its parent company. tl is an employee of ortho dermatologics and may hold stock and/or stock options in its parent company. skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 571 brief articles palmoplantar pityriasis rosea aurel apple, ba 1, ann lin, do, angela kim, do, mph2, suzanne rozenberg, do2, rachel kushner, do2 1new york institute of technology college of osteopathic medicine, port jefferson, ny 2department of dermatology, st. john’s episcopal hospital, far rockaway, ny pityriasis rosea (pr) is characterized by a papulosquamous rash with minimal constitutional symptoms. atypical variants of pr are less easily recognized and constitute about 20% of all reported cases, thus formulating a thorough differential diagnosis is critical in making a proper diagnosis.1,2 many atypical variants of pr have been described including vesicular, unilateral, and inverse pr.3 we describe a 48-year-old male who presented following a traumatic motor vehicle accident with an atypical presentation of palmoplantar pr which mimicked secondary syphilis. a 48-year-old man with fitzpatrick type iv skin presented with a rash of 2 days duration on his lower back, that spread to his upper back, legs, thighs, arms, neck and torso. he reported right knee abrasion following a pedestrian versus vehicle mva that he self-treated with triple antibiotic ointment on the right knee. the area then became red, itchy and expanded. he denied any recent viral illnesses or systemic symptoms. the patient reports monogamous sexual activity with wife for the past few decades. denies any other sexual encounters. physical exam showed erythematous papules and plaques with collarettes of scales on the patient’s neck, arms, back, thighs, legs and buttocks (figure 1). a large erythematous scaly plaque was noted on the either side of the right knee, the site of mva injury (figure 2). the initial diagnosis of pr was made and no initial treatment was provided due to the asymptomatic nature of the skin rash. at the two-week follow up the papulosquamous rash became even more widespread, with more prominent scale and erythema. moreover, dusky, erythematous, scaly papules and plaques were seen on the palms and soles, raising suspicion for secondary syphilis (figure 3). labs for rpr, cbc, cmp, and hiv as well as two punch biopsies were taken from the patient’s left upper posterior thigh and right lateral knee with the request for spirochete staining. rpr, with reflex titer and confirmatory testing, was non-reactive and hiv testing was negative. biopsy of the left upper posterior thigh and right lateral knee showed hyperkeratosis, irregular epidermal hyperplasia, focal mounds of parakeratosis, spongiosis and perivascular inflammatory introduction case presentation skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 572 figure 1. diffuse erythematous scaly papules and plaques with collarette of scales on the back. figure 2site of abrasion from mva. lesion with peripheral scale expanded after application of triple antibiotic ointment. figure 3erythematous scaly papules and plaques on the palms. infiltrate of lymphocytes cuffing around the vessels. a few extravasated rbcs were noted as well as presence of focal exocytosis of lymphocytes within the epidermis. silver staining was negative for spirochetes and pas was negative for fungal hyphae. the final pathology diagnosis read “mild spongiotic dermatitis possible pityriasis rosea; a drug or viral exanthem is not excluded.” pityriasis rosea (pr) has been widely documented in literature as an acute papulosquamous skin rash, most commonly affecting children and young adults. its etiology remains uncertain, but it’s believed to be of viral origin.4 typically, pr will first manifest with a “herald patch” which is larger and more conspicuous than later eruptions.1 histopathological examination of these lesions shows focal parakeratosis, mild acanthosis, mild spongiosis, papillary dermal discussion skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 573 edema with perivascular infiltrates of lymphocytes and histiocytes and focal extravasation of the rbcs.1, 5 figure 4. punch biopsy from left upper posterior thigh. mild spongiosis in epidermis with mounds of parakeratosis above the stratum corneum. sparse papillary dermal lymphocytes, perivascular inflammation with lymphocytes. some extravasated erythrocytes are seen. silver stain negative for spirochetes. (h&e, 4x) atypical presentations of pr are differentiated by their varying morphology, size, distribution, number, site, severity, and course.1 our case was atypical in its site of involvement and in its course. our patient presented with widespread erythematous scaly papules and plaques with palmoplantar involvement. palmoplantar pr is minimally documented to our knowledge. different variants of palmoplantar pr have been reported, the first being bukhari who called for palmoplantar involvement to be included among the known variant forms of pr.6 lesions of secondary syphilis may appear similarly to palmoplantar pr but would also be associated with systemic symptoms such as genital-mucosal involvement and lymphadenopathy.7 we ruled out syphilis with a non-reactive rapid plasma reagin (rpr) test. no additional treponemal testing was performed as the patient did not have health insurance. however, rpr may be negative in syphilis patients with a high treponemal load or with concomitant hiv in prozone effect, but our patient denied any history of sexually transmitted infection and hiv test was negative.8 we performed two punch biopsies of papulosquamous lesions on the patient’s left upper posterior thigh and right lateral knee.8 biopsies of both the left upper posterior thigh and the right lateral knee revealed patterns more consistent with pr, and silver staining failed to detect any spirochetes. additionally, our patient may have exhibited the koebner phenomenon, which is the extension of disease process to unaffected skin that is usually preceded by trauma.9 while first described in psoriasis, it has since been reported in other diseases including pr.9,10 nwabudike presented a case suggesting pr due to koebner phenomenon occurring at a site of a routine blood draw in a 35-year-old female patient.9 similar to nwabudike case, we conjectured this phenomenon possibly occurred in our patient.9 the largest initial lesion on our patient’s right knee may have been the herald patch that erupted post-traumatically and/or secondary to allergic contact dermatitis to the triple antibiotic cream. our patient’s negative history of a recent viral illness, often an inciting factor for eruptions of pr, further suggests this alternate explanation of his pr onset by the koebner phenomenon. other possible causes of pr in our patient include an id reaction from allergic contact dermatitis of the knee at the original application site of triple antibiotic ointment. the differential diagnoses for papulosquamous palmoplantar lesions conclusion skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 574 include secondary syphilis, palmoplantar psoriasis, dyshidrotic dermatitis, and tinea manus. if clinical history suggest secondary syphilis given a negative rpr, more specific lab results could be obtained. treponemal tests are more specific, which include fluorescent treponemal antibody absorption (fta-abs), microhemagglutination test for antibodies to t. pallidum (mha-tp) and several others. furthermore, koebner phenomenon resulting in pr, although not well documented, should be considered as potential instigating factor and may contribute to further understandings of this process. acknowledgements: special thanks and dermatopathology image credits to sjeh department of pathology, sadaf sheikh, m.d. and bridge dermatopathology, paul chu, m.d. conflict of interest disclosures: none funding: none corresponding author: aurel apple, ba college of osteopathic medicine institute/university/hospital: new york institute of technology 25 seaside drive port jefferson, ny 11777 phone: 631-848-6477 e-mail: aapple@nyit.edu references: 1. kumarasamy rrp. papular pityriasis rosea with palmar involvement an atypical presentation. university journal of medicine and medical specialties 2017; 3(4). 2. chuh a, zawar v, leet a. atypical presentations of pityriasis rosea: case presentations. journal of the european academy of dermatology and venereology 2005; 19: 120-126. 3. deng y, li h, chen x. palmoplantar pityriasis rosea: two case reports. journal of the european academy of dermatology and venereology 2006; 21(3). 4. stulberg dl, wolfrey j. pityriasis rosea. american family physician 2004; 69: 87–91. 5. okamoto h, imamura s, aoshima t, et al. dyskeratotic degeneration of epidermal cells in pityriasis rosea: light and electron microscopic studies. british journal of dermatology 1982; 107:189. 6. bukhari i. pityriasis rosea with palmoplantar plaque lesions. dermatology online journal 2005; 11(1): 27. 7. baughn re, musher dm. secondary syphilitic lesions. clinical microbiology reviews 2005; 18(1): 205-216. 8. smith g, holman rp. the prozone phenomenon with syphilis and hiv-1 co-infection. southern medical journal 2004; 97(4): 379-382. 9. nwabudike lc. does pityriasis rosea koebnerise? our dermatology online 2013; 4(2): 189-190. 10. weiss g, shemer a, trau h. the koebner phenomenon: review of the literature. jeadv 2002; 16: 241-248 bms-986165, an oral, selective tyrosine kinase 2 (tyk2) inhibitor: evaluation of changes in laboratory parameters in response to treatment in a phase 2 trial in psoriasis patients kenneth gordon,1 kim papp,2 melinda gooderham,3 akimichi morita,4 peter foley,5 diamant thaçi,6 sudeep kundu,7 renata kisa,7 lan wei,7 subhashis banerjee7 1medical college of wisconsin, milwaukee, wi, usa; 2clinical research and probity medical research inc, waterloo, on, canada; 3skin centre for dermatology, queen’s university and probity medical research, peterborough, on, canada; 4nagoya city university graduate school of medical sciences, nagoya, japan; 5the university of melbourne, st vincent’s hospital melbourne & probity medical research, skin & cancer foundation inc, melbourne, vic, australia; 6research institute and comprehensive center for inflammation medicine, university of lübeck, lübeck, germany; 7bristol-myers squibb company, princeton, nj, usa conclusions • there were no consistent differences observed between placebo and bms-986165 treatment groups in any hematologic parameters, serum chemistry (hepatic, renal, or lipid) parameters, or serum ig isotype levels • in addition, there were no clear dose-dependent changes observed with bms-986165 for any of the laboratory parameters investigated • results of 4 large ongoing phase 3 trials of bms-986165 (nct03624127 [poetyk-pso-1], nct03611751 [poetyk-pso-2], nct04167462 [poetyk-pso-3], and nct03924427) and the longterm extension study (nct04036435) in patients with moderate to severe plaque psoriasis will provide long-term safety and laboratory data introduction • tyk2 activates intracellular signal transducer and activator of transcription (stat)-dependent signaling pathways of specific cytokines, including interleukin (il)-23, il-12, and type i interferons, that are involved in the pathogenesis of psoriasis and other immune-mediated disorders1–5 • bms-986165, an oral, selective tyk2 inhibitor with a unique mode of binding to the pseudokinase domain of the enzyme rather than the atp binding site of the active kinase domain targeted by other tyrosine kinase inhibitors, provides high functional selectivity for tyk22,6 • in a 12-week, phase 2 trial (nct02931838) in adults with moderate to severe plaque psoriasis, bms-986165 demonstrated a dose-dependent improvement in psoriasis area and severity index (pasi) 75 response and a favorable safety profile7 — at week 12, pasi 75 responses were highest (67–75%) at doses from 3 mg twice daily (bid) up to 12 mg once daily (qd) versus placebo (7%; p<0.001; primary endpoint) objective • the objective of this post hoc analysis of the phase 2 trial was to assess the effect of bms-986165 on laboratory parameters methods patient population and study design • the phase 2 trial included adult patients with plaque psoriasis for 6 months and a body mass index of 18–40 kg/m2, who were eligible for phototherapy or systemic therapy and had moderate to severe disease as defined by affected body surface area ≥10%, pasi score ≥12, and static physician’s global assessment score ≥37 • patients were randomized to 1 of 5 oral doses of bms-986165 (3 mg every other day, 3 mg qd, 3 mg bid, 6 mg bid, 12 mg qd) or placebo7 • the treatment period was 12 weeks, with an additional 30-day off-treatment follow-up period for safety7 laboratory assessments • assessments of clinical laboratory parameters included hematologic parameters, c-reactive protein, metabolic parameters (creatinine, creatine phosphokinase [cpk], glucose, total cholesterol, high-density lipoprotein cholesterol [hdl-c], low-density lipoprotein cholesterol [ldl-c], and triglyceride levels), and immunoglobulin (ig) levels. other laboratory parameters were measured but are not presented here • mean (standard deviation [sd]), median (interquartile range), or median (range) absolute values for laboratory parameters are reported for the placebo group and the most clinically effective bms-986165 doses (ie, doses ≥3 mg bid). for this ad hoc analysis on the intention-to-treat cohort, data are shown for the 12-week treatment period results patient population • of the 267 patients who were randomized and received treatment in the phase 2 trial, 45 patients each received placebo, bms-986165 3 mg bid, or bms-986165 6 mg bid, and 44 received bms-986165 12 mg qd and were included in this analysis • patient demographics and baseline disease characteristics were generally similar across treatment groups7 laboratory parameters • hematologic parameters, including numbers of lymphocytes and neutrophils, platelet count, and hemoglobin levels, remained within normal ranges for placebo and bms-986165-treated patients over 12 weeks of treatment (figure 1) • other hematologic parameters assessed, including numbers of erythrocytes, leukocytes, and natural killer cells, were also within normal ranges (data not shown) figure 1. hematologic parameters at baseline and on treatment for all randomized and treated patients who received bms-986165 3 mg bid, 6 mg bid, or 12 mg qd or placebo m e an ( sd ) ly m p h o cy te n u m b e r, 1 0 3 c e ll s/ µl week 3 2 1 0 0 2 4 6 8 10 12 week 0 2 4 6 8 10 12 week 0 2 4 6 8 10 12 week 0 2 4 6 8 10 12 a m e an ( sd ) n e u tr o p h il n u m b e r, 1 0 3 c e ll s/ µl 10 4 2 0 b m e an ( sd ) h e m o gl o b in , g/ d l 18 4 2 0 c m e an ( sd ) p la te le t co u n t, 1 0 9 c e ll s/ l 350 100 50 0 d 8 6 8 6 12 10 16 14 200 150 300 250 lymphocyte number neutrophil number hemoglobin platelet count placebo (n=45) bms-986165 12 mg qd (n=44)bms-986165 6 mg bid (n=45)bms-986165 3 mg bid (n=45) data shown are for the 12-week treatment period. bid=twice daily; qd=every day; sd=standard deviation. • serum levels of c-reactive protein, creatinine, glucose, total cholesterol, hdl-c, and triglycerides remained within normal ranges during the 12-week trial period (table 1; figure 2). for patients with ldl-c values available, no increase was observed over 12 weeks of treatment (data not shown) • increases in cpk observed at 12 weeks in the placebo and bms-986165 groups were asymptomatic, mostly grade 1 or 2, and were observed in 12/44 (27%) patients who received placebo and 57/221 (26%) who received bms-986165 table 1. c-reactive protein, creatinine, and glucose levels at baseline and on treatment for all randomized and treated patients who received bms-986165 3 mg bid, 6 mg bid, or 12 mg qd or placebo bms-986165 absolute values placebo (n=45) 3 mg bid (n=45) 6 mg bid (n=45) 12 mg qd (n=44) c-reactive protein, mg/l baseline 3.863 (3.9629), n=45 4.344 (6.3423), n=45 3.397 (5.0866), n=44 3.159 (3.5864), n=41 week 4 3.128 (2.8095), n=44 3.623 (5.1206), n=42 4.413 (6.2391), n=39 3.517 (3.8205), n=44 week 12 4.046 (3.4668), n=31 4.910 (8.1941), n=43 2.638 (3.2964), n=39 3.426 (5.2116), n=41 creatinine, mg/dl baseline 0.846 (0.1535), n=45 0.849 (0.1957), n=45 0.797 (0.1400), n=45 0.778 (0.1503), n=44 week 4 0.858 (0.1443), n=44 0.845 (0.1790), n=42 0.784 (0.1371), n=39 0.801 (0.1515), n=44 week 12 0.808 (0.1210), n=32 0.843 (0.1788), n=43 0.794 (0.1382), n=39 0.788 (0.1553), n=41 glucose, mg/dl baseline 96.3 (21.03), n=45 99.3 (44.34), n=45 115.2 (79.93), n=45 98.3 (26.09), n=44 week 12 96.5 (16.14), n=31 100.0 (38.47), n=43 109.1 (51.36), n=39 100.8 (27.12), n=41 data are means (sd). data shown are for the 12-week treatment period. bid=twice daily; qd=every day; sd=standard deviation. 2020 pa & np fall clinical dermatology conference, november 13–15, 2020, orlando, florida copies of this poster obtained through quick response (qr) code are for personal use only and may not be reproduced without written permission from the authors of this poster. references 1. watford wt et al. immunol rev. 2004;202:139-156. 2. tokarski js et al. j biol chem. 2015;290:11061-11074. 3. volpe e et al. nat immunol. 2008;9:650-657. 4. geremia a et al. j exp med. 2011;208:1127-1133. 5. tucci m et al. clin exp immunol. 2008;154:247-254. 6. gillooly k et al. arthritis rheumatol. 2016;68(suppl10):abstract 11l. 7. papp k et al. n engl j med. 2018;379:1313-1321. 8. common terminology criteria for adverse events (ctcae) version 5.0. november 27, 2017. available at: https://ctep.cancer.gov/ protocoldevelopment/electronic_applications/docs/ctcae_v5_quick reference_5x7.pdf (accessed january 20, 2020). acknowledgments • this work was sponsored by bristol-myers squibb company. professional medical writing and editorial assistance was provided by catriona mckay, phd, and creative assistance during layout was provided by peloton advantage, llc, an open health company, parsippany, nj; both were funded by bristol-myers squibb company. relationships and activities • kg: grant support and consulting fees: abbvie, boehringer ingelheim, bristol-myers squibb, celgene, eli lilly, janssen, novartis, ucb; consulting fees: amgen, almirall, dermira, leo pharma, pfizer, sun pharma. • kp: speakers bureau: abbvie, amgen, astellas, celgene, eli lilly, galderma, janssen, kyowa hakko kirin, leo, merck sharp & dohme, novartis, pfizer, valeant; grant/research support: abbvie, akros, allergan, amgen, anacor, arcutis, astrazeneca, baxalta, boehringer ingelheim, bristolmyers squibb, celgene, coherus, dermira, dow pharma, eli lilly, galderma, genentech, glaxosmithkline, janssen, kyowa hakko kirin, leo, medimmune, meiji seika pharma, merck serono, novartis, pfizer, regeneron, roche, sanofi-aventis/genzyme, takeda, ucb, valeant; consultant: abbvie, akros, amgen, arcutis, astellas, astrazeneca, baxalta, baxter, boehringer ingelheim, bristol-myers squibb, canfite, celgene, coherus, dermira, dow pharma, eli lilly, forward pharma, galderma, genentech, janssen, kyowa hakko kirin, leo, meiji seika pharma, merck sharp & dohme, merck serono, mitsubishi pharma, novartis, pfizer, regeneron, roche, sanofi-aventis/genzyme, takeda, ucb, valeant; honoraria: abbvie, akros, amgen, baxter, boehringer ingelheim, celgene, coherus, eli lilly, forward pharma, galderma, glaxosmithkline, janssen, kyowa hakko kirin, merck sharp & dohme, merck serono, novartis, pfizer, takeda, ucb, valeant; scientific officer/steering committee/advisory board: abbvie, akros, amgen, anacor, astellas, baxter, boehringer ingelheim, bristol-myers squibb, celgene, dow pharma, eli lilly, galderma, janssen, kyowa hakko kirin, merck sharp & dohme, merck serono, novartis, pfizer, regeneron, sanofi-aventis/genzyme, valeant. • mg: speakers bureau, consultant, investigator/advisor: abbvie, akros, amgen, arcutis, boehringer ingelheim, bristol-myers squibb, celgene, dermira, eli lilly, galderma, glaxosmithkline, incyte, janssen, kyowa hakko kirin, leo pharma, merck, medimmune, novartis, pfizer, regeneron, roche, sanofi genzyme, takeda, ucb, valeant. • am: grant/research support, consultant, speakers bureau: abbvie, eli lilly, janssen, kyowa hakko kirin, leo pharma, maruho, mitsubishi-tanabe, novartis. • pf: speakers bureau, consultant, investigator, advisor, travel grants: 3m/inova/valeant, abbott/abbvie, amgen, biogen idec, boehringer ingelheim, bristol-myers squibb, celgene, celtaxsys, cutanea, dermira, eli lilly, galderma, glaxosmithkline/stiefel, janssen, leo/peplin, novartis, regeneron, sanofi genzyme, schering-plough/merck sharp & dohme, sun pharma, ucb, wyeth/pfizer. • dt: research support/principal investigator (clinical trials): abbvie, almirall, amgen, biogen idec, boehringer ingelheim, celgene, chugai, dermira, ds-pharma, eli lilly, galderma, gsk, janssen-cilag, leo, msd, novartis, pfizer, regeneron, roche, sandoz-hexal, sanofi, ucb; consultant: abbvie, almirall, celgene, dignity, galapagos, leo pharma, maruho, mitsubishi, novartis, pfizer, xenoport; lectures: abbvie, almirall, amgen, ds-pharma, janssen, leo pharma, msd, novartis, pfizer, la roche-posay, sandoz-hexal, sanofi, target-solution, ucb; scientific advisory board: abbvie, amgen, celgene, ds-pharma, eli lilly, galapagos, janssen-cilag, leo pharma, morphosis, msd, novartis, pfizer, sandoz, sanofi, ucb. • sk, rk, lw, sb: employees and shareholders of bristol-myers squibb company. to request a copy of this poster: scan qr code via a barcode reader application scientific content on demand qr codes are valid for 30 days after the congress date. figure 2. total cholesterol, hdl-c, triglyceride, and cpk levels at baseline and on treatment for all randomized and treated patients who received bms-986165 3 mg bid, 6 mg bid, or 12 mg qd or placebo baseline week 12 baseline week 12 m e an ( sd ) to ta l ch o le st e ro l, m g/ d l 250 200 100 150 50 0 a m e an ( sd ) h d lc , m g/ d l 70 20 10 0 b m e an ( sd ) tr ig ly ce ri d e s, m g/ d l 400 100 50 0 c m e an ( sd ) c p k , u /l 600 100 0 -100 20 4 6 week 8 10 12 d 50 30 60 40 200 150 300 250 350 300 200 500 400 total cholesterol hdl-c triglycerides cpk placebo (n=45) bms-986165 3 mg bid (n=45) bms-986165 6 mg bid (n=45) bms-986165 12 mg qd (n=44) placebo (n=45) bms-986165 3 mg bid (n=45) bms-986165 6 mg bid (n=45) bms-986165 12 mg qd (n=44) placebo (n=45) bms-986165 3 mg bid (n=45) bms-986165 6 mg bid (n=45) bms-986165 12 mg qd (n=44) baseline week 12 placebo (n=45) bms-986165 12 mg qd (n=44) bms-986165 6 mg bid (n=45) bms-986165 3 mg bid (n=45) data shown are for the 12-week treatment period. protocol-defined ulns for cpk were 180 u/l for females and 200 u/l for males. ctcae elevations in cpk are defined as: grade 1, >uln to 2.5 x uln; grade 2, >2.5 x uln to 5 x uln; grade 3, >5 x uln to 10 x uln; grade 4, >10 x uln.8 bid=twice daily; cpk=creatine phosphokinase; ctcae=common terminology criteria for adverse events; hdl-c=high-density lipoprotein cholesterol; qd=every day; sd=standard deviation; uln=upper limit of normal. • changes in cpk levels were not dose-dependent and there were no events resulting in discontinuation from the trial • serum levels of ige, iga, igm, and igg also stayed within normal ranges (figure 3) figure 3. immunoglobulin levels at baseline and on treatment for all randomized and treated patients who received bms-986165 3 mg bid, 6 mg bid, or 12 mg qd or placebo placebo (n=45) bms-986165 12 mg qd (n=44)bms-986165 6 mg bid (n=45)bms-986165 3 mg bid (n=45) m e d ia n ( iq r ) ig e , ku /l weekweek 0 2 4 6 8 10 12 d m e d ia n ( iq r ) ig a , m g/ l 0 2 4 6 8 10 12 c m e d ia n ( iq r ) ig m , m g/ l week 1500 0 0 2 4 6 8 10 12 b m e d ia n ( ra n ge ) ig g , m g/ d l week 3000 1000 500 0 0 2 4 6 8 10 12 a 500 10002000 1500 2500 igeiga igmigg 350 100 50 0 200 150 300 250 5000 1000 500 0 2000 1500 3000 3500 4000 4500 2500 data are medians (iqr) or medians (range). medians rather than mean data are shown due to skewing of data at the individual patient level. data shown are for the 12-week treatment period. bid=twice daily; ig=immunoglobulin; iqr=interquartile range; qd=every day; sd=standard deviation. http://www.globalbmsmedinfo.com introduction • the development of upper facial lines can negatively influence selfperception and may have adverse psychological impacts1-3 • subject satisfaction with aesthetic treatment reflects successful treatment outcomes, which consequently may be associated with improved selfesteem and body image1,2 • onabotulinumtoxina has been used effectively and safely to treat facial lines since the early 1990s4,5 • when treating forehead lines (fhl), concurrent treatment of glabellar lines (gl) is recommended to reduce the risk of eyebrow ptosis by maintaining a balance between eyebrow elevator muscles (primarily the frontalis muscle) and depressor muscles (including the procerus and corrugator muscles making up the glabellar complex)6 • the safety and efficacy of onabotulinumtoxina for treating fhl with 20 u to the frontalis muscle and 20 u to the glabellar complex was evaluated in a 12-month, phase 3 study7 ─ the primary endpoint—proportion of subjects achieving ≥2-grade improvement from baseline on day 30 in investigator and subject facial wrinkle scale with photonumeric guide (fws) scores of fhl severity at maximum eyebrow elevation—was met (61.4% with onabotulinumtoxina vs 0% with placebo; p<0.0001) objective • to present results from a 12-month, phase 3 study on the effects of onabotulinumtoxina on patient-reported satisfaction and to assess impacts of treatment methods patients • neurotoxin-naive males and females aged ≥18 years with both: ─ moderate to severe fhl at maximum eyebrow elevation (as assessed by both investigator and subject using the fws on study day 1, before treatment) ─ moderate to severe gl at maximum frown (as assessed by the investigator using the fws on study day 1, before treatment) study design • this 12-month, phase 3 study was conducted at 9 sites in the united states, 5 in canada, and 2 in europe (ireland) from october 2014 to april 2016 • the study comprised a 6-month double-blind, placebo-controlled, parallelgroup treatment period (days 1–180) followed by a 6-month open-label treatment period (days 180–360) (figure 1) • eligible subjects were randomized (3:1) to receive a single treatment consisting of onabotulinumtoxina 40 u (20 u in fhl and 20 u in gl) or placebo administered at 10 injection sites (figure 2) ─ onabotulinumtoxina 4u or placebo was given in 0.1 ml at each injection site • following the double-blind period, subjects could receive up to 2 open-label treatments with onabotulinumtoxina using the same 10 injection sites, with ≥84 days between treatment cycles • follow-up assessments were made at weeks 1 and 2 after each study treatment; all subjects also had follow-up visits every 30 days from study day 30 through day 360 figure 1. study design w1 w2 d30 d60 d90 d120 d150 d180 d210 d240 d270 d300 d330 d360 screening and randomization (3:1) period 1–double-blind treatment period 2–open-label treatment 40 u (20 u fhl + 20 u gl); n=300 40 u (20 u fhl + 20 u gl); n=400 study exit pbo (pbo fhl + pbo gl); n=100 screening, randomization, and treatment follow-up visit follow-up/criteria-based treatment visit d, day; fhl, forehead lines; gl, glabellar lines; pbo, placebo; w, week. figure 2. injection sites for onabotulinumtoxina treatment of fhl and gl forehead glabellar patient-reported outcome (pro) measures • subjects completed the facial line satisfaction questionnaire (flsq) and the 11-item facial line outcomes questionnaire (flo-11) at baseline, on days 7, 14, and 30, then every 30 days through day 360 • both pro instruments were developed, validated, and implemented in accordance with us food and drug administration guidance8,9 • the flsq (comprising 11 questions at baseline and 13 questions at follow-up) was designed to assess treatment satisfaction and appearancerelated impacts associated with fhl and gl from the subject’s perspective ─ flsq item 5 assesses subjects’ satisfaction with treatment of their facial lines ─ the impact domain measures appearance-related and emotional impacts of treatment, including appearance-related age, anger, tiredness, emotional unhappiness, and negative self-esteem • the flo-11 assesses psychological and appearance-related impacts associated with fhl and gl from the subjects’ perspective ─ item 4 evaluates whether subjects feel that they look older than their actual age statistical analysis • flsq item 5 and impact domain and flo-11 item 4 were included as key secondary efficacy endpoints as they reflect each subject’s perception of treatment effects and drive retreatment decisions ─ proportion of subjects mostly or very satisfied on flsq item 5 (primary time point: day 60) ─ proportion of responders on flsq impact domain, defined by ≥20-point improvement from baseline (primary time point: day 30) ─ proportion of responders on flo-11 item 4, defined by a ≥3-point improvement from baseline (primary time point: day 30) • these pros were evaluated in the intent-to-treat (itt) population, comprising all randomized subjects • between-group comparisons were conducted using the cochran-mantelhaenszel test, stratified by study site, with statistical significance achieved at p≤0.05 results subjects • the itt population comprised 391 subjects, including 290 in the onabotulinumtoxina group and 101 in the placebo group • the majority of subjects completed the study (n=333; 85.2%); discontinuations were mostly for personal reasons (n=39; 10.0%) or being lost to follow-up (n=15; 3.8%) ─ overall, 349 subjects (89.3%) received a second treatment cycle and 225 subjects (57.5%) received a third treatment cycle during the open-label period • demographics and baseline characteristics were similar between treatment groups (table 1) table 1. subject demographics and baseline characteristics (itt population) parameter onabotulinumtoxina (n=290) placebo (n=101) age, mean, years 44.5 42.4 range 18–77 22–64 female, n (%) 249 (85.9) 87 (86.1) caucasian, n (%) 260 (89.7) 87 (86.1) fhl severity at maximum eyebrow elevation, subject fws rating, n (%) moderate 138 (47.6) 48 (47.5) severe 152 (52.4) 53 (52.5) gl severity at maximum frown, investigator fws rating,* n (%) moderate 85 (29.3) 39 (38.6) severe 205 (70.7) 61 (60.4) flo-11 item 4 score,† mean (range) 5.9 (0–10) 5.6 (0–10) flsq impact domain score,‡ mean (range) 55.3 (0–100) 52.0 (0–100) *one subject in the placebo group had a rating of mild. †flo-11 item 4 scored on a scale from 0 (“not at all”) to 10 (“very much”). ‡ flsq impact domain scored from 0–100, with higher scores indicating facial lines have greater negative impact on the subject. fhl, forehead lines; flo-11, 11-item facial line outcomes questionnaire; flsq, facial line satisfaction questionnaire; fws, facial wrinkle scale; gl, glabellar lines; itt, intent-to-treat. flsq item 5 • the proportion of subjects who were mostly or very satisfied with study treatment was significantly greater with onabotulinumtoxina than placebo on day 30 (88.9% vs 3.0%; p<0.0001) and at the primary time point for this measure on day 60 (90.3% vs 1.0%; p<0.0001) • subject satisfaction with treatment remained significantly higher with onabotulinumtoxina than placebo at all time points through the end of the double-blind treatment period (ie, day 180; p<0.0001) (figure 3) • during the open-label period, subject satisfaction was maintained with repeated onabotulinumtoxina treatment, including in subjects initially allocated to placebo figure 3. subjects mostly or very satisfied on flsq item 5 over the 12-month study 0 10 20 30 40 50 60 70 80 90 100 day 7 day 14 day 30 day 60 day 90 day 120 day 150 day 180 m o s t ly s a t is fi e d o r v e r y s a t is f ie d ( % ) visit day onabotulinumtoxina (n=289) placebo (n=99, cycle 1) → onabotulinumtoxina period 1 period 2 * * * * * * * * day 7 day 14 day 30 day 60 day 90 day 7 day 14 day 30 day 60 day 90 cycle 3: open-labelcycle 2: open-labelcycle 1: double-blind *p<0.0001 for onabotulinumtoxina vs placebo. flsq impact domain • the responder rate on the flsq impact domain was significantly greater with onabotulinumtoxina than placebo on day 30 (73.9% vs 18.9%; p<0.0001) • the flsq impact domain responder rate remained significantly higher with onabotulinumtoxina than placebo at all time points through day 180 (p≤0.0007) (figure 4) • during the open-label treatment period, flsq impact domain responder rates were generally maintained with repeated onabotulinumtoxina treatment figure 4. responders achieving ≥20-point improvement from baseline on flsq impact domain over the 12-month study (subjects with baseline scores ≥20) r e s p o n d e r s o n f l s q i m p a c t d o m a in ( % ) visit day onabotulinumtoxina (n=268) placebo (n=9 , cycle 1) → onabotulinumtoxina period 1 period 2 * * * * * * * † 0 10 20 30 40 50 60 70 80 90 100 day 7 day 14 day 30 day 60 day 90 day 120 day 150 day 180 day 7 day 14 day 30 day 60 day 90 day 7 day 14 day 30 day 60 day 90 cycle 3: open-labelcycle 2: open-labelcycle 1: double-blind *p<0.0001; †p=0.0007 for both onabotulinumtoxina groups vs placebo. flo-11 item 4 • the responder rate on the flo-11 item 4 (looking older than actual age) was significantly greater with onabotulinumtoxina than placebo on day 30 (77.2% vs 11.2%; p<0.0001) • the flo-11 item 4 responder rate remained significantly higher with onabotulinumtoxina than placebo at all time points through day 180 (p≤0.0002) (figure 5) • like the other pro measures, the flo-11 responder rate was generally maintained with repeated onabotulinumtoxina treatment during the open-label period figure 5. responders achieving ≥3-point improvement from baseline on flo-11 item 4 over the 12-month study (subjects with baseline score ≥3) r e s p o n d e r s o n f l o 1 1 i t e m 4 ( % ) visit day onabotulinumtoxina (n=246) placebo (n= 9, cycle 1) → onabotulinumtoxina 0 10 20 30 40 50 60 70 80 90 100 day 7 day 14 day 30 day 60 day 90 day 120 day 150 day 180 day 7 day 14 day 30 day 60 day 90 day 7 day 14 day 30 day 60 day 90 period 1 period 2 * * * * * * * † cycle 3: open-labelcycle 2: open-labelcycle 1: double-blind *p<0.0001; †p=0.0002 for onabotulinumtoxina vs placebo. conclusions • subjects were highly satisfied with onabotulinumtoxina treatment of fhl and gl, and reported significant improvements in appearance-related and emotional impacts of their facial lines • these pro improvements were sustained for ≥6 months after a single treatment cycle and, thereafter, were maintained with repeated onabotulinumtoxina treatment references 1. finn cj, et al. dermatol surg. 2003;29(5):450-5. 2. cox se, finn jc. int ophthalmol clin. 2005;45(3):13-24. 3. gupta ma, gilchrest ba. dermatol clin. 2005;23(4):643-8. 4. carruthers jd, carruthers ja. j dermatol surg oncol. 1992;18(1):17-21. 5. carruthers j, et al. dermatol surg. 2015;41(6):702-11. 6. lorenc zp, et al. aesthet surg j. 2013;33(1 suppl):35s-40s. 7. fagien s, et al. presented at: international master course on aging sciences; february 1-3, 2017; paris, france. 8. pompilus f, et al. j cosmet dermatol. 2015;14(4):274-85. 9. yaworsky a, et al. j cosmet dermatol. 2014;13(4):297-306. acknowledgments this study was sponsored by allergan plc, dublin, ireland. medical writing and editorial assistance was provided to the authors by peloton advantage, parsippany, nj, usa, and was funded by allergan plc. all authors met the icmje authorship criteria. neither honoraria nor other form of payments were made for authorship. financial disclosures s dayan has received research support or speaking/consultant fees from allergan plc, galderma, merz aesthetics, and valeant. p ogilvie serves as an investigator for allergan plc. az rivkin serves as a consultant and investigator for allergan plc and merz aesthetics. sg yoelin serves as a consultant and investigator for allergan plc. jk garcia is an employee of allergan plc and may own stock/options in the company. il ferrusi was an employee of allergan plc at the time of the study. onabotulinumtoxina for treatment of moderate to severe horizontal frontalis lines and glabellar lines from the subject’s perspective: patient-reported satisfaction and impact outcomes from a phase 3 double-blind study steven dayan, md1; patricia ogilvie, md, phd2; alexander z. rivkin, md3; steven g. yoelin, md4; julie k. garcia, phd5; ilia l. ferrusi, phd5 1denova research, chicago, il; 2skinconcept, munich, germany; 3david geffen school of medicine, ucla, los angeles, ca; 4medical associates inc., newport beach, ca; 5allergan plc, irvine, ca scan to obtain pdf of poster to obtain a pdf of this poster: scan the qr code or visit www.allergancongressposters.com/935984 charges may apply. no personal information is stored. to view a video of the moa of botox-c, scan the qr code, then click on the “narrated poster” button. when prompted, enter the password botoxmoa123. note that the password is case sensitive. enter a valid e-mail to send this qr code or click to download. please ensure that qrcode@allergancongressposters.com has been added to your safe senders list or spam filter. fall clinical dermatology conference, las vegas, october 12-15, 2017 fc17posterallergandayanonabotulinumtoxinahorizontalfrontalislines.pdf microsoft word pv to pf.doc skin 37 brief articles a rare transition from pemphigus vulgaris to pemphigus foliaceus following rituximab therapy confirmed by antidesmoglein elisa samuel p. haslam ba,a katelyn f. woolridge md,b michael g. wilkerson mdb aschool of medicine, bdepartment of dermatology, university of texas medical branch, galveston, tx abstract pemphigus defines a group of blistering diseases characterized by autoimmunity against intraepidermal adhesion proteins and subsequent flaccid blister formation, two major subtypes of which are pemphigus foliaceus (pf) and pemphigus vulgaris (pv). of these, pf is typically more benign and characterized by igg autoantibodies against desmoglein-1 (dsg-1) with exclusive cutaneous involvement. in contrast, pv is typically more severe and characterized by igg autoantibodies against desmoglein-3 (dsg-3) in the mucosal predominant form and against both dsg-3 and dsg-1 in the mucocutaneous form1. july 2017 volume i issue i copyright 2017 the national society for cutaneous medicine the phenotypic expression of pemphigus subtypes is mediated by differences in desmoglein (dsg) autoantibody profiles, a concept that is demonstrated in rare cases of transition between pemphigus subtypes. diagnosis of transition is made on the basis of changes in classic phenotypic expression in conjugation with changes in immunofluorescence and/or antidesmoglein elisa. we report a 54-year-old male with a history of severe mucocutaenous pemphigus vulgaris (pv) brought into remission by treatment with systemic steroids and adjuvant rituximab infusions who re-presented approximately 1 year following steroid discontinuation with new crusted erosions covering the upper trunk and proximal extremities and notable absence of mucosal involvement. antidesmoglein elisa profile revealed an isolated rise in dsg-1 antibodies. previous antidesmoglein elisa profiles showed dual elevation in both dsg-1 and dsg-3 antibodies during active pv and absence of both dsg-1 and dsg-3 during disease remission. the current case describes a rare transition from pv to pemphigus foliaceus (pf) following rituximab therapy as suspected clinically by classic phenotypic expression and confirmed serologically by antidesmoglein elisa. this is only the second reported case of pemphigus transition following rituximab adjuvant therapy, and there are less than thirty cases of pv to pf transition reported in the literature. there is currently not a satisfactory explanation for the autoantibody shifting that is observed in transition between pemphigus types. abstract introduction skin 38 the phenotypic expression of pemphigus subtypes is mediated by differences in desmoglein autoantibody profiles2. this concept is demonstrated in rare cases of transition between pemphigus subtypes. diagnosis of transition is made on the basis of changes in classic phenotypic expression in conjugation with changes in immunofluorescence and/or antidesmoglein elisa3-7. in this report, we describe a rare case of transition from pv to pf following rituximab therapy confirmed serologically by antidesmoglein elisa. we report a 54-year-old male with a history of severe mucocutaneous pv brought into remission by treatment with systemic steroids and adjuvant rituximab infusions who re-presented with a new cutaneous eruption approximately 1 year following steroid discontinuation. physical examination revealed crusted erosions covering the upper trunk and proximal extremities with notable absence of mucosal involvement, consistent with the pf phenotype (figures 1 & 2). antidesmoglein elisa profile revealed an isolated rise in dsg-1 antibodies, confirming the suspected diagnosis of pf. previous antidesmoglein elisa profiles showed dual elevation in both dsg-1 and dsg-3 antibodies during active pv and absence of both dsg-1 and dsg-3 during disease remission (figure 3). the patient was stabilized by dermatology with topical clobetasol and oral doxycycline and underwent a complete four-infusion course of rituximab under the supervision of oncology, but was ultimately lost to follow up. case description july 2017 volume i issue i figures figures 1 & 2: scattered crusted erosions covering trunk and proximal upper extremities with no mucosal involvement, suggestive of pemphigus foliaceus. copyright 2017 the national society for cutaneous medicine skin july 2017 volume i issue i copyright 2017 the national society for cutaneous medicine 39 the current case describes a rare transition from pv to pf following rituximab therapy as suspected clinically by classic phenotypic expression and confirmed serologically by antidesmoglein elisa. the case supports the concept that differences in desmoglein autoantibody profiles mediate phenotypic expression of pemphigus subtypes. the patient displayed the mucocutaneous pv phenotype when both dsg-1 and dsg-3 autoantibodies were expressed, while he displayed the pf phenotype when only the dsg-1 autoantibody was present. the findings in the current case are consistent with the majority of prior case reports which have found dramatic changes in dsg-1 and dsg-3 autoantibody levels upon transition between pemphigus types3-7. the occurrence of transition between pemphigus subtypes in the literature is infrequent, with less than 30 cases identified of pv to pf transition and even fewer cases of pf to pv transition3-7. interestingly, the current case is only the second reported case of pemphigus transition following rituximab adjuvant therapy6. there is currently not a satisfactory explanation for autoantibody shifting involved in transition between pemphigus types. one proposed explanation is ‘epitope spreading’ in which autoreactive immune cells recognize epitopes on antigens that become exposed by prior autoantibody damage. this mechanism would theoretically support antigenicity gain involed in transition from pf to pv; however, it would not explain antigenticity loss involved in transition from pv to pf. furthermore, epitope spreading has been shown to be rare in pemphigus patients7. more research. is needed to elucidate the pathophysiology of transition between pemphigus subtypes. figure 3: rise and fall of desmoglein 1 & 3 auto-antibodies as a function of time and clinical disease appearance. note the present of dsg-1 & 3 autoantibodies during pemphigus vulgaris disease stage, with recurrence of only desmoglein-1 autoantibodies during pemphigus foliaceus. discussion skin july 2017 volume i issue i copyright 2017 the national society for cutaneous medicine 40 conflict of interest disclosures: none funding sources: none references: 1. kershenovich r, hodak e, mimouni d. diagnosis and classification of pemphigus and bulls pemphigoid. autoimmun rev 2014; 13: 477-81. 2. amagai m, tsunoda k, zillikens d et al. the clinical phenotype of pemphigus is defined by the anti desmoglein autoantibody profile. j am acad dermatol 1999;40: 167-170. 3. ng pp and thng st. three cases of transition from pemphigus vulgaris to pemphigus foliaceus confirmed by demoglein elisa. dermatology 2005; 210: 319-321. 4. park sg, chang jy, cho y-h et al. transition from pemphigus foliates to pemphigus vulgaris: case report with literature review. yonsei med j 2006; 47: 278-281. 5. awazawa r, yamamoto y, gushi m et al. case of pemphigus foliaceus that shifted into pemphigus vulgarism after adrenal tumor resection. j dermatol 2007;34: 549-555. 6. levy-sitbon c, reguiai z, durlach a et al. transition from pemphigus vulgaris to pemphigus foliaceus: a case report. ann dermatol verereol 2013; 140: 788-792. 7. ito t, moriuchi r, kikuchi k et al. rapid transition from pemphigus vulgaris to pemphigus foliaceus. j eur acad dermatol 2016; 30: 455-457. acknowledgements: medical writing support was provided by prescott medical communications group (chicago, il) with financial support from ortho dermatologics; ortho dermatologics is a division of bausch health us, llc • presented at winter clinical miami 2023 • february 17-20, 2023 • miami, fl synopsis � adherence to acne treatment is highest when the outcome is rapid and substantial1 � however, many acne medication regimens may take weeks or months to produce an improvement discernible by patients, leading to lower adherence2 � a three-pronged combination approach using once-daily application of an antibiotic, antibacterial, and retinoid may provide faster improvement than stand alone or dual combination products � the first triple-combination, fixed-dose acne topical in development, clindamycin phosphate 1.2%/benzoyl peroxide (bpo) 3.1%/adapalene 0.15% (idp-126) gel, was efficacious and safe in 3 clinical studies3,4 objective � to determine threshold lesion reductions for idp-126 gel and compare to its dyads and vehicle gel methods � a phase 2 (n=741; nct03170388) and two phase 3 (n=183; n=180; nct04214639; nct04214652), double-blind, 12-week studies enrolled participants aged ≥9 years with moderate-to-severe acne � participants were randomized to receive once-daily idp-126 or vehicle gel; the phase 2 study included three additional dyad gel randomization arms: bpo/adapalene; clindamycin phosphate/bpo; and clindamycin phosphate/adapalene � endpoints included least-squares mean percent change from baseline in inflammatory and noninflammatory lesion counts � the percentage of participants achieving ≥33%, ≥50%, and ≥75% thresholds in lesion reduction was evaluated results figure 1. one-third reduction in lesion counts: week 4 40% 0% 100% 80% 60% 20% 40% 0% 100% 80% 60% 20% n= 146 150 146 150 148 242 121 82.7% 65.9% 69.8% 68.6% 64.1% 78.9% 56.8% n= 146 150 146 150 148 242 121 68.9% 62.3% 49.8% 58.5% 41.3% 63.5% 50.1% p e rc e n ta g e o f p a rt ic ip a n ts in�ammatory lesions phase 2 study phase 3 pooled p e rc e n ta g e o f p a rt ic ip a n ts nonin�ammatory lesions phase 2 study phase 3 pooled early reductions in acne lesions by week 4 more participants achieved one-third reduction in lesions with idp-126 versus dyads and vehicle at week 4 idp-126 bpo/adap clin/bpo clin/adap veh dyads signi�cantly lower vs idp-126 dyad signi�cantly lower vs idp-126 participants with ≥33% reduction at week 4 *p<0.05, **p<0.01, ***p<0.001 active treatment vs vehicle. #p<0.05, ##p<0.01, ###p≤0.001 dyads vs idp-126. adap, adapalene; bpo, benzoyl peroxide; clin, clindamycin phosphate; veh, vehicle. figure 2. one-half reduction in lesion counts: weeks 4 –12 40% 0% 100% 80% 60% 20% 40% 0% 100% 80% 60% 20% phase 2 study phase 3 pooled 40% 0% 100% 80% 60% 20% 40% 0% 100% 80% 60% 20% phase 2 study phase 3 pooled p e rc e n ta g e o f p a rt ic ip a n ts in�ammatory lesions bl nonin�ammatory lesions bl early and sustained reductions in acne lesions more participants achieved one-half reduction in lesions with idp-126 versus dyads and vehicle as early as week 4, with signi�cant reduction maintained at weeks 8 and 12 88.7% 78.2% 77.4% 77.9% 55.9% 37.9% 56.0% 63.9% 86.5% 17.8% idp-126 gel (n=146) bpo/adap gel (n=150) clin/bpo gel (n=146) clin/adap gel (n=150) vehicle gel (n=148) idp-126 gel (n=242) vehicle gel (n=121) 79.1% 58.5% 36.0% p e rc e n ta g e o f p a rt ic ip a n ts bl bl 84.6% 68.3% 71.4% 70.5% 51.5% 32.5% 48.4% 54.0% 84.3% 15.5% idp-126 gel (n=146) bpo/adap gel (n=150) clin/bpo gel (n=146) clin/adap gel (n=150) vehicle gel (n=148) idp-126 gel (n=242) vehicle gel (n=121) 65.1% 44.4% 20.4% all dyads signi�cantly lower vs idp-126 at weeks 4, 8, and 12 all dyads signi�cantly lower vs idp-126 at weeks 8 and 12 participants with ≥50% reduction at all weeks week 2 week 4 week 8 week 12 week 2 week 4 week 8 week 12 week 2 week 4 week 8 week 12 week 2 week 4 week 8 week 12 *p<0.05, **p≤0.01, ***p≤0.001 active treatment vs vehicle. #p<0.05, ##p<0.01 dyads vs idp-126. adap, adapalene; bpo, benzoyl peroxide; clin, clindamycin phosphate; veh, vehicle. figure 3. three-fourths reductions in lesion counts: week 12 40% 0% 100% 80% 60% 20% 40% 0% 100% 80% 60% 20% n= 146 150 146 150 148 242 121 65.8% 51.2% 50.1% 49.9% 21.6% 68.1% 33.4% n= 146 150 146 150 148 242 121 53.2% 38.3% 36.9% 40.2% 18.9% 55.0% 24.8% p e rc e n ta g e o f p a rt ic ip a n ts in�ammatory lesions phase 2 study phase 3 pooled p e rc e n ta g e o f p a rt ic ip a n ts nonin�ammatory lesions phase 2 study phase 3 pooled substantial reductions in acne lesions by week 12 signi�cantly more participants achieved three-fourths reduction in lesions with idp-126 versus dyads and vehicle at week 12 idp-126 bpo/adap clin/bpo clin/adap veh dyads signi�cantly lower vs idp-126 dyads signi�cantly lower vs idp-126 participants with ≥75% reduction at week 12 ***p≤0.001 active treatment vs vehicle. #p<0.05, ##p≤0.01 dyads vs idp-126. adap, adapalene; bpo, benzoyl peroxide; clin, clindamycin phosphate; veh, vehicle. early and sustained reductions in moderate-to-severe acne with fixed-dose clindamycin phosphate 1.2%, benzoyl peroxide 3.1%, and adapalene 0.15% gel julie c harper, md1; leon h kircik, md2-4; michael gold, md5; adelaide a hebert, md6; jeffrey l sugarman, md, phd7; lawrence green, md8; linda stein gold, md9; hilary baldwin, md10; james q del rosso, do11-13; eric guenin, pharmd, phd, mph14 1dermatology & skin care center of birmingham, birmingham, al; 2icahn school of medicine at mount sinai, new york, ny; 3indiana university medical center, indianapolis, in; 4physicians skin care, pllc, dermresearch, pllc, and skin sciences, pllc, louisville, ky; 5tennessee clinical research center, nashville, tn; 6uthealth mcgovern medical school, houston; houston, tx; 7university of california, san francisco, ca; 8george washington university school of medicine, washington, dc; 9henry ford hospital, detroit, mi; 10the acne treatment and research center, brooklyn, ny; 11jdr dermatology research/thomas dermatology, las vegas, nv; 12advanced dermatology and cosmetic surgery, maitland, fl; 13touro university nevada, henderson, nv; 14ortho dermatologics, bridgewater, nj* *ortho dermatologics is a division of bausch health us, llc conclusions � therapeutic effects of idp-126 gel were rapid and sustained � lesion count reductions were greater with idp-126 versus its dyads and vehicle gel as early as week 4, with substantial reductions observed after 12 weeks of idp-126 treatment � this fast-acting feature of idp-126—coupled with its optimized efficacy, once a day application, and good tolerability—may positively impact treatment adherence references 1. sevimli dikicier b. j int med res. 2019;47(7):2987-2992. 2. tuchayi sm. patient prefer adherence. 2016;10:2091–2096. 3. stein gold l. am j clin dermatol. 2022;23(1):93-104. 4. stein gold l. j am acad dermatol. 2022;87(3):supp ab50. author disclosures julie harper has received honoraria from aclaris, almirall, biopharmx, cassiopea, cutanea, dermira, foamix, galderma, laroche-posay, ortho dermatologics, and sun. leon kircik has acted as an investigator, advisor, speaker, and consultant for ortho dermatologics. michael gold has acted as an investigator, advisor, speaker, and consultant for ortho dermatologics. adelaide a. hebert has received honoraria from galderma, leo pharma, amirall, cassiopea, ortho dermatologics, cutanea, ferrer, pfizer, demira. the uthealth mcgovern medical school had received research grants from cassiopea, demira, ortho dermatologics. jeffrey l sugarman is a consultant for ortho dermatologics, bausch health, regeneron, sanofi, verrica, and pfizer. lawrence green has served as investigator, consultant, or speaker for almirall, cassiopea, galderma, ortho dermatologics, sol gel, sun pharma, and vyne. linda stein gold has served as investigator/consultant or speaker for ortho dermatologics, leo pharma, dermavant, incyte, novartis, abbvie, pfizer, sun pharma, ucb, arcutis, and lilly. hilary baldwin has served as advisor, investigator, and on speakers’ bureaus for almirall, cassiopea, foamix, galderma, ortho dermatologics, sol gel, and sun pharma. james q. del rosso has served as a consultant, investigator, and/or speaker for ortho dermatologics, abbvie, amgen, arcutis, dermavant, epi heath, galderma, incyte, leo pharma, lilly, mc2 therapeutics, pfizer, sun pharma, and ucb. eric guenin is an employee of ortho dermatologics and may hold stock and/or stock options in its parent company. microsoft word september 2020 can 938 proof.docx skin september 2020 volume 4 issue 5 copyright 2020 the national society for cutaneous medicine 488 commentary & notes commentary in response: commentary on “avoiding the hazards of ultraviolet light in the adolescent population” alexander auchus1, robert t. brodell, md2, vinayak k. nahar md, ms, phd, frsph2,3, kimberley h.m. ward, md2 1department of psychology, school of arts and sciences, university of pennsylvania, philadelphia, pa 2department of dermatology, school of medicine, university of mississippi medical center, jackson, ms 3department of preventive medicine, school of medicine, university of mississippi medical center, jackson, ms we appreciate the opportunity to respond to the commentary by weisert and hinds on our recent publication “avoiding the hazards of ultraviolet light in the adolescent population.”1 weisert and hinds addressed the emerging evidence on effects of visible light on premature aging and proposed a need for utilizing a topical antioxidant serum in addition to daily sunscreen. we appreciate their interest in our work; however, our article discussed the “standard of care” in 2020 and there is risk in recommending approaches that are not yet proven and in diluting our simple message: wear a hat, use sunscreen, and sit under cover especially during mid-day. conflict of interest disclosures: robert brodell, m.d. discloses the following potential conflicts of interest: multicenter clinical trials: galderma laboratories, l.p. – principal investigator; novartis principal investigator; and, glaxo smith kline – principal investigator. editorial boards: american medical student research journal; practice update dermatology; practical dermatology; journal of the mississippi state medical society; skin: the journal of cutaneous medicine and, journal of the american academy of dermatology. there are no conflicts of interest related to employment, stock ownership, expert testimony, grants, patents filed, received, pending, or in preparation, or royalties. alexander auchus, vinayak k. nahar, and kimberly ward have no conflicts of interest. funding: none corresponding author: vinayak k. nahar, md, phd, ms, frsph department of dermatology school of medicine university of mississippi medical center 2500 north state street – l216 jackson, ms 39216 phone: 601-495-5876 fax: 601-984-1150 email: naharvinayak@gmail.com references: 1. auchus, a., brodell, r. t., nahar, v. k., & ward, k.h.m. (2020). avoiding the hazards of ultraviolet light in the adolescent population. skin the journal of cutaneous medicine, 4(3), 189-199. introduction calcipotriene plus betamethasone dipropionate (0.005%/0.064%) foam vs halobetasol propionate and tazarotene (0.01%/0.045%) lotion: matching-adjusted indirect comparison & us cost-per-responder analysis jashin j. wu, md1, jes b. hansen, phd2, dharm s. patel, phd2, nanna nyholm jensen, msc2, karen a. veverka, phd2, andrine r. swensen, ms, phd2 1dermatology research and education foundation, irvine, ca 2leo pharma, ballerup, dk & madison, nj acknowledgements references  fixed-combination topical treatments for plaque psoriasis provide treatment advantages via a dual mechanism of action. the combination of active pharmaceutical ingredients (api), skin penetration, bioavailability of apis, and formulation can impact clinical efficacy.  additionally, adherence is impacted by length of therapy and vehicle acceptability. in the absence of head-to-head trials, a comparison of relative effectiveness between fixedcombination topical treatments is pertinent.  calcipotriene and betamethasone dipropionate (0.005%/0.064%, cal/bd) foam is a fixed-combination, once-daily topical treatment of plaque psoriasis in patients 12 years of age and older.1  halobetasol propionate and tazarotene (0.01%/0.045%, hp/taz) lotion is a fixed-combination, once-daily topical treatment of plaque psoriasis in adults.2 study design  maic use individual patient data (ipd) from trials of one treatment to match baseline summary statistics reported from trials of another treatment to compare treatment outcomes across a balanced patient population.3  baseline characteristics for matching were selected based on clinical input and by forward selection using a logistic model, with the relevant end point (ie, treatment success) as the dependent variable and selection entry criteria, p<0.2.  available baseline variables for matching included disease severity (pga, bsa), quality of life, demographics, duration of psoriasis, body mass index, and history of topical treatment (table 1).  maic analysis was conducted between cal/bd foam and hp/taz lotion, number-needed-to-treat (nnt) was conducted between active treatment and respective vehicle, and associated pharmacoeconomic evaluation through us incremental cost per responder analysis (icpr). figure 1. methodology of maic analysis of cal/bd foam and hp/taz lotion  this analysis used an anchored maic to balance baseline characteristics of study populations in an indirect, comparative effectiveness evaluation of two fixedcombination topical treatments for plaque psoriasis.  evaluation demonstrates that cal/bd foam treatment has statistically greater difference in pga 0/1 response rates, a lower cost per pga 0/1 responder, and quicker treatment response than hp/taz lotion in adult patients with moderate-to-severe plaque psoriasis. table 2. anchored maic evaluating pga ‘treatment success’ response rates and nnt for cal/bd foam and hp/taz lotion.  after reweighting of patients and anchoring to vehicle effect, significantly more cal/bd foam patients demonstrated greater difference in treatment success relative to vehicle after 4 weeks than did hp/taz lotion patients after 8 weeks (51.4% vs 30.7%; treatment difference=20.7%; p<.001) (table 2)  the number needed to treat (nnt) relative to vehicle with cal/bd foam was also less than hp/taz lotion (1.9 vs 3.3). poster presented at the 17th annual winter clinical dermatology conference hawaii® puako, hi, january 17-22nd, 2020 figure 2. average cost per pga responder for cal/bd foam and hp/taz lotion based on the anchored maic analysis. this study was sponsored by leo pharma. table 3. economic evaluation of cal/bd foam for 4 weeks and hp/taz lotion for 8 weeks for treatment of moderate plaque psoriasis through a cost per pga ‘treatment success’ responder analysis. conduct an anchored matching-adjusted indirect comparison (maic) and incremental cost per responder (icpr) analysis using individual patient data from cal/bd foam studies and aggregate patient characteristics and outcomes from published efficacy assessments of hp/taz lotion in adult patients with moderate-to-severe plaque psoriasis. table 1. identification of cal/bd foam and hp/taz lotion trials for maic analysis  incremental cost per responder analysis was based on the fda prescribing information1,2 and anchored maic analysis using us wholesale acquisition cost (wac) drug pricing from june 2019 (analysource®).  cost per treatment period was calculated by multiplying the per gram drug wac with the average consumption of study drug over treatment period of 4 weeks and 8 weeks, respectively, assuming equal weekly consumption rates.  the estimated incremental cost per responder (icpr) was calculated by multiplying the nnt by the overall drug costs throughout the treatment period and corresponds to the additional cost to achieve 1 additional responder for each of the treatments vs vehicle (table 3).  the incremental cost per pga 0/1 responder relative to vehicle for cal/bd foam was $3988 and is 37% lower compared with hp/taz lotion ($6294) (figure 2).  observed (e.g. patient randomization) and unobserved (e.g. vehicle) cross-trial differences may not be accounted for in the analysis  comparative safety analyses and associated economic impact were not conducted.  wac prices do not reflect manufacturer rebates, are not reflective of actual spend, and are dated june 2019.  time to response difference between cal/bd foam (4 weeks)1 and hp/taz lotion (8 weeks)2.  imbalance in sample size exists due to applicable publications on comparator, and may not be fully addressed by methodology.  analyses based on clinical trials may not be generalizable to the real world.  additional head-to-head research should be conducted to confirm these comparative effectiveness findings. 1. enstilar® foam [package insert]. madison, nj: leo pharma inc. july 2019 2. duobrii™ lotion [package insert]. bridgewater, nj: bausch health americas, inc. april 2019 3. signorovitch, je, sikirica v, erder mh, et al. value in health. 2012;12:940-947. 4. leonardi c et al. j drugs dermatol. 2015;14(12):1468-1477; 5. paul c et al. j eur acad dermatol venereol. 2017;31(1):119-126; 6. koo j et al. j dermatol treat. 2016;27(2);120-127; 7. sugarman jl et al. j drugs dermatol. 31 jul 2018, 17(8):855-861 8. analysource®, dmd america; accessed june 2019) bmi, body mass index; bsa, body surface area; pasi, psoriasis area and severity index; dlqi, dermatology life quality index; iga, investigator’s global assessment; qd, once daily objective methods results limitations conclusions disclosures jjw has been an advisor with/without funding from leo pharma inc. jbh, dsp, nnj, kav, and ars are employees of leo pharma. potential matching variables pooled cal/bd foam studies pooled hp/taz lotion studies study design three multicenter, randomized, double-blind, controlled studies4-6 two multicenter, randomized, double-blind, vehicle-controlled phase 3 studies7 dosing qd (4 weeks) qd (8 weeks) treatment cal/bd foam foam vehicle all hp/taz lotion lotion vehicle all n 649 199 848 276 142 418 mean age (sd), y 52.0 (13.9) 48.0 (14.0) 51.0 (14.0) 50.0 (14.2) 51.0 (13.2) 50.3 (13.8) male, n (%) 417 (64.3) 108 (54.3) 525 (61.9) 175 (63.4) 97 (68.3) 272 (65.1) white/caucasian, n (%) 577 (88.9) 180 (90.5) 757 (89.3) 232 (84.1) 126 (88.7) 358 (85.6) mean bmi (sd), kg/m2 31.3 (7.3) 31.2 (7.9) 31.2 (7.4) mean bsa (sd), % 7.4 (6.3) 7.9 (6.8) 7.5 (6.4) 6.0 (2.9) 5.7 (2.5) 5.9 (2.8) mean duration of psoriasis (sd), y 17.1 (14.0) 15.8 (12.5) 16.8 (13.7) nr nr nr mean pasi (sd) score 7.2 (4.6) 7.5 (5.5) 7.3 (4.8) nr nr nr iga, n (%) mild moderate severe 126 (19.4) 465 (71.6) 58 (8.9) 38 (19.1) 140 (70.4) 21 (10.6) 164 (19.3) 605 (71.3) 79 (9.3) 237 (85.9) 39 (14.1) 119 (83.9) 23 (16.2) 356 (85.2) 62 (14.8) study selection  published clinical trials with sufficiently similar populations and outcomes to support indirect comparisons were identified for cal/bd foam and hp/taz lotion (figure 1).  comparative studies were excluded for the following reasons: the sample size included fewer than 40 patients (this exclusion was stipulated to preserve adequate statistical power); treatment efficacy was not measured, or time points of efficacy measurements were not specified; baseline characteristics were not reported; and the mean baseline psoriasis area and severity index (pasi) or body surface area (bsa) were greater than 15. pooled data treatment cal/bd foam (+vehicle)4-6 hp/taz lotion (+vehicle)7before re-weighting after re-weighting effective sample size, n 649 (+199) 586 276 (+142) baseline pga, % moderate severe 71.3% 9.3% 85.2% 14.8% 85.2% 14.8% bsa 7.5% 5.9% 5.9% male, n (%) ​​ 61.9% 65.1% 65.1% white/caucasian at baseline, % 89.3% 85.6% 85.6% active pga treatment success rate (95% ci) 48.5% (41.2%, 55.9%) 55.7% (52.3%, 59.1%) 40.6% (34.8%, 46.4%) vehicle pga treatment success rate (95% ci) 5.0% (4.4%, 5.7%) 4.3% (3.5%, 5.1%) 9.9% (5.0%, 14.8%) active vehicle difference in pga success rates (95% ci) 43.5% (36.5%, 50.5%) 51.4% (47.6%, 55.2%) 30.7% (23.1%, 38.3%) anchored maic difference in pga success rates between cal/bd foam & hp/taz lotion (95% ci; p-value) 20.7% (12.2%, 29.1%; p<.001) number needed to treat (nnt) relative to vehicle cal/bd foam vs hp/taz lotion 1.9 vs 3.3 pga, physicians’ global assessment; bsa, body surface area; maic, matching adjusted indirect comparison no units/pack grams per unit unit cost per pack (wac) [$]8 cost per gram treatment period [weeks] quantity used per treatment period anchored maic: pga 0/1 (4 vs. 8 weeks) icpr per pga 0/1 responder [$] cal/bd foam 1 60 gm $1050 $17.50 4 117.1 gm* 51.4% $3988 hp/taz lotion 1 100 gm $825 $8.25 8 234.2 gm** 30.7% $6294 data source prescribing information prescribing information analysource® (3rd party provider of us pricing information; june 2019) analysource® (3rd party provider of us pricing information; june 2019) anchored maic (pooled data from 3 cal/bd studies; 2 hp/taz studies) *pooled consumption from 3 cal/bd studies **assumes equal weekly consumption to cal/bd (data nr) anchored maic (pooled data from 3 cal/bd studies; 2 hp/taz studies) cost-per-responder  define inclusion and exclusion criteria  define search terms to identify comparator studies in the literature literature search for hp/taz lotion comparator studies  cal/bd foam randomized controlled trials  pooled analysis (3 trials) of cal/bd foam randomized controlled trials identify cal/bd foam trials available with ipd for analysis  identify comparator trials to perform indirect efficacy comparison  identify matching variable priorities between comparator aggregate data and ipd for cal/bd foam maic inputs: cal/bd foam vs hp/taz lotion  indirect effectiveness comparison (pga) between treatment options before and after re-weighting of matching variables maic analysis output $ $1,000 $2,000 $3,000 $4,000 $5,000 $6,000 $7,000 $8,000 c o st -p e r p g a 't re a tm e n t su c c e ss ' r e sp o n d e r $3988 $6294 δ 37% cal/bd foam hp/taz lotion slide number 1 acknowledgements: medical writing support was provided by prescott medical communications group (chicago, il) with financial support from ortho dermatologics; ortho dermatologics is a division of bausch health us, llc | presented at winter clinical dermatology conference 2020 • january 17-22, 2020 • kohala coast, hi synopsis ◾ acne is a common problem among asian adolescents and adults1 ◾ generally, asian skin is more pigmented than white people of european descent, and asians have a high risk of acne sequelae such as post-inflammatory hyperpigmentation1 ◾ the first tretinoin lotion 0.05% formulation was developed by utilizing novel polymeric emulsion technology to provide an alternative, lower-dose tretinoin option for patients who may be sensitive to the irritant effects of other tretinoin formulations2 ◾ tretinoin 0.05% lotion was efficacious and well tolerated in two phase 3 studies of participants ≥9 years of age with moderate-to-severe acne (nct02932306, nct02965456)3 objective ◾ to assess efficacy and safety of tretinoin 0.05% lotion in asian participants with moderate-tosevere acne and to place these data into context with the overall study population methods ◾ in two phase 3, double-blind, vehicle-controlled 12-week studies, eligible participants aged ≥9 years with moderate-to-severe acne were randomized (1:1) to receive once-daily tretinoin 0.05% lotion or vehicle • in these studies, cerave® hydrating cleanser and cerave® moisturizing lotion (l’oreal, ny) were provided as needed for optimal moisturization/cleaning of the skin ◾ data from these two studies were pooled and analyzed post hoc for asian participants and the total population ◾ efficacy assessments included reductions in noninflammatory/inflammatory lesion counts and treatment success, defined as percent of participants achieving ≥2-grade reduction in evaluator’s global severity score (egss) and a clear/almost clear score ◾ adverse events (aes) and cutaneous safety/tolerability were also assessed results participants ◾ a total of 1,640 participants were included in the pooled intent-to-treat analysis, of whom 69 were asian (mean age 20.9 years [range: 12–48 years]; 60.9% female) efficacy ◾ at week 12, least-squares mean percent reductions from baseline in inflammatory lesion counts were greater with tretinoin 0.05% lotion versus vehicle—slightly greater in magnitude than the overall population—but the difference was not significant in asian participants (figure 1a) ◾ noninflammatory lesion count reductions were significantly greater with tretinoin 0.05% lotion versus vehicle in asian participants and all participants (figure 1b) ◾ treatment success at week 12 was greater with tretinoin 0.05% lotion versus vehicle in asians and all participants, though this difference was not significant in asians (figure 2) novel tretinoin 0.05% lotion for the once-daily treatment of moderate-to-severe acne vulgaris in asians figure 2. percentage of asian and all participants achieving treatment successa at week 12 (itt population, pooled) 20% 25% 30% 27.2% 17.7%16.9% 9.3% 0 5% 10% 15% 35% asian participants all participants p e rc e n ta g e o f p a rt ic ip a n ts 36 33 819 821 tretinoin 0.05% lotion vehicle lotion n= ***p<0.001 vs vehicle. adefined as ≥2-grade reduction from baseline in evaluator’s global severity score with a final grade of 0 (clear) or 1 (almost clear). multiple imputation method used for missing values. itt, intent-to-treat. figure 3. cutaneous safety and tolerability in asian and all participants treated with tretinoin 0.05% lotion (safety population, pooled) 0 1 2 3 m e a n s co re baseline week 4 week 8 week 12 scaling (asian) erythema (asian) scaling (all) erythema (all) 0 1 2 3 baseline week 4 week 8 week 12 itching (asian) burning (asian) burning (all) stinging (all) 0 1 2 3 baseline week 4 week 8 week 12 hypopigmentation (asian) hyperpigmentation (asian) hypopigmentation (all) hyperpigmentation (all) stinging (asian) itching (all) no imputation for missing values. figure 1. mean percent reduction from baseline in inflammatory (a) and noninflammatory (b) lesion counts in asian and all participants (itt population, pooled) -22.0% -44.4% -58.6% -24.1% -35.0% -41.5% -70% -60% -50% -40% -30% -20% -10% 0% ls m e a n p e rc e n t c h a n g e f ro m b a se lin e asian participants tretinoin 0.05% lotion (n=36) vehicle lotion (n=33) baseline week 4 week 8 week 12 a. in�ammatory lesions -27.9% -40.7% -52.1% -24.7% -33.2% -41.0% -70% -60% -50% -40% -30% -20% -10% 0% ls m e a n p e rc e n t c h a n g e f ro m b a se lin e all participants tretinoin 0.05% lotion (n=819) vehicle lotion (n=821) baseline week 4 week 8 week 12 -24.5% -34.5% -51.4% -6.6% -9.4% -23.9% -70% -60% -50% -40% -30% -20% -10% 0% ls m e a n p e rc e n t c h a n g e f ro m b a se lin e asian participants tretinoin 0.05% lotion (n=36) vehicle lotion (n=33) baseline week 4 week 8 week 12 b. nonin�ammatory lesions -22.7% -34.9% -46.1% -15.8% -23.7% -29.9% -70% -60% -50% -40% -30% -20% -10% 0% ls m e a n p e rc e n t c h a n g e f ro m b a se lin e all participants tretinoin 0.05% lotion (n=819) vehicle lotion (n=821) baseline week 4 week 8 week 12 *p<0.05 vs vehicle; ***p<0.001 vs vehicle. multiple imputation method used for missing values. itt, intent-to-treat; ls, least squares. safety ◾ in tretinoin-treated participants, treatment-emergent aes (teaes) were reported in 14.7% of asian and 23.5% of all participants (table 1) • in asian participants, all teaes were mild or moderate and none were related to treatment ◾ slight transient increases occurred over the first 4-8 weeks in scaling, burning, and stinging (all and asian) and itching (asian); most scores were generally similar to baseline by week 12 (figure 3) • mild hyperpigmentation was reported at baseline for asian participants (mean score 0.7) and remained mild throughout the study (0.6-0.7) table 1. adverse events (safety population, pooled) asian participants all participants tretinoin 0.05% (n=34) vehicle (n=31) tretinoin 0.05% (n=767) vehicle (n=783) summary of aes, n (%) any ae 5 (14.7) 6 (19.4) 180 (23.5) 151 (19.3) any serious aea 0 0 7 (0.9) 4 (0.5) severity of aes, n (%) mild 3 (8.8) 5 (16.1) 105 (13.7) 95 (12.1) moderate 2 (5.9) 1 (3.2) 67 (8.7) 46 (5.9) severe 0 0 8 (1.0) 10 (1.3) relationship to study drug, n (%) relatedb 0 1 (3.2) 62 (8.1) 15 (1.9) unrelated 5 (14.7) 5 (16.1) 118 (15.4) 136 (17.4) ano serious aes were considered related to treatment. ball related treatment-emergent aes were classified as general disorders and administration site conditions. ae, adverse event. conclusions ◾ data pooled from two phase 3 studies showed that treatment with tretinoin 0.05% lotion provided statistically greater reductions in noninflammatory lesion counts versus vehicle in asian participants, similar to the overall study population ◾ the lack of statistical significance versus vehicle for inflammatory lesions and treatment success in asian participants may be due to the small number (n=69) in this analysis, as mean values for these efficacy assessments were similar to or greater than the overall study population ◾ tretinoin 0.05% lotion was well tolerated in asian and all participants, with mean cutaneous safety and tolerability ratings between none and mild, including hyperpigmentation references 1. see ja, et al. j dermatol. 2018;45(5):522-528. 2. kircik lh, et al. j drugs dermatol. 2019;18(4):s148-154. 3. tyring sk, et al. j drugs dermatol. 2018;17(10):1084-1091. author disclosures dr. george han has nothing to disclose. dr. april armstrong has served as a research investigator and/or consultant for abbvie, janssen, leo, novartis, ucb, ortho dermatologics, dermira, sanofi, regeneron, bms, dermavant, and modernizing medicine. dr. seemal desai has served as a research investigator and/or consultant for skinmedica, ortho dermatologics, galderma, pfizer, dermavant, almirall, dermira, and watson. dr. eric guenin is an employee of ortho dermatologics and may hold stock or stock options in its parent company. george han, md, phd1; april w armstrong, md, mph2; seemal r desai, md3,4; eric guenin, pharmd, phd, mph5 1icahn school of medicine at mount sinai, new york, ny; 2keck school of medicine at university of southern california, los angeles, ca; 3innovative dermatology, pa, plano, tx; 4the university of texas southwestern medical center, dallas, tx; 5ortho dermatologics*, bridgewater, nj *ortho dermatologics is a division of bausch health us, llc. skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 102 clinical management recommendations dermatologists’ management approach to sexually transmitted disease ted rosen, md1 1professor of dermatology, baylor college of medicine, houston, tx why is this subject important? there has been a massive resurgence of sexually transmitted diseases (std) in recent years. based upon public health reporting and epidemiologic models, the global incidence of stds exceeds one million new cases daily, along with a prevalence of 700 million individuals with genital herpes and external genital warts.1 in the united states, for example, more cases and higher rates of gonorrhea, syphilis and congenital lues have been reported for five years in a row (2014-2018).2 in europe, the incidence of syphilis, in particular, has dramatically increased in many countries.3 some of the consequence of std include acute morbidity, long term neurologic or cardiac disability, psychic distress, neonatal morbidity and even mortality, and infertility. is std relevant for dermatology? remember that our specialty was once called “dermatology and syphilology.” in modern times, both our key journals and our academic centers have de-emphasized stds, including syphilis, to reflect the evolving focus of dermatological practice.4 however, we are currently faced with a set of diseases associated with serious consequences that are simply refusing to disappear, and are even increasing worldwide at alarming rates. many of these disorders have major manifestations on the skin or may involve the hair and oral mucosa. who better than a dermatologist to recognize in high-risk constituencies, and others, that patchy non-scarring hair loss may represent syphilitic alopecia and that annular facial lesions may represent secondary syphilis?5 who is (or should be) most capable of distinguishing condyloma lata from condyloma accuminata? shouldn’t the dermatologist know how to differentiate between the various infectious and noninfectious etiologies of genital ulceration? it is also critical to remember that, although dedicated city/county std clinics are important, the majority (70-80%) of std cases are actually diagnosed and managed by providers in non-std clinic settings.2 this could certainly include a dermatology office where patients might present with: a new pruritic eruption (scabies, pubic lice), a generalized non-pruritic rash (secondary syphilis), a few tender papulovesicles on the ankle (gonococcemia), genital vesicles (herpes), or genital papules or ulcers (syphilis, chancroid, granuloma inguinale). diagnostic pitfalls although 66-75% of std occur in the age range of 15-24, one should never discount the possibility of an std based solely on diagnosis & management skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 103 age. about 40% of those 65-80 years old are sexually active.6 stds have a wide natural variability in morphological appearance, and co-morbidities (such as hiv co-infection or administration of immunosuppressive agents) may further alter “classic” clinical features. clinicians should be aware of atypical std morphologies; examples include: crusted scabies, hypertrophic (or vegetative) genital herpes, and the extra-genital chancre of primary syphilis. furthermore, it is crucial to remember that std diagnosis or verification often requires a multi-faceted approach. appropriate culture, serologic testing, direct microscopic examination of exudate or scrapings, darkfield preparation, and skin biopsy with special or immunoperoxidase stains may be required; as available, molecular diagnostics (polymerase chain reaction, nucleic acid amplification testing and genotyping) may also be employed. in addition, aside from testing those with “lesions” or highly suggestive symptoms, screening tests should be entertained for those who are asymptomatic but at notably increased demographic risk. screening guidelines, by disease state and crossreferenced by demographic classification (men, women, msm, pregnant women, and hiv positive), are enumerated elsewhere.7 therapeutic pearls standard std treatment protocols /guidelines are well documented elsewhere.8 this information is available in multiple formats, including: both an apple and an android cellphone app, a wall chart, a pocket guide, a freely downloadable print version, and online, as needed. reviewing all treatment recommendations is beyond the scope of this brief summary, but select items are certainly worth noting. early infectious syphilis remains amenable to treatment with intramuscular benzathine penicillin g in a single dose of 2.4 million units. however, in recent years, there have been intermittent shortages of this antibiotic throughout the world. the second line of treatment for primary, secondary and early latent infectious syphilis is oral doxycycline in a dose of 100mg twice daily for 14 days. a regimen of minocycline 100mg twice daily for 28 days also appears to be as effective, if not more so, compared to benzathine penicillin g.9 a not uncommon presentation of urethral gonorrhea is the so-called “bull head clap,” which presents as striking edema of the distal penile shaft, extending into the coronal sulcus, with or without dysuria or urethral discharge. uncomplicated gonococcal infections are treated with dual, single-dose antibiotic administration: intramuscular ceftriaxone 250 mg plus azithromycin 1.0g orally. treatment of gonorrhea has been complicated by the development of antimicrobial resistance, most recently high level cephalosporin resistance, especially in europe (spain, france) and asia (japan).8 apparent treatment failures should be immediately referred to specialized std clinics for further investigation and therapy. herpes simplex type 2, the most common cause of herpes progenitalis, typically remains sensitive to acyclovir and its analogues. ongoing suppressive therapy (e.g. valacyclovir 500-1000mg daily) has multiple benefits. these include: reduction in overt outbreaks, reduction in frequency of asymptomatic viral shedding and reduced disease transmission to sexual partners.10 because acyclovir can precipitate in the renal tubules leading to kidney damage, each dose should be taken with a full 8 ounce glass of water. while acyclovir resistance is exceedingly rare in normal hosts, co-infection with hiv may lead to resistance rates ranging from 2.5-16%.11 skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 104 treatment of persistent, acyclovir-resistant infections requires creative intervention, such as application of ophthalmic trifluridine, compounded 1% cidofovir, or 5% topical imiquimod; cryosurgery or electrosurgery; intravenous foscarnet or combinations of the above.12 the diagnosis of anogenital warts is usually made by visual inspection, although a confirmatory biopsy is indicated if lesions are atypical (e.g., pigmented or indurated).8 systematic reviews and metaanalyses of therapeutic modalities are quite difficult due to: heterogeneous treatment methods, a high degree of bias in many studies, and considerable statistical overlap among results.13 thus, numerous publications fail to establish a clear therapeutic hierarchy, especially when clearance rates, recurrence rates and risk of adverse events are all considered concurrently. the best recommendation is likely to administer both locally destructive treatment (cryosurgery, electrosurgery, trichloroacetic or bichloroacetic acid, or laser ablation) in combination with topical immunotherapy (imiquimod 5% or 3.75% creams, sinecatechins 15% ointment, 5% 5flurorouracil cream, or podofillotoxin 0.5% solution). for small numbers of warts, destructive therapy is utilized first followed by several months of topical therapy; for larger numbers of warts, topical therapy is administered initially, followed by ablative intervention, followed by several additional months of topical therapy.14 as to the precise modality used in each phase of management, that must be individualized and selected based on the number, size, morphology, location, and degree of keratinization of warts. of course, prevention is optimal, and the nanovalent hpv vaccine is highly efficacious in this regard. several recent alterations in vaccine regimen should be highlighted. vaccine is now indicated from age 9 until age 45 (instead of age 26), and only two shots are recommended when the vaccine is given under age 15. a massive retrospective study recently verified the high degree of safety associated with the nanovalent hpv vaccine.15 pubic lice can be treated with permethrin 1% cream rinse applied to the affected areas and washed off after 10 minutes or with malathion 0.5% lotion applied to the affected areas and washed off after 8–12 hours. scabies can be treated with permethrin 5% cream applied to all areas of the body from the neck down and washed off after 8–14 hours. for both pediculosis and scabies, oral ivermectin can be used in a dose of 200 mcg/kg, given twice, two weeks apart.8 for crusted scabies, the following regimen may be utilized: 5% topical permethrin cream (full-body application to be repeated daily for 7 days then twice weekly until cure), and concomitant administration of oral ivermectin (200 mcg/kg) on days 1,2,8,9, and 15; additional ivermectin treatment on days 22 and 29 might be required for severe cases.16 chancroid and donovanosis are currently vanishingly rare in the united states. lymphogranuloma venereum has enjoyed a resurgence due to a new serovar (l2b), and may present as perirectal itching, discharge or erosion. this disorder remains sensitive to oral doxycycline (100mg twice daily). additional considerations most often, partners are notified by the index case, although public health authorities usually perform epidemiologic tracing and notification for syphilis. expedited partner therapy (index case is given drug or a prescription for use by sexual contacts) should be considered under the circumstances where this strategy is allowable by law. all persons who seek evaluation and treatment for stds should skin march 2020 volume 4 issue 2 copyright 2020 the national society for cutaneous medicine 105 be screened for hiv infection; such screening should be routine, regardless of whether or not the patient reports any specific behavioral risks for hiv infection.8 hiv testing, however, must be voluntary and free of coercion. clinicians must also report std cases diagnosed in the private or academic setting to public health authorities, as required by state law. finally, barrier protection (condom use) should be recommended for those who contract an std, understanding that failure rate due to slippage or breakage is about 1-2%, even with proper use; sex acts for which lubricant was used have a lower failure for both anal and vaginal sex.17 conflict of interest disclosures: none funding: none corresponding author: ted rosen, md professor of dermatology baylor college of medicine houston, texas phone: 713-794-7129 fax: 713-794-7863 email: vampireted@aol.com references: 1. world health organization. report on global sexually transmitted infection surveillance 2018. accessible at: https://www.who.int/reproductivehealth/publicatio ns/stis-surveillance-2018/en/ 2. centers for disease control and prevention (cdc). sexually transmitted disease surveillance 2018. downloadable report accessible at: https://www.cdc.gov/std/stats18/stdsurveillance 2018-full-report.pdf 3. european centre for disease prevention and control (ecdc). syphilis and congenital syphilis in europe a review of epidemiological trends (2007–2018) and options for response. accessible at: https://www.ecdc.europa.eu/en/publicationsdata/syphilis-and-congenital-syphilis-europereview-epidemiological-trends-2007-2018 4. shinkai k, bauchner h. celebrating the 100th anniversary of jama dermatology as a publication of the american medical association, 1920 to 2020. jama dermatol. 2020 jan 8. doi: 10.1001/jamadermatol.2019.3776. 5. rosen t. syphilis and the dermatologist. cutis. 2017;100(5):279-280. 6. university of michigan national poll on healthy aging, may 2018. sex after 65. accessible at: https://medicine.umich.edu/dept/intmed/news/arc hive/201805/national-poll-healthy-aging-may2018-report-sex-after-65 7. centers for disease control and prevention (cdc). screening recommendations and considerations referenced in treatment guidelines and original sources. accessible at: https://www.cdc.gov/std/tg2015/screeningrecommendations.htm 8. centers for disease control and prevention (cdc). 2015 sexually transmitted diseases treatment guidelines. accessible at: https://www.cdc.gov/std/tg2015/default.htm 9. shao ll, guo r, shi wj, et al. could lengthening minocycline therapy better treat early syphilis? medicine (baltimore).2016;95(52):e5773. doi:10.1097/md.0000000000005773 10. corey l, wald a, patel r, et al. once-daily valacyclovir to reduce the risk of transmission of genital herpes. n engl j med. 2004;350(1):11-20. 11. frobert e, burrel s, ducastelle-lepretre s, et al. resistance of herpes simplex viruses to acyclovir: an update from a ten-year survey in france. antiviral res. 2014;111:36-41. 12. chilukuri s, rosen t. management of acyclovirresistant herpes simplex virus. dermatol clin. 2003;21(2):311-20. 13. bertolotti a, milpied b, fouéré s, et al. local management of anogenital warts in immunocompetent adults: systematic review and pooled analysis of randomized-controlled trial data. j am acad dermatol. 2019;81(5):1203-1204 14. o'mahony c, gomberg m, skerlev m, et al. position statement for the diagnosis and management of anogenital warts. j eur acad dermatol venereol. 2019;33(6):1006-1019 15. shimabukuro tt, su jr, marquez pl, et al. safety of the 9-valent human papillomavirus vaccine. pediatrics. 2019 dec;144(6). pii: e20191791; doi: 10.1542/peds.2019-1791 16. ortega-loayza ag, mccall co, nunley jr. crusted scabies and multiple dosages of ivermectin. j drugs dermatol. 2013;12(5):584-5. 17. siegler aj, rosenthal em, sullivan ps, et al. levels of clinical condom failure for anal sex: a randomized cross-over trial. eclinicalmedicine. 2019 oct 31;17:100199. doi:10.1016/j.eclinm.2019.10.012 mailto:vampireted@aol.com https://www.who.int/reproductivehealth/publications/stis-surveillance-2018/en/ https://www.who.int/reproductivehealth/publications/stis-surveillance-2018/en/ https://www.ecdc.europa.eu/en/publications-data/syphilis-and-congenital-syphilis-europe-review-epidemiological-trends-2007-2018 https://www.ecdc.europa.eu/en/publications-data/syphilis-and-congenital-syphilis-europe-review-epidemiological-trends-2007-2018 https://www.ecdc.europa.eu/en/publications-data/syphilis-and-congenital-syphilis-europe-review-epidemiological-trends-2007-2018 https://medicine.umich.edu/dept/intmed/news/archive/201805/national-poll-healthy-aging-may-2018-report-sex-after-65 https://medicine.umich.edu/dept/intmed/news/archive/201805/national-poll-healthy-aging-may-2018-report-sex-after-65 https://medicine.umich.edu/dept/intmed/news/archive/201805/national-poll-healthy-aging-may-2018-report-sex-after-65 https://www.cdc.gov/std/tg2015/screening-recommendations.htm https://www.cdc.gov/std/tg2015/screening-recommendations.htm https://www.cdc.gov/std/tg2015/default.htm skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 591 brief articles mycobacterium kansasii infection overlying tattoo pigment in an immunocompromised patient rohit gupta, ba1, jennifer c. martin, md2, carina a. wasko, md1,2 1school of medicine, baylor college of medicine, houston, tx 2department of dermatology, baylor college of medicine, houston, tx atypical mycobacterium infections are those caused by mycobacteria other than mycobacterium tuberculosis and mycobacterium leprae.1 the incidence of these infections has steadily grown over the past decades, and it is well-known that the risk of progressive disease increases with immunodeficiency.2 eleven species organized into four groups have been identified as causes of cutaneous atypical mycobacterium infections.1 given the presentation of cutaneous mycobacterial infections varies based on the causative organism and can mimic other diseases, diagnosis of these skin lesions is often delayed.1 this may lead to progression of disease; therefore, it is imperative that providers maintain clinical suspicion of atypical mycobacterium infections among immunocompromised patients and be familiar with presentations of disease. here, we present a case of mycobacterium kansasii infection overlying long-standing tattoo pigment in an immunocompromised individual with no systemic signs of infection. a 41-year-old african american woman presented to the emergency department for a 3-month history of progressive and painful skin lesions on her extremities. during her evaluation, she was noted to have verrucous papules and nodules coalescing into plaques within the tattoos on her right forearm and left shin (figure 1). she reported that the tattoos were obtained from different tattoo parlors years ago. the abstract the incidence of atypical mycobacterial infections has steadily grown over the past decades, and it is well-known that the risk of progressive disease increases with immunodeficiency. while rare, tattoo pigment can serve as a nidus for atypical mycobacterium infection in immunocompromised individuals. here, we present a case of a 41-year-old immunocompromised female who presented with verrucous plaques overlying long-standing tattoos in multiple locations. the patient’s lesions were biopsied and sent for board-range polymerase chain reaction revealing infection with mycobacterium kansasii, a slow-growing atypical mycobacterium that rarely causes cutaneous disease without systemic symptoms. early recognition and treatment of cutaneous m. kansasii is important to prevent progression of disease. introduction case presentation skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 592 figure 1. verrucous lesions on the right forearm confined to the area of the patient’s tattoo. patient had a known history of hiv, was not on anti-retroviral therapy at the time, and presented with a cd4 count of 13. the patient denied any other complaints, including chest pain, shortness of breath, cough, and night sweats. outside of the patient’s cutaneous lesions, physical exam was unremarkable. a punch biopsy of the lesion on the left shin demonstrated extensive granuloma formation in the dermis with focal necrosis and positive acid-fast bacillus (afb) staining (figure 2). the patient’s tissue was sent to the university of washington medical center for broad-range polymerase chain reaction (pcr), which was positive for mycobacterium kansasii. the patient was continued on isoniazid, rifabutin, and ethambutol after being empirically treated with azithromycin, pyrazinamide, isoniazid, rifabutin, and ethambutol. in the subsequent 3 months, the patient developed additional painful nodules on the palms, generalized lymphadenopathy, pulmonary nodules, and sclerotic lesions on the sternum, all likely sequelae of disseminated mycobacterium kansasii, with confirmation following repeat biopsy. thus, azithromycin was added back to the treatment regimen given concern for rifampin-resistance, and the patient was documented to have improvement at the two month follow-up. atypical mycobacterial infections overlying tattoo pigment are rare, with cases mostly stemming from sporadic outbreaks.3 these infections most commonly present shortly after placement of the tattoo on the skin.4 they are thought to originate from mycobacterial contamination of tattoo equipment or the tattoo pigment, or bacterial inoculation of breaks in the skin surface caused by the tattooing process, and they can occur in both healthy and immunocompromised individuals.4 we describe a case of m. kansasii infection occurring over long-standing black tattoo pigment in an hiv-positive patient. m. kansasii is a slow-growing, acid-fast bacillus found in water reservoirs, swimming pools, and tap water most commonly in the southern and central united states. most infections occur in middle-aged men and present much like m. tuberculosis – productive cough, night sweats, and chest pain.5 m. kansasii rarely causes cutaneous lesions compared to faster-growing discussion skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 593 figure 2. (a) histopathology revealed granulomatous inflammation with scattered associated neutrophils (h&e, 200x) (b) acid-fast bacilli are present (afb stain, 1000x). counterparts such as m. avium complex, m. abscessus-chelonae complex, and m. fortuitum; however, skin lesions are often the first sign of disseminated disease.6 cutaneous infection may manifest as verrucous lesions, nodules, pustules, erythematous plaques, and ulcers.5 in the immunocompromised host, atypical cutaneous manifestations can develop including diffuse abscesses, seromas, and cellulitis, often with divergent histological findings such as the absence of granulomas.7 this can delay diagnosis and treatment, potentially leading to the development of systemic complications such as sepsis. lesion discharge culturing is the gold standard diagnosis of cutaneous m. kansasii infection.6 biopsy of lesions may also be performed, and histopathology shows acidfast bacilli and granuloma formation with mixed inflammatory infiltrate.8 epidermal necrosis and abscess formation may also be present.1 these histological findings are identical to those of cutaneous m. tuberculosis infection; therefore, although biopsy can secure a diagnosis of mycobacterial infection, isolation of the organism must be done to diagnose m. kansasii infection specifically. in cases where sufficient material for culturing is not available, broad-range polymerase chain reaction (pcr) from a tissue sample can be used to identify the organism. the prognosis of cutaneous m. kansasii infection worsens with progressive dissemination and immunosuppression, and outcomes vary based on individual response to treatment.9 traditional therapy includes at least one year of rifampin, isoniazid, ethambutol, and pyridoxine;10 however, prior to the initiation of therapy, susceptibility testing with rifampin is recommended given that many strains of m. kansasii demonstrate multi-drug resistance.6 in cases of therapy resistance, clarithromycin or azithromycin must be substituted.10 to further complicate treatment, rifampin should skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 594 be replaced by rifabutin in hiv-positive patients who are taking non-nucleoside reverse transcriptase inhibitors (nnrti) or protease inhibitors in order to minimize drug interaction.5 while atypical mycobacterium infection is one explanation for the development of verrucous plaques on long-standing tattoo pigment, the differential for such lesions should include sarcoidosis, hpv-associated warts (i.e., verrucae), rupioid syphilis, pseudoepitheliomatous hyperplasia, blastomycosis, chromoblastomycosis, and rarely squamous neoplasms. although careful history and physical exam may identify systemic symptoms associated with each etiology, a definitive diagnosis is usually reached following culturing or skin biopsy. we present a case of cutaneous mycobacterium kansasii infection overlying tattoo pigment in an immunocompromised individual. this case demonstrates the importance of considering atypical mycobacterium infections in patients not only with new tattoos, but also in longstanding tattoo pigment. conflict of interest disclosures: none funding: none corresponding author: jennifer c. martin department of dermatology 1977 butler blvd houston, tx 77030 email: jennifer.martin@bcm.edu references: 1. bhambri s, bhambri a, del rosso jq. atypical mycobacterial cutaneous infections. dermatol clin. 2009;27(1):63-73. doi:10.1016/j.det.2008.07.009 2. khan k, wang j, marras tk. nontuberculous mycobacterial sensitization in the united states: national trends over three decades. am j respir crit care med. 2007;176(3):306-313. doi:10.1164/rccm.200702-201oc 3. mudedla s, avendano ee, raman g. nontuberculous mycobacterium skin infections after tattooing in healthy individuals: a systematic review of case reports. dermatol online j. 2015;21(6). 4. conaglen pd, laurenson if, sergeant a, thorn sn, rayner a, stevenson j. systematic review of tattoo-associated skin infection with rapidly growing mycobacteria and public health investigation of a cluster in scotland, 2010. euro surveill. 2013;18(32):20553. doi:10.2807/15607917.es2013.18.32.20553 5. akram sm, rawla p. mycobacterium kansasii. in: statpearls. treasure island (fl)2020. 6. griffith de, aksamit t, brown-elliott ba, et al. an official ats/idsa statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. am j respir crit care med. 2007;175(4):367-416. doi:10.1164/rccm.200604-571st 7. breathnach a, levell n, munro c, natarajan s, pedler s. cutaneous mycobacterium kansasii infection: case report and review. clin infect dis. 1995;20(4):812-817. doi:10.1093/clinids/20.4.812 8. hsu py, yang yh, hsiao ch, lee pi, chiang bl. mycobacterium kansasii infection presenting as cellulitis in a patient with systemic lupus erythematosus. j formos med assoc. 2002;101(8):581-584. 9. sprague j, leibowitz m, chiu mw. cutaneous infection with mycobacterium kansasii in a patient with myelodysplastic syndrome and sweet syndrome. cutis. 2015;96(1):e10-12. 10. han sh, kim km, chin bs, et al. disseminated mycobacterium kansasii infection associated with skin lesions: a case report and comprehensive review of the literature. j korean med sci. 2010;25(2):304-308. doi:10.3346/jkms.2010.25.2.304 conclusion mailto:jennifer.martin@bcm.edu skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 575 brief articles complete histologic response of regionally metastatic melanoma treated with intralesional interleukin 2, topical retinoid and imiquimod william c. schaffenburg, md1, joshua w davis, md2, nicholas f. logemann, do, faad3, meagan simpson, md, msc1 1dermatology department, walter reed national military medical center, bethesda, md 2pathology department, walter reed national military medical center, bethesda, md 3dermatology department, naval medical center san diego, ca metastatic melanoma is a difficult malignancy to manage, and the methods used to treat it have significantly changed over the past two decades. we present the use of older medications in a previously successful newer modality that can achieve results suggestive of cure. this method has shown repeated success in patients who desire to avoid surgery, or who lack apparent response to newer standard of care medical treatment. this demonstrates that the method continues to work despite use of check point inhibitor immunotherapy, and check point inhibitor medication side effects requiring further immunosuppression. a 74-year-old indian man presented with a growing nodule on his right parietal scalp, which biopsy proved to be a 3.8mm invasive melanoma. histological examination of punch biopsies before treatment showed dermal nodules of heavily pigmented, malignant melanocytes. the dermatopathologist noted that considerations included locally recurrent disease at the site of prior lymphadenectomy and possibly in-transit or distant cutaneous metastatic foci (figure 2). further testing revealed a valine to lysine mutation within the braf gene (v600k). he was initially treated with wide local excision and sentinel lymph node biopsy which was positive in five levels of lymph nodes. he then underwent right neck lymph node dissection with a free-flap graft from his left forearm to close the scalp defect. positron emission tomography (pet) showed no evidence of systemic disease. the patient responded to adjuvant monthly nivolumab post-surgically, but was noted to develop persistent adrenal insufficiency, which required daily oral hydrocortisone supplementation. nine months later, multiple black papules were noted in and around the surgical scars of his right neck (figure 1). multiple biopsies showed melanoma, consistent with possible "surgical seeding" due to lack of epidermal involvement (figure 2). repeat imaging showed evidence of only cutaneous disease. the patient was switched from introduction case presentation skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 576 figure 1. progression of cutaneous melanocytic lesions over course of interleukin treatment. (a) therapy two weeks into treatment with il-2; (b)therapy five weeks into treatment with il-2; (c) therapy one week post therapy with il-2; (d) therapy four weeks post therapy with il-2. nivolumab to pembrolizumab and ipilimumab with a goal of increased immunologic response, but did not gain significant benefit. his daily oral hydrocortisone dependency precluded him from other systemic treatments, such as tumor infiltrating lymphocytes (til), or clinical trials. due to skin-limited disease, a regimen of imiquimod, tretinoin 0.025% cream (with intermittent increase to tazarotene 0.1% gel as tolerated), and intralesional and perilesional interleukin-2 (il-2) injections was initiated. the regimen per shi et al. resulted in leukoderma, ulceration and irritation to the area as intended.1 with daily application of topical treatment, plus biweekly il-2 injections, the local metastases slowly regressed over the next six weeks (figure 1). biopsies of browna. b. c. d. skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 577 figure 2. comparison of biopsies before (a) and after (b) treatment, showing no further evidence of abnormal appearing melanocytes with residual melanophages. (h&e, 20x) black macules post-therapy consistently demonstrated superficial clusters of melanophages with melanin incontinence, melanophages, cicatrix, and evidence of regression, consistent with successful localized treatment (figure 2). initial dosing of il-2 was performed with monitoring in an infusion clinic at a starting dose of 5 million units with subsequent increase in concentration to a maximum of 22 million units over next three injections, which were performed in the dermatology clinic.1,3 with the advent of immunotherapy, systemic il-2 treatment has fallen out of favor for treatment of metastatic melanoma due to poorly tolerated side effects, such as rigors, chills, and hemodynamic instability requiring hospital admission. intralesional delivery has allowed patients to receive much higher localized doses and, depending on disease location, promising results.1-3 il-2 is thought to stimulate proliferation and activation of humoral and cell mediated immunologically active cells through the differentiation of cd4+ t cells and to stimulate effector t cell generation and differentiation into memory cells for cd8+ t cells, resulting in tumor lysis.1,4 applying topical retinoids increases the rate of keratinocyte maturation and potentiates imiquimod penetration, which in turn upregulates toll-like receptors seven and eight as well as cytokines, such as tumor necrosis factor alpha, and cytotoxic tcell responses.1,2 previous small studies have treated patients with intralesional il-2 injections, imiquimod and topical retinoids with good results, but many of the participants had not received any immunotherapy prior to treatment, whereas our patient had already been treated with two programmed cell death protein-1 inhibitors (nivolumab and pembrolizumab) and a cytotoxic t-lymphocyte associated protein 4 inhibitor (ipilimumab).1 this report demonstrates procedural adjunctive therapies that dermatologists can offer to patients with cutaneous metastases as an adjunct to immunomodulatory therapy or for patients whose post-immunotherapy discussion conclusion a. b. skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 578 endocrinopathies limit their candidacy for til therapy or clinical trials. conflict of interest disclosures: none funding: none corresponding author: william schaffenburg, md dermatology department, walter reed national military medical center 8901 wisconsin ave, bethesda, md 20889 phone: 301-295-4551 fax: 301-295-5164 email: william.c.schaffenburg.mil@mail.mil references: 1. shi vy, tran k, patel f, et al. 100% complete response rate in patients with cutaneous metastatic melanoma treated with intralesional interleukin (il)-2, imiquimod, and topical retinoid combination therapy: results of a case series. j am acad dermatol. 2015 oct;73(4):645-54. doi: 10.1016/j.jaad.2015.06.060. epub 2015 aug 7. 2. miki garcia m, ono y, martinez s, et al. complete regression of subcutaneous and cutaneous metastatic melanoma with high-dose intralesional interleukin 2 in combination with topical imiquimod and retinoid cream melanoma research. 21(3):235–243, june 2011 doi: 10.1097/cmr.0b013e328345e95e, pmid: 21464773 3. green ds, bodman-smith ag, fischer md. “phase i/ii study of topical imiquimod and intralesional interleukin-2 in the treatment of accessible metastases in malignant melanoma” bj derm, 2007 feb; 156(2): 337-345. doi: https://doi.org/10.1111/j.1365-2133.2006.07664.x 4. boyman o, sprent j. the role of interleukin-2 during homeostasis and activation of the immune system. nat rev immunol. 2010(12):180–190. https://doi.org/10.1038/nri3156 mailto:william.c.schaffenburg.mil@mail.mil https://doi.org/10.1111/j.1365-2133.2006.07664.x acknowledgements: medical writing support was provided by prescott medical communications group (chicago, il) with financial support from ortho dermatologics; ortho dermatologics is a division of bausch health us, llc | presented at winter clinical dermatology conference 2020 • january 17-22, 2020 • kohala coast, hi synopsis ◾ topical corticosteroids are the mainstay of psoriasis treatment, particularly for mild disease,1 though topical treatments as part of combination therapy for moderate-to-severe psoriasis is becoming increasingly common ◾ however, continuous use of topicals may be limited due to application-site adverse events (aes)1 ◾ recent phase 3 clinical data have demonstrated efficacy and tolerability of a fixed combination lotion containing halobetasol propionate 0.01% and tazarotene 0.045% (hp/taz; duobrii® ortho dermatologics, bridgewater, nj) in patients with moderate-to-severe localized plaque psoriasis2,3 objective ◾ to investigate aes and local skin reactions following long-term use of hp/taz lotion methods ◾ this was a 1-year multicenter, open-label study (nct02462083) in patients with moderate-to-severe plaque psoriasis ◾ participants were treated with hp/taz lotion once-daily for 8 weeks and intermittently as needed in 4-week intervals (figure 1) • at week 8, treatment was stopped for participants that achieved treatment success; those who did not reach treatment success were treated for 4 additional weeks • all participants were re-evaluated at week 12; those demonstrating ≥1-grade improvement in baseline investigator’s global assessment (iga) continued the study and were subsequently managed in 4-week cycles, either treated with hp/taz lotion once-daily if they had not achieved treatment success or receiving no treatment until the next evaluation if they had achieved treatment success ◾ maximum continuous exposure was 24 weeks figure 1. open-label study design oncedaily hp/taz successa treatment stopped for 4 weeks improvementb continued study and managed in 4-week cycles for up to 1 year, with patients re-evaluated every 4 weeks for treatment successa no improvement discontinued from study no success continued once-daily hp/taz for 4 weeks day 0 week 8 evaluated for treatment successa week 12 evaluated for ≥1-grade improvement from baseline iga week 24 if continuous treatment was received, iga score of 0 or 1 needed to continue study 1 year maximum continuous exposure was 24 weeks. atreatment success defined as score of 0 or 1 on iga. bimprovement defined as ≥1-grade improvement from baseline iga. hp/taz, halobetasol propionate 0.01%/tazarotene 0.045%; iga, investigator’s global assessment. safety and tolerability of fixed combination halobetasol propionate 0.01% and tazarotene 0.045% (hp/taz) lotion in patients with moderate-to-severe plaque psoriasis: results from a 1-year, open-label study figure 2. local skin reactions over time, by severity (safety population) 100% 80% 60% 40% 20% 0% none mild moderate severe p e rc e n ta g e o f p a rt ic ip a n ts baseline week 12 week 24 week 36 week 52 itching baseline week 12 week 24 week 36 week 52 dryness baseline week 12 week 24 week 36 week 52 burning/stinging figure 3. incidence of local skin reactions over time (safety population) 3% 2% 1% 0% p e rc e n ta g e o f p a rt ic ip a n ts 0.5% 1.7% 1.4% 0.9% 0% 1.1% 1.3% 0.8% 0.9% 0.7% 0.2% 0.8% 0.6% 0% 0% 0.4% 1.5% 1.1% 0.4% 0% baseline week 12 week 24 week 36 week 52 skin atrophy baseline week 12 week 24 week 36 week 52 striae baseline week 12 week 24 week 36 week 52 telangiectasias baseline week 12 week 24 week 36 week 52 folliculitis skin reactions ◾ select local signs/symptoms showed marked improvements in severity of itching, dryness, and burning/stinging over the study course; greatest improvement was for itching (figure 2) ◾ incidence of treatment-emergent grade 3 local skin reactions was 22.2% for itching, 6.9% for dryness, and 9.8% for burning/stinging ◾ incidence of other local skin reactions are shown in figure 3 • incidence peaked at 2.3% for skin atrophy (week 8), 2.7% for folliculitis (week 8), and 1.5% for striae and telangiectasias (week 28) ◾ local skin reactions most frequently reported as aes were application site folliculitis (14 participants [2.5%]; 1 discontinued) and application site atrophy (4 participants [0.7%]; 1 discontinued); no participant reported striae or telangiectasias aes ◾ most local skin reactions were transient and resolved prior to end of dosing conclusions ◾ no clinically meaningful trends in local skin reactions were observed following long-term use of a fixed combination hp 0.01%/taz 0.045% lotion ◾ the types of teaes were consistent with those of a corticosteroid and retinoid product, but occurred at lowerthan-anticipated frequencies, suggesting a favorable long-term safety profile for hp/taz lotion references 1. menter a, et al. j am acad dermatol. 2009;60(4):643-659. 2. stein gold l, et al. j am acad dermatol. 2018;79(2):287-293. 3. sugarman jl, et al. j drugs dermatol. 2018;17(8):855-861. author disclosures dr. mark g lebwohl is an employee of mount sinai and receives research funds from abbvie, amgen, arcutis, astrazeneca, boehringer ingelheim, celgene, clinuvel, eli lilly, incyte, janssen research & development llc, kadmon corp llc, leo pharmaceuticals, medimmune, novartis, ortho dermatologics, pfizer, sciderm, ucb inc, and vidac.; is a consultant for allergan, almirall, arcutis inc, avotres therapeutics, birchbiomed inc, boehringer-ingelheim, bristol-myers squibb, cara therapeutics, castle biosciences, corrona, dermavant sciences, foundation for research and education in dermatology, inozyme pharma, leo pharma, meiji seika pharma, menlo, mitsubishi, neuroderm, pfizer, promius/dr. reddy’s laboratories, theravance, and verrica. dr. jeffery sugarman is a consultant for ortho dermatologics, bausch health, regeneron, sanofi, and pfizer. dr. david m pariser has served as consultant to atacama therapeutics, bickel biotechnology, biofrontera ag, celgene, dermira, leo, regeneron, sanofi, tdm surgitech, theravida, and ortho dermatologics; investigator for abbott laboratories, almirall, amgen, aobiome, asana biosciences, bickel biotechnology, celgene, dermavant, dermira, eli lilly, leo, menlo therapeutics, merck & co., novartis, novo nordisk a/s, ortho dermatologics, pfizer, regeneron, and stiefel; on advisory board for pfizer; and on the data monitoring board for bms. dr. jerry bagel is an investigator and speaker for ortho dermatologics. dr. tina lin is an employee of ortho dermatologics and may hold stock and/or stock options in its parent company. dr. robert israel is an employee of bausch health us, llc and may hold stock and/or stock options in its parent company. results participants and exposure ◾ a total of 550 participants were included in the safety population • mean age was 51.9 years (range: 19 to 87 years); 65.6% were male and 86.0% were white • baseline iga was moderate (3; 86.5%) or severe (4; 13.5%); median affected body surface area was 5% ◾ median amount of study drug used was 256.5 g, median length of exposure was 172 days, and median number of applications was 164 treatment-emergent adverse events ◾ over half of participants experienced treatment-emergent adverse events (teaes) during the year-long study, primarily during the first 12 weeks (table 1) • most teaes were mild or moderate • none of the serious adverse events (saes) were related to treatment ◾ the most common teaes related to study drug were application site reactions (table 1) table 1. treatment-emergent adverse event summary (safety population) 0-12 weeks (n=527) >12-24 weeks (n=392) >24-36 weeks (n=239) >36 weeks-eos (n=219) total (n=550) number of teaes, no. 395 194 98 71 758 participants with ≥1 teae, n (%) 223 (42.3) 130 (33.2) 61 (25.5) 43 (19.6) 314 (57.1) discontinued study drug due to teae, n (%) 30 (5.7) 9 (2.3) 2 (0.8) 0 41 (7.5) participants with ≥1 sae,a n (%) 6 (1.1) 5 (1.3) 5 (2.1) 2 (0.9) 18 (3.3) treatment-related teae, n (%) 120 (22.8) 43 (11.0) 18 (7.5) 8 (3.7) 161 (29.3) teaes by severity, n (%) mild 99 (18.8) 67 (17.1) 28 (11.7) 22 (10.0) 122 (22.2) moderate 101 (19.2) 55 (14.0) 26 (10.9) 16 (7.3) 151 (27.5) severe 23 (4.4) 8 (2.0) 7 (2.9) 5 (2.3) 41 (7.5) most common treatment-related teaes,b n (%) application site dermatitis 38 (7.2) 20 (5.1) 6 (2.5) 2 (0.9) 56 (10.2) application site pruritus 22 (4.2) 6 (1.5) 4 (1.7) 2 (0.9) 33 (6.0) application site pain 24 (4.6) 2 (0.5) 1 (0.4) 1 (0.5) 28 (5.1) application site irritation 10 (1.9) 4 (1.0) 3 (1.3) 1 (0.5) 13 (2.4) anone of the saes were deemed related to treatment; bin >2% of total participants. eos, end of study; sae, serious adverse event; teae, treatment-emergent adverse event. mark g lebwohl, md1; jeffrey sugarman, md, phd2; david m pariser, md3; jerry bagel, md4; tina lin, pharmd5; robert israel, md6 1icahn school of medicine at mount sinai, new york, ny; 2university of california, san francisco, ca; 3virginia clinical research center, norfolk, va; 4psoriasis treatment center of central new jersey, east windsor, nj; 5ortho dermatologics*, bridgewater, nj; 6bausch health us, llc*, bridgewater, nj *bausch health us, llc is an affiliate of bausch health companies inc. ortho dermatologics is a division of bausch health us, llc. microsoft word july 2020 rlet 873 proof returned.docx skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 328 research letters a survey-based study on maintenance of certification programs during grand rounds at ut southwestern medical center anisha guda1, travis vandergriff, md2, melissa m. mauskar, md2 1ut health san antonio long school of medicine, san antonio, tx 2department of dermatology, ut southwestern medical center, dallas, tx to the editor: maintenance of certification (moc) is a recertification program required by the american board of dermatology (abd) for dermatologists.1 the program was created to supplement continuing medical education (cme) by giving physicians the opportunity to participate in meaningful practice improvement and self-assessment compared to their peers while also providing a mechanism for physician self-regulation. one component of moc is a periodic selfassessment where dermatologists are required to complete three 100-question self-assessment modules over a 10-year period.2 moc programs assess knowledge, communication, patient safety, and practice performance.3 in many cases, these activities are obtained at national meetings or through practice improvement modules. the american academy of dermatology has attempted to make the process of obtaining moc credit easier by providing jaad abstract background: maintenance of certification (moc) is a recertification program required by the american board of dermatology (abd). the program was created because continuing medical education (cme) was viewed as inadequate in keeping physicians’ knowledge up to date. in july 2016, utsw incorporated moc content into grand rounds. objective: to identify whether dermatologists at utsw find moc grand rounds to be useful and whether this process could be utilized in other institutions. methods: a five question survey was piloted by a few dermatologists at utsw. the survey was emailed to dermatologists who attended the moc grand rounds. three questions were scored on a scale of 1-6 (1= strongly disagree, 2=moderately disagree, 3= neutral, 4= mildly agree, 5= moderately agree, 6=strongly agree) with 2 free response questions. results: 13/20 dermatologists responded to the survey (65% response rate). 11/13 dermatologists (84.6%) reported that moc at grand rounds is valuable to them. 11/13 dermatologists (84.6%) reported that other dermatology programs should incorporate this method of obtaining moc credit. 9/13 dermatologists (69.2%) reported audience response sessions improve the grand rounds experience. conclusion: dermatologists found the moc content to be useful when incorporated into grand rounds. skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 329 table 1. survey results on likert scale regarding moc grand rounds at utsw quizzes, case challenges, and questions of the week.1 most academic medical centers have regular clinical conferences (grand rounds) where both faculty and residents discuss difficult cases. these conferences are the ideal avenue for obtaining self-assessment moc (sa moc) credit given the inherent nature of discussion: application of multigenerational clinical experiences and identification of ways to improve patient care. in june 2016, we applied to receive sa moc 2 credit at monthly grand rounds. from july 2016 to july 2017, the university of texas at southwestern medical center (utsw) incorporated sa moc content into grand rounds. once a month, interesting clinical cases were presented to the group. at the end of each patient case, there were at least three multiple choice clinical questions presented to the audience. the audience then responded using poll everywhere (an internet-based audience response system) to see how they answered compared to their peers. participants could earn up to 10 credits in 1 hour for their participation. after a 12-month pilot period, a survey was sent to participants to identify whether this activity was useful and if they felt this method of obtaining moc credit could be utilized in other institutions. a five-question survey was developed and piloted by the authors and emailed to dermatologists who attended moc grand rounds at utsw medical center. the survey questions consisted of three questions that were scored on a likert scale of 1-6 (1= strongly disagree, 2=moderately disagree, 3= neutral, 4= mildly agree, 5= moderately agree, 6=strongly agree) and 2 free response questions. results were collected and analyzed through survey monkey. 13 out of 20 dermatologists responded to the survey (65% response rate). the survey questions and responses are shown in table 1 and figure 1. respondents reported that they liked grand rounds oriented to moc. 11 out of 13 dermatologists (84.6%) reported that moc at grand rounds is of value to them. 11 out of 13 dermatologists (84.6%) reported that other dermatology programs should incorporate this method of obtaining moc credit. additionally, 9 out of 13 dermatologists (69.2%) reported that audience response sessions improve the grand rounds experience. it should be noted that the percentages mentioned were summations of those who chose 4 (mildly agree), 5 (moderately agree), or 6 (strongly agree) on the likert scale for each question. dermatologists also mentioned that they desired more live patient presentations, faculty present, and audience participation 1 strongly disagree 2 moderately disagree 3 neutral 4 mildly agree 5 moderately agree 6 strongly agree audience response sessions improve the grand rounds experience. 0% 0% 30.77% 23.08% 23.08% 23.08% maintenance of certification at grand rounds is of value to me. 0% 0% 15.38% 23.08% 30.77% 30.77% i would recommend other dermatology programs incorporate this method of obtaining moc credit into their grand rounds. 0% 7.69% 7.69% 30.77% 15.38% 38.46% skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 330 during grand rounds. other suggestions to improve grand rounds included more discussion about common diseases and treatment options, more content on cutting edge treatment and evaluation, more outside speakers, usage of dermatologic medications in the elderly and modifications in dosing/considerations in caring for the extremely aged, wound care materials and their evidence, discussion on the effect of sunscreens on coral reefs and evidence, updates on chemoprophylaxis of skin cancers and their indications, usage of white boards, and having someone write out descriptions in real time. the intended goal of maintenance of certification is to help dermatologists improve their overall patient care. departmental grand rounds offers a convenient and beneficial way to receive qualifying credits for moc. dermatologists are able to engage in educational discussion on clinical cases and meet the essential goals of moc. future studies on how other institutions view departmental grand rounds would help determine whether it should be an established practice at academic programs. figure 1. graphical representation of survey results conflict of interest disclosures: none funding: none corresponding author: anisha guda, bs ut health san antonio long school of medicine 7703 floyd curl drive, san antonio tx email: gudav@livemail.uthscsa.edu references: 1. maintenance of certification. american academy of dermatology. retrieved from < https://www.aad.org/education/moc>. 2. horn t. program for maintenance of certification by the american board of dermatology. cutis. 2017;99(6):376-377. 3. stratman e, kirsner rs, and horn td. maintenance of certification in dermatology: what we know, what we don’t. jaad. 2013;69(1):e1-e11. doi: https://doi.org/10.1016/j.jaad.2013.03.033 audience response sessions improves the grand rounds experience 1 2 3 4 5 6 maintenance of certification at grand rounds is of value to me 1 2 3 4 5 6 i would recommend other dermatology programs incorporate this method of obtaining moc credit into their grand rounds 1 2 3 4 5 6 skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 268 brief articles eosinophilic annular erythemasuccessful treatment with dupilumab alina g. zufall, ba1, rung-chi li, do, phd2, barrett j. zlotoff, md3, monica g. lawrence, md2, richard h. flowers, md3 1university of virginia school of medicine, charlottesville, va 2university of virginia department of medicine, division of asthma, allergy and immunology, charlottesville, va 3university of virginia department of dermatologyy, charlottesville, va eosinophilic annular erythema (eae) is a rare eosinophilic dermatosis characterized by resistance to treatment and high rate of relapse.1 there are few reported cases in the literature and no standard treatments. many drugs that work to treat this condition target the type 2 inflammatory response thought to play a predominate role in its pathogenesis. we report a case of eae responsive to the il-4 receptor antagonist, dupilumab. a 57-year-old woman with medical history notable for moderately-persistent, poorly controlled asthma (requiring high dose inhaled corticosteroid/ long acting beta blocker twice daily) presented with a sevenyear history of pruritic arcuate and annular erythematous plaques on the extensor surfaces of the forearms (figure 1). she denied prior trauma or insect bites and had started no new medications prior to the eruption. the rash was refractory to topical corticosteroids, tacrolimus ointment, and various emollients. histologic evaluation demonstrated superficial and deep dermal perivascular and periadnexal mixed inflammatory infiltrate containing a significant number of eosinophils and dermal mucin deposition (figure 2). due to the persistent and recalcitrant nature of the rash, as well as the annular nature of the lesions and lack of flame figures on histology, the patient was diagnosed with eosinophilic annular erythema (eae). further evaluation of the patient revealed a chronic leukocytosis. differential showed no eosinophilia but mild persistent neutrophilia which preceded the eruption. renal and hepatic function were normal. introduction eosinophilic annular erythema (eae) is a rare eosinophilic dermatosis with few documented cases in the literature. it is considered either a distinct entity or subtype of well’s syndrome (eosinophilic cellulitis), but eae, in contrast to well’s syndrome, is characterized by a chronic course and resistance to treatment. therapies with reported efficacy include anti-malarial medications, suplatast tosilate, and dapsone. we report the first adult case of eae to respond to dupilumab, an il-4 receptor antagonist, which targets the type 2 inflammatory response associated with tissue eosinophilia. abstract case report skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 269 figure 1. erythematous plaques on the extensor surfaces of the forearms prior to arrival at out clinic, several medications had been ineffective at treating the patient’s condition, including: dapsone, azathioprine, prednisone, and topical steroids and tacrolimus. the patient was unaware of the doses or duration of these treatments. a full course of dapsone, however, was not able to be completed, as it was poorly tolerated secondary to the development of fatigue. the patient saw some improvement after one month of treatment with doxycycline 100mg twice a day, with a decrease in the size and number of lesions. this did not last, though, and the condition worsened over the next two months of treatment. due to the patient’s extensive history of failed medications, we consulted our allergy colleagues to help with approval for dupilumab, a medication that targets the type 2 inflammatory pathway. this was selected with the goal of treating both the patient’s eae and asthma. the patient was treated with 200mg subcutaneously every two weeks. while the patient’s asthma did not improve, she experienced no adverse reactions to the medication, and, in under two months, the rash resolved (figure 3). she has remained in remission for six months. figure 2. superficial and deep dermal perivascular and periadnexal mixed inflammatory infiltrate containing a significant number of eosinophils and dermal mucin deposition eosinophilic annular erythema (eae) is a rare eosinophilic dermatosis with few reported cases in the literature. eae was first discussion skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 270 figure 3. resolved rash described in the literature in 1999 as a “gyrate erythema” distinct from well’s syndrome due to the lack of blood eosinophilia and “flame figures,” deposits of eosinophil basic protein mixed with degenerated collagen fibers, which are both characteristic findings in well’s syndrome.2 in 2017, nakazato and colleagues also concluded that eae was a histologically distinct entity from well’s syndrome due to localization of eosinophils to the superficial and/or deep dermis and absence of flame figures and vasculitis.3 other reports argue that eae is a subtype of well’s syndrome, as flame figures are sometimes seen in biopsies of later lesions.1,5 nevertheless, distinct entity or subtype, therapeutic options for eae, compared to well’s syndrome, have remain limited. this is likely because, while eae is sometimes selflimited, it is predominantly characterized by a chronic course, high relapse rate, and significant resistance to treatment.1 this is in contrast to well’s syndrome, which often responds dramatically to oral corticosteroids. no single drug has been found to be consistently effective for the treatment of eae, and its relapsing, remitting nature makes true efficacy difficult to determine. therapies with reported efficacy include prednisone plus or minus hydroxychloroquine or cyclosporine, hydroxychloroquine alone, chloroquine, suplatast tosilate, dapsone, and narrowband ultraviolet b (uvb) treatment.1,2,5–7 though the pathogenesis of eae remains unknown, these drugs may work by targeting the type 2 inflammatory response associated with tissue eosinophilia. specifically, chloroquine inhibits eosinophilotaxis and the release of pro-inflammatory cytokines; suplatast tosilate suppresses the production of type 2 cytokines, such as il-4 and il-5 that promote eosinopoeisis; and, dapsone inhibits eosinophil peroxidase.2,5,6 it is not surprising then that dupilumab, an il4 receptor alpha antagonist which blocks il4 and il-13 signaling involved in the type 2 inflammatory response, worked to improve our patient’s eae. to our knowledge, this is the first adult case with response of eae to dupilumab, though similar efficacy was noted in a pediatric case of eae in 2018.8 although skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 271 fda-approved only for atopic dermatitis, asthma, and chronic rhinosinusitis with nasal polyposis, dupilumab has shown efficacy in several dermatologic diseases of the type 2 inflammatory pathway, including allergic contact dermatitis, bullous pemphigoid, and prurigo nodularis.9–11 in summary, our patient experienced a dramatic and lasting improvement with dupilumab. although further studies are certainly necessary to assess the true benefit of this medication for eae and other eosinophilic dermatoses, dupilumab offers a mechanistically compelling therapy for an often refractory condition. conflict of interest disclosures: none funding: none acknowledgments: the authors wish to thank darla low, rn for her help in caring for this patient. corresponding author: alina g. zufall department of dermatology university of virginia 1215 lee street charlottesville, va 22908 phone: 434-924-5115 fax: 434-924-5936 email: agz8pv@hscmail.mcc.virginia.edu references: 1. el-khalawany m, al-mutairi n, sultan m, shaaban d. eosinophilic annular erythema is a peculiar subtype in the spectrum of wells syndrome: a multicentre long-term follow-up study. j eur acad dermatol venereol. 2013;27(8):973-979. doi:10.1111/j.14683083.2012.04616.x 2. kahofer p, grabmaier e, aberer e. treatment of eosinophilic annular erythema with chloroquine. acta derm venereol. 2000;80(1):70-71. doi:10.1080/000155500750012685 3. nakazato s, fujita y, shinkuma s, nomura t, shimizu h. eosinophilic annular erythema is clinically characterized by central pigmentation reflecting basal melanosis: a clinicopathological study of 10 cases. j eur acad dermatol venereol. 2017;31(11):1916-1923. doi:10.1111/jdv.14350 4. howes r, girgis l, kossard s. eosinophilic annular erythema: a subset of wells’ syndrome or a distinct entity? australas j dermatol. 2008;49(3):159-163. doi:10.1111/j.14400960.2008.00456.x 5. kanameishi s, goto k, ogawa m, fukumoto t, tanabe h. efficacy of suplatast tosilate in a case of recurrent eosinophilic annular erythema. int j dermatol. 2018;57(9):e66-e68. doi:10.1111/ijd.13973 6. manriquez j, berroeta-mauriziano d, andinonavarrete r, vera-kellet c. eosinophilic annular erythema: complete clinical response with dapsone. int j dermatol. 2015;54(4):e96-98. doi:10.1111/ijd.12736 7. thomas l, fatah s, nagarajan s, natarajan s. eosinophilic annular erythema: successful response to ultraviolet b therapy. clin exp dermatol. 2015;40(8):883-886. doi:10.1111/ced.12668 8. gordon sc, robinson sn, abudu m, et al. eosinophilic annular erythema treated with dupilumab. pediatr dermatol. 2018;35(4):e255e256. doi:10.1111/pde.13533 9. goldminz am, scheinman pl. a case series of dupilumab-treated allergic contact dermatitis patients. dermatol ther. 2018;31(6):e12701. doi:10.1111/dth.12701 10. kaye a, gordon sc, deverapalli sc, her mj, rosmarin d. dupilumab for the treatment of recalcitrant bullous pemphigoid. jama dermatol. 2018;154(10):1225-1226. doi:10.1001/jamadermatol.2018.2526 11. beck km, yang ej, sekhon s, bhutani t, liao w. dupilumab treatment for generalized prurigo nodularis. jama dermatol. 2019;155(1):118-120. doi:10.1001/jamadermatol.2018.3912 mailto:agz8pv@hscmail.mcc.virginia.edu skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 7 original research what is the true etiology of “recurrent shingles”? ramya vangipuram, md1, harrison p. nguyen, md, mba, mph, dtm2, stephen k. tyring, md, phd, mba1,3 1department of dermatology, mcgovern medical school, houston, texas 2department of internal medicine, baylor college of medicine, houston, texas 3center for clinical studies, houston, texas herpes zoster (shingles), caused by reactivation of latent varicella–zoster virus, is characterized by a painful unilateral vesicular rash in a dermatomal distribution. the incidence and severity of herpes zoster increase with age, in association with a decline in cell-mediated immunity.1 the infection is usually limited to a single occurrence; recurrence is typically characteristic of immune compromise.1 in immunocompetent persons, recurrent herpes zoster is thought to be rare, with an estimated incidence of 1-3%.1 however, many immunocompetent persons report being diagnosed with recurrent herpes zoster, and recent studies have suggested that the incidence of herpes zoster recurrences is more frequent than previously reported, typically greater than 6%.2,3 moreover, it is reported that immunocompetent patients often experience more than two to three recurrent episodes, particularly in the same dermatome.2,3 however, the plausibility of recurrent herpes zoster has also been debated, with many clinicians hypothesizing that recurrent zoster in immunocompetent patients is often a abstract purpose: to determine the true etiology of cases of putative recurrent shingles referred to a dermatology clinic. methods: a prospective cohort study of patients aged 15-87 years with reported recurrent herpes zoster was conducted. vesicular fluid and serology for herpes simplex 1, 2, and varicella zoster virus immunoglobulins were obtained from patients presenting with vesicles. biopsies were obtained from patients with ambiguous presentations. results: 44 patients (56%) had evidence of herpes simplex virus infection. 32% of patients had positive herpes simplex virus cultures or polymerase chain reaction sequencing, and 24% additional patients were diagnosed with presumptive simplex infection based on elevated antibody titers. 44% of patients had a diagnosis other than zoster or simplex. one individual had a positive viral culture for varicella zoster virus. 99% of patients who presented with suspected recurrent herpes zoster had no definitive evidence of varicella zoster virus reactivation. conclusions: the most common diagnosis was herpes simplex infection. our results suggest that true recurrent shingles in immunocompetent patients is rare. introduction skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 8 misdiagnosis.4-8 the purpose of this study was to determine the etiology of cutaneous eruptions that have been previously diagnosed as “recurrent shingles”. we performed a prospective cohort analysis of 78 patients who were referred to a community outpatient dermatology clinic with “recurrent shingles”. irb approval was not needed as all patients received the standard of care. inclusion criteria consisted of a unilateral zosteriform rash, reported recurrence at same anatomical site, and/or recurring pain/discomfort at the same anatomical site. immunosuppression from illness and/or use of immunosuppressive agents were considered exclusionary. vesicular fluid was collected for varicella zoster virus / herpes simplex virus 1 and 2 viral culture or polymerase chain reaction (pcr) analysis. for lesions without vesicles or in the absence of primary morphology, herpes simplex-1 and -2 igg specific antibody assays were obtained. results were considered positive if igg titers were elevated. for clinically ambiguous presentations, skin biopsies were performed. subjects were between 15 and 87 years of age; the average age was 54 years with a standard deviation of 19.4. 77% of patients were female (n=60). 32% of patients presenting with recurrent herpes zoster had positive herpes simplex virus cultures or pcr, and 24% additional patients were diagnosed with presumptive simplex infection based on elevated antibody titers. 44% of patients had a diagnosis other than zoster or simplex. one individual had a positive viral culture for varicella zoster. 99% of patients who presented with suspected recurrent herpes zoster had no definitive evidence of varicella zoster virus reactivation. 43 patients (56%) had evidence of herpes simplex virus infection (table 1). our results suggest that true recurrent shingles in immunocompetent patients is rare, as only 1 out of 78 patients had definitive evidence of latent varicella zoster virus reactivation. while population-based studies suggesting that recurrences are common utilize a larger sample size2,3, their results are confounded by the inclusion of immunocompromised patients and the lack of sufficient laboratory or supporting data. to date, there has only been one large published report of laboratory-confirmed recurrences in immunocompetent patients over age 60: a herpes zoster vaccine study found that in a total of 1646 cases of established herpes zoster, only 5 were deemed recurrences.9 in immunocompetent patients, recurrent episodes occur in 1% to 6% of cases.10-13 our results emphasize the importance of diagnostic validity in classifying cases as true recurrent shingles. in our study, the most common diagnosis was herpes simplex infection (57%). herpes simplex virus 2 was attributed to most cases involving the buttocks while herpes simplex virus 1 was most frequently isolated on lesions presenting on the face (table 2). these anatomical distributions correspond to the sites of latency of herpes simplex virus 1 and herpes simplex virus 2 infection in the first and second divisions of the trigeminal ganglion and in the sacral sensory ganglia, respectively.14 furthermore, the average rate of recurrences reported by patients (monthly for sacral/ herpes methods results discussion skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 9 table 1. final diagnoses and characteristics of patients presenting with putative recurrent herpes zoster. number (n = 78) percentage final diagnosis herpes simplex eruption 44 56% post-herpetic neuralgia (phn) 14 19% phn + dermatitis 6 8% folliculitis 4 5% actinic keratosis 2 3% contact dermatitis 2 3% herpes zoster 1 1% excoriated ulcer 1 1% prurigo nodularis 1 1% fixed drug eruption 1 1% arthropod assault 1 1% anatomic distribution head/neck 19 26% chest/abdomen/back 19 24% anogenital (including buttocks) 30 38% extremities (including posterior thigh) 9 11% multiple sites 1 1% sex male 18 23% female 60 77% simplex virus 2 eruptions) and (every 3-4 months for trigeminal/ herpes simplex virus 1 eruptions) are consistent with rates of recurrent simplex infection14, suggesting that more recurrences of vesicles suggest a much greater possibility of herpes simplex virus. zosteriform herpes simplex virus infections are encountered in up to 25% of the cases initially diagnosed as herpes zoster on a clinical base, particularly in the facial dermatomes.15-19 these eruptions occur in both primary and recurrent infections, and are observed in patients of all ages.15-19 in addition, well-characterized manifestations of herpes simplex infections including herpes gladiatorum (n=2) and genital herpes (n=2) were also referred to our clinic as presumed recurrent shingles (table 2). women have “recurrent shingles” due to herpes simplex virus far more frequently than do men; this is particularly true of recurrent vesicles of the buttocks (figures 1 and 2), and for reasons unknown. herpes simplex virus reactivation is triggered by a variety of factors, including stress, uvirradiation, or immunosuppression, along with menstruation and changes in female sex hormones. however, this does not appear to be sufficient to trigger varicella zoster virus reactivation.20 post-herpetic neuralgia was implicated in many cases of “recurrent shingles” and can be characterized further as post-herpetic neuralgia with overlying unrelated skin conditions and post-herpetic neuralgia without cutaneous manifestations (table 1). post herpetic neuralgia was diagnosed in 14 patients (19%) who presented with unilateral recurrent intense pain or pruritus at a site of previous shingles and had no clear clinical or diagnostic abnormalities. post-herpetic neuralgia is the most common complication of herpes zoster, and a significant cause of morbidity.9-11 recognition of post-herpetic neuralgia allows for treatment to be tailored towards analgesic relief. overlying skin conditions included folliculitis, actinic keratosis, prurigo nodularis, contact dermatitis, fixed drug eruption, and arthropod assault. in addition, histopathology revealed a variety of nonspecific inflammatory patterns (spongiotic, interface, perifollicular, and perivascular dermatitis). a variety of conditions are known to mimic the skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 10 table 2. characteristics of herpes simplex infection. gender method of detection location average recurrence rate hsv-1 male: 3 female: 8 pcr/viral culture: 4 serology: 7 trigeminal: 4 abdomen: 1 buttocks: 2 thoracic: 1 suprapubic: 1 herpes gladiatorum: 2 every 3-4 months hsv-2 male: 5 female: 28 pcr/viral culture: 17 serology: 16 buttocks: 22 posterior thigh: 5 thoracic: 3 trigeminal: 1 genital herpes: 2 every 30 days figure 1. recurrent vesicular eruption on the buttock of a female patient figure 2. recurrent vesicular eruption on the buttock of a female patient appearance and distribution of herpes zoster, including staphylococcal skin infections21, impetigo22, 23 bullous lesions24, and lichen planus25. such entities may be attributed to wolf’s isotopic response, which describes the phenomenon of a cutaneous eruption that develops at the site of a healed, unrelated skin disease most commonly herpes zoster. recognition of this phenomenon allows the clinician to treat the primary illness. determining the etiology of the “recurrent shingles” has public health implications given the transmissibility of herpes simplex virus in comparison to varicella zoster virus. approximately 12% of patients aged 14-49 are herpes simplex virus 2 seropositive and 48% are herpes simplex virus 1 seropositive.26 in comparison, 99% of adults are varicella zoster virus seropositive due to natural infection with wildtype chickenpox or vaccination. therefore, a person with “recurrent shingles” due to herpes simplex virus may unknowingly transmit the infection. a limitation of this study is that it cannot establish with certainty a causal relationship between the patient presentation and hsv titers with igg alone; only a presumptive diagnosis of hsv infection can be made based on serology, which indicates past exposure or recent shedding. many patients skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 11 who are seropositive for herpes simplex virus, especially type 2, were unaware of their symptoms or had subclinical infection and were unlikely to present for culture or pcr analysis. in this study, laboratory evidence substantiated the clinical observation that the most common sites of suspected recurrent herpes zoster correlate with sites where herpes simplex virus 1 and 2 infections typically present, on orolabial and anogenital skin, respectively. differentiating between zoster and simplex is critical in reducing transmission of infection. postherpetic neuralgia, including cases with superimposed unrelated cutaneous manifestations, was also commonly misdiagnosed as recurrent shingles. our results support that herpes simplex virus commonly recurs but recurrence of zoster in immunocompetent individuals is rare. conflict of interest disclosures: none funding: none corresponding author: stephen k. tyring, md, phd, mba 1401 binz, suite 200 houston, tx 77004 phone: 713-528-8818 email: styring@ccstexas.com references: 1. gnann jw jr, whitley rj. herpes zoster. n engl j med 2002;347:340-346 2. yawn bp, wollan pc, kurland mg et al. herpes zoster recurrences more frequent than previously reported. mayo clin proc. 2011;86(2):88-93. 3. nakamura y, miyagawa f, okazaki a, et al. clinical and immunologic features of recurrent herpes zoster (hz). j am acad dermatol. 2016 nov;75(5):950-956.e1 4. chien aj. why do so many clinicians believe that recurrent zoster is common? derm online j. 2007; 13 (2):2. 5. volpo a, gatti a, pica f. frequency of herpes zoster recurrence. mayo clin proc. 2011;86(2):584-587. 6. pierson jc. reluctance regarding recurrent herpes zoster j am acad derm. 2017 apr;76(4):e143. 7. sax p. common curbsides: the patient with “recurrent zoster”. december 30, 2014. n engl j med journal watch. accessed 12 january 2019. https://blogs.jwatch.org/hiv-idobservations/index.php/common-curbsides-thepatient-with-recurrent-zoster/2014/12/30/ 8. heskel ns, hanifin jm. "recurrent herpes zoster": an unproved entity? j am acad dermatol. 1984 mar;10(3):486-90. 9. oxman mn, levin mj, johnson gr, et al. a vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. n engl j med, 352 (2005), pp. 2271-2284 10. hope-simpson r. the nature of herpes zoster: a long-term study and a new hypothesis. proc r soc med. 1965;58:9-20. 11. ragozzino mw, melton lj iii, kurland lt, chu cp, perry ho. population-based study of herpes zoster and its sequelae. medicine (baltimore, md). 1982;61:310-316. 12. hernandez, p.o., s. javed, n. mendoza, w. lapolla, l.d. hicks and s.k. tyring. family history and herpes zoster risk in the era of shingles vaccination. j clin virol. 52:344-348; 2011. 13. hicks, l.d., r.h. cook-norris, n. mendoza, v. madkan, a. arora, s.k. tyring. family history as a risk factor for herpes zoster: a case-control study. arch dermatol. 144: 603-608; 2008. 14. lafferty we, coombs rw, benedetti j, et al. recurrences after oral and genital herpes simplex virus infection. n engl j med 1987; 316:1444–9. 15. forrest wm, kaufman he (1976) zosteriform herpes simplex. am j ophthalmol 81: 86-88. 16. kalman cm, laskin ol (1986) herpes zoster and zosteriform herpes simplex virus infections in immunocompetent adults. am j med 81: 775778. [crossref] 17. rübben a, baron jm, grussendorf-conen ei (1997) routine detection of herpes simplex virus and varicella zoster virus by polymerase chain reaction reveals that initial herpes zoster is frequently misdiagnosed as herpes simplex. br j dermatol 137: 259-261. 18. koh mj, seah pp, teo ry (2008) zosteriform herpes simplex. singapore med j 49: e59-60. conclusion https://blogs.jwatch.org/hiv-id-observations/index.php/common-curbsides-the-patient-with-recurrent-zoster/2014/12/30/ https://blogs.jwatch.org/hiv-id-observations/index.php/common-curbsides-the-patient-with-recurrent-zoster/2014/12/30/ https://blogs.jwatch.org/hiv-id-observations/index.php/common-curbsides-the-patient-with-recurrent-zoster/2014/12/30/ http://www.ncbi.nlm.nih.gov/pubmed/3022586 http://www.ncbi.nlm.nih.gov/pubmed/18301829 skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 12 19. aithal s, kuruvila s, ganguly s (2013) zosteriform herpes simplex and herpes zoster: a clinical clue. indian dermatol online j 4: 369. 20. freeman ml, sheridan bs, bonneau rh, hendricks rl: psychological stress compromises cd8+ t cell control of latent herpes simplex virus type 1 infections. j immunol. 2007, 179: 322-32 21. schepp ed, cohen pr. zosteriform staphylococcus aureus cutaneous infection: report of two patients with dermatomal bacterial infection. skinmed. 2015;13:275–281. 22. cohen pr. zosteriform impetigo: wolf's isotopic response in a cutaneous immunocompromised district. dermatol pract concept. 2015 jul 31;5(3):35-9. 23. shetty s, rao r, pai s. impetigo contagiosa in a zosteriform pattern. j paediatr child health. 2016 jun;52(6):684-5. 24. chen sx, cohen pr. edema bullae mimicking disseminated herpes zoster. cureus. 2017 oct; 9(10): e1780 25. braun rp, barua d, masouyé i (1998) zosteriform lichen planus after herpes zoster. dermatology 197: 87-88. 26. mcquillan g, kruszon-moran d, flagg ew, and paulose-ram r. prevalence of herpes simplex virus type 1 and type 2 in persons aged 14–49: united states, 2015–2016. nchs data brief. 2018 feb. no. 304. https://www-ncbi-nlm-nih-gov.ezproxy.ttuhsc.edu/pubmed/26336623 poster presented at the 38th annual fall clinical dermatology conference; oct 17-20, 2019; las vegas, nv lebrikizumab, a high-affinity il-13 inhibitor, improves clinical manifestations in moderate-to-severe atopic dermatitis: primary results from a randomized, double-blinded, placebo-controlled, dose-ranging, phase 2b study e. guttman-yassky,1 a. blauvelt,2 l. f. eichenfield,3 a. paller,4 a. armstrong,5 j. drew,6 r. gopalan,6 e. simpson7 1icahn school of medicine at mount sinai, new york, ny; 2oregon medical research center, portland, or; 3university of california and rady children’s hospital, san diego, ca; 4northwestern university feinberg school of medicine, chicago, il; 5keck school of medicine at university of southern california, los angeles, ca; 6dermira, inc., menlo park, ca; 7oregon health and science university, portland, or introduction • moderate-to-severe atopic dermatitis (ad) is a prevalent, debilitating condition characterized by a broad range of clinical manifestations, including skin lesions and intense, persistent pruritus that can have a significant, multi-dimensional impact on quality of life1,2 • interleukin (il)-13 is a central pathogenic mediator driving multiple features of ad pathophysiology underlying the range of clinical manifestations3-5 • lebrikizumab (leb) is a novel, high-affinity monoclonal antibody targeting il-13 that selectively prevents formation of the il-13rα1/il4rα heterodimer receptor signaling complex while leaving endogenous regulation of il-13 intact objective • to report the efficacy and safety of leb from a randomized, double-blinded, placebo-controlled, dose-ranging, phase 2b study in adults with moderate-to-severe ad (nct03443024) methods study design • this phase 2b study consisted of a 16-week treatment period with 16-week safety follow-up (figure 1) • patients were randomized 3:3:3:2 to subcutaneous leb 125 mg every 4 weeks (q4w; 250 mg loading dose [ld]), 250 mg q4w (500 mg ld), 250 mg every 2 weeks (q2w; 500 mg ld at weeks 0 and 2), or placebo q2w for 16 weeks • patients requiring rescue therapy were allowed to use topical corticosteroids (tcs) for as brief a period as possible and could remain in the study; those requiring systemic rescue therapy were discontinued figure 1. study design week 0 week 4 week 8 week 12 week 16 week 32 placebo q2w (n=52) leb 250 mg q2w (n=75) 500 mg ld wk 0 & 2 leb 250 mg q4w (n=80) 500 mg ld wk 0 leb 125 mg q4w (n=73) 250 mg ld wk 0 safety follow-up to week 32 screening (≤30 days) randomized, double-blind treatmenta primary endpoint: percent change in easi from baseline at week 16 3:3:3:2 randomization n=280 apatients were seen every two weeks and received all study drug injections in the clinic easi, eczema area and severity index; ld, loading dose; q2w, every 2 weeks; q4w, every 4 weeks; wk, week study patients • eligible patients were ≥18 years, with eczema area severity index (easi) ≥16, investigator’s global assessment (iga) score ≥3 (5-point scale), ≥10% body surface area (bsa) affected, and chronic ad for ≥1 year for which topical treatment provided inadequate control or was medically inadvisable • patients were excluded for having had treatment with tcs or topical calcineurin inhibitors (tci) within 1 week prior to baseline • prior biologics were allowed if washout occurred as follows relative to baseline: dupilumab within 3 months, cell-depleting (eg, rituximab) within 6 months, other biologics within 5 half-lives or 16 weeks, and investigational drug within 8 weeks or 5 half-lives efficacy and safety assessments • the primary endpoint was percent change in easi from baseline at week 16 • secondary endpoints included proportion of patients achieving easi50, easi75, easi90, iga score of 0 or 1 (iga 0/1), pruritus numeric rating scale (nrs; 11-point scale [0 to 10]) change ≥4 points, and percent change in pruritus nrs from baseline at week 16 • visits occurred biweekly through week 16, and at weeks 20 and 24; a safety follow-up visit occurred at week 24, with telephone follow-up at week 32; safety assessments included treatment-emergent adverse events (teaes) statistical analyses • efficacy analyses used the modified intent-to-treat (mitt) population (all patients who were randomized and received study drug) • safety analyses used the safety population (those randomized who received ≥1 dose of study drug) • missing data through week 16 were imputed using markov chain monte carlo (mcmc) multiple imputation, with no imputation for missing pruritus data (prespecified) – data for patients requiring topical rescue were included if available; data for those requiring systemic rescue were considered missing from the time of withdrawal – a post hoc analysis was performed for pruritus, whereby missing data were imputed using mcmc imputation • statistical comparisons were performed between leb and placebo (and not between leb groups) results • a total of 73, 80, 75, and 52 patients were randomized to leb 125 mg q4w, 250 mg q4w, 250 mg q2w, and placebo, respectively • week 16 completion rates were similar across all leb groups and greater than placebo (figure 2) figure 2. patient disposition screened n=424 randomized n=280 placebo q2w n=52 n=23 (44.2%) discontinued 29 adverse event 1 lost to follow-up 4 pregnancy 1 protocol deviation 2 withdrawal by patient 20 physician decision 1 other 0 leb 125 mg q4w n=73 n=58 (79.5%) discontinued 15 adverse event 2 lost to follow-up 6 pregnancy 0 protocol deviation 0 withdrawal by patient 6 physician decision 0 other 1 leb 250 mg q4w n=80 n=62 (77.5%) discontinued 18 adverse event 3 lost to follow-up 5 pregnancy 0 protocol deviation 0 withdrawal by patient 7 physician decision 2 other 1 leb 250 mg q2w n=75 n=58 (77.3%) discontinued 17 adverse event 3 lost to follow-up 6 pregnancy 0 protocol deviation 0 withdrawal by patient 8 physician decision 0 other 0 completed week 16 percentages are based on the number of randomized subjects; one patient who was randomized in error was not included in the figure q2w, every 2 weeks; q4w, every 4 weeks • patient demographics and baseline disease characteristics were well matched across groups (table 1) • table 1. baseline demographics and disease characteristics (mitt population) placebo q2w n=52 leb 125 mg q4w n=73 leb 250 mg q4w n=80 leb 250 mg q2w n=75 baseline demographics age, mean (sd), years 42.2 (18.2) 36.7 (16.5) 40.2 (17.9) 38.9 (17.4) male, no. (%) 28 (53.8) 27 (37.0) 33 (41.3) 26 (34.7) race, no. (%) white 26 (50.0) 37 (50.7) 42 (52.5) 40 (53.3) black or african american 16 (30.8) 26 (35.6) 28 (35.0) 23 (30.7) american indian or alaska native 0 1 (1.4) 1 (1.3) 1 (1.3) asian 6 (11.5) 8 (11.0) 7 (8.8) 6 (8.0) multiple/other 4 (7.7) 1 (1.4) 2 (2.5) 5 (6.7) body mass index, mean (sd), kg/m2 29.7 (8.0) 30.1 (7.7) 29.2 (6.9) 28.1 (6.4) baseline disease characteristics disease duration, mean (sd), years 24.4 (17.4) 22.8 (15.4) 23.3 (16.7)b 22.1 (17.2) easi, mean (sd) 28.9 (11.8) 29.9 (13.5) 26.2 (10.1) 25.5 (11.2) iga, no. (%) 3, moderate 32 (61.5) 43 (58.9) 54 (67.5) 53 (70.7) 4, severe 20 (38.5) 30 (41.1) 26 (32.5) 22 (29.3) bsa involvement, mean (sd), percent 46.5 (22.7) 45.5 (24.5) 41.1 (20.9) 39.4 (21.5) pruritus nrs score,a mean (sd) 7.4 (2.4) 7.6 (2.0) 7.1 (2.4) 7.6 (1.9) aplacebo q2w, n=49; leb 125 mg q4w, n=68; leb 250 mg q4w, n=77; leb 250 mg q2w, n=69; bn=79 percentages are based on the number of patients in the modified intent-to-treat (mitt) population with a non-missing response bmi, body mass index; bsa, body surface area; easi, eczema area and severity index; iga, investigator’s global assessment (5-point scale); nrs, numeric rating scale; q2w, every 2 weeks; q4w, every 4 weeks; sd, standard deviation • rescue medication was infrequently required in leb-treated patients (leb 125 mg q4w: 12.3%; 250 mg q4w: 12.5%; 250 mg q2w: 13.3%; placebo: 34.6%) • topical medication was used by 28.8% of placeboversus 12.3%, 3.8%, and 8.0% of leb 125 mg q4w, 250 mg q4w, and 250 mg q2w-treated patients, respectively • mean duration of topical medication use was 8 days for placebo versus 4.9, 1.0, 2.5 days for leb 125 mg q4w, 250 mg q4w, and 250 mg q2w, respectively • these findings suggest that tcs use would not have confounded study results primary endpoint • all leb groups showed dose-dependent, statistically significant improvement in the primary endpoint versus placebo at week 16 (least squares mean percent change in easi: leb 125 mg q4w [-62.3%; p<0.05], 250 mg q4w [-69.2%, p<0.01], 250 mg q2w [-72.1%, p<0.001] versus placebo [ 41.1%]; (figure 3) figure 3. percent change in easi (mitt population) placebo q2w n=52 leb 125 mg q4w n=73 leb 250 mg q4w n=80 leb 250 mg q2w n=75 -41.1 -62.3 * -69.2 ** -72.1 *** 0 -20 -40 -60 -80 -100ls m ea n c ha ng e fr om b as el in e (% ) at week 16 (primary endpoint) 0 -20 -40 -60 -80 -100m ea n c ha ng e fr om b as el in e (% ) to week 16 4 8 12 160 placebo q2w (n=52) leb 125 mg q4w (n=73) leb 250 mg q4w (n=80) leb 250 mg q2w (n=75) a. b. -25.4 -31.3 -34.0 -40.6-42.4 -53.9 -62.5 -61.5* 0 -46.5 -61.2 -64.7 -69.7** -50.4 -64.1 -73.5 -72.8*** *p<0.05, **p<0.01, and ***p<0.001 versus placebo from least squares mean values and an analysis of covariance with a factor of treatment group and corresponding baseline easi score as a covariate; statistical comparison at week 16 only post-baseline up through week 16 visit summary statistics represent average values, obtained by averaging the summary statistics generated from each imputed dataset easi, eczema area and severity index; ls, least squares; q2w, every 2 weeks; q4w, every 4 weeks secondary endpoints • a greater proportion of lebversus placebo-treated patients achieved easi50, easi75, easi90, and iga 0/1 at week 16, with statistically significant improvements seen with leb 250 mg q2w and q4w (figure 4) figure 4. secondary endpoints to week 16 (mitt population) a. placebo q4w (n=52) leb 125 mg q4w (n=73) leb 250 mg q4w (n=80) leb 250 mg q2w (n=75) 0 20 40 60 80 100 0 4 8 12 p at ie nt s (% ) easi50 easi75 easi90 iga 0/1 16 week **77.0 b. 0 20 40 60 80 100 0 4 8 12 p at ie nt s (% ) 16 week c. 0 20 40 60 80 100 0 4 8 12 p at ie nt s (% ) 16 week d. 0 20 40 60 80 100 0 4 8 12 p at ie nt s (% ) 16 week 45.8 ***81.0 66.4 **56.1 24.3 ***60.6 43.3 48.3 16.6 66.9 43.8 7.6 0.5 14.2 3.7 26.0 4.0 29.8 17.3 28.4 5.2 36.4 20.5 24.0 4.8 31.3 14.7 29.9 3.4 42.2 22.1 10.0 0.1 13.9 3.1 38.5 16.7 45.5 30.8 23.4 2.7 30.4 16.7 74.2 34.9 83.1 68.7 68.7 34.8 69.6 57.8 45.2 26.8 52.6 41.9 **36.1 11.4 ***44.0 26.1 *33.7 15.3 **44.6 26.6 *p<0.05, **p<0.01, and ***p<0.001 versus placebo from pairwise cochran-mantel-haenszel tests post-baseline up through the week 16 visit summary statistics represent average values, obtained by averaging the summary statistics generated from each imputed dataset easi50/75/90, ≥50%/75%/90% improvement from baseline in eczema area and severity index; iga 0/1, score of 0 ‘clear’ or 1 ‘almost clear’ in investigator global assessment (5-point scale) from baseline; q2w, every 2 weeks; q4w, every 4 weeks patient-assessed pruritus • a greater proportion of lebversus placebo-treated patients achieved pruritus nrs change ≥4 points at week 16; dose-dependent, statistically significant improvement was also seen in lebversus placebo-treated patients for the least squares mean percent change in pruritus nrs from baseline (figure 5) figure 5. pruritus nrs at week 16 (mitt population) change ≥4 points percent change from baseline 27.3 0 20 40 60 80 100 p at ie nt s (% ) placebo q2w leb 125 mg q4w leb 250 mg q4w leb 250 mg q2w a. b. 22 39.3 52n: 41.8 55 43.5 73 47.4 57 46.2 80 70.0 50 67.2 75 no imputation (observed cases) mcmc imputation 4.3 -100 -60 -40 -20 0 20 ls m ea n c ha ng e fr om b as el in e (% ) placebo q2w leb 125 mg q4w leb 250 mg q4w leb 250 mg q2w 22 -4.6 52n: -35.9 55 -36.5 73 -49.6 56 -46.4 80 -60.6 50 -58.5 75 -80 no imputation (observed cases) mcmc imputation *** ** *** ** ** ** *** *** **p<0.01 and ***p<0.001 versus placebo; panel a: from pairwise cochran-mantel-haenszel tests; panel b: from an analysis of covariance with a factor of treatment group and corresponding baseline pruritus nrs as the covariate ls, least squares; mcmc, markov chain monte carlo; nrs, numeric rating scale; q2w, every 2 weeks; q4w, every 4 weeks • improvements in pruritus nrs were seen to week 16 (figure 6) figure 6. pruritus nrs to week 16 (mitt population; observed cases) -4.7 -29.6 -21.9 -25.2 -100 -40 -20 0 20 0 2 4 6 8 10 12 14 m ea n c ha ng e fr om b as el in e (% ) percent change from baselinechange ≥4 points 13.2 27.5 37.1 39.3 28.6 16.7 19.0 27.321.1 32.7 34.0 42.3 51.0 44.7 46.7 41.8 19.7 30.9 46.6 50.9 50.0 57.1 56.8 47.4 31.7 51.9 51.9 58.5 61.8 63.3 68.2 *** 70.0 0 20 40 60 80 100 0 2 4 6 8 10 12 14 16 p at ie nt s (% ) week week b.a. -80 -60 16 -25.4 -31.3 -34.4 -38.8 -27.7 -32.0 -45.0 -53.0 -21.7 -39.6 -48.6 -45.7 -22.4 -31.3 -44.5 -57.1 -13.3 -41.2 -50.9 -60.1 -15.8 -41.9 -52.3 -63.7 6.8 ** -36.9 ***-48.6 *** -61.8 placebo q2w leb 125 mg q4w leb 250 mg q4w leb 250 mg q2w placebo q2w leb 125 mg q4w leb 250 mg q4w leb 250 mg q2w **p<0.01 and ***p<0.001 versus placebo; panel a: from pairwise cochran-mantel-haenszel tests; panel b: from ls mean and an analysis of covariance with a factor of treatment group and corresponding baseline pruritus nrs as the covariate patient numbers fluctuate at each week as these are observed data ls, least squares; nrs, numeric rating scale; q2w, every 2 weeks; q4w, every 4 weeks • differences in the proportions of patients achieving pruritus nrs change ≥4 points were seen by day 2: 6.3%, 5.6%, 15.3% of leb 125 mg q4w, 250 mg q4w, 250 mg q2w versus 4.5% of placebo-treated patients, respectively safety • teaes were reported in 57.5%, 48.8%, 61.3% of leb 125 mg q4w, 250 mg q4w, 250 mg q2w versus 46.2% of placebo-treated patients, respectively (table 2); most were mild or moderate in severity and did not lead to discontinuation • rates of serious teaes were low in all treatment groups, and none were related to treatment • teaes reported in ≥5% in any leb group were upper respiratory tract infection, nasopharyngitis, fatigue, headache, and injection site pain • low rates of conjunctivitis were observed across doses: 1.4%, 3.8%, 2.7% of leb 125 mg q4w, 250 mg q4w, 250 mg q2w versus 0% of placebo-treated patients, respectively • a similar rate of herpes infections was reported in leb groups versus placebo: 2.7%, 5.0%, 2.7% of leb 125 mg q4w, 250 mg q4w, 250 mg q2w versus 3.8% of placebo-treated patients, respectively table 2. summary of treatment-emergent adverse events (safety population) placebo q2w n=52 leb 125 mg q4w n=73 leb 250 mg q4w n=80 leb 250 mg q2w n=75 patients reporting ≥1 teae, n (%) 24 (46.2) 42 (57.5) 39 (48.8) 46 (61.3) patients reporting ≥1 serious teae , n (%) 2 (3.8) 2 (2.7) 0 2 (2.7) number of serious teaes, no. 3 2 0 2 deaths, n (%) 0 0 0 0 patients who discontinued study due to teae, n (%) 1 (1.9) 2 (2.7) 4 (5.0) 3 (4.0) common teaes reported in ≥5% in any leb treatment group,a n (%) upper respiratory tract infection 3 (5.8) 6 (8.2) 9 (11.3) 2 (2.7) nasopharyngitis 2 (3.8) 4 (5.5) 2 (2.5) 9 (12.0) headache 3 (5.8) 3 (4.1) 1 (1.3) 4 (5.3) injection site pain 1 (1.9) 0 3 (3.8) 4 (5.3) fatigue 0 0 4 (5.0) 0 teaes of clinical interest, n (%) injection site reactionsb 1 (1.9) 2 (2.7) 4 (5.0) 7 (9.3) herpes viral infectionsc 2 (3.8) 2 (2.7) 4 (5.0) 2 (2.7) conjunctivitisd 0 1 (1.4) 3 (3.8) 2 (2.7) ameddra version 20.1 preferred terms; bincludes meddra preferred terms for injection site-related aes, including injection site pain, erythema, pruritus, edema, swelling, rash, dermatitis, infection, and reaction; cincludes meddra preferred terms oral herpes, herpes zoster, genital herpes, herpes simplex, and eczema herpeticum; dincludes meddra preferred terms conjunctivitis, conjunctivitis bacterial, and conjunctivitis allergic teaes are those with an onset on or after the date of first study drug injection; patients may have reported ≥1 preferred term q2w, every 2 weeks; q4w, every 4 weeks; teae, treatment-emergent adverse event conclusions • in this phase 2b, placebo-controlled study, all leb groups showed dose-dependent and statistically significant improvement in the primary endpoint (percent change in easi from baseline at week 16) • leb demonstrated a dose-dependent response across all endpoints measured, with marked improvement at both 250 mg q2w and q4w doses; for skin symptoms, an effect was seen at week 4 • effects on itch were observed as early as day 2 in patients who received a 500 mg loading dose at day 0 • leb was well tolerated, and consistent with previous studies, teae rates were low; across all leb ad studies,6 conjunctivitis has been reported at low rates similar to those in patients receiving placebo • these data highlight that selective blockade of il-13 with leb leads to improvements in key ad clinical severity scores and pruritus while maintaining a favorable safety profile references 1. bieber t. ann dermatol. 2010;22(2):125-37. 2. drucker am, wang ar, li wq, et al. j invest dermatol. 2017;137(1):26-30. 3. moyle m, cevikbas f, harden jl, guttman-yassky e. exp dermatol. 2019;28(7):756-68. 4. bieber t. allergy. 2019. [epub ehead of print] 5. tsoi lc, rodriguez e, degenhardt f, et al. j invest dermatol. 2019; 139(7):1480-89. 6. simpson el, flohr c, eichenfield lf, et al. j am acad dermatol. 2018;78(5):863-71. acknowledgements this study was funded by dermira, inc. medical writing support was provided by prescott medical communications group (chicago, il). all costs associated with development of this poster were funded by dermira, inc. author disclosures egy: employee of mount sinai and has received research funds (grants paid to the institution) from abbvie, almirall, amgen, anaptysbio, asana biosciences, boerhinger-ingelhiem, celgene, dermavant, ds biopharma, eli lilly, glenmark, galderma, innovaderm, janssen, kiniska, kyowa kirin, leo pharma, novan, pfizer, ralexar, regeneron, sienna biopharma, ucb, and union therapeutics. consultant for egy is also a consultant for abbvie, almirall, amgen, asana biosciences, boerhinger-ingelhiem, cara therapeutics, celgene, concert, dbv, dermira, ds biopharma, eli lilly, emd serono, escalier, galderma, glenmark, kyowa kirin, leo pharma, mitsubishi tanabe, pfizer, rapt therapeutics, regeneron, sanofi, sienna biopharma, and union therapeutics. ab: scientific adviser and/or clinical study investigator for abbvie, aclaris, akros, allergan, almirall, amgen, arena, athenex, boehringer ingelheim, bristol-myers squibb, celgene, dermavant, dermira, eli lilly and company, flx bio, galderma, genentech/roche, glaxosmithkline, janssen, leo, meiji, merck sharp & dohme, novartis, pfizer, purdue pharma, regeneron, revance, sandoz, sanofi genzyme, sienna pharmaceuticals, sun pharma, ucb pharma, valeant, and vidac. paid speaker for abbvie, regeneron, and sanofi genzyme. lfe: scientific adviser and/or clinical study investigator for abbvie, allergan, almirall, amgen, asana, dermavant, dermira, ds biopharma, eli lilly, forte, galderma, glenmark, incyte, leo, matrisys, novartis, pfizer ortho dermatologics/valeant, regeneron, sanofi genzyme, ucb pharma. ap: investigator for abbvie, anaptysbio, eli lilly, galderma, incyte, leo, novartis, sanofi and regeneron. consultant for abbvie, asana, dermavant, dermira, galderma, eli lilly, forte, leo, menlo, novartis, pfizer, regeneron, and sanofi. aa: research, investigator, and/or consultant for abbvie, bristol-myers squibb, dermavant, dermira, janssen, khk, leo, lilly, novartis, ortho dermatologics, regeneron, sanofi, and ucb. jd, rg: employee of dermira. es: reports personal fees from abbvie, anacor, boehringer-ingelheim, dermavant, eli lilly, forte bio, incyte, leo pharmaceutical, medimmune, menlo therapeutics, pfizer, pierre fabre dermo cosmetique, regeneron, roivant, sanofi, and valeant. reports grants from abbvie, amgen, celgene, chugai, eli lilly, galderma, genentech, kyowa hakko kirin, leo pharmaceuticals, medimmune, merck, novartis, pfizer, regeneron, sanofi, tioga, and vanda. powerpoint presentation 3 years of tralokinumab treatment provides long-term disease control as demonstrated by clinically meaningful outcomes in moderate-to-severe atopic dermatitis richard b warren1, kristian reich2, eric simpson3, richard langley4, antonio costanzo5, hidehisa saeki6, peter almgren7, emilia vacko7, anna carlsson7, melinda gooderham8, mette deleuran9, juan francisco silvestre10, stefan weidinger11, andrew blauvelt12 1dermatology centre, salford royal nhs foundation trust and nihr biomedical research centre, the university of manchester, manchester, uk; 2translational research in inflammatory skin diseases, institute for health services research in dermatology and nursing, university medical center hamburg-eppendorf, hamburg, germany; 3department of dermatology, oregon health & science university, portland, or, usa; 4division of clinical dermatology and cutaneous science, dalhousie university, halifax, nova scotia, canada; 5dermatology unit department of biomedical sciences, humanitas university, milano, italy; skin pathology laboratory, humanitas research hospital irccs, milano, italy; 6department of dermatology, nippon medical school, tokyo, japan; 7leo pharma a/s, ballerup, denmark; 8skin centre for dermatology, peterborough, on, canada; department of dermatology, queen's university, kingston, on, canada; probity medical research, waterloo, on, canada; 9department of dermatology, aarhus university hospital, aarhus, denmark; 10dermatology department, hospital general universitario de alicante, alicante, spain; 11department of dermatology and allergy, university hospital schleswig-holstein, campus kiel, kiel, germany; 12oregon medical research center, portland, or, usa ecztend interim efficacy analysis set n=347 age median years (iqr) 42.0 (30.0; 53.0) sex n (%) male female 205 (59.1) 142 (40.9) race n (%)a white black asian 259 (74.6) 20 (5.8) 56 (16.1) parent trial n (%) ecztra 1 ecztra 2 224 (64.6) 123 (35.4) age at onset of ad median years (iqr) 3.0 (1.0; 15.0) duration of ad median years (iqr) 29.0 (19.0; 43.0) parent trial baseline ecztend baseline iga severity n (%) clear/minimal (score=0/1) mild (score=2) moderate (score=3) severe (score=4) 172 (49.6) 175 (50.4) 98 (28.2) 123 (35.4) 106 (30.5) 20 (5.8) easi median (iqr) 26.7 (19.7; 38.4) 4.7 (2.2; 12.4) scorad median (iqr) 68.1 (60.8; 78.1) 32.8 (20.6; 46.9) dlqi median (iqr), n 17.0 (11.0; 23.0), n=343 5.0 (2.0; 10.0), n=332 worst weekly pruritus nrsa median (iqr), n 7.9 (6.9; 8.9), n=346 5.0 (3.0; 8.0), n=347 table 1. baseline demographic and disease characteristics of patients with 3 years total tralokinumab treatment (ecztend interim efficacy analysis set) table 2. summary of adverse events (aes) in patients with 3 years total tralokinumab treatment ain pts, worst pruritus nrs was assessed daily; in ecztend, worst pruritus nrs was assessed based on recall of the previous week before the visit. conclusions • clinically meaningful improvements were observed in ad signs and symptoms in patients with moderate-to-severe ad treated with tralokinumab for 3 years • nine out of ten patients achieved at least one of the clinically relevant outcomes of easi ≤ 7, itch nrs ≤ 4, or dlqi ≤ 5, representing mild/no ad; approximately 60% achieved clinically meaningful outcomes by all three measures • the response rates were maintained over time with patients having easi ≤ 7 for more than 80% of visits during the 3 years of treatment • these data, in combination with the favorable safety profile, suggest tralokinumab as an efficacious and well-tolerated treatment option for long-term disease control in patients with moderate-tosevere ad aincludes 347 patients from the pts ecztra 1 and 2 who had consistently received tralokinumab for a total of 3 years at data cutoff, april 30, 2021. bincludes patients from a pooled safety analysis set from parent trials ecztra 1, 2, 3, 5, and phase 2b, previously presented at rad virtual 20201; aes related to study drug and aes leading to withdrawal during initial treatment sourced from data on file; tcs rules varied across parent trials with mandatory tcs in ecztra 3, and tcs use not part of treatment regimen in ecztra 1, ecztra 2, and ecztra 5. crate calculated by number of patients divided by pye until first event, multiplied by 100. drate calculated by number of events divided by pye, multiplied by 100. efor pts, cochran-mantel-haenszel weights were applied to calculate adjusted ae incidences and rates to account for different randomization ratios across pts.7 faes related to study drug comprise aes considered possibly or probably related by the investigator and aes with missing causality. objective to evaluate the efficacy and safety of 3 years of tralokinumab treatment, using clinically relevant outcomes indicating disease control, for adults with moderate-to-severe ad materials and methods patients and treatment • in ecztend, patients who completed pt of tralokinumab received open-label tralokinumab 300 mg every two weeks (q2w, home use) plus optional topical corticosteroids (tcs, us class ≥4 or europe class ≤3) or topical calcineurin inhibitor (tci), with visits every 8 weeks o for key inclusion and exclusion criteria, please see blauvelt et al5 o multiple tralokinumab pt of varying duration will contribute to the ecztend population (ecztra 1-8 and the investigator-initiated study traski, conducted in 11 countries) o while ecztra 3-5 and 7 were completed at data cutoff (april 30, 2021), participants in these trials did not receive 52 weeks of tralokinumab and therefore were not included in the 3-year efficacy analysis set • this post hoc analysis assessed tralokinumab efficacy in a homogenous group of participants with the longest tralokinumab treatment duration at data cutoff (april 30, 2021) o data are presented from eligible adult patients with moderate-to-severe ad who completed 3 years of tralokinumab treatment irrespective of response in the pt ecztra 1 and 2 (1 year in pt, 2 years in ecztend; figure 1; n=347 of 1442 total enrolled in ecztend at data cutoff) analyses • efficacy outcomes assessed were: o proportion of patients with 3 years total tralokinumab treatment achieving easi-75/90, iga 0/1, and easi ≤ 7 o percentage of patients achieving mild or no disease, defined as easi ≤ 7, itch nrs ≤ 4, or dlqi ≤ 5, after 3 years of tralokinumab treatment o proportion of time with mild/no disease during 3 years total tralokinumab treatment • for easi-75/90 and iga 0/1 response rates, as observed data are presented, and intermittent missing data are presented using last observation carried forward (locf). modified non-responder imputation (mnri) sets discontinuation from ecztend due to adverse event(s) or lack of efficacy as non-response and uses locf for other missing data results baseline demographics and characteristics • this post hoc analysis included 347 patients from the pts ecztra 1 and 2 who had entered ecztend and consistently received tralokinumab for a total of 3 years at data cutoff, april 30, 2021 (fig. 1b, table 1) • amongst patients who completed 3 years of tralokinumab treatment (n=347), median easi improved from 26.7 (iqr 19.7; 38.4) at pt baseline to 3.0 (iqr 1.0; 6.7) after one year of pt sustained improvement in lesion extent and severity with continued tralokinumab • amongst patients who completed 3 years of tralokinumab treatment at data cutoff, o easi-75 and easi-90 were achieved in 76% (263/347) and 54% (186/347) of patients by mnri, respectively (figure 2) o iga 0/1 was achieved in 44% (151/347) by mnri (figure 2) o easi ≤7 was achieved by 75% (261/347) by mnri (figure 2) figure 2. proportion of patients with 3 years total tralokinumab treatment achieving easi-75, easi-90, iga 0/1, and easi ≤7 aas observed, includes patients from the pts ecztra 1 and 2 who had consistently received tralokinumab for a total of 3 years at data cutoff, april 30, 2021. bintermittent missing data imputed using locf. cdiscontinuation from ecztend due to adverse event(s) or lack of efficacy set as non-response, other missing imputed with locf. scan to download a copy of this poster copies of this poster and its content, obtained through this qr code, are for personal use only and may not be reproduced without written permission from the authors introduction • atopic dermatitis (ad) is a chronic skin disease which may impact patients throughout their lifespan, requiring efficacious long-term treatment options with a favorable safety profile1 • the european guidelines (euroguiderm) define disease control or remission as satisfactory reduction of the signs and symptoms of ad whilst being on a safe long-term anti-inflammatory treatment2 o an international consensus previously defined a set of core decision points for systemic therapies at 6 months, including easi ≤ 7, itch nrs ≤ 4 and dlqi ≤ 5 representing mild/no disease3 • tralokinumab, a specific, high-affinity interleukin-13 inhibitor, is approved in europe, canada, and the united states for the treatment of adults with moderate-to-severe ad • ecztend (nct03587805) is an ongoing open-label extension trial assessing the safety and efficacy of tralokinumab over 5 years after the completion of parent trials (pt) o a recently presented interim safety analysis of adult patients with up to 42 months of exposure confirmed the safety profile of tralokinumab4 maintained improvements in clinically relevant outcomes at 3 years of tralokinumab treatment • patients were controlled (mild/no disease) for the majority of the 3 years of tralokinumab treatment (figure 3) • at 3 years of tralokinumab treatment, 93% (254/274, as observed) of patients achieved at least one outcome (figure 4) • median duration of response during pt and ecztend up to week 104, as observed: o >80% of visits with easi ≤ 7 response [84.7 (q1,q3; 55.8, 93.8)%] o >80% of visits with dlqi ≤ 5 [84.1 (43.1, 96.9)%] o >70% of visits with itch nrs ≤ 4 [73.8 (31.7, 91.3)%] • using mnri, 84% of patients achieved at least one clinically meaningful improvement, and 51% achieved clinically meaningful improvements of all three measures 93% (254/274) of patients achieved at least one outcome on tralokinumab figure 4. percentage of patients achieving mild or no disease by at least one outcome after 3 years of tralokinumab treatment 9% dlqi ≤5 n/n 206/270 12% 6% easi ≤7 n/n 227/274 itch nrs ≤4 n/n 188/273 3% 4% 3% 58% data as observed. denominator is the smallest number of patients with dlqi, easi, and itch nrs measurement(s) in category, except for individuals with no response where largest number is used. no response includes non-evaluable patients, e.g., for category dlqi≤5 + easi≤7 where dlqi is not measured for one or more patient(s). no new safety signals with continued tralokinumab treatment • the safety profile was consistent with the pts6 and the overall ecztend population (n=1442),4 with no new safety signals arising with continued tralokinumab (table 2) aes in ecztend ecztend interim efficacy analysis seta aes up to week 16 in parent trials initial tralokinumab treatmentb tralokinumab q2w + optional tcs (n=347; pye=707.7) tralokinumab q2w ± tcs (n=1605; pye=473.2) placebo q2w ± tcs (n=680; pye=193.1) n (%) ratec [(np/pye)*10 0] e rated [(ne/pye)*10 0] n (adj. %)d e adj. rated,e [(ne/pye)*10 0] n (adj. %)d e adj. rated,e [(ne/pye)*10 0] all aes 295 (85.0) 144.2 1422 200.9 1080 (65.7) 3148 639.5 449 (67.2) 1276 678.3 aes related to study drugf 102 (29.4) 18.3 251 35.5 463 (28.0) 1025 207.6 176 (26.8) 365 195.6 severity mild 247 (71.2) 80.5 917 129.6 881 (53.2) 2127 429.8 326 (49.0) 738 391.0 moderate 180 (51.9) 40.6 450 63.6 518 (31.5) 917 189.5 258 (39.0) 478 254.3 severe 31 (8.9) 4.6 55 7.8 77 (4.6) 104 20.2 40 (6.3) 60 33.0 serious aes 31 (8.9) 4.6 34 4.8 37 (2.1) 38 7.4 18 (2.8) 22 11.9 leading to withdrawal from trial 9 (2.6) 1.3 9 1.3 34 (2.0) 42 8.6 12 (1.8) 15 8.0 references 1. weidinger s, novak n. lancet. 2016;387(10023):1109-1122. 2. wollenberg a, et al. j eur acad dermatol venereol. 2022;36(9):1409-1431. 3. de bruin-weller m, et al. acta derm venereol 2021; 101: adv00402. 4. blauvelt a, et al. poster presented at: american academy of dermatology annual meeting; march 25-29, 2022, boston, ma. 5. blauvelt a, et al. j am acad dermatol. 2022;s0190-9622(22)02345-3. 6. simpson e, et al. poster presented at: revolutionizing atopic dermatitis (rad) conference; december 13–14, 2020, virtual. 7. chuang-stein c. pharm stat 2011; 10:3–7. disclosures richard b warren has received research grants or consulting fees from abbvie, almirall, amgen, arena, astellas, avillion, boehringer ingelheim, bristol myers squibb, celgene, dice, eli lilly, gsk, janssen, leo pharma, medac, novartis, pfizer, sanofi, sun pharma, ucb, and union. he is supported by the manchester nihr biomedical research centre. kristian reich has served as advisor and/or paid speaker for and/or participated in clinical trials sponsored by abbvie, almirall, amgen, boehringer ingelheim, bristol-myers squibb, celgene, forward pharma, gilead, galderma, janssen-cilag, kyowa kirin, leo, lilly, medac, novartis, ocean pharma, pfizer, sanofi, ucb. kristian reich is co-founder of moonlake immunotherapeutics. eric simpson reports grants and/or personal fees from abbvie, boehringer ingelheim, celgene, dermavant, dermira, eli lilly, fortébio, galderma, incyte, kyowa kirin, leo pharma, medimmune, menlo therapeutics, merck, novartis, ortho dermatologics, pfizer, pierre fabre dermo cosmetique, regeneron, sanofi, tioga, and valeant. richard langley has served and received compensation in the form of grants and/or honoraria as principal investigator for and is on the scientific advisory board or has served as a speaker for abbvie, amgen, boehringer ingelheim, celgene, eli lilly, janssen, leo pharma, merck, novartis, pfizer, and ucb. antonio costanzo has received research grants or consulting fees from abbvie, almirall, amgen, boehringer ingelheim, bristol myers squibb, celgene, eli lilly, janssen, leo pharma, novartis, pfizer, sanofi, ucb. hidehisa saeki has received lecture fees from kyorin, kyowa kirin, leo pharma, mitsubishi tanabe, maruho, sanofi, tokiwa, and taiho; and scholarship donations from esai, mitsubishi tanabe, maruho, and torii. peter almgren, emilia vacko, and anna carlsson are employees of leo pharma. melinda gooderham has been an investigator, speaker and/or advisor for: abbvie, amgen, akros, anaptysbio, aslan, arcutis, bausch health, bms, boehringer ingelheim, celgene, dermira, dermavant, eli lilly, galderma, gsk, incyte, janssen, kyowa kirin, leo pharma, medimmune, merck, novartis, pfizer, regeneron, roche, sanofi genzyme, sun pharma, and ucb. mette deleuran has received research support, honoraria for lecturing, and/or is on consulting/advisory board agreements with abbvie, arena pharmaceuticals, aslan pharmaceuticals, incyte, la roche posay, leo pharma, lilly, pfizer, pierre fabre, regeneron, and sanofi genzyme. juan francisco silvestre has served as a consultant and received speaking fees at educational events for sanofi-genzyme, regeneron, abbvie, leo pharma, and novartis and has served as the principal investigator in clinical trials sponsored by abbvie, amgen, astrazeneca, bms, galderma, incyte, leo pharma, lilly, novartis, and pfizer. stephan weidinger has received institutional research grants from sanofi deutschland gmbh, leo pharma, and la roche posay, has performed consultancies for sanofi-genzyme, regeneron, leo pharma, abbvie, pfizer, eli lilly, kymab, and almirall, he has also lectured at educational events sponsored by sanofi-genzyme, regeneron, leo pharma, abbvie, and eli lilly, and is involved in performing clinical trials with many pharmaceutical industries that manufacture drugs used for the treatment of psoriasis and atopic dermatitis. andrew blauvelt has served as a speaker, scientific adviser, and / or clinical study investigator for abbvie, abcentra, aligos, almirall, amgen, arcutis, arena, aslan, athenex, boehringer ingelheim, bristol-myers squibb, dermavant, ecor1, eli lilly, evommune, forte, galderma, incyte, janssen, landos, leo pharma, novartis, pfizer, rapt, regeneron, sanofi genzyme, sun pharma, ucb pharma, vibliome, and xencor acknowledgements this analysis was sponsored by leo pharma a/s. medical writing and editorial support from alphabet health by meredith whitaker, phd and juliel espinosa, phd was funded leo pharma a/s, ballerup, denmark, according to good publication practice guidelines (https://www.ismpp.org/gpp3). richard b warren is supported by the manchester nihr biomedical research centre. this work was previously presented at eadv 2022. abbreviations %, percentage of patients with ≥1 event; adj., adjusted (for pts, cochran-mantel-haenszel weights were applied to calculate adjusted ae incidences and rates to account for different randomization ratios across pts)7; ae, adverse event; ad, atopic dermatitis; bp, parent trial baseline; dlqi, dermatology life quality index; e, number of adverse events; easi, eczema area and severity index; iga, investigator’s global assessment; iqr, interquartile range; itch nrs, peak worst weekly itch nrs; locf, last observation carried forward; mnri, modified non-responder imputation; n, number of patients achieving the indicated metric, or with ≥1 event; ne, number of events; np, number of patients; n, number of patients with recorded observation; nrs, numerical rating scale; pye, patient-years of exposure; pt, parent trial; q2w, every 2 weeks; scorad, scoring atopic dermatitis; sd, standard deviation; tci, or topical calcineurin inhibitor; tcs, topical corticosteroids. limitations • the analysis presented here represents a subgroup of patients who were eligible, chose to enter from two of the pts and were treated for two years in ecztend by the time of data cutoff, and as such, the data may not be generalizable to the full tralokinumab population (see figure 1b). analyses on the full two-year cohort were previously presented4) in ecztend, worst itch nrs was assessed based on recall of the previous week before the visit figure 3. percent response from parent trial baseline in disease severity, itch, and life quality over 3 years figure 1. schematic of (a) ecztend interim analysis of patients previously treated with tralokinumab monotherapy for 52 weeks in ecztra 1 and 2, followed by 104 weeks of treatment in ecztend and (b) patient disposition at parent trial completion, ecztend baseline, and at april 30, 2021 data cutoff https://www.ismpp.org/gpp3 slide 1: 3 years of tralokinumab treatment provides long-term disease control as demonstrated by clinically meaningful outcomes in moderate-to-severe atopic dermatitis bms-986165, an oral, selective tyk2 inhibitor, in the treatment of moderate to severe psoriasis as assessed by the static physician’s global assessment (spga)/body surface area (bsa) composite tool (spga×bsa), a clinically useful alternative to pasi alice b. gottlieb,1 bruce strober,2 diamant thaçi,3 kenneth gordon,4 sudeep kundu,5 renata kisa,5 lan wei,5 subhashis banerjee,5 joseph f. merola6 1icahn school of medicine at mount sinai, new york, ny, usa; 2yale university, new haven, ct, and central connecticut dermatology research, cromwell, ct, usa; 3research institute and comprehensive center for inflammation medicine, university of lübeck, lübeck, germany; 4medical college of wisconsin, milwaukee, wi, usa; 5bristol-myers squibb company, princeton, nj, usa; 6harvard medical school, boston, ma, usa conclusions • the spga×bsa offers more information on the nature of a patient’s disease — ie, on plaque quality and severity as well as bsa — than either measure alone. cutoffs defining minimal disease activity for spga×bsa have been published13 • in patients with moderate to severe psoriasis treated with bms-986165 or placebo for 12 weeks, similar trends were observed for spga×bsa and pasi for all measures evaluated, including percentage mean change and percent improvement from baseline and the proportion of patients achieving spga×bsa 75 or pasi 75 • there was a strong correlation between spga×bsa and pasi score at week 12 for all bms-986165 treatment groups and placebo, and a moderate correlation was observed between spga×bsa and dlqi score • these data further support spga×bsa as a simple, accurate, and convenient alternative to pasi that can be used in both clinical trial and practice settings2–5 introduction • the psoriasis area and severity index (pasi), spga, and percentage of bsa involvement are all instruments for the assessment of disease activity in psoriasis, although each has limitations1,2 — pasi is a composite measure requiring a complex multistep formula that restricts its routine use in the clinic; the spga assesses erythema, desquamation, and induration of psoriatic plaques independent of the extent of bsa involved with the lesions, while the bsa does not assess the severity of psoriatic lesions1,2 • several studies have shown that measures that combine some form of investigator global assessment with bsa, such as the product of spga and bsa (spga×bsa), strongly correlate with pasi in the assessment of moderate to severe psoriasis2–5 • tyrosine kinase 2 (tyk2) activates intracellular signal transducer and activator of transcription (stat)dependent signaling pathways of specific cytokines, including interleukin (il)-23, il-12, and type i interferons, that are involved in the pathogenesis of psoriasis and other immune-mediated disorders6–10 • bms-986165 is an oral, selective tyk2 inhibitor with a unique mode of binding to the regulatory pseudokinase domain of the enzyme, which provides high functional selectivity for tyk2, rather than the active kinase domain targeted by other tyrosine kinase inhibitors7,11 • in a 12-week, phase 2 trial (nct02931838) in adults with moderate to severe plaque psoriasis, bms-986165 demonstrated a dose-dependent improvement in pasi 75 response and a favorable safety profile12 — at week 12, pasi 75 responses were highest (67–75%) at doses from 3 mg twice daily (bid) up to 12 mg once daily (qd) versus placebo (7%; p<0.001; primary endpoint) objective • this post hoc analysis of the phase 2 trial evaluated the composite spga×bsa score compared with pasi score to assess clinical response to bms-986165 in patients with moderate to severe plaque psoriasis methods patient population and study design • the phase 2 trial included adult patients with plaque psoriasis for ≥6 months and a body mass index of 18–40 kg/m2 who were eligible for phototherapy or systemic therapy and had moderate to severe disease as defined by affected bsa ≥10%, pasi score ≥12, and spga score ≥312 • patients were randomized to 1 of 5 oral doses of bms-986165 (3 mg every other day, 3 mg qd, 3 mg bid, 6 mg bid, 12 mg qd) or placebo12 • the treatment period was 12 weeks, with an additional 30-day off-treatment follow-up period for safety12 efficacy assessments and outcomes • key efficacy assessments included pasi, spga, bsa, and the dermatology life quality index (dlqi) questionnaire — the primary endpoint was pasi 75 at week 12 • percentage mean change from baseline to week 12 in spga×bsa and pasi score was assessed for the placebo group and all bms-986165 dose groups • spearman correlation coefficients were used to assess the relationship between spga×bsa and pasi or dlqi scores at week 12, as well as between percentage change from baseline in spga×bsa and pasi or dlqi scores at week 12 for all treatment groups. agreement was based on concordance rates • the proportion of patients achieving 75% improvement in spga×bsa (spga×bsa 75) or achieving pasi 75 and the percent improvement from baseline in pasi or spga×bsa were calculated for patients receiving placebo and for the combined group of patients receiving doses of bms-986165 that were most effective (≥3 mg bid) results patient population • this post hoc analysis included all 267 patients who were randomized and treated in the phase 2 trial • patient demographics and baseline disease characteristics were generally similar across treatment groups12 outcomes • the trend in percentage mean change from baseline to week 12 across all bms-986165 treatment groups and the placebo group was similar for spga×bsa (figure 1a) and pasi (figure 1b) figure 1. percentage mean change from baseline by visit in (a) spga×bsa and (b) pasi score in patients with moderate to severe plaque psoriasis treated with bms-986165 or placebo (n=267) a m e an ( se ) ch an ge f ro m b as e li n e , % 0 -20 -40 -60 -80 -100 baseline b m e an ( se ) ch an ge f ro m b as e li n e , % 0 -20 -40 -60 -80 -100 baseline percentage mean change from baseline in spga×bsa percentage mean change from baseline in pasi score week 1 week 2 week 4 week 8 week 12 week 1 week 2 week 4 week 8 week 12 placebo (n=45) bms-986165 3 mg bid (n=45) bms-986165 3 mg qod (n=44) bms-986165 6 mg bid (n=45) bms-986165 3 mg qd (n=44) bms-986165 12 mg qd (n=44) data are percentage mean (se) change from baseline. spga×bsa is the product of spga and bsa scores. bid=twice daily; bsa=body surface area; pasi=psoriasis area and severity index; qd=every day; qod=every other day; se=standard error; spga=static physician’s global assessment. • at week 12 there was a strong correlation between spga×bsa and pasi (figure 2a; spearman correlation coefficient = 0.95) and between percent change from baseline in spga×bsa and pasi (figure 2b; spearman correlation coefficient = 0.95) • at week 12 there was a moderate correlation between spga×bsa and dlqi (figure 3a; spearman correlation coefficient = 0.58) and between percent change from baseline in spga×bsa and dlqi (figure 3b; spearman correlation coefficient = 0.62) • a similar proportion of patients achieved spga×bsa 75 and pasi 75 at week 12 (figure 4a) • the percent improvement from baseline to week 12 for bms-986165 (≥3 mg bid dose groups combined) and placebo was similar for spga×bsa and pasi (figure 4b) 2020 pa & np fall clinical dermatology conference, november 13–15, 2020, orlando, florida copies of this poster obtained through quick response (qr) code are for personal use only and may not be reproduced without written permission from the authors of this poster. references 1. spuls pi et al. j invest dermatol. 2010;130:933-943. 2. walsh ja et al. j am acad dermatol. 2013;69:931-937. 3. duffin kc et al. j drugs dermatol. 2017;16:147-153. 4. gottlieb ab et al. dermatology. 2019;235:348-354. 5. merola jf et al. j invest dermatol. 2018;138:1955-1961. 6. watford wt et al. immunol rev. 2004;202:139-156. 7. tokarski js et al. j biol chem. 2015;290: 11061-11074. 8. volpe e et al. nat immunol. 2008;9:650-657. 9. geremia a et al. j exp med. 2011;208:1127-1133. 10. tucci m et al. clin exp immunol. 2008;154:247-254. 11. gillooly k et al. arthritis rheumatol. 2016;68(suppl10):abstract 11l. 12. papp k et al. n engl j med. 2018;379:1313-1321. 13. gottlieb ab et al. j am acad dermatol. 2017;77:1178-1180. acknowledgments • this work was sponsored by bristol-myers squibb company. professional medical writing and editorial assistance was provided by catriona mckay, phd, and creative assistance during layout was provided by peloton advantage, llc, an open health company, parsippany, nj, and both were funded by bristol-myers squibb company. relationships and activities • abg: grant/research funding (paid to institution): boehringer ingelheim, incyte, janssen-ortho, novartis, ucb, xbiotech; honoraria or consultation fees (paid to abg): abbott (abbvie), amgen, bristol-myers squibb, celgene, eli lilly, incyte, janssen biotech, janssen-ortho, leo pharma, lilly icos, novartis, sun pharma, ucb, xbiotech, avotres (no direct compensation received from avotres); stock options: xbiotech. • bs: honoraria or consultation fees: abbvie, almirall, amgen, arena, boehringer ingelheim, bristol-myers squibb, celgene, dermavant, dermira, eli lilly, gsk, janssen, kyowa hakko kirin, leo pharma, medac, meiji seika pharma, novartis, ortho dermatologics, pfizer, regeneron, sanofi-genzyme, sun pharma, ucb; speaker: abbvie, janssen, lilly, ortho dermatologics; scientific director (consulting fee): corrona psoriasis registry; investigator: abbvie, corrona psoriasis registry, dermavant, dermira. • dt: research support/principal investigator (clinical trials): abbvie, almirall, amgen, biogen idec, boehringer ingelheim, celgene, chugai, dermira, ds-pharma, eli lilly, galderma, gsk, janssen-cilag, leo pharma, msd, novartis, pfizer, regeneron, roche, sandoz-hexal, sanofi, ucb; consultant: abbvie, almirall, celgene, dignity, galapagos, leo pharma, maruho, mitsubishi, novartis, pfizer, xenoport; lectures: abbvie, almirall, amgen, ds-pharma, janssen, leo pharma, msd, novartis, pfizer, la roche-posay, sandoz-hexal, sanofi, target-solution, ucb; scientific advisory board: abbvie, amgen, celgene, ds-pharma, eli lilly, galapagos, janssen-cilag, leo pharma, morphosis, msd, novartis, pfizer, sandoz, sanofi, ucb. • kg: grant support and consulting fees: abbvie, boehringer ingelheim, bristol-myers squibb, celgene, eli lilly, janssen, novartis, ucb; consulting fees: amgen, almirall, dermira, leo pharma, pfizer, and sun pharma. • jfm: consultant and/or investigator for merck, abbvie, dermavant, eli lilly, novartis, janssen, ucb, celgene, sanofi, regeneron, arena, sun pharma, biogen, pfizer, emd sorono, avotres, and leo pharma. • sk, rk, lw, sb: employees and shareholders of bristol-myers squibb company to request a copy of this poster: scan qr code via a barcode reader application scientific content on demand qr codes are valid for 30 days after the congress date. figure 2. correlation between (a) spga×bsa and pasi and (b) percentage change from baseline in spga×bsa and pasi at week 12 for all bms-986165 treatment groups and placebo (n=267) 0 0 5 10 15 20 25 30 35 40 45 50 a spearman correlation coefficient = 0.95 50 100 150 spga×bsa p a si s co re 200 250 300 -100 -100 -80 -60 -40 -20 0 20 40 60 b spearman correlation coefficient = 0.95 -75 -50 -25 change from baseline in spga×bsa, % c h an ge f ro m b as e li n e i n p a si s co re , % 0 5025 10075 spga×bsa and pasi at week 12 percentage change from baseline in spga×bsa and pasi at week 12 spga×bsa is the product of spga and bsa scores. circles represent data points for individual patients. bsa=body surface area; pasi=psoriasis area and severity index; spga=static physician’s global assessment. figure 3. correlation between (a) spga×bsa and dlqi and (b) percentage change from baseline in spga×bsa and dlqi at week 12 for all bms-986165 treatment groups and placebo (n=267) a b spga×bsa and dlqi at week 12 percentage change from baseline in spga×bsa and dlqi at week 12 spearman correlation coefficient = 0.58 spearman correlation coefficient = 0.62 spga×bsa change from baseline in spga×bsa, % 0 50 100 150 200 250 300 -100 -75 -50 -25 0 5025 10075 0 5 10 15 20 25 30 35 d lq i sc o re -100 -50 0 50 100 150 200 250 c h an ge f ro m b as e li n e i n d lq i sc o re , % spga×bsa is the product of spga and bsa scores. circles represent data points for individual patients. bsa=body surface area; dlqi=dermatology life quality index; spga=static physician’s global assessment figure 4. (a) proportion of patients achieving 75% improvement and (b) percent improvement from baseline in spga×bsa or pasi scores at week 12 for the combined group of patients receiving the 3 most effective bms-986165 doses (3 mg bid, 6 mg bid, and 12 mg qd) (n=134) vs placebo (n=45) 70.1 78.4 6.7 13.3 a proportion of patients achieving spga×bsa 75 or pasi 75 0 10 20 30 40 50 60 70 80 90 100 p at ie n ts ac h ie vi n g 7 5 % im p ro ve m e n t, % b percent improvement from baseline in spga×bsa or pasi at week 12 -100 -80 -60 -40 -20 0 20 40 60 80 100 c h an ge f ro m b as e li n e t o w e e k 1 2 , % bms-986165 3 mg bid, 6 mg bid, and 12 mg qd doses combined (n=134) spga×bsa pasi placebo (n=45) bms-986165 3 mg bid, 6 mg bid, and 12 mg qd doses combined (n=134) placebo (n=45) spga×bsa is the product of spga and bsa scores. spga×bsa 75 and pasi 75 are the proportion of patients achieving 75% improvement in spga×bsa and pasi scores, respectively. the box whisker plot shows mean, median, other key percentiles, and outliers. bid=twice daily; bsa=body surface area; pasi=psoriasis area and severity index; qd=every day; spga=static physician’s global assessment. http://www.globalbmsmedinfo.com immediate and long-term efficacy of a two-step topical hyaluronic acid lip treatment elizabeth t. makino, bs ccra mba; priscilla tan, ba; rahul c. mehta, phd research & development skinmedica, an allergan company, irvine, ca, usa presented at the fall clinical dermatology conference series, october 12-15, 2017, las vegas, nv, usa background similar to facial skin aging, visible features of aged lips can be attributed to degradation of structural components of the skin including collagen and elastin fibers. key features of lip aging include loss of volume, color, and definition as well as increases in lines/wrinkles and uneven skin texture. as a result these factors result in the loss of contrast between lips and surrounding skin and is associated with an older, aged appearance. objective to assess the efficacy and tolerability of a novel, topical two-step lip treatment that contains hyaluronic acid (ha⁵ ls). results ● thirty-one female subjects, aged 22-40 years with fst ii-v who identified as caucasian, african american, native hawaiian or other pacific islander and asian ethnicities, completed the study. o subjects presented with mean scores of 3.11 for lip scaling (dryness) and 4.14 for overall lip condition. o five subjects voluntarily withdrew from the study (not due to adverse events). ● immediate effects: within 15 minutes of application, statistically significant improvements in mean scores compared to baseline were observed for all parameters (all p<0.001; wilcoxon signed-rank test; n=36). ● long-term effects: continuing significant improvements at weeks 2 and 4 compared to baseline for all parameters, except for cupping at week 2 (all p≤0.026; wilcoxon signed-rank test; week 2: n=32, week 4: n=31). ● ha⁵ ls was well-tolerated with no increase in mean tolerability scores at each evaluation time. by week 4, erythema, burning, stinging, itching, and tightness improved 100% in mean change from baseline. o no treatment-related adverse events were reported during the study. ● the lip wrinkle image analysis supported the long-term improvements observed by the investigator, with significant improvements at week 4 post-application in all parameters (all p≤0.001; paired t-test; n=31). ● statistically significant improvements in mean scores for corneometer and digital caliper measurements at weeks 2 and 4 indicate an increase in intrinsic hydration and lip thickness, respectively, with continued use. ● ha5 ls was highly rated by subjects with a statistically significant proportion of favorable responses for instant and long-term self-perceived efficacy and product texture and attributes. o at week 4, a significant proportion of subjects felt that ha5 ls made their lips look and feel more full (90%), made their lips look naturally plump (90%) and added more volume to their lips (87%). conclusions results from this study suggest that ha⁵ ls addresses the key features of lip aging, providing both instant and long-term benefits. ha⁵ ls may provide an alternative option to patients seeking a non-invasive treatment to rejuvenate and enhance the appearance of their lips with intrinsic benefits beyond cosmetic lipsticks. study design • open-label, single-center clinical usage study. • four week study duration with visits at baseline, week 2 and week 4. subject inclusion criteria • female subjects aged 22-40 years with fitzpatrick skin types (fst) i to v who have self-perceived and clinically determined average-size lips. • must be a non-smoker and have not smoked within the last 5 years. • must have mild to moderate dryness on the lips at baseline with a score between 3 and 6 on modified griffiths’ scale. • must have mild to severe lip condition (lip texture/visual roughness and lines/wrinkles) with a score of 3 or higher on the modified griffiths’ scale. treatment subjects were instructed to apply ha⁵ ls (step 1: lip treatment, step 2: lip plumper) at a minimum of three times a day to ensure coverage 8 hours a day for four weeks. subjects were instructed to apply ha⁵ ls at least once prior to each follow-up visit, but not within one hour of the visit. clinical assessments to capture the immediate effects of applying ha⁵ ls, clinical grading and efficacy parameters were performed post-application at baseline with product on the lips. long-term efficacy was assessed at week 2 and week 4. the following efficacy parameters were assessed on the lips using a 0-9 scale, where 0=none (best possible condition), 1-3=mild, 4-6=moderate, and 7-9=severe (worst possible condition), with half points allowed as necessary to differentiate degrees of severity: the efficacy parameters of cupping and scaling were assessed on a 0-6 scale, as described below: • cupping: 0=full, plump, 1=drawing at lip margin, 2=isolated area cupping at margin, 3=few areas cupping along lip margin, 4=cupping all along lip margin, 5=cupping more than lip margin, and 6=entire surface cupping • scaling: 0=none, 1=dull surface, 2=powdery flakes, 3=few lifting edges, 4=generalized lifting scale-mild, 5=generalized lifting scale-moderate, and 6=generalized lifting scale-severe tolerability assessments for erythema, edema, burning, stinging, itching and tightness were conducted on a 4-point scale (0=none, 1=mild, 2=moderate, 3=severe) at all visits. subject self-assessment questionnaires subjects completed a self-assessment questionnaire at all visits. instrumentation standardized digital photographs were taken using the visia-cr imaging system (canfield imaging systems) at baseline (preand post-application), week 2 and week 4 (preand post-application). a lip wrinkle image analysis was conducted with a software developed by stephens & associates using image pro plus v7 software (media cybernetics, inc., rockville, maryland). a digital caliper was used to measure lower lip plumpness, and corneometer cm 825 (courage + khazaka, germany) was used to measure skin hydration. disclosures this study was sponsored by allergan. all authors met the icmje authorship criteria. all authors are employees of allergan. figure 4: long-term effects (no product on the lips) figure 5: lip wrinkle image analysis on visia-cr standard 2 photographs figure 2: instant effects: baseline vs. baseline post-application (within 15 minutes of application) female subject, age 33, fitz iii 0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5 scaling (dryness, flaking) cupping lip lines/wrinkles overall lip condition lip color/rosiness overall lip definition / lip contour lip texture / visual roughness lip plumpness m ea n sc or es baseline post-application female subject, age 33, fitz iii female subject, age 31, fitz ii baseline week 4 • lip lines/wrinkles • overall lip condition • lip color/rosiness • overall lip definition/lip contour • lip texture/visual roughness • lip plumpness figure 3: long-term effects: investigator assessments (no product on the lips) 0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5 scaling (dryness, flaking) cupping lip lines/wrinkles overall lip condition lip color/rosiness overall lip definition/ lip contour lip texture/ visual roughness lip plumpness m ea n sc or es baseline week 2 week 4 figure 1: instant effects: investigator assessments (with product on the lips) total count total length (mm) total width (mm) total area (mm2) total depth (arbitrary units) baseline 39.89 63.59 26.50 36.63 298.53 baseline post-application 27.80* 41.24* 17.25* 22.02* 174.34* week 4 post-application 22.81* 33.86* 13.92* 17.94* 145.48* *statistically significant improvements vs. baseline (all p≤0.001; wilcoxon signed-rank test for total count, paired t-test for all other parameters; baseline post-application: n=35, week 4 post-application: n=31) figure 6: corneometer and digital lip caliper measurements corneometer measurements for hydration (mean scores) digital lip caliper measurements for thickness in mm (mean scores) baseline 23.68 34.33 week 2 32.67* 34.94^ week 4 36.26* 36.17^ *statistically significant improvements vs. baseline (all p<0.001; paired t-test; week 2: n=32, week 4: n=31) ^statistically significant improvements vs. baseline (all p≤0.032; paired t-test; week 2: n=32, week 4: n=31) fc17posterallerganhaliptx.pdf combining in-office chemical peel procedures with topical therapy of a comprehensive pigmentation control product for multi-ethnic subjects with moderate to severe facial hyperpigmentation katie h. schneider, bs, cra; lisa t. goberdhan, ba; elizabeth t. makino, bs, ccra, mba; rahul c. mehta, phd research & development skinmedica, an allergan company, irvine, ca, usa presented at the fall clinical dermatology conference series, october 12-15, 2017, las vegas, nv, usa background skin discoloration is a common concern with limited treatment options for multi-ethnic patients due to the increased risk of post inflammatory hyperpigmentation (pih). the use of superficial chemical peels is an effective and well tolerated treatment for patients of various ethnic origins. combination therapy such as brightening topicals paired with chemical peels has been shown to be more effective in addressing hyperpigmentation. objective to assess the efficacy and tolerability of a daily topical regimen (hq free) in combination with a series of three superficial chemical peels in patients with moderate to severe facial hyperpigmentation. results ● fourteen male and female subjects (fst iii, iv and vi) presenting with moderate to severe hyperpigmentation completed the twelve week study. three subjects discontinued the study, due to treatment-related adverse events which were skin-related. ● at week 8, significant improvements in all efficacy parameters including overall hyperpigmentation, overall photodamage, and skin tone unevenness (p<0.03; n=16; student’s paired t-test) ● at week 12, all efficacy parameters continued to show significant improvements (p<0.01; n=14; student’s paired t-test) ● the combination treatment of vp and lyt2 was highly-rated at week 12 by subjects in self-perceived efficacy and patient satisfaction (figure 5) ● at study completion, 100% of subjects felt moderately and very satisfied with the combination regimen. conclusions these results demonstrate the aesthetic benefits to multi-ethnic patients with use of a daily non-hq regimen combined with a series of 3 superficial chemical peels. study design • open-label, single-center clinical usage study • twelve week study duration with visits at baseline, week 4, week 8 and week 12 subject demographics • male and female subjects (n=17) aged 36-69 years, with fitzpatrick skin types (fst) iii, iv and vi, who identified as asian, hispanic, african american, or caucasian ethnicities presenting with moderate to severe hyperpigmentation (as determined by a grade of 4-9 on the overall hyperpigmentation scale) were enrolled in the study. test products • comprehensive hq-free pigmentation control product (lyt2) • superficial chemical peel (vp) treatment subjects received a series of three vp treatments every four weeks during the twelve week study. a basic skincare regimen of cleanser, moisturizer, and physical sunscreen was provided to subjects in addition to lyt2 which was applied post-peel approximately 5-7 days or once facial peeling was complete. after cleansing, subjects were instructed to apply a thin layer of lyt2 to the entire face morning and evening. clinical assessments at all visits, the investigator graded the subjects’ skin on the following facial parameters (0-9 scale): • overall hyperpigmentation • overall photodamage • skin tone unevenness • global improvement in hyperpigmentation (0-4 scale; at follow-up visits only) subject self-assessment questionnaires subjects also completed a self-assessment questionnaire at all follow-up visits (weeks 4, 8 and 12) regarding the appearance of the facial skin. instrumentation standardized digital photographs of the face were taken at all visits using the visia-cr imaging system (canfield scientific, inc.) reflectance confocal microscopy (rcm) images (vivascope® 1500, caliber imaging and diagnostics) were captured at baseline and week 12 visits on three subjects. disclosures this study was sponsored by allergan. all authors met the icmje authorship criteria. all authors are employees of allergan. female subject, age 36, fitz iii left to right: baseline & week 12 after 3 vp treatments, and 9 weeks of twice daily use of lyt2 improvements observed in overall hyperpigmentation and overall photodamage at week 4 through week 12 with statistically significant improvements observed at weeks 8 and 12 (p<0.03; student’s paired t-test). figure 5: subject self-assessment questionnaire at week 12 figure 6: investigator efficacy assessments of the face female subject, age 45, fitz iii left to right: baseline, & week 12 after 3 vp treatments, and 12 weeks of twice daily use of lyt2 figure 4: visible improvements at week 12 female subject, age 44, fitz iii left to right: baseline & week 8 after 2 vp treatments, and 6 weeks of twice daily use of lyt2 figure 3a: dermoscopy image baseline vs. week 12 female subject, age 56, fitz iv 3a) dermoscopy of pigmented lesion showing improvements in skin tone at baseline (left) versus week 12 (right) 3b) rcm single frame (0.5 x 0.5mm) at baseline,(left) versus week 12 (right) showing a decrease in pigmented keratinocytes (bright white round cells) figure 3b: rcm image baseline vs. week 12 figure 1: visible improvements at week 8 figure 2: visible improvements at week 12 fc17posterallerganpeels.pdf microsoft word september 2020 rescomp 905 proof.docx skin september 2020 volume 4 issue 5 copyright 2020 the national society for cutaneous medicine 404 resident competition research articles dermatologists’ perceptions and use of electronic health record systems olivia katamanin1, alex m. glazer, md2 1university of michigan, ann arbor, mi 2division of dermatology, university of arizona college of medicine, tucson, az electronic health records (ehr) have been lauded as the standard of practice for 21st century medicine.1 ehr uses a systematically organized digital portfolio with the goals of increasing efficiency and improving charting and quality of patient care.2 despite its widespread adoption, ehr has been accompanied by a multitude of potential negative implications on clinical practice, physician burnout, patient communication, and financial success.3 there have been no studies specifically assessing dermatologists’ perceptions of ehr. the purpose of this study is to determine us dermatologists’ perceptions and use of ehr within their clinical practice. abstract introduction: electronic health records (ehr) have been adopted and integrated into medical practices over the past 20 years. many positive and negative implications have been described by physicians using ehr. this study aims to us dermatologists' perceptions and use of ehr within their clinical practice. methods: a validated survey was administered to us dermatologists at a national educational conference to assess use and perceptions of ehr. results seventy-two percent (291/400) of those sampled completed greater than 90% survey and were included in outcome analysis. eighty-six percent of the participants were currently using or had used ehr. most dermatologists felt that ehr negatively impacted their workflow efficiency and face-to-face time with patients. a portion of dermatologists thought that ehr improved their documentation. limitations: selection bias may have led those with strong beliefs with ehr more likely to complete the entire survey. conclusion: despite widespread adoption, most dermatologists have a negative impression of ehr and felt that it interfered with their ability to effectively see patients. interventions to improve ehr should focus on improving workflow efficiency and maximizing the amount of time dermatologists can spend with patients. introduction skin september 2020 volume 4 issue 5 copyright 2020 the national society for cutaneous medicine 405 the survey instrument was validated and administered to us dermatologists attending a national educational conference. participants provided verbal consent to participate in the study, and the results of the survey were not disclosed until the end of the data collection to minimize response bias. respondent demographics were compared to american academy of dermatology membership data to verify representative nature of the responding subset. of the 400 participants surveyed, 291 (72.7%) answered greater than 90% of questions and were included in the outcome analysis. eighty-six percent (250/291) of the participants were currently using or had plans to implement ehr within the next 2 years. eleven percent (32/291) reported no desire to use or implement ehr within the next two years (figure 1). while most dermatologists felt that ehr negatively impacted their workflow efficiency (74.9%) and face-to-face time with patients (57.6%), the majority (56.9%) felt it improved their documentation (figure 2). the most common reasons dermatologists cited for not adopting ehr were interference with doctor-patient relationship (25.6%), incentives/penalties not worth it (17.4%), too complicated (14%) and cannot afford the cost (9.3%) (figure 3). most dermatologists surveyed are currently utilizing or have plans to implement ehr in their practice in the near future. overall, dermatologists have a negative view of ehr on their clinical practice. despite its widespread adoption, most dermatologists felt that ehr decreased their face-to-face time with patients and negatively impacted their clinical efficiency. less than half of dermatologists felt that ehr improved their overall patient services. the only positive aspect of ehr dermatologists cited was for improved documentation. a greater proportion of dermatologists felt that ehr negatively impacted their patient interaction than thought ehr improved their documentation. figure 1. dermatologists’ use of ehr limitations include selection bias since those who hold strong beliefs about ehr may have been more likely to complete the entire survey. additionally, social desirability bias may have led dermatologists to respond more negatively to conform with the overall negative sentiment of ehr among other physicians. the overall negative sentiment toward ehr has been echoed in other ambulatory specialties.4 system malfunctions, lack of an accessible interface, and increased screen methods results discussion conclusion skin september 2020 volume 4 issue 5 copyright 2020 the national society for cutaneous medicine 406 figure 2. impact of electronic health record systems on provider figure 3. dermatologists’ reasons for not using electronic health record skin september 2020 volume 4 issue 5 copyright 2020 the national society for cutaneous medicine 407 time requirements are some possible culprits of the physicians’ dissatisfaction with ehr.5 the improved documentation associated with ehr may be coming at the cost of the doctor-patient relationship. further studies are needed to weigh the benefits of ehr, investigate the amount of time dermatologists spend using ehr, and to classify specific ways ehr can become more user friendly. until a better system that consistently improves the physician-patient relationship and patient outcomes is widely available, dermatologists should optimize their workflow to maximize their time with patients and minimize the amount of time they spend interfacing with their ehr. conflict of interest disclosures: none funding: none corresponding author: alex m. glazer, md university of arizona 7165 n pima canyon drive tucson, az 85718 email: alexglazermd@gmail.com references: 1. refs ventres w, kooienga s, vuckovic n, et al. physicians, patients, and the electronic health record: an ethnographic analysis. ann fam med 2006; 4(2):124-131. 2. lakbala p, dindarloo k. physicians’ perception and attitude toward electronic medical record. springerplus. 2014; 3: 63. doi: 10.1186/21931801-3-63 3. read-brown s, hribar mr, reznick lg, et al. time requirements of electronic health record use in an academic ophthalmology center. jama ophthalmol. 2017;135 (11): 1250-1257. 4. read-brown s, hribar mr, reznick lg, et al. time requirements of electronic health record use in an academic ophthalmology center. jama ophthalmol. 2017;135 (11): 1250-1257. 5. jetté n, kwon c. electronic health records—a system only as beneficial as its data. jama netw open. published online september 18, 20192(9):e1911679. doi:10.1001/jamanetworkopen.2019.11679 microsoft word july 2020 org 838 proof returned.docx skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 321 original research association between housing instability and severity of psoriasis and psoriatic arthritis: a cross-sectional study jalal maghfour, ms1, frances gill, bs, mph1, justin olson, bs1, andrea murina, md1 1tulane university school of medicine, new orleans, la psychological stress has been shown to trigger and exacerbate a number of dermatological conditions, including psoriasis, which is thought to be due to an upregulation of inflammatory cytokines.1-3 many key stress mediators are produced locally within the skin, and environmental stressors can impair the barrier function of the skin. a cross-sectional study showed that health related quality of life in psoriasis patients was significantly associated with their demographic and socioeconomic characteristics, including employment status.2 stress has been shown to be a precipitating factor in patients with psoriasis. literature review demonstrated that 31-88% introduction: psoriasis and psoriatic arthritis are interrelated chronic inflammatory disorders that can be exacerbated by stress. the impact of housing instability on severity of psoriasis and psoriatic arthritis (psa) has not been examined. methods: an eight-question survey was administered to 59 psoriasis participants, with and without psa, to assess participants' housing status. the severity of psoriasis and psa diseases was assessed using body surface area (bsa) and clinical disease activity index of psoriatic arthritis (cdapsa) measurements respectively. a multivariate linear regression model was used to predict bsa and cdapsa scores differences among participants. results: housing unstable psoriasis participants had a higher average bsa than housing stable psoriasis participants (14% vs 7.1%). using a regression equation model, housing status and smoking were significant predictors (p<0.04). housing unstable psa participants [13 (33%)] were also found to have a higher average cdapsa than housing-stable psa participants [26 (66%)] (31 vs 16.7). housing instability was the only variable to predict differences in cdapsa scores among psa participants (p=0.021). housing unstable participants had a higher bsa even on biologics (21.3% vs 1.65%; p < 0.001), oral therapy (14.6% vs 4 %; p<0.001) and phototherapy (10% vs 4%; p=0.031). discussion: this study demonstrated that housing instability might be associated with an increased severity of psoriasis and psa and may also affect treatment selection. conclusion: housing instability is a psychosocial stressor that could be an important element to consider in the management of psoriasis patients. abstract introduction skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 322 of patients report stress as not only being a precipitating trigger for their disease, but a continuous cause of exacerbation of their psoriasis.4 housing instability, lacks of housing affordability, and homelessness have been shown to be one of the many factors that contribute to chronic stress among lowincome individuals.5 housing instability does not have a standard definition, but encompasses a number of challenges from trouble paying rent, to overcrowding and frequent moves. housing instability was found to be a source of chronic stress and several studies linked housing instability to adverse health outcomes.6 in 2013, over one in four renters paid more than half their income in rent. this number has risen by more than 3 million households since 2000 and is projected to continue to increase over the next five to ten years. non-white households are projected to endure the bulk of this change, as are renters over the age of 65.5 rates of rent burden are particularly demanding in highcost metro areas such as new orleans, louisiana , where our study was conducted. due to high cost living, doubling up has been increasing. this is a phenomenon that results from economic hardships which forces individuals to live with others. it has been demonstrated that doubling up is not only a risk factor for homelessness but it can also be detrimental to the health of affected individuals.6 from 2005 to 2008, the number of people doubling up increased five percent, with an increase to 11.6% from 2006 to 2009.6 the severity in rent burden, due to increased rent and decreased income, was shown to be a source of psychosocial stress and financial instability particularly for lowincome families with children.7 moreover, the link between chronic stress and negative health outcomes is well established. it was found that many individuals suffering from chronic stress are at increased risk for hypertension and diabetes even after adjusting for potential confounders.8 similar studies have established that stress secondary to housing instability contributes to adverse health outcomes in the general population.9 yet, little to no studies have been conducted on the impact of housing instability, as a psychosocial stressor, on chronic inflammatory dermatologic conditions such as psoriasis and psoriatic arthritis. in this study, we investigated whether or not housing instability is associated with increased severity of psoriasis and psoriatic arthritis. participants were asked a series of questions pertaining to homelessness, rent payment, and moving frequency. questions were derived from a validated study based on the definition of housing instability.10 the primary hypothesis is that psoriasis and psoriatic arthritis participants with at least one element of housing instability have more severe psoriatic and psa disease as clinically assessed by a higher bsa and cdapsa scores. population studied we assessed housing instability among established psoriasis and psoriatic arthritis patients at a safety-net hospital in new orleans, louisiana. this study was approved by tulane university institutional review board (irb). we administered an eight-question housing instability survey to all consenting participants > 18 years of age, who were seen in dermatology clinic. methods skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 323 the survey was administered from november 2018 through june of 2019. the severity of psoriasis and psa was clinically assessed through measurement of bsa and cdapsa scores respectively, at the time of the office visit. these assessments were performed by a board-certified dermatologist. measures patients were stratified based on sex, race as well as alcohol and cigarette use. patients’ current treatment regimen and all other medications were recorded at the time of the visit. housing unstable participants, who had at least two or more elements of housing instability or currently homeless, were offered a pre-prepared packet of housing and rent assistance resources available in the community. statistical analysis a multivariate linear regression analysis was performed to assess the effects of several variables, in addition to housing instability, on bsa and cdapsa scores. the additional variables included smoking, alcohol, sex and race. for multiple linear regression models, housing instability was coded as 0 and stable housing was coded as 1. similarly, sex was coded as 1 for male and 2 for female. smoking, alcohol, race were coded as yes or no. the statistical hypothesis was that housing instability is associated with increased severity of psoriasis and psa, resulting in higher bsa and cdapsa scores respectively. an unpaired t-test was performed to compare the average bsa between housing stable and housing unstable psoriasis participants who were on similar treatment regimen. both analyses were conducted using ibm spss statistics 20. we assessed the housing status of 59 psoriasis patients, of which 35 had concomitant psa. among the twenty-four patients (41%) with housing instability, three (12.5%) were currently homeless; nine (15%) patients had lived in more than one place in the last year. seven (11%) patients had moved in the last year or moved in with someone to lower household expenses. twelve (20%) patients reported falling behind on their rent or mortgage at some point in the last year. among housing unstable psoriasis participants with or without psa disease, there were 20 (83%) males, 11 (46%) were caucasians, seven (29.2%) were african american, two (8.3%) were hispanics. of 24 housing unstable psoriasis participants, 12 (50%) reported tobacco use, eight (33%) reported alcohol consumption and two participants (8.3%) reported smoking and alcohol use. the remaining two participants (8.3%) did not report any alcohol or cigarettes use. among housing stable psoriasis participants, 11 (31.4%) reported tobacco use, 13 (37%) reported alcohol use and three (8.6%) reported using both substances. eight participants (22.5%) did not report any alcohol or cigarettes use. housing unstable psoriasis participants [24 (41%)] had a higher average bsa than housing stable participants [35 (60%)] (14% vs 7.1%). using a significant multiple linear regression analysis, a significant regression equation results skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 324 was found (f(7,51)=2.567, p=0.024); r2 = 0.2605. participants’ predicted bsa was equal to 9.383 + 3.55 (housing instability) + 8.44 (smoking) + 1.40 (alcohol) + 5.5 (male sex) 11.73 (race(b)) 6.4 (race(h)) 9.830 (race(w)). as seen in table 2, both smoking and housing instability were significant predictors in accounting for bsa differences among psoriasis participants (p <0.04). similarly, psa participants who reported any element of housing instability [13(33%)] had a higher cdapsa scores than housing stable psa participants [26(66%)] (28.4 vs 16.8). a multiple linear regression model was performed to predict participants’ cdapsa scores based on housing status, smoking, alcohol, race and sex. the regression equation was not significant f(7,31)=1.903,p=0.103); r2=0.30. in the cdapsa model, housing instability was the only significant variable in accounting for the differences in cdapsa scores among psa participants (p =0.021) (table 3). remaining variables including smoking, alcohol and sex were not significantly associated with increased cdapsa scores among housing unstable participants. in terms of treatment, a total of 15 (25%) psoriasis participants were on long-term biologic (> 1 year) at the time of questionnaire. six (25%) housing unstable psoriasis participants had a higher average bsa than housing stable participants [10 (28%)] (21.3% vs 1.65%; p <0.001). housing unstable psoriasis participants [3(12.5%)] on oral systemic therapy (such as apremilast or methotrexate) had a higher average bsa than housing stable psoriasis participants [7(20%)] (14.6%vs 5.6%; p <0.001). housing unstable psoriasis participants [3(12.5%)] were undergoing phototherapy had a higher average bsa than housing stable participants [7(11.8%)] (10% vs 4%; p=0.031). several psoriasis patients were not undergoing any treatment related to their disease. nine psoriasis patients with at least one element of housing instability had an average bsa of 7.5%. among those nine patients, three patients were currently homeless with an average bsa of 12%. table 1. prevalence of housing instability markers amongst psoriasis participants in a dermatology clinic table 2. coefficients used in predicting outcome of bsa among psoriasis participants. co efficients estimate std. error t value pr (>|t|) intercept 9.383 5.907 1.589 0.1183 housing unstable y 3.546 3.221 1.101 0.0376* smoking y 8.437 3.593 2.348 0.0228* alcohol 1.394 3.83 0.412 0.682 sex m 5.515 3.115 1.771 0.0826 race b -11.726 6.383 -1.837 0.072 race h -6.379 6.571 -0.0971 0.3362 race w -9.83 5.82 -1.689 0.0973 *p<.05 respondent type patients, no.(%) gender = male (%) 20 (34) currently homeless (%) 3 (5) lived in more than one place during the last year (%) 9 (15) moved in the last year due to cost (%) 2 (3) doubled up to save on household expenses 5 (8) skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 325 table 3. coefficients used in predicting outcome of cdapsa scores among psoriatic arthritis participants. co efficients estimate std. error t value pr (>|t|) (intercept) 16.16 12.93 1.25 0.220 housing unstable 20.647 8.462 2.44 0.021* smoking -8.426 8.595 -0.98 0.33 alcohol 13.374 8.327 1.606 0.12 sex m -7.351 8.284 -0.899 0.38 race b 8.088 14.79 0.547 0.59 race h -1.202 14.64 -0.082 0.94 race w -4.61 13.96 -0.33 0.74 *p<.05 psoriasis is a chronic skin disease with a complex multifactorial etiology. it is due to dysregulation of immune cells triggered by environmental and genetic factors including stress, smoking and alcohol consumption.8 it has been reported that cellular stress leads to formation of free radicals that promote inflammatory process, and exacerbate disease.9 psa is an inflammatory musculoskeletal disease that occurs in 2030% of patients.11 mechanical stress and trauma are known to precipitate psoriatic arthritis. the results of this study showed that housing instability is significantly associated with increased bsa among psoriasis participants. in addition, smoking was a significant covariate in predicting differences in average bsa score among psoriasis participants. previous reports have demonstrated the role of smoking on the increased severity of both psoriasis and psoriatic arthritis. even though smoking was not a significant predictor for cdapsa scores among psa participants, studies have shown that psoriasis patients who smoked had an earlier onset of arthritis in comparison to non-smoker groups.12 while cdapsa scores were higher among housing unstable psa participants, the difference was not significant in the linear multivariable regression model. however, housing instability was a significant variable in accounting for differences in cdapsa scores among psa participants (p=0.021). the role of psychosocial factors such as socioeconomic factors including employment status on severity of psoriasis has been a focus of attention in the recent years. although housing instability has been studied among public health researchers where it was linked to increased adverse health outcomes, studies on the impact of housing instability on inflammatory dermatologic conditions have been limited. in this study, we also found that housing instability may impact treatment availability and selection. participants who reported unstable housing while being on biologics, oral systemic therapies and phototherapy had a higher bsa than similarly treated patients without housing instability. although the mechanism is unclear, this may be due to the direct impact of housing instability, as a stressor, on achieving therapeutic benefits. previous studies have demonstrated that psoriasis patients who have experienced psychological stress had a delayed clearance of their psoriasis on puva therapy.13 we did not control for adherence, as it was difficult to do in this setting. adherence can be an important element in assessing treatment efficacy and may account for the differences seen among patients undergoing various treatments. for instance, phototherapy is an effective way to treat psoriasis but requires reliable discussion skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 326 transportation in order to attend 2-3 phototherapy visits per week. a home address delivery is required for psoriasis and psa patients that require refrigeration, such as the biologic drugs. most patients with housing instability had an average bsa considered to be in the severe range (>10% bsa) and are more likely to require advance therapies. our clinic offers an outpatient pharmacy that allows single dose pickup, so that housing unstable patients can self-inject as needed or plan regular nursing visits to inject their biologic drugs. limitations of the study include cross sectional study by design, small number of surveyed patients. the study sampled patients from a safety-net dermatology clinic, and most patients had some form of health coverage. the health insurance status of patients seen at university medical center is 60% medicaid/medicare and 20% uninsured. the same assessment performed at a free clinic may yield different results. in summary, assessing for housing instability is important for dermatologists to consider because it may be associated with more severe psoriatic disease and can also limit treatment selection. dermatologists can consider linking their patients to social support services in order to reduce stressors due to housing instability, which may also improve overall clinical outcomes. conflict of interest disclosures: dr. murina is a speaker for abbvie, celgene, janssen and novartis. funding: none corresponding author: jalal maghfour, ms 1430 tulane avenue, #8031 new orleans, la 70112 email: jmaghfou@tulane.edu references: 1. alexopoulos, a., & chrousos, g. p. (2016). stress-related skin disorders. rev endocr metab disord, 17(3), 295-304. doi:10.1007/s11154-0169367-y 2. chen, y., & lyga, j. (2014). brain-skin connection: stress, inflammation and skin aging. inflamm allergy drug targets, 13(3), 177-190. doi:10.2174/1871528113666140522104422 3. tampa, m., sarbu, m. i., mitran, m. i., mitran, c. i., matei, c., & georgescu, s. r. (2018). the pathophysiological mechanisms and the quest for biomarkers in psoriasis, a stress-related skin disease. dis markers, 2018, 5823684. doi:10.1155/2018/5823684 4. rousset, l., & halioua, b. (2018). stress and psoriasis. int j dermatol, 57(10), 1165-1172. doi:10.1111/ijd.14032 5. charette, a. c. h. (2015, september 21). projecting trends in severely cost-burdened renters: 2015–2025 | joint center for housing studies of harvard university. retrieved march 3, 2020, from https://www.jchs.harvard.edu/researchareas/reports/projecting-trends-severely-costburdened-renters-2015%e2%80%932025 6. frederick, t. j., chwalek, m., hughes, j., karabanow, j., & kidd, s. (2014). how stable is stable? defining and measuring housing stability. journal of community psychology, 42(8), 964-979. doi:10.1002/jcop.21665 7. bartfeld, judi and rachel dunifon (2005). "statelevel predictors of food insecurity among households with children" journal of policy analysis and management 25(4): 921-942 and newman, sandra j. and c. scott holupka (2015). "housing affordability and child wellbeing" housing policy debate 25(1):116-151 8. kushel, m. b., gupta, r., gee, l., & haas, j. s. (2006). housing instability and food insecurity as barriers to health care among low-income americans. j gen intern med, 21(1), 71-77. doi:10.1111/j.1525-1497.2005.00278.x 9. hernández, d., phillips, d., & siegel, e. l. (2016). exploring the housing and household energy pathways to stress: a mixed methods study. int j environ res public health, 13(9). doi:10.3390/ijerph13090916 conclusion skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 327 10. burgard, s. a., seefeldt, k. s., & zelner, s. (2012). housing instability and health: findings from the michigan recession and recovery study. soc sci med, 75(12), 2215-2224. doi:10.1016/j.socscimed.2012.08.020 11. vijayaraghavan, m., kushel, m. b., vittinghoff, e., kertesz, s., jacobs, d., lewis, c. e., bibbinsdomingo, k. (2013). housing instability and incident hypertension in the cardia cohort. j urban health, 90(3), 427-441. doi:10.1007/s11524-012-9729-z 12. naldi, l. (2016). psoriasis and smoking: links and risks. psoriasis (auckl), 6, 65-71. doi:10.2147/ptt.s85189 13. vardy, d., besser, a., amir, m., gesthalter, b., biton, a., & buskila, d. (2002). experiences of stigmatization play a role in mediating the impact of disease severity on quality of life in psoriasis patients. br j dermatol, 147(4), 736-742. doi:10.1046/j.1365-2133.2002.04899. microsoft word july 2020 edt bhatia 929 proof final.docx skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 309 editorials dermatology and virtual realities with industry: “it’s not your father’s pharma anymore” neal bhatia, md1 1director of clinical dermatology, therapeutics clinical research, san diego, ca did you ever think you would see the day when pharma reps would go from driving all over town, sitting endlessly in waiting rooms, and bringing in sweets for a few minutes of detail to now working from home, making virtual calls over lunch, staying in their cars while we rush out to get samples, and watching the entire system on its knees? everyone in pharma, from drug reps to medical science liaisons to executives have been under stay-at-home policies, including digital sales tools and virtual meetings for face-to-face visits. advisory board meetings, speaker training meetings for promotional education, and investigator meetings for clinical trials have all been conducted virtually. the new reality is here and is not retreating anytime soon, but the question becomes does the adaptation during the pandemic just accelerate what was probably coming anyway? as i write this on father’s day, i can imagine how many of you whose parents were dermatologists remember the “good ol’ days” when anything was the rule. so, in the old normal, just like the new normal, or whatever level of normal there is left, we still have the template of how to interact professionally with our colleagues from industry. on the one hand, the sales reps working virtually should pay close attention to the clinic’s time allotted for patients and work. they should still keep professionalism with approach and appearance, maintain the message about business rather than making it personal, and make attempts to deliver the goods. if appointments weren’t a good idea before, maybe they are now? i have been coaching a lot of my reps that a few days of virtual encounters and one or two days making masked calls in the parking lot would be more efficient for them, saving days of sitting in traffic and reducing exposures. at the same time, dermatologists have to keep a similar level of professionalism on virtual interactions and understand the nature of this new chance to do their job. sales personnel are not caterers or avenues for aspirations of medical education, but the virtual lunch with the clinic staff can be an efficient new wave of marketing and promotion. and, if anyone is worried about the sunshine act reporting over $10, a lot of good lunches cost about $9. until we feel like we have fully opened back up, patients and clinic staff may be somewhat relieved about not having sales reps coming in the office for now. patients will wonder if the reps have just come from calling on another clinic, who they have been exposed to, and if they utilize enough ppe to keep them safe, aside from the usual concern of taking time away from the physicians. by the same token, the reps might have that same concern about being around patients who could have been exposed to not just the coronavirus but anything that could be spread for the next pandemic. in a way, it makes the interactions with the physicians a bit less risky when the skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 310 message can be more directed. there won’t be the risk of patients overhearing catchphrases such as “thanks for the last few prescriptions,” “help me out, i am in a contest,” and “can i count on your support?” business experts will still agree that an effective encounter between colleagues or with customers requires being in the same room…simple body language, handshakes, tones of voice, and facial expressions are integral to communication and to solidify relationships with a customer. by not being able to meet in-person, will that lead to a dilution of influence of sales reps? and, with industry overall? as small dermatologycentric pharma companies slowly become extinct or become consolidated puzzle pieces of big pharma, the most painful part for dermatologists, aside from the cost and access issues that we face with each written prescription/suggestion, is the difficulty in establishing working relationships. the turnover of names and faces, as well as the loss of contact with longstanding members of the dermatology fraternity, makes the opportunity to collaborate more challenging. at many levels, from local dermatology societies on up, working with big pharma to gain interest and support for medical education was already difficult with all of the firewalls and issues that are fundamental to big pharma. moreover, without in-person connections the struggle to keep dermatology relevant will continue. there is no questioning big pharma’s dedication to access programs, direct-to-consumer messaging, and sponsorship of patient advocacy initiatives, which have all given promising hope to patients for treatment awareness and options they might not have had in the past…especially in the biologics market. by contrast, in a virtual world, sample programs and patient support initiatives for dermatology might be harder to gain traction in clinics. there were times when the executives and leaders of the companies would not only be visible at meetings but very interactive and known by face and name. by contrast, big pharma can vary its appearance ranging between having little connection to dermatology, to companies that have hired dermatology veterans to sales, professional relations, and medical affairs, seeming to try to understand how the dermatology family operates. it is easy to be entertained by the scripts and “buzzword bingo” that big pharma and corporations foster and train, and i can always tell when anyone has seen the light about how dermatology and doesn’t follow the script. however, the problem with less time in person and more virtual reality is that there will be fewer opportunities for checks and balances as well as conversations with those in corporate positions who can make decisions. with that comes the risks of dermatologists becoming marginalized as advisors when it comes to planning the future, ultimately running the risk of not being called to participate if they rock the boat. the other risk of virtual reality is the development of promotional speakers for industry, who for now have no restaurants to speak in and no clinicians or staff to speak to…except on a virtual meeting. but with the new virtual world, does the trend of negative perceptions continue not only with dermatologists who make it clear that they will stop writing the drugs in question if they are not invited to advisory boards, speaker training meetings, or sponsored travel to speak? those days might be fewer when the opportunities for promotional speaking could become more streamlined or give way to more cme programs if fatigue for virtual meetings continues to increase. even more concerning will be the lack of cultivation of new talented speakers and thought leaders, as access to them by industry will be a challenge. most, if not all of us, trained in an academic center as residents or even stayed on at some point in our careers as teachers…calling many of our professors “mentors” and being proud of our institutions, coveting them as badges of honor. unfortunately, as many residents are skin july 2020 volume 4 issue 4 copyright 2020 the national society for cutaneous medicine 311 denied exposure to the pharmaceutical industry out of concern for developing biased decision-making for their patients, there perpetuates the mindset which labels the very best of us as biased if we have any “conflicts of interest,” even to the point of depriving leadership positions because of the perception of guilt. the problem with the hypocrisy of bias is trying to be above one’s own bias, which doesn’t work when judgment is subjective and without proof of any violations. the main issue is the lack of mentorship for how to work constructively with industry based on one’s intention and ambitions. young dermatologists need to know who to talk to, as msels, professional relations, and medical affairs teams look to cultivate talent for speaking, research, advisory boards, and sponsored meetings, because they are the conduits for moving forward in medical education and clinical trials. take reps and all sales people out of the equation, they are usually powerless in the discussion because of the firewalls. often times they don’t know or have never met who their company’s thought leaders (spoken from experience) and, for some, their concern is the risk of “jeopardizing” future prescriptions, especially if the doctor is out on the road and not in the office because of educational or advisory work for the same company. it is also critical to prepare and update cvs, published articles, or presentation slides if there is an interest in working with industry. however, the key to the equation is to create a niche that makes industry come to find new talent, rather than the other way around. in the end, there is no proven correlation to the quantity of prescriptions written and the ability to teach, write articles, or speak at meetings. in reality, most investigators and teachers are not high-volume prescribers of any therapy, so what is the resolution of the ethical dilemma if companies want to collaborate with speaker opportunities? many of the professional relations managers in pharma are watching these trends as the virtual way of meeting and teaching continues to progress, and some have been pleased with what they see. for example, while on camera it is a lot harder for advisors if we get invited to be distracted on the phone texting or sitting like a zombie not saying a word. however, the lack of in-person meetings does not help to cultivate new talent or meet someone new. which, in turn, does not help the new dermatologist who wrote a lecture on a subject and did not get a chance to present it at an uncompensated cme meeting. so, is this a lost chance to meet an expert? unfortunately, we are all being pulled down paths of increased political correctness, where guilt is not only presumed it is often accepted without a rational basis. there it is again, the institutional bias against those who are perceived as biased… which is hypocrisy. in summary, the new normal for the virtual world of pharma can have significant upsides. for example, redistribution of the money on airfare, hotels, and meeting expenses by employees and physicians in favor of virtual advisory and investigator meetings can result in more support for dermatology meetings that will soon reconvene. more patient initiatives can sprout from funding that otherwise could not due to inefficiency in spending. as for the pharma sales reps, i for one want to streamline their jobs and make them more efficient and therefore more valued. a better experience for them and the clinic staff can be developed which still promotes sales, and a smarter use of time can lead to better outcomes for everyone including patients. so, buckle up everyone, and get ready for the new pharma coming soon to an office near you. conflict of interest disclosures: none funding: none corresponding author: neal bhatia, md director, clinical dermatology therapeutics clinical research 9025 balboa avenue, suite 105 san diego, ca 92123 phone: 858-571-6800 fax: 858-571-6801 email: bhatiaharbor@gmail.com skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 41 brief articles a case of granulomatous hypersensitivity reactions to a dermal filler precipitated by pd-1 checkpoint inhibitor therapy parneet k. dhaliwal, do, ms1, sidra ibad, ms22, diana losak, pa-c1, clay j. cockerell, md, mba4 1baylor university medical center, dallas, tx 2icahn school of medicine at mount sinai, new york, ny 3cockerell dermatopathology, dallas, tx 4ut southwestern, dallas, tx dermal filler injections have grown rapidly in popularity over the last decade. they provide an effective way of improving the appearance of individuals with rhytides and tissue loss secondary to skin aging.2,3 while the vast majority of these injections are accomplished without complication, foreign body reactions may develop in 0.04%-0.3% of bovine collagen injection cases. factors influencing these reactions include filler material impurities, procedural techniques, and co-existing systemic infections and concurrent medications or immunotherapy. foreign body reactions are host responses that develop to remove foreign material and repair surrounding tissue. this reaction is a part of the inflammatory and wound healing process that may develop when patients have surgical implantation of prosthesis, placement of medical devices, or injection of biomaterials.4 they are also seen in response to dermal fillers, of which hyaluronic acid and collagen are most common.4 foreign body granulomatous inflammation involves five phases: abstract injection of filler material has become a routine procedure in dermatology practices in an attempt to improve the appearance of rhytides and prevent skin volume loss associated with aging. while the vast majority of injections are performed without complications, foreign body reactions may develop in 0.04-0.3% of individuals who receive fillers1. we recently encountered a 65-year-old woman with recurrent malignant melanoma who presented with a 2 month history of marked thickening of the skin along the sides of her face. she had been receiving nivolumab infusions for recurrent malignant melanoma and noted that these symptoms worsened after each infusion. she reported undergoing cosmetic procedures three years prior, one of which was an injection of a long-lasting dermal filler, polymethylmethacrylate microsphere enhanced bovine collagen (bellafill). a biopsy of two areas revealed nodular infiltrates of histiocytes with small round lobules identified as polymethylmethacrylate microspheres. based on clinical and histopathologic findings, a diagnosis of granulomatous dermatitis filler reaction was rendered. nivolumab is a pd-1 checkpoint inhibitor that disrupts t-cell inhibitory pathways leading to increased immune activation. in this case, hyper-immune activation triggered a florid granulomatous reaction to the filler the patient had been injected with 3 years previously. this is a newly recognized side effect of pd-1 checkpoint immunotherapy and patients who are about to initiate such therapy should be warned about this potential complication. introduction skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 42 recognition of inflammation, protein adsorption, macrophage adhesion, macrophage fusion, and “crosstalk” among inflammatory cells4. the granulomas are comprised of multinucleated giant cells, tlymphocytes, histiocytes and fibroblasts.4 we recently encountered a patient who developed a florid delayed granulomatous reaction to polymethylmethacrylate microsphere enhanced bovine collagen injected 3 years prior to receiving therapy with a pd-1 checkpoint inhibitor for malignant melanoma. a 65-year old caucasian woman with a 2 month history of malignant melanoma presented with hardening and thickening of the skin along the sides of her face. two years prior to presentation she was diagnosed with a non-ulcerated clark's level 4, 1.25 mm malignant melanoma of the left calf. she underwent wide excision and sentinel lymphadenectomy, which was negative for metastasis. in march of 2019, two years after the malignant melanoma had been excised, she noticed discoloration proximal to the previous surgical site. a biopsy confirmed recurrence of melanoma and another wide local excision was performed. sentinel node biopsy was performed and again negative for metastasis. further work up included positron emission tomography (pet) scanning which was negative, and she was staged at t4an0m0 representing iib with recurrence. her oncologist recommended immunotherapy treatment with nivolumab. her first infusion was given in april 2019 and continued on a monthly basis. the patient noted "thickening" of the skin near the temples three weeks after the first nivolumab infusion. after each subsequent infusion, she developed additional nodules along her temples, nasolabial folds, lips, and chin which progressively became more painful and firm. cutaneous examination demonstrated firm dermal nodules around the corners of her lips and peri-orbitally. (figure 1) upon further questioning, she reported undergoing cosmetic procedures one year prior, one of which was a dermal filler injection, bellafill, comprised of bovine collagen with non-resorbable polymethylmethacrylate microspheres. she did not have any skin testing prior to these procedures and experienced no adverse reactions at the time. she denied any other cosmetic procedures since then. two of the affected areas of her face were biopsied and demonstrated a diffuse granulomatous dermatitis with exogenous filler recognizable as polymethylmethacrylate spheres within histiocytes. (figure 1) the patient was seen at follow-up by her oncologist and plastic surgeon, who both recommended continuing infusion therapy unless the foreign body reaction worsened to the point of necrosis. at her follow up visit, the dermal nodules showed spontaneous regression despite continued immunotherapy. her melanoma remained in remission. after clearance from her oncologist, she underwent 2 botulinum toxin injections for her rhytides (at her request), which resulted in no adverse reactions. nivolumab is a human immunoglobulin g4 (igg4) that is approved by the food and drug administration (fda) for treatment of various cancers including advanced melanoma.4 nivolumab blocks the interaction of pd-1 receptors with program cell death ligands pd-l1 and pd-l2, and case presentation discussion skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 43 figure 1. (a) inflammation and lichenification at previous sites of bellafil dermal injections. (b) nodular infiltrates of histiocytes with small round lobules recognizable as polymethylmethacrylate microscpheres (h&e, 10x and 20x) restores cytotoxic t-cells’ ability to destroy tumor cells.5 in this case, immune activation triggered a florid granulomatous reaction to the filler the patient received 3 years prior. nivolumab’s ability to activate t cells indirectly led to stimulation of macrophages to phagocytose filler particles that were previously non-immunogenic, leading to the formation of granulomas with multinucleated histiocytes. these cells likely reacted with tlymphocytes creating a delayed hypersensitivity immune response.6 to our knowledge, there is one similar case report of a granulomatous inflammatory reaction triggered by an immune checkpoint inhibitor in which ipilimumab therapy for malignant melanoma caused significant hilar granulomatous inflammation that simulated skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 44 sarcoidosis.9 however, that case was not related to filler injections. pd-1 inhibitors vary significantly from one another in terms of adverse reactions, and the likelihood of checkpoint inhibitors causing reactions remains unclear. common side effects impact the skin and thyroid, while ctla-4 inhibitors have been linked to gi symptoms. in one case report, nivolumab treatment was linked with facial flushing and dyspnea, while pembrolizumab caused no reactions in the same patient6. ipilimumab, a ctla-4 inhibitor, can cause similar adverse reactions as nivolumab. therefore, it can be difficult to predict what type of adverse reaction a patient will have. in a cross-sectional study, hyaluronic acid (ha) fillers were associated with infection and swelling, making up approximately 84.2% of the total 0.01% complication rate for all ha filler injections8. ha based fillers have a disproportionately higher rate of infection than was predicted. however, studies suggest that patients were diagnosed with infection prematurely and complications were largely a result of breaking sterile protocol and procedural techniques. alternately, bellafill fillers were often accompanied by nodule formation, comprising 40% of the 0.01% complication rate. ha has been considered the preferable option due to its lower viscosity, greater withdrawal with injection, and capability for reversal with hyaluronidase. bellafill, consists of bovine collagen and pmma microspheres, which have lower withdrawal with injection and serve as a signal to the body to produce more collagen, rather than a natural replacement for collagen7. in our patient, the lesions spontaneously resolved over time even though the infusions continued. while intralesional injections with corticosteroid might have been effective, it was not necessary. the reason the inflammation abated spontaneously is however unknown. some of the known adverse reactions to pd-1 inhibitors include morbilliform eruptions, erythematous plaques, bullous dermatoses, psoriasiform dermatitis and now, granulomatous inflammation at sites of prior dermal filler injections. a prior history of melanoma and rapid development of nodules in our patient raised concern for dermal metastases, which fortunately was excluded by biopsy. clinicians should be wary of this phenomenon and counsel patients about the possibility of its development before initiating an immune checkpoint inhibitor. a thorough history, including previous cosmetic procedures, can help to avoid potential complications during immune checkpoint therapy. while our patient’s reaction spontaneously resolved, this may not always be the case. hyper-immune activation is a recognized complication of pd-1 checkpoint immunotherapy. given the prevalence of cosmetic injections, dermatologists must consider a dermal filler related granulomatous reaction in patients that develop nodules while being treated with checkpoint inhibitors. conflict of interest disclosures: none funding: none corresponding author: parneet k. dhaliwal, do, ms baylor university medical center at dallas roberts hospital, suite 1013 3500 gaston ave. dallas, tx 75246 email: parneet.dhaliwal@bswhealth.org conclusion skin january 2021 volume 5 issue 1 copyright 2021 the national society for cutaneous medicine 45 references: 1. lee, j. m., & kim, y. j. (2015). foreign body granulomas after the use of dermal fillers: pathophysiology, clinical appearance, histologic features, and treatment. archives of plastic surgery, 42(2), 232–239. https://doi.org/10.5999/aps.2015.42.2.232 2. rzany b, hilton s, prager w, et al. expert guideline on the use of porcine collagen in aesthetic medicine. j dtsch dermatol ges. 2010;8(3):210–217. 3. goldberg dj. legal ramifications of off-label filler use. dermatol ther. 2006;19(3):189‐193. doi:10.1111/j.1529-8019.2006.00073.x 4. lee jm, kim yj. foreign body granulomas after the use of dermal fillers: pathophysiology, clinical appearance, histologic features, and treatment. arch plast surg. 2015;42(2):232–239. doi:10.5999/aps.2015.42.2.232 5. nivolumab. in: micromedex solutions [online database], ann arbor, mi: truven health analytics. accessed 2020. may 31. 6. hibler bp, yan by, marchetti ma, momtahen s, busam kj, rossi am. facial swelling and foreign body granulomatous reaction to hyaluronic acid filler in the setting of tyrosine kinase inhibitor therapy. j eur acad dermatol venereol. 2018;32(6):e225‐e227. doi:10.1111/jdv.14749 7. choi b, mcbride a, scott aj. treatment with pembrolizumab after hypersensitivity reaction to nivolumab in a patient with hepatocellular carcinoma. am j health syst pharm. 2019;76(21):1749‐1752. doi:10.1093/ajhp/zxz189 8. rayess, h. m., svider, p. f., hanba, c., patel, v. s., dejoseph, l. m., carron, m., & zuliani, g. f. (2018). a cross-sectional analysis of adverse events and litigation for injectable fillers. jama facial plastic surgery, 20(3), 207–214. https://doi.org/10.1001/jamafacial.2017.1888 9. chorti e, kanaki t, zimmer l, et al. drug-induced sarcoidosis-like reaction in adjuvant immunotherapy: increased rate and mimicker of metastasis. eur j cancer. 2020;131:18‐26. doi:10.1016/j.ejca.2020.02.024 powerpoint presentation poster #12797safety of long-term proactive management with fixed-dose combination calcipotriene 0.005% and betamethasone dipropionate 0.064% foam in patients with psoriasis vulgaris: results of a phase iii, multicentre, randomized, 52-week, vehicle-controlled trial mark lebwohl1, jean-philippe lacour2, monika liljedahl3, charles lynde4,5, marie holst mørch3, diamant thaçi6 and richard b warren7 1department of dermatology, icahn school of medicine at mount sinai, new york, ny, usa; 2department of dermatology, university hospital of nice, nice, france; 3leo pharma a/s, ballerup, denmark; 4lynde dermatology, probity medical research, markham, on, canada; 5department of medicine, university of toronto, toronto, on, canada; 6institute and comprehensive center for inflammation medicine, university of lübeck, lübeck, germany; 7dermatology centre, salford royal nhs foundation trust and nihr biomedical research centre, university of manchester, manchester, uk materials and methods introduction  topical therapies are considered first-line treatment for psoriasis,1 however maintaining long-term disease control is a challenge, with many patients untreated or undertreated.2 current topical psoriasis treatment relies on a reactive approach to disease flares, as opposed to a more long-term proactive approach.3  data supporting the efficacy and safety of calcipotriene 0.005% and betamethasone dipropionate 0.064% (cal/bd) foam approved as a reactive treatment are available from trials of 4and 12-weeks duration in patients with psoriasis vulgaris (plaque psoriasis).4,5,6,7  here, we report the safety of cal/bd foam for the long-term proactive management of psoriasis over 52 weeks (nct02899962). data from the open-label lead-in phase of this trial are presented in poster #16830. presented at aad annual meeting 2020, denver, colorado, usa, march 20–24, 2020 references 1. feldman, et al. am health drugs benefits. 2016:9;504‒513; 2. armstrong, et al. jama dermatol. 2013:149;1180‒1185; 3. bonnekoh, et al. emj dermatol. 2017:5;36‒43; 4. emc. enstilar summary of product characteristics 2018; 5. fda. enstilar prescribing information 2019; 6. paul, et al. j eur acad dermatol venereol. 2017:31;119‒126; 7. koo, et al. j dermatolog treat. 2016:27;120‒127 acknowledgements the authors thank the investigators and patients who participated in this trial. the authors would like to thank lauren whyte, phd, a freelance medical writer contracted by ashfield healthcare communications, part of udg healthcare plc, for medical writing support, funded by leo pharma in accordance with good publications practice (gpp3) guidelines (http://www.ismpp.org/gpp3). disclosures all authors met the icmje authorship criteria and had full access to the relevant data. neither honoraria nor payments were made for authorship. ml, j-pl, dt, rbw, cl have consulted for, conducted studies funded by, or received honoraria for services provided to leo pharma; ml, mhm are employees of leo pharma. fixed-dose combination calcipotriene (cal) 0.005%/betamethasone dipropionate (bd) 0.064% aerosol foam is approved for the treatment of psoriasis vulgaris (plaque psoriasis) for up to 4 weeks in adults (under the trade name enstilar® in the us and enstilar® or enstilum® in the eu). cal/bd foam is also approved in the us for adolescents 12–18 years. funding this study was funded by leo pharma. safety objectives and endpoints  to evaluate the long-term safety of proactive management with cal/bd foam (up to 52 weeks) in patients with psoriasis. safety endpoints included: ─ adverse events (aes) associated with long-term corticosteroid use. ─ incidence of rebound (see table 3 for definition). ─ effect on calcium metabolism based on serum/urinary calcium. ─ effect on hpa-axis based on serum cortisol.  this phase iii, multicenter trial included a 4-week open-label lead-in phase in adult patients with: ─ trunk and/or limb psoriasis, involving 2–30% of body surface area (bsa); physician’s global assessment (pga) of disease severity ≥’mild’; modified psoriasis area and severity index (mpasi) ≥2.  following the open-label lead-in phase, patients with treatment success (pga score of ‘clear’ or ‘almost clear’ [pga<2] with at least a 2-grade improvement from baseline) were randomized to the 52-week double-blind, vehicle-controlled maintenance phase.  the trial included a subgroup of patients at assigned sites who underwent hypothalamic pituitary adrenal (hpa) testing. the hpa-axis group was required to have more severe disease: ─ at least ‘moderate’ psoriasis, affecting 10–30% bsa and normal adrenal function at baseline. results patient population  545 patients were randomized (safety analysis set [sas]; proactive n=272; reactive n=273). 251 (46.1%) patients completed the trial. mean age was 52.2 years; 91% patients were white and 68% were male. aes during maintenance phase table 1. overview of aes aes adjudicated as associated with long-term corticosteroid use in maintenance phase  chorioretinopathy in one patient: severe intensity, onset on day 310, considered possibly related to treatment by investigator, led to withdrawal of treatment [proactive].  pain of skin in one patient: moderate intensity, onset on day 73, not considered related to treatment by investigator, no action taken with treatment [proactive].  application site pain in one patient: 3 events of mild intensity, onset on days 1, 12 and 20, considered probably related to treatment by investigator, no action taken with treatment [reactive]. rebound other safety results  no consistent changes or differences in serum or urinary calcium between the two treatment groups. ─ no difference in the number of patients moving from low or normal to high calcium or from normal or high to low calcium in either serum or urine. most patients had levels that remained stable over time. ─ no clinically significant abnormalities in calcium metabolism were observed.  in the hpa-axis group, no patient had serum cortisol ≤18 µg/dl at both 30 and 60 min after acth challenge. 1considered possibly or probably related to trial product by the investigator conclusions  proactive management with cal/bd foam was well tolerated, with a favorable safety profile over the extended treatment period that was similar to the vehicle-controlled reactive treatment group.  proactive management with cal/bd foam had no clinically significant effects on the hpa-axis or calcium metabolism. table 3. summary of rebounds* trial design and treatments table 2. rate of aes per 100 patient-years double-blind treatment  ‘proactive’ management was treatment with cal/bd foam twice-weekly for 52 weeks when in remission.  ‘reactive’ management was treatment with vehicle foam twice-weekly for 52 weeks when in remission.  relapse: pga≥2 [either previously treated and/or new skin area]). flare medication (as separate flare bottles) was cal/bd foam once-daily for 4 weeks for both the proactive and reactive management groups (figure 1). primary objective  efficacy objectives, endpoints and data are presented in poster #18223. *rebound defined as i) m-pasi ≥12 and increase from baseline in m-pasi ≥125% or ii) development of more inflammatory disease within 2 months after discontinuation of open-label, maintenance or flare medication. most frequently reported aes  aes reported in >5% of patients: nasopharyngitis (8.1% proactive vs 7.0% reactive) and upper respiratory tract infection (5.9% vs 5.5%); all were considered not related to trial product by the investigator. ae category proactive (n=272) reactive (n=273) number of aes number (%) of patients number of aes number (%) of patients all aes 303 133 (48.9) 279 130 (47.6) serious aes 15 14 (5.1) 14 11 (4.0) treatmentrelated aes1 5 5 (1.8) 8 7 (2.6) aes leading to withdrawal 2 2 (0.7) 1 1 (0.4) severe aes 8 8 (2.9) 15 14 (5.1) number of rebounds within 2 months proactive (n=272) reactive (n=273) after discontinuation of open-label treatment 6 7 after discontinuation of relapse treatment 4 17 after discontinuation of proactive management 0 1 proactive (n=272) reactive (n=273) aes per 100 patient-years 168.6 158.4 serious aes per 100 patient-years 8.3 7.9 treatment-related aes per 100 patient-years 2.8 4.5 figure 1. trial design screening & washout (up to 4 weeks) maintenance phase followup for 8 weeks 1 0 2 4 3 8 4 12 5 16 6 20 7 24 8 28 9 32 10 36 11 40 12 44 13 48 14 52 15 56 fu1 58 fu2 60 fu3 64 visit week cal/bd foam once daily for 4 weeks* relapse (pga ≥2) 1:1 randomizationbaseline end of maintenance phase follow-up for rebound adults with plaque psoriasis * success following 4 weeks of once daily flare medication was defined as pga<2 (‘clear [0]’ or ‘almost clear’ [1]) ** patients re-started the twice-weekly maintenance according to the original randomization scheme. pga<2** pga ≥2 withdrawn open-label lead-in phase cal/bd foam daily for 4 weeks proactive management: cal/bd foam twice weekly for 52 weeks reactive management: vehicle foam twice weekly for 52 weeks  one patient in each group had an ae of pigmentation disorder considered possibly related to trial product by the investigator. no aes of skin atrophy were reported. figure 2. patient disposition entered open-label lead-in phase (n=650) discontinued (n=105) • adverse event (n=2); lost to follow-up (n=9); w ithdrawal by patient (n=11); lack of efficacy (n=4); patient did not achieve treatment success at end of open-label lead-in phase (n=68); failed screening (n=1); other (n=10) proactive management (n=272 sas [n=256 fas]) reactive management (n=273 sas [n=265 fas]) completed the trial (n=251 sas [n=246 fas]) discontinued (n=141 sas) • adverse event (n=2); lost to follow-up (n=12); w ithdrawal by patient (n=30); lack of efficacy (n=20); patient did not achieve treatment success after open-label lead-in phase (n=3); other (n=9); patient not clear or almost clear (pga<2) after treatment of relapse (n=65). discontinued (n=153 sas) • adverse event (n=1); death (n=1); lost to follow-up (n=14); w ithdrawal by patient (n=36); lack of efficacy (n=16); patient did not achieve treatment success after open-label lead-in phase (n=2); other (n=13); patient not clear or almost clear (pga<2) after treatment of relapse (n=70). experienced at least one relapse (n=210 fas) experienced at least one relapse (n=237 fas) randomized into maintenance phase (n=545 sas [n=521 fas]) randomized in error* (n=24 [16 proactive and 8 reactive]) completed (n=5) discontinued (n=19) *excluded from full analysis set (fas) the safety analysis set (sas) included all patients exposed to cal/bd foam or vehicle foam following randomization. the fas included all randomized patients who had treatment success at randomization. slide number 1 microsoft word september 2020 idr 959 proof returned.docx skin september 2020 volume 4 issue 5 copyright 2020 the national society for cutaneous medicine 395 in-depth review topical zinc may augment post-operative wound healing, including following mohs micrographic surgery: a review of the literature nicole levin, bs1,2, taylor gray, do2, maheera farsi, do3, david dorton, do2, richard miller do2 1charles e. schmidt college of medicine, florida atlantic university, boca raton, fl 2hca healthcare/usf morsani college of medicine gme programs, largo medical center, largo, fl 3univeristy of florida college of medicine, gainesville, fl the use of zinc has been studied for the treatment of many dermatologic conditions including warts, inflammatory dermatoses like acne vulgaris and rosacea, and pigmentary disorders like melasma and neoplasms.1 zinc supplementation also reduces the risk of bacterial, viral, and fungal infections.2-4 its efficacy has been demonstrated in the setting of cutaneous healing following burn injuries5-7 and as a protectant against uv radiation in the form of abstract background: zinc, an essential mineral, has been extensively studied in the field of dermatology for the treatment of a plethora of skin conditions. however, minimal literature exists regarding its use for the enhanced healing of wounds after surgery, including following mohs micrographic surgery (mms). objective: evaluate the available literature regarding the utilization of zinc for enhanced healing of post-surgical wounds in humans. methods: a systematic review of studies evaluating the use of zinc for post-surgical management was conducted via an electronic literature search of the pubmed database. clinical trials were searched using clinicaltrails.gov. results: topical zinc formulations may decrease healing time and post-operative infection rates, including following mms of the lower extremity. limitations: currently, there are a limited number of studies available on this topic, with lack of a standard comparable outcome measure. conclusion: topical zinc oxide may be a beneficial treatment option for post-surgical wound healing, including after mms. further studies are needed to better define the efficacy of zinc for post-operative wound healing and the optimal treatment regimen. introduction skin september 2020 volume 4 issue 5 copyright 2020 the national society for cutaneous medicine 396 topical zinc oxide. additionally, zinc deficiency is associated with impaired wound healing and existing evidence supports the use of topical zinc oxide and oral zinc sulfate for the healing of leg ulcers.8-12 zinc is required for optimal activity of numerous enzymes and serves a critical role in the development and proper functioning of the immune system.13 it contributes to protein structure and the regulation of gene expression.8 it also influences gene transcription at several levels through histone deacetylation reactions and zinc-finger motifs. this essential mineral is found in some foods, including beef, poultry, seafood, and grains.8 oral formulations are also available as zinc gluconate, zinc sulfate, and zinc acetate.14 furthermore, zinc can be administered as an intravenous zinc chloride solution, generally as an addition to total parenteral nutrition.15 currently, minimal literature exists regarding the use of zinc for the healing of post-surgical wounds in humans, especially after dermatologic surgery. however, the efficacy of zinc for post-operative healing has been well documented in animal studies. studies with zinc-deficient rats demonstrated delayed epithelialization of wounds as well as a decrease in tensile strength of the resultant scars.16,17 zinc has also been shown to be beneficial for zinc-sufficient rats with a significant increase in re-epithelialization of surgical sites treated with topical zinc.18,19 bovine studies demonstrated similar results with a substantially decreased rate of skin regeneration following surgery in zinc deficient subjects as well as enhanced reepithelialization of partial-thickness wounds in nutritionally balanced subjects treated with topical zinc oxide.20,21 the purpose of this review is to evaluate the currently available literature regarding the utilization of zinc for enhanced post-surgical wound healing, including after mohs micrographic surgery (mms). a systematic review of studies describing the use of zinc for post-surgical management was performed. we conducted an electronic literature search of pubmed database on zinc and post-surgical management twice—in may and june 2020. additionally, clinical trials were searched using clinicaltrails.gov. our search yielded eight studies that have been performed on human subjects. two of these studies focused on the use of zinc oxide compression dressings for postoperative defects following lower extremity mms.22,23 efficacy of zinc for post-operative healing in 2006, a randomized, double-blind, placebo-controlled study compared the use of 3% zinc oxide mesh with placebo mesh on the healing of acute open wounds following pilonidal cyst excision.24 the 3% zinc oxide mesh provided sustained release of bioavailable zinc to the wound at noncytotoxic levels. 25-27 the results of this study demonstrated a trend toward decreased average healing time compared with placebo (54 days vs 62 days;) and a statistically significant decrease in the occurrence of staphylococcus aureus in wounds (p < 0.05). as a result, significantly fewer zinc-oxide treated patients were prescribed systemic antibiotics postoperatively (p = 0.005).24 importantly, there were no local or systemic adverse effects observed in the zinc oxide group.24 methods results skin september 2020 volume 4 issue 5 copyright 2020 the national society for cutaneous medicine 397 administration of oral zinc sulfate has been shown to enhance the rate of wound healing in venous leg ulcers,11,12 sickle-cell ulcers,28 and pressure ulcers.29 one study investigated the effects of oral zinc sulfate in the healing of surgical wounds caused by the removal of pilonidal-sinus tracts.30 average wound volume was 32.3 ml in the control group and 54.4 ml in the treatment group. ten participants ingested 220 mg of zinc sulfate daily while ten controls did not. the healing rate was significantly increased in the zinc-medicated group, with wound closure occurring almost three times faster than the control group (p < 0.02).30 aesthetics also differed between the two groups as it was noted that the wounds in the zinc-medicated group appeared cleaner, pinker, and healthier with less purulent exudate when compared to the wounds in the control group. 30 no toxic side effects were noted during the 61 days in which the patients were followed.30 a similar study failed to produce the same results.31 the authors speculate that varying results were seen because oral zinc sulfate may not play a significant role in wound healing, or possibly, that neither study was sufficiently controlled to account for variations among individual patients.31 the parenteral administration of zinc gluconate was analyzed by faure et. al in a double-blind, randomized study of 30 patients who underwent major reconstructive surgery for the treatment of abdominal aorta atherosclerosis.32 15 patients received a 30 mg iv drip of zinc gluconate for 3 days, while the control group received a placebo.32 no healing complications were reported in the zinc-medicated group.32 however, 4 of 15 patients in the placebo group experienced complications including delayed wound healing, lymphorrhea, and inflammation (p = 0.00771).32 weingert and stoll compared the efficacy of topical zinc oxide ointment and potassium/calcium chloride hydrogel on the epithelialization of split thickness skin graft donor sites from which grafts were harvested for use in oral and maxillofacial surgery. donor sites were located on the upper thigh and demonstrated complete epithelialization more rapidly when treated with zinc oxide (8.7 days vs 10.7 days).33 furthermore, patients in the zinc oxide group did not have any subjective complaints. in contrast, transient burning was reported in 14 patients treated with the potassium/calcium chloride hydrogel. 14 months after grafting, no aesthetic differences were noted between the two groups.33 efficacy of zinc for post-operative healing in mohs micrographic surgery in 2011, stebbins et al. utilized unna boots, a compression dressing consisting of gauze bandages soaked with zinc oxide, for postoperative mms wound care in 10 patients.22 the defect size ranged from 3.6 to 30 cm2 and wound depth varied between subcutaneous fat and muscle. this study demonstrated significant granulation tissue development in the first post-operative week of all subjects and an average time to complete epithelialization of 7.1 weeks with a range of 4 to 12 weeks.22 no subjects in this study developed excess granulation tissue or post-operative infection, and all patients reported high satisfaction with this intervention.22 the occlusion provided by the unna boot may enhance wound healing independently or by augmenting the antibacterial and anti-inflammatory properties of zinc, as occluded wounds have been shown to heal four to five times more quickly than non-occluded wounds.34-37 in 2017, a retrospective cohort study compared standard post-operative wound care to zinc oxide compression dressings for skin september 2020 volume 4 issue 5 copyright 2020 the national society for cutaneous medicine 398 surgical sites on the legs, a particularly challenging area to manage in the postoperative period that is often complicated by delayed healing, dehiscence, hematoma, and infection.22,23 the average incision length was 4.35 cm in the group receiving standard dressing and 6.35 cm in the zinc-oxide treated group. standard wound care included applying petroleum jelly to the post-operative site followed by nonadherent dressing, gauze, and paper tape. the patients who received the standard wound care were instructed to leave the dressing in place for 48 hours following initial application and then to clean the wound, apply petroleum jelly, and change the dressing on a daily basis. the patients who received the zinc oxide compression bandage did not perform any wound care at home but returned to the office weekly for a bandage change. they were instructed to return for at least two weeks or until epithelialization of the wound was achieved. at 19 days, 91.7% of patients receiving the zinc oxide compression bandage were fully healed, whereas only 65.9% of patients receiving standard wound care were healed (p < 0.001).23 furthermore, no complications occurred in the zinc oxide group; however, 6 complications were noted in the group receiving standard wound care, including infection, wound dehiscence, postoperative bleeding, pain, and excessive swelling.23 currently a clinical trial is in progress which will compare scar outcomes following dermatologic surgery when treated with topical zinc oxide versus petrolatum.38 this split-scar study will treat half of the incision with zinc oxide and half with petrolatum. this is the first clinical trial studying the use of zinc oxide in the post-surgical setting which will analyze its results through the use of the patient and observer scar assessment scale (posas) scoring system. zinc in the integumentary system zinc is a trace element essential for many aspects of health. it serves as a cofactor for enzymes required for cellular replication, protein synthesis and repair systems as well as transcription factors.39 specifically, zincfinger proteins are a family of over 2,000 transcription factors that interact with dna and rna polymerases to initiate transcription of key genes for wound healing.39,40 specific zinc-finger transcription factors identified in the skin include basonuclin, an important mediator of cellular division, and c-krox, a vital protein that controls expression of genes that encode the extracellular matrix (ecm).40 zinc is also involved in intracellular signaling and neurotransmission.39 in the integumentary system, zinc plays a role in mitosis, migration and maturation of keratinocytes. it is found in the form of protein complexes intracellularly and in the ecm.39 while zinc is found in both epidermal and dermal tissues, concentrations in the epidermis are higher, potentially reflecting the activity of zinc-dependent rna and dna polymerases in the mitotically active basal cells.39 furthermore, an inverse relationship is observed in the epidermis between the zinc concentration and the state of maturation and keratinization of post-mitotic cells.39 for example, as keratinocytes mature and reach the corneal layer, zinc levels are lower than in the mitotically active basal layer. the role of zinc in wound healing wound healing can be characterized by three phases: inflammatory phase, proliferative phase, and remodeling phase. the inflammatory phase starts within hours of tissue injury and may last 3-4 days.41 during the inflammatory phase hemostasis is achieved by platelets and a fibrin matrix discussion skin september 2020 volume 4 issue 5 copyright 2020 the national society for cutaneous medicine 399 table 1. studies of zinc therapy for post-operative wound healing which serve as the initial scaffold for infiltrating cells.40,41 before the cessation of the inflammatory phase, neutrophils and macrophages phagocytize debris and debride the tissue.40,41 the proliferative phase of healing begins 2-10 days after injury and is characterized by mitotic activity and migration of keratinocytes, blood vessels, and fibroblasts.41 during this phase, the keratinocytes at the leading edge of the wound proliferate and mature.41 the remodeling phase begins approximately 3 weeks following tissue injury and can last for more than one year.41 matrix title study type subject information route of zinc administration comparison conclusion enhanced healing of surgical wounds of the lower leg using weekly zinc oxide compression dressings 22 observational 10 patients 6 male, 4 female age range: 72-91 topical zinc oxide compression bandage n/a average time to complete epithelialization of 7.1 weeks with a range of 4 to 12 weeks effect of postoperative dressing on excisions performed on the leg: a comparison between zinc oxide compression dressings versus standard wound care 23 retrospective cohort 80 patients 16 male, 54 female age range: 19-89 topical zinc oxide compression bandage zinc oxide compression dressing (n=36) vs standard dressing (n=44) zinc oxide compression dressings resulted in decreased incidence of delayed wound healing with fewer complications compared to standard postoperative wound dressing group (p < 0.001) a randomized, double-blind, placebo-controlled multicenter trial evaluating topical zinc oxide for acute open wounds following pilonidal disease excision 24 randomized, double-blind placebocontrolled trial 64 patients 53 male, 11 female age range: 17-60 topical zinc oxide mesh 3% zinc oxide mesh (n=33) vs placebo mesh (n=31) zinc oxide decreased the average healing time and decreased the occurrence of staphylococcus aureus in wounds (p < 0.05) acceleration of wound healing in man with zinc sulfate given by mouth 30 randomized control trial 20 patients 20 male, 0 female age range: 18-40 oral 220 mg zinc sulfate tid control (n=10) vs 220 mg zinc sulfate tid (n=10) post-surgical wounds in the zinc-medicated patients closed three times faster compared to the control group (p < 0.02) lack of acceleration of healing with zinc sulfate 31 randomized control trial 20 patients age range: 19-35 oral 220 mg zinc sulfate tid control (n=10) vs 220 mg zinc sulfate tid (n=10) no acceleration of wound healing was found in young patients with granulating wounds given oral zinc sulfate versus the control group parenteral supplementation with zinc in surgical patients corrects postoperative serum-zinc drop 32 double-blind, randomized study 30 patients parenteral iv zinc gluconate iv zinc gluconate 30 mg/day for 3 days (n=15) vs placebo (n=15) clinical inspection of wounds following complicated surgery revealed that zinc supplementation was beneficial even if serum zinc was normal before intervention (p = 0.00771) the epithelialization of split skin graft donor sites a test model for the efficacy of topical wound therapeutic agents 33 prospective, clinical study 16 patients 6 male, 10 female age range: 18-81 topical zinc oxide ointment zinc oxide ointment (n=16) vs potassium/calcium chloride hydrogel (n=16) more rapid epithelialization was observed in zinc oxide group zinc oxide versus petrolatum following skin surgery: a head-to-head, prospective, split-scar study 38 comparative 30 patients topical zinc oxide ointment zinc oxide ointment (n=30) vs petrolatum (n=30) study currently in progress skin september 2020 volume 4 issue 5 copyright 2020 the national society for cutaneous medicine 400 metalloproteinases (mmps) have the vital job of remodeling the scar.40,41 zinc and zinc-containing proteins are involved in nearly every aspect of cutaneous wound repair. metallothioneins (mts) bind approximately 20% of intracellular zinc and are responsible for transporting zinc to enzymes and gene-regulatory molecules important for wound healing.39,40 mts can be thought of as surrogate markers for zinc. spectrometry and immunohistochemical techniques have been utilized to demonstrate that mts are expressed at higher rates in healing wounds than in normal skin.39,40 treatment of keratinocytes in vitro with zinc chelators has been shown to inhibit upregulation of mts and cellular proliferation.40 conversely, mt upregulation can be induced in vivo by exposure to zinc.40 collectively, these findings show that the requirement for zinc is higher in skin during times of healing and that zinc induces the expression of mts that serve an important role in its storage and transportation. mmps are a diverse group of zinc-dependent enzymes that play an important role in wound healing. mmps are up-regulated following injury and are crucial for wound debridement, cell migration, and reconstitution of the ecm.39,42 this has been demonstrated by the fact that synthetic mmp inhibitors result in impaired keratinocyte migration and wound contraction.39,43,44 mmps with notable action in wound healing include mmp-1, mmp-9, mmp-14, and mmp-2. mmp-1 has a primary role in initiating tissue repair and epithelization.39 elevated levels have been demonstrated in 24-hour human fibroblasts and in migrating epidermal cells during the acute phase of healing.39,43,44 mmp-9 and mmp-14 are likely involved in keratinocyte migration while mmp-2 is persistent in fibroblasts and endothelial cells throughout the wound healing process and is primarily involved in ecm remodeling.39 keratinocyte migration is also modulated by zinc through the expression of integrins. in healthy skin, integrins are expressed primarily in the basal layer and promote intercellular and cell to basement membrane adhesion.39 supplementary zinc during wound healing promotes induction of key integrin subunits that enhance keratinocyte motility.39,45 as well as acting on specific proteins important for wound healing, zinc enhances intracellular mitogenic signaling pathways to up-regulate endogenous growth factors that can contribute to epithelialization.39 furthermore, zinc plays a significant role in inflammation reduction.40 alkaline phosphatase (ap) is one zinc-dependent enzyme that regulates inflammation.40 ap is released from the surface of epithelial cells and dephosphorylates adenosine monophosphate (amp) to make adenosine, which has anti-inflammatory action and helps to curtail the initial inflammatory phase of wound healing.40 practical implications for the utilization of zinc in the post-operative period most studies evaluating the efficacy of zinc in wound healing have been conducted on patients with chronic wounds. these studies have failed to show a statistically significant benefit for oral zinc supplementation, unless there is clinical evidence of low serum zinc.39,46 furthermore, a recent review of dietary supplements in dermatology demonstrated that there is not enough evidence at this time to justify the use of oral zinc supplementation for the purpose of wound healing.47 this, combined with potential adverse events associated with oral zinc supplementation, most notably gastrointestinal discomfort, may suggest that skin september 2020 volume 4 issue 5 copyright 2020 the national society for cutaneous medicine 401 topical zinc therapy is better suited to augment healing in the post-operative period.39,48 when choosing a topical zinc formulation, it is important to consider bioavailability and potential adverse effects. soluble salts may be irritating, while less soluble options like zinc oxide are not. zinc oxide formulations have been used for a wide array of dermatologic manifestations for many years with an excellent safety profile, and have been shown to effectively augment wound healing.19,22,23,40 while it may occasionally cause burning, stinging, itching, and tingling when utilized on inflamed tissues, hypersensitivity to topical zinc oxide is rare, and a clinical picture of contact allergy should cause the physician to evaluate components of the zinc delivery method.39,34 zinc oxide hydrolyzes on the acidic skin surface to release the biologically active zn2+. agren demonstrated that zinc oxide in a rosin-based occlusive dressing applied to normal human skin lead to accumulation of zinc in the corneal layer and deeper layers after longer exposure,49 however, zinc oxide penetration has not been proven by occlusive hydrocolloid adhesive dressings or microfine zinc oxide.49,50 despite these findings, recent studies have demonstrated enhanced healing of surgical wounds with use of zinc oxide compression dressings.22,23 this information, coupled with beneficial properties of compression for wound healing, may make zinc oxide compression dressings an alternative treatment option for standard wound care in the post-operative setting, particularly for high-risk regions such as lower extremities. for patients who do not require compression but would benefit from enhanced wound healing and decreased risk of infection, zinc oxide ointment may represent a convenient and affordable alternative to commonly used petroleum jelly. while there is a paucity of data regarding topical zinc for post-operative wound healing in the field of dermatology, studies to date have demonstrated promising results for its use in the healing of post-operative wounds.22-24,33 the use of zinc may be considered for patients after mms to help facilitate wound healing and decrease risk of infection. topical zinc may be a safe and affordable therapy in the post-operative period, with subsequent dressing, including after flaps, grafts, and secondary intention healing. we encourage further randomized studies to assess the utility of zinc formulations on wounds after mms. conflict of interest disclosures: this research was supported by hca and/or an hca affiliated entity. the views expressed in this publication represent those of the author(s) and do not necessarily represent the official views of hca or any of its affiliated entities. funding: none corresponding author: nicole levin, bs 777 glades road bc-71 boca raton, fl 33431 email: nlevin2019@health.fau.edu references: 1. gupta m, mahajan vk, mehta ks, chauhan ps. zinc therapy in dermatology: a review. dermatol res pract. 2014;2014:709152. 2. gammoh nz, rink l. zinc in infection and inflammation. nutrients. 2017;9(6). 3. read sa, obeid s, ahlenstiel c, ahlenstiel g. the role of zinc in antiviral immunity. adv nutr. 2019;10(4):696-710. 4. xie j, zhu l, zhu t, et al. zinc supplementation reduces candida infections in pediatric intensive care unit: a randomized placebo-controlled clinical trial. j clin biochem nutr. 2019;64(2):170173. conclusion skin september 2020 volume 4 issue 5 copyright 2020 the national society for cutaneous medicine 402 5. kurmis r, greenwood j, aromataris e. trace element supplementation following severe burn injury: a systematic review and meta-analysis. j burn care res. 2016;37(3):143-159. 6. adjepong m, agbenorku p, brown p, oduro i. the role of antioxidant micronutrients in the rate of recovery of burn patients: a systematic review. burns trauma. 2016;4:18. 7. berger mm, baines m, raffoul w, et al. trace element supplementation after major burns modulates antioxidant status and clinical course by way of increased tissue trace element concentrations. am j clin nutr. 2007;85(5):12931300. 8. saper rb, rash r. zinc: an essential micronutrient. am fam physician. 2009;79(9):768-772. 9. stromberg he, agren ms. topical zinc oxide treatment improves arterial and venous leg ulcers. br j dermatol. 1984;111(4):461-468. 10. rittenhouse t. the management of lowerextremity ulcers with zinc-saline wet dressings versus normal saline wet dressings. adv ther. 1996;13(2):88-94. 11. greaves mw, skillen aw. effects of longcontinued ingestion of zinc sulfate in patients with venous leg ulceration. lancet. 1970;2(7679):889891. 12. hallbook t, lanner e. serum-zinc and healing of venous leg ulcers. lancet. 1972;2(7781):780782. 13. prasad as. zinc in human health: effect of zinc on immune cells. mol med. 2008;14(5-6):353357. 14. nih. zinc fact sheet for health professionals. https://ods.od.nih.gov/factsheets/%20zinchealthprofessional/. published 2020, march 6. accessed. 15. nih. zinczinc chloride injection, solution. https://dailymed.nlm.nih.gov/dailymed/lookup.cfm ?setid=9a1914a0-e195-4233-c1bebc2075580eb8. published 2019, november 28. accessed. 16. sandstead hh, shepard gh. the effect of zinc deficiency on the tensile strength of healing surgical incisions in the integument of the rat. proc soc exp biol med. 1968;128(3):687-689. 17. agren ms, franzen l. influence of zinc deficiency on breaking strength of 3-week-old skin incisions in the rat. acta chir scand. 1990;156(10):667-670. 18. hallmans g, lasek j. the effect of topical zinc absorption from wounds on growth and the wound healing process in zinc-deficient rats. scand j plast reconstr surg. 1985;19(2):119125. 19. lansdown ab. influence of zinc oxide in the closure of open skin wounds. int j cosmet sci. 1993;15(2):83-85. 20. miller wj, morton jd, pitts wj, clifton cm. effect of zinc deficiency and restricted feeding on wound healing in the bovine. proc soc exp biol med. 1965;118:427-430. 21. agren ms, chvapil m, franzen l. enhancement of re-epithelialization with topical zinc oxide in porcine partial-thickness wounds. j surg res. 1991;50(2):101-105. 22. stebbins wg, hanke cw, petersen j. enhanced healing of surgical wounds of the lower leg using weekly zinc oxide compression dressings. dermatol surg. 2011;37(2):158-165. 23. thompson cb, wiemken tl, brown ts. effect of postoperative dressing on excisions performed on the leg: a comparison between zinc oxide compression dressings versus standard wound care. dermatol surg. 2017;43(11):1379-1384. 24. agren ms, ostenfeld u, kallehave f, et al. a randomized, double-blind, placebo-controlled multicenter trial evaluating topical zinc oxide for acute open wounds following pilonidal disease excision. wound repair regen. 2006;14(5):526535. 25. sunzel b, soderberg ta, reuterving co, hallmans g, holm se, hanstrom l. neutralizing effect of zinc oxide on dehydroabietic acidinduced toxicity on human polymorphonuclear leukocytes. biol trace elem res. 1991;31(1):3342. 26. agren ms, mirastschijski u. the release of zinc ions from and cytocompatibility of two zinc oxide dressings. j wound care. 2004;13(9):367-369. 27. agren ms, krusell m, franzen l. release and absorption of zinc from zinc oxide and zinc sulfate in open wounds. acta derm venereol. 1991;71(4):330-333. 28. serjeant gr, galloway re, gueri mc. oral zinc sulfate in sickle-cell ulcers. lancet. 1970;2(7679):891-892. 29. cohen c. zinc sulfate and bedsores. br med j. 1968;2(5604):561. 30. pories wj, henzel jh, rob cg, strain wh. acceleration of wound healing in man with zinc sulfate given by mouth. lancet. 1967;1(7482):121-124. 31. barcia pj. lack of acceleration of healing with zinc sulfate. ann surg. 1970;172(6):1048-1050. 32. faure h, peyrin jc, richard mj, favier a. parenteral supplementation with zinc in surgical patients corrects postoperative serum-zinc drop. biol trace elem res. 1991;30(1):37-45. 33. weingart d, stoll, p. the epithelialization of split skin graft donor sites —a test model for the skin september 2020 volume 4 issue 5 copyright 2020 the national society for cutaneous medicine 403 efficacy of topical wound therapeutic agents. eur j plast surg. 1993;16:22-25. 34. soderberg t, agren m, tengrup i, hallmans g, banck g. the effects of an occlusive zinc medicated dressing on the bacterial flora in excised wounds in the rat. infection. 1989;17(2):81-85. 35. fox cl, jr., rao tn, azmeth r, gandhi ss, modak s. comparative evaluation of zinc sulfadiazine and silver sulfadiazine in burn wound infection. j burn care rehabil. 1990;11(2):112117. 36. baldwin s, odio mr, haines sl, o'connor rj, englehart js, lane at. skin benefits from continuous topical administration of a zinc oxide/petrolatum formulation by a novel disposable diaper. j eur acad dermatol venereol. 2001;15 suppl 1:5-11. 37. nemeth aj, eaglstein wh, taylor jr, peerson lj, falanga v. faster healing and less pain in skin biopsy sites treated with an occlusive dressing. arch dermatol. 1991;127(11):16791683. 38. zinc oxide versus petrolatum following skin surgery. in: https://clinicaltrials.gov/show/nct03561376. 39. lansdown ab, mirastschijski u, stubbs n, scanlon e, agren ms. zinc in wound healing: theoretical, experimental, and clinical aspects. wound repair regen. 2007;15(1):2-16. 40. schwartz jr, marsh rg, draelos zd. zinc and skin health: overview of physiology and pharmacology. dermatol surg. 2005;31(7 pt 2):837-847; discussion 847. 41. gurtner gc, werner s, barrandon y, longaker mt. wound repair and regeneration. nature. 2008;453(7193):314-321. 42. ravanti l, kahari vm. matrix metalloproteinases in wound repair (review). int j mol med. 2000;6(4):391-407. 43. mirastschijski u, impola u, jahkola t, karlsmark t, ms ag, saarialho-kere u. ectopic localization of matrix metalloproteinase-9 in chronic cutaneous wounds. hum pathol. 2002;33(3):355364. 44. mirastschijski u, haaksma cj, tomasek jj, agren ms. matrix metalloproteinase inhibitor gm 6001 attenuates keratinocyte migration, contraction and myofibroblast formation in skin wounds. exp cell res. 2004;299(2):465-475. 45. tenaud i, leroy s, chebassier n, dreno b. zinc, copper and manganese enhanced keratinocyte migration through a functional modulation of keratinocyte integrins. exp dermatol. 2000;9(6):407-416. 46. wilkinson ea, hawke ci. does oral zinc aid the healing of chronic leg ulcers? a systematic literature review. arch dermatol. 1998;134(12):1556-1560. 47. thompson kg, kim n. dietary supplements in dermatology: a review of the evidence for zinc, biotin, vitamin d, nicotinamide, and polypodium. j am acad dermatol. 2020. 48. collins n. zinc supplementation: yea or nay? adv skin wound care. 2003;16(5):226-230. 49. agren ms. percutaneous absorption of zinc from zinc oxide applied topically to intact skin in man. dermatologica. 1990;180(1):36-39. 50. gamer ao, leibold e, van ravenzwaay b. the in vitro absorption of microfine zinc oxide and titanium dioxide through porcine skin. toxicol in vitro. 2006;20(3):301-307. figure. mean percent change from baseline pasi score (95% ci) by study week and week 28 pasi status category data are as observed; sample size at each study week is based on patients with non-missing data. ci, confidence interval; lte, long-term extension; pasi, psoriasis area and severity index; w28, week 28. w28 pasi 100 w28 pasi 75–89 lte start (resurface 1) w28 pasi 90–99 w28 pasi 50–75 lte start (resurface 2) -100.0 -90.0 -80.0 -70.0 -60.0 -50.0 -40.0 -30.0 -20.0 -10.0 0.0 m ea n pe rc en t ch an ge f ro m ba se lin e p a s i sc or e study week w28 pasi 100 w28 pasi 90–99 lte start (resurface2) w28 pasi 75–89 w28 pasi 50–74 lte start (resurface1) number of patients: w28 pasi 100 w28 pasi 90–99 w28 pasi 75–89 w28 pasi 50–74 91 131 79 34 91 131 79 34 91 131 79 34 81 117 63 22 82 121 63 26 85 122 70 27 84 127 70 33 83 127 75 33 86 125 76 33 86 129 78 34 89 130 79 34 91 130 78 34 90 131 78 34 91 131 79 34 90 129 78 34 89 128 75 33 91 131 79 34 91 131 79 34 91 130 79 34 91 131 79 34 start (resurface 2) start (resurface 1) -100.0 -90.0 -80.0 -70.0 -60.0 -50.0 -40.0 -30.0 -20.0 -10.0 0.0 m ea n pe rc en t ch an ge f ro m ba se lin e p a s i sc or e study week w28 pasi 100 w28 pasi 90–99 lte start (resurface2) w28 pasi 75–89 w28 pasi 50–74 lte start (resurface1) number of patients: w28 pasi 100 w28 pasi 90–99 w28 pasi 75–89 w28 pasi 50–74 91 131 79 34 91 131 79 34 91 131 79 34 81 117 63 22 82 121 63 26 85 122 70 27 84 127 70 33 83 127 75 33 86 125 76 33 86 129 78 34 89 130 79 34 91 130 78 34 90 131 78 34 91 131 79 34 90 129 78 34 89 128 75 33 91 131 79 34 91 131 79 34 91 130 79 34 91 131 79 34 start (resurface 2) start (resurface 1) -100.0 -90.0 -80.0 -70.0 -60.0 -50.0 -40.0 -30.0 -20.0 -10.0 0.0 m ea n pe rc en t ch an ge f ro m ba se lin e p a s i sc or e study week w28 pasi 100 w28 pasi 90–99 lte start (resurface2) w28 pasi 75–89 w28 pasi 50–74 lte start (resurface1) number of patients: w28 pasi 100 w28 pasi 90–99 w28 pasi 75–89 w28 pasi 50–74 91 131 79 34 91 131 79 34 91 131 79 34 81 117 63 22 82 121 63 26 85 122 70 27 84 127 70 33 83 127 75 33 86 125 76 33 86 129 78 34 89 130 79 34 91 130 78 34 90 131 78 34 91 131 79 34 90 129 78 34 89 128 75 33 91 131 79 34 91 131 79 34 91 130 79 34 91 131 79 34 start (resurface 2) start (resurface 1) -100.0 -90.0 -80.0 -70.0 -60.0 -50.0 -40.0 -30.0 -20.0 -10.0 0.0 m ea n pe rc en t ch an ge f ro m ba se lin e p a s i sc or e study week w28 pasi 100 w28 pasi 90–99 lte start (resurface2) w28 pasi 75–89 w28 pasi 50–74 lte start (resurface1) number of patients: w28 pasi 100 w28 pasi 90–99 w28 pasi 75–89 w28 pasi 50–74 91 131 79 34 91 131 79 34 91 131 79 34 81 117 63 22 82 121 63 26 85 122 70 27 84 127 70 33 83 127 75 33 86 125 76 33 86 129 78 34 89 130 79 34 91 130 78 34 90 131 78 34 91 131 79 34 90 129 78 34 89 128 75 33 91 131 79 34 91 131 79 34 91 130 79 34 91 131 79 34 start (resurface 2) start (resurface 1) -100.0 -90.0 -80.0 -70.0 -60.0 -50.0 -40.0 -30.0 -20.0 -10.0 0.0 m ea n pe rc en t ch an ge f ro m ba se lin e p a s i sc or e study week w28 pasi 100 w28 pasi 90–99 lte start (resurface2) w28 pasi 75–89 w28 pasi 50–74 lte start (resurface1) number of patients: w28 pasi 100 w28 pasi 90–99 w28 pasi 75–89 w28 pasi 50–74 91 131 79 34 91 131 79 34 91 131 79 34 81 117 63 22 82 121 63 26 85 122 70 27 84 127 70 33 83 127 75 33 86 125 76 33 86 129 78 34 89 130 79 34 91 130 78 34 90 131 78 34 91 131 79 34 90 129 78 34 89 128 75 33 91 131 79 34 91 131 79 34 91 130 79 34 91 131 79 34 start (resurface 2) start (resurface 1) -100.0 -90.0 -80.0 -70.0 -60.0 -50.0 -40.0 -30.0 -20.0 -10.0 0.0 m ea n pe rc en t ch an ge f ro m ba se lin e p a s i sc or e study week w28 pasi 100 w28 pasi 90–99 lte start (resurface2) w28 pasi 75–89 w28 pasi 50–74 lte start (resurface1) number of patients: w28 pasi 100 w28 pasi 90–99 w28 pasi 75–89 w28 pasi 50–74 91 131 79 34 91 131 79 34 91 131 79 34 81 117 63 22 82 121 63 26 85 122 70 27 84 127 70 33 83 127 75 33 86 125 76 33 86 129 78 34 89 130 79 34 91 130 78 34 90 131 78 34 91 131 79 34 90 129 78 34 89 128 75 33 91 131 79 34 91 131 79 34 91 130 79 34 91 131 79 34 start (resurface 2) start (resurface 1) -100.0 -90.0 -80.0 -70.0 -60.0 -50.0 -40.0 -30.0 -20.0 -10.0 0.0 m ea n pe rc en t ch an ge f ro m b as el in e p a s i sc or e study week number of patients: w28 pasi 100 w28 pasi 90–99 w28 pasi 75–89 w28 pasi 50–74 91 131 79 34 91 131 79 34 91 131 79 34 81 117 63 22 82 121 63 26 85 122 70 27 84 127 70 33 83 127 75 33 86 125 76 33 86 129 78 34 89 130 79 34 91 130 78 34 90 131 78 34 91 131 79 34 90 129 78 34 89 128 75 33 91 131 79 34 91 131 79 34 91 130 79 34 91 131 79 34 early and maintained response levels in psoriasis patients treated with tildrakizumab kim a papp;1 jensen yeung;2 neil shear;3 lorne albrecht;4 charles lynde;5 jingchuan zhang;6 yang zhao;6 jeff parno;6 alan m mendelsohn;6 melinda gooderham7 1k. papp clinical research, and probity medical research, waterloo, on, ca; 2women’s college hospital and sunnybrook health sciences centre, university of toronto, toronto, on, ca; and probity medical research, waterloo, on, ca; 3division of dermatology, sunnybrook health sciences centre, university of toronto, toronto, on, ca; 4enverus medical, surrey, bc, canada; 5department of medicine, university of toronto, toronto, on, ca; 6sun pharmaceutical industries, inc., princeton, nj, usa; 7probity medical research, and skin centre for dermatology, peterborough, on, ca; and queen’s university, kingston, on, ca introduction • tildrakizumab is an igg1/κ monoclonal antibody that selectively inhibits the p19 subunit of interleukin-23 and is approved in the us, europe, and australia to treat adult patients with moderate to severe plaque psoriasis1 • the efficacy and safety of tildrakizumab has been demonstrated in two phase 3, double-blind, randomized, controlled trials (resurface 1, nct01722331; and resurface 2, nct01729754)2,3 • this post hoc analysis examined the long-term efficacy of tildrakizumab 100 mg up to week 148 among patients achieving various psoriasis area and severity index (pasi) responses at week 28 in resurface 1 and 2 methods • both resurface 1 and resurface 2 used a three-part design:3 — part 1 (0–12 weeks): patients were randomized (1:2:2) to blinded subcutaneous placebo or tildrakizumab 100 or 200 mg at weeks 0 and 4 — part 2 (12–28 weeks): patients previously receiving placebo were rerandomized to tildrakizumab 100 or 200 mg at weeks 12 and 16 and every 12 weeks (q12w) thereafter. patients continuing tildrakizumab from part 1 received a placebo injection at week 12 to maintain the blind and a dose of tildrakizumab at weeks 16 and 28. at week 28, tildrakizumab nonresponders (pasi <50) discontinued — part 3 (resurface 1: 28–64 weeks; resurface 2: 28–52 weeks): tildrakizumab responders (pasi ≥75) were rerandomized to receive placebo every 2 weeks (resurface 1) or tildrakizumab 100 or 200 mg q12w (resurface 1 and 2). responders who were rerandomized to placebo were retreated with the same tildrakizumab dose upon relapse (defined as reduction in maximum pasi response by 50%) • patients who received tildrakizumab in part 1 and achieved pasi ≥50 at the end of part 3 were eligible to enter the long-term extension (lte) study3 • patients treated with tildrakizumab 100 mg in parts 1–3 (at weeks 0, 4, and every 12 weeks after) and who received ≥1 dose during the lte were included in this analysis • percent pasi improvement from baseline to week 148 was examined for patients achieving pasi 50–74, 75– 89, 90–99, and 100 responses at week 28 using both observed data and imputed data with last observation carried forward (locf) results • a total of 335 patients were included in the analysis table. baseline demographics and clinical characteristics by % pasi improvement from baseline to week 28 pasi 50–74 (n = 34) pasi 75–89 (n = 79) pasi 90–99 (n = 131) pasi 100 (n = 91) age, years 46.9 (14.36) 45.9 (12.78) 45.2 (13.06) 42.4 (14.07) male, n (%) 26 (76.5) 53 (67.1) 94 (71.8) 62 (68.1) body surface area, % 34.5 (20.11) 31.1 (16.43) 33.7 (18.79) 29.0 (16.06) disease duration, years 13.9 (10.44) 18.0 (12.42) 16.9 (11.18) 14.5 (10.83) pasi score 20.24 (8.80) 19.46 (6.44) 20.99 (8.03) 18.49 (5.82) comorbidities, n (%) psa 7 (20.6) 11 (13.9) 22 (16.8) 16 (17.6) diabetes 4 (11.8) 7 (8.9) 9 (6.9) 8 (8.8) cvd 9 (26.5) 21 (26.6) 25 (19.1) 22 (24.2) prior biologics, n (%) 4 (11.8) 10 (12.7) 2 (19.8) 11 (12.1) data are mean (standard deviation) unless otherwise specified. cvd, cardiovascular disease; pasi, psoriasis area and severity index; psa, psoriatic arthritis. • patients had longstanding psoriasis (mean 16.1 years), but 85.2% had not previously been treated with a biologic (table) • mean pasi improvements at week 4 were 27.1%, 36.6%, 44.7%, and 52.5% for week 28 pasi 50–74, 75–89, 90–99, and 100 groups, respectively • a greater mean pasi response at week 8 was indicative of a greater mean pasi response at week 28 (figure) • responses were sustained through week 148 in patients achieving a week 28 mean pasi 75 response or higher — responses were 85.3%, 92.4%, and 95.4% for pasi 50–74, 75–89, 90–99, and 100, respectively • patients achieving week 28 pasi 50–74 had continuous mean pasi improvement from week 28 (64.4%) to week 52 (79.4%) and week 64 (82.2%); responses were further sustained through 148 weeks (81.4%) • results were similar when using either data as observed or imputed using locf presented at fall clinical dermatology conference for pas & nps 2020, april 3–5, orlando, fl, usa discussion • patients who received tildrakizumab and achieved pasi ≥90 at week 28 had rapid improvements as early as week 4 • among patients achieving pasi ≥50 at week 28, pasi improvements were improved or sustained through 148 weeks references 1. frampton je. am j clin dermatol. 2019;20(2):295–306. 2. reich k, papp ka, blauvelt a, et al. lancet. 2017;390(10091):276–88. 3. reich k, warren rb, iversen l, et al. br j dermatol. 2020;182(3):605–17. acknowledgments writing and editorial support was provided by asclepius analytics, llc; and kathleen pieper, phd, of alphabiocom, llc; and was funded by sun pharmaceutical industries, inc. disclosures kap has served as consultant and/or investigator and/or speaker for abbvie, akros, allergan, amgen, anacor, arcutis, astellas, astrazeneca, baxalta, baxter, boehringer ingelheim, bristol-myers squibb, canfite, celgene, coherus, dermira, dow pharma, eli lilly, forward pharma, galderma, genentech, gilead sciences, glaxosmithkline, inflarx gmbh, janssen, kyowa hakko kirin, leo pharma, medimmune, meiji seika pharma, merck sharp & dohme, merck-serono, mitsubishi pharma, moberg pharma, novartis, pfizer, prcl research, regeneron, roche, sanofiaventis/genzyme, takeda, ucb, and valeant/bausch health; on a steering committee and/or advisory board for abbvie, amgen, astellas, baxter, boehringer ingelheim, bristol-myers squibb, celgene, dow pharma, eli lilly, galderma, janssen, kyowa hakko kirin, merck sharp & dohme, merck-serono, novartis, pfizer, regeneron, sanofi-aventis/genzyme, ucb, and valeant/bausch health; and as scientific officer for akros, anacor, and kyowa hakko kirin. la has served as an advisor/ consultant for, has received grants/honoraria from, and has served as a speaker for abbvie, celgene, ds biopharma, eli lilly, galderma, janssen, leo pharma, novartis, regeneron, sanofi genzyme, and valeant. jy has been a speaker, consultant, and investigator for abbvie, allergan, amgen, astellas, boehringer ingelheim, celgene, centocor, coherus, dermira, eli lilly, forward, galderma, glaxosmithkline, janssen, leo pharma, medimmune, merck, novartis, pfizer, regeneron, roche, sanofi genzyme, takeda, ucb, valeant, and xenon. ns has been a paid consultant for abbvie; actelion; biogen; celgene; eli lilly; janssen; leo pharma; novartis; sanofi; and sun pharmaceutical industries, inc. cl has received funding from abbvie, amgen, boehringer ingelheim, celgene, coherus, dermira, eli lilly, galderma, innovaderm, janssen, leo pharma, merck, merck sharp & dohme , medimmune, novartis, pfizer, regeneron, and xoma; and reimbursement of travel, accommodation, and hospitality expenses from abbvie, amgen, boehringer ingelheim, celgene, eli lilly, janssen, leo pharma, merck, merck sharp & dohme, novartis, pfizer, and valeant. jz and yz were employees of sun pharmaceutical industries, inc., at the time of study conduct. jp has served as statistical consultant for sun pharmaceutical industries, inc.; and kyowa kirin pharmaceutical development, inc. amm is an employee of sun pharmaceutical industries, inc. mg has been an investigator, consultant, and/or speaker for abbvie; actelion; akros; amgen; arcutis; boehringer ingelheim; bristolmyers squibb; celgene; dermira; eli lilly; galderma; glenmark; glaxosmithkline; janssen; leo pharma; medimmune; merck; novartis; pfizer; regeneron; roche; sanofi genzyme; sun pharmaceutical industries, inc.; ucb; and valeant; and has been on an advisory board for abbvie; amgen; boehringer ingelheim; celgene; eli lilly; galderma; janssen; leo pharma; novartis; pfizer; regeneron; sanofi genzyme; sun pharmaceutical industries, inc.; and valeant. clinical efficacy and tolerability of a cosmetic growth factor serum for overall facial photodamage elizabeth t. makino, bs ccra mba; priscilla tan, ba; rahul c. mehta, phd research & development skinmedica, an allergan company, irvine, ca, usa presented at the fall clinical dermatology conference series, october 12-15, 2017, las vegas, nv, usa background photodamaged skin is characterized by the presence of fine/coarse lines, mottled pigmentation, among other changes to facial skin. growth factors (gf) have been shown to affect different pathways of skin repair and rejuvenation. objective to assess and compare the efficacy and tolerability of different facial treatments designed to improve photodamaged facial skin. results results herein focus on the comparison between the tns essential serum and placebo treatment groups: ● thirty-five subjects (tns es: n=19, placebo: n=16), aged 44-69 years with fst i-v who identified as caucasian (74%), asian (17%) and african american (9%) completed the study. o subjects in the tns es and placebo treatment groups presented with mean scores of 5.55 and 5.72, respectively, for overall photodamage. o three subjects in the placebo group voluntarily withdrew from the study, not due to adverse events (ae), and none for tns es group. ● twice-daily use of tns es showed early improvements at week 2 and significant long-term improvements at weeks 4, 8, and 12 compared to baseline in all parameters except for skin tone evenness at weeks 2 and 4. (figure 1; all p≤0.031; wilcoxon signedrank test; week 2: n=19, week 4: n=17, week 8: n=18, week 12: n=19). ● tns es was highly-rated by subjects for self-perceived efficacy with a statistically significant proportion of favorable responses observed for all parameters at week 12 (figure 2; all p≤0.004; binomial test; n=19). ● both treatments were well-tolerated with tolerability scores remaining similar to baseline scores. 6 aes for the tns es group and 4 aes for the placebo group were reported as unlikely to be related to treatment and resolved by the end of the study. conclusions results from this study demonstrate that tns essential serum, a cosmeceutical product containing a high concentration of physiologically balanced growth factors reversed signs and symptoms of skin aging significantly more than cleanser, moisturizer, and sunscreen alone. the addition of tns essential serum to a basic skincare regimen helped improve global fine and coarse lines/wrinkles, facial photodamage, skin tone evenness and tactile roughness. study design • single-center, double-blind, randomized, placebo-controlled clinical usage study • twelve week study duration with visits at baseline, weeks 2, 4, 8 and 12. inclusion criteria • male and female subjects in good general health aged 35-70 years with moderate to severe overall facial photodamage with fitzpatrick skin type (fst) i-vi • subjects were required to have a baseline score of 6 to 9 for the overall photodamage scale. subjects were willing to not apply any other topical products (skin lightening, retinoids, alpha/beta/poly-hydroxy acids), undergo facial treatments nor begin new cosmetic facial make-up throughout the duration of the study. study treatments four treatment groups: tns essential serum (tns es; active gf serum) serum a (active cosmetic test formula) serum b (active cosmetic test formula) placebo (basic skincare regimen) all subjects were provided the placebo regimen, consisting of facial cleanser, moisturizer, and spf 30 physical sunscreen, to use during the study. subjects were randomized to one of the treatment groups. all 3 active treatment groups used their serum twice-daily (once in the morning and night, after cleansing). facial cleanser and moisturizer were used twice-daily and sunscreen was used once in the morning (and as needed throughout the day). clinical assessments investigator gradings were performed at all visits using a modified griffiths’ 10point grading scale, where 0=none (best possible condition), 1-3=mild, 46=moderate, and 7-9=severe (worst condition possible), with half-points allowed as necessary to differentiate degrees of severity for the following efficacy parameters: • overall photodamage • fine lines/wrinkles (periocular, perioral, forehead and cheeks) • coarse lines/wrinkles (periocular, perioral, forehead and cheeks) • skin tone evenness (red/brown blotchiness) • tactile roughness tolerability assessments for erythema and scaling, using a 4-point scale (0=none, 1=mild, 2=moderate, 3=severe) were conducted at all visits. subjective parameters, including burning/stinging, itching, tightness, and tingling were assessed by the subjects. subject self-assessment questionnaires at all follow-up visits, subjects completed a questionnaire regarding selfperceived efficacy, product texture and product attributes. standardized digital photography standardized digital photographs were taken at all visits using the visia-cr photo system (canfield imaging systems, fairfield, new jersey). disclosures this study was sponsored by allergan. all authors met the icmje authorship criteria. all authors are employees of allergan. week 12 figure 3: early improvements at week 2 (female, age 62, fst ii, tns es group) week 2 figure 1: investigator efficacy assessments baseline baseline week 12 figure 2: subject questionnaire at week 12 figure 4: long-term improvements at week 12 (male, age 62, fst iii, tns es group) figure 5: long-term improvements at week 12 (female, age 69, fst ii, tns es group) 0% 20% 40% 60% 80% 100% made my skin look dewy and fresh reduced the appearance of lines/wrinkles on my forehead reduced the appearance of lines/wrinkles around my mouth (upper lip, smile lines) made my skin look firmer and more youthful made my lines/wrinkles look less apparent reduced the appearance of lines/wrinkles around my eyes improved the texture of my skin made my skin look more lifted and firm made my skin look radiant through-out the day made my skin feel smooth and soft made my skin feel hydrated “the test products…” tns essential serum placebo baseline 75 80 85 90 95 100 0 2 4 8 12 pe rc en t o f b as el in e o ve ra ll ph ot od am ag e time (weeks) overall photodamage tns essential serum placebo 75 80 85 90 95 100 0 2 4 8 12 pe rc en t o f b as el in e g lo ba l f in e li ne s/ w ri nk le s time (weeks) global fine lines/wrinkles 75 80 85 90 95 100 0 2 4 8 12p er ce nt o f b as el in e of g lo ba l c oa rs e li ne s/ w ri nk le s time (weeks) global coarse lines/wrinkles 75 80 85 90 95 100 0 2 4 8 12 pe rc en t o f b as el in e of s ki n to ne ev en ne ss time (weeks) skin tone evenness 75 80 85 90 95 100 0 2 4 8 12 pe rc en t o f b as el in e of t ac til e ro ug hn es s time (weeks) tactile roughness * * * * * * * * *significant improvements versus placebo (all p≤0.04 treatment comparisons; wilcoxon ranked-sum test) fc17posterallergangrowthserum.pdf clinical efficacy and tolerability of a topical hq-free serum on females with self-reported pregnancy-induced facial melasma elizabeth t. makino, bs ccra mba; priscilla tan, ba; rahul c. mehta, phd research & development skinmedica, an allergan company, irvine, ca, usa presented at the fall clinical dermatology conference series, october 12-15, 2017, las vegas, nv, usa background melasma, a progressive form of hyperpigmentation, occurs more often in healthy women than men. the actual etiology is indefinite; however, pregnancy, hormonal changes, uv/sun exposure, photosensitizing medications, and genetic predisposition have all been considered as contributing factors. this dysfunction of the pigmentary system results in symmetric brown or gray-brown patches on sun-exposed areas of the face, particularly on the forehead, cheeks, upper lip, and chin. often the psychosocial impact of melasma leads to a negative effect on quality of life and emotional well-being. objective to assess the cosmetic efficacy and tolerability of a hq-free and retinol-free serum (lyt2), in non-pregnant women with mild to severe melasma which was self-perceived as being induced by a previous pregnancy. results • the hq-free and retinol-free serum demonstrated a statistically significant decrease in clinical grading scores at weeks 4, 8 and 12 when compared with baseline for the following parameters (all p<0.001; wilcoxon signed-rank test): − overall hyperpigmentation − melasma area and severity index (masi) • statistically significant increase in mean scores for global improvement in overall hyperpigmentation at all visits (all p<0.001; wilcoxon signed-rank test) • melasqol combined score showed a statistically significant improvement at week 12 compared to baseline indicating an increased perception of quality of life (p<0.03; wilcoxon signed-rank test). • corneometer and tewameter measurements continuously improved from baseline at all follow-up visits, indicating an improvement in skin hydration and skin barrier function, respectively. • image analysis for brightness (l*) showed statistically significant improvements from baseline at all follow-up visits (all p≤0.025; paired t-test). • lyt2 was well-tolerated with tolerability scores remaining similar to baseline scores. • highly rated by subjects for self-perceived efficacy and product texture/attributes with a significant proportion of subjects agreeing to favorable responses by week 12. − 97% of subjects were satisfied with lyt2 by week 12 − 77% of subjects saw moderate or marked improvement by week 12 − 83% of subjects agreed it performed better than past facial treatments conclusions results from this study support the efficacy and tolerability of this hq-free and retinol-free serum in improving the appearance of mild to severe facial melasma in subjects with self-perceived pregnancy-induced melasma. study design • twelve-week, single-center clinical usage study with visits at baseline, weeks 4, 8 and 12. subject demographics • thirty female subjects aged 30-50 years with fitzpatrick skin types (fst) ii to iv presenting with mild to severe overall hyperpigmentation on the face due to melasma which is self-perceived to be induced by a previous pregnancy completed the study. • caucasian (73%), asian (20%) and african american (7%) treatment all subjects received lyt2, cleanser, moisturizer and sunscreen. subjects applied lyt2 twice-daily after cleansing. all subjects used cleanser and moisturizer twicedaily, and a physical sunscreen once in the morning (and as needed throughout the day). clinical assessments at all visits, the investigator assessed for: • overall hyperpigmentation (0-9 scale; 0=none, 1-3=mild, 4-6=moderate, 79=severe) • global improvement in overall hyperpigmentation (0-5 scale) • melasma area and severity index (masi) − each subject’s face was divided into 4 areas to be evaluated separately: forehead (f), right malar region (mr), left malar region (ml), and chin (c). − for each area, the pigment intensity (pi), lesion size (a) and homogeneity (h) was assessed. − masi score for the whole face was calculated using the following equation: masi = 0.3 (pif + hf) af + 0.3 (pimr + hmr) amr + 0.3 (piml+ hml) aml + 0.1 (pic + hc) ac − the values 0.3, 0.3, 0.3, and 0.1 represent the respective percentages of total facial area. the maximum score for masi is 48 and the minimum score is 0. tolerability assessments for erythema, scaling, edema, burning, stinging, and itching were graded on a 4-point scale at all visits. subject self-assessment questionnaires at all follow-up visits, subjects completed a self-assessment questionnaire on selfperceived efficacy, product texture and product attributes. at baseline and week 12, subjects completed a melasma quality of life (melasqol) questionnaire (likert scale: 1=not bothered at all to 7=bothered all the time). standardized digital photography standardized digital photographs were taken using the visia-cr imaging system (canfield imaging systems) at all visits. image analysis on a target dark spot for skin brightness (l*) was conducted for each time point. bioinstrumentation corneometer and tewameter measurements were conducted for all visits. disclosures this study was sponsored by allergan. all authors met the icmje authorship criteria. all authors are employees of allergan. figure 5: 44 y/o caucasian (fst iv) at baseline (left) and after 12 weeks of treatment (right) figure 2: 41 y/o caucasian (fst iv) at baseline (left) and after 12 weeks of treatment (right) figure 4: melasma quality of life (melasqol) subject questionnaire figure 3: overall hyperpigmentation figure 1: melasma area and severity index (masi) 3.8 4 4.2 4.4 4.6 4.8 5 0 4 8 12 m ea n s co re s time (weeks) * * * 7 8 9 10 11 12 13 0 4 8 12 m ea n s co re s time (weeks) *statistically significant improvements vs. baseline (all p<0.001; wilcoxon signed-rank test). * * * *statistically significant improvements vs. baseline (all p<0.001; wilcoxon signed-rank test). 1 2 3 4 5 6 7 the appearance of your skin condition frustration about your skin condition embarrassment about your skin condition feeling depressed about your skin condition the effects of your skin condition on your interactions with other people (e.g. interactions with family, friends, close relationship, etc.) the effects of your skin condition on your desire to be with people your skin condition making it hard to show affection skin discoloration making you feel unattractive to others skin discoloration making you feel less vital or productive skin discoloration affecting your sense of freedom baseline week 12* * * *statistically significant improvements vs. baseline (all p≤0.049; wilcoxon signed-rank test). fc17posterallerganmelasma.pdf powerpoint presentation poster #18223 long-term proactive management of psoriasis vulgaris with fixed-dose combination of calcipotriene 0.005% and betamethasone dipropionate 0.064% foam: results of a phase iii randomized controlled trial mark lebwohl1, jean-philippe lacour2, monika liljedahl3, charles lynde4,5, marie holst mørch3, diamant thaçi6 and richard b warren7 1department of dermatology, icahn school of medicine at mount sinai, new york, ny, usa; 2department of dermatology, university hospital of nice, nice, france; 3leo pharma a/s, ballerup, denmark; 4lynde dermatology, probity medical research, markham, on, canada; 5department of medicine, university of toronto, toronto, on, canada; 6institute and comprehensive center for inflammation medicine, university of lübeck, lübeck, germany; 7dermatology centre, salford royal nhs foundation trust and nihr biomedical research centre, university of manchester, manchester, uk materials and methods introduction presented at aad annual meeting 2020, denver, colorado, usa, march 20–24, 2020  eligible patients for this phase iii, multicentre trial received once-daily cal/bd foam during the 4-week open-label lead-in phase (figure 1). ─ patients with trunk and/or limb psoriasis, involving 2–30% of body surface area (bsa); physician’s global assessment (pga) of disease severity ≥’mild’; modified psoriasis area and severity index (m-pasi) ≥2.  patients achieving success at the end of the open-label lead-in phase (pga score ‘clear’/‘almost clear’ [pga <2] with ≥2-grade improvement from baseline of the open-label lead-in phase) were randomized 1:1 to twice-weekly cal/bd foam or vehicle foam for 52 weeks (figure 1). primary objective and endpoints  to evaluate the efficacy of a twice-weekly proactive maintenance regimen with cal/bd foam compared with reactive management with vehicle foam in the prevention of relapse in patients with psoriasis. ─ time to first relapse (defined as a pga score of at least ‘mild’ [pga≥2]). time to first relapse remission  patients in the proactive group had 41 extra days in remission compared to patients in the reactive group (p<0.001), over 1 year (95% ci, 29–53 days). results patient population  545 patients were randomized (safety analysis set [sas]); 521 achieved treatment success in the open-label lead-in phase (proactive n=256; reactive n=265 [full analysis set (fas)]). 251 (46.1%) patients completed the trial.  disease characteristics at randomization were similar between groups. mean age of randomized patients was 52.2 years; 91% of patients were white and 68% male.  82% of randomized patients in each treatment group had a pga score of ‘moderate’ at baseline of the open-label lead-in phase. conclusions  proactive management with cal/bd foam was superior in prolonging time to first relapse, reducing number of relapses and increasing days in remission versus vehicle-controlled reactive management.  the results of this trial are promising. they are the first to demonstrate that proactive management with fixed-dose cal/bd foam could offer improved long-term control of psoriasis over conventional reactive treatment. secondary objective and endpoints  to evaluate the long-term efficacy (up to 52 weeks) of proactive management twice weekly as maintenance therapy compared with reactive management in patients with psoriasis. ─ number of relapses. ─ proportion of days in remission (pga<2). safety objective  safety objectives, endpoints and data are presented in poster #12797. rate of relapse  rate of relapse over 1 year was reduced by 46% in the proactive group compared to the reactive group (95% ci, 37–54%; p<0.001).  predicted number of relapses in 1 year was 4.0 in the proactive group and 7.5 in the reactive group. safety results  proactive management was well tolerated over the 52-week trial period (data presented in poster #12797). references 1. feldman, et al. am health drugs benefits. 2016:9;504‒513; 2. armstrong, et al. jama dermatol. 2013:149;1180‒1185; 3. bonnekoh, et al. emj dermatol. 2017:5;36‒43; 4. emc. enstilar summary of product characteristics 2018; 5. fda. enstilar prescribing information 2019; 6. paul, et al. j eur acad dermatol venereol. 2017:31;119‒126; 7. koo, et al. j dermatolog treat. 2016:27;120‒127 acknowledgements the authors thank the investigators and patients who participated in this trial. the authors would like to thank lauren whyte, phd, a freelance medical writer contracted by ashfield healthcare communications, part of udg healthcare plc, for medical writing support, funded by leo pharma in accordance with good publications practice (gpp3) guidelines (http://www.ismpp.org/gpp3). disclosures all authors met the icmje authorship criteria and had full access to the relevant data. neither honoraria nor payments were made for authorship. ml, j-pl, dt, rbw, cl have consulted for, conducted studies funded by, or received honoraria for services provided to leo pharma; ml, mhm are employees of leo pharma. fixed-dose combination calcipotriene (cal) 0.005%/betamethasone dipropionate (bd) 0.064% aerosol foam is approved for the treatment of psoriasis vulgaris (plaque psoriasis) for up to 4 weeks in adults (under the trade name enstilar® in the us and enstilar® or enstilum® in the eu). cal/bd foam is also approved in the us for adolescents 12–18 years. funding this study was funded by leo pharma.  topical therapies are considered first-line treatment for psoriasis,1 however maintaining long-term disease control is a challenge, with many patients untreated or undertreated.2 current topical psoriasis treatment relies on a reactive approach to disease flares, as opposed to a more long-term proactive approach.3  data supporting the efficacy and safety of calcipotriene 0.005% and betamethasone dipropionate 0.064% (cal/bd) foam approved as a reactive treatment are available from trials of 4and 12-weeks duration in patients with psoriasis vulgaris (plaque psoriasis).4,5,6,7  here, we report the efficacy of cal/bd foam in long-term proactive management of psoriasis over 52 weeks (nct02899962). data from the open-label lead-in phase of this trial are presented in poster #16830. table 1. time to first relapse *number of days from randomization until 50% of patients had experienced their first relapse. double-blind treatment during the maintenance phase  ‘proactive’ management was treatment with cal/bd foam twice-weekly for 52 weeks when in remission.  ‘reactive’ management was treatment with vehicle foam twice-weekly for 52 weeks when in remission.  relapse: pga≥2 [either previously treated and/or new skin area]). flare medication (as separate flare bottles) was cal/bd foam once-daily for 4 weeks for both the proactive and reactive management groups (figure 1). figure 2. patient disposition entered open-label lead-in phase (n=650) discontinued (n=105) • adverse event (n=2); lost to follow-up (n=9); w ithdrawal by patient (n=11); lack of efficacy (n=4); patient did not achieve treatment success at end of open-label lead-in phase (n=68); failed screening (n=1); other (n=10) proactive management (n=272 sas [n=256 fas]) reactive management (n=273 sas [n=265 fas]) completed the trial (n=251 sas [n=246 fas]) discontinued (n=141 sas) • adverse event (n=2); lost to follow-up (n=12); w ithdrawal by patient (n=30); lack of efficacy (n=20); patient did not achieve treatment success after open-label lead-in phase (n=3); other (n=9); patient not clear or almost clear (pga<2) after treatment of relapse (n=65). discontinued (n=153 sas) • adverse event (n=1); death (n=1); lost to follow-up (n=14); w ithdrawal by patient (n=36); lack of efficacy (n=16); patient did not achieve treatment success after open-label lead-in phase (n=2); other (n=13); patient not clear or almost clear (pga<2) after treatment of relapse (n=70). experienced at least one relapse (n=210 fas) experienced at least one relapse (n=237 fas) randomized into maintenance phase (n=545 sas [n=521 fas]) randomized in error* (n=24 [16 proactive and 8 reactive]) completed (n=5) discontinued (n=19) *excluded from fas the sas included all patients exposed to cal/bd foam or vehicle foam following randomization. the fas included all randomized patients who had treatment success at randomization.  43% reduction in risk of experiencing a first relapse for patients in the proactive group compared to reactive group (hazard ratio, 0.57; 95% confidence interval [ci], 0.47–0.69; p<0.001). figure 3. time to first relapse proactive (n=256) reactive (n=265) median time to first relapse* 56 days 30 days trial design and treatments figure 1. trial design screening & washout (up to 4 weeks) maintenance phase followup for 8 weeks 1 0 2 4 3 8 4 12 5 16 6 20 7 24 8 28 9 32 10 36 11 40 12 44 13 48 14 52 15 56 fu1 58 fu2 60 fu3 64visit week cal/bd foam once daily for 4 weeks* relapse (pga ≥2) 1:1 randomizationbaseline end of maintenance phase followup for rebound adults with plaque psoriasis * success following 4 weeks of once daily flare medication was defined as pga<2 (‘clear [0]’ or ‘almost clear’ [1]) ** patients re-started the twice-weekly maintenance according to the original randomization scheme. pga<2** pga ≥2 withdrawn openlabel lead-in phase cal/bd foam daily for 4 weeks proactive management: cal/bd foam twice weekly for 52 weeks reactive management: vehicle foam twice weekly for 52 weeks 1.0 0.8 0.6 0.4 0.2 0.0 1 28 56 84 112 140 168 196 224 252 280 308 336 364 days after randomizationp ro ba bi lit y of h av in g no t h ad re la ps e ye t number of patients with no relapse yet proactive reactive 256 265 219 198 128 73 100 40 83 32 75 25 65 17 47 15 41 11 36 8 34 8 31 7 31 6 24 5 patients who did not achieve pga<2 after 4 weeks of once-daily flare medication following relapse were withdrawn from the trial. treatment group proactive reactive slide number 1 skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 221 in-depth reviews a systematic review and meta-analysis of gene expression profiling for primary cutaneous melanoma prognosis graham h. litchman, do, ms1, giselle prado, md1, rebeca w. teplitz, do2, darrell s. rigel, md, ms3 1national society for cutaneous medicine, new york, ny 2new york institute of technology, college of osteopathic medicine, old westbury, ny 3ronald o. perelman department of dermatology, nyu grossman school of medicine, new york, ny melanoma has the highest mortality among all skin cancer types. there will be an estimated 96,000 new cases of melanoma diagnosed in 2019 and over 7,000 deaths.1 assessment of prognosis is critical in melanoma management. management plans may influence survival outcomes depending on whether less frequent intervention or more aggressive follow up is chosen. therefore, clinicians should be knowledgeable in issues critical to an accurate assessment of melanoma prognosis to achieve optimal patient management. gene expression profiling (gep) is one form of genomic testing that can be used immediately after diagnosis to prognosticate melanoma outcomes. gep samples rna and dna from a lesion to assess genetic characteristics, and the results can be used to guide further management. several gep tests have been described in the literature and some are commercially available. introduction to decrease morbidity and mortality from melanoma, it is imperative to identify patients who are at high risk for developing widespread disease. gene expression profiling (gep) technology may impact melanoma management as physicians are better equipped to measure prognosis. many different gep signatures have been investigated. we searched pubmed, cochrane central, and embase for studies on gep in primary melanoma prognosis and assessed gep signatures for prognostic and analytic validity and clinical impact. the relationship between gep and survival was measured using hazard ratios (hr) and odds ratios (or). we found twenty-nine articles comprising 9 gene signatures meeting inclusion criteria and conducted a meta-analysis on 6 studies on a 31-gene signature. high-risk gep status was associated with poorer recurrence-free survival (hr=7.22; 95% ci, 4.75-10.98), distant metastasis-free survival (hr=6.62; 95% ci, 4.91-8.91), and overall survival (hr=7.06; 95% ci, 4.44-11.22); as well as sentinel lymph node biopsy positivity (or=2.99; 95% ci, 2.15-4.15). with recent improvements in treating advanced melanoma, accurately assessing prognosis is important. this study has clinical implications for melanoma patients who may benefit from prognostic testing. these results may be useful to clinicians when ordering gep testing and help them make better management decisions. abstract skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 222 however, no studies have summarized the available evidence on gep for prognosis in melanoma. as this field is rapidly evolving, the purpose of this systematic review and meta-analysis was to consolidate the body of data on gep in melanoma prognosis. a total of 672 articles were identified through database searching. (figure 1) after the exclusion of duplicate references, 600 abstracts were screened, and 74 full-text articles and abstracts were retrieved. after then applying selection criteria, 29 articles were included in the systematic review. nine unique gene signatures were reported. (table 1) 243 gene in alonso et al., 34 archival melanoma samples with a mean follow-up time of 67 months were analyzed.2 they found 206 upregulated and 37 downregulated genes that were differentially expressed based on nodal status. the authors classified these genes based on the mechanism of action or biological function and decided to focus on genes related to epithelial-mesenchymal transition (emt). then 127 archival samples with a mean follow-up time of 117 months were analyzed to determine which emt genes were significantly associated with relapse-free survival (rfs). in univariate analysis, n-cadherin, osteonectin, and osteopontin expression were significantly associated with an increased incidence of metastases. however, when adjusted by breslow depth, these associations were no longer significant. in multivariate analysis, protein kinase c α (pkcα) expression was significantly associated with rfs. 254 gene winnepenninckx et al. was an early study to identify new prognostic markers using gep on cutaneous melanoma samples.3 it found 254 genes associated with prognosis. most of these genes were previously known to be correlated with thickness, but eight novel prognostic genes were identified. in a multivariate model adjusted for thickness, ulceration, age, and sex, the differential expression of 2 proteins were significantly associated with overall survival (os). leeds cohort sample conway et al. analyzed 156 primary melanomas in a training set and 198 melanomas in a validation set to determine prognostic markers.4 they found that increased expression of osteopontin was a significant predictor of shorter rfs in both unadjusted (hr=3.17; 95% ci, 1.91-5.26) and adjusted analyses (hr=3.33; 95% ci, 1.96-5.67). jewell et al.5 completed a follow-up study to conway et al.4 and identified a group of dna repair and associated genes that are overexpressed in patients with poor rfs. rad52 and top2a (both dna repair genes) were independent predictors of poor rfs. their observations support previous studies that suggest melanoma cells need to maintain genomic integrity in order to continue aggressive division. 2 or 4 subtype signature harbst et al.6 retrospectively analyzed a cohort of 223 primary melanomas for correlation with the 4 gene subclasses previously discovered by jonsson et al.7 using the 4-class signature, the melanomas were classified as high-immune (57), normallike (63), pigmentation (84), and proliferative (16). further analysis revealed 2 primary results systematic review skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 223 skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 224 table 1. gene signatures reported in the literature. gene signature author & year 243 differentially expressed genes alonso 20072 254 differentially expressed genes winnepenninckx 20063 leeds cohort sample conway 20094 jewell 20105 2 or 4 subtype harbst 20126 nsengimana 20158 2 subtype badal 20179 7 gene meyer 201210 9 gene brunner 201311 brunner 201812 31 gene analytic validity cook 201814 clinical management berger 201615 cook 201718 dengel 201716 farberg 201719 schuitevoerder 201817 svoboda 201820 prognostic validity gerami 201521 gerami 201522 cook 201723 ferris 201724 hsueh 201727 huang 201729 keller 201728 cook 201830 greenhaw 201826 keller 201831 zager 201825 53 gene sivendran 201413 forms of tumors: high-grade (proliferative/pigmentation) and low-grade (high-immune/normal-like). high-grade tumors were significantly more likely to have lower rfs (hr=4.94; 95% ci, 2.84-8.59) and lower overall survival (hr=3.66; 95% ci, 2.40-5.58). nsengimana et al.8 sought to independently replicate the gene signatures reported in harbst et al.6 on the leeds cohort sample4. the sample included 300 archival melanomas with differing prognosis (228 primaries, 76 metastases). using the 4-class signature, the melanomas were classified as high-immune (70), normal-like (75), pigmentation (76), proliferative (37), and unclassified (12). applying the 2-class signature, there were 135 high-grade lesions, 108 low-grade lesions, and 57 unclassified lesions. all molecular subtypes were correlated with ajcc stage, breslow depth, ulceration, and mitotic rate. mss analysis showed that even after adjusting for ajcc stage, molecular signature and presence of vascular invasion were independent prognostic factors. 2 subtype badal et al. analyzed 78 archival melanocytic tumors (27 nevi, 51 melanoma) with a mean os of 90 months.9 transcriptional profiling revealed 4,639 genes that were differentially expressed in nevi and melanoma. the authors found significantly increased expression of immuneand inflammatoryrelated genes and significant repression of endogenous viral elements in melanomas. they also discovered a distinct 122 gene epigenetic signature that varied between aggressive and better prognosis melanomas. the aggressive melanomas were enriched in genes involved in cell proliferation and repressed in genes involving oncogenic signaling pathways (e.g. tp53, tp63, tp73). the high-risk epigenetic gene signature was an independent prognostic indicator for os. 7 gene meyer et al. developed a 7 gene molecular profile predictive of high or low metastatic risk among stage i-ii patients using a training sample of 362 primary melanomas and validated on an independent cohort of 225 primary melanomas.10 the gene signature included 7 biomarkers: bax, bcl-x, pten, cox-2, loss of b-catenin, loss of mtap, and presence of cd20 positive b-lymphocytes. the high-risk gene signature was associated with shorter median os (88 months vs. not skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 225 reached; p<0.00001) and shorter median rfs (33 months vs. 88 months; p<0.001). 9 gene brunner et al. first published a retrospective cohort of archival melanomas (n=135) where gene signature was correlated with os.11 gene signature predicted os independently of ajcc staging (hr=3.83; p=0.0004). when combining ajcc staging and the 9 gene signature, patients in intermediate ajcc risk were reclassified into highor low-risk groups. in a more recent study, brunner et al. describe a retrospective cohort of thin melanomas (n=111) and melanomas with known sln status (n=203).12 high-risk 9gep had a sensitivity of 33% for thin melanomas. gep status and sln status were significant independent prognostic factors for rfs. 53 gene sivendran et al. developed a 53 gene panel that is predictive of rfs and dss in stage iiiii patients.13 the authors used a training sample of 40 primary melanomas and screened 446 genes until narrowing down to the 53 gene panel. in both univariate and multivariate analysis, the 53 gene signature correlated with both rfs and dss (p<0.001). the 53 gene panel was then validated on 48 primary melanomas. similar to the training set, cox univariate analysis found that the 53 gene signature correlated with rfs and mss. on multivariate analysis, it correlated with mss only. 31 gene the 31 gene signature test was the most widely studied in the literature. for clarity, studies related to the 31 gene signature are subdivided into analytic validity, clinical management, and prognostic validity. analytic validity cook et al. reported an inter-assay concordance of 99%, inter-instrument concordance of 95%, and inter-operator concordance of 100% for 31-gep.14 85% of specimens fulfilled minimum tumor content requirements, and technical success was 98%. clinical management berger et al. published a retrospective chart review that determined the impact of 31-gep results on clinical decisions including follow up frequency, imaging ordered, snlb, and referral to oncologists.15 156 patients were included (95 low-risk, and 61 high-risk). a change in management after 31-gep testing was seen in 53% of patients (37% of low-risk, 77% of high-risk). most of these management changes were concordant with the risk indicated by the test, i.e. high-risk patients resulted in increased intensity of management and vice versa. however, this study did not follow-up with patient outcomes. in a patient outcomes study, 63 stage 1b/iia melanoma cases who underwent 31-gep testing were analyzed for changes from surveillance to routine imaging frequency for 2 years.16 of the 13 high-risk patients, 12 were upgraded to routine imaging. a retrospective chart review showed that 31gep status was significantly associated with the clinical management of stage i and ii cm patients.17 stage 1/low-risk patients were more likely to be managed by dermatologists alone, while stage 2/high-risk patients were more likely to be followed by surgical oncology. a survey of 157 dermatologists who were presented 1 clinical scenario without gep information, but with a lowand high-risk result, found that respondents tended to choose a higher threshold breslow thickness skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 226 to order sentinel lymph node biopsy (slnb), imaging, or recommend referral if given a low-risk result.18 this corresponded with a lower threshold breslow thickness with a high-risk result. with the same study design as cook et al.19, a survey of 169 dermatology residents found that most respondents changed their recommendation for slnb, imaging, and referral in the risk appropriate direction after being given gep results.19,20 another survey of 181 dermatologists found that ulceration in thin lesions was the most important factor to impact a dermatologist’s decisions to order the 31-gep test.20 prognostic validity gerami et al. reported the initial validation study of 31-gep using a training set of 164 cases and a validation set of 104 cases with a minimum 5 year follow up.21 in multivariate analysis, a high-risk gep result was associated with a 9.5 times increased risk of developing any type of metastasis or locoregional recurrence. 31-gep status was an independent predictor of metastatic risk similar to ajcc stage, breslow depth, ulceration, and age. in a retrospective cohort of 217 patients who had undergone slnb and had a minimum 5year follow-up, 31-gep status was more predictive than slnb for all endpoints (rfs, dmfs, and os).22 an analysis of 782 primary cm found that 31gep status was a significant predictor of rfs, dmfs, os, and mss risk (p<0.05).23 31-gep class had a sensitivity of 76%, specificity of 67%, npv of 91%, and ppv of 39% for distant metastases occurrence. ferris et al. studied 205 patients with early stage cm and evaluated both 31-gep status and ajcc prediction.24 combining 31-gep results with ajcc predication accurately identified 90% of recurrences, 88% of distant metastases, and 82% of deaths. zager et al. studied 523 cm cases and found that 31-gep status was a significant independent predictor of rfs and dmfs in both univariate and multivariate analyses.25 an independent validation study of the 31gep test on 256 patients with stage i-ii melanoma found high sensitivity, specificity, and npv.26 mfs curves for this study and the gerami cohort21 were closely correlated. in a prospective cohort study of 322 realworld patients, hsueh et al. found that highrisk gep result was a stronger predictor of rfs than positive slnb (hr=7.15 vs. 2.46).27 however, the gep result was not a significant predictor of dmfs or os. keller et al. sought to determine whether 31gep status could be used to predict slnb positivity by enrolling 163 patients into a prospective cohort study.28 within the 15 high-risk 31-gep patients, only 3 patients had a positive slnb. 31-gep status was not a significant predictor of slnb positivity in stage 1 or 2. the authors concluded that 31gep status should not be a substitute for slnb in staging melanoma patients. in a retrospective cohort study of 128 melanomas, huang et al. found that high risk 31-gep was a better predictor of slnb positivity than breslow thickness, ulceration, and mitotic rate.29 this suggests that obtaining gep status prior to definitive surgical planning may be beneficial when slnb is not indicated by traditional pathologic variables. the combination of 31-gep class and nonsentinel lymph node status was able to skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 227 identify most patients (87%) who would experience distant metastases.30 the highest sensitivity for distant metastases was achieved by combining lymph node status and 31-gep results. keller et al. also evaluated the use of 31-gep in identifying patients with non-sentinel node (nsn) metastases. in a cohort of 287 patients, 39 had positive slnb.31 among the positive slnb patients, 8 also had positive nsn. 7/8 nsn positive patients had higher risk gep status. in chi-square analysis, gep status was a significant predictor of nsn metastases (p=0.0047). due to heterogeneity among reported gene signatures and paucity of reported studies for the different gep tests, the meta-analysis conducted was limited to data from the 31gene signature consisting of 6 studies on prognostic validity.24,26-30 (table 2) a funnel plot did not show evidence of publication bias. for 31-gene, the pooled hr for rfs was 7.22 (95% ci, 4.75-10.98). (figure 2a) however, there was significant heterogeneity seen between studies. the pooled hr for dmfs was 6.62 (95% ci, 4.91-8.91). (figure 2b) the pooled hr for os was 7.06 (95% ci, 4.44-11.22). (figure 2c) pooled ors were calculated for recurrence, distant metastases development, overall survival, and snlb positivity. the pooled or for recurrence was 9.42 (95% ci, 5.8415.20). (figure 3a) there was also significant heterogeneity seen between studies for this outcome. the pooled or for distant metastases was 7.93 (95% ci, 4.98-12.64). (figure 3b) the pooled or for overall survival was 6.43 (95% ci, 3.90-10.61). (figure 3c) the pooled or for slnb positivity was 2.99 (95% ci, 2.15-4.15). (figure 3d) table 2. studies included in meta-analysis. author & year sample size age in median years (range) stage median followup in years (range) gerami 201522 217 61 (2394) i:46 ii:112 iii:58 iv:1 not reporte d ferris 201724 205 61 (1889) i: 109 ii: 96 6.9 (0.115.4) hsueh 201727 322 58 (1887) none :3 i:209 ii:73 iii:36 iv:1 1.5 keller 201728 163 not reported t1:7 2 t2:9 1 not reported greenha w 201826 256 69 i:219 ii:24 23 months zager 201825 244 59 (1892) i:264 ii:93 iii:16 6 7.5 (5.016.5) commercially available gep tests are already impacting physician management decisions in real-world patients.17-22 through integrating this technology, physicians are now better positioned to counsel their melanoma patients regarding prognosis. with the recent improvements in treating advanced disease, accurately assessing prognosis is particularly important. a patient’s prognosis affects a clinician’s intensity of management. in the near future, clinicians may recommend immunotherapy for early stage high-risk patients. gep testing in this context could potentially play a significant discussion meta-analysis skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 228 figure 2. forest plot of hazard ratio and 95% ci for (a) recurrence free survival, (b) distant metastasis free survival, and (c) overall survival. skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 229 figure 3. forest plot of odds ratio and 95% ci for (a) recurrence, (b) distant metastasis, (c) overall survival, and (d) sentinel lymph node biopsy positivity. skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 230 role in honing risk predictions. adding gep testing in clinical trials as a stratifying characteristic may also better randomize patients with different baseline risks of metastasis. there are also several diagnostic challenges common to melanoma management that can be ameliorated by gep testing. for example, it can be difficult to determine whether a patient should undergo slnb for thin tumors, tumors with unknown thickness (shaved through the base), or older persons with lower rates of slnb positivity. a high-risk gep result may appropriately influence a clinician to refer a patient for this procedure. current nccn guidelines suggest that patients with a 5% risk of positive slnb should undergo slnb.32 although gep testing may help stratify patient risk for slnb positivity, gep is not currently recommended to replace slnb as evidenced by the results of this review. limitations were present in this systematic review and meta-analysis. most included studies were conducted retrospectively versus prospectively. although a comprehensive search strategy was employed, missing relevant studies may be unavoidable, especially those published in non-english language journals. some studies did not directly provide hrs with corresponding effect sizes requiring manual derivation from kaplan–meier survival curves. significant heterogeneity was noted when calculating the pooled hr for rfs and the pooled or for recurrence. also, several permutations of different melanoma gene profiles are being tested and developed. however, these new technologies are still early in their development and additional studies may impact on potential uses and adoption. in conclusion, the findings of this review have clinical implications for patients with melanoma to better assess their prognosis leading to more effective management of their disease. the results of this study may be useful when deciding to offer gep testing to primary cutaneous melanoma patients. search strategy this systematic review and meta-analysis followed the preferred reporting items for systematic reviews and meta-analyses (prisma) guidelines (prospero registration no. crd42018110114). electronic searches were performed in three databases for articles published from inception to september 24, 2018: pubmed medline, cochrane library central, and embase. search terms included: “gene expression profile,” “cutaneous melanoma,” “prognosis,” “risk,” “predict,” “31 gene,” “53 gene,” and “9 gene” (supplementary materials and methods). reference lists of all included studies and recent reviews were also assessed. ongoing clinical trials and unpublished studies were identified through clinicaltrials.gov. inclusion criteria all studies related to gene expression profiling or gene signatures in the prognosis of primary cutaneous melanoma patients. studies were required to measure prognostic validity, analytical validity, or clinical impact of gep. exclusion criteria case reports, review articles, articles with less than 10 samples, unpublished articles, and animal studies were excluded. use of gep in vitro, on non-human samples, and in silico reports were not included. all studies done on non-primary melanomas were methods skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 231 excluded. non-english studies were excluded. outcome measures the prognostic validity, analytical validity, and/or clinical impact of gep was determined. the relationship between gep and survival outcomes (recurrence-free survival (rfs), distant metastasis-free survival (dmfs), melanoma-specific survival (mss), or overall survival (os)) was measured using hazard ratios with confidence intervals, kaplan meier curves with survival estimates, cox univariate or multivariate analysis, or accuracy metrics for risk prediction. data extraction and quality appraisal all data were extracted from article text, tables, and figures. two reviewers (g.p. and r.t.) independently screened and reviewed each article for inclusion. each reviewer independently extracted data and discrepancies were resolved by discussion and consensus. if kaplan-meier graphs were provided without the hazard effect or 95% ci, these were estimated using previously described methods.33 risk of bias was assessed using the cochrane quips tool34 for assessing risk of bias in prognostic factor studies. (figure s1) statistical analysis all statistical analyses were performed using review manager, version 5.3 (cochrane collaboration, software update). the statistical heterogeneity between the included studies was assessed by the i2 statistic (i2 = 0–25%, no heterogeneity; i2 = 25–50%, moderate heterogeneity; i2 = 50– 75%, large heterogeneity; i2 = 75– 100%, extreme heterogeneity). a funnel plot was used to assess for publication bias. a random effects model was used to take into account the possible diversity and methodological variation among studies. summary statistics are presented as hazard ratios (hr) or odds ratios (or) as appropriate. all p values were 2-sided, and statistical significance was set at p < .05. conflict of interest disclosures: dr. darrell rigel is a consultant for castle biosciences. dr. graham litchman and dr. giselle prado are fellows of the national society for cutaneous medicine which receives grants from castle biosciences. funding: none corresponding author: graham h. litchman, do, ms 35 e 35th st. #208 new york, ny, 10016, usa phone: 203-940-0373 email: graham.litchman@gmail.com references: 1. siegel rl, miller kd, jemal a. cancer statistics, 2019. ca cancer j clin. 2019;69(1):7-34. nccn clinical practice guidelines in oncology. melanoma. version 3.2018. published july 12, 2018. 2. alonso sr, tracey l, ortiz p, et al. a highthroughput study in melanoma identifies epithelial-mesenchymal transition as a major determinant of metastasis. cancer res. 2007;67(7):3450-60. 3. winnepenninckx v, lazar v, michiels s, et al. gene expression profiling of primary cutaneous melanoma and clinical outcome. j natl cancer inst. 2006;98(7):472-82. 4. conway c, mitra a, jewell r, et al. gene expression profiling of paraffin-embedded primary melanoma using the dasl assay identifies increased osteopontin expression as predictive of reduced relapse-free survival. clin cancer res. 2009;15(22):6939-46. 5. jewell r, conway c, mitra a, et al. patterns of expression of dna repair genes and relapse from melanoma. clin cancer res. 2010;16(21):521121. 6. harbst k, staaf j, lauss m, et al. molecular profiling reveals lowand high-grade forms of primary melanoma. clin cancer res. 2012;18(15):4026-36. 7. jonsson g, busch c, knappskog s, geisler j, miletic h, ringner m, et al. gene expression profiling-based identification of molecular mailto:graham.litchman@gmail.com skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 232 subtypes in stage iv melanomas with different clinical outcome. clin cancer res 2010;16:3356– 67. 8. nsengimana j, laye j, filia a, et al. independent replication of a melanoma subtype gene signature and evaluation of its prognostic value and biological correlates in a population cohort. oncotarget. 2015;6(13):11683-93. 9. badal b, solovyov a, di cecilia s, et al. transcriptional dissection of melanoma identifies a high-risk subtype underlying tp53 family genes and epigenome deregulation. jci insight. 2017;2(9) 10. meyer s, fuchs tj, bosserhoff ak, et al. a seven-marker signature and clinical outcome in malignant melanoma: a large-scale tissuemicroarray study with two independent patient cohorts. plos one. 2012;7(6):e38222. 11. brunner g, reitz m, heinecke a, et al. a ninegene signature predicting clinical outcome in cutaneous melanoma. j cancer res clin oncol. 2013;139(2):249-58. 12. brunner g, gambichler t, reinhold u, et al. a prognostic gene expression profile complements staging of thin fatal melanomas and melanomas with known sentinel lymph node status. oncol res treat. 2018;41(s1):162. 13. sivendran s, chang r, pham l, et al. dissection of immune gene networks in primary melanoma tumors critical for antitumor surveillance of patients with stage ii-iii resectable disease. j invest dermatol. 2014;134(8):2202-2211. 14. cook rw, middlebrook b, wilkinson j, et al. analytic validity of decisiondx-melanoma, a gene expression profile test for determining metastatic risk in melanoma patients. diagn pathol. 2018;13(1):13. 15. berger ac, davidson rs, poitras jk, et al. clinical impact of a 31-gene expression profile test for cutaneous melanoma in 156 prospectively and consecutively tested patients. curr med res opin. 2016;32(9):1599-604. 16. dengel lt, hickman aw, slingluff cl. effect of gene expression profile (gep) testing on clinical management in 19% of consecutively treated patients with stage ib/iia melanoma at a single institution. j clin oncol. 2017; 35 (suppl; abstr e21080) 17. schuitevoerder d, heath m, cook rw, et al. impact of gene expression profiling on decisionmaking in clinically node negative melanoma patients after surgical staging. j drugs dermatol. 2018;17(2):196-199. 18. cook rw, glazer a, middlebrook b, et al. clinical impact of a 31‐gene expression profile test on guidance of sentinel lymph node biopsy, imaging and oncology referral. pigment cell melanoma res. 2017;30(1):92. 19. farberg as, glazer am, white r, rigel ds. impact of a 31-gene expression profiling test for cutaneous melanoma on dermatologists' clinical management decisions. j drugs dermatol. 2017;16(5):428-431. 20. svoboda rm, glazer am, farberg as, rigel ds. factors affecting dermatologists' use of a 31gene expression profiling test as an adjunct for predicting metastatic risk in cutaneous melanoma. j drugs dermatol. 2018;17(5):544547. 21. gerami p, cook rw, wilkinson j, et al. development of a prognostic genetic signature to predict the metastatic risk associated with cutaneous melanoma. clin cancer res. 2015;21(1):175-83. 22. gerami p, cook rw, russell mc, et al. gene expression profiling for molecular staging of cutaneous melanoma in patients undergoing sentinel lymph node biopsy. j am acad dermatol. 2015;72(5):780-5.e3. 23. cook rw, covington kr, monzon fa. continued evaluation of a 31-gene expression profile to predict metastasis in an expanded cohort of 782 cutaneous melanoma patients. pigment cell melanoma res. 2017;30:e73. 24. ferris lk, farberg as, middlebrook b, et al. identification of high-risk cutaneous melanoma tumors is improved when combining the online american joint committee on cancer individualized melanoma patient outcome prediction tool with a 31-gene expression profilebased classification. j am acad dermatol. 2017;76(5):818-825.e3. 25. zager js, gastman br, leachman s, et al. performance of a prognostic 31-gene expression profile in an independent cohort of 523 cutaneous melanoma patients. bmc cancer. 2018;18(1):130. 26. greenhaw bn, zitelli ja, brodland dg. estimation of prognosis in invasive cutaneous melanoma: an independent study of the accuracy of a gene expression profile test. dermatol surg. 2018; 27. hsueh ec, debloom jr, lee j, et al. interim analysis of survival in a prospective, multi-center registry cohort of cutaneous melanoma tested with a prognostic 31-gene expression profile test. j hematol oncol. 2017;10(1):152. 28. keller jk, schwartz t, lizalek jm, hsueh ec. utility of gene expression profiling in determining necessity of sentinel node biopsy in melanoma. ann surg oncol. 2017;24(s1):s148. skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 233 29. huang x, hewgley wp, guerrero w, fleming m. application of gene expression profiling in the management of cutaneous melanoma. ann surg oncol. 2017;24(s1):s144. 30. cook rw, covington kr, monzon fa. prognostic value of non-sentinel lymph node (non-sln) status and a prognostic 31-gene expression profile (gep) in stage iii cutaneous melanoma patients pigment cell melanoma res. 2018;31:e144. 31. keller j, schwartz t, lizalek j, hsueh e. exploring the role of gene expression profiling in the prediction of non-sentinel node status in cutaneous melanoma. ann surg oncol. 2018;24(s1):s67. 32. national comprehensive cancer network. nccn clinical practice guidelines in oncology: cutaneous melanoma. 2019. 33. tierney jf, stewart la, ghersi d, burdett s, sydes mr. practical methods for incorporating summary time-to-event data into meta-analysis. trials. 2007;8:16. doi:10.1186/1745-6215-8-16. 34. hayden ja, van der windt da, cartwright jl, côté p, bombardier c. assessing bias in studies of prognostic factors. ann intern med. 2013;158(4):280-6. skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 234 figure s1. risk of bias summary. supplemental materials & methods skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 235 pubmed #43 add search ((#1 or #2 or #8 or #10 or #11) and (#3) and (#6 or #7 or #9) not (#17 or #21 or #24 or #26 or #27 or #28 or #30 or #31 or #32 or #33 or #37))) filters: publication date from 2003/01/01 to 2018/09/24 422 09:51:40 #42 add search ((#1 or #2 or #8 or #10 or #11) and (#3) and (#6 or #7 or #9) not (#17 or #21 or #24 or #26 or #27 or #28 or #30 or #31 or #32 or #33 or #37))) 440 09:35:07 #41 add search (((#1 or #2 or #8 or #10 or #11) and (#3) and (#6 or #7 or #9) 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add search prognosis 1621781 09:11:57 #5 add search ((#1 or #2) and (#3)) 2595 09:11:28 #4 add search melanoma 121912 09:10:42 #3 add search cutaneous melanoma 121912 09:09:37 #2 add search gene expression profile 87564 09:08:19 #1 add search gene expression profiling 200024 09:07:52 skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 237 cochrane embase skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 585 brief articles cutaneous toxicities of pi3k inhibitors: a series of two cases and review of the literature simran a. chadha, bs1, jennifer l. shastry, md2, joel c. sunshine, md2, jennifer choi, md2*, lauren guggina, md2* 1northwestern university, feinberg school of medicine, chicago, il 2department of dermatology, feinberg school of medicine, northwestern university, chicago, il *these authors contributed equally phosphoinositide 3-kinase (pi3k) inhibitors are novel small molecule targeted inhibitors approved for the treatment of multiple hematologic malignancies, namely relapsed or refractory chronic lymphocytic leukemia (cll), follicular lymphoma (fl), small lymphocytic lymphoma (sll), and breast cancer.1,2 isoform-specific pi3k inhibitors are a subclass of this broader category, consisting of agents targeting the p110- isoform (alpelisib and taselisib), the p110- isoform (idelalisib), and the p110- and p110- isoforms (duvelisib).3 the specificity of these molecular targets allows for higher dosage while limiting toxicity; however, cutaneous, endocrine, and gastrointestinal toxicities are common. we report two photoaccentuated duvelisib-induced skin eruptions, both requiring interruption of therapy and resolving with systemic steroids. case 1 a 62-year-old man with a history of angioimmunoblastic t cell lymphoma (aitcl) presented with a pruritic skin eruption in the spring. the patient’s aitcl abstract phosphoinositide 3-kinase (pi3k) inhibitors are a class of antineoplastic agents currently approved for the treatment of multiple hematologic malignancies and breast cancer. these medications have specific molecular targets to limit toxicity; however, cutaneous adverse effects are frequently reported and can require cessation of therapy. morbilliform, eczematous, psoriasiform, and pityriasis rubra pilaris-like eruptions are most common, though exfoliative dermatitis and stevens-johnson syndrome/toxic epidermal necrolysis have also been reported. we highlight two cases of photoaccentuated skin reactions to duvelisib, a p110- and p110- isoform inhibitor. both cases required oral corticosteroids and interruption of therapy for definitive management due to severity. while one patient was able to tolerate re-challenge with duvelisib and continue on therapy, both patients experienced recurrence of cutaneous eruptions with repeat exposure, establishing a notable temporal correlation. thus, these cases contribute a novel presentation of adverse reactions to pi3k inhibitors to existing literature. introduction case presentation skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 586 figure 1. case 1 clinical image of the initial eruption reveals photo-accentuated erythematous scaly plaques on the face and neck (a). clinical image of the recurrent eruption demonstrates pink-orange scaly plaques on the face, neck, trunk, and extremities with sparing of the antecubital fossae (b). biopsies of the left forearm (c) and the left upper arm (d) show a chronic spongiotic dermatitis with scattered necrotic keratinocytes and a dermal infiltrate composed of lymphocytes and eosinophils (h&e, 100x, 200x). had been previously treated with chemotherapy and autologous stem cell transplant, initially achieving complete remission. recurrence of the aitcl prompted initiation of duvelisib three months prior to development of the skin eruption. on physical examination, the patient was noted to have erythematous, scaly thin plaques on the face, neck, dorsal hands and upper extremities with a psoriasiform appearance, accentuated in sun exposed areas. this photo-accentuated psoriasiform eruption improved after duvelisib was held for 1 month due to a transaminitis. one month after restarting the duvelisib, the patient presented with a new skin eruption. physical examination revealed confluent, scaly, erythematous plaques on the face, scalp, and trunk (figure 1a and 1b). there skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 587 figure 2. case 2 clinical images reveal erythematous papules coalescing into plaques on the neck, shoulders, and forearms with photo-accentuation (a, b). biopsy of the left arm (c) demonstrates a spongiotic epidermis with vesiculation, significant papillary dermal edema, and a perivascular and interstitial dermal infiltrate (h&e, 100x). higher power (d) reveals a perivascular and interstitial infiltrate composed of lymphocytes and eosinophils (h&e, 200x). were pink-orange scaly plaques on the bilateral palms with sharp demarcation at the wrists, well-demarcated pink plaques on the extremities, and areas of spared skin in flexural areas clinically resembling pityriasis interrupted due to the eruption; his skin improved with oral and topical steroids, and then worsened with subsequent rechallenge of duvelisib. multiple punch biopsies were performed throughout the evolution of the patient’s rash. histopathology demonstrated parakeratosis, skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 588 table 1. previously reported cutaneous toxicities of pi3k inhibitors age/ sex malignancy pi3k inhibitor time to reaction morphology histopathology reaction type treatment of cutaneous eruption pi3k therapy outcome successful rechallenge (if interrupted)? associated adverse events case 1 (our case) 62 m aitcl duvelisib 3 months photo-accentuated psoriasisform pink-orange scaly plaques on the face, neck, forearms, which generalized with areas of sparing parakeratosis, acanthosis, and spongiosis of epidermis, lymphocytic infiltrate with neutrophils and eosinophils in the upper dermis photoaccentuated prp-like systemic corticosteroids, topical corticosteroids interrupted no transaminitis case 2 (our case) 55 f ptcl duvelisib 1 month photo-accentuated erythematous papules coalescing into plaques on the face, neck, arms perivascular and interstitial dermatitis with eosinophils photoaccentuated morbilliform eruption systemic corticosteroids, topical corticosteroids, oral antihistamines interrupted yes transaminitis, neutropenia, fatigue gabriel et al. 65 m cll idelalisib 3 months exfoliative rash with diffuse scaling of torso, extremities, tongue, glans penis, and desquamation of soles not performed exfoliative dermatitis not specified not specified n/a transaminitis, normocytic anemia hammami et al. 56 m fl idelalisib 4 months skin eruption, unspecified subacute spongiotic dermatitis, superficial dermal lymphohistiocytic infiltrate with eosinophils eczematous systemic corticosteroids discontinued n/a colitis huilaja et al. 61 m cll idelalisib 1 months macular erythematous eruption with desquamation on upper arms/trunk, peeling on palms hyperkeratosis and focal parakeratosis, acanthotic thickening, focal spongiosis, perivascular lymphohistiocytic infiltrate with some eosinophils not specified oral corticosteroids, topical corticosteroids discontinued n/a transaminitis machan et al. 82 f fl idelalisib 11 months erythematosquamous papules and plaques on back/buttocks with pustules of scalp/forehead t-cell infiltration with psoriasiform epidermal hyperplasia, subcorneal pustule, and mild perivascular lymphocytic infiltrate psoriasiform topical corticosteroids interrupted yes none dewan et al. 59 m cll p110-delta inhibitor 17 months photodistributed erythematous papules and large plaques on arms/legs, which spread to face, scalp, trunk, soles psoriasiform epidermal hyperplasia, mild spongiosis, parakeratosis, intraepidermal/intracorneal neutrophils psoriasiform oral acitretin, topical corticosteroids, photoprotection interrupted yes not specified 57 m cll p110delta/gamma inhibitor 15 days guttate papules and erythematous plaques with overlying micaceous scale on knees and intertriginous areas, nail pitting, palmoplantar pustules psoriasiform dermatitis with inflamed parakeratosis psoriasiform topical corticosteroids, topical tacrolimus, topical retinoid interrupted yes not specified 81 m sll/cll p110-delta inhibitor 5 months thin erythematous papules coalescing into plaques with overlying micaceous scale on trunk/extremities spongiotic and suprabasilar acantholysis with superficial dermal lymphocytic infiltrate psoriasiform topical corticosteroids discontinued n/a not specified 72 m mzl p110-delta inhibitor 3 months thin erythematous plaques on gluteal cleft, inguinal folds; large plaques with overlying micaceous scale on neck, chest, extremities, scalp not performed psoriasiform topical corticosteroids discontinued (for colitis adverse effect) n/a colitis dewan et al. 40s f anaplastic oligodendroglioma dual panclass i pi3k inhibitor 4 days pruritic photodistributed orange-pink erythroderma with islands of sparing and overlying fine desquamative scale, palmoplantar keratoderma pityriasiform changes with alternating ortho and parakeratosis, spongiotic dermatitis, and numerous eosinophils prp-like systemic corticosteroids, oral acitretin, topical steroids, oral antihistamines not specified n/a essential tremor 60s m cll idelalisib 5 months diffuse orange-red erythroderma with islands of sparing, nonscarring alopecia, palmoplantar keratoderma pityriasiform changes with alternating ortho and parakeratosis, spongiotic dermatitis, and numerous eosinophils prp-like systemic corticosteroids, oral acitretin, topical corticosteroids, topical retinoids discontinued n/a leukopenia, anemia, thrombocyto penia, suppurative adenitis 60s m sll idelalisib 6 weeks diffuse orange-red patches with follicular prominence and islands of sparing over trunk/extremities subacute spongiotic dermatitis with pityriasiform scale and superficial perivascular lymphocytic infiltrate prp-ilke systemic corticosteroids, topical corticosteroids discontinued n/a peripheral eosinophilia, transaminitis abbreviations: pityriasis rubra pilaris (prp), angioimmunoblastic t cell lymphoma (aitcl), peripheral t cell lymphoma (ptcl), chronic lymphocytic leukemia (cll), follicular lymphoma (fl), small lymphocytic lymphoma (sll), marginal zone lymphoma (mzl). skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 589 acanthosis, and spongiosis of the epidermis and a lymphocytic infiltrate with occasional neutrophils and eosinophils in the upper dermis. occasional necrotic keratinocytes were seen (figure 1c and 1d). repeat imaging demonstrated no evidence of lymphoma; his aitcl was considered to be in remission on duvelisib. given worsening of the rash after multiple re-challenges, the patient was diagnosed with a photoaccentuated, duvelisib-induced prp-like skin eruption. case 2 a 55-year-old woman with a history of primary refractory cd30-positive peripheral t cell lymphoma (ptcl) presented with a pruritic eruption on the face, neck, and upper extremities in the summer. the ptcl was previously treated with chemotherapy; however, duvelisib was initiated after repeat imaging and lymph node biopsy revealed progressive disease. one month after introducing duvelisib, the patient developed concurrent skin rash and transaminitis. within five days, the rash progressed in severity and duvelisib was held. physical examination revealed photo-accentuated erythematous papules coalescing into plaques on the face, chest, dorsal arms (figure 2a and 2b). a punch biopsy of her left forearm was performed, and histopathologic analysis demonstrated a perivascular and interstitial dermatitis with eosinophils (figure 2c and 2d). the patient was treated with topical triamcinolone, antihistamines, and an oral prednisone taper. within three weeks, the rash significantly improved and duvelisib was resumed at a lower dose. after resumption of duvelisib, the patient had persistent pruritus and xerosis, managed with oral antihistamines and topical emollients. her rash recurred three and a half months later, albeit with markedly decreased severity, and rapidly resolved with topical triamcinolone. she remains stable on duvelisib with complete tumor response. given temporal association with duvelisib initiation and recurrence with rechallenge, the patient was diagnosed with duvelisib-induced photo-accentuated morbilliform skin eruption. pi3k inhibitors block the pi3k/akt/mtor pathway, a signaling cascade that regulates cell proliferation, growth, motility, and survival through extracellular signaling. isoform-specific pi3k inhibitors are a subclass that take advantage of this pathway’s impact on oncogenesis.3 cutaneous adverse events are commonly observed, occurring in 17-45% of patients, varying per isoform target.4-6 though the majority of eruptions are mild, skin toxicities are the second most common grade 3 and 4 toxicity, per common terminology criteria for adverse events (ctcae) grading, for alpelisib and duvelisib.6 cutaneous eruptions related to pi3k inhibitors present variably and can develop days to months after drug initiation (table 1). a diffuse maculopapular rash with or without pruritus and xerosis is the most frequently reported skin manifestation; however phase i and ii trials did not characterize cutaneous reactions with specific descriptors.3 case reports have delineated various clinical presentations, including, but not limited to, eczematous, psoriasiform, and prp-like eruptions, as well as exfoliative dermatitis and stevensjohnson syndrome/toxic epidermal necrolysis.3,5,7-12 histopathology for specific eruptions largely resembles the clinical correlate, and non-specific eruptions commonly reveal perivascular and dermal infiltration by eosinophils and lymphocytes, discussion skin november 2020 volume 4 issue 6 copyright 2020 the national society for cutaneous medicine 590 with or without epidermal spongiosis.5 this report of two cases of pi3k inhibitor-induced rash adds photo-accentuated eruptions to the clinical presentations previously reported in the literature. the pathophysiology of these toxicities is attributed to the effects of pi3k inhibition on subsets of lymphocytes, including tregulatory cells and differentiation of th1 and th2 lymphocytes. disruption in immune regulation and self-tolerance thus results in toxicities of an autoimmune nature.1 of note, pi3k inhibitors are effective photosensitizing agents and demonstrated potential utility in photodynamic therapy for cancer, thereby suggesting a possible mechanism underlying the photo-accentuated cutaneous toxicity noted in this case series.13 according to ctcae guidelines, eruptions should be stratified by severity corresponding to body surface area involvement. lower grade toxicities can be managed with high potency topical corticosteroids and antihistamines, whereas severe and persistent toxicities require systemic corticosteroids and possible interruption of pi3k inhibitor therapy. notably, if therapy is interrupted, rechallenge at a lower dosage can be trialed. close monitoring is paramount, as one in four patients experience recurrence of cutaneous toxicity with resumption of therapy, as reflected in this case series.5 while pi3k inhibitors are currently approved for a narrow range of malignancies, ongoing clinical trials present promising data for future utility in treatment of multiple solid tumors. thus, the cutaneous toxicities of pi3k inhibitors merit recognition as the use of these agents expands.12 conflict of interest disclosures: none funding: none corresponding author: lauren guggina, md northwestern university feinberg school of medicine 676 north saint clair chicago, il 60611 email: lguggina@nm.org references: 1. greenwell ib, ip a, cohen jb. pi3k inhibitors: understanding toxicity mechanisms and management. oncology (williston park). 2017;31(11):821-828. 2. andre f, ciruelos e, rubovszky g, et al. alpelisib for pik3ca-mutated, hormone receptor-positive advanced breast cancer. n engl j med. 2019;380(20):1929-1940. 3. nunnery se, mayer ia. management of toxicity to isoform alpha-specific pi3k inhibitors. ann oncol. 2019;30 suppl 10:x21-x26. 4. flinn iw, patel m, oki y, et al. duvelisib, an oral dual pi3k-delta, gamma inhibitor, shows clinical activity in indolent non-hodgkin lymphoma in a phase 1 study. am j hematol. 2018;93(11):1311-1317. 5. ransohoff jd, kwong by. cutaneous adverse events of targeted therapies for hematolymphoid malignancies. clin lymphoma myeloma leuk. 2017;17(12):834-851. 6. horwitz sm, koch r, porcu p, et al. activity of the pi3k-delta,gamma inhibitor duvelisib in a phase 1 trial and preclinical models of t-cell lymphoma. blood. 2018;131(8):888-898. 7. gabriel jg, kapila a, gonzalez-estrada a. a severe case of cutaneous adverse drug reaction secondary to a novice drug: idelalisib. j investig med high impact case rep. 2017;5(2):2324709617711463. 8. hammami mb, al-taee a, meeks m, et al. idelalisibinduced colitis and skin eruption mimicking graftversus-host disease. clin j gastroenterol. 2017;10(2):142-146. 9. huilaja l, lindgren o, soronen m, siitonen t, tasanen k. a slowly developed severe cutaneous adverse reaction to idelalisib. j eur acad dermatol venereol. 2018;32(5):e192-e193. 10. machan s, plaza c, perez-gonzalez y, rodriguezpinilla m, requena l, cordoba r. management of psoriasis-like rash associated with idelalisib monotherapy in a patient with refractory follicular lymphoma: a case report. j med case rep. 2020;14(1):35. 11. dewan ak, sowerby l, jadeja s, et al. pityriasis rubra pilaris-like erythroderma secondary to phosphoinositide 3-kinase inhibition. clin exp dermatol. 2018;43(8):890-894. 12. dewan ak, gupta s, bach dq, et al. psoriasiform eruptions secondary to phosphoinositide 3-kinase inhibition. jaad case rep. 2019;5(5):401-405. 13. hayashida y, ikeda y, sawada k, et al. invention of a novel photodynamic therapy for tumors using a photosensitizing pi3k inhibitor. int j cancer. 2016;139(3):700-711. mailto:lguggina@nm.org mailto:lguggina@nm.org synopsis • in the phase 3 clinical trials poetyk pso-1 and pso-2, deucravacitinib was compared for effi cacy and safety with placebo and apremilast in the treatment of patients with moderate to severe plaque psoriasis1 — deucravacitinib is an oral, selective, allosteric tyrosine kinase 2 (tyk2) inhibitor approved by the us food and drug administration for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy — in each clinical trial, greater proportions of patients who received deucravacitinib achieved ≥75% reduction from baseline in the psoriasis area and severity index score (pasi 75)1 and static physician’s global assessment scores of 0 or 1 (spga 0/1),1 and showed meaningful improvements on psoriasis symptoms and signs diary (pssd) total scores (≥25 points)2 and dermatology life quality index (dlqi) total scores (≥4 points)3 compared with patients receiving placebo or apremilast • in this post hoc analysis of data pooled from both trials, clinical and patient-reported outcomes (pros) were found to be correlated • when analyzed by the deucravacitinib or placebo treatment arm, greater proportions of patients who received deucravacitinib reported symptom reduction and improved quality of life, both in patients who did and who did not achieve pasi 75 and spga 0/1 responses objective • to explore the correlations between responses on clinical and pro measures in pooled data from poetyk pso-1 and pso-2 methods • in poetyk pso-1 (n = 666) and pso-2 (n = 1020) adults (aged ≥18 years) with moderate to severe psoriasis were randomized 2:1:1 to deucravacitinib 6 mg once daily, placebo, or apremilast 30 mg twice daily — at week 16 in each trial, patients who received placebo crossed over to deucravacitinib • using data pooled from both trials, we evaluated the correlation between responses measured by pasi and spga on one hand, and the pro measures pssd (≥25 points)2 and dlqi (≥4 points)3 on the other — the analysis populations for the pssd and dlqi included all patients from the full analysis set who completed ≥1 item on the respective questionnaire at baseline and ≥1 post-baseline visit • at baseline, 1659 patients had a dlqi score recorded and 1553 had a pssd score recorded • spearman correlation coeffi cients between clinical and pro score changes from baseline to week 16 were calculated with all treatment groups combined • mean pssd and dlqi scores were determined within relative pasi and spga response levels • the proportions of patients achieving meaningful improvement (ie, response) in pssd total scores and on the dlqi were summarized by whether they did or did not achieve pasi 75 and spga 0/1, and were further analyzed by treatment arm — results are reported for patients receiving deucravacitinib or placebo outcome measures • pasi — clinician evaluated — range: 0–72, with higher scores indicating more severe disease • spga — clinician evaluated — range: 0 (clear) to 4 (severe) • pssd — patient rated — 5 skin symptoms (itch, tightness, burning, stinging, and pain) and 6 skin signs (dryness, cracking, scaling, shedding/fl aking, redness, and bleeding) associated with psoriasis were rated 0 (absent) to 10 (worst imaginable); averages within each domain were multiplied by 10, then averaged across both domains to obtain a total score — range: 0–100, with higher scores indicating heavier disease burden • dlqi — patient rated — 10 questions that assess the extent to which skin disease affects patients’ lives — range: 0–30, with higher scores indicating more severe impact of disease results correlations between clinical and pro measures • at week 16, change from baseline in relative pasi score was correlated with changes in the pssd total score (spearman’s rank correlation coeffi cient [r s ] = 0.536) and dlqi total score (r s = 0.421) in the total study population • at week 16, change from baseline in spga score was correlated with changes in the pssd total score (r s = 0.496) and dlqi total score (r s = 0.380) in the total study population • higher pasi or spga response was associated with greater pssd and dlqi responses at weeks 16, 24, and 52 in the total study population (figures 1–4) figure 1. pssd total score change from baseline by pasi response group (treatment arms and trials pooled, n = 1536) –50 –45 –40 –35 –30 –25 –20 –15 –10 –5 0 week 16 week 24 week 52 p ss d c h an ge f ro m b as e li n e a pasi <50 pasi 50–74 pasi 75–89 pasi 90–99 pasi 100 aat baseline, the mean pssd total score (sd) was 54.4 (23.30) in the deucravacitinib arm, 53.1 (23.09) in the placebo arm, and 55.7 (22.90) in the apremilast arm. pasi 50–100, 50%–100% improvement from baseline in the psoriasis area and severity index score; pssd, psoriasis symptoms and signs diary. figure 2. dlqi change from baseline by pasi response group (treatment arms and trials pooled, n = 1643) –14 –12 –10 –8 –6 –4 –2 0 week 16 week 24 week 52 d lq i ch an ge f ro m b as e li n e a pasi <50 pasi 50–74 pasi 75–89 pasi 90–99 pasi 100 athe mean baseline dlqi score (sd) among all patients in the study population was 12.0 (6.7). dlqi, dermatology life quality index; pasi 50–100, 50%–100% improvement from baseline psoriasis area and severity index score. figure 3. pssd change from baseline by spgaa change group (treatment arms and trials pooled, n = 1536) –50 –40 –30 –20 –10 0 10 20 week 16 week 24 week 52 p ss d c h an ge f ro m b as e li n e spga +1 spga 0 spga –1 spga –2 spga –3 or more aat baseline, 1345 patients in the total study population had an spga score of 3, and 340 had an spga score of 4. one patient had an spga score of 2; this patient was randomized but not treated. the mean baseline pssd total score (sd) was 54.4 (23.30) in the deucravacitinib arm, 53.1 (23.09) in the placebo arm, and 55.7 (22.90) in the apremilast arm. pssd, psoriasis symptoms and signs diary; spga, static physician’s global assessment. figure 4. dlqi change from baseline by spgaa change group (treatment arms and trials pooled, n = 1643) week 16 week 24 –12 –10 –8 –6 –4 –2 0 2 week 52 d lq i ch an ge f ro m b as e li n e spga +1 spga 0 spga –1 spga –2 spga –3 or more aat baseline, 1345 patients in the total study population had an spga score of 3 and 340 had an spga score of 4. one patient had an spga score of 2; this patient was randomized but not treated. the mean baseline dlqi score (sd) among all patients in the study population was 12.0 (6.7). dlqi, dermatology life quality index; spga, static physician’s global assessment. pssd response by clinical response • at week 16, pssd total score response (≥25-point reduction from baseline) was reported by 64.8% and 65.3% of all patients across both trials who achieved pasi 75 (356/549) and/or spga 0/1 (330/505), respectively (table 1) — greater proportions of patients who received deucravacitinib and achieved clinical response reported pssd total score response (68.6% of patients who achieved pasi 75 and 68.7% of patients who achieved spga 0/1) compared with patients who received placebo (31.3% of patients who achieved pasi 75 and 37.0% of patients who achieved spga 0/1) (table 1) — on the pssd itch item, meaningful improvement (≥2 points) was reported by 80.8% of patients receiving deucravacitinib who achieved pasi 75 and 80.1% of deucravacitinib-treated patients who achieved spga 0/1, compared with 43.8% of patients receiving placebo who achieved pasi 75 and 48.1% of placebo-treated patients who achieved spga 0/1 (figure 5) • at week 16, 27.9% and 29.8% of all patients across both trials who did not achieve pasi 75 (188/674) and/or did not achieve spga 0/1 (214/718), respectively, nonetheless reported pssd total score response — greater proportions of patients who received deucravacitinib and did not achieve clinical response nonetheless reported pssd total score response (41.8% of patients who did not achieve pasi 75 and 44.1% of patients who did not achieve spga 0/1) compared with patients who received placebo (10.4% of patients who did not achieve pasi 75 and 10.3% who did not achieve spga 0/1) — on the pssd itch item, meaningful improvement was reported by 54.9% of patients receiving deucravacitinib who did not achieve pasi 75 compared with 22.0% of patients receiving placebo who did not achieve pasi 75 table 1. pssd response at week 16 in patients who achieved clinical response pssd domain total patients n = 1536 deucravacitinib n = 765 placebo n = 383 total score (≥25-point reduction), n/na (%) pasi 75 356/549 (64.8)b 264/385 (68.6) 10/32 (31.3) spga 0/1 330/505 (65.3)b 248/361 (68.7) 10/27 (37.0) symptom score (≥25-point reduction), n/na (%) pasi 75 323/549 (58.8)b 240/385 (62.3) 10/32 (31.3) spga 0/1 296/505 (58.6)b 223/361 (61.8) 8/27 (29.6) sign score (≥25-point reduction), n/na (%) pasi 75 383/549 (69.8)b 284/385 (73.8) 10/32 (31.3) spga 0/1 354/505 (70.1)b 267/361 (74.0) 10/27 (37.0) athe denominator represents the patients who achieved clinical response and who completed ≥1 pssd item at baseline and ≥1 pssd item at a post-baseline visit. btotal denominator includes patients who received apremilast. pasi 75, ≥75% improvement from baseline in psoriasis area and severity index score; pssd, psoriasis symptoms and signs diary; spga 0/1, static physician’s global assessment score of 0 or 1. figure 5. pssd individual item response at week 16 in patientsa who achieved clinical response 0 10 20 30 40 50 60 70 80 90 deucravacitinib (n = 765) placebo (n = 383) p at ie n ts , % 80.8 80.1 79.7 80.3 63.6 63.2 58.7 58.4 66.2 66.2 85.7 84.8 72.7 72.9 84.2 84.5 85.7 85.3 79.2 78.9 49.9 48.2 43.8 48.1 46.9 40.7 37.5 37.0 31.3 25.9 34.4 29.6 43.8 48.1 46.9 48.1 46.9 51.9 43.8 48.1 37.5 48.1 31.3 33.3 pasi 75 spga 0/1 pasi 75 spga 0/1 pasi 75 spga 0/1 pasi 75 spga 0/1 pasi 75 spga 0/1 pasi 75 spga 0/1 pasi 75 spga 0/1 pasi 75 spga 0/1 pasi 75 spga 0/1 pasi 75 spga 0/1 pasi 75 spga 0/1 itch (≥2 points) tightness (≥2 points) burning (≥2 points) stinging (≥2 points) pain (≥2 points) dryness (≥2 points) cracking (≥2 points) scaling (≥2 points) shedding/flaking (≥2 points) redness (≥2 points) bleeding (≥2 points) adenominators include patients who achieved clinical response and completed ≥1 pssd item at baseline and ≥1 pssd item at a post-baseline visit. pasi 75, 75% reduction from baseline in psoriasis area and severity index score; pssd, psoriasis symptoms and signs diary; spga 0/1, static physician’s global assessment score of 0 or 1. dlqi response by clinical response • at week 16, dlqi response (≥4-point reduction from baseline) was reported by 83.3% and 82.5% of all patients across both trials who achieved pasi 75 (553/664) and/or spga 0/1 (496/601), respectively (table 2) — greater proportions of patients who received deucravacitinib and achieved clinical response reported meaningful dlqi improvement (84.7% of patients who achieved pasi 75 and 83.3% of patients who achieved spga 0/1) compared with patients who received placebo (72.7% of patients who achieved pasi 75 and 70.6% of patients who achieved spga 0/1) • at week 16, 54.7% and 57.3% of all patients across both trials who did not achieve pasi 75 (444/811) and/or did not achieve spga 0/1 (501/874), respectively, nonetheless reported dlqi response — greater proportions of patients who received deucravacitinib and did not achieve clinical response nonetheless reported meaningful dlqi improvement (67.1% of patients who did not achieve pasi 75 and 70.8% of patients who did not achieve spga 0/1) compared with patients who received placebo (40.5% of patients who did not achieve pasi 75 and 41.7% who did not achieve spga 0/1) table 2. dlqi response at week 16 in patients who achieved clinical response dlqi ≥4-point reduction total patients n = 1643 deucravacitinib n = 824 placebo n = 409 pasi 75, n/na (%) 553/664 (83.3)b 393/464 (84.7) 32/44 (72.7) spga 0/1, n/na (%) 496/601 (82.5)b 359/431 (83.3) 24/34 (70.6) athe denominator includes the patients who achieved clinical response and completed ≥1 dlqi item at baseline and ≥1 dlqi item at a post-baseline visit. btotal denominator includes patients who received apremilast. dlqi, dermatology life quality index; pasi 75, ≥75% improvement from baseline in psoriasis area and severity index score; spga 0/1, static physician’s global assessment score of 0 or 1. conclusions • psoriasis skin clearance, symptom reduction, and improved patient quality of life were correlated in the poetyk pso-1 and pso-2 trials — this correlation is consistent with that determined in other studies4-7 • higher clinical response was associated with greater pro measure response • pro measures capture patient-perceived treatment benefi ts that may not be ascertained by measuring rates of skin clearance with clinical assessments alone4 — psoriasis bears symptoms, such as pruritus, for which there are no validated objective measures,8 or which are best assessed by patients themselves9 in order to evaluate treatment effi cacy — among patients who achieved pasi 75 at week 16, 80.8% of patients who received deucravacitinib reported meaningful itch improvement on the pssd compared with 43.8% of patients who received placebo • among patients with and without clinical response, greater proportions of patients treated with deucravacitinib recorded improvement in their self-reported symptoms, signs, and quality of life compared with patients treated with placebo references 1. warren rb, et al. ann rheum dis. 2022;81:1570-1571. 2. papp ka, et al. [poster] presented at the 30th congress of the european academy of dermatology and venereology (eadv); september 29–october 2, 2021; virtual meeting. 3. augustin m, et al. [poster] presented at the american academy of dermatology (aad) annual meeting; march 25–29, 2022; boston, ma. 4. armstrong aw, et al. am j clin dermatol. 2019;20:155-164. 5. loft nd, et al. acta derm venereol. 2019;99:1224-1230. 6. schäfer i, et al. eur j dermatol. 2010;20:62-67. 7. thaçi d, et al. dermatol ther (heidelb). 2022;12:495-510. 8. price a, cohen de. dermatitis. 2014;225:334-344. 9. armstrong aw, et al. j dermatol treat. 2019;30:27-34. acknowledgments • this study was sponsored by bristol myers squibb • medical writing and editorial assistance was provided by eleanor bush, ma, of peloton advantage, llc, an open health company, and funded by bristol myers squibb disclosures • awa: grants and personal fees: abbvie, bristol myers squibb, eli lilly, janssen, leo pharma, and novartis; personal fees: boehringer ingelheim/parexel, celgene, dermavant, genentech, glaxosmithkline, menlo therapeutics, merck, modernizing medicine, ortho dermatologics, pfi zer, regeneron, sanofi genzyme, science 37, sun pharma, and valeant; grants: dermira, kyowa hakko kirin, and ucb, outside the submitted work • kap: speakers bureau: abbvie, amgen, astellas, celgene, eli lilly, galderma, janssen, kyowa hakko kirin, leo pharma, merck sharp & dohme, novartis, pfi zer, and valeant; grant/research support: abbvie, akros, allergan, amgen, anacor, arcutis, astrazeneca, baxalta, boehringer ingelheim, bristol myers squibb, celgene, coherus, dermira, dow pharma, eli lilly, galderma, genentech, glaxosmithkline, janssen, kyowa hakko kirin, leo pharma, medimmune, meiji seika pharma, merck serono, novartis, pfi zer, regeneron, roche, sanofi genzyme, takeda, ucb, and valeant; consultant: abbvie, akros, amgen, arcutis, astellas, astrazeneca, baxalta, baxter, boehringer ingelheim, bristol myers squibb, can-fite, celgene, coherus, dermira, dow pharma, eli lilly, forward pharma, galderma, genentech, janssen, kyowa hakko kirin, leo pharma, meiji seika pharma, merck serono, merck sharp & dohme, mitsubishi pharma, novartis, pfi zer, regeneron, roche, sanofi genzyme, takeda, ucb, and valeant; honoraria: abbvie, akros, amgen, baxter, boehringer ingelheim, celgene, coherus, eli lilly, forward pharma, galderma, glaxosmithkline, janssen, kyowa hakko kirin, merck sharp & dohme, merck serono, novartis, pfi zer, takeda, ucb, and valeant; scientifi c offi cer/steering committee/advisory board: abbvie, akros, amgen, anacor, astellas, baxter, boehringer ingelheim, bristol myers squibb, celgene, dow pharma, eli lilly, galderma, janssen, kyowa hakko kirin, merck serono, merck sharp & dohme, novartis, pfi zer, regeneron, sanofi genzyme, and valeant • jz, bb, yz, rmk, and sb: employees and shareholders of bristol myers squibb • jlb and md: employees of clinical outcomes solutions, which has received consulting fees from bristol myers squibb • bs: consultant (honoraria): abbvie, almirall, amgen, arcutis, arena, aristea, asana, boehringer ingelheim, bristol myers squibb, connect biopharma, dermavant, eli lilly, equillium, glaxosmithkline, immunic therapeutics, janssen, leo pharma, maruho, meiji seika pharma, mindera, novartis, ortho dermatologics, pfi zer, regeneron, sanofi genzyme, sun pharma, ucb, ventyx biosciences, and vtv therapeutics; speaker: abbvie, eli lilly, janssen, and sanofi genzyme; co-scientifi c director (consulting fee): corevitas’ (corrona) psoriasis registry; investigator: abbvie, cara, corevitas’ (corrona) psoriasis registry, dermavant, dermira, and novartis deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, in moderate to severe plaque psoriasis: correlations between patient-reported outcomes and clinical responses in the phase 3 clinical trials poetyk pso-1 and poetyk pso-2 april w. armstrong,1 kim a. papp,2 joe zhuo,3 brandon becker,3 yichen zhong,3 jennifer l. beaumont,4 michael derosa,4 renata m. kisa,3 subhashis banerjee,3 bruce strober5,6 1keck school of medicine, university of southern california, los angeles, ca; 2probity medical research, waterloo, ontario, canada; 3bristol myers squibb, princeton, nj; 4clinical outcomes solutions, chicago, il; 5yale university, new haven, ct; 6central connecticut dermatology, cromwell, ct presented at the fall clinical dermatology conference; october 20–23, 2022; las vegas, nv this poster may not be reproduced without written permission from the authors.email for april w. armstrong, md, mph: aprilarmstrong@post.harvard.edu scientifi c content on demand to request a copy of this poster: scan qr code via a barcode reader application qr codes are valid for 30 days after the congress presentation date. synopsis • in the phase 3 clinical trials poetyk pso-1 and pso-2, deucravacitinib was compared for effi cacy and safety with placebo and apremilast in the treatment of patients with moderate to severe plaque psoriasis1 — deucravacitinib is an oral, selective, allosteric tyrosine kinase 2 (tyk2) inhibitor approved by the us food and drug administration for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy — in each clinical trial, greater proportions of patients who received deucravacitinib achieved ≥75% reduction from baseline in the psoriasis area and severity index score (pasi 75)1 and static physician’s global assessment scores of 0 or 1 (spga 0/1),1 and showed meaningful improvements on psoriasis symptoms and signs diary (pssd) total scores (≥25 points)2 and dermatology life quality index (dlqi) total scores (≥4 points)3 compared with patients receiving placebo or apremilast • in this post hoc analysis of data pooled from both trials, clinical and patient-reported outcomes (pros) were found to be correlated • when analyzed by the deucravacitinib or placebo treatment arm, greater proportions of patients who received deucravacitinib reported symptom reduction and improved quality of life, both in patients who did and who did not achieve pasi 75 and spga 0/1 responses objective • to explore the correlations between responses on clinical and pro measures in pooled data from poetyk pso-1 and pso-2 methods • in poetyk pso-1 (n = 666) and pso-2 (n = 1020) adults (aged ≥18 years) with moderate to severe psoriasis were randomized 2:1:1 to deucravacitinib 6 mg once daily, placebo, or apremilast 30 mg twice daily — at week 16 in each trial, patients who received placebo crossed over to deucravacitinib • using data pooled from both trials, we evaluated the correlation between responses measured by pasi and spga on one hand, and the pro measures pssd (≥25 points)2 and dlqi (≥4 points)3 on the other — the analysis populations for the pssd and dlqi included all patients from the full analysis set who completed ≥1 item on the respective questionnaire at baseline and ≥1 post-baseline visit • at baseline, 1659 patients had a dlqi score recorded and 1553 had a pssd score recorded • spearman correlation coeffi cients between clinical and pro score changes from baseline to week 16 were calculated with all treatment groups combined • mean pssd and dlqi scores were determined within relative pasi and spga response levels • the proportions of patients achieving meaningful improvement (ie, response) in pssd total scores and on the dlqi were summarized by whether they did or did not achieve pasi 75 and spga 0/1, and were further analyzed by treatment arm — results are reported for patients receiving deucravacitinib or placebo outcome measures • pasi — clinician evaluated — range: 0–72, with higher scores indicating more severe disease • spga — clinician evaluated — range: 0 (clear) to 4 (severe) • pssd — patient rated — 5 skin symptoms (itch, tightness, burning, stinging, and pain) and 6 skin signs (dryness, cracking, scaling, shedding/fl aking, redness, and bleeding) associated with psoriasis were rated 0 (absent) to 10 (worst imaginable); averages within each domain were multiplied by 10, then averaged across both domains to obtain a total score — range: 0–100, with higher scores indicating heavier disease burden • dlqi — patient rated — 10 questions that assess the extent to which skin disease affects patients’ lives — range: 0–30, with higher scores indicating more severe impact of disease results correlations between clinical and pro measures • at week 16, change from baseline in relative pasi score was correlated with changes in the pssd total score (spearman’s rank correlation coeffi cient [r s ] = 0.536) and dlqi total score (r s = 0.421) in the total study population • at week 16, change from baseline in spga score was correlated with changes in the pssd total score (r s = 0.496) and dlqi total score (r s = 0.380) in the total study population • higher pasi or spga response was associated with greater pssd and dlqi responses at weeks 16, 24, and 52 in the total study population (figures 1–4) figure 1. pssd total score change from baseline by pasi response group (treatment arms and trials pooled, n = 1536) –50 –45 –40 –35 –30 –25 –20 –15 –10 –5 0 week 16 week 24 week 52 p ss d c h an ge f ro m b as e li n e a pasi <50 pasi 50–74 pasi 75–89 pasi 90–99 pasi 100 aat baseline, the mean pssd total score (sd) was 54.4 (23.30) in the deucravacitinib arm, 53.1 (23.09) in the placebo arm, and 55.7 (22.90) in the apremilast arm. pasi 50–100, 50%–100% improvement from baseline in the psoriasis area and severity index score; pssd, psoriasis symptoms and signs diary. figure 2. dlqi change from baseline by pasi response group (treatment arms and trials pooled, n = 1643) –14 –12 –10 –8 –6 –4 –2 0 week 16 week 24 week 52 d lq i ch an ge f ro m b as e li n e a pasi <50 pasi 50–74 pasi 75–89 pasi 90–99 pasi 100 athe mean baseline dlqi score (sd) among all patients in the study population was 12.0 (6.7). dlqi, dermatology life quality index; pasi 50–100, 50%–100% improvement from baseline psoriasis area and severity index score. figure 3. pssd change from baseline by spgaa change group (treatment arms and trials pooled, n = 1536) –50 –40 –30 –20 –10 0 10 20 week 16 week 24 week 52 p ss d c h an ge f ro m b as e li n e spga +1 spga 0 spga –1 spga –2 spga –3 or more aat baseline, 1345 patients in the total study population had an spga score of 3, and 340 had an spga score of 4. one patient had an spga score of 2; this patient was randomized but not treated. the mean baseline pssd total score (sd) was 54.4 (23.30) in the deucravacitinib arm, 53.1 (23.09) in the placebo arm, and 55.7 (22.90) in the apremilast arm. pssd, psoriasis symptoms and signs diary; spga, static physician’s global assessment. figure 4. dlqi change from baseline by spgaa change group (treatment arms and trials pooled, n = 1643) week 16 week 24 –12 –10 –8 –6 –4 –2 0 2 week 52 d lq i ch an ge f ro m b as e li n e spga +1 spga 0 spga –1 spga –2 spga –3 or more aat baseline, 1345 patients in the total study population had an spga score of 3 and 340 had an spga score of 4. one patient had an spga score of 2; this patient was randomized but not treated. the mean baseline dlqi score (sd) among all patients in the study population was 12.0 (6.7). dlqi, dermatology life quality index; spga, static physician’s global assessment. pssd response by clinical response • at week 16, pssd total score response (≥25-point reduction from baseline) was reported by 64.8% and 65.3% of all patients across both trials who achieved pasi 75 (356/549) and/or spga 0/1 (330/505), respectively (table 1) — greater proportions of patients who received deucravacitinib and achieved clinical response reported pssd total score response (68.6% of patients who achieved pasi 75 and 68.7% of patients who achieved spga 0/1) compared with patients who received placebo (31.3% of patients who achieved pasi 75 and 37.0% of patients who achieved spga 0/1) (table 1) — on the pssd itch item, meaningful improvement (≥2 points) was reported by 80.8% of patients receiving deucravacitinib who achieved pasi 75 and 80.1% of deucravacitinib-treated patients who achieved spga 0/1, compared with 43.8% of patients receiving placebo who achieved pasi 75 and 48.1% of placebo-treated patients who achieved spga 0/1 (figure 5) • at week 16, 27.9% and 29.8% of all patients across both trials who did not achieve pasi 75 (188/674) and/or did not achieve spga 0/1 (214/718), respectively, nonetheless reported pssd total score response — greater proportions of patients who received deucravacitinib and did not achieve clinical response nonetheless reported pssd total score response (41.8% of patients who did not achieve pasi 75 and 44.1% of patients who did not achieve spga 0/1) compared with patients who received placebo (10.4% of patients who did not achieve pasi 75 and 10.3% who did not achieve spga 0/1) — on the pssd itch item, meaningful improvement was reported by 54.9% of patients receiving deucravacitinib who did not achieve pasi 75 compared with 22.0% of patients receiving placebo who did not achieve pasi 75 table 1. pssd response at week 16 in patients who achieved clinical response pssd domain total patients n = 1536 deucravacitinib n = 765 placebo n = 383 total score (≥25-point reduction), n/na (%) pasi 75 356/549 (64.8)b 264/385 (68.6) 10/32 (31.3) spga 0/1 330/505 (65.3)b 248/361 (68.7) 10/27 (37.0) symptom score (≥25-point reduction), n/na (%) pasi 75 323/549 (58.8)b 240/385 (62.3) 10/32 (31.3) spga 0/1 296/505 (58.6)b 223/361 (61.8) 8/27 (29.6) sign score (≥25-point reduction), n/na (%) pasi 75 383/549 (69.8)b 284/385 (73.8) 10/32 (31.3) spga 0/1 354/505 (70.1)b 267/361 (74.0) 10/27 (37.0) athe denominator represents the patients who achieved clinical response and who completed ≥1 pssd item at baseline and ≥1 pssd item at a post-baseline visit. btotal denominator includes patients who received apremilast. pasi 75, ≥75% improvement from baseline in psoriasis area and severity index score; pssd, psoriasis symptoms and signs diary; spga 0/1, static physician’s global assessment score of 0 or 1. figure 5. pssd individual item response at week 16 in patientsa who achieved clinical response 0 10 20 30 40 50 60 70 80 90 deucravacitinib (n = 765) placebo (n = 383) p at ie n ts , % 80.8 80.1 79.7 80.3 63.6 63.2 58.7 58.4 66.2 66.2 85.7 84.8 72.7 72.9 84.2 84.5 85.7 85.3 79.2 78.9 49.9 48.2 43.8 48.1 46.9 40.7 37.5 37.0 31.3 25.9 34.4 29.6 43.8 48.1 46.9 48.1 46.9 51.9 43.8 48.1 37.5 48.1 31.3 33.3 pasi 75 spga 0/1 pasi 75 spga 0/1 pasi 75 spga 0/1 pasi 75 spga 0/1 pasi 75 spga 0/1 pasi 75 spga 0/1 pasi 75 spga 0/1 pasi 75 spga 0/1 pasi 75 spga 0/1 pasi 75 spga 0/1 pasi 75 spga 0/1 itch (≥2 points) tightness (≥2 points) burning (≥2 points) stinging (≥2 points) pain (≥2 points) dryness (≥2 points) cracking (≥2 points) scaling (≥2 points) shedding/flaking (≥2 points) redness (≥2 points) bleeding (≥2 points) adenominators include patients who achieved clinical response and completed ≥1 pssd item at baseline and ≥1 pssd item at a post-baseline visit. pasi 75, 75% reduction from baseline in psoriasis area and severity index score; pssd, psoriasis symptoms and signs diary; spga 0/1, static physician’s global assessment score of 0 or 1. dlqi response by clinical response • at week 16, dlqi response (≥4-point reduction from baseline) was reported by 83.3% and 82.5% of all patients across both trials who achieved pasi 75 (553/664) and/or spga 0/1 (496/601), respectively (table 2) — greater proportions of patients who received deucravacitinib and achieved clinical response reported meaningful dlqi improvement (84.7% of patients who achieved pasi 75 and 83.3% of patients who achieved spga 0/1) compared with patients who received placebo (72.7% of patients who achieved pasi 75 and 70.6% of patients who achieved spga 0/1) • at week 16, 54.7% and 57.3% of all patients across both trials who did not achieve pasi 75 (444/811) and/or did not achieve spga 0/1 (501/874), respectively, nonetheless reported dlqi response — greater proportions of patients who received deucravacitinib and did not achieve clinical response nonetheless reported meaningful dlqi improvement (67.1% of patients who did not achieve pasi 75 and 70.8% of patients who did not achieve spga 0/1) compared with patients who received placebo (40.5% of patients who did not achieve pasi 75 and 41.7% who did not achieve spga 0/1) table 2. dlqi response at week 16 in patients who achieved clinical response dlqi ≥4-point reduction total patients n = 1643 deucravacitinib n = 824 placebo n = 409 pasi 75, n/na (%) 553/664 (83.3)b 393/464 (84.7) 32/44 (72.7) spga 0/1, n/na (%) 496/601 (82.5)b 359/431 (83.3) 24/34 (70.6) athe denominator includes the patients who achieved clinical response and completed ≥1 dlqi item at baseline and ≥1 dlqi item at a post-baseline visit. btotal denominator includes patients who received apremilast. dlqi, dermatology life quality index; pasi 75, ≥75% improvement from baseline in psoriasis area and severity index score; spga 0/1, static physician’s global assessment score of 0 or 1. conclusions • psoriasis skin clearance, symptom reduction, and improved patient quality of life were correlated in the poetyk pso-1 and pso-2 trials — this correlation is consistent with that determined in other studies4-7 • higher clinical response was associated with greater pro measure response • pro measures capture patient-perceived treatment benefi ts that may not be ascertained by measuring rates of skin clearance with clinical assessments alone4 — psoriasis bears symptoms, such as pruritus, for which there are no validated objective measures,8 or which are best assessed by patients themselves9 in order to evaluate treatment effi cacy — among patients who achieved pasi 75 at week 16, 80.8% of patients who received deucravacitinib reported meaningful itch improvement on the pssd compared with 43.8% of patients who received placebo • among patients with and without clinical response, greater proportions of patients treated with deucravacitinib recorded improvement in their self-reported symptoms, signs, and quality of life compared with patients treated with placebo references 1. warren rb, et al. ann rheum dis. 2022;81:1570-1571. 2. papp ka, et al. [poster] presented at the 30th congress of the european academy of dermatology and venereology (eadv); september 29–october 2, 2021; virtual meeting. 3. augustin m, et al. [poster] presented at the american academy of dermatology (aad) annual meeting; march 25–29, 2022; boston, ma. 4. armstrong aw, et al. am j clin dermatol. 2019;20:155-164. 5. loft nd, et al. acta derm venereol. 2019;99:1224-1230. 6. schäfer i, et al. eur j dermatol. 2010;20:62-67. 7. thaçi d, et al. dermatol ther (heidelb). 2022;12:495-510. 8. price a, cohen de. dermatitis. 2014;225:334-344. 9. armstrong aw, et al. j dermatol treat. 2019;30:27-34. acknowledgments • this study was sponsored by bristol myers squibb • medical writing and editorial assistance was provided by eleanor bush, ma, of peloton advantage, llc, an open health company, and funded by bristol myers squibb disclosures • awa: grants and personal fees: abbvie, bristol myers squibb, eli lilly, janssen, leo pharma, and novartis; personal fees: boehringer ingelheim/parexel, celgene, dermavant, genentech, glaxosmithkline, menlo therapeutics, merck, modernizing medicine, ortho dermatologics, pfi zer, regeneron, sanofi genzyme, science 37, sun pharma, and valeant; grants: dermira, kyowa hakko kirin, and ucb, outside the submitted work • kap: speakers bureau: abbvie, amgen, astellas, celgene, eli lilly, galderma, janssen, kyowa hakko kirin, leo pharma, merck sharp & dohme, novartis, pfi zer, and valeant; grant/research support: abbvie, akros, allergan, amgen, anacor, arcutis, astrazeneca, baxalta, boehringer ingelheim, bristol myers squibb, celgene, coherus, dermira, dow pharma, eli lilly, galderma, genentech, glaxosmithkline, janssen, kyowa hakko kirin, leo pharma, medimmune, meiji seika pharma, merck serono, novartis, pfi zer, regeneron, roche, sanofi genzyme, takeda, ucb, and valeant; consultant: abbvie, akros, amgen, arcutis, astellas, astrazeneca, baxalta, baxter, boehringer ingelheim, bristol myers squibb, can-fite, celgene, coherus, dermira, dow pharma, eli lilly, forward pharma, galderma, genentech, janssen, kyowa hakko kirin, leo pharma, meiji seika pharma, merck serono, merck sharp & dohme, mitsubishi pharma, novartis, pfi zer, regeneron, roche, sanofi genzyme, takeda, ucb, and valeant; honoraria: abbvie, akros, amgen, baxter, boehringer ingelheim, celgene, coherus, eli lilly, forward pharma, galderma, glaxosmithkline, janssen, kyowa hakko kirin, merck sharp & dohme, merck serono, novartis, pfi zer, takeda, ucb, and valeant; scientifi c offi cer/steering committee/advisory board: abbvie, akros, amgen, anacor, astellas, baxter, boehringer ingelheim, bristol myers squibb, celgene, dow pharma, eli lilly, galderma, janssen, kyowa hakko kirin, merck serono, merck sharp & dohme, novartis, pfi zer, regeneron, sanofi genzyme, and valeant • jz, bb, yz, rmk, and sb: employees and shareholders of bristol myers squibb • jlb and md: employees of clinical outcomes solutions, which has received consulting fees from bristol myers squibb • bs: consultant (honoraria): abbvie, almirall, amgen, arcutis, arena, aristea, asana, boehringer ingelheim, bristol myers squibb, connect biopharma, dermavant, eli lilly, equillium, glaxosmithkline, immunic therapeutics, janssen, leo pharma, maruho, meiji seika pharma, mindera, novartis, ortho dermatologics, pfi zer, regeneron, sanofi genzyme, sun pharma, ucb, ventyx biosciences, and vtv therapeutics; speaker: abbvie, eli lilly, janssen, and sanofi genzyme; co-scientifi c director (consulting fee): corevitas’ (corrona) psoriasis registry; investigator: abbvie, cara, corevitas’ (corrona) psoriasis registry, dermavant, dermira, and novartis deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, in moderate to severe plaque psoriasis: correlations between patient-reported outcomes and clinical responses in the phase 3 clinical trials poetyk pso-1 and poetyk pso-2 april w. armstrong,1 kim a. papp,2 joe zhuo,3 brandon becker,3 yichen zhong,3 jennifer l. beaumont,4 michael derosa,4 renata m. kisa,3 subhashis banerjee,3 bruce strober5,6 1keck school of medicine, university of southern california, los angeles, ca; 2probity medical research, waterloo, ontario, canada; 3bristol myers squibb, princeton, nj; 4clinical outcomes solutions, chicago, il; 5yale university, new haven, ct; 6central connecticut dermatology, cromwell, ct presented at the fall clinical dermatology conference; october 20–23, 2022; las vegas, nv this poster may not be reproduced without written permission from the authors.email for april w. armstrong, md, mph: aprilarmstrong@post.harvard.edu scientifi c content on demand to request a copy of this poster: scan qr code via a barcode reader application qr codes are valid for 30 days after the congress presentation date. synopsis • in the phase 3 clinical trials poetyk pso-1 and pso-2, deucravacitinib was compared for effi cacy and safety with placebo and apremilast in the treatment of patients with moderate to severe plaque psoriasis1 — deucravacitinib is an oral, selective, allosteric tyrosine kinase 2 (tyk2) inhibitor approved by the us food and drug administration for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy — in each clinical trial, greater proportions of patients who received deucravacitinib achieved ≥75% reduction from baseline in the psoriasis area and severity index score (pasi 75)1 and static physician’s global assessment scores of 0 or 1 (spga 0/1),1 and showed meaningful improvements on psoriasis symptoms and signs diary (pssd) total scores (≥25 points)2 and dermatology life quality index (dlqi) total scores (≥4 points)3 compared with patients receiving placebo or apremilast • in this post hoc analysis of data pooled from both trials, clinical and patient-reported outcomes (pros) were found to be correlated • when analyzed by the deucravacitinib or placebo treatment arm, greater proportions of patients who received deucravacitinib reported symptom reduction and improved quality of life, both in patients who did and who did not achieve pasi 75 and spga 0/1 responses objective • to explore the correlations between responses on clinical and pro measures in pooled data from poetyk pso-1 and pso-2 methods • in poetyk pso-1 (n = 666) and pso-2 (n = 1020) adults (aged ≥18 years) with moderate to severe psoriasis were randomized 2:1:1 to deucravacitinib 6 mg once daily, placebo, or apremilast 30 mg twice daily — at week 16 in each trial, patients who received placebo crossed over to deucravacitinib • using data pooled from both trials, we evaluated the correlation between responses measured by pasi and spga on one hand, and the pro measures pssd (≥25 points)2 and dlqi (≥4 points)3 on the other — the analysis populations for the pssd and dlqi included all patients from the full analysis set who completed ≥1 item on the respective questionnaire at baseline and ≥1 post-baseline visit • at baseline, 1659 patients had a dlqi score recorded and 1553 had a pssd score recorded • spearman correlation coeffi cients between clinical and pro score changes from baseline to week 16 were calculated with all treatment groups combined • mean pssd and dlqi scores were determined within relative pasi and spga response levels • the proportions of patients achieving meaningful improvement (ie, response) in pssd total scores and on the dlqi were summarized by whether they did or did not achieve pasi 75 and spga 0/1, and were further analyzed by treatment arm — results are reported for patients receiving deucravacitinib or placebo outcome measures • pasi — clinician evaluated — range: 0–72, with higher scores indicating more severe disease • spga — clinician evaluated — range: 0 (clear) to 4 (severe) • pssd — patient rated — 5 skin symptoms (itch, tightness, burning, stinging, and pain) and 6 skin signs (dryness, cracking, scaling, shedding/fl aking, redness, and bleeding) associated with psoriasis were rated 0 (absent) to 10 (worst imaginable); averages within each domain were multiplied by 10, then averaged across both domains to obtain a total score — range: 0–100, with higher scores indicating heavier disease burden • dlqi — patient rated — 10 questions that assess the extent to which skin disease affects patients’ lives — range: 0–30, with higher scores indicating more severe impact of disease results correlations between clinical and pro measures • at week 16, change from baseline in relative pasi score was correlated with changes in the pssd total score (spearman’s rank correlation coeffi cient [r s ] = 0.536) and dlqi total score (r s = 0.421) in the total study population • at week 16, change from baseline in spga score was correlated with changes in the pssd total score (r s = 0.496) and dlqi total score (r s = 0.380) in the total study population • higher pasi or spga response was associated with greater pssd and dlqi responses at weeks 16, 24, and 52 in the total study population (figures 1–4) figure 1. pssd total score change from baseline by pasi response group (treatment arms and trials pooled, n = 1536) –50 –45 –40 –35 –30 –25 –20 –15 –10 –5 0 week 16 week 24 week 52 p ss d c h an ge f ro m b as e li n e a pasi <50 pasi 50–74 pasi 75–89 pasi 90–99 pasi 100 aat baseline, the mean pssd total score (sd) was 54.4 (23.30) in the deucravacitinib arm, 53.1 (23.09) in the placebo arm, and 55.7 (22.90) in the apremilast arm. pasi 50–100, 50%–100% improvement from baseline in the psoriasis area and severity index score; pssd, psoriasis symptoms and signs diary. figure 2. dlqi change from baseline by pasi response group (treatment arms and trials pooled, n = 1643) –14 –12 –10 –8 –6 –4 –2 0 week 16 week 24 week 52 d lq i ch an ge f ro m b as e li n e a pasi <50 pasi 50–74 pasi 75–89 pasi 90–99 pasi 100 athe mean baseline dlqi score (sd) among all patients in the study population was 12.0 (6.7). dlqi, dermatology life quality index; pasi 50–100, 50%–100% improvement from baseline psoriasis area and severity index score. figure 3. pssd change from baseline by spgaa change group (treatment arms and trials pooled, n = 1536) –50 –40 –30 –20 –10 0 10 20 week 16 week 24 week 52 p ss d c h an ge f ro m b as e li n e spga +1 spga 0 spga –1 spga –2 spga –3 or more aat baseline, 1345 patients in the total study population had an spga score of 3, and 340 had an spga score of 4. one patient had an spga score of 2; this patient was randomized but not treated. the mean baseline pssd total score (sd) was 54.4 (23.30) in the deucravacitinib arm, 53.1 (23.09) in the placebo arm, and 55.7 (22.90) in the apremilast arm. pssd, psoriasis symptoms and signs diary; spga, static physician’s global assessment. figure 4. dlqi change from baseline by spgaa change group (treatment arms and trials pooled, n = 1643) week 16 week 24 –12 –10 –8 –6 –4 –2 0 2 week 52 d lq i ch an ge f ro m b as e li n e spga +1 spga 0 spga –1 spga –2 spga –3 or more aat baseline, 1345 patients in the total study population had an spga score of 3 and 340 had an spga score of 4. one patient had an spga score of 2; this patient was randomized but not treated. the mean baseline dlqi score (sd) among all patients in the study population was 12.0 (6.7). dlqi, dermatology life quality index; spga, static physician’s global assessment. pssd response by clinical response • at week 16, pssd total score response (≥25-point reduction from baseline) was reported by 64.8% and 65.3% of all patients across both trials who achieved pasi 75 (356/549) and/or spga 0/1 (330/505), respectively (table 1) — greater proportions of patients who received deucravacitinib and achieved clinical response reported pssd total score response (68.6% of patients who achieved pasi 75 and 68.7% of patients who achieved spga 0/1) compared with patients who received placebo (31.3% of patients who achieved pasi 75 and 37.0% of patients who achieved spga 0/1) (table 1) — on the pssd itch item, meaningful improvement (≥2 points) was reported by 80.8% of patients receiving deucravacitinib who achieved pasi 75 and 80.1% of deucravacitinib-treated patients who achieved spga 0/1, compared with 43.8% of patients receiving placebo who achieved pasi 75 and 48.1% of placebo-treated patients who achieved spga 0/1 (figure 5) • at week 16, 27.9% and 29.8% of all patients across both trials who did not achieve pasi 75 (188/674) and/or did not achieve spga 0/1 (214/718), respectively, nonetheless reported pssd total score response — greater proportions of patients who received deucravacitinib and did not achieve clinical response nonetheless reported pssd total score response (41.8% of patients who did not achieve pasi 75 and 44.1% of patients who did not achieve spga 0/1) compared with patients who received placebo (10.4% of patients who did not achieve pasi 75 and 10.3% who did not achieve spga 0/1) — on the pssd itch item, meaningful improvement was reported by 54.9% of patients receiving deucravacitinib who did not achieve pasi 75 compared with 22.0% of patients receiving placebo who did not achieve pasi 75 table 1. pssd response at week 16 in patients who achieved clinical response pssd domain total patients n = 1536 deucravacitinib n = 765 placebo n = 383 total score (≥25-point reduction), n/na (%) pasi 75 356/549 (64.8)b 264/385 (68.6) 10/32 (31.3) spga 0/1 330/505 (65.3)b 248/361 (68.7) 10/27 (37.0) symptom score (≥25-point reduction), n/na (%) pasi 75 323/549 (58.8)b 240/385 (62.3) 10/32 (31.3) spga 0/1 296/505 (58.6)b 223/361 (61.8) 8/27 (29.6) sign score (≥25-point reduction), n/na (%) pasi 75 383/549 (69.8)b 284/385 (73.8) 10/32 (31.3) spga 0/1 354/505 (70.1)b 267/361 (74.0) 10/27 (37.0) athe denominator represents the patients who achieved clinical response and who completed ≥1 pssd item at baseline and ≥1 pssd item at a post-baseline visit. btotal denominator includes patients who received apremilast. pasi 75, ≥75% improvement from baseline in psoriasis area and severity index score; pssd, psoriasis symptoms and signs diary; spga 0/1, static physician’s global assessment score of 0 or 1. figure 5. pssd individual item response at week 16 in patientsa who achieved clinical response 0 10 20 30 40 50 60 70 80 90 deucravacitinib (n = 765) placebo (n = 383) p at ie n ts , % 80.8 80.1 79.7 80.3 63.6 63.2 58.7 58.4 66.2 66.2 85.7 84.8 72.7 72.9 84.2 84.5 85.7 85.3 79.2 78.9 49.9 48.2 43.8 48.1 46.9 40.7 37.5 37.0 31.3 25.9 34.4 29.6 43.8 48.1 46.9 48.1 46.9 51.9 43.8 48.1 37.5 48.1 31.3 33.3 pasi 75 spga 0/1 pasi 75 spga 0/1 pasi 75 spga 0/1 pasi 75 spga 0/1 pasi 75 spga 0/1 pasi 75 spga 0/1 pasi 75 spga 0/1 pasi 75 spga 0/1 pasi 75 spga 0/1 pasi 75 spga 0/1 pasi 75 spga 0/1 itch (≥2 points) tightness (≥2 points) burning (≥2 points) stinging (≥2 points) pain (≥2 points) dryness (≥2 points) cracking (≥2 points) scaling (≥2 points) shedding/flaking (≥2 points) redness (≥2 points) bleeding (≥2 points) adenominators include patients who achieved clinical response and completed ≥1 pssd item at baseline and ≥1 pssd item at a post-baseline visit. pasi 75, 75% reduction from baseline in psoriasis area and severity index score; pssd, psoriasis symptoms and signs diary; spga 0/1, static physician’s global assessment score of 0 or 1. dlqi response by clinical response • at week 16, dlqi response (≥4-point reduction from baseline) was reported by 83.3% and 82.5% of all patients across both trials who achieved pasi 75 (553/664) and/or spga 0/1 (496/601), respectively (table 2) — greater proportions of patients who received deucravacitinib and achieved clinical response reported meaningful dlqi improvement (84.7% of patients who achieved pasi 75 and 83.3% of patients who achieved spga 0/1) compared with patients who received placebo (72.7% of patients who achieved pasi 75 and 70.6% of patients who achieved spga 0/1) • at week 16, 54.7% and 57.3% of all patients across both trials who did not achieve pasi 75 (444/811) and/or did not achieve spga 0/1 (501/874), respectively, nonetheless reported dlqi response — greater proportions of patients who received deucravacitinib and did not achieve clinical response nonetheless reported meaningful dlqi improvement (67.1% of patients who did not achieve pasi 75 and 70.8% of patients who did not achieve spga 0/1) compared with patients who received placebo (40.5% of patients who did not achieve pasi 75 and 41.7% who did not achieve spga 0/1) table 2. dlqi response at week 16 in patients who achieved clinical response dlqi ≥4-point reduction total patients n = 1643 deucravacitinib n = 824 placebo n = 409 pasi 75, n/na (%) 553/664 (83.3)b 393/464 (84.7) 32/44 (72.7) spga 0/1, n/na (%) 496/601 (82.5)b 359/431 (83.3) 24/34 (70.6) athe denominator includes the patients who achieved clinical response and completed ≥1 dlqi item at baseline and ≥1 dlqi item at a post-baseline visit. btotal denominator includes patients who received apremilast. dlqi, dermatology life quality index; pasi 75, ≥75% improvement from baseline in psoriasis area and severity index score; spga 0/1, static physician’s global assessment score of 0 or 1. conclusions • psoriasis skin clearance, symptom reduction, and improved patient quality of life were correlated in the poetyk pso-1 and pso-2 trials — this correlation is consistent with that determined in other studies4-7 • higher clinical response was associated with greater pro measure response • pro measures capture patient-perceived treatment benefi ts that may not be ascertained by measuring rates of skin clearance with clinical assessments alone4 — psoriasis bears symptoms, such as pruritus, for which there are no validated objective measures,8 or which are best assessed by patients themselves9 in order to evaluate treatment effi cacy — among patients who achieved pasi 75 at week 16, 80.8% of patients who received deucravacitinib reported meaningful itch improvement on the pssd compared with 43.8% of patients who received placebo • among patients with and without clinical response, greater proportions of patients treated with deucravacitinib recorded improvement in their self-reported symptoms, signs, and quality of life compared with patients treated with placebo references 1. warren rb, et al. ann rheum dis. 2022;81:1570-1571. 2. papp ka, et al. [poster] presented at the 30th congress of the european academy of dermatology and venereology (eadv); september 29–october 2, 2021; virtual meeting. 3. augustin m, et al. [poster] presented at the american academy of dermatology (aad) annual meeting; march 25–29, 2022; boston, ma. 4. armstrong aw, et al. am j clin dermatol. 2019;20:155-164. 5. loft nd, et al. acta derm venereol. 2019;99:1224-1230. 6. schäfer i, et al. eur j dermatol. 2010;20:62-67. 7. thaçi d, et al. dermatol ther (heidelb). 2022;12:495-510. 8. price a, cohen de. dermatitis. 2014;225:334-344. 9. armstrong aw, et al. j dermatol treat. 2019;30:27-34. acknowledgments • this study was sponsored by bristol myers squibb • medical writing and editorial assistance was provided by eleanor bush, ma, of peloton advantage, llc, an open health company, and funded by bristol myers squibb disclosures • awa: grants and personal fees: abbvie, bristol myers squibb, eli lilly, janssen, leo pharma, and novartis; personal fees: boehringer ingelheim/parexel, celgene, dermavant, genentech, glaxosmithkline, menlo therapeutics, merck, modernizing medicine, ortho dermatologics, pfi zer, regeneron, sanofi genzyme, science 37, sun pharma, and valeant; grants: dermira, kyowa hakko kirin, and ucb, outside the submitted work • kap: speakers bureau: abbvie, amgen, astellas, celgene, eli lilly, galderma, janssen, kyowa hakko kirin, leo pharma, merck sharp & dohme, novartis, pfi zer, and valeant; grant/research support: abbvie, akros, allergan, amgen, anacor, arcutis, astrazeneca, baxalta, boehringer ingelheim, bristol myers squibb, celgene, coherus, dermira, dow pharma, eli lilly, galderma, genentech, glaxosmithkline, janssen, kyowa hakko kirin, leo pharma, medimmune, meiji seika pharma, merck serono, novartis, pfi zer, regeneron, roche, sanofi genzyme, takeda, ucb, and valeant; consultant: abbvie, akros, amgen, arcutis, astellas, astrazeneca, baxalta, baxter, boehringer ingelheim, bristol myers squibb, can-fite, celgene, coherus, dermira, dow pharma, eli lilly, forward pharma, galderma, genentech, janssen, kyowa hakko kirin, leo pharma, meiji seika pharma, merck serono, merck sharp & dohme, mitsubishi pharma, novartis, pfi zer, regeneron, roche, sanofi genzyme, takeda, ucb, and valeant; honoraria: abbvie, akros, amgen, baxter, boehringer ingelheim, celgene, coherus, eli lilly, forward pharma, galderma, glaxosmithkline, janssen, kyowa hakko kirin, merck sharp & dohme, merck serono, novartis, pfi zer, takeda, ucb, and valeant; scientifi c offi cer/steering committee/advisory board: abbvie, akros, amgen, anacor, astellas, baxter, boehringer ingelheim, bristol myers squibb, celgene, dow pharma, eli lilly, galderma, janssen, kyowa hakko kirin, merck serono, merck sharp & dohme, novartis, pfi zer, regeneron, sanofi genzyme, and valeant • jz, bb, yz, rmk, and sb: employees and shareholders of bristol myers squibb • jlb and md: employees of clinical outcomes solutions, which has received consulting fees from bristol myers squibb • bs: consultant (honoraria): abbvie, almirall, amgen, arcutis, arena, aristea, asana, boehringer ingelheim, bristol myers squibb, connect biopharma, dermavant, eli lilly, equillium, glaxosmithkline, immunic therapeutics, janssen, leo pharma, maruho, meiji seika pharma, mindera, novartis, ortho dermatologics, pfi zer, regeneron, sanofi genzyme, sun pharma, ucb, ventyx biosciences, and vtv therapeutics; speaker: abbvie, eli lilly, janssen, and sanofi genzyme; co-scientifi c director (consulting fee): corevitas’ (corrona) psoriasis registry; investigator: abbvie, cara, corevitas’ (corrona) psoriasis registry, dermavant, dermira, and novartis deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, in moderate to severe plaque psoriasis: correlations between patient-reported outcomes and clinical responses in the phase 3 clinical trials poetyk pso-1 and poetyk pso-2 april w. armstrong,1 kim a. papp,2 joe zhuo,3 brandon becker,3 yichen zhong,3 jennifer l. beaumont,4 michael derosa,4 renata m. kisa,3 subhashis banerjee,3 bruce strober5,6 1keck school of medicine, university of southern california, los angeles, ca; 2probity medical research, waterloo, ontario, canada; 3bristol myers squibb, princeton, nj; 4clinical outcomes solutions, chicago, il; 5yale university, new haven, ct; 6central connecticut dermatology, cromwell, ct presented at the fall clinical dermatology conference; october 20–23, 2022; las vegas, nv this poster may not be reproduced without written permission from the authors.email for april w. armstrong, md, mph: aprilarmstrong@post.harvard.edu scientifi c content on demand to request a copy of this poster: scan qr code via a barcode reader application qr codes are valid for 30 days after the congress presentation date. synopsis • in the phase 3 clinical trials poetyk pso-1 and pso-2, deucravacitinib was compared for effi cacy and safety with placebo and apremilast in the treatment of patients with moderate to severe plaque psoriasis1 — deucravacitinib is an oral, selective, allosteric tyrosine kinase 2 (tyk2) inhibitor approved by the us food and drug administration for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy — in each clinical trial, greater proportions of patients who received deucravacitinib achieved ≥75% reduction from baseline in the psoriasis area and severity index score (pasi 75)1 and static physician’s global assessment scores of 0 or 1 (spga 0/1),1 and showed meaningful improvements on psoriasis symptoms and signs diary (pssd) total scores (≥25 points)2 and dermatology life quality index (dlqi) total scores (≥4 points)3 compared with patients receiving placebo or apremilast • in this post hoc analysis of data pooled from both trials, clinical and patient-reported outcomes (pros) were found to be correlated • when analyzed by the deucravacitinib or placebo treatment arm, greater proportions of patients who received deucravacitinib reported symptom reduction and improved quality of life, both in patients who did and who did not achieve pasi 75 and spga 0/1 responses objective • to explore the correlations between responses on clinical and pro measures in pooled data from poetyk pso-1 and pso-2 methods • in poetyk pso-1 (n = 666) and pso-2 (n = 1020) adults (aged ≥18 years) with moderate to severe psoriasis were randomized 2:1:1 to deucravacitinib 6 mg once daily, placebo, or apremilast 30 mg twice daily — at week 16 in each trial, patients who received placebo crossed over to deucravacitinib • using data pooled from both trials, we evaluated the correlation between responses measured by pasi and spga on one hand, and the pro measures pssd (≥25 points)2 and dlqi (≥4 points)3 on the other — the analysis populations for the pssd and dlqi included all patients from the full analysis set who completed ≥1 item on the respective questionnaire at baseline and ≥1 post-baseline visit • at baseline, 1659 patients had a dlqi score recorded and 1553 had a pssd score recorded • spearman correlation coeffi cients between clinical and pro score changes from baseline to week 16 were calculated with all treatment groups combined • mean pssd and dlqi scores were determined within relative pasi and spga response levels • the proportions of patients achieving meaningful improvement (ie, response) in pssd total scores and on the dlqi were summarized by whether they did or did not achieve pasi 75 and spga 0/1, and were further analyzed by treatment arm — results are reported for patients receiving deucravacitinib or placebo outcome measures • pasi — clinician evaluated — range: 0–72, with higher scores indicating more severe disease • spga — clinician evaluated — range: 0 (clear) to 4 (severe) • pssd — patient rated — 5 skin symptoms (itch, tightness, burning, stinging, and pain) and 6 skin signs (dryness, cracking, scaling, shedding/fl aking, redness, and bleeding) associated with psoriasis were rated 0 (absent) to 10 (worst imaginable); averages within each domain were multiplied by 10, then averaged across both domains to obtain a total score — range: 0–100, with higher scores indicating heavier disease burden • dlqi — patient rated — 10 questions that assess the extent to which skin disease affects patients’ lives — range: 0–30, with higher scores indicating more severe impact of disease results correlations between clinical and pro measures • at week 16, change from baseline in relative pasi score was correlated with changes in the pssd total score (spearman’s rank correlation coeffi cient [r s ] = 0.536) and dlqi total score (r s = 0.421) in the total study population • at week 16, change from baseline in spga score was correlated with changes in the pssd total score (r s = 0.496) and dlqi total score (r s = 0.380) in the total study population • higher pasi or spga response was associated with greater pssd and dlqi responses at weeks 16, 24, and 52 in the total study population (figures 1–4) figure 1. pssd total score change from baseline by pasi response group (treatment arms and trials pooled, n = 1536) –50 –45 –40 –35 –30 –25 –20 –15 –10 –5 0 week 16 week 24 week 52 p ss d c h an ge f ro m b as e li n e a pasi <50 pasi 50–74 pasi 75–89 pasi 90–99 pasi 100 aat baseline, the mean pssd total score (sd) was 54.4 (23.30) in the deucravacitinib arm, 53.1 (23.09) in the placebo arm, and 55.7 (22.90) in the apremilast arm. pasi 50–100, 50%–100% improvement from baseline in the psoriasis area and severity index score; pssd, psoriasis symptoms and signs diary. figure 2. dlqi change from baseline by pasi response group (treatment arms and trials pooled, n = 1643) –14 –12 –10 –8 –6 –4 –2 0 week 16 week 24 week 52 d lq i ch an ge f ro m b as e li n e a pasi <50 pasi 50–74 pasi 75–89 pasi 90–99 pasi 100 athe mean baseline dlqi score (sd) among all patients in the study population was 12.0 (6.7). dlqi, dermatology life quality index; pasi 50–100, 50%–100% improvement from baseline psoriasis area and severity index score. figure 3. pssd change from baseline by spgaa change group (treatment arms and trials pooled, n = 1536) –50 –40 –30 –20 –10 0 10 20 week 16 week 24 week 52 p ss d c h an ge f ro m b as e li n e spga +1 spga 0 spga –1 spga –2 spga –3 or more aat baseline, 1345 patients in the total study population had an spga score of 3, and 340 had an spga score of 4. one patient had an spga score of 2; this patient was randomized but not treated. the mean baseline pssd total score (sd) was 54.4 (23.30) in the deucravacitinib arm, 53.1 (23.09) in the placebo arm, and 55.7 (22.90) in the apremilast arm. pssd, psoriasis symptoms and signs diary; spga, static physician’s global assessment. figure 4. dlqi change from baseline by spgaa change group (treatment arms and trials pooled, n = 1643) week 16 week 24 –12 –10 –8 –6 –4 –2 0 2 week 52 d lq i ch an ge f ro m b as e li n e spga +1 spga 0 spga –1 spga –2 spga –3 or more aat baseline, 1345 patients in the total study population had an spga score of 3 and 340 had an spga score of 4. one patient had an spga score of 2; this patient was randomized but not treated. the mean baseline dlqi score (sd) among all patients in the study population was 12.0 (6.7). dlqi, dermatology life quality index; spga, static physician’s global assessment. pssd response by clinical response • at week 16, pssd total score response (≥25-point reduction from baseline) was reported by 64.8% and 65.3% of all patients across both trials who achieved pasi 75 (356/549) and/or spga 0/1 (330/505), respectively (table 1) — greater proportions of patients who received deucravacitinib and achieved clinical response reported pssd total score response (68.6% of patients who achieved pasi 75 and 68.7% of patients who achieved spga 0/1) compared with patients who received placebo (31.3% of patients who achieved pasi 75 and 37.0% of patients who achieved spga 0/1) (table 1) — on the pssd itch item, meaningful improvement (≥2 points) was reported by 80.8% of patients receiving deucravacitinib who achieved pasi 75 and 80.1% of deucravacitinib-treated patients who achieved spga 0/1, compared with 43.8% of patients receiving placebo who achieved pasi 75 and 48.1% of placebo-treated patients who achieved spga 0/1 (figure 5) • at week 16, 27.9% and 29.8% of all patients across both trials who did not achieve pasi 75 (188/674) and/or did not achieve spga 0/1 (214/718), respectively, nonetheless reported pssd total score response — greater proportions of patients who received deucravacitinib and did not achieve clinical response nonetheless reported pssd total score response (41.8% of patients who did not achieve pasi 75 and 44.1% of patients who did not achieve spga 0/1) compared with patients who received placebo (10.4% of patients who did not achieve pasi 75 and 10.3% who did not achieve spga 0/1) — on the pssd itch item, meaningful improvement was reported by 54.9% of patients receiving deucravacitinib who did not achieve pasi 75 compared with 22.0% of patients receiving placebo who did not achieve pasi 75 table 1. pssd response at week 16 in patients who achieved clinical response pssd domain total patients n = 1536 deucravacitinib n = 765 placebo n = 383 total score (≥25-point reduction), n/na (%) pasi 75 356/549 (64.8)b 264/385 (68.6) 10/32 (31.3) spga 0/1 330/505 (65.3)b 248/361 (68.7) 10/27 (37.0) symptom score (≥25-point reduction), n/na (%) pasi 75 323/549 (58.8)b 240/385 (62.3) 10/32 (31.3) spga 0/1 296/505 (58.6)b 223/361 (61.8) 8/27 (29.6) sign score (≥25-point reduction), n/na (%) pasi 75 383/549 (69.8)b 284/385 (73.8) 10/32 (31.3) spga 0/1 354/505 (70.1)b 267/361 (74.0) 10/27 (37.0) athe denominator represents the patients who achieved clinical response and who completed ≥1 pssd item at baseline and ≥1 pssd item at a post-baseline visit. btotal denominator includes patients who received apremilast. pasi 75, ≥75% improvement from baseline in psoriasis area and severity index score; pssd, psoriasis symptoms and signs diary; spga 0/1, static physician’s global assessment score of 0 or 1. figure 5. pssd individual item response at week 16 in patientsa who achieved clinical response 0 10 20 30 40 50 60 70 80 90 deucravacitinib (n = 765) placebo (n = 383) p at ie n ts , % 80.8 80.1 79.7 80.3 63.6 63.2 58.7 58.4 66.2 66.2 85.7 84.8 72.7 72.9 84.2 84.5 85.7 85.3 79.2 78.9 49.9 48.2 43.8 48.1 46.9 40.7 37.5 37.0 31.3 25.9 34.4 29.6 43.8 48.1 46.9 48.1 46.9 51.9 43.8 48.1 37.5 48.1 31.3 33.3 pasi 75 spga 0/1 pasi 75 spga 0/1 pasi 75 spga 0/1 pasi 75 spga 0/1 pasi 75 spga 0/1 pasi 75 spga 0/1 pasi 75 spga 0/1 pasi 75 spga 0/1 pasi 75 spga 0/1 pasi 75 spga 0/1 pasi 75 spga 0/1 itch (≥2 points) tightness (≥2 points) burning (≥2 points) stinging (≥2 points) pain (≥2 points) dryness (≥2 points) cracking (≥2 points) scaling (≥2 points) shedding/flaking (≥2 points) redness (≥2 points) bleeding (≥2 points) adenominators include patients who achieved clinical response and completed ≥1 pssd item at baseline and ≥1 pssd item at a post-baseline visit. pasi 75, 75% reduction from baseline in psoriasis area and severity index score; pssd, psoriasis symptoms and signs diary; spga 0/1, static physician’s global assessment score of 0 or 1. dlqi response by clinical response • at week 16, dlqi response (≥4-point reduction from baseline) was reported by 83.3% and 82.5% of all patients across both trials who achieved pasi 75 (553/664) and/or spga 0/1 (496/601), respectively (table 2) — greater proportions of patients who received deucravacitinib and achieved clinical response reported meaningful dlqi improvement (84.7% of patients who achieved pasi 75 and 83.3% of patients who achieved spga 0/1) compared with patients who received placebo (72.7% of patients who achieved pasi 75 and 70.6% of patients who achieved spga 0/1) • at week 16, 54.7% and 57.3% of all patients across both trials who did not achieve pasi 75 (444/811) and/or did not achieve spga 0/1 (501/874), respectively, nonetheless reported dlqi response — greater proportions of patients who received deucravacitinib and did not achieve clinical response nonetheless reported meaningful dlqi improvement (67.1% of patients who did not achieve pasi 75 and 70.8% of patients who did not achieve spga 0/1) compared with patients who received placebo (40.5% of patients who did not achieve pasi 75 and 41.7% who did not achieve spga 0/1) table 2. dlqi response at week 16 in patients who achieved clinical response dlqi ≥4-point reduction total patients n = 1643 deucravacitinib n = 824 placebo n = 409 pasi 75, n/na (%) 553/664 (83.3)b 393/464 (84.7) 32/44 (72.7) spga 0/1, n/na (%) 496/601 (82.5)b 359/431 (83.3) 24/34 (70.6) athe denominator includes the patients who achieved clinical response and completed ≥1 dlqi item at baseline and ≥1 dlqi item at a post-baseline visit. btotal denominator includes patients who received apremilast. dlqi, dermatology life quality index; pasi 75, ≥75% improvement from baseline in psoriasis area and severity index score; spga 0/1, static physician’s global assessment score of 0 or 1. conclusions • psoriasis skin clearance, symptom reduction, and improved patient quality of life were correlated in the poetyk pso-1 and pso-2 trials — this correlation is consistent with that determined in other studies4-7 • higher clinical response was associated with greater pro measure response • pro measures capture patient-perceived treatment benefi ts that may not be ascertained by measuring rates of skin clearance with clinical assessments alone4 — psoriasis bears symptoms, such as pruritus, for which there are no validated objective measures,8 or which are best assessed by patients themselves9 in order to evaluate treatment effi cacy — among patients who achieved pasi 75 at week 16, 80.8% of patients who received deucravacitinib reported meaningful itch improvement on the pssd compared with 43.8% of patients who received placebo • among patients with and without clinical response, greater proportions of patients treated with deucravacitinib recorded improvement in their self-reported symptoms, signs, and quality of life compared with patients treated with placebo references 1. warren rb, et al. ann rheum dis. 2022;81:1570-1571. 2. papp ka, et al. [poster] presented at the 30th congress of the european academy of dermatology and venereology (eadv); september 29–october 2, 2021; virtual meeting. 3. augustin m, et al. [poster] presented at the american academy of dermatology (aad) annual meeting; march 25–29, 2022; boston, ma. 4. armstrong aw, et al. am j clin dermatol. 2019;20:155-164. 5. loft nd, et al. acta derm venereol. 2019;99:1224-1230. 6. schäfer i, et al. eur j dermatol. 2010;20:62-67. 7. thaçi d, et al. dermatol ther (heidelb). 2022;12:495-510. 8. price a, cohen de. dermatitis. 2014;225:334-344. 9. armstrong aw, et al. j dermatol treat. 2019;30:27-34. acknowledgments • this study was sponsored by bristol myers squibb • medical writing and editorial assistance was provided by eleanor bush, ma, of peloton advantage, llc, an open health company, and funded by bristol myers squibb disclosures • awa: grants and personal fees: abbvie, bristol myers squibb, eli lilly, janssen, leo pharma, and novartis; personal fees: boehringer ingelheim/parexel, celgene, dermavant, genentech, glaxosmithkline, menlo therapeutics, merck, modernizing medicine, ortho dermatologics, pfi zer, regeneron, sanofi genzyme, science 37, sun pharma, and valeant; grants: dermira, kyowa hakko kirin, and ucb, outside the submitted work • kap: speakers bureau: abbvie, amgen, astellas, celgene, eli lilly, galderma, janssen, kyowa hakko kirin, leo pharma, merck sharp & dohme, novartis, pfi zer, and valeant; grant/research support: abbvie, akros, allergan, amgen, anacor, arcutis, astrazeneca, baxalta, boehringer ingelheim, bristol myers squibb, celgene, coherus, dermira, dow pharma, eli lilly, galderma, genentech, glaxosmithkline, janssen, kyowa hakko kirin, leo pharma, medimmune, meiji seika pharma, merck serono, novartis, pfi zer, regeneron, roche, sanofi genzyme, takeda, ucb, and valeant; consultant: abbvie, akros, amgen, arcutis, astellas, astrazeneca, baxalta, baxter, boehringer ingelheim, bristol myers squibb, can-fite, celgene, coherus, dermira, dow pharma, eli lilly, forward pharma, galderma, genentech, janssen, kyowa hakko kirin, leo pharma, meiji seika pharma, merck serono, merck sharp & dohme, mitsubishi pharma, novartis, pfi zer, regeneron, roche, sanofi genzyme, takeda, ucb, and valeant; honoraria: abbvie, akros, amgen, baxter, boehringer ingelheim, celgene, coherus, eli lilly, forward pharma, galderma, glaxosmithkline, janssen, kyowa hakko kirin, merck sharp & dohme, merck serono, novartis, pfi zer, takeda, ucb, and valeant; scientifi c offi cer/steering committee/advisory board: abbvie, akros, amgen, anacor, astellas, baxter, boehringer ingelheim, bristol myers squibb, celgene, dow pharma, eli lilly, galderma, janssen, kyowa hakko kirin, merck serono, merck sharp & dohme, novartis, pfi zer, regeneron, sanofi genzyme, and valeant • jz, bb, yz, rmk, and sb: employees and shareholders of bristol myers squibb • jlb and md: employees of clinical outcomes solutions, which has received consulting fees from bristol myers squibb • bs: consultant (honoraria): abbvie, almirall, amgen, arcutis, arena, aristea, asana, boehringer ingelheim, bristol myers squibb, connect biopharma, dermavant, eli lilly, equillium, glaxosmithkline, immunic therapeutics, janssen, leo pharma, maruho, meiji seika pharma, mindera, novartis, ortho dermatologics, pfi zer, regeneron, sanofi genzyme, sun pharma, ucb, ventyx biosciences, and vtv therapeutics; speaker: abbvie, eli lilly, janssen, and sanofi genzyme; co-scientifi c director (consulting fee): corevitas’ (corrona) psoriasis registry; investigator: abbvie, cara, corevitas’ (corrona) psoriasis registry, dermavant, dermira, and novartis deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, in moderate to severe plaque psoriasis: correlations between patient-reported outcomes and clinical responses in the phase 3 clinical trials poetyk pso-1 and poetyk pso-2 april w. armstrong,1 kim a. papp,2 joe zhuo,3 brandon becker,3 yichen zhong,3 jennifer l. beaumont,4 michael derosa,4 renata m. kisa,3 subhashis banerjee,3 bruce strober5,6 1keck school of medicine, university of southern california, los angeles, ca; 2probity medical research, waterloo, ontario, canada; 3bristol myers squibb, princeton, nj; 4clinical outcomes solutions, chicago, il; 5yale university, new haven, ct; 6central connecticut dermatology, cromwell, ct presented at the fall clinical dermatology conference; october 20–23, 2022; las vegas, nv this poster may not be reproduced without written permission from the authors.email for april w. armstrong, md, mph: aprilarmstrong@post.harvard.edu scientifi c content on demand to request a copy of this poster: scan qr code via a barcode reader application qr codes are valid for 30 days after the congress presentation date. synopsis • in the phase 3 clinical trials poetyk pso-1 and pso-2, deucravacitinib was compared for effi cacy and safety with placebo and apremilast in the treatment of patients with moderate to severe plaque psoriasis1 — deucravacitinib is an oral, selective, allosteric tyrosine kinase 2 (tyk2) inhibitor approved by the us food and drug administration for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy — in each clinical trial, greater proportions of patients who received deucravacitinib achieved ≥75% reduction from baseline in the psoriasis area and severity index score (pasi 75)1 and static physician’s global assessment scores of 0 or 1 (spga 0/1),1 and showed meaningful improvements on psoriasis symptoms and signs diary (pssd) total scores (≥25 points)2 and dermatology life quality index (dlqi) total scores (≥4 points)3 compared with patients receiving placebo or apremilast • in this post hoc analysis of data pooled from both trials, clinical and patient-reported outcomes (pros) were found to be correlated • when analyzed by the deucravacitinib or placebo treatment arm, greater proportions of patients who received deucravacitinib reported symptom reduction and improved quality of life, both in patients who did and who did not achieve pasi 75 and spga 0/1 responses objective • to explore the correlations between responses on clinical and pro measures in pooled data from poetyk pso-1 and pso-2 methods • in poetyk pso-1 (n = 666) and pso-2 (n = 1020) adults (aged ≥18 years) with moderate to severe psoriasis were randomized 2:1:1 to deucravacitinib 6 mg once daily, placebo, or apremilast 30 mg twice daily — at week 16 in each trial, patients who received placebo crossed over to deucravacitinib • using data pooled from both trials, we evaluated the correlation between responses measured by pasi and spga on one hand, and the pro measures pssd (≥25 points)2 and dlqi (≥4 points)3 on the other — the analysis populations for the pssd and dlqi included all patients from the full analysis set who completed ≥1 item on the respective questionnaire at baseline and ≥1 post-baseline visit • at baseline, 1659 patients had a dlqi score recorded and 1553 had a pssd score recorded • spearman correlation coeffi cients between clinical and pro score changes from baseline to week 16 were calculated with all treatment groups combined • mean pssd and dlqi scores were determined within relative pasi and spga response levels • the proportions of patients achieving meaningful improvement (ie, response) in pssd total scores and on the dlqi were summarized by whether they did or did not achieve pasi 75 and spga 0/1, and were further analyzed by treatment arm — results are reported for patients receiving deucravacitinib or placebo outcome measures • pasi — clinician evaluated — range: 0–72, with higher scores indicating more severe disease • spga — clinician evaluated — range: 0 (clear) to 4 (severe) • pssd — patient rated — 5 skin symptoms (itch, tightness, burning, stinging, and pain) and 6 skin signs (dryness, cracking, scaling, shedding/fl aking, redness, and bleeding) associated with psoriasis were rated 0 (absent) to 10 (worst imaginable); averages within each domain were multiplied by 10, then averaged across both domains to obtain a total score — range: 0–100, with higher scores indicating heavier disease burden • dlqi — patient rated — 10 questions that assess the extent to which skin disease affects patients’ lives — range: 0–30, with higher scores indicating more severe impact of disease results correlations between clinical and pro measures • at week 16, change from baseline in relative pasi score was correlated with changes in the pssd total score (spearman’s rank correlation coeffi cient [r s ] = 0.536) and dlqi total score (r s = 0.421) in the total study population • at week 16, change from baseline in spga score was correlated with changes in the pssd total score (r s = 0.496) and dlqi total score (r s = 0.380) in the total study population • higher pasi or spga response was associated with greater pssd and dlqi responses at weeks 16, 24, and 52 in the total study population (figures 1–4) figure 1. pssd total score change from baseline by pasi response group (treatment arms and trials pooled, n = 1536) –50 –45 –40 –35 –30 –25 –20 –15 –10 –5 0 week 16 week 24 week 52 p ss d c h an ge f ro m b as e li n e a pasi <50 pasi 50–74 pasi 75–89 pasi 90–99 pasi 100 aat baseline, the mean pssd total score (sd) was 54.4 (23.30) in the deucravacitinib arm, 53.1 (23.09) in the placebo arm, and 55.7 (22.90) in the apremilast arm. pasi 50–100, 50%–100% improvement from baseline in the psoriasis area and severity index score; pssd, psoriasis symptoms and signs diary. figure 2. dlqi change from baseline by pasi response group (treatment arms and trials pooled, n = 1643) –14 –12 –10 –8 –6 –4 –2 0 week 16 week 24 week 52 d lq i ch an ge f ro m b as e li n e a pasi <50 pasi 50–74 pasi 75–89 pasi 90–99 pasi 100 athe mean baseline dlqi score (sd) among all patients in the study population was 12.0 (6.7). dlqi, dermatology life quality index; pasi 50–100, 50%–100% improvement from baseline psoriasis area and severity index score. figure 3. pssd change from baseline by spgaa change group (treatment arms and trials pooled, n = 1536) –50 –40 –30 –20 –10 0 10 20 week 16 week 24 week 52 p ss d c h an ge f ro m b as e li n e spga +1 spga 0 spga –1 spga –2 spga –3 or more aat baseline, 1345 patients in the total study population had an spga score of 3, and 340 had an spga score of 4. one patient had an spga score of 2; this patient was randomized but not treated. the mean baseline pssd total score (sd) was 54.4 (23.30) in the deucravacitinib arm, 53.1 (23.09) in the placebo arm, and 55.7 (22.90) in the apremilast arm. pssd, psoriasis symptoms and signs diary; spga, static physician’s global assessment. figure 4. dlqi change from baseline by spgaa change group (treatment arms and trials pooled, n = 1643) week 16 week 24 –12 –10 –8 –6 –4 –2 0 2 week 52 d lq i ch an ge f ro m b as e li n e spga +1 spga 0 spga –1 spga –2 spga –3 or more aat baseline, 1345 patients in the total study population had an spga score of 3 and 340 had an spga score of 4. one patient had an spga score of 2; this patient was randomized but not treated. the mean baseline dlqi score (sd) among all patients in the study population was 12.0 (6.7). dlqi, dermatology life quality index; spga, static physician’s global assessment. pssd response by clinical response • at week 16, pssd total score response (≥25-point reduction from baseline) was reported by 64.8% and 65.3% of all patients across both trials who achieved pasi 75 (356/549) and/or spga 0/1 (330/505), respectively (table 1) — greater proportions of patients who received deucravacitinib and achieved clinical response reported pssd total score response (68.6% of patients who achieved pasi 75 and 68.7% of patients who achieved spga 0/1) compared with patients who received placebo (31.3% of patients who achieved pasi 75 and 37.0% of patients who achieved spga 0/1) (table 1) — on the pssd itch item, meaningful improvement (≥2 points) was reported by 80.8% of patients receiving deucravacitinib who achieved pasi 75 and 80.1% of deucravacitinib-treated patients who achieved spga 0/1, compared with 43.8% of patients receiving placebo who achieved pasi 75 and 48.1% of placebo-treated patients who achieved spga 0/1 (figure 5) • at week 16, 27.9% and 29.8% of all patients across both trials who did not achieve pasi 75 (188/674) and/or did not achieve spga 0/1 (214/718), respectively, nonetheless reported pssd total score response — greater proportions of patients who received deucravacitinib and did not achieve clinical response nonetheless reported pssd total score response (41.8% of patients who did not achieve pasi 75 and 44.1% of patients who did not achieve spga 0/1) compared with patients who received placebo (10.4% of patients who did not achieve pasi 75 and 10.3% who did not achieve spga 0/1) — on the pssd itch item, meaningful improvement was reported by 54.9% of patients receiving deucravacitinib who did not achieve pasi 75 compared with 22.0% of patients receiving placebo who did not achieve pasi 75 table 1. pssd response at week 16 in patients who achieved clinical response pssd domain total patients n = 1536 deucravacitinib n = 765 placebo n = 383 total score (≥25-point reduction), n/na (%) pasi 75 356/549 (64.8)b 264/385 (68.6) 10/32 (31.3) spga 0/1 330/505 (65.3)b 248/361 (68.7) 10/27 (37.0) symptom score (≥25-point reduction), n/na (%) pasi 75 323/549 (58.8)b 240/385 (62.3) 10/32 (31.3) spga 0/1 296/505 (58.6)b 223/361 (61.8) 8/27 (29.6) sign score (≥25-point reduction), n/na (%) pasi 75 383/549 (69.8)b 284/385 (73.8) 10/32 (31.3) spga 0/1 354/505 (70.1)b 267/361 (74.0) 10/27 (37.0) athe denominator represents the patients who achieved clinical response and who completed ≥1 pssd item at baseline and ≥1 pssd item at a post-baseline visit. btotal denominator includes patients who received apremilast. pasi 75, ≥75% improvement from baseline in psoriasis area and severity index score; pssd, psoriasis symptoms and signs diary; spga 0/1, static physician’s global assessment score of 0 or 1. figure 5. pssd individual item response at week 16 in patientsa who achieved clinical response 0 10 20 30 40 50 60 70 80 90 deucravacitinib (n = 765) placebo (n = 383) p at ie n ts , % 80.8 80.1 79.7 80.3 63.6 63.2 58.7 58.4 66.2 66.2 85.7 84.8 72.7 72.9 84.2 84.5 85.7 85.3 79.2 78.9 49.9 48.2 43.8 48.1 46.9 40.7 37.5 37.0 31.3 25.9 34.4 29.6 43.8 48.1 46.9 48.1 46.9 51.9 43.8 48.1 37.5 48.1 31.3 33.3 pasi 75 spga 0/1 pasi 75 spga 0/1 pasi 75 spga 0/1 pasi 75 spga 0/1 pasi 75 spga 0/1 pasi 75 spga 0/1 pasi 75 spga 0/1 pasi 75 spga 0/1 pasi 75 spga 0/1 pasi 75 spga 0/1 pasi 75 spga 0/1 itch (≥2 points) tightness (≥2 points) burning (≥2 points) stinging (≥2 points) pain (≥2 points) dryness (≥2 points) cracking (≥2 points) scaling (≥2 points) shedding/flaking (≥2 points) redness (≥2 points) bleeding (≥2 points) adenominators include patients who achieved clinical response and completed ≥1 pssd item at baseline and ≥1 pssd item at a post-baseline visit. pasi 75, 75% reduction from baseline in psoriasis area and severity index score; pssd, psoriasis symptoms and signs diary; spga 0/1, static physician’s global assessment score of 0 or 1. dlqi response by clinical response • at week 16, dlqi response (≥4-point reduction from baseline) was reported by 83.3% and 82.5% of all patients across both trials who achieved pasi 75 (553/664) and/or spga 0/1 (496/601), respectively (table 2) — greater proportions of patients who received deucravacitinib and achieved clinical response reported meaningful dlqi improvement (84.7% of patients who achieved pasi 75 and 83.3% of patients who achieved spga 0/1) compared with patients who received placebo (72.7% of patients who achieved pasi 75 and 70.6% of patients who achieved spga 0/1) • at week 16, 54.7% and 57.3% of all patients across both trials who did not achieve pasi 75 (444/811) and/or did not achieve spga 0/1 (501/874), respectively, nonetheless reported dlqi response — greater proportions of patients who received deucravacitinib and did not achieve clinical response nonetheless reported meaningful dlqi improvement (67.1% of patients who did not achieve pasi 75 and 70.8% of patients who did not achieve spga 0/1) compared with patients who received placebo (40.5% of patients who did not achieve pasi 75 and 41.7% who did not achieve spga 0/1) table 2. dlqi response at week 16 in patients who achieved clinical response dlqi ≥4-point reduction total patients n = 1643 deucravacitinib n = 824 placebo n = 409 pasi 75, n/na (%) 553/664 (83.3)b 393/464 (84.7) 32/44 (72.7) spga 0/1, n/na (%) 496/601 (82.5)b 359/431 (83.3) 24/34 (70.6) athe denominator includes the patients who achieved clinical response and completed ≥1 dlqi item at baseline and ≥1 dlqi item at a post-baseline visit. btotal denominator includes patients who received apremilast. dlqi, dermatology life quality index; pasi 75, ≥75% improvement from baseline in psoriasis area and severity index score; spga 0/1, static physician’s global assessment score of 0 or 1. conclusions • psoriasis skin clearance, symptom reduction, and improved patient quality of life were correlated in the poetyk pso-1 and pso-2 trials — this correlation is consistent with that determined in other studies4-7 • higher clinical response was associated with greater pro measure response • pro measures capture patient-perceived treatment benefi ts that may not be ascertained by measuring rates of skin clearance with clinical assessments alone4 — psoriasis bears symptoms, such as pruritus, for which there are no validated objective measures,8 or which are best assessed by patients themselves9 in order to evaluate treatment effi cacy — among patients who achieved pasi 75 at week 16, 80.8% of patients who received deucravacitinib reported meaningful itch improvement on the pssd compared with 43.8% of patients who received placebo • among patients with and without clinical response, greater proportions of patients treated with deucravacitinib recorded improvement in their self-reported symptoms, signs, and quality of life compared with patients treated with placebo references 1. warren rb, et al. ann rheum dis. 2022;81:1570-1571. 2. papp ka, et al. [poster] presented at the 30th congress of the european academy of dermatology and venereology (eadv); september 29–october 2, 2021; virtual meeting. 3. augustin m, et al. [poster] presented at the american academy of dermatology (aad) annual meeting; march 25–29, 2022; boston, ma. 4. armstrong aw, et al. am j clin dermatol. 2019;20:155-164. 5. loft nd, et al. acta derm venereol. 2019;99:1224-1230. 6. schäfer i, et al. eur j dermatol. 2010;20:62-67. 7. thaçi d, et al. dermatol ther (heidelb). 2022;12:495-510. 8. price a, cohen de. dermatitis. 2014;225:334-344. 9. armstrong aw, et al. j dermatol treat. 2019;30:27-34. acknowledgments • this study was sponsored by bristol myers squibb • medical writing and editorial assistance was provided by eleanor bush, ma, of peloton advantage, llc, an open health company, and funded by bristol myers squibb disclosures • awa: grants and personal fees: abbvie, bristol myers squibb, eli lilly, janssen, leo pharma, and novartis; personal fees: boehringer ingelheim/parexel, celgene, dermavant, genentech, glaxosmithkline, menlo therapeutics, merck, modernizing medicine, ortho dermatologics, pfi zer, regeneron, sanofi genzyme, science 37, sun pharma, and valeant; grants: dermira, kyowa hakko kirin, and ucb, outside the submitted work • kap: speakers bureau: abbvie, amgen, astellas, celgene, eli lilly, galderma, janssen, kyowa hakko kirin, leo pharma, merck sharp & dohme, novartis, pfi zer, and valeant; grant/research support: abbvie, akros, allergan, amgen, anacor, arcutis, astrazeneca, baxalta, boehringer ingelheim, bristol myers squibb, celgene, coherus, dermira, dow pharma, eli lilly, galderma, genentech, glaxosmithkline, janssen, kyowa hakko kirin, leo pharma, medimmune, meiji seika pharma, merck serono, novartis, pfi zer, regeneron, roche, sanofi genzyme, takeda, ucb, and valeant; consultant: abbvie, akros, amgen, arcutis, astellas, astrazeneca, baxalta, baxter, boehringer ingelheim, bristol myers squibb, can-fite, celgene, coherus, dermira, dow pharma, eli lilly, forward pharma, galderma, genentech, janssen, kyowa hakko kirin, leo pharma, meiji seika pharma, merck serono, merck sharp & dohme, mitsubishi pharma, novartis, pfi zer, regeneron, roche, sanofi genzyme, takeda, ucb, and valeant; honoraria: abbvie, akros, amgen, baxter, boehringer ingelheim, celgene, coherus, eli lilly, forward pharma, galderma, glaxosmithkline, janssen, kyowa hakko kirin, merck sharp & dohme, merck serono, novartis, pfi zer, takeda, ucb, and valeant; scientifi c offi cer/steering committee/advisory board: abbvie, akros, amgen, anacor, astellas, baxter, boehringer ingelheim, bristol myers squibb, celgene, dow pharma, eli lilly, galderma, janssen, kyowa hakko kirin, merck serono, merck sharp & dohme, novartis, pfi zer, regeneron, sanofi genzyme, and valeant • jz, bb, yz, rmk, and sb: employees and shareholders of bristol myers squibb • jlb and md: employees of clinical outcomes solutions, which has received consulting fees from bristol myers squibb • bs: consultant (honoraria): abbvie, almirall, amgen, arcutis, arena, aristea, asana, boehringer ingelheim, bristol myers squibb, connect biopharma, dermavant, eli lilly, equillium, glaxosmithkline, immunic therapeutics, janssen, leo pharma, maruho, meiji seika pharma, mindera, novartis, ortho dermatologics, pfi zer, regeneron, sanofi genzyme, sun pharma, ucb, ventyx biosciences, and vtv therapeutics; speaker: abbvie, eli lilly, janssen, and sanofi genzyme; co-scientifi c director (consulting fee): corevitas’ (corrona) psoriasis registry; investigator: abbvie, cara, corevitas’ (corrona) psoriasis registry, dermavant, dermira, and novartis deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, in moderate to severe plaque psoriasis: correlations between patient-reported outcomes and clinical responses in the phase 3 clinical trials poetyk pso-1 and poetyk pso-2 april w. armstrong,1 kim a. papp,2 joe zhuo,3 brandon becker,3 yichen zhong,3 jennifer l. beaumont,4 michael derosa,4 renata m. kisa,3 subhashis banerjee,3 bruce strober5,6 1keck school of medicine, university of southern california, los angeles, ca; 2probity medical research, waterloo, ontario, canada; 3bristol myers squibb, princeton, nj; 4clinical outcomes solutions, chicago, il; 5yale university, new haven, ct; 6central connecticut dermatology, cromwell, ct presented at the fall clinical dermatology conference; october 20–23, 2022; las vegas, nv this poster may not be reproduced without written permission from the authors.email for april w. armstrong, md, mph: aprilarmstrong@post.harvard.edu scientifi c content on demand to request a copy of this poster: scan qr code via a barcode reader application qr codes are valid for 30 days after the congress presentation date. synopsis • in the phase 3 clinical trials poetyk pso-1 and pso-2, deucravacitinib was compared for effi cacy and safety with placebo and apremilast in the treatment of patients with moderate to severe plaque psoriasis1 — deucravacitinib is an oral, selective, allosteric tyrosine kinase 2 (tyk2) inhibitor approved by the us food and drug administration for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy — in each clinical trial, greater proportions of patients who received deucravacitinib achieved ≥75% reduction from baseline in the psoriasis area and severity index score (pasi 75)1 and static physician’s global assessment scores of 0 or 1 (spga 0/1),1 and showed meaningful improvements on psoriasis symptoms and signs diary (pssd) total scores (≥25 points)2 and dermatology life quality index (dlqi) total scores (≥4 points)3 compared with patients receiving placebo or apremilast • in this post hoc analysis of data pooled from both trials, clinical and patient-reported outcomes (pros) were found to be correlated • when analyzed by the deucravacitinib or placebo treatment arm, greater proportions of patients who received deucravacitinib reported symptom reduction and improved quality of life, both in patients who did and who did not achieve pasi 75 and spga 0/1 responses objective • to explore the correlations between responses on clinical and pro measures in pooled data from poetyk pso-1 and pso-2 methods • in poetyk pso-1 (n = 666) and pso-2 (n = 1020) adults (aged ≥18 years) with moderate to severe psoriasis were randomized 2:1:1 to deucravacitinib 6 mg once daily, placebo, or apremilast 30 mg twice daily — at week 16 in each trial, patients who received placebo crossed over to deucravacitinib • using data pooled from both trials, we evaluated the correlation between responses measured by pasi and spga on one hand, and the pro measures pssd (≥25 points)2 and dlqi (≥4 points)3 on the other — the analysis populations for the pssd and dlqi included all patients from the full analysis set who completed ≥1 item on the respective questionnaire at baseline and ≥1 post-baseline visit • at baseline, 1659 patients had a dlqi score recorded and 1553 had a pssd score recorded • spearman correlation coeffi cients between clinical and pro score changes from baseline to week 16 were calculated with all treatment groups combined • mean pssd and dlqi scores were determined within relative pasi and spga response levels • the proportions of patients achieving meaningful improvement (ie, response) in pssd total scores and on the dlqi were summarized by whether they did or did not achieve pasi 75 and spga 0/1, and were further analyzed by treatment arm — results are reported for patients receiving deucravacitinib or placebo outcome measures • pasi — clinician evaluated — range: 0–72, with higher scores indicating more severe disease • spga — clinician evaluated — range: 0 (clear) to 4 (severe) • pssd — patient rated — 5 skin symptoms (itch, tightness, burning, stinging, and pain) and 6 skin signs (dryness, cracking, scaling, shedding/fl aking, redness, and bleeding) associated with psoriasis were rated 0 (absent) to 10 (worst imaginable); averages within each domain were multiplied by 10, then averaged across both domains to obtain a total score — range: 0–100, with higher scores indicating heavier disease burden • dlqi — patient rated — 10 questions that assess the extent to which skin disease affects patients’ lives — range: 0–30, with higher scores indicating more severe impact of disease results correlations between clinical and pro measures • at week 16, change from baseline in relative pasi score was correlated with changes in the pssd total score (spearman’s rank correlation coeffi cient [r s ] = 0.536) and dlqi total score (r s = 0.421) in the total study population • at week 16, change from baseline in spga score was correlated with changes in the pssd total score (r s = 0.496) and dlqi total score (r s = 0.380) in the total study population • higher pasi or spga response was associated with greater pssd and dlqi responses at weeks 16, 24, and 52 in the total study population (figures 1–4) figure 1. pssd total score change from baseline by pasi response group (treatment arms and trials pooled, n = 1536) –50 –45 –40 –35 –30 –25 –20 –15 –10 –5 0 week 16 week 24 week 52 p ss d c h an ge f ro m b as e li n e a pasi <50 pasi 50–74 pasi 75–89 pasi 90–99 pasi 100 aat baseline, the mean pssd total score (sd) was 54.4 (23.30) in the deucravacitinib arm, 53.1 (23.09) in the placebo arm, and 55.7 (22.90) in the apremilast arm. pasi 50–100, 50%–100% improvement from baseline in the psoriasis area and severity index score; pssd, psoriasis symptoms and signs diary. figure 2. dlqi change from baseline by pasi response group (treatment arms and trials pooled, n = 1643) –14 –12 –10 –8 –6 –4 –2 0 week 16 week 24 week 52 d lq i ch an ge f ro m b as e li n e a pasi <50 pasi 50–74 pasi 75–89 pasi 90–99 pasi 100 athe mean baseline dlqi score (sd) among all patients in the study population was 12.0 (6.7). dlqi, dermatology life quality index; pasi 50–100, 50%–100% improvement from baseline psoriasis area and severity index score. figure 3. pssd change from baseline by spgaa change group (treatment arms and trials pooled, n = 1536) –50 –40 –30 –20 –10 0 10 20 week 16 week 24 week 52 p ss d c h an ge f ro m b as e li n e spga +1 spga 0 spga –1 spga –2 spga –3 or more aat baseline, 1345 patients in the total study population had an spga score of 3, and 340 had an spga score of 4. one patient had an spga score of 2; this patient was randomized but not treated. the mean baseline pssd total score (sd) was 54.4 (23.30) in the deucravacitinib arm, 53.1 (23.09) in the placebo arm, and 55.7 (22.90) in the apremilast arm. pssd, psoriasis symptoms and signs diary; spga, static physician’s global assessment. figure 4. dlqi change from baseline by spgaa change group (treatment arms and trials pooled, n = 1643) week 16 week 24 –12 –10 –8 –6 –4 –2 0 2 week 52 d lq i ch an ge f ro m b as e li n e spga +1 spga 0 spga –1 spga –2 spga –3 or more aat baseline, 1345 patients in the total study population had an spga score of 3 and 340 had an spga score of 4. one patient had an spga score of 2; this patient was randomized but not treated. the mean baseline dlqi score (sd) among all patients in the study population was 12.0 (6.7). dlqi, dermatology life quality index; spga, static physician’s global assessment. pssd response by clinical response • at week 16, pssd total score response (≥25-point reduction from baseline) was reported by 64.8% and 65.3% of all patients across both trials who achieved pasi 75 (356/549) and/or spga 0/1 (330/505), respectively (table 1) — greater proportions of patients who received deucravacitinib and achieved clinical response reported pssd total score response (68.6% of patients who achieved pasi 75 and 68.7% of patients who achieved spga 0/1) compared with patients who received placebo (31.3% of patients who achieved pasi 75 and 37.0% of patients who achieved spga 0/1) (table 1) — on the pssd itch item, meaningful improvement (≥2 points) was reported by 80.8% of patients receiving deucravacitinib who achieved pasi 75 and 80.1% of deucravacitinib-treated patients who achieved spga 0/1, compared with 43.8% of patients receiving placebo who achieved pasi 75 and 48.1% of placebo-treated patients who achieved spga 0/1 (figure 5) • at week 16, 27.9% and 29.8% of all patients across both trials who did not achieve pasi 75 (188/674) and/or did not achieve spga 0/1 (214/718), respectively, nonetheless reported pssd total score response — greater proportions of patients who received deucravacitinib and did not achieve clinical response nonetheless reported pssd total score response (41.8% of patients who did not achieve pasi 75 and 44.1% of patients who did not achieve spga 0/1) compared with patients who received placebo (10.4% of patients who did not achieve pasi 75 and 10.3% who did not achieve spga 0/1) — on the pssd itch item, meaningful improvement was reported by 54.9% of patients receiving deucravacitinib who did not achieve pasi 75 compared with 22.0% of patients receiving placebo who did not achieve pasi 75 table 1. pssd response at week 16 in patients who achieved clinical response pssd domain total patients n = 1536 deucravacitinib n = 765 placebo n = 383 total score (≥25-point reduction), n/na (%) pasi 75 356/549 (64.8)b 264/385 (68.6) 10/32 (31.3) spga 0/1 330/505 (65.3)b 248/361 (68.7) 10/27 (37.0) symptom score (≥25-point reduction), n/na (%) pasi 75 323/549 (58.8)b 240/385 (62.3) 10/32 (31.3) spga 0/1 296/505 (58.6)b 223/361 (61.8) 8/27 (29.6) sign score (≥25-point reduction), n/na (%) pasi 75 383/549 (69.8)b 284/385 (73.8) 10/32 (31.3) spga 0/1 354/505 (70.1)b 267/361 (74.0) 10/27 (37.0) athe denominator represents the patients who achieved clinical response and who completed ≥1 pssd item at baseline and ≥1 pssd item at a post-baseline visit. btotal denominator includes patients who received apremilast. pasi 75, ≥75% improvement from baseline in psoriasis area and severity index score; pssd, psoriasis symptoms and signs diary; spga 0/1, static physician’s global assessment score of 0 or 1. figure 5. pssd individual item response at week 16 in patientsa who achieved clinical response 0 10 20 30 40 50 60 70 80 90 deucravacitinib (n = 765) placebo (n = 383) p at ie n ts , % 80.8 80.1 79.7 80.3 63.6 63.2 58.7 58.4 66.2 66.2 85.7 84.8 72.7 72.9 84.2 84.5 85.7 85.3 79.2 78.9 49.9 48.2 43.8 48.1 46.9 40.7 37.5 37.0 31.3 25.9 34.4 29.6 43.8 48.1 46.9 48.1 46.9 51.9 43.8 48.1 37.5 48.1 31.3 33.3 pasi 75 spga 0/1 pasi 75 spga 0/1 pasi 75 spga 0/1 pasi 75 spga 0/1 pasi 75 spga 0/1 pasi 75 spga 0/1 pasi 75 spga 0/1 pasi 75 spga 0/1 pasi 75 spga 0/1 pasi 75 spga 0/1 pasi 75 spga 0/1 itch (≥2 points) tightness (≥2 points) burning (≥2 points) stinging (≥2 points) pain (≥2 points) dryness (≥2 points) cracking (≥2 points) scaling (≥2 points) shedding/flaking (≥2 points) redness (≥2 points) bleeding (≥2 points) adenominators include patients who achieved clinical response and completed ≥1 pssd item at baseline and ≥1 pssd item at a post-baseline visit. pasi 75, 75% reduction from baseline in psoriasis area and severity index score; pssd, psoriasis symptoms and signs diary; spga 0/1, static physician’s global assessment score of 0 or 1. dlqi response by clinical response • at week 16, dlqi response (≥4-point reduction from baseline) was reported by 83.3% and 82.5% of all patients across both trials who achieved pasi 75 (553/664) and/or spga 0/1 (496/601), respectively (table 2) — greater proportions of patients who received deucravacitinib and achieved clinical response reported meaningful dlqi improvement (84.7% of patients who achieved pasi 75 and 83.3% of patients who achieved spga 0/1) compared with patients who received placebo (72.7% of patients who achieved pasi 75 and 70.6% of patients who achieved spga 0/1) • at week 16, 54.7% and 57.3% of all patients across both trials who did not achieve pasi 75 (444/811) and/or did not achieve spga 0/1 (501/874), respectively, nonetheless reported dlqi response — greater proportions of patients who received deucravacitinib and did not achieve clinical response nonetheless reported meaningful dlqi improvement (67.1% of patients who did not achieve pasi 75 and 70.8% of patients who did not achieve spga 0/1) compared with patients who received placebo (40.5% of patients who did not achieve pasi 75 and 41.7% who did not achieve spga 0/1) table 2. dlqi response at week 16 in patients who achieved clinical response dlqi ≥4-point reduction total patients n = 1643 deucravacitinib n = 824 placebo n = 409 pasi 75, n/na (%) 553/664 (83.3)b 393/464 (84.7) 32/44 (72.7) spga 0/1, n/na (%) 496/601 (82.5)b 359/431 (83.3) 24/34 (70.6) athe denominator includes the patients who achieved clinical response and completed ≥1 dlqi item at baseline and ≥1 dlqi item at a post-baseline visit. btotal denominator includes patients who received apremilast. dlqi, dermatology life quality index; pasi 75, ≥75% improvement from baseline in psoriasis area and severity index score; spga 0/1, static physician’s global assessment score of 0 or 1. conclusions • psoriasis skin clearance, symptom reduction, and improved patient quality of life were correlated in the poetyk pso-1 and pso-2 trials — this correlation is consistent with that determined in other studies4-7 • higher clinical response was associated with greater pro measure response • pro measures capture patient-perceived treatment benefi ts that may not be ascertained by measuring rates of skin clearance with clinical assessments alone4 — psoriasis bears symptoms, such as pruritus, for which there are no validated objective measures,8 or which are best assessed by patients themselves9 in order to evaluate treatment effi cacy — among patients who achieved pasi 75 at week 16, 80.8% of patients who received deucravacitinib reported meaningful itch improvement on the pssd compared with 43.8% of patients who received placebo • among patients with and without clinical response, greater proportions of patients treated with deucravacitinib recorded improvement in their self-reported symptoms, signs, and quality of life compared with patients treated with placebo references 1. warren rb, et al. ann rheum dis. 2022;81:1570-1571. 2. papp ka, et al. [poster] presented at the 30th congress of the european academy of dermatology and venereology (eadv); september 29–october 2, 2021; virtual meeting. 3. augustin m, et al. [poster] presented at the american academy of dermatology (aad) annual meeting; march 25–29, 2022; boston, ma. 4. armstrong aw, et al. am j clin dermatol. 2019;20:155-164. 5. loft nd, et al. acta derm venereol. 2019;99:1224-1230. 6. schäfer i, et al. eur j dermatol. 2010;20:62-67. 7. thaçi d, et al. dermatol ther (heidelb). 2022;12:495-510. 8. price a, cohen de. dermatitis. 2014;225:334-344. 9. armstrong aw, et al. j dermatol treat. 2019;30:27-34. acknowledgments • this study was sponsored by bristol myers squibb • medical writing and editorial assistance was provided by eleanor bush, ma, of peloton advantage, llc, an open health company, and funded by bristol myers squibb disclosures • awa: grants and personal fees: abbvie, bristol myers squibb, eli lilly, janssen, leo pharma, and novartis; personal fees: boehringer ingelheim/parexel, celgene, dermavant, genentech, glaxosmithkline, menlo therapeutics, merck, modernizing medicine, ortho dermatologics, pfi zer, regeneron, sanofi genzyme, science 37, sun pharma, and valeant; grants: dermira, kyowa hakko kirin, and ucb, outside the submitted work • kap: speakers bureau: abbvie, amgen, astellas, celgene, eli lilly, galderma, janssen, kyowa hakko kirin, leo pharma, merck sharp & dohme, novartis, pfi zer, and valeant; grant/research support: abbvie, akros, allergan, amgen, anacor, arcutis, astrazeneca, baxalta, boehringer ingelheim, bristol myers squibb, celgene, coherus, dermira, dow pharma, eli lilly, galderma, genentech, glaxosmithkline, janssen, kyowa hakko kirin, leo pharma, medimmune, meiji seika pharma, merck serono, novartis, pfi zer, regeneron, roche, sanofi genzyme, takeda, ucb, and valeant; consultant: abbvie, akros, amgen, arcutis, astellas, astrazeneca, baxalta, baxter, boehringer ingelheim, bristol myers squibb, can-fite, celgene, coherus, dermira, dow pharma, eli lilly, forward pharma, galderma, genentech, janssen, kyowa hakko kirin, leo pharma, meiji seika pharma, merck serono, merck sharp & dohme, mitsubishi pharma, novartis, pfi zer, regeneron, roche, sanofi genzyme, takeda, ucb, and valeant; honoraria: abbvie, akros, amgen, baxter, boehringer ingelheim, celgene, coherus, eli lilly, forward pharma, galderma, glaxosmithkline, janssen, kyowa hakko kirin, merck sharp & dohme, merck serono, novartis, pfi zer, takeda, ucb, and valeant; scientifi c offi cer/steering committee/advisory board: abbvie, akros, amgen, anacor, astellas, baxter, boehringer ingelheim, bristol myers squibb, celgene, dow pharma, eli lilly, galderma, janssen, kyowa hakko kirin, merck serono, merck sharp & dohme, novartis, pfi zer, regeneron, sanofi genzyme, and valeant • jz, bb, yz, rmk, and sb: employees and shareholders of bristol myers squibb • jlb and md: employees of clinical outcomes solutions, which has received consulting fees from bristol myers squibb • bs: consultant (honoraria): abbvie, almirall, amgen, arcutis, arena, aristea, asana, boehringer ingelheim, bristol myers squibb, connect biopharma, dermavant, eli lilly, equillium, glaxosmithkline, immunic therapeutics, janssen, leo pharma, maruho, meiji seika pharma, mindera, novartis, ortho dermatologics, pfi zer, regeneron, sanofi genzyme, sun pharma, ucb, ventyx biosciences, and vtv therapeutics; speaker: abbvie, eli lilly, janssen, and sanofi genzyme; co-scientifi c director (consulting fee): corevitas’ (corrona) psoriasis registry; investigator: abbvie, cara, corevitas’ (corrona) psoriasis registry, dermavant, dermira, and novartis deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, in moderate to severe plaque psoriasis: correlations between patient-reported outcomes and clinical responses in the phase 3 clinical trials poetyk pso-1 and poetyk pso-2 april w. armstrong,1 kim a. papp,2 joe zhuo,3 brandon becker,3 yichen zhong,3 jennifer l. beaumont,4 michael derosa,4 renata m. kisa,3 subhashis banerjee,3 bruce strober5,6 1keck school of medicine, university of southern california, los angeles, ca; 2probity medical research, waterloo, ontario, canada; 3bristol myers squibb, princeton, nj; 4clinical outcomes solutions, chicago, il; 5yale university, new haven, ct; 6central connecticut dermatology, cromwell, ct presented at the fall clinical dermatology conference; october 20–23, 2022; las vegas, nv this poster may not be reproduced without written permission from the authors.email for april w. armstrong, md, mph: aprilarmstrong@post.harvard.edu scientifi c content on demand to request a copy of this poster: scan qr code via a barcode reader application qr codes are valid for 30 days after the congress presentation date. synopsis • in the phase 3 clinical trials poetyk pso-1 and pso-2, deucravacitinib was compared for effi cacy and safety with placebo and apremilast in the treatment of patients with moderate to severe plaque psoriasis1 — deucravacitinib is an oral, selective, allosteric tyrosine kinase 2 (tyk2) inhibitor approved by the us food and drug administration for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy — in each clinical trial, greater proportions of patients who received deucravacitinib achieved ≥75% reduction from baseline in the psoriasis area and severity index score (pasi 75)1 and static physician’s global assessment scores of 0 or 1 (spga 0/1),1 and showed meaningful improvements on psoriasis symptoms and signs diary (pssd) total scores (≥25 points)2 and dermatology life quality index (dlqi) total scores (≥4 points)3 compared with patients receiving placebo or apremilast • in this post hoc analysis of data pooled from both trials, clinical and patient-reported outcomes (pros) were found to be correlated • when analyzed by the deucravacitinib or placebo treatment arm, greater proportions of patients who received deucravacitinib reported symptom reduction and improved quality of life, both in patients who did and who did not achieve pasi 75 and spga 0/1 responses objective • to explore the correlations between responses on clinical and pro measures in pooled data from poetyk pso-1 and pso-2 methods • in poetyk pso-1 (n = 666) and pso-2 (n = 1020) adults (aged ≥18 years) with moderate to severe psoriasis were randomized 2:1:1 to deucravacitinib 6 mg once daily, placebo, or apremilast 30 mg twice daily — at week 16 in each trial, patients who received placebo crossed over to deucravacitinib • using data pooled from both trials, we evaluated the correlation between responses measured by pasi and spga on one hand, and the pro measures pssd (≥25 points)2 and dlqi (≥4 points)3 on the other — the analysis populations for the pssd and dlqi included all patients from the full analysis set who completed ≥1 item on the respective questionnaire at baseline and ≥1 post-baseline visit • at baseline, 1659 patients had a dlqi score recorded and 1553 had a pssd score recorded • spearman correlation coeffi cients between clinical and pro score changes from baseline to week 16 were calculated with all treatment groups combined • mean pssd and dlqi scores were determined within relative pasi and spga response levels • the proportions of patients achieving meaningful improvement (ie, response) in pssd total scores and on the dlqi were summarized by whether they did or did not achieve pasi 75 and spga 0/1, and were further analyzed by treatment arm — results are reported for patients receiving deucravacitinib or placebo outcome measures • pasi — clinician evaluated — range: 0–72, with higher scores indicating more severe disease • spga — clinician evaluated — range: 0 (clear) to 4 (severe) • pssd — patient rated — 5 skin symptoms (itch, tightness, burning, stinging, and pain) and 6 skin signs (dryness, cracking, scaling, shedding/fl aking, redness, and bleeding) associated with psoriasis were rated 0 (absent) to 10 (worst imaginable); averages within each domain were multiplied by 10, then averaged across both domains to obtain a total score — range: 0–100, with higher scores indicating heavier disease burden • dlqi — patient rated — 10 questions that assess the extent to which skin disease affects patients’ lives — range: 0–30, with higher scores indicating more severe impact of disease results correlations between clinical and pro measures • at week 16, change from baseline in relative pasi score was correlated with changes in the pssd total score (spearman’s rank correlation coeffi cient [r s ] = 0.536) and dlqi total score (r s = 0.421) in the total study population • at week 16, change from baseline in spga score was correlated with changes in the pssd total score (r s = 0.496) and dlqi total score (r s = 0.380) in the total study population • higher pasi or spga response was associated with greater pssd and dlqi responses at weeks 16, 24, and 52 in the total study population (figures 1–4) figure 1. pssd total score change from baseline by pasi response group (treatment arms and trials pooled, n = 1536) –50 –45 –40 –35 –30 –25 –20 –15 –10 –5 0 week 16 week 24 week 52 p ss d c h an ge f ro m b as e li n e a pasi <50 pasi 50–74 pasi 75–89 pasi 90–99 pasi 100 aat baseline, the mean pssd total score (sd) was 54.4 (23.30) in the deucravacitinib arm, 53.1 (23.09) in the placebo arm, and 55.7 (22.90) in the apremilast arm. pasi 50–100, 50%–100% improvement from baseline in the psoriasis area and severity index score; pssd, psoriasis symptoms and signs diary. figure 2. dlqi change from baseline by pasi response group (treatment arms and trials pooled, n = 1643) –14 –12 –10 –8 –6 –4 –2 0 week 16 week 24 week 52 d lq i ch an ge f ro m b as e li n e a pasi <50 pasi 50–74 pasi 75–89 pasi 90–99 pasi 100 athe mean baseline dlqi score (sd) among all patients in the study population was 12.0 (6.7). dlqi, dermatology life quality index; pasi 50–100, 50%–100% improvement from baseline psoriasis area and severity index score. figure 3. pssd change from baseline by spgaa change group (treatment arms and trials pooled, n = 1536) –50 –40 –30 –20 –10 0 10 20 week 16 week 24 week 52 p ss d c h an ge f ro m b as e li n e spga +1 spga 0 spga –1 spga –2 spga –3 or more aat baseline, 1345 patients in the total study population had an spga score of 3, and 340 had an spga score of 4. one patient had an spga score of 2; this patient was randomized but not treated. the mean baseline pssd total score (sd) was 54.4 (23.30) in the deucravacitinib arm, 53.1 (23.09) in the placebo arm, and 55.7 (22.90) in the apremilast arm. pssd, psoriasis symptoms and signs diary; spga, static physician’s global assessment. figure 4. dlqi change from baseline by spgaa change group (treatment arms and trials pooled, n = 1643) week 16 week 24 –12 –10 –8 –6 –4 –2 0 2 week 52 d lq i ch an ge f ro m b as e li n e spga +1 spga 0 spga –1 spga –2 spga –3 or more aat baseline, 1345 patients in the total study population had an spga score of 3 and 340 had an spga score of 4. one patient had an spga score of 2; this patient was randomized but not treated. the mean baseline dlqi score (sd) among all patients in the study population was 12.0 (6.7). dlqi, dermatology life quality index; spga, static physician’s global assessment. pssd response by clinical response • at week 16, pssd total score response (≥25-point reduction from baseline) was reported by 64.8% and 65.3% of all patients across both trials who achieved pasi 75 (356/549) and/or spga 0/1 (330/505), respectively (table 1) — greater proportions of patients who received deucravacitinib and achieved clinical response reported pssd total score response (68.6% of patients who achieved pasi 75 and 68.7% of patients who achieved spga 0/1) compared with patients who received placebo (31.3% of patients who achieved pasi 75 and 37.0% of patients who achieved spga 0/1) (table 1) — on the pssd itch item, meaningful improvement (≥2 points) was reported by 80.8% of patients receiving deucravacitinib who achieved pasi 75 and 80.1% of deucravacitinib-treated patients who achieved spga 0/1, compared with 43.8% of patients receiving placebo who achieved pasi 75 and 48.1% of placebo-treated patients who achieved spga 0/1 (figure 5) • at week 16, 27.9% and 29.8% of all patients across both trials who did not achieve pasi 75 (188/674) and/or did not achieve spga 0/1 (214/718), respectively, nonetheless reported pssd total score response — greater proportions of patients who received deucravacitinib and did not achieve clinical response nonetheless reported pssd total score response (41.8% of patients who did not achieve pasi 75 and 44.1% of patients who did not achieve spga 0/1) compared with patients who received placebo (10.4% of patients who did not achieve pasi 75 and 10.3% who did not achieve spga 0/1) — on the pssd itch item, meaningful improvement was reported by 54.9% of patients receiving deucravacitinib who did not achieve pasi 75 compared with 22.0% of patients receiving placebo who did not achieve pasi 75 table 1. pssd response at week 16 in patients who achieved clinical response pssd domain total patients n = 1536 deucravacitinib n = 765 placebo n = 383 total score (≥25-point reduction), n/na (%) pasi 75 356/549 (64.8)b 264/385 (68.6) 10/32 (31.3) spga 0/1 330/505 (65.3)b 248/361 (68.7) 10/27 (37.0) symptom score (≥25-point reduction), n/na (%) pasi 75 323/549 (58.8)b 240/385 (62.3) 10/32 (31.3) spga 0/1 296/505 (58.6)b 223/361 (61.8) 8/27 (29.6) sign score (≥25-point reduction), n/na (%) pasi 75 383/549 (69.8)b 284/385 (73.8) 10/32 (31.3) spga 0/1 354/505 (70.1)b 267/361 (74.0) 10/27 (37.0) athe denominator represents the patients who achieved clinical response and who completed ≥1 pssd item at baseline and ≥1 pssd item at a post-baseline visit. btotal denominator includes patients who received apremilast. pasi 75, ≥75% improvement from baseline in psoriasis area and severity index score; pssd, psoriasis symptoms and signs diary; spga 0/1, static physician’s global assessment score of 0 or 1. figure 5. pssd individual item response at week 16 in patientsa who achieved clinical response 0 10 20 30 40 50 60 70 80 90 deucravacitinib (n = 765) placebo (n = 383) p at ie n ts , % 80.8 80.1 79.7 80.3 63.6 63.2 58.7 58.4 66.2 66.2 85.7 84.8 72.7 72.9 84.2 84.5 85.7 85.3 79.2 78.9 49.9 48.2 43.8 48.1 46.9 40.7 37.5 37.0 31.3 25.9 34.4 29.6 43.8 48.1 46.9 48.1 46.9 51.9 43.8 48.1 37.5 48.1 31.3 33.3 pasi 75 spga 0/1 pasi 75 spga 0/1 pasi 75 spga 0/1 pasi 75 spga 0/1 pasi 75 spga 0/1 pasi 75 spga 0/1 pasi 75 spga 0/1 pasi 75 spga 0/1 pasi 75 spga 0/1 pasi 75 spga 0/1 pasi 75 spga 0/1 itch (≥2 points) tightness (≥2 points) burning (≥2 points) stinging (≥2 points) pain (≥2 points) dryness (≥2 points) cracking (≥2 points) scaling (≥2 points) shedding/flaking (≥2 points) redness (≥2 points) bleeding (≥2 points) adenominators include patients who achieved clinical response and completed ≥1 pssd item at baseline and ≥1 pssd item at a post-baseline visit. pasi 75, 75% reduction from baseline in psoriasis area and severity index score; pssd, psoriasis symptoms and signs diary; spga 0/1, static physician’s global assessment score of 0 or 1. dlqi response by clinical response • at week 16, dlqi response (≥4-point reduction from baseline) was reported by 83.3% and 82.5% of all patients across both trials who achieved pasi 75 (553/664) and/or spga 0/1 (496/601), respectively (table 2) — greater proportions of patients who received deucravacitinib and achieved clinical response reported meaningful dlqi improvement (84.7% of patients who achieved pasi 75 and 83.3% of patients who achieved spga 0/1) compared with patients who received placebo (72.7% of patients who achieved pasi 75 and 70.6% of patients who achieved spga 0/1) • at week 16, 54.7% and 57.3% of all patients across both trials who did not achieve pasi 75 (444/811) and/or did not achieve spga 0/1 (501/874), respectively, nonetheless reported dlqi response — greater proportions of patients who received deucravacitinib and did not achieve clinical response nonetheless reported meaningful dlqi improvement (67.1% of patients who did not achieve pasi 75 and 70.8% of patients who did not achieve spga 0/1) compared with patients who received placebo (40.5% of patients who did not achieve pasi 75 and 41.7% who did not achieve spga 0/1) table 2. dlqi response at week 16 in patients who achieved clinical response dlqi ≥4-point reduction total patients n = 1643 deucravacitinib n = 824 placebo n = 409 pasi 75, n/na (%) 553/664 (83.3)b 393/464 (84.7) 32/44 (72.7) spga 0/1, n/na (%) 496/601 (82.5)b 359/431 (83.3) 24/34 (70.6) athe denominator includes the patients who achieved clinical response and completed ≥1 dlqi item at baseline and ≥1 dlqi item at a post-baseline visit. btotal denominator includes patients who received apremilast. dlqi, dermatology life quality index; pasi 75, ≥75% improvement from baseline in psoriasis area and severity index score; spga 0/1, static physician’s global assessment score of 0 or 1. conclusions • psoriasis skin clearance, symptom reduction, and improved patient quality of life were correlated in the poetyk pso-1 and pso-2 trials — this correlation is consistent with that determined in other studies4-7 • higher clinical response was associated with greater pro measure response • pro measures capture patient-perceived treatment benefi ts that may not be ascertained by measuring rates of skin clearance with clinical assessments alone4 — psoriasis bears symptoms, such as pruritus, for which there are no validated objective measures,8 or which are best assessed by patients themselves9 in order to evaluate treatment effi cacy — among patients who achieved pasi 75 at week 16, 80.8% of patients who received deucravacitinib reported meaningful itch improvement on the pssd compared with 43.8% of patients who received placebo • among patients with and without clinical response, greater proportions of patients treated with deucravacitinib recorded improvement in their self-reported symptoms, signs, and quality of life compared with patients treated with placebo references 1. warren rb, et al. ann rheum dis. 2022;81:1570-1571. 2. papp ka, et al. [poster] presented at the 30th congress of the european academy of dermatology and venereology (eadv); september 29–october 2, 2021; virtual meeting. 3. augustin m, et al. [poster] presented at the american academy of dermatology (aad) annual meeting; march 25–29, 2022; boston, ma. 4. armstrong aw, et al. am j clin dermatol. 2019;20:155-164. 5. loft nd, et al. acta derm venereol. 2019;99:1224-1230. 6. schäfer i, et al. eur j dermatol. 2010;20:62-67. 7. thaçi d, et al. dermatol ther (heidelb). 2022;12:495-510. 8. price a, cohen de. dermatitis. 2014;225:334-344. 9. armstrong aw, et al. j dermatol treat. 2019;30:27-34. acknowledgments • this study was sponsored by bristol myers squibb • medical writing and editorial assistance was provided by eleanor bush, ma, of peloton advantage, llc, an open health company, and funded by bristol myers squibb disclosures • awa: grants and personal fees: abbvie, bristol myers squibb, eli lilly, janssen, leo pharma, and novartis; personal fees: boehringer ingelheim/parexel, celgene, dermavant, genentech, glaxosmithkline, menlo therapeutics, merck, modernizing medicine, ortho dermatologics, pfi zer, regeneron, sanofi genzyme, science 37, sun pharma, and valeant; grants: dermira, kyowa hakko kirin, and ucb, outside the submitted work • kap: speakers bureau: abbvie, amgen, astellas, celgene, eli lilly, galderma, janssen, kyowa hakko kirin, leo pharma, merck sharp & dohme, novartis, pfi zer, and valeant; grant/research support: abbvie, akros, allergan, amgen, anacor, arcutis, astrazeneca, baxalta, boehringer ingelheim, bristol myers squibb, celgene, coherus, dermira, dow pharma, eli lilly, galderma, genentech, glaxosmithkline, janssen, kyowa hakko kirin, leo pharma, medimmune, meiji seika pharma, merck serono, novartis, pfi zer, regeneron, roche, sanofi genzyme, takeda, ucb, and valeant; consultant: abbvie, akros, amgen, arcutis, astellas, astrazeneca, baxalta, baxter, boehringer ingelheim, bristol myers squibb, can-fite, celgene, coherus, dermira, dow pharma, eli lilly, forward pharma, galderma, genentech, janssen, kyowa hakko kirin, leo pharma, meiji seika pharma, merck serono, merck sharp & dohme, mitsubishi pharma, novartis, pfi zer, regeneron, roche, sanofi genzyme, takeda, ucb, and valeant; honoraria: abbvie, akros, amgen, baxter, boehringer ingelheim, celgene, coherus, eli lilly, forward pharma, galderma, glaxosmithkline, janssen, kyowa hakko kirin, merck sharp & dohme, merck serono, novartis, pfi zer, takeda, ucb, and valeant; scientifi c offi cer/steering committee/advisory board: abbvie, akros, amgen, anacor, astellas, baxter, boehringer ingelheim, bristol myers squibb, celgene, dow pharma, eli lilly, galderma, janssen, kyowa hakko kirin, merck serono, merck sharp & dohme, novartis, pfi zer, regeneron, sanofi genzyme, and valeant • jz, bb, yz, rmk, and sb: employees and shareholders of bristol myers squibb • jlb and md: employees of clinical outcomes solutions, which has received consulting fees from bristol myers squibb • bs: consultant (honoraria): abbvie, almirall, amgen, arcutis, arena, aristea, asana, boehringer ingelheim, bristol myers squibb, connect biopharma, dermavant, eli lilly, equillium, glaxosmithkline, immunic therapeutics, janssen, leo pharma, maruho, meiji seika pharma, mindera, novartis, ortho dermatologics, pfi zer, regeneron, sanofi genzyme, sun pharma, ucb, ventyx biosciences, and vtv therapeutics; speaker: abbvie, eli lilly, janssen, and sanofi genzyme; co-scientifi c director (consulting fee): corevitas’ (corrona) psoriasis registry; investigator: abbvie, cara, corevitas’ (corrona) psoriasis registry, dermavant, dermira, and novartis deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, in moderate to severe plaque psoriasis: correlations between patient-reported outcomes and clinical responses in the phase 3 clinical trials poetyk pso-1 and poetyk pso-2 april w. armstrong,1 kim a. papp,2 joe zhuo,3 brandon becker,3 yichen zhong,3 jennifer l. beaumont,4 michael derosa,4 renata m. kisa,3 subhashis banerjee,3 bruce strober5,6 1keck school of medicine, university of southern california, los angeles, ca; 2probity medical research, waterloo, ontario, canada; 3bristol myers squibb, princeton, nj; 4clinical outcomes solutions, chicago, il; 5yale university, new haven, ct; 6central connecticut dermatology, cromwell, ct presented at the fall clinical dermatology conference; october 20–23, 2022; las vegas, nv this poster may not be reproduced without written permission from the authors.email for april w. armstrong, md, mph: aprilarmstrong@post.harvard.edu scientifi c content on demand to request a copy of this poster: scan qr code via a barcode reader application qr codes are valid for 30 days after the congress presentation date. figure 1. percentage of pasi 75, pasi 90, and pasi 100 responders receiving continuous tildrakizumab 100 mg (left) and 200 mg (right) over time by baseline metabolic syndrome status in resurface 1 mets, metabolic syndrome; pasi, psoriasis area and severity index; til, tildrakizumab. • in resurface 2, the proportion of patients receiving tildrakizumab 100 mg who achieved pasi 75/90/100 were comparable between patients with vs without mets at week 52 and remained comparable at weeks 100 and 148 (figure 2) figure 2. percentage of pasi 75, pasi 90 and pasi 100 responders receiving continuous tildrakizumab 100 mg (left) and 200 mg (right) over time by baseline metabolic syndrome status in resurface 2 mets, metabolic syndrome; pasi, psoriasis area and severity index; til, tildrakizumab. • in patients receiving tildrakizumab 200 mg in resurface 2, those with mets had numerically lower pasi 75 response rates at week 100 and week 148 relative to patients without mets; pasi 90 and pasi 100 response rates at weeks 52, 100, and 148 were also lower in patients with mets vs without mets (figure 2) • at week 148, in both resurface 1 (figure 3) and resurface 2 (figure 4), overall pasi scores decreased from baseline — in resurface 1, the percentage decrease in median pasi scores in patients with vs without mets was 89% vs 92% (tildrakizumab 100 mg) and 88% vs 91% (tildrakizumab 200 mg), respectively — in resurface 2, the percentage decrease in median pasi scores in patients with vs without mets was 93% vs 96% (tildrakizumab 100 mg) and 84% vs 94% (tildrakizumab 200 mg), respectively figure 3. median absolute pasi scores over time in patients receiving a) tildrakizumab 100 mg and b) tildrakizumab 200 mg, stratified by metabolic syndrome status in resurface 1 a) b) mets, metabolic syndrome; pasi, psoriasis area and severity index; til, tildrakizumab. figure 4. median absolute pasi scores over time in patients receiving a) tildrakizumab 100 mg and b) tildrakizumab 200 mg, stratified by metabolic syndrome status in resurface 2 a) b) mets, metabolic syndrome; pasi, psoriasis area and severity index; til, tildrakizumab. conclusions • the efficacy of both tildrakizumab 100and 200-mg doses was maintained over 148 weeks of the resurface 1 and 2 studies without evidence of reduced drug survival in patients with mets and was comparable to that of patients without mets references 1) alberti kg, et al. circulation. 2009;120(16):1640–5. 2) fernandez-armenteros jm, et al. j eur acad dermatol venereol. 2019;33(1):128–35. 3) singh s, et al. plos one. 2017;12(7):e0181039. 4) langan sm, et al. j invest dermatol. 2012;132(3 pt 1):556–62. 5) talamonti m, et al. j eur acad dermatol venereol. 2018;32(10):1737–44. 6) jacobi a, et al. int j dermatol. 2016;55(3):296–302. 7) pinter a, et al. j dermatolog treat. 2019:1–7. 8) reich k, et al. lancet. 2017;390(10091):276–88. 9) national institutes of health. https:// www.nhlbi.nih.gov/files/docs/guidelines/atp3xsum.pdf; 2001 [accessed august 18, 2018]. 10) lebwohl m. presented at: aad annual meeting 2019. 11) leonardi c. presented at: aad annual meeting 2019. 12) mehta n, et al. j am acad dermatol. 2019;81(4 s1): ab131. acknowledgments we thank patients for their participation. the studies were funded by merck sharp & dohme corp., a subsidiary of merck & co., inc., kenilworth, nj, usa. analyses were funded by sun pharmaceutical industries, inc., princeton, nj, usa. editorial support was provided by puneet dang, phd, of alphabiocom, llc, and funded by sun pharmaceutical industries, inc. disclosures mgl is an employee of mount sinai, which receives research funds from abbvie, amgen, astrazeneca, boehringer ingelheim, celgene, eli lilly and co., incyte, janssen/ johnson & johnson, kadmon, leo pharmaceuticals, medimmune, novartis, pfizer, sciderm, ucb, ortho dermatologics, and vidac; and is a consultant for allergan, almirall, arcutis, avotres, birchbiomed, boehringer ingelheim, bristol-myers squibb, cara, castle biosciences, dermavant, encore, inozyme, leo pharmaceuticals, meiji, menlo, mitsubishi pharma, neuroderm, pfizer, promius/dr. reddy, theravance biopharma, and verrica. nnm is a full-time employee of the us government and has received support in the form of grants to the nih from abbvie, celgene, janssen, and novartis. abg has current consulting/advisory board agreements with abbvie; allergan; avotres therapeutics; beiersdorf; boehringer ingelheim; bristol-myers squibb; celgene; dermira; eli lilly and co.; incyte; janssen; leo pharmaceuticals; novartis; reddy labs; sun pharmaceutical industries, inc.; ucb; valeant; and xbiotech; and has received research/educational grants from boehringer ingelheim, incyte, janssen, novartis, ucb, and xbiotech. amm is an employee of sun pharmaceutical industries, inc.; and has individual shares in johnson & johnson, and as part of retirement account/mutual funds. jp is an employee of sun pharmaceutical industries, inc.; and has served as statistical consultant for sun pharmaceutical industries, inc.; and kyowa kirin pharmaceutical development. sjr is an employee of sun pharmaceutical industries, inc. mam has received grants and/or honoraria as a consultant, investigator, and/or speaker for abbvie, abbott labs, amgen, anacor, boehringer ingelheim, celgene, eli lilly and co., janssen, leo pharmaceuticals, merck, novartis, sienna, and ucb; and has been on an advisory board for abbvie, amgen, boehringer ingelheim, eli lilly and co., janssen, leo pharmaceuticals, and sienna. introduction • metabolic syndrome (mets) is a combination of common cardiometabolic abnormalities associated with an increased risk of cardiovascular disease and diabetes1 and has higher prevalence in patients with moderate to severe psoriasis compared with the overall population2-4 • in patients with psoriasis treated with anti-tumor necrosis factor or anti–interleukin (il)-17 agents, mets may reduce the absolute psoriasis area and severity index (pasi) response and long-term drug survival5-7 • tildrakizumab—a high-affinity, humanized, immunoglobulin g1κ, anti–il-23p19 monoclonal antibody—is approved in the us, europe, and australia for treatment of moderate to severe plaque psoriasis — the efficacy of tildrakizumab was demonstrated in 2 phase 3 clinical studies, resurface 1 (nct01722331) and resurface 2 (nct01729754)8 — treatment with tildrakizumab significantly increased the proportion of patients with ≥75%, ≥90%, and 100% improvement in pasi scores (pasi 75, pasi 90, and pasi 100, respectively) and physician’s global assessment 0/1 response rates compared with placebo8 • previously, we evaluated tildrakizumab efficacy in patients meeting national cholesterol education program-adult treatment panel iii (ncep-atp iii) criteria9 for mets (including diminished high-density lipoprotein cholesterol and elevated blood pressure, body mass index [bmi], triglycerides, and glucose) after 1 year of treatment — mets has a minimal effect on tildrakizumab efficacy10 and safety11 and there are no increases in cardiac events or worsening of diabetes in patients with mets following 1 year of tildrakizumab treatment12 objective • to update the efficacy of tildrakizumab in psoriasis patients with vs without mets with up to 3 years (148 weeks) of follow-up in resurface 1 and resurface 2 methods study design • this post hoc analysis of the resurface 1 and resurface 2 phase 3, double-blind, randomized controlled studies included patients aged ≥18 years with moderate to severe chronic plaque psoriasis; full trial designs were published previously8 • tildrakizumab 100 or 200 mg was administered at week 0, week 4, and every 12 weeks thereafter up to week 220/244 (resurface 1/2) — additional patients in resurface 2 received etanercept twice weekly to week 12 and once weekly to week 28 table 1. clinical definition of metabolic syndrome at baseline risk factor defining level bmia >30 kg/m2 triglycerides ≥150 mg/dl hdl cholesterol men women <40 mg/dl <50 mg/dl blood pressure ≥130/≥85 mm hg fasting glucose ≥110 mg/dl adiagnosis of metabolic syndrome was made when ≥3 risk factors were present. bmi was used as a surrogate for waist circumference. bmi, body mass index; hdl, high-density lipoprotein. evaluations and assessments • at baseline, metabolic syndrome was defined as the presence of ≥3 risk factors per the ncep-atp iii criteria (table 1)9 • data were collected from patients who continuously received tildrakizumab 100 or 200 mg • efficacy of tildrakizumab, stratified by mets status, was determined by the proportion of patients achieving pasi 75/90/100 in each visit, and absolute and percent changes in median pasi scores from baseline to week 148 • missing data were imputed as nonresponse for pasi response rates and using last observation carried forward methodology for pasi scores tildrakizumab efficacy by metabolic syndrome status in psoriasis: post hoc analysis of 3-year data from the phase 3 resurface 1 and resurface 2 studies mark g lebwohl,1 nehal n mehta,2 alice b gottlieb,3 alan m mendelsohn,4 jeff parno,4 stephen j rozzo,4 m alan menter5 1department of dermatology, mount sinai hospital, new york, ny, usa; 2national heart, lung and blood institute, national institutes of health, bethesda, md, usa; 3department of dermatology, icahn school of medicine at mount sinai, new york, ny, usa; 4sun pharmaceutical industries, inc., princeton, nj, usa; 5division of dermatology, baylor scott & white, and texas a&m college of medicine, dallas, tx, usa results • of patients who continuously received tildrakizumab 100 (n = 124) and 200 mg (n = 147), 26 (21%) and 34 (23%), respectively had mets in resurface 1 • in resurface 2, 44 (21%) and 30 (19%) patients continuously receiving tildrakizumab 100 (n = 214) and 200 mg (n = 160), respectively, had mets • baseline demographic and disease characteristics were similar between groups; patients with mets had numerically higher mean baseline weight, bmi, and prevalence of cardiovascular disease and diabetes mellitus vs patients with no mets (table 2) table 2. patient demographics and disease characteristics by trial, treatment group and metabolic syndrome status resurface 1 resurface 2 til 100 mg til 200 mg til 100 mg til 200 mg without mets (n = 98) with mets (n = 26) without mets (n = 113) with mets (n = 34) without mets (n = 170) with mets (n = 44) without mets (n = 130) with mets (n = 30) age, y 46.1 ± 14.0 49.1 ± 12.7 46.2 ± 13.5 50.7 ± 11.0 43.2 ± 13.2 45.9 ± 12.7 44.6 ± 13.2 48.7 ± 12.4 sex, male, n (%) 65 (66.3) 18 (69.2) 80 (70.8) 19 (55.9) 120 (70.6) 34 (77.3) 82 (63.1) 23 (76.7) race, white, n (%) 64 (65.3) 21 (80.8) 67 (59.3) 27 (79.4) 156 (91.8) 41 (93.2) 118 (90.8) 29 (96.7) weight at baseline, kg 80.8 ± 18.1 106.0 ± 29.6 81.7 ± 17.5 112.0 ± 32.2 82.6 ± 17.0 106.9 ± 21.7 82.0 ± 17.8 108.2 ± 17.6 bmi, kg/m2 27.9 ± 6.0 35.6 ± 8.5 28.3 ± 5.8 38.5 ± 8.3 27.5 ± 5.3a 35.6 ± 6.1 27.3 ± 5.3 37.6 ± 9.8 body surface area, % 29.4 ± 16.7 32.2 ± 16.6 32.6 ± 19.5 30.1 ± 19.4 34.1 ± 18.4 30.3 ± 18.9 31.4 ± 17.2 27.6 ± 12.9 disease duration, y 17.2 ± 12.6 16.2 ± 12.3 16.6 ± 11.5 16.7 ± 12.9 16.1 ± 10.6 15.2 ± 11.2 18.0 ± 13.5 20.1 ± 14.8 baseline pasi score 19.9 ± 7.1 20.5 ± 7.1 21.5 ± 9.3 20.6 ± 9.7 19.6 ± 6.9 20.8 ± 8.8 19.5 ± 7.2 19.2 ± 6.3 baseline pga score 3.3 ± 0.6 3.4 ± 0.6 3.4 ± 0.6 3.5 ± 0.6 3.3 ± 0.5 3.4 ± 0.6 3.3 ± 0.6b 3.4 ± 0.6 cv disorders, n (%) 14 (14.3) 17 (65.4) 31 (27.4) 16 (47.1) 29 (17.1) 17 (38.6) 27 (20.8) 16 (53.3) diabetes, n (%) 8 (8.2) 8 (30.8) 11 (9.7) 8 (23.5) 5 (2.9) 7 (15.9) 11 (8.5) 7 (23.3) psoriatic arthritis, n (%) 16 (16.3) 5 (19.2) 19 (16.8) 9 (26.5) 24 (14.1) 11 (25.0) 17 (13.1) 4 (13.3) response to >1 traditional systemic medicine, n (%)c 22 (44.9) 5 (71.4) 40 (65.6) 8 (57.1) 111 (65.3) 24 (54.6) 80 (61.5) 17 (56.7) prior exposure to biologic therapy for psoriasis, n (%) 16 (16.3) 8 (30.8) 20 (17.7) 7 (20.6) 23 (13.5) 5 (11.4) 17 (13.1) 7 (23.3) data provided as mean ± standard deviation unless otherwise indicated. an = 169; bn = 129; cdata not available for the missing patients in each group. bmi, body mass index; cv, cardiovascular; mets, metabolic syndrome; pasi, psoriasis area and severity index; pga, physician’s global assessment; til, tildrakizumab. • in resurface 1, a total of 2 patients with mets (both receiving tildrakizumab 100 mg [7.7%]) and 17 patients without mets (n = 11 [11.2%] receiving tildrakizumab 100 mg and n = 6 [5.4%] receiving tildrakizumab 200 mg) did not complete the study through week 148 • in resurface 2, 12 patients with mets (n = 7 [15.9%] receiving tildrakizumab 100 and n = 5 [16.6%] receiving tildrakizumab 200 mg) and 37 patients without mets (n = 21 [12.6%] receiving tildrakizumab 100 mg and n = 16 [12.4%] receiving tildrakizumab 200 mg) did not complete the study through week 148 — the most frequent reason for discontinuation was withdrawal by patient — two patients with mets receiving tildrakizumab 200 mg withdrew due to an adverse event in resurface 2 • in resurface 1, the proportion of patients receiving tildrakizumab 100 mg and 200 mg who achieved pasi 75/90/100 were comparable between patients with vs without mets at week 52 and remained comparable at weeks 100 and 148 (figure 1) week without mets (n = 170) with mets (n = 44) 4 8 12 16 22 28 32 36 40 46 52 60 64 76 88 100 112 124 136 1480 0 5 10 15 20 25 pa s i, m ed ia n (q 1, q 3) til 100 mg 0 5 10 15 20 25 pa s i, m ed ia n (q 1, q 3) til 200 mg week without mets (n = 130) with mets (n = 30) 4 8 12 16 22 28 32 36 40 46 52 60 64 76 88 100 112 124 136 1480 week with mets (n = 26)without mets (n = 98) 4 8 12 16 22 28 32 36 40 46 52 60 64 76 88 100 112 124 136 1480 0 5 10 15 20 25 pa s i, m ed ia n (q 1, q 3) til 100 mg week without mets (n = 113) with mets (n = 34) 4 8 12 16 22 28 32 36 40 46 52 60 64 76 88 100 112 124 136 1480 0 5 10 15 20 25 pa s i, m ed ia n (q 1, q 3) til 200 mg 0 20 40 60 80 100 week p a s i 7 5 r e s p on de rs ,% 4 8 12 16 22 28 32 36 40 46 52 60 64 76 88 100 112 124 136 148 86% 85% 76% 65% 71% 69% 0 20 40 60 80 100 week p a s i 7 5 r e s p on de rs ,% 4 8 12 16 22 28 32 36 40 46 52 60 64 76 88 100 112 124 136 148 76% 76% 81% 68% 74% 71% 0 20 40 60 80 100 week p a s i9 0 r e s p on de rs ,% 4 8 12 16 22 28 32 36 40 46 52 60 64 76 88 100 112 124 136 148 62% 50% 50% 38% 51% 42% 0 20 40 60 80 100 week p a s i 9 0 r e s p on de rs ,% 4 8 12 16 22 28 32 36 40 46 52 60 64 76 88 100 112 124 136 148 55% 47% 59% 41% 55% 47% 0 20 40 60 80 100 week p a s i 1 00 r e s p on de rs ,% without mets (n = 98) with mets (n = 26) 4 8 12 16 22 28 32 36 40 46 52 60 64 76 88 100 112 124 136 148 31% 31% 22% 27% 23% 27% 0 20 40 60 80 100 week p a s i1 00 r e s p on de rs ,% without mets (n = 113) with mets (n = 34) 4 8 12 16 22 28 32 36 40 46 52 60 64 76 88 100 112 124 136 148 35% 21% 31% 21% 27% 24% til 100 mg til 200 mg pasi 75 pasi 90 pasi 100 0 20 40 60 80 100 week p a s i 7 5 r e s p on de rs , % 4 8 12 16 22 28 32 36 40 46 52 60 64 76 88 100 112 124 136 148 86% 85% 76% 65% 71% 69% 0 20 40 60 80 100 week p a s i 7 5 r e s p on de rs ,% 4 8 12 16 22 28 32 36 40 46 52 60 64 76 88 100 112 124 136 148 76% 76% 81% 68% 74% 71% 0 20 40 60 80 100 week p a s i9 0 r e s p on de rs ,% 4 8 12 16 22 28 32 36 40 46 52 60 64 76 88 100 112 124 136 148 62% 50% 50% 38% 51% 42% 0 20 40 60 80 100 week p a s i 9 0 r e s p on de rs ,% 4 8 12 16 22 28 32 36 40 46 52 60 64 76 88 100 112 124 136 148 55% 47% 59% 41% 55% 47% 0 20 40 60 80 100 week p a s i 1 00 r e s p on de rs ,% without mets (n = 98) with mets (n = 26) 4 8 12 16 22 28 32 36 40 46 52 60 64 76 88 100 112 124 136 148 31% 31% 22% 27% 23% 27% 0 20 40 60 80 100 week p a s i1 00 r e s p on de rs ,% without mets (n = 113) with mets (n = 34) 4 8 12 16 22 28 32 36 40 46 52 60 64 76 88 100 112 124 136 148 35% 21% 31% 21% 27% 24% til 100 mg til 200 mg pasi 75 pasi 90 pasi 100 0 20 40 60 80 100 week p a s i 7 5 r e s p on de rs , % 4 8 12 16 22 28 32 36 40 46 52 60 64 76 88 100 112 124 136 148 94% 86% 88% 77% 79% 73% 0 20 40 60 80 100 week p a s i 7 5 r e s p on de rs , % 4 8 12 16 22 28 32 36 40 46 52 60 64 76 88 100 112 124 136 148 87% 87% 85% 73% 81% 63% 0 20 40 60 80 100 week p a s i9 0 r e s p on de rs ,% 4 8 12 16 22 28 32 36 40 46 52 60 64 76 88 100 112 124 136 148 79% 68% 66% 52% 60% 57% 0 20 40 60 80 100 week p a s i 9 0 r e s p on de rs ,% 4 8 12 16 22 28 32 36 40 46 52 60 64 76 88 100 112 124 136 148 66% 53% 68% 53% 58% 43% 0 20 40 60 80 100 week p a s i 1 00 r e s p on d er s , % without mets (n = 170) with mets (n = 44) 4 8 12 16 22 28 32 36 40 46 52 60 64 76 88 100 112 124 136 148 38% 32% 29% 30% 32% 34% 0 20 40 60 80 100 week p a s i 1 00 r e s p on d er s , % without mets (n = 130) with mets (n = 30) 4 8 12 16 22 28 32 36 40 46 52 60 64 76 88 100 112 124 136 148 36% 23% 38% 20% 32% 23% til 100 mg til 200 mg pasi 75 pasi 90 pasi 100 0 20 40 60 80 100 week p a s i 7 5 r e s p on de rs , % 4 8 12 16 22 28 32 36 40 46 52 60 64 76 88 100 112 124 136 148 94% 86% 88% 77% 79% 73% 0 20 40 60 80 100 week p a s i 7 5 r e s p on de rs , % 4 8 12 16 22 28 32 36 40 46 52 60 64 76 88 100 112 124 136 148 87% 87% 85% 73% 81% 63% 0 20 40 60 80 100 week p a s i9 0 r e s p on de rs ,% 4 8 12 16 22 28 32 36 40 46 52 60 64 76 88 100 112 124 136 148 79% 68% 66% 52% 60% 57% 0 20 40 60 80 100 week p a s i 9 0 r e s p on de rs ,% 4 8 12 16 22 28 32 36 40 46 52 60 64 76 88 100 112 124 136 148 66% 53% 68% 53% 58% 43% 0 20 40 60 80 100 week p a s i 1 00 r e s p on d er s , % without mets (n = 170) with mets (n = 44) 4 8 12 16 22 28 32 36 40 46 52 60 64 76 88 100 112 124 136 148 38% 32% 29% 30% 32% 34% 0 20 40 60 80 100 week p a s i 1 00 r e s p on d er s , % without mets (n = 130) with mets (n = 30) 4 8 12 16 22 28 32 36 40 46 52 60 64 76 88 100 112 124 136 148 36% 23% 38% 20% 32% 23% til 100 mg til 200 mg pasi 75 pasi 90 pasi 100 presented at fall clinical dermatology conference for pas & nps 2020, april 3–5, orlando, fl, usa synopsis • prior biologic treatment can impact responses to biologics in patients with moderate to severe plaque psoriasis.1 objectives to assess clinical and health-related quality of life (hrqol) outcomes in bimekizumab (bkz)-treated patients without prior biologic treatment (biologic-naïve) vs those with prior biologic treatment (biologic-experienced). methods • data were pooled from the be sure, be vivid, be ready, and be radiant phase 3/3b trials for patients with moderate to severe plaque psoriasis; full study designs have been published previously.2–5 • patients included in these analyses were randomized at baseline to bkz 320 mg every 4 weeks (q4w), then received bkz 320 mg q4w or q8w maintenance dosing from week 16 for the remainder of the double-blinded trials. in this analysis, q4w and q8w treatment groups were combined (bkz total). • patients with previous primary failure (no response within 12 weeks) to either ≥1 anti-interleukin (il)-17 or >1 other biologic treatment were excluded from all trials. • we report ≥90% improvement from baseline in psoriasis area and severity index (pasi 90), complete skin clearance (pasi 100), and dermatology life quality index (dlqi) 0/1, indicating no effect of skin disease on a patient’s life, through one year in patients who had received 0, 1, 2, or ≥3 prior biologics. • we also report responses by type of prior biologic: anti-il-17, anti-tumor necrosis factor (tnf), anti-il-12/23, and anti-il-23. • missing data were handled using non-responder imputation (nri). results • 1,186 patients randomized to bkz continued to the maintenance periods of the trials and received bkz 320 mg q4w or q8w (bkz total); 745 were biologic-naïve, whilst 314, 98, and 29 had received 1, 2, or ≥3 prior biologics, respectively (figure 1). • baseline characteristics were similar in biologic-naïve and biologic-experienced patients, with the exception of duration of psoriasis which was higher in biologic-experienced patients (table 1). • at week 16 and week 48, pasi 90 (figure 2a), pasi 100 (figure 3a), and dlqi 0/1 (figure 4a) responses were consistently high in biologic-naïve patients, as well as in those who had received 1 or 2 prior biologics. • responses were numerically lower in the subgroup of patients who had received ≥3 prior biologics (figure 2a–4a). • in biologic-experienced patients, high levels of pasi 90, pasi 100, and dlqi 0/1 responses were observed across all subgroups by type of prior biologic (figure 2b–4b). summary conclusion high levels of skin clearance and hrqol benefit were observed with bkz in biologic-naïve patients, and in those who had received 1 or 2 prior biologics. those who had received ≥3 prior biologics experienced lower responses, however, these data should be interpreted with caution due to the small number of patients in this subgroup. in biologic-experienced patients, responses were generally consistent regardless of type of prior biologic used. mark lebwohl,1 april armstrong,2 joseph f. merola,3 alice b. gottlieb,1 leah davis,4 braulio gomez,5 susanne wiegratz,6 nancy cross,4 bruce strober7,8 bimekizumab efficacy through one year in patients with moderate to severe plaque psoriasis in subgroups defined by prior biologic treatment: pooled results from four phase 3/3b trials bkz: bimekizumab; bsa: body surface area; dlqi: dermatology life quality index; hrqol: health-related quality of life; iga: investigator’s global assessment; il: interleukin; nri: non-responder imputation; pasi 90/100: ≥90%/100% improvement from baseline in the psoriasis area and severity index; q4w: every 4 weeks; q8w: every 8 weeks; sd: standard deviation; tnf: tumor necrosis factor. institutions: 1dept. of dermatology, icahn school of medicine at mount sinai, new york, ny, usa; 2keck school of medicine of usc, dermatology, los angeles, ca, usa; 3harvard medical school, brigham and women’s hospital, boston, ma, usa; 4ucb pharma, morrisville, nc, usa; 5ucb pharma, smyrna, ga, usa; 6ucb pharma, monheim, germany; 7yale university, school of medicine new haven, ct, usa; 8central connecticut dermatology research, cromwell, ct, usa. references: 1wade r et al. systematic reviews 2020; 9:132; 2warren rb et al. n engl j med 2021;385:130–141, nct03412747; 3reich k et al. lancet 2021;397:487–498, nct03370133; 4gordon kb et al. lancet 2021;397:475–486, nct03410992; 5reich k et al. n engl j med 2021;385:142–152, nct03536884. author contributions: substantial contributions to study conception/design, or acquisition/analysis/interpretation of data: ml, aa, jfm, abg, ld, bg, sw, nc, bs; drafting of the publication, or revising it critically for important intellectual content: ml, aa, jfm, abg, ld, bg, sw, nc, bs; final approval of the publication: ml, aa, jfm, abg, ld, bg, sw, nc, bs. disclosures: ml: employee of mount sinai and receives research funds from abbvie, amgen, arcutis, avotres, boehringer ingelheim, dermavant, eli lilly, incyte, janssen research & development, llc, ortho dermatologics, regeneron, and ucb pharma; consultant for aditum bio, almirall, altrubio inc., anaptysbio, arcutis, aristea therapeutics, arrive technologies, avotres therapeutics, biomx, boehringer ingelheim, bristol myers squibb, cara therapeutics, castle biosciences, corrona, dermavant, dr. reddy’s laboratories, evelo biosciences, evommune, inc., facilitatation of international dermatology education, forte biosciences, foundation for research and education in dermatology, helsinn therapeutics, hexima ltd., leo pharma, meiji seika pharma, mindera, pfizer, seanergy, and verrica. aa: research investigator and/or scientific advisor to abbvie, almirall, arcutis, aslan, boehringer ingelheim, bristol myers squibb, dermavant, dermira, eli lilly, epi, incyte, janssen, leo pharma, nimbus, novartis, ortho dermatologics, pfizer, regeneron, sun pharma, sanofi, and ucb pharma. jfm: consultant and/or investigator for abbvie, amgen, biogen, bristol myers squibb, dermavant, eli lilly, janssen, leo pharma, pfizer, novartis, regeneron, sanofi, sun pharma, and ucb pharma. abg: honoraria as an advisory board member, non-promotional speaker, or consultant for amgen, anaptysbio, avotres therapeutics, boehringer ingelheim, bristol myers squibb, dermavant, eli lilly, janssen, novartis, pfizer, sanofi, sun pharma, ucb pharma, and xbiotech (stock options for an ra project); research/educational grants from anaptysbio, bristol myers squibb, janssen, novartis, ortho dermatologics, sun pharma, and ucb pharma; all funds go to the icahn school of medicine at mount sinai. ld, bg, sw, nc: employees and shareholders of ucb pharma. bs: consultant (honoraria) for abbvie, almirall, amgen, arcutis, arena, aristea, asana, boehringer ingelheim, bristol myers squibb, connect biopharma, dermavant, eli lilly, epi health, evelo biosciences, immunic therapeutics, janssen, leo pharma, maruho, meiji seika pharma, mindera health, novartis, ono, pfizer, regeneron, sanofi genzyme, sun pharma, ucb pharma, union therapeutics, ventyxbio, and vtv therapeutics; stock options for connect biopharma and mindera health; speaker for abbvie, eli lilly, janssen, regeneron, and sanofi genzyme; scientific co-director (consulting fee) for corevitas (formerly corrona) psoriasis registry; investigator for abbvie, cara, corevitas psoriasis registry, dermavant, dermira, and novartis; editor-in-chief (honorarium) for the journal of psoriasis and psoriatic arthritis. acknowledgements: these studies were funded by ucb pharma. we thank the patients and their caregivers in addition to the investigators and their teams who contributed to these studies. the authors acknowledge yasha najafi, msc, costello medical, london, uk, for medical writing and editorial assistance and the design team, costello medical, uk for graphic design assistance. all costs associated with development of this poster were funded by ucb pharma. biologic-naïve (n=745) biologic-experienced (n=441) age (years), mean ± sd 43.7 ± 13.7 47.9 ± 13.6 male, n (%) 514 (69.0) 312 (70.7) caucasian, n (%) 634 (85.1) 400 (90.7) weight (kg), mean ± sd 89.6 ± 22.0 89.2 ± 21.8 duration of psoriasis (years), mean ± sd 15.7 ± 11.8 22.5 ± 12.8 pasi, mean ± sd 20.5 ± 7.5 21.4 ± 7.6 bsa (%), mean ± sd 25.8 ± 15.3 27.3 ± 16.3 iga,a n (%) 3: moderate 502 (67.4) 276 (62.6) 4: severe 241 (32.3) 164 (37.2) dlqi, mean ± sd 10.1 ± 6.1 11.3 ± 6.9 data are reported for those patients who had not previously received biologic treatment (biologic-naïve) and those who had previously received ≥1 biologic treatment (biologic-experienced) prior to enrolling in the trials. an=2 biologic-naïve and n=1 biologic-experienced patients had baseline iga of 2 (mild). all studies included q4w dosing from week 0–16; be sure, be ready, and be radiant also included q8w maintenance dosing to the end of the trial. included patients received bkz during the initial 16-week period, and during the maintenance period. apasi outcomes are reported through week 48 in all included trials; dlqi is reported to week 48 in be sure, be ready, and be radiant, and week 52 in be vivid, due to differences in scheduling of dlqi assessments. high levels of skin clearance were observed with bimekizumab in patients who had recieved 0, 1, or 2 prior biologics, regardless of prior biologic used 71.3% 0 prior biologics 1 prior biologic 2 prior biologics ≥3 prior biologics week 48 pasi 100 response: data were pooled from the be sure, be vivid, be ready, and be radiant phase 3/3b trials: type of prior biologic 0 prior biologics 1 prior biologic 2 prior biologics ≥3 prior biologics n=745 n=314 n=98 n=29 74.2% 69.4% 44.8% n=236 n=179n=66 n=64 anti-il-17 anti-tnfanti-il-12/23 anti-il-23 figure 4 dlqi 0/1 response rates at week 16 and week 48/52 (nri) figure 3 pasi 100 response rates through week 48 (nri) figure 2 pasi 90 response rates through week 48 (nri) table 1 baseline characteristics figure 1 study design: included patients by number of prior biologics week 48 was the last common timepoint across the included studies; be sure and be ready ran for 56 weeks, be vivid ran for 52 weeks, and be radiant ran for 48 weeks; to pool data across all four studies, data from weeks 52–56 were not included. week 48 was the last common timepoint across the included studies; be sure and be ready ran for 56 weeks, be vivid ran for 52 weeks, and be radiant ran for 48 weeks; to pool data across all four studies, data from weeks 52–56 were not included. due to differences in scheduling of dlqi assessments in the trials, common visits at week 16 (all trials), and week 48 (be sure, be ready, and be radiant) and week 52 (be vivid) are shown. week 16week 0 week 48/52a received ≥1 bkz dose at week 16 or later randomized to bkz bkz 320 mg q4w bkz 320 mg q4w or q8w biologic-naïve (n=745) biologic-experienced (n=441) biologic-naïve (n=857) biologic-experienced (n=505) be sure2 be vivid3 be ready4 be radiant5 84.9% b) pasi 90 response by type of prior biologic p ro p o rt io n o f p a ti e n ts w it h p a s i 9 0 r e sp o n se ( % ) week 0 2820161282 40 48 80 60 40 20 0 100 443632244 86.9% 81.8% 84.4% 92.2% 92.4% 90.9% 82.8% anti-tnf (n=179) anti-il-12/23 (n=66) anti-il-17 (n=236) anti-il-23 (n=64) 88.2% a) pasi 90 response by number of prior biologics p ro p o rt io n o f p a ti e n ts w it h p a s i 9 0 r e sp o n se ( % ) week 0 2820161282 40 48 80 60 40 20 0 100 443632244 86.8% 84.7% 69.0% 82.8% 92.9% 91.1% 90.5% 2 prior biologics (n=98) 1 prior biologic (n=314) 0 prior biologics (n=745) ≥3 prior biologics (n=29) 66.5% p ro p o rt io n o f p a ti e n ts w it h p a s i 1 0 0 r e sp o n se ( % ) week 0 2820161282 40 48 80 60 40 20 0 100 443632244 72.5% 63.6% 71.9% b) pasi 100 response by type of prior biologic 68.2% 65.4% 65.6% 60.6% anti-tnf (n=179) anti-il-12/23 (n=66) anti-il-17 (n=236) anti-il-23 (n=64) 74.2% p ro p o rt io n o f p a ti e n ts w it h p a s i 1 0 0 r e sp o n se ( % ) week 0 2820161282 40 48 80 60 40 20 0 100 443632244 71.3% 69.4% 44.8% a) pasi 100 response by number of prior biologics 2 prior biologics (n=98) 1 prior biologic (n=314) 0 prior biologics (n=745) ≥3 prior biologics (n=29) 44.8% 74.5% 65.9% 63.9% p ro p o rt io n o f p a ti e n ts w it h d l q i 0 /1 r e sp o n se ( % ) week 16 80 60 40 20 0 100 anti-il-17 (n=236) anti-tnf (n=179) anti-il-12/23 (n=66) anti-il-23 (n=64) b) dlqi 0/1 response by type of prior biologic week 48/52 75.0% 78.8%78.8% 78.8%73.2% 60.9% 80.4% 75.0% p ro p o rt io n o f p a ti e n ts w it h d l q i 0 /1 r e sp o n se ( % ) week 16 80 60 40 20 0 100 2 prior biologics (n=98) 1 prior biologic (n=314) 0 prior biologics (n=745) ≥3 prior biologics (n=29) a) dlqi 0/1 response by number of prior biologics week 48/52 74.0% 77.6%72.0% 80.3%79.6% 65.5% 82.7% 65.5% to receive a copy of this poster, scan the qr code or visit the website below. website: ucbposters.com/fc2022; poster id: 2 link expiration: 21 january 2023 presented at the 42nd annual fall clinical dermatology conference | las vegas, nv | october 20th–23rd, 2022 skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 238 original research enhancing patient compliance for usage of laundry detergents free of dyes and perfumes: potential impact of better cleaning performance mary b. johnson1, c. elaine cella1, amanda pessler1, dan b. dillard1, andy sullivan1 1the procter & gamble company, cincinnati, oh laundry detergent formulations and sensitive skin sensitive skin is often identified through unpleasant sensory reactions to consumer products such as cosmetics, soaps, toiletries, and laundry detergents after contact with the skin.1 epidemiological studies highlight the increasing prevalence of sensitive skin. recent surveys demonstrate the prevalence of sensitive skin, with 44.6% of respondents reporting “sensitive” or “very sensitive” skin.2 some investigations report 69% of women in the united states as having sensitive skin.3 despite a lack of robust diagnostic tests, sensitive skin is largely recognized as a genuine dermatological condition. background sensitive skin, an often self-reported condition, is characterized by an unpleasant sensory experience to a variety of consumer products. certain ingredients in consumer products, such fragrances and dyes, are believed to exacerbate skin sensitivities. due to an increased prevalence of people reporting sensitive skin, a variety of consumer products are formulated for people with this condition. a segment of commercially marketed laundry detergents, commonly known as free detergents, have been formulated without dyes and perfumes to accommodate skin sensitivities. in the us and canada respectively, 80% and 97% of dermatologist recommend the use of free detergents for their patients with sensitive skin. however, consumers have expressed dissatisfaction with free detergents, with 39% reporting they are not satisfied with their free detergent’s cleaning performance. when people switch from the leading free laundry detergent, they will switch to a non-free detergent 60% of the time, going against dermatologist recommendations and potentially further aggravating their skin sensitivities. a survey of us households with sensitive skin showed that 98.8% said that they would be more likely to consistently use a detergent that cleans better. herein are reported data showing tide pods free & gentle outperformed other free detergents in cleaning across a wide variety of laundry stains and in sem visual analysis of soil residues on fibers. it is postulated that the better cleaning detergent may help drive patient compliance with dermatologist recommendations for usage of a free detergent for their patients with sensitive skin. abstract skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 239 ingredients such as dyes and perfumes are frequently reported triggers of sensitive skin. some dyes and perfumes have been shown to be skin sensitizers, capable of eliciting a response in skin over time.4 clinical studies have suggested that residual detergent on clothing can react with skin on an irritant basis.5 several commercially available laundry detergents designed for sensitive skin are formulated without fragrances and dyes; these detergents are typically referred to as “free detergents”. while laundry detergents have been associated with sensitive skin, there is no present link between laundry detergents and other skin conditions such as atopic dermatitis.6 because it is believed that certain ingredients in traditional detergent formulations can aggravate sensitive skin, 80% and 97% of dermatologist in the us and canada respectively, recommend the use of free detergents for their patients with sensitive skin.7 in addition to formulating free detergents without fragrances and dyes, other ingredients are carefully screened so that detergents can remain mild on skin while providing cleaning performance. surfactants are major components of detergents and highly effective in removing dirt and soils in laundry. the chemical properties of different surfactants play a role in their cleaning performance and their skin irritation potential.8,9 surfactants can bind to keratin on the skin, causing protein denaturation. this leads to damage of the cell membrane, causing adverse skin responses such as redness, itchiness and irritation.10 advanced detergent formulation with different surfactants can impart significant cleaning performance while remaining mild on skin.11 for further cleaning performance, enzymes are added to laundry detergents to assist in breaking down the chemical bonds of stains and odor-causing molecules. enzymes will speed up the natural process of stain decomposition, particularly with biological contaminants.12 enzyme-containing laundry products have an extensive history of safe use, and recent studies have determined that concentrations of enzymes in detergents do not cause adverse skin events.13 special consideration is taken when formulating laundry detergents to ensure they are gentle on skin; detergents that clean well are sometimes perceived to be harsh on skin. to confirm their mildness on skin, detergents are evaluated for their potential to cause skin irritation through human in vivo patch testing. in vivo patch testing methodologies include human repeat insult patch tests (hript) and cumulative irritation testing (cit). these tests have been referred to as the “gold standard” for irritancy testing and represent the most common exposure of patients to detergent residues, which is washed fabrics in prolonged contact with human skin.14 hripts have been used to evaluate irritancy potential for over 50 years and have been called the most reliable test methods by which confirmatory human data can be made available.15 these testing methodologies represent an investigation whose outcome is compared with that of historical controls, providing results that can be interpreted using the scientific method.16,17 as such, dermatological associations, including the national eczema association, request patch testing data when evaluating consumer products for their seal of approval. in vivo testing protocols have demonstrated that the leading commercially available free skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 240 detergents are of comparable mildness. a recently published 21-day cumulative irritation test showed that fabrics washed with tide pods free & gentle (tpfg) were as mild to skin as those washed with all free clear (afc).18 new in vitro methodologies have been proposed as a surrogate for in vivo testing for laundry detergent mildness.19 while in vitro methods can be useful tools for rapid screening of large numbers of surfactants and product formulations, the ultimate test of mildness is contact with human skin in a controlled study with sufficient skin assessment end points to assure safe use on sensitive skin.11,20-22 while the mildness of commercially available free detergents is comparable, they vary considerably in their ability to remove laundry soils. a detergent’s ability to clean is influenced by several factors, including shifts in consumer trends and advancements in technology. for instance, the rise of synthetic fabrics in clothing, such as polyester which are hydrophobic and more attracted to oils than hydrophilic, natural fibers like cotton, has created the need for new formulations. furthermore, changes in washing machine technology, mainly the rise of high efficiency (he) washing machines with lower, cooler wash water levels and temperatures, have had an influence as well. these changes require alterations in detergent formulations to provide optimal cleaning performance. therefore, to adequately measure the cleaning efficacy of formulations, it is important to consider all of these factors. better cleaning and compliance with dermatologist recommendations consumer satisfaction with laundry detergents is predominately driven by cleaning performance.23 many people with sensitive skin believe they must compromise cleaning performance for mildness on skin. an internet survey of 3,175 people in the us who are responsible for their laundry and laundry product purchasing conducted from late 2014 through early 2015 showed that 39% of free detergent users are not satisfied with their detergent’s cleaning performance. additionally, 42% of free detergent users are not satisfied with their current product’s ability to remove difficult stains.24 consumer purchase data shows that when consumers switch from the us-market leading free liquid detergent, all free clear, they will switch to a non-free detergent almost 60% of the time.25 an internet survey of 404 us households with sensitive skin conducted in december of 2017 shows that a strong majority of these consumers would prefer to use a free detergent that cleans better, would be willing to pay more for that detergent, and would consider it a better value. notably, these consumers (98.8%) also said that they would be more likely to consistently use a detergent that cleans better (table 1). due to these consumer trends and insights, a detergent that is mild on skin and provides better cleaning performance represents a product that may help to drive patient compliance with dermatologists’ recommendations for free detergents. recommendations skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 241 table 1. the influence of cleaning performance on consumer behavior comparing the cleaning performance of commercial free detergents astm international is a voluntary industry organization that publishes a standard guide for evaluating the stain removal performance of laundry detergents designed for in-home use.26 these guidelines include the selection, preparation, application and examination of various types of stains on different types of test fabrics and testing in both traditional top load washing machines and in front load he machines to simulate consumer experience as closely as possible. as the relative effectiveness of various laundry products will be influenced by the nature of the fabric, it is pointed out that testing may encompass more than one fiber composition. for reference, the three fabric types most common for the us laundry are polyester/cotton blends, 100% cotton, and 100% polyester. the guidelines recommend that at least 6 stains should be used in detergent cleaning evaluations and that stains may be selected to indicate various cleaning objectives, such as representing a specific cleaning mechanism or predicting an important consumer stain or stain class. astm guidelines were followed to evaluate the stain removal performance of 3 free detergents available at retail in the us: tide pods free & gentle detergent pac (tpfg), all free clear liquid detergent (afc), and purex free and clear liquid detergent (pfc). two of these free detergents are also available at retail in canada: tpfg and pfc. while afc and pfc are formulated as liquids, tpfg is formulated as a highly concentrated laundry detergent pac encased in a water-dissolvable membrane. astm guidelines recommend using at least 6 stains, whereas free detergents in this manuscript were evaluated across 18 stains to better predict real-world consumer experience. free detergents were purchased in late 2017 at retail locations in the us within 4 weeks of testing and dosed according to the manufacturer’s label instructions for a medium wash load. evaluations were performed in traditional top-loader (tl) washing machines and in front-loader he washing machines, and on fabric swatches composed of 100% cotton or polycotton (a blend of 50% cotton/50% polyester; empirical manufacturing company, incorporated; cincinnati, ohio, usa) on the normal cycle. stain strips for testing included 18 stains representing 10 technical stain categories, including food grease, sebum, grass, particulates, and colored beverages/food, among others. stain strips were washed one time in either a whirlpool duet high efficiency (he) washing machine (whirlpool corporation, comparison skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 242 benton harbor, michigan, usa) on the normal cycle at 77°f wash/60°f rinse, or in a kenmore series 600 top-loader washing machine (sears holdings corporation, hoffman estates, illinois, usa) on the normal cycle at 86°f wash/60°f rinse with a manufacturer recommended dose for a medium laundry load of either tpfg, afc or pfc using a mineral mixture representing the average water hardness in the usa (17.1ppm of minerals, 4:1 ratio of cacl2:mgcl2). after the wash, fabrics were dried in a commercial clothes dryer on normal for 30 min. the stain removal index (sri) was calculated using instrumental measurements of the reflectance of the stained fabrics and the unstained areas of the fabrics (for reference) before and after machine washing and drying. treatment comparisons were made between tpfg and the other free detergents for each stain separately. the response analyzed was the average stain removal index across internal reps for each combination of machine, run, and treatment. a mixed model with fixed effects for treatment and run and a random effect for machine was used to model the data. the following set of hypotheses were tested at a type i error rate of 0.05 for each pair of treatments, adjusting for the multiple treatment comparisons using tukey’s “honestly significant difference” (hsd) procedure: null hypothesis = treatment x and treatment y are the same with respect to mean sri; alternative hypothesis = treatment x and treatment y are different with respect to mean sri. tpfg consistently outperformed afc and pfc across a wide variety of stain categories, across 2 fabrics and 2 types of washing machines. stains in which the sri was significantly higher (that is, significantly more of the stain was removed) with tpfg are indicated in green, stains in which the differences between treatments were not significantly different are indicated by a lack of color, and stains in which the sri for tpfg was significantly lower (that is, significantly less of the stain was removed) are indicated in red. across both washing machines and both fabrics, tpfg outperformed afc on 7 stains and underperformed on 2 stains, showing either better or parity performance on the remaining 9 stains (table 2). across both washing machines and both fabrics, tpfg outperformed pfc on 13 stains, showing either better or parity performance on 3 stains and worse or parity performance on 2 stains (table 3). notably, tpfg outperformed pfc on the removal of sebum, a major source of fabric malodor, across both washing machines and both fabrics and outperformed afc on cotton fabrics in an he washing machine. interestingly, tpfg performed poorly on the mustard stain which is a ph-depended stain and as such is removed better with detergents like afc and pfc which are formulated at a higher ph than tpfg, which has a more neutral ph of 7.8. scanning electron microscopy analysis of cleaning performance grease and oil residues left behind by poorly performing laundry detergents can attract loose soils in the wash water and cause build-up on fabrics over time. to visualize soils on fibers, we washed the polycotton fabric swatches in a kenmore 600 series top-loader washing machine with 1 dose of either tpfg or 1 dose of afc along with a analysis skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 243 table 2. stain removal comparisons of tide pods free & gentle detergent pac (tpfg) vs. all free clear (afc) liquid detergent. skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 244 table 3. stain removal comparisons of tide pods free & gentle detergent pac (tpfg) vs purex free clear (pfc) liquid detergent. skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 245 technical swatch (empirical manufacturing company, cincinnati, ohio, usa) embedded with 40g of soils (28 g of artificial body soil, 4 ml of vegetable oil, and 9 ml of a clay slurry) mimicking consumer relevant laundry soils equivalent to those found in a typical 6 pound load of laundry. the test swatches were washed on a normal cold cycle (60°f wash/60°f rinse) at 7 gpg water hardness then dried on the normal cycle for 30 min. this was repeated a total of 8 times. scanning electron microscopy (sem) was utilized to visualize the soil residues adhering to the fibers on the treated fabrics (hitachi s-4800, secondary electron detection, 2kv acceleration voltage; hitachi, ltd., tokyo, japan) at 2000x magnification. fabric samples were sputter coated 150 seconds with 60:40 au:pd (gatan alto 2500) to minimize sample charging. sem evaluations of 50% polyester/50% cotton swatches washed 8 times with technical soil swatches showed noticeably less buildup of soils after treatment with tpfg vs. afc. when examining the polyester fibers via sem, there is more soil buildup on the swatch washed with afc vs. tpfg (figures 1 & 2). similarly, when examining the cotton fibers via sem, there is more soil buildup on the swatch washed with afc vs. tpfg (figures 3 & 4). in north america an overwhelming majority of dermatologist recommend the use of free detergents for their patients with sensitive skin, yet up until now very little research has been done to determine which factors can help to drive patient compliance with that recommendation. retail purchase data figure 1. sem scan of polyester fibers on polycotton swatch washed with afc *image has been colorized figure 2. sem scan of polyester fibers on polycotton swatch washed with tpfg *image has been colorized demonstrate that all laundry detergents formulated for people with sensitive skin may not adequately serve the needs of this patient population. while mildness is comparable across detergents, cleaning performance is highly variable and can influence patient purchase decisions. free detergent users report being unsatisfied with their free laundry detergents and up to 60% will switch to purchasing non-free conclusion skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 246 figure 3. sem scan of cotton fibers on polycotton swatch washed with afc *image has been colorized figure 4. sem scan of cotton fibers on polycotton swatch washed with tpfg *image has been colorized detergents, going against dermatologist recommendations. a large-scale survey of us households with sensitive skin showed that 98.8% would be more likely to consistently use a detergent that cleans better. studies reported in this paper demonstrated that tide pods free & gentle provided significantly better cleaning performance compared to two other leading free detergents across a variety of testing methodologies. the experimental design incorporated the broad range of stain categories free detergent users experience, the fiber composition of fabrics in laundry loads, as well as the types of washing machines present in their homes. by providing superior cleaning performance, tide pods free & gentle laundry pacs may help to improve compliance with dermatologist recommendations for use of a free detergent for their patients with sensitive skin. this is especially important for this patient population, as a change to a non-free laundry detergent may potentially increase the likelihood of skin irritation. conflict of interest disclosures: all authors are employees of the procter & gamble company funding: this work was funded by the procter & gamble company acknowledgments: the authors wish to thank jenny miller, eric moorhead, fabrizio meli, sol escobar, will shearouse, and jack english for their assistance in the preparation of this manuscript. corresponding author: mary begovic johnson, ms 5299 spring gove avenue; cincinnati, ohio; 45217 phone: 513-602-4252 email: johnson.mb.3@pg.com references: 1. farage, m. a. (2009). how do perceptions of sensitive skin differ at different anatomical sites? an epidemiological study. clinical and experimental dermatology, 34(8), e521–e530. 2. misery, l., sibaud, v., merial-kieny, c., & taieb, c. (2011). sensitive skin in the american population: prevalence, clinical data, and role of the dermatologist: sensitive skin in usa. international journal of dermatology, 50(8), 961– 967. 3. farge, m. a., & robinson, m. k. (2012). sensitve skin: intrinsic and extrinsic contrbutors. in m. lodén & h. i. maibach (eds.), treatment of dry skin syndrome (pp. 95–109). berlin, heidelberg: springer berlin heidelberg. skin may 2020 volume 4 issue 3 copyright 2020 the national society for cutaneous medicine 247 4. mohamoud, a. a., & andersen, f. (2017). allergic contact dermatitis caused by textile dyes mimicking atopic dermatitis: allergic contact dermatitis caused by textile dyes. contact dermatitis, 76(2), 119–120. 5. belsito, d. v., fransway, a. f., fowler, j. f., sherertz, e. f., maibach, h. i., mark, j. g., nethercott, j. r. (2002). allergic contact dermatitis to detergents: a multicenter study to assess prevalence. journal of the american academy of dermatology, 46(2), 200–206. 6. krakowski, a., & eichenfield, l.f. (2010). atopic dermatitis basics: three common myths debunked. practical dermatology for pediatrics. may/june, 39-42. 7. p&g data on file. us data is based on iqvia ™ provoice january 2018 cumulative 12-month data. canadian data is based on an internet survey of 150 dermatologists licensed to practice in canada conducted in january 2018. 8. ertel, k. (2000). modern skin cleansers. dermatologic clinics, 18(4), 561–575. 9. yamaguchi, f. watanabe, s., harada, f., miyake, m., yoshida, m. & okano, t. (2014). in vitro analysis of the effect of alkyl-chain length of anionic surfactants on the skin by using a reconstructed human epidermal model. journal of olea science, 63(10), 995-1004. 10. mukhopadhyay, p. (2011). cleansers and their role in various dermatological disorders. indian journal of dermatology, 56(1), 2. 11. crawford, c., & zirwas, m.j. (2014). laundry detergents and skin irritancya comprehensive review, 12(1), 23-31. 12. adrio, j., & demain, a. (2014). microbial enzymes: tools for biotechnological processes. biomolecules, 4(1), 117–139. 13. basketter, d. a., english, j. s. c., wakelin, s. h., & white, i. r. (2008). enzymes, detergents and skin: facts and fantasies. british journal of dermatology, 158(6), 1177–1181. 14. bowman, j.p., berger, r.s., mills, o.h. (2003). the 21-day human cumulative irritation test can be reduced to 14 days without loss of sensitivity. j. cosmet. sci., 54, 443-449. 15. mcnamee, p. m., api, a. m., basketter, d. a., frank gerberick, g., gilpin, d. a., hall, b. m., robinson, m. k. (2008). a review of critical factors in the conduct and interpretation of the human repeat insult patch test. regulatory toxicology and pharmacology, 52(1), 24–34. 16. marzulli, f. n., & maibach, h. i. (1980). further studies of effects of vehicles and elicitation concentration in experimental contact sensitization testing in humans. contact dermatitis, 6(2), 131–133. 17. basketter, d. a. (2009). the human repeated insult patch test in the 21st century: a commentary. cutaneous and ocular toxicology, 28(2), 49–53. 18. brink, s., wang, y., blum, b., baccam, m., varbanov, a., boeh, v., wang, y., christman, j., cella, c.e., johnson, m.b., farage, m.a. (2019). clinical skin mildness evaluations of direct and indirect exposure to two commercial laundry detergents with markedly different ph designed for sensitive skin using a hand-laundering model. journal of cosmetic science, 70, 1-17. 19. fowler, j.f., zirwas, m.j., napolitano, l., coopeepstein, j. and russell, m. (2017). a new approach to formulating a milder laundry detergent for patients with sensitive skin. j am acad dermatol. 76s, 17. 20. demetrulias, j., donnelly, t., morhenn, v., jessee, b., hainsworth, s., casterton, p., bernhofer, l., martin, k. and decker, d. (1998). skin2 -an in vitro human skin model: the correlation between in vivo and in vitro testing of surfactants. exp dermatol. 7, 18-26. 21. fujimura, t., shimotoyodome, y., nishijima, t., sugata, k., taguchi, h. and moriwaki, s. (2017). changes in hydration of the stratum corneum are the most suitable indicator to evaluate the irritation of surfactants on the skin. skin res technol. 23, 97-103. 22. gabard, b., chatelain, e., bieli, e. and haas, s. (2001). surfactant irritation: in vitro corneosurfametry and in vivo bioengineering. skin res technol. 7, 49-55. 23. ferri, a., osset, m., abeliotis, k., amberg, c., candan, c., owens, j., & stamminger, r. (2016). laundry performance: effect of detergent and additives on consumer satisfaction. tenside surfactants detergents, 53(4), 375–386. 24. p&g data on file 25. neilsen 2017 laundry detergent retail sales data; www.nielsen.com 26. astm d4265-14. standard guide for evaluation stain removal performance in home laundering. accessed from: https://www.astm.org/standards/d4265.htm fig ure 6 effic acy: enth esiti s -1.6 -1.4 -1.2 -1 -0.8 -0.6 -0.4 -0.2 0 * baseline, mean ± sd til 200 mg q4w 3.1 ± 1.7 til 200 mg q12w 2.8 ± 1.7 til 100 mg q12w 3.2 ± 1.8 til 20 mg q12w 3.1 ± 1.7 pbo 2.8 ± 1.8 4 weeks 12 weeks 24 weeks −0.4 −0.2 0 −0.8 −0.6 −1.2 −1 −1.4 −1.6 c ha ng e fr om b as el in e to ta l l e i s co re figure 4. mean change in tender and swollen joint counts by treatment and timepoint shown for randomized patients who received ≥1 dose of study drug; values at week 0 represent baseline. *p <0.05; †p <0.001 vs pbo. ls, least squares; pbo, placebo; q4w, every 4 weeks; q12w, every 12 weeks; se, standard error; til, tildrakizumab. randomized, double-blind, placebo-controlled, multiple-dose, phase 2b study to demonstrate the safety and efficacy of tildrakizumab, a high-affinity anti–interleukin-23p19 monoclonal antibody, in patients with active psoriatic arthritis philip j. mease,1 saima chohan,2 ferran j. garcía fructuoso,3 alice b. gottlieb,4 richard c. chou,5 alan m. mendelsohn,6 michael e. luggen7,8 1swedish medical center/providence st. joseph health and university of washington, seattle, wa, usa; 2arizona arthritis and rheumatology research, pllc, phoenix, az, usa; 3hospital cima sanitas, barcelona, spain; 4department of dermatology, icahn school of medicine at mount sinai, new york, ny, usa; 5division of allergy, immunology and rheumatology, university at buffalo school of medicine and biomedical sciences, buffalo, ny, usa; 6sun pharmaceutical industries, inc., princeton, nj, usa; 7cincinnati rheumatic disease study group, inc., cincinnati, oh, usa; 8university of cincinnati college of medicine, cincinnati, oh, usa background • psoriatic arthritis (psa) is a progressive, chronic inflammatory arthritis with an estimated prevalence of 0.3%– 1% globally1,2 • there is an unmet need for therapeutics that address all of the manifestations of psa and have an acceptable safety profile2,3 • tildrakizumab is an anti–interleukin (il)-23p19 monoclonal antibody approved in the us, europe, and australia for treatment of moderate to severe plaque psoriasis4,5 • a randomized, double-blind, multiple-dose, placebo-controlled, phase 2b study (nct02980692) to evaluate the efficacy and safety of tildrakizumab for the treatment of psa was recently completed objective • to evaluate the efficacy and safety of tildrakizumab in patients with active psa at 24 weeks from the interim analysis of the randomized, double-blind, placebo-controlled, multiple-dose, phase 2b trial methods • study design is summarized in figure 1 figure 1. study design pbo, placebo; q4w, every 4 weeks; q12w, every 12 weeks; til, tildrakizumab. • placebo was given every 4 weeks (q4w) to patients receiving tildrakizumab every 12 weeks (q12w) to maintain blinding • patients were stratified by prior anti-tumor necrosis factor (tnf)-α use (yes/no; prior use capped at 30% of total patients) and baseline body weight (≤90 kg/>90kg) • patients who failed to show minimal response to treatment (<10% improvement from baseline in swollen and tender joint counts) at week 16 were allowed to adjust background medications (methotrexate [mtx], leflunomide, or oral corticosteroids), according to the maximum permitted daily dose inclusion criteria • patients ≥18 years old with a diagnosis of psa (classification of psoriatic arthritis [caspar] criteria)6 for ≥6 months, and with ≥3 tender and ≥3 swollen joints as evaluated by an independent assessor • criteria for permitted background medications: — stable use of nonsteroidal anti-inflammatory drugs (including as needed use) — use of mtx (≤25 mg per week) or leflunomide ≤20 mg per day for ≥3 months and on a stable dose for ≥8 weeks prior to start of treatment with study drug — stable use of oral corticosteroids (prednisone ≤10 mg per day) for ≥4 weeks prior to start of treatment with study drug — ability to maintain current background treatment for the first 24 weeks of the study exclusion criteria • patients with prior use of the following medications were excluded: — more than 1 biologic treatment, or any prior use of anti–il-17, il-23, or il-12/il-23 p40 biologic therapies for psoriasis/psa (eg, secukinumab, ustekinumab, ixekizumab, brodalumab, or investigational drugs) — etanercept, infliximab and all other anti-tnf therapies within 4 weeks, 8 weeks, and 3 months, respectively — b-cell and t-cell depleting agents within 12 months of screening; other biologic therapies within the longer of 5 half-lives or 3 months of initiating tildrakizumab — apremilast or other approved or investigational medications for treatment of psa within the longer of 5 halflives or 30 days of initiating tildrakizumab • presence of major chronic inflammatory or connective tissue disease other than psa (eg, rheumatoid arthritis), concurrent uncontrolled systemic disease, history of hepatitis b/c or human immunodeficiency virus infections, or history of noncutaneous or in situ cervical/breast ductal malignancies <5 years in the past • presence of prespecified abnormal laboratory parameters, use of nonpermitted drugs (including high-potency opioid analgesics, parenteral corticosteroids, and live vaccines) within 28 days of start of treatment efficacy assessments • the proportion of patients at week 24 with ≥20%, ≥50% and ≥70% improvement in american college of rheumatology criteria (acr20/50/70) • the proportion of patients achieving ≥75%, ≥90%, and 100% improvement in psoriasis area and severity index (pasi 75/90/100); in patients with measurable psoriasis, defined as bsa ≥3% at baseline • improvements in sixty-six swollen and 68 tender joint counts (sjc, tjc) • patient-rated present pain level due to arthritis (improvements in visual analog scale [0–100 mm]) • leeds enthesitis index (improvements in lei) safety assessments • treatment-emergent aes (teaes) were monitored (coded by medical dictionary of regulatory activities v20.1) and laboratory assessments were performed throughout the study • analyses were based on the actual treatment received; missing safety data were not replaced results • in total, 391/500 patients screened met inclusion criteria • patient demographics and baseline disease characteristics were consistent across treatment arms (table 1) table 1. demographics and baseline clinical disease characteristics til 200 mg q4w (n = 78) til 200 mg q12w (n = 79) til 100 mg q12w (n = 77) til 20 mg q12w (n = 78) pbo (n = 79) age, years, mean ± sd 50.1 ± 13.3 49.3 ± 11.2 49.2 ± 11.9 47.2 ± 13.4 48.1 ± 13.3 female, n (%) 46 (59.0) 37 (46.8) 47 (61.0) 41 (52.6) 44 (55.7) race, n (%) white black or african american other 76 (97.4) 0 2 (2.6) 78 (98.7) 0 1 (1.3) 75 (97.4) 1 (1.3) 1 (1.3) 75 (96.2) 1 (1.3) 2 (2.6) 74 (93.7) 3 (3.8) 2 (2.5) weight, kg, mean ± sd 85.1 ± 19.7 87.1 ± 19.5 83.6 ± 18.9 85.1 ± 18.1 85.3 ± 20.2 bmi, kg/m2, mean ± sd 30.1 ± 6.5 30.2 ± 6.5 29.5 ± 6.8 29.4 ± 5.2 29.5 ± 6.0 duration of psa, years, mean ± sd 6.9 ± 7.3 6.8 ± 6.3 6.3 ± 7.2 6.6 ± 6.7 7.3 ± 8.0 prior anti–tnf-α therapy, n (%)a 18 (22.8) 17 (21.8) 19 (23.8) 19 (24.4) 18 (23.7) swollen joint count, mean ± sd 10.4 ± 7.4 10.0 ± 8.0 11.0 ± 8.2 9.4 ± 6.4 11.8 ± 9.8 tender joint count, mean ± sd 16.6 ± 11.9 19.5 ± 13.9 21.3 ± 14.8 19.0 ± 13.0 19.7 ± 14.7 patient gada, mean ± sd 57.8 ± 18.3 61.1 ± 20.7 60.3 ± 20.2 61.9 ± 17.4 65.2 ± 18.1 physician gada, mean ± sd 54.0 ± 16.1 55.4 ± 16.2 57.3 ± 17.3 59.4 ± 14.4 59.5 ± 15.6 patient pain assessment, mean ± sd 55.4 ± 19.1 59.6 ± 23.5 59.2 ± 22.1 60.9 ± 19.7 64.2 ± 20.4 enthesitis (lei >0), n (%) 48 (61.5) 43 (54.4) 51 (66.2) 55 (70.5) 43 (54.4) enthesitis score (lei >0), mean ± sd 3.1 ± 1.7 2.8 ± 1.7 3.2 ± 1.8 3.1 ± 1.7 2.8 ± 1.8 bsa, (%), mean ± sd 11.9 ± 16.0 9.0 ± 12.4 12.8 ± 16.0 10.4 ± 14.1 8.2 ± 12.2 bsa ≥3%, n (%) 53 (67.9) 44 (55.7) 54 (70.1) 41 (52.6) 42 (53.2) pasi, mean ± sdb 7.6 ± 9.8 6.2 ± 7.4 8.8 ± 9.5 6.6 ± 7.0 5.0 ± 6.5 haq score, mean ± sd 1.0 ± 0.6 1.0 ± 0.6 1.0 ± 0.7 1.1 ± 0.6 1.2 ± 0.6 afor prior anti–tnf-α therapy, total patients analyzed (n) = 79, 78, 80, 78, and 76 for til 200 mg q4w, til 200 mg q12w, til 100 mg, til 20 mg, and pbo. bfor analysis of baseline pasi, all patients were analyzed, regardless of % bsa involved; n = 75, 79, 76, 75, and 75 for til 200 mg q4w, til 200 mg q12w, til 100 mg, til 20 mg, and pbo. shown for randomized patients who received ≥1 dose of study drug. bmi, body mass index; bsa, body surface area; gada, global assessment of disease activity; haq, health assessment questionnaire disability index; lei, leeds enthesitis index; pasi, psoriasis area and severity index; pbo, placebo; psa, psoriatic arthritis; q4w, every 4 weeks; q12w, every 12 weeks; sd, standard deviation; til, tildrakizumab; tnf, tumor necrosis factor. • concomitant use of other antirheumatic medications in the total study population included leflunomide only (3.8%), leflunomide + prednisone/prednisolone (0.3%); mtx only (51.4%), mtx + prednisone/prednisolone (5.1%), sulfasalazine only (0.3%), prednisolone only (2.1%), sulfasalazine + leflunomide (0.3%) • at week 24, there was a significantly greater proportion of acr20, acr50, and acr70 responders among all tildrakizumab treatment arms vs placebo except for tildrakizumab 20 mg q12w for acr70 (figure 2) figure 2. proportion of patients achieving acr20, acr50, and acr70 responses by treatment and timepoint shown for randomized patients who received ≥1 dose of study drug. *p <0.05; †p <0.001; ‡p <0.0001 vs pbo. acr, american college of rheumatology response criteria; pbo, placebo; q4w, every 4 weeks; q12w, every 12 weeks; til, tildrakizumab. • at week 24, among patients with ≥3% bsa involvement at baseline, there was a significantly greater proportion of pasi 75, pasi 90, and pasi 100 responders among those receiving any dose of tildrakizumab compared with those receiving placebo (figure 3) — the proportion of responses in placebo-treated patients were low across all pasi outcomes figure 3. proportion of patients achieving pasi 75, pasi 90, and pasi 100 responses by treatment and timepoint response rates calculated in patients with bsa ≥3% at baseline, missing responses were imputed as nonresponses. *p <0.05; †p <0.001; ‡p <0.0001 vs pbo. bsa, body surface area; pasi, psoriasis area and severity index; pbo, placebo; q4w, every 4 weeks; q12w, every 12 weeks; til, tildrakizumab. • tildrakizumab 100 and 200 mg q12w significantly reduced tender joint counts vs placebo (figure 4) • tildrakizumab 100 mg q12w and 200 mg q4w significantly reduced swollen joint counts vs placebo (figure 4) • all tildrakizumab arms improved patient pain from baseline (p <0.05 vs placebo except tildrakizumab 20 q12w, figure 5) figure 5. mean change in patient pain by treatment and timepoint shown for randomized patients who received ≥1 dose of study drug; values at week 0 represent baseline. *p <0.05; †p <0.001 vs pbo. ls, least squares; pbo, placebo; q4w, every 4 weeks; q12w, every 12 weeks; se, standard error; til, tildrakizumab. s cr ee ni ng r an do m iz at io n 1: 1: 1: 1: 1 (b as el in e) til 200 mg q4w til 200 mg q12w til 100 mg q12w til 20 mg q12w pbo q4w −4 0 24weeks screening double-blind placebo-controlled primary endpoint til 200 mg q12w til 200 mg q12w double-blind follow-up 48 day 1 16 presented at fall clinical dermatology conference for pas & nps 2020, april 3–5, orlando, fl, usa • tildrakizumab 200 q4w significantly improved lei by 71.2% (p <0.05, figure 6) figure 6. enthesitis by treatment and timepoint *p <0.05 compared with pbo. data represents change from baseline ± sd. lei, leeds enthesitis index; pbo, placebo; q4w, every 4 weeks; q12w, every 12 weeks; sd, standard deviation; til, tildrakizumab. • no deaths or discontinuations due to teaes were reported (table 2) table 2. summary of safety at week 24 any til arm (n = 312) pbo (n = 79) any teae 156 (50.0) 34 (43.0) any serious teaes 7 (2.2) 2 (2.5) any teae related to treatment 35 (11.2) 10 (12.7) discontinuation due to teaes 0 0 serious infections 1 (0.3)a 0 major adverse cardiac events 0 0 malignancy 0 0 deaths due to teaes 0 0 achronic tonsillitis. data are shown as n (%) for randomized patients who received ≥1 dose of study drug. pbo, placebo; teae, treatment-emergent adverse event; til, tildrakizumab. • the most commonly reported teaes were nasopharyngitis (17 [5.4%] tildrakizumab-treated vs 5 [6.3%] placebo-treated), headache (15 [4.8%] vs 2 [2.5%]), and hypertension (11 [3.5 %] vs 4 [5.1%]), respectively • there were no significant elevations in laboratory parameters that led to a serious teae designation • at 24 weeks, there were no reports of candidiasis, inflammatory bowel disease, major adverse cardiac events, significantly increased liver enzymes, malignancies, or suicidal ideation conclusions • by week 24, all 4 dose categories of tildrakizumab were significantly more efficacious than placebo in treatment of joint and skin manifestations of psa • there was a clear separation in acr20 improvements from baseline between tildrakizumab and placebo as early as 8 weeks • shortening the dosing interval from q12w to q4w for the 200-mg dose did not result in a measurable increase in skin or joint response scores • tildrakizumab was well tolerated with low rates of teaes reported references 1) ogdie a, et al. rheum dis clin north am. 2015;41(4):545−68; 2) singh ja, et al. arthritis care res (hoboken). 2019;71(1):2−29; 3) ogdie a, et al. curr rheumatol rep. 2017;19(4):21; 4) reich k, et al. lancet. 2017;390(10091):276−88; 5) kopp t, et al. nature. 2015;521(7551):222−6; 6) taylor w, et al. arthritis rheum. 2006;54(8):2665−73. acknowledgments we thank patients for their participation. the studies were funded by merck sharp & dohme corp., a subsidiary of merck & co., inc., kenilworth, nj, usa. analyses were funded by sun pharmaceutical industries, inc., princeton, nj, usa. editorial support was provided by claire daniele, phd, cmpp, of alphabiocom, llc, and funded by sun pharmaceutical industries, inc. disclosures pjm has received research grants, consulting fees, and/or speaker fees from abbvie; amgen; bristol-myers squibb; celgene; galapagos; genentech; gilead; janssen; leo; eli lilly; merck; novartis; pfizer; sun pharmaceutical industries, inc.; and ucb. abg has current consulting/advisory board agreements with abbvie; allergan; avotres therapeutics; beiersdorf; boehringer ingelheim; bristol-myers squibb; celgene corp.; dermira; eli lilly; incyte; janssen; leo; novartis; reddy labs; sun pharmaceutical industries, inc.; ucb; valeant; and xbiotech; and has received research/educational grants from boehringer ingelheim, incyte, janssen, novartis, ucb, and xbiotech. sc has no conflicts of interest to disclose. fjgf has received research grants, consulting fees, and/or speaker fees from abbvie, eli lilly, gedeon richter, medimmune, nichi-iko, pfizer, sanofi-aventis, takeda, and ucb. rcc receives consulting fees from sun pharmaceutical industries, inc. amm is employed by sun pharmaceutical industries, inc. and holds individual shares in johnson and johnson. mel has received research grants, consulting fees, and/or speaker fees from abbvie; amgen; eli lilly; genentech; nichi-iko; novartis; pfizer; r-pharm; and sun pharmaceutical industries, inc. −15 −10 −5 0 week 1 4 8 12 16 20 240 * **l s m ea n ch an ge fr om ba se lin e ± s e til 200 mg q4w til 200 mg q12w til 100 mg q12w til 20 mg q12w pbo tender joint counts swollen joint counts week 1 4 8 12 16 20 24 ** ** * **† til 200 mg q4w til 200 mg q12w til 100 mg q12w til 20 mg q12w pbo −15 −10 −5 0 ls m ea n ch an ge fr om ba se lin e ± s e 79.5 77.2 71.4 73.1 50.6 0 20 40 60 80 100 week 1 4 8 12 16 20 24 * ** * * ** ** * † †‡ ‡‡ r es po ns e ra te (% ) til 200 mg q4w til 200 mg q12w til 100 mg q12w til 20 mg q12w pbo 52.6 50.6 45.5 39.7 24.1 0 20 40 60 80 week 1 4 8 12 16 20 24 * †† * † † ‡†† ****re sp on se ra te (% ) * til 200 mg q4w til 200 mg q12w til 100 mg q12w til 20 mg q12w pbo r es po ns e ra te (% ) 28.2 29.1 22.1 16.7 10.1 0 20 40 60 80 week 1 4 8 12 16 20 24 * * *** * ‡ *** ** til 200 mg q4w til 200 mg q12w til 100 mg q12w til 20 mg q12w pbo acr20 acr50 acr70 pasi 75 pasi 90 pasi 100 * ** * ‡ ‡ * ‡ ‡ ‡ ** week 0 10 20 30 40 50 60 70 80 90 100 1 4 12 16 24 r es po ns e ra te (% ) 64.2 79.6 55.6 46.3 16.7 til 200 mg q4w til 200 mg q12w til 100 mg q12w til 20 mg q12w pbo 47.2 50.0 38.9 36.6 7.1 * **** ‡ ‡ † week 0 10 20 30 40 50 60 70 80 90 100 1 4 12 16 24 r es po ns e ra te (% ) til 200 mg q4w til 200 mg q12w til 100 mg q12w til 20 mg q12w pbo 30.2 25.0 25.9 22.0 4.8 *** * week 0 10 20 30 40 50 60 70 80 90 100 1 4 12 16 24 r es po ns e ra te (% ) til 200 mg q4w til 200 mg q12w til 100 mg q12w til 20 mg q12w pbo baseline, mean ± sd til 200 mg q4w 55.4 ± 19.1 til 200 mg q12w 59.6 ± 23.5 til 100 mg q12w 59.2 ± 22.1 til 20 mg q12w 60.9 ± 19.7 pbo 64.2 ± 20.4 −40 −30 −20 −10 0 week 1 4 8 12 16 20 240 * * * * * * * † * * * * * ** * * ls m ea n ch an ge fr om ba se lin e ± s e til 200 mg q4w til 200 mg q12w til 100 mg q12w til 20 mg q12w pbo an observational study of the safety and efficacy of tissue stabilized-guided subcision to improve the appearance of cellulite roy g geronemus,1 jeremy a brauer,1 suzanne l kilmer,2 simeon h wall jr,3 jeremy b green,4 joel l cohen,5 robert a weiss,6 tina s alster,7 michael s kaminer,8 1laser & skin surgery of new york; new york, ny; 2laser and skin surgery center of northern, ca; sacramento, ca; 3the wall center for plastic surgery; shreveport, la; 4skin associates of south florida; coral gables, fl; 5aboutskin research, llc; englewood, co; 6maryland laser skin and vein; hunt valley, md; 7washington institute of dermatological laser surgery; washington, dc; 8skincare physicians; chestnut hill, ma • ts-gs is fda cleared for the long-term improvement in the appearance of cellulite on the buttocks and thighs, with no loss of benefit for up to 3 years (tables 1 and 2)1-3 • the purpose of this observational study was to collect data on ts-gs treatment administration, safety, and effectiveness in real-life clinical practice figure 1. ts-gs schematic1 anesthesia needle assembly anesthesia guidance platform suction pump connection vacuum chamber reversible lid release micro-blade assembly reliease guidance platform (1 of 2) motor module • cellulite refers to the dimpled appearance of skin which is estimated to affect approximately 95% of post-pubertal women of all races • the appearance of cellulite has been associated with significant social stigma and can adversely affect self-esteem • tissue stabilized-guided subcision (ts-gs; cellfina(r) system, ulthera, inc.) builds on the proven approach of dermal undermining, or subcision; the system is designed to provide vacuum-assisted control of both the depth and area of tissue release to allow for precise, reproducible and consistently effective treatment results (figure 1)1 table 1. pivotal trial efficacy. the mean improvement on the cellulite severity scale remained constant through 3 years of follow-up. primary endpoint 3m 1 year 2 year 3 year average improvement (0-5 scale) 2.1 points 2.0 points 2.0 points 2.0 points % of ≥ 1 grade improvement (none, mild, moderate, severe) 93% 94% 88.5% 91% table 2. pivotal trial subject satisfaction. most subjects (≥93%) remained satisfied or very satisfied with the results of their treatment through 3-years. satisfaction baseline (n=55) 3d (n=55) 14d (n=54) 1m (n=54) 3m (n-55) 6m (n=52) 1 y (n=50) 2y (n=54) 3y (n=45) very unsatisfied 28 1 0 0 0 0 0 0 0 unsatisfied 27 10 1 2 1 2 0 0 0 neutral 0 22 16 9 7 4 3 2 3 satisfied 0 18 25 29 26 25 24 26 23 very satisfied 0 4 12 14 21 21 23 24 19 % satisfied 0% 33% 69% 80% 85% 88% 94% 96% 93% background and objective • prospective, multi-center, non-randomized, standard of care, observational registry study • 53 female subjects were enrolled at 8 sites and treated using a ts-gs device by investigator or sub-investigator according to the sites’ standard of care registry endpoints and analyses • primary: subject-assessed global aesthetic improvement score (gais) at day 180. • secondary: physician global aesthetic improvement score (gais) at day 180 post-treatment quality of life questionnaire at the treatment visit, 30, 90, and 180 day follow-up visits to determine effect of celllulite on clothing (0=no effects at all; 10=very much affects) subjects were asked to rate their level of pain from 0 -10 (0 = no pain and 10 = worst possible pain) • adverse events and expected treatment effects (effects more than moderate in severity were considered adverse events) single site analyses • one of the registry sites conducted additional pilot analyses of efficacy including: 3d vectra imaging of the treatment areas to quantitatively assess changes in dimple depth and volume blinded investigator assessment of 2d photography • a total of 13 patients at this site were included in the 3d image analyses and the blinded investigator assessment of 2d photography single site analysis: 3d analysis of dimple depth and volume • 145 dimples treated with ts-gs in 13 subjects; 3d vectra image analyses were conducted using standardized photos • mean improvement in volume was 67.4% • mean improvement in height of the dimple was 58.4% registry design 3d analysis 3d analysis results single site analysis: blinded physician assessment of improvement • at 180 days, the majority of patients, the majority of patients were rated >50% improved by blinded physicians (both dimple depth and overall improvement; table 7) table 7. blinded physician assessment at 180 days. the majority of patients were rated >50% improved in terms of dimple depth and overall improvement. degree of improvement improvement overall, n (%) (n=13) improvement in dimple depth, n (%) (n=13) 4 (76-100%) 4 (30.8%) 4 (30.8%) 3 (51-75%) 4 (30.8%) 5 (38.4%) 2 (26-50%) 5 (38.4%) 4 (30.8%) 1 (0-25%) – – mean 2.8 2.9 figure 3. example before & after photos from 3d image analysis. show quantitative improvements in dimple depth and volume at 180 days treatment details • the most frequently used concomitant medication was dicloxicillin; however 38% of patients received no additional medications at the time of the procedure • average time for anesthesia delivery: 25 minutes pain rated on average as a 4.5/10. • average time for vacuum release: 21 minutes pain rated on average as a 1.7/10 table 4. treatment areas. most patients were treated on both the thighs and buttocks. subjects, n (%) average # of sites treated both 43 (81.1%) 11.9 buttocks 7 (13.2%) 16.4 thighs 3 (5.7%) 20.6 table 3. patient demographics characteristic subjects (n=53) mean age, y (range) 44.1 (23-61) mean baseline bmi (range) 22.3 (17.4-28.6) fitzpatrick skin type, n (%) i 0 (0) ii 18 (33.9) iii 23 (43.4) iv 10 (18.8) v 0 (0) vi 2 (3.8) ethnicity, n (%) caucasian 48 (90.5) aafrican american/black 1 (1.9) hispanic/latino 0 (0) asian 1 (1.9) native american/ alaskan native 3 (5.7) registry results • information gathered within the registry aligns with the pivotal study conducted previously2,3 • all patients experienced mild to moderate treatment effects, but no further treatment was required for any patient • quantitative image analysis directly supports the subjectand physician-assessed efficacy data by demonstrating objective improvements in dimple depth • results indicate this fdacleared long-lasting cellulite treatment that takes an average of under one hour is safe and effective in real-life clinical practice 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 22% 29% 33% 43% 40% 20% 9% 0% 0% physician rating subject rating 4% p a ti e n ts , % very much improved much improved any improvement patients: 91% physicians: 96% improved no change worse clinician and subject gais at day 180 figure 2. subject and physician gais scores at 180 days. mean physician rating was 2.05, corresponding to “much improved.” adverse events and expected treatment side effects • all subjects experienced some mild treatment effects, but no further treatment was required for any subject. • the majority of procedure-related adverse events resolved by 90 days • the most common effects were petechiae, bleeding and blanching, red spots from needle punctures, and fluid accumulation • mild to moderate • only 1 adverse event (induration) was reported • there were no serious adverse events reported conclusions table 5. treatment depth. the majority of releases were performed at the 6 mm depth. 6mm 10mm both buttocks (n=50) 30 (60%) 0 (0%) 20 (40%) thighs (n=46) 41 (89.1%) 1 (2.2%) 4 (8.7%) references: 1. cellfina system [instructions for use]. mesa, az: ulthera, inc.; 2016; 2. kaminer ms, et al. dermatol surg. 2015;41(3):336-347; 3. kaminer ms, et al. dermatol surg. 2017;43(10):1249-1262. cellfina® is a registered trademark of ulthera, inc. this study was sponsored by merz north america, inc. fc17postermerzgeronemusanobservationalstudy.pdf summary presented at the 42nd annual fall clinical dermatology conference | las vegas, nv | october 20–23, 2022 objectives to evaluate maintenance of response over three years among patients with moderate to severe plaque psoriasis who had an initial efficacy response after 16 weeks’ bimekizumab (bkz) treatment and entered the be bright open-label extension (ole), including those who received continuous bkz every 8 weeks (q8w) dosing in the maintenance period and the ole. introduction • loss of response to biologics over time is commonly observed in plaque psoriasis,1 it is therefore important to understand long-term efficacy of new therapies. • be bright (nct03598790) is an ongoing, multicentre, ole study assessing long-term safety, tolerability, and efficacy of bkz in patients with moderate to severe plaque psoriasis who completed one of three phase 3 feeder studies.2–4 • data reported previously indicated that response to bkz treatment is maintained over two years.5 materials and methods • all patients who completed one of the be sure (nct03412747), be vivid (nct03370133), and be ready (nct03410992) phase 3 studies were eligible to enrol in be bright and were assigned to treatment as shown in figure 1.2–4 • here, maintenance of psoriasis area and severity index (pasi) ≤2 among week 16 pasi ≤2 responders, maintenance of body surface area (bsa) ≤1% among week 16 bsa ≤1% responders, and maintenance of pasi 100 (100% improvement from baseline in pasi) and dermatology life quality index (dlqi) 0/1 among week 16 pasi 100 responders are reported through year 3 (ole week 96). • data are presented for all bkz-treated patients (bkz total) who entered the ole, and in the subset of patients who received bkz 320 mg every 4 weeks (q4w) through week 16 followed by continuous bkz 320 mg q8w (q4w/q8w). • data are reported using modified non-responder imputation (mnri), nri, and as the observed case (oc). – for mnri, patients who discontinued due to lack of efficacy were considered non-responders at subsequent timepoints; multiple imputation was used for all other missing data. results • 989 patients were randomized to bkz q4w at baseline in the feeder studies; 694 week 16 pasi ≤2 responders, 597 bsa ≤1% responders, and 503 week 16 pasi 100 responders entered the ole. baseline characteristics are presented in table 1. • 94.2%, 90.8%, and 82.0% of bkz-treated patients who achieved pasi ≤2, bsa ≤1%, and pasi 100, respectively, at week 16 maintained their response at year 3 (ole week 96) (figure 2; table 2). • dlqi 0/1 response rates in bkz-treated week 16 pasi 100 responders increased through the first year of bkz treatment, and were maintained through to the end of year 3 (ole week 96) in 88.0% of patients (figure 2; table 2). conclusions among week 16 responders, efficacy and health-related quality of life response rates were maintained through to three years’ bkz treatment, including among those who received bkz 320 mg q4w/q8w. bruce strober,1,2 yayoi tada,3 ulrich mrowietz,4 mark lebwohl,5 peter foley,6,7 richard g. langley,8 jonathan barker,9 maggie wang,10 veerle vanvoorden,11 balint szilagyi,12 valerie ciaravino,13 carle paul14 bimekizumab maintenance of response through three years in patients with moderate to severe plaque psoriasis who responded at week 16: results from the be bright open-label extension trial previously presented at eadv 2022 institutions: 1yale university, new haven, connecticut, usa; 2central connecticut dermatology research, cromwell, connecticut, usa; 3department of dermatology, teikyo university school of medicine, tokyo, japan; 4psoriasis center, department of dematology, university medical center schleswig-holstein, campus kiel, germany; 5icahn school of medicine at mount sinai, new york, new york, usa; 6the university of melbourne, st. vincent’s hospital melbourne, fitzroy, victoria, australia; 7probity medical research inc., skin health institute, carlton, victoria, australia; 8dalhousie university, halifax, nova scotia, canada; 9st. john’s institute of dermatology, king’s college london, london, uk; 10ucb pharma, raleigh, north carolina, usa; 11ucb pharma, brussels, belgium; 12ucb pharma, monheim, germany; 13ucb pharma, colombes, france; 14toulouse university and chu, toulouse, france. references: 1yiu zzn et al. br j dermatol 2020;183:294–302; 2warren rb et al. n engl j med 2021;385:130–41; 3reich k et al. lancet 2021;397:487–98; 4gordon kb et al. lancet 2021;397:475–86; 5strober b et al. presented at eadv 2021; p1317. author contributions: substantial contributions to study conception/design, or acquisition/analysis/interpretation of data: bst, yt, um, ml, pf, rgl, jb, mw, vv, bsz, vc, cp; drafting of the publication, or revising it critically for important intellectual content: bst, yt, um, ml, pf, rgl, jb, mw, vv, bsz, vc, cp; final approval of the publication: bst, yt, um, ml, pf, rgl, jb, mw, vv, bsz, vc, cp. author disclosures: bst: consultant (honoraria): abbvie, almirall, amgen, arcutis, arena, aristea therapeutics, asana, boehringer ingelheim, bristol myers squibb, connect biopharma, dermavant, eli lilly, epi health, evelo biosciences, immunic therapeutics, janssen, leo pharma, eli lilly, maruho, meiji seika pharma, mindera health, novartis, ono, pfizer, regeneron, sanofi-genzyme, sun pharma, ucb pharma, union therapeutics, ventyxbio, and vtv therapeutics; stock options: connect biopharma, mindera health; speaker: abbvie, eli lilly, janssen, regeneron, and sanofi-genzyme; scientific co-director (consulting fee): corevitas (formerly corrona) psoriasis registry; investigator: abbvie, cara therapeutics, corevitas psoriasis registry, dermavant, and novartis; editor-in-chief (honorarium): journal of psoriasis and psoriatic arthritis. yt: honoraria and/or grants from abbvie, boehringer ingelheim, bristol myers squibb, eisai, eli lilly, janssen, kyowa hakko kirin, leo pharma, maruho, mitsubishi tanabe pharma, sun pharma, taiho pharmaceutical, torii pharmaceutical, and ucb pharma. um: served as advisor and/or clinical study investigator for, and/or received honoraria and/or grants from abbvie, almirall, aristea therapeutics, boehringer ingelheim, celgene, dr. reddy’s laboratories, eli lilly, foamix, formycon, forward pharma, janssen, leo pharma, medac, novartis, phi-stone, pierre fabre, sanofi, and ucb pharma. ml: employee of mount sinai and receives research funds from abbvie, amgen, arcutis, avotres therapeutics, boehringer ingelheim, dermavant, eli lilly, incyte, janssen, ortho dermatologics, regeneron, and ucb pharma and is a consultant for aditum bio, almirall, altrubio, anaptysbio, arcutis, aristea therapeutics, arrive technologies, avotres therapeutics, biomx, boehringer ingelheim, bristol myers squibb, cara therapeutics, castle biosciences, corevitas, dermavant sciences, dr. reddy’s laboratories, evelo biosciences, evommune, facilitation of international dermatology education, forte biosciences, foundation for research and education in dermatology, helsinn therapeutics, hexima, leo pharma, meiji seika pharma, mindera health, pfizer, seanergy, and verrica. pf: grant support from abbvie, amgen, bristol myers squibb, celgene, eli lilly, janssen, leo pharma, merck, novartis, pfizer, sanofi, and sun pharma. he has served as an investigator for abbvie, akaal, amgen, arcutis, argenx, aslan, astrazeneca, boehringer ingelheim, botanix, bristol myers squibb, celgene, celtaxsys, csl, cutanea, dermira, eli lilly, evelo biosciences, galderma, geneseq, genentech, genesiscare, gsk, hexima, janssen, kymab, leo pharma, medimmune, merck, novartis, pfizer, regeneron, reistone, roche, sanofi, sun pharma, teva, ucb pharma, and valeant. he has served on advisory boards for abbvie, amgen, boehringer ingelheim, bristol myers squibb, celgene, eli lilly, galderma, gsk, janssen, leo pharma, mayne pharma, merck, novartis, pfizer, sanofi, sun pharma, ucb pharma, and valeant. he has served as a consultant for aslan, bristol myers squibb, eli lilly, galderma, genesiscare, janssen, leo pharma, mayne pharma, medimmune, novartis, pfizer, roche, ucb pharma, and wintermute. he has received travel grants from abbvie, eli lilly, galderma, janssen, leo pharma, merck, novartis, pfizer, roche, sun pharma, and sanofi, and has served as a speaker for or received honoraria from abbvie, amgen, celgene, eli lilly, galderma, gsk, janssen, leo pharma, merck, novartis, pfizer, roche, sanofi, sun pharma, and valeant. rgl: principal investigator for abbvie, amgen, boehringer ingelheim, celgene, eli lilly, leo pharma, merck, novartis, pfizer, and ucb pharma; served on scientific advisory boards for abbvie, amgen, boehringer ingelheim, celgene, eli lilly, leo pharma, merck, novartis, pfizer, ucb pharma; provided lectures for abbvie, amgen, celgene, eli lilly, leo pharma, merck, novartis, and pfizer. jb: within the past 5 years jb has attended advisory boards and/or received consultancy fees and/or spoken at sponsored symposia, and/or received grant funding from abbvie, almirall, amgen, anaptysbio, boehringer ingelheim, bristol myers squibb, celgene, eli lilly, janssen, leo pharma, novartis, pfizer, samsung, sienna, sun pharma, and ucb pharma. mw, vv, bsz: employees and shareholders of ucb pharma. vc: employee of employee and shareholder. cp: consulting fees and/or grants from abbvie, almirall, amgen, boehringer ingelheim, celgene, gsk, janssen cilag, leo pharma, eli lilly, novartis, pierre fabre, pfizer, sanofi regeneron, and ucb pharma. acknowledgements: this study was funded by ucb pharma. we thank the patients and their caregivers in addition to the investigators and their teams who contributed to this study. the authors acknowledge susanne wiegratz, msc, ucb pharma, monheim, germany for publication coordination, natalie nunez gomez, md, former employee of ucb pharma, monheim, germany, for critical review, alexa holland, msc, costello medical, manchester, uk for medical writing and editorial assistance and the design team at costello medical for graphic design assistance. all costs associated with development of this poster were funded by ucb pharma. figure 1 study design (included patients) figure 2 maintenance of efficacy in patients with a week 16 response who entered the ole (mnri) bkz: bimekizumab; bsa: body surface area; dlqi: dermatology quality of life index; mnri: modified non-responder imputation; nri: non-responder imputation; oc: observed case; ole: open-label extension; pasi: psoriasis area and severity index; pasi 100: 100% improvement from baseline in pasi; q4w: every 4 weeks; q8w: every 8 weeks; sd: standard deviation. table 1 baseline characteristics table 2 summary of efficacy outcomes (nri and oc) week 16 pasi ≤2 responders bkz total (n=694) week 16 bsa ≤1% responders bkz total (n=597) week 16 pasi 100 responders bkz total (n=503) age (years), mean ± sd 45.0 ± 13.3 44.9 ± 13.3 44.8 ± 13.2 male, n (%) 490 (70.6) 420 (70.4) 352 (70.0) weight (kg), mean ± sd 88.7 ± 20.5 88.4 ± 20.3 87.8 ± 19.3 duration of psoriasis (years), mean ± sd 18.4 ± 12.5 18.3 ± 12.6 18.0 ± 12.3 pasi, mean ± sd 21.2 ± 7.5 21.1 ± 7.4 21.3 ± 7.2 bsa (%), mean ± sd 27.0 ± 15.4 26.7 ± 15.2 26.7 ± 14.9 dlqi, mean ± sd 10.6 ± 6.3 10.7 ± 6.3 10.9 ± 6.4 any prior systemic therapy, n (%) 556 (80.1) 486 (81.4) 415 (82.5) prior biologic therapy, n(%) 278 (40.1) 245 (41.0) 210 (41.7) week 16 pasi ≤2 responders nri, n (%) oc, n/n (%)a nri, n (%) oc, n/n (%)a bkz total n=694 bkz 320 mg q4w/q8wb n=189 pasi ≤2 response year 1 (week 52) 663 (95.5) 663/678 (97.8) 186 (98.4) 186/188 (98.9) year 2 (ole week 48) 617 (88.9) 622/642 (96.9) 173 (91.5) 173/176 (98.3) year 3 (ole week 96) 586 (84.4) 592/612 (96.7) 165 (87.3) 165/166 (99.4) week 16 bsa ≤1% responders bkz total n=597 bkz 320 mg q4w/q8wb n=172 bsa ≤1% response year 1 (week 52) 555 (93.0) 555/586 (94.7) 165 (95.9) 165/171 (96.5) year 2 (ole week 48) 514 (86.1) 516/552 (93.5) 151 (87.8) 151/160 (94.4) year 3 (ole week 96) 490 (82.1) 491/526 (93.3) 146 (84.9) 146/151 (96.7) week 16 pasi 100 responders bkz total n=503 bkz 320 mg q4w/q8wb n=147 pasi 100 response year 1 (week 52) 447 (88.9) 447/495 (90.3) 137 (93.2) 137/146 (93.8) year 2 (ole week 48) 413 (82.1) 414/465 (89.0) 125 (85.0) 125/137 (91.2) year 3 (ole week 96) 383 (76.1) 384/447 (85.9) 113 (76.9) 113/130 (86.9) week 16 pasi 100 responders bkz total n=330 bkz 320 mg q4w/q8wb n=147 dlqi 0/1 responsec year 1 (week 56) 302 (91.5) 302/325 (92.9) 140 (95.2) 140/146 (95.9) year 2 (ole week 48) 280 (84.8) 281/307 (91.5) 123 (83.7) 123/137 (89.8) year 3 (ole week 96) 263 (79.7) 263/288 (91.3) 121 (82.3) 121/130 (93.1) data are reported for all patients who were treated continuously with bkz through the initial and maintenance periods, achieved the efficacy response of interest at week 16 and entered the ole. afor nri, patients in be ready who escaped to open-label bkz during the randomized withdrawal period are counted as non-responders from the point of escape and throughout all of be bright. for oc, data from the point of escape and through week 56 of be ready for these patients are considered as missing, and from the point of entry into be bright their data are presented as observed. as a result, the number of responders for oc may be higher than the number of responders for nri for the ole time points; bcontinuous q8w dosing in the maintenance period and the ole was only possible for patients who entered be bright from be sure or be ready; cdlqi was measured on a different schedule in be vivid compared with be sure and be ready; dlqi 0/1 data for patients enrolled in be vivid are therefore not included here, due to the lack of common visits at which dlqi was recorded. abe sure and be ready had a duration of 56 weeks and be vivid had a duration of 52 weeks; bat ole week 24, patients receiving bkz q4w who achieved pasi 90 could switch to receive bkz q8w at the discretion of the investigator; cat ole week 48, or at the next scheduled clinic visit, all patients were re-assigned to bkz q8w, following protocol amendment. week 16 responses are shown for all patients randomized to bkz 320 mg q4w in the initial treatment period. due to the differing lengths of feeder studies, week 56 data for pasi ≤2, bsa ≤1% and pasi 100 responses in be sure and be ready are not presented in these pooled analyzes. adlqi was measured on a different schedule in be vivid compared with be sure and be ready; dlqi 0/1 data for patients enrolled in be vivid are therefore not included, due to the lack of common visits at which dlqi was recorded. a) pasi ≤2 in week 16 pasi ≤2 responders c) pasi 100 in week 16 pasi 100 responders b) bsa ≤1% in week 16 bsa ≤1% responders d) dlqi 0/1 in week 16 pasi 100 respondersa maintenance of week 16 responses at year 3 (ole week 96) bkz provided long-term maintenance of efficacy and health-related quality of life benefit over three years in patients with moderate to severe plaque psoriasis who achieved an initial response at week 16. pasi ≤2 in pasi ≤2 responders (n=694) bsa ≤1% in bsa ≤1% responders (n=597) bkz total (mnri) pasi 100 in pasi 100 responders (n=503) dlqi 0/1 in pasi 100 responders (n=330) 94.2% 90.8% 82.0% 88.0% be sure, be vivid and be ready (pooled, double-blinded) be bright (open-label extension) screening maintenance period open-label treatment period initial treatment period bkz 320 mg q4w bkz 320 mg q4w <pasi 90 <pasi 90 ≥pasi 90 ≥pasi 90 4:1 bkz 320 mg q8w n=989 all bkzrandomised patients bkz 320 mg q4w bkz 320 mg q4w bkz 320 mg q8w bkz 320 mg q8w ≥pasi 90 investigator discretion ≥pasi 90 investigator discretion baseline 2–5 weeks week 16 response assessment ole week 0 (week 52/56)a ole week 24b (week 76/80)a ole week 48c (week 100/104)a ole week 96 (week 148/152)a ole week 48 or next scheduled visit ole week 48 or next scheduled visit proportion of week 16 pasi ≤2 responders with pasi ≤2 response (%) 80 60 40 20 0 100 2016 24 28 32 36 404448 52 4 8 12 16 20 24 28 32 36 4044 4852 56 606468 72 76 8084 8892 96 98.9% 96.5% 97.4% 95.4% 96.8% 94.2% week ole week bkz total (mnri; n=694) bkz 320 mg q4w/q8w (mnri; n=189) double-blinded treatment open-label extension pasi ≤2 response rate at week 16 in bkz-randomized patients (n=989) bkz 320 mg q4w (nri; initial treatment period) 87.8% 80 60 40 20 0 100 double-blinded treatment open-label extension proportion of week 16 pasi 100 responders with pasi 100 response (%) bkz total (mnri; n=503) bkz 320 mg q4w/q8w (mnri; n=147) 93.6% 89.3% 89.1% 86.0% 84.4% 82.0% pasi 100 response rate at week 16 in bkz-randomized patients (n=989) bkz 320 mg q4w (nri; initial treatment period) 62.7% 2016 24 28 32 36 404448 52 4 8 12 16 20 24 28 32 36 4044 4852 56 606468 72 76 8084 8892 96 week ole week 80 60 40 20 0 100 double-blinded treatment 92.8% 91.7% 94.6% 90.8% open-label extension 96.5% 94.0% proportion of week 16 bsa ≤1% responders with bsa ≤1% response (%) bkz total (mnri; n=597) bkz 320 mg q4w/q8w (mnri; n=172) bsa ≤1% response rate at week 16 in bkz-randomized patients (n=989) bkz 320 mg q4w (nri; initial treatment period) 74.9% 2016 24 28 32 36 404448 52 4 8 12 16 20 24 28 32 36 4044 4852 56 606468 72 76 8084 8892 96 week ole week pasi 100 response rate at week 16 in bkz-randomized patients (n=989) bkz 320 mg q4w (nri; initial treatment period) 62.7% proportion of week 16 pasi 100 responders with dlqi 0/1 response (%) bkz total (mnri; n=330) bkz 320 mg q4w/q8w (mnri; n=147) 80 60 40 20 0 100 double-blinded treatment open-label extension 95.8% 92.0% 89.8% 90.4% 92.5% 88.0% 2016 24 28 32 36404448 52 4 8 12 16 20 24 28 32 36404448 52 56606468 72 76 8084889296 week ole week 56